FN Thomson Reuters Web of Science™ VR 1.0 PT J AU TALAL, N AF TALAL, N TI HISTORICAL OVERVIEW OF SJOGRENS-SYNDROME SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 4th Breton Workshop on Autoimmunity CY APR 14-16, 1994 CL BREST, FRANCE SP CONSEIL REG BRETAGNE, CONSEIL GEN FINISTERE, FRENCH NAVY, UNIV BRETAGNE OCCIDENTALE C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CLIN IMMUNOL SECT,SAN ANTONIO,TX 78284. NR 8 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD NOV-DEC PY 1994 VL 12 SU 11 BP S3 EP S4 PG 2 WC Rheumatology SC Rheumatology GA QN123 UT WOS:A1994QN12300002 PM 7768047 ER PT J AU SILVER, MT LIEBERMAN, EH THIBAULT, GE AF SILVER, MT LIEBERMAN, EH THIBAULT, GE TI REFRACTORY HYPOXEMIA IN INFERIOR MYOCARDIAL-INFARCTION FROM RIGHT-TO-LEFT SHUNTING THROUGH A PATENT FORAMEN OVALE - A CASE-REPORT AND REVIEW OF THE LITERATURE SO CLINICAL CARDIOLOGY LA English DT Note DE HYPOXEMIA; MYOCARDIAL INFARCTION; PATENT FORAMEN OVALE; SHUNT; RIGHT VENTRICLE ID RIGHT VENTRICULAR INFARCTION; OCCLUSION; HYPOXIA; PATIENT; THERAPY AB Right ventricular (RV) infarction is a well-recognized complication of some acute inferior myocardial infarctions. Recently, there have been numerous case reports of RV infarctions complicated by severe refractory hypoxemia secondary to right-to-left shunting through a patent foramen ovale. An additional case missed by transthoracic echocardiography and cardiac catheterization is reported and the English literature on the subject is reviewed. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. BROCKTON W ROXBURY VET ADM MED CTR,DEPT MED,BOSTON,MA. RP SILVER, MT (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 15 TC 14 Z9 15 U1 0 U2 2 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD NOV PY 1994 VL 17 IS 11 BP 627 EP 630 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP559 UT WOS:A1994PP55900011 PM 7834939 ER PT J AU LOPESVIRELLA, MF VIRELLA, G AF LOPESVIRELLA, MF VIRELLA, G TI ATHEROSCLEROSIS AND AUTOIMMUNITY SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; CIRCULATING IMMUNE-COMPLEXES; MONOCYTE-DERIVED MACROPHAGES; HUMAN-ENDOTHELIAL-CELLS; SMOOTH-MUSCLE CELLS; CHOLESTERYL ESTER ACCUMULATION; SYSTEMIC LUPUS-ERYTHEMATOSUS; POLYMORPHONUCLEAR LEUKOCYTES; MONOCLONAL-ANTIBODIES; VASCULAR DISEASES AB The possible involvement of immunological mechanisms in the pathogenesis of atherosclerosis has been suggested intermittently since the early 1970s. Both humoral and cellular mechanisms have been proposed to participate in the onset and/or progression of atheromatous lesions, but the theories postulating the involvement of autoantibodies and immune complexes have met with considerable experimental support. Modified lipoproteins, particularly different forms of oxidized LDL, have been reported to elicit humoral immune responses in both experimental animals and humans. Oxidized LDL has been demonstrated in atheromatous lesions, anti-oxidized LDL antibodies have been detected in circulation and in atheromatous plaques, and immune complexes formed with LDL and anti-LDL have been isolated from the serum of patients with manifestations of atherosclerosis. In addition, in vitro-formed LDL-IC and IC isolated from patients have been demonstrated to cause intracellular accumulation of cholesteryl esters (CE) in human macrophages and fibroblasts. The accumulation of CE in macrophages exposed to LDL-IC is unique to this type of IC and is associated with a paradoxical overexpression of the native LDL receptor and with increase synthesis and release of interleukin 1 and TNF-alpha. The release of these cytokines in the subendothelial space may have a significant role in promoting the interaction of endothelial cells with mononuclear cells, causing endothelial cell damage directly or indirectly, and also in inducing smooth muscle cell proliferation. Thus, several lines of evidence suggest that humoral autoimmunity may play a significant role in the pathogenesis of atherosclerosis. (C) 1994 Academic Press, Inc. C1 MED UNIV S CAROLINA,DEPT MED,DIV METAB ENDOCRINOL & NUTR,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT MICROBIOL & IMMUNOL,CHARLESTON,SC 29425. RP LOPESVIRELLA, MF (reprint author), RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,109 BEE ST,CHARLESTON,SC 29403, USA. NR 97 TC 49 Z9 52 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD NOV PY 1994 VL 73 IS 2 BP 155 EP 167 DI 10.1006/clin.1994.1184 PG 13 WC Immunology; Pathology SC Immunology; Pathology GA PN333 UT WOS:A1994PN33300001 PM 7923923 ER PT J AU PEGUES, DA CARR, DB HOPKINS, CC AF PEGUES, DA CARR, DB HOPKINS, CC TI INFECTIOUS COMPLICATIONS ASSOCIATED WITH TEMPORARY EPIDURAL CATHETERS SO CLINICAL INFECTIOUS DISEASES LA English DT Note ID PAIN AB To identify cases of deep-tissue or local infection associated with temporary epidural catheters, we reviewed medical records from 1980 through 1992 and prospectively followed up patients with temporary epidural catheters from January 1993 through June 1993 who were hospitalized at a large, tertiary referral hospital. We identified seven cases of temporary epidural catheter-associated infection, including three cases of deep-tissue infection (paraspinal muscle abscess, epidural abscess, and meningitis) and four cases of local infection. The infections were diagnosed 2 days to 22 days following insertion of the epidural catheter. Staphylococcus aureus was isolated in four (57%) of the cases. All seven patients were treated with removal of the catheter and antimicrobial therapy; three patients also required surgical drainage for management of deep-tissue infection. Our findings emphasize the importance of daily inspection and prompt removal of temporary epidural catheters if infection is suspected. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,CTR PAIN,BOSTON,MA 02114. RP PEGUES, DA (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,INFECT DIS UNIT,GRAY 5,32 FRUIT ST,BOSTON,MA 02114, USA. NR 9 TC 35 Z9 36 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 NOV PY 1994 VL 19 IS 5 BP 970 EP 972 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PT713 UT WOS:A1994PT71300031 PM 7893892 ER PT J AU BAKER, AS OKADA, AA JOHNSON, RP AF BAKER, AS OKADA, AA JOHNSON, RP TI ENDOGENOUS ENDOPHTHALMITIS SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. TOKYO MED COLL HOSP,DEPT OPHTHALMOL,DEPT UVEITIS,TOKYO,JAPAN. RP BAKER, AS (reprint author), MASSACHUSETTS EYE & EAR INFIRM,INFECT DIS SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 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 NOV PY 1994 VL 19 IS 5 BP 982 EP 982 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PT713 UT WOS:A1994PT71300042 PM 7893902 ER PT J AU JASTY, M BRAGDON, C JIRANEK, W CHANDLER, H MALONEY, W HARRIS, WH AF JASTY, M BRAGDON, C JIRANEK, W CHANDLER, H MALONEY, W HARRIS, WH TI ETIOLOGY OF OSTEOLYSIS AROUND POROUS-COATED CEMENTLESS TOTAL HIP ARTHROPLASTIES SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID LOCALIZED BONE-RESORPTION; COMPONENTS; FAILURE; LYSIS; FEMUR AB The prosthetic components and tissues retrieved from 12 hips with osteolysis in association with well-fixed cementless porous-coated total hip prostheses (5 Porous Coated Anatomic, 6 Harris-Galante Porous, and 1 Omniflex) were examined using a variety specific techniques including electron microscopy, standard histology, immunohistochemistry, and particle identification. The patients were young and active. Extensive osteolysis developed in all 12 femurs and 3 acetabula between 36 and 84 months after arthroplasty (mean, 63 months). All of the polyethylene liners were noted to be worn substantially (mean volumetric wear, 1140 +/- 810 mm(3)). The wear was unrelated to the head diameter in this small number of cases. In all 12 cases, the articulating surfaces were wear polished and contained numerous fine multidirectional scratches, suggesting 3-body abrasive wear mechanisms in addition to adhesive wear liberating very small (micron to submicron) wear particles. In 4 cases, surface delamination and flaking of polyethylene were also found, suggesting fatigue wear liberating larger wear particles. Nine of 10 cobalt alloy heads showed numerous fine scratches with sharp edges presumably from 3-body abrasive wear. Corrosion and fretting at the femoral head-neck junction in 5 cases, burnishing of the femoral stem against bone in 4 cases, and metal staining of tissues opposite the porous coatings in 7 cases provided evidence for the liberation of fine metal particles from outside the articulation. Histologic and immunohistochemical studies of tissue in the regions of osteolysis in all cases showed numerous focal aggregates of KP1 antibody positive activated macrophages containing large amounts of submicron intracellular particles of polyethylene (presumably related to the 3-body abrasive wear polishing) and giant cells within a fibrous stroma. In 5 cases, some of the macrophages also contained submicron metal particles but smaller in numbers. T lymphocytes, plasma cells, and mast cells that might indicate hypersensitivity were found in 4 of the 12 cases (33%), and none of the cases had B lymphocytes. These data suggest that abrasive wear at the articulation leads to the liberation of abundant fine particulate wear debris of polyethylene into the tissues around cementless prostheses. Small amounts of particulate metal debris are also liberated from corrosion and fretting of the metal components and can contribute to accelerated 3-body abrasive wear at the articulation. The abundant fine polymeric debris, however, is the most common feature in cases with uncemented components of different alloys and designs, and is the most likely agent for the production of osteolysis by giving rise to an aggressive, foreign-body granulomatous tissue reaction. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP JASTY, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114, USA. NR 24 TC 87 Z9 90 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 1994 IS 308 BP 111 EP 126 PG 16 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PQ777 UT WOS:A1994PQ77700018 PM 7955673 ER PT J AU KOMIYA, S TSUZUKI, K MANGHAM, DC SUGIYAMA, M INOUE, A AF KOMIYA, S TSUZUKI, K MANGHAM, DC SUGIYAMA, M INOUE, A TI OXYGEN SCAVENGERS IN SIMPLE BONE-CYSTS SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SUPEROXIDE-DISMUTASE; FREE-RADICALS; NEUTROPHILS; MACROPHAGE; ACTIVATION AB Simple bone cyst is a fluid-filled, cystic lesion that occurs in the metaphysis of the long bones of children and adolescents. The chemical characteristics of the cyst fluid of the simple bone cyst are similar to those of serum, The existence of the cyst fluid itself may be an obstacle to cyst healing, and, in part, this may be because the cyst fluid contains bone destructive factors. Oxygen-free radicals, which are cytotoxic and cause connective tissue damage, are known to be generated under ischemic conditions. Blockage to the drainage of interstitial fluid within the metaphysis has been suggested as the possible primary cause of simple bone cyst, thus causing an ischemic state in which free radicals are generated. The precise measurement of free radical levels is difficult to obtain because of their extremely short half-lives. High levels of oxygen-free radicals induce high levels of oxygen scavengers Locally to protect cells from the harmful effects of the free radicals. Therefore, the activity of the oxygen scavengers, superoxide dismutase and catalase, was measured in the cyst fluid of 9 cases of simple bone cyst as an indicator of high oxygen-free radical content in the cyst. Serum from the patients with simple bone cyst and joint fluid from patients with osteoarthritis were used for comparison with the intracystic levels of oxygen scavengers. Superoxide dismutase activity was directly measured at room temperature using an electron spin resonance spin-trapping technique with 5,5'-dimethyl-1-pyrroline-N-oxide as a trapping agent. Catalase was measured with a spectrophotometer. Superoxide dismutase activity in cyst fluid was 15-fold greater than in the patients' serum, and catalase activity was 5.5-fold higher. These values were also significantly higher than those in joint fluid from osteoarthritis patients. These results suggest that high activity of oxygen radicals may exist in cyst fluid of simple bone cyst and may contribute to bone destruction. C1 KURUME UNIV,FAC MED,DEPT ORTHOPAED SURG,KURUME,FUKUOKA 830,JAPAN. KURUME UNIV,FAC MED,DEPT CHEM,KURUME,FUKUOKA 830,JAPAN. MASSACHUSETTS GEN HOSP,ORTHOPAED RES LABS,BOSTON,MA. NR 23 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 1994 IS 308 BP 199 EP 206 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PQ777 UT WOS:A1994PQ77700029 PM 7955684 ER PT J AU ZHANEL, GG CRAIG, WA AF ZHANEL, GG CRAIG, WA TI PHARMACOKINETIC CONTRIBUTIONS TO POSTANTIBIOTIC EFFECTS - FOCUS ON AMINOGLYCOSIDES SO CLINICAL PHARMACOKINETICS LA English DT Review ID BETA-LACTAM ANTIBIOTICS; GRAM-NEGATIVE BACTERIA; EXPERIMENTAL PSEUDOMONAS ENDOCARDITIS; KILLING-CURVE METHOD; ESCHERICHIA-COLI; ENTEROCOCCUS-FAECALIS; STAPHYLOCOCCUS-AUREUS; SUBINHIBITORY CONCENTRATIONS; ANTIMICROBIAL ACTIVITY; INVITRO ACTIVITY AB The postantibiotic effect (PAE) refers to a period of time after complete removal of an antimicrobial during which there is no growth of the target organism. The PAE appears to be a feature of most antimicrobial agents and has been documented with a variety of common bacterial pathogens. Various factors influence the presence or duration of the PAE including the type of organism, type of antimicrobial, concentration of antimicrobial, duration of antimicrobial exposure, antimicrobial combinations, and inoculum and medium used. beta-Lactams demonstrate a PAE against Gram-positive cocci, but produce only a short PAE with Gram-negative bacilli. Antimicrobial agents that inhibit RNA or protein synthesis have a PAE against Gram-positive cocci and Gram-negative bacilli. In vivo studies of aminoglycosides suggest that area under the plasma concentration-time curve is the pharmacokinetic parameter that best correlates with clinical efficacy. This is thought to be due to the concentration-dependent killing and PAE possessed by these antimicrobials. Animal and human studies have reported that once-daily administration of aminoglycoside is as effective as, or more effective than, and possibly less toxic than traditional multiple daily administration. C1 UNIV MANITOBA, FAC MED, DEPT MED MICROBIOL, WINNIPEG, MB, CANADA. UNIV MANITOBA, FAC PHARM, WINNIPEG R3T 2N2, MB, CANADA. UNIV WISCONSIN, WILLIAM S MIDDLETON MEM VET HOSP, MADISON, WI USA. UNIV WISCONSIN, FAC MED, MADISON, WI USA. NR 123 TC 39 Z9 48 U1 1 U2 3 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD NOV PY 1994 VL 27 IS 5 BP 377 EP 392 DI 10.2165/00003088-199427050-00005 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PQ553 UT WOS:A1994PQ55300005 PM 7851055 ER PT J AU NORMAN, DC YOSHIKAWA, TT AF NORMAN, DC YOSHIKAWA, TT TI INFECTIONS OF THE BONE, JOINT, AND BURSA SO CLINICS IN GERIATRIC MEDICINE LA English DT Article AB Septic arthritis caused by Neisseria gonorrhoeae is an infection almost exclusively of patients younger than 40(21,39); rarely is the infection reported in elderly patients.(14,16) Therefore, this discussion on septic arthritis in the geriatric population is on nongonococcal septic arthritis. When several studies of nongonococcal septic arthritis (hereafter referred to as septic arthritis) in adults are analyzed, approximately 40% of these cases occur in patients aged 60 years and older.(26,38) This high proportion of joint infection with increased age appears to have occurred primarily during the recent antibiotic era.(35) Moreover, an increasing number of reports on septic arthritis in older patients have appeared in the literature during the past decade.(9,24,31,34,51,60) Mortality caused by septic arthritis in the general adult population is approximately 10%.(26) In contrast, elderly patients with joint infections experience death rates ranging from 19% to 33%.(24,31,51) Morbidity or complications associated with septic arthritis (e.g., osteomyelitis, loss of joint function, osteoarthritis, duration of immobility) also appear to increase with age.(9,24,31,51) C1 DEPT VET AFAIRS,OFF GERIATR & EXTENDED CARE 114,WASHINGTON,DC 20420. W LOS ANGELES DEPT VET AFFAIRS MED CTR,LOS ANGELES,CA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0749-0690 J9 CLIN GERIATR MED JI Clin. Geriatr. Med. PD NOV PY 1994 VL 10 IS 4 BP 703 EP 718 PG 16 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA PU744 UT WOS:A1994PU74400011 PM 7850698 ER PT J AU NEW, AS TRESTMAN, RL SIEVER, LJ AF NEW, AS TRESTMAN, RL SIEVER, LJ TI THE PHARMACOTHERAPY OF BORDERLINE PERSONALITY-DISORDER SO CNS DRUGS LA English DT Article ID IMPULSIVE AGGRESSIVE-BEHAVIOR; DSM-III; DIAGNOSTIC INTERVIEW; DOUBLE-BLIND; HALOPERIDOL; FLUOXETINE; PLACEBO; PHENELZINE; EFFICACY; LITHIUM AB Pharmacotherapy is used increasingly as a helpful adjunct to psychotherapeutic interventions in the treatment of borderline personality disorder. Clinical trials have been performed to investigate drug treatment of the 3 symptom clusters associated with borderline personality disorder - impulsivity, affective lability and psychotic-like symptoms. Although no single agent ameliorates all the symptoms of this diagnosis, and patients vary considerably in their response to medication, pharmacological strategies for each symptom can be delineated. Impulsivity and aggression can be treated with selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), lithium, beta-adrenoceptor blockers or antipsychotics. Affective symptomology has also been found to respond to MAOIs, SSRIs and lithium. Interestingly, patients with borderline personality disorder do not seem to respond to tricyclic antidepressants. As would be expected, antipsychotics are the most effective medications for the treatment of the psychotic symptoms of borderline personality disorder. Various techniques to improve compliance and enhance the treatment alliance with the patient can be suggested, including patient education about the role of the pharmacologist (and therapist) in treatment and about the nature of agents prescribed. In addition, if possible, patients should be allowed to play an active part in the selection of drugs. C1 BRONX VET AFFAIRS MED CTR,DEPT PSYCHIAT,NEW YORK,NY. MT SINAI MED CTR,NEW YORK,NY 10029. RP NEW, AS (reprint author), WESTERN PSYCHIAT INST & CLIN,RM 1175,3811 OHARA ST,PITTSBURGH,PA 15243, USA. NR 56 TC 4 Z9 4 U1 1 U2 3 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD NOV PY 1994 VL 2 IS 5 BP 347 EP 354 DI 10.2165/00023210-199402050-00003 PG 8 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA PQ781 UT WOS:A1994PQ78100003 ER PT J AU CHU, JL SHIELDS, SR NETLAND, PA AF CHU, JL SHIELDS, SR NETLAND, PA TI ENHANCEMENT OF FILTRATION SURGERY WITH CYTOSINE-ARABINOSIDE AND REVERSAL OF TOXICITY WITH 2'-DEOXYCYTIDINE SO CURRENT EYE RESEARCH LA English DT Article DE CYTOSINE ARABINOSIDE; CYTARABINE; 2'-DEOXYCYTIDINE; GLAUCOMA FILTRATION SURGERY; ANTIMETABOLITE ID GLAUCOMA FILTERING SURGERY; MITOMYCIN-C; FIBROBLAST PROLIFERATION; CAPSULE FIBROBLASTS; TOPICAL MITOMYCIN; SUB-CONJUNCTIVAL; ARA-C; 5-FLUOROURACIL; TRABECULECTOMY; FLUOROURACIL AB Antifibrosis agents have improved the success of glaucoma filtration surgery, although undesired side effects are not readily reversible and may present a major limitation in the use of these agents. Our purpose was to study the efficacy of cytosine arabinoside (Ara-C) as an adjunctive antimetabolite in glaucoma surgery in the rabbit, and reversal of toxicity due to this agent with the competitive inhibitor 2'-deoxycytidine. Posterior lip sclerectomy was performed in rabbit eyes treated with 15 mg subconjunctival Ara-C daily for 7 d then every other day for 7 d. Mean intraocular pressure was lower in eyes treated with Ara-C compared with controls at all time points following filtration surgery. On the 10th postoperative day, the mean intraocular pressure of control eyes (25.0 +/- 1.9 mm Hg) had returned to baseline levels, whereas the intraocular pressure of eyes treated with Ara-C was significantly lower (16.0 +/- 1.7 mm Hg) (P < 0.01). Bleb survival was also prolonged in the Ara-C-treated eyes. The major ocular side effect of Ara-C was corneal toxicity, with epithelial defects in 40% of eyes after 8 daily injections of 15 mg Ara-C. Reversal of toxicity was enhanced with 2'-deoxycytidine, with complete resolution of epithelial toxicity after 6.5 +/- 1.7 d following daily topical 10% 2'-deoxycytidine compared with 12.7 +/- 0.58 for control (P < 0.002). These results demonstate that postoperative subconjunctival injection of Ara-C results in improved bleb function after filtration surgery in the rabbit. Recovery from corneal epithelial toxicity due to Ara-C is markedly enhanced with the competitive inhibitor 2'-deoxycytidine. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 28 TC 2 Z9 2 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 NOV PY 1994 VL 13 IS 11 BP 839 EP 843 DI 10.3109/02713689409025140 PG 5 WC Ophthalmology SC Ophthalmology GA PQ859 UT WOS:A1994PQ85900009 PM 7851120 ER PT J AU BHAN, AK MIZOGUCHI, E MIZOGUCHI, A AF BHAN, AK MIZOGUCHI, E MIZOGUCHI, A TI NEW MODELS OF CHRONIC INTESTINAL INFLAMMATION SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article AB Gene-targeting technology in embryonic stem cells has allowed creation of animals transgenic or mutant for a number of molecules. The presence of spontaneous chronic intestinal inflammation in mice mutant for interleukin-2, interleukin-10, and T-cell receptor genes has provided new models of chronic intestinal inflammation. By crossing mice mutant for different genes with each other, it is possible to generate mice deficient for a group of specific cytokines, adhesion molecules, or lymphocyte subsets. These models will not only help clarify the role of factors considered important in the pathogenesis of chronic intestinal inflammation, but they also permit precise dissection of mucosal immune responses and may help develop new therapeutic approaches to human inflammatory bowel disease. RP BHAN, AK (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,IMMUNOPATHOL UNIT,COX-5,BOSTON,MA 02114, USA. NR 0 TC 21 Z9 21 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 1994 VL 10 IS 6 BP 633 EP 638 DI 10.1097/00001574-199411000-00011 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PP744 UT WOS:A1994PP74400011 ER PT J AU HOTAMISLIGIL, GS SPIEGELMAN, BM AF HOTAMISLIGIL, GS SPIEGELMAN, BM TI TUMOR-NECROSIS-FACTOR-ALPHA - A KEY COMPONENT OF THE OBESITY-DIABETES LINK SO DIABETES LA English DT Review ID INSULIN-RECEPTOR SUBSTRATE-1; SIGNAL-REGULATED KINASES; PROTEIN MAP KINASE; TYROSINE PHOSPHORYLATION; MOLECULAR-CLONING; GLUCOSE-METABOLISM; HUMAN FIBROBLASTS; FACTOR ACTIVATE; TNF-RECEPTORS; CACHECTIN TNF AB Recent data have suggested a key role for tumor necrosis factor (TNF)-alpha in the insulin resistance of obesity and non-insulin-dependent diabetes mellitus (NIDDM). TNF-alpha expression is elevated in the adipose tissue of multiple experimental models of obesity. Neutralization of TNF-alpha in one of these models improves insulin sensitivity by increasing the activity of the insulin receptor tyrosine kinase, specifically in muscle and fat tissues. On a cellular level, TNF-alpha is a potent inhibitor of the insulin-stimulated tyrosine phosphorylations on the beta-chain of the insulin receptor and insulin receptor substrate-1, suggesting a defect at or near the tyrosine kinase activity of the insulin receptor. Given the clear link between obesity, insulin resistance, and diabetes, these results strongly suggest that TNF-alpha may play a crucial role in the systemic insulin resistance of NIDDM. This may allow for new treatments of disorders involving resistance to insulin. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. NR 97 TC 935 Z9 973 U1 1 U2 16 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1994 VL 43 IS 11 BP 1271 EP 1278 DI 10.2337/diabetes.43.11.1271 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN281 UT WOS:A1994PN28100001 PM 7926300 ER PT J AU JUANG, JH BONNERWEIR, S WU, YJ WEIR, GC AF JUANG, JH BONNERWEIR, S WU, YJ WEIR, GC TI BENEFICIAL INFLUENCE OF GLYCEMIC CONTROL UPON THE GROWTH AND FUNCTION OF TRANSPLANTED ISLETS SO DIABETES LA English DT Article ID STREPTOZOTOCIN-DIABETIC RATS; AUTOTRANSPLANTED PANCREATIC-ISLETS; OBESE-HYPERGLYCEMIC MICE; BETA-CELL MASS; DNA-REPLICATION; KIDNEY CAPSULE; B-CELL; GLUCOSE; EXOCRINE; EXPRESSION AB Syngeneic transplantation of 200 mouse islets under the kidney capsule usually fails to cure streptozocin-induced diabetes. We hypothesized that this number of islets, if engrafted in a normoglycemic environment, could expand their mass and improve their function to restore normoglycemia. Therefore, 200 freshly isolated mouse islets were transplanted under the capsule of each kidney of diabetic mice. Two weeks after transplantation, the recipients were normoglycemic, and one of the two grafts was removed. Removal of the graft was followed by transient hyperglycemia. At day 14 after graft removal, the beta-cell mass and insulin content of the remaining graft had increased 2.3- and 2.1-fold, respectively. At day 3 after graft removal, the replication rate of beta-cells increased threefold, and the mean individual beta-cell cross-sectional area, an indicator of cell size, was also increased. Perfusion of the kidney bearing the remaining graft showed biphasic insulin responses to high glucose and arginine 14 days after one graft removal. These data indicate that maintaining a period of near-normoglycemia after islet transplantation enhances the performance of an islet graft that would otherwise be expected to fail. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. RP JUANG, JH (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. RI Juang, Jyuhn-Huarng /C-2465-2011 FU NIDDK NIH HHS [DK 36836, DK 35449] NR 38 TC 87 Z9 87 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1994 VL 43 IS 11 BP 1334 EP 1339 DI 10.2337/diabetes.43.11.1334 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN281 UT WOS:A1994PN28100010 PM 7926308 ER PT J AU KUNISAKI, M BURSELL, SE UMEDA, F NAWATA, H KING, GL AF KUNISAKI, M BURSELL, SE UMEDA, F NAWATA, H KING, GL TI NORMALIZATION OF DIACYLGLYCEROL-PROTEIN KINASE-C ACTIVATION BY VITAMIN-E IN AORTA OF DIABETIC RATS AND CULTURED RAT SMOOTH-MUSCLE CELLS EXPOSED TO ELEVATED GLUCOSE-LEVELS SO DIABETES LA English DT Note ID ALPHA-TOCOPHEROL; COMPLICATIONS; INHIBITION; GLYCOSYLATION; PROLIFERATION; PATHOGENESIS; MEDIATION AB Hyperglycemia and diabetes have been shown to increase diacylglycerol (DAG) level and activate protein kinase C (PKC) activity in the vascular tissues, possibly altering vascular function. We have characterized the effects of D-alpha-tocopherol (vitamin E) on PKC activities and DAG levels in rat aortic smooth muscle cells (ASMCs) cultured with elevated glucose levels as well as in the vascular tissues obtained from control and diabetic rats. In ASMCs, the specific PKC activity from the membraneous fraction and total DAG level were increased by 31 +/- 4% (P < 0.05) and 50 +/- 7% (P < 0.05), respectively, when the glucose levels were changed from 5.5 to 22 mmol/l. The addition of D-alpha-tocopherol and another lipophilic antioxidant, probucol, prevented the glucose-stimulated increases in DAG level and PKC activity. By immunoblotting studies, D-alpha-tocopherol treatment was able to reduce the enhancement of PKC PII isoform in the membraneous fraction isolated from ASMCs. Comparing streptozotocin-induced diabetic rats with their nondiabetic controls, both membraneous-specific PKC activities and total cellular DAG levels were increased in aorta by 162% (P < 0.05) and 60% (P < 0.05), respectively. Intraperitoneal injection of D-alpha-tocopherol (40 mg/kg) every other day prevented the increases in membraneous-specific PKC activities and total DAG levels in parallel with a significant increase of D-alpha-tocopherol contents in the aorta and plasma. These findings have demonstrated that D-alpha-tocopherol can prevent the activation of PKC activities in the vascular cells and tissues induced by hyperglycemia by lowering DAG levels, possibly via its antioxidant effect. C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. KYUSHU UNIV,FAC MED,DEPT INTERNAL MED 3,FUKUOKA 812,JAPAN. FU NEI NIH HHS [EY-05110]; NIDDK NIH HHS [DK-36836] NR 30 TC 153 Z9 154 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1994 VL 43 IS 11 BP 1372 EP 1377 DI 10.2337/diabetes.43.11.1372 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN281 UT WOS:A1994PN28100016 PM 7926314 ER PT J AU ERSHLER, WB SUN, WH BINKLEY, N AF ERSHLER, WB SUN, WH BINKLEY, N TI THE ROLE OF INTERLEUKIN-6 IN CERTAIN AGE-RELATED DISEASES SO DRUGS & AGING LA English DT Review ID MYELOMA-CELL-GROWTH; ACUTE PHASE RESPONSE; ALZHEIMERS-DISEASE; MULTIPLE-MYELOMA; CYTOKINE EXPRESSION; SIGNAL TRANSDUCER; PRECURSOR PROTEIN; HODGKINS-DISEASE; BONE-RESORPTION; IL-6 AB Interleukin-6 (IL-6) is a pro-inflammatory cytokine with a wide range of functions. Perhaps the most important physiologically is its role as a mediator of the acute phase inflammatory response. Normally, there is little measurable IL-6 in the circulation, but levels increase abruptly to nanogram amounts during an inflammatory process. During aging, it has been proposed that the tight regulation of IL-6 gene expression becomes less effective and levels are measurable even when there is no evidence for inflammation. Several investigators have identified this cytokine as being involved in the pathogenesis of various disease processes and we have suggested that certain age-associated diseases are directly related. Among these are late-life lymphoma and myeloma, osteoporosis and possibly Alzheimer's disease. RP ERSHLER, WB (reprint author), UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,CTR GERIATR RES EDUC & CLIN,DEPT MED,MADISON,WI 53706, USA. FU NIA NIH HHS [AG00451, AG00213] NR 68 TC 64 Z9 64 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PD NOV PY 1994 VL 5 IS 5 BP 358 EP 365 PG 8 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA PQ371 UT WOS:A1994PQ37100005 PM 7833589 ER PT J AU TOSTESON, ANA WEINSTEIN, MC WITTENBERG, J BEGG, CB AF TOSTESON, ANA WEINSTEIN, MC WITTENBERG, J BEGG, CB TI ROC CURVE REGRESSION-ANALYSIS - THE USE OF ORDINAL REGRESSION-MODELS FOR DIAGNOSTIC-TEST ASSESSMENT SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 4th Japan/US Biostatistics Conference on the Study of Human Cancer CY NOV 09-11, 1993 CL TOKYO, JAPAN DE ROC CURVES; ORDINAL REGRESSION; SENSITIVITY; SPECIFICITY; DIAGNOSTIC TEST ASSESSMENT; RATING EXPERIMENT ID METHODOLOGY; AREA AB Diagnostic tests commonly are characterized by their true positive (sensitivity) and true negative (specificity) classification rates, which rely on a single decision threshold to classify a test result as positive. A more complete description of test accuracy is given by the receiver operating characteristic (ROC) curve, a graph of the false positive and true positive rates obtained as the decision threshold is varied. A generalized regression methodology, which uses a class of ordinal regression models to estimate smoothed ROC curves has been described. Data from a multi-institutional study comparing the accuracy of magnetic resonance (MR) imaging with computed tomography (CT) in detecting liver metastases, which are ideally suited for ROC regression analysis, are described. The general regression model is introduced and an estimate for the area under the ROC curve and its standard error using parameters of the ordinal regression model is given. An analysis of the liver data that highlights the utility of the methodology in parsimoniously adjusting comparisons for covariates is presented. C1 DARTMOUTH COLL SCH MED,DEPT MED & COMMUNITY & FAMILY MED,LEBANON,NH. HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,CAMBRIDGE,MA 02138. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,CAMBRIDGE,MA 02138. MEM SLOAN KETTERING CANC CTR,DEPT EPIDEMIOL & BIOSTAT,NEW YORK,NY 10021. FU NCI NIH HHS [I-CM-47564] NR 13 TC 18 Z9 18 U1 0 U2 4 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 NOV PY 1994 VL 102 SU 8 BP 73 EP 78 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PW221 UT WOS:A1994PW22100013 PM 7851336 ER PT J AU AURON, PE WEBB, AC AF AURON, PE WEBB, AC TI INTERLEUKIN-1 - A GENE-EXPRESSION SYSTEM REGULATED AT MULTIPLE LEVELS SO EUROPEAN CYTOKINE NETWORK LA English DT Review ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; HUMAN PROINTERLEUKIN-1-BETA GENE; IMMEDIATE EARLY GENES; TATA-BINDING PROTEIN; MESSENGER-RNA EXPRESSION; CTLA-4 COUNTER-RECEPTOR; TRANSCRIPTION FACTOR; HUMAN-MONOCYTES; DNA-BINDING C1 WELLESLEY COLL,DEPT BIOL SCI,WELLESLEY,MA 02181. RP AURON, PE (reprint author), HARVARD UNIV,SCH MED,DEPT PATHOL,CTR BLOOD RES,WARREN ALPERT BLDG,ROOM 154,200 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI27850]; NIAMS NIH HHS [AR03564] NR 161 TC 81 Z9 81 U1 0 U2 4 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD NOV-DEC PY 1994 VL 5 IS 6 BP 573 EP 592 PG 20 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA QG159 UT WOS:A1994QG15900007 PM 7727690 ER PT J AU CALVO, V WOOD, M GJERTSON, C VIK, T BIERER, BE AF CALVO, V WOOD, M GJERTSON, C VIK, T BIERER, BE TI ACTIVATION OF 70-KDA S6 KINASE, INDUCED BY THE CYTOKINES INTERLEUKIN-3 AND ERYTHROPOIETIN AND INHIBITED BY RAPAMYCIN, IS NOT AN ABSOLUTE REQUIREMENT FOR CELL-PROLIFERATION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE PROTEIN KINASES; CYTOKINES; RAPAMYCIN; PROLIFERATION ID PROTEIN-KINASE; LYMPHOCYTES-T; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; CYCLOSPORINE-A; DISTINCT MECHANISMS; MACROLIDES FK-506; FRIEND-VIRUS; RECEPTOR; STIMULATION AB The cytokines interleukin (IL)-3 and erythropoietin (EPO) are critical regulators of the proliferation and differentiation of cells of the hematopoietic system, but their intracellular mechanisms of action are not fully understood. Binding of IL-3 to the IL-3 receptor (IL-3R) and binding of EPO to the EPOR both induce changes in intracellular tyrosine and serine/threonine phosphorylation; the phosphorylation of a number of polypeptides appears to be a shared response upon cytokine stimulation. We have previously shown that binding of IL-2 to the IL-2R activates the 70-kDa (p70) 86 kinase, a serine/threonine kinase whose activity is regulated by serine/threonine phosphorylation; the immunosuppressant rapamycin inhibits IL-2-dependent proliferation and IL-2-triggered activation of p70 S6 kinase. We, therefore, sought to examine whether induction of p70 86 kinase activity is a conserved response upon cytokine triggering, and whether this activity is essential for cell proliferation. Proliferation of the IL-3-dependent pro-B cell line Ba/F3 transfected with the EPOR (Ba/F3-EPOR) can be supported by either IL-3 or EPO. In this cell line, both IL-3 and EPO induced p70 86 kinase activity; rapamycin inhibited both the IL-3 and EPO-induced activation of the 70-kDa S6 kinase as well as cellular proliferation. Thus: p70 S6 kinase activation appears to be a common intermediate triggered by the stimulation of IL-3, EPO, and IL-2 receptors. The Friend spleen focus-forming virus gp55 renders the EPOR constitutively active, and confers growth factor independence on cells expressing EPOR. Ba/F3-EPOR cotransfected with gp55 (Ba/F3-EpoRgp55) and the erythroleukemia cell line MEL, which also expresses both the EPOR and gp55, were analyzed. Rapamycin inhibited the activation of p70 S6 kinase in both cell lines. However, rapamycin inhibited proliferation of Ba/F3-EpoRgp55 but not of MEL cells despite inhibition of p70 86 kinase activity in both cells. Thus, p70 86 kinase activation is not an absolute requirement for cell proliferation. These results are discussed in relation to the role of the activation of the 70-kDa 86 kinase activation pathway in the regulation of cell cycle progression. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RI Calvo, Victor/L-5024-2014 OI Calvo, Victor/0000-0002-5913-7058 FU NIAID NIH HHS [AI32514] NR 51 TC 41 Z9 41 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 NOV PY 1994 VL 24 IS 11 BP 2664 EP 2671 DI 10.1002/eji.1830241115 PG 8 WC Immunology SC Immunology GA PT424 UT WOS:A1994PT42400015 PM 7957559 ER PT J AU RUSSELL, GJ PARKER, CM CEPEK, KL MANDELBROT, DA SOOD, A MIZOGUCHI, E EBERT, EC BRENNER, MB BHAN, AK AF RUSSELL, GJ PARKER, CM CEPEK, KL MANDELBROT, DA SOOD, A MIZOGUCHI, E EBERT, EC BRENNER, MB BHAN, AK TI DISTINCT STRUCTURAL AND FUNCTIONAL EPITOPES OF THE ALPHA(E)BETA(7) INTEGRIN SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE INTEGRINS; MUCOSAL LYMPHOCYTES; ADHESION; ALPHA(E)BETA(7) ID INTESTINAL INTRAEPITHELIAL LYMPHOCYTES; T-CELL RECEPTOR; MONOCLONAL-ANTIBODY HML-1; MAMMARY EPITHELIAL-CELLS; ADHESION RECEPTORS; CELIAC-DISEASE; FACTOR-BETA; EXPRESSION; ANTIGEN; GROWTH AB Intestinal intraepithelial lymphocytes (iIEL) are predominantly CD3(+), CD8(+) T lymphocytes located above or adjacent to the mucosal basement membrane. Although they are positioned to interact with intercellular luminal antigen or with enterocytes, the function of iIEL remains unknown. Most (>85%) of the iIEL express the alpha(E) beta(7) integrin which appears to be involved in the adhesion of lymphocytes to epithelial cells. We report the characterization of three monoclonal antibodies (mAb) termed alpha E7-1, alpha E7-2, and alpha E7-3, that react with the alpha(E) beta(7) integrin recognized by the previously described mAb HML-1 as demonstrated by identical sodium dodecyl sulfate - polyacrylamide gel electrophoresis mobility and charge. Flow cytometric analysis of antibody cross-blocking indicated that these mAb recognize distinct epitopes of alpha(E) beta(7). While all of the mAb were capable of blocking the adhesion of cultured iIEL to a breast epithelial cell line, only HML-1 and alpha E7-1 (which recognize an identical or closely related epitope) were co-stimulatory with suboptimal concentrations of atni-CD3 mAb in inducing proliferation of cultured iIEL. Thus, these mAb appear to recognize functionally distinct epitopes of alpha(E) beta(7) and will be useful to study relationships between the structure and function of this integrin. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,DIV MED SCI,BOSTON,MA 02115. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MED,NEW BRUNSWICK,NJ 08903. RP RUSSELL, GJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK33506, DK43351, KO8DK02010] NR 52 TC 43 Z9 44 U1 1 U2 1 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 NOV PY 1994 VL 24 IS 11 BP 2832 EP 2841 DI 10.1002/eji.1830241138 PG 10 WC Immunology SC Immunology GA PT424 UT WOS:A1994PT42400038 PM 7525307 ER PT J AU CARNES, M GOODMAN, BM LENT, SJ VO, H JAECKELS, R AF CARNES, M GOODMAN, BM LENT, SJ VO, H JAECKELS, R TI COINCIDENT PLASMA ACTH AND CORTICOSTERONE TIME-SERIES - COMPARISONS BETWEEN YOUNG AND OLD RATS SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE ACTH; GLUCOCORTICOIDS; AGING; TIME SERIES ANALYSIS; CHRONOBIOLOGY ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENOCORTICAL AXIS; DIMINISHED DIURNAL SECRETION; AGE-RELATED-CHANGES; CIRCADIAN-RHYTHM; SYSTEM; CORTISOL; HORMONE; RESPONSIVENESS; PLASTICITY AB Senescence is accompanied by a reduced ability to respond to a variety of physical acid behavioral stressors. A sizable literature has been devoted to the interplay between hypothalamic-pituitary-adrenocortical axis dysfunction and senescence; yet, the precise interactions remain an enigma. Adrenocorticotropic hormone (ACTH) is secreted in pulsatile bursts generating complex signals in the plasma compartment that must be ''read'' by adrenocortical cells in order to initiate appropriate secretory responses. We have previously demonstrated subtle differences between young and old rats in the pattern of fluctuations in plasma ACTH concentrations over time, despite no difference in mean levels. The present work addressed the physiological significance of these differences in the plasma ACTH Signal by analyzing the corresponding plasma corticosterone concentration time series and the relationship between these two hormones over time. Time series of integrated 10-min ACTH and corticosterone concentrations were collected over 4 h at the time of diurnal activation and analyzed in the time and frequency domains. The time of onset of the diurnal surge occurred 20 min later in old rats, and the ratio of corticosterone to ACTH was less at the time of onset and peak of the diurnal surge. Corticosterone levels were lower in old rats and mean ACTH and corticosterone levels were correlated in young but not old rats, as were maximum levels of the two hormones. Cross-correlation of ACTH and corticosterone time series and comparison of spectra were consistent with smoother fluctuations in plasma corticosterone in old animals with less variability at time scales less than 55 min. We conclude that age may be associated with a delay in diurnal activation of the HPA axis, a loss of sensitivity of adrenal corticosterone secretion to plasma ACTH levels, and a relative loss of high frequency variability in the corticosterone signal, as seen in many physiological systems with age. RP CARNES, M (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,GRECC,2500 OVERLOOK TERRACE,ROOM B-2091,MADISON,WI 53705, USA. FU NIDDK NIH HHS [DK-40759] NR 68 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD NOV-DEC PY 1994 VL 29 IS 6 BP 625 EP 643 DI 10.1016/0531-5565(94)90075-2 PG 19 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA PU887 UT WOS:A1994PU88700003 PM 9435915 ER PT J AU DEACON, TW PAKZABAN, P BURNS, LH DINSMORE, J ISACSON, O AF DEACON, TW PAKZABAN, P BURNS, LH DINSMORE, J ISACSON, O TI CYTOARCHITECTONIC DEVELOPMENT, AXON GLIA RELATIONSHIPS, AND LONG-DISTANCE AXON GROWTH OF PORCINE STRIATAL XENOGRAFTS IN RATS SO EXPERIMENTAL NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; ACID-LESIONED STRIATUM; ADULT-RATS; INTRASTRIATAL GRAFTS; EFFERENT PROJECTIONS; HUNTINGTONS-DISEASE; NEURITE GROWTH; HOST BRAIN; DOPAMINERGIC INNERVATION; NEOSTRIATAL TRANSPLANTS AB Porcine fetal lateral ganglionic eminence cells were transplanted into the quinolinic-acid-lesioned corpus striatum of immunosuppressed adult rats. The resulting grafts were analyzed for graft development with respect to donor age, donor cell dosage, and survival time from 5 to 22 weeks postimplantation. Graft development is prolonged by a factor of 3-4 times in porcine xenografts as compared to rat allografts. As grafts matured, neuronal somata developed in clusters that expressed acetylcholinesterase (AChE), tyrosine hydroxylase, and dopamine- and cAMP-associated phosphoprotein. These clusters were interspersed with AChE-poor graft regions consisting of small densely packed cells that stained for glial fibrillary acidic protein and porcine cluster of differentiation factor 44 (a species-specific glial marker). Graft axons could be selectively stained for 70-kDa neurofilament and were preferentially associated with AChE-poor, glial-rich regions in younger grafts (8 weeks), but AChE-rich neuronal regions in older grafts (22 weeks). Both graft axons and graft glial fibers projected for long distances into the host internal capsule, external capsule, corpus callosum, and anterior commissure. Donor axons also innervated host target structures including the globus pallidus and substantia nigra. This demonstrates a prolonged development of striatal cells that is appropriate to the donor species and which produces long-distance target-specific axonal growth within the adult host brain. (C) 1994 Academic Press, Inc. 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. DIACRIN INC, BOSTON, MA 02129 USA. BOSTON UNIV, BOSTON, MA 02215 USA. FU NINDS NIH HHS [5T32 NS07340, NS29178, NS30064] NR 97 TC 62 Z9 62 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 1994 VL 130 IS 1 BP 151 EP 167 DI 10.1006/exnr.1994.1194 PG 17 WC Neurosciences SC Neurosciences & Neurology GA QA957 UT WOS:A1994QA95700017 PM 7821391 ER PT J AU DIAMOND, MP BACHUS, K BIEBER, E BRADSHAW, K GALLUP, D GRUNERT, G MOK, A MORRIS, R PEREZ, R RADWANSKA, E SILVERBERG, K STEINKAMPF, M HALPERN, E FLEMING, L SMITH, E AF DIAMOND, MP BACHUS, K BIEBER, E BRADSHAW, K GALLUP, D GRUNERT, G MOK, A MORRIS, R PEREZ, R RADWANSKA, E SILVERBERG, K STEINKAMPF, M HALPERN, E FLEMING, L SMITH, E TI IMPROVEMENT OF INTEROBSERVER REPRODUCIBILITY OF ADHESION SCORING SYSTEMS SO FERTILITY AND STERILITY LA English DT Article DE ADHESIONS; SCORING METHOD; VIDEORECORDING AB Objective: To compare the interobserver reproducibility of two adhesion scoring methods, a more comprehensive adhesion scoring method and the American Fertility Society (AFS) adhesion scoring method. Design: Eleven endoscopic surgeons independently evaluated and scored 13 surgical video recordings using both systems. Material and Methods: The standardized AFS adhesion scoring method and the more comprehensive adhesion scoring method were utilized to assess abdominal adhesions. The more comprehensive adhesion scoring method scored 23 individual locations in the abdominal cavity for severity (0, none; 1, filmy, avascular; 2, vascular and/or dense; 3, cohesive) and extent of total area or length (0, none; 1, less than or equal to 25%; 2, 26% to 50%; 3, >50%). Because the best method of representing a composite adhesion score is unclear, the more comprehensive adhesion scoring method employed two independent methods of determining total score based on the severity and extent at each location, either adding severity plus extent or multiplying severity times extent before summing all 23 locations. Results: For each scoring method, a correlation coefficient was calculated for each of the 55 pairs of surgeons. Significant correlations were identified for all methods (AFS adhesion scoring method: 35 of 55, 64%; more comprehensive adhesion scoring method: severity plus extent, 49 of 55, 89%; and more comprehensive adhesion scoring method: severity times extent, 53 of 55, 96%). When the more comprehensive adhesion scoring method is limited to 13 areas in the lower pelvis corresponding to the locations represented in the AFS adhesion scoring method, the proportion of significant correlation coefficients become 54 of 55 and 50 of 55 for severity plus extent and severity times extent, respectively. Conclusion: Although the AFS adhesion scoring method generated significant agreement between pairs of surgeons, less than a third correlated at the 0.7 level. Use of the more comprehensive adhesion scoring method specifically demonstrating locations, severity, and extent of adhesions produced a marked increase in reproducibility between surgeon pairs in scoring pelvic adhesions. C1 DUKE UNIV,MED CTR,DURHAM,NC. UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. UNIV TEXAS,SOUTHWESTERN MED CTR,DALLAS,TX 75235. MED COLL GEORGIA,AUGUSTA,GA 30912. TEXAS WOMANS HOSP,HOUSTON,TX. MCGILL UNIV,MONTREAL GEN HOSP,MONTREAL H3G 1A4,PQ,CANADA. UNIV SO CALIF,LOS ANGELES,CA. MISSOURI BAPTIST HOSP,ST LOUIS,MO. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV TEXAS,MED CTR,SAN ANTONIO,TX 78285. UNIV ALABAMA,MED CTR,BIRMINGHAM,AL 35294. MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,CHARLESTON,MA. GENZYME CORP,CAMBRIDGE,MA. RP DIAMOND, MP (reprint author), VANDERBILT UNIV,MED CTR,DEPT OBSTET & GYNECOL,MCN C-1100,NASHVILLE,TN 37232, USA. OI Diamond, Michael/0000-0001-6353-4489 NR 2 TC 44 Z9 44 U1 1 U2 1 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD NOV PY 1994 VL 62 IS 5 BP 984 EP 988 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA PN136 UT WOS:A1994PN13600015 ER PT J AU ZIMMERMAN, M LISH, JD FARBER, NJ HARTUNG, J LUSH, D KUZMA, MA PLESCIA, G AF ZIMMERMAN, M LISH, JD FARBER, NJ HARTUNG, J LUSH, D KUZMA, MA PLESCIA, G TI SCREENING FOR DEPRESSION IN MEDICAL PATIENTS - IS THE FOCUS TOO NARROW SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; HEALTH-CARE UTILIZATION; PANIC DISORDER; SELF-REPORT; PSYCHIATRIC-DISORDERS; SOMATIZATION DISORDER; ADDICTIVE-DISORDERS; MENTAL-DISORDERS; SOCIAL MORBIDITY; CHEST PAIN AB There is growing consensus that depression is a major public health problem causing significant psychosocial morbidity and mortality which should be addressed by casefinding efforts in primary care settings. A large amount of literature has examined the ability of self-report questionnaires to detect depression in medical patients and the results have been encouraging. However, studies of general population and psychiatric patient samples indicate that depression is frequently comorbid with other psychiatric disorders, and that psychiatric disorders other than depression are also associated with significant morbidity and mortality. Consequently, we believe that psychiatric screening in primary care should be broad based. We administered a newly developed, multidimensional questionnaire (the SCREENER), that simultaneously screens for a range of DSM-III-R psychiatric disorders, to 508 medical outpatients attending a VA general medical clinic. Compared with nondepressed cases, the depressed patients significantly more often reported all of the nondepressive symptoms. Nine of the ten nondepressive disorders screened for by the SCREENER were significantly more frequent in the depressed group. Most patients who screened positive for depression also screened positive for at least one nondepressive disorder. Compared with patients who only screened positive for depression, those who screened positive for both depression and a nondepressive disorder rated their physical and emotional health more poorly and made more visits to the doctor. Compared with patients who did not screen positive for any disorder, those who only screened positive for a nondepressive disorder rated their physical and emotional health more poorly, and more frequently had a history of mental health treatment. C1 MED COLL PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19129. MED COLL PENN,DIV GEN MED,PHILADELPHIA,PA 19129. PHILADELPHIA VET AFFAIRS MED CTR,DEPT INTERNAL MED,PHILADELPHIA,PA. NR 59 TC 20 Z9 20 U1 4 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV PY 1994 VL 16 IS 6 BP 388 EP 396 DI 10.1016/0163-8343(94)90114-7 PG 9 WC Psychiatry SC Psychiatry GA PR841 UT WOS:A1994PR84100003 PM 7843575 ER PT J AU DONOVAN, JW MILNE, GT WEAVER, DT AF DONOVAN, JW MILNE, GT WEAVER, DT TI HOMOTYPIC AND HETEROTYPIC PROTEIN ASSOCIATIONS CONTROL RAD51 FUNCTION IN DOUBLE-STRAND BREAK REPAIR SO GENES & DEVELOPMENT LA English DT Article DE RAD51; RAD52; DOUBLE-STRAND BREAK REPAIR; SELF-ASSOCIATION; NEGATIVE DOMINANCE ID ESCHERICHIA-COLI RECA; SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE-SEQUENCE; DNA-REPLICATION; GENE-PRODUCTS; YEAST; RECOMBINATION; COMPLEX; HOMOLOG; CLONING AB Rad51 is essential for efficient repair of DNA double-strand breaks (DSBs) and recombination in Saccharomyces cerevisiae. Here, we examine Rad51 protein-protein interactions and their biological significance. GAL4 two-hybrid fusion analysis demonstrated that the amino-terminal region of Rad51 mediates both a strong Rad51:Rad51 self-association and a Rad51:Rad52 interaction. Several Rad51 variants were characterized that imparted DSB repair defects; these defects appear to result from Rad51 protein-protein interactions. First, a rad51 allele bearing a missense mutation in the consensus ATP-binding sequence disrupted DSB repair in wild-type yeast. The effect of this allele was dependent on the presence of wild-type Rad51 because MMS sensitivity of rad51 Delta strains were not increased by its expression. Second, we identified a highly conserved RAD51 homolog from Kluyveromyces lactis (KlRAD51) that only partially complemented rad51 Delta strains and impaired DSB repair in wild-type S. cerevisiae. Third, fusions of Gal4 domains to Rad51 disrupted DSB repair in a manner that required the presence of either Rad51 or Rad52. Because K. lactis RAD51 and RAD52 did not complement a S. cerevisiae rad51 Delta rad52 Delta strain, Rad51-Rad52 functions appear to be mediated through additional components. Thus, multiple types of Rad51 protein interactions, including self-association, appear to be important for DSB repair. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MICROBIOL & MOLEC GENET,DIV TUMOR IMMUNOL,BOSTON,MA 02115. NR 44 TC 101 Z9 101 U1 0 U2 1 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 NOV 1 PY 1994 VL 8 IS 21 BP 2552 EP 2562 DI 10.1101/gad.8.21.2552 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA PR220 UT WOS:A1994PR22000004 PM 7958917 ER PT J AU HANFSTINGL, U BERRY, A KELLOGG, EA COSTA, JT RUDIGER, W AUSUBEL, FM AF HANFSTINGL, U BERRY, A KELLOGG, EA COSTA, JT RUDIGER, W AUSUBEL, FM TI HAPLOTYPIC DIVERGENCE COUPLED WITH LACK OF DIVERSITY AT THE ARABIDOPSIS-THALIANA ALCOHOL-DEHYDROGENASE LOCUS - ROLES FOR BOTH BALANCING AND DIRECTIONAL SELECTION SO GENETICS LA English DT Article ID POLYMORPHISM LINKAGE MAP; DROSOPHILA-MELANOGASTER; ADH LOCUS; L HEYNH; NUCLEOTIDE POLYMORPHISM; MOLECULAR EVOLUTION; SEQUENCE-ANALYSIS; GENETIC-CONTROL; MAIZE; MUTATIONS AB We designate a region of the alcohol dehydrogenase locus (Adh) of the weedy crucifer, Arabidopsis thaliana, as ''hypervariable'' on the basis of a comparison of sequences from ecotypes Columbia and Landsberg. We found eight synonymous and two replacement mutations in the first 262 nucleotides of exon 4, and an additional two mutations in the contiguous region of intron 3. The rest of the sequence (2611 bp) has just three mutations, all of them confined to noncoding regions. Our survey of the hypervariable region among 37 ecotypes of A. thaliana revealed two predominant haplotypes, corresponding to the Columbia and Landsberg sequences. We identified five additional haplotypes and 4 additional segregating sites. The lack of haplotype diversity is presumably in part a function of low rates of recombination between haplotypes conferred by A. thaliana's tendency to self-fertilize. However, an analysis in 32 ecotypes of 12 genome-wide polymorphic markers distinguishing Columbia and Landsberg ecotypes indicated levels of outcrossing sufficient at least to erode linkage disequilibrium between dispersed markers. We discuss possible evolutionary explanations for the coupled observation of marked divergence within the hypervariable region and a lack of haplotype diversity among ecotypes. The sequence of the region for closely related species argues against the possibility that one allele is the product of introgression. We note (1) that several loss of function mutations (both naturally and chemically induced) map to the hypervariable region, and (2) the presence of two amino acid replacement polymorphisms, one of which causes the mobility difference between the two major classes of A. thaliana Adh electrophoretic alleles. We argue that protein polymorphism in such a functionally significant part of the molecule may be subject to balancing selection. The observed pattern of extensive divergence between the alleles is consistent with this explanation because balancing selection on a particular site maintains linked neutral polymorphisms at intermediate frequencies. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,MCZ LABS,CAMBRIDGE,MA 02138. UNIV MUNICH,INST BOT,D-80638 MUNICH,GERMANY. RP HANFSTINGL, U (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114, USA. RI Kellogg, Elizabeth/M-2845-2013 OI Kellogg, Elizabeth/0000-0003-1671-7447 NR 57 TC 86 Z9 91 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 1994 VL 138 IS 3 BP 811 EP 828 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA PP050 UT WOS:A1994PP05000025 PM 7851777 ER PT J AU HUTTNER, KM OUELLETTE, AJ AF HUTTNER, KM OUELLETTE, AJ TI A FAMILY OF DEFENSIN-LIKE GENES CODES FOR DIVERSE CYSTEINE-RICH PEPTIDES IN MOUSE PANETH CELLS SO GENOMICS LA English DT Article ID SMALL-INTESTINE; MESSENGER-RNA; CRYPTDIN LOCUS; HOST DEFENSE; PURIFICATION; AMPLIFICATION; NEUTROPHILS; EXPRESSION; SEQUENCE AB Cryptdins constitute a diverse population of defensins in Paneth cells of intestinal crypts. In mice, certain intestinal mRNAs, termed ''CRS1C'' and ''CRS4C,'' are considered to be cryptdin-related sequences, because their prepro-coding sequences are 94% identical to those of cryptdin-1 mRNA; however, their predicted products, which are cationic, cysteine-rich peptides, are not defensins (A. J. Ouellette and J. C. Lualdi, J. Biol. Chem. 265: 9831-9837, 1990). Here we describe several mouse small intestinal mRNAs and genes that code for CRS4C prepropeptides. The 10-kDa deduced CRS4C proteins consist of a prepro sequence, potential monobasic or dibasic peptide cleavage sites, a predicted 3.7-kDa peptide that contains 7 [C]-[X]-[Y] repeats, and a C(N/K)CNPK carboxyl-terminal consensus sequence. In situ hybridization experiments showed that CRS4C mRNAs are found in Paneth cells of adult small bowel. The CRS4C genes closely resemble cryptdin genes, having a two-exon structure with highly conserved transcription start sites, intron-exon junctions, and a single intron of approximate to 550 bp. Like the cryptdin genes, exon 1 of CRS4C genes consists of 5' untranslated sequences (UTS) and the prepro-coding region, and exon 2 codes for the predicted mature peptide and 3' UTS. Despite the similarity of first exons in CRS4C and cryptdin genes, their introns exhibit very little homology, and their second exons code for unrelated peptides. Analysis of introns suggests that the ancestral cryptdin and CRS4C genes may have diverged from a common ancestor in the distant past and expanded only recently. We speculate that the cryptdin/ CRS genes evolved so that prepro regions encoded by exon 1 were conserved to allow the varied peptides coded by exon 2 to be directed into Paneth cell secretory granules. (C) 1994 Academic Press,Inc. C1 HARVARD UNIV, SCH MED, HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT SURG, BOSTON, MA 02115 USA. CHILDRENS HOSP, JOINT PROGRAM NEONATOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, SURG SERV, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, SHRINERS BURNS INST, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK33506, DK44632] NR 38 TC 31 Z9 35 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 EI 1089-8646 J9 GENOMICS JI Genomics PD NOV 1 PY 1994 VL 24 IS 1 BP 99 EP 109 DI 10.1006/geno.1994.1586 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PT473 UT WOS:A1994PT47300013 PM 7896294 ER PT J AU HYMAN, SE GOLLUB, RL AF HYMAN, SE GOLLUB, RL TI MORE SEROTONIN - NOT AS SIMPLE AS IT SEEMS SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article RP HYMAN, SE (reprint author), MASSACHUSETTS GEN HOSP,MOLEC & DEV NEUROSCI LAB,CNY-2,149 13TH ST,BOSTON,MA 02129, USA. OI Gollub, Randy L./0000-0002-9434-4044 NR 2 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 1994 VL 2 IS 4 BP 222 EP 224 DI 10.3109/10673229409017140 PG 3 WC Psychiatry SC Psychiatry GA PU546 UT WOS:A1994PU54600005 PM 9384905 ER PT J AU GREGOR, P GASTON, SM YANG, XD OREGAN, JP ROSEN, DR TANZI, RE PATTERSON, D HAINES, JL HORVITZ, HR UHL, GR BROWN, RH AF GREGOR, P GASTON, SM YANG, XD OREGAN, JP ROSEN, DR TANZI, RE PATTERSON, D HAINES, JL HORVITZ, HR UHL, GR BROWN, RH TI GENETIC AND PHYSICAL MAPPING OF THE GLUR5 GLUTAMATE-RECEPTOR GENE ON HUMAN-CHROMOSOME-21 SO HUMAN GENETICS LA English DT Note ID AMYOTROPHIC-LATERAL-SCLEROSIS; EXPRESSION; SUBUNIT; LOCALIZATION; CHANNELS; LIBRARY; CLONES; CLONING; KAINATE; PROTEIN AB Glutamate receptors (GluRs) mediate excitatory neurotransmission and may have important roles in central nervous system disorders. To characterize the human GLUR5 gene, which is located on human chromosome 21q22.1, we isolated cDNAs, genomic phage lambda clones, and yeast artificial chromosomes (YACs) and developed sequence tagged sites (STSs) and simple sequence length polymorphisms (SSLPs) for GLUR5. Genetic mapping with a tetranucleotide AGAT repeat named GLUR5/AGAT (six alleles observed, 70% heterozygosity) placed GLUR5 5 cM telomeric to APP (D21S210) and 3cM centromeric to SOD1 (D21S223). The human GLUR5 gene is located near the familial amyotrophic lateral sclerosis (FALS) locus; linkage analysis of GLUR5 SSLPs in FALS pedigrees yielded negative lod scores, consistent with the recent association of the FALS locus with the SOD1 gene. Physical mapping of GLUR5 using a YAC contig suggested that the GLUR5 gene spans approximately 400-500kb, and is within 280kb of D21S213. The large size of the GLUR5 gene raises questions regarding its functional significance. Our GLUR5 YAC contig includes clones found in the Genethon chromosome 21 YAC contig, and reference to the larger contig indicates the orientation centromere - D21S213 - GLUR5 5' end-GLUR5/AGAT - GLUR5 3'- end - SOD1. The development of GLUR5/AGAT should permit rapid determination of the status of the GLUR5 gene in individuals with partial trisomy or monosomy of chromosome 21. Such studies may provide insights concerning the possible role of GLUR5 in Down syndrome. C1 MASSACHUSETTS GEN HOSP,GENET & AGING LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DAY NEUROMUSC RES CTR,BOSTON,MA 02129. ELEANOR ROOSEVELT INST CANC RES,DENVER,CO 80206. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. MIT,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. RP GREGOR, P (reprint author), NIDA,ADDICT RES CTR,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224, USA. RI Haines, Jonathan/C-3374-2012 FU NHGRI NIH HHS [HG00324]; NIA NIH HHS [AG00029]; NICHD NIH HHS [HD17449] NR 23 TC 13 Z9 13 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 1994 VL 94 IS 5 BP 565 EP 570 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA PP896 UT WOS:A1994PP89600022 PM 7959697 ER PT J AU MARY, JL BISHOP, T KOLODNER, R LIPFORD, JR KANE, M WEBER, W TORHORST, J MULLER, H SPYCHER, M SCOTT, RJ AF MARY, JL BISHOP, T KOLODNER, R LIPFORD, JR KANE, M WEBER, W TORHORST, J MULLER, H SPYCHER, M SCOTT, RJ TI MUTATIONAL ANALYSIS OF THE HMSH2 GENE REVEALS A 3-BASE-PAIR DELETION IN A FAMILY PREDISPOSED TO COLORECTAL-CANCER DEVELOPMENT SO HUMAN MOLECULAR GENETICS LA English DT Note ID NONPOLYPOSIS C1 KANTONSSPITAL, RES DEPT, BASEL, SWITZERLAND. ICRF, LEEDS, W YORKSHIRE, ENGLAND. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. KANTONSSPITAL, INST PATHOL, BASEL, SWITZERLAND. KANTONSSPITAL, DEPT MED GENET, BASEL, SWITZERLAND. FU NIGMS NIH HHS [GM50006] NR 12 TC 46 Z9 47 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 NOV PY 1994 VL 3 IS 11 BP 2067 EP 2069 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PT231 UT WOS:A1994PT23100026 PM 7874129 ER PT J AU AZIZASHUSTER, E AF AZIZASHUSTER, E TI A CHILD AT ALL COSTS - POSTHUMOUS REPRODUCTION AND THE MEANING OF PARENTHOOD SO HUMAN REPRODUCTION LA English DT Article DE ASSISTED REPRODUCTION; CRYOPRESERVATION OF SPERM AND EMBRYOS; GAMETE DONATION; POSTHUMOUS REPRODUCTION AB The creation of babies by assisted and collaborative techniques of reproduction, such as in-vitro fertilization or cryopreservation of gametes and embryos, stimulates strong emotions and fantasies about life, death, sexuality and immortality. Particularly, the cryopreservation of spermatozoa for post-mortem reproduction forces us to come to terms with the meaning of human reproduction, and the extent of individual rights to procreate using artificial means. RP AZIZASHUSTER, E (reprint author), DEPT VET AFFAIRS MED CTR,ETH PROGRAM,PHILADELPHIA,PA 19104, USA. NR 11 TC 16 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 1994 VL 9 IS 11 BP 2182 EP 2185 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA PU209 UT WOS:A1994PU20900043 PM 7868695 ER PT J AU GRANJA, CB GOZASHTI, CS DASGUPTA, JD AF GRANJA, CB GOZASHTI, CS DASGUPTA, JD TI CD4-INDEPENDENT SIGNAL-TRANSDUCTION THROUGH THE T-CELL RECEPTOR (TCR/CD3) SO IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; ANTIGEN RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; MONOCLONAL-ANTIBODY; CROSS-LINKING; C ACTIVATION; ZETA-CHAIN; CD4; PHOSPHORYLATION; ASSOCIATION AB The membrane-bound CD4 glycoprotein has been proposed to act like a co-receptor along with the T-cell antigen receptor (TCR/CD3) during ligand recognition and cell activation. Due to its association with the protein tyrosine kinase (PTK) p56(lck), CD4 is believed to transduce a signal and support CD3 activation of T cells. In this study we have shown that CD3 ligation on murine T-cell hybridomas induces tyrosine phosphorylation of proteins, including phospholipase C-yl (PLC gamma 1), both in the presence as well as in the absence of CD4-linked p56(lck). Furthermore, using HPB clones deficient in CD3/PTK association, it has been found that the presence of CD4/p56(lck) does not overcome the defect in signalling. Not even co-aggregation of CD4 with CD3 triggers tyrosine phosphorylation of proteins in these cells. Together, the present results indicate that CD3-linked PTK(s) plays a primary role in the induction of signalling through TCR/CD3, and the presence of CD4/p56(lck) is neither necessary nor sufficient to elicit these events. In the light of these results a possible role for CD4 in antigen presentation has been proposed. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,BOSTON,MA. NR 42 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD NOV PY 1994 VL 83 IS 3 BP 414 EP 419 PG 6 WC Immunology SC Immunology GA PP779 UT WOS:A1994PP77900014 PM 7835966 ER PT J AU CHIAPPELLI, F FROST, P MANFRINI, E LEE, P PHAM, L GARCIA, C DALEY, S KUNG, M VILLANUEVA, P AF CHIAPPELLI, F FROST, P MANFRINI, E LEE, P PHAM, L GARCIA, C DALEY, S KUNG, M VILLANUEVA, P TI COCAINE BLUNTS HUMAN CD4(+) CELL ACTIVATION SO IMMUNOPHARMACOLOGY LA English DT Article DE COCAINE; HUMAN T LYMPHOCYTE; CD4(+) CELL ACTIVATION ID BLOOD T-LYMPHOCYTES; BETA-ENDORPHIN; PROLIFERATION; INVITRO; EXPRESSION; MOLECULE; SURFACE; MICE AB Cocaine is reported to be immunotoxic. The biochemical mechanisms responsible for the immunopharmacological outcomes of cocaine in vivo and in vitro remain, however, to be fully elucidated. Our experimental data confirm that exposure of normal human T cells to micromolar concentrations of cocaine modulates T-cell responses to stimulation by a variety of stimuli, and indicate that cocaine impairs early activation events during CD4(+) but not CD4(-) T-cell stimulation. Pre-incubation of enriched CD4(+) T-cell subpopulations that express the homing receptor CD62L with nanomolar concentrations of the endogenous opioid peptide beta-endorphin leads to a more severe impairment of activation than that noted following pre-incubation with micromolar concentrations of cocaine alone. These findings begin to elucidate the molecular and cellular mechanisms of the immunopathology of cocaine. Our data support the proposition that cocaine abuse may place cocaine-abuser HIV-seropositive individuals at increased risk of opportunistic infections. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT ANAT & CELL BIOL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,HUMAN IMMUNOL & PSYCHONEUROIMMUNOL LAB,LOS ANGELES,CA 90073. UNIV ANCONA,ANCONA,ITALY. UNIV CALIF LOS ANGELES,DEPT BIOL,LOS ANGELES,CA 90024. RP CHIAPPELLI, F (reprint author), UNIV CALIF LOS ANGELES,SCH DENT,HUMAN ORAL & MOLEC IMMUNOL LAB,LOS ANGELES,CA 90024, USA. OI Frost, Patrick/0000-0003-3348-5983 FU NIDA NIH HHS [NIDA-07683]; PHS HHS [GR 6773-01] NR 35 TC 12 Z9 12 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD NOV-DEC PY 1994 VL 28 IS 3 BP 233 EP 240 DI 10.1016/0162-3109(94)90059-0 PG 8 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA PN500 UT WOS:A1994PN50000008 PM 7852054 ER PT J AU OUELLETTE, AJ HSIEH, MM NOSEK, MT CANOGAUCI, DF HUTTNER, KM BUICK, RN SELSTED, ME AF OUELLETTE, AJ HSIEH, MM NOSEK, MT CANOGAUCI, DF HUTTNER, KM BUICK, RN SELSTED, ME TI MOUSE PANETH CELL DEFENSINS - PRIMARY STRUCTURES AND ANTIBACTERIAL ACTIVITIES OF NUMEROUS CRYPTDIN ISOFORMS SO INFECTION AND IMMUNITY LA English DT Article ID SMALL-INTESTINE; ANTIMICROBIAL PEPTIDES; NEUTROPHIL DEFENSIN; MESSENGER-RNA; GENE-EXPRESSION; HOST DEFENSE; CDNA CLONES; EPITHELIUM; DIFFERENTIATION; PURIFICATION AB Cryptdins are antimicrobial peptides of the defensin family that are produced by intestinal Paneth cells. mRNAs encoding 17 cryptdin isoforms have been characterized from a cDNA library generated from a single jejunal crypt. Six cryptdin cDNAs correspond to known peptides, and the remainder predict 11 novel Paneth cell defensins. Most cryptdin cDNAs have greater than or equal to 93% nucleotide sequence identity overall, except for cryptdin 4 and 5 cDNAs, whose respective mature peptide encoding regions are only 74 and 78% identical to that of cryptdin 1. Cryptdin cDNAs differ at a small number of nucleotide positions: frequent substitutions were found in codons 38 and 52 of the propiece and in codons 68, 73, 76, 87, and 89 of the deduced peptides; cDNA clones with changes in codons 74, 83, and 88 were found, but there were fewer of these. The antimicrobial activities of cryptdins 1 to 6 were tested against Escherichia call ML35 in two assays. In an agar diffusion assay, the potencies of cryptdins 1 to 3, 5, and 6 were approximately equivalent to that of rabbit neutrophil defensin NP-1 but cryptdin 4 was 30 times more active than NP-1. In a bactericidal assay system, cryptdins 1 and 3 to 6 were equally active at 10 mu g/ml but cryptdin 2 and rabbit NP-1 were not active at this concentration. Since cryptdins 2 and 3 differ only ah residue 10 (Thr and Lys, respectively), this amino acid appears to function in bactericidal interaction with E. coli. The demonstration that Paneth cells express a diverse population of microbicidal defensins further implicates cryptdins in restricting colonization or invasion of small intestinal epithelium by bacteria. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT BIOL CHEM,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT GENET,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. UNIV CALIF IRVINE,COLL MED,DEPT PATHOL,IRVINE,CA 92717. UNIV CALIF IRVINE,COLL MED,DEPT MICROBIOL & MOLEC GENET,IRVINE,CA 92717. UNIV TORONTO,ONTARIO CANC INST,TORONTO M4X 1K9,ON,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO M4X 1K9,ON,CANADA. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,JOINT PROGRAM NEONATOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI22931]; NIDDK NIH HHS [DK33506, DK44632] NR 63 TC 161 Z9 181 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1994 VL 62 IS 11 BP 5040 EP 5047 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PN304 UT WOS:A1994PN30400049 PM 7927786 ER PT J AU BELDEN, WJ MILLER, SI AF BELDEN, WJ MILLER, SI TI FURTHER CHARACTERIZATION OF THE PHOP REGULON - IDENTIFICATION OF NEW PHOP-ACTIVATED VIRULENCE LOCI SO INFECTION AND IMMUNITY LA English DT Article ID SALMONELLA-TYPHIMURIUM VIRULENCE; OUTER-MEMBRANE PROTEIN; YERSINIA-ENTEROCOLITICA; GENETIC-ANALYSIS; VIBRIO-CHOLERAE; RESISTANCE; MACROPHAGE; INVASION; CELLS; DETERMINANTS AB Salmonella typhimurium survival within macrophages is an essential virulence property necessary to enteric fever pathogenesis. This survival requires coordinate transcriptional activation of virulence genes within acidified macrophage phagosomes. Virulence gene transcription is regulated by a two-component system comprising the PhoP (transcriptional activator) and PhoQ (sensor-kinase) proteins. Thirteen new PhoP-activated loci (designated pagD to pagP) encoding membrane or secreted proteins have been identified by use of the transposon TnphoA. Three of these loci have a chromosomal location that was linked to the previously identified pagC locus. Strains with TnphoA insertions in pagD, pagJ, pagK, and pagM were significantly attenuated for mouse-virulence (50% lethal dose greater than 1,000 times that of wild-type bacteria). No strains with pag::TnphoA insertions were found to have altered sensitivity to the cationic antimicrobial peptide NP-1 defensin. PhoP and PhoQ are pleotropic regulators of membrane or secreted proteins, suggesting that the ability to effect a global change in the expression of these proteins is required for S. typhimurium survival within acidified macrophage phagosomes. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIAID NIH HHS [AI30479] NR 37 TC 99 Z9 101 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1994 VL 62 IS 11 BP 5095 EP 5101 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PN304 UT WOS:A1994PN30400055 PM 7927792 ER PT J AU IGIETSEME, JU MAGEE, DM WILLIAMS, DM RANK, RG AF IGIETSEME, JU MAGEE, DM WILLIAMS, DM RANK, RG TI ROLE FOR CD8(+) T-CELLS IN ANTICHLAMYDIAL IMMUNITY DEFINED BY CHLAMYDIA-SPECIFIC T-LYMPHOCYTE CLONES SO INFECTION AND IMMUNITY LA English DT Note ID FEMALE GUINEA-PIGS; TUMOR NECROSIS FACTOR; GENITAL-INFECTION; INCLUSION CONJUNCTIVITIS; GAMMA INTERFERON; HOST DEFENSE; ROLE INVIVO; TRACHOMATIS; MICE; RESOLUTION AB The role of CD8(+). T cells in antichlamydial immunity was investigated in a murine model of chlamydial genital infection by using T-cell clones generated against the Chlamydia trachomatis agent of mouse pneumonitis (MoPn). Two CD8(+) T-cell clones tested (2.1F and 2.14-9) were chlamydia antigen specific and MHC restricted and reacted against MoPn as well as the Chlamydia psittaci agent of guinea pig inclusion conjunctivitis and C. trachomatis serovar E, suggesting the recognition of a genus-specific antigen. Upon adoptive transfer into persistently MoPn-infected nu/nu mice, 55.6% of the recipients of clone 2.1F (15 of 27) resolved the infection but recipients of clone 2.14-9 did not. The ability to resolve the MoPn infection correlated with the capacity of clone 2.1F to elaborate a combination of gamma interferon and tumor necrosis factor alpha. The results suggested that in addition to CD4(+) T cells, CD8(+) T cells may also contribute to anti-chlamydial T-cell immunity in vivo. C1 AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RP IGIETSEME, JU (reprint author), UNIV ARKANSAS MED SCI HOSP,DEPT IMMUNOL & MICROBIOL,4301 MARKHAM ST,SLOT 511,LITTLE ROCK,AR 72205, USA. FU NIAID NIH HHS [AI26328] NR 29 TC 89 Z9 91 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1994 VL 62 IS 11 BP 5195 EP 5197 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PN304 UT WOS:A1994PN30400073 PM 7927806 ER PT J AU KNISELY, TL GRABBE, S NAZARENO, R GRANSTEIN, RD AF KNISELY, TL GRABBE, S NAZARENO, R GRANSTEIN, RD TI PRODUCTION OF INTERLEUKIN-6 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR BY MURINE IRIS AND CILIARY BODY EXPLANTS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE IRIS; CILIARY BODY; CYTOKINES; SYNTHESIS; IMMUNOREGULATION ID GROWTH-FACTOR-BETA; EPIDERMAL LANGERHANS CELLS; HUMAN-ENDOTHELIAL CELLS; NECROSIS FACTOR-ALPHA; AQUEOUS-HUMOR; THYMOCYTE PROLIFERATION; MONONUCLEAR PHAGOCYTES; DENDRITIC CELLS; HUMAN-MONOCYTES; IL-6 AB Purpose. To examine the ability of murine iris-ciliary body explants to produce cytokines with proinflammatory activities. Methods. Supernatants derived from murine iris-ciliary body (I-CB) tissue explants cultured (four per well in 1 ml medium) in the presence of indomethacin were analyzed for the production of IL-1, IL-2, IL-3, IL-6, tumor necrosis factor-alpha/beta (TNF alpha/beta) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Analysis was performed by thymocyte costimulation, growth factor-dependent cell proliferation, TGF-beta-sensitive mink lung epithelial cell proliferation, and enzyme-linked immunosorbent assays (ELISA). Results. Supernatants from I-CB explants cultured in vitro for 24 hours contained significant thymocyte costimulatory activity. This activity was fully neutralized by a combination of antisera to IL-1 and IL-6, and ELISA analysis confirmed that IL-6 was a significant component of the supernatant (402.1 pg/ml). TNF alpha/beta were also found in low concentrations (similar to 2.0 U/ml) by ELISA analysis, whereas IL-2 and IL-4 were not detectable. Significant amounts of GM-CSF (15.8 U/ml), but no IL-3, were detected. Conclusions. These results demonstrate that normal I-CB tissue contains cells capable of producing IL-6, GM-CSF, and IL-1. Because of the proinflammatory nature of IL-6 and IL 1, and the ability of GM-CSF, IL-1, and IL-6 to enhance functional capabilities of antigen presenting cells, regulation of the production of these cytokines may contribute significantly to the maintenance of the immunologic status of this regional site. C1 MASSACHUSETTS GEN HOSP,HARVARD CUTAEOUS BIOL RES CTR,DEPT DERMATOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. FU NEI NIH HHS [EY07782] NR 50 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 1994 VL 35 IS 12 BP 4015 EP 4022 PG 8 WC Ophthalmology SC Ophthalmology GA PQ608 UT WOS:A1994PQ60800007 PM 7960583 ER PT J AU ROOF, DJ ADAMIAN, M HAYES, A AF ROOF, DJ ADAMIAN, M HAYES, A TI RHODOPSIN ACCUMULATION AT ABNORMAL SITES IN RETINAS OF MICE WITH A HUMAN P23H RHODOPSIN TRANSGENE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RHODOPSIN; RETINAL DEGENERATION; TRANSGENIC MICE; RETINITIS PIGMENTOSA; PHOTORECEPTOR SYNAPSE ID DOMINANT RETINITIS-PIGMENTOSA; PHOSPHODIESTERASE BETA-SUBUNIT; PERIPHERIN-RDS GENE; CGMP-PHOSPHODIESTERASE; PHOTORECEPTOR CELLS; MONOCLONAL-ANTIBODIES; POINT MUTATION; ONE FORM; DEGENERATION; MOUSE AB Purpose. To investigate the mechanism by which photoreceptors degenerate in transgenic mice carrying a mutant human rhodopsin gene (P23H). Methods. The temporal and spatial pattern of the retinal degeneration caused by P23H rhodopsin was mapped using immunocytochemistry with rhodopsin-specific antibodies. The subcellular localizations of rhodopsin, transducin, and rod cGMP phosphodiesterase (PDE) were also determined, and rhodopsin localization was compared among P23H transgenic mice, rd mice, and Royal College of Surgeons (RCS) rats. Results. In transgenic mice that express P23H rhodopsin, photoreceptors are lost centrally by postnatal day 10. As the retina degenerates, rhodopsin accumulates in the outer nuclear layer and within the photoreceptor synaptic terminals. The P23H transgenic retinas also show an accumulation of transducin and PDE within the outer plexiform layer. In contrast, other types of hereditary retinal degenerations studied show a similar pattern of rhodopsin accumulation in the outer nuclear layer but not in the outer plexiform layer of the retina. Conclusions. The pattern of degeneration in the P23H transgenic retina is consistent with a model in which the centrally located, first-born photoreceptors are the first to die. In contrast to other animal models for hereditary retinal degeneration (rd, RCS), a novel feature of the P23H degeneration is an accumulation of rhodopsin, transducin, and PDE within the outer plexiform layer of the retina. One hypothesis to explain this observation is that P23H rhodopsin is routed intracellularly through a pathway not used by normal rhodopsin. Nonmutant forms of the peripheral transducing proteins normally associated with disk membrane, such as transducin and PDE, may accompany the aberrantly routed rhodopsin. RP ROOF, DJ (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY10098, EY06514] NR 40 TC 96 Z9 97 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 1994 VL 35 IS 12 BP 4049 EP 4062 PG 14 WC Ophthalmology SC Ophthalmology GA PQ608 UT WOS:A1994PQ60800011 PM 7960587 ER PT J AU OTTO, MW MCNALLY, RJ POLLACK, MH CHEN, E ROSENBAUM, JF AF OTTO, MW MCNALLY, RJ POLLACK, MH CHEN, E ROSENBAUM, JF TI HEMISPHERIC LATERALITY AND MEMORY BIAS FOR THREAT IN ANXIETY DISORDERS SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Note ID PERCEPTUAL ASYMMETRY; PANIC DISORDER; CEREBRAL LATERALITY; DEPRESSION; EMOTION AB The authors examined auditory perceptual asymmetries and explicit memory biases for threat in patients with panic disorder and generalized anxiety disorder relative to healthy control subjects. They did not find a greater explicit memory bias for threat in the anxiety patients. However, explicit memory biases for threat were associated with perceptual asymmetry scores; patients with a greater right-ear (left hemisphere) advantage exhibited an explicit memory bias for threat material, whereas patients with a lower right-ear advantage displayed apparent cognitive avoidance of threat material. Memory for threat words was unrelated to perceptual asymmetry in healthy control subjects. These findings suggest that neuropsychological variables may partly determine the degree to which anxiety patients process threatening stimuli. C1 HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP OTTO, MW (reprint author), MASSACHUSETTS GEN HOSP,BEHAV THERAPY UNIT,WACC-815,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH 19600, MH 43809] NR 22 TC 21 Z9 22 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 1994 VL 103 IS 4 BP 828 EP 831 DI 10.1037//0021-843X.103.4.828 PG 4 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA PQ963 UT WOS:A1994PQ96300028 PM 7822587 ER PT J AU BURTON, MD NOURI, K BAICHOO, S SAMUELSTOYLOY, N KAZEMI, H AF BURTON, MD NOURI, K BAICHOO, S SAMUELSTOYLOY, N KAZEMI, H TI VENTILATORY OUTPUT AND ACETYLCHOLINE - PERTURBATIONS IN RELEASE AND MUSCARINIC RECEPTOR ACTIVATION SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE CONTROL OF BREATHING; ISOLATED BRAIN STEM; CETIEDIL; VESAMICOL; 4-AMINOPYRIDINE; MUSCARINIC BLOCKERS; TETRAETHYLAMMONIUM CHLORIDE ID STEM-SPINAL-CORD; CENTRAL HYPOVENTILATION SYNDROME; RESPIRATORY RHYTHM GENERATION; TORPEDO ELECTRIC ORGAN; BRAIN-STEM; HEART-RATE; NEWBORN RAT; SYNAPTIC VESICLES; NEONATAL RAT; 4-AMINOPYRIDINE AB Cholinergic transmission may be part of the normal neurochemical processes that support spontaneous ventilation. If this is true, perturbations in acetylcholine (ACh) turnover should alter ventilatory output in a predictable manner. With the use of the isolated perfused brain stem-spinal axis from the neonatal rat, the effects of modifiers of ACh release and blockers of muscarinic receptors on spontaneous C-4 (phrenic) output were determined. Vesamicol and cetiedil, inhibitors of ACh release, caused depression and cessation of the C-4 output in a dose-dependent manner when added to the perfusate. Muscarinic blockers, particularly M(1) and M(3) blockers, caused a similar depression. 4-Aminopyridine and tetraethylammonium chloride, facilitators of ACh release, caused stimulation of C-4 (phrenic) output. The depressive effects of the blockers and inhibitors were reversible with facilitation of ACh release except in the case of cetiedil. These findings are consistent with the view that the synaptic turnover of endogenous ACh is an important part of the normal neurochemical process that supports and modulates ventilation. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP BURTON, MD (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, PULM & CRIT CARE UNIT, BOSTON, MA 02114 USA. FU NCRR NIH HHS [2SO3-RR-O3546-02, 2SO3-RR-O3546-O1] NR 45 TC 38 Z9 38 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 EI 1522-1601 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1994 VL 77 IS 5 BP 2275 EP 2284 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PQ375 UT WOS:A1994PQ37500032 PM 7868445 ER PT J AU RING, D VACCARO, AR SCUDERI, G PATHRIA, MN GARFIN, SR AF RING, D VACCARO, AR SCUDERI, G PATHRIA, MN GARFIN, SR TI ACUTE CALCIFIC RETROPHARYNGEAL TENDINITIS - CLINICAL PRESENTATION AND PATHOLOGICAL CHARACTERIZATION SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID LONGUS COLLI; NECK PAIN; CT AB Acute calcific retropharyngeal tendinitis is an underrecognized cause of pain and stiffness in the neck associated with odynophagia and retropharyngeal soft-tissue swelling. We report on five patients in whom an initial misdiagnosis of this entity as a retropharyngeal or nasopharyngeal abscess, a neoplasm, or a fracture-dislocation of the cervical spine led to interventions such as admission to the hospital and parenteral administration of antibiotics. An open biopsy was performed in one patient because of a suspected neoplasm. Evaluation of the tissue specimen with routine and polarized light microscopy, scanning electron microscopy, and energy-dispersive spectrometry demonstrated a foreign-body inflammatory response to deposited crystals of hydroxyapatite. In all five patients, the correct diagnosis was established only after retrospective review of the radiographic studies by a physician who was familiar with acute calcific retropharyngeal tendinitis. The computed tomographic findings of acute calcific retropharyngeal tendinitis are distinctive and consist of prevertebral calcification localized to the insertion of an edematous tendon of the longus colli muscle. Symptomatic relief was provided with anti-inflammatory and analgesic medications. The symptoms resolved, without sequelae, within one to two weeks for all of the patients. We hope that an increased awareness of hydroxyapatite deposition in the tendon of the longus colli muscle will result in improved early diagnosis of acute calcific retropharyngeal tendinitis. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT ORTHOPAED SURG,PHILADELPHIA,PA 19107. UNIV CALIF SAN DIEGO,SCH MED,SAN DIEGO,CA 92103. RP RING, D (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,FRUIT ST,BOSTON,MA 02114, USA. NR 22 TC 68 Z9 69 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 1994 VL 76A IS 11 BP 1636 EP 1642 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PT189 UT WOS:A1994PT18900006 PM 7962023 ER PT J AU PESAVENTO, PA STEWART, RJ GOLDSTEIN, LSB AF PESAVENTO, PA STEWART, RJ GOLDSTEIN, LSB TI CHARACTERIZATION OF THE KLP68D KINESIN-LIKE PROTEIN IN DROSOPHILA - POSSIBLE ROLES IN AXONAL-TRANSPORT SO JOURNAL OF CELL BIOLOGY LA English DT Article ID BINDING PROTEINS; SENSORY NEURONS; HEAVY-CHAIN; NCD PROTEIN; EMBRYOS; PATHWAYS; COMMON; MOTOR AB This paper describes the molecular and biochemical properties of KLP68D, a new kinesin-like motor protein in Drosophila melanogaster. Sequence analysis of a full-length cDNA encoding KLP68D demonstrates that this protein has a domain that shares significant sequence identity with the entire 340-amin acid kinesin heavy chain motor domain. Sequences extending beyond the motor domain predict a region of alpha-helical coiled-coil followed by a globular ''tail'' region; there is significant sequence similarity between the alpha-helical coiled-coil region of the KLP68D protein and similar regions of the KIF3 protein of mouse and the KRP85 protein of sea urchin. This finding suggests that ail three proteins may be members of the same family, and that they all perform related functions. KLP68D protein produced in Escherichia coli is, like kinesin itself, a plus-end directed microtubule motor. In situ hybridization analysis of KLP68D RNA in Drosophila embryos indicates that the KLP68D gene is expressed primarily in the central nervous system and in a subset of the peripheral nervous system during embryogenesis. Thus, KLP68D may be used for anterograde axonal transport and could conceivably move cargoes in fly neurons different than those moved by kinesin heavy chain or other plus-end directed motors. C1 UNIV CALIF SAN DIEGO,SCH MED,DEPT PHARMACOL,DIV CELLULAR & MOLEC MED,HOWARD HUGHES MED INST,LA JOLLA,CA 92093. DANA FARBER CANC INST,DEPT INFECT DIS,BOSTON,MA 02115. ROWLAND INST SCI INC,CAMBRIDGE,MA 02142. FU NIGMS NIH HHS [GM35252] NR 29 TC 61 Z9 62 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV PY 1994 VL 127 IS 4 BP 1041 EP 1048 DI 10.1083/jcb.127.4.1041 PG 8 WC Cell Biology SC Cell Biology GA PT483 UT WOS:A1994PT48300012 PM 7525600 ER PT J AU YOSHIDA, T LIMMROTH, V IRIKURA, K MOSKOWITZ, MA AF YOSHIDA, T LIMMROTH, V IRIKURA, K MOSKOWITZ, MA TI THE NOS INHIBITOR, 7-NITROINDAZOLE, DECREASES FOCAL INFARCT VOLUME BUT NOT THE RESPONSE TO TOPICAL ACETYLCHOLINE IN PIAL VESSELS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ACETYLCHOLINE; FOCAL CEREBRAL ISCHEMIA; NEURONAL NITRIC OXIDE SYNTHASE; NITRIC OXIDE; 7-NITROINDAZOLE ID NITRIC-OXIDE SYNTHASE; CEREBRAL-ARTERY OCCLUSION; L-ARGININE; 7-NITRO INDAZOLE; BLOOD-FLOW; ISCHEMIA; RAT; BRAIN; MECHANISMS; PATHWAY AB We examined whether 7-nitroindazole (7-NI), a putative inhibitor of neuronal nitric oxide synthase (nNOS), decreases cerebral infarction 24 h after proximal middle cerebral artery (MCA) occlusion. In preliminary experiments, we determined that 7-NI (25, 50, and 100 mg/kg i.p.) decreased nitric oxide synthase (NOS) activity within cerebral cortex by 40-60% when measured up to 120 min, but not 240 min after administration. At 25 or 50 mg/kg, 7-NI did not alter the systemic arterial blood pressure or the dilation of pial arterioles after topical acetylcholine (10 and 100 mu M). To examine the effect of 7-NI on infarct size, 55 Sprague-Dawley halothaneanesthetized rats were subjected to proximal MCA occlusion (modified Tamura method). Five minutes after occlusion, 7-NI (25 or 50 mg/kg i.p.) or vehicle was injected. Animals treated with 25 or 50 mg/kg showed 25 and 27% reductions in infarct volume, respectively. Coadministration of L-arginine (300 mg/kg i.p.) plus 7-NI (25 mg/kg i.p.) reversed the effect. If, indeed, the effects of 7-NI are mediated by inhibition of nNOS activity, these results suggest that enzymatic products of the neuronal isoform promote ischemic injury and that they do so at least within the first few hours after permanent occlusion. The results also emphasize the importance of developing strategies to selectively inhibit the neuronal isoform inasmuch as we observed previously that administering the less selective NOS inhibitor, N-omega-nitro-L-arginine (L-NA), in the same model either caused no change or increased the volume of ischemic injury. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, STROKE RES LAB, BOSTON, MA 02114 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS 21558, NS 64361] NR 36 TC 268 Z9 277 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1994 VL 14 IS 6 BP 924 EP 929 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA PM721 UT WOS:A1994PM72100005 PM 7523430 ER PT J AU ZHANG, ZG CHOPP, M MAYNARD, KI MOSKOWITZ, MA AF ZHANG, ZG CHOPP, M MAYNARD, KI MOSKOWITZ, MA TI CEREBRAL BLOOD-FLOW CHANGES DURING CORTICAL SPREADING DEPRESSION ARE NOT ALTERED BY INHIBITION OF NITRIC-OXIDE SYNTHESIS SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CBF CHANGES; CORTICAL SPREADING DEPRESSION; NITRIC OXIDE SYNTHESIS AB CBF increases concomitantly with cortical spreading depression (CSD). We tested the hypothesis that CBF changes during CSD are mediated by nitric oxide (NO). Male Wistar rats (n = 23) were subjected to KCl-induced CSD before and after administration of nitric oxide synthase (NOS) inhibitors N-nitro-L-arginine (L-NNA) or N-nitro-L-arginine methyl ester (L-NAME) and in nontreated animals. CBF, CSD, and mean arterial blood pressure were recorded. Brain NOS activity was measured in vitro in control, L-NNA, and L-NAME-treated rats by the conversion of [H-3]arginine to [3H]citrulline. Our data show that the NOS inhibitors did not significantly change regional CBF (rCBF) during CSD, even though cortical NOS activity was profoundly depressed and systemic arterial blood pressure was significantly increased. Our data suggest that rCBF during CSD in rats is not regulated by NO. C1 HENRY FORD HLTH SCI SYST,DEPT NEUROL,DETROIT,MI. OAKLAND UNIV,DEPT PHYS,ROCHESTER,MI. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE RES LAB,BOSTON,MA. RI Moskowitz, Michael/D-9916-2011 NR 13 TC 32 Z9 32 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1994 VL 14 IS 6 BP 939 EP 943 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA PM721 UT WOS:A1994PM72100007 PM 7523432 ER PT J AU SCHULZ, JB HENSHAW, DR JENKINS, BG FERRANTE, RJ KOWALL, NW ROSEN, BR BEAL, MF AF SCHULZ, JB HENSHAW, DR JENKINS, BG FERRANTE, RJ KOWALL, NW ROSEN, BR BEAL, MF TI 3-ACETYLPYRIDINE PRODUCES AGE-DEPENDENT EXCITOTOXIC LESIONS IN RAT STRIATUM SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE 3-ACETYLPYRIDINE; AGING; EXCITOTOXICITY; N-METHYL-D-ASPARTATE; NEURODEGENERATION ID TOXIN 3-NITROPROPIONIC ACID; CEREBELLAR CLIMBING FIBERS; MITOCHONDRIAL; NIACINAMIDE; METABOLISM; HARMALINE; SYSTEM AB The effects of 3-acetylpyridine (3-AP) were studied in rat striatum. Striatal injections of 3-AP produced dose-dependent lesions. The lesion size was significantly increased in 4- and 12-month-old rats compared to 1-month-old rats. Coinjection of the competitive N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovaleric acid (APV) or systemic administration of the noncompetitive NMDA antagonist MK-801, the competitive NMDA antagonist LY274614, or the glutamate release inhibitor lamotrigine partially but significantly attenuated striatal lesion volume. Consistent with an NMDA receptor-mediated excitotoxic effect, histologic studies showed that 3-AP lesions result in relative sparing of NADPH-diaphorase neurons. Using freeze clamp, 3-AP resulted in a marked depletion of ATP. Two-dimensional water-suppressed proton chemical shift magnetic resonance imaging showed a striatal depletion of the neuronal marker N-acetylaspartate but no focal increase in lactate during the first 3 h after intrastriatal 3-AP injections. Pretreatment with fructose-l,6-biphosphate attenuated the lesion volume significantly, which may be due to its ability to serve as a substrate for glycolytic metabolism, with resulting ATP production. The results of the present studies support the hypothesis that 3-AP produces an impairment of energy metabolism due to its substitution for niacinamide in the formation of NAD(P). Furthermore, 3-AP toxicity may involve a secondary excitotoxic mechanism mediated by NMDA receptors. C1 MASSACHUSETTS GEN HOSP,WARREN 408,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MGH NMR CTR,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BEDFORD VA MED CTR,CTR GERIATR RES EDUC & CLIN,BEDFORD,MA. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. RI Schulz, Jorg/D-9786-2012; Kowall, Neil/G-6364-2012 OI Schulz, Jorg/0000-0002-8903-0593; Kowall, Neil/0000-0002-6624-0213 FU DS NIH HHS [NINDS 16367]; NINDS NIH HHS [NS 10828] NR 23 TC 26 Z9 26 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 1994 VL 14 IS 6 BP 1024 EP 1029 PG 6 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA PM721 UT WOS:A1994PM72100016 PM 7929644 ER PT J AU KEARSE, LA MAROTA, JJ AF KEARSE, LA MAROTA, JJ TI THE ROLE OF THE ELECTROENCEPHALOGRAM IN ASSESSING MEMORY FUNCTION UNDER GENERAL-ANESTHESIA SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material RP KEARSE, LA (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 NOV-DEC PY 1994 VL 6 IS 6 BP 457 EP 461 DI 10.1016/0952-8180(94)90084-1 PG 5 WC Anesthesiology SC Anesthesiology GA PX073 UT WOS:A1994PX07300001 PM 7880507 ER PT J AU KINSLEY, BT WIDOM, B UTZSCHNEIDER, K SIMONSON, DC AF KINSLEY, BT WIDOM, B UTZSCHNEIDER, K SIMONSON, DC TI STIMULUS SPECIFICITY OF DEFECTS IN COUNTERREGULATORY HORMONE-SECRETION IN INSULIN-DEPENDENT DIABETES-MELLITUS - EFFECT OF GLYCEMIC CONTROL SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOSE COUNTERREGULATION; SUBSEQUENT HYPOGLYCEMIA; RECURRENT HYPOGLYCEMIA; AUTONOMIC FAILURE; RESPONSES; PLASMA; IDDM; THRESHOLDS; SYMPTOMS; RADIOIMMUNOASSAY AB Counterregulatory hormone responses to hypoglycemia are impaired in subjects with insulin-dependent diabetes mellitus (IDDM) in strict glycemic control. To determine whether these defects are specific for hypoglycemia, we examined counterregulatory hormone responses during a 3-h hypoglycemic hyperinsulinemic clamp (14.4 pmol/kg.min) that lowered plasma glucose from 5.0 to 2.2 mmol/L in 9 well controlled IDDM patients (hemoglobin-Al, 7.5 +/- 0.8%), 9 poorly controlled patients (hemoglobin-Al, 12.5 +/- 1.5%), and 10 healthy volunteers. Counterregulatory hormone secretion was compared with responses to nonglucose secretagogues for epinephrine and norepinephrine (cold presser test), ACTH (overnight metyrapone test), and GH (L-arginine infusion). During hypoglycemia, epinephrine and cortisol responses were lower in the IDDM group in strict glycemic control than those in the poorly controlled IDDM group or healthy volunteers (P < 0.05). In response to the cold presser test, the areas under the curve for epinephrine and norepinephrine were also reduced in the well controlled IDDM group (P < 0.05 vs. healthy volunteers). The ACTH response to hypoglycemia was not significantly reduced in the well controlled IDDM, whereas the response to metyrapone was actually greater in this group (P < 0.05 us. poorly controlled IDDM). GH responses to both hypoglycemia and arginine were highest in the well controlled diabetic patients. These data suggest that 1) the reduced epinephrine responses in well controlled IDDM may not be specific for the hypoglycemic stimulus alone, but may also occur in response to other nonhypoglycemic stimuli; 2) cortisol responses to hypoglycemia are reduced in well controlled IDDM, whereas the ACTH response to a non-hypoglycemic stimulus remains intact; and 3) GH responses to both hypoglycemic and nonhypoglycemic stimuli are preserved in well controlled IDDM. The preservation of ACTH and GH responses to metyrapone and arginine, respectively, suggests adequate pituitary functional reserve in IDDM patients in strict glycemic control in response to nonhypoglycemic stimuli. C1 JOSLIN DIABET CTR, DEPT MED, BOSTON, MA 02215 USA. NEW ENGLAND DEACONESS HOSP, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK-36836] NR 46 TC 12 Z9 13 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 NOV PY 1994 VL 79 IS 5 BP 1383 EP 1389 DI 10.1210/jc.79.5.1383 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PT844 UT WOS:A1994PT84400027 PM 7962332 ER PT J AU LOBB, RR HEMLER, ME AF LOBB, RR HEMLER, ME TI THE PATHOPHYSIOLOGIC ROLE OF ALPHA-4 INTEGRINS IN-VIVO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID CELL-ADHESION MOLECULE-1; ALTERNATIVELY SPLICED DOMAIN; T-CELLS; LYMPHOCYTE MIGRATION; MONOCLONAL-ANTIBODY; VLA-4 INTEGRIN; BINDING-SITE; TYROSINE PHOSPHORYLATION; ANTI-ALPHA-4 INTEGRIN; CYTOPLASMIC DOMAINS C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP LOBB, RR (reprint author), BIOGEN INC,14 CAMBRIDGE CTR,CAMBRIDGE,MA 02142, USA. FU NIGMS NIH HHS [GM-38903, GM-46526] NR 97 TC 327 Z9 332 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1994 VL 94 IS 5 BP 1722 EP 1728 DI 10.1172/JCI117519 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PQ941 UT WOS:A1994PQ94100004 PM 7525645 ER PT J AU GANJU, RK SUNDAY, M TSARWHAS, DG CARD, A SHIPP, MA AF GANJU, RK SUNDAY, M TSARWHAS, DG CARD, A SHIPP, MA TI CD1O/NEP IN NONSMALL-CELL-LUNG CARCINOMAS - RELATIONSHIP TO CELLULAR PROLIFERATION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE COMMON ACUTE LYMPHOBLASTIC LEUKEMIA ANTIGEN; NONSMALL CELL LUNG CARCINOMAS; PROLIFERATING CELL NUCLEAR ANTIGEN; PEPTIDE GROWTH FACTORS; GROWTH REGULATION ID NEUTRAL ENDOPEPTIDASE 24.11; BOMBESIN-LIKE PEPTIDES; GASTRIN-RELEASING PEPTIDE; LEUKEMIA ANTIGEN CALLA; CASEIN KINASE-II; HUMAN-FETAL LUNG; NEUROMEDIN-B; GUINEA-PIG; CHROMOSOMAL LOCALIZATION; MOLECULAR-CLONING AB The cell surface metalloproteinase CD10/neutral endopeptidase 24.11 (NEP) hydrolyzes a variety of peptide substrates and reduces cellular responses to specific peptide hormones. Because CD10/NEP modulates peptide-mediated proliferation of small cell carcinomas of the lung (SCLC) and normal fetal bronchial epithelium, we evaluated the enzyme's expression in non-small cell lung carcinomas (NSCLC). Bronchoalveolar and large cell carcinoma cell lines had low levels of CD10/NEP expression whereas squamous, adenosquamous, and adenocarcinoma cell lines had higher and more variable levels of the cell surface enzyme. Regional variations in CD10/NEP immunostaining in primary NSCLC specimens prompted us to correlate CD10/NEP expression with cell growth. In primary carcinomas of the lung, clonal NSCLC cell lines and SV40-transformed fetal airway epithelium, subsets of cells expressed primarily CD10/NEP or the proliferating cell nuclear antigen (PCNA). Cultured airway epithelial cells had the lowest levels of CD10/NEP expression when the highest percentage of cells were actively dividing; in addition, these cells grew more rapidly when cell surface CD10/NEP was inhibited. NSCLC cell lines had receptors for a variety of mitogenic peptides known to be CD10/NEP substrates, underscoring the functional significance of growth-related variability in CD10/NEP expression. C1 DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 53 TC 47 Z9 47 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1994 VL 94 IS 5 BP 1784 EP 1791 DI 10.1172/JCI117526 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PQ941 UT WOS:A1994PQ94100011 PM 7962523 ER PT J AU COOPER, JB AF COOPER, JB TI APSF SUPPORTS ANALYSIS OF AIMS DATA SO JOURNAL OF CLINICAL MONITORING LA English DT Article ID 2000 INCIDENT REPORTS RP COOPER, JB (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA 02114, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0748-1977 J9 J CLIN MONITOR JI J. Clin. Monit. PD NOV PY 1994 VL 10 IS 6 BP 425 EP 426 DI 10.1007/BF01618429 PG 2 WC Anesthesiology SC Anesthesiology GA PR229 UT WOS:A1994PR22900017 PM 7836982 ER PT J AU KANTOFF, PW TALCOTT, JA AF KANTOFF, PW TALCOTT, JA TI THE RADICAL PROSTATECTOMY SERIES - APPLES ARE NOT ORANGES SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CANCER; RADIOTHERAPY; TRENDS RP KANTOFF, PW (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1994 VL 12 IS 11 BP 2243 EP 2245 PG 3 WC Oncology SC Oncology GA PP880 UT WOS:A1994PP88000002 PM 7964938 ER PT J AU ROTH, BJ DREICER, R EINHORN, LH NEUBERG, D JOHNSON, DH SMITH, JL HUDES, GR SCHULTZ, SM LOEHRER, PJ AF ROTH, BJ DREICER, R EINHORN, LH NEUBERG, D JOHNSON, DH SMITH, JL HUDES, GR SCHULTZ, SM LOEHRER, PJ TI SIGNIFICANT ACTIVITY OF PACLITAXEL IN ADVANCED TRANSITIONAL-CELL CARCINOMA OF THE UROTHELIUM - A PHASE-II TRIAL OF THE EASTERN-COOPERATIVE-ONCOLOGY-GROUP SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; M-VAC METHOTREXATE; INFUSION GALLIUM NITRATE; RADIATION SENSITIZER; BLADDER-CARCINOMA; RANDOMIZED TRIAL; URINARY-TRACT; LUNG-CANCER; CISPLATIN; DOXORUBICIN AB Purpose: To assess the efficacy and toxicity of single-agent paclitaxel as first-line chemotherapy in patients with locally advanced or mel astatic transitional-cell carcinoma of the urothelium. Patients end Methods: Twenty-six eligible patients were enrolled onto this cooperative group study and treated with paclitaxel at a dosage of 250 mg/m(2) by 24-hour continuous infusion every 21 days until progression or patient intolerance. All patients received recombinant human granulocyte colony-stimulating factor (rhG-CSF) at 5 mu g/kg/d for at least 10 days during each cycle. Results: Eleven of 26 patients (42%; 95% confidence interval [CI], 23% to 63%) demonstrated an objective response, with seven achieving a complete clinical response (CR) (27%; 95% CI, 12% to 48%) and four (15%) a partial response (PR). The median duration of response in the 11 responders is 7+ months (range, 4 to 17), with five responders (four CRs, one PR) remaining progression-free at 5, 6, 10, 12, and 16 months from the start of therapy. The estimated median survival duration for all patients is 8.4 months. Hematologic toxicity consisted of anemia (12% grade 3) and granulocytopenia (4% grade 3, 19% grade 4), with two patients developing granulocytopenic fevers. Nonhematologic toxicity included grade 3 mucositis in 11%, grade 3 neuropathy in 11%, and grade 4 diarrhea in 4%. Conclusion: Single-agent paclitaxel at this dosage and schedule is one of the most active single agents in previously untreated patients with advanced urothelial carcinoma, and is well tolerated by this patient population when given with hematopoetic growth factor support. (C) 1994 by American Society of Clinical Oncology. C1 INDIANA UNIV,MED CTR,DIV HEMATOL ONCOL,INDIANAPOLIS,IN. METHODIST HOSP INDIANA,COMMUNITY CLIN ONCOL PROGRAM,INDIANAPOLIS,IN 46202. UNIV IOWA,IOWA CITY,IA. DANA FARBER CANC INST,DIV BIOSTAT,CTR STAT,EASTERN COOPERAT ONCOL GRP,BOSTON,MA. VANDERBILT UNIV,NASHVILLE,TN. UNIV ROCHESTER,ROCHESTER,NY. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA21115, CA49883, CA49957] NR 45 TC 264 Z9 265 U1 0 U2 4 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 NOV PY 1994 VL 12 IS 11 BP 2264 EP 2270 PG 7 WC Oncology SC Oncology GA PP880 UT WOS:A1994PP88000006 PM 7525883 ER PT J AU CANELLOS, GP AF CANELLOS, GP TI ASCO 30 YEARS LATER - THE STATE OF THE SOCIETY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 DANA FARBER CANC INST,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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1994 VL 12 IS 11 BP 2510 EP 2513 PG 4 WC Oncology SC Oncology GA PP880 UT WOS:A1994PP88000036 PM 7964966 ER PT J AU MORENO, EC KRESAK, M GAFFAR, A AF MORENO, EC KRESAK, M GAFFAR, A TI ADSORPTION OF PEROXYDIPHOSPHATE ONTO HYDROXYAPATITE - KINETICS, THERMODYNAMICS, AND CRYSTAL-GROWTH INHIBITION SO JOURNAL OF COLLOID AND INTERFACE SCIENCE LA English DT Article ID HUMAN SALIVARY PROTEINS; CALCIUM APATITES; POTASSIUM PEROXYDIPHOSPHATE; PRECIPITATION; PYROPHOSPHATE; PHOSPHONATES; PHOSPHATE; FLUORIDE; ACIDS AB Peroxydiphosphate ion, P2O84-, PDP, a potential agent to control mineralization in biological systems, adsorbs readily onto hydroxyapatite, HA, the prototype of the mineral in bones and teeth. The apatite crystals, however, catalyze the hydrolysis of PDP, which is faster at 37 degrees C than at 4 degrees C. Hydrolysis at the lower temperature is a first order reaction; at 37 degrees C the process is more complex and may be limited by surface diffusion. Orthophosphate in solution represses the hydrolysis of PDP. Adsorption isotherms were determined in the presence of orthophosphate at the two temperatures mentioned. The experimental data were best described by a model involving two adsorption sites at which PDP adsorbs in competition with orthophosphate ions. The adsorption bond at one of the sites is more than 10 times stronger but its capacity is from 1/4 (at 37 degrees) to 1/8 (at 4 degrees) the capacity of the site displaying the weaker bond. The inhibition of crystal growth by PDP is related only to its adsorption onto one of the adsorption sites, which represents only 18% of the maximal PDP adsorption. It is inferred that crystal growth occurs (or is initiated) on a relatively small fraction of the crystal surface. Calculation of the thermodynamic functions for adsorption shows that the reaction is endothermic and, therefore, that adsorption of PDP is entropically driven; the gain in entropy is probably associated with changes in the location of water molecules on the adsorbate and the adsorbent. The reported thermodynamic properties of the two adsorption sites are distinctly different. (C) 1994 Academic Press, Inc. C1 COLGATE PALMOLIVE CO,CORP TECHNOL CTR,PISCATAWAY,NJ 08854. RP MORENO, EC (reprint author), FORSYTH DENT CTR,DEPT PHYS CHEM,140 FENWAY,BOSTON,MA 02115, USA. NR 30 TC 11 Z9 11 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0021-9797 J9 J COLLOID INTERF SCI JI J. Colloid Interface Sci. PD NOV PY 1994 VL 168 IS 1 BP 173 EP 182 DI 10.1006/jcis.1994.1406 PG 10 WC Chemistry, Physical SC Chemistry GA PN462 UT WOS:A1994PN46200021 ER PT J AU KOBLER, JB DATTA, S GOYAL, RK BENECCHI, EJ AF KOBLER, JB DATTA, S GOYAL, RK BENECCHI, EJ TI INNERVATION OF THE LARYNX, PHARYNX, AND UPPER ESOPHAGEAL SPHINCTER OF THE RAT SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE MOTOR NEURON; VAGUS NERVE; DEGLUTITION; BRAIN-STEM; DYSPHAGIA ID NUCLEUS AMBIGUUS MOTONEURONS; UPPER ALIMENTARY-TRACT; VAGUS NERVE; HORSERADISH-PEROXIDASE; AFFERENT COMPONENTS; CONSTRICTOR MUSCLES; ANATOMICAL EVIDENCE; MOTO-NEURONS; EFFERENT; CAT AB We identified a 'semicircular' compartment of the rat thyropharyngeus muscle at the pharyngoesophageal junction and used the glycogen depletion method to determine how the fibers of this muscle (as well as all others of the pharynx and larynx) are innervated by different cranial nerve branches. The semicircular compartment appears anatomically homologous to the human cricopharyngeus muscle, an important component of the upper esophageal sphincter. While we found very little overlap in the muscle targets of the pharyngeal, superior laryngeal and recurrent laryngeal nerves within the pharynx and larynx, the semicircular muscle receives a dual, interdigitating innervation from two vagal branches: the pharyngeal nerve and a branch of the superior laryngeal nerve we call the dorsal accessory branch. After applying horseradish peroxidase to either of these two nerves, we compared the distribution and number of cells labeled in the brainstem. The dorsal accessory branch conveys a more heterogeneous set of efferent fibers than does the pharyngeal nerve, including the axons of pharyngeal and esophageal motor neurons and parasympathetic preganglionic neurons. The observed distribution of labeled motor neurons in nucleus ambiguus also leads us to suggest that the semicircular compartment is innervated by two subsets of motor neurons, one of which is displaced ventrolateral to the main pharyngeal motor column. This arrangement raises the possibility of functional differences among semicircular compartment motor neurons correlated with the observed differences in brainstem location of cell bodies. (C) 1994 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT GASTROENTEROL,BOSTON,MA 02115. RP KOBLER, JB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,HARRIS PEYTON MOSHER LARYNGOL RES LAB,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC0129]; NIDDK NIH HHS [DK-31092] NR 52 TC 35 Z9 35 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 1 PY 1994 VL 349 IS 1 BP 129 EP 147 DI 10.1002/cne.903490109 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA PM876 UT WOS:A1994PM87600008 PM 7852622 ER PT J AU HALAVAARA, JT LAMMINEN, AE BONDESTAM, S STANDERTSKJOLDNORDENSTAM, CG HAMBERG, LM AF HALAVAARA, JT LAMMINEN, AE BONDESTAM, S STANDERTSKJOLDNORDENSTAM, CG HAMBERG, LM TI DETECTION OF FOCAL LIVER-LESIONS WITH SUPERPARAMAGNETIC IRON-OXIDE - VALUE OF STIR AND SE IMAGING SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE MAGNETIC RESONANCE IMAGING; CONTRAST MEDIA; SUPERPARAMAGNETIC IRON OXIDE; LIVER, NEOPLASMS ID CONTRAST AGENT; CLINICAL-APPLICATION; HEPATIC METASTASES; COLORECTAL-CANCER; PULSE SEQUENCE; FIELD-STRENGTH; MR IMAGES; CT; DIFFERENTIATION; PORTOGRAPHY AB Objective: We assessed the value of superparamagnetic iron oxide (SPIO) particles on the detection of focal liver lesions by MRI. Materials and Methods: Twenty patients with one to five focal liver lesions, primarily detected with ultrasonography and/or contrast-enhanced CT, were evaluated further with unenhanced and iron oxide-enhanced MRI at 1.0 T. Superparamagnetic iron oxide particles were administered intravenously as a slow infusion. Then T1-, T2-, and proton density-weighted SE images were obtained. In addition, the performance of a short TI inversion recovery (STIR) sequence was evaluated. Results: The iron oxide contrast medium had marked effects on liver signal-to-noise (S/N) and tumor-to-liver contrast-to-noise (C/N) ratios but only minimal effects on tumor S/N ratios in cases of malignant tumor foci. Lesion-to-liver contrast, expressed as differences between the tumor and liver S/N ratios, improved very significantly after SPIO infusion with all four pulse sequences. Contrast enhancement of the liver parenchyma was best in T2-weighted SE images, but the tumor-to-liver C/N values were highest with the postcontrast STIR sequence. The SPIO enhancement revealed a number of additional focal lesions (31%), also foci under 1 cm in diameter. In three benign focal lesions, SPIO infusion produced a definite reduction in the S/N ratio of the lesions in contrast to the minimal change measured in malignant foci. The favorable performance of the STIR sequence contradicts the disappointing results previously obtained at 0.6 T. Conclusion: Superparamagnetic iron oxide is a promising new contrast medium for MR examinations of the liver, increasing the conspicuity and reducing the detectability threshold of focal hepatic lesions. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA. RP HALAVAARA, JT (reprint author), UNIV HELSINKI,CENT HOSP,DEPT RADIOL,HAARTMANINKATU 4,SF-00290 HELSINKI,FINLAND. NR 26 TC 35 Z9 35 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 1994 VL 18 IS 6 BP 897 EP 904 DI 10.1097/00004728-199411000-00009 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PQ946 UT WOS:A1994PQ94600009 PM 7962796 ER PT J AU HAY, DI AHERN, JM SCHLUCKEBIER, SK SCHLESINGER, DH AF HAY, DI AHERN, JM SCHLUCKEBIER, SK SCHLESINGER, DH TI HUMAN SALIVARY ACIDIC PROLINE-RICH PROTEIN POLYMORPHISMS AND BIOSYNTHESIS STUDIED BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE SALIVA; SALIVARY PROTEINS; PROLINE-RICH PROTEINS; GENE EXPRESSION; POSTTRANSLATIONAL PROCESSING ID HUMAN-PAROTID SALIVA; APATITIC SURFACES; GENETIC-POLYMORPHISM; PHOSPHOPROTEIN; STATHERIN; PIF; PURIFICATION; ADSORPTION; SECRETIONS; ADHESION AB Human salivary acidic proline-rich proteins (PRPs) constitute a significant fraction of the total salivary protein and possess important biological activities. Different genetic and post-translationally processed forms of the PRPs exhibit significant quantitative variations in several of these activities, especially the modulation of salivary calcium phosphate chemistry and oral bacterial adhesion. To quantify and understand these differences, we have developed a high-performance liquid chromatography (HPLC) method to identify and measure individual PRPs in saliva. The data obtained permit the identification of PRP polymorphisms and phenotypes, the determination of the relative amounts of PRPs derived from the two loci, PRH1 and PRH2, and the measurement of the extent of post-translational cleavage of the primary polypeptide products. Substantial inter-gland and interindividual variations were found in relative amounts of PRPs derived from the two loci (at least two-fold), and in post-translational cleavage (greater than two-fold), both of which are likely to be biologically significant. Also in this study, the presence of what appear to be minor amounts of numerous variant PRPs in glandular secretions was observed, and two uncommon PRP polymorphisms were identified in the 127 subjects studied. C1 NYU,MED CTR,DEPT MED,NEW YORK,NY 10016. NYU,MED CTR,DEPT CELL BIOL,NEW YORK,NY 10016. RP HAY, DI (reprint author), FORSYTH DENT CTR,DEPT BIOCHEM,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-3915, DE-6159, DE-7009] NR 47 TC 43 Z9 43 U1 0 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 1994 VL 73 IS 11 BP 1717 EP 1726 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PW796 UT WOS:A1994PW79600007 PM 7983258 ER PT J AU VANHOUTE, J LOPMAN, J KENT, R AF VANHOUTE, J LOPMAN, J KENT, R TI THE PREDOMINANT CULTIVABLE FLORA OF SOUND AND CARIOUS HUMAN ROOT SURFACES SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE HUMAN ROOT SURFACE; PREDOMINANT ROOT BACTERIA; PLAQUE; MUTANS STREPTOCOCCI; NON-MUTANS STREPTOCOCCI ID STREPTOCOCCUS-MUTANS; MICROBIAL-FLORA; DENTAL PLAQUE; SP-NOV; CARIES; ASSOCIATION; BACTEROIDES; POPULATION; MICROFLORA; BACTERIA AB Little detailed knowledge exists about the composition of the human root flora. Therefore, the predominant cultivable flora (PCF) was determined for samples of: (1) plaque from sound root surfaces (SRS) in eight subjects without root caries, (2) plaque from incipient root lesions (IRL) in eight subjects with root caries, and (3) carious material from advanced root lesions (ARL) in nine other subjects with rest caries. Generally, one root surface was sampled per subject, and organisms-358, 512, and 389 for SRS, IRL, and ARL, respectively-were identified by standard methods. It was found that: (1) streptococci, actinomyces, and veillonellae constituted 84.2, 57.8, and 65.7% of the PCF of SRS, IRL, and ARL samples, respectively; (2) a wide variety of other Gram-positive cocci and Gram-positive and -negative rods was also present; (3) the PCF of many samples was often dominated by few organisms, the identity of which differed from sample to sample; (4) a negative and no association with root caries existed for the PCF levels of the non-mutans streptococci (non-MS) and the actinomyces; and ((5) mutans streptococci (MS) and lactobacilli (L) were not always present among the PCF of IRL and ARL, respectively, and non-MS were isolated from the PCF of most lesions and actinomyces from all lesions. Our findings illustrate the complexity of the root surface flora and suggest that root caries development involves organisms other than MS and L. C1 FORSYTH DENT CTR,DEPT CLIN TRIALS & EXPERIMENTAT,BOSTON,MA 02115. RP VANHOUTE, J (reprint author), FORSYTH DENT CTR,DEPT ORAL MICROBIOL,140 THE FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE07009] NR 27 TC 73 Z9 74 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 1994 VL 73 IS 11 BP 1727 EP 1734 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PW796 UT WOS:A1994PW79600008 PM 7983259 ER PT J AU BOUSSIOTIS, VA FREEMAN, GJ GRIFFIN, JD GRAY, GS GRIBBEN, JG NADLER, LM AF BOUSSIOTIS, VA FREEMAN, GJ GRIFFIN, JD GRAY, GS GRIBBEN, JG NADLER, LM TI CD2 IS INVOLVED IN MAINTENANCE AND REVERSAL OF HUMAN ALLOANTIGEN-SPECIFIC CLONAL ANERGY SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL ACTIVATION; CTLA-4 COUNTER-RECEPTOR; HUMAN LYMPHOCYTES-T; COSTIMULATORY SIGNAL; MONOCLONAL-ANTIBODY; ANTIGEN; LIGAND; INDUCTION; B7; INTERLEUKIN-2 AB Induction and maintenance of a state of T cell unresponsiveness to specific alloantigen would have significant implications for human organ transplantation. Using human histocompatibility leukocyte antigen DR7-specific helper T cell clones, we demonstrate that blockade of the B7 family of costimulatory molecules is sufficient to induce alloantigen-specific T cell clonal anergy. Anergized cells do not respond to alloantigen and a variety of costimulatory molecules, including B7-1, B7-2, intercellular adhesion moleculel-1 (ICAM-1), and lymphocyte function-associated molecule (LFA)-3. However, after culture in exogenous interleukin (IL)-2 for at least 7 d, anergized cells can respond to alloantigen in the presence of LFA-3. LFA-3 costimulation subsequently restores responsiveness to alloantigen in the presence of previously insufficient costimulatory signals. Expression of CD2R epitope is downregulated on anergic cells and is restored after 7 d of IL-2 culture. The loss of the CD2R is temporally associated with the inability of anergized cells to respond to LFA-3. These results suggest that in addition to blockade of B7 family members, inhibition of CD2 and, potentially, other costimulatory pathways that might reverse anergy will be necessary to maintain prolonged alloantigen-specific tolerance. C1 REPLIGEN CORP,CAMBRIDGE,MA 02139. RP BOUSSIOTIS, VA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HEMATOL MALIGNANCIES,DANA 740,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-34183, CA-40416] NR 53 TC 109 Z9 111 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1994 VL 180 IS 5 BP 1665 EP 1673 DI 10.1084/jem.180.5.1665 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PP543 UT WOS:A1994PP54300010 PM 7525835 ER PT J AU ARULANANDAM, ARN KISTER, A MCGREGOR, MJ WYSS, DF WAGNER, G REINHERZ, EL AF ARULANANDAM, ARN KISTER, A MCGREGOR, MJ WYSS, DF WAGNER, G REINHERZ, EL TI INTERACTION BETWEEN HUMAN CD2 AND CD58 INVOLVES THE MAJOR BETA-SHEET SURFACE OF EACH OF THEIR RESPECTIVE ADHESION DOMAINS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL ACTIVATION; FUNCTION-ASSOCIATED ANTIGEN-3; HUMAN LYMPHOCYTES-T; RED BLOOD-CELLS; ERYTHROCYTE RECEPTOR; MOLECULAR-CLONING; ALTERNATIVE PATHWAY; SIGNAL TRANSDUCTION; CRYSTAL-STRUCTURE; LARGE POPULATION AB The CD58 binding site on human CD2 was recently shown by nuclear magnetic resonance structural data in conjunction with site-directed mutagenesis to be a highly charged surface area covering similar to 770 Angstrom(2) on the major AGFCC'C'' face of the CD2 immunoglobulin-like (Ig-like) NH2-terminal domain. Here we have identified the other binding surface of the CD2-CD58 adhesion pair by mutating charged residues shared among CD2 ligands (human CD58, sheep CD58, and human CD48) that are predicted to be solvent exposed on a molecular model of the Ig-like adhesion domain of human CD58. This site includes beta strand residues along the C strand (E25, K29, and K30), in the middle of the C' strand (E37) and in the G strand (K87). In addition, several residues on the CC' loop (K32, D33, and K34) form this site. Thus, the interaction between CD2 and CD58 involves the major beta sheet surface of each adhesion domain. Possible docking orientations for the CD2-CD58 molecular complex are offered. Strict conservation of human and sheep CD58 residues within the involved C and C' strands and CC' loop suggests that this region is particularly important for stable formation of the CD2-CD58 complex. The analysis of this complex offers molecular insight into the nature of a receptor-ligand pair involving two Ig family members. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. PROCEPT INC,CAMBRIDGE,MA 02139. RP ARULANANDAM, ARN (reprint author), DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02135, USA. FU NIAID NIH HHS [AI-21226]; NIGMS NIH HHS [GM-38608] NR 57 TC 41 Z9 42 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1994 VL 180 IS 5 BP 1861 EP 1871 DI 10.1084/jem.180.5.1861 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PP543 UT WOS:A1994PP54300028 PM 7525842 ER PT J AU LEONG, GB SILVA, JA GARZATREVINO, ES OLIVA, D FERRARI, MM KOMANDURI, RV CALDWELL, JCB AF LEONG, GB SILVA, JA GARZATREVINO, ES OLIVA, D FERRARI, MM KOMANDURI, RV CALDWELL, JCB TI THE DANGEROUSNESS OF PERSONS WITH THE OTHELLO SYNDROME SO JOURNAL OF FORENSIC SCIENCES LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Academy-of-Forensic-Sciences CY FEB 14-19, 1994 CL SAN ANTONIO, TX SP AMER ACAD FORENSIC SCI DE PSYCHIATRY; DANGEROUSNESS; DELUSIONS; MENTAL DISORDER; OTHELLO SYNDROME; ORGANIC DELUSIONAL DISORDER ID PATHOLOGICAL JEALOUSY; MORBID JEALOUSY; SEXUAL JEALOUSY; PIMOZIDE; FLUOXETINE AB The Othello syndrome, or delusional jealousy, often raises significant forensic issues, particularly dangerousness. Dangerous patients suffering from the Othello delusion may present with hostility ranging from verbal threats to homicidal acts. We present three cases of individuals suffering from Othello syndrome associated with significant hostility and organic mental factors. We analyze these cases along with Othello syndrome cases culled from the recent anglophonic literature, especially in terms of implications for domestic and public safety. C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. RP LEONG, GB (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV 116AA,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 35 TC 12 Z9 13 U1 0 U2 4 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 NOV PY 1994 VL 39 IS 6 BP 1445 EP 1454 PG 10 WC Medicine, Legal SC Legal Medicine GA PV998 UT WOS:A1994PV99800012 PM 7815024 ER PT J AU SILVA, JA LEONG, GB GARZATREVINO, ES LEGRAND, J OLIVA, D WEINSTOCK, R BOWDEN, CL AF SILVA, JA LEONG, GB GARZATREVINO, ES LEGRAND, J OLIVA, D WEINSTOCK, R BOWDEN, CL TI A COGNITIVE MODEL OF DANGEROUS DELUSIONAL MISIDENTIFICATION SYNDROMES SO JOURNAL OF FORENSIC SCIENCES LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Academy-of-Forensic-Sciences CY FEB 14-19, 1994 CL SAN ANTONIO, TX SP AMER ACAD FORENSIC SCI DE PSYCHIATRY; DANGEROUSNESS; VIOLENCE; DELUSIONS; MISIDENTIFICATION; MENTAL DISORDER ID CAPGRAS SYNDROME; SUBJECTIVE DOUBLES; PREFRONTAL CORTEX; FREGOLI SYNDROME; SCHIZOPHRENIA; VIOLENCE; INTERMETAMORPHOSIS; PERSPECTIVE; EROTOMANIA; TOMOGRAPHY AB The hallmark of the delusional misidentification syndromes is the presence of a misidentification delusion of the self or others. Delusional misidentification may present with an increased risk for dangerous behaviors. Individuals suffering from delusional misidentification syndromes may express hostility in ways ranging from serious verbal threats to homicidal acts. The causes of dangerous misidentification delusions remain for the most part undetermined. In this article, we report a series of six cases of individuals who harbored dangerous misidentification delusions. These individuals were studied phenomenologically and forensically. They were also studied biologically, including neuropsychological testing. A cognitive hypothesis aimed at explaining dangerousness and delusional misidentification is proposed. Implications of the hypothesis for further research are briefly outlined. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP SILVA, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV 116A,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 64 TC 14 Z9 14 U1 1 U2 7 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 NOV PY 1994 VL 39 IS 6 BP 1455 EP 1467 PG 13 WC Medicine, Legal SC Legal Medicine GA PV998 UT WOS:A1994PV99800013 PM 7815025 ER PT J AU LIVINGSTON, EH AF LIVINGSTON, EH TI BLOOD-FLOW, CONTRACTIONS AND ISCHEMIA-REPERFUSION - A POSSIBLE PATHOGENETIC MECHANISM FOR ULCERS SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID INDUCED GASTRIC-LESIONS; MUCOSAL INJURY; RAT; ACID; DISTENSION; ISCHEMIA; MOTILITY; STOMACH; DAMAGE C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,SURG SERV,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,RES SERV,LOS ANGELES,CA. CTR ULCER RES & EDUC,LOS ANGELES,CA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL AUSTR PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON 3053, AUSTRALIA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD NOV-DEC PY 1994 VL 9 IS 6 BP 652 EP 653 DI 10.1111/j.1440-1746.1994.tb01580.x PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PY131 UT WOS:A1994PY13100026 PM 7865728 ER PT J AU BISCHOFF, R BUECHLER, U DEROCHE, R JUPITER, J AF BISCHOFF, R BUECHLER, U DEROCHE, R JUPITER, J TI CLINICAL-RESULTS OF TENSION BAND FIXATION OF AVULSION FRACTURES OF THE HAND SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB We report 100 cases in which a tension-band technique was used to secure fixation of avulsion fractures with in the digits. Included are 51 bony mallet fractures that were subluxed or irreducible, 38 displaced bony gamekeeper's fractures of the thumb, 8 fractures of the lateral phalangeal base, and 3 avulsion fractures that involved the base of the dorsal aspect of the middle phalanx. We evaluated results on the basis of clinical and x-ray film criteria. Excellent or satisfactory results were found in all 38 bony gamekeeper's injuries. All but one gamekeeper's fracture healed; the one nonunion was asymptomatic. All eight patients with lateral avulsion fractures had an excellent or satisfactory result on clinical examination. Seven of the eight had an excellent result on x-ray film evaluation; the one malnuion was asymptomatic. Two of the three fractures with dorsal avulsions of the base of the middle phalanx had a satisfactory result on clinical and x-ray film examination; the one poor result was due to the severity of the comminution of the fracture. However, 21 of the 51 bony mallet injuries had a poor result both clinically and radiographically. We noted numerous postoperative complications including dorsal skin breakdown, superficial and deep infection, and secondary displacement of the fragment. Tension-band fixation is an excellent method for treating various avulsion fractures of the hand such as bony gamekeeper's thumb, lateral avlusion injuries, and dorsal avulsions of the middle phalanx. However, the treatment of bony mallet fingers with tension band fixation is less predictable and should be used with caution. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ORTHOPAED,HAND SURG SERV,BOSTON,MA 02114. NR 0 TC 45 Z9 48 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 1994 VL 19A IS 6 BP 1019 EP 1026 DI 10.1016/0363-5023(94)90109-0 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PT191 UT WOS:A1994PT19100024 PM 7876474 ER PT J AU KRUEGER, GG MORGAN, JR JORGENSEN, CM SCHMIDT, L LI, HL KWAN, MK BOYCE, ST WILEY, HS KAPLAN, J PETERSEN, MJ AF KRUEGER, GG MORGAN, JR JORGENSEN, CM SCHMIDT, L LI, HL KWAN, MK BOYCE, ST WILEY, HS KAPLAN, J PETERSEN, MJ TI GENETICALLY-MODIFIED SKIN TO TREAT DISEASE - POTENTIAL AND LIMITATIONS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID MEDIATED GENE-TRANSFER; EPIDERMAL-KERATINOCYTES; GROWTH-HORMONE; P53 MUTATIONS; THERAPY; FIBROBLASTS; MICE; TRANSPLANTATION; EXPRESSION; GRAFTS AB Molecular definition of disease at the level of the gene and advances in recombinant DNA technology suggest that many diseases are amenable to correction by genes not bearing the defective elements that result in disease. Many questions must be answered before this therapy can be used to correct chronic diseases. These questions fall into safety and efficacy categories. Experience with transplanting cellular elements of skin or skin substitutes (defined as skin that possess the cell types and a dermal structure to develop into a functioning skin) to athymic rodents is considerable and is seen as a system where these questions can be answered. This paper reviews these questions and presents our early analysis of genetically modified cells in skin substitutes in vivo and in vitro. Experimental data demonstrate that both a matrix of woven nylon, housing a fibroblast generated collage, and dead dermis can be utilized to shuttle genetically modified human fibroblasts from the laboratory to an in vivo setting. Genetically modified fibroblasts do not migrate from the shuttle to the surrounding tissue. The survival of significant numbers, similar to 70%, of genetically modified fibroblasts for at least 6 weeks in these shuttles, supports this general approach as having clinical utility. It is also concluded that skin substitute systems can be used to generate a genetically modified skin in vitro that has the capacity to develop into functional skin in vivo. Further, as genetically modified keratinocytes differentiate there is increased production by the transgene, supporting the concept that keratinocytes have true potential as shuttles for therapeutic genes. This work demonstrates that transplantation of systems containing genetically modified cells of the skin can be used to experimentally define many aspects of gene therapy using skin before this technology is taken to the clinic. Examples include determining the effect of gene transduction and expression on structure and function of the genetically modified skin as well as on distant skin and an assessment of the translational capacity of the transgene as function of time and cell number. C1 UNIV UTAH, HLTH SCI CTR, DEPT PATHOL, DIV EXPTL PATHOL, SALT LAKE CITY, UT 84132 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, SHRINERS BURNS INST,SURG SERV, BOSTON, MA USA. DEPT BIOENGN, LA JOLLA, CA USA. UNIV CINCINNATI, SHRINERS BURNS INST, CINCINNATI, OH USA. UNIV CINCINNATI, DEPT SURG, CINCINNATI, OH 45267 USA. RP KRUEGER, GG (reprint author), UNIV UTAH, HLTH SCI CTR, DEPT MED, DIV DERMATOL, SALT LAKE CITY, UT 84132 USA. NR 46 TC 51 Z9 52 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1994 VL 103 IS 5 SU S BP S76 EP S84 DI 10.1111/1523-1747.ep12399100 PG 9 WC Dermatology SC Dermatology GA PU666 UT WOS:A1994PU66600014 PM 7963689 ER PT J AU KIEBURTZ, K MACDONALD, M SHIH, C FEIGIN, A STEINBERG, K BORDWELL, K ZIMMERMAN, C SRINIDHI, J SOTACK, J GUSELLA, J SHOULSON, I AF KIEBURTZ, K MACDONALD, M SHIH, C FEIGIN, A STEINBERG, K BORDWELL, K ZIMMERMAN, C SRINIDHI, J SOTACK, J GUSELLA, J SHOULSON, I TI TRINUCLEOTIDE REPEAT LENGTH AND PROGRESSION OF ILLNESS IN HUNTINGTONS-DISEASE SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID AGE-OF-ONSET; FEATURES; MUTATION AB The genetic defect causing Huntington's disease (HD) has been identified as an unstable expansion of a trinucleotide (CAG) repeat sequence within the coding region of the IT15 gene on chromosome 4. In 50 patients with manifest HD who were evaluated prospectively and uniformly, we examined the relationship between the extent of the DNA expansion and the rate of illness progression. Although the length of CAG repeats showed a strong inverse correlation with the age at onset of HD, there was no such relationship between the number of CAG repeats and the rate of clinical decline. These findings suggest that the CAG repeat length may influence or trigger the onset of HD, but other genetic, neurobiological, or environmental factors contribute to the progression of illness and the underlying pace of neuronal degeneration. C1 MASSACHUSETTS GEN HOSP,NEUROGENET UNIT,BOSTON,MA 02114. RP KIEBURTZ, K (reprint author), UNIV ROCHESTER,MED CTR,DEPT NEUROL,BOX 673,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NCRR NIH HHS [RR-00044]; NINDS NIH HHS [NS-16367, NS-17978] NR 15 TC 86 Z9 86 U1 0 U2 8 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 1994 VL 31 IS 11 BP 872 EP 874 DI 10.1136/jmg.31.11.872 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA PQ129 UT WOS:A1994PQ12900011 PM 7853373 ER PT J AU TIMOFEEV, BA BOLOTIN, IM STEPANOVA, LP BOGDANOV, AA GEORGIU, K MALYSHEV, SN PETROVSKY, VV KLIBANOV, AL TORCHILIN, VP AF TIMOFEEV, BA BOLOTIN, IM STEPANOVA, LP BOGDANOV, AA GEORGIU, K MALYSHEV, SN PETROVSKY, VV KLIBANOV, AL TORCHILIN, VP TI LIPOSOMAL DIAMIDINE (IMIDOCARB) - PREPARATION AND ANIMAL STUDIES SO JOURNAL OF MICROENCAPSULATION LA English DT Article AB Diamidine (imidocarb, 3,3'-di-imidasolin-2-yl carbonylide dihydrochloride), a babesicidal drug, was encapsulated in liposomes to reduce the toxicity of the drug and to increase its therapeutic index. Liposomes were prepared from the mixture of egg yolk phosphatidyl choline and cholesterol (1:1 molar ratio) by a reverse-phase evaporation technique. Liposomes used in the study were of diameter 1.5-2.5 mum and contained 53 mg/ml (0.125 M) of diamidine. Animal tests were performed in three animal species. The LD50 values of the liposome-encapsulated diamidine administered intravenously and intramuscularly in inbred white mice were 52 and 6000mg/kg, respectively. The overall decrease in acute toxicity compared to that for free drug amounted to 50-fold. At a dose of 30-80 mg/kg the loposomal diamidine was satisfactorily tolerated by sheep and horses, while free diamidine is lethal to these animals at 10mg/kg. The liposome-encapsulated diamidine had no effect on metabolic functions of the liver. After four i.m. injections of the liposomal diamidine at a dose of 30 mg/kg we observed a 10% increase in haemoglobin content and an elevation in erythrocyte count in the blood of Babesia equi-infected horses. This indicates a therapeutic effect of the liposomal form of the drug. C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02114. NR 0 TC 8 Z9 8 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-2048 J9 J MICROENCAPSUL JI J. Microencapsul. PD NOV-DEC PY 1994 VL 11 IS 6 BP 627 EP 632 DI 10.3109/02652049409051112 PG 6 WC Chemistry, Applied; Engineering, Chemical; Pharmacology & Pharmacy SC Chemistry; Engineering; Pharmacology & Pharmacy GA PU424 UT WOS:A1994PU42400003 PM 7884627 ER PT J AU WULLNER, U YOUNG, AB PENNEY, JB BEAL, MF AF WULLNER, U YOUNG, AB PENNEY, JB BEAL, MF TI 3-NITROPROPIONIC ACID TOXICITY IN THE STRIATUM SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 3-NITROPROPIONIC ACID; STRIATUM; STRIOSOMES; ENKEPHALIN; SUBSTANCE P; HUNTINGTONS DISEASE ID D-ASPARTATE RECEPTOR; HUNTINGTONS-DISEASE; BASAL GANGLIA; BINDING-SITES; SUBSTANCE-P; RAT-BRAIN; NEURONS; ACETYLCHOLINESTERASE; GLUTAMATE; SEQUENCE AB We examined the effects of chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) in doses ranging from 12 to 16 mg/kg/day for 30 days on striatal cytoarchitecture in rats. Administration of 3-NP at a dose of 16 mg/kg/day resulted in large lesions with a central necrotic core that was depleted of both neurons and glia. Glial fibrillary acidic protein (GFAP) gene expression was decreased in the lesion core, whereas the tissue surrounding this area showed a massive increase in signal intensity. Enkephalin and substance P mRNA expression in the striatum showed dose-dependent decreases following administration of 3-NP. A substantial decrease occurred even in animals treated with 3-NP at a dose of 12 mg/kg/day, in which there was little discernible neuronal loss and no increase in GFAP gene expression. In contrast to the decrease in enkephalin and substance P mRNA expression, somatostatin mRNA-expressing neurons were largely preserved. There was no preferential loss of [H-3]naloxone patches in the rat striatum following chronic administration of 3-NP. in animals treated with 12-15 mg/kg/day neither the area nor binding density of the patches was changed. To study the effect of 3-NP on N-methyl-D-aspartate (NMDA)gated Ca2+ channels we used in vivo administration of [H-3]MK-801. Three hours after a single injection of 3-NP at a dose of 30 mg/kg there was a three- to fivefold increase in [H-3]MK-801 binding in cortex and striatum as compared with saline-treated animals, consistent with an activation of NMDA receptors. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NINDS NIH HHS [NS16367, NS10828, NS19613] NR 39 TC 109 Z9 109 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1994 VL 63 IS 5 BP 1772 EP 1781 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PN458 UT WOS:A1994PN45800023 PM 7523600 ER PT J AU LEUCHTER, AF DUNKIN, JJ LUFKIN, RB ANZAI, Y COOK, IA NEWTON, TF AF LEUCHTER, AF DUNKIN, JJ LUFKIN, RB ANZAI, Y COOK, IA NEWTON, TF TI EFFECT OF WHITE-MATTER DISEASE ON FUNCTIONAL CONNECTIONS IN THE AGING BRAIN SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID SOMATOSENSORY EVOKED-POTENTIALS; HEALTHY ELDERLY SUBJECTS; MAGNETIC-RESONANCE; ALZHEIMERS-DISEASE; LEUKO-ARAIOSIS; EEG COHERENCE; PERIVENTRICULAR HYPERINTENSITY; DIFFERENTIAL-DIAGNOSIS; MULTIINFARCT DEMENTIA; SENILE DEMENTIA AB Periventricular white matter hyperintensities (PVHs) seen on T2 weighted MRI studies are common in elderly people and often represent demyelination of fibres. Damage to these fibres could lead to functional disconnection between brain regions. Electroencephalographic coherence, a measure of shared electrical activity between regions, was examined to determine if there was evidence for such disconnection. Twenty two subjects with clinically diagnosed dementia of the Alzheimer's type, 16 with multi-infarct dementia, and 18 normal controls were studied. It was hypothesised that coherence between areas presumably linked by fibres that traverse the periventricular region would be decreased in subjects with PVHs, and that PVHs would have a stronger association with decreased coherence than clinical diagnosis. It was also hypothesised that coherence between areas presumably connected by long corticocortical tracts that are neuroanatomically separated from the ventricles would be low in patients with Alzheimer's disease because of pyramidal cell death in this group, but would not be affected by the presence of PVHs. Patients with PVHs in fact had lower coherence than those without PVHs in the pre-Rolandic and post-Rolandic areas, where connecting fibres traverse the periventricular region. There was no effect of PVHs, however, on coherence between areas separated by the Rolandic fissure that were connected by long corticocortical tracts; this coherence was lowest among the patients with Alzheimer's disease. These patterns of association suggest that coherence may detect different types of neurophysiological ''disconnection,'' and may be sensitive to selective damage to different fibre pathways. C1 UNIV CALIF LOS ANGELES,NEUROPSYCHIAT INST & HOSP,DEPT PSYCHIAT,QEEG LAB,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,NEUROPSYCHIAT INST & HOSP,DEPT BIOBEHAV SCI,QEEG LAB,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DEPT PSYCHIAT,LOS ANGELES,CA 90073. OI newton, thomas/0000-0002-3198-5901 FU NIA NIH HHS [P30 AG10123]; NIMH NIH HHS [MH 40705] NR 63 TC 50 Z9 50 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 1994 VL 57 IS 11 BP 1347 EP 1354 DI 10.1136/jnnp.57.11.1347 PG 8 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA PQ919 UT WOS:A1994PQ91900009 PM 7964810 ER PT J AU GILLES, FH SOBEL, EL LEVITON, A TAVARE, CJ HEDLEYWHYTE, ET BLANK, WF FULLING, KH BLAIR, JD DEMELLO, D SOTREL, A ORSINI, EN ISAACS, H RORKE, LB HASHIDA, Y PRICE, RA YUNIS, EJ ZAIAS, BW BECKER, LE DAVIS, RL DELEON, GA HUFF, D MESTRE, G SHAMSZADEH, M ADELMAN, LS AVERILL, RD DEGIROLAMI, U KLEINMAN, GM MORRIS, JH RICHARDSON, EP SCHOENE, WC SMITH, TW SOBEL, RA KENNEY, C MORELLI, D SOBEL, E AF GILLES, FH SOBEL, EL LEVITON, A TAVARE, CJ HEDLEYWHYTE, ET BLANK, WF FULLING, KH BLAIR, JD DEMELLO, D SOTREL, A ORSINI, EN ISAACS, H RORKE, LB HASHIDA, Y PRICE, RA YUNIS, EJ ZAIAS, BW BECKER, LE DAVIS, RL DELEON, GA HUFF, D MESTRE, G SHAMSZADEH, M ADELMAN, LS AVERILL, RD DEGIROLAMI, U KLEINMAN, GM MORRIS, JH RICHARDSON, EP SCHOENE, WC SMITH, TW SOBEL, RA KENNEY, C MORELLI, D SOBEL, E TI HISTOLOGIC FEATURE RELIABILITY IN CHILDHOOD NEURAL TUMORS SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE BRAIN TUMOR; CHILDREN; HISTOLOGY; JACCARD; KAPPA; OBSERVER RELIABILITY ID CERVICAL INTRAEPITHELIAL NEOPLASIA; INTER-OBSERVER VARIATION; HISTOPATHOLOGICAL DIAGNOSIS; PSYCHIATRIC-DIAGNOSIS; CLINICAL-SIGNIFICANCE; GRADING SYSTEMS; REPRODUCIBILITY; KAPPA; CLASSIFICATION; INTEROBSERVER AB We studied intraobserver reproducibility in recognizing the presence or absence of 57 histologic features or patterns in a random subset of tumors (822) from the Childhood Brain Tumor Consortium database. The study protocol maximized consistency of the observer. We found that only six histologic features had high (greater than or equal to 0.75) reliability estimates while a large number had intermediate estimates of 0.50-0.74. Supratentorial or infratentorial tumor location sometimes altered reliability. Reliability estimates were unacceptable for certain histologic features often used as diagnostic criteria, descriptors of tumor characteristics, or markers of anaplasia. We hypothesize that low reliability reflects, in part, the need for more specific operational definitions, particularly those with subjective boundaries (e.g. the cellular density constituting the histologic boundary between high and intermediate cell density). Rarity of a feature in the microscopic section (e.g. granular bodies) may also contribute to low reliability. We also show that the kappa statistic, a commonly used measure of reliability, is inappropriate for very common or uncommon histologic features (e.g. features at the extremes of prevalence in the study cases) and we offer a simple empiric method for determining when an alternative measure, the Jaccard statistic, is appropriate. C1 CHILDRENS HOSP LOS ANGELES,MED LAB,LOS ANGELES,CA. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. UNIV SO CALIF,SCH MED,DEPT PREVENT MED,LOS ANGELES,CA 90033. CHILDRENS HOSP,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. BARNES & ST LOUIS CHILDRENS HOSP,ST LOUIS,MO. CARDINAL GLENNON MEM HOSP CHILDREN,ST LOUIS,MO. CHILDRENS HOSP,DENVER,CO. CHILDRENS HOSP PHILADELPHIA,PHILADELPHIA,PA. CHILDRENS HOSP PITTSBURGH,PITTSBURGH,PA. HOSP SICK CHILDREN,TORONTO,ON,CANADA. UNIV SO CALIF,MED CTR,LOS ANGELES,CA. TUFTS UNIV,SCH MED,MEDFORD,MA 02155. UNIV MICHIGAN,SCH MED,ANN ARBOR,MI 48109. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. UNIV MASSACHUSETTS,SCH MED,AMHERST,MA 01003. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CONNECTICUT,YALE MED SCH,STORRS,CT 06269. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. RP GILLES, FH (reprint author), CHILDRENS HOSP LOS ANGELES,DEPT PATHOL,4650 SUNSET BLVD,LOS ANGELES,CA 90027, USA. FU NCI NIH HHS [R01 CA20462, R01 CA49532] NR 63 TC 26 Z9 26 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 1994 VL 53 IS 6 BP 559 EP 571 PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA PP520 UT WOS:A1994PP52000002 PM 7964897 ER PT J AU FOLLI, F BONFANTI, L RENARD, E KAHN, CR MERIGHI, A AF FOLLI, F BONFANTI, L RENARD, E KAHN, CR MERIGHI, A TI INSULIN-RECEPTOR SUBSTRATE-1 (IRS-1) DISTRIBUTION IN THE RAT CENTRAL-NERVOUS-SYSTEM SO JOURNAL OF NEUROSCIENCE LA English DT Article DE INSULIN RECEPTOR SUBSTRATE 1; INSULIN-LIKE GROWTH FACTOR 1; INSULIN RECEPTOR KINASE; INSULIN-LIKE GROWTH FACTOR I RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; CNS; IMMUNOCYTOCHEMISTRY ID GROWTH FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; TYROSINE KINASE; AUTORADIOGRAPHIC LOCALIZATION; SIGNAL TRANSDUCTION; PROTEIN-KINASES; BINDING-SITES; ANIMAL-MODELS; INTACT RAT; IGF-I AB Insulin receptor substrate 1 (IRS-1) is the primary cytosolic substrate of the insulin and insulin-like growth factor-I (IGF-I) receptors. Following tyrosine phosphorylation IRS-I binds to and activates specific proteins containing SH2 domains. Using biochemical and immunocytochemical techniques, we have mapped the distribution of IRS-1 in the CNS of the adult rat and compared it with that of insulin and IGF-I receptors and phosphatidylinositol 3-kinase (PI-3 kinase), a signaling molecule functionally related to IRS-1. Immunoprecipitation and Western blotting experiments demonstrate the presence of substantial amounts of IRS-1, insulin receptor, and PI-3 kinase in the brain. IRS-1 immunoreactivity is widely distributed in neurons from several areas of the brain and spinal cord. The cerebral cortex, the hippocampus, many hypothalamic and thalamic nuclei, the basal ganglia, the cerebellar cortex, the brainstem nuclei, and the lamina X of the spinal cord are particularly rich of immunopositive nerve cells. In these areas most of the neurons immunoreactive for IRS-1 are also stained by either anti-insulin receptor or anti-IGF-I receptor antibodies as well as PI-3 kinase antiserum. IRS-1 immunostaining was very weak or totally absent in neurons of the olfactory bulb, the supraoptic and paraventricular nuclei, the mesencephalic trigeminal nucleus, and the granule cell layer of the cerebellum, despite the fact that these areas were immunolabeled with antibodies against insulin or IGF-I receptors and/or PI-3 kinase. These results show that neurons in the adult rat CNS are endowed with some of the components of the early signaling pathway for growth factors of the insulin/IGF-I family, although IRS-1 has a distribution distinct from that of the two receptors. C1 UNIV TURIN, DIPARTIMENTO MORFOFISIOL, I-10126 TURIN, ITALY. BRIGHAM & WOMENS HOSP, DEPT MED, JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02215 USA. OI folli, franco/0000-0001-9824-5222; Merighi, Adalberto/0000-0002-1140-3556 FU NIDDK NIH HHS [DK 31036, DK 33201] NR 70 TC 105 Z9 106 U1 0 U2 2 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 NOV PY 1994 VL 14 IS 11 BP 6412 EP 6422 PN 1 PG 11 WC Neurosciences SC Neurosciences & Neurology GA PQ381 UT WOS:A1994PQ38100010 PM 7965046 ER PT J AU BOGDANOV, AA CALLAHAN, RJ WILKINSON, RA MARTIN, C CAMERON, JA FISCHMAN, AJ BRADY, TJ WEISSLEDER, R AF BOGDANOV, AA CALLAHAN, RJ WILKINSON, RA MARTIN, C CAMERON, JA FISCHMAN, AJ BRADY, TJ WEISSLEDER, R TI SYNTHETIC COPOLYMER KIT FOR RADIONUCLIDE BLOOD-POOL IMAGING SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE POLYETHYLENE GLYCOL; POLY-L-LYSINE; BLOOD POOL; IMAGING; KIT ID HUMAN-SERUM-ALBUMIN; SCINTIGRAPHIC DIAGNOSIS; CONTRAST AGENT; INVIVO; TECHNETIUM-99M; PROTEINS; CELLS; VENTRICULOGRAPHY; LIPOSOMES AB A synthetic blood pool imaging agent labeled with Tc-99m is reported. Methods: The agent, methoxypolyethylene glycolpoly-L-lysyl-diethylenetriaminepentaacetate monoamide was synthesized from a covalent graft copolymer of methoxypolyethylene glycol succinate (molecular weight 5.1 kD) and poly-L-lysine (molecular weight average 35.6 kD) with subsequent modification of the product with diethytenetriamineacetyl residues. The polymer was formulated into a kit that contained Sn(II) and sodium acetate for radiolabeling with (99mTc). Biodistribution studies were performed in rats. Blood-pool imaging and blood clearance determination was carried out in rabbits and in a rhesus monkey. Results: The Tc-99m-labeled agent [specific activity greater than 3.7 GBqimg; radiochemical purity more than 98% by thin-layer and high-performance liquid chromatography (HPLC)] demonstrated remarkable stability in solution (pH 5.5-6.5) with no radioactive products of degradation detectable by HPLC even at 24 hr postlabeling. The agent exhibited prolonged circulation in the blood with a half-life of 31.5 hr in rabbits. Biodistribution in rats showed a lack of substantial accumulation of the agent in the reticuloendothelial system. Sequential acquisitions were performed in a rhesus monkey. The Tc-99m-labeled polymer kit was compared with the Tc-99m-red blood cells (RBCs) labeled in vitro. Both methods produced similar heart-to-lung ratios. The ratios remained essentially unchanged for up to 15 hr postinjection. Conclusion: The Tc-99m-labeled methoxypolyethylene glycol-poly-L-lysyl-diethylenetriamine pentaacetate monoamide is an attractive alternative to radiolabeled RBCs for blood pool imaging applications. C1 MASSACHUSETTS GEN HOSP EAST,DIV NUCL MED,BOSTON,MA 02129. RP BOGDANOV, AA (reprint author), MASSACHUSETTS GEN HOSP EAST,NMR CTR,DEPT RADIOL,ROOM 5416,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 33 TC 21 Z9 21 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 1994 VL 35 IS 11 BP 1880 EP 1886 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PT868 UT WOS:A1994PT86800032 PM 7965173 ER PT J AU MACBURNEY, M YOUNG, LS ZIEGLER, TR WILMORE, DW AF MACBURNEY, M YOUNG, LS ZIEGLER, TR WILMORE, DW TI A COST-EVALUATION OF GLUTAMINE-SUPPLEMENTED PARENTERAL-NUTRITION IN ADULT BONE-MARROW TRANSPLANT PATIENTS SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID INTESTINAL-MUCOSA; DOUBLE-BLIND; SUPPORT AB Objective In a randomized, double-blind, prospective clinical trial, we evaluated the metabolic effects of glutamine-supplemented parenteral nutrition in patients with bone marrow transplants. We compared hospital charge and cost data for the two groups of patients in the trial. Design Retrospective review. Setting Bone Marrow Transplant Unit, Brigham and Women's Hospital, Boston, Mass. Subjects Forty-three patients admitted to the Bone Marrow Transplant Unit were assigned randomly to receive either standard parenteral nutrition or an isocaloric, isonitrogenous parenteral nutrition solution containing glutamine starting on day 1 after bone marrow transplant. The two groups were well matched for diagnosis, antineoplastic treatment, and sex. Measures The primary clinical end points evaluated were nitrogen balance, length of hospitalization, incidence of infection, and results of microbial culture. After completion of the study, we compared the hospital charges for the categories of room and board, surgery, laboratory, pharmacy, radiology, ancillary, and miscellaneous between the two groups of patients. Statistical analysis performed The two groups were compared using the unpaired t test or Mann-Whitney test for nonparametric measurements. AP value of <.05 was consid ered significant. Results Nitrogen balance improved in the glutamine-supplemented group compared with control subjects (-1.4 +/- 0.5 g/day vs 4.2 +/- 1.2 g/day, respectively; P=.002). Length of hospitalization was significantly shorter in the glutamine-supplemented group than in the control group (29 +/- 1 day vs 36 +/- 2 days, respectively; P=.017). The incidence of positive microbial cultures and clinical infection was also significantly lower with glutamine supplementation. Hospital charges were $21,095 per patient less in the glutamine-supplemented group compared with charges for patients who received standard therapy. Room and board charges were significantly different: $51,484 +/- 2,647 for the glutamine-supplemented group vs $61,591 +/- 3,588 in the control group (P=.02). Conclusion This intervention study using a new therapy demonstrated clinical and nutritional benefits to patients and cost savings to the hospital. C1 BRIGHAM & WOMENS HOSP,SURG METAB & NUTR LABS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA. RP MACBURNEY, M (reprint author), BRIGHAM & WOMENS HOSP,NUTR SUPPORT SERV,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 14 TC 55 Z9 55 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 NOV PY 1994 VL 94 IS 11 BP 1263 EP 1266 DI 10.1016/0002-8223(94)92457-0 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PQ974 UT WOS:A1994PQ97400012 PM 7963169 ER PT J AU YOSHIKAWA, TT AF YOSHIKAWA, TT TI A TRIBUTE TO SOLOMON,DAVID,H., MD SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter RP YOSHIKAWA, TT (reprint author), US DEPT VET AFFAIRS,WASHINGTON,DC 20422, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 1994 VL 42 IS 11 BP 1219 EP 1219 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PQ005 UT WOS:A1994PQ00500019 PM 7963216 ER PT J AU MCCORMICK, KA LANG, N ZIEISTORFF, R MILHOLLAND, K SABA, V JACOX, A AF MCCORMICK, KA LANG, N ZIEISTORFF, R MILHOLLAND, K SABA, V JACOX, A TI TOWARD STANDARD CLASSIFICATION SCHEMES FOR NURSING LANGUAGE - RECOMMENDATIONS OF THE AMERICAN-NURSES-ASSOCIATION STEERING-COMMITTEE-ON-DATABASES-TO-SUPPORT-CLINICAL-NURSING-PRACTICE SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB The American Nurses Association (ANA) Cabinet on Nursing Practice mandated the formation of the Steering Committee on Databases to Support Clinical Nursing Practice. The Committee has established the process and the criteria by which to review and recommend nursing classification schemes based on the ANA Nursing Process Standards and elements contained in the Nursing Minimum Data Set (NMDS) for inclusion of nursing data elements in national databases. Four classification schemes have been recognized by the Committee for use in national databases. These classification schemes have been forwarded to the National Library of Medicine (NLM) for inclusion in the Unified Medical Language System (UMLS) and to the International Council of Nurses for the development of a proposed International Classification of Nursing Practice. C1 AGCY HLTH CARE POLICY & RES,ROCKVILLE,MD. UNIV PENN,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GEORGETOWN UNIV,WASHINGTON,DC. JOHNS HOPKINS UNIV,BALTIMORE,MD. RP MCCORMICK, KA (reprint author), AMER NURSES ASSOC INC,600 MARYLAND AVE,SW,SUITE 100 W,WASHINGTON,DC 20024, USA. NR 34 TC 44 Z9 45 U1 0 U2 1 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 NOV-DEC PY 1994 VL 1 IS 6 BP 421 EP 427 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 QE642 UT WOS:A1994QE64200001 PM 7850567 ER PT J AU THIER, SO AF THIER, SO TI THE SOCIAL AND SCIENTIFIC VALUE OF BIOMEDICAL-RESEARCH SO JOURNAL OF THE ROYAL COLLEGE OF PHYSICIANS OF LONDON LA English DT Article RP THIER, SO (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 5 Z9 5 U1 0 U2 4 PU ROY COLL PHYS LONDON EDITORIAL OFFICE PI LONDON PA 11 ST ANDREWS PLACE REGENTS PARK, LONDON, ENGLAND NW1 4LE SN 0035-8819 J9 J ROY COLL PHYS LOND JI J. R. Coll. Physicians Lond. PD NOV-DEC PY 1994 VL 28 IS 6 BP 541 EP 543 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA PW903 UT WOS:A1994PW90300020 PM 7884712 ER PT J AU WILLIAMS, RD DAMBRA, MN MAIONE, TE LYNCH, KE KEENE, DF AF WILLIAMS, RD DAMBRA, MN MAIONE, TE LYNCH, KE KEENE, DF TI RECOMBINANT PLATELET FACTOR-4 REVERSAL OF HEPARIN IN HUMAN CARDIOPULMONARY BYPASS BLOOD SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID CATASTROPHIC PULMONARY VASOCONSTRICTION; HUMAN MEGAKARYOCYTOPOIESIS INVITRO; FACTOR-IV; COMPLEMENT ACTIVATION; PROTAMINE SULFATE; ADVERSE REACTIONS; ANTICOAGULATION; NEUTRALIZATION; COMPLEXES; RELEASE AB The ability of recombinant platelet factor 4, a protein of human origin with high heparin affinity, and the present clinical heparin reversal agent, protamine, to neutralize heparin in human whole blood was studied by means of three standard whole blood coagulation tests: whole blood clotting time, heparin assay, and activated clotting time. Ten subjects were chosen at random among patients undergoing cardiopulmonary bypass operations. Heparinized blood, free of protamine, was obtained from the bypass reservoir for testing. Whole blood aliquots, without reversal agents (controls) or with either protamine (10, 20, 30, or 40 mu g/ml) or recombinant platelet factor 4 (10, 20, 40, or 80 mu g/ml), were analyzed. The quantity of each agent required to reverse the ten samples, using 95 % upper confidence bounds (t distribution) was determined for each method. Recombinant platelet factor 4 reversed heparin at 40 mu g/ml and protamine at 20 mu g/ml, suggesting a reversal ratio for recombinant platelet factor 4/protamine of 2:1 on a milligram basis. Further, currently available methods for testing coagulation should be reliable, without modification, to monitor the restoration of normal coagulation parameters with recombinant platelet factor 4 after cardiopulmonary bypass. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC ANESTHESIA GRP,BOSTON,MA 02114. REPLIGEN CORP,CAMBRIDGE,MA 02139. NR 54 TC 10 Z9 10 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD NOV PY 1994 VL 108 IS 5 BP 975 EP 983 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PQ516 UT WOS:A1994PQ51600023 PM 7967683 ER PT J AU BROMLEY, B BENACERRAF, BR AF BROMLEY, B BENACERRAF, BR TI SOLID MASSES ON THE FETAL SURFACE OF THE PLACENTA - DIFFERENTIAL-DIAGNOSIS AND CLINICAL OUTCOME SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID CHORIOANGIOMA AB We identified 10 cases of solid masses on the fetal surface of the placenta prospectively that were thought to represent chorioangiomas. Pathologic assessment of the placenta revealed five chorioangiomas and five placental hemorrhages. The five chorioangiomas ranged in size from 4 to 10 cm and four of these five fetuses were delivered uneventfully at term. Only one fetus showed evidence of cardiac decompensation and did not survive. Three of the five women with placental bleeds delivered their infants between 33 and 34 weeks' gestation, but all five infants did well. This series shows that the sonographic appearance of chorioangioma was indistinguishable from placental hemorrhage, and even large chorioangiomas may be associated with good neonatal outcome. C1 HARVARD UNIV,SCH MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA. NR 9 TC 24 Z9 26 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 NOV PY 1994 VL 13 IS 11 BP 883 EP 886 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA PQ660 UT WOS:A1994PQ66000010 PM 7837336 ER PT J AU MCDOUGAL, WS AF MCDOUGAL, WS TI VERRUCOUS CARCINOMA OF THE PENIS - RETROSPECTIVE ANALYSIS OF 32 CASES - COMMENT SO JOURNAL OF UROLOGY LA English DT Article RP MCDOUGAL, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT UROL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1478 EP 1479 PN 1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PL685 UT WOS:A1994PL68500035 ER PT J AU ZIETMAN, AL SHIPLEY, WU AF ZIETMAN, AL SHIPLEY, WU TI THE VALUE OF SERIAL PROSTATE-SPECIFIC ANTIGEN DETERMINATIONS 5 YEARS AFTER RADIOTHERAPY - STEEPLY INCREASING VALUES CHARACTERIZE 80-PERCENT OF PATIENTS SO JOURNAL OF UROLOGY LA English DT Letter ID RADICAL PROSTATECTOMY; CARCINOMA; CANCER RP ZIETMAN, AL (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 9 TC 4 Z9 4 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 NOV PY 1994 VL 152 IS 5 BP 1564 EP 1565 PN 1 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PL685 UT WOS:A1994PL68500066 PM 7523713 ER PT J AU HANKS, GE PEARSON, JD CATALONA, WJ LINEHAN, WM BAGSHAW, MA TRIBUKAIT, B LANGE, PH ADOLFSSON, J PAULSON, DF AF HANKS, GE PEARSON, JD CATALONA, WJ LINEHAN, WM BAGSHAW, MA TRIBUKAIT, B LANGE, PH ADOLFSSON, J PAULSON, DF TI DISCUSSION SO JOURNAL OF UROLOGY LA English DT Discussion C1 AMER COLL RADIOL,PHILADELPHIA,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA. NIA,CTR GERONTOL RES,LONGITUDINAL STUDIES BRANCH,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD. JOHNS HOPKINS UNIV HOSP,JAMES BUCHANAN BRADY UROL INST,BALTIMORE,MD 21205. WASHINGTON UNIV,SCH MED,DIV UROL SURG,ST LOUIS,MO. STANFORD UNIV,SCH MED,DEPT RADIAT ONCOL,STANFORD,CA. UNIV WASHINGTON,SCH MED,DEPT UROL,SEATTLE,WA. KAROLINSKA HOSP,DEPT UROL,STOCKHOLM,SWEDEN. KAROLINSKA HOSP,DEPT PATHOL,CYTOL SECT,STOCKHOLM,SWEDEN. LINKOPING UNIV,DEPT HLTH & SOC,LINKOPING,SWEDEN. DUKE UNIV,MED CTR,DIV UROL SURG,DURHAM,NC. RP HANKS, GE (reprint author), FOX CHASE CANC CTR,DEPT RADIAT ONCOL,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. 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 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1749 EP 1750 PN 2 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600020 ER PT J AU SHIPLEY, WU AF SHIPLEY, WU TI RADICAL TREATMENT WITH RADIATION OF EARLY-STAGE PROSTATE-CANCER - IMPRESSIVE RESULTS WITH LONG-TERM FOLLOW-UP SO JOURNAL OF UROLOGY LA English DT Editorial Material RP SHIPLEY, WU (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,GENITOURINARY ONCOL UNIT,BOSTON,MA, USA. NR 1 TC 5 Z9 5 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 NOV PY 1994 VL 152 IS 5 BP 1773 EP 1774 PN 2 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600027 PM 7933236 ER PT J AU HANKS, GE HANLON, A SCHULTHEISS, T CORN, B SHIPLEY, WU LEE, WR AF HANKS, GE HANLON, A SCHULTHEISS, T CORN, B SHIPLEY, WU LEE, WR TI EARLY PROSTATE-CANCER - THE NATIONAL RESULTS OF RADIATION TREATMENT FROM THE PATTERNS OF CARE AND RADIATION-THERAPY ONCOLOGY GROUP STUDIES WITH PROSPECTS FOR IMPROVEMENT WITH CONFORMAL RADIATION AND ADJUVANT ANDROGEN DEPRIVATION SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT Conference on Detection and Treatment of Early Stage Prostate Cancer CY DEC 03-05, 1993 CL CRYSTAL CITY, VA SP AMER UROL ASSOC, AMER CANC SOC, NCI, AMER COLL SURGEONS COMMISS CANC DE PROSTATIC NEOPLASMS; RADIOTHERAPY; ANDROGENS; DELIVERY OF HEALTH CARE ID EXTERNAL BEAM IRRADIATION; RADICAL PROSTATECTOMY; CARCINOMA; ADENOCARCINOMA; RTOG-77-06; ANTIGEN; RTOG AB Long-term outcome of the Patterns of Care Study and the Radiation Therapy Oncology Group are used to demonstrate the national average results of treating early prostate cancer in the United States. A group of patients with stage T1B2 disease and pathologically negative lymph nodes showed excellent 10-year survival rates and freedom from clinical evidence of disease, while prostate specific antigen (PSA) correlations in 10-year survivors indicate that 88% were clinically free of cancer and had a PSA level of less than 4.0 mg./nl., and 65% had a PSA level of less than 1.5 ng./ml. The latter group represented clinical and biochemical cures. The improvement noted in outcome of locally advanced prostate cancer treatment by Radiation Therapy Oncology Group prospective trials combining androgen deprivation and radiation therapy is presented. These trials will be extended to the poor prognosis group with stage T1,2 disease. The advantages of conformal therapy in acute and late morbidity are illustrated with preliminary evidence of improved PSA response as a result of improved technique and higher dose associated with conformal 3-dimensional treatment. C1 AMER COLL RADIOL,PHILADELPHIA,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP HANKS, GE (reprint author), FOX CHASE CANC CTR,DEPT RADIAT ONCOL,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. OI Schultheiss, Timothy/0000-0002-8984-196X FU NCI NIH HHS [CA21661, CA60264-01, CM-87275-03] NR 28 TC 52 Z9 52 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 NOV PY 1994 VL 152 IS 5 BP 1775 EP 1780 PN 2 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600028 PM 7523724 ER PT J AU SHIPLEY, WU ZIETMAN, AL HANKS, GE COEN, JJ CAPLAN, RJ WON, M ZAGARS, GK ASBELL, SO AF SHIPLEY, WU ZIETMAN, AL HANKS, GE COEN, JJ CAPLAN, RJ WON, M ZAGARS, GK ASBELL, SO TI TREATMENT RELATED SEQUELAE FOLLOWING EXTERNAL-BEAM RADIATION FOR PROSTATE-CANCER - A REVIEW WITH AN UPDATE IN PATIENTS WITH STAGES T1 AND T2 TUMOR SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT Conference on Detection and Treatment of Early Stage Prostate Cancer CY DEC 03-05, 1993 CL CRYSTAL CITY, VA SP AMER UROL ASSOC, AMER CANC SOC, NCI, AMER COLL SURGEONS COMMISS CANC DE PROSTATIC NEOPLASMS; RADIOTHERAPY; TREATMENT OUTCOME ID THERAPY; CARCINOMA; COMPLICATIONS; RADIOTHERAPY; IRRADIATION; MORBIDITY; TOXICITY AB The primary goal of radical radiation therapy in men with localized prostate carcinoma is cure and a secondary but important goal is to achieve cure without treatment related sequelae, such as loss of continence, rectal injury, loss of potency and the need for castration. A literature review of 2,611 men undergoing irradiation for all stages of localized prostatic carcinoma documented a 0.2% incidence of treatment related mortality, 1.9% severe complications, 0.9% incontinence and 33 to 60% maintenance of full potency 5 or more years after treatment. A separate analysis was made of 331 patients with only early tumors (stages T1 and T2) treated with conventional external beam radiation therapy to doses of 63 to 74 Gy. from 2 individual centers (Massachusetts General Hospital and M. D. Anderson Hospital) and 1 multi-institutional group (Radiation Therapy Oncology Group). Median followup was 6.1 years; however, in 2 series followup ranged to 14 years. This analysis revealed frequencies of treatment associated sequelae of 0% for mortality, 0% severe complications, 0.4% urinary incontinence, 5.4% genitourinary strictures (1.2% persisting), 5.1% hematuria (0.9% persisting) and 5.4% rectal bleeding (0.6% persisting). This composite analysis of men undergoing irradiation for stages T1 and T2 tumors with conventional fractionation and doses indicates that acute morbidity is minor and usually transient, severe injury is rare, most late gastrointestinal and genitourinary symptoms of radiation injury are neither permanent nor debilitating, and few symptoms of radiation injury develop beyond 5 years from treatment. These data, combined with the low progression rates (using prostate specific antigen criteria) following irradiation of men with early tumors, further substantiate the primary role of radical radiotherapy in the treatment of surgical risk adversive patients. C1 FOX CHASE CANC CTR,RADIAT THERAPY ONCOL GRP HEADQUARTERS,PHILADELPHIA,PA 19111. ALBERT EINSTEIN MED CTR,PHILADELPHIA,PA. MD ANDERSON HOSP,HOUSTON,TX. RP SHIPLEY, WU (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 24 TC 100 Z9 103 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1799 EP 1805 PN 2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600032 PM 7933239 ER PT J AU ZIETMAN, AL SHIPLEY, WU COEN, JJ AF ZIETMAN, AL SHIPLEY, WU COEN, JJ TI RADICAL PROSTATECTOMY AND RADICAL RADIATION-THERAPY FOR CLINICAL STAGE-T1 TO STAGE-T2 ADENOCARCINOMA OF THE PROSTATE - NEW INSIGHTS INTO OUTCOME FROM REPEAT BIOPSY AND PROSTATE-SPECIFIC ANTIGEN FOLLOW-UP SO JOURNAL OF UROLOGY LA English DT Article DE PROSTATIC NEOPLASMS; RADIOTHERAPY; PROSTATECTOMY; ANTIGENS, NEOPLASM ID PREDICT PATHOLOGICAL STAGE; EXTERNAL-BEAM RADIOTHERAPY; TRANS-RECTAL ULTRASOUND; CAPSULAR PENETRATION; GLEASON SCORE; SERUM PSA; CANCER; CARCINOMA; SURGERY; MEN AB Assessment of outcome following radical treatment for stages T1 to T2 prostate cancer has become more sensitive and rapid with the use of serum prostate specific antigen (PSA) in routine followup. PSA has identified substantially more failure following all radical therapies than was previously detected in series using clinical end points. Furthermore, it has also allowed a better assessment of the biological potential of histologically evident residual disease, that is a positive surgical margin after prostatectomy or positive repeat biopsy 2 years after radiation. Both situations are associated with subsequent biochemical failure in the majority of patients. The stages T1 to T2 cancer group is extremely heterogeneous. In the few series with PSA followup that have evaluated long-term (greater than a decade) outcome for this group some report cure rates well below 40% for surgery and radiation. When comparing the results of any radical treatment series (surgery versus surgery and radiation versus radiation, as well as radiation versus surgery) selection may have a crucial role in predicting outcome. Surgical series tend to contain more patients with stages T1 to T2a tumors of low grade who have low initial PSA values and are known to have negative nodes. These patients, when treated with radical radiation, also have a favorable prognosis. It is hoped that the introduction of screening programs will improve outcome through earlier disease detection. C1 BOSTON UNIV, MED CTR, DEPT RADIAT ONCOL, BOSTON, MA USA. RP ZIETMAN, AL (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT RADIAT ONCOL, GENITOURINARY ONCOL UNIT, BOSTON, MA 02114 USA. NR 46 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1806 EP 1812 PN 2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600033 PM 7523726 ER PT J AU MCCULLOUGH, DL BAGSHAW, MA SMITH, JA HANKS, GE WILT, TJ ZAGARS, GK FUKS, Z ZIPPE, C GRAYHACK, JT PAULSON, DF OESTERLING, JE HOWE, RJ ZIETMAN, AL RAMSEY, E SHIPLEY, WU DEKERNION, JB AF MCCULLOUGH, DL BAGSHAW, MA SMITH, JA HANKS, GE WILT, TJ ZAGARS, GK FUKS, Z ZIPPE, C GRAYHACK, JT PAULSON, DF OESTERLING, JE HOWE, RJ ZIETMAN, AL RAMSEY, E SHIPLEY, WU DEKERNION, JB TI DISCUSSION SO JOURNAL OF UROLOGY LA English DT Discussion C1 STANFORD UNIV,SCH MED,DEPT RADIAT ONCOL,STANFORD,CA 94305. FOX CHASE CANC CTR,DEPT RADIAT ONCOL,PHILADELPHIA,PA 19111. AMER COLL RADIOL,PHILADELPHIA,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. VET ADM MED CTR,DEPT MED,GEN INTERNAL MED SECT,MINNEAPOLIS,MN. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. VET ADM MED CTR,DEPT UROL,SEATTLE,WA 98108. UNIV WASHINGTON,SEATTLE,WA 98195. NR 2 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1813 EP 1815 PN 2 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600034 ER PT J AU WALSH, PC WASSON, J SCARDINO, PT MENON, M BARRY, MJ CARROLL, PR BECK, JR CATALONA, WJ WILT, TJ CHODAK, GW ZINCKE, H SIMPSON, KN AF WALSH, PC WASSON, J SCARDINO, PT MENON, M BARRY, MJ CARROLL, PR BECK, JR CATALONA, WJ WILT, TJ CHODAK, GW ZINCKE, H SIMPSON, KN TI DISCUSSION SO JOURNAL OF UROLOGY LA English DT Discussion ID PROSTATE-CANCER; TREATMENT STRATEGIES; SURVIVAL C1 JOHNS HOPKINS UNIV, SCH MED, DEPT UROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV HOSP, JAMES BUCHANAN BRADY UROL INST, BALTIMORE, MD 21205 USA. MATSUNAGA CONTE PROSTATE CANC RES CTR, SCOTT DEPT UROL, HOUSTON, TX USA. BAYLOR COLL MED, DEPT PATHOL, HOUSTON, TX 77030 USA. BAYLOR COLL MED, DEPT MED, HOUSTON, TX 77030 USA. METHODIST HOSP, HOUSTON, TX 77030 USA. STANFORD UNIV, MED CTR, DEPT UROL, STANFORD, CA 94305 USA. MASSACHUSETTS GEN HOSP, CTR EVALUAT, BOSTON, MA 02114 USA. BAYLOR COLL MED, DEPT PATHOL, INFORMAT TECHNOL PROGRAM, HOUSTON, TX 77030 USA. BAYLOR COLL MED, DEPT UROL, INFORMAT TECHNOL PROGRAM, HOUSTON, TX 77030 USA. KAMAN SCI CORP, COLORADO SPRINGS, CO USA. WASHINGTON UNIV, SCH MED, DIV UROL SURG, ST LOUIS, MO 63110 USA. VET ADM MED CTR, DEPT MED, GEN INTERNAL MED SECT, MINNEAPOLIS, MN USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. VET ADM MED CTR, DEPT UROL, SEATTLE, WA 98108 USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. UNIV CHICAGO, PRITZKER SCH MED, CHICAGO, IL 60637 USA. WEISS MEM HOSP, CTR PROSTATE & UROL, CHICAGO, IL USA. MAYO CLIN & MAYO FDN, DEPT UROL, ROCHESTER, MN 55905 USA. MAYO CLIN & MAYO FDN, BIOSTAT SECT, ROCHESTER, MN 55905 USA. RP WALSH, PC (reprint author), JOHNS HOPKINS UNIV, SCH MED, DEPT PATHOL, BALTIMORE, MD 21205 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1878 EP 1881 PN 2 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600050 ER PT J AU BARRY, MJ AF BARRY, MJ TI PROVING EARLY DETECTION AND TREATMENT OF PROSTATE-CANCER DOES MORE GOOD THAN HARM - THE NEED TO SUPPORT RANDOMIZED TRIALS ACTIVELY SO JOURNAL OF UROLOGY LA English DT Editorial Material ID TRENDS RP MASSACHUSETTS GEN HOSP, CTR MED PRACTICE EVALUAT, BOSTON, MA 02114 USA. NR 19 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1903 EP 1904 PN 2 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600055 PM 7933247 ER PT J AU CATALONA, WJ COCKETT, ATK GOHAGAN, JK WILT, TJ LANGE, PH CHODAK, GW OLSSON, CA MCCULLOUGH, DL PROROCK, PC BAGSHAW, MA SCARDINO, PT ANDRIOLE, GL RAMSEY, E KLEIN, EA BARRY, MJ MENON, M SMITH, AY CORREA, RJ SIMPSON, KN GRAYHACK, JT DEKERNION, JB KOONTZ, WW FEIGHTNER, JW HEMSTREET, GP AF CATALONA, WJ COCKETT, ATK GOHAGAN, JK WILT, TJ LANGE, PH CHODAK, GW OLSSON, CA MCCULLOUGH, DL PROROCK, PC BAGSHAW, MA SCARDINO, PT ANDRIOLE, GL RAMSEY, E KLEIN, EA BARRY, MJ MENON, M SMITH, AY CORREA, RJ SIMPSON, KN GRAYHACK, JT DEKERNION, JB KOONTZ, WW FEIGHTNER, JW HEMSTREET, GP TI DISCUSSION SO JOURNAL OF UROLOGY LA English DT Discussion ID LOCALIZED PROSTATE-CANCER C1 KAMAN SCI CORP, COLORADO SPRINGS, CO USA. NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. VET ADM MED CTR, DEPT MED, GEN INTERNAL MED SECT, MINNEAPOLIS, MN USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. VET ADM MED CTR, DEPT UROL, SEATTLE, WA 98108 USA. UNIV WASHINGTON, DEPT UROL, SEATTLE, WA 98195 USA. COLUMBIA UNIV, COLL PHYS & SURG,COLUMBIA PRESBYTERIAN MED CTR, SQUIER UROL CLIN,DEPT UROL, NEW YORK, NY USA. STANFORD UNIV, SCH MED, DEPT RADIAT ONCOL, STANFORD, CA 94305 USA. BAYLOR COLL MED, DEPT UROL, HOUSTON, TX 77030 USA. WASHINGTON UNIV, SCH MED, DIV UROL SURG, ST LOUIS, MO 63110 USA. WASHINGTON UNIV, SCH MED, DEPT LAB MED, ST LOUIS, MO 63110 USA. MASSACHUSETTS GEN HOSP, CTR MED PRACTICE EVALUAT, BOSTON, MA 02114 USA. UNIV N CAROLINA, SCH PUBL HLTH, DEPT HLTH POLICY & ADM, CHAPEL HILL, NC USA. UNIV CALIF LOS ANGELES, DEPT SURG, DIV UROL, LOS ANGELES, CA 90024 USA. MCMASTER UNIV, DEPT FAMILY MED, HAMILTON L8S 4L8, ON, CANADA. STANFORD UNIV, SCH MED, DEPT RADIAT ONCOL, STANFORD, CA 94305 USA. RP CATALONA, WJ (reprint author), WASHINGTON UNIV, SCH MED, DIV UROL SURG, 4960 CHILDRENS PL, ST LOUIS, MO 63110 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 EI 1527-3792 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1915 EP 1921 PN 2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600058 ER PT J AU MCCONELL, JD SHIPLEY, WU DISANTAGNESE, PA COCKETT, ATK CATALONA, WJ SCARDINO, PT HOWE, RJ LANGE, PH WASSON, JH WILT, TJ PEARSON, JD HOLTGREWE, HL OLSSON, CA AF MCCONELL, JD SHIPLEY, WU DISANTAGNESE, PA COCKETT, ATK CATALONA, WJ SCARDINO, PT HOWE, RJ LANGE, PH WASSON, JH WILT, TJ PEARSON, JD HOLTGREWE, HL OLSSON, CA TI DISCUSSION SO JOURNAL OF UROLOGY LA English DT Discussion C1 UNIV ROCHESTER,MED CTR,DEPT PATHOL & LAB MED,ROCHESTER,NY 14642. UNIV ROCHESTER,MED CTR,DEPT UROL,ROCHESTER,NY 14642. KAMAN SCI CORP,COLORADO SPRINGS,CO. WASHINGTON UNIV,SCH MED,DIV UROL SURG,ST LOUIS,MO 63110. BAYLOR COLL MED,DEPT UROL,HOUSTON,TX 77030. UNIV WASHINGTON,DEPT UROL,SEATTLE,WA 98195. VET ADM MED CTR,DEPT MED,GEN INTERNAL MED SECT,MINNEAPOLIS,MN. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. VET ADM MED CTR,DEPT UROL,SEATTLE,WA 98108. UNIV WASHINGTON,SEATTLE,WA 98195. COLUMBIA UNIV,COLL PHYS & SURG,COLUMBIA PRESBYTERIAN MED CTR,SQUIER UROL CLIN,DEPT UROL,NEW YORK,NY. RP MCCONELL, JD (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,GERITOURINARY ONCOL UNIT,BOSTON,MA, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1994 VL 152 IS 5 BP 1939 EP 1940 PN 2 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PL686 UT WOS:A1994PL68600063 ER PT J AU KLYACHKIN, ML DHARA, S LITALIEN, GJ ABBOTT, WM AF KLYACHKIN, ML DHARA, S LITALIEN, GJ ABBOTT, WM TI ARTERIAL GEOMETRIC ABNORMALITIES PRODUCE 2-DIMENSIONAL COMPLIANCE DISTURBANCES SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID WALL; HYPERPLASIA AB Purpose: This study describes the two-dimensional compliance changes that develop in low-grade hemodynamically insignificant stenoses. Methods: Twenty-four male Sprague-Dawley rats were used in the study. In 14 rats, balloon injury and endothelial denudation of the common carotid artery was followed by the application of a ligature, which produced a 20% narrowing of the outer diameter; five other rats were similarly injured without creating a stenosis, and five were stenosed without injury. The latter two groups served as control. Two-dimensional measures of arterial wall motions were obtained 30 minutes and 3 days after surgery by use of a video motion analyzer. Subsequently, circumferential (C-c) and longitudinal (C-l) compliance values were calculated and analyzed. Results: At 30 minutes, in the injured stenosed arteries, overall C-c was significantly greater than in the nonstenosed injured arteries at all measured points along the artery. Both stenosed injured and stenosed noninjured arteries also displayed increased C-c both proximal and distal to the stenoses compared with C-c values furthest from the stenosis. C-l values in the stenosed arteries, both injured and noninjured, became negative across the stenosis. All two-dimensional compliance changes occurred within the area of arterial narrowing and gradually resolved approaching the nonstenotic region of the artery. At systole, in the adjacent to the stenosis arterial segments, circumferential distension was accompanied by simultaneous longitudinal compression. Three days after surgery, although C-c increased proximal and distal to the stenosis and C-l decreased in the areas adjacent to the stenoses, no statistically significant difference was found. Conclusions: Low-grade stenosis results in a longitudinal compression accompanied by a relatively increased circumferential distension of arterial segments adjacent to the stenotic region. This pattern is not initiated or influenced by the presence or absence of endothelial cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,DIV VASC SURG,VASC RES LAB,BOSTON,MA 02114. NR 20 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 1994 VL 20 IS 5 BP 795 EP 802 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA PR672 UT WOS:A1994PR67200016 PM 7966815 ER PT J AU MOORE, JP WILLEY, RL LEWIS, GK ROBINSON, J SODROSKI, J AF MOORE, JP WILLEY, RL LEWIS, GK ROBINSON, J SODROSKI, J TI IMMUNOLOGICAL EVIDENCE FOR INTERACTIONS BETWEEN THE FIRST, 2ND, AND 5TH CONSERVED DOMAINS OF THE GP120 SURFACE GLYCOPROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; VARIABLE REGIONS; PROTEIN SEQUENCES; SOLUBLE CD4; BINDING; HIV-1; GENE; ASSOCIATION; EPITOPES AB We have used a combination of genetic and immunological techniques to explore how amino acid substitutions in the second conserved (C2) domain of gp120 from human immunodeficiency virus type 1 (HIV-1) affect the conformation of the protein. It was reported previously (R. L. Willey, E. M. Ross, A. J. Buckler-White, T. S. Theodore, and M. A. Martin. J. Virol. 63:3595-3600, 1989) that an asparagine-glutamine (N/Q) substitution at C2 residue 267 of HIV-1 NL4/3 reduced virus infectivity, but that infectivity was restored by a compensatory amino acid change (serine-glutamine; S/N) at residue 128 in the C1 domain. Here we show that the 267 N/Q substitution causes the abnormal exposure of a segment of C1 spanning residues 80 to 120, which compromises the integrity of the CD4-binding site. The reversion substitution at residue 128 restores the normal conformation of the C1 domain and recreates a high-affinity CD4-binding site. The gp120 structural perturbation caused by changes in C2 extends also to the C5 domain, and we show by immunological analysis that there is a close association between areas of the C1 and C5 domains. This association might be important for forming a complex binding site for gp41 (E. Helseth, U. Olshevsky, C. Furman, and J. Sodroski. J. Virol. 65:2119-2123, 1991). Segments of the C1 and C2 domains are predicted to form amphipathic alpha helices. We suggest that these helices might be packed together in the core of the folded gp120 molecule, that the 267 N/Q substitution disrupts this interdomain association, and that the 128 S/N reversion substitution restores it. C1 NIAID,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT MICROBIOL & IMMUNOL,BALTIMORE,MD 21201. UNIV CONNECTICUT,DEPT PAEDIAT,STORRS,CT 06030. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. RP MOORE, JP (reprint author), NYU,SCH MED,AARON DIAMOND AIDS RES CTR,455 1ST AVE,NEW YORK,NY 10016, USA. FU NIAID NIH HHS [AI25862, AI30358, AI36082] NR 46 TC 77 Z9 77 U1 0 U2 2 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 NOV PY 1994 VL 68 IS 11 BP 6836 EP 6847 PG 12 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600002 PM 7933065 ER PT J AU RALPH, WM CABATINGAN, MS SCHAFFER, PA AF RALPH, WM CABATINGAN, MS SCHAFFER, PA TI INDUCTION OF HERPES-SIMPLEX VIRUS TYPE-1 IMMEDIATE-EARLY GENE-EXPRESSION BY A CELLULAR-ACTIVITY EXPRESSED IN VERO AND NB41A3 CELLS AFTER GROWTH ARREST-RELEASE SO JOURNAL OF VIROLOGY LA English DT Article ID LATENCY-ASSOCIATED TRANSCRIPT; MOUSE NEUROBLASTOMA-CELLS; NEURO-BLASTOMA CELLS; DNA-SEQUENCES; MESSENGER-RNA; MACROMOLECULAR-SYNTHESIS; DELETION MUTANTS; INFECTED MICE; PROMOTER; PROTEIN AB Infected cell protein 0 (ICP0), a major immediate-early regulatory protein of herpes simplex virus type 1 (HSV-1), activates expression of all classes of HSV genes as well as a variety of heterologous viral and cellular genes. Previous studies have shown that a cellular activity expressed maximally in Vero cells 8 h after release from growth arrest in the G(0)/G(1), phase of the cell cycle can enhance plaque formation and gene expression of a mutant virus (7134) lacking both copies of the gene encoding ICPO (W. Cai and P. Schaffer, J. Virol. 65:4078-4090, 1991). This observation suggests that the cellular activity can substitute for ICPO to activate viral gene expression. To further characterize this cellular activity, Vero and NB41A3 (mouse neuroblastoma) cells were transfected at various times after release from growth arrest with promoter-chloramphenicol acetyltransferase (CAT) constructs containing promoters representing the major kinetic classes of HSV genes, and CAT activity was measured from 2 to 24 h postrelease. The results of these tests demonstrate that CAT expression from immediate-early promoter-CAT plasmids was enhanced 10- and 3-fold when Vero and NB41A3 cells were transfected al 6 and 2 h postrelease, respectively. In contrast, only low levels of immediate-early promoter-driven CAT activity were apparent when cells were transfected at later times postrelease. No significant stimulation of CAT activity was observed from promoter-CAT plasmids containing representative early or late HSV promoters or a heterologous viral (simian virus 40 early) promoter. Differences in the efficiency of uptake of plasmid DNA by cells at various times postrelease did not account for the observed differences in CAT expression. Unlike Vero cells, in which cell division resumed after release from growth arrest, division of NB41A3 cells did not resume. Rather, these cells displayed morphological features suggestive of a differentiated phenotype. Collectively, these findings demonstrate that a cellular activity expressed in Vero and NB41A3 cells after release from growth arrest can activate HSV gene expression by enhancing immediate-early gene expression. C1 DANA FARBER CANC INST,DIV MOLEC GENET,TUMOR VIRUS GENET LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NCI NIH HHS [R37 CA20260]; NIAID NIH HHS [P01 AI24010]; NIGMS NIH HHS [T32 GM11676] NR 81 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1994 VL 68 IS 11 BP 6871 EP 6882 PG 12 WC Virology SC Virology GA PL736 UT WOS:A1994PL73600005 PM 7933067 ER PT J AU CAPLAN, D HILDEBRANDT, N WATERS, GS AF CAPLAN, D HILDEBRANDT, N WATERS, GS TI INTERACTION OF VERB SELECTIONAL RESTRICTIONS, NOUN ANIMACY AND SYNTACTIC FORM IN SENTENCE PROCESSING SO LANGUAGE AND COGNITIVE PROCESSES LA English DT Article ID PARSING STRATEGIES; COMPREHENSION; CONSTRAINTS; INFORMATION; APHASIA; CONTEXT AB We report five experiments that deal with the role of verb selectional restrictions and the animacy of nouns in the construction and interpretation of syntactic structure. In the first two experiments, the effect of the selectional restriction requirements of verbs and the animacy of nouns on sentence comprehension was assessed in a speeded acceptability judgement task. Four sentence types were presented in which syntactic complexity (object vs subject relativisation) and number of propositions were orthogonally varied. Sentences contained verbs that required either animate subjects or animate objects, and unacceptable sentences were created by violating the selectional restriction requirements of the verb in the embedded clause. Analyses of both reaction time and accuracy data showed that there was an interaction between the selectional restriction requirements of verbs (which correlated perfectly with the animacy of nouns in subject or object position), and syntactic form, on these judgements. Experiment 3 was designed to determine whether the interaction found in the first set of studies was due to the selectional restriction requirements of the verbs or the animacy of nouns in particular grammatical positions. Cleft-subject and cleft-object sentences containing verbs that imposed selectional restrictions, in which animacy of nouns was varied, were presented in a speeded acceptability judgement task. The results indicated that the interaction between type of selectional restriction (imposed on the subject vs on the object) and syntactic structure only held for sentences with pairs of nouns that varied in animacy. Experiments 4 and 5 were self-paced reading experiments that were designed to determine where in the course of sentence processing this interaction between the animacy of the nouns in particular grammatical positions and the syntactic form of a sentence occurred. Tn both experiments, subjects read deft-object sentences in which the animacy of the matrix noun and the noun in subject position of the relative clause was varied, and the verbs selected for either animate subjects or animate objects, In both experiments, there were no differences in self-paced reading times until the presentation of the verb of the embedded clause, at which point there were significant differences as a function of verb type. These experiments indicate that the selectional restriction requirements of a verb and the animacy of a noun in subject and object positions interact with the syntactic form of a sentence at some stage of the sentence comprehension process. The results are discussed in terms of the architecture of the parser and the issue of the modularity of the sentence comprehension system. C1 MCGILL UNIV,SCH HUMAN COMMUN DISORDERS,MONTREAL,PQ,CANADA. RP CAPLAN, D (reprint author), MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,VINCENT BURNHAM 827,FRUIT ST,BOSTON,MA 02114, USA. NR 52 TC 38 Z9 38 U1 3 U2 3 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0169-0965 J9 LANG COGNITIVE PROC JI Lang. Cogn. Process. PD NOV PY 1994 VL 9 IS 4 BP 549 EP 585 DI 10.1080/01690969408402131 PG 37 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA PW169 UT WOS:A1994PW16900003 ER PT J AU GOLDSTRAW, P ROCMANS, P BALL, D BARTHELEMY, N BONNER, J CARETTE, M CHOI, N EMAMI, B GRUNENWALD, D HAZUKA, M IHDE, D JASSEM, J KHO, G LECHEVALIEIR, T MONTEAU, M STORME, G WAGENAAR, S AF GOLDSTRAW, P ROCMANS, P BALL, D BARTHELEMY, N BONNER, J CARETTE, M CHOI, N EMAMI, B GRUNENWALD, D HAZUKA, M IHDE, D JASSEM, J KHO, G LECHEVALIEIR, T MONTEAU, M STORME, G WAGENAAR, S TI PRETREATMENT MINIMAL STAGING FOR NONSMALL CELL LUNG-CANCER - AN UPDATED CONSENSUS REPORT SO LUNG CANCER LA English DT Article; Proceedings Paper CT 3rd IASLC Workshop on Therapy of Non-Small Cell Lung Cancer - Controversies in Staging and Treatment of Locally Advanced Non-Small Cell Lung Cancers CY AUG 29-SEP 02, 1993 CL BRUGGE, BELGIUM SP INT ASSOC STUDY LUNG CANC C1 HOSP ERASME, BRUSSELS, BELGIUM. PETER MACCALLUM CANC INST, MELBOURNE, FL USA. UNIV LIEGE, CTR HOSP, LIEGE, BELGIUM. MAYO CLIN & MAYO FDN, ROCHESTER, MN USA. HOP TENON, PARIS, FRANCE. MASSACHUSETTS GEN HOSP, BOSTON, MA USA. WASHINGTON UNIV, MED CTR, ST LOUIS, MO USA. SERV CHIRURG THORAC, PARIS, FRANCE. UNIV MICHIGAN, ANN ARBOR, MI USA. NATL NAVAL MED CTR, BETHESDA, MD USA. MED ACAD GDANSK, GDANSK, POLAND. ACAD ZIEKENHUIS ROTTERDAM, ROTTERDAM, NETHERLANDS. INST GUSTAVE ROUSSY, VILLEJUIF, FRANCE. POLYCLIN COURLANCY, REIMS, FRANCE. FREE UNIV BRUSSELS, ACAD ZIEKENHUIS, JETTE, BELGIUM. UNIV LIMBURG, MAASTRICHT, NETHERLANDS. RP GOLDSTRAW, P (reprint author), ROYAL BROMPTON HOSP, DEPT THORAC SURG, LONDON SW3 6NP, ENGLAND. NR 0 TC 9 Z9 9 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 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD NOV PY 1994 VL 11 SU 3 BP S1 EP S4 DI 10.1016/0169-5002(94)91856-2 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA QE251 UT WOS:A1994QE25100001 PM 7704500 ER PT J AU GREEN, MR GINSBERG, R ARDIZZONI, A CHOI, N DARWISH, S FUKUOKA, M GINER, V GRUNENWALD, D HARPER, P KHO, S LECHEVALIER, T LEWINSKI, T PAYNE, D POSTMUS, P ROCMANS, P ROSELL, R ROTH, J SCULIER, JP SORENSEN, JB AF GREEN, MR GINSBERG, R ARDIZZONI, A CHOI, N DARWISH, S FUKUOKA, M GINER, V GRUNENWALD, D HARPER, P KHO, S LECHEVALIER, T LEWINSKI, T PAYNE, D POSTMUS, P ROCMANS, P ROSELL, R ROTH, J SCULIER, JP SORENSEN, JB TI INDUCTION THERAPY FOR STAGE-III NSCLC - A CONSENSUS REPORT SO LUNG CANCER LA English DT Article; Proceedings Paper CT 3rd IASLC Workshop on Therapy of Non-Small Cell Lung Cancer - Controversies in Staging and Treatment of Locally Advanced Non-Small Cell Lung Cancers CY AUG 29-SEP 02, 1993 CL BRUGGE, BELGIUM SP INT ASSOC STUDY LUNG CANC C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY. MASSACHUSETTS GEN HOSP,BOSTON,MA. INST GUSTAVE ROUSSY,VILLEJUIF,FRANCE. ACAD ZIEKENHUIS ROTTERDAM,ROTTERDAM,NETHERLANDS. SERV CHIRURG THORAC,PARIS,FRANCE. HOSP ERASME,BRUSSELS,BELGIUM. GUYS HOSP,LONDON,ENGLAND. HOSP BARCELONA GERMANS TRIAS & PUJOL BARCELONA,BARCELONA,SPAIN. HOSP DR PESET,UNIDAD ONCOL MED,VALENCIA,SPAIN. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT THORAC SURG,HOUSTON,TX 77030. RIGSHOSP,DEPT ONCOL,DK-2100 COPENHAGEN,DENMARK. UNIV TEXAS,MD ANDERSON CANCER CTR,DEPT TUMOR BIOL,HOUSTON,TX 77030. PRINCESS MARGARET HOSP,TORONTO,ON,CANADA. INST JULES BORDET,BRUSSELS,BELGIUM. RP GREEN, MR (reprint author), UNIV CALIF SAN DIEGO,MED CTR,200 W ARBOR DR 8421,SAN DIEGO,CA 92103, USA. NR 3 TC 8 Z9 8 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 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD NOV PY 1994 VL 11 SU 3 BP S9 EP S10 DI 10.1016/0169-5002(94)91858-9 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA QE251 UT WOS:A1994QE25100003 PM 7704518 ER PT J AU KATZ, JN GELBERMAN, RH WRIGHT, EA LEW, RA LIANG, MH AF KATZ, JN GELBERMAN, RH WRIGHT, EA LEW, RA LIANG, MH TI RESPONSIVENESS OF SELF-REPORTED AND OBJECTIVE MEASURES OF DISEASE SEVERITY IN CARPAL-TUNNEL SYNDROME SO MEDICAL CARE LA English DT Article DE RESPONSIVENESS; CARPAL TUNNEL SYNDROME; FUNCTIONAL STATUS MEASURES; EFFECT SIZE ID HEALTH-STATUS INSTRUMENTS; SENSITIVITY; ARTHRITIS; OUTCOMES AB Responsiveness, the ability to detect meaningful clinical change, is a critical attribute of instruments used to evaluate outcomes of treatments. The authors hypothesized that self-administered symptom severity and functional status questionnaires are more responsive to clinical improvement after carpal tunnel release than traditional physical examination measures of strength and sensibility. Data were obtained from a randomized clinical trial of endoscopic versus open carpal tunnel release conducted in four university medical centers. Patients were evaluated before surgery and 3 months after surgery. Seventy-four patients indicating that they were more than 80% satisfied with the results of surgery were assumed to have clinically meaningful improvement and were the focus of the analysis. Evaluations included questionnaires assessing symptom severity, functional status, and activities of daily living as well as measurement of grip, pinch, and abductor pollicus brevis strength, and 2-point discrimination and Semmes-Weinstein pressure sensibility. Responsiveness was calculated with the standardized response mean (mean change/standard deviation of change) as well as the effect size (mean change/standard deviation of baseline values). The symptom severity scale was four times as responsive, and the functional status and activities of daily living scales were twice as responsive, as the measures of strength and sensibility. Self-administered symptom severity and functional status scales are much more responsive to clinical improvement than measures of neuromuscular impairment and should serve as primary outcomes in clinical studies of therapy for carpal tunnel syndrome. C1 ROBERT B BRIGHAM MULTIPURPOSE ARTHRITIS & MUSCULOSKELETAL DIS CTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. RP KATZ, JN (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIAMS NIH HHS [AR36308] NR 28 TC 97 Z9 98 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 1994 VL 32 IS 11 BP 1127 EP 1133 DI 10.1097/00005650-199411000-00005 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA PQ530 UT WOS:A1994PQ53000005 PM 7967853 ER PT J AU FLEISCHER, DE GRIMM, IS FRIEDMAN, LS AF FLEISCHER, DE GRIMM, IS FRIEDMAN, LS TI INFLAMMATORY BOWEL-DISEASE IN OLDER PATIENTS SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID CHRONIC ULCERATIVE-COLITIS; LONG-TERM PROGNOSIS; CROHNS-DISEASE; STOCKHOLM COUNTY; CLINICAL COURSE; LATE ONSET; FOLLOW-UP; PREVALENCE; MORTALITY; EPIDEMIOLOGY AB Although inflammatory bowel disease (lBD) is considered a disease primarily of young adults, ulcerative colitis and Crohn's disease may not present until later in life, even after the age of 60 years. Late-onset IBD has become increasingly important as the number of elderly in the population has increased. By the year 2000, there will be more than 30 million elderly persons in the United States alone, and the incidence of IBD in the elderly may be rising. This article examines the unique features of IBD presenting in old age. C1 HARVARD UNIV,SCH MED,BOSTON,MA. JEFFERSON MED COLL,DEPT MED,DIV GASTROENTEROL & HEPATOL,PHILADELPHIA,PA. UNIV N CAROLINA,DEPT INTERNAL MED,DIV DIGEST DIS,CHAPEL HILL,NC. RP FLEISCHER, DE (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BULFINCH 127,BOSTON,MA 02114, USA. NR 105 TC 31 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD NOV PY 1994 VL 78 IS 6 BP 1303 EP 1319 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA PT349 UT WOS:A1994PT34900008 PM 7967911 ER PT J AU FERBER, S MEYEROVITCH, J KRIAUCIUNAS, KM KAHN, CR AF FERBER, S MEYEROVITCH, J KRIAUCIUNAS, KM KAHN, CR TI VANADATE NORMALIZES HYPERGLYCEMIA AND PHOSPHOENOLPYRUVATE CARBOXYKINASE MESSENGER-RNA LEVELS IN OB/OB MICE SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID GLUCOSE TRANSPORTER; SKELETAL-MUSCLE; RAT ADIPOCYTES; DIABETIC RATS; MESSENGER-RNA; GENE-TRANSCRIPTION; GLYCOGEN-SYNTHASE; ENZYME ACTIVITIES; ION INHIBITION; BLOOD-GLUCOSE AB Oral vanadate administration has been demonstrated to normalize blood glucose levels in ob/ob and db/db mice and streptozotocin (STZ) diabetic rats. The exact mechanism of this vanadate effect is uncertain, since there are no consistent effects on the insulin receptor tyrosine kinase activity or phosphotyrosine phosphatase activity. We have therefore studied the postreceptor actions of vanadate, focusing our attention on the steady-state levels of mRNA of enzymes involved in carbohydrate metabolism. When compared with their lean (ob/+) controls, the livers of ob/ob mice exhibited an approximately 90% reduction in the levels of phosphoenolpyruvate carboxykinase (PEPCK) mRNA and twofold to fivefold higher levels of the mRNAs for glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the ''liver beta-cell'' glucose transporter (GLUT2), and the proto-oncogene c-myc. Administration of sodium vanadate (0.25 mg/mL) in the drinking water of ob/ob mice over a 45-day period resulted in a near normalization of blood glucose and increased PEPCK mRNA levels more than ninefold. Starvation of the ob/ob mice for 24 to 48 hours also increased PEPCK mRNA levels by fourfold to 15-fold. Vanadate treatment did not alter mRNA levels of any other proteins studied and had no effect on PEPCK mRNA in ob/+ mice. However, 1 to 100 mu mol/L vanadate produced a concentration-dependent increase in PEPCK mRNA levels in an H35 hepatoma cell line, an effect opposite to the suppression of PEPCK mRNA produced by insulin. In summary, hyperglycemia in the ob/ob mouse is characterized by decreased expression of PEPCK and increased expression of GAPDH mRNA. PEPCK mRNA levels increase during fasting, suggesting that there is some regulatory effect by the high levels of circulating insulin that appear to ovecome, at least in part, the severe insulin resistance. Vanadate treatment increases the low PEPCK mRNA level as it normalizes blood glucose. The hypoglycemic effect of vanadate cannot be explained by any action on PEPCK at the level of mRNA expression, and in fact occurs despite an effect to increase PEPCK mRNA. Interestingly, ob/ob mice do exhibit high levels of expression of GLUT2 in the liver, which may facilitate glucose efflux and thus contribute to increase hepatic glucose output. However, GLUT2 is unaffected by vanadate treatment, despite normalization of blood glucose. Copyright (C) 1994 by W.B. Saunders Company C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [DK 36836, DK 33201, DK 31036] NR 58 TC 19 Z9 20 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 1994 VL 43 IS 11 BP 1346 EP 1354 DI 10.1016/0026-0495(94)90026-4 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PR059 UT WOS:A1994PR05900004 PM 7968588 ER PT J AU KRISTJANSEN, PEG ROBERGE, S LEE, I JAIN, RK AF KRISTJANSEN, PEG ROBERGE, S LEE, I JAIN, RK TI TISSUE-ISOLATED HUMAN TUMOR XENOGRAFTS IN ATHYMIC NUDE-MICE SO MICROVASCULAR RESEARCH LA English DT Article ID INTERSTITIAL FLUID PRESSURE; BREAST CANCER XENOGRAFTS; BLOOD-FLOW; SOLID TUMORS; MICROVASCULAR ARCHITECTURE; MAGNETIC-RESONANCE; MAMMARY-CARCINOMA; PERFUSED EXVIVO; P-31 NMR; ADENOCARCINOMA AB An ex vivo perfused solid tumor preparation provides control over the physiological, biochemical, and pharmacological composition of the arterial input and easy access to the venous output. This is advantageous for studies of transport and metabolism in solid tumors. Here we present a tissue-isolated tumor preparation adapted to the nude mouse, allowing ex vivo perfusion of human tumor xenografts. Previously, such preparations have only been developed in rats, to study primarily rodent tumors. In the present study this new tumor preparation is physiologically characterized in comparison with subcutaneously transplanted tumors in nude mice using the human colon adenocarcinoma LS174T. (C) 1994 Academic Press, Inc. RP KRISTJANSEN, PEG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,STEELE LAB,COX 7,BOSTON,MA 02114, USA. FU NCI NIH HHS [R35-CA-56591] NR 32 TC 38 Z9 38 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD NOV PY 1994 VL 48 IS 3 BP 389 EP 402 DI 10.1006/mvre.1994.1063 PG 14 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA QA737 UT WOS:A1994QA73700010 PM 7731400 ER PT J AU FOSTER, R HU, KQ SHAYWITZ, DA SETTLEMAN, J AF FOSTER, R HU, KQ SHAYWITZ, DA SETTLEMAN, J TI P190 RHOGAP, THE MAJOR RASGAP-ASSOCIATED PROTEIN, BINDS GTP DIRECTLY SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GUANINE-NUCLEOTIDE-BINDING; ELONGATION-FACTOR TU; ACTIVATING PROTEIN; TRIPHOSPHATE CONFORMATION; TYROSINE KINASES; FACTOR-TS; GAP; DOMAIN; P21; HYDROLYSIS AB In mitogenically stimulated cells, a specific complex forms between the pas GTPase-activating protein (RasGAP) and the cellular protein p190. We have previously reported that p190 contains a carboxy-terminal domain that functions as a GAP for the Rho family GTPases. Thus, the RasGAP-p190 complex may serve to couple Ras- and Rho-mediated signalling pathways. In addition to its RhoGAP domain, p190 contains an amino-terminal domain that contains sequence motifs found in all known GTPases. Here, we report that p190 binds GTP and GDP through this conserved domain and that the structural requirements for binding are similar to those seen with other GTPases. While the purified protein is unable to hydrolyze GTP, we detect an activity in cell lysates that can promote GTP hydrolysis by p190. A mutated form of p190 that fails to bind nucleotide retains its RasGAP binding and RhoGAP activities, indicating that GTP binding by p190 is not required for these functions. The sequence of p190 in the GTP-binding domain, which shares structural features with both the Ras-like small GTPases and the larger G proteins, suggests that this protein defines a novel class of guanine nucleotide-binding proteins. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 39 TC 46 Z9 46 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 NOV PY 1994 VL 14 IS 11 BP 7173 EP 7181 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PM684 UT WOS:A1994PM68400015 PM 7935432 ER PT J AU TSUKADA, J SAITO, K WATERMAN, WR WEBB, AC AURON, PE AF TSUKADA, J SAITO, K WATERMAN, WR WEBB, AC AURON, PE TI TRANSCRIPTION FACTORS NF-IL6 AND CREB RECOGNIZE A COMMON ESSENTIAL SITE IN THE HUMAN PROINTERLEUKIN 1-BETA GENE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; PHOSPHOENOLPYRUVATE CARBOXYKINASE GTP; ELEMENT-BINDING PROTEIN; CYCLIC-AMP; DNA-BINDING; C/EBP FAMILY; SOMATOSTATIN GENE; NUCLEAR FACTOR; PHOSPHORYLATION; CAMP AB A site located between -2782 and -2729 of the human prointerleukin-1 beta (IL1B) gene functions as a strong lipopolysaccharide (LPS)-responsive enhancer independent of the previously identified enhancer located between -2896 and -2846 (F. Shirakawa, K. Saito, C.A. Bonagura, D. L. Galson, M. J. Fenton, A. C. Webb, and P. E. Auron, Mol. Cell. Biol. 13:1332-1344, 1993). Although these two enhancers appear to function cooperatively in the native sequence context, they function independently as LPS-responsive elements upon removal of an interposed silencer sequence. The new enhancer is not induced by dibutyryl cyclic AMP (dbcAMP) alone but is superinduced by costimulation with LPS-dbcAMP. This pattern of induction depends upon the nature of the sequence, a composite NF-IL6-cAMP response element (CRE) binding site. This pseudosymmetrical sequence is shown to contrast with a classical symmetric CRE which responds to dbcAMP but not LPS. DNA binding studies using in vivo nuclear extract, recombinant proteins, and specific antibodies show that LPS induces the formation of two different complexes at the enhancer: (i) an NF-IL6-CREB heterodimer and (ii) a heterodimer consisting of NF-IL6 and a non-CREB, CRE-binding protein. Cotransfection studies using NF-IL6 and CREB expression vectors show that NF-IL6 transactivates the enhancer in the presence of LPS, whereas CREB acts either positively or negatively, depending upon its cAMP-regulated phosphorylation state. Our data demonstrate that the newly identified enhancer is a specialized LPS responsive sequence which can be modulated by cAMP as a result of the involvement of NF-IL6-CRE-binding protein heterodimers. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. WELLESLEY COLL,DEPT BIOL SCI,WELLESLEY,MA 02181. FU NIAID NIH HHS [AI27850] NR 49 TC 141 Z9 143 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 NOV PY 1994 VL 14 IS 11 BP 7285 EP 7297 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PM684 UT WOS:A1994PM68400027 PM 7935442 ER PT J AU TAN, Y LOW, KG BOCCIA, C GROSSMAN, J COMB, MJ AF TAN, Y LOW, KG BOCCIA, C GROSSMAN, J COMB, MJ TI FIBROBLAST GROWTH-FACTOR AND CYCLIC-AMP (CAMP) SYNERGISTICALLY ACTIVATE GENE-EXPRESSION AT A CAMP RESPONSE ELEMENT SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN KINASE-A; PREPROENKEPHALIN MESSENGER-RNA; GLUTATHIONE-S-TRANSFERASE; C-JUN; NERVOUS-SYSTEM; TRANSCRIPTIONAL ACTIVATION; PROENKEPHALIN EXPRESSION; CELL-PROLIFERATION; MOUSE FIBROBLASTS; CATALYTIC SUBUNIT AB Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act synergistically to stimulate proenkephalin gene expression. Positive synergy between growth factors and cAMP-activated signaling pathways on gene expression has not been previously reported, and we suggest that these synergistic interactions represent a useful model for analyzing interactions between these pathways. Transfection and mutational studies indicate that both FGF-dependent gene activation and cAMP-dependent gene activation require cAMP response element 2 (CRE-2), a previously characterized cAMP-dependent regulatory element. Furthermore, multiple copies of this element are sufficient to confer FGF regulation upon a minimal promoter, indicating that FGF and cAMP signaling converge upon transcription factors acting at CRE-2. Among many different ATF/AP-1 factors tested, two factors, ATF-3 and c-Jun, stimulate proenkephalin transcription in an FGF- or Pas-dependent fashion. Finally, we show that ATF-3 and c-Jun form heterodimeric complexes in SK-N-MC cells and that the levels of both proteins are increased in response to FGF but not cAMP. Together, these results indicate that growth factor- and cAMP-dependent signaling pathways converge at CRE-2 to synergistically stimulate gene expression and that ATF-3 and c-Jun regulate proenkephalin transcription in response to both growth factor- and cAMP-dependent intracellular signaling pathways. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROBIOL LAB,BOSTON,MA 02129. FU NIDA NIH HHS [DA 05706, DA 0151] NR 68 TC 42 Z9 42 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 NOV PY 1994 VL 14 IS 11 BP 7546 EP 7556 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PM684 UT WOS:A1994PM68400055 PM 7935470 ER PT J AU BISWAS, DK AHLERS, CM DEZUBE, BJ PARDEE, AB AF BISWAS, DK AHLERS, CM DEZUBE, BJ PARDEE, AB TI PENTOXIFYLLINE AND OTHER PROTEIN-KINASE-C INHIBITORS DOWN-REGULATE HIV-LTR NF-KAPPA-B INDUCED GENE-EXPRESSION SO MOLECULAR MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; LONG TERMINAL REPEAT; TRANSCRIPTION FACTOR; SELECTIVE INHIBITOR; T-CELLS; BINDING PROTEIN; CALPHOSTIN-C; ACTIVATION; POTENT AB Background: This investigation deals with the molecular mechanism of anti-human immunodeficiency virus type 1 (HIV-1) action of pentoxifylline (PTX) [1-(5'-oxohexyl)-3,7-dimethylxanthine] a drug widely used for the treatment of conditions involving defective regional microcirculation. Materials and Methods: The inhibition by PTX of protein kinase C (PKC) or cAMP-dependent protein kinase (PKA)-mediated activation by phorbol ester (PMA) and tumor necrosis factor alpha (TNF-alpha) of HIV-1-LTR-regulated reporter gene expression was studied in human CD4(+) T lymphocytes (Jurkat) and human embryo kidney cells (293-27-2). A protein kinase C is involved in activation of NF-kappa B in whole cells, identified by using inhibitors specific for PKC- or PKA-catalyzed NF-kappa B activation in whole cell and cell-free systems. Results: PTX inhibited PKC- or PKA-catalyzed activation of NF-kappa B in cytoplasmic extracts from unstimulated Jurkat or 293-27-2 cells, but not interaction of preactivated NF-kappa B with its motifs. Calphostin C, a specific inhibitor of PKC, inhibited NF-kappa B activation and HIV-1 LTR-driven reporter gene expression in both PMA- and TNF-alpha-treated cells. In contrast, although H88 specifically inhibited PKA activity in the cell-free extract, it did not affect NF-kappa B action in PMA-or TNF-alpha-treated cells. Conclusions: The mechanism of inhibitory action of PTX on virus replication and NF-kappa B-induced transactivation of HIV-1 gene expression has been elucidated as due to blocking PKC-dependent PMA- or TNF-alpha-induced activation of NF-kappa B in Jurkat and 293-27-2 cells. Other protein kinase inhibitors may be useful in down regulating transcription of HIV-1 provirus and thereby virus replication in HIV-infected patients. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP BISWAS, DK (reprint author), DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,DANA 810,44 BINNEY ST,BOSTON,MA 02115, USA. NR 47 TC 32 Z9 33 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD NOV PY 1994 VL 1 IS 1 BP 31 EP 43 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA QX598 UT WOS:A1994QX59800005 PM 8790599 ER PT J AU BANGA, SS HALL, KT SANDHU, AK WEAVER, DT ATHWAL, RS AF BANGA, SS HALL, KT SANDHU, AK WEAVER, DT ATHWAL, RS TI COMPLEMENTATION OF V(D)J RECOMBINATION DEFECT AND X-RAY-SENSITIVITY OF SCID MOUSE CELLS BY HUMAN-CHROMOSOME-8 SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE DOUBLE-STRAND BREAK; X-RAY SENSITIVITY; DNA REPAIR; V(D)J RECOMBINATION ID COMBINED IMMUNE-DEFICIENCY; STRAND BREAK REPAIR; IONIZING-RADIATION; DNA-REPAIR; MUTATION; GENE; REARRANGEMENT; MICE; LOCALIZATION; THYMOCYTES AB Cells derived from mice homozygous for the severe combined immune deficiency (scid) mutation exhibit hypersensitivity to ionizing radiation, and defects in DNA double-strand break repair and V(D)J recombination. Using the technique of microcell-mediated chromosome transfer, we have introduced a number of dominantly marked human chromosomes into scid cells to localize the human homolog of the murine scid gene. Analysis of human-scid hybrid clones revealed that the presence of human chromosome 8 partially restored accurate V(D)J recombination and radioresistance to scid cells. Subsequent loss of the human chromosome 8 from human-scid hybrid clones rendered these cells sensitive to gamma-radiation and impaired their ability to catalyse V(D)J recombination. Introduction of chromosomes 2, 14, 16 and 19 that encode other repair genes did not result in the correction of these two scid defects. These observations demonstrate that the human homolog of the mouse scid gene resides on human chromosome 8. 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. RP BANGA, SS (reprint author), UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT MICROBIOL & MOLEC GENET,185 S ORANGE AVE,NEWARK,NJ 07103, USA. FU NCI NIH HHS [CA54326] NR 25 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD NOV PY 1994 VL 315 IS 3 BP 239 EP 247 DI 10.1016/0921-8777(94)90035-3 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA PP144 UT WOS:A1994PP14400004 PM 7526201 ER PT J AU OZELIUS, LJ BREAKEFIELD, XO AF OZELIUS, LJ BREAKEFIELD, XO TI COFACTOR INSUFFICIENCY IN DYSTONIA-PARKINSONIAN SYNDROME SO NATURE GENETICS LA English DT Editorial Material ID CYCLOHYDROLASE-I DEFICIENCY; DOPA-RESPONSIVE DYSTONIA; HYPERPHENYLALANINEMIA; BIOPTERIN; FAMILY; LOCUS C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RP OZELIUS, LJ (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114, USA. NR 28 TC 11 Z9 11 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1994 VL 8 IS 3 BP 207 EP 209 DI 10.1038/ng1194-207 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA PP765 UT WOS:A1994PP76500002 PM 7874157 ER PT J AU SHERIFF, S CHANG, CYY EZEKOWITZ, RAB AF SHERIFF, S CHANG, CYY EZEKOWITZ, RAB TI HUMAN MANNOSE-BINDING PROTEIN CARBOHYDRATE-RECOGNITION DOMAIN TRIMERIZES THROUGH A TRIPLE ALPHA-HELICAL COILED-COIL SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID COMPLEMENT PATHWAY; CLASSICAL PATHWAY; LECTINS; FORMS; RAT; ASSOCIATION; SALMONELLA; RECEPTOR; INVITRO; VIRUS AB Human mannose-binding protein is a hexamer of trimers with each subunit consisting of an amino-terminal region rich in cysteine, 19 collagen repeats, a 'neck', and a carbohydrate recognition domain that requires calcium to bind ligand. A 148-residue peptide, consisting of the 'neck' and carbohydrate recognition domains forms trimers in solution and in crystals. The structure of this trimeric peptide has been determined in two different crystal forms. The 'neck' forms a triple alpha-helical coiled-coil. Each alpha-helix interacts with a neighbouring carbohydrate recognition domain. The spatial arrangement of the carbohydrate recognition domains suggest how MBP trimers form the basic recognition unit for branched oligosaccharides on microorganisms. C1 HARVARD UNIV,CHILDRENS HOSP,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP SHERIFF, S (reprint author), BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,POB 4000,PRINCETON,NJ 08543, USA. NR 36 TC 170 Z9 177 U1 1 U2 18 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD NOV PY 1994 VL 1 IS 11 BP 789 EP 794 DI 10.1038/nsb1194-789 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA QN708 UT WOS:A1994QN70800012 PM 7634089 ER PT J AU HAUW, JJ DANIEL, SE DICKSON, D HOROUPIAN, DS JELLINGER, K LANTOS, PL MCKEE, A TABATON, M LITVAN, I AF HAUW, JJ DANIEL, SE DICKSON, D HOROUPIAN, DS JELLINGER, K LANTOS, PL MCKEE, A TABATON, M LITVAN, I TI PRELIMINARY NINDS NEUROPATHOLOGIC CRITERIA FOR STEELE-RICHARDSON-OLSZEWSKI SYNDROME (PROGRESSIVE SUPRANUCLEAR PALSY) SO NEUROLOGY LA English DT Review ID MULTIPLE SYSTEM ATROPHY; LEWY BODY DISEASE; ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMISTRY; IDIOPATHIC PARKINSONS-DISEASE; TAU-POSITIVE GLIA; NEUROFIBRILLARY TANGLES; ALZHEIMERS-DISEASE; SENILE DEMENTIA; POSTENCEPHALITIC PARKINSONISM; CORTICOBASAL DEGENERATION AB We present the preliminary neuropathologic criteria for progressive supranuclear palsy (PSP) as proposed at a workshop held at the National Institutes of Health, Bethesda, MD, April 24 and 25, 1993. The criteria distinguish typical, atypical, and combined PSP. A semiquantitative distribution of neurofibrillary tangles is the basis for the diagnosis of PSP. A high density of neurofibrillary tangles and neuropil threads in the basal ganglia and brainstem is crucial for the diagnosis of typical PSP. Tau-positive astrocytes or their processes in areas of involvement help to confirm the diagnosis. Atypical cases of PSP are variants in which the severity or distribution of abnormalities deviates from the typical pattern. Criteria excluding the diagnosis of typical and atypical PSP are large or numerous infarcts, marked diffuse or focal atrophy, Lewy bodies, changes diagnostic of Alzheimer's disease, oligodendroglial argyrophilic inclusions, Pick bodies, diffuse spongiosis, and prion protein-positive amyloid plaques. The diagnosis of combined PSP is proposed when other neurologic disorders exist concomitantly with PSP. C1 INST NEUROL,PARKINSONS DIS SOC,BRAIN TISSUE BANK,LONDON WC1N 3BG,ENGLAND. INST NEUROL,DEPT NEUROPATHOL,LONDON WC1N 3BG,ENGLAND. ALBERT EINSTEIN COLL MED,DEPT NEUROPATHOL,BRONX,NY 10467. STANFORD SCH MED,DEPT PATHOL NEUROPATHOL,SAN FRANCISCO,CA. LUDWIG BOLTZMANN INST CLIN NEUROBIOL,VIENNA,AUSTRIA. INST PSYCHIAT,DEPT NEUROPATHOL,LONDON SE5 8AF,ENGLAND. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. CASE WESTERN RESERVE UNIV,DIV NEUROPATHOL,CLEVELAND,OH 44106. NINCDS,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. RP HAUW, JJ (reprint author), HOP LA PITIE SALPETRIERE,INSERM,U360,LAB NEUROPATHOL RAYMOND ESCOUROLLE,47 BD HOP,F-75651 PARIS 13,FRANCE. OI Dickson, Dennis W/0000-0001-7189-7917; Litvan, Irene/0000-0002-3485-3445 NR 60 TC 517 Z9 521 U1 0 U2 12 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1994 VL 44 IS 11 BP 2015 EP 2019 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA PR095 UT WOS:A1994PR09500005 PM 7969952 ER PT J AU REPPERT, SM TSAI, T ROCA, AL SAUMAN, I AF REPPERT, SM TSAI, T ROCA, AL SAUMAN, I TI CLONING OF A STRUCTURAL AND FUNCTIONAL HOMOLOG OF THE CIRCADIAN CLOCK GENE PERIOD FROM THE GIANT SILKMOTH ANTHERAEA-PERNYI SO NEURON LA English DT Article ID DROSOPHILA PERIOD; NUCLEAR-PROTEIN; VISUAL-SYSTEM; PRODUCT; PACEMAKER; RECEPTOR; SEQUENCE; ANTIBODY; REVEALS; ENCODES AB The period (per) gene of Drosophila plays an important role in circadian clock function. Interestingly, homologs of per have not been cloned outside of dipteran species. Using a PCR strategy, we now report the cloning of the cDNA of a per homolog from the silkmoth Antheraea pernyi. The cDNA encodes a protein of 849 amino acids, which shows highest identity (39%) with the per protein of Drosophila virilis. Stretches of high identity between moth and fly proteins are in the amino terminus, the PAS region, and the region surrounding the site of the per(s) mutation in Drosophila. Moth per homolog mRNA levels exhibit a prominent circadian variation in adult heads, and per protein antibodies show a pronounced variation of per antigen staining in photoreceptor nuclei. With sequence information derived from moth and flies, per-like cDNA fragments were readily cloned by PCR from other moth species and a third insect order. C1 WESLEYAN UNIV,DEPT BIOL,MIDDLETOWN,CT 06459. RP REPPERT, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PROGRAM NEUROSCI,CHILDRENS SERV,DEV CHRONOBIOL LAB,BOSTON,MA 02114, USA. RI Sauman, Ivo/H-2071-2014 FU NIDDK NIH HHS [DK42125] NR 33 TC 121 Z9 127 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1994 VL 13 IS 5 BP 1167 EP 1176 DI 10.1016/0896-6273(94)90054-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA PU763 UT WOS:A1994PU76300012 PM 7946353 ER PT J AU REPPERT, SM WEAVER, DR EBISAWA, T AF REPPERT, SM WEAVER, DR EBISAWA, T TI CLONING AND CHARACTERIZATION OF A MAMMALIAN MELATONIN RECEPTOR THAT MEDIATES REPRODUCTIVE AND CIRCADIAN RESPONSES SO NEURON LA English DT Article ID OVINE PARS TUBERALIS; BINDING-SITES; SIGNAL TRANSDUCTION; JET-LAG; BRAIN; INHIBITION; HAMSTER; CYCLASE; SYSTEMS; CLOCK AB The pineal hormone melatonin regulates seasonal reproductive function and modulates circadian rhythms in mammals. We now report the cloning and characterization of a high affinity receptor for melatonin from the sheep and human. The receptor cDNAs encode proteins that are members of a newly discovered group within the G protein-coupled receptor family. Expression of the sheep and human receptors in COS-7 cells results in high affinity 2-[I-125]iodomelatonin binding and pharmacological characteristics similar to endogenous high affinity receptors. Functional studies of NIH 3T3 cells stably expressing the sheep receptor show that the mammalian melatonin receptor is coupled to inhibition of adenylyl cyclase through a pertussis toxin-sensitive mechanism. In situ hybridization studies of melatonin receptor mRNA in several mammals reveal hybridization signals in the hypophyseal pars tuberalis and hypothalamic suprachiasmatic nucleus. The cloned high affinity receptor likely mediates the reproductive and circadian actions of melatonin in mammals. RP REPPERT, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEV CHRONOBIOL LAB,BOSTON,MA 02114, USA. OI Weaver, David/0000-0001-7941-6719 FU NIDDK NIH HHS [DK42125] NR 33 TC 802 Z9 834 U1 8 U2 31 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1994 VL 13 IS 5 BP 1177 EP 1185 DI 10.1016/0896-6273(94)90055-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PU763 UT WOS:A1994PU76300013 PM 7946354 ER PT J AU LIPTON, SA STAMLER, JS AF LIPTON, SA STAMLER, JS TI ACTIONS OF REDOX-RELATED CONGENERS OF NITRIC-OXIDE AT THE NMDA RECEPTOR SO NEUROPHARMACOLOGY LA English DT Article DE NITRIC OXIDE; NITROSONIUM ION; NITROXYL ANION; NMDA RECEPTOR; REDOX; EXCITOTOXICITY ID LONG-TERM POTENTIATION; MECHANISMS; NEUROTOXICITY; MESSENGER; CULTURES; ACID AB The local redox milieu of a biological system is of critical importance in understanding the actions of the nitrogen monoxide (NO) moiety, as disparate chemical pathways involving distinct redox-related congeners of NO may trigger neurotoxic or neuroprotective pathways. The reactions of nitric oxide (NO.) with superoxide can lead to neurotoxicity through formation of peroxynitrite, whereas NO. alone does not, at least under certain conditions. Reaction (or transfer) of NO+ equivalents to thiol(s) on the NMDA receptor can lead to neuroprotection by inhibiting Ca2+ influx. These findings suggest that cell function can be controlled by, or through, protein S-nitrosylation, and raise the possibility that the NO group may initiate signal transduction in or at the plasma membrane. Neuroprotective effects of NO- suggest that acceleration of disulfide bond formation at the NMDA receptor is of mechanistic importance in the attenuation of Ca2+ influx. Our findings suggest novel therapeutic strategies. For example, downregulation of NMDA receptor activity can be obtained via sulfhydryl oxidation by S-nitros(yl)ation with NO+ donors (to form an RSNO at a cysteine residue on the receptor), or with NO- donors (with intermediate formation of RSNHOH). Pharmacologic intervention with these forms of NO donors could be implemented in the treatment of focal ischemia, neuropathic pain, Huntington's disease, AIDS dementia, and other neurological disorders associated, at least in part, with excessive activation of NMDA receptors. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. DUKE UNIV,MED CTR,DEPT MED,DIV PULM,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT MED,DIV CARDIOVASC,DURHAM,NC 27710. RP LIPTON, SA (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,CELLULAR & MOLEC NEUROSCI LAB,BOSTON,MA 02115, USA. NR 28 TC 128 Z9 135 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 1994 VL 33 IS 11 BP 1229 EP 1233 DI 10.1016/0028-3908(94)90021-3 PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA PQ856 UT WOS:A1994PQ85600003 PM 7870283 ER PT J AU DALKARA, T YOSHIDA, T IRIKURA, K MOSKOWITZ, MA AF DALKARA, T YOSHIDA, T IRIKURA, K MOSKOWITZ, MA TI DUAL ROLE OF NITRIC-OXIDE IN FOCAL CEREBRAL-ISCHEMIA SO NEUROPHARMACOLOGY LA English DT Article DE NITRIC OXIDE; CEREBRAL ISCHEMIA; L-ARGININE; NITRIC OXIDE SYNTHASE INHIBITORS; TRANSGENIC MOUSE ID RAT PIAL ARTERIOLES; L-ARGININE; ARTERY OCCLUSION; BLOOD-FLOW; BRAIN; INHIBITION; MECHANISM; SYNTHASE; INFARCTION; CGMP AB The importance of nitric oxide (NO) in the pathophysiology of cerebral ischemia was examined following middle cerebral artery occlusion in rats. A significant increase in infarct size developed following inhibition of NO synthase (NOS) activity by L-arginine analogues whereas intravenous L-arginine dose-dependently decreased infarct volume in the same models. Protection after L-arginine administration was associated with enhanced blood flow within the perinfarct zone as demonstrated by simultaneous recording of rCBF and electrocorticogram activity within subjacent brain. Selective NOS inhibition by 7-nitroindazole (7-NI) significantly reduced infarct Volume at doses of 25 and 50 mg/kg and in amounts that did not decrease the response of pial vessels to topical acetylcholine. Together these data suggest that enhanced NO production within the cerebrovasculature protects brain tissue during focal ischemia via hemodynamic mechanisms whereas neuronal overproduction may facilitate or mediate neurotoxicity. Recent data using transgenic animals lacking NOS activity support the latter conclusion. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE RES LAB,BOSTON,MA 02114. RI Moskowitz, Michael/D-9916-2011 NR 29 TC 119 Z9 124 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 1994 VL 33 IS 11 BP 1447 EP 1452 DI 10.1016/0028-3908(94)90048-5 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA PQ856 UT WOS:A1994PQ85600030 PM 7532828 ER PT J AU CHIOCCA, EA BOVIATSIS, EJ WESTMARK, RM SHORT, MP RICHARDSON, EP ZERVAS, NT AF CHIOCCA, EA BOVIATSIS, EJ WESTMARK, RM SHORT, MP RICHARDSON, EP ZERVAS, NT TI DEEP SYLVIAN FISSURE MENINGIOMA WITHOUT DURAL ATTACHMENT IN AN ADULT - CASE-REPORT SO NEUROSURGERY LA English DT Note DE DURAL ATTACHMENT,; MENINGIOMA; PRIMARY CENTRAL NERVOUS SYSTEM NEOPLASMS AB MENINGIOMAS ARE THOUGHT to arise from arachnoid cap or meningothelial cells that not only cluster on the surface of pacchionian granulations but also can cover the arachnoid membrane in other locations. This frequent apposition to the dura mater probably accounts for the usual attachment of the neoplasm to this layer. We report a deep sylvian fissure meningioma without dural attachments in the right hemisphere of an adult patient. The patient initially presented with simple partial seizures. Magnetic resonance imaging revealed a contrast-enhancing circular mass in the superior aspect of the insular region, deep to the inferior parietal lobule. Surgical exploration confirmed the absence of dural attachments. Microscopically, the tumor was found to be a sparsely cellular meningioma with an extensive collagenous matrix. A survey of the literature reveals that the majority of cases of meningiomas without dural attachments occur either in children or below the tentorium. Extremely rare cases of supratentorial meningiomas without dural attachment have been described in adults. The uncommon locations of these tumors at sites distant from the dura mater is postulated to reflect the rare occurrence of arachnoidal cap cells in the Virchow-Robin spaces along the cerebral vasculature or in pial layers distant from the dura mater. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. RP CHIOCCA, EA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,NEUROSURG SERV,BOSTON,MA 02114, USA. NR 18 TC 20 Z9 21 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 1994 VL 35 IS 5 BP 944 EP 946 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA PP102 UT WOS:A1994PP10200059 PM 7838346 ER PT J AU DELACUESTA, RS GOFF, BA FULLER, AF NIKRUI, N EICHHORN, JH RICE, LW AF DELACUESTA, RS GOFF, BA FULLER, AF NIKRUI, N EICHHORN, JH RICE, LW TI PROGNOSTIC IMPORTANCE OF INTRAOPERATIVE RUPTURE OF MALIGNANT OVARIAN EPITHELIAL NEOPLASMS - REPLY SO OBSTETRICS AND GYNECOLOGY LA English DT Letter RP DELACUESTA, RS (reprint author), MASSACHUSETTS GEN HOSP,VINCENT 1 GYNECOL,FRUIT ST,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 1994 VL 84 IS 5 BP 897 EP 897 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PN551 UT WOS:A1994PN55100037 ER PT J AU ROELKE, M JACKSON, G HARTHORNE, JW AF ROELKE, M JACKSON, G HARTHORNE, JW TI SUBMAMMARY PACEMAKER IMPLANTATION - A UNIQUE TUNNELING TECHNIQUE SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE SUBMAMMARY PACEMAKER IMPLANTATION AB Submammary pacemaker implantation offers women a cosmetically acceptable alternative to the standard pectoral implant. Mle present a novel method of submammary implantation performed on ten women aged 13-54 years. The lead electrodes are tunneled from the infraclavicular to the inframammary incision using a long needle, guidewire, and introducers/dilators in a manner analogous to the retained guidewire technique used for standard lead insertion. The procedure can generally be performed under local anesthesia. All patients tolerated the procedure well without acute complications. Over 2- to 23-month follow-up, there were no lead dislodgments. No patients developed mastitis or incisional complications, and all have been extremely satisfied with the cosmetic results. With proper technique, submammary pacemaker implantation can be performed under local anesthesia with minimal patient discomfort and optimal cosmesis. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,PACEMAKER LAB,BOSTON,MA 02114. NR 14 TC 10 Z9 10 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD NOV PY 1994 VL 17 IS 11 BP 1793 EP 1796 DI 10.1111/j.1540-8159.1994.tb03747.x PN 1 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA PR123 UT WOS:A1994PR12300012 PM 7838788 ER PT J AU ROELKE, M MCNAMARA, D OSSWALD, S SEMIGRAN, M DEC, W HARTHORNE, JW AF ROELKE, M MCNAMARA, D OSSWALD, S SEMIGRAN, M DEC, W HARTHORNE, JW TI A COMPARISON OF VVIR AND DDDR PACING FOLLOWING CARDIAC TRANSPLANTATION SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT Cardiostim 94 - Cardiac Pacing and Electrophysiology CY JUN 15-18, 1994 CL NICE, FRANCE DE VVIR; DDDR; PACEMAKER; CARDIAC TRANSPLANTATION ID ORTHOTOPIC HEART-TRANSPLANTATION; RECIPIENTS AB We compared the clinical course of patients paced in VVIR versus DDDR mode to determine the most appropriate method of pacing following cardiac transplantation. Pacemaker implantation was required in 9 of 90 orthotopic cardiac transplants (10%). Indications included sinus bradycardia or sinus arrest (8 patients) and AV node dysfunction (1 patient). VVIR pacemakers were implanted in four patients and DDDR in five patients. DDDR patients: The mean P wave was 1.7 mV and the mean atrial stimulation threshold was 0.8 V (at 0.5 msec). During follow-up of to months, two atrial lead complications developed (29% of leads in 33% of patients). No lead complications were directly related to endomyocardial biopsy. VVIR patients: All four patients developed VA conduction with mean VA time 180 msec (160-240 msec). Two patients developed pacemaker syndrome. Conclusions: VA conduction and pacemaker syndrome may develop in cardiac transplant recipients paced in the VVIR mode. Dual chamber pacing is technically feasible and preferable following cardiac transplantation. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD NOV PY 1994 VL 17 IS 11 BP 2047 EP 2051 DI 10.1111/j.1540-8159.1994.tb03798.x PN 2 PG 5 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA PR124 UT WOS:A1994PR12400041 PM 7845816 ER PT J AU LIPSHULTZ, SE SANDERS, SP COLAN, SD GOORIN, AM SALLAN, SE KRISCHER, JP AF LIPSHULTZ, SE SANDERS, SP COLAN, SD GOORIN, AM SALLAN, SE KRISCHER, JP TI THE ANTHRACYCLINE CARDIOTOXICITY DEBATE - IN REPLY SO PEDIATRICS LA English DT Letter ID THERAPY C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA 02115. UNIV S FLORIDA,H LEE MOFFITT CANC CTR & RES INST,DEPT CANC CONTROL,TAMPA,FL 33612. RP LIPSHULTZ, SE (reprint author), CHILDRENS HOSP,DEPT CARDIOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 7 TC 8 Z9 8 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 NOV PY 1994 VL 94 IS 5 BP 781 EP 782 PG 2 WC Pediatrics SC Pediatrics GA PN912 UT WOS:A1994PN91200039 ER PT J AU HARDIN, TC JENNINGS, TS AF HARDIN, TC JENNINGS, TS TI CEFEPIME SO PHARMACOTHERAPY LA English DT Article ID BROAD-SPECTRUM CEPHALOSPORIN; BETA-LACTAM ANTIBIOTICS; GRAM-NEGATIVE BACTERIA; CYSTIC-FIBROSIS PATIENTS; PSEUDOMONAS-AERUGINOSA; INVITRO ACTIVITY; HOSPITALIZED-PATIENTS; ENTEROBACTER-CLOACAE; TISSUE PENETRATION; ESCHERICHIA-COLI AB Cefepime is a potent, broad-spectrum, fourth-generation cephalosporin with enhanced activity against most gram-positive aerobic bacterial pathogens and many gram-negative aerobic bacteria that are resistant to other cephalosporins. The drug's zwitterionic structure contributes to more rapid penetration of gram-negative bacterial cell membranes, and its low affinity for most type I beta-lactamases leads to significantly reduced enzymatic degradation compared with other cephalosporins. Cefepime has a good toxicity profile, with minor gastrointestinal and central nervous system symptoms being most prevalent. At dosages ranging from 1-2 g every 8-12 hours, it is an alternative option for infections of the lower respiratory tract, urinary tract, and skin and skin structures, as well as febrile episodes in neutropenic patients with cancer, and bacteremia or septicemia in critically ill patients. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. UNIV TEXAS,COLL PHARM,AUSTIN,TX 78712. RP HARDIN, TC (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PHARM SERV 119,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 82 TC 17 Z9 18 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV-DEC PY 1994 VL 14 IS 6 BP 657 EP 668 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PU104 UT WOS:A1994PU10400002 PM 7885968 ER PT J AU JANG, JC SHEEN, J AF JANG, JC SHEEN, J TI SUGAR SENSING IN HIGHER-PLANTS SO PLANT CELL LA English DT Article ID CARBON CATABOLITE REPRESSION; INSULIN GENE-EXPRESSION; PANCREATIC BETA-CELLS; TRANSGENIC TOBACCO PLANTS; YEAST-DERIVED INVERTASE; SACCHAROMYCES-CEREVISIAE MUTANTS; DEPENDENT PROTEIN-KINASE; GLUCOSE REPRESSION; SUCROSE SYNTHESIS; SINK REGULATION AB Sugar repression of photosynthetic genes is likely a central control mechanism. mediating energy homeostasis in a wide range of algae and higher plants. It overrides light activation and is coupled to developmental and environmental regulations. How sugar signals are sensed and transduced to the nucleus remains unclear To elucidate sugar-sensing mechanisms, we monitored the effects of a variety of sugars, glucose analogs, and metabolic intermediates on photosynthetic fusion genes in a sensitive and versatile maize protoplast transient expression system. The results show that sugars that are the substrates of hexokinase (HK) cause repression at a low concentration (1 to 10 mM), indicating a low degree of specificity and the irrelevance of osmotic change. Studies with various glucose analogs suggest that glucose transport across the plasma membrane is necessary but not sufficient to trigger repression, whereas subsequent phosphorylation by HK may be required. The effectiveness of 2-deoxyglucose, a nonmetabolizable glucose analog, and the ineffectiveness of various metabolic intermediates in eliciting repression eliminate the involvement of glycolysis and other metabolic pathways. Replenishing intracellular phosphate and ATP diminished by hexoses does not overcome repression. Because mannoheptulose, a specific HK inhibitor, blocks the severe repression triggered by 2-deoxyglucose and yet the phosphorylated products per se do not act as repression signals, we propose that HK may have dual functions and may act as a key sensor end signal transmitter of sugar repression in higher plants. C1 HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT BIOL MOLEC, BOSTON, MA 02114 USA. NR 97 TC 489 Z9 534 U1 6 U2 56 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 EI 1532-298X J9 PLANT CELL JI Plant Cell PD NOV PY 1994 VL 6 IS 11 BP 1665 EP 1679 PG 15 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA PV366 UT WOS:A1994PV36600015 PM 7827498 ER PT J AU RUDKIN, GH MILLER, TA AF RUDKIN, GH MILLER, TA TI LIPEDEMA - A CLINICAL ENTITY DISTINCT FROM LYMPHEDEMA SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB In a review of 250 cases of lymphedema of the lower extremity, 9 patients were noted to share unique similarities in their history and physical findings. Although these patients had mild swelling in their pretibial areas and were all referred with a diagnosis of lymphedema of the legs, their findings differed significantly from the usual patient with either congenital or acquired lymphedema. Notably, the lower extremity swelling was always bilateral and symmetrical in nature and never involved the feet. Skin changes characteristic of lymphedema were not found, and consistent fat pads were present anterior to the lateral malleoli in each patient. These findings are representative of a clinical entity known as lipedema, which is distinct from lymphedema and for which treatment may be different. C1 UNIV CALIF LOS ANGELES,MED CTR,DIV PLAST SURG,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,PLAST SURG SECT,LOS ANGELES,CA 90073. NR 8 TC 52 Z9 53 U1 1 U2 3 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 NOV PY 1994 VL 94 IS 6 BP 841 EP 847 DI 10.1097/00006534-199411000-00014 PG 7 WC Surgery SC Surgery GA PP248 UT WOS:A1994PP24800014 PM 7972431 ER PT J AU SILVA, JA LEONG, GB AF SILVA, JA LEONG, GB TI DELUSIONS OF PSYCHOLOGICAL CHANGE OF THE SELF SO PSYCHOPATHOLOGY LA English DT Article ID CAPGRAS SYNDROME; MISIDENTIFICATION SYNDROMES; LYCANTHROPY; TOMOGRAPHY AB Delusions of psychological change of the self are becoming increasingly appreciated as a type of misidentification delusions. Most available knowledge on delusions of psychological change of the self derives from single case studies. In this article, we present a study encompassing 30 cases of this delusion. Diagnostic and phenomenologic aspects of this delusion are discussed as well as its relation to other types of misidentification delusions. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DEPT PSYCHIAT,LOS ANGELES,CA 90073. RP SILVA, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PSYCHIAT SERV 116A,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 28 TC 13 Z9 13 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0254-4962 J9 PSYCHOPATHOLOGY JI Psychopathology PD NOV-DEC PY 1994 VL 27 IS 6 BP 285 EP 290 PG 6 WC Psychiatry SC Psychiatry GA PQ634 UT WOS:A1994PQ63400004 PM 7846252 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI MEDICAL-PSYCHIATRIC PRACTICE, VOL 2 - STOUDEMIRE,A, FOGEL,BS SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GREENBERG, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 1994 VL 35 IS 6 BP 582 EP 583 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA PN752 UT WOS:A1994PN75200010 ER PT J AU GOLDSTEIN, JA AF GOLDSTEIN, JA TI CHRONIC FATIGUE SYNDROMES - THE LIMBIC HYPOTHESIS - GOLDSTEIN,JA SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GOLDSTEIN, JA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 1994 VL 35 IS 6 BP 583 EP 583 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA PN752 UT WOS:A1994PN75200011 ER PT J AU CAPLAN, D WATERS, GS AF CAPLAN, D WATERS, GS TI ARTICULATORY LENGTH AND PHONOLOGICAL SIMILARITY IN SPAN TASKS - A REPLY SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION A-HUMAN EXPERIMENTAL PSYCHOLOGY LA English DT Note ID WORD-LENGTH; MEMORY; REHEARSAL; ENGLISH AB We report a partial replication of previous results by Caplan, Rochon, and Waters (1992), using methods that address objections raised by Baddeley and Andrade (this issue) and that improve on several techniques used by them. The results cast doubts on the role of articulation in determining the word length effect in span, and hence on the role of articulation in rehearsal. RP CAPLAN, D (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPSYCHOL LAB,VINCENT BURNHAM 827,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00942] NR 9 TC 42 Z9 42 U1 1 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0272-4987 J9 Q J EXP PSYCHOL-A JI Q. J. Exp. Psychol. Sect A-Hum. Exp. Psychol. PD NOV PY 1994 VL 47 IS 4 BP 1055 EP 1062 PG 8 WC Psychology; Psychology, Experimental SC Psychology GA PT056 UT WOS:A1994PT05600011 PM 7809398 ER PT J AU PARDO, FS SU, M BOREK, C PREFFER, F DOMBKOWSKI, D GERWECK, L SCHMIDT, EV AF PARDO, FS SU, M BOREK, C PREFFER, F DOMBKOWSKI, D GERWECK, L SCHMIDT, EV TI TRANSFECTION OF RAT EMBRYO CELLS WITH MUTANT P53 INCREASES THE INTRINSIC RADIATION-RESISTANCE SO RADIATION RESEARCH LA English DT Article ID CELLULAR TUMOR-ANTIGEN; IONIZING-RADIATION; GERMLINE MUTATIONS; SKIN FIBROBLASTS; SUPPRESSOR GENE; DNA-DAMAGE; TRANSFORMATION; ONCOGENE; CANCER; RADIORESISTANCE AB Dominant oncogenic sequences have been shown to modulate the intrinsic radiation sensitivity of cells of both human and murine tumor cell lines. Whether transfection with candidate tumor-suppressor genes can modulate intrinsic radiation sensitivity is unknown. The data presented here demonstrate that transfection of rat embryo cells with a mutant p53 allele can increase the intrinsic radiation resistance of cells in vitro. First, transfection with mutant p53 resulted in transformed cellular morphology. Second, the transfected clone and the corresponding pooled population of transfected clones were more resistant to ionizing radiation in vitro. Last, analyses of the parameters of cell kinetics suggested that the radiobiological effects were unlikely to be due to altered parameters of cell kinetics at the time of irradiation, suggesting that mutant p53 altered the intrinsic radiation resistance of transfected cells by a more direct mechanism. Further experimentation will be necessary to develop a mechanistic approach for the study of these alterations. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,BOSTON,MA 02114. TUFTS UNIV,DEPT PHYSIOL,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP PARDO, FS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-13311] NR 29 TC 50 Z9 50 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 NOV PY 1994 VL 140 IS 2 BP 180 EP 185 DI 10.2307/3578901 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA PN944 UT WOS:A1994PN94400005 PM 7938466 ER PT J AU KOPANS, DB AF KOPANS, DB TI CAUTION ON CORE SO RADIOLOGY LA English DT Editorial Material DE BREAST, BIOPSY; BREAST, DISEASES; BREAST NEOPLASMS, DIAGNOSIS; DEVILS ADVOCATE ID NONPALPABLE BREAST-LESIONS; PROBABLY BENIGN LESIONS; FOLLOW-UP; BIOPSY C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,AMBULATORY CARE BLDG,STE 219,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 7 TC 62 Z9 63 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 NOV PY 1994 VL 193 IS 2 BP 325 EP 326 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PN947 UT WOS:A1994PN94700009 PM 7972737 ER PT J AU KOPANS, DB AF KOPANS, DB TI CAUTION ON CORE - REPLY SO RADIOLOGY LA English DT Editorial Material ID NONPALPABLE BREAST-LESIONS C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,AMBULATORY CARE BLDG,STE 219,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 3 TC 5 Z9 5 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 NOV PY 1994 VL 193 IS 2 BP 327 EP 328 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PN947 UT WOS:A1994PN94700011 ER PT J AU VANEVERDINGEN, KJ ENOCHS, WS BHIDE, PG NOSSIFF, N PAPISOV, M BOGDANOV, A BRADY, TJ WEISSLEDER, R AF VANEVERDINGEN, KJ ENOCHS, WS BHIDE, PG NOSSIFF, N PAPISOV, M BOGDANOV, A BRADY, TJ WEISSLEDER, R TI DETERMINANTS OF IN-VIVO MR-IMAGING OF SLOW AXONAL-TRANSPORT SO RADIOLOGY LA English DT Article; Proceedings Paper CT 1993 RSNA Scientific Assembly CY NOV 28-DEC 03, 1993 CL CHICAGO, IL SP RADIOL SOC N AMER DE MAGNETIC RESONANCE (MR), CONTRAST ENHANCEMENT; NERVES; NERVES, MR ID MAGNETIC-RESONANCE NEUROGRAPHY; IRON-OXIDE; PHARMACOKINETICS; NERVE; MEMBRANES; SURFACE AB PURPOSE: To investigate specific surface characteristics of magnetic contrast agents based on a monocrystalline iron oxide nanoparticle (MION) that may determine their uptake and/or transport by axons. MATERIALS AND METHODS: MION were modified to have a range of surface charges or were covalently linked to wheat germ agglutinin (WGA), a neurotropic protein. Each agent was injected directly into the sciatic nerves or femoral arteries of rats (n = 22), and magnetic resonance (MR) images were obtained several days later. The imaging results then were correlated with results at postmortem histologic examination. RESULTS: Substantial uptake and/or transport by axons occurred only after intraneural injection and only if the agent had a strong surface charge or was covalently linked to WGA. The sciatic nerves appeared as uniformly hypointense structures having lengths proportional to the time from injection to imaging, and the calculated transport rates (4-7 mm/d) were consistent with slow axonal transport. Numerous Schwann tells and macrophages acquired large fractions of the injected agents and contributed substantially to the imaging results. CONCLUSION: Those characteristics of MION-based contrast agents that promote efficacy after intraneural injection may impede delivery to the nerve after intraarterial injection. C1 MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,DEPT RADIOL,MR PHARMACEUT PROGRAM,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NUCL MAGNET RESONANCE CTR,DEPT NEUROL,MR PHARMACEUT PROGRAM,BOSTON,MA 02114. FU NCI NIH HHS [1ROI CA 54886-01] NR 23 TC 21 Z9 21 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1994 VL 193 IS 2 BP 485 EP 491 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PN947 UT WOS:A1994PN94700042 PM 7526413 ER PT J AU REIMER, P WEISSLEDER, R SHEN, TE KNOEFEL, WT BRADY, TJ AF REIMER, P WEISSLEDER, R SHEN, TE KNOEFEL, WT BRADY, TJ TI PANCREATIC RECEPTORS - INITIAL FEASIBILITY STUDIES WITH A TARGETED CONTRAST AGENT FOR MR-IMAGING SO RADIOLOGY LA English DT Article DE CONTRAST MEDIA, EXPERIMENTAL STUDIES; HORMONE RECEPTORS PANCREAS, NEOPLASMS; PANCREATITIS ID SUPERPARAMAGNETIC IRON-OXIDE; CHOLECYSTOKININ RECEPTOR; RAT PANCREAS; LIVER; ANTAGONISTS; HAMSTER; CANCER; MION; TIME; ECHO AB PURPOSE: To evaluate cholecystokinin (CCK) as a target-specific vector for magnetic resonance (MR) receptor imaging of rat pancreas. MATERIALS AND METHODS: Monocrystalline iron oxide (MION) was labeled with CCK by noncovalent attachment. Receptor specificity of the conjugate was determined with competitive binding studies. Pharmacologic determinations were blood half-lives, biodistribution, time responses, dose responses, and limited toxicity. RESULTS: Specific cell binding of MION-20-CCK was saturable and inhibitable by a CCK antagonist. Blood half-life of MION-20-CCK was 20 minutes, which was shorter than that of unlabeled MION. Biodistribution studies showed a statistically significant decrease in relaxation times in pancreatic tissues from 42.7 msec +/- 2.0 to 33.8 msec +/- 1.4 (P less than or equal to .05) but not in tumor after administration of MION-20-CCK. The half-life of MION-20-CCK in the pancreas was 3 weeks; no signs of toxicity were shown at the level tested. CONCLUSION: Target-specific MR imaging of pancreatic receptors is feasible. Additional studies are necessary to perfect binding strategies, optimize preparations, and scale up synthesis for imaging in other species. C1 MASSACHUSETTS GEN HOSP,MGH MNR CTR,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [R01 CA 65886-1] NR 47 TC 37 Z9 37 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1994 VL 193 IS 2 BP 527 EP 531 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PN947 UT WOS:A1994PN94700049 PM 7972773 ER PT J AU DRUCKER, EA BRENNAN, TA AF DRUCKER, EA BRENNAN, TA TI THE TURF WAR OVER PERIPHERAL VASCULAR INTERVENTION .1. SETTING THE STAGE SO RADIOLOGY LA English DT Editorial Material DE ARTERIES, TRANSLUMINAL ANGIOPLASTY; ECONOMICS, MEDICAL; RADIOLOGY AND RADIOLOGISTS, SOCIOECONOMIC ISSUES; RADIOLOGY AT LARGE ID UNITED-STATES; BYPASS-SURGERY; ANGIOPLASTY; DISEASE; RADIOLOGY; PHYSICIANS; MANAGEMENT; NONRADIOLOGISTS; AMPUTATION; MARYLAND C1 HARVARD UNIV,SCH PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BOSTON,MA. RP DRUCKER, EA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 33 TC 3 Z9 3 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1994 VL 193 IS 2 BP A81 EP A86 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PN947 UT WOS:A1994PN94700001 PM 7972788 ER PT J AU WOLLERT, PS MENCONI, MJ WANG, HL OSULLIVAN, BP LARKIN, V ALLEN, RC FINK, MP AF WOLLERT, PS MENCONI, MJ WANG, HL OSULLIVAN, BP LARKIN, V ALLEN, RC FINK, MP TI PRIOR EXPOSURE TO ENDOTOXIN EXACERBATES LIPOPOLYSACCHARIDE-INDUCED HYPOXEMIA AND ALVEOLITIS IN ANESTHETIZED SWINE SO SHOCK LA English DT Article ID TUMOR-NECROSIS-FACTOR; PLATELET-ACTIVATING-FACTOR; LUNG INJURY; RECURRENT ENDOTOXEMIA; ENDOTHELIAL-CELLS; RESPIRATORY BURST; PORCINE MODEL; NEUTROPHILS; PULMONARY; PIGS AB We sought to determine whether a standardized ''priming'' event, namely a small dose of LPS, would alter physiological responses to a subsequent larger ''challenge'' dose of endotoxin. Accordingly, four groups of pigs (N = 5-6) were studied. One group received neither priming nor challenge doses of LPS. A second group were not primed but were infused with a challenge dose (250 mu g/kg) of LPS. A third group were pretreated 18 h before being studied with a priming dose of LPS (20 mu g/kg), but were not infused with a second dose of LPS. A fourth group received both priming and challenge doses of LPS. Priming with LPS exacerbated endotoxin-induced arterial hypoxemia, and decreased animal-to-animal variability in the degree of hypoxemia induced by a challenge dose of endotoxin. Priming blunted the early phase (30 min) and exacerbated the delayed phase (120-210 min) of LPS-induced pulmonary hypertension. Priming blunted LPS-induced release of prostacyclin and thromboxane A(2). The use of a priming dose of LPS increases the severity and reproducibility of LPS-induced acute lung injury in swine. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,DEPT PEDIAT,WORCESTER,MA. EXOXEMIS INC,SAN ANTONIO,TX. RI Allen, Robert/B-6529-2008 NR 35 TC 14 Z9 14 U1 0 U2 1 PU BIOMEDICAL PRESS PI AUGUSTA PA 1021 15TH ST, BIOTECH PARK STE 9, AUGUSTA, GA 30901 SN 1073-2322 J9 SHOCK JI Shock PD NOV PY 1994 VL 2 IS 5 BP 362 EP 369 DI 10.1097/00024382-199411000-00011 PG 8 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA PP928 UT WOS:A1994PP92800009 PM 7743363 ER PT J AU CHAUNCEY, S AF CHAUNCEY, S TI EMOTIONAL CONCERNS AND TREATMENT OF MALE PARTNERS OF FEMALE SEXUAL ABUSE SURVIVORS SO SOCIAL WORK LA English DT Article DE CHILD SEXUAL ABUSE; EMOTIONAL SUPPORT; MEN; PARTNERS; WOMEN SURVIVORS ID CHILDHOOD; THERAPY; INCEST AB Many men are discovering that they are involved with women who were sexually abused as children. However, male partners of female sexual abuse survivors have thus far received little attention in the literature. As these men increasingly seek treatment with concerns of their own, social workers must become familiar with their emotional experiences and treatment needs. This article outlines the major concerns expressed by 20 male partners of sexual abuse survivors. These concerns included conflicts about expressing needs, frustration with various aspects of their relationships, guilt and shame at having feelings, questions about how to deal with relatives, and sexual issues. The author recommends a treatment approach that combines attention to both the individual's and the couple's concerns and uses insight and the safety of the therapeutic relationship to promote growth. The importance of further outreach to partners of women who were sexually abused as children and the need for increased attention to other partner populations are highlighted. RP CHAUNCEY, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT SOCIAL SERV,DIV AMBULATORY CARE,FRUIT ST,BOSTON,MA 02114, USA. NR 16 TC 11 Z9 11 U1 0 U2 0 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 SN 0037-8046 J9 SOC WORK JI Soc. Work PD NOV PY 1994 VL 39 IS 6 BP 669 EP 676 PG 8 WC Social Work SC Social Work GA PP820 UT WOS:A1994PP82000007 PM 7992136 ER PT J AU KNOEFEL, WT KOLLIAS, N WARSHAW, AL WALDNER, H NISHIOKA, NS RATTNER, DW AF KNOEFEL, WT KOLLIAS, N WARSHAW, AL WALDNER, H NISHIOKA, NS RATTNER, DW TI PANCREATIC MICROCIRCULATORY CHANGES IN EXPERIMENTAL PANCREATITIS OF GRADED SEVERITY IN THE RAT SO SURGERY LA English DT Article ID ORGAN-REFLECTANCE SPECTROPHOTOMETRY; HEMODYNAMICS; THERAPY AB Background. A technique with two complementary methods, intravital microscopy (IVM) and diffuse reflectance spectroscopy (DRS), was developed to analyze pancreatic tissue perfusion. Methods. After initial in vivo and in vitro validation of the techniques, we studied pancreatic microcirculation in models of mild, moderate, and severe pancreatitis. Anesthetized Sprague-Dawley rats were randomly allocated to the three models of to serve as controls. Stable systemic hemodynamic parameters were maintained with normal saline solution infusion. Exocrine capillary perfusion was assessed by IVM; hemoglobin oxygenation and hemoglobin content were measured by DRS. Results. Capillary perfusion in mild pancreatitis initially increased significantly at 30 minutes to 155% +/- 38% of baseline values but returned to baseline within 3 hours. Hemoglobin content and oxygen saturation remained stable. In moderate and severe pancreatitis capillary perfusion significantly decreased versus the control group to 12% +/- 6% and 6% (range, 0% to 14%) of baseline values, respectively, at 6 hours. Oxygen saturation decreased significantly in moderate pancreatitis from 48.5% +/- 2.3% to 41.6% +/- 3.5% (p < 0.05) and in severe pancreatitis from 47.2% +/- 1.5% to 38.9% +/- 0.5% (p < 0.05), whereas hemoglobin content did not change. Conclusions. We conclude that (1) IVM and DRS provide both unique and complementary data on tissue perfusion of the pancreas, (2) that moderate and severe experimental pancreatitis are accompanied by progressive tissue ischemia, and (3) that significant stasis (decreased perfusion) and decreased oxygen saturation occur whereas generalized vasoconstriction (decreased hemoglobin levels) was not found. In contrast, mild experimental pancreatitis was accompanied by initial hyperperfusion and normal oxygen delivery was maintained. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. NR 23 TC 108 Z9 112 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 1994 VL 116 IS 5 BP 904 EP 913 PG 10 WC Surgery SC Surgery GA PQ247 UT WOS:A1994PQ24700012 PM 7940196 ER PT J AU NETLAND, PA MUKAI, S COVINGTON, HI AF NETLAND, PA MUKAI, S COVINGTON, HI TI ELEVATED INTRAOCULAR-PRESSURE SECONDARY TO RHEGMATOGENOUS RETINAL-DETACHMENT SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE GLAUCOMA; PHOTORECEPTOR OUTER SEGMENTS; RETINAL DETACHMENT; SCHWARTZS SYNDROME ID PHOTORECEPTOR OUTER SEGMENTS; OPEN-ANGLE GLAUCOMA; AQUEOUS-HUMOR AB Elevated intraocular pressure secondary to rhegmatogenous retinal detachment was described by Ariah Schwartz in 1972, an entity commonly known as Schwartz's syndrome. Photoreceptor outer segments identified in the aqueous of patients with this syndrome are thought to play a role in the elevation of the intraocular pressure. We present two patients with open angles and elevated intraocular pressure associated with retinal detachment. Retinal reattachment surgery resulted in normalization of the intraocular pressure. Electron microscopic examination of aqueous specimens from our patients demonstrated a predominance of photoreceptor outer segments in varying stages of degeneration. In these specimens, inflammatory cells, fibrin, and pigment granules were rarely observed or were absent. We review the literature regarding the epidemiology, clinical characteristics, and pathogenesis of Schwartz's syndrome. RP NETLAND, PA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 29 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD NOV-DEC PY 1994 VL 39 IS 3 BP 234 EP 240 DI 10.1016/0039-6257(94)90196-1 PG 7 WC Ophthalmology SC Ophthalmology GA PW027 UT WOS:A1994PW02700003 PM 7878522 ER PT J AU CONNOR, MJ NANTHUR, J PUHVEL, SM AF CONNOR, MJ NANTHUR, J PUHVEL, SM TI INFLUENCE OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON TNF-ALPHA-LEVELS IN THE SKIN OF CONGENIC HAIRED AND HAIRLESS MICE SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID LANGERHANS CELLS; ENDOTOXIN; KERATINOCYTES; AH AB It has been proposed that TNF-alpha mediates TCDD-induced toxicity. TCDD induces a chloracne-like response in the skin of hairless HRS/J mice but not in congenic haired animals. Using an ELISA, we measured TNF-alpha levels in the skin of TCDD-treated haired and hairless HRS/J mice to test the hypothesis that TNF-alpha mediates the cutaneous toxicity of TCDD. TNF-(a)lpha levels in the skin of haired mice were at or below minimal detectable levles and were unchanged by TCDD exposure. In contrast, TNF-alpha levels were significantly higher in the skin of hairless mice after exposure. The bulk of the induced TNF-alpha was present in the dermis, although detectable amounts were present in the epidermis. To determine if murine skin cells were producing TNF-alpha in direct response to TCDD, cultures of neonatal epidermak keratinocytes and dermal fibroblasts were treated with varying biologically active doses of TCDD or vehicle (DMSO) or with lipopolysaccharide (LPS) as a positive control. Within 24 hr of exposure to LPS, TNF-alpha levels were increased in the culture media of cells tested. In contrast, TCDD treatment (10(-11) M to 10(-7) M) failed to induce detectable TNF-alpha release from either fibroblasts or keratinocytes over a comparable time frame or when measured for up to 6 days following exposure. The failure of TCDD to stimulate TNF-alpha production by keratinocytes or fibroblasts suggests that the rise in dermal TNF-alpha levels seen in vivo is unlikely to be a primary component of the mechanism of toxicity. We suggest that the source of the dermal TNF-alpha in TCDD-treated hairless mouse skin is probably component cells of the inflammatory response. (C) 1994 Academic Press, Inc. C1 W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,VET ADM,LOS ANGELES,CA 90073. RP CONNOR, MJ (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV DERMATOL,LOS ANGELES,CA 90024, USA. FU NIEHS NIH HHS [ES 03597] NR 20 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV PY 1994 VL 129 IS 1 BP 12 EP 15 DI 10.1006/taap.1994.1223 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA PQ822 UT WOS:A1994PQ82200002 PM 7974484 ER PT J AU BARRY, MJ AF BARRY, MJ TI BENIGN PROSTATIC HYPERPLASIA - EFFECTS ON QUALITY-OF-LIFE AND IMPACT ON TREATMENT DECISIONS - COMMENT SO UROLOGY LA English DT Note RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,MED PRACTICES EVALUAT CTR,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD NOV PY 1994 VL 44 IS 5 BP 636 EP 636 DI 10.1016/S0090-4295(94)80195-9 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA PQ847 UT WOS:A1994PQ84700002 ER PT J AU LUYAO, GL BARRY, MJ CHANG, CH WASSON, JH WENNBERG, JE AF LUYAO, GL BARRY, MJ CHANG, CH WASSON, JH WENNBERG, JE TI TRANSURETHRAL RESECTION OF THE PROSTATE AMONG MEDICARE BENEFICIARIES IN THE UNITED-STATES - TIME TRENDS AND OUTCOMES SO UROLOGY LA English DT Article ID REOPERATION FOLLOWING PROSTATECTOMY; MORTALITY; HYPERPLASIA; POPULATION AB Objectives. The purpose of this study was to examine the epidemiology of transurethral resection of the prostate (TURP) and associated risks among Medicare beneficiaries during the period of 1984 to 1990. Methods. Medicare hospital claims for a 20% national sample of Medicare beneficiaries were used to identify TURPs performed during the study period. All reported rates were adjusted to the composition of the 1990 Medicare population. Risks of mortality and reoperation were evaluated using life-table methods. Results. The age-adjusted rate of TURF reached a peak in 1987 and declined thereafter. Similar trends were observed for all age groups. In 1990, the rates of TURF (including all indications) were approximately 25, 19, and 13 per 1000 for men over the age of 75, 70 to 74, and 65 to 69, respectively. The 30-day mortality following TURF for the treatment of benign prostatic hyperplasia (BPH) decreased from 1.20% in 1984 to 0.77% in 1990 (linear trend, p = 0.0001). The cumulative incidence of a second TURF among men with BPH has likewise decreased steadily over time; in this study, the average was 7.2% over 7 years (5.5% when the indication for the second TURF was restricted to BPH only). Conclusions. The rate of TURF has been declining since 1987, conceivably due to increasing availability of alternative treatments or changes in treatment preferences of patients and physicians. Over the same period, the outcomes following TURPs have improved, perhaps due to improved surgical care and changes in patient selection. C1 MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114. RP LUYAO, GL (reprint author), DARTMOUTH COLL,SCH MED,CTR EVALUAT CLIN SCI,DEPT FAMILY & COMMUNITY MED,HANOVER,NH 03755, USA. FU AHRQ HHS [HS 06336] NR 19 TC 77 Z9 79 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0090-4295 J9 UROLOGY JI UROLOGY PD NOV PY 1994 VL 44 IS 5 BP 692 EP 698 DI 10.1016/S0090-4295(94)80208-4 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA PQ847 UT WOS:A1994PQ84700015 PM 7526526 ER PT J AU TORCHILIN, VP TRUBETSKOY, VS AF TORCHILIN, VP TRUBETSKOY, VS TI POLYMERS ON THE SURFACE OF NANOCARRIERS - MODULATION OF CARRIER PROPERTIES AND BIODISTRIBUTION SO VYSOKOMOLEKULYARNYE SOEDINENIYA SERIYA A & SERIYA B LA Russian DT Article ID CIRCULATION TIME; POLYETHYLENE-GLYCOL; LIPOSOMES; STABILITY; MEMBRANES; PROTEINS; VESICLES; PROLONG; BINDING; SYSTEM AB Physico-chemical and biological properties (including biodistribution) of nanoparticulate drug carriers (polymeric nanoparticles, liposomes, latex particles, micelles, etc.) can be modified in a desirable fashion by grafting various polymers to the carrier surface. The most vivid example of such modification is the preparation of longcirculating liposomes by coating them with polyethylene glycol (PEG). The mechanism of PEG protective action is described in terms of polymer properties in solution. It includes the formation of impermeable ''conformational cloud'' of PEG over the liposome surface, which prevents liposome interaction with other substances from the surrounding medium. Fluorescence quenching experiments as well as computer simulation confirm the importance of polymer chain flexibility for steric protection effect. Flexible synthetic polymers other than PEG (such as polyacrylamide or polyvinylpyrrolidone) can also serve as steric protectors for nanocarriers. The optimization of carrier (liposome) modification in respect of polymer-to-carrier ratio permits to find conditions where some other functional moieties might be grafted onto carrier surface together with protecting polymer. Using this approach sterically protected long-circulating immunotargeted carriers (liposomes) have been prepared, which demonstrated good combination of longevity and targetability in vivo. Surface coating with PEG was also proved to be effective in steric stabilization of polymeric biodegradable nano-carriers for drugs and diagnostic agents, as well as for nondegradable latex particles. Surface grafting of nanocarriers with certain polymers can influence their spectral properties. Thus, the contrast properties of Gd-containing liposomes used for experimental MR imaging (for example, lymph nodes imaging) might be improved by simultaneous incorporation of Gd-containing chelate and PEG into the liposomal membrane. Generally speaking, surface modification with different polymers is a powerful tool for designing nanocarriers with desired properties. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP TORCHILIN, VP (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02129, USA. NR 38 TC 3 Z9 3 U1 2 U2 3 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0507-5475 J9 VYSOKOMOL SOEDIN JI Vysokomol. Soedin. PD NOV PY 1994 VL 36 IS 11 BP 1880 EP 1893 PG 14 WC Polymer Science SC Polymer Science GA PX969 UT WOS:A1994PX96900011 ER PT J AU YAMAMOTO, M SCHWARTING, GA CRANDALL, JE AF YAMAMOTO, M SCHWARTING, GA CRANDALL, JE TI ALTERED 9-O ACETYLATION OF DISIALOGANGLIOSIDES IN CEREBELLAR PURKINJE-CELLS OF THE NERVOUS MUTANT MOUSE SO BRAIN RESEARCH LA English DT Article DE GANGLIOSIDE; PURKINJE CELL; CEREBELLUM; MUTANT MOUSE; GLYCOLIPID; ELECTRON MICROSCOPY; MONOCLONAL ANTIBODY ID MONOCLONAL-ANTIBODIES; CORTEX; LOCALIZATION; BRAIN; COMPARTMENTS; GANGLIOSIDE; ANTIGENS; NEURONS AB Some gangliosides in the nervous system are developmentally down-regulated, but many other gangliosides continue to be expressed in the adult nervous system. We have previously demonstrated that the 9-O-acetylated gangliosides recognized by a monoclonal antibody, P-path, confer unique compartmentation among Purkinje cell groups in the normal adult cerebellum. We have continued to explore the role of this group of gangliosides in cerebellar organization by investigating the biochemical and cellular expression of this unique epitope in the cerebellum of the mutant mouse, nervous, where postnatally, most Purkinje cells degenerate. Overall ganglioside composition of nervous cerebellum is similar to wild type cerebellum. However, quantitative analysis of gangliosides by TLC-immunostaining shows that the relative concentration of 9-O-acetylated gangliosides varies considerably. In nervous cerebellum, there is more than a three-fold increase in the concentration of 9-O-acetyl disialolactosyl ceramide (GD3), and 9-O-acetyl disialolactoneotetraosyl ceramide (LD1) is decreased to 25% of wild type. In addition, GD3 ganglioside, the immediate precursor of 9-O-acetyl GD3, is detected at 1/3 of the level of wild type cerebellum, and LD1 ganglioside, the precursor of 9-O-acetyl LD1, is virtually absent from nervous cerebellum. Thus, in nervous cerebellum the ratio of 9-O-acetyl GD3 to its disialoganglioside precursor is dramatically increased compared to wild type cerebellum In accord with the altered expression of 9-O-acetyl gangliosides, immunoelectron microscopy demonstrates a change in the subcellular distribution in mutant Purkinje cells. Instead of being associated with the somatic and dendritic membranes, P-path immunoreactivity is located internally, in the cytoplasm of Purkinje cell bodies and their dendrites. In addition to the changes in the cerebellum, the other regions of the brain decreased in size by about 15% in the nervous mutant. In the ganglioside composition of these regions of nervous brain, 9-O-acetyl GD3 nearly doubled, but 9-O-acetyl LD1 and other gangliosides did not differ. Our findings of significant changes in 9-0-acetylated gangliosides, accompanied by the overall decrease in brain size, suggest that carbohydrate or glycolipid metabolism is abnormal in the nervous mutant mouse brain. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,WALTHAM,MA 02254. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NICHD NIH HHS [HD05515]; NINDS NIH HHS [NS24386] NR 26 TC 8 Z9 8 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 OCT 31 PY 1994 VL 662 IS 1-2 BP 223 EP 232 DI 10.1016/0006-8993(94)90816-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PP066 UT WOS:A1994PP06600027 PM 7859075 ER PT J AU BOOTH, RG BALDESSARINI, RJ MARSH, E OWENS, CE AF BOOTH, RG BALDESSARINI, RJ MARSH, E OWENS, CE TI ACTIONS OF (+/-)-7-HYDROXY-N,N-DIPROPYLAMINOTETRALIN (7-OH-DPAT) ON DOPAMINE SYNTHESIS IN LIMBIC AND EXTRAPYRAMIDAL REGIONS OF RAT-BRAIN SO BRAIN RESEARCH LA English DT Note DE AMINOTETRALIN; AUTORECEPTOR; D-2; D-3; DOPAMINE; 7-OH-DPAT; (+/-)-7-HYDROXY-N,N-DIPROPYLAMINOTETRALIN; RECEPTOR; TYROSINE HYDROXYLASE ID MOLECULAR-CLONING; RECEPTOR; EXPRESSION; D1; GENE; D2; D3; LOCALIZATION; ACTIVATION; RNA AB The proposed D-3-selective ligand (+/-)-7-hydroxy-N,N-dipropylaminotetralin (7-OH-DPAT) inhibited tyrosine hydroxylase in vitro (IC50 = 0.6-0.7 mu M) and dihydroxyphenylalanine (DOPA) accumulation in vivo (ID50 = 4.8-6.4 mg/kg) in two autoreceptor models in extrapyramidal and limbic tissue in rat forebrain, without consistent regional selectivity. Some limbic selectivity (ID50 = 10 vs. 29 mg/kg) was found in an in vivo model permitting expression of postsynaptic D-3 and D-2 receptor activity. The effects were partially blocked by S(-)-eticlopride alone, and fury after reserpine pretreatment. The results suggest that 7-OH-DPAT activates D-3 or D-2 autoreceptors, alters dopamine storage or release, and may interact with some limbic selectivity at postsynaptic D-3 and D-2 receptors as a partial agonist. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BELMONT,MA 02178. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,MAILMAN RES CTR,MCLEAN DIV,BELMONT,MA 02178. RP BOOTH, RG (reprint author), UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,CHAPEL HILL,NC 27599, USA. FU NIMH NIH HHS [MH-278-90-007, MH-34006, MH-47370] NR 27 TC 23 Z9 23 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 OCT 31 PY 1994 VL 662 IS 1-2 BP 283 EP 288 DI 10.1016/0006-8993(94)90827-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PP066 UT WOS:A1994PP06600038 PM 7859086 ER PT J AU BIANCHI, S FABIANI, S MURATORI, M ARNOLD, A SAKAGUCHI, K MIKI, T BRANDI, ML AF BIANCHI, S FABIANI, S MURATORI, M ARNOLD, A SAKAGUCHI, K MIKI, T BRANDI, ML TI CALCIUM MODULATES THE CYCLIN D1 EXPRESSION IN A RAT PARATHYROID CELL-LINE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RETINOBLASTOMA PROTEIN; GENE-EXPRESSION; G1; PHASE; FIBROBLASTS; CLONING; KINASE; G(1); ACTIVATION; INHIBITION AB We have used a rat epithelial parathyroid cell line (PT-r) to study the expression and regulation of D-type cyclins, In PT-r cells the cyclin D1 gene is the most abundantly expressed, being transcribed in at least two mRNAs whose levels oscillate during the cell cycle. We also screened a cDNA library prepared from PT-r cells with the human cyclin D1 probe and isolated its rat homologue. Cyclin D2 and D3 mRNAs are both represented in PT-r cells but the former one is only barely detectable. Moreover, the oscillation of cyclin D3 transcript is slightly delayed when compared to cyclin D1 and D2. Since extracellular calcium inhibits parathyroid cell proliferation, we looked for the effect of the ion on the expression of cyclin D genes in PT-r cells. Increasing amounts of calcium in the incubation medium reduced the expression of rat cyclin D1 and D2. The effect appears to be cell-specific and probably mediated through the inhibition of mitogenic signalling pathways. (C) 1994 Academic Press, Inc. C1 UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,ENDOCRINE UNIT,I-50139 FLORENCE,ITALY. MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA55909]; NIDDK NIH HHS [DK11794] NR 34 TC 23 Z9 24 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 28 PY 1994 VL 204 IS 2 BP 691 EP 700 DI 10.1006/bbrc.1994.2515 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PN634 UT WOS:A1994PN63400037 PM 7980531 ER PT J AU BUSH, AI PETTINGELL, WH DEPARADIS, M TANZI, RE WASCO, W AF BUSH, AI PETTINGELL, WH DEPARADIS, M TANZI, RE WASCO, W TI THE AMYLOID BETA-PROTEIN PRECURSOR AND ITS MAMMALIAN HOMOLOGS - EVIDENCE FOR A ZINC-MODULATED HEPARIN-BINDING SUPERFAMILY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ALZHEIMERS-DISEASE; HUMAN PLATELETS; PURIFICATION; CDNA; GENE; EXPRESSION AB The Alzheimer beta-amyloid precursor protein (APP) contains an ectodomain zinc binding site that has been reported to modulate the heparin affinity and protease-inhibitory properties of the molecule. This motif, GVEFVCCP, is highly conserved in amyloid precursor-like proteins 1 and 2 (APLP1 and APLP2), as well as in the Drosophila and Caenorhabditis elegans APP-like proteins (APPL and APL-1). To determine whether the function of this domain is preserved in the human APP-like proteins, the effect of zinc in modulating the elution profile of these proteins upon heparin-Sepharose chromatography was studied. Both APLP1 and APLP2 bound heparin-Sepharose and had NaCl elution profiles similar to that of APP. As previously reported for APP, zinc increased the recovery of APLP1 and APLP2 upon heparin-Sepharose chromatography. APP, APLP1, and APLP2 all bind zinc-chelating Sepharose, indicating that the zinc binding motif may be functionally conserved in these proteins. Additionally, APP, APLP1, and APLP2 migrate at higher molecular sizes (approximate to 40 kDa) on SDS-polyacrylamide gel electrophoresis than their predicted molecular sizes. We report data that compare the physicochemical properties of APP to its novel APLP homologues and indicate that these molecules behave as a family of zinc-modulated, heparin-binding proteins. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GENET & AGING LAB,BOSTON,MA 02129. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [R01 AG11899-01]; NINDS NIH HHS [R01 NS30428-03] NR 31 TC 92 Z9 95 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 28 PY 1994 VL 269 IS 43 BP 26618 EP 26621 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ931 UT WOS:A1994PQ93100008 PM 7929392 ER PT J AU CASTELEIN, H GULICK, T DECLERCQ, PE MANNAERTS, GP MOORE, DD BAES, MI AF CASTELEIN, H GULICK, T DECLERCQ, PE MANNAERTS, GP MOORE, DD BAES, MI TI THE PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR REGULATES MALIC ENZYME GENE-EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOID-X-RECEPTOR; BETA-OXIDATION PATHWAY; A-I GENE; THYROID-HORMONE; RESPONSE ELEMENT; FATTY-ACIDS; CLOFIBRIC ACID; RXR-ALPHA; SUPERFAMILY; RAT AB A new regulatory element for peroxisome proliferator activated receptor (PPAR)/retinoid X receptor (RXR) heterodimers was found in the promoter of the melic enzyme gene. Similar to previously characterized peroxisome proliferator response elements (PPREs), it consists of a direct repeat of sequences related to the half-site consensus AGGTCA with an interspacing of 1 base pair. Specific binding of PPAR/RXR heterodimers to this element was demonstrated. Furthermore, this sequence conferred ciprofibrate responsiveness of a reporter through the homologous malic enzyme or heterologous thymidine kinase promoters. This PPRE presumably mediates the transcriptional effects of peroxisome proliferators on malic enzyme expression. The presence of a PPRE in the promoter of this lipogenic enzyme suggests a broader function for the PPAR in the regulation of lipid metabolism. C1 CATHOLIC UNIV LEUVEN,FAC PHARMACEUT SCI,CLIN CHEM LAB,B-3000 LOUVAIN,BELGIUM. CATHOLIC UNIV LEUVEN,FAC MED,PHARMACOL LAB,B-3000 LOUVAIN,BELGIUM. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. NR 39 TC 138 Z9 140 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 28 PY 1994 VL 269 IS 43 BP 26754 EP 26758 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ931 UT WOS:A1994PQ93100029 PM 7929410 ER PT J AU BRY, L FALK, P HUTTNER, K OUELLETTE, A MIDTVEDT, T GORDON, JI AF BRY, L FALK, P HUTTNER, K OUELLETTE, A MIDTVEDT, T GORDON, JI TI PANETH CELL-DIFFERENTIATION IN THE DEVELOPING INTESTINE OF NORMAL AND TRANSGENIC MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOUSE SMALL-INTESTINE; EXPRESSION; EPITHELIUM; CRYPT; GENE; PATTERNS; KINETICS; RENEWAL; PROTEIN AB Paneth cells represent one of the four major epithelial lineages in the mouse small intestine. It is the only lineage that migrates downward from the stem-cell zone located in the lower portion of the crypt of Lieberkuhn to the crypt base. Mature Paneth cells release growth factors, digestive enzymes, and antimicrobial peptides from their apical secretory granules. Some of these factors may affect the crypt stem cell, its transit-cell descendants, differentiating villus-associated epithelial lineages, and/or the gut microflora. We used single and multilabel immunocytochemical methods to study Paneth cell differentiation during and after completion of gut morphogenesis in normal, gnotobiotic, and transgenic mice as well as in intestinal isografts. This lineage emerges coincident with cytodifferentiation of the fetal small intestinal endoderm, formation of crypts from an intervillus epithelium, and establishment of a stem-cell hierarchy. The initial differentiation program involves sequential expression of cryptdins, a phospholipase A(2) (enhancing factor), and lysozyme. A dramatic increase in Paneth cell number per crypt occurs during postnatal days 14-28, when crypts proliferate by fission. Accumulation of fucosylated and sialylated glycoconjugates during this period represents the final evolution of the lineage's differentiation program. Establishment of this lineage is not dependent upon instructive interactions from the microflora. Transgenic mice containing nucleotides -6500 to +34 of the Paneth cell-specific mouse cryptdin 2 gene linked to the human growth hormone gene beginning at its nucleotide +3 inappropriately express human growth hormone in a large population of proliferating and nonproliferating cells in the intervillus epithelium up to postnatal day 5. Transgene expression subsequently becomes restricted to the Paneth cell lineage in the developing crypt. Cryptdin 2 nucleotides -6500 to +34 should be a useful marker of crypt morphogenesis and a valuable toot for conducting gain of-function or loss-of function experiments in Paneth cells. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. KAROLINSKA INST,MED MICROBIAL ECOL LAB,S-17177 STOCKHOLM,SWEDEN. RP BRY, L (reprint author), WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL,ST LOUIS,MO 63110, USA. FU NIDDK NIH HHS [DK37960, DK44632] NR 24 TC 157 Z9 165 U1 0 U2 8 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 OCT 25 PY 1994 VL 91 IS 22 BP 10335 EP 10339 DI 10.1073/pnas.91.22.10335 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800020 PM 7937951 ER PT J AU AOKI, Y ISSELBACHER, KJ PILLAI, S AF AOKI, Y ISSELBACHER, KJ PILLAI, S TI BRUTON TYROSINE KINASE IS TYROSINE-PHOSPHORYLATED AND ACTIVATED IN PRE-B LYMPHOCYTES AND RECEPTOR-LIGATED B-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE X CHROMOSOME LINKED AGAMMAGLOBULINEMIA; PRE-ANTIGEN RECEPTOR; B-CELL SIGNALING ID X-LINKED AGAMMAGLOBULINEMIA; ANTIGEN RECEPTOR; LIGHT CHAIN; SRC FAMILY; BETA-CHAIN; XID MICE; IMMUNOGLOBULIN; GENES; ASSOCIATION; EXPRESSION AB The gene encoding Bruton tyrosine kinase (Btk) is known to be mutated in human X chromosome-linked agammaglobulinemia and in the Xid mouse. This kinase was examined in B lymphocytes before and after antigen receptor ligation and also in pre-B cells. Btk was found to be catalytically activated and tyrosine phosphorylated in response to anti-IgM stimulation in B cells. This kinase is also constitutively phosphorylated on tyrosine residues in pre-B cells. These findings point to a functional role for Btk in pre-antigen and antigen receptor signaling during B-cell development and provide a biochemical explanation for the X-linked genetic syndromes already linked to this kinase. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIAID NIH HHS [AI 33507, AI 27835] NR 35 TC 150 Z9 150 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 OCT 25 PY 1994 VL 91 IS 22 BP 10606 EP 10609 DI 10.1073/pnas.91.22.10606 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800076 PM 7524098 ER PT J AU UEDA, T RIEU, P BRAYER, J ARNAOUT, MA AF UEDA, T RIEU, P BRAYER, J ARNAOUT, MA TI IDENTIFICATION OF THE COMPLEMENT IC3B BINDING-SITE IN THE BETA-2 INTEGRIN CR3 (CD11B/CD18) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ADHESION MOLECULES; REPERFUSION INJURY; COMPLEMENT ACTIVATION; INFLAMMATION ID LEUKOCYTE ADHESION MOLECULES; MEMBRANE GLYCOPROTEIN MO1; CELLULAR ADHESION; MAC-1 CD11B/CD18; CD11 CD18; RECEPTORS; PROTEINS; DOMAIN; ORGANIZATION; SUPERFAMILY AB The divalent cation-dependent interaction of the beta 2 integrin CR3 (CD11b/CD18) with the major complement opsonic C3 fragment iC3b is an important component of the central role of CR3 in inflammation and immune clearance. In this investigation we have identified the iC3b binding site in CR3. A recombinant fragment representing the CR3 A domain, a 200-amino acid region in the ectodomain of the CD11b subunit, bound to iC3b directly and in a divalent cation-dependent manner. The iC3b binding site was further localized to a short linear peptide that also bound iC3b directly and inhibited iC3b binding to the A domain as well as to CR3 expressed by human neutrophils. These data establish a major recognition function for the integrin A-domain and have important implications for development of novel antiinflammatory therapeutics. C1 MASSACHUSETTS GEN HOSP,DEPT MED,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIAID NIH HHS [AI-28465]; NIDDK NIH HHS [DK-48549] NR 25 TC 153 Z9 154 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 OCT 25 PY 1994 VL 91 IS 22 BP 10680 EP 10684 DI 10.1073/pnas.91.22.10680 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PP698 UT WOS:A1994PP69800091 PM 7524101 ER PT J AU SIMON, HB AF SIMON, HB TI PATIENT-DIRECTED, NONPRESCRIPTION APPROACHES TO CARDIOVASCULAR-DISEASE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; ACUTE MYOCARDIAL-INFARCTION; LOWER BLOOD-PRESSURE; UNITED-STATES PHYSICIANS; MODERATE ALCOHOL-CONSUMPTION; RANDOMIZED CLINICAL-TRIALS; SUSTAINED-RELEASE NIACIN; VITAMIN-E CONSUMPTION; APOLIPOPROTEIN-A-I AB The control of coronary artery disease requires both physician-directed interventions and patient-directed lifestyle changes that may include nonprescription supplements. All patients should be encouraged to exercise regularly. They should be advised to avoid exposure to tobacco smoke and to strive to attain ideal body weight. Patients should also be encouraged to establish diets that are low in cholesterol and fat and high in dietary fiber. Supplements of water-soluble fiber may be useful for selected patients. Diets rich in antioxidant vitamins should also be stressed. Antioxidant supplements may be warranted in individuals with coronary artery disease or risk factors. Pending further study, patients should be encouraged to consume more fish but not fish oil supplements. Therapeutic doses of niacin should not be used without medical supervision. Chromium and other nutritional supplements, however, may merit consideration in selected cases. Physicians should stress the use of nonpharmacologic means to reduce blood pressure and discuss interventions that could reduce excessive stress. With appropriate screening and precautions, selected individuals should benefit from low-dose aspirin prophylaxis and possibly from low-dose alcohol consumption. Because these patient-directed interventions receive less attention in the scientific literature, they were selected for review herein. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. HARVARD UNIV, SCH MED, CTR CARDIOVASC HLTH, BOSTON, MA USA. RP MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. NR 229 TC 10 Z9 10 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 24 PY 1994 VL 154 IS 20 BP 2283 EP 2296 DI 10.1001/archinte.154.20.2283 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA PN185 UT WOS:A1994PN18500003 PM 7944851 ER PT J AU YOKOTA, M PETERSON, JW TANI, E YAMAURA, I AF YOKOTA, M PETERSON, JW TANI, E YAMAURA, I TI THE IMMUNOHISTOCHEMICAL DISTRIBUTION OF PROTEIN-KINASE-C ISOZYMES IS ALTERED IN THE CANINE BRAIN AND BASILAR ARTERY AFTER SUBARACHNOID HEMORRHAGE SO NEUROSCIENCE LETTERS LA English DT Article DE PROTEIN KINASE C; SUBARACHNOID HEMORRHAGE; IMMUNOHISTOCHEMISTRY; BRAIN; BASILAR ARTERY ID SMOOTH-MUSCLE; GROWTH-FACTOR; CONTRACTION; ACTIVATION AB The effects of subarachnoid hemorrhage on immunoreactivities of protein kinase C isozymes (alpha, beta, gamma) were studied in canine brain and basilar artery. Mild and severe constriction of the basilar artery was shown 2 days and 7 days after hemorrhage, respectively. In control brain tissues, the isozymes showed distinct distributions and following hemorrhage, reactive astrocytes with protein kinase C alpha staining emerged in the surface of the pens and hippocampus. The control basilar artery showed protein kinase C alpha staining and its staining was decreased on day 7, consistent with the result of immunoblot. Our results demonstrated that subarachnoid hemorrhage induces gliosis with heavy protein kinase C alpha staining and down-regulation of protein kinase C in the artery. C1 MASSACHUSETTS GEN HOSP,CEREBROVASC BIOPHYS LAB,BOSTON,MA. RP YOKOTA, M (reprint author), HYOGO MED UNIV,DEPT NEUROSURG,1-1 MUKOGAWA CHO,NISHINOMIYA,HYOGO 663,JAPAN. NR 10 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 24 PY 1994 VL 180 IS 2 BP 171 EP 174 DI 10.1016/0304-3940(94)90514-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA PQ428 UT WOS:A1994PQ42800022 PM 7700574 ER PT J AU POMBO, CM BONVENTRE, JV AVRUCH, J WOODGETT, JR KYRIAKIS, JM FORCE, T AF POMBO, CM BONVENTRE, JV AVRUCH, J WOODGETT, JR KYRIAKIS, JM FORCE, T TI THE STRESS-ACTIVATED PROTEIN-KINASES ARE MAJOR C-JUN AMINO-TERMINAL KINASES ACTIVATED BY ISCHEMIA AND REPERFUSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTOONCOGENE EXPRESSION; CEREBRAL-ISCHEMIA; GENE-EXPRESSION; RENAL ISCHEMIA; GERBIL BRAIN; MAP KINASES; PHOSPHORYLATION; FOS; TRANSCRIPTION; TYROSINE AB The signal transduction pathways that mediate activation of trans acting factors controlling an organ's response to ischemia are unknown. The stress-activated protein kinases (SAPKs), a subfamily of the extracellular signal-regulated kinases (ERKs), phosphorylate c-Jun within the amino-terminal transactivation domain and are activated in response to a variety of cellular stresses. We determined whether SAPKs are activated in response to ischemia, an extreme, albeit common, pathophysiologic stress. Rats underwent 40 min of renal ischemia followed by reperfusion for 0, 5, 20, or 90 min. SAPKs were immunoprecipitated from kidney lysates and kinase activity assayed with recombinant GST-c-Jun(1-135), containing the amino-terminal transactivation domain of c-Jun as substrate. SAPKs were not activated by ischemia alone, but reperfusion for as little as 5 min was associated with a 4.6-fold increase in kinase activity. Kinase activity was increased 7.6-fold at 20 min following reperfusion and remained elevated at 90 min of reperfusion (4.9-fold). In contrast, activity of the related ERR-1 and -2 was increased only 1.3-fold and only at the 5-min reperfusion time point. When SAPKs were immunodepleted from kidney extracts prior to incubation of the extracts with agarose-coupled GST-c-Jun(1-135), it was found that SAPKs accounted for the majority of the amino-terminal c-Jun kinase activity of kidney at 5 min following reperfusion. In Madin-Darby canine kidney epithelial cells, ATP repletion, following ATP depletion induced by chemical anoxia, was associated with a 9-15-fold activation of SAPKs with a similar time course of activation to that seen in the kidney after ischemia and reperfusion. In conclusion, the SAPKs are markedly activated very early after reperfusion of ischemic kidney and following ATP repletion of anoxic cells in culture. We propose that this activation of SAPKs may trigger part of the kidney's early genetic response to ischemia, possibly by enhancing trans acting activity of c-Jun. C1 MASSACHUSETTS GEN HOSP, MED SERV, CARDIAC UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, MED SERV, DIABET UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, MED SERV, RENAL UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. PRINCESS MARGARET HOSP, ONTARIO CANC INST, TORONTO M4X 1K9, ON, CANADA. RI Woodgett, Jim/F-1087-2010; OI Woodgett, Jim/0000-0003-3731-5797; Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [DK01986, DK41513]; NIGMS NIH HHS [GM46577] NR 42 TC 238 Z9 239 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 21 PY 1994 VL 269 IS 42 BP 26546 EP 26551 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ930 UT WOS:A1994PQ93000092 PM 7929379 ER PT J AU HARMON, DC NIELSEN, GP MAYOSMITH, WW AF HARMON, DC NIELSEN, GP MAYOSMITH, WW TI A 55-YEAR-OLD MAN WITH A PARASPINAL MASS AND A HISTORY OF RADIATION TREATMENT OF A TESTICULAR-TUMOR - MYOSITIS-OSSIFICANS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion C1 HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP HARMON, DC (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 36 TC 4 Z9 4 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 20 PY 1994 VL 331 IS 16 BP 1079 EP 1084 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PL560 UT WOS:A1994PL56000009 ER PT J AU WERTHEIM, I MUTO, MG WELCH, WR BELL, DA BERKOWITZ, RS MOK, SC AF WERTHEIM, I MUTO, MG WELCH, WR BELL, DA BERKOWITZ, RS MOK, SC TI P53 GENE MUTATION IN HUMAN BORDERLINE EPITHELIAL OVARIAN-TUMORS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID CANCER; OVEREXPRESSION C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. RP MOK, SC (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT OBSTET,GYNECOL & REPROD BIOL,DIV GYNECOL ONCOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [R01CA63381] NR 14 TC 65 Z9 65 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 19 PY 1994 VL 86 IS 20 BP 1549 EP 1551 DI 10.1093/jnci/86.20.1549 PG 3 WC Oncology SC Oncology GA PL354 UT WOS:A1994PL35400015 PM 7932812 ER PT J AU KOWLURU, A METZ, SA AF KOWLURU, A METZ, SA TI CHARACTERIZATION OF NUCLEOSIDE DIPHOSPHOKINASE ACTIVITY IN HUMAN AND RODENT PANCREATIC BETA-CELLS - EVIDENCE FOR ITS ROLE IN THE FORMATION OF GUANOSINE TRIPHOSPHATE, A PERMISSIVE FACTOR FOR NUTRIENT-INDUCED INSULIN-SECRETION SO BIOCHEMISTRY LA English DT Article ID GTP-BINDING PROTEINS; DIPHOSPHATE KINASE; RAT ISLETS; HISTIDINE-RESIDUES; ADENYLATE-CYCLASE; ACTIVATION; MASTOPARAN; RELEASE; GUANINE; INTACT AB We have recently demonstrated a permissive role for GTP in nutrient-induced insulin secretion. One of the possible loci at which GTP might exert its regulatory effects include one (or more) of the GTP-binding proteins which we have identified in subcellular fractions (including secretory granules) of pancreatic islets. Herein, we characterize nucleoside diphosphokinase (NDP kinase) activity, which catalyzes the transphosphorylation of nucleotide diphosphate (e.g., GDP) to nucleotide triphosphates (e.g., GTP) in insulin-secreting cells. The presence of NPP kinase activity in normal rat and human islets, and pure beta (RIN and HIT) cells, was verified by three distinct approaches: first, its catalytic activity (formation of GTP or GTP gamma S from GDP and ATP or ATP gamma S); secondly, by immunologic detection; and third, by quantitating the phosphoenzyme intermediate of NDP kinase, which is involved in a ping-pong phosphotransfer mechanism. Subcellularly, NDP kinase is predominantly cytosolic (with a tetrameric molecular mass of 85-90 kDa) and requires divalent metal ions and thiols for its activity. UDP, which forms an abortive complex with the enzyme, inhibited its activity in a Concentration-dependent manner (K-i = 2 mM). The phosphorylated intermediate of NDP kinase was differentially sensitive to heat, acidic pH, and a histidine-selective reagent, diethyl pyrocarbonate, suggesting that (one of) the phosphoamino acid(s) may be histidine. These data demonstrate that in beta cells NDP kinase undergoes transient phosphorylation and suggest that this phosphate, in turn, is transferred to GDP. If the GTP which is formed thereby is bound to, or channelled to, relevant GTP-binding proteins, it would facilitate the formation of active form of these proteins. NDP kinase might therefore couple mitochondrial oxidative events to extramitochondrial sites critical to stimulus-secretion coupling. C1 UNIV WISCONSIN, SCH MED, ENDOCRINOL SECT, MADISON, WI 53792 USA. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MADISON, WI 53705 USA. RP UNIV WISCONSIN, SCH MED,CTR CLIN SCI H4568,DEPT MED, DIV ENDOCRINOL, 600 HIGHLAND AVE, MADISON, WI 53792 USA. FU NIDDK NIH HHS [DK37312] NR 57 TC 52 Z9 53 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 18 PY 1994 VL 33 IS 41 BP 12495 EP 12503 DI 10.1021/bi00207a017 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PM582 UT WOS:A1994PM58200017 PM 7918472 ER PT J AU COOKE, HM LYNCH, A AF COOKE, HM LYNCH, A TI BIORHYTHMS AND CHRONOTHERAPY IN CARDIOVASCULAR-DISEASE SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Review DE CARDIOVASCULAR DISEASES; CHRONOPHARMACOLOGY; CIRCADIAN RHYTHM; DOSAGE SCHEDULES ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; TISSUE PLASMINOGEN-ACTIVATOR; CONGESTIVE-HEART-FAILURE; SUDDEN CARDIAC DEATH; PRINZMETALS VARIANT FORM; CHRONIC STABLE ANGINA; CIRCADIAN VARIATION; BLOOD-PRESSURE; DIURNAL-VARIATION AB Recent findings about the effects of biorhythms on cardiovascular disorders are reviewed, and their implications for drug therapy are discussed. The chronobiological approach to physiology evaluates time-dependent changes in biological functions and considers those changes to be multifactorial. Characterization of disease states with this approach allows more accurate determination of the times when patients are at highest risk and therefore in greatest need of preventive measures; it also provides a mechanism for designing optimal drug regimens. There is evidence of circadian variations in the occurrence of myocardial ischemia, acute myocardial infarction, ventricular tachycardia, and sudden cardiac death. Many cardiovascular disorders occur with greatest frequency between 0600 and 1200 in the general population. Blood pressure, too, follows a distinct circadian pattern. Factors affecting circadian variations in cardiovascular disorders include physiological determinants, such as heart rate,catecholamine release, and platelet aggregation-which themselves vary cyclically-and exogenous factors, such as mental stress, anxiety, and physical activity. In chronotherapy, circadian variations in disease states and in the pharmacodynamic properties of drugs are exploited to improve prevention and treatment. Conditions in which research suggests a chronotherapeutic approach may be advantageous include thromboembolism, hypertension, stable exertional angina, variant angina, sustained ventricular tachycardia, and acute myocardial infarction. Information on circadian patterns in the occurrence of many cardiovascular disorders is enabling clinicians to tailor treatment in ways that may lead to improved patient outcomes. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,HARVARD MED NEWS,BOSTON,MA. RP COOKE, HM (reprint author), MASSACHUSETTS COLL PHARM & ALLIED HLTH SCI,DIV PHARM PRACTICE,179 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 122 TC 23 Z9 24 U1 0 U2 3 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD OCT 15 PY 1994 VL 51 IS 20 BP 2569 EP 2580 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PN192 UT WOS:A1994PN19200004 PM 7847420 ER PT J AU HARVEY, EA HAYES, AM HOLMES, LB AF HARVEY, EA HAYES, AM HOLMES, LB TI LESSONS ON OBJECTIVITY IN CLINICAL-STUDIES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Note DE OBJECTIVITY; MEASURING DEVICE; STANDARDIZED LANDMARKS AB Clinical assessments made with measuring devices are generally considered ''objective'' and ''accurate'' and are, therefore, more discriminating than subjective assessments. We show that the choice of measuring devices or non-standardized landmarks to be used with the measuring devices affect the ''accuracy'' of the ''objective'' findings. (C) Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,GENET & TERATOL UNIT,BOSTON,MA 02114. NR 5 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 15 PY 1994 VL 53 IS 1 BP 19 EP 20 DI 10.1002/ajmg.1320530104 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA PK198 UT WOS:A1994PK19800003 PM 7802029 ER PT J AU STEELE, R SCHUNA, AA SCHREIBER, R AF STEELE, R SCHUNA, AA SCHREIBER, R TI CALCIUM-CHANNEL ANTAGONISTS AND GINGIVAL HYPERPLASIA - RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter ID OVERGROWTH; PLAQUE C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,CHICAGO,IL 60612. RP STEELE, R (reprint author), COOK CTY HOSP,CHICAGO,IL 60612, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 15 PY 1994 VL 121 IS 8 BP 625 EP 625 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PL486 UT WOS:A1994PL48600019 ER PT J AU OLOFSSON, AM ARFORS, KE RAMEZANI, L WOLITZKY, BA BUTCHER, EC VONANDRIAN, UH AF OLOFSSON, AM ARFORS, KE RAMEZANI, L WOLITZKY, BA BUTCHER, EC VONANDRIAN, UH TI E-SELECTIN MEDIATES LEUKOCYTE ROLLING IN INTERLEUKIN-1-TREATED RABBIT MESENTERY VENULES SO BLOOD LA English DT Article ID HUMAN-ENDOTHELIAL-CELLS; ANTIHEMOPHILIC FACTOR ANTIGEN; WEIBEL-PALADE BODIES; ADHESION MOLECULE-1; P-SELECTIN; SULFATED POLYSACCHARIDES; VASCULAR ENDOTHELIUM; NEUTROPHIL ADHESION; CHEMOTACTIC FACTORS; ACTIVATION ANTIGEN AB The selectins are lectin-like cell surface glycoproteins that have been implicated in playing a crucial role in the initiation of leukocyte adhesion to endothelial cells (ECs) during inflammation. Binding of selectins under conditions of flow mediates leukocyte rolling, which in vivo is almost exclusively observed in venular microvessels. We have shown in previous experiments that intraperitoneal treatment of rabbits with interleukin-1 beta (IL-1) increases leukocyte rolling in exteriorized mesenteries. In the present study, we used immunohistochemistry of mesenteries and found that IL-1 induced a marked E-selectin immunoreactivity, preferentially in venules. We therefore hypothesized that the increased rolling in response to IL-1 may be related to the induction of E-selectin on venular ECs. Intravital microscopy was used to investigate interactions between leukocytes and ECs after intraperitoneal application of IL-1. The rabbit E-selectin monoclonal antibody (MoAb) 9H9 significantly reduced rolling of leukocytes by approximately 40%. Vehicle atone, class-matched control MoAb or the nonblocking anti-E-selectin MoAb 14G2 had no effect on rolling. These results indicate that leukocytes roll on inflamed venular ECs partly through interactions with E-selectin. Furthermore, we propose that the restricted E-selectin immunoreactivity by venular ECs contributes to the remarkable difference seen between arterioles and venules in exhibiting leukocyte rolling in vivo. (C) 1994 by The American Society of Hematology. C1 EXPTL MED INC,PRINCETON,NJ. LA JOLLA INST EXPTL MED,LA JOLLA,CA 92037. SAN DIEGO REG CANC CTR,SAN DIEGO,CA. HOFFMANN LA ROCHE INC,DEPT INFLAMMAT & AUTOIMMUNE DIS,NUTLEY,NJ 07110. STANFORD UNIV,MED CTR,SCH MED,DEPT PATHOL,IMMUNOL & VASC BIOL LAB,STANFORD,CA 94305. CTR BLOOD RES INC,BOSTON,MA. RI von Andrian, Ulrich/A-5775-2008; Olofsson, Maria /E-8335-2012; Olofsson, Maria/F-6695-2011 OI Olofsson, Maria/0000-0002-7077-7072 FU NHLBI NIH HHS [HL 460 22-02] NR 66 TC 85 Z9 85 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 OCT 15 PY 1994 VL 84 IS 8 BP 2749 EP 2758 PG 10 WC Hematology SC Hematology GA PL359 UT WOS:A1994PL35900041 PM 7522640 ER PT J AU BURN, TC PETROVICK, MS HOHAUS, S ROLLINS, BJ TENEN, DG AF BURN, TC PETROVICK, MS HOHAUS, S ROLLINS, BJ TENEN, DG TI MONOCYTE CHEMOATTRACTANT PROTEIN-1 GENE IS EXPRESSED IN ACTIVATED NEUTROPHILS AND RETINOIC ACID-INDUCED HUMAN MYELOID CELL-LINES SO BLOOD LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; BLOOD MONONUCLEAR LEUKOCYTES; ZINC FINGER GENE; MESSENGER-RNA; GROWTH-FACTOR; RECEPTOR-ALPHA; RAR-ALPHA; POLYMORPHONUCLEAR LEUKOCYTES; DIFFERENTIAL DISPLAY; ENDOTHELIAL-CELLS AB We have used differential display polymerase chain reaction to identify genes that are upregulated after retinoic acid (RA) treatment of human myeloblastic HL-60 cells. Three of the cDNAs cloned hybridized to RA-inducible transcripts on Northern blots, one of which was shown to encode sequences for monocyte chemoattractant protein-1 (MCP-1), a recently described cytokine that is chemotactic for monocytes but not for neutrophils. Nuclear run-on analysis indicated that the upregulation of the MCP-1 gene occurs at the transcriptional level in HL-60 cells. MCP-1 transcript levels also increased after RA treatment of the NB4 acute promyelocytic cell line. MCP-1 transcripts were undetectable in freshly isolated neutrophils by Northern analysis or reverse transcription-polymerase chain reaction but were readily detectable in neutrophils after incubation in media at 37 degrees C for 20 hours, suggesting that an activation event can lead to MCP-1 expression in neutrophils. Immunocytochemistry confirmed the presence of MCP-1 protein in activated neutrophils. This is the first report that the MCP-1 gene is RA-responsive in myeloid cell lines and is expressed in neutrophils. MCP-1 expression by activated neutrophils may play an important role in attracting monocytes to the site of tissue damage or infection. (C) 1994 by The American Society of Hematology. C1 BETH ISRAEL HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,BOSTON,MA. OI HOHAUS, Stefan/0000-0002-5534-7197 FU NCI NIH HHS [CA09161, CA34183] NR 56 TC 71 Z9 72 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 15 PY 1994 VL 84 IS 8 BP 2776 EP 2783 PG 8 WC Hematology SC Hematology GA PL359 UT WOS:A1994PL35900044 PM 7919389 ER PT J AU OCONNELL, JX RENARD, LG LIEBSCH, NJ EFIRD, JT MUNZENRIDER, JE ROSENBERG, AE AF OCONNELL, JX RENARD, LG LIEBSCH, NJ EFIRD, JT MUNZENRIDER, JE ROSENBERG, AE TI BASE OF SKULL CHORDOMA - A CORRELATIVE STUDY OF HISTOLOGIC AND CLINICAL-FEATURES OF 62 CASES SO CANCER LA English DT Article DE CHORDOMA; CHONDROSARCOMA; CHONDROID CHORDOMA; CLIVUS; PATHOLOGY; PROGNOSIS; PROTON BEAM RADIATION THERAPY; RADIATION THERAPY ID RADIATION-THERAPY; CRANIAL CHORDOMAS; TUMORS AB Background. Chordomas are uncommon primary malignant tumors of bone that typically occur in the axial skeleton including the sacrum, vertebrae, and skull base. The base of skull tumors usually are not amenable to complete surgical resection, and most require postoperative radiotherapy. The natural history of skull base chordoma is typified by slow locally invasive tumor progression and eventual death, although few parameters are known that allow stratification of patients into prognostic groups. Methods. Sixty-two patients with skull base chordomas treated at the Massachusetts General Hospital by proton beam irradiation therapy with at least 2 years of follow-up information were reviewed in an attempt to identify clinical and pathologic parameters that predicted outcome. Results. Female sex, tumor necrosis in preradiation treatment biopsy, and tumor volume in excess of 70 ml were each independent predictors of shortened overall survival after radiation therapy for skull base chordoma. Conclusions. Stratification of patients with skull base chordoma into poor and good outcome groups can be performed using the three parameters identified in our study. In addition, the striking difference in survival between the sexes suggests that further investigations of these tumors should include determination of their hormonal receptor status and consideration of hormonal manipulation in their management. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIAT MED,BOSTON,MA 02114. NR 25 TC 104 Z9 108 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1994 VL 74 IS 8 BP 2261 EP 2267 DI 10.1002/1097-0142(19941015)74:8<2261::AID-CNCR2820740809>3.0.CO;2-0 PG 7 WC Oncology SC Oncology GA PL756 UT WOS:A1994PL75600008 PM 7922977 ER PT J AU XU, L SGROI, D STERNER, CJ BEAUCHAMP, RL PINNEY, DM KEEL, S UEKI, K RUTTER, JL BUCKLER, AJ LOUIS, DN GUSELLA, JF RAMESH, V AF XU, L SGROI, D STERNER, CJ BEAUCHAMP, RL PINNEY, DM KEEL, S UEKI, K RUTTER, JL BUCKLER, AJ LOUIS, DN GUSELLA, JF RAMESH, V TI MUTATIONAL ANALYSIS OF CDKN2 (MTS1/P16(INK4)) IN HUMAN BREAST-CARCINOMA SO CANCER RESEARCH LA English DT Note ID CANCER; DELETIONS; 9P AB The CDKN2 gene that encodes the cell cycle regulatory protein cyclin-dependent kinase-4 inhibitor (p16) has recently been mapped to chromosome 9p21. Frequent homozygous deletions of this gene have been documented in cell lines derived from different types of tumors, including breast tumors, suggesting that CDKN2 is a tumor suppressor gene involved in a wide variety of human cancers. To determine the frequency of CDKN2 mutations in breast carcinomas, we screened 37 primary tumors and 5 established breast tumor cell lines by single-strand conformation polymorphism analysis. In addition, Southern blot analysis was performed on a set of five primary breast carcinoma samples and five breast tumor cell lines. Two of the five tumor cell lines revealed a homozygous deletion of the CDKN2 gene, but no mutations were observed in any of the primary breast carcinomas. These results suggest that the mutation of the CDKN2 gene may not be a critical genetic change in the formation of primary breast carcinoma. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NINDS NIH HHS [NS24279] NR 20 TC 160 Z9 172 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 OCT 15 PY 1994 VL 54 IS 20 BP 5262 EP 5264 PG 3 WC Oncology SC Oncology GA PL558 UT WOS:A1994PL55800004 PM 7923151 ER PT J AU MANOME, Y ABE, M HAGEN, MF FINE, HA KUFE, DW AF MANOME, Y ABE, M HAGEN, MF FINE, HA KUFE, DW TI ENHANCER SEQUENCES OF THE DF3 GENE REGULATE EXPRESSION OF THE HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE AND CONFER SENSITIVITY OF HUMAN BREAST-CANCER CELLS TO GANCICLOVIR SO CANCER RESEARCH LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; EPITHELIAL MUCINS; TANDEM REPEATS; LOCUS PUM; CDNA; CLONING; TUMORS; GLYCOPROTEINS; ELEMENTS; CULTURE AB A potentially novel therapeutic strategy for breast cancer treatment involves sensitization of tumor cells to chemotherapy through gene transfer. Clinical application of this approach, however, may be limited by the lack of target cell specificity of currently available gene delivery techniques. Development of vectors with tumor-selective gene expression could overcome this problem. The DF3/MUC1 gene encodes a high molecular weight mucin-like glycoprotein which is overexpressed at the transcriptional level in the majority of human breast cancers. To develop a breast tumor-selective enhancer, we cloned the upstream region of the DF3 gene and have identified a 114-base pair enhancer region that can modulate transcription from heterologous promoters. The present studies demonstrate that the DF3 enhancer sequences can direct selective gene expression in DF3-positive breast carcinoma cells. DF3-positive breast carcinoma cell lines transfected with herpes simplex virus thymidine kinase gene expression cassettes modified by the DF3 enhancer were markedly more sensitive to killing by ganciclovir than were the same cells transfected with the expression cassettes lacking the DF3 enhancer. DF3-negative cell lines transfected with the DF3 enhancer constructs, however, were no more sensitive to ganciclovir than were cells treated with the unmodified expression plasmids. Consistent with an innocent bystander effect, nontransfected human breast carcinoma cells were susceptible in a cell density-dependent manner to ganciclovir-induced cell killing when adjacent to transfected cells. The results also demonstrate that the DF3 enhancer sequences can be effectively incorporated into a retroviral vector to mediate selective gene expression following retroviral infection. These findings suggest that the DF3 promoter/enhancer may be useful for incorporation into vectors designed for gene therapy of breast cancer. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. NR 26 TC 86 Z9 87 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 OCT 15 PY 1994 VL 54 IS 20 BP 5408 EP 5413 PG 6 WC Oncology SC Oncology GA PL558 UT WOS:A1994PL55800027 PM 7923173 ER PT J AU KUROSAWA, K KOBATA, T TACHIBANA, K AGEMATSU, K HIROSE, T SCHLOSSMAN, SF MORIMOTO, C AF KUROSAWA, K KOBATA, T TACHIBANA, K AGEMATSU, K HIROSE, T SCHLOSSMAN, SF MORIMOTO, C TI DIFFERENTIAL REGULATION OF CD27 EXPRESSION ON SUBSETS OF CD4 T-CELLS SO CELLULAR IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TUMOR-NECROSIS-FACTOR; ACTIVATION ANTIGEN CD27; HUMAN LYMPHOCYTES-B; MOLECULAR-CLONING; SURFACE-ANTIGEN; SOLUBLE FORM; BIOLOGICAL CHARACTERIZATION; GENE FAMILY; MEMBER AB Our earlier studies showed that although CD27 was stably expressed on the CD45RA(+)-CD45RO(-)CD29(low) subset of CD4 T cells, its expression on the CD45RA(-)CD45RO(+)CD29(high) subset of CD4 T cells was gradually lost within 3 weeks after PHA activation. In the present study, we further determined the mechanisms by which the CD27 expression was differentially regulated on the subsets of CD4 T cells. We showed that disappearance of CD27 from the surface of the CD45RA(-)CD45RO(+) subset of CD4 T cells was not solely due to the shedding of the CD27 molecule from the cell surface since the release of a soluble form fo the CD27 molecule from the CD45RO(+) CD4 T cells was consistently less than that from CD45RA(+) CD4 T cells. Although the surface CD27 expression was undetectable on long-term cultured T cell lines originally derived from CD45RO(+) CD4 T cells, some of these cells still expressed intracellular CD27 and CD27 mRNA. Moreover, restimulation could not induce CD27 expression on such cells. Further analysis of CD27 protein and mRNA expression at a clonal level showed that cloned cells derived from CD45RO(+) CD4 T cells having lost cell surface expression of CD27 were of two types: one expressed intracellular CD27 mRNA and protein whereas the second lacked both intracellular CD27 mRNA and protein. (C) 1994 Academic Press, Inc. RP KUROSAWA, K (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 40 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 15 PY 1994 VL 158 IS 2 BP 365 EP 375 DI 10.1006/cimm.1994.1283 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PP138 UT WOS:A1994PP13800009 PM 7923389 ER PT J AU MA, J WANG, JH GUO, YJ SY, MS BIGBY, M AF MA, J WANG, JH GUO, YJ SY, MS BIGBY, M TI IN-VIVO TREATMENT WITH ANTI-ICAM-1 AND ANTI-LFA-1 ANTIBODIES INHIBITS CONTACT SENSITIZATION-INDUCED MIGRATION OF EPIDERMAL LANGERHANS CELLS TO REGIONAL LYMPH-NODES SO CELLULAR IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; ANTIGEN-PRESENTING CELLS; MONOCLONAL-ANTIBODY; FLUORESCEIN ISOTHIOCYANATE; IMMUNE-RESPONSES; DENDRITIC CELLS; T-CELLS; INVIVO; HYPERSENSITIVITY; ACTIVATION AB Development of contact hypersensitivity in mice depends on the migration of Langerhans cells from the epidermis to regional lymph nodes. Since ICAM-1 and LFA-1 play important roles in leukocyte migration, we sought to determine whether in vivo administration of anti-ICAM-1 and anti-LFA-1 antibodies would inhibit contact sensitization-induced migration of epidermal Langerhans cells to regional lymph nodes. Twenty-four hours after contact sensitization of mice with FITC, a brightly FITC-stained Ia(+) population of dendritic cells capable of stimulating a FITC specific Ia-restricted T-cell hybridoma was readily detected in their draining lymph nodes. Animals treated with anti-Ia mAb, which depletes Ia(+) cells in lymph nodes and spleen but not Ia(+) Langerhans cells in the epidermis, had normal numbers of FITC-bearing Ia(+) cells capable of stimulating the T-cell hybridoma. Dendritic lymph node cells from mice treated with anti-ICAM-1 and anti-LFA-1 I mAb were devoid of brightly FITC-stained cells and cells capable of stimulating the FITC-specific T-cell hybridoma. The combination of anti-ICAM-1 and anti-LFA-1 mAb completely inhibited the induction of contact hypersensitivity to FITC. Animals treated with anti-ICAM-1 or anti-LFA-1 monoclonal antibodies alone had significantly reduced (by 79 and 36%, respectively) numbers of brightly stained cells capable of stimulating the hybridomas. These data suggest that the adhesion molecules, ICAM-1 and LFA-1, play a significant role in contact hypersensitivity-induced migration of Langerhans cells to regional lymph nodes. The immunomodulatory effects of anti-adhesion molecule antibodies in vivo may be in part due to their effects on antigen-presenting cell migration. (C) 1994 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. CASE WESTERN RESERVE UNIV,SCH MED,INST PATHOL,CLEVELAND,OH 44106. RP MA, J (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02129, USA. NR 36 TC 66 Z9 67 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD OCT 15 PY 1994 VL 158 IS 2 BP 389 EP 399 DI 10.1006/cimm.1994.1285 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PP138 UT WOS:A1994PP13800011 PM 7923390 ER PT J AU PARDO, FS ARONEN, HJ KENNEDY, D MOULTON, G PAIVA, K OKUNIEFF, P SCHMIDT, EV HOCHBERG, FH HARSH, GR FISCHMAN, AJ LINGGOOD, RM ROSEN, BR AF PARDO, FS ARONEN, HJ KENNEDY, D MOULTON, G PAIVA, K OKUNIEFF, P SCHMIDT, EV HOCHBERG, FH HARSH, GR FISCHMAN, AJ LINGGOOD, RM ROSEN, BR TI FUNCTIONAL CEREBRAL IMAGING IN THE EVALUATION AND RADIOTHERAPEUTIC TREATMENT PLANNING OF PATIENTS WITH MALIGNANT GLIOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE FUNCTIONAL IMAGING; POSITRON EMISSION TOMOGRAPHY; ECHO PLANAR MRI; FUNCTIONAL MRI; CEREBRAL BLOOD VOLUME; RADIATION THERAPY TREATMENT PLANNING ID POSITRON EMISSION TOMOGRAPHY; F-18 FLUORODEOXYGLUCOSE; GLUCOSE-UTILIZATION; RECURRENCE; TUMORS; PET AB Purpose: Functional magnetic resonance imaging (MRI) and positron emission tomography are relatively new modalities of great potential value in the evaluation, treatment, and subsequent follow-up care of patients with malignant glioma. We report our experience with the incorporation of functional imaging data into radiation therapy three-dimensional (3-D) treatment planning. Methods and Materials: Over a 24-month period, a total of 37 positron emission tomography and 29 functional MRI studies have been conducted on eight consecutive patients prior to, during, and following the completion of radiation therapy. Functional imaging was conducted prior to radiation therapy treatment planning and at approximate 3-month follow-up time intervals. Results: In two patients, functional imaging provided additional information over conventional imaging modalities and resulted in subsequent modification of conventional radiation therapy treatment planning. Conclusion: Although it is premature to make definitive statements regarding the use of these new imaging parameters in the prognostic setting, functional imaging may likely prove to be a useful adjunct in the initial evaluation, radiation treatment planning, and follow-up care of patients with malignant glioma. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH CANC CTR,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA 02114. RP PARDO, FS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. RI Kennedy, David/H-3627-2012 NR 20 TC 52 Z9 54 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 15 PY 1994 VL 30 IS 3 BP 663 EP 669 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PK604 UT WOS:A1994PK60400017 PM 7928498 ER PT J AU ZIETMAN, AL SHIPLEY, WU AF ZIETMAN, AL SHIPLEY, WU TI ORGAN-SPARING TREATMENT FOR BLADDER-CANCER - TIME TO BEAT THE DRUM SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID RADICAL RADIOTHERAPY; CHEMOTHERAPY; PRESERVATION; COMBINATION; RADIATION; CARCINOMA RP ZIETMAN, AL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,GENITOURINARY ONCOL UNIT,BOSTON,MA 02114, USA. NR 8 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 15 PY 1994 VL 30 IS 3 BP 741 EP 742 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PK604 UT WOS:A1994PK60400030 PM 7928511 ER PT J AU LUO, Y LANING, J HAYASHI, M HANCOCK, PR ROLLINS, B DORF, ME AF LUO, Y LANING, J HAYASHI, M HANCOCK, PR ROLLINS, B DORF, ME TI SEROLOGIC ANALYSIS OF THE MOUSE-BETA CHEMOKINE-JE MONOCYTE CHEMOATTRACTANT PROTEIN-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1; HUMAN ENDOTHELIAL-CELLS; HUMAN MESANGIAL CELLS; PLATELET FACTOR-4; 3-DIMENSIONAL STRUCTURE; CYTOKINE FAMILY; GROWTH-FACTOR; EXPRESSION; GENE; INTERLEUKIN-6 AB Mouse monocyte chemoattractant protein-1 (MCP-1), previously termed JE, is a member of the beta chemokine gene family and a homologue of the human monocyte chemoattractant protein, MCP-1. Mouse rMCP-1 was used to immunize hamsters for the production of mAb. Seven mouse MCP-1-specific mAbs were characterized: two of these mAbs cross-reacted with the human MCP-1, as determined by ELISA. A sensitive and specific capture ELISA for MCP-1 quantitation, which allowed measurement of mouse MCP-1 levels in supernatants from cells stimulated with inflammatory agents, was developed. LPS-stimulated astrocytes produce the highest levels of MCP-1 (80 ng/ml); macrophages and mesangial cells produce lower levels of MCP-1 (2 to 14 ng/ml) after LPS stimulation. IL-1 and TNF-alpha stimulation also can induce low levels of MCP-1 production. Western blot analysis demonstrated that the predominant native form of mouse MCP-1 is a 30-kDa glycoprotein. Two mAbs (2H5 and 6C7) demonstrated dose-dependent neutralization of mouse MCP-1 chemotactic activity. To localize the epitope recognized by one of these neutralizing Abs, the mAb was used to bind a series of genetically engineered truncated variants of human MCP-1. The C-terminal residues 62 to 67 on human MCP-1 molecules seem to be critical to express the epitope recognized by the neutralizing 2H5 anti-MCP-1 mAb. However, multiple sites on the MCP-1 molecule seem to be critical for bioactivity. Thus, these Ab reagents provide a useful tool to explore the biology of the mouse MCP-1 beta chemokine. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA-56057]; NINDS NIH HHS [NS31152] NR 30 TC 40 Z9 42 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 15 PY 1994 VL 153 IS 8 BP 3708 EP 3716 PG 9 WC Immunology SC Immunology GA PM581 UT WOS:A1994PM58100038 PM 7523503 ER PT J AU ARA, G COLEMAN, CN TEICHER, BA AF ARA, G COLEMAN, CN TEICHER, BA TI SR-4233 (TIRAPAZAMINE) ACTS AS AN UNCOUPLER OF OXIDATIVE-PHOSPHORYLATION IN HUMAN MCF-7 BREAST-CARCINOMA CELLS SO CANCER LETTERS LA English DT Article DE SR-4233; TIRAPAZAMINE; HYPOXIC CELL SELECTIVE CYTOTOXINS; MITOCHONDRIAL CYTOTOXINS; BREAST CANCER ID REDUCTIVE BIOACTIVATION; RADIATION-THERAPY; 3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE SR-4233; METABOLIC ACTIVATION; OXYGEN DISTRIBUTION; DTIC NSC-45388; TUMOR HYPOXIA; CYTOTOXIN; TOXIN; PROCARBAZINE AB SR-4233 (Tirapazamine) is a hypoxic cell selective cytotoxic agent currently in Phase I clinical trial. Although SR-4233 is selectively cytotoxic toward hypoxic cells some cytotoxicity toward normally oxygenated cells also occurs. SR-4233 (500 mu M, 1 h) killed about 70% of normally oxygenated and 99% of hypoxic human MCF-7 breast carcinoma cells. Using a polarographic chamber and a Clark O-2 electrode the O-2 consumption of MCF-7 cells was measured in the presence or absence of SR-4233 (500 mu M) or other inhibitors or uncouplers of oxidative phosphorylation. MCF-7 cells exhibited increased O-2 consumption in the presence of SR-4233 alone and after treatment with oligomycin but not after treatment with retenone. The pattern of O-2 consumption observed after treatment with SR-4233 was very similar to that seen when the cells were treated with the classical uncoupler FCCP. After 1 h of exposure to SR-4233 (500 mu M) the cells were not responsive to treatment with oligomycin or FCCP for at least 3 h, but by 24 h post exposure to SR-4233 the cells had regained responsiveness to both FCCP and oligomycin. These results indicate that in normally oxygenated cells SR-4233 acts as an uncoupler of oxidative phosphorylation so that the cells continue to consume O-2 but no ATP is produced. This condition can lead to ATP depletion especially in respiration intensive tissues and may provide an explanation for the muscle cramping observed in some patients treated with SR-4233. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP ARA, G (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU PHS HHS [R01-50174, P01-19589] NR 59 TC 16 Z9 16 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 14 PY 1994 VL 85 IS 2 BP 195 EP 203 DI 10.1016/0304-3835(94)90275-5 PG 9 WC Oncology SC Oncology GA PT739 UT WOS:A1994PT73900009 PM 7954337 ER PT J AU BLUMENTHAL, D AF BLUMENTHAL, D TI THE VARIATION PHENOMENON IN 1994 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP BLUMENTHAL, D (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 12 TC 55 Z9 55 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 13 PY 1994 VL 331 IS 15 BP 1017 EP 1018 DI 10.1056/NEJM199410133311511 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PK504 UT WOS:A1994PK50400011 PM 8084342 ER PT J AU KANG, JX LEAF, A AF KANG, JX LEAF, A TI EFFECTS OF LONG-CHAIN POLYUNSATURATED FATTY-ACIDS ON THE CONTRACTION OF NEONATAL RAT CARDIAC MYOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE OMEGA-6 FATTY ACID; OMEGA-3 FATTY ACID; CARDIOMYOCYTE CONTRACTION; AUTOMATICITY; ANTIARRHYTHMICS ID MODULATION; HEART AB Because of the ability of certain long-chain polyunsaturated fatty acids (PUFAs) to prevent lethal cardiac arrhythmias, we have examined the effects of various long-chain fatty acids on the contraction of spontaneously beating, isolated, neonatal rat cardiac myocytes. The omega 3 PUFA from fish oils, eicosapentaenoic acid [EPA; C20:5 (n - 3)] and docosahexaenoic acid [DHA; C22:6 (n - 3)], at 2-10 mu M profoundly reduced the contraction rate of the cells without a significant change in the amplitude of the contractions. The fatty acid-induced reduction in the beating rate could be readily reversed by cell perfusion with fatty acid-free bovine serum albumin. Addition of either oxygenase inhibitors or antioxidants did not alter the effect of the fatty acids. Arachidonic acid [AA; C20:4 (n - 6)] produced two different effects on the beating rate, an increase or a decrease, or it produced no change. In the case of the increased or unchanged beating rate in the presence of AA, addition of AA oxygenase inhibitors subsequently reduced the contraction rate. The nonmetabolizable AA analog eicosatetraynoic acid (ETYA) always reduced the beating rate, as did EPA or DHA. Two other PUFAs, linoleic acid [C18:2 (n - 6)] and linolenic acid [C18:3 (n - 3)] also exhibited similar but less potent effects compared with EPA or ETYA. In contrast, neither the monounsaturated fatty acid oleic acid [C18:1 (n - 9)] nor the saturated fatty acids stearic acid (C18:0), myristic acid (C14:0), and lauric acid (C12:0) affected the contraction rate. The inhibitory effect of these PUFAs on the contraction rate was similar to that produced by the class I antiarrhythmic drug lidocaine. The fatty acids that are able to reduce the beating rate, particularly EPA and DHA, could effectively prevent and terminate lethal tachyarrhythmias (contracture/fibrillation) induced by high extracellular calcium concentrations or ouabain. These results suggest that free PUFAs can suppress the automaticity of cardiac: contraction and thereby exert their antiarrhythmic effects. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA 02132. FU NIDDK NIH HHS [R01-DK 38165] NR 12 TC 197 Z9 203 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 1994 VL 91 IS 21 BP 9886 EP 9890 DI 10.1073/pnas.91.21.9886 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM138 UT WOS:A1994PM13800046 PM 7937911 ER PT J AU MORIMOTO, C LORD, CI ZHANG, CH DUKECOHAN, JS LETVIN, NL SCHLOSSMAN, SF AF MORIMOTO, C LORD, CI ZHANG, CH DUKECOHAN, JS LETVIN, NL SCHLOSSMAN, SF TI ROLE OF CD26/DIPEPTIDYL PEPTIDASE-IV IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION AND APOPTOSIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD95 ID T-CELL ACTIVATION; MONOCLONAL-ANTIBODY; CD4 CELLS; ANTIGEN; CD26; EXPRESSION; SURFACE; DEATH; INDIVIDUALS; HIV-1 AB To examine the role of CD26/dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) in infection by human immunodeficiency virus type 1 (HIV-1), we utilized CD26 cDNA-transfected Jurkat T-cell lines. Both CD26(-) parental Jurkat cells and mutant CD26(+) (DPPIV-) transfected Jurkat cells were readily infected with HIV-1, whereas wild-type CD26(+) (DPPIV+) transfected Jurkat cells were more resistant to HIV-1 infection. Our results suggest that CD26 is not essential for HIV-1 infectivity as suggested by others but that DPPIV enzyme activity may decrease the efficiency of HIV-1 infection, Of great interest, we found that mutant CD26(+) (DPPIV-) transfectants and CD26(-) parental Jurkat cells strongly expressed CD95 (Fas/Apo-1) and were more sensitive than wild-type CD26(+) (DPPIV+) transfectants to the induction of apoptosis by anti-CD95 monoclonal antibody. These results suggest that CD26 may play a role in HIV-1-associated loss of CD4(+) cells through the process of programmed cell death. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA 02215. RP MORIMOTO, C (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115, USA. RI Duke-Cohan, Jonathan/A-5812-2010 OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NCI NIH HHS [CA55601]; NIAID NIH HHS [AI12069]; NIAMS NIH HHS [AR33713] NR 41 TC 68 Z9 68 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 OCT 11 PY 1994 VL 91 IS 21 BP 9960 EP 9964 DI 10.1073/pnas.91.21.9960 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM138 UT WOS:A1994PM13800061 PM 7937926 ER PT J AU YU, XF MCLANE, MF RATNER, L OBRIEN, W COLLMAN, R ESSEX, M LEE, TH AF YU, XF MCLANE, MF RATNER, L OBRIEN, W COLLMAN, R ESSEX, M LEE, TH TI KILLING OF PRIMARY CD4(+) T-CELLS BY NON-SYNCYTIUM-INDUCING MACROPHAGE-TROPIC HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS; CD4(+) T LYMPHOCYTES ID ENVELOPE PROTEIN; MONONUCLEAR PHAGOCYTES; BIOLOGICAL PHENOTYPE; PRIMARY INFECTION; HTLV-III; HIV-1; AIDS; PROGRESSION; VARIANTS; IDENTIFICATION AB Understanding the mechanism by which human immunodeficiency virus type 1 (HIV-1) kills CD4(+) T lymphocytes is important to the development of therapeutic and prophylactic strategies. Recent studies have indicated that, in some cases, progression to AIDS is associated with the appearance of syncytium-inducing, T cell line-tropic HIV-1 variants. Nevertheless, approximately 50% of subjects with AIDS harbor only non-syncytium-inducing, macrophage-tropic (NSI-M) variants of HIV-1. In most asymptomatic patients, NSI-M HIV-1 isolates are the predominant virus type found. We report here that cytopathicity of NSI-M HIV-1 for primary CD4(+) T lymphocytes can be directly detected in vitro. The extent of CD4(+) T-cell killing was not completely correlated with the rate of viral replication, suggesting that other characteristics of HIV-1 contribute to its cytopathicity. Our findings suggest that: (i) direct killing by NSI-M HIV-1 may contribute to CD4(+) T-lymphocyte depletion in vivo, and (ii) the determinants of HIV-1 cytopathicity for CD4(+) T lymphocytes and cell tropism or syncytia-forming ability are not necessarily tightly linked. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,DEPT MED & MOLEC MICROBIOL,ST LOUIS,MO 63110. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,SCH MED,DEPT MED,DIC INFECT DIS,LOS ANGELES,CA 90073. UNIV PENN,SCH MED,DEPT MED,DIV PULM & CRIT CARE,PHILADELPHIA,PA 19104. NR 29 TC 30 Z9 30 U1 2 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 OCT 11 PY 1994 VL 91 IS 21 BP 10237 EP 10241 DI 10.1073/pnas.91.21.10237 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PM138 UT WOS:A1994PM13800117 PM 7937869 ER PT J AU SIEGLER, EL STINEMAN, MG MAISLIN, G AF SIEGLER, EL STINEMAN, MG MAISLIN, G TI DEVELOPMENT OF COMPLICATIONS DURING REHABILITATION SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CO-MORBIDITY; LENGTH; STAY; PREDICTORS; UNIT AB Background and Methods: Although studies have demonstrated that medical rehabilitation patients have many complications that warrant attention, none has attempted to categorize complications by severity. This retrospective cohort study examined the incidence, types, and severity of problems that interrupt rehabilitation and the major risk factors for these events. Results: Of 1075 patients, 359 (33.4%) had acute medical complications on rehabilitation considered severe enough to interrupt treatment. Of the 359 patients, 158 (44%) required an unexpected transfer off rehabilitation. The most common reasons for unexpected transfer were surgical causes (22.8%), followed by infection or fever (17.1%) and by thromboembolic events (16.5%). Logistic regression revealed that major risk factors for complications requiring transfer were a primary diagnosis of deconditioning or nontraumatic spinal cord injury (adjusted odds ratio, 2.7; confidence interval, 1.8 to 4.2), severity of initial disability (adjusted odds ratio, 1.2; confidence interval, 1.1 to 1.3 for every 10-point drop in a Modified Barthel Index), and number of comorbid conditions (adjusted odds ratio, 1.1; confidence interval, 1.0 to 1.2). Risk factors for any complication were similar, but there was an interaction between comorbidity and the degree of functional impairment; in patients who were severely functionally impaired, the number of comorbidities was not as strongly associated with the risk of complications as it was in patients who were less functionally impaired. Conclusion: There is a complex relationship among the type of underlying medical impairment, severity of functional limitation, comorbidity, and unanticipated medical or surgical complications that interrupt rehabilitation. The interruptions vary both in type and in severity. C1 UNIV PENN,DIV GERIATR MED REHABIL MED & BIOSTAT MED,PHILADELPHIA,PA. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA. OI Siegler, Eugenia/0000-0001-9449-5873 FU NIA NIH HHS [K08-AG00487] NR 12 TC 31 Z9 31 U1 0 U2 0 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 OCT 10 PY 1994 VL 154 IS 19 BP 2185 EP 2190 DI 10.1001/archinte.154.19.2185 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA PK696 UT WOS:A1994PK69600008 PM 7944839 ER PT J AU FRANK, DA GREENBERG, ME AF FRANK, DA GREENBERG, ME TI CREB - A MEDIATOR OF LONG-TERM-MEMORY FROM MOLLUSKS TO MAMMALS SO CELL LA English DT Review ID APLYSIA SENSORY NEURONS; PROTEIN-SYNTHESIS; PHOSPHORYLATED CREB; FACILITATION; SENSITIZATION; TRANSCRIPTION; POTENTIATION; EXPRESSION; INVITRO; MUTANT C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP FRANK, DA (reprint author), CHILDRENS HOSP,DEPT NEUROL,DIV NEUROSCI,BOSTON,MA 02115, USA. NR 30 TC 288 Z9 297 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 7 PY 1994 VL 79 IS 1 BP 5 EP 8 DI 10.1016/0092-8674(94)90394-8 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PK585 UT WOS:A1994PK58500002 PM 7923377 ER PT J AU OLSON, EN ROSENTHAL, N AF OLSON, EN ROSENTHAL, N TI HOMEOBOX GENES AND MUSCLE PATTERNING SO CELL LA English DT Review ID MYOGENIC LINEAGES; DIFFERENTIATION; EXPRESSION; MOUSE; NOTOCHORD; LIMB C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. RP OLSON, EN (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX 77030, USA. NR 22 TC 35 Z9 35 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 7 PY 1994 VL 79 IS 1 BP 9 EP 12 DI 10.1016/0092-8674(94)90395-6 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PK585 UT WOS:A1994PK58500003 PM 7923381 ER PT J AU GEORGOPOULOS, K BIGBY, M WANG, JH MOLNAR, A WU, P WINANDY, S SHARPE, A AF GEORGOPOULOS, K BIGBY, M WANG, JH MOLNAR, A WU, P WINANDY, S SHARPE, A TI THE IKAROS GENE IS REQUIRED FOR THE DEVELOPMENT OF ALL LYMPHOID LINEAGES SO CELL LA English DT Article ID HEMATOPOIETIC STEM-CELLS; NATURAL-KILLER-CELLS; DENDRITIC EPIDERMAL-CELLS; BONE-MARROW; PRECURSOR CELLS; LYMPHOCYTES-T; EXPRESSION; THYMUS; MOUSE; MICE AB The Ikaros gene encodes a family of early hematopoietic- and lymphocyte-restricted transcription factors. Mice homozygous for a germline mutation in the Ikaros DNA-binding domain lack not only T and B lymphocytes and natural killer cells but also their earliest defined progenitors. In contrast, the erythroid and myeloid lineages were intact in these mutant mice. We propose that Ikaros promotes differentiation of pluripotential hematopoietic stem cell(s) into the lymphocyte pathways. In the absence of a functional Ikaros gene, these stem cells are exclusively diverted into the erythroid and myeloid lineages. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV IMMUNOL RES,BOSTON,MA 02114. RP GEORGOPOULOS, K (reprint author), MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129, USA. FU NIAID NIH HHS [R01-AI33062-62]; NIAMS NIH HHS [AR39795-04] NR 36 TC 643 Z9 652 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 7 PY 1994 VL 79 IS 1 BP 143 EP 156 DI 10.1016/0092-8674(94)90407-3 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PK585 UT WOS:A1994PK58500015 PM 7923373 ER PT J AU LAMBERT, C REDMOND, RW AF LAMBERT, C REDMOND, RW TI TRIPLET ENERGY-LEVEL OF BETA-CAROTENE SO CHEMICAL PHYSICS LETTERS LA English DT Article ID SINGLET OXYGEN; ULTRAVIOLET; POLYENES; STATES AB The relaxed energy level of the lowest triplet state (T-1) of beta-carotene has been measured as 19.4 +/- 1.0 kcal mol(-1) using photoacoustic calorimetry. The triplet state of beta-carotene was sensitized using the fullerenes C-60 and C-70. An important consequence of this work is a complete thermodynamic description of the relaxation of T-1 and the conclusion that the beta-carotene triplet is likely to have significantly less than 15.7 kcal mol(-1) available for energy transfer. RP LAMBERT, C (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 15 TC 31 Z9 31 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-2614 J9 CHEM PHYS LETT JI Chem. Phys. Lett. PD OCT 7 PY 1994 VL 228 IS 4-5 BP 495 EP 498 DI 10.1016/0009-2614(94)00942-2 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA PK612 UT WOS:A1994PK61200035 ER PT J AU OKUDA, K ERNST, TJ GRIFFIN, JD AF OKUDA, K ERNST, TJ GRIFFIN, JD TI INHIBITION OF P21(RAS) ACTIVATION BLOCKS PROLIFERATION BUT NOT DIFFERENTIATION OF INTERLEUKIN-3-DEPENDENT MYELOID CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; NERVE GROWTH-FACTOR; TYROSINE KINASE-ACTIVITY; RECEPTOR GENE FAMILY; SIGNAL-TRANSDUCTION; BETA-SUBUNIT; T-CELLS; RAS; PROTEIN; PHOSPHORYLATION AB Interleukin-5 (IL-3) induces proliferation of immature myeloid cells and mast cells and prevents programmed cell death (apoptosis) in vitro. These activities are exerted through binding of IL-3 to specific, high affinity receptors that then initiate a series of intracellular signaling events. Among the earliest of these signaling events in an IL-3-dependent cell line such as 32Dc13 are activation of one or more receptor-associated tyrosine kinases followed by activation of p21(ras). In an effort to define the functional role of p21(ras) activation in mediating the effects of IL-3, we constructed a series of sublines of 32Dc13 in which a dominant inhibitory mutant of Ha-ras (c-Ha-ras(Asn-17)) was expressed under the control of a steroid-inducible promoter. Steroid treatment (dexamethasone, 1 mu M) specifically induced c-Ha-ras(Asn-17) protein and mRNA and blocked IL-3-induced accumulation of p21(ras)-GTP in 32Dc13/p21(ras)N17 cell lines, but not in control cells. Dexamethasone slightly inhibited IL-3-dependent proliferation of control 32Dc13 cell lines (to 80% of maximum), but it completely blocked proliferation of 32Dc13/p21(ras)N17 cell lines and induced cell cycle arrest in G(0)/G(1). This proliferative block could be overcome by cotransfection with v-ras, and was reversible if dexamethasone was washed out. Cells arrested by c-Ha-ras(Asn-17) were viable in culture for >2 weeks, despite their inability to proliferate. Notably, however, these cells remained dependent on IL-3 for viability and initiated apoptosis within 18 h of IL-3 deprivation. Finally, granulocyte colony-stimulating factor-induced differentiation of 32Dc13/p21(ras)N17 cells to neutrophils was not affected by steroid-induced expression of c-Ha-ras(Asn-17) and did not require removal of IL-3. These results suggest that IL-3-induced proliferation and maintenance of cell viability are either initiated through separate signal transduction pathways or require different degrees of p21(ras) activation. Similarly, granulocyte colony-stimulating factor-induced neutrophil differentiation is not blocked by expression of c-Ha-ras(Asn-17). C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. FU NCI NIH HHS [CA34183, CA36167, CA47843] NR 43 TC 46 Z9 46 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 OCT 7 PY 1994 VL 269 IS 40 BP 24602 EP 24607 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000017 PM 7523375 ER PT J AU OGRADY, P KRUEGER, NX STREULI, M SAITO, H AF OGRADY, P KRUEGER, NX STREULI, M SAITO, H TI GENOMIC ORGANIZATION OF THE HUMAN LAR PROTEIN-TYROSINE-PHOSPHATASE GENE AND ALTERNATIVE SPLICING IN THE EXTRACELLULAR FIBRONECTIN TYPE-III DOMAINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKOCYTE COMMON ANTIGEN; IMMUNOGLOBULIN SUPERFAMILY; RNA; EXPRESSION; CLONING; REGION; CONSERVATION; PROMOTER; SYSTEM; USAGE AB The structure of the human leukocyte-common antigen-related molecule (LAR) protein tyrosine phosphatase gene was elucidated using phage and cosmid genomic DNA clones. The LAR gene is composed of 33 exons spanning over 85 kilobase pairs. Exon 2 encodes the signal sequence and the first four amino acids in the mature LAR protein. The three immunoglobulin-like domains are encoded by exons 3-7, and the eight fibronectin type III (Fn-III) domains by exons 8-17. Exons 18-22 encode the juxtamembrane and transmembrane domains, and exons 23-33 encode the two conserved tyrosine phosphatase domains and the entire 3'-untranslated region. Exon 1, which presumably encodes the 5'-untranslated sequence, has not been identified. Reverse transcription-polymerase chain reaction analysis revealed the alternative splicing of a mini exon (exon 13) in the Fn-III domain 5 of human LAR and other related genes (rat LAR, rat PTP sigma, and human PTP delta). RNase protection analysis showed that the human LAR mRNA in which exon 13 is spliced out is the major mRNA species in all cell lines examined. Reverse transcription-polymerase chain reaction analysis revealed further alternative splicing of LAR mRNA involving the Fn-III domains 4, 5, 6, and 7 in various combinations. These findings will facilitate the understanding of the physiological functions of the LAR extracellular domain. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-51132]; NIAID NIH HHS [AI-26598] NR 41 TC 50 Z9 51 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 OCT 7 PY 1994 VL 269 IS 40 BP 25193 EP 25199 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ490 UT WOS:A1994PQ49000099 PM 7929208 ER PT J AU FU, H XIA, K PALLAS, DC CUI, C CONROY, K NARSIMHAN, RP MAMON, H COLLIER, RJ ROBERTS, TM AF FU, H XIA, K PALLAS, DC CUI, C CONROY, K NARSIMHAN, RP MAMON, H COLLIER, RJ ROBERTS, TM TI INTERACTION OF THE PROTEIN-KINASE RAF-1 WITH 14-3-3-PROTEINS SO SCIENCE LA English DT Article ID P21(RAS); REGION; FAMILY; MIDDLE; RAS AB Members of a family of highly conserved proteins, termed 14-3-3 proteins, were found by several experimental approaches to associate with Raf-1, a central component of a key signal transduction pathway. Optimal complex formation required the amino-terminal regulatory domain of Raf-1. The association of 14-3-3 proteins and Raf-1 was not substantially affected by the activation state of Raf. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,SHIPLEY INST MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. OI Collier, R John/0000-0002-2427-4239 FU NCI NIH HHS [CA57327, R01 CA057327]; NIAID NIH HHS [AI22021]; NICHD NIH HHS [HD24926] NR 26 TC 244 Z9 246 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 7 PY 1994 VL 266 IS 5182 BP 126 EP 129 DI 10.1126/science.7939632 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PK582 UT WOS:A1994PK58200040 PM 7939632 ER PT J AU MAYER, RJ DAVIS, RB SCHIFFER, CA BERG, DT POWELL, BL SCHULMAN, P OMURA, GA MOORE, JO MCINTYRE, OR FREI, E AF MAYER, RJ DAVIS, RB SCHIFFER, CA BERG, DT POWELL, BL SCHULMAN, P OMURA, GA MOORE, JO MCINTYRE, OR FREI, E TI INTENSIVE POSTREMISSION CHEMOTHERAPY IN ADULTS WITH ACUTE MYELOID-LEUKEMIA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; HIGH-DOSE CYTARABINE; BONE-MARROW TRANSPLANTATION; ACUTE NONLYMPHOBLASTIC LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; BRITISH COOPERATIVE GROUP; ACUTE MYELOCYTIC-LEUKEMIA; TERM FOLLOW-UP; CONSOLIDATION THERAPY AB Background. About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions. Methods. We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment. Results. Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). in contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups. Conclusions. These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, DIV GEN MED & PRIMARY CARE, BOSTON, MA USA. UNIV MARYLAND, CTR CANC, BALTIMORE, MD 21201 USA. BOWMAN GRAY SCH MED, WINSTON SALEM, NC USA. N SHORE UNIV HOSP, MANHASSET, NY USA. UNIV ALABAMA, BIRMINGHAM, AL USA. DUKE UNIV, MED CTR, DURHAM, NC USA. DARTMOUTH COLL, SCH MED, NORRIS COTTON CANC CTR, LEBANON, NH USA. RP MAYER, RJ (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV MED ONCOL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA33601, CA31983, CA32291] NR 56 TC 944 Z9 967 U1 0 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 6 PY 1994 VL 331 IS 14 BP 896 EP 903 DI 10.1056/NEJM199410063311402 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PJ419 UT WOS:A1994PJ41900002 PM 8078551 ER PT J AU MANKIN, HJ AF MANKIN, HJ TI CHONDROCYTE TRANSPLANTATION - ONE ANSWER TO AN OLD QUESTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID REPAIR RP MANKIN, HJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 12 TC 21 Z9 21 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 6 PY 1994 VL 331 IS 14 BP 940 EP 941 DI 10.1056/NEJM199410063311410 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PJ419 UT WOS:A1994PJ41900010 PM 8078556 ER PT J AU DURE, LS LANDWEHRMEYER, GB GOLDEN, J MCNEIL, SM GE, P AIZAWA, H HUANG, Q AMBROSE, CM DUYAO, MP BIRD, ED DIFIGLIA, M GUSELLA, JF MACDONALD, ME PENNEY, JB YOUNG, AB VONSATTEL, JP AF DURE, LS LANDWEHRMEYER, GB GOLDEN, J MCNEIL, SM GE, P AIZAWA, H HUANG, Q AMBROSE, CM DUYAO, MP BIRD, ED DIFIGLIA, M GUSELLA, JF MACDONALD, ME PENNEY, JB YOUNG, AB VONSATTEL, JP TI IT15 GENE-EXPRESSION IN FETAL HUMAN BRAIN SO BRAIN RESEARCH LA English DT Article DE IT15; HUNTINGTONS DISEASE; IN SITU HYBRIDIZATION; DEVELOPMENT; HUMAN ID TRINUCLEOTIDE CAG REPEAT; HUNTINGTONS-DISEASE GENE; SOMATOSTATIN NEURONS; FUNCTIONAL-ANATOMY; STRIATAL NEURONS; RAT STRIATUM; METHYLAZOXYMETHANOL; LENGTH; INSTABILITY; EXPANSION AB To examine the expression of the gene which causes Huntington's disease (HD), IT15, during development, in situ hybridization of radiolabeled riboprobes was performed in human fetal (gestational ages 20-23 weeks) and adult brain. Optical densities of autoradiographs were determined in various brain regions and compared to cell density in those regions. IT15 expression was found in all regions of the fetal and adult brain, and there was a high degree of correlation of autoradiographic signal with cell number in all regions but germinal matrix in fetal brain and white matter in adult brain. These two regions are notable for their significant proportion of glial cells, and suggest that IT15 expression is predominantly neuronal. There was no preponderance of IT15 expression in striatal compartments in fetal brain as demonstrated by acetylcholinesterase activity, nor was there differential expression of IT15 in brain regions known to be particularly affected in HD. IT15 gene expression is present by 20 weeks gestation in human brain, and at that stage of development exhibits a pattern of distribution which is,similar to adult brain. If a developmentally-regulated role for IT15 exists in the pathogenesis of HD, it must occur prior to 20 weeks gestation. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT PATHOL NEUROBIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MCLEAN HOSP,SCH MED,BRAIN TISSUE RESOURCE CTR,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT NEUROPATHOL,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RI Dure, Leon/B-3243-2008 FU NICHD NIH HHS [HD00983]; NIMH NIH HHS [MH 31862]; NINDS NIH HHS [NS 16367] NR 47 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 3 PY 1994 VL 659 IS 1-2 BP 33 EP 41 DI 10.1016/0006-8993(94)90860-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PJ130 UT WOS:A1994PJ13000005 PM 7820679 ER PT J AU ABRAHAMSSON, SO GELBERMAN, R AF ABRAHAMSSON, SO GELBERMAN, R TI MAINTENANCE OF THE GLIDING SURFACE OF TENDON AUTOGRAFTS IN DOGS SO ACTA ORTHOPAEDICA SCANDINAVICA LA English DT Article ID FLEXOR TENDON AB To determine whether there are differences in the extent to which the superficial cellular layers remain viable and contribute to the healing process, extra- and intrasynovial hindlimb donor tendons of 12 dogs (24 tendons) were labeled with 3H-thymidine in vitro and transferred to the medial and lateral toes of the forepaw. After transplantation, the distribution and amounts of remaining labeled cells within the healing tendon grafts were determined at 1 and 3 weeks after surgery by scintillation countings and autoradiographic examinations. The two types of tendon grafts showed different turnover rates for the elimination of labeled DNA. At 1 week, 25 percent of labeled DNA remained in the extrasynovial grafts and 65 percent in the intrasynovial grafts, The two types of tendon grafts also showed different healing responses histologically. Autradiographic examinations showed that the majority of labeled cells were located in the periphery of the control tendons and that the numbers of labeled cells within the newly proliferated superficial areas of both types of tendon grafts decreased over time. These findings indicate that intrasynovial flexor tendons may possess improved prerequisites for superficial cellular survival and tendon gliding following autogenous tendon grafting. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPED,BOSTON,MA 02114. FU NIAMS NIH HHS [AR 33097] NR 13 TC 7 Z9 8 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6470 J9 ACTA ORTHOP SCAND JI Acta Orthop. Scand. PD OCT PY 1994 VL 65 IS 5 BP 548 EP 552 DI 10.3109/17453679409000912 PG 5 WC Orthopedics SC Orthopedics GA PZ079 UT WOS:A1994PZ07900015 PM 7801761 ER PT J AU NANJI, AA ZHAO, SP SADRZADEH, SMH DANNENBERG, AJ TAHAN, SR WAXMAN, DJ AF NANJI, AA ZHAO, SP SADRZADEH, SMH DANNENBERG, AJ TAHAN, SR WAXMAN, DJ TI MARKEDLY ENHANCED CYTOCHROME-P450 2E1 INDUCTION AND LIPID-PEROXIDATION IS ASSOCIATED WITH SEVERE LIVER-INJURY IN FISH OIL-ETHANOL-FED RATS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Note DE ALCOHOL (ETHANOL); FISH OILS; CYTOCHROME P450; FATTY ACIDS; FREE RADICALS ID DIETARY-FAT; DISEASE; ACID; N-3; PHOSPHOLIPIDS; TISSUES AB We evaluated the role of changes in cytochrome p-450 2E1 (CYP 2E1) and lipid peroxidation in relation to development of severe liver injury in fish oil-ethanol-fed rats. The experimental animals (male Wister rats) were divided into 5 rats/group and were fed the following diets for 1 month: corn oil and ethanol (CO+E) or corn oil and dextrose (CO+D), and fish oil and ethanol (FO+E) or fish oil and dextrose (FO+D). For each animal, microsomal analysis of CYP 2E1 protein, aniline hydroxylase activity, fatty acid composition, and conjugated dienes was conducted. Also, evaluation of severity of pathology was done for each rat. The mean +/- so of the pathology score was significantly higher (p < 0.01) in the FO+E (6.0 +/- 1.3) group than in the CO+E group (3.0 +/- 0.5). No pathological changes were evident in the dextrose-fed controls. The CYP 2E1 protein levels (mean +/- so) were significantly higher (p < 0.01) in the FO+E group (13.1 +/- 2.0) compared with the CO+E (4.7 +/- 1.2) and FO+D (1.8 +/- 0.5) groups. Higher levels of eicosapentaenoic and docosahexaenoic acids and lower levels of arachidonic acid were detected in liver microsomes from rats fed fish oil compared with corn oil. A significant correlation was obtained between CYP 2E1 protein and conjugated diene levels (r = 0.78, p < 0.01). Our results showing markedly increased CYP 2E1 induction and lipid peroxidation in the FO+E group provides one possible explanation for the greater severity of liver injury in this group. C1 DANA FARBER CANC INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. CORNELL UNIV,NEW YORK HOSP,COLL MED,DIV DIGEST DIS,NEW YORK,NY. STRANG CANC PREVENT CTR,NEW YORK,NY. RP NANJI, AA (reprint author), NEW ENGLAND DEACONESS HOSP,DEPT PATHOL,M323,185 PILGRIM RD,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK01992, DK33765] NR 40 TC 181 Z9 185 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1994 VL 18 IS 5 BP 1280 EP 1285 DI 10.1111/j.1530-0277.1994.tb00119.x PG 6 WC Substance Abuse SC Substance Abuse GA PP457 UT WOS:A1994PP45700041 PM 7847620 ER PT J AU GOODMAN, SG LANGER, A DURICA, SS RASKOB, GE COMP, PC GRAY, RJ HALL, JH KELLEY, RP HUA, TA LEE, RJ FUSTER, V AF GOODMAN, SG LANGER, A DURICA, SS RASKOB, GE COMP, PC GRAY, RJ HALL, JH KELLEY, RP HUA, TA LEE, RJ FUSTER, V TI SAFETY AND ANTICOAGULATION EFFECT OF A LOW-DOSE COMBINATION OF WARFARIN AND ASPIRIN IN CLINICALLY STABLE CORONARY-ARTERY DISEASE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SUBSTITUTE HEART-VALVES; MYOCARDIAL-INFARCTION; PLUS DIPYRIDAMOLE; THERAPY; TRIAL; PROPHYLAXIS; REPLACEMENT; PREVENTION; THROMBOSIS; PLACEBO AB The hypothesis that the combination of low-dose aspirin and warfarin therapy is more effective than aspirin alone in secondary prophylaxis after myocardial infarction is to be examined in the Coumadin Aspirin Reinfarction Study. This pilot study addressed the safety and anticoagulation effect of a fixed, low-dose combination in 114 patients (aged 64 +/- 8 years, 85% men) with stable coronary artery disease receiving 3 mg of warfarin plus 80 mg of aspirin daily for 8 weeks. The international normalized ratio (INR) was measured within 72 hours of Initial therapy, and weekly. Of the 110 patients with evaluable INRs, 87 patients (79%) maintained the 3 + 80 mg combination, 19 (17%) had the dose reduced to 1 mg warfarin + 80 mg aspirin, and 4 (4%) discontinued therapy because of a confirmed INR of greater than or equal to 4.5. At steady state, patients had INRs of 1.48 +/- 0.41 (3 + 80 mg group) and 1.21 +/- 0.23 (1 + 80 mg group), and inter- and intra-patient variability (estimated by the mean of the between and within-patient SDs at steady state) was 0.49 +/- 0.08 and 0.13 +/- 0.14, respectively. There was no apparent effect of age on INR distribution. Microscopic hematuria was the most frequent (20%) adverse clinical event, but was unrelated to the INR. Three patients required discontinuation of therapy because of bleeding events (persistent hematuria and epistaxis). A fixed low-dose combination of warfarin and aspirin results in a predictable and stable increase in the INR in a large proportion of patients with coronary artery disease. Provided that early INR testing is undertaken in order to identify patients with significant sensitivity to low-dose warfarin and to establish steady-state C1 UNIV TORONTO,ST MICHAELS HOSP,DEPT MED,DIV CARDIOL,TORONTO M5B 1W8,ON,CANADA. UNIV OKLAHOMA,DEPT MED,OKLAHOMA CITY,OK. UNIV N DAKOTA,SCH MED,GRAND FORKS,ND 58202. MIDWEST HEART ASSOCIATES,INDIANAPOLIS,IN. DUPONT MERCK PHARMACEUT CO,CLIN RES & DEV,WILMINGTON,DE 19880. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 27 TC 22 Z9 23 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 1994 VL 74 IS 7 BP 657 EP 661 DI 10.1016/0002-9149(94)90305-0 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH142 UT WOS:A1994PH14200004 PM 7942522 ER PT J AU HERBERT, V KASDAN, TS AF HERBERT, V KASDAN, TS TI ALFALFA, VITAMIN-E, AND AUTOIMMUNE DISORDERS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID SYSTEMIC LUPUS-ERYTHEMATOSUS; AMINO-ACID; INGESTION C1 BRONX VET AFFAIRS MED CTR,HEMATOL & NUTR RES LABS,BRONX,NY 10468. RP HERBERT, V (reprint author), MT SINAI MED CTR,HEMATOL & NUTR RES LABS,BRONX,NY 10468, USA. NR 11 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1994 VL 60 IS 4 BP 639 EP 640 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PJ930 UT WOS:A1994PJ93000026 PM 8092103 ER PT J AU QUINTANILLAMARTINEZ, L PREFFER, F RUBIN, D FERRY, JA HARRIS, NL AF QUINTANILLAMARTINEZ, L PREFFER, F RUBIN, D FERRY, JA HARRIS, NL TI CD20+ T-CELL LYMPHOMA - NEOPLASTIC TRANSFORMATION OF A NORMAL T-CELL SUBSET SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Note DE B LYMPHOCYTES; CD20+ T CELLS; CD20+BRIGHT; CD20+(DIM); FLOW CYTOMETRY; HEMATOPOETIC NEOPLASMS; LEUKOCYTE ANTIGENS; MALIGNANT LYMPHOMA; T LYMPHOCYTES ID EPSTEIN-BARR-VIRUS; MONOCLONAL-ANTIBODY L26; NON-HODGKINS-LYMPHOMAS; B-CELL; VIRAL-DNA; GENE REARRANGEMENTS; DIAGNOSIS; ANTIGEN; EXPRESSION; PHENOTYPE AB CD20 is a 35-kDa protein that is expressed early in B-cell ontogeny and is lost during terminal B-cell differentiation into plasma cells. It is thought to be B-cell-specific. However, the CD20 antigen, detected by the monoclonal antibody L26, has been reported in some cases of T-cell lymphoma. This report describes a case of a malignant lymphoma coexpressing T-cell-lineage antigens and CD20 and characterization of a CD20+ T-cell population in the peripheral blood of healthy donors. The tumor cells were pleomorphic medium-sized cells that expressed a range of T-cell-specific antigens, including CD2, CD3, CD4, CD5, CD6, CD7, and beta F1. In addition, the tumor cells expressed CD20 on frozen (B1) and paraffin sections (L-26). Stains for other pan-B cell antigens, including CD19 and CD22, and immunoglobulin light and heavy chains were negative. To determine whether this unusual coexpression of T-cell-lineage antigens and CD20 represented aberrant antigen expression or neoplastic transformation of an unusual normal T-cell subset, the authors examined specimens of peripheral blood lymphocytes from healthy donors for evidence of a CD20+ T-cell population by using three-color immunofluorescence analysis by flow cytometry. Two distinct populations of CD20+ cells were observed in peripheral blood. One expressed bright CD20 (6.6% to 23.7%, mean 14.47% of peripheral blood lymphocytes) and other B-cell associated antigens, whereas the other expressed dim CD20 (.94% to 11.90%, mean 3.50% of peripheral blood lymphocytes) and coexpressed CD3. Approximately two thirds (52.8% to 82.3%, mean 64.1%) of the dim CD20 cells were CD8+ and one third (19.2% to 74.1%, mean 37.5) CD4+. These cells also expressed CD5 and the alpha-beta> chain of the T-cell receptor and lacked CD19 and CD22. These results indicate that CD20 is expressed on some normal peripheral blood T cells. CD20 expression by T-cell lymphomas may represent neoplastic transformation of a normal subset of CD20+ T cells rather than aberrant antigen expression by neoplastic cells. The nature of the CD20 antigen on T cells and the function of the normal population remain to be determined. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. INST NACL NUTR,DEPT PATHOL,MEXICO CITY,DF,MEXICO. NR 31 TC 73 Z9 75 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 1994 VL 102 IS 4 BP 483 EP 489 PG 7 WC Pathology SC Pathology GA PL836 UT WOS:A1994PL83600018 PM 7524302 ER PT J AU WONG, TY SUSTER, S AF WONG, TY SUSTER, S TI TRICHOLEMMAL CARCINOMA - A CLINICOPATHOLOGICAL STUDY OF 13 CASES SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE TRICHOLEMMAL CARCINOMA; PILAR NEOPLASMS; SKIN ADNEXAL NEOPLASMS; CLEAR CELL SQUAMOUS CARCINOMA ID CLEAR CELL-CARCINOMA; DESMOPLASTIC TRICHILEMMOMA; SKIN TUMORS; VARIANT AB We describe 13 cases of tricholemmal carcinoma, a rarely recognized cutaneous adnexal neoplasm. The patients were nine men and four women. In general, the tumors presented as slow-growing epidermal papules, indurated plaques, or nodules showing predilection for sun-exposed, hair-bearing skin. The lesions were most frequently misdiagnosed clinically as basal cell carcinoma. Histologically, they showed a variegation of growth patterns including solid, lobular, and trabecular; they were characterized by a proliferation of epithelial cells with features of outer root sheath differentiation, including abundant glycogen-rich, clear cytoplasm, foci of pilar-type keratinization, and peripheral palisading of cells with subnuclear vacuolization. Because of their variable growth pattern, overt cytologic atypia, abundant clear cytoplasm, occasional pagetoid intraepidermal spread, and brisk mitotic activity, these tumors may pose difficulties for diagnosis and be confused with other malignant skin tumors with clear cell changes. Despite the seemingly malignant cytological appearance of these lesions, clinical follow-up in 10 cases showed no recurrence or metastasis over a period of 2-8 years. Thus, conservative surgical excision with clear margins appears to be the treatment of choice for these neoplasms. C1 MT SINAI MED CTR,DEPT PATHOL,4300 ALTON RD,MIAMI BEACH,FL 33140. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV DERMATOPATHOL,BOSTON,MA 02114. MT SINAI MED CTR,ARKADI M RYWLIN DEPT PATHOL & LAB MED,MIAMI BEACH,FL 33140. UNIV MIAMI,SCH MED,MIAMI,FL 33152. NR 27 TC 44 Z9 49 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD OCT PY 1994 VL 16 IS 5 BP 463 EP 473 DI 10.1097/00000372-199410000-00001 PG 11 WC Dermatology SC Dermatology GA PL216 UT WOS:A1994PL21600001 PM 7528473 ER PT J AU ADAMIS, AP MILLER, JW BERNAL, MT DAMICO, DJ FOLKMAN, J YEO, TK YEO, KT AF ADAMIS, AP MILLER, JW BERNAL, MT DAMICO, DJ FOLKMAN, J YEO, TK YEO, KT TI INCREASED VASCULAR ENDOTHELIAL GROWTH-FACTOR LEVELS IN THE VITREOUS OF EYES WITH PROLIFERATIVE DIABETIC-RETINOPATHY SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PERMEABILITY FACTOR; ANGIOGENESIS; TUMOR; MITOGEN; CELLS AB The vitreous levels of the angiogenic polypeptide vascular endothelial growth factor (also known as vascular permeability factor) were measured and compared in eyes with and without proliferative diabetic retinopathy. Undiluted vitreous samples from 20 eyes were collected at the time of vitrectomy, and vascular endothelial growth factor levels were determined by using a time-resolved immunofluorometric assay. Vitreous vascular endothelial growth factor levels were significantly higher in eyes with proliferative diabetic retinopathy than in eyes without proliferative diabetic retinopathy (P = .006; Wilcoxon Rank Sum Test). The median vitreous concentration in the eyes with proliferative diabetic retinopathy was 29.1 pM and exceeded the known concentration required for the maximal proliferation of vascular endothelial cells in vitro. These data are consistent with vascular endothelial growth factor serving as a physiologically relevant angiogenic factor in proliferative diabetic retinopathy. C1 CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. RP ADAMIS, AP (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY00325] NR 25 TC 850 Z9 880 U1 3 U2 21 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 OCT PY 1994 VL 118 IS 4 BP 445 EP 450 PG 6 WC Ophthalmology SC Ophthalmology GA PK509 UT WOS:A1994PK50900004 PM 7943121 ER PT J AU CAJAL, SRY MISSERO, C MARCHETTI, E DOTTO, GP AF CAJAL, SRY MISSERO, C MARCHETTI, E DOTTO, GP TI DERMAL FIBROBLASTS TUMOR SUPPRESSION OF RAS-TRANSFORMED KERATINOCYTES IS ASSOCIATED WITH INDUCTION OF SQUAMOUS-CELL DIFFERENTIATION SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HARVEY SARCOMA-VIRUS; GROWTH-FACTOR-BETA; MOUSE SKIN; H-RAS; HETEROGENEITY; EXPRESSION; MELANOMA; LINES; PROGRESSION; MODULATION AB We have previously reported that tumor formation of ras-transformed keratinocytes can be suppressed by dermal fibroblasts through production of a diffusible growth inhibitory factor of the transforming growth factor-beta (TGF-beta) family. Keratinocytes transformed by ras and E1a oncogenes or papilloma-derived keratinocytes transformed by a ras oncogene show concomitant resistance to dermal fibroblast tumor suppression and TGF-beta growth inhibition We report here that dermal fibroblast tumor suppression is associated with a striking induction of squamous cell differentiation and that this effect is blocked in tumors resistant to dermal fibroblast inhibition. This experimental system strongly supports the notion that suppression of tumorigenicity and induction of a differentiated phenotype are closely associated events. C1 MASSACHUSETTS GEN HOSP E,CBRC DERMATOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP EAST,DEPT DERMATOL,BOSTON,MA. CLIN PUERTA HIERRO,DEPT PATHOL ANAT,MADRID,SPAIN. RI Ramon y Cajal, Santiago/H-4955-2016 OI Ramon y Cajal, Santiago/0000-0002-3867-1390 NR 29 TC 8 Z9 8 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 OCT PY 1994 VL 145 IS 4 BP 846 EP 855 PG 10 WC Pathology SC Pathology GA PL843 UT WOS:A1994PL84300012 ER PT J AU PRINZ, C SCOTT, DR HURWITZ, D HELANDER, HF SACHS, G AF PRINZ, C SCOTT, DR HURWITZ, D HELANDER, HF SACHS, G TI GASTRIN EFFECTS ON ISOLATED RAT ENTEROCHROMAFFIN-LIKE CELLS IN PRIMARY CULTURE SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE CHOLECYSTOKININ B RECEPTOR; HISTAMINE; HISTIDINE DECARBOXYLASE; DEOXYRIBONUCLEIC ACID SYNTHESIS; SIGNAL TRANSDUCTION ID HISTIDINE-DECARBOXYLASE GENE; SELF-REPLICATION RATE; PLASMA GASTRIN; HYPERGASTRINEMIC RATS; TYROSINE KINASES; ENDOCRINE-CELLS; ANTIULCER DRUGS; MUCOSAL CELLS; CHOLECYSTOKININ; STOMACH AB The hormone gastrin stimulates acid secretion by releasing histamine from gastric enterochromaffin-like (ECL) cells and induces ECL cell proliferation in vivo. This study uses a > 90% pure ECL cell preparation in culture to compare gastrin effects on histamine release, histidine decarboxylase (HDC) activity, and DNA synthesis. Gastrin and the cholecystokinin octapeptide (CCK-8, nonsulfated) induced histamine release from ECL cells (24-96 h of primary culture) within 5 min of incubation [concentration eliciting 50% of maximal response (EC(50)), 4 and 2 x 10-(11) M, respectively]. The CCK-B antagonist L-365,260 inhibited this effect [concentration inhibiting 50% of maximal response (IC50), 2 x 10(-8) M], whereas the CCK-A antagonist L-364,718 (10(-8) M) and the tyrosine kinase inhibitor genistein (10(-4) M) had no effect. Histamine release was associated with a biphasic elevation of intracellular Ca2+. Gastrin stimulated HDC activity two- to threefold after 60 min of incubation (EC(50), 10(-10) M). Gastrin also increased DNA synthesis in ECL cells, with an EC(50) of 1.7 x 10(-12) M as measured by the incorporation of 5-bromo-2'deoxyuridine (BrdU). Positive nuclear immunostaining increased two- to threefold in up to 20% of ECL cells after 48-96 h of incubation. This effect was inhibited by L-365,260 (IC50, 5 x 10(-9) M) and by genistein (10(-4) M) but was not altered by L-364,718 (10(-8) M). The antisecretory drugs omeprazole, lansoprazole, and pantoprazole did not affect BrdU incorporation in isolated ECL cells. In conclusion, acute and chronic gastrin effects on the ECL cell are mediated via CCK-B receptors but differ in apparent receptor affinity and signal transduction pathways. C1 UNIV CALIF LOS ANGELES, DEPT PHYSIOL, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, CTR ULCER RES, LOS ANGELES, CA 90073 USA. W LOS ANGELES VET AFFAIRS MED CTR, CTR EDUC GASTROENTER, LOS ANGELES, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-17294, DK-40615] NR 49 TC 125 Z9 125 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 1994 VL 267 IS 4 BP G663 EP G675 PG 13 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA PW598 UT WOS:A1994PW59800023 PM 7524350 ER PT J AU KIUCHI, K SHEN, YT VATNER, SF VATNER, DE AF KIUCHI, K SHEN, YT VATNER, SF VATNER, DE TI MECHANISMS MEDIATING RESPONSIVENESS TO BETA-ADRENERGIC STIMULATION AFTER CORONARY REPERFUSION IN CONSCIOUS DOGS SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE G-PROTEINS; MYOCARDIAL ISCHEMIA; ISOPROTERENOL; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE; BETA-ADRENERGIC RECEPTORS ID ACUTE MYOCARDIAL-ISCHEMIA; ADENYLATE-CYCLASE; INOTROPIC RESPONSES; CALCIUM CHANNELS; PROTEIN-GS; RECEPTOR; SUPERSENSITIVITY; ISOPROTERENOL; INFARCTION; AFFINITY AB The goal of this study was to assess beta-adrenergic receptor (beta-AR) signaling mechanisms in mediating physiological responses to sympathomimetic amines after 45 min coronary artery occlusion followed by 45 min reperfusion. At this time, isoproterenol (Iso) infusion (0.1 mu g.kg(-1). min(-1), n = 5) increased percent wall thickening in previously ischemic subendocardium (Endo) more than in nonischemic Endo (12.6 +/- 1.2 vs. 7.2 +/- 0.6%, P < 0.05), whereas forskolin (25 nmol.kg(-1).min(-1), n = 6) elicited the opposite effect (3.6 +/- 0.6 vs. 10.4 +/- 2.8%, P < 0.05). During Iso and forskolin infusions increases in regional myocardial blood flow in the previously ischemic zone were similar to the nonischemic zone. In all groups, total beta-AR density was depressed in previously ischemic Endo compared with nonischemic Endo (65 +/- 7 vs. 82 +/- 8 fmol/mg, P < 0.05), but the fraction of beta-AR binding agonist with high affinity increased (82 +/- 4 vs. 49 +/- 1%, P < 0.05). The changes in beta-AR were associated with a decrease in Iso-stimulated adenylyl cyclase (22 +/- 8%), a decrease in guanosine 5'-triphosphate (GTP)-stimulatory protein (G(s)) (23 +/- 6%), and a decrease in inhibitory G proteins (16 +/- 4%). However, regional Endo functional responsiveness to beta-AR stimulation was enhanced in reperfused myocardium in response to Iso but not to forskolin. Thus the mechanism of increased number of beta-AR binding agonist with high affinity in previously ischemic myocardium predominated over persistent downregulation of total beta-AR density and reductions in G(s) and adenylyl cyclase activity and correlated best with the physiological response to beta-AR stimulation. These data may also suggest that Iso exerts an action distal to adenylyl cyclase in previously ischemic myocardium. C1 NEW ENGLAND REG PRIMATE RES CTR, SOUTHBOROUGH, MA 01772 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, CHILDRENS SERV, BOSTON, MA 02114 USA. NR 33 TC 17 Z9 17 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 1994 VL 267 IS 4 BP H1578 EP H1588 PG 11 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA PW587 UT WOS:A1994PW58700044 ER PT J AU LEU, AJ BERK, DA YUAN, F JAIN, RK AF LEU, AJ BERK, DA YUAN, F JAIN, RK TI FLOW VELOCITY IN THE SUPERFICIAL LYMPHATIC NETWORK OF THE MOUSE TAIL SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE MICROCIRCULATION; INITIAL LYMPHATICS; FLUORESCENCE MICROLYMPHOGRAPHY; DEXTRAN ID INTERSTITIAL FLUID; VOLUME; CAPILLARIES; MECHANISMS; TRANSPORT; TISSUES; ALBUMIN; PLASMA AB The present study had two goals: 1) to establish an animal model in which a large network of the initial lymphatics of the skin can be investigated in vivo and 2) to measure effective flow velocity (defined as axial component of the flow velocity) in the lymph capillary network of the skin for the first time. A fluorescence microlymphography technique was used to stain the lymph capillaries in the superficial layer of the skin of the nude mouse tail in 10 female animals (mean age 45.8 +/- 2.4 days; mean wt 21.2 +/- 0.8 g). With the use of densitometric image analysis, effective flow velocity along the tail was measured. The network consisted of a honeycomb-like layer of hexagonally shaped meshes that could be stained in all animals. Effective lymph flow velocities were in the range of 1.4-20.4 mu m/s with a mean value of 7.7 +/- 5.9 mu m/s; median value was 6.2 mu m/s (4.5-10.5; 25 and 75% percentiles). This new animal model allows studies of a large network of lymph capillaries in the skin and should provide new insight into the physiology and pathophysiology of the initial lymphatics. C1 MASSACHUSETTS GEN HOSP, DEPT RADIAT ONCOL, EDWIN L STEELE LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RI Yuan, Fan/A-1287-2011; Berk, David/A-4863-2012 OI Berk, David/0000-0002-3855-6886 NR 20 TC 66 Z9 68 U1 0 U2 2 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 OCT PY 1994 VL 267 IS 4 BP H1507 EP H1513 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA PW587 UT WOS:A1994PW58700034 ER PT J AU GRANDALIANO, G CHOUDHURY, GG BISWAS, P ABBOUD, HE AF GRANDALIANO, G CHOUDHURY, GG BISWAS, P ABBOUD, HE TI MITOGENIC SIGNALING OF THROMBIN IN MESANGIAL CELLS - ROLE OF TYROSINE PHOSPHORYLATION SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE GROWTH FACTORS; SIGNAL TRANSDUCTION; GLOMERULUS ID PROTEIN KINASE-C; HUMAN-PLATELETS; RECEPTOR ACTIVATION; PERTUSSIS TOXIN; PATHWAYS; VASOPRESSIN; COAGULATION; ENDOTHELIN; GENISTEIN; INHIBITOR AB Thrombin elicits multiple biological effects on a variety of cells. We have previously shown that thrombin is a potent mitogen for human glomerular mesangial cells. This mitogenic effect of thrombin is associated with activation of phospholipase C (PLC) and induction of platelet-derived growth factor (PDGF) gene expression. The thrombin receptor, which belongs to the guanine nucleotide binding protein (G protein)-coupled receptor family, has recently been shown to induce rapid tyrosine phosphorylation of cellular proteins. In the present study, we investigated the role of protein-tyrosine phosphorylation in mediating the cellular responses elicited by thrombin in human glomerular mesangial cells. Amino acid labeling followed by immunoprecipitation with phosphotyrosine antibodies demonstrate that thrombin stimulates tyrosine phosphorylation of a set of cellular proteins. Treatment of mesangial cells with thrombin followed by immunoblotting with phosphotyrosine antibodies showed three major bands of tyrosine-phosphorylated proteins similar to 130, 70, and 44-42 kDa. Phosphorylation of these proteins was inhibited by two tyrosine kinase inhibitors, herbimycin A and genistein. Both compounds inhibited DNA synthesis and PDGF B-chain gene expression but had no effect on inositol phosphates production or increases in cytosolic calcium in response to thrombin. These data demonstrate that protein-tyrosine phosphorylation is not required for thrombin-induced PLC activation with inositol phosphate formation and subsequent intracellular calcium release, but it is an absolute requirement for thrombin-induced DNA synthesis and PDGF B-chain gene expression. C1 UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV NEPHROL, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET AFFAIRS HOSP, SAN ANTONIO, TX 78284 USA. RI Grandaliano, Giuseppe/G-2963-2012 FU NIDDK NIH HHS [DK-33665, DK-43988] NR 31 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD OCT PY 1994 VL 267 IS 4 BP F528 EP F536 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA PW545 UT WOS:A1994PW54500003 PM 7524356 ER PT J AU HEGARTY, JD BALDESSARINI, RJ TOHEN, M WATERNAUX, C OEPEN, G AF HEGARTY, JD BALDESSARINI, RJ TOHEN, M WATERNAUX, C OEPEN, G TI 100 YEARS OF SCHIZOPHRENIA - A METAANALYSIS OF THE OUTCOME LITERATURE SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DIAGNOSTIC-CRITERIA; AFFECTIVE-DISORDERS; CLINICAL-TRIALS; AMERICAN; CHRONICITY; PROGNOSIS; SYMPTOMS; ILLNESS AB Objective: This study was undertaken to assess the twentieth-century literature on outcome in schizophrenia for historical trends that might be associated with changes in diagnostic and therapeutic practice and to test the hypothesis that both improved biological treatment and changes in diagnostic criteria have influenced outcome. Method: Meta-analysis of the international literature on outcome in schizophrenia or dementia praecox from 1895 to 1992 identified 821 studies; 320 of these, with 51,800 subjects in 368 cohorts, met the inclusion criteria for the study. Results: Only 40.2% of patients were considered improved after follow-ups averaging 5.6 years (range=1-40). Outcome was significantly better when patients were diagnosed according to systems with broad criteria (46.5% were improved) or undefined criteria (41.0% were improved) rather than narrow criteria (27.3% were improved). The proportion of patients who improved increased significantly after mid-century (for 1956-1985 versus 1895-1955, 48.5% versus 35.4%), probably reflecting improved treatment as well as a broadened concept of schizophrenia. However, in the past decade, the average rate of favorable outcome has declined to 36.4%, perhaps reflecting the re-emergence of narrow diagnostic concepts. Conclusions: Overall, less than half of patients diagnosed with schizophrenia have shown substantial clinical improvement after follow-up averaging nearly 6 years, Despite considerable gains in improvement rates after mid-century, there has been a decline since the 1970s. These historical changes probably reflect improved treatment, shifts in diagnostic criteria, and selection bias related to changes in health care. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,PSYCHIAT RES LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BIPOLAR & PSYCHOT DISORDERS PROGRAM,BOSTON,MA 02114. FU NIMH NIH HHS [NIMH MH-31154, NIMH MH-47370, NIMH MH-48444] NR 71 TC 415 Z9 434 U1 2 U2 9 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 OCT PY 1994 VL 151 IS 10 BP 1409 EP 1416 PG 8 WC Psychiatry SC Psychiatry GA PJ937 UT WOS:A1994PJ93700003 PM 8092334 ER PT J AU BRAMSON, RT BRAMSON, RA AF BRAMSON, RT BRAMSON, RA TI CONFRONTING THE REALITIES OF A RADIOLOGISTS LIFE - A PRIMER ON SURVIVAL IN THE MANAGED HEALTH-CARE MARKET SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material C1 SUFFOLK UNIV,SCH MANAGEMENT,BOSTON,MA 02108. RP BRAMSON, RT (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,PEDIAT RADIOL SECT,WHITE II,BOSTON,MA 02114, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 1994 VL 163 IS 4 BP 783 EP 787 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH683 UT WOS:A1994PH68300004 PM 8092011 ER PT J AU DORMAN, RL WHITMAN, GJ CHEW, FS AF DORMAN, RL WHITMAN, GJ CHEW, FS TI HYPERSENSITIVITY VASCULITIS OF THE DUODENUM SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 5 TC 3 Z9 3 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 OCT PY 1994 VL 163 IS 4 BP 840 EP 840 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH683 UT WOS:A1994PH68300015 PM 8092020 ER PT J AU PALMER, WE AF PALMER, WE TI IN THE PATIENT WITH A SUSPECTED ROTATOR CUFF DISORDER, THE APPROPRIATE IMAGING STRATEGY BALANCES COST AND INVASIVENESS WITH THE NEED TO DETECT SUBTLE TENDINOUS ABNORMALITIES AND CAUSES OF MECHANICAL IMPINGEMENT - WHAT ARE THE BEST IMAGING OPTIONS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter RP PALMER, WE (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 3 Z9 3 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 OCT PY 1994 VL 163 IS 4 BP 990 EP 991 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH683 UT WOS:A1994PH68300051 PM 8092054 ER PT J AU BOSTWICK, DG ALGABA, F AMIN, MB AYALA, A EBLE, J GOLDSTEIN, N HELPAP, B HUMPHREY, P GRIGNON, D JONES, EC MCNEAL, J MONTIRONI, R QIAN, J RO, J SRIGLEY, J TETU, B TRONCOSO, P TRUE, L WHEELER, T YOUNG, RH AF BOSTWICK, DG ALGABA, F AMIN, MB AYALA, A EBLE, J GOLDSTEIN, N HELPAP, B HUMPHREY, P GRIGNON, D JONES, EC MCNEAL, J MONTIRONI, R QIAN, J RO, J SRIGLEY, J TETU, B TRONCOSO, P TRUE, L WHEELER, T YOUNG, RH TI CONSENSUS STATEMENT ON TERMINOLOGY - RECOMMENDATION TO USE ATYPICAL ADENOMATOUS HYPERPLASIA IN-PLACE OF ADENOSIS OF THE PROSTATE SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter C1 FUNDACIO PUIGVERT,BARCELONA,SPAIN. HENRY FORD HOSP,DETROIT,MI 48202. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. RICHARD L ROUDEBUSH VET AFFAIRS MED CTR,INDIANAPOLIS,IN 46202. INDIANA UNIV,INDIANAPOLIS,IN 46204. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. UNIV FREIBURG,ACAD HOSP,SINGEN,GERMANY. BARNES HOSP,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,ST LOUIS,MO. HARPER GRACE HOSP,DETROIT,MI 48201. WAYNE STATE UNIV,DETROIT,MI. UNIV BRITISH COLUMBIA,VANCOUVER,BC,CANADA. STANFORD UNIV,MED CTR,STANFORD,CA 94305. UNIV ANCONA,ANCONA,ITALY. BEIJING FRIENDSHIP HOSP,BEIJING,PEOPLES R CHINA. UNIV TORONTO,SUNNYBROOK HLTH SCI CTR,TORONTO,ON,CANADA. HOTEL DIEU QUEBEC,QUEBEC CITY,PQ,CANADA. UNIV WASHINGTON,SEATTLE,WA 98195. BAYLOR COLL MED,HOUSTON,TX 77030. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BOSTWICK, DG (reprint author), MAYO CLIN & MAYO FDN,200 1ST ST SW,ROCHESTER,MN 55905, USA. NR 2 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1994 VL 18 IS 10 BP 1069 EP 1070 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA PJ241 UT WOS:A1994PJ24100011 PM 7522413 ER PT J AU HOHNLOSER, SH KLINGENHEBEN, T SINGH, BN AF HOHNLOSER, SH KLINGENHEBEN, T SINGH, BN TI AMIODARONE-ASSOCIATED PROARRHYTHMIC EFFECTS - A REVIEW WITH SPECIAL REFERENCE TO TORSADE-DE-POINTES TACHYCARDIA SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID SUSTAINED VENTRICULAR-TACHYCARDIA; ARRHYTHMIA SUPPRESSION TRIAL; ANTIARRHYTHMIC DRUG-THERAPY; ACUTE MYOCARDIAL-INFARCTION; PLACEBO-CONTROLLED TRIAL; SUDDEN CARDIAC DEATH; LOW-DOSE AMIODARONE; LONG QT SYNDROME; TERM FOLLOW-UP; DE-POINTES AB Purpose: To assess the incidence of amiodarone-mediated aggravation of ventricular tachyarrhythmias or the development of new arrhythmias, such as torsade de pointes, in patients with cardiac disease. Data Sources and Study Selection: A MEDLINE literature search was done to identify articles published during the last 20 years that presented data on amiodarone-associated proarrhythmic events. The articles were divided into three categories: case reports, uncontrolled retrospective studies, and prospective controlled trials. In addition, articles were identified that examined the effects of amiodarone in patients with previously documented drug-induced torsade de pointes. Results: 65 English-language case reports dealing with torsade de pointes during amiodarone therapy were found in the literature. In many of these cases, other predisposing factors for the development of torsade de pointes were reported. Seventeen studies each reported data from at least 50 patients who were treated with amiodarone for at least 6 months. Of 2878 patients included in these trials, 57 were reported to have a proarrhythmic event while exposed to the drug (an overall incidence of 2%). Torsade de pointes was observed in one third of these patients (an overall incidence of 0.7%). In seven placebo-controlled trials in which the drug was given as monotherapy, amiodarone was not associated with the development of a proarrhythmic event in any patient. Finally, in three reports, 31 patients with previous drug-mediated torsade de pointes were exposed to amiodarone during short- and long-term therapy. In none of these patients did a recurrent episode of torsade de pointes develop, despite the amiodarone-induced prolongation of the QTc interval, which was equivalent to that observed at the time of torsade de pointes during exposure to previous drugs. Conclusions: Amiodarone appears to be associated with a remarkably low frequency of proarrhythmic events and an incidence of torsade de pointes of less than 1.0%. This low arrhythmogenicity and the negligible negative inotropic effect of the compound constitute properties that make amiodarone particularly useful in treating high-risk patients prone to sudden cardiac death. Its potential to reduce this risk is currently being evaluated in several large prospective trials. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP HOHNLOSER, SH (reprint author), UNIV FREIBURG,DEPT CARDIOL,HUGSTETTER STR 55,D-79106 FREIBURG,GERMANY. NR 79 TC 236 Z9 239 U1 0 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 1 PY 1994 VL 121 IS 7 BP 529 EP 535 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PJ102 UT WOS:A1994PJ10200009 PM 8067651 ER PT J AU GRINSPOON, S AF GRINSPOON, S TI AIDS - ENDOCRINOLOGIC AND METABOLIC CONSIDERATIONS SO ANNALS OF MEDICINE LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; PATHOLOGY; DISORDERS; VIRUS RP GRINSPOON, S (reprint author), MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,JACKSON 1021,BOSTON,MA 02114, USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0785-3890 J9 ANN MED JI Ann. Med. PD OCT PY 1994 VL 26 IS 5 BP 321 EP 323 DI 10.3109/07853899409148345 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA PM933 UT WOS:A1994PM93300003 PM 7826591 ER PT J AU UEKI, K RICHARDSON, EP HENSON, JW LOUIS, DN AF UEKI, K RICHARDSON, EP HENSON, JW LOUIS, DN TI IN-SITU POLYMERASE CHAIN-REACTION DEMONSTRATION OF JC VIRUS IN PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, INCLUDING AN INDEX CASE SO ANNALS OF NEUROLOGY LA English DT Note ID INSITU HYBRIDIZATION; DNA; AMPLIFICATION; BRAIN AB Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that is caused by JC papovavirus. The virus can be demonstrated in brains with PML using a variety of techniques. In situ polymerase chain reaction (PCR) is a new method that combines the sensitivity of PCR with the histological localization of in situ hybridization. We here show that in situ PCR can detect JC virus in archival tissue sections of 3 cases of PML, including 1 of the original cases described in 1958 and 1 case that was fixed in formalin for 7 weeks. JC virus DNA was amplified directly on tissue and demonstrated in the characteristic enlarged oligodendrocytes and bizarre astrocytes. These data illustrate the utility of the in situ PCR technique in detecting JC virus in archival sections, including those fixed for prolonged periods, and provide a historical footnote to the original report of PML. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA 02114. FU NCI NIH HHS [CA 57683]; NINDS NIH HHS [NS 1650] NR 13 TC 16 Z9 17 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 OCT PY 1994 VL 36 IS 4 BP 670 EP 673 DI 10.1002/ana.410360421 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PM607 UT WOS:A1994PM60700020 PM 7944303 ER PT J AU LEWIS, ML WEBER, AL MCKENNA, MJ AF LEWIS, ML WEBER, AL MCKENNA, MJ TI REPARATIVE CELL GRANULOMA OF THE TEMPORAL BONE SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Note ID LESIONS; TUMOR; SKULL C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP LEWIS, ML (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 12 TC 19 Z9 22 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 1994 VL 103 IS 10 BP 826 EP 828 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA PL371 UT WOS:A1994PL37100015 PM 7944177 ER PT J AU BODE, BP SOUBA, WW AF BODE, BP SOUBA, WW TI MODULATION OF CELLULAR PROLIFERATION ALTERS GLUTAMINE TRANSPORT AND METABOLISM IN HUMAN HEPATOMA-CELLS SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 114th Annual Scientific-Session of the American-Surgical-Association CY APR 07-09, 1994 CL SAN ANTONIO, TX SP AMER SURG ASSOC ID AMINO-ACID TRANSPORT; RAT-LIVER; NITROGEN-METABOLISM; SYSTEM ASC; EXPRESSION; HEPATOCYTES; RELEVANCE; CARCINOMA; CYCLE; LINE AB Objective The authors determined the effects of growth inhibition on glutamine transport and metabolism in human hepatoma cells. Summary Background Data Hepatoma cells exhibit markedly higher (10- to 30-fold) glutamine uptake than normal human hepatocytes, via a disparate transporter protein with a higher affinity for glutamine. Currently, little is known about the effects of growth arrest on glutamine transport and metabolism in hepatoma cells. Methods The authors determined proliferation rates, glutamine transport, and glutaminase activities in the human hepatoma cell lines HepG2, Huh-7, and SK-Hep, both in the presence and absence of the chemotherapeutic agents novobiocin and sodium butyrate. The transport activities for alanine, arginine, and leucine also were determined in both treated and untreated cells. Glutaminase activity was determined in normal human liver tissue and compared with that present in hepatoma cells. Results Glutaminase activities were similar in all three cell lines studied, despite differences in proliferation rates, and were sixfold higher than the activity in normal human liver. In contrast to normal hepatocytes, which expressed the liver-specific glutaminase, hepatomas expressed the kidney-type isoform. Sodium butyrate (1 mmol/L) and novobiocin (0.1 mmol/L) inhibited cellular proliferation and reduced both glutamine transport and glutaminase activity by more than 50% after 48 hours in the faster-growing, less differentiated SK-Hep cells. In contrast, the agents required 72 hours to attenuate glutamine uptake by 30% and 50% in the slower-growing, more differentiated HepG2 and Huh-7 cell lines, respectively. Treatment of all three cell lines with novobiocin/butyrate also resulted in a 30% to 60% attenuation of the transport of alanine, arginine, and leucine, and glutamine, indicating that inhibition of cellular proliferation similarly affects disparate amino acid transporters. Conclusions Hepatocellular transformation is characterized by a marked increase in glutamine transport and metabolism. Inhibition of cellular proliferation attenuates glutamine transport and metabolism. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV SURG ONCOL,BOSTON,MA 02114. FU NCI NIH HHS [CA45327] NR 22 TC 35 Z9 35 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD OCT PY 1994 VL 220 IS 4 BP 411 EP 424 DI 10.1097/00000658-199410000-00001 PG 14 WC Surgery SC Surgery GA PL393 UT WOS:A1994PL39300001 PM 7944654 ER PT J AU AKINS, CW AF AKINS, CW TI EARLY AND LATE RESULTS FOLLOWING EMERGENCY ISOLATED MYOCARDIAL REVASCULARIZATION DURING HYPOTHERMIC FIBRILLATORY ARREST - EVENT-FREE SURVIVAL FOLLOWING NONEMERGENCY MYOCARDIAL REVASCULARIZATION DURING HYPOTHERMIC FIBRILLATORY ARREST - UPDATED IN 1994 SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material RP AKINS, CW (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,CARDIAC SURG UNIT,WHITE 503,BOSTON,MA 02114, USA. NR 4 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 1994 VL 58 IS 4 BP 1205 EP 1206 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PL572 UT WOS:A1994PL57200067 PM 7944788 ER PT J AU OROURKE, TJ WEISS, GR NEW, P BURRIS, HA RODRIGUEZ, G ECKHARDT, J HARDY, J KUHN, JG FIELDS, S CLARK, GM VONHOFF, DD AF OROURKE, TJ WEISS, GR NEW, P BURRIS, HA RODRIGUEZ, G ECKHARDT, J HARDY, J KUHN, JG FIELDS, S CLARK, GM VONHOFF, DD TI PHASE-I CLINICAL-TRIAL OF ORMAPLATIN (TETRAPLATIN, NSC-363812) SO ANTI-CANCER DRUGS LA English DT Article DE NEUROTOXICITY; ORMAPLATIN; PHASE I TRIAL ID CARCINOMA CELL-LINES; OVARIAN-CANCER; PERIPHERAL NEUROTOXICITY; CISPLATIN NEUROTOXICITY; PLATINUM ANALOGS; SENSITIVITY; RESISTANCE; NEUROPATHY; COMPLEXES; TOXICITY AB Ormaplatin is a platinum analog that was developed because of an altered toxicity profile and non-cross resistance to cisplatin in both in vitro and in vivo models. To determine the toxicities and maximum tolerated dose of ormaplatin on a daily times five schedule, patients with refractory solid tumors received ormaplatin on five consecutive days at nine dose levels ranging from 1.0 to 15.0 mg/m(2)/day. A total of 35 patients received 70 cycles of therapy. Nausea and vomiting and myelosuppression were moderate and not dose-limiting. Dose-limiting neurotoxicity, consisting of a sensory peripheral neuropathy, was seen in all five patients who received cumulative doses greater than or equal to 165 mg/m(2). This neurotoxicity was symptomatic in all patients and caused significant functional impairment in four patients with inability to walk in two patients. A sensitive atomic absorption spectroscopy analysis performed for one patient at the 13.0 mg/m(2)/day dose level showed a Cp(max) of 163 ng/ml and a t(1/2) of 10.9 min for free platinum. A phase II dose could not be determined due to the onset of peripheral neuropathy at low cumulative doses and not at absolute dose levels. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. CANC THERAPY & RES CTR S TEXAS,SAN ANTONIO,TX 78229. RP OROURKE, TJ (reprint author), BROOKE ARMY MED CTR,HEMATOL ONCOL SERV,FT SAM HOUSTON,TX 78234, USA. FU NCI NIH HHS [P01-CA54-174-02, CM 07305-01]; NCRR NIH HHS [5M01RR01346-09] NR 27 TC 33 Z9 33 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD OCT PY 1994 VL 5 IS 5 BP 520 EP 526 DI 10.1097/00001813-199410000-00002 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA PM436 UT WOS:A1994PM43600002 PM 7858283 ER PT J AU HAGEGE, A DESNOS, M KOMAJDA, M DUBOURG, O ISNARD, R GUICHENEY, P SCHWARTZ, K LEVINE, RA AF HAGEGE, A DESNOS, M KOMAJDA, M DUBOURG, O ISNARD, R GUICHENEY, P SCHWARTZ, K LEVINE, RA TI PHYSIOPATHOLOGY OF MITRAL-VALVE MECHANICS IN HYPERTROPHIC CARDIOMYOPATHY SO ARCHIVES DES MALADIES DU COEUR ET DES VAISSEAUX LA French DT Article ID OUTFLOW TRACT OBSTRUCTION; LEAFLET; GENE AB Ventricular hypertrophy, the only indisputable phenotypical marker of hypertrophic cardiomyopathy, is the basis of the physiopathology and treatment of the disease. Mitral valve abnormalities are usually considered to be secondary to the hypertrophy but the genesis of systolic anterior motion by the Venturi effect has been questioned by many clinical and experimental observations. Abnormalities of the mitral valve apparatus, may in themselves (elongation of the valves, antero-internal malposition of the mitral papillary muscles and/or hyperlaxicity of antero-internal corhdae tendinae) create systolic anterior motion or subaortic obstruction in the absence of septal hypertrophy and/or increased subaortic flow velocities. Anatomo-clinical studies have confirmed this hypothesis: a high prevalence of mitral valve disease (increased valvular surface and length) has been found in hypertrophic cardiomyopathy. ??le recognition of these abnormalities is of value from the therapeutic (mitral valvuloplasty) diagnostic (in borderline cases) and genetic (when the primary nature of the abnormalities is confirmed) points of view. C1 HOP LA PITIE SALPETRIERE,F-75013 PARIS,FRANCE. HOP AMBROISE PARE,F-92104 BOULOGNE,FRANCE. HOP LA PITIE SALPETRIERE,INSERM,U153,F-75013 PARIS,FRANCE. MASSACHUSETTS GEN HOSP,NONINVAS CARDIAC LAB,BOSTON,MA. RP HAGEGE, A (reprint author), HOP BOUCICAULT,SERV CARDIOL,78 RUE CONVENT,F-75730 PARIS 15,FRANCE. NR 26 TC 5 Z9 5 U1 0 U2 1 PU J B BAILLIERE PI PARIS PA 46, RUE LA BOETIE, 75379 PARIS, FRANCE SN 0003-9683 J9 ARCH MAL COEUR VAISS JI Arch. Mal. Coeur Vaiss. PD OCT PY 1994 VL 87 IS 10 BP 1345 EP 1352 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PR857 UT WOS:A1994PR85700011 PM 7771880 ER PT J AU FOITZIK, T LEWANDROWSKI, KB FERNANDEZDELCASTILLO, C RATTNER, DW KLAR, E WARSHAW, AL AF FOITZIK, T LEWANDROWSKI, KB FERNANDEZDELCASTILLO, C RATTNER, DW KLAR, E WARSHAW, AL TI EXOCRINE HYPERSTIMULATION BUT NOT PANCREATIC DUCT OBSTRUCTION INCREASES THE SUSCEPTIBILITY TO ALCOHOL-RELATED PANCREATIC INJURY SO ARCHIVES OF SURGERY LA English DT Article ID RAT; STIMULATION; CERULEIN; CHOLECYSTOKININ; PATHOGENESIS; SECRETION AB Objective: To evaluate the factors thought to be involved in the pathogenesis of acute pancreatitis associated with alcohol. Background: The mechanism of alcohol-induced pancreatitis is believed to involve synergistic effects of various pathogenetic factors. The present study was designed to evaluate the possible contribution of pancreatic duct obstruction, physiologic exocrine stimulation, or secretory hyperstimulation to alcohol-induced pancreatic injury. Methods: Wistar rats were allocated randomly to a control group (group 1), or to a group with pancreatic duct obstruction (group 2), physiologic exocrine stimulation (group 3), ductal obstruction and exocrine stimulation (group 4), or exocrine hyperstimulation with the cholecystokinin analogue cerulein (group 5). Three hours after this pretreatment, animals in each experimental group were randomly divided into two subgroups for intragastric administration of either water (groups 1A through 5A) or beer (groups 1B through 5B). Test solutions were instilled over 9 hours (total amount of alcohol administered, 4.8 g/kg). Twenty-four hours after beginning the test infusion, animals were killed for histologic evaluation of pancreatic edema and determination of an acinar cell necrosis score. Serum amylase levels were determined at 3, 9, and 24 hours. Results: No increase in amylase levels or significant morphologic changes were found in control animals (group 1A) or in animals subjected to physiologic exocrine stimulation (group 2A). Pancreatic duct obstruction, with or without physiologic exocrine hyperstimulation (groups 3A and 4A), and exocrine hyperstimulation (group 5A) induced pancreatitis of similar severity with minor acinar cell damage. Alcohol superimposed on exocrine hyperstimulation (group 5B) increased acinar cell injury (group 5A, 0.4+/-0.1 points vs 5B, 1.0+/-0.2 points; P<.05) and serum amylase levels at 24 hours (group 5a, 41+/-6 U/L vs group 5B, 72+/-11 U/L; P<.O5), whereas no differences between subgroups A and B (water vs beer) were found in groups 1 through 4. Conclusion: Our findings suggest that the pathogenesis of acute alcoholic pancreatitis may require a state of exocrine hyperstimulation, perhaps via cholecystokinin, but do not support a role for constriction or obstruction of Oddi's sphincter. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV HEIDELBERG,DEPT SURG,W-6900 HEIDELBERG,GERMANY. NR 25 TC 19 Z9 19 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 OCT PY 1994 VL 129 IS 10 BP 1081 EP 1085 PG 5 WC Surgery SC Surgery GA PL493 UT WOS:A1994PL49300018 PM 7944939 ER PT J AU TALAL, N AF TALAL, N TI ONCOGENES, AUTOGENES, AND RHEUMATIC DISEASES SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID AUTOIMMUNE-DISEASE; SALIVARY-GLAND; FAS ANTIGEN; LPR MICE; APOPTOSIS; INFECTION; CELLS; GENE; LYMPHOCYTES; EXPRESSION C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP TALAL, N (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN IMMUNOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDCR NIH HHS [DEO9311-03] NR 21 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1994 VL 37 IS 10 BP 1421 EP 1422 DI 10.1002/art.1780371003 PG 2 WC Rheumatology SC Rheumatology GA PM444 UT WOS:A1994PM44400002 PM 7945465 ER PT J AU GRINSPOON, SK DONOVAN, DS BILEZIKIAN, JP AF GRINSPOON, SK DONOVAN, DS BILEZIKIAN, JP TI ETIOLOGY AND PATHOGENESIS OF HORMONAL AND METABOLIC DISORDERS IN HIV-INFECTION SO BAILLIERES CLINICAL ENDOCRINOLOGY AND METABOLISM LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; NECROSIS-FACTOR-ALPHA; LEYDIG-CELL STEROIDOGENESIS; HUMAN GROWTH-HORMONE; VIRUS INFECTION; AIDS PATIENTS; ADRENOCORTICAL INSUFFICIENCY; BINDING GLOBULIN; ADRENAL-FUNCTION C1 COLUMBIA UNIV, COLL PHYS & SURG, NEW YORK, NY 10032 USA. RP GRINSPOON, SK (reprint author), MASSACHUSETTS GEN HOSP, NEUROCRINE UNIT, JACKSON 1021, BOSTON, MA 02114 USA. NR 98 TC 18 Z9 18 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-351X J9 BAILLIERE CLIN ENDOC JI Baillieres Clin. Endocrinol. Metab. PD OCT PY 1994 VL 8 IS 4 BP 735 EP 755 DI 10.1016/S0950-351X(05)80297-6 PG 21 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PK929 UT WOS:A1994PK92900002 PM 7811218 ER PT J AU FEENER, EP SHIBA, T HU, KQ WILDEN, PA WHITE, MF KING, GL AF FEENER, EP SHIBA, T HU, KQ WILDEN, PA WHITE, MF KING, GL TI CHARACTERIZATION OF PHORBOL ESTER-STIMULATED SERINE PHOSPHORYLATION OF THE HUMAN INSULIN-RECEPTOR SO BIOCHEMICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; VASCULAR ENDOTHELIAL-CELLS; BETA-SUBUNIT; THREONINE PHOSPHORYLATION; JUXTAMEMBRANE REGION; AMINO-ACIDS; TYROSINE; AUTOPHOSPHORYLATION; SEQUENCE; BINDING AB Phorbol 12-myristate 13-acetate (PMA)-stimulated phosphorylation of the human insulin receptor (IR) was characterized and compared in two cell types of different lineage: normal rat kidney epithelial (NRK) cells and Chinese hamster ovary (CHO) fibroblasts. PMA stimulation increased IR beta-subunit phosphorylation to 252 +/- 43 and 259 +/- 47 % (+/- S.D.) of the unstimulated control in NRK and CHO cells respectively. Tryptic phosphopeptide analysis by Tricine/SDS/PAGE revealed significant differences in the PMA-stimulated phosphorylation of the IR in these two cell types. This phosphorylation of the IR was predominantly located in two tryptic phosphopeptides, and these phosphopeptides were absent in an IR mutant truncated by 43 C-terminal amino acids. The major PMA-stimulated tryptic phosphopeptide from in vivo-labelled CHO/IR was immunoprecipitated with an antibody against residues Ser(1315) to Lys(1329), and this precipitation was blocked with excess unlabelled peptide containing this sequence. Radiosequencing by manual Edman degradation revealed that this tryptic phosphopeptide was phosphorylated at Ser(1315). This PMA-stimulated phosphorylation did not inhibit autophosphorylation of the IR in vivo. These results demonstrate that PMA-stimulated phosphorylation of the IR can exhibit significant differences when expressed in different cell types, and that Ser(1315) is a major PMA-stimulated phosphorylation site on the human IR. RP FEENER, EP (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [P30 DK036836, DK36836, DK36433] NR 40 TC 16 Z9 16 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 OCT 1 PY 1994 VL 303 BP 43 EP 50 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PL764 UT WOS:A1994PL76400007 PM 7945263 ER PT J AU RAHMAN, MU KLEYMAN, TR MCENTEE, CM HUDSON, AP AF RAHMAN, MU KLEYMAN, TR MCENTEE, CM HUDSON, AP TI REGULATION OF MITOCHONDRIAL CAMP-DEPENDENT PROTEIN-KINASE ACTIVITY IN YEAST SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article ID AMP RECEPTOR PROTEIN; CYCLIC-AMP; SACCHAROMYCES-CEREVISIAE; BINDING PROTEIN; TRANSCRIPTION FACTOR; STRINGENT RESPONSE; PHOSPHORYLATION; SUBUNIT; IMPORT; GENES AB We have shown that transcription of the yeast (S. cerevisiae) mitochondrial (mt) genome is cAMP-sensitive, via a mt cAMP-dependent protein kinase (cAPK). In relation to that work, we examined whether the BCY1 gene product functions as regulatory subunit for mt cAPK, as it does for the cytoplasmic enzyme. We demonstrate that mt protein extracts from a bcy1 strain show no cAPK activity, whereas similar extracts from an otherwise isochromosomal BCY1 strain show high levels of such activity. Partial purification of mt cAPK from each strain confirms this difference. Photoaffinity labeling with 8-N-3[P-32]cAMP and highly-purified mt protein extracts from the BCY1 strain identifies one cAMP-binding protein (M(r) approximate to 47000), while similar mt extracts from the bcy1 strain lack all cAMP-binding proteins. These data suggest that BCY1 regulates yeast mt cAPK, and that inactivation of BCY1 removes that mt activity from cAMP control. C1 UNIV PENN,SCH MED,COLL MED,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PHYSIOL,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,MED RES SERV,PHILADELPHIA,PA 19104. NR 36 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD OCT PY 1994 VL 34 IS 4 BP 745 EP 753 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PT217 UT WOS:A1994PT21700013 PM 7866301 ER PT J AU SOCRANSKY, SS SMITH, C MARTIN, L PASTER, BJ DEWHIRST, FE LEVIN, AE AF SOCRANSKY, SS SMITH, C MARTIN, L PASTER, BJ DEWHIRST, FE LEVIN, AE TI CHECKERBOARD DNA-DNA HYBRIDIZATION SO BIOTECHNIQUES LA English DT Note ID SUBGINGIVAL MICROORGANISMS AB A method is introduced for hybridizing large numbers of DNA samples against large numbers of DNA probes on a single support membrane. Denatured DNA from up to 43 samples was fixed in separate lanes on a single membrane mounted in a Miniblotter(R) 45. The membrane was then rotated 90 degrees in the same device, which enabled simultaneous hybridization with 43 different DNA probes. Hybridizations were also performed on lysates of bacterial cells blotted to membranes. A miniSlot(TM) device allowed lysates loaded in parallel channels to be aspirated through the membrane, depositing horizontal lanes on the membrane surface. Hybridizations were performed in vertical lanes with either digoxigenin-labeled whole genomic probes or 16S rRNA-based oligonucleotide probes directly conjugated to alkaline phosphatase. The method permits the simultaneous determination of the presence of multiple bacterial species in single or multiple dental plaque samples, thus suggesting its usefulness for a range of clinical or environmental samples. C1 IMMUNET,CAMBRIDGE,MA. RP SOCRANSKY, SS (reprint author), FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04881, DE-08303, DE-10374] NR 12 TC 444 Z9 454 U1 2 U2 16 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD OCT PY 1994 VL 17 IS 4 BP 788 EP 792 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PK379 UT WOS:A1994PK37900043 PM 7833043 ER PT J AU PICHERT, G ALYEA, EP SOIFFER, RJ ROY, DC RITZ, J AF PICHERT, G ALYEA, EP SOIFFER, RJ ROY, DC RITZ, J TI PERSISTENCE OF MYELOID PROGENITOR CELLS EXPRESSING BCR-ABL MESSENGER-RNA AFTER ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR CHRONIC MYELOGENOUS LEUKEMIA SO BLOOD LA English DT Note ID POLYMERASE CHAIN-REACTION; VERSUS-HOST DISEASE; MINIMAL RESIDUAL DISEASE; PHILADELPHIA-CHROMOSOME; CHRONIC PHASE; CLINICAL-SIGNIFICANCE; LYMPHOCYTES-T; GENE; REARRANGEMENT; RELAPSE AB Previous studies have shown that tumor-specific bcr-abl mRNA can often be detected by polymerase chain reaction (PCR) for months to years after allogeneic bone marrow transplantation (BMT) for chronic myelocytic leukemia (CML). Nevertheless, the presence of bcr-abl mRNA by itself does not invariably predict for clinical relapse post-BMT. This has led to the hypothesis that bcr-abl mRNA might be expressed in cells that have lost either proliferative or myeloid differentiation potential. To directly characterize the cells detected by PCR in patients with CML after allogeneic BMT, we first identified five individuals in whom PCR-positive cells could be detected at multiple times post-BMT. Bone marrow samples from these individuals were cultured in vitro and single erythroid, granulocytic, and macrophage colonies, each containing 50 to 100 cells, were examined for the presence of bcr-abl mRNA by PCR. PCR-positive myeloid colonies could be detected in four of five individuals in marrow samples obtained 5 to 56 months post-BMT. Overall, 7 of 135 progenitor cell colonies (5.2%) were found to be PCR-positive. The expression of bcr-abl mRNA appeared to be equally distributed among committed erythroid, macrophage, and granulocyte progenitors. These patients have now been followed-up for an additional 20 to 33 months from the time of progenitor cell PCR analysis but only one of these individuals has been found to have cytogenetic evidence of recurrent Ph(+) cells. These results show that long-term persistence of PCR-detectable bcr-abl mRNA after allogeneic BMT can be caused by the persistence of CML-derived clonogenic myeloid precursors that have survived the BMT preparative regimen. These cells continue to have both proliferative and myeloid differentiation capacity in vitro. Nevertheless. these PCR-positive cells do not appear to either expand or differentiate in vivo for prolonged periods, suggesting the presence of mechanisms for suppression of residual clonogenic leukemia cells in vivo. (C) 1994 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. UNIV MONTREAL,HOP MAISON NEUVE ROSEMONT,DEPT MED,UNITE TRANSPLANTAT MOELLE OSSEUSE,MONTREAL,PQ,CANADA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI29530] NR 36 TC 31 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1994 VL 84 IS 7 BP 2109 EP 2114 PG 6 WC Hematology SC Hematology GA PK125 UT WOS:A1994PK12500004 PM 7919323 ER PT J AU CHAUHAN, D KHARBANDA, S UCHIYAMA, H URASHIMA, M FRAGOSO, R SEN, J KUFE, DW ANDERSON, KC AF CHAUHAN, D KHARBANDA, S UCHIYAMA, H URASHIMA, M FRAGOSO, R SEN, J KUFE, DW ANDERSON, KC TI IDENTIFICATION OF UPSTREAM SIGNALS REGULATING INTERLEUKIN-6 GENE-EXPRESSION DURING IN-VITRO TREATMENT OF HUMAN B-CELLS WITH POKEWEED MITOGEN SO BLOOD LA English DT Article ID NF-KAPPA-B; PROTEIN TYROSINE PHOSPHORYLATION; IMMEDIATE-EARLY GENE; DNA-BINDING SUBUNIT; C-FOS; LYMPHOCYTES-B; GROWTH-FACTOR; MOLECULAR-CLONING; ANTIGEN RECEPTOR; MAP KINASE AB The present studies have characterized the regulation of interleukin-6 (IL-6) gene expression during pokeweed mitogen (PWM)-driven human B-cell differentiation. PWM induced an early and transient increase in the expression of immediate-early response genes of the jun/fos leucine zipper family (c-jun, jun B, c-fos, and fos B). The induction of c-jun mRNA by PWM was concentration dependent. Nuclear run-on assays showed that PWM treatment is associated with an increased rate of c-jun gene transcription. The induction of c-jun mRNA precedes the induction of IL-6 gene expression and IL-6 secretion by the B cells. c-Jun antisense, but not sense, oligodeoxynucleotide (ODN) significantly decreases PWM-related B-cell (1) proliferation; (2) IL-6 mRNA induction; (3) IL-6 secretion; and (4) nuclear extract binding to AP-1 in electrophoretic mobility shift assay. In contrast, c-Fos antisense ODN did not effect either IL-6 mRNA induction or IL-6 secretion triggered in B cells by PWM. The results further show activation of c-Raf-l kinase in PWM-treated B cells. Raf-l acts upstream to mitogen-activated protein (MAP) kinase: therefore, studies were performed to assay for MAP kinase activation in these cells. The results show an increase in phosphorylation of myelin basic protein (MBP) and c-Jun ''Y'' peptide in PWM-treated B cells. Taken together, these findings suggest that PWM is able to initiate an intracytoplasmic signaling cascade in normal human splenic B cells, which, at least in part, involves serine/threonine protein kinases. These results show transient induction of immediate-early response genes in B cells and support a potential role for the c-jun gene product in regulation of IL-6 transcription and secretion. (C) 1994 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NCI NIH HHS [CA 50947] NR 55 TC 22 Z9 22 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 1994 VL 84 IS 7 BP 2243 EP 2252 PG 10 WC Hematology SC Hematology GA PK125 UT WOS:A1994PK12500024 PM 7919342 ER PT J AU MIHELCIC, D SCHLEIFFENBAUM, B TEDDER, TF SHARAR, SR HARLAN, JM WINN, RK AF MIHELCIC, D SCHLEIFFENBAUM, B TEDDER, TF SHARAR, SR HARLAN, JM WINN, RK TI INHIBITION OF LEUKOCYTE L-SELECTIN FUNCTION WITH A MONOCLONAL-ANTIBODY ATTENUATES REPERFUSION INJURY TO THE RABBIT EAR SO BLOOD LA English DT Article ID ADHESION MOLECULE-1 LAM-1; MEDIATED LUNG INJURY; NODE HOMING RECEPTOR; ENDOTHELIAL-CELLS; P-SELECTIN; NEUTROPHIL ADHESION; CHEMOTACTIC FACTORS; HYDROGEN-PEROXIDE; OXYGEN RADICALS; INVITRO MODEL AB The leukocyte adhesion molecule L-selectin mediates neutrophil adhesive interactions with endothelial cells and is in part responsible for neutrophil rolling. We examined the role of L-selectin in ischemia-reperfusion injury of rabbit ears using a monoclonal antibody (MoAb) directed to a functional epitope of L-selectin. Arterial blood flow to the rabbit ear was occluded for six hours with ambient temperature at 23 degrees C to 24 degrees C. Rabbits were treated at reperfusion with saline (n = 8), the L-selectin function-blocking LAM1-3 MoAb (2 mg/kg), or the nonfunction-blocking LAM1-14 MoAb (2 mg/ kg). Tissue injury was determined by measuring edema and necrosis. Edema in the LAM1-3 MoAb-treated group (peak = 25 +/- 4 mL) was significantly less (P < .05) than in saline-treated (peak = 40 +/- 8 mL) and LAM1-14 MoAb-treated (peak = 41 +/- 6 mL) groups. Tissue necrosis at 7 days was not observed in the LAM1-3 MoAb-treated group, whereas significant necrosis (P < .05) was seen in the saline- (8% +/- 3% necrosis) and LAM1-14 MoAb-treated (7% +/- 3% necrosis) group. We conclude that blocking L-selectin ameliorates necrosis and edema after ischemia and reperfusion in the rabbit ear, presumably by blocking neutrophil rolling. (C) 1994 by The American Society of Hematology. C1 UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT SURG ZA16,SEATTLE,WA 98104. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98104. UNIV WASHINGTON,DEPT PHYSIOL BIOPHYS,SEATTLE,WA 98104. UNIV WASHINGTON,DEPT ANESTHESIOL,SEATTLE,WA 98195. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-54464]; NHLBI NIH HHS [HL-43141]; NIGMS NIH HHS [GM-42686] NR 51 TC 52 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 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 1994 VL 84 IS 7 BP 2322 EP 2328 PG 7 WC Hematology SC Hematology GA PK125 UT WOS:A1994PK12500034 PM 7522626 ER PT J AU KOSSLYN, SM ALPERT, NM THOMPSON, WL CHABRIS, CF RAUCH, SL ANDERSON, AK AF KOSSLYN, SM ALPERT, NM THOMPSON, WL CHABRIS, CF RAUCH, SL ANDERSON, AK TI IDENTIFYING OBJECTS SEEN FROM DIFFERENT VIEWPOINTS - A PET INVESTIGATION SO BRAIN LA English DT Article DE OBJECT IDENTIFICATION; PET; VISION ID POSITRON EMISSION TOMOGRAPHY; EXTRASTRIATE CORTEX; VISUAL-CORTEX; ATTENTION; RECOGNITION; DISSOCIATION; MEMORY; PICTURES; NEURONS; MACAQUE AB Positron emission tomography scans were acquired when subjects performed three tasks, each in a separate block of trials. They decided whether words named pictures of objects viewed from a canonical perspective, decided whether words named pictures of objects viewed from a non-canonical (unusual) perspective or saw random patterns of lines and pressed a pedal when they heard the word (this was a baseline condition). The dorsolateral prefrontal region was activated when subjects identified objects seen from noncanonical perspectives, as expected if-the frontal lobes are involved in top-down perceptual processing. In addition, several areas in the occipital, temporal and parietal lobes were selectively activated when subjects identified objects seen from non-canonical perspectives, as specifically predicted by a recent theory. Overall, the pattern of results supported the view that the human brain identifies objects by using a system of areas similar to that suggested by studies of other primates. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RP KOSSLYN, SM (reprint author), HARVARD UNIV,DEPT PSYCHOL,33 KIRKLAND ST,CAMBRIDGE,MA 02138, USA. NR 72 TC 194 Z9 194 U1 0 U2 6 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 1994 VL 117 BP 1055 EP 1071 DI 10.1093/brain/117.5.1055 PN 5 PG 17 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QP367 UT WOS:A1994QP36700012 PM 7953588 ER PT J AU LEVINE, RA GARDNER, JC FULLERTON, BC STUFFLEBEAM, SM FURST, M ROSEN, BR AF LEVINE, RA GARDNER, JC FULLERTON, BC STUFFLEBEAM, SM FURST, M ROSEN, BR TI MULTIPLE-SCLEROSIS LESIONS OF THE AUDITORY PONS ARE NOT SILENT SO BRAIN LA English DT Article DE INTERAURAL DISCRIMINATION; SPEECH DISCRIMINATION; MASKING LEVEL DIFFERENCE; EVOKED POTENTIALS ID HUMAN BRAIN-STEM; EVOKED-POTENTIALS; NERVE FIBERS; CONSONANT RECOGNITION; BACKGROUND-NOISE; RESPONSES; SPEECH; VOWELS; REPRESENTATION; PATTERNS AB To understand the relationship between brainstem lesions and auditory neurology in patients with multiple sclerosis, we compared behavioural, electrophysiological and imaging data in 38 patients with probable or definite multiple sclerosis and normal or near normal hearing. Behavioural measures included (i) general hearing tests (audiogram, speech discrimination) and (ii) hearing tests likely to be critically dependent upon brainstem processing (masking level difference, and level discrimination). Brainstem potentials provided the electrophysiological data. Multiplanar high-resolution MRI of the brainstem provided the anatomical data. Interaural time discrimination for high-frequency sounds was by far the most sensitive of all tests with abnormalities in 71% of all subjects. Whenever any other test was abnormal this test was always abnormal. Interaural time discrimination for low-frequency sounds and evoked potentials were closely related and next most sensitive with abnormalities in similar to 40% of all subjects. Interaural level discrimination and masking level difference were least sensitive with abnormalities in <10% of subjects. Speech discrimination scores correlated significantly with the masking level differences, as well as with interaural time discrimination for high-frequency sounds. Pontine lesions were found in five of the 16 patients, in whom an objective method for detecting magnetic resonance lesions could be applied. All four with lesions involving the pontine auditory pathway had marked abnormalities in interaural time discrimination and evoked potentials. None of the other 12 had evoked potentials abnormalities. We conclude that neurological tests requiring precise neural timing can reveal behavioural deficits for multiple sclerosis lesions of the auditory pens that are otherwise 'silent'. Of all neurological systems the auditory system at the level of the pens is probably the most sensitive to multiple sclerosis lesions, because of its exceptional dependence upon neural timing in the microsecond range and the lack of redundancy in the encoding of high-frequency sounds. Precise neural timing may be critical for some aspects of speech processing. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. MIT, CAMBRIDGE, MA 02139 USA. TEL AVIV UNIV, IL-69978 TEL AVIV, ISRAEL. RP MASSACHUSETTS EYE & EAR INFIRM, EATON PEABODY LAB, 243 CHARLES ST, BOSTON, MA 02114 USA. FU NIDCD NIH HHS [P01 DC00119, T32 DC00006] NR 52 TC 12 Z9 12 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD OCT PY 1994 VL 117 BP 1127 EP 1141 DI 10.1093/brain/117.5.1127 PN 5 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA QP367 UT WOS:A1994QP36700018 PM 7953594 ER PT J AU CAPLAN, D WATERS, GS AF CAPLAN, D WATERS, GS TI SYNTACTIC PROCESSING IN SENTENCE COMPREHENSION BY APHASIC PATIENTS UNDER DUAL-TASK CONDITIONS SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPSYCHOL LAB,BOSTON,MA 02114. MCGILL UNIV,SCH COMMUN SCI DISORDERS,MONTREAL H3A 2T5,QUEBEC,CANADA. NR 9 TC 9 Z9 9 U1 2 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 1994 VL 47 IS 3 BP 397 EP 399 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA PM042 UT WOS:A1994PM04200028 ER PT J AU BUCHANAN, L HILDEBRANDT, N MACKINNON, GE AF BUCHANAN, L HILDEBRANDT, N MACKINNON, GE TI IMPLICIT PHONOLOGICAL KNOWLEDGE IN DEEP DYSLEXIA SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 UNIV WATERLOO,DEPT PSYCHOL,WATERLOO N2L 3G1,ONTARIO,CANADA. MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 8 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 1994 VL 47 IS 3 BP 435 EP 437 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA PM042 UT WOS:A1994PM04200042 ER PT J AU PALUMBO, CL FITZPATRICK, PM NAESER, MA MIMURA, M PRETE, MN SAMARAWEERA, R ALBERT, ML AF PALUMBO, CL FITZPATRICK, PM NAESER, MA MIMURA, M PRETE, MN SAMARAWEERA, R ALBERT, ML TI INCREASE IN LESION SIZE ON CT SCAN IN CHRONIC APHASIA PATIENTS WITH IMPROVED NAMING ABILITY SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,DEPT NEUROL,APHASIA RES CTR,BOSTON,MA 02118. VET AFFAIRS MED CTR,NEUROL SERV,BOSTON,MA. VET AFFAIRS MED CTR,RADIOL SERV,BOSTON,MA. TUFTS UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02111. VET AFFAIRS MED CTR,SPEECH PATHOL SERV,BOSTON,MA. US DEPT VET AFFAIRS,MED RES SERV,WASHINGTON,DC. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 1994 VL 47 IS 3 BP 491 EP 493 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA PM042 UT WOS:A1994PM04200062 ER PT J AU WATERS, GS CAPLAN, D AF WATERS, GS CAPLAN, D TI SYNTACTIC PROCESSING IN SENTENCE COMPREHENSION UNDER DUAL-TASK CONDITIONS SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID WORKING MEMORY; INDIVIDUAL-DIFFERENCES C1 MCGILL UNIV,SCH COMMUN SCI & DISORDERS,MONTREAL H3A 2T5,QUEBEC,CANADA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPSYCHOL LAB,BOSTON,MA 02114. NR 12 TC 3 Z9 3 U1 1 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 1994 VL 47 IS 3 BP 515 EP 518 PG 4 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA PM042 UT WOS:A1994PM04200070 ER PT J AU CAVINESS, VS AF CAVINESS, VS TI NEURONAL GROWTH AND DEVELOPMENT - A PROSPECTIVE SO BRAIN PATHOLOGY LA English DT Editorial Material RP CAVINESS, VS (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1994 VL 4 IS 4 BP 295 EP 295 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA PK299 UT WOS:A1994PK29900004 ER PT J AU LOUIS, DN HEDLEYWHYTE, ET AF LOUIS, DN HEDLEYWHYTE, ET TI THE GENETIC-BASIS OF HUMAN BRAIN-TUMORS - AN UPDATE SO BRAIN PATHOLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP LOUIS, DN (reprint author), HARVARD UNIV,SCH MED,MOLEC NEUROONCOL LAB,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 1994 VL 4 IS 4 BP 317 EP 318 DI 10.1111/j.1750-3639.1994.tb00914.x PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA PK299 UT WOS:A1994PK29900013 ER PT J AU LEBLANC, J GUTTENTAG, AR SHEPARD, JAO MCLOUD, TC AF LEBLANC, J GUTTENTAG, AR SHEPARD, JAO MCLOUD, TC TI IMAGING OF MEDIASTINAL FOREGUT CYSTS SO CANADIAN ASSOCIATION OF RADIOLOGISTS JOURNAL-JOURNAL DE L ASSOCIATION CANADIENNE DES RADIOLOGISTES LA English DT Article DE BRONCHOGENIC CYST; MEDIASTINUM; MAGNETIC RESONANCE IMAGING ID BRONCHOGENIC CYST; NEEDLE ASPIRATION; CT; MASSES; COMPRESSION; DIAGNOSIS; LUNG AB This study was undertaken to determine the value of magnetic resonance imaging (MRI) in the diagnosis of mediastinal foregut cysts. The MRI scans of 56 patients (with a total of 57 mediastinal masses) were reviewed. The patients (26 women and 30 men) had been examined between March 1986 and April 1991 at a tertiary-care hospital. T-1-weighted and T-2-weighted spin-echo images were available in all cases. The signal intensity of the lesions was compared with that of normal fat and muscle; the size, shape and location of the mediastinal masses were also noted. The 57 lesions consisted of 15 lymphomas, 10 neurogenic tumours, 10 thyroid masses, 6 thymomas, 6 foregut cysts and 10 other masses. Forty-eight of the masses had a signal intensity similar to that of muscle in T-1-weighted images and higher than, equal to or lower than that of fat in T-2-weighted images. Nine of the masses appeared bright in T-1-weighted images, and the signal intensity was less than or equal to that of fat. Of these, four were fore,aut cysts and five were lymphomas. Of the six foregut cysts, four had short T-1 values (the signal intensity ratio for cyst to fat ranging from 0.78 to 0.98) and long T-2 values; two had the characteristic appearance usually associated with cystic lesions containing serous fluid - long T-1 and T-2 values. All of the foregut cysts appeared to be of soft-tissue attenuation on computed tomography (CT), all were located in the middle or posterior mediastinum, and all were round or oval. Three of the cysts with high signal intensity were excised and found to contain proteinaceous or hemorrhagic fluid. The authors conclude that foregut cysts exhibit two patterns of signal intensity on MRI: long T-1 and T-2 values, a pattern characteristic of serous fluid collections; or short T-1 values (due to proteinaceous or hemorrhagic contents) and long T-2 values. MRI may contribute to the diagnosis of the latter type, which appear solid in CT scans, particularly if they are round or oval and occur in a characteristic location. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 27 TC 10 Z9 11 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA ON K1G 3Y6, CANADA SN 0846-5371 J9 CAN ASSOC RADIOL J JI Can. Assoc. Radiol. J.-J. Assoc. Can. Radiol. PD OCT PY 1994 VL 45 IS 5 BP 381 EP 386 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PJ992 UT WOS:A1994PJ99200006 PM 7922719 ER PT J AU SALGIA, R DEMETRI, GD KAPLAN, WD AF SALGIA, R DEMETRI, GD KAPLAN, WD TI CHANGES IN TC-99M RADIONUCLIDE BONE-SCAN IMAGES AND PERIPHERALIZATION OF MARROW HEMATOPOIETIC ACTIVITY ASSOCIATED WITH THE ADMINISTRATION OF GRANULOCYTE-COLONY-STIMULATING FACTOR AS AN ADJUNCT TO DOSE-INTENSIFIED CHEMOTHERAPY FOR BREAST-CANCER - A CASE-REPORT SO CANCER LA English DT Article DE GRANULOCYTE COLONY STIMULATING FACTOR; BONE SCAN; BREAST CANCER; HIGH DOSE CHEMOTHERAPY ID DRUG-THERAPY; NEUTROPENIA; CELLS AB Granulocyte colony stimulating factor (G-CSF) is used clinically for chemotherapy-associated neutropenia. Very little is known about the manner in which pharmacologic dosing of G-CSF may affect radiologic studies in vivo. Dramatic changes on bone scan associated with the administration of G-CSF used to support dose-intensified combination chemotherapy in a patient with metastatic breast carcinoma are described. The scintigraphic findings were correlated histologically with increased hematopoietic activity in the bone marrow located in peripheral bones. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT NUCL MED,BOSTON,MA 02115. RP SALGIA, R (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. NR 10 TC 5 Z9 5 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 1994 VL 74 IS 7 BP 1887 EP 1890 DI 10.1002/1097-0142(19941001)74:7<1887::AID-CNCR2820740710>3.0.CO;2-6 PG 4 WC Oncology SC Oncology GA PH625 UT WOS:A1994PH62500009 PM 7521785 ER PT J AU BERKMAN, B ROHAN, B SAMPSON, S AF BERKMAN, B ROHAN, B SAMPSON, S TI MYTHS AND BIASES RELATED TO CANCER IN THE ELDERLY SO CANCER LA English DT Article; Proceedings Paper CT National Conference on Cancer and the Older Person CY FEB 10-12, 1994 CL ATLANTA, GA DE GERIATRIC; ONCOLOGY; MYTHS; BIASES; DETECTION; SCREENING; TREATMENT ID RELAXATION RESPONSE; CARE; AGE AB Advances in medical science have led to effective treatments for cancer; however, there are myriad myths and biases related to older people and cancer that pervade both patients' and professionals' ideas on causation, course of illness, treatment, and recovery, and act as hindrances to early detection, treatment, and rehabilitation. The geriatric population is comprised of a heterogeneous group of persons who are not categorized easily according to chronologic age. Health care professionals are particularly susceptible to ageist stereotyping and negative attitudes toward the elderly because they lack training in caring for older people. In the future, the elderly will be better educated, expect greater participation in decision-making, and be less likely to postpone entry into the medical care system. There is a need to educate both health care professionals and the elderly population about the myths and realities of cancer detection and treatment. C1 HARVARD UNIV,CTR GERIATR EDUC,BOSTON,MA. RP BERKMAN, B (reprint author), MASSACHUSETTS GEN HOSP,DET SOCIAL SERV,FRUIT ST,BULFINCH 2,BOSTON,MA 02114, USA. NR 32 TC 35 Z9 35 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 1994 VL 74 IS 7 SU S BP 2004 EP 2008 DI 10.1002/1097-0142(19941001)74:7+<2004::AID-CNCR2820741703>3.0.CO;2-W PG 5 WC Oncology SC Oncology GA PJ094 UT WOS:A1994PJ09400002 PM 8087763 ER PT J AU DECKER, HJH KLAUCK, SM LAWRENCE, JB MCNEIL, J SMITH, D GEMMILL, RM SANDBERG, AA NEUMANN, HHP SIMON, B GREEN, J SEIZINGER, BR AF DECKER, HJH KLAUCK, SM LAWRENCE, JB MCNEIL, J SMITH, D GEMMILL, RM SANDBERG, AA NEUMANN, HHP SIMON, B GREEN, J SEIZINGER, BR TI CYTOGENETIC AND FLUORESCENCE IN-SITU HYBRIDIZATION STUDIES ON SPORADIC AND HEREDITARY TUMORS ASSOCIATED WITH VON HIPPEL-LINDAU SYNDROME (VHL) SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID RENAL-CELL CARCINOMA; INSITU HYBRIDIZATION; SUPPRESSOR GENE; DISEASE GENE; IDENTIFICATION; DELETION; REGION; ABNORMALITIES; POLYMORPHISMS; CHROMOSOME-3 AB We performed cytogenetic and fluorescence in situ hybridization (FISH) studies on 29 sporadic or familial tumors associated with von Hippel-Landau disease. Four of five renal cell carcinomas with detectable alterations showed clones with chromosome 3 alterations. These changes led to loss of genetic material visible with cytogenetic resolution: either an unbalanced translocation involving 3p or loss of a whole homolog 3, resulting in monosomy of 3p. We have previously mapped the VHL gene to chromosomal region 3p25-p26. We applied FISH using the single copy probes cA233 and cA479, sequences close to the VHL gene, in a search for submicroscopic deletions of 3p. Use of FISH with differentially labeled probes indicated cA479 to be distal to cA233, but both were located within bands 3p25-26. FISH with single copy probes for interphase cytogenetics detected four subclones with deletions in the VHL region in 8/22 tumors, including four tumors which appeared cytogenetically normal. FISH proved to be a powerful tool in tumor genetic studies, especially helpful in detecting tumor subclones in benign and slowly growing tumors. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,MOLEC NEUROONCOL LAB,BOSTON,MA. UNIV MASSACHUSETTS,DEPT ANAT,WORCESTER,MA 01605. WAYNE STATE UNIV,DEPT GENET,DETROIT,MI. CANC CTR SBRI,SCOTTSDALE,AZ. UNIV FREIBURG,DEPT MED,W-7800 FREIBURG,GERMANY. UNIV MARBURG,DEPT MED,W-3550 MARBURG,GERMANY. MEM UNIV NEWFOUNDLAND,CTR HLTH SCI,ST JOHNS,NF,CANADA. FU NCI NIH HHS [R0I-CA 49455, CA 20051, CA-41183] NR 37 TC 14 Z9 14 U1 0 U2 2 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 1994 VL 77 IS 1 BP 1 EP 13 DI 10.1016/0165-4608(94)90141-4 PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA PP589 UT WOS:A1994PP58900001 PM 7923076 ER PT J AU MURGUE, B TSUNEKAWA, S ROSENBERG, I DEBEAUMONT, M PODOLSKY, DK AF MURGUE, B TSUNEKAWA, S ROSENBERG, I DEBEAUMONT, M PODOLSKY, DK TI IDENTIFICATION OF A NOVEL VARIANT FORM OF FIBROBLAST GROWTH-FACTOR RECEPTOR-3 (FGFR3 IIIB) IN HUMAN COLONIC EPITHELIUM SO CANCER RESEARCH LA English DT Article ID MOLECULAR-CLONING; FAMILY; MEMBER; CELLS; GENE; SPECIFICITY; EXPRESSION; SEQUENCE; ENCODES; DOMAIN AB Although several tyrosine kinase-type growth factor receptors have been demonstrated in human colonic epithelial cells, the full spectrum of growth factor receptors has not been identified. Low stringency screening of a complementary DNA library prepared from the human colon cancer-derived cell line HT-29 with a probe containing the tyrosine kinase domain of human c-src kinase led to the identification and isolation of a clone containing a receptor class tyrosine kinase. This putative receptor was found to be identical to the human fibroblast growth factor receptor 3 (FGFR3) except for a region of 150 nucleotides (50 amino acids) encoding the presumptive ligand-binding domain, where it exhibited only 32% homology with the previously described FGFR3. The variant domain corresponded precisely to the splicing junctions of the exon encoding the carboxyl terminal half of the third immunoglobulin-like domain, suggesting that two forms of FGFR3 result from splicing of alternate exons in a manner similar to that previously found for FGFR1 and FGFR2. By prior convention, the previously reported form of FGFR3 was designated me due to its high degree of homology with the me domain of FGFR1 (83% homology) and the me domain of FGFR2 (81% homology). However, the ligand-binding domain of FGFR3 found in the HT-29 cell line was more highly divergent from all pre,iously reported FGFR immunoglobulin-like domain IIIs than any other two members of this receptor family. Therefore, me propose to designate the newly reported form as the FGFR3 IIIb variant. Genomic polymerase chain reaction confirmed that the IIIb-containing exon occupies a position 5' relative to the me-containing exon within the FGFR3 gene. Northern blot analysis using a probe encompassing sequences unique to the FGFR3 IIIb mRNA confirmed the expression of a 4.4-kilobase transcript in two colon cancer-derived cell lines as well as normal human colonic mucosa. Using a technique combining reverse transcriptase polymerase chain reaction with restriction endonuclease digestion, cell lines, primary cells, and tissues were assessed for IIIb and IIIc transcripts; expression of the IIIb variant was associated with an epithelial lineage, while the IIIc variant was expressed predominantly in nonepithelial cells and tissues. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEW ENGLAND REG PRIMATE CTR STUDY INFLAMMATORY BO,BOSTON,MA 02114. FU NIDDK NIH HHS [DK43351, DK41557] NR 42 TC 55 Z9 58 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 OCT 1 PY 1994 VL 54 IS 19 BP 5206 EP 5211 PG 6 WC Oncology SC Oncology GA PH774 UT WOS:A1994PH77400033 PM 7923141 ER PT J AU HAESSLER, R KUZUME, K CHIEN, GL WOLFF, RA DAVIS, RF VANWINKLE, DM AF HAESSLER, R KUZUME, K CHIEN, GL WOLFF, RA DAVIS, RF VANWINKLE, DM TI ANESTHETICS ALTER THE MAGNITUDE OF INFARCT LIMITATION BY ISCHEMIC PRECONDITIONING SO CARDIOVASCULAR RESEARCH LA English DT Article DE MYOCARDIAL INFARCTION; ANESTHETICS; RABBIT ID A1 ADENOSINE RECEPTORS; ISCHEMIC MYOCARDIUM; COLLATERAL FLOW; CONSCIOUS DOGS; K+ CHANNEL; SIZE; RABBIT; REPERFUSION; HALOTHANE; BLOCKADE AB Objective: The aim was to determine whether three commonly used animal anaesthetics alter the magnitude of infarct limitation achieved with ischaemic preconditioning. Methods: Eighty four anaesthetised nonpreconditioned and preconditioned open chest rabbits underwent a 30 min coronary occlusion followed by 3 h reperfusion. Ischaemic preconditioning was achieved with 5 min coronary occlusion beginning 15 min before the 30 min coronary occlusion. The anaesthetics studied were: pentobarbitone (30 mg.kg(-1) intravenously + 30-50 mg.kg(-1).h(-1) intravenously), isoflurane (1.5-2.5% end expiratory), and ketamine/xylazine (cocktail of 67 mg ketamine and 6.7 mg xylazine.ml(-1), 1 ml.kg(-1) intramuscularly + 0.3-1.3 ml.kg(-1).h(-1) intramuscularly). Area at risk was delineated with ZnCdS particles and infarction assessed with tetrazolium. Results: There were no significant differences in area at risk, heart rate, arterial pressure, and temperature between non-preconditioned and preconditioned hearts. Although infarct size was not significantly different among non-preconditioned hearts for each anaesthetic regimen (p = NS), the magnitude of infarct limitation with preconditioning varied with the anaesthetic employed (decrease in infarct size from control values of 81%, 44%, and 33% for pentobarbitone, isoflurane and ketamine/xylazine, respectively, p = 0.0145 for comparison of the three magnitudes, two factor ANOVA). Conclusion: Anaesthetic regimens affect the degree of infarct size limitation seen with ischaemic preconditioning. C1 PORTLAND VA MED CTR,DEPT ANESTHESIOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT ANESTHESIOL,PORTLAND,OR 97201. UNIV MUNICH,MUNICH,GERMANY. EHIME UNIV,MATSUYAMA,EHIME 790,JAPAN. NR 40 TC 66 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD OCT PY 1994 VL 28 IS 10 BP 1574 EP 1580 DI 10.1093/cvr/28.10.1574 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PL800 UT WOS:A1994PL80000018 PM 8001048 ER PT J AU BRADLEY, DW FRIDOVICHKEIL, JL GUDAS, JM PARDEE, AB AF BRADLEY, DW FRIDOVICHKEIL, JL GUDAS, JM PARDEE, AB TI SERUM-RESPONSIVE EXPRESSION FROM THE MURINE THYMIDINE KINASE PROMOTER IS SPECIFICALLY DISRUPTED IN A TRANSFORMED-CELL LINE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MESSENGER-RNA; STIMULATED CELLS; PROTEIN-BINDING; DNA-SEQUENCES; GENE PROMOTER; MUSCLE-CELLS; G1/S PHASE; CYCLE; GROWTH; IDENTIFICATION AB Thymidine kinase (TK) gene expression is controlled in normal cells at both the transcriptional and posttranscriptional levels. Together, these regulatory systems mediate the 20-50-fold induction of TK mRNA observed as cells traverse the G(1)-S boundary of the cell cycle. Previously, we have reported that a ''Yi'' protein complex was observed to bind the mouse TK promoter in a cell cycle-dependent manner in nontransformed cells (Q-P. Dou, J. L. Fridovich-Keil, and A. B. Pardee, Proc. Natl. Acad. Sci. USA, 88: 1157-1161, 1991) and bound constitutively in transformed cells (D. W. Bradley, Q-P. Dou, J. L. Fridovich-Keil, and A. B. Pardee, Proc. Natl. Acad. Sci. USA, 87: 9310-9314, 1990). Nonetheless, TK mRNA levels in these cells continue to exhibit a marked S-specific induction (>10 fold), raising the question: what is the status of TK promoter-mediated, as opposed to posttranscriptional, gene regulation in these transformed cells? To address this question, we have used cell synchrony experiments involving both transformed and nontransformed cells stably transfected with a TK promoter-beta-globin reporter gene construct. We have found that, in marked contrast to the tight regulation of reporter gene expression observed in nontransformed cells (J. L. Fridovich-Keil, J. M. Gudas, Q-P. Dou, I. Bouvard, and A. B. Pardee, Cell Growth and Differ., 2: 67-76, 1991), reporter gene expression in the transformed cells is constitutive and, therefore, closely parallels the presence of Yi DNA-binding activity. These data are fully consistent with other recently published observations concerning differential controls of TK transcriptional and posttranscriptional regulation (J. M. Cudas, J. L. Fridovich-Keil, and A. B. Pardee, Cell Growth and Regul., 4: 421-430, 1993) and support the hypothesis that, in transformed cells, endogenous TK is regulated predominantly at the posttranscriptional level. C1 DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. FU NIGMS NIH HHS [GM24571] NR 43 TC 2 Z9 2 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 1994 VL 5 IS 10 BP 1137 EP 1143 PG 7 WC Cell Biology SC Cell Biology GA PK595 UT WOS:A1994PK59500013 PM 7848915 ER PT J AU SILVER, MT ROSE, GA PAUL, SD ODONNELL, CJ OGARA, PT EAGLE, KA AF SILVER, MT ROSE, GA PAUL, SD ODONNELL, CJ OGARA, PT EAGLE, KA TI PREDICTING PRESERVED LEFT-VENTRICULAR EJECTION FRACTION IN PATIENTS AFTER MYOCARDIAL-INFARCTION - DERIVATION AND VALIDATION OF A SIMPLE CLINICAL RULE SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 44 EP 44 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700270 ER PT J AU GUIDRY, UA PAUL, SD VEGA, J HARRIS, C CHATURVEDI, R OGARA, PT EAGLE, KA AF GUIDRY, UA PAUL, SD VEGA, J HARRIS, C CHATURVEDI, R OGARA, PT EAGLE, KA TI THE IMPACT OF A QUALITY ASSURANCE PROGRAM ON DOOR TO NEEDLE TIME AND CHOICE OF THROMBOLYTIC AGENT IN ACUTE MYOCARDIAL-INFARCTION SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 45 EP 45 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700272 ER PT J AU MORENO, PR ABASCAL, VM PADIAL, LR BLOCK, PC DAVIDOFF, R AF MORENO, PR ABASCAL, VM PADIAL, LR BLOCK, PC DAVIDOFF, R TI GENDER DIFFERENCES IN HEMODYNAMICS AND LEFT-VENTRICULAR FUNCTION DO NOT IMPACT ON SURVIVAL AFTER PERCUTANEOUS AORTIC VALVULOPLASTY IN THE ELDERLY SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. BOSTON UNIV,MED CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 53 EP 53 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700316 ER PT J AU PAVRI, BB RUSKIN, JN BROOKS, R AF PAVRI, BB RUSKIN, JN BROOKS, R TI THE YIELD OF HEAD-UP TILT TESTING IS NOT SIGNIFICANTLY INCREASED BY REPEATING THE BASE-LINE TEST SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 53 EP 53 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700319 ER PT J AU BEYERBACH, DM WEISSMAN, NJ WEYMAN, AE AF BEYERBACH, DM WEISSMAN, NJ WEYMAN, AE TI ULTRASOUND TISSUE CHARACTERIZATION - A NEW METHOD BASED ON PRINCIPAL COMPONENTS-ANALYSIS OF ECHO FREQUENCIES SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 61 EP 61 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700360 ER PT J AU PAUL, SD EAGLE, KA KUNTZ, KM YOUNG, JR HERTZER, NR AF PAUL, SD EAGLE, KA KUNTZ, KM YOUNG, JR HERTZER, NR TI CONCORDANCE OF A VALIDATED CLINICAL RISK INDEX WITH CORONARY ANGIOGRAPHY PRIOR TO VASCULAR-SURGERY (VAS) - THE CLEVELAND CLINIC (CCF) EXPERIENCE SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CLEVELAND CLIN EDUC FDN,CLEVELAND,OH 44106. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 95 EP 95 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700544 ER PT J AU PAUL, SD BAMEZAI, V CAMBRIA, RP KOSKI, G GERTLER, JP BREWSTER, DC LAMURAGLIA, GM DAVISON, KJ TEPLICK, RS CAPASSO, V JOHNSON, S ABBOTT, WM EAGLE, KA AF PAUL, SD BAMEZAI, V CAMBRIA, RP KOSKI, G GERTLER, JP BREWSTER, DC LAMURAGLIA, GM DAVISON, KJ TEPLICK, RS CAPASSO, V JOHNSON, S ABBOTT, WM EAGLE, KA TI HIGH-INCIDENCE OF SILENT ISCHEMIA BY CONTINUOUS 12 LEAD ST-SEGMENT MONITORING AFTER VASCULAR-SURGERY - CORRELATION WITH POSTOPERATIVE PROTHROMBOTIC MILIEU SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 95 EP 95 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700542 ER PT J AU STAFFORD, R BLUMENTHAL, D AF STAFFORD, R BLUMENTHAL, D TI NATIONAL ESTIMATES OF CARDIOVASCULAR-DISEASE PREVENTION PRACTICES IN THE UNITED-STATES SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 100 EP 100 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700573 ER PT J AU STAFFORD, R BLUMENTHAL, D AF STAFFORD, R BLUMENTHAL, D TI PREDICTORS OF CHOLESTEROL SCREENING AND COUNSELING BY UNITED-STATES INTERNISTS SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 101 EP 101 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700576 ER PT J AU HOUNG, AK MAGGINI, L OEUN, S CLEMENT, CY REED, GL AF HOUNG, AK MAGGINI, L OEUN, S CLEMENT, CY REED, GL TI P-CAP-110 - A NOVEL PLATELET-CELL ACTIVATED PROTEIN SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 131 EP 131 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700739 ER PT J AU OHLIN, AK MARLAR, RA AF OHLIN, AK MARLAR, RA TI USING PCR-SSCP, A MUTATION IN THE THROMBOMODULIN GENE IS IDENTIFIED IN A 45-YEAR-OLD MALE PRESENTING WITH THROMBOEMBOLIC DISEASE SO CIRCULATION LA English DT Meeting Abstract C1 UNIV LUND HOSP,DEPT CLIN CHEM,S-22185 LUND,SWEDEN. UNIV COLORADO,SCH MED,DEPT PATHOL,DENVER,CO 80202. DENVER VET AFFAIRS MED CTR,LAB SERV,DENVER,CO. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 132 EP 132 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700742 ER PT J AU SCHWAMMENTHAL, E NAKATANI, S LEVER, HM WEYMAN, AE LEVINE, RA AF SCHWAMMENTHAL, E NAKATANI, S LEVER, HM WEYMAN, AE LEVINE, RA TI INTRAOPERATIVE TRANSESOPHAGEAL STUDIES OF THE MECHANISM OF MITRAL REGURGITATION IN HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CLEVELAND CLIN EDUC FDN,CLEVELAND,OH 44106. HEART INST,TEL HASHOMER,ISRAEL. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 170 EP 170 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700952 ER PT J AU NAKATANI, S SCHWAMMENTHAL, E LEVER, HM LYTLE, BW THOMAS, JD AF NAKATANI, S SCHWAMMENTHAL, E LEVER, HM LYTLE, BW THOMAS, JD TI INTEGRATED MECHANISM OF REDUCTION OF MITRAL SYSTOLIC ANTERIOR MOTION AFTER SEPTAL MYECTOMY IN HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY SO CIRCULATION LA English DT Meeting Abstract C1 CLEVELAND CLIN EDUC FDN,CLEVELAND,OH 44106. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 171 EP 171 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41700954 ER PT J AU AFTRING, RP TEICHER, J FALLON, JT FREEMAN, MW AF AFTRING, RP TEICHER, J FALLON, JT FREEMAN, MW TI GENE-EXPRESSION UNDER THE CONTROL OF THE SCAVENGER RECEPTOR PROMOTER IN TRANSGENIC MICE SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 190 EP 190 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701053 ER PT J AU MADSEN, JC FALLON, JT VITIELLO, D WEISSMAN, N STONE, CD SACHS, DH AF MADSEN, JC FALLON, JT VITIELLO, D WEISSMAN, N STONE, CD SACHS, DH TI CARDIAC ALLOGRAFT VASCULOPATHY IN PARTIALLY INBRED MINISWINE SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 200 EP 200 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701105 ER PT J AU LEWANDOWSKI, ED DAMICO, LA WHITE, LT YU, X AF LEWANDOWSKI, ED DAMICO, LA WHITE, LT YU, X TI CYTOSOLIC REDOX STATE INFLUENCES POSTISCHEMIC CONTRACTILE RECOVERY DURING ACTIVATION OF PYRUVATE-DEHYDROGENASE SO CIRCULATION 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 AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 210 EP 210 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701158 ER PT J AU VIVALDI, MT SAGIE, A ADAMS, MS OLIVER, A PADIAL, LR GHANDI, R WEYMAN, AE LEVINE, RA AF VIVALDI, MT SAGIE, A ADAMS, MS OLIVER, A PADIAL, LR GHANDI, R WEYMAN, AE LEVINE, RA TI 10-YEAR ECHOCARDIOGRAPHIC AND CLINICAL FOLLOW-UP OF PATIENTS WITH NONCLASSIC MITRAL-VALVE PROLAPSE - DOES IT PROGRESS SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 222 EP 222 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701226 ER PT J AU UINT, L MENDEZ, AJ AF UINT, L MENDEZ, AJ TI PROTEIN-KINASE-C DOWN-REGULATION INHIBITS CHOLESTEROL EFFLUX MEDIATED BY APOLIPOPROTEIN-A-I BUT NOT BY HIGH-DENSITY-LIPOPROTEIN IN CULTURED-CELLS SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 240 EP 240 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701325 ER PT J AU SEMIGRAN, GE TRUDEAU, NR MCCARTHY, M GARCIA, M LARAIA, PJ SEMIGRAN, MJ BOUCHER, CA AF SEMIGRAN, GE TRUDEAU, NR MCCARTHY, M GARCIA, M LARAIA, PJ SEMIGRAN, MJ BOUCHER, CA TI ROUTINE THALLIUM IMAGING DOES NOT ADD PROGNOSTIC INFORMATION TO EXERCISE TESTING IN WOMEN WITH AN ABNORMAL REST ECG SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SPAULDING REHABIL HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 273 EP 273 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701503 ER PT J AU BLOCH, KD GOLDFELD, AE AF BLOCH, KD GOLDFELD, AE TI INFECTION BY SENDAI VIRUS INDUCES ENDOTHELIN-1 GENE-EXPRESSION IN HUMAN MONOCYTES AND MONOCYTOID CELL-LINES SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 293 EP 293 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701608 ER PT J AU POMBO, CM KYRIAKIS, JM BONVENTRE, JV FORCE, TL AF POMBO, CM KYRIAKIS, JM BONVENTRE, JV FORCE, TL TI THE P54 STRESS-ACTIVATED PROTEIN-KINASES (SAPKS) ARE MAJOR C-JUN AMINO-TERMINAL KINASES ACTIVATED BY ISCHEMIA AND REPERFUSION SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 303 EP 303 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701662 ER PT J AU LEE, MY JIANG, L HANDSCHUMACHER, MD GUERRERO, JL DERMAN, RM KRAUSS, M VLAHAKES, GJ LEVINE, RA AF LEE, MY JIANG, L HANDSCHUMACHER, MD GUERRERO, JL DERMAN, RM KRAUSS, M VLAHAKES, GJ LEVINE, RA TI 3-DIMENSIONAL VOXEL IMAGING OF THE LEFT-VENTRICLE - IS IT QUANTITATIVELY ACCURATE - IN-VIVO VALIDATION SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 337 EP 337 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701844 ER PT J AU MELE, D PRATOLA, C PEDINI, I ALBONI, P LEVINE, RA AF MELE, D PRATOLA, C PEDINI, I ALBONI, P LEVINE, RA TI VALIDATION AND APPLICATION IN PATIENTS OF A NEW SYSTEM FOR 3-DIMENSIONAL ECHOCARDIOGRAPHIC RECONSTRUCTION OF THE LEFT-VENTRICLE SO CIRCULATION LA English DT Meeting Abstract C1 OSPED CIVILE,CENTO,ITALY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 337 EP 337 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701845 ER PT J AU HANDSCHUMACHER, MD JIANG, L LEE, MY WILLIAMS, MJA SVIZZERO, T LEVINE, RA AF HANDSCHUMACHER, MD JIANG, L LEE, MY WILLIAMS, MJA SVIZZERO, T LEVINE, RA TI ACCURACY OF 3-DIMENSIONAL ECHOCARDIOGRAPHIC RECONSTRUCTION BY ELECTROMAGNETIC POSITIONAL LOCATION - IN-VIVO VALIDATION FOR RIGHT-VENTRICULAR VOLUME SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Michael, Williams/C-1759-2008 OI Michael, Williams/0000-0003-4822-4962 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 338 EP 338 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701852 ER PT J AU JIANG, L LEE, MY GUERRERO, JL HANDSCHUMACHER, MD ADAMS, MS DERMAN, RM KRAUSS, M WEYMAN, AE LEVINE, RA AF JIANG, L LEE, MY GUERRERO, JL HANDSCHUMACHER, MD ADAMS, MS DERMAN, RM KRAUSS, M WEYMAN, AE LEVINE, RA TI CAN 3-DIMENSIONAL VOXEL IMAGES WITH A ROTATING TRANSDUCER BE APPLIED TO THE RIGHT VENTRICLE - IN-VIVO STUDY SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 338 EP 338 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41701851 ER PT J AU CHEN, CG GILLAM, LD KNIPP, DR BOW, LM LI, L CHEN, LL MCKAY, RG FALLON, JT WATERS, DD AF CHEN, CG GILLAM, LD KNIPP, DR BOW, LM LI, L CHEN, LL MCKAY, RG FALLON, JT WATERS, DD TI A PORCINE MODEL OF MYOCARDIAL HIBERNATION - METABOLIC AND STRUCTURAL ADAPTATIONS SO CIRCULATION LA English DT Meeting Abstract C1 HARTFORD HOSP,HARTFORD,CT 06115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 369 EP 369 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702020 ER PT J AU MORENO, PR FALK, E FUSTER, V FALLON, JT AF MORENO, PR FALK, E FUSTER, V FALLON, JT TI INCREASED MACROPHAGE CONTENT OF RESTENOTIC CORONARY PLAQUE TISSUE SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 3 Z9 3 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 OCT PY 1994 VL 90 IS 4 BP 378 EP 378 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702069 ER PT J AU WILLIAMS, MJA DOW, CJ WEYMAN, AE PICARD, MH AF WILLIAMS, MJA DOW, CJ WEYMAN, AE PICARD, MH TI MYOCARDIAL DYSFUNCTION AFTER ROTATIONAL CORONARY ATHERECTOMY - SERIAL EVALUATION BY ECHOCARDIOGRAPHY SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Michael, Williams/C-1759-2008 OI Michael, Williams/0000-0003-4822-4962 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 393 EP 393 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702151 ER PT J AU BLOCH, KD WOLFRAM, JR ROBERTS, JD LEPORE, JJ FILIPPOV, G BROWN, DM JACOB, HJ BLOCH, DB AF BLOCH, KD WOLFRAM, JR ROBERTS, JD LEPORE, JJ FILIPPOV, G BROWN, DM JACOB, HJ BLOCH, DB TI EVIDENCE FOR THE EXISTENCE OF A 2ND INDUCIBLE NOS GENE SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 407 EP 407 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702220 ER PT J AU ALBERT, CM MCGOVERN, BA RUSKIN, JN AF ALBERT, CM MCGOVERN, BA RUSKIN, JN TI GENDER DIFFERENCES IN CARDIAC-ARREST SURVIVORS SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 455 EP 455 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702475 ER PT J AU BILLMAN, GE LEAF, A AF BILLMAN, GE LEAF, A TI EFFECT OF OMEGA-3-FATTY-ACIDS ON SUSCEPTIBILITY TO SUDDEN-DEATH - PROTECTION FROM VENTRICULAR-FIBRILLATION DURING MYOCARDIAL-ISCHEMIA SO CIRCULATION LA English DT Meeting Abstract C1 OHIO STATE UNIV,COLUMBUS,OH 43210. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 466 EP 466 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702538 ER PT J AU YU, X DAMICO, LA WHITE, LT LEWANDOWSKI, ED AF YU, X DAMICO, LA WHITE, LT LEWANDOWSKI, ED TI CARBON INFLUX EFFLUX FROM THE TCA CYCLE ADJUSTS TO CHANGES IN WORKLOAD AND METABOLIC FLUX AS SHOWN BY DYNAMIC C-13 NMR OF INTACT HEARTS SO CIRCULATION 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 AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 468 EP 468 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702551 ER PT J AU JIANG, L WEISSMAN, NJ LEVANGIE, MW HE, J SVIZZERO, T PICARD, MH AF JIANG, L WEISSMAN, NJ LEVANGIE, MW HE, J SVIZZERO, T PICARD, MH TI PERCUTANEOUS TRANSVENOUS INTRACARDIAC ULTRASOUND IMAGING - A NEW APPROACH TO MONITOR LEFT-VENTRICULAR FUNCTION SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 494 EP 494 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702693 ER PT J AU CHEN, MH DEPRADA, JAV PADIAL, L WEYMAN, AE CHEN, CG AF CHEN, MH DEPRADA, JAV PADIAL, L WEYMAN, AE CHEN, CG TI INTRACARDIAC ULTRASOUND IS MORE ACCURATE THAN BIPLANE ANGIOGRAPHY IN THE MEASUREMENT OF RV VOLUME SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARTFORD HOSP,HARTFORD,CT 06115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 495 EP 495 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702699 ER PT J AU DEPRADA, JAV CHEN, MH PADIAL, L SHEHATA, A GILLAM, LD CHEN, CG AF DEPRADA, JAV CHEN, MH PADIAL, L SHEHATA, A GILLAM, LD CHEN, CG TI INTRACARDIAC ULTRASOUND MEASUREMENT OF NORMAL AND AKINETIC ENDOCARDIAL SURFACES BY RECONSTRUCTING SEQUENTIAL LEFT-VENTRICULAR CROSS-SECTIONS SO CIRCULATION LA English DT Meeting Abstract C1 HARTFORD HOSP,HARTFORD,CT 06115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 495 EP 495 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41702694 ER PT J AU UTANS, U ARCECI, RJ YAMASHITA, Y BIANCHI, C RUSSELL, ME AF UTANS, U ARCECI, RJ YAMASHITA, Y BIANCHI, C RUSSELL, ME TI UP-REGULATION OF A NOVEL MACROPHAGE GENE, ALLOGRAFT INFLAMMATORY FACTOR-I, IN RAT MODELS OF CHRONIC CARDIAC REJECTION AND BALLOON INJURY OF THE CAROTID-ARTERY SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 572 EP 572 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703113 ER PT J AU PICARD, MH BOSCH, HG MORRISSEY, RL REIBER, JHC AF PICARD, MH BOSCH, HG MORRISSEY, RL REIBER, JHC TI AUTOMATED ECHOCARDIOGRAPHIC VENTRICULAR VOLUME QUANTITATION - VALIDATION OF A NEW BORDER DETECTION METHOD SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. LEIDEN UNIV HOSP,2333 AA LEIDEN,NETHERLANDS. RI Bosch, Johan/E-4280-2014 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 608 EP 608 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703308 ER PT J AU MORENO, PR KUSHWAHA, SS FUSTER, V COCKRILL, BA KACMARECK, R ZAPOL, WM FIFER, MA DEC, GW SEMIGRAN, MMJ AF MORENO, PR KUSHWAHA, SS FUSTER, V COCKRILL, BA KACMARECK, R ZAPOL, WM FIFER, MA DEC, GW SEMIGRAN, MMJ TI DIRECT MYOCARDIAL EFFECTS OF INHALED NITRIC-OXIDE IN HEART-FAILURE SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 1 Z9 1 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 OCT PY 1994 VL 90 IS 4 BP 609 EP 609 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703316 ER PT J AU ROSE, GA KUSHWAHA, SS SEMIGRAN, MJ DINSMORE, RE FIFER, MA AF ROSE, GA KUSHWAHA, SS SEMIGRAN, MJ DINSMORE, RE FIFER, MA TI ADENOSINE INCREASES PULMONARY CAPILLARY WEDGE PRESSURE BY A CARDIAC, NOT A PERIPHERAL, EFFECT SO CIRCULATION 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 AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 609 EP 609 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703315 ER PT J AU SWEENEY, MO GUY, M MCGOVERN, BA GARAN, H RUSKIN, JN AF SWEENEY, MO GUY, M MCGOVERN, BA GARAN, H RUSKIN, JN TI SUDDEN CARDIAC DEATH IN PATIENTS WITH 3 GENERATION IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS - RELATIONSHIP TO CLINICAL-VARIABLES, LEAD CONFIGURATION, AND SPONTANEOUS VENTRICULAR ARRHYTHMIA THERAPIES SO CIRCULATION LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 654 EP 654 PN 2 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PN417 UT WOS:A1994PN41703549 ER PT J AU SAGER, PT FOLLMER, C UPPAL, P PRUITT, C GODFREY, R AF SAGER, PT FOLLMER, C UPPAL, P PRUITT, C GODFREY, R TI THE EFFECTS OF BETA-ADRENERGIC STIMULATION ON THE FREQUENCY-DEPENDENT ELECTROPHYSIOLOGIC ACTIONS OF AMIODARONE AND SEMATILIDE IN HUMANS SO CIRCULATION LA English DT Article DE AMIODARONE; SEMATILIDE; ACTION POTENTIAL DURATION; ISOPROTERENOL ID ACTION-POTENTIAL DURATION; TRANSIENT OUTWARD CURRENT; III ANTIARRHYTHMIC AGENT; RECTIFIER K+-CURRENT; VENTRICULAR-TACHYCARDIA; MYOCARDIAL-INFARCTION; REFRACTORY PERIOD; SODIUM CURRENT; GUINEA-PIG; ISOPROTERENOL AB Background The autonomic nervous system appears to play an important role in the development of clinical ventricular arrhythmias, and beta-adrenergic sympathetic stimulation may be important in modulating the electrophysiologic effects of class III antiarrhythmic agents. This study prospectively determined the effects of isoproterenol on the frequency-dependent actions of sematilide (a pure class III agent that selectively blocks the delayed rectifier potassium current) and amiodarone (a class III agent with a complex pharmacologic profile) on ventricular repolarization, refractoriness, and conduction. Methods and Results The frequency-dependent electrophysiologic effects of sematilide (n=11) and amiodarone (n=22) were determined at (1) drug-free baseline, (2) during steady state (>48 hours) dosing with sematilide (455+/-5 mg/d [mean+/-SEM]) or after 10.5 days of amiodarone loading (1618+/-32 mg/d), and (3) during isoproterenol administration (35 ng/kg per minute) to patients receiving sematilide or amiodarone. Electrophysiologic determinations were made at paced cycle lengths of 300 to 500 ms. The two groups were similar in all clinical characteristics. The ventricular action potential duration at 90% repolarization (APD(90)) was significantly prolonged by sematilide (mean increase, 7+/-1%, P<.01 by ANOVA) and amiodarone (mean increase, 12+/-1%, P<.001). However, while sematilide-induced APD(90) prolongation was fully reversed to baseline values during isoproterenol infusion, the APD(90) in patients receiving amiodarone remained significantly prolonged by a mean of 6+/-1% compared with baseline (P=.005). The reduction in the APD(90) was frequency dependent for both agents, with a greater reduction at longer than shorter paced cycle lengths (P<.02). During isoproterenol infusion the right ventricular effective refractory period (RVERP) in patients receiving sematilide was significantly reduced to mean values of 8+/-2% below baseline (P<.05), whereas the RVERP in patients receiving amiodarone remained significantly prolonged by a mean of 7+/-1% above baseline values (P=.01). Sematilide and sematilide/isoproterenol had no effect on ventricular conduction. Amiodarone increased the QRS duration by 14+/-4% (paced cycle length, 500 ms) to 32+/-5% (paced cycle length, 300 ms) compared with baseline values. Isoproterenol attenuated amiodarone-induced QRS prolongation by a mean of 5+/-1% (P=.005), without frequency-dependent effects, consistent with isoproterenol-induced increases in the sodium current. During isoproterenol infusion there was a trend for the sustained VT cycle length to be reduced below baseline in patients receiving sematilide (275+/-16 versus 298+/-55 ms, P=.06), whereas it remained significantly prolonged compared with baseline in patients receiving amiodarone (327+/-17 versus 257+/-12 ms, P<.001). Conclusions Isoproterenol fully reversed the effects of selective potassium channel block with sematilide on the APD(90) and further reduced the RVERP to values significantly below baseline; it partially attenuated but did not fully reverse amiodarone-induced prolongation of the APD(90) and RVERP, which remained significantly prolonged beyond baseline values. Isoproterenol exerted frequency-dependent effects in both patient groups on the APD(90); it modestly attenuated amiodarone-induced conduction slowing without frequency-dependent actions; and the sustained VT cycle length remained significantly prolonged during isoproterenol administration to patients receiving amiodarone but not in those receiving sematilide. These findings may have important clinical implications regarding protection from arrhythmia development in patients receiving pure class III agents or amiodarone. C1 UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA USA. RP SAGER, PT (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, DIV CARDIOL, 691-W111E, WILSHIRE & SAWTELLE BLVD, LOS ANGELES, CA 90073 USA. NR 56 TC 42 Z9 43 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 1811 EP 1819 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PM632 UT WOS:A1994PM63200026 PM 7923666 ER PT J AU BODE, C HUDELMAYER, M MEHWALD, P BAUER, S FREITAG, M VONHODENBERG, E NEWELL, JB KUBLER, W HABER, E RUNGE, MS AF BODE, C HUDELMAYER, M MEHWALD, P BAUER, S FREITAG, M VONHODENBERG, E NEWELL, JB KUBLER, W HABER, E RUNGE, MS TI FIBRIN-TARGETED RECOMBINANT HIRUDIN INHIBITS FIBRIN DEPOSITION ON EXPERIMENTAL CLOTS MORE EFFICIENTLY THAN RECOMBINANT HIRUDIN SO CIRCULATION LA English DT Article DE PHARMACOLOGY; ANTICOAGULANTS; THROMBOSIS ID TISSUE PLASMINOGEN-ACTIVATOR; ACUTE MYOCARDIAL-INFARCTION; CORONARY THROMBOLYSIS; HEPARIN-ANTITHROMBIN; THROMBIN; INVIVO; REOCCLUSION; CONJUGATION; UROKINASE; POTENCY AB Background Although the indirect thrombin inhibitor heparin and the more potent direct inhibitor hirudin are useful in Preventing thrombosis, a substantial opportunity remains for improving the thrombus selectivity of thrombin inhibitors. Methods and Results To explore the effect of targeting an antithrombin to the surface of a clot, we covalently linked recombinant hirudin to the Fab' (or IgG) of a monoclonal antibody (59D8) that selectively binds to an epitope on fibrin that becomes exposed only after thrombin cleaves fibrinopeptide B. Antibody-coupled hirudin bound to an immobilized peptide of the fibrin beta-chain amino-terminal sequence and inhibited the peptidolytic activity of thrombin more efficiently than free hirudin. Thrombin inhibition dependent on binding to immobilized fibrin monomer was enhanced 1100-fold (P<.0001). Hirudin-59D8 Fab' was 10 times more effective than hirudin in inhibiting fibrin deposition on experimental clot surfaces in fibrinogen solution (P<.0001) and human plasma (P<.0001). The more effective inhibition of thrombin by the conjugate was supported by significantly diminished concentrations of fibrinopeptide A in the plasma supernatant of the clot (P=.0001). Inhibition of clotting by an uncoupled mixture of hirudin and 59D8 Fab' was indistinguishable from that by hirudin alone, indicating that the conjugate's greater inhibitory activity was due to the covalent linkage between antibody and hirudin. Conclusions Fibrin-targeted hirudin (in comparison with unmodified hirudin) significantly reduces fibrin deposition on the surface of experimental clots. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNIV TEXAS,MED BRANCH,DIV CARDIOL,GALVESTON,TX. RP BODE, C (reprint author), UNIV HEIDELBERG,MED KLIN KARDIOL 3,BERGHEIMERSTR 58,D-69115 HEIDELBERG,GERMANY. NR 27 TC 43 Z9 44 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT PY 1994 VL 90 IS 4 BP 1956 EP 1963 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PM632 UT WOS:A1994PM63200045 PM 7923685 ER PT J AU GAA, J LEE, MJ SAINI, S AF GAA, J LEE, MJ SAINI, S TI CASE-REPORT - HEMORRHAGIC HEPATIC ADENOMA - MR FEATURES SO CLINICAL RADIOLOGY LA English DT Note ID FOCAL NODULAR HYPERPLASIA; APPEARANCE; DIAGNOSIS; TUMORS AB Hepatic adenomas are incidentally detected with increasing frequency after imaging the abdomen for unrelated pathology. We report the CT and MR features of an asymptomatic hepatic adenoma with evidence of subclinical intratumoral haemorrhage. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 8 TC 2 Z9 2 U1 0 U2 0 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 1994 VL 49 IS 10 BP 719 EP 720 DI 10.1016/S0009-9260(05)82669-8 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PL405 UT WOS:A1994PL40500016 PM 7955837 ER PT J AU DISALVO, T MATHIER, M MCNAMARA, D SEMIGRAN, M DEC, GW AF DISALVO, T MATHIER, M MCNAMARA, D SEMIGRAN, M DEC, GW TI PERCENT PREDICTED HEART-RATE MAXIMUM ACHIEVED DURING CARDIOPULMONARY EXERCISE TESTING PREDICTS FUNCTIONAL-CAPACITY IN ADVANCED HEART-FAILURE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1994 VL 42 IS 3 BP A455 EP A455 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PD505 UT WOS:A1994PD50500561 ER PT J AU DISALVO, T MATHIER, M MCNAMARA, D SEMIGRAN, M DEC, GW AF DISALVO, T MATHIER, M MCNAMARA, D SEMIGRAN, M DEC, GW TI VENTRICULAR EJECTION FRACTION DISCORDANCE PREDICTS BETTER FUNCTIONAL-CAPACITY AND DECREASED MORTALITY IN ADVANCED HEART-FAILURE SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1994 VL 42 IS 3 BP A445 EP A445 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PD505 UT WOS:A1994PD50500509 ER PT J AU THET, LA ALLEN, PL KUCKEN, AM KAYSEN, JH AF THET, LA ALLEN, PL KUCKEN, AM KAYSEN, JH TI CHANGES IN THYROID TRANSCRIPTION FACTOR-I GENE-EXPRESSION DURING LUNG DEVELOPMENT SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD OCT PY 1994 VL 42 IS 3 BP A427 EP A427 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PD505 UT WOS:A1994PD50500440 ER PT J AU YAREMCHUK, MJ AF YAREMCHUK, MJ TI EXPERIMENTAL STUDIES ADDRESSING RIGID FIXATION IN CRANIOFACIAL SURGERY SO CLINICS IN PLASTIC SURGERY LA English DT Article AB The large clinical experience with plates and screws has made the surgeon aware of unpredicted biologic and clinical implications of these devices outside their ability to maintain bone position. This article presents recent experimental data on these issues, including potential growth alteration, effects on volume persistence of onlay grafts, artifacts produced during CT and MR imaging, and the potential for bioresorbable fixation systems. RP YAREMCHUK, MJ (reprint author), MASSACHUSETTS GEN HOSP,WACC,SUITE 453,BOSTON,MA 02114, USA. NR 0 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0094-1298 J9 CLIN PLAST SURG JI Clin. Plast. Surg. PD OCT PY 1994 VL 21 IS 4 BP 517 EP 524 PG 8 WC Surgery SC Surgery GA PN350 UT WOS:A1994PN35000005 PM 7813152 ER PT J AU HEILIGENHAUS, A BERRA, A FOSTER, CS AF HEILIGENHAUS, A BERRA, A FOSTER, CS TI CD4+V-BETA-8+ T CELLS MEDIATE HERPES STROMAL KERATITIS SO CURRENT EYE RESEARCH LA English DT Article DE T CELL RECEPTOR; KERATITIS; HERPES SIMPLEX VIRUS TYPE I; MOUSE ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; SIMPLEX VIRUS; RECEPTOR REPERTOIRE; IMPARTS REACTIVITY; CORNEAL INFECTION; MICE; ANTIBODY; DISEASE; SEGMENT; ANTIGEN AB T lymphocytes are critical in mediating herpes simplex stromal keratitis (HSK). Using immunohistologic methods, we studied the T cell subsets and the T cell receptor variable region (TCR V beta) repertoire of T cells in the eye after corneal infection with HSV (KOS strain). We investigated the possibility that there might be differential V beta preferential usage in HSK resistant and susceptible BALB/c congenic mice that differ only in a small region associated with the Igh-1 gene locus. The inflamed corneas of HSK susceptible C.AL-20 mice were mainly infiltrated by CD4+ cells and by V beta 8 expressing cells. Such T cells were not seen in the corneas of resistant C.B-17 mice. Our results indicate that CD4+V beta 8+ cells are involved in mediating HSV-1 stromal keratitis. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA 02114. UNIV ESSEN GESAMTHSCH,DEPT OPHTHALMOL,ESSEN,GERMANY. FU NEI NIH HHS [EY-06008] NR 34 TC 9 Z9 12 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 OCT PY 1994 VL 13 IS 10 BP 711 EP 716 DI 10.3109/02713689409047004 PG 6 WC Ophthalmology SC Ophthalmology GA PL804 UT WOS:A1994PL80400001 PM 7842719 ER PT J AU BOUSSIOTIS, VA GRIBBEN, JG FREEMAN, GJ NADLER, LM AF BOUSSIOTIS, VA GRIBBEN, JG FREEMAN, GJ NADLER, LM TI BLOCKADE OF THE CD28 COSTIMULATORY PATHWAY - A MEANS TO INDUCE TOLERANCE SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL ACTIVATION; ANTIGEN-PRESENTING CELLS; CTLA-4 COUNTER-RECEPTOR; LYMPHOCYTES-T; CLONAL ANERGY; B-CELLS; CARDIAC ALLOGRAFT; ADDITIONAL LIGAND; B7/BB1 ANTIGEN; EXPRESSION AB Presentation of antigen to the T-cell receptor (TCR) without co-stimulation results in a state of antigen-specific unresponsiveness on rechallenge, known as anergy in vitro and tolerance in vivo. Mounting evidence suggests that inhibition of the B7-CD28 co-stimulatory pathway is both necessary and sufficient to induce antigen-specific T-cell anergy. Anergy is not static because specific signals are required to maintain this state and prevent its reversal. Attention to these issues will be critical to translate these basic studies to the clinical arenas of transplantation, tumor immunity and autoimmunity. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP BOUSSIOTIS, VA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,ROOM 740,44 BINNEY ST,BOSTON,MA 02115, USA. NR 80 TC 136 Z9 137 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 1994 VL 6 IS 5 BP 797 EP 807 DI 10.1016/0952-7915(94)90087-6 PG 11 WC Immunology SC Immunology GA PM735 UT WOS:A1994PM73500018 PM 7530013 ER PT J AU PEGUES, DA MILLER, SI AF PEGUES, DA MILLER, SI TI SALMONELLOSIS, INCLUDING TYPHOID-FEVER SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Article AB Salmonella spp. are a major cause of human morbidity and mortality. The increased frequency of egg-associated Salmonella enteritidis outbreaks emphasizes the need for new prevention and control strategies. With the emergence of multidrug-resistant Salmonella strains, third-generation cephalosporins and quinolones are increasingly necessary to treat both complicated non-typhoidal Salmonella infections and typhoid fever. However, resistance is now being reported to both classes of antimicrobial agents, and there is unresolved concern about the use of quinolones in children aged less than 10 years. Recent studies of Salmonella pathogenesis and interactions with epithelial cells and macrophages have increased our understanding of Salmonella spp. infection. Interest also has been generated by the development of virulence-attenuated Salmonella typhi strains as new oral vaccines and as multivalent-vaccine vectors to express heterologous antigens to protect against a variety of infectious diseases. RP PEGUES, DA (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,INFECT DIS UNIT,GRAY 5,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 14 Z9 14 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD OCT PY 1994 VL 7 IS 5 BP 616 EP 623 DI 10.1097/00001432-199410000-00016 PG 8 WC Infectious Diseases SC Infectious Diseases GA PN232 UT WOS:A1994PN23200016 ER PT J AU POLONSKY, WH APONTE, JE ANDERSON, BJ JACOBSON, AM LOHRER, PA COLE, CF AF POLONSKY, WH APONTE, JE ANDERSON, BJ JACOBSON, AM LOHRER, PA COLE, CF TI INSULIN OMISSION IN WOMEN WITH IDDM SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; EATING DISORDERS; YOUNG-WOMEN AB OBJECTIVE- To describe the extent of intentional insulin omission in an outpatient population of women with insulin-dependent diabetes mellitus (IDDM) and examine its relationship to disordered eating, attitudes toward diabetes, other psychosocial factors, long-term complications, and glycemic control. RESEARCH DESIGN AND METHODS- Before their routinely scheduled clinic appointments, female IDDM patients who were 13-60 years of age completed a self-report survey (final n = 341). The survey included standardized questionnaires assessing disordered eating altitudes and behaviors, psychological functioning (general distress, diabetes-specific distress, and hypoglycemic fear), attitudes toward diabetes, and self-care behaviors. All subjects were assessed for glycosylated hemoglobin within 30 days of survey completion. Long-term complications were determined through chart review. RESULTS- Approximately 31% of the subject sample, representing women of all ages, reported intentional insulin omission, but only 8.8% reported frequent omission. Compared with non-emitters, emitters reported more disordered eating, greater psychological distress (general and diabetes-specific), more hypoglycemic fear, poorer regimen adherence, and greater fears concerning improved diabetes management (which may lead to weight gain). Omitters evidenced poorer glycemic control, more diabetes-related hospitalizations, and higher rates of retinopathy and neuropathy. Multivariate examination revealed only two variables that independently predicted omission: diabetes-specific distress and fear of improved glycemic control (''because I will gain weight''). Of the omitters, approximately half reported omitting insulin for weight-management purposes (weight-related omitters). These subjects evidenced significantly greater psychological distress, poorer regimen adherence (including more frequent omission), poorer glycemic control, and higher rates of complications than did non-weight-related emitters as well as non-emitters. Non-weight-related emitters tended to fall between weight-related omitters and non-emitters on most measures of psychological functioning, adherence, and CONCLUSIONS- These findings suggest that insulin omission is common, that it is not limited to younger women, and that the medical consequences of omission, especially frequent omission, may be severe. Although a strong association between omission and disordered eating was observed, these data suggest that this link may be complicated by important diabetes-specific factors. Patients preoccupied with eating and weight concerns may also become emotionally overwhelmed by diabetes and/or fearful of normoglycemia (and the associated weight related consequences), thus reinforcing the desire to omit insulin and maintain elevated blood glucose levels. C1 JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. NR 22 TC 149 Z9 154 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1994 VL 17 IS 10 BP 1178 EP 1185 DI 10.2337/diacare.17.10.1178 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PJ311 UT WOS:A1994PJ31100013 PM 7821139 ER PT J AU NATHAN, DM AF NATHAN, DM TI REVISION OF IMPROVED MEAN GLYCEMIA FROM HBA(1C) - REPLY SO DIABETES CARE LA English DT Letter ID GLYCOSYLATED HEMOGLOBIN RP NATHAN, DM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIABET UNIT,BOSTON,MA 02114, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 1994 VL 17 IS 10 BP 1228 EP 1229 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PJ311 UT WOS:A1994PJ31100033 ER PT J AU SMITH, FE BONNERWEIR, S LEAHY, JL LAUFGRABEN, MJ OGAWA, Y ROSEN, KM VILLAKOMAROFF, L AF SMITH, FE BONNERWEIR, S LEAHY, JL LAUFGRABEN, MJ OGAWA, Y ROSEN, KM VILLAKOMAROFF, L TI PANCREATIC REG/PANCREATIC STONE PROTEIN (PSP) GENE-EXPRESSION DOES NOT CORRELATE WITH BETA-CELL GROWTH AND REGENERATION IN RATS SO DIABETOLOGIA LA English DT Article DE PANCREAS; GROWTH FACTORS; GENE EXPRESSION; BETA CELLS ID REG GENE; NUCLEOTIDE-SEQUENCE; SECRETORY PROTEIN; EXOCRINE; INSULIN; ISLETS; TISSUE; FORMS; RNA AB The Reg/pancreatic stone protein (PSP) gene is postulated to be an important regulator of pancreatic beta-cell growth. To investigate this hypothesis, we analysed the expression of the Reg/PSP gene following a 90% pancreatectomy and after chronic glucose infusion, two well-defined models of pancreatic beta-cell growth. There was a rapid induction of the Reg/PSP gene in the remnant pancreas after a 90% pancreatectomy in rats during the period of marked growth of the exocrine and islet tissue. However, a similar rapid, but smaller, induction of the Reg/PSP gene was observed in sham-operated rats and in non-surgical control rats in which there was no enhanced pancreatic growth. Furthermore, there was no pancreatic Reg/PSP gene induction in a model of selective beta-cell growth, the chronic glucose-infused rat. Thus, it is unlikely that: Reg/PSP is a beta-cell specific growth factor, even though the function of this important pancreatic gene is still unknown. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV NEUROSCI,BOSTON,MA 02115. RP SMITH, FE (reprint author), JOSLIN DIABET CTR,DIV RES,ISLET TRANSPLANTAT & CELL BIOL SECT,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK 36836, DK 44523, DK 35449] NR 26 TC 24 Z9 25 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1994 VL 37 IS 10 BP 994 EP 999 DI 10.1007/BF00400462 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PJ310 UT WOS:A1994PJ31000005 PM 7851694 ER PT J AU DELPRATO, S LEONETTI, E SIMONSON, DC SHEEHAN, P MATSUDA, M DEFRONZO, RA AF DELPRATO, S LEONETTI, E SIMONSON, DC SHEEHAN, P MATSUDA, M DEFRONZO, RA TI EFFECT OF SUSTAINED PHYSIOLOGICAL HYPERINSULINEMIA AND HYPERGLYCEMIA ON INSULIN-SECRETION AND INSULIN SENSITIVITY IN MAN SO DIABETOLOGIA LA English DT Article DE CHRONIC HYPERINSULINEMIA; CHRONIC HYPERGLYCEMIA; INSULIN RESISTANCE; INSULIN SECRETION; IMPAIRED GLYCOGEN SYNTHESIS ID IMPAIRED GLUCOSE-TOLERANCE; INDIRECT CALORIMETRY; NATURAL-HISTORY; ADIPOSE-CELLS; DIABETIC RATS; PIMA-INDIANS; BETA-CELL; RESISTANCE; NIDDM; DISEASE AB Two study protocols to examine the effects of chronic (72-96 h) physiologic euglycaemic hyperinsulinaemia (+ 72 pmol/l) and chronic hyperglycaemic (+ 1.4 mmol/l) hyperinsulinaemia (+ 78 pmol/l) on insulin sensitivity and insulin secretion were performed in 15 healthy young subjects. Subjects received a three-step euglycaemic insulin (insulin infusion rates = 1.5, 3, and 6 nmol.kg(-1).min(-1)) clamp and a hyperglycaemia (6.9 mmol/l) clamp before and after chronic insulin or glucose infusion. Following 4 days of sustained euglycaemic hyperinsulinaemia whole body glucose disposal decreased by 20-40%. During each insulin clamp step, the defect in insulin action was accounted for by impaired non-oxidative glucose disposal (p < 0.01). Chronic euglycaemic hyperinsulinaemia did not alter insulin-mediated suppression of hepatic glucose production. Following insulin infusion the ability of hyperglycaemia to stimulate insulin secretion was significantly diminished. Following 72 h of chronic glucose infusion (combined hyperglycaemic hyperinsulinaemia), there was no change in whole body glucose disposal. However, glucose oxidation during each insulin clamp step was significantly increased and there was a reciprocal decline in non-oxidative glucose disposal by 25-39% (p < 0.01); suppression of hepatic glucose production by insulin was unaltered by chronic hyperglycaemic hyperinsulinaemia. Chronic glucose infusion increased the plasma insulin response to acute hyperglycaemia more than twofold. These results demonstrate that chronic, physiologic hyperinsulinaemia, whether created by exogenous insulin infusion or by stimulation of endogenous insulin secretion, leads to the development of insulin resistance, which is characterized by a specific defect in the non-oxidative (glycogen synthetic) pathway. These findings indicate that hyperinsulinaemia should be considered, not only as a compensatory response to insulin resistance, but also as a self-perpetuating cause of the defect in insulin action. C1 UNIV TEXAS,HLTH SCI CTR,DIV DIABET,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. UNIV PADUA,CATTEDRA MALATTIE RICAMBIO,PADUA,ITALY. BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RI Del Prato, Stefano/K-3405-2016; OI Del Prato, Stefano/0000-0002-5388-0270; Matsuda, Masafumi/0000-0001-8543-1616 FU NCRR NIH HHS [M01-RR-01346]; NIA NIH HHS [AG00233]; NIADDK NIH HHS [AM24092] NR 46 TC 177 Z9 179 U1 1 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 1994 VL 37 IS 10 BP 1025 EP 1035 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PJ310 UT WOS:A1994PJ31000009 PM 7851681 ER PT J AU HARMS, BA MYERS, GA ROSENFELD, DJ STARLING, JR AF HARMS, BA MYERS, GA ROSENFELD, DJ STARLING, JR TI MANAGEMENT OF FULMINANT ULCERATIVE-COLITIS BY PRIMARY RESTORATIVE PROCTOCOLECTOMY SO DISEASES OF THE COLON & RECTUM LA English DT Article DE FULMINANT; ULCERATIVE COLITIS; ILEAL POUCH ID POUCH-ANAL ANASTOMOSIS; TOXIC MEGACOLON; ILEAL RESERVOIR; ILEOSTOMY; COLECTOMY; SURGERY AB Severe acute ulcerative colitis unresponsive to medical management is characterized by multiple associated risk factors including anemia, hypoproteinemia, and high steroid requirements when urgent surgery is required. Current surgical options include use of primary ileal pouch-anal anastomosis (IPAA) vs. historic trends favoring colectomy with ileostomy. PURPOSE: To evaluate the efficacy of primary IPAA in patients with severe colitis, we reviewed our own experience in 20 patients with this condition. METHODS: Patients undergoing primary restorative proctocolectomy included 13 males and 7 females (mean age, 30.5 +/- 2.4 years). Exclusion criteria for primary reconstruction included septic patients and patients with associated medical conditions such as pulmonary or cardiovascular disease. History of ulcerative colitis averaged 3.1 +/- 1.1 years (range, 1 month to 19 years). Preoperative mean total serum protein concentration was 5.0 +/- 0.2 g/dl, and mean albumin concentration was 2.1 +/- 0.2 g/dl, reflecting disease severity. The average daily steroid requirement at the time of urgent colectomy was 58.0 +/- 4.4 mg of prednisone (or intravenous equivalent). Primary IPAA included 18 ''W'' reservoirs, 1 ''S'' reservoir, and 1 ''J'' reservoir. RESULTS: Major surgical complications included mild pancreatitis (10 percent), anastomotic leak (5 percent), adrenal insufficiency (15 percent), an upper gastrointestinal bleed (5 percent), and small bowel obstruction (15 percent). There were no deaths, and no patients developed pelvic sepsis or required IPAA removal. At three and twelve months, 24-hr stool frequency averaged 7.3 +/- 0.4 and 4.9 +/- 0.3, respectively. Overall day and night continence was excellent and not different from patients who underwent elective IPAA procedures for ulcerative colitis. CONCLUSIONS: Improved options such as primary IPAA may be safely used in selected patients requiring urgent surgery for severe or fulminant ulcerative colitis. Medical management should be abbreviated when disease control cannot be promptly achieved. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. RP HARMS, BA (reprint author), UNIV WISCONSIN,DEPT SURG,H4-740,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 25 TC 16 Z9 16 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD OCT PY 1994 VL 37 IS 10 BP 971 EP 978 DI 10.1007/BF02049307 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA PM204 UT WOS:A1994PM20400002 PM 7924717 ER PT J AU LEE, CW GARDELLA, TJ ABOUSAMRA, AB NUSSBAUM, SR SEGRE, GV POTTS, JT KRONENBERG, HM JUPPNER, H AF LEE, CW GARDELLA, TJ ABOUSAMRA, AB NUSSBAUM, SR SEGRE, GV POTTS, JT KRONENBERG, HM JUPPNER, H TI ROLE OF THE EXTRACELLULAR REGIONS OF THE PARATHYROID-HORMONE (PTH) PTH-RELATED PEPTIDE RECEPTOR IN HORMONE-BINDING SO ENDOCRINOLOGY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; EXPRESSION CLONING; MOLECULAR-CLONING; CYSTEINE RESIDUE-110; CALCITONIN RECEPTOR; PLASMA-MEMBRANE; PROTEIN; RHODOPSIN; CELL; IDENTIFICATION AB The PTH/PTH-related peptide receptor is a member of a newly discovered family of G-protein-coupled receptors. Strikingly conserved features among these receptors include the positioning of eight extracellular cysteines and several other residues that are located predominantly within the membrane-embedded region. Deletion mutants or receptors with point mutations of the highly conserved cysteine residues were transiently expressed in COS-7 cells to evaluate PTH binding and PTH-stimulated cAMP production. Deletion of residues 61-105, which are encoded by exon E2 in the PTH/PTH-related peptide receptor gene, did not affect receptor function. An epitope derived from Haemophilus influenza hemagglutinin was, therefore, introduced into this portion of most receptors to allow the independent assessment of cell surface expression. PTH binding capacity was not reduced by the deletion of residues 258 and 278 in the first extracellular loop. Receptors with deletion of either residues 31-47 in the amino-terminal extension or residues 431-440 in the third extracellular loop failed to bind PTH, although expression of the receptor on the cell surface was only marginally reduced. Most other receptor mutants, including those in which each of the six cysteines in the amino-terminus was replaced by serines, failed to be processed and/or expressed appropriately, whereas the substitution of cysteine-281 or -351 had a less severe effect. The combined replacement of both cysteines concomitantly increased PTH binding and cell surface expression, suggesting the formation of a disulfide bond between these two residues. Our data indicate that residues near the amino-terminus and within the third extracellular loop are necessary for ligand binding, whereas more than 25% of the receptor's extracellular region appears not to be involved. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK-11794] NR 39 TC 107 Z9 107 U1 0 U2 3 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 1994 VL 135 IS 4 BP 1488 EP 1495 DI 10.1210/en.135.4.1488 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PK877 UT WOS:A1994PK87700027 PM 7523099 ER PT J AU PAI, SY CALVO, V WOOD, M BIERER, BE AF PAI, SY CALVO, V WOOD, M BIERER, BE TI CROSS-LINKING CD28 LEADS TO ACTIVATION OF 70-KDA S6 KINASE SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T CELL RECEPTOR-CD3 COMPLEX; SERINE/THREONINE KINASES; PROLIFERATION; SIGNAL TRANSDUCTION; CELL CYCLE PROGRESSION ID T-CELL ACTIVATION; SIGNAL TRANSDUCTION; PROTEIN-KINASES; CYCLOSPORINE-A; LYMPHOCYTES-T; RAPAMYCIN; INTERLEUKIN-2; PATHWAYS; ANTIGEN; PHOSPHORYLATION AB Proliferation of T lymphocytes in response to antigen/MHC complexes is dependent upon the presence of a co-stimulatory signal; in its absence,T cells are rendered unresponsive to specific antigen. CD28 is a T cell surface glycoprotein that acts as a co-stimulatory molecule when combined with signals initiated by the T cell receptor-CD3 complex. While the biochemical signaling events following CD28 stimulation are still poorly defined, monoclonal antibodies (mAb) directed against CD28 have been shown to transduce a variety of early signals that are different in the presence of cross-linking antibody or the presence of phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC). Stimulation of human T cells with cross-linked anti-CD28 mAb alone resulted in the activation of 70-kDa (p70) S6 kinase, a rapamycin-sensitive serine/threonine kinase that is believed to be important for cell cycle progression. Activation of p70 S6 kinase through CD28 was inhibited by rapamycin. Activation of p70 S6 kinase also increased in response to cross-linked CD3, but followed a more rapid time course than activation via CD28. Cyclosporin A and FK506 had no effect on p70 S6 kinase activity initiated via either pathway. The combination of cross-linked CD28 and cross-linked CD3 had no more than an additive effect on the induction of p70 S6 kinase activity. Thus, recruitment of p70 S6 kinase activity appears to represent a common signal transduction event shared by both the CD28 and CD3 pathways of T cell activation. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RI Calvo, Victor/L-5024-2014 OI Calvo, Victor/0000-0002-5913-7058 NR 36 TC 36 Z9 36 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 1994 VL 24 IS 10 BP 2364 EP 2368 DI 10.1002/eji.1830241016 PG 5 WC Immunology SC Immunology GA PL987 UT WOS:A1994PL98700015 PM 7523138 ER PT J AU KOVACSOVICSBANKOWSKI, M ROCK, KL AF KOVACSOVICSBANKOWSKI, M ROCK, KL TI PRESENTATION OF EXOGENOUS ANTIGENS BY MACROPHAGES - ANALYSIS OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I AND CLASS-II PRESENTATION AND REGULATION BY CYTOKINES SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE MACROPHAGE; MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I; ANTIGEN PROCESSING; CYTOKINES ID MARROW-DERIVED MACROPHAGES; RESTRICTED LYMPHOCYTES-T; STIMULATORY FACTOR-I; BONE-MARROW; MONOCLONAL-ANTIBODY; PRESENTING CELLS; MOUSE MACROPHAGE; SOLUBLE-PROTEIN; SURFACE-ANTIGEN; RECOGNITION AB There is an antigen presenting cell (APC) in the lymphoid organs capable of presenting exogenous antigen (Ag) with major histocompatibility complex (MHC) class I molecules. This study was initiated to isolate clones of these APC to definitively establish their phenotype and to further study their properties. Murine bone marrow macrophages (BM M Phi) were immortalized by overexpressing myc and raf oncogenes. Five BM M Phi cell lines were generated that are phagocytic and expressed at their surface M Phi differentiation Ag. All five cell lines processed and presented exogenous ovalbumin (OVA) with MHC class I molecules. They all presented OVA-linked to a phagocytic substrate 10(2)-10(4)-fold more efficiently than soluble Ag. Clonal isolates of two of the M Phi cell lines had an identical phenotype and functional properties as the uncloned lines. These results definitively establish that M Phi are APC with the capacity of presenting exogenous Ag with MHC class I molecules. Interferon (IFN)-gamma interleukin-4, granulocyte-macrophage colony stimulating factor and lipopolysaccharide either alone or in combination induced little or no augmentation and in some cases decreased presentation of exogenous OVA with MHC class I. In contrast, all of M Phi activating factors increased MHC class I expression. Moreover, IFN-gamma increased the presentation of cytosolic OVA, demonstrating differences between the presentation of cytosolic Ag versus exogenous Ag with MHC class I. Finally, some lines constitutively processed and presented exogenous OVA with MHC class II while others only presented after stimulation with IFN-gamma. These results demonstrate that the pathways involved in the presentation of exogenous Ag with MHC class I and class II are independently regulated and that a cloned cell is capable of presenting exogenous Ag through both pathways. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP KOVACSOVICSBANKOWSKI, M (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI31337, AI20248] NR 44 TC 80 Z9 81 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 1994 VL 24 IS 10 BP 2421 EP 2428 PG 8 WC Immunology SC Immunology GA PL987 UT WOS:A1994PL98700023 PM 7925570 ER PT J AU OKUDA, K MATULONIS, U SALGIA, R KANAKURA, Y DRUKER, B GRIFFIN, JD AF OKUDA, K MATULONIS, U SALGIA, R KANAKURA, Y DRUKER, B GRIFFIN, JD TI FACTOR INDEPENDENCE OF HUMAN MYELOID-LEUKEMIA CELL-LINES IS ASSOCIATED WITH INCREASED PHOSPHORYLATION OF THE PROTOONCOGENE RAF-1 SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE FACTOR-INDEPENDENT AND-DEPENDENT MYELOID CELLS; AML ID COLONY-STIMULATING FACTOR; ACUTE MYELOBLASTIC-LEUKEMIA; SIGNAL TRANSDUCTION; KINASE-ACTIVITY; C-RAF; TYROSINE PHOSPHORYLATION; RAPID PHOSPHORYLATION; BONE-MARROW; GM-CSF; GROWTH AB The proliferation of normal hematopoietic cells is strictly factor dependent, while leukemic cell lines and primary leukemic cells are frequently factor independent. Although autocrine growth stimulation of human leukemias is occasionally observed in vitro, it is possible that mutations of signal-transduction or cell-cycle control genes may also be important in the development of factor independence. We have previously shown that the proto-oncogene Raf-1, a 70-kd serine/threonine protein kinase, is rapidly phosphorylated and activated by hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and Steel factor and is likely to be an important intermediate in mitogenic signal transduction pathways in hematopoietic cells. In an effort to better understand the possible role of abnormal signal transduction in the development of factor independence, we compared the state of phosphorylation and associated kinase activity of Raf-1 between a series of factor-dependent human and murine-myeloid normal cells or cell lines and a series of factor-independent myeloid cell lines. In factor-dependent myeloid cells (normal neutrophils; monocytes; and the cell lines MO7, 32Dcl3, and FDC-P1), Raf-1 phosphorylation and associated kinase activity was strictly regulated by the supply of growth factor. In contrast, each of eight factor-independent leukemic cell lines examined, HL-60, KG-1, K562, U937, JOSK-S, JOSK-M, JOSK-K, and JOSK-I, expressed hyperphosphorylated Raf-1 with increased Raf-1-associated kinase activity in the absence of growth factor addition. To further explore the relationship of Raf-1 to factor-independent growth, factor-independent sublines were derived from two factor-dependent cell lines, MO7 and FDC-P1, by culture in CSF-deprived medium. Also, several factor-independent sublines were derived by transfection of a cDNA encoding p210(BCR/ABL) into three different cell lines: MO7, 32Dcl3, and FDC-P1. In each case, the new sublines expressed constitutively hyperphosphorylated and activated Raf-1. The correlation of hyperphosphorylation of Raf-1 with factor independence was also observed with primary acute myeloblastic leukemia cells. The rate of ''spontaneous'' proliferation of primary acute myeloblastic leukemia (AML) cells in vitro correlated with the extent of Raf-1 phosphorylation. These results suggest that the evolution of myeloid leukemic cells to factor independence is associated with phosphorylation and activation of Raf-1, implicating Raf-1 and,signal transduction pathways which activate Raf-1 in this process. RP GRIFFIN, JD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA34183, CA36167, CA47843] NR 38 TC 62 Z9 63 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 1994 VL 22 IS 11 BP 1111 EP 1117 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PL250 UT WOS:A1994PL25000011 PM 7925778 ER PT J AU BROUILLET, E HYMAN, BT JENKINS, BG HENSHAW, DR SCHULZ, JB SODHI, P ROSEN, BR BEAL, MF AF BROUILLET, E HYMAN, BT JENKINS, BG HENSHAW, DR SCHULZ, JB SODHI, P ROSEN, BR BEAL, MF TI SYSTEMIC OR LOCAL-ADMINISTRATION OF AZIDE PRODUCES STRIATAL LESIONS BY AN ENERGY IMPAIRMENT-INDUCED EXCITOTOXIC MECHANISM SO EXPERIMENTAL NEUROLOGY LA English DT Article ID CYANIDE-INDUCED PARKINSONISM; TOXIN 3-NITROPROPIONIC ACID; D-ASPARTATE RECEPTOR; HUNTINGTONS-DISEASE; METABOLISM; GLUTAMATE; BRAIN; IMMUNOREACTIVITY; INHIBITION; SUBSTANCE AB Sodium azide is an inhibitor of cytochrome oxidase which produces selective striatal lesions in both rodents and primates. In the present study we investigated the neurochemical and histologic effects of both intrastriatal and systemic administration of sodium azide, as well as the age dependence and mechanism of the lesions. Intrastriatal administration of sodium azide produced dose-dependent lesions. Neurochemical and histologic evaluation showed that markers of both spiny projection neurons (GABA, substance P) and aspiny interneurons (somatostatin, neuropeptide Y, NADPH-diaphorase) were equally affected. Subacute systemic administration of sodium azide resulted in lesions with a similar neurochemical profile; however, in contrast to intrastriatal injections there was sparing of dopaminergic striatal afferents. Prior decortication significantly attenuated lesions produced by intrastriatal administration of sodium azide, consistent with an excitotoxic process. Chronic administration of sodium azide for 1 month lead to striatal neuropathological changes. Lesions produced by intrastriatal administration of sodium azide in 1-, 4-, and 12-monthh old animals showed age dependence. Both freeze clamp measurements and chemical-shift magnetic resonance spectroscopy confirmed that sodium azide impairs oxidative phosphorylation in the striatum following either intrastriatal or systemic administration. These results show that the striatum is particularly vulnerable to oxidative stress produced by sodium azide, and that it produces striatal lesions by a secondary excitotoxic mechanism. (C) 1994 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,NEUROL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,MGH NMR CTR,BOSTON,MA 02114. RP BROUILLET, E (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,NEUROCHEM LAB,BOSTON,MA 02114, USA. RI Schulz, Jorg/D-9786-2012; Brouillet, Emmanuel/B-4784-2014 OI Schulz, Jorg/0000-0002-8903-0593; Brouillet, Emmanuel/0000-0001-6322-7403 FU NINDS NIH HHS [NS 10828, NS 31579]; PHS HHS [16367] NR 44 TC 29 Z9 29 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1994 VL 129 IS 2 BP 175 EP 182 DI 10.1006/exnr.1994.1159 PG 8 WC Neurosciences SC Neurosciences & Neurology GA PT226 UT WOS:A1994PT22600001 PM 7525331 ER PT J AU WESSELMANN, U KERNS, JM RYMER, WZ AF WESSELMANN, U KERNS, JM RYMER, WZ TI LASER EFFECTS ON MYELINATED AND NONMYELINATED FIBERS IN THE RAT PERONEAL NERVE - A QUANTITATIVE ULTRASTRUCTURAL ANALYSIS SO EXPERIMENTAL NEUROLOGY LA English DT Article ID NEURAL IMPULSE PROPAGATION; SCIATIC-NERVE; ND-YAG; HORSERADISH-PEROXIDASE; NEUROFILAMENT TRANSPORT; SENSORY AXONS; TIBIAL NERVE; OPTIC-NERVE; MICROTUBULES; IRRADIATION AB We have recently shown that Nd:YAG laser irradiation of rat peripheral nerve differentially impairs action potential transmission in small, slowly conducting sensory fibers compared to fast conducting afferents. In addition, the number of small sensory neurons of the A-delta- and C-fiber group labeled with HRP is significantly reduced after laser irradiation, while the number of labeled large sensory neurons and motoneurons was not affected. To further evaluate this laser-induced injury, we examined three distinct regions of the laser-irradiated rat peroneal nerve using ultrastructural morphometric methods. These regions were the site of laser irradiation and zones 10 mm proximal and 5 mm distal to the injury. The contralateral nerve was sham treated. Our results indicate that for the small nonmyelinated fibers, there was a significant increase in both mean fiber size and the number of microtubules per fiber, but a decrease in the number of neurofilaments. In contrast, the number of myelinated and nonmyelinated fibers is not significantly altered at 7 days following laser irradiation, and the mean diameter and frequency distribution of myelinated nerve fibers was unchanged. This study demonstrates that selective functional alterations in laser-irradiated nerves (nerve conduction velocity, HRP transport properties) are accompanied by ultrastructural changes of axonal organelles in nonmyelinated fibers. Nd:YAG laser light might ultimately prove to be a powerful tool to selectively alter functional properties in small, slowly conducting afferent fibers, without causing degeneration at the ultrastructural level at the site of irradiation. We hypothesize further that the laser induced functional alterations might be related to differential thermally mediated changes. (C) 1994 Academic Press, Inc. C1 NORTHWESTERN UNIV,SCH MED,DEPT PHYSIOL,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,DEPT PHYS MED & REHABIL,CHICAGO,IL 60611. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR PAIN,BOSTON,MA 02114. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT ANAT,CHICAGO,IL 60612. NR 44 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 1994 VL 129 IS 2 BP 257 EP 265 DI 10.1006/exnr.1994.1168 PG 9 WC Neurosciences SC Neurosciences & Neurology GA PT226 UT WOS:A1994PT22600010 PM 7525332 ER PT J AU PRINZ, C SACHS, G WALSH, JH COY, DH WU, SV AF PRINZ, C SACHS, G WALSH, JH COY, DH WU, SV TI THE SOMATOSTATIN RECEPTOR SUBTYPE ON RAT ENTEROCHROMAFFIN-LIKE CELLS SO GASTROENTEROLOGY LA English DT Article ID G-PROTEIN; MOLECULAR-CLONING; ENDOCRINE-CELLS; AFFINITY; STOMACH; BRAIN; ANTIBODIES; EXPRESSION; INHIBITION; HISTAMINE AB Background/Aims: Gastric enterochromaffinlike (ECL) cells play an important role in peripheral regulation of acid secretion. This study investigated the somatostatin receptor subtype on ECL cells. Methods: ECL cells were isolated from rat fundic mucosa to a purity of 90%-95% by combining enzymatic digestion, elutriation, density gradient centrifugation, and culture. Results: Polymerase chain reaction performed with templates from an ECL cell complementary DNA library and primers specific to each of the five known somatostatin receptor subtypes showed that the somatostatin receptor type 2 was significantly enriched in ECL complementary DNA. Single cell videoimaging of highly purified ECL cells in culture showed that only the somatostatin receptor type 2 selective agonist, DC 32-87, inhibited the gastrin-induced calcium signal at 10(-11) mol/L. The type 3 and type 4 selective agonists, DC 25-12 and DC 32-92, and also somatostatin 14 required 100-1000 times higher concentrations (10(-8) mol/L). The somatostatin receptor type 2 analogue also inhibited gastrin-stimulated histamine release with a 50% inhibitory concentration (IC50 value of 2 x 10(-12) mol/L, whereas somatostatin 14 and the type 3 and 4 analogues showed IC50 values of 1 to 5 x 10(-9) mol/L. Conclusions: The predominant somatostatin receptors on rat gastric ECL cells are of the somatostatin receptor 2 subtype; they inhibit histamine secretion by interfering with the gastrin-induced calcium signal. C1 UNIV CALIF LOS ANGELES,CTR ULCER RES & EDUC,CTR GASTROENTER BIOL,DEPT MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. TULANE UNIV,DEPT MED,NEW ORLEANS,LA 70118. FU NIDDK NIH HHS [DK17294, DK40615, DK41301] NR 27 TC 116 Z9 116 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 OCT PY 1994 VL 107 IS 4 BP 1067 EP 1074 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PJ586 UT WOS:A1994PJ58600019 PM 7523214 ER PT J AU MARRA, F CHOUDHURY, GG PINZANI, M ABBOUD, HE AF MARRA, F CHOUDHURY, GG PINZANI, M ABBOUD, HE TI REGULATION OF PLATELET-DERIVED GROWTH-FACTOR SECRETION AND GENE-EXPRESSION IN HUMAN LIVER FAT-STORING CELLS SO GASTROENTEROLOGY LA English DT Article ID SIMIAN SARCOMA-VIRUS; FACTOR-A-CHAIN; RAT HEPATIC LIPOCYTES; EXTRACELLULAR-MATRIX; ITO CELLS; CONDITIONED MEDIUM; MESSENGER-RNA; PDGF-B; V-SIS; FIBROSIS AB Background/Aims: Liver fat-storing cells (FSCs) actively proliferate and secrete extracellular matrix during liver injury. Platelet-derived growth factor (PDGF) is a potent mitogen for cultured FSCs. In the present study, we investigated the regulation of PDGF gene expression and production in cultured human liver FSCs. Methods: PDGF A-chain and B-chain expression was analyzed by Northern blotting and ribonuclease protection assay, respectively. Secretion of PDGF was evaluated by immunoprecipitation and immunoblotting of conditioned medium and metabolic labeling of FSC followed by immunoprecipitation. Results: Three PDGF A-chain transcripts were detectable. Stimulation of FSC with phorbol myristate acetate (10(-7) mol/L) or PDGF BB (20 ng/mL) increased steady-state levels of PDGF A-chain and B-chain messenger RNA. PDGF AA had a small stimulatory effect on A-chain but not B-chain messenger RNA levels. FSCs secrete PDGF in the conditioned medium. The secreted protein is bioactive, because concentrated conditioned medium induced an increase in thymidine incorporation that was inhibited by anti-PDGF antibodies. Conclusions: This study shows that cultured FSCs express PDGF A- and B-chain genes and release bioactive PDGF in the culture medium. These data raise the possibility of an autocrine or short-loop paracrine effect of PDGF in FSCs as a mechanism contributing to the maintenance of the proliferative state during liver injury. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET AFFAIRS HOSP,SAN ANTONIO,TX. UNIV FLORENCE,MED CLIN 2,FLORENCE,ITALY. RI Marra, Fabio/K-7263-2016 OI Marra, Fabio/0000-0001-8629-0878 FU NIDDK NIH HHS [DK-33665, DK-43988] NR 40 TC 45 Z9 45 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 OCT PY 1994 VL 107 IS 4 BP 1110 EP 1117 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PJ586 UT WOS:A1994PJ58600024 PM 7926460 ER PT J AU MURAMATSU, Y YAMADA, T MIURA, M SAKAI, T SUZUKI, Y SERIKAWA, T TANZI, RE MATSUMOTO, K AF MURAMATSU, Y YAMADA, T MIURA, M SAKAI, T SUZUKI, Y SERIKAWA, T TANZI, RE MATSUMOTO, K TI WILSONS-DISEASE GENE IS HOMOLOGOUS TO HTS CAUSING ABNORMAL COPPER TRANSPORT IN LONG-EVANS CINNAMON RATS SO GASTROENTEROLOGY LA English DT Note ID HEREDITARY HEPATITIS; LEC RATS; ACCUMULATION; ATPASE; LOCUS; MOUSE AB Background/Aims: The Long-Evans Cinnamon (LEC) mutant rat shows an excess copper accumulation in the liver and low serum ceruloplasmin activity. The disorder is controlled by a single autosomal recessive gene designated as hts. Wilson's disease is an autosomal recessive disorder of copper metabolism characterized by abnormal copper accumulation in the liver and tow serum ceruloplasmin activity. The gene responsible for Wilson's disease has recently been isolated. The present study was designed to examine whether the LEC rat is an ideal animal model for Wilson's disease from a genetic point of view. Methods: For chromosomal mapping of hts, genetic linkage analysis using rat microsatellite marker loci was performed. Furthermore, cosegregation between hts and a rat counterpart of the Wilson's disease gene was analyzed. Results: hts was finely mapped to rat chromosome 16. Complete cosegregation between hts and a rat counterpart of the Wilson's disease gene was detected. Conclusions: hts is likely to correspond to a rat homologue of the Wilson's disease gene. The present results allow us to propose that the LEC rat is an ideal animal model for Wilson's disease. C1 UNIV TOKUSHIMA,SCH MED,INST ANIM EXPT,TOKUSHIMA 770,JAPAN. UNIV TOKUSHIMA,SCH MED,DEPT HYG,TOKUSHIMA 770,JAPAN. KYOTO UNIV,FAC MED,INST LAB ANIM,KYOTO 606,JAPAN. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 24 TC 38 Z9 38 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 OCT PY 1994 VL 107 IS 4 BP 1189 EP 1192 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PJ586 UT WOS:A1994PJ58600035 PM 7926469 ER PT J AU SCHARRE, DW MAHLER, ME AF SCHARRE, DW MAHLER, ME TI PARKINSONS-DISEASE - MAKING THE DIAGNOSIS, SELECTING DRUG THERAPIES SO GERIATRICS LA English DT Article ID LEVODOPA AB Parkinson's disease is a progressive neurodegenerative condition of unknown cause and with no known cure. The diagnosis is based on clinical findings of rest tremor, muscle rigidity, bradykinesia, and gait instability. Over 40% of patients develop a dementia syndrome that is largely distinct from Alzheimer's disease. Depression is common, also occurring in more than 40% of patients with PD. Careful evaluation is necessary to help distinguish Parkinson's disease from secondary causes of parkinsonism. Carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B inhibitors are the main-stays of treatment. Anticholinergics and other agents may also be useful. Pharmacologic treatment must be carefully titrated to control symptoms and to avoid side effects. In advanced disease, dose-related dyskinesias, end-of-dose wearing-off effect, and unpredictable sudden motor fluctuations become very disabling and difficult to manage. C1 UNIV CALIF LOS ANGELES, SCH MED, REED NEUROL RES CTR, LOS ANGELES, CA USA. W LOS ANGELES VA MED CTR, NEUROBEHAV UNIT, LOS ANGELES, CA USA. NR 21 TC 6 Z9 6 U1 0 U2 2 PU ADVANSTAR COMMUNICATIONS INC PI DULUTH PA 131 W 1ST STREET, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD OCT PY 1994 VL 49 IS 10 BP 14 EP + PG 0 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA PL101 UT WOS:A1994PL10100002 PM 7926845 ER PT J AU GERETY, MB AF GERETY, MB TI HEALTH-CARE REFORM FROM THE VIEW OF A GERIATRICIAN SO GERONTOLOGIST LA English DT Article ID CONTROLLED TRIAL; MEDICINE; UNIT; WILL C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,SAN ANTONIO,TX 78285. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN MED,SAN ANTONIO,TX 78285. RP GERETY, MB (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN 182,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 28 TC 4 Z9 4 U1 2 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 1994 VL 34 IS 5 BP 590 EP 597 PG 8 WC Gerontology SC Geriatrics & Gerontology GA PX801 UT WOS:A1994PX80100006 PM 7959123 ER PT J AU HEILIGENHAUS, A FOSTER, CS AF HEILIGENHAUS, A FOSTER, CS TI HISTOLOGICAL AND IMMUNOPATHOLOGICAL ANALYSIS OF T-CELLS MEDIATING MURINE HSV-1 KERATITIS SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; STROMAL KERATITIS; CORNEAL INFECTION; ANTIGEN RECEPTOR; INBRED MICE; ANTIBODY; MOUSE; SPECIFICITY; RESISTANCE AB Background: Thymus-derived lymphocytes play a critical role in the development of herpes simplex keratitis (HSK). T-cell subsets defined by their expression of Various T-cell receptor (TCR) VP segments were studied following corneal HSV-1 infection (p.i.). Methods: Conjunctiva, corneal limbus and corneal stroma of two inbred BALB/c congenic mouse strains which differ only in the gene products closely linked to the Igh-1 locus on chromosome 12 were analyzed. Results: While C.B-17 mice (Igh-1(b)) were resistant to HSK, C.AL-20 mice (Igh-1(d)) clinically developed severe necrotizing keratitis by day 11 p.i. The corneal stroma of C.B-17 mice remained clear, while it was increasingly infiltrated by mononuclear cells and neutrophils in C.AL-20 mice by day 11 p.i. In C.B-17 mice, Thy1.2+ cells were found in the conjunctiva between days 2 to 4 p.i., and subsequently decreased. Only a few Thy1.2+ cells were found in the limbus, and no such cells were found in the stroma. In contrast, in C.AL-20 mice the numbers of Thy1.2+ cells (activated CD4+, V beta 8+ T cells) profoundly increased in the conjunctiva by day 4 p.i. These cells infiltrated the limbus between days 7 and 11 p.i. and eventually entered the stromal tissue by day 11 p.i. Conclusions: Our data suggest that the HSV-1-induced corneal tissue destruction is mediated by mononuclear cells and neutrophils and that these cells are probably attracted into the cornea by cytokines elaborated by activated CD4+, V beta 8+ T cells. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,HILLES IMMUNOL LAB,BOSTON,MA 02114. FU NEI NIH HHS [EY-06008] NR 40 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD OCT PY 1994 VL 232 IS 10 BP 628 EP 634 DI 10.1007/BF00193124 PG 7 WC Ophthalmology SC Ophthalmology GA PG078 UT WOS:A1994PG07800009 PM 8001832 ER PT J AU BRUGGE, WR AF BRUGGE, WR TI EXPANDING THE DIAGNOSTIC CAPABILITIES OF ENDOSCOPY - COMMON BILE-DUCT STONES SO HEPATOLOGY LA English DT Note RP BRUGGE, WR (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. NR 6 TC 1 Z9 1 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 1994 VL 20 IS 4 BP 1095 EP 1096 DI 10.1002/hep.1840200445 PN 1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PJ592 UT WOS:A1994PJ59200044 PM 7927214 ER PT J AU ALVAREZ, O MALDONADO, AL SPEEG, KV AF ALVAREZ, O MALDONADO, AL SPEEG, KV TI EFFECT OF BILE-DUCT OBSTRUCTION AND STENTING ON P-GLYCOPROTEIN CONTENT AND FUNCTION STUDIED IN-VIVO IN THE RAT SO HEPATOLOGY LA English DT Meeting Abstract C1 UT,HLTH SCI CTR,DEPT MED,DIV GASTROENTEROL,SAN ANTONIO,TX. AL MURPHY VET ADM HOSP,SAN ANTONIO,TX. 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 1994 VL 20 IS 4 BP A187 EP A187 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600362 ER PT J AU BALDRIDGE, AD GRAMECOOKE, F BANNER, B PEREZ, A HIGGINS, L LAVINE, JE AF BALDRIDGE, AD GRAMECOOKE, F BANNER, B PEREZ, A HIGGINS, L LAVINE, JE TI IDIOPATHIC STEATOSIS IN CHILDHOOD - ONSET, PRESENTATION AND ETIOLOGY SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,CTR CHILDHOOD LIVER DIS,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV MASSACHUSETTS,MED CTR,DEPT PATHOL,WORCESTER,MA 01605. 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 1994 VL 20 IS 4 BP A325 EP A325 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600909 ER PT J AU BHAVANI, K CHISARI, FV ITO, T WANDS, JR AF BHAVANI, K CHISARI, FV ITO, T WANDS, JR TI INCREASED TYROSYL PHOSPHORYLATION OF INSULIN-RECEPTOR SUBSTRATE-1 IN HCC TUMORS DERIVED FROM HBV SURFACE-ANTIGEN TRANSGENIC MICE SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC, MOLEC HEPATOL LAB, BOSTON, MA USA. SCRIPPS RES INST, LA JOLLA, CA USA. RI Chisari, Francis/A-3086-2008 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 1994 VL 20 IS 4 BP A273 EP A273 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600702 ER PT J AU CARTER, EA TOMPKINS, RG BABICH, JW FISCHMAN, AJ AF CARTER, EA TOMPKINS, RG BABICH, JW FISCHMAN, AJ TI EFFECT OF THERMAL-INJURY ON UPTAKE AND PHOSPHORYLATION OF F-18 FLUORODEOXYGLUCOSE (FDG) SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SHRINERS BURNS INST,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 1994 VL 20 IS 4 BP A336 EP A336 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600956 ER PT J AU DIENSTAG, JL PERRILLO, RP SCHIFF, ER BARTHOLOMEW, M VICARY, C RUBIN, M AF DIENSTAG, JL PERRILLO, RP SCHIFF, ER BARTHOLOMEW, M VICARY, C RUBIN, M TI DOUBLE-BLIND, RANDOMIZED, 3-MONTH, DOSE-RANGING TRIAL OF LAMIVUDINE FOR CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MIAMI,MIAMI,FL 33152. ALTON OCHSNER MED FDN & OCHSNER CLIN,NEW ORLEANS,LA 70121. GLAXO RES INST,RES TRIANGLE PK,NC. NR 1 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A199 EP A199 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600410 ER PT J AU HASEGAWA, K KATO, J TORII, N SHIZUMA, T YAMAUCHI, K HAYASHI, N LIANG, TJ AF HASEGAWA, K KATO, J TORII, N SHIZUMA, T YAMAUCHI, K HAYASHI, N LIANG, TJ TI HEPATIC EXPRESSION AND SECRETION OF HEPATITIS-B VIRAL PROTEIN FOLLOWED BY CIRCULATING ANTIBODY IN MICE SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. TOKYO WOMENS MED COLL,INST GASTROENTEROL,TOKYO 162,JAPAN. 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 1994 VL 20 IS 4 BP A303 EP A303 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600822 ER PT J AU HUANG, JK KWONG, J BEI, HC LIANG, TJ AF HUANG, JK KWONG, J BEI, HC LIANG, TJ TI IDENTIFICATION AND CHARACTERIZATION OF PROTEASOME AS THE CELLULAR TARGET OF HEPATITIS-B VIRAL X-PROTEIN SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,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 1994 VL 20 IS 4 BP A305 EP A305 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600829 ER PT J AU ITO, T TANAKA, S WANDS, JR AF ITO, T TANAKA, S WANDS, JR TI OVEREXPRESSION OF THE HUMAN INSULIN-RECEPTOR SUBSTRATE-1 (HIRS-1) GENE INDUCES CELLULAR-TRANSFORMATION THROUGH MITOGEN-ACTIVATED PROTEIN-KINASES (MAPKS) SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL,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 1994 VL 20 IS 4 BP A273 EP A273 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600703 ER PT J AU LINDSAY, KL SPENCER, C NICOLOFF, J MILSTEIN, S DAVIS, GL SCHIFF, E BODENHEIMER, H BALART, L DIENSTAG, J PERRILLO, R TAMBURRO, C EYERSON, G SANGHVI, B ALBRECHT, J AF LINDSAY, KL SPENCER, C NICOLOFF, J MILSTEIN, S DAVIS, GL SCHIFF, E BODENHEIMER, H BALART, L DIENSTAG, J PERRILLO, R TAMBURRO, C EYERSON, G SANGHVI, B ALBRECHT, J TI THYROID PEROXIDASE ANTIBODY - A POTENTIAL PREDICTOR OF IFN-ASSOCIATED THYROID-DISEASE SO HEPATOLOGY LA English DT Meeting Abstract C1 UNIV SO CALIF,LOS ANGELES,CA 90089. UNIV FLORIDA,GAINESVILLE,FL 32611. UNIV MIAMI,MIAMI,FL 33152. MT SINAI MED CTR,NEW YORK,NY 10029. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. WASHINGTON UNIV,ST LOUIS,MO 63130. UNIV LOUISVILLE,LOUISVILLE,KY 40292. UNIV COLORADO,DENVER,CO 80202. SCHERING PLOUGH CORP,KENILWORTH,NJ. 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 1994 VL 20 IS 4 BP A168 EP A168 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600285 ER PT J AU MORADPOUR, D COMPAGNON, B NICOLAU, C WANDS, JR AF MORADPOUR, D COMPAGNON, B NICOLAU, C WANDS, JR TI SPECIFIC TARGETING OF HUMAN HEPATOCELLULAR-CARCINOMA CELLS BY IMMUNOLIPOSOMES IN-VITRO SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BLOOD RES & DEV LAB,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,MOLEC HEPATOL 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 1994 VL 20 IS 4 BP A277 EP A277 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600719 ER PT J AU MORADPOUR, D WAKITA, T TOKUSHIGE, K WANDS, JR AF MORADPOUR, D WAKITA, T TOKUSHIGE, K WANDS, JR TI 3 NOVEL MONOCLONAL-ANTIBODIES SPECIFIC FOR THE HEPATITIS-C VIRUS CORE PROTEIN SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,MOLEC HEPATOL LAB,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 1994 VL 20 IS 4 BP A230 EP A230 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600531 ER PT J AU REID, AE JEFFERS, LJ REDDY, KR AIZA, I SCHIFF, ER DIENSTAG, JL LIANG, TJ AF REID, AE JEFFERS, LJ REDDY, KR AIZA, I SCHIFF, ER DIENSTAG, JL LIANG, TJ TI HEPATITIS-C VIRUS GENOTYPES AND HEPATOCELLULAR-CARCINOMA SO HEPATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MIAMI,SCH MED,CTR LIVER DIS,MIAMI,FL 33152. VET ADM MED CTR,MIAMI,FL 33125. NR 1 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1994 VL 20 IS 4 BP A250 EP A250 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600612 ER PT J AU SCAGLIONI, PP MELEGARI, M WANDS, JR AF SCAGLIONI, PP MELEGARI, M WANDS, JR TI CHARACTERIZATION OF HEPATITIS-B VIRUS CORE MUTANTS THAT INHIBIT VIRAL REPLICATION SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,MOLEC HEPATOL LAB,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 1994 VL 20 IS 4 BP A265 EP A265 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600672 ER PT J AU TOKUSHIGE, K PACHUK, C WAKITA, T MORADPOUR, D WANG, B BOYER, J CONEY, L WEINER, DB WANDS, JR AF TOKUSHIGE, K PACHUK, C WAKITA, T MORADPOUR, D WANG, B BOYER, J CONEY, L WEINER, DB WANDS, JR TI DEVELOPMENT AND IMMUNE-RESPONSE TO HCV-CORE 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 02114. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. RI Weiner, David/H-8579-2014 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 1994 VL 20 IS 4 BP A230 EP A230 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600530 ER PT J AU TONG, SP LI, JS WANDS, JR AF TONG, SP LI, JS WANDS, JR TI CHARACTERIZATION OF A HEPATOCYTE MEMBRANE GLYCOPROTEIN THAT SPECIFICALLY BINDS TO THE PRE-S REGION OF THE DUCK HEPATITIS-B VIRUS SO HEPATOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL 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 1994 VL 20 IS 4 BP A303 EP A303 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PM556 UT WOS:A1994PM55600824 ER PT J AU GARDNER, E MULLIGAN, LM ENG, C HEALEY, CS KWOK, JBJ PONDER, MA PONDER, BAJ AF GARDNER, E MULLIGAN, LM ENG, C HEALEY, CS KWOK, JBJ PONDER, MA PONDER, BAJ TI HAPLOTYPE ANALYSIS OF MEN-2 MUTATIONS SO HUMAN MOLECULAR GENETICS LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-2A; HUMAN RET PROTOONCOGENE; FAMILIES; LINKAGE; SYSTEMS; 10Q11.2 AB Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome which affects thyroid C cells, and with variable frequency, the adrenal medulla, parathyroid and enteric autonomic ganglia. The syndrome is due to germline mutation in the receptor tyrosine kinase gene, RET. We have recently shown an unexpected correlation between one particular RET mutation, cys634-->arg, and the probability of parathyroid involvement in families with MEN 2A. Here we use haplotype analysis in the families to show that this correlation is not explained by a single founder chromosome which carries both the cys634-->arg mutation and a separate allele conferring susceptibility to parathyroid abnormality, but is probably due to the cys634-->arg mutation itself. The results also indicate that new mutations to MEN 2 are not infrequent. C1 UNIV CAMBRIDGE,DEPT PATHOL,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 1QP,ENGLAND. HARVARD UNIV,SCH MED,DEPT MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. OI Eng, Charis/0000-0002-3693-5145 NR 17 TC 22 Z9 23 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 OCT PY 1994 VL 3 IS 10 BP 1771 EP 1774 DI 10.1093/hmg/3.10.1771 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PN138 UT WOS:A1994PN13800008 PM 7849700 ER PT J AU UEKI, K RUBIO, MP RAMESH, V CORREA, KM RUTTER, JL VONDEIMLING, A BUCKLER, AJ GUSELLA, JF LOUIS, DN AF UEKI, K RUBIO, MP RAMESH, V CORREA, KM RUTTER, JL VONDEIMLING, A BUCKLER, AJ GUSELLA, JF LOUIS, DN TI MTS1/CDKN2 GENE-MUTATIONS ARE RARE IN PRIMARY HUMAN ASTROCYTOMAS WITH ALLELIC LOSS OF CHROMOSOME 9P SO HUMAN MOLECULAR GENETICS LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISM; GLIOMA CELL-LINES; LINKAGE MAP; SHORT ARM; DELETIONS; PROTEIN; TUMORS; LOCUS AB Human astrocytomas frequently have allelic losses of chromosome 9p, suggesting the presence of a 9p astrocytoma tumor suppressor gene. The MTS1 (or CDKN2) gene on chromosome 9p encodes a cell-cycle regulator and is deleted in approximately 80% of astrocytoma cell lines. To determine whether MTS1 is the tumor suppressor gene involved in human astrocytoma formation in vivo, we have analyzed chromosome 9p allelic loss and the MTS1 gene in 30 primary astrocytomas. Deletion mapping demonstrated 15 cases with allelic loss of chromosome 9p, with all losses either flanking or involving the MTS1 gene. Direct analysis of the MTS1 gene, however, revealed only a single missense mutation in a high-grade tumor that had lost the second allele. The low frequency of MTS1 mutations in primary astrocytomas with allelic 9p loss suggests that MTS1 may be more important for in vitro than in vivo astrocytoma growth, and that another 9p tumor suppressor gene may be involved in astrocytoma formation in vivo. Analysis of the MTS1 gene also demonstrated two intragenic polymorphisms, one in exon 2 and one in the 3' untranslated region, that can be used to assay allelic loss directly at MTS1. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,MOLEC NEUROONCOL LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. UNIV HOSP BONN,INST NEUROPATHOL,BONN,GERMANY. RI Rubio, Mari-Paz/K-4364-2014; von Deimling, Andreas/F-7774-2013; OI Rubio, Mari-Paz/0000-0003-3963-5903; von Deimling, Andreas/0000-0002-5863-540X; Rutter, Joni/0000-0002-6502-2361 FU NCI NIH HHS [CA 57683] NR 26 TC 122 Z9 122 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 1994 VL 3 IS 10 BP 1841 EP 1845 DI 10.1093/hmg/3.10.1841 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PN138 UT WOS:A1994PN13800021 PM 7849711 ER PT J AU VANKAER, L ASHTONRICKARDT, PG EICHELBERGER, M GACZYNSKA, M NAGASHIMA, K ROCK, KL GOLDBERG, AL DOHERTY, PC TONEGAWA, S AF VANKAER, L ASHTONRICKARDT, PG EICHELBERGER, M GACZYNSKA, M NAGASHIMA, K ROCK, KL GOLDBERG, AL DOHERTY, PC TONEGAWA, S TI ALTERED PEPTIDASE AND VIRAL-SPECIFIC T-CELL RESPONSE IN LMP2 MUTANT MICE SO IMMUNITY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; MULTICATALYTIC PROTEINASE COMPLEXES; PROTEASOME-RELATED GENE; MHC-LINKED LMP; ANTIGEN PRESENTATION; POSITIVE SELECTION; LYMPHOCYTES-T; LYMPH-NODE; SUBUNITS AB MHC class I molecules present peptides generated by processing of endogenously synthesized proteins to CD8(+) T lymphocytes. Recently, large proteolytic complexes, termed proteasomes, were implicated in antigen processing.Two proteasomal subunits, LMP2 and LMP7, are encoded within the MHC class II region, but their precise role in antigen processing is unknown. We have generated mice that harbor a disruption in their LMP2 gene. Proteasomes purified from spleen and liver of these mutant mice exhibit altered peptidase activities, and antigen-presenting cells showed reduced capacity to stimulate a T cell hybridoma specific for H-2D(b) plus a nucleoprotein epitope of an influenza A virus. The mutant mice have reduced (60%-70% of wild type) levels of CD8(+) T lymphocytes and generate 5- to B-fold fewer influenza nucleoprotein-specific cytotoxic T lymphocyte precursors. These findings indicate that LMPS influences antigen processing. C1 MIT, HOWARD HUGHES MED INST, CTR CANC RES, CAMBRIDGE, MA 02139 USA. MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA. ST JUDE CHILDRENS RES HOSP, DEPT IMMUNOL, MEMPHIS, TN 38105 USA. HARVARD UNIV, SCH MED, DEPT CELLULAR & MOLEC PHYSIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. RI Van Kaer, Luc/H-1033-2015; Doherty, Peter Charles/C-4185-2013 OI Van Kaer, Luc/0000-0001-5275-2309; Doherty, Peter Charles/0000-0002-5028-3489 NR 52 TC 228 Z9 231 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 1994 VL 1 IS 7 BP 533 EP 541 DI 10.1016/1074-7613(94)90043-4 PG 9 WC Immunology SC Immunology GA PN127 UT WOS:A1994PN12700002 PM 7600282 ER PT J AU SYKES, M LEE, LA SACHS, DH AF SYKES, M LEE, LA SACHS, DH TI XENOGRAFT TOLERANCE SO IMMUNOLOGICAL REVIEWS LA English DT Review ID BONE-MARROW CHIMERAS; MAJOR HISTOCOMPATIBILITY COMPLEX; NONLETHAL PREPARATIVE REGIMEN; MIXED ALLOGENEIC CHIMERAS; ANTIGEN-PRESENTING CELLS; SCID-HU MOUSE; NATURAL ANTIBODIES; T-CELLS; MONOCLONAL-ANTIBODIES; SELF-RECOGNITION C1 MASSACHUSETTS GEN HOSP EAST,TRANSPLANTAT BIOL RES CTR,SURG SERV,BOSTON,MA 02129. FU NHLBI NIH HHS [HL49915] NR 100 TC 58 Z9 59 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 1994 VL 141 BP 245 EP 276 DI 10.1111/j.1600-065X.1994.tb00880.x PG 32 WC Immunology SC Immunology GA PR097 UT WOS:A1994PR09700011 PM 7868155 ER PT J AU PITMAN, MB YOUNG, RH CLEMENT, PB DICKERSIN, GR SCULLY, RE AF PITMAN, MB YOUNG, RH CLEMENT, PB DICKERSIN, GR SCULLY, RE TI ENDOMETRIOID CARCINOMA OF THE OVARY AND ENDOMETRIUM, OXYPHILIC CELL-TYPE - A REPORT OF 9 CASES SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE OVARY; ENDOMETRIUM; ENDOMETRIOID CARCINOMA; OXYPHIL CELL ID CLINICOPATHOLOGICAL ANALYSIS; TUMORS; ADENOCARCINOMA; LIGHT AB Six endometrioid carcinomas of the ovary and three of the endometrium composed predominantly or entirely of large eosinophilic (oxyphilic) cells are reported. The ovarian tumors occurred in women 31-75 years of age, with a mean of 58 years, and the endometrial tumors occurred in women 37-50 years, with a mean of 44 years. All the ovarian tumors and one endometrial tumor contained focal areas typical of endometrioid carcinoma, with round to oval tubular glands lined by simple or stratified columnar cells and focal squamous differentiation. Two endometrial tumors were composed almost exclusively of oxyphilic cells lining glands. One endometrial tumor contained prominent luminal and intracytoplasmic mucin. Five of the ovarian tumors were grade 2/3 and one was grade 3/3, whereas two of the endometrial tumors were grade 1/3 and one was grade 2/3. The prominence of the oxyphilic cells posed diagnostic difficulty in most of the cases. Electron microscopic examination performed on all tumors showed abundant mitochrondria in only one, an ovarian tumor. Other organelles, especially microfilaments and tonofibrils, are cited as other possible reasons for the eosinophilia. Four of the nine cases were recent; follow-up of the remaining five showed a biological behavior similar to the typical endometrioid carcinoma of the ovary and endometrium. We suggest that the diagnosis of ''endometrioid carcinoma, oxyphilic cell type'' is appropriate for this variant of carcinoma largely composed of eosinophilic cells that may or may not be ''oncocytic'' in nature. The importance of recognizing this entity lies in distinguishing it from diverse other primary and metastatic oxyphilic cell tumors of the ovary and eosinophilic cell metaplasia and rare other types of primary carcinoma with eosinophilic cells of the endometrium, which may be especially challenging in a curettage or biopsy specimen. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV BRITISH COLUMBIA,VANCOUVER GEN HOSP,DEPT PATHOL,VANCOUVER V5Z 1M9,BC,CANADA. RP PITMAN, MB (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,32 FRUIT ST,BOSTON,MA 02114, USA. NR 15 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 1994 VL 13 IS 4 BP 290 EP 301 DI 10.1097/00004347-199410000-00002 PG 12 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA PJ352 UT WOS:A1994PJ35200002 PM 7814190 ER PT J AU YOUNG, RH OLIVA, E SCULLY, RE AF YOUNG, RH OLIVA, E SCULLY, RE TI LUTEINIZED ADULT GRANULOSA-CELL TUMORS OF THE OVARY - A REPORT OF 4 CASES SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE OVARY; GRANULOSA CELL TUMOR; LUTEINIZATION ID CLINICOPATHOLOGICAL ANALYSIS; STROMAL TUMORS; LEYDIG-CELL; CARCINOMA; THECOMAS AB Four luteinized adult granulosa cell tumors of the ovary in women 22-76 (average 53) years of age are described. Two patients presented with postmenopausal bleeding, one with dysfunctional uterine bleeding and one with amenorrhea. The tumors were ah stage Ia, ranged from 2 to 11 (average 5.1) cm in greatest dimension, and were typically solid, lobulated, and yellow. On microscopic examination the most striking feature was the abundant eosinophilic cytoplasm of most of the tumor cells, which resembled the granulosa cells of the corpus luteum. The tumor cells typically grew diffusely, but large nodules intersected by scanty fibrous septa were present in all the cases. Additional patterns present focally included cords or ribbons, nests, and thick trabeculae. The tumors had inconspicuous amounts of fibrothecomatous stroma; foci of stromal edema or myxoid change were present in three cases. The tumor cell nuclei were round, of moderate size, and pale, and many of them had nuclear grooves. There was no significant nuclear pleomorphism and the mitotic rate did not exceed 1 per 10 high power fields. Reticulum stains, available in three cases, confirmed the granulosa cell nature of the neoplasms by disclosing scanty intercellular fibrils in most areas. Immunostains, performed in two cases, showed positivity for vimentin in both of them and for cytokeratin, smooth-muscle actin, and S-100 in one. One tumor from a 75-year-old woman was associated with an ectopic decidual reaction in a periovarian adhesion. This patient had focal, severe atypical complex hyperplasia of the endometrium and focal secretory change in the endometrium uninvolved by the hyperplasia. A second postmenopausal patient had an infiltrating well differentiated endometrial adenocarcinoma. A 41-year-old woman had cystic endometrial hyperplasia. The fourth patient's endometrium was not examined. The prominent luteinization in these tumors caused diagnostic difficulty because it is in marked contrast to the scanty cytoplasm of the usual adult granulosa cell tumor. The architectural features of the neoplasms and the characteristic nuclear findings, which were typical for the adult granulosa cell tumor, facilitated their distinction from the juvenile granulosa cell tumor and several other neoplasms that occasionally entered into the differential diagnosis. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP YOUNG, RH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 38 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 1994 VL 13 IS 4 BP 302 EP 310 DI 10.1097/00004347-199410000-00003 PG 9 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA PJ352 UT WOS:A1994PJ35200003 PM 7814191 ER PT J AU AUGUST, M NGUYEN, M AF AUGUST, M NGUYEN, M TI EVALUATION OF METASTATIC NECK DISEASE BY COMPUTED-TOMOGRAPHY SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article DE ORAL CANCER; SQUAMOUS CELL CARCINOMA; LYMPH NODES; METASTATIC SPREAD; COMPUTED TOMOGRAPHY SCAN AB This study evaluated the accuracy of computed tomography (CT) scanning in the diagnosis of metastatic neck disease in primary squamous cell carcinoma of the oral cavity and oropharynx, and compared this modality with physical examination alone. The accuracy of the CT scan was found to be 62%, as compared with a 66% accuracy rate of physical examination. In cases of clinically enlarged lymph nodes, physical examination was found to be 71% accurate; the CT scan, 68% accurate. Both the sensitivity and the positive predictive value of the CT scan were lower than those of the physical examination in this patient population. C1 HARVARD UNIV,SCH DENT MED,CAMBRIDGE,MA 02138. RP AUGUST, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,FRUIT ST,WARREN 1201,BOSTON,MA 02114, USA. NR 8 TC 7 Z9 8 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0901-5027 J9 INT J ORAL MAX SURG JI Int. J. Oral Maxillofac. Surg. PD OCT PY 1994 VL 23 IS 5 BP 290 EP 293 DI 10.1016/S0901-5027(05)80111-0 PG 4 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA PY346 UT WOS:A1994PY34600009 PM 7890971 ER PT J AU WARSHAW, AL AF WARSHAW, AL TI PREVALENCE AND PATTERNS OF SPREAD IN EARLY PANCREATIC ADENOCARCINOMA SO INTERNATIONAL JOURNAL OF PANCREATOLOGY LA English DT Article; Proceedings Paper CT The NCI Workshop on Investigational Strategies for Detection and Intervention in Early-Stage Pancreatic Cancer CY APR 24-27, 1994 CL ANNAPOLIS, MD SP NCI, ORGAN SYST PROGRAM, DIV CANC BIOL DIAGNOSIS & CTR ID CANCER; CARCINOMA; THERAPY RP WARSHAW, AL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA, USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0169-4197 J9 INT J PANCREATOL JI Int. J. Pancreatol. PD OCT-DEC PY 1994 VL 16 IS 2-3 BP 225 EP 227 PG 3 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PN722 UT WOS:A1994PN72200027 ER PT J AU WARSHAW, AL AF WARSHAW, AL TI REDEFINING AND RECLASSIFYING EARLY PANCREATIC-CANCER SO INTERNATIONAL JOURNAL OF PANCREATOLOGY LA English DT Article; Proceedings Paper CT The NCI Workshop on Investigational Strategies for Detection and Intervention in Early-Stage Pancreatic Cancer CY APR 24-27, 1994 CL ANNAPOLIS, MD SP NCI, ORGAN SYST PROGRAM, DIV CANC BIOL DIAGNOSIS & CTR RP WARSHAW, AL (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0169-4197 J9 INT J PANCREATOL JI Int. J. Pancreatol. PD OCT-DEC PY 1994 VL 16 IS 2-3 BP 251 EP 252 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA PN722 UT WOS:A1994PN72200038 ER PT J AU GARPESTAD, E PARKER, JA KATAYAMA, H LILLY, J YASUDA, T RINGLER, J STRAUSS, HW WEISS, JW AF GARPESTAD, E PARKER, JA KATAYAMA, H LILLY, J YASUDA, T RINGLER, J STRAUSS, HW WEISS, JW TI DECREASE IN VENTRICULAR STROKE VOLUME AT APNEA TERMINATION IS INDEPENDENT OF OXYGEN DESATURATION SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE OBSTRUCTIVE SLEEP APNEA; HEMODYNAMICS; CARDIAC FUNCTION ID OBSTRUCTIVE SLEEP-APNEA; PRESSURE; HEMODYNAMICS; MANEUVER AB Patients with obstructive sleep apnea experience nocturnal hemodynamic oscillations in association with repetitive respiratory events. Apnea termination (recovery) is accompanied by the nadir of arterial O-2 saturation (Sa(o2)), changes in intrathoracic pressure, and arousal from sleep. To investigate separately the contributions of hypoxemia and of arousal from sleep to changes in cardiac function, we continuously measured left ventricular stroke volume (LVSV) and mean arterial pressure (MAP) in eight subjects with severe obstructive sleep apnea (apnea-hypopnea index > 30 events/h associated with Sa(o2) less than or equal to 82%) during two experimental conditions: 1) subjects slept without intervention for 1-2 h and then supplemental O-2 was administered to maintain Sa(o2) greater than or equal to 90% (mean Sa(o2) nadir 92.7%) throughout the apnea-recovery cycle and 2) upper airway obstructions were abolished using nasal continuous positive airway pressure and subjects were aroused from sleep by an auditory signal. Recovery was associated with an increase in MAP and a decrease in LVSV both with and without supplemental O-2. Arousal from sleep on nasal continuous positive airway pressure reproduced the postapneic elevation of MAP but not a decrease in cardiac function of the magnitude that occurred at apnea termination. We conclude that elevation of blood pressure and reduction of LVSV that occurred at apnea termination may be due to different physiological mechanisms. C1 BETH ISRAEL HOSP,SLEEP DISORDER CTR,CHARLES A DANA RES INST,DIV PULM,BOSTON,MA 02215. BETH ISRAEL HOSP,SLEEP DISORDER CTR,HARVARD THORNDIKE LAB,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT RADIOL,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-07633, HL-46951] NR 28 TC 39 Z9 39 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 1994 VL 77 IS 4 BP 1602 EP 1608 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PL694 UT WOS:A1994PL69400006 PM 7836175 ER PT J AU DUPONTVERSTEEGDEN, EE MCCARTER, RJ KATZ, MS AF DUPONTVERSTEEGDEN, EE MCCARTER, RJ KATZ, MS TI VOLUNTARY EXERCISE DECREASES PROGRESSION OF MUSCULAR-DYSTROPHY IN DIAPHRAGM OF MDX MICE SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE CONTRACTILE PROPERTIES; MUSCLES; RESPIRATORY MUSCLE; ENDURANCE TRAINING; DUCHENNE MUSCULAR DYSTROPHY ID CONTRACTILE PROPERTIES; SKELETAL-MUSCLE; DUCHENNE; MOUSE; ENDURANCE; EXPRESSION; WEAKNESS AB Effects of voluntary wheel running on contractile properties of diaphragm (DIA) and soleus (SOL) of dystrophic (mdx) and control (C57BL/10SNJ) mice were evaluated. In particular, we tested the hypothesis that daily voluntary running is not deleterious to muscle function in mdx mice. Both groups of mice ran extensively (control mice similar to 7 km/day, mdx mice similar to 5 km/day). Exercise increased maximal specific tetanus tension of mdx DIA from 1.02 +/- 0.04 to 1.33 +/- 0.06 kg/cm(2) but did not restore it to the control level (2.55 +/- 0.17 kg/cm(2)). Maximal tetanus tension of sedentary mdx SOL (2.41 +/- 0.17 kg/cm(2)) was reduced compared with control (3.10 +/- 0.15 kg/cm(2)) and was not altered by running activity. Optimal length was significantly lower in DIA of mdx mice, and exercise did not change this. Fatigability and contractile properties of muscles measured in vitro were not altered by running activity with the exception of increased contraction time in mdx DIA. In conclusion, extensive wheel running is not deleterious to muscle function in mdx mice contrary to predictions of the ''work overload'' theory of muscular dystrophy. Rather, this exercise is beneficial for active tension generation of melt DIA, the muscle most closely resembling muscles of patients with Duchenne muscular dystrophy. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,GERIATR RES EDUC & CLIN CTR,SAN ANTONIO,TX 78284. NR 32 TC 75 Z9 75 U1 0 U2 1 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 1994 VL 77 IS 4 BP 1736 EP 1741 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA PL694 UT WOS:A1994PL69400024 PM 7836193 ER PT J AU PUGLIESE, A AWDEH, ZL ALPER, CA JACKSON, RA EISENBARTH, GS AF PUGLIESE, A AWDEH, ZL ALPER, CA JACKSON, RA EISENBARTH, GS TI THE PATERNALLY INHERITED INSULIN GENE B-ALLELE (1,428-FOKI SITE) CONFERS PROTECTION FROM INSULIN-DEPENDENT DIABETES IN FAMILIES SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT 13th Immunology of Diabetes Workshop CY MAY 25-28, 1994 CL MONTVILARGENNE, FRANCE ID SUSCEPTIBILITY; MELLITUS; RISK; AUTOIMMUNITY; POLYMORPHISM; ASSAY; IGF2 AB Several polymorphisms of the insulin gene and its flanking regions (INS region) are in linkage disequilibrium and confer susceptibility to insulin-dependent diabetes (IDDM). We have analysed INS AA and AB-BB genotypes at the 1,428 FokI site (3' of the insulin gene) in 217 patients with IDDM, 402 non-diabetic first degree relatives negative for insulin (IAA) and isfet cell autoantibodies (ICA), and 116 autoantibody positive (for ICA or IAA, or both) relatives of whom 39 became diabetic on follow-up. Most IDDM patients (83.4%, 181/217) had the AA genotype vs. 50% (25/50) of the controls (P<10(-6)). Only 16.6% (36/217) of IDDM patients carried the AB genotype and none was BB homozygous, suggesting a protective effect of the B allele. By segregation analysis of the B allele in the IDDM offspring of informative families (only one AB parent) from the United States, the maternal B allele was inherited by 19/35 (54.2%) of the IDDM offspring. In contrast, only 4/26 (15.3%) of the IDDM offspring inherited the paternal B allele (P=0.001), suggesting maternal imprinting of the INS region. Therefore, the INS B allele may be protective only when paternally inherited. Among the 39 of 116 autoantibody positive relatives who developed IDDM on follow-up, only five of them had the B allele. The frequency of the B allele in this group was much lower (12.8%, 5/39) than that observed in non-diabetic autoantibody positive relatives (32.5%, 25/77, P=0.02). By lifetable analysis, autoantibody positive relatives with the B allele showed slower and lesser progression to IDDM than those without it (Log-rank test, P=0.04). In conclusion, we find a protective effect of the paternally inherited B allele in diabetic families from the United States and in their autoantibody positive first degree relatives. C1 UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABET,DENVER,CO 80262. HARVARD UNIV,JOSLIN DIABET CTR,CTR BLOOD RES,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [5 RO1 DK43279-04, 5 R37 DK32083-13] NR 17 TC 46 Z9 46 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD OCT PY 1994 VL 7 IS 5 BP 687 EP 694 DI 10.1006/jaut.1994.1053 PG 8 WC Immunology SC Immunology GA PL696 UT WOS:A1994PL69600014 PM 7840860 ER PT J AU FLEET, JC HOCK, JM AF FLEET, JC HOCK, JM TI IDENTIFICATION OF OSTEOCALCIN MESSENGER-RNA IN NONOSTEOID TISSUE OF RATS AND HUMANS BY REVERSE TRANSCRIPTION-POLYMERASE CHAIN-REACTION SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID GAMMA-CARBOXYGLUTAMIC ACID; CALCIUM-BINDING PROTEINS; K-DEPENDENT PROTEIN; MESSENGER-RNA; BONE; GENE; EXPRESSION; SEQUENCES; 1,25-DIHYDROXYVITAMIN-D; CALCIFICATION AB Diseased or necrotic tissue can become calcified in a way that resembles bone. We examined soft tissues for the presence and regulation of the mRNA for the bone-associated protein, osteocalcin (OC). RNA was isolated from liver, kidney, lung, brain, muscle, and bone of young (2 months) male SD rats and analyzed for beta-actin, IGF-I, metallothionein IIa, alpha(1) collagen, calbindin-D-9k (CaBP), and OC mRNA by reverse transcription-polymerase chain reaction (RT-PCR). All PCR products but CaBP were found in bone; CaBP was present only in duodenum, kidney, and lung. OC product was detected in all tissues; the identity of the PCR product was confirmed by sequencing. Bone OC mRNA levels were calculated to be 1000-fold higher than duodenal levels. Rats fed a 0.8% strontium diet for 7 days to drive down serum 1,25-dihydroxyvitamin D-3 levels [1,25(OH)(2)D-3] and then injected with 300 ng 1,25(OH)(2)D-3/100 body weight had increased duodenal CaBP (2.5-fold) and femur OC mRNA (2.2-fold) 24 h after treatment. Duodenal OC mRNA was unchanged. OC mRNA was found in nondiseased human aortae, and the amount of message was elevated in calcified aorta and calcified aortic plaques. These results demonstrate that (1) tissues other than bone have low basal expression of OC mRNA, (2) OC mRNA is not regulated by vitamin D in nonosteoid tissue, and (3) expression of OC mRNA in atherosclerotic aorta reflects a role for bone-forming cells in ectopic bone formation observed in certain disease conditions. C1 TUFTS UNIV,SCH DENT MED,BOSTON,MA 02111. US DEPT VET AFFAIRS,OUTPATIENT CLIN,BOSTON,MA. RP FLEET, JC (reprint author), TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,824 HNRCA,711 WASHINGTON ST,BOSTON,MA 02111, USA. FU NHLBI NIH HHS [P01-HL48743] NR 33 TC 80 Z9 83 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 1994 VL 9 IS 10 BP 1565 EP 1573 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PJ111 UT WOS:A1994PJ11100008 PM 7817802 ER PT J AU SMITH, TH KACHINSKY, AM MILLER, JB AF SMITH, TH KACHINSKY, AM MILLER, JB TI SOMITE SUBDOMAINS, MUSCLE-CELL ORIGINS, AND THE 4 MUSCLE REGULATORY FACTOR PROTEINS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HEAVY-CHAIN ISOFORMS; SKELETAL-MUSCLE; MYOGENIN GENE; EXPRESSION; MOUSE; DIFFERENTIATION; LINEAGES; ACTIVATION; EMBRYO; MYOD1 AB We show by immunohistology that distinct expression patterns of the four muscle regulatory factor (MRF) proteins identify subdomains of mouse somites. Myf-5 and MyoD are, at specific stages, each expressed in both myotome and dermatome cells. Myf-5 expression is initially restricted to dorsal cells in all somites, as is MyoD expression in neck somites. In trunk somites, however, MyoD is initially expressed in ventral cells. Myogenin and MRF4 are restricted to myotome cells, though the MRF4-expressing cells are initially less widely distributed than the myogenin-expressing cells, which are at all stages found throughout the myotome. AU semitic myocytes express one or more MRFs. The transiently distinct expression patterns of the four MRF proteins identify dorsal and ventral subdomains of somites, and suggest that skeletal muscle cells in somites originate at multiple sites and via multiple molecular pathways. C1 MASSACHUSETTS GEN HOSP,NEUROMUSCULAR LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. NR 47 TC 99 Z9 102 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT PY 1994 VL 127 IS 1 BP 95 EP 105 DI 10.1083/jcb.127.1.95 PG 11 WC Cell Biology SC Cell Biology GA PJ425 UT WOS:A1994PJ42500010 PM 7929574 ER PT J AU SCHROY, PC RUSTGI, AK IKONOMU, E LIU, XP POLITO, J ANDRY, C OKEANE, JC AF SCHROY, PC RUSTGI, AK IKONOMU, E LIU, XP POLITO, J ANDRY, C OKEANE, JC TI GROWTH AND INTESTINAL DIFFERENTIATION ARE INDEPENDENTLY REGULATED IN HT29 COLON-CANCER CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HUMAN COLORECTAL-CANCER; C-MYC EXPRESSION; PROTEIN-KINASE-C; SODIUM-BUTYRATE; ENTEROCYTIC DIFFERENTIATION; HEXAMETHYLENE BISACETAMIDE; CARCINOMA-CELLS; MONOCLONAL-ANTIBODIES; GLYCOPROTEIN SYNTHESIS; RETINOIC ACID AB The polar-planar compound hexamethylene bisacetamide (HMBA) can inhibit HT29 colon carcinoma cell growth and induce a more benign phenotype, as defined by decreased anchorage-independent clonogenicity, loss of a cell surface malignancy marker, and decreased in vivo tumorigenicity. The principle aim of this study was to determine whether HMBA's effects on HT29 cell growth and biologic behavior correlate with effects on intestinal differentiation. Parallel studies were performed with sodium butyrate (NaBT), a potent inducer of intestinal differentiation. HT29 cell growth, proliferation, and markers of intestinal differentiation were assayed after short- and long-term treatment with HMBA, NaBT, or the combination. Both 5 mM HMBA and 5 mM NaBT were potent inhibitors of monolayer growth; in combination their effects were nearly additive. Inhibition of DNA synthesis was detectable within 6 h of treatment and was preceded by down-regulation of c-myc expression. Soft agar clonogenicity was also decreased by 90%, >99%, and >99% by HMBA, NaBT, and the combination, respectively. Despite these parallel effects on growth and in vitro markers of a benign phenotype, effects on intestinal differentiation were discordant. NaBT induced significant increases in membrane-associated alkaline phosphatase activity, cytosolic mucin content, PAS(+)/diastase-resistant cells, and ultrastructural evidence of intestinal cell differentiation. HMBA not only failed to induce markers of intestinal differentiation, but attenuated NaBT's effects when used in combination. These data suggest that growth and intestinal differentiation may be independently regulated in HT29 cells. They also suggest that expression of intestinal markers of differentiation is not a prerequisite for the acquisition of a more benign phenotype. (C) 1994 Wiley-Liss, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROENTEROL UNIT,BOSTON,MA 02118. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DEPT MED,BOSTON,MA 02118. MALLORY INST PATHOL,BOSTON,MA 02118. RP SCHROY, PC (reprint author), BOSTON UNIV,MED CTR,DEPT MED,GASTROENTEROL SECT,BOSTON,MA 02118, USA. FU NCI NIH HHS [K08CA01586] NR 65 TC 54 Z9 54 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD OCT PY 1994 VL 161 IS 1 BP 111 EP 123 DI 10.1002/jcp.1041610114 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA PK530 UT WOS:A1994PK53000013 PM 7929596 ER PT J AU GRINSPOON, SK BILLER, BMK AF GRINSPOON, SK BILLER, BMK TI LABORATORY ASSESSMENT OF ADRENAL INSUFFICIENCY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENOCORTICAL FUNCTION; ACTH TEST; CORTISOL RESPONSE; INSULIN-HYPOGLYCEMIA; PLASMA ACTH; METYRAPONE; AXIS; DYSFUNCTION; STIMULATION C1 MASSACHUSETTS GEN HOSP, NEUROENDOCRINE UNIT, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066] NR 35 TC 313 Z9 319 U1 2 U2 11 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 1994 VL 79 IS 4 BP 923 EP 931 DI 10.1210/jc.79.4.923 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200001 PM 7962298 ER PT J AU GELBERT, L SCHIPANI, E JUPPNER, H ABOUSAMRA, AB SEGRE, GV NAYLOR, S DRABKIN, H HEATH, H AF GELBERT, L SCHIPANI, E JUPPNER, H ABOUSAMRA, AB SEGRE, GV NAYLOR, S DRABKIN, H HEATH, H TI CHROMOSOMAL LOCALIZATION OF THE PARATHYROID-HORMONE PARATHYROID HORMONE-RELATED PROTEIN-RECEPTOR GENE TO HUMAN-CHROMOSOME 3P21.1-P24.2 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PEPTIDE RECEPTOR; CELLS; ACIDS AB The human PTH/PTH-related peptide (PTH/PTHrP) receptor could be involved in hereditary disorders of PTH or PTHrP action. Knowledge of the gene's chromosomal location would allow studies linking it to specific disease traits. Therefore, we mapped the human PTH/PTHrP receptor gene by polymerase chain reaction of human/rodent somatic cell hybrid panels using oligonucleotide primers designed to amplify a portion of the gene from genomic DNA. The PTH/PTHrP gene was unambiguously assigned to the short arm of human chromosome 3, in the region designated 3p21.1-p24.2. Analysis of a second chromosome 3-specific mapping panel suggests that the gene is located near the 3p21.2-p21.3 boundary. The availability of highly polymorphic markers located in this region will permit exploration of the PTH/PTHrP receptor locus in genetic linkage searches for the causes of bone, calcium, and other potential disorders. C1 UNIV UTAH, HLTH SCI CTR, DEPT HUMAN GENET, SALT LAKE CITY, UT 84132 USA. UNIV UTAH, HLTH SCI CTR, HOWARD HUGHES MED INST, SALT LAKE CITY, UT 84132 USA. UNIV UTAH, HLTH SCI CTR, DEPT MED, DIV ENDOCRINOL DIABET & METAB, SALT LAKE CITY, UT 84132 USA. MASSACHUSETTS GEN HOSP, DEPT MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX 78284 USA. UNIV COLORADO, CTR CANC, DENVER, CO 80262 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NHGRI NIH HHS [R01-HG00358]; PHS HHS [R01-38855, R01-46718] NR 14 TC 17 Z9 17 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1994 VL 79 IS 4 BP 1046 EP 1048 DI 10.1210/jc.79.4.1046 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200022 PM 7962272 ER PT J AU HALL, JE MARTIN, KA WHITNEY, HA LANDY, H CROWLEY, WF AF HALL, JE MARTIN, KA WHITNEY, HA LANDY, H CROWLEY, WF TI POTENTIAL FOR FERTILITY WITH REPLACEMENT OF HYPOTHALAMIC GONADOTROPIN-RELEASING-HORMONE IN LONG-TERM FEMALE SURVIVORS OF CRANIAL TUMORS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BRAIN-TUMORS; PITUITARY-FUNCTION; GROWTH-HORMONE; OVULATION; INDUCTION; SECRETION; IRRADIATION; WOMEN; THERAPY; AMENORRHEA AB Dysfunction of the hypothalamic-pituitary axis presenting as hypogonadotropic amenorrhea is a common sequelae of treatment for cranial tumors with surgery and/or radiation. We hypothesized that the site of the defect in this condition is hypothalamic, rather than pituitary, in the majority of patients. Nine women with acquired hypogonadotropic hypogonadism after treatment with transphenoidal pituitary surgery (n = 3), transphenoidal surgery plus conventional radiotherapy (XRT; n = 1), hypothalamic surgery plus XRT (n = 2), or XRT with or without noncentral nervous system surgery (n = 3) underwent assessment of endogenous pulsatile LH secretion and a standard GnRH test followed by iv administration of a physiological replacement regimen of exogenous GnRH. A total of 25 cycles were completed at doses of 75 or 100 ng/kg.bolus. Ovulation occurred in 78% of patients, with all ovulatory patients who desired fertility becoming pregnant. The hormonal responses in these cycles did not differ from the patterns of sex steroids and gonadotropins in normal women. The response to pulsatile GnRH was not influenced by GH deficiency or PRL abnormalities. Of the two patients who failed to ovulate, there was no evidence of folliculogenesis in one, whereas the second consistently developed follicles, but proved incapable of mounting a LH surge despite adequate preovulatory estradiol levels. Both patients had a history of pituitary radiation and surgery. There was no consistent relationship between the results of GnRH testing and the pattern of pulsatile LH secretion. However, the only patient who failed to achieve folliculogenesis was the only patient without a FSH response to GnRH testing and an apulsatile baseline study. Hypothalamic GnRH deficiency is the etiology of hypogonadism in the majority of patients after treatment with hypothalamic or pituitary surgery or cranial irradiation. Therefore, exogenous pulsatile GnRH represents a physiological replacement therapy that completely restores normal gonadotropin dynamics, resulting in ovulation and fertility. C1 MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CTR REPROD ENDOCRINE SCI, DEPT MED, BOSTON, MA 02114 USA. FU FDA HHS [FDU000477]; NICHD NIH HHS [P30 HD028138, T32 HD007396, U54-HD-29164, R01-HD-15080] NR 42 TC 23 Z9 26 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 1994 VL 79 IS 4 BP 1166 EP 1172 DI 10.1210/jc.79.4.1166 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PN872 UT WOS:A1994PN87200044 PM 7962290 ER PT J AU HOTAMISLIGIL, GS BUDAVARI, A MURRAY, D SPIEGELMAN, BM AF HOTAMISLIGIL, GS BUDAVARI, A MURRAY, D SPIEGELMAN, BM TI REDUCED TYROSINE KINASE-ACTIVITY OF THE INSULIN-RECEPTOR IN OBESITY-DIABETES - CENTRAL ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CYTOKINES; METABOLISM; INSULIN ACTION; INSULIN RESISTANCE; NIDDM ID PHOSPHORYLATION; RESISTANCE; ADIPOCYTES; PROTEIN; IRS-1; AUTOPHOSPHORYLATION; SUBSTRATE-1; CANCER; MUSCLE; CELLS AB Insulin resistance is an important metabolic abnormality often associated with infections, cancer, obesity, and especially non-insulin-dependent diabetes mellitus (NIDDM). We have previously demonstrated that tumor necrosis factor-alpha produced by adipose tissue is a key mediator of insulin resistance in animal models of obesity-diabetes. However, the mechanism by which TNF-alpha interferes with insulin action is not known. Since a defective insulin receptor (IR) tyrosine kinase activity has been observed in obesity and NIDDM, we measured the IR tyrosine kinase activity in the Zucker (fa/fa) rat model of obesity and insulin resistance after neutralizing TNF-alpha with a soluble TNF receptor (TNFR)-IgG fusion protein. This neutralization resulted in a marked increase in insulin-stimulated autophosphorylation of the IR, as well as phosphorylation of insulin receptor substrate 1 (IRS-1) in muscle and fat tissues of the fa/fa rats, restoring them to near control (lean) levels. In contrast, no significant changes were observed in insulin-stimulated tyrosine phosphorylations of IR and IRS-1 in liver. The physiological significance of the improvements in IR signaling was indicated by a concurrent reduction in plasma glucose, insulin, and free fatty acid levels, These results demonstrate that TNP-alpha participates in obesity-related systemic insulin resistance by inhibiting the IR tyrosine kinase in the two tissues mainly responsible for insulin-stimulated glucose uptake: muscle and fat. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-42539] NR 30 TC 546 Z9 562 U1 1 U2 17 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 1994 VL 94 IS 4 BP 1543 EP 1549 DI 10.1172/JCI117495 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PK185 UT WOS:A1994PK18500029 PM 7523453 ER PT J AU JORGENSEN, JH SWENSON, JM TENOVER, FC FERRARO, MJ HINDLER, JA MURRAY, PR AF JORGENSEN, JH SWENSON, JM TENOVER, FC FERRARO, MJ HINDLER, JA MURRAY, PR TI DEVELOPMENT OF INTERPRETIVE CRITERIA AND QUALITY-CONTROL LIMITS FOR BROTH MICRODILUTION AND DISK DIFFUSION ANTIMICROBIAL SUSCEPTIBILITY TESTING OF STREPTOCOCCUS-PNEUMONIAE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HAEMOPHILUS TEST MEDIUM; PENICILLIN-RESISTANT; UNITED-STATES; PNEUMOCOCCAL MENINGITIS; THERAPY; ANTIBIOTICS; CEFOTAXIME; DIAGNOSIS; FAILURE; CHLORAMPHENICOL AB A five-center collaborative study was undertaken to develop quality control and specific interpretive criteria for susceptibility testing of Streptococcus pneumoniae against 12 antimicrobial agents. MICs were determined for 248 pneumococcal clinical isolates (with an emphasis on resistant strains) by use of the National Committee for Clinical Laboratory Standards (NCCLS)-recommended broth microdilution procedure incorporating lysed horse blood-supplemented Mueller-Hinton broth. NCCLS disk diffusion testing was also performed for each isolate by using Mueller-Hinton sheep blood agar incubated in 5% CO2. Repetitive testing of S. pneumoniae ATCC 49619 with different sources and lots of media and disks allowed development of quality control ranges which encompassed approximately 95% of MIC and zone size values observed in the study. Good intra- and interlaboratory reproducibilities were seen with these testing methods and all of the drugs examined. On the basis of the results of this study, MIC interpretive criteria are proposed for II agents. Comparisons of MICs and disk diffusion zone sizes allowed disk diffusion zone size interpretive criteria to be proposed for five drugs and confirmed the use of the oxacillin disk test for prediction of penicillin susceptibility among pneumococci. Excessive numbers of minor-category interpretive errors precludes recommendation at this time of the disk diffusion method for testing of pneumococci against five of the drugs. Use of these proposed quality control and interpretive criteria should provide for reproducible test results and allow recognition of recently emerging resistance among pneumococcal clinical isolates. C1 CTR DIS CONTROL & PREVENT,NOSOCOMIAL PATHOGENS BRANCH,ATLANTA,GA 30341. MASSACHUSETTS GEN HOSP,MICROBIOL LAB,BOSTON,MA 02114. UNIV CALIF LOS ANGELES,MED CTR,MICROBIOL LAB,LOS ANGELES,CA 90024. WASHINGTON UNIV,MED CTR,DEPT LAB MED,ST LOUIS,MO. RP JORGENSEN, JH (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284, USA. NR 48 TC 53 Z9 53 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1994 VL 32 IS 10 BP 2448 EP 2459 PG 12 WC Microbiology SC Microbiology GA PG912 UT WOS:A1994PG91200020 PM 7814481 ER PT J AU BARCHIESI, F COLOMBO, AL MCGOUGH, DA RINALDI, MG AF BARCHIESI, F COLOMBO, AL MCGOUGH, DA RINALDI, MG TI COMPARATIVE-STUDY OF BROTH MACRODILUTION AND MICRODILUTION TECHNIQUES FOR IN-VITRO ANTIFUNGAL SUSCEPTIBILITY TESTING OF YEASTS BY USING THE NATIONAL-COMMITTEE-FOR-CLINICAL-LABORATORY-STANDARDS PROPOSED STANDARD SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FLUCONAZOLE-RESISTANT CANDIDA; HUMAN-IMMUNODEFICIENCY-VIRUS; INOCULUM SIZE; INVITRO SUSCEPTIBILITIES; CRYPTOCOCCUS-NEOFORMANS; MULTICENTER EVALUATION; IN-VITRO; ALBICANS; AIDS; TRIAZOLE AB A comparative study of broth macro- and microdilution methods for susceptibility testing of fluconazole, itraconazole, flucytosine, and amphotericin B was conducted with 273 yeasts. The clinical isolates included 100 Candida albicans, 28 Candida tropicalis, 25 Candida parapsilosis, 15 Candida lusitaniae, 15 Candida krusei, 50 Cryptococcus neoformans var. neoformans, 25 Torulopsis (Candida) glabrata, and 15 Trichosporon beigelii strains. Both methods were performed according to the National Committee for Clinical Laboratory Standards' (NCCLS) recommendations (document M27-P). For fluconazole, itraconazole, and flucytosine, the endpoint was the tube that showed 80% growth inhibition compared,vith the growth control for the macrodilution method and the well with slightly hazy turbidity (score I) compared with the growth control for the microdilution method. For amphotericin B, the endpoint was the tube and/or well in which there was absence of growth. For the reference macrodilution method, the MICs were determined after 48 h of incubation for Candida spp., T. glabrata, and T. beigelii and after 72 h for C. neoformans var. neoformans. For the microdilution method, either the first-day MICs (24 h for all isolates other than C. neoformans var. neoformans and 48 h for C. neoformans var. neoformans) or the second-day MICs (48 and 72 h, respectively) were evaluated. The agreement within one doubling dilution of the macrodilution reference for all drugs,vas higher with the second-day MICs than with the first-day MICs for the microdilution test for most of the tested strains. General agreement was 92% for fluconazole, 85.7% for itraconazole, 98.3% for flucytosine, and 96.4% for amphotericin B. For C. neoformans var. neoformans and T. beigelii, the agreement of the first-day reading was higher than that of the second-day reading for fluconazole (94 versus 92%, respectively, for C. neoformans var. neoformans, and 86.7 versus 80%, respectively, for T. beigelii). Our studies indicate that the microdilution technique performed following the NCCLS guidelines with a second-day reading is a valid alternative method for testing fluconazole, itraconazole, flucytosine, and amphotericin B against these eight species of yeasts. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV ANCONA,IST MALATTIE INFETT & MED PUBL,ANCONA,ITALY. ESCOLA PAULISTA MED,BR-04023 SAO PAULO,BRAZIL. 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 40 TC 91 Z9 94 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 1994 VL 32 IS 10 BP 2494 EP 2500 PG 7 WC Microbiology SC Microbiology GA PG912 UT WOS:A1994PG91200028 PM 7814488 ER PT J AU SAPICO, FL REEVES, D WEXLER, HM DUNCAN, J WILSON, KH FINEGOLD, SM AF SAPICO, FL REEVES, D WEXLER, HM DUNCAN, J WILSON, KH FINEGOLD, SM TI PRELIMINARY-STUDY USING SPECIES-SPECIFIC OLIGONUCLEOTIDE PROBE FOR RIBOSOMAL-RNA OF BILOPHILA-WADSWORTHIA SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL DNA; SPECIMENS; RNA AB Portions of the 16S RNA from a urease-positive Bilophila wadsworthia strain were sequenced, and a probe was constructed. The probe was end labeled with [P-32]ATP and polynucleotide kinase and hybridized on a nylon filter (by dot blot hybridization) to the immobilized rRNA of 12 B. wadsworthia strains and eight other anaerobic isolates. The probe efficiently?v hybridized only to the Bilophila strains. Cross-reactivity at high RNA levels (2,000 ng) was observed with one strain of Bacteroides thetaiotaomicron and one strain of Bacteroides fragilis (with 10X SET buffer [20x SET buffer is 0.5 M NaCl, 0.03 M Tris, and 2 mM EDTA]) but was not seen at lower RNA levels or with 5x SET buffer. When tested against mixed cultures of aerobic and anaerobic isolates representative of appendiceal abscess flora, the probe did not react with mixed cultures containing no Bilophila cells and could detect greater than or equal to 10(5) Bilophila CFU/ml when the mixture was seeded with Bilophila cells. This probe is of potential use in the rapid identification of pure isolates and in the direct identification of B. wadsworthia in clinical specimens. C1 W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,MED SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. UNIV SO CALIF,RANCHO LOS AMIGOS MED CTR,DEPT MED,DOWNEY,CA 90242. UNIV SO CALIF,SCH MED,DEPT MED,LOS ANGELES,CA 90033. VET AFFAIRS MED CTR,DIV INFECT DIS,DURHAM,NC 27705. VET AFFAIRS MED CTR,MED SERV,DURHAM,NC 27705. VET AFFAIRS MED CTR,RES SERV,DURHAM,NC 27705. DUKE UNIV,MED CTR,DURHAM,NC 27705. RP SAPICO, FL (reprint author), UNIV SO CALIF,RANCHO LOS AMIGOS MED CTR,DIV INFECT DIS,7601 E IMPERIAL HWY,244 HB,DOWNEY,CA 90242, USA. NR 22 TC 14 Z9 14 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 1994 VL 32 IS 10 BP 2510 EP 2513 PG 4 WC Microbiology SC Microbiology GA PG912 UT WOS:A1994PG91200031 PM 7529241 ER PT J AU FINE, HA AF FINE, HA TI BRAIN-TUMOR CHEMOTHERAPY TRIALS - SLOW START, BUT QUICKLY GAINING SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID PROGNOSTIC FACTORS; MALIGNANT GLIOMA; CRITERIA RP FINE, HA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT PY 1994 VL 12 IS 10 BP 2003 EP 2004 PG 2 WC Oncology SC Oncology GA PL363 UT WOS:A1994PL36300002 PM 7931468 ER PT J AU OROURKE, DA WURTMAN, JJ WURTMAN, RJ TSAY, R GLEASON, R BAER, L JENIKE, MA AF OROURKE, DA WURTMAN, JJ WURTMAN, RJ TSAY, R GLEASON, R BAER, L JENIKE, MA TI ABERRANT SNACKING PATTERNS AND EATING DISORDERS IN PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID D-FENFLURAMINE; FLUOXETINE; TRIAL AB Background: Appetitive symptoms, particularly carbohydrate craving, have been shown to occur in patients whose conditions responded to treatment with drugs that enhance serotonin-mediated neurotransmission. This suggested that patients with obsessive compulsive disorder (OCD) who also frequently respond to serotonergic drugs also might have similar distributions of appetitive and eating patterns. Method: A survey study of 170 OCD patients and 920 controls was conducted using a questionnaire that inquired about snacking behavior, including food preference, mood changes after eating, and previous diagnosis of eating disorders. The frequency responses in the two groups were tested for statistical significance. Results: Significant differences were found between the OCD and control groups with respect to the reported incidence of eating disorders, snacking patterns, and mood response to food. Conclusion: This finding of different snacking patterns in OCD mirrors that found in other disorders that have been shown to be responsive to serotonergic drugs. The high incidence of carbohydrate snacking among OCD patients compared with the control group provides additional evidence that brain serotonin may be involved in this disorder. C1 MIT, CLIN RES CTR, 45 CARLETON ST, BLDG E25-604, CAMBRIDGE, MA 02139 USA. HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02115 USA. NR 12 TC 6 Z9 6 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 1994 VL 55 IS 10 BP 445 EP 447 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PW028 UT WOS:A1994PW02800005 PM 7961522 ER PT J AU CHEN, WJ FARAONE, SV BIEDERMAN, J TSUANG, MT AF CHEN, WJ FARAONE, SV BIEDERMAN, J TSUANG, MT TI DIAGNOSTIC-ACCURACY OF THE CHILD-BEHAVIOR CHECKLIST SCALES FOR ATTENTION-DEFICIT HYPERACTIVITY DISORDER - A RECEIVER-OPERATING CHARACTERISTIC ANALYSIS SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID FAMILIAL ASSOCIATION; RISK-FACTORS; COMORBIDITY; PSYCHOPATHOLOGY; CONVERGENCE; RELATIVES; CRITERIA; ANXIETY; CURVE AB The diagnostic accuracy of the Child Behavior Checklist (CBCL) scales for attention-deficit hyperactivity disorder (ADHD) were examined using receiver-operating characteristic (ROC) analysis. Three logistic regression models were estimated in an initial sample of 121 children with and without ADHD. These models were then tested in a cross-validation sample (N = 122) and among the 111 brothers and 108 sisters of the initial and cross-validation samples. In all four groups, the CBCL Attention Problems scale had the highest discriminating power for ADHD. Adding other scales did not increase the area under the curve of the ROC significantly. These findings suggest that the CBCL Attention Problems scale could serve as a rapid and useful screening instrument not only to help identify cases likely to meet criteria for ADHD in clinical settings but also to identify cases of ADHD among the siblings of children with ADHD. C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,FRUIT ST,BOSTON,MA 02114. NATL TAIWAN UNIV,COLL MED,INST PUBL HLTH,TAIPEI,TAIWAN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. OI Faraone, Stephen/0000-0002-9217-3982 NR 33 TC 200 Z9 202 U1 4 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 1994 VL 62 IS 5 BP 1017 EP 1025 DI 10.1037/0022-006X.62.5.1017 PG 9 WC Psychology, Clinical SC Psychology GA PM869 UT WOS:A1994PM86900018 PM 7806710 ER PT J AU TSOMIDES, TJ ALDOVINI, A JOHNSON, RP WALKER, BD YOUNG, RA EISEN, HN AF TSOMIDES, TJ ALDOVINI, A JOHNSON, RP WALKER, BD YOUNG, RA EISEN, HN TI NATURALLY PROCESSED VIRAL PEPTIDES RECOGNIZED BY CYTOTOXIC T-LYMPHOCYTES ON CELLS CHRONICALLY INFECTED BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTO-TOXIC RESPONSES; EPSTEIN-BARR-VIRUS; CLASS-I MOLECULES; PERIPHERAL-BLOOD; SEROPOSITIVE INDIVIDUALS; REVERSE-TRANSCRIPTASE; FINE SPECIFICITY; EFFECTOR-CELLS; HIV-1 AB We have established long-term cultures of several cell lines stably and uniformly expressing human immunodeficiency virus type 1 (HIV-1) in order to (a) identify naturally processed HIV-1 peptides recognized by cytotoxic T lymphocytes (CTL) from HIV-1-seropositive individuals and (b) consider the hypothesis that naturally occurring epitope densities on HIV-infected cells may limit their lysis by CTL. Each of two A2-restricted CD8(+) CTL specific for HIV-1 gag or reverse transcriptase (RT) recognized a single naturally processed HIV-1 peptide in trifluoroacetic acid (TEA) extracts of infected cells: gag 77-85 (SLYNTVATL) or RT 476-484 (ILKEPVHGV). Both processed peptides match the synthetic peptides that are optimally active in cytotoxicity assays and have the consensus motif described for A2-associated peptides. Their abundances were approximate to 400 and approximate to 12 molecules per infected Jurkat-A2 cell, respectively. Other synthetic HIV-1 peptides active at subnanomolar concentrations were not present in infected cells. Except for the antigen processing mutant line T2, HIV-infected HLA-A2(+) cell lines were specifically lysed by both A2-restricted CTL, although infected Jurkat-A2 cells were lysed more poorly by RT-specific CTL than by gag-specific CTL, suggesting that low cell surface density of a natural peptide may limit the effectiveness of some HIV-specific CTL despite their vigorous activity against synthetic peptide-treated target cells. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. MIT,WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02142. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP TSOMIDES, TJ (reprint author), MIT E17128,CTR CANC RES,77 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. RI Young, Richard/F-6495-2012 OI Young, Richard/0000-0001-8855-8647 FU NCI NIH HHS [R35 CA-42504]; NIAID NIH HHS [AI-26463, AI-34247] NR 67 TC 201 Z9 203 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 1 PY 1994 VL 180 IS 4 BP 1283 EP 1293 DI 10.1084/jem.180.4.1283 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PJ703 UT WOS:A1994PJ70300012 PM 7523570 ER PT J AU JENIKE, MA AF JENIKE, MA TI ELECTROCONVULSIVE-THERAPY IN THE ELDERLY - A CONTROLLED TRIAL SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. NR 4 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-DEC PY 1994 VL 7 IS 4 BP 257 EP 257 PG 1 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA QL410 UT WOS:A1994QL41000013 ER PT J AU UMLAS, ME BISCHOFF, RJ GELBERMAN, RH AF UMLAS, ME BISCHOFF, RJ GELBERMAN, RH TI PREDICTORS OF NEUROVASCULAR DISPLACEMENT IN HANDS WITH DUPUYTRENS CONTRACTURE SO JOURNAL OF HAND SURGERY-BRITISH AND EUROPEAN VOLUME LA English DT Article AB A prospective study of hands with Dupuytren's contracture was designed to test the association of three variables, the presence of an interdigital soft tissue mass, the presence of flexion contractures at each digital joint, and the duration of contracture, with the formation of spiral nerves. 66 digits in 37 hands affected by Dupuytren's disease were examined intra-operatively. Of the 34 digits (52%) with spiral nerves, 28 had soft tissue masses (42%). The sensitivity of a soft tissue mass alone as a predictor of a spiral nerve was 59% and the specificity 75%. The presence of a flexion contracture at the PIP joint had a sensitivity of 88% and a specificity of 62% for the presence of a spiral nerve. The combination of a soft tissue mass and a PIP joint contracture was a very specific (93%) but not a particularly sensitive (50%) test for spiral nerve formation. The formation of a spiral nerve is progressive, occurring most often in hands with significant PIP joint contractures with or without soft tissue interdigital masses. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. NR 0 TC 5 Z9 5 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0266-7681 J9 J HAND SURG-BRIT EUR JI J. Hand Surg.-Br. Eur. Vol. PD OCT PY 1994 VL 19B IS 5 BP 664 EP 666 DI 10.1016/0266-7681(94)90140-6 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PJ652 UT WOS:A1994PJ65200030 PM 7822934 ER PT J AU XU, YH SLAYTER, HS AF XU, YH SLAYTER, HS TI IMMUNOCYTOCHEMICAL LOCALIZATION OF ENDOGENOUS ANTI-THROMBIN-III IN THE VASCULATURE OF RAT-TISSUES REVEALS LOCATIONS OF ANTICOAGULANTLY ACTIVE HEPARAN-SULFATE PROTEOGLYCANS SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE ANTI-THROMBIN III; CRYOULTRAMICROTOMY; IMMUNOCYTOCHEMISTRY; ELECTRON MICROSCOPY; HEPARAN SULFATE PROTEOGLYCANS; ANTICOAGULATION; RAT VASCULATURE ID CULTURED ENDOTHELIAL-CELLS; RABBIT ANTITHROMBIN-III; BASEMENT-MEMBRANE; HEPARINLIKE MOLECULES; PROTEOHEPARAN SULFATE; INVIVO BEHAVIOR; AORTA INVITRO; PROTEINS; SURFACE; MUSCLE AB We localized endogenous anti-thrombin III (ATIII) by light and electron microscopic immunocytochemical staining in cryostat and ultra-thin frozen sections of 10 different rat tissues, using rabbit alpha-human ATIII antibody that was shown to crossreact strongly with rat ATIII. EM immunocytochemical methods revealed discrete deposits of endogenous ATIII (absent after heparinase treatment), and thus by inference anticoagulantly active heparan sulfate proteoglycans (HSPGs) at a resolution of 10-20 nm, or an order of magnitude better than autoradiography or LM. ATIII was found in variable amounts almost entirely in the subendothelial space of blood vessels in various rat tissues. In kidney, ATIII was found immediately beneath the endothelium, in concentrated dusters associated with the vascular basement membrane. Equally important is the observed variation in expression of ATIII in the various tissues studied (i.e., kidney > liver, aorta, lung, spleen, adrenal > intestine, muscle, brain). On the basis of these observations, we confirm a model in which vascular abluminal and, perhaps to a much smaller extent, luminal anticoagulantly active HSPGs regulate coagulation mechanism activity, either by serving as a reserve of anticoagulant or by modulating the ambient function of the coagulation cascade.- C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,ELECTRON MICROSCOPY & STRUCT MOLEC BIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL33014] NR 58 TC 25 Z9 25 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD OCT PY 1994 VL 42 IS 10 BP 1365 EP 1376 PG 12 WC Cell Biology SC Cell Biology GA PJ687 UT WOS:A1994PJ68700009 PM 7930519 ER PT J AU SPARANO, JA FISHER, RI WEISS, GR MARGOLIN, K ARONSON, FR HAWKINS, MJ ATKINS, MB DUTCHER, JP GAYNOR, ER BOLDT, DH DOROSHOW, JH ERNEST, ML SZNOL, M MIER, JW AF SPARANO, JA FISHER, RI WEISS, GR MARGOLIN, K ARONSON, FR HAWKINS, MJ ATKINS, MB DUTCHER, JP GAYNOR, ER BOLDT, DH DOROSHOW, JH ERNEST, ML SZNOL, M MIER, JW TI PHASE-II TRIALS OF HIGH-DOSE INTERLEUKIN-2 AND LYMPHOKINE-ACTIVATED KILLER-CELLS IN ADVANCED BREAST-CARCINOMA AND CARCINOMA OF THE LUNG, OVARY, AND PANCREAS AND OTHER TUMORS SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE INTERLEUKIN-2; LAK CELLS; ADVANCED CARCINOMA; BREAST CARCINOMA; PHASE II TRIAL ID NECROSIS-FACTOR-ALPHA; NON-HODGKINS-LYMPHOMA; RECOMBINANT INTERLEUKIN-2; ADVANCED CANCER; ADOPTIVE IMMUNOTHERAPY; CONTINUOUS-INFUSION; THERAPY; COMBINATION; HEAD; NECK AB Treatment with interleukin-2 (IL-2) used alone or in combination with lymphokine-activated killer (LAK) cells is known to be an active therapy for patients with advanced renal cell carcinoma and melanoma. To further explore the activity of IL-2/LAK cell therapy in patients with advanced cancer of various primary sites, the Extramural IL-2/LAK Working Group (ILWG) initiated two phase II trials of high-dose IL-2/LAK therapy: one in patients with advanced breast carcinoma, and one in patients with advanced cancer arising in other sites. Patients with advanced renal cell carcinoma, melanoma, colorectal carcinoma, and lymphoma (Hodgkin's and B-cell non-Hodgkin's) were not eligible for the latter trial, but were treated on other ILWG trials that have been reported previously. Sixty-nine patients received high-dose IL-2 (600,000 IU/kg administered by a 15-min intravenous infusion every 8 h) on days 1-5 and days 11-15. Leukapheresis was performed for collection and ex vivo expansion of LAK cells on days 7-10, and the LAK cells were reinfused on days 11, 12, and 14. The studies were designed to determine whether treatment with IL-2/LAK resulted in at least a 40% response rate, a level of activity that was believed to be sufficient to justify the toxicity and cost of IL-2/LAK therapy. An adequate number of patients with carcinoma of the breast (N = 12), pancreas (N = 8), ovary (N = 7), and lung (non-small cell; N = 6) were accrued to assess response; most of these patients had prior chemotherapy that had failed. In addition, 32 patients with a variety of other tumor types were accrued, but accrual was not adequate to assess response in other primary tumor sites. One patient with adenocarcinoma of the breast had a partial response of 17 weeks' duration. Two patients had minor tumor regression (adenocarcinoma of the lung and spindle cell sarcoma of the lung). We conclude that high-dose IL-2/LAK is not likely to be associated with a response rate exceeding 40% for patients with carcinomas arising in the breast, pancreas, ovary, and lung (non-small cell). C1 LOYOLA UNIV,MED CTR,MAYWOOD,IL. UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. CITY HOPE NATL MED CTR,DUARTE,CA. UNIV CALIF SAN FRANCISCO,MED CTR,SAN FRANCISCO,CA. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA. RP SPARANO, JA (reprint author), ALBERT EINSTEIN COLL MED,MONTEFIORE MED CTR,CTR CANC,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [N01-CM73704, N01-CM73702, N01-CM73703] NR 53 TC 21 Z9 21 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 1994 VL 16 IS 3 BP 216 EP 223 DI 10.1097/00002371-199410000-00006 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA PM631 UT WOS:A1994PM63100006 PM 7834121 ER PT J AU STERN, RS ABEL, E KOO, J EPSTEIN, JH WOLF, J NIGRA, TP VOORHEES, J ANDERSON, TF PRYSTOWSKY, J MULLER, S TAYLOR, JR HERBST, J URBACH, F ARNDT, KA BAUGHMAN, RD BRAVERMAN, IM MURRAY, J PETROZZI, J GONZALEZ, E PARRISH, JA FITZPATRICK, TB FITZGERALD, EJ LANGE, R BLEICH, HL AF STERN, RS ABEL, E KOO, J EPSTEIN, JH WOLF, J NIGRA, TP VOORHEES, J ANDERSON, TF PRYSTOWSKY, J MULLER, S TAYLOR, JR HERBST, J URBACH, F ARNDT, KA BAUGHMAN, RD BRAVERMAN, IM MURRAY, J PETROZZI, J GONZALEZ, E PARRISH, JA FITZPATRICK, TB FITZGERALD, EJ LANGE, R BLEICH, HL TI OCULAR LENS FINDINGS IN PATIENTS TREATED WITH PUVA SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE PSORIASIS; PUVA THERAPY; CATARACT; OCULAR LENS ID ORAL METHOXSALEN PHOTOCHEMOTHERAPY; 8-METHOXYPSORALEN; PSORIASIS; CATARACTS; THERAPY; TRIAL AB In some animal species, exposure of the ocular lens to 8-methoxypsoralen (8-MOP) and ultraviolet-A radiation (PUVA) induces lens opacities. Case reports have suggested that PUVA therapy in humans may be associated with an increased risk of ocular lens abnormalities. To examine this risk, we compared the results of the initial and final examinations, which were performed on an average of 10 years apart in 1,235 individuals enrolled in the PUVA Follow-up Study. After adjustment for age and sex, there was no significant relation between the risk of developing an ocular lens abnormality or cataract and the level of exposure to PUVA. A higher incidence of cataract was noted, however, in the PUVA cohort compared to a large population-based study. In addition, rates of cataract extraction were significantly higher among male members of the PUVA study compared to enrollees in the Physician Health Study. Overall, our data strongly argue against a dose-dependent increase in the risk of cataract or other lens abnormality in association with PUVA therapy in a cohort most of whose members we believe usually used recommended eye protection. Our data do not explain the higher incidence and prevalence of ocular lens pathology in our cohort compared to groups without psoriasis. These differences could reflect differences in criteria for defining these abnormalities, other exposures, or PUVA. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. STANFORD UNIV,SCH MED,STANFORD,CA. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA. BAYLOR COLL MED,HOUSTON,TX 77030. WASHINGTON HOSP CTR,WASHINGTON,DC 20010. UNIV MICHIGAN,SCH MED,ANN ARBOR,MI 48109. COLUMBIA UNIV,COLL PHYS & SURG,NEW YORK,NY 10027. MAYO CLIN & MAYO GRAD SCH MED,ROCHESTER,MN 55901. UNIV MIAMI,MIAMI,FL. MT SINAI MED CTR,NEW YORK,NY 10029. TEMPLE UNIV,SCH MED,PHILADELPHIA,PA. BETH ISRAEL HOSP,BOSTON,MA 02215. DARTMOUTH COLL,SCH MED,HANOVER,NH 03755. YALE UNIV,SCH MED,NEW HAVEN,CT 06520. DUKE UNIV,MED CTR,DURHAM,NC 27706. HOSP UNIV PENN,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,BOSTON,MA. RP STERN, RS (reprint author), BETH ISRAEL HOSP,DEPT DERMATOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIADDK NIH HHS [1-AM-2252] NR 25 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1994 VL 103 IS 4 BP 534 EP 538 DI 10.1111/1523-1747.ep12395733 PG 5 WC Dermatology SC Dermatology GA PL698 UT WOS:A1994PL69800014 PM 7930678 ER PT J AU MAYTIN, EV WIMBERLY, JM KANE, KS AF MAYTIN, EV WIMBERLY, JM KANE, KS TI HEAT-SHOCK MODULATES UVB-INDUCED CELL-DEATH IN HUMAN EPIDERMAL-KERATINOCYTES - EVIDENCE FOR A HYPERTHERMIA-INDUCIBLE PROTECTIVE RESPONSE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE ULTRAVIOLET RAYS; CELL DEATH; APOPTOSIS; STRESS RESPONSE ID HUMAN-SKIN FIBROBLASTS; MESSENGER-RNA; DNA FRAGMENTATION; ULTRAVIOLET-IRRADIATION; GENE-EXPRESSION; STRESS PROTEIN; CYTO-TOXICITY; SUNBURN CELL; INDUCTION; APOPTOSIS AB The ability of heat shock to induce functional protection against ultraviolet B (UVB) light was examined in keratinocytes cultured from human skin. Cell death, measured with fluorescent vital dyes, increased in a UVB dose-dependent manner (LD(50)similar to 20-60 mJ/cm(2)). However, a 60-min heat shock at 40 degrees C or 42 degrees C, administered several hours before UVB irradiation, reduced cell death by 2.0-2.5 times. Inducible protection took time to develop, with an optimal interval of similar to 6 h between beat and UVB exposures. Heat-inducible protection was completely blocked if either cordy-cepin (3'-deoxyadenosine), to inhibit mRNA synthesis, or cycloheximide, to inhibit protein synthesis, were present during the heating period. To determine whether apoptosis might be involved in UVB-induced keratinocyte death in this system, evidence for endonuclease activity was sought via in situ enzymatic labeling with terminal deoxynucleotidyl transferase and biotinylated-dUTP. Labeled nuclei were detected in UVB-irradiated cultures, and heat pretreatment at 6 h prior to UVB exposure (< 60 mJ/cm(2)) resulted in a 50% reduction in labeled nuclei. Overall, the data show that UVB-induced cell death in human keratinocyte cultures is attenuated by a heat-inducible mechanism that requires ongoing synthesis of mRNA and protein. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. FU NIAMS NIH HHS [5T32AR07098] NR 51 TC 52 Z9 53 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1994 VL 103 IS 4 BP 547 EP 553 DI 10.1111/1523-1747.ep12396274 PG 7 WC Dermatology SC Dermatology GA PL698 UT WOS:A1994PL69800017 PM 7930680 ER PT J AU SCHWARZSCHILD, MA DAUER, WT LEWIS, SE HAMILL, LK FINK, JS HYMAN, SE AF SCHWARZSCHILD, MA DAUER, WT LEWIS, SE HAMILL, LK FINK, JS HYMAN, SE TI LEUKEMIA INHIBITORY FACTOR AND CILIARY NEUROTROPHIC FACTOR INCREASE ACTIVATED RAS IN A NEUROBLASTOMA CELL-LINE AND IN SYMPATHETIC NEURON CULTURES SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE RAS; LEUKEMIA INHIBITORY FACTOR; CILIARY NEUROTROPHIC FACTOR; ONCOSTATIN M; NEUROBLASTOMA; SYMPATHETIC NEURONS; TYROSINE PHOSPHORYLATION; GP130 ID NERVE GROWTH-FACTOR; TYROSINE KINASE-ACTIVITY; IL-6 SIGNAL TRANSDUCER; PHEOCHROMOCYTOMA PC12 CELLS; COLONY-STIMULATING FACTOR; ONCOSTATIN-M; DIFFERENTIATION FACTOR; RECEPTOR COMPONENT; P21RAS ACTIVATION; INTERLEUKIN-6 AB The cytokines leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) have been implicated in determination of neuronal phenotype as well as promotion of neuronal survival. However, the intracellular mechanisms by which their signals are transduced remain poorly understood. We have previously studied the regulation of vasoactive intestinal polypeptide gene expression by LIF and CNTF in the NBFL neuroblastoma cell line. Because these cytokines induce tyrosine phosphorylation that may lead to Ras activation, we explored a possible role for Ras in LIF- and CNTF-induced signal transduction. In NBFL cells LIF increases activated Ras in a rapid, transient, and concentration-dependent manner. CNTF and a related cytokine, oncostatin M, produce similar increases. CNTF and LIF also increase activated Ras in neuron-enriched dissociated cultures of sympathetic ganglia. Moreover, these cytokines rapidly and transiently induce specific tyrosine-phosphorylated proteins, p165 and p195. The protein kinase inhibitors K252a and staurosporine block LIF-induced increases in tyrosine phosphorylalion, activated Ras, and vasoactive intestinal polypeptide mRNA in NBFL cells. These data support a possible role for Ras in the cell differentiation effects of LIF and CNTF. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROBIOL LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NIMH NIH HHS [MH00892]; NINDS NIH HHS [NS27514, NS29767] NR 58 TC 19 Z9 20 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 OCT PY 1994 VL 63 IS 4 BP 1246 EP 1254 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PH202 UT WOS:A1994PH20200007 PM 7523587 ER PT J AU ROEDER, T NATHANSON, JA AF ROEDER, T NATHANSON, JA TI PHOTOAFFINITY-LABELING OF A NEURONAL OCTOPAMINE RECEPTOR SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE OCTOPAMINE; SCHISTOCERCA GREGARIA; RECEPTOR PROTEIN; PHOTOAFFINITY LIGAND; 2(2,6-DIETHYL-4-AZIDOPHENYLIMINO)IMIDAZOLIDINE; INSECT ID SENSITIVE ADENYLATE-CYCLASE; LOCUST NERVOUS-TISSUE; POTENT; AGONISTS; DROSOPHILA; MIGRATORIA; SUBTYPES; BINDING; INSECTS AB The invertebrate aminergic neurotransmitter and neuromodulator octopamine (OA) acts at both neuronal and nonneuronal receptors that appear to have distinct pharmacological characteristics. The current work uses a potent and specific OA photoaffinity ligand, tritiated 2(2,6-diethyl-4-azidophenylimino)imidazo ([H-3]NC-5Z), to identify and characterize a putative neuronal OA receptor protein in membranes from nerve tissue of the desert locust, Schistocerca gregaria. Under nonphotolyzing conditions, [H-3]NC-5Z demonstrated high-affinity binding (K-D = 2.5 +/- 0.3 nM; B-max = 702 fmol/mg mg of protein) to a single class of noninteracting sites. The absolute and rank order potency of binding of both agonists and antagonists was highly correlated (r = 0.99) with their known ability to displace [H-3]OA binding to locust neuronal membranes and was consistent with the labeling of a class 3 OA receptor. Under photolyzing conditions, [H-3]NC-5Z demonstrated irreversible binding that was resistant to trichloroacetic acid and methanol, displaceable by OA and other octopaminergic agonists and antagonists, soluble in sodium dodecyl sulfate, and only sparingly soluble in nonionic detergents. Membrane-bound [H-3]NC-5Z, solubilized with Nonidet P-40, bound specifically only to immobilized concanavalin A or lentil lectin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of photolyzed proteins under reducing conditions revealed a single peak of radioactivity with a molecular mass of 53 +/- 5 kDa. Taken together, these biochemical and pharmacological results support the identity of this protein peak as that of the neuronal OA3 receptor. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPHARMACOL RES LAB,BOSTON,MA 02114. RP ROEDER, T (reprint author), UNIV HAMBURG,INST ZOOL,MARTIN LUTHER KING PL 3,W-2000 HAMBURG 13,GERMANY. RI Roeder, Thomas/B-9016-2011 OI Roeder, Thomas/0000-0002-3489-3834 FU NIAID NIH HHS [AI 29533] NR 34 TC 7 Z9 7 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 OCT PY 1994 VL 63 IS 4 BP 1516 EP 1521 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PH202 UT WOS:A1994PH20200041 PM 7931305 ER PT J AU CONRAD, AJ CHIANG, EY ANDEEN, LE AVOLIO, C WALKER, SM BAUMHEFNER, RW MIRZAYAN, R TOURTELLOTTE, WW AF CONRAD, AJ CHIANG, EY ANDEEN, LE AVOLIO, C WALKER, SM BAUMHEFNER, RW MIRZAYAN, R TOURTELLOTTE, WW TI QUANTITATION OF INTRATHECAL MEASLES-VIRUS IGG ANTIBODY-SYNTHESIS RATE - SUBACUTE SCLEROSING PANENCEPHALITIS AND MULTIPLE-SCLEROSIS SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE MEASLES; SUBACUTE SCLEROSING PANENCEPHALITIS; MULTIPLE SCLEROSIS; INTRATHECAL SYNTHESIS RATE; ANTIBODY INDEX; ENZYME-LINKED IMMUNOSORBENT ASSAY; QUANTITATION; IMMUNOGLOBULIN G ID CENTRAL NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; CEREBROSPINAL-FLUID; HIV ANTIBODIES; AIDS; QUANTIFICATION; ENCEPHALITIS; MENINGITIS; INFECTION; DIAGNOSIS AB A method for quantitating specific anti-viral antibodies in serum and cerebrospinal fluid (CSF) is established using enzyme-linked immunosorbent assay (ELISA). Quantitated antibody levels are used to determine intrathecal specific IgG synthesis rate for the particular antibody. Measles virus was used as a model for validating this quantitative technique: a mutated form of measles virus is a cause of subacute sclerosing panencephalitis (SSPE) and there is a possibility that measles virus is related to the cause of multiple sclerosis (MS). Matched serum and CSF samples were assayed. Concentration of anti-measles IgG was determined and intrathecal measles-specific IgG synthesis rate was calculated. For the SSPE samples, measles-specific IgG synthesis rate was elevated and comprised > 20% of the total intrathecal IgG synthesis rate; these results are consistent with the literature. The ELISA method can be performed routinely, providing a quick, simple, reproducible means of quantitating specific antibody concentrations, with sensitivity greater than 1 nanogram per milliliter. With this method, quantitation of IgG antibodies to any other viral antigen can be reliably and precisely determined. C1 W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. CHILDRENS HOSP LOS ANGELES,DEPT PEDIAT,LOS ANGELES,CA 90027. UNIV SO CALIF,SCH MED,DEPT MICROBIOL,LOS ANGELES,CA 90027. UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,LOS ANGELES,CA 90024. NR 27 TC 29 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT PY 1994 VL 54 IS 1-2 BP 99 EP 108 DI 10.1016/0165-5728(94)90236-4 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA PL703 UT WOS:A1994PL70300012 PM 7929807 ER PT J AU MCCUE, MP GUINAN, JJ AF MCCUE, MP GUINAN, JJ TI ACOUSTICALLY RESPONSIVE FIBERS IN THE VESTIBULAR NERVE OF THE CAT SO JOURNAL OF NEUROSCIENCE LA English DT Article DE SACCULE; OTOLITHS; AUDITORY SYSTEM; MAMMALIAN SOUND RECEPTION; MIDDLE-EAR MUSCLES; COCHLEAR NUCLEUS ID INNERVATING OTOLITH ORGANS; MIDDLE-EAR REFLEX; SQUIRREL-MONKEY; AUDITORY-NERVE; OLIVOCOCHLEAR NEURONS; BRAIN-STEM; ELECTRICAL-STIMULATION; STAPEDIUS MOTONEURONS; EVOKED-POTENTIALS; GUINEA-PIG AB Recordings were made from single afferent fibers in the inferior vestibular nerve, which innervates the saccule and posterior semicircular canal. A substantial portion of the fibers with irregular background activity increased their firing in response to moderately intense clicks and tones. In responsive fibers, acoustic clicks evoked action potentials with minimum latencies of less than or equal to 1.0 msec. Fibers fell into two classes, with the shortest latency either to condensation clicks (PUSH fibers) or to rarefaction clicks (PULL fibers). Low-frequency (800 Hz) tone bursts at moderately high sound levels (>80 dB SPL) caused synchronization of spikes to preferred phases of the tone cycle. PUSH and PULL fibers had preferred response phases approximately 180 degrees apart. These two response classes are consistent with fibers that innervate hair cells having opposite morphological polarizations, an arrangement found in the saccule. With low-frequency tone bursts, sound levels of greater than or equal to 90 dB SPL evoked increases in mean spike rate. Spike rates increased monotonically with sound level without saturating at levels less than or equal to 115 dB SPL. Contraction of the middle-ear muscles decreased responses to sound, consistent with the sound transmission path being through the middle ear. Several fibers were labeled with biocytin and traced. All labeled fibers had bipolar cell bodies in the inferior vestibular ganglion with peripheral processes extending toward the saccular nerve and central processes in the vestibular nerve. Two fibers were traced to the saccular epithelium. One fiber was traced centrally and arborized extensively in vestibular nuclei and a region ventromedial to the cochlear nucleus. Our results confirm and extend previous suggestions that the mammalian saccule responds to sound at frequencies and levels within the normal range of human hearing. We suggest a number of auditory roles that these fibers may play in the everyday life of mammals. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. FU NIDCD NIH HHS [R01 DC 00235, T32 DC 00006] NR 57 TC 199 Z9 207 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT PY 1994 VL 14 IS 10 BP 6058 EP 6070 PG 13 WC Neurosciences SC Neurosciences & Neurology GA PL028 UT WOS:A1994PL02800027 PM 7931562 ER PT J AU MCCUE, MP GUINAN, JJ AF MCCUE, MP GUINAN, JJ TI INFLUENCE OF EFFERENT STIMULATION ON ACOUSTICALLY RESPONSIVE VESTIBULAR AFFERENTS IN THE CAT SO JOURNAL OF NEUROSCIENCE LA English DT Article DE SACCULE; OTOLITHS; AUDITORY SYSTEM; MAMMALIAN SOUND RECEPTION; MIDDLE-EAR MUSCLES; COCHLEAR NUCLEUS ID PERIPHERAL INNERVATION PATTERNS; CROSSED-OLIVOCOCHLEAR-BUNDLE; AUDITORY-NERVE FIBERS; GENE-RELATED PEPTIDE; LATERAL LINE ORGAN; HAIR-CELLS; ELECTRICAL-STIMULATION; DISCHARGE PROPERTIES; SEMICIRCULAR CANALS; UTRICULAR MACULA AB In the preceding article (McCue and Guinan, 1994) we described a class of vestibular primary afferent fibers in the cat that responds vigorously to sounds at moderately high sound levels. Like their cochlear homologs, vestibular afferents and their associated hair cells receive efferent projections from brainstem neurons. In this report, we explore efferent influences on the background activity and tone burst responses of the acoustically responsive vestibular afferents. Shock-burst stimulation of efferents excited acoustically responsive vestibular afferents; no inhibition was seen. A fast excitatory component built up within 100-200 msec of shock-burst onset and decayed with a similar time course at the end of each shock burst. During repeated 400 msec shock bursts at 1.5 sec intervals, a slow excitatory component grew over 20-40 sec and then decayed, even though the shock bursts continued. Efferent stimulation excited acoustically responsive vestibular afferents without appreciably changing an afferent's sound threshold or its average sound-evoked response. This evidence supports the hypothesis that excitation is due to efferent synapses on afferent fibers rather than on hair cells. Efferent stimulation enhanced the within-cycle modulation of afferent discharges evoked by a tone; that is, it increased the ''AC gain.'' No appreciable change was noted in the degree of phase rocking to low-frequency tones as measured by the synchronization index. Little or no improvement in the bidirectionality (linearity) of transduction was seen. Vestibular afferent responses to tones normally had one peak per cycle; however, during efferent stimulation, two peaks per cycle were sometimes seen. We hypothesize that this is caused by two driving components acting at different sound phases with the components differentially affected by efferent activity. We discuss the relationship of our findings to efferent influences on acoustic responses in cochlear afferent fibers. The acoustically responsive vestibular afferents provide a mammalian model for studying purely excitatory efferent effects in a hair cell system. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. HARVARD UNIV,MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. MIT,DEPT ELECT ENGN & COMP SCI,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. FU NIDCD NIH HHS [R01 DC 00235, T32 DC 00006] NR 48 TC 47 Z9 50 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT PY 1994 VL 14 IS 10 BP 6071 EP 6083 PG 13 WC Neurosciences SC Neurosciences & Neurology GA PL028 UT WOS:A1994PL02800028 PM 7931563 ER PT J AU SHEPHERD, GMG COREY, DP AF SHEPHERD, GMG COREY, DP TI THE EXTENT OF ADAPTATION IN BULLFROG SACCULAR HAIR-CELLS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE SENSORY TRANSDUCTION; SENSORY ADAPTATION; MECHANICAL SENSITIVITY; HAIR CELL AUDITORY SYSTEM; VESTIBULAR SYSTEM; SACCULUS ID MECHANOELECTRICAL TRANSDUCTION; BUNDLE; STEREOCILIA; DISPLACEMENT; DEPENDENCE; MOVEMENT; CURRENTS; CHANNELS; EAR AB Positive deflection of the sensory hair bundle of a vertebrate hair cell opens transduction channels to depolarize the cell. In bullfrog saccular hair cells, there is a subsequent adaptation process, whereby the proportion or transduction channels that are open, and thus the receptor current, declines toward the resting value. This occurs because the sensitivity curve, relating open probability to bundle deflection, shifts along the deflection axis in response to bundle deflections, in a manner consistent with a relaxation of mechanical tension on transduction channels. In this study we determined the extent of adaptation, measured as the shift of the sensitivity curve following deflection of the hair bundle. The shift was determined both by comparison of the receptor current in the adapted state to the resting sensitivity curve, and by comparison of pre- and postadapted sensitivity curves. The adaptive shift approached steady state with a time constant of 20-30 msec, and was at steady state within 150 msec. For all positive and for small negative deflections, both methods showed a shift that was similar to 80% of the deflection. For larger negative deflections, the shift reached a fixed limit that was 100-500 nm negative to the freestanding bundle position. The limited extent of adaptation confers a time-dependent sensitivity: the cell has an instantaneous or phasic sensitivity curve that is steep, and steady-state or tonic sensitivity curve that is about five times broader. It also suggests the existence of two additional structural elements within the transduction apparatus. A revised quantitative theory accommodates these elements. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02114. HOWARD HUGHES MED INST,NEUROSCI GRP,BOSTON,MA 02114. RI Shepherd, Gordon/F-2679-2010; OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [DC00304] NR 31 TC 71 Z9 72 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT PY 1994 VL 14 IS 10 BP 6217 EP 6229 PG 13 WC Neurosciences SC Neurosciences & Neurology GA PL028 UT WOS:A1994PL02800041 PM 7931574 ER PT J AU TATTER, SB OGILVY, CS GOLDEN, JA OJEMANN, RG LOUIS, DN AF TATTER, SB OGILVY, CS GOLDEN, JA OJEMANN, RG LOUIS, DN TI 3RD VENTRICULAR XANTHOGRANULOMAS CLINICALLY AND RADIOLOGICALLY MIMICKING COLLOID CYSTS SO JOURNAL OF NEUROSURGERY LA English DT Note DE XANTHOGRANULOMA; 3RD VENTRICLE; CHOROID PLEXUS; MAGNETIC RESONANCE IMAGING; COLLOID CYST; DIFFERENTIAL DIAGNOSIS ID 3RD VENTRICLE; SYMPTOMATIC XANTHOGRANULOMA; CHOROID-PLEXUS; HYDROCEPHALUS; CT; ASPIRATION; MR AB Two cases are reported of third ventricle masses that were clinically and radiographically indistinguishable from pure colloid cysts. A 21- and a 36-year-old man presented with 5-year and 10-day histories of headache, respectively. Magnetic resonance (MR) imaging revealed smooth, homogeneous masses in the anterior third ventricle that were iso- to hyperintense on T-1-weighted MR images and hyperintense on T-2-weighted images. There was little enhancement with intravenous contrast material. In both patients, craniotomies were performed and histopathological examination revealed xanthogranulomas of the choroid plexus with only microscopic foci of colloid cyst-like structures. These cases illustrate that xanthogranulomas of the third ventricle may clinically and radiologically mimic pure colloid cysts, that a range of MR imaging signals can be seen, and that craniotomy rather than stereotactic aspiration is the indicated treatment. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 23 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1994 VL 81 IS 4 BP 605 EP 609 DI 10.3171/jns.1994.81.4.0605 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA PJ919 UT WOS:A1994PJ91900016 PM 7931596 ER PT J AU UCHIYAMA, M KANTOFF, PW KAPLAN, WD AF UCHIYAMA, M KANTOFF, PW KAPLAN, WD TI GALLIUM-67-CITRATE IMAGING IN EXTRAGONADAL AND GONADAL SEMINOMAS - RELATIONSHIP TO RADIOLOGIC FINDINGS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE GALLIUM-67-CITRATE IMAGING; CT SCAN; SEMINOMA; EXTRAGONADAL SEMINOMA ID COMPUTED-TOMOGRAPHY; GA-67 SCINTIGRAPHY; HODGKINS-DISEASE; CHEMOTHERAPY; LYMPHOMA; GA-67-CITRATE; MASSES; CT AB The results and analysis of baseline and follow-up Ga-67 imaging in three patients with extragonadal seminoma were compared to those of nine patients with primary and metastatic gonadal seminomas. Gallium-67 tumor avidity was scored (0-6) relative to accumulation in the sternum and the liver. Response time to systemic therapy for Ga-67 imaging compared to other radiological examinations was also measured. Results: Prior to therapy, Ga-67 scan sensitivity was 100%, (3/3) in patients with extragonadal seminomas and 90%, (9/10) for primary and radiologically evident metastatic sites in patients with gonadal seminomas. The combined sensitivity was 92%, (12/13) with the smallest Ga-67 scan detecting a mass 1.5 cm in diameter. There was no significant difference in Ga-67 avidity or sensitivity between extragonadal and gonadal sites. Following chemotherapy, CT scanning demonstrated residual radiologic abnormalities in all three extragonadal seminoma tumor sites and 5/8 metastatic gonadal seminoma tumor sites. However, the Ga-67 scan was normal in 10/11 sites at the first radionuclide examination after systemic therapy, indicating no active tumor, an observation supported by clinical follow-up from 6 to 72 mo. Conclusion: Gallium-67 scanning appears useful in the management of patients with both extragonadal and gonadal seminoma and may be useful in differentiating active disease from fibrosis in the treated patient with a post-therapy residual radiologic mass. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02115. NR 22 TC 8 Z9 8 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 1994 VL 35 IS 10 BP 1624 EP 1630 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PK362 UT WOS:A1994PK36200013 PM 7931660 ER PT J AU SHOUP, TM FISCHMAN, AJ JAYWOOK, S BABICH, JW STRAUSS, HW ELMALEH, DR AF SHOUP, TM FISCHMAN, AJ JAYWOOK, S BABICH, JW STRAUSS, HW ELMALEH, DR TI SYNTHESIS OF FLUORINE-18-LABELED BIOTIN DERIVATIVES - BIODISTRIBUTION AND INFECTION LOCALIZATION SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE INFECTION; PET; BIOTIN; RADIOFLUORINE ID AVIDIN; TUMOR; STREPTAVIDIN; ANTIBODIES; IGG AB Recently there has been much interest in the exploitation of the high binding affinity of avidin/biotin as a means of targeting drugs and radionuclides for in vivo applications. We are interested in broadening the application of the avidin/biotin complex to PET. To this end we set out to prepare F-18-labeled biotin analogs. Methods: Two F-18 biotin derivatives, [3aS-(3a alpha,4 beta,6a alpha)]-hexahydro-2-oxo-1H-thieno[3,4-d]imidazole-4-(N-3-(1-[F-18]fluoropropyl))pentanamide (1) and [3aS-(3a alpha,4 beta,6a alpha)]-tetrahydro-4-(5-(1-[F-18]fluoropentyl)-1H-thieno[3,4-d]imidazol-2(3H)-(2) were prepared with high specific activity (NCA) and evaluated for their potential in infection localization. Results: Compound 1 binds to avidin and the biodistribution of these derivatives were studied in Escherichia coli infected rats. Half of the infected rats were treated with avidin 24 hr prior to intravenous injection of the F-18-labeled biotin analogs. Biotin 1, without avidin pretreatment, showed a selectivity of 6.08 +/- 1.12 for infection compared to normal muscle. With avidin pretreatment, selectivity increased slightly, giving an infection to normal muscle ratio of 6.39 +/- 0.96. In contrast, the biodistribution of biotin 2 indicated more binding to normal muscle with an infection to normal muscle ratio of 0.58 +/- 0.07. This lack of selectivity illustrates the importance of the side-chain amide group in infection localization. There was some defluorination of 1 and 2, as evidenced by increased F-18 bone uptake after 60 min: 2.94 +/- 0.37 and 1.17 +/- 0.21 %IG/g +/- s.d., respectively. Conclusions: Biotin derivatives could be radiofluorinated with high specific activity. Biotin 1, is a potential positron tomography tracer for infection imaging. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NR 16 TC 37 Z9 37 U1 1 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 1994 VL 35 IS 10 BP 1685 EP 1690 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PK362 UT WOS:A1994PK36200025 PM 7931672 ER PT J AU HE, YP SANDERSON, IR WALKER, WA AF HE, YP SANDERSON, IR WALKER, WA TI UPTAKE, TRANSPORT AND METABOLISM OF EXOGENOUS NUCLEOSIDES IN INTESTINAL EPITHELIAL-CELL CULTURES SO JOURNAL OF NUTRITION LA English DT Article DE CACO-2 CELLS; IEC-6 CELLS; NUCLEOSIDES; UPTAKE; TRANSPORT ID ANIMAL-CELLS; URIDINE TRANSPORT; LINE CACO-2; DIFFERENTIATION; NITROBENZYLTHIOINOSINE; ERYTHROCYTES; NUCLEOTIDES; KINETICS; SYSTEM; MODEL AB The uptake and transport of nucleosides (adenosine, cytidine, guanosine, thymidine, uridine and inosine) were examined in intestinal cell lines (Caco-2 and IEC-6). Well-differentiated Caco-2 cells took up significantly more uridine and thymidine than less-differentiated cells over 24 h. These differences were reflected in the resulting trichloroacetic acid-soluble (nucleotide, nucleoside and nucleobase) pool sizes rather than in differences in nucleic acid incorporation. IEC-6 cells have smaller soluble pools than Caco-2 cells, and the uptake of nucleosides over 60 min reflected this difference. Caco-2 cells transported significantly more thymidine, cytidine, guanosine, adenosine and inosine into acid-soluble pools than IEC-6 cells. Caco-2 cells were grown on filters to examine the transcellular transport of nucleosides and to examine the chemical form in which nucleosides appeared at the basolateral aspect of the cell monolayer. The pattern of transport varied for individual nucleosides. The transport of cytidine and guanosine was significantly greater in the apical-to-basolateral direction than in the opposite direction over 2 h. No purine nucleoside was transported intact across the Caco-2 cell monolayer in either direction, with the majority of the transported material appearing as nucleobases. Nucleobases also represented the main metabolites of pyrimidines transported. However, some cytidine and uridine were detectable, but each constituted <20% of transported material. Nucleosides are therefore transported by enterocytes but metabolized during transport. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02129. FU NICHD NIH HHS [HD-31852, HD-12437]; NIDDK NIH HHS [DK-33506] NR 31 TC 39 Z9 41 U1 1 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD OCT PY 1994 VL 124 IS 10 BP 1942 EP 1949 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PM637 UT WOS:A1994PM63700007 PM 7931703 ER PT J AU RAPPAPORT, JM GULLIVER, JM PHILLIPS, DP VANDORPE, RA MAXNER, CE BHAN, V AF RAPPAPORT, JM GULLIVER, JM PHILLIPS, DP VANDORPE, RA MAXNER, CE BHAN, V TI AUDITORY TEMPORAL RESOLUTION IN MULTIPLE-SCLEROSIS SO JOURNAL OF OTOLARYNGOLOGY LA English DT Article AB Disturbances of hearing in multiple sclerosis patients have been variably reported, likely because standard audiologic testing emphasizes assessment of peripheral, rather than central, auditory function. This study investigated a group of patients with multiple sclerosis (MS), prospectively selected on the basis of magnetic resonance imaging (MRI) scans. Five of these patients had demyelinating lesions that included the rostral auditory fibre tracts, while another seven patients had lesions restricted to brainstem auditory sites. A further four had no lesions in the distribution of their auditory pathways. A comprehensive battery of audiometric tests, including standard audiometry and retrocochlear testing, was performed. In addition, their findings on electrophysiologic testing, including auditory brainstem responses (ABR) and middle latency responses (MLR), were studied. Finally, their performances in gap detection and speech recognition in continuous and interrupted background noise were examined to assess their auditory temporal resolution. The MS patients were found to be selectively impaired under the interrupted masker of this speech-in-noise paradigm, confirming a temporal processing defect. Furthermore, these patients' performances suggested a predominant role of forebrain pathways in mediating auditory temporal resolution. RP RAPPAPORT, JM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. RI Phillips, Dennis/A-6496-2011 NR 0 TC 26 Z9 29 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0381-6605 J9 J OTOLARYNGOL JI J. Otolaryngol. PD OCT PY 1994 VL 23 IS 5 BP 307 EP 324 PG 18 WC Otorhinolaryngology SC Otorhinolaryngology GA PK990 UT WOS:A1994PK99000001 PM 7807634 ER PT J AU KEATING, PA LINDBLOM, B LUBKER, J KREIMAN, J AF KEATING, PA LINDBLOM, B LUBKER, J KREIMAN, J TI VARIABILITY IN JAW HEIGHT FOR SEGMENTS IN ENGLISH AND SWEDISH VCVS SO JOURNAL OF PHONETICS LA English DT Article ID SPEECH; DYNAMICS AB This study compares the extent of coarticulatory influences of vowels on consonants and consonants on vowels in VCV utterances from English and Swedish speakers. Three vowels and ten consonants form the VCV utterances, with V1 = V2 and the nuclear stress on the second vowel. The measure of coarticulation is the vertical height of the jaw, which was determined using the Stockholm University Movetrack magnetometer system. Results of the experiment indicate that the two languages behave similarly overall, and that vowels are overall more open and overall more variable than are consonants. However, little of the variation in vowel height is attributable to consonant context, whereas much of the variation in consonant height is attributable to vowel context, and the effect of vowel context on consonant height is statistically reliable whereas the effect of consonant context on vowel height is not. These results support the proposal by Lindbolm (1983) that consonant segments may accommodate their jaw heights to those of neighboring vowels. The results also weakly support his proposal that consonants differ in their propensity to coarticulate, with alveolar consonants showing less effect of vowel context and /h/ the most. C1 UNIV STOCKHOLM,DEPT LINGUIST,STOCKHOLM,SWEDEN. UNIV VERMONT,COLL ARTS & SCI,BURLINGTON,VT 05405. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. RP KEATING, PA (reprint author), UNIV CALIF LOS ANGELES,DEPT LINGUIST,PHONET LAB,LOS ANGELES,CA 90024, USA. NR 26 TC 35 Z9 35 U1 0 U2 1 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0095-4470 J9 J PHONETICS JI J. Phon. PD OCT PY 1994 VL 22 IS 4 BP 407 EP 422 PG 16 WC Linguistics; Language & Linguistics SC Linguistics GA QB576 UT WOS:A1994QB57600004 ER PT J AU ZWEBEN, JE CLARK, HW AF ZWEBEN, JE CLARK, HW TI TRAUMATIC EXPERIENCES AND SUBSTANCE-ABUSE - INTRODUCTION SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article C1 UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA 94143. SAN FRANCISCO VET AFFAIRS MED CTR,DEPT PSYCHIAT,SUBSTANCE ABUSE SERV,SAN FRANCISCO,CA. RP ZWEBEN, JE (reprint author), FOURTEENTH ST CLIN & MED GRP & E BAY COMMUNITY RECOVERY PROJECT,OAKLAND,CA, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD OCT-DEC PY 1994 VL 26 IS 4 BP 323 EP 325 PG 3 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA PY835 UT WOS:A1994PY83500001 ER PT J AU ZWEBEN, JE CLARK, HW SMITH, DE AF ZWEBEN, JE CLARK, HW SMITH, DE TI TRAUMATIC EXPERIENCES AND SUBSTANCE-ABUSE - MAPPING THE TERRITORY SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE ADDICTION; RECOVERY-ORIENTED THERAPY; SUBSTANCE ABUSE; TRAUMATIC EXPERIENCES; POSTTRAUMATIC STRESS DISORDER ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; DISSOCIATIVE EXPERIENCES; GENERAL-POPULATION; PHYSICAL ABUSE; VICTIMIZATION; INPATIENTS; SYMPTOMS; RECOVERY AB This article examines the relationships between various types of traumatic experiences and addictive behavior, with an eye to formulating effective treatment strategies. Interventions in the posttraumatic stress disorder (PTSD) and related fields are reviewed in an effort to understand how best to integrate them into substance abuse treatment. The recovery-oriented therapy model is used as a framework to define treatment tasks at each stage of the recovery process: how one addresses painful issues depends on the objective, given the recovery stage at hand. These tasks include making a commitment to abstinence, stopping alcohol and other drug use, consolidating abstinence and changing lifestyles, and addressing short- and long-term psychosocial issues. The article focuses on the clinical features of PTSD in an effort to enhance the practitioner's ability to address this disorder within the context of substance abuse treatment. Finally, recommendations are offered for training practitioners at varying skill levels in the addiction treatment field. C1 FOURTEENTH ST CLIN & MED GRP & E BAY COMMUNITY RECOVERY PROJECT,OAKLAND,CA. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA 94143. HAIGHT ASHBURY FREE MED CLIN INC,SAN FRANCISCO,CA. MERRITH PERALTA INST,OAKLAND,CA. SAN FRANCISCO VET AFFAIRS MED CTR,DEPT PSYCHIAT,SUBSTANCE ABUSE SERV,SAN FRANCISCO,CA. NR 64 TC 53 Z9 54 U1 1 U2 7 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD OCT-DEC PY 1994 VL 26 IS 4 BP 327 EP 344 PG 18 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA PY835 UT WOS:A1994PY83500002 PM 7884595 ER PT J AU ROSAL, MC DOWNING, J LITTMAN, AB AHERN, DK AF ROSAL, MC DOWNING, J LITTMAN, AB AHERN, DK TI SEXUAL FUNCTIONING POSTMYOCARDIAL INFARCTION - EFFECTS OF BETA-BLOCKERS, PSYCHOLOGICAL STATUS AND SAFETY INFORMATION SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE SEXUAL BEHAVIOR; MYOCARDIAL INFARCTION; ADRENERGIC BETA RECEPTOR; BLOCKADERS; DEPRESSION; ANXIETY; PHYSICIAN-PATIENT COMMUNICATION ID ANTIHYPERTENSIVE AGENTS; HYPERTENSIVE PATIENTS; BYPASS-SURGERY; BLOCKING-DRUGS; DYSFUNCTION; THERAPY; ADJUSTMENT; VARIABLES; SYMPTOMS; BEHAVIOR AB Impaired sexual functioning limits the quality of life of 34-75% of post-myocardial infarction (MI) patients. This study examined the effects of three factors: (a) beta-blocker intake, (b) psychological distress, and (c) information about safety of sexual activity, on post-MI decreased sexual functioning. Sixty-three male post-MI, post-cardiac rehabilitation patients and their spouses participated in the study. Analyses of partial variance were conducted to test for the effect of each factor on sexual functioning. Controlling for age, results revealed that patients' psychological distress explained uniquely 24% of the variance on decreased post-MI sexual activity (p<0.002). Beta-blocker intake and message received with regard to sexual activity safety were not significant predictors of observed changes. Interdisciplinary assessments and interventions are recommended. C1 HARVARD UNIV, SCH MED,MASSACHUSETTS GEN HOSP,DEPT CARDIOL, PREVENT CARDIOL UNIT, CAMBRIDGE, MA 02138 USA. RP HARVARD UNIV, SCH MED, MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BEHAV MED UNIT, CAMBRIDGE, MA 02138 USA. NR 54 TC 7 Z9 7 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 EI 1879-1360 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD OCT PY 1994 VL 38 IS 7 BP 655 EP 667 DI 10.1016/0022-3999(94)90018-3 PG 13 WC Psychiatry SC Psychiatry GA PW599 UT WOS:A1994PW59900003 PM 7877120 ER PT J AU LYNCH, TJ PEAKE, WT ROSOWSKI, JJ AF LYNCH, TJ PEAKE, WT ROSOWSKI, JJ TI MEASUREMENTS OF THE ACOUSTIC INPUT IMPEDANCE OF CAT EARS - 10-HZ TO 20-KHZ SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Review ID TYMPANIC MEMBRANE VIBRATIONS; FINITE-ELEMENT MODEL; MIDDLE-EAR; STATIC PRESSURE; REFLECTION COEFFICIENT; FREQUENCY-RESPONSE; SOUND-PRESSURE; EARDRUM; TRANSMISSION; PROPAGATION AB The acoustic input impedance of the ear is a useful measure of the behavior of the middle ear and of its effect on the acoustics of the external ear. A high-impedance acoustic source with an integral microphone was designed for acoustic-impedance measurements. The source's Norton equivalent circuit was determined from measurements of the sound pressure it generated in known acoustic loads. Tests on simple acoustic configurations show errors in impedance measurements of less than 10% in magnitude and 7 degrees in angle over a frequency range from 10 Hz to 10 kHz with increasing errors at higher frequencies. Measurements at the tympanic membrane (TM) on five cat ears with widely opened middle-ear cavities show an impedance that is compliance-like below 0.3 kHz and approximately resistive above 2 kHz. With the cavities intact the impedance magnitude is somewhat larger for low frequencies, has a sharp maximum near 4 kHz, and at the highest frequencies is little affected by the state of the cavities. Impedance magnitude varies among ears by a factor of 3. The pressure reflection-coefficient that is determined from the impedance is frequency dependent with magnitude between 0.2 and 1. To characterize the motion transformation of the TM we calculate the ratio of tympanic-membrane volume velocity to the velocity of the mallear umbo, called here the kinematic area A(TK). This complex quantity is constant with an angle of zero for frequencies below 0.6 kHz, but at higher frequencies both magnitude and angle of A(TK) vary with frequency. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,BOSTON,MA 02114. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. FU NIDCD NIH HHS [5 RO1 DC00194, 8 PO1 DC00119]; NINDS NIH HHS [5 T32 NS07047] NR 104 TC 50 Z9 51 U1 1 U2 8 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 1994 VL 96 IS 4 BP 2184 EP 2209 DI 10.1121/1.410160 PG 26 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA PL708 UT WOS:A1994PL70800024 PM 7963032 ER PT J AU SPENCER, T BIEDERMAN, J WILENS, T AF SPENCER, T BIEDERMAN, J WILENS, T TI TRICYCLIC ANTIDEPRESSANT TREATMENT OF CHILDREN WITH ADHD AND TIC DISORDERS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; TOURETTES-SYNDROME; CLINICAL-RESPONSE; DESIPRAMINE; ADD C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SPENCER, T (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,FRUIT ST,BOSTON,MA 02114, USA. NR 17 TC 11 Z9 12 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 OCT PY 1994 VL 33 IS 8 BP 1203 EP 1204 DI 10.1097/00004583-199410000-00016 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA PH203 UT WOS:A1994PH20300018 PM 7982871 ER PT J AU DRAKE, LA FALLON, JD SOBER, A BRENEMAN, DL BROWN, RH CHALKER, D EDWARDS, L FUNICELLA, T GREENE, SL KANTOR, I KATZ, HI MAIZE, JC MILLIKAN, LE MONROE, EW RAIMER, SS SCHUPBACH, CW SMITH, EB AF DRAKE, LA FALLON, JD SOBER, A BRENEMAN, DL BROWN, RH CHALKER, D EDWARDS, L FUNICELLA, T GREENE, SL KANTOR, I KATZ, HI MAIZE, JC MILLIKAN, LE MONROE, EW RAIMER, SS SCHUPBACH, CW SMITH, EB TI RELIEF OF PRURITUS IN PATIENTS WITH ATOPIC-DERMATITIS AFTER TREATMENT WITH TOPICAL DOXEPIN CREAM SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ECZEMA AB Background: Atopic dermatitis is associated with severe pruritus for which effective topical treatment is lacking. As a potent H-1 and H-2 antagonist, the antipruritic effect of topical doxepin was first demonstrated in histamine-induced itch in nonatopic volunteers. Objective: The current study was undertaken to compare the efficacy and safety of topical 5% doxepin cream in relieving pruritus associated with atopic dermatitis. Methods: A total of 270 patients with atopic dermatitis who had daily moderate to severe pruritus for at least 1 week were enrolled in the double-blind, vehicle-controlled, multicenter study. Treatment was randomly assigned: 5% doxepin cream or vehicle cream was applied twice on the day of the baseline visit and four times daily for the remainder of the 7-day trial. Results: Relief of pruritus was achieved in 85% of doxepin-treated patients and 57%, of vehicle-treated patients by day 7; a majority of these positive responses occurred during the first 24 hours. Pruritus severity scores demonstrated significantly greater improvement with topical doxepin at each study visit (p < 0.01). Visual analogue scales for pruritus severity and pruritus relief showed similar improvement in the doxepin-treated group. At each of three visits, the physician's global evaluation for relief of pruritus also showed significant improve ment in the doxepin treatment group (p < 0.01). The physician's global evaluations of eczema significantly favored topical doxepin on day 7 (p < 0.01). Nineteen patients withdrew from the study because of adverse effects (doxepin, n = 16; vehicle, n = 3). The most commonly reported were localized stinging or burning (doxepin group, n = 39; vehicle group, n = 34) and drowsiness (doxepin group, n = 37; vehicle group, n = 3), all of which decreased in fre- quency and severity over time. Conclusion: Topical doxepin is effective in reducing pruritus in patients with atopic dermatitis. It has an apparent short-term low risk of major side effects or sensitization. C1 RACINE MED CLIN,RACINE,WI. RP DRAKE, LA (reprint author), MASSACHUSETTS GEN HOSP,DERMATOL CLIN INVEST UNIT,ROOM 505,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 101 Z9 101 U1 0 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 1994 VL 31 IS 4 BP 613 EP 616 PG 4 WC Dermatology SC Dermatology GA PJ914 UT WOS:A1994PJ91400011 PM 8089287 ER PT J AU HUTTER, AM AF HUTTER, AM TI CARDIOVASCULAR-ABNORMALITIES IN THE ATHLETE - ROLE OF THE PHYSICIAN SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material RP HUTTER, AM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV CARDIOL,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1994 VL 24 IS 4 BP 851 EP 853 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PN845 UT WOS:A1994PN84500002 PM 7930214 ER PT J AU MARON, BJ BROWN, RW MCGREW, CA MITTEN, MJ CAPLAN, AL HUTTER, AM AF MARON, BJ BROWN, RW MCGREW, CA MITTEN, MJ CAPLAN, AL HUTTER, AM TI ETHICAL, LEGAL AND PRACTICAL CONSIDERATIONS AFFECTING MEDICAL DECISION-MAKING IN COMPETITIVE ATHLETES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Discussion C1 AMER LEAGUE PROF BASEBALL CLUBS,NEW YORK,NY 10022. UNIV NEW MEXICO,MED CTR,DIV SPORTS MED,ALBUQUERQUE,NM 87131. S TEXAS COLL LAW,HOUSTON,TX 77002. UNIV PENN,SCH MED,CTR BIOETH,PHILADELPHIA,PA 19104. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV CARDIOL,BOSTON,MA 02114. RP MARON, BJ (reprint author), MINNEAPOLIS HEART INST FDN,920 E 28TH ST,MINNEAPOLIS,MN 55407, USA. NR 0 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1994 VL 24 IS 4 BP 854 EP 860 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PN845 UT WOS:A1994PN84500003 PM 7930215 ER PT J AU SEMIGRAN, MJ COCKRILL, BA KACMAREK, R THOMPSON, BT ZAPOL, WM DEC, GW FIFER, MA AF SEMIGRAN, MJ COCKRILL, BA KACMAREK, R THOMPSON, BT ZAPOL, WM DEC, GW FIFER, MA TI HEMODYNAMIC-EFFECTS OF INHALED NITRIC-OXIDE IN HEART-FAILURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID PULMONARY-HYPERTENSION; CARDIAC TRANSPLANTATION; ORGANIC NITRATES; NITROPRUSSIDE; RELAXATION; PRESSURE; DISEASE; RISK AB Objectives. This study was performed to assess the utility of inhaled nitric oxide as a selective pulmonary vasodilator in patients with severe chronic heart failure and to compare its hemodynamic effects with those of nitroprusside, a nonselective vasodilator. Background. Preoperative pulmonary vascular resistance is a predictor of right heart failure after heart transplantation. Nonselective vasodilators administered preoperatively to assess the reversibility of pulmonary vasoconstriction cause systemic hypotension, limiting their utility. Methods. Systemic and pulmonary hemodynamic measure ments were made at baseline, during oxygen inhalation and with the addition of graded doses of inhaled nitric oxide or intravenous nitroprusside in 16 patients with New York Heart Association class III or IV heart failure referred for heart transplantation, Results. Pulmonary vascular resistance decreased to a greater extent with 80 ppm nitric oxide (mean +/- SEM 256 +/- 41 to 139 +/-14 dynes.s.cm(-5)) than with the maximally tolerated dose of nitroprusside (264 +/- 49 to 169 +/- 30 dynes.s.cm(-5), p < 0.05, nitric oxide vs. nitroprusside). Pulmonary capillary wedge pressure increased with 80 ppm nitric oxide (26 +/- 2 to 32 +/- 2 mm Hg, p < 0.05). Mean arterial pressure did not change with nitric oxide but decreased with nitroprusside. Seven of the 16 patients, including 1 patient who did not have an adequate decrease in pulmonary vascular resistance with nitroprusside but did with nitric oxide, have undergone successful heart transplantation. Conclusions. Inhaled nitric oxide is a selective pulmonary vasodilator in patients with pulmonary hypertension due to left heart failure and may identify patients with reversible pulmonary vasoconstriction in whom agents such as nitroprusside cause systemic hypotension. Inhaled nitric oxide causes an increase in left ventricular filling pressure by an unknown mechanism. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,PULM UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RESP THERAPY,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NHLBI NIH HHS [HL43297] NR 34 TC 124 Z9 126 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1994 VL 24 IS 4 BP 982 EP 988 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PN845 UT WOS:A1994PN84500023 PM 7930234 ER PT J AU MERINO, A COHEN, M BADIMON, JJ FUSTER, V BADIMON, L AF MERINO, A COHEN, M BADIMON, JJ FUSTER, V BADIMON, L TI SYNERGISTIC ACTION OF SEVERE WALL INJURY AND SHEAR FORCES ON THROMBUS FORMATION IN ARTERIAL-STENOSIS - DEFINITION OF A THROMBOTIC SHEAR RATE THRESHOLD SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PLATELET DEPOSITION; CORONARY-ARTERIES; BLOOD-FLOW; PLAQUE RUPTURE; VESSEL WALL; ANGIOPLASTY; DISEASE; SUBENDOTHELIUM; AGGREGATION AB Objectives. This study attempted to determine the influence of progressive deg Background. The severity of wall injury and increased shear forces have been proposed as the determinants of thrombus formation and growth in arterial stenosis. Methods. Carotid angioplasty was performed in 15 mongrel dogs to produce severe wall damage. Group I (n = 9) had arteries with damage only. In group II (n = 14), progressive degrees of stenosis mere produced at the center of the dilated area. Acute thrombus formation was evaluated by angiography at the time of angioplasty and platelet deposition/cm(2) quantified by indium-111 labeling 1 h after the procedure. Results. Severe wall damage (group I) produced a significant increase in platelet deposition compared with control arterial segments (8.19 +/- 3.82 vs. 3.62 +/- 2.52 platelets x 10(6)/cm(2) [mean +/- SD], p < 0.05), and the presence of a stenosis (group II) further increased platelet deposition (36.98 +/- 3.82 platelets x 10(6)/cm(2), p < 0.05). Angiographic filling defects or total occlusion was found in seven of the arteries in group II but in none in group I (p < 0.05). A shear rate of similar to 5,000 s(-1), corresponding to a critical stenosis of 70% and a 1.5- to 1.6-mm diameter, was found to identify the arteries in which thrombosis was likely to occur (p < 0.05). Four of 5 arteries <1.5 to 1.6 mm in diameter had angiographic filling defects or occlusion compared with 1 of 13 with less severe stenosis (p < 0.01). Conclusions. In low shear rate conditions, deep arterial injury will lead to mural thrombosis without further thrombus growth. When deep arterial injury occurs under critical local shear conditions, platelet deposition will be enhanced, and thrombosis may progress to total occlusion. C1 POLICLIN MIRAMAR, PALMA DE MALLORCA, SPAIN. HAHNEMANN UNIV, LIKOFF CARDIOVASC INST, PHILADELPHIA, PA 19102 USA. MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BOSTON, MA 02114 USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. CSIC, CARDIOVASC RES CTR, BARCELONA, SPAIN. RI BADIMON, LINA/O-4711-2014; Fuster, Valentin/H-4319-2015 OI BADIMON, LINA/0000-0002-9162-2459; Fuster, Valentin/0000-0002-9043-9986 FU NHLBI NIH HHS [HL-38933, HL-39840] NR 40 TC 40 Z9 41 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1994 VL 24 IS 4 BP 1091 EP 1097 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PN845 UT WOS:A1994PN84500039 PM 7930203 ER PT J AU TAVARES, M DEPAOLA, PF SOPARKAR, P AF TAVARES, M DEPAOLA, PF SOPARKAR, P TI USING A FLUORIDE-RELEASING RESIN TO REDUCE CERVICAL SENSITIVITY SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID DENTIN HYPERSENSITIVITY; TEETH; PAIN AB Significant research indicates that dental hypersensitivity is caused by open dentinal tubules. A review of such research is presented as well as results of a study using fluoride resin in a composite restoration to reduce sensitivity. C1 FORSYTH DENT CTR,DEPT CLIN TRIALS,BOSTON,MA 02115. FU NIDCR NIH HHS [DE-07009] NR 24 TC 13 Z9 14 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1994 VL 125 IS 10 BP 1337 EP 1342 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PY411 UT WOS:A1994PY41100013 PM 7844298 ER PT J AU GERETY, MB WILLIAMS, JW MULROW, CD CORNELL, JE KADRI, AA ROSENBERG, J CHIODO, LK LONG, M AF GERETY, MB WILLIAMS, JW MULROW, CD CORNELL, JE KADRI, AA ROSENBERG, J CHIODO, LK LONG, M TI PERFORMANCE OF CASE-FINDING TOOLS FOR DEPRESSION IN THE NURSING-HOME - INFLUENCE OF CLINICAL AND FUNCTIONAL-CHARACTERISTICS AND SELECTION OF OPTIMAL THRESHOLD SCORES SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID RESEARCH DIAGNOSTIC-CRITERIA; MAJOR DEPRESSION; MEDICAL OUTCOMES; ALZHEIMER TYPE; SCALE; DEMENTIA; COMMUNITY; CARE; MORTALITY; INVENTORY AB OBJECTIVE: To compare case-finding tools for depression in the nursing home setting and to evaluate effects of subject function, cognition, and disease number on test performance. DESIGN: Cross-sectional survey. SETTING: One academic and four community homes. SUBJECTS: One hundred thirty-four randomly selected, mildly cognitively impaired, functionally dependent residents. METHODS AND MEASURES: The Geriatric Depression Scale (GDS), Short Geriatric Depression Scale (SGDS), Center for Epidemiologic Studies Depression Scale (CES-D), and Brief Carrol Depression Rating Scale (BCDRS) were administered. The Structured Clinical Interview for DSM-III-R diagnoses was administered independently,. Operating characteristics and the effects of subject characteristics on test performance were evaluated using McNemar's test and logistic regression. Selection of ''optimal'' threshold scores was guided by Kraemer's quality indices and clinical judgment. RESULTS: Thirty-five subjects (26%) had major depression. No differences were found among the instruments in sensitivity (range 0.74-0.89), specificity (range 0.62-0.77), or area under the receiver operating curve (ROC) (range 0.85-0.91). Resident characteristics did not affect test performance. Quality indices showed the GDS and BCDRS met criteria for moderate to substantial agreement with the criterion standard, whereas the SGDS and the CES-D achieved only fair agreement. No change in threshold scores was warranted. CONCLUSIONS: The GDS and BCDRS performed well in the nursing home. As the GDS can serve as a both a case-finding and severity instrument, it is preferred. Use of brief, interviewer-administered tools may improve detection of depression in the nursing home. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. RP GERETY, MB (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 FU AHRQ HHS [1-U01-HS07397-02]; NIA NIH HHS [NIA UO1AG09117] NR 48 TC 120 Z9 121 U1 1 U2 4 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 1994 VL 42 IS 10 BP 1103 EP 1109 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PK179 UT WOS:A1994PK17900012 PM 7930337 ER PT J AU GERETY, MB AF GERETY, MB TI ADVERSE EVENTS - RELATED TO DRUGS OR IATROGENIC - REPLY SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. RP GERETY, MB (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 1994 VL 42 IS 10 BP 1132 EP 1133 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA PK179 UT WOS:A1994PK17900020 ER PT J AU SAGIE, A SCHWAMMENTHAL, E PALACIOS, IF KING, ME LEAVITT, M FREITAS, N WEYMAN, AE LEVINE, RA AF SAGIE, A SCHWAMMENTHAL, E PALACIOS, IF KING, ME LEAVITT, M FREITAS, N WEYMAN, AE LEVINE, RA TI SIGNIFICANT TRICUSPID REGURGITATION DOES NOT RESOLVE AFTER PERCUTANEOUS BALLOON MITRAL VALVOTOMY SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID PULMONARY VASCULAR-RESISTANCE; VALVE REPLACEMENT; VALVULOPLASTY; STENOSIS; ANNULOPLASTY; HYPERTENSION; TIME; ECHOCARDIOGRAPHY; QUANTIFICATION; MECHANISM AB A total of 318 consecutive patients with mitral stenosis underwent percutaneous mitral valvotomy at our institution from 1987 to 1993. Of those, 98 patients had color Doppler echocardiographic studies performed before, 24 hours after, and late after the intervention. On the basis of color Doppler echocardiographic grading of tricuspid regurgitation, 32 patients (32%; mean age 57 +/- 15 years) had significant (moderate or severe) tricuspid regurgitation before the intervention and were the subject of this study. The follow-up study was performed 18.4 +/- 13 months after the procedure, Successful percutaneous mitral valvotomy (greater than or equal to 1.5 cm(2) valve area or greater than or equal to 50% increase after valvotomy) with no restenosis at follow-up was achieved in 20 patients. Tricuspid regurgitation decreased by one grade (from severe to moderate) in only four subjects in this group and in none of the 12 patients who did not meet the criteria for successful percutaneous mitral valvotomy or who had restenosis. Thus tricuspid regurgitation did not improve in 88% of all patients studied. On average, no significant change was observed in the ratio of maximal tricuspid;regurgitant jet area to right atrial area 24 hours after percutaneous mitral valvotomy and at late follow-up (37% vs 33% vs 34%, respectively) or in any of the right heart dimensions, even in patients who underwent successful percutaneous mitral valvotomy. Right ventricular systolic pressure also did not change significantly on average in those patients (46 +/- 15 versus 42 +/- 14 versus 48 +/- 18 mm Hg, respectively). However, right ventricular dimensions did not decrease and tricuspid regurgitation did not resolve even in a subgroup of patients in whom right ventricular systolic pressure fell by more than 10 mm Hg (up to 41 mm Hg). C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC CATHETERIZAT LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP SAGIE, A (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,CARDIAC UNIT,VINCENT BURNHAM 5,BOSTON,MA 02114, USA. NR 36 TC 31 Z9 36 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD OCT PY 1994 VL 108 IS 4 BP 727 EP 735 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA PK514 UT WOS:A1994PK51400019 PM 7934109 ER PT J AU HORNBERGER, LK BENACERRAF, BR BROMLEY, BS SPEVAK, PJ SANDERS, SP AF HORNBERGER, LK BENACERRAF, BR BROMLEY, BS SPEVAK, PJ SANDERS, SP TI PRENATAL DETECTION OF SEVERE RIGHT-VENTRICULAR OUTFLOW TRACT OBSTRUCTION - PULMONARY STENOSIS AND PULMONARY ATRESIA SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID CONGENITAL HEART-DISEASE; FETAL ECHOCARDIOGRAPHY; DIAGNOSIS; FETUS; MANAGEMENT; ACCURACY; SPECTRUM; LIFE AB We reviewed the prenatal echocardiograms and clinical outcomes of 12 fetuses with severe valvar pulmonary stenosis (six cases) or pulmonary atresia (six cases), to identify in utero echocardiographic features associated with severe right ventricular outflow tract obstruction. The mean age at initial prenatal study was 25 +/- 6 weeks of gestation. The echocardiographic appearance of the four chamber view, the right ventricular outflow tract, and the pulmonary arteries were similar for severe pulmonary stenosis and pulmonary atresia. The four chamber view was abnormal in all 12 cases. Right atrial dilation, with or without tricuspid regurgitation, was a common feature of severe pulmonary stenosis (six patients) and pulmonary atresia (four patients). In two fetuses with pulmonary atresia and significant right ventricular hypoplasia, a large atrial septal defect and no obvious right atrial enlargement were seen. Right ventricular hypoplasia was a feature in five fetuses with pulmonary atresia and in five fetuses with a patent pulmonic valve. All six fetuses with severe pulmonary stenosis and four fetuses with pulmonary atresia had right ventricular hypertrophy. Tricuspid regurgitation was present in five fetuses with severe pulmonary stenosis and in two with pulmonary atresia. All of the fetuses with pulmonary atresia had retrograde blood flow in the ductus arteriosus by color flow mapping. Despite the presence of a patent pulmonary valve, three fetuses with severe pulmonary stenosis had no antegrade blood flow detected through the right ventricular outflow tract, and only retrograde ductal and pulmonary artery flow could be demonstrated. Ratios of the dimensions of right to left heart structures, including ventricular diameters and lengths, and diameters of the atrioventricular valve and great artery, were not statistically different between the fetuses with atresia and stenosis. Recognition of the echocardiographic features associated with severe right ventricular outflow tract obstruction, particularly abnormalities of the four chamber view, should facilitate detection of severe pulmonary stenosis and pulmonary atresia on routine fetal screening. However, differentiation between these two conditions antenatally in the absence of antegrade right ventricular outflow appears to be unreliable at present. C1 BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP HORNBERGER, LK (reprint author), CHILDRENS HOSP,DEPT CARDIOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Sanders, Stephen/0000-0003-3521-4044 NR 26 TC 23 Z9 26 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 1994 VL 13 IS 10 BP 743 EP 750 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA PL205 UT WOS:A1994PL20500003 PM 7823335 ER PT J AU RAZA, S KLAPHOLZ, H BENACERRAF, BR AF RAZA, S KLAPHOLZ, H BENACERRAF, BR TI TARLOV CYSTS - A CAUSE OF COMPLEX BILATERAL ADNEXAL MASSES ON PELVIC SONOGRAPHY SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Note C1 BETH ISRAEL HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA. RP RAZA, S (reprint author), BETH ISRAEL HOSP,DEPT RADIOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 9 TC 5 Z9 5 U1 0 U2 1 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 1994 VL 13 IS 10 BP 803 EP 805 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA PL205 UT WOS:A1994PL20500012 PM 7823343 ER PT J AU DRETLER, SP AF DRETLER, SP TI STONES SO JOURNAL OF UROLOGY LA English DT Editorial Material ID SHOCK-WAVE LITHOTRIPSY; EXTRACORPOREAL RP DRETLER, SP (reprint author), MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,BOSTON,MA 02114, USA. NR 9 TC 0 Z9 0 U1 0 U2 1 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 1994 VL 152 IS 4 BP 1099 EP 1100 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PF219 UT WOS:A1994PF21900012 PM 8072072 ER PT J AU GERBER, GS BISSADA, NK HULBERT, JC KAVOUSSI, LR MOORE, RG KANTOFF, PW RUKSTALIS, DB AF GERBER, GS BISSADA, NK HULBERT, JC KAVOUSSI, LR MOORE, RG KANTOFF, PW RUKSTALIS, DB TI LAPAROSCOPIC RETROPERITONEAL LYMPHADENECTOMY - MULTIINSTITUTIONAL ANALYSIS SO JOURNAL OF UROLOGY LA English DT Article DE PERITONEOSCOPY; TESTICULAR NEOPLASMS; LYMPH NODE EXCISION ID GERM-CELL TUMORS; LYMPH-NODE DISSECTION; STAGE-1 TESTICULAR-CARCINOMA; TESTIS CANCER; SURVEILLANCE; COMPLICATIONS; ORCHIDECTOMY; MANAGEMENT; METASTASES; PROTOCOL AB Modified unilateral laparoscopic retroperitoneal lymph node dissection was attempted in 20 patients with nonseminomatous testicular cancer. The procedure was completed in 18 men at a median operative length of 6 hours. Median estimated blood loss was 250 cc and median number of lymph nodes removed was 14.5. Nodal disease spread was noted in 3 of 18 patients (17%). Most patients were hospitalized for 3 days or less and had returned to normal activity levels within 2 to 3 weeks. Antegrade ejaculation was preserved in all 20 patients. Significant complications occurred in 6 of 20 patients (30%), with bleeding being the most common adverse event encountered. In 2 patients an abdominal incision and completion of the procedure by open retroperitoneal lymph node dissection were required due to significant bleeding following injury to the gonadal vessels. With a median followup of 10 months (range 2 to 25), 2 men had pulmonary disease recurrence and none had abdominal recurrence. Laparoscopic retroperitoneal lymph node dissection can be completed successfully in patients with stage I testicular cancer and may be most appropriate in those with limited risk of metastatic disease spread. The morbidity may be largely attributed to a steep learning curve. The efficacy of laparoscopic retroperitoneal lymph node dissection compared with standard techniques and determination of its role in patients with testicular cancer will require longer followup in larger groups of patients. C1 MED UNIV S CAROLINA,DEPT UROL,CHARLESTON,SC. UNIV MINNESOTA,SCH MED,DEPT UROL,MINNEAPOLIS,MN 55455. JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD 21205. DANA FARBER CANC INST,BOSTON,MA. RP GERBER, GS (reprint author), UNIV CHICAGO,PRITZKER SCH MED,DEPT SURG,UROL SECT,CHICAGO,IL 60637, USA. NR 20 TC 47 Z9 48 U1 0 U2 1 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 1994 VL 152 IS 4 BP 1188 EP 1191 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA PF219 UT WOS:A1994PF21900041 PM 8072092 ER PT J AU WANG, WB BIKEL, I MARSILIO, E NEWSOME, D LIVINGSTON, DM AF WANG, WB BIKEL, I MARSILIO, E NEWSOME, D LIVINGSTON, DM TI TRANSREPRESSION OF RNA-POLYMERASE-II PROMOTERS BY THE SIMIAN-VIRUS-40 SMALL T-ANTIGEN SO JOURNAL OF VIROLOGY LA English DT Article ID SV40 SMALL-T; CELLULAR DNA-SYNTHESIS; ADENOVIRUS E1A GENE; SMALL TUMOR-ANTIGEN; PROTEIN PHOSPHATASE-2A; TRANSFORMING FUNCTION; MUTATIONAL ANALYSIS; TRANS-ACTIVATION; ANTISENSE RNA; GROWTH-FACTOR AB Simian virus 40 (SV40) small t antigen (t) can activate transcription from certain RNA polymerase II and III promoters (M. Loeken, I. Bikel, D. M. Livingston, and J. Brady, Cell 55:1171-1177, 1988). Here we report a new function of t, its ability to repress human c-fos promoter and AP-1 transcriptional activity in CV-1P cells. This function is the product of a discrete N-terminal domain of t, because the large T antigen (T)it-common polypeptide, which contains only the first 82 amino acids common to both T and t of SV40, was, like the intact protein, an active repressor. The data further suggest that the t- and T/t-common-mediated repression of c-fos expression was most likely manifest at the level of transcription. In keeping with the possibility that t affects the expression of the genomic c-fos promoter, it also led to repression of AP-1 formation. Thus, SV40 t is both an activator and a repressor of transcription. Its ability to inhibit c-fos expression should be considered in light of the natural history of SV40 in its natural host. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 62 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1994 VL 68 IS 10 BP 6180 EP 6187 PG 8 WC Virology SC Virology GA PG541 UT WOS:A1994PG54100005 PM 8083958 ER PT J AU DELWART, EL SHEPPARD, HW WALKER, BD GOUDSMIT, J MULLINS, JI AF DELWART, EL SHEPPARD, HW WALKER, BD GOUDSMIT, J MULLINS, JI TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EVOLUTION IN-VIVO TRACKED BY DNA HETERODUPLEX MOBILITY ASSAYS SO JOURNAL OF VIROLOGY LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; SINGLE BASE SUBSTITUTIONS; PRIMARY HIV-1 INFECTION; ENVELOPE GENE; REVERSE-TRANSCRIPTASE; BIOLOGICAL PHENOTYPE; SEQUENCE VARIATION; VARIABLE DOMAIN; CHAIN-REACTION; AIDS AB High mutation rates and strong selective pressures imposed on human immunodeficiency viruses in vivo result in the formation of pools of genetic variants known as quasispecies. DNA heteroduplex mobility and tracking analyses were used to monitor the generation of HIV sequence diversity, to estimate quasispecies complexity, and to assess the turnover of genetic variants to approach an understanding of the relationship between viral quasispecies evolution in vivo and disease progression. Proviral DNA pools were nearly homogeneous soon after sexual transmission. The emergence and clearance of individual variants then occurred at different rates in different individuals. High quasispecies complexity was found in long-term-infected, asymptomatic individuals, while rapid CD4(+) cell decline and AIDS were often, but not always, associated,vith lower quasispecies complexity. Proviral genetic variation was often low following in vitro culture, because of the outgrowth of one or a few variants that often became more abundant only later as proviruses in peripheral blood mononuclear cells. These studies provide insight into the dynamics of human immunodeficiency virus sequence changes in vivo and illustrate the utility of heteroduplex analysis for the study of phenomena associated with rapid genetic changes. C1 STANFORD UNIV,SCH MED,DEPT IMMUNOL & MICROBIOL,STANFORD,CA 94305. CALIF DEPT HLTH SERV,VIRAL & RICKETTSIAL DIS LAB,BERKELEY,CA 94704. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. UNIV AMSTERDAM,ACAD MED CTR,HUMAN RETROVIRUS LAB,1105 AZ AMSTERDAM,NETHERLANDS. OI Delwart, Eric/0000-0002-6296-4484 FU NIAID NIH HHS [AI07328, N01 AI82515, R01 AI32885] NR 80 TC 272 Z9 280 U1 0 U2 2 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 1994 VL 68 IS 10 BP 6672 EP 6683 PG 12 WC Virology SC Virology GA PG541 UT WOS:A1994PG54100056 PM 8084001 ER PT J AU KREISBERG, JI GARONI, JA RADNIK, R AYO, SH AF KREISBERG, JI GARONI, JA RADNIK, R AYO, SH TI HIGH GLUCOSE AND TGF-BETA(1), STIMULATE FIBRONECTIN GENE-EXPRESSION THROUGH A CAMP RESPONSE ELEMENT SO KIDNEY INTERNATIONAL LA English DT Article ID GROWTH-FACTOR-BETA; SIGNAL TRANSDUCTION PATHWAYS; MESANGIAL CELLS; TRANSCRIPTIONAL ACTIVATION; CYCLIC-AMP; INDUCED BINDING; PROTEINS; FAMILY; PHOSPHORYLATION; INCREASE AB Previously, we reported that mesangial cells increased fibronectin, laminin and type IV collagen synthesis when cultured in the presence of high glucose (30 mM). Although mRNA levels for all three extracellular matrix (ECM) proteins were also increased in high glucose conditions, the mechanism for this increase was not known. In order to determine whether increased transcription was involved in the observed increase in fibronectin mRNA levels mesangial cells were transfected with a construct containing the 5'-flanking region of the fibronectin (FN) gene [position +69 to -510 base pairs (bp)] fused to the coding region of the chloramphenicol acetyltransferase (CAT) gene [FN-CAT (-510)]. Cells were transiently and stably transfected with this construct. Under serum-free conditions, high glucose increased CAT activity only in the presence of TGF beta(1) (referred to as TGF beta). The experiments were performed without serum because FN-CAT (-510) contains a serum responsive element. The increase in CAT was approximately twofold in transiently transfected cells and threefold in stably transfected cells. TGF beta alone increased CAT activity approximately 30%. Stimulation of fibronectin gene expression appeared to occur at the level of a cAMP response element (CRE) located -170 bp of the FN gene because cells transfected with a construct containing an oligonucleotide encoding for this CRE fused to a minimal fibronectin promoter (-56 bp) and a CAT reporter gene [CRE (-170) FN-CAT] displayed similar increments of CAT activity after treatment with high glucose and TGF beta. Gel shift mobility assays with a CRE oligonucleotide revealed multiple complexes with mesangial cell nuclear proteins. No differences in the mobility or abundance of complexes were observed in the different conditions tested. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP KREISBERG, JI (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDDK NIH HHS [DK 29787] NR 37 TC 48 Z9 49 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1994 VL 46 IS 4 BP 1019 EP 1024 DI 10.1038/ki.1994.362 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA PH786 UT WOS:A1994PH78600009 PM 7861696 ER PT J AU GOODMAN, WG RAMIREZ, JA BELIN, TR CHON, Y GALES, B SEGRE, GV SALUSKY, IB AF GOODMAN, WG RAMIREZ, JA BELIN, TR CHON, Y GALES, B SEGRE, GV SALUSKY, IB TI DEVELOPMENT OF ADYNAMIC BONE IN PATIENTS WITH SECONDARY HYPERPARATHYROIDISM AFTER INTERMITTENT CALCITRIOL THERAPY SO KIDNEY INTERNATIONAL LA English DT Article ID AMBULATORY PERITONEAL-DIALYSIS; COLLAGEN-SYNTHESIS; UREMIC PATIENTS; RENAL-FAILURE; RAT CALVARIAE; ALUMINUM; DISEASE; 1,25-DIHYDROXYVITAMIN-D3; OSTEODYSTROPHY; HYPERCALCEMIA AB Intermittent calcitriol therapy is commonly used to treat secondary hyperparathyroidism in patients undergoing regular dialysis, but there is little available information about the histologic response of bone to this form of therapy. Accordingly, 14 children and adolescents with biopsy-proven secondary hyperparathyroidism were treated with intermittent oral or intraperitoneal doses of calcitriol for 12 months. Biochemical indices of mineral metabolism including serum intact PTH levels were measured monthly throughout the study, and bone biopsies were repeated at the end of treatment. Before treatment, 11 patients had osteitis fibrosa and three had mild lesions of secondary hyperparathyroidism. Histologic improvement was seen in 12 of 14 patients, and osteitis fibrosa resolved in 10 of 11 cases. Bone formation decreased in all patients during intermittent calcitriol therapy, falling from 861 +/- 380 to 150 +/- 170 mu m(2)/mm(2)/day, P < 0.001. Bone formation decreased to normal in six patients, but six patients developed adynamic lesions of bone with subnormal bone formation rates. Serum PTH and alkaline phosphatase levels declined in those who developed adynamic bone, but values remained elevated in patients with normal rates of bone formation at follow-up evaluation. Neither the mean dose of calcitriol nor the average dose per kilogram body weight differed in patients with adynamic lesions. Thus, adynamic renal osteodystrophy develops in a substantial number of patients during intermittent calcitriol therapy. Although declining serum PTH and alkaline phosphatase levels suggest the development of the adynamic lesion, bone formation decreases in some patients despite persistently high serum PTH levels. Calcitriol may directly suppress osteoblastic activity in patients with secondary hyperparathyroidism when given in large doses to patients undergoing peritoneal dialysis. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOSTAT,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. FU NCRR NIH HHS [RR-00865]; NIAMS NIH HHS [AR-41853]; NIDDK NIH HHS [DK-35423] NR 35 TC 242 Z9 252 U1 0 U2 4 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1994 VL 46 IS 4 BP 1160 EP 1166 DI 10.1038/ki.1994.380 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA PH786 UT WOS:A1994PH78600027 PM 7861712 ER PT J AU SHIVDASANI, RA ANDERSON, KC AF SHIVDASANI, RA ANDERSON, KC TI HLA HOMOZYGOSITY AND SHARED HLA HAPLOTYPES IN THE DEVELOPMENT OF TRANSFUSION-ASSOCIATED GRAFT-VERSUS-HOST DISEASE SO LEUKEMIA & LYMPHOMA LA English DT Review DE HLA HOMOZYGOSITY; SHARED HLA HAPLOTYPES; TRANSFUSION-ASSOCIATED GRAFT VERSUS HOST DISEASE AB We review the pathogenesis, epidemiology and patient cases of transfusion-associated graft-versus-host disease (TA-GVHD) in the context of host inability to eliminate viable donor T-lymphocytes, This review is based on the published English-language literature pertaining to TA-GVHD, including case reports with HLA data on transfusion recipients as well as blood donors. The role of shared histocompatibility antigens between the donor and the recipient in promoting TA-GVHD is discussed critically. Since TA-GVHD is usually a fatal disease for which effective therapy is lacking, prevention is of utmost importance and guidelines for gamma-irradiation of cellular blood products are presented. TA-GVHD has been described in immunodeficient as well as in immunocompetent hosts, and following blood product transfusions from related as well as from unrelated donors. This review includes analysis of patient data in each of these settings and probability estimates based on principles of population genetics. We emphasize that transfusion of blood products from individuals who are homozygous at the HLA loci to heterozygous recipients who share that HLA haplotype occurs at a frequency proportional to the genetic homogeneity of the population and that the process mediating TA-GVHD in such instances appears to be independent of the host's immune status. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. NR 0 TC 10 Z9 10 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD OCT PY 1994 VL 15 IS 3-4 BP 227 EP 234 DI 10.3109/10428199409049718 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA PN901 UT WOS:A1994PN90100004 PM 7866271 ER PT J AU STONE, RM BERNSTEIN, SH DEMETRI, G FACKLAM, DP ARTHUR, K ANDERSEN, J ASTER, JC KUFE, D AF STONE, RM BERNSTEIN, SH DEMETRI, G FACKLAM, DP ARTHUR, K ANDERSEN, J ASTER, JC KUFE, D TI THERAPY WITH RECOMBINANT-HUMAN-ERYTHROPOIETIN IN PATIENTS WITH MYELODYSPLASTIC SYNDROMES SO LEUKEMIA RESEARCH LA English DT Article DE ERYTHROPOIETIN; MYELODYSPLASTIC SYNDROMES; HEMATOPOIETIC GROWTH FACTORS; COLONY STIMULATING FACTORS; BONE MARROW FAILURE; ANEMIA ID COLONY-STIMULATING FACTOR; CLINICAL-TRIAL; CIRCULATING ERYTHROPOIETIN; HUMAN INTERLEUKIN-3; ANEMIA; MARROW; DISORDERS; LEUKEMIA; CELLS AB We conducted a Phase I-II trial of recombinant human erythropoietin-beta (rhEPO) in patients with myelodysplastic syndrome (MDS). Patients with anemia and pathologically confirmed MDS were eligible for the study. Treatment consisted of rhEPO by subcutaneous injection thrice weekly for 6 weeks at one of three dose levels (100 U/kg (three patients), 200 U/kg (three patients) and 400 U/kg (14 patients)). Ferrous sulfate (325 mg po tid) was also administered if the transferrin saturation was below 30% (two patients). Patients were monitored with weekly CBC, white cell differential, and reticulocyte counts. Bone marrow examinations were performed at the conclusion of the treatment period and after a 2 week wash-out period. Patients who responded to therapy were continued on rhEPO at the same dose for 6 additional months. Response criteria included: 50% reduction in transfusion requirements compared with the 6 week pre-study period; doubling of reticulocyte count that was maintained on two determinations at least 1 week apart; or an increase in hemoglobin by at least 1.2 gm/dl without transfusions. Pre-treatment factors potentially predictive of response were analyzed by univariate analysis and in a multivariate fashion by classification and regression trees. Seven of the twenty patients sustained an untransfused rise in serum hemoglobin greater than or equal to 1.2 gm/dl. Four of the sixteen patients (including three of seven patients experiencing a rise in serum hemoglobin) who were transfusion-dependent prior to the study achieved a reduction or elimination of their transfusion requirements. Five of thirteen patients who received rhEPO during the extension phase had a continued response. A low baseline erythropoietin level (<50 mU/ml) was the best predictor of hemoglobin response when controlling for other variables, rhEPO has a role in the treatment of certain patients with MDS, particularly in those whose endogenous serum erythropoietin levels are not markedly elevated. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP STONE, RM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. NR 36 TC 16 Z9 17 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 1994 VL 18 IS 10 BP 769 EP 776 DI 10.1016/0145-2126(94)90059-0 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA PM879 UT WOS:A1994PM87900008 PM 7934135 ER PT J AU ABSHER, JR SULTZER, DL MAHLER, ME FISHMAN, J AF ABSHER, JR SULTZER, DL MAHLER, ME FISHMAN, J TI P(C) ANALYSIS FACILITATES DEMENTIA DIAGNOSIS SO MEDICAL DECISION MAKING LA English DT Article DE DEMENTIA; MULTIINFARCT; ALZHEIMERS DISEASE; DIAGNOSTIC TESTS; ROC ANALYSIS ID MULTI-INFARCT DEMENTIA; ADRDA WORK GROUP; ALZHEIMERS-DISEASE; CLINICAL-DIAGNOSIS; DIFFERENTIATION; ACCURACY; SCALE; TESTS AB A modified receiver operating characteristic (ROC) analysis technique was applied to a sample of 161 consecutive volunteers seen in a dementia clinic. Clinical, imaging, neuropsychological, and laboratory evaluation guided experienced clinicians in clinical diagnosis, taken as the ''gold standard.'' Two symptom inventories, the Hachinski Ischemic Score and the Dementia of the Alzheimer's Type Inventory, were obtained by clinicians who were blind to final clinical diagnosis; scores on these inventories correlate with the likelihoods of multiinfarct dementia and Alzheimer's disease, respectively. A disjunctive sequential testing strategy was analyzed such that subthreshold scores on the first test identified patients for whom the second test was considered. Both tests were analyzed at all possible cutoff-point combinations and in both possible testing sequences. Diagnoses based on these tests were compared with the clinical ''gold standard'' diagnoses to determine the accuracy of the testing procedures. The best strategy correctly classified 154/161 (95.6%) of the dementia patients and required cutoff points (5 for the HIS and 10 for the Dementia of the Alzheimer's Type Inventory) that were lower than those usually recommended for either test used alone (i.e., 7 and 14, respectively). The Hachinski Ischemic Score-then Dementia of the Alzheimer's Type inventory testing sequence was superior to the reverse strategy. A sensitivity analysis (varying prevalences of Alzheimer's disease, multi-infarct dementia, and other dementias) revealed similar test Performances across a wide range of prevalences. These data suggest. that simple clinical tests that take approximately 30 minutes to administer can produce diagnostic classifications of dementia that are similar to those of clinicians experienced in dementia diagnosis. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,BEHAV NEUROSCI SECT,PSYCHIAT SERV,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,NEUROBEHAV PROGRAM,LOS ANGELES,CA. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. FU NIA NIH HHS [AG00172, AG00260]; NIMH NIH HHS [MH00910] NR 30 TC 2 Z9 2 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD OCT-DEC PY 1994 VL 14 IS 4 BP 393 EP 402 DI 10.1177/0272989X9401400410 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA PL433 UT WOS:A1994PL43300010 PM 7808214 ER PT J AU WEBER, GF AF WEBER, GF TI THE PATHOPHYSIOLOGY OF REACTIVE OXYGEN INTERMEDIATES IN THE CENTRAL-NERVOUS-SYSTEM SO MEDICAL HYPOTHESES LA English DT Article ID HALLERVORDEN-SPATZ DISEASE; KINKY-HAIR SYNDROME; MULTIPLE-SCLEROSIS; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; ALZHEIMERS-DISEASE; FREE-RADICALS; GLUTATHIONE-PEROXIDASE; ASCORBIC-ACID; WHITE MATTER AB Current evidence for the participation of free radicals in diseases of the central nervous system is reviewed. We conclude that the pathogenesis is based on a uniform mechanism: free radicals preferentially attack myelin, which contains easily peroxidizable phospholipids. The basal ganglia seem to be a brain area that is especially susceptible to radical damage which is possibly related to the synthesis of neurotransmitters. The clinical picture of the resulting cell death is dominated by convulsions and retardation in childhood and by psychomotoric disability and dementia in adulthood. C1 HARVARD UNIV,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,DEPT PATHOL,BOSTON,MA 02115. NR 80 TC 33 Z9 35 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD OCT PY 1994 VL 43 IS 4 BP 223 EP 230 DI 10.1016/0306-9877(94)90070-1 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PN055 UT WOS:A1994PN05500008 PM 7838005 ER PT J AU HUTTER, AM AF HUTTER, AM TI CARDIOVASCULAR-ABNORMALITIES IN THE ATHLETE - THE ROLE OF THE PHYSICIAN SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Editorial Material RP HUTTER, AM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV CARDIOL,15 PARKMAN ST,BOSTON,MA 02114, USA. 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD OCT PY 1994 VL 26 IS 10 SU S BP S227 EP S229 PG 3 WC Sport Sciences SC Sport Sciences GA PM548 UT WOS:A1994PM54800002 PM 7934743 ER PT J AU MARON, BJ BROWN, RW MCGREW, CA MITTEN, MJ CAPLAN, AL HUTTER, AM CHEITLIN, M THOMPSON, P STRONG, W LEVINE, B DOUGLAS, P GARSON, A WILLIAMS, R AF MARON, BJ BROWN, RW MCGREW, CA MITTEN, MJ CAPLAN, AL HUTTER, AM CHEITLIN, M THOMPSON, P STRONG, W LEVINE, B DOUGLAS, P GARSON, A WILLIAMS, R TI ETHICAL, LEGAL, AND PRACTICAL CONSIDERATIONS IMPACTING MEDICAL DECISION-MAKING IN COMPETITIVE ATHLETES SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Discussion C1 AMER LEAGUE PROFESS BASEBALL CLUBS,NEW YORK,NY 10022. UNIV NEW MEXICO,MED CTR,DIV SPORTS MED,ALBUQUERQUE,NM 87131. S TEXAS COLL LAW,HOUSTON,TX 77002. UNIV PENN,SCH MED,CTR BIOETH,PHILADELPHIA,PA 19104. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV CARDIOL,BOSTON,MA 02114. RP MARON, BJ (reprint author), MINNEAPOLIS HEART INST FDN,928 E 28TH ST,MINNEAPOLIS,MN 55407, USA. NR 0 TC 5 Z9 5 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD OCT PY 1994 VL 26 IS 10 SU S BP S230 EP S237 PG 8 WC Sport Sciences SC Sport Sciences GA PM548 UT WOS:A1994PM54800003 PM 7934744 ER PT J AU BARBER, DL DANDREA, AD AF BARBER, DL DANDREA, AD TI ERYTHROPOIETIN AND INTERLEUKIN-2 ACTIVATE DISTINCT JAK KINASE FAMILY MEMBERS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; RECEPTOR GAMMA-CHAIN; INFECTED ERYTHROID-CELLS; HUMAN IL-2 RECEPTOR; SIGNAL-TRANSDUCTION; BETA-CHAIN; INTERFERON-ALPHA/BETA; FUNCTIONAL COMPONENT; CYTOPLASMIC DOMAIN; RESPONSIVE CELLS AB The erythropoietin (EPO) receptor and the interleukin-2 (IL-2) receptor beta-chain subunit are members of the cytokine receptor superfamily. They have conserved primary amino acid sequences in their cytoplasmic domains and activate phosphorylation of common substrates, suggesting common biochemical signaling mechanisms. We have generated a cell line, CTLL-EPO-R, that contains functional cell surface receptors for both EPO and IL-2. CTLL-EPO-R cells demonstrated similar growth kinetics in EPO and IL-2. Stimulation with EPO resulted in the rapid, dose-dependent tyrosine phosphorylation of JAK2. In contrast, stimulation with IL-2 or the related cytokine IL-4 resulted in the rapid, dose-dependent tyrosine phosphorylation of JAK1 and an additional 116-kDa protein. This 116-kDa protein was itself immunoreactive with a polyclonal antiserum raised against JAK2 and appears to be a novel member of the JAK kinase family. Immune complex kinase assays confirmed that IL-2 and IL-4 activated JAK1 and EPO activated JAK2. These results demonstrate that multiple biochemical pathways are capable of conferring a mitogenic signal in CTLL-EPO-R cells and that the EPO and IL-2 receptors interact with distinct JAK kinase family members within the same cellular background. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [R01 DK 43889-01] NR 67 TC 42 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1994 VL 14 IS 10 BP 6506 EP 6514 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100010 PM 7935373 ER PT J AU NEUMAN, E FLEMINGTON, EK SELLERS, WR KAELIN, WG AF NEUMAN, E FLEMINGTON, EK SELLERS, WR KAELIN, WG TI TRANSCRIPTION OF THE E2F-1 GENE IS RENDERED CELL-CYCLE DEPENDENT BY E2F DNA-BINDING SITES WITHIN ITS PROMOTER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETINOBLASTOMA PROTEIN BINDS; COMPLEX-FORMATION; DIHYDROFOLATE-REDUCTASE; ADENOVIRUS-E1A PREVENTS; VIRAL ONCOPROTEINS; RB PROTEIN; PRODUCT; P107; EXPRESSION; TRANSACTIVATION AB The cell cycle-regulatory transcription factor E2F-1 is regulated by interactions with proteins such as the retinoblastoma gene product and by cell cycle-dependent alterations in E2F-1 mRNA abundance. To better understand this latter phenomenon, we have isolated the human E2F-1 promoter. The human E2F-1 promoter, fused to a luciferase cDNA, gave rise to cell cycle-dependent luciferase activity upon transfection into mammalian cells in a manner Which paralleled previously reported changes in E2F-1 mRNA abundance. The E2F-1 promoter contains four potential E2F-binding sites organized as two imperfect palindromes. Gel shift and transactivation studies suggested that these sites can bind to E2F in vitro and in vivo. Mutation of the two E2F palindromes abolished the cell cycle dependence of the E2F-1 promoter. Thus, E2F-1 appears to be regulated at the level of transcription, and this regulation is due, at least in part, to binding of one or more E2F family members to the E2F-1 promoter. C1 DANA FARBER CANC INST,DIV NEOPLAST DIS MECH,BOSTON,MA 02115. NR 68 TC 233 Z9 233 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 1994 VL 14 IS 10 BP 6607 EP 6615 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100020 PM 7935380 ER PT J AU YAMAUCHI, N KIESSLING, AA COOPER, GM AF YAMAUCHI, N KIESSLING, AA COOPER, GM TI THE RAS/RAF SIGNALING PATHWAY IS REQUIRED FOR PROGRESSION OF MOUSE EMBRYOS THROUGH THE 2-CELL STAGE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; NERVE GROWTH-FACTOR; HA-RAS MUTATION; NIH 3T3 CELLS; MAP KINASE; FACTOR RECEPTOR; ETHYLENEDIAMINETETRAACETIC ACID; COMPLEX-FORMATION; MAJOR PRODUCTS; 2-CELL EMBRYO AB We have used microinjection of antisense oligonucleotides, monoclonal antibody, and the dominant negative Ras N-17 mutant to interfere with Ras expression and function in mouse oocytes and early embryos. Microinjection of either ras antisense oligonucleotides or anti-Ras monoclonal antibody Y13-259 did not affect normal progression of oocytes through meiosis and arrest at metaphase II. However, microinjection of fertilized eggs with constructs expressing Ras N-17 inhibited subsequent development through the two-cell stage. This inhibitory effect of Ras N-17 was overcome by simultaneous injection of a plasmid expressing an active raf oncogene, indicating that it resulted from interference with the Ras/Raf signaling pathway. In contrast to the inhibition of two-cell embryo development resulting from microinjection of pronuclear stage eggs, microinjection of late two-cell embryos with Ras N-17 expression constructs did not affect subsequent cleavages and development to morulae and blastocysts. It thus appears that the Ras/Raf signaling pathway, presumably activated by autocrine growth factor stimulation, is specifically required at the two-cell stage, which is the time of transition between maternal and embryonic gene expression in mouse embryos. C1 DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. FAULKNER HOSP,FAULKNER CTR REPROD MED,BOSTON,MA 02115. FU NICHD NIH HHS [HD26594] NR 58 TC 21 Z9 21 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 1994 VL 14 IS 10 BP 6655 EP 6662 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PH031 UT WOS:A1994PH03100025 PM 7935384 ER PT J AU ABUSHAKRA, SR COLE, AJ ADAMS, RN DRACHMAN, DB AF ABUSHAKRA, SR COLE, AJ ADAMS, RN DRACHMAN, DB TI CHOLINERGIC STIMULATION OF SKELETAL-MUSCLE CELLS INDUCES RAPID IMMEDIATE-EARLY GENE-EXPRESSION - ROLE OF INTRACELLULAR CALCIUM SO MOLECULAR BRAIN RESEARCH LA English DT Article DE SKELETAL MUSCLE; IMMEDIATE EARLY GENE; ACETYLCHOLINE RECEPTOR; CALCIUM; INTRACELLULAR CALCIUM STORE; SYNAPTIC TRANSMISSION ID ACETYLCHOLINE-RECEPTORS; SARCOPLASMIC-RETICULUM; MESSENGER-RNA; RYANODINE RECEPTOR; RELEASE CHANNEL; GROWTH-FACTORS; ALPHA-SUBUNIT; MOUSE MUSCLE; C-FOS; CA-2+ AB Many properties of skeletal muscle are closely regulated by motor nerves. We have shown that nerve stimulation in vivo induced a rapid rise in mRNA for the immediate early gene (IEG) zif268 in stimulated muscle. However, the mechanisms leading to neural regulation of zif268 gene expression in muscle are not yet known. in this study, we used a mammalian skeletal muscle cell line (C2C12) to analyze the role of cholinergic transmission, and calcium flux, in the neural regulation of zif268. Treatment of the C2C12 muscle cells with carbachol, a cholinergic agonist, induced zif268 gene expression rapidly and transiently. This effect was blocked by alpha-bungarotoxin (alpha-BuTx), which specifically blocks nicotinic acetylcholine receptors. Treatment with ryanodine or dantrolene, which block the calcium release channel of the sarcoplasmic reticulum, inhibited the carbachol-induced zif268 response essentially completely. Calcium influx produced by A23187, a calcium ionophore, induced an increase of zif268 gene expression equivalent to the effect of carbachol stimulation. These results suggest that the effect of neural stimulation on zif268 may be attributable to cholinergic transmission, and the subsequent release of calcium from the sarcoplasmic reticulum. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. RP ABUSHAKRA, SR (reprint author), WAYNE STATE UNIV,SCH MED,DEPT NEUROL,4201 ST ANTOINE,6E-UHC,DETROIT,MI 48201, USA. FU NINDS NIH HHS [NS1370, R01 NS23719] NR 32 TC 14 Z9 14 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 1994 VL 26 IS 1-2 BP 55 EP 60 DI 10.1016/0169-328X(94)90073-6 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PL657 UT WOS:A1994PL65700007 PM 7854066 ER PT J AU BAGLEY, J DILLON, PJ ROSEN, C ROBINSON, J SODROSKI, J MARASCO, WA AF BAGLEY, J DILLON, PJ ROSEN, C ROBINSON, J SODROSKI, J MARASCO, WA TI STRUCTURAL CHARACTERIZATION OF BROADLY NEUTRALIZING HUMAN MONOCLONAL-ANTIBODIES AGAINST THE CD4 BINDING-SITE OF HIV-1 GP120 SO MOLECULAR IMMUNOLOGY LA English DT Article DE AIDS; PASSIVE IMMUNIZATION; VARIABLE REGION GENE SEGMENTS; B-CELL REPERTOIRE; COMPLEMENTARITY DETERMINING REGIONS (CDRS) ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNOGLOBULIN HEAVY-CHAIN; DNA-ASSOCIATED IDIOTYPE; PREFERENTIAL UTILIZATION; COMBINATORIAL LIBRARIES; ENVELOPE GLYCOPROTEIN; CD4-BINDING SITE; TYPE-1; GENES; VH AB The human monoclonal antibodies (mAbs) 15e and 21h are derived from HIV-1-infected individuals. They block CD4 binding, recognize conformation-dependent discontinuous epitopes on gp120 and neutralize a broad range of laboratory strains and primary isolates of HIV-1. To determine if a structural basis for neutralization could be identified, analysis of these CD4-binding site anti-gp120 human mAbs was performed, common features and differences were identified and a comparison was made with F105, a previously reported CD4-binding site anti-gp120 human mAb. The 15e and 21h mAb heavy chains are derived from different V region genes, i.e. V2-1 and VDP-35, which are members of the VHIV and VHIII families, respectively. Analysis of the genes encoding the heavy chain complementarity determining region (CDR) 3 revealed that both mAbs show a long D-H segment of similar size that could arise from D-D fusions of the dxp1/dlr1 and daudi/d22-12 germline DH genes along with use of the J(H6) and J(H5) germline segments. Similarly, the 15e and 21h light chains are derived from different V region genes, i.e. Hum01/012 and Hum1v318, that are members of the VkappaI and V(lambda)IIIa gene families, respectively. These V genes are rearranged with J(kappa1) and J(lambda2) germline genes. For both mAbs, the pattern of replacement mutations in the V region genes of the heavy and light chains is consistent with a process of somatic mutation and antigen-driven clonal selection. By comparing the CDRs of 15e, 21h and F105, eight positions in the rearranged heavy chains and two positions in the rearranged light chains were found to have identical amino acids. These studies suggest that there is no absolute restriction in the use of V region germline genes and form the foundation for understanding the humoral immune response to the CD4-binding site of gp120. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HUMAN GENOME SCI,ROCKVILLE,MD 20850. UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT,FARMINGTON,CT 06030. FU NCI NIH HHS [K08-CA01507]; NIAID NIH HHS [AI31783] NR 60 TC 28 Z9 28 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 1994 VL 31 IS 15 BP 1149 EP 1160 DI 10.1016/0161-5890(94)90029-9 PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA PN561 UT WOS:A1994PN56100004 PM 7935503 ER PT J AU SANDOR, T TIEMAN, J ONG, HT MOSS, MB JOLESZ, F ALBERT, M AF SANDOR, T TIEMAN, J ONG, HT MOSS, MB JOLESZ, F ALBERT, M TI COMPARISON OF THE PRECISION OF 2 STANDARDIZED COORDINATE SYSTEMS FOR THE QUANTITATION OF BRAIN ANATOMY - PRELIMINARY-RESULTS SO NEURORADIOLOGY LA English DT Article DE BRAIN; MAGNETIC RESONANCE IMAGING; LOCALIZATION ID POSITRON EMISSION TOMOGRAPHY; GLABELLA-INION LINE; COMPUTED-TOMOGRAPHY; CT; LOCALIZATION; DEMENTIA; IMAGES; PET AB We assessed reproducible definition of two standardized co-ordinate systems for intersubject analysis of brain images. The baselines in the two co-ordinate systems were a modification of the canthomeatal (mCM) line and the anterior-posterior commissural (AC-PC) line. Axial spin-echo MR images of four subjects at 1.5T were used. Operator error was computed from the replicate analyses of two operators. The mCM line was determined by the lens of the eye and the inter nai auditory canal, and the AC-PC line was determined by the intersection of the AC and PC with the interhemispheric fissure. Reproducibility of the mCM markers (SD = 0.59 mm) did not differ significantly from that of the AC-PC line (SD = 0.68 mm). The measurement error of the angle of the baseline (delta alpha), however, was more than 7 times as large for the AC-PC line as for the mCM line. An additional error affecting the rostrocaudal rotation of the co-ordinate systems, attributable to the distance between the anatomic markers, was 2.1 and 3.6 degrees (3 mm and 5 mm slice thickness) for the mCM co-ordinate system and 8.2 and 11.0 degrees (3 mm and 5 mm slice thickness) for the AC-PC system. The AC-PC line based co-ordinate system is therefore, less reproducible than the mCM line based system. This could be improved if a combination of axial and sagittal images were used for the definition of the AC-PC line. C1 BOSTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,BOSTON,MA 02118. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. RP SANDOR, T (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RADIOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIA NIH HHS [P01-AG04953] NR 19 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD OCT PY 1994 VL 36 IS 7 BP 499 EP 503 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA PL580 UT WOS:A1994PL58000001 PM 7845570 ER PT J AU PAKZABAN, P ISACSON, O AF PAKZABAN, P ISACSON, O TI NEURAL XENOTRANSPLANTATION - RECONSTRUCTION OF NEURONAL CIRCUITRY ACROSS SPECIES BARRIERS SO NEUROSCIENCE LA English DT Review ID MOUSE HIPPOCAMPAL TISSUE; FETAL DOPAMINE NEURONS; BLOOD-BRAIN-BARRIER; EMBRYONIC SEPTAL NUCLEI; CENTRAL-NERVOUS-SYSTEM; IA-ANTIGEN EXPRESSION; ADULT-RAT BRAIN; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; MESENCEPHALIC TISSUE AB Selective replacement of degenerated neurons in the adult brain with allogeneic fetal neuroblasts is a promising therapeutic modality for human neurodegenerative diseases, but is confounded with practical and potential ethical problems. To evaluate the potential of xenogeneic donors as a cell source for neural transplantation, we have critically examined the available experimental evidence in animal models pertaining to the survival, integration and function of xenogeneic fetal neuroblasts in the host brain. A statistical meta-analysis across multiple studies revealed that immunologically-related transplantation parameters (immunosuppression and donor-host phylogenetic distance) were the main determinants of neural xenograft survival. The immunological basis for xenograft rejection is reviewed in the context of novel immunoprotection strategies designed to enhance xenograft survival. Furthermore, the evidence for behavioral recovery based on anatomical and functional integration of neural xenografts in the host brain is examined with an awareness of developmental considerations. It is concluded that neural xenotransplantation offers a unique opportunity for effective neuronal replacement with significant potential for clinical use. C1 MCLEAN HOSP, 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, NEUROL SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, NEUROSCI PROGRAM, BOSTON, MA 02114 USA. FU NINDS NIH HHS [5T32 NS07340, NS29178, NS30064] NR 111 TC 85 Z9 87 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD OCT PY 1994 VL 62 IS 4 BP 989 EP 1001 DI 10.1016/0306-4522(94)90338-7 PG 13 WC Neurosciences SC Neurosciences & Neurology GA PN544 UT WOS:A1994PN54400003 PM 7845600 ER PT J AU HERMAN, LW FISCHMAN, AJ TOMPKINS, RG HANSON, RN BYON, C STRAUSS, HW ELMALEH, DR AF HERMAN, LW FISCHMAN, AJ TOMPKINS, RG HANSON, RN BYON, C STRAUSS, HW ELMALEH, DR TI THE USE OF PENTAFLUOROPHENYL DERIVATIVES FOR THE F-18 LABELING OF PROTEINS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY FRAGMENTS; FLUORIDES AB A simple, one-step method for the radiolabelling of proteins with F-18 is described. A series of pentafluorophenyl derivatives were synthesized and tested for F-18 exchange using tetrabutylammonium[F-18]fluoride in DMSO, with microwave heating. A number of the compounds examined incorporated F-18 quickly and in high yield. Two compounds, pentafluorobenzaldehyde and 2,3,5,6-tetrafluorophenyl-pentafluorobenzoate, were used to label HSA in good yield. The methods produce low specific activity labelled proteins, but are fast. The yields are reasonable and the reagents do not require a separate modification or activation step for protein labelling. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. NORTHEASTERN UNIV,MED CHEM SECT,BOSTON,MA 02115. NR 17 TC 34 Z9 35 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 1994 VL 21 IS 7 BP 1005 EP 1010 DI 10.1016/0969-8051(94)90091-4 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PL578 UT WOS:A1994PL57800014 PM 9234356 ER PT J AU FORCHIELLI, ML MCCOLL, R WALKER, WA LO, C AF FORCHIELLI, ML MCCOLL, R WALKER, WA LO, C TI CHILDREN WITH CONGENITAL HEART-DISEASE - A NUTRITION CHALLENGE SO NUTRITION REVIEWS LA English DT Review ID OXYGEN-CONSUMPTION; ENERGY-EXPENDITURE; GROWTH FAILURE; INFANTS; WEIGHT; BALANCE; THRIVE AB Growth in children with congenital heart disease (CHD) is often compromised. For several decades, investigators have tried to identify the factors affecting growth in children with CHD. Cardiac malformations are undoubtedly responsible for malnutrition, which may range from mild undernutrition to severe failure to thrive (FTT). Malnutrition may then significantly undermine the outcome of corrective surgical operations and postoperative recovery. Mechanisms linking CHD to malnutrition may be related either to decreased energy intake and/or to increased energy requirements. Decreased energy intake can involve deficiencies of specific nutrients, or insufficient total caloric intake. increased respiratory rate accompanying congestive heart failure may be responsible for increased energy requirements. Different types of cardiac malformations and consequent interventions may have different effects on growth and require diverse strategies. Most treatment strategies aim to facilitate ''catch-up'' growth, providing extra calories and protein that exceed the Recommended Dietary Allowance for age. However, there is no generally accepted set of guidelines that define appropriate caloric intake for catch-up growth. We attempt to identity the most important causes of malnutrition and highlight the most effective nutrition strategies for children with CHD. C1 MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. CHILDRENS HOSP,BOSTON,MA 02115. NR 42 TC 47 Z9 48 U1 1 U2 9 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD OCT PY 1994 VL 52 IS 10 BP 348 EP 353 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PQ559 UT WOS:A1994PQ55900003 PM 7816352 ER PT J AU KHARBANDA, S YUAN, ZM TANEJA, N WEICHSELBAUM, R KUFE, D AF KHARBANDA, S YUAN, ZM TANEJA, N WEICHSELBAUM, R KUFE, D TI P56/P53(LYN) TYROSINE KINASE ACTIVATION IN MAMMALIAN-CELLS TREATED WITH MITOMYCIN-C SO ONCOGENE LA English DT Article ID DNA-BINDING PROTEINS; PHOSPHATIDYLINOSITOL 3-KINASE; NITROGEN-MUSTARD; LYMPHOCYTES-B; CROSS-LINKING; MEMBRANE IMMUNOGLOBULIN; PHOSPHORYLATION; MECHANISM; P34CDC2; DAMAGE AB The present studies have examined the effects of mitomycin C (MMC), a genotoxic alkylating agent, on the activation of Src-like protein tyrosine kinases in HL-60 myeloid leukemia cells. The results demonstrate no detectable induction of p59/(fyn) or pp60(c-src) activity. The response of HL-60 cells to MMC however was associated with rapid activation of p56/p53(lyn). Similar findings were obtained with other alkylating agents such as nitrogen mustard and cis-platinum. Activation of p56/p53(lyn) was associated with increased autophosphorylation on tyrosine and sensitivity to the tyrosine kinase inhibitors herbimycin A and genistein. Studies with a glutathione S-transferase-Lyn fusion protein were performed to explore the potential significance of p56/p53(lyn) activation. Analysis of the adsorbates demonstrates interaction of Lyn with the cell cycle regulatory protein, p34(cdc2). Coimmunoprecipitation studies further confirmed the association of p56/p53(lyn) and p34(cdc2) in MMC-treated cells. We also demonstrate that p34(cdc2) undergoes increased phosphorylation on tyrosine following MMC exposure and that p56/p53(lyn) phosphorylates the Tyr-15 site of p34(cdc2)in vitro. These findings indicate that the cellular response to MMC includes activation of p56/p53(lyn) and that this event may contribute to signals transduced by the DNA damage-dependent mitotic checkpoint. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA19589] NR 50 TC 36 Z9 36 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT PY 1994 VL 9 IS 10 BP 3005 EP 3011 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PG822 UT WOS:A1994PG82200028 PM 8084605 ER PT J AU RUBIN, PAD BILYK, JR SHORE, JW AF RUBIN, PAD BILYK, JR SHORE, JW TI ORBITAL RECONSTRUCTION USING POROUS POLYETHYLENE SHEETS SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Academy-of-Ophthalmology Annual Meeting CY NOV, 1993 CL CHICAGO, IL SP AMER ACAD OPHTHALMOL ID FLOOR FRACTURE REPAIR; BONE-GRAFTS; IMPLANT; ENOPHTHALMOS; HYDROXYLAPATITE; HYDROXYAPATITE; INFECTION; FIXATION; SURGERY; BLOCKS AB Background: There has been growing interest in using porous alloplastic implants for reconstructive orbital surgery because of their perceived increased biocompatibility. One commercially available porous implant is high-density porous polyethylene (Medpor). It is made of pure particles of polyethylene that form interconnecting pores and have excellent handling characteristics. Methods: The authors performed 37 orbital reconstructions using 0.85-, 1.5-, or 3-mm porous polyethylene sheets to reconstruct internal orbital defects. Mean postoperative follow-up was 18.5 months. Four patients were treated for anophthalmic enophthalmos; there was one patient with spontaneous enophthalmos. In selected patients, other implants also were used, including miniplates or microplates, silastic sheets, autologous bone, or nasal septal cartilage. In patients with enophthalmos, the implants were stacked to reverse the malposition evident at surgery. Results: Preoperatively, 27 patients had symptomatic diplopia. Postoperatively, the diplopia resolved in 15 patients and decreased in 7. No patients had induced diplopia or exacerbation of preoperative diplopia. Enophthalmos resolved in 9 of 18 patients. Hypoglobus was normalized in nine of nine patients. There was one major complication of orbital infection requiring explantation 1 week postoperatively. Minor complications included undercorrection, a symptomatically palpable implant, and transient postoperative chemosis. Conclusion: Porous polyethylene sheets offer several distinct advantages when used for orbital reconstruction. They are easy to handle, shape, contour, position, fixate, and use with other autogenous and alloplastic implants. In this series, these sheets permitted predictable, stable results with few complications. RP RUBIN, PAD (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,EYE PLAST & ORBIT SERV,BOSTON,MA 02114, USA. NR 35 TC 119 Z9 124 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 1994 VL 101 IS 10 BP 1697 EP 1708 PG 12 WC Ophthalmology SC Ophthalmology GA PL942 UT WOS:A1994PL94200016 PM 7936569 ER PT J AU EASTCOTT, JW YAMASHITA, K TAUBMAN, MA HARADA, Y SMITH, DJ AF EASTCOTT, JW YAMASHITA, K TAUBMAN, MA HARADA, Y SMITH, DJ TI ADOPTIVE TRANSFER OF CLONED T-HELPER CELLS AMELIORATES PERIODONTAL-DISEASE IN NUDE RATS SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE LYMPHOCYTE TRANSFER; T CELL CLONE; PERIODONTAL DISEASE; RAT; ACTINOBACILLUS ACTINOMYCETEMCOMITANS ID HUMAN IMMUNE-RESPONSES; LOCALIZED JUVENILE PERIODONTITIS; CREVICULAR FLUID ANTIBODY; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ORAL MICROORGANISMS; BONE LOSS; SPECIFICITY; IMMUNOGLOBULINS; ASSOCIATION; LYMPHOCYTES AB We have previously described a T helper cell 2-type clone, A3, of rat T cells that provides help for antibody production to Actinobacillus actinomycetemcomitans in vitro and in vivo in normal (euthymic) isogeneic Rowett strain recipient rats. Adoptive transfer of this T helper cell clone to euthymic rats also protects them from periodontal bone loss induced by oral infection with A. actinomycetemcomitans. In the present study, to assess the cell requirement for protection, A3 clone T lymphocytes (10(6)) or naive lymph node (6 x 10(4)) T cells, or A3 plus naive lymph node T cells (6 x 10(4)) were adoptively transferred to groups (n = 7-9) of 30-day-old Rowett athymic nude (rnu/rnu) rats. All recipients were also immunized (intraperitoneally) with 10(7) killed A. actinomycetemcomitans on the day of T cell transfer and orally infected with these bacteria on each of the next 5 days. Recipients of the combined A3 + lymph node T cell transfer showed significantly increased serum immunoglobulin G (IgG) and IgM antibody to A. actinomycetemcomitans and in vitro proliferation of spleen lymphocytes to A. actinomycetemcomitans as antigen compared with nude animals receiving lymph node T cells only. Although other possibilities are discussed, we inferred that these differences might be due to successful population of the congenitally athymic rats by A3 clone cells given with a small number of normal autologous naive lymph node T cells. The result of this co-transfer of naive T cells with the A3 clone cells seemed to be greatly increased antibody production and protection from periodontal bone loss. C1 FORSYTH DENT CTR,DEPT IMMUNOL,BOSTON,MA 02115. NR 34 TC 55 Z9 56 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD OCT PY 1994 VL 9 IS 5 BP 284 EP 289 DI 10.1111/j.1399-302X.1994.tb00072.x PG 6 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA PK278 UT WOS:A1994PK27800005 PM 7808770 ER PT J AU STASHENKO, P WANG, CY TANIISHII, N YU, SM AF STASHENKO, P WANG, CY TANIISHII, N YU, SM TI PATHOGENESIS OF INDUCED RAT PERIAPICAL LESIONS SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article; Proceedings Paper CT Symposium on Endodontic Biology CY OCT 04-05, 1993 CL FARMINGTON, CT SP UNIV CONNECTICUT ID BONE-RESORBING ACTIVITY; INFLAMMATORY CELLS; FORMATION INVITRO; RESORPTION; INTERLEUKIN-1-BETA; IDENTIFICATION; CYTOKINES AB Studies of the mechanisms of pathogenesis of periapical lesions were undertaken using a rat model of surgical pulp exposure. In this model, periapical lesions develop rapidly between days 0 and 15 (active phase) and more slowly thereafter (chronic phase). A Gram-negative anaerobic flora, similar to that seen in human beings, are quickly established. Lesions contain a mixed inflammatory cell infiltrate consisting of T cells, neutrophils, B cells, macrophages, and plasma cells. Helper T cells predominate during the active phase, whereas suppressor T cells are more frequent in the chronic phase. Extracts of periapical lesions contain bone-resorbing activity, the highest levels of which are present when lesions are actively expanding. Most bone-resorbing activity is mediated by the cytokine interleukin-1alpha, as determined by biochemical criteria and antibody neutralization studies. Prostaglandin2 accounts for 10% to 15% of resorptive activity. Cells that express interleukin-1alpha were identified in pulp beginning on day 2 after exposure and in periapical tissue beginning on day 7, as determined by in situ hybridization and immunostaining. Macrophages, fibroblasts, neutrophils, and osteoclasts were positive for interleukin-1alpha mRNA and protein. Cells that express tumor necrosis factor alpha were also detected, whereas cells expressing interleukin-1beta or tumor necrosis factor beta were absent. Finally, periapical bone destruction was inhibited by 60% by treatment with interleukin-1 receptor antagonist. These studies establish a key role for interleukin-1alpha in the pathogenesis of periapical lesions in the rat model. C1 KANAGAWA DENT COLL,DEPT ENDODONT,KANAGAWA,JAPAN. HARVARD UNIV,SCH DENT MED,DEPT ENDODONT,CAMBRIDGE,MA 02138. RP STASHENKO, P (reprint author), FORSYTH DENT CTR,DEPT CYTOKINE BIOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-09018] NR 36 TC 78 Z9 81 U1 0 U2 3 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 1994 VL 78 IS 4 BP 494 EP 502 DI 10.1016/0030-4220(94)90044-2 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PL940 UT WOS:A1994PL94000018 PM 7800381 ER PT J AU LHOWE, DW AF LHOWE, DW TI OPEN FRACTURES OF THE FEMORAL-SHAFT SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID FIXATION; COMPLICATIONS; STABILIZATION; PLATE AB In this article, the treatment of open fractures of the femoral shaft is discussed, and the available clinical studies are reviewed. A rationale for treating these types of fractures is provided, and specific recommendations are made. RP LHOWE, DW (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPED TRAUMA SERV,275 CAMBRIDGE ST,SUITE 403,BOSTON,MA 02114, USA. NR 24 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 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD OCT PY 1994 VL 25 IS 4 BP 573 EP & PG 0 WC Orthopedics SC Orthopedics GA PK750 UT WOS:A1994PK75000003 PM 8090471 ER PT J AU FLEISCHMAN, AR NOLAN, K DUBLER, NN EPSTEIN, MF GERBEN, MA JELLINEK, MS LITT, IF MILES, MS OPPENHEIMER, S SHAW, A VANEYS, J VAUGHAN, VC AF FLEISCHMAN, AR NOLAN, K DUBLER, NN EPSTEIN, MF GERBEN, MA JELLINEK, MS LITT, IF MILES, MS OPPENHEIMER, S SHAW, A VANEYS, J VAUGHAN, VC TI CARING FOR GRAVELY ILL CHILDREN SO PEDIATRICS LA English DT Article DE DECISION-MAKING; QUALITY OF LIFE; PARENTAL DISCRETION; ADOLESCENT AUTONOMY; END OF LIFE ILL CHILDREN ID PHYSICIANS RESPONSIBILITY; ETHICS AB Background. Much has been written about the care of the hopelessly ill adult, but there is little guidance for pediatric health care professionals in the management of children who are critically or terminally ill. Methods. Through a 3-day meeting in Tarrytown,NY, attended by a group of pediatricians and others directly involved in these issues, a principled approach was developed for the treatment of, and health care decisionmaking for, children who are gravely ill. Results. The group agreed that the needs and interests of the child must be the central focus of any treatment plan and that the child should be involved to as great extent possible, consistent with developmental maturity, in the decision-making process. Quality of future life should be viewed as being relevant in all decisions. Parents are believed to be the natural guardians of children and ought to have great latitude in making decisions for them. However, parental discretion is not absolute and professionals must maintain an independent obligation to protect the child's interests. Conclusions. Decision-making should be collaborative among patient, parents, and professionals. When conflict arises, consultation and ethics committees may assist in resolution. When cure or restoration of function is no longer possible, or reasonable, promotion of comfort becomes the primary goal of management. Optimal use of pain medication and compassionate concern for the physical, psychological, and spiritual well-being of the child and family should be the primary focus of the professionals caring for the dying child. C1 MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL & SOCIAL MED,BRONX,NY 10467. HASTINGS CTR,BRIARCLIFF MANOR,NY. CHILDRENS HOSP,BOSTON,MA 02115. CHILDRENS HOSP,BERWYN,PA. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT PEDIAT,BOSTON,MA 02114. STANFORD UNIV,MED CTR,SCH MED,DEPT PEDIAT,STANFORD,CA 94305. UNIV N CAROLINA,SCH NURSING,DEPT WOMENS & CHILDRENS HLTH,CHAPEL HILL,NC. UNIV CINCINNATI,CHILDRENS HOSP,MED CTR,DEPT PEDIAT,CINCINNATI,OH. UNIV CALIF LOS ANGELES,SCH MED,OLIVE VIEW UCLA MED CTR,DEPT PEDIAT SURG,SYLMAR,CA. UNIV TEXAS,SCH MED,DEPT PEDIAT,HOUSTON,TX. STANFORD UNIV,MED CTR,SCH MED,DEPT PEDIAT,STANFORD,CA 94305. NR 21 TC 40 Z9 41 U1 0 U2 3 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 1994 VL 94 IS 4 BP 433 EP 439 PN 1 PG 7 WC Pediatrics SC Pediatrics GA PK840 UT WOS:A1994PK84000004 PM 7936849 ER PT J AU REDMOND, RW SRICHAI, MB BILITZ, JM SCHLOMER, DD KRIEG, M AF REDMOND, RW SRICHAI, MB BILITZ, JM SCHLOMER, DD KRIEG, M TI MEROCYANINE DYES - EFFECT OF STRUCTURAL MODIFICATIONS ON PHOTOPHYSICAL PROPERTIES AND BIOLOGICAL-ACTIVITY SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SINGLET-OXYGEN PRODUCTION; ENERGY-TRANSFER; 3,3'-DIALKYLTHIACARBOCYANINE DYES; 540-SENSITIZED PHOTOINACTIVATION; 540-MEDIATED PHOTOSENSITIZATION; MEDIATED PHOTOLYSIS; MOLECULAR-OXYGEN; LEUKEMIC-CELLS; QUANTUM YIELD; INACTIVATION AB Merocyanine derivatives were prepared by structural alterations at the barbituric acid or chalcogenazole moieties. The photophysical properties of the dyes were markedly influenced by the presence of selenium rather than sulfur as a substituent at position 2 of the barbiturate. In methanol, quantum yields of both triplet state Phi(T)) and singlet oxygen sensitization (Phi(Delta) were increased by over an order of magnitude, with a concomitant decrease in fluorescence, when selenium was present in the molecule. Photoisomerization, one of the dominant deactivation pathways in the sulfur- or oxygen-containing analogues, was completely absent in the selenium-containing derivatives. Efficient triplet state formation was observed for selenium-containing derivatives incorporated into L1210 cells by diffuse reflectance laser Bash photolysis. Cytotoxicity studies, carried out using clonogenic assays on L1210 leukemia cells, showed a good correlation with Phi(T) and Phi(Delta), measured in solution. Experimental evidence provided by this paper supports a triplet state-, and probably singlet oxygen-, mediated phototoxic mechanism. Photoisomerization or singlet state mechanisms can be discounted. C1 MED COLL WISCONSIN,MACC FUND RES CTR,DEPT PEDIAT,MILWAUKEE,WI 53226. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN PHOTOMED LAB,BOSTON,MA 02114. FU NCI NIH HHS [NCI CA50733] NR 46 TC 44 Z9 44 U1 1 U2 6 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 1994 VL 60 IS 4 BP 348 EP 355 DI 10.1111/j.1751-1097.1994.tb05114.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PL411 UT WOS:A1994PL41100008 PM 7527561 ER PT J AU VITKIN, IA WILSON, BC ANDERSON, RR PRAHL, SA AF VITKIN, IA WILSON, BC ANDERSON, RR PRAHL, SA TI PULSED PHOTOTHERMAL RADIOMETRY IN OPTICALLY TRANSPARENT MEDIA CONTAINING DISCRETE OPTICAL ABSORBERS SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID SWITCHED RUBY-LASER; REFRACTIVE-INDEX; CONDUCTION; RADIATION; MELANIN; TATTOOS; CARBON AB A description of heat transport by conduction and radiation in inhomogeneous materials following absorption of a brief optical pulse is presented, and investigated experimentally using pulsed photothermal radiometry (PPTR). The model indicates that the role of radiation as an intramedium heat transfer modality increases with increasing temperatures and decreasing infrared (IR) absorption of the medium. However, for the range of conditions analysed in this study, conductive transfer dominates. Thus, the inclusion of radiation does not significantly perturb the internal temperature profiles, although it does influence the radiometric emission from the sample, and hence the PPTR signal. The thermal confinement effects described in this study may be relevant in photomedicine, for example in pulsed laser irradiation of tissues containing small absorbing targets. C1 MCMASTER UNIV,HAMILTON L8V 1C3,ON,CANADA. PRINCESS MARGARET HOSP,ONTARIO CANC INST,DEPT CLIN PHYS,TORONTO M4X 1K9,ON,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO M4X 1K9,ON,CANADA. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. OREGON GRAD INST,DEPT ELECT ENGN & APPL PHYS,PORTLAND,OR 97271. RP VITKIN, IA (reprint author), HAMILTON REG CANC CTR,DEPT MED PHYS,HAMILTON L8V 1C3,ON,CANADA. RI Vitkin, Alex/I-8166-2012 NR 37 TC 6 Z9 6 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TECHNO HOUSE, REDCLIFFE WAY, BRISTOL, ENGLAND BS1 6NX SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT PY 1994 VL 39 IS 10 BP 1721 EP 1744 DI 10.1088/0031-9155/39/10/014 PG 24 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA PK957 UT WOS:A1994PK95700014 PM 15551541 ER PT J AU HEDIGER, MA RHOADS, DB AF HEDIGER, MA RHOADS, DB TI MOLECULAR PHYSIOLOGY OF SODIUM-GLUCOSE COTRANSPORTERS SO PHYSIOLOGICAL REVIEWS LA English DT Review ID BRUSH-BORDER-MEMBRANE; EPITHELIAL-CELL LINE; DEPENDENT HEXOSE-TRANSPORT; INTESTINAL NUTRIENT TRANSPORTERS; CHRONICALLY DIABETIC RATS; PROLINE SYMPORT CARRIER; COLON CANCER-CELLS; SUGAR-TRANSPORT; NA+/GLUCOSE COTRANSPORTER; ESCHERICHIA-COLI C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,TUMOR BIOL LAB,BOSTON,MA. RP HEDIGER, MA (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK-43171, DK-01392, DK-43632] NR 210 TC 289 Z9 297 U1 1 U2 11 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD OCT PY 1994 VL 74 IS 4 BP 993 EP 1026 PG 34 WC Physiology SC Physiology GA PM776 UT WOS:A1994PM77600005 PM 7938229 ER PT J AU VINK, J DEKKER, SK VANLEEUWEN, RL VERMEER, BJ BRUIJN, JA BYERS, HR AF VINK, J DEKKER, SK VANLEEUWEN, RL VERMEER, BJ BRUIJN, JA BYERS, HR TI ROLE OF BETA-1 INTEGRINS IN CELL SPREADING AND MIGRATION OF HUMAN NEVOMELANOCYTES AND DYSPLASTIC NEVI CELLS ON COLLAGEN TYPE-IV AND LAMININ SO PIGMENT CELL RESEARCH LA English DT Article; Proceedings Paper CT XVth International Pigment Cell Conference CY SEP 26-30, 1993 CL LONDON, ENGLAND SP INT FEDERAT PIGMENT CELL RES DE NEVOMELANOCYTES; DYSPLASTIC NEVI; CELL SPREADING; CELL MIGRATION; INTEGRINS; EXTRACELLULAR MATRIX ID CUTANEOUS MALIGNANT-MELANOMA; K MOLE SYNDROME; EXTRACELLULAR-MATRIX; MONOCLONAL-ANTIBODY; TUMOR PROGRESSION; SURFACE RECEPTORS; ADHESION; EXPRESSION; ASSOCIATION; MELANOCYTES AB We characterized pi integrin subunit expression on three different cultures of benign human nevomelanocytes (NMC) and on four different cell cultures of human dysplastic nevus (DN) cells by flow cytometry analysis and examined their role in mediating cell spreading and migration on collagen type IV (CN IV) and laminin (LN) coated substrates by using a quantitative video image analysis system. The seven human NMC and DNC cultures expressed heterogeneous levels of beta 1, alpha 2, alpha 3 and alpha 6 integrin subunits. Image analysis showed that a significant increase (P<0.001) in cell spreading and migration of the DN cells was induced on increasing coating concentrations of CN IV and LN. However, the NMC did not show an increase in cell spreading or migration on these substrates when compared to the substrates coated with denatured BSA only. The CN IV-induced cell spreading of the DN cells was significantly inhibited by anti-pr mAb (AIIB2), anti-alpha 2 mAb (P1E6), or anti-alpha 3 mAb (P1B5), but not by mAb against alpha 6 integrin subunit (GoH3). The DN cell spreading an LN was not significantly inhibited by these mAbs. In contrast, the migration of the DN on CN IV and LN was significantly inhibited by anti-beta 1 mAb, anti-alpha 2 mAb, anti-alpha 2 mAb and anti-alpha 3 mAb. These data suggest that the alpha 2 and alpha 3 subunit are important for cell spreading of the DN on CN Iq although they are less important in cell spreading on the extracellular matrix component LN. The alpha 2, alpha 3, and alpha 6 integrin subunits are important for the migration of DN cells on both CN IV and LN. C1 LEIDEN UNIV,DEPT DERMATOL & PATHOL,LEIDEN,NETHERLANDS. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,DIV DERMATOPATHOL,BOSTON,MA 02144. FU NCI NIH HHS [CA-45587] NR 46 TC 7 Z9 7 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD OCT PY 1994 VL 7 IS 5 BP 339 EP 347 DI 10.1111/j.1600-0749.1994.tb00637.x PG 9 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA PW151 UT WOS:A1994PW15100011 PM 7533906 ER PT J AU KIM, WS VACANTI, CA UPTON, J VACANTI, JP AF KIM, WS VACANTI, CA UPTON, J VACANTI, JP TI BONE DEFECT REPAIR WITH TISSUE-ENGINEERED CARTILAGE SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID DNA-REPLICATION; ANTIBODY AB We tested the efficacy of a new approach for the tissue-engineered growth of cartilage developed in our laboratory in repairing surgically created bone defects in the craniums of rats. Large cranial defects were created bilaterally in the frontoparietotemporal bones of athymic nude rats (n = 10). There was gross evidence of new cartilage in 8 of 10 experimental defects that had been filled with a synthetic biocompatible, biodegradable polymer template that had been seeded in vitro with freshly isolated chondrocytes. The control defects, filled with either nothing at all or a polymer template without chondrocytes, showed no evidence of cartilaginous repair (0 of 10). Statistical analysis using McNemar's test with pooled samples showed significant differences between the two groups (p<0.05). Prior reports concerning the biologic repair of bony defects involved stimulation of adjacent mesenchymal tissue and resulted in ingrowth of new bone. To our knowledge, this is the first report of structural cartilaginous repair of a bony defect with matrix secreted by implanted chondrocytes. C1 HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,BOSTON,MA. BETH ISRAEL HOSP,DEPT PLAST SURG,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. RP KIM, WS (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,WHITE 5,BOSTON,MA 02114, USA. NR 15 TC 24 Z9 32 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD OCT PY 1994 VL 94 IS 5 BP 580 EP 584 DI 10.1097/00006534-199410000-00002 PG 5 WC Surgery SC Surgery GA PK556 UT WOS:A1994PK55600002 PM 7938279 ER PT J AU ZELOP, C BENACERRAF, BR AF ZELOP, C BENACERRAF, BR TI THE CAUSES AND NATURAL-HISTORY OF FETAL ASCITES SO PRENATAL DIAGNOSIS LA English DT Article DE FETAL ASCITES; FETUS; ULTRASOUND; FETAL ANOMALIES ID NONIMMUNE HYDROPS-FETALIS; SONOGRAPHIC EVALUATION; MECONIUM PERITONITIS; INFECTION; ULTRASOUND; DIAGNOSIS AB The purpose of this study was to examine the natural history and differential diagnosis of ultrasound-detected, isolated fetal ascites. Retrospective review of our patient data base, from 1989 to 1993, revealed 18 patients with fetal ascites diagnosed sonographically. Fetuses presenting with generalized hydrops were excluded. One of the 18 fetuses with ascites had a chromosomal abnormality (trisomy 21), four fetuses had intrauterine infections, seven had gastrointestinal processes, two had genitourinary tract abnormalities, and four were labelled as 'idiopathic' (all four resulting in normal neonates). Seventeen of 18 fetuses survived; there was one fetal demise secondary to active syphilis. One fetus with parvovirus infection required intrauterine transfusion and did well. Two infants are developmentally retarded, including one with trisomy 21 and one with microcephaly secondary to cytomegalovirus infection. Fourteen of 18 fetuses had documented in-utero resolution of the ascites. Eleven of the 18 were associated with polyhydramnios sometime during fetal life. None of the fetuses developed hydrops. In conclusion, fetal ascites can result from many different aetiologies, including gastrointestinal and genitourinary anomalies. Chromosomal abnormalities and viral aetiologies must also be considered. Fetuses who have isolated ascites can have a good outcome with resolution of the ascites antenatally. C1 BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 16 TC 32 Z9 34 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD OCT PY 1994 VL 14 IS 10 BP 941 EP 946 DI 10.1002/pd.1970141008 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA PQ140 UT WOS:A1994PQ14000007 PM 7899269 ER PT J AU CUMMINGS, JL AF CUMMINGS, JL TI DEPRESSION IN NEUROLOGIC DISEASES SO PSYCHIATRIC ANNALS LA English DT Article ID STROKE C1 UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, PSYCHIAT SERV, BEHAV NEUROSCI SECT, LOS ANGELES, CA USA. NR 25 TC 8 Z9 8 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 1994 VL 24 IS 10 BP 525 EP 531 PG 7 WC Psychiatry SC Psychiatry GA PP675 UT WOS:A1994PP67500006 ER PT J AU CASTELLON, SA ASARNOW, RF GOLDSTEIN, MJ MARDER, SR AF CASTELLON, SA ASARNOW, RF GOLDSTEIN, MJ MARDER, SR TI PERSISTING NEGATIVE SYMPTOMS AND INFORMATION-PROCESSING DEFICITS IN SCHIZOPHRENIA - IMPLICATIONS FOR SUBTYPING SO PSYCHIATRY RESEARCH LA English DT Article DE SPAN OF APPREHENSION TEST; PROGNOSIS; DEFICIT SYNDROME OF SCHIZOPHRENIA; ATTENTION ID POSITIVE SYMPTOMS; NONDEFICIT FORMS; BACKWARD-MASKING; VULNERABILITY; FLUPHENAZINE; DEFINITION AB To test the hypothesis that schizophrenic patients with persisting negative symptoms have stable information-processing impairments compared with schizophrenic patients without persisting negative symptoms, 20 chronic schizophrenic outpatients were trichotomously subgrouped on the basis of the level of negative symptoms that they displayed across multiple rating periods over a 1-year period. Brief Psychiatric Rating Scale assessments of negative symptoms were used to assign subjects into either an operationally defined persisting negative symptom (PNS), transient negative symptom (TNS), or no negative symptom (NNS) subgroup. The level and pattern of these subgroups' performance on a visual information-processing task, the Span of Apprehension Test (SPAN), were compared. Although the three groups did not differ statistically in level of SPAN performance during a drug-free baseline, the PNS group had significantly poorer SPAN performance than the other two groups at the 1-year followup assessment. The SPAN performance of the TNS and NNS groups improved while the SPAN performance of the PNS group did not improve over the 1-year followup period. C1 UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT PSYCHOL,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV,PSYCHIAT SPECIAL PROGRAMS,LOS ANGELES,CA. FU NIMH NIH HHS [MH-45112] NR 31 TC 7 Z9 8 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 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD OCT PY 1994 VL 54 IS 1 BP 59 EP 69 DI 10.1016/0165-1781(94)90065-5 PG 11 WC Psychiatry SC Psychiatry GA QC481 UT WOS:A1994QC48100006 PM 7701029 ER PT J AU FRUEH, BC MIRABELLA, RF CHOBOT, K FOSSEY, MD AF FRUEH, BC MIRABELLA, RF CHOBOT, K FOSSEY, MD TI CHRONICITY OF SYMPTOMS IN COMBAT VETERANS WITH PTSD TREATED BY THE VA MENTAL-HEALTH SYSTEM SO PSYCHOLOGICAL REPORTS LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY OCT 24-27, 1993 CL SAN ANTONIO, TX SP Int Soc Traumat Stress Studies ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM COMBAT; RELIABILITY; VALIDITY; SCALE AB Self-report questionnaire data, collected at two stages of treatment, are presented for a group of 40 combat veterans with PTSD treated within the VA mental health system. Patients completed the Beck Depression Inventory, Mississippi Scale, and Dissociative Experiences Scale prior to treatment at a PTSD outpatient clinic and at midtreatment follow-up. Patients' symptom reports at follow-up were not correlated with length of time in treatment. Further, results suggest that patients' self-reported symptoms on these measures do not show evidence of improvement after entry into the VA mental health system. Explanations for this apparent chronicity of symptoms are discussed. RP FRUEH, BC (reprint author), RALPH H JOHNSON VET AFFAIRS MED CTR,PSYCHOL SERV 116B,109 BEE ST,CHARLESTON,SC 29401, USA. NR 20 TC 9 Z9 9 U1 1 U2 1 PU PSYCHOLOGICAL REPORTS PI MISSOULA PA P O BOX 9229, MISSOULA, MT 59807 SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD OCT PY 1994 VL 75 IS 2 BP 843 EP 848 PG 6 WC Psychology, Multidisciplinary SC Psychology GA PR104 UT WOS:A1994PR10400024 PM 7862794 ER PT J AU MCFARLAND, EG MAYOSMITH, WW SAINI, S HAHN, PF GOLDBERG, MA LEE, MJ AF MCFARLAND, EG MAYOSMITH, WW SAINI, S HAHN, PF GOLDBERG, MA LEE, MJ TI HEPATIC HEMANGIOMAS AND MALIGNANT-TUMORS - IMPROVED DIFFERENTIATION WITH HEAVILY T2-WEIGHTED CONVENTIONAL SPIN-ECHO MR-IMAGING SO RADIOLOGY LA English DT Article DE ANGIOMA, GASTROINTESTINAL TRACT; LIVER NEOPLASMS, MR ID SMALL CAVERNOUS HEMANGIOMA; HEPATOCELLULAR-CARCINOMA; T2 VALUES; LIVER; METASTASES; LESIONS; 1.5-T; OPTIMIZATION; DIAGNOSIS; FLASH AB PURPOSE: To determine whether hemangiomas and malignant tumors can be better differentiated at 1.5-T magnetic resonance imaging with use of more heavily T2-weighted conventional spin-echo sequences. MATERIALS AND METHODS: Eighty-three patients with focal liver lesions (50 malignant tumors, 24 hemangiomas, nine cysts) larger than 1 cm were studied with a 3,000/80,160 sequence (repetition time msec/echo time [TE] msec). T2 relaxation times and lesion/liver signal intensity ratios at TEs of 80 and 160 msec were measured. Receiver operating characteristic (ROC) analyses of expert readers and quantitative measures were performed. RESULTS: T2 relaxation times demonstrated the best performance in distinguishing hemangiomas from malignant tumors (area under ROC curve = .99 +/- .01). Mean T2 times were 76 msec +/- 11 for malignant tumors, 142 msec +/- 40 for hemangiomas, and 341 msec +/- 38 for cysts. A cutoff T2 value of 112 msec allowed discrimination between hemangiomas and malignant tumors with a 97% accuracy, 100% sensitivity, and 92% specificity. CONCLUSION: Hemangiomas and malignant tumors are better differentiated with use of T2 relaxation times obtained with a more heavily T2-weighted sequence. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 30 TC 137 Z9 143 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 1994 VL 193 IS 1 BP 43 EP 47 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH229 UT WOS:A1994PH22900014 PM 8090920 ER PT J AU MITCHELL, DG SAINI, S WEINREB, J DELANGE, EE RUNGE, VM KUHLMAN, JE PARISKY, Y JOHNSON, CD BROWN, JJ SCHNALL, M HERFKENS, RJ DAVIS, PL GORCZYCA, D SICA, G FOSTER, GS BERNARDINO, ME AF MITCHELL, DG SAINI, S WEINREB, J DELANGE, EE RUNGE, VM KUHLMAN, JE PARISKY, Y JOHNSON, CD BROWN, JJ SCHNALL, M HERFKENS, RJ DAVIS, PL GORCZYCA, D SICA, G FOSTER, GS BERNARDINO, ME TI HEPATIC METASTASES AND CAVERNOUS HEMANGIOMAS - DISTINCTION WITH STANDARD-DOSE AND TRIPLE-DOSE GADOTERIDOL-ENHANCED MR-IMAGING SO RADIOLOGY LA English DT Article DE ANGIOMA, GASTROINTESTINAL SYSTEM; GADOLINIUM; LIVER NEOPLASMS, DIAGNOSIS; LIVER NEOPLASMS, SECONDARY; MAGNETIC RESONANCE (MR), PULSE SEQUENCES; MAGNETIC RESONANCE (MR), TISSUE CHARACTERIZATION ID SPIN-ECHO; COMPUTED-TOMOGRAPHY; LIVER-LESIONS; TISSUE CONCENTRATION; DELAYED ENHANCEMENT; SIGNAL INTENSITY; GD-DTPA; CT; DIFFERENTIATION; TUMORS AB PURPOSE: To determine if hepatic metastases can be distinguished from cavernous hemangiomas by pattern analysis pf magnetic resonance (MR) images obtained prior to and following administration of gadoteridol at standard (0.1 mmol/kg) and triple (0.3 mmol/kg) doses. MATERIALS AND METHODS: Ninety-five patients with proved hepatic metastases (n = 71) or cavernous hemangiomas (n = 24) underwent MR imaging at 16 different institutions. T2-weighted spin-echo and T1-weighted images were obtained before and after gadoteridol administration. Two independent blinded reviewers rated individual features of benignancy versus malignancy on a five-point confidence scale. RESULTS: The most useful diagnostic features, with 100% specificity, were nodular enhancement for hemangiomas and rim enhancement for metastases. Confident (definitely benign or definitely malignant) diagnoses were rendered in 80 of 95 cases (84%), with an accuracy of a confident diagnosis of 96%. CONCLUSION: The pattern of enhancement on T1-weighted images is highly accurate for distinction between hemangiomas and metastases in images obtained with both doses. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT RADIOL,PHILADELPHIA,PA 19107. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV VIRGINIA HOSP,CHARLOTTESVILLE,VA. UNIV KENTUCKY,ALBERT B CHANDLER MED CTR,LEXINGTON,KY 40536. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21205. UNIV SO CALIF,MED CTR,LOS ANGELES,CA. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. EDWARD MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. HOSP UNIV PENN,PHILADELPHIA,PA 19104. STANFORD UNIV,MED CTR,STANFORD,CA 94305. PITTSBURGH NMR INST,PITTSBURGH,PA. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. EMORY UNIV HOSP,ATLANTA,GA 30322. RP MITCHELL, DG (reprint author), THOMAS JEFFERSON UNIV HOSP,DEPT RADIOL,1096 MAIN BLDG,132 S 10TH ST,PHILADELPHIA,PA 19107, USA. RI Schnall, Mitchell/D-1149-2009 NR 47 TC 93 Z9 94 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 1994 VL 193 IS 1 BP 49 EP 57 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH229 UT WOS:A1994PH22900015 PM 8090921 ER PT J AU ZERBEY, AL MUELLER, PR DAWSON, SL HOOVER, HC AF ZERBEY, AL MUELLER, PR DAWSON, SL HOOVER, HC TI PLEURAL SEEDING FROM HEPATOCELLULAR-CARCINOMA - A COMPLICATION OF PERCUTANEOUS ALCOHOL ABLATION SO RADIOLOGY LA English DT Article DE ALCOHOL; INTERVENTIONAL PROCEDURES, COMPLICATIONS; LIVER, INTERVENTIONAL PROCEDURE; LIVER NEOPLASMS, METASTASES ID ETHANOL INJECTION THERAPY; HEPATIC-TUMORS AB The authors present a case of proved seeding of the pleural space secondary to alcohol ablation of a primary hepatocellular carcinoma. The patient underwent alcohol ablation for a 6.5-cm-diameter tumor in the right lobe of the liver; approximately 20 needle punctures were required to ensure complete or almost complete destruction of the tumor. Six months after the original ablation, a hypervascular pleural metastasis was noted adjacent to the original lesion at computed tomography. Percutaneous biopsy of the pleural lesion showed hepatocellular carcinoma. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 11 TC 36 Z9 36 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 1994 VL 193 IS 1 BP 81 EP 82 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH229 UT WOS:A1994PH22900020 PM 8090925 ER PT J AU BENACERRAF, BR NADEL, A BROMLEY, B AF BENACERRAF, BR NADEL, A BROMLEY, B TI IDENTIFICATION OF 2ND-TRIMESTER FETUSES WITH AUTOSOMAL TRISOMY BY USE OF A SONOGRAPHIC SCORING INDEX SO RADIOLOGY LA English DT Article DE CHROMOSOMES, ABNORMALITIES; DOWN SYNDROME; FETUS, ABNORMALITIES; FETUS, US ID SERUM ALPHA-FETOPROTEIN; FEMUR LENGTH RATIO; DOWN-SYNDROME; CHROMOSOMAL-ABNORMALITIES; 2ND TRIMESTER; 2ND-TRIMESTER FETUS; FETAL PYELECTASIS; SCREENING TOOL; AMNIOCENTESIS; ASSOCIATION AB PURPOSE: To evaluate the ability to identify fetuses with autosomal trisomy by use of sonographic features in the form of a scoring system. MATERIALS AND METHODS: The presence of nuchal thickening, longbone shortness, pyelectasis, hyperechoic bowel, choroid plexus cyst, and major anatomic defects was prospectively evaluated in 60 trisomic fetuses aged 14-21 weeks and 106 second-trimester control fetuses. RESULTS: Forty-five fetuses had Down syndrome, 13 had trisomy 18, and two had trisomy 13. Based on previous criteria for short femur and humerus, pyelectasis, nuchal thickening, echogenic bowel, and choroid plexus cysts, a scoring system for detection of aneuploidy was developed. it enabled identification of 33 fetuses with Down syndrome (73%), 11 (85%) with trisomy 18, two (100%) with trisomy 13, and four control fetuses with abnormality (4%). The positive predictive value in patients in 1/250, 1/500, and 1/1,000 risk groups was 7.2%, 3.7%, and 1.9% for identification of a fetus with Down syndrome. CONCLUSION: These sonographic markers seem to be sensitive for the detection of chromosomal abnormalities. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA. NR 34 TC 113 Z9 117 U1 0 U2 3 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 1994 VL 193 IS 1 BP 135 EP 140 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PH229 UT WOS:A1994PH22900029 PM 8090881 ER PT J AU ELIAS, AD AYASH, LJ WHEELER, C SCHWARTZ, G TEPLER, I MCCAULEY, M MAZANET, R SCHNIPPER, L FREI, E ANTMAN, KH AF ELIAS, AD AYASH, LJ WHEELER, C SCHWARTZ, G TEPLER, I MCCAULEY, M MAZANET, R SCHNIPPER, L FREI, E ANTMAN, KH TI HIGH-DOSE IFOSFAMIDE/CARBOPLATIN/ETOPOSIDE WITH AUTOLOGOUS HEMATOPOIETIC STEM-CELL SUPPORT - SAFETY AND FUTURE-DIRECTIONS SO SEMINARS IN ONCOLOGY LA English DT Article ID BONE-MARROW SUPPORT; PHASE-I; IFOSFAMIDE; CARBOPLATIN; CANCER; LYMPHOMAS; ETOPOSIDE; CISPLATIN; THERAPY C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA. RP ELIAS, AD (reprint author), HARVARD UNIV,DANA FARBER CANC INST,DIV CLIN ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA13849] NR 13 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 1994 VL 21 IS 5 SU 12 BP 83 EP 85 PG 3 WC Oncology SC Oncology GA PX131 UT WOS:A1994PX13100011 PM 7992072 ER PT J AU HARE, JW AF HARE, JW TI DIABETIC COMPLICATIONS OF DIABETIC PREGNANCIES SO SEMINARS IN PERINATOLOGY LA English DT Review ID RETINOPATHY; MELLITUS; WOMEN; TRANSPLANTATION; NEPHROPATHY; DISEASE; RISK C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP HARE, JW (reprint author), JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 23 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 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD OCT PY 1994 VL 18 IS 5 BP 451 EP 458 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA PN359 UT WOS:A1994PN35900005 PM 7824971 ER PT J AU STAFFORD, RS AF STAFFORD, RS TI STANDARD OF CARE - THE LAW OF AMERICAN BIOETHICS - ANNAS,GJ SO SOCIAL SCIENCE & MEDICINE LA English DT Book Review RP STAFFORD, RS (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD OCT PY 1994 VL 39 IS 7 BP 1007 EP 1008 DI 10.1016/0277-9536(94)90214-3 PG 2 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA PE757 UT WOS:A1994PE75700014 ER PT J AU KENNEDY, EM HARMS, BA STARLING, JR AF KENNEDY, EM HARMS, BA STARLING, JR TI ABSENCE OF MALADAPTIVE NEURONAL PLASTICITY AFTER GENITOFEMORAL-ILIOINGUINAL NEURECTOMY SO SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Central-Surgical-Association CY MAR 03-05, 1994 CL CHICAGO, IL SP CENT SURG ASSOC ID NEURALGIA; PAIN; DIAGNOSIS AB Background. Pain (neuralgia) and paresthesia in the inguinal region after lower abdominal of various medications. The management of chronic pain syndromes is often coordinated by anesthesiologists. Neurolytic therapy is seldom recommended, on the basis of the theory of Methods. Twenty-three patients underwent genitofemoral neurectomy at our institution between 1981 and 1990. Records were reviewed to determine preoperative symptoms, evaluation, and treatment. Patients were contacted and questioned about current symptoms and disability. Results. All records were reviewed. Sixteen (70%) of the patients were located for long-term follow-up. Patients were symptomatic for an average of 3.3 years and underwent 3.1 operations before referral. Inguinal herniorrhaphy was the most common initial surgery (14 of 16 patients). All patients underwent multidisciplinary evaluation. Fifteen underwent L(1-2) paraspinous nerve block, and 13 had total pain relief Postoperative follow-up ranged from 36 to 144 months. Ten patients reported significant pain relief and three patients reported slight improvement. Three of the six patients who had persistent neuralgia had significant orchialgia. None of the patients who had significant relief had preoperative testicular pain. Conclusions. Genitofemoral neurectomy provided long-term relief in 62.5% of patients with genitofemoral neuralgia. Severe testicular pain indicated a less favorable outcome. These data do not support the maladaptive neuronal plasticity theory but do support early referral of some patients for neurectomy. C1 UNIV WISCONSIN HOSP & CLIN,DEPT SURG,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,SURG SERV,MADISON,WI. NR 14 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD OCT PY 1994 VL 116 IS 4 BP 665 EP 671 PG 7 WC Surgery SC Surgery GA PK681 UT WOS:A1994PK68100011 PM 7940164 ER PT J AU SARAC, TP SOUBA, WW MILLER, JNH RYAN, CK KOCH, M BESSEY, PQ SAX, HC AF SARAC, TP SOUBA, WW MILLER, JNH RYAN, CK KOCH, M BESSEY, PQ SAX, HC TI STARVATION INDUCES DIFFERENTIAL SMALL-BOWEL LUMINAL AMINO-ACID-TRANSPORT SO SURGERY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Central-Surgical-Association CY MAR 03-05, 1994 CL CHICAGO, IL SP CENT SURG ASSOC ID TOTAL PARENTERAL-NUTRITION; GLUTAMINE TRANSPORT; ADAPTIVE REGULATION; MEMBRANE-VESICLES; RAT; ARGININE; INJURY; CELLS; GUT AB Background. The importance of small intestinal mucosa functions has been emphasized in recent years gut metabolism becomes better defined. One of the major activities of the enterocyte is amino acid transport, which is important not only for the organism but also for the integrity of the mucosa. Bowel rest during the postoperative period is marked by decreased calorie and protein intake with atrophy of the brush border mucosa. We sought to determine whether active amino acid transport is altered during 72 hours of fasting. Methods. New Zealand white rabbits were fed (control) of fasted for 72 hours. Brush border membrane vesicles were prepared from scraped jejunal mucosa, and their purity was assessed by marker enzyme enrichment (17- to 25-fold). Transport of tritiated glutamine, arginine, alanine, methylamino-isobutyric acid (MeAIB), and leucine into brush border membrane vesicles was measured by rapid mixing filtration. Results. Fasted animals lost on average 138 +/- 51 gm of body weight. Glutamine and arginine transport were decreased in rabbits fasted for 72 hours compared with controls; alanine, MeAIB, and leucine transport were maintained. The decrease in Glutamine transport was due to a decrease in V-max (545 +/- 22 versus 836 +/- 93 pmol/mg/protein/10 sec; p < 0.05), consistent with a decrease in the number of functional transporter proteins. K-m values were similar in both groups (644 +/- 25 versus 624 +/- 18 mu mol/L), indicating no change in carrier affinity. Conclusion. Differential changes occur in brush border amino acid transport during a 3-day period of bowel rest. The apparent gut nutritive transporters for Glutamine and arginine are decreased, although the gluconeogenic transporters for alanine, MeAIB, and leucine are maintained. These adaptive changes may help explain the difficulties seen in postoperative and critically ill patients on prolonged bowel rest. C1 UNIV ROCHESTER,MED CTR,DEPT SURG,ROCHESTER,NY 14642. MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,BOSTON,MA. NR 20 TC 21 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD OCT PY 1994 VL 116 IS 4 BP 679 EP 686 PG 8 WC Surgery SC Surgery GA PK681 UT WOS:A1994PK68100013 PM 7940166 ER PT J AU PFLIEGLER, G ELGAMAL, B BADIMON, JJ BADIMON, L CRAWFORD, N AF PFLIEGLER, G ELGAMAL, B BADIMON, JJ BADIMON, L CRAWFORD, N TI INHIBITION OF PLATELET RECRUITMENT TO ARTERIAL LESIONS BY PREDEPOSITION OF PLATELETS CONTAINING ENCAPSULATED ILOPROST SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID MUSCLE CELL-PROLIFERATION; ANTITHROMBOTIC THERAPY; VESSEL WALL; BLOOD; ANGIOPLASTY; RESTENOSIS; DEPOSITION; DISEASE; THROMBI; INVITRO AB Drugs can be encapsulated within blood platelets by reversible electroporation and can be haemostatically targeted to vessel wall injury sites. Initial studies with iloprost-loaded pig platelets and pig aorta tunica media in perfusion circuits are presented. After autologous reconstitution into blood, no significant difference was observed in the deposition of (111)Indium labelled sham-loaded and untreated platelets onto the tunica media during perfusion under low and high shear conditions. In paired experiments (n = 10 pairs), the deposition of iloprost loaded platelets was significantly lower (mean 61%) after 5 min perfusion than the deposition from blood containing sham-loaded (control) platelets. A similar significant reduction (mean 54%) was seen after 10 min perfusion. Pre-perfusion of iloprost-loaded platelets for 10 min under low shear conditions (212/s), followed by 5 min perfusion of (111)Indium labelled normal platelets, significantly reduced the secondary platelet deposition (p <0.01) when compared with the deposition seen when control untreated platelets were preperfused. Significant differences (p <0.001) in secondary deposition were also observed when primary and secondary platelet perfusions were made under high shear (1690/s). Histology of the tunica media segments post perfusion, supported the inhibitory effect of predeposited iloprost-loaded platelets on secondary platelet recruitment. By exploiting their natural haemostatic propensity, drug-loaded platelets can be targeted to vessel wall injury sites. Appropriate drugs could be packaged that may passivate the carrier platelets at the lesion inhibiting thrombus formation or they may act as a depot for sustained drug release. This platelet drug delivery strategy may have application in the prevention of the thrombotic and restenotic events that can occur post angioplasty, or following therapy with thrombolytics, or after more invasive surgical procedures involving vascular reconstruction or prosthetic implantation. C1 ROYAL FREE HOSP,SCH MED,DEPT BIOCHEM,LONDON NW3 2PF,ENGLAND. MASSACHUSETTS GEN HOSP,CARDIAC RES UNIT,BOSTON,MA. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 22 TC 3 Z9 3 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD OCT PY 1994 VL 72 IS 4 BP 604 EP 610 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA PL563 UT WOS:A1994PL56300021 PM 7533337 ER PT J AU POPOVSKY, MA ANDERSON, K HUME, H PISCIOTTO, P HINES, D AF POPOVSKY, MA ANDERSON, K HUME, H PISCIOTTO, P HINES, D TI TRANSFUSION PRACTICES AMONG HIV-POSITIVE PATIENTS SO TRANSFUSION LA English DT Meeting Abstract C1 AMER RED CROSS, DEDHAM, MA USA. DANA FARBER CANC INST, BOSTON, MA USA. HOP ST JUSTINE, MONTREAL H3T 1C5, PQ, CANADA. UNIV CONNECTICUT, CTR HLTH, FARMINGTON, CT USA. AMER ASSOC BLOOD BANKS, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD OCT PY 1994 VL 34 IS 10 SU S BP S29 EP S29 PG 1 WC Hematology SC Hematology GA PM339 UT WOS:A1994PM33900116 ER PT J AU LAWRENCE, VA BIRCH, S GAFNI, A AF LAWRENCE, VA BIRCH, S GAFNI, A TI IMPACT OF NEW CLINICAL GUIDELINES ON THE NORTH-AMERICAN BLOOD ECONOMY SO TRANSFUSION MEDICINE REVIEWS LA English DT Article ID PHARMACEUTICAL MANUFACTURING APPROACH; TRANSFUSION MEDICINE; CELL TRANSFUSION; UNITED-STATES; COLLECTION; CONTROVERSIES; STRATEGIES; SURGERY; BANKS C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. MCMASTER UNIV,HLTH SCI CTR,CTR HLTH ECON & POLICY ANAL,DEPT CLIN EPIDEMIOL & BIOSTAT,HAMILTON,ON,CANADA. RP LAWRENCE, VA (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 40 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 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD OCT PY 1994 VL 8 IS 4 BP 232 EP 241 DI 10.1016/S0887-7963(94)70115-2 PG 10 WC Hematology SC Hematology GA PL840 UT WOS:A1994PL84000002 PM 7841667 ER PT J AU TOLKOFFRUBIN, NE RUBIN, RH AF TOLKOFFRUBIN, NE RUBIN, RH TI THE INTERACTION OF IMMUNOSUPPRESSION WITH INFECTION IN THE ORGAN TRANSPLANT RECIPIENT SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the American-Society-of-Transplant-Physicians: Symposium on High-Risk Transplantation CY MAY 16-18, 1994 CL CHICAGO, IL ID EPSTEIN-BARR-VIRUS; RENAL-ALLOGRAFT RECIPIENTS; HEPATITIS-C VIRUS; LYMPHOPROLIFERATIVE DISORDER; CYCLOSPORIN-A; ANTIBODY; DISEASE; THERAPY; INVITRO; OKT3 C1 MASSACHUSETTS GEN HOSP,DIALYSIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MIT,DIV HLTH SCI & TECHNOL,CTR EXPTL PHARMACOL & THERAPEUT,CAMBRIDGE,MA 02139. NR 17 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD OCT PY 1994 VL 26 IS 5 SU 1 BP 16 EP 19 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PQ106 UT WOS:A1994PQ10600005 PM 7940970 ER PT J AU SNYDMAN, DR WERNER, BG DOUGHERTY, NN GRIFFITH, J ROHRER, RH FREEMAN, R JENKINS, R LEWIS, WD OROURKE, E FAWAZ, K HOFFMAN, MA KAPLAN, M BAREFOOT, L RUBIN, RH DIENSTAG, JL DORAN, M VACANTI, J HAMMER, S MARTIN, M FAIRCHILD, R GRADY, GF LESZCZYNSKI, J KATZ, A FAUSETT, G AF SNYDMAN, DR WERNER, BG DOUGHERTY, NN GRIFFITH, J ROHRER, RH FREEMAN, R JENKINS, R LEWIS, WD OROURKE, E FAWAZ, K HOFFMAN, MA KAPLAN, M BAREFOOT, L RUBIN, RH DIENSTAG, JL DORAN, M VACANTI, J HAMMER, S MARTIN, M FAIRCHILD, R GRADY, GF LESZCZYNSKI, J KATZ, A FAUSETT, G TI A FURTHER ANALYSIS OF THE USE OF CYTOMEGALOVIRUS IMMUNE GLOBULIN IN ORTHOTOPIC LIVER-TRANSPLANT PATIENTS AT RISK FOR PRIMARY INFECTION SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 13th Annual Meeting of the American-Society-of-Transplant-Physicians: Symposium on High-Risk Transplantation CY MAY 16-18, 1994 CL CHICAGO, IL ID PLACEBO-CONTROLLED TRIAL; VIRUS PNEUMONIA; RECIPIENTS; GANCICLOVIR; DISEASE; PREVENTION; IMMUNOGLOBULIN; COMBINATION; BLOOD C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,DEPT SURG,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,DEPT SURG,BOSTON,MA 02215. CHILDRENS HOSP,DEPT PEDIAT,BOSTON,MA 02115. TUFTS UNIV,SCH MED,MASSACHUSETTS STATE LAB INST,DEPT MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,BOSTON,MA. RP SNYDMAN, DR (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,BOX 238,750 WASHINGTON ST,BOSTON,MA 02111, USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 19 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD OCT PY 1994 VL 26 IS 5 SU 1 BP 23 EP 27 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PQ106 UT WOS:A1994PQ10600007 PM 7940972 ER PT J AU SIEGEL, LM GRINSPOON, SK GARVEY, GJ BILEZIKIAN, JP AF SIEGEL, LM GRINSPOON, SK GARVEY, GJ BILEZIKIAN, JP TI SEPSIS AND ADRENAL-FUNCTION SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID SEPTIC SHOCK; HYPERRENINEMIC HYPOALDOSTERONISM; CRITICAL ILLNESS; HEMORRHAGE; INSUFFICIENCY; ALDOSTERONE; INFECTIONS; ACTH; ILL AB In the setting of sepsis, adrenal function can be difficult to evaluate. Cortisol levels, normally elevated by the stress of sepsis, are occasionally reduced signifying possible adrenal dysfunction. Even elevated cortisol levels do not assure that adrenal reserve is adequate and may in fact portend a preterminal state. Bilateral adrenal hemorrhage leading to adrenal insufficiency is one complication of the sepsis syndrome. This endocrine rounds illustrates the importance in considering adrenal insufficiency and adrenal hemorrhage in patients with overwhelming sepsis while discussing the pathophysiology, clinical presentation, and therapeutic implications of this dire complication. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT PHARMACOL,NEW YORK,NY 10032. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. RP SIEGEL, LM (reprint author), COLUMBIA UNIV,COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032, USA. NR 40 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD OCT PY 1994 VL 5 IS 8 BP 324 EP 328 DI 10.1016/1043-2760(94)90161-9 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PV436 UT WOS:A1994PV43600002 PM 18407225 ER PT J AU SACHS, DH AF SACHS, DH TI THE PIG AS A POTENTIAL XENOGRAFT DONOR SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Review ID NONLETHAL PREPARATIVE REGIMEN; TOLERANCE INDUCTION; TRANSPLANTATION; ALLOGRAFTS AB Miniature swine have several advantages over other potential donor species as a xenograft donor for clinical use. Among these advantages are: (1) unlimited availability; (2) size (similar to human beings); (3) breeding characteristics; (4) physiologic and immunologic similarities to humans. Because of the genetic disparity between these two species, routine immunosuppression will probably not suffice for the long-term survival of pig to primate xenografts. Studies are therefore underway to induce tolerance across this species barrier, utilizing a mixed chimerism approach which has previously been successful for allogeneic and concordant xenogeneic combinations. Hyperacute rejection has been eliminated by an absorption technique and pig kidney xenograft survivals up to 13 days have been achieved. C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. RP SACHS, DH (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH-E,BLDG 149-9019,13TH ST,BOSTON,MA 02129, USA. NR 17 TC 182 Z9 188 U1 2 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD OCT PY 1994 VL 43 IS 1-3 BP 185 EP 191 DI 10.1016/0165-2427(94)90135-X PG 7 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA PP092 UT WOS:A1994PP09200023 PM 7856051 ER PT J AU CENTENO, BA ZIETMAN, AL SHIPLEY, WU SOBCZAK, ML SHIPLEY, JW PREFFER, FI BOYLE, BJ COLVIN, RB AF CENTENO, BA ZIETMAN, AL SHIPLEY, WU SOBCZAK, ML SHIPLEY, JW PREFFER, FI BOYLE, BJ COLVIN, RB TI FLOW CYTOMETRIC ANALYSIS OF DNA-PLOIDY, PERCENT S-PHASE FRACTION, AND TOTAL PROLIFERATIVE FRACTION AS PROGNOSTIC INDICATORS OF LOCAL-CONTROL AND SURVIVAL FOLLOWING RADIATION-THERAPY FOR PROSTATE CARCINOMA SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE PROSTATE CANCER; RADIATION THERAPY; FLOW CYTOMETRY; DNA PLOIDY; S-PHASE FRACTION; TOTAL PROLIFERATIVE FRACTION; LOCAL CONTROL; PROGNOSIS ID DEOXYRIBONUCLEIC-ACID PLOIDY; ADENOCARCINOMA; CANCER; ANTIGEN; RADIOTHERAPY AB Purpose: Treatment recommendations for localized prostate cancer may be improved by the identification of tumor factors prognostic for local control and survival. In this retrospective study, flow cytometric deoxyribonucleic acid (DNA) ploidy analysis and cell cycle analysis were performed on paraffin-embedded biopsy material to determine if additional prognostic factors could be identified in patients treated with radiation therapy. Methods and Materials: Seventy patients with T1-4NxM0 tumors were identified in whom the primary treatment had been radical radiation therapy with no prior or concurrent endocrine therapy and in whom sufficient prostatic tissue was available for flow cytometric analysis. There were 40 diploid, 26 aneuploid, and 4 multiploid cases. Aneuploid and multiploid cases were combined for analysis. Cell cycle data were obtained on all diploid and 10 aneuploid cases. Results: The histologic differentiation of the tumor (well or moderate vs. poor) was an independent predictor of overall survival and disease-free survival (p = 0.05 and 0.01, respectively). Local control was worse in the poorly differentiated patients, although this was not statistically significant in a multivariate analysis (p = 0.08). Neither T-stage, deoxyribonucleic acid ploidy (diploid vs. nondiploid), percent S-phase fraction, nor total proliferative fraction (S-phase fraction + G(2)M) significantly predicted for any of these endpoints. Within the diploid and well or moderately differentiated subgroup (n = 25), S-phase (< 4.2 vs. greater than or equal to 4.2) was a significant predictor of local control (100% vs. 51%, p = 0.03). A comparable distinction could be made using total proliferative fraction (< 10% vs. greater than or equal to 10%) with local control rates of 100% vs. 56% (p = 0.05). Among the poorly differentiated tumors, no similarly favorable subgroup was identified. Conclusions: This retrospective and multivariate analysis identifies both histology and percent S-phase or total proliferative fraction as predictors of local control following irradiation, and confirms that histology, but not DNA ploidy, is significant for overall survival. If these previously unreported findings are confirmed by prospective studies, S-phase should be added to histology as a parameter in the evaluation of clinical trials. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. RP CENTENO, BA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114, USA. NR 22 TC 19 Z9 19 U1 0 U2 3 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 1994 VL 30 IS 2 BP 309 EP 315 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PK072 UT WOS:A1994PK07200007 PM 7928459 ER PT J AU EPP, ER SUIT, HD AF EPP, ER SUIT, HD TI THE NEED FOR ONLINE PORTAL IMAGES OF DIAGNOSTIC-X-RAY QUALITY FROM LINEAR ACCELERATORS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID ENERGY BREMSSTRAHLUNG BEAMS; PATIENT SETUP; RADIOTHERAPY; VERIFICATION; MEGAVOLTAGE; ARRAY RP EPP, ER (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 30 PY 1994 VL 30 IS 2 BP 495 EP 496 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PK072 UT WOS:A1994PK07200031 PM 7928477 ER PT J AU MELDER, RJ JAIN, RK AF MELDER, RJ JAIN, RK TI REDUCTION OF RIGIDITY IN HUMAN ACTIVATED NATURAL-KILLER-CELLS BY THIOGLYCOLATE TREATMENT SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE NATURAL KILLER CELLS; RIGIDITY; IL-2 ID ADOPTIVE IMMUNOTHERAPY; MELANOMA-CELLS; LAK CELLS; INTERLEUKIN-2; GLUTATHIONE; ESTABLISHMENT; MACROPHAGES; LYMPHOCYTES; DETERMINANT; METASTASIS AB Successful delivery of effector cells to tumor vasculature and the expression of cellular activities, such as extravasation and tumor infiltration are important aspects of the immune intervention of neoplastic disease. The structural rigidity of the effector cell, an indication of its cytoskeletal characteristics, plays an important role in influencing cellular functions and hemodynamic behavior as well as systemic distribution. The present study was designed to identify an agent which can modify the viscoelastic properties of human natural killer cells. A reducing compound, thioglycollate (TGA), was found to be an effective agent. Changes in cellular rigidity with respect to dose and duration of treatment with TGA were quantified. Micropipet aspiration was used to measure the resistance of NK cells to an imposed external deformation. Cultures of adherent human NK cells were expanded in interleukin 2 (IL-2) for 14 days, removed from culture and resuspended in medium with IL-2 and selected concentrations of TGA ranging from 0.032 mg/ml to 0.250 mg/ml. At 24 h intervals, the cell samples were removed and tested for their viscoelastic properties. Following 24 h of incubation, only TGA at 0.032 mg/ml produced a significant increase in cellular deformability. At 48 h of incubation, NK cell deformability was twice that obtained at 24 h. Higher concentrations of TGA also produced increased deformability after 48 h of incubation. Following 72 h of incubation, all concentrations of TGA tested produced increased deformability; however, the 0.032 mg/ml concentration produced the highest level of deformability combined with high viability (> 95%) as well as activated cell morphology. This treatment did not significantly alter the cytotoxic activity of these cells against a sensitive tumor target cell. These findings indicate that short term culture with TGA may be used to significantly reduce NK cell rigidity without decreasing cell viability or function. Thus, TGA may be a useful compound for altering the theological properties of activated lymphocytes prior to adoptive transfer. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP MELDER, RJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,TUMOR BIOL STEELE LAB,FRUIT ST,BOSTON,MA 02114, USA. NR 30 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP 30 PY 1994 VL 175 IS 1 BP 69 EP 77 DI 10.1016/0022-1759(94)90332-8 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA PL208 UT WOS:A1994PL20800007 PM 7930640 ER PT J AU MELDER, RJ ELMALEH, D BROWNELL, AL BROWNELL, GL JAIN, RK AF MELDER, RJ ELMALEH, D BROWNELL, AL BROWNELL, GL JAIN, RK TI A METHOD FOR LABELING CELLS FOR POSITRON EMISSION TOMOGRAPHY (PET) STUDIES SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; NATURAL KILLER CELL; LABELING; CYTOTOXICITY ID TUMOR-INFILTRATING LYMPHOCYTES; ACTIVATED KILLER-CELLS; ADOPTIVE IMMUNOTHERAPY; MELANOMA; TRACKING; INVIVO; MICE AB Positron emission tomography (PET) may provide an ideal means of monitoring the delivery of cells to normal and pathological tissue owing to its high resolution, specificity and three dimensional imaging capabilities. In order to implement such a technique, it is important to develop a labeling method for cells which provides a rapid and stable incorporation of the positron emitter without altering the viability or functional activity of the cells to be studied. Two approaches have been explored to achieve this end: metabolic incorporation of 2-[F-18]fluorodeoxyglucose (2-[F-18]FDG) or protein labeling with [C-11]methyl iodide (MI). IL-2 activated mouse natural killer lymphocytes were expanded in culture for 7 days and used for these studies. Uptake of 2-[F-18]FDG by the natural killer cells was found to occur rapidly and to level off after 30 min. The amount of cell-associated label was found to decay at a steady rate immediately following the procedure, with approximately 21% loss of label after 1 h. In contrast, labeling of cells with MI provided a stable association for 60 min which did not alter the viability or the cytotoxic activity of the cells. Injection of the labeled cells into a normal mouse followed by a full body scanning procedure demonstrated the accumulation of the cells in the lungs which corresponded to those seen by microscopy. These findings suggest that labeling lymphocyte populations with MI may provide a rapid and practical means to quantify systemic cell distribution by PET. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP MELDER, RJ (reprint author), HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,FRUIT ST,BOSTON,MA 02114, USA. NR 19 TC 33 Z9 33 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD SEP 30 PY 1994 VL 175 IS 1 BP 79 EP 87 DI 10.1016/0022-1759(94)90333-6 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA PL208 UT WOS:A1994PL20800008 PM 7930641 ER PT J AU TSAI, LH DELALLE, I CAVINESS, VS CHAE, T HARLOW, E AF TSAI, LH DELALLE, I CAVINESS, VS CHAE, T HARLOW, E TI P35 IS A NEURAL-SPECIFIC REGULATORY SUBUNIT OF CYCLIN-DEPENDENT KINASE-5 SO NATURE LA English DT Article ID PROTEIN-KINASE; CELL-CYCLE; BRAIN AB CYCLIN-dependent kinase 5 (Cdk5) was originally isolated through its structural homology to human Cdc2(1), a key regulator of cell-cycle progression(2-6). In tissue samples from adult mice, Cdk5 protein is found at the highest level in brain, at an intermediate level in testis, and at low or undetectable levels in all other tissues, but brain is the only tissue that shows Cdk5 histone H1 kinase activity(7). No equivalent kinase activity has been found in tissue culture cell lines despite high levels of Cdk5 This raised the possibility that a Cdk5 regulatory subunit was responsible for the activation of Cdk5 in brain. Here we describe the cloning and characterization of a regulatory subunit for Cdk5 known as p35. p35 displays a neuronal cell-specific pattern of expression, it associates physically with Cdk5 in vivo and activates the Cdk5 kinase. p35 differs from the mammalian cyclins and thus represents a new type of regulatory subunit for cyclin-dependent kinase activity. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. NR 18 TC 689 Z9 712 U1 1 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 29 PY 1994 VL 371 IS 6496 BP 419 EP 423 DI 10.1038/371419a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ285 UT WOS:A1994PJ28500043 PM 8090221 ER PT J AU GACZYNSKA, M ROCK, KL SPIES, T GOLDBERG, AL AF GACZYNSKA, M ROCK, KL SPIES, T GOLDBERG, AL TI PEPTIDASE ACTIVITIES OF PROTEASOMES ARE DIFFERENTIALLY REGULATED BY THE MAJOR HISTOCOMPATIBILITY COMPLEX-ENCODED GENES FOR LMP2 AND LMP7 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROTEOLYSIS; ANTIGEN PRESENTATION; MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I MOLECULE ID MULTICATALYTIC PROTEINASE COMPLEXES; CLASS-II REGION; MHC-LINKED LMP; ANTIGEN PRESENTATION; YEAST PROTEASOME; LYMPHOCYTE-T; SUBUNITS; PROTEOLYSIS; INTERFERON; EXPRESSION AB Recent studies have implicated proteasomes in the generation of the antigenic peptides that are presented on major histocompatibility complex class I molecules to T lymphocytes. Interferon gamma modifies the subunit composition of proteasomes and causes changes in their peptidase activities that should favor the production of peptides with hydrophobic or basic carboxyl termini (i.e., the types found on major histocompatibility complex class I molecules). It has been proposed that these changes in peptidase activity are due to incorporation into proteasomes of the major histocompatibility complex-encoded subunits LMP2 and -7, which are induced by interferon gamma. Here we show by gene transfection into lymphoblasts or HeLa cells that LMP7 increases the capacity (V-max) of 20S and 26S proteasomes to cleave peptides after hydrophobic and basic residues without affecting hydrolysis after acidic residues. These changes depended on the amount of LMP7 subunits incorporated into proteasomes. Transfection of LMP2 reduced cleavage of peptides after acidic residues, increased hydrolysis after basic residues, and did not affect the hydrophobic activity. Since the activity of the total proteasome population changed after incorporation of only small amounts of LMP2 or -7, these subunits must cause major alterations in peptidase activity. Thus, their expression can account for the changes in proteasome activity induced by interferon gamma, and these findings lend further support to the proposed roles of LMPs in altering the nature of the peptides generated for antigen presentation. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. RP GACZYNSKA, M (reprint author), HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI20248]; NIGMS NIH HHS [GM46147] NR 36 TC 235 Z9 240 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 27 PY 1994 VL 91 IS 20 BP 9213 EP 9217 DI 10.1073/pnas.91.20.9213 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800005 PM 7937744 ER PT J AU GEARING, M REBECK, GW HYMAN, BT TIGGES, J MIRRA, SS AF GEARING, M REBECK, GW HYMAN, BT TIGGES, J MIRRA, SS TI NEUROPATHOLOGY AND APOLIPOPROTEIN-E PROFILE OF AGED CHIMPANZEES - IMPLICATIONS FOR ALZHEIMER-DISEASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AMYLOID; PRIMATE; RHESUS MONKEY; AGING ID AMYLOID PRECURSOR PROTEIN; DENSITY LIPOPROTEIN RECEPTOR; PAIRED HELICAL FILAMENTS; E MESSENGER-RNA; SENILE PLAQUES; BETA-PROTEIN; TAU TAU; NEUROFIBRILLARY TANGLES; NONHUMAN-PRIMATES; SQUIRREL-MONKEYS AB Neuropathological findings in three aged chimpanzees were compared with those in rhesus monkeys and individuals with Alzheimer disease. Senile plaques and blood vessels were immunoreactive for amyloid beta-protein and apolipoprotein E (apoE) in the nonhuman primates, recapitulating findings in human aging and Alzheimer disease. Neurofibrillary tangles, another hallmark of Alzheimer disease, were absent. PCR/restriction-enzyme analysis in chimpanzees revealed an APOE profile similar to the human APOE type 4 allele associated with an increased risk of Alzheimer disease. These findings militate against the hypothesis that the absence of APOE type 3 allele predisposes to neurofibrillary tangle formation and support the value of aged primates for exploring mechanisms of amyloid processing and the role of apoE. C1 VET AFFAIRS MED CTR,DEPT LAB MED & PATHOL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,BOSTON,MA 02114. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. FU NIA NIH HHS [AG00001, AG05598, AG10130] NR 78 TC 110 Z9 110 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 27 PY 1994 VL 91 IS 20 BP 9382 EP 9386 DI 10.1073/pnas.91.20.9382 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800039 PM 7937774 ER PT J AU BISSLER, JJ CICARDI, M DONALDSON, VH GATENBY, PA ROSEN, FS SHEFFER, AL DAVIS, AE AF BISSLER, JJ CICARDI, M DONALDSON, VH GATENBY, PA ROSEN, FS SHEFFER, AL DAVIS, AE TI A CLUSTER OF MUTATIONS WITHIN A SHORT TRIPLET REPEAT IN THE C1 INHIBITOR GENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SLIPPED MISPAIRING; DNA DELETION; DNA DUPLICATION ID UNUSUAL DNA STRUCTURES; DISEASE AB Mutations in the C1 inhibitor gene that result in low functional levels of C1 inhibitor protein cause hereditary angioneurotic edema. This disease is characterized by episodic edema leading to considerable morbidity and death. Among 60 unreported kindred with the disease, four patients were discovered to have mutations clustered within a 12-bp segment of exon 5 from nucleotide 8449 to nucleotide 8460. This short segment of DNA contains three direct repeats of the triplet CAA and is immediately preceded by a similar adenosine-rich sequence (CAAGAACAC). These triplet repeats make this region susceptible to mutation by a slipped mispairing mechanism. There are two other short triplet repeat elements in the coding region for this gene, but they have not become mutated in any kindred examined. This suggests that the apparent enhanced mutation rate in this region of exon 5 may be influenced by DNA structural characteristics. C1 UNIV CINCINNATI,CHILDRENS HOSP RED FDN,DEPT MED,CINCINNATI,OH 45229. CLIN MED,I-20122 MILAN,ITALY. ROYAL PRINCE ALFRED HOSP,DEPT CLIN IMMUNOL,CAMPERDOWN,NSW 2050,AUSTRALIA. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. RP BISSLER, JJ (reprint author), UNIV CINCINNATI,CHILDRENS HOSP RES FDN 5,DEPT PEDIAT,3333 BURNET AVE,CINCINNATI,OH 45229, USA. RI cicardi, marco/K-9219-2016 OI cicardi, marco/0000-0003-1251-225X FU NICHD NIH HHS [HD22082] NR 20 TC 20 Z9 20 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 27 PY 1994 VL 91 IS 20 BP 9622 EP 9625 DI 10.1073/pnas.91.20.9622 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PJ428 UT WOS:A1994PJ42800088 PM 7937817 ER PT J AU BLOCH, SD BILLINGS, JA AF BLOCH, SD BILLINGS, JA TI PATIENT REQUESTS TO HASTEN DEATH - EVALUATION AND MANAGEMENT IN TERMINAL CARE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PHYSICIAN-ASSISTED SUICIDE; CANCER PAIN; PSYCHOLOGICAL FUNCTION; DEPRESSIVE-DISORDERS; MEDICAL INPATIENTS; MENTAL-DISORDERS; HOPELESSLY ILL; AIDS; EUTHANASIA; SYMPTOMS AB Terminally ill patients often hope that death will come quickly. They may broach this wish with their physicians, and even request assistance in hastening death. Thoughts about accelerating death usually do not reflect a sustained desire for suicide or euthanasia, but have other important meanings that require exploration. When patients ask for death to be hastened, the following areas should be explored: the adequacy of symptom control; difficulties in the patient's relationships with family, friends, and health workers; psychological disturbances, especially grief, depression, anxiety, organic mental disorders, and personality disorders; and the patient's personal orientation to the meaning of life and suffering. Appreciation of the clinical determinants and meanings of requests to hasten death can broaden therapeutic options. In all cases, patient requests for accelerated death require ongoing discussion and active efforts to palliate physical and psychological distress. In those infrequent instances when a patient with persistent, irremediable suffering seeks a prompt and comfortable death, the physician must confront the moral, legal, and professional ramifications of his or her response. Rarely, acceding to the patient's request for hastening death may be the least terrible therapeutic alternative. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT AMBULATORY CARE & PREVENT,TEACHING PROGRAM,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHELSEA MEM HLTH CTR,DEPT MED,ADULT MED UNIT,BOSTON,MA 02114. TRINITY HOSPICE GREATER BOSTON,DEPT MED,BOSTON,MA. OLSTEN KIMBERLY QUAL CARE HOSPICE,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. NR 79 TC 96 Z9 96 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 26 PY 1994 VL 154 IS 18 BP 2039 EP 2047 DI 10.1001/archinte.154.18.2039 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA PH653 UT WOS:A1994PH65300003 PM 7522432 ER PT J AU CUNNINGHAM, LA SHORT, MP BREAKEFIELD, XO BOHN, MC AF CUNNINGHAM, LA SHORT, MP BREAKEFIELD, XO BOHN, MC TI NERVE GROWTH-FACTOR RELEASED BY TRANSGENIC ASTROCYTES ENHANCES THE FUNCTION OF ADRENAL CHROMAFFIN CELL GRAFTS IN A RAT MODEL OF PARKINSONS-DISEASE SO BRAIN RESEARCH LA English DT Article DE NERVE GROWTH FACTOR; TRANSGENIC ASTROCYTE; ADRENAL CHROMAFFIN CELL; TRANSPLANTATION; PARKINSONS DISEASE ID GENETICALLY MODIFIED CELLS; CONTROLLED ONCOGENE EXPRESSION; TRANSFORMED MOUSE FIBROBLASTS; FACTOR SYNTHESIS SECRETION; FACTOR NGF SYNTHESIS; GENE-TRANSFER; MEDULLA GRAFTS; MESSENGER-RNA; BEHAVIORAL RECOVERY; CULTURED ASTROCYTES AB Previous studies have demonstrated that astrocytes genetically modified to express recombinant nerve growth factor (NGF) support the survival and neuronal transdifferentiation of intrastriatal adrenal chromaffin cell grafts at 2 weeks post-transplantation [15]. The present study was performed to determine whether these effects would be maintained at longer limes post-transplantation and, if so, whether the co-grafts would reduce rotational behavior in the unilateral 6-hydroxydopamine-lesioned rat. In the present study, we have demonstrated that primary type I rat astrocytes infected with a replication-defective retrovirus conferring expression of a mouse beta-NGF cDNA sequence secrete NGF at a rate that is approximately 40-fold higher than that of controls (i.e., 8.0 vs. 0.2 pg NGF/h/10(5) cells, respectively). The genetically modified astrocytes were also found to express recombinant NGF following intrastriatal transplantation, as indicated by a 23% increase in striatal NGF content compared with controls, measured at 4 weeks post-transplantation. When NGF-producing astrocytes and adrenal chromaffin cells were co-grafted into the dopamine-denervated striatum of the unilateral 6-hydroxydopamine-lesioned rat, the chromaffin cells displayed extensive neurite outgrowth and a 5-12-fold increase in survival compared to controls at 10 weeks post-grafting. These effects were paralleled by a 60% reduction of apomorphine-induced rotational behavior, suggesting a partial normalization of striatal function. These results suggest that genetically modified astrocytes promote the prolonged survival and function of adrenal chromaffin cell grafts in a rat model of Parkinson's disease. C1 UNIV ROCHESTER,SCH MED,DEPT NEUROBIOL & ANAT,ROCHESTER,NY 14642. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NINDS NIH HHS [NS08906, NS24279, R29 NS32562] NR 78 TC 45 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 26 PY 1994 VL 658 IS 1-2 BP 219 EP 231 PG 13 WC Neurosciences SC Neurosciences & Neurology GA PH002 UT WOS:A1994PH00200028 PM 7834345 ER PT J AU SOGAARD, M TANI, K YE, RR GEROMANOS, S TEMPST, P KIRCHHAUSEN, T ROTHMAN, JE SOLLNER, T AF SOGAARD, M TANI, K YE, RR GEROMANOS, S TEMPST, P KIRCHHAUSEN, T ROTHMAN, JE SOLLNER, T TI A RAB PROTEIN IS REQUIRED FOR THE ASSEMBLY OF SNARE COMPLEXES IN THE DOCKING OF TRANSPORT VESICLES SO CELL LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; BINDING YPT1 PROTEIN; VESICULAR TRANSPORT; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; GOLGI-COMPLEX; SYNAPTIC VESICLES; NEUROTRANSMITTER RELEASE; SACCHAROMYCES-CEREVISIAE; FUSION PROTEIN AB Rab proteins are generally required for transport vesicle docking. We have exploited yeast secretion mutants to demonstrate that a rab protein is required for v-SNAREs and t-SNAREs to assemble. The absence of the rab protein in the docking complex suggests that, in a broad sense, rab proteins participate in a reaction catalyzing SNARE complex assembly. In so doing, mb proteins could help impart an additional layer of specificity to vesicle docking. This mechanism likely involves the Sec1 homolog Sly1, which we identified in isolated docking complexes. We also report the identification of a novel v-SNARE (Ykt6p) component of the yeast ER-Golgi docking complex that has a CAAX box and is predicted to be lipid anchored. The surprising finding that docking complexes can contain many distinct species of SNAREs (Sed5p, Bos1p, Sec22p, Ykt6p, and likely Bet1p, p28, and p14) suggests that multimeric interactions are features of the fusion machinery, and may also improve the fidelity of vesicle targeting. C1 MEM SLOAN KETTERING CANC CTR,PROGRAM MOLEC BIOL,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP SOGAARD, M (reprint author), MEM SLOAN KETTERING CANC CTR,CELLULAR BIOCHEM & BIOPHYS PROGRAM,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [5 P30 CA08748-29] NR 62 TC 436 Z9 439 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 23 PY 1994 VL 78 IS 6 BP 937 EP 948 DI 10.1016/0092-8674(94)90270-4 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PJ294 UT WOS:A1994PJ29400006 PM 7923363 ER PT J AU HASTBACKA, J DELACHAPELLE, A MAHTANI, MM CLINES, G REEVEDALY, MP DALY, M HAMILTON, BA KUSUMI, K TRIVEDI, B WEAVER, A COLOMA, A LOVETT, M BUCKLER, A KAITILA, I LANDER, ES AF HASTBACKA, J DELACHAPELLE, A MAHTANI, MM CLINES, G REEVEDALY, MP DALY, M HAMILTON, BA KUSUMI, K TRIVEDI, B WEAVER, A COLOMA, A LOVETT, M BUCKLER, A KAITILA, I LANDER, ES TI THE DIASTROPHIC DYSPLASIA GENE ENCODES A NOVEL SULFATE TRANSPORTER - POSITIONAL CLONING BY FINE-STRUCTURE LINKAGE DISEQUILIBRIUM MAPPING SO CELL LA English DT Article ID 3'-PHOSPHOADENOSINE 5'-PHOSPHOSULFATE SYNTHESIS; INTACT ARTICULAR-CARTILAGE; BORDER MEMBRANE-VESICLES; CYSTIC-FIBROSIS GENE; BRACHYMORPHIC MICE; INORGANIC SULFATE; NUCLEOTIDE-SEQUENCE; HAPLOTYPE ANALYSIS; HEPARAN-SULFATE; RAT INVIVO AB Diastrophic dysplasia (DTD) is a well-characterized autosomal recessive osteochondrodysplasia with clinical features including dwarfism, spinal deformation, and specific joint abnormalities. The disease occurs in most populations, but is particularly prevalent in Finland owing to an apparent founder effect. DTD maps to distal chromosome 5q and, based on linkage disequilibrium studies in the Finnish population, we had previously predicted that the DTD gene should lie about 64 kb away from the CSF1R locus. Here, we report the positional cloning of the DTD gene by finestructure linkage disequilibrium mapping. The gene lies in the predicted location, approximately 70 kb proximal to CSF1R, and encodes a novel sulfate transporter. Impaired function of its product is likely to lead to undersulfation of proteoglycans in cartilage matrix and thereby to cause the clinical phenotype of the disease. These results demonstrate the power of linkage disequilibrium mapping in isolated populations for positional cloning. C1 UNIV HELSINKI,DEPT MED GENET,SF-00014 HELSINKI,FINLAND. FOLKHALSAN INST GENET,SF-00014 HELSINKI,FINLAND. UNIV TEXAS,SW MED CTR,DEPT BIOCHEM,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,MCDERMOTT CTR,DALLAS,TX 75235. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT NEUROGENET,BOSTON,MA 02129. UNIV HELSINKI,CENT HOSP,DEPT MED GENET,SF-00290 HELSINKI,FINLAND. RP HASTBACKA, J (reprint author), WHITEHEAD INST BIOMED RES,9 CAMBRIDGE CTR,CAMBRIDGE,MA 02142, USA. RI Kusumi, Kenro/J-2626-2012 OI Kusumi, Kenro/0000-0002-1458-4540 FU NHGRI NIH HHS [HG00098, HG00882]; NIAMS NIH HHS [AR41970] NR 83 TC 554 Z9 564 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 23 PY 1994 VL 78 IS 6 BP 1073 EP 1087 DI 10.1016/0092-8674(94)90281-X PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PJ294 UT WOS:A1994PJ29400017 PM 7923357 ER PT J AU MINDRINOS, M KATAGIRI, F YU, GL AUSUBEL, FM AF MINDRINOS, M KATAGIRI, F YU, GL AUSUBEL, FM TI THE A-THALIANA DISEASE RESISTANCE GENE RPS2 ENCODES A PROTEIN CONTAINING A NUCLEOTIDE-BINDING SITE AND LEUCINE-RICH REPEATS SO CELL LA English DT Article ID MEMBRANE-SPANNING PROTEINS; MOLECULAR-CLONING; ADENYLATE-CYCLASE; ARABIDOPSIS; IDENTIFICATION; AVIRULENCE; RECOGNITION; SUPPRESSION; EXPRESSION; MUTATIONS AB In plants, resistance to a pathogen is frequently correlated with a genetically defined interaction between a plant resistance gene and a corresponding pathogen avirulence gene. A simple model explains these gene-for-gene interactions: avirulence gene products generate signals (ligands), and resistance genes encode cognate receptors. The A. thaliana RPS2 gene confers resistance to the bacterial pathogen P. syringae carrying the avirulence gene avrRpt2. A map-based positional cloning strategy was used to identify RPS2. The identification of RPS2 was verified using a newly developed transient assay for RPS2 function and by genetic complementation in transgenic plants. RPS2 encodes a novel 105 kDa protein containing a leucine zipper, a nucleotide-binding site, and 14 imperfect leucine-rich repeats. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP MINDRINOS, M (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [GM48707] NR 45 TC 514 Z9 554 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 23 PY 1994 VL 78 IS 6 BP 1089 EP 1099 DI 10.1016/0092-8674(94)90282-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PJ294 UT WOS:A1994PJ29400018 PM 7923358 ER PT J AU XU, XM BARRY, DC SETTLEMAN, J SCHWARTZ, MA BOKOCH, GM AF XU, XM BARRY, DC SETTLEMAN, J SCHWARTZ, MA BOKOCH, GM TI DIFFERING STRUCTURAL REQUIREMENTS FOR GTPASE-ACTIVATING PROTEIN RESPONSIVENESS AND NADPH OXIDASE ACTIVATION BY RAC SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-RESIDUES; BINDING PROTEIN; GAP; IDENTIFICATION; EFFECTOR; RHO; P21; DOMAIN; COMPONENTS; P21RAC1 AB The Rac GTP-binding proteins regulate the actin cytoskeleton and the superoxide-forming NADPH oxidase of phagocytic leukocytes. These functions of Rac are determined by the GTP/GDP state of the protein, which can be modulated by GTPase-activating proteins (GAPs). The interaction of Ras with both downstream signaling targets and GAPs is mediated via an ''effector'' domain (amino acids 3(9-40). We demonstrate that the effector domain of Rac2 is required for both NADPH oxidase activation and actin assembly, but that mutations in this region do not decrease the responsiveness of Rac to GAPs. In contrast, mutations of residues 12 (Gly --> Val) or 61 (Gln --> Leu) inhibit both intrinsic- and GAP-stimulated GTP hydrolysis by Rac2. A double mutation in which both the effector domain and Q61L were modified restored NADPH oxidase activation and membrane ruffling, while the equivalent effector domain and G12V double mutation did not. The Rac2 Q61L mutant had an increased ''affinity'' for NADPH oxidase activation and for GAP binding as compared to the wild type or G12V proteins. These experiments suggest that Rac contains at least two ''effector'' interaction sites, and that changes in binding interactions at one of these sites may influence the function of the other. C1 Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. Scripps Res Inst, DEPT CELL BIOL, LA JOLLA, CA 92037 USA. Scripps Res Inst, DEPT VASC BIOL, LA JOLLA, CA 92037 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, CTR CANC, BOSTON, MA 02129 USA. OI xu, xuemin/0000-0002-7426-272X FU NHLBI NIH HHS [HL48008]; NIGMS NIH HHS [GM44428] NR 36 TC 81 Z9 80 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 23 PY 1994 VL 269 IS 38 BP 23569 EP 23574 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ345 UT WOS:A1994PQ34500030 PM 8089125 ER PT J AU SERRAPAGES, C SAITO, H STREULI, M AF SERRAPAGES, C SAITO, H STREULI, M TI MUTATIONAL ANALYSIS OF PROPROTEIN PROCESSING, SUBUNIT ASSOCIATION, AND SHEDDING OF THE LAR TRANSMEMBRANE PROTEIN-TYROSINE-PHOSPHATASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; CONSTITUTIVE SECRETORY PATHWAY; HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR RECEPTORS; CENTRAL-NERVOUS-SYSTEM; CLEAVAGE SITE; PHOSPHOTYROSINE PHOSPHATASE; IMMUNOGLOBULIN SUPERFAMILY; SEQUENCE REQUIREMENTS; PROTEOLYTIC CLEAVAGE AB The LAR transmembrane protein tyrosine phosphatase (PTPase) is expressed on the cell surface as a complex of two noncovalently associated subunits derived from a proprotein. The 150-kDa E-subunit contains most of the extracellular region, including the immunoglobulin-like and fibronectin type-III-like domains, whereas the 85-kDa P-subunit contains a short ectodomain, the transmembrane peptide, and the two intracellular PTPase domains. The LAR extracellular region is released from the cell surface, suggesting that shedding may be a mechanism to regulate LAR PTPase function. Functional regions necessary for LAR proprotein processing, subunit association, and shedding were determined by analyzing the effect of amino acid substitutions of residues surrounding the cleavage site and scanning the P-subunit ectodomain. Three amino acid residues were identified, two within a penta-arginine sequence and one C-terminal to the cleavage site, that are essential for efficient LAR proprotein cleavage. Several noncontiguous amino acid residues were also identified that play an essential role in LAR subunit association. LAR shedding is shown to be a consequence of proteolytic cleavage at a second site within the P-subunit ectodomain near the transmembrane peptide. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP SERRAPAGES, C (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA55547] NR 77 TC 63 Z9 64 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 23 PY 1994 VL 269 IS 38 BP 23632 EP 23641 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ345 UT WOS:A1994PQ34500039 PM 8089133 ER PT J AU ZHOU, Y LUAN, P LIU, LA SUN, ZP AF ZHOU, Y LUAN, P LIU, LA SUN, ZP TI CHIRAL DERIVATIZING REAGENTS FOR DRUG ENANTIOMERS BEARING HYDROXYL-GROUPS SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Review ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ABSOLUTE-CONFIGURATION; OPTICAL ISOMERS; STEREOSELECTIVE METABOLISM; DILTIAZEM HYDROCHLORIDE; DIOL EPOXIDES; HUMAN-PLASMA; RESOLUTION; WARFARIN; ACID AB This review extensively summarizes and critically evaluates the recent research on the indirect resolution technique for enantiomeric alcohols. Twenty-one chiral derivatizing reagents divided in seven types, including chiral acids, activated acids, chloroformates, isocyanates, carbonyl nitriles, oxazolidin-2-ones and lactones, are described. The derivatization methods of the various chiral reagents, the liquid chromatography separation systems, the detection systems used for the diastereomeric derivatives of alcohols as well as their limitations and the prospects of the indirect resolution technique for the future are thoroughly discussed. This paper aims to instruct the application of a particular chiral reagent and the technical approach to be used and should be beneficial to the development of an indirect resolution method for enantiomeric alcohols as well as to the biomedical investigation of the differences between the antipodes of chiral alcohols. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. NATL INST CONTROL PHARMACEUT & BIOL PROD,BEIJING 100050,PEOPLES R CHINA. RP ZHOU, Y (reprint author), UNIV CALIF SAN FRANCISCO,SCH PHARM,DEPT PHARM,BOX 0446,SAN FRANCISCO,CA 94143, USA. NR 54 TC 19 Z9 20 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD SEP 23 PY 1994 VL 659 IS 1-2 BP 109 EP 126 DI 10.1016/0378-4347(94)00146-4 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA PK357 UT WOS:A1994PK35700006 PM 7820272 ER PT J AU HUANG, ZH HUANG, PL PANAHIAN, N DALKARA, T FISHMAN, MC MOSKOWITZ, MA AF HUANG, ZH HUANG, PL PANAHIAN, N DALKARA, T FISHMAN, MC MOSKOWITZ, MA TI EFFECTS OF CEREBRAL-ISCHEMIA IN MICE DEFICIENT IN NEURONAL NITRIC-OXIDE SYNTHASE SO SCIENCE LA English DT Article ID L-ARGININE; GUANYLATE-CYCLASE; ARTERY OCCLUSION; BRAIN; STIMULATION; MECHANISMS AB The proposal that nitric oxide (NO) or its reactant products mediate toxicity in brain remains controversial in part because of the use of nonselective agents that block NO formation in neuronal, glial, and vascular compartments. In mutant mice deficient in neuronal NO synthase (NOS) activity, infarct volumes decreased significantly 24 and 72 hours after middle cerebral artery occlusion, and the neurological deficits were less than those in normal mice. This result could not be accounted for by differences in blood flow or vascular anatomy. However, infarct size in the mutant became larger after endothelial NOS inhibition by nitro-L-arginine administration. Hence, neuronal NO production appears to exacerbate acute ischemic injury, whereas vascular NO protects after middle cerebral artery occlusion. The data emphasize the importance of developing selective inhibitors of the neuronal isoform. C1 MASSACHUSETTS GEN HOSP,STROKE RES LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,NEUROSURG SERV,BOSTON,MA 02139. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIOVASC RES CTR,DEPT MED,BOSTON,MA 02129. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828, NS2636] NR 33 TC 1294 Z9 1344 U1 1 U2 18 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 23 PY 1994 VL 265 IS 5180 BP 1883 EP 1885 DI 10.1126/science.7522345 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PH258 UT WOS:A1994PH25800038 PM 7522345 ER PT J AU SAGER, R AF SAGER, R TI FUNCTION OF MASPIN - REPLY SO SCIENCE LA English DT Article RP SAGER, R (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 23 PY 1994 VL 265 IS 5180 BP 1894 EP 1894 DI 10.1126/science.265.5180.1894 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PH258 UT WOS:A1994PH25800044 PM 17797228 ER PT J AU FERRIS, T AF FERRIS, T TI INFORMED CONSENT, CANCER, AND TRUTH IN PROGNOSIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP FERRIS, T (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 22 PY 1994 VL 331 IS 12 BP 811 EP 811 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PG301 UT WOS:A1994PG30100021 PM 8065421 ER PT J AU BURTON, MD AF BURTON, MD TI CASE-18-1994 - TUBEROUS SCLEROSIS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID RENAL-CELL CARCINOMA; ANGIOMYOLIPOMA RP BURTON, MD (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 22 PY 1994 VL 331 IS 12 BP 814 EP 814 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PG301 UT WOS:A1994PG30100029 ER PT J AU SIMONIAN, NA ELVHAGE, T CZERNIK, AJ GREENGARD, P HYMAN, BT AF SIMONIAN, NA ELVHAGE, T CZERNIK, AJ GREENGARD, P HYMAN, BT TI CALCIUM/CALMODULIN-DEPENDENT PROTEIN-KINASE-II IMMUNOSTAINING IS PRESERVED IN ALZHEIMERS-DISEASE HIPPOCAMPAL-NEURONS SO BRAIN RESEARCH LA English DT Article DE CALCIUM/CALMODULIN-DEPENDENT PROTEIN KINASE II; PROTEIN PHOSPHORYLATION; ALZHEIMERS DISEASE; PROTEIN KINASE; TAU ID NEUROFIBRILLARY TANGLES; MONOCULAR DEPRIVATION; INSITU HYBRIDIZATION; CEREBRAL-ISCHEMIA; GERBIL BRAIN; C ISOZYMES; RAT-BRAIN; PHOSPHORYLATION; IMMUNOREACTIVITY; TAU AB Alterations in protein phosphorylation may be important in the pathogenesis of Alzheimer's disease and recent observations suggest that a subset of protein kinase pathways may be selectively altered. Calcium/calmodulin-dependent protein kinase II (CaM kinase II) is the most abundant protein kinase in the brain and is believed to play an important role in the regulation of synaptic transmission, long-term potentiation and other forms of neuronal plasticity. We have now evaluated brains of individuals with Alzheimer's disease for changes in the distribution and density of immunoreactivity for the alpha subunit of CaM kinase II. CaM kinase II immunoreactivity was found in cytoarchitectural areas and neurons vulnerable to the formation of neurofibrillary tangles and senile plaques. Over 80% of neurons bearing neurofibrillary tangles expressed CaM kinase II. Loss of CaM kinase II immunoreactivity was found in CA1, commensurate with neuronal loss in this area. Remaining CA1 neurons, however, had preserved CaM kinase II immunoreactivity. Preservation in the distribution and density of CaM kinase II immunoreactivity was observed in other hippocampal regions and in a multimodal association area, area 20. These results suggest CaM kinase II expression in the Alzheimer's disease brain is unaltered despite marked neuropathological changes. C1 ROCKEFELLER UNIV,MOLEC & CELLULAR NEUROSCI LAB,NEW YORK,NY 10021. RP SIMONIAN, NA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,FRUIT ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG 08487, AG 09464, P050-AG 05134] NR 44 TC 22 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 19 PY 1994 VL 657 IS 1-2 BP 294 EP 299 DI 10.1016/0006-8993(94)90979-2 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PG393 UT WOS:A1994PG39300034 PM 7820630 ER PT J AU ODA, T HEANEY, C HAGOPIAN, JR OKUDA, K GRIFFIN, JD DRUKER, BJ AF ODA, T HEANEY, C HAGOPIAN, JR OKUDA, K GRIFFIN, JD DRUKER, BJ TI CRKL IS THE MAJOR TYROSINE-PHOSPHORYLATED PROTEIN IN NEUTROPHILS FROM PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID P210 BCR-ABL; PHILADELPHIA-CHROMOSOME; CELL-LINE; ONCOGENE; GENE; TRANSFORMATION; PRODUCT AB The Philadelphia chromosome (Ph(1)), detected in virtually all cases of chronic myelogenous leukemia (CML), is formed by a reciprocal translocation between chromosome 9 and 22 that fuses Bcr-encoded sequences upstream of exon 2 of c-Abl. This oncogene produces a fusion protein, p210(bcr-abl), in which the Abl tyrosine kinase activity is elevated. Using anti-phosphotyrosine immunoblotting, we have compared the pattern of phosphotyrosine-containing proteins from freshly prepared neutrophils of patients in the stable phase of CML to normal controls. The only consistent difference was the presence of a 39-kDa tyrosine-phosphorylated protein in 18 out of 18 neutrophil samples from CML patients that was not seen in normal controls. This same protein, as assessed by two-dimensional anti-phosphotyrosine immunoblotting, was also present in cell lines expressing p210(bcr-abl), including K562 cells. Using K562 cells as a source of protein, the 39-kDa protein was purified and identified by microsequencing as CrkI, an SH2/SH3 adaptor protein related to the crk oncogene of the avian sarcoma virus, CT10. A direct interaction between CrkI and Abl has also been shown using a yeast two-hybrid screen. C1 OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA 01422, CA 34183, CA 36167] NR 30 TC 233 Z9 238 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 16 PY 1994 VL 269 IS 37 BP 22925 EP 22928 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ164 UT WOS:A1994PQ16400004 PM 8083188 ER PT J AU KUZNETSOV, G CHEN, LB NIGAM, SK AF KUZNETSOV, G CHEN, LB NIGAM, SK TI SEVERAL ENDOPLASMIC-RETICULUM STRESS PROTEINS, INCLUDING ERP72, INTERACT WITH THYROGLOBULIN DURING ITS MATURATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DISULFIDE ISOMERASE; BINDING-PROTEINS; CELLS; RAT; BIP; CALCIUM; AGGREGATION; EXPRESSION; GLUCOSE; OCCURS AB We have previously demonstrated that several endoplasmic reticulum (ER) proteins, including BiP, ERp72, grp94, and protein disulfide isomerase, bind to a denatured thyroglobulin (Tg) affinity column and can be specifically eluted by ATP (Nigam, S. K., Goldberg, A. L., Ho, S., Rohde, M. F., Bush, K. T., and Sherman, M. Y. (1994) J. Biol. Chem. 269, 1744-1749). Using chemical cross linking, we now demonstrate that BiP, ERp72, and grp94 associate with Tg in two types of cultured thyroid cells, FRTL-5 and PCCl3. Whereas BiP could be coimmunoprecipitated with anti-Tg antibodies in the absence of crosslinking, only trace amounts of ERp72 and grp94 were coimmunoprecipitated. Likewise, in both cell types, anti BiP antibodies were able to coimmunoprecipitate Tg in the absence of cross-linking, though ERp72 and grp94 were only minimally present. Coprecipitation of BiP and Tg was abolished when ATP and Mg2+ were added to cell lysates. In contrast, after cross-linking, there was a large increase in the amount of ERp72 and grp94 that coimmunoprecipitated with anti-Tg antibodies, although there was only a slight increase in BiP. Similarly, in cross-linked lysates, grp94 and ERp72 were also coimmunoprecipitated with anti-BiP antibodies. An apparently novel 200-kDa protein was also consistently immunoprecipitated by anti-BiP antibodies in both cell types. In addition, anti-ERp72 antibodies coimmunoprecipitated Tg, BiP, and grp94 only after cross-linking. Analysis of uncross-linked and cross-linked samples by sucrose density gradient centrifugation confirmed that Tg, BiP, grp94, and ERp72 are present together in high molecular weight complexes only after treatment of cells with cross linking reagent. These results suggest that ERp72, as well as BiP and grp94, function as molecular chaperones in the maturation of Tg, potentially as part of a macromolecular complex. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. FU NIGMS NIH HHS [GM38318-07] NR 28 TC 85 Z9 86 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 16 PY 1994 VL 269 IS 37 BP 22990 EP 22995 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ164 UT WOS:A1994PQ16400016 PM 7916014 ER PT J AU SMITH, S DAMORE, PA DREYER, EB AF SMITH, S DAMORE, PA DREYER, EB TI COMPARATIVE TOXICITY OF MITOMYCIN-C AND AND 5-FLUOROURACIL IN-VITRO SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID GLAUCOMA FILTERING SURGERY; POSTOPERATIVE 5-FLUOROURACIL; TRABECULECTOMY; FIBROBLASTS; SUBCONJUNCTIVAL; PROLIFERATION AB The adjunctive use of antimetabolites has revolutionized surgical procedures to correct glaucoma in the past decade. Although much is known about the in vitro and in vivo actions of 5-fluorouracil and mitomycin C, their use in the eye has raised new questions about cellular toxicity. For example, filtering blebs after a surgical procedure supplemented with mitomycin C are relatively avascular in comparison with those seen with 5-fluorouracil supplementation. We investigated the effect of 5-fluorouracil and mitomycin C on cultured capillary endothelial cells and fibroblasts. The viability and morphologic characteristics of 3T3 fibroblasts and capillary endothelial cells were studied in light of increasing doses of 5-fluorouracil and mitomycin. Both cell types showed similar sensitivity to mitomycin C. However fibroblasts were far more sensitive to 5-fluorouracil than were the cultured microvascular endothelial cells. Thus 5-fluorouracil appears to be toxic to fibroblasts while sparing vascular endothelial cells, whereas mitomycin C is cytotoxic for both cell types. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,GLAUCOMA CONSULTAT SERV,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,SURG RES LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG & PATHOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. FU NEI NIH HHS [EY-05985, R01-EY10009]; NINDS NIH HHS [K08-NS01395] NR 24 TC 73 Z9 73 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 15 PY 1994 VL 118 IS 3 BP 332 EP 337 PG 6 WC Ophthalmology SC Ophthalmology GA PF313 UT WOS:A1994PF31300007 PM 8085590 ER PT J AU FISHER, MJ PRCHAL, JF PRCHAL, JT DANDREA, AD AF FISHER, MJ PRCHAL, JF PRCHAL, JT DANDREA, AD TI ANTIERYTHROPOIETIN (EPO) RECEPTOR MONOCLONAL-ANTIBODIES DISTINGUISH EPO-DEPENDENT AND EPO-INDEPENDENT ERYTHROID PROGENITORS IN POLYCYTHEMIA-VERA SO BLOOD LA English DT Article ID HUMAN MARROW; CELL-LINES; STEM-CELL; GROWTH; INVITRO; DIFFERENTIATION; ERYTHROCYTOSIS; EXPRESSION; BINDING; GENE AB Erythroid progenitor cells isolated from patients with polycythemia vera (PV) proliferate and differentiate in methylcellulose in the absence of exogenous erythropoietin (EPO). To investigate the potential role of the erythropoietin receptor (EPO-R) in the pathogenesis of PV, we cultured bone marrow-derived or peripheral blood-derived erythroid progenitors in the presence of neutralizing monoclonal antibodies (MoAbs) specific for EPO or EPO-R. Mononuclear cells were obtained from 9 healthy adults and 9 PV patients by Ficoll-Hypaque gradients and cultured with or without EPO in methylcellulose for 12 days under standard or serum-free conditions. Neutralizing anti-EPO and anti-EPO-R MoAbs, added to cultures at day 0, caused dose-dependent growth inhibition of all normal burst-forming units-erythroid (BFU-E) derived from healthy adult controls. The MoAbs had no effect on the growth of nonerythroid progenitor cells under the same culture conditions. In contrast, neutralizing antibodies distinguished two classes of BFU-E derived from PV patients. Class I BFU-E from PV patients were EPO-dependent. These progenitors, like those derived from healthy adults, had normal EPO dose-dependent growth characteristics and showed a normal period of EPO requirement in vitro that extended 6 days after the initiation of culture. These results indicate that EPO exerts its critical effect early during erythroid differentiation; the addition of neutralizing antibodies to normal progenitors after 6 days had no effect on the subsequent size or maturation of the colonies. Class II BFU-E from PV patients were EPO-independent. They proliferated and differentiated even in the presence of high concentrations of neutralizing anti-EPO or anti-EPO-R MoAbs. We conclude that the class II BFU-E from PV patients are independent of free EPO. (C) 1994 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. MCGILL UNIV,DEPT MED,MONTREAL,PQ,CANADA. MCGILL UNIV,DEPT ONCOL,MONTREAL,PQ,CANADA. UNIV ALABAMA,DEPT MED,DIV HEMATOL ONCOL,BIRMINGHAM,AL 35294. FU NIDDK NIH HHS [R01 DK 43889-01] NR 44 TC 60 Z9 61 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 1994 VL 84 IS 6 BP 1982 EP 1991 PG 10 WC Hematology SC Hematology GA PG388 UT WOS:A1994PG38800035 PM 8081000 ER PT J AU SCHNITT, SJ ABNER, A GELMAN, R CONNOLLY, JL RECHT, A DUDA, RB EBERLEIN, TJ MAYZEL, K SILVER, B HARRIS, JR AF SCHNITT, SJ ABNER, A GELMAN, R CONNOLLY, JL RECHT, A DUDA, RB EBERLEIN, TJ MAYZEL, K SILVER, B HARRIS, JR TI THE RELATIONSHIP BETWEEN MICROSCOPIC MARGINS OF RESECTION AND THE RISK OF LOCAL RECURRENCE IN PATIENTS WITH BREAST-CANCER TREATED WITH BREAST-CONSERVING SURGERY AND RADIATION-THERAPY SO CANCER LA English DT Article DE BREAST CANCER; LOCAL RECURRENCE; MARGINS; EXTENSIVE INTRADUCTAL COMPONENT ID CONSERVATIVE SURGERY; PATHOLOGIC FINDINGS; LUMPECTOMY; IRRADIATION; EXCISION; CARCINOMA; SIZE AB Background. The relationships among the involvement of tumor at the final margins of resection, the presence of an extensive intraductal component (EIC), and the risk of local recurrence are important considerations in patients treated with conservative surgery and radiation therapy for early stage breast cancer but have not been defined adequately. Methods. Between 1982 and 1985, 885 patients were treated for clinical Stage I or II invasive breast cancer. The study population was limited to 181 patients with an infiltrating ductal carcinoma who received a radiation dose to the surgical site of 60 Gy or greater, whose final microscopic margins of resection were evaluable, and who had at least 5 years of follow-up. A positive margin was defined as tumor present at the inked margin of resection, a close margin as tumor within 1 mm of the inked margin, and a negative margin as no tumor within 1 mm of the inked margin. A focally positive margin was defined as tumor at the margin in three or fewer low-power fields. In 157 patients (87%), the tumor was evaluable for the presence or absence of an EIC. The median follow-up was 86 months. Results. In 12 of 181 patients (7%), a recurrence developed at or near the primary site (true recurrence/marginal miss [TR/MM]) within 5 years. The 5-year rate of TR/MM (with 95% confidence intervals) among patients with negative, close, focally positive, and more than focally positive margins was 0% (0-4%), 4% (0-20%), 6% (1-17%) and 21% (10-37%), respectively. Patients with positive margins also were more likely to have a distant failure within 5 years (14%, 8%, 25%, and 32% in the four groups, respectively). However, patients with positive margins more often had positive axillary lymph nodes than patients with negative or close margins (59% vs. 38%, P < 0.02). The 5-year rate of TR/MM was 20% for patients with an EIC-positive tumor and 7% for patients with an EIC-negative tumor. However, among the 127 patients with an EIC-negative tumor, the 5-year rate of TR/MM was less than 10% in all margin groups. Among the 30 patients with an EIC-positive tumor, the 5-year rate of TR/MM was 0% when margins were negative or close but 50% when margins were more than focally positive. Conclusions. These results provide support for the use of breast-conserving surgery and breast irradiation in all patients with uninvolved margins, whether the tumor is EIC-positive or EIC-negative. This study suggests that breast-conserving therapy (including a radiation boost to the primary site) also may be a reasonable option for some patients with an EIC-negative tumor and margin involvement. C1 HARVARD UNIV,DANA FARBER CANC INST,CTR BREAST EVALUAT,BOSTON,MA. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV SURG ONCOL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02115. FAULKNER HOSP,FAULKNER BREAST CTR,BOSTON,MA. RP SCHNITT, SJ (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 19 TC 316 Z9 318 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD SEP 15 PY 1994 VL 74 IS 6 BP 1746 EP 1751 DI 10.1002/1097-0142(19940915)74:6<1746::AID-CNCR2820740617>3.0.CO;2-Y PG 6 WC Oncology SC Oncology GA PG098 UT WOS:A1994PG09800016 PM 8082077 ER PT J AU CORRALDEBRINSKI, M HORTON, T LOTT, MT SHOFFNER, JM MCKEE, AC BEAL, MF GRAHAM, BH WALLACE, DC AF CORRALDEBRINSKI, M HORTON, T LOTT, MT SHOFFNER, JM MCKEE, AC BEAL, MF GRAHAM, BH WALLACE, DC TI MARKED CHANGES IN MITOCHONDRIAL-DNA DELETION LEVELS IN ALZHEIMER BRAINS SO GENOMICS LA English DT Note ID APOLIPOPROTEIN-E; TYPE-4 ALLELE; HUMAN-HEART; DISEASE; AGE; ACCUMULATION; INCREASE; DEMENTIA; PATTERN; DAMAGE AB Levels of the common 4977 nucleotide pair (np) mitochondrial DNA (mtDNA) deletion (mtDNA(4977)) were quantitated in the cortex, putamen, and cerebellum of patients with Alzheimer disease (AD) and compared to age-matched controls. Although cerebellum deletion levels were comparably low in AD patients and controls of all ages, cortical deletion levels were clearly different. The levels of mtDNA deletions in control brains started low, but rose markedly after age 75, while those of AD patients started high and declined to low levels by age 80. Choosing age 75 to arbitrarily delineate between younger and older subjects, younger patients had 15 times more mtDNA deletions than younger controls, while older patients had one-fifth the deletion level of older controls. Younger AD patients also had fourfold more deletions than older AD patients. These results support the hypothesis that OXPHOS defects resulting from somatic mtDNA mutations may play a role in AD pathophysiology. (C) 1994 Academic Press, Inc. C1 EMORY UNIV,SCH MED,DEPT MOLEC & MED GENET,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. OI Graham, Brett/0000-0001-8451-8154 FU NCI NIH HHS [CA09329]; NCRR NIH HHS [M01RR-00039]; NIA NIH HHS [1P30AG10130] NR 25 TC 182 Z9 187 U1 3 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 15 PY 1994 VL 23 IS 2 BP 471 EP 476 DI 10.1006/geno.1994.1525 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PK060 UT WOS:A1994PK06000020 PM 7835898 ER PT J AU MENU, E TSAI, BC BOTHWELL, ALM SIMS, PJ BIERER, BE AF MENU, E TSAI, BC BOTHWELL, ALM SIMS, PJ BIERER, BE TI CD59 COSTIMULATION OF T-CELL ACTIVATION - CD58 DEPENDENCE AND REQUIREMENT FOR GLYCOSYLATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-3; PROTEIN TYROSINE KINASES; MEMBRANE ATTACK COMPLEX; LOW-AFFINITY LIGAND; ERYTHROCYTE RECEPTOR; MONOCLONAL-ANTIBODY; LYMPHOCYTE-T; BINDING-SITES; MOLECULE CD2; 2ND LIGAND AB In addition to the TCR-CD3 complex, T lymphocytes can be activated via another surface glycoprotein, the CD2 molecule. CD58 is the principal ligand for human CD2; CD59 and CD48 are two additional, low affinity ligands that have been defined for CD2. In this study, we have explored the role of CD59 in T cell activation. We have expressed human rCD58 and rCD59 molecules in Chinese hamster oocytes (CHO), and tested paraformaldehyde-treated transfectants for the ability to promote proliferation of and IL-2 secretion from PBMC and human purified T cells. We have shown that CD59 enhanced CD58-dependent T cell proliferation and IL-2 secretion in the presence of suboptimal concentration of PHA or a submitogenic combination of stimulatory anti-CD2 mAbs, T11-2 + T11-3. CD59-dependent costimulation was dependent on several factors including the level of coexpression of CD58, the ratio of CHO cell transfectants to T cells added in culture, the concentration of mitogen, and also donor-dependent differences. As expected, CD59 costimulation of CD58-dependent T cell proliferation was inhibited by Abs directed against CD59, CD58, and CD2. In our hands, the CD59 molecule itself, in the absence of CD58, was unable to support proliferation alone even in the presence of exogenous recombinant IL-1, IL-2, or IL-6. Finally, the ability of CD59 to enhance CD58-dependent T cell responses was shown to be dependent on N-glycosylation of CP59 at amino acid Asn18. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. YALE UNIV,SCH MED,IMMUNOBIOL SECT,NEW HAVEN,CT 06520. BLOOD RES INST SE WISCONSIN,MILWAUKEE,WI 53233. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI MENU, Elisabeth/B-2886-2010 OI MENU, Elisabeth/0000-0001-8844-9328 FU NHLBI NIH HHS [HL36031]; NIAID NIH HHS [AI28554] NR 42 TC 31 Z9 31 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1994 VL 153 IS 6 BP 2444 EP 2456 PG 13 WC Immunology SC Immunology GA PF189 UT WOS:A1994PF18900009 PM 7521361 ER PT J AU MANTHEY, CL PERERA, PY HENRICSON, BE HAMILTON, TA QURESHI, N VOGEL, SN AF MANTHEY, CL PERERA, PY HENRICSON, BE HAMILTON, TA QURESHI, N VOGEL, SN TI ENDOTOXIN-INDUCED EARLY GENE-EXPRESSION IN C3H/HEJ (LPS(D)) MACROPHAGES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOTYPE LIPOPOLYSACCHARIDE PREPARATIONS; PERMEABILITY-INCREASING PROTEIN; AMINO-TERMINAL FRAGMENT; LIPID-A; MURINE MACROPHAGES; TYROSINE PHOSPHORYLATION; GAMMA-INTERFERON; MONONUCLEAR PHAGOCYTES; PERITONEAL-MACROPHAGES; C3H-HEJ LYMPHOCYTES AB C3H/HeJ (Lps(d)) macrophages have been shown to respond to certain LPSs, especially from rough mutant bacteria. C3H/OuJ (Lps(n)) macrophages are induced by wild-type LPS, rough LPS, or lipid A to express many genes, including TNF-alpha, TNFR-2, IL-1 beta, IP-10, D3, and D8. C3H/HeJ macrophages failed to induce any of these genes when cultured with wild-type LPS or synthetic lipid A, even when pretreated with IFN-gamma. However, rough mutant Salmonella minnesota Ra, Rc, and Rd LPS, and Escherichia coli D31 m3 Rd LPS induced Lps(d) macrophages to express a subset of genes within the gene panel. Because bioactive preparations contained trace quantities of endotoxin protein(s), a deoxycholate-modified, phenol-water method was used to repurify rough LPS into an aqueous phase, and extract endotoxin proteins into a phenol phase. Repurified LPS failed to stimulate Lps(d) macrophages; however, phenol fractions were similar to 10% as potent in Lps(d) macrophages as crude rough LPS. Full potency was restored in C3H/HeJ macrophages when aqueous phase LPS and phenol-phase proteins were coprecipitated, suggesting that LPS and endotoxin proteins interact synergistically. Endotoxin proteins alone induced TNF-alpha, TNFR-2, and IL-1 beta, but not IP-10, D3, and D8 genes in both Lps(d) and Lps(n) macrophages. Tyrosine phosphorylation of three 41- to 47-kDa proteins was induced by endotoxin proteins, but not by LPS, in Lps(d) macrophages. Thus, endotoxin proteins seem to activate a signaling pathway(s) that converges (distal to the Lps gene product) with a subset of LPS-signaling pathways. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL & IMMUNOL,BETHESDA,MD 20814. CLEVELAND CLIN FDN,RES INST,CLEVELAND,OH 44195. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,MADISON,WI 53705. UNIV WISCONSIN,SCH AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. FU NCI NIH HHS [CA39621]; NIAID NIH HHS [AI-08451, AI-18797] NR 47 TC 106 Z9 106 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 1994 VL 153 IS 6 BP 2653 EP 2663 PG 11 WC Immunology SC Immunology GA PF189 UT WOS:A1994PF18900031 PM 7521367 ER PT J AU TSAI, FY KELLER, G KUO, FC WEISS, M CHEN, JZ ROSENBLATT, M ALT, FW ORKIN, SH AF TSAI, FY KELLER, G KUO, FC WEISS, M CHEN, JZ ROSENBLATT, M ALT, FW ORKIN, SH TI AN EARLY HEMATOPOIETIC DEFECT IN MICE LACKING THE TRANSCRIPTION FACTOR GATA-2 SO NATURE LA English DT Article ID EMBRYONIC STEM-CELLS; ERYTHROID-DIFFERENTIATION; TARGETED MUTATION; DEVELOPING MOUSE; DNA-BINDING; YOLK-SAC; ES CELLS; EXPRESSION; GENE; HEMATOPOIESIS AB Blood cell development relies on the expansion and maintenance of haematopoietic stem and progenitor cells in the embryo. By gene targeting in mouse embryonic stem cells, we demonstrate that the transcription factor GATA-2 plays a critical role in haematopoiesis, particularly of an adult type. We propose that GATA-2 regulates genes controlling growth factor responsiveness or the proliferative capacity of early haematopoietic cells. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,CTR BLOOD RES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO 80206. NR 39 TC 968 Z9 988 U1 2 U2 18 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 15 PY 1994 VL 371 IS 6494 BP 221 EP 226 DI 10.1038/371221a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PG290 UT WOS:A1994PG29000043 PM 8078582 ER PT J AU MORRISON, BW AF MORRISON, BW TI ADJUVANT THERAPY FOR BREAST-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP MORRISON, BW (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 15 PY 1994 VL 331 IS 11 BP 743 EP 744 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PF332 UT WOS:A1994PF33200018 PM 7914675 ER PT J AU GOLDHIRSCH, A GELBER, RD AF GOLDHIRSCH, A GELBER, RD TI ADJUVANT THERAPY FOR BREAST-CANCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP GOLDHIRSCH, A (reprint author), INT BREAST CANC STUDY GRP,CH-6900 LUGANO,SWITZERLAND. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 15 PY 1994 VL 331 IS 11 BP 745 EP 746 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PF332 UT WOS:A1994PF33200022 ER PT J AU FINKELSTEIN, DM SCHOENFELD, DA AF FINKELSTEIN, DM SCHOENFELD, DA TI ANALYZING SURVIVAL IN THE PRESENCE OF AN AUXILIARY VARIABLE SO STATISTICS IN MEDICINE LA English DT Article ID CLINICAL-TRIALS; STATISTICS AB A primary endpoint of AIDS trials is the length of survival. Often there is auxiliary information available on measures of disease progression, which significantly alter the risk of mortality. This paper explores the use of this information in obtaining a refined estimate of survival, and a test based on this estimate. The methods are applied to an AIDS clinical trial, and results of simulations are provided which compare the approach to standard methods for survival analysis. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP FINKELSTEIN, DM (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-30885, N0-AI-95030] NR 16 TC 38 Z9 39 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD SEP 15 PY 1994 VL 13 IS 17 BP 1747 EP 1754 DI 10.1002/sim.4780131706 PG 8 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PH158 UT WOS:A1994PH15800005 PM 7997708 ER PT J AU HANES, SD BRENT, R SUZUKI, M AF HANES, SD BRENT, R SUZUKI, M TI BACKWARD BICOID SO STRUCTURE LA English DT Letter ID HOMEODOMAIN RECOGNITION HELIX; CRYSTAL-STRUCTURE; DNA INTERACTIONS; COMPLEX; PROTEIN; MODEL C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MRC,MOLEC BIOL LAB,CAMBRIDGE CB2 2QH,ENGLAND. RP HANES, SD (reprint author), NEW YORK STATE DEPT HLTH,WADSWORTH CTR LABS & RES,AXELROD INST,ALBANY,NY 12208, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD SEP 15 PY 1994 VL 2 IS 9 BP 894 EP 894 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PJ407 UT WOS:A1994PJ40700014 PM 7812722 ER PT J AU PEPE, S BOGDANOV, K HALLAQ, H SPURGEON, H LEAF, A LAKATTA, E AF PEPE, S BOGDANOV, K HALLAQ, H SPURGEON, H LEAF, A LAKATTA, E TI OMEGA-3 POLYUNSATURATED FATTY-ACID MODULATES DIHYDROPYRIDINE EFFECTS ON L-TYPE CA2+ CHANNELS, CYTOSOLIC CA2+, AND CONTRACTION IN ADULT-RAT CARDIAC MYOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PATCH CLAMP RECORDING; INDO-1 FLUORESCENCE ID CALCIUM CHANNELS; ARACHIDONIC-ACID AB The effect of docosahexaenoic acid (DHA; C22:6) on dihydropyridine (DHP) interaction with L-type Ca2+ channel current (I-Ca), cytosolic Ca2+ (Ca-i), and cell contraction in isolated adult rat cardiac myocytes was studied. The DHP L-type Ca2+-channel blocker nitrendipine (10 nM) reduced peak I-Ca (measured by whole-cell voltage clamp from -45 to 0 mV) and reduced the amplitude of the Ca2+ transient (measured as the transient in indo-1 fluorescence, 410/490 nm) and the twitch amplitude (measured via photodiode array) during steady-state electrical stimulation (0.5 Hz). The DHP L-type Ca2+ channel agonist BAY K 8644 (10 nM) significantly increased I-Ca, the amplitude of the Ca-i transient, and contraction. When cells were exposed to DHA (5 mu M) simultaneously with either BAY K 8644 or nitrendipine, the drug effects were abolished. Arachidonic acid (C20:4) at 5 mu M did not block the inhibitory effects of nitrendipine nor did it prevent the potentiating effects of BAY K 8644. DHA modulation of DHP action could be reversed by cell perfusion with fatty acid-free bovine serum albumin at 1 mg/ml. Neither DHA nor arachidonic acid alone (5 mu M) had any apparent effect on the parameters measured. DHA (5 mu M) had no influence over beta-adrenergic receptor stimulation (isoproterenol, 0.01-1 mu M)-induced increases in I-Ca, Ca-i, or contraction. The findings that DHA inhibits the effect of DHP agonists and antagonists on Ca2+-channel current but has no effect alone or on beta-adrenergic-induced increases in I-Ca suggests that DHA specifically binds to Ca2+ channels at or near DHP binding sites and interferes with I-Ca modulation. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA 02132. FU NIDDK NIH HHS [DK38165] NR 14 TC 100 Z9 101 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 13 PY 1994 VL 91 IS 19 BP 8832 EP 8836 DI 10.1073/pnas.91.19.8832 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PG521 UT WOS:A1994PG52100021 PM 7522322 ER PT J AU GLAZEBROOK, J AUSUBEL, FM AF GLAZEBROOK, J AUSUBEL, FM TI ISOLATION OF PHYTOALEXIN-DEFICIENT MUTANTS OF ARABIDOPSIS-THALIANA AND CHARACTERIZATION OF THEIR INTERACTIONS WITH BACTERIAL PATHOGENS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PSEUDOMONAS SYRINGAE; AVIRULENCE; CAMALEXIN; PLANT DEFENSE ID AVIRULENCE GENE AVRRPT2; DISEASE RESISTANCE; PSEUDOMONAS; SYRINGAE; PLANT; IDENTIFICATION; MUTATIONS; INFECTION; RPS2 AB A genetic approach was used to assess the extent to which a particular plant defense response, phytoalexin biosynthesis, contributes to Arabidopsis thaliana resistance to Pseudomonas syringae pathogens. The A. thaliana phytoalexin, camalexin, accumulated in response to infection by various P. syringae strains. No correlation between pathogen avirulence and camalexin accumulation was observed. A biochemical screen was used to isolate three mutants of A. thaliana ecotype Columbia that were phytoalexin deficient Glad mutants). The mutations pad1, pad2, and pad3 were found to be recessive alleles of three different genes. pad1 and pad2 were mapped to chromosome IV and pad3 was mapped to chromosome III. Infection of pad mutant plants with strains carrying cloned avirulence genes revealed that the pad mutations did not affect the plants' ability to restrict the growth of these strains. This result strongly suggests that in A. thaliana, phytoalexin biosynthesis is not required for resistance to avirulent P. syringae pathogens. Two of the pad mutants displayed enhanced sensitivity to isogenic virulent P. syringae pathogens, suggesting that camalexin may serve to limit the growth of virulent bacteria. C1 MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. RP GLAZEBROOK, J (reprint author), HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02114 USA. RI allasia, valerie/B-4214-2009; OI Glazebrook, Jane/0000-0001-5167-736X FU NIGMS NIH HHS [GM48707] NR 23 TC 298 Z9 304 U1 2 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 13 PY 1994 VL 91 IS 19 BP 8955 EP 8959 DI 10.1073/pnas.91.19.8955 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PG521 UT WOS:A1994PG52100046 PM 8090752 ER PT J AU EMANUEL, EJ AF EMANUEL, EJ TI EUTHANASIA - HISTORICAL, ETHICAL, AND EMPIRIC PERSPECTIVES SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID VOLUNTARY ACTIVE EUTHANASIA; ASSISTED SUICIDE; PHYSICIANS AID; NETHERLANDS; LIFE; DEATH; ATTITUDES AB Debates about the ethics of euthanasia date from ancient Greece and Rome. In 1870, S. D. Williams, a nonphysician, proposed that anesthetics be used to intentionally end the lives of patients. Between 1870 and 1936, a debate about the ethics of euthanasia raged in the United States and Britain. These debates predate and invoke different arguments than do debates about euthanasia in Germany. Recognizing the increased interest in euthanasia, this article reviews the definitions related to euthanasia, the historical record of debates concerning euthanasia, the arguments for and against euthanasia, the situation in the Netherlands, and the empirical data regarding euthanasia in the United States. C1 HARVARD UNIV,SCH MED,DIV MED ETH,BOSTON,MA. RP EMANUEL, EJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC CONTROL & EPIDEMIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 113 TC 79 Z9 80 U1 0 U2 20 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 12 PY 1994 VL 154 IS 17 BP 1890 EP 1901 DI 10.1001/archinte.154.17.1890 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA PF679 UT WOS:A1994PF67900001 PM 8074593 ER PT J AU SIMON, B TILLOTSON, L BRAND, SJ AF SIMON, B TILLOTSON, L BRAND, SJ TI ACTIVATION OF GASTRIN GENE-TRANSCRIPTION IN ISLET CELLS BY A RAP1-LIKE CIS-ACTING PROMOTER ELEMENT SO FEBS LETTERS LA English DT Article DE TRANSCRIPTION FACTOR; GASTRIN PROMOTER; ISLET CELL; RAP1 ID DNA-BINDING PROTEIN; SACCHAROMYCES-CEREVISIAE; YEAST SILENCER; RNA-POLYMERASE; GROWTH-FACTOR; PGK GENE; RAP1; EXPRESSION; SEQUENCES; IDENTIFICATION AB Gastrin transcription in islet cells is activated by a cis-regulatory sequence containing a binding site for the yeast transcription factor RAP1. The DNA-protein interactions between RAP1 protein and the gastrin DNA element determined by methylation interference assays are identical to those of RAP1 and yeast genes. Point mutations in the gastrin RAP1 binding site, which abolished RAP1 binding, decreased transcriptional activation by this sequence. Islet cells revealed a DNA binding protein with RAP1-like binding specificity. These findings support the conclusion that gastrin transcription is activated in mammalian cells by a RAP1-like transcription factor. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. RP SIMON, B (reprint author), UNIV MARBURG,DEPT INTERNAL MED,DIV GASTROENTEROL,BALDINGERSTR,D-35033 MARBURG,GERMANY. NR 38 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 12 PY 1994 VL 351 IS 3 BP 340 EP 344 DI 10.1016/0014-5793(94)00862-0 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PG938 UT WOS:A1994PG93800011 PM 8082791 ER PT J AU ROCK, KL GRAMM, C ROTHSTEIN, L CLARK, K STEIN, R DICK, L HWANG, D GOLDBERG, AL AF ROCK, KL GRAMM, C ROTHSTEIN, L CLARK, K STEIN, R DICK, L HWANG, D GOLDBERG, AL TI INHIBITORS OF THE PROTEASOME BLOCK THE DEGRADATION OF MOST CELL-PROTEINS AND THE GENERATION OF PEPTIDES PRESENTED ON MHC CLASS-I MOLECULES SO CELL LA English DT Article ID ATP-DEPENDENT PROTEOLYSIS; ANTIGEN PRESENTATION; LYMPHOCYTE-T; HEAVY-CHAINS; COMPLEX; PATHWAY; GENE; DETERMINANTS; EXPRESSION; ANTIBODIES AB Reagents that inhibit the ubiquitin-proteasome proteolytic pathway in cells have not been available. Peptide aldehydes that inhibit major peptidase activities of the 20S and 26S proteasomes are shown to reduce the degradation of protein and ubiquitinated protein substrates by 26S particles. Unlike inhibitors of lysosomal proteolysis, these compounds inhibit the degradation of not only abnormal and short-lived polypeptides but also long-lived proteins in intact cells. We used these agents to test the importance of the proteasome in antigen presentation. When ovalbumin is introduced into the cytosol of lymphoblasts, these inhibitors block the presentation on MHC class I molecules of an ovalbumin-derived peptide by preventing its proteolytic generation. By preventing peptide production from cell proteins, these inhibitors block the assembly of class I molecules. Therefore, the proteasome catalyzes the degradation of the vast majority of cell proteins and generates most peptides presented on MHC class I molecules. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. MYOGEN INC,CAMBRIDGE,MA 02139. RP ROCK, KL (reprint author), DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115, USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NIAID NIH HHS [AI20248]; NIGMS NIH HHS [GM46147] NR 45 TC 1912 Z9 1932 U1 9 U2 69 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD SEP 9 PY 1994 VL 78 IS 5 BP 761 EP 771 DI 10.1016/S0092-8674(94)90462-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PG296 UT WOS:A1994PG29600006 PM 8087844 ER PT J AU MATSUOKA, Y CHEN, SY COMPANS, RW AF MATSUOKA, Y CHEN, SY COMPANS, RW TI A SIGNAL FOR GOLGI RETENTION IN THE BUNYAVIRUS G1 GLYCOPROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PUNTA-TORO VIRUS; BETA-GALACTOSIDE ALPHA-2,6-SIALYLTRANSFERASE; MEMBRANE-SPANNING DOMAIN; ENDOPLASMIC-RETICULUM; TRANSMEMBRANE DOMAIN; INTRACELLULAR-TRANSPORT; ENVELOPE GLYCOPROTEIN; CYTOPLASMIC DOMAINS; PROTEIN-TRANSPORT; COMPLEX AB The G1 and G2 glycoproteins of Punta Toro virus, a member of the bunyaviruses, are targeted to the Golgi complex, where viral budding occurs. We found that the G1 protein, when expressed in the absence of G2, is also targeted to the Golgi complex. A series of G1 proteins truncated at the carboxyl-terminal region was constructed, and the localization of the expressed proteins was examined. It was found that the proteins expressed from constructs with partial deletions in the cytoplasmic domain were transported to the Golgi complex at a significantly slower rate than G1. Although a major fraction of these proteins was eventually transported to the Golgi complex, they did not exhibit as clearly defined a pattern of accumulation as G1, but rather appeared to be distributed throughout the endoplasmic reticulum as well as the Golgi complex. The proteins expressed from constructs lacking most of the cytoplasmic domain and, in some cases, part of the transmembrane domain sequences as well were transported to the cell surface. We have also constructed chimeric proteins with the envelope protein of a murine leukemia virus (MCFenv), which is efficiently transported to the plasma membrane. A MCF G1 chimera that contained the G1 transmembrane and cytoplasmic domains was found to be efficiently retained in the Golgi complex, and a construct that contained only the G1 transmembrane domain was also partially retained in the Golgi complex. Thus, the transmembrane domain as well as a portion of the cytoplasmic domain adjacent to the transmembrane domain are apparently crucial for Golgi retention of the G1 protein. C1 EMORY UNIV,DEPT MICROBIOL & IMMUNOL,ATLANTA,GA 30322. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. RI Compans, Richard/I-4087-2013 OI Compans, Richard/0000-0003-2360-335X FU NCI NIH HHS [NCI CA-18611]; NIAID NIH HHS [NIAID AI-12680] NR 49 TC 49 Z9 50 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 9 PY 1994 VL 269 IS 36 BP 22565 EP 22573 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ163 UT WOS:A1994PQ16300020 PM 8077205 ER PT J AU BELL, LM SOLOMON, KR GOLD, JP TAN, KN AF BELL, LM SOLOMON, KR GOLD, JP TAN, KN TI CYTOPLASMIC TAIL DELETION OF T-CELL RECEPTOR (TCR) BETA-CHAIN RESULTS IN ITS SURFACE EXPRESSION AS GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED POLYPEPTIDE ON MATURE T-CELLS IN THE ABSENCE OF TCR-ALPHA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE AMINO-ACID; ANTIGEN RECEPTOR; ENDOPLASMIC-RETICULUM; GLYCOSYL-PHOSPHATIDYLINOSITOL; MONOCLONAL-ANTIBODIES; MEMBRANE-PROTEIN; COMPLEX; DEGRADATION; REQUIREMENTS; RETENTION AB Surface expression of the T cell antigen receptor (TCR) in mature T cells requires the association of a variable heterodimer (alpha.beta or gamma.delta) with six invariant CD3 polypeptides (gamma, delta, epsilon-epsilon, zeta-zeta, or zeta-eta). We describe here that deletion of the cytoplasmic tail polypeptide sequence (Lys-Lys-Lys-Asn-Ser) of TCR beta-chain (beta(CT)) results in expression of the truncated beta-chain on the surface of a mature T cell hybridoma line, in the absence of TCR-alpha, as a glycophosphatidylinositol (GPI)-anchored monomeric polypeptide. The GPI-anchored TCR-beta(CT) is not associated with CD3-epsilon and is incapable of conventional signal transduction. Association with TCR-alpha prevents beta(CT) from GPI-linkage formation. The alpha beta(CT) heterodimer binds the CD3 polypeptides, and the resultant TCR alpha beta(CT)/CD3 complex is capable of signal transduction. Our data show that a signal sequence for GPI-linkage formation is present in TCR-beta, and this alternative membrane anchoring mechanism can be utilized by beta-chain polypeptide lacking the CT sequence. We conclude therefore that in the absence of TCR-alpha expression, the beta-chain CT sequence plays an essential function in hindering GPI-Linkage formation, thereby preventing escape of incompletely assembled TCR beta-chain to the cell surface of mature T cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI-27983] NR 50 TC 9 Z9 9 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 9 PY 1994 VL 269 IS 36 BP 22758 EP 22763 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PQ163 UT WOS:A1994PQ16300047 PM 8077227 ER PT J AU EAGLE, KA FALLON, JT DRUCKER, EA BECK, WS MORRIS, DG FRAENKEL, P AF EAGLE, KA FALLON, JT DRUCKER, EA BECK, WS MORRIS, DG FRAENKEL, P TI A 41-YEAR-OLD WOMAN WITH THROMBOCYTOPENIA, ANEMIA, AND SUDDEN-DEATH - THROMBOTIC THROMBOCYTOPENIC PURPURA, WITH ASSOCIATED EXTENSIVE ACUTE MYOCARDIAL NECROSIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ENDOTHELIAL-CELLS; PLASMA-EXCHANGE; PATIENT; PLASMAPHERESIS; EXPERIENCE; INFUSION C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP EAGLE, KA (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 25 TC 14 Z9 14 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 8 PY 1994 VL 331 IS 10 BP 661 EP 667 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PE382 UT WOS:A1994PE38200008 ER PT J AU KALIN, NH TAKAHASHI, LK CHEN, FL AF KALIN, NH TAKAHASHI, LK CHEN, FL TI RESTRAINT STRESS INCREASES CORTICOTROPIN-RELEASING HORMONE MESSENGER-RNA CONTENT IN THE AMYGDALA AND PARAVENTRICULAR NUCLEUS SO BRAIN RESEARCH LA English DT Note DE STRESS; CORTICOTROPIN RELEASING HORMONE; MESSENGER-RNA; AMYGDALA; HYPOTHALAMUS ID FACTOR-LIKE IMMUNOREACTIVITY; MESSENGER RIBONUCLEIC-ACID; RAT-BRAIN REGIONS; DIFFERENTIAL REGULATION; FACTOR RECEPTORS; RNA; RESPONSES; CATECHOLAMINES; HYPOTHALAMUS; ANTAGONISM AB Corticotropin-releasing hormone (CRH) neurons located in the paraventricular nucleus (PVN) of the hypothalamus are implicated in regulating the endocrine response to stress. The amygdala is an established component of the neural circuitry mediating the stress response, To obtain information concerning the effects of stress on amygdala CRH neurons, a time-course study was conducted to examine, in rats, whether a 1-h restraint period increases CRH mRNA levels. The effects of restraint were also measured in the PVN. Using a sensitive RNase protection assay, we found that CRH mRNA levels in both the amygdala and paraventricular nucleus were significantly elevated 1 h after cessation of restraint. CRH mRNA levels in the paraventricular nucleus, but not the amygdala, remained elevated at the 3-h post-stress interval. 48 h after the termination of restraint, CRH mRNA levels in both brain structures returned to control levels. These data provide the first direct evidence that stress activates amygdala CRH neurons. C1 UNIV WISCONSIN,DEPT PSYCHOL,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53792. RP KALIN, NH (reprint author), UNIV WISCONSIN,DEPT PSYCHIAT,MADISON,WI 53792, USA. FU NIMH NIH HHS [MH-40855] NR 24 TC 169 Z9 172 U1 1 U2 7 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 5 PY 1994 VL 656 IS 1 BP 182 EP 186 DI 10.1016/0006-8993(94)91382-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA PD957 UT WOS:A1994PD95700023 PM 7804835 ER PT J AU SHAEFFER, JR AF SHAEFFER, JR TI MONOUBIQUITINATED ALPHA-GLOBIN IS AN INTERMEDIATE IN THE ATP-DEPENDENT PROTEOLYSIS OF ALPHA-GLOBIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN SYSTEM; PROTEINS; CHAINS; DEGRADATION; PATHWAY; RETICULOCYTES; PURIFICATION; RECOGNITION; ENZYME AB A dialyzed whole human reticulocyte (beta-thalassemic) lysate was incubated with human I-125-alpha globin at 37 degrees C for 15 min in a medium supporting proteolysis with ATP and added ubiquitin (Ub). Analysis of this reaction mixture by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that similar to 0.5% of the initial I-125-alpha globin substrate radioactivity (I-125 cpm) was in the conjugate (Ub(1)-alpha) of one Ub monomer with one I-125-alpha globin monomer and substantially less in the Ub(2)-alpha conjugate. When the reaction mixture contained 0.5 mu M ubiquitin aldehyde (Ubal) to inhibit endogenous isopeptidases, there was a 7-9-fold increase in the Ub(1)-alpha and Ub(2)-alpha conjugates and an appearance of higher molecular weight species including polyubiquitinated I-125-alpha globin (Ub(>10)-alpha). Purified fractions of Ub(1)-alpha, Ub(2)-alpha, Ub(3,4)-alpha, and Ub(>10)-alpha conjugates were isolated by preparative SDS PAGE, dialyzed and treated with triethylamine to remove SDS, and dissolved in 10 mM HCOO-(Na+), pH 4.0. Incubation of each of the conjugate fractions with Ubal-treated lysate in a proteolysis reaction mixture showed a progressive increase in the initial rate of degradation (conversion to acid-soluble I-125 cpm) with increase in molar amount of Ub from similar to 3 times that of the unconjugated I-125-alpha globin precursor for Ub(1)-alpha to similar to 6 times for Ub(>10)-alpha. Analytical SDS-PAGE of the Ub(1)-alpha mixture also showed a rapid conversion to higher M(r) conjugates. These results suggest that monoubiquitinated alpha globin, in addition to higher M(r) conjugates, is an intermediate in the ATP-dependent proteolysis of alpha globin. The finding that addition of Ubal enhances the amount of these conjugates suggests that isopeptidase activity contributes to the poor turnover of hemoglobin alpha chains observed in intact beta-thalassemic reticulocytes. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. RP SHAEFFER, JR (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL29379] NR 32 TC 14 Z9 14 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 2 PY 1994 VL 269 IS 35 BP 22205 EP 22210 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE098 UT WOS:A1994PE09800045 PM 8071345 ER PT J AU LO, SH AN, Q BAO, SD WONG, WK LIU, Y JANMEY, PA HARTWIG, JH CHEN, LB AF LO, SH AN, Q BAO, SD WONG, WK LIU, Y JANMEY, PA HARTWIG, JH CHEN, LB TI MOLECULAR-CLONING OF CHICK CARDIAC-MUSCLE TENSIN - FULL-LENGTH CDNA SEQUENCE, EXPRESSION, AND CHARACTERIZATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADHERENS-TYPE JUNCTIONS; PHOSPHOTYROSINE-CONTAINING PROTEINS; CRK ONCOGENE PRODUCT; TYROSINE PHOSPHORYLATION; ERYTHROPOIETIN RECEPTOR; SMOOTH-MUSCLE; EXTRACELLULAR-MATRIX; ACTIN POLYMERIZATION; ELECTRON-MICROSCOPY; DEPENDENT MANNER AB Here we describe the molecular cloning of 7.1-kilobase cDNA encoding chick cardiac muscle tensin. It contains an open reading frame of 1,744 amino acid (aa) residues. Sequence analysis reveals that, in addition to the previously noted SH2 domain (Davis, S., Lu, M. L., Lo, S. H., Lin, S., Butler, J. A., Druker, B. J., Roberts, T. M., An, Q., and Chen, L. B. (1991) Science 252, 712-715), tensin contains virtually all of the known sequence (362 aa) of insertin, an actin-capping protein that allows actin monomer to be ''inserted'' (Schroer, E., and Wegner, A. (1985) Eur. J. Biochem. 153, 515-520). Moreover, tensin shares partial homology with actin (46.7% identity in 30 aa), beta-spectrin's actin-binding consensus (40% identity in 26 aa), BCR (40% identity in 25 aa), catenin alpha (35% identity in 45 aa), synapsin Ia (25.6% identity in 156 aa), IL-3 receptor (20.2% identity in 384 aa), and IL-2/EPO receptors (14% identity in 20 aa). Recombinant full-length tensin, tagged with an influenza-derived epitope, was overexpressed by a baculovirus system and purified to apparent homogeneity. It migrates as a 200-kDa protein in SDS-polyacrylamide gel electrophoresis, similar to the native tensin. The structure of the tensin molecule has been characterized by light scattering, electron microscopy, and gel filtration. Nine monoclonal antibodies recognizing different regions of tensin have been prepared and characterized. The epitope-tagged recombinant tensin gene was subcloned into a pRcCMV vector and transfected into NIH3T3 cells. Immunofluorescence stainings with monoclonal antibodies specific for chick tensin (not cross-reactive with mouse tensin) showed that the expressed protein is indeed localized at focal contacts, as that of native tensin. RP LO, SH (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL 47874]; NIDDK NIH HHS [DK 38452]; NIGMS NIH HHS [GM 38318] NR 58 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 2 PY 1994 VL 269 IS 35 BP 22310 EP 22319 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PE098 UT WOS:A1994PE09800059 PM 8071358 ER PT J AU SIBER, GR AF SIBER, GR TI PNEUMOCOCCAL DISEASE - PROSPECTS FOR A NEW-GENERATION OF VACCINES SO SCIENCE LA English DT Editorial Material ID MEMBRANE PROTEIN COMPLEX; STREPTOCOCCUS-PNEUMONIAE; NEISSERIA-MENINGITIDIS; POLYSACCHARIDE VACCINE; CONJUGATE VACCINES; B POLYSACCHARIDE; INFANTS; IMMUNOGENICITY; INFECTIONS; ANTIBODIES C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02111. RP SIBER, GR (reprint author), MASSACHUSETTS PUBL HLTH BIOL LABS,BOSTON,MA 02111, USA. NR 20 TC 153 Z9 155 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 2 PY 1994 VL 265 IS 5177 BP 1385 EP 1387 DI 10.1126/science.8073278 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE733 UT WOS:A1994PE73300030 PM 8073278 ER PT J AU BUSH, AI PETTINGELL, WH MULTHAUP, G PARADIS, MD VONSATTEL, JP GUSELLA, JF BEYREUTHER, K MASTERS, CL TANZI, RE AF BUSH, AI PETTINGELL, WH MULTHAUP, G PARADIS, MD VONSATTEL, JP GUSELLA, JF BEYREUTHER, K MASTERS, CL TANZI, RE TI RAPID INDUCTION OF ALZHEIMER A-BETA AMYLOID FORMATION BY ZINC SO SCIENCE LA English DT Article ID PRECURSOR PROTEIN GENE; CEREBRAL-HEMORRHAGE; DOWNS-SYNDROME; DISEASE; MUTATION; PEPTIDE; BRAIN; AGGREGATION; DEMENTIA; HIPPOCAMPUS AB A beta(1-40), a major component of Alzheimer's disease cerebral amyloid, is present in the cerebrospinal fluid and remains relatively soluble at high concentrations (less than or equal to 3.7 mM). Thus, physiological factors which induce A beta amyloid formation could provide clues to the pathogenesis of the disease. It has been shown that human A beta specifically and saturably binds zinc. Here, concentrations of zinc above 300 nM rapidly destabilized human A beta(1-40) solutions, inducing tinctorial amyloid formation. However, rat A beta(1-40) binds zinc less avidly and is immune to these effects, perhaps explaining the scarcity with which these animals form cerebral A beta amyloid. These data suggest a role for cerebral zinc metabolism in the neuropathogenesis of Alzheimer's disease. C1 MASSACHUSETTS GEN HOSP,GENET & AGING LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. UNIV HEIDELBERG,ZENTRUM MOLEK BIOL HEIDELBERG,HEIDELBERG,GERMANY. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. UNIV MELBOURNE,DEPT PATHOL,PARKVILLE,VIC 3052,AUSTRALIA. MENTAL HLTH RES INST VICTORIA,PARKVILLE,VIC,AUSTRALIA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [R01 AG11899-01]; NINDS NIH HHS [R01 NS30428-03] NR 39 TC 1047 Z9 1069 U1 7 U2 73 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 2 PY 1994 VL 265 IS 5177 BP 1464 EP 1467 DI 10.1126/science.8073293 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PE733 UT WOS:A1994PE73300054 PM 8073293 ER PT J AU GRANADOS, R CIBAS, ES FLETCHER, JA AF GRANADOS, R CIBAS, ES FLETCHER, JA TI CYTOGENETIC ANALYSIS OF EFFUSIONS FROM MALIGNANT MESOTHELIOMA A DIAGNOSTIC ADJUNCT TO CYTOLOGY SO ACTA CYTOLOGICA LA English DT Article DE CYTOGENETICS; PLEURAL EFFUSION; MESOTHELIOMA ID PLEURAL MESOTHELIOMA; SEROUS EFFUSIONS; CELLS; PROTEINS; TUMORS; BENIGN AB Most patients with malignant mesothelioma (MM) present with an effusion, but distinguishing malignant from reactive mesothelial cells by conventional cytology may be difficult. We investigated the possibility of identifying clonal cytogenetic aberrations in pleural or peritoneal fluid from 10 patients with a clinical suspicion of MM. Direct metaphase harvests and shout-term cultures were performed on fresh fluid. Clonal cytogenetic aberrations indicative of malignancy, with findings previously reported in association with mesothelioma, were found in all patients; these included del(1p), del(3p) and del(22q). Cytologic examination of the effusions showed malignant cells consistent with MM in 5 patients and atypical mesothelial cells suggestive of MM in 4. In one case the cytology of several samples of pleural fluid was within normal limits. Subsequent histology confirmed the diagnosis of MM in 9 of the 10 patients; medical complications precluded tissue biopsy in the 10th. We conclude that the cytogenetic analysis of effusions may be a useful and reliable adjunct to cytology in the diagnosis of MM. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,CYTOL LAB,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 26 TC 23 Z9 23 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0001-5547 J9 ACTA CYTOL JI Acta Cytol. PD SEP-OCT PY 1994 VL 38 IS 5 BP 711 EP 717 PG 7 WC Pathology SC Pathology GA PH872 UT WOS:A1994PH87200009 PM 8091903 ER PT J AU KIKUCHI, T ADAMS, JC PAUL, DL KIMURA, RS AF KIKUCHI, T ADAMS, JC PAUL, DL KIMURA, RS TI GAP JUNCTION SYSTEMS IN THE RAT VESTIBULAR LABYRINTH - IMMUNOHISTOCHEMICAL AND ULTRASTRUCTURAL ANALYSIS SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE CONNEXIN26; EPITHELIAL CELL GAP JUNCTION SYSTEM; CONNECTIVE TISSUE CELL GAP JUNCTION SYSTEM ID SUPPORTING CELLS; FREEZE-FRACTURE; INNER-EAR; FIBROCYTES; GOLDFISH; SACCULE AB The distribution of gap junctions within the vestibular labyrinth was investigated using immunohistochemistry and transmission electron microscopy. Connexin26-like immunoreactivity was observed among supporting cells in each vestibular sensory epithelium. Reaction product was also present in the transitional epithelium of each vestibular endorgan and in the planum semilunatum of crista ampullaris. No connexin26-like immunoreactivity was observed among thin wall epithelial cells or among vestibular dark cells. In addition, fibrocytes within vestibular connective tissue were positively immunostained. Reaction product was also detected in the melanocyte area just beneath dark cells. Ultrastructural observations indicated that a gap junction network of vestibular supporting cells extends to the transitional epithelium and planum semilunatum and forms an isolated epithelial cell gap junction system in each vestibular endorgan. In contrast, no gap junctions were found among wall epithelial cells or among dark cells. Fibrocytes and melanocytes were coupled by gap junctions and belong to the connective tissue cell gap junction system, which is continuous throughout the vestibular system and the cochlea. The possible functional significance of these gap junction systems is discussed. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. FU NIDCD NIH HHS [R01 DC00073] NR 25 TC 66 Z9 69 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD SEP PY 1994 VL 114 IS 5 BP 520 EP 528 DI 10.3109/00016489409126097 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA PM957 UT WOS:A1994PM95700010 PM 7825434 ER PT J AU RIVERA, JM MELE, D VANDERVOORT, PM MORRIS, E WEYMAN, A THOMAS, JD AF RIVERA, JM MELE, D VANDERVOORT, PM MORRIS, E WEYMAN, A THOMAS, JD TI PHYSICAL FACTORS DETERMINING MITRAL REGURGITATION JET AREA SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID TRICUSPID REGURGITATION; VALVULAR REGURGITATION; QUANTIFICATION; FLOW; MOMENTUM C1 CLEVELAND CLIN FDN,DEPT CARDIOL,CLEVELAND,OH 44195. MASSACHUSETTS GEN HOSP,NONINVASIVE CARIDAC LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI rivera, miguel/D-5026-2014 NR 10 TC 5 Z9 5 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 1994 VL 74 IS 5 BP 515 EP 516 DI 10.1016/0002-9149(94)90920-2 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PD588 UT WOS:A1994PD58800026 PM 8059742 ER PT J AU RABENECK, L AF RABENECK, L TI BECAUSE ITS THERE - IT WAS MALLORY, NOT HILLARY SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter RP RABENECK, L (reprint author), DEPT VET AFFAIRS MED CTR,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD SEP PY 1994 VL 89 IS 9 BP 1601 EP 1601 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PE994 UT WOS:A1994PE99400054 PM 8079958 ER PT J AU LEUCHTER, A SIMON, SL DALY, KA ABRAMS, M ROSENBERGTHOMPSON, S DUNKIN, JJ COOK, IA NEWTON, TF SPAR, JE AF LEUCHTER, A SIMON, SL DALY, KA ABRAMS, M ROSENBERGTHOMPSON, S DUNKIN, JJ COOK, IA NEWTON, TF SPAR, JE TI QUANTITATIVE EEG CORRELATES OF OUTCOME IN OLDER PSYCHIATRIC-PATIENTS .2. 2-YEAR FOLLOW-UP OF PATIENTS WITH DEPRESSION SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID LATE-LIFE DEPRESSION; GERIATRIC DEPRESSION; COGNITIVE IMPAIRMENT; REVERSIBLE DEMENTIA; PROGNOSIS; AGE; RELAPSE; ILLNESS AB The authors examined quantitative electroencephalographic (QEEG) coherence in 3 7 depressed elderly patients and performed 2-year follow-up evaluations. All subjects had equivocal cognitive impairment, but none had delirium or dementia. More than 40% (16/37) recovered from depression, and 38% (14/37) remained well for 2 years. Twenty-four percent (n = 9) had died within 2 years, most from cardiac causes. Low trans-Rolandic coherence from the left hemisphere was strongly associated with mortality: 44% (7/16) of those with low coherence died, and 78% (7/9) of those who died had low coherence. Among survivors (n = 28) at follow-up, low coherence was significantly associated with lower functional status. These findings suggest that the coherence variable measures actual neurophysiologic differences between groups of depressed patients and these differences are associated with the heterogeneous outcomes of depression in elderly patients. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT PSYCHIAT & BIOBEHAV SCI, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL, LOS ANGELES, CA USA. W LOS ANGELES VA MED CTR, PSYCHIAT SERV, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, NEUROPSYCHIAT INST & HOSP, QUANTITAT EEG LAB, LOS ANGELES, CA USA. NR 46 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FAL PY 1994 VL 2 IS 4 BP 290 EP 299 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA PJ695 UT WOS:A1994PJ69500004 ER PT J AU BARSKY, AJ CLEARY, PD BARNETT, MC CHRISTIANSEN, CL RUSKIN, JN AF BARSKY, AJ CLEARY, PD BARNETT, MC CHRISTIANSEN, CL RUSKIN, JN TI THE ACCURACY OF SYMPTOM REPORTING BY PATIENTS COMPLAINING OF PALPITATIONS SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CARDIAC-ARRHYTHMIAS; AMBULATORY PATIENTS; HEALTH; HYPOCHONDRIASIS; SEVERITY; DISEASE; ANXIETY; ULCER AB PURPOSE: To examine the relationship between patients' reports of palpitations and documented arrhythmias. PATIENTS AND METHODS: Consecutive patients complaining of palpitations and referred for 24-hour ambulatory electrocardiographic monitoring were studied using self-report questionnaires and a structured diagnostic interview. Electrocardiographic results were subsequently analyzed in conjunction with symptom diaries. Positive predictive value was used to estimate the likelihood that a reported symptom coincided with a documented arrhythmia. Sensitivity was calculated as a measure of the likelihood that an arrhythmia would be detected and reported as a symptom. RESULTS: Positive predictive value was inversely related to somatization, hypochondriacal attitudes, and psychiatric symptoms. it was not related to chronicity of palpitations, previously diagnosed heart disease, more extensive medical care utilization, or clinically significant arrhythmias. Patients were generally insensitive to their arrhythmias, failing to note the vast majority. CONCLUSIONS: Somatizing and hypochondriacal patients are not more sensitive to or accurately aware of subtle changes in cardiac activity, but rather may be expressing a response bias toward reporting somatic and psychologic distress in general. Apparently, patients do not learn to discriminate and detect cardiac activity more accurately as a result of having more medical care or suffering longer with their symptoms. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV,CARDIAC UNIT,BOSTON,MA 02115. RP BARSKY, AJ (reprint author), BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,75 FRANCIS ST,BOSTON,MA 02115, USA. FU AHRQ HHS [HS-07118]; NHLBI NIH HHS [HL43216] NR 45 TC 33 Z9 36 U1 2 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1994 VL 97 IS 3 BP 214 EP 221 DI 10.1016/0002-9343(94)90003-5 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA PG635 UT WOS:A1994PG63500005 PM 8092169 ER PT J AU LEELEWANDROWSKI, E LAPOSATA, M ESCHENBACH, K CAMOOSO, C NATHAN, DM GODINE, JE HURXTHAL, K GOFF, J LEWANDROWSKI, K AF LEELEWANDROWSKI, E LAPOSATA, M ESCHENBACH, K CAMOOSO, C NATHAN, DM GODINE, JE HURXTHAL, K GOFF, J LEWANDROWSKI, K TI UTILIZATION AND COST-ANALYSIS OF BEDSIDE CAPILLARY GLUCOSE TESTING IN A LARGE TEACHING HOSPITAL - IMPLICATIONS FOR MANAGING POINT OF CARE TESTING SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID BLOOD-GLUCOSE AB PURPOSE: To study the use and cost of bedside capillary glucose testing in a large teaching hospital. PATIENTS AND METHODS: In a prospective study of 40 inpatient units and 10 outpatient units at Massachusetts General Hospital, records were maintained by each unit of the date, time, operator, and results of patient and quality control tests. Cost analysis was performed using data from time studies, test tallies in logbooks, and hospital administration records. RESULTS: The number of glucose meters in the hospital increased from 10 to 54 over a 2-year period. In 1992, 67,596 tests were performed by the bedside method, representing 30.7% of all glucose measurements performed in the institution. The majority of tests (94.7%) were performed on inpatients, and 10.2% of all hospital admissions underwent bedside glucose testing. The impact on the number of glucose tests performed in the clinical laboratories was minimal, indicating that bedside glucose testing was added as an extra test rather than as a substitute for laboratory-based glucose measurements. The cost of bedside glucose testing was $4.19 per test compared with $3.84 in the clinical laboratory. The cost varied from one unit to another (median $5.52, range $3.08 to $48.16), an effect largely attributed to the difference in the volume of tests performed by different units. In seven high-volume units the cost per test was lower than the corresponding value in the laboratory. The cost of bedside glucose testing included labor (80.2%) and supplies (19.8%). The percent of costs attributed directly to patient testing was 57.7%, whereas the costs for all other related activities (training, quality control, and quality assurance) was 42.3%. CONCLUSIONS: Bedside capillary glucose testing is a rapidly expanding technology and is performed on a significant percentage of hospital admissions. Bedside glucose testing is not inherently more expensive than centralized laboratory measurements but implementation on inefficient care units with low utilization can add substantially to the cost. Much of the excess cost of the bedside method can be attributed to the high costs of quality control and quality assurance, training, and documentation. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV CLIN LABS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NURSING,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 12 TC 39 Z9 39 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD SEP PY 1994 VL 97 IS 3 BP 222 EP 230 DI 10.1016/0002-9343(94)90004-3 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA PG635 UT WOS:A1994PG63500006 PM 8092170 ER PT J AU SKINNER, MW KETTEN, DR VANNIER, MW GATES, GA YOFFIE, RL KALENDER, WA AF SKINNER, MW KETTEN, DR VANNIER, MW GATES, GA YOFFIE, RL KALENDER, WA TI DETERMINATION OF THE POSITION OF NUCLEUS COCHLEAR IMPLANT ELECTRODES IN THE INNER-EAR SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article ID 3-DIMENSIONAL RECONSTRUCTION; TEMPORAL BONE; LENGTH AB Accurate determination of intracochlear electrode position in patients with cochlear implants could provide a basis for detecting migration of the implant and could aid in the selection of stimulation parameters for sound processor programming. New computer algorithms for submillimeter resolution and 3-D reconstruction from spiral computed tomographic (CT) scans now make it possible to accurately determine the position of implanted electrodes within the cochlear canal. The accuracy of these algorithms was tested using an electrode array placed in a phantom model. Measurements of electrode length and interelectrode distance from spiral CT scan reconstructions were in close agreement with those stereo microscopy. Although apparent electrode width was increased on CT scans due to partial volume averaging, a correction factor was developed for measurements from conventional radiographs and an expanded CT absorption value scale added to detect the presence of platinum electrodes and wires. The length of the cochlear canal was calculated from preoperative spiral CT scans for one patient, and the length of insertion of the electrode array was calculated from her postoperative spiral CT scans. The cross-sectional position of electrodes in relation to the outer bony wall and modiolus was measured and plotted as a function of distance with the electrode width correction applied. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02114. SIEMENS AG,BEREICH MED TECH,W-8520 ERLANGEN,GERMANY. WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT INST RADIOL,DEPT RADIOL,ST LOUIS,MO 63110. UNIV WASHINGTON,DEPT OTOLARYNGOL HEAD & NECK SURG,SEATTLE,WA 98195. RP SKINNER, MW (reprint author), WASHINGTON UNIV,SCH MED,DEPT OTOLARYNGOL HEAD & NECK SURG,517 S EUCLID AVE,CAMPUS BOX 8115,ST LOUIS,MO 63110, USA. OI Vannier, Michael/0000-0001-9898-384X FU NIDCD NIH HHS [5P01-DC00361-06A1, R01-DC00581] NR 20 TC 55 Z9 61 U1 0 U2 1 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 1994 VL 15 IS 5 BP 644 EP 651 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA PG167 UT WOS:A1994PG16700011 PM 8572066 ER PT J AU MILLER, JW ADAMIS, AP SHIMA, DT DAMORE, PA MOULTON, RS OREILLY, MS FOLKMAN, J DVORAK, HF BROWN, LF BERSE, B YEO, TK YEO, KT AF MILLER, JW ADAMIS, AP SHIMA, DT DAMORE, PA MOULTON, RS OREILLY, MS FOLKMAN, J DVORAK, HF BROWN, LF BERSE, B YEO, TK YEO, KT TI VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITY FACTOR IS TEMPORALLY AND SPATIALLY CORRELATED WITH OCULAR ANGIOGENESIS IN A PRIMATE MODEL SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MINIATURE PIGS; VASOPROLIFERATIVE MICROANGIOPATHY; VEIN OCCLUSION; TISSUE HYPOXIA; TUMOR; CELLS; NEOVASCULARIZATION; EXPRESSION; INHIBITION; MITOGEN AB Ischemia often precedes neovascularization. In ocular neovascularization, such as occurs in diabetic retinopathy, a diffusible angiogenic factor has been postulated to be produced by ischemic retina and to lead to neovascularization of the retina, optic nerve, or iris. However, no angiogenic factor has been conclusively identified that satisfies this hypothesis. Vascular endothelial growth factor/vascular permeability factor, hereafter referred to as VEGF, is a likely candidate for an ocular angiogenic factor because it is a secreted mitogen, specific for endothelial cells, and is upregulated by hypoxia. We investigated the association of VEGF with the development of experimental iris neovascularization in the cynomolgus monkey. Following ther production of retinal ischemia by laser occlusion of all branch retinal veins, VEGF was increased in the aqueous fluid, and the aqueous VEGF levels changed synchronously and proportionally with the severity of iris neovascularization. Northern analysis and in situ hybridization revealed that VEGF messenger RNA is upregulated in the ischemic retina. These observations support the hypothesis that ocular neovascularization is regulated by a diffusible factor and identify VEGF as a likely candidate for a retina-derived vascular permeability and angiogenesis factor in vivo. C1 CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. RP MILLER, JW (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 40624]; NEI NIH HHS [NEI EY 00325, NEI EY 05985] NR 37 TC 522 Z9 546 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD SEP PY 1994 VL 145 IS 3 BP 574 EP 584 PG 11 WC Pathology SC Pathology GA PG110 UT WOS:A1994PG11000011 PM 7521577 ER PT J AU BARNES, JL HASTINGS, RR DELAGARZA, MA AF BARNES, JL HASTINGS, RR DELAGARZA, MA TI SEQUENTIAL EXPRESSION OF CELLULAR FIBRONECTIN BY PLATELETS, MACROPHAGES, AND MESANGIAL CELLS IN PROLIFERATIVE GLOMERULONEPHRITIS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HABU SNAKE-VENOM; SMOOTH-MUSCLE ACTIN; GROWTH-FACTOR-BETA; EXTRACELLULAR-MATRIX; GENE-EXPRESSION; GLOMERULAR-DISEASES; HUMAN-KIDNEY; RAT; LOCALIZATION; RECEPTORS AB Fibronectin (Fn) regulates cell migration, proliferation, and extracellular matrix formation during embryogenesis, angiogenesis, and wound healing. Fn also promotes mesangial cell migration and proliferation in vitro and contributes to extracellular matrix formation and tissue remodeling during glomerular disease. In this study, we examined, by immunohistochemistry and in situ hybridization, the temporal glomerular localization and cellular sources of Fn in Habu snake venom (HSV)-induced proliferative glomerulonephritis. Early HSV-induced glomerular lesions consisted of microaneurysms devoid of resident glomerular cells and filled with platelets, leukocytes, and erythrocytes. Over the course of the disease, mesangial cells migrated into the lesions, proliferated, and formed a confluent cellular mass. Fn was present in lesions beginning at 8 hours, with highest intensity at 72 hours and diminishing at 2 weeks after HSV. Staining for Fn at 8 and 24 hours after HSV was attributed to platelets and macrophages. In situ hybridization and phenotypic identification of cell types within lesions revealed macrophages as the predominant source of cellular Fn mRNA at these times. At 48 hours after HSV, Fn mRNA was expressed in proliferating mesangial cells in addition to macrophages. Most cells in lesions at 72 hours after HSV were mesangial, at a time when expression of Fn mRNA peaked. Cellular expression for Fn mRNA and translated protein declined at 2 weeks after HSV. These studies support the hypothesis that Fn, derived from platelets and macrophages, provides a provisional matrix involved with mesangial cell migration into glomerular lesions. Fn produced by mesangial cells might contribute to the formation of a stable extracellular matrix. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP BARNES, JL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEPHROL,7703 FLOYD DR,SAN ANTONIO,TX 78284, USA. FU NIDDK NIH HHS [DK38758] NR 56 TC 57 Z9 58 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 1994 VL 145 IS 3 BP 585 EP 597 PG 13 WC Pathology SC Pathology GA PG110 UT WOS:A1994PG11000012 PM 8080041 ER PT J AU LIN, CM MUSCH, M MEO, P ZEBROWITZ, J CHANG, E KLEYMAN, TR AF LIN, CM MUSCH, M MEO, P ZEBROWITZ, J CHANG, E KLEYMAN, TR TI ANTIIDIOTYPIC ANTIBODIES TO DELINEATE EPITOPE SPECIFICITY OF ANTI-AMILORIDE ANTIBODIES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE MONOCLONAL ANTIBODIES; SODIUM ION/HYDROGEN ION EXCHANGE ID DISTINCT EPITOPES; NA+ CHANNELS; RECEPTOR; ANALOG AB Amiloride and related compounds have found widespread use as cation transport inhibitors. We have previously raised a series of polyclonal anti-amiloride antibodies using different amiloride-protein conjugates as immunogens, where amiloride was coupled to protein either through its guanidino moiety or through its 5-aminopyrazinyl moiety. The anti-amiloride antibodies recognized distinct sites on amiloride, and the site of attachment of amiloride to carrier protein was a critical factor in determining which part of the amiloride molecule was recognized by the anti-amiloride antibody. The specificity of binding of amiloride analogues to these polyclonal anti-amiloride antibodies mimicked the specificity of binding of amiloride analogues to selected isoforms of the epithelial Na+ channel or the Na+/H+ exchanger, suggesting that antigen binding site of these antibodies might be similar in structure to amiloride binding sites on selected Nai transport proteins. We previously generated monoclonal antiidiotypic antibodies RA2.4 and RA6.3 by an auto-anti-idiotypic approach, using amiloride coupled to albumin through the guanidinium moiety (amiloride-A1). We have now raised a series of monoclonal anti-idiotypic antibodies, T6, T26, T40, and T181, using amiloride coupled to keyhole limpet hemocyanin through the 5-aminopyrazinyl moiety (amiloride-A5) as an immunogen with the same auto-anti-idiotypic approach. These monoclonal anti-idiotypic antibodies recognized both polyclonal anti-amiloride-Al and anti-amiloride-A5 antibodies, suggesting that idiotype-anti-idiotype interaction was not epitope restricted. Competitive inhibition studies demonstrated that the binding of monoclonal antibodies T6 and T40 to the anti-amiloride-A5 antibody is inhibited by amiloride and 5-(N-ethyl-N-isopropyl)amiloride, suggesting that T6 and T40 bind at or near the amiloride binding site of the anti-amiloride-A5 antibody. The monoclonal antibody T6 inhibited Na+/H+ exchange activity of the brush border of chicken enterocytes by 19%, suggesting that this antibody might interact with the amiloride binding site on the Na+/H+ exchanger. C1 UNIV PENN,VET AFFAIRS MED CTR,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,VET AFFAIRS MED CTR,DEPT PHYSIOL,PHILADELPHIA,PA 19104. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. FU NIDDK NIH HHS [DK-42086, DK-38510] NR 16 TC 3 Z9 3 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1994 VL 267 IS 3 BP C821 EP C826 PN 1 PG 6 WC Physiology SC Physiology GA PH382 UT WOS:A1994PH38200019 PM 7524337 ER PT J AU VALENTI, G VERBAVATZ, JM SABOLIC, I AUSIELLO, DA VERKMAN, AS BROWN, D AF VALENTI, G VERBAVATZ, JM SABOLIC, I AUSIELLO, DA VERKMAN, AS BROWN, D TI A BASOLATERAL CHIP28/MIP26-RELATED PROTEIN (BLIP) IN KIDNEY PRINCIPAL CELLS AND GASTRIC PARIETAL-CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE COLLECTING DUCT; WATER CHANNELS; BASOLATERAL PLASMA MEMBRANE; IMMUNOCYTOCHEMISTRY; BASOLATERAL INTEGRAL PROTEIN ID CHIP28 WATER-CHANNEL; INTEGRAL MEMBRANE-PROTEIN; CORTICAL COLLECTING DUCT; ORTHOGONAL ARRAYS; RAT-KIDNEY; APICAL MEMBRANE; AQUAPORIN CHIP; TUBULE; EXPRESSION; RECONSTITUTION AB The water channel CHIP28 accounts for the high water permeability of proximal tubules and thin descending limbs of Henle; a homologous water channel, WCH-CD, in the apical membrane of collecting duct principal cells, may be the vasopressin-sensitive water channel. We show here that one antiserum, raised against CHIP28, immunostains the basolateral membrane of collecting duct principal cells, in addition to staining CHIP28 in other cells. This serum was named anti-basolateral integral protein (anti-BLIP) to distinguish it from other anti-CHIP28 antisera. By Western blotting, BLIP serum recognized both CHIP28 and MIP26, and it stained lens fibers, which contain MIP26 but not CHIP28. BLIP antiserum immunoprecipitated a 28-kDa band, a broad 35- to 50-kDa band, and an similar to 16-kDa band from kidney papilla. It also stained the basolateral membrane of gastric parietal cells, which were not stained with anti-CHIP28 or anti-MIP26 antibodies. BLIP antiserum immunoprecipitated a 28-kDa protein band from stomach; this protein was not precipitated by anti-CHIP28 antibodies. These results suggest that basolateral membranes of principal cells and parietal cells contain a protein(s) that shares common epitopes with CHIP28 and MIP26. Finally, BLIP but not CHIP28 antiserum stained mesothelial (but not epithelial) cells of toad urinary bladder, a further indication that the BLIP antiserum recognizes a protein distinct from CHIP28. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,CANC RES INST,DEPT PHYSIOL & MED,SAN FRANCISCO,CA 94143. FU NIDDK NIH HHS [DK-38452] NR 33 TC 22 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1994 VL 267 IS 3 BP C812 EP C820 PN 1 PG 9 WC Physiology SC Physiology GA PH382 UT WOS:A1994PH38200018 PM 7524336 ER PT J AU INOGUCHI, T XIA, P KUNISAKI, M HIGASHI, S FEENER, EP KING, GL AF INOGUCHI, T XIA, P KUNISAKI, M HIGASHI, S FEENER, EP KING, GL TI INSULINS EFFECT ON PROTEIN-KINASE-C AND DIACYLGLYCEROL INDUCED BY DIABETES AND GLUCOSE IN VASCULAR TISSUES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE HYPERGLYCEMIA; VASCULAR COMPLICATIONS ID HUMAN-ENDOTHELIAL-CELLS; PANCREATIC-ISLETS; DENOVO; COMPLICATIONS; ACCUMULATION; RATS; GLUCOSE-6-PHOSPHATE; PHOSPHOLIPIDS; PATHOGENESIS; GENERATION AB We have reported that membranous protein kinase C (PKC) activities and total diacylglycerol (DAG) levels are increased in the heart and aorta of diabetic rats, which cannot be easily reversed by euglycemic control. However, insulin treatment, which achieved euglycemia, can prevent the increase in PKC activities and DAG levels. Chronic exposure to elevated glucose levels (5.5 vs. 22 mM) increased DAG levels in cultured bovine and rat aortic endothelial cells and smooth muscle cells by 31, 140, and 143%, respectively, only after 3 days of incubation. Glyceraldehyde, which can stimulate the de novo synthesis of DAG, significantly increased DAG levels by 7.1 +/- 0.6-fold after only 16 h of incubation. Elevated glucose levels did not affect labeled DAG when all of the vascular cells were incubated with [H-3]arachidonate, [H-3]glycerol, or [H-3]phosphatidylcholine, whereas [H-3]palmitate- and [(3)Hloleic acid-labeled DAG levels were significantly increased, indicating that the glucose-stimulated increase in DAG is derived partially from the de novo synthesis pathway. Immunoblotting studies showed increases only in PKC isoform beta II but not alpha in aortic smooth muscle cells. The phosphorylation level of MARCKS protein, an intracellular substrate of PKC, was also increased, consistent with the PKC activity increase. These findings showed that diabetic and hyperglycemia-induced increases in PKC activity and DAG levels in the heart and aorta are preventable by insulin treatment. C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. RI Xia, Pu/G-3090-2010 OI Xia, Pu/0000-0003-4705-8878 FU NEI NIH HHS [EY-05110]; NIDDK NIH HHS [DK-36836, P30 DK036836] NR 34 TC 134 Z9 136 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1994 VL 267 IS 3 BP E369 EP E379 PN 1 PG 11 WC Physiology SC Physiology GA PH382 UT WOS:A1994PH38200028 PM 7943217 ER PT J AU SOHN, UD KIM, DK BONVENTRE, JV BEHAR, J BIANCANI, P AF SOHN, UD KIM, DK BONVENTRE, JV BEHAR, J BIANCANI, P TI ROLE OF 100-KDA CYTOSOLIC PLA(2) IN ACH-INDUCED CONTRACTION OF CAT ESOPHAGEAL CIRCULAR MUSCLE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE LOWER ESOPHAGEAL SPHINCTER; ESOPHAGUS; SMOOTH MUSCLE; MUSCLE CONTRACTION; 2ND MESSENGER SYSTEMS; PROTEIN KINASE C; DIACYLGLYCEROL; CALCIUM; ACETYLCHOLINE; PHOSPHOLIPASE C; PHOSPHOLIPASE D; PHOSPHATIDYLINOSITOL; PHOSPHATIDYLCHOLINE; CYTOSOLIC PHOSPHOLIPASE A(2); SECRETORY PHOSPHOLIPASE A(2); ANIMAL; CATS ID PROTEIN-KINASE-C; ARACHIDONIC-ACID-RELEASE; SIGNAL TRANSDUCTION; PHOSPHATIDYLCHOLINE HYDROLYSIS; PROSTAGLANDIN-E2 PRODUCTION; PLATELET PHOSPHOLIPASE-A2; PERITONEAL-MACROPHAGES; MESANGIAL CELLS; ACTIVATION; PURIFICATION AB We have shown that acetyl choline (ACh)-induced contraction of esophageal circular muscle cells is mediated by activation of protein kinase C (PKC). We now examine the role of phospholipase A(2) (PLA(2)). ACh increases [H-3]arachidonic acid release in esophageal but not in lower esophageal sphincter (LES) muscle. In addition, ACh-induced contraction of esophageal but not of LES cells was reduced by the PLA(2) antagonist dimethyleicosadienoic acid and by antiserum to a 100-kDa cytosolic PLA(2) (cPLA(2)). These data suggest that the 100-kDa cPLA(2) plays a role in ACh-induced contraction of esophageal but not of LES muscle. In esophageal cells, arachidonic acid produced by PLA(2) caused little contraction by itself but potentiated contraction induced by the PKC agonist diacylglycerol (DAG). The free fatty acids linoleic acid and linolenic acid also potentiated DAG-induced contraction. Indomethacin and nordihydroguaiaretic acid had no effect on arachidonic acid-induced potentiation of DAG. The potentiation of DAG-induced contraction by arachidonic acid was inhibited by the PKC inhibitor H-7, but it was not affected by the calmodulin inhibitor CGS-9343B. We conclude that a 100-kDa cPLA(2) participates in ACh-induced esophageal contraction by producing arachidonic acid and potentiating DAG-induced activation of a PKC-dependent pathway. C1 BROWN UNIV,RHODE ISL HOSP,GI MOTIL RES LAB,SWP5,PROVIDENCE,RI 02903. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. HARVARD UNIV,BOSTON,MA 02129. FU NIDDK NIH HHS [R01-DK-28614, DK-39773, DK-38452] NR 56 TC 25 Z9 25 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD SEP PY 1994 VL 267 IS 3 BP G433 EP G441 PN 1 PG 9 WC Physiology SC Physiology GA PH382 UT WOS:A1994PH38200055 PM 7943241 ER PT J AU SAXE, GN CHINMAN, G BERKOWITZ, R HALL, K LIEBERG, G SCHWARTZ, J VANDERKOLK, BA AF SAXE, GN CHINMAN, G BERKOWITZ, R HALL, K LIEBERG, G SCHWARTZ, J VANDERKOLK, BA TI SOMATIZATION IN PATIENTS WITH DISSOCIATIVE DISORDERS SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MULTIPLE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; CHRONIC PELVIC PAIN; URINARY NOREPINEPHRINE; HYSTERIA; VALIDITY; INTERVIEW; ELEVATION; SYMPTOMS; WOMEN AB Objective: This study attempted to determine the prevalence of somatic symptoms, somatization disorder, and medical interventions in patients with dissociative disorders. Method: Fourteen psychiatric inpatients with a DSM-III dissociative disorder were matched for age and gender with a comparison group of inpatients who reported few dissociative symptoms. All subjects were interviewed in a blind manner with the Dissociative Disorders Interview Schedule (this semistructured interview schedule includes a section on somatization disorder), and their hospital charts were reviewed to determine somatic symptoms and medical histories. Results: Sixty-four percent of the patients with dissociative disorders met DSM-III criteria for somatization disorder and reported an average of 12.4 somatic symptoms. None of the comparison patients met DSM-III criteria for somatization disorder, and these patients reported an average of 3.1 somatic symptoms. These differences between the two groups were significant. Significant differences were also found in the number of medical hospitalizations and consultations between the two groups. A significant correlation was found between the degree of dissociation and degree of somatization in patients with dissociative disorders. Conclusions: The authors conclude that somatization disorder is a frequent and serious comorbid disorder among patients with dissociative disorders. C1 HARVARD UNIV,SCH MED,TRAUMA CLIN,BOSTON,MA. MASSACHUSETTS MENTAL HLTH CTR,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 56 TC 107 Z9 108 U1 2 U2 7 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 1994 VL 151 IS 9 BP 1329 EP 1334 PG 6 WC Psychiatry SC Psychiatry GA PE366 UT WOS:A1994PE36600015 PM 8067489 ER PT J AU FAVA, M ROSENBAUM, JF MCGRATH, PJ STEWART, JW AMSTERDAM, JD QUITKIN, FM AF FAVA, M ROSENBAUM, JF MCGRATH, PJ STEWART, JW AMSTERDAM, JD QUITKIN, FM TI LITHIUM AND TRICYCLIC AUGMENTATION OF FLUOXETINE TREATMENT FOR RESISTANT MAJOR DEPRESSION - A DOUBLE-BLIND, CONTROLLED-STUDY SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note AB Forty-one patients who had failed to respond to 8 weeks of treatment with 20 mg of fluoxetine were randomly assigned to one of three treatments for 4 weeks: 40-60 mg/day of fluoxetine, 20 mg/day of fluoxetine plus 25-50 mg/day of desipramine, and 20 mg/day of fluoxetine plus 300-600 mg/day of lithium. Patients treated with high-dose fluoxetine (N=15) did significantly better than patients treated with fluoxetine plus lithium (N=14) and those treated with fluoxetine plus desipramine (N=12). High-dose fluoxetine was the most effective treatment among partial responders to previous treatment, but high-dose fluoxetine and fluoxetine plus lithium were the most effective treatments among nonresponders. C1 COLUMBIA UNIV,NEW YORK STATE PSYCHIAT INST,NEW YORK,NY. UNIV PENN,MED CTR,DEPRESS RES UNIT,PHILADELPHIA,PA 19104. RP FAVA, M (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,ACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. RI McGrath, Patrick/I-6410-2013 OI McGrath, Patrick/0000-0001-7217-7321 NR 10 TC 171 Z9 175 U1 0 U2 0 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 1994 VL 151 IS 9 BP 1372 EP 1374 PG 3 WC Psychiatry SC Psychiatry GA PE366 UT WOS:A1994PE36600022 PM 8067495 ER PT J AU ACKMAN, JB WHITMAN, GJ CHEW, FS AF ACKMAN, JB WHITMAN, GJ CHEW, FS TI AGGRESSIVE FIBROMATOSIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note ID DESMOID TUMORS C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 6 TC 10 Z9 10 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1994 VL 163 IS 3 BP 544 EP 544 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PF504 UT WOS:A1994PF50400010 PM 8079840 ER PT J AU MUELLER, PR AF MUELLER, PR TI DIFFERENTIATING SUBPULMONIC FROM SUBPHRENIC COLLECTIONS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter RP MUELLER, PR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA, USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD SEP PY 1994 VL 163 IS 3 BP 739 EP 740 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PF504 UT WOS:A1994PF50400059 PM 8079881 ER PT J AU LOCKE, JL AF LOCKE, JL TI PHASES IN THE CHILDS DEVELOPMENT OF LANGUAGE - THE LEARNING THAT LEADS TO HUMAN SPEECH BEGINS IN THE LAST TRIMESTER OF PREGNANCY - LONG BEFORE THEY UTTER A WORD, INFANTS ARE TALKING THEMSELVES INTO A LANGUAGE SO AMERICAN SCIENTIST LA English DT Article C1 MASSACHUSETTS GEN HOSP,NEUROLINGUIST LAB,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP LOCKE, JL (reprint author), MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,GRAD PROGRAM COMMUN SCI & DISORDERS,101 MERRIMAC ST,BOSTON,MA 02114, USA. NR 4 TC 4 Z9 4 U1 0 U2 1 PU SIGMA XI-SCI RES SOC PI RES TRIANGLE PK PA PO BOX 13975, RES TRIANGLE PK, NC 27709 SN 0003-0996 J9 AM SCI JI Am. Scientist PD SEP-OCT PY 1994 VL 82 IS 5 BP 436 EP 445 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PD323 UT WOS:A1994PD32300013 ER PT J AU BEHRINGER, EC BURKE, SM AF BEHRINGER, EC BURKE, SM TI TECHNICAL ERRORS DURING IN-HOSPITAL CARDIOPULMONARY-RESUSCITATION (CPR) SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT PHYSIOL REPROD,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1213 EP A1213 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101212 ER PT J AU BIGATELLO, LM NISHIMURA, M HESS, DR KIMBALL, WR KACMAREK, RM AF BIGATELLO, LM NISHIMURA, M HESS, DR KIMBALL, WR KACMAREK, RM TI PROPORTIONAL VS FIXED UNLOADING OF THE WORK OF BREATHING IN A LUNG MODEL SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RESP CARE,BOSTON,MA 02114. 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A302 EP A302 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100302 ER PT J AU BODY, S PARKS, R LEY, C MADDI, R LEVIN, J STOVER, EP SIEGEL, L SPIESS, B DAMBRA, M AF BODY, S PARKS, R LEY, C MADDI, R LEVIN, J STOVER, EP SIEGEL, L SPIESS, B DAMBRA, M TI EFFICACY OF RE-TRANSFUSION OF SHED MEDIASTINAL BLOOD AFTER CABG SURGERY - A MULTIINSTITUTIONAL ANALYSIS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,DEPT ANESTHESIA,BOSTON,MA 02115. STANFORD UNIV,MED CTR,SCH MED,DEPT ANESTHESIA,STANFORD,CA 94305. UNIV WASHINGTON,DEPT ANESTHESIA,SEATTLE,WA 98195. MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. UCSF,VET ADM MED CTR,DEPT MED LAB,SAN FRANCISCO,CA 94121. MCSPI,SAN FRANCISCO,CA 94134. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1245 EP A1245 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101244 ER PT J AU CROSBY, G MAROTA, JJA ROOT, C ABE, K HUANG, P AF CROSBY, G MAROTA, JJA ROOT, C ABE, K HUANG, P TI NOXIOUS STIMULATION-INDUCED NEUROPLASTICITY IS NOT ALTERED IN TRANSGENIC MICE DEFICIENT IN NEURONAL NITRIC-OXIDE SYNTHASE SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 3 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A803 EP A803 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100802 ER PT J AU DEBROS, F GOUDSOUZIAN, N CHAKRAVORTY, S PATEL, S COOK, DR AF DEBROS, F GOUDSOUZIAN, N CHAKRAVORTY, S PATEL, S COOK, DR TI PHARMACOKINETIC EVALUATION OF THE CIS-CIS ISOMER, ALCOHOL AND ESTER METABOLITES OF MIVACURIUM DURING PROLONGED INFUSIONS IN NEUROSURGICAL PATIENTS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. CHILDRENS HOSP PITTSBURGH,PITTSBURGH,PA 15213. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1085 EP A1085 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101084 ER PT J AU DERSHWITZ, M ROSCOW, CE MICHALOWSKI, P CONNORS, PM HOKE, JF MUIR, KT DIENSTAG, JL AF DERSHWITZ, M ROSCOW, CE MICHALOWSKI, P CONNORS, PM HOKE, JF MUIR, KT DIENSTAG, JL TI PHARMACOKINETICS AND PHARMACODYNAMICS OF REMIFENTANIL IN VOLUNTEER SUBJECTS WITH SEVERE LIVER-DISEASE COMPARED WITH NORMAL SUBJECTS SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 GLAXO RES INST,DEPT CLIN PHARMACOL,RES TRIANGLE PK,NC 27709. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT GASTROENTEROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 4 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A377 EP A377 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100376 ER PT J AU FAHMY, NR AF FAHMY, NR TI A COMPARISON OF 3 METHODS FOR BLOOD CONSERVATION FOR MAJOR ORTHOPEDIC PROCEDURES SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,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 SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A1248 EP A1248 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09101247 ER PT J AU FORMAN, SA MILLER, KW YELLEN, G AF FORMAN, SA MILLER, KW YELLEN, G TI GENERAL ANESTHETIC POTENCY IS UNALTERED BY MUTATIONS IN THE M2 (ION-CHANNEL) DOMAINS OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR THAT MODULATE LOCAL-ANESTHETIC POTENCY SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROBIOL,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A873 EP A873 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100872 ER PT J AU FUKUDA, T KIM, DK HALES, CA BONVENTRE, JV AF FUKUDA, T KIM, DK HALES, CA BONVENTRE, JV TI ENHANCED CYTOSOLIC PHOSPHOLIPASE-A2 ACTIVITY IN LUNGS OF SHEEP AFTER SMOKE-INHALATION INJURY SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 HYOGO MED UNIV,DEPT ANESTHESIOL,NISHINOMIYA,HYOGO 663,JAPAN. MASSACHUSETTS GEN HOSP,DEPT MED,RENAL & PULM UNIT,BOSTON,MA 02114. 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 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1994 VL 81 IS 3A SU S BP A297 EP A297 PG 1 WC Anesthesiology SC Anesthesiology GA PJ091 UT WOS:A1994PJ09100297 ER EF