FN Thomson Reuters Web of Science™ VR 1.0 PT J AU PERICAKVANCE, MA BALE, AE HAINES, JL KWIATKOWSKI, DJ PILZ, A SLAUGENHAUPT, S WHITE, JA EDWARDS, JH MARCHUK, D OLOPADE, OI ATTWOOD, J POVEY, S AF PERICAKVANCE, MA BALE, AE HAINES, JL KWIATKOWSKI, DJ PILZ, A SLAUGENHAUPT, S WHITE, JA EDWARDS, JH MARCHUK, D OLOPADE, OI ATTWOOD, J POVEY, S TI REPORT ON THE 4TH INTERNATIONAL WORKSHOP ON CHROMOSOME-9 HELD AT WILLIAMSBURG, VIRGINIA, USA, APRIL 23-25, 1995 SO ANNALS OF HUMAN GENETICS LA English DT Article ID NONKETOTIC HYPERGLYCINEMIA; GENE AB The Fourth International Workshop on Chromosome 9 was a highly successful endeavor in terms of the growth of the map, both genetic and physical, the amount of data entered into GDB, and the continued comradeship in the sharing of data and resources that was exemplified. SIGMA remained a stable and valuable part of the chromosome 9 mapping effort. A new subsection outlining the morbid anatomy of chromosome 9 was included. Finally, specific goals were set for the community to aim for over the upcoming months. These included extending the information about the ease of use of genetic markers, and coordinating across numerous groups the meiotic breakpoint mapping of many microsatellite markers. Workshop files are available by anonymous ftp from ftp.gene.ucl.ac.uk (128.40.82.1) in the subdirectory /pub/c9workshop/1995, or by using a World Wide Web browser (such as Mosaic or Netscape) via the Chromosome 9 Home Page (at the URL http://www.gene/ucl.ac.uk/chr9home.html). C1 YALE UNIV, SCH MED, SHM I321, DEPT GENET, NEW HAVEN, CT 06520 USA. MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BOSTON, MA 02129 USA. BRIGHAM & WOMENS HOSP, DIV EXPTL MED, BOSTON, MA 02115 USA. UCL, GALTON LAB, DEPT GENET & BIOMETRY, LONDON NW1 2HE, ENGLAND. UCL, GALTON LAB, MRC, HUMAN BIOCHEM GENET UNIT, LONDON NW1 2HE, ENGLAND. UNIV OXFORD, DEPT BIOCHEM, GENET LAB, OXFORD OX1 3QU, ENGLAND. DUKE UNIV, MED CTR, DEPT GENET, CLIN & RES LABS 265, DURHAM, NC 27710 USA. UNIV CHICAGO, MED CTR, CHICAGO, IL 60637 USA. RP PERICAKVANCE, MA (reprint author), DUKE UNIV, MED CTR, DIV NEUROL, BOX 2900, DURHAM, NC 27710 USA. RI Haines, Jonathan/C-3374-2012 NR 41 TC 26 Z9 26 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD OCT PY 1995 VL 59 BP 347 EP 365 DI 10.1111/j.1469-1809.1995.tb00756.x PN 4 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA TF786 UT WOS:A1995TF78600001 ER PT J AU ZEITELS, SM KIRCHNER, JA AF ZEITELS, SM KIRCHNER, JA TI HYOEPIGLOTTIC LIGAMENT IN SUPRAGLOTTIC CANCER SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE CANCER; EPIGLOTTIS; HYOEPIGLOTTIC LIGAMENT; LARYNGECTOMY; LARYNX; PARAGLOTTIC SPACE; PREEPIGLOTTIC SPACE; SUPRAGLOTTIS AB The hyoepiglottic ligament (HL) is a connective tissue structure that serves as the roof of both the paraglottic and the preepiglottic spaces and thereby anatomically separates the supraglottic larynx from the tongue base. Whole mount serially sectioned larynges with supraglottic cancer were reviewed to help clarify cephalad spread of cancer in this region. The whole mount slides were analyzed from 70 laryngectomy specimens that were resected for supraglottic cancer. The HL was breached by cancer in 13 specimens, and all of these displayed clinical and histopathologic invasion of the preepiglottic and paraglottic spaces. Invasion of the suprahyoid epiglottis was noted in 9 specimens, and invasion of the aryepiglottic fold in 4. There were no instances in which cancer escaped from the deep compartments of the supraglottic larynx to the tongue base without synchronous erosion of the suprahyoid epiglottis (insertion of the medial HL) or the pharyngoepiglottic fold (lateral HL). The HL is a resilient connective tissue barrier to the spread of cancer from the supraglottis to the tongue base. This investigation reinforced the concept that, typically, the HL acts as a deep cephalad surgical boundary in resecting supraglottic cancer that 1) is confined to the laryngeal membranes and 2) does not clinically invade the suprahyoid epiglottis. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT SURG,OTOLARYNGOL SECT,NEW HAVEN,CT 06510. RP ZEITELS, SM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [2-R01-CA 22101-11] NR 20 TC 3 Z9 3 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 1995 VL 104 IS 10 BP 770 EP 775 PN 1 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA RZ461 UT WOS:A1995RZ46100004 PM 7574253 ER PT J AU TANABE, KK STAMENKOVIC, I CUTLER, M TAKAHASHI, K AF TANABE, KK STAMENKOVIC, I CUTLER, M TAKAHASHI, K TI RESTORATION OF CD44H EXPRESSION IN COLON CARCINOMAS REDUCES TUMORIGENICITY SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 115th Annual Meeting of the American-Surgical-Association CY APR 06-08, 1995 CL CHICAGO, IL SP Amer Surg Assoc ID LYMPHOCYTE HOMING RECEPTOR; CELL-SURFACE GLYCOPROTEIN; FIBRONECTIN RECEPTOR; ADHESION MOLECULES; RECOGNITION; VARIANTS; CANCER; HYALURONATE; EXONS; BINDING AB Objective The functional consequences of reintroduction of the CD44H cell adhe Background CD44 is a cell surface adhesion molecule that is normally present in numerous isoforms as a result of messenger RNA alternative splicing. Individual CD44 isoforms differ in their ability to enhance tumorigenic or metastatic potential when overexpressed on tumor cells. Reverse transcriptase-polymerase chain reaction analysis demonstrates that CD44H is down-regulated during transformation of normal colon mucosa to carcinoma. The functional consequences of CD44H down-regulation in colon carcinomas has not been clarified. Methods Tumor cell lines and fresh tissue specimens were examined for CD44 expression by Western blot analysis. CD44H cDNA and site-directed mutants of CD44H cDNA were transfected into colon carcinoma cells. Stable transfectants were examined for adhesion to hyaluronate, in vitro growth, and in vivo growth. Results CD44H expression was nearly undetectable in primary colon carcinomas and colon carcinoma cell lines. In contrast, normal mucosa expressed high levels of CD44H. When CD44H was reintroduced into colon carcinoma cells, their in vitro and in vivo growth was significantly reduced. This CD44H-mediated growth rate reduction required an intact cytoplasmic domain. Conclusions Transformation of normal mucosa to colon carcinoma is associated with a down-regulation of CD44H, which consequently may enhance the growth rate and tumorigenicity. C1 MASSACHUSETTS GEN HOSP, DEPT SURG, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. RP TANABE, KK (reprint author), MASSACHUSETTS GEN HOSP, DIV SURG ONCOL, COX 626, BOSTON, MA 02114 USA. FU NCI NIH HHS [CA64454, CA55735]; NIDDK NIH HHS [DK 43351] NR 52 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 1995 VL 222 IS 4 BP 493 EP 503 PG 11 WC Surgery SC Surgery GA RZ273 UT WOS:A1995RZ27300007 PM 7574929 ER PT J AU GRAYBILL, JR NAJVAR, LK HOLMBERG, JD CORREA, A LUTHER, MF AF GRAYBILL, JR NAJVAR, LK HOLMBERG, JD CORREA, A LUTHER, MF TI FLUCONAZOLE TREATMENT OF CANDIDA-ALBICANS INFECTION IN MICE - DOES IN-VITRO SUSCEPTIBILITY PREDICT IN-VIVO RESPONSE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FUNGAL-INFECTIONS; ORAL CANDIDIASIS; TRIAL; EPIDEMIOLOGY; RESISTANCE; MORTALITY; GLABRATA; FUNGEMIA AB A series of fluconazole-susceptible and-fluconazole resistant Candida albicans fungal isolates mere used to infect mice intravenously. Mice were treated with varying doses of fluconazole beginning one day after infection. For all of the 6 fluconazole-susceptible isolates, fluconazole was highly effective at <0.25 mg/kg of body weight twice daily. By contrast, fluconazole was less effective in at least 6 of 10 fluconazole-resistant isolates and was ineffective at greater than or equal to 40 mg/kg twice daily in 4 fluconazole-resistant isolates. Although the correlation is not precise, in vitro susceptibility testing of C. albicans can predict in vivo response to fluconazole. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. RP GRAYBILL, JR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DIV INFECT DIS 111F,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 24 TC 19 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1995 VL 39 IS 10 BP 2197 EP 2200 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RX469 UT WOS:A1995RX46900006 PM 8619566 ER PT J AU ATKINSON, BA BOCANEGRA, R GRAYBILL, JR AF ATKINSON, BA BOCANEGRA, R GRAYBILL, JR TI TREATMENT OF MYCOBACTERIUM-HAEMOPHILUM INFECTION IN A MURINE MODEL WITH CLARITHROMYCIN, RIFABUTIN, AND CIPROFLOXACIN SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HEMOPHILUM; AIDS AB An animal model of disseminated Mycobacterium haemophilum infection was utilized to compare treatment with azithromycin, ciprofloxacin, rifabutin, and the combination of clarithromycin with rifabutin. Following subcutaneous challenge with M. haemophilum, local and disseminated infection occurred only in immunosuppressed mice. For disseminated infection, ciprofloxacin was relatively ineffective therapy. Clarithromycin and rifabutin alone significantly reduced the tissue burden in the spleen after 4 weeks of therapy. Combination therapy with rifabutin and clarithromycin was superior to 4 weeks of treatment with the individual agents. When immunosuppressed mice were treated for 20 weeks with the combination of rifabutin and clarithromycin, the tissue burden remained reduced in the spleen at 1 month following the completion of therapy. Combined rifabutin and clarithromycin provide effective treatment for M. haemophilum in this model. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 21 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1995 VL 39 IS 10 BP 2316 EP 2319 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA RX469 UT WOS:A1995RX46900028 PM 8619588 ER PT J AU BOUFFARD, D TAYLOR, CR MIHM, MC BYERS, HR AF BOUFFARD, D TAYLOR, CR MIHM, MC BYERS, HR TI LONG-STANDING VERRUCOUS LESION SO ARCHIVES OF DERMATOLOGY LA English DT Note ID CHROMOMYCOSIS; CHROMOBLASTOMYCOSIS C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP BOUFFARD, D (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 1995 VL 131 IS 10 BP 1196 EP & PG 0 WC Dermatology SC Dermatology GA RZ277 UT WOS:A1995RZ27700017 ER PT J AU GRANSTEIN, RD AF GRANSTEIN, RD TI EVIDENCE THAT SUNSCREENS PREVENT UV RADIATION-INDUCED IMMUNOSUPPRESSION IN HUMANS - SUNSCREENS HAVE THEIR DAY IN THE SUN SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID TUMOR-ANTIGEN PRESENTATION; NECROSIS-FACTOR-ALPHA; INDUCED SKIN TUMORS; CONTACT HYPERSENSITIVITY; ULTRAVIOLET-RADIATION; EPIDERMAL-CELLS; INDUCED SUPPRESSION; PRESENTING CELLS; IRRADIATED MICE; INDUCTION C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP GRANSTEIN, RD (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114, USA. NR 44 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD OCT PY 1995 VL 131 IS 10 BP 1201 EP 1204 PG 4 WC Dermatology SC Dermatology GA RZ277 UT WOS:A1995RZ27700020 PM 7574842 ER PT J AU TSAI, GC PASSANI, LA SLUSHER, BS CARTER, R BAER, L KLEINMAN, JE COYLE, JT AF TSAI, GC PASSANI, LA SLUSHER, BS CARTER, R BAER, L KLEINMAN, JE COYLE, JT TI ABNORMAL EXCITATORY NEUROTRANSMITTER METABOLISM IN SCHIZOPHRENIC BRAINS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PIG CEREBELLAR SLICES; N-ACETYLASPARTYLGLUTAMATE; AMINO-ACIDS; MK-801 BINDING; HUNTINGTONS-DISEASE; PURKINJE-CELLS; KAINIC ACID; RAT-BRAIN; GLUTAMATE; RECEPTOR AB Background: Schizophrenia has been hypothesized to be caused by a hypofunction of glutamatergic neurons. Findings of reduced concentrations of glutamate in the cerebrospinal fluid of patients with schizophrenia and the ability of glutamate-receptor antagonists to cause psychotic symptoms lend support to this hypothesis. N-acetylaspartylglutamate (NAAG), a neuropeptide that is highly concentrated in glutamatergic neurons, antagonizes the effects of glutamate at N-methyl-D-aspartate receptors. Moreover, NAAG is cleaved to glutamate and N-acetylaspartate by a specific peptidase, N-acetyl-alpha-linked acidic dipeptidase (NAALADase). To test the glutamatergic hypothesis of schizophrenia, we studied the NAAG-related glutamatergic variables in postmortem brains from patients with schizophrenia, neuroleptic-treated controls, and normal individuals, with particular emphasis on the prefrontal cortex and hippocampus. Method: Different regions of frozen brain tissue from three different groups (patients with schizophrenia, neuroleptic-treated controls, and normal controls) were assayed to determine levels of NAAG, N-acetylaspartate, NAALADase, and several amino acids, including aspartate and glutamate. Results: Our study demonstrates alterations in brain levels of aspartate, glutamate, and NAAG and in NAALADase activity. Levels of NAAG were increased and NAALADase activity and glutamate levels were decreased in the schizophrenic brains. Notably, the changes in NAAG level and NAALADase activity in schizophrenic brains were more selective than those for aspartate and glutamate. In neuroleptic-treated control brains, levels of aspartate, glutamate, and glycine were found to be increased. Conclusions: The changes in levels of aspartate, glutamate, NAAG, and NAALADase are prominent in the prefrontal and hippocampal regions, where previous neuropathological studies of schizophrenic brains demonstrate consistent changes. These findings support the hypothesis that schizophrenia results from a hypofunction of certain glutamatergic neuronal systems. They also suggest that the therapeutic efficacy of neuroleptics may be related to increased glutamatergic activity. C1 HARVARD UNIV,SCH MED,MOLEC & DEV NEUROSCI LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. FU NIMH NIH HHS [R01 MH51290-01] NR 46 TC 323 Z9 329 U1 4 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 1995 VL 52 IS 10 BP 829 EP 836 PG 8 WC Psychiatry SC Psychiatry GA RY979 UT WOS:A1995RY97900005 PM 7575102 ER PT J AU SANO, M DEVANAND, DP RICHARDS, M MILLER, LW MARDER, K BELL, K DOONEIEF, G BYLSMA, FW LAFLECHE, G ALBERT, M FOLSTEIN, M STERN, Y AF SANO, M DEVANAND, DP RICHARDS, M MILLER, LW MARDER, K BELL, K DOONEIEF, G BYLSMA, FW LAFLECHE, G ALBERT, M FOLSTEIN, M STERN, Y TI A STANDARDIZED TECHNIQUE FOR ESTABLISHING ONSET AND DURATION OF SYMPTOMS OF ALZHEIMERS-DISEASE SO ARCHIVES OF NEUROLOGY LA English DT Article ID MEMORY COMPLAINTS; RELIABILITY; PREDICTORS; RELATIVES AB Objectives: To develop an informant-based semistructured interview to determine the onset and duration of symptoms of Alzheimer's disease, and to use this instrument with informants to characterize a cohort of mildly impaired patients with Alzheimer's disease. Design: In study 1, interrater and interinformant reliability was examined for the date of onset and the order of appearance for specific symptoms that were elicited by the semistructured onset interview. In study 2, the instrument was used to characterize disease onset in a cohort of patients with Alzheimer's disease who were participating in a large multicenter study. Subjects: Informants of patients with Alzheimer's disease. Results: In study 1, interrater reliability for duration of illness was excellent (intraclass correlation coefficient = .99, P < .001), and interinformant reliability was good (intraclass correlation coefficient = .86, P < .001). Agreement for the presence of a given symptom was highest for those that were most commonly reported leg, memory and performance difficulty). In study 2, 89% of the cohort had memory problems, and 63.9% had performance difficulties as the first or second symptom. Depression and language problems were less commonly reported. Psychosis and behavioral disturbances were rarely reported as the first problem. Conclusion: This instrument provides a reliable procedure for standardizing the estimation of duration of illness based on retrospective report. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT PSYCHIAT,NEW YORK,NY 10032. NEW YORK STATE PSYCHIAT INST & HOSP,CTR MEMORY DISORDERS,NEW YORK,NY. CTR ALZHEIMERS DIS RES,NEW YORK,NY. JOHNS HOPKINS UNIV,DEPT PSYCHIAT,BALTIMORE,MD. JOHNS HOPKINS UNIV,DEPT BEHAV SCI,BALTIMORE,MD. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. RP SANO, M (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,SERGIEVSKY CTR,BOX 16,630 W 168TH ST,NEW YORK,NY 10032, USA. FU NIA NIH HHS [AG-07370, AG-07232, AG-08702] NR 19 TC 39 Z9 39 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 1995 VL 52 IS 10 BP 961 EP 966 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA RY609 UT WOS:A1995RY60900005 PM 7575223 ER PT J AU MANGIONE, CM ORAV, EJ LAWRENCE, MG PHILLIPS, RS SEDDON, JM GOLDMAN, L AF MANGIONE, CM ORAV, EJ LAWRENCE, MG PHILLIPS, RS SEDDON, JM GOLDMAN, L TI PREDICTION OF VISUAL FUNCTION AFTER CATARACT-SURGERY - A PROSPECTIVELY VALIDATED MODEL SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID LENS IMPLANTATION; VISION; ACUITY AB Objective: To develop a model to predict visual functional improvement after cataract extraction with intraocular lens implantation based on preoperative data. Design: A prospective study with serial evaluations of visual function preoperatively and at 3 and 12 months after surgery. Setting: The General Eye Service of the Massachusetts Eye and Ear Infirmary, Boston, Mass, and 33 ophthalmology practices in Boston. Patients: Patients (N=426; ages, greater than or equal to 65 years) who were undergoing cataract surgery. Methods: Twelve-month improvement in visual function was measured by using the Activities of Daily Vision Scale (ADVS). Ordinal logistic regression was used to identify correlates of improved ADVS scores in 281 patients (derivative set). Potential factors included the preoperative visual acuity, preoperative ADVS score, four chronic ocular diseases, eight medical conditions, and demographic characteristics. Five predictors were identified and used to construct a prediction rule. The accuracy of the prediction rule was evaluated in an independent group of 145 patients (validation set). Results: Postoperatively, 40% of the 281 patients in the derivative set had substantial improvement in their ADVS scores, and 53 (19%) had some improvement. Predictors of improvement included younger age (P<.001), a poorer preoperative ADVS score (P<.001), posterior subcapsular cataract (P=.09), and absence of age-related macular degeneration (P=.07) and/or diabetes (P=.006). When applied to the independent sample of 145 patients, these five characteristics classified the patients into three groups in which the probabilities of substantial improvement were 85%, 34%, and 3%, thus verifying the discriminatory power of the prediction rule. Conclusions: Preoperative data can identify patients who are likely to have improvements in visual function after cataract surgery. Such findings may be useful in the selection of patients for this high-volume procedure. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV CLIN EPIDEMIOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,EPIDEMIOL UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,GEN EYE SERV,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. FU AHRQ HHS [FS32 HS00048-01]; NIA NIH HHS [1K08-AG00605] NR 20 TC 55 Z9 56 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 1995 VL 113 IS 10 BP 1305 EP 1311 PG 7 WC Ophthalmology SC Ophthalmology GA RY945 UT WOS:A1995RY94500029 PM 7575265 ER PT J AU PARK, SS SAMIY, N RUOFF, K DAMICO, DJ BAKER, AS AF PARK, SS SAMIY, N RUOFF, K DAMICO, DJ BAKER, AS TI EFFECT OF INTRAVITREAL DEXAMETHASONE IN TREATMENT OF PNEUMOCOCCAL ENDOPHTHALMITIS IN RABBITS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID STAPHYLOCOCCUS-EPIDERMIDIS ENDOPHTHALMITIS; BACTERIAL-MENINGITIS; CEREBROSPINAL-FLUID; CELL-WALL; CORTICOSTEROIDS; INFLAMMATION; INJECTION; INDUCTION; TOXICITY; THERAPY AB Purpose: To investigate whether corticosteroid therapy would decrease the inflammation and tissue damage associated with pneumococcal endophthalmitis. Methods: Albino rabbits were injected intravitreally with 1000 live organisms of Streptococcus pneumoniae and randomized after 24 hours to treatment with intravitreal vancomycin hydrochloride alone (n=10), combination intravitreal vancomycin and intravitreal dexamethasone (n=10), or no treatment (n=10). After 2 weeks, the eyes were examined clinically and enucleated for histopathologic examination. Results: Eyes treated with vancomycin and dexamethasone had significantly less intraocular inflammation and more preservation of retinal tissue than untreated eyes or eyes treated with vancomycin alone (P<.05, Fisher's exact test). Untreated and vancomycin-treated eyes were indistinguishable on clinical and histologic examination. Marked anterior and posterior segment inflammation with total retinal necrosis was noted in eyes from both groups. Conclusion: Intravitreal corticosteroid therapy may play an important role in minimizing the inflammation and tissue damage associated with pneumococcal endophthalmitis. C1 MASSACHUSETTS EYE & EAR INFIRM,INFECT DIS SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CLIN MICROBIOL LAB,BOSTON,MA 02114. RP PARK, SS (reprint author), UNIV TEXAS,SW MED CTR,DEPT OPHTHALMOL,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. NR 27 TC 46 Z9 49 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 1995 VL 113 IS 10 BP 1324 EP 1329 PG 6 WC Ophthalmology SC Ophthalmology GA RY945 UT WOS:A1995RY94500032 PM 7575268 ER PT J AU DAVID, SK CHENEY, ML AF DAVID, SK CHENEY, ML TI ANATOMIC STUDY OF THE TEMPOROPARIETAL FASCIAL FLAP SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID RECONSTRUCTION; GRAFTS AB Objective: To clarify the neurovascular relationships in the temporoparietal fascial flap and to access its possible use as a sensate free of a pedicled flap. Design: Anatomic dissections (gross) and examinations (histologic) were performed on 10 fresh cadaver heads. Setting: Academic tertiary care facility, Boston, Mass. Main Outcome Measures: To determine the relationship of the sensory innervation (the auriculotemporal nerve) to the vascular supply (the superficial temporal artery) of the temporoparietal fascial flap, in addition to determining safe incisions and the level of flap elevation that will preserve the sensory supply to the flap. Results: There is a consistent relationship of the auriculotemporal nerve to the superficial temporal artery allowing for auriculotemporal nerve preservation with standard flap elevation techniques and easy nerve identification in this cadaveric study. Conclusion: A clear understanding of the anatomic pattern allows for the potential creation of a sensate fascial flap or vascularized nerve graft that would add a potential additional dimension to this fascial flap. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,DIV FACIAL PLAST & RECONSTRUCT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. NR 20 TC 27 Z9 27 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 1995 VL 121 IS 10 BP 1153 EP 1156 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA RY831 UT WOS:A1995RY83100010 PM 7546583 ER PT J AU BLOCH, DB SANMARTIN, JE RAUCH, SD MOSCICKI, RA BLOCH, KJ AF BLOCH, DB SANMARTIN, JE RAUCH, SD MOSCICKI, RA BLOCH, KJ TI SERUM ANTIBODIES TO HEAT-SHOCK-PROTEIN-70 IN SENSORINEURAL HEARING-LOSS SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID STRESS PROTEINS; AUTOANTIBODIES; DISEASE; COCHLEA AB Objective: To identify the 68-kd target of antibody in serum samples from patients with idiopathic, progressive, bilateral sensorineural hearing loss. Design: To purify target protein from renal extracts using gel filtration, ion-exchange chromatography, and polyacrylamide gel electrophoresis and to transfer to nitrocellulose membranes. The purified protein was digested with trypsin, and peptide fragments were separated by high-pressure liquid chromatography. Results: One fraction obtained by high-performance liquid chromatography contained a peptide of 2776 molecular weight. The sequence of a stretch of 22 amino acids within this peptide was identical to that of amino acids 424 through 445 of heat shock protein 70 (HSP70). On Western blotting, monoclonal antibody directed against HSP70 (but capable of recognizing both constitutive HSP70 [HSC70] and stress-inducible HSP70) reacted with the purified 68-kd protein. We compared the reactivity of serum samples from six patients with idiopathic, progressive, bilateral sensorineural hearing loss, as well as monoclonal antibody to HSC70, and monoclonal antibody to HSP70 with renal extract. The pattern obtained suggested that patient antibodies are preferentially directed-at HSP70. Conclusion: The target of antibody in serum samples from patients with idiopathic, progressive, bilateral sensorineural hearing loss is HSP70. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN MED SERV,ALLERGY & CLIN IMMUNOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN MED SERV,ARTHRITIS UNIT,BOSTON,MA 02114. FU NCI NIH HHS [PC 00824]; NIAMS NIH HHS [AR 01866] NR 23 TC 58 Z9 59 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 1995 VL 121 IS 10 BP 1167 EP 1171 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA RY831 UT WOS:A1995RY83100013 PM 7546586 ER PT J AU LAPOSATA, M LEWANDROWSKI, KB AF LAPOSATA, M LEWANDROWSKI, KB TI NEAR PATIENT BLOOD-GLUCOSE MONITORING SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article AB This report describes the quality control and quality assurance programs for bedside glucometry at our institution, From our 3-year experience, a regular schedule of inspections is necessary for maintenance of high-quality bedside glucose testing. The most common violation of quality control/quality assurance in bedside glucometry in our institution was the failure to perform regular proficiency testing, in which one random patient's bedside capillary blood glucose value during each inspection period was compared to his or her venous plasma or serum glucose value obtained from the central laboratory. Failure to perform instrument maintenance and document operator certification were the next most common violations of quality control/quality assurance in our bedside glucometry program. Regarding the cost analysis for bedside glucometry, we conclude that bedside glucose testing is not inherently more expensive than testing performed within the clinical laboratory. The increased cost of bedside glucometry over laboratory testing can be significantly minimized by involvement of a limited number of health care workers and performance of bedside glucometry only on clinical units where testing is required more than five times per day. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP LAPOSATA, M (reprint author), MASSACHUSETTS GEN HOSP,DIV CLIN LABS,ROOM 235 GRAY BLDG,32 FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 1995 VL 119 IS 10 BP 926 EP 928 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA RZ609 UT WOS:A1995RZ60900016 PM 7487393 ER PT J AU TOUSSAINT, JF SOUTHERN, JF FUSTER, V KANTOR, HL AF TOUSSAINT, JF SOUTHERN, JF FUSTER, V KANTOR, HL TI T-2-WEIGHTED CONTRAST FOR NMR CHARACTERIZATION OF HUMAN ATHEROSCLEROSIS SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE NMRIMAGING; ATHEROSCLEROSIS; HUMANS T2 RELAXATION; ATHEROMATOUS PLAQUE; COLLAGENOUS CAP CALCIFICATION; LIPIDS ID HUMAN ATHEROMA; CIRCUMFERENTIAL STRESS; LIPID DEPOSITS; PLAQUES; DENSITY; INVIVO; TISSUE; QUANTIFICATION; SPECTROSCOPY; PROGRESSION AB We sought to determine whether H-1 NMR images without chemical-shift selection can adequately characterize the components of human atheromatous arteries. NMR, as a nondestructive, biochemical imaging tool, has the potential to identify lipids in atherosclerotic plaques but has not yet produced detailed images of atheroma components. Using H-1 NMR spectroscopy at 9.4 T, we examined microdissected components of diseased and normal arteries to determine water relaxation constants (T1 and T2) as well as the relative content of mobile lipid. Relaxation times were also measured at 1.5 and 4.7 T. Sections of arteries with atherosclerotic lesions of graded severity were imaged at 1.5 and 9.4 T. The contrast-to-noise ratio (CNR) was used to assess lesion conspicuity. In the atheromatous core, the water NMR signal predominates over that of lipid (lipid-to-water ratio, 0.11). At 9.4 T, T2 is 20.2 ms for the atheromatous core, 30.1 ms for the collagenous cap, and 29.5 ms for normal media. This results in a high CNR on T2-weighted (T2w) images for atheromatous core compared with the collagenous cap and normal media. A similar contrast was measured at lower field strength. Calcifications do not generate appreciable signal due to their low water content but can be detected on T1-weighted (T1w) images. The water T2 contrast allows discrimination of the atheromatous lipid core from collagenous regions. The combination of T1w and T2w sequences permits in vitro identification of the atheromatous core, collagenous cap, calcifications, media, adventitia, and perivascular fat. The discrimination of collagen fibers that overlie lipid deposits permits study of plaque protection and stability at all field strengths and may provide the basis for in vivo microscopy of human atherosclerosis. RP TOUSSAINT, JF (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,GRJ1410,32 FRUIT ST,BOSTON,MA 02114, USA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 FU NHLBI NIH HHS [R01-HL39371] NR 48 TC 165 Z9 167 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscl. Thromb. Vasc. Biol. PD OCT PY 1995 VL 15 IS 10 BP 1533 EP 1542 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA RZ865 UT WOS:A1995RZ86500001 PM 7583524 ER PT J AU NANAGARA, R LI, F BEUTLER, A HUDSON, A SCHUMACHER, HR AF NANAGARA, R LI, F BEUTLER, A HUDSON, A SCHUMACHER, HR TI ALTERATION OF CHLAMYDIA-TRACHOMATIS BIOLOGIC BEHAVIOR IN SYNOVIAL MEMBRANES - SUPPRESSION OF SURFACE-ANTIGEN PRODUCTION IN REACTIVE ARTHRITIS AND REITERS-SYNDROME SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; MONOCLONAL-ANTIBODIES; ELECTRON-MICROSCOPY; HUMAN-MONOCYTES; RIBOSOMAL-RNA; PROTEIN; INFECTION; LIPOPOLYSACCHARIDE; MACROPHAGES; INTERFERON AB Objective. To investigate the biologic state of Chlamydia and its surface antigen expression in the synovial membranes of patients with Chlamydia-associated reactive arthritis/Reiter's syndrome (ReA/RS). Methods, Expression of chlamydial lipopolysaccharide (LPS), major outer membrane protein (MOMP), and elementary body (EB) antigens was studied by gold labeling immunoelectron microscopy on 6 synovial membrane and 2 synovial fluid (SF) pellet samples from 6 patients with Chlamydia-associated arthritis. The study findings were compared with 24-hour cultures of HeLa cells infected with Chlamydia trachomatis EB, Results, Persistent C trachomatis infection was found in all 6 synovial membrane samples from patients who had either early or chronic arthritis, The infection persisted despite antibiotic treatment, including a 1-month course of doxycycline therapy. Most persistent organisms were atypical reticulate bodies (RBs) found in both fibroblasts and macrophages. Specific, but weak, immunogold staining for all 3 antibodies was found on both intracellular RBs and extracellular EBs, In the SF samples, Chlamydia surface antigens were detected only in phagosomes containing degraded electron-dense materials. Conclusions. The synovial membrane biopsies conducted in this study of Chlamydia-associated ReA/RS revealed atypical RBs with diminished MOMP and LPS expression. Such altered organisms may escape immune surveillance and contribute to disease chronicity; moreover, these organisms may be difficult to detect and treat in some ReA/RS patients. C1 VET AFFAIRS MED CTR,CTR RHEUMATOL IMMUNOL,PHILADELPHIA,PA 19104. KHON KAEN UNIV,KHON KAEN,THAILAND. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. MED COLL PENN,PHILADELPHIA,PA 19129. FU NEI NIH HHS [EY-03324]; NIAMS NIH HHS [AR-42541] NR 45 TC 103 Z9 106 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1995 VL 38 IS 10 BP 1410 EP 1417 DI 10.1002/art.1780381008 PG 8 WC Rheumatology SC Rheumatology GA TA574 UT WOS:A1995TA57400007 PM 7575691 ER PT J AU MURRAY, MJ MURRAY, AB MURRAY, NJ MURRAY, MB AF MURRAY, MJ MURRAY, AB MURRAY, NJ MURRAY, MB TI INFECTIONS DURING SEVERE PRIMARY UNDERNUTRITION AND SUBSEQUENT REFEEDING - PARADOXICAL FINDINGS SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF MEDICINE LA English DT Article DE FAMINE; SUPPRESSED INFECTION; REFEEDING INFECTION AB Background: Our earlier uncontrolled observations during primary famine and subsequent refeeding did not suggest that severe undernutrition inevitably increases vulnerability to infection. Some infections appeared suppressed by famine but reactivated by refeeding. Aims: To examine prospectively the occurrence of infections in a large cohort of primary famine victims before and during refeeding. Methods: From 1973 to 1993, 4382 famine victims aged 14 or more with an estimated weight loss greater than 25% were weighed and examined for infection before and after one, two, three and four weeks of refeeding. In 137, serum C-reactive protein was measured in an effort to detect latent asymptomatic infections before and after two weeks of refeeding. Refeeding diets included wheat, sorghum, millet, ghee and milk powder. Results: Mean weight loss +/- SD was 28.7 +/- 2.3%. Before refeeding overt infections were found in 4.9%, an incidence rising to 29.1% at two weeks of refeeding and declining after four. Those developing infections gained more weight at two weeks, 4.63 +/- 0.81 kg, than those never infected, 3.94 +/- 0.76 (p = < 0.001 t test). C-reactive protein levels confirmed the presence of latent infections before refeeding. Conclusions: Severe undernutrition can suppress certain infections, mostly those due to intracellular pathogens and especially P, falciparum. Refeeding reactivates suppressed infection and can increase vulnerability to certain new infections especially of viral origin. Those gaining weight the most rapidly may be at greatest risk. Refeeding with foods alien to local culture could play a role in reactivating latent infections. Our findings may be limited to severe undernutrition and not apply to lesser forms or secondary undernutrition in hospital patients. These studies were done during charitable provision of medical care to famine victims. C1 UNIV MINNESOTA,MINNEAPOLIS,MN 55455. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 17 TC 8 Z9 9 U1 0 U2 0 PU ADIS PRESS AUSTRALASIA P/L PI BALGOWLAH PA P.O. BOX 132, BALGOWLAH NSW 2093, AUSTRALIA SN 0004-8291 J9 AUST NZ J MED JI Aust. New Zeal. J. Med. PD OCT PY 1995 VL 25 IS 5 BP 507 EP 511 DI 10.1111/j.1445-5994.1995.tb01496.x PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA TE377 UT WOS:A1995TE37700011 PM 8588773 ER PT J AU SACHS, GS RENSHAW, PF LAFER, B STOLL, AL GUIMARAES, AR ROSENBAUM, JF GONZALEZ, RG AF SACHS, GS RENSHAW, PF LAFER, B STOLL, AL GUIMARAES, AR ROSENBAUM, JF GONZALEZ, RG TI VARIABILITY OF BRAIN LITHIUM LEVELS DURING MAINTENANCE TREATMENT - A MAGNETIC-RESONANCE SPECTROSCOPY STUDY SO BIOLOGICAL PSYCHIATRY LA English DT Article DE BRAIN; LITHIUM; MAGNETIC RESONANCE SPECTROSCOPY; BIPOLAR DISORDER; BRAIN IMAGING ID BIPOLAR DISORDER; NMR-SPECTROSCOPY; IN-VIVO; LI-7; PHARMACOKINETICS; ERYTHROCYTE; PREDICTION; HUMANS; MANIA AB In vivo magnetic resonance spectroscopy (MRS) was used to determine the relationship between serum and brain lithium levels in bipolar patients (n = 25). Over the broad range of serum lithium levels observed, the correlation (r =.68) with brain lithium levels was high, This correlation was much weaker (r =.39) when limited to only those patients with serum lithium levels in the range of 0.6-1.0 mmol/l. This variability may account for failure of lithium prophylaxis in some patients who have serum lithium levels in the therapeutic range. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,HARVARD BIPOLAR RES PROGRAM,BOSTON,MA. MCLEAN HOSP,CTR BRAIN IMAGING,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR NMR,MGH,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,PSYCHOPHARMACOL UNIT,BOSTON,MA 02115. MIT,DEPT NUCL ENGN,RADIOL SCI PROGRAM,CAMBRIDGE,MA 02139. RP SACHS, GS (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,WACC 815,BOSTON,MA 02114, USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 22 TC 41 Z9 41 U1 2 U2 2 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD OCT 1 PY 1995 VL 38 IS 7 BP 422 EP 428 DI 10.1016/0006-3223(94)00324-V PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RY993 UT WOS:A1995RY99300002 PM 8672602 ER PT J AU VENUGOPALAN, V NISHIOKA, NS MIKIC, BB AF VENUGOPALAN, V NISHIOKA, NS MIKIC, BB TI THE THERMODYNAMIC RESPONSE OF SOFT BIOLOGICAL TISSUES TO PULSED ULTRAVIOLET-LASER IRRADIATION SO BIOPHYSICAL JOURNAL LA English DT Article ID PHOTOACOUSTIC INJURY; THERMAL-DAMAGE; ABLATION; COLLAGEN; CORNEA; PRESSURE; DURATION; WATER; WAVES; SKIN AB The physical mechanisms that enable short pulses of high-intensity ultraviolet laser radiation to remove tissue, in a process known as laser ablation, remain obscure. The thermodynamic response of biological tissue to pulsed laser irradiation was investigated by measuring and subsequently analyzing the stress transients generated by pulsed argon fluorine (ArF, lambda = 193 nm) and krypton fluorine (KrF, lambda = 248 nm) excimer laser irradiation of porcine dermis using thin-film piezoelectric transducers. For radiant exposures that do not cause material removal, the stress transients are consistent with rapid thermal expansion of the tissue. At the threshold radiant exposure for ablation, the peak stress amplitude generated by 248 nm irradiation is more than an order of magnitude larger than that produced by 193 nm irradiation. For radiant exposures where material removal is achieved, the temporal structure of the stress transient indicates that the onset of material removal occurs during irradiation. In this regime, the variation of the peak compressive stress with radiant exposure is consistent with laser-induced rapid surface vaporization. For 193 nm irradiation, ionization of the ablated material occurs at even greater radiant exposures and is accompanied by a change in the variation of peak stress with radiant exposure consistent with a plasma-mediated ablation process. These results suggest that absorption of ultraviolet laser radiation by the extracellular matrix of tissue leads to decomposition of tissue on the time scale of the laser pulse. The difference in volumetric energy density at ablation threshold between the two wavelengths indicates that the larger stresses generated by 248 nm irradiation may facilitate the onset of material removal. However, once material removal is achieved, the stress measurements demonstrate that energy not directly responsible for target decomposition contributes to increasing the specific energy of the plume (and plasma, when present), which drives the gas dynamic expansion of ablated material. This provides direct evidence that ultraviolet laser ablation of soft biological tissues is a surface-mediated process and not explosive in nature. C1 MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. RP VENUGOPALAN, V (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,M-S BHX 630,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 49 TC 28 Z9 28 U1 1 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1995 VL 69 IS 4 BP 1259 EP 1271 PG 13 WC Biophysics SC Biophysics GA TJ021 UT WOS:A1995TJ02100005 PM 8534796 ER PT J AU MUNN, LL KOENIG, GC JAIN, RK MELDER, RJ AF MUNN, LL KOENIG, GC JAIN, RK MELDER, RJ TI KINETICS OF ADHESION MOLECULE EXPRESSION AND SPATIAL-ORGANIZATION USING TARGETED SAMPLING FLUOROMETRY SO BIOTECHNIQUES LA English DT Article ID HUMAN ENDOTHELIAL-CELLS; P-SELECTIN; FLOW; LYMPHOCYTES; MODULATION; INTEGRINS; RECEPTORS AB Cellular interactions with the vascular wall under flow conditions are controlled, in part, by the density of adhesion molecules on endothelial cells. The spatial arrangement and absolute levels of these molecules over the endothelium are therefore important determinants of cellular localization. Many biochemical and functional studies have characterized the interactions between leukocytes and endothelial monolayers, but no reliable method has been reported for quantifying the spatial expression of adhesion molecules opt intact endothelial cell monolayers. We report the development of targeted sampling fluorometry (TSF), which uses standard immuno-staining, fluorescence microscopy and digital image analysis techniques to analyze cell surface molecule expression on a cell-by-cell basis. This technique is performed on an intact monolayer and results in cellular intensity distributions that reflect spatial heterogeneity in adhesion molecule expression. We demonstrate the use of targeted sampling fluorometry in a study of the kinetics of tumor necrosis factor alpha-induced activation of human umbilical vein endothelial cell monolayers and show that the spatial patterns of adhesion molecule expression correlate with the locations of bound lymphocytes. C1 MASSACHUSETTS GEN HOSP, DEPT RADIAT ONCOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 22 TC 17 Z9 17 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1995 VL 19 IS 4 BP 622 EP + PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY991 UT WOS:A1995RY99100022 PM 8777057 ER PT J AU KOBAYASHI, M LAVER, JH KATO, T MIYAZAKI, H OGAWA, M AF KOBAYASHI, M LAVER, JH KATO, T MIYAZAKI, H OGAWA, M TI RECOMBINANT HUMAN THROMBOPOIETIN (MPL LIGAND) ENHANCES PROLIFERATION OF ERYTHROID PROGENITORS SO BLOOD LA English DT Note ID COLONY-STIMULATING FACTOR; SERUM-FREE CULTURE; BURST-PROMOTING ACTIVITY; HUMAN GM-CSF; HEMATOPOIETIC PROGENITORS; HUMAN-ERYTHROPOIETIN; GROWTH; CELLS; DIFFERENTIATION; INTERLEUKIN-3 AB We have studied the effects of recombinant human thrombopoietin (TPO, Mpl ligand) on human hematopoiesis in vitro. TPO alone did not support erythroid burst formation but, in the presence of erythropoietin, it enhanced erythroid burst formation from CD34(+) bone marrow and cord blood cells. The burst-promoting activity (BPA) was stronger under 5% serum than 30% serum conditions. The direct nature of BPA effects was documented by replating studies of early erythroid bursts. The BPA of TPO was less than that of interleukin-3 but was comparable with that of granulocyte/macrophage colony-stimulating factor and steel factor. The soluble form of Mpl receptor inhibited burst enhancing effects of TPO, suggesting that the BPA affects of TPO are mediated through the Mpl receptor. These results further delineate the physiologic roles of TPO and may aid in the determination of the clinical usages of TPO. (C) 1995 by The American Society of Hematology. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT PEDIAT & MED,CHARLESTON,SC 29425. KIRIN BREWERY CO LTD,PHARMACEUT RES LAB,MAEBASHI,GUMMA,JAPAN. FU NIDDK NIH HHS [DK32294] NR 39 TC 146 Z9 147 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1995 VL 86 IS 7 BP 2494 EP 2499 PG 6 WC Hematology SC Hematology GA RW497 UT WOS:A1995RW49700005 PM 7545458 ER PT J AU KRAMM, CM SENAESTEVES, M BARNETT, FH RAINOV, NG SCHUBACK, DE YU, JS PECHAN, PA PAULUS, W CHIOCCA, EA BREAKEFIELD, XO AF KRAMM, CM SENAESTEVES, M BARNETT, FH RAINOV, NG SCHUBACK, DE YU, JS PECHAN, PA PAULUS, W CHIOCCA, EA BREAKEFIELD, XO TI GENE-THERAPY FOR BRAIN-TUMORS SO BRAIN PATHOLOGY LA English DT Review ID HERPES-SIMPLEX VIRUS; ENDOTHELIAL GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; WILD-TYPE P53; ADENOVIRUS EARLY REGION-4; THYMIDINE KINASE GENE; ANTI-SENSE RNA; JUNCTIONAL PROTEIN CONNEXIN-43; PACKAGING CELL-LINE; PLATELET FACTOR-IV AB Gene therapy has opened new doors for treatment of neoplastic diseases. This new approach seems very attractive, especially for glioblastomas, since treatment of these brain tumors has failed using conventional therapy regimens. Many different modes of gene therapy for brain tumors have been tested in culture and in vivo. Many of these approaches are based on previously established anti-neoplastic principles, like prodrug activating enzymes, inhibition of tumor neovascularization, and enhancement of the normally weak anti-tumor immune response. Delivery of genes to tumor cells has been mediated by a number of viral and synthetic vectors. The most widely used paradigm is based on the activation of ganciclovir to a cytotoxic compound by a viral enzyme, thymidine kinase, which is expressed by tumor cells, after the gene has been introduced by a retroviral vector. This paradigm has proven to be a potent therapy with minimal side effects in several rodent brain tumor models, and has proceeded to phase 1 clinical trials. In this review, current gene therapy strategies and vector systems for treatment of brain tumors will be described and discussed in light of further developments needed to make this new treatment modality clinically efficacious. C1 MASSACHUSETTS GEN HOSP,CTR NEUROSCI,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. UNIV DUSSELDORF,CHILDRENS HOSP,W-4000 DUSSELDORF,GERMANY. BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,NEUROL SERV,BOSTON,MA 02115. UNIV HALLE WITTENBERG,DEPT NEUROSURG,HALLE,GERMANY. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. UNIV ZURICH HOSP,DEPT PATHOL,INST NEUROPATHOL,CH-8091 ZURICH,SWITZERLAND. NR 347 TC 79 Z9 79 U1 1 U2 1 PU INT SOC NEUROPATHOLOGY PI ZURICH PA ISN JOURNAL PO BOX, CH-8033 ZURICH, SWITZERLAND SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD OCT PY 1995 VL 5 IS 4 BP 345 EP 381 DI 10.1111/j.1750-3639.1995.tb00615.x PG 37 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA TK374 UT WOS:A1995TK37400003 PM 8974620 ER PT J AU TELLES, C KARNO, M MINTZ, J PAZ, G ARIAS, M TUCKER, D LOPEZ, S AF TELLES, C KARNO, M MINTZ, J PAZ, G ARIAS, M TUCKER, D LOPEZ, S TI IMMIGRANT FAMILIES COPING WITH SCHIZOPHRENIA - BEHAVIORAL FAMILY INTERVENTION V CASE-MANAGEMENT WITH A LOW-INCOME SPANISH-SPEAKING POPULATION SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID EXPRESSED EMOTION; CONTROLLED TRIAL; RELAPSE AB Background. This investigation compared the effectiveness and cross-cultural applicability of behavioural family management (BFM) and standard case management in preventing exacerbation of symptoms and relapse in schizophrenia. Method. Forty low-income Spanish-speaking people with a diagnosis of schizophrenia were randomly assigned to receive standard case management or behavioural family management after stabilisation with neuroleptic medication. Results. Survival analyses indicated that among the less acculturated patients BFM was significantly related to greater risk of exacerbation of symptoms. Among the more acculturated patients, risk of exacerbation could be predicted by medication compliance but not by type of intervention. In analyses of symptom severity and functional status at 1-year follow-up, the level of patient acculturation was found to be significantly related to various measures of treatment outcome. Conclusion. Sociocultural factors affect responses to different types of intervention. The results did not support earlier findings of a beneficial effect of BFM when applied to a socioculturally diverse population. C1 W LOS ANGELES VET ASSOC MED CTR,LOS ANGELES,CA. SANTA MONICA W MENTAL HLTH SERV,SANTA MONICA,CA. RP TELLES, C (reprint author), UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,300 UCLA MED PLAZA,SUITE 2236,LOS ANGELES,CA 90024, USA. RI Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 FU NIMH NIH HHS [MH 30911] NR 22 TC 89 Z9 89 U1 1 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD OCT PY 1995 VL 167 BP 473 EP 479 DI 10.1192/bjp.167.4.473 PG 7 WC Psychiatry SC Psychiatry GA TA964 UT WOS:A1995TA96400010 PM 8829715 ER PT J AU SCHNEIDER, E AF SCHNEIDER, E TI CONSUMER HEALTH USA - ESSENTIAL INFORMATION FROM THE FEDERAL HEALTH NETWORK - REES,AM SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Book Review RP SCHNEIDER, E (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1995 VL 83 IS 4 BP 521 EP 522 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA TB589 UT WOS:A1995TB58900026 ER PT J AU SCHNEIDER, E AF SCHNEIDER, E TI THE CONSUMER HEALTH INFORMATION SOURCE-BOOK, 4TH EDITION - REES,AM SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Book Review RP SCHNEIDER, E (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 1995 VL 83 IS 4 BP 521 EP 522 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA TB589 UT WOS:A1995TB58900025 ER PT J AU MUNTZ, HG JONES, MA GOFF, BA FULLER, AF NIKRUI, N RICE, LW TARRAZA, HM AF MUNTZ, HG JONES, MA GOFF, BA FULLER, AF NIKRUI, N RICE, LW TARRAZA, HM TI MALIGNANT MIXED MULLERIAN TUMORS OF THE OVARY - EXPERIENCE WITH SURGICAL CYTOREDUCTION AND COMBINATION CHEMOTHERAPY SO CANCER LA English DT Article DE OVARIAN NEOPLASM; MALIGNANT MIXED MULLERIAN TUMOR; MALIGNANT MIXED MESODERMAL TUMOR; CARCINOSARCOMA; CHEMOTHERAPY; CISPLATIN; DOXORUBICIN; COMBINED MODALITY THERAPY ID GYNECOLOGIC-ONCOLOGY-GROUP; COLONY-STIMULATING FACTOR; FEMALE GENITAL-TRACT; MESODERMAL TUMORS; DRUG-THERAPY; SARCOMA; CARCINOSARCOMAS; DOXORUBICIN; DACARBAZINE; ADRIAMYCIN AB Background. The role of surgical cytoreduction and combination chemotherapy for malignant mixed mullerian tumors (MMMT) of the ovary was evaluated. Methods. A retrospective review of 27 women with ovarian MMMT treated from 1980 to 1990 was performed. Results. The International Federation of Gynecology and Obstetrics stages for the 27 women were 1 Stage I, 3 Stage II, 17 Stage III, and 6 Stage IV. Only 10 of the 23 patients with Stage III or,IV disease were cytoreduced optimally. With respect to postoperative therapy, 3 women received no treatment, 6 were treated with whole abdomen radiotherapy, 1 received melphalan, and 17 received chemotherapy incorporating a platinum agent (3), doxorubicin (4), or both (10). The significant prognostic factors were stage (P < 0.001) and, for women with Stage III or IV disease, the feasibility of cytoreductive surgery (P = 0.03). The four patients in Stages I or II remained disease free after an interval of at least 5 years. The median and 5-year survival rates for patients with Stages III or IV disease was 18 months and 8%, respectively. Patients in Stage III or IV for whom optimal cytoreduction was not possible had a 2-year survival of 14%, whereas optimal cytoreduction was associated with a 52% 2-year survival. Median survival for the 14 women with Stage III or IV ovarian MMMT treated with combination chemotherapy was 25 months and nine women achieved progression free intervals of greater than 18 months. Conclusions. Aggressive surgical cytoreduction followed by combination chemotherapy may result in improved progression free intervals for women with advanced ovarian MMMT. However, a major improvement in prognosis for this rare malignancy has not yet been achieved. C1 MASSACHUSETTS GEN HOSP,VINCENT MEM GYNECOL SERV,BOSTON,MA 02114. MAINE MED CTR,DEPT PATHOL,PORTLAND,ME 04102. MAINE MED CTR,DEPT OBSTET & GYNECOL,PORTLAND,ME 04102. NR 39 TC 49 Z9 50 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 1995 VL 76 IS 7 BP 1209 EP 1213 DI 10.1002/1097-0142(19951001)76:7<1209::AID-CNCR2820760717>3.0.CO;2-V PG 5 WC Oncology SC Oncology GA RV692 UT WOS:A1995RV69200016 PM 8630899 ER PT J AU CAO, J HONG, CH ROSEN, L VESCIO, RA SMULSON, M LICHTENSTEIN, AK BERENSON, JR AF CAO, J HONG, CH ROSEN, L VESCIO, RA SMULSON, M LICHTENSTEIN, AK BERENSON, JR TI DELETION OF GENETIC MATERIAL FROM A POLY(ADP-RIBOSE) POLYMERASE-LIKE GENE ON CHROMOSOME-13 OCCURS FREQUENTLY IN PATIENTS WITH MONOCLONAL GAMMOPATHIES SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MULTIPLE-MYELOMA; ADP-RIBOSYLATION; UNITED-STATES; DNA; CANCER; CELLS; CARCINOGENESIS; EXPRESSION; DEPLETION; LEUKEMIA AB Recently, by using a probe far the nuclear DNA repair enzyme poly(ADP-ribose) polymerase gene, a pseudogene was found on the long arm of chromosome 13, RFLP analysis demonstrates the presence of a common ''A'' allele and a rare (''B'' allele, which has a deletion of approximately 200 bp, This deletion occurs more frequently in blacks than in whites in the United States, In two B-cell malignancies, Burkitt's and follicular lymphomas, there is a marked increased frequency of the expression of the B allele. Thus, we have analyzed the frequency of this allele in another B-cell malignancy, multiple myeloma (MM), which is also more frequently observed in blacks, We studied 97 patients with MM (41 black and 56 white patients) and 30 patients with the related disorder monoclonal gammopathy of undetermined significance (MGUS; 13 black and 17 white patients), The results demonstrate that the overall frequency of B allele expression (37%) is higher than in a noncancer control population (23%; P < 0.01), This difference is mainly due to the much higher frequency of B expression in black patients (62 versus 35% in black controls; P < 0.01), whereas there is no significant difference in white patients (18 versus 14% in white controls), Overall, B allelic frequency is similar in patients with MM and MGUS. Matched germline and tumor DNA show identical patterns of expression of these alleles, These results suggest germline B allelic expression predisposes one to MM and MGUS. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DIV HEMATOL ONCOL,LOS ANGELES,CA 90073. JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. GEORGETOWN UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007. NR 30 TC 14 Z9 15 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT-NOV PY 1995 VL 4 IS 7 BP 759 EP 763 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RZ110 UT WOS:A1995RZ11000010 PM 8672993 ER PT J AU Rustgi, AK Xu, L Pinney, D Sterner, C Beauchamp, R Schmidt, S Gusella, JF Ramesh, V AF Rustgi, AK Xu, L Pinney, D Sterner, C Beauchamp, R Schmidt, S Gusella, JF Ramesh, V TI Neurofibromatosis 2 gene in human colorectal cancer SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID TUMORIGENESIS AB Colon cancers commonly have allelic losses of chromosome 22q, which suggests the presence of a tumor suppressor gene on 22q. The candidate tumor suppressor gene on 22q is the neurofibromatosis 2(NF2) gene. Using single strand conformation polymorphism (SSCP) analysis, we screened 24 pairs of colorectal cancer and adjacent normal mucosa, as well as 10 colon cancer cell lines from non-NF2 patients, for mutations in the coding sequence of the NF2 gene. Two SSCP variants, one in exon 14 and another one in exon 16, were detected in two of the sporadic colorectal cancers, but not in adjacent normal mucosa samples. Sequencing of these variants in one tumor detected an A-to-G transition in bp 1459 of the NF2 cDNA, resulting in the change of Ile to Val at codon 487 of merlin, the NF2 protein product. The other tumor showed a 2-bp (CT) deletion in the intronic sequence of the alternatively spliced exon 16. These results suggest that the NF2 gene is probably involved in some colorectal tumors, but is not the critical chromosome 22q tumor suppressor gene involved in colon tumorigenesis. C1 MASSACHUSETTS GEN HOSP EAST,MOLEC NEUROGENET LAB,CHARLESTON,MA 02129. MASSACHUSETTS GEN HOSP EAST,GASTROINTESTINAL UNIT,CHARLESTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. RI Schmidt, Stephen/B-5398-2012 FU NIDDK NIH HHS [NIDDK 43351]; NINDS NIH HHS [NS24279] NR 15 TC 25 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 1 PY 1995 VL 84 IS 1 BP 24 EP 26 DI 10.1016/0165-4608(95)00059-3 PG 3 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA TK798 UT WOS:A1995TK79800005 PM 7497438 ER PT J AU MANOME, Y WEN, PY HERSHOWITZ, A TANAKA, T ROLLINS, BJ KUFE, DW FINE, HA AF MANOME, Y WEN, PY HERSHOWITZ, A TANAKA, T ROLLINS, BJ KUFE, DW FINE, HA TI MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) GENE TRANSDUCTION - AN EFFECTIVE TUMOR VACCINE STRATEGY FOR NON-INTRACRANIAL TUMORS SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE TUMOR VACCINE; MCP-1; MALIGNANT GLIOMA; 9L GLIOSARCOMA MODEL ID GROWTH-FACTOR; REDUCED TUMORIGENICITY; INTERFERON-GAMMA; BEARING MICE; CELLS; EXPRESSION; GLIOMA; INTERLEUKIN-2; GLIOBLASTOMA; IMMUNITY AB Recently, there has been renewed interest in the concept of tumor vaccines using genetically engineered tumor cells expressing a variety of cytokines to increase their immunogenicity. Human MCP-1 (JE) is a potent chemoattractant and activator of monocytes and T lymphocytes and thus a good candidate gene for a tumor vaccine. We therefore evaluated the efficacy of vaccines consisting of irradiated tumor cells transduced with the murine MCP-1 gene in the syngeneic 9L gliosarcoma brain tumor model. 9L cell lines stably expressing murine MCP-1 (9L-JE) and control cell lines expressing neomycin 3' phosphotransferase (9L-Neo) were generated by infection with a Moloney murine leukemia retroviral vector. Fisher 344 rats were immunized with intradermal injections of 5 x 10(5) or 2 x 10(6) irradiated (5000 cGy) 9L-JE, 9L-Neo, and wild-type 9L (9L-WT) cells. Two weeks later immunized and non-immunized animals were challenged with varyious doses of intradermal (5 x 10(6)-5 x 10(7)) or intracerebral (2 x 10(4)-5 x 10(5)) 9L-WT cells. Intradermal tumors grew in all non-immunized animals. No tumors grew in animals immunized with irradiated 9L-JE or 9L-Neo cells and challenged with inocula of fewer than 5 x 10(5) 9L-WT cells. With higher inocula up to 10(7) cells, tumors appeared in all the animals, but subsequently regressed in the immunized animals. Tumors in animals immunized with 9L-JE were always smaller than tumors in the other groups. In addition, only the 9L-JE vaccine protected against tumor inocula of 5 x 10(7) cells. Thus vaccination with MCP-1-expressing cells was able to protect animals against at least a 100-fold larger number of challenge tumor cells than vaccination with control cells. In contrast to studies with intradermal tumors, immunization with 9L-JE and 9L-Neo produced only minimal protection against intracerebral tumors. There was no significant difference between the 9L-JE and 9L-Neo vaccines in intracerebral challenge. This study suggests that tumor vaccines expressing cytokine genes such as MCP-1 can increase the antitumor response. However, the protective effect of these vaccines appears to be largely limited to intradermal tumors rather than intracerebral tumors. C1 DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV NEUROL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. NR 46 TC 49 Z9 49 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD OCT PY 1995 VL 41 IS 4 BP 227 EP 235 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA TH191 UT WOS:A1995TH19100004 PM 7489565 ER PT J AU LI, JJ LI, SA OBERLEY, TD PARSONS, JA AF LI, JJ LI, SA OBERLEY, TD PARSONS, JA TI CARCINOGENIC ACTIVITIES OF VARIOUS STEROIDAL AND NONSTEROIDAL ESTROGENS IN THE HAMSTER-KIDNEY - RELATION TO HORMONAL ACTIVITY AND CELL-PROLIFERATION SO CANCER RESEARCH LA English DT Article ID SYRIAN-HAMSTER; ANTI-ESTROGENS; GOLDEN-HAMSTER; TUBULAR CELLS; METABOLISM; RECEPTOR; ADENOCARCINOMA; TUMORIGENESIS; INDUCTION; TISSUES AB The therapeutic use of estrogens has been associated with an increased risk of same of the most predominant, as well as less prevalent, cancers in women, The estrogen-induced renal tumor is one of the primary animal models to evaluate the carcinogenic properties of estrogens. Correlations were made with various estrogens by using parameters of estrogenicity end points such as competitive binding, progesterone receptor induction, and alterations in prolactin levels; in vitro renal proximal cell proliferation; and in vivo estrogen-induced carcinogenicity. The most potent estrogens were Moxestrol (MOX), diethylstilbestrol (DES), and 17 beta-estradiol, followed by indenestrol B, 16 alpha-hydroxyestrone, and 11 beta-methoxyestradiol with moderate estrogenic activities, whereas 11 beta-methytestradiol, 17 alpha-estradiol, indanestrol, and deoxoestrone were all relatively weaker. As expected, hydrolyzed Premarin (unconjugated estrogens) was strongly estrogenic Of the estrogens tested, MOX was the most potent carcinogenic estrogen in the hamster kidney. Both 16 alpha-hydroxyestrone and 11 beta-methoxyestradiol induced intermediate tumor incidences with distinctly lower frequencies of renal tumor foci compared to the most potent carcinogenic estrogens. However, hamsters treated for 9.0 months with 11 beta-methylestradiol, 17 alpha-estradiol, deoxoestrone, and indanestrol exhibited no tumors. In contrast, treatment with estrone, equilin plus d-equilenin, and hydrolyzed Premarin for the same time period resulted in 100% renal tumor incidences and numerous tumor foci. Cell proliferation studies of cultured hamster kidney proximal tubule cells were carried out at varying estrogen concentrations (0.01-100 nM). Exposure to MOX resulted in consistently high renal cell proliferative response over a concentration range of 0.1-10 nM. Strongly carcinogenic estrogens such as estrone had a maximal renal cell proliferation response (2.4-fold above untreated control levels) between 0.1 and 10 nM, DES and 17 beta-estradiol responded at 1.0 nM, and 4-hydroxyestradiol responded at 10 nM. Interestingly, exposure to ethinylestradiol, a potent estrogen, at similar or higher doses as those used for DES and 17 beta-estradiol, yielded only a 10% renal tumor incidence and induced only a 1.7-fold increase in proximal tubule cell proliferation. In contrast, 17 alpha-estradiol, deoxoestrone, indanestrol, and 11 beta-methylestradiol, all weakly estrogenic and noncarcinogenic agents, had relatively little effect on tubule cell proliferation. The hydrolyzed Premarin exhibited a maximal 2.0-fold cell proliferative response at 10 nM. The present results provide clear evidence that, in the hamster kidney, the degree of carcinogenicity of a given estrogen correlates with its ability to induce proximal tubule cell proliferation in vitro. Therefore, the ability of estrogen to enhance tubule cell proliferation is a more accurate indicator of its carcinogenicity in this system than either the estrogen-responsive end points used or the amount of catechol metabolites generated in this tissue as reported earlier. C1 UNIV KANSAS, MED CTR, DEPT PHARMACOL TOXICOL & THERAPEUT, KANSAS CITY, KS 66160 USA. UNIV KANSAS, MED CTR, DEPT PREVENT MED, KANSAS CITY, KS 66160 USA. UNIV WISCONSIN, SCH MED, DEPT PATHOL, MADISON, WI 53706 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, PATHOL SERV, MADISON, WI 53706 USA. UNIV MINNESOTA, SCH MED, DEPT ANAT, MINNEAPOLIS, MN 55417 USA. RP LI, JJ (reprint author), UNIV KANSAS, MED CTR, CANC CTR, DIV ETIOL & PREVENT HORMONAL CANC, HORMONAL CARCINOGENESIS LAB, KANSAS CITY, KS 66160 USA. FU NCI NIH HHS [CA22008, CA58030] NR 48 TC 107 Z9 107 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 1995 VL 55 IS 19 BP 4347 EP 4351 PG 5 WC Oncology SC Oncology GA RX114 UT WOS:A1995RX11400028 PM 7671246 ER PT J AU Mody, FV Singh, BN AF Mody, FV Singh, BN TI Silent ischemia in the elderly - Overview SO CARDIOLOGY IN THE ELDERLY LA English DT Editorial Material ID MYOCARDIAL-ISCHEMIA; UNSTABLE ANGINA C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. RP Mody, FV (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CARDIOL SECT,DIV CARDIOL,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU CURRENT SCIENCE PI PHILADELPHIA PA 400 MARKET STREET,SUITE 750 ATTN:SARAH WHEALEN/SUB MGR, PHILADELPHIA, PA 19106 SN 1058-3661 J9 CARDIOL ELDER JI Cardiol. Elder. PD OCT PY 1995 VL 3 IS 5 BP 321 EP 325 PG 5 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA TR206 UT WOS:A1995TR20600001 ER PT J AU Moreu, J Silver, MT Palacios, IF Jang, IK AF Moreu, J Silver, MT Palacios, IF Jang, IK TI Morphologic characteristics of restenotic lesions following coronary interventions: Balloon angioplasty versus directional atherectomy: Can we speculate about the mechanism of restenosis from morphologic analysis? SO CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS LA English DT Article DE percutaneous transluminal coronary angioplasty; quantitative coronary analysis; lesion morphology; restenosis ID ANGIOGRAPHIC MORPHOLOGY; ARTERY AB In order to compare the processes of restenosis after balloon angioplasty as compared to that after directional coronary atherectomy, we performed qualitative and quantitative analysis of 72 lesions in 68 patients with recurrent ischemia following a successful initial procedure. For each lesion, we reviewed the pre-intervention, immediate post-intervention, and restenosis angiograms. The morphology of the restenotic lesions could not be predicted from pre- or post-intervention angiograms. The restenotic lesions after directional atherectomy, as compared to balloon angioplasty, did not show a statistically significant difference, although there was a trend to more eccentric narrowing. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0098-6569 J9 CATHETER CARDIO DIAG JI Catheter. Cardiovasc. Diagn. PD OCT PY 1995 VL 36 IS 2 BP 103 EP 109 DI 10.1002/ccd.1810360202 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UD789 UT WOS:A1995UD78900001 PM 8829829 ER PT J AU LIANG, P AVERBOUKH, L ZHU, WM HALEY, T PARDEE, AB AF LIANG, P AVERBOUKH, L ZHU, WM HALEY, T PARDEE, AB TI MOLECULAR CHARACTERIZATION OF THE MURINE THYMIDYLATE KINASE GENE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID DNA-SYNTHESIS; CELLS; TRANSCRIPTION; YEAST; EXPRESSION; INDUCTION; PROMOTER; PROTEIN; GROWTH AB Thymidylate kinase (TMK) catalyzes an essential reaction of converting dTMP to dTDP, leading to formation of the DNA precursor dTTP. Unlike the preceding enzymes, thymidine kinase and thymdylate synthase, little is known about regulation of TMK after mammalian cells exit from quiescence and enter the cell cycle. In this study, cDNA of murine TMK was isolated and characterized. Murine TMK gene expression in nontransformed BALB/c 3T3 cells was shown to be regulated during G(0) to S-phase transit at both mRNA and enzyme activity levels. Its timing was distinctive from that of thymidine kinase and thymdylate synthase. In contrast, the regulation of TMK in response to serum growth factor stimulation was abolished in cells transformed by either SV40 or Kirsten viruses, and tmk expression became constitutively elevated. This finding is in concordance with previous results showing that transformed cells exhibit more relaxed control than normal cells in their initiation of DNA replication. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA22427] NR 18 TC 9 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD OCT PY 1995 VL 6 IS 10 BP 1333 EP 1338 PG 6 WC Cell Biology SC Cell Biology GA RZ082 UT WOS:A1995RZ08200016 PM 8845311 ER PT J AU PAHLAVANI, MA HARRIS, MD RICHARDSON, A AF PAHLAVANI, MA HARRIS, MD RICHARDSON, A TI THE AGE-RELATED DECLINE IN THE INDUCTION OF IL-2 TRANSCRIPTION IS CORRELATED TO CHANGES IN THE TRANSCRIPTION FACTOR NFAT SO CELLULAR IMMUNOLOGY LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; HUMAN INTERLEUKIN-2 GENE; 5' FLANKING REGION; T-CELL ACTIVATION; CYCLOSPORINE-A; IMMUNE FUNCTION; RECEPTOR EXPRESSION; ANTIGEN RECEPTOR; NUCLEAR FACTOR; PROTEIN AB The effect of aging on the induction of IL-2 transcription by concanavalin A was studied in spleen lymphocytes isolated from young (4-6 months) and old (24 months) male Fischer 344 rats. The induction of IL-2 mRNA levels and IL-2 transcription were 40 to 50% lower for spleen lymphocytes isolated from old rats compared to spleen lymphocytes isolated from young rats. Because the transcription factor NFAT (nuclear factor activating IL-2 transcription) plays a major role in the regulation of IL-2 transcription, the DNA binding activity of NFAT in nuclear extracts of concanavalin A-stimulated lymphocytes was measured using a gel shift assay. The ability of nuclear extracts isolated from either total spleen lymphocytes or T cells to bind the NFAT oligonucleotide decreased 50 to 60% with age. Therefore, the age-related decrease in the expression of IL-2 appears to occur at the level of transcription and involves the transcription factor NFAT. (C) 1995 Academic Press, Inc. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. RP PAHLAVANI, MA (reprint author), UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,HLTH SCI CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [AG00677, AG01548] NR 54 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 1 PY 1995 VL 165 IS 1 BP 84 EP 91 DI 10.1006/cimm.1995.1190 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA RX039 UT WOS:A1995RX03900012 PM 7671328 ER PT J AU DEFOUGEROLLES, A SPRINGER, TA AF DEFOUGEROLLES, A SPRINGER, TA TI IDEAS CRYSTALLIZED ON IMMUNOGLOBULIN SUPERFAMILY-INTEGRIN INTERACTIONS SO CHEMISTRY & BIOLOGY LA English DT Article ID BINDING; ADHESION; CD11B/CD18; ICAM-1; DOMAIN AB Interactions between immunoglobulin superfamily (IgSF) members and integrins are central to lymphocyte homing, leukocyte emigration into tissues at inflammatory sites, and in cell-cell interactions that lead to immune responses. Recent X-ray crystal structures reveal that the interaction of a divalent cation found in the integrin structure with an acidic residue from the IgSF partner may be important in binding. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP DEFOUGEROLLES, A (reprint author), UNIV CAMBRIDGE,SCH CLIN MED,WELLCOME TRUST IMMUNOL UNIT,CAMBRIDGE CB2 2SP,ENGLAND. FU Wellcome Trust NR 21 TC 6 Z9 6 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD OCT PY 1995 VL 2 IS 10 BP 639 EP 643 DI 10.1016/1074-5521(95)90024-1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TC714 UT WOS:A1995TC71400002 PM 9383469 ER PT J AU KACMAREK, RM KIRMSE, M NISHIMURA, M MANG, H KIMBALL, WR AF KACMAREK, RM KIRMSE, M NISHIMURA, M MANG, H KIMBALL, WR TI THE EFFECTS OF APPLIED VS AUTO-PEEP ON LOCAL LUNG UNIT PRESSURE AND VOLUME IN A 4-UNIT LUNG MODEL SO CHEST LA English DT Article DE APPLIED PEEP; ARDS; AUTO-PEEP; COMPLIANCE; END-EXPIRATORY LUNG VOLUME; LUNG MODEL; MECHANICAL VENTILATION; RESISTANCE; TIME CONSTANT ID INVERSE RATIO VENTILATION; ACUTE RESPIRATORY-FAILURE; FREQUENCY JET VENTILATION; END-EXPIRATORY PRESSURE; DISTRESS SYNDROME; CONVENTIONAL VENTILATION; MECHANICAL VENTILATION; INTRINSIC PEEP; OXYGENATION; FLOW AB Background: The application of positive end-expiratory pressure (PEEP) and maintenance of increased mean airway pressure (MAP) has been associated with improved oxygenation in adult respiratory distress syndrome. Recently, attention has been directed toward elevating MAP by establishing auto-PEEP when ventilating with an inverse inspiratory to expiratory ratio in opposition to applied PEEP. We theorized that FRC distribution and local lung unit end-expiratory pressure (EEP) would be different when equal levels of PEEP were established by applying PEEP or by producing auto-PEEP. Methods: Using a four-chamber lung model with each chamber having a different time constant (TC), we applied equal levels of applied PEEP (I:E ratio 1:3) and auto-PEEP (I:E ratio 3:1) and evaluated local lung unit EEP and end expiratory lung volume (EELV). Results: During all trials with applied PEEP, local lung unit EEP was equal to applied PEEP, whereas during auto-PEEP local EEP differed (p<0.01). At a tracheal auto-PEEP level of 12.7 cm H2O, the lung unit with the longest TC (slow lung unit) had an EEP of 15.8 cm H2O, while the shortest TC unit (fast lung unit) had an EEP of 10.1 cm H2O (p<0.01). Similarly, local EELVs were more maldistributed with auto-PEEP than with applied PEEP. At a tracheal PEEP level of 12.7 cm H2O, the EELV increase in the slow lung unit with auto-PEEP was 1,054 mt vs 918 with applied PEEP (p<0.01), whereas the fast lung unit's EELV increase with auto-PEEP was 142 mt compared with 212 mt with applied PEEP (p<0.01). Conclusion: Comparing equal levels of auto-PEEP with applied PEEP, a greater maldistribution of local lung unit EEP and EELV was established with the auto-PEEP. During auto-PEEP, the greatest EEP and EELV occurred in the slow lung unit, and the lowest EEP and EELV developed in the fast lung unit. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP KACMAREK, RM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RESP CARE,ELLISON 401,32 FRUIT ST,BOSTON,MA 02114, USA. NR 24 TC 17 Z9 17 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD OCT PY 1995 VL 108 IS 4 BP 1073 EP 1079 DI 10.1378/chest.108.4.1073 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RZ619 UT WOS:A1995RZ61900040 PM 7555122 ER PT J AU LAMURAGLIA, GM ADILI, F SCHMITZRIXEN, T MICHAUD, NA FLOTTE, TJ AF LAMURAGLIA, GM ADILI, F SCHMITZRIXEN, T MICHAUD, NA FLOTTE, TJ TI PHOTODYNAMIC THERAPY INHIBITS EXPERIMENTAL ALLOGRAFT-REJECTION - A NOVEL-APPROACH FOR THE DEVELOPMENT OF VASCULAR BIOPROSTHESES SO CIRCULATION LA English DT Article DE PHOTODYNAMIC THERAPY; ARTERIES; FREE RADICALS; ALLOGRAFTS; REJECTION ID AORTIC ALLOGRAFTS; ANEURYSMS; ARTERIAL; RATS AB Background Biological vascular allografts have proved unsatisfactory because of thrombosis, occlusion, and aneurysmal degeneration during chronic rejection. Photodynamic therapy (PDT), a technique that leads to the production of cytotoxic free radicals, was investigated as a novel method to prepare arterial allografts. Methods and Results Shortly after impregnation with the photosensitizer drug chloroaluminum sulfonated phthalocyanine, infrarenal aortas of ACI rats were PDT-treated and orthotopically grafted in Lewis rats (PDT). The transplanted grafts were sequentially analyzed at 2, 4, and 8 weeks by morphometry, immunohistochemistry, and scanning electron microscopy. Of 25 untreated allografts, 4 (16%) developed aneurysms compared with 0 of 33 in PDT or untreated isografts (ISO, P<.001). PDT treatment of allografts significantly inhibited intimal hyperplasia (P<.001) and resulted in intimal areas comparable to those in ISO. However, medial thickness in both control allografts and PDT grafts was markedly decreased compared with ISO. External graft diameters of control allografts at 8 weeks were significantly enlarged (P<.02) coma pared with PDT or ISO. At all time points, T lymphocytes were found in a substantially larger number in untreated control grafts than in PDT or ISO. Scanning electron microscopy at 4 weeks confirmed complete repopulation with endothelial cells in PDT, which was not seen in the control allografts. Conclusions Our findings suggest that local PDT treatment of arterial allografts inhibits inflammatory infiltration, aneurysmal dilatation, and development of intimal hyperplasia and may be used to develop vascular bioprostheses for use in humans. C1 MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT DERMATOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, WELLMAN PHOTOMED LABS, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. UNIV COLOGNE, DEPT SURG, W-5000 COLOGNE, GERMANY. RP LAMURAGLIA, GM (reprint author), MASSACHUSETTS GEN HOSP, GEN SURG SERV, DIV VASC SURG, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL-02583] NR 34 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 1 PY 1995 VL 92 IS 7 BP 1919 EP 1926 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RW771 UT WOS:A1995RW77100035 PM 7671376 ER PT J AU Wei, MX Tamiya, T Rhee, RJ Breakefield, XO Chiocca, EA AF Wei, MX Tamiya, T Rhee, RJ Breakefield, XO Chiocca, EA TI Diffusible cytotoxic metabolites contribute to the in vitro bystander effect associated with the cyclophosphamide cytochrome P450 2B1 cancer gene therapy paradigm SO CLINICAL CANCER RESEARCH LA English DT Article ID BRAIN-TUMORS; KINASE GENE; CELLS; GLIOMA; RAT; FRACTION; INVIVO AB Tumor cells become sensitive to the inert prodrug cyclophosphamide (CPA) after transfer of the gene encoding cytochrome P450 2B1. This enzyme activates CPA into 4-hydroxycyclophosphamide, which ultimately degrades into acrolein and phosphoramide mustard, the anticancer and DNA-alkylating metabolite, It is imperative that any prodrug-activating gene therapy strategy against cancer possess the capacity to affect the proliferation of tumor cells even when they do not express the transgene (bystander effect), because current methodologies cannot achieve gene transduction in all tumor cells, Prodrug-activating gene therapy schemes described to date exhibit a bystander effect that is not mediated by conditioned medium in culture and may depend on cell contact. In contrast, we find that CPA-sensitized, P450-expressing C6 glioma cells (C6-P450) transfer cytotoxicity to nonexpressing cells by releasing diffusible metabolites through the medium, A 3-h exposure to the prodrug is necessary and sufficient to achieve killing of the transfected cells, and medium conditioned by these cells can kill untransfected cells with similar potency, This bystander effect occurs in the presence of CPA even when only 10% of cells in culture express the P450 2B1 gene, and it is not reproduced by cells that have been irradiated, In an animal model of intracerebral brain tumors, expression of the P450 2B1 gene within the neoplastic cells enhanced significantly the antitumor effect of CPA, even when it was administered systemically, This study shows that CPA/P450 2B1 gene therapy represents a novel tumor-killing strategy that displays an expanded range of cytotoxic action both spatially and temporally within tumor cells and significantly potentiates the anticancer action of CPA when administered i.v. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROGENET LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02129. FU NINDS NIH HHS [NS24279] NR 30 TC 66 Z9 68 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 1995 VL 1 IS 10 BP 1171 EP 1177 PG 7 WC Oncology SC Oncology GA TL085 UT WOS:A1995TL08500014 PM 9815909 ER PT J AU MARSHALL, MD KALES, SN CHRISTIANI, DC GOLDMAN, RH AF MARSHALL, MD KALES, SN CHRISTIANI, DC GOLDMAN, RH TI ARE REFERENCE INTERVALS FOR CARBOXYHEMOGLOBIN APPROPRIATE - A SURVEY OF BOSTON AREA LABORATORIES SO CLINICAL CHEMISTRY LA English DT Article DE CARBON MONOXIDE; CO-OXIMETERS; TOXICOLOGY ID CORONARY-ARTERY DISEASE; CARBON-MONOXIDE INTOXICATION; EXPOSURE AB CO is a leading cause of poisoning deaths in the US today. Treating physicians use the carboxyhemoglobin (COHb) % saturation to guide the diagnosis and treatment of CO intoxication, We conducted a telephone survey of hospitals and laboratories in the Boston area, focusing on methodology for COHb determination and accompanying COHb reference intervals. Among 130 facilities, 23 (18%) provide COHb analysis. All facilities that perform the COHb test utilize dedicated multiwave-length photometry. Reference intervals for COHb varied widely among facilities. Eight of 21 (38%) facilities give unacceptably high ''normal intervals'' for nonsmokers when compared with values available in the literature. Thirteen of 20 (65%) use reference intervals for smokers that are too low, and 3 of 20 (15%) use values that are too high. These reference values provided by the testing facilities may be misleading to the ordering physicians unfamiliar with background COHb saturations. This may lead to misdiagnoses, false reassurances, and perhaps less aggressive treatment than might be warranted, The results of this study argue for wider adoption of COHb reference intervals supported by the current literature. C1 MT SINAI SCH MED,NEW YORK,NY. HARVARD UNIV,CAMBRIDGE HOSP,SCH PUBL HLTH,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SCH PUBL HLTH,PULM UNIT,BOSTON,MA. MASSACHUSETTS RESP HOSP,BRAINTREE,MA. FU NIEHS NIH HHS [ES00002, ES05947] NR 27 TC 17 Z9 17 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 1995 VL 41 IS 10 BP 1434 EP 1438 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA RZ004 UT WOS:A1995RZ00400006 PM 7586513 ER PT J AU SALVATI, EA LIEBERMAN, JR HUK, OL EVANS, BG AF SALVATI, EA LIEBERMAN, JR HUK, OL EVANS, BG TI COMPLICATIONS OF FEMORAL AND ACETABULAR MODULARITY SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 23rd Open Scientific Meeting of the Hip-Society CY FEB, 1995 CL ORLANDO, FL SP Hip Soc, Assoc Arthrit Hip & Knee Surgeons ID PROSTHESES AB The versatility of modular total hip arthroplasties have rapidly extended their applications. However, these new interfaces can lead to complications that were not observed with monolithic components. These problems have been noted with modular femoral and acetabular components and have been associated with the generation of particulate debris. This article reviews the authors' clinical observations and histologic, biomechanic, and spectophotometric evaluations of modular total hip arthroplasties. New data comparing both synovial fluid metal levels in well-fixed and loose monolithic and modular prosthetic hip implants are presented. In modular total hip components synovial fluid cobalt levels correlated positively with patient weight and length of implantation. The generation of particulate debris in modular total hip components may induce periprosthetic osteolysis. Taper locks for femoral components and locking mechanisms for the polyethylene liner and metallic cup must be designed to avoid the production of particulate debris. C1 UNIV CALIF LOS ANGELES,MED CTR,SCH MED,CTR HLTH SCI,DEPT ORTHOPAED SURG,LOS ANGELES,CA 90095. HOSP SPECIAL SURG,HIP & KNEE SERV,NEW YORK,NY 10021. CORNELL UNIV,NEW YORK HOSP,COLL MED,NEW YORK,NY. W LOS ANGELES VET ADM HOSP,LOS ANGELES,CA. MCGILL UNIV,SIR MORTIMER B DAVIS JEWISH HOSP,DIV ORTHOPAED SURG,MONTREAL,PQ,CANADA. GEORGETOWN UNIV,DEPT ORTHOPAED SURG,WASHINGTON,DC. NR 16 TC 34 Z9 34 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1995 IS 319 BP 85 EP 93 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA TA785 UT WOS:A1995TA78500009 PM 7554653 ER PT J AU JACOBS, JJ URBAN, RM GILBERT, JL SKIPOR, AK BLACK, J JASTY, M GALANTE, JO AF JACOBS, JJ URBAN, RM GILBERT, JL SKIPOR, AK BLACK, J JASTY, M GALANTE, JO TI LOCAL AND DISTANT PRODUCTS FROM MODULARITY SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 23rd Open Scientific Meeting of the Hip-Society CY FEB, 1995 CL ORLANDO, FL SP Hip Soc, Assoc Arthrit Hip & Knee Surgeons ID HIP PROSTHESES; CORROSION; COBALT; CHROMIUM; ALLOYS; COMPONENTS AB In this study, the local acid distant distribution of solid and soluble products of corrosion from the head and neck junction of modular femoral total hip prosthetic components were characterized. Particulate corrosion products from retrieved implants and surrounding tissues were analyzed, Serum transport and urinary excretion of metal was measured in correlation with the degree of corrosion at the head and neck junction. Particles of metal oxides, metal chlorides, and chromium phosphate corrosion products were identified on implants of 10 designs from 6 manufacturers. The most abundant solid corrosion product on the implant and within the periprosthetic tissues (size range, <1-200 micrometers) was an amorphous chromium orthophosphate hydrate-rich material. Serum cobalt and urine chromium concentrations were elevated significantly in patients with implants that had moderate to severe corrosion in comparison with those with no to mild corrosion. Solid corrosion products from modular femoral stems may accelerate articular wear via a 3-body mechanism. Phagocytosable particles of these corrosion products may stimulate macrophage-mediated periprosthetic bone loss. Systemic dissemination of metallic corrosion products raises the issue of systemic toxicity; however, no overt evidence of metal toxicity was observed in this study. C1 NORTHWESTERN UNIV,DEPT BIOL MAT,CHICAGO,IL 60611. IMN BIOMAT,KING OF PRUSSIA,PA. MASSACHUSETTS GEN HOSP,ORTHOPED BIOMECH LAB,BOSTON,MA 02114. RP JACOBS, JJ (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR,RUSH ARTHRIT & ORTHOPED INST,DEPT ORTHOPED SURG,CHICAGO,IL 60612, USA. FU NIAMS NIH HHS [AR 39310] NR 31 TC 131 Z9 132 U1 0 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1995 IS 319 BP 94 EP 105 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA TA785 UT WOS:A1995TA78500010 PM 7554654 ER PT J AU CHANDLER, HP AYRES, DK TAN, RC ANDERSON, LC VARMA, AK AF CHANDLER, HP AYRES, DK TAN, RC ANDERSON, LC VARMA, AK TI REVISION TOTAL HIP-REPLACEMENT USING THE S-ROM FEMORAL COMPONENT SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 23rd Open Scientific Meeting of the Hip-Society CY FEB, 1995 CL ORLANDO, FL SP Hip Soc, Assoc Arthrit Hip & Knee Surgeons ID ARTHROPLASTY AB The proximally porous-coated, modular S-ROM femoral component was used in 52 complex total hip revisions done in 48 patients. These patients had severe bone loss, leg length inequality, and instability. Twenty-two patients required structural femoral allografts; 8 had previous resection arthroplasties for sepsis, The mean number of previous hip operations was 3. The stem was press fit, and the metaphyseal sleeve was selectively cemented to the allograft. The preoperative Harris rating was 44 points; at a mean of 3 years, followup was 82 points. Eighty-four percent of the patients were satisfied with their outcomes. No radiographic or histologic evidence of fretting at the modular sleeve-stem junction or along the stem was seen. Significant thigh pain persisted in 2 patients and was directly related to stem diameters >17 mm. Complications in these complex cases were not infrequent, reflecting the need for allograft augmentation, and included greater trochanter bursitis and nonunion in 20 hips, minor nonpropagating fracture in 13 hips, and 12 dislocations. Mechanical loosening occurred in 5 hips. There were no complications attributable to the S-ROM modular femoral component, and the prosthesis has proven to be versatile and did well in these very difficult cases. RP CHANDLER, HP (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,15 PARKMAN ST,SUITE 531,BOSTON,MA 02114, USA. NR 31 TC 68 Z9 70 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 1995 IS 319 BP 130 EP 140 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA TA785 UT WOS:A1995TA78500013 PM 7554622 ER PT J AU MAYOSMITH, WW LEE, MJ AF MAYOSMITH, WW LEE, MJ TI MR-IMAGING OF THE FEMALE PELVIS SO CLINICAL RADIOLOGY LA English DT Review ID HEMORRHAGIC ADNEXAL LESIONS; PLACENTA-PREVIA-PERCRETA; ENDOMETRIAL CARCINOMA; TRANSVAGINAL SONOGRAPHY; MULLERIAN ANOMALIES; MYOMETRIAL INVASION; JUNCTIONAL ZONE; UTERUS; DIFFERENTIATION; CERVIX AB Magnetic resonance (MR) of the female pelvis is now gaining wider acceptance by referring physicians and radiologists. While the cost of the examination relative to ultrasound (US) precludes its use as a general screening test, technological improvements have increased the application of this modality in the study of gynaecological disease. MR offers the advantage of excellent soft tissue contrast, multiplanar imaging capabilities and lack of radiation. The purpose of this paper is to discuss MR techniques, normal MR anatomy of the female pelvis and application of MR to the study of disease processes in the female pelvis. While MR is the imaging modality of choice for neurological and musculoskeletal imaging, image degradation in the pelvis has resulted in poor quality images in the past. Motion artefacts from bowel, moving blood, and patient motion during long acquisitions all contribute to image degradation. In addition, body coil pelvic imaging is subject to decreased image quality when compared with the transmit-receive coils used in cranial and knee applications. However, technological advances such as pelvic phased array coils and fast spin-echo sequences have markedly improved pelvic MR imaging quality overcoming many of these limitations. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. BEAUMONT HOSP,DEPT RADIOL,DUBLIN 9,IRELAND. RP MAYOSMITH, WW (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,WH220,POB 9657,BOSTON,MA 02114, USA. NR 57 TC 9 Z9 9 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD OCT PY 1995 VL 50 IS 10 BP 667 EP 676 DI 10.1016/S0009-9260(05)83310-0 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RZ105 UT WOS:A1995RZ10500001 PM 7586957 ER PT J AU HOCHACHKA, PW LIGGINS, GC GUYTON, GP SCHNEIDER, RC STANEK, KS HURFORD, WE CREASY, RK ZAPOL, DG ZAPOL, WM AF HOCHACHKA, PW LIGGINS, GC GUYTON, GP SCHNEIDER, RC STANEK, KS HURFORD, WE CREASY, RK ZAPOL, DG ZAPOL, WM TI HORMONAL REGULATORY ADJUSTMENTS DURING VOLUNTARY DIVING IN WEDDELL SEALS SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE DIVING METABOLISM; SEAL CATECHOLAMINES; SEAL EPINEPHRINE; SEAL NOREPINEPHRINE; DIVING PHYSIOLOGY ID NITRIC-OXIDE; ELEPHANT SEALS; METABOLISM; INSULIN; ADRENOCEPTORS; GLUCOSE; HEART AB Subadult male Weddell seals were instrumented with microcomputer-based backpacks and were then monitored during voluntary diving and recovery periods in McMurdo Sound, Antarctica. Depth and duration of diving, swim speed, and dive pattern were routinely monitored, An indwelling venous catheter was used to collect plasma samples at various time periods before and following diving episodes, so that changes in plasma concentrations of hormones and of metabolites could be measured, Adrenergic and nitroxidergic regulatory effects were assessed indirectly by measuring concentration changes in catecholamine and cyclic guanosine monophosphate (cGMP), respectively, The studies found that (i), except for dives of less than several minutes, epinephrine and norepinephrine both increased as a function of diving duration, then rapidly decreased during recovery (with a half time of about 10 min), (ii) that the changes in catecholamine concentrations correlated with splenic contraction and an increase in circulating red blood cell mass (hematocrit), (iii) that the changes in catecholamines, especially [epinephrine], were inversely related to insulin/glucagon ratios, which mediated a postdiving hyperglycemia, and (iv) that in long dives (but not short ones) the changes in catecholamines correlated with increasing reliance on anaerobic metabolism, indicated by increased plasma lactate concentrations, These diving-catecholamine relationships during voluntary diving at sea were similar to those observed during enforced submergence (simulated diving) under controlled laboratory conditions, At the end of diving, even while catecholamine concentrations were still high, many of the above effects were rapidly reversed and the reversal appeared to correlate with accelerated nitric oxide production, indirectly indicated by increased plasma cGMP concentrations, Taken together, the data led to the hypothesis of important adrenergic regulation of the diving response in seals, with rapid reversal at the end of diving and during recovery being regulated by nitroxidergic mechanisms. C1 UNIV BRITISH COLUMBIA,DIV SPORTS MED,VANCOUVER,BC V6T 1Z4,CANADA. NATL WOMENS HOSP,AUCKLAND 3,NEW ZEALAND. UNIV IOWA HOSP & CLIN,ORTHOPED CLIN,IOWA CITY,IA 52242. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. UNIV TEXAS,SCH MED,DEPT OBSTET GYNECOL & REPROD SCI,HOUSTON,TX 77030. RP HOCHACHKA, PW (reprint author), UNIV BRITISH COLUMBIA,DEPT ZOOL,6270 UNIV BLVD,VANCOUVER,BC V6T 1Z4,CANADA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 33 TC 27 Z9 27 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol B-Biochem. Molec. Biol. PD OCT PY 1995 VL 112 IS 2 BP 361 EP 375 DI 10.1016/0305-0491(96)85239-4 PG 15 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA TB714 UT WOS:A1995TB71400024 PM 7584864 ER PT J AU BOLL, W GALLUSSER, A KIRCHHAUSEN, T AF BOLL, W GALLUSSER, A KIRCHHAUSEN, T TI ROLE OF THE REGULATORY DOMAIN OF THE EGF-RECEPTOR CYTOPLASMIC TAIL IN SELECTIVE BINDING OF THE CLATHRIN-ASSOCIATED COMPLEX AP-2 SO CURRENT BIOLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; PROTEIN-TYROSINE KINASE; LIGAND-INDUCED INTERNALIZATION; COATED PIT FORMATION; ASSEMBLY POLYPEPTIDES; SELF-PHOSPHORYLATION; MEDIATED ENDOCYTOSIS; INVITRO BINDING; VESICLES; ACTIVATION AB Background: After stimulation of a cell by the mitogenic epidermal growth factor (EGF), the EGF receptor (EGF-R) is cleared from the cell surface in order to turn off receptor signaling. This internalization is mediated via clathrin-coated pits and coated vesicles, and ultimately the receptors are delivered to the lysosome and destroyed. It is believed that clathrin-associated protein complexes or adaptors (APs) link che entrapment of EGF-R and other nutrient and growth-factor receptors to the formation of the clathrin-coated pit. Two classes of APs are known - AP-2, found at the plasma membrane, and AP-1, found in the trans-Golgi network. Activated EGF-R associates with AP-2s at the plasma membrane, but the mechanism responsible for this association is not known. Here, we investigate, in vivo and in vitro, three aspects of the interaction between APs and EGF-R: firstly, we ask whether EGF-R at the plasma membrane distinguishes between AP-I and AP-2; secondly, we ask which part of the receptor's cytoplasmic tail is responsible for binding; finally, we ask whether autophosphorylation by EGF-R is essential for the interaction. Results: We demonstrate that EGF-R displays a selective association for AP-2 over AP-1 in vivo, and that this preferential interaction can also be detected using surface plasmon resonance in vitro. Using a truncated mutant and a kinase-dead mutant of EGF-R, we show that the regulatory domain of the cytoplasmic tail is essential For the recruitment of AP-2 in vivo and that this domain is required for association between purified AP-2 and EGF-R in vitro. Finally, we demonstrate, in vivo and in vitro, that tyrosine auto-phosphorylation by the receptor is not an essential pre-condition for the recruitment of AP-2. Conclusions: EGF-R binds selectively to AP-2s, and the regulatory domain of its cytoplasmic tail is required for this interaction. The lack of correlation between receptor autophosphorylation and AP-2 recruitment suggests that activation of the EGF-R kinase stimulates endocytosis by the phosphorylation of a factor distinct From EGF-R itself as also proposed by others based on experiments measuring receptor traffic and entrapment. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 42 TC 61 Z9 61 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 1 PY 1995 VL 5 IS 10 BP 1168 EP 1178 DI 10.1016/S0960-9822(95)00233-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TA464 UT WOS:A1995TA46400019 PM 8548289 ER PT J AU POWER, WJ KAUFMAN, AH MERAYOLLOVES, J ARRUNATEGUICORREA, V FOSTER, CS AF POWER, WJ KAUFMAN, AH MERAYOLLOVES, J ARRUNATEGUICORREA, V FOSTER, CS TI EXPRESSION OF COLLAGEN-I, COLLAGEN-III, COLLAGEN-IV AND COLLAGEN-V MESSENGER-RNA IN EXCIMER WOUNDED RAT CORNEA - ANALYSIS BY SEMIQUANTITATIVE PCR SO CURRENT EYE RESEARCH LA English DT Article DE CORNEA; EXCIMER LASER; HAZE; POLYMERASE CHAIN REACTION (PCR); WOUND HEALING; COLLAGENS; RAT ID POLYMERASE CHAIN-REACTION; CENTRAL PHOTOREFRACTIVE KERATECTOMY; FOLLOW-UP; RABBIT CORNEA; BOVINE CORNEA; MESSENGER-RNA; LASER; HETEROGENEITY; MYOPIA; METABOLISM AB A semi-quantitative polymerase chain reaction (PCR) methodology was used to evaluate the kinetic changes occurring in collagens I, III, IV and V mRNA in rat cornea following excimer laser keratectomy. cDNA was synthesized from RNA extracted from rat cornea at various times following excimer laser photoablative keratectomy. Collagen cDNA sequences were subsequently amplified using specific sets of oligonucleotide primers. Competitive PCR amplification was carried out using an internal standard so that a semi-quantitative analysis of message for synthesis of collagen types I, III, IV and V could be performed and time course dynamics of message for these collagens studied. There was a biphasic increase in the levels of collagens III, IV and V mRNA following excimer laser keratectomy. Collagen I mRNA levels demonstrated a more sustained increase and were still elevated at 6 weeks following wounding. Collagens IV and V mRNA showed the largest increase with an approximate three fold increase over controls between 4 days and 1 week. Our results demonstrate that upregulation of stromal collagens I, III, and V mRNA and basement membrane collagen IV mRNA occurs in rat cornea following excimer laser keratectomy. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RHODES MOLEC IMMUNOL LAB,IMMUNOL SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA 02114. NR 41 TC 33 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD OCT PY 1995 VL 14 IS 10 BP 879 EP 886 DI 10.3109/02713689508995127 PG 8 WC Ophthalmology SC Ophthalmology GA TB389 UT WOS:A1995TB38900003 PM 8549153 ER PT J AU SEED, B AF SEED, B TI DEVELOPMENTS IN EXPRESSION CLONING SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Article ID EPSTEIN-BARR VIRUS; TUMOR-NECROSIS-FACTOR; PROTEIN-TYROSINE KINASE; MUTANT-CELL LINE; MOLECULAR-CLONING; CDNA CLONING; BIOLOGICAL CHARACTERIZATION; XENOPUS EMBRYOS; ANTIGEN; LIGAND AB Recent years have seen a dramatic expansion in the range of applications of expression cloning techniques. New vectors and detection methods promise to further broaden the applicability of function-based screening approaches to problems in gene discovery. A major theme in the past year has been the introduction of engineered reporter cells that heighten the sensitivity with which clones expressing cDNAs can be identified. RP SEED, B (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 76 TC 30 Z9 31 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD OCT PY 1995 VL 6 IS 5 BP 567 EP 573 DI 10.1016/0958-1669(95)80094-8 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA TA355 UT WOS:A1995TA35500014 PM 7579669 ER PT J AU TONTONOZ, P HU, E SPIEGELMAN, BM AF TONTONOZ, P HU, E SPIEGELMAN, BM TI REGULATION OF ADIPOCYTE GENE-EXPRESSION AND DIFFERENTIATION BY PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR-GAMMA SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID ENHANCER-BINDING-PROTEIN; PHOSPHOENOLPYRUVATE CARBOXYKINASE GTP; 3T3-L1 PREADIPOCYTES; FATTY-ACIDS; TRANSGENIC MICE; CLOFIBRIC ACID; SUPERFAMILY; MEMBER; CELLS; C/EBP AB Peroxisome proliferator activated receptor (PPAR) gamma is an orphan member of the nuclear hormone receptor superfamily and is expressed at high levels specifically in adipose tissue. Recent data suggest that this factor is a central regulator of adipocyte gene expression and differentiation. Fibroblastic cell lines that express PPAR gamma ectopically can be induced to differentiate into fat cells by a variety of lipids and lipid-like activators of PPARs, suggesting that this protein may function to link adipogenesis with systemic lipid metabolism. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NR 51 TC 331 Z9 339 U1 4 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD OCT PY 1995 VL 5 IS 5 BP 571 EP 576 DI 10.1016/0959-437X(95)80025-5 PG 6 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA RY494 UT WOS:A1995RY49400005 PM 8664544 ER PT J AU DRIEVER, W AF DRIEVER, W TI AXIS FORMATION IN ZEBRAFISH SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID FATE MAP; SALMO-GAIRDNERI; CELL MOVEMENTS; ANNUAL FISHES; EARLY EMBRYO; FLOOR PLATE; MUTATION; SPECIFICATION; EXPRESSION; INDUCTION AB Recent advances in our understanding of axis formation and patterning in zebrafish relate the developmental mode of this aspiring genetic model organism to higher vertebrates. The effect of UV irradiation and lithium treatment, as well as detailed early lineage analyses, have shed some light on dorsoventral axis formation. However, the molecular mechanism of axis formation, as well as the identity of a fish Nieuwkoop center, are still open issues. A Vg1 homolog is expressed in zebrafish, and activin as well as the mouse nodal gene product have been demonstrated to induce mesoderm and ectopic axes, respectively, in zebrafish. The zebrafish organizer is defined by the expression domains of goosecoid, axial, and lim1. The cyclops gene is involved in maintaining goosecoid expression in axial mesoderm of the head. Large mutagenesis screens provide the basis for a genetic analysis of axis formation. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP DRIEVER, W (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,13TH ST,BLDG 149,MAIL CODE 1494201,BOSTON,MA 02129, USA. FU NICHD NIH HHS [HD29761] NR 81 TC 45 Z9 45 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD OCT PY 1995 VL 5 IS 5 BP 610 EP 618 DI 10.1016/0959-437X(95)80030-1 PG 9 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA RY494 UT WOS:A1995RY49400010 PM 8664549 ER PT J AU GONZALEZ, E AF GONZALEZ, E TI PUVA FOR PSORIASIS SO DERMATOLOGIC CLINICS LA English DT Review AB The development in 1974 of psoralen photochemotherapy (PUVA) for severe psoriasis transformed the therapeutic setting for this disease from in-patient to ambulatory, presaging the trend in the past decade to reduce hospitalization. The prospective evaluation of this treatment in well-designed, well-controlled studies with the participation of a large cohort of patients, which expanded for 12 years and involved prestigious academic centers in the United States and Europe, is one of the largest medical enterprises ever conducted and is a testament to scientific investigation and collaboration. Besides its contribution to mitigating the suffering of patients with this disease, the intense scientific pursuit by so many investigators has contributed significantly to the understanding of photomedicine, especially photochemical and photobiologic reactions, and to its place in the clinical arena and in the forefront of dermatologic interest. This article is an account of this scientific endeavor, which now enters its third decade, as well as a recognition of its contributors. RP GONZALEZ, E (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,MGH PROFESS OFF BLDG,BOSTON,MA 02114, USA. NR 0 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 1995 VL 13 IS 4 BP 851 EP & PG 0 WC Dermatology SC Dermatology GA TA537 UT WOS:A1995TA53700014 PM 8785889 ER PT J AU MOMTAZ, K FITZPATRICK, TB AF MOMTAZ, K FITZPATRICK, TB TI MODIFICATIONS OF PUVA SO DERMATOLOGIC CLINICS LA English DT Article AB The goal of photochemotherapy in psoriasis is to attempt to lower the number of exposures and the total cumulative doses while still maintaining good control of the disease. PUVA has been modified by using better psoralen preparations and more effective light sources, and it also has been combined With Other treatment modalities. The objectives in modifying PUVA and combining PUVA with other treatment modalities are to increase efficacy, to reduce short- and long-term adverse effects, and to reduce the cost of treatment. Modalities that have been combined with PUVA include topical corticosteroids, anthralin, calcipotriene ointment, methotrexate, WE, retinoids, and cyclosporine. RP MOMTAZ, K (reprint author), MASSACHUSETTS GEN HOSP,CTR DERMATOL LASER,PROFESS OFF BLDG,275 CAMBRIDGE ST,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 1995 VL 13 IS 4 BP 867 EP & PG 0 WC Dermatology SC Dermatology GA TA537 UT WOS:A1995TA53700015 PM 8785890 ER PT J AU STAINIER, DYR WEINSTEIN, BM DETRICH, HW ZON, LI FISHMAN, MC AF STAINIER, DYR WEINSTEIN, BM DETRICH, HW ZON, LI FISHMAN, MC TI CLOCHE, AN EARLY ACTING ZEBRAFISH GENE, IS REQUIRED BY BOTH THE ENDOTHELIAL AND HEMATOPOIETIC LINEAGES SO DEVELOPMENT LA English DT Article DE HEART; ENDOCARDIUM; HEMATOPOIESIS; ZEBRAFISH; CLOCHE ID TRANSCRIPTION FACTOR; VASCULAR ENDOTHELIUM; TYROSINE KINASE; HEART TUBE; CELL FATE; EXPRESSION; VASCULOGENESIS; ANGIOGENESIS; MUTATION; RECEPTOR AB Endothelial and hematopoietic cells appear synchronously on the extra-embryonic membranes of amniotes in structures known as blood islands, This observation has led to the suggestion that these two ventral lineages share a common progenitor, Recently, we have shown in the zebrafish, Danio rerio, that a single cell in the ventral marginal zone of the early blastula can give rise to both endothelial and blood cells as well as to other mesodermal cells (Stainier, D, Y, R,, Lee, R. K, and Fishman, M, C, (1993), Development 119, 31-40; Lee, R, K, K,, Stainier, D, Y, R,, Weinstein, B, M, and Fishman, M, C, (1994), Development 120, 3361-3366), Here we describe a zebrafish mutation, cloche, that affects both the endothelial and hematopoietic lineages at a very early stage. The endocardium, the endothelial lining of the heart, is missing in mutant embryos, This deletion is selective as evidenced by the presence of other endothelial cells, for example those lining the main vessels of the trunk, Early cardiac morphogenesis proceeds normally even in the absence of the endocardium. The myocardial cells form a tube that is demarcated into chambers, beats rhythmically, but exhibits a reduced contractility, This functional deficit is likely due to the absence of the endocardial cells, although it may be a direct effect of the mutation on the myocardial cells, Cell transplantation studies reveal that the endothelial defect, i,e, the endocardial deletion, is a cell-autonomous lesion, consistent with the possibility that cloche is part of a signal transduction pathway, In addition, the number of blood cells is greatly reduced in cloche mutants and the hematopoietic tissues show no expression of GATA-1 or GATA-2, two key hematopoietic transcription factors that are first expressed during early embryogenesis. These results show that cloche is involved in the genesis and early diversification of the endothelial and blood lineages, possibly by affecting a common progenitor cell population. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NORTHEASTERN UNIV,DEPT BIOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 47 TC 350 Z9 357 U1 4 U2 16 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 OCT PY 1995 VL 121 IS 10 BP 3141 EP 3150 PG 10 WC Developmental Biology SC Developmental Biology GA RZ756 UT WOS:A1995RZ75600002 PM 7588049 ER PT J AU ROBERTS, DJ JOHNSON, RL BURKE, AC NELSON, CE MORGAN, BA TABIN, C AF ROBERTS, DJ JOHNSON, RL BURKE, AC NELSON, CE MORGAN, BA TABIN, C TI SONIC HEDGEHOG IS AN ENDODERMAL SIGNAL INDUCING BMP-4 AND HOX GENES DURING INDUCTION AND REGIONALIZATION OF THE CHICK HINDGUT SO DEVELOPMENT LA English DT Article DE GUT; HINDGUT; INDUCTION; HOX; SONIC HEDGEHOG; SHH; BMP-4 ID BETA FAMILY MEMBER; EPITHELIAL DIFFERENTIATION; HOMEOBOX GENES; HOMEOTIC GENE; NEURAL-TUBE; LIMB BUD; EXPRESSION; DROSOPHILA; MESENCHYME; EMBRYOS AB Reciprocal inductive signals between the endoderm and mesoderm are critical to vertebrate gut development, Sonic hedgehog encodes a secreted protein known to act as an inductive signal in several regions of the developing embryo, In this report, we provide evidence to support the role of Sonic hedgehog and its target genes Binp-4 and the Abd-B-related Hox genes in the induction and patterning the chick hindgut. Sonic is expressed in the definitive endoderm at the earliest stage of chick gut formation, Immediately subjacent to Sonic expression in the caudal endoderm is undifferentiated mesoderm, later to become the visceral mesoderm of the hindgut, Genes expressed within this tissue include Bmp-4 (a TGF-beta relative implicated in proper growth of visceral mesoderm) and members of the Abd-B class of Hox genes (known regulators of pattern in many aspects of development), Using virally mediated mis-expression, we show that Sonic hedgehog is sufficient to induce ectopic expression of Bmp-4 and specific Herd genes within the mesoderm. Sonic therefore appears to act as a signal in an epithelial-mesenchymal interaction in the earliest stages of chick hindgut formation. Gut pattern is evidenced later in gut morphogenesis with the presence of anatomic boundaries reflecting phenotypically and physiologically distinct regions, The expression pattern of the Abd-b-like Hox genes remains restricted in the hindgut and these Hox expression domains reflect gut morphologic boundaries. This finding strongly supports a role for these genes in determining the adult gut phenotype, Our results provide the basis for a model to describe molecular controls of early vertebrate hindgut development and patterning, Expression of homologous genes in Drosophila suggest that aspects of gut morphogenesis may be regulated by similar inductive networks in the two organisms. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV WOMENS & PERINATAL PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 56 TC 413 Z9 426 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 1995 VL 121 IS 10 BP 3163 EP 3174 PG 12 WC Developmental Biology SC Developmental Biology GA RZ756 UT WOS:A1995RZ75600004 PM 7588051 ER PT J AU VERGE, CF GIANANI, R YU, LP PIETROPAOLO, M SMITH, T JACKSON, RA SOELDNER, JS EISENBARTH, GS AF VERGE, CF GIANANI, R YU, LP PIETROPAOLO, M SMITH, T JACKSON, RA SOELDNER, JS EISENBARTH, GS TI LATE PROGRESSION TO DIABETES AND EVIDENCE FOR CHRONIC BETA-CELL AUTOIMMUNITY IN IDENTICAL-TWINS OF PATIENTS WITH TYPE-I DIABETES SO DIABETES LA English DT Article ID POSITIVE RELATIVES; MELLITUS; CONCORDANCE; ANTIBODIES; ASSAY; IDDM AB Previous studies suggest that after 6 years of discordance, identical twin pairs rarely become concordant for type I diabetes. With up to 39 years of follow-up from the onset of diabetes in the index twin, we determined how many discordant twins have evidence of beta-cell autoimmunity and how many develop overt diabetes. We longitudinally followed 23 pairs of identical twins (or triplets) that were selected from a total group of 30 pairs because they were discordant for type I diabetes when first ascertained. Seven developed diabetes after 3, 3, 7, 8, 9, 31, and 36 years of discordance. By survival analysis, the concordance after 10 years from the onset of diabetes in the index twin was estimated as 23% (95% confidence interval, 5-40%), increasing to 38% (95% confidence interval, 8-69%) after 31 years, Among 16 twins remaining nondiabetic at last follow-up (8-39 years of discordance), 12 were assessed with serial intravenous glucose tolerance tests and a total of 407 measurements by radioassay of antibodies against three defined autoantigens (glutamic acid decarboxylase, insulin, and the recently cloned molecule ICA512). Two-thirds (8 of 12) had evidence of beta-cell autoimmunity (persistently positive autoantibody levels) and/or first-phase insulin release less than the Ist percentile of control subjects, In summary, identical twins may develop diabetes after a prolonged period of discordance and approximately two-thirds of long-term discordant twins have evidence of persistent beta-cell autoimmunity and/or beta-cell damage, The concordance for beta-cell autoimmunity, therefore, is much higher than for overt diabetes, This suggests that additional environmental or non-Mendelian genetic factors or time are required for the development of type I diabetes. C1 UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABET,DENVER,CO 80262. JOSLIN DIABET CTR,BOSTON,MA 02215. UNIV CALIF DAVIS,DIV ENDOCRINOL & METAB,SACRAMENTO,CA 95817. FU NIDDK NIH HHS [DK-32083, DK-43279] NR 15 TC 79 Z9 81 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1995 VL 44 IS 10 BP 1176 EP 1179 DI 10.2337/diabetes.44.10.1176 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TD624 UT WOS:A1995TD62400007 PM 7556954 ER PT J AU SWEENEY, FP SICZKOWSKI, M DAVIES, JE QUINN, PA MCDONALD, J KROLEWSKI, B KROLEWSKI, AS NG, LL AF SWEENEY, FP SICZKOWSKI, M DAVIES, JE QUINN, PA MCDONALD, J KROLEWSKI, B KROLEWSKI, AS NG, LL TI PHOSPHORYLATION AND ACTIVITY OF NA+/H+ EXCHANGER ISOFORM-1 OF IMMORTALIZED LYMPHOBLASTS IN DIABETIC NEPHROPATHY SO DIABETES LA English DT Article ID SODIUM-LITHIUM COUNTERTRANSPORT; ANTIPORT ACTIVITY; OKADAIC ACID; RED-CELLS; HYPERTENSION; SUSCEPTIBILITY; PREDISPOSITION; MEMBRANE; DISEASE AB In both essential hypertension and diabetic nephropathy (DN), the ubiquitous cellular Na+/H+ exchanger (NHE) exhibits altered kinetics with increased transport activity, The mechanism for this phenotype and its dependence on the presence of serum are unknown, but increased lymphoblast NHE activity in DN has been attributed to a defect in post-translational processing of NHE-1 rather than an increased cellular exchanger number, Phosphorylation of NHE-1 has been proposed to play a role in its activation in a variety of cell models, We have examined, therefore, the role of NHE-1 phosphorylation and the effect of serum in determining the increased NHE-1 activity in lymphoblasts from patients with DN. Cells from these patients exhibited increased NHE activity in the presence and absence of fetal calf serum (range 42-59%, P < 0.005, analysis of variance) and an increased proliferation rate (P < 0.01) when compared with cells from both normoalbuminuric diabetic patients and nondiabetic control subjects, However, NHE-1 abundance was very similar among all groups in the presence and absence of serum, indicating that increased NHE activity in cells of nephropathy patients was due to an increased turnover number, This nephropathy phenotype was not accompanied by an increased net phosphorylation of NHE-1 in the presence or absence of serum, Our findings suggest that increased NHE-1 activity in cells of DN patients is independent of the presence of serum and is not attributable to altered NHE-1 phosphorylation, Additional post-translational mechanisms for activation of NHE-1, therefore, may be involved, C1 LEICESTER ROYAL INFIRM,DEPT MED & THERAPEUT,DEPT CLIN PHARMACOL,LEICESTER LE2 7LX,LEICS,ENGLAND. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. JOSLIN DIABET CTR,BOSTON,MA 02215. FU NIDDK NIH HHS [DK-41526, DK-36836]; Wellcome Trust NR 22 TC 11 Z9 12 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 1995 VL 44 IS 10 BP 1180 EP 1185 DI 10.2337/diabetes.44.10.1180 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TD624 UT WOS:A1995TD62400008 PM 7556955 ER PT J AU FOITZIK, T HOTZ, HG SCHMIDT, J KLAR, E WARSHAW, AL BUHR, HJ AF FOITZIK, T HOTZ, HG SCHMIDT, J KLAR, E WARSHAW, AL BUHR, HJ TI EFFECT OF MICROCIRCULATORY PERFUSION ON DISTRIBUTION OF TRYPSINOGEN ACTIVATION PEPTIDES IN ACUTE EXPERIMENTAL PANCREATITIS SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE ACUTE PANCREATITIS; EDEMATOUS PANCREATITIS; NECROTIZING PANCREATITIS; TRYPSINOGEN ACTIVATION PEPTIDES; MICROCIRCULATION; PANCREATIC BLOOD FLOW ID COMPUTED-TOMOGRAPHY; PREDICTION; ASSAY; MODEL; RAT AB Extraintestinal trypsinogen activation peptides (TAP) have been shown to correlate with severity of acute pancreatitis in humans as well as in various animal models. Ischemia superimposed on experimental pancreatitis, however, increases acinar cell injury without increasing TAP in plasma. We speculated that TAP generated in the pancreas might not reach the circulation in necrotizing pancreatitis due to decreased pancreatic perfusion. To test the hypothesis that generation of TAP in plasma is related to pancreatic perfusion and that plasma TAP may therefore underestimate acinar cell injury in necrotizing disease, we correlated TAP in pancreatic tissue and body fluids with capillary pancreatic blood flow in necrotizing and edematous pancreatitis. The ratio between necrosis and TAP in tissue was similar in both models; the ratio between TAP in plasma and tissue, however, was significantly lower in necrotizing pancreatitis, indicating that a certain amount of TAP generated in the pancreas did not reach the circulation. Decreased pancreatic perfusion found in necrotizing pancreatitis was consistent with this finding. Our data suggest that TAP in tissue is most reliable to indicate severity of acute pancreatitis, whereas plasma TAP may underestimate pancreatic injury in necrotizing disease due to decreased pancreatic perfusion. C1 UNIV HEIDELBERG,DEPT SURG,W-6900 HEIDELBERG,GERMANY. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP FOITZIK, T (reprint author), FREE UNIV BERLIN,KLINIKUM BENJAMIN FRANKLIN,DEPT SURG,HINDENBURGDAMM 30,D-12200 BERLIN,GERMANY. NR 17 TC 21 Z9 22 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 1995 VL 40 IS 10 BP 2184 EP 2188 DI 10.1007/BF02209003 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TE102 UT WOS:A1995TE10200015 PM 7587786 ER PT J AU RABINOWITZ, WM EDDINGTON, DK AF RABINOWITZ, WM EDDINGTON, DK TI EFFECTS OF CHANNEL-TO-ELECTRODE MAPPINGS ON SPEECH RECEPTION WITH THE INERAID COCHLEAR IMPLANT SO EAR AND HEARING LA English DT Article ID CONSONANT RECOGNITION; DEAF SUBJECTS; DESIGN AB Objective: Research was conducted to assess multi-channel saliency with the Ineraid cochlear prosthesis. The goal was to determine whether tonotopically ordered stimulation benefits speech reception. Design: In a single high-performing subject, changes in speech reception were studied during two dramatic alterations to the normal (tonotopic) mapping between the sound-processor's four filter channels and the intracochlear electrode array: In one alteration, the four filter outputs were summed and delivered to one electrode; this single channel mapping was worn for 7 days. Tu another alteration, the four filter outputs were connected in reverse tonotopic order to four intracochlear electrodes; this reversed mapping was worn for 3 days. Results: When using the implant in conjunction with speechreading, all three mappings provided large gains over speechreading alone on the recognition of words in sentences. When using the implant alone (without speechreading), tests of consonant and vowel recognition, and the recognition of words in isolation and in sentences all showed substantial decreases in performance across the three mapping conditions: normal > single-channel > reversed. The patterns of segmental confusions and the relations among scores on different tests were highly consistent. Finally, the performance with the altered mappings was, in some ways, remarkably good. With the single-channel mapping, 15% word recognition was obtained, much less than the 54% obtained with the normal mapping, but demonstrative of some open-set speech reception. With the reversed mapping, high levels of consonantal voicing and manner information were received, indicating good reception of time-intensity cues, but open-set word recognition was near zero. Conclusions: Despite the extensive spread of current associated with monopolar intracochlear stimulation, the Ineraid electrode array affords a degree of perceptual selectivity that substantially aids speech reception. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RABINOWITZ, WM (reprint author), MIT,ROOM 36-789,77 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. RI Imhof, Margarete/F-8471-2011 FU NIDCD NIH HHS [P01 DC00361] NR 30 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD OCT PY 1995 VL 16 IS 5 BP 450 EP 458 DI 10.1097/00003446-199510000-00002 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA RZ503 UT WOS:A1995RZ50300002 PM 8654900 ER PT J AU LEE, SK GOLDRING, SR LORENZO, JA AF LEE, SK GOLDRING, SR LORENZO, JA TI EXPRESSION OF THE CALCITONIN RECEPTOR IN BONE-MARROW CELL-CULTURES AND IN BONE - A SPECIFIC MARKER OF THE DIFFERENTIATED OSTEOCLAST THAT IS REGULATED BY CALCITONIN SO ENDOCRINOLOGY LA English DT Article ID MULTINUCLEATED CELLS; PARATHYROID-HORMONE; RAT OSTEOCLASTS; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; OSTEOTROPIC HORMONES; ADENYLATE-CYCLASE; HUMAN-LYMPHOCYTES; BINDING-SITES; MOUSE; RESORPTION AB We studied the temporal sequence of osteoclast (OC) differentiation from precursor cells in murine marrow cultures. Two markers of the OC phenotype, calcitonin (CT) receptor (CTR) and tartrate resistant acid phosphatase (TRAP), were assessed. Marrow cells from C57BL/6 mice were cultured for 3, 5, 7, and 9 days with or without 1,25-(OH)(2) vitamin D-3 (10(-8) M). In controls only small numbers of osteoclastic multinucleated cells (MNCs) formed per well (<15 per well). In contrast, 1,25(OH)(2)D-3 strongly stimulated MNC formation (>80 per well on day 7). Messenger RNA (mRNA) for TRAP was detectable by reverse transcription-polymerase chain reaction amplification in both control and 1,25-(OH)(2)D-3 treated groups at all times. However, TRAP mRNA was detectable in MNCs by the less sensitive in situ hybridization only on days 5, 7, and 9 and only in 1,25-(OH)(2)D-3 treated cells. In control cultures, CTR mRNA was present on day 3 only in nonadherent cells and was not present in adherent cells (where MNCs formed) at any time point. In 1,25(OH)(2)D-3 treated cultures CTR mRNA was detectable in nonadherent cells on day 3 and in adherent cells on day 5 and thereafter. Peak levels of CTR mRNA were seen in adherent cells on day 7 (15-fold more than day 5 and 4-fold more than day 9). CT (10(-7) M) treatment of 7 day cultures, which had been stimulated to express the osteoclastic phenotype, caused a marked decrease in CTR mRNA expression at 24 h. There was no effect of CT treatment on CTR mRNA expression at 3 h or on TRAP mRNA expression at 3 or 24 h. In neonatal mouse calvaria cultures, CTR mRNA expression was constitutively present and was markedly decreased by 48 h of CT treatment. Similarly, bone resorption in these cultures was inhibited at 24 h by CT treatment, but at 48 and 72 h there was escape from the inhibitory effects of CT on resorption. In the marrow cultures, MNCs were greater than 98% positive for [I-125]-salmon calcitonin (sCT) binding and this binding was completely competed away by excess cold sCT (10(-7) M). All primary isolated osteoclasts from 1- to 3-day-old mouse long bones exhibited [I-125]-sCT binding and TRAP activity and were strongly positive for CTR and TRAP mRNA. by in situ hybridization. Both MNCs that formed in bone marrow cultures and isolated primary osteoclasts formed resorption pits on bone slices. These studies demonstrate that CTR and TRAP functional activity and mRNA are expressed in marrow cultures that were induced to differentiate into OC by 1,25-(OH)(2)D-3. The expression of CT receptor mRNA was coincident with the development of the osteoclast-like phenotype in the marrow cultures and was more specific than expression of TRAP mRNA. Treatment of either marrow or bane organ cultures with CT down-regulated the expression of the CTR mRNA. Hence, calcitonin-induced down-regulation of CTR mRNA and the resultant decrease in functional CTR activity provide a mechanism for the phenomenon of CT escape. C1 VET AFFAIRS MED CTR,NEWINGTON,CT 06111. UNIV CONNECTICUT,CTR HLTH,FARMINGTON,CT 06030. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02114. FU NIAMS NIH HHS [AR-03564, AR-42362]; NIDDK NIH HHS [DK-46773] NR 56 TC 80 Z9 82 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1995 VL 136 IS 10 BP 4572 EP 4581 DI 10.1210/en.136.10.4572 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RW031 UT WOS:A1995RW03100055 PM 7664679 ER PT J AU REEVES, SA SINHA, B BAUR, I REINHOLD, D HARSH, G AF REEVES, SA SINHA, B BAUR, I REINHOLD, D HARSH, G TI AN ALTERNATIVE ROLE FOR THE SRC-HOMOLOGY-DOMAIN-CONTAINING PHOSPHOTYROSINE PHOSPHATASE (SH-PTP2) IN REGULATING EPIDERMAL-GROWTH-FACTOR-DEPENDENT CELL-GROWTH SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE SRC-HOMOLOGY-2-DOMAIN-CONTAINING PHOSPHOTYROSINE PHOSPHATASE (SH-PTP2) GROWTH INHIBITION; TYROSINE PHOSPHATASE; SRC-HOMOLOGY 2; EPIDERMAL GROWTH FACTOR ID PROTEIN-TYROSINE-PHOSPHATASE; SIGNAL TRANSDUCTION; SEQUENCE SIMILARITY; SH2 DOMAIN; MOLECULAR-CLONING; RECEPTOR; KINASES; CORKSCREW; PHOSPHORYLATION; PROLIFERATION AB The association of the src homology 2 (SH2) domain-containing tyrosine phosphatase (SH-PTP2) with the activated epidermal growth factor (EGF) and platelet-derived growth factor receptors, as well as the insulin receptor substrate 1 and growth-factor-receptor-bound protein 2 and its intrinsic tyrosine phosphatase activity suggests an important role for this phosphatase in signal transduction. Previous studies have shown a positive role for SH-PTP2 in growth-factor-mediated cell signaling. We show here that SH-PTP2 can also function to negatively regulate EGF-mediated signal transduction in the human glioma cell line SNB19. We demonstrate this by showing that, in SNB19 cells, which lack the ability to proliferate in response to EGF but retain the ability to bind EGF and also activate the EGF receptor as well as allow for the association of SH-PTP2 with the phosphorylated receptor, stable overexpression of an interfering SH-PTP2 mutant can restore the ability of these cells to proliferate in response to EGF. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RP REEVES, SA (reprint author), MASSACHUSETTS GEN HOSP,CTR NEUROSCI,MOLEC NEUROONCOL LAB,BOSTON,MA 02129, USA. NR 39 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD OCT 1 PY 1995 VL 233 IS 1 BP 55 EP 61 DI 10.1111/j.1432-1033.1995.055_1.x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RZ497 UT WOS:A1995RZ49700008 PM 7588774 ER PT J AU HUNCHAREK, M AF HUNCHAREK, M TI GENETIC-FACTORS IN THE ETIOLOGY OF MALIGNANT MESOTHELIOMA SO EUROPEAN JOURNAL OF CANCER LA English DT Review ID CELL LUNG-CANCER; FAMILIAL MESOTHELIOMA; FLOW-CYTOMETRY; PROGNOSTIC-SIGNIFICANCE; ASBESTOS EXPOSURE; P53 GENE; LINES; DNA; EXPRESSION; ABNORMALITIES RP HUNCHAREK, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 66 TC 29 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 1995 VL 31A IS 11 BP 1741 EP 1747 DI 10.1016/0959-8049(95)00365-P PG 7 WC Oncology SC Oncology GA TF390 UT WOS:A1995TF39000007 PM 8541092 ER PT J AU GOLDHIRSCH, A WOOD, WC SENN, HJ GLICK, JH GELBER, RD AF GOLDHIRSCH, A WOOD, WC SENN, HJ GLICK, JH GELBER, RD TI INTERNATIONAL CONSENSUS PANEL ON THE TREATMENT OF PRIMARY BREAST-CANCER SO EUROPEAN JOURNAL OF CANCER LA English DT Review ID SURGICAL ADJUVANT BREAST; TAMOXIFEN; THERAPY; CHEMOTHERAPY; TUMORS C1 EMORY UNIV,SCH MED,DEPT SURG,ATLANTA,GA 30322. KANTONSSPITAL,MED KLIN C,CH-9007 ST GALLEN,SWITZERLAND. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. DANA FARBER CANC INST,BOSTON,MA 02115. RP GOLDHIRSCH, A (reprint author), OSPED CIVICO,INT BREAST CANC STUDY GRP,CH-6900 LUGANO,SWITZERLAND. NR 15 TC 43 Z9 43 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD OCT PY 1995 VL 31A IS 11 BP 1754 EP 1759 DI 10.1016/0959-8049(95)00479-3 PG 6 WC Oncology SC Oncology GA TF390 UT WOS:A1995TF39000009 PM 8541094 ER PT J AU AGEMATSU, K KOBATA, T YANG, FC NAKAZAWA, T FUKUSHIMA, K KITAHARA, M MORI, T SUGITA, K MORIMOTO, C KOMIYAMA, A AF AGEMATSU, K KOBATA, T YANG, FC NAKAZAWA, T FUKUSHIMA, K KITAHARA, M MORI, T SUGITA, K MORIMOTO, C KOMIYAMA, A TI CD27/CD70 INTERACTION DIRECTLY DRIVES B-CELL IGG AND IGM SYNTHESIS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD27; CD70; IMMUNOGLOBULIN ID TUMOR-NECROSIS-FACTOR; CD40 LIGAND; CD27; ACTIVATION; EXPRESSION; ANTIGEN; FAMILY; INVITRO; MEMBER AB CD27 is a T cell activation antigen expressed on a majority of peripheral blood T cells. CD27 is also expressed on a subpopulation of human B cells, and it is reported that CD27(+) B cells secrete both IgG and IgM. CD70, a ligand for CD27, is expressed on activated T and B cells, suggesting an interaction between T and B cells via CD27/CD70 ligation. Here, we analyze B cell immunoglobulin synthesis using a CD70 transfectant and present functional data showing that B cells secrete large amounts of IgG and IgM as a result of the CD27/CD70 interaction. A flow cytometric analysis showed that CD27 expression was increased and CD70 was expressed on tonsillar and peripheral blood B cells after activation with Staphylococcus aureus Cowan strain (SAC) plus interleukin (IL-2). In addition, the proliferation of B cells was enhanced mildly by the addition of CD70 transfectant, and its proliferation was blocked by anti-CD70 mAb. More importantly, the CD70 transfectant enhanced IgG and IgM production by purified B cells greatly in the presence of SAC plus IL-2. The enhancement was completely blocked by the addition of either anti-CD70 mAb or anti-CD27 mAb. Strongly suggesting that the interaction of CD27 with its ligand, CD70, on B cells plays an important role in B cell growth and differentiation to produce IgG and IgM. C1 SHINSHU UNIV,SCH MED,DEPT PEDIAT,MATSUMOTO,NAGANO 390,JAPAN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA. YAMANASKI MED COLL,DEPT PEDIAT,KOFU,YAMANASHI,JAPAN. NR 26 TC 70 Z9 70 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 1995 VL 25 IS 10 BP 2825 EP 2829 DI 10.1002/eji.1830251017 PG 5 WC Immunology SC Immunology GA TB371 UT WOS:A1995TB37100016 PM 7589078 ER PT J AU RENNARD, SI WEISS, S WOOLCOCK, AJ LERTZMAN, M PAOLETTI, P BILLO, NE DONNER, C HENNINGFIELD, JE MOXHAM, J RIGOTTI, N SAMET, J SNELL, J SOFFER, A BREELING, JL AF RENNARD, SI WEISS, S WOOLCOCK, AJ LERTZMAN, M PAOLETTI, P BILLO, NE DONNER, C HENNINGFIELD, JE MOXHAM, J RIGOTTI, N SAMET, J SNELL, J SOFFER, A BREELING, JL TI SMOKING AND HEALTH - A PHYSICIANS RESPONSIBILITY - A STATEMENT OF THE JOINT COMMITTEE ON SMOKING AND HEALTH SO EUROPEAN RESPIRATORY JOURNAL LA English DT Editorial Material ID TOBACCO; MORTALITY; CESSATION; NICOTINE C1 BRIGHAM & WOMENS HOSP,CHANNING LAB,BOSTON,MA 02115. UNIV SYDNEY,SYDNEY,NSW 2006,AUSTRALIA. CNR,INST CLIN PHYSIOL,I-56100 PISA,ITALY. IUATLD,PARIS,FRANCE. VERUNO MED CTR,VERUNO,ITALY. NIDA,BALTIMORE,MD. UNIV LONDON KINGS COLL,SCH MED & DENT,LONDON WC2R 2LS,ENGLAND. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. VANDERBILT CLIN,NASHVILLE,TN. ACCP,NORTHBROOK,IL. RP RENNARD, SI (reprint author), UNIV NEBRASKA,MED CTR,OMAHA,NE 68182, USA. NR 15 TC 11 Z9 11 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD OCT PY 1995 VL 8 IS 10 BP 1808 EP 1811 PG 4 WC Respiratory System SC Respiratory System GA TG619 UT WOS:A1995TG61900033 ER PT J AU HU, LK HASAN, T GRAGOUDAS, ES YOUNG, LHY AF HU, LK HASAN, T GRAGOUDAS, ES YOUNG, LHY TI PHOTOIMMUNOTHERAPY OF HUMAN UVEAL MELANOMA-CELLS SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE UVEAL MELANOMA CELLS; PHOTOIMMUNOTHERAPY; MELANOMA-REACTIVE MONOCLONAL ANTIBODY ID PROTON-BEAM IRRADIATION; ANTIBODY-TARGETED PHOTOLYSIS; COBALT PLAQUE RADIOTHERAPY; MONOCLONAL-ANTIBODIES; PHOTODYNAMIC THERAPY; MALIGNANT MELANOMAS; OCULAR MELANOMA; CARCINOMA; SURVIVAL; RADIOIMMUNOSCINTIGRAPHY AB To examine whether tumor-reactive monoclonal antibodies can be used to enhance photodestruction of human uveal melanoma cells, we conjugated photosensitizer chlorin e(6) monoethylenediamine monoamide (CMA) with a melanoma-reactive monoclonal antibody IG12 and evaluated the effectiveness of this immunoconjugate (IC) in the destruction of OCM431 human uveal melanoma cells in vitro. RPMI1846 melanoma cells do not react with IC and were used as non-target cells. For control, target and non-target cells were treated with IC or light alone. The effects of IC and free CMA in the destruction of melanoma cells were compared. Cell survival was assessed by a colorimetric assay using tetrazolium salt MTT. Target (OCM431) cells preincubated with IC and irradiated with 5-40 J cm(-2) showed light dose-dependent decrease in cell survival. At 40 J cm(-2), OCM431 cells preincubated with IC showed only 6 +/- 1.4% viability. Under same treatment, non-target (RPMI1846) cells showed much less phototoxicity; cell survival was 54 +/- 2.1%. Treatment with free CMA and light at 40 J cm(-2) showed similar phototoxicity to both target and non-target cells, with cell survival being 24.3 +/- 3.5% and 23.7 +/- 1.5%, respectively. These results show that our IC is effective in causing photodestruction of human uveal melanoma cells in vitro. The phototoxicity is selective and more potent than free CMA. (C) 1995 Academic Press Limited C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LAB,BOSTON,MA 02114. FU NIAMS NIH HHS [R01 AR40352] NR 46 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 1995 VL 61 IS 4 BP 385 EP 391 PG 7 WC Ophthalmology SC Ophthalmology GA RZ675 UT WOS:A1995RZ67500001 PM 8549679 ER PT J AU CHENG, HM CHENG, FY TANAKA, GH XIONG, J PFLEIDERER, B AF CHENG, HM CHENG, FY TANAKA, GH XIONG, J PFLEIDERER, B TI MANIPULATING RAT LENS GLUCOSE-METABOLISM WITH EXOGENOUS SUBSTRATES SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE MANNOSE; PYRUVATE; SORBITOL PATHWAY; DIABETES; RAT LENS; NMR SPECTROSCOPY; OXYGEN CONSUMPTION ID ALDOSE REDUCTASE INHIBITOR; PHOSPHATE-METABOLISM; DIABETIC RATS; PREVENTION; IDENTIFICATION; 3-PHOSPHATE; SORBINIL; NERVE AB Diabetic lens glucose metabolism in vivo can be altered by a number of exogenous substrates. We have chosen two, one a glucose epimer (mannose) and the other a glycolytic intermediate (pyruvate), to demonstrate the possibility of this approach. D(+)-Mannose is a D(+)-glucose epimer but in lenses incubated in 35.5 mM mannose, no mannitol (the sorbitol equivalent) was detected, while both lactate production and P-31 profile appeared normal. Mannose therefore is a good glucose substitute causing no polyol formation. Mannose metabolism in the rat lens in vivo was then examined. Diabetic rats fed mannose-enriched diet over a period of 14 days showed retardation of changes in P-31 metabolites, specifically the levels of phosphorylcholine and glycerophosphorylcholine, suggesting a protective effect. Rat lenses incubated in 35.5 mM glucose in the presence of 5 mM pyruvate (pyr) showed 50% lower sorbitol than without pyr. With 5 mM pyr in the drinking water, i.e. pretreatment in vivo during a 3-day diabetes induction period, the diabetic rat lens accumulated acetate and alanine when incubated in the presence of pyr. The decrease in sorbitol was most likely due to a lower glucose nux rather than an increased polyol dehydrogenase activity, Increasing glucose concentration from 5.5 to 35.5 mM or provision of exogenous pyr both caused an intermediate increase in O-2 consumption in the normal lens; a maximal activity was reached with both 35.5 mM glucose and 5 mM pyruvate in the incubating medium. In the diabetic lens, O-2 consumption could reach the intermediate but not the maximal level. Dietary pyr pre-treatment also prevented normal and diabetic lenses from maximal pyr-stimulated O-2 consumption. The NMR and O-2 consumption data together indicated activation of alanine dehydrogenase and saturation of Krebs cycle. It appears that dietary supplement of mannose can preserve P-31 membrane metabolites in the diabetic lens. Mannose can be used in conjunction with hypoglycemic therapy for the management of diabetic cataract. In addition, pyruvate may be effective in enhancing lens energy metabolism and lower sorbitol production. (C) 1995 Academic Press Limited C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR NMR,BOSTON,MA 02129. RP CHENG, HM (reprint author), HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,NMR RES,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY04424] NR 24 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 1995 VL 61 IS 4 BP 479 EP 486 DI 10.1016/S0014-4835(05)80143-5 PG 8 WC Ophthalmology SC Ophthalmology GA RZ675 UT WOS:A1995RZ67500011 PM 8549689 ER PT J AU DINSMORE, JH DEACON, T PAKZABAN, P RATLIFF, J ISACSON, O AF DINSMORE, JH DEACON, T PAKZABAN, P RATLIFF, J ISACSON, O TI NEURONS DIFFERENTIATED IN-VITRO FROM PLURIPOTENT EMBRYONIC STEM-CELLS FOR CNS TRANSPLANTATION - IN-VITRO CHARACTERIZATION AND TRANSPLANTATION INTO RODENTS SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 DIACRIN INC,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02114. MCLEAN HOSP,NEUROREGENERAT LAB,BELMONT,MA 02178. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1995 VL 135 IS 2 BP 163 EP 163 PG 1 WC Neurosciences SC Neurosciences & Neurology GA TC202 UT WOS:A1995TC20200023 ER PT J AU GALPERN, WR BURNS, LH DEACON, TW TATTER, SB DINSMORE, J ISACSON, O AF GALPERN, WR BURNS, LH DEACON, TW TATTER, SB DINSMORE, J ISACSON, O TI XENOTRANSPLANTATION AND ANTIGEN MASKING OF FETAL PORCINE VENTRAL MESENCEPHALON IN A RAT MODEL OF PARKINSONS-DISEASE SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MCLEAN HOSP,NEUROREGENERAT LAB,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01605. DIACRIN INC,BOSTON,MA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1995 VL 135 IS 2 BP 164 EP 164 PG 1 WC Neurosciences SC Neurosciences & Neurology GA TC202 UT WOS:A1995TC20200032 ER PT J AU TODD, R MCBRIDE, J TSUJI, T DONOFF, RB NAGAI, M CHOU, MY CHIANG, T WONG, DTW AF TODD, R MCBRIDE, J TSUJI, T DONOFF, RB NAGAI, M CHOU, MY CHIANG, T WONG, DTW TI DELETED IN ORAL CANCER-1 (DOC-1), A NOVEL ORAL TUMOR-SUPPRESSOR GENE SO FASEB JOURNAL LA English DT Article DE CHEMICAL CARCINOGENS; SUBTRACTIVE HYBRIDIZATION ID HUMAN CHORIONIC-GONADOTROPIN; POUCH KERATINOCYTES; DOWN-REGULATION; HA-RAS; CELLS; EXPRESSION; ONCOGENES; CARCINOGENESIS; ANGIOGENESIS; CARCINOMA AB We have identified, isolated, and partially characterized doc-1, a novel cDNA sequence whose activity is consistent with a suppressor of hamster oral carcinogenesis. Doc-1 is an evolutionarily conserved gene exhibiting loss of heterozygosity and marked reduction in expression in malignant hamster oral keratinocytes. The full-length doc-1 cDNA encodes an 87 amino acid product that shows a significant homology to one of the seven novel genes induced in mouse fibroblasts by TNF-alpha. Transfection of the full-length doc-1 cDNA into malignant hamster oral keratinocytes alters the behavior of the recipients in terms of morphology, growth rate, and anchorage-independent growth, suggesting reversion of transformation phenotypes. We propose that doc-1 is a novel tumor suppressor gene in oral cancer development. C1 HARVARD UNIV,SCH DENT MED,DEPT ORAL MED & DIAGNOST SCI,DIV ORAL PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. FU NIDCR NIH HHS [DE-10208, DE-00275, DE-08680] NR 54 TC 69 Z9 76 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 1995 VL 9 IS 13 BP 1362 EP 1370 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TA370 UT WOS:A1995TA37000016 PM 7557027 ER PT J AU OKEEFE, RJ ODONNELL, RJ TEMPLE, HT SCULLY, SP MANKIN, HJ AF OKEEFE, RJ ODONNELL, RJ TEMPLE, HT SCULLY, SP MANKIN, HJ TI GIANT-CELL TUMOR OF BONE IN THE FOOT AND ANKLE SO FOOT & ANKLE INTERNATIONAL LA English DT Article AB Giant cell tumor of bone has been shown to behave more aggressively when located in the wrist and hand. Although nearly 4% of giant cell tumors arise in the foot and ankle, biological features specific to this location have not been identified, In our experience with more than 300 cases of giant cell tumor, 12 arose in the foot and ankle and were followed for more than 2 years. These included nine females and three males ranging in age from 15 to 52 years (mean age, 29.5 years), All patients presented with pain of 5.0 months' mean duration and 9 of 12 tumors demonstrated aggressive radiographic features, including bone erosion and destruction; five had either invasion of a joint or a soft tissue mass present, Unlike the hand, where metacarpal and phalangeal lesions are common, no tumors arose in the forefoot and nine of the tumors were present in the ankle region. Four patients were treated with resection (no recurrence), two with curettage and cement packing (one recurrence), and six with curettage and autologous bone graft (two recurrences), which resulted in an overall recurrence rate of 25%. None of the recurrent tumors have returned after additional treatment, which consisted of curettage and cement packing in two cases and resection in one case, Five tumors (four primary, one recurrent) were treated with local resection and reconstruction with no major complications and with no amputations performed. Thus, giant cell tumors of the foot and ankle can be treated with local procedures, which result in recurrence rates similar to those found in more common locations. C1 MASSACHUSETTS GEN HOSP,OTHOPAED ONCOL UNIT,BOSTON,MA 02114. NR 0 TC 18 Z9 19 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD OCT PY 1995 VL 16 IS 10 BP 617 EP 623 PG 7 WC Orthopedics SC Orthopedics GA TA665 UT WOS:A1995TA66500007 PM 8574373 ER PT J AU TAMIYA, T WEI, MX CHASE, M ONO, Y LEE, F BREAKEFIELD, XO CHIOCCA, EA AF TAMIYA, T WEI, MX CHASE, M ONO, Y LEE, F BREAKEFIELD, XO CHIOCCA, EA TI TRANSGENE INHERITANCE AND RETROVIRAL INFECTION CONTRIBUTE TO THE EFFICIENCY OF GENE-EXPRESSION IN SOLID TUMORS INOCULATED WITH RETROVIRAL VECTOR PRODUCER CELLS SO GENE THERAPY LA English DT Article DE GENE TRANSFER; GENE THERAPY; RETROVIRUS VECTORS; BRAIN TUMORS; CANCER ID BRAIN-TUMORS; NERVOUS-SYSTEM; GLIOMA-CELLS; CULTURE; INVIVO AB One strategy to achieve efficient gene delivery into brain tumors employs the stereotactic implantation of fibroblasts that express a foreign gene and produce a retroviral vector bearing that gene. Another method involves the grafting of fibroblasts genetically engineered to produce a foreign gene product of interest. It is not clear to what extent retrovirus production in vivo provides an advantage over the grafting of genetically engineered cells for the purpose of achieving transgene expression. These two methods of gene delivery were compared in vivo by using the following cell lines: CRIP-MFGd-LacZ cells, which express the lacZ gene and produce retrovirus vectors that bear this gene, and CRIP-LacZ cells, which express the lacZ gene, but do not produce retrovirus. Gene delivery was assessed in C6 gliomas established in the right frontal lobe of athymic mice. CRIP-MFG-LacZ or CRIP-LacZ cells were inoculated stereotactically into these tumors. When CRIP-MFG-LacZ cells were used, a relatively elevated level of lacZ gene expression was present in cells scattered throughout the tumor. Using a computerized imaging system, this expression occurred in approximately 10% of the tumor area at 1 week, 42% at 2 weeks, and 32% at 3 weeks. In contrast, with CRIP-LacZ cells, lacZ gene expression was much weaker and occurred in a more focal area within the tumor. This expression occupied approximately 5% of the tumor area at 1 and 2 weeks and had almost disappeared at 3 weeks. In both cases there was no notable expression of the transgene in normal brain cells. In conclusion, transgene expression in brain tumors was achieved in more cells, at higher levels, and the longer time periods with retroviral vector-producing cells than with genetically engineered fibroblasts. This efficiency of gene delivery likely results from direct in situ delivery of the transgene to tumor cells with subsequent inheritance of the reporter gene to progeny tumor cells. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,NEUROSURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NINDS NIH HHS [NS 24279-08] NR 15 TC 31 Z9 31 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 1995 VL 2 IS 8 BP 531 EP 538 PG 8 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 RY657 UT WOS:A1995RY65700004 PM 8593603 ER PT J AU TROFATTER, JA LONG, KR MURRELL, JR STOTLER, CJ GUSELLA, JF BUCKLER, AJ AF TROFATTER, JA LONG, KR MURRELL, JR STOTLER, CJ GUSELLA, JF BUCKLER, AJ TI AN EXPRESSION-INDEPENDENT CATALOG OF GENES FROM HUMAN-CHROMOSOME 22 SO GENOME RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; SOMATIC-CELL HYBRIDS; DROSOPHILA-MELANOGASTER; TRANSCRIBED SEQUENCES; EXON AMPLIFICATION; DNA FRAGMENTS; HUMAN GENOME; CANDIDATE; PROTEIN; HETEROCHROMATIN AB To accomplish large-scale identification of genes from a single human chromosome, exon amplification was applied to large pools of clones from a flow-sorted human chromosome 22 cosmid library. Sequence analysis of more than one-third of the 6400 cloned products identified 35% of the known genes previously localized to this chromosome, as well as several unmapped genes and randomly sequenced cDNAs. Among the more interesting sequence similarities are those that represent novel human genes that are related to others with known or putative functions, such as one exon from a gene that may represent the human homolog of Drosophila Polycomb. It is anticipated that sequences From at least half of the genes residing on chromosome 22 are contained within this exon library. This approach is expected to facilitate fine-structure physical and transcription mapping of human chromosomes, and accelerate the process of disease gene identification. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, MOLEC NEUROGENET UNIT, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, DEPT GENET, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. FU NHGRI NIH HHS [HG00169, HG00672] NR 40 TC 25 Z9 25 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD OCT PY 1995 VL 5 IS 3 BP 214 EP 224 DI 10.1101/gr.5.3.214 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TF348 UT WOS:A1995TF34800002 PM 8593609 ER PT J AU HISNANICK, JJ CODDINGTON, DA AF HISNANICK, JJ CODDINGTON, DA TI MEASURING HUMAN BETTERMENT THROUGH AVOIDABLE MORTALITY - A CASE FOR UNIVERSAL HEALTH-CARE IN THE USA SO HEALTH POLICY LA English DT Article DE AVOIDABLE MORTALITY; HEALTH CARE REFORM ID MEDICAL INTERVENTION; SOCIAL INEQUITIES; SERVICES; QUALITY; TRENDS; SWEDEN AB The USA system of health care has begun a monumental change that will affect everyone, irrespective of their socioeconomic status, professional status or pre-existing health insurance status, Whatever type of plan is finally implemented through the legislative process, there will need to be a way to evaluate its success (or failure). One way to evaluate the plan's effectiveness is through its impact on human betterment as viewed by a reduction in 'avoidable mortality' for those most in need of health care; the poor and uninsured. For one USA minority population, universal health care has improved human betterment by reducing avoidable mortality, even in the face of a severe burden of poverty. C1 US DEPT VET AFFAIRS,NATL CTR VET ANAL & STAT 008C12,WASHINGTON,DC 20420. GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,DEPT GEN PEDIAT,WASHINGTON,DC 20001. RP HISNANICK, JJ (reprint author), US DEPT VET AFFAIRS,NATL CTR VET ANAL & STAT 008C12,810 VERMONT AVE NW,WASHINGTON,DC 20420, USA. NR 32 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8510 J9 HEALTH POLICY JI Health Policy PD OCT PY 1995 VL 34 IS 1 BP 9 EP 19 DI 10.1016/0168-8510(94)00715-Q PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA TA314 UT WOS:A1995TA31400002 PM 10151967 ER PT J AU MAGOVCEVIC, I KHETARPAL, U BIEBER, FR MORTON, CC AF MAGOVCEVIC, I KHETARPAL, U BIEBER, FR MORTON, CC TI GNAZ IN HUMAN FETAL COCHLEA - EXPRESSION, LOCALIZATION, AND POTENTIAL ROLE IN INNER-EAR FUNCTION SO HEARING RESEARCH LA English DT Article DE G PROTEIN; HYBRIDIZATION IN SITU; IMMUNOHISTOCHEMISTRY; COCHLEAR IONIC BALANCE ID PURIFIED MUSCARINIC RECEPTORS; PROTEIN ALPHA-SUBUNIT; GTP-BINDING PROTEIN; ADENYLATE-CYCLASE; STRIA VASCULARIS; MOLECULAR MECHANISM; CYCLIC-AMP; MOUSE; NA+,K+-ATPASE; FAMILY AB Dissociation of an activated alpha-subunit from the beta-gamma complex directly regulates secondary messenger proteins. To address the potential role of G proteins expressed in human fetal cochlea, degenerate oligonucleotide primers corresponding to the 3'-end of the conserved region of a-subunits were used for polymerase chain reaction amplification of reverse-transcribed total human fetal cochlear mRNAs; GNAZ and GNAQ were isolated. These two G proteins are unique among the G-protein family because they lack a typical pertussis modification site. GNAZ is expressed in high levels in neural tissue while GNAQ is ubiquitously expressed. We characterized GNAZ expression using Northern blots, tissue in-situ hybridization and immunohistochemistry techniques to elucidate the potential role of this protein in inner ear function. Our data suggest that GNAZ may play a role in maintaining the ionic balance of perilymphatic and endolymphatic cochlear fluids. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. FU NHLBI NIH HHS [HLO7627]; NIDCD NIH HHS [DC00871] NR 48 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 1995 VL 90 IS 1-2 BP 55 EP 64 DI 10.1016/0378-5955(95)00146-8 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA TK343 UT WOS:A1995TK34300006 PM 8975005 ER PT J AU LIBERMAN, MC GAO, WY AF LIBERMAN, MC GAO, WY TI CHRONIC COCHLEAR DE-EFFERENTATION AND SUSCEPTIBILITY TO PERMANENT ACOUSTIC INJURY SO HEARING RESEARCH LA English DT Article DE OLIVOCOCHLEAR; EFFERENT; OUTER HAIR CELL; COCHLEA; ACOUSTIC TRAUMA; SLOW EFFECT ID CROSSED OLIVOCOCHLEAR BUNDLE; TEMPORARY THRESHOLD SHIFTS; SUPERIOR OLIVARY COMPLEX; GUINEA-PIG COCHLEA; IMMUNOELECTRON MICROSCOPY; ELECTRICAL-STIMULATION; HORSERADISH-PEROXIDASE; AUDITORY-SENSITIVITY; MEDIAL ZONES; NEURONS AB The question of whether olivocochlear (OC) efferent feedback can decrease permanent damage from acoustic overexposure was investigated by comparing the chronic threshold shifts and cochlear histopathology in guinea pigs either surgically de-efferented or sham-operated and then exposed (awake and unrestrained) to a 109- or 112-dB narrow-band noise centered at 10 kHz for 2 h. Threshold shifts were estimated using compound action potentials; hair cell loss and stereocilia condition were evaluated via light-microscopic examination of plastic-embedded surface preparations, and the degree of de-efferentation was assessed by measuring OC fascicles in the tunnel of Corti. Among animals exposed to 109-dB noise, the mean permanent threshold shift (PTS) was less than 25 dB, and there were no significant differences between normal and de-efferented animals with respect to either physiological or histological measures of acoustic injury. Among animals exposed to 112 dB, the mean peak PTS was roughly 50 dB. There was a small (but statistically significant) increase in PTS for de-efferented animals, especially at frequencies above the region of peak threshold shift; however, the patterns of hair cell loss and stereocilia damage were statistically indistinguishable. Thus, for these particular exposure conditions, sound-evoked activity in the OC system does not play a major protective role in the auditory periphery, except perhaps for the extreme basal regions of the cochlea. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. HARVARD UNIV,MIT,DIV HLTH SCI TECHNOL,BOSTON,MA 02114. RP LIBERMAN, MC (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC 000188] NR 39 TC 57 Z9 57 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 1995 VL 90 IS 1-2 BP 158 EP 168 DI 10.1016/0378-5955(95)00160-2 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA TK343 UT WOS:A1995TK34300017 PM 8974993 ER PT J AU ZIMMERMANN, CE BURGESS, BJ NADOL, JB AF ZIMMERMANN, CE BURGESS, BJ NADOL, JB TI PATTERNS OF DEGENERATION IN THE HUMAN COCHLEAR NERVE SO HEARING RESEARCH LA English DT Article DE NEURAL DEGENERATION; SPIRAL GANGLION; SENSORINEURAL HEARING LOSS ID SENSORINEURAL HEARING-LOSS; SPIRAL GANGLION-CELLS; RETROGRADE DEGENERATION; NEURAL DEGENERATION; AUDITORY-NERVE; PATHOLOGY; DEAFNESS; IMPLANTATION; NEURONS; CATS AB The patterns of neural degeneration of the spiral ganglion were studied in 12 human pathologic specimens and 2 normal neonatal specimens. Morphometric analysis of spiral ganglion cells included the maximum cross-sectional areas of both large (type 1) and small (type II) spiral ganglion cells. The organ of Corti in segments corresponding to the spiral ganglion, was evaluated for the presence or absence of inner (IHC) and outer (OHC) hair cells and supporting cells. The relationship between degeneration of spiral ganglion cells and degeneration in the organ of Corti, the age, sex, duration of deafness, cochlear location and delay between death and fixation was evaluated statistically. Both primary and secondary degeneration of the spiral ganglion were more severe in the basal than apical half of the cochlea. Degeneration of the spiral ganglion was most severe when both IHCs and OHCs were absent in the organ of Corti. No survival advantage was identified for type II ganglion cells as has been previously reported. That is, there was no correlation between the degree of degeneration of the spiral ganglion and the prevalence of type II ganglion cells. In fact, there was more severe degeneration of type II cells when the corresponding organ of Corti was severely degenerated. These findings in the human were compared with animal models of degeneration of the spiral ganglion, and the implications for cochlear implantation were discussed. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. FU NIDCD NIH HHS [5 RO1 DC00152-15] NR 41 TC 62 Z9 67 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 1995 VL 90 IS 1-2 BP 192 EP 201 DI 10.1016/0378-5955(95)00165-1 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA TK343 UT WOS:A1995TK34300021 PM 8974997 ER PT J AU LEO, MA ALEYNIK, SI SIEGEL, JH KASMIN, F ALEYNIK, MK LIEBER, CS AF LEO, MA ALEYNIK, SI SIEGEL, JH KASMIN, F ALEYNIK, MK LIEBER, CS TI F-2-ISOPROSTANE EXCRETION IN HUMAN BILE OF PATIENTS WITH BILIARY-TRACT AND PANCREATIC DISORDERS SO HEPATOLOGY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,ALCOHOL RES CTR,LIVER DIS & NUTR SECT,NEW YORK,NY. BETH ISRAEL MED CTR,ALCOHOL RES CTR,LIVER DIS & NUTR SECT,NORTH DIV,NEW YORK,NY. MT SINAI SCH MED,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 12 EP 12 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000011 ER PT J AU YAKICIER, MC FUJIMOTO, J OKAMOTO, E TAKAHASHI, H AF YAKICIER, MC FUJIMOTO, J OKAMOTO, E TAKAHASHI, H TI EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR - GENE IN HEPATOCELLULAR-CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HYOGO MED UNIV,DEPT SURG 1,NISHINOMIYA,HYOGO,JAPAN. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 339 EP 339 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000337 ER PT J AU ITO, T TANAKA, S WANDS, JR AF ITO, T TANAKA, S WANDS, JR TI ROLE OF SIGNAL-TRANSDUCTION PATHWAYS IN HEPATIC TRANSFORMATION-INDUCED BY OVEREXPRESSION OF THE HUMAN INSULIN-RECEPTOR SUBSTRATE-1 (IRS-1) SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 371 EP 371 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000369 ER PT J AU SANTONIRUGIU, E PREISEGGER, KH KISS, A SCHMIDT, EV THORGEIRSSON, SS AF SANTONIRUGIU, E PREISEGGER, KH KISS, A SCHMIDT, EV THORGEIRSSON, SS TI INHIBITION OF NEOPLASTIC DEVELOPMENT IN THE LIVER BY HEPATOCYTE GROWTH-FACTOR IN A TRANSGENIC MOUSE MODEL SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 451 EP 451 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000449 ER PT J AU TOKUSHIGE, K WAKITA, T MORADPOUR, D WANDS, JR AF TOKUSHIGE, K WAKITA, T MORADPOUR, D WANDS, JR TI EXPRESSION AND IMMUNE-RESPONSE TO HEPATITIS-C VIRUS-DNA VACCINE CONSTRUCTS SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 454 EP 454 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000454 ER PT J AU SCAGLIONI, PP MELEGARI, M TAKAHASHI, M CHOWDHURY, R WANDS, JR AF SCAGLIONI, PP MELEGARI, M TAKAHASHI, M CHOWDHURY, R WANDS, JR TI USE OF DOMINANT-NEGATIVE MUTANTS OF THE HEPADNAVIRAL CORE PROTEIN AS ANTIVIRAL AGENTS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,ALBERT EINSTEIN COLL MED,CTR LIVER,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 472 EP 472 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000471 ER PT J AU LIEBER, CS LEO, MA ALEYNIK, SI ALEYNIK, MA DECARLI, LM AF LIEBER, CS LEO, MA ALEYNIK, SI ALEYNIK, MA DECARLI, LM TI POLYENYLPHOSPHATIDYLCHOLINE (PPC) DECREASES OXIDANT STRESS AND PROTECTS AGAINST ALCOHOL-INDUCED LIVER-INJURY IN THE BABOON SO HEPATOLOGY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,ALCOHOL RES CTR,LIVER DIS & NUTR SECT,NEW YORK,NY. MT SINAI SCH MED,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 475 EP 475 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000473 ER PT J AU TANAKA, S ITO, T WANDS, JR AF TANAKA, S ITO, T WANDS, JR TI CELLULAR-TRANSFORMATION INDUCED BY INSULIN-RECEPTOR SUBSTRATE-1 OVEREXPRESSION REQUIRES AN INTERACTION WITH BOTH GRB2 AND SYP SIGNAL-TRANSDUCTION MOLECULES SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR MGH CANC,MOLEC HEPATOL LAB,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 509 EP 509 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000511 ER PT J AU ALEYNIK, SI LEO, MA ALEYNIK, MK LIEBER, CS AF ALEYNIK, SI LEO, MA ALEYNIK, MK LIEBER, CS TI INCREASED CIRCULATING F-2-ISOPROSTANES (F-2-IP) IN PATIENTS WITH SEVERE ALCOHOLIC LIVER-DISEASE SO HEPATOLOGY LA English DT Meeting Abstract C1 BRONX VET ADM MED CTR,ALCOHOL RES CTR,LIVER DIS & NUTR SECT,NEW YORK,NY. MT SINAI SCH MED,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 554 EP 554 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000554 ER PT J AU BAUMERT, TF ROGERS, SA HASEGAWA, K LIANG, TJ AF BAUMERT, TF ROGERS, SA HASEGAWA, K LIANG, TJ TI HBV CORE PROMOTOR MUTATIONS CAUSE ENHANCED VIRAL REPLICATION IN ASSOCIATION WITH FULMINANT-HEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,GI UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 614 EP 614 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000614 ER PT J AU HASEGAWA, K KOJIMA, S ISHIKAWA, K SHIZUMA, T TORII, N KATO, J YAMAUCHI, K HAYASHI, N LIANG, TJ AF HASEGAWA, K KOJIMA, S ISHIKAWA, K SHIZUMA, T TORII, N KATO, J YAMAUCHI, K HAYASHI, N LIANG, TJ TI HYPERIMMUNE RESPONSE IN MICE TO VIRAL-ANTIGENS PRODUCED BY TRANSGENE OF FULL-LENGTH HBV FROM FULMINANT-HEPATITIS PATIENT SO HEPATOLOGY LA English DT Meeting Abstract C1 TOKYO WOMENS MED COLL,INST GASTRO,TOKYO,JAPAN. MASSACHUSETTS GEN HOSP,GI UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 617 EP 617 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000616 ER PT J AU MELEGARI, M SCAGLIONI, PP WANDS, JR AF MELEGARI, M SCAGLIONI, PP WANDS, JR TI CHARACTERIZATION OF A LIVER-SPECIFIC HBX INTERACTING PROTEIN XIP SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 623 EP 623 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000621 ER PT J AU SUN, EC HUANG, JK KWONG, J LIANG, TJ AF SUN, EC HUANG, JK KWONG, J LIANG, TJ TI USE OF THE YEAST 2-HYBRID SYSTEM TO STUDY THE FUNCTION OF HEPATITIS-B VIRUS X PROTEIN SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,GI UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 624 EP 624 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000623 ER PT J AU KOZIEL, MJ HUANG, J LIANG, TJ AF KOZIEL, MJ HUANG, J LIANG, TJ TI TETRACYCLINE-REGULATED EXPRESSION OF HEPATITIS-B VIRUS X PROTEIN - AN INDUCIBLE SYSTEM APPLICABLE TO ANY GENE-PRODUCT SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 625 EP 625 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000624 ER PT J AU NIWAMOTO, H TAKAHASHI, H AF NIWAMOTO, H TAKAHASHI, H TI FAS-MEDIATED INTRACELLULAR INACTIVATION OF HEPATITIS-B VIRUS-DNA SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 629 EP 629 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000628 ER PT J AU LI, JS TONG, SP WANDS, JR AF LI, JS TONG, SP WANDS, JR TI A BINDING-PROTEIN FOR CARBOXYL-TERMINAL DIBASIC AMINO-ACID-RESIDUES OF TRUNCATED DUCK HEPATITIS-B VIRUS PRE-S PROTEIN SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 649 EP 649 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000648 ER PT J AU TONG, SP LI, JS WANDS, JR AF TONG, SP LI, JS WANDS, JR TI INTERACTION BETWEEN A CARBOXYPEPTIDASE-LIKE PROTEIN AND NEUTRALIZING EPITOPES OF DUCK HEPATITIS-B VIRUS PRE-S PROTEIN SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 650 EP 650 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000650 ER PT J AU BUCHER, NLR STIEGLITZJOSEPH, K RADNER, B BOYCE, FM AF BUCHER, NLR STIEGLITZJOSEPH, K RADNER, B BOYCE, FM TI HIGH-EFFICIENCY TRANSFECTION OF CULTURED-HEPATOCYTES BY MODIFIED BACULOVIRAL VECTORS SO HEPATOLOGY LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 787 EP 787 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000784 ER PT J AU ALVARO, D FOLLI, F JEZEQUEL, AM GIGLIOZZI, A KAHN, CR BENEDETTI, A AF ALVARO, D FOLLI, F JEZEQUEL, AM GIGLIOZZI, A KAHN, CR BENEDETTI, A TI INVOLVEMENT OF PHOSPHATIDYLINOSITOL-3-KINASE (PI3-K) IH REGULATION OF ENDOCYTOTIC-TRANSCYTOTIC PATHWAYS AND BILE SECRETION SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV ROME,DEPT GASTRO 2,ROME,ITALY. HOSP SAN RAFFAELE,DEPT MED 1,I-20132 MILAN,ITALY. JOSLIN DIABET CTR,BOSTON,MA 02215. UNIV ANCONA,DEPT GASTRO,ANCONA,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 809 EP 809 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000807 ER PT J AU GEISSLER, M TOKUSHIGE, K WANDS, JR AF GEISSLER, M TOKUSHIGE, K WANDS, JR TI POLYNUCLEOTIDE BASED IMMUNIZATION - STUDY OF THE HUMORAL AND THE CELLULAR IMMUNE-RESPONSE TO HEPATITIS-B VIRUS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 869 EP 869 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000867 ER PT J AU ETO, T TRUBETSKOY, VS TORCHILIN, VP TAKAHASHI, H AF ETO, T TRUBETSKOY, VS TORCHILIN, VP TAKAHASHI, H TI TARGETED TREATMENT OF HEPATITIS-B VIRUS (HBV) INFECTION BY ASIALO-INTERFERON-BETA AND ASSESSMENT OF ITS EFFECT USING HBV NUDE-MICE MODEL ESTABLISHED BY IN-VIVO TRANSFECTION SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 882 EP 882 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000881 ER PT J AU NAOUMOV, NV PERRILLO, RP CHOKSHI, S DIENSTAG, JL VICARY, C BROWN, N WILLIAMS, R AF NAOUMOV, NV PERRILLO, RP CHOKSHI, S DIENSTAG, JL VICARY, C BROWN, N WILLIAMS, R TI REDUCTION IN HEPATITIS-B VIRUS QUASI-SPECIES DURING LAMIVUDINE TREATMENT IS ASSOCIATED WITH ENHANCED VIRUS-REPLICATION AND HEPATOCYTOLYSIS SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV LONDON KINGS COLL HOSP,INST LIVER STUDIES,LONDON,ENGLAND. OCHSNER CLIN & ALTON OCHSNER MED FDN,NEW ORLEANS,LA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GLAXO INC,RES INST,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 885 EP 885 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000883 ER PT J AU DIBISCEGLIE, AM BABBITT, BP CAPLAN, B BHAN, AK RALL, CJN DIENSTAG, JL AF DIBISCEGLIE, AM BABBITT, BP CAPLAN, B BHAN, AK RALL, CJN DIENSTAG, JL TI AUTOLOGOUS LYMPHOCYTE THERAPY (ALT) FOR CHRONIC HEPATITIS-B - A PRELIMINARY-STUDY IN CHIMPANZEES SO HEPATOLOGY LA English DT Meeting Abstract C1 ST LOUIS UNIV,ST LOUIS,MO 63103. CELLCOR INC,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 892 EP 892 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000890 ER PT J AU WAKITA, T MORADPOUR, D TOKUSHIGE, K WANDS, JR AF WAKITA, T MORADPOUR, D TOKUSHIGE, K WANDS, JR TI SPECIFIC-INHIBITION OF HEPATITIS-C VIRUS CORE ANTIGEN PRODUCTION BY ANTISENSE RNA CONSTRUCTS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 893 EP 893 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000891 ER PT J AU MORADPOUR, D WAKITA, T ENGLERT, C WANDS, JR AF MORADPOUR, D WAKITA, T ENGLERT, C WANDS, JR TI SPECIFIC-INHIBITION OF HEPATITIS-C VIRUS GENE-EXPRESSION BY ANTISENSE OLIGONUCLEOTIDES IN A TIGHTLY REGULATED CELL-CULTURE SYSTEM SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,MOLEC GENET LAB,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 894 EP 894 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000893 ER PT J AU WONG, DKH KOZIEL, MJ DUDLEY, D WONG, JT AFDAHL, N RICE, C HOUGHTON, M WALKER, BD AF WONG, DKH KOZIEL, MJ DUDLEY, D WONG, JT AFDAHL, N RICE, C HOUGHTON, M WALKER, BD TI HEPATITIS-C VIRUS-SPECIFIC CYTOTOXIC T-LYMPHOCYTES FROM LIVER AND PERIPHERAL-BLOOD OF A PATIENT WITH A SUSTAINED RESPONSE TO INTERFERON THERAPY SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. BOSTON CITY HOSP,BOSTON,MA 02118. UNIV WASHINGTON,ST LOUIS,MO. CHIRON CORP,EMERYVILLE,CA 94608. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 910 EP 910 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69000909 ER PT J AU IWATA, K WAKITA, T OKUMURA, A YOSHIOKA, K TAKAYANAGI, R WANDS, JR KAKUMU, S AF IWATA, K WAKITA, T OKUMURA, A YOSHIOKA, K TAKAYANAGI, R WANDS, JR KAKUMU, S TI INTERFERON-GAMMA PRODUCTION BY PERIPHERAL-BLOOD LYMPHOCYTES TO HEPATITIS-C VIRUS CORE PROTEIN IN CHRONIC HEPATITIS-C INFECTION SO HEPATOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; NON-B-HEPATITIS; NON-A; MONONUCLEAR-CELLS; RESPONSES; VARIANTS; ANTIGENS; SEQUENCE; PEPTIDES; REGIONS AB Evidence suggests that cellular immunity to hepatitis C virus (HCV) core protein may be important in the pathogenesis of viral infection. Therefore, interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) derived from patients with chronic HCV infection (genotype 1b) was examined. The cellular immune response was evaluated with a recombinant HCV core fusion protein derived from a patient with genotype 1b. To identify the immunodominant epitopes, IFN-gamma production in responders was also assessed with a panel of nine synthetic peptides that covered the entire core region, It was found that mononuclear cells from 24 (52%) of 46 patients with chronic liver disease responded to the core protein; asymptomatic HCV carriers demonstrated a lower response rate (14%, P < .05). More important, individuals who had received IFN-alpha treatment and went into clinical and virological remission had a higher response rate (75%, P < .05) compared with those with ongoing hepatitis whose treatment failed (31%). Of 25 patients whose mononuclear cells responded to HCV core protein, 18 had a significant response to one or more peptides; 12 patients reacted to a peptide mixture containing hydrophilic sequences. The core peptide amino acid sequence 141 to 160 was recognized in 9 patients. Interestingly, 7 of 8 patients bearing HLA DR 4 and w53 haplotypes recognized the peptide sequence 141 to 160. Thus, IFN-gamma production of the mononuclear cell response appeared to be HLA DR restricted, and the responding cells were identified as CD4(+) T cells. This study suggests the presence of immunodominant T cell epitopes within the HCV core protein in association with HLA DR phenotypes in patients with HCV-associated liver disease. C1 NAGOYA UNIV,SCH MED,DEPT INTERNAL MED 3,SHOWA KU,NAGOYA,AICHI 466,JAPAN. MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169, AA-02666] NR 29 TC 53 Z9 53 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 BP 1057 EP 1064 DI 10.1016/0270-9139(95)90609-6 PN 1 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX924 UT WOS:A1995RX92400006 PM 7557851 ER PT J AU GERWECK, KK CHEUNG, AM WONG, DKH AF GERWECK, KK CHEUNG, AM WONG, DKH TI COMPARISON OF BIOCHEMICAL AND VIROLOGICAL RESPONSES TO INTERFERON THERAPY IN CHRONIC HEPATITIS-C - A METAANALYSIS SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 1254 EP 1254 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69001252 ER PT J AU JOHNSON, MW POWELSON, JA AUCHINCLOSS, H DELMONICO, FL COSIMI, AB AF JOHNSON, MW POWELSON, JA AUCHINCLOSS, H DELMONICO, FL COSIMI, AB TI THE EFFECT OF RENAL DYSFUNCTION ON OUTCOME IN HEPATIC TRANSPLANTATION SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 1313 EP 1313 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69001310 ER PT J AU LIANG, TJ AF LIANG, TJ TI P53 PROTEINS AND AFLATOXIN-B1 - THE GOOD, THE BAD, AND THE UGLY SO HEPATOLOGY LA English DT Editorial Material ID HUMAN CANCERS; GENE; MUTATIONS; CARCINOMA; GROWTH; CELLS RP LIANG, TJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 21 TC 4 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 BP 1330 EP 1332 DI 10.1016/0270-9139(95)90647-9 PN 1 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX924 UT WOS:A1995RX92400044 PM 7557889 ER PT J AU MICHAELSON, J AF MICHAELSON, J TI THE DARWINIAN BASIS OF CELLULAR-ORGANIZATION IN THE LIVER SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 1399 EP 1399 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69001395 ER PT J AU MICHAELSON, J AF MICHAELSON, J TI THE GEOMETRY OF THE LIVER LOBULE SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1995 VL 22 IS 4 SU S BP 1400 EP 1400 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX690 UT WOS:A1995RX69001397 ER PT J AU WALKER, GJ HUSSUSSIAN, CJ FLORE, JF GLENDENING, JM HALUSKA, FG DRACOPOLI, NC HAYWARD, NK FOUNTAIN, JW AF WALKER, GJ HUSSUSSIAN, CJ FLORE, JF GLENDENING, JM HALUSKA, FG DRACOPOLI, NC HAYWARD, NK FOUNTAIN, JW TI MUTATIONS OF THE CDKN2/P16(INK4) GENE IN AUSTRALIAN MELANOMA KINDREDS SO HUMAN MOLECULAR GENETICS LA English DT Article ID FAMILIAL MELANOMA; LINKAGE; MLM; LOCUS; NEVUS AB The cyclin dependent kinase inhibitor 2 (CDKN2) gene on chromosome 9p21 is potentially involved in the genesis of many cancers and is currently under intense investigation as a possible melanoma susceptibility locus. We have analyzed 18 Australian melanoma kindreds for mutations within the coding and neighboring splice junction portions of the CDKN2 gene. In seven kindreds (including our six largest), CDKN2 mutations were found to segregate with the putative melanoma chromosome previously assigned by 9p haplotype analysis. These changes included the duplication of a 24 bp repeat, a deleted C residue resulting in the introduction of a premature stop codon, and four single basepair changes causing amino acid substitutions. Mutations segregated to 46 of 51 affected individuals in these seven kindreds, with three apparent sporadic cases in one family and one in each of another two families. Penetrance was variable (55-100%) among the different mutations. These data provide additional strong support that the CDKN2 gene is the chromosome 9p21 familial melanoma locus. C1 QUEENSLAND INST MED RES,BRISBANE,QLD 4029,AUSTRALIA. NIH,NCHGR,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DEPT SURG,ST LOUIS,MO 63110. MASSACHUSETTS GEN HOSP,DEPT ONCOL,BOSTON,MA 02114. SEQUANA THERAPEUT INC,LA JOLLA,CA 92037. RP WALKER, GJ (reprint author), UNIV SO CALIF,INST MED GENET,DEPT BIOCHEM & MOLEC BIOL,2011 ZONAL AVE HMR601,LOS ANGELES,CA 90033, USA. RI hayward, nicholas/C-1367-2015 OI hayward, nicholas/0000-0003-4760-1033 NR 33 TC 132 Z9 133 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 1995 VL 4 IS 10 BP 1845 EP 1852 DI 10.1093/hmg/4.10.1845 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RZ885 UT WOS:A1995RZ88500004 PM 8595405 ER PT J AU KOIKE, G JACOB, HJ KRIEGER, JE SZPIRER, C HOEHE, MR HORIUCHI, M DZAU, VJ AF KOIKE, G JACOB, HJ KRIEGER, JE SZPIRER, C HOEHE, MR HORIUCHI, M DZAU, VJ TI INVESTIGATION OF THE PHENYLETHANOLAMINE N-METHYLTRANSFERASE GENE AS A CANDIDATE GENE FOR HYPERTENSION SO HYPERTENSION LA English DT Article DE PHENETHANOLAMINE N-METHYLTRANSFERASE; RATS, INBRED STRAINS; DNA; CLONING, MOLECULAR ID BLOOD-PRESSURE; BRAIN-STEM; COMPLETE NUCLEOTIDE; ADRENALINE CONTENT; MEDULLA-OBLONGATA; MESSENGER-RNA; RAT-BRAIN; NEURONS; NUCLEI; ENZYME AB Genetic mapping studies have located a gene, Bp1, that accounts for approximately 30% of the genetic variation in the stroke-prone spontaneously hypertensive rat (SHRSP) to a region on chromosome 10 containing the angiotensin-converting enzyme gene. In humans, the gene encoding phenylethanolamine N-methyltransferase (PNMT) was localized near the angiotensin-converting enzyme gene on human chromosome 17. Since most of human chromosome 17 is known to be homologous to rat chromosome 10 and PNMT is known to play a role in blood pressure homeostasis, we reasoned (1) that the rat gene encoding PNMT (Pnmt) may reside on chromosome 10 within the confidence interval containing Bp1 and (2) that Pnmt is a good candidate gene for Bp1. With the use of a somatic cell hybrid panel and genetic mapping techniques, Pnmt mapped within the confidence interval that contains Bp1. To examine further this possibility of Pii mt as a candidate for Bp1, we cloned and characterized Pnmts of the original parental strains, the Wistar-Kyoto rat and SHRSP from the Heidelberg colony. We did not identify any sequence differences between the Wistar-Kyoto rats and SHRSP in the primary structure, in 1077 bp of the 5'-flanking region, or in the 256-bp 3'-end region, making Pnmt an unlikely gene for the generic basis of salt-loaded hypertension. C1 STANFORD UNIV,SCH MED,FALK CARDIOVASC RES CTR,STANFORD,CA 94305. MASSACHUSETTS GEN HOSP EAST,CARDIOVASC RES CTR,BOSTON,MA. FREE UNIV BRUSSELS,DEPT BIOL MOLEC,BRUSSELS,BELGIUM. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. RI Krieger, Jose/C-3117-2011; OI Krieger, Jose/0000-0001-5464-1792 FU NHLBI NIH HHS [HL-35252, HL-35610, HL-46631] NR 43 TC 14 Z9 15 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 1995 VL 26 IS 4 BP 595 EP 601 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RY410 UT WOS:A1995RY41000001 PM 7558218 ER PT J AU CAI, YC CEFAI, D SCHNEIDER, H RAAB, M NABAVI, N RUDD, CE AF CAI, YC CEFAI, D SCHNEIDER, H RAAB, M NABAVI, N RUDD, CE TI SELECTIVE CD28PYMNM MUTATIONS IMPLICATE PHOSPHATIDYLINOSITOL 3-KINASE IN CD86-CD28-MEDIATED COSTIMULATION SO IMMUNITY LA English DT Article ID T-CELL ACTIVATION; LYMPHOCYTES-T; GROWTH-FACTOR; SH3 DOMAIN; CTLA-4; 3-KINASE; CD28; MOLECULES; RECEPTOR; ANTIGEN AB CD28 costimulatory signals are required for lymphokine production and T cell proliferation. CD28 signaling recruits the intracellular proteins PI 3-kinase, ITK, and GRB-2/SOS. PI 3-kinase and GRB-2/SOS bind the CD28 cytoplasmic pYMNM motif via SH2 domains. We generated CD28 pYMNM mutants and found that Y-191 mutation (Y(191)CD28F) disrupted both PI 3-kinase and GRB-2 binding, while M(194) mutation (M(194)CD28C) disrupted only PI 3-kinase binding. Both mutants still bound ITK. We have assessed the ability of these selective mutants to support IL-2 production upon TCR zeta/ CD3 ligation in the presence of CHO-CD86 (B7-2) cells. Both Y(191)CD28F and M(194)CD28C mutants failed to generate IL-2. These data directly implicate PI 3-kinase in CD28-mediated costimulation leading to IL-2 secretion. Wortmannin, an inhibitor of PI 3-kinase, induced cell apoptosis and as such was unsuitable for use in this study. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MED UNIV S CAROLINA,HOLLINGS CANC CTR,DEPT EXPTL ONCOL,CHARLESTON,SC 29425. RP CAI, YC (reprint author), DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 76 TC 109 Z9 110 U1 4 U2 5 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 1995 VL 3 IS 4 BP 417 EP 426 DI 10.1016/1074-7613(95)90171-X PG 10 WC Immunology SC Immunology GA TB608 UT WOS:A1995TB60800003 PM 7584133 ER PT J AU TENNER, AJ ROBINSON, SL EZEKOWITZ, RAB AF TENNER, AJ ROBINSON, SL EZEKOWITZ, RAB TI MANNOSE-BINDING PROTEIN (MBP) ENHANCES MONONUCLEAR PHAGOCYTE FUNCTION VIA A RECEPTOR THAT CONTAINS THE 126,000 M(R) COMPONENT OF THE C1Q RECEPTOR SO IMMUNITY LA English DT Article ID CARBOHYDRATE-RECOGNITION DOMAINS; PULMONARY SURFACTANT APOPROTEIN; PERIPHERAL-BLOOD MONOCYTES; 1ST COMPLEMENT COMPONENT; ACUTE-PHASE REACTANT; COLLAGEN-LIKE REGION; MEDIATED PHAGOCYTOSIS; SUBCOMPONENT CLQ; POLYMORPHONUCLEAR LEUKOCYTES; MOLECULAR CHARACTERIZATION AB Mannose-binding protein (MBP), Clq, the recognition component of the classical complement pathway, and pulmonary surfactant protein A (SP-A) are members of a family of molecules containing a collagen-like sequence contiguous with a noncollagen-like sequence, and usually having the properties of a lectin. Clq and SP-A have been shown to enhance monocyte FcR- and CR1-mediated phagocytosis, suggesting that the common structural features of the collagen-like domains may provide a basis for this immunologically important function. Results presented here demonstrate that MBP also enhanced FcR-mediated phagocytosis by both monocytes and macrophages, and stimulated CR1-mediated phagocytosis in human culture-derived macrophages and in phorbol ester-activated monocytes. Furthermore, a monoclonal antibody that recognizes a 126,000 M(r) cell surface protein and inhibits Clq-enhanced phagocytosis, inhibited the MBP-mediated enhancement of phagocytosis. Thus, the receptors that mediate the enhancement of phagocytosis by MBP and Clq share at least one critical functional component, the 126,000 M(r) ClqRp. C1 AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD 20855. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. RP TENNER, AJ (reprint author), UNIV CALIF IRVINE,DEPT MOLEC BIOL & BIOCHEM,IRVINE,CA 92717, USA. FU NIAID NIH HHS [AI-27168] NR 68 TC 128 Z9 129 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 1995 VL 3 IS 4 BP 485 EP 493 DI 10.1016/1074-7613(95)90177-9 PG 9 WC Immunology SC Immunology GA TB608 UT WOS:A1995TB60800009 PM 7584139 ER PT J AU WILLERFORD, DM CHEN, JZ FERRY, JA DAVIDSON, L MA, A ALT, FW AF WILLERFORD, DM CHEN, JZ FERRY, JA DAVIDSON, L MA, A ALT, FW TI INTERLEUKIN-2 RECEPTOR-ALPHA CHAIN REGULATES THE SIZE AND CONTENT OF THE PERIPHERAL LYMPHOID COMPARTMENT SO IMMUNITY LA English DT Article ID T-CELLS; LYMPHOCYTES-T; IL-2 RECEPTOR; MICE; PATHWAY; GENE; BINDING; DEFICIENT; SUBUNIT; SYSTEM AB Interleukin-2 receptor alpha chain (IL-2R alpha) expression occurs at specific stages of early T and B lymphocyte development and is induced upon activation of mature lymphocytes. Young mice that lack IL-2R alpha have phenotypically normal development of T and B cells. However, as adults, these mice develop massive enlargement of peripheral lymphoid organs associated with polyclonal T and B cell expansion, which, for T cells, is correlated with impaired activation-induced cell death in vivo. Older IL-2R alpha-deficient mice also develop autoimmune disorders, including hemolytic anemia and inflammatory bower disease. Thus, IL-2R alpha is essential for regulation of both the size and content of the peripheral lymphoid compartment, probably by influencing the balance between clonal expansion and cell death following lymphocyte activation. C1 HARVARD UNIV,SCH MED,DEPT GENET,CTR BLOOD RES,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP WILLERFORD, DM (reprint author), CHILDRENS HOSP,HOWARD HUGHES MED INST,DEPT PEDIAT,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI01173, AI20047] NR 52 TC 659 Z9 671 U1 4 U2 10 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 1995 VL 3 IS 4 BP 521 EP 530 DI 10.1016/1074-7613(95)90180-9 PG 10 WC Immunology SC Immunology GA TB608 UT WOS:A1995TB60800012 PM 7584142 ER PT J AU MITCHEN, J BLETZINGER, D RAGO, R WILDING, G AF MITCHEN, J BLETZINGER, D RAGO, R WILDING, G TI USE OF A DNA MICROFLUOROMETRIC ASSAY TO MEASURE PROLIFERATIVE RESPONSE OF MINK LUNG-CELLS TO PURIFIED TGF-BETA AND TO TGF-BETA ACTIVITY FOUND IN PROSTATE CELL-CONDITIONED MEDIUM SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE TGF-BETA; MINK LUNG ASSAY; DNA MICROFLUORESCENT ASSAY; CONDITIONED MEDIUM; GROWTH FACTORS ID GROWTH FACTOR-BETA; EMBRYO FIBROBLASTS; EPITHELIAL-CELLS; CANCER; SEQUENCE; CULTURE; INVITRO; REGION; MTT AB The proliferative response of Mv1Lu cells to purified TGF beta(1), or TGF beta-like activity released by various cells into medium conditioned over a 24-h period was quantitated by adapting a rapid DNA fluorometric assay. Acid activation of the conditioned medium allowed the amount of biologically latent versus active TGF beta to be quantitated. A neutralizing antibody specific for TGF beta(1, 1.2 and 2.0) completely blocked the growth inhibition observed treating Mv1Lu cells with either purified TGF beta(1) or medium containing secreted TGF beta-like activity conditioned by DU145 prostate cells. In contrast to other assays commonly used to measure TGF beta activity, the proliferative response is related directly to DNA content rather than as a reflection of enzymatic activity or incorporation of H-3-thymidine. The necessity for radioactive isotope usage has been eliminated, and the biological response can be quantitated over a period of days. C1 UNIV WISCONSIN,CTR CLIN CANC,DEPT HUMAN ONCOL,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. FU NCI NIH HHS [CA 09614, CA 50590] NR 27 TC 5 Z9 5 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD OCT PY 1995 VL 31 IS 9 BP 692 EP 697 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA TB080 UT WOS:A1995TB08000009 PM 8564080 ER PT J AU PASCUAL, M SCHIFFERLI, JA AF PASCUAL, M SCHIFFERLI, JA TI ANOTHER FUNCTION OF ERYTHROCYTES - TRANSPORT OF CIRCULATING IMMUNE-COMPLEXES SO INFUSIONSTHERAPIE UND TRANSFUSIONSMEDIZIN LA English DT Review DE COMPLEMENT; CR-1; ERYTHROCYTE; IMMUNE COMPLEX ID COMPLEMENT RECEPTOR TYPE-1; SYSTEMIC LUPUS-ERYTHEMATOSUS; POLYMORPHONUCLEAR LEUKOCYTES; CR-1 RECEPTORS; CELL-SURFACE; INVIVO; GLOMERULONEPHRITIS; CLEARANCE; PRIMATES; MEMBRANE AB Objective: To review the main characteristics of the 'immune complex (IC) transport system of erythrocytes', and its possible relevance for transfusion medicine. Data Sources: Literature search, and results of studies performed in the laboratory of Dr J. Schifferli from 1986 to 1995. Selection Criteria: Peer review journals and work relevant to the topic. Results: When antigen/antibody IC form in the presence of complement, C3b binds covalently to the complexes. Such opsonized complexes attach to cells bearing complement receptor 1 (CR1), which is mostly found on erythrocytes in the circulation. This allows IC to be transported through the circulation to the fixed macrophage system of the liver and spleen. In addition, C3b bound to the complexes is catabolized by factor I (with CR1 as a cofactor) so that the complement-activating properties of the complexes are reduced. Conclusions: Complement and erythrocyte CR1 contribute to the safe and effective elimination of IC in humans. This physiologic system prevents IC deposition in the vessel walls. C1 KANTONSSPITAL,DEPT MED,CH-4031 BASEL,SWITZERLAND. RP PASCUAL, M (reprint author), MASSACHUSETTS GEN HOSP,RENAL UNIT,JACKSON 8,BOSTON,MA 02114, USA. NR 39 TC 9 Z9 10 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1019-8466 J9 INFUSIONSTHERAPIE JI Infusionsther. Transfusionsmed. PD OCT PY 1995 VL 22 IS 5 BP 310 EP 315 PG 6 WC Hematology; Immunology SC Hematology; Immunology GA TH745 UT WOS:A1995TH74500008 PM 8924746 ER PT J AU MALYNN, BA DEMENGEOT, J STEWART, V CHARRON, J ALT, FW AF MALYNN, BA DEMENGEOT, J STEWART, V CHARRON, J ALT, FW TI GENERATION OF NORMAL LYMPHOCYTES DERIVED FROM N-MYC-DEFICIENT EMBRYONIC STEM-CELLS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE DIFFERENTIATION; EMBRYONIC STEM CELLS; HELIX-LOOP-HELIX PROTEINS; LYMPHOCYTE DEVELOPMENT; MYC; TRANSCRIPTION ID B-CELL; C-MYC; BONE-MARROW; TRANSGENIC MICE; DIFFERENTIAL EXPRESSION; GENE-EXPRESSION; DOWN-REGULATION; MOUSE; DISRUPTION; LETHALITY AB Myc family proteins are thought to be transcription factors involved in regulation of cell growth and differentiation. N-myc is expressed at the pre-B cell stage of B cell differentiation and is dramatically induced by the pre-B cell growth factor, IL-7. To test the idea that N-myc plays an important role in lymphocyte development, we assayed the effect of a null N-myc mutation on the differentiation of B and T lineage cells. Homozygous, mutant embryonic stem (ES) cells were injected into blastocysts derived from recombination activating gene (RAG-2)-deficient mice. Since RAG-2 mutant mice fail to develop mature lymphocytes, later-stage lymphocytes that are present in chimeric mice are ES cell derived. Surprisingly, nearly normal numbers of mature T and B cells derived from N-myc-deficient ES cells were found in peripheral lymphoid organs of chimeric mice. lymphocytes were judged to be functional based on responses to mitogens and production of serum IgM and multiple IgG isotypes in chimeric animals. We discuss these findings in relation to N-myc function in lymphocyte development and possible redundancy with other myc genes. C1 CTR BLOOD RES,BOSTON,MA 02115. UNIV LAVAL,HOTEL DIEU,CTR RECH CANCEROL,QUEBEC CITY,PQ G1R 2J6,CANADA. RI demengeot, jocelyne/K-8072-2014; OI Demengeot, Jocelyne/0000-0002-4761-614X FU NCI NIH HHS [CA-42335, CA-61009] NR 50 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 1995 VL 7 IS 10 BP 1637 EP 1647 DI 10.1093/intimm/7.10.1637 PG 11 WC Immunology SC Immunology GA TB413 UT WOS:A1995TB41300012 PM 8562509 ER PT J AU GONZALO, JA MARTINEZA, C SPRINGER, TA GUTIERREZRAMOS, JC AF GONZALO, JA MARTINEZA, C SPRINGER, TA GUTIERREZRAMOS, JC TI ICAM-1 IS REQUIRED FOR T-CELL PROLIFERATION BUT NOT FOR ANERGY OR APOPTOSIS INDUCED BY STAPHYLOCOCCUS-AUREUS ENTEROTOXIN-B IN-VIVO SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE ANERGY; APOPTOSIS; ICAM-1; SEB ID CLONAL DELETION; BACTERIAL SUPERANTIGEN; MONOCLONAL-ANTIBODY; STIMULATION; MOLECULES; INVIVO; MICE; LYMPHOCYTES; ACTIVATION; MEMORY AB The response of T lymphocytes to superantigens requires expression of the appropriate TCR V-beta gene products as well as the establishment of cellular interactions mediated by adhesion molecules. To study the role of intercellular adhesion molecule (ICAM)-1 in the response in vivo to superantigens, we have analyzed the effects induced by the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) in mice which have been made genetically deficient in ICAM-1. SEB treatment of wild-type mice causes proliferation, deletion and anergy of the SEB-reactive V(beta)8(+) T cell population. Here we show that cellular interactions mediated by ICAM-1 are not essential for the induction of anergy or for the deletion of CD4(+)V(beta)8(+) or CD8(+)V(beta)8(+) T cells, but are required for the proliferation of these peripheral T lymphocytes. This is the first demonstration in vivo that the absence of the co-stimulatory signals provided by the interaction of ICAM-1 with its specific ligands impairs the proliferation of SEB-reactive T cells. Interestingly, our study showed that SEB-induced proliferation of CD8(+)V(beta)8(+) T cells from lymph nodes (not from spleen) is independent of the interactions mediated by ICAM-1. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. UNIV AUTONOMA MADRID,CSIC,CTR NACL BIOTECNOL,E-28049 MADRID,SPAIN. NR 43 TC 14 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 1995 VL 7 IS 10 BP 1691 EP 1698 PG 8 WC Immunology SC Immunology GA TB413 UT WOS:A1995TB41300018 PM 8562515 ER PT J AU LEBWOHL, M ABEL, E ZANOLLI, M KOO, J DRAKE, L AF LEBWOHL, M ABEL, E ZANOLLI, M KOO, J DRAKE, L TI TOPICAL THERAPY FOR PSORIASIS SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Review ID ANTHRALIN-INDUCED INFLAMMATION; CHRONIC PLAQUE PSORIASIS; DOUBLE-BLIND; CLOBETASOL PROPIONATE; ADJUNCTIVE THERAPY; ORAL METHOXSALEN; CYCLOSPORINE-A; PLASMA-LEVELS; CALCIPOTRIOL; PUVA C1 MT SINAI SCH MED, DEPT DERMATOL, NEW YORK, NY USA. VANDERBILT UNIV, MED CTR, DEPT MED, DIV DERMATOL, NASHVILLE, TN USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. MASSACHUSETTS GEN HOSP, DEPT DERMATOL, BOSTON, MA 02114 USA. NR 67 TC 23 Z9 25 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD OCT PY 1995 VL 34 IS 10 BP 673 EP 684 PG 12 WC Dermatology SC Dermatology GA RY373 UT WOS:A1995RY37300001 PM 8537153 ER PT J AU NIELSEN, GP OLIVA, E YOUNG, RH ROSENBERG, AE DICKERSIN, GR SCULLY, RE AF NIELSEN, GP OLIVA, E YOUNG, RH ROSENBERG, AE DICKERSIN, GR SCULLY, RE TI ALVEOLAR SOFT-PART SARCOMA OF THE FEMALE GENITAL-TRACT - A REPORT OF 9 CASES AND REVIEW OF THE LITERATURE SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ALVEOLAR SOFT-PART SARCOMA; VAGINA; CERVIX; UTERUS; BROAD LIGAMENT ID UTERINE CERVIX; VAGINA; UTERUS AB Nine alveolar soft-part sarcomas of the female genital tract (four previously reported) occurred in patients 14-38 (mean 29) years of age. The most common clinical presentation was abnormal uterine bleeding. Two tumors were located in the vagina, three in the cervix or lower uterine segment, three in the uterine corpus, and one in the broad ligament. The tumors were solid and well circumscribed, ranging in maximum dimension from 1 to 9.8 (average 3.6) cm and had the characteristic histologic features of alveolar soft-part sarcoma. Granules that were diastase resistant and positive by periodic acid-Schiff (PAS) were present in all the tumors, and PAS-positive, diastase-resistant crystals were present in eight of them. Follow-up information ranging from 9 months to 17 years (average 62 months) was available for all the patients. One patient died of metastatic disease 25 months after diagnosis; eight other patients had uneventful follow-up periods ranging from 9 months to 17 years (average 67 months). The differential diagnosis of these tumors is discussed and the literature reviewed. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. NR 30 TC 42 Z9 44 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 1995 VL 14 IS 4 BP 283 EP 292 DI 10.1097/00004347-199510000-00001 PG 10 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA RW961 UT WOS:A1995RW96100001 PM 8598329 ER PT J AU BROMLEY, B PITCHER, BL KLAPHOLZ, H LICHTER, E BENACERRAF, BR AF BROMLEY, B PITCHER, BL KLAPHOLZ, H LICHTER, E BENACERRAF, BR TI SONOGRAPHIC APPEARANCE OF UTERINE SCAR DEHISCENCE SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Note DE SONOGRAPHY; UTERINE SCAR DEHISCENCE; PLACENTA ID CESAREAN-SECTION; DIAGNOSIS; PREGNANCY AB We describe the sonographic appearance of two cases of uterine scar separation in patients with prior cesarean deliveries, In the first case, the anteriorly located placenta appeared to be a placenta previa with accreta and in the second case the placenta was also located directly beneath the uterine scar thus masking a separation until the third stage of labor was complete, These two cases demonstrate an unusual sonographic and clinical presentation of uterine scar separation involving anteriorly located placentas. C1 MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 10 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD OCT PY 1995 VL 51 IS 1 BP 53 EP 56 DI 10.1016/0020-7292(95)80009-2 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA TA311 UT WOS:A1995TA31100008 PM 8582519 ER PT J AU HOLDEN, SA TEICHER, BA AF HOLDEN, SA TEICHER, BA TI COMBINATIONS OF TNP-470 OR SR-4233 WITH ANTITUMOR ALKYLATING-AGENTS IN EMT-6 SPHEROIDS AND MONOLAYERS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE TNP-470; SR-4233; TIRAPAZAMINE; SPHEROIDS; ISOBOLOGRAMS ID ANGIOGENESIS INHIBITOR TNP-470; TUMOR-GROWTH; HUMAN BREAST; CELL-LINES; AGM-1470; RESISTANCE; CARCINOMA; INVITRO; 3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE; METABOLISM AB EMT-6/Parent and EMT-6/CDDP and EMT-6/CTX in vivo alkylating agent resistant cells were grown as spheroids or as monolayers and their response to cis-diamminedichloroplatinum(II) or 4-hydroperoxycyclophosphamide exposure for 1 h alone or in combination with TNP-470 or SR-4233 was determined. When grown as spheroids, each of the three cell lines were less responsive to cis-diamminedichloroplatinum(II) and 4-hydroperoxycyclophosphamide exposure than when the cells were grown and drug-treated in monolayer. The hypoxic cell selective cytotoxic agent SR-4233 was additive in cytotoxicity with the antitumor alkylating agents in both the monolayer and spheroid cultures as determined by isobologram analysis. The antiangiogenic agent TNP-470 was synergistic in cytotoxicity in combination with cis-diammedichloroplatinum in each of the three cell lines when the cells were grown in monolayer and was additive in cytotoxicity with cis-diamminedichloroplatinum(II) when the cells were grown as spheroids. The combination of TNP-470 and 4-hydroperoxycyclophosphamide resulted in additive cytotoxicity toward both monolayer cultures and spheroids. Thus, co-exposure with TNP-470 or SR-4233 increased the cytotoxicity of the antitumor alkylating agents in both the parental and drug resistant cells grown as monolayers or spheroids. C1 DANA FARBER CANC INST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. NR 40 TC 3 Z9 3 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1995 VL 7 IS 4 BP 777 EP 781 PG 5 WC Oncology SC Oncology GA RW001 UT WOS:A1995RW00100012 PM 21552903 ER PT J AU ROSENFELD, PJ HAHN, LB SANDBERG, MA DRYJA, TP BERSON, EL AF ROSENFELD, PJ HAHN, LB SANDBERG, MA DRYJA, TP BERSON, EL TI LOW INCIDENCE OF RETINITIS-PIGMENTOSA AMONG HETEROZYGOUS CARRIERS OF A SPECIFIC RHODOPSIN SPLICE-SITE MUTATION SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ELECTRORETINOGRAPHY; RETINITIS PIGMENTOSA; RHODOPSIN; ROD PHOTORECEPTOR; SPLICE DONOR SITE MUTATION ID GENE; DEGENERATION; DNA AB Purpose. To determine whether a rhodopsin splice donor site mutation at the 5' end of intron 4 is a cause of autosomal dominant retinitis pigmentosa. Methods. Heterozygous carriers of the same rhodopsin splice site mutation in two pedigrees were identified using single-strand conformation polymorphism analysis. Twelve heterozygous carriers were evaluated by ophthalmoscopy, Goldmann kinetic visual fields, dark adaptation thresholds, and full-held electroretinograms including rod intensity-response functions. Clinical findings from the heterozygous carriers of the splice site mutation were compared with those from heterozygous carriers from a separate family with a known recessive rhodopsin null mutation, Glu249X. Results. Analysis of DNA from 48 members of two pedigrees revealed 25 heterozygous carriers of the splice site mutation, ranging in age from 14 to 82 years. There were no homozygotes with the rhodopsin splice site mutation. Of the 25 heterozygous carriers, 24 were asymptomatic, Eleven asymptomatic heterozygotes were examined, including four older than 65 pars of age. They were found to have normal fundi, full visual fields, and slightly elevated final rod dark adaptation thresholds. Their rod electroretinographic b-wave amplitudes were slightly diminished over the full range of blue light intensities. Rod a-wave implicit times were slightly but significantly prolonged in response to the brightest blue flash of light. These subtle abnormalities in rod function were similar to those found in asymptomatic heterozygous carriers of the recessive Glu249X mutation. Only one of the 25 heterozygous carriers of the splice site mutation had symptoms and signs of retinitis pigmentosa. Conclusions. Because 96% of these heterozygous carriers do not have retinitis pigmentosa, it is unlikely that this mutation in intron 4 is a dominant allele. The subtle abnormalities of rod function found in asymptomatic carriers are similar to those found in heterozygous carriers of a recessive rhodopsin allele. The one heterozygous carrier with retinitis pigmentosa probably has a second mutation in the rhodopsin gene or has a defect or defects in another gene that causes his disease. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,TAYLOR SMITH LAB,BOSTON,MA 02114. FU NEI NIH HHS [EY00169, EY08683] NR 16 TC 15 Z9 15 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 1995 VL 36 IS 11 BP 2186 EP 2192 PG 7 WC Ophthalmology SC Ophthalmology GA RY891 UT WOS:A1995RY89100008 PM 7558711 ER PT J AU SCHULZE, E FERRUCCI, JT POSS, K LAPOINTE, L BOGDANOVA, A WEISSLEDER, R AF SCHULZE, E FERRUCCI, JT POSS, K LAPOINTE, L BOGDANOVA, A WEISSLEDER, R TI CELLULAR UPTAKE AND TRAFFICKING OF A PROTOTYPICAL MAGNETIC IRON-OXIDE LABEL IN-VITRO SO INVESTIGATIVE RADIOLOGY LA English DT Article DE RECEPTORS; ENDOCYTOSIS; LYSOSOMES; IRON OXIDE; TARGETING; CONTRAST AGENT; MAGNETIC RESONANCE ID MACROPHAGES; LYSOSOMES; MACROPINOCYTOSIS; MICROTUBULES; CELLS AB RATIONALE AND OBJECTIVES. Target-specific magnetic resonance (MR) contrast agents are being developed to improve the accuracy of MR imaging, The purpose of this study was to determine the mechanism of cell uptake, and modes of intracellular trafficking of a prototypical iron oxide label (RMA) used in the synthesis of some target-specific MR contrast agents. METHODS. The prototypical agent (RMA) consisted of a dextran-coated monocrystalline iron oxide that was modified with rhodamine (fluorescent label) and opsonized with albumin, Fluorescence microscopy was performed in a phagocytic C6 cell line and in murine bone marrow macrophages. Immunohistochemistry against lysosomal markers was used to confirm the intracellular location of the label. RESULTS. RR?IA was identified inside cells after incubation at concentrations as low as 4.0 X 10(-10) M Fe, typically observed with receptor mediated endocytosis and several orders of magnitude lower than that expected with fluid phase pinocytosis. Cell uptake could be inhibited by excess protein but not by dextran, RMA localized initially to tubular and to round intracellular organelles and co-localized with an antibody against a murine lysosomal glycoprotein antibodies (LGP-A) in macrophages, Three days after incubation, RMA was concentrated in perinuclear vesicles, which most likely represent terminal lysosomes where final breakdown appears to occur. CONCLUSIONS. The mechanism of cellular uptake of a prototypical opsonized iron oxide label is consistent with receptor-mediated endocytosis, Immediately after cell contact, RMA localizes to the lysosomal compartment and at long time points reside in vesicles that by morphology and distribution appear to be terminal lysosomes. Iron oxides therefore demonstrate metabolism via the lysosomal pathway. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,MRPP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [1ROI CA 54886-01, 1ROI CA 59649-01] NR 17 TC 105 Z9 109 U1 3 U2 17 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD OCT PY 1995 VL 30 IS 10 BP 604 EP 610 DI 10.1097/00004424-199510000-00006 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TC029 UT WOS:A1995TC02900006 PM 8557500 ER PT J AU CULLEN, DJ BATES, DW SMALL, SD COOPER, JB NEMESKAL, AR LEAPE, LL AF CULLEN, DJ BATES, DW SMALL, SD COOPER, JB NEMESKAL, AR LEAPE, LL TI THE INCIDENT REPORTING SYSTEM DOES NOT DETECT ADVERSE DRUG EVENTS - A PROBLEM FOR QUALITY IMPROVEMENT SO JOINT COMMISSION JOURNAL ON QUALITY IMPROVEMENT LA English DT Article ID SURVEILLANCE; HOSPITALS; PROGRAM AB Objectives: The objectives of this study were 1) to determine the frequency with which adverse drug events result in an incident report (IR) in hospitalized patients; and 2) to determine if there were differences between quality assurance administrators, nurse leaders in quality assurance, and staff nurses as to whether an incident report should or would be filed for each adverse drug event. Study design: All patient admitted to five patient care units (one medical intensive care unit, two surgical intensive care units, and two medical general care units) in one academic tertiary care hospital were studied between February and July 1993. The main outcome measures used were adverse drug events (ADEs) and IRs. Consensus voting was used by senior hospital administrators, nursing leaders, and staff nurses to determine whether an adverse drug event should have been reported and would have been reported. Results: Of 54 adverse drug events identified by the study, only 3 patients (6%) had a corresponding incident report submitted to the hospital's quality assurance program or called into the pharmacy hotline. One additional ADE was identified by an IR, but not by the ADE study. Of the 55 ADEs, 15 were preventable, and 26 were serious or life-threatening, yet only 2 of the 26 led to an incident report. The three voting groups agreed that most ADEs justified an IR, but judged that in actual practice, an IR would infrequently have been filed. Conclusions: Voluntary reporting identified only a small fraction of ADEs. Using IRs for quality assurance/quality improvement will lead to significant bias when assessing quality of care. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV GEN MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP CULLEN, DJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114, USA. FU AHRQ HHS [R01-HS07107-01] NR 23 TC 336 Z9 341 U1 1 U2 9 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1070-3241 J9 JOINT COMM J QUAL IM JI Jt. Comm. J. Qual. Improv. PD OCT PY 1995 VL 21 IS 10 BP 541 EP 548 PG 8 WC Health Policy & Services SC Health Care Sciences & Services GA TA266 UT WOS:A1995TA26600006 PM 8556111 ER PT J AU BIEDERMAN, J MILBERGER, S FARAONE, SV LAPEY, KA REED, ED SEIDMAN, LJ AF BIEDERMAN, J MILBERGER, S FARAONE, SV LAPEY, KA REED, ED SEIDMAN, LJ TI NO CONFIRMATION OF GESCHWINDS HYPOTHESIS OF ASSOCIATIONS BETWEEN READING-DISABILITY, IMMUNE DISORDERS, AND MOTOR PREFERENCE IN ADHD SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; LEFT-HANDEDNESS; LEARNING-DISABILITIES; CEREBRAL-DOMINANCE; CHILDREN; COMORBIDITY; DISEASE; SAMPLE; RISK AB Geschwind and colleagues have proposed an association among reading disability, immune disorder, and motor preference. Although reading disability commonly overlaps with attention deficit hyperactivity disorder (ADHD), ADHD has not been previously examined in studies evaluating Geschwind's hypothesis. In this paper we evaluate whether ADHD is associated with either asthma or left motor preference and whether asthma and left motor preference are associated with each other. Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (n = 140) and normal controls (n = 120). Information on reading disability, asthma, and motor preference was obtained in a standardized manner blind to the proband's clinical status. Neither ADHD nor reading disability was associated with either asthma or left motor preference nor was asthma and left motor preference associated with one another. Our results are not consistent with Geschwind's hypothesis linking reading disability, immune disorder, and left motor preference. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,PSYCHIAT SERV,BROCKTON,MA 02401. MASSACHUSETTS MENTAL HLTH CTR,NEUROPSYCHOL LAB,BOSTON,MA 02115. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,ACC-725,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-01A2] NR 35 TC 13 Z9 13 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD OCT PY 1995 VL 23 IS 5 BP 545 EP 552 DI 10.1007/BF01447660 PG 8 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA TD016 UT WOS:A1995TD01600001 PM 8568078 ER PT J AU RICHARDSON, JH ZANI, C SODROSKI, JG WALDMANN, TA MARASCO, WA AF RICHARDSON, JH ZANI, C SODROSKI, JG WALDMANN, TA MARASCO, WA TI PHENOTYPIC KNOCKOUT OF THE INTERLEUKIN-2 RECEPTOR IN HTLV-I TRANSFORMED-CELL LINES SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. NCI,METAB BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1995 VL 10 IS 2 BP 131 EP 131 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RW330 UT WOS:A1995RW33000148 ER PT J AU KURREK, MM CASTILLO, L BLOCH, KD TANNENBAUM, SR ZAPOL, WM AF KURREK, MM CASTILLO, L BLOCH, KD TANNENBAUM, SR ZAPOL, WM TI INHALED NITRIC-OXIDE DOES NOT ALTER ENDOTOXIN-INDUCED NITRIC-OXIDE SYNTHASE ACTIVITY DURING RAT LUNG PERFUSION SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE REGULATION; EX VIVO RAT LUNG ID MODULATION; CEREBELLUM; NITRATE AB Nitric oxide (NO) has been demonstrated to decrease its own synthesis in tissue preparations. We tested the hypothesis that endogenous NO synthesis induced by lipopolysaccharides (LPS) would be decreased by exogenous NO during isolated lung perfusion. Rats were pretreated with either saline or LPS 48 h before lung harvest. Endogenous NO synthase activity was measured as conversion of L-[C-14]arginine to L-[C-14]citrulline during 90 min of perfusion. NO (100 ppm) was added to the ventilating gas during perfusion of lungs from one group of control or LPS-treated rats. A second group of control or LPS-treated rats was exposed chronically to 100 ppm NO for the 48 h before lung harvest, in addition to receiving 100 ppm NO added to the ventilating gas during lung perfusion. We conclude that conversion of L-[C-14]arginine to L-[C-14]citrulline was minimal in control lungs and increased in response to LPS pretreatment. NO added to the ventilating gas for the 90 min of ex vivo perfusion did not alter the rate of L-[C-14]citrulline production. In vivo exposure to 100 ppm NO for 48 h did not alter the induction of inducible NO synthase activity as measured during ex vivo lung perfusion. This indicates that inhaled NO does not exert negative-feedback inhibition on inducible NO synthase in the ex vivo rat lung. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,GEN MED SERV,BOSTON,MA 02114. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02215. MIT,DEPT CHEM & TOXICOL,CAMBRIDGE,MA 02139. FU NCI NIH HHS [CA-26731]; NHLBI NIH HHS [HL-42397] NR 24 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 1995 VL 79 IS 4 BP 1088 EP 1092 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA TA620 UT WOS:A1995TA62000005 PM 8567547 ER PT J AU GUYTON, GP STANEK, KS SCHNEIDER, RC HOCHACHKA, PW HURFORD, WE ZAPOL, DG LIGGINS, GC ZAPOL, WM AF GUYTON, GP STANEK, KS SCHNEIDER, RC HOCHACHKA, PW HURFORD, WE ZAPOL, DG LIGGINS, GC ZAPOL, WM TI MYOGLOBIN SATURATION IN FREE-DIVING WEDDELL SEALS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE DESATURATION; DIVING MAMMALS; OXYGEN CONSUMPTION; BREATHHOLD DIVING; NEAR-INFRARED SPECTROSCOPY ID CONFLICTING METABOLIC DEMANDS; BLOOD-FLOW; HEMOGLOBIN; EXERCISE; TENSIONS; MUSCLE; HEART AB Although the consumption of myoglobin-bound O-2 (MbO(2)) stores in seal muscles has been demonstrated in seal muscles during laboratory simulations of diving, this may not be a feature of normal field diving in which measurements of heart rate and lactate production show marked differences from the profound diving response induced by forced immersion. To evaluate the consumption of muscle MbO(2) stores during unrestrained diving, we developed a submersible dual-wavelength laser near-infrared spectrophotometer capable of measuring MbO(2) saturation in swimming muscle. The probe was implanted on the surface of the latissimus dorsi of five subadult male Weddell seals (Leptonychotes weddelli) released into a captive breathing hole near Ross Island, Antarctica. Four seals had a monotonic decline of muscle O-2 saturation during free diving to depths up to 300 m with median slopes of -5.12 +/- 4.37 and -2.54 +/- 1.95%/min for dives lasting <17 and >17 min, respectively. There was no correlation between the power consumed by swimming and the desaturation rate. Two seals had occasional partial muscle resaturations late in dives, indicating transfer of Oz from circulating blood to muscle myoglobin. Weddell seals partially consume their MbO(2) stores during unrestrained free diving. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. UNIV BRITISH COLUMBIA,DEPT BIOCHEM,VANCOUVER,BC V6T 2A9,CANADA. NATL WOMENS HOSP,AUCKLAND 3,NEW ZEALAND. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 19 TC 60 Z9 60 U1 2 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 1995 VL 79 IS 4 BP 1148 EP 1155 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA TA620 UT WOS:A1995TA62000014 PM 8567556 ER PT J AU PIERSON, JL HARRIS, WH AF PIERSON, JL HARRIS, WH TI EFFECT OF IMPROVED CEMENTING TECHNIQUES ON THE LONGEVITY OF FIXATION IN REVISION CEMENTED FEMORAL ARTHROPLASTIES - AVERAGE 8.8-YEAR FOLLOW-UP PERIOD SO JOURNAL OF ARTHROPLASTY LA English DT Article DE CEMENT TECHNIQUE; ASEPTIC LOOSENING; REVISION; FEMORAL ARTHROPLASTY AB Forty-six revision cemented femoral arthroplasties in which second-generation cementing techniques were used have been reviewed. After an average follow-up period of 8.8 years, 91% of the femoral components remained in place and 87% remained well fixed. Only 7% were rerevised for aseptic loosening. These results demonstrate a marked improvement over those of first-generation cementing techniques. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 0 TC 19 Z9 22 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 1995 VL 10 IS 5 BP 581 EP 591 PG 11 WC Orthopedics SC Orthopedics GA RY596 UT WOS:A1995RY59600002 PM 9273367 ER PT J AU AUSTIN, KS SILISKI, JM AF AUSTIN, KS SILISKI, JM TI SYMPTOMATIC HETEROTOPIC OSSIFICATION FOLLOWING TOTAL KNEE ARTHROPLASTY SO JOURNAL OF ARTHROPLASTY LA English DT Note DE HETEROTOPIC OSSIFICATION; TOTAL KNEE ARTHROPLASTY AB Heterotopic ossification has been reported to occur in less than 10% of total knee arthroplasties. When this condition has occurred, it has previously been reported either to be asymptomatic or to cause discomfort that resolves with the passage of time. This case report is the first to note persistent pain and snapping due to heterotopic ossification adherent to the distal femoral cortex that required surgical excision to relieve symptoms after total knee arthroplasty. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. NR 0 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 1995 VL 10 IS 5 BP 695 EP 698 PG 4 WC Orthopedics SC Orthopedics GA RY596 UT WOS:A1995RY59600021 PM 9273386 ER PT J AU WEISS, MA KING, CY AF WEISS, MA KING, CY TI IMINO PROTON-EXCHANGE PROVIDES AN H-1-NMR FOOTPRINT OF PROTEIN-DNA INTERACTIONS - GENERAL STRATEGY AND APPLICATION TO THE SRY HMG BOX SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID DOMAIN AB A novel H-1 nuclear magnetic resonance (NMR) strategy for ''footprinting'' specific protein-DNA target sites is demonstrated Relative rates of site-specific imino-proton exchange in the free and bound DNA duplex are determined by use of laminar-shifted shaped pulses in NOESY spectra 2D exchange crosspeaks between imino (omega(2) dimension) and water (omega(1) dimension) resonances in principle provide site-specific probes of protein binding. Chemical exchange is distinguished from nuclear Overhauser enhancements (NOEs) to bound water by use of POESY spectroscopy. This strategy is illustrated in H-1-NMR studies of the SRY high-mobility group (HMG) box, the Y-chromosome-encoded ''master switch'' for testis determination in man. In a specific complex between the protein and a 15-basepair DNA site, imino-proton exchange was observed to be damped selectively within the six basepair subsite 5'-ATTGTT, previously identified by random binding-site selection as an optimal SRY target sequence. The extent of damping correlates with sites of protein-DNA contacts in the minor groove but not with the magnitude of 1H-NMR complexation shifts. SRY binding has recently been shown to introduce significant distortions in DNA structure. The DNA is sharply bent and underwound; the minor groove is widened and major groove compressed. Our results demonstrate that despite such distortions base pairing is stably maintained. Protein binding in the DNA minor groove shields DNA imino protons from exchange with solvent. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. FU NIGMS NIH HHS [GM51558] NR 18 TC 2 Z9 2 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD OCT PY 1995 VL 13 IS 2 BP 261 EP 268 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TB324 UT WOS:A1995TB32400006 PM 8579786 ER PT J AU HUGHES, DE WRIGHT, KR UY, HL SASAKI, A YONEDA, T ROODMAN, GD MUNDY, GR BOYCE, BF AF HUGHES, DE WRIGHT, KR UY, HL SASAKI, A YONEDA, T ROODMAN, GD MUNDY, GR BOYCE, BF TI BISPHOSPHONATES PROMOTE APOPTOSIS IN MURINE OSTEOCLASTS IN-VITRO AND IN-VIVO SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID TRANSFORMING GROWTH FACTOR-BETA-1; BONE-MARROW CELLS; DNA FRAGMENTATION; PAGETS-DISEASE; NUDE-MICE; RESORPTION; DEATH; DIPHOSPHONATES; MACROPHAGES; INVITRO AB Bisphosphonates inhibit bone resorption and are therapeutically effective in diseases of increased bone turnover, such as Pagers disease and hypercalcemia of malignancy. The mechanisms by which they act remain unclear, Proposed mechanisms include inhibition of osteoclast formation from precursors and inhibitory or toxic effects on mature osteoclasts. We have developed a new in vitro model to study osteoclast survival and in this paper present in vitro and in vivo evidence that may explain both the observed reduction in osteoclast numbers and in bone resorption by mature osteoclasts, namely that bisphosphonates induce programmed cell death (apoptosis). Three bisphosphonates (risedronate, pamidronate, and clodronate) caused a 4- to 24-fold increase in the proportion of osteoclasts showing the characteristic morphology of apoptosis in vitro, This observation was confirmed in vivo in normal mice, in mice with increased bone resorption, and in nude mice with osteolytic cancer metastases, with similar-fold increases to those observed in vitro. Of the three compounds, risedronate, the most potent inhibitor of bone resorption in vivo, was the strongest inducer of osteoclast apoptosis in vitro. Osteoclast apoptosis may therefore be a major mechanism whereby bisphosphonates reduce osteoclast numbers and activity, and induction of apoptosis could be a therapeutic goal for new antiosteoclast drugs. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. FU NCI NIH HHS [CA 40035]; NIAMS NIH HHS [AR-39529]; NIDCR NIH HHS [DE 08569] NR 54 TC 678 Z9 709 U1 2 U2 12 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 1995 VL 10 IS 10 BP 1478 EP 1487 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RX780 UT WOS:A1995RX78000007 PM 8686503 ER PT J AU SINGH, BN KOWEY, PR AF SINGH, BN KOWEY, PR TI CHANGING PERSPECTIVES IN CARDIAC-ARRHYTHMIA CONTROL - AGENTS, TECHNIQUES, GOALS, AND OUTCOMES - INTRODUCTION SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Editorial Material RP SINGH, BN (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CARDIOL SECT 691111E,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 1995 VL 6 IS 10 BP 865 EP 867 DI 10.1111/j.1540-8167.1995.tb00362.x PN 2 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TB521 UT WOS:A1995TB52100001 ER PT J AU SINGH, BN AF SINGH, BN TI EXPANDING INDICATIONS FOR THE USE OF CLASS-III AGENTS IN PATIENTS AT HIGH-RISK FOR SUDDEN-DEATH SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE AMIODARONE; SOTALOL; D-SOTALOL; ARRHYTHMIA SUPPRESSION; CLINICAL TRIALS ID COMPLEX VENTRICULAR ARRHYTHMIAS; MYOCARDIAL-INFARCTION; ANTIARRHYTHMIC DRUGS; DILATED CARDIOMYOPATHY; AMIODARONE; MORTALITY; METAANALYSIS; QUINIDINE; THERAPY; TRIAL AB The evidence that antiarrhythmic compounds that act by slowing conduction velocity increase mortality in patients with cardiac disease is now compelling. Emphasis is now shifting to agents that act by lengthening repolarization and have additional antiadrenergic properties. There is preliminary evidence that pure Class III agents devoid of antisympathetic activity may also increase rather than decrease mortality in certain patients. Thus, in recent years, sotalol and amiodarone have emerged as the preferred agents for the control of most ventricular arrhythmias occurring in the setting of significant heart disease. Sotalol has not been widely studied in postinfarct patients; one trial indicated that the drug did reduce total mortality but the difference did not reach statistical significance. A number of studies with amiodarone in the postmyocardial infarction patients have revealed benefit, but these were from nonblinded studies. Two blinded, placebo-controlled studies are currently ongoing. A potential new indication of amiodarone is in patients with arrhythmias in heart failure in whom amiodarone markedly increased left ventricular ejection fraction, with a pronounced suppressant effect on premature ventricular complexes and nonsustained ventricular tachycardia and a trend for a decrease in mortality in patients with nonischemic cardiomyopathy. The most promising indication of amiodarone in low doses is in the maintenance of sinus rhythm in patients with atrial butter and fibrillation. For the present, amiodarone appears to be the-best prototype of a desirable complex antiarrhythmic compound, if its variegated side effect profile can be favorably modified from knowledge of structure-activity relationships. C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90024 USA. RP SINGH, BN (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, DIV CARDIOL, CARDIOL SECT 691111E, WILSHIRE & SAWTELLE BLVD, LOS ANGELES, CA 90073 USA. NR 47 TC 33 Z9 34 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD OCT PY 1995 VL 6 IS 10 BP 887 EP 900 DI 10.1111/j.1540-8167.1995.tb00365.x PN 2 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TB521 UT WOS:A1995TB52100004 PM 8548110 ER PT J AU PURI, KD FINGER, EB GAUDERNACK, G SPRINGER, TA AF PURI, KD FINGER, EB GAUDERNACK, G SPRINGER, TA TI SIALOMUCIN CD34 IS THE MAJOR L-SELECTIN LIGAND IN HUMAN TONSIL HIGH ENDOTHELIAL VENULES SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NODE VASCULAR ADDRESSIN; ADHESION MOLECULE-1; HOMING RECEPTOR; CELL-SURFACE; FUNCTIONAL-CHARACTERIZATION; LYMPHOCYTES; BINDING; ANTIGEN; IDENTIFICATION; NEUTROPHILS AB Peripheral node addressin (PNAd) is a complex mixture of glycoproteins with L-selectin ligand activity that functions in lymphocyte homing. We have investigated the contribution of the sialomucin CD34 relative to other components of PNAd in lymphocyte tethering and rolling in in vitro laminar flow assays. PNAd was isolated with MECA-79 mAb-Sepharose from tonsillar stroma, and the CD34 component (PNAd,CD34(+)) and CD34-negative component (PNAd,CD34(-)) separated on CD34 mAb-Sepharose, Lymphocytes on the PNAd,CD34(-) fraction tether less efficiently, roll faster and are less resistant to shear detachment than on PNAd. The PNAd,CD34(+) fraction constitutes about half the total functional activity, These studies show that CD34 is a major functional component of PNAd. Ligand activity in both the PNAd,CD34(+) and PNAd,CD34(-) fractions is expressed on mucin-like domains, as shown with O-sialoglycoprotease. The CD34 component of PNAd has about four times higher tethering efficiency than total tonsillar CD34. CD34 from spleen shows no lymphocyte tethering. Although less efficient than the PNAd,CD34(+) fraction from tonsil, CD34 from the KG1a hematopoietic cell line is functionally active as an L-selectin ligand despite lack of reactivity with MECA-79 mAb, which binds to a sulfation-dependent epitope. All four forms of CD34 are active in binding to E-selectin, KG1a CD34 but not spleen CD34 are active as L-selectin ligands, yet both lack MECA-79 reactivity and possess E-selectin ligand activity. This suggests that L-selectin ligands and E-select in ligands differ in more respects than presence of the MECA-79 epitope. C1 NORWEGIAN RADIUM HOSP,INST CANC RES,DEPT IMMUNOL,N-0310 OSLO,NORWAY. HARVARD UNIV,SCH MED,DEPT PATHOL,CTR BLOOD RES,BOSTON,MA 02115. FU NCI NIH HHS [CA 31799] NR 52 TC 125 Z9 126 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT PY 1995 VL 131 IS 1 BP 261 EP 270 DI 10.1083/jcb.131.1.261 PG 10 WC Cell Biology SC Cell Biology GA RX837 UT WOS:A1995RX83700023 PM 7559783 ER PT J AU DALLAS, SL MIYAZONO, K SKERRY, TM MUNDY, GR BONEWALD, LF AF DALLAS, SL MIYAZONO, K SKERRY, TM MUNDY, GR BONEWALD, LF TI DUAL ROLE FOR THE LATENT TRANSFORMING GROWTH-FACTOR-BETA BINDING-PROTEIN IN STORAGE OF LATENT TGF-BETA IN THE EXTRACELLULAR-MATRIX AND AS A STRUCTURAL MATRIX PROTEIN SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; PLASMINOGEN-ACTIVATOR INHIBITOR; CONNECTIVE-TISSUE MICROFIBRILS; MOLECULAR-WEIGHT COMPLEX; MARFAN-SYNDROME; MESSENGER-RNA; HUMAN-PLATELETS; EXPRESSION; FACTOR-BETA-1; FIBRILLIN AB The role of the latent TGF-beta binding protein (LTBP) is unclear. In cultures of fetal rat calvarial cells, which form mineralized bonelike nodules, both LTBP and the TGF-beta 1 precursor localized to large fibrillar structures in the extracellular matrix. The appearance of these fibrillar structures preceded the appearance of type I collagen fibers. Plasmin treatment abolished the fibrillar staining pattern for LTBP and released a complex containing both LTBP and TGF-beta. Antibodies and antisense oligonucleotides against LTBP inhibited the formation of mineralized bonelike nodules in long-term fetal rat calvarial cultures. Immunohistochemistry of fetal and adult rat bone confirmed a fibrillar staining pattern for LTBP in vivo. These findings, together with the known homology of LTBP to the fibrillin family of proteins, suggest a novel function for LTBP, in addition to its role in matrix storage of latent TGF-beta, as a structural matrix protein that may play a role in bone formation. C1 LUDWIG INST CANC RES,S-75124 UPPSALA,SWEDEN. UNIV BRISTOL,DEPT ANAT,BRISTOL BS2 8EJ,AVON,ENGLAND. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. DEPT VET AFFAIRS,AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP DALLAS, SL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ENDOCRINOL & METAB,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 56 TC 194 Z9 200 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT PY 1995 VL 131 IS 2 BP 539 EP 549 DI 10.1083/jcb.131.2.539 PG 11 WC Cell Biology SC Cell Biology GA RZ595 UT WOS:A1995RZ59500020 PM 7593177 ER PT J AU LAMBERTMESSERLIAN, GM CROWLEY, WF SCHNEYER, AL AF LAMBERTMESSERLIAN, GM CROWLEY, WF SCHNEYER, AL TI EXTRAGONADAL ALPHA-INHIBIN PRECURSOR PROTEINS CIRCULATE IN HUMAN MALE SERUM SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; RAT SERTOLI CELLS; HYPOGONADOTROPIC HYPOGONADISM; BINDING-PROTEINS; NORMAL MEN; SUBUNIT; ACTIVIN; RADIOIMMUNOASSAY; FLUID; BOVINE AB The role of inhibin as a negative feedback regulator of pituitary FSH secretion in men remains controversial inasmuch as serum inhibin and FSH levels are often not correlated, in part because of the known alpha-inhibin subunit cross-reactivity of the most widely used inhibin antiserum (Monash #1989). The objective of this study was to identify the nature of these alpha-inhibin proteins in male serum using antisera specific for the alpha-inhibin precursor. Three polyclonal antisera were raised against synthetic peptide fragments from the proregion (amino acids 21-35 = precursor alpha inhibin (PIN) 1 and 42-56 = PIN 2) and alpha-N segment (113-127 = PIN 3) of the human alpha-inhibin precursor protein. These antisera were then used in individual RIAs with the homologous peptide as both standard and radioligand. Because pure human alpha-inhibin subunit proteins are not available, recombinant alpha-inhibin medium and porcine follicular fluid were used as reference preparations in the PIN assays. All assays were specific for alpha-inhibin proteins, i.e. 1) they showed no significant cross-reactivity with other alpha-inhibin peptide fragments, dimeric 32-kDa inhibin, recombinant activin; FSH, human albumin, or the inhibin binding proteins alpha-2 macroglobulin and follistatin, and 2) they recognized native protein in alpha-inhibin precursor-containing porcine follicular fluid and in medium from a recombinant alpha-inhibin-only secreting cell line. Furthermore, immunoreactivity of all serum proteins seen by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting with the PIN antisera was abolished or significantly reduced (40-100%) by preincubation of each PIN antiserum with the homologous peptide. Serial dilutions of serum from normal, GnRH-deficient, and castrate males exhibited equivalent displacement curves in each precursor (PIN) assay, and there were no significant group differences in PIN 2 immunoreactivity between normal (n = 14), GnRH-deficient (n = 8), and castrate men (n = 3). Western blotting of serum samples from a normal and a GnRH-deficient male revealed immunoreactive proteins of approximately 57 and 29 kDa under reducing conditions with all three PIN antisera. An additional 40-kDa protein was observed with the pro-alpha-inhibin antisera, PIN 1 and 2, and a protein of more than 97 kDa was seen with the PIN 2 antiserum. In summary, the present study 1) confirms the presence of circulating alpha-inhibin precursor proteins in male serum independent of testicular function, 2) demonstrates an extragonadal origin of these serum proteins, and 3) identifies multiple forms of these proteins in male serum containing three a-inhibin precursor epitopes. The origin of these circulating ol-inhibin proteins and their physiological role in men are currently under investigation. C1 MASSACHUSETTS GEN HOSP, DEPT MED, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. RP LAMBERTMESSERLIAN, GM (reprint author), MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, REPROD ENDOCRINE UNIT BHX5, BOSTON, MA 02114 USA. FU NICHD NIH HHS [P30-HD28138, T32-HD07396, U54-HD29164] NR 39 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1995 VL 80 IS 10 BP 3043 EP 3049 DI 10.1210/jc.80.10.3043 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RZ377 UT WOS:A1995RZ37700035 PM 7559894 ER PT J AU NISHIO, Y WARREN, CE BUCZEKTHOMAS, JA RULFS, J KOYA, D AIELLO, LP FEENER, EP MILLER, TB DENNIS, JW KING, GL AF NISHIO, Y WARREN, CE BUCZEKTHOMAS, JA RULFS, J KOYA, D AIELLO, LP FEENER, EP MILLER, TB DENNIS, JW KING, GL TI IDENTIFICATION AND CHARACTERIZATION OF A GENE REGULATING ENZYMATIC GLYCOSYLATION WHICH IS INDUCED BY DIABETES AND HYPERGLYCEMIA SPECIFICALLY IN RAT CARDIAC TISSUE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GLYCOSYLATION; CARDIOMYOPATHY; CARDIOMYOCYTES; DIABETIC COMPLICATIONS; GENE REGULATION ID MESSENGER-RNA; DIFFERENTIAL DISPLAY; GLYCEMIC CONTROL; HIGH GLUCOSE; INSULIN; HEART; MUSCLE; CELLS; CARDIOMYOPATHY; EXPRESSION AB Primary cardiac abnormalities have been frequently reported in patients with diabetes probably due to metabolic consequences of the disease, Approximately 2,000 mRNA species from the heart of streptozotocin-induced diabetic and control rats were compared by the mRNA differential display method, two of eight candidate clones thus isolated (DH1 and 13) were confirmed by Northern blot analysis, The expression of clone 13 was increased in the heart by 3.5-fold (P < 0.05) and decreased in the aorta by twofold (P < 0.05) in diabetes as compared to control, Sequence analysis showed that clone 13 is a rat mitochondrial gene, DH1 was predominantly expressed in the heart with an expression level 6.8-fold higher in the diabetic rats than in control (P < 0.001), Insulin treatment significantly (P < 0.001) normalized the expression of DH1 in the hearts of diabetic rats, DH1 expression was observed in cultured rat cardiomyocytes, but not in aortic smooth muscle cells or in cardiac derived fibroblasts, The expression in cardiomyocytes was regulated by insulin and glucose concentration of culture media, The full length cDNA of DH1 had a single open-reading frame with 85 and 92% amino acid identity to human and mouse UDP-GlcNAc:Gal beta 1-3GalNAc alpha R beta 1-6 N-acetylglucosaminyltransferase (core 2 GlcNAc-T), respectively, a key enzyme determining the structure of O-linked glycosylation, Transient transfection of DH1 cDNA into Cos7 cells conferred core 2 GlcNAc-T enzyme activity, In vivo, core 2 GlcNAc-T activity was increased by 82% (P < 0.05) in diabetic hearts vs controls, while the enzymes GlcNAc-TI and GlcNAc-TV responsible for N-linked glycosylation were unchanged, These results suggest that core 2 GlcNAc-T is specifically induced in the heart by diabetes or hyperglycemia. The induction of this enzyme may be responsible for the increase in the deposition of glycoconjugates and the abnormal functions found in the hearts of diabetic rats. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02215. MT SINAI HOSP,SAMUEL LUNENFELD RES INST,TORONTO,ON M5G 1X5,CANADA. UNIV MASSACHUSETTS,SCH MED,DEPT BIOCHEM & MOLEC BIOL,WORCESTER,MA 01655. RI Dennis, James/E-7268-2013 FU NEI NIH HHS [EY05110]; NIDDK NIH HHS [DK36433, DK36836, P30 DK036836] NR 52 TC 53 Z9 53 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1995 VL 96 IS 4 BP 1759 EP 1767 DI 10.1172/JCI118221 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RY954 UT WOS:A1995RY95400010 PM 7560067 ER PT J AU TO, WK FOTHERGILL, AW RINALDI, MG AF TO, WK FOTHERGILL, AW RINALDI, MG TI COMPARATIVE-EVALUATION OF MACRODILUTION AND ALAMAR COLORIMETRIC MICRODILUTION BROTH METHODS FOR ANTIFUNGAL SUSCEPTIBILITY TESTING OF YEAST ISOLATES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FLUCONAZOLE; RESISTANCE AB A comparative evaluation of the macrodilution method and the Alamar colorimetric method for the susceptibility testing of amphotericin B, fluconazole, and flucytosine was conducted with 134 pathogenic yeasts, The clinical isolates included 28 Candida albicans, 17 Candida tropicalis, 15 Candida parapsilosis, 12 Candida krusei, 10 Candida lusitaniae, 9 Candida guilliermondii, 18 Torulopsis glabrata, and 25 Cryptococcus neoformans isolates. The macrodilution method was performed and interpreted according to the recommendations of the National Committee for Clinical Laboratory Standards (document M27-P), and the Alamar colorimetric method was performed according to the manufacturer's instructions. For the Alamar colorimetric method, MICs mere determined at 24 and 48 h of incubation for Candida species and T. glabrata and at 48 and 72 h of incubation for C. neoformans. The overall agreement within +/- 1 dilution for Candida species and T. glabrata against the three antifungal agents was generally good, with the values for amphotericin B, fluconazole, and flucytosine being 85.3, 77.9, and 86.2%, respectively, at the 24-h readings and 69.3, 65.2, and 97.2%, respectively, at the 48-h readings, Most disagreement was noted with fluconazole against C. tropicalis and T. glabrata. Our studies indicate that determination of MICs at 24 h by the Alamar colorimetric method is a valid alternate method for testing amphotericin B, fluconazole, and flucytosine against Candida species but not for testing fluconazole against C. tropicalis and T. glabrata. For flucytosine, much better agreement can be demonstrated against Candida species and T. glabrata at the 48-h readings by the Alamar method, Excellent agreement within +/- 1 dilution can also be observed for amphotericin B, fluconazole, and flucytosine (80, 96, and 96%, respectively) against C, neoformans when the MICs were determined at 72 h by the Alamar method. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,FUNGUS TESTING LAB,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP TO, WK (reprint author), PRINCESS MARGARET HOSP,DEPT PATHOL,2-10 PRINCESS MARGARET HOSP RD,KOWLOON,HONG KONG. NR 26 TC 49 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1995 VL 33 IS 10 BP 2660 EP 2664 PG 5 WC Microbiology SC Microbiology GA RV565 UT WOS:A1995RV56500025 PM 8567901 ER PT J AU FLYNN, CE RUOFF, KL AF FLYNN, CE RUOFF, KL TI IDENTIFICATION OF STREPTOCOCCUS-MILLERI GROUP ISOLATES TO THE SPECIES LEVEL WITH A COMMERCIALLY AVAILABLE RAPID TEST SYSTEM SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID DIFFERENTIATION; CONSTELLATUS; INTERMEDIUS; ANGINOSUS AB Clinical isolates of the ''Streptococcus milleri'' species group were examined by conventional methods and a rapid, commercially available method for the identification of these strains to the species level. The levels of agreement between the identifications obtained with the commercially available system (Fluo-Card Milleri; KEY Scientific, Round Rock, Tex.) and conventional methods were 98% for 50 Streptococcus anginosus strains, 97% for 31 Streptococcus constellatus strains, and 88% for 17 isolates identified as Streptococcus intermedius, Patient records were also studied in order to gain information on the frequency and sites of isolation of each of the three ''S, milleri'' group species. C1 MASSACHUSETTS GEN HOSP,MICROBIOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,JAMES HOLMER WRIGHT PATHOL LABS,BOSTON,MA 02114. NR 17 TC 26 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1995 VL 33 IS 10 BP 2704 EP 2706 PG 3 WC Microbiology SC Microbiology GA RV565 UT WOS:A1995RV56500033 PM 8567909 ER PT J AU WABER, DP TARBELL, NJ FAIRCLOUGH, D ATMORE, K CASTRO, R ISQUITH, P LUSSIER, F ROMERO, I CARPENTER, PJ SCHILLER, M SALLAN, SE AF WABER, DP TARBELL, NJ FAIRCLOUGH, D ATMORE, K CASTRO, R ISQUITH, P LUSSIER, F ROMERO, I CARPENTER, PJ SCHILLER, M SALLAN, SE TI COGNITIVE SEQUELAE OF TREATMENT IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA - CRANIAL RADIATION REQUIRES AN ACCOMPLICE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OSTERRIETH COMPLEX FIGURE; METHOTREXATE; IRRADIATION; PRODUCTIONS; PREVENTION; SEX AB Purpose: We evaluated cognitive sequelae of treatment for childhood acute lymphoblastic leukemia (ALL), CNS therapy consisted of cranial irradiation (CRT) or no radiation. Children were also randomized to single intravenous high-dose methotrexate (HD-MTX) or conventional-dose methotrexate (CD-MTX) during induction, and all patients received intrathecal (IT) and systemic continuation chemotherapy, Patients and Methods: Sixty-six patients treated for ALL on Dana-Farber Cancer Institute protocol 87-01 were evaluated by standardized cognitive and achievement tests, These children had been assigned at diagnosis to a standard-risk (SR) or high-risk (HR) group and received no CRT or 18 Gy CRT, respectively. All patients were randomized to receive MTX during remission induction, either as CD-MTX (40 mg/m(2)) or HD-MTX (4 g/m(2)) with leucovorin rescue, Results: There was no difference in cognitive outcomes between radiated and unirradiated patients (P > .4), However, the HD-MTX/CRT combination was associated with decreased intelligence quotient (IQ estimate, 9.3 points) for girls only (P < .08). A specific deficit in verbal coding and memory was documented for all patients (P < .0001), Conclusion: We conclude the following: (1) 18 Gy CRT per se was not an independent toxic agent for cognitive outcome; (2) HD-MTX during induction was associated with IQ decline in girls, but only when it was followed by CRT; and (3) impairment of verbal memory and coding was a consistent finding that was independent of CRT, which implicates some component of chemotherapy, possibly prednisone, as a CNS toxin. (C) 1995 by American Society of Clinical Oncology. C1 CHILDRENS HOSP,DIV PSYCHOL,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT PEDIAT,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,CAMBRIDGE,MA 02138. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HOP ST JUSTINE,DEPT NEUROPSYCHOL,MONTREAL,PQ H3T 1C5,CANADA. INTER AMER UNIV,DEPT PSYCHOL,HATO REY,PR. UNIV ROCHESTER,MED CTR,DEPT PEDIAT,ROCHESTER,NY 14642. MT SINAI MED CTR,DIV PEDIAT HEMATOL ONCOL,NEW YORK,NY 10029. FU NCI NIH HHS [CA19789]; NICHD NIH HHS [P30-HD18655]; NINDS NIH HHS [NS22108] NR 22 TC 107 Z9 109 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1995 VL 13 IS 10 BP 2490 EP 2496 PG 7 WC Oncology SC Oncology GA RZ744 UT WOS:A1995RZ74400004 PM 7595698 ER PT J AU HAYES, DF VANZYL, JA HACKING, A GOEDHALS, L BEZWODA, WR MAILLIARD, JA JONES, SE VOGEL, CL BERRIS, RF SHEMANO, I SCHOENFELDER, J AF HAYES, DF VANZYL, JA HACKING, A GOEDHALS, L BEZWODA, WR MAILLIARD, JA JONES, SE VOGEL, CL BERRIS, RF SHEMANO, I SCHOENFELDER, J TI RANDOMIZED COMPARISON OF TAMOXIFEN AND 2 SEPARATE DOSES OF TOREMIFENE IN POSTMENOPAUSAL PATIENTS WITH METASTATIC BREAST-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRIPHENYLETHYLENE COMPOUND; PHASE-II; WOMEN; TRIAL; RAT; FC-1157A; THERAPY; DENSITY; LIVER AB Purpose: To perform a randomized three-arm comparison tamoxifen (TAM; 20 mg/d) and two separate doses of toremifene (TOR; 60 mg/d [TOR60] and 200 mg/d [TOR200]) in postmenopausal patients with hormone receptor-positive or -unknown metastatic breast cancer. Materials and Methods: Six hundred forty-eight patients with hormone receptor-positive or -unknown metastatic breast cancer were randomly assigned to receive TAM (n = 215), TOR60 (n = 221), or TOR200 (n = 212). Results: The combined response rates (by intent to treat) were as follows: TAM, 44%; TOR60, 50%; and TOR200, 48%. Complete and partial response rates were as follows: TAM, 19%; TOR60, 21%, and TOR200, 23% (not statistically different). Median times to progression and overall survival were not significantly different. Adverse events (lethal, serious but nonlethal, and important but non-life-threatening) were similar in all three arms, except that patients in the TOR200 arm had a statistically significantly increased rate of nausea (37% v 26% and 26% for TOR200, TAM, and TOR60, respectively; P = .027). Quality-of-life assessments were not different among the three arms. Conclusion: The activity, toxicity, and side effects of TOR in postmenopausal women with hormone receptor-positive or -unknown metastatic breast cancer are similar if not equivalent to those of TAM. We detected no clear evidence of ct dose-response effect for TOR. TOR60 is on effective and safe agent for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer and can be considered an alternative to TAM as first-line treatment for such patients. (C) 1995 by American Society of Clinical Oncology C1 MAMMA CLIN,CAPE TOWN,SOUTH AFRICA. GROOTE SCHUUR HOSP,CAPE TOWN 7925,SOUTH AFRICA. NATL HOSP,BLOEMFONTEIN,SOUTH AFRICA. UNIV WITWATERSRAND,JOHANNESBURG,SOUTH AFRICA. CREIGHTON CANC CTR,OMAHA,NE. BAYLOR UNIV,MED CTR,SAMMONS CANC CTR,DALLAS,TX. MT SINAI COMPREHENS BREAST CTR,COMPREHENS CANC RES GRP INC,MIAMI,FL. COLORADO CANC RES PROGRAM,DENVER,CO. PHARMACIA INC,COLUMBUS,OH. RP HAYES, DF (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 51 TC 179 Z9 181 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1995 VL 13 IS 10 BP 2556 EP 2566 PG 11 WC Oncology SC Oncology GA RZ744 UT WOS:A1995RZ74400013 PM 7595707 ER PT J AU AISENBERG, AC AF AISENBERG, AC TI COHERENT VIEW OF NON-HODGKINS-LYMPHOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID EPSTEIN-BARR-VIRUS; LARGE-CELL LYMPHOMA; BONE-MARROW TRANSPLANTATION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CHRONIC LYMPHOCYTIC-LEUKEMIA; COMBINED MODALITY THERAPY; POLYMERASE CHAIN-REACTION; NERVOUS-SYSTEM LYMPHOMA; STANDARD REGIMEN CHOP; LOW-GRADE LYMPHOMA AB Purpose: Even though non-Hodgkin's lymphoma is already sixth in incidence and mortality among malignant neoplasms (and the incidence was increasing at a rate of 3% to 4% per year before the advent of AIDS epidemic-associated lymphomas), most physicians and many oncolgists find the disorder arcane. The problem lies in the complexity of human lymphoma, which encompasses more than a dozen neoplasms of the lymphoid system, The goal of this review is to provide user-friendly access to the condition, Methods: The variety of inputs required for a subdivision of non-Hodgkin's lymphoma that is useful to clinicians includes lymphocyte lineage and sublineage based on microscopic appearance and immunophenotype, clinical behavior manifest in survival and early dissemination, and analysis of molecular generic and cytogenetic abnormalities, which reflect pathogenic oncogene derangements, Epstein-Barr virus (EBV) and human T-cell leukemia virus type 1 (HTLV-I) ore important in certain uncommon lymphomas, Results and Conclusion: The subtypes of primary B-lineage nodal lymphoma include low-grade (small lymphocytic, lymphoplasmacytic-lymphoplasmacytoid, follicular small cleaved cell, and follicular mixed small cleaved and large cell), intermediate-grade (follicular large cell, diffuse small cleaved or mixed, and intermediate lymphocytic), and high-grade (diffuse large cell, immunoblastic, and small noncleaved cell) neoplasms. The less common lymphomas of T lineage and lymphomas that arise in extranodal sites are placed in separate subdivisions, This subdivision serves as a guide to prognosis and treatment. (C) 1995 by American Society of Clinical Oncology. RP AISENBERG, AC (reprint author), MASSACHUSETTS GEN HOSP,HEMATOL ONCOL UNIT,FRUIT ST,BOSTON,MA 02114, USA. NR 196 TC 91 Z9 94 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1995 VL 13 IS 10 BP 2656 EP 2675 PG 20 WC Oncology SC Oncology GA RZ744 UT WOS:A1995RZ74400026 PM 7595720 ER PT J AU NIEDERMAN, R NALEWAY, C LU, BY BUYLEBODIN, Y ROBINSON, P AF NIEDERMAN, R NALEWAY, C LU, BY BUYLEBODIN, Y ROBINSON, P TI SUBGINGIVAL TEMPERATURE AS A GINGIVAL INFLAMMATORY INDICATOR SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE SUBGINGIVAL TEMPERATURE; GINGIVAL INFLAMMATION; PERIODONTAL DISEASE; BLEEDING ON PROBING; POCKET DEPTH ID HEALTH AB Elevated temperature is one of 4 cardinal inflammatory signs. Previous work indicates that subgingival temperature assessments are accurate and reliable, and provide objective, quantitative information over a broad 10 degrees C range, in small 0.1 degrees C increments with a diner, immediate report on the inflammatory status at the pocket base. However, complicating the use and interpretation of subgingival temperature assessments are its 3 forms: actual subgingival temperature, sublingual temperature minus subgingival temperature (temperature differential), and a temperature indicator light. We reasoned that if one could determine which of the temperature assessments reflected the periodontal condition, and which were independent variables, they would provide new and unique information about the inflammatory status of the periodontium. We also reasoned that by providing objective, quantitative data over a broad range, subgingival temperature should reduce the sample size required to obtain significance in clinical trials. Therefore, the purpose of this study was 2-fold: (1) to determine whether the 3 subgingival temperature assessments could differentiate between clinically defined periodontal health and disease; (2) to determine whether the 3 assessments were dependent or independent clinical variables. The data indicated that all 3 subgingival temperature assessment methods differentiated between clinically-defined periodontal health and disease (all p<0.02). All 3 assessments also correlated significantly (all p<0.03), but modestly (all r>0.49), with bleeding on probing. Based on scatter-plot matrices and common factor analysis, the data indicated that only actual subgingival temperature and temperature differential were independent variables. Taken together, this data indicates that subgingival temperature and temperature differential provide unique information about the periodontal inflammatory state. Power calculations indicated that the temperature differential may significantly reduce the subject number required to achieve significance in clinical trials examining gingival inflammation Because of the body's rapid temperature response, these assessments may also significantly reduce the time required for gingival inflammation trials. C1 AMER DENT ASSOC HLTH FDN,CHICAGO,IL. NORTHWESTERN UNIV,DEPT STOMATOL,CHICAGO,IL 60611. RP NIEDERMAN, R (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-02847, DE-08415, DE-04881] NR 12 TC 13 Z9 15 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 OCT PY 1995 VL 22 IS 10 BP 804 EP 809 DI 10.1111/j.1600-051X.1995.tb00264.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RX429 UT WOS:A1995RX42900011 PM 8682928 ER PT J AU MAAS, JW MILLER, AL TEKELL, JL FUNDERBURG, L SILVA, JA TRUE, J VELLIGAN, D BERMAN, N BOWDEN, CL AF MAAS, JW MILLER, AL TEKELL, JL FUNDERBURG, L SILVA, JA TRUE, J VELLIGAN, D BERMAN, N BOWDEN, CL TI CLONIDINE PLUS HALOPERIDOL IN THE TREATMENT OF SCHIZOPHRENIA PSYCHOSIS SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Note ID NOREPINEPHRINE; NORADRENALINE; DOPAMINE; PLASMA; DRUGS; CSF AB Because of the evidence for increased norepinephrine (NE) production in psychotic patients, we studied the effects of combining the az-adrenergic agonist clonidine with haloperidol for the treatment of schizophrenic psychosis. Twelve hospitalized schizophrenic patients were taken off their antipsychotic medication for 2 to 4 weeks before double-blind treatment with haloperidol (20 mg/day) combined with either clonidine or placebo. The group receiving clonidine was significantly more improved on the thought disorder subscale of the Brief Psychiatric Rating Scale (p = 0.02). The groups differed initially in the level of negative symptoms, but controlling for this difference statistically by analysis of covariance did not change the finding with regard to the superiority of combining clonidine with haloperidol. We conclude that larger treatment trials of combining haloperidol with clonidine are warranted. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. SAN ANTONIO STATE HOSP,CLIN RES UNIT,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. UNIV CALIF LOS ANGELES,HARBOR MED CTR,INST EDUC RES,TORRANCE,CA 90509. NR 22 TC 12 Z9 13 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 1995 VL 15 IS 5 BP 361 EP 364 DI 10.1097/00004714-199510000-00009 PG 4 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA RY196 UT WOS:A1995RY19600010 PM 8830068 ER PT J AU PEDROZO, HA SCHWARTZ, Z NAKAYA, H HARRISON, JL DEAN, DD WIEDERHOLD, ML BOYAN, BD AF PEDROZO, HA SCHWARTZ, Z NAKAYA, H HARRISON, JL DEAN, DD WIEDERHOLD, ML BOYAN, BD TI CARBONIC-ANHYDRASE IS REQUIRED FOR STATOCONIA HOMEOSTASIS IN ORGAN-CULTURES OF STATOCYSTS FROM APLYSIA-CALIFORNICA SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE APLYSIA; CARBONIC ANHYDRASE; STATOCONIA; ORGAN CULTURE ID PARATHYROID-HORMONE; LOCALIZATION; OSTEOCLASTS; CALCITONIN AB A novel organ culture system has been developed to study the regulation of statoconia production in the gravity sensing organ in Aplysia californica. Statocysts were cultured in Leibovitz (L15) medium supplemented with salts and Aplysia haemolymph for four days at 17 degrees C. The viability of the system was evaluated by examining four parameters: statocyst morphology, the activity of the mechanosensory cilia in the statocyst, production of new statoconia during culture and change in statoconia volume after culture. There were no morphological differences in statocysts before and after culture when ciliary beating was maintained. There was a 29% increase in the number of statoconia after four days in culture. Mean statocyst, statolith and statoconia volumes were not affected by culture conditions. The presence of carbonic anhydrase in the statocysts was shown using immunohistochemistry. When statocysts were cultured in the presence of 4.0 x 10(-4) M acetazolamide to inhibit the enzyme activity, there was a decrease in statoconia production and statoconia volume, indicating a role for this enzyme in statoconia homeostasis, potentially via pH regulation. These studies are the first to report a novel system for the culture of statocysts and show that carbonic anhydrase is involved in the regulation of statoconia volume and production. C1 UNIV TEXAS,HLTH SCI CTR,DEPT ORTHOPAED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PERIODONT,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. HEBREW UNIV JERUSALEM,HADASSAH FAC DENT MED,DEPT PERIODONT,JERUSALEM,ISRAEL. OI Dean, David/0000-0002-4512-9065 FU NIDCR NIH HHS [DE05937] NR 23 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A-Sens. Neural Behav. Physiol. PD OCT PY 1995 VL 177 IS 4 BP 415 EP 425 PG 11 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA RU167 UT WOS:A1995RU16700004 PM 7674196 ER PT J AU Krolewski, AS Warram, JH AF Krolewski, AS Warram, JH TI Genetic susceptibility to diabetic kidney disease: An update SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article; Proceedings Paper CT 4th International Symposium on Hypertension Associated With Diabetes Mellitus, a Satellite Symposium of the 15th International-Diabetes-Federation Congress CY NOV 04-05, 1994 CL OTSU, JAPAN SP Int Diabet Federat ID SODIUM-LITHIUM COUNTERTRANSPORT; NA+/H+ ANTIPORT ACTIVITY; CULTURED SKIN FIBROBLASTS; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; INSULIN-RESISTANCE; RENAL-DISEASE; RISK FACTOR; RED-CELLS; NEPHROPATHY AB Various types of evidence supporting the hypothesis of genetic susceptibility to diabetic kidney disease (DKD) are reviewed. Three groups of studies were distinguished: (1) epidemiologic and family studies, (2) studies of phenotypic markers/predictors, and (3) studies of DNA markers. Although all of these studies point to the existence of susceptibility to DKD, further research is required, Particularly needed are studies that examine the mechanisms of interaction between genetic susceptibility to DKD and poor glycemic control, and studies to identify specific molecular mechanisms underlying this susceptibility. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP Krolewski, AS (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DEPT MED,RES DIV,SECT EPIDEMIOL & GENET,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK 41546] NR 49 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD OCT-DEC PY 1995 VL 9 IS 4 BP 277 EP 281 DI 10.1016/1056-8727(95)80021-6 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UA696 UT WOS:A1995UA69600021 PM 8573746 ER PT J AU TACHIBANA, K SATO, T DAVIRRO, N MORIMOTO, C AF TACHIBANA, K SATO, T DAVIRRO, N MORIMOTO, C TI DIRECT ASSOCIATION OF PP125(FAK) WITH PAXILLIN, THE FOCAL ADHESION-TARGETING MECHANISM OF PP125(FAK) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PROTEIN-TYROSINE KINASE; EXTRACELLULAR-MATRIX; SIGNAL TRANSDUCTION; INTEGRIN FAMILY; CELL-ADHESION; FIBRONECTIN; PHOSPHORYLATION; PP125FAK; VLA-4; IDENTIFICATION AB Focal adhesion kinase (pp125(FAK)) is localized to focal adhesions and tyrosine phosphorylated by the engagement of pi integrins. However, it is unclear how pp125(FAK) is linked to integrin molecules. We demonstrate that pp125(FAK) is directly associated with paxillin, a 68-kD cytoskeleton protein. The COOH-terminal domain of pp125(FAK) spanning FAK residues 919-1042 is sufficient for paxillin binding and has vinculin-homologous amino acids, which are essential for paxillin binding. Microinjection and subsequent immunohistochemical analysis reveal that glutathione S-transferase-FAK fusion proteins, which bind to paxillin, localize to focal adhesions, whereas fusion proteins with no paxillin-binding activity do not localize to focal adhesions. These findings strongly suggest that pp125(FAK) is localized to focal adhesions by the direct association with paxillin. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI29530]; NIAMS NIH HHS [AR33713] NR 40 TC 222 Z9 223 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1995 VL 182 IS 4 BP 1089 EP 1099 DI 10.1084/jem.182.4.1089 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RW879 UT WOS:A1995RW87900020 PM 7561682 ER PT J AU JENIKE, MA AF JENIKE, MA TI FUN-INDUCED HEADACHE SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD OCT PY 1995 VL 8 IS 4 BP 243 EP 243 PG 1 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA TE156 UT WOS:A1995TE15600009 ER PT J AU XIE, JL LI, R KOTOVUORI, P VERMOTDESROCHES, C WIJDENES, J ARNAOUT, MA NORTAMO, P GAHMBERG, CG AF XIE, JL LI, R KOTOVUORI, P VERMOTDESROCHES, C WIJDENES, J ARNAOUT, MA NORTAMO, P GAHMBERG, CG TI INTERCELLULAR-ADHESION MOLECULE-2 (CD102) BINDS TO THE LEUKOCYTE INTEGRIN CD11B/CD18 THROUGH THE A-DOMAIN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLEMENT RECEPTOR TYPE-3; FUNCTION-ASSOCIATED ANTIGEN-1; PLATELET GLYCOPROTEIN-IB; AMINO-ACID SEQUENCE; VONWILLEBRAND-FACTOR; MONOCLONAL-ANTIBODIES; COUNTER-RECEPTOR; ALPHA-SUBUNIT; CELL-ADHESION; MAC-1 CD11B/CD18 AB The interactions between the leukocyte-specific beta 2-integrins cluster of differentiation (CD) Ag CD11/CD18 and their ligands, the intercellular adhesion molecules (ICAMs), play important roles in many adhesion-dependent leukocyte functions. ICAM-1 is known to be a ligand for both CD11a/CD18 and CD11b/CD18. ICAM-2, whose two extracellular Ig domains show the highest homology to the two NH2-terminal domains of ICAM-1, has been previously shown to be a ligand for CD11a/CD18. We recently found that a 22-amino acid CD11a/CD18-binding peptide, P1, derived from the first domain of ICAM-2, also binds to purified CD11b/CD18. In the present study, we demonstrate that the ICAM-2 protein interacts with CD11b/CD18, and the binding is through the CD11b A domain. C1 HELSINKI UNIV,DEPT BIOSCI,DIV BIOCHEM,SF-00014 HELSINKI,FINLAND. MASSACHUSETTS GEN HOSP,DEPT MED,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Gahmberg, Carl/0000-0001-9892-9296 FU NHLBI NIH HHS [HL-51372, R01 HL-43773] NR 87 TC 82 Z9 82 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1995 VL 155 IS 7 BP 3619 EP 3628 PG 10 WC Immunology SC Immunology GA RV939 UT WOS:A1995RV93900044 PM 7561061 ER PT J AU MACLEAN, JA SU, ZL COLVIN, RB WONG, JT AF MACLEAN, JA SU, ZL COLVIN, RB WONG, JT TI ANTI-CD3-ANTI-IL-2 RECEPTOR-BISPECIFIC MAB-MEDIATED IMMUNOMODULATION - LOW SYSTEMIC TOXICITY, DIFFERENTIAL EFFECT ON LYMPHOID-TISSUE, AND INHIBITION OF CELL-MEDIATED HYPERSENSITIVITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID OKT3 MONOCLONAL-ANTIBODY; TUMOR-NECROSIS-FACTOR; INDIUM-111-LABELED DTPA DIMER; KIDNEY-TRANSPLANT RECIPIENTS; ALLOGRAFT SURVIVAL; T-CELLS; THYMOCYTES INVIVO; HUMAN-LYMPHOCYTES; RENAL-ALLOGRAFTS; CYTOKINE RELEASE AB An anti-CD3:anti-CD25 (CD3,25) bispecific mAb was developed with the objective of combining the advantages of the parent anti-CDS and anti-CD25 mAbs. The in vivo effects of the CD3,25 were examined in comparison to the parent Abs. The CD3,25 was well tolerated in vivo, in contrast to the parent anti-CDS mAb, which induced systemic toxicity in recipient animals. Anti-CD3 mAb induced cell death, lymphoblast formation, and T cell activation in peripheral lymphoid organs; these were observed to a lesser extent in CD3,25-treated animals. In the thymus, anti-CD3 caused a progressive depletion of the CD4(+)CD8(+) ''double positive'' thymocytes, which was not seen in CD3,25-treated animals. This finding suggests that monovalent CD3 binding is insufficient to induce thymocyte apoptosis. Animals treated with a combination of anti-CD3 and anti-CD25 mAbs demonstrated changes in the lymphoid organs that were similar to anti-CD3-treated mice. This finding demonstrates that the effect of the CD3,25 is different than the sum of the parent Abs and suggests that the bispecific nature of the CD3,25 results in a reagent with unique immunomodulatory properties. The functional efficacy of the CD3,25 was assessed in a murine model of delayed-type hypersensitivity. The CD3,25 was as effective as the anti-CD3 mAb in inhibiting the delayed-type hypersensitivity reaction and was more effective than the parent anti-CD25 mAb. These data demonstrate that appropriately designed bispecific mAbs can be used as effective immunosuppressive agents with low systemic toxicity. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CLIN IMMUNOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN MED SERV,ALLERGY UNIT,BOSTON,MA 02114. RP MACLEAN, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,IMMUNOPATHOL UNIT,COX 5,BOSTON,MA 02114, USA. FU NCI NIH HHS [5T32CA09216]; NHLBI NIH HHS [P01HL18646]; NIAID NIH HHS [R29AI27050] NR 48 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1995 VL 155 IS 7 BP 3674 EP 3682 PG 9 WC Immunology SC Immunology GA RV939 UT WOS:A1995RV93900051 PM 7561068 ER PT J AU MULLIGAN, LM MARSH, DJ ROBINSON, BG SCHUFFENECKER, L ZEDENIUS, J LIPS, CJM GAGEL, RF TAKAI, SL NOLL, WW FINK, M RAUE, F LACROIX, A THIBODEAU, SN FRILLING, A PONDER, BAJ ENG, C AF MULLIGAN, LM MARSH, DJ ROBINSON, BG SCHUFFENECKER, L ZEDENIUS, J LIPS, CJM GAGEL, RF TAKAI, SL NOLL, WW FINK, M RAUE, F LACROIX, A THIBODEAU, SN FRILLING, A PONDER, BAJ ENG, C TI GENOTYPE-PHENOTYPE CORRELATION IN MULTIPLE ENDOCRINE NEOPLASIA TYPE-2 - REPORT OF THE INTERNATIONAL-RET-MUTATION-CONSORTIUM SO JOURNAL OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 5th International Workshop on Multiple Endocrine Neoplasia CY JUN 29-JUL 02, 1994 CL STOCKHOLM, SWEDEN DE INHERITED CANCER SYNDROME; MEN 2; RET ID PROTOONCOGENE AB The International RET Mutation Consortium was first convened as part of the Fifth International Workshop on Multiple Endocrine Neoplasia, Stockholm, Sweden, in an attempt to analyse the relationship of RET mutation and disease phenotype in the autosomal dominantly inherited multiple endocrine neoplasia type 2 (MEN 2) syndromes. Out of 361 families studied, 41% had MEN 2A, 17.7% MEN 2B, 6.4% FMTC and the remaining subjects were unclassified, RET mutations were detected in 87.3% of families overall. Over 93% of MEN 2B families had the RET 918 ATG --> ACG mutation, while the most frequent mutation detected in MEN 2A families was cysteine codon 634 (87% of all mutations). C1 QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. ROYAL N SHORE HOSP,KOLLING INST MED RES,DEPT MOLEC GENET,ST LEONARDS,NSW 2065,AUSTRALIA. HOP EDOUARD HERRIOT,GENET LAB,LYON,FRANCE. KAROLINSKA HOSP,DEPT CLIN GENET & MOLEC MED,S-10401 STOCKHOLM,SWEDEN. UNIV UTRECHT HOSP,DEPT INTERNAL MED,CLIN GENET CTR,UTRECHT,NETHERLANDS. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX 77030. OSAKA UNIV,SCH MED,DEPT MED GENET,SUITA,OSAKA 565,JAPAN. DARTMOUTH COLL,HITCHCOCK MED CTR,DEPT PATHOL,LEBANON,NH 03756. UNIV VIENNA,SCH MED,DEPT SURG,VIENNA,AUSTRIA. UNIV HEIDELBERG,DEPT INTERNAL MED,W-6900 HEIDELBERG,GERMANY. HOP HOTEL DIEU,CTR RECH,DEPT ENDOCRINOL & MED,MONTREAL,PQ,CANADA. MAYO CLIN,DIV ENDOCRINOL,ROCHESTER,MN. UNIV HAMBURG HOSP,CHIRURG KLIN,W-2000 HAMBURG,GERMANY. ADDENBROOKES HOSP,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE,ENGLAND. HARVARD UNIV,SCH MED,DEPT MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. RP MULLIGAN, LM (reprint author), QUEENS UNIV,DEPT PAEDIAT,20 BARRIE ST,KINGSTON,ON K7L 3N6,CANADA. RI Marsh, Deborah/I-1491-2014; OI Marsh, Deborah/0000-0001-5899-4931; Eng, Charis/0000-0002-3693-5145 NR 7 TC 190 Z9 200 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD OCT PY 1995 VL 238 IS 4 BP 343 EP 346 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA TC660 UT WOS:A1995TC66000008 PM 7595170 ER PT J AU KIRTSCHIG, G MARINKOVICH, MP BURGESON, RE YANCEY, KB AF KIRTSCHIG, G MARINKOVICH, MP BURGESON, RE YANCEY, KB TI ANTIBASEMENT MEMBRANE AUTOANTIBODIES IN PATIENTS WITH ANTI-EPILIGRIN CICATRICIAL PEMPHIGOID BIND THE ALPHA-SUBUNIT OF LAMININ-5 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SKIN-DISEASE; COMPONENT; KALININ; LIGAND; ALPHA-3-BETA-1; KERATINOCYTES; PROTEINS; CELLS AB Recent studies have identified a group of cicatricial pemphigoid patients who have IgG anti-basement membrane autoantibodies that recognize epiligrin, a set of disulfide-linked polypeptides closely related if not identical to laminin 5 (formerly called kalinin, nicein, or BM600). To further understand the pathophysiology of blister formation in these patients, we have sought to identify the specific polypeptide(s) targeted by their autoantibodies. Comparative studies show that sera from these patients (nine of nine), P1E1 monoclonal anti-epiligrin antibody, and polyclonal as well as monoclonal anti-laminin 5 antibodies immunoprecipitate the same set of disulfide-linked polypeptides from media of biosynthetically radiolabeled human keratinocytes. Moreover, sera from eight of nine patients with anti-epiligrin cicatricial pemphigoid immunoblot the alpha subunit of laminin 5 but show no reactivity to its beta or gamma subunits. In addition, circulating IgG from a representative patient was affinity-purified against the alpha subunit of laminin 5 and shown to bind the dermal side of 1 M NaCl split skin in the same manner as autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid. Sera from patients with bullous pemphigoid (n = 5), other forms of cicatricial pemphigoid (n = 5), epidermolysis bullosa acquisita (n = 4), or bullous systemic lupus erythematosus (n = 1) show no reactivity against any subunit of this laminin isoform in immunoprecipitation or immunoblot experiments. These findings correlate with prior reports showing that a monoclonal antibody directed against the alpha subunit of laminin 5 (i.e., laminin subunit alpha 3) induces detachment of human keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these studies suggest that laminin subunit alpha 3 mediates attachment of basal keratinocytes to epidermal basement membrane and that autoantibodies directed against it may be pathogenic. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,SHRINERS HOSP CRIPPLED CHILDREN,DEPT DERMATOL,PORTLAND,OR 97201. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. FU NIAMS NIH HHS [AR 35689] NR 22 TC 143 Z9 146 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1995 VL 105 IS 4 BP 543 EP 548 DI 10.1111/1523-1747.ep12323431 PG 6 WC Dermatology SC Dermatology GA RY598 UT WOS:A1995RY59800004 PM 7561156 ER PT J AU KINOSIAN, B GLICK, H PREISS, L PUDER, KL AF KINOSIAN, B GLICK, H PREISS, L PUDER, KL TI CHOLESTEROL AND CORONARY HEART-DISEASE - PREDICTING RISKS IN MEN BY CHANGES IN LEVELS AND RATIOS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE CHOLESTEROL; CHD RISK; CORONARY PRIMARY PREVENTION TRIAL ID WOMEN; AREA AB Background: Little is known about the relative ability of different measures of change in cholesterol to discriminate coronary heart disease risk. We evaluated this ability for changes in low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, LDL/HDL ratios, and total cholesterol/HDL ratios. Methods: We predicted risks of coronary heart disease using data from 3641 men in the Lipid Research Clinics Coronary Primary Prevention Trial. Treating these patients as a cohort, we estimated risks associated with changes in cholesterol levels independent of the patients' randomization group. Results: Changes in LDL and HDL cholesterol when used in combination were each significant predictors of coronary heart disease risk (odds ratios [OR] for 10% increases, 1.15 and 0.84, respectively; P < 0.001). Changes in LDL/HDL and total cholesterol/HDL ratios had similar discriminating ability (OR for 10% increases, 1.17 and 1.21, respectively; P < 0.0001), In the best discriminating models, changes in ratios added information about risks to changes in LDL cholesterol, although changes in LDL cholesterol levels failed to add information to changes in ratios. Conclusions: Changes in total cholesterol/HDL and LDL/HDL ratios were better predictors of risk for coronary heart disease than were changes in LDL cholesterol levels alone. When assessed as percentage changes averaged during the first two months of intervention, they were among the best discriminators of risk. Clinicians selecting treatments for intervention should include among their considerations the treatment's effect on both LDL and HDL cholesterol rather than their effects on LDL cholesterol levels alone. C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. COLUMBIA UNIV,NEW YORK,NY. SANDOZ INC,PHARMACEUT,E HANOVER,NJ 07936. RP KINOSIAN, B (reprint author), UNIV PENN,DIV GEN INTERNAL MED,RALSTON PENN CTR,ROOM 302,3615 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. FU NIA NIH HHS [R29-AG09837-08] NR 15 TC 80 Z9 82 U1 1 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Investig. Med. PD OCT PY 1995 VL 43 IS 5 BP 443 EP 450 PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA TE359 UT WOS:A1995TE35900004 PM 8528755 ER PT J AU LIPTON, BA PARTHASARATHY, S ORD, VA CLINTON, SK LIBBY, P ROSENFELD, ME AF LIPTON, BA PARTHASARATHY, S ORD, VA CLINTON, SK LIBBY, P ROSENFELD, ME TI COMPONENTS OF THE PROTEIN-FRACTION OF OXIDIZED LOW-DENSITY-LIPOPROTEIN STIMULATE INTERLEUKIN-1-ALPHA PRODUCTION BY RABBIT ARTERIAL MACROPHAGE-DERIVED FOAM CELLS SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ATHEROSCLEROSIS; CHOLESTEROL-FED RABBIT ID SMOOTH-MUSCLE CELLS; MOUSE PERITONEAL-MACROPHAGES; FACTOR GENE-EXPRESSION; ATHEROSCLEROTIC LESIONS; MESSENGER-RNA; FAMILIAL HYPERCHOLESTEROLEMIA; ENDOTHELIAL-CELLS; LYSINE RESIDUES; POTENTIAL ROLE; BLOOD-PLASMA AB Oxidized low density lipoproteins (oxLDL) (0.5-50 mu g/ml) generated from both rabbit and human LDL stimulated the production of interleukin-1 alpha (IL-1 alpha) by as much as 2- and 6-fold, respectively, as compared to native LDL after a 2-h incubation with macrophage-derived foam cells isolated from the balloon-injured arteries of cholesterol-fed rabbits. Northern blot analyses confirmed that there was also an increase in the mRNA for IL-1 alpha and IL-beta in response to oxLDL in the isolated foam cells. The stimulation of IL-1 expression and production was not due to the contamination of the oxLDL preparations with endotoxin as neither the amount of endotoxin found to be associated with the lipoproteins nor amounts up to 1 ng/ml stimulated IL-1 alpha production to the same degree as oxLDL. Neither oxidized beta-very low density lipoprotein (VLDL) nor oxidized high density lipoprotein (HDL) stimulated IL-1 alpha production by the foam cells. Furthermore, acetyl-LDL had a very limited stimulatory effect, but other known ligands of the scavenger receptor such as maleylated-BSA, polyinosinic acid, and fucoidin elicited maximal IL-1 alpha responses. Fractionation of the oxLDL into lipid- and protein-soluble fractions showed that there was some stimulatory activity in the lipid phase but that known products of lipid peroxidation such as 9- and 13-HODE had no effect when added independently of lipoproteins. When added in combination with native LDL, only 13-HODE stimulated IL-1 alpha production. The delipidated apolipoprotein fragments of oxLDL that had been solubilized in beta-octylglucoside stimulated the production of IL-1 alpha by the foam cells to a greater degree than the lipid extract, while reductively methylated oxLDL did not. These data suggest that interactions of components of both the lipid- and protein-soluble fractions of oxLDL with scavenger receptors or potentially with surface proteins that bind oxLDL may induce production of IL-1 by arterial macrophages. C1 UNIV WASHINGTON,DEPT PATHOBIOL,SEATTLE,WA 98195. UNIV WASHINGTON,PROGRAM NUTR SCI,SEATTLE,WA 98195. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. EMORY UNIV,DEPT GYNECOL & OBSTET,ATLANTA,GA 30322. DANA FARBER CANC INST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RI Parthasarathy, Sampath/G-5602-2011 FU NHLBI NIH HHS [HL14197, HL42617] NR 59 TC 34 Z9 34 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD OCT PY 1995 VL 36 IS 10 BP 2232 EP 2242 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TB906 UT WOS:A1995TB90600016 PM 8576649 ER PT J AU LINGGOOD, RM HSU, DW EFIRD, JT PARDO, FS AF LINGGOOD, RM HSU, DW EFIRD, JT PARDO, FS TI TGF-ALPHA EXPRESSION IN MENINGIOMA - TUMOR PROGRESSION AND THERAPEUTIC RESPONSE SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE MENINGIOMA; TGF ALPHA; TUMOR PROGRESSION ID RADIATION-THERAPY; GROWTH; RECURRENCE; MANAGEMENT; RESECTION; CELLS AB Little is known of the molecular genetic mechanisms contributing to meningioma tumor progression. We evaluated a total of 26 clinical cases of meningioma: twenty three patients with meningioma treated at our institution between 1978 and 1990 and three asymptomatic cases found initially at autopsy. In addition, histologically normal meninges obtained at post-mortem examination from 5 cases were evaluated. There were 13 men and 10 women in the patient group with a median age of 48.7 years, treated by surgery and/or irradiation. Median follow-up was 46 months (range 16-152 months). Archival cases and age-matched normal meningeal tissue obtained at autopsy during the same time period were obtained for study. Patients with TGF alpha scores greater than 3.0 were more likely to fail treatment and had lower overall survival times than those with immunostaining scores of 1 or 2. Three autopsy cases where meningioma had been silent clinically had overall staining scores of 0.75, while 10 samples of normal meninges harvested from 5 cases at autopsy had staining scores of 0. Two patients each underwent 3 surgeries for recurrent tumor, serial specimens showed increased TGF alpha expression over time, though all material from these procedures was consistent with the diagnosis of histologically benign meningioma. C1 MASSACHUSETTS GEN HOSP,MOLEC TUMOR RADIAT BIOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV NEUROPATHOL,BOSTON,MA 02114. DEPT RADIAT ONCOL,DIV BIOSTAT,BOSTON,MA. NR 17 TC 17 Z9 17 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD OCT PY 1995 VL 26 IS 1 BP 45 EP 51 DI 10.1007/BF01054768 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA TD920 UT WOS:A1995TD92000006 PM 8583244 ER PT J AU NAGY, AK SHUSTER, TA AF NAGY, AK SHUSTER, TA TI ATP-BINDING PROTEINS ON THE EXTERNAL SURFACE OF SYNAPTIC PLASMA-MEMBRANES - IDENTIFICATION BY PHOTOAFFINITY-LABELING SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE EXTRACELLULAR ATP; PRESYNAPTIC ECTO-ATP-BINDING SITES; AZIDO-ATP BINDING ID TORPEDO ELECTRIC ORGAN; SARCOPLASMIC-RETICULUM; EXTRACELLULAR ATP; ECTO-ATPASE; SYNAPTOSOMES; 8-AZIDO-ATP; ADENOSINE; SITES; CELLS; HYDROLYSIS AB 8-Azidoadenosine triphosphate labeled in the alpha or gamma position with P-32 was used as a photoaffinity reagent for identifying ATP binding sites on the external surface of intact rat brain synaptosomes. As revealed by autoradiography of sodium dodecyl sulfate-polyacrylamide gel electrophoretic patterns, UV irradiation of intact synaptosomes in the presence of the above radioactive compounds at 5-10 mu M resulted in the formation of several major radioactive conjugates with approximate molecular masses of 29, 45/46, 58, and 93 kDa, Minor bands of 20, 39, 52/54, 82/84, 120, and 140 kDa were also consistently labeled in these experiments. The possibility that labeling of these proteins was due to the presence of contaminating subcellular particles or intrasynaptosomal proteins was excluded. The major 8-azidoadenosine [alpha-P-32]triphosphate-labeled protein complex of similar to 45/46 kDa was resolved into several subbands that are labeled differently depending on the type of divalent cations added to the photoaffinity reaction, In the presence of magnesium only, the major labeled band appeared at 45 kDa. With calcium, two additional subbands (43 and 46 kDa) could be distinguished. In the presence of 1 mM EDTA, a band at 44 kDa was labeled within this ATP-binding complex, The labeling pattern of the subbands of this 45/46-kDa complex is consistent with these bands being extracellular ATP-binding proteins on the surface of the synaptosome. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. CALIF STATE UNIV LONG BEACH,DEPT BIOL SCI,LONG BEACH,CA 90840. FU NINDS NIH HHS [NS 21908] NR 42 TC 8 Z9 8 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1995 VL 65 IS 4 BP 1849 EP 1858 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RW335 UT WOS:A1995RW33500049 PM 7561884 ER PT J AU MCCUE, MP GUINAN, JJ AF MCCUE, MP GUINAN, JJ TI SPONTANEOUS ACTIVITY AND FREQUENCY-SELECTIVITY OF ACOUSTICALLY RESPONSIVE VESTIBULAR AFFERENTS IN THE CAT SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INNERVATING OTOLITH ORGANS; AUDITORY-NERVE FIBERS; COCHLEAR HAIR-CELLS; SQUIRREL-MONKEY; OLIVOCOCHLEAR NEURONS; EVOKED-POTENTIALS; TUNING CURVES; STATIC TILTS; PHYSIOLOGY; DESTRUCTION AB 1. Recordings were made from single afferent fibers in the inferior vestibular nerve. Firing rates of a substantial portion of the afferents with irregular background activity increased in response to moderately intense tone bursts. 2. Spontaneous activity from acoustically responsive vestibular afferents was statistically analyzed and compared with data from a more widespread sampling of primary afferents in the cat's vestibulocochlear nerve. Acoustically responsive vestibular afferents had interspike interval histograms with modes >10 ms, coefficients of variation >0.15, and skews >0.88. On the basis of spontaneous activity, these afferents were easily distinguishable from cochlear afferents and regular vestibular afferents, but no obvious features differentiated them from other irregular vestibular afferents. 3. The distributions of spike intervals in the spontaneous activity of acoustically responsive vestibular afferents were fitted by Erlang probability density functions describing the second-order interarrival times of a Poisson process initiated after a finite delay (refractory period). 4. Acoustically responsive vestibular afferents had broad, V-shaped tuning curves with best frequencies between 500 and 1,000 Hz, thresholds of greater than or equal to 90 dB SPL, and shapes comparable with the tuning-curve ''tails'' of cochlear afferents. In contrast to cochlear-nerve afferents, acoustically responsive vestibular afferents did not show a strong relationship between spontaneous rate and threshold. 5. We compare the acoustic frequency selectivity of vestibular and cochlear afferents in terms of their functional and evolutionary relationships. Our data and those of others indicate that acoustically responsive vestibular afferents are likely to provide an input to the acoustic activation of the sternocleidomastoid muscle in humans, and they may provide an input to other acoustic reflexes such as the middle-ear-muscle reflexes. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. HARVARD MIT DIV HLTH SCI & TECHNOL,ELECTR RES LAB,CAMBRIDGE 02139,ENGLAND. MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. FU NIDCD NIH HHS [R01-DC00235, T32-DC0006] NR 56 TC 61 Z9 66 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 1995 VL 74 IS 4 BP 1563 EP 1572 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA TA401 UT WOS:A1995TA40100017 PM 8989393 ER PT J AU SCHMIDT, B KEARNS, G PERROTT, D KABAN, LB AF SCHMIDT, B KEARNS, G PERROTT, D KABAN, LB TI INFECTION FOLLOWING TREATMENT OF MANDIBULAR FRACTURES IN HUMAN-IMMUNODEFICIENCY-VIRUS SEROPOSITIVE PATIENTS SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; HIV-INFECTION; MONOCYTE FUNCTION; AIDS; SURGERY; DYSFUNCTION; IMPAIRMENT; CHEMOTAXIS; DISORDERS; ETIOLOGY AB Purpose: There are little data available on the prevalence of human immunodeficiency virus (HIV) disease and its relationship to postoperative infection in patients presenting with mandibular fractures, This retrospective study assesses these parameters, Patients: The study population consisted of 251 patients treated for mandibular fractures at San Francisco General Hospital (SFGH) between January 1990 and December 1993, Group I (n = 20) was composed of patients with documented HIV infection and group 2 (n = 231) served as controls. The groups were comparable with regard to age, sex, etiology, and number and types of fractures. Results, HIV prevalence for this population was 7.9%, and was consistent with previously documented prevalence studies in SFGH surgical patients. In the HIV-positive group, 6 of 20 patients (30%) developed postoperative infection: 2 soft tissue (10%) and 4 bone-related (20%). In the control group, 22 of 231 patients (9.5%) developed postoperative infections: 16 soft tissue (6.9%) and 6 bone-related (2.6%), Statistical analysis showed a significant difference between the two groups with regard to overall (P = .016) and to bone-related (P = .001) infection rates. There was no statistically significant difference in soft tissue infections between the two groups (P = .953). The rate of postoperative infection was significantly higher in those patients (both HIV-positive and controls) who had open reduction and internal fixation (ORIF; 25/155; 16%) versus those who had closed reduction and maxillomandibular fixation (3/96; 3.1%; P = .003), The postoperative infection rate after ORIF was significantly higher in the HIV-positive (5/11, 45%) compared with the control group (20/144; 13.9%; P = .02). Conclusions: The results of this study indicate that the overall rate of postoperative infection after treatment of mandibular fractures is significantly higher in HIV-positive than in HIV-negative patients. Specifically, the use of ORIF in HIV-positive patients represents a significant risk. C1 UNIV CALIF SAN FRANCISCO,DEPT ORAL & MAXILLOFACIAL SURG,SAN FRANCISCO,CA 94143. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02115. OI Schmidt, Brian/0000-0002-2409-8984 NR 33 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 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD OCT PY 1995 VL 53 IS 10 BP 1134 EP 1139 DI 10.1016/0278-2391(95)90618-5 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RX416 UT WOS:A1995RX41600002 PM 7562164 ER PT J AU AVELINE, BM HASAN, T REDMOND, RW AF AVELINE, BM HASAN, T REDMOND, RW TI THE EFFECTS OF AGGREGATION, PROTEIN-BINDING AND CELLULAR INCORPORATION ON THE PHOTOPHYSICAL PROPERTIES OF BENZOPORPHYRIN DERIVATIVE MONOACID RING-A (BPDMA) SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE BENZOPORPHYRIN DERIVATIVE; AGGREGATION; PROTEIN BINDING; PHOTOPHYSICS; PHOTOSENSITIZER ID HUMAN-SERUM-ALBUMIN; PORPHYRIN SELF-AGGREGATION; PHOTODYNAMIC THERAPY; QUANTUM YIELDS; HEMATOPORPHYRIN; EQUILIBRIUM; HEMOPEXIN; PROTOPORPHYRIN; FLUORESCENCE; BENZOPHENONE AB Absorption, fluorescence and laser flash photolysis spectroscopies were used to investigate the effects of self-aggregation, binding to human serum albumin and incorporation in cancer cells on the photophysics of benzoporphyrin derivative monoacid ring A (BPDMA). Aggregation of BPDMA has been studied in mixtures of methanol and phosphate-buffered saline (PBS). The extent of aggregation was dependent on dye concentration and solvent composition, becoming particularly marked in mixtures containing less than 30% methanol. A dimerization constant K-d or 9 X 10(6) M(-1) was determined by fluorescence experiments for BPDMA in pure PBS. In addition to spectral modifications, aggregation induces a lowering of the fluorescence and intersystem crossing quantum yields. Human serum albumin binds BPDMA with an association constant K-b of 5.2 X 10(5) M(-1) in PBS. When bound to HSA, BPDMA displays photophysical properties very similar to the monomer in organic solvents. The molar ratio [HSA]/[BPDMA] corresponding to complete binding of the dye was determined to be approximately 10. Efficient generation of the triplet state of BPDMA was also observed from aqueous cellular suspensions containing incorporated photosensitizer. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. FU NIAMS NIH HHS [AR 38918] NR 35 TC 145 Z9 152 U1 2 U2 13 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD OCT PY 1995 VL 30 IS 2-3 BP 161 EP 169 DI 10.1016/1011-1344(95)07174-Z PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TH977 UT WOS:A1995TH97700011 PM 8558368 ER PT J AU RILEY, PO BENDA, BJ GILLBODY, KM KREBS, DE AF RILEY, PO BENDA, BJ GILLBODY, KM KREBS, DE TI PHASE PLANE ANALYSIS OF STABILITY IN QUIET STANDING SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE BALANCE; CENTER OF GRAVITY; CENTER OF PRESSURE; FORCE PLATES; PHASE PLANE; POSTURE; VESTIBULAR ID DYNAMIC POSTUROGRAPHY; BODY SWAY; BALANCE; POSTURE; ORGANIZATION; STANCE; REHABILITATION; DIZZINESS; CHILDREN AB We analyzed the standing balance control of 11 healthy subjects and 15 subjects with bilateral vestibular hypofunction (BVH) using phase plane (velocity versus displacement) plots. We hypothesized that maintaining postural stability requires control of both the position and momentum of the center of gravity (CG) and infer that it is advantageous to use both velocity and displacement data to characterize balance control. Phase balance control We evaluated phase plane plots based on whole body CG and center of pressure (CoP). We varied stability by altering the base of support and visual information. Three different foot placements were used: feet wide apart, feet together, and semitandem stance. Feet together standing was performed with eyes open and with eyes closed. The phase plane plots show changes in stability as base of support is altered or visual input is removed and reveal stability differences between the control and BVH groups. The root mean square variance of velocity and displacement was used to quantity the phase plane information. This parameter showed significant differences between activities and between groups. We conclude that phase plane plots that combine displacement and velocity information are more useful in characterizing balance control than displacement or velocity alone. RP RILEY, PO (reprint author), MASSACHUSETTS GEN HOSP,BIOMOT LAB,RUTH SLEEPER HALL,RM 010,40 PARKMAN ST,BOSTON,MA 02114, USA. RI Riley, Patrick/B-3053-2009 NR 26 TC 70 Z9 70 U1 2 U2 16 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 SN 0007-506X J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD OCT PY 1995 VL 32 IS 3 BP 227 EP 235 PG 9 WC Rehabilitation SC Rehabilitation GA TC481 UT WOS:A1995TC48100007 PM 8592294 ER PT J AU WALLACE, HJ WILLETT, CG SHELLITO, PC COEN, JJ HOOVER, HC AF WALLACE, HJ WILLETT, CG SHELLITO, PC COEN, JJ HOOVER, HC TI INTRAOPERATIVE RADIATION-THERAPY FOR LOCALLY ADVANCED RECURRENT RECTAL OR RECTOSIGMOID CANCER SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE RECTAL CARCINOMA; LOCAL FAILURE; SALVAGE; RADIATION THERAPY ID PELVIC EXENTERATION; COLORECTAL-CANCER; SACRAL RESECTION; CURATIVE SURGERY; RADICAL SURGERY; CARCINOMA; IRRADIATION; ADENOCARCINOMA; RADIOTHERAPY; FAILURE AB Recurrent rectal or rectosigmoid cancer is a difficult therapeutic problem. A treatment program of external beam irradiation, surgery, and intraoperative irradiation has been used for 41 patients. The 5-year actuarial local control and disease-free survival of all 41 patients was 30% and 16%, respectively. Subset analysis demonstrated differences in outcome by extent of surgical resection. The 5-year actuarial local control and disease-free survival of 27 patients undergoing complete resection was 47% and 21%, respectively. By contrast, the outcome of 14 patients undergoing partial resection was poor, with a 5-year actuarial local control and survival of 21% and 7%, respectively. Late complications included soft tissue or peripheral nerve injury, with many of these resolving within 4-18 months. Local control and disease-free survival rates are favorable in comparison with the results achieved by aggressive surgery. Patients who achieve a gross total resection at intraoperative irradiation have a markedly better prognosis than that of patients with residual gross disease. (C) 1995 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,COX CANC CTR,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 36 TC 53 Z9 53 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT PY 1995 VL 60 IS 2 BP 122 EP 127 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA RZ786 UT WOS:A1995RZ78600010 PM 7564378 ER PT J AU LEINBACH, RC AF LEINBACH, RC TI DILATED CARDIOMYOPATHY - TO PACE OR NOT TO PACE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CHAMBER RP LEINBACH, RC (reprint author), MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1995 VL 26 IS 4 BP 974 EP 974 DI 10.1016/0735-1097(95)00348-2 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RX427 UT WOS:A1995RX42700021 PM 7560626 ER PT J AU SONG, MK ADHAM, NF HENG, MCY COSTEA, NV HENG, MK AMENT, ME AF SONG, MK ADHAM, NF HENG, MCY COSTEA, NV HENG, MK AMENT, ME TI METABOLIC ALTERATIONS OF ZINC AND PROSTAGLANDINS IN BOTH HUMAN AND ANIMAL COLONIC TUMOR-CELLS SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE COLONIC NEOPLASMS; ZINC; PROSTAGLANDINS; RAT; PROSTAGLANDIN SYNTHASE ID LARGE-BOWEL CANCER; ASPIRIN USE; CROHNS-DISEASE; DIETARY ZINC; F344 RATS; RISK; GROWTH; CARCINOGENESIS; CYCLOOXYGENASE; DEFICIENCY AB Objective: To understand the relationship between zinc and prostaglandin (PG) metabolisms in inducing colon cancer incidence in human and animals. Methods: Human colonic tumor and normal cells were obtained from Departments of Surgery and Pathology at the Kaiser Permanente Medical Center, Los Angeles, CA and US VA Medical Center, North Hills, CA. Rat colonic tumor and normal cells were isolated from the rats that received two injections of 50 mg/kg of Azoxymethan (AOM) in 2 weeks and then kept 30 weeks in the animal facility. Then, the effects of zinc on the PGE(2) synthesis and PGE(2) on zinc metabolism in tumor and normal cells were determined. Results: PGE(2) concentrations in both human and AOM-induced rat colonic tumor cells increased compared to those in adjacent normal colonocytes, whereas PGF(2 alpha) concentrations did not change. Gene expression of inducible form of prostaglandin synthase (PGS-2) is stimulated in rat colonocytes by epidermal growth factor and by tetradecanoyl 13-phorbol acetate (a tumor promoter and mitogen) only in the presence of zinc, PGE(2) binding activity of rat enterocytes was maximum at 15 mu M of zinc (normal plasma zinc concentration), but PGE(2), synthesis activity increased for the first 15 minutes when extracellular zinc concentrations were either higher or lower than the normal extracellular zinc concentration. However, variations in extracellular zinc concentrations did not change the rate of PGF(2 alpha) synthesis in the normal rat enterocytes. PGE(2) significantly increased zinc uptake rates of colonic tumor cells but PGF(2 alpha) showed only moderate effect. Conclusions: These results suggest that zinc is required for PGS-2 gene expression, that maintaining an optimal zinc nutriture is important for normal PG synthesis of intestinal cells, and that only PGE(2) synthesis mechanisms rather than PGS-2 gene expression are altered in colonic tumor cells resulting in the abnormal zinc nutriture of these cells. C1 SEPULVEDA VA MED CTR, NORTH HILLS, CA USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA 90073 USA. NR 42 TC 2 Z9 2 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0731-5724 EI 1541-1087 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD OCT PY 1995 VL 14 IS 5 BP 473 EP 479 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RX307 UT WOS:A1995RX30700011 PM 8522726 ER PT J AU GHUSN, HF TEASDALE, TA SKELLY, JR AF GHUSN, HF TEASDALE, TA SKELLY, JR TI LIMITING TREATMENT IN NURSING-HOMES - KNOWLEDGE AND ATTITUDES OF NURSING-HOME MEDICAL DIRECTORS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Note ID CARDIOPULMONARY-RESUSCITATION; CARE; OUTCOMES; CPR; FACILITY AB OBJECTIVE: To determine nursing home medical directors' knowledge about cardiopulmonary resuscitation outcome and their support of treatment limitation requests and policies. DESIGN: Mailed questionnaire, followed by telephone interview. PARTICIPANTS: Forty-six medical directors of 70 community nursing homes in Harris County, Texas. MEASUREMENTS: Medical directors were asked to estimate the CPR survival rate to discharge of all nursing home residents and that of two case scenarios. They were asked to indicate on a Likert scale their support for mandatory Do-Not-Resuscitate orders and for requests by nursing home patients to withhold other life support measures. RESULTS: Responses were received from 33 directors. Overall CPR survival rate of older nursing home residents after cardiac arrest was thought to be 10.7%. The average CPR survival rate for healthy older people with witnessed arrests was believed to be 13.8%. The perceived rate for unwitnessed arrests in terminal patients was 4.6%, significantly lower than estimates for healthy older people (P = .003) and estimates of the overall survival rate (P = .02). Medical directors were split regarding mandatory Do-Not-Resuscitate orders for patients in vegetative states, with terminal illness, with an unwitnessed arrest, or in those older than 90 years of age. Mandatory use of Do-Not-Resuscitate orders for all nursing home residents was strongly opposed. Assuming a 2% survival rate did not significantly influence medical directors' opinions about mandatory DNR orders in these groups. Medical directors were more willing to support requests by stable nursing home residents to withhold resuscitation, mechanical ventilation, or hospitalization than requests to withhold antibiotics, intravenous fluids, or tube feedings (P < .005). The majority of medical directors were willing to withhold all such measures for terminal patients. CONCLUSIONS: Health care professionals who are responsible for educating patients about the efficacy of cardiopulmonary resuscitation in nursing homes overestimate its benefit and may benefit from further education about its outcome. Although mandatory Do-Not-Resuscitate orders were favored for terminal or vegetative patients, medical directors are not supportive of such orders across the board. Medical directors are more willing to honor requests for treatment limitation by terminal patients than others. C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. RP GHUSN, HF (reprint author), HOUSTON VET AFFAIRS MED CTR,GERIATR & EXTENDED CARE SERV 110,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 13 TC 10 Z9 10 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 1995 VL 43 IS 10 BP 1131 EP 1134 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RY285 UT WOS:A1995RY28500011 PM 7560705 ER PT J AU HUTCHISON, FN CUI, XY WEBSTER, SK AF HUTCHISON, FN CUI, XY WEBSTER, SK TI THE ANTIPROTEINURIC ACTION OF ANGIOTENSIN-CONVERTING ENZYME IS DEPENDENT ON KININ SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE PROTEINURIA; NEPHROTIC SYNDROME; BRADYKININ; KALLIKREIN; KININ ANTAGONIST ID PASSIVE HEYMANN NEPHRITIS; LIMITS GLOMERULAR INJURY; II RECEPTOR BLOCKADE; REDUCED RENAL MASS; BRADYKININ-ANTAGONIST; DIETARY-PROTEIN; INHIBITION; RATS; MODULATION; HYPERTENSION AB Converting enzyme inhibitors (CEI) reduce proteinuria in nephrotic humans and animals, but the mediator(s) of this effect has not been identified definitively. To determine whether enhanced kinin activity contributes to the antiproteinuric action of CEI, rats with passive Heymann nephritis were treated with the B-2 kinin receptor antagonist HOE 140, 300 mu g/kg per day, for 3 days and then the CEI enalapril (ENAL), 35 mg/kg per day, was given for another 4 days while HOE 140 was continued (HOE/ENAL). Additional groups of nephrotic rats were untreated (CON), received HOE 140 only (HOE), or received ENAL only. ENAL alone produced a >60% decrease in albuminuria after 4 days, whereas HOE 140 alone had no effect on albuminuria. In HOE/ENAL, pretreatment with HOE 140 prevented the decrease in albuminuria observed in ENAL. GFR increased significantly over time in all groups but was not different among the groups on any day. The clearance of albumin decreased significantly in ENAL (P <0.001) and was significantly lower than in CON, HOE, or HOE/ENAL on Day 10. The fractional clearance of albumin decreased in all groups as a result of the increase in GFR but was significantly lower in ENAL compared with the other three groups at Day 10 and was not different between CON, HOE, and HOE/ENAL. Plasma renin activity and concentration were increased significantly in both ENAL and HOE/ENAL, indicating that converting enzyme was effectively inhibited in both groups. It was concluded that enhanced kinin activity contributes to the antiproteinuric action of CEI in this model of nephrotic syndrome. C1 MED UNIV S CAROLINA,DIV NEPHROL,CHARLESTON,SC. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. FU NIDDK NIH HHS [DK-43185] NR 24 TC 35 Z9 36 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1995 VL 6 IS 4 BP 1216 EP 1222 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA TB912 UT WOS:A1995TB91200012 PM 8589289 ER PT J AU ESTROFF, JA PARAD, RB BARNES, PD MADSEN, JP BENACERRAF, BR AF ESTROFF, JA PARAD, RB BARNES, PD MADSEN, JP BENACERRAF, BR TI POSTERIOR-FOSSA ARACHNOID CYST - AN IN-UTERO MIMICKER OF DANDY-WALKER MALFORMATION SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Note C1 CHILDRENS HOSP,DEPT NEUROSURG,BOSTON,MA 02115. CHILDRENS HOSP,DIV NEWBORN MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA. RP ESTROFF, JA (reprint author), CHILDRENS HOSP,DEPT RADIOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. RI Parad, Richard/E-8559-2010 NR 13 TC 5 Z9 6 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD OCT PY 1995 VL 14 IS 10 BP 787 EP 790 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA RX392 UT WOS:A1995RX39200015 PM 8544249 ER PT J AU MCDOUGAL, WS AF MCDOUGAL, WS TI CARCINOMA OF THE PENIS - IMPROVED SURVIVAL BY EARLY REGIONAL LYMPHADENECTOMY BASED ON THE HISTOLOGICAL GRADE AND DEPTH OF INVASION OF THE PRIMARY LESION SO JOURNAL OF UROLOGY LA English DT Article DE PENIS; NEOPLASM STAGING; LYMPH NODE AB Purpose: This study was performed to validate a new staging system and support the concept of early regional lymphadenectomy based on this system. Materials and Methods: A total of 76 cases from 4 teaching hospitals was reviewed. Results: Of 24 patients with well or moderately differentiated noninvasive primary tumors 1 had regional metastases compared to 43 of 52 patients with poorly differentiated or invasive tumors. Conclusions: By classifying disease according to the depth of invasion and degree of differentiation of the primary lesions a high degree of accuracy could be obtained in predicting the likelihood of positive groin nodes. Removing groin nodes that are microscopically positive improves the survival rate over that of delayed lymphadenectomy. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114, USA. NR 10 TC 138 Z9 143 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 1995 VL 154 IS 4 BP 1364 EP 1366 DI 10.1016/S0022-5347(01)66863-0 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA RU472 UT WOS:A1995RU47200026 PM 7658539 ER PT J AU YAO, F SCHAFFER, PA AF YAO, F SCHAFFER, PA TI AN ACTIVITY SPECIFIED BY THE OSTEOSARCOMA LINE U2OS CAN SUBSTITUTE FUNCTIONALLY FOR ICP0, A MAJOR REGULATORY PROTEIN OF HERPES-SIMPLEX VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; IMMEDIATE-EARLY POLYPEPTIDES; CELL-CYCLE; MESSENGER-RNA; MACROMOLECULAR-SYNTHESIS; SUSCEPTIBILITY GENE; VIRAL POLYPEPTIDES; TRANS-ACTIVATION; DELETION MUTANTS; BINDING-PROTEIN AB Among the five immediate-early regulatory proteins of herpes simplex virus (HSV) type 1, only ICP0 is capable of activating all kinetic classes of viral genes. Consistent with its broad transactivating activity, ICP0 plays a major role in enhancing the reactivation of HSV from latency both in vivo and in vitro. Although not essential for viral replication, ICP0 confers a significant growth advantage on the virus, especially at low multiplicities of infection. In this report we describe the expression of a novel activity by the osteosarcoma cell line U2OS that can substitute functionally for ICP0. Compared with Vero cells, both U2OS cells and cells of the ICP0-expressing line 0-28 significantly enhanced the plating efficiency of an ICP0 null mutant, 7134. In contrast, the plating efficiencies of the wild-type virus in all three cell types were similar. Single-step growth experiments demonstrated that the yield of 7134 in U2OS cells was severalfold higher than that in 0-28 cells and about 100-fold higher than that in Vero cells, In order to identify the viral genes whose expression is enhanced by the activity in U2OS cells, levels of expression of selected viral proteins in extracts of Vero and U2OS cells were compared by Western blot (immunoblot) analysis following low-multiplicity infection. At a multiplicity of 0.1 PFU per cell, the levels of expression of the immediate-early protein ICP4 and the early protein go in 7134-infected U2OS cells were significantly higher than those in 7134-infected Vero cells. When infections were carried out at a multiplicity of 1 PFU per cell, however, no major differences in the levels of expression of these proteins in U2OS and Vero cells were observed. Cycloheximide reversal experiments demonstrated that the cellular activity expressed in U2OS cells that promotes high-level expression of ICP4 is not synthesized de novo but appears to exist as a preformed protein(s). To confirm this observation and to determine whether, like immediate-early genes, early, delayed-early, and late viral genes are also responsive to the cellular activity, transient-expression assays were performed. The results of these tests demonstrated that basal levels of expression from immediate-early, early, and delayed-early promoters, but not that from a late promoter, were significantly higher in U2OS cells than in Vero cells and that this enhancement occurred in the absence of viral proteins. Mutational analysis of the ICP4 promoter, the most responsive of the HSV type 1 promoters tested, has shown that the 139-bp sequence between the SphI and SacII sites is required for the high basal level of expression of ICP4 in U2OS cells. C1 DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NCI NIH HHS [R37CA20260]; NCRR NIH HHS [SO7RR05526-30] NR 74 TC 133 Z9 133 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1995 VL 69 IS 10 BP 6249 EP 6258 PG 10 WC Virology SC Virology GA RU784 UT WOS:A1995RU78400036 PM 7666525 ER PT J AU KIEBEREMMONS, T LIN, CM PRAMMER, KV VILLALOBOS, A KOSARI, F KLEYMAN, TR AF KIEBEREMMONS, T LIN, CM PRAMMER, KV VILLALOBOS, A KOSARI, F KLEYMAN, TR TI DEFINING TOPOLOGICAL SIMILARITIES AMONG ION-TRANSPORT PROTEINS WITH ANTI-AMILORIDE ANTIBODIES SO KIDNEY INTERNATIONAL LA English DT Article ID EPITHELIAL SODIUM-CHANNEL; EXCHANGER ISOFORM NHE-2; NA+/H+ EXCHANGER; EXPRESSION CLONING; DISTINCT EPITOPES; INTRACELLULAR PH; BINDING-PROTEIN; INHIBITION; ANALOGS; CDNA AB The structural features of amiloride binding sites an amiloride-sensitive transport proteins have received limited characterization. An antibody that recognizes limited regions of amiloride and can mimic, in binding specificity, certain amiloride-sensitive transport proteins was used as a model to elucidate potential amino acid residue relationships that might define putative amiloride contact sites. Analysis of the structure of this antibody has allowed us to identify sequence relationships among several Na+ selective transport proteins. A structure-based relational database was employed to re-examine sequence homologies among these ion transport proteins. A search of the protein sequence databank identified representative amino acid tracts among amiloride sensitive proteins involving planar residues that might be involved in interacting with amiloride. Computer models of sites within transmembrane domains of NHE1 and MHE2 isoforms of the Na+/H+ exchanger reflective of these planar tracts indicate that amiloride probably spans two helices for interaction with the Na+/H+ exchanger. Structural analysis of this monoclonal anti-amiloride antibody appears to mimic some of the salient features of amiloride binding sites on these proteins. C1 UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT BIOPHYS,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP KIEBEREMMONS, T (reprint author), UNIV PENN,DEPT PATHOL & LAB MED,ROOM 267 JOHN MORGAN,PHILADELPHIA,PA 19104, USA. FU NHLBI NIH HHS [HL07027] NR 48 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1995 VL 48 IS 4 BP 956 EP 964 DI 10.1038/ki.1995.377 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA RV926 UT WOS:A1995RV92600007 PM 8569105 ER PT J AU CANTIELLO, HF AF CANTIELLO, HF TI ROLE OF THE ACTIN CYTOSKELETON ON EPITHELIAL NA+ CHANNEL REGULATION SO KIDNEY INTERNATIONAL LA English DT Article ID PROTEIN KINASE-A; SODIUM-CHANNEL; F-ACTIN; BINDING-PROTEIN; CYTOCHALASIN-D; CELL-VOLUME; KIDNEY-CELLS; K+ CHANNEL; FILAMENTS; POLYMERIZATION AB The regulatory role of actin filament organization on epithelial Na+ channel activity is reviewed in this report. The actin cytoskeleton, consisting of actin filaments and associated actin-binding proteins, is essential to various cellular events including the maintenance of cell shape, the onset of cell motility, and the distribution and stability of integral membrane proteins. Functional interactions between the actin cytoskeleton and specific membrane transport proteins are, however, not as well understood. Recent studies from our laboratory have determined that dynamic changes in the actin cytoskeletal organization may represent a novel signaling mechanism in the regulation of ion transport in epithelia. This report summarizes work conducted in our laboratory leading to an understanding of the molecular steps associated with the regulatory role of the actin-based cytoskeleton on epithelial Nac channel function. The basis of this interaction lies on the regulation by actin-binding proteins and adjacent structures, of actin filament organization which in turn, modulates ion channel activity. The scope of this interaction may extend to such relevant cellular events as the vasopressin response in the kidney. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NR 90 TC 98 Z9 103 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1995 VL 48 IS 4 BP 970 EP 984 DI 10.1038/ki.1995.379 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA RV926 UT WOS:A1995RV92600009 PM 8569107 ER PT J AU VERKMAN, AS SHI, LB FRIGERI, A HASEGAWA, H FARINAS, J MITRA, A SKACH, W BROWN, D VANHOEK, AN MA, TH AF VERKMAN, AS SHI, LB FRIGERI, A HASEGAWA, H FARINAS, J MITRA, A SKACH, W BROWN, D VANHOEK, AN MA, TH TI STRUCTURE AND FUNCTION OF KIDNEY WATER CHANNELS SO KIDNEY INTERNATIONAL LA English DT Article ID CELL CHIP28 PROTEIN; RAT-KIDNEY; GLUCOSE TRANSPORTERS; COLLECTING TUBULE; XENOPUS OOCYTES; AQUAPORIN CHIP; MEMBRANE WATER; EXPRESSION; PERMEABILITY; LOCALIZATION AB There is now firm evidence that water transporting proteins are expressed in renal and extrarenal tissues. In the kidney, proximal-type (CHIP28) and collecting duct (WCH-CD) water channels have been identified. We have cloned three kidney cDNAs with homology to the water channel (aquaporin) family, including a mercurial-insensitive water channel (MIWC), and a glycerol-transporting protein (GLIP) in collecting duct basolateral membrane. To elucidate water transporting mechanisms, a series of molecular and spectroscopic studies were carried out on purified CHIP28 protein and expressed chimeric and mutated CHIP28 cDNAs. The results indicate that CHIP28 transports water selectively, that CHIP28 monomers are assembled in membranes as tetramers, but that individual monomers function independently. Monomers contain multiple membrane-spanning helical domains. Based on these data and recent electron crystallography results, a model for water transport is proposed in which water moves through narrow pores located within individual CHIP28 monomers. C1 UNIV CALIF SAN FRANCISCO, CARDIOVASC RES INST, DEPT PHYSIOL, SAN FRANCISCO, CA 94143 USA. MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02114 USA. SCRIPPS RES INST, LA JOLLA, CA USA. RP VERKMAN, AS (reprint author), UNIV CALIF SAN FRANCISCO, CARDIOVASC RES INST, DEPT MED, 1246 HLTH SCI E TOWER, SAN FRANCISCO, CA 94143 USA. RI Mitra, alok/P-7800-2016; OI Mitra, alok/0000-0003-0891-5697; Frigeri, Antonio/0000-0002-5284-2934 NR 68 TC 33 Z9 34 U1 1 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1995 VL 48 IS 4 BP 1069 EP 1081 DI 10.1038/ki.1995.390 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA RV926 UT WOS:A1995RV92600020 PM 8569068 ER PT J AU CARLBERG, KA GWOSDOW, AR ALVIN, BL AF CARLBERG, KA GWOSDOW, AR ALVIN, BL TI EFFECTS OF ANESTHESIA WITH HALOTHANE AND METHOXYFLURANE ON PLASMA-CORTICOSTERONE CONCENTRATION IN RATS AT REST AND AFTER EXERCISE SO LABORATORY ANIMAL SCIENCE LA English DT Article ID STRESS; INHIBITION; SECRETION; ENDOCRINE; HORMONE AB To determine whether halothane and methoxyflurane are suitable anesthetics for cardiac puncture in studies of plasma corticosterone concentration in rats, four experiments were done. Blood samples were taken immediately after rats became anesthetized with halothane or methoxyflurane. Decapitation without anesthesia was used to determine baseline corticosterone concentration. Another group of rats was anesthetized with ether as a positive control (known to stimulate corticosterone secretion). Corticosterone values in halothane- and methoxyflurane-treated rats were not significantly different from those measured after decapitation. Corticosterone concentration in halothane-treated rats was significantly lower than that in either methoxyflurane- or ether-treated rats. Cardiac puncture was done after 3 min of exposure to each of the three anesthetics. The results indicated that there were no differences in corticosterone values among the three anesthetics, suggesting that corticosterone concentration was lower immediately after halothane was used as the anesthetic, because halothane induced anesthesia in less time than that required for activation of adrenocortical secretion. To determine whether there was a difference among anesthetics in stimulating corticosterone secretion when anesthesia was maintained for a period before blood sample collection, cardiac puncture was done after 15 min of exposure to each of the three anesthetics. Corticosterone values were similar, suggesting that any of the three anesthetics was acceptable in this situation. To determine whether halothane or methoxyflurane affected exercise-induced increases in corticosterone values, exercise-trained rats were run for 30 min; then blood samples were collected by cardiac puncture immediately after induction of anesthesia with halothane, methoxyflurane, or ether, or after decapitation without anesthesia. Corticosterone values were not different among the three anesthetics or decapitation. C1 EASTERN WASHINGTON UNIV,DEPT MATH,CHENEY,WA 99004. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP CARLBERG, KA (reprint author), EASTERN WASHINGTON UNIV,DEPT BIOL,526 5TH ST,CHENEY,WA 99004, USA. FU NICHD NIH HHS [HD28228]; NIDDK NIH HHS [DK-41419] NR 20 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD OCT PY 1995 VL 45 IS 5 BP 584 EP 587 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA TB765 UT WOS:A1995TB76500021 PM 8569162 ER PT J AU DUTCHER, JP LEONG, T MAKARY, AZ BENNETT, J FRONTIERA, M MILLER, H WIERNIK, PH AF DUTCHER, JP LEONG, T MAKARY, AZ BENNETT, J FRONTIERA, M MILLER, H WIERNIK, PH TI A PHASE-II STUDY OF MENOGARIL (7R-O-METHYLNOGAROL) IN PATIENTS WITH RELAPSED/REFRACTORY ACUTE MYELOID-LEUKEMIA - A STUDY OF THE EASTERN-COOPERATIVE-ONCOLOGY-GROUP SO LEUKEMIA LA English DT Article DE LEUKEMIA; MENOGARIL; PHASE II AML; RELAPSE ID ANTHRACYCLINE; CELLS; 7-CON-O-METHYLNOGAROL; NOGALAMYCIN; MECHANISM; RESISTANT; ANALOGS; TUMORS; AGENT AB Fifty-one patients (47 evaluable) with AML, 27 in first relapse and 20 either in second relapse or refractory were treated with menogaril, 100 mg/m(2)/day as a 90-min infusion daily for 5 days. The complete response (CR) rate was 17% (8/47), and there was one partial response. Seven of eight responders were in first relapse with a 26% response rate among first relapse patients (7/27). The median duration of survival was 3 months for all first relapse patients and 4.3 months for all other patients. Toxicity included grades 3-4 pancytopenia and fever (100% of patients) and grades 3-4 stomatitis and hepatic enzyme elevation (25% of patients). Grades 3-4 cardiac toxicity occurred in three patients (two grade 3 arrhythmias and one heart block). All had previously received anthracyclines. Remission duration was 1.6-48+ months; two patients underwent bone marrow transplantation and continue in CR at 36+ and 48+ months. The nontransplanted patients remained in CR 1.6, 2.0, 3, 7, 14 and 27 months. Activity and toxicity of menogaril in this study were comparable to that of other clinically useful anthracyclines in AML. Further investigation of this agent in AML is warranted. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. GEISINGER MED CTR,MAYO CLIN,DANVILLE,PA 17822. UNIV ROCHESTER,ROCHESTER,NY. UNIV WISCONSIN,DEAN CLIN,MADISON,WI. NORTHWESTERN UNIV,EVANSTON COMMUNITY CANC,EVANSTON,IL. RP DUTCHER, JP (reprint author), MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,DEPT ONCOL,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [CA17145, CA13650, CA14958] NR 15 TC 7 Z9 7 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD OCT PY 1995 VL 9 IS 10 BP 1638 EP 1642 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA TA835 UT WOS:A1995TA83500005 PM 7564502 ER PT J AU MEINHARDT, G HASS, R AF MEINHARDT, G HASS, R TI DIFFERENTIAL EXPRESSION OF C-MYC, MAX AND MXI1 IN HUMAN MYELOID-LEUKEMIA CELLS DURING RETRODIFFERENTIATION AND CELL-DEATH SO LEUKEMIA RESEARCH LA English DT Article DE LEUKEMIA CELLS; DIFFERENTIATION; CELL CYCLE; C-MYC; RETRODIFFERENTIATION; CELL DEATH ID DNA-BINDING; REVERSIBLE INDUCTION; PROTEIN-SYNTHESIS; ACTIVATION; APOPTOSIS; ONCOGENE; CYCLE; GENES AB Previous studies in human myeloid leukemia cells (HL-60, U-937, THP-1) suggested an involvement of the c-myc gene in the control of mutually exclusive pathways, such as retrodifferentiation and cell death. Treatment of U-937 cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA) which is associated with the induction of a monocytic differentiation program and growth arrest, revealed an initial up-regulation of c-myc, c-max, and mxi1 mRNAs after 1-6 h. Thereafter, expression of these genes significantly declined to barely detectable levels when the cells ceased to grow after 12-24 h of TPA treatment. Between 7 and 11 days of TPA-induced G(0)/C-1 1 cell cycle arrest, expression of the c-max and mxi1 genes continuously increased up to 8-fold until 32 days and declined to control levels when the cells regained proliferative capacity by 36 days. In contrast, c-myc mRNAs remained down-regulated during periods of growth arrest and increased only during re-entry into the cell cycle after 36 days. This effect is consistent with a retrodifferentiation process, whereby previously differentiated cells revert back to the undifferentiated phenotype and re-enter the cell cycle. Different results were obtained during serum starvation-induced cell death of U-937 cells. After 48-72 h of serum starvation, expression of the c-myc and c-max genes were significantly down-regulated by 4-fold and 3-fold, respectively, while there was little, if any, change in mxi1 mRNA levels. Analysis of cell death in serum-starved U-937 cells demonstrated progressively increasing DNA fragmentation reaching 45.4% +/- 0.9% after 72 h. Synchronization of proliferating U-937 cells throughout distinct phases of the cell cycle exhibited little, if any, change in c-myc, c-max and mxi1 mRNAs. Furthermore, like c-myc, c-max and mxi1 mRNA transcripts appeared to be regulated primarily by post-transcriptional mechanisms, and c-max and mxi1 half-lives exceeded 4 h in contrast to <60 min for the c-myc gene. Taken together, these findings suggested differential regulation and inverse expression levels of c-myc compared to c-max and mxi1 during differentiation, retrodifferentiation and cell death. C1 INST PEPTIDFORSCH,D-30625 HANNOVER,GERMANY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. RI Hass, Ralf/F-3197-2012 OI Hass, Ralf/0000-0002-2481-7547 NR 32 TC 18 Z9 18 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD OCT PY 1995 VL 19 IS 10 BP 699 EP 705 DI 10.1016/0145-2126(95)00040-U PG 7 WC Oncology; Hematology SC Oncology; Hematology GA TJ747 UT WOS:A1995TJ74700003 PM 7500645 ER PT J AU SCHUMACHER, HR HOWE, HS AF SCHUMACHER, HR HOWE, HS TI SYNOVIAL-FLUID CELLS IN SYSTEMIC LUPUS-ERYTHEMATOSUS - LIGHT AND ELECTRON-MICROSCOPIC STUDIES SO LUPUS LA English DT Article DE SYNOVIAL FLUID ID HUMAN-LYMPHOCYTES; INTERFERON-ALPHA; TUBULAR ARRAYS; INCLUSIONS; CISTERNAE; TUMOR; SLE AB Joint fluid findings in systemic lupus erythematosus (SLE) have been described in only a few series and systematic electron microscopic study of the synovial fluid (SF) cells has not been reported. We describe the evaluation of 17 SF in patients with SLE with routine analysis and electron microscopy. Joint effusions had a wider range of leukocyte counts than often appreciated, with counts varying from 875 to 39 250 cells per mm(3). LE inclusions were seen in eight fluids and have been shown to contain chromatin-like filaments by electron microscopy. There was little associated electron dense immunoglobulin-like material. Tubuloreticular structures (TRS) found in seven SF were mostly in mononuclear cells including some LE cells. The known association of TRS with alpha interferon and viral infections may have important implications for pathogenesis. C1 TANTOK SENG HOSP,SINGAPORE,SINGAPORE. RP SCHUMACHER, HR (reprint author), VET AFFAIRS MED CTR,ARTHRIT UNIT,39TH & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 76 TC 3 Z9 4 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0961-2033 J9 LUPUS JI Lupus PD OCT PY 1995 VL 4 IS 5 BP 353 EP 364 DI 10.1177/096120339500400505 PG 12 WC Rheumatology SC Rheumatology GA TB729 UT WOS:A1995TB72900005 PM 8563729 ER PT J AU BOXERMAN, JL HAMBERG, LM ROSEN, BR WEISSKOFF, RM AF BOXERMAN, JL HAMBERG, LM ROSEN, BR WEISSKOFF, RM TI MR CONTRAST DUE TO INTRAVASCULAR MAGNETIC-SUSCEPTIBILITY PERTURBATIONS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MONTE CARLO MODELING; SUSCEPTIBILITY CONTRAST; CEREBRAL BLOOD VOLUME MAPPING; BLOOD OXYGENATION LEVEL-DEPENDENT CONTRAST ID BLOOD-VOLUME; HUMAN BRAIN; TRANSVERSE RELAXATION; SENSORY STIMULATION; CEREBRAL-ISCHEMIA; DIFFUSION; FLOW; OXYGENATION; CORTEX; WATER AB A particularly powerful paradigm for functional MR imaging of microvascular hemodynamics incorporates paramagnetic materials that create significant image contrast, These include exogenous (lanthanide chelates) and endogenous (deoxygenated hemoglobin) agents for mapping cerebral blood volume and neuronal activity, respectively, Accurate interpretation of these maps requires an understanding of the biophysics of susceptibility-based image contrast, The authors developed a novel Monte Carte model with which the authors quantified the relationship between microscopic tissue parameters, NMR imaging parameters, and susceptibility contrast in vivo. The authors found vascular permeability to water and the flow of erythrocytes to be relatively unimportant contributors to susceptibility-induced Delta R2. However, pulse sequence, echo time, and concentration of contrast agent have profound effects on the Vessel size dependence of Delta R2. For a model vasculature containing both capillaries and venules, the authors predicted a linear volume fraction dependence for physiological volume changes based on recruitment and dilation, and a concentration dependence that is nonlinear and pulse sequence dependent, Using the model, the authors demonstrated that spin echo functional images have greater microvascular sensitivity than gradient echo images, and that the specifics of the volume fraction and concentration dependence of transverse relaxivity change should allow for robust mapping of relative blood volume, The authors also demonstrated excellent agreement between the predictions of their model and experimental data obtained from the serial injection of superparamagnetic contrast agent in a rat model. C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,CAMBRIDGE,MA. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. RP BOXERMAN, JL (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR,BLDG 149 2301,13TH ST,BOSTON,MA 02129, USA. FU NHLBI NIH HHS [R01-HL39810]; PHS HHS [P01 48729] NR 35 TC 616 Z9 620 U1 1 U2 23 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD OCT PY 1995 VL 34 IS 4 BP 555 EP 566 DI 10.1002/mrm.1910340412 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RX751 UT WOS:A1995RX75100011 PM 8524024 ER PT J AU MCCARTHY, MJ SHROYER, AL SETHI, GK MORITZ, TE HENDERSON, WG GROVER, FL LONDON, MJ GIBBS, JO LANSKY, D MILLER, D CLARK, J HAMMERMEISTER, KE AF MCCARTHY, MJ SHROYER, AL SETHI, GK MORITZ, TE HENDERSON, WG GROVER, FL LONDON, MJ GIBBS, JO LANSKY, D MILLER, D CLARK, J HAMMERMEISTER, KE TI SELF-REPORT MEASURES FOR ASSESSING TREATMENT OUTCOMES IN CARDIAC-SURGERY PATIENTS SO MEDICAL CARE LA English DT Article DE HEALTH STATUS ASSESSMENT; CARDIAC SURGERY ID HEALTH SURVEY SF-36; FUNCTIONAL STATUS; VALIDITY; QUALITY; LIFE AB Patient self-report measures are increasingly valued as outcome variables in health services research studies. In this article, the authors describe the Functional Status, Health Related Quality of Life, Life Satisfaction, and Patient Satisfaction scales included in the Processes, Structures, and Outcomes of Cardiac Surgery (PSOCS) cooperative study underway within the Department of Veterans Affairs health care system. In addition to reporting on the baseline psychometric characteristics of these instruments, the authors compared preoperative Medical Outcomes Study SF-36 data from the study patients with survey data from a probability sample of the US population and with preoperative data on cardiac surgery patients from a high volume private sector surgical practice. Descriptive analyses indicate that the SF-36 profiles for all of the cardiac patients are highly similar. The Veterans Affairs and private sector patients report diminished physical functioning, physical role functioning, and emotional role functioning as well as reduced energy relative to an age-matched comparison sample. At the same time, however, the Veterans Affairs patients evidenced lower levels of capacity on most of the SF-36 dimensions relative to the private sector patients. C1 VET AFFAIRS MED CTR,DEPT HLTH SERV,DENVER,CO. VET AFFAIRS MED CTR,DEPT SURG SERV,DENVER,CO. VET AFFAIRS MED CTR,DEPT ANESTHESIOL,DENVER,CO. VET AFFAIRS MED CTR,DEPT CARDIOL,DENVER,CO. UNIV COLORADO,SCH MED,DENVER,CO. VET AFFAIRS MED CTR,DEPT CARDIOTHORAC SURG,TUCSON,AZ. UNIV ARIZONA,ARIZONA HLTH SCI CTR,TUCSON,AZ. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,COOPERAT STUDIES PROGRAM COORDINATING CTR,HINES,IL 60141. NORTHWESTERN UNIV,CTR HLTH SERV & POLICY RES,EVANSTON,IL 60208. UNIV ILLINOIS,SCH PUBL HLTH,EPIDEMIOL & BIOSTAT PROGRAM,CHICAGO,IL. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,CTR COOPERAT STUDIES HLTH SERV,HINES,IL 60141. PROVIDENCE HLTH SYST,CLIN INFORMAT SYST,PORTLAND,OR. VET AFFAIRS HOSP,HLTH SERV RES & DEV FIELD PROGRAM,BEDFORD,MA. RP MCCARTHY, MJ (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT PREVENT MED,SUITE 1102,680 LAKE SHORE DR,CHICAGO,IL 60611, USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 39 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 1995 VL 33 IS 10 SU S BP OS76 EP OS85 DI 10.1097/00005650-199510001-00009 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA TA873 UT WOS:A1995TA87300009 PM 7475415 ER PT J AU MORITZ, TE ELLIS, NK VILLANUEVA, CB STEEGER, JE LUDWIG, ST DEEGAN, NI SHROYER, AL HENDERSON, WG SETHI, GK GROVER, FL HAMMERMEISTER, KE AF MORITZ, TE ELLIS, NK VILLANUEVA, CB STEEGER, JE LUDWIG, ST DEEGAN, NI SHROYER, AL HENDERSON, WG SETHI, GK GROVER, FL HAMMERMEISTER, KE TI DEVELOPMENT OF AN INTERACTIVE DATA-BASE MANAGEMENT-SYSTEM FOR CAPTURING LARGE VOLUMES OF DATA SO MEDICAL CARE LA English DT Article DE DATA BASE MANAGEMENT; HIERARCHICAL DATA BASE; COMPUTER-ASSISTED INTERVIEW; DATA TRANSFER; DATA SECURITY AB Accurate collection and successful management of data are problems common to all scientific studies. For studies in which large quantities of data are collected by means of questionnaires and/or forms, data base management becomes quite laborious and time consuming. Data base management comprises data collection, data entry, data editing, and data base maintenance. In this article, the authors describe the development of an interactive data base management (IDM) system for the collection of more than 1,400 variables from a targeted population of 6,000 patients undergoing heart surgery requiring cardiopulmonary bypass. The goals of the IDM system are to increase the accuracy and efficiency with which this large amount of data is collected and processed, to reduce research nurse work load through automation of certain administrative and clerical activities, and to improve the process for implementing a uniform study protocol, standardized forms, and definitions across sites. C1 VET AFFAIRS MED CTR,CTR CONTINUOUS QUAL IMPROVEMENT,DENVER,CO. VET AFFAIRS MED CTR,RES DEPT,DENVER,CO. VET AFFAIRS MED CTR,DEPT HLTH SERV,DENVER,CO. VET AFFAIRS MED CTR,DEPT SURG SERV,DENVER,CO. VET AFFAIRS MED CTR,DEPT CARDIOL SERV,DENVER,CO. VET AFFAIRS MED CTR,BOSTON,MA. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV COLORADO,SCH MED,DENVER,CO. VET AFFAIRS MED CTR,DEPT CARDIOTHORAC SURG,TUCSON,AZ. UNIV ARIZONA,ARIZONA HLTH SCI CTR,TUCSON,AZ. RP MORITZ, TE (reprint author), US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,CTR COOPERAT STUDIES HLTH SERV,POB 5000,HINES,IL 60141, USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 9 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 1995 VL 33 IS 10 SU S BP OS102 EP OS106 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA TA873 UT WOS:A1995TA87300011 ER PT J AU VILLANUEVA, CB LUDWIG, ST SHROYER, AL DEEGAN, NI STEEGER, JE LONDON, MJ SETHI, GK GROVER, FL HAMMERMEISTER, KE AF VILLANUEVA, CB LUDWIG, ST SHROYER, AL DEEGAN, NI STEEGER, JE LONDON, MJ SETHI, GK GROVER, FL HAMMERMEISTER, KE TI VARIATIONS IN THE PROCESSES AND STRUCTURES OF CARDIAC-SURGERY NURSING-CARE SO MEDICAL CARE LA English DT Article DE NURSING EDUCATION; NURSING STRUCTURE; NURSING PROCESS; PATIENT CARE OUTCOMES; MULTIDISCIPLINARY TEAM AB Nurses play an invaluable role as key members of the cardiac surgery patient's medical care team. Over the last century, the nursing profession has become more independent and autonomous. Despite the widespread use of nursing quality indicators, the effect of nursing-specific processes and structures of care on patient outcomes is unknown. Thus, the Processes, Structures, and Outcomes of Care in Cardiac Surgery (PSOCS) study was initiated, in part, to determine the potential effect of nursing processes and structures of care on cardiac surgery patients' risk-adjusted outcomes. In this article, the authors summarize the key components of nursing structures of care incorporated in the PSOCS study. Nursing process variables were not sufficiently designed into the study to address hypotheses relating nursing care processes to patient outcomes. An analysis of the pilot test data from September 1992 to September 1993 demonstrated potentially important variations between the six pilot centers regarding nursing care provider profiles leg, educational preparation, specialty certification, and experience levels) and nursing staff ratios (eg, within the surgical intensive care unit). When linked to risk-adjusted patient outcomes, these variations in nursing structure of care may offer important insights toward improving the quality of care of cardiac surgery patients. C1 VET AFFAIRS MED CTR,DEPT HLTH SERV,DENVER,CO 80220. VET AFFAIRS MED CTR,DEPT ANESTHESIOL,DENVER,CO 80220. VET AFFAIRS MED CTR,DEPT SURG SERV,DENVER,CO 80220. VET AFFAIRS MED CTR,DEPT CARDIOL,DENVER,CO 80220. UNIV COLORADO,SCH MED,DENVER,CO. VET AFFAIRS MED CTR,PROC STRUCT & OUTCOMES CARE CARDIAC SURG STUDY,SAN ANTONIO,TX. VET AFFAIRS MED CTR,PROC STRUCT & OUTCOMES CARE CARDIAC SURG STUDY,BOSTON,MA. VET AFFAIRS MED CTR,TUCSON,AZ. UNIV ARIZONA,ARIZONA HLTH SCI CTR,TUCSON,AZ. RP VILLANUEVA, CB (reprint author), VET AFFAIRS MED CTR,PSOCS STUDY,1055 CLERMONT ST,DENVER,CO 80220, USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 13 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 1995 VL 33 IS 10 SU S BP OS59 EP OS65 DI 10.1097/00005650-199510001-00007 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA TA873 UT WOS:A1995TA87300007 PM 7475413 ER PT J AU CINCOTTA, AH MEIER, AH AF CINCOTTA, AH MEIER, AH TI BROMOCRIPTINE INHIBITS IN-VIVO FREE FATTY-ACID OXIDATION AND HEPATIC GLUCOSE OUTPUT IN SEASONALLY OBESE HAMSTERS (MESOCRICETUS-AURATUS) SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DEPENDENT DIABETES-MELLITUS; INSULIN RESISTANCE; SYRIAN-HAMSTERS; LIPOGENIC RESPONSIVENESS; PHOTOPERIODIC CONTROL; CIRCADIAN VARIATION; ENERGY-METABOLISM; PROLACTIN PERMITS; ADIPOSE-TISSUE; BODY-WEIGHT AB Seasonally obese hyperinsulinemic hamsters were treated for 5 weeks with bromocriptine (500 to 600 mu g per animal) and tested for drug effects on energy balance, body fat stores, nocturnal whole-body free fatty acid (FFA) metabolism and hepatic glucose output, and diurnal glucose tolerance. After 5 weeks, bromocriptine treatment reduced retroperitoneal fat pad weight by 45% without altering either daily food consumption or end-treatment total daily energy expenditure. Also, 5 weeks of treatment improved the diurnal glucose tolerance. resulting in a 47% and 33% decrease in the area under glucose and insulin curves, respectively. After 4 weeks, bromocriptine treatment reduced nocturnal lipolysis by 28%, palmitate rate of appearance into plasma by 30%, palmitate oxidation by 33%, and hepatic glucose output by 28%. Moreover, these reductions were accompanied by a 75% reduction in plasma insulin concentration. The data suggest that bromocriptine may improve diurnal glucose tolerance in part by inhibiting the preceding nocturnal lipolysis and FFA oxidation. Reductions in nocturnal FFA oxidation and hepatic glucose production may result from bromocriptine's influences on circadian organization of hypothalamic centers known to regulate these activities. Available evidence suggests that bromocriptine may impact this neuroendocrine organization of metabolism by increasing the dopamine to noradrenaline activity ratio in central (hypothalamic) and peripheral (eg, liver and adipose) target tissues. Copyright (C) 1995 by W.B. Saunders Company C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA. LOUISIANA STATE UNIV,DEPT ZOOL & PHYSIOL,BATON ROUGE,LA 70803. RP CINCOTTA, AH (reprint author), ERGO SCI INC,RES,100 1ST AVE,4TH FLOOR,BOSTON,MA 02129, USA. NR 70 TC 42 Z9 43 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 1995 VL 44 IS 10 BP 1349 EP 1355 DI 10.1016/0026-0495(95)90041-1 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TB960 UT WOS:A1995TB96000020 PM 7476296 ER PT J AU HIS, ED ZUKERBERG, LR SCHNITZER, B HARRIS, NL AF HIS, ED ZUKERBERG, LR SCHNITZER, B HARRIS, NL TI DEVELOPMENT OF EXTRASALIVARY GLAND LYMPHOMA IN MYOEPITHELIAL SIALADENITIS SO MODERN PATHOLOGY LA English DT Article DE NON-HODGKINS LYMPHOMA; MALTOMA; MYOEPITHELIAL SIALADENITIS; SJOGRENS SYNDROME; SALIVARY GLAND ID B-CELL LYMPHOMA; NON-HODGKINS LYMPHOMA; SJOGRENS-SYNDROME; MALIGNANT-LYMPHOMA; TISSUE LYMPHOMA; CD43 EXPRESSION; GRADE LYMPHOMA; DIFFERENTIATION; ACTIVATION; DIAGNOSIS AB Myoepithelial sialadenitis of the salivary gland is associated with an increased risk of lymphoma, but criteria that predict its development have not been clearly defined. We attempted to identify morphologic and immunologic features that correlated with the presence of extrasalivary lymphoma in patients with myoepithelial sialadenitis. Twenty-five patients (20 women, 5 men; median age, 56 yr) were studied with clinical follow-up in 22 patients; 19 were followed for 3 or more yr (median, 8.0 yr overall). Immunostains were done on paraffin sections in 28 of 31 specimens (22 of 25 patients) using antibodies to immunoglobulin Light chains, CD20, CD45RO, CD3, and CD43. Morphologic features studied included density of infiltrate, lymphoepithelial lesions, follicle atypia, and pattern of monocytoid B-cells. Twenty-four of 25 patients had dense lymphoid infiltrates expanding and effacing salivary gland architecture with lymphoepithelial lesions and epimyoepithelial islands; all but one of these cases showed monocytoid B-cells in and around ducts, whereas six also had interconnecting broad strands of these cells. One ease showed predominantly follicular hyperplasia. Two cases contained follicles with large atypical cells. Plasma cells were monotypic in four patients (18%) and polytypic in 18 (82%); in 18 of 28 specimens (64%) from 15 of 22 patients (68%), monocytoid B-cells coexpressed CD20 and CD43. Seven patients developed extrasalivary lymphoma, one before and six after the diagnosis of myoepithelial sialadenitis (median, 30.5 mo). Monotypic immunoglobulin in plasma cells correlated with past or subsequent extrasalivary lymphoma (P < 0.005); broad strands of monocytoid B-cells correlated with both monotypic plasma cells (P < 0.005) and extrasalivary lymphoma (P < 0.02). However, CD43 expression on monocytoid B-cells did not correlate with monotypic plasma cell immunoglobulin or extrasalivary lymphoma. Although the presence of monotypic plasma cell immunoglobulin correlated with extrasalivary lymphoma, lack of monotypic plasma cells in paraffin sections did not preclude its development. We conclude that the presence of broad, interconnecting strands of monocytoid B-cells is an important morphologic predictor of monoclonality and extrasalivary lymphoma in benign lymphoepithelial lesion/myoepithelial sialadenitis. CD43 expression on B-cells, in contrast, does not appear to increase the risk of the early development of extrasalivary lymphoma. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV MICHIGAN HOSP,DEPT PATHOL,ANN ARBOR,MI 48109. NR 26 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 1995 VL 8 IS 8 BP 817 EP 824 PG 8 WC Pathology SC Pathology GA TA395 UT WOS:A1995TA39500004 ER PT J AU XU, WH COOPER, GM AF XU, WH COOPER, GM TI IDENTIFICATION OF A CANDIDATE C-MOS REPRESSOR THAT RESTRICTS TRANSCRIPTION OF GERM CELL-SPECIFIC GENES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TESTIS-SPECIFIC EXPRESSION; PROTO-ONCOGENE PRODUCT; DEVELOPMENTAL REGULATION; MEIOTIC MATURATION; INITIATION SITE; XENOPUS OOCYTES; MOUSE-TISSUES; MEIOSIS-II; EGGS; RNA AB The c-mos proto-oncogene is specifically expressed in female and male germ cells. Previous studies identified a negative regulatory element (NRE) upstream of the c-mos promoter that suppresses c-mos transcription in transfected NIH 3T3 cells. In this study, we used gel shift assays to detect proteins in nuclear extracts of NIH 3T3 cells that bind to the c-mos NRE in a sequence-specific manner. One protein was found to bind to a region of the NRE which was shown by site-directed mutagenesis to be required for suppression of c-mos transcription. This factor was present in nuclear extracts of several somatic cell lines and tissues but not in male germ cells in which c-mos is transcribed, suggesting that it is a somatic cell repressor of c-mos transcription, The binding site of the candidate repressor within the c-mos NRE consists of sequences related to putative NREs identified in two other male germ cell-specific genes (encoding protamine 2 and phosphoglycerate kinase 2). The c-mos repressor bound and could be ITV cross-linked to these protamine 2 and phosphoglycerate kinase 2 gene sequences as a protein with an apparent molecular mass of similar to 30 kDa, The repressor binding site is also conserved in two other germ cell-specific genes (encoding testis-specific cytochrome c and heat shock-like protein 70), suggesting that the c-mos repressor may be generally involved in suppressing transcription of germ cell-specific genes in somatic cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NICHD NIH HHS [R01 HD26594] NR 31 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1995 VL 15 IS 10 BP 5369 EP 5375 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200019 PM 7565687 ER PT J AU ERHARDT, P TROPPMAIR, J RAPP, UR COOPER, GM AF ERHARDT, P TROPPMAIR, J RAPP, UR COOPER, GM TI DIFFERENTIAL REGULATION OF RAF-1 AND B-RAF AND RAS-DEPENDENT ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASE BY CYCLIC-AMP IN PC12 CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; COMPLETE CODING SEQUENCE; MAP KINASE; C-MOS; SIGNAL-TRANSDUCTION; XENOPUS-OOCYTES; MOUSE-TISSUES; IN-VITRO; ONCOGENE; CAMP AB Growth factor stimulation of the mitogen-activated protein (MAP) kinase pathway in fibroblasts is inhibited by cyclic AMP (cAMP) as a result of inhibition of Raf-1. In contrast, cAMP inhibits neither nerve growth factor-induced MAP kinase activation nor differentiation in PC12 pheochromocytoma cells, Instead, in PC12 cells cAMP activates MAP kinase. Since one of the major differences between the Ras/Raf/MAP kinase cascades of these cell types is the expression of B-Raf in PC12 cells, we compared the effects of cAMP on Raf-1 and B-Raf, In PC12 cells maintained in serum-containing medium, B-Raf was refractory to inhibition by cAMP, whereas Raf-1 was effectively inhibited, In contrast, both B-Raf and Raf-1 were inhibited by cAMP in serum-starved PC12 cells. The effect of cAMP is thus dependent upon growth conditions, with B-Raf being resistant to cAMP inhibition in the presence of serum. These results were extended by studies of Rat-1 fibroblasts into which B-Raf had been introduced by transfection. As in PC12 cells, B-Raf was resistant to inhibition by cAMP in the presence of serum, whereas Raf-1 was effectively inhibited, In addition, the expression of B-Raf rendered Rat-1 cells resistant to the inhibitory effects of cAMP on both growth factor-induced activation of MAP kinase and mitogenesis. These results indicate that Raf-1 and B-Raf are differentially sensitive to inhibition by cAMP and that B-Raf expression can contribute to cell type-specific differences in the regulation of the MAP kinase pathway. In contrast to the situation in PC12 cells, cAMP by itself did not stimulate MAP kinase in B-Raf-expressing Rat-1 cells. The activation of MAP kinase by cAMP in PC12 cells was inhibited by the expression of a dominant negative ras mutant, indicating that cAMP acts on a target upstream of Ras. Thus, it appears that a signaling component upstream of Ras is also required for cAMP stimulation of MAP kinase in PC12 cells. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV WURZBURG,ISNT MED RADIAT & CELL RES,WURZBURG,GERMANY. FU NCI NIH HHS [CA18689] NR 45 TC 118 Z9 118 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1995 VL 15 IS 10 BP 5524 EP 5530 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200036 PM 7565704 ER PT J AU BOUBNOV, NV WEAVER, DT AF BOUBNOV, NV WEAVER, DT TI SCID CELLS ARE DEFICIENT IN KU AND REPLICATION PROTEIN-A PHOSPHORYLATION BY THE DNA-DEPENDENT PROTEIN-KINASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STRAND BREAK REPAIR; COMBINED IMMUNE-DEFICIENCY; LYMPHOCYTE-B PRECURSORS; RNA POLYMERASE-II; V(D)J RECOMBINATION; IONIZING-RADIATION; ATAXIA-TELANGIECTASIA; RECEPTOR GENES; MICE; ENDS AB Cell mutants of the Ku nuclear DNA-binding complex are ionizing radiation sensitive and show V(D)J recombination defects. Ku binds and activates a catalytic subunit of DNA-dependent protein kinase (DNA-PK), although the substrates for DNA-PK are unknown. We found that scid cell extracts were deficient in Ku phosphorylation by DNA-PK. Human chromosome 8-complemented scid cells, containing the human DNA-PK catalytic subunit, restored Ku phosphorylation. Likewise, radiation-induced RPA hyperphosphorylation was not completed in scid cells compared,vith control or chromosome 8-reconstituted cells. Thus, the inactivity of DNA-PK is likely responsible for the repair and recombination defects in scid cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA54326] NR 67 TC 106 Z9 106 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1995 VL 15 IS 10 BP 5700 EP 5706 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200053 PM 7565721 ER PT J AU ZALVIDE, J DECAPRIO, JA AF ZALVIDE, J DECAPRIO, JA TI ROLE OF PRB-RELATED PROTEINS IN SIMIAN-VIRUS-40 LARGE-T-ANTIGEN-MEDIATED TRANSFORMATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SV40 LARGE-T; RETINOBLASTOMA SUSCEPTIBILITY GENE; ANCHORAGE-INDEPENDENT GROWTH; LARGE TUMOR-ANTIGEN; REGION 1A PROTEINS; CELL-CYCLE; TRANSCRIPTION FACTOR; GOVERNING SEQUENCE; BINDING PROTEIN; ADENOVIRUS E1A AB Simian virus 40 large T-antigen (TAg) transformation is thought to be mediated, at least in part, by binding to and modulating the function of certain cellular proteins, including the retinoblastoma tumor suppressor gene product, pRb, TAg can disrupt the inhibitory complexes formed by pRb with the oncogenic transcription factor E2F, and this mechanism has been suggested to be important for TAg-mediated transformation. Residues 102 to 114 of TAg (including the LXCXE motif) are required for binding to pRb. Mutations within this LXCXE motif abolish the ability of TAg to bind to pRb as well as to transform certain cell types. TAg can also bind to at least two other cellular proteins, p107 and p130, that are related to pRb by sequence homology and share the ability to bind E2F. However, whether p107 and p130 are also targets in TAg-mediated transformation is less clear. To assess the relative contribution of the inactivation of pRb, p107, and p130 to transformation by TAB, fibroblasts were prepared from embryos derived from matings of mice heterozygous for an Rb knockout allele. The ability of TAg to transform fibroblasts homozygous for either wild-type or knockout Rb alleles was evaluated. It is demonstrated that the integrity of the LXCXE motif provides a growth advantage in Rb+/+ and Rb-/- cells. Furthermore, wild-type TAg, but not the LXCXE mutants, could bind to p107 and p130 and disrupt p107-E2F and p130-E2F binding complexes. These results suggest that p107 and p130 participate in TAg-mediated transformation and that they may behave as tumor suppressors. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. OI Zalvide, Juan/0000-0001-7645-156X FU NCI NIH HHS [R01 CA63113] NR 63 TC 119 Z9 120 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1995 VL 15 IS 10 BP 5800 EP 5810 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200065 PM 7565733 ER PT J AU ESTOJAK, J BRENT, R GOLEMIS, EA AF ESTOJAK, J BRENT, R GOLEMIS, EA TI CORRELATION OF 2-HYBRID AFFINITY DATA WITH IN-VITRO MEASUREMENTS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST TRANSCRIPTIONAL ACTIVATORS; DNA-BINDING; C-MYC; PROTEIN PHOSPHATASE; SIGNAL TRANSDUCTION; MAX; GENE; REPRESSOR; TRANSFORMATION; DOMAINS AB Since their introduction, the interaction trap and other two-hybrid systems have been used to study protein-protein interactions, Despite their general use, little is known about the extent to which the degree of protein interaction determined by two-hybrid approaches parallels the degree of interaction determined by biochemical techniques, In this study, we used a set of lexAop-LEU2 and lexAop-lacZ reporters to calibrate the interaction trap, For the calibration, we used two sets of proteins, the Myc-Max-Mxi1 helix-leap-helix proteins, and wild-type and dimerization-defective versions of the lambda cI repressor, Our results indicate that the strength of interaction as predicted by the two-hybrid approach generally correlates with that determined in vitro, permitting discrimination of high-, intermediate-, and low-affinity interactions, but there was no single reporter for which the amount of gene expression linearly reflected affinity measured in vitro, However, some reporters showed thresholds and only responded to stronger interactions, Finally, some interactions were subject to directionality, and their apparent strength depended on the reporter used, Taken together, our results provide a cautionary framework for interpreting affinities from two-hybrid experiments. C1 FOX CHASE CANC CTR,INST CANC RES,PHILADELPHIA,PA 19111. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [R29 CA63366] NR 62 TC 409 Z9 419 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1995 VL 15 IS 10 BP 5820 EP 5829 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RV772 UT WOS:A1995RV77200067 PM 7565735 ER PT J AU RAPTIS, LH BROWNELL, HL LIU, SKW FIRTH, KL MACKENZIE, LW STILES, CD ALBERTA, JA AF RAPTIS, LH BROWNELL, HL LIU, SKW FIRTH, KL MACKENZIE, LW STILES, CD ALBERTA, JA TI APPLICATIONS OF ELECTROPORATION OF ADHERENT CELLS IN-SITU, ON A PARTLY CONDUCTIVE SLIDE SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE ELECTROPORATION; ADHERENT CELLS; INDIUM-TIN OXIDE; PEPTIDES; INTERCELLULAR COMMUNICATION; GAP JUNCTIONS ID NONPERMEANT MOLECULES; COMMUNICATION; ELECTROPERMEABILIZATION; TRANSFECTION; FIBROBLASTS; EXPRESSION; FUSION AB Nontraumatic, simple, and reproducible procedures for the introduction of nonpermeant molecules into adherent mammalian cells by in situ electroporation are described. Cells are grown on a glass slide, half of which is coated with electrically conductive, optically transparent, indium-tin oxide. An electric pulse is applied in the presence of the molecules to be introduced, and their effect on the cellular phenotype can be observed. The cells growing on the nonconductive side of the slide do not receive any pulse and serve as controls. Careful adjustment of electric field strength can achieve the introduction of the molecules into essentially 100% of the cells, and this treatment causes no detectable disruption to cellular metabolism. This is applied in the presence of the fluorescent dye, Lucifer yellow, causing its penetration into the cells growing on the conductive half of the slide. The migration of the dye to the nonelectroporated cells growing on the nonconductive area is microscopically observed under fluorescence illumination. C1 QUEENS UNIV,DEPT MICROBIOL & IMMUNOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT ANAT & CELL BIOL,KINGSTON,ON K7L 3N6,CANADA. ASK SCI PROD INC,KINGSTON,ON,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. NR 21 TC 10 Z9 10 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07012 SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD OCT PY 1995 VL 4 IS 2 BP 129 EP 138 DI 10.1007/BF02921607 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA TB318 UT WOS:A1995TB31800003 PM 8556428 ER PT J AU TOLENTINO, PJ DIKKES, P TSURUDA, L EBERT, K FINK, JS VILLAKOMAROFF, L LAMPERTI, ED AF TOLENTINO, PJ DIKKES, P TSURUDA, L EBERT, K FINK, JS VILLAKOMAROFF, L LAMPERTI, ED TI QUANTITATIVE-ANALYSIS OF THE EXPRESSION OF A VIP TRANSGENE SO MOLECULAR BRAIN RESEARCH LA English DT Article DE VASOACTIVE INTESTINAL POLYPEPTIDE; TRANSGENE; QUANTITATIVE PCR; CRYPTIC PROMOTER; LACZ ID VASOACTIVE-INTESTINAL-PEPTIDE; CYCLASE-ACTIVATING POLYPEPTIDE; NEURON-SPECIFIC EXPRESSION; POLYMERASE CHAIN-REACTION; RAT ANTERIOR-PITUITARY; MOLECULAR-CLONING; SUBSTANCE-P; FUNCTIONAL EXPRESSION; GENE-EXPRESSION; NEUROPEPTIDE-Y AB We have analyzed the expression of a transgene bearing 2 kilobases of the 5' flanking region of the human vasoactive intestinal polypeptide (VIP) gene coupled to beta-galactosidase. Expression was assayed by beta-galactosidase histochemistry and by mRNA quantitation using polymerase chain reaction (PCR)-mediated amplification; we compared beta-galactosidase activity against both transgene and endogenous VIP mRNA levels. We found that the human 5' flanking sequence in this construct is able to direct tissue-specific expression of beta-galactosidase similar to the pattern for endogenous VIP. However, the transgene is also expressed in smooth muscle and Schwann cells, where VIP mRNA is rare. In various tissues where the transgene and endogenous gene are both active, the ratio between their message levels differs dramatically - transgene mRNA is more abundant where VIP is relatively scarce, but is much less abundant than the endogenous message at sites where VIP mRNA is most concentrated. These results suggest that sequence elements that may restrict VIP transcription or cause tissue-specific VIP mRNA accumulation are missing from the transgene. In the testis there is a high level of transgene message but no significant beta-galactosidase activity; this discrepancy is caused by transcription from a cryptic promoter within the beta-galactosidase sequence. C1 CHILDRENS HOSP, DIV NEUROSCI, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02115 USA. TUFTS UNIV, SCH VET MED MED & DENT MED, DEPT ANAT & CELLULAR BIOL, GRAFTON, MA 01536 USA. MASSACHUSETTS GEN HOSP, MOLEC NEUROBIOL LAB, BOSTON, MA 02114 USA. FU NICHD NIH HHS [P30 HD18655]; NIGMS NIH HHS [T32 GM07753, T32 GM007753]; NINDS NIH HHS [R01 NS27832] NR 73 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT PY 1995 VL 33 IS 1 BP 47 EP 60 DI 10.1016/0169-328X(95)00105-2 PG 14 WC Neurosciences SC Neurosciences & Neurology GA RV140 UT WOS:A1995RV14000006 PM 8774945 ER PT J AU WEAVER, DR REPPERT, SM AF WEAVER, DR REPPERT, SM TI DEFINITION OF THE DEVELOPMENTAL TRANSITION FROM DOPAMINERGIC TO PHOTIC REGULATION OF C-FOS GENE-EXPRESSION IN THE RAT SUPRACHIASMATIC NUCLEUS SO MOLECULAR BRAIN RESEARCH LA English DT Article DE CIRCADIAN RHYTHM; IMMEDIATE EARLY GENE; ENTRAINMENT; LIGHT; SKF 38393; IN SITU HYBRIDIZATION ID PINEAL N-ACETYLTRANSFERASE; DEVELOPING CIRCADIAN SYSTEM; LIGHT; HAMSTER; BRAIN; IMMUNOREACTIVITY; SYNAPTOGENESIS; HYPOTHALAMUS; MELATONIN; NICOTINE AB D-1-dopamine receptor stimulation induces c-fos gene expression in the fetal suprachiasmatic nucleus (SCN), but not in the adult rat SCN. Light exposure at night induces c-fos gene expression in the adult SCN. The present experiments were designed to define the developmental transition from dopaminergic to photic regulation of c-fos gene expression in the SCN. Treatment with the D-1-dopamine receptor agonist SKF 38393 (10 mg/kg) increased SCN c-fos gene expression during both day and night on postnatal day (PD) 0, 1, and at night on PD 2, but the c-fos response disappeared by PD 4. Photic induction of c-fos gene expression was apparent during both day and night at each age examined, from PD 0 through PD 6. The magnitude and distribution of c-fos expression following light during the daytime was distinguishable from the response to light at night beginning on PD 2, indicating that the circadian clock regulates (gates) the c-fos response by PD 2. Orbital enucleation prevents the induction of c-fos by light at night on PD 2, indicating retinal mediation. Developmental loss of the c-fos response to SKF is not precipitated by the arrival of the retinohypothalamic tract; animals enucleated on PD 0 were insensitive to SKF on PD 6, as were visually intact controls. The results demonstrate that both dopaminergic and photic inputs can regulate SCN c-fos gene expression early in the neonatal period, and that the developmental loss of sensitivity to SKF is not due to the arrival of photic input to the SCN. The developmental transition from dopaminergic to photic regulation of c-fos gene expression roughly parallels the developmental transition from maternal to photic entrainment of the developing biological clock. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. RP WEAVER, DR (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS SERV,DEV CHRONOBIOL LAB,JACKSON 1226 GRJ 1226,BOSTON,MA 02114, USA. NR 40 TC 68 Z9 68 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT PY 1995 VL 33 IS 1 BP 136 EP 148 DI 10.1016/0169-328X(95)00117-B PG 13 WC Neurosciences SC Neurosciences & Neurology GA RV140 UT WOS:A1995RV14000016 ER PT J AU LEE, CW LUCK, MD JUPPNER, H POTTS, JT KRONENBERG, HM GARDELLA, TJ AF LEE, CW LUCK, MD JUPPNER, H POTTS, JT KRONENBERG, HM GARDELLA, TJ TI HOMOLOG-SCANNING MUTAGENESIS OF THE PARATHYROID-HORMONE (PTH) RECEPTOR REVEALS PTH-(1-34) BINDING DETERMINANTS IN THE 3RD EXTRACELLULAR LOOP SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TERNARY COMPLEX MODEL; EXPRESSION CLONING; MOLECULAR-CLONING; PLASMA-MEMBRANE; PEPTIDE; IDENTIFICATION; CAMP AB To identify determinants in the rat PTH receptor critical for binding the agonist peptide, PTH-(1-34), we systematically replaced 12 segments (5-33 residues) of the receptor's extracellular surface with the corresponding segments of the homologous rat secretin receptor and screened the resulting mutants in COS-7 cells for altered PTH-(1-34) binding properties. Surface expression of mutant receptors was assessed by the binding of monoclonal antibody 12CA5 to the epitope (HA)-tagged receptors. Of the nine well expressed and therefore informative receptor mutants, four bound radiolabeled PTH-(1-34) at levels that were proportional to the corresponding levels of surface expression, whereas five mutants bound [I-125]PTH-(1-34) to levels that were lower than predicted from the cell surface expression levels. These five mutations occurred at the extracellular (EC) end of transmembrane domain 1, the carboxy-terminal portion of the first EC loop, the second EC loop, and the third EC loop. We selected for further fine structure analysis the third EC loop; two specific residues, Trp-437 and Gin-440, were identified at which mutations caused 9- to 16-fold reductions in PTH-(1-34)-binding affinity. The same mutations had little or no effect on the binding affinity of PTH-(3-34). This study provides new information on the location of PTH receptor regions important for high affinity agonist binding and identifies two residues in the third extracellular loop which may contribute to interactions involving the hormone's critical amino terminus. C1 MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. NR 34 TC 78 Z9 78 U1 1 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1995 VL 9 IS 10 BP 1269 EP 1278 DI 10.1210/me.9.10.1269 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RY961 UT WOS:A1995RY96100001 PM 8544835 ER PT J AU ARAKI, E HAAG, BL MATSUDA, K SHICHIRI, M KAHN, CR AF ARAKI, E HAAG, BL MATSUDA, K SHICHIRI, M KAHN, CR TI CHARACTERIZATION AND REGULATION OF THE MOUSE INSULIN-RECEPTOR SUBSTRATE GENE PROMOTER SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ENHANCER-BINDING-PROTEIN; KINASE DOMAIN AUTOPHOSPHORYLATION; SIGNAL-TRANSDUCTION; GROWTH-FACTOR; GLUCOSE TRANSPORTER; 3T3-L1 ADIPOCYTES; MESSENGER-RNAS; BETA-ACTIN; EXPRESSION; REGION AB To evaluate the potential for regulation of the insulin receptor substrate IRS-1, we have cloned the mouse IRS-1 gene, identified its promoter, and analyzed promoter activity in the basal state and in response to stimulation. The 5'-region of the mouse IRS-1 gene lacks typical CAAT and TATA boxes but contains nine potential Spl binding sites consistent with a housekeeping gene. The 5'-region of the IRS-1 gene also has significant regions of homology with the promoters of the progesterone receptor gene, the insulin-like growth factor I receptor gene, and the androgen receptor gene. Multiple transcription start sites were identified 0.4-1.2 kilobases (kb) upstream from the start codon. Using a chloramphenicol acetyl transferase assay in Chinese hamster ovary (CHO) cells, basal promoter activity was present in the 3.2 kb 5'-flanking region of IRS-1 gene. Within this region, there were 184-base pair and 60-base pair negative regulatory elements at -3.2 kb and -1.6 kb surrounded by positive elements. By gel shift assay, a nuclear factor was identified in CHO cells which binds to -1606 and -1586 sequence in the negative regulatory element and appears to be distinct from C/EBP, CREB, and AP-1. In 3T3-F442A adipocytes dexamethasone treatment significantly decreased IRS-1 mRNA and IRS-1 protein. This was due to a decrease in the half-life of IRS-1 mRNA, with no change in IRS-1 promoter-chloramphenicol acetyl transferase activity. Insulin also decreased IRS-1 protein by similar to 60% within 9 h but did so without altering IRS-1 mRNA levels or chloramphenicol acetyl transferase activity. Thus, both insulin and dexamethasone down-regulate IRS-1 expression at the posttranscriptional level; with insulin this is probably due to an effect on protein half-life, whereas with dexamethasone the effect is due to a change in the half-life of IRS-1 mRNA. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED, JOSLIN DIABET CTR,DIV RES, BOSTON, MA 02115 USA. KUMAMOTO UNIV, SCH MED, DEPT METAB MED, KUMAMOTO 860, JAPAN. FU NIDDK NIH HHS [DK-36836, DK-33201] NR 56 TC 30 Z9 31 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD OCT PY 1995 VL 9 IS 10 BP 1367 EP 1379 DI 10.1210/me.9.10.1367 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RY961 UT WOS:A1995RY96100011 PM 8544845 ER PT J AU FORMAN, SA MILLER, KW YELLEN, G AF FORMAN, SA MILLER, KW YELLEN, G TI A DISCRETE SITE FOR GENERAL-ANESTHETICS ON A POSTSYNAPTIC RECEPTOR SO MOLECULAR PHARMACOLOGY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; LOCAL-ANESTHETICS; CHANNEL; MUTATIONS; CURRENTS; BINDING AB General anesthetics depress central nervous system excitability via a mechanism that probably involves effects on synaptic ion channels, but the fundamental molecular nature of the site where they act is unknown. Although the importance of hydrophobicity for general anesthetic drug potency has long been established, it remains uncertain whether these ''nonspecific'' drugs act on membrane proteins directly or by modification of the physical properties of the lipid membrane or the lipid-protein interface. We find that specific mutations in the acetylcholine receptor pore-forming M2 domains enhance the sensitivity of the receptor to the general anesthetics isoflurane, hexanol, and octanol, suggesting that these agents act by binding directly to a discrete protein site at or near these residues. The sensitivity of the receptor to block by general anesthetics increases with increased hydrophobicity of these residues, demonstrating that hydrophobic forces dominate the interaction of drugs with their protein site. Furthermore, octanol inhibits both wild-type and mutant nicotinic acetylcholine receptors preferentially after channel opening, which is consistent with a mechanism where drugs bind within the receptor's pore. Similar sites on postsynaptic ion channels in brain may represent general anesthetic targets for modulating consciousness. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114. OI Yellen, Gary/0000-0003-4228-7866 FU NIGMS NIH HHS [GM15904] NR 28 TC 142 Z9 145 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1995 VL 48 IS 4 BP 574 EP 581 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TA567 UT WOS:A1995TA56700002 PM 7476881 ER PT J AU CHEN, G WRIGHT, JE ROSOWSKY, A AF CHEN, G WRIGHT, JE ROSOWSKY, A TI DIHYDROFOLATE-REDUCTASE BINDING AND CELLULAR UPTAKE OF NONPOLYGLUTAMATABLE ANTIFOLATES - CORRELATES OF CYTOTOXICITY TOWARD METHOTREXATE-SENSITIVE AND METHOTREXATE-RESISTANT HUMAN HEAD AND NECK SQUAMOUS CARCINOMA-CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID BREAST CANCER-CELLS; CULTURED HUMAN HEAD; FOLYLPOLYGLUTAMATE SYNTHETASE; CROSS-RESISTANCE; CYTO-TOXICITY; TUMOR-CELLS; INVITRO; LINES; POLYGLUTAMATES; INHIBITION AB Several mechanisms have been demonstrated to be independently involved in methotrexate (MTX) resistance, including increased dihydrofolate reductase (DHFR) activity, decreased membrane transport, and decreased conversion to noneffluxing polyglutamates by folylpolyglutamate synthetase. We conducted the present study to test the hypothesis that nonpolyglutamatable antifolates with an N-delta-hemiphthaloyl-L-ornithine side chain could be more potent than MTX against MTX-sensitive and -resistant human carcinoma cells via tighter DHFR binding, more efficient cellular uptake, the ability to bypass defective polyglutamation, or a combination. Two nonpolyglutamatable antifolates, N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523) and the new B-ring analogue N-alpha-[4-[N-(2,4-diamino-5-chloroquinazolin-6-yl)methyl]amino] benzoyl-N-delta-hemiphthaloyl-L-ornithine (PT619), were tested as inhibitors of purified recombinant human DHFR and were found to bind somewhat better to the enzyme than MIX as determined by competitive radioligand binding assay. PT523 and PT619 were 9- and 14-fold, respectively, more active than MTX as inhibitors of parental SCC25 human and neck squamous carcinoma cell growth in 72-hr cultures. Moreover, there was an even greater increase in relative potency against two previously described MTX-resistant cell lines with an increased DHFR content and a decreased ability to convert MTX to polyglutamates: SCC25/R1 (selected with MTX) and SCC25/CP (selected with cisplatin but collaterally resistant to MTX). Both PT523 and PT619 very efficiently inhibited [H-3]MTX uptake by SCC25 cells in a 1-hr assay, with PT523 being Ii-fold more potent and PT619 being 17-fold more potent than MTX. Greater inhibition of [H-3]MIX uptake with PT523 and PT619 than with MTX was also observed in SCC25/R1 and SCC/CP cells. However, the increase in activity of PT523 and PT619 relative to MTX in uptake experiments was less than that in growth-inhibition assays, especially for SCC25/CP cells. This suggested that additional cytotoxicity determinants may exist in these resistant cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [R01-CA25394, P01-CA19589] NR 55 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1995 VL 48 IS 4 BP 758 EP 765 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TA567 UT WOS:A1995TA56700025 PM 7476904 ER PT J AU CHENG, TJ CHRISTIANI, DC WIENCKE, JK WAIN, JC XU, XP KELSEY, KT AF CHENG, TJ CHRISTIANI, DC WIENCKE, JK WAIN, JC XU, XP KELSEY, KT TI COMPARISON OF SISTER-CHROMATID EXCHANGE FREQUENCY IN PERIPHERAL LYMPHOCYTES IN LUNG-CANCER CASES AND CONTROLS SO MUTATION RESEARCH LETTERS LA English DT Article DE SCE; SISTER CHROMATID EXCHANGE (SCE); LUNG CANCER; CIGARETTE SMOKE; LYMPHOCYTE ID SMOKING; DNA; SUBSETS; SMOKERS; DAMAGE; SCE; MU AB Cytogenetic alterations have been associated with the occurrence of many cancers. However, limited data exist to address whether increased chromosomal changes in surrogate normal tissue are similarly associated with malignancy. As part of an ongoing case-control study of lung cancer, we have studied the factors that affect sister chromatid exchange (SCE) frequency in lymphocytes from lung cancer patients. Further, we sought to investigate whether the factors that affect SCE frequencies were comparable in lung cancer cases and controls. Cases had newly diagnosed, operable primary lung cancer. Controls were friends and spouses of cases. Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was obtained in an interviewer-administered questionnaire. Intake of antioxidants was also determined through the administration of a validated semiquantitative food frequency questionnaire. Metabolic traits studied included the polymorphic glutathione-S-transferase class mu (GST-mu) and variants of P450 isoenzymes CYP1A1 and CYP 2D6. Overall, 78 cases and 78 controls were included in the analysis. Although there was a small number of lung cancer patients who had never smoked in the study (9% of cases), these patients had higher SCE frequencies than current or former smokers. This suggests that factors associated with genomic instability may also play a role in the pathogenesis of lung cancer. The best fit model for SCE frequency, which had been previously generated from control data alone, included age, gender, smoking, GST-mu, and vitamin A intake. However, when this model was applied to lung cancer patients, smoking was not associated with an elevated SCE frequency. Thus, it is not clear that SCE frequency data in prevalent lung cancer cases and controls are comparable. C1 HARVARD UNIV, SCH PUBL HLTH, DEPT CANC BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT ENVIRONM HLTH, OCCUPAT HLTH PROGRAM, BOSTON, MA 02115 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, PULM & CRIT CARE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, THORAC SURG UNIT, BOSTON, MA 02114 USA. UNIV CALIF SAN FRANCISCO, DEPT EPIDEMIOL & BIOSTAT, MOLEC EPIDEMIOL LAB, SAN FRANCISCO, CA 94143 USA. RI Cheng, Tsun-Jen /D-3495-2012; Kelsey, Karl/I-1252-2014; OI CHENG, TSUN-JEN/0000-0002-2613-8230 FU NIEHS NIH HHS [ES/CA-06409, ES-00002] NR 23 TC 27 Z9 27 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-7992 J9 MUTAT RES LETT JI Mutat. Res. Lett. PD OCT PY 1995 VL 348 IS 2 BP 75 EP 82 DI 10.1016/0165-7992(95)00049-6 PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA TD980 UT WOS:A1995TD98000004 PM 7477055 ER PT J AU HORTON, TM GRAHAM, BH CORRALDEBRINSKI, M SHOFFNER, JM KAUFMAN, AE BEAL, MF WALLACE, DC AF HORTON, TM GRAHAM, BH CORRALDEBRINSKI, M SHOFFNER, JM KAUFMAN, AE BEAL, MF WALLACE, DC TI MARKED INCREASE IN MITOCHONDRIAL-DNA DELETION LEVELS IN THE CEREBRAL-CORTEX OF HUNTINGTONS-DISEASE PATIENTS SO NEUROLOGY LA English DT Article ID METABOLISM; BRAIN AB To determine if somatic mtDNA mutations might contribute to the neurodegeneration observed in con era Huntington's disease (HD), we quantitated the amount of the common mitochondrial 4977 nucleotide pair deletion (mtDNA(4977)) in cortex and putamen of HD patients and age-matched controls by the serial dilution-polymerase chain reaction method. Cortical deletion levels were analyzed in the temporal, frontal, and occipital lobes. HD temporal lobes had an Ii-fold greater mean mtDNA(4977) deletion level than age-matched controls, and HD frontal lobes had fivefold greater levels. HD occipital lobe and putamen deletion levels were comparable with control levels. These results support the hypothesis that HD is associated with elevated cortical mtDNA damage. C1 EMORY UNIV,SCH MED,DEPT GENET & MOLEC MED,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. OI Graham, Brett/0000-0001-8451-8154 FU NCRR NIH HHS [M01RR-00039]; NIA NIH HHS [1P30AG10130]; NINDS NIH HHS [NS21328] NR 20 TC 73 Z9 75 U1 1 U2 4 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1995 VL 45 IS 10 BP 1879 EP 1883 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA TA765 UT WOS:A1995TA76500016 PM 7477986 ER PT J AU HILL, RA CHIAPPA, KH HUANGHELLINGER, F JENKINS, BG AF HILL, RA CHIAPPA, KH HUANGHELLINGER, F JENKINS, BG TI EEG DURING MR-IMAGING - DIFFERENTIATION OF MOVEMENT ARTIFACT FROM PAROXYSMAL CORTICAL ACTIVITY SO NEUROLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP HILL, RA (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,EEG LAB,BIGELOW 12,FRUIT ST,BOSTON,MA 02114, USA. NR 2 TC 36 Z9 36 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1995 VL 45 IS 10 BP 1942 EP 1943 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA TA765 UT WOS:A1995TA76500032 PM 7478002 ER PT J AU BAUKROWITZ, T YELLEN, G AF BAUKROWITZ, T YELLEN, G TI MODULATION OF K+ CURRENT BY FREQUENCY AND EXTERNAL [K+] - A TALE OF 2 INACTIVATION MECHANISMS SO NEURON LA English DT Article ID HUMAN LYMPHOCYTES-T; POTASSIUM CHANNEL; MEMBRANE PATCHES; ASTROCYTES; BLOCKADE; SOMA AB Voltage-activated K+ currents and their inactivation properties are important for controlling frequency-dependent signaling in neurons and other excitable cells. Two distinct molecular mechanisms for K+ channel inactivation have been described: N-type, which involves rapid occlusion of the open channel by an intracellular tethered blocker, and C-type, which involves a slower change at the extracellular mouth of the pore. We find that frequency-dependent cumulative inactivation of Shaker channels is very sensitive to changes of extracellular [K+] in the physiological range, with much more inactivation at low [K+](out), and that it results from the interaction of N- and C-type inactivation. N-type inactivation enhances C-type inactivation by two mechanisms. First, it inhibits outward K+ flux, which normally fills an external ion site and thus prevents C-type inactivation. Second, it keeps the channel's activation gate open even after repolarization, allowing C-type inactivation to occur for a prolonged period. RP BAUKROWITZ, T (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02114, USA. OI Yellen, Gary/0000-0003-4228-7866 FU NINDS NIH HHS [NS29693, R01 NS029693] NR 31 TC 281 Z9 284 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD OCT PY 1995 VL 15 IS 4 BP 951 EP 960 DI 10.1016/0896-6273(95)90185-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA TC640 UT WOS:A1995TC64000023 PM 7576643 ER PT J AU PONTON, MO DARCOURT, J MILLER, BL CUMMINGS, JL SCHUMANN, SW MAEN, I AF PONTON, MO DARCOURT, J MILLER, BL CUMMINGS, JL SCHUMANN, SW MAEN, I TI PSYCHOMETRIC AND SPECT STUDIES IN ALZHEIMERS-DISEASE WITH AND WITHOUT DELUSIONS SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE ALZHEIMERS DISEASE; PSYCHOMETRIC MEASURE; SPECT; DELUSIONS ID CEREBRAL BLOOD-FLOW; EMISSION COMPUTED-TOMOGRAPHY; CAPGRAS SYNDROME; SINGLE-PHOTON; COGNITIVE PERFORMANCE; DEMENTIA; PERFUSION; BRAIN; MISIDENTIFICATION; HALLUCINATIONS AB Delusions are common in Alzheimer's disease (AD), but their pathophysiological basis is poorly understood. Fifteen patients meeting NINCDS-ADRDA criteria for probable AD were studied with psychometric assessment and brain-dedicated SPECT (xenon-133 and HMPAO). None of the subjects had delusions at the start of the study. One year later, psychometric testing and SPECT were repeated. Three patients had developed Capgras syndrome, and three others had developed non-Capgras delusional disorders in the interval. Psychometric and rCBF measures at baseline and at one year were compared. At baseline rCBF was significantly higher in the right temporal regions in the patients who developed delusions (p < 0.05). One year later, rCBF in the right temporal regions had declined in the psychotic patients. AD patients who developed delusions showed deterioration in right anterior temporal rCBF compared to AD without delusions. In the setting of AD, right temporal function deterioration may contribute to the development of delusions. C1 UNIV NICE,NICE,FRANCE. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. RP PONTON, MO (reprint author), UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT NEUROL,BLDG F9,1000 W CARSON ST,TORRANCE,CA 90509, USA. NR 63 TC 25 Z9 25 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD OCT PY 1995 VL 8 IS 4 BP 264 EP 270 PG 7 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA RZ144 UT WOS:A1995RZ14400004 ER PT J AU MENDEZ, MF VANGORP, W CUMMINGS, JL AF MENDEZ, MF VANGORP, W CUMMINGS, JL TI NEUROPSYCHIATRY, NEUROPSYCHOLOGY, AND BEHAVIORAL NEUROLOGY - A CRITICAL COMPARISON SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Note ID ALZHEIMERS-DISEASE; SCHIZOPHRENIA; DISORDERS; EPILEPSY; BRAIN; MOOD AB Neuropsychiatry, neuropsychology, and behavioral neurology share similar interests in brain-behavior disturbances. Recent advances in neuroscience have encouraged an increasing convergence of the three disciplines. These fields have differences in theoretical basis, professional and developmental background, most common brain-behavior focus, and principle clinical methods and therapies. This article compares neuropsychiatry, neuropsychology, and behavioral neurology and suggests how improved interdisciplinary knowledge and interactions can lead to greater understanding of the neurobiologic basis of behavior. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHOL SERV,LOS ANGELES,CA 90073. NR 40 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD OCT PY 1995 VL 8 IS 4 BP 297 EP 302 PG 6 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA RZ144 UT WOS:A1995RZ14400009 ER PT J AU POLLACK, AE FINK, JS AF POLLACK, AE FINK, JS TI ADENOSINE ANTAGONISTS POTENTIATE D-2 DOPAMINE-DEPENDENT ACTIVATION OF FOS IN THE STRIATOPALLIDAL PATHWAY SO NEUROSCIENCE LA English DT Article ID PREPROENKEPHALIN MESSENGER-RNA; RECEPTOR GENE-EXPRESSION; TERM RESERPINIZED MICE; IMMEDIATE-EARLY GENES; C-FOS; D2-DOPAMINE RECEPTORS; STRIATONIGRAL NEURONS; MOLECULAR-CLONING; UNILATERAL LESION; SELECTIVE LESION AB Adenosine antagonists potentiate dopamine-mediated behaviours. A(2a) adenosine and D-2 dopamine receptors are abundantly co-expressed within the striatopallidal subset of striatal neurons, suggesting that this is the site of interaction between A(2a) and D-2 receptors. We show that the D-2-dependent induction of the immediate early gene c-Fos occurs in striatopallidal neurons 3 h following injection of reserpine (10 mg/kg). We used this paradigm to test whether adenosine antagonists modulate D-2-dependent activation of striatopallidal neurons. The non-selective A1-A2 adenosine antagonists theophylline (25 mg/kg) or 3,7-dimethyl-1-propargylxanthine (25 mg/kg) potentiated the effect of a submaximal dose of the D-2 dopamine agonist quinpirole (0.05 mg/kg) to prevent the induction of striatal c-Fos following reserpine. Co-administration of the A(2a) receptor antagonist 8-(3-chlorostyryl) caffeine (5 mg/kg) with quinpirole (0.05 mg/kg) also attenuated striatal c-Fos induction following reserpine to a greater extent than 0.05 mg/kg quinpirole alone. When administered prior to reserpine, theophylline (25 mg/kg) or 3,7-dimethyl-1-propargylxanthine (25 mg/kg) partially attenuate the induction of striatal c-Fos. These results demonstrate that systemic administration of adenosine antagonists enhance D-2 dopamine receptor-dependent regulation of c-Fos in the striatopallidal pathway. These results support a functional interaction between A(2a) adenosine and D-2 dopamine receptors in striatopallidal neurons. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROBIOL LAB,BOSTON,MA 02114. FU NIDA NIH HHS [DA07496, T32-DA07282]; NINDS NIH HHS [NS31579] NR 46 TC 71 Z9 72 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT PY 1995 VL 68 IS 3 BP 721 EP 728 DI 10.1016/0306-4522(95)00168-I PG 8 WC Neurosciences SC Neurosciences & Neurology GA RQ723 UT WOS:A1995RQ72300008 PM 8577368 ER PT J AU SAYEGH, R SCHIFF, I WURTMAN, J SPIERS, P MCDERMOTT, J WURTMAN, R AF SAYEGH, R SCHIFF, I WURTMAN, J SPIERS, P MCDERMOTT, J WURTMAN, R TI THE EFFECT OF A CARBOHYDRATE-RICH BEVERAGE ON MOOD, APPETITE, AND COGNITIVE FUNCTION IN WOMEN WITH PREMENSTRUAL-SYNDROME SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID MENSTRUAL-CYCLE; FLUOXETINE; DEPRESSION; DISORDER; PROTEIN AB Objective: To test the efficacy of a specially-formulated, carbohydrate-rich beverage (one known to increase the serum ratio of tryptophan to other large neutral amino acids) on the mood, cognitive, and appetitive disturbances of premenstrual syndrome (FMS). Methods: Twenty-four women with confirmed PMS were enrolled in a double-blind, crossover study to test the efficacy of the specially-formulated beverage compared with two other isocaloric products on PMS symptoms. The study was conducted over three menstrual cycles preceded by a 1-month placebo run-in. Patients were tested at home or work using an interactive computer-telephone system. Standardized measurements of mood, cognitive performance, and food cravings were made before and 30, 90, and 180 minutes after consumption of active and placebo beverages during the late luteal phase of the menstrual cycle. Results: The experimental carbohydrate intervention significantly decreased self-reported depression, anger, confusion, and carbohydrate craving 90-180 minutes after intake. Memory word recognition was also improved significantly compared with scores obtained during the placebo run-in month (P < .05). The isocaloric placebo interventions had no significant effect on any of these measures. Conclusion: The results suggest that the psychological and appetitive symptoms of PMS can be relieved after consuming a specially-formulated, carbohydrate-rich beverage known to increase serum tryptophan levels. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. RP SAYEGH, R (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VINCENT MEM OBSTET & GYNECOL SERV,DIV REPROD ENDO,BOSTON,MA 02114, USA. NR 34 TC 87 Z9 87 U1 2 U2 5 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1995 VL 86 IS 4 BP 520 EP 528 DI 10.1016/0029-7844(95)00246-N PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RW226 UT WOS:A1995RW22600009 PM 7675373 ER PT J AU LANE, L TAMESIS, R RODRIGUEZ, A CHRISTEN, W AKOVA, YA MESSMER, E PEDROZASERES, M BARNEY, N FOSTER, CS AF LANE, L TAMESIS, R RODRIGUEZ, A CHRISTEN, W AKOVA, YA MESSMER, E PEDROZASERES, M BARNEY, N FOSTER, CS TI SYSTEMIC IMMUNOSUPPRESSIVE THERAPY AND THE OCCURRENCE OF MALIGNANCY IN PATIENTS WITH OCULAR INFLAMMATORY DISEASE SO OPHTHALMOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; LUPUS-ERYTHEMATOSUS; CANCER; CYCLOPHOSPHAMIDE; NEOPLASMS; AZATHIOPRINE; FOLLOW AB Purpose: To compare the occurrence of malignancy in patients with severe ocular inflammatory disease treated with systemic corticosteroids alone or with systemic immunosuppressive drugs with or without systemic corticosteroids. Methods: The clinical records of 543 patients with ocular inflammatory disease treated with systemic corticosteroids and/or immunosuppressive chemotherapy were reviewed in a retrospective cohort study. Characteristics of patients treated with corticosteroids alone were compared with characteristics of patients treated with immunosuppressive agents with or without preceding corticosteroid treatment. The rates of malignancy after initiation of drug therapy were compared using an exact test for incidence rate data. Results: Compared with patients treated with corticosteroids alone, patients treated with immunosuppressants with or without corticosteroid treatment were older and had more severe systemic disease. During a total of 1261 person-years of follow-up, a malignancy developed in five patients. The rate of malignancy in the immunosuppressant group (4 malignancies during 968 person-years of follow-up) was not significantly different from the rate in the corticosteroids alone group(1 malignancy during 293 person-years of follow-up) (P > 0.90, exact test for incidence rate data). Conclusion: These findings do not support the hypothesis of an increased risk of malignancy in patients with severe ocular inflammatory disease who are treated with systemic immunosuppressive agents compared with patients treated with systemic corticosteroids. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. UNIV NEBRASKA,MED CTR,DEPT OPHTHALMOL,OMAHA,NE. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV PREVENT MED,BOSTON,MA 02115. NR 39 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 1995 VL 102 IS 10 BP 1530 EP 1535 PG 6 WC Ophthalmology SC Ophthalmology GA RZ487 UT WOS:A1995RZ48700026 PM 9097802 ER PT J AU JAINKITTIVONG, A YEH, CK GUEST, GF COTTONE, JA AF JAINKITTIVONG, A YEH, CK GUEST, GF COTTONE, JA TI EVALUATION OF MEDICAL CONSULTATIONS IN A PREDOCTORAL DENTAL CLINIC SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article AB Objective. A patient's medical condition can affect the delivery of dental care. Medical consultation is indicated for dental patients whose medical history is uncertain or when physical assessment may indicate an untreated medical problem. The aims of this study were to evaluate the use of medical consultation and determine how it affects dental treatment plans in a predoctoral dental clinic program. Study design. Reviews of 147 medical consultation requests were performed. Results. The main reasons for medical consultations were cardiovascular assessment (51.5%) and diabetic status determination (12.6%). In the cardiovascular assessment category, hypertension (48.1%) and heart murmur (17.9%) were primary concerns. Main dental concerns were the need for preoperative antibiotic prophylaxis (33.3%) and the use of vasoconstrictors (20.4%). Overall, 32.1% of medical consultations resulted in an alteration in dental treatment plans. As a result of medical consultations, 8% commenced their medical management. Conclusions. These results indicated that medical consultations could reduce the medical risk associated with dental procedures and unnecessary antibiotic prophylaxis. Therefore for many dental patients, good communication between dentists and physicians is essential for adequate care. C1 UNIV TEXAS,HLTH SCI CTR,SCH DENT,DEPT DENT DIAGNOST SCI,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. NR 9 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD OCT PY 1995 VL 80 IS 4 BP 409 EP 413 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TA766 UT WOS:A1995TA76600012 PM 8521104 ER PT J AU GULLEY, ML SARGEANT, KP GRIDER, DJ EAGAN, PA DAVEY, DD DAMM, DD ROBINSON, RA VANDERSTEEN, DP MCGUFF, S BANKS, PM AF GULLEY, ML SARGEANT, KP GRIDER, DJ EAGAN, PA DAVEY, DD DAMM, DD ROBINSON, RA VANDERSTEEN, DP MCGUFF, S BANKS, PM TI LYMPHOMAS OF THE ORAL SOFT-TISSUES ARE NOT PREFERENTIALLY ASSOCIATED WITH LATENT OR REPLICATIVE EPSTEIN-BARR-VIRUS SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID NON-HODGKINS-LYMPHOMAS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; T-CELL LYMPHOMAS; MORPHOLOGICAL SUBDIVISION; CLINICAL-SIGNIFICANCE; GENE-EXPRESSION; DNA; LEUKOPLAKIA; DISEASE; RNAS AB Objectives. Epstein-Barr virus is periodically shed in the saliva of persons infected by the virus.Epstein-Barr virus has been implicated in the pathogenesis of certain subtypes of lymphoma, particularly high-grade lymphomas. Because high-grade subtypes represent the majority of lymphomas that arise in oral soft tissues, we hypothesized that Epstein-Barr virus might be preferentially associated with oral lymphomas. Study Design, A series of 34 oral lymphomas were diagnosed according to the revised European-American classification scheme. They were examined for the presence of latent Epstein-Barr virus by EBER1 in situ hybridization and for expression of the Epstein-Barr virus replicative protein, BZLF1, by immunohistochemistry. Results, Epstein-Barr virus EBER1 transcripts were detected in 11 of 31 oral lymphomas including 7 of 10 AIDS-related lymphomas and only 4 of 21 lymphomas that occurred in nonimmunocompromised persons. The Epstein-Barr virus-containing lymphomas were art high-grade histologic subtypes, that is, diffuse large cell, immunoblastic, or Burkitt's lymphomas. In contrast, Epstein-Barr virus was not detected in any of five tow-grade oral lymphomas. in the single case of T-cell lymphoma in this study, EBER1 was expressed in the tumor cells. A switch from viral latency to replication, as measured by EBV BZLF1 expression, was identified in rare lymphoma cells in only four cases. This rate of viral replication was not higher than what has been reported in lymphomas arising at other anatomic sites. Although one of our lymphomas arose at a site oi previous oral hairy leukoplakia, there was no other evidence that Epstein-Barr virus replication predisposed to development or persistence of oral lymphomas. Conclusions. These data suggest that even though Epstein-Barr virus is frequently found in oral secretions, neither latent nor replicative Epstein-Barr virus is present more commonly in oral lymphomas than in lymphomas arising in other anatomic sites, when controlling for immunodeficiency status. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. BROOKE ARMY MED CTR,FT SAM HOUSTON,TX 78234. UNIV KENTUCKY,MED CTR,LEXINGTON,KY 40506. UNIV IOWA HOSP & CLIN,IOWA CITY,IA 52242. WILFORD HALL USAF MED CTR,LACKLAND AFB,TX. RP GULLEY, ML (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NCI NIH HHS [K08-CA01615] NR 35 TC 15 Z9 15 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD OCT PY 1995 VL 80 IS 4 BP 425 EP 431 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TA766 UT WOS:A1995TA76600015 PM 8521106 ER PT J AU POREMBA, C YANDELL, DW MELLIN, W SCHMID, KW REERS, B BOCKER, W DOCKHORNDWORNICZAK, B AF POREMBA, C YANDELL, DW MELLIN, W SCHMID, KW REERS, B BOCKER, W DOCKHORNDWORNICZAK, B TI ADENOCARCINOMA OF THE CARDIA IN A YOUNG MAN - DETECTION OF SOMATIC P53 MUTATION BY IMMUNOHISTOCHEMISTRY AND AUTOMATED DIRECT SEQUENCING SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE GASTRIC CANCER; P53 TUMOR-SUPPRESSOR GENE; PROGNOSTIC MARKER; IMMUNOHISTOCHEMISTRY; AUTOMATED DIRECT SEQUENCING ID GASTRIC-CARCINOMA; COLORECTAL-CARCINOMA; CANCER; OVEREXPRESSION; EXPRESSION; GENE AB we describe the unusual case of early-onset adenocarcinoma of the cardia in a 22-year-old male. The patient died within less than one year after diagnosis was established. By immunohistochemistry, p53 expression was observed in the tumor cells. Automated direct sequencing of polymerase chain reaction (PCR) amplified DNA revealed a homozygous transition in p53 codon 280 (AGA to GGA) as the molecular basis of p53 accumulation. Previous studies suggest that gastric carcinomas with mutations in the p53 tumor-suppressor gene are associated with particularly poor prognosis when compared with tumors without p53 mutations. Since carriers of p53 mutations in the germline have a 50 percent likelihood of developing cancer before the age of 30, we examined tumor-free tissue for the presence of a germline mutation in codon 280, but none was found. C1 UNIV MUNSTER,GERHARD DOMAGK INST PATHOL,D-48149 MUNSTER,GERMANY. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HOWE LAB MOLEC GENET,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV VERMONT,DEPT PATHOL,BURLINGTON,VT 05405. OTTO VONGUERICKE UNIV,DEPT PATHOL,MAGDEBURG,GERMANY. UNIV MUNSTER,DEPT SURG,W-4400 MUNSTER,GERMANY. NR 21 TC 3 Z9 3 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49 POSTFACH 72 01 43, D-70577 STUTTGART, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PD OCT PY 1995 VL 191 IS 10 BP 1004 EP 1009 PG 6 WC Pathology SC Pathology GA TJ951 UT WOS:A1995TJ95100007 PM 8838368 ER PT J AU INGELFINGER, JR AF INGELFINGER, JR TI ASK THE EXPERT SO PEDIATRIC NEPHROLOGY LA English DT Article DE ESSENTIAL HYPERTENSION; TREATMENT RP INGELFINGER, JR (reprint author), MASSACHUSETTS GEN HOSP,DIV PEDIAT NEPHROL,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD OCT PY 1995 VL 9 IS 5 BP 552 EP 552 PG 1 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA TB872 UT WOS:A1995TB87200004 PM 8580007 ER PT J AU GAHL, WA INGELFINGER, J MOHAN, P BERNARDINI, I HYMAN, PE TANGERMAN, A AF GAHL, WA INGELFINGER, J MOHAN, P BERNARDINI, I HYMAN, PE TANGERMAN, A TI INTRAVENOUS CYSTEAMINE THERAPY FOR NEPHROPATHIC CYSTINOSIS SO PEDIATRIC RESEARCH LA English DT Article ID VOLATILE SULFUR-COMPOUNDS; GAS-CHROMATOGRAPHY; CHILDREN; INSUFFICIENCY; METHIONINE; TRANSPORT; FRACTIONS; PATIENT; PROTEIN; ADULT AB A 4-y-old boy with nephropathic cystinosis and gastrointestinal dysmotility of unknown etiology was treated with i.v. cysteamine over a period of 10 mo. Thirty minutes after a dose of 10 mg/kg cysteamine free base, the leukocyte cystine value had fallen from 11.9 to 4.9 nmol of half-cystine/mg of protein. When cysteamine was given every 6 h, the leukocyte cystine concentration, measured 5-7 h after a dose, decreased with increasing cysteamine doses up to 17 mg/kg; at this dose the cystine value was 1.1 nmol of half-cystine/mg of protein, or 9% of the untreated value. Oral administration of approximately 16 mg/kg per dose every 6 h to this patient over the previous 3 y achieved similar leukocyte cystine depletion, to 1.2 nmol of half-cystine/mg of protein. The plasma cysteamine concentration 30 min after a dose of 10 mg/kg was 71 mu M; 5-7 after a dose of up to 20 mg/kg, the concentration was below 5 mu M. Dimethylsulfide was elevated in the breath and urine of this boy after, but not before, the initiation of i.v. cysteamine therapy. Ten months after the start of therapy, the patient tolerated 250 mg (14 mg/kg) every 8 h. Adverse effects of this treatment included lethargy and increased nausea and vomiting when a schedule of therapy every 6 h was attempted. This investigation demonstrates that cysteamine given through a central venous catheter is effective in reducing leukocyte cystine levels. C1 CHILDRENS NATL MED CTR,DIV GASTROENTEROL & NUTR,WASHINGTON,DC 20010. CHILDRENS HOSP ORANGE CTY,DEPT PEDIAT GASTROENTEROL,ORANGE,CA 92668. UNIV NIJMEGEN HOSP,DIV GASTROINTESTINAL & LIVER DIS,6500 HB NIJMEGEN,NETHERLANDS. MASSACHUSETTS GEN HOSP,DEPT NEPHROL,BOSTON,MA 02115. RP GAHL, WA (reprint author), NICHHD,HUMAN BIOCHEM GENET SECT,BLDG 10,ROOM 9S-242,BETHESDA,MD 20892, USA. NR 41 TC 16 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD OCT PY 1995 VL 38 IS 4 BP 579 EP 584 DI 10.1203/00006450-199510000-00018 PG 6 WC Pediatrics SC Pediatrics GA RV971 UT WOS:A1995RV97100018 PM 8559613 ER PT J AU ROSENTHAL, DI DOPPELT, SH MANKIN, HJ DAMBROSIA, JM XAVIER, RJ MCKUSICK, KA ROSEN, BR BAKER, J NIKLASON, LT HILL, SC MILLER, SPF BRADY, RO BARTON, NW AF ROSENTHAL, DI DOPPELT, SH MANKIN, HJ DAMBROSIA, JM XAVIER, RJ MCKUSICK, KA ROSEN, BR BAKER, J NIKLASON, LT HILL, SC MILLER, SPF BRADY, RO BARTON, NW TI ENZYME REPLACEMENT THERAPY FOR GAUCHER DISEASE - SKELETAL RESPONSES TO MACROPHAGE-TARGETED GLUCOCEREBROSIDASE SO PEDIATRICS LA English DT Article DE GAUCHER DISEASE; ENZYME REPLACEMENT THERAPY; MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; BONE MARROW; COMBINED CORTICAL THICKNESS; TRABECULAR BONE DENSITY ID BONE-MARROW; CELLS; OSTEOPOROSIS; DEFICIENCY; PATIENT; WOMEN; CT AB Objectives. Reversal of the hematologic and Visceral abnormalities characteristic of Gaucher disease, the most common lipid storage disorder, with biweekly infusions of macrophage-targeted glucocerebrosidase (glucosylceramidase) is well documented. The extent to which the skeleton responds to enzyme replacement therapy has not been systematically investigated. Methods. To assess the skeletal response to enzyme replacement therapy, we treated 12 patients with type 1 Gaucher disease, who had intact spleens, with macrophage-targeted glucocerebrosidase. The initial dose of enzyme was 60 U/kg body weight every 2 weeks for 24 months, followed by reduction in dosage to 30 and then 15 U/kg body weight every 2 weeks, each for 9 months. Results. The lipid composition of bone marrow, determined by direct chemical analysis, began to improve after 6 months of treatment at a time when noninvasive imaging studies showed no significant changes. By 42 months, improvement in marrow composition was demonstrable on all noninvasive, quantitative imaging modalities (magnetic resonance score, quantitative xenon scintigraphy, and quantitative chemical shift imaging) used in this study. Quantitative chemical shift imaging, the most sensitive technique, demonstrated a dramatic normalization of the marrow fat content in all patients. Net increases in either cortical or trabecular bone mass, as assessed by combined cortical thickness measurements and dual-energy quantitative computed tomography, respectively, occurred in 10 patients. Conclusions. Prolonged treatment over 31/2 years with macrophage-targeted glucocerebrosidase produces objective reversal of disease in both the axial and appendicular skeleton in patients with Gaucher disease. Marked mass in both children and adults. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. RP ROSENTHAL, DI (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,WHITE 289,BOSTON,MA 02114, USA. NR 48 TC 154 Z9 158 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 1995 VL 96 IS 4 BP 629 EP 637 PN 1 PG 9 WC Pediatrics SC Pediatrics GA RY677 UT WOS:A1995RY67700005 PM 7567322 ER PT J AU NETSCHER, DT PATRINELY, JR PELTIER, M POLSEN, C THORNBY, J AF NETSCHER, DT PATRINELY, JR PELTIER, M POLSEN, C THORNBY, J TI TRANSCONJUNCTIVAL VERSUS TRANSCUTANEOUS LOWER EYELID BLEPHAROPLASTY - A PROSPECTIVE-STUDY SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LOWER-LID BLEPHAROPLASTY; ORBITAL FRACTURES; INCISIONS AB Debate continues over the relative merits of transconjunctival and the more customary subciliary transcutaneous approaches for lower lid blepharoplasty. Tell consecutive patients presented for blepharoplasty, and in all patients the transcutaneous subciliary musculocutaneous flap approach was used on the left lower eyelid and the transconjunctival preseptal approach was used on the right. Patients served as their own controls. Followup was evaluated clinically by patient questionnaire and by standardized photographs preoperatively and at 5 days, 1 month, 3 months, and 6 months postoperatively. Photographs were graded independently by four blinded examiners. No statistical difference was identified in measured fornix depth between preoperative patients and postoperatively on each side. Average fat removed from each side was the same, and no patient had an identified ''missed fat compartment.'' Three patients had mild bilateral scleral show postoperatively, and a fourth developed it on the left (transcutaneous) side. However, overall grading on both sides was universally very good with no significant difference on the two sides-0.68 on the right and 0.60 on the left (maximum worst grade could be 5.0 and best grade 0). The potential for external scarring was never a perceived problem in the transcutaneous technique. C1 DEPT VET AFFAIRS MED CTR,PLAST SURG SERV,HOUSTON,TX. BAYLOR COLL MED,DIV PLAST SURG,HOUSTON,TX 77030. NR 22 TC 26 Z9 26 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 1995 VL 96 IS 5 BP 1053 EP 1060 DI 10.1097/00006534-199510000-00007 PG 8 WC Surgery SC Surgery GA RX593 UT WOS:A1995RX59300007 PM 7568479 ER PT J AU NETSCHER, DT WEIZER, G WIGODA, P WALKER, LE THORNBY, J BOWEN, D AF NETSCHER, DT WEIZER, G WIGODA, P WALKER, LE THORNBY, J BOWEN, D TI CLINICAL RELEVANCE OF POSITIVE BREAST PERIPROSTHETIC CULTURES WITHOUT OVERT INFECTION SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID CAPSULAR CONTRACTURE; IMPLANTS; COLONIZATION AB The true incidence of positive breast periprosthetic cultures in the absence of overt infection is not clearly established. We retrospectively reviewed data fr om 389 implants that were removed for reasons other than clinical infection. Many of these patients presented with a variety of musculoskeletal ailments. Others had symptomatic capsular contracture as the presenting complaint In a few a known implant rupture was the reason for explantation. We identified a positive culture rate of 23.5 percent from capsule tissue. Most of these organisms were coagulase-negative staphylococci and anaerobic diphtheroids, but fungi and other organisms (generally felt to be more pathogenic than the less virulent coagulase-negative staphylococci) also were cultured. In an attempt to identify the clinical relevance of these positive cultures, we statistically evaluated the culture results for associations with capsular contracture, implant rupture, type of implant, and location of implant. Of these, the only statistically significant correlation was between positive culture result and symptomatic capsular contracture (Baker class IV). C1 BAYLOR COLL MED,DIV PLAST SURG,HOUSTON,TX 77030. UNIV TEXAS,SW MED CTR,DEPT SURG,DALLAS,TX 75235. DEPT VET AFFAIRS MED CTR,HOUSTON,TX. NR 25 TC 56 Z9 56 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 1995 VL 96 IS 5 BP 1125 EP 1129 DI 10.1097/00006534-199510000-00020 PG 5 WC Surgery SC Surgery GA RX593 UT WOS:A1995RX59300020 PM 7568489 ER PT J AU CHOI, M RABB, H ARNAOUT, MA EHRLICH, HP AF CHOI, M RABB, H ARNAOUT, MA EHRLICH, HP TI PREVENTING THE INFILTRATION OF LEUKOCYTES BY MONOCLONAL-ANTIBODY BLOCKS THE DEVELOPMENT OF PROGRESSIVE ISCHEMIA IN RAT BURNS SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID THERMAL-INJURY; INFLAMMATORY RESPONSE; ADHERENCE; COMPLEMENT; MOLECULE; SKIN; CD18 AB Tissue loss as a consequence of thermal trauma occurs in two stages. There is immediate necrosis in tissues directly killed by the thermal energy, followed by a delayed secondary necrosis in neighboring tissues. The infiltration of neutrophils into traumatized tissues is a hallmark of the inflammatory response. Neutrophils have the machinery to kill invading microorganisms, but these same weapons have the capacity to destroy the host's viable tissues as well. Leukocyte infiltration requires their adherence to the vascular endothelial cell surface. Masking these adhesion sites on neutrophils will block the adhesion of neutrophils to the endothelium. A monoclonal antibody (mAb) was developed to guinea pig leukocyte adhesion sites CD11b/CD18, and this mAb cross-reacts with rat leukocytes, blocking their adherence. Rats received a ''comb burn'' composed of four rectangular full-thickness burns placed in a row and separated by three areas left unburned. The four individual burns convert into a single large wound because the blood flow to the interspaces was terminated, blood vessels were occluded, and leukocytes were present in the extravascular space. The systemic administration of the mAb (50 to 150 mu l) immediately following a comb burn promoted the survival of the interspace, demonstrated by the prevention of loss of blood flow by laser Doppler monitoring, maintained patent vessels by latex vascular casts, blocked extravascular migration of neutrophils histologically at 2 hours, and limited the tissue loss to the original four burns. C1 MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,RENAL UNIT,WOUND HEALING LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIAID NIH HHS [AI 21964]; NIDDK NIH HHS [DK 48549]; NIGMS NIH HHS [GM 32705] NR 28 TC 34 Z9 34 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 1995 VL 96 IS 5 BP 1177 EP 1185 DI 10.1097/00006534-199510000-00027 PG 9 WC Surgery SC Surgery GA RX593 UT WOS:A1995RX59300027 PM 7568496 ER PT J AU TYAN, ML AF TYAN, ML TI EFFECTS OF VITAMIN-A AND INOSITOL ON TERM WEIGHTS OF H-2 CONGENIC MICE SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID PLACENTAL-LACTOGEN RELEASE; HUMAN TROPHOBLASTIC CELLS; PHOSPHATE PRODUCTION; GROWTH; METABOLISM; ENDOCRINE; FETUS AB Pregnant H-2 congenic mice, C57BL/10, B10.A, B10.A(15R), and B10.A(18R) were fed Purina Laboratory Chow 5001 or the same diet supplemented with 400 IU vitamin A dissolved in corn oil or 0.4% (w/w) myo-inositol, On the 18th day of gestation, the dams were sacrificed, and the fetuses were weighed, sexed, and examined for developmental abnormalities. Term fetal weight was found to be significantly reduced in progeny of darns bearing d alleles distal to Ea in the H-2 complex when the diet was supplemented with vitamin A or myo-inositol (B10.A and B10.A [18R]). Fetuses from dams of all strains fed the diet supplemented with vitamin A had significantly increased frequencies of microphthalmia; the frequency of microphthalmia was moderately but not significantly increased in one of the two strains fed the diet supplemented with myo-inositol (B10.A[15R] but not B10.A[18R]). RP TYAN, ML (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,111M,LOS ANGELES,CA 90073, USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD OCT PY 1995 VL 210 IS 1 BP 77 EP 80 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RV747 UT WOS:A1995RV74700012 PM 7675802 ER PT J AU TREVINO, RJ HUNT, J HOROWITZ, PM CHIRGWIN, JM AF TREVINO, RJ HUNT, J HOROWITZ, PM CHIRGWIN, JM TI CHINESE-HAMSTER RHODANESE CDNA - ACTIVITY OF THE EXPRESSED PROTEIN IS NOT BLOCKED BY A C-TERMINAL EXTENSION SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID BOVINE LIVER RHODANESE; SEQUENCE-ANALYSIS; RNA-POLYMERASE; CLONING; GENES AB We describe a cDNA from Chinese hamster ovary cells which encodes a protein 91 and 96% identical to bovine and rat mitochondrial rhodaneses, respectively. Recombinant protein was expressed from the cDNA in Escherichia coli, purified to homogeneity, and found to have kinetic properties nearly indistinguishable from those of the bovine enzyme, the only cloned rhodanese previously verified by characterization of the recombinant protein, The carboxyl-terminus of the enzyme is characterized by a duplicated tripeptide, which can be proteolytically processed in vivo. We constructed a mutant in which the last 5 amino acids were replaced by 28 residues of unrelated sequence. This protein was expressed, purified, and found to have kinetic constants similar to those of the wild-type enzyme. The functionally verified Chinese hamster rhodanese cDNA encodes a protein of 297 residues and differs from the rat enzyme at 13 positions. None of these substitutions occurs at residues suggested to play essential roles in catalysis or structural stabilization. (C) 1995 Academic Press, Inc. C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV ENDOCRINOL, SAN ANTONIO, TX 78284 USA. UNIV TEXAS, HLTH SCI CTR, DEPT BIOCHEM, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, RES SERV, SAN ANTONIO, TX 78284 USA. FU NIEHS NIH HHS [ES 05729]; NIGMS NIH HHS [GM 25177] NR 31 TC 4 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 EI 1096-0279 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD OCT PY 1995 VL 6 IS 5 BP 693 EP 699 DI 10.1006/prep.1995.1091 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA RW190 UT WOS:A1995RW19000018 PM 8535164 ER PT J AU DIETRILL, M HOLLAND, J AF DIETRILL, M HOLLAND, J TI A MODEL CURRICULUM FOR TRAINING IN PSYCHO-ONCOLOGY SO PSYCHO-ONCOLOGY LA English DT Article ID CANCER-PATIENTS; CHRONIC ILLNESS; CHILDREN; CARE; ADJUSTMENT; PHYSICIANS; ILL; ADOLESCENTS; EDUCATION; LEUKEMIA AB The increased awareness of the cancer patient's psychosocial needs in the past few years has led to the development of training programs for health professionals working in oncology. Given the diversity of training goals, professionals involved in the care of patients, institutional resources and local needs, there is a lack of uniform criteria to train specialists in the field of psyche-oncology, This paper describes a model for a one-year curriculum the objective of which is to establish minimal standards of training to become a professional who is subspecialized in adult or child and adolescent psyche-oncology, The curriculum primarily consists of a didactic and a skills development components. Selection of trainees and faculty as well as teaching tools and evaluation of the curriculum are described. The second part of the model curriculum contains specific recommendations that address the particular educational needs of specific oncological disciplines (oncologists, nurses, social workers) and volunteers. In addition, the need for multidisciplinary teams in oncology settings is emphasized. Defining minimum standards for training across institutions and even nations will not only improve patient care but will also contribute to define psyche-oncology as a discipline. C1 CORNELL UNIV,SCH MED,MEM SLOAN KETTERING CANC CTR,ITHACA,NY 14853. RP DIETRILL, M (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 93 TC 12 Z9 12 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD OCT PY 1995 VL 4 IS 3 BP 169 EP 182 DI 10.1002/pon.2960040302 PG 14 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA TB441 UT WOS:A1995TB44100001 ER PT J AU LANGLEY, RE QUARTUCCIO, SG KENNEALEY, PT COLEMAN, CN BUMP, EA AF LANGLEY, RE QUARTUCCIO, SG KENNEALEY, PT COLEMAN, CN BUMP, EA TI EFFECT OF CELL-CYCLE STAGE, DOSE-RATE AND REPAIR OF SUBLETHAL DAMAGE ON RADIATION-INDUCED APOPTOSIS IN F9 TERATOCARCINOMA CELLS SO RADIATION RESEARCH LA English DT Article ID DNA FRAGMENTATION; P53; DEATH; GENE; IRRADIATION; THYMOCYTES; EXPRESSION; MUTATIONS; CANCER; LINES AB There are at least two different modes of cell death after treatment with ionizing radiation. The first is a failure to undergo sustained cell division despite metabolic survival, and we refer to this end point as ''classical reproductive cell death.'' The second is a process that results in loss of cell integrity. This second category includes cellular necrosis as well as apoptosis. Earlier studies in our laboratory showed that the predominant mechanism of cell death for irradiated F9 cells is apoptosis, and there is no indication that these cells die by necrosis. We have therefore used cells of this cell line to reassess basic radiobiological principles with respect to apoptosis. Classical reproductive cell death was determined by staining colonies derived from irradiated cells and scoring colonies of less than 50 cells as reproductively dead and colonies of more than 50 cells as survivors. Cells that failed to produce either type of colony (detached from the plate or disintegrated) were scored as having undergone apoptosis. Using these criteria we found that the fraction of the radiation-killed F9 cells that died by apoptosis did not vary when cells were irradiated at different stages of the cell cycle despite large variations in overall survival. This suggests that the factors that influence radiation sensitivity throughout the cell cycle have an equal impact on apoptosis and classical reproductive cell death. There was no difference in cell survival between split doses and single doses of X rays, suggesting that sublethal damage repair is not a factor in radiation-induced apoptosis of F9 cells. Apoptosis was not affected by changes in dose rate in the range of 0.038-4.96 Gy/min. (C) 1995 by Radiation Research Society C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA46776] NR 48 TC 17 Z9 17 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD OCT PY 1995 VL 144 IS 1 BP 90 EP 96 DI 10.2307/3579240 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA RX681 UT WOS:A1995RX68100012 PM 7568777 ER PT J AU HULKA, CA SMITH, BL SGROI, DC TAN, LJ EDMISTER, WB SEMPLE, JP CAMPBELL, T KOPANS, DB BRADY, TJ WEISSKOFF, RM AF HULKA, CA SMITH, BL SGROI, DC TAN, LJ EDMISTER, WB SEMPLE, JP CAMPBELL, T KOPANS, DB BRADY, TJ WEISSKOFF, RM TI BENIGN AND MALIGNANT BREAST-LESIONS - DIFFERENTIATION WITH ECHO-PLANAR MR-IMAGING SO RADIOLOGY LA English DT Article; Proceedings Paper CT 1994 RSNA Scientific Assembly CY NOV 27-DEC 02, 1994 CL CHICAGO, IL SP Radiol Soc N Amer DE BREAST NEOPLASMS, MR ID TUMOR ANGIOGENESIS; MAGNETIC-RESONANCE; GADOLINIUM-DTPA; GD-DTPA; SUPPRESSION; CARCINOMA; NMR AB PURPOSE: To quantify dynamic enhancement of breast lesions with echo-planar and conventional magnetic resonance (MR) imaging, to correlate these data with histologic findings and vessel density, and to evaluate the effect of T1 values on enhancement data. MATERIALS AND METHODS: Twenty female patients with 22 breast lesions underwent conventional and echo-planar MR imaging. T1 values, change in gadopentetate dimeglumine concentration, and extraction-flow products were calculated with echo-planar imaging data and were correlated with histologic findings and microvessel density. RESULTS: T1 values of cancers were not statistically significantly shorter. Cancers had more rapid uptake and higher extraction-flow products (P < .02). Sensitivity was 86% and specificity was 93% for diagnosis of malignancy. Microvessel density was higher far malignant lesions (P < .02) with an overall positive (not statistically significant) correlation between extraction-flow product and microvessel density. CONCLUSION Echo-planar imaging appears promising for quantification of breast lesion enhancement. Microvessel data indicate that tumor angiogenesis affects enhancement. C1 MASSACHUSETTS GEN HOSP,CTR NUCL MAGNET RESONANCE,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT PATHOL,BOSTON,MA 02111. RP HULKA, CA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 27 TC 163 Z9 167 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 1995 VL 197 IS 1 BP 33 EP 38 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RV899 UT WOS:A1995RV89900007 PM 7568850 ER PT J AU BEACHE, GM WEDEEN, VJ WEISSKOFF, RM OGARA, PT PONCELET, BP CHESLER, DA BRADY, TJ ROSEN, BR DINSMORE, RE AF BEACHE, GM WEDEEN, VJ WEISSKOFF, RM OGARA, PT PONCELET, BP CHESLER, DA BRADY, TJ ROSEN, BR DINSMORE, RE TI INTRAMURAL MECHANICS IN HYPERTROPHIC CARDIOMYOPATHY - FUNCTIONAL MAPPING WITH STRAIN-RATE MR-IMAGING SO RADIOLOGY LA English DT Article DE CARDIOMYOPATHY, HYPERTROPHIC,; HEART, DISEASES; HEART FUNCTION; HEART, MR; MAGNETIC RESONANCE (MR), PHYSICS; MAGNETIC RESONANCE (MR), TECHNOLOGY ID HEART WALL MOTION; SPATIAL MODULATION; MAGNETIZATION; RELAXATION AB PURPOSE: To characterize systolic and diastolic intramural mechanics in hypertrophic cardiomyopathy (HCM) with a new metric of contractile activity. MATERIALS AND METHODS: Eleven healthy subjects and eight patients with HCM underwent velocity-encoded echo-planar magnetic resonance (MR) imaging (6-8-frame gated breath-hold movies, 3 x 3-mm resolution). A scalar strain rate (SR) parameter was compared with wall thickness and symptoms. RESULTS: The normal pattern of SR included regional uniformity, a monotonically increasing subepicardial to subendocardial gradient, and minimum transmural shear rate. In HCM, heterogeneity of SRs increased in diastole. Regional diastolic SR correlated with regional wall thickness (r = .785, P = .0001). Interobserver global SR assignment agreed in seven of eight patients. All four patients with New York Heart Association class 1 disease had a low global SR deficit score, whereas three of four patients with class 2 or 3 disease had a high SR deficit score (Spearman r = .775, P = .187). CONCLUSION: SR characterization may provide an objective measure of disease course in HCM. C1 MASSACHUSETTS GEN HOSP,DIV CARDIAC RADIOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MED SERV,CARDIAC UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. RP BEACHE, GM (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR NMR,RM 2301,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [5T32 CA09502] NR 30 TC 23 Z9 23 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 1995 VL 197 IS 1 BP 117 EP 124 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RV899 UT WOS:A1995RV89900020 PM 7568808 ER PT J AU SHIOTA, G KAWASAKI, H NAKAMURA, T SCHMIDT, EV AF SHIOTA, G KAWASAKI, H NAKAMURA, T SCHMIDT, EV TI CHARACTERIZATION OF DOUBLE TRANSGENIC MICE EXPRESSING HEPATOCYTE GROWTH-FACTOR AND TRANSFORMING GROWTH-FACTOR-ALPHA SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY LA English DT Article ID CELLS; RAT AB Hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF alpha) are potent mitogens for mature hepatocytes in primary culture (Nakamura, Et al. 1984, Mead et al., 1989). However, these cytokines have completely different effects on tumor cell growth (Jhappan et al., 1990, Shiota et al, 1992). To clarify dual effects of these cytokines in liver, we developed double transgenic mice of HGF and TGF alpha using albumin promoter-HGF cDNA transgenic mice (AlbHGF) and metallothionein promoter-TGF alpha transgenic mice (MthTGF alpha). Double transgenic mice were examined on DNA synthesis, c-myc mRNA and occurrence of hepatocelular carcinoma (HCC). Higher labeling indices using BrDU were observed, in sequence, in AlbHGF mice, AlbHGF/MthTGF alpha, MthTGF alpha and wild type mice. Hepatic expression of c-myc mRNA in AlbHGF mice was elevated, compared to that in AlbHGF/MthTGF alpha or MthTGF alpha mice. After long-term observation, MthTGF alpha mice developed HCC in 6/10 (60%), whereas AlbHGF/MthTGF alpha mice developed HCC in 3/9 (33%). These data suggest that HGF is the potent mitogen, stimulating DNA synthesis and up-regulating c-myc mRNA. In addition, HGF may excert some inhibitory effect on occurrence of HCC by TGF alpha. C1 OSAKA UNIV,SCH MED,BIOMED RES CTR,DIV BIOCHEM,OSAKA 553,JAPAN. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RP SHIOTA, G (reprint author), TOTTORI UNIV,SCH MED,DEPT INTERNAL MED 2,YONAGO,TOTTORI 683,JAPAN. NR 18 TC 24 Z9 24 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 SN 1078-0297 J9 RES COMMUN MOL PATH JI Res. Commun. Mol. Pathol. Pharmacol. PD OCT PY 1995 VL 90 IS 1 BP 17 EP 24 PG 8 WC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy GA TC935 UT WOS:A1995TC93500002 PM 8581343 ER PT J AU LEUNIG, M YUAN, F GERWECK, LE BERK, DA JAIN, RK AF LEUNIG, M YUAN, F GERWECK, LE BERK, DA JAIN, RK TI QUANTITATIVE-ANALYSIS OF ANGIOGENESIS AND GROWTH OF BONE - EFFECT OF INDOMETHACIN EXPOSURE IN A COMBINED IN-VITRO IN-VIVO APPROACH SO RESEARCH IN EXPERIMENTAL MEDICINE LA English DT Article DE INDOMETHACIN; BONE FORMATION; ANGIOGENESIS; INTRAVITAL MICROSCOPY; DORSAL SKINFOLD CHAMBER; ORGAN CULTURE ID ANTIINFLAMMATORY DRUGS; INTRAVITAL MICROSCOPY; FRACTURE REPAIR; INVITRO; RATS; MICE; NEOVASCULARIZATION; MICROHEMODYNAMICS; PROSTAGLANDIN-E2; METABOLISM AB Nonsteroidal anti-inflammatory agents have been used experimentally and clinically to suppress a variety of physiological events, including angiogenesis and formation of bone. The exact mechanisms by which indomethacin alters skeletal tissue generation are unknown, due in part to methodological limitations. By the use of an organ culture assay and an animal model using intravital microscopy in mice bearing dorsal skinfold chambers, the effect of indomethacin on growth and angiogenesis of neonatal femora was characterized over 16 days. In both assays, femora significantly elongated with time(P<0.05). The in vitro growth rate was more rapid than in vivo and dependent on the serum concentration, culture medium and age of mice. Although enhancing the serum content promoted cellular proliferation in organ culture, it dose-dependently suppressed femoral elongation, leading at 20% fetal calf serum to growth rates identical to those observed in vivo. Indomethacin supplementation (2 and 10 mg l(-1)) significantly accelerated longitudinal femoral growth in organ culture (P<0.05), whereas in vivo indomethacin (2 mg kg(-1)) did not modulate either angiogenesis or elongation of bone. Our in vitro data propose a central role of serum in the regulation of bone formation. Although indomethacin altered femoral,oowth in vitro, our findings do not suggest that indomethacin suppresses angiogenesis or growth of bone in vivo. The complexity of physiological events in vivo may be obscuring a detectable effect. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Yuan, Fan/A-1287-2011; Berk, David/A-4863-2012; Leunig, Michael/E-7951-2017 OI Berk, David/0000-0002-3855-6886; Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [CA-22860, CA-56591] NR 45 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0300-9130 J9 RES EXP MED JI Res. Exp. Med. PD OCT PY 1995 VL 195 IS 5 BP 275 EP 288 DI 10.1007/BF02576798 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TC547 UT WOS:A1995TC54700003 PM 8578003 ER PT J AU WELLER, EA CATALANO, PJ WILLIAMS, PL AF WELLER, EA CATALANO, PJ WILLIAMS, PL TI IMPLICATIONS OF DEVELOPMENTAL TOXICITY STUDY DESIGN FOR QUANTITATIVE RISK ASSESSMENT SO RISK ANALYSIS LA English DT Article DE BENCHMARK DOSE; DESIGN; DEVELOPMENTAL TOXICOLOGY; DOSE-RESPONSE MODELING; RISK ASSESSMENT ID DOSE-RESPONSE; MODELS; EXTRAPOLATION AB Standard experimental designs for conducting developmental toxicity studies typically include three- or four-dose levels in addition to a control group. Some researchers have suggested that designs with more exposure groups would improve dose-response characterization and risk estimation. Such proposals have not, however, been supported by the results of simulation studies, which instead back the use of fewer dose levels. This discrepancy is partly due to using a known dose-response pattern to generate data, making model choice obvious. While the carcinogenicity literature has explored implications of different study designs, little attention has been given to the role of design in developmental toxicity risk assessment (or noncancer toxicology in general). in this research, we explore the implications of various experimental designs for developmental toxicity by resampling data from a large study of 2,4,5-trichlorophenoxyacetic acid in mice. We compare the properties of benchmark dose (BMD) estimation for different design strategies by randomly selecting animals within particular dose groups from the entire 2,4,5-T database of over 77,000 birth outcomes to create smaller ''pseudo-studies'' that are representative of standard bioassay sample sizes. Our results show that experimental designs which include more dose levels have advantages in terms of risk characterization and estimation. C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RP WELLER, EA (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 17 TC 12 Z9 12 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD OCT PY 1995 VL 15 IS 5 BP 567 EP 574 DI 10.1111/j.1539-6924.1995.tb00753.x PG 8 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA TJ474 UT WOS:A1995TJ47400004 ER PT J AU TSUANG, MT FARAONE, SV AF TSUANG, MT FARAONE, SV TI THE CASE FOR HETEROGENEITY IN THE ETIOLOGY OF SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Review ID MONOZYGOTIC TWINS DISCORDANT; FAMILIAL SPORADIC DISTINCTION; CEREBRAL VENTRICULAR SIZE; PSEUDOAUTOSOMAL LOCUS; PERINATAL COMPLICATIONS; OBSTETRIC COMPLICATIONS; PRENATAL EXPOSURE; INFLUENZA EPIDEMICS; ADULT SCHIZOPHRENIA; CEREBROSPINAL-FLUID AB To confirm etiological heterogeneity, it is required that schizophrenic patients may be separated into at least two classes having different known etiologies and, perhaps, different pathophysiological signatures. In contrast, the homogeneity hypothesis asserts that there is a single necessary and sufficient cause or configuration of causes of schizophrenia. Because the link between phenotypic heterogeneity and etiological heterogeneity is tenuous, attempts to use purely phenotypic data to infer etiologic heterogeneity must be viewed cautiously. We examined three candidate causes for schizophrenia: genes, obstetric complications and viral infection. Cytogenetic studies show that some rare cases of schizophrenia are due to gross abnormalities of chromosomes. As for the large majority of schizophrenic patients, the candidate cause data most certainly reject the most parsimonious version of the hypothesis of etiological homogeneity: that all schizophrenia is caused by exactly the same pattern of genetic mutations, birth related complications and exposure to the same viral infections. We conclude that the heterogeneity debate should consider the possibility of rewording the question: 'Heterogeneity: yes or no?' to 'Heterogeneity: how much?' C1 BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02115. RP TSUANG, MT (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHIAT,BOSTON,MA 02115, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [5 UO1 MH46318-02, 1 R01MH41879-01, 1 R37MH43518-01] NR 149 TC 109 Z9 112 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT PY 1995 VL 17 IS 2 BP 161 EP 175 DI 10.1016/0920-9964(95)00057-S PG 15 WC Psychiatry SC Psychiatry GA TE002 UT WOS:A1995TE00200005 PM 8562491 ER PT J AU FUCHS, CS MAYER, RJ AF FUCHS, CS MAYER, RJ TI ADJUVANT CHEMOTHERAPY FOR COLON AND RECTAL-CANCER SO SEMINARS IN ONCOLOGY LA English DT Review ID LARGE BOWEL-CANCER; NSABP CLINICAL-TRIALS; METASTATIC COLORECTAL-CARCINOMA; RECURRENCE FOLLOWING SURGERY; RANDOMIZED CONTROLLED TRIAL; HIGH-DOSE LEUCOVORIN; CURATIVE RESECTION; ONCOLOGY-GROUP; GENETIC ALTERATIONS; METHYL-CCNU C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA. RP FUCHS, CS (reprint author), DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [K07 CA66385-01] NR 132 TC 24 Z9 24 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1995 VL 22 IS 5 BP 472 EP 487 PG 16 WC Oncology SC Oncology GA RZ178 UT WOS:A1995RZ17800006 PM 7570058 ER PT J AU MORRELL, MJ BADR, MS HARMS, CA DEMPSEY, JA AF MORRELL, MJ BADR, MS HARMS, CA DEMPSEY, JA TI THE ASSESSMENT OF UPPER AIRWAY PATENCY DURING APNEA USING CARDIOGENIC OSCILLATIONS IN THE AIR-FLOW SIGNAL SO SLEEP LA English DT Article DE PULSE ARTIFACT; CENTRAL APNEA; NREM SLEEP; UPPER AIRWAY ID SLEEP; DOGS AB We investigated the relationship between airway patency and the occurrence of cardiogenic related oscillations in the airflow signal during 67 apneas occurring in non-rapid eye movement sleep in eight subjects. Spontaneously occurring apneas and apneas induced by mechanical ventilation were analyzed, Airway occlusion was determined by direct observation of the pharyngeal lumen using fiberoptic endoscopy. The presence or absence of cardiogenic oscillations was determined from an expanded airflow signal by an investigator blinded to the airway patency. Of the total 67 apneas, complete airway occlusion occurred during 51, and the airway remained patent throughout in 16. Cardiogenic oscillations were seen throughout 39 of the 51 occluded apneas and throughout 9 of the 16 apneas with the airway patent. There was no relationship between the occurrence of cardiogenic oscillations and airway patency. In addition, in a canine model where the upper airway was anatomically isolated, cardiogenic oscillations were evident during apneas in pressure signals recorded from the isolated upper airway and in airflow signals at the tracheal stoma. We conclude that cardiogenic oscillations cannot be used to predict airway patency during apnea. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT MED,MADISON,WI. RP MORRELL, MJ (reprint author), UNIV WISCONSIN,SCH MED,DEPT PREVENT MED,JOHN RANKIN PULM MED LAB,504 N WALNUT ST,MADISON,WI 53705, USA. FU NHLBI NIH HHS [HL 02588] NR 8 TC 17 Z9 17 U1 0 U2 1 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PD OCT PY 1995 VL 18 IS 8 BP 651 EP 658 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA TD542 UT WOS:A1995TD54200005 PM 8560131 ER PT J AU FERNANDEZDELCASTILLO, C WARSHAW, AL AF FERNANDEZDELCASTILLO, C WARSHAW, AL TI CYSTIC TUMORS OF THE PANCREAS SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID ACINAR CELL CYSTADENOCARCINOMA; MUCIN-PRODUCING TUMOR; MICROCYSTIC ADENOMA; SEROUS CYSTADENOMA; LATENT MALIGNANCY; ENDOCRINE TUMOR; DUCTAL ECTASIA; NEOPLASMS; PSEUDOCYSTS; CARCINOMA AB Cystic neoplasms of the pancreas are relatively uncommon lesions that should not be confused with pancreatic pseudocysts. Guidelines for this differential diagnosis, the characteristics of the more common varieties, and the authors' experience with 130 cystic tumors are described. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP FERNANDEZDELCASTILLO, C (reprint author), MASSACHUSETTS GEN HOSP,ACC-464,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 64 TC 139 Z9 145 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD OCT PY 1995 VL 75 IS 5 BP 1001 EP & PG 0 WC Surgery SC Surgery GA RU708 UT WOS:A1995RU70800014 PM 7660245 ER PT J AU YOSHIMURA, M HERSHMAN, JM AF YOSHIMURA, M HERSHMAN, JM TI THYROTROPIC ACTION OF HUMAN CHORIONIC-GONADOTROPIN SO THYROID LA English DT Review ID NORMAL PREGNANT-WOMEN; THYROID-STIMULATING ACTIVITY; HUMAN TSH RECEPTORS; HYPEREMESIS GRAVIDARUM; LUTEINIZING-HORMONE; SIGNAL TRANSDUCTION; HYDATIDIFORM MOLES; MORNING SICKNESS; CELLS; HCG AB Hyperthyroidism or increased thyroid function has been reported in many patients with trophoblastic tumors. In these cases, greatly increased human chorionic gonadotropin (hCG) levels and suppressed TSH levels suggest that hCG has thyrotropic activity. Recent investigations have clarified the structural homology not only in the hCG and TSH molecules but also in their receptors, and this homology suggests the basis for the reactivity of hCG with the TSH receptor. The clinical significance of the thyrotropic action of hCG is now also recognized in normal pregnancy and hyperemesis gravidarum. Highly purified hLH binds to recombinant hTSH receptor and is about 10 times as potent as purified hCG in increasing cAMP. The beta-subunits of hCG and hLH share 85% sequence identity in their first 114 amino acids but differ in the carboxy-terminal peptide because hCG beta contains a 31-amino acid extension (beta-CTP). A recombinant mutant hCG that lacks beta-CTP showed almost identical potency to LH on stimulation of recombinant hTSH receptor. If intact hCG were as potent as hLH in regard to its thyrotropic activity, most pregnant women would become thyrotoxic. One of the roles of the beta-CTP may be to prevent overt hyperthyroidism in the first trimester of pregnancy when a large amount of hCG is produced by the placenta. Nicked hCG preparations, obtained from patients with trophoblastic disease or by enzymatic digestion of intact hCG, showed approximately 1.5- to 2-fold stimulation of recombinant hTSH receptor compared with intact hCG. This suggests that the thyrotropic activity of hCG may be influenced by the metabolism of the hCG molecule itself. Deglycosylation and/or desialylation of hCG enhances its thyrotropic potency. Basic hCG isoforms with lower sialic acid content extracted from hydatidiform moles were more potent in activating adenylate cyclase, and showed high bioactivity/immunoactivity (B/I) ratio in CHO cells expressing human TSH receptors. This is consistent with the finding that the beta-CTP truncated hCG with higher thyrotropic potency is substantially deglycosylated and desialylated in the beta-subunit relative to intact hCG because all four O-linked glycosylation sites occur within the missing C-terminal extension. The desialylated hCG variant also interacts directly with recombinant hTSH receptors transfected into human thyroid cancer cells. There is thyroid-stimulating activity in sera of normal pregnant women, and this correlates with serum hCG levels. The thyroid gland of normal pregnant women may be stimulated by hCG to secrete slightly excessive quantities of T-4 and induce a slight suppression of TSH, perhaps being about 1 mU/L less than nongravid levels, but not high enough to induce overt hyperthyroidism. Maternal thyroid glands may secrete more thyroid hormone during early pregnancy in response to the thyrotropic activity of hCG that overrides the normal operation of the hypothalamic-pituitary-thyroid feedback system. Biochemical hyperthyroidism associated with hyperemesis gravidarum has been attributed to hCG. In patients with hyperemesis gravidarum, thyrotropic activity in serum correlated with hCG immunoreactivity, and the severity of vomiting as indicated by clinical and biochemical parameters correlated with the degree of thyroid stimulation. To understand the thyrotropic action of hCG, it is necessary to know whether hCG activates the same domain of the TSH receptor as does TSH. The identification of the molecular structure of the hCG isoform with the highest thyrotropic potency will resolve the enigma of gestational thyrotoxicosis and the hyperthyroidism associated with trophoblastic disease and hCG-producing tumors. C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV ENDOCRINOL & METAB,LOS ANGELES,CA 90073. KANSAI MED UNIV,DEPT INTERNAL MED 2,OSAKA,JAPAN. NR 61 TC 142 Z9 146 U1 0 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD OCT PY 1995 VL 5 IS 5 BP 425 EP 434 DI 10.1089/thy.1995.5.425 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TF020 UT WOS:A1995TF02000014 PM 8563483 ER PT J AU WALLACE, EL CHURCHILL, WH SURGENOR, DM AN, J CHO, G MCGURK, S MURPHY, L AF WALLACE, EL CHURCHILL, WH SURGENOR, DM AN, J CHO, G MCGURK, S MURPHY, L TI COLLECTION AND TRANSFUSION OF BLOOD AND BLOOD COMPONENTS IN THE UNITED-STATES, 1992 SO TRANSFUSION LA English DT Article ID REPLACEMENT; DISEASE; PLASMA AB Background: Studies were conducted to measure the state of the United States' national blood resource in 1992 and changes therein from 1989. Study Design and Methods: With data supplied by the American Red Cross and the American Association of Blood Banks, as well as data from a stratified random-sample survey of 3350 non-American Association of Blood Banks hospitals, statistical methods were applied to estimate national blood activities in 1992. Results: The total US blood supply in 1992 was 13,794,000 units, a decrease of 3.1 percent from 1989. Some 11,307,000 red cell units were transfused to 3,772,000 patients, an average of 3.0 units per transfused patient. Preoperative autologous blood deposits totaled 1,117,000 units, a 70-percent increase over 1989. Of this number, 566,000 units (50.7%) were transfused, 5,000 (4.4%) transferred to the allogeneic supply, and 546,000 (48.9%) discarded. Of 436,000 directed-donation units, 136,000 (31.2%) were transfused, 57,000 (13.1%) transferred to allogeneic supply, and 243,000 (55.7%) discarded. The total allogeneic blood supply, including imports, decreased by 7.4 percent from 1989, and allogeneic blood transfusions, including those to children, decreased by 8.6 percent. Over 8,300,000 platelet units were transfused; of these, some 3,600,000 were apheresis platelets. In addition, 2,255,000 units of plasma and 939,000 units of cryoprecipitate were transfused. Conclusion:While the US blood supply was adequate for transfusion needs in 1992, blood collections and red cell transfusions had decreased substantially since 1989. C1 CTR BLOOD RES,BOSTON,MA 02115. CTR MANAGEMENT SYST,SNOWMASS VILLAGE,CO. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL,BLOOD BANK,BOSTON,MA 02115. SUNY BUFFALO,SCH MANAGEMENT,BUFFALO,NY. FU NHLBI NIH HHS [HL-33774] NR 27 TC 153 Z9 156 U1 0 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 BP 802 EP 812 DI 10.1046/j.1537-2995.1995.351096026360.x PG 11 WC Hematology SC Hematology GA TA448 UT WOS:A1995TA44800003 PM 7570909 ER PT J AU BENJAMIN, RJ LINSLEY, L AXELROD, JD CHURCHILL, WH SIEFF, C SHULMAN, LN ELIAS, A AYASH, L MALACHOWSKI, ME UHL, L GAYNES, L MCCAULEY, M THOMPSON, L MAZANET, R ANTMAN, K SCHNIPPER, L TEPLER, I ANTIN, JH WHEELER, C AF BENJAMIN, RJ LINSLEY, L AXELROD, JD CHURCHILL, WH SIEFF, C SHULMAN, LN ELIAS, A AYASH, L MALACHOWSKI, ME UHL, L GAYNES, L MCCAULEY, M THOMPSON, L MAZANET, R ANTMAN, K SCHNIPPER, L TEPLER, I ANTIN, JH WHEELER, C TI THE COLLECTION AND EVALUATION OF PERIPHERAL-BLOOD PROGENITOR CELLS SUFFICIENT FOR REPETITIVE CYCLES OF HIGH-DOSE CHEMOTHERAPY SUPPORT SO TRANSFUSION LA English DT Article ID COLONY-STIMULATING FACTOR; CANCER-PATIENTS; AUTOLOGOUS TRANSPLANTATION; FLOW-CYTOMETRY; STEM-CELLS; GRANULOCYTE; CYCLOPHOSPHAMIDE; CARBOPLATIN AB Background: The development of an optimized peripheral blood progenitor cell (PBPC) harvest protocol to provide support for repetitive chemotherapy cycles is described. Study Design and Methods: PBPCs mobilized by cyclophosphamide plus granulocyte-colony-stimulating factor (G-CSF) were studied in 163 leukapheresis harvests from 26 lymphoma patients. Harvested cells were transfused with two chemotherapy cycles and with an autologous bone marrow transplant. Progenitor cell content was examined in the context of hematopoietic engraftment. Results: Mobilization allowed the harvest of large numbers of PBPCs. Peak harvests tended to occur after the recovering white cell count exceeded 10 x 10(9) per L. CD34+ lymphomononuclear cell (MNC) and colony-forming units-granulocyte-macrophage (CFU-GM) counts correlated poorly, but both measures peaked within 24 hours of each other in 21 of 26 patients, which demonstrated PBPC mobilization. Engraftment of platelets (>50 x 10(9)/L) and granulocytes (>500 x 10(6)/L) was achieved in a median of 20.5 and 16 days, respectively. A minimum number of progenitors necessary to ensure engraftment could be derived. Conclusion: Cyclophosphamide and G-CSF allowed the harvest of sufficient PBPCs to support multiple rounds of chemotherapy Harvest should commence when the recovery white cell count exceeds 10 x 1O(9) per L. PBPC harvest CD34+ MNC counts are as useful as CFU-GM results in the assessment of PBPC content, and they may allow harvest protocols to be tailored to individual patients. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BLOOD BANK,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. RP BENJAMIN, RJ (reprint author), HARVARD UNIV,SCH MED,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA58661, CA39542] NR 31 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 BP 837 EP 844 DI 10.1046/j.1537-2995.1995.351096026365.x PG 8 WC Hematology SC Hematology GA TA448 UT WOS:A1995TA44800008 PM 7570914 ER PT J AU CONNOLLY, J HULSE, K TERUYA, J STOWELL, C AF CONNOLLY, J HULSE, K TERUYA, J STOWELL, C TI RESULTS OF A HCV DONOR REENTRY PROTOCOL FROM A HOSPITAL-BASED DONOR CENTER SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP A26 EP A26 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800293 ER PT J AU SCHOTT, D BARRETT, B ANDERSON, K ZAIKEN, E DUMONT, LJ AF SCHOTT, D BARRETT, B ANDERSON, K ZAIKEN, E DUMONT, LJ TI MODIFICATION OF A NAGEOTTE SCREENING METHOD FOR SELECTION OF LEUKOCYTE-REDUCED APHERESIS PLATELETS SO TRANSFUSION LA English DT Meeting Abstract C1 DFCI,BOSTON,MA. BCT,COBE,LAKEWOOD,CO. RI Dumont, Larry/B-3994-2011 OI Dumont, Larry/0000-0002-1715-0748 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S78 EP S78 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800077 ER PT J AU STOWELL, C AF STOWELL, C TI EPOIETIN ALFA REDUCES PERIOPERATIVE TRANSFUSION REQUIREMENTS IN PATIENTS UNDERGOING MAJOR ORTHOPEDIC-SURGERY SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BLOOD TRANSFUS SERV,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S106 EP S106 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800105 ER PT J AU VAMVAKAS, EC PINEDA, AA WEINSHENKER, BG AF VAMVAKAS, EC PINEDA, AA WEINSHENKER, BG TI METAANALYSIS OF CLINICAL-STUDIES OF THE EFFICACY OF PLASMA-EXCHANGE IN THE TREATMENT OF CHRONIC PROGRESSIVE MULTIPLE-SCLEROSIS SO TRANSFUSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1995 VL 35 IS 10 SU S BP S214 EP S214 PG 1 WC Hematology SC Hematology GA TB478 UT WOS:A1995TB47800212 ER PT J AU KOLODNER, RD AF KOLODNER, RD TI MISMATCH REPAIR - MECHANISMS AND RELATIONSHIP TO CANCER SUSCEPTIBILITY SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; SYSTEM; ENDONUCLEASE; GLYCOSYLASE; SEQUENCE; CLONING; HOMOLOG; CELLS AB DNA mismatch-repair systems exist that repair mispaired bases formed during DNA replication, genetic recombination and as a result of damage to DNA. Some components of these systems are conserved in prokaryotes and eukaryotes. Genetic defects in mismatch-repair genes play an important role in common cancer-susceptibility syndromes and sporadic cancers. C1 HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. RP KOLODNER, RD (reprint author), DANA FARBER CANC INST, DIV HUMAN CANC GENET, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA67151]; NIGMS NIH HHS [GM50006] NR 49 TC 255 Z9 261 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD OCT PY 1995 VL 20 IS 10 BP 397 EP 401 DI 10.1016/S0968-0004(00)89087-8 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TB558 UT WOS:A1995TB55800006 PM 8533151 ER PT J AU WEAVER, DT AF WEAVER, DT TI WHAT TO DO AT AN END - DNA DOUBLE-STRAND-BREAK REPAIR SO TRENDS IN GENETICS LA English DT Review ID V(D)J RECOMBINATION; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; HUMAN CHROMOSOME-8; PROTEIN-KINASE; SCID MUTATION; KU ANTIGEN; MUTANTS; MICE; CELLS AB Repairing chromosome breaks is essential to cell survival. A major lethal effect of ionizing radiation (IR) damage is the creation of double-strand DNA breaks. Recently, a number of mammalian cell mutants that are sensitive to IR damage have been described, revealing a unique repair pathway. The DNA-dependent protein kinase (DNA-PK) is necessary for double-strand-break repair and lymphoid V(D)J recombination. DNA-PK consists of three subunits: the Ku autoantigen heterodimer and a kinase (DNA-PKcs) that is deficient in mouse scid mutant cells. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RP WEAVER, DT (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 51 TC 184 Z9 185 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 1995 VL 11 IS 10 BP 388 EP 392 DI 10.1016/S0168-9525(00)89121-0 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA RW953 UT WOS:A1995RW95300009 PM 7482764 ER PT J AU LOUIS, DN GUSELLA, JF AF LOUIS, DN GUSELLA, JF TI A TIGER BEHIND MANY DOORS - MULTIPLE GENETIC PATHWAYS TO MALIGNANT GLIOMA SO TRENDS IN GENETICS LA English DT Review ID EPIDERMAL GROWTH-FACTOR; FACTOR RECEPTOR GENE; GLIOBLASTOMA-MULTIFORME; HUMAN ASTROCYTOMAS; P53; HETEROZYGOSITY; AMPLIFICATION; CHROMOSOME-10; EXPRESSION; MUTATIONS AB Malignant gliomas are the most common primary human brain tumours, but their classification remains controversial and effective therapies remain elusive. As a result, malignant gliomas have come under intense scientific scrutiny, in the hope of elucidating the molecular basis of glial tumourigenesis. These studies have yielded insights into the genetic events that underlie glioma formation and progression, and have shown multiple distinct genetic pathways that lead to the common malignant endpoint of glioblastoma multiforme. Such genetic pathways mirror clinicopathological avenues of glioma progression and suggest that molecular genetic approaches might have clinical utility in the coming years. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. RP LOUIS, DN (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA57683] NR 38 TC 171 Z9 171 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 1995 VL 11 IS 10 BP 412 EP 415 DI 10.1016/S0168-9525(00)89125-8 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA RW953 UT WOS:A1995RW95300013 PM 7482768 ER PT J AU BARRY, MJ FLEMING, C COLEY, CM WASSON, JH FAHS, MC OESTERLING, JE AF BARRY, MJ FLEMING, C COLEY, CM WASSON, JH FAHS, MC OESTERLING, JE TI SHOULD MEDICARE PROVIDE REIMBURSEMENT FOR PROSTATE-SPECIFIC ANTIGEN TESTING FOR EARLY DETECTION OF PROSTATE-CANCER .4. ESTIMATING THE RISKS AND BENEFITS OF AN EARLY DETECTION PROGRAM SO UROLOGY LA English DT Article ID DIGITAL RECTAL EXAMINATION; RADICAL PROSTATECTOMY; DECISION-ANALYSIS; INFORMED CONSENT; UNITED-STATES; COMPLICATIONS; PROGRESSION; POPULATION; ACCEPTANCE; SURVIVAL C1 MASSACHUSETTS GEN HOSP, CTR MED PRACTICES EVALUAT, BOSTON, MA 02114 USA. HLTH OUTCOMES ASSOCIATES, VANCOUVER, WA USA. DARTMOUTH COLL SCH MED, CTR EVALUAT CLIN SCI, HANOVER, NH USA. MT SINAI SCH MED, DEPT COMMUNITY MED, DIV HLTH ECON, NEW YORK, NY USA. MT SINAI SCH MED, INT LONGEV CTR US, NEW YORK, NY USA. UNIV MICHIGAN, DEPT SURG, DIV UROL, ANN ARBOR, MI 48109 USA. FU AHRQ HHS [HS 08397, HS 06336] NR 47 TC 38 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD OCT PY 1995 VL 46 IS 4 BP 445 EP 461 DI 10.1016/S0090-4295(99)80255-6 PG 17 WC Urology & Nephrology SC Urology & Nephrology GA RY868 UT WOS:A1995RY86800001 PM 7571211 ER PT J AU HUGHES, DB SMITH, AR HOPPE, R OWEN, JB HANLON, A WALLACE, M HANKS, GE AF HUGHES, DB SMITH, AR HOPPE, R OWEN, JB HANLON, A WALLACE, M HANKS, GE TI TREATMENT PLANNING FOR HODGKINS-DISEASE - A PATTERNS OF CARE STUDY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE TREATMENT PLANNING; PATTERNS OF CARE; RADIATION ONCOLOGY; HODGKINS DISEASE AB Purpose: To conduct a survey of the process of treatment planning for the radiation treatment of Hodgkin's Disease in the United States, and to compare survey results with consensus guidelines as determined by recognized experts. Methods and Materials: A consensus committee developed guidelines for the radiotherapeutic management of Hodgkin's Disease. A series of survey forms were designed to evaluate the standards of practice and compare these with the consensus guidelines. A total of 61 facilities divided evenly into the strata of academic, hospital based, and free standing had eligible Hodgkin's Disease cases. There were 275 eligible cases of Hodgkin's Disease evaluated. Data collected from the radiation oncology records included treatment-specific parameters such as energy, dose, blocking, and calculations, as well as treatment planning practices. Statistical analysis was performed on each data element and for all institution strata. Results: For a number of treatment parameters, there were some discrepancies noted between the current United States practice and the consensus guidelines. Some significant differences were found in practice between the stratified institution types. A representative sample of results are: the majority of Hodgkin's Disease patients are treated with x-ray energies in the recommended range, between 4 and 10 MV. Standard mantle (for upper extended field treatment) and modified spade (for lower extended held treatments) are the fields of choice for all types of facilities. The consensus guidelines recommended that dose calculations at multiple points be obtained; however, 15% of patients in the survey received only a single point calculation. Current irregular field dosimetry calculation software does not take account of inhomogeneities. Thirty percent of Hodgkin's Disease patients do not receive a gap calculation for the abutment of upper and lower extended fields. In 70% of treatment fields, no compensation is used. Very few patients receive any kind of in vivo dosimetry check. Conclusion: The survey served to verify that, in general, Hodgkin's Disease treatment planning at all strata of institution has kept pace with recommended practice as delineated in current literature and texts. Small pockets of practice still need improvement in technique and equipment. Changes in practice were identified that can contribute to improved dose uniformity and accuracy. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. STANFORD UNIV,STANFORD,CA 94305. AMER COLL RADIOL,PHILADELPHIA,PA. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. RP HUGHES, DB (reprint author), ST VINCENT HOSP & MED CTR,DEPT RADIAT ONCOL,9205 SW BARNES RD,PORTLAND,OR 97225, USA. FU NCI NIH HHS [N01-CM-87275] NR 3 TC 13 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 30 PY 1995 VL 33 IS 2 BP 519 EP 524 DI 10.1016/0360-3016(94)00605-K PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RW575 UT WOS:A1995RW57500034 PM 7673042 ER PT J AU HAUDENSCHILD, DR TONDRAVI, MM HOFER, U CHEN, Q GOETINCK, PF AF HAUDENSCHILD, DR TONDRAVI, MM HOFER, U CHEN, Q GOETINCK, PF TI THE ROLE OF COILED-COIL ALPHA-HELICES AND DISULFIDE BONDS IN THE ASSEMBLY AND STABILIZATION OF CARTILAGE MATRIX PROTEIN SUBUNITS - A MUTATIONAL ANALYSIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VON WILLEBRAND FACTOR; EXTRACELLULAR-MATRIX; VONWILLEBRAND-FACTOR; COLLAGEN; SITES; ORGANIZATION; DOMAINS; BINDING; HEPARIN; CHAIN AB Cartilage matrix protein (CMP) exists as a disulfide-bonded homotrimer in the matrix of cartilage, Each monomer consists of two CMP-A domains that are separated by an epidermal growth factor-like domain. A heptad repeat-containing tail makes up the carboxyl-terminal domain of the protein. The secreted form of CMP contains 12 cysteine residues numbered C1 through C12. Two of these are in each of the CMP-A domains, six are in the epidermal growth factor-like domain, and two are in the heptad repeat-containing tail. Two major categories of mutant CMPs were generated to analyze the oligomerization process of CMP: a mini-CMP and a heptad-less full-length CMP. The mini CMP consists of the CMP-A2 domain and the heptad repeat-containing tail. In addition, a number of mutations affecting C9 through C12 were generated within the full-length, the mini-, and the heptad-less CMPs, The mutational analysis indicates that the heptad repeats are necessary for the initiation of CMP trimerization and that the two cysteines in the heptad repeat-containing tail are both necessary and sufficient to form intermolecular disulfide bonds in either full-length or mini-CMP. The two cysteines within a CMP-A domain form an intradomain disulfide bond. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. RI Haudenschild, Dominik/B-2381-2008; Chen, Qian/C-4354-2011 OI Haudenschild, Dominik/0000-0001-9947-9864; Chen, Qian/0000-0003-4406-5618 FU NICHD NIH HHS [HD-22016]; NIGMS NIH HHS [P20 GM104937] NR 26 TC 33 Z9 33 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 29 PY 1995 VL 270 IS 39 BP 23150 EP 23154 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY054 UT WOS:A1995RY05400080 PM 7559460 ER PT J AU OHNO, H STEWART, J FOURNIER, MC BOSSHART, H RHEE, I MIYATAKE, S SAITO, T GALLUSSER, A KIRCHHAUSEN, T BONIFACINO, JS AF OHNO, H STEWART, J FOURNIER, MC BOSSHART, H RHEE, I MIYATAKE, S SAITO, T GALLUSSER, A KIRCHHAUSEN, T BONIFACINO, JS TI INTERACTION OF TYROSINE-BASED SORTING SIGNALS WITH CLATHRIN-ASSOCIATED PROTEINS SO SCIENCE LA English DT Article ID TRANS-GOLGI NETWORK; PLASMA-MEMBRANE; COATED VESICLES; CYTOPLASMIC DOMAIN; INVITRO BINDING; RECEPTOR; SEQUENCE; CLONING; TGN38; MOTIF AB Tyrosine-based signals within the cytoplasmic domain of integral membrane proteins mediate clathrin-dependent protein sorting in the endocytic and secretory pathways. A yeast two-hybrid system was used to identify proteins that bind to tyrosine-based signals. The medium chains (mu(1) and mu(2)) of two clathrin-associated protein complexes (AP-1 and AP-2, respectively) specifically interacted with tyrosine-based signals of several integral membrane proteins. The interaction was confirmed by in vitro binding assays. Thus, it is likely that the medium chains serve as signal-binding components of the clathrin-dependent sorting machinery. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. CHIBA UNIV,SCH MED,CTR BIOMED SCI,DIV MOLEC GENET,CHIBA 260,JAPAN. RI Yang, Chen/G-1379-2010; Saito, Takashi/C-9684-2009; Ohno, Hiroshi/L-7899-2014; OI Saito, Takashi/0000-0001-9495-3547; Ohno, Hiroshi/0000-0001-8776-9661; Bonifacino, Juan S./0000-0002-5673-6370 NR 35 TC 733 Z9 740 U1 5 U2 20 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 29 PY 1995 VL 269 IS 5232 BP 1872 EP 1875 DI 10.1126/science.7569928 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX194 UT WOS:A1995RX19400038 PM 7569928 ER PT J AU SEIDEN, MV PINS, MR KAUFFMAN, MG LYNCH, TJ BLOCH, KJ COLVIN, RB AF SEIDEN, MV PINS, MR KAUFFMAN, MG LYNCH, TJ BLOCH, KJ COLVIN, RB TI A 69-YEAR-OLD WOMAN WITH LUPUS-ERYTHEMATOSUS AND PAINFUL SKIN-LESIONS OF THE FEET - MULTIPLE-MYELOMA, WITH IGG-KAPPA SERUM-M COMPONENT - CRYOGLOBULINEMIA, TYPE-I - (OVERLAP SYNDROME OF CALCINOSIS, RAYNAUDS-PHENOMENON, ESOPHAGEAL DYSMOTILITY, SCLERODACTYL, AND TELANGIECTASIA [CREST] AND SYSTEMIC LUPUS-ERYTHEMATOSUS) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID LYMPHOMATOID GRANULOMATOSIS; LIVEDO RETICULARIS; VASCULITIS; CLASSIFICATION; ANTIBODIES; MALIGNANCY; FEATURES; CRITERIA C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP SEIDEN, MV (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 26 TC 10 Z9 10 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 28 PY 1995 VL 333 IS 13 BP 862 EP 868 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RW883 UT WOS:A1995RW88300008 ER PT J AU AVELINE, BM KOCHEVAR, IE REDMOND, RW AF AVELINE, BM KOCHEVAR, IE REDMOND, RW TI PHOTOCHEMISTRY OF N-HYDROXYPYRIDINE-2 THIONE DERIVATIVES - INVOLVEMENT OF THE 2-PYRIDYLTHIYL RADICAL IN THE RADICAL-CHAIN REACTION-MECHANISM SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SUBSTITUTED BENZENETHIYL RADICALS; RATE CONSTANTS; FLASH-PHOTOLYSIS; ADDITION RATES; VINYL MONOMERS; THIOHYDROXAMIC ESTERS; EXCITED RADICALS; ACYL DERIVATIVES; CARBON RADICALS; ENERGY-TRANSFER AB The primary and subsequent photochemistry of four N-hydroxypyridine-2-thione esters has been investigated by laser flash photolysis (lambda(exc) = 355 nm). A simple, high-yield synthetic method is given for their preparation with high purity. UV irradiation of these ester compounds was shown to lead specifically to the formation of benzyl, diphenylmethyl, tert-butyl, and benzoyloxyl radicals in addition to the 2-pyridylthiyl radical. in all cases, the initial photoinduced nitrogen-oxygen bond cleavage was found to occur in high quantum yield (Phi(N-O) approximate to 0.5) The radical species generated by this process (2-pyridylthiyl radical and carbon-centered or oxygen-centered radicals) were characterized and their reactivity toward several radical scavengers has been studied. An efficient delayed depletion of the N-hydroxypyridine-2-thione esters was also observed, leading to overall bleaching quantum yields, (Phi(B1), close to unity. We have demonstrated that the delayed consumption of ground-state ester was due to the reaction of the 2-pyridylthiyl radical with its precursor, occurring with a rate constant, k(r), of 3-4 x 10(9) M(-1) s(-1). This reaction, hitherto never proposed, leads to the formation of 2,2'-dipyridyl disulfide and further release of propagating radicals. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 52 TC 55 Z9 55 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 27 PY 1995 VL 117 IS 38 BP 9699 EP 9708 DI 10.1021/ja00143a013 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA RX712 UT WOS:A1995RX71200013 ER PT J AU PIWNICAWORMS, D RAO, VV KRONAUGE, JF CROOP, JM AF PIWNICAWORMS, D RAO, VV KRONAUGE, JF CROOP, JM TI CHARACTERIZATION OF MULTIDRUG-RESISTANCE P-GLYCOPROTEIN TRANSPORT FUNCTION WITH AN ORGANOTECHNETIUM CATION SO BIOCHEMISTRY LA English DT Article ID HEXAKIS 2-METHOXYISOBUTYL ISONITRILE; CHICK MYOCARDIAL-CELLS; PLASMA-MEMBRANE; DRUG TRANSPORT; HEART-CELLS; TECHNETIUM-99M-MIBI UPTAKE; INVIVO CIRCUMVENTION; CYCLOSPORINE-A; EXPRESSION; VESICLES AB Multidrug resistance (MDR) in mammalian cells and tumors is associated with overexpression of an similar to 170 kDa integral membrane efflux transporter, the MDR1 P-glycoprotein. Hexakis(2-methoxyisobutyl isonitrile)technetium(I) (Tc-SESTAMIBI), a gamma-emitting lipophilic cationic metallopharmaceutical, has recently been shown to be a P-glycoprotein transport substrate. Exploiting the negligible lipid membrane adsorption properties of this organometallic substrate, we studied the transport kinetics, pharmacology, drug binding, and modulation of P-glycoprotein in cell preparations derived from a variety of species and selection strategies, including SW-1573, V79, Alex, and CHO drug-sensitive cells and in 77A, LZ-8, and Alex/A.5 MDR cells. Rapid cell accumulation (t(1/2) approximate to 6 min) of the agent to a steady state was observed which was inversely proportional to immunodetectable levels of P-glycoprotein. Many MDR cytotoxic agents inhibited P-glycoprotein-mediated Tc-SESTAMIBI efflux, thereby enhancing organometallic cation accumulation. Median effective concentrations (EC(50); mu M) were as follows: vinblastine, 13; daunomycin, 55; idarubicin, 65; actinomycin D, 235; colchicine, minimal inhibition; adriamycin, no effect. P-glycoprotein modulators generally demonstrated significantly greater potency (EC(50); mu M): SDZ PSC 833, 0.08; cyclosporin A, 1.3; verapamil, 4.1; quinidine, 6.4; prazosin, >300. Modulator-induced enhancement up to 100-fold was observed with Hill coefficients approximate to 1, consistent with simple Michaelis-Menten kinetics. Vanadate was an efficacious transport inhibitor, while agents usually not included in the MDR phenotype were without effect. Scatchard analysis showed quinidine to be a noncompetitive inhibitor of P-glycoprotein-mediated Tc-SESTAMIBI transport, indicating allosteric effector sites on P-glycoprotein. The lipid bilayer adsorbing agents tetraphenyl berate and phloretin induced large increases in final Tc-SESTAMIBI accumulation, showing maximal accumulations 2-fold greater than classic MDR modulators and Hill coefficients much greater than 2. In V79 and 77A cells, modulators of PKC activity altered Tc-SESTAMLBI accumulation, while there was no indication of modulation of P-glycoproteinmediated Tc-SESTAMIBI transport by hypotonic buffer, extracellular ATP, Cl-, or K+ (membrane potential). While recognized and avidly transported by the P-glycoprotein at buffer concentrations as low as 7 pM, Tc-SESTAMTBI at up to 100 mu M only minimally modulated the cytotoxic action of colchicine, doxorubicin, or vinblastine in MDR cells. In conclusion, transport analysis with Tc-SESTAMIBI is a sensitive assay for detecting functional expression of low levels of P-glycoprotein and for the quantitative characterization of transporter modulation and regulation. The biochemical data favor a high K-m, high capacity allosterically modulated translocation mechanism for P-glycoprotein-mediated transport of this organometallic cation. In addition, the known physicochemical properties of Tc-SESTAMIBI combined with effects of the membrane adsorbing agents indicate that lipid-protein interactions are critical for transport of this metallopharmaceutical and would suggest that this drug gains access to protein transport domains from the lipid phase with rapid time constants. C1 WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL,ST LOUIS,MO 63110. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. RP PIWNICAWORMS, D (reprint author), WASHINGTON UNIV,SCH MED,MALLINCKRODT INST RADIOL,MOLEC RADIOPHARMACOL LAB,CAMPUS BOX 8225,ST LOUIS,MO 63110, USA. FU NHLBI NIH HHS [HL42966] NR 70 TC 96 Z9 100 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 26 PY 1995 VL 34 IS 38 BP 12210 EP 12220 DI 10.1021/bi00038a015 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX235 UT WOS:A1995RX23500015 PM 7547962 ER PT J AU COLL, JL BENZEEV, A EZZELL, RM FERNANDEZ, JLR BARIBAULT, H OSHIMA, RG ADAMSON, ED AF COLL, JL BENZEEV, A EZZELL, RM FERNANDEZ, JLR BARIBAULT, H OSHIMA, RG ADAMSON, ED TI TARGETED DISRUPTION OF VINCULIN GENES IN F9 AND EMBRYONIC STEM-CELLS CHANGES CELL MORPHOLOGY, ADHESION, AND LOCOMOTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENE TARGETING; CYTOSKELETON ID 3T3 CELLS; EXTRACELLULAR-MATRIX; CULTURED FIBROBLASTS; DEPENDENT REGULATION; PROTEIN EXPRESSION; FOCAL ADHESIONS; RETINOIC ACID; DIFFERENTIATION; FIBRONECTIN; CDNA AB Vinculin, a major constituent of focal adhesions and zonula adherens junctions, is thought to be involved in linking the microfilaments to areas of cell-substrate and cell-cell contacts, To test the role of vinculin in cell adhesion and motility, we used homologous recombination to generate F9 embryonal carcinoma and embryonic stem cell clones homozygous for a disrupted vinculin gene, When compared to wild-type cells, vinculin-mutant cells displayed a rounder morphology and a reduced ability to adhere and spread on plastic or fibronectin, Decreased adhesion of the mutant cells was associated with a reduction in lamellipodial extensions, as observed by time-lapse video microscopy. The locomotive activities of control F9 and the vinculin-null cells were compared in two assays. Loss of vinculin resulted in a 2.4-fold increase in cell motility. These results demonstrate an important role for vinculin in determining cell shape, adhesion, surface protrusive activity, and cell locomotion. C1 WEIZMANN INST SCI,DEPT MOLEC GENET & VIROL,IL-76100 REHOVOT,ISRAEL. LA JOLLA CANC RES FDN,LA JOLLA,CA 92037. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG RES LAB,BOSTON,MA 02129. RI Coll, Jean-Luc/G-2520-2013 OI Coll, Jean-Luc/0000-0002-2453-3552 FU NCI NIH HHS [CA 42302, CA 54233, P30 CA 30199] NR 36 TC 144 Z9 145 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 26 PY 1995 VL 92 IS 20 BP 9161 EP 9165 DI 10.1073/pnas.92.20.9161 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RX200 UT WOS:A1995RX20000032 PM 7568093 ER PT J AU UBEL, PA ARNOLD, RM AF UBEL, PA ARNOLD, RM TI THE UNBEARABLE RIGHTNESS OF BEDSIDE RATIONING - PHYSICIAN DUTIES IN A CLIMATE OF COST-CONTAINMENT SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HEALTH-CARE; RESOURCE-ALLOCATION; PRACTICE GUIDELINES; OREGON; INTERVENTIONS; INEVITABILITY; OSMOLALITY; DECISIONS; DOCTORS; QUALITY AB A local internist is in the process of ordering an intravenous pyelogram for a patient she suspects of having kidney problems, when a medical student shadowing her in clinic interrupts. The student wants to know why the physician is not ordering a low-osmolality contrast agent for the patient, having read that they are less likely to cause serious side effects than high-osmolality contrast agents, The physician realizes that: the medical student is correct, but rejects the suggestion, telling the student that ''low-osmolality contrast agents are the standard of care for low-risk patients.'' C1 UNIV PENN,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104. UNIV PENN,CTR BIOETH,PHILADELPHIA,PA 19104. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV PITTSBURGH,DIV GEN INTERNAL MED,PITTSBURGH,PA. UNIV PITTSBURGH,CTR MED ETH,PITTSBURGH,PA. RP UBEL, PA (reprint author), VET AFFAIRS MED CTR,111GM,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 50 TC 52 Z9 52 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD SEP 25 PY 1995 VL 155 IS 17 BP 1837 EP 1842 DI 10.1001/archinte.155.17.1837 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA RV804 UT WOS:A1995RV80400002 PM 7677549 ER PT J AU LERNER, TJ BOUSTANY, RMN ANDERSON, JW DARIGO, KL SCHLUMPF, K BUCKLER, AJ GUSELLA, JF HAINES, JL KREMMIDIOTIS, G LENSINK, IL SUTHERLAND, GR CALLEN, DF TASCHNER, PEM DEVOS, N VANOMMEN, GJB BREUNING, MH DOGGETT, NA MEINCKE, LJ LIU, ZY GOODWIN, LA TESMER, JG MITCHISON, HM ORAWE, AM MUNROE, PB JARVELA, IE GARDINER, RM MOLE, SE AF LERNER, TJ BOUSTANY, RMN ANDERSON, JW DARIGO, KL SCHLUMPF, K BUCKLER, AJ GUSELLA, JF HAINES, JL KREMMIDIOTIS, G LENSINK, IL SUTHERLAND, GR CALLEN, DF TASCHNER, PEM DEVOS, N VANOMMEN, GJB BREUNING, MH DOGGETT, NA MEINCKE, LJ LIU, ZY GOODWIN, LA TESMER, JG MITCHISON, HM ORAWE, AM MUNROE, PB JARVELA, IE GARDINER, RM MOLE, SE TI ISOLATION OF A NOVEL GENE UNDERLYING BATTEN-DISEASE, CLN3 SO CELL LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; MITOCHONDRIAL ATP SYNTHASE; HUMAN CHROMOSOME-16; LOCUS CLN3; PROTEIN; PEPTIDES; SITES; IDENTIFICATION; REQUIREMENTS; LOCALIZATION AB Batten disease (also known as juvenile neuronal ceroid lipofuscinosis) is a recessively inherited neurodegenerative disorder of childhood characterized by progressive loss of vision, seizures, and psychomotor disturbances. The Batten disease gene, CLN3, maps to chromosome 16p12.1. The so-called 56 chromosome haplotype defined by alleles at the D16S299 and D16S298 loci is shared by 73% of Batten disease chromosomes. Exon amplification of a cosmid containing D76S298 has yielded a candidate gene that is disrupted by a 1 kb genomic deletion in all patients carrying the 56 chromosome. Two separate deletions and a point mutation altering a splice site in three unrelated families have confirmed the candidate as the CLN3 gene. The disease gene encodes a novel 438 amino acid protein of unknown function. C1 HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02114 USA. DUKE UNIV, MED CTR, DIV PEDIAT NEUROL, DURHAM, NC 27710 USA. WOMENS & CHILDRENS HOSP, DEPT CYTOGENET & MOLEC GENET, ADELAIDE, SA 5006, AUSTRALIA. LEIDEN UNIV, DEPT HUMAN GENET, 2333 AL LEIDEN, NETHERLANDS. ERASMUS UNIV ROTTERDAM, DEPT CLIN GENET, 3015 GE ROTTERDAM, NETHERLANDS. LOS ALAMOS NATL LAB, DIV LIFE SCI, LOS ALAMOS, NM 87545 USA. LOS ALAMOS NATL LAB, CTR HUMAN GENOME STUDIES, LOS ALAMOS, NM 87545 USA. UCL, SCH MED, RAYNE INST, DEPT PEDIAT, LONDON WC1E 6JJ, ENGLAND. RP LERNER, TJ (reprint author), MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BOSTON, MA 02129 USA. RI Mitchison, Hannah/C-1891-2008; Mole, Sara/C-2024-2008; Haines, Jonathan/C-3374-2012; Sutherland, Grant/D-2606-2012; Callen, David/G-1975-2012; Jarvela, Irma/L-5836-2013 NR 48 TC 356 Z9 359 U1 1 U2 22 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 22 PY 1995 VL 82 IS 6 BP 949 EP 957 DI 10.1016/0092-8674(95)90274-0 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RW693 UT WOS:A1995RW69300011 ER PT J AU VONANDRIAN, UH HASSLEN, SR NELSON, RD ERLANDSEN, SL BUTCHER, EC AF VONANDRIAN, UH HASSLEN, SR NELSON, RD ERLANDSEN, SL BUTCHER, EC TI A CENTRAL ROLE FOR MICROVILLOUS RECEPTOR PRESENTATION IN LEUKOCYTE ADHESION UNDER FLOW SO CELL LA English DT Article ID ENDOTHELIAL CELL RECOGNITION; NODE HOMING RECEPTOR; L-SELECTIN; LYMPH-NODE; NEUTROPHIL ADHESION; MESENTERIC VENULES; LECAM-1; INVIVO; GLYCOPROTEIN; LYMPHOCYTES AB Leukocyte adhesion to endothelium requires specialized mechanisms for contact initiation under flow, L-selectin (CD62L), an efficient initiator of adhesion, is clustered on the tips of leukocyte microvilli. To test whether microvillous presentation is critical for contact formation (''tethering''), we transfected lymphoid cells with chimeras of L-selectin and CD44, an adhesion molecule that is excluded from microvilli, CD44 transmembrane and intracellular (TM-IC) domains targeted the L-selectin ectodomain to the planar body, whereas L-selectin TM-IC segments conferred CD44 ectodomain clustering on microvilli. Wild-type and chimeric transfectants bound similarly to anti-ectodomain MAbs in static assays, but MAb binding under Row was much more efficient in the context of microvillous presentation, Similarly, wild-type and chimeric L-selectin possessed equivalent lectin activity, but microvillous presentation dramatically enhanced contact initiation on a native ligand. These findings demonstrate a critical role for receptor topography in leukocyte adhesion and suggest a novel regulatory mechanism of leukocyte trafficking. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. STANFORD UNIV,SCH MED,DEPT PATHOL,IMMUNOL & VASC BIOL LAB,STANFORD,CA 94305. STANFORD UNIV,SCH MED,DEPT MED,CTR DIGEST DIS,STANFORD,CA 94305. VET AFFAIRS PALO ALTO HLTH CARE SYST,FOOTHILL RES CTR,CTR MOLEC BIOL & MED,PALO ALTO,CA 94304. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT DERMATOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455. RP VONANDRIAN, UH (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115, USA. RI von Andrian, Ulrich/A-5775-2008 FU NIAID NIH HHS [AI19957, AI37832]; NIGMS NIH HHS [GM37734] NR 46 TC 303 Z9 306 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 22 PY 1995 VL 82 IS 6 BP 989 EP 999 DI 10.1016/0092-8674(95)90278-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RW693 UT WOS:A1995RW69300015 PM 7553859 ER PT J AU PRIGENT, SA PILLAY, TS RAVICHANDRAN, KS GULLICK, WJ AF PRIGENT, SA PILLAY, TS RAVICHANDRAN, KS GULLICK, WJ TI BINDING OF SHC TO THE NPXY MOTIF IS MEDIATED BY ITS N-TERMINAL DOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID TYROSINE PHOSPHORYLATION; PROTEIN; RECEPTOR; KINASE; SITES AB She is an SH2-containing adapter protein that binds to and is phosphorylated by a large number of growth factor receptors, Phosphorylated She is able to interact with the GrbB-Sos complex which is responsible for mediating nucleotide exchange on Ras. We have shown previously that binding of She to the epidermal growth factor (EGF)-like receptor, c-ErbB-3, is through an NPXY motif (Prigent, S, A., and Gullick, W, J, (1994) EMBO J. 13, 2831-2841) shared by middle T antigen, TrkA, and EGF receptor, It has recently been reported that a region distinct from the SH2 domain is able to bind to tyrosine-phosphorylated proteins. In this paper we have used fusion proteins of various She domains to show that it is the N-terminal domain of She that is primarily responsible for binding EGF receptor and c-ErbB-3. Furthermore, by competition studies with synthetic phosphopeptides we have shown that this N-terminal domain binds to the previously identified NPXY motif. C1 UNIV CALIF SAN DIEGO,DIV ENDOCRINOL & METAB,LA JOLLA,CA 92093. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HAMMERSMITH HOSP,IMPERIAL CANC RES FUND,MOLEC ONCOL LAB,ONCOL UNIT,LONDON W12 0HS,ENGLAND. RP PRIGENT, SA (reprint author), UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093, USA. NR 40 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 22 PY 1995 VL 270 IS 38 BP 22097 EP 22100 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RW314 UT WOS:A1995RW31400006 PM 7673183 ER PT J AU NALEFSKI, EA SHAW, KTY RAO, A AF NALEFSKI, EA SHAW, KTY RAO, A TI AN ION-PAIR IN CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX HETERODIMERS CRITICAL FOR SURFACE EXPRESSION AND PEPTIDE PRESENTATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL RECEPTOR; ANTIGEN-BINDING SITE; MOUSE MHC ANTIGENS; A-BETA-CHAIN; INVARIANT-CHAIN; MONOCLONAL-ANTIBODIES; VIRAL PEPTIDES; INTRACELLULAR-TRANSPORT; 3-DIMENSIONAL STRUCTURE; ALPHA-CHAIN AB In this report we demonstrate that the ion pair Arg-80 alpha and Asp-57 beta, located in the peptide-binding site of nearly all class II major histocompatibility complex (MHC) proteins, is important for surface expression and function of the murine class II heterodimer I-A(d). Charge reversal at either of these two residues by site-directed mutagenesis generated mutant class Il molecules that failed to appear at the cell surface. This defect in surface expression was partially reversed when the invariant chain was present or when the mutants were paired with the corresponding charge-reversed variant of the opposite chain. Surprisingly, surface expression was restored when cells expressing the single-site mutants were cultured at reduced temperature, In addition, the substitution of Asp-57 beta with residues found in alleles of class II molecules associated with diabetes resulted in heterodimers that were inefficiently expressed at the cell surface and presented foreign peptide poorly. Together, these results demonstrate that the formation of a salt-bridge between Arg-80 alpha and Asp-57 beta is required for efficient surface expression of class II MHC molecules, therefore representing an important step in the assembly and transport of functional class II heterodimers to the cell surface. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI22900] NR 69 TC 12 Z9 12 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 22 PY 1995 VL 270 IS 38 BP 22351 EP 22360 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RW314 UT WOS:A1995RW31400046 PM 7673219 ER PT J AU HUANG, PL HUANG, ZH MASHIMO, H BLOCH, KD MOSKOWITZ, MA BEVAN, JA FISHMAN, MC AF HUANG, PL HUANG, ZH MASHIMO, H BLOCH, KD MOSKOWITZ, MA BEVAN, JA FISHMAN, MC TI HYPERTENSION IN MICE LACKING THE GENE FOR ENDOTHELIAL NITRIC-OXIDE SYNTHASE SO NATURE LA English DT Article ID NADPH DIAPHORASE; RELAXING FACTOR; BLOOD-PRESSURE; L-ARGININE; INHIBITORS; NEURONS; INVIVO; NERVE AB NITRIC oxide (NO), a potent vasodilator produced by endothelial cells, is thought to be the endothelium-dependent relaxing factor (EDRF) which mediates vascular relaxation in response to acetylcholine, bradykinin and substance P in many vascular besds(1-6). NO has been implicated in the regulation of blood pressure and regional blood flow(4-6), and also affects vascular smooth-muscle proliferation and inhibits platelet aggregation and leukocyte adhesion. Abnormalities in endothelial production of NO occur in atherosclerosis, diabetes and hypertension(7). Pharmacological blockade of NO production with arginine analogues such as L-nitroarginine (L-NA) or L-N-arginine methyl ester affects multiple isoforms of nitric oxide synthase (NOS), and so cannot distinguish their physiological roles(8,9). To study the role of endothelial NOS (eNOS) in vascular function, we disrupted the gene encoding eNOS in mice. Endothelium-derived relaxing factor activity, as assayed by acetylcholine-induced relaxation, is absent, and the eNOS mutant mice are hypertensive. Thus eNOS mediates basal vasodilation. Responses to NOS blockade in the mutant mice suggest that non-endothelial isoforms of NOS mag be involved in maintaining blood pressure. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,MED SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT NEUROL,STROKE RES LAB,BOSTON,MA 02129. UNIV VERMONT,COLL MED,DEPT PHARMACOL,BURLINGTON,VT 05405. RI Moskowitz, Michael/D-9916-2011 NR 27 TC 1449 Z9 1478 U1 4 U2 52 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 21 PY 1995 VL 377 IS 6546 BP 239 EP 242 DI 10.1038/377239a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RV872 UT WOS:A1995RV87200042 PM 7545787 ER PT J AU SHANER, A ECKMAN, TA ROBERTS, LJ WILKINS, JN TUCKER, DE TSUANG, JW MINTZ, J AF SHANER, A ECKMAN, TA ROBERTS, LJ WILKINS, JN TUCKER, DE TSUANG, JW MINTZ, J TI DISABILITY INCOME, COCAINE USE, AND REPEATED HOSPITALIZATION AMONG SCHIZOPHRENIC COCAINE ABUSERS - A GOVERNMENT-SPONSORED REVOLVING-DOOR SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ADDICTION SEVERITY INDEX; SUBSTANCE-ABUSE; DRUG-ABUSE; PSYCHIATRIC-PATIENTS; URINE; CHROMATOGRAPHY; VALIDITY AB Background. Many patients with serious mental illness are addicted to drugs and alcohol. This comorbidity creates additional problems for the patients and for the clinicians, health care systems, and social-service agencies that provide services to this population. One problem is that disability income, which many people with serious mental illness receive to pay for basic needs, may facilitate drug abuse. In this study, we assessed the temporal patterns of cocaine use, psychiatric symptoms, and psychiatric hospitalization in a sample of schizophrenic patients receiving disability income. Methods. We evaluated 105 male patients with schizophrenia and cocaine dependence at the time of their admission to the hospital. They had severe mental illness and a long-term dependence on cocaine, with repeated admissions to psychiatric hospitals; many were homeless. The severity of psychiatric symptoms and urinary concentrations of the cocaine metabolite benzoylecgonine were evaluated weekly for 15 weeks. Results. Cocaine use, psychiatric symptoms, and hospital admissions all peaked during the first week of the month, shortly after the arrival of the disability payment, on the first day. The average patient spent nearly half his total income on illegal drugs. Conclusions. Among cocaine-abusing schizophrenic persons, the cyclic pattern of drug use strongly suggests that it is influenced by the monthly receipt of disability payments. The consequences of this cycle include the depletion of funds needed for housing and food, exacerbation of psychiatric symptoms, more frequent psychiatric hospitalization, and a high rate of homelessness. The troubling irony is that income intended to compensate for the disabling effects of severe mental illness may have the opposite effect. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. RP SHANER, A (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,116A,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NIMH NIH HHS [R01 MH48081] NR 39 TC 148 Z9 148 U1 3 U2 11 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 21 PY 1995 VL 333 IS 12 BP 777 EP 783 DI 10.1056/NEJM199509213331207 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RU809 UT WOS:A1995RU80900007 PM 7643886 ER PT J AU RICHARDSON, PM ZON, LI AF RICHARDSON, PM ZON, LI TI MOLECULAR-CLONING OF A CDNA WITH A NOVEL DOMAIN PRESENT IN THE TRE-2 ONCOGENE AND THE YEAST-CELL CYCLE REGULATORS BUB2 AND CDC16 SO ONCOGENE LA English DT Article DE HEMATOPORESIS; MAST CELLS; CELL CYCLE; CDNA; GERM CELLS ID BINDING TRANSCRIPTION FACTORS; MAST-CELLS; CARBOXYPEPTIDASE-A; PROTEIN CDNA; GENE; IDENTIFICATION; SEQUENCES; CYTOKINESIS; ENCODES; MITOSIS AB Tn an effort to identify genes that are differentially regulated during mast cell development, subtracted cDNA prepared from wild-type murine P815 mastocytoma cells and a P815 subline that exhibits properties of mast cell differentiation was used to screen mast cell cDNA libraries. Several known mast cell-specific cDNAs were isolated including mast cell carboxypeptidase A (MC-CPA), murine mast cell protease-5 (MMCP-5), and gp49. A novel cDNA, designated Tbc1, was identified that showed differential expression in the two mast cell lines. The amino acid sequence predicted from the cDNA contains a 200 amino acid domain that is homologous to regions in the tre-2 oncogene and the yeast regulators of mitosis, BUB2 and cdc16. The N-terminal region contains a number of cysteine and histidine residues, potentially encoding a zinc finger domain. Tbc1 is a nuclear protein and is expressed in highest levels in hematopoietic cells, testis and kidney. Within these tissues, expression of Tbc1 is cell- and stage-specific. Based on sequence similarity, pattern of expression and subcellular localization, Tbc1 may play a role in the cell cycle and differentiation of various tissues. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. FU NHLBI NIH HHS [R01 HL46668, P10 HL32262] NR 33 TC 52 Z9 54 U1 2 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 21 PY 1995 VL 11 IS 6 BP 1139 EP 1148 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RX180 UT WOS:A1995RX18000017 PM 7566974 ER PT J AU SALGIA, R BRUNKHORST, B PISICK, E LI, JL LO, SH CHEN, LB GRIFFIN, JD AF SALGIA, R BRUNKHORST, B PISICK, E LI, JL LO, SH CHEN, LB GRIFFIN, JD TI INCREASED TYROSINE PHOSPHORYLATION OF FOCAL ADHESION PROTEINS IN MYELOID CELL-LINES EXPRESSING P210(BCR/ABL) SO ONCOGENE LA English DT Article DE P210(BCR/AB1); ACTIN; TYROSINE PHOSPHORYLATION; CYTOSKELETAL PROTEINS ID CHRONIC MYELOGENOUS LEUKEMIA; PHILADELPHIA-CHROMOSOME; KINASE; PAXILLIN; BINDING; ABL; BCR; TRANSFORMATION; FIBROBLASTS; FIBRONECTIN AB The BCR/ABL oncogene causes chronic myelogenous leukemia (CML) in humans and induces growth factor independence of hematopoietic cell lines in tissue culture. p210(BCR/ABL) is localized at least in part to the cytoskeleton, and has been shown to interact directly with actin filaments through an actin binding domain located in the C-terminus of ABL. CML cells have reduced adhesion to some extracellular matrix components but the mechanism of this phenomenon is unknown. In this study we examined tyrosine phosphorylation of focal adhesion proteins in cells expressing p210(BCR/ABL) An interleukin-3 (IL-3)-dependent cell line, 32Dc13, was transformed with a BCR/ABL cDNA, and the patterns of localization, expression, and tyrosine phosphorylation of focal adhesion proteins were compared among untransformed 32Dc13 cells with and without IL-3 stimulation and BCR/ABL-transformed 32Dc13 cells. Of the focal adhesion proteins examined, only paxillin exhibited tyrosine phosphorylation in response to IL-3; while in cells transformed by p210(BCR/ABL), paxillin, vinculin, p125(FAK), talin and tensin were constitutively tyrosine phosphorylated. IL-3 induced a transient association between paxillin and vinculin, while in BCR/ABL-transformed cells, several proteins coimmunoprecipitated with paxillin, including vinculin, p125(FAK), talin and tensin. Pseudopodia enriched in focal adhesion proteins were transiently detected in 32Dc13 cells in response to IL-3, but constitutively detected in cells expressing p210(BCR/ABL). P210(BCR/ABL) protein was also found concentrated in punctate structures adjacent to the cell membrane in myeloid cell lines, which often contained vinculin and paxillin. Since the focal adhesion is where the interaction between integrins and actin filaments is believed to occur, the observed effect of p210(BCR/ABL) on food adhesion protein interactions in myeloid cell lines could contribute to the adhesion defects in CML cells. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI Li, Jian-Liang/0000-0002-6487-081X NR 35 TC 139 Z9 140 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 21 PY 1995 VL 11 IS 6 BP 1149 EP 1155 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RX180 UT WOS:A1995RX18000018 PM 7566975 ER PT J AU REYMOND, A BRENT, R AF REYMOND, A BRENT, R TI P16 PROTEINS FROM MELANOMA-PRONE FAMILIES ARE DEFICIENT IN BINDING TO CDK4 SO ONCOGENE LA English DT Article DE P16(INK4A); CDK4; CDK6; CKI, MELANOMA; 2-HYBRIDS ID TRANSFORMATION AB The tumor suppressor candidate p16(INK4) is a cyclin-dependent kinase inhibitor that inhibits cell proliferation, The p16 coding gene is often mutated in glioblastomas, pancreatic adenocarcinomas and melanoma-prone pedigrees, but, until recently, the significance of these allelic variants has remained unclear. Here, we used interaction mating and coprecipitation to measure interaction of seven p16 allelic variants detected in melanoma-prone pedigrees with Cyclin-dependent kinases (Cdks), We found that most variants were deficient in interaction with Cdk4 and Cdk6. One defective variant was found both in cancer prone families and in the control population and therefore previously defined as a common polymorphism. Another variant, which is weakly linked to familial cancer, is only slightly affected in interaction with Cdks. These results are consistent with the idea that p16 allelic variants that decrease Cdk interaction predispose individuals who carry them to an increased risk of cancer. Moreover, they suggest that determination of affinity between p16 mutants and partner proteins may help identify functionally-significant allelic variants not detected by classical human genetic techniques. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP REYMOND, A (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 24 TC 92 Z9 92 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 21 PY 1995 VL 11 IS 6 BP 1173 EP 1178 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA RX180 UT WOS:A1995RX18000021 PM 7566978 ER PT J AU MITHOFER, K FERNANDEZDELCASTILLO, C MANDAVILLI, U RATTNER, DW WARSHAW, AL AF MITHOFER, K FERNANDEZDELCASTILLO, C MANDAVILLI, U RATTNER, DW WARSHAW, AL TI QUANTITATIVE ASSAY OF TRYPSINOGEN BY MEASUREMENT OF CLEAVED ACTIVATION PEPTIDE AFTER ACTIVATION WITH ENTEROKINASE SO ANALYTICAL BIOCHEMISTRY LA English DT Note C1 MASSACHUSETTS GEN HOSP,SURG LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 10 TC 8 Z9 8 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 20 PY 1995 VL 230 IS 2 BP 348 EP 350 DI 10.1006/abio.1995.1486 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA RW605 UT WOS:A1995RW60500023 PM 7503430 ER PT J AU JARVELA, IE MITCHISON, HM ORAWE, AM MUNROE, PB TASCHNER, PEM DEVOS, N LERNER, TJ DARIGO, KL CALLEN, DF THOMPSON, AD KNIGHT, M MARRONE, BL MUNDT, MO MEINCKE, L BREUNING, MH GARDINER, RM DOGGETT, NA MOLE, SE AF JARVELA, IE MITCHISON, HM ORAWE, AM MUNROE, PB TASCHNER, PEM DEVOS, N LERNER, TJ DARIGO, KL CALLEN, DF THOMPSON, AD KNIGHT, M MARRONE, BL MUNDT, MO MEINCKE, L BREUNING, MH GARDINER, RM DOGGETT, NA MOLE, SE TI YAC AND COSMID CONTIGS SPANNING THE BATTEN-DISEASE (CLN3) REGION AT 16P12.1-P11.2 SO GENOMICS LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; REPETITIVE DNA-SEQUENCES; HUMAN CHROMOSOME-16; INSITU HYBRIDIZATION; PHYSICAL MAP; LOCUS CLN3; GENE; LOCALIZATION; IDENTIFICATION; FRAGMENTS AB A yeast artificial chromosome (YAC) contig has been constructed in 16p12.1-p11.2 that encompasses three loci (D16S288, D16S299, and D16S298) closely linked to the gene causing fatten disease or juvenile-onset neuronal ceroid lipofuscinosis (CLN3). The physical map has been ordered using 42 sequence tagged sites. Four genes, interleukin-4 receptor (IL4R), phenol-preferring phenol sulfotransferase (STP), monoamine-preferring phenol sulfotransferase (STM), and sialophorin (SPN), have been mapped to the YAC contig. A partial genomic restriction map has been constructed to confirm the order and distances between D16S288 and STM. This part of the YAC contig is represented in eight cosmid contigs. One of these contains D16S298, predicted to be the locus closest to CLN3. The overlapping genomic clones are a valuable resource for cloning the Batten gene (CLN3) and other genes in the region. (C) 1995 Academic Press, Inc. C1 UCL, SCH MED, RAYNE INST, DEPT PAEDIAT, LONDON WC1E 6JJ, ENGLAND. LEIDEN UNIV, DEPT HUMAN GENET, SYLVIUS LAB, 2300 RA LEIDEN, NETHERLANDS. MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BOSTON, MA USA. WOMENS & CHILDRENS HOSP, DEPT CYTOGENET & MOLEC GENET, ADELAIDE, SA, AUSTRALIA. LOS ALAMOS NATL LAB, DIV LIFE SCI, LOS ALAMOS, NM USA. LOS ALAMOS NATL LAB, CTR HUMAN GENOME STUDIES, LOS ALAMOS, NM 87545 USA. RI Mitchison, Hannah/C-1891-2008; Mole, Sara/C-2024-2008; Callen, David/G-1975-2012; Jarvela, Irma/L-5836-2013; OI Callen, David/0000-0002-6189-9991; Mole, Sara/0000-0003-4385-4957; Taschner, Peter/0000-0001-9621-465X FU PHS HHS [28722, 30152, 32009]; Wellcome Trust NR 47 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 20 PY 1995 VL 29 IS 2 BP 478 EP 489 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RY055 UT WOS:A1995RY05500022 PM 8666398 ER PT J AU YONG, WH UEKI, K CHOU, D REEVES, SA VONDEIMLING, A GUSELLA, JF MOHRENWEISER, HW BUCKLER, AJ LOUIS, DN AF YONG, WH UEKI, K CHOU, D REEVES, SA VONDEIMLING, A GUSELLA, JF MOHRENWEISER, HW BUCKLER, AJ LOUIS, DN TI CLONING OF A HIGHLY CONSERVED HUMAN PROTEIN SERINE-THREONINE PHOSPHATASE GENE FROM THE GLIOMA CANDIDATE REGION ON CHROMOSOME 19Q13.3 SO GENOMICS LA English DT Note ID HUMAN ASTROCYTOMAS AB Allelic loss studies have suggested that a glioma tumor suppressor gene resides in a 425-kb region of chromosome 19q, telomeric to D19S219 and centromeric to D19S112. Exon amplification of a cosmid contig spanning this region yielded four exons with high homology to a rat protein serine-threonine phosphatase from a cosmid approximately 100 kb telomeric to D19S219. Isolation of a near full-length cDNA from a human fetal brain cDNA library revealed a protein serine-threonine phosphatase with a tetratricopeptide motif, almost identical to human PPP5C (PP5) and highly homologous to rat PPT. Northern blotting demonstrated expression in most human tissues, including brain. Primary and cultured gliomas were studied for genetic alterations in this gene using pulsed-field gel electrophoresis, routine Southern blots, and genomic DNA- and RNA-based single-strand conformation polymorphism analysis. Genomic alterations were not detected in any of the gliomas, and all studied gliomas expressed the gene, suggesting that this phosphatase is not the putative chromosome 19q glioma tumor suppresser gene. (C) 1995 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,NEUROSURG SERV,MOLEC NEUROONCOL LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV HOSP BONN,INST NEUROPATHOL,BONN,GERMANY. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA 94550. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [T32-CA90216, CA 57683] NR 19 TC 27 Z9 28 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 20 PY 1995 VL 29 IS 2 BP 533 EP 536 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RY055 UT WOS:A1995RY05500028 PM 8666404 ER PT J AU HUGHES, R CHAN, FY WHITE, RA ZON, LI AF HUGHES, R CHAN, FY WHITE, RA ZON, LI TI CLONING AND CHROMOSOMAL LOCALIZATION OF A MOUSE CDNA WITH HOMOLOGY TO THE SACCHAROMYCES-CEREVISIAE GENE ZUOTIN SO GENOMICS LA English DT Note ID LAMBDA-DNA-REPLICATION; HEAT-SHOCK PROTEIN; ESCHERICHIA-COLI; YEAST HOMOLOG; ENDOPLASMIC-RETICULUM; BACTERIOPHAGE-LAMBDA; BINDING-PROTEIN; INITIATION; TRANSLATION; EXPRESSION AB The eukaryotic DnaJ homologs form a family of proteins with diverse functions. One member of the family, the Saccharomyces cerevisiae gene zuotin, was isolated for its ability to bind Z-DNA. Here, we have isolated a mouse cDNA called ZRF1 (for zuotin-related factor 1) with significant homology to zuotin. The DnaJ domain and candidate phosphorylation sites of zuotin and ZRF1 are highly conserved. ZRF1 is expressed in all tissues, and the mouse ZRF1 gene is localized on chromosome 5. The structural similarity of zuotin and ZRF1 suggests conservation of function of this DnaJ subfamily. (C) 1995 Academic Press, Inc. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. UNIV MISSOURI,CHILDRENS MERCY HOSP,SCH MED,GENET SECT,KANSAS CITY,MO 64108. FU NHLBI NIH HHS [P01-HL32262] NR 33 TC 7 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 20 PY 1995 VL 29 IS 2 BP 546 EP 550 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RY055 UT WOS:A1995RY05500031 PM 8666407 ER PT J AU GRABAREK, Z MABUCHI, Y GERGELY, J AF GRABAREK, Z MABUCHI, Y GERGELY, J TI PROPERTIES OF TROPONIN-C ACETYLATED AT LYSINE RESIDUES SO BIOCHEMISTRY LA English DT Article ID SKELETAL-MUSCLE TROPONIN; PROTON-MAGNETIC-RESONANCE; CENTRAL HELIX MUTANTS; BIOLOGICAL-ACTIVITY; INHIBITORY REGION; PEPTIDE COMPLEX; CROSS-LINKING; CA2+ BINDING; CONFORMATIONAL TRANSITION; PROTEOLYTIC FRAGMENTS AB We have studied the properties of rabbit skeletal troponin C (TnC) fully acetylated at its lysine residues (AcTnC). Acetylation causes a decrease in thermal stability of both domains of TnC in the absence of Ca2+. At 25 degrees C, the acetylated C-terminal domain of TnC is almost completely unfolded and the melting temperature of the N-terminal domain monitored by far-UV circular dichroism is decreased by 16.3 degrees C. In the presence of 1 mM CaCl2, no cooperative unfolding can be detected up to 90 degrees C for either TnC or AcTnC. At 25 degrees C, CD spectra show that AcTnC has a slightly lower alpha-helix content in the absence of Ca2+, but higher in the presence of Ca2+ as compared to unmodified TnC. Acetylation causes a 3.5-fold increase in affinity for Ca2+ at the low-affinity sites and a 2-fold decrease at the high-affinity sites. Polyacrylamide gel electrophoresis under nondissociating conditions (no SDS, no urea, pH 8.6) indicates that acetylation has little effect on the apparent affinity of TnC for troponin I; however, the binding of the acetylated peptides corresponding to the N-terminal domain of TnC to troponin I is significantly stronger than that of the unmodified peptides. Troponin T binding to AcTnC is significantly enhanced, the altered properties of the N-terminal domain being predominantly responsible for the increase. Titration of the ATPase activity of TnC-depleted myofibrils with AcTnC or native TnC indicates that acetylation increases TnC's affinity for myofibrils in the presence of Ca2+ similar to 6 times; at saturation the ATPase activity is the same for the two forms of TnC. The Ca2+ dependence of the ATPase activity of myofibrils containing AcTnC is shifted to lower Ca2+ concentrations, consistent with the higher Ca2+ affinity of AcTnC at the low-affinity sites. These data indicate that positively charged lysine side chains, especially those located in the N-terminal domain, modulate TnC's structural stability and interactions with Ca2+ and other troponin components. C1 MASSACHUSETTS GEN HOSP,BOSTON BIOMED RES INST,NEUROL SERV,MUSCLE RES GRP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. OI Grabarek, Zenon/0000-0002-3636-5701 FU NHLBI NIH HHS [R37-HL-05949]; NIAMS NIH HHS [AR-41156] NR 68 TC 14 Z9 14 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 19 PY 1995 VL 34 IS 37 BP 11872 EP 11881 DI 10.1021/bi00037a027 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RX003 UT WOS:A1995RX00300027 PM 7547922 ER PT J AU GAZIT, Y BERK, DA LEUNIG, M BAXTER, LT JAIN, RK AF GAZIT, Y BERK, DA LEUNIG, M BAXTER, LT JAIN, RK TI SCALE-INVARIANT BEHAVIOR AND VASCULAR NETWORK FORMATION IN NORMAL AND TUMOR-TISSUE SO PHYSICAL REVIEW LETTERS LA English DT Article ID MICROVASCULAR ARCHITECTURE; RETINAL-VESSELS; GROWTH-FACTOR; ANGIOGENESIS AB Tumor vascular networks look different from normal vascular networks, but the mechanisms underlying these differences are not known. By studying the scale-invariant behavior of normal and tumor vascular networks we show that vascular networks exhibit three classes of fractal behavior. Tumor networks display percolationlike scaling. Normal arteriovenous networks display diffusion-limited scaling, and normal capillary networks are compact structures. The mechanisms responsible for these differences are suggested using a growth model. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114. RP GAZIT, Y (reprint author), HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139, USA. RI Berk, David/A-4863-2012; Leunig, Michael/E-7951-2017 OI Berk, David/0000-0002-3855-6886; Leunig, Michael/0000-0002-2036-5416 NR 22 TC 126 Z9 134 U1 1 U2 15 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD SEP 18 PY 1995 VL 75 IS 12 BP 2428 EP 2431 DI 10.1103/PhysRevLett.75.2428 PG 4 WC Physics, Multidisciplinary SC Physics GA RU811 UT WOS:A1995RU81100044 ER PT J AU MCLAUGHLIN, JT HAWROT, E YELLEN, G AF MCLAUGHLIN, JT HAWROT, E YELLEN, G TI COVALENT MODIFICATION OF ENGINEERED CYSTEINES IN THE NICOTINIC ACETYLCHOLINE-RECEPTOR AGONIST-BINDING DOMAIN INHIBITS RECEPTOR ACTIVATION SO BIOCHEMICAL JOURNAL LA English DT Article ID SITE-DIRECTED MUTAGENESIS; ALPHA-SUBUNIT; SENSORY RECEPTOR; LIGAND-BINDING; DELTA-SUBUNIT; AMINO-ACIDS; IDENTIFICATION; RESIDUES; AFFINITY; MUTANTS AB We constructed and characterized a series of nicotinic receptor mutants with a cysteine substituted for one of the amino acid residues in the alpha-subunit between positions 183 and 198. This region of the receptor is known to participate in agonist binding and channel activation. The goal of this 'cysteine scanning mutagenesis' is to introduce the reactivity of a free thiol group into functionally important protein domains; modification of the introduced cysteines can then be used to probe the structure and function of the targeted region. Mutants were examined by coexpression with the beta-, gamma- and delta-subunits in Xenopus oocytes using two-microelectrode voltage clamp recording. Twelve of fourteen mutants expressed receptors with properties comparable with the wild-type, including sensitivity to reduction by dithiothreitol (DTT). This indicates that introduction of an additional cysteine within this region of the receptor did not interfere with formation of the native disulphide between alpha Cys-192 and alpha Cys-193. Only one mutation, alpha Y198C, caused dramatic changes in the EC(50) for acetylcholine (ACh) and in the sensitivity to DTT. We then examined the effects of the thiol modification and found two mutants, alpha H186C and alpha V188C, that showed significant decreases in responsiveness to ACh after exposure to methyl-methanethiosulphonate (MMTS). Dose-response measurements show that exposure of alpha H186C mutants to MMTS causes a shift in apparent agonist affinity without changing the peak response, and this is not reversible by DTT. In contrast, the MMTS-treated alpha V188C mutants show changes in both apparent affinity and peak response which are readily reversed by DTT. Together, our data show that these two nearby residues occupy markedly different environments relative to the contact points for ACh. They also demonstrate that cysteine-substitution mutagenesis can be successfully applied to protein domains that include functionally important disulphides. C1 BROWN UNIV,DIV BIOL & MED,MOLEC & BIOCHEM PHARMACOL SECT,PROVIDENCE,RI 02912. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROBIOL,MOLEC PHYSIOL LAB,BOSTON,MA 02114. RP MCLAUGHLIN, JT (reprint author), TUFTS UNIV,DEPT PHARMACOL,136 HARRISON AVE,BOSTON,MA 02111, USA. OI Yellen, Gary/0000-0003-4228-7866 NR 31 TC 22 Z9 22 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 15 PY 1995 VL 310 BP 765 EP 769 PN 3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RW147 UT WOS:A1995RW14700006 PM 7575408 ER PT J AU KINASHI, T ESCOBEDO, JA WILLIAMS, LT TAKATSU, K SPRINGER, TA AF KINASHI, T ESCOBEDO, JA WILLIAMS, LT TAKATSU, K SPRINGER, TA TI RECEPTOR TYROSINE KINASE STIMULATES CELL-MATRIX ADHESION BY PHOSPHATIDYLINOSITOL-3 KINASE AND PHOSPHOLIPASE C-GAMMA-1 PATHWAYS SO BLOOD LA English DT Note ID GROWTH-FACTOR RECEPTOR; DIFFERENT SIGNALING PATHWAYS; PDGF RECEPTOR; GENE-TRANSFER; C-GAMMA; ACTIVATION; PROTEIN; AUTOPHOSPHORYLATION; MOLECULES; LINE AB Receptor tyrosine kinases are known to be important in growth and differentiation, We have recently found that c-kit, the tyrosine kinase receptor for steel factor, also regulates cell-matrix adhesion. Because Steel factor helps regulate cell migration and localization, this may be an important biologic function. Integrin adhesiveness is regulated within minutes by c-kit. The signaling pathways for tyrosine kinase stimulation of integrin adhesiveness and their relation to pathways that regulate growth and differentiation over much longer time periods remain uncharacterized, We have studied the effector pathways by which receptor tyrosine kinases regulate cell-matrix adhesion using wild-type and mutant forms of the platelet-derived growth factor (PDGF) receptor, which is closely related to c-kit. The PDGF receptor expressed in mast cells is as potent as c-kif in stimulating adhesion to fibronectin. We show that induction of adhesion is regulated through two independent pathways of phosphatidylinositol 3 kinase (Pl3K) and phospholipase C-gamma 1 (PLC gamma)-protein kinase C by elimination of autophosphorylation sites required for activation of Pl3K and PLC gamma or in combination with downregulation of protein kinase C or wortmannin, By contrast, a receptor mutated in both the Pl3K and PLC gamma association sites can still stimulate mast cell growth, indicating a crucial role of these effector molecules in regulating adhesion rather than cell growth, (C) 1995 by The American Society of Hematology. C1 UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. HARVARD UNIV,SCH MED,BOSTON,MA. CTR BLOOD RES,BOSTON,MA 02115. RP KINASHI, T (reprint author), UNIV TOKYO,INST MED SCI,DEPT IMMUNOL,MINATO KU,4-6-1 SHIROKUNEDAI,TOKYO 108,JAPAN. FU NIDDK NIH HHS [DK45104] NR 25 TC 92 Z9 93 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1995 VL 86 IS 6 BP 2086 EP 2090 PG 5 WC Hematology SC Hematology GA RU052 UT WOS:A1995RU05200004 PM 7545020 ER PT J AU REMOLDODONNELL, E PARENT, D AF REMOLDODONNELL, E PARENT, D TI SPECIFIC SENSITIVITY OF CD43 TO NEUTROPHIL ELASTASE SO BLOOD LA English DT Article ID WISKOTT-ALDRICH SYNDROME; CELL-SURFACE EXPRESSION; SIALOPHORIN CD43; MONOCLONAL-ANTIBODY; CATHEPSIN-G; SUBCELLULAR-LOCALIZATION; LEUKOCYTE ELASTASE; ADHESION; ACTIVATION; ANTIGEN AB CD43 (sialophorin, leukosialin), an O-glycosylated and sialylated membrane protein (surface sialomucin) with antiadhesive properties, is thought to protect circulating leukocytes by preventing cell surface interactions. Although it is resistant to several proteases, the granule enzyme elastase was recently implicated in loss of extracellular CD43 regions from incubated neutrophils. Flow cytometry showed that neutrophil CD43 is cleaved by low levels of neutrophil elastase with half-maximal cleavage at 5 mu g/mL; pancreatic elastase, in contrast, did not cleave CD43, Related neutrophil granule proteases proteinase-3 and cathepsin-G did not cleave CD43 or required greater than 10-fold higher enzyme levels, respectively. The 115-kD CD43 isoform on T-lymphoid cells, which differs in glycosylation from 135-kD neutrophil CD43, was equally sensitive to neutrophil elastase, suggesting that cleavage susceptibility extends to various leukocytes. Enzymatic removal of sialic acid did not facilitate CD43 cleavage by neutrophil elastase, a feature that distinguishes the action of neutrophil elastase from other proteases. Western blots of elastase-treated neutrophils detected an 83-kD CD43 fragment that, together with the released 52-kD fragment and 40-kD subfragment, accounts for the entire molecule and indicates that CD43 is cleaved at two sites only, releasing the distal approximate to 40% of the sialomucin region. The specificity of the CD43 cleaving reaction was shown by the insensitivity of other neutrophil and lymphoid surface proteins to elastase levels that deplete CD43. Exceptions were P-selectin glycoprotein ligand-1 on neutrophils, also a surface mucin, and CD16 (Fc gamma RIII), which was previously characterized as elastase sensitive. The sensitivity and specificity of CD43 cleavage by neutrophil elastase, the very high levels of elastase in human neutrophils and its ready release by stimulating conditions suggest important physiologic/pathologic roles for this CD43 cleaving reaction. (C) 1995 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP REMOLDODONNELL, E (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI29880] NR 63 TC 30 Z9 30 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1995 VL 86 IS 6 BP 2395 EP 2402 PG 8 WC Hematology SC Hematology GA RU052 UT WOS:A1995RU05200041 PM 7662987 ER PT J AU SYKES, M SZOT, GL NGUYEN, PL PEARSON, DA AF SYKES, M SZOT, GL NGUYEN, PL PEARSON, DA TI INTERLEUKIN-12 INHIBITS MURINE GRAFT-VERSUS-HOST DISEASE SO BLOOD LA English DT Article ID CELL STIMULATORY FACTOR; BONE-MARROW TRANSPLANTATION; INTERFERON-GAMMA-PRODUCTION; TOXIC T-CELLS; IFN-GAMMA; MONOCLONAL-ANTIBODY; PERIPHERAL TOLERANCE; CYTOTOXIC ACTIVITY; IL-12; LEUKEMIA AB Interleukin-12 (IL-12) is a potent immunostimulatory cytokine and an inducer of type-1 T-helper cell activity and of cytotoxic T lymphocyte and natural killer cell function. We report here the paradoxical observation that a single injection of 4,900 IU of recombinant murine IL-12 inhibits acute graft-versus-host disease (GVHD) in a fully major histocompatibility complex (MHC) plus multiple minor antigen-mismatched bone marrow transplantation (BMT) model (A/J --> B10). The protective effect was enhanced by administration of T-cell-depleted host-type BM cells, and complete donor-type lymphohematopoietic reconstitution was observed in most animals. Treatment with a protective course of IL-12 led to increased serum interferon-gamma (IFN-gamma) levels as compared with those for GVHD controls at early time points, when IFN-gamma was produced predominantly by host-type natural killer cells, but led to almost complete inhibition of the later GVHD-associated increase in serum IFN-gamma levels, when IFN-gamma is produced predominantly by CD4(+) T cells. Furthermore, IL-12 treatment was associated with marked alterations in the kinetics of donor T-cell expansion. Reductions in donor CD4(+) and CD8(+) T cells were observed in the spleen on day 4 post-BMT, but a marked increase in donor CD8(+) cells was observed on day 7. Unlike broadly immunosuppressive methods for inhibiting GVHD, which are associated with loss of antileukemic effects, IL-12 has the potential to mediate antileukemic effects of its own;therefore,the GVHD-inhibitory effects of IL-12 described here suggest a potential application for this cytokine in clinical BMT. (C) 1995 by The American Society of Hematology. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02129. RP SYKES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,SURG SERV,MGH-E,BOSTON,MA 02129, USA. FU NCI NIH HHS [R01CA9225]; NIAID NIH HHS [R01AI31158] NR 62 TC 102 Z9 102 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1995 VL 86 IS 6 BP 2429 EP 2438 PG 10 WC Hematology SC Hematology GA RU052 UT WOS:A1995RU05200045 PM 7662991 ER PT J AU PANDEY, P KHARBANDA, S KUFE, D AF PANDEY, P KHARBANDA, S KUFE, D TI ASSOCIATION OF THE DF3/MUC1 BREAST-CANCER ANTIGEN WITH GRB2 AND THE SOS/RAS EXCHANGE PROTEIN SO CANCER RESEARCH LA English DT Note ID CARCINOMA-ASSOCIATED ANTIGEN; EPITHELIAL TUMOR-ANTIGEN; MONOCLONAL-ANTIBODY DF3; SH3 DOMAINS; TYROSINE KINASES; TANDEM REPEATS; CDNA; GENE; MUCIN; RAS AB The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in human breast carcinomas. Although the precise functional role of this protein remains unclear, the cytoplasmic tail contains potential tyrosine phosphorylation sites for binding to Src homology 2 (SH2) domains. In the present studies using human MCF-7 breast cancer cells, we show that tyrosine phosphorylated DF3 directly interacts with the SH2 domain of the adaptor protein Grb2. The findings indicate that a pYTNP site in DF3 is responsible for this interaction. The results also demonstrate that the DF3/Grb2 complex associates with the guanine nucleotide exchange protein Sos. Because Sos binds to the SH3 domains of Grb2 and, thereby, associates with Ras at the cell membrane, formation of a DF3/Grb2/Sos complex supports a role for DF3 in intracellular signaling. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA58203] NR 36 TC 161 Z9 169 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1995 VL 55 IS 18 BP 4000 EP 4003 PG 4 WC Oncology SC Oncology GA RV099 UT WOS:A1995RV09900013 PM 7664271 ER PT J AU ANDERSON, IC SUGARBAKER, DJ GANJU, RK TSARWHAS, DG RICHARDS, WG SUNDAY, M KOBZIK, L SHIPP, MA AF ANDERSON, IC SUGARBAKER, DJ GANJU, RK TSARWHAS, DG RICHARDS, WG SUNDAY, M KOBZIK, L SHIPP, MA TI STROMELYSIN-3 IS OVEREXPRESSED BY STROMAL ELEMENTS IN PRIMARY NON-SMALL-CELL LUNG CANCERS AND REGULATED BY RETINOIC ACID IN PULMONARY FIBROBLASTS SO CANCER RESEARCH LA English DT Article ID NEGATIVE REGULATION; GENE-EXPRESSION; BREAST; CARCINOMAS; METALLOPROTEINASE; INVASION AB Stromelysin-3 (STR-3) is a recently characterized matrix metalloproteinase (MMP) that was cloned on the basis of differential expression in benign and malignant breast tumors. This MMP has a unique processing mechanism and substrate specificity. Unlike previously characterized MMPs that are secreted as inactive zymogens, STR-3 is processed within the constitutive secretory pathway and secreted as an active enzyme. Although STR-3 has a characteristic MMP structure, the enzyme does not hydrolyze many of the extracellular matrix components that are substrates for other MMPs. However, STR-3 cleaves certain serine protease inhibitors (serpins), including the alpha 1 proteinase inhibitor (alpha 1 anti-trypsin). Because alpha 1 proteinase inhibitor deficiency has a known pathogenetic role in pulmonary disease, the role of STR-3 in non-small cell lung carcinomas (NSCLC) is of great interest. STR-3 transcripts and protein were significantly more abundant in primary NSCLC than in adjacent normal lung specimens in an extensive panel of stage I-III squamous cell and adenocarcinomas. The major form of STR-3 detectable in the primary NSCLC was the mature fully processed active enzyme. STR-3 transcripts and protein were primarily localized to NSCLC stromal elements, prompting analysis of STR-3 induction in normal pulmonary fibroblasts. Although STR-3 could be induced in normal pulmonary fibroblasts with growth factors (basic fibroblast growth factor and platelet-derived growth factor) and/or 12-O-tetradecanoylphorbol-13-acetate, STR-3 induction was inhibited by all-trans retinoic acid, a commonly used chemopreventive agent for aerodigestive tract malignancies. Taken together, these data suggest that STR-3 may be a novel marker and potential therapeutic target in NSCLC. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV THORAC SURG,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 33 TC 74 Z9 74 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1995 VL 55 IS 18 BP 4120 EP 4126 PG 7 WC Oncology SC Oncology GA RV099 UT WOS:A1995RV09900033 PM 7664289 ER PT J AU OGARA, PT DESANCTIS, RW AF OGARA, PT DESANCTIS, RW TI ACUTE AORTIC DISSECTION AND ITS VARIANTS - TOWARD A COMMON DIAGNOSTIC AND THERAPEUTIC APPROACH SO CIRCULATION LA English DT Editorial Material DE EDITORIALS; AORTIC DISSECTION ID PENETRATING ATHEROSCLEROTIC ULCERS; THORACIC AORTA; INTIMAL RUPTURE; MANAGEMENT; ANEURYSMS; SURVIVAL; CT C1 MASSACHUSETTS GEN HOSP,MED SERV,CARDIAC UNIT,BOSTON,MA 02114. RP OGARA, PT (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOVASC,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 35 TC 91 Z9 96 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 15 PY 1995 VL 92 IS 6 BP 1376 EP 1378 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RU672 UT WOS:A1995RU67200002 PM 7664413 ER PT J AU SHAH, PK FALK, E BADIMON, JJ FERNANDEZORTIZ, A MAILHAC, A VILLAREALLEVY, G FALLON, JT REGNSTROM, J FUSTER, V AF SHAH, PK FALK, E BADIMON, JJ FERNANDEZORTIZ, A MAILHAC, A VILLAREALLEVY, G FALLON, JT REGNSTROM, J FUSTER, V TI HUMAN MONOCYTE-DERIVED MACROPHAGES INDUCE COLLAGEN BREAKDOWN IN FIBROUS CAPS OF ATHEROSCLEROTIC PLAQUES - POTENTIAL ROLE OF MATRIX-DEGRADING METALLOPROTEINASES AND IMPLICATIONS FOR PLAQUE RUPTURE SO CIRCULATION LA English DT Article; Proceedings Paper CT 66th Scientific Session of the American-Heart-Association CY NOV 08-11, 1993 CL ATLANTA, GA SP Amer Heart Assoc DE MACROPHAGES; METALLOPROTEINASES; PLAQUE ID HUMAN MONONUCLEAR PHAGOCYTES; STROMELYSIN GENE-EXPRESSION; ACUTE CORONARY SYNDROMES; INTERSTITIAL COLLAGENASE; PROTEINASES; THROMBOSIS; MECHANISMS; MEDIATORS AB Background Rupture of the fibrous cap of the atherosclerotic plaque is a key event that predisposes to coronary thrombosis, leading to acute coronary syndromes. Recent studies have shown that the fibrous caps of vulnerable and ruptured atherosclerotic plaques have reduced collagen and glycosaminoglycan content in association with an increased macrophage density and a reduced smooth muscle cell density. Since collagen breakdown in the fibrous caps may contribute to a thinning and weakening of the cap, increasing its vulnerability to rupture, we tested the hypothesis that monocyte-derived macrophages, by producing matrix-degrading metalloproteinases (MMPs), could induce collagen breakdown in human atherosclerotic fibrous caps. Methods and Results Monocytes were isolated from human blood by Ficoll-Paque density gradient and allowed to grow in cell culture until phenotypic and staining characteristics indicated transformation into macrophages (4 to 7 days). Fibrous caps were dissected from human aortic or carotid plaques and incubated for 48 hours with macrophages in serum-free medium without (n=21) and with (n=10) an MMP inhibitor or with cell- and serum-free medium only (n=9). Hydroxyproline released in the culture medium was measured by a spectrophotometric method and used as evidence of collagen breakdown in the fibrous caps. Immunocytochemistry with specific monoclonal antibodies was used to identify expression of MMP-1 (interstitial collagenase) and MMP-2 (72-kD gelatinase) in cell culture, and zymography was used to detect MMP activity in the culture supernatant. The amount of hydroxyproline released was significantly greater when fibrous caps were incubated with macrophages than when incubated with cell-free medium (0.4+/-0.16 mu g . mL(-1). min(-1) versus 0.02+/-0.03 mu g . mL(-1). mg(-1) of tissue; P<.04 by Mann-Whitney test). There was no hydroxyproline release when fibrous caps were incubated with macrophages in the presence of an MMP inhibitor. Immunocytochemistry demonstrated MMP-1 and MMP-2 expression by macrophages between days 4 and 7, and zymography confirmed the presence of MMP-2 activity in the supernatant. Conclusions In this study, human monocyte-derived macrophages were shown to induce collagen breakdown in fibrous caps of human atherosclerotic plaques associated with cellular expression and zymographic evidence of MMP activity; no evidence of collagen breakdown was found in the presence of an MMP inhibitor. These findings support the hypothesis that increased macrophage density and/or activation in the atherosclerotic plaque may induce collagen breakdown in the fibrous cap by secreting MMPs and possibly other proteases, thus contributing to vulnerability to plaque rupture. C1 CEDARS SINAI MED CTR,DEPT MED,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. MASSACHUSETTS GEN HOSP,CARDIOVASC BIOL RES LAB,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP SHAH, PK (reprint author), CEDARS SINAI MED CTR,ATHEROSCLEROSIS RES CTR,DIV CARDIOL,ROOM 5314,8700 BEVERLY BLVD,LOS ANGELES,CA 90077, USA. RI Falk, Erling/A-7475-2015; Fuster, Valentin/H-4319-2015; Fernandez-Ortiz, Antonio/B-2227-2017 OI Falk, Erling/0000-0001-8566-9974; Fuster, Valentin/0000-0002-9043-9986; Fernandez-Ortiz, Antonio/0000-0002-3239-1910 NR 33 TC 509 Z9 551 U1 2 U2 16 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 15 PY 1995 VL 92 IS 6 BP 1565 EP 1569 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RU672 UT WOS:A1995RU67200030 PM 7664441 ER PT J AU CALAUTTI, E MISSERO, C STEIN, PL EZZELL, RM DOTTO, GP AF CALAUTTI, E MISSERO, C STEIN, PL EZZELL, RM DOTTO, GP TI FYN TYROSINE KINASE IS INVOLVED IN KERATINOCYTE DIFFERENTIATION CONTROL SO GENES & DEVELOPMENT LA English DT Article DE FYN TYROSINE KINASE; CALCIUM; TPA; KERATINOCYTE DIFFERENTIATION; CORTACTIN ID MOUSE EPIDERMAL-CELLS; MIDDLE-T ANTIGEN; C-SRC; TERMINAL DIFFERENTIATION; MONOCLONAL-ANTIBODIES; PROTEIN-KINASES; CALCIUM REGULATION; MUTANT MICE; PHOSPHORYLATION; EXPRESSION AB Induction of tyrosine phosphorylation is an early and specific event which is required for mouse keratinocyte differentiation to occur, in response to both calcium and TPA (12-O-tetradecanoylphorbol-13-acetate). We report here that there is an increase of tyrosine kinase activity immunoprecipitable with anti-phospho tyrosine antibodies specifically in response to calcium-and a number of other divalent cations-within 2 min of exposure. Such an activity does not correspond to any of the known tyrosine kinases that were tested. A second tyrosine kinase activity is induced in response to both calcium and TPA, and has been identified as fyn, a nonreceptor tyrosine kinase of the src family. fyn activation is induced in keratinocytes within 6 hr of calcium exposure, but already within 2 min of TPA treatment. Cortactin, a p80-85 substrate of src- and fyn-related kinases that localizes with actin at cell adhesion sites, is increasingly tyrosine phosphorylated in calcium- and TPA-induced differentiation, with a time course which parallels that of fyn activation. Keratinocytes with a specific disruption of the fyn, but not yes kinase gene show no induction of phosphorylation of p80-85 proteins, and are significantly altered in their differentiation response both in vitro and in vivo. Thus, at least two tyrosine kinase activities are induced in keratinocyte differentiation, one of which has been identified as fyn and shown to be specifically involved in this process. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,SURG RES UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV TURIN,DEPT GENET BIOL & MED CHEM,TURIN,ITALY. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. OI CALAUTTI, Vincenzo/0000-0002-4439-9709 FU NCI NIH HHS [CA16038]; NIAMS NIH HHS [AR39190] NR 55 TC 98 Z9 102 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 15 PY 1995 VL 9 IS 18 BP 2279 EP 2291 DI 10.1101/gad.9.18.2279 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA RW877 UT WOS:A1995RW87700007 PM 7557381 ER PT J AU IVESTER, CT TUXWORTH, WJ COOPER, G MCDERMOTT, PJ AF IVESTER, CT TUXWORTH, WJ COOPER, G MCDERMOTT, PJ TI CONTRACTION ACCELERATES MYOSIN HEAVY-CHAIN SYNTHESIS RATES IN ADULT CARDIOCYTES BY AN INCREASE IN THE RATE OF TRANSLATIONAL INITIATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AORTIC PERFUSION-PRESSURE; PROTEIN-SYNTHESIS; CARDIAC-HYPERTROPHY; GENE-EXPRESSION; FELINE CARDIOCYTES; SKELETAL-MUSCLE; LOAD REGULATION; MESSENGER-RNAS; HEART-CELLS; OVERLOAD AB The purpose of this study was to determine the mechanism by which contraction acutely accelerates the synthesis rate of the contractile protein myosin heavy chain (MHC). Laminin-adherent adult feline cardiocytes were maintained in a serum-free medium and induced to contract at 1 Hz via electrical field stimulation. Electrical stimulation of contraction accelerated rates of MHC synthesis 28%, p < 0.05 by 4 h as determined by incorporation of [H-3]phenylalanine into MHC. MHC mRNA expression as measured by RNase protection was unchanged after 4 h of electrical stimulation. MHC mRNA levels in messenger ribonucleoprotein complexes and translating polysomes were examined by sucrose gradient fractionation. The relative percentage of polysome-bound MHC mRNA was equal at 47% in both electrically stimulated and control cardiocytes. However, electrical stimulation of contraction resulted in a reproducible shift of MHC mRNA from smaller polysomes into larger polysomes, indicating an increased rate of initiation. This shift resulted in significant increases in MHC mRNA levels in the fractions containing the larger polysomes of electrically stimulated cardiocytes as compared with nonstimulated controls. These data indicate that the rate of MHC synthesis is accelerated in contracting cardiocytes via an increase in translational efficiency. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CARDIOL SECT,CHARLESTON,SC 29401. MED UNIV S CAROLINA,GAZES CARDIAC RES INST,DEPT MED,CHARLESTON,SC 29401. MED UNIV S CAROLINA,GAZES CARDIAC RES INST,DEPT PHYSIOL,CHARLESTON,SC 29401. MED UNIV S CAROLINA,GAZES CARDIAC RES INST,DEPT CELL BIOL & ANAT,CHARLESTON,SC 29401. FU NHLBI NIH HHS [P01 HL48788-01] NR 41 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 1995 VL 270 IS 37 BP 21950 EP 21957 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU757 UT WOS:A1995RU75700080 PM 7665617 ER PT J AU SATO, T TACHIBANA, K NOJIMA, Y DAVIRRO, N MORIMOTO, C AF SATO, T TACHIBANA, K NOJIMA, Y DAVIRRO, N MORIMOTO, C TI ROLE OF THE VLA-4 MOLECULE IN T-CELL COSTIMULATION - IDENTIFICATION OF THE TYROSINE PHOSPHORYLATION PATTERN INDUCED BY THE LIGATION OF VLA-4 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOCAL ADHESION KINASE; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; INTEGRIN VLA-4; LYMPHOCYTES-T; CD4 CELLS; PROTEIN; FIBRONECTIN; ACTIVATION; INVOLVEMENT AB The very late activated Ag (VLA) molecules not only mediate T cell adhesions, but also provide costimulation in a TCR/CD3-dependent manner. However, little is known about the signals mediated by the ligation of VLA molecules. Previous work from our laboratory identified a 105-kDa protein that is predominantly phosphorylated on tyrosine residue upon engagement of VLA-4 in a human T lymphoblastic cell line, H9, and in peripheral T cells. In the present study, we have shown that the A and B epitope of VLA-4 plays a key role in VLA-4-mediated T cell costimulation. Moreover, we have demonstrated that the solid phase cross-linking of VLA-LF using Ab (against A and B) or the CS-1 region of fibronectin, stimulated tyrosine phosphorylation of 140-, 120-, 80- to 70-, 60- to 55-, 50-, and 45-kDa proteins in addition to the 105-kDa protein. In contrast, Ab ligation of the C epitope of VLA-4 mainly induced tyrosine phosphorylation of pp105, weakly induced other protein tyrosine phosphorylation, and additionally induced only minimal T cell costimulation. Using immunoblotting, we have identified some of the tyrosine-phosphorylated proteins to be phospholipase C gamma (pp140), pp125 focal adhesion kinase (pp120), paxillin (pp70 and pp50), p59(fyn)/p56(lck) (pp60-55), and mitogen-activated protein kinase (pp45). Since solid phase crosslinking of VLA-4 by B2 epitope-specific Ab induced T cell costimulation most strongly via the CD3 pathway, our results suggested that the above tyrosine-phosphorylated proteins may play an important role in VLA-4-mediated T cell costimulatory signaling events. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI-29530]; NIAMS NIH HHS [AR-33713] NR 56 TC 95 Z9 96 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1995 VL 155 IS 6 BP 2938 EP 2947 PG 10 WC Immunology SC Immunology GA RU050 UT WOS:A1995RU05000017 PM 7673711 ER PT J AU DANG, H GEISER, AG LETTERIO, JJ NAKABAYASHI, T KONG, LP FERNANDES, G TALAL, N AF DANG, H GEISER, AG LETTERIO, JJ NAKABAYASHI, T KONG, LP FERNANDES, G TALAL, N TI SLE-LIKE AUTOANTIBODIES AND SJOGRENS SYNDROME-LIKE LYMPHOPROLIFERATION IN TGF-BETA KNOCKOUT MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CELL-PROLIFERATION; LYMPHOCYTES-B; FACTOR-BETA-1; EXPRESSION; DISEASE; MOUSE; DEATH AB Mice bearing the TGF-beta 1 null mutation (-/-) develop lymphoid infiltrates in the heart, lungs, salivary glands, and other organs similar to those seen in the pseudolymphoma of Sjogren's Syndrome. We studied sera from -/- mice and found elevated Ab levels to dsDNA, ssDNA, and Sm ribonucleoprotein. No Abs to SSA/Ro or SSB/La and no IgM rheumatoid factor were found. Serum autoantibodies were predominately Ige and were specific as shown by ELISA inhibition studies. Antinuclear Ab patterns on Western blots varied from one mouse to the next, indicating a random process responsible for the diversity. Wild-type and heterozygote mice had no autoantibodies. Ig glomerular deposits were found in -/- mice, indicating that these autoantibodies may be pathogenic. Treatment of -/- mice with dexamethasone or TGF-beta 1 failed to suppress autoantibody production. These mice represent an overlap combining the autoimmune serology of SLE with the tissue infiltrates of SS. Our results support the concept that TGF-beta 1 is an important naturally occurring immunosuppressive cytokine whose absence can lead to a systemic autoimmune disease. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET HOSP,SAN ANTONIO,TX 78284. RP DANG, H (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [AG10531]; NIDCR NIH HHS [DE09311, DE10863] NR 32 TC 137 Z9 139 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1995 VL 155 IS 6 BP 3205 EP 3212 PG 8 WC Immunology SC Immunology GA RU050 UT WOS:A1995RU05000044 PM 7673733 ER PT J AU WYRICK, SD BOOTH, RG MYERS, AM OWENS, CE BUCHOLTZ, EC HOOPER, PC KULA, NS BALDESSARINI, RJ MAILMAN, RB AF WYRICK, SD BOOTH, RG MYERS, AM OWENS, CE BUCHOLTZ, EC HOOPER, PC KULA, NS BALDESSARINI, RJ MAILMAN, RB TI 1-PHENYL-3-AMINO-1,2,3,4-TETRAHYDRONAPHTHALENES AND RELATED DERIVATIVES AS LIGANDS FOR THE NEUROMODULATORY SIGMA(3) RECEPTOR - FURTHER STRUCTURE-ACTIVITY-RELATIONSHIPS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID RAT STRIATAL TISSUE; BINDING-SITES; CORPUS STRIATUM; BRAIN AB A series of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes (1-phenyl-3-aminotetralins, PATs) previously was found to stimulate tyrosine hydroxylase activity and dopamine synthesis in rat brain through interaction with a novel sigma(3) receptor. Specifically, the trans-1R,3S-(-) isomer of H-2-PAT showed highest affinity for sigma(3) receptors and also produced maximal stimulation of tyrosine hydroxylase activity and dopamine synthesis, as compared to the trans-1S,3R-(+) isomer. Affinity for sigma(3) receptors and functional potency at stimulating dopamine synthesis were attenuated either by altering the position or dimethyl substitution pattern of the amino group or by hydroxylating the tetralin aromatic ring. A preliminary binding model can accommodate many PAT analogs and several non-PATs with a wide range of affinities for the sigma(3) receptor. Here, we report the synthesis and evaluation of additional analogs in order to expand previous structure-activity relationship studies. Further molecular modifications include synthesis of 1-phenyl-1-methyl-3-amino, 1-phenyl-2-amino, 1-phenyl-3-(trimethylammoniumyl), and 1-phenyl-3-(phenylalkyl) analogs, as well as ring-expanded tetrahydrobenzocycloheptenes. In general, the above modifications decreased sigma(3) receptor affinity and, in some cases, caused a reversal of the sigma(3) binding selectivity of trans- versus cis-PATs found previously. Most analogs were selective for sigma(3) receptors and showed little or no affinity for either sigma(1)/sigma(2) or dopamine D-1, D-2, and D-3 receptors. N-Phenylalkyl substituents, such as N-phenylethyl, however, endowed the 1-phenyl-3-aminotetralins with enhanced sigma(1)/sigma(2) and dopamine receptor affinity while decreasing sigma(3) affinity, thus abolishing sigma(3) selectivity. C1 UNIV N CAROLINA,BRAIN & DEV RES CTR,CHAPEL HILL,NC 27599. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BELMONT,MA 02178. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA 02178. RP WYRICK, SD (reprint author), UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,CB 7360,CHAPEL HILL,NC 27599, USA. FU NIMH NIH HHS [MH-47370, MH-31154, MH-34006] NR 33 TC 21 Z9 21 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 15 PY 1995 VL 38 IS 19 BP 3857 EP 3864 DI 10.1021/jm00019a016 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA RW117 UT WOS:A1995RW11700016 PM 7562917 ER PT J AU WANG, MG SZEBENI, J PEARSON, DA SZOT, GL SYKES, M AF WANG, MG SZEBENI, J PEARSON, DA SZOT, GL SYKES, M TI INHIBITION OF GRAFT-VERSUS-HOST DISEASE BY INTERLEUKIN-2 TREATMENT IS ASSOCIATED WITH ALTERED CYTOKINE PRODUCTION BY EXPANDED GRAFT-VERSUS-HOST-REACTIVE CD4(+) HELPER-CELLS SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; NATURAL-KILLER-CELLS; T-CELLS; MONOCLONAL-ANTIBODY; IFN-GAMMA; TH2 CELLS; LEUKEMIA; DEPLETION; IL-2; ALLOENGRAFTMENT AB In a fully MHC plus multiple minor antigen-mismatched murine bone marrow transplantation (EMT) model, we have demonstrated that a short course of high dose IL-2, begun on the day of BMT, protects against graft-versus-host disease (GVHD), This inhibitory effect is directed against donor CD4+ cells, To determine whether the mechanism of IL-S-induced GVHD protection involves clonal deletion or anergy of host-reactive donor T helper cells (Th) we performed limiting dilution analyses to measure the frequency of activated Th that reacted to donor, host, and third-party antigens in GVHD control and IL-2-protected mice, Marked and specific expansion of host-reactive Th was observed to a similar extent in GVHD control and IL-2-protected mice by day 5 after BMT, and the number of these cells in the spleen increased by several. orders of magnitude between days 3 and 5 after BMT, which suggests that recirculation from other tissues occurred in this period, A high proportion (approximately 80%) of donor T cells expressed CD25 in both GVHD control and IL-2-protected mice on day 4 after BMT, which suggests a high level of bystander T cell activation. Since marked quantitative differences in the GVH response were not observed between GVHD control and IL-2-protected mice, we assessed both groups for qualitative differences in the Th response, Spleen cells isolated in the first 8 days after BMT were cultured with host-type, donor-type, or third-party stimulators or without stimulators, and cytokines were measured in supernatants harvested at 24 hr. GVHD was associated with marked increases in supernatant IFN-gamma levels from day 3 to day 6 after BMT, and with increases in IL-2 levels compared with naive A/J controls or syngeneic BMT controls stimulated with host antigens, Production of these cytokines was specifically induced by host-type antigens, Supernatants from spleens of IL-a-treated mice showed delayed kinetics of IFN-gamma production, and tended to contain higher levels of IL-4 in response to host antigen compared with GVHD controls on days 2 and 4 after BMT, Both IL-4 and IFN-gamma were produced almost exclusively by CD4+ cells in spleens of GVHD control and IL-2-protected mice on day 4, However, no consistent difference was observed between the groups in supernatant IL-2 or IL-10 levels, ruling out a simple Th1 to Th2 switch, Neutralizing antibody to IL-4 did not inhibit the protective effect of IL-2 against GVHD, and previous studies have indicated that changes in IFN-gamma kinetics do not explain IL-2-induced GVHD protection. Thus, in vivo high dose exogenous IL-2 treatment does not inhibit the marked Th expansion and T cell activation that occurs in the first week of GVHD, but significantly perturbs the pattern of GVHD-associated CD4 cytokine production. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. FU PHS HHS [55290, 31158] NR 45 TC 23 Z9 25 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD SEP 15 PY 1995 VL 60 IS 5 BP 481 EP 490 DI 10.1097/00007890-199509000-00014 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA RV752 UT WOS:A1995RV75200014 PM 7676498 ER PT J AU SUN, XJ WANG, LM ZHANG, YT YENUSH, L MYERS, MG GLASHEEN, E LANE, WS PIERCE, JH WHITE, MF AF SUN, XJ WANG, LM ZHANG, YT YENUSH, L MYERS, MG GLASHEEN, E LANE, WS PIERCE, JH WHITE, MF TI ROLE OF IRS-2 IN INSULIN AND CYTOKINE SIGNALING SO NATURE LA English DT Article ID HEMATOPOIETIC-CELLS; RECEPTOR; PROTEIN; PHOSPHORYLATION; TRANSMISSION; SEQUENCE AB THE protein IRS-1 acts as an interface between signalling proteins with Src-homology-2 domains (SH2 proteins) and the receptors for insulin, IGF-1, growth hormone, several interleukins (IL-4, IL-9, IL-13) and other cytokines(1-7). It regulates gene expression acid stimulates mitogenesis, and appears to mediate insulin/IGF-1-stimulated glucose transport(8). Thus, survival of the IRS-1(-/-) mouse with only mild resistance to insulin was surprising(9,10). This dilemma is provisionally resolved with our discovery of a second IRS-signalling protein, We purified and cloned a likely candidate called 4PS from myeloid progenitor cells and, because of its resemblance to IRS-1, we designate it IRS-2. Alignment of the sequences of IRS-2 acid IRS-1 revealed a highly conserved amino terminus containing a pleckstrin-homology domain and a phosphotyrosine-binding domain, and a poorly conserved carboxy terminus containing several tyrosine phosphorylation motifs. IRS-2 is expressed in many cells, including tissues from IRS-1(-/-) mice(11), and may be essential for signalling by several receptor systems. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. NIH,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,HARVARD MICROCHEM FACIL,CAMBRIDGE,MA 02138. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 NR 36 TC 700 Z9 711 U1 2 U2 19 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 14 PY 1995 VL 377 IS 6545 BP 173 EP 177 DI 10.1038/377173a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU754 UT WOS:A1995RU75400055 PM 7675087 ER PT J AU HYMAN, SE DELBANCO, TL AF HYMAN, SE DELBANCO, TL TI A MAN WITH ALCOHOLISM AND HIV-INFECTION SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Discussion ID DOPAMINE-D2 RECEPTOR GENE; ASSOCIATION; ETHANOL; NEURONS; ADDICTION; ABUSE; RAT C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NIDA NIH HHS [DA07134, DA00257] NR 34 TC 8 Z9 8 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 13 PY 1995 VL 274 IS 10 BP 837 EP 843 DI 10.1001/jama.274.10.837 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RU324 UT WOS:A1995RU32400033 PM 7650809 ER PT J AU INHORN, RC CARLESSO, N DURSTIN, M FRANK, DA GRIFFIN, JD AF INHORN, RC CARLESSO, N DURSTIN, M FRANK, DA GRIFFIN, JD TI IDENTIFICATION OF A VIABILITY DOMAIN IN THE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR BETA-CHAIN INVOLVING TYROSINE-750 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL-TRANSDUCTION; GM-CSF; PROTEIN; INTERLEUKIN-3; CELLS; SRC; PHOSPHORYLATION; PHOSPHATASE; SUBUNIT; SHC AB The granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor (GMR) is a heterodimeric receptor expressed by myeloid lineage cells, In this study we have investigated domains of the GMR beta-chain (GMR beta) involved in maintaining cellular viability, Using a series of nested GMR beta deletion mutants, we demonstrate that there are at least two domains of GMR beta that contribute to viability signals, Deletion of amino acid residues 626-763 causes a viability defect that can be rescued with fetal calf serum (FCS), Deletion of residues 518-626, in contrast, causes a further decrement in viability that can be only partially compensated by the addition of FCS, GMR beta truncated proximal to amino acid 517 will not support long-term growth under any conditions, Site directed mutagenesis of tyrosine-750 (Y750), which is contained within the distal viability domain, to phenylalanine eliminates all demonstrable tyrosine phosphorylation of GMR beta, Cell lines transfected with mutant GMR beta (Y750 --> F) have a viability disadvantage when compared to cell lines containing wild-type GMR that is partially rescued by the addition of FCS. We studied signal transduction in mutant cell lines in an effort to identify pathways that might participate in the viability signal. Although tyrosine phosphorylation of JAK2, SHPTP2, and Vav is intact in Y750 --> F mutant cell lines, She tyrosine phosphorylation is reduced, This suggests a potential role for Y750 and potentially She in a GM-CSF-induced signaling pathway that helps maintain cellular viability. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DEPT NEUROL,DIV NEUROSCI,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA 34185, CA 36167] NR 25 TC 50 Z9 51 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8665 EP 8669 DI 10.1073/pnas.92.19.8665 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900027 PM 7567993 ER PT J AU SHIVDASANI, RA ORKIN, SH AF SHIVDASANI, RA ORKIN, SH TI ERYTHROPOIESIS AND GLOBIN GENE-EXPRESSION IN MICE LACKING THE TRANSCRIPTION FACTOR NF-E2 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LOCUS CONTROL REGION; GLOBIN ENHANCER; HYPOCHROMIC ANEMIA; GENE TARGETING ID PORPHOBILINOGEN DEAMINASE GENE; DOMINANT CONTROL REGION; LEUCINE ZIPPER PROTEIN; LOCUS-CONTROL REGION; ERYTHROID-CELLS; BINDING; SITES; FERROCHELATASE; ORGANIZATION; EXTRACTION AB Previous studies in transgenic mice and cultured cells have indicated that the major enhancer function for erythroid cell expression of the globin genes is provided by the heterodimeric basic-leucine zipper transcription factor NF-E2. Globin gene expression within cultured mouse erythroleukemia cells is highly dependent on NF-E2. To examine the requirement for this Factor in vivo, we used homologous recombination in embryonic stem cells to generate mice lacking the hematopoietic-specific subunit, p45 NF-E2. The most dramatic aspect of the homozygous mutant mice was an absence of circulating platelets, which led to the death of most animals due to hemorrhage. In contrast, the effect of loss of NF-E2 on the erythroid lineage was surprisingly mild. Although neonates exhibited severe anemia and dysmorphic red-cell changes, probably compounded by concomitant bleeding, surviving adults exhibited only mild changes consistent with a small decrease in the hemoglobin content per cell, p45 NF-E2-null mice responded to anemia with compensatory reticulocytosis and splenomegaly. Globin chain synthesis was balanced, and switching from fetal to adult globins progressed normally, Although these findings are consistent with the substitution of NF-E2 function in vivo by one or more compensating proteins, gel shift assays using nuclear extracts from p45 NF-E2-null mice failed to reveal novel complexes formed on an NF-E2 binding site, Thus, regulation of globin gene transcription through NF-E2 binding sites in vivo is more complex than has been previously appreciated, C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. RP SHIVDASANI, RA (reprint author), DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. NR 35 TC 157 Z9 160 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8690 EP 8694 DI 10.1073/pnas.92.19.8690 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900032 PM 7567998 ER PT J AU REPPERT, SM GODSON, C MAHLE, CD WEAVER, DR SLAUGENHAUPT, SA GUSELLA, JF AF REPPERT, SM GODSON, C MAHLE, CD WEAVER, DR SLAUGENHAUPT, SA GUSELLA, JF TI MOLECULAR CHARACTERIZATION OF A 2ND MELATONIN RECEPTOR EXPRESSED IN HUMAN RETINA AND BRAIN - THE MEL(1B) MELATONIN RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BINDING-SITES; SYSTEMS; CLONING; LIGAND; CLOCK; GENES; MAP AB A G protein-coupled receptor for the pineal hormone melatonin was recently cloned from mammals and designated the Mel(1a) melatonin receptor. We now report the cloning of a second G protein-coupled melatonin receptor from humans and designate it the Mel(1b) melatonin receptor. The Mel(1b) receptor cDNA encodes a protein of 362 amino acids that is 60% identical at the amino acid level to the human Mel(1a) receptor. Transient expression of the Mel(1b) receptor in COS-1 cells results in high-affinity 2-[I-125]iodomelatonin binding (K-d = 160 +/- 30 pM) In addition, the rank order of inhibition of specific 2-[125I]iodomelatonin binding by eight ligands is similar to that exhibited by the Mel(1a) melatonin receptor. Functional studies of NIH 3T3 cells stably expressing the Mel(1b) melatonin receptor indicate that it is coupled to inhibition of adenylyl cyclase. Comparative reverse transcription PCR shows that the Mel(1b) melatonin receptor is expressed in retina and, to a lesser extent, brain, PCR analysis of human-rodent somatic cell hybrids maps the Mel(1b) receptor gene (MTNR1B) to human chromosome 11q21-22. The Mel(1b) melatonin receptor may mediate the reported actions of melatonin in retina and participate in some of the neurobiological effects of melatonin in mammals. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,CNS NEUROPHARMACOL,WALLINGFORD,CT 06492. RP REPPERT, SM (reprint author), MASSACHUSETTS GEN HOSP,DEV CHRONOBIOL LAB,JACKSON 1226,BOSTON,MA 02114, USA. FU NHGRI NIH HHS [F32-HG00073, HG00169]; NIDDK NIH HHS [DK42125] NR 28 TC 643 Z9 668 U1 2 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8734 EP 8738 DI 10.1073/pnas.92.19.8734 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900041 PM 7568007 ER PT J AU MURAGAKI, Y TIMMONS, S GRIFFITH, CM OH, SP FADEL, B QUERTERMOUS, T OLSEN, BR AF MURAGAKI, Y TIMMONS, S GRIFFITH, CM OH, SP FADEL, B QUERTERMOUS, T OLSEN, BR TI MOUSE COL18A1 IS EXPRESSED IN A TISSUE-SPECIFIC MANNER AS 3 ALTERNATIVE VARIANTS AND IS LOCALIZED IN BASEMENT-MEMBRANE ZONES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POLARITY GENE; COLLAGEN; DOMAIN AB We have isolated overlapping cDNAs encoding the N-terminal non-triple-helical region of mouse alpha 1(XVIII) collagen and shown that three different variants of alpha 1(XVIII) collagen exist. Each of the three variants shows characteristic tissue-specific expression, patterns. Immunohistochemical studies show positive staining for alpha 1(XVIII) collagen along the basement membrane zones of vessels in the intestinal villi, the choroid plexus, skin, liver, and kidney. Thus, we conclude that alpha 1(XVIII) collagen may interact (directly or indirectly) with components in basement membrane zones or on the basal surface of endothelial/epithelial cells. C1 VANDERBILT UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37232. UNIV OTTAWA,OTTAWA GEN HOSP,INST EYE,OTTAWA,ON K1H 8L6,CANADA. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02115. RP MURAGAKI, Y (reprint author), HARVARD UNIV,SCH MED,DEPT CELL BIOL,25 SHATTUCK ST,BOSTON,MA 02115, USA. FU NEI NIH HHS [EY07334]; NHLBI NIH HHS [HL33014] NR 24 TC 152 Z9 156 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8763 EP 8767 DI 10.1073/pnas.92.19.8763 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900047 PM 7568013 ER PT J AU HUTCHCROFT, JE FRANKLIN, DP TSAI, B HARRISONFINDIK, D VARTICOVSKI, L BIERER, BE AF HUTCHCROFT, JE FRANKLIN, DP TSAI, B HARRISONFINDIK, D VARTICOVSKI, L BIERER, BE TI PHORBOL ESTER TREATMENT INHIBITS PHOSPHATIDYLINOSITOL 3-KINASE ACTIVATION BY, AND ASSOCIATION WITH, CD28, A T-LYMPHOCYTE SURFACE-RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID KINASE AB CD28 is a costimulatory receptor found on the surface of most T lymphocytes. Engagement of CD28 induces interleukin 2 (IL-2) production and cell proliferation when combined with an additional signal such as treatment with phorbol ester, an activator of protein kinase C, Recent studies have established that after CD28 ligation, the cytoplasmic domain of CD28 can bind to the 85-kDa subunit of phosphatidylinositol 3-kinase (PI3 kinase), There is a concomitant increase in PI3 lipid kinase activity that may be important in CD28 signaling, Despite the requirement of phorbol 12-myristate 13-acetate (PMA) for effector function, we have found, however, that treatment of Jurkat T cells with the phorbol ester PMA dramatically inhibits (i) the association of PI3 kinase with CD28, (ii) the ability of p85 PI3 kinase to be immunoprecipitated by anti-phosphotyrosine antibodies, and (iii) the induction of PI3 kinase activity after stimulation of the cells with the anti-CD28 monoclonal antibody 9.3, These changes occur within minutes of PMA treatment and are persistent, In addition, we have found that wortmannin, a potent inhibitor of PI3 kinase, does not interfere with the induction of IL-2 after stimulation of Jurkat T cells with anti-CD28 monoclonal antibody and PMA, We conclude that PI3 kinase activity may not be required for CD28-dependent IL-2 production from Jurkat T cells in the presence of PMA. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. ST ELIZABETHS HOSP BOSTON,DEPT BIOMED RES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU PHS HHS [T2A107386A] NR 18 TC 34 Z9 34 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8808 EP 8812 DI 10.1073/pnas.92.19.8808 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900056 PM 7568022 ER PT J AU RAAB, M CAI, YC BUNNELL, SC HEYECK, SD BERG, LJ RUDD, CE AF RAAB, M CAI, YC BUNNELL, SC HEYECK, SD BERG, LJ RUDD, CE TI P56(LCK) AND P59(FYN) REGULATE CD28 BINDING TO PHOSPHATIDYLINOSITOL 3-KINASE, GROWTH-FACTOR RECEPTOR-BOUND PROTEIN GRB-2, AND T-CELL-SPECIFIC PROTEIN-TYROSINE KINASE-ITK - IMPLICATIONS FOR T-CELL COSTIMULATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SON OF SEVENLESS; T-CELL ANERGY ID LYMPHOCYTES-T; ACTIVATION; CTLA-4; ANTIGEN; INTERLEUKIN-2; MOLECULES; COMPLEX; LIGAND; SIGNAL; GENE AB T-cell activation requires cooperative signals generated by the T-cell antigen receptor zeta-chain complex (TCR zeta-CD3) and the costimulatory antigen CD28, CD28 interacts with three intracellular proteins-phosphatidylinositol 3-kinase (PI 3-kinase), T cell-specific protein-tyrosine kinase ITK (formerly TSK or EMT), and the complex between growth factor receptor-bound protein 2 and son of sevenless guanine nucleotide exchange protein (GRB-2-SOS), PI 3-kinase End GRB-2 bind to the CD28 phosphotyrosine-based Tyr-Met-Asn-Met motif by means of intrinsic Src-homology 2 (SH2) domains, The requirement for tyrosine phosphorylation of the Tyr-Met-Asn-Met motif for SH2 domain binding implicates an intervening protein-tyrosine kinase in the recruitment of PI 3-kinase and GRB-2 by CD28, Candidate kinases include p56(Lck), p59(Fyn), zeta-chain-associated 70-kDa protein (ZAP-70), and ITK, In this study, we demonstrate in coexpression studies that p56(Lck) and p59(Fyn) phosphorylate CD28 primarily at Tyr-191 of the Tyr-Met-Asn-Met motif, inducing a 3- to 8-fold increase in p85 (subunit of PI 3-kinase) and GRB-2 SH2 binding to CD28, Phosphatase digestion of CD28 eliminated binding, In contrast to Src kinases, ZAP-70 and ITK failed to induce these events, Further, ITK binding to CD28 was dependent on the presence of p56(Lck) and is thus likely to act downstream of p56(Lck)/p59(Fyn) in a signaling Cascade, p56(Lck) is therefore likely to be a central switch in T-cell activation, with the dual function of regulating CD28-mediated costimulation as well as TCR-CD3-CD4 signaling. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,DEPT MOLEC & CELLULAR BIOL,CAMBRIDGE,MA 02128. FU NCI NIH HHS [CA51887] NR 53 TC 144 Z9 146 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8891 EP 8895 DI 10.1073/pnas.92.19.8891 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900073 PM 7568038 ER PT J AU ROTHENBERG, ME LUSTER, AD LEDER, P AF ROTHENBERG, ME LUSTER, AD LEDER, P TI MURINE EOTAXIN - AN EOSINOPHIL CHEMOATTRACTANT INDUCIBLE IN ENDOTHELIAL-CELLS AND IN INTERLEUKIN 4-INDUCED TUMOR SUPPRESSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ALIGNMENT; INVITRO; GROWTH; MICE AB Guinea pig eotaxin is a recently described member of the Cys-Cys family of chemokines and is involved in a guinea pig model of asthma. To determine whether eotaxin is a distinctive member of this family and to understand its physiologic role, we have cloned the mouse eotaxin gene and determined its structure and aspects of its biologic function. The sequence relationship between the mouse and guinea pig genes indicates that eotaxin is indeed a distinct member of the chemokine family, Moreover, murine eotaxin maps to a region of mouse chromosome 11 that encodes other Cys-Cys chemokines. In addition, recombinant murine eotaxin protein has direct chemoattractant properties for eosinophils. The eotaxin gene is widely (but not ubiquitously) expressed in normal mice and is strongly induced in cultured endothelial cells in response to interferon gamma. Eotaxin is also induced locally in response to the transplantation of interleukin 4-secreting tumor cells, indicating that it likely contributes to the eosinophil recruitment and antitumor effect of interleukin 4. Such responses suggest that eotaxin may be involved in multiple inflammatory states. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,DEPT MED,INFECT DIS UNIT,BOSTON,MA 02129. RP ROTHENBERG, ME (reprint author), HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT GENET,200 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK43351] NR 29 TC 292 Z9 295 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 1995 VL 92 IS 19 BP 8960 EP 8964 DI 10.1073/pnas.92.19.8960 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RU759 UT WOS:A1995RU75900087 PM 7568052 ER PT J AU BARSKY, AJ CLEARY, PD COEYTAUX, RR RUSKIN, JN AF BARSKY, AJ CLEARY, PD COEYTAUX, RR RUSKIN, JN TI THE CLINICAL COURSE OF PALPITATIONS IN MEDICAL OUTPATIENTS SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; NO CORONARY-DISEASE; CHEST PAIN; FOLLOW-UP; SOMATOSENSORY AMPLIFICATION; FUNCTIONAL STATUS; MENTAL-HEALTH; PRIMARY CARE; HYPOCHONDRIASIS; SYMPTOMS AB Objective: The aim of this study was to describe the longitudinal course of patients who were referred for ambulatory electrocardiographic monitoring because of palpitations. Methods: A prospective, follow-up examination was conducted of patients who had been studied 6 months previously when referred for monitoring. The inception cohort consisted of 145 consecutive patients with palpitations and 70 asymptomatic, nonpatient volunteers. At follow-up, the patients completed the same research battery as at inception, consisting of structured interviews and self-report questionnaires. These assessed cardiac symptoms, medical care use, role impairment, somatization, hypochondriacal fears and beliefs, and psychiatric disorder. Results: At 6 months' follow-up, 130 patients with palpitations (89.7% of the original cohort) and 69 nonpatients (98.6%) were reinterviewed. Eighty-four percent of the patients had recurrent palpitations during the 6-month follow-up period. At follow-up, patients with palpitations scored significantly higher than the comparison group on measures of cardiac symptoms and role impairment, and had made more physician visits in the preceding 6 months. They had a higher prevalence of panic disorder and more psychopathologic symptoms, somatized more, and were more hypochondriacal. Psychiatric symptoms and the tendency to amplify bodily sensation, measured at inception, were significant but modest predictors of subsequent palpitations. There was considerable confusion and misunderstanding among patients as to the findings of their ambulatory electrocardiogram and the presence or absence of panic disorder. Conclusions: Patients with palpitations remain symptomatic and functionally impaired and have increased rates of physician visits in the 6 months following Holter monitoring. They also continue to have elevated rates of panic disorder and to evidence some confusion about the cause of their symptoms. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. RP BARSKY, AJ (reprint author), BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL43216] NR 40 TC 39 Z9 40 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern Med. PD SEP 11 PY 1995 VL 155 IS 16 BP 1782 EP 1788 DI 10.1001/archinte.155.16.1782 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA RT780 UT WOS:A1995RT78000010 PM 7654112 ER PT J AU YOSHIMOTO, Y LIN, Q COLLIER, TJ FRIM, DM BREAKEFIELD, XO BOHN, MC AF YOSHIMOTO, Y LIN, Q COLLIER, TJ FRIM, DM BREAKEFIELD, XO BOHN, MC TI ASTROCYTES RETROVIRALLY TRANSDUCED WITH BDNF ELICIT BEHAVIORAL IMPROVEMENT IN A RAT MODEL OF PARKINSONS-DISEASE SO BRAIN RESEARCH LA English DT Article DE RETROVIRUS; GENE TRANSFER; NEURAL TRANSPLANTATION; RAT; TYROSINE HYDROXYLASE; 6-HYDROXYDOPAMINE; EX VIVO GENE THERAPY ID FIBROBLAST GROWTH-FACTOR; MESENCEPHALIC DOPAMINERGIC-NEURONS; EMBRYONAL CARCINOMA-CELLS; NEUROTROPHIC FACTOR; SUBSTANTIA-NIGRA; ROTATIONAL BEHAVIOR; EXCITOTOXIC LESIONS; MESSENGER-RNAS; FACTOR-I; CULTURE AB Neurotrophic factors that improve the survival of specific neuronal types during development and after exposure to various neuronal insults hold potential for treatment of neurodegenerative diseases. In particular, brain-derived neurotrophic factor (BDNF) has been shown to exert trophic and protective effects on dopaminergic neurons, the cell type known to degenerate in Parkinson's disease. To determine whether increased levels of biologically produced BDNF affect the function or regeneration of damaged dopaminergic neurons, the effects of grafting astrocytes transduced with the human BDNF gene into the striatum of the partially lesioned hemiparkinsonian rat were examined. Replication deficient retroviruses carrying either human prepro-BDNF or human alkaline phosphatase (AP) cDNA were used to transduce primary type 1 astrocytes purified from neonatal rat cortex. In vitro, BDNF mRNA was expressed by BDNF transduced astrocytes (BDNF astrocytes), but not control Af transduced astrocytes (AP astrocytes), as determined by reverse transcription polymerase chain reaction (RT-PCR). The modified astrocytes were injected into the right striatum 15 days after partial lesioning of the right substantia nigra with 6-hydroxydopamine. Transplantation of BDNF astrocytes, but not AP astrocytes, significantly attenuated amphetamine-induced rotation by 45% 32 days after grafting. Apomorphine-induced rotation increased over time in both groups, but was not significantly different in the BDNF-treated group. The modified BDNF astrocytes survived well with non-invasive growth in the brain for up to 42 days. Although BDNF mRNA positive cells were not detected within the graft site using in situ hybridization, alkaline phosphatase immunoreactive (IR) cells were present in control graft sites suggesting that the retroviral construct continued to be expressed at 42 days. Analysis of the density of tyrosine hydroxylase (TH)-IR seers showed no effect of BDNF on TH-IR fiber density in the striatum on the lesioned side. These findings suggest that ex vivo gene therapy with BDNF ameliorates parkinsonian symptoms through a mechanism(s) other than one involving an effect of BDNF on regeneration or sprouting from dopaminergic neurons. C1 UNIV ROCHESTER,MED CTR,SCH MED & DENT,DEPT ANAT & NEUROBIOL,ROCHESTER,NY 14642. UNIV HARTFORD,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA. NR 72 TC 112 Z9 116 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 11 PY 1995 VL 691 IS 1-2 BP 25 EP 36 DI 10.1016/0006-8993(95)00596-I PG 12 WC Neurosciences SC Neurosciences & Neurology GA RV411 UT WOS:A1995RV41100004 PM 8590062 ER PT J AU HUGDAHL, K BERARDI, A THOMPSON, WL KOSSLYN, SM MACY, R BAKER, DP ALPERT, NM LEDOUX, JE AF HUGDAHL, K BERARDI, A THOMPSON, WL KOSSLYN, SM MACY, R BAKER, DP ALPERT, NM LEDOUX, JE TI BRAIN MECHANISMS IN HUMAN CLASSICAL-CONDITIONING - A PET BLOOD-FLOW STUDY SO NEUROREPORT LA English DT Article DE BLOOD FLOW; PET; CLASSICAL CONDITIONING AB FIVE healthy male subjects participated in a classical conditioning experiment, and positron emission tomography (PET) was used to compare regional cerebral blood flow before and after conditioning. The subjects participated in three different experimental phases. In the first (habituation) phase they listened to 24 repetitions of a tone with random intervals. In the second (acquisition) phase, the tone was paired with a brief shock to the wrist. In the third (extinction) phase, the tone was presented alone again. (15)OPET scans were taken during the habituation and extinction phases. Because the habituation and extinction phases were similar, any difference in blood flow to the tones presented during extinction probably reflected conditioning that occurred during the acquisition phase. Statistical parametric mapping (SPM) analysis of the PET data showed significantly increased activation in the right hemisphere in the orbito-frontal cortex, dorsolateral prefrontal cortex, inferior and superior frontal corticies, and inferior and middle temporal corticies. The only activated areas in the left hemisphere were area 19 and the superior frontal cortex. The results are interpreted as evidence for the involvement of cortical areas in human classical conditioning. C1 HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NYU,CTR NEURAL SCI,NEW YORK,NY 10003. RP HUGDAHL, K (reprint author), UNIV BERGEN,DEPT BIOL & MED PSYCHOL,ARSTADVEIEN 21,N-5009 BERGEN,NORWAY. NR 24 TC 91 Z9 91 U1 1 U2 9 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 11 PY 1995 VL 6 IS 13 BP 1723 EP 1728 DI 10.1097/00001756-199509000-00005 PG 6 WC Neurosciences SC Neurosciences & Neurology GA RW478 UT WOS:A1995RW47800005 PM 8541468 ER PT J AU DERMODY, TS CHAPPELL, JD HOFLER, JG KRAMP, W TYLER, KL AF DERMODY, TS CHAPPELL, JD HOFLER, JG KRAMP, W TYLER, KL TI ERADICATION OF PERSISTENT REOVIRUS INFECTION FROM A B-CELL HYBRIDOMA SO VIROLOGY LA English DT Note ID VIRUS PERSISTENCE; VIRAL-INFECTION; HEMAGGLUTININ; RECEPTORS; TYPE-3; LYMPHOCYTES; SEQUENCE; MURINE; LEADS; RNA AB The 2G10 B-cell hybridoma was found to be persistently infected with reovirus serotype 3 (RV3). The persistently infected 2G10 culture produced approximately 1 X 10(8) plaque-forming units of virus per milliliter of culture lysate, and a majority of cells in the culture were infected, as determined by infectious center assay and immunocytochemistry. Cure of the persistent infection was achieved by passaging 2G10 cells for 33 days (12 passages) in medium containing polyclonal anti-RV3 antiserum and a monoclonal antibody specific for the RV3 attachment protein. After several passages in antibody-free medium, cured 2G10 cells had (1) nondetectable levels of RV3 in cell-culture lysates, (2) no infectious centers per 3 X 10(8) cells, (3) no immunocytochemically detectable RV3 antigen, and (4) no detectable reovirus-specific RNA by reverse transcription-polymerase chain reaction amplification. Additionally, mice inoculated with cured 2G10 cell lysates did not generate antibodies directed against RV3. These observations demonstrate that persistent reovirus infection of a B-cell hybridoma can be cured by passage in medium containing anti-reovirus antibodies and suggest that the maintenance of this persistent infection is dependent on horizontal cell-to-cell transmission of virus in the culture. (C) 1995 Academic Press, Inc. C1 VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,NASHVILLE,TN 37232. CENTOCOR INC,DEPT IN VITRO RES & DEV,MALVERN,PA 19355. UNIV COLORADO,HLTH SCI CTR,DEPT NEUROL,DENVER,CO 80220. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DENVER,CO 80220. UNIV COLORADO,HLTH SCI CTR,DEPT IMMUNOL MICROBIOL,DENVER,CO 80220. DENVER VET AFFAIRS MED CTR,NEUROL SERV 127,DENVER,CO 80220. RP DERMODY, TS (reprint author), VANDERBILT UNIV,SCH MED,ELIZABETH B LAMB CTR PEDIAT RES,D6227 MCN,NASHVILLE,TN 37232, USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NIAID NIH HHS [AI32539] NR 28 TC 13 Z9 13 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 10 PY 1995 VL 212 IS 1 BP 272 EP 276 DI 10.1006/viro.1995.1483 PG 5 WC Virology SC Virology GA RV178 UT WOS:A1995RV17800037 PM 7676645 ER PT J AU SAEZ, E RUTBERG, SE MUELLER, E OPPENHEIM, H SMOLUK, J YUSPA, SH SPIEGELMAN, BM AF SAEZ, E RUTBERG, SE MUELLER, E OPPENHEIM, H SMOLUK, J YUSPA, SH SPIEGELMAN, BM TI C-FOS IS REQUIRED FOR MALIGNANT PROGRESSION OF SKIN TUMORS SO CELL LA English DT Article ID MOUSE SKIN; TRANSGENIC MICE; GENE-EXPRESSION; CELL CARCINOMAS; PHORBOL ESTERS; RETINOIC ACID; NULL MUTATION; BENIGN-TUMORS; HUMAN-BREAST; JUN AB The proto-oncogene c-fos is a major nuclear target for signal transduction pathways involved in the regulation of cell growth, differentiation, and transformation. Using the multistep skin carcinogenesis model, we have directly tested the ability of c-fos-deficient mice to develop cancer. Upon treatment with a tumor promoter, c-fos knockout mice carrying a v-H-ras transgene were able to develop benign tumors with similar kinetics and relative incidence as wild-type animals. However, c-fos-deficient papillomas quickly became very dry and hyperkeratinized, taking on an elongated, horny appearance. While wild-type papillomas eventually progressed into malignant tumors, c-fos-deficient tumors failed to undergo malignant conversion. Experiments in which v-H-ras-expressing keratinocytes were grafted onto nude mice suggest that c-fos-deficient cells have an intrinsic defect that hinders tumorigenesis. These results demonstrate that a member of the AP-1 family of transcription factors is required for the development of a malignant tumor. C1 HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP SAEZ, E (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NICHD NIH HHS [HD27295] NR 60 TC 303 Z9 310 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 8 PY 1995 VL 82 IS 5 BP 721 EP 732 DI 10.1016/0092-8674(95)90469-7 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA RU755 UT WOS:A1995RU75500007 PM 7545543 ER PT J AU ROSENWALD, IB KASPAR, R ROUSSEAU, D GEHRKE, L LEBOULCH, P CHEN, JJ SCHMIDT, EV SONENBERG, N LONDON, IM AF ROSENWALD, IB KASPAR, R ROUSSEAU, D GEHRKE, L LEBOULCH, P CHEN, JJ SCHMIDT, EV SONENBERG, N LONDON, IM TI EUKARYOTIC TRANSLATION INITIATION-FACTOR 4E REGULATES EXPRESSION OF CYCLIN D1 AT TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL LEVELS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-SYNTHESIS INITIATION; RNA 5' CAP; MESSENGER-RNA; CELL-CYCLE; GENE-EXPRESSION; MALIGNANT TRANSFORMATION; RODENT FIBROBLASTS; LYMPHOCYTES-T; GROWTH; PHOSPHORYLATION AB Regulation of the cell cycle is orchestrated by cyclins and cyclin-dependent kinases. We have demonstrated previously that overexpression of eukaryotic translation initiation factor 4E (eIF-4E) in NIH 3T3 cells growing in 10% fetal calf serum leads to highly elevated levels of cyclin D1 protein without significant increase in cyclin D1 mRNA levels, suggesting that a post-transcriptional mechanism is involved. (Rosenwald, I. B., Lazaris-Karatzas, A., Sonenberg, N., and Schmidt, E. V. (1993) Mol. Cell. Biol. 13, 7358-7363). In the present reseach, we did not find any significant effect of eIF-4E on polysomal distribution of cyclin D1 mRNA. However, the total amount of cyclin D1 mRNA associated with polysomes was significantly increased by eIF-4E overexpression. Further, we determined that the levels of both cyclin D1 protein and mRNA are increased in serum-deprived cells overexpressing eIF-4E. Nuclear run-on experiments demonstrated that the rate of the cyclin D1 transcription is not down-regulated in serum-deprived cells overexpressing eIF-4E. Thus, elevated levels of eIF-4E may lead to increased transcription of the cyclin D1 gene, and this effect becomes visible when serum deprivation down-regulates the rate of cyclin D1 mRNA synthesis in control cells. However, artificial overexpression of cyclin D1 mRNA in serum-deprived cells in the absence of eIF-4E overexpression did not cause the elevation of cyclin D1 protein, and this overexpressed cyclin D1 mRNA accumulated in the nucleus, suggesting that one post-transcriptional role of eIF-4E is to transport cyclin D1 mRNA from the nucleus to cytoplasmic polysomes. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. MCGILL UNIV,DEPT BIOCHEM,MONTREAL,PQ H3G 1Y6,CANADA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,BOSTON,MA 02129. RP ROSENWALD, IB (reprint author), HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139, USA. FU NCI NIH HHS [R01-CA63117-01]; NIDDK NIH HHS [R01 DK016272, DK-16272]; NIGMS NIH HHS [GM-42504, R01 GM042504] NR 40 TC 201 Z9 203 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 1995 VL 270 IS 36 BP 21176 EP 21180 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU054 UT WOS:A1995RU05400049 PM 7673150 ER PT J AU RUSS, G ESQUIVEL, F YEWDELL, JW CRESSWELL, P SPIES, T BENNICK, JR AF RUSS, G ESQUIVEL, F YEWDELL, JW CRESSWELL, P SPIES, T BENNICK, JR TI ASSEMBLY, INTRACELLULAR-LOCALIZATION, AND NUCLEOTIDE-BINDING PROPERTIES OF THE HUMAN PEPTIDE TRANSPORTERS TAP1 AND TAP2 EXPRESSED BY RECOMBINANT VACCINIA VIRUSES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; ENDOPLASMIC-RETICULUM; ANTIGEN PRESENTATION; MEMBRANE-PROTEINS; ABC TRANSPORTER; LYMPHOCYTES-T; MHC; REGION; TRANSLOCATION AB The transporter associated with antigen processing (TAP) transports short peptides from the cytosol to the endoplasmic reticulum, where peptides assemble with class I molecules of the major histocompatibility complex, TAP is comprised of two subunits, termed TAP1 and TAP2, We produced recombinant vaccinia viruses that direct synthesis of the TAP subunits, either individually or together, Virus-encoded TAP is rapidly and efficiently assembled (t(1/2) of 5 min or less) by cells and does not spontaneously assemble in detergent extracts, By confocal immunofluorescence microscopy, TAP1 when expressed alone or with TAP2 is largely, if not exclusively, localized to the endoplasmic reticulum, Metabolic labeling with [2-H-3]mannose demonstrates that TAP1 (but not TAP2) possesses Asn-Linked oligosaccharides, but the lack of binding of [S-35]methionine-labeled TAP to concanavalin A-agarose suggests that the glycosylated form represents a minor population of TAP1, The two subunits of the assembled complex present in detergent extracts photolabeled equally with 8-azido-[alpha-P-32]ATP. Photolabeling of the two subunits was inhibited in parallel by various di- and trinucleotides, suggesting that their nucleotide binding sites function in a highly similar manner, Incubation of detergent extracts at 37 degrees C results in the rapid loss of TAP1 immunoreactivity, indicating either an unusual sensitivity to proteases or an irreversible conformation alteration. C1 YALE UNIV,HOWARD HUGHES MED INST,NEW HAVEN,CT 06510. DANA FARBER CANC INST,BOSTON,MA 02115. RP RUSS, G (reprint author), NIAID,VIRAL DIS LAB,BLDG 4,ROOM 205,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 56 TC 69 Z9 69 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 1995 VL 270 IS 36 BP 21312 EP 21318 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RU054 UT WOS:A1995RU05400068 PM 7673167 ER PT J AU KIBEL, A ILIOPOULOS, O DECAPRIO, JA KAELIN, WG AF KIBEL, A ILIOPOULOS, O DECAPRIO, JA KAELIN, WG TI BINDING OF THE VONHIPPEL-LINDAU TUMOR-SUPPRESSOR PROTEIN TO ELONGIN-B AND ELONGIN-C SO SCIENCE LA English DT Article ID GENE; IDENTIFICATION; SEQUENCE; PRODUCT AB Germ-line mutations of the von Hippel-Lindau tumor suppressor gene (VHL) predispose individuals to a variety of human tumors, and somatic mutations of this gene have been identified in sporadic renal cell carcinomas and cerebellar hemangioblastomas. Two transcriptional elongation factors, Elongin B and C, were shown to bind in vitro and in vivo to a short, colinear region of the VHL protein (pVHL) that is frequently mutated in human tumors. A peptide replica of this region inhibited binding of pVHL to Elongin B and C, whereas a point-mutant derivative, corresponding to a naturally occurring VHL missense mutation, had no effect. These results suggest that the tumor suppression function of pVHL may be linked to its ability to bind to Elongin B and C. C1 CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. NR 25 TC 483 Z9 494 U1 0 U2 9 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 8 PY 1995 VL 269 IS 5229 BP 1444 EP 1446 DI 10.1126/science.7660130 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA RT806 UT WOS:A1995RT80600051 PM 7660130 ER PT J AU RAHMAN, MU HUDSON, AP AF RAHMAN, MU HUDSON, AP TI SUBSTRATES FOR YEAST MITOCHONDRIAL CAMP-DEPENDENT PROTEIN-KINASE ACTIVITY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CYCLIC-AMP; RNA-POLYMERASE; TRANSCRIPTION FACTOR; STRINGENT RESPONSE; BINDING; PHOSPHORYLATION; GENES; ELEMENT; DNA AB We showed that transcription of mitochondrial (mt) genes in Saccharomyces cerevisiae is governed in part by cellular cAMP levels, and that such transcriptional control is mediated via cAMP-dependent protein kinase (cAPK) activity. Here we use in vitro protein kinase assays with intact mitochondria from respiring cells to define protein substrates for mt cAPK. Our data show that there are at least eight mt proteins phosphorylated in a cAMP-dependent manner, ranging in M(r) from 96000 to 9500. Similar assays with organelles from an mtf1 mutant and its wild-type parent strain show no loss of any mt cAPK target proteins, suggesting that Mtf1p (M(r)=40000), the mt RNA polymerase specificity factor, does not require phosphorylation for activity. We further show, using double mutants for TPK1, TPK2, and TPK3, which encode catalytic subunits of the mt cAPY that each of the eight mt substrate proteins is not phosphorylated equivalently by the individual catalytic subunits. (C) 1995 Academic Press, Inc. C1 DEPT VET AFFAIRS MED CTR,MED RES SERV,PHILADELPHIA,PA 19104. HAHNEMANN UNIV,MED COLL PENN,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19104. NR 25 TC 14 Z9 14 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 5 PY 1995 VL 214 IS 1 BP 188 EP 194 DI 10.1006/bbrc.1995.2273 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA RT426 UT WOS:A1995RT42600026 PM 7669038 ER PT J AU WAEBER, C MOSKOWITZ, MA AF WAEBER, C MOSKOWITZ, MA TI AUTORADIOGRAPHIC VISUALIZATION OF [H-3] 5-CARBOXAMIDOTRYPTAMINE BINDING-SITES IN THE GUINEA-PIG AND RAT-BRAIN SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE 5-HT1D, RECEPTOR; 5-HT1A, RECEPTOR; 5-HT7 RECEPTOR ID SEROTONIN RECEPTORS; HIGH-AFFINITY; DURA-MATER; CLONING; EXPRESSION; LOCALIZATION; CYCLASE; ANALOGS AB We have investigated the distribution of [H-3]5-carboxamidotryptamine ([H-3]5-CT) binding sites by in vitro autoradiography on sections of guinea-pig and rat brain. In saturation studies, the ligand recognised a saturable, homogeneous population of binding sites with an affinity ranging from 0.19-0.45 nM depending on the region. The labelling pattern was heterogeneous, and the displacement pattern with different competing drugs selective for different 5-HT receptor subtypes was complex. [H-3]5-CT appeared to label 5-HT1B/5-HT1D sites in the substantia nigra, globus pallidus and caudate/putamen, as the binding in these regions was displaced by the 5-HT1B/1D receptor selective agents sumatriptan, CP-122,288 and GR-127,935. In the hippocampus and lateral septum, the very dense [H-3]5-CT binding was displaced with high affinity by the 5-HT1A receptor selective agonist 8-hydroxy-dipropylaminotetralin ((+/-)-8-OH-DPAT), dihydroergotamine and 5-HT. In contrast the affinity of the 5-HT1 receptor antagonists spiperone and methiothepine was much lower than their previously published potency at 5-HT1A receptors. The affinity of agonists, taken together with the fact that the distribution of these [H-3]5-CT sites overlaps that of [H-3]8-OH-DPAT binding sites in serial sections, suggest that these sites correspond to 5-HT1A receptors. Their atypical properties deserve further investigations. While [H-3]5-CT binding at 5-HT1B/1D sites and these atypical 5-HT1A sites was inhibited by the GTP analogue 5'-beta,gamma-imidotriphosphate, [H-3]5-CT binding in the superficial cortical layers and in midline thalamic nuclei was insensitive to this agent. It was however displaced by low concentrations of spiperone, clozapine and methiothepine, but not by sumatriptan, CP-122,288, GR-127,935 or dihydroergotamine. This binding profile is similar to that of 5-HT7 receptors, while the spatial distribution of these sites matches the known distribution of 5-HT7 messenger RNA. We did not find evidence of [H-3]5-CT labelling to 5-HT5 receptors, in spite of their reported high affinity for this ligand. It is concluded that [H-3]5-CT, in the presence of selective blockers, can be used to investigate the properties of 5-HT1A, 5-HT1B/1D and 5-HT7 receptors in the rodent brain, although further studies are required to explain the atypical features of [H-3]5-CT binding in 5-HT1A receptors containing regions. RP WAEBER, C (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,DEPT SURG,NEUROSURG SERV,CNY149 6403,BOSTON,MA 02129, USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 29 TC 54 Z9 55 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 5 PY 1995 VL 283 IS 1-3 BP 31 EP 46 DI 10.1016/0014-2999(95)00275-P PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RU504 UT WOS:A1995RU50400004 PM 7498319 ER PT J AU DARIUS, S WOLF, G HUANG, PL FISHMAN, MC AF DARIUS, S WOLF, G HUANG, PL FISHMAN, MC TI LOCALIZATION OF NADPH-DIAPHORASE/NITRIC OXIDE SYNTHASE IN THE RAT RETINA - AN ELECTRON-MICROSCOPIC STUDY SO BRAIN RESEARCH LA English DT Note DE NITRIC OXIDE SYNTHASE; NADPH-DIAPHORASE; RETINA; KNOCK-OUT MICE; ELECTRON MICROSCOPY; BSPT-FORMAZAN; MEMBRANE ID NITRIC-OXIDE; RABBIT RETINA; AMACRINE CELLS; BRAIN; GLUTAMATE; LIGHT AB The activity of NADPH-diaphorase (NADPH-d), a marker for nitric oxide synthase (NOS), was examined histochemically in the rat and mice retina. Mice in which the neuronal NOS gene has been disrupted (nNOS(-) mice) were used for specificity controls. Light microscopically a few amacrine cells were heavily stained. Other cells were stained weakly or not at all. Under the electron microscope, formazan precipitates were detectable on membranes of endoplasmic reticulum, nuclear envelope, mitochondria, and, in a few cases, the Golgi complex. Bipolar, horizontal, and Muller cells, were if at all, sparsely labeled with formazan. Labeled mitochondria were observed in rod endings and in inner segments of photoreceptors. Outer segments of photoreceptors and ganglion cells were completely free of reaction product. The NADPH-d reaction in wild-type mice displayed a similar distribution pattern to that in rats. Retinae of nNOS(-) mice showed a complete lack of prominent NADPH-d stained (amacrine) cells. Non or a very few labeled membranes were seen. C1 UNIV MAGDEBURG,INST MED NEUROBIOL,D-39112 MAGDEBURG,GERMANY. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,SCH MED,CARDIOVASC RES CTR,BOSTON,MA 02129. FU NINDS NIH HHS [P01-NS10828, R01-NS3335] NR 30 TC 52 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 4 PY 1995 VL 690 IS 2 BP 231 EP 235 DI 10.1016/0006-8993(95)00559-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA RU452 UT WOS:A1995RU45200011 PM 8535841 ER PT J AU GOLDBERG, SN GAZELLE, GS COMPTON, CC MCLOUD, TC AF GOLDBERG, SN GAZELLE, GS COMPTON, CC MCLOUD, TC TI RADIOFREQUENCY TISSUE ABLATION IN THE RABBIT LUNG - EFFICACY AND COMPLICATIONS SO ACADEMIC RADIOLOGY LA English DT Article DE LUNGS; RADIOFREQUENCY; TISSUE ABLATION; INTERVENTIONAL PROCEDURES ID ELECTRODE AB Rationale and Objectives. We assessed the feasibility and safety of performing percutaneous radiogfrequency ablation of pulmonary tissue in rabbits. Methods. Using an aseptic technique and computed tomography (CT) guidance, insulated 19-gauge aspiration biopsy needles were inserted into the light lower lobe of eight New Zealand White rabbits. Radiofrequency was applied via a coaxial electrode for 6 min at 90 degrees C. Probe-tip temperature, tissue impedance, and wattage were recorded at baseline and at 60-sec intervals throughout the procedure. CT scanning was used to assess tissue destruction and the presence or absence of pneumothorax immediately after the procedure and at 24 hr, 3 days, 10 days, 21 days, and 28 days. Three rabbits were sacrificed immediately, and the remaining rabbits were euthanized at 24 hr and at 3 days, 10 days, and 28 days (two rabbits). Gross and microscopic pathology were obtained and correlated with CT findings. Results. The mean initial tissue impedance was 509 +/- 197 Omega; marked changes in tissue impedance were found during the procedure (240-1380 Omega). Rigid temperature control required continuous manual fine-tuning of generator output. Increased respiratory rate was noted in one rabbit during the first 30 sec of radiofrequency application. Homogeneous, ovoid opacities 8.4 +/- 2.4 mm in diameter and 1.4 +/- 0.1 cm in length were found by CT scanning immediately after the procedure. These opacities showed maximal consolidation at 3 days, corresponding to coagulative necrosis and a peripheral acute inflammatory reaction. At 10 days, peripheral hyperattenuation with central hypoattenuation (early fibrosis surrounding degenerating blood products) was seen. Minimal residual fibrosis, pleural scarring, or both were noted by 28 days, suggesting a rapid, near-total recovery from the procedure. Lesion sizes were within 2 mm of gross pathologic findings. Pneumothoraces were noted in three of the eight rabbits (37.5%). Conclusion. Radiofrequency tissue ablation was safely performed in pulmonary parenchyma via a percutaneous, transthoracic approach using a coaxial needle technique. Tissue response to thermal injury was predictable and easily monitored by CT scanning with excellent radiologic-pathologic correlation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. RP GOLDBERG, SN (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 12 TC 128 Z9 135 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 1995 VL 2 IS 9 BP 776 EP 784 DI 10.1016/S1076-6332(05)80852-9 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RR242 UT WOS:A1995RR24200006 PM 9419639 ER PT J AU WEISSKOFF, R ROSEN, BR AF WEISSKOFF, R ROSEN, BR TI FUNCTIONAL MAGNETIC-RESONANCE-IMAGING SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Conference on Developing a Long-Term Plan for Imaging Research CY NOV 05-08, 1994 CL BETHESDA, MD SP NIH, NCI C1 MASSACHUSETTS GEN HOSP,CTR NUCL MAGNET RESONANCE,BOSTON,MA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI RESTON PA 1891 PRESTON WHITE DR, RESTON, VA 22091 SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 1995 VL 2 SU 2 BP S133 EP S135 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RT158 UT WOS:A1995RT15800022 PM 9419725 ER PT J AU CLEMENT, G DARLOT, C PETROPOULOS, A BERTHOZ, A AF CLEMENT, G DARLOT, C PETROPOULOS, A BERTHOZ, A TI EYE-MOVEMENTS AND MOTION PERCEPTION INDUCED BY OFF-VERTICAL AXIS ROTATION (OVAR) AT SMALL ANGLES OF TILT AFTER SPACEFLIGHT SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE OVAR; OTOLITH; ADAPTATION; MICROGRAVITY ID EUROPEAN VESTIBULAR EXPERIMENTS; SPACELAB-1 MISSION; PROLONGED WEIGHTLESSNESS; FLIGHT AB The nystagmus and motion perception of two astronauts were recorded during Earth-vertical axis rotation and during off-vertical axis rotation (OVAR) before and after 7 days of spaceflight. Postflight, the peak velocity and duration of per- and postrotatory nystagmus during velocity steps about the Earth-vertical axis were the same as preflight values. During OVAR at constant velocity (45/s, tilt angles successively 5, 10, and 15 degrees), the mean horizontal slow-phase eye velocity (bias), produced by the 'velocity storage mechanism' in the vestibular system, and the peak-to-peak amplitude (modulation) in horizontal eye velocity and position, generated from the output of otolith afferents, were also the same before as after flight. There were, however, changes in the vertical eye position and in the perceived body motion during OVAR. The angle of the perceived body path described as a cone was larger in both astronauts postflight. One astronaut experienced either a large cone angle with its axis upright, or a smaller cone angle with its axis tilted backwards, accompanied by an upward vertical eye drift. These results suggest an increase in the sensitivity of the otolithic system after spaceflight and a longer period of readaptation to Earth's gravity for otolith-induced responses than for canal-induced responses. Our data support the hypothesis that just after spaceflight the CNS generally interprets changes in the otolith signals to be due to translation rather than to tilt. C1 ENST,CNRS,TRAITEMENT & COMMUN INFORMAT LAB,PARIS,FRANCE. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,BOSTON,MA 02114. RP CLEMENT, G (reprint author), COLL FRANCE,CNRS,PHYSIOL PERCEPT & ACT LAB,15 RUE ECOLE MED,F-75270 PARIS 06,FRANCE. NR 28 TC 8 Z9 8 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD SEP PY 1995 VL 115 IS 5 BP 603 EP 609 DI 10.3109/00016489509139374 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA RV391 UT WOS:A1995RV39100004 PM 8928630 ER PT J AU ARONEN, HJ GLASS, J PARDO, FS BELLIVEAU, JW GRUBER, ML BUCHBINDER, BR GAZIT, IE LINGGOOD, RM FISCHMAN, AJ ROSEN, BR HOCHBERG, FH AF ARONEN, HJ GLASS, J PARDO, FS BELLIVEAU, JW GRUBER, ML BUCHBINDER, BR GAZIT, IE LINGGOOD, RM FISCHMAN, AJ ROSEN, BR HOCHBERG, FH TI ECHO-PLANAR MR CEREBRAL BLOOD-VOLUME MAPPING OF GLIOMAS - CLINICAL UTILITY SO ACTA RADIOLOGICA LA English DT Article DE GLIOMA; CEREBRAL BLOOD VOLUME; MR IMAGING; ECHO-PLANAR MR ID POSITRON EMISSION TOMOGRAPHY; MALIGNANT GLIOMAS; BRAIN-TUMORS; CONTRAST ENHANCEMENT; RADIATION NECROSIS; ASTROCYTOMAS; DIFFERENTIATION; RADIOTHERAPY; CHEMOTHERAPY; FLOW AB Neovascularization is a common phenomenon in gliomas. MR imaging cerebral blood volume (CBV) mapping utilizes ultrafast echo-planar imaging and simultaneous use of gadolinium-based contrast material. To determine the utility of MR CBV mapping in the clinical evaluation of gliomas, we followed 15 patients with serial studies. This technique provided functional information that was not evident with conventional CT or MR imaging. Low-grade tumors demonstrated homogeneously low CBV while high-grade tumors often showed areas of both high and low CBV. The maximum tumor CBV/white matter ratio was compared between low- (n=3) and high-grade gliomas (n=5) in patients without previous treatment and with histologic verification (n=8) and was significantly higher in high-grade gliomas (9<0.01). High CBV foci in nonenhancing tumor areas mere present in 2 cases. The distinction between radiation necrosis and active tumor could be made correctly in 3 of 4 cases. The information provided by MR CBV mapping has the potential to be an adjunct in the clinical care of glioma patients. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIAT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP ARONEN, HJ (reprint author), HELSINKI UNIV,CENT HOSP,DEPT RADIOL,HAARTMANINKATU 4,SF-00290 HELSINKI,FINLAND. FU FIC NIH HHS [1 F05 TW04520]; NCI NIH HHS [R01-CA40303]; NHLBI NIH HHS [R01-HL39810] NR 29 TC 88 Z9 93 U1 0 U2 6 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD SEP PY 1995 VL 36 IS 5 BP 520 EP 528 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RR600 UT WOS:A1995RR60000013 PM 7640098 ER PT J AU DROUNGAS, A EHRMAN, RN CHILDRESS, AR OBRIEN, CP AF DROUNGAS, A EHRMAN, RN CHILDRESS, AR OBRIEN, CP TI EFFECT OF SMOKING CUES AND CIGARETTE AVAILABILITY ON CRAVING AND SMOKING-BEHAVIOR SO ADDICTIVE BEHAVIORS LA English DT Article ID CONDITIONED ABSTINENCE; NICOTINE ADDICTION; ABUSE PATIENTS; COCAINE ABUSE; RELAPSE; ALCOHOL; REACTIVITY; EXPOSURE; STIMULI; URGES AB This study examined whether smokers respond differently to smoking cues than to affectively neutral or unpleasant cues without smoking content, and whether reactivity is affected by expectations regarding the opportunity to smoke. Expectancy was manipulated by telling subjects in group SMOKE that they could smoke, and subjects in group NO SMOKE that they could not smoke following each cue-reactivity session. The dependent variables were subjective ratings of ''desire to smoke'', ''high'', ''withdrawal'', and mood, as well as latency to initiate smoking measured in group SMOKE. Statistical analyses demonstrated that only group SMOKE (a) reported greater ''desire to smoke'' and ''withdrawal'' to the smoking cues compared to the baseline, (b) reported greater ''desire to smoke'' to the smoking cues than to the unpleasant or to the neutral cues, and (c) smoked faster after the smoking cues than after the neutral cues. Both groups rated the unpleasant cues as affectively more negative than the neutral cues. The data suggest that the impact of drug-cues on craving and subsequent drug-use is due to their drug-related content, and not to negative affect. Furthermore, the impact of drug-related cues appears to be influenced by perceived drug-availability. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP DROUNGAS, A (reprint author), UNIV PENN,TREATMENT RES CTR,3900 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. FU NIDA NIH HHS [DA3008] NR 51 TC 133 Z9 133 U1 3 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD SEP-OCT PY 1995 VL 20 IS 5 BP 657 EP 673 DI 10.1016/0306-4603(95)00029-C PG 17 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA RW891 UT WOS:A1995RW89100010 PM 8712062 ER PT J AU TORCHILIN, VP AF TORCHILIN, VP TI LONG-CIRCULATING DRUG-DELIVERY SYSTEMS - PREFACE SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP TORCHILIN, VP (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR IMAGING & PHARMACEUT RES,149,13TH ST,BOSTON,MA 02129, USA. NR 0 TC 4 Z9 4 U1 0 U2 1 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 SEP PY 1995 VL 16 IS 2-3 BP 125 EP 126 DI 10.1016/0169-409X(95)90007-I PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TD171 UT WOS:A1995TD17100001 ER PT J AU PAPISOV, MI AF PAPISOV, MI TI MODELING IN-VIVO TRANSFER OF LONG-CIRCULATING POLYMERS (2 CLASSES OF LONG CIRCULATING POLYMERS AND FACTORS AFFECTING THEIR TRANSFER IN-VIVO) SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE MACROMOLECULE; POLYMER; COLLOID; PHARMACOKINETICS; IN VIVO TRANSFER; DRUG TARGETING; DRUG DELIVERY; DRUG CARRIER ID LPS-BINDING-PROTEIN; LIPOPOLYSACCHARIDE LPS; FIBRONECTIN STRUCTURE; COMPLEMENT PROTEINS; COVALENT BINDING; RECEPTOR; LECTIN; CELLS; PHAGOCYTOSIS; TRANSCYTOSIS AB The relationships between polymer structure and circulation in vivo are discussed on the basis of a mathematical model of polymer transfer. Significant differences in polymer distribution in liquid compartments allow to divide long-circulating polymers and particulates into two groups, large (non-extravasating) and small (extravasating) polymers. Transfer processes that members of these two groups undergo are distinctively different and can be described by different idealized models. Although polymers of both classes may consist of the same constituents, their in vivo localization in liquid compartments and capability of cooperative interactions with components of biological systems may be essentially different. Therefore, relative impact of polymer structure on biokinetics of large and small polymers may differ. Minimization of polymer clearance due to interactions with biological systems and renal filtration is important in the development of long-circulating polymers. Hydrophilic interface brushes assembled of non-reactive polymer chains proved to be effective in prolongation of circulation of both extravasating and non-extravasating polymers, although prolongation mechanisms may differ. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP PAPISOV, MI (reprint author), MASSACHUSETTS GEN HOSP,CTR MGH NMR,DEPT RADIOL,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 54 TC 19 Z9 19 U1 0 U2 2 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 SEP PY 1995 VL 16 IS 2-3 BP 127 EP 139 DI 10.1016/0169-409X(95)00021-X PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TD171 UT WOS:A1995TD17100002 ER PT J AU TORCHILIN, VP TRUBETSKOY, VS AF TORCHILIN, VP TRUBETSKOY, VS TI WHICH POLYMERS CAN MAKE NANOPARTICULATE DRUG CARRIERS LONG-CIRCULATING SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE LONG-CIRCULATING DRUG CARRIERS; LIPOSOMES; NANOPARTICLES; POLY(ETHYLENE GLYCOL); AMPHIPHILIC FLEXIBLE POLYMERS; POLYMER CONFORMATIONS ID IONIC SURFACTANT POLOXAMER-338; LARGE UNILAMELLAR LIPOSOMES; POLYSTYRENE MICROSPHERES; COLLOIDAL PARTICLES; BLOOD-CIRCULATION; CLEARANCE INVIVO; TARGET BINDING; BONE-MARROW; STABILITY; TIME AB The protective effect of poly(ethylene glycol) and some other polymers on nanoparticulate carriers including liposomes is considered in terms of statistical behavior of macromolecules in solution, when polymer flexibility plays a key role. According to the mechanism proposed, surface-grafted chains of flexible and hydrophilic polymers form dense ''conformational clouds'' preventing other macromolecules from the interaction with the surface even at low concentration of protecting polymer. Using liposomes as an example, experimental evidence is presented of the importance of protecting polymer flexibility in liposome steric protection. Further possible applications of the suggested model are discussed. The possibility of using protecting polymers other than poly(ethylene glycol) is analyzed, and examples of such polymers are given based on polymer-coated liposome biodistribution data. General requirements for protecting polymers are formulated, and differences in steric protection of liposomes and particles are discussed. The scale of protective effect is interpreted as the balance between the energy of hydrophobic anchor interaction with the liposome membrane core or with the particle surface and the energy of polymer chain free motion in solution. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP TORCHILIN, VP (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR IMAGING & PHARMACEUT RES,149,13TH ST,BOSTON,MA 02129, USA. NR 54 TC 304 Z9 311 U1 5 U2 51 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 SEP PY 1995 VL 16 IS 2-3 BP 141 EP 155 DI 10.1016/0169-409X(95)00022-Y PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TD171 UT WOS:A1995TD17100003 ER PT J AU TRUBETSKOY, VS TORCHILIN, VP AF TRUBETSKOY, VS TORCHILIN, VP TI USE OF POLYOXYETHYLENE-LIPID CONJUGATES AS LONG-CIRCULATING CARRIERS FOR DELIVERY OF THERAPEUTIC AND DIAGNOSTIC AGENTS SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE AMPHIPHILIC POLYMER; MICELLE; POLYETHYLENEOXIDE; DRUG CARRIER; LYMPHATIC DELIVERY ID ACID) BLOCK COPOLYMER; MIXED-MICELLES; LIPOSOMES; ABSORPTION; VESICLES; BILAYER; PROLONG; TIMES AB The utilization of micelle forming block-copolymers as long-circulating drug carriers for sparingly soluble or amphiphilic drugs or diagnostic agents is reviewed with the emphasis on the use of phosphatidylethanolamine-polyethyleneoxide (PE-PEO) conjugates as structural amphiphilic polymers for formulation of polymeric micelles. PE-PEO conjugates spontaneously form particles with average diameter 10-30 nm depending on the molecular weight of PEO block and which are stable upon dilution at ambient temperature. Topoisomerase II inhibitor ellipticine was shown to be successfully incorporated into PE-PEO (5 kDa) conjugate micelles in vitro. Percutaneous lymphatic delivery of amphiphilic diagnostic agents incorporated into PE-PEO micelles was demonstrated using magnetic resonance imaging and gamma-scintigraphy. For water-soluble low molecular weight drugs one can expect hydrophobic prodrug approach to be most suitable for use with this drug delivery system. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP TRUBETSKOY, VS (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,149 13TH ST,BOSTON,MA 02129, USA. NR 33 TC 104 Z9 107 U1 2 U2 13 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 SEP PY 1995 VL 16 IS 2-3 BP 311 EP 320 DI 10.1016/0169-409X(95)00032-3 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TD171 UT WOS:A1995TD17100013 ER PT J AU WEISSLEDER, R BOGDANOV, A NEUWELT, EA PAPISOV, M AF WEISSLEDER, R BOGDANOV, A NEUWELT, EA PAPISOV, M TI LONG-CIRCULATING IRON-OXIDES FOR MR-IMAGING SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE IRON OXIDE; MR IMAGING ID CONTRAST AGENTS; ALBUMIN MICROSPHERES; TRANSPORT; MAGNETITE; PARTICLES AB A variety of iron oxide preparations with long blood half-lives have been synthesized for MR imaging. Potential applications of these agents include MR angiography, RES imaging, target specific imaging and neuronal transport imaging. This chapter reviews types of iron oxide and mechanisms that are responsible for a prolonged plasma half-life. C1 OREGON HLTH SCI UNIV,BLOOD BRAIN BARRIER PROGRAM,PORTLAND,OR 97201. RP WEISSLEDER, R (reprint author), MASSACHUSETTS GEN HOSP,MGH NMR CTR,13TH ST,BLDG 149,BOSTON,MA 02129, USA. NR 50 TC 292 Z9 302 U1 2 U2 34 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 SEP PY 1995 VL 16 IS 2-3 BP 321 EP 334 DI 10.1016/0169-409X(95)00033-4 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TD171 UT WOS:A1995TD17100014 ER PT J AU BOGDANOV, A WEISSLEDER, R BRADY, TJ AF BOGDANOV, A WEISSLEDER, R BRADY, TJ TI LONG-CIRCULATING BLOOD-POOL IMAGING AGENTS SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE CONTRAST AGENT; GRAFT COPOLYMER; POLY(ETHYLENE GLYCOL); CHELATE; PARAMAGNETIC; GADOLINIUM ID MACROMOLECULAR CONTRAST AGENT; DTPA-LABELED DEXTRAN; GD-DTPA; MR-ANGIOGRAPHY; MYOCARDIAL-INFARCTION; COVALENT ATTACHMENT; POLYETHYLENE-GLYCOL; TUMOR ANGIOGENESIS; ENHANCING AGENT; GADOLINIUM-DTPA AB Two generally accepted methods are currently in use to ensure to prolong the circulation of imaging agents in an effort to make them suitable for blood pool (vascular) imaging. The first method uses in vivo or ex vivo labeling of blood cells or plasma components with diagnostic labels. The second method employs synthetic (covalently modified) macromolecules, colloids and/or liposomes capable of carrying diagnostic labels. Current blood pool imaging technologies where both methods may be successfully applied include mainly MR, CT and scintigraphy. Medical applications for the use of vascular imaging include cardiovascular disease (stenosis, aneurysm, atherosclerosis, trauma), abnormal capillary permeability (cancer detection, inflammation) and tumor neovascularity (metastatic potential). However, only selected agents are expected to have the potential of being useful for a variety of potential blood pool imaging tasks. We describe here a novel class of grafted macromolecular agents (methoxy poly(ethylene)glycol-succinyl-(N-epsilon-poly(L-lysy l)diethylene) pentaacetamide (MPEG-PL-DTPA)) that fulfills the prerequisites of long blood half-life, exclusive intravascular distribution and low immunogenicity/toxicity. We report physico-chemical and biological properties of these agents as well as their major applications in radiology. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP BOGDANOV, A (reprint author), MASSACHUSETTS GEN HOSP,MGH NMR CTR,MAGNET RESONANCE PHARMACEUT PROGRAM,RM 5416,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 73 TC 49 Z9 52 U1 1 U2 10 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 SEP PY 1995 VL 16 IS 2-3 BP 335 EP 348 DI 10.1016/0169-409X(95)00034-5 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TD171 UT WOS:A1995TD17100015 ER PT J AU WEISSMAN, NJ PALACIOS, IF NIDORF, SM DINSMORE, RE WEYMAN, AE AF WEISSMAN, NJ PALACIOS, IF NIDORF, SM DINSMORE, RE WEYMAN, AE TI 3-DIMENSIONAL INTRAVASCULAR ULTRASOUND ASSESSMENT OF PLAQUE VOLUME AFTER SUCCESSFUL ATHERECTOMY SO AMERICAN HEART JOURNAL LA English DT Article ID DIRECTIONAL CORONARY ATHERECTOMY; INTRACORONARY ULTRASOUND; COMPENSATORY ENLARGEMENT; LUMINAL DIAMETER; ANGIOPLASTY; ARTERIES; VALIDATION; RESTENOSIS; MECHANISMS; DISEASE AB The primary purpose of directional coronary atherectomy is the removal of intraluminal plaque. Angiography allows assessment of residual lumen narrowing but is limited in the assessment of residual plaque burden. Intravascular ultrasound has proven useful in assessing plaque size, but current use has been limited to a single, representative cross-sectional image rather than an evaluation of the entire plaque volume. To determine the volume of residual plaque after angiographically successful directional coronary atherectomy (less than or equal to 20% residual stenosis), we performed intravascular ultrasound in 19 patients before and after atherectomy. Only coronary lesions optimal for three-dimensional analysis (a single, discrete stenosis in a nontortuous, noncalcified native coronary artery) were selected. A 2.9F sheath-design intravascular ultrasound catheter with a motorized pullback device was used in all patients. The cross-sectional area of the artery (defined by the medial-adventitia border), the lumen, and the plaque were measured at 1 mm intervals over a 15 to 20 mm segment, which included the target lesion and a proximal reference segment (n = 362 cross-sections), before and after atherectomy. The volumes of the artery, vessel lumen, and plaque were calculated with a modified Simpson's equation and compared with standard area measurements at the point of maximal stenosis. After directional atherectomy there was no change in the volume of the artery, lumen, or plaque proximal to the target lesion. In contrast, there was a significant increase in luminal volume in the region of the target lesion (67.6 +/- 25.7 mm(3) to 120.7 +/- 47.7 mm(3); p = 0.01) because of a reduction in plaque volume (107.9 +/- 28.2 mm(3) to 65.1 +/- 10.6 mm(3); p = 0.01). On average, 39.7% (range 24% to 56%) of the target plaque volume was removed. The proportion of plaque removed did not relate to atherectomy catheter size or the ratio of catheter size to arterial or lumen size. Although a large percentage of target plaque volume remained, the average residual plaque volume (per millimeter of artery) was similar to the average plaque volume in the proximal reference segment (p not significant). Two-dimensional analysis at the point of maximal stenosis tended to overestimate the effect of the atherectomy (51.7% vs 39.7% of the plaque removed; p < 0.05) because of an overestimation of plaque burden (79.4% of the vessel area vs 61.9% of the vessel volume; p < 0.05) but did provide an adequate postatherectomy assessment of the residual plaque and lumen. Directional coronary atherectomy increases lumen size by decreasing plaque volume without significantly changing arterial size. Despite apparent angiographically documented success, the majority of plaque volume remains after coronary atherectomy. Two-dimensional measurements of plaque, luminal, and arterial area at the site of maximal stenosis may overestimate the atherectomy effect but if appropriately selected can provide an adequate representation of the residual plaque. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIAC ULTRASOUND & CATHETERIZAT LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV CARDIOL,BOSTON,MA 02114. NR 25 TC 24 Z9 24 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 1995 VL 130 IS 3 BP 413 EP 419 DI 10.1016/0002-8703(95)90345-3 PN 1 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RR599 UT WOS:A1995RR59900002 PM 7661054 ER PT J AU HAJJAR, RJ ROSE, GA MADSEN, JC LEVINE, RA DESANCTIS, RW AF HAJJAR, RJ ROSE, GA MADSEN, JC LEVINE, RA DESANCTIS, RW TI EXTRAPERICARDIAL CARDIAC-TAMPONADE AFTER BLUNT CHEST TRAUMA SO AMERICAN HEART JOURNAL LA English DT Note ID MEDIASTINAL HEMATOMA C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 1995 VL 130 IS 3 BP 620 EP 621 DI 10.1016/0002-8703(95)90377-1 PN 1 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RR599 UT WOS:A1995RR59900034 PM 7661086 ER PT J AU LU, ES LIN, TS HARMS, BL GAUMNITZ, EA SINGARAM, C AF LU, ES LIN, TS HARMS, BL GAUMNITZ, EA SINGARAM, C TI A SEVERE CASE OF DIVERSION COLITIS WITH LARGE ULCERATIONS SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Note ID DIFFERENTIAL-DIAGNOSIS; RECTUM; COLON; COLOSTOMY; DISEASE AB Diversion colitis is an inflammatory condition that develops in the excluded segment of colon after surgical diversion. Inflammatory changes include aphthous-type ulcerations, crypt abscesses, and mucosal friability. These features may be seen in other inflammatory diseases of the colon, making diagnosis difficult. Even though symptoms such as cramping pain, bleeding, and mucous discharge have been described with diversion colitis, most cases are asymptomatic. In this article we report a patient who presented with sepsis secondary to severe diversion colitis with several large (2-4 cm in diameter), deep ulcerations and air in the colonic wall, requiring colectomy. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV WISCONSIN,DEPT SURG,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. NR 12 TC 4 Z9 4 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 1995 VL 90 IS 9 BP 1508 EP 1510 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RT775 UT WOS:A1995RT77500028 PM 7661179 ER PT J AU SORENSEN, G HIMMELSTEIN, JS HUNT, MK YOUNGSTROM, R HEBERT, JR HAMMOND, SK PALOMBO, R STODDARD, A OCKENE, JK AF SORENSEN, G HIMMELSTEIN, JS HUNT, MK YOUNGSTROM, R HEBERT, JR HAMMOND, SK PALOMBO, R STODDARD, A OCKENE, JK TI A MODEL FOR WORKSITE CANCER PREVENTION - INTEGRATION OF HEALTH PROTECTION AND HEALTH PROMOTION IN THE WELLWORKS PROJECT SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE CANCER PREVENTION AND CONTROL; WORKSITES; HEALTH PROTECTION; HEALTH PROMOTION; HEALTH EDUCATION; OCCUPATIONAL HEALTH; NUTRITION ID CESSATION; SMOKING AB Objectives. To describe a theoretic approach and rationale for the integration of health protection and health promotion in worksite cancer prevention programs and to describe an intervention study designed to implement this integration. Methods. Twenty-four worksites were recruited to participate in this randomized controlled study. The theoretically based intervention model integrates health promotion and health protection through (1) joint worker-management participation in program planning and implementation, (2) consultation on worksite changes, and (3) educational programs targeting health behavior change. Results. Although the primary purpose of this paper is to describe a theoretic approach to the integration of health promotion and health protection, preliminary results are also noted. In these predominantly manufacturing worksites, many workers faced the double jeopardy of exposures to occupational carcinogens and personal risks such as smoking or poor dietary habits. Production workers' job responsibilities frequently limited their full participation. Barriers to participation were identified early in the project, and strategies were developed to facilitate maximal worker involvement and worksite changes. Conclusions. Lifestyle changes such as smoking cessation or dietary changes may be more effectively promoted among blue collar audiences when programs also encourage management actions to reduce occupational exposures. Public health professionals trained ill health promotion and health protection must work together to effectively address the health concerns of this population. C1 HARVARD UNIV, SCH PUBL HLTH, BOSTON, MA 02115 USA. DEPT PUBL HLTH, OFF NUTR COMMONWEALTH MASSACHUSETTS, BOSTON, MA USA. UNIV MASSACHUSETTS, SCH MED, OCCUPAT HLTH PROGRAM, AMHERST, MA 01003 USA. UNIV MASSACHUSETTS, SCH MED, DIV PREVENT & BEHAV MED, AMHERST, MA 01003 USA. UNIV MASSACHUSETTS, SCH MED, DEPT COMMUNITY & FAMILY MED, AMHERST, MA 01003 USA. UNIV MASSACHUSETTS, SCH MED, WORCESTER, MA USA. UNIV MASSACHUSETTS, DIV PUBL HLTH SCI, AMHERST, MA 01003 USA. RP DANA FARBER CANC INST, DIV CANC EPIDEMIOL & CONTROL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [U01 CA51686] NR 45 TC 45 Z9 45 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0890-1171 EI 2168-6602 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD SEP-OCT PY 1995 VL 10 IS 1 BP 55 EP 62 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA RW125 UT WOS:A1995RW12500013 PM 10155659 ER PT J AU BRUNS, ME FERGUSON, JE BRUNS, DE BURTON, DW BRANDT, DW JUPPNER, H SEGRE, GV DEFTOS, LJ AF BRUNS, ME FERGUSON, JE BRUNS, DE BURTON, DW BRANDT, DW JUPPNER, H SEGRE, GV DEFTOS, LJ TI EXPRESSION OF PARATHYROID HORMONE-RELATED PEPTIDE AND ITS RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN HUMAN AMNION AND CHORION-DECIDUA - IMPLICATIONS FOR SECRETION AND FUNCTION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE PARATHYROID HORMONE-RELATED PROTEIN; PARATHYROID HORMONE PARATHYROID HORMONE-RELATED PEPTIDE RECEPTOR; AMNION; CHORION-DECIDUA ID AVASCULAR HUMAN AMNION; GENE-EXPRESSION; PROTEIN; CALCIUM; RNA; STIMULATION; TRANSPORT; FRAGMENTS; MAGNESIUM; STRETCH AB OBJECTIVE: Our purpose was to define the location and packaging of parathyroid hormone-related peptide in amnion-chorion and the potential target tissues for its action in fetal membranes. STUDY DESIGN: We studied fetal membranes by use of light microscopic immunocytochemistry with three monoclonal antibodies against distinct regions of the parathyroid hormone-related peptide molecule. For electron microscopy immunogold analysis with a monoclonal antibody specific to the 109-141 fragment was used to observe parathyroid hormone-related peptide intracellularly in amnion membrane and in the chorion layers. Multiplex reverse transcriptase-polymerase chain reaction with Southern blotting was used to identify parathyroid hormone/parathyroid hormone-related peptide receptor and control messenger ribonucleic acids in amnion and chorion-decidua. RESULTS: All monoclonal antibodies revealed immunoreactive parathyroid hormone-related peptide in the amniotic epithelial cells and in some fibroblast-like cells embedded in the extracellular matrix of the amnion. Parathyroid hormone-related peptide was also found in the chorion in fibroblast and trophoblast layers and in decidua. Ultrastructurally immunogold particles were evenly distributed throughout the amniotic epithelial cells and were present in apical microvilli and near the basal membranes. Electron microscopy studies of the chorion cytotrophoblast also showed freely dispersed immunogold particles of parathyroid hormone-related peptide with no packaging in secretory granules. Low to undetectable levels of parathyroid hormone/parathyroid hormone-related peptide receptor messenger ribonucleic acid were found in amnion tissue, whereas abundant receptor messenger ribonucleic acid was found in chorion-decidua. CONCLUSIONS: These results suggest the presence of a parathyroid hormone-related peptide paracrine system within the human fetal membranes. C1 UNIV VIRGINIA,DEPT OBSTET & GYNECOL,CHARLOTTESVILLE,VA. UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103. VET ADM MED CTR,SAN DIEGO,CA 92161. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,BOSTON,MA 02115. RP BRUNS, ME (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,BOX 214,CHARLOTTESVILLE,VA 22908, USA. FU NCI NIH HHS [CA49474]; NIAMS NIH HHS [AR15888]; NICHD NIH HHS [R01-HD12335] NR 25 TC 22 Z9 22 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 1995 VL 173 IS 3 BP 739 EP 746 DI 10.1016/0002-9378(95)90333-X PN 1 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA RX497 UT WOS:A1995RX49700012 PM 7573236 ER PT J AU FONG, DS WARRAM, JH AIELLO, LM RAND, LI KROLEWSKI, AS AF FONG, DS WARRAM, JH AIELLO, LM RAND, LI KROLEWSKI, AS TI CARDIOVASCULAR AUTONOMIC NEUROPATHY AND PROLIFERATIVE DIABETIC-RETINOPATHY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MICROALBUMINURIA; MELLITUS; RISK AB PURPOSE: To determine prospectively whether cardiovascular autonomic neuropathy is a risk factor for proliferative diabetic retinopathy. METHODS: A five year follow-up study of 88 diabetic persons was performed at a center providing primary and specialized care for diabetes. Participants were white, insulin dependent patients with diabetes of 15 to 21 years' duration. The primary end point was the presence of proliferative diabetic retinopathy, seen either on fundus photography or ophthalmologic examination. Cardiovascular autonomic neuropathy was measured at baseline by using a standard protocol. RESULTS: Fourteen patients developed proliferative diabetic retinopathy during follow-up. One measure of cardiovascular autonomic neuropathy, the 30:15 ratio, the heart rate variation at the 30th beat compared with that at the 15th beat, was lower among patients with proliferative diabetic retinopathy (P =.0049) The risk of proliferative diabetic retinopathy in patients with an abnormal cardiovascular autonomic neuropathy index was 2.59, although the estimate was not statistically significant because of the small number of patients who developed proliferative diabetic retinopathy. CONCLUSIONS: This study provides prospective evidence that cardiovascular autonomic neuropathy is associated with proliferative diabetic retinopathy. In addition to ocular determinants of proliferative diabetic retinopathy, systemic risk factors also should be considered when examining patients with diabetes mellitus. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BEETHAM EYE INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. JOSLIN DIABET CTR,DIV RES,EPIDEMIOL & GENET SECT,BOSTON,MA 02215. NR 17 TC 14 Z9 17 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 1995 VL 120 IS 3 BP 317 EP 321 PG 5 WC Ophthalmology SC Ophthalmology GA RT931 UT WOS:A1995RT93100005 PM 7661203 ER PT J AU ROSOWSKI, JJ MERCHANT, SN RAVICZ, ME AF ROSOWSKI, JJ MERCHANT, SN RAVICZ, ME TI MIDDLE-EAR MECHANICS OF TYPE-IV AND TYPE-V TYMPANOPLASTY .1. MODEL ANALYSIS AND PREDICTIONS SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Otological-Society CY MAY 07-08, 1994 CL PALM BEACH, FL SP Amer Otol Soc ID COCHLEA; CAT AB An analysis of type IV and type V tympanoplasty procedures was performed using a quantitative model of the acoustic and mechanical properties of the stapes, cochlea, round window shield, and cavum minor air space. Realistic values for the impedance of these structures were determined from anatomic and functional measurements in normal ears. These model values lead to predicted type IV hearing results that match well with the best surgical results over a broad frequency range (125-4000 Hz). A parametric study of alterations in the model impedances reveals that a good hearing result depends on a mobile stapes, proper aeration of the cavum minor air space, and a sufficiently stiff graft shield. Intersubject variations in the cochlear impedance also can have a significant effect on the postsurgical hearing response. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. FU NIDCD NIH HHS [KO8-DC-00088, P01-DC-00119, P01 DC000119] NR 33 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD SEP PY 1995 VL 16 IS 5 BP 555 EP 564 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA RT233 UT WOS:A1995RT23300002 PM 8588660 ER PT J AU MERCHANT, SN ROSOWSKI, JJ RAVICZ, ME AF MERCHANT, SN ROSOWSKI, JJ RAVICZ, ME TI MIDDLE-EAR MECHANICS OF TYPE-IV AND TYPE-V TYMPANOPLASTY .2. CLINICAL ANALYSIS AND SURGICAL IMPLICATIONS SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Otological-Society CY MAY 07-08, 1994 CL PALM BEACH, FL SP Amer Otol Soc ID CAT AB Type IV and type V tympanoplasty operations are simple, robust, and well-established techniques to reconstruct middle ears that have been severely altered by chronic otitis media. In a previous paper, the authors developed a simple four-block physiologic model to describe hearing results after these procedures. This paper presents a comparison of model predictions to hearing results obtained from a detailed retrospective clinical review of 30 type IV and type V procedures. Audiograms predicted by the model and those observed clinically show good agreement over a wide frequency range (500-4000 Hz) and for many different clinical conditions. Thus, this model reliably predicts postsurgical hearing results. The application of quantitative analyses provided by this model permits the formation of a few simple surgical rules that may improve postoperative hearing results. (1) The footplate should be left as mobile as possible (e.g., by covering it with a very thin split-thickness skin graft, as opposed to a fascia graft, which will tend to stiffen it). If the footplate is ankylosed, it should be removed and replaced with a compliant tissue graft, such as fat. (2) The round window acoustic graft shield should be made as stiff as possible. If the shield material used is temporalis fascia, then one should consider using more than one layer, or reinforcing it with cartilage. (3) An attempt should be made to create an aerated cavum minor containing at least 0.03 cc of air. C1 MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. RP MERCHANT, SN (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [P01 DC000119, KO9 DC 00088, P01 DC 00119] NR 17 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD SEP PY 1995 VL 16 IS 5 BP 565 EP 575 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA RT233 UT WOS:A1995RT23300003 PM 8588661 ER PT J AU RAUCH, SD SANMARTIN, JE MOSCICKI, RA BLOCH, KJ AF RAUCH, SD SANMARTIN, JE MOSCICKI, RA BLOCH, KJ TI SERUM ANTIBODIES AGAINST HEAT-SHOCK-PROTEIN-70 IN MENIERES-DISEASE SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; SENSORINEURAL HEARING-LOSS; RHEUMATOID-ARTHRITIS; AUTOANTIBODIES; MEMBER AB Meniere's syndrome of fluctuating sensorineural hearing loss, episodic vertigo, and tinnitus is the clinical presentation resulting from several different pathologic processes. The present study was designed to probe for immunologic factors in Meniere's disease. It has previously been shown that the presence of circulating antibodies against a 68-kD protein detected by Western blot immunoassay of serum from patients with idiopathic, progressive, bilateral sensorineural hearing loss (IPB SNHL) is highly correlated with both activity of disease and corticosteroid responsiveness of the hearing loss. The authors recently have identified the 68-kD protein as heat shock protein 70 (HSP70). This study presents a retrospective review of results of Western blot assays in 30 patients meeting strict AAO-HNS diagnostic criteria for Meniere's disease. Overall, 47% of patients had anti-HSP70 antibodies. When broken down by clinical pattern, anti-HSP70 antibodies were present in 58.8% of bilateral Meniere's disease, 37.5% of contralateral delayed endolymphatic hydrops, and 33.3% of unilateral Meniere's disease with IPB SNHL in the second affected ear. Detection of antibodies to HSP may serve to identify a subset of patients with Meniere's disease in whom immunologic factors have a pathogenic role. C1 HARVARD UNIV,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,GEN MED SERV,CLIN IMMUNOL & ALLERGY UNITS,BOSTON,MA 02114. RP RAUCH, SD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00824] NR 25 TC 47 Z9 50 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD SEP PY 1995 VL 16 IS 5 BP 648 EP 652 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA RT233 UT WOS:A1995RT23300013 PM 8588671 ER PT J AU SUNDAY, ME WILLETT, CG GRAHAM, SA OREFFO, VIC LINNOILA, RI WITSCHI, H AF SUNDAY, ME WILLETT, CG GRAHAM, SA OREFFO, VIC LINNOILA, RI WITSCHI, H TI HISTOCHEMICAL CHARACTERIZATION OF NONNEUROENDOCRINE TUMORS AND NEUROENDOCINE CELL HYPERPLASIA INDUCED IN HAMSTER LUNG BY 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE WITH OR WITHOUT HYPEROXIA SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID NEURO-ENDOCRINE CELLS; MONOCLONAL-ANTIBODIES; FETAL LUNG; K-RAS; DIFFERENTIATION; NEOPLASMS; BOMBESIN; PROLIFERATION; LOCALIZATION; ONCOPROTEIN AB Lung tumors induced by 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK) with or without hyperoxia have frequent K-ras mutations but only rare p53 mutations, suggesting that this may be a model for non-small cell lung cancers, The goals of the present study were (1) to characterize the histopathology of lung tumors induced in hamsters by NNK with or without O-2 and (2) as a corollary, to quantitate the pulmonary neuroendocrine cell hyperplasia in the different treatment groups early and late in the treatment period. Lung tumors induced by NNK with or without O-2 were 71% adenomas, 22% adenocarcinomas, similar to 4% bronchoalveolar carcinomas, and similar to 4% squamous/adenosquamous carcinomas, One-half of all tumors were positive for the Clara cell antigen CC10 and 21% of NNK-induced tumors were mucin positive, compared with 2% of NNK/O-2-induced tumors (P = 0.003), Immunostaining for PGP9.5 was positive in 5% of tumors induced by NNK alone, but in none of NKK/O-2-induced tumors (P = 0.024), Abundant proliferating cell nuclear antigen occurred in 55% of NNK-induced tumors, compared with 19% of NNK/O-2-induced tumors (P = 0.003), These data indicate that NNK with or without O-2 induces non-neuroendocrine lung tumors, Hyperoxia appears to inhibit cell proliferation and suppress mucinous and partial neuroendocrine differentiation in some of these tumors. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. UNIV CALIF DAVIS,INST TOXICOL & ENVIRONM HLTH,DAVIS,CA. NCI,BIOMARKERS & PREVENT RES BRANCH,KENSINGTON,MD. RP SUNDAY, ME (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [R01-HL44984] NR 40 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1995 VL 147 IS 3 BP 740 EP 752 PG 13 WC Pathology SC Pathology GA RU160 UT WOS:A1995RU16000021 PM 7677185 ER PT J AU BORSOOK, D HYMAN, SE AF BORSOOK, D HYMAN, SE TI PROENKEPHALIN GENE-REGULATION IN THE NEUROENDOCRINE HYPOTHALAMUS - A MODEL OF GENE-REGULATION IN THE CNS SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE STRESS; OPIOID; TRANSCRIPTION FACTORS ID CENTRAL NERVOUS-SYSTEM; MESSENGER-RNA LEVELS; RAT ADRENAL-MEDULLA; CORTICOTROPIN-RELEASING HORMONE; HIPPOCAMPAL MOSSY FIBERS; BOVINE CHROMAFFIN CELLS; RIBONUCLEIC-ACID LEVELS; OPIOID-PEPTIDES; GUINEA-PIG; VENTROMEDIAL HYPOTHALAMUS AB During the past decade, a great deal of progress has been made in studying the mechanisms by which transcription of neuropeptides is regulated by second messengers and neural activity. Such investigations, which have depended to a great extent on the use of transformed cell lines, are far from complete. Yet a major challenge for the coming decade is to understand the regulation of neuropeptide genes by physiologically and pharmacologically relevant stimuli in appropriate cell types in vivo. The proenkephalin gene, a member of the opioid gene family, has served as a model to study regulated transcription, not only in cell lines, but also in central (e.g., hypothalamic) and peripheral (e.g., adrenal) neuroendocrine tissues. Here we review regulation of proenkephalin gene expression in the hypothalamus. Several approaches, including in situ hybridization, use of transgenic mice, and the adaptation of electrophoretic mobility shift assays to complex tissues, have played critical roles in recent advances. A summary of possible future developments in this field of research is also presented. C1 HARVARD UNIV, SCH MED, DEPT ANESTHESIA, MOLEC & DEV NEUROSCI LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. FU NIDA NIH HHS [DA-00257, DA-09565, DA-07134] NR 205 TC 33 Z9 33 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 SEP PY 1995 VL 269 IS 3 BP E393 EP E408 PG 16 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA RV599 UT WOS:A1995RV59900001 PM 7573416 ER PT J AU KATO, S SPINALE, FG TANAKA, R JOHNSON, W COOPER, G ZILE, MR AF KATO, S SPINALE, FG TANAKA, R JOHNSON, W COOPER, G ZILE, MR TI INHIBITION OF COLLAGEN CROSS-LINKING - EFFECTS ON FIBRILLAR COLLAGEN AND VENTRICULAR DIASTOLIC FUNCTION SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE DIASTOLE; STIFFNESS ID RAT LEFT-VENTRICLE; HYPERTROPHY; MYOCARDIUM; HYPERTENSION; MUSCLE; DYSFUNCTION; STIFFNESS; FIBROSIS; NETWORK; DISEASE AB The fibrillar collagen network is postulated to be a primary determinant of left ventricular diastolic stiffness. This hypothesis was tested by examining the structural and physiological effects of a reduction in fibrillar collagen content and cross-linking in the intact left ventricle. Collagen cross-linking was inhibited by treating five normal adult pigs with beta-aminopropionitrile (BAPN; 10 g/day po) for 6 wk; five normal untreated pigs served as controls. Left ventricular volume, mass, and function were determined by simultaneous echocardiography and catheterization. Chamber stiffness, defined by pressure vs. volume data, and myocardial stiffness, defined by stress vs. dimension data, were determined from variably loaded beats during dextran infusion. Collagen distribution (% area) and integrity (% confluence) were determined by light microscopy. Collagen content was measured by hydroxyproline assay, and collagen cross-linking was measured by salt extraction. BAPN decreased collagen distribution (% area decreased from 12 +/- 1% in control to 7 +/- 1% in BAPN, P < 0.05), collagen integrity (% confluence decreased from 8 +/- 1% in control to 4 +/- 1% in BAPN, P < 0.05), collagen content (from 36 +/- 2 mg/g dry wt in control to 27 +/- 2 mg/g dry wt in BAPN, P < 0.05), and collagen cross-linking (extractable collagen increased from 21 +/- 2% in control to 28 +/- 2% in BAPN, P < 0.05). BAPN decreased chamber stiffness (0.13 +/- 0.02 in control to 0.06 +/- 0.01 in BAPN, P < 0.05) and myocardial stiffness (10.4 +/- 0.5 in control to 6.6 +/- 0.5 in BAPN, P < 0.05). Thus BAPN inhibited collagen cross-linking, decreased total collagen, and disrupted collagen distribution and integrity. These changes in the fibrillar collagen network resulted in a reduction in chamber and myocardial stiffness. These findings provide evidence to suggest that the fibrillar collagen matrix is a primary determinant of left ventricular diastolic stiffness in the normal heart. C1 MED UNIV S CAROLINA, DEPT MED, DIV CARDIOL, GAZES CARDIAC RES INST, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT SURG, DIV CARDIOTHORAC SURG, CHARLESTON, SC 29425 USA. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29425 USA. FU NHLBI NIH HHS [HL-45024] NR 31 TC 79 Z9 80 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1995 VL 269 IS 3 BP H863 EP H868 PG 6 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA RV400 UT WOS:A1995RV40000016 PM 7573529 ER PT J AU FARAONE, SV KREMEN, WS LYONS, MJ PEPPLE, JR SEIDMAN, LJ TSUANG, MT AF FARAONE, SV KREMEN, WS LYONS, MJ PEPPLE, JR SEIDMAN, LJ TSUANG, MT TI DIAGNOSTIC-ACCURACY AND LINKAGE ANALYSIS - HOW USEFUL ARE SCHIZOPHRENIA SPECTRUM PHENOTYPES SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID JERUSALEM INFANT-DEVELOPMENT; GENETICALLY COMPLEX TRAITS; DSM-III; PSYCHIATRIC-DISORDERS; PERSONALITY-DISORDERS; EYE-TRACKING; RELATIVES; CHILDREN; PARENTS; PROBANDS AB Objective: Numerous studies suggest that the nonschizophrenic relatives of schizophrenic patients exhibit psychiatric and other features that discriminate them from normal comparison subjects. These features Gave been put forth as ''spectrum'' phenotypes that may be variant manifestations of the schizophrenia genotype. However, most of these studies do not address a key measurement question: does the diagnostic accuracy of these spectrum classifications warrant their use in genetic linkage studies of schizophrenia? Method: The authors reviewed 30 studies of putative indicators of the schizophrenic genotype: schizotypal personality disorder, eye tracking dysfunction, attentional impairment, auditory evoked potentials, neurological signs, neuropsychological impairment, and allusive thinking. Results: Although each of 42 measures of these indicators discriminated the relatives of schizophrenic patients from the normal comparison subjects, a diagnostic accuracy analysis suggested that only six of these would improve the informativeness of genetic linkage data. Conclusions: Many proposed spectrum phenotypes for schizophrenia may not be useful for linkage analysis because of high false positive rates (poor specificity). Future work aimed at describing and developing phenotypes for linkage analysis should assess the diagnostic accuracy of proposed measures. C1 HARVARD UNIV,MASSACHUSETTS MENTAL HLTH CTR,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. HARVARD UNIV,INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. BOSTON UNIV,DEPT PSYCHOL,BOSTON,MA 02215. RI Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-41874, MH-43518, MH-46318] NR 63 TC 111 Z9 111 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1995 VL 152 IS 9 BP 1286 EP 1290 PG 5 WC Psychiatry SC Psychiatry GA RT231 UT WOS:A1995RT23100010 PM 7653682 ER PT J AU SUGIMORI, T COOLEY, J HOIDAL, JR REMOLDODONNELL, E AF SUGIMORI, T COOLEY, J HOIDAL, JR REMOLDODONNELL, E TI INHIBITORY PROPERTIES OF RECOMBINANT HUMAN MONOCYTE NEUTROPHIL ELASTASE INHIBITOR SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-2; LEUKOCYTE PROTEASE INHIBITOR; AMINO-ACID SEQUENCE; POLYMORPHONUCLEAR LEUKOCYTE; PROTEINASE-INHIBITORS; CYSTIC-FIBROSIS; CATHEPSIN-G; CELL LINE; MACROPHAGES; EXPRESSION AB Human monocyte/neutrophil elastase inhibitor (HEI) is a serpin superfamily protein that rapidly and irreversibly inhibits neutrophil and pancreatic elastase. We generated a recombinant baculovirus that supports production of HEI in insect cells at approximately 400 times the level in monocytes. Recombinant HEI was found to be indistinguishable from monocyte HEI in its physicochemical properties and ability to inhibit neutrophil elastase and pancreatic elastase, The recombinant protein was used to test for additional functions. HEI was shown to inhibit proteinase 3, an important neutrophil inflammatory protease, by the classical serpin mechanism of forming a covalent protease-protease inhibitor complex. Preliminary evidence suggests that HEI also inhibits neutrophil cathepsin G. On the ether hand, HEI does not inhibit u-plasminogen activator (urokinase). These findings suggest that HEI functions as a class-specific regulator of the neutrophil serine proteases characteristically found at inflammatory sites. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. UNIV UTAH,MED CTR,DEPT PULM MED,SALT LAKE CITY,UT 84112. FU NHLBI NIH HHS [HL37615, HL41579] NR 44 TC 30 Z9 30 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 1995 VL 13 IS 3 BP 314 EP 322 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA RT225 UT WOS:A1995RT22500009 PM 7654387 ER PT J AU HOLLISTER, MS MACK, LA PATTEN, RM WINTER, TC MATSEN, FA VEITH, RR AF HOLLISTER, MS MACK, LA PATTEN, RM WINTER, TC MATSEN, FA VEITH, RR TI ASSOCIATION OF SONOGRAPHICALLY DETECTED SUBACROMIAL/SUBDELTOID BURSAL EFFUSION AND INTRAARTICULAR FLUID WITH ROTATOR CUFF TEAR SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SHOULDER; TENDON; US AB OBJECTIVE. Although an association between sonographically detected joint fluid and rotator cuff disease has been reported, the significance of sonographically detected subacromial/subdeltoid bursal effusion has not been studied. We examined a group of patients who had shoulder sonography and surgery to determine the association between bursal and joint effusion and surgically proved tears of the rotator cuff. MATERIALS AND METHODS. We retrospectively reviewed the preoperative shoulder sonography reports of 163 patients for the presence of fluid within the subacromial/subdeltoid bursa or glenohumeral joint. Surgical reports were obtained to determine the status of the rotator cuff. The sonographic reports of 232 asymptomatic shoulders were also reviewed to determine the prevalence of fluid within the subacromial/subdeltoid bursa or the glenohumeral joint. RESULTS. Sixty-seven (41%) of the 163 patients had a joint effusion, bursal fluid, or both, Joint effusion alone was seen in 35 patients. Fourteen of these had a normal rotator cuff at surgery, and 21 had a rotator cuff tear (sensitivity, 22%; specificity, 79%; positive predictive value, 60%), Bursal fluid alone was seen in 10 patients, seven of whom had a rotator cuff tear (sensitivity, 7%; specificity, 96%; positive predictive value, 70%), In 22 patients, fluid was seen in both the bursa and the joint; 21 had surgically proved rotator cuff tears (sensitivity, 22%; specificity, 99%; positive predictive value, 95%). Of the 232 asymptomatic shoulders, 16 (6.9%) had isolated joint effusions, eight (3.4%) had isolated bursal effusions, and four (1.7%) had both joint and bursal effusions. CONCLUSION. The sonographic finding of intraarticular fluid alone (without bursal fluid) has both a low sensitivity and a low specificity for the diagnosis of rotator cuff tears. However, the finding of fluid in the subacromial/subdeltoid bursa, especially when combined with a joint effusion, is highly specific and has a high positive predictive value for associated rotator cuff tears, Sonographically detected fluid in both the joint and the bursa is an uncommon finding in asymptomatic shoulders, The sonographic observation of fluid in the subacromial bursa, either isolated or combined with a joint effusion, should prompt a careful evaluation of the supraspinatus tendon for tear. C1 UNIV WASHINGTON,CTR MED,DEPT RADIOL,SEATTLE,WA 98195. UNIV WASHINGTON,MED CTR,DEPT ORTHOPED,SEATTLE,WA 98195. RP HOLLISTER, MS (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT RADIOL,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 15 TC 78 Z9 83 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1995 VL 165 IS 3 BP 605 EP 608 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RQ006 UT WOS:A1995RQ00600021 PM 7645478 ER PT J AU BROWN, JH STALLMEYER, MJB LUSTRIN, ES CHEW, FS AF BROWN, JH STALLMEYER, MJB LUSTRIN, ES CHEW, FS TI PRIMARY CEREBRAL LYMPHOMA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID MR C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 3 TC 5 Z9 5 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1995 VL 165 IS 3 BP 626 EP 626 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RQ006 UT WOS:A1995RQ00600025 PM 7645482 ER PT J AU HAYMAN, LA MATURI, RK PFLEGER, MJ DIAZMARCHAN, P HOROWTIZ, B TANG, RA SOPARKAR, CNS PATRINELY, JR AF HAYMAN, LA MATURI, RK PFLEGER, MJ DIAZMARCHAN, P HOROWTIZ, B TANG, RA SOPARKAR, CNS PATRINELY, JR TI MR-IMAGING OF THE EYELIDS - NORMAL AND PATHOLOGICAL FINDINGS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ANATOMY AB MR imaging is commonly used to evaluate orbital and facial soft-tissue disease. Although the eyelids are visible on these images, the radiographic appearance and the detailed anatomy of these structures has received little attention in the literature [1-4]. Anatomic correlation with MR images may be extremely helpful in the accurate interpretation and staging of eyelid malignancies and infections. C1 BAYLOR COLL MED,HERBERT J FRENSLEY CTR IMAGING RES,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT OPHTHALMOL,HOUSTON,TX 77030. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. UNIV TEXAS,MED BRANCH,DEPT OPHTHALMOL,GALVESTON,TX 77555. RP HAYMAN, LA (reprint author), BAYLOR COLL MED,DEPT RADIOL,HOUSTON,TX 77030, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1995 VL 165 IS 3 BP 639 EP 644 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RQ006 UT WOS:A1995RQ00600028 PM 7645485 ER PT J AU FANBURG, JC MEISKINDBLOM, JM ROSENBERG, AE AF FANBURG, JC MEISKINDBLOM, JM ROSENBERG, AE TI MULTIPLE ENCHONDROMAS ASSOCIATED WITH SPINDLE-CELL HEMANGIOENDOTHELIOMAS - AN OVERLOOKED VARIANT OF MAFFUCCIS-SYNDROME SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE MAFFUCCIS SYNDROME; SPINDLE-CELL HEMANGIOENDOTHELIOMAS; ENCHONDROMAS; SPLEEN; CAVERNOUS HEMANGIOMA ID ANGIOSARCOMA; HEMANGIOMA AB Maffucci's syndrome is classically defined as the association of multiple enchondromas and hemangiomas. Spindle-cell hemangioendothelioma (SCH), a recently described vascular tumor of purported low malignant potential, has both cavernous hemangioma and Kaposi-like features. We report six patients with Maffucci's syndrome in whom all vascular lesions were SCH. The enchondromas involved the small and long tubular bones of the extremities in all of these patients; flat bones were also involved in three patients. The SCH usually arose in the extremities, distal to the knees and elbows. Five of the six patients had multiple and separate nodules of SCH, and in four patients there was recurrent or persistent SCH within 6 months to 4 years after initial removal. One patient also had a vascular tumor in the spleen mainly with features of a low-grade angiosarcoma with separate SCH-like foci. None of the SCH have metastasized within a follow-up period averaging 20 years. Five patients are alive 14 to 31 years after presentation. One patient died from metastatic dedifferentiated chondrosarcoma. The patient with the low-grade splenic angiosarcoma is alive approximately 2 years after diagnosis, Reappraisal of the older literature suggests that some of the vascular tumors occurring in Maffucci's syndrome, previously diagnosed as hemangiomas, may in fact be SCH, The apparent association between Maffucci's syndrome and SCH, the presence of SCH in other congenital syndromes, and the young patient age and multicentric distribution of SCH unassociated with Maffucci's syndrome raise the possibility that SCH may be a manifestation of a congenital mesodermal disorder with a genetic background related to Maffucci's syndrome. Although the behavior of SCH appears to be one of a locally recurrent or persistent multicentric lesion that does not metastasize, the association of SCH-like foci in a low-grade angiosarcoma of the spleen raises the possibility that SCH may rarely be associated with a higher grade lesion. SCH, at least in the setting of Maffucci's syndrome, should be carefully monitored. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. ARMED FORCES INST PATHOL,DEPT SOFT TISSUE PATHOL,WASHINGTON,DC. NR 37 TC 29 Z9 29 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 1995 VL 19 IS 9 BP 1029 EP 1038 DI 10.1097/00000478-199509000-00006 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA RQ384 UT WOS:A1995RQ38400006 PM 7661276 ER PT J AU DERSHWITZ, M RANDEL, GI ROSOW, CE FRAGEN, RJ CONNORS, PM LIBROJO, ES SHAW, DL PENG, AW JAMERSON, BD AF DERSHWITZ, M RANDEL, GI ROSOW, CE FRAGEN, RJ CONNORS, PM LIBROJO, ES SHAW, DL PENG, AW JAMERSON, BD TI INITIAL CLINICAL-EXPERIENCE WITH REMIFENTANIL, A NEW OPIOID METABOLIZED BY ESTERASES SO ANESTHESIA AND ANALGESIA LA English DT Article ID PHARMACOKINETICS; GI87084B; SURGERY AB Remifentanil is a new, esterase-metabolized opioid for anesthesia. Nonspecific esterases terminate the drug effect, with a context-sensitive half-time which plateaus at 3-4 min. This dose-ranging pilot study was designed to estimate the dose requirement of remifentanil for abolition of the responses to skin incision and intraoperative stimuli, and to determine the speed of recovery. Fifty-one unpremedicated patients took part at two centers. Anesthesia was induced with propofol, 67% nitrous oxide, and vecuronium. Remifentanil was then given (1 mu g/kg, plus an infusion of 0.0125-1.0 mu g . kg(-1). min(-1)). Responses were defined as: >15% increase in systolic blood pressure or >20% increase in heart rate, tearing, sweating, movement, or coughing. Responses to incision or surgery were treated with 0.5 mu g/kg remifentanil boluses and a 50% increase in infusion rate, which could be done twice. Subsequent responses were treated with propofol or isoflurane. Remifentanil and nitrous oxide administration were terminated after the incision was closed. ED50 for response to skin incision varied between the two study sites (0.020 and 0.087 mu g . kg(-1). min(-1)). ED50 for response to all surgical stimuli was 0.52 mu g . kg(-1). min(-1). At 0.3 mu g . kg(-1). min(-1) or more, only 3 of 21 patients required isoflurane. Recovery was not longer in patients receiving larger doses to spontaneous ventilation (2.5-4.6 min), tracheal extubation (4.2-7.0 min), and response to verbal command (3.0-4.6 min). Postoperative pain was reported in most patients (92%) at a median time of 21 min. We conclude that remifentanil was effective and well tolerated as a component of nitrous oxide-opioid-relaxant anesthesia. Over the 80-fold range of infusion rates given, patients awoke, breathed, and were tracheally extubated within a few minutes. C1 HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02115. NORTHWESTERN UNIV,CHICAGO,IL 60611. NORTHWESTERN MEM HOSP,DEPT ANESTHESIA,CHICAGO,IL. GLAXO INC,RES INST,RES TRIANGLE PK,NC 27709. RP DERSHWITZ, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 9 TC 86 Z9 96 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 1995 VL 81 IS 3 BP 619 EP 623 DI 10.1097/00000539-199509000-00035 PG 5 WC Anesthesiology SC Anesthesiology GA RR780 UT WOS:A1995RR78000035 PM 7653833 ER PT J AU PARGGER, H KAUFMANN, MA SCHOUTEN, R WELCH, CA DROP, LJ AF PARGGER, H KAUFMANN, MA SCHOUTEN, R WELCH, CA DROP, LJ TI HEMODYNAMIC-RESPONSES TO ELECTROCONVULSIVE-THERAPY IN A PATIENT 5 YEARS AFTER CARDIAC TRANSPLANTATION SO ANESTHESIOLOGY LA English DT Note DE BLOOD PRESSURE, HYPERTENSION; ELECTROCONVULSIVE THERAPY; HEART, CATECHOLAMINE SUPERSENSITIVITY DENERVATION ID DENERVATED HUMAN HEART; SUPERSENSITIVITY; NOREPINEPHRINE; CONTRACTILITY C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 15 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3 BP 625 EP 627 DI 10.1097/00000542-199509000-00025 PG 3 WC Anesthesiology SC Anesthesiology GA RT889 UT WOS:A1995RT88900027 PM 7661366 ER PT J AU ALIKHANI, S BROWN, E ZASLAVSKY, A AF ALIKHANI, S BROWN, E ZASLAVSKY, A TI A STATISTICAL-METHOD FOR PREDICTING ASA STATUS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A33 EP A33 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500033 ER PT J AU CROSBY, G HASAN, A ABE, K STANDAERT, DG AF CROSBY, G HASAN, A ABE, K STANDAERT, DG TI SUBARACHNOID ADMINISTRATION OF AN ANTISENSE OLIGODEOXYNUCLEOTIDE TO THE NMDA-R1 SUBUNIT GENE MODULATES NOCICEPTION IN RATS SO ANESTHESIOLOGY LA English DT Meeting Abstract ID RECEPTOR C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A767 EP A767 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500767 ER PT J AU CULLEN, DJ SWEITZER, BJ EDMONDSON, A BATES, DW LEAPE, LL AF CULLEN, DJ SWEITZER, BJ EDMONDSON, A BATES, DW LEAPE, LL TI EPIDEMIOLOGY OF PREVENTABLE ADVERSE DRUG EVENTS IN MEDICAL AND SURGICAL INTENSIVE-CARE UNITS COMPARED TO GENERAL CARE UNITS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH PUBL HLTH,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH PUBL HLTH,BOSTON,MA 02114. NR 1 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A214 EP A214 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500214 ER PT J AU DAVISON, JK ICHINOSE, F CAMBRIA, RP COLUMBIA, MA AF DAVISON, JK ICHINOSE, F CAMBRIA, RP COLUMBIA, MA TI EFFECTIVE REGIONAL SPINAL-CORD COOLING VIA AN EPIDURAL INFUSION IN ANESTHETIZED SHEEP SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANES & SURG,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A673 EP A673 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500673 ER PT J AU FAHMY, NR AF FAHMY, NR TI CHANGES IN ARTERIAL BLOOD-GASES, END-TIDAL CO2 AND CIRCULATORY VARIABLES ASSOCIATED WITH REMOVAL OF CEMENT DURING REVISION OF TOTAL HIP-ARTHROPLASTY A COMPARISON OF 3 TECHNIQUES SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A1113 EP A1113 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68501113 ER PT J AU FAHMY, NR SUNDER, N PATEL, D AF FAHMY, NR SUNDER, N PATEL, D TI MYOCARDIAL-ISCHEMIA ASSOCIATED WITH TOURNIQUET USE IN LOWER-EXTREMITY SURGERY IN PATIENTS WITH CARDIOVASCULAR-DISEASE SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ORTHOPAED SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A1078 EP A1078 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68501078 ER PT J AU GLASS, P GAN, TJ SEBEL, PS ROSOW, C KEARSE, L BLOOM, M MANBERG, P AF GLASS, P GAN, TJ SEBEL, PS ROSOW, C KEARSE, L BLOOM, M MANBERG, P TI COMPARISON OF THE BISPECTRAL INDEX (BIS) AND MEASURED DRUG CONCENTRATIONS FOR THE MONITORING EFFECTS OF PROPOFOL, MIDAZOLAM, ALFENTANIL AND ISOFLURANE SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 DUKE UNIV,DEPT ANESTHESIOL,DURHAM,NC 27706. EMORY UNIV,DEPT ANESTHESIOL,ATLANTA,GA 30322. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02115. UNIV PITTSBURGH,DEPT ANESTHESIOL,PITTSBURGH,PA. ASPECT MED SYST,DEPT ANESTHESIOL,NATICK,MA. NR 2 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A374 EP A374 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500374 ER PT J AU HANNALLAH, R DAVIS, PJ ORR, R FERRARI, L RIMAR, S AF HANNALLAH, R DAVIS, PJ ORR, R FERRARI, L RIMAR, S TI PROPHYLACTIC ADMINISTRATION OF ONDANSETRON EFFECTIVELY DECREASES POSTOPERATIVE EMESIS IN CHILDREN SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. CHILDRENS HOSP PITTSBURGH,PITTSBURGH,PA 15213. CHILDRENS HOSP & MED CTR,SEATTLE,WA 98105. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A1177 EP A1177 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68501177 ER PT J AU ICHINOSE, F HUANG, PL ZAPOL, WM AF ICHINOSE, F HUANG, PL ZAPOL, WM TI EFFECTS OF NITRO(G)-L-ARGININE METHYLESTER AND KETAMINE ON THE THRESHOLD FOR ISOFLURANE ANESTHESIA IN THE MICE WITH TARGETED NEURONAL NITRIC-OXIDE SYNTHASE GENE DISRUPTION SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,DEPT ANAESTHESIA & MED,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A771 EP A771 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500771 ER PT J AU KEARSE, L ROSOW, C SEBEL, P BLOOM, M GLASS, P HOWELL, S GREENWALD, S AF KEARSE, L ROSOW, C SEBEL, P BLOOM, M GLASS, P HOWELL, S GREENWALD, S TI THE BISPECTRAL INDEX CORRELATES WITH SEDATION HYPNOSIS AND RECALL - COMPARISON USING MULTIPLE AGENTS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIOL,BOSTON,MA. EMORY UNIV,DEPT ANESTHESIOL,ATLANTA,GA 30322. DUKE UNIV,DEPT ANESTHESIOL,DURHAM,NC. UNIV PITTSBURGH,DEPT ANESTHESIOL,PITTSBURGH,PA. ASPECT MED SYST INC,NATICK,MA. NR 1 TC 18 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A507 EP A507 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500507 ER PT J AU KEARSE, L ROSOW, C CONNORS, P DENMAN, W DERSHWITZ, M AF KEARSE, L ROSOW, C CONNORS, P DENMAN, W DERSHWITZ, M TI PROPOFOL SEDATION HYPNOSIS AND BISPECTRAL EEG-ANALYSIS IN VOLUNTEERS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 0 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A506 EP A506 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500506 ER PT J AU LIU, LMP LI, CY DAMIANIRIVERA, JA THURSTON, TA ZASLAVSKY, AM AF LIU, LMP LI, CY DAMIANIRIVERA, JA THURSTON, TA ZASLAVSKY, AM TI CAN CUFFED ENDOTRACHEAL-TUBES BE USED ROUTINELY IN ANESTHETIZED CHILDREN SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A1185 EP A1185 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68501185 ER PT J AU MARTYN, JAJ YANEZ, P ITANI, M AF MARTYN, JAJ YANEZ, P ITANI, M TI POTASSIUM CHANNELS IN THE HYPERKALEMIC RESPONSE TO SUCCINYLCHOLINE SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIOL,BOSTON,MA. SHRINERS BURNS INST,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A905 EP A905 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500905 ER PT J AU MARTYN, JAJ SHI, Y NGUYEN, VN STORELLA, RJ AF MARTYN, JAJ SHI, Y NGUYEN, VN STORELLA, RJ TI CYTOKINES DO NOT ACUTELY AFFECT NEUROMUSCULAR-TRANSMISSION SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. MED COLL PENN,PHILADELPHIA,PA 19129. HAHNEMANN UNIV,PHILADELPHIA,PA 19102. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A271 EP A271 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500271 ER PT J AU OGATA, M FLETCHER, M LOISELLE, P VERMEULEN, MW WARREN, S AF OGATA, M FLETCHER, M LOISELLE, P VERMEULEN, MW WARREN, S TI THE EFFECT OF ANTICOAGULANTS ON LPS BINDING AND NEUTRALIZING BY CAP18 OR CAP18-IGG SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PULM UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A247 EP A247 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500247 ER PT J AU RAINES, DE AF RAINES, DE TI DISSIMILAR ACTIVITIES OF ANESTHETIC AND NONANESTHETIC HALOGENATED, VOLATILE COMPOUNDS ON NICOTINIC ACETYLCHOLINE-RECEPTOR DESENSITIZATION KINETICS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A1260 EP A1260 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68501260 ER PT J AU ROSOW, C KEARSE, L CONNORS, P AF ROSOW, C KEARSE, L CONNORS, P TI AIRWAY-OBSTRUCTION DURING PROPOFOL SEDATION IN VOLUNTEERS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A1086 EP A1086 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68501086 ER PT J AU SCHWEITZER, MP HARRINGTON, BE KRINER, SJ ROBINSON, TA ROLLINS, RJ WILMOUTH, RJ AF SCHWEITZER, MP HARRINGTON, BE KRINER, SJ ROBINSON, TA ROLLINS, RJ WILMOUTH, RJ TI REDUCED PATIENT CHARGES ASSOCIATED WITH EXTUBATION IN LESS-THAN 6 HOURS FOLLOWING CARDIAC-SURGERY SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 DEACONESS MED CTR,BILLINGS,MT 59107. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A221 EP A221 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500221 ER PT J AU SORIANO, S SULLIVAN, L MARTYN, J AF SORIANO, S SULLIVAN, L MARTYN, J TI PHARMACOKINETICS AND PHARMACODYNAMICS OF VECURONIUM IN CHILDREN ON ANTICONVULSANT DRUGS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A167 EP A167 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500167 ER PT J AU TEPLICK, R LOWENSTEIN, E AF TEPLICK, R LOWENSTEIN, E TI THERE IS NO PROVEN BENEFIT OF DELAYING SURGERY FOR 3 TO 6 MONTHS FOLLOWING A MYOCARDIAL-INFARCTION SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. BETH ISRAEL HOSP,BOSTON,MA 02215. NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1995 VL 83 IS 3A SU S BP A122 EP A122 PG 1 WC Anesthesiology SC Anesthesiology GA RX685 UT WOS:A1995RX68500122 ER PT J AU BEAL, MF AF BEAL, MF TI AGING, ENERGY, AND OXIDATIVE STRESS IN NEURODEGENERATIVE DISEASES SO ANNALS OF NEUROLOGY LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; SUPEROXIDE-DISMUTASE ACTIVITY; TOXIN 3-NITROPROPIONIC ACID; AGE-ASSOCIATED ACCUMULATION; MITOCHONDRIAL-DNA DELETION; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; CYTOCHROME-OXIDASE; EXCITOTOXIC LESIONS; NITRIC-OXIDE AB The etiology of neurodegenerative diseases remains enigmatic; however, evidence for defects in energy metabolism, excitotoxicity, and for oxidative damage is increasingly compelling. It is likely that there is a complex interplay between these mechanisms. A defect in energy metabolism may lead to neuronal depolarization, activation of N-methyl-D-aspartate excitatory amino acid receptors, and increases in intracellular calcium, which are buffered by mitochondria. Mitochondria are the major intracellular source of free radicals, and increased mitochondrial calcium concentrations enhance free radical generation. Mitochondrial DNA is particularly susceptible to oxidative stress, and there is evidence of age-dependent damage and deterioration of respiratory enzyme activities with normal aging. This may contribute to the delayed onset and age dependence of neurodegenerative diseases. There is evidence for increased oxidative damage to macromolecules in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease. Potential therapeutic approaches include glutamate release inhibitors, excitatory amino acid antagonists, strategies to improve mitochondrial function, free radical scavengers, and trophic factors. All of these approaches appear promising in experimental studies and are now being applied to human studies. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP BEAL, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,NEUROL SERV,WARREN 408,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS16367, NS31579, NS32365] NR 117 TC 1020 Z9 1050 U1 14 U2 101 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1995 VL 38 IS 3 BP 357 EP 366 DI 10.1002/ana.410380304 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RU333 UT WOS:A1995RU33300003 PM 7668820 ER PT J AU MUI, S REBECK, GW MCKENNAYASEK, D HYMAN, BT BROWN, RH AF MUI, S REBECK, GW MCKENNAYASEK, D HYMAN, BT BROWN, RH TI APOLIPOPROTEIN-E EPSILON-4 ALLELE IS NOT ASSOCIATED WITH EARLIER AGE AT ONSET IN AMYOTROPHIC-LATERAL-SCLEROSIS SO ANNALS OF NEUROLOGY LA English DT Note ID ALZHEIMERS-DISEASE; SUPEROXIDE-DISMUTASE; TYPE-4 ALLELE; E GENOTYPE; FREQUENCY; PROTEIN AB Apolipoprotein E allele 4 (ape E epsilon 4) is known to be in genetic disequilibrium with Alzheimer's disease and is associated with an earlier age at onset of dementia. Whether apo E epsilon 4 is a specific risk factor for Alzheimer's disease or is a more general susceptibility factor that shifts the age at onset of neurodegenerative diseases to earlier ages is unknown. To test these possibilities, we determined the apolipoprotein E genotypes of subjects with familial or sporadic amyotrophic lateral sclerosis (ALS). ApoE allele frequencies of the apoE gene of the ALS subjects (n = 170, epsilon 2 = 0.071, epsilon 3 = 0.771, epsilon 4 = 0.159) were found to be comparable to the allele frequencies of the general population. Furthermore, no significant association was observed between the age at onset or the duration of ALS and the inheritance of apoE epsilon 4: subjects with at least one copy of epsilon 4 (sporadic ALS: n = 15, onset at 57.7 +/- 13.9 years; familial ALS: n = 23, onset at 53.6 +/- 9.5 years, duration [n = 14] of 2.6 +/- 1.6 years) had comparable ages at onset and durations to subjects without epsilon 4 (sporadic ALS: n = 28, onset at 53.1 +/- 17.0 years; familial ALS: n = 56, onset at 50.8 +/- 12.1 years, duration [n = 30] of 1.9 +/- 0.8 years). The lack of association of apoE epsilon 4 with the age at onset and the duration of ALS suggests that apoE epsilon 4 does not have a global effect on the pathogenesis of other neurodegenerative diseases. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DAY NEUROMUSCULAR RES CTR,BOSTON,MA 02114. FU NIA NIH HHS [AG05134, AG12406]; NINDS NIH HHS [NS31248] NR 26 TC 57 Z9 58 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1995 VL 38 IS 3 BP 460 EP 463 DI 10.1002/ana.410380318 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RU333 UT WOS:A1995RU33300017 PM 7668834 ER PT J AU MAYER, RJ AF MAYER, RJ TI SUMMARY OF THE 2ND INTERNATIONAL-CONFERENCE ON BIOLOGY, PREVENTION AND TREATMENT OF GASTROINTESTINAL MALIGNANCIES SO ANNALS OF ONCOLOGY LA English DT Editorial Material DE GASTRIC; PANCREATIC; ANAL; HEPATOCELLULAR; ESOPHAGEAL AND COLORECTAL CARCINOMAS RP MAYER, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 1995 VL 6 IS 7 BP 645 EP 649 PG 5 WC Oncology SC Oncology GA TA129 UT WOS:A1995TA12900009 PM 8664184 ER PT J AU TANABE, KK AF TANABE, KK TI CELL-ADHESION IN TUMOR INVASION SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID SUPPRESSOR; GENE RP TANABE, KK (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,COX 626,BOSTON,MA 02114, USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD SEP PY 1995 VL 2 IS 5 BP 376 EP 377 DI 10.1007/BF02306368 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA RR244 UT WOS:A1995RR24400002 PM 7496830 ER PT J AU EICHBAUM, QG HUGHES, EJ EPSTEIN, JE BEATTY, DW AF EICHBAUM, QG HUGHES, EJ EPSTEIN, JE BEATTY, DW TI RHEUMATIC-FEVER - AUTOANTIBODIES AGAINST A VARIETY OF CARDIAC, NUCLEAR, AND STREPTOCOCCAL ANTIGENS SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID DISEASE; MYOSIN; HEART; ANTIBODIES; PROTEINS; MICE AB Objective-To measure antibody titres to cardiac, nuclear, and streptococcal antigens in different groups of rheumatic fever (n = 60) and control subjects (n = 80) with the aim of identifying cross reactive antigens of potential laboratory diagnostic value. Methods-Enzyme linked immunosorbent assays (ELISA), immunocytochemical, and electrophoretic techniques were used to measure titres of antibodies to a variety of cardiac, nuclear, and streptococcal antigens in seven groups comprising patients with rheumatic fever and control subjects. Results-Increased concentrations of antibodies to several streptococcal and cardiac antigens, in addition to increased IgA and IgG levels, were noted in sera from patients with acute rheumatic fever and chronic rheumatic heart disease. Autoantibodies to nuclear antigens were evident in three rheumatic fever sera. Conclusion-Although we were unable to identify any unique cross reactivity between cardiac and streptococcal antigens, these results demonstrate that there is an exaggerated humoral response to several cardiac, nuclear and streptococcal antigens in patients with rheumatic fever. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,DIV INFECT DIS,BOSTON,MA 02115. UNIV CAPE TOWN,RED CROSS WAR MEM CHILDRENS HOSP,DEPT PAEDIAT & CHILD HLTH,CAPE TOWN 7700,SOUTH AFRICA. RP EICHBAUM, QG (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115, USA. NR 16 TC 4 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD SEP PY 1995 VL 54 IS 9 BP 740 EP 743 DI 10.1136/ard.54.9.740 PG 4 WC Rheumatology SC Rheumatology GA RR784 UT WOS:A1995RR78400012 PM 7495346 ER PT J AU LOCKE, JL AF LOCKE, JL TI PSYCHOLINGUISTICS - GLEASON,JB, RATNER,NB SO APPLIED PSYCHOLINGUISTICS LA English DT Book Review RP LOCKE, JL (reprint author), MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0142-7164 J9 APPL PSYCHOLINGUIST JI Appl. Psycholinguist. PD SEP PY 1995 VL 16 IS 3 BP 347 EP 349 PG 3 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA TA542 UT WOS:A1995TA54200009 ER PT J AU MARTIN, A TOPE, WD GREVELINK, JM STARR, JC FEWKES, JL FLOTTE, TJ DEUTSCH, TF ANDERSON, RR AF MARTIN, A TOPE, WD GREVELINK, JM STARR, JC FEWKES, JL FLOTTE, TJ DEUTSCH, TF ANDERSON, RR TI LACK OF SELECTIVITY OF PROTOPORPHYRIN-IX FLUORESCENCE FOR BASAL-CELL CARCINOMA AFTER TOPICAL APPLICATION OF 5-AMINOLEVULINIC ACID - IMPLICATIONS FOR PHOTODYNAMIC TREATMENT SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE BASAL CELL CARCINOMA; PROTOPORPHYRIN IX; PHOTODYNAMIC THERAPY; AMINOLEVULINIC ACID ID ENDOGENOUS PROTOPORPHYRIN; SINGLET OXYGEN; THERAPY AB Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell carcinoma (BCC) show significant recurrence rates, Exogenous 5-amino-levulinic acid (ALA) is converted by intracellular enzymes to photoactive protoporphyrin IX (PpIX) in human tissues. PpIX generates cytotoxic singlet oxygen when irradiated with visible light in the 400-640 nm range. To evaluate variability and heterogeneity in PpIX production by tumors in such trials, and to assess the usefulness of PpIX for marking skin tumors, we measured PpIX fluorescence distribution in BCC after topical application of 20% ALA cream. ALA cream was applied under occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4 h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in vivo photography, ex vivo video fluorescence imaging, and fluorescence microscopy. External macroscopic PpIX fluorescence, as assessed by in vivo and ex vivo imaging, correlated with the clinical presence of BCC, Examination by a digital imaging fluorescence microscope revealed inter- and intratumor fluorescence variability and heterogeneity, PpIX fluorescence corresponding to full tomor thickness was found in six superficial and four nodular tumors, and partial-thickness fluorescence was observed in five nodular tumors, but no PpIX fluorescence was observed in some areas of superficial, nodular and infiltrating tumors. In a significant number of nodular and infiltrating BCCs, topical ALA appeared to provide little or no PpIX in deep tumor lobules. In addition, no selectivity for tumor tissue versus normal epidermis was seen. The grossly brighter external PpIX fluorescence over tumors may be due, therefore, to enhanced penetration through tumor-reactive stratum corneum and to the tumor thickness. The absence of reproducible fluorescence marking of nodular and infiltrating BCC suggests that topical ALA, at least under the present delivery protocols, may not be a reliable regimen for photodynamic treatment of these BCCs. C1 DERMATOL ASSOCIATES SAN DIEGO CO,ENCINITAS,CA 92024. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. NR 12 TC 118 Z9 121 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD SEP PY 1995 VL 287 IS 7 BP 665 EP 674 PG 10 WC Dermatology SC Dermatology GA RN779 UT WOS:A1995RN77900009 PM 8534131 ER PT J AU FARRER, LA CUPPLES, A VANDUIJN, CM CONNORLACKE, L KIELY, DK GROWDON, JH AF FARRER, LA CUPPLES, A VANDUIJN, CM CONNORLACKE, L KIELY, DK GROWDON, JH TI RATE OF PROGRESSION OF ALZHEIMERS-DISEASE IS ASSOCIATED WITH GENETIC RISK SO ARCHIVES OF NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E TYPE-4; EARLY-ONSET; DEMENTIA; LINKAGE; ALLELE; LOCUS; CHROMOSOME-14; SEGREGATION; PREDICTORS; SUBTYPES AB Objective: To determine whether differences in genetic origin affect the clinical course of Alzheimer's disease (AD). The limited number of cases of AD linked to a known genetic abnormality is a major obstacle in determining whether the disorder is expressed differently in patients with familial AD and those with sporadic AD. Design: Cross-sectional study. Setting: Memory Disorders Unit of the Alzheimer's Disease Research Center at Massachusetts General Hospital, Boston. Participants: A total of 186 patients who had a clinical diagnosis of probable AD, family history information available for all first-degree relatives, and three or more outpatient visits were identified from a consecutive case series. Main Outcome Measure: Rate of decline on the Blessed Dementia Scale and the Activities of Daily Living Scale. Results: We calculated the probability that an individual patient has a major genetic locus for AD (MGAD) using an algorithm that incorporates information from a genetic model and the individual's family. We measured cognitive and functional changes by the average annual rate of increase (slope) in scores for the Blessed Dementia Scale and Activities of Daily Living Scale, respectively. Multivariate analysis adjusted for age at onset, duration of illness at entry into the study, and education level indicated that scores on the Activities of Daily Living Scale worsened significantly faster in men with MGAD than in men with non-MGAD. No differences in Activities of Daily Living Scale slopes were observed among women with MGAD and non-MGAD. The slopes for Blessed Dementia Scale scores were similar in men and women regardless of the MGAD probability. Conclusions: Genetic factors may account for heterogeneity in rates of functional decline in AD. This study also illustrates the practical application of a probabilistic method that characterizes the genetic status of AD in an individual patient. C1 BOSTON UNIV,SCH PUBL HLTH,DEPT BIOSTAT & EPIDEMIOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. ERASMUS UNIV ROTTERDAM,DEPT EPIDEMIOL,ROTTERDAM,NETHERLANDS. RP FARRER, LA (reprint author), BOSTON UNIV,SCH MED,DEPT NEUROL,80 E CONCORD ST,BOSTON,MA 02118, USA. OI Farrer, Lindsay/0000-0001-5533-4225 FU NIA NIH HHS [P50-AG05134, R01-AG09029] NR 41 TC 24 Z9 25 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD SEP PY 1995 VL 52 IS 9 BP 918 EP 923 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA RT888 UT WOS:A1995RT88800014 PM 7661731 ER PT J AU GATES, JD HIRSCH, GM KARNOVSKY, MJ AF GATES, JD HIRSCH, GM KARNOVSKY, MJ TI SUPPRESSORS OF OXYGEN METABOLITES FAIL TO REDUCE VEIN GRAFT INTIMAL HYPERPLASIA SO ARCHIVES OF SURGERY LA English DT Article ID XANTHINE-OXIDASE; ENDOTHELIAL-CELLS; FREE-RADICALS; ALLOPURINOL; PLASMA; RAT; REOXYGENATION; INHIBITION; OXIPURINOL; OXYPURINOL AB Objective: To evaluate the role of reactive oxygen metabolites in the initiation of intimal hyperplasia of vein grafts inserted into the arterial circulation. Setting: University pathologic research laboratory. Animals: Sprague-Dawley rats. Intervention: Animals were randomized to receive either the xanthine oxidase inhibitor allopurinol, the iron chelating agent starch-conjugated deferoxamine, or the free-radical scavenger 21-aminosteroid U74389G. Control animals were included for each group. The epigastric vein was inserted into the right common femoral artery. Vein grafts were harvested 30 days postoperatively. The degree of intimal hyperplasia at the two anastomoses as well as at the midgraft was calculated. Main Outcome Measures: The vein grafts were divided into three sections designated proximal anastomosis, midgraft, and distal anastomosis. Intimal and medial areas were determined in an observer-blind fashion and expressed as intimal area-medial area ratios. Results: Pretreatment of the animals with any of these agents resulted in no significant reduction in the degree of intimal hyperplasia in any treated groups compared with the control animals 30 days postoperatively. Conclusions: Arterial reconstruction often involves interposition of vein segments into the arterial circulation. These veins are subject to ischemia and reperfusion, with the potential for generation of reactive oxygen metabolites and subsequent vein graft injury, resulting in intimal hyperplasia. We hypothesized that perioperative pharmacologic intervention either to scavenge or to reduce the production of reactive oxygen metabolites would attenuate the initial vein graft injury and thus limit the subsequent development of intimal hyperplasia. These data create doubt as to the influence of reactive oxygen metabolites in the initiation of intimal hyperplasia in the vein graft. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP GATES, JD (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 30 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD SEP PY 1995 VL 130 IS 9 BP 976 EP 980 PG 5 WC Surgery SC Surgery GA RU327 UT WOS:A1995RU32700020 PM 7661683 ER PT J AU FUHLBRIGGE, RC ALON, R SPRINGER, TA AF FUHLBRIGGE, RC ALON, R SPRINGER, TA TI REGULATION OF LYMPHOCYTE SELECTIN LIGAND EXPRESSION BY FUGOSYLTRANSFERASES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 14 EP 14 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400014 ER PT J AU KATZ, P WHALEN, G KEHRL, JH KYRIAKIS, JH AF KATZ, P WHALEN, G KEHRL, JH KYRIAKIS, JH TI ACTIVATION OF THE STRESS-ACTIVATED PROTEIN-KINASE (SAPK) PATHWAY BY A NOVEL GERMINAL CENTER B-CELL KINASE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. GEORGETOWN UNIV,WASHINGTON,DC 20007. NIAID,UR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 166 EP 166 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400166 ER PT J AU MERKEL, PA NILES, JL SKATES, J CONVERY, K POLISSON, RP AF MERKEL, PA NILES, JL SKATES, J CONVERY, K POLISSON, RP TI THE PREVALENCE OF ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES IN A VARIETY OF CONNECTIVE-TISSUE DISEASES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 337 EP 337 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400337 ER PT J AU FRASER, PA LEHMAN, TJ SUNDEL, R JACKSON, J ALEXANDERTHOMAS, N DECEULAER, K DING, W AUDEH, M AF FRASER, PA LEHMAN, TJ SUNDEL, R JACKSON, J ALEXANDERTHOMAS, N DECEULAER, K DING, W AUDEH, M TI THE TTHIII1 RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISM (RFLP) OF THE HUMAN FAS GENE IS ASSOCIATED WITH EARLY-ONSET LUPUS IN POPULATIONS OF AFRICAN ANCESTRY SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA. HOSP SPECIAL SURG,NEW YORK,NY 10021. CHILDRENS HOSP,PHILADELPHIA,PA 19104. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL,BOSTON,MA. HARLEM HOSP MED CTR,NEW YORK,NY 10037. UNIV W INDIES,KINGSTON,JAMAICA. CTR BLOOD RESEARCH INC,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 683 EP 683 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400682 ER PT J AU SIEPER, J WU, PH WUCHERPFENNIG, K BRAUN, J AF SIEPER, J WU, PH WUCHERPFENNIG, K BRAUN, J TI CD4+ T-CELL RESPONSE TO A HLA B27-DERIVED PEPTIDE IN ANKYLOSING-SPONDYLITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 FREE UNIV BERLIN,KLINIKUM BENJAMIN FRANKLIN,W-1000 BERLIN,GERMANY. DEUTSCH RHEUMAFORSCHUNGSZENTRUM,BERLIN,GERMANY. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 972 EP 972 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68400971 ER PT J AU CLEGG, DO REDA, DJ AF CLEGG, DO REDA, DJ TI COMPARISON OF SULFASALAZINE AND PLACEBO FOR THE TREATMENT OF AXIAL, OLIGOARTICULAR AND POLYARTICULAR MANIFESTATIONS OF THE SERONEGATIVE SPONDYLOARTHROPATHIES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 US DEPT VET AFFAIRS,COOPERAT STUDIES PROGRAM,HINES,IL 60141. US DEPT VET AFFAIRS,COOPERAT STUDIES PROGRAM,SALT LAKE CITY,UT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1176 EP 1176 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401175 ER PT J AU MERKEL, PA DOOLEY, MA DAWSON, DV PISETSKY, DS POLISSON, RP AF MERKEL, PA DOOLEY, MA DAWSON, DV PISETSKY, DS POLISSON, RP TI INTERLEUKIN-2 RECEPTOR LEVELS IN THE SERA OF RHEUMATOID-ARTHRITIS PATIENTS TREATED WITH SULFASALAZINE, PARENTERAL GOLD, OR PLACEBO SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DUKE UNIV,MED CTR,DURHAM,NC 27710. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1292 EP 1292 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401291 ER PT J AU LUSK, RH WIENKE, EC MILLIGAN, TW ALBUS, TE AF LUSK, RH WIENKE, EC MILLIGAN, TW ALBUS, TE TI TUBERCULOUS AND FOREIGN-BODY GRANULOMATOUS REACTIONS INVOLVING A TOTAL KNEE PROSTHESIS SO ARTHRITIS AND RHEUMATISM LA English DT Note ID TOTAL HIP-REPLACEMENT; BONE-RESORPTION; ARTHROPLASTY AB This case report describes loosening of a right knee prosthesis and represents the first report of the simultaneous occurrence of 2 granulomatous processes involving a prosthetic joint. Microscopic examination of the tissue revealed areas of foreign-body granulomas and areas of necrotizing granulomas and caseation, Acid-fast bacilli cultures were positive for Mycobacterium tuberculosis. The pathophysiology of implant loosening following an inflammatory reaction to components of prosthetic materials is discussed. Also discussed is the occurrence of infectious complications and rarity of tuberculous infections associated with prosthetic implants. C1 VET AFFAIRS MED CTR,ST LOUIS,MO. DEACONESS MED CTR,ST LOUIS,MO. RP LUSK, RH (reprint author), ST LOUIS UNIV,HLTH SCI CTR,SCH MED,DIV INFECT DIS,3635 VISTA AVE,ST LOUIS,MO 63110, USA. NR 12 TC 13 Z9 14 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 BP 1325 EP 1327 DI 10.1002/art.1780380921 PG 3 WC Rheumatology SC Rheumatology GA RW603 UT WOS:A1995RW60300020 PM 7575728 ER PT J AU GOLDRING, MB YAMIN, R SANDELL, LJ AF GOLDRING, MB YAMIN, R SANDELL, LJ TI OVERLAPPING DISTAL PROMOTER ELEMENTS RESPONSIVE TO INTERLEUKIN-1-BETA IN THE HUMAN TYPE-II COLLAGEN GENE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV WASHINGTON,SEATTLE,WA 98195. VET ADM MED CTR,SEATTLE,WA 98195. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1412 EP 1412 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401410 ER PT J AU NAKABAVASHI, T DANG, H KONG, L GAISER, A LETTERIO, J TALAL, N AF NAKABAVASHI, T DANG, H KONG, L GAISER, A LETTERIO, J TALAL, N TI UP-REGULATION OF CYTOKINE GENE AND ADHESION MOLECULE PROTEIN EXPRESSION IN THE SALIVARY-GLANDS OF TGF-BETA-1 NULL MICE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1496 EP 1496 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401494 ER PT J AU OGAWA, N DANQ, H KONG, L ANAYA, LM LIU, GT TALAL, N AF OGAWA, N DANQ, H KONG, L ANAYA, LM LIU, GT TALAL, N TI ANALYSIS OF APOPTOSIS-ASSOCIATED GENE-EXPRESSION IN LYMPHOCYTES FROM SJORGENS SYNDROME (SS) PATIENTS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1995 VL 38 IS 9 SU S BP 1497 EP 1497 PG 1 WC Rheumatology SC Rheumatology GA RX684 UT WOS:A1995RX68401495 ER PT J AU BOWNDS, MD ARSHAVSKY, VY AF BOWNDS, MD ARSHAVSKY, VY TI WHAT ARE THE MECHANISMS OF PHOTORECEPTOR ADAPTATION SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Article DE CALCIUM; CYCLIC GMP; CYCLIC GMP PHOSPHODIESTERASE; GUANYLATE CYCLASE; LIGHT ADAPTATION; PHOSPHORYLATION; PHOTORECEPTOR; RHODOPSIN; ROD OUTER SEGMENTS; TRANSDUCIN ID ROD OUTER SEGMENTS; CYCLIC-GMP PHOSPHODIESTERASE; CYTOSOLIC FREE CALCIUM; PROTEIN-KINASE-C; LIGHT-INDUCED-CHANGES; BOVINE RETINAL RODS; CGMP-BINDING-SITES; RHODOPSIN KINASE; VISUAL TRANSDUCTION; VERTEBRATE PHOTORECEPTORS AB This article evaluates each of the reactions known to be involved in visual transduction as a potential site for the regulation of light adaptation. Extensive evidence suggests that calcium acts as a feedback messenger at several different points and recent work suggests a role for cGMP in regulating the primary excitatory pathway. A conclusion is that adaptation is likely to be regulated by multiple and redundant mechanisms. The goal of future experimentation will be to determine the relative importance of each of these. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RP BOWNDS, MD (reprint author), UNIV WISCONSIN,MOLEC BIOL LAB,MADISON,WI 53706, USA. NR 182 TC 36 Z9 36 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1995 VL 18 IS 3 BP 415 EP 424 PG 10 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA TJ300 UT WOS:A1995TJ30000003 ER PT J AU PRENCE, EM AF PRENCE, EM TI EFFECTS OF CALCIUM ON PHOSPHATIDYLSERINE-STIMULATED AND SAPOSIN-C-STIMULATED GLUCOSYLCERAMIDE BETA-GLUCOSIDASE ACTIVITY SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; GAUCHERS-DISEASE; REPLACEMENT THERAPY; ACTIVATOR PROTEIN; GLUCOCEREBROSIDASE; DEFICIENCY; MEMBRANE; SPLEEN; SPHINGOLIPIDOSES; PURIFICATION AB Glucosylceramide beta-glucosidase is a membrane-bound lysosomal hydrolase that is activated by acidic lipids, the most effective of which is phosphatidylserine (PtdSer), and an activator protein, saposin C. This report documents effects of Ca2+ ions on PtdSer- and saposin C-enhanced beta-glucosidase activity. Ca2+ either increased or decreased enzyme activity, depending on (1) the concentration of phospholipid, and (2) the presence or absence of saposin C. At PtdSer concentrations between 7.6 and 76 mu M, in the absence of saposin C, Ca2+ caused an increase in beta-glucosidase activity up to 3 times that measured with PtdSer alone; this was due to both an increase in V-max and a decrease in K-m. In contrast, at PtdSer concentrations greater than 100 mu M, Ca2+ inhibited beta-glucosidase activity by 50%, due to a 2-fold increase in K-m. Ca2+ was inhibitory at all PtdSer concentrations tested when both PtdSer and saposin C were present in the assay. Ca2+ ions were also shown to cause changes in the aggregation states of PtdSer. These results suggest that changes in Ca2+ concentration may play a role in regulating beta-glucosidase activity in vivo, thereby modulating sphingolipid metabolism. The implications of these findings are discussed. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. RP PRENCE, EM (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOCHEM,200 TRAPELO RD,WALTHAM,MA 02254, USA. NR 27 TC 5 Z9 5 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1995 VL 310 BP 571 EP 575 PN 2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR743 UT WOS:A1995RR74300032 PM 7654196 ER PT J AU KIM, KM BOUCHER, H TSIATIS, AA AF KIM, KM BOUCHER, H TSIATIS, AA TI DESIGN AND ANALYSIS OF GROUP SEQUENTIAL LOGRANK TESTS IN MAXIMUM DURATION VERSUS INFORMATION TRIALS SO BIOMETRICS LA English DT Article DE CLINICAL TRIALS; FAILURE TIME DATA; INFORMATION TIME; TYPE I ERROR SPENDING FUNCTION ID CLINICAL-TRIALS; DISTRIBUTIONS; CALENDAR AB When monitoring a clinical trial with failure time data using the logrank test and the type I error spending function approach, the information time has to be estimated as a fraction of the maximum number of failures. In maximum duration trials, the denominator of this fraction is a random quantity and has to be estimated; besides, there are two candidates for the denominator, one under the null hypothesis of no treatment difference and the other under the specified alternative hypothesis. Either way, some adjustments are necessary in determining group sequential boundaries in order to maintain type I error at a desired significance level. As a consequence, the type I error spending function will be altered from the one chosen for the design, thus affecting the operating characteristics of the subsequent group sequential logrank tests. In maximum information trials, however, the maximum amount of information is fixed, and thus the estimate of the information time is always unbiased. The net effect is that computation of group sequential boundaries becomes straightforward, with a potential saving in study durations as compared to maximum duration trials. We will illustrate how adjustments are made in maximum duration trials to maintain type I error when the information times are estimated with the information horizons under the null and alternative hypotheses and present numerical explorations to compare robustness of two different estimates of the information times. We then propose a design procedure for maximum information trials and investigate the properties of maximum information trials for different group sequential boundaries. We also compare maximum information trials and maximum duration trials based on an example. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP KIM, KM (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 52733]; NIAID NIH HHS [AI 24643] NR 19 TC 10 Z9 10 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1995 VL 51 IS 3 BP 988 EP 1000 DI 10.2307/2532999 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA RW742 UT WOS:A1995RW74200018 PM 7548714 ER PT J AU PLATT, OS FALCONE, JF AF PLATT, OS FALCONE, JF TI MEMBRANE-PROTEIN INTERACTIONS IN SICKLE RED-BLOOD-CELLS - EVIDENCE OF ABNORMAL PROTEIN-3 FUNCTION SO BLOOD LA English DT Article ID ERYTHROCYTE ANION-EXCHANGER; ANKYRIN-BINDING SITE; CYTOPLASMIC DOMAIN; HEMOGLOBIN BINDING; HEINZ BODIES; BETA-THALASSEMIA; BAND-3; SPECTRIN; ASSOCIATION; LOCALIZATION AB The pattern of membrane abnormalities in sickle rad blood cells suggests that sickle hemoglobin damages membrane proteins. We have previously shown a functional defect in sickle ankyrin, poor spectrin-binding ability. Here we examine the other major binding interactions of sickle membrane proteins including spectrin self-association, binding of ankyrin and protein 4.1 to protein 3, and the formation of the spectrin-actin-protein 4.1 complex. We found that sickle spectrin was normal in self-association and ability to participate in the spectrin-actin-protein 4.1 complex. Sickle protein 4.1 bound normally to protein 3 and formed normal complexes with actin and spectrin, even when sickle spectrin was used. The only major abnormality we found was a reduced ability of sickle protein 3 to bind ankyrin. This functional defect could not be explained experimentally on the basis of cysteine modification or enhanced tyrosine phosphorylatian. We conclude that damage of sickle membrane proteins is not a diffuse scattershot process, but is largely confined to regions near membrane associated hemoglobin, the spectrin-binding domain of ankyrin and the ankyrin-binding domain of protein 3. The mechanism and consequences of this damage continues to be investigated. (C) 1995 by The American Society of Hematology. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL & ONCOL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. RP PLATT, OS (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL15151] NR 59 TC 12 Z9 12 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 1995 VL 86 IS 5 BP 1992 EP 1998 PG 7 WC Hematology SC Hematology GA RT386 UT WOS:A1995RT38600042 PM 7655026 ER PT J AU CAPLAN, D AF CAPLAN, D TI ISSUES ARISING IN CONTEMPORARY-STUDIES OF DISORDERS OF SYNTACTIC PROCESSING IN SENTENCE COMPREHENSION IN AGRAMMATIC PATIENTS SO BRAIN AND LANGUAGE LA English DT Article ID GRAMMATICAL MORPHEMES; LANGUAGE DEFICITS; LEXICAL DECISION; WERNICKE APHASIA; CLOSED-CLASS; PREPOSITIONS; BROCA; DISSOCIATION; AVAILABILITY; SENSITIVITY AB This paper reviews recent studies of sentence comprehension in agrammatic patients. The conclusion is reached that more detailed study of individual patients is necessary to support hypotheses that have been presented concerning the deficit in these patients and that the rationale for studying comprehension in this group of patients is not well developed. A set of suggested criteria is presented for patient analysis in this field. (C) 1995 Academic Press, Inc. RP CAPLAN, D (reprint author), MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,VINCENT BURNHAM 827,FRUIT ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00942] NR 37 TC 22 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD SEP PY 1995 VL 50 IS 3 BP 325 EP 338 DI 10.1006/brln.1995.1051 PG 14 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA RL836 UT WOS:A1995RL83600004 PM 7583193 ER PT J AU LEE, WS LIMMROTH, V AYATA, C CUTRER, FM WAEBER, C YU, XJ MOSKOWITZ, MA AF LEE, WS LIMMROTH, V AYATA, C CUTRER, FM WAEBER, C YU, XJ MOSKOWITZ, MA TI PERIPHERAL GABA(A) RECEPTOR-MEDIATED EFFECTS OF SODIUM VALPROATE ON DURAL PLASMA-PROTEIN EXTRAVASATION TO SUBSTANCE-P AND TRIGEMINAL STIMULATION SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE DURA MATER; GABA RECEPTORS; MIGRAINE; MUSCIMOL; NEUROGENIC INFLAMMATION; SODIUM VALPROATE ID RAT SPINAL-CORD; BLOOD-VESSELS; SENSORY NEURONS; ERGOT ALKALOIDS; MATER; SUMATRIPTAN; HEADACHE; MIGRAINE; NERVE; IMMUNOREACTIVITY AB 1 The GABA transaminase inhibitor and activator of glutamic acid decarboxylase, valproic acid is being used for the treatment of migraine. Its mechanism of action is unknown. We tested the effects of sodium valproate and GABA(A)-agonist muscimol on dural plasma protein ([I-125]-bovine serum albumin) extravasation evoked by either unilateral trigeminal ganglion stimulation (0.6 mA, 5 ms, 5 Hz, 5 min) or substance P (SP) administration (1 nmol kg(-1),i.v.) in anaesthetized Sprague-Dawley rats. 2 Intraperitoneal (i.p.) injection of sodium valproate or muscimol, but not baclofen (less than or equal to 10 mg kg(-1), i.p.) dose-dependently reduced dural plasma protein extravasation caused either by electrical trigeminal stimulation (ED(50): 6.6 +/- 1.4 mg kg(-1), i.p., and 58 +/- 28 mu g kg(-1), i.p. for valproate or muscimol, respectively) or by intravenous substance P administration (ED(50): 3.2 +/- 1.4 mg kg(-1), i.p. and 385 +/- 190 mu g kg(-1), i.p. for valproate or muscimol, respectively). 3 Valproate (6.6 mg kg(-1), i.p.) or muscimol (58 mu g kg(-1), i.p.) had no effect on mean arterial blood pressure or heart rate when measured for 30 min after i.p. administration. 4 The GABA(A)-antagonist bicuculline (0.01 mg kg(-1), i.p.) completely reversed the effect of valproate and muscimol on plasma extravasation following electrical stimulation or substance P administration, whereas the GABA(B)-receptor antagonist, phaclofen (0.01-1 mg kg(-1), i.p.) did not. Bicuculline or phaclofen, given alone, did not alter the plasma extravasation response after either electrical stimulation or SP administration. 5 Valproate decreased plasma extravasation following substance P administration in adult animals, neonatally treated with capsaicin by a bicuculline-reversible mechanism. This suggests that GABA(A)-receptors are not found primarily on those afferent neurones or fibres which are sensitive to capsaicin treatment in neonatal rats. 6 We conclude that sodium valproate blocks plasma extravasation in the meninges through GABA(A)-mediated postjunctional receptors probably within the meninges. The dosages required are comparable to those used clinically. Agonists and modulators at the GABA(A) receptor may become useful for the development of selective therapeutic agents for migraine and cluster headache. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [NS21558] NR 47 TC 68 Z9 71 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HANTS, ENGLAND RG21 2XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 1995 VL 116 IS 1 BP 1661 EP 1667 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RR197 UT WOS:A1995RR19700019 PM 8564234 ER PT J AU FOSSA, S JONES, M JOHNSON, P JOFFE, J HOLDENER, E ELSON, P RITCHIE, A SELBY, P AF FOSSA, S JONES, M JOHNSON, P JOFFE, J HOLDENER, E ELSON, P RITCHIE, A SELBY, P TI INTERFERON-ALPHA AND SURVIVAL IN RENAL-CELL CANCER SO BRITISH JOURNAL OF UROLOGY LA English DT Article DE RENAL CELL CANCER; INTERFERON-ALPHA; CHEMOTHERAPY; PROGNOSTIC FACTORS ID SPONTANEOUS REGRESSION; CARCINOMA AB Objective To establish whether the use of interferon-alpha might result in improved survival, using two large series of patients with advanced renal cell cancer treated during studies of chemotherapy and biological therapy, respectively. Patients and methods Patients treated either in the Eastern Cooperative Oncology Group (ECOG) chemotherapy protocols (327 patients) or in protocols employing interferon as part of a European randomized study or phase II studies at the Norwegian Radium Hospital (231 patients) were retrospectively analysed. Groups for comparison were matched by exclusion of those with an ECOG performance status >2, no prior nephrectomy, brain metastases or prior chemotherapy. Univariate analysis of prognostic factors for survival was performed by the log rank method and multivariate analysis by Cox regression. Results Univariate analysis of the whole population showed that performance status, time from diagnosisto treatment, sites of metastases and the use of interferon carried the greatest prognostic significance. In multivariate analysis, the use of interferon remained a significant predictor of survival (P<0.001). Subgroup analysis suggested that the impact of interferon treatment was greatest in those patients with two of the following characteristics; good performance status, an interval of >2 years from diagnosis to treatment and no more than one site of metastasis. Conclusion Although a prospective randomized trial is needed to establish definite benefit from the use of interferon in advanced renal cell cancer, this analysis supports the rationale for performing such a trial, particularly in patients with relatively good prognostic features. Patients should be entered into the Medical Research Council study comparing interferon with medroxyprogesterone acetate. C1 ST JAMES UNIV HOSP,IMPERIAL CANC RES FUND,CANC MED RES UNIT,LEEDS LS9 7TF,W YORKSHIRE,ENGLAND. NORWEGIAN RADIUM HOSP,DEPT MED ONCOL & RADIOTHERAPY,N-0310 OSLO,NORWAY. DANA FARBER CANC INST,BOSTON,MA 02115. F HOFFMANN LA ROCHE & CO LTD,CH-4002 BASEL,SWITZERLAND. GLOUCESTERSHIRE ROYAL HOSP,DEPT UROL,GLOUCESTER GL1 3NN,ENGLAND. NR 18 TC 42 Z9 42 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1331 J9 BRIT J UROL JI Br. J. Urol. PD SEP PY 1995 VL 76 IS 3 BP 286 EP 290 DI 10.1111/j.1464-410X.1995.tb07702.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA RT180 UT WOS:A1995RT18000002 PM 7551834 ER PT J AU FLEMING, RA CAPIZZI, RL ROSNER, GL OLIVER, LK SMITH, SJ SCHIFFER, CA SILVER, RT PETERSON, BA WEISS, RB OMURA, GA MAYER, RJ VANECHO, DA BLOOMFIELD, CD SCHILSKY, RL AF FLEMING, RA CAPIZZI, RL ROSNER, GL OLIVER, LK SMITH, SJ SCHIFFER, CA SILVER, RT PETERSON, BA WEISS, RB OMURA, GA MAYER, RJ VANECHO, DA BLOOMFIELD, CD SCHILSKY, RL TI CLINICAL-PHARMACOLOGY OF CYTARABINE IN PATIENTS WITH ACUTE MYELOID-LEUKEMIA - A CANCER AND LEUKEMIA GROUP-B STUDY SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE CYTARABINE; LEUKEMIA ID HIGH-DOSE 1-BETA-D-ARABINOFURANOSYLCYTOSINE; CYTOSINE-ARABINOSIDE TRANSPORT; ARA-C; CELLS; METABOLISM; PHARMACOKINETICS; PHOSPHORYLATION; DEOXYCYTIDINE; ACCUMULATION; TOXICITY AB The pharmacokinetics of cytarabine (ara-C) were determined in 265 patients with acute myeloid leukemia (AML) receiving ara-C (200 mg/m(2) per day for 7 days as a continuous infusion) and daunorubicin during induction therapy. The mean (standard deviation) ara-C concentration at steady-state (Css) and systemic clearance (Cl) were 0.30 (0.13) mu M and 134(71) 1/h per m(2) respectively. Males had a significantly faster ara-C Cl (139 vs 131 1/h per m(2), P = 0.025) than females. Significant correlations were noted between ara-C Cl and the pretreatment, peripheral white blood cell count (P = 0.005) and pretreatment blast count (P = 0.020). No significant differences in ara-C Css or CI were noted in patients achieving complete remission compared with those failing therapy (P = 0.315, P = 0.344, respectively). No significant correlations were observed between ara-C pharmacokinetic parameters and several indices of patient toxicity. Our findings indicate that variability in ara-C disposition in plasma at this dosage level does not correlate with remission status or toxicity in patients with AML receiving initial induction therapy with ara-C and daunorubicin. C1 DUKE UNIV,MED CTR,DURHAM,NC. UPJOHN CO,KALAMAZOO,MI 49001. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. NEW YORK HOSP,NEW YORK,NY 10021. UNIV MINNESOTA,SCH MED,MINNEAPOLIS,MN 55455. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. UNIV ALABAMA,BIRMINGHAM,AL. DANA FARBER CANC INST,BOSTON,MA 02115. ROSWELL PK CANC INST,BUFFALO,NY 14263. UNIV CHICAGO,CANC RES CTR,CHICAGO,IL 60637. RP FLEMING, RA (reprint author), WAKE FOREST UNIV,CTR COMPREHENS CANC,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. FU NCI NIH HHS [CA-03927, CA-37027, CA-59518] NR 30 TC 13 Z9 14 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1995 VL 36 IS 5 BP 425 EP 430 DI 10.1007/BF00686192 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA RN819 UT WOS:A1995RN81900010 PM 7634384 ER PT J AU BROOKS, SE KORBUT, TT DUPUIS, NP HOLDEN, SA TEICHER, BA AF BROOKS, SE KORBUT, TT DUPUIS, NP HOLDEN, SA TEICHER, BA TI CYTOTOXICITY OF ANTITUMOR PLATINUM COMPLEXES WITH L-BUTHIONINE-(R,S)-SULFOXIMINE AND/OR ETANIDAZOLE IN HUMAN CARCINOMA CELL-LINES SENSITIVE AND RESISTANT TO CISPLATIN SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE BUTHIONINE SULFOXIMINE; ETANIDAZOLE; ANTITUMOR PLATINUM COMPLEXES; TETRAPLATIN ID MEDIATED GLUTATHIONE DEPLETION; MELPHALAN CYTO-TOXICITY; L-PHENYLALANINE MUSTARD; DNA CROSS-LINKING; BUTHIONINE SULFOXIMINE; OVARIAN-CARCINOMA; TUMOR-CELLS; ALKYLATING-AGENTS; DRUG-RESISTANCE; CANCER AB Human 2008 ovarian carcinoma cells and the C13 CDDP-resistant subline and human MCF-7 breast carcinoma cells and the MCF-7/CDDP CDDP-resistant subline were exposed to L-buthionine(S, R)-sulfoximine (50 mu M) for 48 h prior to and during exposure for 1 h to the antitumor platinum complexes, cis-diamminedichloroplatinum(II), carboplatin or D,L-tetraplatin and/or to etanidazole (1 mM) for 2 h prior to and during exposure for 1 to the antitumor platinum complexes. These modulators alone did not significantly alter the cytotoxicity of CDDP toward either parental line. A twofold enhancement in cytotoxicity was observed with carboplatin in the 2008 cells and with D,L-tetraplatin in both parental lines with the single modulators. The modulator combination (buthionine sulfoximine/etanidazole) was very effective along with D,L-tetraplatin in both the MCF-7 parent and MCF-7/CDDP cell lines where at the higher platinum complex concentrations there was 1.5 to 3 logs increased killing of cells by the drug plus the modulators compared with the drug alone. Similarly, when C13 cells were exposed to CDDP (100 mu M) or D,L-tetraplatin (100 mu M) along with buthionine sulfoximine and etanidazole there was a 2-log increase in cell killing compared with exposure to the platinum complex alone. Treatment of each of the four cell lines with buthionine sulfoximine decreased both the non-protein and total sulfhydryl content of the cells. Treatment with the combination of modulators did not produce a further decrease in cellular sulfhydryl content compared with buthionine sulfoximine alone. The total sulfhydryl content in MCF-7 cells and 2008 cells exposed to buthionine sulfoximine and etanidazole was 58% and 31% of normal and the total sulfhydryl content of MCF-7/CDDP cells and C13 cells treated the same way was 54% and 23% of normal, respectively. DNA alkaline elution was used to assess the impact of exposure to the modulators, buthionine sulfoximine and etanidazole, alone and in combination on the cross linking of DNA by the antitumor platinum complexes in the MCF-7 and MCF-7/CDDP cell lines. Overall, the increases in DNA cross linking factors were greater in the MCF-7 cells than in the MCF-7/CDDP cells. These results indicate a possible clinical potential for this modulator combination. C1 DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. UNIV MASSACHUSETTS,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,WORCESTER,MA 01655. FU NCI NIH HHS [P01-CA 38493] NR 84 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD SEP PY 1995 VL 36 IS 5 BP 431 EP 438 DI 10.1007/BF00686193 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA RN819 UT WOS:A1995RN81900011 PM 7634385 ER PT J AU LI, FP LONDON, WT AF LI, FP LONDON, WT TI THE 4TH AMERICAN-CANCER-SOCIETY AWARD FOR RESEARCH EXCELLENCE IN CANCER-EPIDEMIOLOGY AND PREVENTION - INTRODUCTION SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID LI-FRAUMENI SYNDROME; BREAST-CANCER; COLON-CANCER; MOLECULAR EPIDEMIOLOGY; P53 MUTATIONS; GENETICS; FAMILIES; THERAPY; TUMORS; GENES C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP LI, FP (reprint author), DANA FARBER CANC INST,MAYAR 3A31,44 BINNEY ST,BOSTON,MA 02115, USA. NR 58 TC 25 Z9 25 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1995 VL 4 IS 6 BP 579 EP 582 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RU350 UT WOS:A1995RU35000001 PM 8547822 ER PT J AU HUNCHAREK, M MUSCAT, J AF HUNCHAREK, M MUSCAT, J TI GENETIC-CHARACTERISTICS OF PROSTATE-CANCER SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID GROWTH-FACTOR RECEPTOR; MYC PROTOONCOGENE; FLOW-CYTOMETRY; RAS ONCOGENE; HUMAN-BREAST; DNA CONTENT; C-MYC; CARCINOMA; EXPRESSION; P53 AB Prostate cancer is the most commonly diagnosed malignancy in United States males, Unfortunately, numerous controversies surround clinical management for early stage disease and the utility of population screening. Much of this controversy stems from the lack of knowledge about the biology of prostate cancer, including the lack of clearly defined risk factors, absence of markers indicative of aggressive clinical behavior, as well as a lack of a clear understanding of its underlying genetic features. This paper reviews currently available evidence regarding the genetic characteristics of adenocarcinoma of the prostate, including the impact of family history on disease risk, the nature of structural genetic aberrations, and the possible role of oncogenes and tumor suppressor genes in its pathogenesis. A clearer understanding of these issues will hopefully lead to more effective and rational treatment policies in addition to the development of effective disease prevention strategies. C1 AMER HLTH FDN,DIV EPIDEMIOL,NEW YORK,NY 10017. RP HUNCHAREK, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,COX-B,BOSTON,MA 02114, USA. NR 65 TC 18 Z9 18 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1995 VL 4 IS 6 BP 681 EP 687 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA RU350 UT WOS:A1995RU35000016 PM 8547836 ER PT J AU PLANCHON, SM WUERZBERGER, S FRYDMAN, B WITIAK, DT HUTSON, P CHURCH, DR WILDING, G BOOTHMAN, DA AF PLANCHON, SM WUERZBERGER, S FRYDMAN, B WITIAK, DT HUTSON, P CHURCH, DR WILDING, G BOOTHMAN, DA TI BETA-LAPACHONE-MEDIATED APOPTOSIS IN HUMAN PROMYELOCYTIC LEUKEMIA (HL-60) AND HUMAN PROSTATE-CANCER CELLS - A P53-INDEPENDENT RESPONSE SO CANCER RESEARCH LA English DT Note ID DNA TOPOISOMERASE-I; CAMPTOTHECIN; CARCINOMA; REPAIR; INHIBITOR; CULTURES; BREAKS AB beta-Lapachone and certain of its derivatives directly bind and inhibit topoisomerase I (Topo I) DNA unwinding activity and form DNA-Topo I complexes, which are not resolvable by SDS-K+ assays. We show that beta-lapachone can induce apoptosis in certain cells, such as in human promyelocytic leukemia (HL-60) and human prostate cancer (DU-145, PC-3, acid LNCaP) cells, as also described by Li et al. (Cancer Res., 55: 0000-0000, 1995). Characteristic 180-200-bp oligonucleosome DNA laddering and fragmented DNA-containing apoptotic cells via flow cytometry and morphological examinations were observed in 4 h in HL-60 cells after a 4-h, greater than or equal to 0.5 mu M beta-lapachone exposure. HL-60 cells treated with camptothecin or topotecan resulted in greater apoptotic DNA laddering and apoptotic cell populations than comparable equitoxic concentrations of beta-lapachone, although beta-lapachone was a more effective Topo I inhibitor. beta-Lapachone treatment (4 h, 1-5 mu M) resulted in a block at G(0)/G(1), with decreases in S and G(2)/M phases and increases in apoptotic cell populations over time in HL-60 and three separate human prostate cancer (DU-145, PC-3, and LNCaP) cells. Similar treatments with topotecan or camptothecin (4 h, 1-5 mu M) resulted in blockage of cells in S and apoptosis. Thus, beta-lapachone causes a block in G(0)/G(1) of the cell cycle and induces apoptosis in cells before, or at early times during, DNA synthesis. These events are p53 independent, since PC-3 and HL-60 cells are mil cells, LNCaP are wild-type, and DU-145 contain mutant p53, yet all undergo apoptosis after beta-lapachone treatment. Interestingly, beta-lapachone treatment of p53 wild type-containing prostate cancer cells (i.e., LNCaP) did not result in the induction of nuclear levels of p53 protein, as did camptothecin-treated cells. Like other Topo I inhibitors, beta-lapachone may induce apoptosis by locking Topo I onto DNA, blocking replication fork movement, and inducing apoptosis in a p53-independent fashion. beta-Lapachone and its derivatives, as well as other Topo I inhibitors, have potential clinical utility alone against human leukemia and prostate cancers. C1 UNIV WISCONSIN,SCH MED,DEPT HUMAN ONCOL,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. UNIV WISCONSIN,SCH MED,DIV MED CHEM,MADISON,WI 53792. UNIV WISCONSIN,SCH PHARM,DEPT HUMAN ONCOL,MADISON,WI 53792. UNIV WISCONSIN,SCH PHARM,DEPT MED,MADISON,WI 53792. UNIV WISCONSIN,SCH PHARM,DIV MED CHEM,MADISON,WI 53792. RI Planchon, Sarah/A-5731-2009 FU NCI NIH HHS [R01 CA092250] NR 22 TC 182 Z9 186 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3706 EP 3711 PG 6 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900006 PM 7641180 ER PT J AU LI, CJ WANG, CL PARDEE, AB AF LI, CJ WANG, CL PARDEE, AB TI INDUCTION OF APOPTOSIS BY BETA-LAPACHONE IN HUMAN PROSTATE-CANCER CELLS SO CANCER RESEARCH LA English DT Note ID TOPOISOMERASE-I; DEATH; POLYMERASE; INHIBITOR; LETHALITY AB beta-Lapachone, a plant product, has been shown to be a novel inhibitor of DNA topoisomerase I, with a mode of action different from camptothecin and a chemical structure distinct from those of current anti-cancer drugs, Wie observed that beta-lapachone, at concentrations of less than 8 mu M, induces cell death with characteristics of apoptosis in human prostate cancer cell lines. This effect of beta-lapachone was also observed in a human promyelocytic leukemia cell line (HL-60). beta-Lapachone-induced apoptosis is independent of p53 expression, and ectopic overexpression of bcl-2 did not confer significant resistance to beta-lapachone, Among other human carcinoma and adenoma cell lines tested, human breast and ovary carcinoma showed sensitivity to the cytotoxic effect of beta-lapachone without manifesting signs of apoptosis, These results suggest that beta-lapachone is a potential compound to be added to cancer chemotherapy, particularly for prostate cancer. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP LI, CJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-35511] NR 21 TC 151 Z9 156 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3712 EP 3715 PG 4 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900007 PM 7641181 ER PT J AU YUAN, F DELLIAN, M FUKUMURA, D LEUNIG, M BERK, DA TORCHILIN, VP JAIN, RK AF YUAN, F DELLIAN, M FUKUMURA, D LEUNIG, M BERK, DA TORCHILIN, VP JAIN, RK TI VASCULAR-PERMEABILITY IN A HUMAN TUMOR XENOGRAFT - MOLECULAR-SIZE DEPENDENCE AND CUTOFF SIZE SO CANCER RESEARCH LA English DT Note ID HUMAN ADENOCARCINOMA LS174T; BLOOD-BRAIN-BARRIER; MICROVASCULAR PERMEABILITY; CAPILLARY-PERMEABILITY; INTERSTITIAL PRESSURE; SOLID TUMORS; SCID MICE; MACROMOLECULES; FLOW; EXTRAVASATION AB Molecular size is one of the key determinants of transvascular transport of therapeutic agents in tumors. However, there are no data in the literature on the molecular size dependence of microvascular permeability in tumors. Therefore, we measured microvascular permeability to various macromolecules in the human colon adenocarcinoma LS174T transplanted in dorsal skin chambers in severe combined immunodeficient mice. These molecules were fluorescently labeled and injected i.v. into mice. The microvascular permeability was calculated from the fluorescence intensity measured by the intravital fluorescence microscopy technique. The value of permeability varied approximately 2-fold in the range of molecular weight from 25,000 to 160,000. These data indicate that tumor vessels are less permselective than normal vessels, presumably due to large pores in the vessel wall. The transport of macromolecules appears to be limited by diffusion through these pores. The cutoff size of the pores was estimated by observations of transvascular transport of sterically stabilized liposomes of 100-600 nm in diameter. We found that tumor vessels in our model were permeable to liposomes of up to 400 nm in diameter, suggesting that the cutoff size of the pores is between 400 and 600 mm in diameter. C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP YUAN, F (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. RI Yuan, Fan/A-1287-2011; Berk, David/A-4863-2012; Leunig, Michael/E-7951-2017 OI Berk, David/0000-0002-3855-6886; Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [CA59255, R35-CA56591] NR 32 TC 1075 Z9 1114 U1 12 U2 101 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3752 EP 3756 PG 5 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900016 PM 7641188 ER PT J AU HUANG, M WANG, JY LEE, P SHARMA, S MAO, JT MEISSNER, H UYEMURA, K MODLIN, R WOLLMAN, J DUBINETT, SM AF HUANG, M WANG, JY LEE, P SHARMA, S MAO, JT MEISSNER, H UYEMURA, K MODLIN, R WOLLMAN, J DUBINETT, SM TI HUMAN NON-SMALL-CELL LUNG-CANCER CELLS EXPRESS A TYPE-2 CYTOKINE PATTERN SO CANCER RESEARCH LA English DT Article ID HUMAN-MONOCYTES; IMMUNE-RESPONSE; GENE-EXPRESSION; MESSENGER-RNA; TUMOR-GROWTH; IFN-GAMMA; IN-VITRO; LYMPHOKINE; IL-4; INTERLEUKIN-10 AB In addition to infiltrating inflammatory cells, tumors also produce cytokines and growth factors that may alter tumor growth, tumor immunogenicity, and the host immune response. To characterize the expression profile of human non-small cell lung cancer (NSCLC)-derived cytokines, the mRNA expression of type 1 and type 2 cytokines in five human NSCLC lines was analyzed by reverse transcriptase-PCR. Expression of interleukin 5 (IL-5) and IL-10 was demonstrated in all tumor lines evaluated, whereas IL-4 was present in three of five lines and IL-13 was present in two of five lines. In contrast, none of the tumor lines expressed IL-2 and IFN-gamma. Type 2 cytokine protein production by NSCLC lines was confirmed by immunoprecipitation and cytokine specific ELISA. Tumor-derived IL-10 secretion was significantly augmented by exogenous recombinant cytokines including IL-4 and tumor necrosis factor-alpha. To evaluate whether fresh NSCLC nodules also express a type 2 cytokine pattern, the content of type 1 and type 2 cytokines in tissue homogenates from 13 fresh NSCLC nodules and normal lung surgical specimens was assessed. Human NSCLC nodules contain significantly more type 2 cytokines than does normal lung tissue when corrected for total protein concentration. To identify the cellular source of type 2 cytokine production in tumor nodules, immunohistology was performed on sections from 5 lung squamous cell carcinomas and 5 adenocarcinomas. All of the specimens revealed positive staining for type 2 cytokines within tumor cells. In summary, we report that human NSCLC cells produce type 2 cytokines both in situ and in vitro, which may play an active immunoregulatory role in the lung cancer microenvironment C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,SCH MED,DEPT MED,DIV PULM & CRIT CARE MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,JOHNSON COMPREHENS CANC CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DIV DERMATOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90073. VET ADM MED CTR,LOS ANGELES,CA 90073. RI Modlin, Robert/M-7941-2014 OI Modlin, Robert/0000-0003-4720-031X FU NCI NIH HHS [CA09120]; NHLBI NIH HHS [HL07014] NR 66 TC 224 Z9 250 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3847 EP 3853 PG 7 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900032 PM 7641203 ER PT J AU ZHU, JG FROSCH, MP BUSQUE, L BEGGS, AH DASHNER, K GILLILAND, DG BLACK, PM AF ZHU, JG FROSCH, MP BUSQUE, L BEGGS, AH DASHNER, K GILLILAND, DG BLACK, PM TI ANALYSIS OF MENINGIOMAS BY METHYLATION-BASED AND TRANSCRIPTION-BASED CLONALITY ASSAYS SO CANCER RESEARCH LA English DT Article ID X-CHROMOSOME INACTIVATION; POLYMERASE CHAIN-REACTION; HUMAN-TUMORS; PARATHYROID ADENOMAS; DNA METHYLATION; PROBE M27-BETA; BREAST-CANCER; BRAIN-TUMORS; PATTERNS; GENE AB The clonal derivation of tumors can be determined by X chromosome inactivation analysis based on differential expression of genes or differential methylation of cytosine residues in CpG islands near polymorphic loci, In this report, we compared a transcription-based RNA analysis with a methylation-based DNA assay to determine clonality of meningiomas. Both clonality assays use PCR-based analysis at the human androgen-receptor gene (HUMARA) on the X chromosome. Among 23 meningiomas from female patients, 19 were informative heterozygotes at this locus (83%), The patterns of X chromosome inactivation in four patients were extremely skewed towards one allele in blood (unequal Lyonization), which precluded clonality determination in the tumor samples, Concordant clonality results with methylation- and transcription-based clonality assays were demonstrated in 9 of 13 informative tumors expressing the androgen receptor, Seven meningiomas were monoclonal, but surprisingly, two pathologically documented cases of meningiomas were polyclonal, There was disparity in 4 of 13 tumor specimens that were polyclonal by the methylation-based assay but monoclonal by the transcription assay, Clonality examination of these tumors by the methylation-based phosphoglycerate kinase assay provided identical results to the methylation-based analysis at the HUMARA locus, In addition, loss of heterozygosity (LOH) studies of chromosome 22, which is frequently deleted in meningiomas, showed that four of four informative samples of the six polyclonal tumors had partial LOH in tumor tissues, However, complete LOH was observed in primary cultured cells, which were also monoclonal by the methylation assay. Taken together, these data suggest that the disparity of the two assays in these four cases may be due to differences in the level of expression of the androgen receptor gene in tumors, Therefore, we conclude that: (a) clonal derivation of meningiomas determined by both transcription- and methylation-based clonality assays are in full agreement in many (9 of 13) but not all cases (4 of 13); and (b) most meningiomas (9 of 15) are monoclonal in origin, whereas some meningioma samples (6 of 15) are polyclonal or may contain heterogeneous components. C1 BRIGHAM & WOMENS HOSP,NEUROSURG LABS,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,CTR BRAIN TUMOR,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT SURG,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP,DIV GENET,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 52 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1995 VL 55 IS 17 BP 3865 EP 3872 PG 8 WC Oncology SC Oncology GA RR739 UT WOS:A1995RR73900035 PM 7641206 ER PT J AU GARCIA, AR DEACON, TW DINSMORE, J ISACSON, O AF GARCIA, AR DEACON, TW DINSMORE, J ISACSON, O TI EXTENSIVE AXONAL AND GLIAL FIBER GROWTH FROM FETAL PORCINE CORTICAL XENOGRAFTS IN THE ADULT-RAT CORTEX SO CELL TRANSPLANTATION LA English DT Article DE AXON GROWTH; PARALYSIS; CEREBRAL CORTEX; DEVELOPMENT; FETAL GRAFTS; NEUROTROPISM ID CENTRAL-NERVOUS-SYSTEM; MYELIN-ASSOCIATED INHIBITORS; CNS WHITE MATTER; CEREBRAL-CORTEX; NEURITE GROWTH; NEOSTRIATAL TRANSPLANTS; MESENCEPHALIC NEURONS; MINIMAL CONNECTIVITY; STRIATAL NEURONS; BRAIN INJURY AB Axonal growth from cortically placed fetal neural transplants to subcortical targets in adult hosts has been difficult to demonstrate and is assumed to be minimal; however, experiments using xenogeneic neural grafts of either human or porcine fetal tissues into the adult rat striatum, mesencephalon, and spinal cord have demonstrated the capability for long-distance axonal growth. This study reports similar results for porcine cortical xenografts placed in the adult rat cerebral cortex and compares these findings with results from cortical allografts. Adult rats that previously received unilateral cortical lesions by an oblique intracortical stereotaxic injection of quinolinic acid, were implanted with suspensions of either E14 rat or E38 xenogeneic porcine fetal cortical cells. Xenografted rats were immunosuppressed by cyclosporin A. The corpus callosum was intact in all cases and grafts were confined to the overlying cortex. After a 31-34 wk posttransplant survival period, acetylcholinesterase (AChE) staining and tyrosine hydroxylase (TH) immunocytochemistry revealed that both allo- and xenografts received host afferents. Retrograde tracer injections into the ipsilateral striatum and cerebral peduncle in allografted animals failed to show any axonal growth to either subcortical target. Using a porcine-specific axonal marker in xenografted animals, we found graft axons in white matter tracts (corpus callosum, internal capsule, cingulum bundle, and medial forebrain bundle) and within the caudate-putamen and both the ipsilateral and contralateral cerebral cortex. Graft axons were not found in the thalamus, midbrain, or spinal cord. In addition, using an antibody to porcine glial fibers, we observed more extensive graft glial fiber growth into the same host fiber tracts, as far caudally as the cerebral peduncle, but not into gray matter targets outside the cortex. These results demonstrate that porcine cortical xenograft axons and glia can extend from lesioned cerebral cortex to cortical and subcortical targets in the adult rat brain. These findings are relevant for prospects of repairing cortical damage and obtaining functional recovery. C1 MCLEAN HOSP, MRC, NEUROREGENERAT LAB, BELMONT, MA 02178 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT NEUROSURG, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, PROGRAM NEUROSCI, BOSTON, MA 02114 USA. BOSTON UNIV, BOSTON, MA 02215 USA. DIACRIN INC, BOSTON, MA 02129 USA. NR 80 TC 22 Z9 23 U1 0 U2 2 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PD SEP-OCT PY 1995 VL 4 IS 5 BP 515 EP 527 DI 10.1016/0963-6897(95)00027-U PG 13 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA RW554 UT WOS:A1995RW55400010 PM 8520835 ER PT J AU HOOP, B BURTON, MD KAZEMI, H LIEBOVITCH, LS AF HOOP, B BURTON, MD KAZEMI, H LIEBOVITCH, LS TI CORRELATION IN STIMULATED RESPIRATORY NEURAL NOISE SO CHAOS LA English DT Article ID ACETYLCHOLINE; INVITRO; RAT AB Noise in spontaneous respiratory neural activity of the neonatal rat isolated brainstem-spinal cord preparation stimulated with acetylcholine (ACh) exhibits positive correlation. Neural activity from the C4 (phrenic) ventral spinal rootlet, integrated and corrected for slowly changing trend, is interpreted as a fractal record in time by rescaled range, relative dispersional, and power spectral analyses. The Hurst exponent H measured from time series of 64 consecutive signal levels recorded at 2 s intervals during perfusion of the preparation with artificial cerebrospinal fluid containing ACh at concentrations 62.5 to 1000 mu M increases to a maximum of 0.875+/-0.087 (SD) at 250 mu M ACh and decreases with higher ACh concentration. Corrections for bias in measurement of H were made using two different kinds of simulated fractional Gaussian noise. Within limits of experimental procedure and short data series, we conclude that in the presence of added ACh of concentration 250 to 500 mu M, noise which occurs in spontaneous respiratory-related neural activity in the isolated brainstem-spinal cord preparation observed at uniform time intervals exhibits positive correlation. (C) 1995 American Institute of Physics. C1 FLORIDA ATLANTIC UNIV,CTR COMPLEX SYST,BOCA RATON,FL 33431. RP HOOP, B (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED SERV,PULM & CRIT CARE UNIT,BOSTON,MA 02114, USA. NR 18 TC 12 Z9 12 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 1054-1500 J9 CHAOS JI Chaos PD SEP PY 1995 VL 5 IS 3 BP 609 EP 612 DI 10.1063/1.166130 PG 4 WC Mathematics, Applied; Physics, Mathematical SC Mathematics; Physics GA RV669 UT WOS:A1995RV66900013 ER PT J AU ROSENZWEIG, AC NORDLUND, P TAKAHARA, PM FREDERICK, CA LIPPARD, SJ AF ROSENZWEIG, AC NORDLUND, P TAKAHARA, PM FREDERICK, CA LIPPARD, SJ TI GEOMETRY OF THE SOLUBLE METHANE MONOOXYGENASE CATALYTIC DIIRON CENTER IN 2 OXIDATION-STATES (VOL 2, PG 409, 1995) SO CHEMISTRY & BIOLOGY LA English DT Correction DE CARBOXYLATE SHIFT; DINUCLEAR IRON CENTER; METHANE OXIDATION; METHYLOCOCCUS CAPSULATUS (BATH); X-RAY CRYSTALLOGRAPHY ID RIBONUCLEOTIDE REDUCTASE; HYDROXYLASE COMPONENT; CRYSTAL-STRUCTURE; PROTEIN; IDENTIFICATION; SUBSTRATE; COMPLEX; CYCLE; SITES AB Background: The hydroxylase component of soluble methane monooxygenase (sMMO) contains a dinuclear iron center responsible for the oxidation of methane to methanol. As isolated, the center is in the oxidized, diiron(III) state. The 2.2 Angstrom resolution X-ray structure of the oxidized hydroxylase, H-OX, from Methylococcus capsulatus (Bath) was previously determined at 4 degrees C. In this structure the two iron atoms are bridged by a glutamate, a hydroxide ion, and an acetate ion, and additionally coordinated Co two His residues, three Glu residues, and a water molecule. Results: The 1.7 Angstrom resolution crystal structures of the sMMO hydroxylase fi-om Methylococcus capsulatus (Bath) in both its oxidized diiron(III), H-OX and dithionite-treated, reduced diiron(II), H-red, oxidation states were determined at -160 degrees C. The structure of the diiron center in H-OX differs from that previously reported at 2.2 Angstrom resolution and 4 degrees C. Although the hydroxide bridge is retained, the bidentate, bridging ligand assigned as acetate is replaced by a weakly coordinating monoatomic water bridge. In the resulting four-membered Fe(OH)Fe(OH2) ring, the Fe ... Fe distance is shortened from 3.4 Angstrom to 3.1 Angstrom. In protomer A of H-red, the hydroxide bridge is displaced by an oxygen atom of Glu243, which undergoes a carboxylate shift from its terminal monodentate binding mode in H-OX to a mode in which the carboxylate is both monoatomic bridging and bidentate chelating. We therefore conclude that the center has been reduced to the diiron(II) oxidation state. Both iron atoms are coordinated to five ligands and weakly to a sixth water molecule in the resulting structure. The diiron center in protomer B of H-red has the same composition as those in H-OX. In both the oxidized and reduced structures, the diiron core is connected through hydrogen bonds involving exogenous species to Thr213 in the active site cavity. Conclusions: The diiron center in H-OX can change its exogenous ligand coordination and geometry, a property that could be important in the catalytic cycle of sMMO. In H-red, a carboxylate shift occurs, extruding hydroxide ion and opening coordination sites for reaction with O-2 to form the diiron(III) peroxo intermediate, H-peroxo. Residue Thr213 may function in catalysis. C1 UNIV STOCKHOLM, DEPT BIOL MOLEC, S-10691 STOCKHOLM, SWEDEN. MIT, DEPT CHEM, CAMBRIDGE, MA 02139 USA. RP ROSENZWEIG, AC (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DEPT BIOL CHEM & MOLEC PHARMACOL, 44 BINNEY ST, BOSTON, MA 02115 USA. NR 39 TC 5 Z9 5 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 EI 1879-1301 J9 CHEM BIOL JI Chem. Biol. PD SEP PY 1995 VL 2 IS 9 BP 632 EP + PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RY331 UT WOS:A1995RY33100011 ER PT J AU BOUROS, D PARE, P PANAGOU, P TSINTIRIS, K SIAFAKAS, N AF BOUROS, D PARE, P PANAGOU, P TSINTIRIS, K SIAFAKAS, N TI THE VARIED MANIFESTATION OF PULMONARY-ARTERY AGENESIS IN ADULTHOOD SO CHEST LA English DT Article DE BRONCHIECTASIS; BRONCHOGRAPHY; BRONCHOSCOPY; CONGENITAL ABNORMALITIES; HYPERLUCENT LUNG; LUNG SCAN; MRI; PULMONARY ARTERY; PULMONARY ARTERY AGENESIS; VASCULAR ABNORMALITIES ID UNILATERAL ABSENCE; OCCLUSION; VESSELS; LUNG AB Objective: Unilateral pulmonary artery agenesis (UPAA), a rare congenital anomaly that is frequently associated with other cardiovascular abnormalities, is usually diagnosed in childhood. Most patients who have no associated cardiac anomalies have only minor Or absent symptoms and survive into adulthood. The conditions of such patients are frequently misdiagnosed in adulthood. In this report, we describe six patients with UPAA in whom the diagnosis was first established in adulthood. The varied clinical presentation of these patients is reviewed and the relative effectiveness of a variety of diagnostic tests is compared. Subjects and methods: During the period January 1987 through December 1990, six male patients, aged 17 to 20 years, were found to have UPAA at the time of their medical screening for enrollment into the armed forces, The diagnosis was based on history, clinical and imaging examinations, including chest radiography, ventilation-perfusion lung scan, digital subtraction angiography (DSA), computed tomography (CT), and magnetic resonance imaging (MRI). Results: In four of the patients, the UPAA was on the left side and in two it was on the right A right aortic arch was present in three patients and other cardiovascular anomalies were found in three. Pulmonary function studies showed a mild restrictive pattern in four. In contrast to previous reports, the ventilation scan showed a diminished ''wash in'' and ''equilibrium'' phase without a delayed ''wash out'' phase on the affected side in all patients. Selective bronchography through the fiberoptic bronchoscope revealed ipsilateral mixed-type bronchiectasis in two of four patients studied a finding of clinical significance that has not been described previously. In all cases, the diagnosis was made by DSA. CT of the thorax (n=6) and MRI (n=4) were diagnostic in all cases in which they were performed, but added no significant information. Conclusion: UPAA is frequently misdiagnosed in adulthood and is often not considered in the differential diagnosis of the unilateral hyperlucent lung. Clinicians and radiologists should be aware of the possibility of undiagnosed cases in adults, with many atypical characteristics. C1 UNIV CRETE,SCH MED,DEPT THORAC MED,GR-71110 IRAKLION,GREECE. UNIV BRITISH COLUMBIA,ST PAULS HOSP,PULM RES LAB,VANCOUVER,BC V6T 1W5,CANADA. ARMY GEN HOSP,DEPT THORAC MED,ATHENS,GREECE. MASSACHUSETTS GEN HOSP,PULM UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI BOUROS, DEMOSTHENES/0000-0002-0685-0765 NR 27 TC 96 Z9 98 U1 1 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD SEP PY 1995 VL 108 IS 3 BP 670 EP 676 DI 10.1378/chest.108.3.670 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA RU348 UT WOS:A1995RU34800018 PM 7656614 ER PT J AU JELLINEK, MS LITTLE, M BENEDICT, K MURPHY, JM PAGANO, M POITRAST, F QUINN, D AF JELLINEK, MS LITTLE, M BENEDICT, K MURPHY, JM PAGANO, M POITRAST, F QUINN, D TI PLACEMENT OUTCOMES OF 206 SEVERELY MALTREATED CHILDREN IN THE BOSTON JUVENILE-COURT SYSTEM - A 7.5-YEAR FOLLOW-UP-STUDY SO CHILD ABUSE & NEGLECT LA English DT Article DE CHILD ABUSE AND NEGLECT; CARE AND PROTECTION PETITIONS; ADJUDICATION; FOSTER CARE ID SAMPLE; ABUSE; NEGLECT; PARENTS; FAMILY; INTERVENTION; MISTREATMENT; PREVALENCE; BEHAVIOR; FOSTER AB This study examines placement outcomes of 206 severely maltreated children 7.5 years after arraignment in Boston Juvenile Court (BJC) on Care and Protection Petitions. Sixty-seven percent (n = 138) of the sample had permanently removed from their parents and 33% (n = 68) had their cases dismissed in the BJC. At time of this follow-up, 21% of the full sample (n = 44) were still in temporary custody awaiting permanent placement. In addition, 4% (n = 8) of children had ''drifted'' back to their abusive/neglectful parents despite prior permanent removal. The average time children in this sample spent in probate proceedings (awaiting permanent placement) had increased substantially to 2.1 years since the last overview study of this sample 4 years ago. The rate of court referral for incidences of reabuse (a C&P filing), or delinquency was significantly lower among children who had been permanently placed (p < .003). Rates of court-referral for reabuse charges were the same (16%) for children who were in temporary custody at the time of follow-up and children who had been dismissed back to the parent for whom the original C&P had been filed. Results are discussed in light of the urgent need to restructure time limits in juvenile court proceedings, integrate adequate tracking of child abuse and neglect cases through and across court and agency boundaries, and the use standardized assessments of abused and neglected children as a tool in the adjudication process. C1 BOSTON JUVENILE COURT,BOSTON,MA. RP JELLINEK, MS (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,ACC 725,BOSTON,MA 02114, USA. NR 39 TC 8 Z9 8 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abus. Negl. PD SEP PY 1995 VL 19 IS 9 BP 1051 EP 1064 DI 10.1016/0145-2134(95)00067-I PG 14 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA RR084 UT WOS:A1995RR08400004 PM 8528812 ER PT J AU Firooz, A TehranchiNia, Z Ahmed, AR AF Firooz, A TehranchiNia, Z Ahmed, AR TI Benefits and risks of intralesional corticosteroid injection in the treatment of dermatological diseases SO CLINICAL AND EXPERIMENTAL DERMATOLOGY LA English DT Review ID CELL GROWTH-FACTOR; THERAPY; GLUCOCORTICOIDS; INVITRO; HYDROCORTISONE; COMPLICATION; ANAPHYLAXIS; PREDNISONE; INHIBITION; HEMANGIOMA AB Intralesional corticosteroid (CS) injections have been used to treat a variety of dermatological and non-dermatological diseases with variable results. The purpose of the injection is to attain a high concentration of the drug at the diseased site, with minimal systemic absorption. Several CS preparations are available for intralesional injection, although triamcinolone derivatives have gained the widest usage in dermatology. The dose and the interval between injections depend on the type, size and severity of the lesion as well as the response to the previous injections. The most critical issue in the efficacy and also in the development of complications of the injections, is the method of injection. Several local and systemic side-effects have been reported following intralesional injections, but most of them are rare or acceptable. Thus intralesional CS injection is an integral part of the clinical practice of dermatology. Since their introduction in 1951,(1) intralesional CS injections have become an integral part of clinical practice in dermatology. They are used alone or in combination with other therapeutic modalities in the treatment of many skin diseases. The purpose of the injection is to attain a high local concentration of the CS at the diseased site, without significant systemic absorption, thus avoiding the numerous side-effects associated with systemic administration. Intralesional CS injection may be a valuable therapeutic modality in situations where topical CS are not suitable for use, either because of low potency and inefficient epidermal barrier penetration or in clinical conditions associated with epidermal atrophy. C1 HARVARD UNIV,SCH DENT MED,DEPT ORAL MED & PATHOL,CTR BLOOD RES,BOSTON,MA 02115. FU NEI NIH HHS [EY08379]; NIDCR NIH HHS [DE09978] NR 79 TC 11 Z9 11 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0307-6938 J9 CLIN EXP DERMATOL JI Clin. Exp. Dermatol. PD SEP PY 1995 VL 20 IS 5 BP 363 EP 370 PG 8 WC Dermatology SC Dermatology GA TM905 UT WOS:A1995TM90500001 PM 8593711 ER PT J AU CASTLE, S WILKINS, S HECK, E TANZY, K FAHEY, J AF CASTLE, S WILKINS, S HECK, E TANZY, K FAHEY, J TI DEPRESSION IN CAREGIVERS OF DEMENTED PATIENTS IS ASSOCIATED WITH ALTERED IMMUNITY - IMPAIRED PROLIFERATIVE CAPACITY, INCREASED CD8(+), AND A DECLINE IN LYMPHOCYTES WITH SURFACE SIGNAL-TRANSDUCTION MOLECULES (CD38(+)) AND A CYTOTOXICITY MARKER (CD56(+) CD8+) SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE DEPRESSION; IMMUNE DYSFUNCTION; CD38; CD56; AGING ID KILLER-CELL-ACTIVITY; STRESS-INDUCED MODULATION; ACTIVATION; DISEASE; SUBSETS; AGE; SUPPRESSION; POPULATIONS; LEUKOCYTES AB Changes in relevant immune parameters, including function, were found to be associated with depression in elderly caregiver wives of demented patients. We studied the relationship between immune cell phenotype and T cell proliferative capacity of such caregivers to levels of stress and depression over the course of a support group intervention. The data indicate the strongest association between depression (of all stress parameters) and impaired T cell proliferative capacity. Depression was also most strongly (of stress parameters) associated with a shift in T cell populations with an increase in CD8(+) T cells, and a reduced percentage of CD38(+) cells in both CD8(+) and CD4(+) T cell populations. Since CD38 is a signal transduction factor, it was interesting that a decreased percentage of CD38(+) cells correlated with impaired T cell function (proliferation). Another significant difference was the reduction in natural killer (NK) cells as well as the percentage of the CD56(+) component of the CD8(+) population. This latter subset is important in MHC-unrestricted cytotoxicity, and has been found expanded in healthy centenarians. This study shows that both chronic stress, and depression in particular, and age have deleterious effects on T cells, and together could significantly contribute to the higher risk of disease and mortality associated with being a caregiver of a demented individual. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,CTR INTERDISCIPLINARY RES & IMMUNOL & DIS,LOS ANGELES,CA. RP CASTLE, S (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN 11G,LOS ANGELES,CA 90073, USA. FU NIA NIH HHS [AG00489-01] NR 42 TC 53 Z9 53 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD SEP PY 1995 VL 101 IS 3 BP 487 EP 493 PG 7 WC Immunology SC Immunology GA RR203 UT WOS:A1995RR20300017 PM 7545096 ER PT J AU ROSSETTI, RG SEILER, CM LAPOSATA, M ZURIER, RB AF ROSSETTI, RG SEILER, CM LAPOSATA, M ZURIER, RB TI DIFFERENTIAL REGULATION OF HUMAN T-LYMPHOCYTE PROTEIN-KINASE-C ACTIVITY BY UNSATURATED FATTY-ACIDS SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID INDEPENDENT MECHANISM; RHEUMATOID-ARTHRITIS; CELL GROWTH; ACTIVATION; CALPAIN; HETEROGENEITY; SUBSTRATE; FAMILY AB Administration of gamma-linolenic acid suppresses active synovitis in patients with rheumatoid arthritis. We therefore examined the effects of gamma-linolenic acid and its first metabolite, dihomo-gamma-linolenic acid, on protein kinase C, a key element in transduction of signals from cell surface to nucleus. We report here that gamma-linolenic acid and dihomo-gamma-linolenic acid suppress total protein kinase C activity, but facilitate translocation of protein kinase C activity from cytosol to membrane in human peripheral blood T lymphocytes stimulated with phorbol 12-myristate 13-acetate. Arachidonic acid and eicosapentaenoic acid do not influence total protein kinase C activity and have only modest effects on enzyme translocation. These findings in whole cells are in contrast to results of experiments performed with isolated protein kinase C, in which unsaturated fatty acids uniformly enhance protein kinase C activity, The differential effects of unsaturated fatty acids underscore the complexity of protein kinase C regulation and indicate that gamma-linolenic and dihomo-gamma-linolenic acids influence T lymphocyte protein kinase C metabolism in a manner that is unique among unsaturated fatty acid precursors of eicosanoids. (C) 1995 Academic Press, Inc. C1 UNIV MASSACHUSETTS,MED CTR,DEPT MED,DIV RHEUMATOL,WORCESTER,MA 01655. MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV CLIN LABS,BOSTON,MA 02114. FU NIAMS NIH HHS [AR38501]; NIDDK NIH HHS [DK43159] NR 24 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD SEP PY 1995 VL 76 IS 3 BP 220 EP 224 DI 10.1006/clin.1995.1119 PN 1 PG 5 WC Immunology; Pathology SC Immunology; Pathology GA RV957 UT WOS:A1995RV95700002 PM 7554442 ER PT J AU BARCHIESI, F HOLLIS, RJ DELPOETA, M MCGOUGH, DA SCALISE, G RINALDI, MG PFALLER, MA AF BARCHIESI, F HOLLIS, RJ DELPOETA, M MCGOUGH, DA SCALISE, G RINALDI, MG PFALLER, MA TI TRANSMISSION OF FLUCONAZOLE-RESISTANT CANDIDA-ALBICANS BETWEEN PATIENTS WITH AIDS AND OROPHARYNGEAL CANDIDIASIS DOCUMENTED BY PULSED-FIELD GEL-ELECTROPHORESIS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GENETIC SIMILARITY; STRAINS; THERAPY AB Electrophoretic karyotype and restriction endonuclease analysis of genomic DNA were used for the typing of nine isolates of Candida albicans from the oral cavities of two patients with AIDS-a husband and wife-whose infections became resistant to treatment with fluconazole (400 mg/d), The in vitro susceptibilities of sequential isolates to fluconazole and two other triazoles, itraconazole and the investigational drug D0870, were also evaluated. DNA analysis showed that the isolates responsible for fluconazole-resistant episodes of oropharyngeal candidiasis in the two patients were genetically related, In vitro susceptibility to fluconazole correlated well with clinical outcome, Although the minimal inhibitory concentrations of itraconazole and D0870 for fluconazole-resistant isolates were higher than those for fluconazole-susceptible isolates, both of the former triazoles exhibited good in vitro activity against the isolates tested. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV IOWA,COLL MED,DEPT PATHOL,CLIN MICROBIOL LAB,IOWA CITY,IA. UNIV ANCONA,IST MALATTIE INFETT & MED PUBL,ANCONA,ITALY. RP BARCHIESI, F (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,FUNGUS TESTING LAB,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 25 TC 34 Z9 35 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1995 VL 21 IS 3 BP 561 EP 564 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA RU940 UT WOS:A1995RU94000014 PM 8527544 ER PT J AU WEINRAUCH, LA DELIA, JA GLEASON, RE SHAFFER, D MONACO, AP AF WEINRAUCH, LA DELIA, JA GLEASON, RE SHAFFER, D MONACO, AP TI ROLE OF CALCIUM-CHANNEL BLOCKERS IN DIABETIC RENAL-TRANSPLANT PATIENTS - PRELIMINARY-OBSERVATIONS ON PROTECTION FROM SEPSIS SO CLINICAL NEPHROLOGY LA English DT Article DE CADAVERIC RENAL ALLOGRAFT; DIABETES; SEPSIS; CALCIUM CHANNEL BLOCKING AGENTS ID CORONARY-ARTERY DISEASE; SURVIVAL; MEDICARE AB Background: Diabetic recipients of kidney transplants have an excessively high risk of allograft loss, infectious complications with sepsis, cardiovascular events and early death. This study was designed in order to determine whether post-transplantation medical management influenced long-term results. Methods: Seventy consecutive diabetic recipients of cadaveric renal allografts were followed from the time of transplant. Treatment regimens were based on the clinical judgement of transplant nephrologists and surgeons, not by the study team. Patients were followed for 2 to 9 years (mean follow-up of 50.85 months, one lost to follow-up). Groups were classified by HLA match, type of immunosuppression, prior cardiovascular history, type of antihypertensives (36 on calcium channel blockers, 32 on beta blockers, 8 ACE inhibitors). Events were defined as myocardial infarction, CVA, graft loss with return to dialysis, life-threatening sepsis, or death. Results: Twenty allografts failed during the study, 24 patients died. Potentially cardioprotective drugs did not impact significantly on cardiac death, MI or CVA. Survivals were better when calcium channel blockers were used (mean 71.7 vs 38.6 months, p < 0.05; 4-year survival 84 vs 58%). When both beta and calcium channel blockers were used (n = 20), patient mean survival was 72.5 months vs 36.8 months for 21 patients who were not treated with blockers (p < 0.005). There was a lower incidence of graft loss when beta blockers and calcium channel blockers were used: at mean patient survival of 36.8 months, the no-blockers group had a mean graft survival of 19.3 months vs 72.5 months for blocker-treated patients (p < 0.002). Reinstitution of dialysis occurred less often with calcium channel blockers (17 vs 42%) or beta blockers (19 vs 38%) used either individually or together (5 vs 42%), all p < 0.05. Calcium channel blocker treated patients had 1/9 the number of septic deaths, fewer patients had multiple septic episodes, all p < 0.02. Conclusion: Allograft success and patient survivals may be improved and sepsis related events diminished when diabetic renal allograft recipients are treated with calcium channel blocking agents, plus or minus beta blockers. Considerable savings can be accomplished and graft results with these drugs can appraoch non-diabetic and live-related transplant results. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. DEACONESS HOSP,DEPT MED,BOSTON,MA. DEACONESS HOSP,DEPT SURG,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,BOSTON,MA 02115. MT AUBURN HOSP,BOSTON,MA. OI Weinrauch, Larry/0000-0003-1357-9528 NR 15 TC 11 Z9 11 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI MUNCHEN-DEISENHOFEN PA BAHNHOFSTRABE 9 POSTFACH 49, W-8024 MUNCHEN-DEISENHOFEN, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD SEP PY 1995 VL 44 IS 3 BP 185 EP 192 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA RV444 UT WOS:A1995RV44400007 PM 8556835 ER PT J AU SIMPSON, NS JUPITER, JB AF SIMPSON, NS JUPITER, JB TI COMPLEX FRACTURE PATTERNS OF THE UPPER EXTREMITY SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID HUMERAL SHAFT FRACTURES; LOCKING NAIL; EXTERNAL FIXATION; INJURIES; EXPERIENCE AB Combined skeletal injuries to the upper limb present complex management problems because they may result in dysfunction of the terminal unit of the upper limb-the hand. This article explores complex patterns of skeletal and soft tissue injuries, including complex soft tissue trauma with closed and open fractures; the floating shoulder, elbow, and forearm; and the role of skeletal fixation in conjunction with the complex fracture patterns. As the functional capacity of the upper limb reflects an integration of all its component parts, a combined approach to skeletal and soft tissue trauma is of fundamental importance in upper limb trauma. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED TRAUMA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ORTHOPAED SURG,BOSTON,MA. MASSACHUSETTS GEN HOSP,ORTHOPAED HAND SERV,BOSTON,MA 02114. NR 62 TC 16 Z9 18 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 1995 IS 318 BP 43 EP 53 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA RV243 UT WOS:A1995RV24300007 PM 7671531 ER PT J AU ORTIZCRUZ, EJ QUINN, RH FANBURG, JC ROSENBERG, AE MANKIN, HJ AF ORTIZCRUZ, EJ QUINN, RH FANBURG, JC ROSENBERG, AE MANKIN, HJ TI LATE DEVELOPMENT OF A MALIGNANT FIBROUS HISTIOCYTOMA AT THE SITE OF A GIANT-CELL TUMOR SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID RADIATION-THERAPY; BONE AB A case of late development of a high grade malignant fibrous histiocytoma at the site of a previously surgically treated giant cell tumor is reported, The patient initially was treated for a benign giant cell tumor of the lateral condyle of the distal femur by curettage, implant of auto- and allograft bone, but no radiation. Eighteen years later, he noted progressively increasing pain and disability, Radiographs showed some change, but magnetic resonance imaging clearly disclosed a tumor arising at the site and extending outside the bone, After chemotherapy, the tumor was resected and histologically showed no evidence of a recurrent giant cell tumor, only a high grade malignant fibrous histiocytoma. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ORTHOPED SURG,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. OI ORTIZ CRUZ, EDUARDO J./0000-0002-1405-0688 NR 35 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 1995 IS 318 BP 199 EP 204 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA RV243 UT WOS:A1995RV24300026 PM 7671517 ER PT J AU OKEEFE, RJ OCONNELL, JX TEMPLE, HT SCULLY, SP KATTAPURAM, SV SPRINGFIELD, DS ROSENBERG, AE MANKIN, HJ AF OKEEFE, RJ OCONNELL, JX TEMPLE, HT SCULLY, SP KATTAPURAM, SV SPRINGFIELD, DS ROSENBERG, AE MANKIN, HJ TI CALCIFIC MYONECROSIS - A LATE SEQUELA TO COMPARTMENT SYNDROME OF THE LEG SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MYOSITIS-OSSIFICANS; FEATURES; SARCOMA AB The clinicopathologic features of calcific myonecrosis are presented from results of an examination of 3 cases of this rare syndrome and review of the literature, Calcific myonecrosis is a painful, expansile, calcified mass that develops in muscle several decades after lower extremity trauma that typically has been associated with vascular injury, Plain radiographs show a well-defined and heavily calcified mass replacing the leg musculature. The calcifications are present in a thin, linear pattern and are organized around the periphery of the lesion, Smooth erosion of the adjacent bone may be present, whereas magnetic resonance imaging shows a heterogeneous signal with enhancement limited to the periphery of the mass, Pathologic features consist of a centrally cystic mass arising in muscle filled with friable, tan to dark red, soft debris, The cyst walls are firm and fibrous and contain many needle-like, elongated, calcified shards of necrotic tissue composed of hypocellular fibrous tissue with focal aggregates of hemosiderin-laden macrophages. The cyst contents are composed of necrotic skeletal muscle and acellular amorphous debris containing many cholesterol crystals, fibrin, and recent hemorrhage, including focal aggregates of organizing thrombus, The pathologic findings suggest that calcific myonecrosis might expand with time by virtue of recurrent intralesional hemorrhage into a chronic calcified mass that eventually becomes symptomatic, Surgical intervention is associated with a high rate of complication, particularly in cases in which intralesional procedures have been done. C1 VANCOUVER GEN HOSP,DEPT PATHOL,VANCOUVER,BC V5Z 1M9,CANADA. WALTER REED ARMY MED CTR,DEPT ORTHOPAED,WASHINGTON,DC 20307. DUKE UNIV,MED CTR,DEPT ORTHOPAED,DURHAM,NC. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ORTHOPAED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP OKEEFE, RJ (reprint author), UNIV ROCHESTER,MED CTR,DEPT ORTHOPAED,BOX 665,ROCHESTER,NY 14642, USA. NR 15 TC 27 Z9 29 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD SEP PY 1995 IS 318 BP 205 EP 213 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA RV243 UT WOS:A1995RV24300027 PM 7671519 ER PT J AU KROSNICK, A AF KROSNICK, A TI EDITORIAL COMMENT SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP KROSNICK, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BELLE MEAD PA 105 RAIDER BLVD, BELLE MEAD, NJ 08502 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP-OCT PY 1995 VL 17 IS 5 BP 799 EP 799 DI 10.1016/0149-2918(95)80057-3 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TE580 UT WOS:A1995TE58000001 ER PT J AU KROSNICK, A AF KROSNICK, A TI EDITORIAL COMMENT SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP KROSNICK, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BELLE MEAD PA 105 RAIDER BLVD, BELLE MEAD, NJ 08502 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD SEP-OCT PY 1995 VL 17 IS 5 BP 811 EP 811 DI 10.1016/0149-2918(95)80059-X PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TE580 UT WOS:A1995TE58000003 ER PT J AU HURFORD, WE FAVORITE, F AF HURFORD, WE FAVORITE, F TI ASSOCIATION OF MYOCARDIAL-ISCHEMIA WITH FAILURE TO WEAN FROM MECHANICAL VENTILATION SO CRITICAL CARE MEDICINE LA English DT Article DE ELECTROCARDIOGRAPHY, CONTINUOUS; RESPIRATORY INSUFFICIENCY; OUTCOME ASSESSMENT; CRITICAL CARE; LUNGS; VENTILATORS, MECHANICAL; MYOCARDIAL ISCHEMIA; VENTILATOR WEANING; LENGTH OF HOSPITAL STAY ID PERIPHERAL VASCULAR-SURGERY; INTRA-THORACIC PRESSURE; ASSISTED VENTILATION; CHARGES AB Objective: To determine if myocardial ischemia, as detected by continuous electrocardiographic monitoring, is correlated with continued ventilator dependence in patients who have had difficulties weaning from mechanical ventilation. Design: A prospective, observational study, Setting: A university, tertiary care hospital, Patients: Seventeen medical and postsurgical patients (age 70 +/- 9 yrs; range 54 to 84) who had received mechanical ventilation for 5 to 67 days at the time of entry into the study, Interventions: None, Measurements and Main Results: Patients wore a calibrated, frequency-modulated, two-channel electrocardiographic recorder with two bipolar chest leads attached to exploring electrodes for 24 hrs, We recorded the following data: a) electrocardiographic evidence of myocardial ischemia; b) eventual separation from mechanical ventilation; c) whether the patient survived to be discharged from the hospital; d) duration of tracheal intubation and mechanical ventilation; and e) length of hospital stay, The key outcome variable tested was successful weaning, which was defined as breathing without mechanical ventilatory assistance on discharge from the hospital, Six (35%) of 17 patients had electrocardiographic evidence of myocardial ischemia at the time of entry into the study, The presence of ischemia was associated with failure to wean from mechanical ventilation (p < .05; relative risk 3.05), Conclusions: Myocardial ischemia (as detected by a 24-hr, continuous Holter monitor) occurs frequently in ventilator-dependent patients, The occurrence of ischemia was associated with failure to wean from mechanical ventilation in this patient population. RP HURFORD, WE (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT ANESTHESIA, BOSTON, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 15 TC 42 Z9 45 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1995 VL 23 IS 9 BP 1475 EP 1480 DI 10.1097/00003246-199509000-00006 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA RU202 UT WOS:A1995RU20200006 PM 7664548 ER PT J AU STACK, AM SALADINO, RA THOMPSON, C SATTLER, F WEINER, DL PARSONNET, J NARIUCHI, H SIBER, GR FLEISHER, GR AF STACK, AM SALADINO, RA THOMPSON, C SATTLER, F WEINER, DL PARSONNET, J NARIUCHI, H SIBER, GR FLEISHER, GR TI FAILURE OF PROPHYLACTIC AND THERAPEUTIC USE OF A MURINE ANTITUMOR NECROSIS FACTOR MONOCLONAL-ANTIBODY IN ESCHERICHIA-COLI SEPSIS IN THE RABBIT SO CRITICAL CARE MEDICINE LA English DT Article DE SEPSIS; TUMOR NECROSIS FACTOR; MONOCLONAL ANTIBODY; ENDOTOXIN; SEPTIC SHOCK; CYTOKINES; BACTERIAL INFECTION; ANTIBIOTIC THERAPY; PERITONITIS; CRITICAL ILLNESS ID NEGATIVE BACTERIAL SEPSIS; SEPTIC SHOCK; FACTOR-ALPHA; CACHECTIN; EFFICACY; ENDOTOXIN; INTERLEUKIN-1; PERITONITIS; PREVENTION; CYTOKINES AB Objective: To determine the efficacy of a murine anti-tumor necrosis factor (TNF) monoclonal antibody in the treatment of Escherichia coli peritonitis and sepsis in the rabbit. Design: Prospective, paired, randomized, blinded, controlled animal trial. Setting: Animal research laboratory, Subjects: Male New Zealand white rabbits, Interventions: Anesthetized rabbits were cannulated with indwelling femoral arterial and venous catheters, Peritonitis and sepsis were induced by intraperitoneal challenge using live E, coli O18ac bacteria, All animals were treated with gentamicin and ceftriaxone 1 hr after challenge, One group (prophylaxis experiment) consisting of ten rabbit pairs (the prophylaxis group), was treated with either murine anti-TNF monoclonal antibody or an equivalent volume of 5% albumin 3 hrs before E. coli challenge, A second group (therapeutic experiment) of 17 rabbit pairs, the treatment group, was also treated with murine anti-TNF monoclonal antibody or albumin control 1 hr after E, coli challenge, Measurements and Main Results: All animals were bacteremic 1 hr after challenge, Physiologic measures of sepsis (heart rate, mean arterial pressure, serum bicarbonate, and arterial pH) did not differ between control, prophylaxis, and treatment groups, Peak serum TNF concentration was significantly (p < .01) lower in animals receiving anti-TNF monoclonal antibody, in both the prophylaxis and treatment groups, than in control animals, The survival rate was not improved significantly in either the prophylaxis or treatment group, Conclusions: Prophylactic and therapeutic use of anti-TNF monoclonal antibody in a rabbit model of E, coli peritonitis and sepsis significantly lowers TNF concentrations but does not ameliorate the physiolose effects of sepsis and does not significantly improve survival. C1 DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA 02115. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,HANOVER,NH 03756. UNIV TOKYO,TOKYO,JAPAN. RP STACK, AM (reprint author), CHILDRENS HOSP,DIV EMERGENCY MED,BOSTON,MA, USA. NR 23 TC 24 Z9 25 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD SEP PY 1995 VL 23 IS 9 BP 1512 EP 1518 DI 10.1097/00003246-199509000-00011 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA RU202 UT WOS:A1995RU20200011 PM 7664553 ER PT J AU TAKAGI, C KING, GL CLERMONT, AC CUMMINS, DR TAKAGI, H BURSELL, SE AF TAKAGI, C KING, GL CLERMONT, AC CUMMINS, DR TAKAGI, H BURSELL, SE TI REVERSAL OF ABNORMAL RETINAL HEMODYNAMICS IN DIABETIC RATS BY ACARBOSE, AN ALPHA-GLUCOSIDASE INHIBITOR SO CURRENT EYE RESEARCH LA English DT Article DE ACARBOSE; HEMODYNAMICS; RETINA; DIABETES; RATS ID LIGHT ENTOPTIC PHENOMENON; BLOOD-FLOW; GLUCOSIDEHYDROLASE INHIBITOR; FLUORESCEIN ANGIOGRAPHY; GLYCEMIC CONTROL; CIRCULATION; MELLITUS; HYPERGLYCEMIA; RETINOPATHY; SUCROSE AB Acarbose is an inhibitor of intestinal alpha-glucosidase and has been reported to decrease blood glucose concentrations and glycosuria in diabetic patients and animals. In this study we investigated whether this drug could prevent the abnormalities detected in retinal circulation of diabetic rats. Longitudinal paired studies were performed and the changes in retinal circulation were analyzed using video based fluorescein angiography (VFA) methodology in the same animal. Baseline VFA recordings were obtained from 41 rats. These rats were separated into 4 different groups: In group A (n = 12), diabetes was induced by streptozotocin (STZ) injection and the rats were fed with acarbose (40 mg/100 g powdered chow) mixed into regular rat chow; In group B (n = 10), diabetes was induced by STZ injection and the rats were fed with normal chow; Tn group C (n = 9), the non-diabetic rats were fed with acarbose; In group D (n = 10), the non-diabetic rats were fed with normal chow. At the end of 2 weeks, all rats again underwent VFA recordings. Blood glucose levels and body weights of rats were monitored during the experiment. The mean blood glucose concentration of Group B was raised from 98.5 +/- 8.7 to 342 +/- 30 mg/dl after STZ injection while in Group A, this change in glucose level was partially ameliorated by acarbose (from 102 +/- 15 to 247 +/- 48 mg/dl). In Group C and D, the blood glucose levels were not significantly changed during the experiment. In Group B, a paired t-test analysis demonstrated that retinal blood flow in the untreated diabetic rats decreased significantly (p = 0.0001) 2 weeks after induction of diabetes (76.4 +/- 24.1 pixel(2)/s) compared to baseline (141.3 +/- 20.3 pixel(2)/s). In contrast, the acarbose treated diabetic rats in Group A showed no significant differences between blood flow before (140.1 +/- 21.6 pixel(2)/s) and after induction of diabetes (133.4 +/- 16.5 pixel(2)/s). There were no significant changes in retinal blood flow in the non-diabetic rat groups (Group C acarbose fed and Group D normal chow). These results suggest that acarbose can prevent the abnormalities detected in retinal circulation probably associated with decreasing the blood glucose concentration. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. NR 46 TC 22 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD SEP PY 1995 VL 14 IS 9 BP 741 EP 749 DI 10.3109/02713689508995795 PG 9 WC Ophthalmology SC Ophthalmology GA RW141 UT WOS:A1995RW14100001 PM 8529412 ER PT J AU BAILEY, SR KIESZ, RS AF BAILEY, SR KIESZ, RS TI INTRAVASCULAR STENTS - CURRENT APPLICATIONS - INTRODUCTION SO CURRENT PROBLEMS IN CARDIOLOGY LA English DT Review ID LUMINAL CORONARY ANGIOPLASTY; ANGIOGRAPHIC FOLLOW-UP; SAPHENOUS-VEIN GRAFTS; PALMAZ-SCHATZ STENTS; EXPANDABLE INTRACORONARY STENTS; 1985-1986 NATIONAL-HEART; VENOUS BYPASS GRAFTS; SMOOTH-MUSCLE CELLS; BALLOON ANGIOPLASTY; BLOOD-INSTITUTE C1 AUDIE L MURPHY MEM VET ADM MED CTR,CARDIAC CATHETERIZAT LAB,SAN ANTONIO,TX 78284. RP BAILEY, SR (reprint author), UNIV TEXAS HOSP,CARDIAC CATHETERIZAT LAB,GALVESTON,TX 77550, USA. NR 184 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0146-2806 J9 CURR PROB CARDIOLOGY JI Curr. Probl. Cardiol. PD SEP PY 1995 VL 20 IS 9 BP 618 EP & PG 0 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RV228 UT WOS:A1995RV22800002 ER PT J AU MATSUYAMA, SS YAMAGUCHI, DT VERGARA, J JARVIK, LF AF MATSUYAMA, SS YAMAGUCHI, DT VERGARA, J JARVIK, LF TI TETRAETHYLAMMONIUM-INDUCED CALCIUM-CONCENTRATION CHANGES IN SKIN FIBROBLASTS FROM PATIENTS WITH ALZHEIMER-DISEASE SO DEMENTIA LA English DT Article DE ALZHEIMER DISEASE; POTASSIUM CHANNEL; FIBROBLASTS; CALCIUM; DIAGNOSIS ID POTASSIUM-CHANNEL BLOCKERS; OSTEOBLAST-LIKE CELLS; WORK AB Potassium (Kc) channel dysfunction in fibroblasts was recently proposed as a potential diagnostic marker for Alzheimer disease (AD), We utilized a microspectrofluorometric method with Fura-2AM to measure intracellular free calcium ([Ca2+](i)) following depolarization with the K+ channel blocker tetraethylammonium (TEA) in seven AD and seven control fibroblast cultures, Contrary to our expectation, 43% of the AD and 36% of the control fibroblast plated coverglasses responded with an increase in [Ca2+](i) on addition of 100 mM TEA. The data suggest that the TEA-elicited [Ca2+](i) response is not a useful AD screening test. C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PHYSIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP MATSUYAMA, SS (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,PSYCHOGERIATR LAB B151R,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NIA NIH HHS [P30 AG10123] NR 11 TC 11 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1013-7424 J9 DEMENTIA JI Dementia PD SEP-OCT PY 1995 VL 6 IS 5 BP 241 EP 244 DI 10.1159/000106953 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA RU300 UT WOS:A1995RU30000001 PM 8528369 ER PT J AU KLEIN, RL LAIMINS, M LOPESVIRELLA, MF AF KLEIN, RL LAIMINS, M LOPESVIRELLA, MF TI ISOLATION, CHARACTERIZATION, AND METABOLISM OF THE GLYCATED AND NONGLYCATED SUBFRACTIONS OF LOW-DENSITY LIPOPROTEINS ISOLATED FROM TYPE-I DIABETIC-PATIENTS AND NONDIABETIC SUBJECTS SO DIABETES LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; OXIDATIVE MODIFICATION; INVITRO OXIDATION; ENHANCED SUSCEPTIBILITY; BEZAFIBRATE THERAPY; GLYCOSYLATION; NORMALIZATION; IDENTIFICATION; HETEROGENEITY; FIBROBLASTS AB The total low-density lipoprotein (LDL) fraction was isolated from 21 patients with type I diabetes and 7 nondiabetic normolipemic subjects. The LDL was separated into two subfractions, one glycated (G-LDL) and one nonglycated (N-LDL), using affinity chromatography. G-LDL comprised 21.1 +/- 3.6 and 5.2 +/- 0.6% of the total LDL in diabetic patients and normal subjects, respectively. G-LDL isolated from both diabetic patients and normal subjects was significantly more glycated than N-LDL isolated from the same subject. G-LDL isolated from both diabetic patients and normal subjects was enriched in triglycerides. The metabolism of N-LDL and G-LDL was investigated in human fibroblasts, which express only the classical LDL receptor, and in human monocyte-derived macrophages, which also express a receptor for G-LDL. In fibroblasts, the rates of receptor-mediated accumulation of N-LDL isolated from normal subjects and diabetic patients were significantly greater (P < 0.01) than those of G-LDL. In contrast, when the same LDL subfractions were incubated with human monocyte-derived macrophages, the rates of receptor-mediated accumulation of G-LDL isolated from both groups were significantly greater (P < 0.01) than those of N-LDL. Rates of degradation of G-LDL by human macrophages were not significantly different hom those of N-LDL during short-term incubations but reached statistical significance (P < 0.05) when LDL subfractions were incubated with cells for 24 h. G-LDL stimulated cholesteryl ester synthesis rates in human macrophages significantly (P < 0.05) more than N-LDL from the same subject and thus may contribute to the increased prevalence of atherosclerosis in diabetic patients. RP KLEIN, RL (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,RES SERV,109 BEE ST,CHARLESTON,SC 29401, USA. NR 42 TC 79 Z9 80 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1995 VL 44 IS 9 BP 1093 EP 1098 DI 10.2337/diabetes.44.9.1093 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TD623 UT WOS:A1995TD62300014 PM 7657034 ER PT J AU HUANG, R GUO, J LI, XP FAUSTMAN, DL AF HUANG, R GUO, J LI, XP FAUSTMAN, DL TI ELIMINATION OF SELF-PEPTIDE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I REACTIVITY IN NOD AND BETA(2)-MICROGLOBULIN-NEGATIVE MICE SO DIABETES LA English DT Article ID NONOBESE DIABETIC MICE; BETA-2-MICROGLOBULIN DEFICIENT MICE; CYTOTOXIC T-CELLS; ANTIGEN PRESENTATION; VIRUS-INFECTION; MHC; PREVENTION; PROTEIN; REGION; MOUSE AB Nonobese diabetic (NOD) mice and beta(2)-microglobulin-gene-ablated mice (beta(2)M -/-) show impaired presentation of major histocompatibility complex (MHC) class I and self-peptides, structures now recognized as critical for T-cell education to endogenous peptides. The naturally occurring NOD class I presentation abnormality appears to be attributable to, in part, a quantitative defect in the production of Tap-1 mRNA; Tap-1 with Tap-a normally functions as a transporter for stable self-peptide and class I assembly. This study attempts to reverse NOD and beta(2)M -/- mouse autoreactivity by introduced or reestablished syngeneic class I presentation. Introduction of MHC class I and self-peptides on syngeneic MHC class I-matched cells specifically prevented diabetes in NOD mice and eliminated in vitro class I-directed T-cell autoreactivity in NOD and beta(2)M -/- mice. Reestablishment of endogenous class I and self-peptide presentation in NOD mice was achieved with two well-described cures for the NOD mouse, complete Freund's adjuvant and mouse hepatitis virus. Both treatments induced Tap-1 mRNA, reestablished class I presentation of endogenous antigens, and eliminated in vitro and in vivo T-cell autoreactivity to self-peptides in the class I groove. These results substantiate a therapeutic role of self-peptide complexed with class I for T-cell education and suggest that some well-described NOD treatments may work, in part, through reestablishment of tolerance through class I and self-peptide. C1 MASSACHUSETTS GEN HOSP EAST,DIABET UNIT,IMMUNOBIOL LAB,BOSTON,MA. NR 42 TC 9 Z9 9 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1995 VL 44 IS 9 BP 1114 EP 1120 DI 10.2337/diabetes.44.9.1114 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TD623 UT WOS:A1995TD62300017 PM 7657037 ER PT J AU DIGNASS, AU PODOLSKY, DK RACHMILEWITZ, D AF DIGNASS, AU PODOLSKY, DK RACHMILEWITZ, D TI NOX GENERATION BY CULTURED SMALL-INTESTINAL EPITHELIAL-CELLS SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE NITRIC OXIDE; SMALL INTESTINE; EPITHELIAL CELLS ID NITRIC-OXIDE SYNTHASE; GROWTH-FACTOR-BETA; L-ARGININE; RAT; EXPRESSION; DAMAGE; INDUCTION; SECRETION; RECEPTORS; MOUSE AB The effect of cytokines, growth factors, mitogens, and bacterial products on nitric oxide (NO) generation by monolayers of small intestinal epithelial cells-6 (IEC-6) cells was evaluated. Subconfluent IEC-6 cells were maintained in DMEM containing 5% fetal calf serum and after 16-24 hr of incubation, the medium was replaced with fresh medium in the presence or absence of calcium ionophore (CaI), L-NAME, L-NNA, individual growth factors, cytokines, or mitogens. After 72 hr of culture, the media supernatant was collected and NOx generation was determined. NO synthase activity was determined in sonicated supernatants of IEC-6 cells by [C-14] arginine conversion to citrulline. NOx generation in subconfluent cultures was greater than in fully confluent cultures, suggesting contact inhibition. NOx generation by IEC-6 cells was significantly increased by CaI and inhibited by L-NAME and L-NNA. LPS, IL-1 beta, IL-2, IL-8, IFN-8, TFN-alpha, EGF, TGF-alpha, bFGF, and PHA significantly increased NOx generation. NO synthase activity in IEC-6 cells (4.2 +/- 1.7 pmol/min/10(6) cells) was NADPH dependent. These results suggest that stimulation of NOx generation by intestinal epithelial cells through cytokine bacterial products and mitogens may be one of the mechanisms responsible for their effects in the intestinal tract. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR INFLAMMATORY BOWEL DIS,BOSTON,MA. FU NIDDK NIH HHS [5P30 DK 43351] NR 35 TC 37 Z9 37 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD SEP PY 1995 VL 40 IS 9 BP 1859 EP 1865 DI 10.1007/BF02208647 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RX563 UT WOS:A1995RX56300002 PM 7555434 ER PT J AU ROSENBEK, JC AF ROSENBEK, JC TI EFFICACY IN DYSPHAGIA SO DYSPHAGIA LA English DT Article; Proceedings Paper CT 3rd Annual Meeting of the Dysphagia-Research-Society CY OCT 14-16, 1994 CL MCLEAN, VA SP Dysphagia Res Soc DE DYSPHAGIA; TREATMENT; EFFICACY; SWALLOWING THERAPY; DEGLUTITION; DEGLUTITION DISORDERS AB Data demonstrating the efficacy of behavioral methods for treating dysphagia are in short supply. This paper defines efficacy and distinguishes it from efficiency. It highlights the attitudes,measures, decisions, and data essential to the design of clinical trials. The need for additional outcome measures and for establishing appropriate treatment intensities are emphasized. RP ROSENBEK, JC (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT SPEECH PATHOL & AUDIOL,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 22 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD FAL PY 1995 VL 10 IS 4 BP 263 EP 267 DI 10.1007/BF00431420 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA RZ393 UT WOS:A1995RZ39300009 PM 7493508 ER PT J AU NOVICK, GE NOVICK, CC YUNIS, J YUNIS, E MARTINEZ, K DUNCAN, GG TROUP, GM DEININGER, PL STONEKING, M BATZER, MA HERRERA, RJ AF NOVICK, GE NOVICK, CC YUNIS, J YUNIS, E MARTINEZ, K DUNCAN, GG TROUP, GM DEININGER, PL STONEKING, M BATZER, MA HERRERA, RJ TI POLYMORPHIC HUMAN SPECIFIC ALU INSERTIONS AS MARKERS FOR HUMAN IDENTIFICATION SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 3rd International Conference on DNA Fingerprinting CY DEC 13-16, 1994 CL HYDERABAD, INDIA DE ALU REPEATS; POPULATION GENETICS; PATERNITY TESTING ID DNA-SEQUENCES; HUMAN GENOME; REPETITIVE ELEMENTS; FAMILY; EVOLUTION; AMPLIFICATION; REPEATS; GENES AB Alu sequences represent the largest family of short interspersed repetitive elements (SINEs) in humans with 500 000 copies per genome. Recently, one Alu subfamily was found to be human specific (HS). We originally described the use of polymorphic PIS Alu insertions as a tool in population studies and recently as tools in DNA fingerprinting and forensic analysis. In this report, we will use this simple polymerase chain reaction (PCR) base technique for the detection of HS Alu insertion polymorphisms. We will test the resolving power of this DNA profiling approach in both population genetics and paternity assessment. At the population level, we will describe the genotypic distribution of five polymorphic Alu insertions among 3 populations from the American continent, one of African origin, the other two Amerindians. Insight into their relationships will be provided. At the family level, we will examine one European American family of seven individuals and the same pedigree will also be characterized by way of the two systems currently and widely used to ascertain paternity: PCR-sequence specific oligonucleotide probe hybridization (PCR-SSO) and PCR-restriction fragment length polymorphism (PCR-RFLP) of human leucocyte antigen (HLA) class II molecules, and a standard RFLP protocol used in forensic casework and paternity studies. The importance and strengths of the method as well as its perspectives for future use in filiation studies will be evaluated. C1 FLORIDA INT UNIV,DEPT BIOL SCI,MIAMI,FL 33199. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,CAMBRIDGE,MA 02138. UNIV NACL COLOMBIA,INST GENET,BOGOTA,COLOMBIA. UNIV NEW MEXICO,SCH MED,DEPT PATHOL,ALBUQUERQUE,NM 87131. LOUISIANA STATE UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,BATON ROUGE,LA 70803. PENN STATE UNIV,DEPT ANTHROPOL,UNIVERSITY PK,PA 16802. LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,CTR HUMAN GENOME,LIVERMORE,CA 94550. OI Deininger, Prescott/0000-0002-1067-3028 FU CGH CDC HHS [GH00770, GH00340]; NCRR NIH HHS [RR08205] NR 35 TC 39 Z9 40 U1 0 U2 32 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP PY 1995 VL 16 IS 9 BP 1596 EP 1601 DI 10.1002/elps.11501601263 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA TD110 UT WOS:A1995TD11000009 PM 8582340 ER PT J AU GUO, J IIDAKLEIN, A HUANG, XW ABOUSAMRA, AB SEGRE, GV BRINGHURST, FR AF GUO, J IIDAKLEIN, A HUANG, XW ABOUSAMRA, AB SEGRE, GV BRINGHURST, FR TI PARATHYROID-HORMONE (PTH)/PTH-RELATED PEPTIDE RECEPTOR DENSITY MODULATES ACTIVATION OF PHOSPHOLIPASE-C AND PHOSPHATE-TRANSPORT BY PTH IN LLC-PK1 CELLS SO ENDOCRINOLOGY LA English DT Article ID OSTEOBLAST-LIKE CELLS; BETA-GAMMA-SUBUNITS; CALCITONIN RECEPTOR; EXPRESSION CLONING; ADENYLYL CYCLASE; PROTEIN-KINASE; KIDNEY-CELLS; CAMP; STIMULATION; CALCIUM AB We showed previously that a single species of cloned PTH/PTH-related peptide (PTHrP) receptors, when stably expressed in LLC-PK1 kidney cells, couples to multiple second messenger signals and biological responses. To address the linkages of individual messenger signals to specific biological responses in these cells, we examined the relations among PTH/PTHrP receptor expression, PTH-activated phospholipase C (PLC) and adenylyl cyclase, and PTH-regulated phosphate transport in LLC-PK1 cells that stably express cloned rat PTH/PTHrP receptors. Among 18 such subclones, PTH stimulation of intracellular cAMP accumulation was nearly equivalent, despite differences in receptor density ranging from 20,000-400,000 sites/cell. In contrast, activation of PLC by PTH was directly and continuously dependent upon receptor density. PTH-stimulated phosphate uptake also was strongly dependent upon receptor expression, correlated well with PLC activity, was mimicked by active phorbol esters but not by cAMP analogs or forskolin, and was strikingly inhibited by the protein kinase C inhibitor, staurosporine. The peptide analog [Arg(2)]human PTH-(1-34), which significantly stimulated cAMP accumulation but failed to activate PLC, also did not increase phosphate uptake. We conclude that in LLC-PK1 cells, PTH-modulated PLC activation, unlike adenylyl cyclase activation, is strongly dependent upon PTH/PTHrP receptor density. This feature is reflected in the analogous relation between receptor density and PTH regulation of phosphate uptake, which appears to be mediated via a PKC-dependent pathway in these transfected cells. The results suggest that regulation of PTH/PTHrP receptor expression on target cells may provide a mechanism for altering the character as well as the magnitude of the signaling response to the hormone. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. RP GUO, J (reprint author), MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, FRUIT ST, BOSTON, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 21 TC 58 Z9 58 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1995 VL 136 IS 9 BP 3884 EP 3891 DI 10.1210/en.136.9.3884 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RQ622 UT WOS:A1995RQ62200026 PM 7649096 ER PT J AU HU, H KOTHA, S BRENNAN, T AF HU, H KOTHA, S BRENNAN, T TI THE ROLE OF NUTRITION IN MITIGATING ENVIRONMENTAL INSULTS - POLICY AND ETHICAL ISSUES SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Symposium on Preventing Child Exposures to Environmental Hazards - Research and Policy Issues CY MAR 18-19, 1994 CL WASHINGTON, DC SP Childrens Environm Hlth Network, NIEHS, Univ Calif Berkeley, Sch Public Hlth Superfund Basic Res Program, Calif Dept Hlth Serv, W Alton Jones Fdn, Med Univ S Carolina, Environm Hazards Assessment Program, US EPA, Ctr Dis Control & Prevent, David and Lucile Packard Fdn, Calif Public Hlth Fdn, Impact Assessment Inc, March Dimes Birth Defects Fdn, Teratol Soc DE NUTRITION; ENVIRONMENT; TOXICOLOGY; LEAD; CALCIUM; PREVENTION; JUSTICE; DIET ID LEAD MOBILIZATION; DIETARY CALCIUM; BLOOD LEAD; ABSORPTION; RATS; RETINOIDS; PREGNANCY; CRITIQUE; CADMIUM; WOMEN C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT GENITOURINARY ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA 02115. OI Hu, Howard/0000-0002-3676-2707 FU NIEHS NIH HHS [ES00002, P42-ES05947, R01-ES05257-01A1] NR 55 TC 7 Z9 8 U1 1 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD SEP PY 1995 VL 103 SU 6 BP 185 EP 190 DI 10.2307/3432372 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA TB481 UT WOS:A1995TB48100037 PM 8549471 ER PT J AU SIMPSON, SJ MIZOGUCHI, E ALLEN, D BHAN, AK TERHORST, C AF SIMPSON, SJ MIZOGUCHI, E ALLEN, D BHAN, AK TERHORST, C TI EVIDENCE THAT CD4(+), BUT NOT CD8(+) T-CELLS ARE RESPONSIBLE FOR MURINE INTERLEUKIN-2-DEFICIENT COLITIS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD4(+) T CELL; ULCERATIVE COLITIS; CYTOTOXIC T CELL ID INFLAMMATORY BOWEL-DISEASE; CHRONIC INTESTINAL INFLAMMATION; RECEPTOR MUTANT MICE; INTRAEPITHELIAL LYMPHOCYTES; EPITHELIAL-CELLS; ULCERATIVE-COLITIS; GUT; ANTIGEN; DIFFERENTIATION; EXPRESSION AB Mice deficient in interleukin-2 production (IL-2(null) mice) develop colonic inflammation closely resembling ulcerative colitis in humans. Although this disease is marked by substantial infiltration of the colon by CD8(+) and CD4(+) T lymphocytes, no function has yet been assigned to these T cell subsets in the development of colitis in the IL-2(null) mouse. For the present study, we investigated the involvement of T lymphocytes in the onset of colitis in IL-2(null) mice, and examined the possible role played by cytotoxic T cells. Both lamina propria lymphocytes (LPL) and intraepithelial lymphocytes (IEL) of the colon of IL-2(null) mice were potently cytotoxic ex vivo in short-term redirected cytotoxic lymphocyte (CTL) assays. In contrast, colonic T cells of wild-type animals showed little or no constitutive cytotoxic T cell activity. Colonic CTL were detectable prior to the appearance of disease in IL-2(null) animals and CTL activity was confined to the TcR alpha beta, rather than to the TcR gamma delta TEL subset. IL-2(null) animals crossed with major histocompatibility complex class I-deficient mice [IL-2(null) x beta(2) microglobulin (beta(2)m(null)) mice] also developed colitis, which appeared even earlier than in most IL-2(null) mice. These findings suggest that neither CD8(+) IEL nor LPL were causal in the onset of colitis in IL-2(null) animals. In IL-2(null) x beta(2)m(null) mice, an ulcerative colitis-like disease was evident from histological studies and immunohistological staining which showed very large numbers of CD4(+) lymphocytes within the intestinal mucosa. Significant ex vivo killing by CD4(+) T cells was observed in IL-2(null) x beta(2)m(null) animals, although this required an extended incubation time compared to colonic CD8(+) T cells. Peripheral as well as colonic CD4(+) T cells in IL-2(null) and IL-2(null) x beta(2)m(null) animals, were activated as judged by their cell surface phenotype (CD45RB(lo), L-selectin(lo) and CD69(+)). In light of these findings, we propose that infiltrating CD4(+), but not CD8(+) T cells are central to the inflammation observed in the intestinal mucosa in IL-2(null) colitis. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV IMMUNOL,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. FU NIDDK NIH HHS [P30DK 433-51, R01 DK47677-01] NR 43 TC 117 Z9 122 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 1995 VL 25 IS 9 BP 2618 EP 2625 DI 10.1002/eji.1830250932 PG 8 WC Immunology SC Immunology GA RX342 UT WOS:A1995RX34200031 PM 7589135 ER PT J AU GAUMNITZ, EA BASS, P OSINSKI, MA SWEET, MA SINGARAM, C AF GAUMNITZ, EA BASS, P OSINSKI, MA SWEET, MA SINGARAM, C TI ELECTROPHYSIOLOGICAL AND PHARMACOLOGICAL RESPONSES OF CHRONICALLY DENERVATED LOWER ESOPHAGEAL SPHINCTER OF THE OPOSSUM SO GASTROENTEROLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE; RAT JEJUNUM; ACHALASIA; JUNCTION; TRANSMITTER; MEDIATOR; PRESSURE; NEURONS; INVIVO AB Background and Aims: Achalasia is characterized by loss of myenteric neurons and incomplete relaxation of the lower esophageal sphincter (LES). The aim of this study was to develop an achalasia model in the opossum using the surfactant benzyldimethyltetradecylammonium chloride (BAC). This study further characterizes the achalasia model. Methods: BAC or saline was injected circumferentially into the LES of 14 adult opossums. Eight months after injection, manometry, isolated muscle bath studies, electrical field stimulation, and histochemical analysis were performed. Results: Manometrically, the LES of BAC-treated opossums showed higher pressures (38.7 +/- 12 mm Hg vs. 17 +/- 3.0 mm Hg) and reduced esophageal body contraction amplitudes (4.2 +/- 3 mm Hg vs. 27.4 +/- 12 mm Hg). Isolated muscle strips challenged with carbachol and sodium nitroprusside contracted and relaxed similarly to controls. Electrical field stimulation failed to induce relaxation in BAC-treated tissue but did induce contraction. Contractile responses were markedly reduced by tetrodotoxin and atropine in BAC-treated animals and controls. An altered nitric oxide system was shown by the lack of response to L-arginine and N-omega-nitro-L-arginine. Histology showed loss of myenteric neurons and increased cholinergic nerve bundles. Conclusions: Loss of NO inhibitory myenteric neurons markedly reduces the relaxation of the LES, and histology and pharmacological responses suggest a proliferation of cholinergic nerves into the LES contributing to the static elevated pressures of the amyenteric LES. C1 UNIV WISCONSIN,DEPT MED,DIV GASTROENTEROL,MADISON,WI 53792. UNIV WISCONSIN,SCH PHARM,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. NR 38 TC 21 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1995 VL 109 IS 3 BP 789 EP 799 DI 10.1016/0016-5085(95)90386-0 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RT115 UT WOS:A1995RT11500014 PM 7657107 ER PT J AU FLAHERTY, RF SELTZER, S CAMPBELL, T WEISSKOFF, RM GILBERT, RJ AF FLAHERTY, RF SELTZER, S CAMPBELL, T WEISSKOFF, RM GILBERT, RJ TI DYNAMIC MAGNETIC-RESONANCE-IMAGING OF VOCAL CORD CLOSURE DURING DEGLUTITION SO GASTROENTEROLOGY LA English DT Article ID LARYNX; MECHANISMS; SWALLOW AB Background & Aims: Vocal cord closure is instrumental in airway protection during deglutition. Conventional imaging of vocal cord closure and reopening during deglutition requires invasive and nonphysiological methods. The aim of this study was to characterize the biomechanical properties of normal vocal cord adduction/abduction during deglutition using echoplanar magnetic resonance imaging, a technique that has the capability of imaging soft-tissue motion with real-time temporal resolution. Methods: The movements of laryngeal and vocal cord structures during swallowing were determined in 11 normal volunteers by single slice and axially reformatted multislice coronal echoplanar images. Results: During swallowing, the larynx ascended to peak elevation, maintained peak elevation for a discrete interval, and descended to its resting position. Vocal cord adduction occurred with a symmetric tent-like configuration at the midpoint of maximal laryngeal elevation, whereas vocal cord abduction occurred at the midpoint of laryngeal descent. Spatial analysis of vocal cord configuration during adduction determined that the Vocal cords attained an initial parallel configuration during ascent, followed by closure at peak laryngeal elevation. Conclusions: These results show that the vocal cords adduct and abduct synchronously with laryngeal ascent and descent, respectively, during deglutition. Echoplanar magnetic resonance imaging constitutes a novel tool used to assess clinical abnormalities of deglutitive laryngeal function. C1 ST ELIZABETHS MED CTR,DEPT MED,BOSTON,MA 02135. ST ELIZABETHS MED CTR,DEPT BIOMED RES,BOSTON,MA 02135. TUFTS UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR NUCL MAGNET RESONANCE,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA48729]; NIAID NIH HHS [AI25635] NR 24 TC 23 Z9 23 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1995 VL 109 IS 3 BP 843 EP 849 DI 10.1016/0016-5085(95)90393-3 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RT115 UT WOS:A1995RT11500021 PM 7657113 ER PT J AU RUSTGI, AK AF RUSTGI, AK TI BIOCHEMICAL AND GENETIC SCREENING OF COLORECTAL-CANCER SO GASTROENTEROLOGY LA English DT Editorial Material ID COLONIC EPITHELIAL-CELLS; IDENTIFICATION; MUTATIONS RP RUSTGI, AK (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,GRJ 724,32 FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 1995 VL 109 IS 3 BP 1003 EP 1005 DI 10.1016/0016-5085(95)90414-X PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RT115 UT WOS:A1995RT11500042 PM 7544749 ER PT J AU MAHESWARAN, S ENGLERT, C BENNETT, P HEINRICH, G HABER, DA AF MAHESWARAN, S ENGLERT, C BENNETT, P HEINRICH, G HABER, DA TI THE WT1 GENE-PRODUCT STABILIZES P53 AND INHIBITS P53-MEDIATED APOPTOSIS SO GENES & DEVELOPMENT LA English DT Article DE WT1; WILMS TUMOR; P53; E6; PROTEIN STABILIZATION; APOPTOSIS ID WILMS-TUMOR GENE; HUMAN PAPILLOMAVIRUS TYPE-16; CELL-CYCLE CONTROL; FACTOR-A-CHAIN; DNA-BINDING; E6 ONCOPROTEIN; REPRESSES TRANSCRIPTION; PROMOTER ACTIVITY; SUPPRESSOR GENE; PROTEIN AB The Wilms' tumor-suppressor gene product WT1 coimmunoprecipitates with p53 from baby rat kidney (BRK) cells and Wilms' tumor specimens, and expression of WT1 in BRK cells is associated with increased levels of endogenous wild-type p53 protein. To study the effect of WT1 on p53 function, we cotransfected expression constructs into Saos-2 cells, an osteosarcoma cell line without endogenous expression of either gene. Expression of WT1 resulted in increased steady-state levels of p53, attributable to a prolongation in protein half-life, and associated with protection against papillomavirus Eb-mediated degradation of p53. This effect mapped to zinc fingers 1 and 2 of WT1 and was not observed with the closely related EGR1 protein. The stabilized p53 demonstrated enhanced binding to its target DNA sequence and increased trans-activation of a promoter containing this RGC site, but reduced transcriptional repression of a TATA-containing promoter lacking this site. Expression of WT1 inhibited p53-mediated apoptosis triggered by UV irradiation or by expression of temperature-sensitive p53 in the wild-type conformation, but did not affect p53-mediated cell cycle arrest. We conclude that WT1 protein can stabilize p53, modulate its hans-activational properties, and inhibit its ability to induce apoptosis. This effect may contribute to the elevated levels of wild-type p53 protein that are observed in Wilms' tumors. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. KO TECHNOL,CAMBRIDGE,MA 02139. FU NCI NIH HHS [CA 58596] NR 75 TC 208 Z9 209 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 1 PY 1995 VL 9 IS 17 BP 2143 EP 2156 DI 10.1101/gad.9.17.2143 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA RU602 UT WOS:A1995RU60200006 PM 7657166 ER PT J AU SCHORK, NJ KRIEGER, JE TROLLIET, MR FRANCHINI, KG KOIKE, G KRIEGER, EM LANDER, ES DZAU, VJ JACOB, HJ AF SCHORK, NJ KRIEGER, JE TROLLIET, MR FRANCHINI, KG KOIKE, G KRIEGER, EM LANDER, ES DZAU, VJ JACOB, HJ TI A BIOMETRICAL GENOME SEARCH IN RATS REVEALS THE MULTIGENIC BASIS OF BLOOD-PRESSURE VARIATION SO GENOME RESEARCH LA English DT Article ID SPONTANEOUSLY HYPERTENSIVE RATS; QUANTITATIVE TRAIT LOCI; CONSCIOUS RAT; HEART-RATE; GENE; COSEGREGATION; POLYMORPHISM AB A genome-wide search For multiple loci influencing salt-loaded systolic blood pressure (NaSBP) variation among 188 F-2 progeny from a cross between the Brown-Norway and spontaneously hypertensive rat strains was pursued in an effort to gain insight into the polygenic basis of blood pressure re,oulation. The results suggest that loci within five to six genomic regions collectively explain similar to 43% of the total NaSBP variation exhibited among the 188 F-2 progeny. Many of these loci are in regions that previous studies have not implicated in blood pressure regulation. Ultimately, however, this study not only sheds light on the multigenic basis of blood pressure but provides further evidence that the identification of the genetic determinants of polygenic traits in mammals is possible with modern biometrical and molecular genetic tools in controlled settings (i.e., breeding paradigm and model organism). C1 CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH 44106. JACKSON LAB,BAR HARBOR,ME 04609. UNIV SAO PAULO,SAO PAULO HEART INST,BR-05508 SAO PAULO,BRAZIL. STANFORD UNIV,CARDIOVASC RES CTR,PALO ALTO,CA 94305. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02137. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. RI Krieger, Jose/C-3117-2011; OI Krieger, Jose/0000-0001-5464-1792 FU NHLBI NIH HHS [HL48957-01, HL-46631]; NIDDK NIH HHS [DK47205-01] NR 36 TC 86 Z9 87 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD SEP PY 1995 VL 5 IS 2 BP 164 EP 172 DI 10.1101/gr.5.2.164 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA TD660 UT WOS:A1995TD66000007 PM 9132270 ER PT J AU PETRINI, JHJ WALSH, ME DIMARE, C CHEN, XN KORENBERG, JR WEAVER, DT AF PETRINI, JHJ WALSH, ME DIMARE, C CHEN, XN KORENBERG, JR WEAVER, DT TI ISOLATION AND CHARACTERIZATION OF THE HUMAN MRE11 HOMOLOG SO GENOMICS LA English DT Article ID DNA LIGASE-I; SISTER-CHROMATID EXCHANGES; BLOOMS SYNDROME; SACCHAROMYCES-CEREVISIAE; INSITU HYBRIDIZATION; MEIOTIC RECOMBINATION; MISMATCH REPAIR; WILD-TYPE; GENE; YEAST AB Mutation of the Saccharomyces cerevisiae RAD52 epistasis group gene, MRE11, blocks meiotic recombination, confers profound sensitivity to double-strand break damage, and has a hyperrecombinational phenotype in mitotic cells. We isolated a highly conserved human MRE11 homologue using a two-hybrid screen for DNA Ligase I-interacting proteins. Human MRE11 shares approximately 50% identity with its yeast counterpart over the N-terminal half of the protein. MRE11 is expressed at the highest levels in proliferating tissues, but is also observed in other tissues. The MRE11 locus maps to human chromosome 11q21 in a region frequently associated with cancer-related chromosomal abnormalities. A MRE11-related locus was found on chromosome 7q11.2-q11.3. (C) 1995 Academic Press Inc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,CTR MED GENET BIRTH DEFECTS,AHMANSON DEPT PEDIAT,LOS ANGELES,CA 90048. FU NCI NIH HHS [CA52694]; NHGRI NIH HHS [R29HG00037] NR 60 TC 106 Z9 107 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1995 VL 29 IS 1 BP 80 EP 86 DI 10.1006/geno.1995.1217 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA RU604 UT WOS:A1995RU60400010 PM 8530104 ER PT J AU HUTTER, AM LEIBOVITCH, ER AF HUTTER, AM LEIBOVITCH, ER TI CHEST PAIN - HOW TO DISTINGUISH BETWEEN CARDIAC AND NONCARDIAC CAUSES SO GERIATRICS LA English DT Editorial Material AB Classic coronary pain-or angina-involves a substernal pressure that commonly begins with exertion and is relieved by rest. However, some patients experience angina in the absence of physical exertion or emotional stress, and not all chest pain that begins after exertion is angina. Atypical chest pain must be differentiated fron other types of chest pain, including chest wall pain, pleurisy, gallbladder pain, hiatal hernia, and chest pain associated with anxiety disorders. Careful examination of the chest wall is essential, and abnormal hearts sounds can tell you a great deal. Further testing is individualized. An exercise ECG is important in identifying the presence of ischemic heart disease and the amount of myocardium at risk. If the ECG is abnormal at rest, the patient should undergo a thallium stress test or exercise echocardiography. A coronary angiogram is indicated if the exercise test or an ECG during pain show that a lot of live heart muscle is at risk. C1 MASSACHUSETTS GEN HOSP,MED INTENS CARE COORDINATING COMM,BOSTON,MA 02114. VENTURA CTY MED CTR,VENTURA,CA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. RP HUTTER, AM (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD SEP PY 1995 VL 50 IS 9 BP 32 EP & PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA RV725 UT WOS:A1995RV72500005 PM 7672616 ER PT J AU WILENS, TE SPENCER, TJ BIEDERMAN, J AF WILENS, TE SPENCER, TJ BIEDERMAN, J TI ARE ATTENTION-DEFICIT HYPERACTIVITY DISORDER AND THE PSYCHOACTIVE SUBSTANCE USE DISORDERS REALLY RELATED SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID RISK-FACTORS; PSYCHIATRIC-DISORDERS; CONDUCT DISORDER; COCAINE ABUSERS; ALCOHOL-ABUSE; CHILDHOOD; CHILDREN; FAMILY; COMORBIDITY; BOYS RP WILENS, TE (reprint author), MASSACHUSETTS GEN HOSP, ACC 725, BOSTON, MA 02114 USA. FU PHS HHS [K2001175-02] NR 40 TC 6 Z9 6 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP-OCT PY 1995 VL 3 IS 3 BP 160 EP 162 DI 10.3109/10673229509017182 PG 3 WC Psychiatry SC Psychiatry GA RW336 UT WOS:A1995RW33600006 PM 9384944 ER PT J AU MARRA, F GRANDALIANO, G VALENTE, AJ ABBOUD, HE AF MARRA, F GRANDALIANO, G VALENTE, AJ ABBOUD, HE TI THROMBIN STIMULATES PROLIFERATION OF LIVER FAT-STORING CELLS AND EXPRESSION OF MONOCYTE CHEMOTACTIC PROTEIN-1 - POTENTIAL ROLE IN LIVER-INJURY SO HEPATOLOGY LA English DT Article ID RAT HEPATIC LIPOCYTES; GROWTH-FACTOR; INTRAVASCULAR COAGULATION; CONDITIONED MEDIUM; BLOOD-COAGULATION; MATRIX SYNTHESIS; ALPHA-THROMBIN; ACTIVATION; RECEPTOR; FIBROSIS AB Liver fat-storing cells (FSC) proliferate and secrete extracellular matrix in experimental models of liver injury. In this study, we determined if thrombin, a serine protease produced during acute and chronic tissue injury, modulates the functions of FSC. Thrombin stimulated DNA synthesis and proliferation of FSC, as assessed by [H-3]-thymidine incorporation assay and measurement of cell number, respectively. Thrombin also increased the secretion of monocyte chemotactic protein-1 (MCP-1) in a time- and dose-dependent fashion. The effect of thrombin on both DNA synthesis and MCP-1 secretion was neutralized by pretreatment of thrombin with hirudin. The increased MCP-1 secretion was associated with increased steady-state levels of MCP-1 messenger RNA. Pretreatment of FSC with 5 mu mol/L retinol for 48 hours inhibited the mitogenic effects of thrombin but not the induction of MCP-1 secretion. FSC express specific transcripts encoding for the human thrombin receptor, as shown by Northern blot analysis of poly(A)(+) RNA. Proteolytic activation of the thrombin receptor results in the formation of a new N-terminus that functions as a tethered ligand. We studied the effects of a thrombin receptor activating peptide (TRAP) corresponding to the newly formed N-terminus, on FSC. TRAP mimicked the effects of thrombin on [H-3]thymidine incorporation, MCP-1 secretion, and MCP-1 gene expression. This study suggests that thrombin may be involved in modulating FSC proliferation and monocyte chemotaxis during human liver disease, through proteolytic activation of its receptor. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. RI Grandaliano, Giuseppe/G-2963-2012; Marra, Fabio/K-7263-2016 OI Marra, Fabio/0000-0001-8629-0878 FU NHLBI NIH HHS [HL-26890]; NIDDK NIH HHS [DK-33665, DK-43988] NR 47 TC 89 Z9 91 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 1995 VL 22 IS 3 BP 780 EP 787 DI 10.1016/0270-9139(95)90297-X PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA RT116 UT WOS:A1995RT11600013 PM 7657283 ER PT J AU LEEFLANG, EP ZHANG, L TAVARE, S HUBERT, R SRINIDHI, J MACDONALD, ME MYERS, RH DEYOUNG, M WEXLER, NS GUSELLA, JF ARNHEIM, N AF LEEFLANG, EP ZHANG, L TAVARE, S HUBERT, R SRINIDHI, J MACDONALD, ME MYERS, RH DEYOUNG, M WEXLER, NS GUSELLA, JF ARNHEIM, N TI SINGLE SPERM ANALYSIS OF THE TRINUCLEOTIDE REPEATS IN THE HUNTINGTONS-DISEASE GENE - QUANTIFICATION OF THE MUTATION FREQUENCY-SPECTRUM SO HUMAN MOLECULAR GENETICS LA English DT Article ID AGE-OF-ONSET; COLORECTAL-CANCER; POLYMORPHISM; INSTABILITY; LENGTH; MECHANISM; REGION; LOCUS; DNA AB The CAG triplet repeat region of the Huntington's disease gene was amplified in 923 single sperm from three affected and two normal individuals. Average-size alleles (15-18 repeats) showed only three contraction mutations among 475 sperm (0.6%). A 30 repeat normal allele showed an 11% mutation frequency. The mutation frequency of a 36 repeat intermediate allele was 53% with 8% of all gametes having expansions which brought the allele size into the HD disease range (greater than or equal to 38 repeats). Disease alleles (38-51 repeats) showed a very high mutation frequency (92-99%). As repeat number increased there was a marked elevation in the frequency of expansions, in the mean number of repeats added per expansion and the size of the largest observed expansion. Contraction frequencies also appeared to increase. with allele size but decreased as repeat number exceeded 36. Our sperm typing data are bf a discrete nature rather than consisting of smears of PCR product from pooled sperm. This allowed the observed mutation frequency spectra to be compared to the distribution calculated using discrete stochastic models based on current molecular ideas of the expansion process. An excellent fit was found when the model specified that a random number of repeats are added during the progression of the polymerase through the repeated region. C1 UNIV SO CALIF,PROGRAM MOLEC BIOL,LOS ANGELES,CA 90089. UNIV SO CALIF,DEPT MATH,LOS ANGELES,CA 90089. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. ASSOC FRIENDS FAMILIES HUNTINGTONS DIS,ZULIA,VENEZUELA. COLUMBIA UNIV,DEPT NEUROL,NEW YORK,NY 10032. HEREDITARY DIS FDN,SANTA MONICA,CA 90401. FU NIGMS NIH HHS [R37 GM37645]; NINDS NIH HHS [NS16367, NS22031] NR 38 TC 131 Z9 132 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP PY 1995 VL 4 IS 9 BP 1519 EP 1526 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RT124 UT WOS:A1995RT12400006 PM 8541834 ER PT J AU KOVACS, DM WASCO, W WITHERBY, J FELSENSTEIN, KM BRUNEL, F ROEDER, RG TANZI, RE AF KOVACS, DM WASCO, W WITHERBY, J FELSENSTEIN, KM BRUNEL, F ROEDER, RG TANZI, RE TI THE UPSTREAM STIMULATORY FACTOR FUNCTIONALLY INTERACTS WITH THE ALZHEIMER AMYLOID BETA-PROTEIN PRECURSOR GENE SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRANSCRIPTION FACTOR USF; HELIX-LOOP-HELIX; ISOFORM MESSENGER-RNAS; FACTOR BINDS; ENHANCER BINDING; ACTIVATOR USF; REPORTER GENE; DNA ELEMENTS; PROMOTER; DISEASE AB The amyloid beta-protein precursor (APP) gives rise to the A beta peptide, which is deposited in the brains of patients with Alzheimer's disease and Down's syndrome. Overexpression of APP due to a third copy of the gene appears to correlate with very early onset of Alzheimer's disease neuropathology in the brains of Down's syndrome patients. Thus, the identification of the factors involved with transcriptional regulation of the APP gene could provide critical clues regarding the events leading to the formation of amyloid deposits. An overlapping AP-1/AP-4 site in the proximal promoter region (-39 to -49) of the human APP gene has previously been shown to increase transcription 4-fold. Here we identify the factor binding specifically to this element as the upstream stimulatory factor USF, unrelated to the c-fos/c-jun complex or the AP-4 factor. In vitro transcription and co-transfection studies show that USF activates transcription from the APP promoter and that the AP-1/AP-4 element participates in this activation. Modulation of APP expression via regulation of USF could potentially ameliorate the production of Alzheimer-augmented beta-amyloid. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GENET & AGING UNIT,BOSTON,MA 02129. BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT 06492. ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. FU NCI NIH HHS [CA42567]; NIA NIH HHS [AG11899]; NINDS NIH HHS [NS/AG30428] NR 50 TC 31 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP PY 1995 VL 4 IS 9 BP 1527 EP 1533 DI 10.1093/hmg/4.9.1527 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RT124 UT WOS:A1995RT12400007 PM 8541835 ER PT J AU SERRATOSA, JM DELGADOESCUETA, AV POSADA, I SHIH, S DRURY, I BERCIANO, J ZABALA, JA ANTUNEZ, MC SPARKES, RS AF SERRATOSA, JM DELGADOESCUETA, AV POSADA, I SHIH, S DRURY, I BERCIANO, J ZABALA, JA ANTUNEZ, MC SPARKES, RS TI THE GENE FOR PROGRESSIVE MYOCLONUS EPILEPSY OF THE LAFORA TYPE MAPS TO CHROMOSOME 6Q SO HUMAN MOLECULAR GENETICS LA English DT Article ID LINKAGE ANALYSIS; SKIN BIOPSY; DIAGNOSIS; DISEASE; DNA AB Progressive myoclonus epilepsy of the Lafora type (Lafora's disease) is an autosomal recessive disease characterized by epilepsy, myoclonus, dementia, and periodic acid-Schiff-positive intracellular inclusion bodies. The inclusion deposits consist of branched polysaccharides (polyglucosans) but the responsible biochemical defect has not been identified. Onset is during late childhood or adolescence and the disease leads to a fatal outcome within a decade of first symptoms. We studied nine families in which Lafora's disease had been proven by biopsy in at least one member. In order to locate the responsible gene, we screened the human genome with microsatellite markers spaced an average of 13 cM. We used linkage analysis in all nine families and homozygosity mapping in four consanguineous families to define the Lafora's disease gene region. Two point linkage analysis resulted in a total peak lod score of 10.54 for marker D6S311. Six additional chromosome 6q23-25 microsatellites yielded lod scores ranging from 5.92 to 9.60 at theta(m=f) = 0. An extended pedigree with five affected members independently proved linkage with peak lod scores over 3.8 at theta(m=f) = 0 for D6S292, D6S403, and D6S311. The multipoint one-led-unit support interval covered a 2.5 cM region surrounding D6S403. Homozygosity mapping defined a 17 cM region in chromosome 6q23-25 flanked by D6S292 and D6S420 that contains the Lafora's disease gene. C1 UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. HOSP DOCE OCTUBRE,DEPT NEUROL,E-28041 MADRID,SPAIN. UNIV MICHIGAN HOSP,DEPT NEUROL,ANN ARBOR,MI 48109. UNIV CANTABRIA,HOSP MARQUES VALDECILLA,DEPT NEUROL,E-39008 SANTANDER,SPAIN. CLIN PUERTA HIERRO,NEUROL SERV,E-28035 MADRID,SPAIN. HOSP UNIV VIRGEN ARRIXACA,NEUROL SERV,E-30120 MURCIA,SPAIN. UNIV CALIF LOS ANGELES,DEPT MED,DIV MED GENET,LOS ANGELES,CA 90024. RP SERRATOSA, JM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,CALIF COMPREHENS EPILEPSY PROGRAM,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NINDS NIH HHS [5P01-NS21908] NR 36 TC 93 Z9 93 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP PY 1995 VL 4 IS 9 BP 1657 EP 1663 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA RT124 UT WOS:A1995RT12400029 PM 8541857 ER PT J AU SWERDLOW, SH YANG, WI ZUKERBERG, LR HARRIS, NL ARNOLD, A WILLIAMS, ME AF SWERDLOW, SH YANG, WI ZUKERBERG, LR HARRIS, NL ARNOLD, A WILLIAMS, ME TI EXPRESSION OF CYCLIN D1 PROTEIN IN CENTROCYTIC MANTLE CELL LYMPHOMAS WITH AND WITHOUT REARRANGEMENT OF THE BCL1/CYCLIN D1 GENE SO HUMAN PATHOLOGY LA English DT Article DE CENTROCYTIC LYMPHOMA; MANTLE CELL LYMPHOMA; CYCLIN D1; BCL1/PRAD1 ID CHROMOSOME-11 BCL-1 LOCUS; LYMPHOCYTIC LYMPHOMA; BREAKPOINTS; OVEREXPRESSION; ONCOGENE; G(1) AB Centrocytic/mantle cell lymphoma (CC/MCL) is a morphologically defined B-cell non-Hodgkin's lymphoma characterized by a distinctive immunophenotype, BCLl/cyclin D1 (PRAD1) gene rearrangements, and, most recently, by overexpression of cyclin D1. Even using multiple breakpoint probes for BCL1 (MTC, p94PS) and cyclin D1, however, only approximately 70% of CC/MCL have a rearrangement consistent with a t(11;14) (q13;q32). To determine whether the type of molecular translocation affects the degree of cyclin DI expression and to evaluate lymphomas diagnosed as CC/MCL but lacking molecular evidence of a BCL1 or cyclin D1 translocation, 16 CC/MCL and four cases of small lymphocytic lymphoma/BCL1 (SLL/B-CLL) were stained using an anti-cyclin D1 antibody. All cases with a cyclin DI translocation detected by Southern blotting techniques as well as four of the five CC/MCL without a documentable translocation showed nuclear cyclin D1 protein expression. There was no apparent correlation between staining intensity and the precise site or presence of a detectable translocation. Cases with a mantle zone growth pattern showed infiltration of the cyclin D1 positive cells into reactive follicular centers. None of the four SLL/B-CLL showed cyclin D1 expression. These findings show overexpression of the cyclin D1 protein in virtually all CC/MCL independent of the type or presence of a documentable BCL1 or cyclin D1 molecular rearrangement. The mechanism for cyclin D1 overexpression in the cases without a documentable rearrangement and the relationship of cyclin D1 overexpression to the pathogenesis of mantle cell neoplasia remain uncertain. Copyright (C) 1995 by W.B. Saunders Company C1 UNIV PITTSBURGH,SCH MED,DEPT PATHOL,PITTSBURGH,PA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE ONCOL UNIT,BOSTON,MA. UNIV VIRGINIA,SCH MED,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,SCH MED,DEPT PATHOL,CHARLOTTESVILLE,VA 22908. FU PHS HHS [P30-44579] NR 37 TC 83 Z9 83 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1995 VL 26 IS 9 BP 999 EP 1004 DI 10.1016/0046-8177(95)90090-X PG 6 WC Pathology SC Pathology GA RT729 UT WOS:A1995RT72900012 PM 7545645 ER PT J AU SIMON, JS ROMAN, RJ COWLEY, AW GREENE, A JACOB, HJ AF SIMON, JS ROMAN, RJ COWLEY, AW GREENE, A JACOB, HJ TI RAT ALPHA-2-ADRENERGIC RECEPTOR CLASS-III IS LINKED TO SYSTOLIC BLOOD-PRESSURE AFTER SALT-LOAD IN GENETIC-HYPERTENSION SO HYPERTENSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. MED COLL WISCONSIN,MILWAUKEE,WI 53226. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1995 VL 26 IS 3 BP 537 EP 537 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RU148 UT WOS:A1995RU14800030 ER PT J AU TROLLIET, MR KRIEGER, JE KOIKE, G SIMON, J KRIEGER, EM DZAU, V JACOB, HJ AF TROLLIET, MR KRIEGER, JE KOIKE, G SIMON, J KRIEGER, EM DZAU, V JACOB, HJ TI GENDER AND GRANDPARENTAL STRAIN INFLUENCES THE GENETIC-BASIS OF BLOOD-PRESSURE (BP) SO HYPERTENSION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,ICVRC,BOSTON,MA. UNIV SAO PAULO,INST HEART,BR-05508 SAO PAULO,BRAZIL. STANFORD UNIV,CVRC,STANFORD,CA. RI Krieger, Jose/C-3117-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1995 VL 26 IS 3 BP 537 EP 537 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA RU148 UT WOS:A1995RU14800031 ER PT J AU ROGOWSKA, J PRESTON, K HUNTER, GJ HAMBERG, LM KWONG, KK SALONEN, O WOLF, GL AF ROGOWSKA, J PRESTON, K HUNTER, GJ HAMBERG, LM KWONG, KK SALONEN, O WOLF, GL TI APPLICATIONS OF SIMILARITY MAPPING IN DYNAMIC MRI SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article AB Dynamic images are temporal sequences of images, where the intensities of certain regions of interest (ROI's) change with time, whereas anatomical structures remain stationary, In this paper, new applications of dynamic image analysis, called similarity mapping, are reviewed. Similarity mapping identifies regions in a dynamic image sequence according to their temporal similarity or dissimilarity with respect to a reference ROI. Pixels in the resulting similarity map whose temporal sequence is similar to the reference ROI have high correlation values and are bright, while those with low correlation values are dark, Therefore, similarity mapping segments structures in a dynamic image sequence based on their temporal responses rather than spatial properties, This paper describes the abilities of similarity mapping to identify different image structures present in several dynamic MRI datasets with potential clinical value. We demonstrate that similarity mapping technique has been successful in identifying the following structures: 1) renal cortex and medulla, 2) activated areas of the brain during photic stimulation, 3) ischemia in the left coronary artery territory, 4) lung tumor, 5) tentorial meningioma, and 6) a region of focal ischemia in brain. C1 CARNEGIE MELLON UNIV,DEPT ELECT & COMP ENGN,PITTSBURGH,PA 15213. MASSACHUSETTS GEN HOSP,CTR NMR,DEPT RADIOL,BOSTON,MA 02129. UNIV HELSINKI,CENT HOSP,DEPT RADIOL,HELSINKI,FINLAND. RP ROGOWSKA, J (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR IMAGING & PHARMACEUT RES,DEPT RADIOL,BOSTON,MA 02129, USA. NR 17 TC 24 Z9 24 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD SEP PY 1995 VL 14 IS 3 BP 480 EP 486 DI 10.1109/42.414613 PG 7 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA RU692 UT WOS:A1995RU69200008 PM 18215852 ER PT J AU KHAN, WN ALT, FW GERSTEIN, RM MALYNN, BA LARSSON, I RATHBUN, G DAVIDSON, L MULLER, S KANTOR, AB HERZENBERG, LA ROSEN, FS SIDERAS, P AF KHAN, WN ALT, FW GERSTEIN, RM MALYNN, BA LARSSON, I RATHBUN, G DAVIDSON, L MULLER, S KANTOR, AB HERZENBERG, LA ROSEN, FS SIDERAS, P TI DEFECTIVE B-CELL DEVELOPMENT AND FUNCTION IN BTK-DEFICIENT MICE SO IMMUNITY LA English DT Review ID X-LINKED AGAMMAGLOBULINEMIA; CBA-N MICE; PROTEIN-TYROSINE KINASES; HEAT-STABLE ANTIGEN(HI); BONE-MARROW CELLS; PRE-B; LYMPHOCYTES-B; LIGHT-CHAIN; SRC FAMILY; SIGNALING PROTEINS AB Mutations in the Bruton's tyrosine kinase (Btk) gene have been linked to severe early B cell developmental blocks in human X-linked agammaglobulinemia (XLA), and to milder B cell activation deficiencies in murine X-linked immune deficiency (Xid). To elucidate unequivocally potential Btk functions in mice, we generated mutations in embryonic stem cells, which eliminated the ability to encode Btk pleckstrin homology or kinase domains, and assayed their effects by RAG2-deficient blastocyst complementation or introduction into the germline. Both mutations block expression of Btk protein and lead to reduced numbers of mature conventional B cells, severe B1 cell deficiency, serum IgM and lgG3 deficiency, and defective responses in vitro to various B cell activators and in vivo to immunization with thymus-independent type II antigens. These results prove that lack of Btk function results in an Xid phenotype and further suggest a differential requirement for Btk during the early stages of murine versus human B lymphocyte development. C1 CTR BLOOD RES,BOSTON,MA 02115. STANFORD UNIV,MED CTR,BECKMAN CTR,DEPT GENET,STANFORD,CA 94305. UMEA UNIV,APPL CELL & MOLEC BIOL UNIT,S-90187 UMEA,SWEDEN. RP KHAN, WN (reprint author), CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI20047, AI34762, P01AI35714] NR 100 TC 523 Z9 528 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 50 CHURCH ST CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 1995 VL 3 IS 3 BP 283 EP 299 DI 10.1016/1074-7613(95)90114-0 PG 17 WC Immunology SC Immunology GA RX645 UT WOS:A1995RX64500004 PM 7552994 ER PT J AU GIRARD, JP SPRINGER, TA AF GIRARD, JP SPRINGER, TA TI HIGH ENDOTHELIAL VENULES (HEVS) - SPECIALIZED ENDOTHELIUM FOR LYMPHOCYTE MIGRATION SO IMMUNOLOGY TODAY LA English DT Review ID BLOOD-BRAIN-BARRIER; VASCULAR ADDRESSIN EXPRESSION; TISSUE-SPECIFIC MIGRATION; NONOBESE DIABETIC MICE; L-SELECTIN; RECIRCULATING LYMPHOCYTES; LEUKOCYTE EXTRAVASATION; MOLECULAR MECHANISMS; EXTRACELLULAR-MATRIX; FUNCTIONAL-ACTIVITY AB High endothelial venules (HEVs) are specialized postcapillary venules found in lymphoid tissues that support high levels of lymphocyte extra-vasation from the blood. Here, Jean-Philippe Girard and Timothy Springer highlight the unique properties of HEV endothelium, discuss the molecular mechanisms controlling HEV specialization and review evidence suggesting that HEVs could play an important role in the pathogenesis of chronic inflammatory diseases. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP GIRARD, JP (reprint author), CNRS,BIOL MOLEC EUCARYOTE LAB,118 ROUTE NARBONNE,F-31062 TOULOUSE,FRANCE. RI GIRARD, Jean-Philippe/F-5229-2010 FU NCI NIH HHS [CA 31798] NR 83 TC 370 Z9 377 U1 1 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD SEP PY 1995 VL 16 IS 9 BP 449 EP 457 DI 10.1016/0167-5699(95)80023-9 PG 9 WC Immunology SC Immunology GA RR843 UT WOS:A1995RR84300009 PM 7546210 ER PT J AU FRAIMOW, HS ABRUTYN, E AF FRAIMOW, HS ABRUTYN, E TI PATHOGENS RESISTANT TO ANTIMICROBIAL AGENTS - EPIDEMIOLOGY, MOLECULAR MECHANISMS, AND CLINICAL MANAGEMENT SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID SPECTRUM BETA-LACTAMASES; HIGH-LEVEL RESISTANCE; PENICILLIN-BINDING PROTEINS; STAPHYLOCOCCUS-AUREUS; ENTEROCOCCUS-FAECIUM; STREPTOCOCCUS-PNEUMONIAE; PNEUMOCOCCAL MENINGITIS; VANCOMYCIN-RESISTANT; ESCHERICHIA-COLI; HAEMOPHILUS-INFLUENZAE AB Over the last decade, an ominous trend in the field of antimicrobial chemotherapy has been the increasing pace of the development of antimicrobial resistance in bacterial pathogens. This article reviews the strategies used by bacteria to avoid the action of antimicrobial agents and how these resistance traits are disseminated. Resistance among the common community and nosocomially acquired pathogens, and the current approach to therapy of these organisms are discussed in this article. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. GRAD HOSP PHILADELPHIA,PHILADELPHIA,PA 19104. MED COLL PENN,PHILADELPHIA,PA 19104. HAHNEMANN UNIV,PHILADELPHIA,PA 19104. NR 113 TC 31 Z9 31 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 1995 VL 9 IS 3 BP 497 EP & PG 0 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RV007 UT WOS:A1995RV00700004 PM 7490430 ER PT J AU KAYE, ET KAYE, KM AF KAYE, ET KAYE, KM TI TOPICAL ANTIBACTERIAL AGENTS SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID ORAL ERYTHROMYCIN; STAPHYLOCOCCUS-AUREUS; MUPIROCIN TREATMENT; VENOUS CATHETERS; POVIDONE-IODINE; CLINICAL-TRIAL; SKIN; PREVENTION; IMPETIGO; OINTMENT AB Topical antibacterial agents play a unique role in antimicrobial therapy. Advantages of topical over systemic therapy include a decreased risk of systemic toxicity, higher concentration at the target site, less opportunity for the development of resistance in gastrointestinal flora, and convenience of application. This article reviews indications for the use of topical antimicrobials for both the prophylaxis and treatment of skin and wound infections. Specific agents are also reviewed. C1 BRIGHAM & WOMENS HOSP,DIV INFECT DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 62 TC 7 Z9 7 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 1995 VL 9 IS 3 BP 547 EP & PG 0 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RV007 UT WOS:A1995RV00700006 PM 7490432 ER PT J AU BUSH, LM CALMON, J JOHNSON, CC AF BUSH, LM CALMON, J JOHNSON, CC TI NEWER PENICILLINS AND BETA-LACTAMASE INHIBITORS SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID PLUS CLAVULANIC ACID; GRANULOCYTOPENIC CANCER-PATIENTS; BACTEROIDES-FRAGILIS GROUP; PIPERACILLIN-TAZOBACTAM; PSEUDOMONAS-AERUGINOSA; BINDING PROTEINS; INVITRO ACTIVITY; ESCHERICHIA-COLI; AMPICILLIN-SULBACTAM; ANAEROBIC-BACTERIA AB Penicillins continue to be essential antibiotics for the treatment and prophylaxis of many infectious diseases. Recent advances have resulted in compounds with favorable new antimicrobial and pharmacologic properties. This article reviews the spectrum of activity, toxicity, pharmacokinetics, and clinical uses of the extended spectrum penicillins and the beta-lactamase inhibitor combination agents. C1 MED COLL PENN,DIV INFECT DIS,PHILADELPHIA,PA 19129. HAHNEMANN UNIV,SCH MED,PHILADELPHIA,PA 19129. JFK MED CTR,W PALM BEACH,FL. CROZER CHESTER MED CTR,CHESTER,PA. VET AFFAIRS MED CTR,PHILADELPHIA,PA. NR 154 TC 13 Z9 13 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 1995 VL 9 IS 3 BP 653 EP & PG 0 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RV007 UT WOS:A1995RV00700012 PM 7490438 ER PT J AU SHEPARD, DS STASON, WB PERRY, HM CARMEN, BA NAGURNEY, JT AF SHEPARD, DS STASON, WB PERRY, HM CARMEN, BA NAGURNEY, JT TI MULTIVARIATE COST-EFFECTIVENESS ANALYSIS - AN APPLICATION TO OPTIMIZING AMBULATORY CARE FOR HYPERTENSION SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING LA English DT Article AB Cost-effectiveness analysis (CEA) is being used increasingly to allocate health resources efficiently. This paper develops an extension of CEA based on multivariate regression analysis and applies if to hypertension treatment. After assembling clinic and patient characteristics, outcomes, and costs for 2,439 randomly chosen patients in the 32 special hypertension clinics of the Department of Veterans Affairs (VA), we identified 19 significant predictors of cost and diastolic blood pressure (DBP) using multiple regression analysis. We classified these independent variables as ''unambiguous'' if a given change was associated with both lower cost and better DBP, or as ''trade-off'' variables if any change improving DBP entailed higher costs. The results suggest that fully implementing all unambiguous clinic changes would reduce costs by 33% while improving DBP. Multivariate CEA could help managed care companies and government programs with cost and outcome data to reduce costs and improve outcomes. C1 HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. VET ADM MED CTR,DEPT MED,HYPERTENS SECT,ST LOUIS,MO 63125. MASSACHUSETTS GEN HOSP,DEPT EMERGENCY MED,BOSTON,MA 02114. RP SHEPARD, DS (reprint author), BRANDEIS UNIV,HELLER SCH,INST HLTH POLICY,415 S ST,WALTHAM,MA 02254, USA. FU NIDA NIH HHS [DA 08739-02] NR 13 TC 11 Z9 11 U1 0 U2 1 PU BLUE CROSS BLUE SHIELD ASSN PI CHICAGO PA 676 N ST CLAIR ST, CHICAGO, IL 60611 SN 0046-9580 J9 INQUIRY-J HEALTH CAR JI Inquiry-J. Health Care Organ. Provis. Financ. PD FAL PY 1995 VL 32 IS 3 BP 320 EP 331 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA TA494 UT WOS:A1995TA49400010 PM 7591045 ER PT J AU TEICHER, BA HOLDEN, SA ARA, G MENON, K AF TEICHER, BA HOLDEN, SA ARA, G MENON, K TI WHOLE-BODY HYPERTHERMIA AND LONIDAMINE AS ADJUVANT THERAPY TO TREATMENT WITH CISPLATIN WITH OR WITHOUT LOCAL RADIATION IN MOUSE BEARING THE LEWIS LUNG-CARCINOMA SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE WHOLE-BODY HYPERTHERMIA; LONIDAMINE; LUNG METASTASES; CIS-DIAMMINEDICHLOROPLATINUM (II) ID ASCITES TUMOR-CELLS; CIS-DIAMMINEDICHLOROPLATINUM; ALKYLATING-AGENTS; FSAIIC FIBROSARCOMA; CANCER-PATIENTS; FIBRO-SARCOMA; RENAL INJURY; FLUOSOL-DA; MURINE; INVITRO AB The Lewis lung carcinoma implanted subcutaneously in the hind leg of a C57BL mouse metastasizes avidly to the lungs of the host. This tumour model system thus allows assessment of both primary and metastatic disease to treatment. Lonidamine (50 mg/kg) administered once or twice daily produced approximately additive tumour growth delay with whole-body hyperthermia (60 min to 42 degrees C and 60 min at 42 degrees C). The addition of lonidamine to treatment with cisplatin (10 mg/kg) and whole-body hyperthermia continued to produce increased tumour growth delay of up to 14.7 days compared with 10-8 days for cisplatin/whole-body hyperthermia. The response of the metastatic disease paralleled that of the primary tumour with a reduction in the number and percent of large metastases ( > 3 mm) on day 20 post-tumour implantation. The addition of local fractionated radiation therapy (3 Gy x 5) to the primary tumour produced a very effective treatment regimen resulting in 37.5 days of tumour growth delay along with twice daily lonidamine/cisplatin whole-body hyperthermia. With this treatment regimen there was also a reduction to 50% of control of the number of lung metastases as well as the percent of large metastases on day 20. Further investigation of these treatment combinations is warranted. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP TEICHER, BA (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [R01-CA50174, P01-CA31303] NR 49 TC 6 Z9 6 U1 1 U2 1 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD SEP-OCT PY 1995 VL 11 IS 5 BP 637 EP 645 DI 10.3109/02656739509022496 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA RM988 UT WOS:A1995RM98800004 PM 7594815 ER PT J AU BLUMENTHAL, D AF BLUMENTHAL, D TI RADICAL SURGERY - WHATS NEXT FOR AMERICA HEALTH-CARE - CALIFANO,JA SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Book Review C1 MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114. RP BLUMENTHAL, D (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD FAL PY 1995 VL 12 IS 1 BP 85 EP 88 PG 4 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA TB409 UT WOS:A1995TB40900034 ER PT J AU KRAUS, BB ROS, PR ABBITT, PL KERNS, SR SABATELLI, FW AF KRAUS, BB ROS, PR ABBITT, PL KERNS, SR SABATELLI, FW TI COMPARISON OF ULTRASOUND, CT, AND MR-IMAGING IN THE EVALUATION OF CANDIDATES FOR TIPS SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE TIPS; MRI; LIVER; PORTAL VEIN AB To compare ultrasound (US), CT, and MRI in the evaluation of hepatic vascular anatomy, portal and splenic venous flow, and collateral pathways (varices and spontaneous shunts) in candidates for transjugular intrahepatic portosystemic shunting (TIPS), 17 patients with history of refractory variceal bleeding or intractable ascites underwent duplex US, contrast-enhanced CT, and MRI before TIPS, The appearance of portal and hepatic anatomy was graded from 1 (not visible) to 4 (excellent visualization) independently by four radiologists, Presence and direction of portal and splenic venous now, and presence and location of varices and spontaneous portosystemic shunts were also assessed, Results and effects of interobserver variation were assessed for significance using Friedman's ANOVA and Wilcoxon's signed-rank test, MRI yielded higher scores than CT or US for hepatic veins (P<.0001) and inferior vena cava (P<.0001), MRI and CT scored better than US for portal vein branches (P=.012) and splenic vein (P=.0038), All tests demonstrated the main portal vein well, with no statistically significant difference, US and MRI were more sensitive than CT for detecting portal vein flow and direction (US 76%, CT 0%, MRI 82%), MRI was most sensitive for splenic vein flow and direction (US 41%, CT 0%, MRI 76%), CT and MRI were more sensitive than US in detecting varices (US 5%, CT 50%, MRI 58%) and spontaneous shunts (US 13%, CT 75%, MRI 75%), Interobserver variation did not influence results significantly P=.3691), MRI provides the most useful information and may be the preferred single imaging test prior to TIPS. RP KRAUS, BB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,WACC 515,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 0 TC 10 Z9 11 U1 0 U2 0 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD SEP-OCT PY 1995 VL 5 IS 5 BP 571 EP 578 DI 10.1002/jmri.1880050517 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA RX131 UT WOS:A1995RX13100015 PM 8574044 ER PT J AU CHECROUNE, F YAO, XJ GOTTLINGER, HG BERGERON, D COHEN, EA AF CHECROUNE, F YAO, XJ GOTTLINGER, HG BERGERON, D COHEN, EA TI INCORPORATION OF VPR INTO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 - ROLE OF CONSERVED REGIONS WITHIN THE P6 DOMAIN OF PR55(GAG) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE VPR; PACKAGING; HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 ID FUNCTIONAL-ANALYSIS; PROTEIN; HIV-1; GAG; EXPRESSION; VIRIONS; REV; PARTICLES; RELEASE; PR55GAG AB The 96-amino acid Vpr protein is the only virion-associated regulatory protein encoded by the human immunodeficiency virus type 1 (HIV-1). Vpr incorporation into the viral particle is most likely due to an interaction with a viral structural protein. Recent data have shown that DNA encoding for the p55 Gag precursor protein (pr55(gag)) is minimal viral genetic information necessary for Vpr incorporation. Other studies have suggested that the p6 portion of pr55(gag), which is unique to lentiviruses, is involved in Vpr incorporation. To investigate the mechanism of incorporation of Vpr into HIV-1 virions, COS-7 cells were cotransfected with ptrENV, an expression vector that encodes all of the HIV-1 regulatory proteins including Rev and Vpr, and different constructs of pIIIgagCAR, a rev-dependent Gag expression plasmid that encodes Pr55(gag) and the viral protease. Virions produced from gag constructs containing a premature p6 termination codon at positions Leu-1, Ser-17, Tyr-36, or Leu-44 lacked detectable Vpr. In contrast, gag constructs with double Pro-10-Pro-11 substitutions for Leu-10-Leu-11 or a premature termination codon at position Pro-49 of p6 were still able to incorporate Vpr, however, with lower efficiency than wild type. The mutations described in this study affected directly two short regions within the p6 domain, which are highly conserved among primate immunodeficiency viruses. Our results suggest that the conserved (P-T/S-A-P-P) and (L-X-S-L-F-G) motifs located near the N-terminus and C-terminus, respectively, of the p6 domain of Gag are critical for Vpr incorporation into HIV-1 virions. C1 UNIV MONTREAL,FAC MED,DEPT MICROBIOL & IMMUNOL,RETROVIROL HUMAINE LAB,MONTREAL,PQ H3C 3J7,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 23 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD SEP 1 PY 1995 VL 10 IS 1 BP 1 EP 7 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA RR296 UT WOS:A1995RR29600001 PM 7648278 ER PT J AU DAVIES, JP HARRIS, WH AF DAVIES, JP HARRIS, WH TI COMPARISON OF DIAMETRAL SHRINKAGE OF CENTRIFUGED AND UNCENTRIFUGED SIMPLEX P(R) BONE-CEMENT SO JOURNAL OF APPLIED BIOMATERIALS LA English DT Article AB Reducing the porosity of bone cement substantially strengthens the cement in fatigue, However, concern has been raised that reducing the porosity of the cement would increase the shrinkage of the cement and thus compromise the cement-bone interface. We measured diametral shrinkage of cement mantles prepared with and without centrifugation of the cement, Four cement preparations (centrifuged and uncentrifuged mixed with monomer at either room temperature or O degrees C) were used to form cement mantles of four different thicknesses (2, 4, 6, and 8 mm) around a stainless steel rod, We conclude that porosity reduction dramatically increases the fatigue strength of bone cement without substantially changing the diametral dimensions of the polymerized cement when studied in the shape and volume of a cement mantle that would be used for total hip replacement. (C) 1995 John Wiley and Sons, Inc. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 6 TC 15 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-4861 J9 J APPL BIOMATER JI J. Appl. Biomater. PD FAL PY 1995 VL 6 IS 3 BP 209 EP 211 DI 10.1002/jab.770060311 PG 3 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA RP054 UT WOS:A1995RP05400010 PM 7492813 ER PT J AU GUNN, JS ALPUCHEARANDA, CM LOOMIS, WP BELDEN, WJ MILLER, SI AF GUNN, JS ALPUCHEARANDA, CM LOOMIS, WP BELDEN, WJ MILLER, SI TI CHARACTERIZATION OF THE SALMONELLA-TYPHIMURIUM PAGC/PAGD CHROMOSOMAL REGION SO JOURNAL OF BACTERIOLOGY LA English DT Article ID VIBRIO-CHOLERAE; VIRULENCE DETERMINANTS; ESCHERICHIA-COLI; YERSINIA-ENTEROCOLITICA; DIVERGENT PROMOTERS; GENETIC-ANALYSIS; PHOP-PHOQ; INVASION; PHOSPHATASE; MACROPHAGE AB The PhoP/PhoQ two-component system regulates Salmonella typhimurium genes that are essential to bacterial virulence and survival within macrophages. The best characterized of these PhoP-activated genes (pag) is pagC, which encodes a 188-amino-acid envelope protein (W. S. Pulkkinen and S. L. Miller, J. Bacteriol. 173:86-93, 1991). We here report the identification of four genes (pagD, envE, msgA, and envF) located 5' to pagC. Each gene is transcribed from its own promoter, two of which (msgA and pagD) were defined by primer extension analysis. Three of these genes (pagD, envE, and envF) are predicted to encode envelope proteins. The pagD gene is transcribed in a direction opposite from that of and adjacent to pagC and is positively regulated by PhoP/PhoQ. Transposon insertions within pagD and msgA attenuate bacterial virulence and survival within macrophages; however, deletion of pagD has no effect on virulence. The product of the envF gene is predicted to be a lipoprotein on the basis of the presence of a consensus lipid attachment site. The low G+C content of these genes and the homology of msgA to Shigella plasmid DNA suggest that this region may have been acquired by horizontal transmission. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RI Gunn, John/E-3167-2011 FU NIAID NIH HHS [AI07061-16, AI30479] NR 48 TC 66 Z9 71 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 1995 VL 177 IS 17 BP 5040 EP 5047 PG 8 WC Microbiology SC Microbiology GA RR981 UT WOS:A1995RR98100029 PM 7665482 ER PT J AU PARK, JC YASEEN, NR HOGAN, PG RAO, A SHARMA, S AF PARK, JC YASEEN, NR HOGAN, PG RAO, A SHARMA, S TI PHOSPHORYLATION OF THE TRANSCRIPTION FACTOR NFATP INHIBITS ITS DNA-BINDING ACTIVITY IN CYCLOSPORINE-A-TREATED HUMAN B-CELLS AND T-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR FACTOR; INTERLEUKIN-2 PROMOTER; ANTIGEN RECEPTOR; LYMPHOCYTE; IDENTIFICATION; ACTIVATION; CALCINEURIN; GENE; ENHANCER; COMPLEX AB Cyclosporin A (CsA) exerts its immunosuppressive effect by inhibiting the activity of nuclear factor of activated T cells (NFAT), thus preventing transcriptional induction of several cytokine genes. This effect is thought to be largely mediated through inactivation of the phosphatase calcineurin, which in turn inhibits translocation of an NFAT component to the nucleus. Here we report that CsA treatment of Raji B and Jurkat T cell lines yields a phosphorylated form of NFATp that is inhibited in DNA-binding and in its ability to form an NFAT complex with Fos and Jun. Immunoblot analyses and metabolic labeling with [P-32]orthophosphate show that CsA alters NFATp migration on SDS-polyacrylamide gel electrophoresis by increasing its phosphorylation level without affecting subcellular distribution. Dephosphorylation by in vitro treatment with calcineurin or alkaline phosphatase restores NFATp DNA binding activity and its ability to reconstitute an NFAT complex with Fos and Jun proteins. These data point to a new mechanism for CsA-sensitive regulation of NFATp in which dephosphorylation is critical for DNA binding. C1 BROWN UNIV,ROGERS WILLIAMS MED CTR,DEPT PATHOL,EXPTL PATHOL SECT,PROVIDENCE,RI 02908. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA42471, CA55910]; NIGMS NIH HHS [GM46227] NR 42 TC 77 Z9 78 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 1995 VL 270 IS 35 BP 20653 EP 20659 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR584 UT WOS:A1995RR58400064 PM 7657645 ER PT J AU JUNG, JU LANG, SM FRIEDRICH, U JUN, T ROBERTS, TM DESROSIERS, RC BIESINGER, B AF JUNG, JU LANG, SM FRIEDRICH, U JUN, T ROBERTS, TM DESROSIERS, RC BIESINGER, B TI IDENTIFICATION OF LCK-BINDING ELEMENTS IN TIP OF HERPESVIRUS SAIMIRI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASES; CELL ANTIGEN RECEPTOR; SH3 DOMAINS; SIGNAL TRANSDUCTION; PHOSPHOENOLPYRUVATE CARBOXYLASE; INVITRO IMMORTALIZATION; LYMPHOCYTES-T; ACTIVATION; P56LCK; EXPRESSION AB A protein called Tip (tyrosine kinase interacting protein) of herpesvirus saimiri associates with Lck in virus-transformed human T cells and is an in vitro substrate for Lck kinase. Mutational analyses of a GST-Tip fusion protein revealed that binding to Lck requires putative SH3 binding sequences and a sequence homologous to the carboxyl terminus of Src-related kinases. These sequences are referred to as SH3-Binding (SH3B) and C-terminal Src-related Kinase Homology (CSKH) elements. Peptide fragments as short as 37 amino acids containing both SH3B and CSKH elements were sufficient to form a stable complex with Lck in vitro. Furthermore, these same sequences of Tip were necessary for in vivo association with Lck when Tip and Lck were expressed transiently in COS-1 cells or stably in Rat-1 cell lines. These results demonstrate that the CSKH element of Tip participates in the binding of sequences within Lck. Tip of herpesvirus saimiri has apparently acquired such CSKH and SH3B elements for the purpose of targeting cellular protein kinases. The interaction of Tip with Lck may influence Lck kinase activity or its binding to other cellular proteins and thereby alter Lck function in T cells infected by h. saimiri. C1 UNIV ERLANGEN NURNBERG,INST KLIN & MOLEK VIROL,D-91054 ERLANGEN,GERMANY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT CELLULAR & MOLEC BIOL,BOSTON,MA 02115. RP JUNG, JU (reprint author), HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DEPT MICROBIOL & MOLEC GENET,SOUTHBOROUGH,MA 01772, USA. FU NCI NIH HHS [CA31363]; NCRR NIH HHS [RR00168] NR 54 TC 81 Z9 84 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 1995 VL 270 IS 35 BP 20660 EP 20667 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA RR584 UT WOS:A1995RR58400065 PM 7544793 ER PT J AU PFLEIDERER, B XU, P ACKERMAN, JL GARRIDO, L AF PFLEIDERER, B XU, P ACKERMAN, JL GARRIDO, L TI STUDY OF AGING OF SILICONE-RUBBER BIOMATERIALS WITH NMR SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID SI-29 NMR; NETWORKS; MODEL; POLYDIMETHYLSILOXANE; IMPLANTS AB Multinuclear nuclear magnetic resonance (NMR) spectroscopy (Si-29, C-13, H-1) is used to characterize the aging process of silicone rubber-based biomaterials in a rat model. H-1 NMR relaxation measurements (spin-lattice, T-1, and spin-spin, T-2, relaxation times) were performed to better understand the molecular dynamics of polysiloxane chains in implants. After 1 year of implantation in animals, changes in the H-1 T-2 relaxation times and the NMR spectra were observed in polydimethylsiloxane, Silastic(R) sheets and chin implants, while these measurements remain unchanged in finger joints. Very small amounts of fat were detected in all types of silicone rubber implants at the end of the implantation period. This work shows that free silicone migrates from the implants to adjacent tissues and distant sites, such as spleen or liver, and is chemically modified. (C) 1995 John Wiley and Sons, Inc. C1 MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,BIOMAT LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV CINCINNATI,DEPT CHEM,CINCINNATI,OH 45221. RI Garrido, Leoncio/K-3092-2014; Ackerman, Jerome/E-2646-2015 OI Garrido, Leoncio/0000-0002-7587-1260; Ackerman, Jerome/0000-0001-5176-7496 NR 36 TC 20 Z9 21 U1 0 U2 7 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD SEP PY 1995 VL 29 IS 9 BP 1129 EP 1140 DI 10.1002/jbm.820290913 PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA RR477 UT WOS:A1995RR47700012 PM 8567711 ER PT J AU MODABBER, R JUPITER, JB AF MODABBER, R JUPITER, JB TI RECONSTRUCTION FOR POSTTRAUMATIC CONDITIONS OF THE ELBOW JOINT SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID HETEROTOPIC OSSIFICATION; FLEXION CONTRACTURES; HINGE-DISTRACTOR; ECTOPIC BONE; ULNAR NERVE; ARTHROPLASTY; DISLOCATION; REPLACEMENT; MOTION; ARTHROLYSIS C1 MASSACHUSETTS GEN HOSP,ORTHOPAED HAND SERV,BOSTON,MA 02114. RP MODABBER, R (reprint author), TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,DEPT ORTHOPAED SURG,750 WASHINGTON ST,BOSTON,MA 02111, USA. NR 215 TC 22 Z9 24 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. vol. PD SEP PY 1995 VL 77 IS 9 BP 1431 EP 1446 PG 16 WC Orthopedics; Surgery SC Orthopedics; Surgery GA RV568 UT WOS:A1995RV56800021 PM 7673296 ER PT J AU CORBETT, AH KOEPP, DM SCHLENSTEDT, G LEE, MS HOPPER, AK SILVER, PA AF CORBETT, AH KOEPP, DM SCHLENSTEDT, G LEE, MS HOPPER, AK SILVER, PA TI RNA1P, A RAN/TC4 GTPASE-ACTIVATING PROTEIN, IS REQUIRED FOR NUCLEAR IMPORT SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CHROMOSOME CONDENSATION; BINDING PROTEINS; MESSENGER-RNA; YEAST MUTANT; PORE COMPLEX; GENE-PRODUCT; RCC1; REGULATOR; LOCALIZATION AB The Saccharomyces cerevisiae gene, RNA1, encodes a protein with extensive homology to the mammalian Ran/TC4 GTPase activating protein, Using indirect immunofluorescence microscopy, we have demonstrated that rna1-1 mutant cells are defective in nuclear import of several proteins. The same result is obtained when nuclear import is examined in living cells using a nuclear protein fused to the naturally green fluorescent protein. These findings suggest a role for the Rna1p in trafficking of proteins across the nuclear membrane. To investigate this role more directly, an in vitro import assay that monitors the import of a fluorescently labeled substrate into the nuclei of semi-intact yeast cells was used. Import to the nucleus requires the addition of exogenous cytosol. Results indicate that, in contrast to wild-type cytosols, extracts made from rna1-1 mutant cells are unable to support import of the fluorescently labeled substrate into competent nuclei. Immunoblotting demonstrates that these mutant-derived extracts are depleted of Rna1p. However, when purified Rna1p is added back to these extracts the import activity is restored in a dose-dependent manner. These results demonstrate that Rna1p plays a direct role in the import of proteins into the nucleus. C1 DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT BIOCHEM & MOLEC BIOL,HERSHEY,PA 17033. NR 52 TC 152 Z9 152 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP PY 1995 VL 130 IS 5 BP 1017 EP 1026 DI 10.1083/jcb.130.5.1017 PG 10 WC Cell Biology SC Cell Biology GA RR841 UT WOS:A1995RR84100001 PM 7657689 ER PT J AU PELLMAN, D BAGGET, M TU, H FINK, GR AF PELLMAN, D BAGGET, M TU, H FINK, GR TI 2 MICROTUBULE-ASSOCIATED PROTEINS REQUIRED FOR ANAPHASE SPINDLE MOVEMENT IN SACCHAROMYCES-CEREVISIAE SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-CYCLE REGULATION; MITOTIC SPINDLE; FISSION YEAST; BUDDING YEAST; INVITRO REACTIVATION; CHROMOSOME MOVEMENT; SHUTTLE VECTORS; POLE BODY; GENE; MITOSIS AB In many eucaryotic cells, the midzone of the mitotic spindle forms a distinct structure containing a specific set of proteins. We have isolated ASE1, a gene encoding a component of the Saccharomyces cerevisiae spindle midzone. Strains lacking both ASE1 and BIK1, which encodes an S. cerevisiae microtubule-associated protein, are inviable. The analysis of the phenotype of a bik1 ase1 conditional double mutant suggests that BIK1 and ASE1 are not required for the assembly of a bipolar spindle, but are essential for anaphase spindle elongation. The steady-state levels of Ase1p are regulated in a manner that is consistent with a function during anaphase: they are low in G1, accumulate to maximal levels after S phase and then drop as cells exit mitosis. Components of the spindle midzone may therefore be required in vivo for anaphase spindle movement. Additionally, anaphase spindle movement may depend on a dedicated set of genes whose expression is induced at G2/M. C1 WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA. DANA FARBER CANC INST, DEPT HEMATOL ONCOL, BOSTON, MA 02115 USA. CHILDRENS HOSP, BOSTON, MA 02115 USA. FU NIGMS NIH HHS [GM-35010, GM-40266] NR 73 TC 111 Z9 118 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD SEP PY 1995 VL 130 IS 6 BP 1373 EP 1385 DI 10.1083/jcb.130.6.1373 PG 13 WC Cell Biology SC Cell Biology GA RU812 UT WOS:A1995RU81200012 PM 7559759 ER PT J AU DIAMOND, MS ALON, R PARKOS, CA QUINN, MT SPRINGER, TA AF DIAMOND, MS ALON, R PARKOS, CA QUINN, MT SPRINGER, TA TI HEPARIN IS AN ADHESIVE LIGAND FOR THE LEUKOCYTE INTEGRIN MAC-1 (CD11B/CD18) SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MEDIATES NEUTROPHIL ADHESION; CELL-SURFACE; MONOCLONAL-ANTIBODIES; COMPLEMENT RECEPTOR; ENDOTHELIAL-CELLS; SULFATE PROTEOGLYCAN; COUNTER-RECEPTOR; REGULATED EXPRESSION; GLYCOPROTEIN FAMILY; CORE PROTEIN AB Previous studies have demonstrated that the leukocyte integrin Mac-1 adheres to several cell surface and soluble ligands including intercellular adhesion molecule-1, fibrinogen, iC3b, and factor X. However, experiments with Mac-1-expressing transfectants, purified Mac-1, and mAbs to Mac-1 indicate the existence of additional ligands. In this paper, we demonstrate a direct interaction between Mac-1 and heparan sulfate glycans. Heparin affinity resins immunoprecipitate Mac-1, and neutrophils and transfectant cells that express Mac-1 bind to heparin and heparan sulfate, but not to other sulfated glycosaminoglycans. Inhibition studies with mAbs and chemically modified forms of heparin suggest the I domain as a recognition site on Mac-1 for heparin, and suggest that either N- or O-sulfation is sufficient for heparin to bind efficiently to Mac-1. Under conditions of continuous flow in which heparins and E-selectin are cosubstrates, neutrophils tether to E-selectin and form firm adhesions through a Mac-1-heparin interaction. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MONTANA STATE UNIV,DEPT VET MOLEC BIOL,BOZEMAN,MT 59717. RI Parkos, Charles/B-3896-2009 FU NCI NIH HHS [CA31799]; NIAMS NIH HHS [AR40929]; NIGMS NIH HHS [T32 GM007753, T32GM07753-11] NR 75 TC 222 Z9 222 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD SEP PY 1995 VL 130 IS 6 BP 1473 EP 1482 DI 10.1083/jcb.130.6.1473 PG 10 WC Cell Biology SC Cell Biology GA RU812 UT WOS:A1995RU81200020 PM 7559767 ER PT J AU FRIGERI, A GROPPER, MA UMENISHI, F KAWASHIMA, M BROWN, D VERKMAN, AS AF FRIGERI, A GROPPER, MA UMENISHI, F KAWASHIMA, M BROWN, D VERKMAN, AS TI LOCALIZATION OF MIWC AND GLIP WATER CHANNEL HOMOLOGS IN NEUROMUSCULAR, EPITHELIAL AND GLANDULAR TISSUES SO JOURNAL OF CELL SCIENCE LA English DT Article DE WATER TRANSPORT; MERCURIAL-INSENSITIVE WATER CHANNEL; GLIP; IMMUNOLOCALIZATION; AQUAPORIN ID RAT-KIDNEY; COLLECTING TUBULE; GENE-EXPRESSION; APICAL MEMBRANE; CHIP28; PARTICLES; PROTEIN; ARRAYS; CELL; SEGMENTS AB It was shown recently that water channel homologs MIWC (mercurial insensitive water channel) and GLIP (glycerol intrinsic protein) colocalized in basolateral membranes of kidney collecting duct, tracheal and colonic epithelia, and in brain pia mater, We report here an extensive immunolocalization study of MIWC and GLIP in non-epithelial and glandular epithelial tissues in rat, Immunogold electron microscopy confirmed colocalization of MIWC and GLIP in basolateral membrane of principal cells in kidney collecting duct, However, in other epithelia, MIWC but not GLIP was expressed in basolateral membrane of parietal cells in stomach, and in excretory tubules of salivary and lacrimal glands; GLIP but not MIWC was expressed in transitional epithelium of urinary bladder and skin epidermis, Zn the central nervous system, Mn;VC was strongly expressed in the ependymal layer lining the aqueductal system, and in astrocytes throughout the spinal cord and in selected regions of brain, MIWC was also expressed in a plasma membrane pattern in skeletal, but not smooth or cardiac muscle, Neither protein was expressed in small intestine, testis, liver, spleen and nerve, The tissue-specific expression of MIWC suggests a role in fluid transport and/or cell volume regulation in stomach and glandular epithelia, The functional role of MIWC expression in the neuromuscular system and of GLIP expression in skin and urinary bladder is uncertain, The specific cellular sites of MIWC expression (astrocytes, trachea, sarcolemma, gastric parietal cells and kidney principal cells) correspond exactly to sites where orthogonal arrays of particles (OAPs) have been visualized by freeze-fracture electron microscopy, suggesting that MIWC may be the OAF protein. C1 UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT ANESTHESIA,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. OI Frigeri, Antonio/0000-0002-5284-2934 FU NHLBI NIH HHS [HL42368, HL51854]; NIDDK NIH HHS [DK35124] NR 48 TC 285 Z9 296 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 1995 VL 108 BP 2993 EP 3002 PN 9 PG 10 WC Cell Biology SC Cell Biology GA RV181 UT WOS:A1995RV18100008 PM 8537439 ER PT J AU LANDAU, WM DAUBE, JR AMINOFF, MJ BREY, RL BROOKS, BR DEUEL, RK GALABURDA, AM PORTER, JA ROSENBAUM, RB WHITHAM, RH WIGGS, JW AF LANDAU, WM DAUBE, JR AMINOFF, MJ BREY, RL BROOKS, BR DEUEL, RK GALABURDA, AM PORTER, JA ROSENBAUM, RB WHITHAM, RH WIGGS, JW TI NEUROREALITY .1. DEDICATED DEMOLITION OF THE DECADE OF THE BRAIN - THE GENUINE THREAT TO NEUROLOGIC RESEARCH FROM THE ANIMAL RADICAL RIGHT SO JOURNAL OF CHILD NEUROLOGY LA English DT Editorial Material C1 WASHINGTON UNIV,SCH MED,DEPT NEUROL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT PEDIAT,ST LOUIS,MO 63110. MAYO CLIN,DEPT NEUROL,ROCHESTER,MN. UNIV CALIF SAN FRANCISCO,DEPT NEUROL,SAN FRANCISCO,CA 94143. UNIV TEXAS,HLTH SCI CTR,DEPT MED NEUROL,SAN ANTONIO,TX 78285. WILLIAM S MIDDLETON MEM VET ADM MED CTR,NEUROL SERV,MADISON,WI. BETH ISRAEL HOSP,BEHAV NEUROL UNIT,BOSTON,MA 02215. OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. NR 0 TC 2 Z9 2 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON ST, PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 1995 VL 10 IS 5 BP 343 EP 345 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA RV170 UT WOS:A1995RV17000001 PM 7499752 ER PT J AU CULLEN, DJ AF CULLEN, DJ TI FROM THE DESK OF THE EDITOR-IN-CHIEF SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material RP CULLEN, DJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD SEP PY 1995 VL 7 IS 6 BP 447 EP 447 DI 10.1016/0952-8180(95)00131-Z PG 1 WC Anesthesiology SC Anesthesiology GA RU817 UT WOS:A1995RU81700001 ER PT J AU NEWMAN, CB MELMED, S SNYDER, PJ YOUNG, WF BOYAJY, LD LEVY, R STEWART, WN KLIBANSKI, A MOLITCH, ME GAGEL, RF BOYD, AE SHEELER, L COOK, D MALARKEY, WB JACKSON, IMD VANCE, ML THORNER, MO HO, PJ JAFFE, CA FROHMAN, LA KLEINBERG, DL AF NEWMAN, CB MELMED, S SNYDER, PJ YOUNG, WF BOYAJY, LD LEVY, R STEWART, WN KLIBANSKI, A MOLITCH, ME GAGEL, RF BOYD, AE SHEELER, L COOK, D MALARKEY, WB JACKSON, IMD VANCE, ML THORNER, MO HO, PJ JAFFE, CA FROHMAN, LA KLEINBERG, DL TI SAFETY AND EFFICACY OF LONG-TERM OCTREOTIDE THERAPY OF ACROMEGALY - RESULTS OF A MULTICENTER TRIAL IN 103 PATIENTS - A CLINICAL RESEARCH-CENTER STUDY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ANALOG SMS 201-995; SECRETING PITUITARY-ADENOMAS; CONTINUOUS SUBCUTANEOUS INFUSION; GROWTH-HORMONE RESPONSES; CECUM TRANSIT-TIME; SOMATOSTATIN ANALOG; DOSE-RESPONSE; GALL-STONES; RESISTANT; BROMOCRIPTINE AB One hundred and three acromegalic patients from 14 medical centers were enrolled in this study to determine the efficacy and safety of the somatastatin analog, octreotide acetate, during long term treatment. Seventy percent of the patients had undergone previous surgery or radiation treatment. Octreotide was initiated at a dose of 100 mu g, sc, every 8 h and gradually increased to a maximum of 1500 mu g daily depending upon the individual patient's clinical and biochemical response [GH and insulin-like growth factor I (IGF-I) reduction]. The mean duration of treatment was 24 months (range, 3-30 months). However, most patients were treated for a mean of 30 months, because this study took place after an initial 6-month study previously reported. Mean serum GH fell from 30.9 mu g/L (range, 2.7-350) to 5.7 mu g/L (range, 0.6-59) at the 3 month visit and remained suppressed (P < 0.001). Plasma IGF-I concentrations were also significantly reduced and remained in the normal range for at least half of the treatment visits in 56 of 87 patients (64%) treated for 12-30 months. Patients with higher initial GH concentrations were less likely to normalize IGF-I concentrations during treatment (P < 0.001). There was no evidence of drug tachyphylaxis in those patients who continued taking stable doses of medication. With some exceptions, dose increments above 800 mu g daily in 31 patients did not provide additional benefit in terms of GH and IGF-I reduction. Headache, excessive perspiration, fatigue, and joint pain were ameliorated in 83-95% of patients. Mean finger circumference was decreased significantly at the 12 month visit (P < 0.05). The most common adverse events reported were diarrhea, abdominal discomfort, loose stools, and nausea; these symptoms usually disappeared within 3 months of treatment. Five patients discontinued octreotide because of adverse events. Of 102 patients with normal baseline ultrasound examinations of the gallbladder, 24 patients (23.5%) developed gallstones (usually during the first year of treatment), and 21 patients developed sludge alone. Gallstone formation was not related to the dose of octreotide. Most patients with cholelithiasis were asymptomatic, and none developed cholecystitis. These observations suggest that octreotide is a valuable long term medical treatment for acromegaly. C1 VET AFFAIRS MED CTR, NEW YORK, NY 10010 USA. CEDARS SINAI MED CTR, DIV ENDOCRINOL & METAB, LOS ANGELES, CA 90048 USA. UNIV PENN, SCH MED, DIV ENDOCRINOL, PHILADELPHIA, PA 19104 USA. MAYO CLIN & MAYO FDN, DEPT MED, ROCHESTER, MN 55905 USA. SANDOZ PHARMACEUT CORP, E HANOVER, NJ 07936 USA. MASSACHUSETTS GEN HOSP, NEUROENDOCRINE UNIT, BOSTON, MA 02114 USA. NORTHWESTERN UNIV, SCH MED, CTR ENDOCRINOL METAB & MOLEC MED, CHICAGO, IL 60611 USA. UNIV TEXAS, MD ANDERSON CANC CTR, ENDOCRINOL SECT, HOUSTON, TX 77030 USA. TUFTS UNIV NEW ENGLAND MED CTR, DIV ENDOCRINOL, BOSTON, MA 02111 USA. OREGON HLTH SCI UNIV, DIV ENDOCRINOL, PORTLAND, OR 97201 USA. INNOVA MED SERV, BROOKLYN, OH 44144 USA. OHIO STATE UNIV, MED CTR, DEPT MED, COLUMBUS, OH 43210 USA. BROWN UNIV, RHODE ISL HOSP, DEPT MED, PROVIDENCE, RI 02903 USA. UNIV VIRGINIA, MED CTR, DEPT MED, CHARLOTTESVILLE, VA 22908 USA. ROYAL N SHORE HOSP, KOLLING INST MED RES, ST LEONARDS, NSW 2065, AUSTRALIA. UNIV MICHIGAN, MED CTR, DEPT MED, ANN ARBOR, MI 48109 USA. UNIV ILLINOIS, DEPT MED, CHICAGO, IL 60612 USA. RP NEWMAN, CB (reprint author), NYU, DEPT MED, 423 E 23RD ST, 16043 W, NEW YORK, NY 10010 USA. OI Newman, Connie/0000-0001-9144-056X FU NCRR NIH HHS [5-MO1-RR-00040, 5-MO1-RR-00096-32AI, RR-0048] NR 69 TC 180 Z9 187 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 SEP PY 1995 VL 80 IS 9 BP 2768 EP 2775 DI 10.1210/jc.80.9.2768 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA RU633 UT WOS:A1995RU63300035 PM 7673422 ER PT J AU HEAGY, W DUCA, K FINBERG, RW AF HEAGY, W DUCA, K FINBERG, RW TI ENKEPHALINS STIMULATE LEUKEMIA-CELL MIGRATION AND SURFACE EXPRESSION OF CD9 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE ENKEPHALINS; OPIOID PEPTIDES; CELL MOVEMENT; PRE-B CELL; LEUKEMIA; LEUKOCYTE-ADHESION RECEPTORS ID NEUTRAL ENDOPEPTIDASE 24.11; OPIOID-PEPTIDES; MONOCLONAL-ANTIBODIES; POLYMORPHONUCLEAR LEUKOCYTES; BETA-ENDORPHIN; IMMUNE-SYSTEM; RECEPTORS; PROTEIN; ANTIGEN; MODULATION AB Opioid peptides have been implicated in the regulation of tumor growth and biology; however, little attention has been given to the mechanisms that are involved. In this study we show that physiological concentrations of the endogenous opioid neuropeptide methionine-enkephalin (MET-ENK) and the synthetic enkephalins D-Ala(2),Me-Phe(4),Gly(ol)(5) and D-Ala(2)D-Leu(5) are stimulants for the in vitro migration of pre-B acute lymphoblastoid leukemia (ALL) cells. Activation of the human pre-B ALL cell lines NALM 6 and LAZ 221 with MET-ENK resulted in both an increase in their migration and an augmentation in the surface expression of the leukemia cell marker CD9. The opiate receptor antagonist naloxone reversed these enkephalin-induced effects on the leukemia cells, When the pre-B ALL cells were preincubated with an anti-CD9 mAb before challenge with MET-ENK their migration to the enkephalin was markedly reduced, These studies show that endogenous and synthetic opioid peptides are stimulants for pre-B ALL cell migration and suggest that CD9 is important in the regulation of leukemia cell motility. C1 DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 FU PHS HHS [R01A129657] NR 45 TC 14 Z9 14 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1366 EP 1374 DI 10.1172/JCI118171 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300024 PM 7657811 ER PT J AU GIORGINO, F SMITH, RJ AF GIORGINO, F SMITH, RJ TI DEXAMETHASONE ENHANCES INSULIN-LIKE GROWTH-FACTOR-I EFFECTS ON SKELETAL-MUSCLE CELL-PROLIFERATION - ROLE OF SPECIFIC INTRACELLULAR SIGNALING PATHWAYS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GLUCOCORTICOIDS; INSULIN-LIKE GROWTH FACTOR-I RECEPTOR; INSULIN RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; SHC ID FACTOR-BINDING PROTEINS; IGF-I; PHOSPHATIDYLINOSITOL 3'-KINASE; TYROSINE PHOSPHORYLATION; HUMAN-FIBROBLASTS; SHC PROTEINS; RECEPTOR; DIFFERENTIATION; IRS-1; SUBSTRATE AB IGF-I stimulation of cell proliferation and c-Fos expression in skeletal muscle cells is markedly enhanced by dexamethasone, The effect of dexamethasone is not mediated by changes in IGF-binding proteins, as evidenced by similar effects of dexamethasone on the actions of insulin, PDGF-BB, and the IGF-I analogue long R(3)IGF-I. Dexamethasone also does not alter autocrine IGF-II secretion by muscle cells. To investigate the mechanism of the augmentation of IGF-I action, the effects of dexamethasone on intracellular IGF-I signaling pathways were determined. In dexamethasone-treated cells, the levels of IGF-I receptor tyrosine phosphorylation and receptor-associated phosphatidylinositol 3-kinase activity were increased, Dexamethasone-treated cells also shelved increased and prolonged tyrosine phosphorylation of the She proteins. In contrast, dexamethasone decreased both tyrosine phosphorylation and expression of insulin receptor substrate 1 (IRS-1) and IRS-1-associated phosphatidylinositol 3-kinase activity. Thus, distinct signaling pathways activated by the IGF-I receptor in skeletal muscle cells are differentially regulated by dexamethasone. Potentiation of IGF-I action correlates with increased IGF-I receptor-associated phosphatidylinositol 3-kinase activity and tyrosine phosphorylation of She, but appears to be independent of activation of the IRS-1/phosphatidylinositol 3-kinase signaling pathway. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 FU NIDDK NIH HHS [DK/GM48503, DK43038]; NIGMS NIH HHS [GM36428] NR 66 TC 50 Z9 51 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 1995 VL 96 IS 3 BP 1473 EP 1483 DI 10.1172/JCI118184 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA RR853 UT WOS:A1995RR85300037 PM 7544807 ER PT J AU GEORGE, JS AINE, CJ MOSHER, JC SCHMIDT, DM RANKEN, DM SCHLITT, HA WOOD, CC LEWINE, JD SANDERS, JA BELLIVEAU, JW AF GEORGE, JS AINE, CJ MOSHER, JC SCHMIDT, DM RANKEN, DM SCHLITT, HA WOOD, CC LEWINE, JD SANDERS, JA BELLIVEAU, JW TI MAPPING FUNCTION IN THE HUMAN BRAIN WITH MAGNETOENCEPHALOGRAPHY, ANATOMICAL MAGNETIC-RESONANCE-IMAGING, AND FUNCTIONAL MAGNETIC-RESONANCE-IMAGING SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Review DE BRAIN MAPPING; MAGNETOENCEPHALOGRAPHY; FUNCTIONAL MAGNETIC RESONANCE IMAGING; ANATOMICAL CONSTRAINTS; MULTIMODALITY IMAGING ID BIOMAGNETIC INVERSE PROBLEM; HUMAN VISUAL-CORTEX; EVOKED-POTENTIALS; SENSORY STIMULATION; NEURONAL-ACTIVITY; LOCALIZATION; DIPOLE; MODEL; HEAD; IDENTIFICATION AB Integrated analyses of human anatomical and functional measurements offer a powerful paradigm for human brain mapping, Magnetoencephalography (MEG) and EEG provide excellent temporal resolution of neural population dynamics as well as capabilities for source localization. Anatomical magnetic resonance imaging (MRI) provides excellent spatial resolution of head and brain anatomy, whereas functional MRI (fMRI) techniques provide an alternative measure of neural activation based on associated hemodynamic changes. These methodologies constrain and complement each other and can thereby improve our interpretation of functional neural organization. We have developed a number of computational tools and techniques for the visualization, comparison, and integrated analysis of multiple neuroimaging techniques. Construction of geometric anatomical models from volumetric MRI data allows improved models of the head volume conductor and can provide powerful constraints for neural electromagnetic source modeling. These approaches, coupled to enhanced algorithmic strategies for the inverse problem, can significantly enhance the accuracy of source-localization procedures. We have begun to apply these techniques for studies of the functional organization of the human visual system. Such studies have demonstrated multiple, functionally distinct visual areas that can be resolved on the basis of their locations, temporal dynamics, and differential sensitivity to stimulus parameters. Our studies have also produced evidence of internal retinotopic organization in both striate and extrastriate visual areas but have disclosed organizational departures from classical models. Comparative studies of MEG and fMRI suggest a reasonable but imperfect correlation between electrophysiological and hemodynamic responses. We have demonstrated a method for the integrated analysis of fMRI and MEG, and we outline strategies for improvement of these methods. By combining multiple measurement techniques, we can exploit the complementary strengths and transcend the limitations of the individual neuroimaging methods. C1 ALBUQUERQUE FED REG MED CTR,CTR MAGNET RESONANCE IMAGING,ALBUQUERQUE,NM. MASSACHUSETTS GEN HOSP,CTR NMR,BOSTON,MA. ALBUQUERQUE FED REG MED CTR,CTR MAGNET SOURCE IMAGING,ALBUQUERQUE,NM. RP GEORGE, JS (reprint author), LOS ALAMOS NATL LAB,BIOPHYS GRP,MS M-715,LOS ALAMOS,NM 87545, USA. FU NEI NIH HHS [EY08610] NR 92 TC 152 Z9 155 U1 2 U2 15 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD SEP PY 1995 VL 12 IS 5 BP 406 EP 431 DI 10.1097/00004691-199509010-00002 PG 26 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA RW073 UT WOS:A1995RW07300002 PM 8576388 ER PT J AU CLARK, JW CHABNER, BA AF CLARK, JW CHABNER, BA TI SURAMIN AND PROSTATE-CANCER - WHERE DO WE GO FROM HERE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PHASE-II; CELLS RP CLARK, JW (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 30 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1995 VL 13 IS 9 BP 2155 EP 2157 PG 3 WC Oncology SC Oncology GA RT917 UT WOS:A1995RT91700003 PM 7666073 ER PT J AU SCULLY, SP TEMPLE, HT OKEEFFE, RJ SCARBOROUGH, MT MANKIN, HJ GEBHARDT, MC AF SCULLY, SP TEMPLE, HT OKEEFFE, RJ SCARBOROUGH, MT MANKIN, HJ GEBHARDT, MC TI ROLE OF SURGICAL RESECTION IN PELVIC EWINGS-SARCOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID THERAPY; BONE AB Purpose: The improved survival in patients with Ewing's sarcoma over the past two decades has placed increased importance on achievement of local disease control, Ewing's sarcoma that arises in the pelvis has been recognized to have a worse prognosis than that in the appendicular skeleton, and the role of surgical resection in these cases remains controversial. The current study attempts to identify a benefit to surgical resection in these patients. Methods: We retrospectively examined 39 patients who presented with Ewing's sarcoma in a pelvic location, all of whom were treated systemically with chemotherapy, Twenty patients received radiation only as a means of local control, and 19 underwent resection with or without radiation therapy, The patients were evaluated with end points of disease-free survival and overall survival for a minimum of 24 months and a mean of 58 months. Results: There was an even distribution among patients who underwent surgical resection for local control as compared with those who received only radiation therapy with respect to age, site, date of treatment, and stage of disease, Despite uncontrolled biases including tumor size and response to chemotherapy that would be expected to favor patients who undergo resection, surgery in addition to or in substitution for radiation therapy did not result in a statistically significant increase in disease-free survival or overall survival. Local disease control was comparable between those who underwent resection and those who did not: three patients in each group developed a local recurrence. Conclusion: Currently, morbidity of surgical resection should be weighed against the efficacy and secondary complications of radiation therapy in the decision-making process for local disease control, The issue of whether overall survival and local disease control is improved in patients who undergo surgical resection remains controversial and may require a prospective randomized trial to be answered definitively. (C) 1995 by American Society of Clinical Oncology. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED ONCOL UNIT,BOSTON,MA. WALTER REED ARMY MED CTR,WASHINGTON,DC. UNIV FLORIDA,GAINESVILLE,FL. UNIV ROCHESTER,ROCHESTER,NY. RP SCULLY, SP (reprint author), DUKE UNIV,MED CTR,BOX 3312,DURHAM,NC 27710, USA. NR 20 TC 55 Z9 56 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 1995 VL 13 IS 9 BP 2336 EP 2341 PG 6 WC Oncology SC Oncology GA RT917 UT WOS:A1995RT91700026 PM 7666092 ER PT J AU CHENEY, ML GLIKLICH, R LI, KK TOPF, P MONTGOMERY, W AF CHENEY, ML GLIKLICH, R LI, KK TOPF, P MONTGOMERY, W TI MIDFOREHEAD INCISION - AN APPROACH TO THE FRONTAL-SINUS AND UPPER FACE SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article DE FRONTAL SINUS; MIDFOREHEAD INCISION; CORONAL INCISION; FOREHEAD RECONSTRUCTION; CRANIOPLASTY AB The coronal incision has established itself as the principal surgical approach to the forehead. It allows for a well-hidden scar and a wide field of surgical exposure. The midforehead incision, described in the brow-lift literature, is a cosmetically acceptable alternative to the coronal incision for patients with forehead wrinkles or who are at risk for male pattern baldness. In an analysis of 33 consecutive open frontal sinus procedures, we compared patients who underwent a coronal approach to a midforehead approach for operative time, blood loss, length of hospital stay, and cosmetic result. There was a trend toward decreased operative time and decreased blood loss with the midforehead approach. The cosmetic result was acceptable in all patients. We advocate the use of a midforehead approach to the frontal sinus in patients with deep forehead creases and with hairline recession and elderly or infirmed patients who cannot tolerate prolonged procedures or significant blood loss. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT SURG,DIV OTOLARYNGOL HEAD & NECK SURG,ROCHESTER,NY. RP CHENEY, ML (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02114, USA. NR 7 TC 10 Z9 10 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD SEP PY 1995 VL 6 IS 5 BP 408 EP 411 DI 10.1097/00001665-199509000-00018 PG 4 WC Surgery SC Surgery GA RV383 UT WOS:A1995RV38300017 PM 9020725 ER PT J AU GOLLOB, JA LI, J REINHERZ, EL RITZ, J AF GOLLOB, JA LI, J REINHERZ, EL RITZ, J TI CD2 REGULATES RESPONSIVENESS OF ACTIVATED T-CELLS TO INTERLEUKIN-12 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DOSE RECOMBINANT INTERLEUKIN-2; STIMULATORY FACTOR NKSF; LYMPHOCYTE-T; ADHESION MOLECULES; PROLONGED INFUSION; GAMMA PRODUCTION; RECEPTOR; EXPRESSION; IL-12; LFA-3 AB Interleukin (IL) 12 is a 70-kD heterodimeric cytokine produced by antigen-presenting cells (APCs) such as macrophages in response to infectious pathogens and interferon (IFN) gamma. The varied immunomodulatory effects of IL-12 include the stimulation of proliferation and IFN-gamma production by T cells, and it also has a central role in the development of the T helper cell type 1 immune phenotype. We undertook the production of antibodies capable of modulating the response of T cells to IL-12, and in the process we discovered two antibodies that inhibited the ability of IL-12 to stimulate T cell proliferation. In this report, we demonstrate that these antibodies recognize CD2, and we show how antibodies directed toward either the adhesion domain of CD2 or its ligand, CD58, specifically inhibit IL-12-induced proliferation and IFN-gamma production by phytohemagglutinin-activated T cells, leaving the response to IL-2 unaffected. A three-to fourfold reduction in proliferation and IFN-gamma production was observed at IL-12 concentrations as high as 1 nM, with complete inhibition occurring at less than or equal to 1 pM. This novel effect is not directly mediated at the level of the IL-12 receptor, as shown by the inability of these antibodies to block IL-12 binding to activated T cells. Furthermore, by using activating pairs of CD2 antibodies, we show that CD2 stimulation strongly synergizes with IL-12, even at 0.1 pM, in inducing both T cell proliferation and IFN-gamma production. Cytolytic T lymphocyte-associated antigen 4-immunoglobulin-mediated inhibition of the B7/CD28 interaction did not affect the T cell response to either IL-12 or IL-2, but the removal of APCs selectively diminished the proliferative response to IL-12. Based on this data, we hypothesize that CD2 has a central role in an IL-12/IFN-gamma positive feedback loop between T cell and APC, providing the key functional link via a CD2/CD58 interaction that controls T cell responsiveness to IL-12. This model provides a basis for future investigations aimed at defining the signaling mechanisms that mediate this cytokine-specific regulatory effect of CD2, and it offers insight into how a cytokine receptor and distinct adhesion molecule can interact to modulate responsiveness to that cytokine. In addition, it underscores the possibility that the clinical potential of an immunomodulatory drug like IL-12 may be governed by the presence or absence of specific costimulation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,IMMUNOBIOL LAB,BOSTON,MA 02115. RP GOLLOB, JA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,MAYER BLDG 726,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619]; NIAID NIH HHS [AI21226] NR 36 TC 81 Z9 83 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1995 VL 182 IS 3 BP 721 EP 731 DI 10.1084/jem.182.3.721 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RQ754 UT WOS:A1995RQ75400010 PM 7544396 ER PT J AU ARAMBURU, J AZZONI, L RAO, A PERUSSIA, B AF ARAMBURU, J AZZONI, L RAO, A PERUSSIA, B TI ACTIVATION AND EXPRESSION OF THE NUCLEAR FACTORS OF ACTIVATED T-CELLS, NFATP AND NFATC, IN HUMAN NATURAL-KILLER-CELLS - REGULATION UPON CD16 LIGAND-BINDING SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; CIS-ACTING ELEMENT; FACTOR-ALPHA GENE; KAPPA-B SITE; CYCLOSPORINE-A; NF-AT; INTERLEUKIN-2 PROMOTER; SIGNAL TRANSDUCTION; LYMPHOKINE GENES; TRANSCRIPTION AB The putative factors that couple the signal transduction from surface receptors to the activation of cytokine synthesis in natural killer (NK) cells have not been elucidated. We report here that the nuclear factor of activated T cells (NFATp), a cyclosporin A (CsA)-sensitive factor that regulates the transcription of several cytokines, mediates CD16-induced activation of cytokine genes in human NK cells. CD16 (Fc gamma RIIIA)-induced expression of cytokine mRNA in NK cells occurs via a CsA-sensitive and Ca2+-dependent mechanism. Stimulation of NK cells with CD16 ligands induces NFAT-like DNA binding activity in the nuclear extracts from these cells, as detected in electrophoretic mobility shift assays. This occurs with fast kinetics after stimulation, via a CsA-sensitive and Ca2+-dependent mechanism that does not require de novo protein synthesis. NK cell NFAT is present in the cytosol of nonstimulated cells, migrates to the nucleus upon stimulation, and can associate with AP-1. Two distinct molecules, NFATp, and NFATc, have been reported to mediate NFAT activity. The results of supershift assays using NFATp- and NFATc-specific antibodies indicate that NK cell activation early after CD16 ligand binding involves primarily if not exclusively, NFATp, and Western blot analysis shows that this has the same electrophoretic mobility (similar to 120 kD) as that of T lymphocytes. NK cells do not express NFATc constitutively, but NFATc mRNA accumulation is induced in these cells within 2 h of stimulation with CD16 ligands. However, supershift assays using the available mAb recognizing the T cell NFATc revealed no detectable NFATc protein in nuclear and cytoplasmic extracts from CD16- or phorbol ester-stimulated cells at any time tested, up to 4 h. These results provide the first direct evidence that both CsA-sensitive transcription factors, NFATp and NFATc, are expressed in human NK cells, and that their activation and/or expression can be regulated in primary cells by a single stimulus that, in the case of CD16 in NK cells, results in early activation of NFATp and subsequently induced expression of NFATc mRNA. C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. CHILDRENS HOSP,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. RI Aramburu, J/G-8991-2014 OI Aramburu, J/0000-0001-9279-9523 FU NCI NIH HHS [CA37155, CA45284] NR 50 TC 98 Z9 99 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1995 VL 182 IS 3 BP 801 EP 810 DI 10.1084/jem.182.3.801 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RQ754 UT WOS:A1995RQ75400018 PM 7650486 ER PT J AU TIAN, QS TAUPIN, JL ELLEDGE, S ROBERTSON, M ANDERSON, P AF TIAN, QS TAUPIN, JL ELLEDGE, S ROBERTSON, M ANDERSON, P TI FAS-ACTIVATED SERINE THREONINE KINASE (FAST) PHOSPHORYLATES TIA-1 DURING FAS-MEDIATED APOPTOSIS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RIBONUCLEOTIDE REDUCTASE ICP10; GRANULE-ASSOCIATED PROTEIN; MONOCLONAL-ANTIBODY TIA-1; LARGE SUBUNIT; CD8+ LYMPHOCYTES; CELLS; EXPRESSION; IDENTIFICATION; ANTIGEN; SYSTEM AB We have identified a serine/threonine kinase that is rapidly activated during Fas-mediated apoptosis. Fas-activated serine/threonine kinase (FAST) is phosphorylated on serine and threonine residues in Jurkat cells. In response to Fas ligation, it is rapidly dephosphorylated and concomitantly activated to phosphorylate TIA-1, a nuclear RNA-binding protein that has been implicated as an effector of apoptosis. Phosphorylation of TIA-1 precedes the onset of DNA fragmentation, suggesting a role in signaling downstream events in the apoptotic program. Our results introduce FAST and TIA-1 as components of a molecular cascade involved in signaling Fas-mediated apoptosis. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DEPT RHEUMATOL IMMUNOL,DIV TUMOR IMMUNOL,BOSTON,MA 02115. BAYLOR COLL MED,HOWARD HUGHES MED INST,DEPT RHEUMATOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,HOWARD HUGHES MED INST,DEPT BIOCHEM,HOUSTON,TX 77030. DEPT BIOCHEM,HOUSTON,TX 77030. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI33600] NR 49 TC 129 Z9 139 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1995 VL 182 IS 3 BP 865 EP 874 DI 10.1084/jem.182.3.865 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA RQ754 UT WOS:A1995RQ75400024 PM 7544399 ER PT J AU LEONG, GB SILVA, JA AF LEONG, GB SILVA, JA TI PSYCHIATRIC-LEGAL ANALYSIS OF CRIMINAL DEFENDANTS CHARGED WITH MURDER - A SAMPLE WITHOUT MAJOR MENTAL DISORDER SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE PSYCHIATRY; HOMICIDE; MURDER; SUBSTANCE ABUSE; VIOLENCE; AGGRESSION; CULTURAL FACTORS AB A sample of 31 criminal defendants who were charged with murder but without major mental disorder was studied. The sample was derived from a large urban multi-ethnic, multi-cultural community pool. Subject characteristics and information about the homicide and decedents are described. Suggestions for further study are briefly discussed. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 26 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 1995 VL 40 IS 5 BP 858 EP 861 PG 4 WC Medicine, Legal SC Legal Medicine GA RX718 UT WOS:A1995RX71800031 PM 7595330 ER PT J AU LEONG, GB SILVA, JA WEINSTOCK, R AF LEONG, GB SILVA, JA WEINSTOCK, R TI ANOTHER COURTROOM ASSAULT ON THE CONFIDENTIALITY OF THE PSYCHOTHERAPIST-PATIENT RELATIONSHIP SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE PSYCHIATRY; PSYCHOTHERAPY; PRIVILEGE; CONFIDENTIALITY; PRIVACY AB The therapeutic and legal protections afforded by California's psychotherapist-patient privilege have become increasingly eroded in such recent cases as People v. Wharton and Menendez v. Superior Court. In another capital case, People v. Webb, the California Supreme Court further erodes this privilege in regard to the private (confidential) treatment records of a prosecution witness. The Webb case and its possible implications are explored. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD SEP PY 1995 VL 40 IS 5 BP 862 EP 864 PG 3 WC Medicine, Legal SC Legal Medicine GA RX718 UT WOS:A1995RX71800032 PM 7595331 ER PT J AU DISALVO, TG NARULA, J COSIMI, AB KECK, S DEC, GW SEMIGRAN, MJ AF DISALVO, TG NARULA, J COSIMI, AB KECK, S DEC, GW SEMIGRAN, MJ TI ACTINOMYCIN-D IS AN EFFECTIVE ADJUNCTIVE IMMUNOSUPPRESSIVE AGENT IN RECURRENT CARDIAC ALLOGRAFT-REJECTION SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article AB Background: Actinomycin D is a potent cytotoxic agent which inhibits DNA transcription by DNA-dependent RNA polymerases and has previously been used as adjunctive immunosuppressive agent for refractory renal allograft rejection. Methods: To assess the efficacy of actinomycin D in cardiac allograft rejection, we studied seven patients with recurrent cellular or humoral rejection. All patients received intravenous actinomycin D 5 mu g/kg every 6 weeks. Results: During the 6-months after initiation of actinomycin D treatment, the mean number of treated cellular or humoral rejection episodes per patient (0.14) and the mean number of International Society for Heart and Lung Transplantation grade 2 or higher endomyocardial biopsy specimens per patient (0.3) were lower compared with those observed during the 6-month pre-actinomycin D period (1.6 and 2.6, respectively). By 6 months after initiation of actinomycin D, all seven patients were receiving lower daily maintenance doses of corticosteroids. The mean total corticosteroid dose after actinomycin D administration per patient per month (615 +/- 177 mg) was significantly lower than the pre-actinomycin D dose (1012 +/- 347 mg; p = 0.019). No patient had significant adverse effects. Conclusions: Actinomycin D is an effective immunosuppressive agent for prevention of recurrent cellular or humoral rejection after cardiac allograft rejection. The corticosteroid sparing effect of actinomycin D may be of particular benefit. C1 MASSACHUSETTS GEN HOSP,CTR HEART FAILURE & CARDIAC TRANSPLANTAT,BOSTON,MA 02114. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD SEP-OCT PY 1995 VL 14 IS 5 BP 955 EP 962 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA RY627 UT WOS:A1995RY62700020 PM 8800733 ER PT J AU VESCIO, RA CAO, J HONG, CH LEE, JC WU, CH DANIELIAN, MD WU, V NEWMAN, R LICHTENSTEIN, AK BERENSON, JR AF VESCIO, RA CAO, J HONG, CH LEE, JC WU, CH DANIELIAN, MD WU, V NEWMAN, R LICHTENSTEIN, AK BERENSON, JR TI MYELOMA IG HEAVY-CHAIN-V REGION SEQUENCES REVEAL PRIOR ANTIGENIC SELECTION AND MARKED SOMATIC MUTATION BUT NO INTRACLONAL DIVERSITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MALIGNANT PLASMA-CELL; MULTIPLE-MYELOMA; BONE-MARROW; GERMINAL-CENTERS; IMMUNE-RESPONSE; ANTIBODY DIVERSITY; CLONAL EXPANSION; B-CELLS; GENE; REPERTOIRE AB The Ig V-H region sequence in 48 patients with multiple myeloma (MM) was analyzed to characterize the malignant cell of origin. The sequences were obtained after amplification of bone marrow cDNA by using V-H family-specific and C-H primers, then compared with either directly sequenced patient germ-line or published V, gene sequences to assay for somatic mutation. Because somatic hypermutation of the V, gene occurs late in B cell development, its presence has been helpful in determining the cell of origin in other B cell malignancies. Overall, a median of 8.2% of the nucleotides had evidence of substitution within each V-H gene sequence (range = 2.7% to 16.5%), which is more prevalent than in any other reported tumor type. Strong evidence of prior antigenic selection pressure was also evident. The ratio of nucleotide substitutions that resulted in amino acid replacement was significantly higher in the complementarity-determining region than in the framework region (3.25 vs 1.56, respectively; p < 0.00005). No V-H gene intraclonal diversity was noted, despite sequencing multiple clones (3-16) from each patient, nor was there evidence of further VH gene somatic mutation over the course of three patients' disease. These findings strongly imply that the malignant clone in MM evolves from a cell late in B cell development. C1 W LOS ANGELES DEPT VET AFFAIRS MED CTR,DIV GASTROENTEROL,LOS ANGELES,CA 90073. IDEC PHARMACEUT CORP,SAN DIEGO,CA 92121. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV HEMATOL ONCOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,JONSSON COMPREHENS CANC CTR,LOS ANGELES,CA 90024. RP VESCIO, RA (reprint author), W LOS ANGELES DEPT VET AFFAIRS MED CTR,DIV HEMATOL ONCOL,BLDG 500,ROOM 4237 111H,LOS ANGELES,CA 90073, USA. NR 62 TC 115 Z9 116 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1995 VL 155 IS 5 BP 2487 EP 2497 PG 11 WC Immunology SC Immunology GA RP743 UT WOS:A1995RP74300022 PM 7650379 ER PT J AU OGAWA, N DANG, H LAZARIDIS, K MCGUFF, HS AUFDEMORTE, TB TALAL, N AF OGAWA, N DANG, H LAZARIDIS, K MCGUFF, HS AUFDEMORTE, TB TALAL, N TI ANALYSIS OF TRANSFORMING GROWTH-FACTOR-BETA AND OTHER CYTOKINES IN AUTOIMMUNE EXOCRINOPATHY (SJOGRENS-SYNDROME) SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID MYELIN BASIC-PROTEIN; EPSTEIN-BARR VIRUS; II COLLAGEN; MONOCLONAL-ANTIBODIES; RHEUMATOID-ARTHRITIS; ORAL TOLERIZATION; IMMUNE-RESPONSES; LYMPHOID-CELLS; EXPRESSION; SUPPRESSION AB Cytokines play a major role in tissue destruction caused by autoimmune dysregulation, In Sjogren's syndrome (SS) patients, salivary glands are the target organs for autoimmune tissue damage, In the present study, reverse trancriptase-polymerase chain reaction (RT-PCR) was used to look for cytokine mRNA expressed in SS salivary glands, Focus score was used to determine the severity of the lesions, Cytokine production in supernatants of the salivary gland cell culture was measured by enzyme-linked immunosorbent assay (ELISA), Immunohistochemical staining was used to identify the local presence of transforming growth factor beta (TGF-beta), Interleukin (IL)-2, IL-6, and IL-10 mRNA were expressed in moderate to severe SS salivary gland lesions, TGF-P mRNA was constitutively expressed in normal and SS salivary glands, In SS salivary gland cell cultures, IL-6 and IL-10 proteins were produced, TGF-beta production was reduced in high focus score SS glands, Normal and minimally involved SS salivary gland ductal epithelium and acinar cells were found to produce TGF-beta by immunostaining, In conclusion, an excess production of IL-2, IL-6, and IL-10 and a reduced production of the immunosuppressive cytokine, TGF-beta, may be responsible for the progression of the salivary gland lesion in SS, Specific immunotherapy can now be designed based on mechanisms to correct this cytokine imbalance and benefit patients with autoimmune diseases, such as SS. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP OGAWA, N (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [DE10863, DE09311] NR 57 TC 39 Z9 39 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD SEP PY 1995 VL 15 IS 9 BP 759 EP 767 DI 10.1089/jir.1995.15.759 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA RW068 UT WOS:A1995RW06800002 PM 8536103 ER PT J AU SCHALLER, J HEILIGENHAUS, A ENGELBRECHT, S FOSTER, CS AF SCHALLER, J HEILIGENHAUS, A ENGELBRECHT, S FOSTER, CS TI DETECTION OF EOSINOPHIL CATIONIC PROTEIN IN ACTIVE OCULAR CICATRICIAL PEMPHIGOID SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 ST BARBARA HOSP,DEPT DERMATOL,D-47167 DUISBURG,GERMANY. UNIV ESSEN GESAMTHSCH,DEPT OPHTHALMOL,D-45122 ESSEN,GERMANY. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1995 VL 105 IS 3 BP 482 EP 482 PG 1 WC Dermatology SC Dermatology GA RU399 UT WOS:A1995RU39900230 ER PT J AU KONRADI, C COLE, RL GREEN, D SENATUS, P LEVEQUE, JC POLLACK, AE GROSSBARD, SJ HYMAN, SE AF KONRADI, C COLE, RL GREEN, D SENATUS, P LEVEQUE, JC POLLACK, AE GROSSBARD, SJ HYMAN, SE TI ANALYSIS OF THE PROENKEPHALIN 2ND-MESSENGER-INDUCIBLE ENHANCER IN RAT STRIATAL CULTURES SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PROENKEPHALIN; STRIATUM; PRIMARY CULTURE; C-FOS; CYCLIC AMP RESPONSE ELEMENT BINDING PROTEIN; PHOSPHORYLATION ID LEUCINE ZIPPER PROTEINS; TRANS-ACTING FACTOR; PROTO-ONCOGENE FOS; CYCLIC-AMP; ADENOSINE-A2 RECEPTOR; GENE-TRANSCRIPTION; ENKEPHALIN CONTENT; BINDING PROTEIN; RNA; ELEMENT AB We have previously shown that in cell extracts from rat striatum, cyclic AMP response element (CRE) binding protein (CREB), rather than AP-1 proteins, preferentially interacts with the CRE-2 element of the proenkephalin second messenger-inducible enhancer, even under conditions in which AP-1 proteins are highly induced. Here we use primary striatal cultures to permit a more detailed analysis of CRE-2 function and protein binding in relevant neural cell types. By transfection we find that in primary striatal cultures, as in transformed cell lines, the CRE-1 and CRE-2 elements are required for significant induction by cyclic AMP. We report that cyclic AMP induction of the proenkephalin gene in striatal cultures is protein synthesis independent, excluding a role for newly synthesized proteins like c-Fos. We also show that cyclic AMP induces CREB phosphorylation and that phosphorylated CREB interacts strongly with CRE-2 and weakly with CRE-1. The predominant protein bound to CRE-1 is not CREB, however, and remains to be identified. Despite some prior predictions, we do not find a role for c-Fos in cyclic AMP regulation of proenkephalin gene expression in neurons. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC & DEV NEUROSCI LAB,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MOLEC NEUROBIOL LAB,BOSTON,MA. FU NIDA NIH HHS [DA 07134]; NIMH NIH HHS [MH00892] NR 43 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1995 VL 65 IS 3 BP 1007 EP 1015 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RQ571 UT WOS:A1995RQ57100007 PM 7643080 ER PT J AU NEUMAR, RW DEGRACIA, DJ WHITE, BC MCDERMOTT, PJ EVANS, DR KRAUSE, GS AF NEUMAR, RW DEGRACIA, DJ WHITE, BC MCDERMOTT, PJ EVANS, DR KRAUSE, GS TI EUKARYOTIC INITIATION-FACTOR 4E DEGRADATION DURING BRAIN ISCHEMIA SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE CEREBRAL ISCHEMIA; PROTEIN DEGRADATION; CALPAIN; TRANSLATION INITIATION FACTOR ID CAP-BINDING-PROTEIN; TRANSIENT FOREBRAIN ISCHEMIA; DELAYED NEURONAL DEATH; MESSENGER-RNA; HEAT-SHOCK; RAT-BRAIN; CEREBRAL-ISCHEMIA; HIPPOCAMPUS; PHOSPHORYLATION; TRANSLATION AB Suppression of protein synthesis in the brain following an ischemic insult has been thought to occur because of inhibition of translation initiation. All eukaryotic mRNAs, with the exception of heat-shock transcripts, require the activity of eukaryotic initiation factor (eIf) 4E for formation of the translation initiation complex, and eIF-4E availability is rate-limiting. The response of brain eIF-4E concentration and phosphorylation following decapitation ischemia was studied in rat brain homogenates after electrophoresis and western blotting with antibodies against eIF-4E and phosphoserine, respectively. There was no change in level of eIF-4E after 5 min of ischemia (p = 0.82 vs. time 0), but it had decreased 32 (p = 0.01) and 57% (p = 0.006) after 10 and 20 min of ischemia, respectively. There was no loss of serine phosphorylation on eIF-4E beyond signal loss observed due to degradation of the protein itself (p = 0.31). In vitro exposure of eIF-4E to activated mu-calpain resulted in a 50% loss in 10 min of eIF-4E on western blots. If active eIF-4E is required for translation of its own mRNA, degradation of this protein during ischemia, possibly by activated mu-calpain, could be a direct mechanism of irreversible neuronal injury, and the rate of proteolysis of eIF-4E could place an upper time limit on the maximal duration of global brain ischemia compatible with neurologic recovery. C1 WAYNE STATE UNIV,SCH MED,DEPT EMERGENCY MED,DETROIT,MI 48201. WAYNE STATE UNIV,SCH MED,DEPT BIOCHEM,DETROIT,MI 48201. MED UNIV S CAROLINA,DEPT MED,DIV CARDIOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. NR 34 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1995 VL 65 IS 3 BP 1391 EP 1394 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA RQ571 UT WOS:A1995RQ57100053 PM 7643117 ER PT J AU YONG, WH CHOU, D UEKI, K HARSH, GR VONDEIMLING, A GUSELLA, JF MOHRENWEISER, HW LOUIS, DN AF YONG, WH CHOU, D UEKI, K HARSH, GR VONDEIMLING, A GUSELLA, JF MOHRENWEISER, HW LOUIS, DN TI CHROMOSOME-19Q DELETIONS IN HUMAN GLIOMAS OVERLAP TELOMERIC TO D19S219 AND MAY TARGET A 425 KB REGION CENTROMERIC TO D19S112 SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE CHROMOSOME 19; GLIOMA; LOSS OF HETEROZYGOSITY; OLIGODENDROGLIOMA; TUMOR SUPPRESSOR GENE, ERCC2, POLYMORPHISM ID MYOTONIC-DYSTROPHY REGION; TUMOR SUPPRESSOR; GENE; ASSOCIATION; CLONING; SEGMENT; REPEAT AB Chromosome 19q harbors a tumor suppressor gene that is involved in astrocytoma, oligodendroglioma and mixed glioma tumorigenesis. We had previously mapped this gene to an approximately 5 megabase region of chromosome 19q13.2-13.3 between APOC2 and HRC. To narrow the location of this tumor suppressor further, we studied 138 gliomas for loss of allelic heterozygosity at six microsatellite polymorphisms between APOC2 and HRC, including a newly described polymorphism in the ERCC2 gene. Allelic loss occurred in 48 gliomas (35%), including 25 of 41 oligodendroglial tumors (61%). Four cases had proximal breakpoints within the APOC2-HRC region, two telomeric to ERCC2 and two telomeric to D19S219. In addition, one of the latter tumors had an interstitial deletion between D19S219 and D19S112, a distance of only 425 kilobases surrounding the DM (myotonic dystrophy) gene. These findings suggest that the glioma tumor suppressor on chromosome 19q maps to 19q13.3, telomeric to D19S219 and perhaps centromeric to D19S112. The data exclude a number of candidate genes from 19q13.2-13.3, including a putative phosphatase gene and the DNA repair/metabolism genes ERCCl, ERCC2 and probably LIG1. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,LIVERMORE,CA. UNIV HOSP BONN,INST NEUROPATHOL,BONN,GERMANY. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [CA57683, T32-CA90216] NR 34 TC 37 Z9 37 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 1995 VL 54 IS 5 BP 622 EP 626 DI 10.1097/00005072-199509000-00002 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA RU105 UT WOS:A1995RU10500002 PM 7666049 ER PT J AU PAHL, JJ MAZZIOTTA, JC BARTZOKIS, G CUMMINGS, J ALTSCHULER, L MINTZ, J MARDER, SR PHELPS, ME AF PAHL, JJ MAZZIOTTA, JC BARTZOKIS, G CUMMINGS, J ALTSCHULER, L MINTZ, J MARDER, SR PHELPS, ME TI POSITRON-EMISSION TOMOGRAPHY IN TARDIVE-DYSKINESIA SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CEREBRAL GLUCOSE-UTILIZATION; SUPERIOR CERVICAL-GANGLION; COMPUTED-TOMOGRAPHY; ELECTRICAL-STIMULATION; HUNTINGTONS-DISEASE; BASAL GANGLIA; SCHIZOPHRENIA; METABOLISM; RAT; ACTIVATION AB Cerebral glucose metabolic rates were determined in normal control subjects (n = 26) and schizophrenic patients with tardive dyskinesia (n = 14). Globus pallidus and primary motor cortex (precentral gyrus) metabolic values divided by those of the cerebral hemispheres were significantly increased in the patient group. A similar metabolic pattern has not been reported for schizophrenic patients without tardive dyskinesia, and the abnormalities were demonstrated despite the normal appearance of the basal ganglia on X-ray CT. The findings differed markedly from the reduced metabolic rates of the basal ganglia previously identified in other choreiform disorders, including Huntington's and Wilson's diseases. The findings suggest that tardive dyskinesia is characterized by increased pallidal synaptic activity resulting from either altered striatopallidal input or increased pallidal interneuron firing. C1 UNIV OKLAHOMA,HLTH SCI CTR,DEPT PSYCHIAT,OKLAHOMA CITY,OK 73190. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,NUCL MED LAB,LOS ANGELES,CA 90024. RI Bartzokis, George/K-2409-2013 FU NIMH NIH HHS [R01 MH3791-AC03-76-SF0012]; NINDS NIH HHS [P01 NS15654] NR 60 TC 12 Z9 13 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1995 VL 7 IS 4 BP 457 EP 465 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TC116 UT WOS:A1995TC11600003 PM 8555748 ER PT J AU SULTZER, DL MAHLER, ME MANDELKERN, MA CUMMINGS, JL VANGORP, WG HINKIN, CH BERISFORD, MA AF SULTZER, DL MAHLER, ME MANDELKERN, MA CUMMINGS, JL VANGORP, WG HINKIN, CH BERISFORD, MA TI THE RELATIONSHIP BETWEEN PSYCHIATRIC-SYMPTOMS AND REGIONAL CORTICAL METABOLISM IN ALZHEIMERS-DISEASE SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; FRONTAL-LOBE; GLUCOSE-METABOLISM; PRIMARY DEMENTIA; MAJOR DEPRESSION; RATING-SCALE; DELUSIONS; BEHAVIOR; HYPOMETABOLISM; PSYCHOSIS AB Cognitive and noncognitive psychiatric symptoms we-re systematically evaluated in 21 patients with Alzheimer's disease by using the Neurobehavioral Rating Scale. Regional cerebral metabolic activity was measured in each patient by [F-18]fluorodeoxyglucose PET. Significant correlations emerged between global cortical metabolic activity and the Agitation/Disinhibition factor score, Cognition factor scare, and total score. Relationships between noncognitive symptoms and metabolic activity were regionally specific, with significant correlations between Agitation/Disinhibition factor score and metabolism in the frontal and temporal lobes, between Psychosis factor score and metabolism in the frontal lobe, and between Anxiety/Depression factor score and metabolism in the parietal lobe. These results suggest that psychiatric symptoms are fundamental expressions of the cortical dysfunction of Alzheimer's disease. C1 W LOS ANGELES VET AFFAIRS MED CTR,NUCL MED SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP SULTZER, DL (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,11301 WILSHIRE BLVD,BLDG 256,LOS ANGELES,CA 90073, USA. FU NIA NIH HHS [AG10123]; NIMH NIH HHS [MH00910] NR 66 TC 142 Z9 142 U1 2 U2 5 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1995 VL 7 IS 4 BP 476 EP 484 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TC116 UT WOS:A1995TC11600006 PM 8555751 ER PT J AU MIGUEL, EC STEIN, MC RAUCH, SL OSULLIVAN, RL STERN, TA JENIKE, MA AF MIGUEL, EC STEIN, MC RAUCH, SL OSULLIVAN, RL STERN, TA JENIKE, MA TI OBSESSIVE-COMPULSIVE DISORDER IN PATIENTS WITH MULTIPLE-SCLEROSIS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Note AB The authors present 3 cases of comorbid obsessive-compulsive disorder and multiple sclerosis and consider whether this comorbidity may reflect common pathophysiologic mechanisms rather than coincidence. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,OCD CLIN & RES UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT NEUROL,MS UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV SAO PAULO,SCH MED,DEPT PSYCHIAT,BR-05508 SAO PAULO,BRAZIL. RI Miguel, Euripedes/B-2871-2008 NR 16 TC 13 Z9 14 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1995 VL 7 IS 4 BP 507 EP 510 PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA TC116 UT WOS:A1995TC11600011 PM 8555756 ER PT J AU TAKAHASHI, T NOWAKOWSKI, RS CAVINESS, VS AF TAKAHASHI, T NOWAKOWSKI, RS CAVINESS, VS TI THE CELL-CYCLE OF THE PSEUDOSTRATIFIED VENTRICULAR EPITHELIUM OF THE EMBRYONIC MURINE CEREBRAL WALL SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CELL CYCLE; PROLIFERATION; NEURONOGENESIS; MOUSE; CEREBRUM; VENTRICULAR ZONE; NEOCORTEX ID STEM-CELLS; VISUAL-CORTEX; MATRIX CELLS; MOUSE; ZONE; BRAIN; TIME; PROLIFERATION; HISTOGENESIS; GENERATION AB Neurons destined for the cerebral neocortex are formed in the pseudostratified ventricular epithelium (PVE) lining the ventricular cavity of the developing cerebral wall. The present study, based upon cumulative S-phase labeling with bromodeoxyuridine, is an analysis of cell cycle parameters of the PVE. It is undertaken in the dorsomedial cerebral wall of mouse embryos from the eleventh to the seventeenth gestational day (E11-E17, day of conception = E0) corresponding to the complete period of neuronogenesis. The growth fraction (fraction of cells in the population which is proliferating) is virtually 1.0 from E11 through E16. The length of the cell cycle increases from 8.1 to 18.4 hr, which corresponds to a sequence of 11 integer cell cycles over the course of neuronal cytogenesis in mice. The increase in the length of the cell cycle is due essentially to a fourfold increase in the length of G1 phase which is the only phase of the cell cycle which varies systematically. Thus, the G1 phase is most likely to be the phase of the cell cycle which is modulated by extrinsically and intrinsically acting mechanisms involved in the regulation of neuronal cytogenesis. C1 KEIO UNIV,SCH MED,DEPT PEDIAT,TOKYO 160,JAPAN. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT NEUROSCI & CELL BIOL,PISCATAWAY,NJ 08854. RP TAKAHASHI, T (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,25 FRUIT ST,BOSTON,MA 02114, USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS28061, NS12005] NR 60 TC 429 Z9 437 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1995 VL 15 IS 9 BP 6046 EP 6057 PG 12 WC Neurosciences SC Neurosciences & Neurology GA RU108 UT WOS:A1995RU10800018 PM 7666188 ER PT J AU TAKAHASHI, T NOWAKOWSKI, RS CAVINESS, VS AF TAKAHASHI, T NOWAKOWSKI, RS CAVINESS, VS TI EARLY ONTOGENY OF THE SECONDARY PROLIFERATIVE POPULATION OF THE EMBRYONIC MURINE CEREBRAL WALL SO JOURNAL OF NEUROSCIENCE LA English DT Article DE CEREBRAL HISTOGENESIS; MOUSE; CELL CYCLE; PROLIFERATION; GLIOGENESIS; SUBVENTRICULAR ZONE; VENTRICULAR ZONE ID RADIAL GLIAL-CELLS; RHESUS-MONKEY; SUBVENTRICULAR ZONE; NEURONAL MIGRATION; GERMINAL MATRICES; VENTRICULAR ZONE; PRECURSOR CELLS; MAMMALIAN BRAIN; VISUAL-CORTEX; RAT CEREBRUM AB The present report is an analysis of the proliferative behavior of the secondary proliferative population (SPP) of the dorsomedial region of the embryonic mouse cerebral wall. It is based upon experiments undertaken on embryonic days 14-16 (E14-E16) and exploits methods in which proliferative cells are labeled in S phase with either or both bromodeoxyuridine and tritiated thymidine. The SPP, which arises from the PVE by E13, is principally the progenitor population to the neuroglial population of the mature neocortex and subjacent cerebral wall. By the end of E14 the SPP comes to be distributed diffusely from the outer margin of the ventricular zone throughout subventricular zone and intermediate zone. The length of the cell cycle of the SPP is constant at approximately 15 hr throughout this interval; thus, this population undergoes 1.6 cell cycles/24 hr or 3.2 cycles in the course of the 48 hr period, E14-E16. Over this 48 hr period, the SPP increases from 11% to 35% of the total proliferative population of the dorsomedial cerebral wall. The absolute size of the SPP increases nearly sixfold. With these values taken together it may be estimated that approximately 87% of postmitotic cells of the SPP reenter S phase after each cell division in this interval which means that only approximately 13% of the proliferative population exits the cycle. These findings illustrate the massive expansion of the SPP antecedent to the explosive diffusion of glial cells through the neocortex and subjacent cerebral wall as neuronal migration comes to completion and neocortical growth and differentiation accelerate. C1 KEIO UNIV, SCH MED, DEPT PEDIAT, TOKYO 160, JAPAN. UNIV MED & DENT NEW JERSEY, ROBERT WOOD JOHNSON MED SCH, DEPT NEUROSCI & CELL BIOL, PISCATAWAY, NJ 08854 USA. RP TAKAHASHI, T (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT NEUROL, 25 FRUIT ST, BOSTON, MA 02114 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS12005, NS28061] NR 83 TC 158 Z9 162 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 SEP PY 1995 VL 15 IS 9 BP 6058 EP 6068 PG 11 WC Neurosciences SC Neurosciences & Neurology GA RU108 UT WOS:A1995RU10800019 PM 7666189 ER PT J AU SANDROCK, AW GOODEARL, ADJ YIN, QW CHANG, D FISCHBACH, GD AF SANDROCK, AW GOODEARL, ADJ YIN, QW CHANG, D FISCHBACH, GD TI ARIA IS CONCENTRATED IN NERVE-TERMINALS AT NEUROMUSCULAR-JUNCTIONS AND AT OTHER SYNAPSES SO JOURNAL OF NEUROSCIENCE LA English DT Article DE SYNAPSE FORMATION; NEUROMUSCULAR JUNCTION; DEVELOPMENT; ACH RECEPTOR; NEU DIFFERENTIATION FACTOR (NDF); HEREGULIN (HER); GLIAL GROWTH FACTOR (GGF); NEUREGULIN; TROPHIC FACTOR ID ACETYLCHOLINE-RECEPTOR SYNTHESIS; ORIGINAL SYNAPTIC SITES; EPSILON-SUBUNIT GENE; ADULT MUSCLE-FIBERS; REGENERATING MUSCLE; CHICK MYOTUBES; MESSENGER-RNA; RAT MUSCLE; EXPRESSION; CELLS AB Skeletal muscle ACh receptors (AChRs) accumulate at neuromuscular junctions (nmjs) at least partly because of the selective induction of AChR subunit genes in subsynaptic myotube nuclei by the motor nerve terminal. Additionally, mammalian AChRs undergo a postnatal change in subunit composition from embryonic (alpha(2) beta gamma delta) to adult (alpha(2) beta epsilon delta) forms, a switch that also depends on innervation. ARIA, a protein purified from chicken brains based on its ability to induce AChR synthesis in primary chick muscle cells, is a strong candidate for being the molecule responsible for these early developmental events. ARIA mRNA has been detected in embryonic motor neurons during synapse formation, and the gene continues to be expressed postnatally. In this report, we provide evidence that ARIA-like immunoreactivity is concentrated in rat motor nerve terminals from early postnatal ages, and that it can be detected in motor neurons in E18 embryos. ARIA is also detectable in axons within colchicine-treated sciatic nerves, suggesting that the protein in the nerve terminal has been transported from the cell body. ARIA mRNA is present in, but not restricted to, cholinergic neurons. Likewise, we report here that ARIA-like immunoreactivity is present in some noncholinergic central synapses. We also present evidence that isoforms of ARIA are differentially distributed among functionally distinct classes of neurons. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. AMGEN INC,THOUSAND OAKS,CA 91320. FU NINDS NIH HHS [NS18458, NS01580-02] NR 53 TC 82 Z9 82 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP PY 1995 VL 15 IS 9 BP 6124 EP 6136 PG 13 WC Neurosciences SC Neurosciences & Neurology GA RU108 UT WOS:A1995RU10800026 PM 7666195 ER PT J AU MOVASSAGHI, K ALTOBELLI, DE ZHOU, H AF MOVASSAGHI, K ALTOBELLI, DE ZHOU, H TI FRONTONASAL SUTURE EXPANSION IN THE RABBIT USING TITANIUM SCREWS SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID RIGID ENDOSSEOUS IMPLANTS; BONE; DISTRACTION; ANCHORAGE; GROWTH; SKULL AB Purpose: This study investigated the ability to use titanium screws to provide stable skeletal points in the growing craniofacial region of the rabbit for suture expansion, These screws provided sites for direct application of external forces to alter growth and anatomic form. Material and Methods. Twenty-one rabbits (30 days old) were divided into three groups: control (n = 9), experimental (n = 9), acid sham (n = 3), Four four-holed AO/ASIF commercially pure titanium craniofacial plates were contoured into an L-shape with a 90 degrees angle at the midpoint. The plates were placed bilaterally in the frontal and nasal bone sites and secured with 2.0-mm diameter, 4-mm long, commercially pure titanium screws in both the sham and experimental groups, After 4 weeks of healing, a spring mechanism with a distraction force of 55 g was activated between ipsilateral plates and across the frontonasal sutures bilaterally in the experimental group for 5 weeks. No force was applied between the plates in the sham group. A preliminary evaluation of the bone-implant interface and the changes in the sutures was done histologically. Morphologic changes were measured using cephalometric radiographs and direct anatomic measurements. Results: The experimental group showed a significant increase in growth across the frontonasal suture in comparison with the sham group (P < .05). In addition, an increase in the length of the nasal and frontal bones in the expanded group was observed in comparison with the control and sham groups (P < .05). Histologically, a mixture of woven and lamellar bone was seen in the suture region and lamellar bone was seen in the screw-bone interface. Conclusion: This study indicates that titanium screws in the developing rabbit skull can provide stable sites for the direct application of external forces, producing secondary changes in skeletal mrophology. This laboratory model provides a useful system for the further study of growth modification using such external mechanical forces. C1 MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. HARVARD UNIV,SCH DENT MED,FACIAL ENGN & MORPHOL LAB,CAMBRIDGE,MA 02138. NR 29 TC 23 Z9 24 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 1995 VL 53 IS 9 BP 1033 EP 1042 DI 10.1016/0278-2391(95)90121-3 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA RR642 UT WOS:A1995RR64200013 PM 7643273 ER PT J AU SAVARESE, JJ BRINKEN, BW ZALESKE, DJ AF SAVARESE, JJ BRINKEN, BW ZALESKE, DJ TI EPIPHYSEAL REPLACEMENT IN A MURINE MODEL SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE DEVELOPMENT; EPIPHYSIS; GROWTH PLATE; JOINT; TRANSPLANTATION AB Epiphyseal replacement was performed via knee transplantation using donor tissue of different developmental times in a murine model. The performance of syngeneic donor tissue in a resection defect in 4-day-old mice of the same inbred strain was assessed over 2 weeks for cell viability, tritiated thymidine incorporation, and ability to attract a host blood supply, and at 2 months, with the existence of a joint and growth. Although there was variability within experimental groups, the syngeneic transplant was able to survive pending vascular invasion from the host. Growth occurred, although it never equaled normal growth. One possible approach to the difficult problem of joint reconstruction in the immature skeleton is to divide the endeavor into two parts: develop models of syngeneic joint transplantation in inbred strains of animals to assess the various problems that would occur were this tissue available and develop models of joint ''synthesis'' with autogeneic chondrocytes. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED,BOSTON,MA 02114. FU NIAMS NIH HHS [AR39380] NR 0 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD SEP-OCT PY 1995 VL 15 IS 5 BP 682 EP 690 PG 9 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA RP869 UT WOS:A1995RP86900026 PM 7593586 ER PT J AU TORCHILIN, VP TRUBETSKOY, VS WHITEMAN, KR CALICETI, P FERRUTI, P VERONESE, FM AF TORCHILIN, VP TRUBETSKOY, VS WHITEMAN, KR CALICETI, P FERRUTI, P VERONESE, FM TI NEW SYNTHETIC AMPHIPHILIC POLYMERS FOR STERIC PROTECTION OF LIPOSOMES IN-VIVO SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID CIRCULATION TIME; INVIVO; IMMUNOLIPOSOMES; STABILITY; CLEARANCE AB Carboxy group-terminated synthetic polymers-branched poly(ethylene glycol), poly(acryloyl morpholine), and poly(vinylpyrrolidone)-were made amphiphilic by derivatization with phosphatidyl ethanolamine via the terminal carboxy group and then incorporated into lecithin-cholesterol liposomes prepared by the detergent dialysis method. Following the biodistribution of liposomes in mice, all three polymers were shown to be effective steric protectors for liposomes and were able to sharply increase liposome circulation times in a concentration-dependent manner. The accumulation of liposomes in the liver decreases. The effects observed are similar to those found for liposomes modified with linear poly(ethylene glycol). At low polymer concentration, amphiphilic branched poly(ethylene glycol) seems to be the most effective liposome protector, most probably, because at the same molar content of anchoring groups, each attachment point carries two polymeric chains and doubles the quantity of liposome-grafted polymer comparing to linear poly(ethylene glycol). C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV PADUA,DEPT PHARMACEUT SCI,I-35131 PADUA,ITALY. UNIV BRESCIA,DEPT CHEM & PHYS MAT,I-25123 BRESCIA,ITALY. RP TORCHILIN, VP (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR IMAGING & PHARMACEUT RES,149 13TH ST,BOSTON,MA 02129, USA. NR 34 TC 106 Z9 108 U1 1 U2 18 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD SEP PY 1995 VL 84 IS 9 BP 1049 EP 1053 DI 10.1002/jps.2600840904 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA RU659 UT WOS:A1995RU65900003 PM 8537880 ER PT J AU CHEN, G WAXMAN, DJ AF CHEN, G WAXMAN, DJ TI COMPLETE REVERSAL BY THALIBLASTINE OF 490-FOLD ADRIAMYCIN RESISTANCE IN MULTIDRUG-RESISTANT (MDR) HUMAN BREAST-CANCER CELLS - EVIDENCE THAT MULTIPLE BIOCHEMICAL-CHANGES IN MDR CELLS NEED NOT CORRESPOND TO MULTIPLE FUNCTIONAL DETERMINANTS FOR DRUG-RESISTANCE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; PROTEIN KINASE-C; P-GLYCOPROTEIN; TUMOR-CELLS; CARCINOMA-CELLS; CYTO-TOXICITY; BUTHIONINE SULFOXIMINE; CONFERS RESISTANCE; ANTICANCER DRUGS; GENE-EXPRESSION AB The emergence of drug resistance is a major obstacle to effective cancer chemotherapy. The identification of novel agents that serve as selective, potent and nontoxic modulators of drug resistance is thus an important goal for improving the success of cancer treatment. Thaliblastine (TBL), a plant alkaloid and P-glycoprotein (P-gp) inhibitor, is presently shown to fully reverse 490-fold resistance to Adriamycin (AdR) in a multidrug-resistant (MDR) human breast cancer cell line (MCF/AdR) that overexpresses P-gp, whereas the same treatment had no effect on AdR cytotoxicity in the drug-sensitive parental MCF-7 cells. Mechanistic studies showed that this striking resistance reversal was achieved without alteration of cellular levels of glutathione and without inhibition of glutathione S-transferase, glutathione peroxidase or P450 reductase by TBL, each of which is significantly altered in MCF/AdR cells, and each of which has been proposed to contribute to AdR resistance in this MDR line. Rather, resistance reversal by TBL can be entirely explained by this drug's capacity to restore the intracellular accumulation of AdR in the resistant cells. These results establish that MDR associated with P-gp overexpression can be fully reversed by the potent P-gp inhibitor TBL. They further indicate that although changes in multiple drug-metabolizing enzymes may accompany the development of MDR, these multiple biochemical alterations need not correspond to multiple functional determinants for drug resistance. C1 BOSTON UNIV,DEPT BIOL,DIV CELL & MOLEC BIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA49248] NR 60 TC 15 Z9 15 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1995 VL 274 IS 3 BP 1271 EP 1277 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA RV893 UT WOS:A1995RV89300033 PM 7562498 ER PT J AU DCRUZ, DP WISNIESKI, JJ ASHERSON, RA KHAMASHTA, MA HUGHES, GRV AF DCRUZ, DP WISNIESKI, JJ ASHERSON, RA KHAMASHTA, MA HUGHES, GRV TI AUTOANTIBODIES IN SYSTEMIC LUPUS-ERYTHEMATOSUS AND URTICARIAL VASCULITIS SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE ANTIENDOTHELIAL CELL ANTIBODIES; ANTI-C1Q ANTIBODIES; HYPOCOMPLEMENTEMIA; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES ID COLLAGEN-LIKE REGION; RHEUMATIC DISEASES; ANTIBODIES; C1Q; MARKER; IGG; NEPHRITIS; CLQ AB Objective. Urticarial vasculitis (UV) is both a primary disorder and a cutaneous vasculitic manifestation in patients with connective tissue diseases. We examined the prevalence of autoantibodies to vascular endothelial cells (aECA) and anti-Clq antibodies in patients with UV. Methods. ELISA were used to detect aECA and anti-Clq autoantibodies, and we tested for correlation with UV in 4 patient groups: healthy controls, patients with systemic lupus erythematosus (SLE) with and without UV, patients with primary systemic vasculitides with UV, and patients with hypocomplementemic urticarial vasculitis syndrome (HUVS). Results. aECA were detected in 82% of patients with SLE with UV and 70% of patients with HUVS. In contrast, aECA were found in 32% of patients with SLE without UV and 14% of patients with primary UV. Anti-Clq antibodies were present in all patients with HUVS, but in < 20% in the other 3 groups. Antineutrophil cytoplasmic antibodies were detected in only one patient. Conclusion. Although the development of UV is likely to be multifactorial, the high prevalence of aECA in HUVS and SLE with UV suggests that this antibody is associated with vasculitis and may have a role in the pathogenesis of UV in these patients. C1 ST THOMAS HOSP,RAYNE INST,LUPUS ARTHRITIS RES UNIT,LONDON SE1 7EH,ENGLAND. US DEPT VET AFFAIRS,CLEVELAND,OH. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NR 23 TC 18 Z9 18 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD SEP PY 1995 VL 22 IS 9 BP 1669 EP 1673 PG 5 WC Rheumatology SC Rheumatology GA RT927 UT WOS:A1995RT92700013 PM 8523343 ER PT J AU SPENCER, T BIEDERMAN, J HARDING, M WILENS, T FARAONE, S AF SPENCER, T BIEDERMAN, J HARDING, M WILENS, T FARAONE, S TI THE RELATIONSHIP BETWEEN TIC DISORDERS AND TOURETTES-SYNDROME REVISITED SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE TOURETTES SYNDROME; TIC DISORDERS; COMORBIDITY; NEUROPSYCHOLOGY ID DEFICIT HYPERACTIVITY DISORDER; LEARNING-DISABILITIES; DEPRESSIVE-DISORDERS; CHILDREN; RISK; PERFORMANCE; RELATIVES; CHILDHOOD AB Objective: The relationship between Tourette's syndrome (TS) and chronic tic disorder is of great clinical acid scientific importance because of uncertainties in both prognosis and pharmacotherapeutic strategies. One approach to evaluating the relationship between TS and chronic ties is to examine whether they share similar neuropsychological and psychiatric correlates. Method: Children with TS (n = 32) and children with chronic ties (n = 39) were ascertained from an unselected sample of the children referred for psychopharmacological treatment and examined using standardized diagnostic assessments and testing procedures. Results: Children with TS and those with chronic ties were similar to each other and different from controls in clinical correlates that included psychiatric comorbidity, as well as school, neuropsychological, and psychosocial impairments. Patients with TS also had higher rates of obsessive-compulsive disorder, oppositional defiant disorder, and simple phobia than did patients with chronic tic disorder. Conclusions: These findings indicate that TS and chronic tic disorder are part of the same disease entity, with TS being a more severe form of tic disorder. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP SPENCER, T (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,FRUIT ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [K20 MH01169-01] NR 42 TC 49 Z9 49 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1995 VL 34 IS 9 BP 1133 EP 1139 DI 10.1097/00004583-199509000-00009 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RR323 UT WOS:A1995RR32300009 PM 7559306 ER PT J AU BIEDERMAN, J THISTED, R GREENHILL, L RYAN, N AF BIEDERMAN, J THISTED, R GREENHILL, L RYAN, N TI RESOLVED - CARDIAC-ARRHYTHMIAS MAKE DESIPRAMINE AN UNACCEPTABLE CHOICE IN CHILDREN - NEGATIVE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Discussion ID ADOLESCENTS; ADD C1 HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CHICAGO,DEPT STAT,CHICAGO,IL 60637. NEW YORK STATE PSYCHIAT INST & HOSP,DIV CHILD & ADOLESCENT PSYCHIAT,NEW YORK,NY. WESTERN PSYCHIAT INST & CLIN,DEPT PSYCHIAT,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. RI Thisted, Ronald/B-1985-2008 NR 9 TC 0 Z9 0 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1995 VL 34 IS 9 BP 1241 EP 1245 DI 10.1097/00004583-199509000-00024 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RR323 UT WOS:A1995RR32300024 ER PT J AU BIEDERMAN, J AF BIEDERMAN, J TI RESOLVED - CARDIAC-ARRHYTHMIAS MAKE DESIPRAMINE AN UNACCEPTABLE CHOICE IN CHILDREN - NEGATIVE REBUTTAL SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Discussion C1 HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CHICAGO,DEPT STAT,CHICAGO,IL 60637. NEW YORK STATE PSYCHIAT INST & HOSP,DIV CHILD & ADOLESCENT PSYCHIAT,NEW YORK,NY. WESTERN PSYCHIAT INST & CLIN,DEPT PSYCHIAT,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 1995 VL 34 IS 9 BP 1246 EP 1248 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA RR323 UT WOS:A1995RR32300026 ER PT J AU OHTANI, H STRAUSS, HW SOUTHERN, JF TAMATANI, T MIYASAKA, M SEKIGUCHI, M ISOBE, M AF OHTANI, H STRAUSS, HW SOUTHERN, JF TAMATANI, T MIYASAKA, M SEKIGUCHI, M ISOBE, M TI INTERCELLULAR-ADHESION MOLECULE-1 INDUCTION - A SENSITIVE AND QUANTITATIVE MARKER FOR CARDIAC ALLOGRAFT-REJECTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID HISTOCOMPATIBILITY COMPLEX ANTIGENS; NONINVASIVE DETECTION; KIDNEY ALLOGRAFTS; T-CELLS; CLASS-I; INDIUM-111-LABELED LYMPHOCYTES; LFA-1-DEPENDENT ADHESION; MONOCLONAL-ANTIBODIES; ENDOTHELIAL-CELLS; INTERFERON-GAMMA AB Objectives. Rats with abdominal heterotopic heart trans plants were studied to determine whether cardiac allograft rejection could be assessed by immunoscintigraphy targeting intercellular adhesion molecule-1 (ICAM-1), which was induced on allografted organ cells in association with rejection. Background. It is important to detect early rejection before development of myocyte necrosis. Although a variety of methods for the detection of cardiac rejection have been investigated, histologic inspection of biopsied samples is still used routinely for clinical diagnosis of rejection. Methods. DA rat (RT-1a) hearts were transplanted into PVG rats (RT-1(c)). Immunohistologic examination of the allografts demonstrated that ICAM-1 induction on vascular endothelial cells was observed as early as 4 days after transplantation in this combination. Thirty nine allografted rats and seven isografted rats were studied. One day after injection of 100 mu Ci of In-111-labeled anti-ICAM-1 monoclonal antibody (1A29), planar images were obtained. Results. Rejecting allografts showed increased radiotracer uptake and could be identified on the images as early as 5 days after transplantation. In contrast, nonrejecting cardiac allografts and isografts did not show specific uptake. Mildly rejecting allografts, with mononuclear cell infiltration but without significant myocyte necrosis, could be scintigraphically identified, and the level of radiotracer uptake reflected the histologic severity of rejection. Accumulation of In-111-labeled monoclonal antibody of isotype-matched irrelevant specificity was not detected in the rejecting allografts. Conclusions. These data indicate that ICAM-1 induction can be assessed quantitatively by radioimmunoscintigraphy. Radioimmunoscintigraphy is a sensitive method for early detection and assessment of cardiac allograft rejection. C1 SHINSHU UNIV,SCH MED,DEPT INTERNAL MED 1,MATSUMOTO,NAGANO 390,JAPAN. FUKUSHIMA MED COLL,DEPT INTERNAL MED 1,FUKUSHIMA,JAPAN. MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. JAPAN TOBACCO INC,PHARMACEUT BASIC RES LABS,KANAGAWA,JAPAN. OSAKA UNIV,BIOMED RES CTR,DEPT BIOREGULAT,OSAKA,JAPAN. NR 45 TC 13 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 1995 VL 26 IS 3 BP 793 EP 799 DI 10.1016/0735-1097(95)00222-P PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA RR070 UT WOS:A1995RR07000031 PM 7642875 ER PT J AU MCDOUGAL, WS STAMPFER, DS KIRLEY, S BENNETT, PM LIN, CW AF MCDOUGAL, WS STAMPFER, DS KIRLEY, S BENNETT, PM LIN, CW TI INTESTINAL AMMONIUM TRANSPORT BY AMMONIUM AND HYDROGEN-EXCHANGE SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID URINARY-DIVERSION; SEGMENTS; INHIBITION; ABSORPTION; VESICLES; ACIDOSIS; COLON; NH4+ AB BACKGROUND: Ionized ammonia (NH3) transport in the intestine has not been previously established as a mechanism of acidosis in urinary intestinal diversion or hepatic failure. STUDY DESIGN: The purpose of this study was to establish that ionized transport of ammonium (NH4) occurs in the intestine and to characterize the mechanism of its transport using the methodology of brush border membrane vesicles and acridine orange fluorescence. RESULTS: An NH4/H exchange was demonstrated and found to be the dominant mechanism causing a pH change when NH4 is transported across the lumenal membrane. Ionized NH4 transport was demonstrated to occur against an NH3 concentration gradient. The K-m was 1.02 mmol and the V-max was 247 U/sec. The Hill coefficient was 0.97, indicating a single port. Ammonium hydrogen exchange could be inhibited by amiloride but not by bumetanide, Sodium, potassium or chloride, or both, did not effect the NH4/H exchanger. CONCLUSIONS: This study establishes that ionized NH4 transport occurs across the small intestine brush border in exchange for a hydrogen ion. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,GRB 1102,BOSTON,MA 02114, USA. NR 22 TC 1 Z9 1 U1 1 U2 1 PU AMER COLL SURGEONS PI CHICAGO PA 54 EAST ERIE ST, CHICAGO, IL 60611 SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD SEP PY 1995 VL 181 IS 3 BP A241 EP A248 PG 8 WC Surgery SC Surgery GA RT205 UT WOS:A1995RT20500008 ER PT J AU CAREY, M AF CAREY, M TI DIABETES GUIDELINES, OUTCOMES, AND COST-EFFECTIVENESS STUDY - A PROTOCOL, PROTOTYPE, AND PARADIGM SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material ID DIETETICS PRACTITIONERS; NUTRITION CARE; OUTPATIENTS; MELLITUS RP CAREY, M (reprint author), MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,101 MERRIMAC ST,BOSTON,MA 02114, USA. NR 20 TC 6 Z9 6 U1 0 U2 1 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 1995 VL 95 IS 9 BP 976 EP 978 DI 10.1016/S0002-8223(95)00267-7 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RU459 UT WOS:A1995RU45900004 PM 7657911 ER PT J AU MCGEHEE, MM JOHNSON, EQ RASMUSSEN, HM SAHYOUN, N LYNCH, MM CAREY, M AF MCGEHEE, MM JOHNSON, EQ RASMUSSEN, HM SAHYOUN, N LYNCH, MM CAREY, M TI BENEFITS AND COSTS OF MEDICAL NUTRITION THERAPY BY REGISTERED DIETITIANS FOR PATIENTS WITH HYPERCHOLESTEROLEMIA SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID SERUM-CHOLESTEROL; DISEASE; EFFICACY; DIET AB The Massachusetts Dietetic Association implemented a statewide retrospective quality assurance audit to determine the effectiveness and cost of medical nutrition therapy in patients with hypercholesterolemia (>5.20 mmol/L). Hypercholesterolemia is a major risk factor for coronary artery disease (CAD). Data were collected at 23 sites from 285 outpatients seen by a registered dietitian for a minimum of two visits. Patients taking lipid-lowering medications were excluded. Of the 285 patients, 108 (38%) were men and 177 (62%) were women. The mean age was 51.4 years (range=22 to 79 years). Results showed that the mean reduction in serum cholesterol level was 8.6%, which translates to a decrease of approximately 17.2% in risk of CAD. Forty-five percent of the total population showed an 11% or greater reduction in serum cholesterol levels. Reduction;in serum cholesterol levels correlated with increased time spent with a dietitian (r=.188, P<.001). The mean cost for nutrition intervention with a dietitian was $163 (a mean of four visits). In contrast, the estimated annual cost of treatment for patients with hypercholesterolemia using drug therapy is $1,450. A 1993 report calculated the annual cost of treating heart disease in the United States to be $80 billion. Medical nutrition therapy should be considered the initial, effective, and low-cost approach in the management of patients with mild to moderate hypercholesterolemia. C1 MASSACHUSETTS GEN HOSP,PATIENT FOOD & CLIN NUTR SERV,BOSTON,MA 02114. CAMBRIDGE HOSP,AMBULATORY NUTR SERV,CAMBRIDGE,MA 02139. TUFTS UNIV,JEAN MAYER HUMAN NUTR RES CTR AGING,USDA,BOSTON,MA 02111. MGH,INST HLTH PROFESS,GRAD PROGRAM DIETET,BOSTON,MA. RI Sahyoun, Nadine/G-2608-2011 NR 18 TC 31 Z9 31 U1 1 U2 3 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD SEP PY 1995 VL 95 IS 9 BP 1041 EP 1043 DI 10.1016/S0002-8223(95)00288-X PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA RU459 UT WOS:A1995RU45900018 PM 7657908 ER PT J AU BRAR, P SCHULTZ, J MATTHEWS, R BEAL, M AF BRAR, P SCHULTZ, J MATTHEWS, R BEAL, M TI THE FREE-RADICAL SPIN TRAP N-TERT-BUTYL-ALPHA (2-SULFOPHENYL)-NITRONE (S-PBN) REDUCES MALONATE INDUCED NEURONAL CELL INJURY IN RATS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1995 VL 43 IS 9 BP SA8 EP SA8 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RT908 UT WOS:A1995RT90800060 ER PT J AU ROCHE, VML WELSH, CH AF ROCHE, VML WELSH, CH TI LACK OF RELATIONSHIP BETWEEN AGE, ADMISSION MEDICATIONS AND OUTCOME IN THE INTENSIVE-CARE UNIT SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 UNIV COLORADO,HLTH SCI CTR,DENVER VA MED CTR,DENVER,CO. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1995 VL 43 IS 9 BP SA76 EP SA76 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA RT908 UT WOS:A1995RT90800332 ER PT J AU BARNETT, GO AF BARNETT, GO TI INFORMATION TECHNOLOGY AND MEDICAL-EDUCATION SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Editorial Material RP BARNETT, GO (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,50 STANDORD ST,5TH FLOOR,BOSTON,MA 02114, USA. NR 0 TC 10 Z9 12 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 1995 VL 2 IS 5 BP 285 EP 291 PG 7 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 RV581 UT WOS:A1995RV58100002 PM 7496877 ER PT J AU BRETON, S BROWN, D AF BRETON, S BROWN, D TI THE LYSOSOMAL GLYCOPROTEIN LGP120 IS SELECTIVELY INSERTED INTO THE BASOLATERAL MEMBRANE OF KIDNEY COLLECTING DUCT (CD) TYPE-B INTERCALATED CELLS (IC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,RENAL UNIT,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 305 EP 305 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600012 ER PT J AU EMMONS, C AF EMMONS, C TI TRANSPORT CHARACTERISTICS OF THE APICAL ANION-EXCHANGER OF CCD BETA-INTERCALATED CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 308 EP 308 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600021 ER PT J AU NAGAMI, GT WARECH, EM AF NAGAMI, GT WARECH, EM TI EFFECT OF ACID LOADING ON ANGIOTENSIN-II-INDUCED CHANGES IN AMMONIA PRODUCTION BY THE MOUSE PROXIMAL TUBULE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,NEPHROL SECT,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,NEPHROL SECT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 311 EP 311 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600036 ER PT J AU NAGAMI, GT WARECH, EM AF NAGAMI, GT WARECH, EM TI EFFECT OF ANGIOTENSIN-II ON AMMONIA PRODUCTION BY MOUSE S3 PROXIMAL TUBULE SEGMENTS - DIFFERENTIAL BASOLATERAL AND LUMINAL RESPONSES SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,MED SERV,NEPHROL SECT,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,NEPHROL SECT,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 311 EP 311 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600035 ER PT J AU JUNG, FF TANG, SS HAVERAN, L SABOLIC, I VERBAVATZ, JM BROWN, D INGELFINGER, JR AF JUNG, FF TANG, SS HAVERAN, L SABOLIC, I VERBAVATZ, JM BROWN, D INGELFINGER, JR TI LOW-SALT AND OUABAIN DOWN-REGULATE AQUAPORIN-1 EXPRESSION IN RAT PROXIMAL TUBULE CELLS (IRPTC) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 324 EP 324 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600085 ER PT J AU KATSURA, T AUSIELLO, DA BROWN, D AF KATSURA, T AUSIELLO, DA BROWN, D TI DIRECT DEMONSTRATION OF AQUAPORIN-2 (AQP2) RECYCLING IN CYCLOHEXIMIDE-TREATED, STABLY TRANSFECTED LLC-PK1 CELLS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 324 EP 324 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600087 ER PT J AU BROOKER, DR SMITH, PR WEISER, PC MCNULTY, KA MACKLER, SA KLEYMAN, TR AF BROOKER, DR SMITH, PR WEISER, PC MCNULTY, KA MACKLER, SA KLEYMAN, TR TI CLONING OF MOUSE EPITHELIAL NA CHANNEL AND LOCALIZATION IN THE URINARY-BLADDER SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV PENN,COLL MED,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,COLL MED,DEPT PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. SYRACUSE UNIV,DEPT BIOL,SYRACUSE,NY 13244. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 333 EP 333 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600123 ER PT J AU KLEYMAN, TR LIN, CM MCNULTY, KA GOMEZ, LM WORRELL, RT EATON, DC LING, BN AF KLEYMAN, TR LIN, CM MCNULTY, KA GOMEZ, LM WORRELL, RT EATON, DC LING, BN TI EXPRESSION OF THE CYSTIC-FIBROSIS PHENOTYPE IN A RENAL AMPHIBIAN EPITHELIAL-CELL LINE (A6) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV PENN,DEPT MED,DIV RENAL,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. EMORY UNIV,ATLANTA,GA 30322. VET AFFAIRS MED CTR,ATLANTA,GA 30033. NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 342 EP 342 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600159 ER PT J AU PRAT, AG REISIN, IL AUSIELLO, DA CANTIELLO, HF AF PRAT, AG REISIN, IL AUSIELLO, DA CANTIELLO, HF TI CELLULAR ATP RELEASE BY THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 349 EP 349 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600187 ER PT J AU ALPER, SL STUARTTILLEY, AK BROWN, D AF ALPER, SL STUARTTILLEY, AK BROWN, D TI IMMUNOLOCALIZATION OF AE2 ANION-EXCHANGER IN RAT-KIDNEY SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. NR 1 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 371 EP 371 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600276 ER PT J AU ALPER, SL STUARTTILLEY, AK YANNOUKAKOS, D BROWN, D AF ALPER, SL STUARTTILLEY, AK YANNOUKAKOS, D BROWN, D TI AE3 ANION-EXCHANGER IMMUNOLOCALIZATION IN RODENT KIDNEY - EVIDENCE FOR APICAL AND BASOLATERAL ISOFORMS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BETH ISRAEL HOSP,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02215. NR 0 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 372 EP 372 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600277 ER PT J AU BRETON, S BROWN, D AF BRETON, S BROWN, D TI COLD TREATMENT DISRUPTS THE MICROTUBULE NETWORK OF KIDNEY EPITHELIAL-CELLS - EFFECT ON PROTEIN TRAFFICKING IN PROXIMAL (PT) AND COLLECTING TUBULES (CT) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 373 EP 373 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600282 ER PT J AU FATH, KR BURGESS, DR HAMMOND, TG AF FATH, KR BURGESS, DR HAMMOND, TG TI CYTOSKELETAL MOTOR DEPENDENCE OF RAT RENAL ENDOSOMAL FUSION - MEDIATION BY DYNEIN BUT NOT MYOSIN-I SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. UNIV WISCONSIN,MADISON,WI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 374 EP 374 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600288 ER PT J AU HAMMOND, TG VERROUST, PJ AF HAMMOND, TG VERROUST, PJ TI THE INTERNALIZATION SEQUENCE OF RENAL CORTICAL SCAVENGER PATHWAY RECEPTORS EFFECT FUSION OF MEMBRANES IN WHICH THEY RESIDE VIA DIRECT INTERACTIONS WITH H+-ATPASE SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. HOP TENON,INSERM,U64,F-75970 PARIS,FRANCE. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 375 EP 375 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600289 ER PT J AU PEDRINI, MT LAU, J LEVEY, AS CHALMERS, TC WANG, PH AF PEDRINI, MT LAU, J LEVEY, AS CHALMERS, TC WANG, PH TI EFFECT OF DIETARY-PROTEIN RESTRICTION ON THE PROGRESSION OF NONDIABETIC RENAL-DISEASE - METAANALYSIS SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. UNIV CALIF IRVINE,IRVINE,CA 92717. NR 2 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1995 VL 6 IS 3 SI SI BP 399 EP 399 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA RX686 UT WOS:A1995RX68600386 ER EF