FN Thomson Reuters Web of Science™ VR 1.0 PT J AU STEC, DE KRIEGER, JE JACOB, HJ ROMAN, RJ AF STEC, DE KRIEGER, JE JACOB, HJ ROMAN, RJ TI CONTRIBUTION OF CYTOCHROME-P4504A TO THE DEVELOPMENT OF HYPERTENSION IN SHR SO FASEB JOURNAL LA English DT Meeting Abstract C1 MED COLL WISCONSIN,DEPT PHYSIOL,MILWAUKEE,WI 53226. MASSACHUSETTS GEN HOSP,CURC,BOSTON,MA 02114. RI Krieger, Jose/C-3117-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A580 EP A580 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19603361 ER PT J AU TAUPIN, JL TIAN, O ELLEDGE, S ANDERSON, P AF TAUPIN, JL TIAN, O ELLEDGE, S ANDERSON, P TI IDENTIFICATION OF CANDIDATE SUBSTRATES FOR TIA-1-MEDIATED CYTOTOXICITY SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. BAYLOR COLL MED,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A206 EP A206 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19601186 ER PT J AU TONER, M RINKES, HMB KARLSSON, JOM TOMPKINS, RG YARMUSH, ML AF TONER, M RINKES, HMB KARLSSON, JOM TOMPKINS, RG YARMUSH, ML TI FREEZE-INDUCED INJURY TO HEPATOCYTES CORRELATES WITH THE EXTENT OF INTRACELLULAR ICE FORMATION SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURNS INST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A409 EP A409 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602364 ER PT J AU WEBER, GF FU, W CANTOR, H AF WEBER, GF FU, W CANTOR, H TI DEFINITION OF A NOVEL SIGNALING PATHWAY COUPLED TO TCR LIGATION BY SUPERANTIGEN THAT IS ASSOCIATED WITH PROGRAMMED CELL-DEATH SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOPATHOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A477 EP A477 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19602760 ER PT J AU WILLIAMS, M VANREMMEN, H RICHARDSON, A AF WILLIAMS, M VANREMMEN, H RICHARDSON, A TI EFFECT OF CULTURING ON GENE-EXPRESSION IN RAT HEPATOCYTES SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,GRECC,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1994 VL 8 IS 4 BP A22 EP A22 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA ND196 UT WOS:A1994ND19600125 ER PT J AU PAL, SK TORRY, D SERTA, R CROWELL, RC SEIBEL, MM COOPER, GM KIESSLING, AA AF PAL, SK TORRY, D SERTA, R CROWELL, RC SEIBEL, MM COOPER, GM KIESSLING, AA TI EXPRESSION AND POTENTIAL FUNCTION OF THE C-MOS PROTOONCOGENE IN HUMAN EGGS SO FERTILITY AND STERILITY LA English DT Article DE C-MOS; HUMAN EGGS; MPF; MATURATION; METAPHASE; C-RAF ID MATURATION-PROMOTING FACTOR; OOCYTE MATURATION; INVITRO FERTILIZATION; MEIOTIC MATURATION; CYCLIN SYNTHESIS; XENOPUS OOCYTES; GERM-CELLS; MEIOSIS-II; PRODUCT; GENE AB Objective: To investigate the expression and possible function of the c-mos proto-oncogene in human eggs. Design: Eggs obtained as discarded material from assisted reproductive technology procedures were analyzed for c-mos messenger RNA by reverse transcriptase-polymerase chain reaction. As an approach to investigating c-mos function, we measured maturation-promoting factor (MPF) activity (histone H1 kinase) in eggs without and with inhibition of protein synthesis. Detection of RNA transcripts of c-raf was included as control. Results: Transcripts of c-mos were detected in small fractions of individual eggs, indicating that e-nos is abundantly transcribed. Inhibition of protein synthesis resulted in loss of MPF, leading to chromatin decondensation and reformation of a nucleus. C-raf maternal messages were also detectable in individual human eggs. Conclusion: The c-mos proto-oncogene is an abundant maternal message in human eggs as in other species. The effects of inhibiting protein synthesis in human eggs are similar to those obtained in mouse and Xenopus eggs, either as a consequence of protein synthesis inhibition or specific ablation of c-mos RNA by injection of anti-sense oligonucleotides. The c-mos gene product is thus likely to play a critical role in human oocyte meiosis by regulating the activity of MPF. C1 HARVARD UNIV,SCH MED,FAULKNER CTR REPROD MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02130. FAULKNER HOSP,BOSTON,MA. FU NCI NIH HHS [T32 CA09031]; NICHD NIH HHS [R01 HD26594]; NIGMS NIH HHS [F32 GM13632] NR 25 TC 33 Z9 33 U1 0 U2 0 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 MAR PY 1994 VL 61 IS 3 BP 496 EP 503 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA MZ475 UT WOS:A1994MZ47500015 PM 8137973 ER PT J AU MILLER, LS BARBAREVECH, C FRIEDMAN, LS AF MILLER, LS BARBAREVECH, C FRIEDMAN, LS TI LESS FREQUENT CAUSES OF LOWER GASTROINTESTINAL-BLEEDING SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID SOLITARY RECTAL ULCER; SYSTEMIC LUPUS-ERYTHEMATOSUS; MESENTERIC VENOUS THROMBOSIS; ARGON-LASER TREATMENT; MECKELS-DIVERTICULUM; VEIN-THROMBOSIS; DIVERSION COLITIS; ISCHEMIC COLITIS; COLONIC VARICES; WEGENERS GRANULOMATOSIS C1 THOMAS JEFFERSON UNIV, DIV GASTROENTEROL & HEPATOL, PHILADELPHIA, PA 19107 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. RP TEMPLE UNIV, HLTH SCI CTR, DEPT GASTROENTEROL, 301 N BROAD ST, PHILADELPHIA, PA 19140 USA. NR 249 TC 47 Z9 48 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8553 EI 1558-1942 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 1994 VL 23 IS 1 BP 21 EP 52 PG 32 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MW160 UT WOS:A1994MW16000003 PM 8132299 ER PT J AU RICHTER, JM AF RICHTER, JM TI OCCULT GASTROINTESTINAL-BLEEDING SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Article ID COLORECTAL-CANCER; HEMOCCULT TEST; BLOOD-LOSS; HEMOQUANT ASSAY; COLON CANCER; SENSITIVITY; PATTERNS; ASPIRIN; HEMOGLOBIN; POPULATION C1 MASSACHUSETTS GEN HOSP,MED SERV,GEN INTERNAL MED UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RICHTER, JM (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,GASTROINTESTINAL UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 66 TC 22 Z9 23 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 1994 VL 23 IS 1 BP 53 EP 66 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MW160 UT WOS:A1994MW16000004 PM 8132300 ER PT J AU FRIEDMAN, LS AF FRIEDMAN, LS TI GASTROINTESTINAL-BLEEDING .2. PREFACE SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material RP FRIEDMAN, LS (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BULFINCH 127,32 FRUIT ST,BOSTON,MA 02114, USA. 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 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 1994 VL 23 IS 1 BP R9 EP R10 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MW160 UT WOS:A1994MW16000001 ER PT J AU DANKO, I FRITZ, JD JIAO, SS HOGAN, K LATENDRESSE, JS WOLFF, JA AF DANKO, I FRITZ, JD JIAO, SS HOGAN, K LATENDRESSE, JS WOLFF, JA TI PHARMACOLOGICAL ENHANCEMENT OF IN-VIVO FOREIGN GENE-EXPRESSION IN MUSCLE SO GENE THERAPY LA English DT Article ID MOUSE SKELETAL-MUSCLE; MUSCULAR-DYSTROPHY; LOCAL-ANESTHETICS; MAMMALIAN-CELLS; PLASMID DNA; LONG-TERM; REGENERATION; INVIVO; RAT; BUPIVACAINE AB Intramuscular injection of naked plasmid DNA provides a means for gene transfer and expression in striated muscle. in this study, the effects oi treating muscle with normal saline, etidocaine, mepivacaine, acetic anhydride, sodium bicarbonate, Notechis scutatus venom, cardiotoxin and bupivacaine before plasmid DNA injection on foreign gene expression were evaluated Dose dependence, strain and species specificity, the time interval between pharmacological agent and plasmid DNA injection, the stability of gene expression and the Tate of the injected plasmid DNA were studied using reporter gene expression, by histological examination and semi-quantitative polymerase chain reaction. Of the various gents tested, the best enhancement of foreign gene expression occurred in muscle treated with 0.75% bupivacaine five to seven days before plasmid DNA injection. Rat and mouse quadriceps muscle treated with 0.75% bupivacaine had levels of luciferase activity four- to 40-times greater than non-bupivacaine-treated muscle. Also, beta-galactosidase expressing myofibers were observed throughout the length of the muscle in samples treated with 0.75% bupivacaine before reporter gene injection. Muscle treated with 0.75% bupivacaine fully recovered from the degeneration caused by its injection with no long-term effects histologically. The heightened level of reporter gene expression persisted in 0.75% bupivacaine-treated muscle for one month, but decreased to that of non-bupivacaine-treated muscle by two months after plasmid DNA injection. Enhancement oi foreign gene expression may be particularly advantageous in vaccination protocols employing intramuscular plasmid injection. C1 UNIV WISCONSIN,WAISMAN CTR,DEPT PEDIAT,MADISON,WI 53705. UNIV WISCONSIN,WAISMAN CTR,DEPT MED GENET,MADISON,WI 53705. UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET ADM HOSP,DEPT ANESTHESIOL,MADISON,WI 53706. UNIV WISCONSIN,CTR CLIN SCI,MADISON,WI 53706. NR 39 TC 136 Z9 148 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 1994 VL 1 IS 2 BP 114 EP 121 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PT946 UT WOS:A1994PT94600006 PM 7584066 ER PT J AU HAMNER, MB AF HAMNER, MB TI EXACERBATION OF POSTTRAUMATIC-STRESS-DISORDER SYMPTOMS WITH MEDICAL ILLNESS SO GENERAL HOSPITAL PSYCHIATRY LA English DT Note ID POST-TRAUMATIC STRESS; KOREAN WAR PRISONERS; FOLLOW-UP; MORTALITY AB Chronic posttraumatic stress disorder (PTSD) may increase the risk for associated psychiatric and medical illnesses. In turn, the onset of medical illness may result in an exacerbation of PTSD symptoms leading to excessive or maladaptive psychological and physiological reactions. Five combat veterans with PTSD and medical disease are presented to illustrate this potential for worsening of PTSD with concurrent medical illness. Health care workers in general hospital settings should be aware of unique psychological vulnerabilities in PTSD patients. Prospective studies are needed to assess the impact of medical comorbidity on the course of PTSD. C1 RALPH HENRY JOHNSON DEPT VET AFFAIRS MED CTR,PSYCHIAT SERV,CHARLESTON,SC. MED UNIV S CAROLINA,DEPT PSYCHIAT & HLTH BEHAV SCI,CHARLESTON,SC 29425. NR 13 TC 15 Z9 15 U1 0 U2 1 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 MAR PY 1994 VL 16 IS 2 BP 135 EP 137 DI 10.1016/0163-8343(94)90058-2 PG 3 WC Psychiatry SC Psychiatry GA NL442 UT WOS:A1994NL44200012 PM 8039692 ER PT J AU NISHIYAMA, M INAZAWA, J ARIYAMA, T NAKAMURA, Y MATSUFUJI, S FURUSAKA, A TANAKA, T HAYASHI, S WANDS, JR AF NISHIYAMA, M INAZAWA, J ARIYAMA, T NAKAMURA, Y MATSUFUJI, S FURUSAKA, A TANAKA, T HAYASHI, S WANDS, JR TI THE HUMAN INSULIN-RECEPTOR SUBSTRATE-1 GENE (IRS1) IS LOCALIZED ON 2Q36 SO GENOMICS LA English DT Note ID CHROMOSOME-1; PROTEIN; SUSCEPTIBILITY; HYBRIDIZATION; ASSIGNMENT; CLONING; MICE C1 JIKEI UNIV,DAISIAN HOSP,SCH MED,DEPT INTERNAL MED,TOKYO,JAPAN. MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. CANC INST,DEPT BIOCHEM,TOKYO,JAPAN. KYOTO PREFECTURAL UNIV MED,DEPT HYG,KYOTO 602,JAPAN. RP NISHIYAMA, M (reprint author), JIKEI UNIV,SCH MED,DEPT NUTR,MINATO KU,TOKYO 105,JAPAN. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-08169, AA-02666] NR 20 TC 6 Z9 6 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 0888-7543 J9 GENOMICS JI Genomics PD MAR 1 PY 1994 VL 20 IS 1 BP 139 EP 141 DI 10.1006/geno.1994.1143 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NB193 UT WOS:A1994NB19300025 PM 8020946 ER PT J AU RUTAN, JS ALONSO, A AF RUTAN, JS ALONSO, A TI SOME GUIDELINES FOR GROUP THERAPISTS SO GROUP LA English DT Article C1 FIELDING INST,SANTA BARBARA,CA. MASSACHUSETTS GEN HOSP,THERAPY GRP,BOSTON,MA 02114. RP RUTAN, JS (reprint author), HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115, USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0362-4021 J9 GROUP JI Group PD SPR PY 1994 VL 18 IS 1 BP 56 EP 69 DI 10.1007/BF01459720 PG 14 WC Psychology, Clinical SC Psychology GA NM101 UT WOS:A1994NM10100007 ER PT J AU MIKAEL, N MIRZA, NM ZAHARIAN, BI DEULOFEUT, H SALAZAR, M YUNIS, EJ DUBEY, DP AF MIKAEL, N MIRZA, NM ZAHARIAN, BI DEULOFEUT, H SALAZAR, M YUNIS, EJ DUBEY, DP TI GENETIC-CONTROL OF THE DECLINE OF NATURAL-KILLER-CELL ACTIVITY IN AGING MICE SO GROWTH DEVELOPMENT AND AGING LA English DT Article DE AGING; CHROMOSOME 4; CONGENIC MICE; IMMUNE FUNCTION; LYRIC UNITS; NK CELLS; NK1.1 ANTIGENS; POLYINOSINIC, POLYCYTIDYLIC ACID; SERINE ESTERASE AND TUMORS ID CYTO-TOXICITY; NK CELLS; AGE; ANTIGEN AB Mt cell activity declines with age and is strain dependent. We investigated the age associated decline of NK cell activity in the HW26C strain of mice. The bilineal congenic strain HW26C which contains a segment of chromosome 4 of BALB/cBy introduced onto the C57BL/6By (B6) background was used to investigate the decline of NK cell activity with age. Our experiments showed that there is a significant decline of NK cell activity in old (18-26 months) HW26C mice as compared to the B6. By contrast, the NK cell frequency determined using a surface marker for NK cells, NK1.1, did not show any significant difference with age. It appears therefore, that the decline in NK activity during aging is a reflection of loss of lytic activity rather than an actual decline in the number of NK cells and the responsible gene(s) resides in chromosome 4. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [NIA CA06516-29]; NIA NIH HHS [NIA AG02329]; NIAID NIH HHS [NIA AI26817] NR 28 TC 7 Z9 7 U1 0 U2 0 PU GROWTH PUBL CO INC PI BAR HARBOR PA PO BOX 42, BAR HARBOR, ME 04609-0042 SN 0017-4793 J9 GROWTH DEVELOP AGING JI Growth Dev. Aging PD SPR PY 1994 VL 58 IS 1 BP 3 EP 12 PG 10 WC Developmental Biology; Geriatrics & Gerontology SC Developmental Biology; Geriatrics & Gerontology GA NL426 UT WOS:A1994NL42600001 PM 8077079 ER PT J AU BADIMON, L MEYER, BJ BADIMON, JJ AF BADIMON, L MEYER, BJ BADIMON, JJ TI THROMBIN IN ARTERIAL THROMBOSIS SO HAEMOSTASIS LA English DT Article; Proceedings Paper CT 13th International Congress on Thrombosis CY JUN 06-10, 1994 CL BILBAO, SPAIN DE THROMBIN; ARTERIAL THROMBOSIS; HIRUDIN; HEPARIN; R-HIRUDIN; HIRULOG ID VESSEL WALL; HEPARIN; HIRUDIN; THROMBOLYSIS; ANGIOPLASTY; MODEL; ANTITHROMBIN; MECHANISMS; EXPRESSION; INHIBITION AB Thrombin plays a pivotal role in the pathogenesis of arterial thrombosis. Platelet-rich thrombosis after arterial injury is dependent on the depth and extent of injury, local rheological conditions and the persistence of residual mural thrombus. The unique effects of specific thrombin inhibitors, including thrombin action on platelets and blood coagulation, demonstrated in experimental and preliminary clinical trials, suggest that specific thrombin inhibitors may be the next major advance in antithrombotic therapy of acute coronary syndromes. The importance of thrombin lies not just in acute thrombus formation following arterial injury but thrombin also contributes to smooth muscle cell proliferation by stimulating platelet secretion of growth factors (especially platelet derived growth factor, PDGF) and directly acting on smooth muscle cells. Thus, thrombin has direct effects on cell proliferation and influences the cellular synthetic mechanisms responsible for matrix protein and collagen production. The role for thrombin as a possible mitogen for vascular cells has gained support by the identification of a cellular thrombin receptor and by the recent detection of m-RNA for this receptor in human atherosclerotic plaques. Therefore, specific thrombin inhibition may also have a potential impact on the relative proliferative response of endothelial and smooth muscle cells after arterial injury such as PTCA by preventing restenosis. C1 HOSP SANTA CRUZ & SAN PABLO,CARDIOVASC RES CTR,BARCELONA,SPAIN. HOSP SANTA CRUZ & SAN PABLO,CSIC,FDN CID,BARCELONA,SPAIN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 33 TC 39 Z9 39 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0147 J9 HAEMOSTASIS JI Haemostasis PD MAR-APR PY 1994 VL 24 IS 2 BP 69 EP 80 PG 12 WC Hematology SC Hematology GA NZ870 UT WOS:A1994NZ87000003 PM 7959365 ER PT J AU SPENCER, T BIEDERMAN, J WILENS, T FARAONE, SV AF SPENCER, T BIEDERMAN, J WILENS, T FARAONE, SV TI IS ATTENTION-DEFICIT HYPERACTIVITY DISORDER IN ADULTS A VALID DISORDER SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID MINIMAL BRAIN-DYSFUNCTION; FOLLOW-UP; PSYCHIATRIC STATUS; CHILDHOOD HYPERACTIVITY; LEARNING-DISABILITIES; FAMILIAL ASSOCIATION; RESEARCH CRITERIA; CONDUCT DISORDER; RESIDUAL TYPE; RISK-FACTORS AB Concerns have been raised regarding the validity of the diagnosis of attention-deficit hyperactivity disorder in adults. The Purpose of this report is to evaluate critically whether this diagnosis in adults meets acceptable standards for diagnostic validity. A systematic search was conducted of the psychiatric and psychological literature for empirical studies dealing with adult attention-deficit hyperactivity disorder with childhood onset. These studies were examined for evidence of descriptive, predictive, and concurrent validity. The literature shows that this disorder can be reliably diagnosed in adults and that the diagnosis confers considerable power to forecast complications and treatment response. In addition, evidence is mounting for genetic transmission, specific treatment responses, and abnormalities in brain structure and function in affected individuals. Evidence from the literature is increasingly pointing to the validity of adult attention-deficit hyperactivity disorder. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. VET ADM MED CTR,PSYCHIAT SERV,BROCKTON,MA 02401. RP SPENCER, T (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIATR PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 88 TC 92 Z9 94 U1 1 U2 2 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 MAR-APR PY 1994 VL 1 IS 6 BP 326 EP 335 DI 10.3109/10673229409017099 PG 10 WC Psychiatry SC Psychiatry GA ND907 UT WOS:A1994ND90700004 PM 9384867 ER PT J AU MINICHIELLO, WE OSULLIVAN, RL OSGOODHYNES, D BAER, L AF MINICHIELLO, WE OSULLIVAN, RL OSGOODHYNES, D BAER, L TI TRICHOTILLOMANIA - CLINICAL ASPECTS AND TREATMENT STRATEGIES SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; BEHAVIORAL TREATMENT; HABIT-REVERSAL; CHILDHOOD TRICHOTILLOMANIA; NARCOTIC-ANTAGONISTS; FLUOXETINE TREATMENT; NERVOUS HABITS; ACRAL LICK; HAIR; CLOMIPRAMINE AB Trichotillomania is a disorder of compulsive hair pulling that often results in alopecia. The clinical features include the pulling of hair from the scalp, eyebrows, and eyelashes, sometimes symmetrically; pubic and other bodily hair may also be plucked. The disorder is present in 0.6% of college students. The majority of sufferers who seek treatment are female, with usual age of onset between 11 and 16 years. Trichotillomania can occur in a wide variety of psychiatric disorders, and patients with the condition may be more likely to have a lifetime diagnosis of depression or an anxiety, eating, or substance abuse disorder. Although empirically derived treatment guidelines are still lacking, the current literature suggests that behavior therapy and pharmacotherapy are the most efficacious treatments for adult trichotillomania. Controlled trials with pharmocotherapy (clomipramine) have shown significant reductions in hair pulling over the short term. Controlled investigations of behavior therapy hove not been conducted, but several treatment series suggest efficacy. At least three reports also suggest that behavior therapy and pharmacotherapy bring some improvement in childhood trichotillomania, although this has not been empirically studied. A case illustrating the combination of behavior therapy techniques and pharmacotherapy in the treatment of trichotillomania is presented. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP MINICHIELLO, WE (reprint author), MASSACHUSETTS GEN HOSP,OBSESS COMPULS DISORDERS CLIN,BEHAV THERAPY UNIT,BOSTON,MA 02114, USA. NR 87 TC 21 Z9 22 U1 0 U2 2 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 MAR-APR PY 1994 VL 1 IS 6 BP 336 EP 344 DI 10.3109/10673229409017100 PG 9 WC Psychiatry SC Psychiatry GA ND907 UT WOS:A1994ND90700005 PM 9384868 ER PT J AU SCHOUTEN, R AF SCHOUTEN, R TI ALLEGATIONS OF SEXUAL ABUSE - A NEW AREA OF LIABILITY RISK SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article RP SCHOUTEN, R (reprint author), MASSACHUSETTS GEN HOSP,LAW & PSYCHIAT SERV,BOSTON,MA 02114, USA. NR 5 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 1994 VL 1 IS 6 BP 350 EP 352 DI 10.3109/10673229409017102 PG 3 WC Psychiatry SC Psychiatry GA ND907 UT WOS:A1994ND90700007 PM 9384870 ER PT J AU COHEN, LS ROSENBAUM, JF AF COHEN, LS ROSENBAUM, JF TI HORMONAL THERAPIES FOR PSYCHIATRIC-SYMPTOMS IN WOMEN - POSSIBILITIES AND CAUTIONS SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID PREMENSTRUAL-SYNDROME; DOUBLE-BLIND; CROSSOVER RP COHEN, LS (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,PERINATAL PSYCHIAT RES PROGRAM,BOSTON,MA 02114, USA. NR 15 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 MAR-APR PY 1994 VL 1 IS 6 BP 353 EP 355 DI 10.3109/10673229409017103 PG 3 WC Psychiatry SC Psychiatry GA ND907 UT WOS:A1994ND90700008 PM 9384871 ER PT J AU BLUMENTHAL, D AF BLUMENTHAL, D TI THE VITAL ROLE OF PROFESSIONALISM IN HEALTH-CARE REFORM SO HEALTH AFFAIRS LA English DT Note RP BLUMENTHAL, D (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114, USA. NR 5 TC 26 Z9 26 U1 0 U2 1 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SPR PY 1994 VL 13 IS 1 BP 252 EP 256 DI 10.1377/hlthaff.13.1.252 PG 5 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA MX788 UT WOS:A1994MX78800027 PM 8188143 ER PT J AU MEYER, GS EDWARDS, JN BLUMENTHAL, D AF MEYER, GS EDWARDS, JN BLUMENTHAL, D TI EXPERIENCE OF THE ROBERT-WOOD-JOHNSON HEALTH-POLICY FELLOWSHIP SO HEALTH AFFAIRS LA English DT Article C1 MASSACHUSETTS RATE SETTING COMMISS,BUR AMBULATORY CARE,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114. RP MEYER, GS (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SPR PY 1994 VL 13 IS 2 BP 264 EP 270 DI 10.1377/hlthaff.13.2.264 PG 7 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA NL934 UT WOS:A1994NL93400024 PM 8056380 ER PT J AU CHUNG, RT AF CHUNG, RT TI JUST SAY NO TO VIRAL-HEPATITIS SO HEPATOLOGY LA English DT Note ID NITRIC-OXIDE SYNTHASE; VACCINIA VIRUS; RIBONUCLEOTIDE REDUCTASE; INTERFERON SYSTEM; PROTEIN-KINASE; CELLS; MACROPHAGES; INHIBITION; ARGINASE; PRODUCT RP CHUNG, RT (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. NR 24 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 1994 VL 19 IS 3 BP 790 EP 792 DI 10.1002/hep.1840190337 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MY449 UT WOS:A1994MY44900036 PM 7509773 ER PT J AU HAASE, VH TROFATTER, JA MACCOLLIN, M TARTTELIN, E GUSELLA, JF RAMESH, V AF HAASE, VH TROFATTER, JA MACCOLLIN, M TARTTELIN, E GUSELLA, JF RAMESH, V TI THE MURINE NF2 HOMOLOG ENCODES A HIGHLY CONSERVED MERLIN PROTEIN WITH ALTERNATIVE FORMS SO HUMAN MOLECULAR GENETICS LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; CHROMOSOME-22; TYPE-2; SCHWANNOMAS; DELETIONS; NEUROMAS; DISEASE; LINKAGE; MARKERS; GENES AB The recently isolated gene for neurofibromatosis type 2 (NF2) encodes a 595 amino acid protein, named merlin, which is related to the cytoskeleton-associated proteins moesin, ezrin and radixin. To identify evolutionarily conserved regions and to provide sequence information necessary for the establishment of a mouse model for NF2, we have determined the cDNA sequence of the mouse NF2 tumor suppressor gene, and mapped it in the mouse genome. Mouse merlin is a 596 amino acid protein, 98% identical to human merlin, but one amino acid longer due to the insertion of a proline residue near the C-terminus. Of the nine amino acid differences between mouse and humans, seven occur in the C-terminal 20% of the protein, far from the protein 4.1 domain that defines this family. Two of the NF2 cDNA clones reveal evidence of alternative splicing events that alter the predicted merlin product, one removing a 45 amino acid segment from the middle section of the protein and the other changing the C-terminus. The existence of several different forms of merlin potentially with different primary roles will complicate the identification of the precise function that must be disrupted to cause the NF2-associated tumors. The mouse NF2 homologue maps to Chr 11, in a region homologous to human Chr 22, but devoid of any mouse mutations which could be models of the human disorder. C1 MASSACHUSETTS GEN HOSP EAST,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HGMP,CTR RESOURCE,HARROW HA1 3UJ,MIDDX,ENGLAND. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RI Haase, Volker Hans/A-6758-2013 OI Haase, Volker Hans/0000-0002-7051-8994 FU NHGRI NIH HHS [HG00317]; NINDS NIH HHS [NS24279] NR 26 TC 43 Z9 44 U1 0 U2 4 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 MAR PY 1994 VL 3 IS 3 BP 407 EP 411 DI 10.1093/hmg/3.3.407 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NA583 UT WOS:A1994NA58300003 PM 8012352 ER PT J AU JACOBY, LB MACCOLLIN, M LOUIS, DN MOHNEY, T RUBIO, MP PULASKI, K TROFATTER, JA KLEY, N SEIZINGER, B RAMESH, V GUSELLA, JF AF JACOBY, LB MACCOLLIN, M LOUIS, DN MOHNEY, T RUBIO, MP PULASKI, K TROFATTER, JA KLEY, N SEIZINGER, B RAMESH, V GUSELLA, JF TI EXON SCANNING FOR MUTATION OF THE NF2 GENE IN SCHWANNOMAS SO HUMAN MOLECULAR GENETICS LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; CHROMOSOME-22; TYPE-2; LINKAGE; DELETIONS; NEUROMAS; DISEASE; MARKERS AB Family studies and tumor analyses have combined to indicate that neurofibromatosis 2 (NF2), a disorder characterized by multiple benign tumors of the nervous system, and sporadic non-inherited forms of the same tumor types are both caused by inactivation of a tumor suppressor gene located in 22q12. Recently, the gene encoding merlin, a novel member of a family of cytoskeleton-associated proteins, was identified as the NF2 tumor suppressor. To facilitate the search for merlin mutations, we have defined the exon - intron boundaries for all 17 NF2 exons, including one subject to alternative splicing. We have developed polymerase chain reaction assays to amplify each exon from genomic DNA, and used these assays to perform single-strand conformation polymorphism analysis of DNA from 30 sporadic and eight NF2-derived schwannomas, the hallmark tumor type in this disorder. Of a maximum of 60 alleles scanned, 32 showed mutations affecting expression of the merlin protein. Thirty of these mutations are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal splicing, while two are missense mutations. Thus, inactivation of merlin is a common feature underlying both inherited and sporadic forms of schwannoma. C1 MASSACHUSETTS GEN HOSP EAST,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,MOLEC NEUROONCOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02129. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC GENET & CELL BIOL,ONCOL DRUG DISCOVERY,PRINCETON,NJ 08543. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RI Rubio, Mari-Paz/K-4364-2014 OI Rubio, Mari-Paz/0000-0003-3963-5903 FU NCI NIH HHS [CA51410]; NHGRI NIH HHS [HG00317]; NINDS NIH HHS [NS24279] NR 28 TC 181 Z9 189 U1 0 U2 11 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 MAR PY 1994 VL 3 IS 3 BP 413 EP 419 DI 10.1093/hmg/3.3.413 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NA583 UT WOS:A1994NA58300004 PM 8012353 ER PT J AU OYAMA, T VICKERY, AL PREFFER, FI COLVIN, RB AF OYAMA, T VICKERY, AL PREFFER, FI COLVIN, RB TI A COMPARATIVE-STUDY OF FLOW-CYTOMETRY AND HISTOPATHOLOGIC FINDINGS IN THYROID FOLLICULAR CARCINOMAS AND ADENOMAS SO HUMAN PATHOLOGY LA English DT Article DE THYROID FOLLICULAR CARCINOMAS AND ADENOMAS; CYTOMETRY ID CELLULAR DNA CONTENT; TUMORS; GLAND; NEOPLASMS; STEREOLOGY C1 MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. GUNMA UNIV,SCH MED,DEPT PATHOL 2,GUNMA,JAPAN. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. NR 18 TC 17 Z9 17 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 1994 VL 25 IS 3 BP 271 EP 275 DI 10.1016/0046-8177(94)90199-6 PG 5 WC Pathology SC Pathology GA NF072 UT WOS:A1994NF07200010 PM 8150457 ER PT J AU ORD, DC EDELHOFF, S DUSHKIN, H ZHOU, LJ BEIER, DR DISTECHE, C TEDDER, TF AF ORD, DC EDELHOFF, S DUSHKIN, H ZHOU, LJ BEIER, DR DISTECHE, C TEDDER, TF TI CD19 MAPS TO A REGION OF CONSERVATION BETWEEN HUMAN CHROMOSOME-16 AND MOUSE CHROMOSOME-7 SO IMMUNOGENETICS LA English DT Article ID RECOMBINANT INBRED STRAINS; KINASE-DEPENDENT PATHWAY; B-CELL DIFFERENTIATION; LYMPHOCYTES-B; MONOCLONAL-ANTIBODY; GENE-CLUSTER; ANTIGEN; EXPRESSION; LOCALIZATION; ACTIVATION AB CD19 is a B lymphocyte cell surface protein expressed from the earliest stages of B lymphocyte development until their terminal differentiation into plasma cells. In this report the human CD19 gene (hCD19) was localized to band p11.2 on the proximal short arm of chromosome 16 by in situ hybridization to metaphase chromosomes, using hCD19 cDNA as probe. hCD19 gene localization was confirmed by polymerase chain reaction based analysis with hCD19-specific primers, using a panel of human/hamster somatic cell hybrid DNA as templates. The mouse CD19 gene (mCd19) was mapped to bands F3-F4 of chromosome 7 by in situ hybridization to metaphase chromosomes, using a mCD19 cDNA probe. Segregation analysis of nucleotide sequence polymorphisms in interspecific backcross progeny revealed linkage of mCd19 with hemoglobin beta (Hbb), Int-2, and H19, other loci previously mapped to the same region of mouse chromosome 7, confirming the localization of mCd19 to this region. The order of these loci was determined to be centromere - Hbb - mCd19 - H19 - Int-2 - telomere. The genetic distances between the loci examined, calculated from the recombination frequencies, suggested that mCd19 was located centrally between Hbb and H19. This region of mouse chromosome 7 is homologous to the region of human chromosome 16 to which the hCD19 gene maps. Multiple genes with a lymphocyte-related function also map to this conserved region including genes encoding the IL-4 receptor, CD11a, CD11b, CD11c, CD43 (leukosialin), and protein kinase C beta polypeptide. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV WASHINGTON,DEPT PATHOL SM30,SEATTLE,WA 98195. BRIGHAM & WOMENS HOSP,DIV GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA-54464, CA-34183]; NIAID NIH HHS [AI-26872] NR 29 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD MAR PY 1994 VL 39 IS 5 BP 322 EP 328 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA ND510 UT WOS:A1994ND51000003 PM 7513297 ER PT J AU GONG, JL MCCARTHY, KM ROGERS, RA SCHNEEBERGER, EE AF GONG, JL MCCARTHY, KM ROGERS, RA SCHNEEBERGER, EE TI INTERSTITIAL LUNG MACROPHAGES INTERACT WITH DENDRITIC CELLS TO PRESENT ANTIGENIC PEPTIDES DERIVED FROM PARTICULATE ANTIGENS TO T-CELLS SO IMMUNOLOGY LA English DT Article ID EPIDERMAL LANGERHANS CELLS; ALVEOLAR MACROPHAGES; ACCESSORY CELLS; LYMPH-NODES; HUMAN BLOOD; GM-CSF; RAT; IDENTIFICATION; EPITHELIUM; RESPONSES AB When the protective structural and functional barriers of the lung are breached, immune responses must be generated in order to contain invading micro-organisms. This requires the presence of accessory cells capable of phagocytosing and presenting immunogenic peptides to either naive or sensitized T cells. In contrast to dendritic cells (DC) present in the airway epithelium, those within the lung parenchyma do not readily engulf particulates and, therefore, other mechanisms must account for their apparent ability to present immunogenic peptides derived from micro-organisms. The purpose of the present study was to determine the extent to which interstitial macrophages (IM) interact with lung DC to process and present antigenic peptides, derived from particulate, heat-killed Listeria monocytogenes (HKL), to HKL-immune T cells. Results show that highly purified Ia(-) lung IM avidly phagocytose fluorescent-labelled HKL, but they do not present antigen to primed T cells. Their ability to present antigen is only modestly increased following interferon-gamma (IFN-gamma) stimulation. Conversely, mature DC isolated from the lung interstitium do not phagocytose fluorescent-labelled HKL. In antigen presentation assays, however, addition of 10% (25 x 10(3)/ml) Ia(-) IM to DC and HKL results in a two- to threefold increase in antigen presentation by DC to HKL-immune T cells. Conditioned medium (CM), generated by 2.5 x 10(4)/ml IM induced to phagocytose HKL, when administered to DC and HKL-sensitized T cells without added intact HKL, resulted in brisk mitogenesis, a response that did not occur in T cells sensitized to an irrelevant antigen. Conditioned medium derived from larger numbers of IM was inhibitory. When IM phagocytosed inert polystyrene beads, the resulting CM induced modest T-cell mitogenesis, suggesting that small amounts of cytokines were released. The results indicate that in small numbers, IM augment DC function, in part, by the release of antigenic peptides which are then presented by DC to T cells. When present in numbers greater than 50% of DC, however, they inhibit DC function, probably due to the release of soluble inhibitors. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM SCI & PHYSIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL36781] NR 40 TC 45 Z9 45 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 1994 VL 81 IS 3 BP 343 EP 351 PG 9 WC Immunology SC Immunology GA MZ259 UT WOS:A1994MZ25900003 PM 8206508 ER PT J AU DASGUPTA, JD GRANJA, CB YUNIS, EJ RELIAS, V AF DASGUPTA, JD GRANJA, CB YUNIS, EJ RELIAS, V TI MHC CLASS-I ANTIGENS REGULATE CD3-INDUCED TYROSINE PHOSPHORYLATION OF PROTEINS IN T-CELLS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD3; CLASS-I; MHC; TYROSINE PHOSPHORYLATION ID COMPLEX CLASS-I; MEDIATED SIGNAL TRANSDUCTION; HISTOCOMPATIBILITY ANTIGENS; LYMPHOCYTES-T; SURFACE MOLECULES; RECEPTOR COMPLEX; CROSS-LINKING; INSULIN-RECEPTOR; KINASE ACTIVITY; CD2 PATHWAY AB The MHC class I antigens enhance the T cell response to various mitogenic stimuli. Class I antigens co-cap and associate with the CD3 structure on these cells. The present work shows that co-aggregation of these MHC antigens with CD3 induces a sustained elevated Ca2+ response in T cells. The duration required for a 50% decline in peak response is five to 10 times longer when class I antigens are cross-linked with CD3 as compared to that when cells are stimulated through CD3 alone. Further analysis reveals that class I antigens prolong the duration of CD3-induced tyrosine phosphorylation of several proteins. No protein tyrosine kinase activity is found associated with these MHC antigens which could explain their influence on CD3 activation. Similarly, class I antigens do not depend on the membrane-bound protein tyrosine phosphatase CD45, since they elevate the degree of CD3-induced Ca2+ response in a CD45-deficient Jurkat cell line. On the contrary, in a CD45- HPB cell line defective in CD3 signaling, co-aggregation of class I antigens with CD3 does not induce Ca2+ flux. Therefore, the effect of class I antigens on CD3 function depends on the ability of CD3 to transduce a signal. Furthermore, cytofluorometric studies show that cross-linking of class I antigens with CD3 inhibits the internalization of the latter. Thus, class I antigens seem to prolong the duration of signal transduction through CD3 by retarding its down-regulation. RP DASGUPTA, JD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,BOSTON,MA 02115, USA. NR 61 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 1994 VL 6 IS 3 BP 481 EP 489 PG 9 WC Immunology SC Immunology GA NC479 UT WOS:A1994NC47900017 PM 8186200 ER PT J AU VIJAYKUMAR, M NARULA, J REDDY, KS KAPLAN, EL AF VIJAYKUMAR, M NARULA, J REDDY, KS KAPLAN, EL TI INCIDENCE OF RHEUMATIC-FEVER AND PREVALENCE OF RHEUMATIC HEART-DISEASE IN INDIA SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Review DE RHEUMATIC FEVER; VALVULAR DISEASE; RHEUMATIC HEART DISEASE AB Rheumatic heart disease (RHD) has been documented in Indian medical literature since the early nineteenth century, contrary to the popular belief that rheumatic fever (RF) and its sequelae were exclusively prevalent in temperate climates until the early twentieth century. Rheumatic heart disease has, in the past 50 years, emerged as a major contributor to cardiovascular morbidity in India. Despite the paucity of clear information regarding secular trends, the few available community surveys indicate that there are at present more than 1 million patients with RHD. Even a conservative estimate of the incidence of RP suggests that at least 50 000 new episodes occur every year. The younger age of onset (juvenile RHD) seen in India is a special feature of both public health and clinical importance. These patterns of RF and RHD, which may be similar to those in other developing countries, underscore the importance of effective public health strategies for prevention and control. C1 ALL INDIA INST MED SCI,CTR CARDIOTHORAC,DEPT CARDIOL,ANSARI NAGAR,NEW DELHI 110029,INDIA. APOLLO HOSP,MADRAS,INDIA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MINNESOTA,SCH MED,MINNEAPOLIS,MN 55455. NR 70 TC 28 Z9 28 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD MAR 1 PY 1994 VL 43 IS 3 BP 221 EP 228 DI 10.1016/0167-5273(94)90199-6 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ND505 UT WOS:A1994ND50500001 PM 8181878 ER PT J AU CLERMONT, AC BRITTIS, M SHIBA, T MCGOVERN, T KING, GL BURSELL, SE AF CLERMONT, AC BRITTIS, M SHIBA, T MCGOVERN, T KING, GL BURSELL, SE TI NORMALIZATION OF RETINAL BLOOD-FLOW IN DIABETIC RATS WITH PRIMARY INTERVENTION USING INSULIN PUMPS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RETINA; HEMODYNAMICS; DIABETES; INSULIN; RATS ID PROTEIN-KINASE-C; GLYCEMIC CONTROL; AUTO-REGULATION; CIRCULATION; GLUCOSE; HYPERGLYCEMIA; RETINOPATHY; HISTAMINE; DECREASE; SYSTEM AB Purpose. Prior results have demonstrated a significant reduction in retinal blood flow in streptozotocin (STZ)-induced diabetic rats. These studies were extended to investigate whether retinal blood flow changes, in the diabetic rat model, could be prevented with strict glycemic control using insulin pumps. Retinal blood flow changes also were measured during hyperoxia and after intravitreal histamine infusion to validate the methodology. Methods. Retinal blood flow changes were measured using video-based fluorescein angiography and computer-assisted image analysis. A total of 48 male Sprague-Dawley and 9 Brown Norway rats were used in these experiments. Retinal blood flow after primary insulin intervention was evaluated in diabetic rats implanted with miniosmotic insulin pumps within 24 hours of STZ-induced diabetes. Diabetic rats, not treated with insulin, were used for comparison. Results. Hyperoxia caused a significant (P = 0.001) reduction (54%) in retinal blood flow, whereas intravitreal infusion of 10(-3) M histamine caused a significant (P = 0.009) increase (108%) in retinal blood flow. Retinal blood flow in the primary insulin intervention group, after 1 week of diabetes, was not statistically different from retinal blood flow of nondiabetic controls as measured at baseline from the animals used in the hyperoxia and histamine infusion experiments. In contrast there was a significant (P = 0.0001) retinal blood flow reduction in the untreated diabetic group. Conclusions. The results showed that the local effect of histamine and hyperoxia on the retina produced the expected responses in retinal blood flow, further confirming the validity of the methodology. Primary insulin intervention demonstrated that strict glycemic control initiated immediately after induction of diabetes was sufficient to maintain normal retinal blood flow in STZ-induced diabetic rats. C1 BEETHAM EYE INST,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. FU NEI NIH HHS [EY05110] NR 45 TC 58 Z9 58 U1 0 U2 1 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 MAR PY 1994 VL 35 IS 3 BP 981 EP 990 PG 10 WC Ophthalmology SC Ophthalmology GA MZ261 UT WOS:A1994MZ26100027 PM 8125761 ER PT J AU HAHN, LB BERSON, EL DRYJA, TP AF HAHN, LB BERSON, EL DRYJA, TP TI EVALUATION OF THE GENE ENCODING THE GAMMA-SUBUNIT OF ROD PHOSPHODIESTERASE IN RETINITIS-PIGMENTOSA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RETINITIS PIGMENTOSA; RETINAL DEGENERATION; PHOSPHODIESTERASE; ROD PHOTORECEPTOR; RETINA ID HUMAN RETINAL DEGENERATION; RHODOPSIN GENE; GEL-ELECTROPHORESIS; CONE DYSTROPHY; ONE FORM; MUTATIONS; DNA; ERG AB Purpose. To determine whether defects in the gene encoding the gamma subunit of rod cyclic guanosine monophosphate-phosphodiesterase (PDE-g) cause some form of hereditary retinal degeneration or dysfunction. Methods. A restriction map, an intron/exon map, and a partial sequence of the human genomic locus corresponding to this gene were ascertained. Based on this information, the single-strand conformation polymorphism technique (SSCP) was used to screen the coding region as well as most splice donor and acceptor sites for mutations in a total of 704 unrelated patients with retinitis pigmentosa, Usher's syndrome type I or type II, Leber's congenital amaurosis, the Laurence-Moon-Bardet-Biedl syndrome, or other hereditary retinal disease. Results. Two frequent polymorphisms were found, as well as three rare sequence variations, none of which correlated with any phenotype examined. Conclusions. In view of these negative results and those of a previously published negative Southern blot analysis of an overlapping set of patients, it is unlikely that mutations in the PDE-g gene are a common cause of any of the forms of retinal degeneration or dysfunction so far examined. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BERMAN GUND LAB,BOSTON,MA. FU NEI NIH HHS [EY05321, EY08683, EY00169] NR 30 TC 19 Z9 20 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 MAR PY 1994 VL 35 IS 3 BP 1077 EP 1082 PG 6 WC Ophthalmology SC Ophthalmology GA MZ261 UT WOS:A1994MZ26100039 PM 8125719 ER PT J AU WALLACE, JE MOJAVERIAN, P LIN, CC KIM, HK HARRIS, SC CHEN, TJH RINALDI, MG AF WALLACE, JE MOJAVERIAN, P LIN, CC KIM, HK HARRIS, SC CHEN, TJH RINALDI, MG TI DETERMINATION OF SCH-39304 BY MEGABORE CAPILLARY GAS-LIQUID-CHROMATOGRAPHY SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article C1 SCHERING PLOUGH CORP,RES,DEPT DRUG METAB,KENILWORTH,NJ. VET ADM MED CTR,CHICAGO,IL 60612. PRECIS ANALYT LABS INC,SAN ANTONIO,TX 78216. AUDIE L MURPHY MEM VET ADM MED CTR,LAB SERV,SAN ANTONIO,TX 78284. RP WALLACE, JE (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD MAR-APR PY 1994 VL 18 IS 2 BP 118 EP 121 PG 4 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA NB984 UT WOS:A1994NB98400011 PM 8207932 ER PT J AU BRYAN, CL PATEFIELD, AJ COHEN, D NIELSEN, JL EMANUEL, B CALHOON, JH AF BRYAN, CL PATEFIELD, AJ COHEN, D NIELSEN, JL EMANUEL, B CALHOON, JH TI ASSESSMENT OF INJURY IN TRANSPLANTED AND NONTRANSPLANTED LUNGS AFTER 6 H OF COLD-STORAGE WITH GLUTATHIONE SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE LUNG INJURY; TRANSPLANTATION; NEUTROPHIL; FREE RADICAL; CANINE; PULMONARY EDEMA; LIPID PEROXIDATION ID PULMONARY REIMPLANTATION RESPONSE; ARTERY OCCLUSION; REPERFUSION; EDEMA; PERMEABILITY; DISULFIDE; TRANSPORT; PRESSURE; RAT AB Single-lung transplantation after 3 h of hypothermic storage produces bilateral lung injury [pulmonary reimplantation response (PRR)]. We hypothesized that glutathione (GSH) hypothermic storage would protect both lungs from PRR for extended preservation times and that differences in injury and protection would be realized between the graft and the nontransplanted lung. Mongrel dogs underwent left single-lung autotransplantation after preservation for 5-6 h in Euro-Collins (EC) solution, EC plus exogenous GSH (EC + GSH), or Viaspan (VIA) at 4 degrees C. Lung injury was measured in both lungs after 1 h of reperfusion. EC dogs demonstrated significant increases in lung edema, lipid peroxidation, and alveolar neutrophil recruitment in the lung graft and to a less extent in the nontransplanted right lung compared with control dogs (P < 0.05). Edema, lipid peroxidation, and alveolar neutrophils were significantly reduced in both lungs from EC + GSH and VIA dogs compared with lungs from EC dogs (P < 0.05). An increase in large-pore permeability was measured in the lung graft from EC dogs compared with all other lungs. Bronchoalveolar lavage fluid lactate dehydrogenase and total protein concentrations were elevated in both lungs from all three groups of transplanted dogs compared with those of control dogs (P < 0.05). These data suggest that GSH-containing solutions attenuate the PRR after 6 h of ischemic hypothermic storage but that the protection is incomplete. Mechanisms of injury affecting the lung graft during the PRR appear to differ from those affecting the nontransplanted lung. C1 UNIV TEXAS,AUDIE L MURPHY MEM VET HOSP,HLTH SCI CTR,DEPT SURG,DIV CARDIOTHORAC SURG,SAN ANTONIO,TX 78284. USAF,MED CTR,DEPT MED,SAN ANTONIO,TX 78284. USAF,MED CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. RP BRYAN, CL (reprint author), UNIV TEXAS,AUDIE L MURPHY VET HOSP,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE MED,SAN ANTONIO,TX 78284, USA. NR 33 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 1994 VL 76 IS 3 BP 1232 EP 1241 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA NB204 UT WOS:A1994NB20400037 PM 8005867 ER PT J AU PEACOCK, MD SCHENK, DA LAWRENCE, RA MORGAN, JA JENKINSON, SG AF PEACOCK, MD SCHENK, DA LAWRENCE, RA MORGAN, JA JENKINSON, SG TI ELIMINATION OF GLUTATHIONE-INDUCED PROTECTION FROM HYPERBARIC HYPEROXIA BY ACIVICIN SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE GAMMA-GLUTAMYL TRANSPEPTIDASE; HYPERBARIC OXYGEN TOXICITY; RAT ID GLUTAMYL-TRANSFERASE TRANSPEPTIDASE; ISOLATED RAT HEPATOCYTES; OXYGEN-TOXICITY; SELENIUM DEFICIENCY; OXIDATIVE INJURY; EXOGENOUS GLUTATHIONE; PLASMA GLUTATHIONE; LUNG GLUTATHIONE; SMALL-INTESTINE; LYMPHOID-CELLS AB Glutathione (GSH) administered intraperitoneally significantly prolongs the time to initial seizure and survival time of rats exposed to hyperbaric hyperoxia (HBO). Acivicin is an antitumor antibiotic that is an inhibitor of gamma-glutamyl transpeptidase (GGT), an enzyme necessary for the breakdown and transport across cell membranes of GSH. To determine whether acivicin treatment alters GSH-induced protection from HBO, rats were dosed with 25 mg/kg of acivicin or vehicle 1 h before O-2 exposure at an inspired O-2 fraction at 1.0 at 4 ATA. Immediately before exposure, rats received GSH (1 mmol/kg) or vehicle. Time to seizure and time to death were recorded during exposure by direct observation. In separate groups of rats on the same dosing schedule, plasma GSH, renal GGT, and brain GGT were measured 15 min after the GSH injection without HBO exposure and 100 min after the beginning of HBO exposure. Renal GGT was decreased to 2.5% of control and brain GGT to 37% of control in the acivicin-dosed rats. Plasma GSH increased 3-fold in rats given acivicin alone, 52-fold in rats given GSH alone, and 84-fold in rats receiving both acivicin and GSH. Rats dosed with GSH alone had significantly prolonged times to seizure and death compared with all other groups. Rats dosed with GSH after receiving acivicin were not protected from HBO despite the large increase in plasma GSH that occurred in these animals. GSH treatment did not increase tissue GSH in lung, liver, or brain at 160 or 200 min of exposure. These data support the hypothesis that acivicin treatment abolishes GSH-induced protection from HBO and that elevations in plasma GSH do not protect acivicin-treated animals. C1 UNIV TEXAS,HLTH SCI CTR,BROOKE ARMY MED CTR,WILFORD HALL USAF MED CTR,LUNG METAB UNIT,SAN ANTONIO,TX. AUDIE L MURPHY VET AFFAIRS HOSP,SAN ANTONIO,TX 78284. NR 44 TC 12 Z9 12 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 MAR PY 1994 VL 76 IS 3 BP 1279 EP 1284 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA NB204 UT WOS:A1994NB20400044 PM 7911799 ER PT J AU CHEN, AP HILLMAN, JD DUNCAN, M AF CHEN, AP HILLMAN, JD DUNCAN, M TI L-(+)-LACTATE DEHYDROGENASE-DEFICIENCY IS LETHAL IN STREPTOCOCCUS-MUTANS SO JOURNAL OF BACTERIOLOGY LA English DT Note ID BACTERIOCIN; EXPRESSION; CHROMOSOME; CLONING AB The previously cloned gene for L-(+)-lactate dehydrogenase (LDH) from Streptococcus mutans was mutagenized in vitro. An Escherichia coli transformant which expressed a thermolabile LDH activity was identified. The Idh(Ts) gene was introduced into S. mutans on a suicide vector to create a heterodiploid expressing both wild-type and thermolabile LDH activities. Self-recombinants which had only one Idh gene were isolated. One of these clones expressed only the thermolabile LDH activity. This isolate grew well at 30 degrees C but did not grow at 42 degrees C under a variety of cultivation conditions, thereby proving that LDH deficiency is lethal in S. mutans in the absence of compensatory mutations. C1 UNIV FLORIDA,COLL DENT,DEPT ORAL BIOL,GAINESVILLE,FL 32610. FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02115. FU NIDCR NIH HHS [DEO4529] NR 14 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 1994 VL 176 IS 5 BP 1542 EP 1545 PG 4 WC Microbiology SC Microbiology GA MY351 UT WOS:A1994MY35100048 PM 8113201 ER PT J AU WATTENMAKER, I CONCEPCION, M HIBBERD, P LIPSON, S AF WATTENMAKER, I CONCEPCION, M HIBBERD, P LIPSON, S TI UPPER-AIRWAY OBSTRUCTION AND PERIOPERATIVE MANAGEMENT OF THE AIRWAY IN PATIENTS MANAGED WITH POSTERIOR OPERATIONS ON THE CERVICAL-SPINE FOR RHEUMATOID-ARTHRITIS SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ENDOTRACHEAL INTUBATION; CAROTID ENDARTERECTOMY; FIBEROPTIC BRONCHOSCOPE AB We reviewed the records of 128 patients who had a total of 128 consecutive posterior operations on the cervical spine for problems related to rheumatoid arthritis. Our purpose was to examine perioperative complications related to the airway. The patients were divided into two groups for analysis on the basis of the technique of intubation that had been used. An upper-airway obstruction developed after extubation in eight (14 per cent) of the fifty-eight patients who had been intubated without fiberoptic assistance compared with one (1 per cent) of the seventy patients who had been intubated fiberoptically (p = 0.02). The two groups had similar characteristics with regard to age, sex, severity of the myelopathy, American Rheumatology Association classification, American Society of Anesthesiologists physical status classification, cigarette use, duration of the arthritis, use of preoperative traction, use of steroids (both preoperatively and intraoperatively), size of the endotracheal tube, duration of the operation, total duration of the anesthesia, intraoperative fluid balance, and type of immediate immobilization of the neck. The only significant difference between the groups was the time to extubation, which averaged 17.9 hours in the fiberoptic group and 10.6 hours in the non-fiberoptic group (p = 0.02). Logistic regression analysis showed that non-fiberoptic intubation was the significant risk factor, even when allowance was made for the difference in the lengths of time to extubation. We concluded that this life-threatening complication can be minimized with fiberoptic management of the airway. C1 BRIGHAM & WOMENS HOSP,DEPT ANESTHESIOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT INFECT DIS & EPIDEMIOL,BOSTON,MA 02114. NR 22 TC 36 Z9 39 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 MAR PY 1994 VL 76A IS 3 BP 360 EP 365 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA ND139 UT WOS:A1994ND13900006 PM 8126041 ER PT J AU DEALMEIDA, JB HOLTZMAN, EJ PETERS, P ERCOLANI, L AUSIELLO, DA STOW, JL AF DEALMEIDA, JB HOLTZMAN, EJ PETERS, P ERCOLANI, L AUSIELLO, DA STOW, JL TI TARGETING OF CHIMERIC G-ALPHA(I) PROTEINS TO SPECIFIC MEMBRANE DOMAINS SO JOURNAL OF CELL SCIENCE LA English DT Article DE G-PROTEIN; TARGETING SIGNAL; PLASMA MEMBRANE; GOLGI; IMMUNOFLUORESCENCE ID BETA-GAMMA DIMERS; ALPHA-SUBUNITS; COS CELLS; GS-ALPHA; IDENTIFICATION; ACTIVATION; BINDING; MYRISTOYLATION; LOCALIZATION; ASSOCIATION AB Heterotrimeric guanine nucleotide-regulatory (G) proteins are associated with a variety of intracellular membranes and specific plasma membrane domains. In polarized epithelial LLC-PK1 cells we have shown previously that endogenous Galpha(i-2) is localized on the basolateral plasma membrane, whereas Galpha(i-3) is localized on Golgi membranes. The targeting of these highly homologous Galpha(i) proteins to distinct membrane domains was studied by the transfection and expression of chimeric Galpha(i) proteins in LLC-PK1 cells. Chimeric cDNAs were constructed from the cDNAs for Galpha(i-3) and Galpha(i-2) and introduced into a pMXX eukaryotic expression vector containing a mouse metaltothionein-I promotor. Stably transfected cell lines were produced that expressed either Galpha(i-2/3) or Galpha(i-3/2) chimeric proteins. Chimeric and endogenous Galpha(i) proteins were detected in cells using specific carboxy-terminal peptide antibodies. Immunofluorescence staining was used to localize endogenous and chimeric Galpha(i) proteins in LLC-PK1 cells. The staining of chimeric proteins was detected as an increased intensity of staining on membranes containing endogenous Galpha(i) proteins. Using confocal microscopy and image analysis we localized Galpha(i-2) to a specific sub-domain of the lateral membrane of polarized cells, the chimeric Galpha(i-3/2) protein was then shown to colocalize with endognenous Galpha(i-2) in the same lateral plasma membrane domain. The chimeric Galpha(i-2/3) protein colocalized with endogenous Galpha(i-3) on Golgi membranes in LLC-PK1 cells. These results show that chimeric Galpha(i) proteins were targeted to the same membrane domains as endogenous Galpha(i) proteins and the specificity of their membrane targeting was conferred by the carboxy-terminal end of the proteins. These data provide the first evidence for specific targeting information contained in the carboxy termini of Galpha(i) proteins, which appears to be independent of amino-terminal membrane attachment sites in these proteins. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK 19406-16, DK42543, P01 DK 38452-07] NR 27 TC 35 Z9 35 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR PY 1994 VL 107 BP 507 EP 515 PN 3 PG 9 WC Cell Biology SC Cell Biology GA ND705 UT WOS:A1994ND70500016 PM 8006069 ER PT J AU IADECOLA, C PELLIGRINO, DA MOSKOWITZ, MA LASSEN, NA AF IADECOLA, C PELLIGRINO, DA MOSKOWITZ, MA LASSEN, NA TI NITRIC-OXIDE SYNTHASE INHIBITION AND CEREBROVASCULAR REGULATION SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CEREBRAL BLOOD FLOW; CEREBRAL ISCHEMIA; FUNCTIONAL ACTIVATION; HYPERCAPNIA; HYPOXIA; VASODILATION ID CEREBRAL BLOOD-FLOW; CEREBELLAR FASTIGIAL NUCLEUS; MONOMETHYL-L-ARGININE; DOUBLE-EDGED ROLE; RELAXING FACTOR; BASILAR ARTERIES; PIAL ARTERIOLES; NEURONAL DEATH; RAT MODEL; ENDOTHELIUM AB There is increasing evidence that nitric oxide (NO) is an important molecular messenger involved in a wide variety of biological processes. Recent data suggest that NO is also involved in the regulation of the cerebral circulation. Thus, NO participants in the maintenance of resting cerebrovascular tone and may play an important role in selected vasodilator responses of the cerebral circulation. Furthermore, evidence has been presented suggesting that NO participates in the mechanisms of cerebral ischemic damage. Despite the widespread attention that NO has captured in recent years and the large number of studies that have been published on the subject, there is considerable controversy regarding the role of this agent in cerebrovascular regulation and in ischemic damage. In this paper the results of investigations on NO and the cerebral circulation are reviewed and the evidence for and against a role of NO is critically examined. C1 UNIV ILLINOIS,DEPT ANESTHESIOL,CHICAGO,IL. MASSACHUSETTS GEN HOSP,HARVARD MED SCH,STROKE RES LAB,BOSTON,MA 02114. BISPEBJERG HOSP,DEPT CLIN PHYSIOL,DK-2400 COPENHAGEN,DENMARK. RP IADECOLA, C (reprint author), UNIV MINNESOTA,DEPT NEUROL,CEREBROVASC BIOL & STROKE LAB,BOX 295 UMHC,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. RI Moskowitz, Michael/D-9916-2011 NR 154 TC 542 Z9 552 U1 2 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 MAR PY 1994 VL 14 IS 2 BP 175 EP 192 PG 18 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA MX608 UT WOS:A1994MX60800001 PM 7509338 ER PT J AU FREEDMAN, JE WIRSHING, WC RUSSELL, AT BRAY, MP UNUTZER, J AF FREEDMAN, JE WIRSHING, WC RUSSELL, AT BRAY, MP UNUTZER, J TI ABSENCE STATUS SEIZURES DURING SUCCESSFUL LONG-TERM CLOZAPINE TREATMENT OF AN ADOLESCENT WITH SCHIZOPHRENIA SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article AB This article reports the appearance of complex partial seizures during the course of successful use of the atypical neuroleptic clozapine in a 15 year old with neuroleptic-resistant schizophrenia. After 7 months of clozapine treatment, and 1 week after a gradual increase in dose to 550 mg, the adolescent began to develop periods of nausea and a ''spacey feeling'' that lasted for several minutes to hours at a time. A diagnosis of absence status was confirmed by electroencephalography (EEG). It was treated effectively by dose reduction (to 400 mg daily) without the use of anticonvulsant medications. A 3-year follow-up showed the generally sustained efficacy of this treatment, without recurrence of absence status seizures. This appears to be the first report of an absence seizure apparently associated with clozapine treatment. Published reports on 80 adolescents suggest an estimated prevalence of clozapine-induced seizures at about 4% (compared to 1-5% in adults, depending on dose), whereas 60% developed mild to marked EEG abnormalities. The current data on the safety and efficacy of clozapine for treating adolescents with schizophrenia remain preliminary. These data support the clinical recommendation that an EEG be obtained before adolescents are started on treatment with clozapine. RP FREEDMAN, JE (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT PSYCHIAT,11301 WILSHIRE BLVD,BLDG 20,LOS ANGELES,CA 90073, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD SPR PY 1994 VL 4 IS 1 BP 53 EP 62 DI 10.1089/cap.1994.4.53 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA NE990 UT WOS:A1994NE99000005 ER PT J AU ABE, K IWANAGA, H INADA, E AF ABE, K IWANAGA, H INADA, E TI EFFECT OF NICARDIPINE AND DILTIAZEM ON INTERNAL CAROTID-ARTERY BLOOD-FLOW VELOCITY AND LOCAL CEREBRAL BLOOD-FLOW DURING CEREBRAL ANEURYSM SURGERY FOR SUBARACHNOID HEMORRHAGE SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE ANESTHESIA, NEUROSURGICAL; ANEURYSM, CEREBRAL; CEREBRAL BLOOD FLOW; DILTIAZEM; DOPPLER ULTRASOUND; NICARDIPINE AB Study Objective: To determine the hemodynamic effects of a bolus injection of nicardipine 1 mg or diltiazem 5 mg on local cerebral blood flow (LCBF) and internal carotid blood flow velocity (ICBFV) with isoflurane anesthesia. Design: Randomized study. Setting: Inpatient neurosurgery and anesthesia clinic at a city hospital. Patients: 26 patients with subarachnoid hemorrhage who were scheduled for cerebral aneurysm clipping. Interventions: A bolus injection of either nicardipine or diltiazem was administered to patients whose systolic blood pressure increased to over 150 mmHg after opening of the dura. Measurements and Main Results: After the bolus injection, both drugs rapidly decreased arterial blood pressure. Nicardipine increased LCBF [before injection, 42.1 +/- 12.3 ml/100 g/min; after injection, 47 +/- 10.7 ml/100g/min; (p < 0.05 vs. control); after recovery 42.4 +/- 11.1 cm/sec], but diltiazem did not change LCBF: Nicardipine 1 mg moderately increased ICBFV [before injection, 34.2 +/- 9.3 cm/sec; after injection, 40.6 +/- 8.7 cm/sec (p < 0.01 vs, control); after recovery, 34.1 +/- 8.9 cm/sec], but diltiazem did not change ICBFV In addition, venous partial oxygen pressure and saturation of the internal jugular did not change throughout the study. There was a close correlation between presurgical neurologic status and LCBF (rs = - 0.743; p < 0. 01) and ICBFV (rs = - 0. 721; p < 0.01). Conclusions: Nicardipine increased LCBF and ICBFV: but diltiazem did not change either These results suggest that both drugs are useful and safe for the treatment of intraoperative hypertension during cerebral aneurysm surgery. RP ABE, K (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 26 Z9 30 U1 0 U2 6 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 MAR-APR PY 1994 VL 6 IS 2 BP 99 EP 105 DI 10.1016/0952-8180(94)90004-3 PG 7 WC Anesthesiology SC Anesthesiology GA NG205 UT WOS:A1994NG20500003 PM 8204245 ER PT J AU SHEPHERD, KE FAULKNER, CS LEITER, JC AF SHEPHERD, KE FAULKNER, CS LEITER, JC TI ACUTE EFFECTS OF SUCRALFATE ASPIRATION - CLINICAL AND LABORATORY OBSERVATIONS SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE ASPIRATION PNEUMONITIS; ASPIRATION SYNDROMES; GASTRIC STRESS BLEEDING; NOSOCOMIAL PNEUMONIA; SUCRALFATE AB Study Objective: To assess the complications associated with the aspiration of sucralfate. Design: Clinical (case report) and bench observations. Setting: lnpatient intensive care unit and experimental animal laboratory. Subjects: The case of a critically ill patient who aspirated sucralfate is presented. Fifteen Sprague-Dawley rats served as experimental animals to investigate the acute histologic effects of large-volume aspiration of sucralfate. Interventions: The patient underwent emergent intubation to relieve acute upper airway obstruction. All the animals were anesthetized and had tracheostomies performed. The experimental groups had acidic intratracheal injections of 2 ml/kg of a nonparticulate liquid (pH, 2.3; n = 6) or a sucralfate aspirate (1 ml/kg of a 5% sucralfate suspension of pH 3.6, followed by 1 ml/kg 0.1 of normal hydrochloric acid of pH 1.0; n = 4). Four hours after simulated aspiration, the rats were sacrificed and their lungs removed for histologic examination by light microscopy. Measurements and Main Results: Differences were noted in histopathologic injury in the experimental groups compared to the control group using a numeric scoring scale. Nonparticulate acidic liquid aspiration caused a significant increase (p < 0.05) in inflammation. Sucralfate caused a significant increase (p < 0.05) in lung hemorrhage. A nonsignificant trend was seen with simulated sucralfate aspiration for edema and inflammation. No long-term sequelae were attributed to the clinical aspiration episode. Conclusions: Acute complications associated with aspiration of sucralfate have been identified. In the laboratory setting, simulated aspiration of sucralfate led to acute lung injury. RP SHEPHERD, KE (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL01998] NR 0 TC 3 Z9 3 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 MAR-APR PY 1994 VL 6 IS 2 BP 119 EP 123 DI 10.1016/0952-8180(94)90008-6 PG 5 WC Anesthesiology SC Anesthesiology GA NG205 UT WOS:A1994NG20500007 PM 8204229 ER PT J AU LEE, MM GUSTAFSON, ML UKIYAMA, E DONAHOE, PK MACLAUGHLIN, DT WEXLER, M KEEPING, HS AF LEE, MM GUSTAFSON, ML UKIYAMA, E DONAHOE, PK MACLAUGHLIN, DT WEXLER, M KEEPING, HS TI DEVELOPMENTAL-CHANGES IN MULLERIAN-INHIBITING SUBSTANCE IN THE CYNOMOLGUS MONKEY, MACACA-FASCICULARIS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; SEX-DETERMINING REGION; DUCT REGRESSION; SERTOLI CELLS; HORMONE; GENE; TESTOSTERONE; EXPRESSION; RADIOIMMUNOASSAY; DIFFERENTIATION AB Mullerian inhibiting substance (MIS) is a glycoprotein hormone produced in Sertoli cells of the fetal and postnatal testis, and granulosa cells of the pubertal ovary. We examined MIS expression in a nonhuman primate, the cynomolgus macaque monkey (Macaca fascicularis), to define an animal model for studying MIS gene regulation. Changes in testicular MIS mRNA with age were assessed by in situ hybridization of prepubertal to adult testes, Northern analysis of pubertal and adult specimens, and determination of serum MIS concentrations from infancy to adulthood. We found that MIS expression was highest in the youngest animals and decreased progressively with increasing age. Serum MIS concentrations correlated inversely with increasing age (r = -0.74), body weight (r = -0.79), and testicular volume (r = -0.73), but not with testosterone levels (r = -0.35). The mean MIS concentrations +/- SEM for the four developmental age groups were 270.6 +/- 23.8 (infants), 195.5 +/- 18.5 (juveniles), 102.7 +/- 28.4 (peripubertals), and 51.6 +/- 7.1 (adults). This study confirms that nonhuman primate and human MIS are highly homologous and have similar developmental patterns. The normative data for serum MIS concentrations in cynomolgus monkeys at different ages and developmental stages will be invaluable for further work examining MIS regulation. C1 MASSACHUSETTS GEN HOSP, PEDIAT SURG RES LAB, BOSTON, MA 02114 USA. RHODE ISL HOSP, DEPT UROL, PROVIDENCE, RI 02902 USA. RP LEE, MM (reprint author), MASSACHUSETTS GEN HOSP, PEDIAT ENDOCRINE UNIT, ACC 709, BOSTON, MA 02114 USA. OI Lee, Mary/0000-0002-7204-4884 FU NCI NIH HHS [CA-17393]; NICHD NIH HHS [HD-25272]; NIDDK NIH HHS [DK-02129] NR 43 TC 10 Z9 10 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 MAR PY 1994 VL 78 IS 3 BP 615 EP 621 DI 10.1210/jc.78.3.615 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ307 UT WOS:A1994MZ30700019 PM 8126132 ER PT J AU FINKELSTEIN, JS CLEARY, RL BUTLER, JP ANTONELLI, R MITLAK, BH DERASKA, DJ ZAMORAQUEZADA, JC NEER, RM AF FINKELSTEIN, JS CLEARY, RL BUTLER, JP ANTONELLI, R MITLAK, BH DERASKA, DJ ZAMORAQUEZADA, JC NEER, RM TI A COMPARISON OF LATERAL VERSUS ANTERIOR-POSTERIOR SPINE DUAL-ENERGY X-RAY ABSORPTIOMETRY FOR THE DIAGNOSIS OF OSTEOPENIA SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE DENSITOMETRY; PHOTON-ABSORPTIOMETRY; POSTMENOPAUSAL WOMEN; LUMBAR SPINE; VERTEBRAL FRACTURES; MINERAL DENSITY; OSTEOPOROSIS; RADIOGRAPHY; MASS; CALCIFICATION AB Because bone mineral density (BMD) measurements at various sites differ in the relative amounts of cortical and trabecular bone that they assess, they also differ in their sensitivity for detecting osteopenia. Lateral spine dual energy x-ray absorptiometry (DXA) allows measurement of BMD of the vertebral bodies, which contain mainly trabecular bone, without contribution from the posterior vertebral elements, which are rich in cortical bone. Thus, we hypothesized that lateral spine DXA would detect osteopenia more frequently than anterior-posterior (AP) spine DXA. To assess the ability of DXA to estimate trabecular bone mass, we compared AP and lateral DXA spine measurements with trabecular bone measurements by quantitative computed tomography (QCT) in 58 patients. We then compared AP vs. lateral spine DXA measurements in 1) 300 women referred for routine bone densitometry, 2) 30 glucocorticoid-treated women, and 3) 44 women with vertebral compression fractures. To compare short term reproducibility, we performed repeat AP and lateral DXA scans in 50 women. RP FINKELSTEIN, JS (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, ENDOCRINE UNIT, BULFINCH 3, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066] NR 30 TC 92 Z9 93 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 1994 VL 78 IS 3 BP 724 EP 730 DI 10.1210/jc.78.3.724 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MZ307 UT WOS:A1994MZ30700037 PM 8126149 ER PT J AU KATSANIS, GP SPARGO, J FERRARO, MJ SUTTON, L JACOBY, GA AF KATSANIS, GP SPARGO, J FERRARO, MJ SUTTON, L JACOBY, GA TI DETECTION OF KLEBSIELLA-PNEUMONIAE AND ESCHERICHIA-COLI STRAINS PRODUCING EXTENDED-SPECTRUM BETA-LACTAMASES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TRANSFERABLE ENZYMATIC RESISTANCE; CONFERRING RESISTANCE; CEFTAZIDIME; CEPHALOSPORINS; AZTREONAM; ENTEROBACTERIACEAE; COMBINATION; ANTIBIOTICS; SULBACTAM; OUTBREAK AB Plasmids encoding extended-spectrum beta-lactamases of the TEM, SHV, and AmpC families were introduced into common Escherichia coli and Klebsiella pneumoniae hosts to create a homogeneous panel for evaluating the abilities of five test systems to detect resistance to eight beta-lactam antibiotics. Although MICs, as determined by agar dilution or E test strips, were increased and disk diffusion zone diameters were diminished, breakpoints for resistance were often not reached, and neither approach was sensitive in detecting resistance to oxyimino-beta-lactams. The MicroScan 18-h microdilution or Vitek rapid automated procedures were similarly insensitive. Ceftazidime was the best single test antibiotic for detecting extended-spectrum beta-lactamase production. beta-Lactamases TEM-7 and TEM-12 were particularly difficult to detect. Because of such difficulties, the prevalence of extended-spectrum beta-lactamases is likely to be greater than is currently appreciated. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MICROBIOL LAB,BOSTON,MA 02114. FU NIAID NIH HHS [AI20415] NR 29 TC 106 Z9 111 U1 1 U2 1 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 MAR PY 1994 VL 32 IS 3 BP 691 EP 696 PG 6 WC Microbiology SC Microbiology GA MW516 UT WOS:A1994MW51600019 PM 8195380 ER PT J AU ACHENBACHNG, J SIAO, TCP MAVROUDAKIS, N CHIAPPA, KH KIERS, L AF ACHENBACHNG, J SIAO, TCP MAVROUDAKIS, N CHIAPPA, KH KIERS, L TI EFFECTS OF ROUTINE HYPERVENTILATION ON PCO2 AND PO2 IN NORMAL SUBJECTS - IMPLICATIONS FOR EEG INTERPRETATIONS SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; HYPERVENTILATION; BLOOD GASES ID MOYAMOYA DISEASE AB There are few data in the EEG literature describing the time course of hyperventilation-(HV) induced changes in blood gases, despite this being a routine activating procedure. We studied changes in blood gases and EEG in nine normal adult subjects before, during, and after HV. The mean PCO2 fell 18 mm Hg from the baseline during HV and recovered in 7 min. The mean PO2 rose 7 mm Hg during HV and fell to 25 mm Hg below baseline 5 min after HV. The PCO2 recovery period is longer than is usually assumed in clinical EEG. The PO2 fall to a nadir at 5 min after the end of HV suggests that close attention should be paid to this period, as is confirmed by the re-buildup seen in moyamoya disease. Despite uniform changes in blood gases, the EEG median power frequency change showed marked variability; on average, it dropped by 1 Hz during HV and returned to baseline within 2 min of resumption of normal respiration. The EEG root-mean-square power showed a 200% increase during HV and also had returned to normal within 2 min. RP ACHENBACHNG, J (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,EEG LAB,BIGELOW 12,BOSTON,MA 02114, USA. RI Mavroudakis, Nicolas/A-6801-2010 NR 24 TC 16 Z9 17 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD MAR PY 1994 VL 11 IS 2 BP 220 EP 225 DI 10.1097/00004691-199403000-00007 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NJ073 UT WOS:A1994NJ07300007 PM 8051307 ER PT J AU LOEHRER, PJ ELSON, P DREICER, R HAHN, R NICHOLS, CR WILLIAMS, R EINHORN, LH AF LOEHRER, PJ ELSON, P DREICER, R HAHN, R NICHOLS, CR WILLIAMS, R EINHORN, LH TI ESCALATED DOSAGES OF METHOTREXATE, VINBLASTINE, DOXORUBICIN, AND CISPLATIN PLUS RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR IN ADVANCED UROTHELIAL CARCINOMA - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP TRIAL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TRANSITIONAL-CELL-CARCINOMA; CHEMOTHERAPY; TUMORS C1 INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. DANA FARBER CANC CTR,DEPT BIOSTAT,BOSTON,MA. UNIV IOWA,IOWA CITY,IA. MAYO CLIN,ROCHESTER,MN. FU NCI NIH HHS [R10 CA 28171-04, 2 R 35 CA 39844-08]; NCRR NIH HHS [MO 1 RR 00750-06] NR 12 TC 89 Z9 89 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1994 VL 12 IS 3 BP 483 EP 488 PG 6 WC Oncology SC Oncology GA MZ763 UT WOS:A1994MZ76300007 PM 7509853 ER PT J AU BAER, L AF BAER, L TI FACTOR-ANALYSIS OF SYMPTOM SUBTYPES OF OBSESSIVE-COMPULSIVE DISORDER AND THEIR RELATION TO PERSONALITY AND TIC DISORDERS SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 146th Annual Meeting of the American-Psychiatric-Association CY MAY 22-27, 1993 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID TOURETTES DISORDER AB Despite advances in our understanding of the pathology and genetics of obsessive compulsive disorder (OCD) and in our ability to successfully treat patients with medications and behavioral psychotherapy, the identification of homogeneous subgroups of patients with OCD has remained elusive. Once identified, such subgroups may be found related to treatment response, biological markers, or genetic transmission of OCD. To clarify identification of symptom subtypes, my colleagues and I administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Symptom Checklist to 107 patients with OCD and applied principal components analysis (e.g., factor analysis) to these data. We then examined the correlations between these factor scores and the presence of comorbid tic and personality disorders, which are thought to be related to OCD. We found that three factors, which we named ''symmetry/hoarding,'' ''contamination/cleaning,'' and ''pure obsessions,'' best explained the symptoms of the Y-BOCS Symptom Checklist. Only the first factor was significantly related to comorbid obsessive compulsive personality disorder or to a lifetime history of Tourette's syndrome or chronic tic disorder. Implications of these findings regarding possible clinical utility are discussed. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BAER, L (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BIOSTAT & COMP UNIT,E BLDG 149,13TH ST,FLOOR 9,BOSTON,MA 02129, USA. NR 31 TC 344 Z9 353 U1 1 U2 16 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 1994 VL 55 SU S BP 18 EP 23 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA NG369 UT WOS:A1994NG36900004 PM 8077163 ER PT J AU LORR, M STRACK, S AF LORR, M STRACK, S TI PERSONALITY PROFILES OF POLICE CANDIDATES SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID OFFICERS; CLUSTERS AB Recently, Eber (1991) reported on several large-scale studies of law enforcement candidates. The main measures were the two parts of the Clinical Analysis Questionnaire (Krug, Cattell, & IPAT, 1980). Part I consists of the 16 Personality Factor Questionnaire Scales, while Part II is devoted to 12 measures of psychopathology. The most striking finding was a clear personality profile characterized by a strong pattern of self-discipline or Control, Tough Poise, and low Anxiety. Our study hypothesis was that several police personality profiles would be found. This conjecture was tested on the 16PF scores of two samples of 275 police candidates by means of the Ward (1963) hierarchical clustering procedure and the Milligan/Sokal (1980) nonhierarchical K-means cluster procedures. Three distinct score profiles were isolated in both samples. C1 US DEP VET AFFAIRS,OUTPATIENT CLIN,LOS ANGELES,CA. RP LORR, M (reprint author), CATHOLIC UNIV AMER,LIFE CYCLE INST,WASHINGTON,DC 20064, USA. NR 26 TC 6 Z9 6 U1 3 U2 6 PU CLINICAL PSYCHOLOGY PUBL CO PI BRANDON PA 4 CONANT SQUARE, BRANDON, VT 05733 SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAR PY 1994 VL 50 IS 2 BP 200 EP 207 DI 10.1002/1097-4679(199403)50:2<200::AID-JCLP2270500208>3.0.CO;2-1 PG 8 WC Psychology, Clinical SC Psychology GA NE675 UT WOS:A1994NE67500007 PM 8014241 ER PT J AU VANHOUTE, J AF VANHOUTE, J TI ROLE OF MICROORGANISMS IN CARIES ETIOLOGY SO JOURNAL OF DENTAL RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Use of Chemotherapeutic Agents for Caries Prevention, at the 70th General Session of the International-Association-for-Dental-Research CY JUL 01, 1992 CL GLASGOW, SCOTLAND SP INT ASSOC DENT RES DE DENTAL CARIES; CARBOHYDRATES; STREPTOCOCCUS; HYDROGEN ION CONCENTRATION; SALIVA ID ROOT-SURFACE CARIES; HUMAN DENTAL PLAQUE; SALIVARY FILM VELOCITY; STREPTOCOCCUS-MUTANS; ENAMEL DEMINERALIZATION; ARTIFICIAL PLAQUE; GNOTOBIOTIC-RATS; DIFFERENT SITES; HUMAN DENTITION; MATRIX MATERIAL AB The microbial etiology of dental caries is discussed in terms of the dynamic relationship among the dental plaque microbiota, dietary carbohydrate, saliva, and the pH-lowering and cariogenic potential of dental plaque. The evidence supports a concept of caries as a dietary carbohydrate-modified bacterial infectious disease. Its key feature is a dietary carbohydrate-induced enrichment of the plaque microbiota with organisms such as the mutans streptococci and lactobacilli which causes an increase of plaque's pH-lowering and cariogenic potential. The shift in the plaque proportions of these organisms appears to be related to their relatively high acid tolerance. A large body of evidence also supports a major effect of saliva on caries development. Integration of salivary effects with the concept of caries as a dietary carbohydrate-modified bacterial infectious disease suggests a broader concept which includes a major role of saliva in the regulation of the exposure of tooth surfaces to carbohydrate and of plaque acidity and, hence, the microbial composition and the pH-lowering and cariogenic potential of dental plaque. It is proposed that caries occurs preferentially in dentition sites characterized by a relatively high exposure to carbohydrate and diminished salivary effects. Some implications of this concept are discussed. RP VANHOUTE, J (reprint author), FORSYTH DENT CTR,DEPT ORAL MICROBIOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-07009, DE-07493] NR 85 TC 293 Z9 304 U1 5 U2 27 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 MAR PY 1994 VL 73 IS 3 BP 672 EP 681 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NG382 UT WOS:A1994NG38200013 PM 8163737 ER PT J AU LEE, RS GRUSBY, MJ GLIMCHER, LH WINN, HJ AUCHINCLOSS, H AF LEE, RS GRUSBY, MJ GLIMCHER, LH WINN, HJ AUCHINCLOSS, H TI INDIRECT RECOGNITION BY HELPER-CELLS CAN INDUCE DONOR-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN-VIVO SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SKIN ALLOGRAFT-REJECTION; ANTIGEN-PRESENTING CELLS; MONOCLONAL-ANTIBODIES; LINKED RECOGNITION; INVIVO; RESPONSES; DETERMINANTS; ALLOANTIGENS; GENERATION; GRAFTS AB In vitro studies have revealed that help for cytotoxic T lymphocyte (CTL) induction can be mediated through several pathways, including direct recognition of allogeneic class II antigens by CD4(+) cells, direct recognition of allogeneic class I antigens by ''CD4-independent'' CD8(+) cells, and ''indirect'' recognition of peptides of alloantigens presented in association with self class II molecules. Whereas good evidence for the two direct pathways is available in vivo, there is relatively little evidence to show that indirect recognition can initiate graft rejection. This study examined the role of indirect allorecognition during the generation of CTLs in mice as they rejected major histocompatibility complex (MHC) class II-deficient skin after depletion of CD8(+) T cells in vivo. Recipients were depleted of CD8(+) T cells by in vivo treatment with anti-CD8 monoclonal antibody and then grafted with allogeneic skin lacking MHC class II antigens. The mice rejected the skin grafts rapidly. Although flow cytometry showed marked depletion of CD8(+) T cells in these mice, we found that (a) CD8(+) CTLs were generated and sensitized to MHC class I antigens of the donor; (b) the generation of the CD8(+) CTLs required the help in vivo of CD4(+) cells, as well as priming with the allogeneic skin graft; and (c) the CD4(+) T helper cells were sensitized indirectly to donor peptides presented in association with class II antigens on recipient antigen-presenting cells. These results provide evidence that indirect recognition can provide effective help for CTL induction during graft rejection, even when the cytotoxic T cells are sensitized by determinants expressed only on the donor graft. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-18646, HL-36372]; NIAID NIH HHS [AI-21569] NR 25 TC 177 Z9 179 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 MAR 1 PY 1994 VL 179 IS 3 BP 865 EP 872 DI 10.1084/jem.179.3.865 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MY484 UT WOS:A1994MY48400010 PM 8113680 ER PT J AU PULIDO, R SCHLOSSMAN, SF SAITO, H STREULI, M AF PULIDO, R SCHLOSSMAN, SF SAITO, H STREULI, M TI IDENTIFICATION OF AMINO-ACIDS AT THE JUNCTION OF EXON-3 AND EXON-7 THAT ARE USED FOR THE GENERATION OF GLYCOSYLATION-RELATED HUMAN CD45RO AND CD45RO-LIKE ANTIGEN SPECIFICITIES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID LEUKOCYTE-COMMON ANTIGEN; HUMAN LYMPHOCYTES-T; PROTEIN TYROSINE KINASE; MONOCLONAL-ANTIBODIES; PHOSPHATASE-ACTIVITY; CELL LINES; EXPRESSION; PHOSPHORYLATION; A6 AB The CD45 transmembrane protein tyrosine phosphatase plays an essential role in lymphocyte activation. In humans, CD45 is composed of five isoforms that are generated by alternative splicing of three exons of a common precursor mRNA. Expression of the smallest molecular mass 180-kD CD45 isoform (CD45-O) results from splicing out of exons 4(A), 5(B), and 6(C), which encode peptide regions near the NH2 terminus, and is regulated during T cell maturation and activation. Two monoclonal antibodies (mAb), UCHL1 (anti-CD45RO) and A6 (anti-CD45RO-like), were studied that selectively bind to murine transfectant cells expressing the human CD45-0 isoform. The anti-CD45RO-like A6 mAb, but not the anti-CD45RO UCHL1 mAb, also weakly reacted with transfectant cells expressing the human CD45 isoforms that contained exons 4 and 5(AB), or exon 5(B) encoded sequences. The structural basis of the antigen specificities of these two different human anti-CD45RO mAbs was investigated at the molecular level by using potential glycosylation-defective CD45-0 isoform variants containing amino acid substitutions at the junction of exons 3 and 7. Replacement of the threonine residue at position 8 (last amino acid encoded in exon 3 and a putative O-linked carbohydrate anchorage site) by an alanine, completely abrogated the reactivity of the UCHL1 mAb, but did not affect that of the A6 mAb. Conversely, replacement of either the asparagine at position 174 or the serine at position 176 (the first two putative carbohydrate anchorage sites in exon 7) by alanine, abrogated the reactivity of the A6 mAb, but not that of the UCHL1 mAb. Both the UCHL1 and A6 epitopes were dependent on the presence of O-linked carbohydrates; and the UCHL1, but not the A6 epitope, was dependent on the presence of sialic acid. These results demonstrate a pivotal role for the amino acids encoded at the junction of exons 3 and 7 for the generation of glycosylation-related CD45RO epitopes that are expressed in a cell lineage- and activation-regulated fashion. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-55547]; NIAID NIH HHS [AI-26598] NR 25 TC 17 Z9 17 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 MAR 1 PY 1994 VL 179 IS 3 BP 1035 EP 1040 DI 10.1084/jem.179.3.1035 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MY484 UT WOS:A1994MY48400030 PM 7509359 ER PT J AU LEONG, GB AF LEONG, GB TI DECLERAMBAULT SYNDROME (EROTOMANIA) IN THE CRIMINAL-JUSTICE SYSTEM - ANOTHER LOOK AT THIS RECURRING PROBLEM SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE PSYCHIATRY; EROTOMANIA; DECLERAMBAULTS SYNDROME; DANGEROUSNESS; DELUSIONS ID LOVE AB While de Clerambault syndrome (crotomania) has long been a subject of scientific study, it has only recently become a frequent topic of media attention. A series of five individuals who were arrested for crimes related to their erotomanic delusion are presented. The psychiatric findings from this sample have potential social policy implication. C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. RP LEONG, GB (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIATRY SERV,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 19 TC 20 Z9 20 U1 1 U2 2 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 MAR PY 1994 VL 39 IS 2 BP 378 EP 385 PG 8 WC Medicine, Legal SC Legal Medicine GA ND048 UT WOS:A1994ND04800010 PM 8195752 ER PT J AU SALAZAR, M WILLIAMSON, J BING, DH AF SALAZAR, M WILLIAMSON, J BING, DH TI GENETIC TYPING OF THE DQA1-ASTERISK-4 ALLELES BY RESTRICTION ENZYME DIGESTION OF THE PCR PRODUCT OBTAINED WITH THE DQ-ALPHA-AMPLITYPE(TM) KIT SO JOURNAL OF FORENSIC SCIENCES LA English DT Note DE PATHOLOGY AND BIOLOGY; POLYMERASE CHAIN REACTION; DQ-ALPHA; RESTRICTION ENZYMES ID HLA-DQA1 AB The three DQ Alpha 4 alleles, 4.1 (0501), 4.2 (0401), and 4.3 (0601) cannot be distinguished with the reverse dot blot DQ Alpha Amplitype(TM) Kit. A previous report (Yunis, 1. et al., Tissue Antigens, Vol. 39, 1992, pp. 182-186) indicated that the typing of these three alleles can be accomplished by endonuclease digestion of the PCR product that is produced following amplification with the DQ Alpha primers with Fok I and Rsa 1. We report here the use of this method to type the DQA1*0401, 0501 and 0601 alleles in the PCR product obtained with the DQ Alpha-Amplitype(TM) Kit. We have analyzed the PCR product obtained in over 200 forensic samples. We have found that in all of these cases, it is possible to assign a type to those samples that type as DQ Alpha 4 with the Amplitype Kit. Furthermore, we have found the technique to be useful in some cases where it has not been previously possible to distinguish individuals or samples that have the DQ Alpha 4 allele and type identically with respect to all other DQ Alpha alleles. C1 CBR LABS INC,CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 7 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAR PY 1994 VL 39 IS 2 BP 518 EP 525 PG 8 WC Medicine, Legal SC Legal Medicine GA ND048 UT WOS:A1994ND04800025 PM 8195762 ER PT J AU MACKINNEY, AA AF MACKINNEY, AA TI ON TEACHING BEDSIDE DIAGNOSTIC AND THERAPEUTIC PROCEDURES TO MEDICAL-STUDENTS - AN ANNOTATED-BIBLIOGRAPHY OF AUDIOVISUAL MATERIALS SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Bibliography DE BEDSIDE PROCEDURES; MEDICAL STUDENTS; TEACHING; VIDEO-TAPES; AUDIOVISUAL MATERIALS AB Objective: The teaching of procedures that involve risk of pain or morbidity deserves special care. The author set out to develop a teaching program for medical students to ensure quality control of bedside diagnostic and therapeutic procedures. Design: A bibliography of available videotapes and related audiovisual teaching materials on 15 common bedside procedures was assembled following requests for materials from all U.S. medical schools. Audiovisual materials from nine institutions were reviewed. Setting: Medical schools and teaching institutions. Participants: Medical schools and libraries. Main results: Seventy-three percent (24/33) of responding schools had no visual material on the procedures. There was ten times more material on physical diagnosis than on bedside procedures. About 20 videotapes were reviewed in an annotated bibliography. Some videos contained valuable insights on how to make good teaching materials. A set of criteria for quality videotapes is listed. Conclusions: Considerable work needs to be done to develop audiovisual materials and curricula for teaching bedside procedures. Videotape is a valuable medium for introducing procedures and ensuring uniformity of technique. After reviewing all available videotapes, the author decided that videotapes should be the initial part of a multidimensional program for teaching procedures. RP MACKINNEY, AA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 1994 VL 9 IS 3 BP 153 EP 157 DI 10.1007/BF02600031 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA ND613 UT WOS:A1994ND61300006 PM 7515107 ER PT J AU ANDERS, EM HARTLEY, CA READING, PC EZEKOWITZ, RAB AF ANDERS, EM HARTLEY, CA READING, PC EZEKOWITZ, RAB TI COMPLEMENT-DEPENDENT NEUTRALIZATION OF INFLUENZA-VIRUS BY A SERUM MANNOSE-BINDING LECTIN SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SURFACTANT PROTEIN-D; BACTERICIDAL ACTIVITY; BOVINE CONGLUTININ; CLASSICAL PATHWAY; BETA-INHIBITORS; DISTINCT; RECOGNITION; ACTIVATION; RABBIT AB The nature of the P inhibitor in guinea-pig serum and its mechanism of neutralization of influenza virus have been investigated. This inhibitor was shown to be a mannose-binding lectin serologically related to human serum mannose-binding protein. Ca2+-dependent binding of the guinea-pig lectin to influenza virus or to mannan could be detected with polyclonal or monoclonal antibodies against human mannose-binding protein in an ELISA. Furthermore, the monoclonal antibody inhibited both the haemagglutination-inhibiting and virus-neutralizing activities of the guinea-pig lectin. The lectin was active against influenza viruses of both type A and type B. In haemagglutination inhibition it acts independently of complement, apparently by sterically hindering access to the receptor-binding site on the viral haemagglutinin through binding of the lectin to carbohydrate side-chains in the vicinity of this site. Neutralization by the lectin, however, was shown to require activation of the classical complement pathway. To our knowledge, the neutralization of influenza virus by a serum lectin plus complement represents a previously unrecognized mechanism of complement-dependent viral inactivation that may be important in first-line host defence against a variety of enveloped viruses. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. RP ANDERS, EM (reprint author), UNIV MELBOURNE,DEPT MICROBIOL,PARKVILLE,VIC 3052,AUSTRALIA. NR 46 TC 89 Z9 90 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAR PY 1994 VL 75 BP 615 EP 622 DI 10.1099/0022-1317-75-3-615 PN 3 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA MY789 UT WOS:A1994MY78900016 PM 8126457 ER PT J AU ARK, JW GELBERMAN, RH ABRAHAMSSON, SO SEILER, JG AMIEL, D AF ARK, JW GELBERMAN, RH ABRAHAMSSON, SO SEILER, JG AMIEL, D TI CELLULAR-SURVIVAL AND PROLIFERATION IN AUTOGENOUS FLEXOR TENDON CRAFTS SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB In order to investigate fibroblast survival and proliferation in autogenous flexor tendon grafts, hindlimb intrasynovial and extrasynovial donor tendons were placed within the synovial sheaths of the medial and lateral forepaw digits of 21 dogs (42 tendons) and treated with controlled early passive motion. Intravital histologic evaluations with confocal microscopy and biochemical determinations of total DNA content and DNA synthesis were carried out at 10 days, 3 weeks, and 6 weeks. Intravital staining of the extrasynovial tendon grafts demonstrated variable degrees of cellular necrosis at the earliest intervals followed by cellular repopulation with fibroblasts and neovascularization from surface vessels. In contrast, intrasynovial tendon grafts were populated predominantly by viable cells at each interval, with occasional patches of cell necrosis and fibroblast ingrowth. Total DNA content and DNA synthesis values in the intrasynovial donor tendons were significantly lower than those seen in the extrasynovial tendon grafts at each interval. Extrasynovial tendons appear to act as scaffolds, undergoing extensive cellular death followed by a rapid repair response. Findings that intrasynovial tendon fibroblasts survive the tendon grafting process suggest that the nutritional supplies and metabolic requirements of intrasynovial and extrasynovial donor tendons differ largely. RP ARK, JW (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,15 PARKMAN ST,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [5R01-AR33097] NR 0 TC 29 Z9 30 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 MAR PY 1994 VL 19A IS 2 BP 249 EP 258 DI 10.1016/0363-5023(94)90015-9 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA NJ837 UT WOS:A1994NJ83700015 PM 8201190 ER PT J AU ABRAHAMSSON, SO GELBERMAN, RH LOHMANDER, SL AF ABRAHAMSSON, SO GELBERMAN, RH LOHMANDER, SL TI VARIATIONS IN CELLULAR PROLIFERATION AND MATRIX SYNTHESIS IN INTRASYNOVIAL AND EXTRASYNOVIAL TENDONS - AN IN-VITRO STUDY IN DOGS SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB Intrasynovial and extrasynovial flexor tendon grafts recently have been shown to have dissimilar patterns of cellular survival and host integration within the digital sheath. in an effort to determine if fundamental differences exist between these two types of tendons, we investigated the biochemical composition and cellular activity of intrasynovial and extrasynovial tendon segments of 12 adult mongrel dogs in short-term explant culture in MCDB 105 and in DMEM media. Proteoglycan, collagen and noncollagen protein synthesis and content and DNA synthesis were determined following culture in both media. Intrasynovial tendon segments cultured in MCDB 105 medium synthesized significantly less collagen, noncollagen protein, and DNA and had similar amounts of proteoglycans compared to extrasynovial tendons. Comparison of intrasynovial and extrasynovial tendon segment responses in DMEM medium showed that intrasynovial tendons synthesized more proteoglycan, protein, and DNA than they did in MCDB 105. Extrasynovial tendons had similar rates of matrix component and DNA synthesis in both media. Findings that the synthesis of matrix components and DNA between intrasynovial flexor and extrasynovial peroneal tendon segments differ significantly indicate that intrasynovial flexor tendons may be specially adapted to the nutritional milieu provided by an intrasynovial environment. These data are supported by the selective successful stimulation of fibrocartilaginous segments within intrasynovial Flexor tendons in media favored for the culture of cartilaginous tissue. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. RI Lohmander, Stefan/I-8326-2012; OI Lohmander, Stefan/0000-0002-5424-9448 FU NIAMS NIH HHS [AR33097] NR 0 TC 31 Z9 31 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 MAR PY 1994 VL 19A IS 2 BP 259 EP 265 DI 10.1016/0363-5023(94)90016-7 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA NJ837 UT WOS:A1994NJ83700016 PM 8201191 ER PT J AU BELKIN, GS AF BELKIN, GS TI NUMBERS AND THE POLITICS OF HEALTH-CARE - INTRODUCTION SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Editorial Material RP BELKIN, GS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA BOX 90660, DURHAM, NC 27708-0660 SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD SPR PY 1994 VL 19 IS 1 BP 3 EP 5 DI 10.1215/03616878-19-1-3 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA NG433 UT WOS:A1994NG43300001 ER PT J AU DOYLE, KM BIRD, DA ALSALIHI, S HALLAQ, Y CLUETTEBROWN, JE GOSS, KA LAPOSATA, M AF DOYLE, KM BIRD, DA ALSALIHI, S HALLAQ, Y CLUETTEBROWN, JE GOSS, KA LAPOSATA, M TI FATTY-ACID ETHYL-ESTERS ARE PRESENT IN HUMAN SERUM AFTER ETHANOL INGESTION SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ALCOHOL; LIPOPROTEINS; ALBUMIN ID ADIPOSE-TISSUE; METABOLISM; IDENTIFICATION; ABSORPTION; SYNTHASE AB The aim of the study was to determine whether fatty acid ethyl esters, nonoxidative products of ethanol metabolism selectively present in organs damaged by ethanol abuse, are detectable in the serum after ethanol ingestion. Serum samples of hospital emergency room patients with positive (n = 32) and negative (n = 5) blood ethanol levels were assayed for fatty acid ethyl esters. In a separate study, five healthy subjects received an ethanol dose based on body weight mixed with fruit juice in a 1:2 ratio and administered by measured ingestion. Fatty acid ethyl esters were found in the serum of hospital emergency room patients with positive blood ethanol levels. The concentration of fatty acid ethyl esters in these patients correlated with the concentration of blood ethanol (r = 0.57; 95% confidence interval 0.28 to 0.77; P = 0.0002). In the controlled ethanol ingestion study with five healthy subjects, it was also determined that the serum fatty acid ethyl ester concentration began to decrease within 2 h of the time ethanol ingestion had been stopped. The fatty acid ethyl esters in the serum were bound to lipoprotein and albumin, and there was a higher percentage of saturated fatty acids in the FAEE pool than in the serum free fatty acid and triglyceride pools. These studies indicate that fatty acid ethyl esters, which have been implicated as mediators of ethanol-induced organ toxicity, are present in serum after ethanol ingestion. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIDDK NIH HHS [R01 DK37454, R01 DK43159] NR 20 TC 109 Z9 111 U1 0 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 1994 VL 35 IS 3 BP 428 EP 437 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NA036 UT WOS:A1994NA03600007 PM 8014578 ER PT J AU VELAMOOR, VR NORMAN, RMG CAROFF, SN MANN, SC SULLIVAN, KA ANTELO, RE AF VELAMOOR, VR NORMAN, RMG CAROFF, SN MANN, SC SULLIVAN, KA ANTELO, RE TI PROGRESSION OF SYMPTOMS IN NEUROLEPTIC MALIGNANT SYNDROME SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID CATATONIA; DANTROLENE AB The neuroleptic malignant syndrome (NMS) is a rare but potentially fatal disorder characterized by mental-status changes, muscle rigidity, hyperthermia, and autonomic dysfunction. Systematic examination of early signs and the progression of symptoms in NMS may be worthwhile to facilitate prompt recognition and interventions to abort the syndrome in its incipient stage. The authors present the results of a preliminary review of the temporal sequence of the four predominant signs of NMS as described in 340 clinical reports of NMS in the literature. Of all order implications, 70.5% were consistent with the sequence of mental-status changes, rigidity, hyperthermia, and autonomic dysfunction. Changes in either mental status or rigidity were the initial manifestations of NMS in 82.3% of cases with a single presenting sign and were significantly more Likely to be observed before hyperthermia and autonomic dysfunction. Methodological limitations of these data and clinical implications are discussed. C1 UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP VELAMOOR, VR (reprint author), VICTORIA HOSP,DEPT PSYCHIAT,375 SOUTH ST,LONDON N6A 4G5,ON,CANADA. NR 25 TC 70 Z9 72 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 1994 VL 182 IS 3 BP 168 EP 173 DI 10.1097/00005053-199403000-00007 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NA763 UT WOS:A1994NA76300007 PM 7906709 ER PT J AU BHIDE, PG WEST, WC FRY, KR FROST, DO AF BHIDE, PG WEST, WC FRY, KR FROST, DO TI AN IMMUNOCYTOCHEMICAL MARKER FOR HAMSTER RETINAL GANGLION-CELLS SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID LATERAL GENICULATE-NUCLEUS; DISPLACED AMACRINE CELLS; OPTIC-NERVE; MONOCLONAL-ANTIBODY; RABBIT RETINA; ADULT MICE; CAT RETINA; RAT RETINA; LAYER; TRANSECTION AB We examined the specificity and developmental time course of the labelling of retinal ganglion cells in Syrian hamsters by a monoclonal antibody AB5. In adult hamsters, AB5 selectively labelled somata in the ganglion cell layer, dendrites in the inner plexiform layer and axons in the nerve fibre layer. When retinal ganglion cells were retrogradely labelled with DiI prior to AB5 immunocytochemistry, all of the retrogradely labelled retinal ganglion cells in the ganglion cell layer were AB5 immunoreactive, indicating that AB5 labels all classes of ganglion cell in that layer. In retinae depleted of retinal ganglion cells by neonatal optic nerve transections, AB5 did not label any somata or processes, indicating that AB5 specifically labels retinal ganglion cells. During development, AB5 labelling first appeared as a weak staining of cell bodies in the ganglion cell layer on postnatal day 12 (P12; PO = first 24 h following birth) and acquired the staining pattern seen in the adult by postnatal day 14. From the onset of AB5 immunoreactivity, ABS-labelled somata of varying sizes were present across the entire retinal surface. Although AB5 labelled retinal ganglion cell axons in the nerve fibre layer of the retina it did not label the optic nerve or retinal ganglion cell axons in the brain at any age examined. AB5 labelling was also found to be compatible with bromodeoxyuridine immunocytochemistry and, therefore, useful for determining the time of generation of hamster retinal ganglion cells. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02114. TUFTS UNIV,DEPT PSYCHOL,MEDFORD,MA 02155. BAYLOR COLL MED,CTR BIOTECHNOL,ALICE R MCPHERSON LAB RETINA RES,THE WOODLANDS,TX 77381. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. FU NEI NIH HHS [EY-03465, EY-06469] NR 35 TC 2 Z9 2 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD MAR PY 1994 VL 23 IS 3 BP 167 EP 177 DI 10.1007/BF01181558 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA NB138 UT WOS:A1994NB13800002 PM 8006677 ER PT J AU SALLOWAY, S CUMMINGS, J AF SALLOWAY, S CUMMINGS, J TI SUBCORTICAL DISEASE AND NEUROPSYCHIATRIC ILLNESS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Editorial Material ID OBSESSIVE-COMPULSIVE DISORDER; BASAL GANGLIA; HUNTINGTONS-DISEASE; BEHAVIORAL-CHANGES; MOOD DISORDER; LESIONS; INFARCTION; DEPRESSION; SYMPTOMS; GLUCOSE AB The relationship between neuropsychiatric disorders and dysfunction of subcortical structures is the theme of the 1994 joint meeting of the British and American Neuropsychiatric Associations, to be held July 21-24, 1994, in Newport, Rhode Island. In this essay Dr. Salloway, chair of the Scientific Program Committee, and Dr. Cummings, director-elect of The American Neuropsychiatric Association, define the structures embraced in the ''subcortical'' concept and summarize the relationship between specific neuropsychiatric symptoms and regional subcortical dysfunction. These concepts and observations will be expanded, challenged, and refined at the meeting. C1 BUTLER HOSP, PROVIDENCE, RI 02906 USA. 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 VET AFFAIRS MED CTR, PSYCHIAT SERV, BEHAV NEUROSCI SECT, LOS ANGELES, CA USA. RP SALLOWAY, S (reprint author), BROWN UNIV, SCH MED, PROVIDENCE, RI 02912 USA. FU NIA NIH HHS [AG10123] NR 36 TC 36 Z9 36 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1994 VL 6 IS 2 BP 93 EP 99 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ963 UT WOS:A1994NJ96300001 PM 8044049 ER PT J AU AMES, D CUMMINGS, JL WIRSHING, WC QUINN, B MAHLER, M AF AMES, D CUMMINGS, JL WIRSHING, WC QUINN, B MAHLER, M TI REPETITIVE AND COMPULSIVE BEHAVIOR IN FRONTAL-LOBE DEGENERATIONS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID KLUVER-BUCY SYNDROME; NON-ALZHEIMER TYPE; PICKS DISEASE; BASAL GANGLIA; DIAGNOSIS; DEMENTIA; DISORDER AB The authors review the relationship of repetitive behaviors to frontal lobe degenerations and report the repetitive and compulsive behaviors, radiologic imaging findings, and neuropathology of 3 patients with dementia secondary to frontal lobe degeneration. These 3 patients and 78% of 46 proven pathologic cases of frontal lobe degeneration described in the literature demonstrate repetitive behaviors ranging from motor stereotypies to complex obsessive-compulsive disorder. This review suggests that combined damage to the frontal lobe, caudate nucleus, and globus pallidus may account for the repetitive behaviors seen in frontal lobe degenerations, idiopathic obsessive-compulsive disorder, and other neuropsychiatric diseases. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PATHOL, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PSYCHIAT & BIOBEHAV SCI, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, PSYCHIAT SERV, LOS ANGELES, CA USA. FU NIA NIH HHS [AG10123] NR 49 TC 86 Z9 86 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1994 VL 6 IS 2 BP 100 EP 113 PG 14 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ963 UT WOS:A1994NJ96300002 PM 8044031 ER PT J AU KOSTYK, SK DAMORE, PA HERMAN, IM WAGNER, JA AF KOSTYK, SK DAMORE, PA HERMAN, IM WAGNER, JA TI OPTIC-NERVE INJURY ALTERS BASIC FIBROBLAST GROWTH-FACTOR LOCALIZATION IN THE RETINA AND OPTIC TRACT SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BASIC FIBROBLAST GROWTH FACTOR; RETINA; OPTIC NERVE; OPTIC TRACT; FIBROBLAST GROWTH FACTORS; CNS INJURY; PHOTORECEPTORS; RAT; MOUSE; GLIAL CELLS ID PIGMENT EPITHELIUM INVITRO; GANGLION-CELLS; MESSENGER-RNA; OUTER SEGMENTS; LIGHT DAMAGE; BRAIN REGION; RAT-BRAIN; NEURONS; BFGF; PROLIFERATION AB Basic fibroblast growth factor (bFGF) is thought to be a trophic factor for several classes of neurons. Its distribution changes in response to cortical neural injury. We have determined the effect of injury to the optic nerve on localization of bFGF in the rodent retina and visual pathways. Our observations were confirmed by using different antisera and monoclonal antibodies. While photoreceptors normally contain virtually no bFGF, crushing the optic nerve causes a striking increase, over a period of several weeks, in the amount of bFGF in retinal photoreceptors. Since photoreceptors do not synapse directly upon the injured ganglion cells, intermediary cells must participate in the cascade of events that results in the elevated bFGF. In light of the observation that exogenous bFGF protects photoreceptors from photodamage (Faktorovich et al., 1992), this increase in bFGF in photoreceptors may explain, in part, why crushing the optic nerve protects photoreceptors against photodamage (Bush and Williams, 1991). Whereas bFGF is constitutively found in glia in the optic nerve, little bFGF is found in glia in the optic tract. However, damage to the optic nerve increases bFGF in astrocytes in the optic tract. This change occurs within days, suggesting that a relatively direct signal may intervene between the injured axon and the adjacent glial cells. Thus, despite the fact that the optic nerve and optic tract are contiguous structures through which axons of retinal ganglion cells project, the glial elements in these structures express distinct properties, because of differences in either glial subclasses or microenvironment. We suggest that changes in neuronal and glial bFGF expression are part of a coordinated injury response that involves a dynamic interaction between neural cells and trophic factors. These changes may contribute to either a beneficial regenerative response or a pathological change that inhibits regeneration. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. TUFTS UNIV,SCH HLTH SCI,PROGRAM CELL MOLEC & DEV BIOL,BOSTON,MA 02111. CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,DEPT CELL BIOL & ANAT,NEW YORK,NY 10021. CHILDRENS HOSP,DEPT SURG RES,BOSTON,MA 02114. FU NEI NIH HHS [5 K11 EY00311, EY06454, EY09033] NR 64 TC 90 Z9 94 U1 2 U2 4 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 MAR PY 1994 VL 14 IS 3 BP 1441 EP 1449 PN 2 PG 9 WC Neurosciences SC Neurosciences & Neurology GA MZ407 UT WOS:A1994MZ40700006 PM 7510332 ER PT J AU FREEMAN, GL COLSTON, JT MILLER, DD AF FREEMAN, GL COLSTON, JT MILLER, DD TI ALTERATIONS IN MYOCARDIAL FREE FATTY-ACID CLEARANCE PRECEDE MECHANICAL ABNORMALITIES IN CANINE TACHYCARDIA-INDUCED HEART-FAILURE SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE ENERGETICS; MYOCARDIAL; DEPRESSION; CONTRACTILITY; CARDIAC METABOLISM ID CHRONIC SUPRAVENTRICULAR TACHYCARDIA; I-123 PHENYLPENTADECANOIC ACID; CONGESTIVE CARDIOMYOPATHY; HYPERTENSIVE RATS; PRESSURE; DOGS; TOMOGRAPHY; INJURY; TRACER AB Background. The purpose of this study was to evaluate whether abnormalities of free fatty acid metabolism are present before the onset of overt mechanical dysfunction in dogs with tachycardia-induced heart failure. We studied six dogs chronically instrumented to allow assessment of left ventricular function in the pressure-volume plane. Methods and Results. Free fatty acid clearance was assessed according to the washout rate of a free fatty acid analog, iodophenylpentadecanoic acid ([I-123]PPA or IPPA). IPPA clearance was measured within 1 hour of the hemodynamic assessment, The animals were studied under baseline conditions and 11.7 +/- 3.6 days after ventricular pacing at a rate of 240 beats/min. Hemodynamic studies after pacing showed a nonsignificant increase in left ventricular end-diastolic pressure (11.7 +/- 4.7 to 17.4 +/- 6.5 mm Hg) and a nonsignificant decrease in the maximum derivative of pressure with respect to time (1836 +/- 164 vs 1688 +/- 422 mm Hg/sec). There was also no change in the time constant of left ventricular relaxation, which was 34.8 +/- 7.67 msec before and 35.3 +/- 7.3 msec after pacing. However, a significant prolongation in the clearance half-time of [I-123]PPA, from 86.1 +/- 23.9 to 146.5 +/- 22.6 minutes (p < 0.01) was found. Thus abnormal lipid clearance appears before the onset of significant mechanical dysfunction in tachycardia-induced heart failure. Conclusion. This suggests that abnormal substrate metabolism may play an important role in the pathogenesis of this condition. C1 ST LOUIS UNIV,CTR HLTH SCI,DEPT MED,DIV CARDIOL,ST LOUIS,MO 63110. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CARDIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 25 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 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD MAR-APR PY 1994 VL 1 IS 2 BP 171 EP 179 DI 10.1007/BF02984089 PN 1 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA PU845 UT WOS:A1994PU84500007 PM 9420684 ER PT J AU ENTZIAN, W ARONOW, S SOLOWAY, AH SWEET, WH AF ENTZIAN, W ARONOW, S SOLOWAY, AH SWEET, WH TI A PRELIMINARY EVALUATION OF FLUORINE-18-LABELED TETRAFLUOROBORATE AS A SCANNING AGENT FOR INTRACRANIAL TUMORS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Note C1 UNIV BONN,NEUROCHIRURG KLIN,W-5300 BONN,GERMANY. RP ENTZIAN, W (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 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 MAR PY 1994 VL 35 IS 3 BP 424 EP 424 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MZ747 UT WOS:A1994MZ74700010 ER PT J AU ELMALEH, DR LIVNI, E ALPERT, NM STRAUSS, HW BUXTON, R FISCHMAN, AJ AF ELMALEH, DR LIVNI, E ALPERT, NM STRAUSS, HW BUXTON, R FISCHMAN, AJ TI MYOCARDIAL EXTRACTION OF 1-[C-11]BETAMETHYLHEPTADECANOIC ACID SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE FATTY ACIDS; MYOCARDIUM; PET; BETAMETHYLHEPTADECANOIC ACID; METABOLISM ID POSITRON-EMISSION TOMOGRAPHY; CORONARY-ARTERY DISEASE; NON-INVASIVE EVALUATION; LABELED PALMITIC ACID; COMPUTED-TOMOGRAPHY; FATTY-ACIDS; EXTERNAL ASSESSMENT; METABOLISM; HEART; INVIVO AB Betamethylheptadecanoic acid (BMHA) is a branched chain fatty acid analog that is transported into myocardial cells by the same long chain fatty acid carrier protein mechanism as natural fatty acids, but cannot be completely catabolized and accumulates in the tissue. Thus, C-11-labeled BMHA is a useful tracer for the noninvasive evaluation of myocardial fatty acid utilization by positron emission tomography (PET). Methods: As a prelude to PET studies, the metabolism of BMHA was studied by classical techniques. We measured the net extraction fraction (E(n)) of 1-[C-11]-beta-R,S-methylheptadecanoic acid (1-[C-11]BMHA) and compared it to that of natural fatty acids in dogs, using arterial/venous measurements and a mathematical model. Two groups of conditioned dogs were studied. In the first group, measurements were made under fasting (normal control) conditions and in the second group, measurements were made during glucose and insulin infusion. Myocardial blood flow, and the extraction/utilization of other substrates (glucose, oxygen and lactate) were also measured. Results: For natural fatty acids in the basal state, E(n)(FA) was 0.335. After glucose/insulin infusion, this value decreased to 0.195. The 1-[C-11]BMHA showed a similar decrease in E(n)(BMHA) from 0.220 in the control group to 0.100 in the group treated with glucose/insulin infusion. Preliminary PET studies with 1-[C-11]BMHA verified the validity of performing these measurements noninvasively. Conclusion: The results of these studies indicate that rates of fatty acid metabolism in the myocardium can be determined from steady-state concentrations of 1-[C-11]BMHA. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [1 R01 HL 39587-01] NR 36 TC 11 Z9 11 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 MAR PY 1994 VL 35 IS 3 BP 496 EP 503 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MZ747 UT WOS:A1994MZ74700030 PM 8113905 ER PT J AU ERICKSON, K LIANG, LL SHUM, P NATHANSON, JA AF ERICKSON, K LIANG, LL SHUM, P NATHANSON, JA TI ADRENERGIC REGULATION OF AQUEOUS OUTFLOW SO JOURNAL OF OCULAR PHARMACOLOGY LA English DT Article AB Epinephrine increased outflow facility and cyclic AMP in the in vitro perfused human anterior segment with a maximal facility increase of 44% occurring at approximately 2 x 10(-5) M. Cyclic AMP measured in the perfusate from anterior segments increased by 12 - 14 fold after administration of 10(-5) M epinephrine. Both the facility increase and cyclic AMP rise were blocked by the beta-2 selective antagonist, ICI118,551. While there was a correlation between the facility increase and elevation in cyclic AMP levels, the rise in cyclic AMP preceded the facility increase by about 1 hour, suggesting that the ultimate effect of epinephrine involved a rather slow event such as synthesis and release of prostaglandins or protein synthesis. Subsequent perfusion studies showed that very large concentrations of indomethacin were necessary to block the outflow facility effect of epinephrine, suggesting that prostaglandin synthesis did not underlie the facility effect in this system. However, 5 x 10(-5) M cyclohexamide blocked the effect on outflow facility of both epinephrine and forskolin, but did not block the rise in cyclic AMP. These studies suggest that protein synthesis may play a role in the epinephrine-induced facility increase at some point beyond the second messenger level. RP ERICKSON, K (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY 07321] NR 0 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 8756-3320 J9 J OCUL PHARMACOL PD SPR PY 1994 VL 10 IS 1 BP 241 EP 252 DI 10.1089/jop.1994.10.241 PG 12 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA NE695 UT WOS:A1994NE69500021 PM 7911501 ER PT J AU FISHMAN, SM CARR, DB BECKETT, A ROSENBAUM, JF AF FISHMAN, SM CARR, DB BECKETT, A ROSENBAUM, JF TI HYPERCAPNIC VENTILATORY RESPONSE IN PATIENTS WITH PANIC DISORDER BEFORE AND AFTER ALPRAZOLAM TREATMENT AND IN PREMENSTRUAL AND POSTMENSTRUAL WOMEN SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID DIOXIDE-INDUCED ANXIETY; CARBON-DIOXIDE; INHALATION AB We tested the ventilatory and anxiety response to hypercapneic (CO2) challenge in women with panic disorder as well as in normal women in the premenstrual phase and mid-points of their menstrual cycles. Panic disorder patients were challenged on two occasions. each time while in the premenstrual phase of the menstrual cycle. receiving an open trial of alprazolam through the intervening 8 weeks between tests. This study confirms previous reports indicating increased sensitivity to CO2 in patients with panic disorder and that this sensitivity can be attenuated by treatment. We found a significant decrease in the ventilatory response of panic disorder patients comparing pre- and post-therapy. We also observed that normal females, while in the premenstrual phase of their menstrual cycle, have a heightened anxiety response to CO2 challenge. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ANALGES PEPTIDE RES UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CLIN PSYCHOPHARMACOL CLIN,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. RP FISHMAN, SM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH,CTR PAIN,BOSTON,MA 02114, USA. NR 16 TC 18 Z9 18 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAR-APR PY 1994 VL 28 IS 2 BP 165 EP 170 DI 10.1016/0022-3956(94)90027-2 PG 6 WC Psychiatry SC Psychiatry GA NP528 UT WOS:A1994NP52800006 PM 7932278 ER PT J AU BIEDERMAN, J LAPEY, KA MILBERGER, S FARAONE, SV REED, ED SEIDMAN, LJ AF BIEDERMAN, J LAPEY, KA MILBERGER, S FARAONE, SV REED, ED SEIDMAN, LJ TI MOTOR PREFERENCE, MAJOR DEPRESSION AND PSYCHOSOCIAL DYSFUNCTION AMONG CHILDREN WITH ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article ID PATHOLOGICAL LEFT-HANDEDNESS; LA-TOURETTES SYNDROME; LEARNING-DISABILITIES; PERCEPTUAL ASYMMETRY; PSYCHIATRIC-PATIENTS; GENETIC-RELATIONSHIP; RIGHT-HEMISPHERE; HAND PREFERENCE; INCREASED RISK; DYSLEXIA AB Since left motor preference has been hypothesized to lead to increased risk for psychopathology and cognitive deficits, it is possible that it may confer greater vulnerability for these problems to attention deficit hyperactivity disorder (ADHD) children. Subjects were 6-17 year-old boys with DSM-III-R ADHD (N = 140) and normal controls (N = 120) and their first-degree relatives. Information on motor preference was obtained in a standardized manner blind to the proband's clinical status. Although no excess of non-right motor preference was identified in ADHD probands compared with normal controls, the non-right motor preference observed in ADHD probands was partly familial and was associated with significantly increased risk for major depressive disorder and impaired psychosocial functioning. Non-right motor preference in ADHD probands significantly increases the risk for major depression and impaired psychosocial functioning. These findings raise the possibility of alterations in cerebral dominance which may be implicated in the expression of specific problems in some patients with ADHD. Further research is needed to replicate these findings and to directly assess cerebral functioning in ADHD. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [NIMH RO1 MH-41314-01A2] NR 51 TC 14 Z9 14 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAR-APR PY 1994 VL 28 IS 2 BP 171 EP 184 PG 14 WC Psychiatry SC Psychiatry GA NP528 UT WOS:A1994NP52800007 PM 7932279 ER PT J AU JOKHI, PP KING, A JUBINSKY, PT LOKE, YW AF JOKHI, PP KING, A JUBINSKY, PT LOKE, YW TI DEMONSTRATION OF THE LOW-AFFINITY ALPHA-SUBUNIT OF THE GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR-RECEPTOR (GM-CSF-R-ALPHA) ON HUMAN TROPHOBLAST AND UTERINE CELLS SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE GM-CSF RECEPTOR; IMMUNOHISTOCHEMISTRY; FLOW CYTOMETRY; HUMAN TROPHOBLAST; MACROPHAGES; GLANDS ID PLACENTAL CONDITIONED MEDIUM; EXTRAVILLOUS TROPHOBLAST; GRANULAR LYMPHOCYTES; HUMAN-ENDOMETRIUM; INTERFERON-GAMMA; GROWTH; EXPRESSION; PROLIFERATION; INVITRO; LYMPHOKINES AB Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a classical haematopoietic cytokine which has also been implicated in placental growth and development. In this study we have performed a detailed immunohistological localization of the low affinity GM-CSF receptor (GM-CSF-R alpha) in human first trimester implantation site and non-pregnant endometrium, We have also investigated receptor expression and GM-CSF binding in vitro by normal first trimester trophoblast using flow cytometric analysis and compared this with JEG-3 and JAR choriocarcinoma cells. In the first trimester, the GM-CSF-R was found to be present on villous cytotrophoblast and all populations of extravillous trophoblast. Expression by villous syncytiotrophoblast was weak or absent, but this increased markedly by term. GM-CSF-R were also expressed by fetal Hofbauer cells within the mesenchyme of the chorionic villi and by uterine glandular epithelium and decidual macrophages within maternal decidua. GM-CSF-R was not expressed by glands in proliferative phase endometrium but began to appear during the secretory phase, suggesting hormonal regulation of the receptor on uterine glandular epithelium. Flow cytometric comparison of normal isolated first trimester trophoblast and JEG-3 and JAR choriocarcinoma cells revealed two- to threefold higher surface expression of GM-CSF-R by choriocarcinoma cells and higher binding capacity for rhGM-CSF than normal trophoblast. These results suggest that GM-CSF may regulate growth and development of human trophoblast. GM-CSF may also influence placental development and function by acting via decidual and fetal macrophages, and uterine glandular epithelium, which are the other cell populations to express the receptor. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP JOKHI, PP (reprint author), UNIV CAMBRIDGE,DEPT PATHOL,DIV CELLULAR & GENET PATH,HUMAN REPROD IMMUNOBIOL RES GRP,CAMBRIDGE CB2 1QP,ENGLAND. FU Wellcome Trust NR 42 TC 43 Z9 43 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD MAR PY 1994 VL 26 IS 2 BP 147 EP 164 DI 10.1016/0165-0378(94)90037-X PG 18 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA NQ276 UT WOS:A1994NQ27600005 PM 7932390 ER PT J AU WILENS, TE BIEDERMAN, J SPENCER, T AF WILENS, TE BIEDERMAN, J SPENCER, T TI CLONIDINE FOR SLEEP DISTURBANCES ASSOCIATED WITH ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Note ID CHILDREN C1 MASSACHUSETTS GEN HOSP,CLIN & RES PROGRAM PEDIAT PSYCHOPHARMACOL,BOSTON,MA 02114. HARVARD UNIV,MCLEAN HOSP,SCH MED,BELMONT,MA 02178. NR 10 TC 52 Z9 53 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 MAR-APR PY 1994 VL 33 IS 3 BP 424 EP 426 DI 10.1097/00004583-199403000-00018 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA MY114 UT WOS:A1994MY11400018 PM 8169189 ER PT J AU GRAVENSTEIN, S DRINKA, P DUTHIE, EH MILLER, BA BROWN, CS HENSLEY, M CIRCO, R LANGER, E ERSHLER, WB AF GRAVENSTEIN, S DRINKA, P DUTHIE, EH MILLER, BA BROWN, CS HENSLEY, M CIRCO, R LANGER, E ERSHLER, WB TI EFFICACY OF AN INFLUENZA HEMAGGLUTININ DIPHTHERIA TOXOID CONJUGATE VACCINE IN ELDERLY NURSING-HOME SUBJECTS DURING AN INFLUENZA OUTBREAK SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ANTIBODY-RESPONSE; INTERLEUKIN-2 PRODUCTION; MORTALITY; AGE; IMMUNOGENICITY; REACTOGENICITY; PREVENTION; AMANTADINE; POPULATION; REDUCTION AB Objective: To compare the efficacy of an influenza hemagglutinin-diphtheria toroid conjugate vaccine with the commercially available influenza hemagglutinin-subunit vaccine in preventing influenza in older adults living in a nursing home. Design: A prospective, randomized, double-blind vaccine trial with 5 months of follow-up after vaccination. Setting: Fourteen Wisconsin nursing homes. Participants: Nursing home residents at least 65 years old who were able to give informed consent and were free of malignancy and not receiving immunosuppressive therapy. Interventions: Participants received, by intramuscular injection, 0.5 mt of a trivalent influenza vaccine containing 15 mu g each of A/Leningrad/360/86 (H3N2), A/Taiwan/1/86 (H1N1), and B/Ann Arbor/1/86 (HA) or 0.5 mt of an influenza vaccine containing the same antigens conjugated to diphtheria toroid (HA-D). Measurements: Blood was obtained pre- and 1 month postvaccination to assess for any vaccine-induced antibody titer change. Clinical surveillance for respiratory illness was performed twice weekly for 5 months. A record was kept of all signs and symptoms of new respiratory illness, and a viral culture and acute and convalescent sera were obtained. Results: 204 participants received HA and 204 received HA-D. Both groups had similar baseline antibody levels to all influenza antigens. HA-D recipients seroconverted more frequently based on serum neutralizing activity (P < 0.05), had a greater increase in geometric mean titer (GMT), and sustained the increase in antibody titer longer than HA recipients. Vaccine hemagglutinin recall was greater in a subset of HA-D recipients as measured by lymphocyte proliferative assays (P < 0.05). During an outbreak of influenza A (H3N2 A/Shanghai/11/87-like and A/Victoria/7/87-like), fewer HA-D (29/195) than HA (43/204) recipients had laboratory-confirmed infection (P = 0.053), and, of these, fewer HA-D-treated subjects had lower respiratory tract involvement (5/29 HA-D and 17/43 HA) (P = 0.022). Conclusions: HA-D was more immunogenic in institutionalized elderly recipients and produced greater protection from influenza infection. Superior protection may be due to HA-D's ability to stimulate and recruit antigen-presenting cells, thus enabling the recipient to achieve and maintain functional antibody titers. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. WISCONSIN VET HOME,KING,WI. MED COLL WISCONSIN,MILWAUKEE,WI. ZABLOCKI VET ADM MED CTR,MILWAUKEE,WI. WISCONSIN STATE LAB HYG,MADISON,WI. CONNAUGHT LABS LTD,SWIFTWATER,PA. RP GRAVENSTEIN, S (reprint author), UNIV WISCONSIN,DEPT MED,INST AGING & ADULT LIFE,GERIATR SECT,1300 UNIV AVE,ROOM 2245,MADISON,WI 53706, USA. RI Gravenstein, Stefan/G-1681-2011 FU NIA NIH HHS [AG 09632, AG 007831, AG 00548] NR 31 TC 79 Z9 81 U1 0 U2 2 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 MAR PY 1994 VL 42 IS 3 BP 245 EP 251 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NA038 UT WOS:A1994NA03800002 PM 8120307 ER PT J AU MAHONEY, J SAGER, M DUNHAM, NC JOHNSON, J AF MAHONEY, J SAGER, M DUNHAM, NC JOHNSON, J TI RISK OF FALLS AFTER HOSPITAL DISCHARGE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID HIP FRACTURE; ELDERLY PEOPLE; COMMUNITY; STRENGTH; DELIRIUM; HOME AB Objectives: To determine the incidence of falls within the first month after hospitalization and risk factors associated with falling during this period. Design: Cohort study with 1-month follow-up after hospital discharge. Setting: 370-bed community hospital. Patients: Consecutive sample of 214 patients, aged 70 years and over, hospitalized for medical illness more than 48 hours and discharged to the community. Exclusion criteria: terminal illness, neurologic diagnosis, discharge to skilled nursing facility. Measurements: Information was obtained at hospital admission, discharge, and 1 month after discharge. Initial assessment included demographic data, vision, mood, pre-admission function, and use of assistive device. Discharge assessment included length of hospital stay, use of assistive device, need for professional help after discharge, medications, cognition, and functional status. Patients were assessed 1 month after discharge for history of confusion and falls. Main outcome measure was falls in the first month after discharge. Main Results: Twenty-nine patients (13.6%) fell during the month after discharge. Major risk factors for falls included, at discharge, decline in mobility (P = 0.005), use of assistive device (P = 0.002), and cognitive impairment (P = 0.05), and after hospital discharge, self-report of confusion (P = 0.002). Patients who were functionally dependent and needed professional help after discharge had the highest rate of falls (20.2%). In contrast, only 8.4% of independent patients not requiring professional help fell (P = 0.01). Conclusions: There is a high incidence of falls after hospital discharge, particularly among patients who are functionally dependent. Further study is needed to determine to what extent acute illness and hospitalization may influence falls risk. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI. UNIV WISCONSIN,DEPT PREVENT MED,MADISON,WI. HOME HLTH UNITED,MADISON,WI. RP MAHONEY, J (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,GRECC,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NIA NIH HHS [1T32AG00213-02] NR 43 TC 95 Z9 97 U1 0 U2 6 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 MAR PY 1994 VL 42 IS 3 BP 269 EP 274 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NA038 UT WOS:A1994NA03800006 PM 8120311 ER PT J AU CHIODO, LK KANTEN, DN GERETY, MB MULROW, CD CORNELL, JE AF CHIODO, LK KANTEN, DN GERETY, MB MULROW, CD CORNELL, JE TI FUNCTIONAL STATUS OF MEXICAN-AMERICAN NURSING-HOME RESIDENTS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article AB Objective: To compare sociodemographic characteristics, physical function, and cognition of Mexican American and non-Hispanic white nursing home residents. Design and Setting: Cross-sectional survey of residents in eight proprietary nursing homes and one Veterans Affairs nursing home in San Antonio, Texas. Subjects: Residents with lengths of stay greater than or equal to 90 days. Measurements: Sociodemographic characteristics, residence prior to admission, and dependency in activities of daily living (ADL) were abstracted from the medical record. The Folstein Mini-Mental State Examination (MMSE) was administered in the resident's self-selected language to a subset of residents. Main Results: There were 1160 participants, 261 Mexican American (23%) and 899 non-Hispanic white residents (77%). Mexican Americans were younger (77.1 vs 80.7 years), more often men (44% vs 30%), less educated (6.2 vs 10.8 years), and more often dependent on Medicaid funding (66% vs 40%) than non-Hispanic whites. Mexican Americans were less independent in feeding (34% vs 49%), transfers (18% vs 30%), toileting (19% vs 29%), and dressing (12% vs 19%). Mean MMSE scores were different in Mexican Americans and non-Hispanic whites (8.93 vs 11.85), and this difference remained significant after adjustment for age and education (P = 0.04). ADL function was strongly associated with MMSE (P = 0.0001) and less strongly associated with ethnicity (P = 0.056) in multiple regression analysis. Conclusions: This study provides the strongest evidence to date that Mexican American nursing home residents are more cognitively and functionally impaired than non-Hispanic white residents. Further studies should explore whether medical conditions, selection and referral patterns or cultural factors explain functional differences between Mexican American and non-Hispanic white nursing home residents. C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DIV GEN MED,SAN ANTONIO,TX. RP CHIODO, LK (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU PHS HHS [NIA U01A09117-01] NR 11 TC 19 Z9 19 U1 0 U2 1 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 MAR PY 1994 VL 42 IS 3 BP 293 EP 296 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NA038 UT WOS:A1994NA03800010 PM 8120314 ER PT J AU CHUEH, HC BARNETT, GO AF CHUEH, HC BARNETT, GO TI CLIENT-SERVER, DISTRIBUTED DATABASE STRATEGIES IS A HEALTH-CARE RECORD SYSTEM FOR A HOMELESS POPULATION SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID INFORMATION; USERS AB Objective: To design and develop a computer-based health-care record system to address the needs of the patients and providers of a homeless population. Design: A computer-based health-care record system being developed for Boston's Healthcare for the Homeless Program (BHCHP) uses client-server technology and distributed database strategies to provide a common medical record for this transient population. The differing information requirements of physicians, nurses, and social workers are specifically addressed in the graphic application interface to facilitate an integrated approach to health care. This computer-based record system is designed for remote and portable use to integrate smoothly into the daily practice of providers of care to the homeless. The system uses remote networking technology and regular phone lines to support multiple concurrent users at remote sites of care. Results: A stand-alone, pilot system is in operation at the BHCHP medical respite unit. Information on 129 patient encounters from 37 unique sites has been entered. A full client-server system has been designed. Benchmarks show that while the relative performance of a communication link based upon a phone line is 0.07 to 0.15 that of a local area network, optimization permits adequate response. Conclusion: Medical records access in a transient population poses special problems. Use of client-server and distributed database strategies can provide a technical foundation that provides a secure, reliable, and accessible computer-based medical record in this environment. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP CHUEH, HC (reprint author), MASSACHUSETTS GEN HOSP,COMP SCI LAB,50 STANIFORD ST ,5TH FLOOR,BOSTON,MA 02114, USA. FU NLM NIH HHS [1 T15 LM07092] NR 25 TC 12 Z9 12 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 1994 VL 1 IS 2 BP 186 EP 198 PG 13 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 QA940 UT WOS:A1994QA94000009 PM 7719799 ER PT J AU LEE, R MITCHELL, JD GARAN, H RUSKIN, JN MCGOVERN, BA BUCKLEY, MJ TORCHIANA, DF VLAHAKES, GJ AF LEE, R MITCHELL, JD GARAN, H RUSKIN, JN MCGOVERN, BA BUCKLEY, MJ TORCHIANA, DF VLAHAKES, GJ TI OPERATION FOR RECURRENT VENTRICULAR-TACHYCARDIA - PREDICTORS OF SHORT-TERM AND LONG-TERM EFFICACY SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID SEQUENTIAL ENDOCARDIAL RESECTION; SUBENDOCARDIAL RESECTION; MYOCARDIAL-INFARCTION; MANAGEMENT; ARRHYTHMIAS; SELECTION; SURGERY; DEFIBRILLATOR; ORIGIN; SITE AB The success of ventricular operation in ablating drug-refractory ventricular tachycardia secondary to ischemic heart disease varies with surgical technique, the presence of certain identified risk factors, and patient selection biases. Forty-eight patients with drug-refractory ventricular tachycardia secondary to ischemic heart disease underwent directed ventricular operation. Ah patients had previous myocardial infarction, and 46 of 48 patients had a left-ventricular aneurysm. Mapping was done in 81% of patients. Patients underwent a combination of subendocardial resection, aneurysmectomy, and cryoablation. The operative mortality rate was 8%. Age greater than 65 years was the only risk factor for operative mortality. Forty-one patients underwent postoperative programmed electrical stimulation. In 26 patients (63%) tachycardia was noninducible, whereas it was inducible in 15 patients (37%). Stepwise logistic regression identified septal and inferior focus location as the most significant predictors of outcome. Septal focus location was a significant (p = 0.008) predictor of surgical success whereas inferior focus location was a significant (p = 0.015) predictor of surgical failure. Other identified independent risk factors for surgical failure were (1) use of cardioplegia, (2) lack of a completed intraoperative endocardial map, and (3) decreased ejection fraction. This generated model to predict success or failure had a sensitivity of 93.3% and a specificity of 92.4%. The success of ventricular operation is affected by the presence of certain risk factors. In the management of those patients at high risk for failure, other surgical options such as the placement of implantable cardioverter-defibrillator electrode patches at the time of ventricular operation or the alternative placement of a palliative implantable cardioverter-defibrillator should be considered. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,CARDIAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 27 TC 19 Z9 19 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 MAR PY 1994 VL 107 IS 3 BP 732 EP 742 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA NA898 UT WOS:A1994NA89800010 PM 8127103 ER PT J AU SHERIDAN, RL TOMPKINS, RG MCMANUS, WF PRUITT, BA AF SHERIDAN, RL TOMPKINS, RG MCMANUS, WF PRUITT, BA TI INTRACOMPARTMENTAL SEPSIS IN BURN PATIENTS SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID CHRONIC COMPARTMENT SYNDROME; FASCIOTOMY; DIAGNOSIS; ISCHEMIA; CATHETER; PRESSURE AB An uncommon cause of sepsis in patients with large burns is occult intracompartmental infection. A multi-institution review of 1171 burn admissions identified 5 patients (0.4%) who developed intracompartmental sepsis presenting with fever and purulent drainage or fever, erythema, and swelling on clinical examination. Contributing factors may have included high-volume resuscitation, delayed escharotomy, extravasated intraosseous infusion, cannulation-related arterial injury, and splinting or positioning difficulties. A high index of suspicion and an aggressive surgical approach facilitate successful management of this unusual problem. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. UNIV TEXAS, HLTH SCI CTR, USA INST SURG RES, SAN ANTONIO, TX USA. UNIFORMED SERV UNIV HLTH SCI, FT SAM HOUSTON, TX USA. RP SHERIDAN, RL (reprint author), MASSACHUSETTS GEN HOSP, SHRINERS BURNS INST, 51 BLOSSOM ST, BOSTON, MA 02114 USA. NR 49 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAR PY 1994 VL 36 IS 3 BP 301 EP 305 DI 10.1097/00005373-199403000-00003 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA NC960 UT WOS:A1994NC96000003 PM 8145308 ER PT J AU ZIETMAN, AL COEN, JJ SHIPLEY, WU WILLETT, CG EFIRD, JT AF ZIETMAN, AL COEN, JJ SHIPLEY, WU WILLETT, CG EFIRD, JT TI RADICAL RADIATION-THERAPY IN THE MANAGEMENT OF PROSTATIC ADENOCARCINOMA - THE INITIAL PROSTATE-SPECIFIC ANTIGEN VALUE AS A PREDICTOR OF TREATMENT OUTCOME SO JOURNAL OF UROLOGY LA English DT Article DE ANTIGENS; NEOPLASM; PROSTATIC NEOPLASMS; ADENOCARCINOMA; RADIOTHERAPY ID CANCER AB We studied 161 prostate cancer patients treated by radical irradiation alone without endocrine therapy in whom pretreatment and posttreatment prostate specific antigen (PSA) values were measured, and who had a minimum followup of 2 years. Outcome was analyzed in an actuarial fashion using clinical disease-free survival and biochemical disease-free survival (freedom from an increasing PSA level or a PSA level of greater than 1.0 ng./ml. 2 years following irradiation) as end points. Of the patients 54% achieved a post-irradiation nadir value in the range 0 to 1.0 ng./ml. and 29% had a nadir value that was undetectably low (less than 0.5 ng./ml.). The likelihood of achieving these values was greater among patients with early stage than locally advanced tumors. For all T stages the likelihood of being disease-free at 4 years was substantially and significantly lower when PSA was used as an end point than when clinical evaluation alone was used: stages T1 and T2 (85 patients) 41% versus 71%, and stages T3 and T4 (76 patients) 15% versus 61%. For the whole group at 4 years clinical control was 67% but biochemical control was only 26% (p < 0.05). The likelihood of being free of biochemical evidence of persistent disease at 4 years was a function of the initial PSA value (PSA less than 4.0 in 81% of the cases, 4.1 to 10.0 in 43%, 10.1 to 20.0 in 31%, 20.1 to 50.0 in 6% and greater than 50.0 in 0%). For stages T1 and T2 cancer patients with an initial PSA level of less than 15 ng./ml. (67% of all early stage cases) this value was 65% and it was even higher (73%) when poorly differentiated tumors were excluded. When the initial PSA level for stages T1 and T2 tumors was greater than 15 ng./ml. the projected 4-year rate of freedom from biochemical failure was only 7%. For stages T3 and T4 cancer patients the corresponding figures were 39% for those with an initial PSA level of less than 15 ng./ml. and 0% for those with an initial PSA level of greater than 15 ng./ml. The prognostic power of the initial PSA level was independent of stage, grade, patient age and prior transurethral resection of the prostate in a multivariate analysis. An initial serum PSA level of more than 15 ng./ml. is, therefore, a powerful predictor of probable failure with conventional radiation therapy. Serum PSA monitoring is a sensitive detector of early relapse. Knowledge of both will, in the future, allow the selection of patients for more intensive initial therapy or for early salvage. RP ZIETMAN, AL (reprint author), MASSACHUSETTS GEN HOSP,HARVARD SCH MED,DEPT RADIAT ONCOL,GENITO-URINARY ONCOL UNIT,BOSTON,MA 02114, USA. NR 18 TC 162 Z9 163 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 MAR PY 1994 VL 151 IS 3 BP 640 EP 645 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA MW725 UT WOS:A1994MW72500025 PM 7508522 ER PT J AU WOLF, GL CROSS, AP AF WOLF, GL CROSS, AP TI REVASCULARIZATION IN PERIPHERAL VASCULAR-DISEASE - REPLY SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Letter C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02129. BRISTOL MYERS SQUIBB,DEPT BIOSTAT,WALLINGFORD,CT 06492. RP WOLF, GL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,149 13TH ST,BOSTON,MA 02129, USA. 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 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR-APR PY 1994 VL 5 IS 2 BP 392 EP 393 DI 10.1016/S1051-0443(94)71512-8 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA PB251 UT WOS:A1994PB25100025 ER PT J AU SHEPLEY, MP RACANIELLO, VR AF SHEPLEY, MP RACANIELLO, VR TI A MONOCLONAL-ANTIBODY THAT BLOCKS POLIOVIRUS ATTACHMENT RECOGNIZES THE LYMPHOCYTE HOMING RECEPTOR CD44 SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL ACTIVATION; HUMAN-ERYTHROCYTE ANTIGENS; SURFACE GLYCOPROTEINS; MOLECULAR-CLONING; HIGH ENDOTHELIUM; IN(LU) GENE; HUMAN PGP-1; HELA-CELLS; EXPRESSION; ADHESION AB A monoclonal antibody, AF3, was previously shown to specifically inhibit poliovirus binding to HeLa cells and to detect a 100-kDa glycoprotein only in cell lines and tissues permissive for poliovirus infection. These results suggested that the 100-kDa protein may be involved in the pathogenesis of poliomyelitis and the cellular function of the poliovirus receptor site. To study further the role of the 100-kDa protein in poliovirus attachment, immunoaffinity purification, amino acid sequencing, and cDNA cloning were undertaken. The results demonstrate that antibody AF3 reacts with the lymphocyte homing receptor CD44, a multifunctional cell surface glycoprotein involved in the homing of circulating lymphocytes to lymph nodes and the modulation of lymphocyte adhesion and activation. Antibody AF3 reacts with a subset of CD44 molecules ((AF3)CD44H), which appears to be a small fraction of the heterogeneously glycosylated CD44 molecules expressed on hematopoietic and nonhematopoietic cells. Anti-CD44 monoclonal antibodies, previously reported to induce CD44-mediated modulation of lymphocyte activation and adhesion, compete with I-125-AF3 in binding assays, demonstrating functional overlap among the epitopes. The anti-CD44 monoclonal antibody A3D8, which binds to a greater molecular weight range of CD44 than does AF3, inhibits poliovirus binding to a similar degree. CD44 does not act as a poliovirus receptor, since CD44-expressing mouse L-cell transformants did not bind poliovirus. The poliovirus receptor and (AF3)CD44H may be noncovalently associated, or they may interact through the cytoskeleton or signal transduction pathways. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. RP SHEPLEY, MP (reprint author), COLUMBIA UNIV,COLL PHYSICIANS & SURGEONS,DEPT MICROBIOL,701 W 168TH ST,NEW YORK,NY 10032, USA. NR 48 TC 54 Z9 56 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1301 EP 1308 PG 8 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600005 PM 7508992 ER PT J AU KALLAND, KH SZILVAY, AM LANGHOFF, E HAUKENES, G AF KALLAND, KH SZILVAY, AM LANGHOFF, E HAUKENES, G TI SUBCELLULAR-DISTRIBUTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REV AND COLOCALIZATION OF REV WITH RNA SPLICING FACTORS IN A SPECKLED PATTERN IN THE NUCLEOPLASM SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURAL GENE-EXPRESSION; VIRAL MESSENGER-RNA; TRANS-ACTIVATOR; MONOCLONAL-ANTIBODIES; RESPONSE ELEMENT; TARGET SEQUENCE; NUCLEAR RIBONUCLEOPROTEINS; FUNCTIONAL-ANALYSIS; REGULATORY GENES; AUXILIARY FACTOR AB The human immunodeficiency virus type 1 (HIV-1) Rev (regulator of virion protein expression) protein exemplifies a new type of posttranscriptional regulation. One main function of Rev is to increase the cytoplasmic expression of unspliced and incompletely spliced retroviral mRNAs from which viral structural proteins are made. In that way, Rev is essential in order to complete the retroviral life cycle. The biology of Rev in the host cell has remained elusive. In this study, a complex distribution of Rev in single cells was found. Rev was found in the cytoplasm, in a perinuclear zone, in the nucleoplasm, and in the nucleoli. In the nucleoplasm, Rev colocalized in a speckled pattern with host cell factors known to assemble on nascent transcripts. Those factors are involved in the processing of heterogeneous RNA to spliced mRNA in the nucleoplasm of all cells. The distribution of Rev was dependent only on Rev and host cell interactions, since neither the Rev target RNA nor other HIV proteins were expressed in the cells. Rev was found in the same subcellular compartments of cells treated for extended periods with cycloheximide, an inhibitor of protein synthesis. This finding implies that Rev shuttles continuously between cytoplasmic and nucleoplasmic compartments, The results suggest a potential role for Rev both in the RNA-splicing process and in the nucleocytoplasmic transport of Rev-dependent HIV mRNA. C1 UNIV BERGEN, BERGEN HIGH TECHNOL CTR, GADE INST, DEPT MICROBIOL & IMMUNOL, N-5020 BERGEN, NORWAY. DANA FARBER CANC INST, BOSTON, MA 02115 USA. RI Kalland, Karl-Henning/B-9445-2017 OI Kalland, Karl-Henning/0000-0003-4486-2334 NR 79 TC 41 Z9 41 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1475 EP 1485 PG 11 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600025 PM 8107211 ER PT J AU SHIN, CG TADDEO, B HASELTINE, WA FARNET, CM AF SHIN, CG TADDEO, B HASELTINE, WA FARNET, CM TI GENETIC-ANALYSIS OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INTEGRASE PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; DNA-BINDING; POL GENE; PRODUCTIVE INFECTION; HIV-1 INTEGRASE; RETROVIRUS DNA; INVITRO; ENDONUCLEASE; SEQUENCES; CLEAVAGE AB Single-amino-acid changes in a highly conserved central region of the human immunodeficiency virus type 1 (HIV-1) integrase protein were analyzed for their effects on viral protein synthesis, virion morphogenesis, and viral replication. Alteration of two amino acids that are invariant among retroviral integrases, D116 and E152 of HIV-1, as well as a mutation of the highly conserved amino acid S147 blocked viral replication in two CD4(+) human T-cell lines. Mutations of four other highly conserved amino acids in the region had no detectable effect on viral replication, whereas mutations at two positions, N117 and Y143, resulted in viruses with a delayed-replication phenotype. Defects in virion precursor polypeptide processing, virion morphology, or viral DNA synthesis were observed for all of the replication-defective mutants, indicating that changes in integrase can have pleiotropic effects on viral replication. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. IST SUPER SANITA,ROME,ITALY. OI Farnet, Chris/0000-0003-4927-198X FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [NCDDG U01 AI24845, P30 AI28691] NR 67 TC 102 Z9 102 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 MAR PY 1994 VL 68 IS 3 BP 1633 EP 1642 PG 10 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600043 PM 8107224 ER PT J AU HASEGAWA, K HUANG, JK ROGERS, SA BLUM, HE LIANG, TJ AF HASEGAWA, K HUANG, JK ROGERS, SA BLUM, HE LIANG, TJ TI ENHANCED REPLICATION OF A HEPATITIS-B VIRUS MUTANT ASSOCIATED WITH AN EPIDEMIC OF FULMINANT-HEPATITIS SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; ENVELOPE PROTEINS; SURFACE-ANTIGEN; SUBTYPE ADR; REVERSE TRANSCRIPTION; MONOCLONAL-ANTIBODIES; ESCHERICHIA-COLI; PRECORE REGION; GENE; RNA AB Hepatitis B virus (HBV) mutants unable to synthesize HBV e antigen have been described in association with fulminant hepatitis. We have cloned and sequenced the entire viral genome of an HBV strain associated with an epidemic of fulminant hepatitis. This strain contained, in addition to two G-to-A mutations in the precore region (nucleotides 1898 and 1901), numerous other mutations in conserved nucleotide positions resulting in significant amino acid substitutions in HBV gene products. We introduced either or both of the two G-to-A mutations into wild-type HBV by oligonucleotide-directed mutagenesis and generated replication-competent constructs of these mutants as well as the fulminant strain. Viral antigen synthesis, transcription, and replication were analyzed after transfection into human hepatoma cells. All viral constructs produced and secreted similar levels of envelope proteins (HBV surface antigen). Analysis of cellular lysate for core-specific immunoreactivity demonstrated a much higher level of core-associated antigens in cells transfected with the fulminant strain. While cells transfected with mutant and wild-type HBV DNAs synthesized similar levels of viral RNAs, the fulminant strain directed the synthesis of a much higher level of core-associated replicative intermediates (as well as virion particles) than the wild type and mutants with either or both of the precore mutations. Increase in the encapsidation of pregenomic RNA into core particles is likely the basis for the enhanced replication associated with the fulminant strain. Our study suggests that an HBV mutant with enhanced viral replication may be important in the pathogenesis of fulminant hepatic failure, and mutations other than the precore mutations may be responsible for this variant behavior. C1 MASSACHUSETTS GEN HOSP,MED SERV,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NCI NIH HHS [CA-35711, CA-54524]; NIDDK NIH HHS [DK-01952] NR 54 TC 148 Z9 152 U1 1 U2 3 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 MAR PY 1994 VL 68 IS 3 BP 1651 EP 1659 PG 9 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600045 PM 8107226 ER PT J AU DORFMAN, T MAMMANO, F HASELTINE, WA GOTTLINGER, HG AF DORFMAN, T MAMMANO, F HASELTINE, WA GOTTLINGER, HG TI ROLE OF THE MATRIX PROTEIN IN THE VIRION ASSOCIATION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTIOUS-ANEMIA VIRUS; MURINE LEUKEMIA-VIRUS; TRANSMEMBRANE GLYCOPROTEIN; INTRACELLULAR-TRANSPORT; REPLICATION-COMPETENT; CYTOPLASMIC DOMAIN; PARTICLE FORMATION; GAG POLYPROTEIN; FINE-STRUCTURE; D RETROVIRUSES AB The matrix (MA) protein of human immunodeficiency virus type 1 (HIV-1) forms an inner coat directly underneath the lipid envelope of the virion. The outer surface of the lipid envelope surrounding the capsid is coated by the viral Env glycoproteins. We report here that the HIV-1 capsid-Env glycoprotein association is very sensitive to minor alterations in the MA protein. The results indicate that most of the MA domain of the Gag precursor, except for its carboxy terminus, is essential for this association. Viral particles produced by proviruses with small missense or deletion mutations in the region coding for the amino-terminal 100 amino acids of the MA protein lacked both the surface glycoprotein gp120 and the transmembrane glycoprotein gp41, indicating a defect at the level of Env glycoprotein incorporation. Alterations at the carboxy terminus of the MA domain had no significant effect on the levels of particle-associated Env glycoprotein or on virus replication. The presence of HIV-1 MA protein sequences was sufficient for the stable association of HIV-1 Env glycoprotein with hybrid particles that contain the capsid (CA) and nucleocapsid (NC) proteins of visna virus. The association of HIV-1 Env glycoprotein with the hybrid particles was dependent upon the presence of the HIV-1 MA protein domain, as HIV-1 Env glycoprotein was not efficiently recruited into virus particles when coexpressed with authentic visna virus Gag proteins. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. OI Mammano, Fabrizio/0000-0002-9193-7696 FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691, AI29873] NR 46 TC 237 Z9 237 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 1994 VL 68 IS 3 BP 1689 EP 1696 PG 8 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600050 PM 8107229 ER PT J AU LAVALLEE, C YAO, XJ LADHA, A GOTTLINGER, H HASELTINE, WA COHEN, EA AF LAVALLEE, C YAO, XJ LADHA, A GOTTLINGER, H HASELTINE, WA COHEN, EA TI REQUIREMENT OF THE PR55(GAG) PRECURSOR FOR INCORPORATION OF THE VPR PRODUCT INTO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VIRAL PARTICLES SO JOURNAL OF VIROLOGY LA English DT Article ID VIRION-ASSOCIATED PROTEIN; OPEN READING FRAME; FUNCTIONAL-ANALYSIS; GENE-PRODUCTS; EXPRESSION; SEQUENCE; REV; HIV-1; GLYCOPROTEIN; MUTATIONS AB The human immunodeficiency virus type 1 (HIV-1) particles consists of two molecules of genomic RNA as well as molecules originating from gag, pol, and env products, all synthesized as precursor proteins. The 96-amino-acid Vpr protein, the only virion-associated HIV-1 regulatory protein, is not part of the virus polyprotein precursors, and its incorporation into virus particles must occur by way of an interaction with a component normally found in virions. To investigate the mechanism of incorporation of Vpr into the HIV-1 virion, Vpr(-) proviral DNA constructs harboring mutations or deletions in specific virion-associated gene products were cotransfected with Vpr expressor plasmids in COS cells. Virus released from the transfected cells,vas tested for the presence of Vpr by immunoprecipitation with Vpr-specific antibodies. The results of these experiments show that Vpr is trans-incorporated into virions but at a lower efficiency than when Vpr is expressed from a proviral construct. The minimal viral genetic information necessary for Vpr incorporation was a deleted provirus encoding only the pr55(gag) polyprotein precursor. Incorporation of Vpr requires the expression but not the processing of gag products and is independent of pol and env expression. Direct interaction of Vpr with the Pr55(gag) precursor protein was demonstrated by coprecipitation experiments with gag product-specific antibodies. Overall, these results indicate that HIV-1 Vpr is incorporated into the nascent virion through an interaction with the Gag precursor polyprotein and demonstrate a novel mechanism by which viral protein can be incorporated into virus particles. C1 UNIV MONTREAL,FAC MED,DEPT MICROBIOL & IMMUNOL,RETROVIROL HUMAINE LAB,MONTREAL H3C 3J7,PQ,CANADA. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. FU NIAID NIH HHS [AI 29873] NR 48 TC 115 Z9 115 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 MAR PY 1994 VL 68 IS 3 BP 1926 EP 1934 PG 9 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600076 PM 8107252 ER PT J AU MARCON, L SODROSKI, J AF MARCON, L SODROSKI, J TI GP120-INDEPENDENT FUSION MEDIATED BY THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP41 ENVELOPE GLYCOPROTEIN - A REASSESSMENT SO JOURNAL OF VIROLOGY LA English DT Note ID HUMAN MONOCLONAL-ANTIBODIES; SOLUBLE CD4 BINDING; MEMBRANE-FUSION; TRANSMEMBRANE GLYCOPROTEIN; RECEPTOR-BINDING; HTLV-III/LAV; HEMAGGLUTININ-NEURAMINIDASE; OLIGOMERIC STRUCTURE; T4 MOLECULE; ENDOPROTEOLYTIC CLEAVAGE AB In a natural context, membrane fusion mediated by the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins involves both the exterior envelope glycoprotein (gp120) and the transmembrane glycoprotein (gp41). Perez et al. (J. Virol. 66:4134-4143, 1992) reported that a mutant HIV-1 envelope glycoprotein containing only the signal peptide and carboxyl terminus of the gp120 exterior glycoprotein fused to the complete gp41 glycoprotein was properly cleaved and that the resultant gp41 glycoprotein was able to induce the fusion of even CD4-negative cells. In the studies reported herein, mutant proteins identical or similar to those studied by Perez et al. lacked detectable cell fusion activity. The proteolytic processing of these proteins was very inefficient, and one processed product identified by Perez et al. as the authentic gp41 glycoprotein was shown to contain carboxyl-terminal gp120 sequences. Furthermore, no fusion activity was observed for gp41 glycoproteins exposed after shedding of the gp120 glycoprotein by soluble CD4. Thus, evidence supporting a gpl20-independent cell fusion activity for the HIV-1 gp41 glycoprotein is currently lacking. C1 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. FU NCI NIH HHS [NCI CA09382]; NIAID NIH HHS [AI24755] NR 71 TC 14 Z9 14 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 MAR PY 1994 VL 68 IS 3 BP 1977 EP 1982 PG 6 WC Virology SC Virology GA MY596 UT WOS:A1994MY59600084 PM 8107258 ER PT J AU ANDERSON, RJ SPONSEL, HT KROLL, DJ JACKSON, S BRECKON, R HOEFFLER, JP AF ANDERSON, RJ SPONSEL, HT KROLL, DJ JACKSON, S BRECKON, R HOEFFLER, JP TI ESCAPE FROM THE ANTIPROLIFERATIVE EFFECT OF TRANSFORMING GROWTH FACTOR-BETA(1) IN LLC-PK1 RENAL EPITHELIAL-CELLS SO KIDNEY INTERNATIONAL LA English DT Article ID FACTOR-BETA; TGF-BETA; C-MYC; GENE-EXPRESSION; EXPERIMENTAL GLOMERULONEPHRITIS; INHIBITORY RESPONSES; PROXIMAL TUBULE; PROLIFERATION; SUPPRESSION; RECEPTORS AB Transforming growth factor-beta(1) (TGF-beta(1)) usually inhibits proliferation of epithelial cells. We find that LLC-PK1 renal tubular epithelial cells develop rapid in vitro resistance to the inhibitory effects of TGF-beta(1) and subsequently proliferate in response to TGF-beta(1). This unique response to TGF-beta(1) is not observed in another renal tubular epithelial cell line (MDCK cells). The proliferative response to TGF-beta(1) is additive to that produced by other growth factors. The proliferative response to TGF-beta(1) occurs despite an effect of TGF-beta(1) to suppress epidermal growth factor stimulated c-myc mRNA as determined by Northern analyses. These results suggest that LLC-PK1 cells develop rapid resistance to TGF-beta(1) inhibition of proliferation in vitro and that this resistance occurs despite continued suppression of c-myc mRNA. C1 UNIV COLORADO,HLTH SCI CTR,DIV MED ONCOL,DENVER,CO 80262. RP ANDERSON, RJ (reprint author), UNIV COLORADO,HLTH SCI CTR,DENVER VET AFFAIRS MED CTR,DEPT MED,DENVER,CO, USA. NR 42 TC 8 Z9 8 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 MAR PY 1994 VL 45 IS 3 BP 642 EP 649 DI 10.1038/ki.1994.86 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA MW173 UT WOS:A1994MW17300003 PM 8196265 ER PT J AU METSON, R WOOG, JJ PULIAFITO, CA AF METSON, R WOOG, JJ PULIAFITO, CA TI ENDOSCOPIC LASER DACRYOCYSTORHINOSTOMY SO LARYNGOSCOPE LA English DT Article ID LACRIMAL SURGERY; OBSTRUCTION AB Endoscopic laser dacryocystorhinostomy (DCR) enables an obstructed lacrimal sac to be opened through an intranasal approach, avoiding the need for a skin incision. The holmium:yttrium aluminum garnet (holmium:YAC;) laser is well-suited for this procedure because of its properties of fiberoptic delivery, effective bone cutting, and precise soft-tissue coagulation. Efficient bone ablation is particularly important for primary DCR which requires removal of relatively thick bone along the lateral nasal wall to expose the lacrimal sac. Forty-six endoscopic laser DCRs were performed on 40 patients. There were no intraoperative or postoperative complications. The surgery successfully relieved lacrimal obstruction in 85% of patients. Endoscopic instrumentation allowed for the rapid identification and correction of intranasal causes of DCR failure, including ethmoid sinus disease and middle turbinate hypertrophy. Endoscopic laser DCR appears to be a safe and effective procedure which should be considered as an alternative to external DCR for the surgical treatment of nasolacrimal duct obstruction. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. CTR EYE RES,BOSTON,MA. TUFTS UNIV,NEW ENGLAND EYE CTR,DEPT OPHTHALMOL,BOSTON,MA 02111. NR 17 TC 109 Z9 112 U1 0 U2 2 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 1994 VL 104 IS 3 BP 269 EP 274 PN 1 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA NB063 UT WOS:A1994NB06300005 PM 8127181 ER PT J AU NADOL, JB KETTEN, DR BURGESS, BJ AF NADOL, JB KETTEN, DR BURGESS, BJ TI OTOPATHOLOGY IN A CASE OF MULTICHANNEL COCHLEAR IMPLANTATION SO LARYNGOSCOPE LA English DT Article ID INSERTION TRAUMA; SPIRAL GANGLION; ELECTRICAL-STIMULATION; TEMPORAL BONES; SURVIVAL AB The histopathology of the temporal bones of a patient who died of unrelated causes 10 weeks following cochlear implantation using a Richards Ineraid(R) device is presented. Deafness was caused by a prolonged course of intravenous gentamycin therapy 5 years prior to implantation. The electrode array of the cochlear implant was left in situ throughout histologic preparation and sectioning. Despite displacement and disruption of supporting structures of the inner ear, particularly in the 6-to-15-mm range as measured from the round window, there was no significant difference in the mean densities of spiral ganglion cells in the implanted and unimplanted sides. This case is presented as evidence that despite significant disruption of supporting elements of the inner ear, which is common during cochlear implantation, there appears to be little effect on the residual spiral ganglion cell count, at least in the short term. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP NADOL, JB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [NIDCD P01 DC00361] NR 15 TC 44 Z9 45 U1 1 U2 2 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 1994 VL 104 IS 3 BP 299 EP 303 PN 1 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA NB063 UT WOS:A1994NB06300010 PM 8127186 ER PT J AU FREEDMAN, AS SAPORITO, L RHYNHART, K MORIMOTO, C NADLER, LM AF FREEDMAN, AS SAPORITO, L RHYNHART, K MORIMOTO, C NADLER, LM TI ADHESION OF FOLLICULAR LYMPHOMA-CELLS TO LYMPHOID GERMINAL-CENTERS - A POTENTIAL MECHANISM OF TUMOR-CELL HOMING FOLLOWING AUTOLOGOUS TRANSPLANTATION SO LEUKEMIA & LYMPHOMA LA English DT Article DE ADHESION; FOLLICULAR LYMPHOMA CELLS; LYMPHOID GERMINAL CENTERS; TUMOR CELL HOMING; AUTOLOGOUS BMT AB Follicular non-Hodgkin's lymphomas (NHL) generally present as disseminated diseases with infiltration of lymphoid organs, bone marrow (BM), as well as peripheral blood (PB). These lymphoma cells may recapitulate the behavior of normal germinal center (GC) B cells, some of which remain in follicles and others which have the capacity to migrate. Normal activated B cells and follicular lymphoma cells bind to GCs in vitro and this interaction is mediated by VLA-4 on the lymphoid cell and VCAM-1 on follicular dendritic cells. Since the disseminated nature of follicular NHLs may be related to the ability of PB and BM cells to recirculate through lymphoid tissues, we examined the adhesive characteristics of follicular lymphoma cells isolated from these site. Cells from 10 of 14 cases of follicular NHL involving PB or BM bound to normal GCs. Neoplastic GCs could similarly support the binding of PB or BM derived follicular NHL cells. This interaction was inhibited by monoclonal antibodies directed against VLA-4 and VCAM-1. These studies may provide insight into the clinical behavior of these diseases. More importantly the homing and adhesion of lymphoma cells is likely to be relevant to the use of PB and BM as a source of hematopoietic stem cells following high dose ablative therapy. RP FREEDMAN, AS (reprint author), DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA40216, CA55207] NR 0 TC 11 Z9 12 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 MAR PY 1994 VL 13 IS 1-2 BP 47 EP 52 DI 10.3109/10428199409051651 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA NF619 UT WOS:A1994NF61900006 PM 8025523 ER PT J AU BUNN, P ARRIAGADA, R CHOI, N FELD, R GREGOR, A JETT, J JOHNSON, B KOMAKI, R KRISTJANSEN, P MURRAY, N OHNOSHI, T PERRY, M QUOIX, E SAIJO, N SHAW, E AF BUNN, P ARRIAGADA, R CHOI, N FELD, R GREGOR, A JETT, J JOHNSON, B KOMAKI, R KRISTJANSEN, P MURRAY, N OHNOSHI, T PERRY, M QUOIX, E SAIJO, N SHAW, E TI COMBINED-MODALITY THERAPY IN SMALL-CELL LUNG-CANCER SO LUNG CANCER LA English DT Article; Proceedings Paper CT 2nd IASLC Workshop on Combined Radiotherapy and Chemotherapy Modalities in Lung Cancer CY JUN 09-13, 1992 CL FONTAINEBLEAU, FRANCE SP INT ASSOC STUDY LUNG CANC, AMGEN ROCHE, ARIES GRP FITEG, ASSOC RECH THERAPEUT CANC BRONCH, ASTA MEDICA, BRISTOL MYERS SQUIBB US, BRISTOL MYERS SQUIBB FRANCE, CIS BIO INT, FAMITALIA CARLO ERBA, INST RECH INT SERVIER, INST GUSTAVE ROUSSY, LABS SARGET, LABS LEDERLE FRANCE, LABS LILLY FRANCE, LAB PIERRE FABRE ONCOL, LABS ROGER BELLON C1 INST GUSTAVE ROUSSY,DEPT BIOSTAT,F-94805 VILLEJUIF,FRANCE. INST GUSTAVE ROUSSY,DEPT RADIOTHERAPY,F-94805 VILLEJUIF,FRANCE. MASSACHUSETTS GEN HOSP,CTR CANC,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,MED SERV,PULM UNIT,BOSTON,MA 02114. WESTERN GEN HOSP,DEPT CLIN ONCOL,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND. PRINCESS MARGARET HOSP,DEPT MED,TORONTO M4X 1K9,ONTARIO,CANADA. UNIV TORONTO,MT SINAI HOSP,DIV HAEMATOL ONCOL,TORONTO M5G 1X5,ONTARIO,CANADA. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NCCTG,OMAHA,NE. NCCTG,DES MOINES,IA. NCCTG,URBANA,IL. NCCTG,CEDAR RAPIDS,IA. NCCTG,ST CLOUD,MN. NCI,NATL NAVAL MED CTR,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIOTHERAPY,HOUSTON,TX 77030. RIGSHOSP,FINSEN INST,DEPT ONCOL,DK-2100 COPENHAGEN,DENMARK. CHR STRASBOURG,F-67005 STRASBOURG,FRANCE. NATL CANC CTR,RES INST,DIV PHARMACOL,TOKYO 104,JAPAN. OKAYAMA UNIV,SCH MED,DEPT MED,OKAYAMA 700,JAPAN. NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1994 VL 10 SU 1 BP S25 EP S28 DI 10.1016/0169-5002(94)91664-0 PG 4 WC Oncology; Respiratory System SC Oncology; Respiratory System GA NK637 UT WOS:A1994NK63700007 PM 8087517 ER PT J AU CHOI, NC KANAREK, DJ AF CHOI, NC KANAREK, DJ TI TOXICITY OF THORACIC RADIOTHERAPY ON PULMONARY-FUNCTION IN LUNG-CANCER SO LUNG CANCER LA English DT Article; Proceedings Paper CT 2nd IASLC Workshop on Combined Radiotherapy and Chemotherapy Modalities in Lung Cancer CY JUN 09-13, 1992 CL FONTAINEBLEAU, FRANCE SP INT ASSOC STUDY LUNG CANC, AMGEN ROCHE, ARIES GRP FITEG, ASSOC RECH THERAPEUT CANC BRONCH, ASTA MEDICA, BRISTOL MYERS SQUIBB US, BRISTOL MYERS SQUIBB FRANCE, CIS BIO INT, FAMITALIA CARLO ERBA, INST RECH INT SERVIER, INST GUSTAVE ROUSSY, LABS SARGET, LABS LEDERLE FRANCE, LABS LILLY FRANCE, LAB PIERRE FABRE ONCOL, LABS ROGER BELLON DE LUNG CANCER; RADIATION THERAPY; PULMONARY TOXICITY; PULMONARY FUNCTION TEST ID BRONCHOGENIC-CARCINOMA; STAGE; CHEMOTHERAPY; IRRADIATION; PNEUMONITIS; SURVIVAL; SCANS AB Physiological changes in pulmonary function (PF) as a result of radiation therapy (RT) or radiation therapy plus chemotherapy (RT + CT) for unresectable lung cancer were evaluated in an ongoing prospective study and an attempt was also made to define a guideline which can be used to minimize adverse effect of RT on pulmonary function before RT is given. The study design consisted of. (a) standard overall pulmonary function test (PFT); (b) regional PFT, i.e. a quantitative analysis of regional distribution of ventilation, perfusion and volume using N-13 and a positron camera before RT; and (c) follow-up studies of standard PFT every 6 months for 3 years after RT or RT + CT. Predicted post-RT PF prior to RT was calculated by a formula: predicted FEV1 after RT = FEV1 before RT X (1 - an average of the percent of ventilation and perfusion contributed by lung tissue within the RT treatment volume). A total of 267 patients with unresectable, but still potentially curable lung cancer by RT were entered into this study, and 135 patients who were free of recurrence underwent repeat studies. Loss of PF as a result of RT is closely related to the degree of PF reserve prior to RT. Patients with FEV1 > 50% of the predicted showed a statistically significant decrease in FEV1, FVC, MBC, peak expiratory flow rate and DLCO, i.e. a 22% loss of the initial value. Airway resistance was increased by 31%. Two-thirds of this group of patients showed a decrease in PF as predicted by the above formula. For patients with limited PF reserve defined by FEV1 < 50% of the predicted, the pattern of PF loss after RT was quite different. An improvement in PF although it was less-than-or-equal-to 10%, contrary to the prediction, was noted in 50% of patients, and another 37% of patients showed a small decrease in PF (less-than-or-equal-to 10% of the initial value). Only 13% of patients showed a loss of pulmonary function as predicted by regional PF data. Patients with a significant shift (> 10%) of ventilation and/or perfusion to the uninvolved side of the lung by centrally located primary tumor or involved lymph nodes showed an increase in PF in 60% of patients after RT, and another 20% of patients showed a minor decrease in PF (< 10% of the initial value). Only 20% of these patients showed a decrease in pulmonary function as predicted by regional PF data. Guidelines for minimizing adverse effect of RT on PF, which are based on the initial PF reserve and regional PF data, are presented. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MED SERV,PULM UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP CHOI, NC (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 33 TC 42 Z9 43 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1994 VL 10 SU 1 BP S219 EP S230 DI 10.1016/0169-5002(94)91685-3 PG 12 WC Oncology; Respiratory System SC Oncology; Respiratory System GA NK637 UT WOS:A1994NK63700028 PM 8087514 ER PT J AU COX, J BALL, D BELANI, C CHOI, N GRALLA, R HALLE, J KOMAKI, R LECHEVALIER, T OHNOSHI, T QUOIX, E RUFFIE, P SHAW, E SOUHAMI, R TURRISI, A AF COX, J BALL, D BELANI, C CHOI, N GRALLA, R HALLE, J KOMAKI, R LECHEVALIER, T OHNOSHI, T QUOIX, E RUFFIE, P SHAW, E SOUHAMI, R TURRISI, A TI DOSE INTENSITY IN LUNG-CANCER TREATMENT SO LUNG CANCER LA English DT Article; Proceedings Paper CT 2nd IASLC Workshop on Combined Radiotherapy and Chemotherapy Modalities in Lung Cancer CY JUN 09-13, 1992 CL FONTAINEBLEAU, FRANCE SP INT ASSOC STUDY LUNG CANC, AMGEN ROCHE, ARIES GRP FITEG, ASSOC RECH THERAPEUT CANC BRONCH, ASTA MEDICA, BRISTOL MYERS SQUIBB US, BRISTOL MYERS SQUIBB FRANCE, CIS BIO INT, FAMITALIA CARLO ERBA, INST RECH INT SERVIER, INST GUSTAVE ROUSSY, LABS SARGET, LABS LEDERLE FRANCE, LABS LILLY FRANCE, LAB PIERRE FABRE ONCOL, LABS ROGER BELLON C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIOTHERAPY,HOUSTON,TX 77030. PETER MACCALLUM CANC INST,MELBOURNE,VIC 3000,AUSTRALIA. UNIV MARYLAND,CTR CANC,BALTIMORE,MD 21201. UNIV MICHIGAN,MED CTR,DEPT RADIAT ONCOL,ANN ARBOR,MI 48109. UNIV COLL & MIDDLESEX SCH MED,DEPT ONCOL,LONDON W1P 8BT,ENGLAND. MASSACHUSETTS GEN HOSP,CTR CANC,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,MED SERV,PULM UNIT,BOSTON,MA 02114. INST GUSTAVE ROUSSY,DEPT BIOSTAT,F-94805 VILLEJUIF,FRANCE. INST GUSTAVE ROUSSY,DEPT RADIOTHERAPY,F-94805 VILLEJUIF,FRANCE. CTR HOSP INTERCOMMUNAL CRETEIL,F-94010 CRETEIL,FRANCE. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NCCTG,DES MOINES,IA. NCCTG,OMAHA,NE. NCCTG,ST CLOUD,NE. NCCTG,CEDAR RAPIDS,IA. NCCTG,URBANA,IL. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1994 VL 10 SU 1 BP S11 EP S13 DI 10.1016/0169-5002(94)91661-6 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA NK637 UT WOS:A1994NK63700004 PM 8087500 ER PT J AU GREEN, M BRODIN, O CHOI, N DRINGS, P GINSBERG, R GRALLA, R JOHNSON, D MULSHINE, J PAYNE, D RUFFIE, P AF GREEN, M BRODIN, O CHOI, N DRINGS, P GINSBERG, R GRALLA, R JOHNSON, D MULSHINE, J PAYNE, D RUFFIE, P TI PREOPERATIVE AND POSTOPERATIVE TREATMENTS IN STAGE-III NSCLC SO LUNG CANCER LA English DT Article; Proceedings Paper CT 2nd IASLC Workshop on Combined Radiotherapy and Chemotherapy Modalities in Lung Cancer CY JUN 09-13, 1992 CL FONTAINEBLEAU, FRANCE SP INT ASSOC STUDY LUNG CANC, AMGEN ROCHE, ARIES GRP FITEG, ASSOC RECH THERAPEUT CANC BRONCH, ASTA MEDICA, BRISTOL MYERS SQUIBB US, BRISTOL MYERS SQUIBB FRANCE, CIS BIO INT, FAMITALIA CARLO ERBA, INST RECH INT SERVIER, INST GUSTAVE ROUSSY, LABS SARGET, LABS LEDERLE FRANCE, LABS LILLY FRANCE, LAB PIERRE FABRE ONCOL, LABS ROGER BELLON C1 UNIV HOSP UPPSALA,DEPT ONCOL,UPPSALA,SWEDEN. MASSACHUSETTS GEN HOSP,CTR CANC,DEPT RADIAT ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,MED SERV,PULM UNIT,BOSTON,MA 02114. CORNELL UNIV,MED CTR,COLL MED,DEPT SURG,THORAC SERV,NEW YORK,NY 10021. THORAXKLIN HEIDELBERG ROHRBACH,DEPT ONCOL,W-6900 HEIDELBERG,GERMANY. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,DIV MED ONCOL,NASHVILLE,TN 37232. PRINCESS MARGARET HOSP,DEPT RADIAT ONCOL,TORONTO M4X 1K9,ONTARIO,CANADA. UNIV TORONTO,TORONTO M4X 1K9,ONTARIO,CANADA. INST GUSTAVE ROUSSY,F-94805 VILLEJUIF,FRANCE. CTR HOSP INTERCOMMUNAL CRETEIL,F-94010 CRETEIL,FRANCE. NCI,DIV CANC & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. NCI,DIV CANC & CONTROL,EARLY DETECT & COMMUNITY ONCOL PROGRAM,ROCKVILLE,MD 20850. RP GREEN, M (reprint author), UNIV CALIF SAN DIEGO,225 DICKINSON ST,8421,SAN DIEGO,CA 92103, USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1994 VL 10 SU 1 BP S15 EP S17 DI 10.1016/0169-5002(94)91662-4 PG 3 WC Oncology; Respiratory System SC Oncology; Respiratory System GA NK637 UT WOS:A1994NK63700005 PM 8087504 ER PT J AU GARRIDO, L PFLEIDERER, B JENKINS, BG HULKA, CA KOPANS, DB AF GARRIDO, L PFLEIDERER, B JENKINS, BG HULKA, CA KOPANS, DB TI MIGRATION AND CHEMICAL MODIFICATION OF SILICONE IN WOMEN WITH BREAST PROSTHESES SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE SILICONE; MIGRATION; CHEMICAL MODIFICATION; H-1 AND SI-29 NMR ID SI-29 NMR AB Studies using magnetic resonance spectroscopy in human volunteers to evaluate their livers in vivo and to analyze their blood in vitro suggest that there are measurable amounts of silicon compounds in the blood of some women with implants and that there is migration of silicone to other organs such as the liver. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,CTR BREAST IMAGING,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. RP GARRIDO, L (reprint author), MASSACHUSETTES GEN HOSP,CTR NMR,149 13TH ST,BOSTON,MA 02129, USA. RI Garrido, Leoncio/K-3092-2014 OI Garrido, Leoncio/0000-0002-7587-1260 NR 7 TC 52 Z9 52 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD MAR PY 1994 VL 31 IS 3 BP 328 EP 330 DI 10.1002/mrm.1910310314 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MY332 UT WOS:A1994MY33200013 PM 8057806 ER PT J AU PICARD, MH WEYMAN, AE AF PICARD, MH WEYMAN, AE TI ECHOCARDIOGRAPHIC ASSESSMENT OF LEFT-VENTRICULAR MASS - WHAT MORE CAN WE LEARN SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID HYPERTENSIVE PATIENTS; HYPERTROPHY; IMPACT; YOUNG; SIZE; AGE RP PICARD, MH (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114, USA. OI Picard, Michael/0000-0002-9264-3243 NR 18 TC 1 Z9 1 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAR PY 1994 VL 69 IS 3 BP 291 EP 292 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MZ902 UT WOS:A1994MZ90200016 PM 8133670 ER PT J AU SCHIFF, I UTIAN, WH AF SCHIFF, I UTIAN, WH TI A NEW SCHOLARLY JOURNAL ON MENOPAUSE SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DIV WOMENS CARE,VINCENT MEM OBSTET & GYNECOL SERV,BOSTON,MA 02114. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH 44106. UNIV CLEVELAND HOSP,DEPT OBSTET & GYNECOL,CLEVELAND,OH 44106. RP SCHIFF, I (reprint author), HARVARD UNIV,SCH MED,32 FRUIT ST,BOSTON,MA 02114, USA. 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 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SPR PY 1994 VL 1 IS 1 BP 1 EP 1 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QB024 UT WOS:A1994QB02400001 ER PT J AU UTIAN, WH SCHIFF, I AF UTIAN, WH SCHIFF, I TI NAMS-GALLUP SURVEY ON WOMENS KNOWLEDGE, INFORMATION-SOURCES, AND ATTITUDES TO MENOPAUSE AND HORMONE REPLACEMENT THERAPY SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE HORMONE REPLACEMENT THERAPY; HYSTERECTOMY; NAMS; GALLUP SURVEY ID ESTROGEN AB The North American Menopause Society (NAMS) sponsored a Gallup Organization survey of 833 women aged 45-60 to determine attitudes and experience with menopause and various forms of hormone replacement therapy (HRT). The results of this survey are presented herein. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT OBSTET & GYNECOL,CLEVELAND,OH 44106. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEP GYNECOL,DIV WOMENS CARE,VINCENT MEM GYNECOL SERV,BOSTON,MA 02114. NR 7 TC 115 Z9 118 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SPR PY 1994 VL 1 IS 1 BP 39 EP 48 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QB024 UT WOS:A1994QB02400007 ER PT J AU GOODMAN, L AWWAD, J MARC, K SCHIFF, I AF GOODMAN, L AWWAD, J MARC, K SCHIFF, I TI CONTINUOUS COMBINED HORMONAL REPLACEMENT THERAPY AND THE RISK OF ENDOMETRIAL CANCER - PRELIMINARY-REPORT SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE HORMONE REPLACEMENT THERAPY; ENDOMETRIAL CANCER; ESTROGEN ID MEDROXYPROGESTERONE ACETATE; POSTMENOPAUSAL WOMEN; PROGESTOGEN THERAPY; ESTROGEN AB We present the case histories of two women diagnosed with endometrial adenocarcinoma during continuous combined hormonal replacement therapy (HRT). Although these findings do not necessarily favor a causal association, they remain of concern. In the absence of a well-designed study evaluating the long-term safety of continuous combined HRT, closer monitoring of the endometrium with baseline and routine periodic histologic evaluation may be necessary. The occurrence of uterine bleeding in women receiving this made of HRT warrants a thorough investigation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV WOMENS CARE,VINCENT MEM GYNECOL SERV,BOSTON,MA 02114. HARVARD UNIV,NEWTON WELLESLEY HOSP,DEPT GYNECOL,BOSTON,MA 02114. NR 20 TC 10 Z9 10 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SPR PY 1994 VL 1 IS 1 BP 57 EP 59 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QB024 UT WOS:A1994QB02400009 ER PT J AU TOMERA, JF LILFORD, K KUKULKA, SP FRIEND, KD HARAKAL, C AF TOMERA, JF LILFORD, K KUKULKA, SP FRIEND, KD HARAKAL, C TI DIVALENT-CATIONS IN HYPERTENSION WITH IMPLICATIONS TO HEART-DISEASE - CALCIUM, CADMIUM INTERACTIONS SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article DE CADMIUM; CALCIUM; CADMIUM-INDUCED HYPERTENSION; MEAN BLOOD PRESSURE; RENAL HYPERTENSION ID PLASMA-MEMBRANE AB Heart disease still pervades a socioeconomic classes within the United States. Understanding the effects of environmentally-related pathogenesis (e.g., heavy metal accumulation) may aid in developing novel treatments for the prevention of heart dysfunction. The aim of this report was to use experimental investigation in an attempt to expand upon the multivariate importance of divalent cation interactions in the development of heart disease. Calcium and cadmium levels were measured by flame atomic absorption spectrophotometry in various tissues derived from two types of hypertensive rabbit models. Both models of hypertension developed mean arterial pressures of at least 50 mm mercury greater than those of controls over a 5 week period. Interrelationships between calcium and cadmium levels were found to exist for both hypertensive groups in the left ventricle, aorta, and renal medulla. The renal cortex showed no such interrelationship for the renal hypertensive group. Multiple interrelationships between calcium and cadmium levels and hypertrophy were also observed. These studies related the importance of endogenous or exogenous (viz, environmental) factors governing cadmium and calcium accumulation in hypertensive rabbits. The resulting relationships between divalent cations and hypertrophy were presented to draw attention to areas which remain unexplored with perspective to cardiovascular disease. C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,ANESTHESIA SERV,CLIN PHARMACOL LAB,BOSTON,MA 02114. TEMPLE UNIV,HLTH SCI CTR,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19140. RP TOMERA, JF (reprint author), SHRINERS BURNS RES CTR,ANESTHESIA SERV,1 KENDALL SQ,CLIN PHARMACOL LAB,BLDG 1400W,CAMBRIDGE,MA 02142, USA. FU NHLBI NIH HHS [HL 14217] NR 20 TC 12 Z9 12 U1 0 U2 1 PU J R PROUS SA PI BARCELONA PA APARTADO DE CORREOS 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD MAR PY 1994 VL 16 IS 2 BP 97 EP 107 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ND830 UT WOS:A1994ND83000004 PM 8007748 ER PT J AU BAES, M GULICK, T CHOI, HS MARTINOLI, MG SIMHA, D MOORE, DD AF BAES, M GULICK, T CHOI, HS MARTINOLI, MG SIMHA, D MOORE, DD TI A NEW ORPHAN MEMBER OF THE NUCLEAR HORMONE-RECEPTOR SUPERFAMILY THAT INTERACTS WITH A SUBSET OF RETINOIC ACID RESPONSE ELEMENTS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DEPENDENT TRANSCRIPTIONAL ACTIVATION; THYROID-HORMONE; GROWTH-HORMONE; DNA-BINDING; X-RECEPTOR; RXR-BETA; DEHYDROGENASE GENE; PROMOTER ELEMENTS; TARGET SEQUENCES; ONCOGENE PRODUCT AB We have identified and characterized a new orphan member of the nuclear hormone receptor superfamily, called MB67, which is predominantly expressed in liver. MB67 binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes, both of which consist of a direct repeat hexamers related to the consensus AGGTCA, separated by 5 bp. MB67 binds these elements as a heterodimer with the 9-cis-retinoic acid receptor, RXR. However, MB67 does not bind or activate other retinoic acid response elements with alternative hexamer arrangements or any of several other wild-type and synthetic hormone response elements examined. The transactivation of retinoic acid response elements by MB67 is weaker than that conferred by the retinoic acid receptors but does not require the presence of all-trans retinoic acid, 9-cis-retinoic acid, or any exogenously added ligand, We propose that MB67 plays an important role in the complex network of proteins that govern response to retinoic acid and its metabolites. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. FU NIDDK NIH HHS [R01DK43382] NR 75 TC 352 Z9 362 U1 1 U2 3 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 MAR PY 1994 VL 14 IS 3 BP 1544 EP 1552 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MX640 UT WOS:A1994MX64000002 PM 8114692 ER PT J AU JAIN, JN NALEFSKI, EA MCCAFFREY, PG JOHNSON, RS SPIEGELMAN, BM PAPAIOANNOU, V RAO, A AF JAIN, JN NALEFSKI, EA MCCAFFREY, PG JOHNSON, RS SPIEGELMAN, BM PAPAIOANNOU, V RAO, A TI NORMAL PERIPHERAL T-CELL FUNCTION IN C-FOS-DEFICIENT MICE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION; EXPRESSION; ACTIVATION; GENE; JUN; TRANSCRIPTION; RECEPTOR; PROTEIN; FIBROBLASTS AB The ubiquitous transcription factors Fos and Jun are rapidly induced in T cells stimulated through the T-cell antigen receptor and regulate transcription of cytokines, including interleukin 2, in activated T cells. Since positive and negative selection of thymocytes during T-cell development also depends on activation through the T-cell receptor, Fos and Jun may play a role in thymocyte development as well. Fos and Jun act at several regulatory elements in the interleukin 2 promoter, including the AP-1 and NFAT sites. Using antisera specific to individual Fos and Jun family members, we show that c-Fos as well as other Fos family members are present in the inducible AP-1 and NFAT complexes of activated murine T cells. Nevertheless, c-Fos is not absolutely required for the development or function of peripheral T cells, as shown by using mice in which both copies of the c-fos gene were disrupted by targeted mutagenesis. c-Fos-deficient mice were comparable to wild-type mice in their patterns of thymocyte development and in the ability of their peripheral T cells to proliferate and produce several cytokines in response to T-cell receptor stimulation. Our results suggest that other Fos family members may be capable of substituting functionally for c-Fos during T-cell development and cytokine gene transcription in activated T cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. OI Johnson, Randall/0000-0002-4084-6639 FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI22900]; NICHD NIH HHS [HD27295] NR 51 TC 60 Z9 60 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 MAR PY 1994 VL 14 IS 3 BP 1566 EP 1574 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MX640 UT WOS:A1994MX64000004 PM 8114694 ER PT J AU BUNKER, CA KINGSTON, RE AF BUNKER, CA KINGSTON, RE TI TRANSCRIPTIONAL REPRESSION BY DROSOPHILA AND MAMMALIAN POLYCOMB GROUP PROTEINS IN TRANSFECTED MAMMALIAN-CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POSITION-EFFECT VARIEGATION; HUMAN HSP70 PROMOTER; POSTERIOR SEX COMBS; MYC TRANSGENIC MICE; BITHORAX COMPLEX; GROUP GENES; MELANOGASTER; EXPRESSION; CHROMATIN; YEAST AB The Polycomb group (Pc-G) genes are essential for maintaining the proper spatially restricted expression pattern of the homeotic loci during Drosophila development. The Pc-G proteins appear to function at target loci to maintain a state of transcriptional repression. The murine oncogene bmi-1 has significant homology to the Pc-G gene Posterior sex combs (Psc) and a highly related gene, Suppressor two of zeste [Sn(z)2]. We show here that the proteins encoded by bmi-l and the Pc-G genes Polycomb (Pc) and Psc as well as Su(z)2 mediate repression in mammalian cells when targeted to a promoter by LexA in a cotransfection system. These fusion proteins repress activator function by as much as 30-fold, and the effect on different activation domains is distinct for each Pc-G protein. Repression is observed when the LexA fusion proteins are bound directly adjacent to activator binding sites and also when bound 1,700 bases from the promoter. These data demonstrate that the products of the Pc-G genes can significantly repress activator function on transiently introduced DNA. We suggest that this function contributes to the stable repression of targeted loci during development. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. FU NIGMS NIH HHS [GM48405] NR 52 TC 116 Z9 117 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 MAR PY 1994 VL 14 IS 3 BP 1721 EP 1732 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MX640 UT WOS:A1994MX64000019 PM 7906858 ER PT J AU LORENZ, U RAVICHANDRAN, KS PEI, D WALSH, CT BURAKOFF, SJ NEEL, BG AF LORENZ, U RAVICHANDRAN, KS PEI, D WALSH, CT BURAKOFF, SJ NEEL, BG TI LCK-DEPENDENT TYROSYL PHOSPHORYLATION OF THE PHOSPHOTYROSINE PHOSPHATASE SH-PTP1 IN MURINE T-CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; SH3 DOMAINS; PROTEIN; EXPRESSION; ACTIVATION; SEQUENCE; HOMOLOGY; FAMILY; IDENTIFICATION AB The phosphorylation and dephosphorylation of proteins on tyrosyl residues are key regulatory mechanisms in T-cell signal transduction and are controlled by the opposing activities of protein tyrosine kinases and phosphotyrosyl phosphatases (PTPs). In T cells, several nontransmembrane protein tyrosine kinases are associated with receptors; for example, Lck is bound to the coreceptors CD4 and CD8 and becomes activated upon their stimulation. In comparison, little is known about the role of nontransmembrane PTPs in early T-cell signaling. SH-PTP1 (PTP1C, HCP, SHP) is a nontransmembrane PTP expressed primarily in hematopoietic cells, including T cells. We have found that SH-PTP1 is basally phosphorylated on serine in resting T cells. Upon stimulation of CD4 or CD8 either in a T-cell hybridoma cell line or in primary thymocytes, SH-PTP1 becomes tyrosyl phosphorylated. Moreover, SH-PTP1 is constitutively phosphorylated on tyrosine in the Lck-overexpressing lymphoma cell line LSTRA. SH-PTP1 is also a good substrate for recombinant Lck in vitro. Comparisons of the tryptic phosphopeptide maps of mild-type SH-PTP1 and deletion and point mutations establish that the two sites (Y-536 and Y-564) which are directly phosphorylated by Lck in vitro are also phosphorylated in vivo in LSTRA cells. One of these sites (Y-564) is phosphorylated in T cells in response to Lck activation. We conclude that SH-PTP1 undergoes Lck-dependent tyrosyl phosphorylation in T cells and likely plays a role in early T-cell signaling. C1 DANA FARBER CANC INST, DIV PEDIAT ONCOL, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. RP BETH ISRAEL HOSP, MOLEC MED UNIT, 330 BROOKLINE AVE, BOSTON, MA 02215 USA. FU NCI NIH HHS [CA49152]; NIAID NIH HHS [AI-17258]; NIGMS NIH HHS [GM20011] NR 59 TC 140 Z9 140 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1994 VL 14 IS 3 BP 1824 EP 1834 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MX640 UT WOS:A1994MX64000029 PM 8114715 ER PT J AU LI, Y SLANSKY, JE MYERS, DJ DRINKWATER, NR KAELIN, WG FARNHAM, PJ AF LI, Y SLANSKY, JE MYERS, DJ DRINKWATER, NR KAELIN, WG FARNHAM, PJ TI CLONING, CHROMOSOMAL LOCATION, AND CHARACTERIZATION OF MOUSE E2F1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR E2F; REDUCTASE GENE PROMOTER; RNA POLYMERASE-II; DNA-BINDING; CYCLIN-A; STIMULATED CELLS; PROTEIN; INITIATION; EXPRESSION; SEQUENCES AB E2F has been implicated in growth control because of its association with the retinoblastoma protein and the presence of E2F binding sites in the promoters of several growth-regulated genes. Proteins that bind to an E2F site have been cloned from human and mouse cells. However, these two proteins (human E2F1 and mouse DP-I) are quite different in sequence. We have now cloned a mouse cDNA encoding a protein 86% identical to the human E2F1 protein. The mouse E2F1 cDNA encodes a 430-amino-acid protein with a predicted molecular weight of 46,322 and detects mRNAs of 2.7 and 2.2 kb. Using primers complementary to sequences in the mouse E2F1 3' untranslated region, we mapped the mouse E2F1 gene to chromosome 2, near the Agouti and c-src loci. To understand the role of the different E2F family members in the growth of mouse NIH 3T3 cells, we examined the levels of E2F1 and DP-I mRNAs in different stages of the cell cycle. Since the levels of E2F1 but not DP-I mRNA correlated with changes in transcription from the dhfr promoter, we examined whether E2F1 could activate various growth-regulated promoters. We found that E2F1 could activate some (dhfr, thymidine kinase, and DNA polymerase alpha) but not all (thymidylate synthase, cad, and c-myc) of these promoters. On the basis of changes in levels of E2F1 and its ability to transactivate growth-regulated promoters, we propose that E2F1 may mediate growth factor-initiated signal transduction. C1 UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA07175, CA45240, CA23076] NR 46 TC 90 Z9 91 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 MAR PY 1994 VL 14 IS 3 BP 1861 EP 1869 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MX640 UT WOS:A1994MX64000033 PM 8114719 ER PT J AU MEYERSON, M HARLOW, E AF MEYERSON, M HARLOW, E TI IDENTIFICATION OF G(1) KINASE-ACTIVITY FOR CDK6, A NOVEL CYCLIN-D PARTNER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETINOBLASTOMA-SUSCEPTIBILITY GENE; CDC2-RELATED PROTEIN-KINASE; CELL-CYCLE; CDC2 KINASE; TRANSCRIPTION FACTOR; RB PROTEIN; 2 MEMBERS; S-PHASE; PRODUCT; PHOSPHORYLATION AB A family of vertebrate cdc2-related kinases has been identified, and these kinases are candidates for roles in cell cycle regulation. Here, we show that the human PLSTIRE gene product is a novel cyclin-dependent kinase, cdk6. The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. Furthermore, we demonstrate that endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene. The activation of cdk6 kinase occurs during mid-G, in phytohemagglutinin-stimulated T cells, well prior to the activation of cdk2 kinase. This timing suggests that cdk6, and by analogy its homolog cdk4, links growth factor stimulation with the onset of cell cycle progression. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RP MEYERSON, M (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 149,13TH ST,BOSTON,MA 02129, USA. RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [T32-CA09216] NR 74 TC 692 Z9 702 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 MAR PY 1994 VL 14 IS 3 BP 2077 EP 2086 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MX640 UT WOS:A1994MX64000057 PM 8114739 ER PT J AU TSUKUROV, O BOEHMER, A FLYNN, J NICOLAI, JP HAMEL, BCJ TRAILL, S ZALESKE, D MANKIN, HJ YEON, H HO, C TABIN, C SEIDMAN, JG SEIDMAN, C AF TSUKUROV, O BOEHMER, A FLYNN, J NICOLAI, JP HAMEL, BCJ TRAILL, S ZALESKE, D MANKIN, HJ YEON, H HO, C TABIN, C SEIDMAN, JG SEIDMAN, C TI A COMPLEX BILATERAL POLYSYNDACTYLY DISEASE LOCUS MAPS TO CHROMOSOME 7Q36 SO NATURE GENETICS LA English DT Article ID GENE; FAMILIES; LINKAGE; EN-2 AB We demonstrate that the gene responsible for a congenital limb deformity (polysyndactyly) maps to chromosome 7q36 in a large family. Pre- and postaxial anomalies of the extremities are inherited in this family as an autosomal dominant trait. The disease locus is closely linked to D7S550 (maximum lod score = 6.85, theta = 0). This region is homologous to a segment of mouse chromosome 5, where the mutations hammer toe (HM) and hemimelic extra toes (HX) have been mapped. These data suggest that human chromosome 7q36 and the homologous region of mouse chromosome 5 contain genes involved in limb pattern formation. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PEDIAT ORTHOPED UNIT,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED,BOSTON,MA 02114. ERASMUS UNIV ROTTERDAM,DEPT ENDOCRINOL & REPROD,3000 DR ROTTERDAM,NETHERLANDS. CHILDRENS HOSP,DEPT PEDIAT,ROTTERDAM,NETHERLANDS. REG CTR PLAST RECONSTRUCT & HAND SURG,ARNHEM,NETHERLANDS. UNIV HOSP NIJMEGEN,DEPT HUMAN GENET,6500 HB NIJMEGEN,NETHERLANDS. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. NR 28 TC 76 Z9 83 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 MAR PY 1994 VL 6 IS 3 BP 282 EP 286 DI 10.1038/ng0394-282 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA MZ562 UT WOS:A1994MZ56200016 PM 8012391 ER PT J AU VELINOV, M SLAUGENHAUPT, SA STOILOV, I SCOTT, CI GUSELLA, JF TSIPOURAS, P AF VELINOV, M SLAUGENHAUPT, SA STOILOV, I SCOTT, CI GUSELLA, JF TSIPOURAS, P TI THE GENE FOR ACHONDROPLASIA MAPS TO THE TELOMERIC REGION OF CHROMOSOME 4P SO NATURE GENETICS LA English DT Article ID L-IDURONIDASE GENE; HOMOZYGOUS ACHONDROPLASIA; CANDIDATE REGION; II COLLAGEN; LOCUS; IDENTIFICATION; LOCALIZATION; POLYMORPHISM; CARTILAGE; MARKERS AB Achondroplasia is the most common type of genetic dwarfism. It is characterized by disproportionate short stature and other skeletal anomalies resulting from a defect in the maturation of the chondrocytes in the growth plate of the cartilage. We have now mapped the achondroplasia gene near the telomere of the short arm of chromosome 4 (4p16.3), by family linkage studies using 14 pedigrees. A positive lod score of z=3.35 with no recombinants was obtained with an intragenic marker for IDUA. This localization wilt facilitate the positional cloning of the disease gene. C1 UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT,FARMINGTON,CT 06030. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. ALFRED I DUPONT INST,DIV MED GENET,WILMINGTON,DE 19899. NR 41 TC 80 Z9 81 U1 0 U2 4 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 MAR PY 1994 VL 6 IS 3 BP 314 EP 317 DI 10.1038/ng0394-314 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA MZ562 UT WOS:A1994MZ56200022 PM 8012397 ER PT J AU BEAL, MF AF BEAL, MF TI HUNTINGTONS-DISEASE, ENERGY, AND EXCITOTOXICITY SO NEUROBIOLOGY OF AGING LA English DT Article ID QUINOLINIC ACID; LESIONS; RECEPTOR; IMPAIRMENT; METABOLISM; GLUTAMATE C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP BEAL, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. NR 13 TC 50 Z9 50 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAR-APR PY 1994 VL 15 IS 2 BP 275 EP 276 PG 2 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA NA567 UT WOS:A1994NA56700028 PM 7838311 ER PT J AU ROFFLERTARLOV, S CHENG, S LIN, CS WENSLEY, CH GRAYBIEL, AM GUSELLA, JF AF ROFFLERTARLOV, S CHENG, S LIN, CS WENSLEY, CH GRAYBIEL, AM GUSELLA, JF TI THE CHROMOSOMAL LOCATION OF THE MURINE MUTATION WEAVER SO NEURODEGENERATION LA English DT Article DE MUTATION; WEAVER GENE; CEREBELLUM; SUBSTANTIA NIGRA; INTERSPECIFIC CROSS ID DOPAMINE-CONTAINING INNERVATION; MOUSE CHROMOSOME-16; MUTANT MICE; NEUROLOGICAL MUTANT; PARKINSONS-DISEASE; CEREBELLAR CORTEX; SUBSTANTIA NIGRA; GENE-ACTION; CELL LOSS; RECOMBINATION C1 ARES ADV TECHNOL,RANDOLPH,MA 02368. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. RP ROFFLERTARLOV, S (reprint author), TUFTS UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02111, USA. NR 51 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1055-8330 J9 NEURODEGENERATION JI Neurodegeneration PD MAR PY 1994 VL 3 IS 1 BP 61 EP 72 PG 12 WC Neurosciences SC Neurosciences & Neurology GA NG942 UT WOS:A1994NG94200007 ER PT J AU KEANE, MM GABRIELI, JDE GROWDON, JH CORKIN, S AF KEANE, MM GABRIELI, JDE GROWDON, JH CORKIN, S TI PRIMING IN PERCEPTUAL IDENTIFICATION OF PSEUDOWORDS IS NORMAL IN ALZHEIMERS-DISEASE SO NEUROPSYCHOLOGIA LA English DT Article ID ALCOHOLIC KORSAKOFF PATIENTS; WORD-STEM-COMPLETION; IMPLICIT MEMORY; EXPLICIT MEMORY; STRUCTURAL DESCRIPTIONS; PARKINSONS-DISEASE; AMNESIC PATIENTS; READING ALOUD; ACTIVATION; ASSOCIATIONS AB Patients with Alzheimer's disease (AD) have deficits in recall and recognition memory, and show dissociable performance in repetition priming tasks: They exhibit impaired priming in word-completion and word-generation tasks, but normal priming in perceptual identification of words. In order to examine whether AD patients can show normal priming with novel, unfamiliar stimuli, the present study examined their performance in perceptual identification of pseudowords. Despite impaired recognition memory performance, AD patients showed normal priming in perceptual identification of pseudowords. These results extend the boundaries of intact repetition priming in AD, demonstrating that such priming is not limited to stimuli that are pre-morbidly represented in long-term knowledge. Preserved repetition priming in AD may reflect the operation of perceptual processes localized to posterior visual circuits that are relatively spared in AD. C1 MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. BOSTON UNIV,SCH MED,MEMORY DISORDERS RES CTR,BOSTON,MA 02118. MIT,CLIN RES CTR,CAMBRIDGE,MA 02139. DEPT VET AFFAIRS MED CTR,BOSTON,MA. STANFORD UNIV,DEPT PSYCHOL,STANFORD,CA 94305. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NIA NIH HHS [AG06605, 1P50AG05134]; NINDS NIH HHS [NS26985] NR 66 TC 67 Z9 67 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD MAR PY 1994 VL 32 IS 3 BP 343 EP 356 DI 10.1016/0028-3932(94)90136-8 PG 14 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA NC096 UT WOS:A1994NC09600006 PM 8202228 ER PT J AU EDWARDS, MA CRANDALL, JE LECLERC, N YAMAMOTO, M AF EDWARDS, MA CRANDALL, JE LECLERC, N YAMAMOTO, M TI EFFECTS OF NERVOUS MUTATION ON PURKINJE-CELL COMPARTMENTS DEFINED BY ZEBRIN-II AND 9-O-ACETYLATED GANGLIOSIDES EXPRESSION SO NEUROSCIENCE RESEARCH LA English DT Article DE CEREBELLUM; NERVOUS MUTANT MICE; PURKINJE CELLS; COMPARTMENTATION; ZEBRIN-II; 9-O-ACETYLATED GANGLIOSIDES ID RAT CEREBELLAR CORTEX; MUTANT MOUSE; PARASAGITTAL ORGANIZATION; BANDS; ANTIBODIES; MABQ113; PROJECTION; NEURONS; NUCLEUS; MICE AB The cerebellum is organized into a series of parasagittally aligned bands which are well delineated in the adult mouse by the largely complementary immunostaining of Purkinje cell groups with the monoclonal antibodies Zebrin II (ZII; antigen: aldolase C) and P-path (antigen: 9-O-acetyl gangliosides). We examined the effect of nervous mutation on compartmental organization using these markers and an antibody to calbindin. In nervous mutant, up to 90% of Purkinje cells die in late postnatal development. The size of the cerebellum is about half that of normal, and caudal lobules appear to decrease in size more than anterior ones. Surviving Purkinje cells corresponded to P-path positive ones that were concentrated in two bilateral bands in the vermis and in medial portions of the hemispheres. Only small numbers of ZII positive cells remained, confirming the report by Wassef et al. with Zebrin I antibody. They were primarily located in caudal lobules IX, X and a portion of lobule IV, paraflocculus and flocculus, and their immunoreactivity was weak compared to that of normal. ZII positive cells are dominant in these caudal lobules, while P-path positive cells dominate in rostral lobules in normal mice, and the similar tendency remains in mutant. Thus, the nervous gene action respects not only sagittal compartments delineated by two antibodies, but also rostro-caudal gradient. The cause of the dominant survival of P-path positive cells awaits future study. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DEPT BIOMED SCI,WALTHAM,MA 02254. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NICHD NIH HHS [HD05515, HD21018]; NINDS NIH HHS [NS 24386] NR 27 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD MAR PY 1994 VL 19 IS 2 BP 167 EP 174 DI 10.1016/0168-0102(94)90140-6 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NC790 UT WOS:A1994NC79000007 PM 8008245 ER PT J AU CUNNINGHAM, JJ AF CUNNINGHAM, JJ TI NX6.25 - RECOGNIZING A BIVARIATE EXPRESSION FOR PROTEIN BALANCE IN HOSPITALIZED-PATIENTS SO NUTRITION LA English DT Article ID NITROGEN-BALANCE; SUBSTRATE; INFUSION C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,SURG SERV,BOSTON,MA 02114. RP CUNNINGHAM, JJ (reprint author), UNIV MASSACHUSETTS,DEPT NUTR,201 CHENOWETH LAB,AMHERST,MA 01003, USA. NR 29 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 0899-9007 J9 NUTRITION JI Nutrition PD MAR-APR PY 1994 VL 10 IS 2 BP 124 EP 127 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NH756 UT WOS:A1994NH75600002 PM 8025364 ER PT J AU MORSTYN, G BROWN, S GORDON, M CRAWFORD, J DEMETRI, G RICH, W MCGUIRE, B FOOTE, M MCNIECE, I AF MORSTYN, G BROWN, S GORDON, M CRAWFORD, J DEMETRI, G RICH, W MCGUIRE, B FOOTE, M MCNIECE, I TI STEM-CELL FACTOR IS A POTENT SYNERGISTIC FACTOR IN HEMATOPOIESIS SO ONCOLOGY LA English DT Article DE STEM CELL FACTOR; R-METHUSCF; SYNERGISTIC ACTION; CLINICAL STUDIES; PRECLINICAL STUDIES; PERIPHERAL BLOOD PROGENITOR CELL MOBILIZATION; LETHAL-IRRADIATION PROTECTION ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; TYROSINE KINASE RECEPTOR; C-KIT LIGAND; PROTO-ONCOGENE; DRUG-THERAPY; MAST-CELLS; W-LOCUS; GROWTH; MOUSE AB Stem cell factor (SCF), a ligand for c-kit, has a broad range of activities including effects on cells at or near the level of the multipotential stem cell as well as on committed cells. Preclinical studies show that SCF can protect against lethal irradiation, elicit multilineage responses in peripheral blood and bone marrow cellularity, and increase circulating peripheral blood progenitor cells (PBPC) in a dose-dependent manner. Recombinant human SCF has major clinical potential through its synergy with other factors, especially recombinant human granulocyte colony-stimulating factor, to enhance mobilization of PBPC. C1 INDIANA UNIV,MED CTR,INDIANAPOLIS,IN. DUKE UNIV,DURHAM,NC. DANA FARBER CANC INST,BOSTON,MA. RP MORSTYN, G (reprint author), AMGEN INC,1840 DEHAVILLAND DR,THOUSAND OAKS,CA 91320, USA. NR 50 TC 43 Z9 44 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY JI Oncology PD MAR-APR PY 1994 VL 51 IS 2 BP 205 EP 214 PG 10 WC Oncology SC Oncology GA MY058 UT WOS:A1994MY05800011 PM 7515171 ER PT J AU AKOVA, YA FOSTER, CS AF AKOVA, YA FOSTER, CS TI CATARACT-SURGERY IN PATIENTS WITH SARCOIDOSIS-ASSOCIATED UVEITIS SO OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR-LENS IMPLANTATION; OCULAR SARCOIDOSIS; EXTRACTION; DIAGNOSIS; DISEASE AB Purpose: The authors analyzed the incidence of cataract development and the visual outcome of cataract surgery performed on patients with sarcoidosis-associated uveitis who were treated at the Immunology Service at the Massachusetts Eye and Ear Infirmary during a 17-year period. Methods: The records of 102 patients with sarcoidosis-associated uveitis who were treated with topical and regional corticosteroids, systemic nonsteroidal anti-inflammatory drugs, systemic steroids, or with systemic immunosuppressive chemotherapy were reviewed. Cataract surgery was performed on those eyes in which cataract developed, resulting in decreased visual acuity of 20/100 or less. The incidence of cataract development and visual results of cataract extraction and intraocular lens implantation were analyzed. Results: In this cohort of 102 patients, visually significant cataracts that warranted surgery developed in 10(16 eyes). In addition, four patients (5 eyes) had a visually significant cataract at the time of first evaluation. A total of 14 patients (21 eyes) underwent cataract surgery. Posterior chamber lens implantation accompanied cataract surgery in 19 (90.5%) of 21 eyes. The average final visual acuity of the 21 eyes after cataract surgery was 20/51, and 61% of the eyes achieved a stable visual acuity of 20/40 or better. The major causes of the decreased visual acuity in patients who had less than 20/40 visual acuity were sequelae of chronic posterior uveitis, cystoid macular edema, epiretinal membrane, and glaucomatous optic nerve damage. Conclusion: Posterior chamber lens implantation and cataract surgery in patients with sarcoidosis-associated uveitis can be well tolerated when absolute control of the inflammation is achieved. Pre-existing retinal pathology and glaucoma as a result of uncontrolled inflammation resulting in permanent ocular structural damage were found to be the most important factors for determining the postoperative final visual acuity. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,IMMUNOL SERV,BOSTON,MA 02114. ANKARA HOSP,DEPT OPHTHALMOL,ANKARA,TURKEY. NR 36 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1994 VL 101 IS 3 BP 473 EP 479 PG 7 WC Ophthalmology SC Ophthalmology GA NB220 UT WOS:A1994NB22000020 PM 8127567 ER PT J AU HOPEROSS, M YANNUZZI, LA GRAGOUDAS, ES GUYER, DR SLAKTER, JS SORENSON, JA KRUPSKY, S ORLOCK, DA PULIAFITO, CA AF HOPEROSS, M YANNUZZI, LA GRAGOUDAS, ES GUYER, DR SLAKTER, JS SORENSON, JA KRUPSKY, S ORLOCK, DA PULIAFITO, CA TI ADVERSE REACTIONS DUE TO INDOCYANINE GREEN SO OPHTHALMOLOGY LA English DT Article ID ANGIOGRAPHY AB Background: Although adverse reactions to indocyanine green (ICG) are known to occur, the dye has been used for more than 30 years in tests of cardiac and hepatic function, with a high level of safety. Improved digital video technology has renewed interest in the use of intravenous ICG in ophthalmic imaging. This report describes the authors' experience regarding the safety of ICG for digital angiography and their recommendations for its use in the ophthalmic setting. Methods: Digital ICG videoangiography was performed in 1226 consecutive patients, and 1923 ICG videoangiography tests were performed. A registry of adverse reactions to ICG was established. Criteria were used to define mild, moderate, and severe adverse reactions, and these data were recorded for every ICG study perf ormed. Results: There were three (0.15%) mild adverse reactions, four (0.2%) moderate reactions, and one (0.05%) severe adverse reaction. There were no deaths. Conclusions: This study documents the safety of intravenous ICG for use in ophthalmic videoangiography. C1 MANHATTAN EYE EAR & THROAT HOSP,LUESTHER T MERTZ RETINAL RES LAB,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. NR 24 TC 210 Z9 215 U1 0 U2 11 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 1994 VL 101 IS 3 BP 529 EP 533 PG 5 WC Ophthalmology SC Ophthalmology GA NB220 UT WOS:A1994NB22000027 PM 8127574 ER PT J AU LEVIN, LA JOSEPH, MP RIZZO, JF LESSELL, S AF LEVIN, LA JOSEPH, MP RIZZO, JF LESSELL, S TI OPTIC CANAL DECOMPRESSION IN INDIRECT OPTIC-NERVE TRAUMA SO OPHTHALMOLOGY LA English DT Article ID NEUROPATHY AB Background: The proper management of neurogenic visual loss after blunt head trauma is controversial. Non-treatment, corticosteroids, and surgical decompression of the optic canal are all currently considered to be reasonable alternatives. The goal of this study was to identify factors affecting improvement in patients treated with canal decompression. Methods: A retrospective analysis of 31 cases in which transethmoidal decompression of the optic canal had been performed for neurogenic visual loss after closed head trauma was conducted. Each patient was alert and free of injury to the globe when evaluated before surgery. Surgery was performed within 6 days of injury, and all were given perioperative steroids. Results: Visual acuity improved in 22 (71%) patients, with 6 (19%) regaining visual acuity of 20/40 or better. The mean improvement from preoperative visual deficit was 42.0% +/- 6.6%, with a median improvement of 45.2%. Both univariate and multivariate analysis suggested that vision improved more in patients who were younger than 40 years of age than in patients who were 40 years of age or older. Interval between injury and surgery, preoperative visual acuity, and the presence of optic canal fracture did not affect outcome. Conclusion: Any future randomized trials of therapy should stratify patients based on age. Enrollment of patients with no light perception or who experienced delay between injury and treatment may be reasonably considered. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,NEUROOPHTHALMOL UNIT,BOSTON,MA 02114. NR 13 TC 45 Z9 51 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 MAR PY 1994 VL 101 IS 3 BP 566 EP 569 PG 4 WC Ophthalmology SC Ophthalmology GA NB220 UT WOS:A1994NB22000032 PM 8127578 ER PT J AU LOCKHART, PB CLARK, J AF LOCKHART, PB CLARK, J TI PRETHERAPY DENTAL STATUS OF PATIENTS WITH MALIGNANT CONDITIONS OF THE HEAD AND NECK SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID ADJUVANT CHEMOTHERAPY; CANCER; RADIOTHERAPY AB Maxillofacial problems after radiotherapy to this region are common and have at least a temporal relationship to preexisting odontogenic disease. This study was undertaken to determine the dental status of patients before multimodality therapy for head and neck cancer. One hundred thirty-one patients were examined during their initial visit to a head and neck tumor clinic. The majority of dentulous patients were noncompliant with routine dental care (76%) and oral hygiene (65%). There was a high incidence of alveolar bone loss (66%), clinical caries (71%), and failing restorations (91%). Overall, 73 (97%) of the dentulous patients needed dental care before radiotherapy; however, follow-up visits revealed that 59 (81%) of these patients did not seek the indicated treatment. These data suggest that thorough oral examinations should be performed on all patients before radiotherapy that involves the oral cavity. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP LOCKHART, PB (reprint author), CAROLINAS MED CTR,DEPT DENT,POB 32861,CHARLOTTE,NC 28232, USA. NR 15 TC 37 Z9 38 U1 0 U2 1 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 MAR PY 1994 VL 77 IS 3 BP 236 EP 241 DI 10.1016/0030-4220(94)90291-7 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ND066 UT WOS:A1994ND06600005 PM 8170653 ER PT J AU SACHS, DH AF SACHS, DH TI THE PIG AS A XENOGRAFT DONOR SO PATHOLOGIE BIOLOGIE LA English DT Article; Proceedings Paper CT Symposium: Lilly Conferences Xenografting CY OCT 12, 1993 CL PARIS, FRANCE DE XENOGRAFT; MINIATURE SWINE; MIXED CHIMERISM; TOLERANCE ID NONLETHAL PREPARATIVE REGIMEN; TRANSPLANTATION; TOLERANCE; CHIMERISM 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 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 allogenic 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,SCH MED,BOSTON,MA 02129, USA. NR 17 TC 76 Z9 76 U1 0 U2 4 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 0369-8114 J9 PATHOL BIOL JI Pathol. Biol. PD MAR PY 1994 VL 42 IS 3 BP 217 EP 219 PG 3 WC Pathology SC Pathology GA NH165 UT WOS:A1994NH16500006 PM 8090569 ER PT J AU LIPSHULTZ, SE SANDERS, SP GOORIN, AM KRISCHER, JP SALLAN, SE COLAN, SD AF LIPSHULTZ, SE SANDERS, SP GOORIN, AM KRISCHER, JP SALLAN, SE COLAN, SD TI MONITORING FOR ANTHRACYCLINE CARDIOTOXICITY SO PEDIATRICS LA English DT Article DE ANTHRACYCLINE THERAPY; CARDIOTOXICITY; SERIAL CARDIAC MONITORING; CANCER PATIENTS; PEDIATRIC ID CONGESTIVE HEART-FAILURE; DOXORUBICIN THERAPY; CONTRACTILITY; CHILDHOOD; CHEMOTHERAPY; ADRIAMYCIN; MECHANICS; CHILDREN; EXERCISE; LEUKEMIA AB Objective. To review the basis for recommendations of the Cardiology Committee of the Children's Cancer Study Group, published in Pediatrics, for serial cardiac monitoring of cancer patients during anthracycline therapy and reduction of therapy should cardiac studies show abnormalities. Design. Because the effects of overall morbidity and mortality should be considered when a recommendation is made to withhold potentially lifesaving chemotherapy based on abnormal cardiac findings of patients without clinical evidence of cardiac dysfunction, supporting studies referenced in the published recommendations were reviewed. Specifically, studies were evaluated to determine whether a reduction in anthracycline dose, as a result of abnormal cardiac findings by monitoring, reduced cardiac morbidity and related mortality compared with a prospectively followed control population without dose modification. In addition, the effects of cardiac monitoring and subsequent anthracycline dose modification on oncologic morbidity and mortality were reviewed in these studies. Finally, the contributions of the cardiac and oncologic effects of dose modification were examined to determine the effect of this change in therapy on overall morbidity and mortality. Results. None of the studies cited in developing these recommendations prospectively determined, with controls, the effects of cardiac monitoring and anthracycline dose modification on cardiac, oncologic, or overall morbidity and mortality. Therefore, none of the studies cited in support of cardiac monitoring and subsequent dose reduction demonstrated the efficacy of such an approach. In the absence of such data, concerns are raised as to whether such a monitoring program with subsequent dose modification might do more harm than good. In addition, none of the methods of screening for anthracycline cardiotoxicity has been shown to be adequately predictive of early or late cardiac outcomes. Finally, adoption of these recommendations would inhibit the investigation of the efficacy of the proposed plan. Conclusion. Given the absence of supportive data and the potential to do harm, no recommendation for dose modification based on abnormal cardiac findings in patients without clinical evidence of cardiotoxicity can be endorsed, including those of the Cardiology Committee of the Children's Cancer Study Group. When clinical evidence of cardiotoxicity is present, anthracycline dose modification is recommended. A prospective controlled study to determine the effects of dose modification based on cardiac test results is indicated. C1 CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA. UNIV FLORIDA,COLL MED,DEPT PEDIAT,GAINESVILLE,FL. RP LIPSHULTZ, SE (reprint author), CHILDRENS HOSP,DEPT CARDIOL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. OI Sanders, Stephen/0000-0003-3521-4044 FU NCI NIH HHS [CA06516, CA29139, CA34183] NR 18 TC 93 Z9 97 U1 0 U2 1 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 MAR PY 1994 VL 93 IS 3 BP 433 EP 437 PG 5 WC Pediatrics SC Pediatrics GA MY687 UT WOS:A1994MY68700015 PM 7818624 ER PT J AU PERRIN, JM KAHN, RS BLOOM, SR DAVIDSON, S GUYER, B HOLLINSHEAD, W RICHMOND, JB WALKER, DK WISE, PH AF PERRIN, JM KAHN, RS BLOOM, SR DAVIDSON, S GUYER, B HOLLINSHEAD, W RICHMOND, JB WALKER, DK WISE, PH TI HEALTH-CARE REFORM AND THE SPECIAL NEEDS OF CHILDREN SO PEDIATRICS LA English DT Editorial Material ID UNITED-STATES; PRENATAL-CARE; PREVENTIVE CARE; MEDICAL-CARE; INJURIES; ACCESS; SYSTEM C1 CHILDRENS HOSP, BOSTON, MA USA. BOSTON UNIV, SCH MANAGEMENT, BOSTON, MA 02215 USA. JOHNS HOPKINS UNIV, DEPT MATERNAL & CHILD HLTH, BALTIMORE, MD USA. RHODE ISL DEPT HLTH, PROVIDENCE, RI USA. HARVARD UNIV, SCH MED, CAMBRIDGE, MA 02138 USA. MASSACHUSETTS DEPT PUBL HLTH, BOSTON, MA USA. RP PERRIN, JM (reprint author), MASSACHUSETTS GEN HOSP, WACC 715, BOSTON, MA 02114 USA. NR 24 TC 13 Z9 13 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD MAR PY 1994 VL 93 IS 3 BP 504 EP 506 PG 3 WC Pediatrics SC Pediatrics GA MY687 UT WOS:A1994MY68700027 PM 8115214 ER PT J AU CHANOCK, SJ LUGINBUHL, LM MCINTOSH, K LIPSHULTZ, SE AF CHANOCK, SJ LUGINBUHL, LM MCINTOSH, K LIPSHULTZ, SE TI LIFE-THREATENING REACTION TO TRIMETHOPRIM/SULFAMETHOXAZOLE IN PEDIATRIC HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO PEDIATRICS LA English DT Note ID PNEUMOCYSTIS-CARINII PNEUMONIA; TRIMETHOPRIM-SULFAMETHOXAZOLE; ORAL DESENSITIZATION; CO-TRIMOXAZOLE; HYPERSENSITIVITY REACTIONS; ASEPTIC-MENINGITIS; CHILDREN; AIDS; PATIENT C1 CHILDRENS HOSP,DIV INFECT DIS,BOSTON,MA. CHILDRENS HOSP,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA. CHILDRENS HOSP,DEPT CARDIOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NCRR NIH HHS [5 MO1RR02172]; NHLBI NIH HHS [R01HL48012-01]; NIAID NIH HHS [U01AI25934] NR 32 TC 24 Z9 25 U1 0 U2 1 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 MAR PY 1994 VL 93 IS 3 BP 519 EP 521 PG 3 WC Pediatrics SC Pediatrics GA MY687 UT WOS:A1994MY68700034 PM 8115221 ER PT J AU SANKEY, SL FRIEDMAN, LS AF SANKEY, SL FRIEDMAN, LS TI FORMULARY MANAGEMENT OF ANTIULCER DRUGS - CLINICAL CONSIDERATIONS SO PHARMACOECONOMICS LA English DT Article AB Peptic ulcer disease (PUD) is thought to result from an imbalance between aggressive (excessive) [especially gastric acid and pepsin] and protective (diminished) factors (gastric mucus and bicarbonate, prostaglandins and others) in the stomach. Recent attention has focused on the role of Helicobacter pylori as a cause of chronic active gastritis and a pathogenic factor in PUD. Antiulcer medications with proven efficacy in the treatment of acute PUD include histamine2 (H-2)-receptor antagonists, H+/K+-ATPase (proton pump) inhibitors, antacids, sucralfate and prostaglandin analogues. The advent of proton pump inhibitors in particular has resulted in effective therapy for ulcers that previously would have been considered refractory. H-2-receptor antagonists and sucralfate are also useful for maintenance therapy of PUD. Recent interest has focused on strategies aimed at eradicating H. pylori and the ensuing change in the natural history of PUD, specifically a marked decrease in ulcer recurrence. In contrast, with standard treatment regimens there is a high rate of ulcer relapse (50 to 90%) after acute ulcer healing. Eradication of H. pylori has until now required a triple drug regimen of bismuth and 2 antibiotics, and is too cumbersome for routine use. It is likely, however, that treatment aimed at eradicating H. pylori will be routine in the near future and will represent a cost-effective alternative to standard long term maintenance therapy. C1 MASSACHUSETTS GEN HOSP,DIV GASTROINTESTINAL,FRUIT ST,SUITE 404,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-7690 J9 PHARMACOECONOMICS JI Pharmacoeconomics PD MAR PY 1994 VL 5 IS 3 BP 213 EP 226 PG 14 WC Economics; Health Care Sciences & Services; Health Policy & Services; Pharmacology & Pharmacy SC Business & Economics; Health Care Sciences & Services; Pharmacology & Pharmacy GA NE112 UT WOS:A1994NE11200005 PM 10146896 ER PT J AU HARDIN, TC BUTLER, SC ROSS, S WAKEFORD, JH JORGENSEN, JH AF HARDIN, TC BUTLER, SC ROSS, S WAKEFORD, JH JORGENSEN, JH TI COMPARISON OF AMPICILLIN-SULBACTAM AND TICARCILLIN-CLAVULANIC ACID IN PATIENTS WITH CHRONIC-RENAL-FAILURE - EFFECTS OF DIFFERENTIAL PHARMACOKINETICS ON SERUM BACTERICIDAL ACTIVITY SO PHARMACOTHERAPY LA English DT Article ID TISSUE PENETRATION; PHARMACOLOGY AB Study Objectives. To evaluate the pharmacodynamic antibacterial activity of ticarcillin-clavulanic acid (T-C) and ampicillin-sulbactam (A-S) combinations against reference bacterial strains in patients with end-stage renal disease maintained on long-term hemodialysis. Design. Randomized, crossover, controlled study. Setting. National Institutes of Health-funded general clinical research unit in a Veterans Administration Medical Center. Patients. Nine adult men with end-stage renal disease maintained on long-term hemodialysis. Two subjects did not complete the study due to problems of vascular access, and another withdrew for personal reasons. Interventions. On a nondialysis day, each subject was randomly administered either T-C 3.1 g or A-S 3 g as a slow intravenous infusion over 30 minutes. Serial blood samples were collected for measurement of antibiotic serum concentrations and determination of serum bactericidal titers. Following a washout period, the study was repeated with the alternative antibiotic combination. Measurements and Main Results. The mean observed apparent beta-half-life of clavulanic acid was substantially shorter than that for the other three drugs. The bactericidal activity of both A-S and T-C against non-beta-lactamase-producing (Nbeta-LP) strains of S. aureus and E. coli was consistently high, as indicated by geometric mean SBTs of at least 1:5 at 24 hours. Against beta-lactamase-producing (beta-LP) S. aureus, the geometric mean SBTs for A-S were at least 1:25 throughout the study period, while the geometric mean SBTs for T-C decreased over 24 hours from 1:29 to 1:6. Against beta-LP E. coli, the bactericidal activities for both A-S and T-C were poor, with geometric mean peak SBTs of only 1:6 and 1:3, respectively. The geometric mean SBT for T-C against this E. coli strain had declined to 1:1 at 6 hrs. Conclusion. Increasing the dosing interval for T-C in patients with end-stage renal disease may lead to periods of insufficient clavulanic acid to protect ticarcillin from beta-lactamase degradation. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. 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. FU NCRR NIH HHS [M01-RR-01346] NR 11 TC 11 Z9 11 U1 0 U2 3 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 MAR-APR PY 1994 VL 14 IS 2 BP 147 EP 152 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ND068 UT WOS:A1994ND06800003 PM 8197032 ER PT J AU AVELINE, B HASAN, T REDMOND, RW AF AVELINE, B HASAN, T REDMOND, RW TI PHOTOPHYSICAL AND PHOTOSENSITIZING PROPERTIES OF BENZOPORPHYRIN DERIVATIVE MONOACID RING-A (BPD-MA) SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID QUANTUM YIELDS; PROTOPORPHYRIN-IX; SINGLET OXYGEN; TRIPLET-STATE; HEMATOPORPHYRIN; MODEL; LUMINESCENCE; FLUORESCENCE; BENZOPHENONE; SENSITIZERS AB The photophysical properties of benzoporphyrin derivative monoacid ring A (BPD-MA), a second-generation photosensitizer currently in phase II clinical trials, were investigated in homogeneous solution. Absorption, fluorescence, triplet-state, singlet oxygen (O-2 ((1) Delta(g))) sensitization studies and photobleaching experiments are reported. The ground state of this chlorin-type molecule shows a strong absorbance in the red (lambda approximate to 688 nm, epsilon approximate to 33 000 M(-1) cm(-1) in organic solvents). For the singlet excited state the following data were determined in methanol: energy level, E(S) = 42.1 kcal mol(-1), lifetime, tau(f) = 5.2 ns and fluorescence quantum yield, Phi(f) = 0.05 in air-saturated solution. The triplet state of BPD-MA has a lifetime, tau(T) greater than or equal to 25 mu s, an energy level, E(T) = 26.9 kcal mol(-1) and the molar absorption coefficient is epsilon T = 26 650 M(-1) cm(-1) at 720 nm. A dramatic effect of oxygen on the fluorescence (Phi(f)) and intersystem crossing (Phi(T)) quantum yields has been observed. The BPD-MA presents rather high triplet (Phi(T) = 0.68 under N-2-saturated conditions) and singlet oxygen (Phi(Delta) = 0.78) quantum yields. On the other hand, the presence of oxygen does not significantly modify the photobleaching of this photostable compound, the photodegradation quantum yield (Phi(Pb)) of which was found to be on the order of 5 x 10(-5) in organic solvents. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LAB PHOTOMED,BOSTON,MA 02114. NR 35 TC 145 Z9 150 U1 2 U2 22 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 MAR PY 1994 VL 59 IS 3 BP 328 EP 335 DI 10.1111/j.1751-1097.1994.tb05042.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NF318 UT WOS:A1994NF31800011 PM 8016212 ER PT J AU SHEEN, J AF SHEEN, J TI FEEDBACK-CONTROL OF GENE-EXPRESSION SO PHOTOSYNTHESIS RESEARCH LA English DT Review DE ACETATE; GLUCOSE; MAIZE; METABOLIC REPRESSION; PHOTOSYNTHETIC GENES; TRANSCRIPTION REGULATION ID TRANSGENIC TOBACCO PLANTS; CALVIN-CYCLE ENZYMES; RIBULOSE-1,5-BISPHOSPHATE CARBOXYLASE-OXYGENASE; ADP-GLUCOSE PYROPHOSPHORYLASE; SUCROSE-INDUCIBLE EXPRESSION; SINK-SOURCE INTERACTIONS; YEAST-DERIVED INVERTASE; MALATE SYNTHASE GENE; ALPHA-AMYLASE GENE; SACCHAROMYCES-CEREVISIAE AB Although feedback regulation of photosynthesis by carbon metabolites has long been recognized and investigated, its underlying molecular mechanisms remain unclear. The recent discovery that glucose and acetate trigger global repression of maize photosynthetic gene transcription provides the first direct evidence that a fundamental mechanism is used for feedback regulation of photosynthesis in higher plants. The metabolic repression of photosynthetic genes has now been found in many higher plants and is likely universal. It overrides other regulation by light, tissue type and developmental stage, and serves potentially as the molecular basis of interactions between sink and source tissues. Using simplified and convenient cellular systems and transgenic plants, the study of metabolic regulation of gene expression offers an excellent opportunity for the understanding of global and coordinate gene control and metabolite-mediated signal transduction in higher plants. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. RP SHEEN, J (reprint author), HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02114 USA. NR 118 TC 240 Z9 246 U1 2 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0166-8595 EI 1573-5079 J9 PHOTOSYNTH RES JI Photosynth. Res. PD MAR PY 1994 VL 39 IS 3 BP 427 EP 438 DI 10.1007/BF00014596 PG 12 WC Plant Sciences SC Plant Sciences GA NP930 UT WOS:A1994NP93000013 PM 24311134 ER PT J AU RIGOTTI, NA STOTO, MA SCHELLING, TC AF RIGOTTI, NA STOTO, MA SCHELLING, TC TI DO BUSINESSES COMPLY WITH A NO-SMOKING LAW - ASSESSING THE SELF-ENFORCEMENT APPROACH SO PREVENTIVE MEDICINE LA English DT Article ID PUBLIC PLACES; POLICIES; PREVALENCE; WORKSITES; WORKPLACE AB Background. Many states and cities have adopted laws restricting smoking in public places. Health departments generally regard the laws as self-enforcing, implying little need for monitoring or enforcement. Whether this achieves good compliance at the workplace, a major site of passive smoke exposure, is not known. Methods. We assessed workplace compliance with a no-smoking ordinance in Cambridge, Massachusetts, by conducting telephone surveys of two stratified random samples of city businesses, 3 and 24 months after the law took effect. Response rates were 76% at 3 months (n = 312) and 79% at 24 months (n = 317). Results. Employers' awareness and approval of the law were initially high. Approval remained high, but awareness declined over 2 years, from 92 to 73% (P < 0.0001), and employers' knowledge of the law's requirements was incomplete, Eighty percent of companies restricted smoking 3 and 24 months after the law, but only half of businesses fully complied with the law at either time. On multivariate analysis, compliance was significantly better in businesses that were aware of the law, in favor of it, and whose owners were nonsmokers. One fifth of firms with smoking policies cited the law as a reason for policy adoption. Conclusion. A self-enforcement approach to implementing a no-smoking law achieved high levels of awareness and intermediate levels of compliance in a city's businesses. Awareness of the law declined over 2 years without reinforcement. The law was popular with employers and was associated with a high level of smoking restrictions in city businesses, but further efforts are needed to maximize compliance with a no-smoking law and reduce workplace smoke exposure. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,JOHN F KENNEDY SCH GOVT,INST STUDY SMOKING BEHAV & POLICY,BOSTON,MA. RP RIGOTTI, NA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114, USA. NR 15 TC 12 Z9 14 U1 2 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD MAR PY 1994 VL 23 IS 2 BP 223 EP 229 DI 10.1006/pmed.1994.1030 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA NG964 UT WOS:A1994NG96400013 PM 8047529 ER PT J AU LITTMAN, AB DOWNING, J SCHEER, J AF LITTMAN, AB DOWNING, J SCHEER, J TI POOR RECOVERY IN YOUNG-WOMEN WITH CORONARY HEART-DISEASE SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. 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 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAR-APR PY 1994 VL 56 IS 2 BP 153 EP 153 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA NE119 UT WOS:A1994NE11900039 ER PT J AU DRAELOS, MT WEINGER, K SIMONSON, DC JACOBSON, AM AF DRAELOS, MT WEINGER, K SIMONSON, DC JACOBSON, AM TI GENDER DIFFERENCES IN COGNITIVE PERFORMANCE DURING HYPOGLYCEMIA AND HYPERGLYCEMIA IN PATIENTS WITH INSULIN-DEPENDENT DIABETES-MELLITUS (IDDM) SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. 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 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAR-APR PY 1994 VL 56 IS 2 BP 161 EP 161 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA NE119 UT WOS:A1994NE11900071 ER PT J AU COHENZEITZ, T JACOBSON, AM DEGROOT, M SAMSON, J AF COHENZEITZ, T JACOBSON, AM DEGROOT, M SAMSON, J TI IMPACT OF PSYCHIATRIC-ILLNESS ON QUALITY-OF-LIFE IN PATIENTS WITH TYPE-I AND TYPE-II DIABETES-MELLITUS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. MCLEAN HOSP,BELMONT,MA 02178. 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 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAR-APR PY 1994 VL 56 IS 2 BP 162 EP 162 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA NE119 UT WOS:A1994NE11900076 ER PT J AU DEGROOT, M JACOBSON, AM SAMSON, JA AF DEGROOT, M JACOBSON, AM SAMSON, JA TI PSYCHIATRIC-ILLNESS IN PATIENTS WITH TYPE-I AND TYPE-II DIABETES-MELLITUS SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAR-APR PY 1994 VL 56 IS 2 BP 176 EP 176 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA NE119 UT WOS:A1994NE11900133 ER PT J AU WEINGER, K DRAELOS, MT JACOBSON, AM SIMONSON, DC AF WEINGER, K DRAELOS, MT JACOBSON, AM SIMONSON, DC TI BLOOD-GLUCOSE ESTIMATION, SYMPTOMS, AND COGNITION IN INSULIN-DEPENDENT DIABETES-MELLITUS (IDDM) SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA. 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 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAR-APR PY 1994 VL 56 IS 2 BP 177 EP 177 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA NE119 UT WOS:A1994NE11900136 ER PT J AU RODBERG, G SURMAN, O KRADIN, R AF RODBERG, G SURMAN, O KRADIN, R TI EPINEPHRINE AUGMENTS THE T-CELL RESPONSE TO SOLUBLE-ANTIGEN IN A LOW-RESPONDER MOUSE STRAIN SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,CAMBRIDGE,MA 02138. 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 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAR-APR PY 1994 VL 56 IS 2 BP 179 EP 179 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA NE119 UT WOS:A1994NE11900143 ER PT J AU MURRAY, G AF MURRAY, G TI THE NEUROBEHAVIORAL TREATMENT OF EPILEPSY - MOSTOFSKY,DI, LOYNING,Y SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP MURRAY, G (reprint author), MASSACHUSETTS GEN HOSP,AVERY D WEISMAN MD PSYCHIAT CONSULTAT SERV,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 MAR-APR PY 1994 VL 35 IS 2 BP 166 EP 166 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA MY142 UT WOS:A1994MY14200012 ER PT J AU PALMER, WE AF PALMER, WE TI MR ARTHROGRAPHY OF THE LABRAL-LIGAMENTOUS COMPLEX OF THE SHOULDER - REPLY SO RADIOLOGY LA English DT Editorial Material ID GLENOID LABRUM; INJURIES; BICEPS; TEARS RP PALMER, WE (reprint author), MASSACHUSETTS GEN HOSP,DEPT BONE & JOINT RADIOL,WANG AMBULATORY CARE CTR,15 PARKMAN ST,STE 515,BOSTON,MA 02114, USA. NR 8 TC 1 Z9 1 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 MAR PY 1994 VL 190 IS 3 BP 644 EP 644 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MX698 UT WOS:A1994MX69800008 ER PT J AU PALMER, WE BROWN, JH ROSENTHAL, DI AF PALMER, WE BROWN, JH ROSENTHAL, DI TI LABRAL-LIGAMENTOUS COMPLEX OF THE SHOULDER - EVALUATION WITH MR ARTHROGRAPHY SO RADIOLOGY LA English DT Article DE MAGNETIC RESONANCE (MR), CONTRAST ENHANCEMENT; SHOULDER, ARTHROGRAPHY; SHOULDER, INJURIES; SHOULDER, MR ID GLENOID LABRUM; ANTERIOR DISLOCATION; GLENOHUMERAL JOINT; CT ARTHROGRAPHY; TEARS; STABILITY; INJURIES; BICEPS AB PURPOSE: To determine the usefulness of magnetic resonance (MR) arthrography in assessment of the labral-ligamentous complex and test the hypothesis that the inferior glenohumeral ligament (IGHL) is an important anatomic feature of clinical instability. MATERIALS AND METHODS: Forty-eight shoulders with labral diagnoses proved with arthroscopy or open surgery were prospectively examined with MR arthrography after intraarticular injection of gadopentetate dimeglumine. RESULTS: Surgical findings showed that 14 labra were normal, 24 were torn, and six were deficient. (One labrum was torn and deficient in separate locations.) MR arthrographic findings had a diagnostic sensitivity of 91% and specificity of 93%. In 32 patients with proved labral abnormalities, 30 lesions involved the labral-bicipital junction, origins of the glenohumeral ligaments, or both. In 22 of 23 shoulders considered clinically unstable, a labral abnormality involved the origin of the IGHL. CONCLUSION: MR arthrography accurately shows the relationship of labral lesions to the origins of the glenohumeral ligaments and helps in distinction between stable and unstable lesions. RP PALMER, WE (reprint author), MASSACHUSETTS GEN HOSP,DEPT BONE & JOINT RADIOL,WANG AMBULATORY CARE CTR,15 PARKMAN ST,STE 515,BOSTON,MA 02114, USA. NR 23 TC 197 Z9 200 U1 1 U2 6 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 1994 VL 190 IS 3 BP 645 EP 651 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MX698 UT WOS:A1994MX69800009 PM 8115604 ER PT J AU SILVERMAN, SG LEE, BY MUELLER, PR CIBAS, ES SELTZER, SE AF SILVERMAN, SG LEE, BY MUELLER, PR CIBAS, ES SELTZER, SE TI IMPACT OF POSITIVE FINDINGS AT IMAGE-GUIDED BIOPSY OF LYMPHOMA ON PATIENT-CARE - EVALUATION OF CLINICAL HISTORY, NEEDLE SIZE, AND PATHOLOGICAL FINDINGS ON BIOPSY PERFORMANCE SO RADIOLOGY LA English DT Article DE COMPUTED TOMOGRAPHY (CT), GUIDANCE; HODGKIN DISEASE, DIAGNOSIS, 99.8342; INTERVENTIONAL PROCEDURES; LYMPHOMA, DIAGNOSIS, 99.8342, 99.8343; LYMPHOMA, THERAPY, 99.8342, 99.8343; ULTRASOUND (US), GUIDANCE ID ASPIRATION BIOPSY; MALIGNANT-LYMPHOMA; HODGKINS-DISEASE; CORE BIOPSY; DIAGNOSIS; CYTOLOGY; NODES AB PURPOSE: To analyze the effect of findings at image-guided biopsy of abdominal lymphoma (IGBL) on patient care and define the key determinants of clinical success. MATERIALS AND METHODS: A retrospective, biinstitutional study was performed in 102 patients with positive or suspicious IGBL findings (93 patients with non-Hodgkin and nine patients with Hodgkin lymphoma). The proportion of patients treated on the basis of IGBL findings only was calculated and correlated with 10 determinants, including history of lymphoma, biopsy technique, needle size, immunocytochemical findings, and tumor grade. RESULTS: Overall, 73 patients (72%) were treated on the basis of biopsy findings Only, including 41 (91%) of 45 patients with a history of lymphoma and 32 (56%) of 57 patients with no such history (P <.01). No difference in findings existed when three needle-size groups were compared (P >.50). CONCLUSION: Whenever findings were positive, IGBL provided enough tissue to enable treatment in most patients. Fine needles were just as likely as larger needles to enable both determination of tumor grade and treatment. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. RP SILVERMAN, SG (reprint author), BRIGHAM & WOMENS HOSP,DEPT RADIOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 25 TC 43 Z9 44 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 MAR PY 1994 VL 190 IS 3 BP 759 EP 764 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MX698 UT WOS:A1994MX69800029 PM 8115624 ER PT J AU FRATACCI, MD KIMBALL, WR WAIN, JC GREENE, EM ZAPOL, WM AF FRATACCI, MD KIMBALL, WR WAIN, JC GREENE, EM ZAPOL, WM TI EFFECTS OF DIGOXIN ON REGIONAL DIAPHRAGM FUNCTION AFTER THORACOTOMY IN AWAKE SHEEP SO RESPIRATION PHYSIOLOGY LA English DT Article DE MAMMALS, SHEEP; MUSCLE, DIAPHRAGM; PHARMACOLOGICAL AGENTS, DIGOXIN, DIAPHRAGM CONTRACTION; PRESSURE, TRANS-DIAPHRAGMATIC ID STRENGTH GENERATION; MUSCLE; LENGTH; CONTRACTION; SURGERY AB The effects of digoxin on diaphragmatic contraction were studied in 12 sheep, within 6 days after a right thoracotomy, during the period of intense diaphragmatic inhibition. Diaphragmatic function was assessed by implanting sonomicrometry crystals and electromyographic (EMG) electrodes in both the costal and crural diaphragmatic regions. Awake sheep were studied before and after intravenous digoxin (0.04 mg/kg) during both quiet breathing (QB) and during CO2 rebreathing, until the fractional concentration of expired CO2 (FET(CO2)) reached 0.10. After digoxin infusion, during both QB and at FET(CO2) of 0.10, esophageal and transdiaphragmatic pressures increased (P<0.05). After digoxin infusion no changes were measured for end-expiratory resting length, shortening fraction, shortening velocity or EMG activity of either diaphragmatic segment or for respiratory frequency, ventilation, tidal volume and FET(CO2). We conclude that intravenous digoxin given to awake sheep after a thoracotomy increases P-di, but does not alter diaphragmatic shortening nor alter the level of diaphragmatic activation either during QB or at FET(CO2) of 0.10. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ANAESTHESIA LABS,BOSTON,MA 02114. NR 32 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD MAR PY 1994 VL 95 IS 3 BP 259 EP 271 DI 10.1016/0034-5687(94)90089-2 PG 13 WC Physiology; Respiratory System SC Physiology; Respiratory System GA MZ315 UT WOS:A1994MZ31500003 PM 8059071 ER PT J AU LEE, KS KIMURA, RS AF LEE, KS KIMURA, RS TI ULTRASTRUCTURAL-CHANGES OF THE VESTIBULAR SENSORY ORGANS AFTER STREPTOMYCIN APPLICATION ON THE LATERAL CANAL SO SCANNING MICROSCOPY LA English DT Article DE STREPTOMYCIN; LATERAL AMPULLA; VESTIBULAR TOXICITY; ULTRASTRUCTURAL CHANGES ID INNER-EAR AB Early changes in the vestibular sense organs resulting from the application of a streptomycin sulfate soaked Gelfoam(R) pledget on the fenestra of the lateral semicircular canal were studied by transmission and scanning electron microscopy. Three days after the application, lesions were present in the central part of the lateral crista. The type I sensory cells were more affected than the type II cells. These sensory cells showed mitochondrial swelling, cytoplasm protrusion at the cell apex, inclusion of multiple vacuoles, fusion or loss of stereocilia, and pyknotic nuclei. Seven days after the drug application, the sensory cell damage extended to all three cristae and macula utriculi. The lesions were very extensive after ten days and the sensory cells had almost equally disappeared in all three cristae; the lesion in the macula utriculi was smaller and the macula sacculi was unaffected. At fourteen days, the lesions appeared less severe. Thus, a single application of a small amount of streptomycin on the lateral canal fenestra affected all vestibular sense organs, except the saccule, in a short time. The strong affinity of aminoglycosides for the cristae suggests possible entrapment of the drug at the ampullae. This local drug application technique to the canal will be useful in studying vestibular function in animals, and it is applicable to controlling severe vestibular symptoms in human patients. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. UNIV ULSAN,COLL MED,ASAN MED CTR,DEPT OTOLARYNGOL,SEOUL,SOUTH KOREA. HARVARD UNIV,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02115. FU NIDCD NIH HHS [NIDCD DC00073] NR 20 TC 10 Z9 10 U1 0 U2 0 PU SCANNING MICROSCOPY INT PI CHICAGO PA PO BOX 66507, AMF O'HARE, CHICAGO, IL 60666 SN 0891-7035 J9 SCANNING MICROSCOPY JI Scanning Microsc. PD MAR PY 1994 VL 8 IS 1 BP 107 EP 124 PG 18 WC Microscopy SC Microscopy GA NZ933 UT WOS:A1994NZ93300013 PM 7973498 ER PT J AU TOLKOFFRUBIN, NE AF TOLKOFFRUBIN, NE TI WHAT ARE THE IMPORTANT CONSIDERATIONS IN THE CARE OF CRITICALLY ILL PATIENTS WITH ACUTE-RENAL-FAILURE SO SEMINARS IN DIALYSIS LA English DT Editorial Material RP TOLKOFFRUBIN, NE (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,HEMODIALYSIS & CARD UNITS,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAR-APR PY 1994 VL 7 IS 2 BP 103 EP 106 DI 10.1111/j.1525-139X.1994.tb00818.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA NC652 UT WOS:A1994NC65200005 ER PT J AU MUELLER, PR DAWSON, SL AF MUELLER, PR DAWSON, SL TI UPDATE IN INTERVENTIONAL NEURORADIOLOGY .2. SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP MUELLER, PR (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD MAR PY 1994 VL 11 IS 1 BP U1 EP U1 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NM908 UT WOS:A1994NM90800001 ER PT J AU THESSING, VC ANCH, AM MUEHLBACH, MJ WALSH, JK SCHWEITZER, PK AF THESSING, VC ANCH, AM MUEHLBACH, MJ WALSH, JK SCHWEITZER, PK TI 2-HOUR AND 4-HOUR BRIGHT-LIGHT EXPOSURES DIFFERENTIALLY EFFECT SLEEPINESS AND PERFORMANCE THE SUBSEQUENT NIGHT SO SLEEP LA English DT Article DE BRIGHT LIGHT; SHIFT WORK; CIRCADIAN RHYTHM; PERFORMANCE; SLEEPINESS ID HUMAN CIRCADIAN PACEMAKER; CORE BODY-TEMPERATURE; SHIFT WORK; RHYTHMS; ALERTNESS; ADAPTATION; TRIAZOLAM; EEG AB The effect of two durations of bright light upon sleepiness and performance during typical night shift hours was assessed. Thirty normal, healthy young adults participated in a 2-night protocol. On the Ist night subjects were exposed to bright or dim light beginning at 2400 hours, under one of the following three conditions: bright light for 4 hours, dim light for 2 hours followed by bright light for 2 hours or dim light for 4 hours. Following light exposure, subjects remained awake until 0800 hours in a dimly lit room and slept in the laboratory between 0800 and 1600 hours, during which time sleep was estimated with actigraphy. Throughout the 2nd night, the multiple sleep latency test (MSLT), simulated assembly line task (SALT) performance, and subjective sleepiness were recorded. The single, 4-hour exposure to bright light was found to significantly increase MSLT scores and improve SALT performance during the early morning hours on the night following bright-light exposure. No significant effects were noted with a 2-hour exposure. The most likely explanation for these findings is a phase delay in the circadian rhythm of sleepiness-alertness. C1 ST LOUIS UNIV,ST LOUIS,MO 63103. RP THESSING, VC (reprint author), DEACONNESS MED CTR,CTR SLEEP DISORDERS & RES,6150 OAKLAND AVE,ST LOUIS,MO 63139, USA. NR 21 TC 26 Z9 26 U1 1 U2 5 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 1610 14TH STREET NW SUITE 300, ROCHESTER, MN 55806 SN 0161-8105 J9 SLEEP JI Sleep PD MAR PY 1994 VL 17 IS 2 BP 140 EP 145 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NJ634 UT WOS:A1994NJ63400005 PM 8036368 ER PT J AU HISNANICK, JJ AF HISNANICK, JJ TI COMPARATIVE-ANALYSIS OF VIOLENT DEATHS IN AMERICAN-INDIANS AND ALASKA NATIVES SO SOCIAL BIOLOGY LA English DT Article ID UNITED-STATES; SUICIDE; HOMICIDE; FIREARM AB Accidents, injuries, and outcomes from adverse effects have been identified as the second leading cause of death for American Indians and Alaska Natives (AI/AN). However, no studies have been done which analyze violent deaths (homicides, suicides, and other accidents) for this population with a focus on time trends. For this study, overall and gender-specific mortality rates due to violent deaths were computed for 1973-88. The results indicate that overall and gender-specific mortality rates for violent deaths in AI/AN have been decreasing on average per year: homicide, 4.3%; suicide, 2.7%; other accidents, 5.6%. Similarly, age-adjusted rates have been declining, and at faster rates than those of the U.S. general population: homicide, 4.5% vs. 1.4%; suicide, 2.5% vs. 0.6%; other accidents, 6.2% vs. 2.6%. However, the male-female ratio for homicides and other accidents has remained unchanged, and the ratio for suicide has been increasing. While the gap between age-adjusted rates have been narrowing, the age-adjusted rates for AI/AN have remained consistently above those of the U.S. general population. RP HISNANICK, JJ (reprint author), US DEPT VET AFFAIRS,DIV BIOMETR 008C12,WASHINGTON,DC 20420, USA. NR 19 TC 5 Z9 5 U1 0 U2 2 PU SOC STUDY SOCIAL BIOLOGY PI PORT ANGELES PA P O BOX 2349, PORT ANGELES, WA 98362 SN 0037-766X J9 SOC BIOL JI Soc. Biol. PD SPR-SUM PY 1994 VL 41 IS 1-2 BP 96 EP 109 PG 14 WC Demography; Social Sciences, Biomedical; Sociology SC Demography; Biomedical Social Sciences; Sociology GA PG814 UT WOS:A1994PG81400007 PM 7973844 ER PT J AU TEMPLE, HT KRUSE, RW VANDAM, BE AF TEMPLE, HT KRUSE, RW VANDAM, BE TI LUMBAR AND LUMBOSACRAL FUSION USING STEFFEE INSTRUMENTATION SO SPINE LA English DT Article DE LUMBAR FUSION; PEDICLE SCREWS; STEFFEE PLATES AB Posterior and posterolateral spinal fusion with the Steffee variable plating system have been performed on 176 patients at Walter Reed Army Medical Center since November 1985. This report covers the authors' early experience using the Steffee device on 39 patients. All of the 39 patients (100%) were available for a minimum follow-up of 2 years. Complications occurred in 26% of the patients. Radiographic pseudarthrosis occurred in 8% of the patients. The findings suggest that lumbar and lumbosacral fusion supplemented with Steffee plate instrumentation are associated with a low incidence of pseudarthrosis and acceptable morbidity overall. RP TEMPLE, HT (reprint author), MASSACHUSETTS GEN HOSP,3200 FRUIT ST,GRAY BLDG,6TH FLR,BOSTON,MA 02114, USA. NR 0 TC 19 Z9 21 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-2436 J9 SPINE JI SPINE PD MAR 1 PY 1994 VL 19 IS 5 BP 537 EP 541 DI 10.1097/00007632-199403000-00008 PG 5 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA NA418 UT WOS:A1994NA41800008 PM 8184347 ER PT J AU HOLMES, LB HARVEY, EA BROWN, KS HAYES, AM KHOSHBIN, S AF HOLMES, LB HARVEY, EA BROWN, KS HAYES, AM KHOSHBIN, S TI ANTICONVULSANT TERATOGENESIS .1. A STUDY DESIGN FOR NEWBORN-INFANTS SO TERATOLOGY LA English DT Article ID FETAL AB The basis for the apparent teratogenicity of maternal epilepsy is controversial. Is the critical factor the anticonvulsant drugs taken by the pregnant woman, or the genes which cause the mother's epilepsy? We describe a study design developed to assess these competing theories in a cohort study of newborn infants. We show the feasibility of ascertaining exposed and unexposed infants at several birthing hospitals in one urban area. Between 1986 and 1988, we identified 180 drug-exposed and 218 epilepsy-history infants among 49,403 infants. The rote of exposure to seizure medication was 0.36% and of maternal history of epilepsy was 0.44%. A significant number of infants could not be evaluated because they were missed, ineligible, or either the doctor, nurse or parent refused to participate. Overall, there was a significant increase in major malformations, microcephaly or growth retardation among the drug-exposed infants in comparison to both the epilepsy-history and the unexposed infants. The types of epilepsy and the apparent etiology were the same among women who took anticonvulsants and women with a history of epilepsy but no anticonvulsants during pregnancy. This study must be extended to include a sufficient number of infants exposed to each commonly used drug as monotherapy to allow for a comparison of the effect of each drug on pregnancy outcomes, to provide a comparison of infants whose mothers had a strong family history of epilepsy with infants whose mothers had trauma-induced epilepsy; and to assess the possible impact of the severity of the mothers' disease on the infants. (C) 1994 Wiley Liss, Inc. C1 BRIGHAM & WOMENS HOSP,DEPT NEUROL,BOSTON,MA 02115. RP HOLMES, LB (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS SERV,GENET & TERATOL UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS 24125] NR 13 TC 37 Z9 37 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD MAR PY 1994 VL 49 IS 3 BP 202 EP 207 DI 10.1002/tera.1420490316 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA ND258 UT WOS:A1994ND25800015 PM 8059427 ER PT J AU MCCULLOUGH, LB ASHTON, CM AF MCCULLOUGH, LB ASHTON, CM TI A METHODOLOGY FOR THE TEACHING ETHICS IN THE CLINICAL SETTING - A CLINICAL HANDBOOK FOR MEDICAL-ETHICS SO THEORETICAL MEDICINE LA English DT Article DE BIOETHICS; CLINICAL ETHICS; TEACHING; HANDBOOK; PREVENTIVE ETHICS AB The pluralism of methodologies and severe time constraints pose important challenges to pedagogy in clinical ethics. We designed a step-by-step student handbook to operate within such constraints and to respect the methodological pluralism of bioethics and clinical ethics. The handbook comprises six steps: Step 1: What are the facts of the case?; Step 2: What are your obligations to your patient?; Step 3: What are your obligations to third parties to your relationship with the patient?; Step 4: Do your obligations converge or conflict?; Step 5: What is the strongest objection that could be made to the identification of convergence in step 4 or the arguments in step 4? How can this objection be effectively countered?; and Step 6: How could the ethical conflict, or perceived ethical conflict, have been prevented? C1 HOUSTON VET AFFAIRS MED CTR,VET ADM HLTH SERV RES & DEV FIELD PROGRAM,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. RP MCCULLOUGH, LB (reprint author), BAYLOR COLL MED,CR ETHICS MED & PUBL ISSUES,1 BAYLOR PLAZA,HOUSTON,TX 77030, USA. NR 6 TC 18 Z9 18 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-9902 J9 THEOR MED JI Theor. Med. PD MAR PY 1994 VL 15 IS 1 BP 39 EP 52 DI 10.1007/BF00999218 PG 14 WC Medicine, Legal; Social Issues SC Legal Medicine; Social Issues GA NQ703 UT WOS:A1994NQ70300004 PM 8059431 ER PT J AU HERSHMAN, JM AF HERSHMAN, JM TI HIGHLIGHTS OF THIS ISSUE SO THYROID LA English DT Editorial Material RP HERSHMAN, JM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,BLDG 114,ROOM 200,WILSHIRE & SAWTELLE BLVDS,LOS ANGELES,CA 90073, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1050-7256 J9 THYROID JI Thyroid PD SPR PY 1994 VL 4 IS 1 BP 1 EP 1 DI 10.1089/thy.1994.4.1 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NJ425 UT WOS:A1994NJ42500001 ER PT J AU ANDERSON, KC AF ANDERSON, KC TI POTENTIAL ALTERNATIVES TO PLATELET TRANSFUSION SO TRANSFUSION SCIENCE LA English DT Article RP ANDERSON, KC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BLOOD COMPONENT LAB,44 BINNEY ST,BOSTON,MA 02115, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0955-3886 J9 TRANSFUS SCI JI Transfus. Sci. PD MAR PY 1994 VL 15 IS 1 BP 63 EP 65 DI 10.1016/0955-3886(94)90057-4 PG 3 WC Hematology SC Hematology GA NL216 UT WOS:A1994NL21600010 PM 10147200 ER PT J AU BONNERWEIR, S SMITH, FE AF BONNERWEIR, S SMITH, FE TI ISLET-CELL GROWTH AND THE GROWTH-FACTORS INVOLVED SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PANCREATIC MONOLAYER-CULTURES; FACTOR-I; PLACENTAL-LACTOGEN; ENDOCRINE PANCREAS; INSULIN-SECRETION; GENE-EXPRESSION; BETA-CELLS; RAT; HORMONE; GLUCOSE AB Throughout development, growth and aging, the mass of the pancreatic islets, in particular the insulin-producing beta cell, increases to meet the functional demand and maintain euglycemia. Islet growth occurs by two pathways: (a) the expansion by replication of preexisting beta cells and (b) the formation of new islets (neogenesis) by proliferation and subsequent differentiation of pancreatic ductal epithelium. Some of the factors involved in these pathways of islet growth have been defined. RP BONNERWEIR, S (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. OI Bonner-Weir, Susan/0000-0003-4682-0656 NR 44 TC 66 Z9 68 U1 0 U2 2 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 MAR PY 1994 VL 5 IS 2 BP 60 EP 64 DI 10.1016/1043-2760(94)90003-5 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NH562 UT WOS:A1994NH56200003 PM 18407189 ER PT J AU BEAL, MF HYMAN, BT KOROSHETZ, W AF BEAL, MF HYMAN, BT KOROSHETZ, W TI PATHOGENESIS OF HUNTINGTONS-DISEASE - REPLY SO TRENDS IN NEUROSCIENCES LA English DT Letter C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP BEAL, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 1994 VL 17 IS 3 BP 107 EP 108 DI 10.1016/0166-2236(94)90118-X PG 2 WC Neurosciences SC Neurosciences & Neurology GA NA301 UT WOS:A1994NA30100009 ER PT J AU OBERLEY, TD SEMPF, JM OBERLEY, MJ MCCORMICK, ML MUSE, KE OBERLEY, LW AF OBERLEY, TD SEMPF, JM OBERLEY, MJ MCCORMICK, ML MUSE, KE OBERLEY, LW TI IMMUNOGOLD ANALYSIS OF ANTIOXIDANT ENZYMES IN HUMAN RENAL-CELL CARCINOMA SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY LA English DT Article DE MANGANESE SUPEROXIDE DISMUTASE; NEOPLASIA; MITOCHONDRIA ID MANGANESE SUPEROXIDE-DISMUTASE; SYRIAN-HAMSTER TISSUES; FREE-RADICALS; IMMUNOHISTOCHEMICAL LOCALIZATION; KIDNEY DEVELOPMENT; TRANSGENIC MICE; TUMOR; PROLIFERATION; EXPRESSION; RADIATION AB Analysis of activities of the antioxidant enzyme manganese superoxide dismutase in human renal cell carcinomas often showed greatly altered enzyme levels (either elevated or depressed) compared to the cell of origin, the kidney proximal tubule. In order to better understand the variability observed, immunogold studies were performed on human renal cell carcinomas using a polyclonal antibody to human kidney manganese superoxide dismutase. For comparison, studies were also performed using antibodies to other antioxidant enzymes. For histologic studies, renal cell carcinomas were subclassified on the basis of light microscopy and ultrastructural analysis into clear cell, granular cell, or mixed clear and granular cell variants. In all three types of tumor, immunogold studies showed little staining using antibodies to copper, zinc superoxide dismutase or glutathione-dependent enzymes. However, intensity of labelling for manganese superoxide dismutase and catalase depended on the cell type(s) in the tumor. Clear cell variants demonstrated trace staining for manganese superoxide dismutase and catalase, while granular cell variants exhibited heavy staining for both of these enzymes. Mixed types of tumors showed clear cells with trace staining for all antioxidant enzymes examined, while granular cells again showed intense labelling for manganese superoxide dismutase and catalase. Using normal kidney proximal tubule as a comparison, immunogold ultrastructural analysis using antibody to manganese superoxide dismutase demonstrated infrequent small lightly labelled mitochondria in clear cell variants, while granular cell variants exhibited numerous medium-sized heavily labelled mitochondria. These data suggest that: 1) the variability in activity values for manganese superoxide dismutase may be due to heterogeneity of cell types in these tumors and 2) manganese superoxide dismutase immunoreactive protein was elevated in granular cells both because of an increase in number of mitochondria and because the labelling density in mitochondria was increased compared to mitochondria in clear cell types or in normal proximal tubular cells. C1 UNIV IOWA,COLL MED,RADIAT RES LAB,IOWA CITY,IA 52242. UNIV WISCONSIN,SCH MED,DEPT PATHOL,MADISON,WI 53706. RP OBERLEY, TD (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL & LAB MED SERV,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NCI NIH HHS [CA 41267] NR 43 TC 34 Z9 34 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. Int. J. Pathol. PD MAR PY 1994 VL 424 IS 2 BP 155 EP 164 PG 10 WC Pathology SC Pathology GA NZ498 UT WOS:A1994NZ49800006 PM 8180777 ER PT J AU MELEGARI, M BRUNO, S WANDS, JR AF MELEGARI, M BRUNO, S WANDS, JR TI PROPERTIES OF HEPATITIS-B VIRUS PRE-S1 DELETION MUTANTS SO VIROLOGY LA English DT Article ID CHRONIC HBV INFECTION; SURFACE-ANTIGEN PROMOTER; T-CELL; TRANSCRIPTION FACTOR; ENVELOPE PROTEINS; GENETIC-VARIATION; ESCAPE; REARRANGEMENTS; RECOGNITION; SEQUENCE AB Deletion mutants of hepatitis B virus (HBV) pre-S proteins were detected in serum in 2 of 10 (20%) individuals with chronic hepatitis B infection following the initiation of interferon treatment. The size of these deletions was up to one-half of the entire pre-S1 region. In vivo, all HBV deletion mutants were found to coexist with a full-length ''wild-type'' viral genome. The functional properties of a HBV-deleted mutant were studied in detail and revealed a stop codon in the pre-S2 open reading frame in all 20 of the clones sequenced. Several of the deleted mutants produced low-level HBsAg in culture supernatants compared to wild-type virus due to a putative loss of transcription factor binding sites. Transfection experiments in human hepatoma cells (HuH-7) demonstrated that the polymerase gene function was not affected by the large pre-S1 deletions and mutant viral genomes were capable of replication. However, secretion of incapsidated mutant viral genomes was blocked in HuH-7 cells. Cotransfection studies with a plasmid expressing only the HBV pre-S1, pre-S2, and S proteins resulted in complete restoration of viral particle secretion. Our findings suggest that an in vivo trans-complementation phenomenon would have had to occur to permit secretion from the liver into serum of the nucleocapsids containing these deleted viral genomes. (C) 1994 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. UNIV MILAN,DEPT INTERNAL MED,MILAN,ITALY. OI Bruno, Savino/0000-0002-3887-864X FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-00048, AA-08169] NR 32 TC 89 Z9 91 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 0042-6822 J9 VIROLOGY JI Virology PD MAR PY 1994 VL 199 IS 2 BP 292 EP 300 DI 10.1006/viro.1994.1127 PG 9 WC Virology SC Virology GA MY848 UT WOS:A1994MY84800005 PM 8122362 ER PT J AU AMES, A AF AMES, A TI STEADY-STATE FEEDBACK IN MAMMALIAN PHOTOTRANSDUCTION ILLUSTRATED BY A NOMOGRAM SO VISION RESEARCH LA English DT Article DE PHOTOTRANSDUCTION; ADAPTATION; CALCIUM; GUANYLATE CYCLASE; CGMP ID ROD OUTER SEGMENTS; GUANYLATE-CYCLASE; CYCLIC-GMP; VISUAL TRANSDUCTION; RETINAL RODS; FREE CALCIUM; LIGHT; PHOTORECEPTORS; TRANSPORT; CONES AB Published data characterizing the four reactions responsible for the Ca2+-mediated negative feedback in mammalian rod phototransduction were used to generate graphs which are combined in a circular fashion so that the y-axis of one serves as the x-axis of the next. The nomogram thus created makes it possible to determine by inspection the steady state situation in darkness, and tbe quasi-steady state situations that pertain shortly after exposure to light of different intensities. The results predicted by the nomogram suggest that Ca2+-mediated negative feedback is responsible for the Weber-Fechner relationship between stimulus and response. RP AMES, A (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,414 EDWARDS BLDG,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS 25753] NR 32 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0042-6989 J9 VISION RES JI Vision Res. PD MAR PY 1994 VL 34 IS 6 BP 821 EP 827 DI 10.1016/0042-6989(94)90219-4 PG 7 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA PH857 UT WOS:A1994PH85700010 PM 7512776 ER PT J AU STADTLANDER, CTKH MADOFF, S AF STADTLANDER, CTKH MADOFF, S TI CHARACTERIZATION OF CYTOPATHOGENICITY OF AQUARIUM SEAL MYCOPLASMAS AND SEAL FINGER MYCOPLASMAS BY LIGHT AND SCANNING ELECTRON-MICROSCOPY SO ZENTRALBLATT FUR BAKTERIOLOGIE-INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY VIROLOGY PARASITOLOGY AND INFECTIOUS DISEASES LA English DT Article ID PHOCA-VITULINA L; HARBOR SEALS; MASS MORTALITY; SP-NOV; MORBILLIVIRUS; MEMBRANES; PULMONIS; VIRUS; RATS AB Two recent mycoplasma isolates (one from an aquarium seal and one from a patient with the clinical entity known as seal finger) have been evaluated for cytopathogenicity in tracheal explant cultures. Examinations were performed in direct comparison to Mycoplasma phocidae, an isolate from an epidemic of seal pneumonia along the New England coast (USA) in 1979-1980. The study revealed similar inhibitory effects on ciliated tracheal epithelial cells and clumping of cilia by attached mycoplasmas; no exfoliation of respiratory epithelial cells was observed. In addition, cytopathic effects caused by the mycoplasmas were distinguished from effects of aging in non-infected explants under long-term in-vitro cultivation conditions. The general meaning of mycoplasmas in seals is discussed in detail in this paper. C1 UNIV ALABAMA,SCH MED,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH DENT,DEPT MICROBIOL,BIRMINGHAM,AL 35294. MASSACHUSETTS GEN HOSP,DEPT BACTERIOL,BOSTON,MA 02114. NR 27 TC 8 Z9 8 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0934-8840 J9 ZBL BAKT-INT J MED M JI Zent.bl. Bakteriol.-Int. J. Med. Microbiol. Virol. Parasitol. Infect. Dis. PD MAR PY 1994 VL 280 IS 4 BP 458 EP 467 PG 10 WC Microbiology; Virology SC Microbiology; Virology GA NF865 UT WOS:A1994NF86500005 PM 8061406 ER PT J AU RUBIN, RA FALESTINY, M MALET, PF AF RUBIN, RA FALESTINY, M MALET, PF TI CHRONIC HEPATITIS-C - ADVANCES IN DIAGNOSTIC TESTING AND THERAPY SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID NON-B-HEPATITIS; RECOMBINANT ALPHA-INTERFERON; AUTOIMMUNE CHRONIC HEPATITIS; NON-A; VIRUS-ANTIBODIES; VIRAL-RNA; MECHANISMS; SERUM; ALFA; HIV AB The methods for diagnosing hepatitis C virus infection have been evolving since the first-generation enzyme-linked immunosorbent assay antibody test was devised in 1989. In addition to assaying for serum antibodies against viral proteins, serum and liver tissue can be tested for viral RNA, evidence of ongoing viral replication. The improving ability to diagnose hepatitis C has furthered the understanding of the natural history of this infection. Acute hepatitis C results in chronic elevations of serum transaminase levels following nearly one half of cases. Cirrhosis complicates approximately 20% of chronic infections. Long-standing chronic hepatitis C may play a role in the pathogenesis of hepatocellular carcinoma. Sustained normalization of serum transaminase levels, often accompanied by a decrease in or disappearance of viral RNA, occurs in approximately 25% of patients with chronic hepatitis C who are treated with a 6-month course of recombinant interferon alfa. This treatment can occasionally be complicated by hematologic, endocrinologic, and psychiatric adverse effects but is usually fairly well tolerated. Whether interferon therapy will diminish the risk of cirrhosis or carcinoma is not yet known. This article reviews the diagnosis of chronic hepatitis C infection as well as the mechanisms of action, efficacy, and adverse effects associated with interferon alfa therapy. C1 HOSP UNIV PENN,PHILADELPHIA,PA 19104. MED COLL PENN,DEPT MED,PHILADELPHIA,PA 19129. RP RUBIN, RA (reprint author), VET AFFAIRS MED CTR,DIV GASTROENTEROL,PHILADELPHIA,PA 19104, USA. NR 33 TC 34 Z9 34 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 28 PY 1994 VL 154 IS 4 BP 387 EP 392 DI 10.1001/archinte.154.4.387 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA MY631 UT WOS:A1994MY63100005 PM 7509593 ER PT J AU SASAKI, Y WANDS, JR AF SASAKI, Y WANDS, JR TI ETHANOL IMPAIRS INSULIN-RECEPTOR SUBSTRATE-1 MEDIATED SIGNAL-TRANSDUCTION DURING RAT-LIVER REGENERATION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOSPHATIDYLINOSITOL 3'-KINASE; HEPATIC REGENERATION; GROWTH-FACTOR; FACTOR-I; EXPRESSION; PROTEIN; IRS-1; CELL; PHOSPHORYLATION; STIMULATION AB Chronic ethanol exposure inhibits the capacity of the liver to regenerate. Insulin is a potent hepatotrophic factor and it was determined if ethanol interferes with insulin receptor substrate (IRS-l)-protein mediated signal transduction during liver regeneration. Tyrosyl phosphorylation of IRS-1 was strikingly increased prior to the major wave of DNA synthesis in isocaloric pair-fed control rats; a blunted and delayed response was found in ethanol-fed rats. Enzymatic activity of phosphatidylinositol 3-kinase, a Src homology 2 (SH2) domain containing signal transduction molecule was enhanced by the association with tyrosyl phosphorylated IRS-1, whereas in ethanol-fed rats, this activity was greatly diminished and delayed. These results indicate that one potential molecular mechanism whereby ethanol inhibits hepatocyte DNA synthesis is through its action on the IRS-l-mediated signal transduction cascade. (C) 1994 Academic Press, Inc. RP SASAKI, Y (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA 02129, USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-00048, AA-02666] NR 30 TC 58 Z9 59 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 28 PY 1994 VL 199 IS 1 BP 403 EP 409 DI 10.1006/bbrc.1994.1243 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MY101 UT WOS:A1994MY10100060 PM 7510107 ER PT J AU BARONDES, SH CASTRONOVO, V COOPER, DNW CUMMINGS, RD DRICKAMER, K FEIZI, T GITT, MA HIRABAYASHI, J HUGHES, C KASAI, K LEFFLER, H LIU, FT LOTAN, R MERCURIO, AM MONSIGNY, M PILLAI, S POIRER, F RAZ, A RIGBY, PWJ RINI, JM WANG, JL AF BARONDES, SH CASTRONOVO, V COOPER, DNW CUMMINGS, RD DRICKAMER, K FEIZI, T GITT, MA HIRABAYASHI, J HUGHES, C KASAI, K LEFFLER, H LIU, FT LOTAN, R MERCURIO, AM MONSIGNY, M PILLAI, S POIRER, F RAZ, A RIGBY, PWJ RINI, JM WANG, JL TI GALECTINS - A FAMILY OF ANIMAL BETA-GALACTOSIDE-BINDING LECTINS SO CELL LA English DT Letter C1 UNIV LIEGE, B-4000 LIEGE, BELGIUM. UNIV OKLAHOMA, OKLAHOMA CITY, OK 73190 USA. COLUMBIA UNIV, NEW YORK, NY 10032 USA. CLIN RES CTR, HARROW HA1 3UJ, MIDDX, ENGLAND. TEIKYO UNIV, SAGAMIKO, KANAGAWA 19901, JAPAN. NATL INST MED RES, LONDON NW7 1AA, ENGLAND. SCRIPPS RES INST, LA JOLLA, CA 92037 USA. UNIV TEXAS, MD ANDERSON CANC CTR, HOUSTON, TX 77030 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. UNIV ORLEANS, CNRS, F-4507 ORLEANS 02, FRANCE. MASSACHUSETTS GEN HOSP, BOSTON, MA 02129 USA. INSERM, U257, F-75230 PARIS, FRANCE. MICHIGAN CANC FDN, DETROIT, MI 48201 USA. UNIV TORONTO, TORONTO M5S 1A8, ON, CANADA. MICHIGAN STATE UNIV, E LANSING, MI 48824 USA. RP BARONDES, SH (reprint author), UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. OI Leffler, Hakon/0000-0003-4482-8945 NR 3 TC 827 Z9 850 U1 3 U2 41 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD FEB 25 PY 1994 VL 76 IS 4 BP 597 EP 598 DI 10.1016/0092-8674(94)90498-7 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MZ285 UT WOS:A1994MZ28500003 PM 8124704 ER PT J AU BOGAN, JS PAGE, DC AF BOGAN, JS PAGE, DC TI OVARY - TESTIS - A MAMMALIAN DILEMMA SO CELL LA English DT Review ID DENYS-DRASH SYNDROME; SEX-DETERMINING REGION; TUMOR-SUPPRESSOR GENE; Y-CHROMOSOME; UROGENITAL DEVELOPMENT; XY-FEMALE; WT1 GENE; MOUSE; SRY; MICE C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02142. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. RP BOGAN, JS (reprint author), MIT,WHITEHEAD INST BIOMED RES,HOWARD HUGHES RES LABS,CAMBRIDGE,MA 02142, USA. RI Bogan, Jonathan/A-1575-2010 OI Bogan, Jonathan/0000-0001-6463-8466 NR 39 TC 45 Z9 46 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD FEB 25 PY 1994 VL 76 IS 4 BP 603 EP 607 DI 10.1016/0092-8674(94)90501-0 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MZ285 UT WOS:A1994MZ28500004 PM 8124705 ER PT J AU KOBAYASHI, T TAO, T GERGELY, J COLLINS, JH AF KOBAYASHI, T TAO, T GERGELY, J COLLINS, JH TI STRUCTURE OF THE TROPONIN COMPLEX - IMPLICATIONS OF PHOTOCROSS-LINKING OF TROPONIN-I TO TROPONIN-C THIOL MUTANTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RABBIT SKELETAL-MUSCLE; NUCLEAR-MAGNETIC-RESONANCE; CALCIUM-BINDING SITES; X-RAY-SCATTERING; INHIBITORY REGION; PROTEOLYTIC FRAGMENTS; REGULATORY DOMAIN; PEPTIDE COMPLEX; CROSS-LINKING; CALMODULIN AB Ca2+ regulation of vertebrate-striated muscle contraction is initiated by conformational changes in the Ca2+-binding protein troponin C (TnC) and subsequent changes in the interaction of TnC with the inhibitory protein TnI. We have constructed mutants of rabbit skeletal muscle TnC in which natural Cys-98 was replaced by Leu, and a single Cys residue was introduced at position 12 (TnC12) or 89 (TnC89). Cys residues of mutant TnCs were derivatized with 4-maleimidobenzophenone and photocross-linked to TnI in binary TnC.TnI complexes. After digestion with CNBr or proteases, crosslinked peptides were purified and sequenced. TnC12 cross-linked at or near TnI Met-134 in a region known to be sensitive not only to occupancy of the regulatory Ca2+-binding sites of TnC but also to the contractile state of the thin filament. TnC89 cross-linked to TnI(108-113) in the inhibitory region. Taken together with earlier findings, these results indicate that in the Tnc TnI complex, both domains of TnC, as well as the linker region between them, make contact with the inhibitory region of TnI. Our data also indicate that the N- and C-terminal domains of TnC interact with opposite ends of the TnI inhibitory region. C1 UNIV MARYLAND,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21201. UNIV MARYLAND,CTR MED BIOTECHNOL,INST BIOTECHNOL,BALTIMORE,MD 21201. BOSTON BIOMED RES INST,DEPT MUSCLE RES,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NHLBI NIH HHS [R37-HL05949]; NIAMS NIH HHS [AR-21673] NR 39 TC 56 Z9 56 U1 1 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 FEB 25 PY 1994 VL 269 IS 8 BP 5725 EP 5729 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MY840 UT WOS:A1994MY84000040 PM 8119911 ER PT J AU ERNST, TJ SLATTERY, KE GRIFFIN, JD AF ERNST, TJ SLATTERY, KE GRIFFIN, JD TI P210(BCR/ABL) AND P160(V-ABL) INDUCE AN INCREASE IN THE TYROSINE PHOSPHORYLATION OF P93(C-FES) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; FUJINAMI SARCOMA-VIRUS; V-ABL; C-FPS; PROTEIN-KINASE; CELL-LINE; ONCOGENE PRODUCTS; TRANSGENIC MICE; FES LOCUS; EXPRESSION AB Chronic myelogenous leukemia is caused by a reciprocal chromosomal translocation of human chromosomes 9 and 22. The resulting fusion protein, p210(Bcr/Abl), has enhanced tyrosine kinase activity compared with the normal cellular homologue, p145(c-Abl). Expression of this chimeric protein in hematopoietic cell lines results in a rapid progression to growth factor independence and increased tyrosine phosphorylation of a number of unidentified cellular proteins. In this study, we show that the phosphorylation state of the hematopoietically restricted tyrosine kinase, p93(c-Fes), is increased. Increased phosphorylation of p93(c-Fes) was detected in p210(Bcr/Abl)(+) human leukemic cell lines, in primary leukemic cells from patients with chronic myelogenous leukemia, and in myeloid cell lines expressing p210(Bcr/Abl) after transfection. Furthermore, p93(c-Fes) phosphorylation was increased by p210(Bcr/Abl) even when coexpressed in NIH 3T3 fibroblasts. v-abl expression was also found to increase the tyrosine phosphorylation of p93(c-Fes) This increased phosphorylation was found to be accompanied by an increase in the ability of p93(c-Fes) to phosphorylate exogenous substrates. p93(c-Fes) could contribute to the transforming activity of the abl oncogenes. RP ERNST, TJ (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] NR 48 TC 47 Z9 47 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 25 PY 1994 VL 269 IS 8 BP 5764 EP 5769 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MY840 UT WOS:A1994MY84000046 PM 8119916 ER PT J AU SHAW, SK CEPEK, KL MURPHY, EA RUSSELL, GJ BRENNER, MB PARKER, CM AF SHAW, SK CEPEK, KL MURPHY, EA RUSSELL, GJ BRENNER, MB PARKER, CM TI MOLECULAR-CLONING OF THE HUMAN MUCOSAL LYMPHOCYTE INTEGRIN ALPHA(E) SUBUNIT - UNUSUAL STRUCTURE AND RESTRICTED RNA DISTRIBUTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY HML-1; AMINO-ACID-SEQUENCE; HAIRY-CELL LEUKEMIA; LEUKOCYTE ADHESION GLYCOPROTEIN; MESSENGER-RNAS; INTESTINAL LYMPHOCYTES; BETA-7 SUBUNIT; CHEMICAL MODIFICATION; CLEAVAGE SITES; T-CELLS AB The human mucosal lymphocyte-1 (HML-1) antigen is expressed on a subclass of T-lymphocytes known as intra epithelial lymphocytes which are located between mucosal epithelial cells. The HML-1 complex is known to mediate adhesion of intra-epithelial T-lymphocytes to epithelial cell monolayers in vitro. We and others have shown that the HBL-1 antigen is an integrin composed of the beta(7) subunit in association with a novel alpha subunit, alpha(E). Here we report the cloning of the alpha(E) cDNA and its primary amino acid sequence. alpha(E) contained an inserted or I domain and was more homologous to the other I domain containing integrins than to the cleaved group of integrin alpha subunits. However, alpha(E) contained a unique extra domain of 55 amino acids located just NH2-terminal 60 the I domain without counterpart in other integrins. This extra domain contained a stretch of 18 consecutive charged residues and included a proteolytic cleavage site. Thus alpha(E) is the only I domain containing integrin a subunit that is also cleaved, and the cleavage site is distinct from that of members of the cleaved group of integrin alpha subunits. These structural features mark alpha(E) as an unusual member of the integrin family. High levels of alpha(E) and beta(7) mRNA were restricted to mucosal lymphocytes supporting the hypothesis that alpha(E) beta(7) plays a role in the localization or site-specific functions of intra-epithelial T-lymphocytes. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP SHAW, SK (reprint author), BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL IMMUNOL,DIV MED SCI,LYMPHOCYTE BIOL SECT,RM 507,SGMB,BOSTON,MA 02115, USA. FU NIAMS NIH HHS [AR 36308] NR 75 TC 98 Z9 99 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 FEB 25 PY 1994 VL 269 IS 8 BP 6016 EP 6025 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MY840 UT WOS:A1994MY84000082 PM 8119947 ER PT J AU WEISSMAN, NJ WEYMAN, AE AF WEISSMAN, NJ WEYMAN, AE TI CORONARY ATHERECTOMY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP WEISSMAN, NJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 1 U2 1 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 FEB 24 PY 1994 VL 330 IS 8 BP 539 EP 539 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MX436 UT WOS:A1994MX43600005 PM 8302320 ER PT J AU EMANUEL, EJ EMANUEL, LL AF EMANUEL, EJ EMANUEL, LL TI THE ECONOMICS OF DYING - THE ILLUSION OF COST SAVINGS AT THE END OF LIFE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CELL LUNG-CANCER; RANDOMIZED TRIAL; CRITICALLY ILL; MEDICAL-CARE; ADVANCE DIRECTIVES; NATIONAL HOSPICE; CHEMOTHERAPY; RESUSCITATION; EXPENDITURES; PREFERENCES C1 HARVARD UNIV,SCH MED,DIV MED ETH,BOSTON,MA. RP EMANUEL, EJ (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 59 TC 245 Z9 246 U1 3 U2 7 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 FEB 24 PY 1994 VL 330 IS 8 BP 540 EP 544 DI 10.1056/NEJM199402243300806 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MX436 UT WOS:A1994MX43600006 PM 8302321 ER PT J AU SHIPP, MA HARRINGTON, DP AF SHIPP, MA HARRINGTON, DP TI A PREDICTIVE MODEL FOR NON-HODGKINS-LYMPHOMA - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP SHIPP, MA (reprint author), DANA FARBER CANC INST,BOSTON,MA 02115, 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 FEB 24 PY 1994 VL 330 IS 8 BP 574 EP 575 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MX436 UT WOS:A1994MX43600023 ER PT J AU JELLINEK, M NURCOMBE, B AF JELLINEK, M NURCOMBE, B TI MANAGED CARE, MENTAL-HEALTH, AND THE MARKETPLACE - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 VANDERBILT UNIV,SCH MED,NASHVILLE,TN. RP JELLINEK, M (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 23 PY 1994 VL 271 IS 8 BP 588 EP 588 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MW477 UT WOS:A1994MW47700020 ER PT J AU MASZCZYNSKA, I MIKASZEWSKA, M KOSSON, D CARR, DB SZYFELBEIN, SK LIPKOWSKI, AW AF MASZCZYNSKA, I MIKASZEWSKA, M KOSSON, D CARR, DB SZYFELBEIN, SK LIPKOWSKI, AW TI INTERACTION BETWEEN MORPHINE AND OPIOID-PEPTIDES AFTER SC ADMINISTRATION SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT 24th International Narcotics Research Conference (INRC): Towards a Molecular Basis in Opioid Research CY JUL 10-15, 1993 CL SKOVDE, SWEDEN AB It is possible that peripheral analgesic targets may enhance central analgesia. We present our preliminary results of selected opioid peptides on morphine (MOR) analgesia. Coinjection of dermorphin with MOR resulted in antinociceptive synergy, whereas morphiceptin coinjected with MOR yielded antinociceptive activity lower than MOR alone. At lower doses of MOR, DADLE strongly potentiates analgesia, but at higher doses of MOR, DADLE inhibits the antinociceptive effect of MOR. C1 MED ACAD WARSAW,DEPT ANESTHESIOL & INTENS CARE,PL-02005 WARSAW,POLAND. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. RP MASZCZYNSKA, I (reprint author), POLISH ACAD SCI,MED RES CTR,PL-00784 WARSAW,POLAND. NR 1 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD FEB 21 PY 1994 SU 1 BP S243 EP S244 PG 2 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA NA245 UT WOS:A1994NA24500121 ER PT J AU HIRAIZUMI, S SPOHR, U SPIRO, RG AF HIRAIZUMI, S SPOHR, U SPIRO, RG TI LIGAND AFFINITY CHROMATOGRAPHIC PURIFICATION OF RAT-LIVER GOLGI ENDOMANNOSIDASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ALPHA-D-MANNOSIDASE; N-LINKED OLIGOSACCHARIDES; GLUCOSIDASE-II-DEFICIENT; PATHWAY; CELLS; GLYCOPROTEINS; MEMBRANES; PROTEINS AB In order to achieve isolation of endo-alpha-D-mannosidase, a GoIgi-located processing enzyme that accomplishes deglucosylation of glycoproteins with N-linked carbohydrate units by cleaving the linkage between the glucose-substituted mannose residue and the remainder of the oligosaccharide, we have prepared an affinity matrix (Glc alpha 1-->3Man-O-(CH2)8CONH-Affi-Gel 102) containing the derivative of the characteristic disaccharide product of this enzyme. Chromatography of a Triton extract of rat liver Golgi membranes on a column of this gel in the presence of castanospermine to prevent binding of alpha-glucosidases permitted a rapid purification of the endomannosidase (70,000-fold over the homogenate) with a 12% yield. This purified enzyme was free of other processing glycosidases and was completely inhibited by Glc alpha 1-->3(1-deoxy)mannojirimycin. Examination of the endomannosidase by SDS-polyacrylamide gel electrophoresis revealed a doublet (M(r) 60,000 and 56,000) with the bands being of approximately equal density. Gel permeation high performance liquid chromatography indicated that in its native form the enzyme has an oligomeric structure (M(r) similar to 560,000) consisting of eight to ten subunits. C1 JOSLIN DIABET CTR,ELLIOTT P JOSLIN RES LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV ALBERTA,DEPT CHEM,EDMONTON T6G 2G2,AB,CANADA. CHEMBIOMED LTD,EDMONTON T6G 2G2,AB,CANADA. FU NIDDK NIH HHS [DK 17477] NR 22 TC 17 Z9 18 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 FEB 18 PY 1994 VL 269 IS 7 BP 4697 EP 4700 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MX571 UT WOS:A1994MX57100002 PM 8106437 ER PT J AU HALLAK, H MUSZBEK, L LAPOSATA, M BELMONTE, E BRASS, LF MANNING, DR AF HALLAK, H MUSZBEK, L LAPOSATA, M BELMONTE, E BRASS, LF MANNING, DR TI COVALENT BINDING OF ARACHIDONATE TO G-PROTEIN ALPHA-SUBUNITS OF HUMAN PLATELETS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID FATTY-ACIDS; MYRISTOYLATION; MEMBRANE; ACYLATION; PALMITOYLATION; AFFINITY; THROMBIN; RELEASE; CELLS AB The alpha subunits of GTP-binding regulatory proteins (G proteins) are subject to lipid modifications required for anchorage to membrane and/or interactions with other proteins, With the knowledge that alpha subunits are palmitoylated, which we demonstrate here for human platelets, we sought to determine whether these subunits also bind arachidonate and myristate in a covalent, post-translational manner. All alpha subunits examined were found to incorporate radioactivity upon incubation of human platelets with [H-3]palmitate, [H-3]arachidonate, and [H-3]myristate. The identity of [H-3]palmitate and [H-3]arachidonate as covalently bound fatty acids was confirmed by high pressure liquid chromatography following alkaline methanolysis. With [H-3]myristate, however, the bound fatty acid proved to be [H-3]palmitate, presumably generated by a 2-carbon chain elongation. Protein-bound [H-3]palmitate and [H-3]arachidonate were released by hydroxylamine at neutral pH, implying a thioester linkage between protein and fatty acid. Thus, post-translational modifications of G protein alpha subunits include palmitoylation and arachidonoylation, but not myristoylation, Given the different physical properties of saturated and unsaturated fatty acids and the large-scale release of arachidonate during platelet activation, changes in arachidonate incorporation may serve as an important regulator of a subunit function. C1 UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT MED & PATHOL,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV MED SCH DEBRECEN,DEPT CLIN CHEM,H-4012 DEBRECEN,HUNGARY. FU NHLBI NIH HHS [HL45181]; NIGMS NIH HHS [GM34781]; NIMH NIH HHS [MH14654] NR 31 TC 92 Z9 92 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 FEB 18 PY 1994 VL 269 IS 7 BP 4713 EP 4716 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MX571 UT WOS:A1994MX57100006 PM 8106438 ER PT J AU MATSUGUCHI, T SALGIA, R HALLEK, M EDER, M DRUKER, B ERNST, TJ GRIFFIN, JD AF MATSUGUCHI, T SALGIA, R HALLEK, M EDER, M DRUKER, B ERNST, TJ GRIFFIN, JD TI SHC PHOSPHORYLATION IN MYELOID CELLS IS REGULATED BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, INTERLEUKIN-3, AND STEEL FACTOR AND IS CONSTITUTIVELY INCREASED BY P210(BCR/ABL) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; RECEPTOR GENE FAMILY; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; HEMATOPOIETIC-CELLS; PHILADELPHIA-CHROMOSOME; EXPRESSION CLONING; GM-CSF; PROTEINS; ACTIVATION AB Granulocyte macrophage colony-stimulating factor, interleukin-3, and steel factor induce proliferation of hematopoietic cells through binding to specific, high affinity, cell surface receptors. However, little is known about post-receptor signal transduction pathways. Here we report that an SH2 domain containing protein previously implicated in the activation of p21(ras), Shc, is transiently tyrosine phosphorylated in myeloid cells after stimulation with granulocyte macrophage colony-stimulating factor, interleukin-3, or steel factor. Also, Shc was found to be constitutively tyrosine phosphorylated in myeloid cell Lines made factor independent by expression of p210(BCR/ABL). A Shc-associated 140-kDa protein was identified, which was phosphorylated on tyrosine residues transiently after cytokine stimulation and constitutively after expression of p210(BCR/ABL). These findings suggest that She could play an important role in a signal transduction pathway, which leads to the proliferation of myeloid cells. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MOLEC & CELLULAR BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA 34183, CA 36167] NR 46 TC 165 Z9 166 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 FEB 18 PY 1994 VL 269 IS 7 BP 5016 EP 5021 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MX571 UT WOS:A1994MX57100051 PM 7508932 ER PT J AU DRUKER, BJ NEUMANN, M OKUDA, K FRANZA, BR GRIFFIN, JD AF DRUKER, BJ NEUMANN, M OKUDA, K FRANZA, BR GRIFFIN, JD TI REL IS RAPIDLY TYROSINE-PHOSPHORYLATED FOLLOWING GRANULOCYTE-COLONY-STIMULATING FACTOR TREATMENT OF HUMAN NEUTROPHILS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; DNA-BINDING SUBUNIT; VIRUS STRAIN-T; C-REL; SIGNAL TRANSDUCTION; FACTOR RECEPTOR; PROTO-ONCOGENE; PROTEINS; DORSAL; DROSOPHILA AB Stimulation of neutrophils with granulocyte-colony stimulating factor (G-CSF) results in an enhanced respiratory burst, prolonged survival, and increased tumor cell killing. The effects of G-CSF are mediated by binding to specific, high affinity receptors. G-CSF receptors lack intrinsic tyrosine kinase activity, but activation of the receptor results in the rapid induction of tyrosine kinase activity. Antiphosphotyrosine immunoblots of whole cell lysates prepared from neutrophils show that the G-CSF rapidly induces prominent tyrosine phos phosphorylation of a protein of a relative molecular mass of 80 kDa. Using monospecific antibodies, the 80-kDa tyrosine-phosphorylated protein has been shown to be p80(c-rel), a proto-oncogene belonging to a family of transcriptional regulators which include NF-kB. The induction of tyrosine phosphorylation of p80(c-rel) was unique to G-CSF in that granulocyte-macrophage colony stimulating factor which also stimulates neutrophils and induces tyrosine phosphorylation does not result in tyro sine phosphorylation of p80(c-rel). The consequences of p80(c-rel) tyrosine phosphorylation are not yet known; however, tyrosine-phosphorylated p80(c-rel) is capable of binding to DNA, and G-CSF stimulation results in an increase in the amount of p80(c-rel) which binds to DNA, These results demonstrate that one of the first biochemical events which occurs in neutrophils following G-CSF stimulation, activation of a tyrosine kinase, leads directly to the tyrosine phosphorylation of p80(c-rel). Thus, the tyrosine kinase activated by G-CSF appears to directly transduce a signal to a protein which functions as a transcriptional regulator. C1 DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. COLD SPRING HARBOR LAB,FREEMAN LAB CANC CELL BIOL,COLD SPRING HARBOR,NY 11724. FU NCI NIH HHS [CA34183, CA01422, CA36167] NR 29 TC 43 Z9 43 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 FEB 18 PY 1994 VL 269 IS 7 BP 5387 EP 5390 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MX571 UT WOS:A1994MX57100103 PM 7508937 ER PT J AU FUSTER, V AF FUSTER, V TI THROMBOLYTIC THERAPY FOR ACUTE MYOCARDIAL-INFARCTION - GUSTO CRITICIZED SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP FUSTER, V (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 5 TC 0 Z9 0 U1 0 U2 1 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 FEB 17 PY 1994 VL 330 IS 7 BP 506 EP 506 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MW480 UT WOS:A1994MW48000022 ER PT J AU BUSSEY, HI LINN, WD AF BUSSEY, HI LINN, WD TI WARFARIN AND ASPIRIN AFTER HEART-VALVE REPLACEMENT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 AUDIE MURPHY VET AFFAIRS MED CTR,SAN ANTONIO,TX 78284. RP BUSSEY, HI (reprint author), UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284, USA. NR 0 TC 2 Z9 2 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 FEB 17 PY 1994 VL 330 IS 7 BP 508 EP 508 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MW480 UT WOS:A1994MW48000026 PM 8289865 ER PT J AU MULROW, CD GERETY, MB KANTEN, D CORNELL, JE DENINO, LA CHIODO, L AGUILAR, C ONEIL, MB ROSENBERG, J SOLIS, RM AF MULROW, CD GERETY, MB KANTEN, D CORNELL, JE DENINO, LA CHIODO, L AGUILAR, C ONEIL, MB ROSENBERG, J SOLIS, RM TI A RANDOMIZED TRIAL OF PHYSICAL REHABILITATION FOR VERY FRAIL NURSING-HOME RESIDENTS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RESOURCE UTILIZATION GROUPS; LONG-TERM CARE; IMPACT; MUSCLE; EFFICACY; THERAPY; UNIT AB Background.-Past studies suggest multidisciplinary interventions that include physical therapy (PT) can improve function of nursing home residents. This trial specifically evaluates effects of PT for frail long-stay nursing home residents. Design.-Randomized, controlled trial. Setting.-One academic nursing home and eight community nursing homes. Patients.-A total of 194 elderly nursing home residents dependent in at least two activities of daily living residing in the nursing home for at least 3 months. Interventions.-Patients were randomized to individually tailored one-on-one PT sessions or friendly visits (FVs) three times a week for 4 months. Physical therapy included range-of-motion, strength, balance, transfer, and mobility exercises. Main Outcome Measures.-Performance-based physical function assessed by the Physical Disability Index; self-perceived health status assessed with the Sickness Impact Profile; observer-reported activities of daily living; and falls. Results.-Eighty-nine percent and 92% of PT and FV sessions, respectively, were attended; 5% and 9% of subjects dropped out in the PT group and FV group, respectively. Compared with the FV group, the PT group experienced no significant improvements in overall Physical Disability Index, Sickness Impact Profile, or activities of daily living scores. A 15.5% improvement in the mobility subscale of the Physical Disability Index was seen (95% confidence interval [CI], 6.4% to 24.7%); no benefits in range-of-motion, strength, or balance subscales were found. Compared with the FV group, the PT group used assistive devices for bed mobility tasks less often (P=.06) and were less likely to use assistive devices and wheelchairs for locomotion (P<.005). There were 79 falls in the PT group vs 60 falls in the FV group (P=.11). Charge for the 4-month PT program was $1220 per subject (95% CI, $412 to $1832). Conclusion.-This standardized physical therapy program provided modest mobility benefits for very frail long-stay nursing home residents with physical disability due to multiple comorbid conditions. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. RP MULROW, CD (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,2400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [UO1AG09117] NR 41 TC 176 Z9 176 U1 9 U2 18 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 16 PY 1994 VL 271 IS 7 BP 519 EP 524 DI 10.1001/jama.271.7.519 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA MV423 UT WOS:A1994MV42300034 PM 8301766 ER PT J AU ESKEY, CJ WOLMARK, N MCDOWELL, CL DOMACH, MM JAIN, RK AF ESKEY, CJ WOLMARK, N MCDOWELL, CL DOMACH, MM JAIN, RK TI RESIDENCE TIME DISTRIBUTIONS OF VARIOUS TRACERS IN TUMORS - IMPLICATIONS FOR DRUG-DELIVERY AND BLOOD-FLOW MEASUREMENT SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SOLID TUMORS; TRANSPORT; CARCINOMA; PRESSURE AB Background: The evaluation of rates of tumor blood now with small, rapidly diffusing tracers requires an accurate model for mass transport within the tissue and tracer biodistribution. It is generally assumed that the whole tumor or several tumor regions act as well-mixed compartments, an assumption that has never been evaluated in tumors. Purpose: The purpose of this study was to assess the accuracy of compartmental flow models in tissue-isolated tumors. Methods: We measured the residence time distributions of various tracers with the use of ex vivo perfusion of tissue-isolated rat R3230AC mammary tumors. This approach permits simultaneous, independent measurements of total blood flow and tracer concentrations in afferent and efferent vessels. The isolated tumors were perfused with Krebs-Henseleit solution, to which could be added D2O saline and either 3% by volume F44-E (a perfluorocarbon emulsion) or 1% by weight fluorescein isothiocyanate (FITC)-albumin. A pulse of D2O and one of the other tracers was added to the perfusing liquid, and the relative concentrations of both D2O and perfluorocarbon or FITC-albumin were measured in the tumor effluent. D2O and the perfluorocarbon were measured with an imaging spectrometer tuned to either H-2 or F-19. FITC-albumin concentrations were measured by luminescence spectrometry. The results were analyzed using various compartmental models. Results: The tracer residence time distribution deviated from that expected for a single well-mixed compartment. Only half of the D2O left the tumor with a time constant consistent with the known perfusate flow. The remainder exited the tumor more rapidly than expected, and neither vascular shunting nor macroscopic flow heterogeneity accounts for this component of the D2O flow. However, two-compartment models provide an improved fit to the data. Conclusions: Our experiments demonstrate that the simple compartmental model used to estimate blood flow with diffusible tracers is not accurate. Implications: The nonideal blood flow found in our experiments reflects phenomena that may have important effects in the development of pharmacokinetic models of drug delivery to tumors. The accuracy of blood flow measurements, made with such techniques as nuclear magnetic resonance, positron-emission tomography, and computed tomography, may also be affected when they rely on the assumption that the tumor is a collection of well-mixed compartments. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114. CARNEGIE MELLON UNIV,DEPT CHEM ENGN,PITTSBURGH,PA 15213. UNIV PITTSBURGH,DEPT SURG,PITTSBURGH,PA 15260. FU NCI NIH HHS [CA56591]; NCRR NIH HHS [RR-03631] NR 28 TC 33 Z9 34 U1 0 U2 2 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 FEB 16 PY 1994 VL 86 IS 4 BP 293 EP 299 DI 10.1093/jnci/86.4.293 PG 7 WC Oncology SC Oncology GA MV706 UT WOS:A1994MV70600015 PM 8158684 ER PT J AU RIGOTTI, NA MCKOOL, KM SHIFFMAN, S AF RIGOTTI, NA MCKOOL, KM SHIFFMAN, S TI PREDICTORS OF SMOKING CESSATION AFTER CORONARY-ARTERY BYPASS GRAFT-SURGERY - RESULTS OF A RANDOMIZED TRIAL WITH 5-YEAR FOLLOW-UP SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE SMOKING CESSATION; CORONARY ARTERY BYPASS; OUTCOME AND PROCESS ASSESSMENT (HEALTH CARE); BEHAVIOR THERAPY; CORONARY DISEASE ID RISK-FACTORS; MYOCARDIAL-INFARCTION; CIGARETTE-SMOKING; DISEASE; CASS; INTERVENTION; MORBIDITY; SURVIVAL; SEVERITY; THERAPY AB Objective: To test the efficacy of a smoking cessation program for inpatients recovering from coronary artery bypass graft surgery and to identify predictors of cessation. Design: Randomized, controlled clinical trial. Setting: Postoperative cardiac surgery unit of a large teaching hospital. Patients: Patients scheduled for coronary artery bypass surgery by participating surgeons between 1 July 1986 and 1 July 1987 who had smoked 1 or more packs of cigarettes in the 6 months before admission. Of 120 eligible patients, 93 enrolled and 87 were discharged alive. All survivors were followed for at least 1 year; 94% were followed for a median of 5.5 years. Intervention: A three-session, nurse-delivered behavior modification program using a videotape and face-to-face counseling was compared to usual care. Measurements: Smoking status was assessed six times in the year after surgery and 5.5 years after surgery. Self-reported nonsmoking was validated by saliva cotinine assay 1 and 5.5 years after surgery. Results: No statistically significant differences were found between control (n = 43) and intervention (n = 44) groups at baseline. One and 5.5 years after hospital discharge, validated continuous nonsmoking rates were identical in intervention and control groups (51% at 1 year; 44% at 5.5 years). Multiple logistic regression identified four factors that were independently associated with nonsmoking for 1 year: fewer than 3 previous attempts to quit (odds ratio, 7.4; 95% Cl, 1.9 to 29.1); more than 1 week of preoperative nonsmoking (odds ratio, 10.0; Cl, 2.0 to 50.2); definite intention to quit smoking (odds ratio, 12.0; Cl, 2.6 to 55.1); and no difficulty not smoking in the hospital (odds ratio, 9.6; Cl, 1.8 to 52.2). Nonsmoking for 5.5 years was independently associated with two of these factors: fewer than three previous attempts to quit and intention to quit smoking after surgery. Cessation was not related to demographic factors, daily cigarette consumption, disease severity, hospital course, social support, or beliefs and attitudes. Conclusions: Even without specific intervention, nearly one half of smokers quit for 5 years after coronary artery bypass surgery. A short inpatient education program did not increase this rate. Future efforts should target the time after discharge and focus on increasing motivation in patients who have repeatedly failed to quit. C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. HARVARD UNIV,INST STUDY SMOKING BEHAV & POLICY,BOSTON,MA. RI Shiffman, Saul/K-7337-2012 FU NCI NIH HHS [CA01673-01] NR 33 TC 110 Z9 111 U1 0 U2 2 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 FEB 15 PY 1994 VL 120 IS 4 BP 287 EP 293 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MW103 UT WOS:A1994MW10300005 PM 8291821 ER PT J AU KASINATH, BS BLOCK, JA SINGH, AK TERHUNE, WC MALDONADO, R DAVALATH, S KALLGREN, MJ WANNA, L AF KASINATH, BS BLOCK, JA SINGH, AK TERHUNE, WC MALDONADO, R DAVALATH, S KALLGREN, MJ WANNA, L TI REGULATION OF RAT GLOMERULAR EPITHELIAL-CELL PROTEOGLYCANS BY HIGH-GLUCOSE MEDIUM SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; BASEMENT-MEMBRANE GLYCOSAMINOGLYCANS; INDUCED DIABETIC RATS; GROWTH-FACTOR-BETA; INCREASED PERMEABILITY; MESANGIAL CELLS; COMPLICATIONS; CULTURE; TISSUE; HEPARAN-(SO4)-S-35 AB In diabetic nephropathy the heparan sulfate proteoglycan (HSPG) content of the glomerular basement membrane (GBM) is reduced but the cellular mechanisms involved have not been studied. Glomerular epithelial cells (GEC) are thought to be the source of HSPG present in the GBM. In this study we examined if proteoglycan metabolism of the rat GEC in culture is dysregulated in a metabolic environment simulating diabetes. Following incubation for 8 days with a serum-supplemented medium containing 30 mM glucose and no added insulin, a significant increase in the overall synthesis of (SO4)-S-35-labeled molecules by the GEC was seen compared to control monolayers incubated with medium containing 5 mM glucose and insulin. Ion exchange chromatography revealed that 30 mM glucose did not alter the anionic charge density of proteoglycans, but significantly increased the amount of S-35-labeled low-anionic macromolecules in the medium; mannitol induced similar changes. Sepharose CL-4B chromatography, glycosaminoglycan analysis and immunoprecipitation of control cell layer proteoglycans demonstrated the presence of HSPG of hydrodynamic size, K-av 0.4, resembling rat GBM HSPG in size and antigenic nature. Incubation of GEC with 30 mM glucose resulted in a significant reduction (58%) in this HSPG species, an effect not seen with equimolar mannitol. Additionally, 30 mM glucose induced a significant increment in synthesis of a small HS species (K-av 0.71 on Sepharose CL-4B column) present in the cell layer. Our findings suggest that both osmotic and nonosmotic mechanisms are operative in dysregulation of glycopeptide metabolism by high-glucose medium and that reduced synthesis by the GEC may contribute to decreased content of GBM HSPG in diabetic nephropathy. (C) 1994 Academic Press, Inc. C1 RUSH MED COLL,CHICAGO,IL. LOYOLA UNIV,SCH MED,CHICAGO,IL. RP KASINATH, BS (reprint author), UNIV TEXAS,AUDIE L MURPHY MEM VET ADM HOSP,HLTH SCI CTR,DEPT MED,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDDK NIH HHS [DK 41517] NR 47 TC 12 Z9 12 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD FEB 15 PY 1994 VL 309 IS 1 BP 149 EP 159 DI 10.1006/abbi.1994.1097 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MY517 UT WOS:A1994MY51700023 PM 8117103 ER PT J AU SAVAGE, CR WEILBURG, JB DUFFY, FH BAER, L SHERA, DM JENIKE, MA AF SAVAGE, CR WEILBURG, JB DUFFY, FH BAER, L SHERA, DM JENIKE, MA TI LOW-LEVEL SENSORY PROCESSING IN OBSESSIVE-COMPULSIVE DISORDER - AN EVOKED-POTENTIAL STUDY SO BIOLOGICAL PSYCHIATRY LA English DT Article DE OBSESSIVE-COMPULSIVE DISORDER; VISUAL EVOKED POTENTIALS; AUDITORY EVOKED POTENTIALS; SENSORY PROCESSING ID AUDITORY-CORTEX; COMPONENTS; GENERATORS; LESIONS; SCALP; LOBE; AEP AB This study used visual and auditory evoked potentials (VEP and AEP) to study low-level sensory processing in a group of 15 unmedicated subjects with obsessive-compulsive disorder (OCD) and 30 age-matched, gender-matched, and handedness-matched normal controls. EPs were recorded to flash (VEP) and binaural click (AEP) stimulation. OCD subjects were found to have significantly shorter latencies on NI and P2 of the AEP, and no differences were found in the VEP. Results indicate abnormal information processing states in OCD during low-level auditory processing, but not during low-level visual processing. Neural generators of the VEP and AEP are briefly reviewed and results are discussed in relation to current neurobiological models of OCD. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. NR 23 TC 22 Z9 22 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 15 PY 1994 VL 35 IS 4 BP 247 EP 252 DI 10.1016/0006-3223(94)91255-6 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NA789 UT WOS:A1994NA78900004 PM 8186329 ER PT J AU SCHLOSSMAN, SF BOUMSELL, L GILKS, W HARLAN, JM KISHIMOTO, T MORIMOTO, C RITZ, J SHAW, S SILVERSTEIN, RL SPRINGER, TA TEDDER, TF TODD, RF AF SCHLOSSMAN, SF BOUMSELL, L GILKS, W HARLAN, JM KISHIMOTO, T MORIMOTO, C RITZ, J SHAW, S SILVERSTEIN, RL SPRINGER, TA TEDDER, TF TODD, RF TI CD ANTIGENS 1993 SO BLOOD LA English DT Editorial Material RP SCHLOSSMAN, SF (reprint author), DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 NR 1 TC 23 Z9 23 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 FEB 15 PY 1994 VL 83 IS 4 BP 879 EP 880 PG 2 WC Hematology SC Hematology GA MW692 UT WOS:A1994MW69200001 PM 8111060 ER PT J AU TOMITA, Y SACHS, DH SYKES, M AF TOMITA, Y SACHS, DH SYKES, M TI MYELOSUPPRESSIVE CONDITIONING IS REQUIRED TO ACHIEVE ENGRAFTMENT OF PLURIPOTENT STEM-CELLS CONTAINED IN MODERATE DOSES OF SYNGENEIC BONE-MARROW SO BLOOD LA English DT Article ID MIXED ALLOGENEIC CHIMERAS; NONLETHAL PREPARATIVE REGIMEN; VS-HOST DISEASE; LYMPHOID-CELLS; TOLERANCE; MICE; TRANSPLANTATION; RECIPIENTS; SUPPRESSION; ALLOGRAFTS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,SURG SERV,BOSTON,MA 02129. FU NCI NIH HHS [R01 CA55290]; NHLBI NIH HHS [R01 HL49915] NR 34 TC 127 Z9 128 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 FEB 15 PY 1994 VL 83 IS 4 BP 939 EP 948 PG 10 WC Hematology SC Hematology GA MW692 UT WOS:A1994MW69200010 PM 7906567 ER PT J AU KINASHI, T SPRINGER, TA AF KINASHI, T SPRINGER, TA TI STEEL FACTOR AND C-KIT REGULATE CELL-MATRIX ADHESION SO BLOOD LA English DT Article ID MOUSE AGGREGATION CHIMERAS; TYROSINE KINASE RECEPTOR; GROWTH-FACTOR; MAST-CELLS; PROTO-ONCOGENE; SI-LOCUS; W-LOCUS; MOLECULAR-CLONING; MUTANT MICE; CDNA CLONE C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [DK45104] NR 42 TC 162 Z9 164 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 FEB 15 PY 1994 VL 83 IS 4 BP 1033 EP 1038 PG 6 WC Hematology SC Hematology GA MW692 UT WOS:A1994MW69200020 PM 7509207 ER PT J AU GARABEDIAN, HD GOLD, HK NEWELL, JB COLLEN, D HAGSTROM, JN BOVILL, EG AF GARABEDIAN, HD GOLD, HK NEWELL, JB COLLEN, D HAGSTROM, JN BOVILL, EG TI ACCELERATED THROMBIN GENERATION DURING ANTICOAGULATION IN PATIENTS WITH UNSTABLE ANGINA-PECTORIS SO BLOOD LA English DT Letter ID HEPARIN C1 UNIV VERMONT,COLL MED,DEPT PATHOL,BURLINGTON,VT 05405. RP GARABEDIAN, HD (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 6 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 0006-4971 J9 BLOOD JI Blood PD FEB 15 PY 1994 VL 83 IS 4 BP 1155 EP 1155 PG 1 WC Hematology SC Hematology GA MW692 UT WOS:A1994MW69200036 PM 8111056 ER PT J AU LYNCH, TJ KALISH, LA KASS, F STRAUSS, G ELIAS, A SKARIN, A SHULMAN, L SUGARBAKER, D FREI, E AF LYNCH, TJ KALISH, LA KASS, F STRAUSS, G ELIAS, A SKARIN, A SHULMAN, L SUGARBAKER, D FREI, E TI CONTINUOUS-INFUSION CISPLATIN, 5-FLUOROURACIL, AND LEUCOVORIN FOR ADVANCED NONSMALL CELL LUNG-CANCER SO CANCER LA English DT Article DE NONSMALL CELL LUNG CANCER; CISPLATIN; 5-FLUOROURACIL; LEUCOVORIN; CLINICAL TRIAL; HUMAN SUBJECTS ID RANDOMIZED TRIAL; CHEMOTHERAPY; CARCINOMA; RADIOTHERAPY; MITOMYCIN; BOLUS AB Background. Cisplatin, 5-fluorouracil, and leucovorin (PFL) have demonstrated synergistic activity in preclinical models. Continuous infusion of these agents maximizes the potential for synergistic interaction and forms the basis of the PFL regimen. Methods. Sixty-one patients with advanced (Stages IIIB and IV) non-small cell lung cancer were entered into the study. Thirty-one were treated with cisplatin 25 mg/m(2)/day on days 1-5, 5-fluorouracil 800 mg/m(2)/day on days 2-6, and calcium leucovorin 500 mg/m(2)/day on days 1-6. Because of severe mucositis, the final 30 patients were treated with the same dosage of cisplatin but with the deletion on day 6 of leucovorin and B-fluorouracil. Cycles were repeated every 28 days. Response was assessed after two cycles. Responding patients received an additional two cycles. Patients with Stage IIIB disease received radiation therapy to the mediastinum and sites of involved disease. Results. PFL had an overall response rate of 41%. Median survival was 8.1 months, and median time to treatment failure was 4.2 months. Importantly, 68% (17 of 25) of responses were maximal after just two cycles of chemotherapy. Notable toxicities included mucositis (43% greater than or equal to Grade 3) and myelosuppression. Response, time to failure, or survival did not differ between the two schedules. Mucositis was less severe with 4-day PFL. Conclusions. PFL as given in this manner is an active regimen for the treatment of patients with advanced nonsmall cell lung cancer. The rapidity of response makes it a regimen for incorporation into protocols for Stage IIIA disease. A neoadjuvant study using PFL is underway. C1 DANA FABER CANC INST,DIV CLIN ONCOL,BOSTON,MA. DANA FABER CANC INST,DIV BIOSTAT,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV THORAC SURG,BOSTON,MA 02115. FU NCI NIH HHS [CA-19589, CA-06516] NR 23 TC 12 Z9 12 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 FEB 15 PY 1994 VL 73 IS 4 BP 1171 EP 1176 DI 10.1002/1097-0142(19940215)73:4<1171::AID-CNCR2820730408>3.0.CO;2-L PG 6 WC Oncology SC Oncology GA MY538 UT WOS:A1994MY53800007 PM 8313319 ER PT J AU GOLD, EB LEVITON, A LOPEZ, R AUSTIN, DF GILLES, FH HEDLEYWHYTE, ET KOLONEL, LN LYON, JL SWANSON, GM WEISS, NS WEST, DW ASCHENBRENER, C AF GOLD, EB LEVITON, A LOPEZ, R AUSTIN, DF GILLES, FH HEDLEYWHYTE, ET KOLONEL, LN LYON, JL SWANSON, GM WEISS, NS WEST, DW ASCHENBRENER, C TI THE ROLE OF FAMILY HISTORY IN RISK OF CHILDHOOD BRAIN-TUMORS SO CANCER LA English DT Article DE BRAIN TUMORS; CHILDREN; EPIDEMIOLOGY; FAMILIAL; RISK FACTORS ID CANCER; CHILDREN; EXPOSURE; OCCUPATION; NEOPLASMS; FIELDS; TWINS AB Background. Although brain tumors are the second most frequent malignancy in children, relatively little is known about the role of family history in risk of these tumors. Methods. Children under the age of 18 years (n = 361) in whom primary brain tumors were diagnosed were identified from eight United States population-based Surveillance, Epidemiology, and End Results registries and compared to matched controls (n = 1083) identified by random-digit dialing. Information regarding family history of birth defects or tumors was obtained, along with data on other potential risk factors, from interviews with the mothers and fathers of the index children. Results. No significant differences were found in family history of epilepsy. However, moderate elevations in risk were observed for a history of birth defects in maternal relatives, particularly for female propositi. Significantly more mothers (odds ratio [OR] = 1.63, 95% confidence limits [CL] = 1.03, 2.57) and maternal female relatives (OR = 2.15, 95% CL = 1.14, 4.06) of cases than of controls were reported to have had birth defects. History of birth defects in maternal relatives was particularly associated with childhood brain tumors of ''other'' (not astrocytoma or medulloblastoma) histologic type (OR = 2.37, 95% CL = 1.25, 4.53) and infratentorial tumors (OR = 1.76, 95% CL = 1.06, 2.93). Slight excesses of tumors were observed in paternal relatives of children with astrocytomas (OR = 1.43, 95% CL 0.93, 2.20) or with infratentorial tumors (OR = 1.46, 95% CL 0.97, 2.20). Risk of childhood brain tumors did not increase with the number of relatives affected with brain tumors, breast cancer, leukemia or lymphoma, soft tissue sarcomas, or all of these tumor types combined (the Li-Fraumeni syndrome). Conclusions. These findings suggest a modest increase in risk of childhood brain tumors associated with maternal family history of birth defects. Family history of tumors does not appear to contribute appreciably to an increased risk of brain tumors in children. C1 CHILDRENS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02114. CALIF DEPT HLTH SERV,EMERYVILLE,CA. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA 90027. UNIV SO CALIF,LOS ANGELES,CA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CANC RES CTR HAWAII,HONOLULU,HI 96813. UNIV UTAH,SALT LAKE CITY,UT. MICHIGAN STATE UNIV,E LANSING,MI 48824. UNIV WASHINGTON,SEATTLE,WA 98195. NO CALIF CANC CTR,UNION CITY,CA. NEBRASKA MED CTR,OMAHA,NE. RP GOLD, EB (reprint author), UNIV CALIF DAVIS,INST TOXICOL & ENVIRONM HLTH,DIV OCCUPAT & ENVIRONM MED & EPIDEMIOL,DAVIS,CA 95616, USA. FU NCI NIH HHS [CA21919, CA50371] NR 34 TC 20 Z9 20 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 1994 VL 73 IS 4 BP 1302 EP 1311 DI 10.1002/1097-0142(19940215)73:4<1302::AID-CNCR2820730428>3.0.CO;2-H PG 10 WC Oncology SC Oncology GA MY538 UT WOS:A1994MY53800027 PM 8313335 ER PT J AU BIANCHI, E COHEN, RL THOR, AT TODD, RF MIZUKAMI, IF LAWRENCE, DA LJUNG, BM SHUMAN, MA SMITH, HS AF BIANCHI, E COHEN, RL THOR, AT TODD, RF MIZUKAMI, IF LAWRENCE, DA LJUNG, BM SHUMAN, MA SMITH, HS TI THE UROKINASE RECEPTOR IS EXPRESSED IN INVASIVE BREAST-CANCER BUT NOT IN NORMAL BREAST-TISSUE SO CANCER RESEARCH LA English DT Note ID HUMAN MONONUCLEAR PHAGOCYTES; HUMAN-ENDOTHELIAL-CELLS; HUMAN-TUMOR-CELLS; PLASMINOGEN-ACTIVATOR; PLASMA-MEMBRANE; U937 MONOCYTES; ANTIGEN; MO3; DEGRADATION; PROTEOLYSIS AB We have studied expression of the urokinase receptor (u-PAR) in paraffin-embedded breast tissues at various stages of malignant progression. Forty-nine of 59 invasive cancers studied showed varying degrees of reactivity with our polyclonal antibody. The staining pattern was variable from case to case, although strong surface staining of tumor-associated macrophages was evident in most of these sections. In several cases, blood vessels in selected tumor areas were stained, as confirmed by treatment of adjacent sections with an anti-factor Vm antibody. These could represent regions of recent angiogenesis. Staining of tumor cells was observed in 21 of 59 cases and was extensive in 5 cases but confined to a small percentage of cells in the remaining 16 samples. In contrast with the cancer sections, all normal breast tissue (12 cases) was negative, as well as all fibroadenomas (4 cases), papillomas (5 cases), and hyperplasia with atypia (2 cases) studied. Seven carcinomas in situ examined were also negative for u-PAR, with the exception of few macrophages in two cases, suggesting that u-PAR expression may be associated with invasive tumor. The presence of u-PAR in human breast cancer and its absence from nonmalignant breast tissue supports the idea that plasminogen activation plays an important role in the process of cancer invasion. Expression of u-PAR on macrophages, endothelial cells, and cancer cells suggests the existence of complex paracrine interactions between tumor cells and stroma. C1 CALIFORNIA PACIFIC MED CTR RES INST,GERALDINE BUSH CANC RES INST,SAN FRANCISCO,CA 94115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV CALIF SAN FRANCISCO,CANC RES INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA. NR 29 TC 155 Z9 158 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 FEB 15 PY 1994 VL 54 IS 4 BP 861 EP 866 PG 6 WC Oncology SC Oncology GA MW686 UT WOS:A1994MW68600002 PM 8313371 ER PT J AU FREBOURG, T SADELAIN, M NG, YS KASSEL, J FRIEND, SH AF FREBOURG, T SADELAIN, M NG, YS KASSEL, J FRIEND, SH TI EQUAL TRANSCRIPTION OF WILD-TYPE AND MUTANT P53 USING BICISTRONIC VECTORS RESULTS IN THE WILD-TYPE PHENOTYPE SO CANCER RESEARCH LA English DT Note ID TUMOR SUPPRESSOR GENE; MUTATIONS; CANCER; PROTEIN; RAS; CELLS AB Somatic and germ-line mutations of p53 alleles inactivate the function of the protein. It has been suggested that mutant p53 can inactivate the wild-type protein and therefore have a trans-dominant negative effect. To investigate the interaction between wild-type and mutant proteins when both alleles are equally transcribed, me designed bicistronic vectors containing the internal ribosome entry site of the encephalomyocarditis virus and expressing wild-type and mutant p53. Analysis of the transcriptional activity and of the effect on cell growth of these plasmids indicates that the mutant protein is unable to completely suppress wild-type function. These results could explain why the inactivation of both p53 alleles is required in cancer development. C1 MASSACHUSETTS GEN HOSP,CTR CANC,DIV MOLEC GENET,BOSTON,MA 02129. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02114. NR 19 TC 56 Z9 57 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 FEB 15 PY 1994 VL 54 IS 4 BP 878 EP 881 PG 4 WC Oncology SC Oncology GA MW686 UT WOS:A1994MW68600006 PM 8313374 ER PT J AU PRICE, BD PARK, SJ AF PRICE, BD PARK, SJ TI DNA-DAMAGE INCREASES THE LEVELS OF MDM2 MESSENGER-RNA IN WTP53 HUMAN-CELLS SO CANCER RESEARCH LA English DT Note ID P53 PROTEIN; GENE AB Damage to chromosomal DNA increases the levels of the transcriptional regulatory protein p53. We have investigated how the MDM2 protein, which binds to p53 and inactivates its transcriptional activity, may be controlled following DNA damage. Irradiation of human GM2149 fibroblast cells causes an increase in MDM2 mRNA levels within 1 h, and levels remain elevated for at least 8 h. The induction of MDM2 mRNA following irradiation is not blocked by inhibitors of protein synthesis and can be detected after doses of 2-5 Gy. In ataxia telangiectasia cells or cells where p53 is mutated/deleted, MDM2 mRNA levels are not increased after DNA damage. This suggests that p53 is required for transcription of the MDM2 gene following DNA damage. RP PRICE, BD (reprint author), DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,STRESS PROT GRP,50 BINNEY ST,BOSTON,MA 02115, USA. NR 21 TC 84 Z9 85 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 FEB 15 PY 1994 VL 54 IS 4 BP 896 EP 899 PG 4 WC Oncology SC Oncology GA MW686 UT WOS:A1994MW68600010 PM 8313378 ER PT J AU KOYASU, S HUSSEY, RE CLAYTON, LK LERNER, A PEDERSEN, R DELANYHEIKEN, P CHAU, F REINHERZ, EL AF KOYASU, S HUSSEY, RE CLAYTON, LK LERNER, A PEDERSEN, R DELANYHEIKEN, P CHAU, F REINHERZ, EL TI TARGETED DISRUPTION WITHIN THE CD3-ZETA/ETA/THETA/OCT-1 LOCUS IN MOUSE SO EMBO JOURNAL LA English DT Article DE ANTISENSE RNA; GENE TARGETING; SPLICING; T CELL RECEPTOR; TRANSGENIC MOUSE ID T-CELL-RECEPTOR; DISULFIDE-LINKED DIMERS; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; ZETA-CHAIN; LYMPHOCYTES-T; GAMMA-DELTA; ETA-CHAIN; DIFFERENTIATION ANTIGENS; DEVELOPMENTAL BIOLOGY AB To elucidate the role of the CD3 eta subunit of the T cell receptor (TCR) in thymic development, a CD3 eta(-/-) mouse was generated by gene targeting. Insertion of a neomycin resistance gene into exon 9 of the CD3 zeta/eta/theta locus disrupted expression of CD3 eta and CD3 theta without affecting the expression of CD3 zeta. Little difference was observed between wild type and CD3 eta(-/-) mice with regard to cellularity or subset composition in thymus and peripheral lymphoid organs. Furthermore, neither alloproliferative responses nor cytotoxic T lymphocyte generation and effector function was affected by the mutation. The effect of the CD3 eta(-/-) mutation on thymic selection was examined by crossing the CD3 eta knockout animals with anti-HY TCR transgenic animals: the absence of the CD3 eta subunit altered neither positive nor negative selection. Thus, CD3 eta is not required for thymic selection. Of note, the birth rate of the CD3 eta(-/-) animals was significantly lower than that of wild type or heterozygous animals (P = 0.041-0.002). This unexpected result is probably the consequence of an alteration in mRNA expression of the Oct-1 nuclear transcription factor in CD3 eta(-/-) animals. The CD3 zeta/eta/theta locus partially overlaps the gene encoding Oct-1 whose transcription is dysregulated by the CD3 eta(-/-) mutation. Our results clearly underscore the value of characterizing all products of a genetic locus disrupted by gene targeting. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP KOYASU, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [AI19807, AI31269] NR 60 TC 35 Z9 35 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 15 PY 1994 VL 13 IS 4 BP 784 EP 797 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MX771 UT WOS:A1994MX77100007 PM 8112294 ER PT J AU HOLLANDER, GA WIDMER, B BURAKOFF, SJ AF HOLLANDER, GA WIDMER, B BURAKOFF, SJ TI LOSS OF NORMAL THYMIC REPERTOIRE SELECTION AND PERSISTENCE OF AUTOREACTIVE T-CELLS IN GRAFT-VS-HOST DISEASE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR V-BETA; MAMMARY-TUMOR VIRUS; BONE-MARROW TRANSPLANTATION; MLSA-ENCODED ANTIGENS; CLONAL DELETION; NEONATAL TOLERANCE; DENDRITIC CELLS; SELF-TOLERANCE; B-CELLS; SUPERANTIGEN MLS-1(A) AB To assess the influence of graft vs host disease (GVHD) on T cell development and thymic repertoire selection, a murine transplantation model was chosen, in which donor (B10.BR:Mls-1(b), Mls-2(b)) and recipient (CBA/J:Mls-1(a), Mls-2(a)) mice differ in their minor lymphocyte-stimulating Ag. Mature splenic T cells of donor origin were added to the T cell-depleted bone marrow cells to induce moderate GVHD. When analyzed 5 and 10 wk after transplantation, animals with GVHD, but not disease-free controls, demonstrated aberrant thymic maturation with an increase in single positive, TCR(high+) thymocytes. Phenotypic analysis of TCR V beta expression in mature thymocytes and peripheral T cells revealed a disruption of negative thymic selection of Mls-reactive T cells with the subsequent emergence of V beta 3(+) and V beta 6(+) T cells in mice with GVHD but not in controls. Using retroviral-mediated gene transfer to tag mature T cells, these V beta 3(+) and V beta 6(+) T cells could be shown to be derived from donor bone marrow precursors. Thymocytes expressing V beta 3 and V beta 6 were efficiently activated upon cross-linking of their TCRs and peripheral T cells from mice with GVHD proliferated to host-derived splenocytes in a MLR. When transferred to sublethally irradiated CBA/J recipients, only T cells from mice with GVHD expanded dramatically. These data suggest that the lack of proper thymic selection after bone marrow transplantation results in the survival and persistence of self-reactive T cells, which might be responsible for the autoimmune manifestations of chronic GVHD. RP HOLLANDER, GA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDAIT ONCOL,ROOM 1718,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01 CA39542-08A1] NR 55 TC 78 Z9 79 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 1994 VL 152 IS 4 BP 1609 EP 1617 PG 9 WC Immunology SC Immunology GA MY844 UT WOS:A1994MY84400012 PM 7907102 ER PT J AU RYAN, JJ KLEIN, KA NEUBERGER, TJ LEFTWICH, JA WESTIN, EH KAUMA, S FLETCHER, JA DEVRIES, GH HUFF, TF AF RYAN, JJ KLEIN, KA NEUBERGER, TJ LEFTWICH, JA WESTIN, EH KAUMA, S FLETCHER, JA DEVRIES, GH HUFF, TF TI ROLE FOR THE STEM-CELL FACTOR/KIT COMPLEX IN SCHWANN-CELL NEOPLASIA AND MAST-CELL PROLIFERATION-ASSOCIATED WITH NEUROFIBROMATOSIS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Note DE SCHWANN CELL; MAST CELL; NEUROFIBROMATOSIS; STEM CELL FACTOR; KIT; ONCOGENE ID C-KIT RECEPTOR; GTPASE ACTIVATING PROTEIN; GROWTH-FACTOR; PERIPHERAL-NERVE; TYROSINE-PHOSPHORYLATION; SACCHAROMYCES-CEREVISIAE; COMMITTED PROGENITOR; GENE-PRODUCT; CDNA CLONES; RAS GTPASE AB Schwann cells are the primary cell type in the disfiguring lesions associated with neurofibromatosis type 1 (NF-1). These lesions also contain abnormally high numbers of mast cells, a cell type which develops in response to stem cell factor. We report here that neonatal and adult rat and human Schwann cells, as well as a transfected rat Schwann cell line and a human Schwannoma line derived from an NF-1 patient, all produced stem cell factor mRNA and protein. In coculture experiments, surface expression of stem cell factor by neonatal rat Schwann cells was profoundly downregulated by contact with dorsal root ganglion neurites. The receptor for stem cell factor, KIT, was not expressed in normal Schwann cells but was expressed in the human Schwannoma line, suggesting that aberrant KIT expression may form an autocrine loop in certain Schwann cell neoplasias. (C) 1994 Wiley-Liss, Inc. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MICROBIOL & IMMUNOL,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOCHEM & MOLEC BIOPHYS,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT OBSTET & GYNECOL,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DIV HEMATOL & ONCOL,RICHMOND,VA 23298. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT PEDIAT ONCOL,BOSTON,MA. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NIAID NIH HHS [P50 AI28532, R01 AI-25537]; NINDS NIH HHS [NS 15408] NR 71 TC 66 Z9 66 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD FEB 15 PY 1994 VL 37 IS 3 BP 415 EP 432 DI 10.1002/jnr.490370314 PG 18 WC Neurosciences SC Neurosciences & Neurology GA MV899 UT WOS:A1994MV89900013 PM 7513766 ER PT J AU FORCE, T BONVENTRE, JV HEIDECKER, G RAPP, U AVRUCH, J KYRIAKIS, JM AF FORCE, T BONVENTRE, JV HEIDECKER, G RAPP, U AVRUCH, J KYRIAKIS, JM TI ENZYMATIC CHARACTERISTICS OF THE C-RAF-1 PROTEIN-KINASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAP KINASE; S6 KINASE; SIGNAL TRANSDUCTION; RAF-1 PROTOONCOGENE; C-JUN; PHOSPHORYLATION; ACTIVATION; PURIFICATION; RECEPTOR; INVITRO AB The c-Raf-1 protein kinase plays a central role in the mitogenic response of cells to growth factors, cytokines, and many oncogenes. Despite the critical importance of this enzyme, very little is known of its biochemical properties or mechanisms of regulation. In these experiments, we used the only candidate physiologic substrate identified as yet for c-Raf-1, mitogen-activated protein kinase kinase (MAPKK), to examine enzymatic characteristics and candidate modulators of c-Raf-1. c-Raf-1 was purified from Sf9 cells infected with recombinant baculovirus encoding a histidine-tagged c-Raf-1. The K-m values of c-Raf-1 for ATP and MAPKK were 11.6 mu M and 0.8 mu M, respectively, and the stoichiometry of phosphorylation of MAPKK by c-Raf-1 was 1.67 mol of phosphate per mol of MAPKK. In contrast to prior reports, Mg2+ was the preferred cation at Mg2+ and Mn2+ concentrations >5 mM. c-Raf-1 substrate specificity was extremely restricted, consistent with the identification of only one candidate physiologic substrate to date and highlighting the necessity of using MAPKK rather than artificial substrates in c-Raf-1 activity assays. Of multiple potential substrates tested, the only one phosphorylated to >20% of the level of MAPKK phosphorylation was myelin basic protein (22%). Heat-denatured MAPKK was phosphorylated at only 2% the level of native MAPKK, indicating that the restricted substrate specificity may be due to tertiary-structural requirements. We also examined whether c-Raf-1 activity is modulated by lipid binding to the cysteine finger region in its regulatory domain. Of multiple mitogen-stimulated or cell-membrane lipids tested, only phosphatidylserine and diacylglycerol in the presence of Ca2+ (2.5 mM) increased c-Raf-1 kinase activity significantly (1.5-fold). The increase is probably not of physiologic significance because it was about two orders of magnitude less than the stimulation of protein kinase C by these lipids. On gelfiltration chromatography, the peak of c-Raf-1 kinase activity and immunoreactivity eluted at a predicted molecular mass of >150 kDa, suggesting that active c-Raf-1 (but not inactive c-Raf-1) exists as a multimeric complex. This complex may not include p21(ras), however, because immunoreactive p21(ras) was not identified in the active fractions. C1 MASSACHUSETTS GEN HOSP,MED SERV,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,DIABET UNIT,BOSTON,MA 02114. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. RP FORCE, T (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,CARDIAC UNIT,BULFINCH 457,BOSTON,MA 02114, USA. OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [DK01986, DK39773] NR 41 TC 79 Z9 79 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 FEB 15 PY 1994 VL 91 IS 4 BP 1270 EP 1274 DI 10.1073/pnas.91.4.1270 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MX210 UT WOS:A1994MX21000017 PM 8108400 ER PT J AU SCHULICK, RD MULUK, SC CLERICI, M BERMAS, BL VIA, CS WEIR, MR SHEARER, GM AF SCHULICK, RD MULUK, SC CLERICI, M BERMAS, BL VIA, CS WEIR, MR SHEARER, GM TI VALUE OF IN-VITRO CD4(+) T-HELPER CELL-FUNCTION TEST FOR PREDICTING LONG-TERM LOSS OF HUMAN RENAL-ALLOGRAFTS SO TRANSPLANTATION LA English DT Note ID PATHWAYS C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NIGMS,PHARMACOL RES ASSOCIATE TRAINING PROGRAM,BETHESDA,MD. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. VET AFFAIRS MED CTR,RES SERV,DIV RHEUMATOL & CLIN IMMUNOL,BALTIMORE,MD. UNIV MARYLAND,SCH MED,DEPT MED,DIV NEPHROL,BALTIMORE,MD 21201. NR 7 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 1994 VL 57 IS 3 BP 480 EP 482 DI 10.1097/00007890-199402000-00035 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA MX020 UT WOS:A1994MX02000035 PM 7906443 ER PT J AU TRIGGS, WJ CALVANIO, R MACDONELL, RAL CROS, D CHIAPPA, KH AF TRIGGS, WJ CALVANIO, R MACDONELL, RAL CROS, D CHIAPPA, KH TI PHYSIOLOGICAL MOTOR ASYMMETRY IN HUMAN HANDEDNESS - EVIDENCE FROM TRANSCRANIAL MAGNETIC STIMULATION SO BRAIN RESEARCH LA English DT Article DE TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR SYSTEM; HANDEDNESS; ASYMMETRY; MOTOR EVOKED POTENTIAL ID ELECTRICAL-STIMULATION; BRAIN-STIMULATION; CEREBRAL-CORTEX; OWL MONKEYS; MUSCLE; COIL; HAND; RESPONSES; REORGANIZATION; APRAXIA AB We hypothesized that human handedness might be associated with measurable differences in the excitability of the motor system. We compared the thresholds for electromyographic activation of the left and right abductor pollicis brevis (APB) and biceps muscles in 30 left-handers and 30 right-handers, by varying the direction of a brief monophasic pulse in a circular electromagnetic coil centered over the vertex of the scalp. In right-handers, we found that the threshold for activation of muscles in the right arm was lower than the threshold for activation of corresponding muscles in the left arm. In left-handers, the reverse was true. Threshold asymmetry was influenced significantly by the consistency with which each subject used the writing hand to perform other motor tasks, and was not significant between non-consistent left-handers and right-handers. Our results indicate that human handedness, and in particular, consistency of hand preference, are associated with lateralized differences in the excitability of motor system projections activated by transcranial magnetic stimulation. Our findings might reflect physiological differences in corticospinal tract function or cortical motor representation. C1 SPAULDING REHABIL HOSP,DEPT NEUROPSYCHOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP TRIGGS, WJ (reprint author), UNIV FLORIDA,DEPT NEUROL,BOX 100236 JHMHC,GAINESVILLE,FL 32611, USA. NR 53 TC 118 Z9 119 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 FEB 14 PY 1994 VL 636 IS 2 BP 270 EP 276 DI 10.1016/0006-8993(94)91026-X PG 7 WC Neurosciences SC Neurosciences & Neurology GA MV905 UT WOS:A1994MV90500012 PM 8012811 ER PT J AU ARREGUI, A HOLLINGSWORTH, Z PENNEY, JB YOUNG, AB AF ARREGUI, A HOLLINGSWORTH, Z PENNEY, JB YOUNG, AB TI AUTORADIOGRAPHIC EVIDENCE FOR INCREASED DOPAMINE UPTAKE SITES IN STRIATUM OF HYPOXIC MICE SO NEUROSCIENCE LETTERS LA English DT Article DE DOPAMINE; DOPAMINE RECEPTOR; DOPAMINE UPTAKE SITE; HYPOXIA; COCAINE ID ANGIOTENSIN CONVERTING ENZYME; RAT NUCLEUS-ACCUMBENS; BRAIN; RECEPTORS; METABOLISM; GABA AB Ligand binding to dopamine uptake sites, D1 and D2 dopamine receptors was measured autoradiographically in brain sections of mice exposed to intermittent hypobaric hypoxia (450 Torr; 4,300 m) for 14 days and compared to sea level controls. Desipramine-insensitive [H-3]mazindol, [H-3]SCH23390 and [H-3]YM-09151-2 were used respectively for the labeling of the three binding sites. After 14 days, the striatum of hypoxic mice showed a significant 21% increase in dopamine uptake sites, one of the loci of action of cocaine. A similar (28%) but non-significant increase was found in the ventral tegmental area. No changes were seen in the activities of D1 or D2 receptors in several areas examined including the substantia nigra and the striatum. C1 MASSACHUSETTS GEN HOSP,DIV NEUROL,BOSTON,MA. RP ARREGUI, A (reprint author), UNIV PERUANA CAYETANO HEREDIA,DEPT NEUROL,APARTADO 27-0014,LIMA 27,PERU. FU NINDS NIH HHS [NS 19613] NR 21 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD FEB 14 PY 1994 VL 167 IS 1-2 BP 195 EP 197 DI 10.1016/0304-3940(94)91060-X PG 3 WC Neurosciences SC Neurosciences & Neurology GA MY131 UT WOS:A1994MY13100047 PM 8177524 ER PT J AU KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A BRADY, JN AF KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A BRADY, JN TI DIRECT INTERACTION OF HUMAN TFIID WITH THE HIV-1 TRANSACTIVATOR TAT SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 32 EP 32 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500110 ER PT J AU SHELDON, LA LARSON, JS KINGSTON, RE AF SHELDON, LA LARSON, JS KINGSTON, RE TI HYDROPHOBIC COILED-COIL DOMAINS REGULATE THE SUBCELLULAR-LOCALIZATION OF HUMAN HSF2 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 36 EP 36 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500126 ER PT J AU SHIRRA, M ZHU, Q VOLKER, J HUANG, HC PALLAS, D HANSEN, U AF SHIRRA, M ZHU, Q VOLKER, J HUANG, HC PALLAS, D HANSEN, U TI A NOVEL DIMERIZATION REGION IS DELETED IN THE PRODUCT ENCODED BY AN ALTERNATIVELY SPLICED MESSENGER-RNA FOR THE CELL-GROWTH REGULATED TRANSCRIPTION FACTOR LSF SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 37 EP 37 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500127 ER PT J AU GREEN, M NEWTON, E SCHUETZ, T KINGSTON, RE AF GREEN, M NEWTON, E SCHUETZ, T KINGSTON, RE TI HUMAN HSF1 CONTAINS A POTENT REGULATED ACTIVATION DOMAIN SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 45 EP 45 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500159 ER PT J AU HANSEN, U RIMSKY, S BATSON, SC BUSTIN, M DING, HF AF HANSEN, U RIMSKY, S BATSON, SC BUSTIN, M DING, HF TI CHROMOSOMAL PROTEIN HMG-14 INCREASES THE RATE OF TRANSCRIPTIONAL ELONGATION BY RNA-POLYMERASE-II ON CHROMATIN TEMPLATES SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. NCI,BETHESDA,MD 20892. RI Bustin, Michael/G-6155-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 59 EP 59 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500216 ER PT J AU SILVER, PA BOSSIE, M FLACH, J VOGEL, J JINKS, T GORSCH, L COLE, CN SCHLENSTEDT, G AF SILVER, PA BOSSIE, M FLACH, J VOGEL, J JINKS, T GORSCH, L COLE, CN SCHLENSTEDT, G TI MOVEMENT OF MACROMOLECULES IN AND OUT OF THE YEAST NUCLEUS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. DARTMOUTH COLL,SCH MED,HANOVER,NH. NR 2 TC 0 Z9 0 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 79 EP 79 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500281 ER PT J AU BERNARDS, A THE, I HANNIGAN, G MURTHY, A GUSELLA, J HARIHARAN, I AF BERNARDS, A THE, I HANNIGAN, G MURTHY, A GUSELLA, J HARIHARAN, I TI TOWARDS A GENETIC-ANALYSIS OF NEUROFIBROMATOSIS TYPE-1 GENE-FUNCTION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02129. RI The, Inge/B-8884-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 160 EP 160 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500566 ER PT J AU JACOBY, LB MACCOLLIN, M LOUIS, DN TROFATTER, JA KLEY, N SEIZINGER, B RAMESH, V GUSELLA, JF AF JACOBY, LB MACCOLLIN, M LOUIS, DN TROFATTER, JA KLEY, N SEIZINGER, B RAMESH, V GUSELLA, JF TI THE MERLIN TUMOR-SUPPRESSOR IN NEUROFIBROMATOSIS-2 SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 163 EP 163 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500575 ER PT J AU ENGLERT, C MAHESWARAN, S BENNETT, P HABER, D AF ENGLERT, C MAHESWARAN, S BENNETT, P HABER, D TI THE WT1 GENE-PRODUCT FORMS A COMPLEX WITH P53 IN WILMS-TUMORS AND IN STABLY TRANSFECTED BABY RAT-KIDNEY CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CTR CANC,GENET MOLEC LAB,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 176 EP 176 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500620 ER PT J AU KLEY, N BIANCHI, A HARA, T KLEINSZANTO, A RAMESH, V GUSELLA, JF DEPREZ, RL ZWARTHOFF, E SEIZINGER, BR AF KLEY, N BIANCHI, A HARA, T KLEINSZANTO, A RAMESH, V GUSELLA, JF DEPREZ, RL ZWARTHOFF, E SEIZINGER, BR TI THE NF2 TUMOR-SUPPRESSOR GENE - MUTATIONS IN MULTIPLE TUMOR TYPES AND INITIAL CHARACTERIZATION OF ITS ENCODED PRODUCT SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC GENET & CELL BIOL,PRINCETON,NJ 08543. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02129. ERASMUS UNIV ROTTERDAM,DEPT PATHOL,3000 DR ROTTERDAM,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 189 EP 189 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500673 ER PT J AU MARUTA, H VARGA, M RAMESH, V GUSELLA, J AF MARUTA, H VARGA, M RAMESH, V GUSELLA, J TI THE TUMOR SUPPRESSORS NF1 AND NF2 - ACTIONS AND FUNCTIONAL DOMAINS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. LUDWIG INST CANC RES,MELBOURNE,AUSTRALIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 190 EP 190 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500675 ER PT J AU LOW, KG CHU, HM TAN, Y SCHWARTZ, PM DANIELS, GM MELNER, MH COMB, MJ AF LOW, KG CHU, HM TAN, Y SCHWARTZ, PM DANIELS, GM MELNER, MH COMB, MJ TI AMINO-TERMINAL DOMAIN OF ATF3 MEDIATES HTLV-1 TAX-DEPENDENT TRANSACTIVATION OF GENE-TRANSCRIPTION SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROBIOL LAB,BOSTON,MA 02129. OREGON HLTH SCI UNIV,DEPT CELL BIOL & ANAT,PORTLAND,OR 97201. VANDERBILT UNIV,DEPT OBSTET,NASHVILLE,TN 37232. VANDERBILT UNIV,DEPT GYNECOL,NASHVILLE,TN 37232. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD FEB 13 PY 1994 SU 18C BP 215 EP 215 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MY175 UT WOS:A1994MY17500765 ER PT J AU GOLDHIRSCH, A GELBER, RD PRICE, KN CASTIGLIONE, M COATES, AS RUDENSTAM, CM COLLINS, J LINDTNER, J HACKING, A MARINI, G BYRNE, M CORTESFUNES, H SCHNURCH, G BRUNNER, KW TATTERSALL, MHN FORBES, J SENN, HJ AF GOLDHIRSCH, A GELBER, RD PRICE, KN CASTIGLIONE, M COATES, AS RUDENSTAM, CM COLLINS, J LINDTNER, J HACKING, A MARINI, G BYRNE, M CORTESFUNES, H SCHNURCH, G BRUNNER, KW TATTERSALL, MHN FORBES, J SENN, HJ TI EFFECT OF SYSTEMIC ADJUVANT TREATMENT ON FIRST SITES OF BREAST-CANCER RELAPSE SO LANCET LA English DT Article ID PAST DECADE AB Adjuvant systemic treatment for resectable breast cancer changes the natural history of the disease but provides only a small and delayed effect on survival. Evaluation of the types of first relapse avoided by available treatments may explain why effects on mortality are small and appear late during follow-up. In randomised clinical trials done by the International Breast Cancer Study Group (IBCSG) between 1978 and 1985, 2108 patients with node-positive disease received more-effective treatments (6 or more cycles of cyclophosphamide, methotrexate, fluorouracil and prednisone; with or without tamoxifen, or tamoxifen and prednisone alone), and 722 patients received less-effective treatments (no treatment or a single cycle of chemotherapy). 3 main categories of first site of relapse were defined and evaluated by cumulative incidence analysis: local or regional, and distant soft tissue,bone, and viscera. The more-effective treatments reduced the cumulative incidence of first relapse in local or regional and distant soft tissue sites at 10 years from 36% to 18% (p=00001); first relapse in bone and viscera was not altered by the more-effective treatments. These results were similar for premenopausal and postmenopausal women, and for patients with oestrogen-receptor-positive or oestrogen-receptor-negative tumours. Adjuvant systemic treatments in current use improve patient outcome mainly by reducing the incidence of first local or regional and distant soft-tissue relapses, while first recurrences in bone or viscera are influenced much less. More intensive treatments at present being tested in clinical trials might affect bone and visceral relapses and have a greater and earlier influence on survival. C1 DANA FARBER CANC INST,INT BREAST CANC STUDY GRP STAT CTR,DIV BIOSTAT,BOSTON,MA 02115. OSPED CIVICO,LUGANO,SWITZERLAND. IBCSG COORDINATING CTR,BERN,SWITZERLAND. ROYAL PRINCE ALFRED HOSP,CAMPERDOWN,NSW,AUSTRALIA. SAHLGRENS UNIV HOSP,GOTHENBURG,SWEDEN. ANTICANC COUNCIL VICTORIA,CARLTON,VIC,AUSTRALIA. INST ONCOL,LJUBLJANA,SLOVENIA. GROOTE SCHUUR HOSP,CAPE TOWN,SOUTH AFRICA. SPEDALI CIVIL BRESCIA,BRESCIA,ITALY. SIR CHARLES GALRDNER HOSP,NEDLANDS,WA,AUSTRALIA. MADRID BREAST CANC GRP,MADRID,SPAIN. UNIV DUSSELDORF,DUSSELDORF,GERMANY. INSELSPITAL BERN,CH-3010 BERN,SWITZERLAND. ROYAL PRINCE ALFRED HOSP,CAMPERDOWN,NSW,AUSTRALIA. MATER MISERICORDLAE HOSP,WARATAH,NSW,AUSTRALIA. KANTONSSPITAL,ST GALLEN,SWITZERLAND. NR 27 TC 62 Z9 64 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD FEB 12 PY 1994 VL 343 IS 8894 BP 377 EP 381 DI 10.1016/S0140-6736(94)91221-1 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MW283 UT WOS:A1994MW28300007 PM 7905550 ER PT J AU TSAKAYANNIS, D LI, WW RAZVI, S SPIRITO, N AF TSAKAYANNIS, D LI, WW RAZVI, S SPIRITO, N TI SUCRALFATE AND CHRONIC VENOUS STASIS ULCERS SO LANCET LA English DT Letter C1 MASSACHUSETTS GEN HOSP, DIV MED SERV, BOSTON, MA USA. RP TSAKAYANNIS, D (reprint author), ST ELIZABETHS MED CTR, DEPT SURG, BOSTON, MA 02135 USA. NR 5 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD FEB 12 PY 1994 VL 343 IS 8894 BP 424 EP 425 DI 10.1016/S0140-6736(94)91263-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MW283 UT WOS:A1994MW28300056 PM 7905584 ER PT J AU ALBERTA, JA RUNDELL, K STILES, CD AF ALBERTA, JA RUNDELL, K STILES, CD TI IDENTIFICATION OF AN ACTIVITY THAT INTERACTS WITH THE 3'-UNTRANSLATED REGION OF C-MYC MESSENGER-RNA AND THE ROLE OF ITS TARGET SEQUENCE IN MEDIATING RAPID MESSENGER-RNA DEGRADATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA DEGRADATION; 3' UNTRANSLATED REGION; URIDINE BINDING-FACTOR; CELL-FREE SYSTEM; RICH SEQUENCES; NUCLEOTIDE-SEQUENCE; STABILITY INVITRO; GENE-EXPRESSION; CODING REGION; 1ST STEP AB Single or multiple copies of the pentameric motif, AUUUA, are found in the 3'-untranslated domain of most immediate early mRNAs. A broad body of data links this 5-base element to the selective degradation of these mRNAs. However, AUUUA motifs are neither always necessary nor always sufficient to tag an mRNA for rapid degradation. Here, we describe a cytoplasmic, protease-sensitive factor in Balb/c3T3 cells that interacts with the 3'-untranslated region of c-myc mRNA. The factor recognizes a 39-base uridine-rich domain adjacent to, but distinct from, the c-mye AUUUA motif. In chimeric mRNA constructs, the 39-base binding element cooperates with adjacent sequence material to destabilize beta-globin mRNA. C1 DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. NORTHWESTERN UNIV,SCH MED,DEPT MICROBIOL IMMUNOL,CHICAGO,IL 60611. FU NCI NIH HHS [CA22042] NR 48 TC 56 Z9 57 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 FEB 11 PY 1994 VL 269 IS 6 BP 4532 EP 4538 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MW989 UT WOS:A1994MW98900095 PM 8308023 ER PT J AU LUISIDELUCA, C KOLODNER, R AF LUISIDELUCA, C KOLODNER, R TI PURIFICATION AND CHARACTERIZATION OF THE ESCHERICHIA-COLI RECO PROTEIN - RENATURATION OF COMPLEMENTARY SINGLE-STRANDED-DNA MOLECULES CATALYZED BY THE RECO PROTEIN SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RECOMBINATION; REPAIR; DNA RENATURATION; RECF PATHWAY; RECO PROTEIN ID SACCHAROMYCES-CEREVISIAE; BINDING-PROTEIN; GENETIC-RECOMBINATION; PLASMID RECOMBINATION; EXONUCLEASE-VIII; BETA-PROTEIN; PHAGE-LAMBDA; EXCHANGE; K-12; MECHANISM C1 DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP LUISIDELUCA, C (reprint author), UNIV PITTSBURGH,SCH MED,DEPT MOLEC GENET & BIOCHEM,W1151 BIOMED SCI TOWER,PITTSBURGH,PA 15261, USA. FU NIGMS NIH HHS [GM26017] NR 47 TC 61 Z9 62 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD FEB 11 PY 1994 VL 236 IS 1 BP 124 EP 138 DI 10.1006/jmbi.1994.1123 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MW687 UT WOS:A1994MW68700012 PM 8107098 ER PT J AU GAGLIARDINI, V FERNANDEZ, PA LEE, RKK DREXLER, HCA ROTELLO, RJ FISHMAN, MC YUAN, J AF GAGLIARDINI, V FERNANDEZ, PA LEE, RKK DREXLER, HCA ROTELLO, RJ FISHMAN, MC YUAN, J TI PREVENTION OF VERTEBRATE NEURONAL DEATH BY THE CRMA GENE SO SCIENCE LA English DT Article ID PROGRAMMED CELL-DEATH; PROTEIN-PRECURSOR; RNA-SYNTHESIS; BCL-2; INTERLEUKIN-1; EXPRESSION; SURVIVAL AB Interleukin-1beta converting enzyme (ICE) is a mammalian homolog of CED-3, a protein required for programmed cell death in the nematode Caenorhabditis elegans. The activity of ICE can be specifically inhibited by the product of crmA, a cytokine response modifier gene encoded by cowpox virus. Microinjection of the crmA gene into chicken dorsal root ganglion neurons was found to prevent cell death induced by deprivation of nerve growth factor. Thus, ICE is likely to participate in neuronal death in vertebrates. C1 MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,149 13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 21 TC 607 Z9 611 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 FEB 11 PY 1994 VL 263 IS 5148 BP 826 EP 828 DI 10.1126/science.8303301 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MV866 UT WOS:A1994MV86600041 PM 8303301 ER PT J AU JENSEN, DM CHENG, S KOVACS, TOG RANDALL, G JENSEN, ME REEDY, T FRANKL, H MACHICADO, G SMITH, J SILPA, M VANDEVENTER, G AF JENSEN, DM CHENG, S KOVACS, TOG RANDALL, G JENSEN, ME REEDY, T FRANKL, H MACHICADO, G SMITH, J SILPA, M VANDEVENTER, G TI A CONTROLLED-STUDY OF RANITIDINE FOR THE PREVENTION OF RECURRENT HEMORRHAGE FROM DUODENAL-ULCER SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BLEEDING PEPTIC-ULCERS; HISTAMINE2-RECEPTOR ANTAGONISTS; MAINTENANCE TREATMENT; STANDARD THERAPY; CONTROLLED TRIAL; DRUG-THERAPY; CIMETIDINE; MULTICENTER; DISEASE; RELAPSE AB Background. Hemorrhage is the most common complication of duodenal ulcer disease, but there is little information about the effectiveness and safety of long-term maintenance therapy with histamine H-2-receptor blockers. Methods. We conducted a double-blind study in patients with endoscopically documented hemorrhage from duodenal ulcers. Patients were randomly assigned to maintenance therapy with ranitidine (150 mg at night) or placebo and were followed for up to three years. Endoscopy was performed at base line (to document that the ulcers had healed), at exit from the study, and when a patient had persistent ulcer symptoms unrelieved by antacids or had gastrointestinal bleeding. Symptomatic relapses without bleeding were treated with ranitidine; if the ulcer healed within eight weeks, the patient resumed taking the assigned study medication. Results. The two groups were similar at entry, which usually occurred about three months after the index hemorrhage. After a mean follow-up of 61 weeks, 3 of the 32 patients treated with ranitidine had recurrent hemorrhage, as compared with 12 of the 33 given placebo (P<0.05). Half the episodes of recurrent bleeding were asymptomatic. One patient in the ranitidine group withdrew from the study because of asymptomatic thrombocytopenia during the first month. Conclusions. For patients whose duodenal ulcers heal after severe hemorrhage, long-term maintenance therapy with ranitidine is safe and reduces the risk of recurrent bleeding. C1 UNIV CALIF LOS ANGELES, CTR ULCER RES & EDUC, LOS ANGELES, CA 90024 USA. W LOS ANGELES VET AFFAIRS MED CTR, LOS ANGELES, CA USA. VALLEY MED CTR, VAN NUYS, CA USA. ALTON OCHSNER MED FDN & OCHSNER CLIN, NEW ORLEANS, LA 70121 USA. HIGHLAND HOSP, OAKLAND, CA USA. RI smith, james/C-9922-2016 FU NIADDK NIH HHS [AM 41301, AM 33273] NR 27 TC 101 Z9 103 U1 0 U2 0 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 FEB 10 PY 1994 VL 330 IS 6 BP 382 EP 386 DI 10.1056/NEJM199402103300602 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MV279 UT WOS:A1994MV27900002 PM 8284002 ER PT J AU VONREYN, CF BROWN, ST ARBEIT, RD AF VONREYN, CF BROWN, ST ARBEIT, RD TI RIFABUTIN PROPHYLAXIS AGAINST MYCOBACTERIUM-AVIUM COMPLEX INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 BRONX VET AFFAIRS MED CTR,BRONX,NY 10468. BOSTON VET AFFAIRS MED CTR,BOSTON,MA 02130. RP VONREYN, CF (reprint author), DARTMOUTH COLL,HITCHCOCK MED CTR,HANOVER,NH 03756, USA. NR 2 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 FEB 10 PY 1994 VL 330 IS 6 BP 437 EP 437 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA MV279 UT WOS:A1994MV27900026 PM 8129826 ER PT J AU JOHNSON, AW KOLODNER, RD AF JOHNSON, AW KOLODNER, RD TI THE ACTIVITY OF THE SACCHAROMYCES-CEREVISIAE STRAND EXCHANGE PROTEIN-1 INTRINSIC EXONUCLEASE DURING JOINT MOLECULE FORMATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLI RECA PROTEIN; ESCHERICHIA-COLI; HOMOLOGOUS RECOMBINATION; DUPLEX DNA; GENETIC-RECOMBINATION; BETA-PROTEIN; BREAKS; MODEL; PURIFICATION; RENATURATION AB Strand exchange protein 1 (Sep1) from Saccharomyces cerevisiae catalyzes the formation of heteroduplex DNA from single-stranded and homologous linear duplex DNA. The initial pairing reaction requires limited exonucleolytic digestion of the double-stranded DNA (dsDNA) by the intrinsic 5' to 3' exonuclease of Sep1 or by an exogenous exonuclease. Subsequent strand exchange proceeds without the need for exonuclease activity. Sep1 degrades linear dsDNA at a rate of 20 nucleotides/min with an average processivity of 45 nucleotides. During strand exchange reactions joint molecules are first observed after 1-2 min, suggesting that only limited digestion is necessary for pairing. The linear dsDNA was found to pair with single-stranded DNA (ssDNA) when it was resected by only 22 nucleotides, and linear dsDNA digested by more than 22 nucleotides was observed only in joint molecules. Approximately 20 nucleotides were also the minimum extent of digestion that could support pairing. In the absence of exonuclease activity, Sep1-promoted pairing requires dsDNA molecules with single-stranded tails homologous to the circular ssDNA. These results suggest that Sep1-promoted strand exchange requires a single-strand annealing event prior to the strand displacement phase of the reaction. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIGMS NIH HHS [GM29383, GM13594] NR 46 TC 11 Z9 12 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 FEB 4 PY 1994 VL 269 IS 5 BP 3664 EP 3672 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MV631 UT WOS:A1994MV63100079 PM 8106411 ER PT J AU JOHNSON, AW KOLODNER, RD AF JOHNSON, AW KOLODNER, RD TI CHARACTERIZATION OF THE INTERACTION OF SACCHAROMYCES-CEREVISIAE STRAND EXCHANGE PROTEIN-1 WITH DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLI RECA-PROTEIN; ESCHERICHIA-COLI; BINDING; RECOMBINATION; PURIFICATION; MOLECULES; SYNAPSIS; JOINTS AB We have analyzed in greater detail the interaction of strand exchange protein 1 (Sep1) from Saccharomyces cerevisiae with DNA. The binding site size of Sep1 on single-stranded DNA (ssDNA) was determined to be 70 nucleotides per protein monomer using a fluorescence assay and 100 nucleotides using an exonuclease titration technique. The amount of Sep1 required for maximum aggregation of ssDNA was the amount needed to saturate the DNA. When double-stranded DNA (dsDNA) and ssDNA were both present, the duplex DNA was efficiently aggregated only at protein concentrations above that required for saturation of ssDNA. Strand exchange reactions with blunt-ended linear dsDNA and homologous ssDNA substrates required saturation of the ssDNA with Sep1 since free Sep1 is needed for exonuclease activity to initiate pairing with the dsDNA substrate. Preincubation of Sep1 with resected duplex DNA before adding ssDNA allowed joint molecule formation to occur at protein concentrations at least 10-fold below that required for saturation of the ssDNA. However, preincubation of Sep1 with ssDNA before the addition of resected duplex DNA required saturating amounts of Sep1 for joint molecule formation to occur. These results suggest that pairing requires Sep1 on both the ssDNA and the resected ends of the dsDNA. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NIGMS NIH HHS [GM13594, GM29383] NR 32 TC 7 Z9 8 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 FEB 4 PY 1994 VL 269 IS 5 BP 3673 EP 3681 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MV631 UT WOS:A1994MV63100080 PM 8106412 ER PT J AU LEVINE, BW NICKELEIT, V BHALLA, M MARK, EJ JOSEPH, PM HARRIS, SE AF LEVINE, BW NICKELEIT, V BHALLA, M MARK, EJ JOSEPH, PM HARRIS, SE TI A 34-YEAR-OLD WOMAN WITH MILD EXERTIONAL DYSPNEA AND INTERSTITIAL PULMONARY-LESIONS - PULMONARY EOSINOPHILIC GRANULOMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID HIGH-RESOLUTION CT; HISTIOCYTOSIS-X CELLS; LUNG-DISEASE; LANGERHANS CELLS; ADULT C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP LEVINE, BW (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 39 TC 1 Z9 1 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 FEB 3 PY 1994 VL 330 IS 5 BP 347 EP 353 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MU489 UT WOS:A1994MU48900010 ER PT J AU HARRIS, WH AF HARRIS, WH TI OSTEOLYSIS AND PARTICLE DISEASE IN HIP-REPLACEMENT - A REVIEW SO ACTA ORTHOPAEDICA SCANDINAVICA LA English DT Review ID IMPROVED CEMENTING TECHNIQUES; SYNOVIAL-LIKE MEMBRANE; 10-YEAR FOLLOW-UP; BONE-RESORPTION; ARTHROPLASTY; WEAR; PROSTHESES; PROGNOSIS; INTERFACE; SIMULATOR C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT ORTHOPED, HIP & IMPLANT UNIT, BOSTON, MA 02114 USA. RP MASSACHUSETTS GEN HOSP, ORTHOPED BIOMECH LAB, JACKSON 1126, 32 FRUIT ST, BOSTON, MA 02114 USA. NR 76 TC 211 Z9 216 U1 0 U2 7 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0001-6470 J9 ACTA ORTHOP SCAND JI Acta Orthop. Scand. PD FEB PY 1994 VL 65 IS 1 BP 113 EP 123 DI 10.3109/17453679408993734 PG 11 WC Orthopedics SC Orthopedics GA ND881 UT WOS:A1994ND88100029 PM 8154274 ER PT J AU ISRAEL, DH SHARMA, SK FUSTER, V AF ISRAEL, DH SHARMA, SK FUSTER, V TI ANTITHROMBOTIC THERAPY IN PROSTHETIC HEART-VALVE REPLACEMENT SO AMERICAN HEART JOURNAL LA English DT Article ID PLATELET SURVIVAL TIME; 10 YEARS EXPERIENCE; TERM FOLLOW-UP; STARR-EDWARDS; BJORK-SHILEY; THROMBOEMBOLIC COMPLICATIONS; PORCINE BIOPROSTHESIS; ANTICOAGULANT-THERAPY; VALVULAR PROSTHESIS; CARDIAC VALVES C1 MT SINAI MED CTR,NEW YORK,NY 10029. CARDIOL ASSOCIATES NEW HAVEN PC,NEW HAVEN,CT. MASSACHUSETTS GEN HOSP,BOSTON,MA. RI Fuster, Valentin/H-4319-2015; OI Fuster, Valentin/0000-0002-9043-9986; Sharma, Sanjeev Kumar/0000-0002-3273-0708 NR 88 TC 15 Z9 16 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD FEB PY 1994 VL 127 IS 2 BP 400 EP 411 DI 10.1016/0002-8703(94)90131-7 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MV483 UT WOS:A1994MV48300022 PM 8296709 ER PT J AU ELIAS, AD SKARIN, AT GONIN, R OLIYNYK, P STOMPER, PC OHARA, C SOCINSKI, MA SHELDON, T MAGGS, P FREI, E AF ELIAS, AD SKARIN, AT GONIN, R OLIYNYK, P STOMPER, PC OHARA, C SOCINSKI, MA SHELDON, T MAGGS, P FREI, E TI NEOADJUVANT TREATMENT OF STAGE IIIA NONSMALL CELL LUNG-CANCER - LONG-TERM RESULTS SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE LUNG CANCER; LOCOREGIONAL THERAPY; LONG-TERM FOLLOW-UP ID CHEMOTHERAPY; CARCINOMA; RADIATION; SURGERY; THERAPY; TRIALS AB The multimodality approach to locally advanced Stage III non-small cell lung cancer is continuing to evolve. In this trial, 54 patients with surgically staged IIIA disease were treated with neoadjuvant chemotherapy, surgical resection, and chest radiotherapy. Response to four cycles of CAP chemotherapy (cyclophosphamide, doxorubicin. cisplatin) was 39% (8% complete responses). One septic death occurred. Thoracotomy was performed on 31 patients, of whom 29 (56%) were resected and 24 (44%) were completely resected. Complete resections were more frequently observed in chemotherapy responders. Extranodal mediastinal extension in nonresponding patients was the most frequent reason not to attempt thoracotomy. The overall median times to progression and survival were 11.6 (.7-66.5) and 17.9 (2.8-71.4) months. Long-term disease-free survival was observed in 11 patients (20%) with a median follow-up of 46.5 (24-71) months. All these patients underwent complete resection and constitute 46% of the patients undergoing complete resection. Median times to progression and survival were 33.4 (5.0-66.5) and 33.5 (10-71.4) months for completely resected patients. Although the ability to perform surgery identified a population that has favorable locoregional control and disease-free survival, distant relapse continues to represent the major obstacle to enhanced survival in resected patients. Unresected patients, however, are likely to relapse in both local and distant sites. Response to chemotherapy may not only enhance systemic control, but may also increase the probability of complete resection. Randomized trials should be conducted to evaluate the role of individual modalities (surgery, chemotherapy, or radiotherapy) while applying the remaining modalities maximally. The temptation to compare different treatment approaches should be resisted. C1 NEW ENGLAND BAPTIST HOSP,DEPT SURG,BOSTON,MA. NEW ENGLAND DEACONESS HOSP,JOINT CTR RADIAT THERAPY,BOSTON,MA 02215. NEW ENGLAND DEACONESS HOSP,DIV PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MICROBIOL & PUBL HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV ONCORADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP ELIAS, AD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CLIN ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 35 TC 29 Z9 30 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 1994 VL 17 IS 1 BP 26 EP 36 DI 10.1097/00000421-199402000-00007 PG 11 WC Oncology SC Oncology GA MX237 UT WOS:A1994MX23700007 PM 8311004 ER PT J AU KOCH, AE NICKOLOFF, BJ HOLGERSSON, J SEED, B HAINES, GK BURROWS, JC LEIBOVICH, SJ AF KOCH, AE NICKOLOFF, BJ HOLGERSSON, J SEED, B HAINES, GK BURROWS, JC LEIBOVICH, SJ TI 4A11, A MONOCLONAL-ANTIBODY RECOGNIZING A NOVEL ANTIGEN EXPRESSED ON ABERRANT VASCULAR ENDOTHELIUM - UP-REGULATION OF AN IN-VIVO MODEL CONTACT-DERMATITIS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; SYNOVIAL TISSUE MACROPHAGES; STIMULATORY FACTOR-II; SIALYL-LEWIS-X; RHEUMATOID-ARTHRITIS; CELL-ADHESION; STRUCTURAL CHARACTERIZATION; CARBOHYDRATE LIGAND; INFLAMED SYNOVIUM; RHUS-DERMATITIS AB We describe the production and characterization of a novel monoclonal antibody (MAb) that recognizes a human endothelial cell antigen expressed mainly in inflamed and malignant disease states. We have used immunohistochemistry to determine the spectrum of reactivity of this MAb compared with that of a MAb to factor VIII-related antigen (MAb FVIII). MAb 4A11 does not react with several myeloid or lymphoid cell lines or with peripheral blood cells. Unlike MAb FVIII, MAb 4A11 does not react with platelets. MAb 4A11 reacts with most vascular endothelial cells in lymphoid tissue but with few (< 10%) endothelial cells in thymus, spleen, liver, lung, adrenal gland, placenta, testes, and stilt. MAb 4A11 detects endothelial cells in diseased tissues such as rheumatoid and osteoarthritic synovium and psoriatic stilt. Vascular endothelial cells in both adrenal tumors and cutaneous Kaposi's sarcomas lesions are MAb 4A11 reactive. In vitro the 4A11 antigen is not detectable on cultured human umbilical vein endothelial cells and its expression is not induced on these cells by treatment with lipopolysaccharide, interferon-gamma, interleukin-1 and -6, or tumor necrosis factor-alpha. However, in an in vivo model of allergic contact dermatitis the 4A11 antigen is upregulated differentially front other endothelial markers such as E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1. In this dermal model of inflammation, poison ivy extract is applied to the skin and biopsies taken at 0, 6, and 24 hours. In addition to focal keratinocyte expression, 4A11 antigen is found on 11% of dermal endothelial cells at time 0 and antigen expression increases with time until 24 hours, when 4A11 antigen is present on 63% of the endothelial cells. Using thin layer chromatography, MAb 4A11 reacts with the H-5-2 [Fuc alpha 2Gal beta 4GlcNAc beta 3Gal beta 4Glc beta 1Cer] and Lewis(y)-6 [Fuc alpha 2Gal beta 4(Fuc alpha 3)GlcNAc beta 3Gal beta 4Glc beta 1Cer] blood group glycolipids. The presence of the novel 4A11 antigen in inflamed and malignant tissues containing many blood vessels and its differential upregulation in allergic contact dermatitis may signify an important function for this antigen in the inflammatory process. C1 NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH MED,DEPT MOLEC BIOL,CHICAGO,IL. NORTHWESTERN UNIV,SCH MED,DEPT BASIC SCI,CHICAGO,IL. NORTHWESTERN UNIV,SCH DENT,DEPT MED,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH DENT,DEPT PATHOL,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH DENT,DEPT MOLEC BIOL,CHICAGO,IL 60611. NORTHWESTERN UNIV,SCH DENT,DEPT BASIC SCI,CHICAGO,IL 60611. LAKESIDE VET ADM MED CTR,CHICAGO,IL. MASSACHUSETTS GEN HOSP,BOSTON,MA. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI. RP KOCH, AE (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT MED,303 E CHICAGO AVE,WARD BLDG 3-315,CHICAGO,IL 60611, USA. RI Koch, Alisa/B-6894-2011 FU NIAMS NIH HHS [AR30692, AR41492]; NIGMS NIH HHS [GM29135] NR 72 TC 27 Z9 27 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1994 VL 144 IS 2 BP 244 EP 259 PG 16 WC Pathology SC Pathology GA MW116 UT WOS:A1994MW11600006 PM 8311112 ER PT J AU RUSSELL, PS CHASE, CM WINN, HJ COLVIN, RB AF RUSSELL, PS CHASE, CM WINN, HJ COLVIN, RB TI CORONARY ATHEROSCLEROSIS IN TRANSPLANTED MOUSE HEARTS .1. TIME-COURSE AND IMMUNOGENETIC AND IMMUNOPATHOLOGICAL CONSIDERATIONS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RABBIT CARDIAC ALLOGRAFTS; GRAFT ARTERIOSCLEROSIS; NON-H-2 ANTIGENS; ARTERY DISEASE; INBRED STRAINS; LONG-TERM; CLASS-I; REJECTION; MICE; MODEL AB An experimental system is described ill which coronary arteries of mouse hearts transplanted heterotopically develop obstructive lesions by 4 weeks. Transient immunosuppression permits graft survival. Donor/recipient antigenic differences may be either class I or class II major histocompatibility antigens (H-2) or non-H-2 antigens. An infiltrate including CD4(+) and CD8(+) T lymphocytes and macrophages concentrates early, in the intima and adventitia of larger coronary arteries, with little in the myocardium. Subsequently, the intima expands with cells of donor origin and the infiltrate invades the media. Endothelial and intimal cells express ICAM-1, leukocytes LFA-1. Endothelium expresses class I, but not class II, antigens. As class II disparity alone suffices, the endothelium can apparently be all indirect target of immune injury. We propose that graft atherosclerosis is T cell initiated and elicited by heterogeneous antigens in the endothelium or media. It is separable from rejection of the myocardium. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP RUSSELL, PS (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [R0-1 HL43340] NR 50 TC 127 Z9 129 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 1994 VL 144 IS 2 BP 260 EP 274 PG 15 WC Pathology SC Pathology GA MW116 UT WOS:A1994MW11600007 PM 7906094 ER PT J AU DOSANJH, A LENCER, W BROWN, D AUSIELLO, DA STOW, JL AF DOSANJH, A LENCER, W BROWN, D AUSIELLO, DA STOW, JL TI HETEROLOGOUS EXPRESSION OF DELTA-F508 CFTR RESULTS IN DECREASED SIALYLATION OF MEMBRANE GLYCOCONJUGATES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; LECTINS; GLYCOSYLATION ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS FIBROBLASTS; NIGRA L BARK; CHOLERA-TOXIN; CHLORIDE CONDUCTANCE; EPITHELIAL-CELLS; ESCHERICHIA-COLI; ACIDIFICATION; BINDING; GLYCOPROTEINS AB The cystic fibrosis transmembrane conductance regulator (CFTR) is commonly mutated in cystic fibrosis to the Delta F508 CFTR. CFTR has been shown to function as a adenosine 3',5'-cyclic monophosphate-dependent Cl- channel at the cell surface, and there is evidence to suggest that CFTR may also haw a role in transmembrane Cl- conductance in intracellular membrane compartments. Studies using cells from cystic fibrosis patients or heterologous expression systems have demonstrated that defective Cl- conductance at the cell surface and defective acidification of the Golgi compartment are associated with the presence of mutant forms of CFTR. It is possible that mutation of CFTR could also result in altered Golgi function, consistent with reports of changes in the glycosylation of cell surface and secreted glycoproteins in cystic fibrosis. Glycosylation of cell surface glycoproteins, particularly levels of sialylation, may also be related to the increased binding of Pseudomonas to cystic fibrosis cells. The current study was undertaken to compare the sialylation of cell surface glycoconjugates in heterologous cells overexpressing normal CFTR or Delta F508 CFTR. The presence of sialylated residues on cells was assessed by the surface binding of the specific lectins, wheat germ agglutinin and elderberry bark lectin. A fluorescent cholera toxin B subunit probe was used to measure surface binding to sialylated gangliosides in transfected cells. Our studies show that cells lacking CFTR and cells expressing normal CFTR have unaltered levels of sialylation. In contrast, cells expressing the Delta F508 CFTR have significantly decreased amounts of sialylated glycoproteins and gangliosides on the cell surface. These results suggest that Delta F508 CFTR may perturb intracellular functions, probably at the level of Golgi processing, resulting in the appearance of cell surface asialoglycoconjugates. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT PATHOL & PEDIAT,BOSTON,MA 02129. RP DOSANJH, A (reprint author), MASSACHUSETTS GEN HOSP,JOEY ODONNELL CYST FIBROSIS CTR,RENAL UNIT,BOSTON,MA 02129, USA. NR 32 TC 50 Z9 50 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 FEB PY 1994 VL 266 IS 2 BP C360 EP C366 PN 1 PG 7 WC Physiology SC Physiology GA NA801 UT WOS:A1994NA80100005 PM 7511336 ER PT J AU SCHWARTZ, GJ BROWN, D MANKUS, R ALEXANDER, EA SCHWARTZ, JH AF SCHWARTZ, GJ BROWN, D MANKUS, R ALEXANDER, EA SCHWARTZ, JH TI LOW PH ENHANCES EXPRESSION OF CARBONIC-ANHYDRASE-II BY CULTURED RAT INNER MEDULLARY COLLECTING DUCT CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE RAT; MOUSE; NORTHERN BLOT; REVERSE TRANSCRIPTION; POLYMERASE CHAIN REACTION; KIDNEY; IMMUNOFLUORESCENCE; WESTERN BLOT; BETA-ACTIN; SEQUENCE ID CHRONIC METABOLIC-ACIDOSIS; PHENOL-CHLOROFORM EXTRACTION; GASTRIC PARIETAL-CELLS; RENAL TUBULAR-ACIDOSIS; BRUSH-BORDER VESICLES; SINGLE-STEP METHOD; NUCLEOTIDE-SEQUENCE; CEREBRAL CALCIFICATION; ANTIPORTER ACTIVITY; DEFICIENCY SYNDROME AB Carbonic anhydrase (CA) facilitates the secretion of protons from renal epithelia by catalyzing the buffering of hydroxyl ions by CO2. We have previously found that inner medullary collecting duct (IMCD) cells cultured from rat kidney secrete protons and express CA II. Incubation of IMCD cells in acidic medium for 48 h has been shown to stimulate the secretion of protons by a protein synthesis-dependent process. To establish whether CA II might be involved in this process, IMCD cells were exposed to incubation media supplemented with 10(-7) M deoxycorticosterone acetate, pH 7.0 (acid) or pH 7.7 (control) for 48 h, and CA II mRNA and protein were quantitated. Part of the CA II cDNA was obtained by reverse transcription of total RNA from rat kidney followed by amplification using oligonucleotide primers derived from conserved areas in the coding regions of human, mouse, and chick CA II cDNAs in a polymerase chain reaction. By Northern analysis, steady-state levels of CA II mRNA from acid-incubated cells showed an increase of 80% compared with controls and 70% when expressed relative to a housekeeping mRNA, p-actin. Western blot analysis using a human antibody to CA II showed an approximate doubling of CA II protein after acid incubation. By immunofluorescence microscopy, the domes of acid-incubated IMCD cells contained considerably more CA II-stained cells than found in control cultures. Thus incubation of IMCD cells in acid medium stimulates the expression of CA II mRNA and protein. This upregulation of CA II may be part of the adaptive response to low pH and mag facilitate the increased rate of proton pumping observed under these conditions. C1 UNIV ROCHESTER,MED CTR,DEPT MED,ROCHESTER,NY 14642. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. BOSTON CITY HOSP,THORNDIKE MEM LAB,RENAL SECT,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT MED,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02118. RP SCHWARTZ, GJ (reprint author), UNIV ROCHESTER,MED CTR,DEPT PEDIAT,BOX 77,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NICHD NIH HHS [HD-13232]; NIDDK NIH HHS [DK-42956, DK-28164] NR 49 TC 10 Z9 11 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 FEB PY 1994 VL 266 IS 2 BP C508 EP C514 PN 1 PG 7 WC Physiology SC Physiology GA NA801 UT WOS:A1994NA80100023 PM 8141264 ER PT J AU STUARTTILLEY, A SARDET, C POUYSSEGUR, J SCHWARTZ, MA BROWN, D ALPER, SL AF STUARTTILLEY, A SARDET, C POUYSSEGUR, J SCHWARTZ, MA BROWN, D ALPER, SL TI IMMUNOLOCALIZATION OF ANION-EXCHANGER AE2 AND CATION-EXCHANGER NHE-1 IN DISTINCT ADJACENT CELLS OF GASTRIC-MUCOSA SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE STOMACH; EPITHELIAL POLARITY; ANION EXCHANGER; NHE-1; SODIUM-PROTON EXCHANGER; PROTON-POTASSIUM ION-ADENOSINE-TRIPHOSPHATASE; IMMUNOCYTOCHEMISTRY; IMMUNOBLOT; ACID-BASE ID NA+-H+ EXCHANGER; PARIETAL-CELLS; CARBONIC-ANHYDRASE; CDNA CLONING; BASOLATERAL MEMBRANE; MOLECULAR-CLONING; INTRACELLULAR PH; RABBIT PARIETAL; OXYNTIC CELLS; SURFACE CELLS AB The gastric mucosa secretes both protons and bicarbonate. The molecular identity of the H+-K+-ATPase, which mediates acid secretion, has long been known, but the other components of the secretory machinery and their cellular disposition are less well characterized. This study identifies and localizes in rat and rabbit gastric mucosa a chloride-bicarbonate exchanger protein and a Na+-H+ exchanger protein. The previously described band 3-related protein of the parietal cell has been identified by isoform-specific antibodies as anion exchanger (AE) 2 and localized to the basolateral membranes of the parietal cells. The Na+-H+ exchanger protein NHE-1 was located in the basolateral membranes of the mucous neck cells, interdigitated between the parietal cells of the gastric glands and in the basolateral membranes of the surface mucous cells. Neither transporter protein was abundantly expressed deep in the gland, where most of the pepsinogen cells reside. Carbonic anhydrase II (CA II) was expressed at higher abundance in the surface mucous cells and mucous neck cells, which expressed NHE-1, than in the parietal cells, which expressed AE2. The morphological evidence identified AE2 as a major parietal cell anion exchanger, whereas NHE-1 and CA II colocalized in mucous neck, chief, and surface mucous cells. We propose that all three of these cell types contribute to gastric bicarbonate secretion. C1 BETH ISRAEL HOSP, MOLEC MED UNIT, BOSTON, MA 02215 USA. BETH ISRAEL HOSP, RENAL UNIT, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT CELL BIOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP EAST, RENAL UNIT, BOSTON, MA 02129 USA. SCRIPPS RES INST, COMM VASC BIOL, LA JOLLA, CA 92037 USA. CNRS, CTR BIOCHIM, F-06108 NICE, FRANCE. FU NIDDK NIH HHS [DK-42956, DK-43495] NR 39 TC 118 Z9 119 U1 0 U2 1 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 FEB PY 1994 VL 266 IS 2 BP C559 EP C568 PN 1 PG 10 WC Physiology SC Physiology GA NA801 UT WOS:A1994NA80100030 PM 8141271 ER PT J AU MILLS, I FALLON, JT WRENN, D SASKEN, H GRAY, W BIER, J LEVINE, D BERMAN, S GILSON, M GEWIRTZ, H AF MILLS, I FALLON, JT WRENN, D SASKEN, H GRAY, W BIER, J LEVINE, D BERMAN, S GILSON, M GEWIRTZ, H TI ADAPTIVE RESPONSES OF CORONARY CIRCULATION AND MYOCARDIUM TO CHRONIC REDUCTION IN PERFUSION-PRESSURE AND FLOW SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE HIBERNATION; CORONARY FLOW RESERVE; MICROVESSEL MORPHOMETRY ID SPONTANEOUSLY HYPERTENSIVE RATS; BLOOD-FLOW; ARTERY DISEASE; SKELETAL-MUSCLE; DOMESTIC SWINE; LEFT-VENTRICLE; SMOOTH-MUSCLE; STENOSIS; HYPERTROPHY; DISTAL AB We tested the hypothesis that chronic reduction in perfusion pressure and flow in the coronary circulation induces a state of myocardial ''hibernation'' characterized not only by a steady-state reduction in myocardial O-2 consumption (MVo(2)) but also by evidence of persistent dilator reserve of the distal vasculature. Biochemical and morphological changes in the coronary vasculature were also assessed. Experiments were conducted in swine with an extraluminal coronary stenosis placed 4-32 wk before study. Stenosis reduced lumen diameter by similar to 80% at the time of final experimentation. Baseline, regional myocardial blood flow distal to the stenosis in both endocardial and epicardial layers was reduced vs. that of the normal zone. Vasodilator reserve persisted in both endocardial and epicardial layers of the stenosis zone. Flow increased in each layer in response to adenosine plus phenylephrine and failed to decline despite a marked reduction in perfusion pressure in response to adenosine alone. Regional MVO(2) at baseline was reduced vs. historical controls without coronary stenosis. Protein synthesis rate in coronary vessels of the stenosis zone was reduced vs. that of the normal zone. Morphological responses of stenosis zone vessel walls were heterogeneous. Smaller microvessels exhibited mild hypertrophy of their walls, whereas walls of larger microvessels tended to atrophy. Thus chronic reduction in perfusion pressure and flow induces a state of myocardial hibernation characterized by a steady-state reduction in MVO(2) in association with persistent dilator capacity. Biochemical and morphological changes occur in microvessel walls and may contribute to observed physiological responses. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA 02114. RHODE ISL HOSP,DEPT MED,DIV CARDIOL,PROVIDENCE,RI 02902. BROWN UNIV,RHODE ISL HOSP,SCH MED,DEPT PATHOL,PROVIDENCE,RI 02902. BROWN UNIV,PAWTUCKET MEM HOSP,SCH MED,DEPT PATHOL,PROVIDENCE,RI 02902. FU NHLBI NIH HHS [HL-29951] NR 41 TC 89 Z9 90 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 FEB PY 1994 VL 266 IS 2 BP H447 EP H457 PN 2 PG 11 WC Physiology SC Physiology GA NA803 UT WOS:A1994NA80300013 PM 8141345 ER PT J AU SCHWARTZ, GG GREYSON, CR WISNESKI, JA GARCIA, J STEINMAN, S AF SCHWARTZ, GG GREYSON, CR WISNESKI, JA GARCIA, J STEINMAN, S TI RELATION AMONG REGIONAL O-2 CONSUMPTION, HIGH-ENERGY PHOSPHATES, AND SUBSTRATE UPTAKE IN PORCINE RIGHT VENTRICLE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; ENERGY METABOLISM; CORONARY CIRCULATION; PHOSPHOCREATINE; ADENOSINE 5'-TRIPHOSPHATE; ISOPROTERENOL ID P-31 NMR-SPECTROSCOPY; FREE FATTY-ACIDS; HEART INVIVO; CREATINE-KINASE; MITOCHONDRIAL RESPIRATION; OXYGEN-CONSUMPTION; ATP SYNTHESIS; RAT-HEART; METABOLISM; MYOCARDIUM AB Changes in phosphate metabolites may play a role in the regulation of myocardial oxidative phosphorylation in vivo. We tested the hypothesis that changes in phosphate metabolites with increased myocardial oxygen consumption (MVO(2)) depend on the mechanism by which MVO(2) is increased. In 17 open-chest pigs, regional MVO(2) of the right ventricular (RV) free wall was increased from control by isoproterenol infusion (Iso) and by pulmonary artery constriction (PAC). The phosphocreatine-to-ATP ratio (PCr/ATP), which is inversely related to free ADP concentration ([ADP]), was determined by P-31-nuclear magnetic resonance (NMR) spectroscopy. Regional MVO(2) and lactate, glucose, and free fatty acid (FFA) uptake were determined in the myocardium directly beneath the NMR coil. Iso and PAC increased MVO(2) nearly equally, to approximately twice control, but produced directionally opposite changes in PCr/ATP: a significant decrease with PAC (control 1.52 +/- 0.06, PAC 1.35 +/- 0.06, means +/- SE) but a significant increase with Iso (to 1.72 +/- 0.07). Thus increased [ADP] may have stimulated oxidative phosphorylation during PAC but could not have done so during Iso. With Iso, uptake of FFA was more than three times that with PAC, and the sum of the oxygen extraction ratios for lactate, glucose, and FFA was more than double that with PAC. Enhanced substrate uptake during Iso may have increased mitochondrial NADH, which in turn may have provided an alternative stimulus to the rate of oxidative phosphorylation. These results support multifactorial control of RV oxidative phosphorylation in vivo. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94121. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94121. RP SCHWARTZ, GG (reprint author), SAN FRANCISCO VET AFFAIRS MED CTR,CARDIOL SECT 111C,4150 CLEMENT ST,SAN FRANCISCO,CA 94121, USA. FU NHLBI NIH HHS [HL-02155, HL-07192] NR 37 TC 16 Z9 16 U1 2 U2 2 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 FEB PY 1994 VL 266 IS 2 BP H521 EP H530 PN 2 PG 10 WC Physiology SC Physiology GA NA803 UT WOS:A1994NA80300022 PM 8141353 ER PT J AU JENKINSON, SG LAWRENCE, RA ZAMORA, CA DENEKE, SM AF JENKINSON, SG LAWRENCE, RA ZAMORA, CA DENEKE, SM TI INDUCTION OF INTRACELLULAR GLUTATHIONE IN ALVEOLAR TYPE-II PNEUMOCYTES FOLLOWING BCNU EXPOSURE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE N,N'-BIS(2-CHLOROETHYL)-N-NITROSOUREA; CYSTINE TRANSPORT; OXYGEN TOXICITY ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CYSTINE TRANSPORT ACTIVITY; GLUTAMIC-ACID UPTAKE; ENDOTHELIAL-CELLS; DIETHYL MALEATE; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA BCNU; ELECTROPHILIC AGENTS; HUMAN-FIBROBLASTS; EPITHELIAL-CELLS; RAT HEPATOCYTES AB N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU) is a potent inhibitor of glutathione reductase (GSSG-Red) activity in both tissues and cells. We examined the effects of treating alveolar type II cells with BCNU and found that a marked decrease in cellular GSSG-Red activity occurred in these cells associated with a time-dependent increase in cellular glutathione (GSH) concentrations. The increase in GSH was not found to be related to changes in cellular gamma-glutamyl transpeptidase activity, gamma-glutamylcysteine synthetase activity, nor increased intracellular transport of cystine. When the BCNU-exposed cells were incubated with hydrogen peroxide to produce oxidant stress, the cells exhibited increased susceptibility to oxidant damage when compared with controls, despite the fact that cellular concentrations of GSH were markedly elevated. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE MED,SAN ANTONIO,TX 78284. RP JENKINSON, SG (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,PULM DIS SECT 111E,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU NHLBI NIH HHS [HL-30556, HL-32824] NR 41 TC 19 Z9 19 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 FEB PY 1994 VL 266 IS 2 BP L125 EP L130 PN 1 PG 6 WC Physiology SC Physiology GA NA801 UT WOS:A1994NA80100072 PM 7908172 ER PT J AU MCKAY, JR ALTERMAN, AI MCLELLAN, AT SNIDER, EC AF MCKAY, JR ALTERMAN, AI MCLELLAN, AT SNIDER, EC TI TREATMENT GOALS, CONTINUITY OF CARE, AND OUTCOME IN A DAY HOSPITAL SUBSTANCE-ABUSE REHABILITATION PROGRAM SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ADDICTION SEVERITY INDEX; DRUG-ABUSE; ALCOHOLISM AB Objective: Relationships between day hospital treatment goals, self-help group participation, and substance use outcome were examined for 180 alcohol- or cocaine-dependent male patients in a day hospital Veterans Administration substance abuse program. Method: The primary goals assessed were completion of the day hospital program and participation in posttreatment self-help groups. For subjects who completed the day hospital program, progress toward three other goals was also assessed: decreased denial, endorsement of 12-Step beliefs, and participation in self-help groups during the day hospital program. The outcome measures were urine toxicology and self-reports of alcohol or cocaine use at 4- and 7-month post-intake follow-up interviews. Results: Day hospital completion and participation in posttreatment self-help groups predicted better outcome. Self-help participation also predicted outcome after day hospital completion was controlled. Among subjects who completed the day hospital program, the other three goals did not predict substance use outcome. However, involvement with self-help groups during the day hospital program and decreases in denial Predicted continued involvement with self-help groups. Conclusions: Patients who complete day hospital substance abuse rehabilitation and then continue to participate in self-help groups are likely to have lower rates of alcohol and cocaine use during follow-up. Furthermore, the beneficial effect of self-help group participation does not appear to be strictly the result of motivation or some other patient characteristic. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP MCKAY, JR (reprint author), UNIV PENN,SCH MED,DEPT PSYCHIAT,TREATMENT RES CTR,3900 CHESTNUT ST,PHILADELPHIA,PA 19104, USA. FU NIDA NIH HHS [DA-05186] NR 21 TC 93 Z9 93 U1 1 U2 5 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 FEB PY 1994 VL 151 IS 2 BP 254 EP 259 PG 6 WC Psychiatry SC Psychiatry GA MV488 UT WOS:A1994MV48800018 PM 8296899 ER PT J AU ROSE, RM CATALANO, PJ KOZIEL, H FURLONG, ST AF ROSE, RM CATALANO, PJ KOZIEL, H FURLONG, ST TI ABNORMAL LIPID-COMPOSITION OF BRONCHOALVEOLAR LAVAGE FLUID OBTAINED FROM INDIVIDUALS WITH AIDS-RELATED LUNG-DISEASE SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED IMMUNODEFICIENCY SYNDROME; MACROPHAGE MANNOSE RECEPTOR; PULMONARY SURFACTANT; COLORIMETRIC DETERMINATION; PHOSPHOLIPID PROFILE; RAT; ATTACHMENT; MECHANISM; VOLUME AB Surfactant lipids are not only important to the physiologic function of the lungs, but may also influence disease processes like Pneumocystis pneumonia, in which the interaction of host-defense cells with pathogen occurs within the confines of the surfactant-rich alveolar hypophase. In the present studies the lipid profile of bronchoalveolar lavage fluid (BALF) was characterized in subjects with AIDS-related lung diseases including Pneumocystis pneumonia. BALF lipid and total protein measurements were made in 43 subjects with acquired immune deficiency syndrome (AIDS)-related lung disease and compared with those made in 50 normal human immunodeficiency virus (HIV)-seronegative controls. The AIDS patient samples contained significantly greater amounts of total cholesterol, phosphatidylglycerol (PG), and protein than the control samples; in contrast to previous observations in rodent P. carinii infection, no differences were seen in total phospholipid (PL) or phosphatidylcholine (PC) in the two groups. The proportions of several of these lipids were deranged in BALF obtained from the patient group: PG/PL and PC/cholesterol differed significantly from normal samples. In the subset of patients with AIDS-related Pneumocystis pneumonia, no correlation was apparent between discrete BALF lipids and clinical indices reflective of disease severity. Using these measurements to approximate the lipid composition of the alveolar microenvironment in AIDS-related lung disease, we performed experiments in which normal human alveolar macrophages were exposed to exogenous liposomal lipids and then challenged with P. carinii. The ingestion but not binding of P. carinii by macrophages was diminished as a result of lipid exposure. These studies document a unique abnormality in BALF lipids that may have an important impact on the pathobiology of AIDS-related lung disease. C1 NEW ENGLAND DEACONESS HOSP,DIV PULM & CRIT CARE MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA. FU NHLBI NIH HHS [HL43510] NR 37 TC 19 Z9 19 U1 1 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB PY 1994 VL 149 IS 2 BP 332 EP 338 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NP718 UT WOS:A1994NP71800011 PM 8306026 ER PT J AU SHAFFER, K ROSADODECHRISTENSON, ML PATZ, EF YOUNG, S FARVER, CF AF SHAFFER, K ROSADODECHRISTENSON, ML PATZ, EF YOUNG, S FARVER, CF TI THORACIC LYMPHANGIOMA IN ADULTS - CT AND MR-IMAGING FEATURES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CYSTIC LYMPHANGIOMA; DIAGNOSIS; MASS; MEDIASTINUM; HYGROMAS; CHILDREN AB OBJECTIVE. Lymphangiomas are rare benign tumors most often seen in childhood. When they occur in adults, radiologic diagnosis can be difficult. A retrospective study of the CT and MR appearances of thoracic lymphangiomas in adult patients was performed in order to describe the range of radiologic features of these tumors. MATERIALS AND METHODS. Cases of adult lymphangioma at three institutions were identified in the records of 19 patients, predominantly female, 18-67 years old. RESULTS. The most common CT appearance was a smoothly marginated cystic mass. Unusual features included calcification, spiculated margins, and homogeneous soft-tissue attenuation. The majority of cases were located in the anterior or superior mediastinum. Unusual locations included the pericardium, pulmonary hilum, and pulmonary parenchyma. Signal characteristics on MR images varied. CONCLUSION. The radiographic appearance of lymphangiomas in the chest in adult patients is varied. The diagnosis cannot be suggested on the basis of radiologic studies alone. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT RADIOL & NUCL MED,BETHESDA,MD 20814. ARMED FORCES INST PATHOL,DEPT RADIOL PATHOL,WASHINGTON,DC 20306. DUKE UNIV,DEPT RADIOL,DURHAM,NC 27710. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RP SHAFFER, K (reprint author), DANA FARBER CANC INST,DEPT RADIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 38 TC 52 Z9 58 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 1994 VL 162 IS 2 BP 283 EP 289 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MU880 UT WOS:A1994MU88000005 PM 8310910 ER PT J AU KOPANS, DB AF KOPANS, DB TI CONVENTIONAL WISDOM - OBSERVATION, EXPERIENCE, ANECDOTE, AND SCIENCE IN BREAST IMAGING SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID PARENCHYMAL PATTERNS; CANCER; MAMMOGRAPHY; DENSITY; RISK; AGE AB Science is and should be the foundation of modern medicine, but observation and experience remain key elements in day-to-day clinical care. As mammography and other breast imaging techniques have evolved, early impressions have been replaced by more rigorous scientific testing, which has led to a more thorough understanding of the breast and the anatomic and morphologic origins of the imaging observations. As is true in many reports that involve the use of a new technique, early information is observational and anecdotal and frequently lacking the all-important ''denominator'' for a particular observation. For a ''sign'' to be accepted as a reliable indicator of a process, its associations must be compared with the overall prevalence of the observation in the healthy population. Observed associations must be corroborated by objective analysis. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. NR 15 TC 21 Z9 21 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X EI 1546-3141 J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 1994 VL 162 IS 2 BP 299 EP 303 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MU880 UT WOS:A1994MU88000009 PM 8310914 ER PT J AU GERVAIS, DA WHITMAN, GJ AF GERVAIS, DA WHITMAN, GJ TI EMPHYSEMATOUS PYELONEPHRITIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP GERVAIS, DA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 8 Z9 9 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 1994 VL 162 IS 2 BP 348 EP 348 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MU880 UT WOS:A1994MU88000019 PM 8310924 ER PT J AU COTE, CJ FERRARI, LR LIU, LMP AF COTE, CJ FERRARI, LR LIU, LMP TI RECTAL METHOHEXITAL FOR SEDATION OF CHILDREN DURING IMAGING PROCEDURES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Letter ID PEDIATRIC-PATIENTS RP COTE, CJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 8 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 FEB PY 1994 VL 162 IS 2 BP 465 EP 466 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MU880 UT WOS:A1994MU88000050 PM 8310952 ER PT J AU ACKERMAN, RH AF ACKERMAN, RH TI ECONOMIC AND MEDICAL DIRECTIONS IN THE CZECH-REPUBLIC AND HUNGARY SO AMERICAN JOURNAL OF SURGERY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. RP ACKERMAN, RH (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,NEUROVASC LAB,BOSTON,MA 02114, USA. NR 0 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 0002-9610 J9 AM J SURG JI Am. J. Surg. PD FEB PY 1994 VL 167 IS 2 BP 246 EP 249 DI 10.1016/0002-9610(94)90085-X PG 4 WC Surgery SC Surgery GA MY223 UT WOS:A1994MY22300008 PM 8135313 ER PT J AU FAHMY, NR SUNDER, N PATEL, D AF FAHMY, NR SUNDER, N PATEL, D TI THE PNEUMATIC TOURNIQUET CAN BE HAZARDOUS IN PATIENTS WITH CORONARY-ARTERY DISEASE SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ORTHOPAED SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1994 VL 78 IS 2 SU S BP U66 EP U66 PG 1 WC Anesthesiology SC Anesthesiology GA NA406 UT WOS:A1994NA40600104 ER PT J AU GOUDSOUZIAN, NG AF GOUDSOUZIAN, NG TI MIVACURIUM INFUSION REQUIREMENTS FOLLOWING AN INTUBATING DOSE OF ATRACURIUM OR VECURONIUM IN CHILDREN SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1994 VL 78 IS 2 SU S BP U81 EP U81 PG 1 WC Anesthesiology SC Anesthesiology GA NA406 UT WOS:A1994NA40600133 ER PT J AU KAUFMANN, M STEINER, LA DROP, LJ CASTELLI, I SCHOUTEN, PHR WELCH, CA DAGOSTINO, R ZASLAVSKY, A ALFILLE, PH AF KAUFMANN, M STEINER, LA DROP, LJ CASTELLI, I SCHOUTEN, PHR WELCH, CA DAGOSTINO, R ZASLAVSKY, A ALFILLE, PH TI COMPARATIVE RESPONSES TO ESMOLOL AND LABETALOL DURING ELECTROCONVULSIVE-THERAPY SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. KANTONSSPITAL,DEPT ANASTHESIA,CH-4031 BASEL,SWITZERLAND. 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 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1994 VL 78 IS 2 SU S BP U112 EP U112 PG 1 WC Anesthesiology SC Anesthesiology GA NA406 UT WOS:A1994NA40600195 ER PT J AU TAGLIENTE, TM AF TAGLIENTE, TM TI HALOTHANE-INDUCED ALTERATIONS IN RAT-BRAIN NITRIC-OXIDE SYNTHASE ACTIVITY ARE CONCENTRATION AND REGION DEPENDENT SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 MT SINAI SCH MED,NEW YORK,NY. BRONX VET ADM MED CTR,NEW YORK,NY. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 1994 VL 78 IS 2 SU S BP U225 EP U225 PG 1 WC Anesthesiology SC Anesthesiology GA NA406 UT WOS:A1994NA40600420 ER PT J AU GOTO, T MAROTA, JJA CROSBY, G AF GOTO, T MAROTA, JJA CROSBY, G TI NITROUS-OXIDE INDUCES PREEMPTIVE ANALGESIA IN THE RAT THAT IS ANTAGONIZED BY HALOTHANE SO ANESTHESIOLOGY LA English DT Article DE ANALGESIA, PREEMPTIVE; ANESTHESIA, GENERAL; ANESTHETICS, GASES, NITROUS OXIDE; ANESTHETICS, VOLATILE, HALOTHANE; PAIN, NEUROPLASTICITY; SENSITIZATION ID FORMALIN TEST; ANESTHETIC REQUIREMENT; NALOXONE; PAIN; HYPERALGESIA; MORPHINE; REVERSAL; NEURONS; SYSTEM; INPUT AB Background: Noxious stimulation-induced sensitization of the central nervous system has been proposed as a key element in the development of subsequent protracted pain. Accordingly, the authors used the formalin model of pain to test the hypothesis that general anesthesia can produce preemptive analgesia and thereby interfere with noxious stimulation-induced central sensitization. Methods: Rats received 0.9% or 1.8% halothane, 30% or 75% nitrous oxide (N2O), or 75% N2O plus 0.9% halothane (n = 4 or 5 per group). Control rats (n = 5) received only 100% oxygen. Fifteen minutes after the induction of anesthesia, formalin was injected subcutaneously into a hind paw of each rat, and anesthesia was maintained for 5 more min. Because the behavioral pain response to formalin (i.e., flinching of the injected paw) is biphasic, these treatment groups were anesthetized only during phase 1 (acute phase). Another group (n = 5) received 75% N2O only during phase 2 (delayed phase). Reversibility of the N2O effect was tested by the administration of naloxone before phase 1 or naltrexone during phase 2 (n = 5 per group). Finally, additional rats anesthetized as described above (n = 4 or 5 per group) underwent tail-hick testing during anesthesia. Results: All anesthetics reduced phase 1 pain behavior, but only N2O produced antinociception on tail-flick testing. Thirty percent and 75% N2O, administered during phase 1, suppressed phase 2 flinching 29% and 49%, respectively, whereas nitrous oxide administered after phase 1 did not suppress phase 2 pain behavior. This effect of nitrous oxide was reversed by an opioid antagonist given during phase 1 but not phase 2. Halothane administered during phase I had no effect on phase 2 flinching, and it antagonized the effect of 75% N2O. Conclusions: Nitrous oxide induces dose-dependent preemptive analgesia in this model that is reversed partially by naloxone, thus suggesting the involvement of endogenous opioids in this action. In contrast, halothane has no preemptive analgesic properties and even antagonizes the analgesic effect of nitrous oxide. Hence, the hypnotic potency of an anesthetic is a poor indication of its preemptive analgesic potential. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,ANESTHESIA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02115. FU NIGMS NIH HHS [R01 GM42466] NR 35 TC 72 Z9 72 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD FEB PY 1994 VL 80 IS 2 BP 409 EP 416 DI 10.1097/00000542-199402000-00021 PG 8 WC Anesthesiology SC Anesthesiology GA MX446 UT WOS:A1994MX44600020 PM 8311323 ER PT J AU ALLES, AJ WARSHAW, AL SOUTHERN, JF COMPTON, CC LEWANDROWSKI, KB AF ALLES, AJ WARSHAW, AL SOUTHERN, JF COMPTON, CC LEWANDROWSKI, KB TI EXPRESSION OF CA-72-4 (TAG-72) IN THE FLUID CONTENTS OF PANCREATIC CYSTS - A NEW MARKER TO DISTINGUISH MALIGNANT PANCREATIC CYSTIC TUMORS FROM BENIGN NEOPLASMS AND PSEUDOCYSTS SO ANNALS OF SURGERY LA English DT Article ID CARCINOEMBRYONIC ANTIGEN; CYSTADENOCARCINOMA; CYSTADENOMA; DIAGNOSIS; LESIONS AB Objective The authors evaluated cyst fluid CA 72-4 as a tumor marker in the differential diagnosis of pancreatic cystic lesions. Summary Background Data Pancreatic cystic lesions include inflammatory pseudocysts, serous cystadenomas, and mucinous tumors. Mucinous tumors can be further subdivided into mucinous cystadenocarcinomas and premalignant mucinous cystic neoplasms. The clinical and radiologic features of these lesions are unreliable to make a preoperative diagnosis of these diagnostically difficult lesions. Analysis of aspirated cyst fluid was Proposed as an aid to making the preoperative differential diagnosis. Currently, a number of parameters have been reported as useful markers in cyst fluid aspirates, including the tumor markers carcinoembryonic antigen and CA 15.3, enzymes (amylase, lipase, and amylase isoenzymes), relative viscosity, and cytologic analysis. However, owing to the rarity of pancreatic cystic tumors, experience with cyst fluid analysis is limited. To define additional markers that might be useful in the differential diagnosis of pancreatic cysts, the authors measured the tumor-associated glycoprotein 72 (TAG-72) in aspirates from 19 pancreatic cystic lesions. Methods Cyst fluid from 19 pancreatic cysts was obtained by needle aspiration. The tumor marker TAG72 was measured by a commercial (CA 72-4) immunoassay. Results Cyst fluid CA 72-4 levels in mucinous cystadenocarcinomas were markedly elevated (mean, 10,027 U/mL; range, 780 to 34,853 U/mL) compared with that in pseudocysts (mean, 3.8 U/mL; range, < 3 to 5.7 U/mL) and serous cystadenomas (mean and range, < 3 U/mL; p < 0.001). The level of CA 72-4 in benign mucinous cystic neoplasms was intermediate (mean, 44.2 U/mL; range, < 3 to 137 U/mL), but it was statistically different from either carcinomas (p = 0.009) or benign cysts (p < 0.001). Conclusions CA 72-4 in cyst fluid aspirates is a promising new marker for the differentiation of mucinous cystadenocarcinoma from pseudocysts, serous cystadenomas, and mucinous cystic neoplasms. Intermediate values are associated with benign mucinous cystic neoplasms. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP ALLES, AJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 18 TC 64 Z9 66 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 FEB PY 1994 VL 219 IS 2 BP 131 EP 134 DI 10.1097/00000658-199402000-00004 PG 4 WC Surgery SC Surgery GA MW852 UT WOS:A1994MW85200004 PM 8129483 ER PT J AU SINGER, S CORSON, JM GONIN, R LABOW, B EBERLEIN, TJ AF SINGER, S CORSON, JM GONIN, R LABOW, B EBERLEIN, TJ TI PROGNOSTIC FACTORS PREDICTIVE OF SURVIVAL AND LOCAL RECURRENCE FOR EXTREMITY SOFT-TISSUE SARCOMA SO ANNALS OF SURGERY LA English DT Article ID LIMB-SPARING SURGERY; ADJUVANT CHEMOTHERAPY; RANDOMIZED TRIAL; RADIATION-THERAPY; GROUP EXPERIENCE; DOXORUBICIN AB Objective The authors sought to identify prognostic factors in the management of extremity soft tissue sarcoma. Summary Background Data The surgical management of soft tissue sarcoma has evolved because of advances in therapy, resulting in increased limb preservation and quality of life. However, identifying a subset of patients most likely to benefit from adjuvant chemotherapy has been difficult to achieve. Methods A retrospective analysis of a prospective data base of 182 patients with extremity sarcomas from 1970 to 1992 was performed. Results A histologic diagnosis of Ewing's sarcoma, synovial sarcoma, and angiosarcoma was associated with 13-fold increased risk of death compared with liposarcoma, fibrosarcoma, and malignant peripheral nerve sheath histologic types after having adjusted for the other prognostic factors (p < 0.001). In addition to histologic type, high-grade sarcomas (p = 0.018), sarcomas greater than 10 cm in size (p = 0.006), and age at diagnosis (p = 0.016) were found to be important prognostic factors for survival but not for local recurrence. For the first time to their knowledge, the authors showed that mean mitotic activity has prognostic value after having adjusted for other prognostic factors, such as grade (p = 0.005). The only prognostic factors predictive for local recurrence were whether the patient presented with locally recurrent disease (p = 0.0001) or had microscopically positive margins (p = 0.052). Conclusions The use of mitotic activity along with grade, size, histologic type, and age al diagnosis is prognostic for survival in extremity soft tissue sarcoma. The use of an objective pathologic feature, such as mean mitotic activity, is also useful in selecting patients for future systemic neoadjuvant or adjuvant trials and primary therapy. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. RP SINGER, S (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT SURG,DIV SURG ONCOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 28 TC 148 Z9 151 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD FEB PY 1994 VL 219 IS 2 BP 165 EP 173 DI 10.1097/00000658-199402000-00008 PG 9 WC Surgery SC Surgery GA MW852 UT WOS:A1994MW85200008 PM 8129487 ER PT J AU ALSTON, TA DAMBRA, MN AF ALSTON, TA DAMBRA, MN TI APROTININ DOES NOT NEUTRALIZE HEPARIN SO ANNALS OF THORACIC SURGERY LA English DT Letter RP ALSTON, TA (reprint author), MASSACHUSETTS GEN HOSP,HARVARD MED SCH,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 5 TC 1 Z9 1 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 FEB PY 1994 VL 57 IS 2 BP 516 EP 516 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA MX450 UT WOS:A1994MX45000054 PM 7508714 ER PT J AU PUSKAS, JD MATHISEN, DJ AF PUSKAS, JD MATHISEN, DJ TI PULMONARY ARTERIOVENOUS-MALFORMATIONS - OPTIONS FOR MANAGEMENT - REPLY SO ANNALS OF THORACIC SURGERY LA English DT Letter RP PUSKAS, JD (reprint author), MASSACHUSETTS GEN HOSP,THORAC SURG SERV,WARREN 11TH FLOOR,BOSTON,MA 02114, USA. NR 0 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 1994 VL 57 IS 2 BP 521 EP 521 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA MX450 UT WOS:A1994MX45000060 ER PT J AU PEFANIS, A THAUVINELIOPOULOS, C HOLDEN, J ELIOPOULOS, GM FERRARO, MJ MOELLERING, RC AF PEFANIS, A THAUVINELIOPOULOS, C HOLDEN, J ELIOPOULOS, GM FERRARO, MJ MOELLERING, RC TI ACTIVITY OF FLEROXACIN ALONE AND IN COMBINATION WITH CLINDAMYCIN OR METRONIDAZOLE IN EXPERIMENTAL INTRAABDOMINAL ABSCESSES SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COMPARATIVE INVITRO ACTIVITY; THERAPEUTIC EFFICACY; EXPERIMENTAL-MODEL; RO-23-6240; RATS; PHARMACOKINETICS; 4-QUINOLONE; QUINOLONE; SEPSIS AB To assess the potential efficacy of fleroxacin in combination with clindamycin or metronidazole in mixed aerobic and anaerobic infections, we used a rat model of intra-abdominal abscesses in which the inoculum consisted of pooled rat feces mixed with BaSO4. Two hours after bacterial challenge, antimicrobial therapy was begun intravenously with regimens designed to simulate human pharmacokinetics. A combination of clindamycin and gentamicin was included as an established treatment regimen. After 8.5 days of therapy, final bacterial counts in abscesses showed that fleroxacin alone or combined with metronidazole or clindamycin effectively eradicated Escherichia coli, with bacterial densities of less than or equal to 2.84 +/- 0.1, less than or equal to 2.9 +/- 0.1, and less than or equal to 2.95 +/- 0.1 (mean +/- standard error of the mean) log(10) CFU/g, respectively. The addition of either clindamycin or metronidazole to fleroxacin substantially enhanced the effectiveness of the regimens against Bacteroides fragilis, with bacterial counts of less than or equal to 3.0 +/- 0.1 or less than or equal to 2.9 +/- 0.1 log(10) CFU/g, respectively, versus 9.2 +/- 0.2 log(10) CFU/g for fleroxacin alone. The combination of metronidazole and fleroxacin also resulted in a significantly greater reduction of peptostreptococci and Bacteroides thetaiotaomicron than fleroxacin alone (less than or equal to 2.9 +/- 0.1 versus 6.1 +/- 0.9 log(10) CFU/g and 3.3 +/- 0.4 versus 8.3 +/- 0.1 log(10) CFU/g, respectively). Except for those of B. fragilis, counts of other anaerobes were reduced to a greater extent by metronidazole plus fleroxacin than by clindamycin plus fleroxacin, although differences were not always significant. Metronidazole plus fleroxacin was at least as active as clindamycin plus gentamicin against all species and was significantly more active against Clostridium spp. No regimen effectively eradicated enterococci from the abscesses. These results suggest that the addition of either metronidazole or clindamycin would effectively enhance the spectrum of fleroxacin for treatment of mixed aerobic and anaerobic infections. C1 NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT MICROBIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 17 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 1994 VL 38 IS 2 BP 252 EP 255 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA MU932 UT WOS:A1994MU93200018 PM 8192453 ER PT J AU ZHANG, D CALIENDO, AM ERON, JJ DEVORE, KM KAPLAN, JC HIRSCH, MS DAQUILA, RT AF ZHANG, D CALIENDO, AM ERON, JJ DEVORE, KM KAPLAN, JC HIRSCH, MS DAQUILA, RT TI RESISTANCE TO 2',3'-DIDEOXYCYTIDINE CONFERRED BY A MUTATION IN CODON-65 OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID POLYMERASE CHAIN-REACTION; URACIL DNA GLYCOSYLASE; HIGH-LEVEL RESISTANCE; ZIDOVUDINE; MUTAGENESIS; INVITRO; CULTURE; 3'-AZIDO-3'-DEOXYTHYMIDINE; INHIBITORS; CLONING AB A human immunodeficiency virus type 1 variant resistant to zalcitabine (2',3'-dideoxycytidine [ddC]) was selected by sequential passage in the presence of increasing concentrations of ddC in peripheral blood mononuclear cell cultures. A mutation causing a lysine-to-arginine substitution was noted in reverse transcriptase (RT) codon 65 of this ddC-selected virus. A cloned mutant virus with this codon 65 mutation was constructed by using a novel PCR approach for site-directed mutagenesis. Characterization of this virus confirmed that the RT Lys-65-->Arg substitution was necessary and sufficient for a fourfold increase in the ddC 50% inhibitory concentration, as well as for resistance to didanosine (2',3'-dideoxyinosine [ddI]). Lys-G-->Arg and virus resistance to ddC and ddI also developed during therapy in isolates from one ddC-treated patient and two ddI-treated patients. Recombinant-expressed codon 65 mutant RT enzyme was resistant to ddCTP and ddATP in cell-free polymerase assays. Results of mutant enzyme studies are consistent with Lys-65-->Arg leading to changes in binding of the triphosphate forms of these nucleoside analogs to the RT. These data have implications for future studies of ddC resistance, particularly those aimed at defining its clinical relevance. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU FIC NIH HHS [D43 TW00004]; NCI NIH HHS [CA12464]; NIAID NIH HHS [AI 29193] NR 35 TC 123 Z9 126 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 1994 VL 38 IS 2 BP 282 EP 287 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA MU932 UT WOS:A1994MU93200023 PM 7514856 ER PT J AU ARNOLD, SE HYMAN, BT VANHOESEN, GW AF ARNOLD, SE HYMAN, BT VANHOESEN, GW TI NEUROPATHOLOGIC CHANGES OF THE TEMPORAL POLE IN ALZHEIMERS-DISEASE AND PICKS-DISEASE SO ARCHIVES OF NEUROLOGY LA English DT Article ID RHESUS-MONKEY; NEUROFIBRILLARY TANGLES; SENILE PLAQUES; AFFERENT CONNECTIONS; PROGRESSIVE APHASIA; NEURAL INPUTS; LAMINAR; CORTEX; DISTRIBUTIONS; PRIMATES AB Objective: To describe the pattern of neuropathologic changes in temporal polar cortex in Alzheimer's disease (AD) in comparison with changes in Pick's disease (PD) and normal elderly cytoarchitecture. Design: Examination of degenerative changes, neurofibrillary tangles, and senile plaques in the temporal poles of 10 patients with AD, three patients with PD, and five age-compatible control subjects, by means of thionin and thioflavine S stains and Alz-50 and ubiquitin immunocytochemistry. Subjects: All patients had a documented history of dementia and AD or PD confirmed on neuropathologic examination. Control subjects were without a history of cognitive impairment or evident neuropathologic changes. Outcome Measures: Cytoarchitecture, neuronal loss, neurofibrillary tangles, senile plaques, and Pick bodies. Results: All patients with AD showed atrophy of the temporal pole and marked neuronal loss, especially in layers III and V and, to a lesser degree, in layers II and VI. Heavy accumulation of neurofibrillary tangles was found in layers II, III, V, and VI. Patients with PD showed extensive neuron loss throughout, although this appeared to be most prominent in layer III. Conclusions: Both AD and PD pathologic changes severely affect the layers of the temporal pole that mediate widespread reciprocal connections with temporal and frontal cortices and limbic cortical and subcortical structures. Neural systems that interconnect temporal polar cortex with sensory association areas and memory-related limbic structures are, therefore, disrupted, and it is likely that these lesions play a role in the multifaceted cognitive and behavioral changes of AD and PD. C1 UNIV PENN,DEPT NEUROL,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. UNIV IOWA,DEPT ANAT,IOWA CITY,IA 52242. UNIV IOWA,DEPT NEUROL,IOWA CITY,IA 52242. RP ARNOLD, SE (reprint author), UNIV PENN,DEPT PSYCHIAT,DIV NEUROPSYCHIAT,10 GATES BLDG,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. RI Arnold, Steven/J-7546-2012 FU NIA NIH HHS [AG08487]; NINDS NIH HHS [NS14911]; PHS HHS [P019632] NR 51 TC 50 Z9 50 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 1994 VL 51 IS 2 BP 145 EP 150 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA MW625 UT WOS:A1994MW62500008 PM 8304839 ER PT J AU SEDDON, JM HENNEKENS, CH AF SEDDON, JM HENNEKENS, CH TI VITAMINS, MINERALS, AND MACULAR DEGENERATION - PROMISING BUT UNPROVED HYPOTHESES SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID RETINAL-PIGMENT EPITHELIUM; ZINC; ASCORBATE; LIGHT; RATS RP SEDDON, JM (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EPIDEMIOL UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. NR 24 TC 26 Z9 27 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 1994 VL 112 IS 2 BP 176 EP 179 PG 4 WC Ophthalmology SC Ophthalmology GA MV882 UT WOS:A1994MV88200017 PM 8311768 ER PT J AU NELSON, S PRITT, A MARLAR, RA AF NELSON, S PRITT, A MARLAR, RA TI RAPID PREPARATION OF PLASMA FOR STAT COAGULATION-TESTING SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article AB We undertook to confirm and extend the previous work on the use of microcentrifugation (2 minutes at 11000g) to prepare platelet-poor plasma for assay of the prothrombin time, partial thromboplastin time, fibrinogen level, D-dimer, antithrombin Ill, and dilute Russell viper venom time. We compared results of routinely submitted blood samples by both high-speed and routine (15 minutes at 1800g) centrifugation. We found no significant differences in assay results and concluded that the high-speed technique is a reliable and useful option for minimizing turnaround times for these coagulation assays. C1 UNIV COLORADO,HLTH SCI CTR,DENVER VET AFFAIRS MED CTR,LAB SERV 113,DENVER,CO 80220. NR 4 TC 13 Z9 14 U1 0 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 1994 VL 118 IS 2 BP 175 EP 176 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA MV289 UT WOS:A1994MV28900020 PM 8311659 ER PT J AU HEISLEIN, DM HARRIS, BA JETTE, AM AF HEISLEIN, DM HARRIS, BA JETTE, AM TI A STRENGTH TRAINING-PROGRAM FOR POSTMENOPAUSAL WOMEN - A PILOT-STUDY SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID QUADRICEPS MUSCLE STRENGTH; BONE-LOADING EXERCISES; CONNECTIVE-TISSUE; SKELETAL-MUSCLE; MINERAL DENSITY; ELDERLY MEN; MORPHOLOGY; AGE; OSTEOPOROSIS; HYPERTROPHY C1 MASSACHUSETTS GEN HOSP,ORTHOPAED ONCOL SERV,BOSTON,MA 02114. NEW ENGLAND RES INST,BOSTON,MA. MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,GRAD PROGRAM PHYS THERAPY,BOSTON,MA 02114. RP HEISLEIN, DM (reprint author), MASSACHUSETTS GEN HOSP,DEPT PHYS THERAPY,PHYS THERAPY SERV,WACC 128,55 FRUIT ST,BOSTON,MA 02114, USA. NR 56 TC 25 Z9 25 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD FEB PY 1994 VL 75 IS 2 BP 198 EP 204 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA MW994 UT WOS:A1994MW99400013 PM 8311678 ER PT J AU LORSCH, JR SZOSTAK, JW AF LORSCH, JR SZOSTAK, JW TI IN-VITRO SELECTION OF RNA APTAMERS SPECIFIC FOR CYANOCOBALAMIN SO BIOCHEMISTRY LA English DT Article ID STRANDED-DNA MOLECULES; RIBOSOMAL-RNA; RECOGNITION; BINDING; ENZYME AB RNA receptors (aptamers) capable of specifically binding cyanocobalamin (vitamin B12) have been isolated by in vitro selection from a pool of 5 X 10(14) RNAs of random sequence. After eight rounds of selection by affinity chromatography and enzymatic amplification, the pool was dominated by two sequences. The major sequence, comprising 60% of the pool, was studied further. It was found to bind vitamin B-12 in solution with a dissociation constant (K(d)) of approximately 320 +/- 90 nM and to bind cobinamide dicyanide with a K(d) of 8.8 +/- 0.5 muM. The aptamer does not detectably bind adenosylcobalamin (coenzyme B-12). The selection was conducted in 1 M LiCl, and binding is dependent on the presence of high concentrations of Li+ but independent of Mg2+. To define the binding site for cyanocobalamin, a second cyanocobalamin-binding selection was carried out using a pool of sequences derived from the major aptamer sequence randomized at a level of 30%. The sequence data from this selection revealed a 31-base highly conserved region, on the basis of which was synthesized a smaller aptamer of 35 nucleotides. This small aptamer binds cyanocobalamin in solution with a K(d) of 88 +/- 19 nM and cobinamide dicyanide with a K(d) of 20 +/- 9 muM. This aptamer has the highest affinity yet reported for a small molecule ligand. A number of covarying positions were found in the conserved region of the sequences from this second, mutagenized pool selection. On the basis of these data, an unusual pseudoknot secondary structure is proposed for the aptamer. Chemical modification protection experiments are consistent with this structure and have demonstrated that the RNA undergoes a conformational change upon binding its ligand. Possible contacts with the cyanocobalamin have also been mapped. A third selection was carried out in which the salt specificity of the aptamer was changed from LiCl to NaCl plus MgCl2. Sequence analysis of the final round pool of RNAs from this selection revealed several conserved changes from the original vitamin B-12 aptamer sequence. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. OI Lorsch, Jon/0000-0002-4521-4999 NR 35 TC 155 Z9 156 U1 4 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 1 PY 1994 VL 33 IS 4 BP 973 EP 982 DI 10.1021/bi00170a016 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MU988 UT WOS:A1994MU98800016 PM 7508262 ER PT J AU ROSS, RJ BALL, WA DINGES, DF KRIBBS, NB MORRISON, AR SILVER, SM MULVANEY, FD AF ROSS, RJ BALL, WA DINGES, DF KRIBBS, NB MORRISON, AR SILVER, SM MULVANEY, FD TI RAPID EYE-MOVEMENT SLEEP DISTURBANCE IN POSTTRAUMATIC-STRESS-DISORDER SO BIOLOGICAL PSYCHIATRY LA English DT Article DE POSTTRAUMATIC STRESS DISORDER; RAPID EYE MOVEMENT SLEEP; NIGHTMARES; PHASIC ACTIVITY; MAJOR DEPRESSION; ALCOHOL ABUSE ID CORTISOL EXCRETION; DEPRESSED-PATIENTS; STARTLE RESPONSE; REM; HYPOTHESIS; SPIKES; BRAIN; STATE AB The subjective sleep disturbance in posttraumatic stress disorder (PTSD), including the repetitive, stereotypical anxiety dream, suggests dysfunctional rapid eye movement (REM) sleep mechanisms. The polysomnograms of a group of physically healthy combat veterans with current PTSD were compared with those of an age-appropriate normal control group. Tonic and phasic REM sleep measures in the PTSD subjects were elevated on the second night of recorded sleep. Increased phasic REM sleep activity persisted in the PTSD group on the subsequent night. During the study, an anxiety dream occurred in a PTSD subject in REM sleep. The results are consistent with the view that a dysregulation of the REM sleep control system, particularly phasic event generation, may be involved in the pathogenesis of PTSD. The finding of a specific disturbance of sleep unique to PTSD may have significant implications for the design of effective treatments for PTSD. C1 PHILADELPHIA VET AFFAIRS MED CTR,RES SERV,PHILADELPHIA,PA. UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH VET MED,DEPT ANIM BIOL,PHILADELPHIA,PA 19104. COATESVILLE VET AFFAIRS MED CTR,COATESVILLE,PA. FU NIMH NIH HHS [F32-MH-09584-01, MH-42903] NR 36 TC 123 Z9 126 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD FEB 1 PY 1994 VL 35 IS 3 BP 195 EP 202 DI 10.1016/0006-3223(94)91152-5 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MY642 UT WOS:A1994MY64200007 PM 8173020 ER PT J AU CANNON, SC AF CANNON, SC TI SLOW SODIUM-CHANNEL INACTIVATION NEED NOT BE DISRUPTED IN THE PATHOGENESIS OF MYOTONIA AND PERIODIC PARALYSIS - REPLY SO BIOPHYSICAL JOURNAL LA English DT Letter RP CANNON, SC (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 7 TC 5 Z9 5 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP 543 EP 544 PG 2 WC Biophysics SC Biophysics GA MU275 UT WOS:A1994MU27500032 ER PT J AU BERK, DA YUAN, F LEUNIG, M JAIN, RK AF BERK, DA YUAN, F LEUNIG, M JAIN, RK TI INTERSTITIAL TRANSPORT OF BINDING AND NON-BINDING ANTIBODIES IN THICK TISSUE MEASURED WITH FRAP SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RI Berk, David/A-4863-2012 OI Berk, David/0000-0002-3855-6886 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A278 EP A278 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46201610 ER PT J AU BOGDANOV, K PEPE, S TALO, A SPURGEON, HA LEAF, A HALLAQ, H LAKATTA, EG AF BOGDANOV, K PEPE, S TALO, A SPURGEON, HA LEAF, A HALLAQ, H LAKATTA, EG TI DOCOSAHEXAENOIC ACID MODULATES NITRENDIPINE EFFECTS ON CALCIUM CHANNELS AND CONTRACTION IN ADULT-RAT CARDIAC MYOCYTES SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A423 EP A423 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46202460 ER PT J AU CANTIELLO, HF LIN, EC AF CANTIELLO, HF LIN, EC TI ELECTRODYNAMIC PROPERTIES OF ACTIN-FILAMENTS IN SOLUTION SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A195 EP A195 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46201135 ER PT J AU CHEN, CF CANNON, S AF CHEN, CF CANNON, S TI BETA-1 SUBUNIT MODULATION OF NA CHANNEL INACTIVATION DOES NOT OCCUR FROM THE CYTOPLASMIC SIDE SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,HHMI,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A243 EP A243 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46201418 ER PT J AU DALTON, LA RAINES, DE MILLER, KW AF DALTON, LA RAINES, DE MILLER, KW TI ETHANOL DISRUPTS SLOW MOTIONS OF THE PROTEIN - ASSOCIATED LIPID NEAR-THE-SURFACE OF ACETYLCHOLINE-RECEPTORS SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A56 EP A56 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46200318 ER PT J AU FESCHENKO, MS SWEADNER, KJ AF FESCHENKO, MS SWEADNER, KJ TI CONFORMATION AFFECTS PHOSPHORYLATION OF NA,K-ATPASE BY KINASES SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A116 EP A116 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46200669 ER PT J AU HALL, JE BRISSETTE, J GILULA, NB KUMAR, N DOTTO, P AF HALL, JE BRISSETTE, J GILULA, NB KUMAR, N DOTTO, P TI DIFFERENTIATING KERATINOCYTES EXPRESS DIFFERENT GAP-JUNCTION PROTEINS AND HAVE DIFFERENT JUNCTIONAL SELECTIVITY SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 UNIV CALIF IRVINE, DEPT PHYSIOL & BIOPHYS, IRVINE, CA 92717 USA. HARVARD UNIV, SCH MED, CTR CUTANEOUS BIOL, DEPT DERMATOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, E CHARLESTOWN, MA 02129 USA. Scripps Res Inst, DEPT CELL BIOL, LA JOLLA, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A261 EP A261 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46201512 ER PT J AU KISTER, AE MALINSKY, J SMOLYAR, A REINHERZ, EL AF KISTER, AE MALINSKY, J SMOLYAR, A REINHERZ, EL TI A THEORETICAL-MODEL OF ANTIGEN RECOGNITION BY A T-CELL RECEPTOR AND ITS POSSIBLE IMPLICATIONS FOR SIGNAL-TRANSDUCTION SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A66 EP A66 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46200377 ER PT J AU LONDON, B HILL, JA NADALGINARD, B LOGOTHETIS, DA AF LONDON, B HILL, JA NADALGINARD, B LOGOTHETIS, DA TI CLONING AND EXPRESSION OF THE GENE ENCODING THE MURINE DELAYED RECTIFIER POTASSIUM CHANNEL KV1.5 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A106 EP A106 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46200611 ER PT J AU MCLAUGHLIN, J HAWROT, E YELLEN, G AF MCLAUGHLIN, J HAWROT, E YELLEN, G TI NICOTINIC RECEPTOR LIGAND-BINDING DOMAIN PROBED BY CYSTEINE-SUBSTITUTION MUTAGENESIS SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BROWN UNIV,PROVIDENCE,RI 02912. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A349 EP A349 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46202029 ER PT J AU PRAT, AG CANTIELLO, HF AF PRAT, AG CANTIELLO, HF TI ACTIN PHOSPHORYLATION BY PROTEIN KINASE-A AND KINASE-C EFFECTS EPITHELIAL SODIUM-CHANNEL REGULATION SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A244 EP A244 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46201420 ER PT J AU RANKIN, SE MILLER, KW AF RANKIN, SE MILLER, KW TI THE EFFECT OF THE LIPID BILAYER ON THE AFFINITY STATE TRANSITIONS OF THE NICOTINIC ACETYLCHOLINE-RECEPTOR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A257 EP A257 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46201488 ER PT J AU SCARLATA, S LEE, J PILCH, P SHOELSON, S AF SCARLATA, S LEE, J PILCH, P SHOELSON, S TI INSULIN BINDING AND ACTIVATION OF THE INSULIN-RECEPTOR AS CHARACTERIZED BY FLUORESCENCE SPECTROSCOPY SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 SUNY STONY BROOK,DEPT PHYSIOL & BIOPHYS,STONY BROOK,NY 11794. BOSTON UNIV,BOSTON,MA 02118. HARVARD UNIV,SCH MED,JOSLIN DIAB CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A49 EP A49 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46200276 ER PT J AU WU, G MILLER, KW AF WU, G MILLER, KW TI A NOVEL MODE OF INACTIVATION OF NICOTINIC ACETYLCHOLINE-RECEPTOR BY A NONCOMPETITIVE INHIBITOR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A257 EP A257 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46201490 ER PT J AU YELLEN, G SODICKSON, D CHEN, TY JURMAN, M AF YELLEN, G SODICKSON, D CHEN, TY JURMAN, M TI STRUCTURAL-CHANGES IN THE OUTER MOUTH OF K+ CHANNELS ACCOMPANYING C-TYPE INACTIVATION SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 1994 VL 66 IS 2 BP A23 EP A23 PN 2 PG 1 WC Biophysics SC Biophysics GA MU462 UT WOS:A1994MU46200129 ER PT J AU MUNRO, JM FREEDMAN, AS ASTER, JC GRIBBEN, JG LEE, NC RHYNHART, KK BANCHEREAU, J NADLER, LM AF MUNRO, JM FREEDMAN, AS ASTER, JC GRIBBEN, JG LEE, NC RHYNHART, KK BANCHEREAU, J NADLER, LM TI IN-VIVO EXPRESSION OF THE B7 COSTIMULATORY MOLECULE BY SUBSETS OF ANTIGEN-PRESENTING CELLS AND THE MALIGNANT-CELLS OF HODGKINS-DISEASE SO BLOOD LA English DT Article ID T-CELLS; MONOCLONAL-ANTIBODIES; DENDRITIC CELLS; ACTIVATION; CD28; LYMPHOCYTES; AMPLIFICATION; INTERLEUKIN-2; MECHANISM; SELECTION C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. SCHERING PLOUGH CORP,DARDILLY,FRANCE. FU NCI NIH HHS [5R01-CA40216, CA55207] NR 28 TC 89 Z9 89 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 FEB 1 PY 1994 VL 83 IS 3 BP 793 EP 798 PG 6 WC Hematology SC Hematology GA MU302 UT WOS:A1994MU30200024 PM 7507734 ER PT J AU ROCHON, E WATERS, GS CAPLAN, D AF ROCHON, E WATERS, GS CAPLAN, D TI SENTENCE COMPREHENSION IN PATIENTS WITH ALZHEIMERS-DISEASE SO BRAIN AND LANGUAGE LA English DT Article ID MINI-MENTAL STATE; SENILE DEMENTIA; SYNTACTIC COMPREHENSION; SEMANTIC IMPAIRMENT; LANGUAGE PRODUCTION; APHASIA; SPEECH; MEMORY C1 MCGILL UNIV,SCH COMMUN SCI & DISORDERS,MONTREAL H3G 1A8,PQ,CANADA. MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPSYCHOL LAB,BOSTON,MA 02114. OI Rochon, Elizabeth/0000-0001-5521-0513 FU NIDCD NIH HHS [DC00942-01] NR 54 TC 83 Z9 84 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 FEB PY 1994 VL 46 IS 2 BP 329 EP 349 DI 10.1006/brln.1994.1018 PG 21 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA MT889 UT WOS:A1994MT88900008 PM 8137148 ER PT J AU BAMEZAI, A ROCK, KL AF BAMEZAI, A ROCK, KL TI A ROLE OF LY-6A.2 IN T-LYMPHOCYTE ACTIVATION AND DEVELOPMENT SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT GPI-Anchor Proteins: Structure and Function - 1994 Meeting CY FEB 20-26, 1994 CL ANGRA DOS REIS, BRAZIL DE LY-6A.2; T-LYMPHOCYTES; ACTIVATION; GPI (GLYCOSYLPHOSPHATIDYLINOSITOL) ID CELL ACTIVATION; GLYCOSYL-PHOSPHATIDYLINOSITOL; MULTIGENE FAMILY; RECEPTOR COMPLEX; MEMBRANE; PROTEINS; STIMULATION; TAP; EXPRESSION; ANTIGEN AB Ly-6A.2 is a glycosylphosphatidylinositol (GPI)-anchored protein expressed on the plasma membrane of T lymphocytes. The precise function of this molecule is not known. A role of Ly-6A.2 in T cell signaling is discussed. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP BAMEZAI, A (reprint author), DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD FEB PY 1994 VL 27 IS 2 BP 283 EP 288 PG 6 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA MX609 UT WOS:A1994MX60900026 PM 8081241 ER PT J AU MARGOLIS, ML HYZY, JB SCHENKEN, LL SCHEPART, BS AF MARGOLIS, ML HYZY, JB SCHENKEN, LL SCHEPART, BS TI SERUM TUMOR-MARKERS IN NONSMALL CELL LUNG-CANCER - A COMPARATIVE-ANALYSIS SO CANCER LA English DT Article DE TUMOR MARKERS; MONOCLONAL ANTIBODIES; NONSMALL CELL LUNG CANCER ID MULTIPLE BIOMARKER ASSAY; MONOCLONAL-ANTIBODIES; CLINICAL-SIGNIFICANCE; CARCINOMA; DIAGNOSIS; ANTIGENS AB Background. The role of serum tumor markers in non-small cell lung cancer (NSCLC) remains undefined. New proposed markers have seldom been rigorously compared with existing standards. The authors prospectively compared the performance of three new monoclonal antibodies (MoAb) (5E8, 5C7, and 1F10) with the established serum markers carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC). Methods. The cohort consisted of 45 consecutive outpatients with newly diagnosed NSCLC. Control subjects were 38 outpatients with non-neoplastic chronic pulmonary diseases. Blood from each patient and control subject was assayed for all five tumor markers. An enzyme linked immunosorbent assay (ELISA) was used to determine 5E8, 5C7, and 1F10 reactivity. Commercially available kits were used to measure SCC by radioimmunoassay and CEA by ELISA. Individual and combinations of tumor markers were compared in terms of sensitivity, specificity, and accuracy for NSCLC diagnosis. Results. 5E8 plus 5C7 plus 1F10 significantly surpassed SCC plus CEA in terms of sensitivity (P < 0.05) and proved the most accurate marker combination. Among single markers, 5E8 was most specific, 5C7 most sensitive, and 5C7 and 1F10 each most accurate, but differences from CEA alone were not significant. Subgroup analysis by histologic type and stage demonstrated similar findings, and marker combinations yielded little additional diagnostic benefit. Conclusions. 5E8, 5C7, and 1F10 performed marginally better than did CEA and SCC in patients with newly diagnosed NSCLC. Many limitations apply in defining a clinical niche for these tumor markers in NSCLC, although 5E8, 5C7, and 1F10 previously have demonstrated a modest prognostic value. An adjunctive role in a few specific clinical contexts remains possible. C1 MED COLL PENN,PHILADELPHIA,PA. MED COLL PENN,DEPT MED,PHILADELPHIA,PA 19129. ALLEGHENY GEN HOSP,CLIN ONCOL LAB,PITTSBURGH,PA. RP MARGOLIS, ML (reprint author), VET AFFAIRS MED CTR,PULM DIS SECT,PHILADELPHIA,PA 19104, USA. NR 20 TC 26 Z9 27 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 FEB 1 PY 1994 VL 73 IS 3 BP 605 EP 609 DI 10.1002/1097-0142(19940201)73:3<605::AID-CNCR2820730317>3.0.CO;2-T PG 5 WC Oncology SC Oncology GA MU681 UT WOS:A1994MU68100016 PM 8299082 ER PT J AU WITTE, RS ELSON, P KHANDAKAR, J TRUMP, DL AF WITTE, RS ELSON, P KHANDAKAR, J TRUMP, DL TI AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP PHASE-II TRIAL OF TRIMETREXATE IN THE TREATMENT OF ADVANCED UROTHELIAL CARCINOMA SO CANCER LA English DT Article DE ANTIFOL; TRIMETREXATE; UROTHELIAL NEOPLASMS; METHOTREXATE; BLADDER CANCER ID TRANSITIONAL CELL-CARCINOMA; METHOTREXATE; VINBLASTINE; CISPLATIN; CHEMOTHERAPY; DOXORUBICIN; EFFICACY; CANCER; TRACT AB Background. Trimetrexate is an antifol that differs from methotrexate in ways that may be clinically important. Because methotrexate has activity in advanced bladder cancer, this trial was initiated. Methods. Ambulatory patients with advanced urothelial carcinoma were treated with the nonclassic antifol trimetrexate at the intravenous dose of 8 mg/m(2) daily for 5 consecutive days every 3 weeks (4 mg/m(2) daily for 5 consecutive days for patients with creatinine levels greater than 1.6 mg/dl). Results. Of the 48 patients in the study, one had a complete response and seven had partial responses, for an overall response rate of 17% (exact 95% confidence interval, 7-30%). The response rate in patients who had received prior methotrexate was 18%, suggesting lack of complete cross-resistance. Toxicity was manageable and primarily mucosal, gastrointestinal, and myelosuppressive. Conclusions. Trimetrexate has as much activity as other single agents in advanced urothelial carcinoma. Combination therapy, possibly with cisplatin, platinum analogs, or other antifols, using trimetrexate should be studied. C1 UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI. DANA FARBER CANC INST,BOSTON,MA. NORTHWESTERN UNIV,MED CTR,CHICAGO,IL 60611. FU NCI NIH HHS [CA 17145, CA 23318, CA 21076] NR 17 TC 38 Z9 38 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 FEB 1 PY 1994 VL 73 IS 3 BP 688 EP 691 DI 10.1002/1097-0142(19940201)73:3<688::AID-CNCR2820730330>3.0.CO;2-V PG 4 WC Oncology SC Oncology GA MU681 UT WOS:A1994MU68100029 PM 8299090 ER PT J AU MACKLIS, RM BERESFORD, BA HUMM, JL AF MACKLIS, RM BERESFORD, BA HUMM, JL TI RADIOBIOLOGICAL STUDIES OF LOW-DOSE-RATE Y-90 LYMPHOMA THERAPY SO CANCER LA English DT Article; Proceedings Paper CT 9th Conference on Radioimmunodetection and Radioimmunotherapy of Cancer CY SEP 17-19, 1992 CL PRINCETON, NJ DE APOPTOSIS; RADIOBIOLOGY; RADIOLABELED ANTIBODY THERAPY; RADIATION DOSE-RATE EFFECTS; CAFFEINE ID CELL-DEATH; RADIOIMMUNOTHERAPY; APOPTOSIS; TUMOR AB Background. Radioimmunotherapy and other forms of biologically targeted radiopharmaceutic treatment appear to show unexpected efficacy in many patients with lymphoma, neuroblastoma, and several other types of nonepithelial malignancies. The radiobiologic mechanisms responsible for this high clinical radioresponsiveness are unclear, but must involve some sort of cytotoxic enhancement or sensitization to protracted courses of low-dose-rate radiation exposure. Materials and Methods. A series of in vitro experiments was performed with malignant lymphoma cell lines exposed under various conditions to high-dose-rate external beam radiotherapy or low-dose-rate 90Y radiation. Data were collected on cell cycle effects, DNA fragmentation, and modulation of cytotoxicity by caffeine and treatment sequence alterations. Results. The data showed that some malignant lymphoma lines are highly sensitive to low-dose-rate radiation and that a portion of the cytotoxicity appears to be mediated by the induction of radiation-associated apoptosis (programmed cell death). Cell cycle effects of low-dose-rate radiation (such as G2M block) appear to be relatively minor in this experimental system. Agents that modulate apoptosis (such as the calcium-releasing agent caffeine) significantly enhance cell kill and DNA fragmentation after 90Y treatment. Conclusions. These results suggest that radiation-associated apoptosis may be important in the radiobiology of targeted radiopharmaceutical therapy. C1 HARVARD UNIV,JOINT CTR RADIAT THERAPY,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA. FU NCI NIH HHS [R29CA49017] NR 19 TC 36 Z9 37 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 FEB 1 PY 1994 VL 73 IS 3 SU S BP 966 EP 973 DI 10.1002/1097-0142(19940201)73:3+<966::AID-CNCR2820731332>3.0.CO;2-G PG 8 WC Oncology SC Oncology GA MV418 UT WOS:A1994MV41800031 PM 8306286 ER PT J AU KATSANIS, E BAUSERO, MA XU, H ORCHARD, PJ XU, ZY MCIVOR, RS BRIAN, AA BLAZAR, BR AF KATSANIS, E BAUSERO, MA XU, H ORCHARD, PJ XU, ZY MCIVOR, RS BRIAN, AA BLAZAR, BR TI TRANSFECTION OF THE MOUSE ICAM-1 GENE INTO MURINE NEUROBLASTOMA ENHANCES SUSCEPTIBILITY TO LYSIS, REDUCES IN-VIVO TUMORIGENICITY AND DECREASES ICAM-2-DEPENDENT KILLING SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE NEUROBLASTOMA; CYTOLYSIS; ICAM-1; ICAM-2; TUMORIGENICITY ID INTERCELLULAR-ADHESION MOLECULE-1; NATURAL-KILLER CELLS; NEURO-BLASTOMA; INTERFERON-GAMMA; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODIES; MEDIATED LYSIS; LYMPHOCYTES-T; CYTO-TOXICITY; TUMOR-CELLS AB We determined the expression of intercellular adhesion molecules (ICAM) on neuro-2a cells in order to evaluate whether they were involved in cytolysis of murine neuroblastoma. Fluorescence-activated cell sorting analysis revealed that the control neomycin-resistance-gene-transduced line (neuro-2a/LN) had poor expression of ICAM-1 (mean channel fluorescence, MCF = 3.7). An ICAM-1-positive transfectant of neuro-2a (neuro-2a/ICAM-1(+)) (MCF = 64.3) was generated to evaluate directly the role of this adhesion molecule in cytolysis. Neuro-2a/ICAM-1(+) was more sensitive to LAK killing (69.7% at an effector-to-target ratio of 100: 1) compared to neuro-2a/LN (48.6%) (P <0.001). Blocking of neuro2a/LN and neuro-2a/ICAM-1(+) lysis with anti-ICAM-1 monoclonal antibodies (mAbs) did not account for all the LFA-1-dependent killing. These data indicate that even in neuro-2a/ICAM-1(+) cells, other LFA-1 ligands participated in the effector-target interaction. Therefore, we examined these cell lines for ICAM-2 expression. Both neuro-2a/LN and neuro-2a/ICAM-1(+) lines expressed ICAM-2 (MCF = 16.4 and 16.5). ICAM-2 accounted for the majority of the LFA-l-dependent killing in the ICAM-1-negative target, neuro-2a/LN, while ICAM-1 played a primary role in the cytolysis of the ICAM-1(+) transfectant. Inhibition of lysis in the presence of anti-ICAM-1 and ICAM-2 mAbs was comparable to that seen with the addition of anti-LFA-1 mAb, indicating that other LFA-1 ligands were not involved in this system. ICAM-1 expression was associated with decreased in vivo tumorigenicity; mice inoculated with neuro-2a/ICAM-1(+) cells had a significantly longer survival compared to those receiving neuro-2a/LN cells (median survival time 35.5 versus 24.5 days) (P <0.001). It is important to note that ICAM-1 transfection of murine neuroblastoma did not alter its metastatic potential. We conclude that transfection of mouse neuroblastoma with ICAM-1 increases its sensitivity to in vitro lysis and reduces its in vivo tumorigenicity. In ICAM-1-negative murine neuroblastoma cells, ICAM-2 plays a primary role in cell-mediated lysis. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,CTR BLOOD RES,BOSTON,MA 02115. UNIV MINNESOTA,INST HUMAN GENET,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. UNIV CALIF SAN DIEGO,DEPT CHEM,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. RP KATSANIS, E (reprint author), UNIV MINNESOTA,DEPT PEDIAT,DIV PEDIAT HEMATOL ONCOL & BONE MARROW TRANSPLANT,MINNEAPOLIS,MN 55455, USA. FU NCI NIH HHS [P01-CA-21737]; NIAID NIH HHS [N01-AI-85002] NR 46 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD FEB PY 1994 VL 38 IS 2 BP 135 EP 141 DI 10.1007/BF01526209 PG 7 WC Oncology; Immunology SC Oncology; Immunology GA MU829 UT WOS:A1994MU82900009 PM 7905790 ER PT J AU SWISSHELM, K RYAN, K LEE, XH TSOU, HC PEACOCKE, M SAGER, R AF SWISSHELM, K RYAN, K LEE, XH TSOU, HC PEACOCKE, M SAGER, R TI DOWN-REGULATION OF RETINOIC ACID RECEPTOR-BETA IN MAMMARY-CARCINOMA CELL-LINES AND ITS UP-REGULATION IN SENESCING NORMAL MAMMARY EPITHELIAL-CELLS SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID BREAST-CANCER-CELLS; RESPONSE ELEMENT; NUCLEAR RECEPTOR; THYROID-HORMONE; GROWTH-INHIBITION; BINDING-PROTEINS; LUNG-CANCER; X-RECEPTOR; PS2 GENE; EXPRESSION AB Retinoids are important cellular, dietary factors that regulate differentiation and cellular growth. They serve as ligands for specific nuclear receptors, the retinoic acid receptors (RARs). Ligand-activated receptors regulate gene transcription through target retinoic acid-responsive elements (RAREs) found in promoter regions. We have investigated the expression of retinoic acid receptor genes (alpha, beta, gamma) and retinoid X receptor beta in normal, senescing, and tumorigenic human mammary epithelial cells. We find that most tumor cells show a loss of RAR-beta expression, but that RAR-alpha and -gamma as well as retinoid X receptor beta are variably expressed in both normal and tumor cells. RAR-beta gene expression is induced both by retinoic acid and by fenretinide in normal cells, but tumor cells fail to respond to either. In contrast, RAR-beta expression increases with serial passage in senescing cells. Paradoxically, both normal and tumor cells can trans-activate an exogenous beta-RARE, as demonstrated by reporter gene assays. Oligonucleotide mobility shift assays with the beta-RARE show a single discrete complex in normal cells, whereas tumor cells exhibit a heterogeneous set of larger complexes, which indicates that tumor cells utilize a different array of factors within the beta-RARE. Reporter gene assays with extended promoter regions indicate the presence of negative regulatory elements and/or factor binding sites that reside between -1500 and the RARE located at -59, and that the promoter is down-regulated in MCF-7 tumor cells. Our findings reveal a dichotomy: RAR-beta transcription is down-regulated in tumor cells compared. with normal human mammary epithelial cells, and up-regulated in senescence. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOLEC GENET,BOSTON,MA 02115. TUFTS UNIV NEW ENGLAND MED CTR,DEPT DERMATOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA-39814, T32 CA-09361]; NIA NIH HHS [AG-10819] NR 77 TC 207 Z9 213 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD FEB PY 1994 VL 5 IS 2 BP 133 EP 141 PG 9 WC Cell Biology SC Cell Biology GA MW525 UT WOS:A1994MW52500004 PM 8180126 ER PT J AU NAGATSU, M ZILE, MR TSUTSUI, H SCHMID, PG DEFREYTE, G COOPER, G CARABELLO, BA AF NAGATSU, M ZILE, MR TSUTSUI, H SCHMID, PG DEFREYTE, G COOPER, G CARABELLO, BA TI NATIVE BETA-ADRENERGIC SUPPORT FOR LEFT-VENTRICULAR DYSFUNCTION IN EXPERIMENTAL MITRAL REGURGITATION NORMALIZES INDEXES OF PUMP AND CONTRACTILE FUNCTION SO CIRCULATION LA English DT Article DE CONTRACTILITY; MITRAL VALVE; REGURGITATION RECEPTORS; ADRENERGIC; BETA ID CONGESTIVE HEART-FAILURE; SYSTOLIC PRESSURE-VOLUME; IDIOPATHIC DILATED CARDIOMYOPATHY; CANINE LEFT-VENTRICLE; WALL STRESS; PLASMA NOREPINEPHRINE; OVERLOAD HYPERTROPHY; MYOCARDIAL STIFFNESS; REGIONAL WORK; END-SYSTOLE AB Background It is generally accepted that the adrenergic nervous system provides inotropic support for the failing heart. However, the magnitude of this support has never been studied extensively. The present study was performed to test the hypothesis that the adrenergic nervous system is capable of maintaining indexes of pump and contractile function in the normal range despite significant innate myocardial depression. Methods and Results We used our model of experimental canine mitral regurgitation, which produces left ventricular dysfunction after 3 months of volume overload. We studied indexes of contractile function on and off beta-blockade at baseline and again on and off beta-blockade 3 months after chronic mitral regurgitation had induced significant contractile dysfunction. At baseline, acute beta-blockade caused insignificant reductions in the mass-corrected slope of the end-ejection stress-volume relation (EESVR), the end-systolic stiffness constant, and the ejection fraction-end-systolic stress and the mean velocity of circumferential fiber shortening (VCF)-end-systolic stress relations. After 3 months of chronic mitral regurgitation, all indexes of contractile function were normal in the unblocked state except for the VCF-stress relation, which was mildly reduced. However, after acute beta-blockade after 3 months of chronic mitral regurgitation, the EESVR fell to 303+/-27 versus 443+/-24 during acute beta-blockade before mitral regurgitation was created (P<.05), and the end-systolic stiffness constant was reduced to 2.54+/-0.15 versus 3.27+/-0.11 (P<.05). Only after beta-blockade was the ejection fraction-stress relation significantly reduced for dogs with chronic mitral regurgitation. The VCF-stress relation became markedly more abnormal. The viscosity-velocity relation of myocytes isolated from the ventricles of the dogs with mitral regurgitation confirmed that substantial innate contractile depression was present. Conclusions After 3 months of chronic mitral regurgitation, the adrenergic nervous system was able to maintain most indexes of contractile function in the normal range despite significant depression in innate contractile function. Thus, in the absence of beta-blockade, significant innate contractile depression may be obscured by adrenergic support. C1 MED UNIV S CAROLINA,GAZES CARDIAC RES INST,DEPT MED,DIV CARDIOL,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. UNIV IOWA,DEPT MED,IOWA CITY,IA 52242. RI Tsutsui, Hiroyuki/A-4070-2012 FU NHLBI NIH HHS [HL-38185] NR 46 TC 40 Z9 40 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB PY 1994 VL 89 IS 2 BP 818 EP 826 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA MW362 UT WOS:A1994MW36200036 PM 8313571 ER PT J AU SALADINO, R GARCIA, C THOMPSON, C HAMMER, B PARSONNET, J NOVITSKY, T SIBER, G FLEISHER, G AF SALADINO, R GARCIA, C THOMPSON, C HAMMER, B PARSONNET, J NOVITSKY, T SIBER, G FLEISHER, G TI EFFICACY OF A RECOMBINANT ENDOTOXIN NEUTRALIZING PROTEIN IN RABBITS WITH ESCHERICHIA-COLI SEPSIS SO CIRCULATORY SHOCK LA English DT Article DE SEPSIS; SEPTIC SHOCK; INFECTION; ENDOTOXIN; TUMOR NECROSIS FACTOR; BACTEREMIA; ESCHERICHIA COLI; ANIMAL MODEL ID TUMOR NECROSIS FACTOR; ANTI-LPS FACTOR; LIMULUS ANTILIPOPOLYSACCHARIDE FACTOR; PERMEABILITY-INCREASING PROTEIN; NEGATIVE BACTERIAL SEPSIS; HORSESHOE-CRAB; SEPTIC SHOCK; TACHYPLEUS-TRIDENTATUS; MONOCLONAL-ANTIBODY; DOUBLE-BLIND AB Gram-negative bacterial sepsis is associated with endotoxemia and a high mortality rate. In previous studies, we demonstrated the therapeutic benefit of an anti-lipopolysaccharide factor isolated from amebocytes of Limulus polyphemus, and of a recombinant version of this protein, termed endotoxin neutralizing protein (ENP), in rabbits challenged with purified lipopolysaccharides. To assess the benefit of ENP in treating a live bacterial infection, we established a rabbit model of Escherichia coli (E. coli) peritonitis and bacteremia with high mortality despite gentamicin treatment. Twenty-four pairs of New Zealand white rabbits were challenged intraperitoneally (IP) with E. coli O18ac K1 in 5% porcine mucin (mean bacteria per dose = 2.5 x 10(8)). The animals were treated with intravenous (IV) gentamicin (2.5 mg/kg), and with either ENP (5 mg/kg) or saline IV at 1 hr after E. coli challenge. All rabbits were bacteremic 1 hr after challenge (geometric mean 4.1 +/- 1.2 x 10(4) cfu/ml). Peak geometric mean serum endotoxin (2.62 v 10.54 EU/mL, P =.013) and tumor necrosis factor (TNF) (2540 v 6438 TNF units/mL, P =.046) concentrations were lower in ENP-treated animals as compared to control animals. Seven of 24 animals treated with ENP survived 24 hr compared with 4 of 24 controls (Kaplan-Meier analysis, P =.19). However, in the subgroup of 13 paired animals in whom bacteremia was eliminated by gentamicin treatment, 5 of 13 ENP-treated animals survived 24 hr, compared with 1 of 13 controls (Kaplan-Meier analysis, P =.032). We conclude that ENP treatment of rabbits with E. coli peritonitis and bacteremia lowers serum endotoxin and TNF concentrations, and improves survival, but only when bacteremia is eliminated by antibiotic therapy. (C) 1994 Wiley-Liss, Inc. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, INFECT DIS LAB, BOSTON, MA USA. DARTMOUTH HITCHOCK MED CTR, DEPT MED, DIV INFECT DIS, LEBANON, NH USA. ASSOCIATES CAPE COD INC, WOODS HOLE, MA USA. RP SALADINO, R (reprint author), HARVARD UNIV, CHILDRENS HOSP,SCH MED,DEPT MED,DIV EMERGENCY MED, 300 LONGWOOD AVE, BOSTON, MA 02115 USA. RI Hammer, Brian/I-7282-2013 FU NIAID NIH HHS [AI18125] NR 29 TC 22 Z9 24 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0092-6213 J9 CIRC SHOCK JI Circ. Shock PD FEB PY 1994 VL 42 IS 2 BP 104 EP 110 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA MZ052 UT WOS:A1994MZ05200006 PM 8013061 ER PT J AU WAHLSTROM, J OZELIUS, L KRAMER, P KYLLERMAN, M SCHUBACK, D FORSGREN, L HOLMGREN, G DRUGGE, U SANNER, G FAHN, S BREAKEFIELD, XO AF WAHLSTROM, J OZELIUS, L KRAMER, P KYLLERMAN, M SCHUBACK, D FORSGREN, L HOLMGREN, G DRUGGE, U SANNER, G FAHN, S BREAKEFIELD, XO TI THE GENE FOR FAMILIAL DYSTONIA WITH MYOCLONIC JERKS RESPONSIVE TO ALCOHOL IS NOT LOCATED ON THE DISTAL END OF 9Q SO CLINICAL GENETICS LA English DT Article DE CHROMOSOME-9; LINKAGE ANALYSIS; TORSION DYSTONIA ID AUTOSOMAL DOMINANT INHERITANCE; IDIOPATHIC TORSION DYSTONIA; SEGREGATION ANALYSIS; HUMAN CHROMOSOME-9; ASHKENAZI JEWS; 9Q32-34; LOCUS; REGION; POLYMORPHISM; PEDIGREES AB A gene (DYT1) for susceptibility to early-onset torsion dystonia in Ashkenazi Jewish and Gentile kindreds is situated on chromosome 9q32 q34 in a 6-7 cM span between markers AKI and ASS. To determine whether transmission of familial dystonia with myoclonic jerks responsive to alcohol was consistent with a gene in this region, we studied the 37 members of a Swedish family, of whom 20 were so affected. A lod score of < - 2.00 from a two-point linkage analysis with six DNA markers covering a 30 cM span from D9S26 to D9S10 that included the region of the DYT gene indicated that this gene is not located in this region, and that two or more autosomal loci are responsible for hereditary dystonia in humans. C1 EAST HOSP,DEPT PEDIAT 2,GOTHENBURG,SWEDEN. MASSACHUSETTS GEN HOSP,NEUROSCI CTR NEUROL,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. UMEA UNIV,DEPT NEUROL,S-90187 UMEA,SWEDEN. UMEA UNIV,DEPT CLIN GENET,S-90187 UMEA,SWEDEN. UMEA UNIV,DEPT SOCIOL,S-90187 UMEA,SWEDEN. KARLSTAD HOSP,DEPT CHILD REHABIL,KARLSTAD,SWEDEN. COLUMBIA UNIV COLL PHYS & SURG,DYSTONIA CLIN RES CTR,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032. RP WAHLSTROM, J (reprint author), EAST HOSP,DEPT CLIN GENET,S-41685 GOTHENBURG,SWEDEN. FU NINDS NIH HHS [NS28384] NR 35 TC 13 Z9 13 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD FEB PY 1994 VL 45 IS 2 BP 88 EP 92 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA NC691 UT WOS:A1994NC69100007 PM 8004804 ER PT J AU DRAYTON, J DICKINSON, G RINALDI, MG AF DRAYTON, J DICKINSON, G RINALDI, MG TI COADMINISTRATION OF RIFAMPIN AND ITRACONAZOLE LEADS TO UNDETECTABLE LEVELS OF SERUM ITRACONAZOLE SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 DEPT VET AFFAIRS MED CTR,DIV INFECT DIS,MIAMI,FL 33125. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. NR 1 TC 43 Z9 44 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 FEB PY 1994 VL 18 IS 2 BP 266 EP 266 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA MU350 UT WOS:A1994MU35000032 PM 8161649 ER PT J AU ESTOCK, DM HARRIS, WH AF ESTOCK, DM HARRIS, WH TI LONG-TERM RESULTS OF CEMENTED FEMORAL REVISION SURGERY USING 2ND-GENERATION TECHNIQUES - AN AVERAGE 11.7-YEAR FOLLOW-UP EVALUATION SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TOTAL HIP-REPLACEMENT; BONE-CEMENT; ARTHROPLASTY; FIXATION AB From a group of 43 hips in 41 patients, previously reported at an average of six years of follow-up evaluation, in whom second-generation cementing techniques were used during femoral revision hip surgery, 38 hips in 36 patients were rereviewed at an average follow-up period of 11.7 years (range, 118-172 months). The average age of the patients at the time of revision surgery was 52.8 years. Only four femoral components (10.5%) required rerevision for aseptic loosening. Of those not rerevised, the average Harris hip score at the time of follow-up evaluation was 81. Four additional hips (10.5%) had radiographic evidence of definite femoral component loosening. The survival of 90% of the implants of cemented femoral revision surgery and the 79% incidence of well-fixed femoral components for more than 11.7 years is attributed to the improved cementing techniques and modern stem design. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAD BIOMECH LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 49 TC 56 Z9 57 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 FEB PY 1994 IS 299 BP 190 EP 202 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA MV690 UT WOS:A1994MV69000027 PM 8119017 ER PT J AU DELMONICO, FL TOLKOFFRUBIN, N AUCHINCLOSS, H WILLIAMS, WW FANG, LT BAZARI, H FARRELL, ML COSIMI, AB AF DELMONICO, FL TOLKOFFRUBIN, N AUCHINCLOSS, H WILLIAMS, WW FANG, LT BAZARI, H FARRELL, ML COSIMI, AB TI MANAGEMENT OF THE RENAL-ALLOGRAFT RECIPIENT - IMMUNOSUPPRESSIVE PROTOCOLS FOR LONG-TERM SUCCESS SO CLINICAL TRANSPLANTATION LA English DT Article DE CYCLOSPORINE AND PREDNISONE WITHDRAWAL; TRIPLE DRUG IMMUNOSUPPRESSION; RENAL TRANSPLANT RECIPIENTS AB To determine the benefits of long-term cyclosporine (CsA) immunosuppression, renal allograft recipients were randomly assigned to a protocol of either: CsA + azathioprine (Aza) + prednisone (TD), or to a protocol in which CsA was discontinued from the regimen of Aza + prednisone (CsA D/C). With a mean follow-up of nearly 7 years since transplantation, 30/47 (64%) CsA D/C and 27/45 (60%) TD had functioning allografts. Although long-term survivals were similar, hazards of the CsA D/C protocol wen evident (40% rate of acute rejection following CsA DIC). Conversely, continued CsA in the TD protocol provided the opportunity for prednisone reduction, or even complete prednisone withdrawal in selected patients. A TD protocol which can provide equivalent long-term success, and eventually lower or omit prednisone, is preferable to a protocol of CsA D/C. RP DELMONICO, FL (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,GEN SURG SERV,TRANSPLANTAT UNIT,BOSTON,MA 02114, USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0063 J9 CLIN TRANSPLANT JI Clin. Transplant. PD FEB PY 1994 VL 8 IS 1 BP 34 EP 39 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA MW799 UT WOS:A1994MW79900008 PM 8136565 ER PT J AU GILLIS, BP CAGGIULA, AW JONES, FL MAURER, E MEEHAN, RM YAMAMOTO, ME STRIKER, GE KUSEK, JW AGODOA, LY ANDERSON, A KLAHR, S LEVEY, AS VARDAMAN, M BURKART, TJM FURBERG, CD FELTS, J MOORE, M ROCCO, M WARREN, S BEARDEN, B STARKEY, C DOLECEK, TA HARVEY, J POOLE, D DAHLQUIST, S DOROSHENKO, L BRADHAM, K WEST, D AGOSTINO, J COLE, LR BAKER, B HAIRSTON, K LAZARUS, M STEINMAN, TTI SEIFTER, JJ DESMOND, MA FIORENZO, MA CHIAVACCI, AT METALIDES, T KORZECRAMIREZ, D GOULD, SL PICKETT, V PORUSH, JG FAUBERT, PF SPITALEWITZ, S FAUBERT, JS ZIMMER, GS SAUM, DL BLOCK, M WOEL, J ROSE, MF DENNIS, VW SCHWAB, TSJ MINDA, SA CONDON, SM JENKS, BF ECKARD, L GEDON, G MITCH, WE MARONI, BJ ENGLAND, BK SOUCIE, M PEDERSEN, MF AKPELE, L CALLAHN, P HALL, B KOPPLE, JD ADLER, SG HIRSCHBERG, R DICHIRO, J SNIDER, K DEVINE, W MCKAY, S MCDONALD, JM CARTER, J NELSON, WJ COGGINS, CH DWYER, JT MCLAUGHLIN, ML GRONICH, J KING, AJ STOLLAR, C RAIZMAN, D CASTALDO, L DESIMONE, D EFSTATHION, A YONKER, K FINE, JA HUGGINS, N MARTIN, A BALDI, S MOLESKE, C FURLONG, D HEBERT, LA NAHMAN, NS DRIVER, V COSIO, MJ HARTMAN, JA LEVY, CS LONDERGAN, D GILLIGAN, M BECKMAN, TJ MILLER, J SMITH, E TISHER, CC PETERSON, JC WINGO, CS FINLAY, A PARRIS, ES IVEY, G GREGORY, P HOFFINGER, R GARCIA, D PRESTON, C HUNSICKER, LG BERTOLATUS, JA LIM, V SNETSELAAR, L WELCH, B BROOKS, LL HOLLINGER, DL LICHTY, I MUELLER, DK EASTIN, S TANNA, A STEELE, J RIECK, K BOURGOIGNIE, J ROTH, D GREEN, DF DEVALDERRAMA, CO MERRILL, D DEVELASCO, A GARCON, M ROJAS, C ZARAGOZA, M BARTON, A MASSRY, SG AKMAL, M FADDA, G SMORGORZERSKI, M KIEFER, S RAUCH, S EYERMAN, M KIGAWA, L LIFSCHITZ, MD NOLAN, CR GOUGE, S BAKRIS, G YOUNG, E ARMES, C WARNER, C TANSEY, A FIORES, MO DELEA, CS TESCHAN, PE HAKIM, RM BREYER, JA SCHULMAN, G ROGERS, NL POWERS, SN MCLEROY, S FISCHER, S DEERE, M CUTLER, EM BECK, GJ WILLIAMS, GW GASSMAN, JJ GREENE, T SCHLUCHTER, MD BERG, RL BROWN, M CHU, L DRABIK, MJ FATICA, KJ LAMBDIN, KE LEATHERMAN, JR MCPHERSON, JA MIDCALF, V MOORE, B SWINDERMAN, DM WEBB, L YANCHAR, KA MILAS, NC AMOROSO, WP AVERBACH, FA COYNE, T GILLIS, B MAURER, EA MEEHAN, RJ NAUJELIS, JA OLSON, MB SCHERCH, LK STANO, E CHUMLEA, WC WING, RR STEGINK, LD BRUMMEL, MC VANLENTE, F WALETZKY, JA ERDEI, LM SOUTH, CA SPAGNOLA, C OLAUGHLIN, C PROUDFIT, WL UNDERWOOD, DA HALL, PM ROLIN, HA PEXA, DS JONES, E BASCH, M DAMICO, G DIRKS, JH GRANTHAM, J HARPER, AE PETERS, K STEIN, JH PELLEGRINO, ED VANYPERSELE, C MYERS, BD GRIZZLE, JE HAWKINS, CM HOLLIDAY, MA RUDMAN, D YOUNG, DS YOUNG, V LUKE, R KAPLAN, RM BYINGTON, RP AF GILLIS, BP CAGGIULA, AW JONES, FL MAURER, E MEEHAN, RM YAMAMOTO, ME STRIKER, GE KUSEK, JW AGODOA, LY ANDERSON, A KLAHR, S LEVEY, AS VARDAMAN, M BURKART, TJM FURBERG, CD FELTS, J MOORE, M ROCCO, M WARREN, S BEARDEN, B STARKEY, C DOLECEK, TA HARVEY, J POOLE, D DAHLQUIST, S DOROSHENKO, L BRADHAM, K WEST, D AGOSTINO, J COLE, LR BAKER, B HAIRSTON, K LAZARUS, M STEINMAN, TTI SEIFTER, JJ DESMOND, MA FIORENZO, MA CHIAVACCI, AT METALIDES, T KORZECRAMIREZ, D GOULD, SL PICKETT, V PORUSH, JG FAUBERT, PF SPITALEWITZ, S FAUBERT, JS ZIMMER, GS SAUM, DL BLOCK, M WOEL, J ROSE, MF DENNIS, VW SCHWAB, TSJ MINDA, SA CONDON, SM JENKS, BF ECKARD, L GEDON, G MITCH, WE MARONI, BJ ENGLAND, BK SOUCIE, M PEDERSEN, MF AKPELE, L CALLAHN, P HALL, B KOPPLE, JD ADLER, SG HIRSCHBERG, R DICHIRO, J SNIDER, K DEVINE, W MCKAY, S MCDONALD, JM CARTER, J NELSON, WJ COGGINS, CH DWYER, JT MCLAUGHLIN, ML GRONICH, J KING, AJ STOLLAR, C RAIZMAN, D CASTALDO, L DESIMONE, D EFSTATHION, A YONKER, K FINE, JA HUGGINS, N MARTIN, A BALDI, S MOLESKE, C FURLONG, D HEBERT, LA NAHMAN, NS DRIVER, V COSIO, MJ HARTMAN, JA LEVY, CS LONDERGAN, D GILLIGAN, M BECKMAN, TJ MILLER, J SMITH, E TISHER, CC PETERSON, JC WINGO, CS FINLAY, A PARRIS, ES IVEY, G GREGORY, P HOFFINGER, R GARCIA, D PRESTON, C HUNSICKER, LG BERTOLATUS, JA LIM, V SNETSELAAR, L WELCH, B BROOKS, LL HOLLINGER, DL LICHTY, I MUELLER, DK EASTIN, S TANNA, A STEELE, J RIECK, K BOURGOIGNIE, J ROTH, D GREEN, DF DEVALDERRAMA, CO MERRILL, D DEVELASCO, A GARCON, M ROJAS, C ZARAGOZA, M BARTON, A MASSRY, SG AKMAL, M FADDA, G SMORGORZERSKI, M KIEFER, S RAUCH, S EYERMAN, M KIGAWA, L LIFSCHITZ, MD NOLAN, CR GOUGE, S BAKRIS, G YOUNG, E ARMES, C WARNER, C TANSEY, A FIORES, MO DELEA, CS TESCHAN, PE HAKIM, RM BREYER, JA SCHULMAN, G ROGERS, NL POWERS, SN MCLEROY, S FISCHER, S DEERE, M CUTLER, EM BECK, GJ WILLIAMS, GW GASSMAN, JJ GREENE, T SCHLUCHTER, MD BERG, RL BROWN, M CHU, L DRABIK, MJ FATICA, KJ LAMBDIN, KE LEATHERMAN, JR MCPHERSON, JA MIDCALF, V MOORE, B SWINDERMAN, DM WEBB, L YANCHAR, KA MILAS, NC AMOROSO, WP AVERBACH, FA COYNE, T GILLIS, B MAURER, EA MEEHAN, RJ NAUJELIS, JA OLSON, MB SCHERCH, LK STANO, E CHUMLEA, WC WING, RR STEGINK, LD BRUMMEL, MC VANLENTE, F WALETZKY, JA ERDEI, LM SOUTH, CA SPAGNOLA, C OLAUGHLIN, C PROUDFIT, WL UNDERWOOD, DA HALL, PM ROLIN, HA PEXA, DS JONES, E BASCH, M DAMICO, G DIRKS, JH GRANTHAM, J HARPER, AE PETERS, K STEIN, JH PELLEGRINO, ED VANYPERSELE, C MYERS, BD GRIZZLE, JE HAWKINS, CM HOLLIDAY, MA RUDMAN, D YOUNG, DS YOUNG, V LUKE, R KAPLAN, RM BYINGTON, RP TI FEATURES OF THE NUTRIENT DATABASE AND ANALYSIS SYSTEM FOR THE MODIFICATION OF DIET IN RENAL-DISEASE STUDY SO CONTROLLED CLINICAL TRIALS LA English DT Article DE NUTRIENT DATABASE; NUTRIENT CALCULATION; DIET; DIETARY ANALYSIS; RENAL DISEASE; CLINICAL TRIAL ID DATA-BASES AB This article describes the features of the nutrient database and analysis system developed for the Modification of Diet in Renal Disease (MDRD) Study and outlines the development process itself, an example of tailoring a database and analysis system for a complex, long-term clinical trial. The MDRD Study was a 15-center trial for men and women aged 18 to 70 years with chronic renal disease who were not on dialysis and who had not had a kidney transplant. The effects of three levels of protein and phosphorus intake and two levels of blood pressure management were assessed on the rate of decline in kidney function. This paper describes the development, structure, contents, and application of the nutrient database and analysis system that was used to enter, analyze, and report the MDRD Study dietary data. C1 UNIV PITTSBURGH,GRAD SCH PUBL HLTH,DEPT EPIDEMIOL,PITTSBURGH,PA 15213. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. BRIGHAM & WOMENS HOSP BETH ISRAEL HOSP,BOSTON,MA. BROOKDALE HOSP,MED CTR,BROOKLYN,NY. DUKE UNIV,SCH MED,DURHAM,NC. EMORY UNIV,ATLANTA,GA. GEORGE WASHINGTON UNIV,WASHINGTON,DC. UNIV CALIF LOS ANGELES,HARBOR MED CTR,TORRANCE,CA 90509. MASSACHUSETTS GEN HOSP,NEW ENGLAND MED CTR,BOSTON,MA. OHIO STATE UNIV,COLUMBUS,OH. UNIV FLORIDA,GAINESVILLE,FL. UNIV IOWA HOSP & CLIN,IOWA CITY,IA. UNIV MIAMI,JACKSON MEM HOSP,MED CTR,MIAMI,FL 33136. UNIV SO CALIF,LOS ANGELES,CA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. VANDERBILT UNIV,MED CTR,NASHVILLE,TN. CLEVELAND CLIN FDN,CLEVELAND,OH. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA. UNIV IOWA,IOWA CITY,IA. NR 30 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 1994 VL 15 IS 1 BP 44 EP 58 DI 10.1016/0197-2456(94)90027-2 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA NM877 UT WOS:A1994NM87700008 PM 8149770 ER PT J AU GERARD, C GERARD, NP AF GERARD, C GERARD, NP TI THE PRO-INFLAMMATORY 7-TRANSMEMBRANE SEGMENT RECEPTORS OF THE LEUKOCYTE SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID HUMAN INTERLEUKIN-8 RECEPTOR; FUNCTIONAL EXPRESSION; ACTIVATED NEUTROPHILS; SIGNAL TRANSDUCTION; C5A ANAPHYLATOXIN; MOLECULAR-CLONING AB The past few years have witnessed the convergence of research into inflammation and research on the C protein linked receptors; the receptors encoded by this gene family recognize the ligands C5a, interleukin 8 and related chemokines, such as platelet activating factor and formyl peptide. The theme that is emerging suggests that distinct signals at the cell surface feed into common pathways of cell activation. Different agonist functions may relate to G protein heterogeneity, kinetics of activation, receptor phosphorylation, and non-selective coupling of receptors with multiple varieties of G proteins. RP GERARD, C (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,CTR BLOOD RES,320 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 53 TC 116 Z9 118 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD FEB PY 1994 VL 6 IS 1 BP 140 EP 145 DI 10.1016/0952-7915(94)90045-0 PG 6 WC Immunology SC Immunology GA MW054 UT WOS:A1994MW05400021 PM 8172674 ER PT J AU HALPIN, C THORNTON, A HASSO, M AF HALPIN, C THORNTON, A HASSO, M TI LOW-FREQUENCY SENSORINEURAL LOSS - CLINICAL-EVALUATION AND IMPLICATIONS FOR HEARING-AID FITTING SO EAR AND HEARING LA English DT Article; Proceedings Paper CT 2nd Iowa International Hearing Aid Conference CY JUN 25-27, 1993 CL IOWA CITY, IA ID SPEECH RECOGNITION; ARTICULATION INDEX; TONE MASKING; SUDDEN; LISTENERS AB Spread of excitation in the cochlea places fundamental limits on the interpretation of audiometric pure-tone hearing loss as a simple map of dysfunction along the cochlear partition, and histologic evidence from human temporal bones will be presented to demonstrate the insensitivity of the audiogram to variations in pathology in the case of low-frequency hearing loss. This article will describe a clinical procedure using simultaneous pure-tone masking to improve upon the localization of cochlear disease, particularly for low-frequency hearing losses, and a model for using the Articulation Index (AI) to develop prognoses for hearing aid performance in these cases, which can then be tested. Fourteen patients with low-frequency hearing loss were divided into two groups based upon threshold shifts caused by a pure-tone masker: those that showed normal low-frequency threshold shifts and those that showed marked shifts at frequencies below the masker, indicating greater loss of function than shown by the unmasked audiogram. Hypothetical audiograms were then generated to model a complete loss of apical function for all patients. Measured speech recognition scores were then compared to AI predictions for the actual and hypothetical audiograms. Best agreement for the patients showing normal masking shifts was between the measured scores and the AI for the actual audiogram, whereas the best agreement for the patients showing marked shifts was with the AI for the hypothetical audiogram. The implications for hearing aid recommendation and fitting in these cases are discussed. RP HALPIN, C (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC-0007928] NR 51 TC 19 Z9 21 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD FEB PY 1994 VL 15 IS 1 BP 71 EP 81 DI 10.1097/00003446-199402000-00008 PG 11 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA NA416 UT WOS:A1994NA41600008 PM 8194681 ER PT J AU HOU, ZZ THORNTON, AR AF HOU, ZZ THORNTON, AR TI A MODEL TO EVALUATE AND MAXIMIZE HEARING-AID PERFORMANCE BY INTEGRATING THE ARTICULATION INDEX ACROSS LISTENING CONDITIONS SO EAR AND HEARING LA English DT Article; Proceedings Paper CT 2nd Iowa International Hearing Aid Conference CY JUN 25-27, 1993 CL IOWA CITY, IA ID SPEECH-INTELLIGIBILITY PREDICTIONS; RECOGNITION; IMPAIRMENT; NOISE AB A method for integrating the articulation index (AI) across listening conditions was developed and applied to a preliminary model for evaluating and optimizing Prescriptions of hearing aid characteristics. The model takes hearing threshold, masking of noise, self-masking of speech, high level cochlear distortion, and the peak-clipping effects of a hearing aid into account. The integrated AI (IAI) across a range of listening conditions is used as a criterion for evaluating a specific hearing aid response characteristic and calculating an optimal frequency-gain characteristic that maximizes the IAI. For a high-frequency hearing loss, the frequency-gain characteristics and IAI's derived from an optimal IAI (OIAI), POGO, and NAL prescriptions are compared for two of listening situations: a quiet setting and a setting with a signal-to-noise ratio of -3 dB. The results predict that, in quiet, the OIAI prescription is not significantly different from the well-established prescriptive procedures such as the POGO and the NAL. For the noise condition, however, the optimal IAI model is predicted to be better in terms of speech intelligibility. RP HOU, ZZ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT AUDIOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 28 TC 5 Z9 5 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD FEB PY 1994 VL 15 IS 1 BP 105 EP 112 PG 8 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA NA416 UT WOS:A1994NA41600013 PM 8194674 ER PT J AU ROONEY, JW HODGE, MR MCCAFFREY, PG RAO, A GLIMCHER, LH AF ROONEY, JW HODGE, MR MCCAFFREY, PG RAO, A GLIMCHER, LH TI A COMMON FACTOR REGULATES BOTH TH1-SPECIFIC AND TH2-SPECIFIC CYTOKINE GENE-EXPRESSION SO EMBO JOURNAL LA English DT Article DE INTERLEUKIN-2; INTERLEUKIN-4; T-CELL ACTIVATION; T-HELPER-1 AND T-HELPER-2 CELLS; TRANSCRIPTION ID T-CELL ACTIVATION; NF-KAPPA-B; INTERFERON-GAMMA; CYCLOSPORINE-A; NUCLEAR FACTOR; LYMPHOCYTES-T; PROMOTER; INVITRO; CLONES; IDENTIFICATION AB Murine T helper cell clones are classified into two distinct subsets, T helper 1 (Th1) and T helper 2 (Th2), on the basis of cytokine secretion patterns. Th1 clones produce interleukin-2 (IL-2), tumor necrosis factor-beta (TNF-beta) and interferon-gamma (IFN-gamma), while Th2 clones produce IL-4, IL-5, IL-6 and IL-10. These subsets differentially promote delayed-type hypersensitivity or antibody responses, respectively. The nuclear factor NF-AT is induced in Th1 clones stimulated through the T cell receptor-CD3 complex, and is required for IL-2 gene induction. The NF-AT complex consists of two components: NF-ATp, which pre-exists in the cytosol and whose appearance in the nucleus is induced by an increase of intracellular calcium, and a nuclear AP-1 component whose induction is dependent upon activation of protein kinase C (PKC). Here we report that the induction of the Th2-specific IL-4 gene in an activated Th2 clone involves an NF-AT complex that consists only of NF-ATp, and not the AP-1 component. On the basis of binding experiments we show that this 'AP-1-less' NF-AT complex is specific for the IL-4 promoter and does not reflect the inability of activated Th2 cells to induce the AP-1 component. We propose that NF-ATp is a common regulatory factor for both Th1 and Th2 cytokine genes, and that the involvement of PKC-dependent factors, such as AP-1, may help determine Th1-/Th2-specific patterns of gene expression. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 41 TC 152 Z9 153 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 1 PY 1994 VL 13 IS 3 BP 625 EP 633 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV864 UT WOS:A1994MV86400014 PM 8313907 ER PT J AU BOTTARO, A LANSFORD, R XU, LX ZHANG, J ROTHMAN, P ALT, FW AF BOTTARO, A LANSFORD, R XU, LX ZHANG, J ROTHMAN, P ALT, FW TI S-REGION TRANSCRIPTION PER-SE PROMOTES BASAL IGE CLASS SWITCH RECOMBINATION BUT ADDITIONAL FACTORS REGULATE THE EFFICIENCY OF THE PROCESS SO EMBO JOURNAL LA English DT Article DE CLASS SWITCHING; DNA RECOMBINATION; GENE TARGETING; IMMUNOGLOBULIN GENES; TRANSCRIPTION ID HEAVY-CHAIN SWITCH; MURINE B-CELLS; EPSILON-TRANSCRIPTS; TRANSGENIC MICE; INTERFERON-GAMMA; C-EPSILON; EXPRESSION; INTERLEUKIN-4; INDUCTION; GENE AB Stimulation of B lymphocytes with a combination of lipopolysaccharide (LPS) and interleukin-4 (ILA) induces germline transcription of and subsequent switching to the epsilon heavy chain constant region (Cepsilon) gene. Mature germline Cepsilon transcripts contain a non-coding exon (Iepsilon exon) spliced to the Cepsilon exons. To distinguish between the potential roles of germline transcription and those of germline transcripts in regulating the class switch process, we replaced the LPS- and IL-4-inducible Iepsilon promoter and exon in ES cells with an LPS-inducible Emu enhancer/V(H) promoter expression cassette. Wildtype, heterozygous or homozygous mutant ES cells were injected into RAG-2 deficient blastocysts to generate somatic chimeras in which all B cells derived from ES cells. In contrast to normal B cells, heterozygous and homozygous mutant B cells had substantial transcription through the epsilon switch recombination region (Sepsilon) following treatment with LPS alone and, under these conditions, both underwent low level switching (10- to 100-fold less than wildtype cells stimulated with LPS+IL4) to IgE production. Heterozygous mutant cells underwent switching to IgE at essentially wildtype levels when stimulated with LPS and IL4. However, homozyous mutant cells still showed extremely low levels of switching to IgE upon LPS and IL4 stimulation. Analyses of hybridomas from heterozygous mutants indicated that the mutation is cis-acting and normal switching to other isotypes indicated that it is specific for IgE. Thus transcription per se generates low levels of class switch recombination in the absence of I region sequences. However, we demonstrate for the first time that. for optimal efficiency, the process requires the presence of the intact I region and/or l region promoter in cis, implicating factors beyond transcription through the S region in the regulation of class switching. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT MICROBIOL,NEW YORK,NY 10032. RP BOTTARO, A (reprint author), CHILDRENS HOSP MED CTR,HOWARD HUGHES MED INST,BOSTON,MA 02115, USA. RI Lansford, Rusty/C-6956-2014 FU NIAID NIH HHS [AI-33450, AI-31541, AI-20047] NR 54 TC 176 Z9 177 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD FEB 1 PY 1994 VL 13 IS 3 BP 665 EP 674 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MV864 UT WOS:A1994MV86400019 PM 8313911 ER PT J AU KAY, TWH CHEDRESE, PJ JAMESON, JL AF KAY, TWH CHEDRESE, PJ JAMESON, JL TI GONADOTROPIN-RELEASING-HORMONE CAUSES TRANSCRIPTIONAL STIMULATION FOLLOWED BY DESENSITIZATION OF THE GLYCOPROTEIN HORMONE-ALPHA PROMOTER IN TRANSFECTED ALPHA-T3 GONADOTROPE CELLS SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; MESSENGER RIBONUCLEIC-ACIDS; LUTEINIZING-HORMONE; SUBUNIT GENE; PITUITARY-CELLS; DIFFERENTIAL REGULATION; PULSE AMPLITUDE; EXPRESSION; SECRETION; RESPONSES AB Pulsatile GnRH regulates the biosynthesis and secretion of gonadotropins. Continuous administration of GnRH is known to desensitize gonadotropin secretion, but its effects on gonadotropin gene expression are less well characterized. We used a cell line of gonadotrope lineage (alpha T3 cells) to examine GnRH regulation of glycoprotein hormone alpha-subunit gene transcription. The Lu-subunit promoter, linked to a luciferase reporter gene (alpha LUC), was stably transfected into alpha T3 cells. Treatment with GnRH stimulated alpha LUC activity 3-fold. Stimulation of alpha LUC by GnRH was transient, with maximal activity after 6 h of treatment, followed by a return to baseline after 24 h. Stimulation of alpha-promoter activity by GnRH was inhibited entirely by a 10-fold molar excess of antide, a GnRH antagonist. Antide partially blocked GnRH stimulation even when added 4 h after GnRH, suggesting that a brief exposure to GnRH is not sufficient for maximal transcriptional stimulation. alpha LUC activity was also stimulated by treatment with 8-bromo-cAMP (3.5-fold), phorbol 12-myristate 13-acetate (TPA; 2.6-fold), or Bay K 8644 (3.3-fold). To assess whether the transient nature of GnRH stimulation was due to transcriptional desensitization, cells were pretreated with GnRH, followed by a second treatment with GnRH, cAMP, TPA, or Bay K. After pretreatment with GnRH, no further stimulation was seen after the addition of GnRH or TPA, but alpha LUC activity was further stimulated after the addition of either cAMP or Bay K. These findings indicate that the pathway for transcriptional activation by GnRH is desensitized and suggest that GnRH also desensitizes TPA-mediated stimulation. Similarly, pretreatment with TPA, but not cAMP or Bay K, prevented subsequent stimulation by GnRH. We conclude that GnRH transiently stimulates alpha gene transcription and that desensitization occurs with continuous exposure to GnRH, probably because of down-regulation of the protein kinase-C pathway. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, THYROID UNIT, BOSTON, MA 02114 USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [NICHHD HD-28138, NICHHD HD-29164, N01-HD-0-2906] NR 36 TC 41 Z9 41 U1 0 U2 0 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 FEB PY 1994 VL 134 IS 2 BP 568 EP 573 DI 10.1210/en.134.2.568 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MV443 UT WOS:A1994MV44300009 PM 7507827 ER PT J AU JUPPNER, H SCHIPANI, E BRINGHURST, FR MCCLURE, I KEUTMANN, HT POTTS, JT KRONENBERG, HM ABOUSAMRA, AB SEGRE, GV GARDELLA, TJ AF JUPPNER, H SCHIPANI, E BRINGHURST, FR MCCLURE, I KEUTMANN, HT POTTS, JT KRONENBERG, HM ABOUSAMRA, AB SEGRE, GV GARDELLA, TJ TI THE EXTRACELLULAR AMINO-TERMINAL REGION OF THE PARATHYROID-HORMONE (PTH)/PTH-RELATED PEPTIDE RECEPTOR DETERMINES THE BINDING-AFFINITY FOR CARBOXYL-TERMINAL FRAGMENTS OF PTH-(1-34) SO ENDOCRINOLOGY LA English DT Article ID HUMAN GROWTH-HORMONE; EXPRESSION CLONING; MOLECULAR-CLONING; PROTEIN; DOMAIN; CELLS; CAMP; SITE AB The recombinant human PTH/PTH-related peptide (PTHrP) receptor, when transiently expressed in COS-7 cells, binds [Nle(8,18),Tyr(34)] bovine PTH-(7-34)amide [PTH-(7-34)], human PTH-(10-34)amide [PTH-(10-34)], and bovine PTH-(15-34)amide [PTH-(15-34)] with at least 50-fold higher affinity than does the rat receptor homolog. In contrast, PTH-(1-34) binding affinities are similar for both receptor homologs. To map those areas of the PTH/PTHrP receptors that determine the binding specificity for carboxyl-terminal fragments of PTH-(1-34), we constructed chimeric rat/human PTH/PTHrP receptors. These bound PTH-(1-34) with normal affinity and, therefore, must have an overall conformation that resembles that of native receptors. Chimeras with the amino-terminal extracellular domain of the human PTH/ PTHrP receptor have a considerably higher binding affinity for PTH-(7-34), PTH-(10-34), and PTH-(15-34) than do the reciprocal receptor constructs in which the amino-terminal region is from the rat PTH/PTHrP receptor. The opossum PTH/PTHrP receptor homolog also binds PTH-(7-34) with higher affinity than the rat receptor, and studies of rat/opossum chimeras confirm the importance of the amino-terminal extracellular domain in determining the PTH-(7-34) binding specificity. Mutant rat and human PTH/PTHrP receptors in which either residues 61-105 of the extracellular region or most of the intracellular tail were deleted have PTH-(7-34) binding characteristics indistinguishable from those of either wild-type receptor. These findings indicate that the amino-terminal extracellular region of the PTH/PTHrP receptor contains a domain(s) that largely determines the binding affinity of amino-terminally truncated PTH analogs. This region, therefore, is likely to constitute a site for ligand-receptor interaction. C1 MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP JUPPNER, H (reprint author), MASSACHUSETTS GEN HOSP, DEPT PEDIAT, ENDOCRINE UNIT, BOSTON, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK-11794] NR 35 TC 130 Z9 130 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 1994 VL 134 IS 2 BP 879 EP 884 DI 10.1210/en.134.2.879 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MV443 UT WOS:A1994MV44300050 PM 8299582 ER PT J AU JEFFREY, GP OATES, PS WANG, TC BABYATSKY, MW BRAND, SJ AF JEFFREY, GP OATES, PS WANG, TC BABYATSKY, MW BRAND, SJ TI SPASMOLYTIC POLYPEPTIDE - A TREFOIL PEPTIDE SECRETED BY RAT GASTRIC MUCOUS CELLS SO GASTROENTEROLOGY LA English DT Article ID MESSENGER-RNA; GENE-EXPRESSION; ACID-SECRETION; SEQUENCE; PSP; LOCALIZATION; STOMACH; INTESTINE; ESTROGEN; PROTEIN C1 MASSACHUSETTS GEN HOSP,NERPRC,CTR STUDY INFLAMMATORY BOWEL DIS,GASTROINTESTINAL UNIT,BOSTON,MA 02114. FU NIDDK NIH HHS [P30 DK 43351] NR 33 TC 96 Z9 99 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD FEB PY 1994 VL 106 IS 2 BP 336 EP 345 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MW567 UT WOS:A1994MW56700006 PM 8299900 ER PT J AU KARAPLIS, AC LUZ, A GLOWACKI, J BRONSON, RT TYBULEWICZ, VLJ KRONENBERG, HM MULLIGAN, RC AF KARAPLIS, AC LUZ, A GLOWACKI, J BRONSON, RT TYBULEWICZ, VLJ KRONENBERG, HM MULLIGAN, RC TI LETHAL SKELETAL DYSPLASIA FROM TARGETED DISRUPTION OF THE PARATHYROID HORMONE-RELATED PEPTIDE GENE SO GENES & DEVELOPMENT LA English DT Article DE PTHRP; GENE TARGETING; FETAL SKELETAL DEVELOPMENT; CHONDRODYSPLASIA; CHONDROCYTE DIFFERENTIATION ID HOMOLOGOUS RECOMBINATION; HUMORAL HYPERCALCEMIA; EMBRYONIC CHICK; MOUSE; EXPRESSION; MICE; GROWTH; BONE; LOCALIZATION; CARTILAGE AB The parathyroid hormone-related peptide (PTHrP) gene was disrupted in murine embryonic stem cells by homologous recombination, and the null allele was introduced into the mouse germ line. Mice homozygous for the PTHrP null mutation died postnatally, probably from asphyxia, and exhibited widespread abnormalities of endochondral bone development. Histological examination revealed a diminution of chondrocyte proliferation, associated with premature maturation of chondrocytes and accelerated bone formation. Analysis of earlier developmental stages revealed that disturbance in cartilage growth preceded abnormal endochondral bone formation. There were no morphological abnormalities apparent in other tissues. These results provide direct evidence implicating PTHrP in normal skeletal development and serve to emphasize its potential involvement in human osteochondrodysplasias. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT ORTHOPED SURG,ORTHOPED RES LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. GESELL STRAHLEN & UMWELTFORSCH MBH,INST PATHOL,W-8042 NEUHERBERG,GERMANY. FU NHLBI NIH HHS [HL37569]; NIDDK NIH HHS [DK11794] NR 49 TC 826 Z9 839 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD FEB 1 PY 1994 VL 8 IS 3 BP 277 EP 289 DI 10.1101/gad.8.3.277 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA MY086 UT WOS:A1994MY08600003 PM 8314082 ER PT J AU HUTTNER, KM SELSTED, ME OUELLETTE, AJ AF HUTTNER, KM SELSTED, ME OUELLETTE, AJ TI STRUCTURE AND DIVERSITY OF THE MURINE CRYPTDIN GENE FAMILY SO GENOMICS LA English DT Article ID DEFENSIN ANTIMICROBIAL PEPTIDES; SMALL-INTESTINE; CDNA CLONES; PANETH CELL; RABBIT NP-2; HUMAN HNP-1; 5' END; NEUTROPHILS; SEQUENCE; AID AB Cryptdins are antimicrobial peptides of the defensin family produced by mouse intestinal Paneth cells. Characterization of genomic and cDNA clones of cryptdins 1-3, 5, and 6 revealed that each of these genes has a two-exon structure. The prepro- and mature peptide coding regions are found on different exons separated by an intron of approximately 550 bp. The 5' ends of cryptdin mRNAs are distinguished by a 45-nucleotide untranslated sequence (UTS) encoded completely by the first exon. This feature contrasts with the extended 5' UTS of myeloid defensin mRNAs, which are coded by a third exon that appears to be unique to defensin genes expressed in hematopoietic cells. Sequencing of cryptdin cDNAs from both C3H/HeJ and 129/SVJ mouse small intestine demonstrated the presence of at least 16 different mRNAs, identifying cryptdins as the largest; known defensin family. Amplification of these two-exon crypt defensin genes, followed by mutation-induced divergence at a limited number of positions, may have played an important role in the development of a broad-spectrum enteric defense system in the mouse. (C) 1991 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. CHILDRENS HOSP,JOINT PROGRAM NEONATOL,BOSTON,MA 02115. UNIV CALIF IRVINE,COLL MED,DEPT PATHOL,IRVINE,CA 92717. UNIV CALIF IRVINE,COLL MED,DEPT MICROBIOL & MOLEC GENET,IRVINE,CA 92717. SHRINERS BURN INST,CELL BIOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. FU NIAID NIH HHS [AI22931, AI31696]; NIDDK NIH HHS [DK44632] NR 45 TC 71 Z9 87 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 0888-7543 J9 GENOMICS JI Genomics PD FEB PY 1994 VL 19 IS 3 BP 448 EP 453 DI 10.1006/geno.1994.1093 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA605 UT WOS:A1994NA60500006 PM 8188287 ER PT J AU GOFF, BA GOODMAN, A MUNTZ, HG FULLER, AF NIKRUI, N RICE, LW AF GOFF, BA GOODMAN, A MUNTZ, HG FULLER, AF NIKRUI, N RICE, LW TI SURGICAL STAGE-IV ENDOMETRIAL CARCINOMA - A STUDY OF 47 CASES SO GYNECOLOGIC ONCOLOGY LA English DT Article ID PHASE-II; CYCLOPHOSPHAMIDE; DOXORUBICIN; CANCER; CISPLATIN; ADENOCARCINOMA; CHEMOTHERAPY; COMBINATION; IRRADIATION; TRIAL RP GOFF, BA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VINCENT MEM GYNECOL ONCOL SERV,BOSTON,MA 02114, USA. NR 22 TC 75 Z9 76 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD FEB PY 1994 VL 52 IS 2 BP 237 EP 240 DI 10.1006/gyno.1994.1038 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA MX037 UT WOS:A1994MX03700017 PM 8314145 ER PT J AU HAYES, DF AF HAYES, DF TI ANGIOGENESIS AND BREAST-CANCER SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID FIBROBLAST GROWTH-FACTOR; TUMOR NECROSIS FACTOR; PRIMARY ENDOCRINE TREATMENT; ENDOTHELIAL-CELL GROWTH; PROGNOSTIC FACTORS; PRENEOPLASTIC LESIONS; INHIBITS ANGIOGENESIS; PENTOSAN POLYSULFATE; HEPARIN FRAGMENT; MAMMARY-GLAND C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP HAYES, DF (reprint author), DANA FARBER CANC INST,CTR BREAST EVALUAT,44 BINNEY ST,BOSTON,MA 02052, USA. NR 91 TC 33 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1994 VL 8 IS 1 BP 51 EP 71 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA MW742 UT WOS:A1994MW74200005 PM 7512088 ER PT J AU BROWN, M AF BROWN, M TI ESTROGEN-RECEPTOR MOLECULAR-BIOLOGY SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID DEPENDENT INVITRO TRANSCRIPTION; NEGATIVE BREAST-CANCER; DNA-BINDING DOMAIN; RESPONSIVE ELEMENT; GLUCOCORTICOID RECEPTORS; VITELLOGENIN PROMOTER; MONOCLONAL-ANTIBODIES; BASAL TRANSCRIPTION; ACTIVATION; GENE RP BROWN, M (reprint author), DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,44 BINNEY ST,BOSTON,MA 02115, USA. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 NR 70 TC 34 Z9 34 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1994 VL 8 IS 1 BP 101 EP 112 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA MW742 UT WOS:A1994MW74200007 PM 8150773 ER PT J AU SHAPIRO, CL AF SHAPIRO, CL TI BISPHOSPHONATES IN BREAST-CANCER PATIENTS WITH SKELETAL METASTASES SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID GROWTH FACTOR-BETA; BONE METASTASES; HYPERCALCEMIA; CARCINOMA; PAMIDRONATE; RESORPTION; INVITRO; QUALITY; LIFE; APD RP SHAPIRO, CL (reprint author), DANA FARBER CANC INST,CTR BREAST EVALUAT,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 53 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1994 VL 8 IS 1 BP 153 EP 163 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA MW742 UT WOS:A1994MW74200011 PM 8150777 ER PT J AU SHAPIRO, CL HENDERSON, IC AF SHAPIRO, CL HENDERSON, IC TI ADJUVANT THERAPY OF BREAST-CANCER SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID DISEASE-FREE SURVIVAL; PREMENOPAUSAL PATIENTS; CHEMOHORMONAL THERAPY; 2ND MALIGNANCIES; CLINICAL-TRIALS; PLUS TAMOXIFEN; DOSE-RESPONSE; CHEMOTHERAPY; CYCLOPHOSPHAMIDE; WOMEN C1 UNIV CALIF SAN FRANCISCO,DEPT MED,DIV HEMATOL ONCOL,SAN FRANCISCO,CA. RP SHAPIRO, CL (reprint author), DANA FARBER CANC INST,DIV MED ONCOL,CTR BREAST EVALUAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 105 TC 5 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1994 VL 8 IS 1 BP 213 EP 231 PG 19 WC Oncology; Hematology SC Oncology; Hematology GA MW742 UT WOS:A1994MW74200015 PM 8150781 ER PT J AU DEMETRI, GD AF DEMETRI, GD TI THE USE OF HEMATOPOIETIC GROWTH-FACTORS TO SUPPORT CYTOTOXIC CHEMOTHERAPY FOR PATIENTS WITH BREAST-CANCER SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; BLOOD PROGENITOR CELLS; RECOMBINANT HUMAN INTERLEUKIN-3; HIGH-DOSE CHEMOTHERAPY; OVARIAN-CANCER; LUNG-CANCER; PHASE-I; GM-CSF; PRIMATES; THERAPY RP DEMETRI, GD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,44 BINNEY ST,BOSTON,MA 02115, USA. NR 74 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1994 VL 8 IS 1 BP 233 EP 249 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA MW742 UT WOS:A1994MW74200016 PM 8150782 ER PT J AU SHAPIRO, CL HENDER, IC AF SHAPIRO, CL HENDER, IC TI BREAST-CANCER - PREFACE SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 UNIV CALIF SAN FRANCISCO,CTR CANC,SAN FRANCISCO,CA 94143. RP SHAPIRO, CL (reprint author), DANA FARBER CANC INST,DIV CLIN ONCOL,CTR BREAST EVALUAT,44 BINNEY ST,BOSTON,MA 02115, USA. 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD FEB PY 1994 VL 8 IS 1 BP R11 EP R12 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA MW742 UT WOS:A1994MW74200001 ER PT J AU MASON, WS CULLEN, J SAPUTELLI, J WU, TT LIU, C LONDON, WT LUSTBADER, E SCHAFFER, P OCONNELL, AP FOUREL, I ALDRICH, CE JILBERT, AR AF MASON, WS CULLEN, J SAPUTELLI, J WU, TT LIU, C LONDON, WT LUSTBADER, E SCHAFFER, P OCONNELL, AP FOUREL, I ALDRICH, CE JILBERT, AR TI CHARACTERIZATION OF THE ANTIVIRAL EFFECTS OF 2' CARBODEOXYGUANOSINE IN DUCKS CHRONICALLY INFECTED WITH DUCK HEPATITIS-B VIRUS SO HEPATOLOGY LA English DT Article ID PEKIN DUCKS; ADENINE-ARABINOSIDE; LIVER-DISEASE; DNA FRAGMENTS; REPLICATION; HEPADNAVIRUS; INVIVO; SERUM; CELLS; INTERFERON AB This study was carried out to evaluate benefits and limitations of long-term therapy of hepatitis B virus infections with a nucleoside analog inhibitor of virus replication. The model we used was the domestic duck chronically infected with duck hepatitis B virus by in ovo infection. 2' Carbodeoxyguanosine was used as an inhibitor of viral DNA synthesis. In all animals examined there was a reduction in virus production during therapy. A dose of 2' carbodeoxyguanosine of 10 mu g/kg every other day reduced the number of infected hepatocytes from greater than 95% to 25% to 50% in less than 3 mo, whereas a 10-fold higher dose produced a decline to less than 10%. Histological evaluation revealed mild to moderate liver injury in ducks receiving the higher dose of 2' carbodeoxyguanosine, suggesting that disappearance of infected hepatocytes may have been accelerated by a toxic effect of the drug. Drug treatment did not completely eliminate duck hepatitis B virus from any duck, and replication was restored in all hepatocytes within a few weeks to several months after antiviral therapy was terminated. Our results suggest that elimination of a chronic infection with a single inhibitor of replication may be difficult in a host that lacks an antiviral immune response capable of eliminating at least a portion of the infected hepatocytes and of ultimately producing antibodies capable of neutralizing residual virus. C1 N CAROLINA STATE UNIV,DEPT MICROBIOL PARASITOL & PATHOL,RALEIGH,NC 27606. UNIV PENN,GRAD GRP PATHOL,PHILADELPHIA,PA 19104. VIRA CHEM INC,BOSTON,MA 02115. DANA FARBER CANC CTR,BOSTON,MA 02115. INST MED & VET SCI,DIV MED VIROL,ADELAIDE,SA 5000,AUSTRALIA. RP MASON, WS (reprint author), FOX CHASE CANC CTR,7701 BURHOLME AVE,PHILADELPHIA,PA 19111, USA. FU NCI NIH HHS [CA-06927]; NCRR NIH HHS [RR-05539]; NIAID NIH HHS [AI-18641] NR 34 TC 49 Z9 50 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 FEB PY 1994 VL 19 IS 2 BP 398 EP 411 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MU618 UT WOS:A1994MU61800018 PM 8294097 ER PT J AU RHOADS, DB AF RHOADS, DB TI LIVER GLUT-1 EXPRESSION - AN ENIGMA DEEPENS SO HEPATOLOGY LA English DT Note ID PERIVENOUS HEPATOCYTES; GLUCOSE TRANSPORTER; MODULATION; RATS RP RHOADS, DB (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,TUMOR BIOL LAB,BOSTON,MA 02129, USA. NR 10 TC 2 Z9 2 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 FEB PY 1994 VL 19 IS 2 BP 540 EP 542 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MU618 UT WOS:A1994MU61800036 PM 8294112 ER PT J AU SCHAPIRO, RH AF SCHAPIRO, RH TI ... AND THE BANDS PLAY ON SO HEPATOLOGY LA English DT Note RP SCHAPIRO, RH (reprint author), MASSACHUSETTS GEN HOSP,HARVARD MED SCH,MED ENDOSCOPY UNIT,BOSTON,MA 02114, USA. NR 6 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 FEB PY 1994 VL 19 IS 2 BP 542 EP 543 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MU618 UT WOS:A1994MU61800037 PM 8294113 ER PT J AU ROGERS, SA PODOLSKY, DK AF ROGERS, SA PODOLSKY, DK TI PREDICTING CHOLANGIOCARCINOMA IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS - AN ANALYSIS OF THE SEROLOGICAL MARKER CA 19-9 SO HEPATOLOGY LA English DT Note ID ANTIGEN RP ROGERS, SA (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. NR 9 TC 5 Z9 5 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 1994 VL 19 IS 2 BP 543 EP 545 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA MU618 UT WOS:A1994MU61800038 PM 8294114 ER PT J AU TEPPER, RI MULE, JJ AF TEPPER, RI MULE, JJ TI EXPERIMENTAL AND CLINICAL-STUDIES OF CYTOKINE GENE-MODIFIED TUMOR-CELLS SO HUMAN GENE THERAPY LA English DT Review ID NECROSIS-FACTOR-ALPHA; COLONY-STIMULATING FACTOR; REDUCED TUMORIGENICITY; LYMPHOCYTES-T; MAMMARY ADENOCARCINOMA; COSTIMULATORY SIGNAL; ANTITUMOR-ACTIVITY; INHIBITION INVIVO; RENAL-CANCER; B16 MELANOMA AB Cytokines are key modulators of host immune and inflammatory responses. The expression of cytokine genes by tumor cells as a result of gene transfer has emerged as a novel strategy to augment in vivo host reactivity to various cancers. This review summarizes the knowledge obtained from experimental systems using this strategy and provides information on the current clinical trials employing this approach. In murine model systems, immunization with tumors expressing certain cytokines [e.g., tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-7 (IL-7), and granulocyte-macrophage colony stimulating (GM-CSF)] has demonstrated their ability to promote the generation of tumor-specific cytotoxic T lymphocytes by various mechanisms; in some cases, significant regressions of established microscopic tumor deposits result. Non T cell mechanisms of tumor killing, such as granulocytic inflammatory responses, may also be elicited by the localized elaboration of certain cytokines [e.g., IL4, granulocyte colony-stimulating factor (G-CSF)]. The potency of antitumor immune potentiation by cytokines, however, remains to be established by further animal studies and emerging clinical trials. The genetic modification of tumors for the expression of immunostimulatory gene products holds promise as a new approach for active immunotherapy of cancer and for the isolation of effector cell populations for use in adoptive immunotherapy protocols. C1 SYSTEMIX,DEPT GENE THERAPY,PALO ALTO,CA 94304. RP TEPPER, RI (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,TUMOR BIOL LAB,BLDG 149,13ST ST,BOSTON,MA, USA. NR 89 TC 281 Z9 287 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD FEB PY 1994 VL 5 IS 2 BP 153 EP 164 DI 10.1089/hum.1994.5.2-153 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA MX708 UT WOS:A1994MX70800003 PM 8186297 ER PT J AU ENG, C SMITH, DP MULLIGAN, LM NAGAI, MA HEALEY, CS PONDER, MA GARDNER, E SCHEUMANN, GFW JACKSON, CE TUNNACLIFFE, A PONDER, BAJ AF ENG, C SMITH, DP MULLIGAN, LM NAGAI, MA HEALEY, CS PONDER, MA GARDNER, E SCHEUMANN, GFW JACKSON, CE TUNNACLIFFE, A PONDER, BAJ TI POINT MUTATION WITHIN THE TYROSINE KINASE DOMAIN OF THE RET PROTOONCOGENE IN MULTIPLE ENDOCRINE NEOPLASIA TYPE 2B AND RELATED SPORADIC TUMORS SO HUMAN MOLECULAR GENETICS LA English DT Article ID MEDULLARY-THYROID CARCINOMA; CHROMOSOME-10; PROTOONCOGENE; DELETION; REGION AB The susceptibility loci for the three multiple endocrine neoplasia (MEN) type 2 syndromes have been mapped to the region of chromosome 10q11.2 containing the RET proto-oncogene, which codes for a receptor tyrosine kinase. The majority of MEN 2A and familial medullary thyroid carcinoma results from missense mutations within one of five cysteine codons in the extracellular domain of the RET proto-oncogene. We now report a missense mutation, resulting in the substitution of a threonine for a methionine at codon 918 in the tyrosine kinase catalytic domain, in the germline of 26 of 28 apparently distinct families with MEN 2B. DNA from five of 13 apparently sporadic MTC and one of 12 apparently sporadic phaeochromocytomas harboured a similar mutation, but the correspending germline DNA was wildtype in each case. 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 & CONTRO,BOSTON,MA 02115. UNIV SAO PAULO,FAC MED,DEPT RADIOTERAPIA,DISCIPLINA ONCOL,SAO PAULO,BRAZIL. HANNOVER MED SCH,ABDOMINAL & TRANSPLANTAT CHIRURG KLIN,W-3000 HANNOVER,GERMANY. HENRY FORD HOSP,GENET RES LAB,DETROIT,MI 48202. RI Nagai, Maria/C-6162-2012; OI Nagai, Maria/0000-0002-0728-4937; Tunnacliffe, Alan/0000-0001-8570-125X; Eng, Charis/0000-0002-3693-5145 NR 31 TC 394 Z9 401 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD FEB PY 1994 VL 3 IS 2 BP 237 EP 241 DI 10.1093/hmg/3.2.237 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA MY583 UT WOS:A1994MY58300003 PM 7911697 ER PT J AU RUBENSTEIN, JT AF RUBENSTEIN, JT TI AXON TERMINATION CONDITIONS FOR ELECTRICAL SIMULATION (VOL 40, PG 654, 1993) SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Correction, Addition C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP RUBENSTEIN, JT (reprint author), MASSACHUSETTS EYE & EAR INFIRM,COCHLEAR IMPLANT RES LAB,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD FEB PY 1994 VL 41 IS 2 BP 203 EP 203 PG 1 WC Engineering, Biomedical SC Engineering GA NK914 UT WOS:A1994NK91400015 ER PT J AU KANDIL, O FISHMAN, JA KOZIEL, H PINKSTON, P ROSE, RM REMOLD, HG AF KANDIL, O FISHMAN, JA KOZIEL, H PINKSTON, P ROSE, RM REMOLD, HG TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION OF HUMAN MACROPHAGES MODULATES THE CYTOKINE RESPONSE TO PNEUMOCYSTIS-CARINII SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; LISTERIA-MONOCYTOGENES INFECTION; FACTOR-ALPHA; SURFACE GLYCOPROTEIN; ALVEOLAR MACROPHAGES; SALMONELLA INFECTION; GAMMA INTERFERON; HOST-RESISTANCE; CELLS; INTERLEUKIN-6 AB The present studies examined production of the cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 by human monocyte-derived macrophages exposed to Pneumocystis carinii in vitro and the impact of concurrent macrophage infection with human immunodeficiency virus type 1 (HIV-1) on these cytokine responses. Macrophages were infected with the HIV-1 Bat monocytotropic strain for 10 to 14 days and then exposed to P. carinii. At various times following P. carinii treatment, culture supernatants were harvested to assess the cytokine profile. Addition of P. carinii to HIV-uninfected macrophages resulted in augmented production of IL-6, TNF-alpha, and IL-1 beta protein. By contrast, in HIV-infected macrophages exposed to P. carinii, only the release of IL-6 was increased compared with that for HIV-uninfected macrophages, while the levels of TNF-alpha and IL-1 beta decreased. This altered response was confirmed at the molecular level for TNF-alpha mRNA. Preventing physical contact between P. carinii and macrophages by a membrane filter inhibited all cytokine release. Substituting P. carinii with a preparation of P. carinii 95- to 115-kDa major membrane glycoprotein A yielded a response similar to that obtained by addition of intact P. carinii. These results suggest that HIV-1 infection of human macrophages modulates cytokine responses to P. carinii. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. RP KANDIL, O (reprint author), NEW ENGLAND DEACONESS HOSP,DIV PULM & CRIT MED,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [P01 HL 43510, K08 HL 01916] NR 42 TC 36 Z9 39 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 FEB PY 1994 VL 62 IS 2 BP 644 EP 650 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MR841 UT WOS:A1994MR84100041 PM 8300221 ER PT J AU GUO, YJ LIN, SC WANG, JH BIGBY, M SY, MS AF GUO, YJ LIN, SC WANG, JH BIGBY, M SY, MS TI PALMITOYLATION OF CD44 INTERFERES WITH CD3-MEDIATED SIGNALING IN HUMAN T-LYMPHOCYTES SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD3; CD44; LYMPHOCYTES; PALMITOYLATION ID CELL ACTIVATION; TRANSMEMBRANE GLYCOPROTEIN; MONOCLONAL-ANTIBODY; TRANSFERRIN RECEPTOR; HOMING RECEPTOR; PROTEIN-KINASE; FATTY-ACID; ACYLATION; MOLECULE; PGP-1 AB We studied the interactions between CD44 and four different monoclonal anti-CD44 antibodies. All four monoclonal anti-CD44 antibodies studied (P3H9, Bu52, IM.7, and GKW.A3) act in synergy with human anti-CD2 antibodies in stimulating normal human peripheral blood lymphocytes to proliferate. GKW.A3 and IM.7 but not P3H9 or Bu52 inhibited the proliferation of normal human peripheral blood lymphocytes stimulated by anti-CD3. Interestingly, only GKW.A3 and IM.7 stimulated the incorporation of [H-3]palmitic acid and palmitoylation of CD44 molecules by normal human peripheral blood lymphocytes. The two monoclonal anti-CD44 antibodies (P3H9 and Bu52) that failed to inhibit anti-CD3 induced proliferation also failed to induce the incorporation of [H-3]palmitic acid. More importantly, the inhibitory effects of GKW.A3 were reversed in the presence of cerulenin, an inhibitor of protein palmitoylation. Therefore, palmitoylation of CD44 may interfere with anti-CD3 mediated signaling pathways. These data support the hypothesis that palmitoylation of cell surface receptors may play an active role in receptor and receptor interactions and signal transduction in normal human T lymphocytes. C1 CASE WESTERN RESERVE UNIV,SCH MED,INST PATHOL,DEPT PATHOL,BIOMED RES BLDG,10900 EUCLID AVE,CLEVELAND,OH 44106. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIAID NIH HHS [R0-1 AI 27740]; NIAMS NIH HHS [AR-38018] NR 50 TC 26 Z9 26 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD FEB PY 1994 VL 6 IS 2 BP 213 EP 221 DI 10.1093/intimm/6.2.213 PG 9 WC Immunology SC Immunology GA MW888 UT WOS:A1994MW88800005 PM 7512372 ER PT J AU SCHILLER, JH SABATINI, L BITTNER, G PINKERMAN, CL MAYOTTE, J LEVITT, M MEISNER, L AF SCHILLER, JH SABATINI, L BITTNER, G PINKERMAN, CL MAYOTTE, J LEVITT, M MEISNER, L TI PHENOTYPIC, MOLECULAR AND GENETIC-CHARACTERIZATION OF TRANSFORMED HUMAN BRONCHIAL EPITHELIAL-CELL STRAINS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE TRANSFORMATION; HUMAN BRONCHIAL EPITHELIAL CELLS ID RAS ONCOGENE ACTIVATION; LUNG-CANCER PATIENTS; SQUAMOUS DIFFERENTIATION; NEOPLASTIC PROGRESSION; CLINICAL-SIGNIFICANCE; PROGNOSTIC MARKER; P53 MUTATIONS; RETINOIC ACID; LINES; ADENOCARCINOMA AB In order to study the phenotypic, genetic, and molecular characteristics of normal human bronchial epithelial cells (HBE) so as to establish a model of HBE cell carcinogenesis, we established six HBE cell strains by transfection with either the SV40 virus or an origin of replication defective large T plasmid. Tracheobronchial specimens were obtained from autopsy samples or heart donors from noncancer patients, cultured, and transfected using strontium chloride. Three cell strains were established by transfection with the whole SV40 virus (NL4SV, NL11SV, and NL20SV) and three cell strains were established with the origin of replication depleted T antigen (NL25, NL30-0, NL30-N). All of the cell strains senesced between passages 19-28. None of the cell strains formed colonies in 0.15% agarose. All required epidermal growth factor, whereas their requirement for fetal bovine serum was variable. None of the cell strains formed tumors in nude mice. Cytogenetic analysis revealed that none of the cell strains were diploid. They ranged from having few random changes to extreme chromosomal instability. Only one cell strain (NL30-N) had two consistent markers. About one-third of the NL30-O cells, derived from independent cultures from the same donor, had the same markers. No DNA amplification for c-myc was observed in any of the transformed HBE cell strains. No mutations were detected in K-ras codons 12, 13, and 61 using primer engineered restriction fragment-length polymorphism analysis. No mutations were detected in exons 5-9 of the p53 gene by single strand conformation polymorphism (SSCP) analysis. We conclude that despite differences in morphology, phenotype, differentiation, and karyotype between six nontumorigenic HBE cell strains, none have activation of dominant oncogenes or inactivation of tumor suppressor genes that have been described in human lung tumors. These cells should be useful as a model for molecular studies of HBE cell carcinogenesis. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53792. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53792. UNIV WISCONSIN HOSP & CLIN,DEPT PATHOL & LAB MED,MADISON,WI 53792. UNIV PITTSBURGH,PITTSBURGH,PA 15260. NR 59 TC 4 Z9 4 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 1994 VL 4 IS 2 BP 461 EP 470 PG 10 WC Oncology SC Oncology GA MT110 UT WOS:A1994MT11000026 PM 21566947 ER PT J AU WEISSMANN, D LEWANDROWSKI, K GODINE, J CENTENO, B WARSHAW, A AF WEISSMANN, D LEWANDROWSKI, K GODINE, J CENTENO, B WARSHAW, A TI PANCREATIC CYSTIC ISLET-CELL TUMORS - CLINICAL AND PATHOLOGICAL FEATURES IN 2 CASES WITH CYST FLUID ANALYSIS SO INTERNATIONAL JOURNAL OF PANCREATOLOGY LA English DT Note DE PANCREAS; ISLET-CELL TUMOR; CYSTIC TUMOR; TUMOR MARKERS ID CARCINOEMBRYONIC ANTIGEN; NEOPLASMS; CYSTADENOCARCINOMA; CYSTADENOMA; DIAGNOSIS; LESIONS AB Cystic islet-cell tumors are rare neoplasms that may be confused with more familiar cystic pancreatic lesions, such as pseudocysts, serous cystadenoma, and mucinous tumors. Analysis of aspirated cyst fluid for tumor markers (carcinoembryonic antigen [CEA], CA-125, and CA-15.3), enzymes (amylase and lipase), viscosity, and cytology has been proposed as an aid to preoperative differential diagnosis. These tests will distinguish mucinous from nonmucinous cysts and usually help in determining malignancy. However, cyst fluid parameters from rarer types of pancreatic cystic tumors have not been described. We report the clinical and pathologic features of two cystic islet-cell tumors including cyst fluid parameters in one of the cases. Two cases of cystic islet-cell tumors were identified by clinical history, histopathologic, and immunohistochemical techniques. Cyst fluid was aspirated intraoperatively from one case and analyzed for CEA, CA-125, CA 15.3, insulin, amylase, viscosity, and cytology. Cyst fluid analysis showed low values for CEA, CA-125, and CA-15.3, low viscosity, and variable amylase content. This spectrum of findings is similar to that of serous cystadenomas. Cyst fluid cytologic examination was positive for neuroendocrine-type epithelial cells and insulin levels were elevated, observations indicative of an islet-cell tumor. Analysis of fluid from cystic islet-cell tumors may aid in the preoperative differentiation of these tumors from more common pancreatic cystic lesions. These findings represent the first report of the characteristics of the fluid in these uncommon tumors. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 19 TC 15 Z9 15 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 FEB PY 1994 VL 15 IS 1 BP 75 EP 79 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA MX551 UT WOS:A1994MX55100009 PM 8195644 ER PT J AU BERRA, A DUTT, JE NOURI, M FOSTER, CS AF BERRA, A DUTT, JE NOURI, M FOSTER, CS TI HEAT-SHOCK PROTEIN EXPRESSION IN HUMAN CONJUNCTIVA SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE HEAT SHOCK PROTEIN; GAMMA/DELTA T CELL; OCULAR CICATRICIAL PEMPHIGOID; AUTOIMMUNITY; CONJUNCTIVA ID T-CELL RECEPTOR; SYNOVIAL-FLUID; RHEUMATOID-ARTHRITIS; REGULATED PROTEIN; LYMPHOCYTES; RECOGNITION; ANTIGEN; ANTIBODIES; CLONES; HSP70 AB Purpose. To examine the distribution of human heat shock proteins (HSPs) HSP90, inducible HSP70 (iHSP70), constitutive and inducible HSP70 (cHSP70), HSP65, and human HSP27 in conjunctival biopsy specimens of ocular cicatricial pemphigoid (OCP), atopic keratoconjunctivitis, and healthy persons with cataract. Methods. Using an immunoperoxidase technique, conjunctival biopsy specimens from ten patients with ocular cicatricial pemphigoid, ten patients with atopic keratoconjunctivitis and ten healthy persons undergoing cataract surgery were analyzed with a panel of monoclonal antibodies directed against human HSPs. Results. Large amounts of HSP90 and HSP27, and lesser amounts of cHSP70, iHSP70, and HSP65 were present in atopic keratoconjunctivitis and normal epithelium; less of these proteins were seen in OCP conjunctival epithelium. In atopic keratoconjunctivitis and normal tissue the substantia propria contained a few HSP-positive cells, and the vascular endothelium was consistently negative for all of the HSPs. In sharp contrast, OCP stroma contained large numbers of cells staining for HSP27, HSP90, and iHSP70, and the vasculature was strongly positive, particularly for HSP90, cHSP70, and HSP27. Conclusion. These results indicate that normal and atopic keratoconjunctivitis epithelia express HSP90 and HSP27 and some form of HSP65 and HSP70. The differences between normal, atopic keratoconjunctivitis, and OCP stromal staining suggest an upregulated expression of HSP90, cHSP70, and HSP27 at the site of inflammation in OCP, the stroma, from cytokine release. The striking presence of HSP in the conjunctival vascular endothelium from OCP patients suggests a previously unappreciated role of the vasculature in OCP. C1 MASSACHUSETTS EYE & EAR INFIRM,HARVARD MED SCH,HILLES IMMUNOL LAB,BOSTON,MA 02114. NR 29 TC 12 Z9 13 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 FEB PY 1994 VL 35 IS 2 BP 352 EP 357 PG 6 WC Ophthalmology SC Ophthalmology GA MY957 UT WOS:A1994MY95700005 PM 8112980 ER PT J AU ANDLEY, UP LEWIS, RM REDDAN, JR KOCHEVAR, IE AF ANDLEY, UP LEWIS, RM REDDAN, JR KOCHEVAR, IE TI ACTION SPECTRUM FOR CYTOTOXICITY IN THE UVA-WAVELENGTH AND UVB-WAVELENGTH REGION IN CULTURED LENS EPITHELIAL-CELLS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE ACTION SPECTRUM; LENS EPITHELIAL CELLS; UV RADIATION; CELL KILLING; CATARACT ID NEAR-ULTRAVIOLET RADIATION; HUMAN-LYMPHOBLASTOID CELLS; B RADIATION; DNA DAMAGE; CATARACT; LIGHT; INDUCTION; EXPOSURE; MUTATION; REPAIR AB Purpose. This study was done to quantitate the biologic effects of different wavelengths of radiation in the UVA- and UVB-wavelength region on cultured rabbit lens epithelial cells. Methods. An action spectrum for UV-induced cytotoxicity as measured by colony-forming ability was determined using six different monochromatic wavelengths from 297 to 405 nm in rabbit lens epithelial cell line N/N1003A. Cell survival was determined by clonogenic assay. Fluence rates were monitored with a calibrated radiometer. Results. Survival curves show that cell killing was most efficient at 297 nm. After quantum correction, the efficiency of 297-nm radiation in cell killing was 7 times greater than was 302-nm radiation. Radiation at 297 nm was more than 170, 340, 560, and 2000 times as effective in cell killing as 313-, 325-, 334-, and 365-nm radiation, respectively. The action spectrum had a shape similar to the DNA absorption spectrum in the UVB region, suggesting that DNA may be one of the critical targets for damage to the cells. At wavelengths longer than 313 nm, the shape of the action spectrum deviated from the DNA absorption spectrum. Conclusions. Cytotoxicity of UV radiation in cultured lens epithelial cells varies greatly with wavelength within the UVA and UVB regions. Different mechanisms may predominate in the two wavelength regions. Cultured cells may provide a suitable system for investigating the mechanisms by which UV radiation damages lens epithelial cells and leads to cataract formation. C1 OAKLAND UNIV,DEPT BIOL SCI,ROCHESTER,MI. MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RP ANDLEY, UP (reprint author), WASHINGTON UNIV,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,660 S EUCLID AVE,CAMPUS BOX 8096,ST LOUIS,MO 63110, USA. FU NEI NIH HHS [EY05681, EY00362] NR 39 TC 56 Z9 59 U1 0 U2 3 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 FEB PY 1994 VL 35 IS 2 BP 367 EP 373 PG 7 WC Ophthalmology SC Ophthalmology GA MY957 UT WOS:A1994MY95700008 PM 8112983 ER PT J AU HETH, CA MARESCALCHI, PA AF HETH, CA MARESCALCHI, PA TI INOSITOL TRIPHOSPHATE GENERATION IN CULTURED RAT RETINAL-PIGMENT EPITHELIUM SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 1992 CL SARASOTA, FL SP ASSOC RES VIS & OPHTHALMOL DE RETINAL PIGMENT EPITHELIUM; ROYAL COLLEGE OF SURGEONS RAT; PHAGOCYTOSIS; ROD OUTER SEGMENTS; INOSITOL TRIPHOSPHATE ID ROD OUTER SEGMENTS; MUSCARINIC RECEPTOR STIMULATION; KINASE-C ACTIVATION; PROTEIN-PHOSPHORYLATION; 2ND MESSENGERS; PAROTID-GLANDS; RCS-RAT; CELLS; PHAGOCYTOSIS; DIACYLGLYCEROL AB Purpose. To evaluate the generation of the second messenger molecule inositol triphosphate (IP3) in response to phagocytic challenge in cultures of retinal pigment epithelium (RPE) prepared from normal Long Evans or dystrophic Royal College of Surgeons (RCS) rats. Methods. RPE cultures were phagocytically challenged with isolated rat rod outer segments (ROS) or polystyrene latex spheres (PSL). Carbachol was added to some cultures as a positive control to stimulate the IP3 pathway. Inositol triphosphate levels in RPE cells were analyzed by high-pressure liquid chromatography and radioreceptor assay. Incorporation of H-3-myoinositol into phosphatidylinositol lipids was analyzed by thin layer chromatography and autoradiography. RP HETH, CA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,HARVARD MED SCH,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EYO8091] NR 37 TC 29 Z9 29 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 FEB PY 1994 VL 35 IS 2 BP 409 EP 416 PG 8 WC Ophthalmology SC Ophthalmology GA MY957 UT WOS:A1994MY95700013 PM 8112988 ER PT J AU TRUJILLO, JR NAVIA, B MCLANE, MF WORTH, JL LEE, TH ESSEX, M AF TRUJILLO, JR NAVIA, B MCLANE, MF WORTH, JL LEE, TH ESSEX, M TI EVALUATION OF AUTOANTIBODIES TO BRAIN PROTEINS IN PATIENTS WITH AIDS DEMENTIA COMPLEX SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE AIDS DEMENTIA COMPLEX; AUTOANTIBODIES; BRAIN ANTIGEN ID CEREBROSPINAL-FLUID; ANTI-HIV; ANTIBODIES; INFECTION AB A high frequency of autoantibodies to brain proteins has been reported in HIV-1-positive patients. However, the specificity of this response has not been characterized. Using homogenized tissue from three normal brains, the presence of autoantibodies to human brain proteins was analyzed in 16 HIV-1-positive patients with AIDS dementia complex (ADC), 10 HIV-1-positive patients without ADC, 10 patients with multiple sclerosis, 10 patients with juvenile rheumatoid arthritis, and 10 normal controls. Although antibodies to various brain proteins were detected in sera from one-third of HIV-1-infected individuals with or without ADC, the proteins recognized were different among different brains. Only one ADC patient had consistent seroreactivity to a 50-kDa brain-specific protein. Our results indicate that autoantibodies to brain proteins are infrequently present in patients with ADC. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA39805]; NHLBI NIH HHS [HL33774] NR 25 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD FEB PY 1994 VL 7 IS 2 BP 103 EP 108 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MW114 UT WOS:A1994MW11400001 PM 8301522 ER PT J AU SIMON, BA VENEGAS, JG AF SIMON, BA VENEGAS, JG TI ANALYZING (NN)-N-13 LUNG WASHOUT CURVES IN THE PRESENCE OF INTRAREGIONAL NONUNIFORMITIES SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE POSITRON IMAGING; LUNG IMAGING; REGIONAL VENTILATION; AIR TRAPPING ID HIGH-FREQUENCY VENTILATION; POSITRON EMISSION TOMOGRAPHY; GAS-TRANSPORT; REGIONAL VENTILATION; N-13; MODEL AB The use of (NN)-N-13 and positron imaging provides a powerful noninvasive means of assessing regional pulmonary function. Current techniques for analyzing lung washout curves, however, are subject to error due to intraregional nonuniformities, particularly in the presence of areas with very long time constants or gas trapping. This paper presents a simple ''hybrid'' method for analyzing (NN)-N-13-washout studies that addresses the problems of regions of air trapping and long time constants within a region of interest. This method assumes an exponential washout form for the slow regions, estimates their fractional volume, and subtracts their contribution from the overall washout curve. The modified Stewart-Hamilton method is then applied to the remaining washout curve to calculate its ventilation. The overall specific ventilation of the region is calculated as the volume weighted average of the specific ventilations of the two compartments. The performance of the hybrid method is compared with other currently used correction techniques by using a simulated two-compartment lung washout in which there is a variable amount of gas trapping. The analysis techniques are also applied to washout data with intraregional nonuniformities obtained during experimentally created unilateral bronchial obstruction. This new approach has the advantages of automatically correcting for washout truncation, estimating the relative size of the trapped or slow region while eliminating its bias on the regional ventilation, and yet retaining the unrestricted and robust nature of the Stewart-Hamilton method in the analysis of the well-ventilated regions. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT BIOMED ENGN,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-38267] NR 19 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD FEB PY 1994 VL 76 IS 2 BP 956 EP 964 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA MX610 UT WOS:A1994MX61000063 PM 8175611 ER PT J AU PASTER, BJ DEWHIRST, FE OLSEN, I FRASER, GJ AF PASTER, BJ DEWHIRST, FE OLSEN, I FRASER, GJ TI PHYLOGENY OF BACTEROIDES, PREVOTELLA, AND PORPHYROMONAS SPP AND RELATED BACTERIA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DEOXYRIBONUCLEIC-ACID HOMOLOGIES; RIBOSOMAL-RNA SEQUENCES; GENUS BACTEROIDES; SP-NOV; STRAINS; MELANINOGENICUS; PROPOSAL; TAXONOMY; FRAGILIS AB The phylogenetic structure of the bacteroides subgroup of the cytophaga-flavobacter-bacteroides (CFB) phylum was examined by 16S rRNA sequence comparative analysis. Approximately 95% of the 16S rRNA sequence was determined for 36 representative strains of species of Prevotella, Bacteroides, and Porphyromonas and related species by a modified Sanger sequencing method. A phylogenetic tree was constructed from a corrected distance matrix by the neighbor-joining method, and the reliability of tree branching,vas established by bootstrap analysis. The bacteroides subgroup was divided primarily into three major phylogenetic clusters which contained most of the species examined. The first cluster, termed the prevotella cluster, was composed of 16 species of Prevotella, including P. melaninogenica, P. intermedia, P. nigrescens, and the ruminal species P. ruminicola. Two oral species, P. zoogleoformans and P. heparinolytica, which had been recently placed in the genus Prevotella, did not fall within the prevotella cluster. These two species and six species of Bacteroides, including the type species B. fragilis, formed the second cluster, termed the bacteroides cluster. The third cluster, termed the porphyromonas cluster, was divided into two subclusters. The first contained Porphyromonas gingivalis, P. endodontalis, P. asaccharolytica, P. circumdentaria, P. salivosa, [Bacteroides] levii (the brackets around genus are used to indicate that the species does not belong to the genus by the sensu stricto definition), and [Bacteroides] macacae, and the second subcluster contained [Bacteroides] forsythus and [Bacteroides] distasonis. [Bacteroides] splanchnicus fell just outside the three major clusters but still belonged within the bacteroides subgroup. On the basis of bootstrap analysis, the remaining species, [Bacteroides] putredinis, Rikenella microfusus, and two misclassified, free-living species of Cytophaga, appeared to form an additional subgroup separate from the. bacteroides and other subgroups of the CFB phylum. However, on classification by single-base signatures, these species belonged within the bacteroides subgroup. Additional single-base signatures defined and differentiated clads within the bacteroides subgroup. With few exceptions, the 16S rRNA data were in overall agreement with previously proposed reclassifications of species of Bacteroides, Prevotella, and Polphyromonas. Suggestions are made to accommodate those species which do not fit previous reclassification schemes. C1 UNIV OSLO,FAC DENT,DEPT ORAL BIOL,OSLO,NORWAY. RP PASTER, BJ (reprint author), FORSYTH DENT CTR,DEPT MOLEC GENET,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04881, DE-08303] NR 38 TC 157 Z9 158 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 1994 VL 176 IS 3 BP 725 EP 732 PG 8 WC Microbiology SC Microbiology GA MU151 UT WOS:A1994MU15100022 PM 8300528 ER PT J AU VENUGOPALAN, V NISHIOKA, NS MIKIC, BB AF VENUGOPALAN, V NISHIOKA, NS MIKIC, BB TI THE EFFECT OF LASER PARAMETERS ON THE ZONE OF THERMAL-INJURY PRODUCED BY LASER-ABLATION OF BIOLOGICAL TISSUE SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID CARBON-DIOXIDE LASER; CONTINUOUS-WAVE CO2-LASER; 3-ZONE MODEL; DAMAGE; SKIN; INCISIONS; SURGERY; BENEATH AB A thermal model to predict the effect of laser parameters on the zone of thermal injury produced by laser ablation of biological tissue is presented. The model suggests that the Peclet number based on the optical penetration depth of laser radiation is the key parameter in determining the resulting zone of thermal injury. We show that the zone of thermal injury is minimized for Peclet numbers greater than one since the transport of energy via conduction beyond the ablation front is minimized. We also show that for Peclet numbers less than one, larger zones of thermal damage are unavoidable regardless of the laser pulse duration. The predictions of the model are compared with data available in the literature. Deviations between the model predictions and published data are discussed and the potential effects of the model assumptions, optical scattering, pyrolysis, temporal pulse shape, pulse duration, irradiance and pulse repetition rate are explored. C1 MIT,DEPT MECH ENGN,CAMBRIDGE,MA 02139. RP VENUGOPALAN, V (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 35 TC 29 Z9 29 U1 2 U2 3 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD FEB PY 1994 VL 116 IS 1 BP 62 EP 70 DI 10.1115/1.2895706 PG 9 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA MZ750 UT WOS:A1994MZ75000009 PM 8189716 ER PT J AU MARR, DS ROSENTHAL, DI COHEN, GL TOMFORD, WW AF MARR, DS ROSENTHAL, DI COHEN, GL TOMFORD, WW TI RAPID POSTOPERATIVE OSTEOLYSIS IN PAGET DISEASE - A CASE-REPORT SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Note ID BONE C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP MARR, DS (reprint author), MASSACHUSETTS GEN HOSP,WANG AMBULATORY CARE CTR,DEPT RADIOL,SUITE 515,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 14 TC 11 Z9 12 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 1994 VL 76A IS 2 BP 274 EP 277 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA MZ270 UT WOS:A1994MZ27000017 PM 8113265 ER PT J AU CHEN, TH PRATT, SA SHOBACK, DM AF CHEN, TH PRATT, SA SHOBACK, DM TI INJECTION OF BOVINE PARATHYROID POLY(A)(+) RNA INTO XENOPUS-OOCYTES CONFERS SENSITIVITY TO HIGH EXTRACELLULAR CALCIUM SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID INOSITOL PHOSPHATES; HORMONE SECRETION; MOLECULAR-CLONING; DIVALENT-CATIONS; CYTOSOLIC CA-2+; MESSENGER-RNA; CELLS; RECEPTOR; EXPRESSION; ACCUMULATION AB Parathyroid cells detect increments in the extracellular [Ca2+], which lead to substantial increases in intracellular free Ca2+ ([Ca2+](i)) and, ultimately, to suppression of parathyroid hormone (PTH) secretion. To determine whether mRNA from parathyroid tissue could confer sensitivity to high extracellular Ca2+, we isolated and injected total bovine parathyroid poly(A)(+) RNA into Xenopus laevis oocytes. To assess translational activity of the RNA, PTH released into the media was measured. Intact PTH was detected in the medium for less than or equal to 48 h, and injection of increasing amounts of RNA (similar to 0.5-50 ng/oocyte) led to the release of greater quantities of PTH. We screened for the expression of a putative Ca2+ sensor molecule by measuring Ca-45 efflux from preloaded oocytes, in response to raising extracellular [Ca2+] from 0.7 to 5.7 mM. This increment in [Ca2+] stimulated Ca-45 efflux by 249 +/- 52 cpm over 20 min from eggs injected with parathyroid poly(A)(+) RNA (n = 22). This response was significantly greater than Ca-45 efflux from any group of controls exposed to the same change in extracellular Ca2+ (p < 0.02), including oocytes injected with either water, cRNA for the platelet-derived growth factor (PDGF) BB receptor, or T cell poly(A)(+) RNA. Size-fractionation of poly(A)(+) RNA over sucrose gradients demonstrated that mRNA, which induced responsiveness to high extracellular Ca2+ was present in fractions with transcripts of similar to 5-9 kB. Injection of these fractions also conferred sensitivity to the presence of Ba2+ or Sr2+ (both at 5 mM) in the media. These findings establish that parathyroid cells express mRNA for a molecule capable of detecting changes in the extracellular divalent cation concentration. This molecule may play a role in secretory responses mediated by Ca2+ in the parathyroid. C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO VA MED CTR,ENDOCRINE RES UNIT,SAN FRANCISCO,CA 94121. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA. FU NIDDK NIH HHS [R29 DK39594, DK43400] NR 30 TC 13 Z9 13 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 FEB PY 1994 VL 9 IS 2 BP 293 EP 300 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MW246 UT WOS:A1994MW24600018 PM 7511319 ER PT J AU VANETTEN, RA JACKSON, PK BALTIMORE, D SANDERS, MC MATSUDAIRA, PT JANMEY, PA AF VANETTEN, RA JACKSON, PK BALTIMORE, D SANDERS, MC MATSUDAIRA, PT JANMEY, PA TI THE COOH TERMINUS OF THE C-ABL TYROSINE KINASE CONTAINS DISTINCT F-ACTIN AND G-ACTIN BINDING DOMAINS WITH BUNDLING ACTIVITY SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CROSS-LINKING; V-ABL; ALPHA-ACTININ; GENE-PRODUCT; PROTEIN; CELLS; POLYMERIZATION; SEQUENCES; GELSOLIN; TRANSFORMATION AB The myristoylated form of c-Abl protein, as well as the P210bcr/abl protein, have been shown by indirect immunofluorescence to associate with F-actin stress fibers in fibroblasts. Analysis of deletion mutants of c-Abl stably expressed in fibroblasts maps the domain responsible for this interaction to the extreme COOH-terminus of Abl. This domain mediates the association of a heterologous protein with F-actin filaments after microinjection into NIH 3T3 cells, and directly binds to F-actin in a cosedimentation assay. Microinjection and cosedimentation assays localize the actin-binding domain to a 58 amino acid region, including a charged motif at the extreme COOH-terminus that is important for efficient binding. F-actin binding by Abl is calcium independent, and Abl competes with gelsolin for binding to F-actin. In addition to the F-actin binding domain, the COOH-terminus of Abl contains a proline-rich region that mediates binding and sequestration of G-actin, and the Abl F- and G-actin binding domains cooperate to bundle F-actin filaments in vitro. The COOH terminus of Abl thus confers several novel localizing functions upon the protein, including actin binding, nuclear localization, and DNA binding. Abl may modify and receive signals from the F-actin cytoskeleton in vivo, and is an ideal candidate to mediate signal transduction from the cell surface and cytoskeleton to the nucleus. C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. ROCKEFELLER UNIV,NEW YORK,NY 10021. BRIGHAM & WOMENS HOSP,DEPT MED,DIV EXPTL MED,BOSTON,MA 02115. RP VANETTEN, RA (reprint author), HARVARD UNIV,SCH MED,DEPT GENET,CTR BLOOD RES,200 LONGWOOD AVE,BOSTON,MA 02115, USA. RI Matsudaira, Paul/H-1475-2012 OI Matsudaira, Paul/0000-0002-8399-3276 FU NCI NIH HHS [CA51462]; NIAMS NIH HHS [AR38910]; NIDDK NIH HHS [DK35306] NR 71 TC 235 Z9 235 U1 1 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 FEB PY 1994 VL 124 IS 3 BP 325 EP 340 DI 10.1083/jcb.124.3.325 PG 16 WC Cell Biology SC Cell Biology GA MT699 UT WOS:A1994MT69900010 PM 8294516 ER PT J AU OSBORN, L VASSALLO, C BROWNING, BG TIZARD, R HASKARD, DO BENJAMIN, CD DOUGAS, I KIRCHHAUSEN, T AF OSBORN, L VASSALLO, C BROWNING, BG TIZARD, R HASKARD, DO BENJAMIN, CD DOUGAS, I KIRCHHAUSEN, T TI ARRANGEMENT OF DOMAINS, AND AMINO-ACID-RESIDUES REQUIRED FOR BINDING OF VASCULAR CELL-ADHESION MOLECULE-1 TO ITS COUNTER-RECEPTOR VLA-4 (ALPHA-4-BETA-1) SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INTEGRIN VLA-4; LYMPHOCYTE ADHERENCE; SPLICED DOMAIN; FIBRONECTIN; CLONING; IMMUNOGLOBULIN; ICAM-1; VCAM-1; SITE; ENDOTHELIUM AB Interaction of the vascular cell adhesion molecule (VCAM-1) with its counter-receptor very late antigen-4 (VLA-4) (integrin alpha(4) beta(1)) is important for a number of developmental pathways and inflammatory functions. We are investigating the molecular mechanism of this binding, in the interest of developing new anti-inflammatory drugs that block it. In a previous report, we showed that the predominant form of VCAM-1 on stimulated endothelial cells, seven-domain VCAM (VCAM-7D), is a functionally bivalent molecule. One binding site requires the first and the other requires the homologous fourth immunoglobulin-like domain. Rotary shadowing and electron microscopy of recombinant soluble VCAM-7D molecules suggests that the seven Ig-Iike domains are extended in a slightly bent linear array, rather than compactly folded together. We have systematically mutagenized the first domain of VCAM-6D (a monovalent, alternately spliced version missing domain 4) by replacing 3-4 amino acids of the VCAM sequence with corresponding portions of the related ICAM-1 molecule. Specific amino acids important for binding VLA-4 include aspartate 40 (D40), which corresponds to the acidic ICAM-1 residue glutamate 34 (E34) previously reported to be essential for binding of ICAM-1 to its integrin counter-receptor LFA-1. A small region of VCAM including D40 QIDS, can be replaced by the similar ICAM-1 sequence, GIET, without affecting function or epitopes, indicating that this region is part of a general integrin-binding structure rather than a determinant of binding specificity for a particular integrin. The VCAM-1 sequence G65NEH also appears to be involved in binding VLA-4. C1 HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT MED,RHEUMATOL UNIT,LONDON W12 0NN,ENGLAND. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA. CTR BLOOD RES,BOSTON,MA 02115. RP OSBORN, L (reprint author), BIOGEN INC,14 CAMBRIDGE CTR,CAMBRIDGE,MA 02142, USA. NR 35 TC 145 Z9 147 U1 0 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 FEB PY 1994 VL 124 IS 4 BP 601 EP 608 DI 10.1083/jcb.124.4.601 PG 8 WC Cell Biology SC Cell Biology GA MW691 UT WOS:A1994MW69100018 PM 7508942 ER PT J AU KANSAS, GS SAUNDERS, KB LEY, K ZAKRZEWICZ, A GIBSON, RM FURIE, BC FURIE, B TEDDER, TF AF KANSAS, GS SAUNDERS, KB LEY, K ZAKRZEWICZ, A GIBSON, RM FURIE, BC FURIE, B TEDDER, TF TI A ROLE FOR THE EPIDERMAL GROWTH FACTOR-LIKE DOMAIN OF P-SELECTIN IN LIGAND RECOGNITION AND CELL-ADHESION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; GRANULE MEMBRANE-PROTEIN; LEUKOCYTE-ADHESION; ACTIVATED PLATELETS; COFACTOR ACTIVITY; MONOCLONAL-ANTIBODY; CARBOHYDRATE LIGAND; MOLECULE-1 ELAM-1; SURFACE MOLECULE; LECTIN ACTIVITY AB The selectin family of adhesion molecules mediates the initial interactions of leukocytes with endothelium. The extracellular region of each selectin contains an amino-terminal C-type lectin domain, followed by an EGF-like domain and multiple short consensus repeat units (SCR). Previous studies have indirectly suggested a role for each of the extracellular domains of the selectins in cell adhesion. In this study, a panel of chimeric selectins created by exchange of domains between L- and P-selectin was used to directly examine the role of the extracellular domains in cell adhesion. Exchange of only the lectin domains between L- and P-selectin conferred the adhesive and ligand recognition functions of the lectin domain of the parent molecule. However, chimeric selectins which contained both the lectin domain of L-selectin and the EGF-like domain of P-selectin exhibited dual ligand-binding specificity. These chimeric proteins supported adhesion both to myeloid cells and to high endothelial venules (HEV) of lymph nodes and mesenteric venules in vivo. Exchange of the SCR domains had no detectable effect on receptor function or specificity. Thus, the EGF-like domain of P-selectin may play a direct role in ligand recognition and leukocyte adhesion mediated by P-selectin, with the lectin plus EGF-like domains collectively forming a functional ligand recognition unit. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. FREE UNIV BERLIN,INST PHYSIOL,BERLIN,GERMANY. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA. FU NCI NIH HHS [CA-26872, CA-54464]; NIAID NIH HHS [AI-26872] NR 69 TC 113 Z9 116 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 FEB PY 1994 VL 124 IS 4 BP 609 EP 618 DI 10.1083/jcb.124.4.609 PG 10 WC Cell Biology SC Cell Biology GA MW691 UT WOS:A1994MW69100019 PM 7508943 ER PT J AU SCHOENENBERGER, CA ZUK, A ZINKL, GM KENDALL, D MATLIN, KS AF SCHOENENBERGER, CA ZUK, A ZINKL, GM KENDALL, D MATLIN, KS TI INTEGRIN EXPRESSION AND LOCALIZATION IN NORMAL MDCK CELLS AND TRANSFORMED MDCK CELLS LACKING APICAL POLARITY SO JOURNAL OF CELL SCIENCE LA English DT Article DE EPITHELIAL POLARITY; INTEGRIN; MDCK ID CANINE KIDNEY-CELLS; LAMININ RECEPTOR; ADHESION RECEPTORS; EPITHELIAL-CELLS; COLLAGEN RECEPTOR; MEMBRANE POLARITY; BINDING; PROTEIN; ALPHA-6-BETA-4; SUBUNITS AB Epithelial cells polarize in response to contacts with the extracellular matrix and with neighboring cells. Interactions of cells with the extracellular matrix are mediated mainly by the integrin family of receptors. To begin to understand the role of integrins in polarization, we have investigated the expression and localization of three integrin families in the polarized Madin-Darby canine kidney (MDCK) epithelial cell line and in transformed MDCK cells lacking apical polarity. We find that MDCK cells express several beta(1) integrins, including alpha(2) beta(1), alpha(3) beta(1), and an unidentified integrin designated alpha(x) beta(1). The beta(1) integrins are the major receptors for collagens I and IV and laminin in MDCK cells, since a blocking anti-beta(1) antibody almost totally abolishes adhesion to these proteins. They also express a vitronectin receptor tentatively identified as alpha(v) beta(3), and the epithelial-specific integrin alpha(6) beta(4). The latter is not a laminin receptor in MDCK cells because a function blocking anti-alpha(6) antibody has no effect on cell adhesion to laminin. All three integrin families are expressed exclusively on both the basal and lateral surfaces, as determined by immunofluorescence microscopy and surface biotinylation. Transformed MDCK cells express beta(1) integrins as well as alpha(v) beta(3) and alpha(6) beta(4), but show alterations in the beta(1) family. Expression of alpha(x) is lacking, and the relative amount of the beta(1) subunit is diminished, resulting in the accumulation of Endo-H-sensitive alpha(3). In addition, surface biotinylation and immunofluorescence indicate that significant amounts of both alpha(2) beta(1) and alpha(3) beta(1) appear on not only the basolateral but also the apical plasma membrane. These results indicate that integrins are the major receptors for the extracellular matrix in MDCK cells, and that they may affect epithelial cell polarization by mediating not only cell-substratum but also cell-cell contacts. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02115. CHILDRENS HOSP,GI CELL BIOL RES LAB,BOSTON,MA. UNIV BASEL,BIOCTR,MAURICE E MULLER INST,CH-4056 BASEL,SWITZERLAND. NR 86 TC 93 Z9 95 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD FEB PY 1994 VL 107 BP 527 EP 541 PN 2 PG 15 WC Cell Biology SC Cell Biology GA MY783 UT WOS:A1994MY78300017 PM 7515897 ER PT J AU LAMBERTMESSERLIAN, GM ISAACSON, K CROWLEY, WF SLUSS, P SCHNEYER, AL AF LAMBERTMESSERLIAN, GM ISAACSON, K CROWLEY, WF SLUSS, P SCHNEYER, AL TI HUMAN FOLLICULAR-FLUID CONTAINS PRO-TERMINAL AND C-TERMINAL IMMUNOREACTIVE ALPHA-INHIBIN PRECURSOR PROTEINS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RAT GRANULOSA-CELLS; MESSENGER-RNAS; HUMAN SERUM; BETA-A; SUBUNIT; OVARIAN; GONADOTROPIN; EXPRESSION; RADIOIMMUNOASSAY; IMMUNOACTIVITY AB The majority of immunoactive inhibin in human follicular fluid (hFF) is devoid of pituitary cell bioactivity and is hypothesized to contain alpha-inhibin monomeric proteins known to cross-react with an inhibin antiserum (Monash 1989). The aim of this study was to define more precisely the nature of these inhibin-immunoreactive proteins using alpha-inhibin sequence-specific antisera. First, a polyclonal antiserum was raised to precursor amino acids 21-35 (PIN-1) and was used in a RIA to measure pro-alpha-inhibin-immunoreactive proteins. Western blotting was used to confirm these findings. Secondly, the binding epitope of the Monash antiserum was defined by peptide analysis to be located within the C-terminus (precursor amino acids 326-341) of alpha-inhibin, and this assay was then used to monitor the presence of C-terminal sequences. Similar levels of pro-alpha-inhibin immunoreactivity (PIN-1 RIA; N-terminus alpha-inhibin precursor) were detected in hFF collected from women with normal menstrual cycles during the follicular phase and from multiple follicles from a woman undergoing ovarian hyperstimulation during an in vitro fertilization (IVF) protocol. Western blotting with the PIN-I antibody confirmed the presence of immunoreactive proteins of 57,000 and 29,000 mol wt in the follicular fluids of both normal cycle and IVF follicles. However, ovarian hyperstimulation elevated intrafollicular C-terminal immunoreactivity (Monash RIA) compared to that in normal cycle hFF. Furthermore, intrafollicular estradiol and progesterone were significantly correlated to C-terminal activity in follicles from IVF, but not in normal cycles. These data show that 1) both pro- and C-terminal alpha-inhibin proteins are secreted into follicular fluids from normal and IVF cycles, suggesting that alpha-inhibin precursor proteins may be physiologically relevant in the process of folliculogenesis; and 2) IVF and normal cycle follicular fluids differ in their production and processing of inhibin. C1 MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, DEPT MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT GYNECOL, BOSTON, MA 02114 USA. RP LAMBERTMESSERLIAN, GM (reprint author), MASSACHUSETTS GEN HOSP, REPROD ENDOCINE UNIT BHX5, BOSTON, MA 02114 USA. FU NICHD NIH HHS [U54-HD-29164, P30-HD-28138, T32-HD-07396] NR 32 TC 32 Z9 32 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 FEB PY 1994 VL 78 IS 2 BP 433 EP 439 DI 10.1210/jc.78.2.433 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MW717 UT WOS:A1994MW71700035 PM 7508950 ER PT J AU LIANG, TJ HASEGAWA, K MUNOZ, SJ SHAPIRO, CN YOFFE, B MCMAHON, BJ FENG, CY BEI, HC ALTER, MJ DIENSTAG, JL AF LIANG, TJ HASEGAWA, K MUNOZ, SJ SHAPIRO, CN YOFFE, B MCMAHON, BJ FENG, CY BEI, HC ALTER, MJ DIENSTAG, JL TI HEPATITIS-B VIRUS PRECORE MUTATION AND FULMINANT-HEPATITIS IN THE UNITED-STATES - A POLYMERASE CHAIN REACTION-BASED ASSAY FOR THE DETECTION OF SPECIFIC MUTATION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HEPATITIS B VIRUS; FULMINANT HEPATITIS; PRECORE MUTATION; POLYMERASE CHAIN REACTION; HEPATITIS C VIRUS ID E-ANTIGEN; LIVER-DISEASE; INFECTION; MUTANT; ASSOCIATION; ANTIBODY; REGION; DNA; RNA AB Hepatitis B virus (HBV) variants with precore mutation(s) resulting in the absence of HBeAg production have been associated with the occurrence of fulminant hepatitis in Japan, Israel, and southern Europe, where the prevalence of this HBV strain appears common. In areas such as United States, where HBV infection is not endemic, the role of this mutant virus in fulminant hepatitis is unknown. We developed an amplification refractory mutation detection system to detect specifically the presence of the G to A mutation at nucleotide position 1898, which is the most frequently observed mutation resulting in a precore stop codon. In addition, this method provided a quantitative measurement of the relative ratio of one strain to the other. Using this system, we tested E-IBV strains for the presence of the stop codon mutation in sera from 40 cases of fulminant hepatitis B occurring in the United States. Serum HBV DNAs from 28 patients were analyzed successfully. A mixture of wild-type and mutant strains in various ratios were observed in 15 patients, mild type exclusively in 11, and mutant exclusively in 2. Four of these patients had undergone liver transplantation for HBV-associated cirrhosis and developed fulminant HBV-associated hepatitis after transplantation. Pre- and posttransplant serum samples from one patient were analyzed: a mixture of wild-type and mutant HBV strains was detected in both samples. Our study demonstrated that both wild-type and mutant HBV strains are associated with fulminant hepatitis, and that in some patients in the United States, factors other than precore mutations contribute to the development of fulminant hepatitis. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. JEFFERSON MED COLL,DEPT MED,DIV GASTROENTEROL & HEPATOL,PHILADELPHIA,PA 19107. CTR DIS CONTROL & PREVENT,HEPATITIS BRANCH,ATLANTA,GA 30333. VET AFFAIRS MED CTR,DIV GI,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON,TX 77030. CTR DIS CONTROL & PREVENT,ANCHORAGE,AK 99510. ALASKA NATIVE MED CTR,ANCHORAGE,AK 99510. RP LIANG, TJ (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,GASTROINTESTINAL UNIT,JACKSON 812,FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-54524]; NIDDK NIH HHS [DK-01952] NR 28 TC 73 Z9 78 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 FEB PY 1994 VL 93 IS 2 BP 550 EP 555 DI 10.1172/JCI117006 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA MY296 UT WOS:A1994MY29600017 PM 8113393 ER PT J AU RITZ, J AF RITZ, J TI TUMOR-IMMUNITY - WILL NEW KEYS UNLOCK THE DOOR SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; HOST DISEASE; GRAFT; LEUKEMIA RP RITZ, J (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 NR 13 TC 8 Z9 8 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 FEB PY 1994 VL 12 IS 2 BP 237 EP 238 PG 2 WC Oncology SC Oncology GA MW706 UT WOS:A1994MW70600002 PM 8113831 ER PT J AU LYNCH, TJ KALISH, L STRAUSS, G ELIAS, A SKARIN, A SHULMAN, LN POSNER, M FREI, E AF LYNCH, TJ KALISH, L STRAUSS, G ELIAS, A SKARIN, A SHULMAN, LN POSNER, M FREI, E TI PHASE-II STUDY OF TOPOTECAN IN METASTATIC NON-SMALL-CELL LUNG-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DNA TOPOISOMERASE-I; RANDOMIZED TRIAL; CISPLATIN; CHEMOTHERAPY; INHIBITOR; CAMPTOTHECIN; ETOPOSIDE C1 DANA FARBER CANC INST,DIV CLIN ONCOL,BOSTON,MA. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA. FU NCI NIH HHS [CA-06516, CA-19589] NR 29 TC 101 Z9 101 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 FEB PY 1994 VL 12 IS 2 BP 347 EP 352 PG 6 WC Oncology SC Oncology GA MW706 UT WOS:A1994MW70600018 PM 8113842 ER PT J AU PHILLIPS, KA NIERENBERG, AA AF PHILLIPS, KA NIERENBERG, AA TI THE ASSESSMENT AND TREATMENT OF REFRACTORY DEPRESSION SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 146th Annual Meeting of the American-Psychiatric-Association CY MAY 22-27, 1993 CL SAN FRANCISCO, CA SP Amer Psychiat Assoc ID BORDERLINE PERSONALITY-DISORDER; TREATMENT-RESISTANT DEPRESSION; BODY-DYSMORPHIC DISORDER; TRICYCLIC ANTIDEPRESSANTS; RECURRENT DEPRESSION; NON-RESPONDERS; COMBINED MAOI; FLUOXETINE; AUGMENTATION; LITHIUM AB Although treatment-refractory patients are well known to clinicians, refractory depression has received little empirical attention. Nonetheless, useful assessment and treatment strategies are available. First, it is important to determine whether a patient is truly treatment-refractory or simply has received inadequate treatment. Failure to provide adequate doses of medication for adequate periods of time is perhaps the most common cause of apparent treatment resistance. Other factors that may contribute to apparent treatment resistance are undiagnosed medical conditions, unrecognized depression subtypes, and unrecognized comorbid Axis I and II disorders. It is particularly important to detect the presence of ''secret'' comorbid disorders, which often go undiagnosed and contribute to refractory depression. Once the clinician has determined that a patient is truly treatment-refractory, many treatment approaches can be tried, including augmentation with lithium and perhaps other agents, combining antidepressants, and switching antidepressants. A modified treatment approach should be used for psychotic depression and perhaps for other depression subtypes as well (such as bipolar depression and atypical depression). Similarly, the depression associated with borderline personality disorder may best respond to a modified treatment approach. Finally, it is important to consider combining somatic treatments with psychosocial treatments in treating refractory patients. C1 MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,BOSTON,MA 02114. RP PHILLIPS, KA (reprint author), HARVARD UNIV,MCLEAN HOSP,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BELMONT,MA 02178, USA. NR 71 TC 40 Z9 40 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD FEB PY 1994 VL 55 SU S BP 20 EP 26 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA NB720 UT WOS:A1994NB72000006 PM 8077165 ER PT J AU TEOH, SK MELLO, NK MENDELSON, JH KUEHNLE, J GASTFRIEND, DR RHOADES, E SHOLAR, W AF TEOH, SK MELLO, NK MENDELSON, JH KUEHNLE, J GASTFRIEND, DR RHOADES, E SHOLAR, W TI BUPRENORPHINE EFFECTS ON MORPHINE-INDUCED AND COCAINE-INDUCED SUBJECTIVE RESPONSES BY DRUG-DEPENDENT MEN SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID RHESUS-MONKEYS; INTRAVENOUS COCAINE; HEROIN-ADDICTS; RELATIVE ABUSE; HUMANS; DETOXIFICATION; ANTAGONISTS; METHADONE; DIAZEPAM; OXAZEPAM AB The effects of daily buprenorphine treatment (4 or 8 mg/day, sublingual) on reports of subjective effects after single intravenous doses of morphine (10 mg), cocaine (30 mg), and saline placebo were studied on an inpatient clinical research ward in 26 men concurrently dependent on opioids and cocaine (DSM-III-R). Latency to detection and certainty of a drug effect, as well as drug quality (intensity, euphoria, and dysphoria), were studied before and after 10 to 12 days of buprenorphine maintenance. Saline was accurately identified by all 26 patients during the drugfree baseline and by 25 patients during buprenorphine maintenance conditions. All patients accurately identified morphine during the drugfree period before treatment with buprenorphine, but 18 (69%) of 26 patients were unable to detect morphine during buprenorphine maintenance and 2 misidentified morphine as cocaine. Six men (23%) accurately identified morphine and reported that the intensity and quality of morphine's effects were equivalent to drugfree conditions. Cocaine levels in plasma 5 minutes after intravenous cocaine injection were equivalent before and during buprenorphine treatment and averaged 282.8 +/- 43.6 and 295.2 +/- 28.8 ng/ml during 4 and 8 mg/day of buprenorphine maintenance, respectively. All patients accurately identified cocaine before and during buprenorphine maintenance, and there were no significant changes in latency to detection and certainty of a drug effect or reports of cocaine-induced intensity or euphoria during buprenorphine treatment. The concordance between responses to morphine and cocaine during inpatient buprenorphine maintenance and drug use during the first 4 weeks of outpatient buprenorphine treatment was also examined in 16 men. The effects of buprenorphine on individual responses to an acute intravenous dose of morphine or cocaine during the inpatient study did not reliably predict the frequency of heroin or cocaine self-administration during the first 4 weeks of daily outpatient buprenorphine maintenance. C1 HARVARD UNIV,MCLEAN HOSP,SCH MED,ALCOHOL & DRUG ABUSE RES CTR,BELMONT,MA 02178. MASSACHUSETTS GEN HOSP,ADDICT SERV,BOSTON,MA 02114. FU NIDA NIH HHS [DA 00101, DA 06116, DA 00064] NR 58 TC 29 Z9 29 U1 4 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD FEB PY 1994 VL 14 IS 1 BP 15 EP 27 PG 13 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA MU140 UT WOS:A1994MU14000003 PM 8151000 ER PT J AU WONG, TY MIHM, MC AF WONG, TY MIHM, MC TI ACANTHOLYTIC DERMATOSIS LOCALIZED TO GENITALIA AND CRURAL AREAS OF MALE-PATIENTS - A REPORT OF 3 CASES SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID VULVA AB A series of 3 cases of acantholytic dermatosis localized to the male genitalia and perineal area with distinct clinical and histological features is presented. These patients did not have a family history of similar disorders and had no evidence of rash elsewhere. Clinically, the eruption was characterized by multiple discrete papules or macerated patches involving the genitalia and the perineum. Histologically, the acantholytic dermatosis had features that resembled both Hailey-Hailey disease and Darier's disease. Similar clinical and histological findings have been reported in females. To the best of our knowledge, this is the first report of these lesions described confined to the genital and perineal areas in male patients. We agree with other authors that this condition may represent a distinct acantholytic eruption in the perineal area that should be distinguished from other generalized blistering acantholytic dyskeratotic disorders that may also involve the genitalia. RP WONG, TY (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV DERMATOPATHOL,WARREN BLDG,SUITE 827,FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 22 Z9 25 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD FEB PY 1994 VL 21 IS 1 BP 27 EP 32 DI 10.1111/j.1600-0560.1994.tb00687.x PG 6 WC Dermatology; Pathology SC Dermatology; Pathology GA NA687 UT WOS:A1994NA68700005 PM 8188931 ER PT J AU DRETLER, SP AF DRETLER, SP TI SPECIAL ARTICLE - CALCULUS BREAKABILITY FRAGILITY AND DURABILITY SO JOURNAL OF ENDOUROLOGY LA English DT Article AB Prior to the use of lithotripsy techniques, there was no requirement for a vocabulary to describe the relative breakability of a urinary calculus. With the introduction of lithotripsy, we became aware that calculi of different radiologic appearances or chemical compositions varied in their susceptibility to fragmentation. Because all truly new distinctions require new expressions to characterize them, we had to create a term to express this new distinction, and the term we chose was ''stone fragility.'' Currently, if we see a 1-cm calcium oxalate dihydrate stone, we say it appears fragile (''easily broken,'' from the Latin frangere, ''to break'', but if we see a dense brushite or a cystine stone, we can describe it only in terms of fragile; i.e., ''not fragile'' or, incorrectly, ''hard'': an antonym for ''fragile'' does not exist. In the interest of common understanding and more accurate quantitation of stone breakability, a neologism is suggested that has an appropriate Latin root, is easily spoken, sounds authentic, and is useful. It is proposed that, in the interest of accuracy and as a reflection of our greater sophistication regarding stone breakability, we use the Latin root dur (hard, difficult) and a suffix ile (of, like, pertaining to) to create the terms ''durile'' (adj; pertaining to or capable of being difficult to break) and ''durility'' (noun; a quality of being difficult to break or fragment). C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP DRETLER, SP (reprint author), MASSACHUSETTS GEN HOSP,CTR KIDNEY STONE,32 FRUIT ST,BOSTON,MA 02774, USA. NR 8 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD FEB PY 1994 VL 8 IS 1 BP 1 EP 3 DI 10.1089/end.1994.8.1 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA NA304 UT WOS:A1994NA30400001 PM 8186775 ER PT J AU ALPUCHEARANDA, CM RACOOSIN, EL SWANSON, JA MILLER, SI AF ALPUCHEARANDA, CM RACOOSIN, EL SWANSON, JA MILLER, SI TI SALMONELLA STIMULATE MACROPHAGE MACROPINOCYTOSIS AND PERSIST WITHIN SPACIOUS PHAGOSOMES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID EPITHELIAL-CELLS; TYPHIMURIUM; PINOCYTOSIS; VIRULENCE AB Light microscopic studies of phagocytosis showed that Salmonella typhimurium entered mouse macrophages enclosed in spacious phagosomes (SP). Viewed by time-lapse video microscopy, bone marrow-derived macrophages exposed to S. typhimurium displayed generalized plasma membrane ruffling and macropinocytosis. Phagosomes containing Salmonella were morphologically indistinguishable from macropinosomes. SP formation was observed after several methods of bacterial opsonization, although bacteria opsonized with specific IgG appeared initially in small phagosomes that later enlarged. In contrast to macropinosomes induced by growth factors, which shrink completely within 15 min, SP persisted in the cytoplasm, enlarging often by fusion with macropinosomes or other SP. A Salmonella strain containing a constitutive mutation in the phoP virulence regulatory locus (PhoP(c)) induced significantly fewer SP. Similar to Yersinia enterocolitica, PhoP(c) bacteria entered macrophages in close-fitting phagosomes, consistent with that expected for conventional receptor-mediated phagocytosis. These results suggest that formation of SP contributes to Salmonella survival and virulence. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. RI Swanson, Joel/P-4362-2014 OI Swanson, Joel/0000-0003-0900-8212 FU NIAID NIH HHS [AI-30479, AI-00917] NR 25 TC 229 Z9 229 U1 0 U2 9 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 FEB 1 PY 1994 VL 179 IS 2 BP 601 EP 608 DI 10.1084/jem.179.2.601 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MU129 UT WOS:A1994MU12900024 PM 8294870 ER PT J AU DEFOUGEROLLES, AR QIN, X SPRINGER, TA AF DEFOUGEROLLES, AR QIN, X SPRINGER, TA TI CHARACTERIZATION OF THE FUNCTION OF INTERCELLULAR-ADHESION MOLECULE (ICAM)-3 AND COMPARISON WITH ICAM-1 AND ICAM-2 IN IMMUNE-RESPONSES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; CELL-SURFACE ANTIGENS; COUNTER-RECEPTOR; COSTIMULATORY SIGNAL; LEUKOCYTE INTEGRINS; LYMPHOCYTES-T; BETA-SUBUNIT; LFA-1; LIGAND; CLONING AB We have characterized the immunobiology of the interaction of intercellular adhesion molecule 3 (ICAM-3; CD50) with its counter-receptor, leukocyte function-associated antigen 1 (LFA-1; CD11a/CD18). Purified ICAM-3 supported L;FA-l-dependent adhesion in a temperature- and cation-dependent manner. Activation of cells bearing LFA-1 increased adhesiveness for ICAM-3 in parallel to adhesiveness for ICAM-1. Although CBR-IC3/1 monoclonal antibody (mAb) blocked adhesion of cells to purified LFA-1, when tested alone, neither CBR-IC3/1 nor five novel ICAM-3 mAbs characterized here blocked adhesion of cells to purified ICAM-3 or homotypic adhesion. Two ICAM-3 mAbs, CBR-IC3/1 and CBR-IC3/2, were required to block LFA-1-dependent adhesion to purified ICAM-3- or LFA-l-dependent, ICAM-1-, ICAM-2-independent homotypic adhesion of lymphoid cell lines. Two ICAM-3 mAbs, CBR-IC3/1 and CBR-IC3/6, induced LFA-1-independent aggregation that was temperature and divalent cation dependent and was completely inhibited by ICAM-3 mAb, CBR-IC3/2, recognizing a distinct epitope. Purified ICAM-3 provided a costimulatory signal for proliferation of resting T lymphocytes. mAb to ICAM-3, together with mAbs to ICAM-1 and ICAM-2, inhibited peripheral blood lymphocyte proliferation in response to phytohemagglutinin, allogeneic stimulator cells, and specific antigen. Inhibition was almost complete and to the same level as with mAb to LFA-1, suggesting the most functionally important, and possibly all, of the ligands for LFA-1 have been defined. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA-31798] NR 58 TC 149 Z9 151 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 1 PY 1994 VL 179 IS 2 BP 619 EP 629 DI 10.1084/jem.179.2.619 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MU129 UT WOS:A1994MU12900026 PM 7905020 ER PT J AU RAVICHANDRAN, KS BURAKOFF, SJ AF RAVICHANDRAN, KS BURAKOFF, SJ TI EVIDENCE FOR DIFFERENTIAL INTRACELLULAR SIGNALING VIA CD4 AND CD8 MOLECULES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID T-CELL HYBRIDOMA; ANTIGEN RECEPTOR; ACTIVATION; EXPRESSION; MICE; TRANSDUCTION; ASSOCIATION; SELECTION; COMPLEX AB Although both the CD4 and CD8 molecules enhance antigen responsiveness mediated by the T cell receptor (TCR), it is not known whether CD4 and CD8 initiate similar or different intracellular signals when they act as coreceptors. To characterize the early signals transmitted by CD4 and CD8, both CD4 and CD8 alpha were expressed in the same murine T cell hybridoma. In the double positive transfectants, CD4 and CD8 associated with equal amounts of p56(lck) (Lck), and both molecules enhanced interleukin 2 (IL-2) production equivalently when crosslinked with suboptimal levels of anti-TCR antibody. However, in an in vitro kinase assay, crosslinking CD4 initiated fourfold greater kinase activity compared with CD8 cross-linking. In the same assay, when CD4 or CD8 was cross-linked to the TCR, novel phosphorylated proteins were found associated with the TCR/CD4 complex but not with the TCR/CD8 complex. Consistent with this data, antiphosphotyrosine immunoblotting revealed greater tyrosine phosphorylation of intracellular substrates after TCR/CD4 cross-linking compared with TCR/CD8 cross-linking. Additionally, a specific protein kinase C inhibitor (RO318220) inhibited CD8-mediated enhancement of IL-2 production far more effectively than CD4-mediated enhancement. Thus, it appears that CD8 alpha may depend more on a protein kinase C-mediated signaling pathway, whereas CD4 may rely on greater tyrosine kinase activation. Such differential signaling via CD4 and CD8 has implications for thymic ontogeny and T cell activation. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP RAVICHANDRAN, KS (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,DANA 1722,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-17528] NR 26 TC 57 Z9 57 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 FEB 1 PY 1994 VL 179 IS 2 BP 727 EP 732 DI 10.1084/jem.179.2.727 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA MU129 UT WOS:A1994MU12900038 PM 8294879 ER PT J AU MORT, EA GUADAGNOLI, E SCHROEDER, SA GREENFIELD, S MULLEY, AG MCNEIL, BJ CLEARY, PD AF MORT, EA GUADAGNOLI, E SCHROEDER, SA GREENFIELD, S MULLEY, AG MCNEIL, BJ CLEARY, PD TI THE INFLUENCE OF AGE ON CLINICAL AND PATIENT-REPORTED OUTCOMES AFTER CHOLECYSTECTOMY SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE CHOLECYSTECTOMY; AGE FACTORS; OUTCOMES; FUNCTIONAL STATUS; QUALITY OF LIFE AB Objective: To examine the relationship between the age of cholecystectomy patients and surgical complications, length of stay, symptom relief, and postdischarge functional status. Design: Patients' medical records were reviewed and patients were sent a questionnaire three months after hospital discharge. Setting: Four university-affiliated teaching hospitals. Patients: 372 patients who had a primary operation of total cholecystectomy. Outcome measures: In-hospital complications, length of stay, patient satisfaction, symptom relief, and functional status after discharge. Results: Patients over the age of GO years experienced a higher major postoperative complication rate than did younger patients (p<0.01), although the overall major complication rate was too low to determine whether factors other than age were important predictors. There was no age-related difference in minor postoperative complication rates. The older patients had a longer mean length of stay, even after statistical adjustment for covariates (p<0.05). The older patients reported similar levels of patient satisfaction, but reported recurrence of preoperative abdominal pain less often than did the younger patients (OR = 0.4, 95% CI = 0.2, 0.7). There was no statistically significant difference between the older and younger patients in postoperative functioning, except for work performance. The younger patients reported improvement in postoperative work performance, while the older patients reported a decline (p<0.01). Conclusions: Older cholecystectomy patients may experience more postoperative complications but report less recurrence of preoperative abdominal pain than do younger patients. The decline in work performance in older patients may indicate the need for a longer recuperation period. RP MORT, EA (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,50 STANIFORD ST,9TH FLOOR,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG08331-01] NR 0 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD FEB PY 1994 VL 9 IS 2 BP 61 EP 65 DI 10.1007/BF02600200 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA MW508 UT WOS:A1994MW50800001 PM 8164078 ER PT J AU YEWDELL, J LAPHAM, C BACIK, I SPIES, T BENNINK, J AF YEWDELL, J LAPHAM, C BACIK, I SPIES, T BENNINK, J TI MHC-ENCODED PROTEASOME SUBUNIT-LMP2 AND SUBUNIT-LMP7 ARE NOT REQUIRED FOR EFFICIENT ANTIGEN PRESENTATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TOXIC LYMPHOCYTES-T; CLASS-I MOLECULES; PUTATIVE PEPTIDE TRANSPORTER; INFLUENZA HEMAGGLUTININ; SIGNAL SEQUENCE; MUTANT-CELLS; RMA-S; EXPRESSION; PROTEINS AB LMP2 and LMP7 are proteins encoded by MHC genes that are tightly linked to the genes encoding TAP, the transporter that conveys peptides from the cytosol to the endoplasmic reticulum for assembly with MHC class I molecules. LMP2 and LMP7 are subunits of a subset of proteasomes, large molecular assemblies with multi-proteolytic activities believed to degrade damaged and unwanted cellular proteins. Like TAP and class I molecules themselves, expression of LMP genes is enhanced after exposure of cells to IFN-gamma. These findings implicate LMP2 and LMP7 in the cytosolic production of antigenic peptides. Doubts have been cast, however, on the role of LMP2 and LMP7 in Ag processing, because cells lacking these proteins possess class I molecules that contain peptides quantitatively and qualitatively indistinguishable from the peptides bound to class I molecules derived from normal cells. In this paper we show that cells lacking LMP2 and LMP7 present seven TAP-dependent determinants derived from viral proteins. For two determinants, the kinetics of presentation are shown to be similar for LMP-expressing and -nonexpressing cells. We also demonstrate biochemically that peptide is not limiting in the assembly of class I molecules in LMP-nonexpressing cells. These findings provide additional evidence that LMP2 and LMP7 are not required for efficient Ag presentation, and suggest that these proteins have either a more specialized role in the production of class I-associated peptides, or are not involved in the processing of proteins for-association with class I molecules. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP YEWDELL, J (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NIAID NIH HHS [AI 30581] NR 53 TC 81 Z9 82 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1994 VL 152 IS 3 BP 1163 EP 1170 PG 8 WC Immunology SC Immunology GA MV630 UT WOS:A1994MV63000023 PM 8301122 ER PT J AU BAZIL, V STROMINGER, JL AF BAZIL, V STROMINGER, JL TI METALLOPROTEASE AND SERINE-PROTEASE ARE INVOLVED IN CLEAVAGE OF CD43, CD44, AND CD16 FROM STIMULATED HUMAN GRANULOCYTES - INDUCTION OF CLEAVAGE OF L-SELECTIN VIA CD16 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN NEUTROPHILS RELEASE; HUMAN-LEUKOCYTE ANTIGENS; NODE HOMING RECEPTOR; GROWTH FACTOR-ALPHA; MONOCLONAL-ANTIBODIES; CELL ACTIVATION; SURFACE EXPRESSION; ADHESION PROTEINS; PHORBOL ESTER; MOLECULE AB CD43, CD44, CD16, and L-selectin have been previously shown to be enzymatically cleaved from stimulated leukocytes. However, little is known about the enzymes involved in these processes. Here, metalloprotease(s) inhibitable by 1,10-phenanthroline together with serine protease(s) inhibitable by Nalpha-p-tosyl-L-lysine chloromethyl ketone and 3,4-dichloroisocoumarin are shown to be involved in the cleavage of CD43, CD44, and CD16 but not in the cleavage of L-selectin on granulocytes. in addition, mAbs that recognize these individual receptors and induce their specific cleavage did not initiate cleavage of the others. In one case only, L-selectin, cleavage was also triggered by mAbs interacting with CD16 (the low affinity FcgammaR). Thus, this mechanism represents a novel pathway of L-selectin cleavage induction. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOCHEM & MOLEC BIOL,BOSTON,MA 02115. CZECHOSLOVAK ACAD SCI,INST MOLEC GENET,PRAGUE 4,CZECH REPUBLIC. FU NCI NIH HHS [CA-47554] NR 47 TC 118 Z9 118 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 1 PY 1994 VL 152 IS 3 BP 1314 EP 1322 PG 9 WC Immunology SC Immunology GA MV630 UT WOS:A1994MV63000040 PM 7507963 ER PT J AU MARGOLIN, K ARONSON, FR SZNOL, M ATKINS, MB GUCALP, R FISHER, RI SUNDERLAND, M DOROSHOW, JH ERNEST, ML MIER, JW DUTCHER, JP GAYNOR, ER WEISS, GR AF MARGOLIN, K ARONSON, FR SZNOL, M ATKINS, MB GUCALP, R FISHER, RI SUNDERLAND, M DOROSHOW, JH ERNEST, ML MIER, JW DUTCHER, JP GAYNOR, ER WEISS, GR TI PHASE-II STUDIES OF RECOMBINANT HUMAN INTERLEUKIN-4 IN ADVANCED RENAL-CANCER AND MALIGNANT-MELANOMA SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE INTERLEUKIN-4; RENAL CANCER; MALIGNANT MELANOMA; CYTOKINES; IMMUNOTHERAPY ID TUMOR-NECROSIS-FACTOR; GAMMA-INTERFERON; CELL-GROWTH; LYMPHOCYTES; ALPHA; IL-4; PROLIFERATION; EXPRESSION; MONOCYTES; INVITRO AB Interleukin (IL)-4 is a pluripotent cytokine that stimulates proliferation of activated T-cells and has antineoplastic activity against human renal tumors in animal systems. In phase I trials, IL-4 could be tolerated at doses up to 20 mu g/kg, with dose-limiting toxicities consisting of fever, fluid retention, nasal congestion, and mucositis. We report the results of two separate Phase II trials of IL-4 in 30 patients with metastatic malignant melanoma and 19 patients with advanced renal cancer. IL-4 was administered intravenously every 8 h for 14 doses in two 5-day courses separated by a 9-day interval. The first 27 patients were treated at a dose of 800 mu g/m(2), but after three of these patients developed cardiac toxicities, the dose was decreased to 600 mu g/m(2). One complete response occurred in a patient with metastatic melanoma (duration greater than or equal to 30 months). No responses were seen among the patients with renal cancer. The most frequent side effects were fever, nausea, malaise, nasal congestion, and diarrhea. Reversible hepatic and renal dysfunction were also common. Hypotension was infrequent, but transient weight gain due to fluid retention was common. The major life-threatening toxicities were cardiac and gastrointestinal. Suspected cardiac ischemia was observed in two patients, pericarditis in one, and arrhythmias in two. Three patients had major upper gastrointestinal bleeding without evidence of local tumor. We conclude that IL-4, when given as a single agent on this schedule at maximum tolerated dose, does not possess meaningful activity in renal cancer or melanoma. C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NCI,CANC THERAPY PROGRAM,BETHESDA,MD. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,BRONX,NY 10467. LOYOLA UNIV,STRITCH SCH MED,CHICAGO,IL. UNIV TEXAS,AUDIE MURPHY VET ADM HOSP,HLTH SCI CTR,SAN ANTONIO,TX. RP MARGOLIN, K (reprint author), CITY HOPE NATL MED CTR,DEPT MED ONCOL,1500 E DUARTE RD,DUARTE,CA 91010, USA. NR 22 TC 52 Z9 52 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD FEB PY 1994 VL 15 IS 2 BP 147 EP 153 DI 10.1097/00002371-199402000-00009 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA MT386 UT WOS:A1994MT38600009 PM 8136948 ER PT J AU KOLLIAS, N AF KOLLIAS, N TI MELANIN AND NON-MELANIN PHOTOPROTECTION SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,HARVARD MED SCH,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 FEB PY 1994 VL 102 IS 2 BP 267 EP 267 PG 1 WC Dermatology SC Dermatology GA MW285 UT WOS:A1994MW28500042 ER PT J AU KOLLIAS, N AF KOLLIAS, N TI THE SPECTROSCOPY OF HUMAN MELANIN PIGMENTATION SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,HARVARD MED SCH,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 1 U2 4 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 FEB PY 1994 VL 102 IS 2 BP 268 EP 268 PG 1 WC Dermatology SC Dermatology GA MW285 UT WOS:A1994MW28500053 ER PT J AU WYRICK, SD MYERS, AM BOOTH, RG KULA, NS BALDESSARINI, RJ MAILMAN, RB AF WYRICK, SD MYERS, AM BOOTH, RG KULA, NS BALDESSARINI, RJ MAILMAN, RB TI SYNTHESIS OF [N-(CH3)-H-3]-TRANS-(1R,3S)-(-)-1-PHENYL-3-N,N-DIMETHYLAMINO-1,2,3,4-TET RAHYDRONAPHTHALENE (H-2-PAT) SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE 1-PHENYL-3-AMINOTETRALINS; TRITIUM; SIGMA-LIKE RECEPTOR; TYROSINE HYDROXYLASE; DOPAMINE; H-2-PAT ID GUINEA-PIG BRAIN; SIGMA LIGANDS; BINDING; RECEPTOR; RAT AB Subsequent to the discovery that the (+)-benzomorphan sigma receptor ligands, (+)-pentazocine and (+)-N-allylnormetazocine, stimulated tyrosine hydroxylase activity and dopamine synthesis in rat striatum in vitro, we reported a similar effect on a structurally similar series of 1-phenyl-3-aminoeetrahydronaphthalenes (phenylaminotetralins, PAT's). Both racemic 1-phenyl-3-dimethylamino-6-chloro-7-hydroxytetralin (Cl,OH-PAT) and racemic 1-phenyl-3-dimethylaminotetralin (H-2-PAT) stimulated tyrosine hydroxylase with an EC(50) of approximately 0.1 mu M. The former was also found to have a non-specific dopamine releasing effect while the latter was devoid of such activity affording it the less complicated pharmacological profile of the two analogs. We previously reported the synthesis of tritium labeled CI,OH-PAT to be used in radioreceptor and autoradiography studies and found that it labeled a sigma-like site in guinea pig brain with an apparent Kd of similar to 50 pM and with a pharmacological profile unique from other known CNS receptors. Here we report the synthesis of high specific activity tritium labeled trans-(1R,3S)-(-)H-2-PAT as this enantiomer was found to be more active in the tyrosine hydroxylase assay and possessed approximately 45 fold greater affinity for the novel neuromodulatory sigma-like receptor. C1 UNIV N CAROLINA,BRAIN & DEV RES CTR,CHAPEL HILL,NC 27599. HARVARD UNIV,SCH MED,BELMONT,MA 02178. MASSACHUSETTES GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA 02178. RP WYRICK, SD (reprint author), UNIV N CAROLINA,SCH PHARM,DIV MED CHEM,RADIOSYNTH LAB,CHAPEL HILL,NC 27599, USA. NR 10 TC 9 Z9 9 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD FEB PY 1994 VL 34 IS 2 BP 131 EP 134 DI 10.1002/jlcr.2580340205 PG 4 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA MT651 UT WOS:A1994MT65100004 ER PT J AU GRANDALIANO, G VALENTE, AJ ROZEK, MM ABBOUD, HE AF GRANDALIANO, G VALENTE, AJ ROZEK, MM ABBOUD, HE TI GAMMA-INTERFERON STIMULATES MONOCYTE CHEMOTACTIC PROTEIN (MCP-1) IN HUMAN MESANGIAL CELLS SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID HUMAN ENDOTHELIAL-CELLS; ACTIVATING FACTOR MCAF; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR; MONOCLONAL-ANTIBODIES; T-CELLS; CHEMOATTRACTANT; INTERLEUKIN-8; MACROPHAGES; GLOMERULONEPHRITIS AB Cell-mediated immunity and monocyte infiltration is a prominent histologic feature of several different types of glomerulonephritis. Monocyte influx to the glomerulus correlates with glomerular hypercellularity and proteinuria. Glomerular mesangial cells, in addition to being targets for inflammatory stimuli, are also effector cells that actively participate in glomerular pathology. Mesangial cells release monocyte chemotactic protein (MCP-I). In the present article, we characterized and studied the regulation of MCP-1 released by cultured human mesangial cells. Serum-deprived mesangial cells constitutively release chemotactic activity that is neutralized by specific anti-MCP-1 antibody. An antibody to baboon MCP-I recognized 16, 15, and II kd proteins from concentrated conditioned medium that were consistent with the presence of different forms of MCP-1. Gamma interferon (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-l [II-I) markedly stimulate the release of MCP-1 as measured by a specific and sensitive radioimmunoassay. The release of MCP-1 in response to these cytokines is at least partially dependent on de novo synthesis of the protein because all three cytokines markedly stimulate the expression of MOP-I mRNA. These data demonstrate that human mesangial cells synthesize and release at least three different forms of MCP-I and that IFN-gamma and other cytokines regulate the secretion of MOP-1. IFN-gamma and MCP-I may play a major role in the recruitment and activation of monocytes to the inflamed glomerulus. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEPHROL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. RI Grandaliano, Giuseppe/G-2963-2012 FU NHLBI NIH HHS [HL 26890]; NIDDK NIH HHS [DK 33665] NR 35 TC 62 Z9 62 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD FEB PY 1994 VL 123 IS 2 BP 282 EP 289 PG 8 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA MZ689 UT WOS:A1994MZ68900021 PM 8301205 ER PT J AU LIANG, TJ BODENHEIMER, HC YANKEE, R BROWN, NV CHANG, K HUANG, JK WANDS, JR AF LIANG, TJ BODENHEIMER, HC YANKEE, R BROWN, NV CHANG, K HUANG, JK WANDS, JR TI PRESENCE OF HEPATITIS-B AND C-VIRAL GENOMES IN US BLOOD-DONORS AS DETECTED BY POLYMERASE CHAIN-REACTION AMPLIFICATION SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE POSTTRANSFUSION HEPATITIS; SURROGATE MARKERS; ANTI-HBC; ALT ELEVATION ID TRANSFUSION-TRANSMITTED VIRUSES; SERUM ALANINE AMINOTRANSFERASE; CHRONIC LIVER-DISEASE; NON-A-HEPATITIS; CORE ANTIGEN; NUCLEOTIDE-SEQUENCES; ISOLATED ANTIBODY; SURFACE-ANTIGEN; INFECTION; DNA AB Hepatitis C virus (HCV) represents a major cause of posttransfusion hepatitis worldwide. Posttransfusion hepatitis associated with hepatitis B virus (HBV) continues to occur. HBsAg-negative donor sera from the Rhode Island Blood Center between 1987 and 1988 were screened using more sensitive techniques to assess the prevalence of low level HBV infection. Group I consists of 866 healthy blood donors without HBV serelogic markers, group II consists of 377 donors with ALT elevations (> 45 IU/L), group II consists of 148 donors positive for anti-HBc, and group IV consists of eight donors positive for both surrogate markers. A sensitive monoclonal immunoradiometric assay (M-IRMA) was employed for detection of HBsAg-associated epitopes (detection limit of 20 pg/ml) in serum. A subset of sera were analyzed for the presence of HBV DNA using the method of anti-HBs capture of HBV related virions in serum followed by polymerase chain reaction (PCR) amplification. Using these techniques, 0.8% and 1.7% of donors were positive for HBsAg and HBV DNA respectively in group I. In contrast, 0.9% and 9.5% in group II and 0.7% and 18.1% in group III were positive, respectively. There were eight donors with both ALT elevation and anti-HBc; and four (50%) of these were positive for HBV DNA. In the group with anti-HBc, the majority (80%) of donors with HBV DNA had either no or low (signal to noise ratio < 10) anti-HBs titer. Using anti-HCV testing and reverse transcription-PCR for detection of HCV genomes, we detected evidence of HCV infection in nine of the 49 donors with low level HBV DNA. We demonstrate that low level HBV viremia otherwise undetectable by conventional method are prevalent in donor grups with either or both of the surrogate and HCV infection either alone or as co-infecting agent are also common in this population, (C) 1994 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MT SINAI SCH MED,NEW YORK,NY. BROWN UNIV,RHODE ISL BLOOD CTR,PROVIDENCE,RI. MASSACHUSETTS GEN HOSP,CTR CANC,MOLEC HEPATOL LAB,BOSTON,MA. RP LIANG, TJ (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,JACKSON 812,FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-54524]; NIAAA NIH HHS [AA-02666]; NIDDK NIH HHS [DK01952] NR 50 TC 40 Z9 42 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 1994 VL 42 IS 2 BP 151 EP 157 DI 10.1002/jmv.1890420210 PG 7 WC Virology SC Virology GA MT785 UT WOS:A1994MT78500009 PM 8158110 ER PT J AU ASCH, DA PATTON, JP AF ASCH, DA PATTON, JP TI CONFLICTS OVER POSTEXPOSURE TESTING FOR HUMAN-IMMUNODEFICIENCY-VIRUS - CAN NEGOTIATED SETTLEMENTS HELP SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; CONFIDENTIALITY; ETHICS; GAME THEORY; HEALTH POLICY; HUMAN IMMUNODEFICIENCY VIRUS; PRIVACY; PROFESSIONAL PATIENT RELATIONS ID PROGNOSTIC INFORMATION; INFECTION; HIV AB Health care workers with needlestick exposures to patients' blood often request a test of the patient for evidence of infection with human immunodeficiency virus. If the patient refuses the test, a conflict develops between the interests of the health care worker and those of the patient. Traditional approaches to this dilemma attempt to balance the rights or utilities of abstract patients and health care workers. While these approaches have the advantage of offering clear guidelines in advance of conflict, the interests of the actual participants may differ from those used to create the guidelines. In nonmedical settings, conflicts are often resolved efficiently through negotiation and monetary exchanges. Although negotiated monetary settlements between health care workers and patients may be an impractical way to resolve medical conflicts, models developed from these perspectives provide insights into the individual interests of physicians and patients. Changing existing rules about medical record documentation, or increasing the penalties for the misuse of medical information, may satisfy the interests on both sides of the conflict and so represent integrative bargaining solutions. Even so, as the relationship between health care workers and their patients evolves, more explicit strategies for negotiation may become a reasonable solution to the problem of conflict. C1 UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,MED SERV,PHILADELPHIA,PA 19104. RP ASCH, DA (reprint author), UNIV PENN,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104, USA. NR 14 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 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD FEB PY 1994 VL 19 IS 1 BP 41 EP 59 PG 19 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA NC715 UT WOS:A1994NC71500004 PM 8201289 ER PT J AU BARSKY, AJ CLEARY, PD SARNIE, MK RUSKIN, JN AF BARSKY, AJ CLEARY, PD SARNIE, MK RUSKIN, JN TI PANIC DISORDER, PALPITATIONS, AND THE AWARENESS OF CARDIAC ACTIVITY SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; CORONARY-ARTERY DISEASE; PRIMARY CARE; CHEST PAIN; SOMATOSENSORY AMPLIFICATION; HYPOCHONDRIACAL FEARS; PSYCHIATRIC-DISORDERS; MEDICAL OUTPATIENTS; SOCIAL MORBIDITY; ANXIETY NEUROSIS AB One hundred forty-five consecutive patients referred for ambulatory electrocardiographic monitoring for the evaluation of palpitations were studied just before monitoring. They were compared with 75 asymptomatic, nonpatient volunteers. The research battery included a structured diagnostic interview, self-report questionnaires, and perceptual tasks measuring awareness of cardiac activity. After monitoring, symptom reports were compared with concurrent electrocardiographic recordings to determine their accuracy. Forty palpitation patients (27.6%) had DSM-III-R lifetime panic disorder, and 27 (18.6%) had current (1-month) panic disorder. Panic patients were significantly more likely to describe their palpitations as ''racing'' or ''pounding'' and to have been awakened from sleep by them. They did not have more cardiac arrhythmias during 24-hour, electrocardiographic monitoring, and their symptom reports were significantly less likely to be due to demonstrable cardiac irregularities. They were not more accurately aware of resting heartbeat than nonpanic palpitation patients. They did score higher on self-report measures of somatization, hypochondriasis, and bodily amplification. C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT SOCIAL MED,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT MED,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RP BARSKY, AJ (reprint author), HARVARD UNIV,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA 02138, USA. FU NHLBI NIH HHS [HL43216] NR 69 TC 57 Z9 58 U1 8 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD FEB PY 1994 VL 182 IS 2 BP 63 EP 71 DI 10.1097/00005053-199402000-00001 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA MX085 UT WOS:A1994MX08500001 PM 8308534 ER PT J AU VANSELOW, J GRABCZYK, E PING, J BAETSCHER, M TENG, S FISHMAN, MC AF VANSELOW, J GRABCZYK, E PING, J BAETSCHER, M TENG, S FISHMAN, MC TI GAP-43 TRANSGENIC MICE - DISPERSED GENOMIC SEQUENCES CONFER A GAP-43-LIKE EXPRESSION PATTERN DURING DEVELOPMENT AND REGENERATION SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GAP-43; NEUROMODULIN; TRANSGENIC MICE; REGENERATION; DEVELOPMENT; INTRON ID GROWTH-ASSOCIATED PROTEIN; KINASE-C SUBSTRATE; GENE-EXPRESSION; MESSENGER-RNA; NERVE GROWTH; EUKARYOTIC RIBOSOMES; SYNAPTIC PLASTICITY; BINDING-PROTEIN; SPINAL-CORD; GLOBIN GENE AB Using transgenic mice, we have examined the expression pattern conferred by regions of genomic GAP-43 coupled to beta-galactosidase. We demonstrate that gene constructions that include the GAP-43 5'-flanking region along with sufficient sequences of the first intron drive beta-galactosidase (lacZ) expression to mimic in many regards the complex spatial and temporal pattern of endogenous GAP-43 expression. Transgene expression reaches peak levels during development, and persists at high levels in particular adult brain regions, such as the hippocampus and olfactory bulb. The inclusion of a stretch of the first intron in the construction is necessary to prevent expression outside of the nervous system, indicating that some of the cell specificity of GAP-43 expression is due to suppression of expression in inappropriate tissues. Injury caused by sciatic nerve crush causes reexpression of the transgene in adult sensory and motor neurons. This genomic region of GAP-43, therefore, includes elements responsive to neuronal growth signals that regulate both development and regeneration. C1 MASSACHUSETTS GEN HOSP,DEV BIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 54 TC 62 Z9 62 U1 0 U2 1 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 FEB PY 1994 VL 14 IS 2 BP 499 EP 510 PG 12 WC Neurosciences SC Neurosciences & Neurology GA MV319 UT WOS:A1994MV31900004 PM 8301350 ER PT J AU LU, XM FISCHMAN, AJ JYAWOOK, SL HENDRICKS, K TOMPKINS, RG YARMUSH, ML AF LU, XM FISCHMAN, AJ JYAWOOK, SL HENDRICKS, K TOMPKINS, RG YARMUSH, ML TI ANTISENSE DNA DELIVERY IN-VIVO - LIVER TARGETING BY RECEPTOR-MEDIATED UPTAKE SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE ANTISENSE DNA DELIVERY; RECEPTOR-MEDIATED UPTAKE; ASIALOGLYCOPROTEIN; OLIGODEOXYNUCLEOTIDES; SIALOGLYCOPROTEIN ID IDENTIFICATION; BINDING; CELLS; SUBPOPULATIONS; ANTIBODIES AB Antisense oligodeoxynucleotides coupled to asialoglycoprotein carrier molecules were evaluated in terms of their ability to accumulate preferentially in the liver and thus potentially serve as an important method to regulate liver gene expression. Methods: Native and asialo-human alpha-1 acid glycoproteins were derivatized with low molecular weight poly(l)lysine and complexed with an antisense DNA (67 mer) complementary to the 5' end of rat serum albumin mRNA. The asialoglycoprotein antisense complex (conjugate) was characterized with respect to size, stability, and anti-sense loading, and the biodistribution of the conjugate was determined for normal rats at 5 min and 1, 6, and 24 hr after intravenous injection. In vivo stability of the anti-sense asialoglycoprotein complex was also evaluated using double-labeled P-32-antisense and H-3-glycoprotein) preparations. Results: The results of the conjugate characterization studies demonstrated that at least 30% of the anti-sense DNA dissociated from the carrier after 7 min under chromatographic conditions. When the conjugate was incubated with PBS, MEM or MEM plus 10% FBS for 1 hr at 37 degrees C, about 85% of the antisense DNA was dissociated from the carrier. The results of the biodistribution studies showed that the accumulation of the asialo-glycoprotein anti-sense complex in the liver was rapid and greatly exceeded the accumulation of the sialo-glycoprotein antisense analog or antisense alone. Conclusion: These findings have significant implications for the targeted delivery of therapeutic antisense molecules to the liver. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. SHRINERS BURN INST,BOSTON,MA. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ. NR 23 TC 57 Z9 58 U1 0 U2 1 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 FEB PY 1994 VL 35 IS 2 BP 269 EP 275 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA MX196 UT WOS:A1994MX19600020 PM 8294998 ER PT J AU SHAMBERGER, RC TARBELL, NJ PEREZATAYDE, AR GRIER, HE AF SHAMBERGER, RC TARBELL, NJ PEREZATAYDE, AR GRIER, HE TI MALIGNANT SMALL ROUND-CELL TUMOR (EWINGS-PNET) OF THE CHEST-WALL IN CHILDREN SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 15-18, 1993 CL HILTON HEAD, SC SP AMER PEDIAT SURG ASSOC DE EWINGS SARCOMA, CHEST WALL; ASKINS TUMOR; PRIMITIVE NEUROECTODERMAL TUMOR ID TERM FOLLOW-UP; PERIPHERAL NEUROEPITHELIOMA; THORACOPULMONARY REGION; PROGNOSTIC-SIGNIFICANCE; MULTIMODAL THERAPY; NEURAL ORIGIN; YOUNG-ADULTS; ASKIN TUMOR; SARCOMA; BONE C1 CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT RADIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP SHAMBERGER, RC (reprint author), CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT SURG,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 39 TC 33 Z9 34 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 1994 VL 29 IS 2 BP 179 EP 185 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA MX667 UT WOS:A1994MX66700009 PM 8176588 ER PT J AU GAISSERT, HA MATHISEN, DJ GRILLO, HC VACANTI, JP WAIN, JC AF GAISSERT, HA MATHISEN, DJ GRILLO, HC VACANTI, JP WAIN, JC TI TRACHEOBRONCHIAL SLEEVE RESECTION IN CHILDREN AND ADOLESCENTS SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 15-18, 1993 CL HILTON HEAD, SC SP AMER PEDIAT SURG ASSOC DE BRONCHOPLASTIC TECHNIQUES, PEDIATRIC ID LUNG; VENTILATION; LOBECTOMY C1 MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DEPT SURG,BOSTON,MA 02115. NR 18 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 1994 VL 29 IS 2 BP 192 EP 198 DI 10.1016/0022-3468(94)90316-6 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA MX667 UT WOS:A1994MX66700011 PM 8176590 ER PT J AU VACANTI, CA PAIGE, KT KIM, WS SAKATA, J UPTON, J VACANTI, JP AF VACANTI, CA PAIGE, KT KIM, WS SAKATA, J UPTON, J VACANTI, JP TI EXPERIMENTAL TRACHEAL REPLACEMENT USING TISSUE-ENGINEERED CARTILAGE SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 15-18, 1993 CL HILTON HEAD, SC SP AMER PEDIAT SURG ASSOC DE TRACHEAL DEFECTS, REPAIR ID RECONSTRUCTION; DEFECTS C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PLAST SURG,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT SURG,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT OTOLARYNGOL,BOSTON,MA. BETH ISRAEL HOSP,DEPT PLAST SURG,BOSTON,MA 02215. NR 23 TC 106 Z9 131 U1 4 U2 14 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 1994 VL 29 IS 2 BP 201 EP 205 DI 10.1016/0022-3468(94)90318-2 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA MX667 UT WOS:A1994MX66700013 PM 8176592 ER PT J AU DONAHOE, PK GUSTAFSON, ML AF DONAHOE, PK GUSTAFSON, ML TI EARLY ONE-STAGE SURGICAL RECONSTRUCTION OF THE EXTREMELY HIGH VAGINA IN PATIENTS WITH CONGENITAL ADRENAL-HYPERPLASIA SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 15-18, 1993 CL HILTON HEAD, SC SP AMER PEDIAT SURG ASSOC DE CONGENITAL ADRENAL HYPERPLASIA ID FEMALES C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP DONAHOE, PK (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT SURG SERV,WARREN 1133,BOSTON,MA 02114, USA. NR 8 TC 31 Z9 34 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 1994 VL 29 IS 2 BP 352 EP 358 DI 10.1016/0022-3468(94)90347-6 PG 7 WC Pediatrics; Surgery SC Pediatrics; Surgery GA MX667 UT WOS:A1994MX66700042 PM 8176619 ER PT J AU SUEN, HC LOSTY, P DONAHOE, PK SCHNITZER, JJ AF SUEN, HC LOSTY, P DONAHOE, PK SCHNITZER, JJ TI COMBINED ANTENATAL THYROTROPIN-RELEASING-HORMONE AND LOW-DOSE GLUCOCORTICOID THERAPY IMPROVES THE PULMONARY BIOCHEMICAL IMMATURITY IN CONGENITAL DIAPHRAGMATIC-HERNIA SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 15-18, 1993 CL HILTON HEAD, SC SP AMER PEDIAT SURG ASSOC DE CONGENITAL DIAPHRAGMATIC HERNIA; ANTENATAL THERAPY, GLUCOCORTICOID, THYROTROPIN RELEASING HORMONE ID FETAL RABBIT LUNG; THYROID-HORMONES; ACCELERATED APPEARANCE; PREMATURE-INFANTS; SURFACTANT; HYPOPLASIA; MATURATION; PHOSPHATIDYLCHOLINE; CORTICOSTEROIDS; BETAMETHASONE C1 MASSACHUSETTS GEN HOSP,PEDIAT SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN THORAC SURG UNIT,PEDIAT SURG RES LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. NR 46 TC 41 Z9 42 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD FEB PY 1994 VL 29 IS 2 BP 359 EP 363 DI 10.1016/0022-3468(94)90348-4 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA MX667 UT WOS:A1994MX66700043 PM 8176620 ER PT J AU NONELL, S REDMOND, RW AF NONELL, S REDMOND, RW TI ON THE DETERMINATION OF QUANTUM YIELDS FOR SINGLET MOLECULAR-OXYGEN PHOTOSENSITIZATION SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Editorial Material C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RP NONELL, S (reprint author), CETS,INST QUIM SARRIA,E-08017 BARCELONA,SPAIN. RI Nonell, Santi/L-2561-2013 OI Nonell, Santi/0000-0002-8900-5291 NR 2 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD FEB PY 1994 VL 22 IS 2 BP 171 EP 172 DI 10.1016/1011-1344(93)06972-6 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MY020 UT WOS:A1994MY02000011 ER PT J AU JELLINEK, MS AF JELLINEK, MS TI THE OUTPATIENT MILIEU SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP JELLINEK, MS (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,15 PARKMAN ST ACC725,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 1994 VL 33 IS 2 BP 277 EP 279 DI 10.1097/00004583-199402000-00018 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA MT230 UT WOS:A1994MT23000018 PM 8150801 ER PT J AU BIEDERMAN, J ROSENBAUM, JR AF BIEDERMAN, J ROSENBAUM, JR TI CHILD-ADULT ANXIETY DISORDERS - REPLY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD FEB PY 1994 VL 33 IS 2 BP 280 EP 281 DI 10.1097/00004583-199402000-00020 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA MT230 UT WOS:A1994MT23000020 ER PT J AU LITVACK, F EIGLER, N MARGOLIS, J ROTHBAUM, D BRESNAHAN, JF HOLMES, D UNTEREKER, W LEON, M KENT, K PICHARD, A KING, S GHAZZAL, Z CUMMINS, F KRAUTHAMER, D PALACIOS, I BLOCK, P HARTZLER, GO ONEILL, W COWLEY, M ROUBIN, G KLEIN, LW FRANKEL, PS ADAMS, C GOLDENBERG, T LAUDENSLAGER, J GRUNDFEST, WS FORRESTER, JS AF LITVACK, F EIGLER, N MARGOLIS, J ROTHBAUM, D BRESNAHAN, JF HOLMES, D UNTEREKER, W LEON, M KENT, K PICHARD, A KING, S GHAZZAL, Z CUMMINS, F KRAUTHAMER, D PALACIOS, I BLOCK, P HARTZLER, GO ONEILL, W COWLEY, M ROUBIN, G KLEIN, LW FRANKEL, PS ADAMS, C GOLDENBERG, T LAUDENSLAGER, J GRUNDFEST, WS FORRESTER, JS TI PERCUTANEOUS EXCIMER-LASER CORONARY ANGIOPLASTY - RESULTS IN THE FIRST CONSECUTIVE 3,000 PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ANGIOGRAPHIC FOLLOW-UP; RESTENOSIS; DETERMINANTS; OCCLUSION; REGISTRY; SUCCESS; DISEASE AB Objectives. We report the comprehensive results of the first consecutive 3,000 patients treated in an excimer laser coronary angioplasty registry. Background. Excimer laser coronary angioplasty involves the use of a pulsed, 308-nm ultraviolet laser transmitted by optical fibers to reduce coronary stenoses. Preliminary reports have described safety and efficacy profiles in small numbers of patients. Methods, Patients were enrolled in a prospective, nonrandomized manner. The catheters used were 1.3, 1.6, 2.0, 2.2 and 2.4 mm in diameter, at energy densities up to 70 mJ/mm(2). Procedures were performed by standard angioplasty technique with conventional guide catheters. Results. Seventy-five percent of patients were male, 68% were in Canadian Cardiovascular Society functional class III or IV and the cohort included 3,592 lesions, Procedural success (final stenosis less than or equal to 50% without in-hospital Q wave myocardial infarction, coronary artery bypass surgery or death) was 90% and did not differ between the first 2,000 and the last 1,000 patients treated. There was no significant difference in successor complication rates with respect to lesion length, nor were there differences between selected complex and simple lesions. Complications included in-hospital bypass surgery (3.8%), Q wave myocardial infarction (2.1%) and death (0.5%). Coronary artery perforation occurred in 1.2% of patients (1% of lesions) but significantly decreased to 0.4% in the last 1,000 patients (0.3% of lesions). Angiographic dissection occurred in 13% of lesions, transient occlusion in 3.4% and sustained occlusion in 3.1%. Comprehensive lesion morphologic data collected in the latter portion of the study showed the procedure predominantly limited to American College of Cardiology-American Heart Association type B2 and C lesions, with no significant difference in short-term outcome between groups. Conclusions. Excimer laser angioplasty can be safely and effectively applied, even in a variety of complex lesions not well suited for percutaneous transluminal coronary angioplasty. These types may include aorto-ostial, long lesions, total occlusions crossable with a wire, diffuse disease and vein grafts. Most recent data show a trend for the selection of predominantly complex lesions and a reduction in the incidence of perforation. This procedure may broaden the therapeutic window for the interventional treatment of selected complex coronary artery disease. C1 CEDARS SINAI MED CTR,DEPT MED,DIV CARDIOL,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. MIAMI HEART INST,MIAMI BEACH,FL 33140. UNIV INDIANAPOLIS,ST VINCENTS HOSP,INDIANAPOLIS,IN 46227. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. PHILADELPHIA HEART INST,PHILADELPHIA,PA. WASHINGTON HOSP CTR,WASHINGTON,DC 20010. EMORY UNIV,ATLANTA,GA 30322. ST LUKES HOSP,MILWAUKEE,WI. S MIAMI HOSP,MIAMI,FL 33143. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. ST VINCENT HOSP & MED CTR,PORTLAND,OR 97225. ST LUKES HOSP,KANSAS CITY,MO. WILLIAM BEAUMONT HOSP,ROYAL OAK,MI 48072. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. UNIV ALABAMA,BIRMINGHAM,AL. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. DANIEL FREEMAN MEM HOSP,INGLEWOOD,CA 90301. ADV INTERVENT SYST,IRVINE,CA. NR 31 TC 101 Z9 101 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 FEB PY 1994 VL 23 IS 2 BP 323 EP 329 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NR752 UT WOS:A1994NR75200007 PM 8294681 ER PT J AU ABASCAL, VM MORENO, PR RODRIGUEZ, L MONTERROSO, VM PALACIOS, IF DEMPSEY, A WEYMAN, AE DAVIDOFF, R AF ABASCAL, VM MORENO, PR RODRIGUEZ, L MONTERROSO, VM PALACIOS, IF DEMPSEY, A WEYMAN, AE DAVIDOFF, R TI DOPPLER PRESSURE HALF-TIME IN MITRAL-STENOSIS - INACCURATE IN THE ELDERLY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 BOSTON UNIV,MED CTR,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A194 EP A194 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800765 ER PT J AU BADIMON, J FERNANDEZORTIZ, A MEYER, B MAILHAC, A CHESEBRO, JH MCBANE, R HASSINGER, N FALK, E FALLOHN, J FUSTER, V BADIMON, L AF BADIMON, J FERNANDEZORTIZ, A MEYER, B MAILHAC, A CHESEBRO, JH MCBANE, R HASSINGER, N FALK, E FALLOHN, J FUSTER, V BADIMON, L TI DIFFERENT RESPONSE TO BALLOON ANGIOPLASTY OF CAROTID AND CORONARY-ARTERIES - ACUTE PLATELET DEPOSITION AND INTIMAL THICKENING SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 0 TC 0 Z9 0 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 FEB PY 1994 SI SI BP A234 EP A234 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800924 ER PT J AU BALINO, NAP RODRIGUEZ, OMA ITURRIA, M MERETTA, A CRAGNOLINO, D PERRONE, S MELE, E PALACIOS, I AF BALINO, NAP RODRIGUEZ, OMA ITURRIA, M MERETTA, A CRAGNOLINO, D PERRONE, S MELE, E PALACIOS, I TI LEFT-VENTRICULAR EJECTION FRACTION RESPONSE TO AMRINONE BOLUS - A CHALLENGE IN ORDER TO IDENTIFYING PATIENTS WITH ISCHEMIC CARDIOMYOPATHY AND REVERSIBLE CHRONIC LEFT-VENTRICULAR DYSFUNCTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SANATORIO ANCHORENA,SANATORIO GUEMES,BUENOS AIRES,ARGENTINA. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A343 EP A343 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801358 ER PT J AU CASON, BA HICKEY, RF SHUBAYEV, I AF CASON, BA HICKEY, RF SHUBAYEV, I TI ATP-K CHANNEL BLOCKADE IMPROVES CORONARY AUTOREGULATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 SAN FRANCISCO VET AFFAIRS MED CTR,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A379 EP A379 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801499 ER PT J AU CHEN, CG PRADIAL, JA CHEN, MH ABBAS, SA WEYMAN, AE GILLAM, L AF CHEN, CG PRADIAL, JA CHEN, MH ABBAS, SA WEYMAN, AE GILLAM, L TI RESPONSE OF LEFT-VENTRICULAR REGIONAL WALL THICKENING TO DOBUTAMINE INFUSION IS CRITICALLY DEPENDENT ON THE BALANCE BETWEEN REGIONAL CORONARY FLOW AND OXYGEN-CONSUMPTION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 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 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 FEB PY 1994 SI SI BP A121 EP A121 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800476 ER PT J AU CHEN, MH DEPRADA, JAV PADIAL, LR GUERRERO, JL SCHWAMMENTHAL, E GILLAM, L WEYMAN, AE LEVINE, RA CHEN, CG AF CHEN, MH DEPRADA, JAV PADIAL, LR GUERRERO, JL SCHWAMMENTHAL, E GILLAM, L WEYMAN, AE LEVINE, RA CHEN, CG TI INTRACARDIAC ULTRASOUND PROVIDES MORE ACCURATE ASSESSMENT OF LEFT-VENTRICULAR VOLUME AS COMPARED WITH BIPLANE ANGIOGRAPHY - AN IN-VITRO STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 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 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 FEB PY 1994 SI SI BP A462 EP A462 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801830 ER PT J AU CHEN, MH DEPRADA, JAV GUERRERO, JL LUIS, RP WEYMAN, AE LEVINE, RA GILLAM, L CHEN, CG AF CHEN, MH DEPRADA, JAV GUERRERO, JL LUIS, RP WEYMAN, AE LEVINE, RA GILLAM, L CHEN, CG TI INTRACARDIAC ULTRASOUND MEASUREMENT OF LEFT-VENTRICULAR WALL THICKENING - IN-VIVO VALIDATION WITH SONOMICROMETERS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 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 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 FEB PY 1994 SI SI BP A462 EP A462 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801832 ER PT J AU CHEN, MH PADIAL, LR VUILLE, C GUERRERO, JL WEYMAN, AE PICARD, MH AF CHEN, MH PADIAL, LR VUILLE, C GUERRERO, JL WEYMAN, AE PICARD, MH TI EFFECT OF PULSATILE PRESSURE ON ECHOCARDIOGRAPHIC CONTRAST PERSISTENCE - IS IT DUE TO PEAK OR DURATION OF PRESSURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A25 EP A25 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800093 ER PT J AU CHESEBRO, JH FUSTER, V CALIFF, RM HARRINGTON, RA KLEIMAN, NS KEREIAKES, DJ COHEN, M CHAPEKIS, A GOLD, HK BEAR, P RAO, AK DEBOWEY, D SCHWARTZ, D HENIS, M TOPOL, EJ AF CHESEBRO, JH FUSTER, V CALIFF, RM HARRINGTON, RA KLEIMAN, NS KEREIAKES, DJ COHEN, M CHAPEKIS, A GOLD, HK BEAR, P RAO, AK DEBOWEY, D SCHWARTZ, D HENIS, M TOPOL, EJ TI RECOMBINANT HIRUDIN FOR UNSTABLE ANGINA - A PILOT MULTICENTER, RANDOMIZED ANGIOGRAPHIC TRIAL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 FEB PY 1994 SI SI BP A363 EP A363 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801436 ER PT J AU CURWIN, JH MCGOVERN, BA GARAN, H RUSKIN, JN BROOKS, R AF CURWIN, JH MCGOVERN, BA GARAN, H RUSKIN, JN BROOKS, R TI THE ROLE OF MEDICAL THERAPY IS UNCERTAIN IN PATIENTS WITH RECURRENT SYNCOPE AND POSITIVE TILT-TABLE TESTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A330 EP A330 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801303 ER PT J AU DBERMAN, M MARECKI, F GEWIRTZ, H AF DBERMAN, M MARECKI, F GEWIRTZ, H TI MYOCARDIAL ADAPTATION TO ACUTE, DEMAND INDUCED ISCHEMIA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 RHODE ISL HOSP,PROVIDENCE,RI 02902. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 1 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 FEB PY 1994 SI SI BP A373 EP A373 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801474 ER PT J AU DEPRADA, JAV CHEN, MH PADIAL, LR GUERRERO, JL JIANG, J SCHWAMMENTHAL, E WEYMAN, AE CHEN, CG LEVINE, RA AF DEPRADA, JAV CHEN, MH PADIAL, LR GUERRERO, JL JIANG, J SCHWAMMENTHAL, E WEYMAN, AE CHEN, CG LEVINE, RA TI ASSESSMENT OF RIGHT-VENTRICULAR VOLUME AND FUNCTION WITH INTRACARDIAC ULTRASONOGRAPHY - IN-VIVO VALIDATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A411 EP A411 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801628 ER PT J AU DOWNING, J LITTMAN, AB SCHEER, J AF DOWNING, J LITTMAN, AB SCHEER, J TI POOR RECOVERY IN YOUNG-WOMEN WITH CORONARY HEART-DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A400 EP A400 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801585 ER PT J AU FERNANDEZORTIZ, A AF FERNANDEZORTIZ, A TI THE LIPID-RICH CORE IS THE THROMBOGENIC COMPONENT OF HUMAN ATHEROSCLEROTIC LESIONS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. NR 0 TC 1 Z9 1 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 FEB PY 1994 SI SI BP A437 EP A437 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801730 ER PT J AU FERNANDEZORTIZ, A BADIMON, J FALK, E FUSTER, V CHESEBRO, J BADIMON, L AF FERNANDEZORTIZ, A BADIMON, J FALK, E FUSTER, V CHESEBRO, J BADIMON, L TI THROMBOGENICITY OF HUMAN ARTERIAL-WALL - IMPLICATIONS FOR VASCULAR INTERVENTIONS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 0 TC 0 Z9 0 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 FEB PY 1994 SI SI BP A184 EP A184 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800725 ER PT J AU FONTAINE, AA LEVINE, RA MENENDEZ, M WILLIAMS, K REEVES, WF PAWLUKIEWICZ, SW KASSEL, J YOGANATHAN, AP AF FONTAINE, AA LEVINE, RA MENENDEZ, M WILLIAMS, K REEVES, WF PAWLUKIEWICZ, SW KASSEL, J YOGANATHAN, AP TI MITRAL REGURGITANT JET MOMENTUM QUANTITATION THROUGH DIGITAL AUSCULTATION - AN IN-VITRO STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MCG INT,NEW HAVEN,CT. GEORGIA INST TECHNOL,ATLANTA,GA 30332. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A176 EP A176 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800693 ER PT J AU GEBARA, OCE MCKENNA, C KEOUGH, J XU, P LIPINSKA, I MITTLEMAN, M WEINRAUCH, L DELIA, J TOFLER, GH AF GEBARA, OCE MCKENNA, C KEOUGH, J XU, P LIPINSKA, I MITTLEMAN, M WEINRAUCH, L DELIA, J TOFLER, GH TI ASSOCIATION BETWEEN GLYCOSYLATED HEMOGLOBIN AND LEVELS OF FIBRINOGEN IN PATIENTS WITH TYPE-1 DIABETES-MELLITUS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,DEACONESS HOSP,SCH MED,INST PREVENT CARDIOVASC DIS,BOSTON,MA 02115. HARVARD UNIV,JOSLIN DIABET CTR,SCH MED,BOSTON,MA 02115. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A163 EP A163 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800641 ER PT J AU GRIMES, RY WALKER, PG AF GRIMES, RY WALKER, PG TI IMPACT OF ATRIAL COMPLIANCE ON PULMONARY VEIN FLOW REVERSAL IN MITRAL REGURGITATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 GEORGIA INST TECHNOL,ATLANTA,GA 30332. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A366 EP A366 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801447 ER PT J AU HEINRICH, RS WILLIAMS, KM GRIMES, RY LEVINE, RA YOGANATHAN, AP AF HEINRICH, RS WILLIAMS, KM GRIMES, RY LEVINE, RA YOGANATHAN, AP TI MITRAL INFLOW AFFECTS AORTIC REGURGITATION JET AREA - AN IN-VITRO STUDY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 GEORGIA INST TECHNOL,ATLANTA,GA 30332. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A221 EP A221 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800873 ER PT J AU HOPMEYER, J YANG, S FONTAINE, AA SCHWAMMENTHAL, E LEVINE, RA YOGANATHAN, AP AF HOPMEYER, J YANG, S FONTAINE, AA SCHWAMMENTHAL, E LEVINE, RA YOGANATHAN, AP TI QUANTIFICATION OF REGURGITATION BY THE PROXIMAL ISOVELOCITY SURFACE-AREA (PISA) TECHNIQUE - DETAILED VALIDATION BY LASER-DOPPLER ANEMOMETRY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 GEORGIA INST TECHNOL,ATLANTA,GA 30332. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A249 EP A249 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800982 ER PT J AU JACOBS, AK WEINER, BH RAIZNER, A SCHOENFELD, DA SCHEER, J MAHRER, P COTE, G SLACK, J KELLETT, MA JORGENSEN, M LEAF, A AF JACOBS, AK WEINER, BH RAIZNER, A SCHOENFELD, DA SCHEER, J MAHRER, P COTE, G SLACK, J KELLETT, MA JORGENSEN, M LEAF, A TI THE IMPACT OF FISH-OIL ON RESTENOSIS FOLLOWING CORONARY ANGIOPLASTY - THE FISH-OIL RESTENOSIS TRIAL (FORT) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A59 EP A59 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800230 ER PT J AU JIANG, L LEVINE, RA WEYMAN, AE HANDSCHUMACHER, MD AF JIANG, L LEVINE, RA WEYMAN, AE HANDSCHUMACHER, MD TI ACCURACY OF 3-DIMENSIONAL ECHOCARDIOGRAPHIC RECONSTRUCTION BY ELECTROMAGNETIC POSITIONAL LOCATION - A FURTHER STEP TOWARD PRACTICAL IMPLEMENTATION OF THE TECHNIQUE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A9 EP A9 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800031 ER PT J AU LITALIEN, GJ LEPPO, JA PAUL, SD HENDEL, RC NEWELL, JB COLEY, C EAGLE, KA AF LITALIEN, GJ LEPPO, JA PAUL, SD HENDEL, RC NEWELL, JB COLEY, C EAGLE, KA TI A SIMPLE SCORING SYSTEM FOR PREOPERATIVE CARDIAC RISK ASSESSMENT IN VASCULAR PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01605. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A380 EP A380 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801505 ER PT J AU MAILHAC, A BADIMON, J MEYER, B FERNANDEZORTIZ, A FUSTER, V BADIMON, L AF MAILHAC, A BADIMON, J MEYER, B FERNANDEZORTIZ, A FUSTER, V BADIMON, L TI EFFECT OF A SEVERE STENOSIS ON FIBRIN(OGEN) DEPOSITION ON SEVERELY DAMAGED VESSEL WALL IN ARTERIAL THROMBOSIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 0 TC 0 Z9 0 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 FEB PY 1994 SI SI BP A41 EP A41 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800160 ER PT J AU MENDES, LA PICARD, MH DEC, GW PALACIOS, IF MAHONEY, D DAVIDOFF, R AF MENDES, LA PICARD, MH DEC, GW PALACIOS, IF MAHONEY, D DAVIDOFF, R TI DISCORDANCE OF RIGHT AND LEFT-VENTRICULAR REMODELING IN ACTIVE MYOCARDITIS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 BOSTON UNIV,MED CTR,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A365 EP A365 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801445 ER PT J AU MEYER, B BADIMON, J FUSTER, V MAILHAC, A FERNANDEZORTIZ, A CHESEBRO, J BADIMON, L AF MEYER, B BADIMON, J FUSTER, V MAILHAC, A FERNANDEZORTIZ, A CHESEBRO, J BADIMON, L TI INHIBITION OF THE PROGRESSION OF THROMBUS GROWTH ON PREEXISTING MURAL THROMBUS - TARGETING OPTIMAL THERAPY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 0 TC 0 Z9 0 U1 0 U2 2 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 FEB PY 1994 SI SI BP A64 EP A64 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800249 ER PT J AU MEYER, B FERNANDEZORTIZ, A FUSTER, V MAILHAC, A DONMICHAEL, T CHESEBRO, J BADIMON, JL BADIMON, J AF MEYER, B FERNANDEZORTIZ, A FUSTER, V MAILHAC, A DONMICHAEL, T CHESEBRO, J BADIMON, JL BADIMON, J TI LOCAL-DELIVERY OF R-HIRUDIN BY A DOUBLE-BALLOON PERFUSION CATHETER INHIBITS PLATELET DEPOSITION POST-ANGIOPLASTY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 FEB PY 1994 SI SI BP A18 EP A18 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800068 ER PT J AU MORENO, PR FUSTER, V PALACIOS, IF FALLON, JT FALK, E AF MORENO, PR FUSTER, V PALACIOS, IF FALLON, JT FALK, E TI INCREASED MACROPHAGE PLAQUE INFILTRATION IN PATIENTS WITH ACUTE CORONARY SYNDROMES SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA 02114. NR 0 TC 0 Z9 0 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 FEB PY 1994 SI SI BP A452 EP A452 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801792 ER PT J AU NEYA, K LEE, R GUERRERO, JL LANG, P VLAHAKES, GJ AF NEYA, K LEE, R GUERRERO, JL LANG, P VLAHAKES, GJ TI EXPERIMENTAL RADIOFREQUENCY-HEATED BALLOON CATHETER ABLATION OF VENTRICULAR OUTFLOW TRACT MUSCLE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A305 EP A305 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801206 ER PT J AU OSSWALD, S WILBER, DUJ LIN, JJ DU, D HOLDEN, HB GARAN, H RUSKIN, JN AF OSSWALD, S WILBER, DUJ LIN, JJ DU, D HOLDEN, HB GARAN, H RUSKIN, JN TI MECHANISM OF SURFACE ECG POLYMORPHISM OF MONOMORPHIC VENTRICULAR-TACHYCARDIA - INSIGHTS FROM SIMULTANEOUS ENDOCARDIAL AND EPICARDIAL ACTIVATION SEQUENCE MAPPING IN A CANINE INFARCT MODEL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A326 EP A326 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801289 ER PT J AU OSSWALD, S TROUTON, TG ONUNAIN, SS ROELKE, M SOSASUAREZ, GE MCGOVERN, BA GARAN, H RUSKIN, JN AF OSSWALD, S TROUTON, TG ONUNAIN, SS ROELKE, M SOSASUAREZ, GE MCGOVERN, BA GARAN, H RUSKIN, JN TI ELECTROCARDIOGRAPHIC PREDICTORS OF HIGH DEFIBRILLATION THRESHOLDS WITH NONTHORACOTOMY CARDIOVERTER-DEFIBRILLATOR LEAD SYSTEMS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A38 EP A38 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800145 ER PT J AU PAUL, SD OGARA, PT BAMEZAI, V HUTTER, AM DESANCTIS, RW EAGLE, KA AF PAUL, SD OGARA, PT BAMEZAI, V HUTTER, AM DESANCTIS, RW EAGLE, KA TI TEMPORAL CHANGES IN THE MANAGEMENT OF ACUTE MYOCARDIAL-INFARCTION BETWEEN THE 1980S AND THE 1990S - ARE WE GETTING MORE AGGRESSIVE WITH THE ELDERLY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 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 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 FEB PY 1994 SI SI BP A438 EP A438 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801737 ER PT J AU PAUL, SD LITALIEN, GJ HENDEL, RC LEPPO, JA EAGLE, KA AF PAUL, SD LITALIEN, GJ HENDEL, RC LEPPO, JA EAGLE, KA TI INFLUENCE OF PRIOR HEART-DISEASE ON MORBIDITY AND MORTALITY AFTER VASCULAR-SURGERY - ROLE OF CORONARY-ARTERY BYPASS-GRAFTING SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01605. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A380 EP A380 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801504 ER PT J AU RIVERA, JM VANDERVOORT, P KARSON, T ARES, M MORRIS, E THOMAS, JD AF RIVERA, JM VANDERVOORT, P KARSON, T ARES, M MORRIS, E THOMAS, JD TI TRICUSPID REGURGITATION JET AREA - PHYSICAL FACTORS INFLUENCING ITS DISPLAY IN THE CLINICAL ENVIRONMENT SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 CLEVELAND CLIN EDUC FDN,CLEVELAND,OH 44106. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI rivera, miguel/D-5026-2014 NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A222 EP A222 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800876 ER PT J AU RODRIGUEZ, A AHUALLI, P BALINO, NP MELE, E PAVIOTTI, C LIPRANDI, MS PALACIOS, I AF RODRIGUEZ, A AHUALLI, P BALINO, NP MELE, E PAVIOTTI, C LIPRANDI, MS PALACIOS, I TI ARGENTINE RANDOMIZED TRIAL OF PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY VERSUS CORONARY-ARTERY BYPASS-SURGERY IN MULTIVESSEL DISEASE (ERACI) - LATE COST AND 3 YEARS FOLLOW-UP RESULTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 ANCHORENA HOSP,BUENOS AIRES,ARGENTINA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A469 EP A469 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801861 ER PT J AU RODRIGUEZ, A SANTAERA, O LARRIBAU, M FERNANDEZ, M RICCITELLI, M BALINO, NP PALACIOS, IF ROUBIN, GS AF RODRIGUEZ, A SANTAERA, O LARRIBAU, M FERNANDEZ, M RICCITELLI, M BALINO, NP PALACIOS, IF ROUBIN, GS TI RATIONAL USE OF CORONARY STENTING TO PREVENT RESTENOSIS - A RANDOMIZED STUDY IN LESIONS WITH EARLY MINIMAL LUMINAL DIAMETER LOSS AFTER PTCA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 ANCHORENA HOSP,BUEONS AIRES,ARGENTINA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV ALABAMA,BIRMINGHAM,AL 35294. NR 0 TC 1 Z9 1 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 FEB PY 1994 SI SI BP A118 EP A118 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800465 ER PT J AU ROELKE, M ONUNAIN, SS TROUTON, TG OSSWALD, S GARAN, H RUSKIN, JN AF ROELKE, M ONUNAIN, SS TROUTON, TG OSSWALD, S GARAN, H RUSKIN, JN TI THE CLINICAL UTILITY AND LIMITATIONS OF STORED ELECTROGRAMS IN DETERMINING THE APPROPRIATENESS OF IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR THERAPY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A419 EP A419 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801661 ER PT J AU ROELKE, M ONUNAIN, SS OSSWALD, S GARAN, H HARTHORNE, JW AF ROELKE, M ONUNAIN, SS OSSWALD, S GARAN, H HARTHORNE, JW TI VENTRICULAR PACING-INDUCED VENTRICULAR-TACHYCARDIA IN PATIENTS WITH IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A323 EP A323 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801278 ER PT J AU SAGIE, A SCHWAMMENTHAL, E PALACIOS, IF KING, MEE WEYMAN, AE LEVINE, RA AF SAGIE, A SCHWAMMENTHAL, E PALACIOS, IF KING, MEE WEYMAN, AE LEVINE, RA TI SIGNIFICANT TRICUSPID REGURGITATION DOES NOT SUBSTANTIALLY RESOLVE AFTER PERCUTANEOUS BALLOON MITRAL VALVULOTOMY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A249 EP A249 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800983 ER PT J AU SAGIE, A PADIAL, LR SCHWAMMENTAHL, E WEYMAN, AE LEVINE, RA AF SAGIE, A PADIAL, LR SCHWAMMENTAHL, E WEYMAN, AE LEVINE, RA TI DETERMINANTS OF FUNCTIONAL TRICUSPID REGURGITATION IN INCOMPLETE TRICUSPID-VALVE CLOSURE - DOPPLER COLOR-FLOW STUDY OF 110 PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A221 EP A221 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800874 ER PT J AU SAGIE, A SCHWAMMENTHAL, E PALACIOS, IF FREITAS, N WEYMAN, AE LEVINE, RA AF SAGIE, A SCHWAMMENTHAL, E PALACIOS, IF FREITAS, N WEYMAN, AE LEVINE, RA TI LEFT-VENTRICULAR FUNCTION IN SIGNIFICANT MITRAL-STENOSIS - ECHOCARDIOGRAPHIC AND HEMODYNAMIC DATA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A32 EP A32 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800124 ER PT J AU SCHWAMMENTHAL, E HE, SQ WEYMAN, AE YOGANATHAN, AP LEVINE, RA FONTAINE, AA AF SCHWAMMENTHAL, E HE, SQ WEYMAN, AE YOGANATHAN, AP LEVINE, RA FONTAINE, AA TI THE IMPACT OF DRIVING PRESSURE ON EFFECTIVE REGURGITANT ORIFICE AREA IN INCOMPLETE MITRAL-VALVE CLOSURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GEORGIA INST TECHNOL,ATLANTA,GA 30332. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A176 EP A176 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800692 ER PT J AU SCHWAMMENTHAL, E HE, SQ FONTAINE, AA NIDORF, SM VLAHAKES, GJ YOGANATHAN, AP WEYMAN, AE LEVINE, RA AF SCHWAMMENTHAL, E HE, SQ FONTAINE, AA NIDORF, SM VLAHAKES, GJ YOGANATHAN, AP WEYMAN, AE LEVINE, RA TI IMPACT OF LEAFLET GEOMETRY ON THE SEVERITY OF MITRAL REGURGITATION IN MITRAL-VALVE PROLAPSE - INSIGHTS FROM AN IN-VITRO MODEL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GEORGIA INST TECHNOL,ATLANTA,GA 30332. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A32 EP A32 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800123 ER PT J AU SOSASUAREZ, GE TROUTON, TG NUNAIN, SS OSSWALD, S PEREZ, I MCGOVERN, BA RUSKIN, JN AF SOSASUAREZ, GE TROUTON, TG NUNAIN, SS OSSWALD, S PEREZ, I MCGOVERN, BA RUSKIN, JN TI RADIOFREQUENCY CATHETER ABLATION FOR VENTRICULAR-TACHYCARDIA NOT ASSOCIATED WITH CORONARY HEART-DISEASE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A35 EP A35 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800136 ER PT J AU SWEENEY, MO RUSKIN, JN VLAHAKES, G DEC, GW AF SWEENEY, MO RUSKIN, JN VLAHAKES, G DEC, GW TI FACTORS ASSOCIATED WITH SUDDEN CARDIAC DEATH IN PATIENTS EVALUATED FOR ORTHOTOPIC CARDIAC TRANSPLANTATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A356 EP A356 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801410 ER PT J AU TOUSSAINT, JF SOUTHERN, JF FUSTER, V KANTOR, HL AF TOUSSAINT, JF SOUTHERN, JF FUSTER, V KANTOR, HL TI COMPARATIVE EFFECTS OF ANGIOPLASTY AND ATHERECTOMY IN HUMAN ATHEROSCLEROTIC PLAQUES STUDIED BY HIGH-FIELD NMR IMAGING SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 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 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 FEB PY 1994 SI SI BP A387 EP A387 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51801530 ER PT J AU VIVALDI, MT GIUGLIANO, RP SAGIE, A PADIAL, L WEYMAN, AE LEVINE, RA SCHWAMMENTHAL, E AF VIVALDI, MT GIUGLIANO, RP SAGIE, A PADIAL, L WEYMAN, AE LEVINE, RA SCHWAMMENTHAL, E TI WHAT IS THE PROGNOSIS OF TRACE AORTIC REGURGITATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A192 EP A192 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800758 ER PT J AU WEISSMAN, NJ PALACIOS, IF WEYMAN, AE AF WEISSMAN, NJ PALACIOS, IF WEYMAN, AE TI DYNAMIC EXPANSION OF CORONARY-ARTERIES - IMPLICATIONS FOR INTRAVASCULAR ULTRASOUND MEASUREMENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A242 EP A242 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800956 ER PT J AU WEISSMAN, NJ NIDORF, SM WEYMAN, AE PICARD, MH AF WEISSMAN, NJ NIDORF, SM WEYMAN, AE PICARD, MH TI OPTIMAL DURATION OF THE STAGES IN DOBUTAMINE STRESS ECHOCARDIOGRAPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1994 SI SI BP A121 EP A121 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800475 ER PT J AU CHEN, CG SIMON, H SCHWAMMENTHAL, E GUERRERO, JL WEYMAN, AE LEVINE, RA AF CHEN, CG SIMON, H SCHWAMMENTHAL, E GUERRERO, JL WEYMAN, AE LEVINE, RA TI IMPACT OF THE SHAPE OF THE PROXIMAL FLOW CONVERGENCE REGION ON THE ACCURACY OF FLOW-RATE CALCULATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 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 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 FEB PY 1994 SI SI BP M108 EP M108 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PP518 UT WOS:A1994PP51800424 ER PT J AU NAGATSU, M ISHIHARA, K ZILE, MR TSUTSUI, H TAGAWA, H DEFREYTE, G TANAKA, R COOPER, G CARABELLO, BA AF NAGATSU, M ISHIHARA, K ZILE, MR TSUTSUI, H TAGAWA, H DEFREYTE, G TANAKA, R COOPER, G CARABELLO, BA TI THE EFFECTS OF COMPLETE VERSUS INCOMPLETE MITRAL-VALVE REPAIR IN EXPERIMENTAL MITRAL REGURGITATION SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID LEFT-VENTRICULAR PERFORMANCE; VOLUME OVERLOAD HYPERTROPHY; CONTRACTILE FUNCTION; CHORDAE TENDINEAE; REPLACEMENT; PRESERVATION; SURGERY; RECONSTRUCTION; CELLS AB Severe mitral regurgitation (regurgitant fraction 0.75 +/- 0.02) was created in eight dogs by our closed-chest chordal rupture technique. After 3 months of chronic mitral regurgitation all indices of contractile function were depressed. Mitral valve repair was then attempted. Postoperative regurgitant fraction was reduced compared with the preoperative value in; all eight dogs. Concomitantly, forward cardiac output increased in all, dogs and pulmonary capillary wedge pressure fell in all dogs. However, in some dogs, significant regurgitation persisted despite repair. Postoperative regurgitant fraction ranged from 0% to 60%. Postoperative residual regurgitant fraction was related significantly to postoperative cardiac output (r = 0.99), pulmonary capillary wedge pressure (r = 0.77), ejection fraction (v 3;0.75), and two indices of contractile function-the mass-corrected end-systolic stress volume relationship (r = 0.87) and end-systolic stiffness (r = 0.93). In general, these parameters returned to their normal values before mitral regurgitation when postoperative regurgitant fraction was less than 30%. Myocytes isolated from the ventricles at the end of study also demonstrated normal contractile function when regurgitant fraction was less than 30%. C1 MED UNIV S CAROLINA,DEPT MED,DIV CARDIOL,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. RI Tsutsui, Hiroyuki/A-4070-2012 FU NHLBI NIH HHS [NHLBI R01 HL38185] NR 32 TC 16 Z9 18 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 FEB PY 1994 VL 107 IS 2 BP 416 EP 423 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA MW492 UT WOS:A1994MW49200010 PM 8302060 ER PT J AU GAISSERT, HA GRILLO, HC MATHISEN, DJ WAIN, JC DEMEESTER, TR TODD, TRJ URSCHEL, HC EGAN, T COOPER, JD AF GAISSERT, HA GRILLO, HC MATHISEN, DJ WAIN, JC DEMEESTER, TR TODD, TRJ URSCHEL, HC EGAN, T COOPER, JD TI TEMPORARY AND PERMANENT RESTORATION OF AIRWAY CONTINUITY WITH THE TRACHEAL T-TUBE SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 73rd Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 25-28, 1993 CL CHICAGO, IL SP AMER ASSOC THORAC SURG ID MANAGEMENT; STENTS AB The advantages of the tracheal T-tube compared with a regular tracheostomy tube are a physiologic direction of air flow, preservation of laryngeal phonation, and superior patient acceptance. Between 1968 and 1991, 140 patients aged 7 months to 95 years underwent placement of T-, TY- (n = 7), or a modified extended T-tube (n = 4). Primary diagnosis was postintubation stenosis in 86 patients, burn injury in 13 patients, malignant airway tumors in 12 patients, and various disorders in 29 patients, Stenting with a silicone rubber tube was temporary in 31 patients and 14 underwent later operative reconstruction. Definitive permanent insertion was performed in 49 patients. A modified tube was used in 4 patients with left main bronchial stenosis with effective long-term palliation in 3. Postoperative airway obstruction prompted placement in 32 patients. Positioning of the T-tube above the vocal cords in 12 patients for subglottic stenosis was effective in 10. The T-tube was not tolerated in 28 patients (20%) because of obstruction of the upper limb or aspiration. Five of 10 patients under the age of 10 years had airway obstruction necessitating tube removal. Long-term intubation in 112 patients exceeded 1 year in 49 patients and 5 years in 12 patients. Only 5 patients required tube removal for obstructive problems more than 2 months after placement. The tracheal T-tube restores airway patency reliably with excellent long-term results and represents the preferred management of chronic airway obstruction not amenable to surgical reconstruction. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN THORAC SURG UNIT,BOSTON,MA 02114. RI DeMeester, Tom/A-4333-2009 NR 12 TC 41 Z9 44 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 FEB PY 1994 VL 107 IS 2 BP 600 EP 606 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA MW492 UT WOS:A1994MW49200033 PM 8302080 ER PT J AU AKINS, CW AF AKINS, CW TI CLINICAL-EVALUATION OF THE OMNISCIENCE CARDIAC-VALVE PROSTHESIS SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Letter RP AKINS, CW (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC SURG UNIT,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD FEB PY 1994 VL 107 IS 2 BP 631 EP 631 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA MW492 UT WOS:A1994MW49200049 ER PT J AU WHITMAN, GJ MCGOVERN, FJ AF WHITMAN, GJ MCGOVERN, FJ TI ENDOMETRIOSIS OF THE BLADDER DETECTED BY PELVIC ULTRASONOGRAPHY SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT UROL,BOSTON,MA 02114. RP WHITMAN, GJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,ACC 2,14 FRUIT ST,BOSTON,MA 02114, USA. NR 8 TC 5 Z9 5 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 FEB PY 1994 VL 13 IS 2 BP 155 EP 157 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA MX027 UT WOS:A1994MX02700018 PM 7932963 ER PT J AU LAMURAGLIA, GM CHANDRASEKAR, NR FLOTTE, TJ ABBOTT, WM MICHAUD, N HASAN, T AF LAMURAGLIA, GM CHANDRASEKAR, NR FLOTTE, TJ ABBOTT, WM MICHAUD, N HASAN, T TI PHOTODYNAMIC THERAPY INHIBITION OF EXPERIMENTAL INTIMAL HYPERPLASIA - ACUTE AND CHRONIC EFFECTS SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the Society-for-Vascular-Surgery CY JUN 08-09, 1993 CL WASHINGTON, DC SP SOC VASC SURG ID MUSCLE CELL-PROLIFERATION; VASCULAR INJURY; ARTERIAL INJURY; LESIONS AB Purpose: Intimal hyperplasia (IH) is a focal arterial problem that still eludes successful therapy. We have previously demonstrated the feasibility of use of photodynamic therapy (PDT) for the acute treatment of experimental IH with light to activate an otherwise biologically inert photosensitizer. The purpose of this study was to determine the acute and long-term effects of PDT inhibition of IH on the artery wall. Methods: Segmental IH was induced by balloon injury localized to the cervical common carotid artery of 33 rats. The photosensitizer chloroaluminum sulfonated phthalocyanine (5 mg/kg) for the experimental group or saline solution for the control group was administered intravenously. Twenty-four hours later, all instrumented portions of arteries were irradiated at 675 nm to induce cytotoxic injury in the PDT-treated arteries as compared with laser only-treated arteries for controls. Animals were killed at 1, 2, 4, and 16 weeks. Results: There were no untoward side effects in either group. All PDT-treated arteries were devoid of smooth muscle or inflammatory cells in the treated media. There was no evidence of arterial degeneration of PDT-treated arteries. Only three arteries in the PDT group developed IH, whereas it was universal in all controls. In control arteries, immunocytochemistry with bromodeoxyuridine revealed maximal intimal and medial cell proliferation at 1 week, and morphometric analysis demonstrated a maximal IH at 2 weeks. Immunocytochemistry staining for smooth muscle cell actin was positive for the IH in control and when present in PDT-treated arteries, whereas the adventitia of PDT-heated arteries were positive after 2 weeks. Electron microscopy demonstrated early myofibroblast migration to the adventitia, and at 16 weeks occasional myofibroblasts were noted in the media of PDT-treated arteries. There was complete reendothelial cell covering of the intima by 4 weeks. Conclusions: These in vivo data demonstrate that PDT is an effective local method for the treatment of experimental IH. There is no evidence of significant recurrence of IH or arterial degeneration. Further studies with PDT may provide novel approaches to the understanding and treatment of arterial IH. C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP LAMURAGLIA, GM (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,WELLMAN LABS PHOTOMED,DIV VASC SURG,FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-02583] NR 22 TC 55 Z9 59 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 FEB PY 1994 VL 19 IS 2 BP 321 EP 331 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA MW751 UT WOS:A1994MW75100014 PM 8114192 ER PT J AU THALI, M CHARLES, M FURMAN, C CAVACINI, L POSNER, M ROBINSON, J SODROSKI, J AF THALI, M CHARLES, M FURMAN, C CAVACINI, L POSNER, M ROBINSON, J SODROSKI, J TI RESISTANCE TO NEUTRALIZATION BY BROADLY REACTIVE ANTIBODIES TO THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 GLYCOPROTEIN CONFERRED BY A GP41 AMINO-ACID CHANGE SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; CD4 RECEPTOR-BINDING; HTLV-III; ENVELOPE GLYCOPROTEIN; POINT MUTATION; T4 MOLECULE; AIDS; HIV-1; SITE; INFECTION AB A neutralization-resistant variant of human immunodeficiency virus type 1 (HIV-1) that emerged during in vitro propagation of the virus in the presence of neutralizing serum from an infected individual has been described. A threonine-for-alanine substitution at position 582 in the gp41 transmembrane envelope glycoprotein of the variant virus was responsible for the neutralization-resistant phenotype (M.S. Reitz, Jr., C. Wilson, C. Naugle, R C. Gallo, and M. Robert-Guroff, Cell 54:57-63, 1988). The mutant virus also exhibited reduced sensitivity to neutralization by 30% of HIV-1-positive sera that neutralized the parental virus, suggesting that a significant fraction of the neutralizing activity within these sera can be affected by the amino acid change in gp41 (C. Wilson, M. S. Reitz, Jr., K. Aldrich, P. J. Klasse, J. Blomberg, R. C. Gallo, and M. Robert-Guroff, J. Virol. 64:3240-3248, 1990). It is shown here that the change of alanine 582 to threonine specifically confers resistance to neutralization by antibodies directed against bath groups of discontinuous, conserved epitopes related to the CD4 binding site on the gp120 exterior envelope glycoprotein. Only minor differences in binding of these antibodies to wild-type and mutant envelope glycoproteins were observed. Thus, the antigenic structure of gp120 can be subtly affected by an amino acid change in gp41, with important consequences for sensitivity to neutralization. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV CONNECTICUT,HLTH SERV,DEPT PEDIAT,FARMINGTON,CT 06030. FU NCI NIH HHS [CA 06516]; NIAID NIH HHS [AI24030, AI31783] NR 49 TC 61 Z9 61 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 FEB PY 1994 VL 68 IS 2 BP 674 EP 680 PG 7 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200013 PM 7507184 ER PT J AU GONCALVES, J JALLEPALLI, P GABUZDA, DH AF GONCALVES, J JALLEPALLI, P GABUZDA, DH TI SUBCELLULAR-LOCALIZATION OF THE VIF PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF VIROLOGY LA English DT Article ID SOR GENE-PRODUCT; HTLV-III/LAV; ENDOPLASMIC-RETICULUM; MICROSOMAL-MEMBRANES; PLASMA-MEMBRANE; SEQUENCE; HIV-1; IDENTIFICATION; TRANSCRIPTION; TRANSLOCATION AB The Vif (viral infectivity factor) protein of human immunodeficiency virus type 1 (HIV-1) has been shown to dramatically enhance the infectivity of HIV-1 virus particles during virus production. The subcellular localization of Vif was examined to elucidate cellular pathways which may be important far Vif function. Indirect immunofluorescence staining of Vif demonstrated a diffuse cytoplasmic distribution and showed that most Vif was not associated with the Golgi complex, a proposed site of localization (B. Guy, M. Geist, K. Dott, D. Spehner, M.-P. Kieny, and J.-P. Lecocq, J. Virol. 65:1325-1331, 1991). Subcellular fractionation of transfected COS cells and HIV-1-infected Jurkat and CEM cells demonstrated that Vif is a cytoplasmic protein which exists in both a soluble cytosolic form and membrane-associated form. The membrane-associated form of Vif is a peripheral membrane protein which is tightly associated with the cytoplasmic side of cellular membranes. The C terminus of Vif was required for the stable association of Vif with membranes. The C terminus was also essential for Vif function, suggesting that the association of Vif with membranes is likely to be important for its biological activity. The highly conserved regions at residues 103 to 115 and 142 to 150 were important for Vif function but did not affect membrane association, indicating that these regions are likely to be important for other, as-yet-unknown functions. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RI iMed.ULisboa, iMed.ULisboa/C-6292-2014; Goncalves, Joao/B-2013-2008; iMed.ULisboa, M2B /B-5277-2014 OI Goncalves, Joao/0000-0002-1245-3715; FU NIAID NIH HHS [AI01017, AI28691, AI33837] NR 51 TC 115 Z9 117 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 1994 VL 68 IS 2 BP 704 EP 712 PG 9 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200017 PM 8289374 ER PT J AU FOUREL, I SAPUTELLI, J SCHAFFER, P MASON, WS AF FOUREL, I SAPUTELLI, J SCHAFFER, P MASON, WS TI THE CARBOCYCLIC ANALOG OF 2'-DEOXYGUANOSINE INDUCES A PROLONGED INHIBITION OF DUCK HEPATITIS-B VIRUS-DNA SYNTHESIS IN PRIMARY HEPATOCYTE CULTURES AND IN THE LIVER SO JOURNAL OF VIROLOGY LA English DT Article ID CHRONICALLY INFECTED DUCKS; REVERSE-TRANSCRIPTASE; PYRIMIDINE NUCLEOSIDES; ENVELOPE PROTEINS; CARRIER STATE; VIRAL-DNA; INVITRO; HEPADNAVIRUS; REPLICATION; SERUM AB The carbocyclic analog of 2'-deoxyguanosine (2'-CDG) is a strong inhibitor of hepatitis B virus (HBV) DNA synthesis in HepG2 cells (P. M. Price, R. Banerjee, and G. Acs, Proc. Natl. Acad. USA 86:8543-8544, 1989). We now report that 2'-CDG inhibited duck hepatitis B virus (DHBV) DNA synthesis in primary cultures of duck hepatocytes and in experimentally infected ducks. Like foscarnet (phosphonoformic acid [PFA]) and 2'-,3'-dideoxycytidine (ddC), 2'-CDG blocked viral DNA replication in primary hepatocyte cultures when present during an infection but failed to inhibit the DNA repair reaction that occurs during the initiation of infection to convert virion relaxed circular DNA to covalently closed circular DNA, the template for viral mRNA transcription. Moreover, as for PFA and ddC, viral RNA synthesis was detected when infection was initiated in the presence 2'-CDG. In another respect, however, 2'-CDG exhibited antiviral activity unlike that of ddC or PFA: a single 1-day treatment of hepatocytes with 2'-CDG blocked initiation of viral DNA synthesis for at least 8 days, irrespective of whether DHBV infection was carried out at the time of drug treatment or several days later. Furthermore, orally administered 2'-CDG was long-acting against DHBV in experimentally infected ducklings. Virus replication was delayed by up to 4 days in ducklings infected after administration of 2'-CDG. These observations bf long-lasting efficacy in vitro and in vivo even after oral administration suggest that this inhibitor or a nucleoside with similar pharmacological properties may be ideal for reducing virus replication in patients with chronic HBV infection. C1 FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. DANA FARBER CANC INST,BOSTON,MA 02115. VIRACHEM INC,BOSTON,MA 02115. FU NCI NIH HHS [CA-06927]; NCRR NIH HHS [RR-05539]; NIAID NIH HHS [AI-18641] NR 39 TC 46 Z9 46 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 FEB PY 1994 VL 68 IS 2 BP 1059 EP 1065 PG 7 WC Virology SC Virology GA MW252 UT WOS:A1994MW25200055 PM 8289335 ER PT J AU URENA, P KUBRUSLY, M MANNSTADT, M HRUBY, M TAN, MMTT SILVE, C LACOUR, B ABOUSAMRA, AB SEGRE, GV DRUEKE, T AF URENA, P KUBRUSLY, M MANNSTADT, M HRUBY, M TAN, MMTT SILVE, C LACOUR, B ABOUSAMRA, AB SEGRE, GV DRUEKE, T TI THE RENAL PTH PTHRP RECEPTOR IS DOWN-REGULATED IN RATS WITH CHRONIC-RENAL-FAILURE SO KIDNEY INTERNATIONAL LA English DT Note ID PARATHYROID-HORMONE RECEPTORS; ADENYLATE CYCLASE SYSTEM; SKELETAL RESISTANCE; CELL-LINE; REVERSIBLE RESISTANCE; AGED RATS; HYPERPARATHYROIDISM; DESENSITIZATION; CALCIUM; MEMBRANES AB Hypocalcemia, hyperphosphatemia, and resistance to the action of PTH are well characterized features in the setting of advanced chronic renal failure (CRF). Although the underlying mechanisms are ill-understood, clinical and experimental evidence points to both PTH receptor down-regulation and post-receptor abnormalities in their pathogenesis. In the present study we have examined the effect of advanced CRF in rats on the renal expression of PTH/PTHrP receptor (PTH-R). CRF was created by a standard two-step operation (5/6 nephrectomy). Four weeks thereafter, 19 uremic rats were compared with 23 sham-operated rats. Uremic rats had higher mean (+/- SD) plasma creatinine levels than control rats, 164 +/- 107 mum versus 43 +/- 5 mum, respectively. They also had higher plasma phosphorus and iPTH levels, 4.70 +/- 1.71 mm versus 2.59 +/- 0.37 mm and 561 +/- 336 versus 27 +/- 18 pg/ml, respectively. Mean plasma total calcium and blood ionized calcium were significantly lower in uremic than in control rats, 2.13 +/- 0.06 mm versus 2.61 +/- 0. 10 mm and 1.07 +/- 0. 11 versus 1.31 +/- 0.06 mm, respectively. Mean plasma calcitriol concentration was also significantly lower in uremic than in control rats, 39.8 +/- 14.6 and 80.4 +/- 15.2 pg/ml, respectively. Nine out of the 19 rats were examined for renal PTH-R gene expression. We show for the first time that the level of PTH-R mRNA in the kidney of uremic rats was markedly decreased compared with that of normal rats, the ratio PTH-R mRNA/beta-actin mRNA being 0.47 +/- 0.12 versus 0.99 +/- 0.23, respectively, and the ratio PTH-R mRNA/28S being 8.9 +/- 4.7 versus 19.6 +/- 11.1, respectively. This decrease was associated with a marked reduction in PTH-sensitive adenylyl cyclase activity in crude renal membranes from uremic rats. The values of basal adenylyl cyclase activity and subsequently after stimulation by forskolin and NaF were also significantly reduced in comparison to that of normal rats. These data indicate that rats with severe CRF have reduced renal PTH-R expression, associated with diminished basal and PTH-sensitive adenylyl cyclase activity. These abnormalities could be important in the pathogenesis of the secondary hyperparathyroidism of CRF. C1 HOP NECKER ENFANTS MALAD,DEPT NEPHROL,F-75730 PARIS 15,FRANCE. HOP NECKER ENFANTS MALAD,CNRS,F-75730 PARIS 15,FRANCE. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. RP URENA, P (reprint author), HOP NECKER ENFANTS MALAD,INSERM,UNITE 90,161 RUE SEVRES,F-75743 PARIS 15,FRANCE. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 43 TC 121 Z9 123 U1 1 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 FEB PY 1994 VL 45 IS 2 BP 605 EP 611 DI 10.1038/ki.1994.79 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA MR136 UT WOS:A1994MR13600042 PM 8164450 ER PT J AU KROLEWSKI, AS WARRAM, JH CHRISTLIEB, AR AF KROLEWSKI, AS WARRAM, JH CHRISTLIEB, AR TI HYPERCHOLESTEROLEMIA-A DETERMINANT OF RENAL-FUNCTION LOSS AND DEATHS IN IDDM PATIENTS WITH NEPHROPATHY SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Satellite Symposium on Progression of Renal Disease CY JUN 20-22, 1993 CL TIBERIAS, ISRAEL ID DEPENDENT DIABETES-MELLITUS; CORONARY-ARTERY DISEASE; PERSISTENT PROTEINURIA; METABOLIC CONTROL; EXCESS MORTALITY; NATURAL-HISTORY; BLOOD-PRESSURE; HEART-DISEASE; PIMA-INDIANS; HYPERTENSION AB The development of kidney disease in diabetes mellitus can be viewed as a two-stage process: (1) the development of proteinuria, and (2) its progression to chronic renal failure. Determinants of the latter were examined in 439 IDDM patients who had nephropathy and participated in the Diabetic Retinopathy Study. Using serum creatinine levels obtained during the follow-up period to assess the rate of loss of renal function, we found that only one-third of these patients experienced a rapid loss of function, while the others had slowly declining or unchanging renal function despite the presence of proteinuria and severe diabetic retinopathy. Among the many baseline variables examined, only elevated cholesterol and elevated systemic blood pressure were predictors of a rapid loss of renal function. Patients with this rapid loss of renal function also had the highest risk of death due to cardiovascular causes, as well as all causes. Once again, hypercholesterolemia was the major predictor of these deaths. In conclusion, efforts should be undertaken early to identify patients who are rapidly losing renal function so that interventions to modify systemic blood pressure and hypercholesterolemia may prevent or postpone the development of renal failure and death in patients with IDDM. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP KROLEWSKI, AS (reprint author), JOSLIN DIABET CTR,DIV RES,EPIDEMIOL & GENET SECT,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK 41526] NR 40 TC 94 Z9 96 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD FEB PY 1994 VL 45 SU 45 BP S125 EP S131 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA MR867 UT WOS:A1994MR86700032 PM 8158881 ER PT J AU BUSQUE, L ILARIA, R TANTRAVAHI, R WEINSTEIN, H GILLILAND, DG AF BUSQUE, L ILARIA, R TANTRAVAHI, R WEINSTEIN, H GILLILAND, DG TI CLONALITY ANALYSIS OF CHILDHOOD ALL IN REMISSION - NO EVIDENCE OF CLONAL HEMATOPOIESIS SO LEUKEMIA RESEARCH LA English DT Article DE CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA; CLONALITY; PGK; PCR; CYTOGENETICS ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; X-CHROMOSOME INACTIVATION; ACUTE MYELOID-LEUKEMIA; CELL SELF-RENEWAL; DIFFERENTIATION; CHILDREN; MARROW AB We studied 98 female patients in remission (2-240 months) from childhood ALL to determine the clonality status of their hematopoiesis. Thirty-one (31.6%) were heterozygous at the PGK locus for the BstX1 endonuclease restriction site, permitting X-linked clonality assays to be performed. Two patients were in relapse at the time of study and were excluded. We used the PGK-PCR clonality assay (PPCA) to analyze DNA from PMN and mononuclear cells of the remaining 29 female patients. All (29/29) patients demonstrated polyclonal hematopoiesis. These data show that remission from childhood ALL involves reestablishment of polyclonally derived hematopoiesis in all patients studied. C1 DANA FARBER CANC INST,BOSTON,MA 02115. CHILDRENS HOSP,BOSTON,MA 02115. RP BUSQUE, L (reprint author), BRIGHAM & WOMENS HOSP,LONGWOOD MED RES CTR,DIV HEMATOL ONOCOL,R219,221 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA57261-01] NR 22 TC 5 Z9 5 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 FEB PY 1994 VL 18 IS 2 BP 71 EP 77 DI 10.1016/0145-2126(94)90121-X PG 7 WC Oncology; Hematology SC Oncology; Hematology GA MW668 UT WOS:A1994MW66800001 PM 8107490 ER PT J AU EMANUEL, LL BARRY, MJ EMANUEL, EJ STOECKLE, JD AF EMANUEL, LL BARRY, MJ EMANUEL, EJ STOECKLE, JD TI ADVANCE DIRECTIVES - CAN PATIENTS STATED TREATMENT CHOICES BE USED TO INFER UNSTATED CHOICES SO MEDICAL CARE LA English DT Article DE ADVANCE DIRECTIVES; PREDICTING DECISIONS; SUBSTITUTED JUDGMENTS; TREATMENT INSTRUCTIONS ID HEALTH-CARE; PREFERENCES; DECISIONS; PROXIES; LIFE; PREDICTIONS; RESIDENTS AB Advance directives have been widely endorsed as a method to match medical interventions to patients' preferences. However, applying advance directives to unspecified future decisions may be problematic. We wondered how well scenario-based treatment choices in advance directives can be used to infer other choices specified by the same patients. We asked 495 out-patients from the Massachusetts General Hospital to state 11 treatment choices in each of four illness scenarios. We calculated likelihood ratios (LRs) to see how well one choice could predict another. Predictions within a given scenario were strong and followed a pattern that reflected the invasiveness of the treatment. Thus, decline of antibiotics predicted decline of major surgery, in the same scenario (LR 36.0-108.3). Requests for major surgery strongly predicted requests for antibiotics (LR 90.4 - 244.1). Requests for major surgery and decline of antibiotics were the two most predictive preferences; more traditionally considered decisions about cardiopulmonary resuscitation and mechanical ventilation ranged from the third to ninth most predictive among the 11 interventions. Predictions between scenarios were weaker, but still potentially useful, and followed a pattern that reflected the prognoses of the scenarios. Declining treatment in the best prognosis scenario (coma-with-a-chance) predicted declining the same treatment in other scenarios with LRs of 2.5-6.1. Requests for treatment in the worst prognosis scenario (dementia-with-terminal-illness) predicted the same request in the other scenarios with LRs of 5.2-30.5. These data suggest that patients' advance scenario-based treatment choices can provide potentially useful information to apply to unspecified decisions if inferences follow considerations of prognosis and treatment invasiveness. For maximal predictive power, treatment directives should use a range of illness scenarios and include choices, among several others, on antibiotic use and major surgery. C1 HARVARD UNIV,SCH MED,DIV MED ETH,BOSTON,MA. DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA. RP EMANUEL, LL (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114, USA. FU AHRQ HHS [R01 HS06120] NR 32 TC 40 Z9 40 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD FEB PY 1994 VL 32 IS 2 BP 95 EP 105 DI 10.1097/00005650-199402000-00001 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA MV785 UT WOS:A1994MV78500001 PM 8302111 ER PT J AU JAHROUDI, N LYNCH, DC AF JAHROUDI, N LYNCH, DC TI ENDOTHELIAL-CELL-SPECIFIC REGULATION OF VON-WILLEBRAND-FACTOR GENE-EXPRESSION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN VONWILLEBRAND-FACTOR; BETA-GLOBIN GENE; TRANSCRIPTION INITIATION SITE; GATA-BINDING PROTEIN; 5'-FLANKING REGION; FINGER PROTEIN; DNA-BINDING; ELEMENTS; IDENTIFICATION; ENHANCER AB In both tissue sections and cell culture, the endothelial nature of a cell is most commonly determined by demonstration of its expression of von Willebrand factor (vWf) protein and/or mRNA. Thus, the mechanism of cell-type-specific transcriptional regulation of the vWf gene is central to studying the basis of endothelial-cell-specific gene expression. In this study, deletion analyses were carried out to identify the region of the vWf gene which regulates its endothelial-cell-specific expression. A 734-bp fragment which spans the sequence from -487 to +247 relative to the transcription start site was identified as the cell-type-specific promoter. It consists of a minimal core promoter located between -90 and +22, a strong negative regulatory element located upstream of the core promoter (ca. -500 to -300), and a positive regulatory region located downstream of the core promoter in the first exon. The activity of the core promoter is not cell type specific, and the negative regulatory region is required to inhibit its activity in all cell types. This positive regulatory region relieves this inhibition only in endothelial cells and results in endothelial-cell-specific gene expression. The positive regulatory region contains sequences predicting possible SP1, GATA, and octamer binding sites. Mutations in either the SP1 or octamer sequence have no effect on transcriptional activity, while mutation in the GATA binding element totally abolishes the promoter activity. Evidence that a GATA factor is involved in this interaction is presented. Thus, the positive regulatory region with an intact GATA binding site is required to overcome the inhibitory effect of the negative regulatory element and activate vWf gene expression in an endothelial-cell-specific manner. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 33014] NR 56 TC 99 Z9 101 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 FEB PY 1994 VL 14 IS 2 BP 999 EP 1008 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NK734 UT WOS:A1994NK73400015 PM 7507210 ER PT J AU HSU, HL HUANG, L TSAN, JT FUNK, W WRIGHT, WE HU, JS KINGSTON, RE BAER, R AF HSU, HL HUANG, L TSAN, JT FUNK, W WRIGHT, WE HU, JS KINGSTON, RE BAER, R TI PREFERRED SEQUENCES FOR DNA RECOGNITION BY THE TAL1 HELIX-LOOP-HELIX PROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID T-CELL LEUKEMIA; GLUTATHIONE-S-TRANSFERASE; ENHANCER-BINDING; CYCLIC AMPLIFICATION; ESCHERICHIA-COLI; GENE; TRANSLOCATION; MOTIF; SITE; COMPLEXES AB Tumor-specific activation of the TAL1 gene is the most common genetic alteration seen in patients with T-cell acute lymphoblastic leukemia. The TAL1 gene products contain the basic helix-loop-helix (bHLH) domain, a protein dimerization and DNA-binding motif common to several known transcription factors. A binding-site selection procedure has now been used to evaluate the DNA recognition properties of TAL1. These studies demonstrate that TAL1 polypeptides do not have intrinsic DNA-binding activity, presumably because of their inability to form bHLH homodimers. However, TAL1 readily interacts with any of the known class A bHLH proteins (E12, E47, E2-2, and HEB) to form heterodimers that bind DNA in a sequence-specific manner. The TAL1 heterodimers preferentially recognize a subset of E-box elements (CANNTG) that can be represented by the consensus sequence AACAGATGGT. This consensus is composed of half-sites for recognition by the participating class A bHLH polypeptide (AACAG) and the TAL1 polypeptide (ATGGT). TAL1 heterodimers with DNA-binding activity are readily detected in nuclear extracts of Jurkat, a leukemic cell line derived from a patient with T-Cell acute lymphoblastic leukemia. Hence, TAL1 is likely to bind a regulate the transcription of unique subset of subordinate target genes, some of which may mediate the malignant function of TAL1 during T-cell leukemogenesis. C1 UNIV TEXAS,SW MED CTR,DEPT MICROBIOL,DALLAS,TX 75235. UNIV TEXAS,SW MED CTR,DEPT CELL BIOL,DALLAS,TX 75235. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. FU NCI NIH HHS [CA46593] NR 48 TC 149 Z9 149 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD FEB PY 1994 VL 14 IS 2 BP 1256 EP 1265 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NK734 UT WOS:A1994NK73400041 PM 8289805 ER PT J AU FOTUHI, M STANDAERT, DG TESTA, CM PENNEY, JB YOUNG, AB AF FOTUHI, M STANDAERT, DG TESTA, CM PENNEY, JB YOUNG, AB TI DIFFERENTIAL EXPRESSION OF METABOTROPIC GLUTAMATE RECEPTORS IN THE HIPPOCAMPUS AND ENTORHINAL CORTEX OF THE RAT SO MOLECULAR BRAIN RESEARCH LA English DT Article DE METABOTROPIC GLUTAMATE RECEPTOR; HIPPOCAMPUS; ENTORHINAL CORTEX; PHOSPHOINOSITIDE-LINKED RECEPTOR; EXCITOTOXICITY ID LONG-TERM POTENTIATION; EXCITATORY AMINO-ACIDS; PROTEIN KINASE-C; SIGNAL TRANSDUCTION; BRAIN; LOCALIZATION; STIMULATION; SLICES; HYDROLYSIS; INDUCTION AB Metabotropic glutamate receptors (mGluRs) have been implicated in a number of hippocampal functions including learning and memory. Five subtypes have been molecularly and pharmacologically characterized. Using in situ hybridization with oligonucleotide probes selective for these five mGluRs, we have found that each has a unique pattern of expression in the hippocampus and entorhinal cortex. mGluR1 is expressed predominantly in the dentate gyrus and CA3. mGluR2 is enriched in the dentate gyrus and inner layer of the entorhinal cortex. mGluR3 is also expressed in these two structures, but unlike all the other mGluRs, is found in white matter areas as well. mGluR4 is present predominantly in CA2 while mGluR5 is concentrated in most regions of the hippocampus and entorhinal cortex. Comparative analysis of the distributions of these receptors with that of the components of their putative downstream signal transduction mechanisms suggests that mGluR5 may be the main subtype of mGluR which mediates the excitatory actions of glutamate in CA1 and could contribute to the elevation of calcium levels found in CA1 pyramidal neurons in long term potentiation and in ischemic/hypoxic injury. mGluR2 and mGluR3, the main subtypes contributing to the inhibitory actions of glutamate, are absent in CA1. Thus, the mGluR-mediated excitatory actions of glutamate can occur in all regions of the hippocampus whereas the mGluR-mediated inhibitory actions of glutamate may be restricted to the dentate gyrus and CA3. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. UNIV MICHIGAN, NEUROSCI PROGRAM, ANN ARBOR, MI 48109 USA. OI Fotuhi, Majid/0000-0002-0980-1176; Standaert, David/0000-0003-2921-8348 NR 42 TC 101 Z9 104 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB PY 1994 VL 21 IS 3-4 BP 283 EP 292 DI 10.1016/0169-328X(94)90259-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA MV342 UT WOS:A1994MV34200011 ER PT J AU BORSOOK, D KONRADI, C FALKOWSKI, O COMB, M HYMAN, SE AF BORSOOK, D KONRADI, C FALKOWSKI, O COMB, M HYMAN, SE TI MOLECULAR MECHANISMS OF STRESS-INDUCED PROENKEPHALIN GENE-REGULATION - CREB INTERACTS WITH THE PROENKEPHALIN GENE IN THE MOUSE HYPOTHALAMUS AND IS PHOSPHORYLATED IN RESPONSE TO HYPEROSMOLAR STRESS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CYCLIC-AMP; MESSENGER-RNA; SUPRAOPTIC NUCLEI; TRANSCRIPTION; FOS; EXPRESSION; ENHANCER; PROTEINS; ELEMENT; CALCIUM AB We have established a transgenic model to facilitate the study of stress-induced gene regulation in the hypothalamus. This model, which uses a human proenkephalin-beta-galactosidase fusion gene, readily permits anatomic and cellular colocalization of stress-regulated immediate early gene products (e.g. Fos) and other transcription factors [e.g. cAMP response element-binding protein (CREB)] with the product of a potential target gene. Moreover, Fos provides a marker of cellular activation that is independent of the transgene. Hypertonic saline stress induced Fos in almost all cells in the PVN that exhibited basal expression of the proenkephalin transgene; however, all cells in which the transgene was activated by stress also expressed Fos. CREB was found in essentially all neurons. Gel shift analysis with and without antisera to Fos and CREB showed that AP-1 binding activity, containing Fos protein, was induced by hyperosmotic stress. However, Fos was not detected binding to the proenkephalin second messenger-inducible enhancer even in hypothalamic cell extracts from stressed animals. In contrast, CREB formed specific complexes with both the proenkephalin enhancer and a cAMP- and calcium-regulated element (CaRE) within the c-fos gene. Moreover, we found that hypertonic saline induced CREB phosphorylation in cells that express the transgene within the paraventricular nucleus and supraoptic nucleus. These results suggest a model in which proenkephalin gene expression in the paraventricular nucleus is regulated by CREB in response to hypertonic stress. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, MOLEC & DEV NEUROSCI LAB, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT ANESTHESIA, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02114 USA. FU NIDA NIH HHS [R01 DA007134, R01 DA007134-09, DA-07134]; NIMH NIH HHS [MH-00892, MH-44160] NR 23 TC 78 Z9 81 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD FEB PY 1994 VL 8 IS 2 BP 240 EP 248 DI 10.1210/me.8.2.240 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MX286 UT WOS:A1994MX28600012 PM 8170480 ER PT J AU BIANCHI, AB HARA, T RAMESH, V GAO, JZ KLEINSZANTO, AJP MORIN, F MENON, AG TROFATTER, JA GUSELLA, JF SEIZINGER, BR KLEY, N AF BIANCHI, AB HARA, T RAMESH, V GAO, JZ KLEINSZANTO, AJP MORIN, F MENON, AG TROFATTER, JA GUSELLA, JF SEIZINGER, BR KLEY, N TI MUTATIONS IN TRANSCRIPT ISOFORMS OF THE NEUROFIBROMATOSIS-2 GENE IN MULTIPLE HUMAN TUMOR TYPES SO NATURE GENETICS LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; BREAST-CANCER; CHROMOSOME-22; NF2; RETINOBLASTOMA; HETEROZYGOSITY; HETEROGENEITY; EXPRESSION; CARCINOMA; POLYPOSIS AB The neurofibromatosis 2 gene (NF2) has recently been isolated and predicted to encode a novel protein related to the moesin-ezrin-radixin family of cytoskeleton-associated proteins. Here we describe a novel isoform of the NF2 transcript that shows differential tissue expression and encodes a modified C terminus of the predicted protein. Mutations affecting both isoforms of the NF2 transcript were detected in multiple tumour types including melanoma and breast carcinoma. These findings provide evidence that alterations in the NF2 transcript occur not only in the hereditary brain neoplasms typically associated with NF2, but also as somatic mutations in their sporadic counterparts and in seemingly unrelated tumour types. The NF2 gene may thus constitute a tumour suppressor gene of more general importance in tumorigenesis. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. UNIV CINCINNATI,MED CTR,DEPT MOLEC GENET,CINCINNATI,OH 45267. RP BIANCHI, AB (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,DEPT MOLEC GENET & CELL BIOL,ONCOL DRUG DISCOVERY,PRINCETON,NJ 08543, USA. RI Klein-Szanto, Andres/E-6218-2010 FU NHGRI NIH HHS [HG00016, HG00317]; NINDS NIH HHS [NS24279] NR 34 TC 197 Z9 202 U1 0 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD FEB PY 1994 VL 6 IS 2 BP 185 EP 192 DI 10.1038/ng0294-185 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA MU763 UT WOS:A1994MU76300015 PM 8162073 ER PT J AU HOCH, DB HILL, RA OAS, KH AF HOCH, DB HILL, RA OAS, KH TI EPILEPSY AND MENTAL DECLINE SO NEUROLOGIC CLINICS LA English DT Article ID CAUSE INTELLECTUAL DETERIORATION; TONIC-CLONIC SEIZURES; STATUS EPILEPTICUS; ELECTROCONVULSIVE-THERAPY; COGNITIVE IMPAIRMENT; CHILDREN; INTELLIGENCE; PERFORMANCE; MEMORY; ADULTS C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,EPILEPSY PROGRAM,BOSTON,MA 02114. RP HOCH, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,EPILEPSY SERV,BURNHAM 8,FRUIT ST,BOSTON,MA 02114, USA. OI Hoch, Daniel/0000-0002-4294-024X NR 73 TC 10 Z9 10 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD FEB PY 1994 VL 12 IS 1 BP 101 EP 113 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA MY352 UT WOS:A1994MY35200008 PM 8183204 ER PT J AU CUMMINGS, JL HEGARTY, A AF CUMMINGS, JL HEGARTY, A TI NEUROLOGY, PSYCHIATRY, AND NEUROPSYCHIATRY SO NEUROLOGY LA English DT Editorial Material ID DISORDERS; MOOD C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT PSYCHIAT & BIOBEHAV SCI, LOS ANGELES, CA USA. W LOS ANGELES VET AFFAIRS MED CTR, PSYCHIAT SERV, BEHAV NEUROSCI SECT, LOS ANGELES, CA USA. ALBERT EINSTEIN COLL MED, DEPT PSYCHIAT, BRONX, NY USA. ALBERT EINSTEIN COLL MED, DEPT NEUROL, BRONX, NY USA. RP CUMMINGS, JL (reprint author), UNIV CALIF LOS ANGELES, SCH MED, REED NEUROL RES CTR, DEPT NEUROL, 710 WESTWOOD PLAZA, LOS ANGELES, CA 90024 USA. FU NIA NIH HHS [AG10123] NR 31 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1994 VL 44 IS 2 BP 209 EP 213 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA MW890 UT WOS:A1994MW89000003 PM 8309560 ER PT J AU BRESSMAN, SB HEIMAN, GA NYGAARD, TG OZELIUS, LJ HUNT, AL BRIN, MF GORDON, MF MOSKOWITZ, CB DELEON, D BURKE, RE FAHN, S RISCH, NJ BREAKEFIELD, XO KRAMER, PL AF BRESSMAN, SB HEIMAN, GA NYGAARD, TG OZELIUS, LJ HUNT, AL BRIN, MF GORDON, MF MOSKOWITZ, CB DELEON, D BURKE, RE FAHN, S RISCH, NJ BREAKEFIELD, XO KRAMER, PL TI A STUDY OF IDIOPATHIC TORSION DYSTONIA IN A NON-JEWISH FAMILY - EVIDENCE FOR GENETIC-HETEROGENEITY SO NEUROLOGY LA English DT Article ID DOPA-RESPONSIVE DYSTONIA; LINKAGE ANALYSIS; ASHKENAZI JEWS; PARKINSONISM; REGION; LOCUS; EXCLUSION; 9Q32-34 AB A gene (DYT1) for idiopathic torsion dystonia (ITD) was mapped to chromosome 9q34 in non-Jewish and Jewish families; the dystonia in these families usually began in childhood, with the limb muscles affected first. The role of the DYT1 gene in adult-onset and cervical- or cranial-onset ITD is unknown. We examined 53 individuals from four generations of a non-Jewish North American family with adult-onset ITD. There were seven affected family members, with a mean age at onset of 28.4 years (range, 7 to 50 years). in six of the seven, the neck was affected first. All seven developed cervical dystonia, and dysarthria or dysphonia occurred in five. Linkage data excluded the region containing the DYT1 locus, indicating that DYT1 was not responsible for ITD in this family. This study provides evidence that a gene other than DYT1 is responsible for some cases of adult cervical-onset dystonia. C1 MASSACHUSETTS GEN HOSP,CTR NEUROSCI,MOLEC NEUROGENET UNIT,E CHARLESTOWN,MA. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT HUMAN GENET,NEW HAVEN,CT 06510. OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. RP BRESSMAN, SB (reprint author), COLUMBIA PRESBYTERIAN MED CTR,INST NEUROL,DEPT NEUROL,710 W 168TH ST,NEW YORK,NY 10032, USA. RI Burke, Robert/B-7226-2011 OI Burke, Robert/0000-0002-4760-8553 FU NINDS NIH HHS [NS26656, NS26836, NS28384] NR 29 TC 62 Z9 63 U1 0 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1994 VL 44 IS 2 BP 283 EP 287 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA MW890 UT WOS:A1994MW89000018 PM 8309575 ER PT J AU SHEVELL, MI EVANS, BK AF SHEVELL, MI EVANS, BK TI THE SCHALTENBRAND EXPERIMENT, WURZBURG, 1940 - SCIENTIFIC, HISTORICAL, AND ETHICAL PERSPECTIVES SO NEUROLOGY LA English DT Article C1 UNIV ALABAMA,SCH MED,DEPT NEUROL,BIRMINGHAM,AL. MCGILL UNIV,MONTREAL CHILDRENS HOSP,DEPT PEDIAT,DIV PEDIAT NEUROL,MONTREAL,PQ,CANADA. BIRMINGHAM VA MED CTR,NEUROL SERV,BIRMINGHAM,AL. RP SHEVELL, MI (reprint author), MCGILL UNIV,MONTREAL CHILDRENS HOSP,DEPT NEUROL NEUROSURG,DIV PEDIAT NEUROL,A-514,MONTREAL H3H 1P3,PQ,CANADA. NR 43 TC 18 Z9 18 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB PY 1994 VL 44 IS 2 BP 350 EP 356 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA MW890 UT WOS:A1994MW89000035 PM 8309591 ER PT J AU AMIN, F SEEMAN, TE MOHS, RC DAVIDSON, M KNOTT, P BERKMAN, LF ALBERT, M BLAZER, D AF AMIN, F SEEMAN, TE MOHS, RC DAVIDSON, M KNOTT, P BERKMAN, LF ALBERT, M BLAZER, D TI PLASMA HOMOVANILLIC-ACID AND PERFORMANCE ON MOTOR AND COGNITIVE TASKS IN COMMUNITY-DWELLING ELDERLY - MACARTHUR STUDIES OF SUCCESSFUL AGING SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE DOPAMINE; HOMOVANILLIC ACID; BRADYKINESIA; AGING; PLASMA; STRIATUM; BRAIN ID EARLY PARKINSONS-DISEASE; MOVEMENT TIME; AGE; SELEGILINE; DOPAMINE; DEPRENYL; RAT AB To investigate the dopaminergic correlates of the aging-related motor and cognitive deficits, the dopamine metabolite homovanillic acid (HVA) in plasma was studied in a community-dwelling elderly cohort (n = 141). The results showed that hand-signature time (HST), a measure of bradykinesia, correlated negatively with plasma HVA (r = -0.24, p <.007). Similarities task performance showed a trend-level positive correlation with plasma HVA (r = 0.15, p = .08). Because plasma HVA is derived from several sources including central dopaminergic neurons and both central and peripheral noradrenergic neurons, the noradrenergic metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in plasma was also measured to indirectly estimate the relationships, with HVA originating from noradrenergic metabolism. Plasma MHPG significantly correlated with similarities scores (r = 0.34, p <.001) but not with HST. The results suggested that the association of HVA with prolonged HST may be related to central dopamine metabolism, but its association with similarities scores may be due to noradrenergic metabolism. The results raise the possibility that prolonged HST may be an indicator of preclinical brain dopamine loss in the elderly. C1 YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. RP AMIN, F (reprint author), VET ADM MED CTR,MT SINAI SCH MED,DEPT PSYCHIAT,PSYHIAT SERV 116A,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. NR 27 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 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 1994 VL 10 IS 1 BP 29 EP 35 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA MY494 UT WOS:A1994MY49400005 PM 8179792 ER PT J AU EDELHOFF, S AYER, DE ZERVOS, AS STEINGRIMSSON, E JENKINS, NA COPELAND, NG EISENMAN, RN BRENT, R DISTECHE, CM AF EDELHOFF, S AYER, DE ZERVOS, AS STEINGRIMSSON, E JENKINS, NA COPELAND, NG EISENMAN, RN BRENT, R DISTECHE, CM TI MAPPING OF 2 GENES ENCODING MEMBERS OF A DISTINCT SUBFAMILY OF MAX INTERACTING PROTEINS - MAD TO HUMAN-CHROMOSOME-2 AND MOUSE CHROMOSOME-6, AND MXI1 TO HUMAN-CHROMOSOME-10 AND MOUSE CHROMOSOME-19 SO ONCOGENE LA English DT Note ID INSITU HYBRIDIZATION; DNA-SEQUENCES; LEUKEMIA; MYC; BINDING AB Both the MAD and the MXI1 genes encode basic-helix-loop-helix-leucine zipper (bHLH-Zip) transcription factors which bind Max in vitro, forming a sequence-specific DNA-binding complex similar to the Myc-Max heterodimer. Mad and Myc compete for binding to Max. In addition, Mad has been shown to act as a transcriptional repressor while Myc appears to function as an activator. Mxi1 also appears to lack a transcriptional activation domain. Therefore, Mxi1 and Mad might antagonize Myc function and are candidate tumor suppressor genes. We report here the mapping of the MAD and MXI1 genes in human and mouse by fluorescence in situ hybridization (FISH) and by recombination mapping. The MAD gene was mapped to human chromosome 2 at band p13 by FISH and to mouse chromosome 6 by meiotic mapping. The MXI1 gene was mapped to human chromosome 10 at band q25 and on mouse chromosome 19 at region D by FISH. There was a second site of hybridization on mouse chromosome 2 at region C, which may represent a pseudogene or a related sequence. The mapping results confirm regions of conservation between human chromosome 2p13 and mouse chromosome 6 and between chromosome 10q25 and mouse chromosome 19D. Human chromosomes 2p13 and 10q25 have been involved in specific tumors where the role of Mad and Mxi1 can now he investigated. C1 UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 26 TC 111 Z9 111 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB PY 1994 VL 9 IS 2 BP 665 EP 668 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA MW248 UT WOS:A1994MW24800036 PM 8290278 ER PT J AU RUBIN, PAD BILYK, JR SHORE, JW SUTULA, FC CHENG, HM AF RUBIN, PAD BILYK, JR SHORE, JW SUTULA, FC CHENG, HM TI MAGNETIC-RESONANCE-IMAGING OF THE LACRIMAL DRAINAGE SYSTEM SO OPHTHALMOLOGY LA English DT Article ID MR AB Background: Magnetic resonance imaging (MRI) has excellent spatial and soft tissue resolution in the periocular and orbital region, especially when combined with surface coil techniques. Other methods, including computed tomography, dacryocystography, and dacryoscintigraphy provide limited information in the area of the lacrimal drainage system. Magnetic resonance imaging was used in conjunction with other imaging modalities to compare the anatomic detail and clinically relevant information obtained about various pathologic processes in the lacrimal drainage area. Methods: Patients with a variety of lacrimal drainage disorders underwent MRI with either head or surface coils. Contrast agents also were used in selected cases. Seven case reports are presented. Results: Magnetic resonance imaging provided detailed information about local anatomy, extent of pathology, and, in some cases, etiology of the pathology. Conclusions: Magnetic resonance imaging with surface coils provides detailed soft tissue information when compared with dacryocystography and computed tomography in the area of the lacrimal drainage system. In selected cases of lacrimal drainage system pathology, MRI may provide data that affect patient management. RP RUBIN, PAD (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114, USA. NR 12 TC 37 Z9 38 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1994 VL 101 IS 2 BP 235 EP 243 PG 9 WC Ophthalmology SC Ophthalmology GA MX333 UT WOS:A1994MX33300012 PM 8115144 ER PT J AU DELAMAZA, MS JABBUR, NS FOSTER, CS AF DELAMAZA, MS JABBUR, NS FOSTER, CS TI SEVERITY OF SCLERITIS AND EPISCLERITIS SO OPHTHALMOLOGY LA English DT Article ID POSTERIOR SCLERITIS; DISEASE AB Purpose: inflammation of the wall of the eyeball may extend to adjacent ocular tissues with blinding consequences and may be associated with potentially lethal systemic disorders. This study was undertaken to evaluate the ocular complications and systemic disease associations of the different types of scleritis and episcleritis. Methods: Ocular complications and specific disease association were evaluated in 266 patients (358 eyes) with different types of scleritis (diffuse, nodular, necrotizing, scleromalacia perforans, and posterior) and episcleritis (simple and nodular). Results: In patients with scleritis, decrease in vision occurred in 37%, anterior uveitis was present in 42%, peripheral ulcerative keratitis developed in 14%, glaucoma occurred in 13%, cataract formed in 17%, fundus abnormalities appeared in 6%, and specific disease association was uncovered in 57%. These findings were most commonly associated with necrotizing scleritis. In patients with episcleritis, decreased vision occurred in 2%, anterior uveitis was present in 11%, glaucoma developed in 4%, cataract formed in 2%, and specific disease association was uncovered in 32%. These findings were similar in simple and nodular episcleritis. Conclusions: In a patient with scleritis, examination of visual acuity, anterior uvea, cornea, lens, intraocular pressure, and fundus must be performed in every follow-up visit, and a meticulous approach for detection of a specific associated disease must be undertaken since the first visit. Scleritis is more severe than episcleritis, and necrotizing scleritis is the most severe type of scleritis. Classification of scleritis and episcleritis provides valuable prognostic information. C1 HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM,SCH MED, IMMUNOL SERV,HILLES IMMUNOL LAB, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, OCULAR IMMUNOL SERV, BOSTON, MA 02114 USA. NR 13 TC 92 Z9 94 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD FEB PY 1994 VL 101 IS 2 BP 389 EP 396 PG 8 WC Ophthalmology SC Ophthalmology GA MX333 UT WOS:A1994MX33300030 PM 8115160 ER PT J AU DAVIES, JP HARRIS, WH AF DAVIES, JP HARRIS, WH TI TENSILE BONDING STRENGTH OF THE CEMENT-PROSTHESIS INTERFACE SO ORTHOPEDICS LA English DT Article AB A widely held belief among orthopedic surgeons is that there is no adhesion between polymethylmethacrylate bone cement and metal. However, a bond does form between the cement and the standard grit-blasted implant finish. Moreover, it has been shown that disruption of this bond or ''debonding'' of this interface is a major factor in the initiation of failure of some cemented total joint arthroplasties. It is the purpose of this study to determine the tensile pull-off strength of the bone cement-implant surface interface. A 1.27 cm (0.5 in) layer of Simplex-P bone cement was cured between two Co-Cr-Mo pins of 2.22 cm (0.875 in) diameter which had the standard implant finish on the surface that was interfaced with the cement. The specimens were tested in an MTS machine in stroke control with a cross head rate of 1 in per minute. The maximum load to failure was recorded. Bonding of the cement to the surface does occur. The tensile pull-off strength of the bone cement-implant surface interface is approximately 5 MPa. Other studies have shown that maintaining this bond between the stem and cement is important in maintaining the stability of cemented total joint arthroplasties. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. NR 0 TC 26 Z9 26 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD FEB PY 1994 VL 17 IS 2 BP 171 EP 173 PG 3 WC Orthopedics SC Orthopedics GA MW202 UT WOS:A1994MW20200010 PM 8190680 ER PT J AU VACANTI, CA VACANTI, JP AF VACANTI, CA VACANTI, JP TI BONE AND CARTILAGE RECONSTRUCTION WITH TISSUE ENGINEERING APPROACHES SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID TRANSPLANTATION; HEPATOCYTES; CELLS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. RP VACANTI, CA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,WHITE 5,32 FRUIT ST,BOSTON,MA 02114, USA. NR 27 TC 123 Z9 140 U1 3 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD FEB PY 1994 VL 27 IS 1 BP 263 EP 276 PG 14 WC Otorhinolaryngology SC Otorhinolaryngology GA MX758 UT WOS:A1994MX75800017 PM 8159426 ER PT J AU MULLENIX, PJ KERNAN, WJ SCHUNIOR, A HOWES, A WABER, DP SALLAN, SE TARBELL, NJ AF MULLENIX, PJ KERNAN, WJ SCHUNIOR, A HOWES, A WABER, DP SALLAN, SE TARBELL, NJ TI INTERACTIONS OF STEROID, METHOTREXATE, AND RADIATION DETERMINE NEUROTOXICITY IN AN ANIMAL-MODEL TO STUDY THERAPY FOR CHILDHOOD LEUKEMIA SO PEDIATRIC RESEARCH LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CENTRAL-NERVOUS-SYSTEM; ACUTE LYMPHOCYTIC-LEUKEMIA; COMPUTER-PATTERN RECOGNITION; GROWTH-HORMONE SECRETION; CANCER STUDY-GROUP; CRANIAL IRRADIATION; BEHAVIORAL ACTS; TIME STRUCTURE; INTELLECTUAL FUNCTION AB Children with leukemia receive CNS therapy to improve long-term survival. Neurotoxic effects, such as cognitive impairment, have been associated with this therapy. A rat model was developed to determine which agent, or combination of agents, in CNS therapy causes neurotoxicity. The agents examined were cranial irradiation (1000 cGy), methotrexate (2 or 4 mg/kg, intraperitoneally), and prednisolone (18 or 36 mg/kg, intraperitoneally). Young Sprague-Dawley rats were exposed to each agent alone or to two- or three-agent combinations. Each therapy had matched controls that received sham radiation and/or intraperitoneal saline. Subsequent to exposure, spontaneous behavior was tested using a computer pattern recognition system, which recorded and classified behavior in a novel environment. Behavioral initiations, total times, and time structures were compared in therapy and control groups. Combined rather than single-agent therapies had more behavioral effects, and these were dose- and sex-dependent. Synergistic interactions between agents caused behavioral deficits, and components of the combination determined the abnormality. Some combinations interacted antagonistically, and thus mitigated behavioral deficits. Prednisolone was clearly pivotal to behavioral outcome. A low prednisolone dose antagonized methotrexate preventing deficits, whereas a higher prednisolone dose altered behavior by enhancing effects of methotrexate and radiation. These findings emphasize that steroids are important in agent interactions. Their role in morbidity associated with leukemia treatment protocols may be equally important as that of methotrexate and cranial irradiation. C1 HARVARD UNIV, SCH MED, JOINT CTR RADIAT THERAPY, DEPT RADIAT ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02115 USA. DANA FARBER CANC INST, DEPT PEDIAT ONCOL, BOSTON, MA 02115 USA. IOWA STATE UNIV SCI & TECHNOL, COLL VET MED, VET DIAGNOST LAB, AMES, IA 50011 USA. RP FORSYTH RES INST, DEPT TOXICOL, 140 FENWAY, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA53858] NR 48 TC 28 Z9 28 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD FEB PY 1994 VL 35 IS 2 BP 171 EP 178 DI 10.1203/00006450-199402000-00009 PG 8 WC Pediatrics SC Pediatrics GA MU439 UT WOS:A1994MU43900008 PM 8165051 ER PT J AU SMITH, G MCGIMPSEY, WG LYNCH, MC KOCHEVAR, IE REDMOND, RW AF SMITH, G MCGIMPSEY, WG LYNCH, MC KOCHEVAR, IE REDMOND, RW TI AN EFFICIENT OXYGEN INDEPENDENT 2-PHOTON PHOTOSENSITIZATION MECHANISM SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Note ID BENGAL AB A novel oxygen-independent photosensitization mechanism from the upper triplet state (T-n) of rose bengal has been demonstrated by selectively populating T-n by sequential two-color laser excitation. Products formed from T-n inhibit red blood cell acetylcholinesterase and decrease viability of P388D(1) mouse macrophage monocyte cells as measured by trypan blue exclusion assay. Laser flash photolysis studies indicate that T-n reacts efficiently, as evidenced by permanent photobleaching of T-1 absorption, with chemical yields approaching unit efficiency. This mechanism may have application for oxygen deficient photosensitization under high intensity, pulsed laser irradiation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. WORCESTER POLYTECH INST,DEPT CHEM,WORCESTER,MA 01609. FU NIGMS NIH HHS [GM30755] NR 10 TC 32 Z9 34 U1 0 U2 0 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 FEB PY 1994 VL 59 IS 2 BP 135 EP 139 DI 10.1111/j.1751-1097.1994.tb05012.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MZ674 UT WOS:A1994MZ67400001 PM 8165232 ER PT J AU GILLBODY, KM KREBS, DE PARKER, SW RILEY, PO AF GILLBODY, KM KREBS, DE PARKER, SW RILEY, PO TI PHYSICAL THERAPY MANAGEMENT OF PERIPHERAL VESTIBULAR DYSFUNCTION - 2 CLINICAL CASE-REPORTS SO PHYSICAL THERAPY LA English DT Note DE BALANCE; BALANCE REHABILITATION; POSTURAL CONTROL; VESTIBULAR REHABILITATION ID REHABILITATION; DIZZINESS; BALANCE; REFLEX AB We describe the treatment of two patients with peripheral vestibular dysfunction using a novel, staged exercise program. Response to treatment was documented The first patient, a 62-year-old woman with unilateral vestibular dysfunction (UVD) and a 6-month history of disequilibrium following herpes zoster oticus resulting in damage to the right inner ear, was treated with an 8-week course of vestibular physical therapy. During the 8 weeks, the patient attended weekly physical therapy sessions and was trained to perform vestibular adaptation exercises on a daily basis at home. The second patient, a 53-year-old woman with progressive disequilibrium secondary to profound bilateral vestibular hypofunction (BVH), was treated with a 16-week course of vestibular physical therapy. During the first 8 weeks, the patient attended weekly physical therapy sessions and was trained to perform vestibular adaptation and substitution exercises on a daily basis at home. During the second 8 weeks, the patient continued performing vestibular physical therapy exercises at home independently. Vestibular function (sinusoidal vertical axis rotation testing), postural control (clinical tests and posturography), stability during the performance of selected activities of daily living (ADLs), and self-perception of symptoms and handicap were measured prior to and at the conclusion of treatment for both patients and at the midpoint of treatment for the patient with BVH. After 8 weeks of treatment, both patients reported improvements in self-perception of symptoms and handicap and demonstrated objective improvements in clinical balance tests, posturography, and several kinematic indicators of stability during the performance of selected ADLs Further improvements were noted in the patient with BVH after 16 weeks of treatment Improvements in postural control were noted after 8 weeks of treatment for the patient with UVD and after 16 weeks for the patient with BVH. Vestibular function improved during the course of treatment for the patient with UVD only. These case reports describe two different individualized treatment programs and document self-reported and laboratory-measured functional improvements in two patients with vestibular deficients-one with unilateral damage and one with bilateral damage. C1 MGH INST HLTH PROFESS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BIOMOT LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02138. MIT,CAMBRIDGE,MA 02139. RP GILLBODY, KM (reprint author), MASSACHUSETTS GEN HOSP,PHYS THERAPY SERV,FRUIT ST,BOSTON,MA 02114, USA. RI Riley, Patrick/B-3053-2009 NR 24 TC 27 Z9 30 U1 0 U2 0 PU AMER PHYS THER ASSN PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD FEB PY 1994 VL 74 IS 2 BP 129 EP 142 PG 14 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA MU935 UT WOS:A1994MU93500011 PM 8290618 ER PT J AU KAHN, RS TRESTMAN, R LAWLOR, BA GABRIEL, S DAVIDSON, M SIEVER, L AF KAHN, RS TRESTMAN, R LAWLOR, BA GABRIEL, S DAVIDSON, M SIEVER, L TI EFFECTS OF IPSAPIRONE IN HEALTHY-SUBJECTS - A DOSE-RESPONSE STUDY SO PSYCHOPHARMACOLOGY LA English DT Article DE IPSAPIRONE; DOSE-RESPONSE; SEROTONIN ID OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN RECEPTOR HYPERSENSITIVITY; PITUITARY-ADRENAL AXIS; PANIC DISORDER; META-CHLOROPHENYLPIPERAZINE; NEURO-ENDOCRINE; 5-HT1A RECEPTORS; HUMANS; ACTIVATION; PROLACTIN AB A dose-response study of ipsapirone (IFS), a 5HT(1a) partial agonist, was conducted in healthy male subjects. IPS was administered in doses of 5,10 and 20 mg PO in a placebo-controlled, double-blind design to 15 subjects on 4 test days separated by at least 3 days. Oral temperature, ACTH, cortisol, prolactin, blood pressure, pulse rate and behavioral variables were assessed every 30 min for 3 h after administration of tablets (at 10:00 A.M.). IPS at 20 mg significantly decreased temperature and increased cortisol levels. Although IPS increased ACTH levels at 20 mg, this effect was variable and not significant. IPS did not affect prolactin levels nor did it have any behavioral effects. Although 20 mg IPS decreased blood pressure and pulse rate in one subject, overall it had no significant effect on these parameters. IPS at 20 mg PO appears a useful probe to test 5HT(1a) function when temperature and cortisol are used as response variables. These results replicate earlier studies on the effect of IPS in healthy human subjects. C1 ST JAMES HOSP,DEPT PSYCHIAT,DUBLIN 8,IRELAND. RP KAHN, RS (reprint author), BRONX VET AFFAIRS MED CTR,MT SINAI SCH MED,DEPT PSYCHIAT,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. NR 51 TC 29 Z9 29 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD FEB PY 1994 VL 114 IS 1 BP 155 EP 160 DI 10.1007/BF02245457 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA MW866 UT WOS:A1994MW86600020 PM 7846198 ER PT J AU SCHWARTZ, CE COLE, BF GELBER, RD AF SCHWARTZ, CE COLE, BF GELBER, RD TI MEASURING PATIENT-CENTERED OUTCOMES - ADAPTING THE Q-TWIST FOR MULTIPLE-SCLEROSIS SO QUALITY OF LIFE RESEARCH LA English DT Meeting Abstract C1 ROCKY MT MS CTR,ENGLEWOOD,CO. DANA FARBER CANC INST,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SCHWARTZ, CE (reprint author), FROMTIER SCI & TECHNOL RES FDN INC,AMHERST,MA, USA. RI Cole, Bernard/I-3775-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD FEB PY 1994 VL 3 IS 1 BP 62 EP 62 PG 1 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA MW605 UT WOS:A1994MW60500049 ER PT J AU ORTIZBRAVO, E BAKER, DG SCHUMACHER, HR AF ORTIZBRAVO, E BAKER, DG SCHUMACHER, HR TI MECHANISMS INVOLVED IN THE INITIATION, PERPETUATION AND SELF-LIMITED NATURE OF ACUTE GOUTY-ARTHRITIS SO REVUE DU RHUMATISME LA French DT Article DE GOUT ID MONOSODIUM URATE CRYSTALS; CALCIUM PYROPHOSPHATE DIHYDRATE; MICROCRYSTALLINE SODIUM URATE; INDUCED INFLAMMATION; HUMAN-NEUTROPHILS; SYNOVIAL FIBROBLAST; PROTEIN ADSORPTION; SERUM-PROTEINS; MESSENGER-RNA; CELLS C1 HOP UNIV PENN,SERV RHUMATOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,CTR RHUMATOL & IMMUNOL,PHILADELPHIA,PA 19104. NR 73 TC 0 Z9 0 U1 0 U2 1 PU EXPANSION SCI FRANCAISE PI PARIS PA 31 BLVD LATOUR MAUBOURG, 75007 PARIS, FRANCE SN 1169-8446 J9 REV RHUM JI Rev. Rhum. PD FEB PY 1994 VL 61 IS 2 BP 132 EP 138 PG 7 WC Rheumatology SC Rheumatology GA MY832 UT WOS:A1994MY83200009 PM 7920501 ER PT J AU BREAKEFIELD, XO AF BREAKEFIELD, XO TI OVERDUE CREDIT SO SCIENTIFIC AMERICAN LA English DT Letter RP BREAKEFIELD, XO (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD FEB PY 1994 VL 270 IS 2 BP 10 EP 10 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR680 UT WOS:A1994MR68000005 ER PT J AU SCULLY, SP TEMPLE, HT OKEEFE, RJ GEBHARDT, MC AF SCULLY, SP TEMPLE, HT OKEEFE, RJ GEBHARDT, MC TI CASE-REPORT-830 - ANEURYSMAL BONE-CYST SO SKELETAL RADIOLOGY LA English DT Note RP SCULLY, SP (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114, USA. NR 22 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD FEB PY 1994 VL 23 IS 2 BP 157 EP 160 PG 4 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA MY456 UT WOS:A1994MY45600017 PM 8191304 ER PT J AU MORIKAWA, E MOSKOWITZ, MA HUANG, ZH YOSHIDA, T IRIKURA, K DALKARA, T AF MORIKAWA, E MOSKOWITZ, MA HUANG, ZH YOSHIDA, T IRIKURA, K DALKARA, T TI L-ARGININE INFUSION PROMOTES NITRIC OXIDE-DEPENDENT VASODILATION, INCREASES REGIONAL CEREBRAL BLOOD-FLOW, AND REDUCES INFARCTION VOLUME IN THE RAT SO STROKE LA English DT Article DE AMINO ACIDS; CEREBRAL BLOOD FLOW; CEREBRAL ISCHEMIA, FOCAL; NITRIC OXIDE; RATS ID CRANIAL WINDOW TECHNIQUE; ENDOTHELIAL-CELLS; DETAILED DESCRIPTION; ARTERY OCCLUSION; PIAL ARTERIOLES; ISCHEMIA; INHIBITION; MODEL AB Background and Purpose We previously reported that L-arginine infusion increased pial vessel diameter by nitric oxide-dependent mechanisms, improved regional cerebral blood flow (rCBF) distal to middle cerebral artery (MCA) occlusion, and reduced infarction volume in spontaneously hypertensive rats when administered intraperitoneally before and after MCA occlusion. In this report we extend our findings (1) by examining the time course of L-arginine on rCBF and pial vessel diameter under basal conditions and on rCBF after MCA. occlusion and (2) by reproducing the protective effect of L-arginine on infarct volume when given intravenously immediately after the onset of MCA occlusion in both normotensive and hypertensive models of focal cerebral ischemia. Methods Changes in pial vessel diameter (closed cranial window) and rCBF (laser-Doppler flowmetry) were measured over time after L-arginine infusion into anesthetized Sprague-Dawley rats, rCBF was also measured distal to MCA occlusion in a brain region showing rCBF reductions in the range of 80% of baseline. The effects of infusing L-arginine (300 mg/kg for 10 minutes beginning 5 minutes after occlusion) were assessed on infarction volume in Sprague-Dawley rats after proximal MCA occlusion and in spontaneously hypertensive rats after common carotid artery plus distal MCA occlusion. Results L-Arginine (300 mg/kg IV) elevated rCBF by 20% when measured in the dorsolateral cortex of Sprague-Dawley rats and caused L-nitroarginine-methyl ester-inhibitable increases in pial vessel diameter. L-Arginine (greater than or equal to 30 mg/kg IV) increased blood flow distal to MCA occlusion by 50%. These effects were sustained throughout the observation period (70 to 105 minutes). Changes in mean arterial blood pressure were not observed. L-Arginine (300 mg/kg IV) reduced infarction volume by 35% and 28% in Sprague-Dawley and spontaneously hypertensive rats, respectively, when examined 24 hours after vessel occlusion. Conclusions These studies extend our previous findings by demonstrating that exogenous L-arginine induces sustained rCBF increases in normal brain as well as in a marginally perfused brain region distal to MCA occlusion. Our data in Sprague-Dawley rats support the conclusion that L-arginine-induced increases in rCBF can decrease infarction volume. We conclude that nitric oxide-mediated mechanisms increase rCBF and decrease infarction Volume after MCA occlusion in both normotensive and hypertensive animals. C1 MASSACHUSETTS GEN HOSP,NEUROSURG SERV,STROKE RES LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS-10828] NR 29 TC 198 Z9 206 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 1994 VL 25 IS 2 BP 429 EP 435 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA MU285 UT WOS:A1994MU28500031 PM 7508154 ER PT J AU KOROSHETZ, WJ AF KOROSHETZ, WJ TI DELAYED PROTECTION BY MK-801 AND TETRODOTOXIN IN A RAT ORGANOTYPIC HIPPOCAMPAL CULTURE MODEL OF ISCHEMIA - EDITORIAL COMMENT SO STROKE LA English DT Editorial Material RP KOROSHETZ, WJ (reprint author), MASSACHUSETTS GEN HOSP,STROKE SERV,BOSTON,MA, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 1994 VL 25 IS 2 BP 464 EP 465 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA MU285 UT WOS:A1994MU28500040 ER PT J AU SLANETZ, PJ LEE, R PAGE, R JACOBS, EE LARAIA, P VLAHAKES, GJ AF SLANETZ, PJ LEE, R PAGE, R JACOBS, EE LARAIA, P VLAHAKES, GJ TI HEMOGLOBIN BLOOD SUBSTITUTES IN EXTENDED PREOPERATIVE AUTOLOGOUS BLOOD DONATION - AN EXPERIMENTAL-STUDY SO SURGERY LA English DT Article ID ELECTIVE CARDIAC-SURGERY; PLATELET-RICH PLASMA; MYOCARDIAL REVASCULARIZATION; BOVINE HEMOGLOBIN; OXYGEN-TRANSPORT; STROMA-FREE; TRANSFUSION; SAFETY; HEMODILUTION; OPERATIONS AB Background. The risks of homologous blood transfusion have stimulated interest in developing possible alternatives. In this study we examined the efficacy of using a hemoglobin-derived blood substitute to augment and extend preoperative autologous blood donation. Methods. In an ovine model, two experimental groups (n = 6 each) of animals donated either 45% or 80% or more of calculated blood volume, which was replaced with a polymerized bovine hemoglobin solution. Two control groups (n = 6 each) either did not donate or donated 45% of calculated blood volume, which was replaced with a 6% hetastarch solution. Twenty-four hours after blood donation, sheep underwent a measured surgical stress with standardized intraoperative blood loss; donated blood was reinfused. Results. Extended autologous blood donation and replacement with this blood substitute were efficacious in supporting oxygen consumption; there was no systemic toxicity. After the postoperative replacement of autologous blood, animals that donated 80% or more of red cell mass exhibited overall blood conservation with a final hematocrit of 25.7% +/- 3.6%, compared with 20.5% +/- 2.0% (p < 0.05) and with 21.5% +/- 1.1% (p < 0.05) in both control groups. Conclusions. This study suggests that the benefits of a blood substitute can be combined with autologous blood donation to (1) safely increase the amount of autologous blood donated while supporting oxygen consumption, (2) avoid the need for advanced preoperative donation, and (3) decrease the need for homologous blood transfusion. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,CADIAC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. OI Slanetz, Priscilla/0000-0003-1248-5116 NR 34 TC 37 Z9 37 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 1994 VL 115 IS 2 BP 246 EP 254 PG 9 WC Surgery SC Surgery GA MV728 UT WOS:A1994MV72800016 PM 8310414 ER PT J AU HOLMES, LB HARVEY, EA AF HOLMES, LB HARVEY, EA TI HOLOPROSENCEPHALY AND THE TERATOGENICITY OF ANTICONVULSANTS SO TERATOLOGY LA English DT Letter RP HOLMES, LB (reprint author), MASSACHUSETTS GEN HOSP,GENET & TERATOL UNIT,BOSTON,MA 02114, USA. NR 3 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD FEB PY 1994 VL 49 IS 2 BP 82 EP 82 DI 10.1002/tera.1420490203 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA MZ112 UT WOS:A1994MZ11200002 PM 8016748 ER PT J AU ORAK, JK SINGH, AK RAJAGOPALAN, PR SINGH, I AF ORAK, JK SINGH, AK RAJAGOPALAN, PR SINGH, I TI MORPHOLOGICAL ANALYSIS OF MITOCHONDRIAL INTEGRITY IN PROLONGED COLD RENAL ISCHEMIA UTILIZING EURO-COLLINS VERSUS UNIVERSITY-OF-WISCONSIN PRESERVATION SOLUTION IN A WHOLE ORGAN MODEL SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st International Congress on Pediatric Transplantation CY AUG 29-SEP 01, 1993 CL MINNEAPOLIS, MN ID KIDNEY-PRESERVATION; UW SOLUTION; OF-WISCONSIN; SUPEROXIDE-DISMUTASE; RAT-KIDNEY; TRANSPLANTATION; STORAGE; PEROXISOMES; INJURY C1 RALPH JOHNSON VA HOSP,CHARLESTON,SC. RP ORAK, JK (reprint author), MED UNIV S CAROLINA,DIV PEDIAT NEPHROL,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 26 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD FEB PY 1994 VL 26 IS 1 BP 122 EP 125 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA MW599 UT WOS:A1994MW59900062 PM 8108903 ER PT J AU NAKAI, K TRAYNOR, FF ISOBE, M AF NAKAI, K TRAYNOR, FF ISOBE, M TI TIME-COURSE AND LOCALIZATION OF INTERCELLULAR-ADHESION MOLECULE-1 INDUCTION IN KIDNEY ALLOGRAFTS IN MICE SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID TUMOR NECROSIS FACTOR; MONOCLONAL-ANTIBODY; IMMUNE-SYSTEM; INTERFERON-GAMMA; RENAL-ALLOGRAFTS; ICAM-1; EXPRESSION; REJECTION; ACTIVATION; ANTIGENS C1 IWATE MED UNIV,DEPT CLIN PATHOL,MORIOKA,IWATE 020,JAPAN. UNIV TOKYO,DEPT INTERNAL MED 3,TOKYO,JAPAN. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA. NR 29 TC 13 Z9 14 U1 0 U2 1 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 FEB PY 1994 VL 26 IS 1 BP 349 EP 353 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA MW599 UT WOS:A1994MW59900163 PM 7906445 ER PT J AU BURGLIN, TR AF BURGLIN, TR TI A CAENORHABDITIS-ELEGANS PROSPERO HOMOLOG DEFINES A NOVEL DOMAIN SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter ID DROSOPHILA RP BURGLIN, TR (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT GENET,DEPT MOLEC BIOL,WELLMAN 8,BOSTON,MA 02114, USA. NR 8 TC 31 Z9 32 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD FEB PY 1994 VL 19 IS 2 BP 70 EP 71 DI 10.1016/0968-0004(94)90035-3 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MW616 UT WOS:A1994MW61600006 PM 7909177 ER PT J AU DAIBATA, M SPECK, SH MULDER, C SAIRENJI, T AF DAIBATA, M SPECK, SH MULDER, C SAIRENJI, T TI REGULATION OF THE BZLF1 PROMOTER OF EPSTEIN-BARR-VIRUS BY 2ND MESSENGERS IN ANTI-IMMUNOGLOBULIN-TREATED B-CELLS SO VIROLOGY LA English DT Article ID PROTEIN-KINASE-C; SWITCH GENE BZLF1; TYROSINE PHOSPHORYLATION; LYMPHOCYTES-B; TRANSCRIPTION FACTOR; SIGNAL TRANSDUCTION; TRANS ACTIVATION; PRODUCTIVE CYCLE; PHOSPHOLIPASE-C; LATENT EBV C1 UNIV MASSACHUSETTS,SCH MED,DEPT MOLEC GENET & MICROBIOL,WORCESTER,MA 01655. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02215. RP DAIBATA, M (reprint author), UNIV MASSACHUSETTS,SCH MED,DEPT PHARMACOL,WORCESTER,MA 01655, USA. FU NCI NIH HHS [CA-54789]; NIAID NIH HHS [AI-23061] NR 44 TC 52 Z9 53 U1 5 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 1 PY 1994 VL 198 IS 2 BP 446 EP 454 DI 10.1006/viro.1994.1056 PG 9 WC Virology SC Virology GA MV841 UT WOS:A1994MV84100004 PM 8291228 ER PT J AU TOLENTINO, MJ MILLER, S GAUDIO, AR SANDBERG, MA AF TOLENTINO, MJ MILLER, S GAUDIO, AR SANDBERG, MA TI VISUAL-FIELD DEFICITS IN EARLY AGE-RELATED MACULAR DEGENERATION SO VISION RESEARCH LA English DT Article DE MACULAR DEGENERATION; VISUAL FIELD; ATROPHY; DRUSEN; METAMORPHOPSIA ID FELLOW EYE AB Patients with early age-related macular degeneration (AMD) may retain good visual acuity but experience distortion and other qualitative visual changes. The purpose of the present study was to determine whether deficits of form recognition, as well as of light sensitivity; were related to retinal pigment epithelial (RPE) atrophy and/or drusen. We assessed form recognition deficits by the Amsler grid and by a perimetric test of letter recognition and sensitivity deficits by the macular threshold test of the Humphrey Field Analyzer in 59 patients with AMD and visual acuities of 20/40 or better. The number of defects on each test was compared with the area of RPE atrophy and with the area of drusen determined from fundus photographs. Multiple regression analyses based on ordinal data revealed that the number of visual field defects by each test was significantly correlated with the area of atrophy, but not with the area of drusen. There was also no significant tendency for a patient with a regional preponderance of drusen to have more impairment in the corresponding visual field. These results suggest that deficits of form recognition, as well as of sensitivity, in patients with early stages of AMD can be attributed to alteration of photoreceptor function associated with RPE atrophy, but not with drusen. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. FU NEI NIH HHS [NEI EY08398] NR 11 TC 34 Z9 34 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0042-6989 J9 VISION RES JI Vision Res. PD FEB PY 1994 VL 34 IS 3 BP 409 EP 413 DI 10.1016/0042-6989(94)90099-X PG 5 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA MP728 UT WOS:A1994MP72800013 PM 8160376 ER PT J AU TORCHILIN, VP AF TORCHILIN, VP TI CHELATING POLYMER-BASED IMMUNOCONJUGATES - NEW AGENTS FOR DIAGNOSTIC-IMAGING SO VYSOKOMOLEKULYARNYE SOEDINENIYA SERIYA A & SERIYA B LA Russian DT Article ID MONOCLONAL-ANTIBODIES; RADIOIMMUNOTHERAPY AB New family of polymers is synthesized for labeling proteins (antibodies) with multiple heavy metal ions for the use in gamma- and MR-imaging. Polylysine of different molecular weight was used in the majority of experiments, modified with multiple chelating moeities such as diethylenetriamine pentaacetic acid. The modification permits to introduce in a single polymer molecule (M(W) = 55 kDa) up to 100 chelating units able to firmly bind metals such as In, Gd, Mn, Tc, Re and others, which are widely used in radioscintigraphy and NMR-tomography. To make polymeric chelates specific towards target areas, they were conjugated with monoclonal antibodies. Special technique of antibody modification with chelating polymers was developed, permitting to bind whole antibody or its Fab fragment with the polymer via minimal number of covalent bonds and with minimal loss in immunoreactivity. In vitro studies with radiometals demonstrated extremely high labeling efficacy of antibody: in case of In-111 the specific radioactivity achieved was up to 100 mCi per mg protein in comparison with 3 to 5 mCi per mg as obtained using traditional labeling protocols. In vivo studies in rabbits with experimental myocardial infarction and in mice with implanted human breast tumor demonstrated fast and quantitative label accumulation in target areas. Amphiphilic derivatives of chelating polymers have been synthesized able to incorporate into phospholipid membranes. Liposomes with surface-incorporated Gd-loaded chelating polymers have been successfully used for MR-imaging of lymph nodes in rabbits. C1 HARVARD UNIV,CAMBRIDGE,MA 02138. RP TORCHILIN, VP (reprint author), MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,149 13TH ST,BOSTON,MA 02129, USA. NR 20 TC 1 Z9 1 U1 0 U2 1 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0507-5475 J9 VYSOKOMOL SOEDIN JI Vysokomol. Soedin. PD FEB PY 1994 VL 36 IS 2 BP 279 EP 297 PG 19 WC Polymer Science SC Polymer Science GA ND444 UT WOS:A1994ND44400014 ER PT J AU DREYER, EB PAN, ZH STORM, S LIPTON, SA AF DREYER, EB PAN, ZH STORM, S LIPTON, SA TI GREATER SENSITIVITY OF LARGER RETINAL GANGLION-CELLS TO NMDA-MEDIATED CELL DEATH SO NEUROREPORT LA English DT Article DE N-METHYL-D-ASPARTATE; RETINAL GANGLION CELLS; NEURONS; EXCITOTOXICITY; GLUTAMATE; CELL SIZE; CELL DEATH ID AMYOTROPHIC-LATERAL-SCLEROSIS; OPTIC-NERVE DAMAGE; RAT RETINA; NEUROTOXICITY; GLUTAMATE; RECEPTOR; MK-801; DISEASE; CULTURE; INJURY AB GLUTAMATE toxicity in retinal ganglion cells has well documented both in vitro and in vivo, and has been suggested to play a role in the neuronal loss in glaucoma. Of note, glaucoma selectively damages larger retinal ganglion cells first, and we therefore sought to explore whether glutamate-mediated cell death was likewise more pronounced in larger retinal ganglion cells. We now report that glutamate-which exerts its toxic effect on neurons predominantly through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor-is more toxic to larger retinal ganglion cells both in tissue culture and in the intact rat eye. Cells smaller than 10 mu m were relatively unaffected by glutamate or NMDA. These agents are, however, markedly toxic to retinal ganglion cells larger than 10 mu m. These observations indicate that glutamate-mediated loss is seen first in larger retinal ganglion cells, in a similar fashion to the pattern of loss seen in glaucoma. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. BETH ISRAEL HOSP,BRIGHAM & WOMENS HOSP,DEPT NEUROL,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. RP DREYER, EB (reprint author), CHILDRENS HOSP MED CTR,DEPT NEUROL,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NEI NIH HHS [R01 EY05477]; NINDS NIH HHS [K08 NS01395] NR 24 TC 87 Z9 91 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JAN 31 PY 1994 VL 5 IS 5 BP 629 EP 631 DI 10.1097/00001756-199401000-00024 PG 3 WC Neurosciences SC Neurosciences & Neurology GA NA357 UT WOS:A1994NA35700024 PM 7912962 ER PT J AU LIPSITZ, SR BUONCRISTIANI, JF AF LIPSITZ, SR BUONCRISTIANI, JF TI A ROBUST GOODNESS-OF-FIT TEST STATISTIC WITH APPLICATION TO ORDINAL REGRESSION-MODELS SO STATISTICS IN MEDICINE LA English DT Article ID COVARIANCE AB We propose a goodness-of-fit test statistic for linear regression with heterogeneous variance, which is asymptotically chi-square if the given model is correct. The test statistic is computed as a quadratic form of observed minus predicted responses. We apply the method to a linear regression for an ordinal categorical response, the wheezing status of a child (no wheeze, wheeze with cold, wheeze apart from cold) as a function of maternal smoking and city of residence. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. WHEATON COLL,NORTON,MA 02766. RP LIPSITZ, SR (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 55576]; NIAID NIH HHS [AI 24643]; NIGMS NIH HHS [GM 29745] NR 11 TC 3 Z9 3 U1 1 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 JAN 30 PY 1994 VL 13 IS 2 BP 143 EP 152 DI 10.1002/sim.4780130205 PG 10 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 MR193 UT WOS:A1994MR19300004 PM 8122050 ER PT J AU HARRIS, N PETERS, LL EICHER, EM RITS, M RASPBERRY, D EICHBAUM, QG SUPER, M EZEKOWITZ, RAB AF HARRIS, N PETERS, LL EICHER, EM RITS, M RASPBERRY, D EICHBAUM, QG SUPER, M EZEKOWITZ, RAB TI THE EXON-INTRON STRUCTURE AND CHROMOSOMAL LOCALIZATION OF THE MOUSE MACROPHAGE MANNOSE RECEPTOR GENE MRCL - IDENTIFICATION OF A RICIN-LIKE DOMAIN AT THE N-TERMINUS OF THE RECEPTOR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CARBOHYDRATE-RECOGNITION DOMAINS; LEUKOCYTE ADHESION MOLECULE-1; LIVER ASIALOGLYCOPROTEIN RECEPTOR; BINDING PROTEIN GENE; AMINO-ACID SEQUENCE; RAT KUPFFER CELLS; EVOLUTIONARY RELATIONSHIP; COMMUNIS AGGLUTININ; LECTIN DOMAIN; B CHAIN C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. JACKSON LAB,BAR HARBOR,ME. RP HARRIS, N (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115, USA. FU NCRR NIH HHS [MO1 RR 02172]; NHLBI NIH HHS [P01 HL 43510]; PHS HHS [R01 A1 123786] NR 71 TC 22 Z9 22 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 28 PY 1994 VL 198 IS 2 BP 682 EP 692 DI 10.1006/bbrc.1994.1099 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MT888 UT WOS:A1994MT88800040 PM 8297379 ER PT J AU SPRINGER, TA AF SPRINGER, TA TI TRAFFIC SIGNALS FOR LYMPHOCYTE RECIRCULATION AND LEUKOCYTE EMIGRATION - THE MULTISTEP PARADIGM SO CELL LA English DT Review ID CELL-ADHESION MOLECULE-1; MEMORY T-CELLS; NODE HOMING RECEPTOR; MONOCLONAL-ANTIBODY; VASCULAR ADDRESSIN; COUNTER-RECEPTOR; PERTUSSIS TOXIN; CHEMOTACTIC FACTORS; MIGRATION PATHWAYS; ENDOTHELIAL-CELLS RP SPRINGER, TA (reprint author), HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA31798, CA31799]; NIAID NIH HHS [AI31921] NR 105 TC 5884 Z9 5985 U1 25 U2 206 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JAN 28 PY 1994 VL 76 IS 2 BP 301 EP 314 DI 10.1016/0092-8674(94)90337-9 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA MU678 UT WOS:A1994MU67800013 PM 7507411 ER PT J AU RUBIN, E PANTAZIS, P BHARTI, A TOPPMEYER, D GIOVANELLA, B KUFE, D AF RUBIN, E PANTAZIS, P BHARTI, A TOPPMEYER, D GIOVANELLA, B KUFE, D TI IDENTIFICATION OF A MUTANT HUMAN TOPOISOMERASE-I WITH INTACT CATALYTIC ACTIVITY AND RESISTANCE TO 9-NITRO-CAMPTOTHECIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TARGETING ANTITUMOR DRUGS; TUMOR-CELL LINES; PROTEIN-KINASE-C; EUKARYOTIC TOPOISOMERASE; DNA TOPOISOMERASES; MELANOMA-CELLS; SITE TYROSINE; LUNG-CANCER; CAMPTOTHECIN; EXPRESSION AB Human U-937 myeloid leukemia cells were selected for resistance to increasing concentrations of the camptothecin derivative, 9-nitro-20(S)camptothecin (9-NC). The isolated single cell clone, designated U-937/CR, was approximately 20-fold resistant to 9-NC. Analysis of topoisomerase I (topo I) gene expression in U-937/CR cells demonstrated similar mRNA levels as compared with U-937 cells. Immunoblotting with an anti-topo I serum revealed reactive proteins at 100, 75, and 67 kDa which were expressed at the same level in the parental and 9-NC-resistant clones. These cell lines also demonstrated similar levels of topo I catalytic activity as determined by assaying nuclear extracts for relaxation of supercoiled plasmid DNA. In contrast, catalytic assays performed in the presence of 9-NC demonstrated that topo I activity from U-937/CR cells was approximately 10-fold more resistant than that from U-937 cells. Nucleotide sequencing of topo I cDNAs revealed the substitution of phenylalanine (TTC) at residue 361 in U-937 cells with serine (TCC) in the 9-NC-resistant clone. Expression and partial purification of the mutant topo I protein in Escherichia coli demonstrated resistance of this enzyme to 9-NC in catalytic assays. Taken together, these findings identify a novel mutation in topo I which confers resistance to 9-NC and support the involvemenT of this region in the interaction between topo I and 9-NC. C1 ST JOSEPH HOSP,STEHLIN FDN CANC RES,HOUSTON,TX 77002. RP RUBIN, E (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [1K08CA01664-01, CA38493] NR 55 TC 121 Z9 122 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 28 PY 1994 VL 269 IS 4 BP 2433 EP 2439 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MV432 UT WOS:A1994MV43200017 PM 8300570 ER PT J AU MOHRAZ, M ARYSTARKHOVA, E SWEADNER, KJ AF MOHRAZ, M ARYSTARKHOVA, E SWEADNER, KJ TI IMMUNOELECTRON MICROSCOPY OF EPITOPES ON NA,K-ATPASE CATALYTIC SUBUNIT - IMPLICATIONS FOR THE TRANSMEMBRANE ORGANIZATION OF THE C-TERMINAL DOMAIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADENOSINE-TRIPHOSPHATASE; SARCOPLASMIC-RETICULUM; MONOCLONAL-ANTIBODY; OUABAIN BINDING; OUTER MEDULLA; ION-TRANSPORT; NA+,K+-ATPASE; IDENTIFICATION; TOPOLOGY; VESICLES AB The transmembrane folding of the alpha subunit of Na,K-ATPase was studied by using immunoelectron microscopy to determine whether monoclonal antibodies with defined epitopes bind to the extracellular or cytoplasmic surface. In double labeling experiments, an antibody and a reference marker were bound to purified membrane-associated Na,K-ATPase and were visualized by employing colloidal gold particles of two different sizes. Wheat germ agglutinin and a previously characterized monoclonal antibody were used as control markers for the exoplasmic and cytoplasmic surfaces, respectively. Three antibodies, VG4, VG2, and IIC9, unambiguously bound to the extracellular surface. Previously IIC9 had been assigned to the cytoplasmic surface because, in immunofluorescence studies, it stained intact cells only when they were detergent-permeabilized. To investigate the basis for this contradiction, a third assay for sidedness was used: competition binding in solution to right-side-out renal medullary vesicles. IIC9 was found to bind to the extracellular surface of sealed vesicles, but only in certain experimental conditions. It was concluded that IIC9 has an epitope that is not always accessible and that in this instance, studies of binding to intact and detergent-treated cells had given misleading results. An extracellular disposition for all three antibodies is not compatible with existing folding models, and new models are presented. C1 MASSACHUSETTS GEN HOSP,WELLMAN 4,FRUIT ST,BOSTON,MA 02114. NYU,DEPT CELL BIOL,NEW YORK,NY 10016. MM SHEMYAKIN INST BIOORGAN CHEM,117871 MOSCOW,RUSSIA. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL36271]; NIGMS NIH HHS [GM35399] NR 24 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 28 PY 1994 VL 269 IS 4 BP 2929 EP 2936 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MV432 UT WOS:A1994MV43200083 PM 7507930 ER PT J AU ZOU, ZQ ANISOWICZ, A HENDRIX, MJC THOR, A NEVEU, M SHENG, SJ RAFIDI, K SEFTOR, E SAGER, R AF ZOU, ZQ ANISOWICZ, A HENDRIX, MJC THOR, A NEVEU, M SHENG, SJ RAFIDI, K SEFTOR, E SAGER, R TI MASPIN, A SERPIN WITH TUMOR-SUPPRESSING ACTIVITY IN HUMAN MAMMARY EPITHELIAL-CELLS SO SCIENCE LA English DT Article ID DOWN-REGULATION; MESSENGER-RNAS; METASTASIS; GENES; LINES AB A gene encoding a protein related to the serpin family of protease inhibitors was identified as a candidate tumor suppressor gene that may play a role in human breast cancer. The gene product, called maspin, is expressed in normal mammary epithelial cells but not in most mammary carcinoma cell lines. Transfection of MDA-MB-435 mammary carcinoma cells with the maspin gene did not alter the cells' growth properties in vitro, but reduced the cells' ability to induce tumors and metastasize in nude mice and to invade through a basement membrane matrix in vitro. Analysis of human breast cancer specimens revealed that loss of maspin expression occurred most frequently in advanced cancers. These results support the hypothesis that maspin functions as a tumor suppressor. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,44 BINNEY ST,BOSTON,MA 02115. UNIV ARIZONA,CTR CANC,TUCSON,AZ 85724. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FU NCI NIH HHS [CA39814, P01 CA22427, R01 CA59702] NR 21 TC 711 Z9 767 U1 2 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 28 PY 1994 VL 263 IS 5146 BP 526 EP 529 DI 10.1126/science.8290962 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MT966 UT WOS:A1994MT96600035 PM 8290962 ER PT J AU PERICAKVANCE, MA CORDER, EH SAUNDERS, AM GASKILL, PC STRITTMATTER, WJ ROSES, AD SCHMECHEL, DE SMALL, GW HAINES, JL AF PERICAKVANCE, MA CORDER, EH SAUNDERS, AM GASKILL, PC STRITTMATTER, WJ ROSES, AD SCHMECHEL, DE SMALL, GW HAINES, JL TI ALZHEIMERS-DISEASE AND POSSIBLE GENE INTERACTION - RESPONSE SO SCIENCE LA English DT Article C1 DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DEPT NEUROL,DURHAM,NC 27710. DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DEPT NEUROBIOL,DURHAM,NC 27710. UNIV CALIF LOS ANGELES,CTR HLTH SCI,NEUROPSYCHIAT INST & HOSP,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. RP PERICAKVANCE, MA (reprint author), DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DEPT MED,DURHAM,NC 27710, USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 28 PY 1994 VL 263 IS 5146 BP 537 EP 537 DI 10.1126/science.263.5146.537-a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MT966 UT WOS:A1994MT96600040 ER PT J AU ROSENBAUM, DS JACKSON, LE SMITH, JM GARAN, H RUSKIN, JN COHEN, RJ AF ROSENBAUM, DS JACKSON, LE SMITH, JM GARAN, H RUSKIN, JN COHEN, RJ TI ELECTRICAL ALTERNANS AND VULNERABILITY TO VENTRICULAR ARRHYTHMIAS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ST-SEGMENT ALTERNANS; MYOCARDIAL-INFARCTION; T-WAVE; SUDDEN-DEATH; FIBRILLATION; MORPHOLOGY AB Background. Although electrical alternans (alternating amplitude from beat to beat on the electrocardiogram) has been associated with ventricular arrhythmias in many clinical settings, its physiologic importance and prognostic implications remain unknown. Methods. To test the hypothesis that electrical alternans is a marker of vulnerability to ventricular arrhythmias, we developed a technique to detect subtle alternation in the morphologic features of the electrocardiogram (which would not be detectable by visual inspection of the electrocardiogram). In a group of 83 patients referred for diagnostic electrophysiologic testing, we prospectively examined whether levels of alternans predicted vulnerability to arrhythmias as defined by the outcome of electrophysiologic testing and arrhythmia-free survival. Results. Sustained ventricular arrhythmias were induced during electrophysiologic testing in 32 of the patients (39 percent). In this group, low-level electrical alternans (a beat-to-beat change in amplitude of < 15 muV) was detected over a broad range of physiologic heart rates (from 95 to 150 beats per minute) and primarily involved the ST segment and the T wave (i.e., the phase of repolarization). Alternans during repolarization was a significant and independent predictor of inducible arrhythmias on electrophysiologic testing (sensitivity, 81 percent; specificity, 84 percent; relative risk, 5.2). Of 66 patients followed for up to 20 months, 13 had arrhythmic events. Alternans affecting the T wave and inducibility of ventricular arrhythmias were significant and essentially equivalent predictors of survival without arrhythmia (P<0.001). Actuarial survival without arrhythmia at 20 months was significantly lower among the patients with T-wave alternans (19 percent) than among the patients without T-wave alternans (94 percent). Conclusions. Electrical alternans affecting the ST segment and T wave is common among patients at increased risk for ventricular arrhythmias. Subtle electrical alternans on the electrocardiogram may serve as a noninvasive marker of vulnerability to ventricular arrhythmias. C1 CASE WESTERN RESERVE UNIV,DEPT MED,CLEVELAND,OH 44106. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02138. RP ROSENBAUM, DS (reprint author), CASE WESTERN RESERVE UNIV,DEPT BIOMED ENGN,WICKENDEN BLDG,RM 504,CLEVELAND,OH 44106, USA. FU NHLBI NIH HHS [R01-HL39291] NR 32 TC 784 Z9 807 U1 1 U2 9 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 27 PY 1994 VL 330 IS 4 BP 235 EP 241 DI 10.1056/NEJM199401273300402 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MR496 UT WOS:A1994MR49600002 PM 8272084 ER PT J AU BASGOZ, N MATTIA, AR PEGUES, DA MULLEN, MP AF BASGOZ, N MATTIA, AR PEGUES, DA MULLEN, MP TI A 38-YEAR-OLD MAN WITH AIDS AND THE RECENT-ONSET OF DIARRHEA, HEMATOCHEZIA, FEVER, AND PULMONARY-INFILTRATES - DISSEMINATED HISTOPLASMOSIS - ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID PNEUMOCYSTIS-CARINII PNEUMONIA; IMMUNE-DEFICIENCY-SYNDROME; LARGE URBAN OUTBREAK; VIRUS-INFECTION; CLINICAL-FEATURES; TUBERCULOSIS; DIAGNOSIS; CAPSULATUM; RISK; IDENTIFICATION C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BASGOZ, N (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 50 TC 5 Z9 5 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 27 PY 1994 VL 330 IS 4 BP 273 EP 280 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA MR496 UT WOS:A1994MR49600008 ER PT J AU EMANUEL, LL EMANUEL, EJ STOECKLE, JD HUMMEL, LR BARRY, MJ AF EMANUEL, LL EMANUEL, EJ STOECKLE, JD HUMMEL, LR BARRY, MJ TI ADVANCE DIRECTIVES - STABILITY OF PATIENTS TREATMENT CHOICES SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LIFE-SUSTAINING TREATMENTS; DECISION-MAKING; HEALTH-CARE; PREFERENCES; PROXIES; AGREEMENT; RESIDENTS; KAPPA AB Background: Advance directives are intended to extend patient autonomy into periods of mental incompetence. However, for advance directives to fulfill this objective, patients' choices must be reasonably consistent over time. Thus, we assessed the stability of the advance treatment decisions of patients and members of the public. Methods: In a prospective cohort study of 495 outpatients and 102 members of the public, we studied the stability of scenarios and treatment-specific choices. Subjects completed an advance directive, which included four illness scenarios with 11 treatment choices in each, as part of a questionnaire. A second interview was completed by 296 patients and 78 members of the public after 6 to 12 months; 154 patients completed a third interview after a further 6 to 12 months. We assessed stability by comparing each choice between interviews. Results: Stability of choices was moderately high among patients (pooled K=0.39) and members of the public (pooled K=0.48). Stability improved with repeat interview (pooled K=0.47 among patients). Patients who had discussions with their physicians showed more improvement (K=0.57) than others. Patients had a wide range of personal stability levels (O% to 100%), but individuals starting out stable rarely became less so (93% of the patients with 85% to 100% stability maintained this level of stability on the third interview). Hospitalized patients showed no significant difference in stability at the second interview, but their stability was not improved at the third interview. Conclusions: Our findings generally support the use of advance directives. Most people made moderately stable decisions when using scenario- and treatment-specific directives, and stability improved after they reviewed the decisions, especially among those who had discussions with their physicians. Recent hospitalization did not decrease stability, although it appeared to reduce the improvement that others achieved with repeat interview. These findings suggest that advance directives can be relied on 1 to 2 years after completion to reflect a patient's choices. C1 MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114. DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA. RP EMANUEL, LL (reprint author), HARVARD UNIV,SCH MED,DIV MED ETH,641 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU AHRQ HHS [HS06120] NR 40 TC 111 Z9 112 U1 3 U2 6 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 JAN 24 PY 1994 VL 154 IS 2 BP 209 EP 217 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA MR236 UT WOS:A1994MR23600011 PM 8285816 ER PT J AU SINGER, DE AF SINGER, DE TI ASPIRIN AND PREVENTION OF STROKE SO LANCET LA English DT Letter ID ATRIAL-FIBRILLATION; WARFARIN RP SINGER, DE (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,GEN INTERNAL MED UNIT,BOSTON,MA 02114, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JAN 22 PY 1994 VL 343 IS 8891 BP 233 EP 234 DI 10.1016/S0140-6736(94)91018-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA MT332 UT WOS:A1994MT33200037 PM 7904684 ER PT J AU RAVICHANDRAN, KS BURAKOFF, SJ AF RAVICHANDRAN, KS BURAKOFF, SJ TI THE ADAPTER PROTEIN SHC INTERACTS WITH THE INTERLEUKIN-2 (IL-2) RECEPTOR UPON IL-2 STIMULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SIGNAL TRANSDUCTION; TYROSINE KINASES; BETA-SUBUNIT; ACTIVATION; REGION; CHAIN; IDENTIFICATION; ASSOCIATION; BINDING; DOMAIN AB Binding of interleukin-2 (IL-2) to the IL-2 receptor (IL-2R) stimulates Src family kinases, tyrosine phosphorylation of several proteins, conversion of Ras to its active GTP-bound form, and eventually c-fos, c-jun, and c-myc induction. The IL-2Rbeta chain plays a crucial role in IL-2R signaling. Within the cytoplasmic domain of the beta chain, a region essential for mitogenesis and another involved in binding the Src family kinase Lck have been defined. The beta chain itself is tyrosine-phosphorylated upon IL-2 stimulation. Since the adapter protein Shc acts upstream of Ras and is involved in T cell receptor-mediated Ras activation, we examined the role of Shc in IL-2 signaling. Shc was found to be tyrosine-phosphorylated upon IL-2 stimulation in CTLL-20 cells. After its phosphorylation, Shc interacted with another adapter protein, Grb2, and, via Grb2, with the Ras GTP/GDP exchange factor mSOS. After IL-2 stimulation, Shc also associated with the IL-2Rbeta chain. Thus, during IL-2 signaling, the interaction of Shc with the IL-2Rbeta chain and its simultaneous association with Grb2 and mSOS may couple IL-2R stimulation to Ras signaling. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. FU NIAID NIH HHS [AI-17258] NR 23 TC 130 Z9 131 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 1994 VL 269 IS 3 BP 1599 EP 1602 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800009 PM 8294403 ER PT J AU HORITA, DA HAJDUK, PJ GOETINCK, PF LERNER, LE AF HORITA, DA HAJDUK, PJ GOETINCK, PF LERNER, LE TI NMR-STUDIES OF PEPTIDES DERIVED FROM THE PUTATIVE BINDING REGIONS OF CARTILAGE PROTEINS - NO EVIDENCE FOR BINDING TO HYALURONAN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LINK PROTEIN; PROTEOGLYCANS; DOMAINS; ACID AB Previous work has implicated sequences within the tandem repeats of cartilage link protein in the interaction of link protein with hyaluronan. This conclusion was based on competitive inhibition experiments using synthetic peptides (Goetinck, P. F., Stirpe, N. S., Tsonis, P. A., and Carlone, D. (1987) J. Cell Biol. 105, 2403-2407). Further investigation of this system using high resolution nuclear magnetic resonance, circular dichroism, and competitive inhibition with other peptides indicates that the previously observed inhibition of link protein-hyaluronan binding was not caused by peptide-hyaluronan interactions. Instead, nonspecific aggregation of the peptides with link protein is proposed to account for all of the experimental data. Consequently, there is no direct experimental evidence to support the conclusion that these sequences in the tandem repeats of link protein are responsible for the link protein-hyaluronan interaction. If these peptides do represent the hyaluronan binding regions of link protein, these results imply a highly structure-dependent interaction between link protein and hyaluronan. Conformational analysis of the peptides using two-dimensional nuclear Overhauser spectroscopy indicates that the linear peptides do not adopt any stable secondary structure. However, several residues in the disulfide-looped peptides exhibit connectivities, suggesting a relatively long-lived extended chain conformation, consistent with predictions of secondary structure based on sequence analysis. C1 UNIV WISCONSIN,DEPT CHEM,1101 UNIV AVE,MADISON,WI 53706. MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. FU NCRR NIH HHS [SIO RRO 4981]; NIAMS NIH HHS [R29 AR39801]; NICHD NIH HHS [HD 22016] NR 16 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 21 PY 1994 VL 269 IS 3 BP 1699 EP 1704 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800027 PM 8294417 ER PT J AU KAPELLER, R PRASAD, KVS JANSSEN, O HOU, W SCHAFFHAUSEN, BS RUDD, CE CANTLEY, LC AF KAPELLER, R PRASAD, KVS JANSSEN, O HOU, W SCHAFFHAUSEN, BS RUDD, CE CANTLEY, LC TI IDENTIFICATION OF 2 SH3-BINDING MOTIFS IN THE REGULATORY SUBUNIT OF PHOSPHATIDYLINOSITOL 3-KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; RECEPTOR TYROSINE KINASES; SIGNAL TRANSDUCTION; SH3 DOMAINS; C-SRC; GROWTH; PI3-KINASE; EXPRESSION; P60C-SRC; BINDING AB Src homology 3 (SH3) domains have been recently shown to bind to proline-rich sequences contained in 3BP1, 3BP2, and SOS. In a recent study we demonstrated that phosphatidylinositol 3-kinase (PI 3-kinase) associates with the Fyn SH3 domain. Here we show that p85, the regulatory subunit of PI 3-kinase, binds directly to the SH3 domains of Abl, Lck, Fyn, and p85 itself. An examination of p85 amino acid sequence revealed two proline-rich sequences in its N-terminal region similar to those present in 3BP1, 3BP2, and SOS. To test whether these sequences mediate the association of p85 with SH3 domains two peptides with amino acid composition corresponding to the p85alpha proline-rich sequences were synthesized and used in competition assays. Both peptides worked equally well in inhibiting the binding of PI 3-kinase activity and p85alpha to Fyn SH3 domain, whereas a control peptide had no effect. These results indicate that, as in 3BP1 and SOS, the proline-rich sequences in p85 mediate its interaction with SH3 domains. These results also suggest that the SH3 domain of p85 may ''self-associate'' with the proline-rich motifs of the same subunit as part of the PI 3-kinase regulatory mechanism. C1 TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. RP KAPELLER, R (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,DIV SIGNAL TRANSDUCT,200 LONGWOOD AVE EQRF,BOSTON,MA 02215, USA. RI Janssen, Ottmar/E-9735-2010; Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [GM 36624, GM 41890, R01 GM041890] NR 35 TC 125 Z9 125 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 JAN 21 PY 1994 VL 269 IS 3 BP 1927 EP 1933 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800058 PM 8294442 ER PT J AU GAIRE, M MAGBANUA, Z MCDONNELL, S MCNEIL, L LOVETT, DH MATRISIAN, LM AF GAIRE, M MAGBANUA, Z MCDONNELL, S MCNEIL, L LOVETT, DH MATRISIAN, LM TI STRUCTURE AND EXPRESSION OF THE HUMAN GENE FOR THE MATRIX METALLOPROTEINASE MATRILYSIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RHEUMATOID SYNOVIAL FIBROBLASTS; COLLAGENASE GENE; HUMAN STROMELYSIN; IV COLLAGENASE; CHROMOSOMAL LOCALIZATION; PHORBOL INDUCTION; MESSENGER-RNA; GROWTH-FACTOR; PROMOTER; TRANSIN AB Matrilysin, a member of the matrix metalloproteinase family, is structurally different from the other matrix metalloproteinases by virtue of the absence of a conserved COOH-terminal protein domain. In addition, matrilysin mRNA is regulated in a specific and distinct manner in normal and malignant tissues. Analysis of the genomic structure of the human matrilysin gene revealed that the organization of the first five exons is highly conserved among the different members of the matrix metalloproteinase family, but that matrilysin contains an atypical sixth exon. The promoter region of the matrilysin gene has several features that are conserved among several other matrix metalloproteinase family members, including the presence of TATA, AP-1, and PEA3 elements. Comparison of the expression of the human matrilysin promoter with rat stromelysin promoter/chloramphenicol acetyltransferase constructs in HeLa cells revealed that constructs containing AP-1 and PEA3 elements respond similarly to epidermal growth factor and tumor promoter (12-O-tetradecanoylphorbol-13-acetate) induction, but that the addition of upstream stromelysin sequences results in an increased transcriptional activity not observed with upstream matrilysin sequences. The similarities and differences observed between the promoters of matrilysin and the other metalloproteinases may provide insights into the molecular mechanisms that regulate the expression of this family of enzymes as a whole and the factors that distinguish the expression patterns of individual family members. C1 VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37232. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO VET AFFAIRS MED CTR,DEPT MED,SAN FRANCISCO,CA 94121. FU NCI NIH HHS [CA46843]; NIDDK NIH HHS [DK39776] NR 51 TC 214 Z9 217 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 JAN 21 PY 1994 VL 269 IS 3 BP 2032 EP 2040 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800074 PM 8294454 ER PT J AU TILLOTSON, LG WANG, TC BRAND, SJ AF TILLOTSON, LG WANG, TC BRAND, SJ TI ACTIVATION OF GASTRIN TRANSCRIPTION IN PANCREATIC INSULINOMA CELLS BY A CACC PROMOTER ELEMENT AND A 70-KDA SEQUENCE-SPECIFIC DNA-BINDING PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; GENE-TRANSCRIPTION; ISLET CELL; ENHANCER-BINDING; CONTROL REGION; GLUCAGON GENE; EXPRESSION; UPSTREAM; IDENTIFICATION; DOMAINS AB Gastrin gene expression in the pancreatic islets is developmentally regulated and occurs largely during fetal life. Deletional analysis of transiently transfected rat insulinoma cells with gastrin 5'-flanking sequences in luciferase reporter genes demonstrated that the gastrin promoter sequence proximal to -111 base pairs (bp) contains the cis-regulatory elements necessary for maximal transcription. Mutational analysis identified the sequence CCCCACCCCA (-109 to -100 bp) as a positive cis-regulatory element (CACC) located 5' to a previously described negative element (-100 to -90 bp) and E-box positive element at -82 bp. Multimers of the CACC element in a heterologous promoter activated transcription independent of the other cis-regulatory elements. CACC binding proteins were purified from insulinoma cell nuclear extracts by cation exchange and affinity chromatography. Southwestern blot of nuclear extracts identified a 70-kDa CACC-binding protein. Mutational analysis of the CACC element showed a close correlation between DNA binding of this protein and transcriptional activation. Transcriptional activation by multimers of the CACC element in a heterologous promoter was detected in a variety of cell lines but was strongest in those of islet lineage. Likewise, the presence of the 70-kDa CACC-binding protein was found in many cell lines but was most abundant in the insulinoma cells. The CACC-binding protein has not been previously identified among the known pancreatic regulatory factors and may have an important role in the developmental expression of gastrin. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP TILLOTSON, LG (reprint author), MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,JACKSON 7,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK42147] NR 58 TC 22 Z9 22 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 JAN 21 PY 1994 VL 269 IS 3 BP 2234 EP 2240 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800101 PM 8294480 ER PT J AU TAKAYAMA, K MITCHELL, DH DIN, ZZ MUKERJEE, P LI, C COLEMAN, DL AF TAKAYAMA, K MITCHELL, DH DIN, ZZ MUKERJEE, P LI, C COLEMAN, DL TI MONOMERIC RE LIPOPOLYSACCHARIDE FROM ESCHERICHIA-COLI IS MORE ACTIVE THAN THE AGGREGATED FORM IN THE LIMULUS AMEBOCYTE LYSATE ASSAY AND IN INDUCING EGR-1 MESSENGER-RNA IN MURINE PERITONEAL-MACROPHAGES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTOXIN; DIFFERENTIATION; PROTEIN; GROWTH AB Using the equilibrium dialysis apparatus, an aqueous suspension of predominantly aggregated Re lipopolysaccharide (ReLPS) from Escherichia coli D31 m4 (99.9% at 82.5 muM) can be processed to yield a solution of monomeric ReLPS at a saturation concentration of 77 ng/ml (3.4 x 10(-8) m). We compared the in vitro biological activities of these two physically distinct types of ReLPS preparations in two select assays, reaction in the Limulus amebocyte lysate (LAL) assay and induction of Egr-1 mRNA in macrophages. These assays were chosen for their rapid response times and relatively short incubation periods. The monomeric ReLPS was 179- and 1000-fold more active than the aggregated ReLPS preparation in the LAL assay and induction of Egr-1 mRNA by thioglycollate-elicited murine peritoneal macrophages, respectively. These results clearly showed that the monomeric ReLPS is the more active form. The lower biological activities of the aggregated ReLPS preparation might be due to the presence of a small amount of monomeric ReLPS (0.01-0.6%) produced during its preparation and the incubation periods in the biological assays. Thus, aggregated ReLPS may be relatively inactive. C1 UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. UNIV WISCONSIN,SCH PHARM,MADISON,WI 53706. UNIV COLORADO,HLTH SCI CTR,DIV INFECT DIS,DENVER,CO 80262. VET ADM MED CTR,INFECT DIS SECT,DENVER,CO 80220. RP TAKAYAMA, K (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NIGMS NIH HHS [GM-36054] NR 18 TC 90 Z9 91 U1 0 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 JAN 21 PY 1994 VL 269 IS 3 BP 2241 EP 2244 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR988 UT WOS:A1994MR98800102 PM 8294481 ER PT J AU RAJAGOPALAN, S XU, YH BRENNER, MB AF RAJAGOPALAN, S XU, YH BRENNER, MB TI RETENTION OF UNASSEMBLED COMPONENTS OF INTEGRAL MEMBRANE-PROTEINS BY CALNEXIN SO SCIENCE LA English DT Article ID T-CELL RECEPTOR; PRE-GOLGI DEGRADATION; ENDOPLASMIC-RETICULUM; ANTIGEN RECEPTORS; COMPLEX; BINDING; IDENTIFICATION; GLYCOPROTEINS; MOLECULES; REQUIRES AB Quality control mechanisms prevent the cell surface expression of incompletely assembled multisubunit receptors such as the T cell receptor (TCR). The molecular chaperone function of calnexin (IP90, p88), a 90-kilodalton protein that resides in the endoplasmic reticulum (ER), in the retention of representative chains of the TCR-CD3 complex in the ER was tested. Truncation mutants of calnexin, when transiently expressed in COS cells, were exported from the ER and either accumulated in the Golgi or progressed to the cell surface. CD3 epsilon chains cotransfected with the forms of calnexin that were not retained in the ER exited the ER and colocalized with calnexin. Since engineered calnexin determined the intracellular localization of the proteins associated with it, it is concluded that calnexin interacts with incompletely assembled TCR components and retains them in the ER. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,ELECTRON MICROSCOPY & STRUCT MOLEC BIOL LAB,BOSTON,MA 02115. RP RAJAGOPALAN, S (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RHEUMATOL & IMMUNOL,LYMPHOCYTE BIOL SECT,BOSTON,MA 02115, USA. NR 27 TC 212 Z9 212 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JAN 21 PY 1994 VL 263 IS 5145 BP 387 EP 390 DI 10.1126/science.8278814 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MT034 UT WOS:A1994MT03400037 PM 8278814 ER PT J AU KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A CHIANG, CM ROEDER, RG BRADY, JN AF KASHANCHI, F PIRAS, G RADONOVICH, MF DUVALL, JF FATTAEY, A CHIANG, CM ROEDER, RG BRADY, JN TI DIRECT INTERACTION OF HUMAN TFIID WITH THE HIV-1 TRANSACTIVATOR TAT SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; III TRANSCRIPTION FACTOR; RNA POLYMERASE-II; BINDING PROTEIN; ELONGATION; COMPONENTS; ACTIVATION; COMPLEXES; PROMOTER; INVITRO AB THE tat gene of the human immunodeficiency virus (HIV) plays a central role in the activation and life cycle of HIV. The tat protein (Tat) specifically transactivates HIV transcription in vivo and in vitro1-8, exerting its effects at the level of transcriptional initiation and elongation. Here we report that Tat binds directly to the basal transcription factor TFIID. The transcriptional activity of HeLa extracts was depleted after chromatography on a rat affinity column, which specifically retained the polymerase II-specific factor TFIID: Direct interaction of Tat with holo-TFIID, composed of TATA-binding protein (TBP) and associated factors (TAFs), was observed. Tat binds, through amino acids 36-50, directly to the TBP subunit of TFIID. Our results suggest that Tat may transduce upstream or downstream regulatory signals by direct interaction with the basal transcription factor TFIID. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. ROCKEFELLER UNIV,NEW YORK,NY 10021. RP KASHANCHI, F (reprint author), NCI,MOLEC VIROL LAB,BETHESDA,MD 20892, USA. NR 30 TC 241 Z9 243 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JAN 20 PY 1994 VL 367 IS 6460 BP 295 EP 299 DI 10.1038/367295a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR494 UT WOS:A1994MR49400063 PM 8121496 ER PT J AU COREY, DP BREAKEFIELD, XO AF COREY, DP BREAKEFIELD, XO TI TRANSCRIPTION FACTORS INNER-EAR DEVELOPMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID THYROID-HORMONE RECEPTOR; NERVE GROWTH-FACTOR; HUP2 PAIRED DOMAIN; WAARDENBURG SYNDROME; GENERALIZED RESISTANCE; RESPONSE ELEMENT; MESSENGER-RNAS; MOUSE EMBRYOS; HUMAN HOMOLOG; BETA GENE C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP COREY, DP (reprint author), HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,BOSTON,MA 02114, USA. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [R01 DC000304] NR 60 TC 36 Z9 36 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 1994 VL 91 IS 2 BP 433 EP 436 DI 10.1073/pnas.91.2.433 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR989 UT WOS:A1994MR98900002 PM 8290543 ER PT J AU HIRAYAMA, F CLARK, SC OGAWA, M AF HIRAYAMA, F CLARK, SC OGAWA, M TI NEGATIVE REGULATION OF EARLY B-LYMPHOPOIESIS BY INTERLEUKIN-3 AND INTERLEUKIN-1-ALPHA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MULTIPOTENTIAL HEMATOPOIETIC PROGENITORS; COLONY-STIMULATING FACTOR; BONE-MARROW CULTURES; FACTOR-I; INTERLEUKIN-3-DEPENDENT PROLIFERATION; SYNERGISTIC INTERACTIONS; MURINE HEMATOPOIESIS; C-KIT; CELLS; GROWTH AB We recently developed a two-step methyl cellulose culture system for murine lymphohemopoietic progenitors that are capable of differentiation along the myeloid and B-lymphoid lineages. In this system, two-factor combinations, which include steel factor plus interleukin (IL) 6, IL-11, or granulocyte colony-stimulating factor effectively supported the lymphomyeloid potential of primary colonies. Interestingly, IL-3 could neither replace nor act synergistically with steel factor in maintaining the B-lymphoid potential of the primary colonies although the frequency of colony formation was the same with IL-3 and steel factor. We now report that addition of IL-3 or IL-1 alpha to a permissive system suppresses the B-lymphoid potential of primitive progenitor cells in primary culture in dose-dependent fashion. In vivo transfer of the primary colonies to scid mice confirmed the suppressive effects of 11-3 and IL-1 alpha. In addition, IL-1 alpha inhibited pre-B-cell colony formation in the secondary culture. Once pre-B-cell colonies had formed in secondary culture, neither factor affected the proliferation of the pre-B cells. These results suggest negative regulatory roles for IL-3 and IL-1 alpha in early stages of B lymphopoiesis. C1 MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29425. GENET INST INC,CAMBRIDGE,MA 02140. FU NIDDK NIH HHS [DK32294] NR 33 TC 82 Z9 83 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 1994 VL 91 IS 2 BP 469 EP 473 DI 10.1073/pnas.91.2.469 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR989 UT WOS:A1994MR98900010 PM 7507246 ER PT J AU HINDS, PW DOWDY, SF EATON, EN ARNOLD, A WEINBERG, RA AF HINDS, PW DOWDY, SF EATON, EN ARNOLD, A WEINBERG, RA TI FUNCTION OF A HUMAN CYCLIN GENE AS AN ONCOGENE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-CYCLE; TRANSCRIPTION FACTOR; CANDIDATE ONCOGENE; CHROMOSOME 11Q13; DNA-REPLICATION; E1A PRODUCTS; TRANSFORMATION; PROTEIN; IDENTIFICATION; EXPRESSION AB The cyclin D1 (PRAD1, CCND1) gene is affected by translocations and amplification in the genomes of a number of human tumors, suggesting that these changes confer growth advantage on developing tumor cell clones. We show here that in cultured cells, a cDNA clone of the cyclin D1 gene can contribute to cell transformation by complementing a defective adenovirus E1A oncogene. In such cells, this candidate oncogene indeed functions like an oncogene, suggesting a similar role in tumor progression in vivo. C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [R35 CA39826] NR 48 TC 465 Z9 475 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 1994 VL 91 IS 2 BP 709 EP 713 DI 10.1073/pnas.91.2.709 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR989 UT WOS:A1994MR98900058 PM 8290586 ER PT J AU KELLY, KJ WILLIAMS, WW COLVIN, RB BONVENTRE, JV AF KELLY, KJ WILLIAMS, WW COLVIN, RB BONVENTRE, JV TI ANTIBODY TO INTERCELLULAR-ADHESION MOLECULE-1 PROTECTS THE KIDNEY AGAINST ISCHEMIC-INJURY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ACUTE RENAL FAILURE; ISCHEMIA-REPERFUSION INJURY; ADHESION MOLECULE RECEPTORS; INTEGRINS ID MONOCLONAL-ANTIBODIES; REPERFUSION INJURY; MYOCARDIAL-ISCHEMIA; ENDOTHELIAL-CELLS; RENAL-FAILURE; RAT; NEUTROPHIL; ADHERENCE; ACCUMULATION; INVITRO AB The pathophysiology of ischemic acute renal failure is complex, and the role of leukocyte adhesion in this process is not well defined. A monoclonal antibody (mAb) against intracellular adhesion molecule 1 (anti-ICAM-1), administered at the time of bilateral renal ischemia in the rat, prevented both functional impairment and histologic changes of acute renal failure. Plasma creatinine measured (mg/dl) 24 hr after 30 min of ischemia was 0.61 +/- 0.05 in the anti-ICAM-1-treated animals compared with 2.4 +/- 0.14 (P < 0.0001) in the vehicle-treated ischemic group. Forty-eight hours after ischemia, creatinine values were 0.46 +/- 0.05 and 2.03 +/- 0.22 (P < 0.0001) in anti-ICAM-1 and vehicle-treated groups, respectively. A low dose of anti-ICAM-1 that was itself nonprotective, when given with partially protective doses of a mAb against lymphocyte function-associated antigen-1 (anti-LFA-1), acted synergistically to prevent renal failure. Anti-ICAM-1 mAb also protected the kidney when administered 0.5 or 2 hr but not 8 hr after restoration of blood flow and when the ischemic period was extended to 40 min. Ischemia-induced increases in tissue myeloperoxidase, a marker of neutrophil infiltration, were mitigated with anti-ICAM-1 treatment. Thus, anti-ICAM-1 mAb protected the kidney against ischemic renal failure, even when the antibody was administered after the ischemic period. These results suggest a critical role for leukocytes and adhesion molecules in the pathophysiology of ischemic injury and may have important therapeutic implications. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,PATHOL SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. RP KELLY, KJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK39773, T32DK07540] NR 29 TC 370 Z9 381 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 JAN 18 PY 1994 VL 91 IS 2 BP 812 EP 816 DI 10.1073/pnas.91.2.812 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR989 UT WOS:A1994MR98900079 PM 7904759 ER PT J AU UNSAL, H YAKICIER, C MARCAIS, C KEW, M VOLKMANN, M ZENTGRAF, H ISSELBACHER, KJ OZTURK, M AF UNSAL, H YAKICIER, C MARCAIS, C KEW, M VOLKMANN, M ZENTGRAF, H ISSELBACHER, KJ OZTURK, M TI GENETIC-HETEROGENEITY OF HEPATOCELLULAR-CARCINOMA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE P53 TUMOR SUPPRESSOR GENE; HEPATITIS B VIRUS; AFLATOXINS; MUTATION; LIVER CANCER ID HEPATITIS-B VIRUS; P53 GENE; RETINOBLASTOMA GENES; SOUTHERN-AFRICA; HUMAN CANCERS; CELL-LINE; MUTATION; LIVER; EPIDEMIOLOGY; AFLATOXIN AB We studied 80 hepatocellular carcinomas from three continents For p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 45% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-type of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function. C1 CTR LEON BERARD,INSERM,CJF 9302,ONCOL MOLEC LAB,F-69008 LYON,FRANCE. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. UNIV WITWATERSRAND,JOHANNESBURG,SOUTH AFRICA. UNIV HEIDELBERG,DEPT INTERNAL MED,W-6900 HEIDELBERG,GERMANY. DEUTSCH KREBSFORSCHUNGSZENTRUM,HEIDELBERG,GERMANY. RI ozturk, mehmet/G-3330-2014 FU NCI NIH HHS [CA-54567] NR 49 TC 140 Z9 141 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 18 PY 1994 VL 91 IS 2 BP 822 EP 826 DI 10.1073/pnas.91.2.822 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA MR989 UT WOS:A1994MR98900081 PM 8290606 ER PT J AU HYMAN, BT REITER, J MOSS, M ROSENE, D PANDYA, D AF HYMAN, BT REITER, J MOSS, M ROSENE, D PANDYA, D TI EXTRACELLULAR SIGNAL-REGULATED KINASE (MAP KINASE) IMMUNOREACTIVITY IN THE RHESUS-MONKEY BRAIN SO NEUROSCIENCE LETTERS LA English DT Article DE MAP KINASE; ERK; IMMUNOHISTOCHEMISTRY; RHESUS MONKEY; ALZHEIMERS DISEASE ID ALZHEIMERS-DISEASE; TAU-PROTEIN; PHOSPHORYLATION; TYROSINE; INSULIN; FAMILY AB Extracellular signal regulated kinases (ERKs) are a recently cloned family of genes that encode the MAP kinase protein kinases. They are highly expressed in brain and are believed to play an integral role in neural cellular responses to receptor activation. A role for ERKs has been postulated in Alzheimer's disease, where they have been implicated in phosphorylation of tau in neurofibrillary tangles. We explored the neuroanatomic distribution of ERK immunoreactivity in the rhesus monkey brain. The hippocampal formation, especially the messy fiber zone and the molecular layer of the dentate gyrus are the most heavily immunostained areas. Cerebral cortex is, in general, more intensely stained in the supragranular layers. The caudate, putamen, and substantia nigra contain more immunoreactivity than the claustrum, globus pallidus, or thalamus with the exception of midline thalamic structures. These results suggest a marked regional and laminar distribution of ERKs in the primate brain. C1 BOSTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,BOSTON,MA 02118. EDITH NOURSE ROGERS MEM VET ADM HOSP,BEDFORD,MA. RP HYMAN, BT (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114, USA. RI Rosene, Douglas/G-1973-2015 FU NIA NIH HHS [NIA P01-AG-00001, NIA AG08487] NR 19 TC 13 Z9 13 U1 0 U2 1 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 JAN 17 PY 1994 VL 166 IS 1 BP 113 EP 116 DI 10.1016/0304-3940(94)90853-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA MW548 UT WOS:A1994MW54800028 PM 8190351 ER PT J AU NATOWICZ, MR BEJJANI, B AF NATOWICZ, MR BEJJANI, B TI GENETIC-DISORDERS THAT MASQUERADE AS MULTIPLE-SCLEROSIS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Review DE MULTIPLE SCLEROSIS; GENETICS ID HEREDITARY OPTIC NEUROPATHY; SUBACUTE NECROTIZING ENCEPHALOMYELOPATHY; GLOBOID-CELL LEUKODYSTROPHY; MITOCHONDRIAL-DNA MUTATION; ARYLSULFATASE-A PSEUDODEFICIENCY; PYRUVATE-DEHYDROGENASE COMPLEX; POLYGLUCOSAN BODY DISEASE; TRANSFER RNALEU(UUR) GENE; ALPHA-GALACTOSIDASE-A; C OXIDASE DEFICIENCY AB There are many genetic disorders that have signs and symptoms suggestive of multiple sclerosis and that may easily be overlooked in the evaluation of both adult and pediatric multiple sclerosis patients. The recognition of a genetic disorder as the cause of a patient's ''multiple sclerosis'' phenotype has important implications not only for the patient, but often also for others in the patient's family who may be at risk for the same disease. We present here a review of single gene disorders that can masquerade as multiple sclerosis. For each disorder, the major clinical and biochemical characteristics are discussed, together with the appropriate testing to screen for and confirm the diagnosis. In addition, guidelines are presented for when to suspect an underlying genetic condition in a patient with a diagnosis of definite or probable multiple sclerosis. The great variety of genetic disorders that can masquerade as multiple sclerosis and the many implications of a genetic diagnosis underscore the importance of recognizing genocopies of multiple sclerosis. (C) 1994 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV N CAROLINA HOSP,DEPT PEDIAT,CHAPEL HILL,NC. RP NATOWICZ, MR (reprint author), EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,200 TRAPELO RD,WALTHAM,MA 02254, USA. NR 277 TC 22 Z9 22 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JAN 15 PY 1994 VL 49 IS 2 BP 149 EP 169 DI 10.1002/ajmg.1320490202 PG 21 WC Genetics & Heredity SC Genetics & Heredity GA MP330 UT WOS:A1994MP33000001 PM 8116663 ER PT J AU BHANDARI, B GRANDALIANO, G ABBOUD, HE AF BHANDARI, B GRANDALIANO, G ABBOUD, HE TI PLATELET-DERIVED GROWTH-FACTOR (PDGF) BB HOMODIMER REGULATES PDGF A-CHAIN AND PDGF B-CHAIN GENE-TRANSCRIPTION IN HUMAN MESANGIAL CELLS SO BIOCHEMICAL JOURNAL LA English DT Article ID FACTOR-A-CHAIN; MICROVASCULAR ENDOTHELIAL-CELLS; CULTURED 3T3-L1 ADIPOCYTES; C-SIS GENE; GLUTAMINE-SYNTHETASE GENE; HUMAN GLIOBLASTOMA CELLS; MESSENGER-RNA STABILITY; CYCLIC-AMP; FACTOR-BETA; EXPRESSION AB Mesangial cells express platelet-derived growth factor (PDGF) A- and B-chain mRNA and release PDGF. Several polypeptide growth factors, including PDGF itself, induce PDGF A- and B-chain mRNA abundance. To understand the molecular mechanisms associated with the changes in mRNA abundance, we measured the effects of PDGF BB homodimer on PDGF A- and B-chain gene transcription in cultured mesangial cells. The data demonstrate 2- and 4-fold increases in PDGF A-chain gene transcription in response to PDGF BB homodimer at 5 and 24 h time points respectively. PDGF B-chain gene transcription was also induced approximately 3-fold at 2, 5 and 24 h time points in response to treatment with PDGF BB homodimer. The effect of PDGF BB on the half-life of PDGF A- as well as PDGF B-chain mRNA was measured directly by the pulse-chase method. There was no effect on PDGF A-chain mRNA half-life whereas PDGF B-chain mRNA half-life was increased 1.5-fold. These studies indicate that, in human mesangial cells, the increase in the levels of PDGF A- and B-chain mRNA in response to PDGF-receptor(s) activation is mediated at the level of gene transcription. In addition, the regulation of PDGF B- but not PDGF A-chain gene involves increased mRNA stability. Mesangial cells are a useful model for studying molecular mechanisms of PDGF-gene regulation in non-transformed human cells. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP BHANDARI, B (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEPHROL,SAN ANTONIO,TX 78284, USA. RI Grandaliano, Giuseppe/G-2963-2012 FU NIDDK NIH HHS [DK 43988] NR 34 TC 8 Z9 8 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JAN 15 PY 1994 VL 297 BP 385 EP 388 PN 2 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MT892 UT WOS:A1994MT89200021 PM 8297346 ER PT J AU YANG, KD MIZOBUCHI, T KHARBANDA, SM DATTA, R HUBERMAN, E KUFE, DW STONE, RM AF YANG, KD MIZOBUCHI, T KHARBANDA, SM DATTA, R HUBERMAN, E KUFE, DW STONE, RM TI ALL-TRANS-RETINOIC ACID REVERSES PHORBOL ESTER RESISTANCE IN A HUMAN MYELOID-LEUKEMIA CELL-LINE SO BLOOD LA English DT Article ID PROTEIN-KINASE-C; ACUTE PROMYELOCYTIC LEUKEMIA; HUMAN MONOCYTIC DIFFERENTIATION; GENE-EXPRESSION; HL-60 CELLS; T(15-17) TRANSLOCATION; TUMOR PROMOTERS; MESSENGER-RNA; BETA-GENE; RAR-ALPHA C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,44 BINNEY ST,BOSTON,MA 02115. ARGONNE NATL LAB,CTR MECHANIST BIOL & BIOTECHNOL,ARGONNE,IL 60439. UNIV CHICAGO,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. TRI SERV GEN HOSP,DEPT PEDIAT,TAIPEI,TAIWAN. FU NCI NIH HHS [CA42802, CA34283, KO8-CA-01352] NR 46 TC 38 Z9 39 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 JAN 15 PY 1994 VL 83 IS 2 BP 490 EP 496 PG 7 WC Hematology SC Hematology GA MR986 UT WOS:A1994MR98600025 PM 8286746 ER PT J AU BALLEN, KK GILLILAND, DG KALISH, LA SHULMAN, LN AF BALLEN, KK GILLILAND, DG KALISH, LA SHULMAN, LN TI BONE-MARROW DYSPLASIA IN PATIENTS WITH NEWLY-DIAGNOSED ACUTE MYELOGENOUS LEUKEMIA DOES NOT CORRELATE WITH HISTORY OF MYELODYSPLASIA OR WITH REMISSION RATE AND SURVIVAL SO CANCER LA English DT Article DE ACUTE MYELOGENOUS LEUKEMIA; MYELODYSPLASIA; BONE MARROW ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ACUTE MYELOBLASTIC-LEUKEMIA; ADULT PATIENTS; THERAPY; DIFFERENTIATION; CLASSIFICATION; ABNORMALITIES; CHEMOTHERAPY; FEATURES AB Background. The records and initial bone marrow studies of 106 patients with newly diagnosed acute myelogenous leukemia (AML) were analyzed retrospectively to determine whether bone marrow dysplasia was predictive of a previous myelodysplastic disorder or correlated with remission rate and survival. Methods. Bone marrow aspirates and biopsy specimens were reviewed in a blinded fashion; dysplasia was assessed in as objective a manner as possible by numerically scoring nine specific findings: erythrocyte multinuclearity, nuclear fragmentation, megaloblastic characteristics, leukocyte granulation abnormalities and nuclear malformations, Pelger-Huet cells, and megakaryocytic dysplasia (mononuclear megakaryocytes, micromegakaryocytes, and megakaryocytes with multiple distinct nuclei). Results. Dysplasia of the megakaryocytic line was seen in 34% of patients; 70% of the patients had erythrocyte dysplasia; and 68% had leukocyte dysplasia. Pelger-Huet cells were seen in bone marrow of 35% of the patients. Overall dysplasia score and specific dysplastic findings such as Pelger-Huet cells did not correlate with a known history of myelodysplasia (P = 0.47), cytogenetic abnormalities (P = 0.35), prior chemotherapy treatment with or without alkylating agents (P = 1.00), previous malignant disorders such as polycythemia vera (P = 1.00), remission rate (P = 0.93), or survival (P = 0.42). Multivariate analysis confirmed known independent risk factors for remission in this patient population, including age (P = 0.04), history of prior chemotherapy (P = 0.04), abnormalities in chromosomes 5, 7, or 8 (P = 0.02), and type of antileukemia therapy (P < 0.001). Conclusions. Bone marrow dysplasia is common in patients with AML and does not correlate with a history of myelodysplasia or predict outcome when patients are treated with standard intensive AML therapy. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. RP BALLEN, KK (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 33 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 1994 VL 73 IS 2 BP 314 EP 321 DI 10.1002/1097-0142(19940115)73:2<314::AID-CNCR2820730214>3.0.CO;2-C PG 8 WC Oncology SC Oncology GA MR381 UT WOS:A1994MR38100013 PM 8293394 ER PT J AU GALE, KE ANDERSEN, JW TORMEY, DC MANSOUR, EG DAVIS, TE HORTON, J WOLTER, JM SMITH, TJ CUMMINGS, FJ AF GALE, KE ANDERSEN, JW TORMEY, DC MANSOUR, EG DAVIS, TE HORTON, J WOLTER, JM SMITH, TJ CUMMINGS, FJ TI HORMONAL TREATMENT FOR METASTATIC BREAST-CANCER - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP PHASE-III TRIAL COMPARING AMINOGLUTETHIMIDE TO TAMOXIFEN SO CANCER LA English DT Article DE BREAST; CANCER; AMINOGLUTETHIMIDE; TAMOXIFEN; ADRENALECTOMY; WOMEN; RANDOMIZED ID THERAPY AB Background. Tamoxifen and aminoglutethimide are two hormone therapies reported to be effective palliative approaches for patients with metastatic breast cancer. The current trial was designed to evaluate their relative therapeutic effectiveness. Methods. Two hundred forty-nine postmenopausal women with advanced breast cancer were randomized in an Eastern Cooperative Oncology Group (ECOG) Phase III study to treatment with adrenalectomy, aminoglutethimide, or tamoxifen with crossover to alternate therapy if disease progressed. Adrenalectomy was dropped as a treatment after 2 years because of low patient accrual. Results. There were 216 evaluable patients entered in the study with 108 initially randomized to aminoglutethimide and 108 to receive tamoxifen therapy. The overall response rate for aminoglutethimide was 45%, and for tamoxifen it was 27%. One institution had a response rate of 60% with aminoglutethimide and only 4% with tamoxifen, whereas all of the other institutions combined had a response rate of 41% with aminoglutethimide and 34% with tamoxifen. Eighty-seven evaluable patients crossed over to the other drug (44 to aminoglutethimide and 43 to tamoxifen). There was a 36% response rate to aminoglutethimide and 19% to tamoxifen, with stable disease in 36% of both groups. The overall survival rates were identical. Toxicity was greater with aminoglutethimide (dermatitis) but was not life-threatening. Glucocorticoid support with either dexamethasone or hydrocortisone was acceptable. Conclusions. Both aminoglutethimide and tamoxifen produced responses in postmenopausal patients with breast cancer, and a significant number of crossover responses were observed. Of interest in this randomized study was the observation that one institution had a markedly different response rate on induction, reinforcing the need for multi-institution trials in Phase III studies. C1 ST JOSEPHS HOSP HLTH CTR,SYRACUSE,NY. HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,BOSTON,MA 02115. AMC CANC RES CTR,DENVER,CO. CASE WESTERN RESERVE UNIV,CLEVELAND,OH. H LEE MOFFITT CANC CTR,TAMPA,FL. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. TUFTS UNIV,NEW ENGLAND MED CTR HOSP,BOSTON,MA 02111. BROWN UNIV,PROVIDENCE,RI. ROGER WILLIAMS GEN HOSP,PROVIDENCE,RI. FU NCI NIH HHS [CA 23318, CA 14548, CA 21115] NR 21 TC 60 Z9 61 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JAN 15 PY 1994 VL 73 IS 2 BP 354 EP 361 DI 10.1002/1097-0142(19940115)73:2<354::AID-CNCR2820730220>3.0.CO;2-J PG 8 WC Oncology SC Oncology GA MR381 UT WOS:A1994MR38100019 PM 8293400 ER PT J AU KEYOMARSI, K OLEARY, N MOLNAR, G LEES, E FINGERT, HJ PARDEE, AB AF KEYOMARSI, K OLEARY, N MOLNAR, G LEES, E FINGERT, HJ PARDEE, AB TI CYCLIN-E, A POTENTIAL PROGNOSTIC MARKER FOR BREAST-CANCER SO CANCER RESEARCH LA English DT Note ID DNA POLYMERASE-DELTA; CELL-CYCLE; CANDIDATE ONCOGENE; AUXILIARY PROTEIN; AMPLIFICATION; GENE; 11Q13; OVEREXPRESSION; SURVIVAL; PHASE AB A fundamental cause of cancer is changed properties of genetic material, which may deregulate normal development of the tissue or provide selective growth advantage to the tumor cell. This deregulation of cell proliferation results from altered production of a handful of proteins that play key roles in progression through the eukaryotic cell cycle. Some of these proteins include tumor suppressor genes or oncogenes. However, no one general change or alteration of a critical gene has yet been found in all cancers. Using surgical material obtained from patients with various malignancies, we show that breast cancers and other solid tumors, as well as malignant lymphocytes from patients with lymphatic leukemia, show severe quantitative and qualitative alterations in cyclin E protein production independent of the S-phase fraction of the samples. Hence, these alterations represent a true difference between normal versus tumor tissue. In addition, in breast cancer, the alterations in cyclin E expression become progressively worse with increasing stage and grade of the tumor, suggesting its potential use as a new prognostic marker. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. ST ELIZABETHS MED CTR,BOSTON,MA 02135. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA08949-02]; NIGMS NIH HHS [GM 24571] NR 34 TC 342 Z9 353 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1994 VL 54 IS 2 BP 380 EP 385 PG 6 WC Oncology SC Oncology GA MR217 UT WOS:A1994MR21700015 PM 7903908 ER PT J AU DENG, G CHEN, LC SCHOTT, DR THOR, A BHARGAVA, V LJUNG, BM CHEW, K SMITH, HS AF DENG, G CHEN, LC SCHOTT, DR THOR, A BHARGAVA, V LJUNG, BM CHEW, K SMITH, HS TI LOSS OF HETEROZYGOSITY AND P53 GENE-MUTATIONS IN BREAST-CANCER SO CANCER RESEARCH LA English DT Article ID TUMOR SUPPRESSOR GENES; WILD-TYPE P53; CELL-CYCLE CONTROL; A MOUSE CELLS; MUTANT P53; GEL-ELECTROPHORESIS; PROTEIN P53; NORMAL 3T3; DNA; EXPRESSION AB Immunopositivity for the p53 tumor suppressor gene product was evaluated in 133 breast cancers and compared to loss of heterozygosity (LOH) at various chromosomal loci. The validity of p53 immunopositivity as an indicator for p53 mutations was verified using two molecular assays of p53 mutations: single stranded conformational polymorphism (32 cases) and/or direct sequencing (14 cases). Immunopositivity was highly specific for mutations, since all of 15 strongly immunopositive tumors (>10% of the cells are positive) and seven of nine cases with borderline immunopositivity had mutations by molecular analysis but were somewhat lower in sensitivity, p53 mutations being also detected in three of 23 (13%) immunonegative cases. LOH was measured at loci on the following chromosomes (1p,q; 2p; 3p; 7q; 11p,q; 13q; 16q; 17p; 18p,q; and 22q) by Southern blotting, polymerase chain reaction amplification of restriction fragment length polymorphisms, or repetitive cytidine and adenine stretches (CA repeats). There was no association between p53 mutations and one measure of genomic instability, namely, high incidence of overall LOH. In contrast, p53 mutations strongly associated with LOH at two specific loci, 3p24-26 (P < 0.001) and 7q31 (P < 0.05). There was no association between p53 mutations and LOH at 17p (site of the p53 gene), suggesting that breast cancers often have only one defective allele of the p53 gene. C1 PACIFIC MED CTR,GERALDINE BRUSH CANC RES INST,2330 CLAY ST,ROOM 201,SAN FRANCISCO,CA 94115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. FU NCI NIH HHS [P01 CA44768] NR 68 TC 129 Z9 140 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 JAN 15 PY 1994 VL 54 IS 2 BP 499 EP 505 PG 7 WC Oncology SC Oncology GA MR217 UT WOS:A1994MR21700034 PM 8275488 ER PT J AU VAILLY, J VERRANDO, P CHAMPLIAUD, MF GERECKE, D WAGMAN, DW BAUDOIN, C ABERDAM, D BURGESON, R BAUER, E ORTONNE, JP AF VAILLY, J VERRANDO, P CHAMPLIAUD, MF GERECKE, D WAGMAN, DW BAUDOIN, C ABERDAM, D BURGESON, R BAUER, E ORTONNE, JP TI THE 100-KDA CHAIN OF NICEIN/KALININ IS A LAMININ B2 CHAIN VARIANT SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; HUMAN EPIDERMAL KERATINOCYTES; MONOCLONAL-ANTIBODY GB3; BASEMENT-MEMBRANES; ACID; SEQUENCE; PROTEIN; HEMIDESMOSOMES; PURIFICATION; EXPRESSION AB We have isolated the basement membrane component nicein and performed rotary-shadow analyses using electron microscopy that showed the presence of two forms (I and II) of the protein. Molecular cloning of the cDNA that codes for the 100-kDa chain of the protein revealed that the sequence matches those independently identified for the 105-155-kDa subunit of kalinin, a recently identified basement membrane component. These data demonstrate that nicein and kalinin contain an identical chain. The length of the open reading frame in the cDNA (approximate to 5200 nucleotides) and amino acid sequences obtained from the N-terminus of the 105-kDa kalinin chain showed the occurrence of a precursor polypeptide. This immature polypeptide is probably related to form I, observed by rotary shadowing, while the mature form is related to form II. It is noteworthy that nicein/kalinin subunits share discrete sequence similarities with the B2 chain of human laminin, but with a cleavage occurring within domain III that eliminates domains IV and V from the final product. The sequence of this subunit is nearly identical to that of B2t, a recently described polypeptide supposed to be related to a new laminin variant. Since nicein/kalinin expression is specifically impaired in the severe genodermatosis Herlitz junctional epidermolysis bullosa, the role and structure of this tissue-restricted laminin Variant is crucial for the understanding of epidermal-dermal adhesion. C1 UNIV NICE,UFR MED,RECH DERMATOL LAB,F-06107 NICE 2,FRANCE. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA. STANFORD UNIV,SCH MED,DEPT DERMATOL,STANFORD,CA. RI Aberdam, Daniel/G-3299-2013 NR 34 TC 107 Z9 108 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JAN 15 PY 1994 VL 219 IS 1-2 BP 209 EP 218 DI 10.1111/j.1432-1033.1994.tb19932.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR858 UT WOS:A1994MR85800024 PM 8306988 ER PT J AU ATTWOOD, J CHIANO, M COLLINS, A DONISKELLER, H DRACOPOLI, N FOUNTAIN, J FALK, C GOUDIE, D GUSELLA, J HAINES, J ARMOUR, JAL JEFFREYS, AJ KWIATKOWSKI, D LATHROP, M MATISE, T NORTHRUP, H PERICAKVANCE, MA PHILLIPS, J RETIEF, A ROBSON, E SHIELDS, D SLAUGENHAUPT, S VERGNAUD, G WEBER, J WEISSENBACH, J WHITE, R YATES, J POVEY, S AF ATTWOOD, J CHIANO, M COLLINS, A DONISKELLER, H DRACOPOLI, N FOUNTAIN, J FALK, C GOUDIE, D GUSELLA, J HAINES, J ARMOUR, JAL JEFFREYS, AJ KWIATKOWSKI, D LATHROP, M MATISE, T NORTHRUP, H PERICAKVANCE, MA PHILLIPS, J RETIEF, A ROBSON, E SHIELDS, D SLAUGENHAUPT, S VERGNAUD, G WEBER, J WEISSENBACH, J WHITE, R YATES, J POVEY, S TI CEPH CONSORTIUM MAP OF CHROMOSOME-9 SO GENOMICS LA English DT Article ID LINKAGE MAP; GORLIN SYNDROME; HUMAN GENOME; GENE; DELETIONS; MELANOMA AB This paper describes the Centre d'Etude du Polymorphisme Humain (CEPH) consortium linkage map of chromosome 9. A total of 124 markers were typed in the CEPH family DNAs by 14 contributing laboratories; of these, 42 loci are ordered on the map with likelihood support of at least 1000:1. The uniquely placed markers include 31 that can be typed by PCR. A further 28 markers that can be typed by PCR are approximately positioned on the map. Multilocus linkage analysis with CRI-MAP has produced male, female, and sex-averaged maps extending for 176, 237, and 209 cM, respectively, while sex-averaged maps produced with MAPMAKER and the multiple two-point program MAP extended for 170 and 129 cM, respectively. The male map contains only two intervals greater than 10 cM, and the mean genetic distance between the 42 uniquely placed loci is 4.3 cM. However, no markers were available to anchor the map at either telomere or the centromere. The results confirm the high level of interference suggested by chiasma maps of chromosome 9. Detailed meiotic breakpoints for three of the families are shown. These can be used to provide rapid placement of any new marker without the need for statistical analysis. (C) 1994 Academic Press, Inc. C1 UNIV CAMBRIDGE, DEPT PATHOL, CAMBRIDGE CB2 1QP, CAMBS, ENGLAND. PRINCESS ANNE HOSP, CRC, DEPT CHILD HLTH, GENET EPIDEMIOL RES GRP, SOUTHAMPTON SO9 4HA, HANTS, ENGLAND. WASHINGTON UNIV, SCH MED, DEPT GENET, ST LOUIS, MO 63110 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. MIT, CTR CANC RES, CAMBRIDGE, MA 02139 USA. NEW YORK BLOOD CTR, POPULAT GENET LAB, NEW YORK, NY 10021 USA. MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, NEUROGENET LAB, BOSTON, MA 02114 USA. UNIV LEICESTER, DEPT GENET, LEICESTER LE1 7RH, ENGLAND. BRIGHAM & WOMENS HOSP, DIV EXPTL MED, BOSTON, MA 02115 USA. CEPH, F-75010 PARIS, FRANCE. UNIV PITTSBURGH, PITTSBURGH, PA 15261 USA. UNIV TEXAS, SCH MED, DEPT PEDIAT, DIV GENET, HOUSTON, TX 77225 USA. DUKE UNIV, MED CTR, DIV NEUROL, DURHAM, NC 27710 USA. VANDERBILT UNIV, MED CTR, DIV GENET, NASHVILLE, TN 37232 USA. UNIV STELLENBOSCH, FAC AGR SCI, DEPT GENET, STELLENBOSCH 7600, SOUTH AFRICA. UCL, DEPT GENET & BIOMETRY, GALTON LAB, LONDON NW1 2HE, ENGLAND. CTR ETUD BOUCHET, F-91710 VERT LE PETIT, FRANCE. MARSHFIELD MED RES FDN, MARSHFIELD, WI 54449 USA. INST PASTEUR, F-75724 PARIS 15, FRANCE. UNIV UTAH, HOWARD HUGHES MED INST, SALT LAKE CITY, UT 84112 USA. RP ATTWOOD, J (reprint author), UCL, GALTON LAB,MRC,HUMAN BIOCHEM GENET UNIT, WOLFSON HOUSE, 4 STEPHENSON WAY, LONDON NW1 2HE, ENGLAND. RI Collins, Andrew/A-6595-2010; Haines, Jonathan/C-3374-2012; Vergnaud, Gilles/P-1304-2015 OI Collins, Andrew/0000-0001-7108-0771; Vergnaud, Gilles/0000-0003-0913-194X FU NHGRI NIH HHS [HG00598]; NIGMS NIH HHS [GM29177]; Wellcome Trust NR 36 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD JAN 15 PY 1994 VL 19 IS 2 BP 203 EP 214 DI 10.1006/geno.1994.1049 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NA603 UT WOS:A1994NA60300001 PM 8188250 ER PT J AU NGUYEN, L KNIPE, DM FINBERG, RW AF NGUYEN, L KNIPE, DM FINBERG, RW TI MECHANISM OF VIRUS-INDUCED IG SUBCLASS SHIFTS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA; ANTIBODY-RESPONSE; HUMAN LYMPHOTOXIN; PROTEIN ANTIGENS; GENETIC-EVIDENCE; T-CELLS; INFECTION; MICE; ACTIVATION; SUPERANTIGEN AB Infection of mice with live viruses leads to a dramatic increase in the amount of IgG2a Ig with a consequent shift in the ratio of IgG1/IgG2a. To examine the Ig subclass shift induced by viral infection, we challenged mice with live virus, inactivated virus, or replication-defective mutant viruses that were able to infect cells and produce some viral proteins but were not able to complete a replicative cycle. While killed (or inactivated) virus was capable of inducing HSV-specific antibody, it did not stimulate a shift in the subclass of the total Ig. Replication-defective mutant viruses that fail to express a functional ICP8 or ICP27 protein, but not a mutant expressing a defective ICP4 protein, were able to stimulate the shift. Thus, only a portion of the lytic cycle is sufficient to induce the shift. At least part of the effect is mediated by IFN-gamma. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI20381, AI24010] NR 50 TC 61 Z9 62 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 1994 VL 152 IS 2 BP 478 EP 484 PG 7 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600012 PM 8283031 ER PT J AU RASMUSSEN, RA COUNTS, SL DALEY, JF SCHLOSSMAN, SF AF RASMUSSEN, RA COUNTS, SL DALEY, JF SCHLOSSMAN, SF TI ISOLATION AND CHARACTERIZATION OF CD6- T-CELLS FROM PERIPHERAL-BLOOD SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER CELLS; BONE-MARROW TRANSPLANTATION; HUMAN LYMPHOCYTES-T; MONOCLONAL-ANTIBODIES; STRUCTURALLY DISTINCT; B-CELLS; RECEPTOR; ANTIGEN; ACTIVATION; EXPRESSION AB Antibodies to the CD6 Ag have been described as having pan-T cell reactivity. We have recently demonstrated, however, that after treatment of PBL with an anti-CD6-blocked ricin-conjugated immunotoxin, clonal populations of CD3+, CD6- cells can be identified. Herein we show that through dual parameter staining of freshly isolated E-rosette+ cells, an average of 5 to 6% of either CD3+ or CD5+ cells express little or no CD6 on their surface. After negative selection by antibody-coated paramagnetic bead depletion, expanded CD6- T cells were shown to be CD1a-, CD2+, CD3+, CD5+, CD16-, CD56 -, TCR-gamma/delta-, and consisted of both CD4+ and CD8+ cells. Furthermore, staining of digitonin permeabilized cells showed no cytoplasmic expression of the CD6 Ag and CD6 mRNA was not detected by Northern blot analysis. Identical staining patterns were observed for T cell clones isolated through bead depletion or immunotoxin treatment and expanded with either PHA or immobilized anti-CD3 mAb. It was also found that, relative to unfractionated T cells, the surface expression of CD5 was significantly diminished on CD6- T cells. Functionally, freshly isolated CD6- T cells showed substantially reduced alloreactivity in MLR compared with unfractionated E-rosette' cells, yet both gave similar proliferative responses to either PHA or soluble tetanus toxin Ag. We conclude that there exists a minor subpopulation of mature T cells in peripheral blood that lack CD6. The diminished alloreactivity of these cells may help to explain the low incidence of graft-vs-host disease, despite high levels of engraftment, that has been reported in allogeneic bone marrow transplant patients receiving marrow treated with anti-CD6 (Tl 2) mAb plus C'. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP RASMUSSEN, RA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI33485-01] NR 41 TC 24 Z9 24 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 JAN 15 PY 1994 VL 152 IS 2 BP 527 EP 536 PG 10 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600017 PM 7904289 ER PT J AU GERARD, NP GERARD, C AF GERARD, NP GERARD, C TI RECEPTOR-DEPENDENT INTERNALIZATION OF PLATELET-ACTIVATING-FACTOR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMA-MEMBRANE; POLYMORPHONUCLEAR LEUKOCYTES; SURFACE EXPRESSION; MOLECULAR-CLONING; HUMAN-NEUTROPHILS; RABBIT PLATELETS; CDNA; RELEASE; BINDING; ANAPHYLATOXIN AB A human neutrophil platelet-activating factor (PAF) receptor expressed in transfected cells was utilized to study receptor-dependent interactions with the ligand. This receptor displays ligand-binding properties comparable with those observed with naturally occurring receptor-positive cells when binding experiments are performed using COS-7 cells at 4-degrees-C. The ligand-receptor interaction is markedly temperature dependent, with approximately 10-fold more [H-3]PAF specifically associated with the cells at 37-degrees-C than at 4-degrees-C. Such temperature dependence is not observed with other ligand-receptor pairs. At 37-degrees-C essentially all the cell-associated PAF appears to be internalized and incorporated into a phospholipid pool. In the absence of transfected receptor no specific binding is detected in COS-7 cells at 4-degrees-C, and at 37-degrees-C, no significant ligand internalization is observed. The epitope-tagged fusion protein, Flag-PAF receptor, was used to track the receptor independently of ligand binding, and showed that the receptor protein expressed on the cell surface is not influenced by temperature alone. Incubation with PAF at 37-degrees-C resulted in the disappearance of approximately 20% of the Flag-PAF receptor epitope from the cell surface relative to cells incubated without PAF or cells preincubated with or without PAF at 4-degrees-C. Ligand internalization in PAF receptor-transfected cells is inhibited by the receptor antagonist, WEB 2086, further supporting the receptor-dependence of this action. Stimulation of untransfected cells with phorbol ester, or C5a receptor-transfected cells with C5a, shows minimal increase in PAF internalization relative to PAF receptor-transfected cells, another feature that distinguishes the receptor-dependent pathway. These data suggest that in the COS-7 cell system PAF internalization is dependent on expression of the PAF receptor, and that the apparently nonspecific uptake observed in human neutrophils and other cells may involve receptor-independent mechanisms. C1 CHILDRENS HOSP MED CTR,INA SUE PERLMUTTER LAB,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,THORNDIKE LAB,BOSTON,MA 02115. RP GERARD, NP (reprint author), BETH ISRAEL HOSP,DEPT MED,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NHLBI NIH HHS [HL 36162] NR 42 TC 19 Z9 20 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 JAN 15 PY 1994 VL 152 IS 2 BP 793 EP 800 PG 8 WC Immunology SC Immunology GA MR216 UT WOS:A1994MR21600044 PM 8283052 ER PT J AU BLAND, MM MCDONALD, OB CARRERA, AC AF BLAND, MM MCDONALD, OB CARRERA, AC TI P56LCK PHOSPHORYLATION BY CA-2+/CALMODULIN-DEPENDENT PROTEIN-KINASE TYPE-II SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MULTIFUNCTIONAL CAM KINASE; CELL ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; TYROSINE KINASES; SRC FAMILY; ACTIVATION; BRAIN; EXPRESSION; CALCIUM; GR C1 WELLCOME RES LABS,RES TRIANGLE PK,NC 27709. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA. OI Carrera, Ana/0000-0002-3999-5434 NR 33 TC 14 Z9 14 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 14 PY 1994 VL 198 IS 1 BP 67 EP 73 DI 10.1006/bbrc.1994.1010 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA MQ932 UT WOS:A1994MQ93200010 PM 8292050 ER PT J AU KHARBANDA, S SALEEM, A EMOTO, Y STONE, R RAPP, U KUFE, D AF KHARBANDA, S SALEEM, A EMOTO, Y STONE, R RAPP, U KUFE, D TI ACTIVATION OF RAF-1 AND MITOGEN-ACTIVATED PROTEIN-KINASES DURING MONOCYTIC DIFFERENTIATION OF HUMAN MYELOID-LEUKEMIA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR NECROSIS FACTOR; C-JUN EXPRESSION; GROWTH-FACTOR; OKADAIC ACID; MAP KINASE; GENE-EXPRESSION; FOS GENE; MOLECULAR-CLONING; INDUCTION AB Treatment of human myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C (PKC), is associated with induction of monocytic differentiation. Since PKC can act immediately upstream to the cytoplasmic Raf-1 serine/threonine protein kinase, we studied activation of Raf-1 during induction of the differentiated monocytic phenotype. The results demonstrate that Raf-1 is activated during TPA-induced monocytic differentiation of HL-60 cells. In contrast, there was little effect of TPA on this kinase in an HL-60 variant, designated HL-525, which is resistant to TPA-induced differentiation. Treatment of both HL-60 and HL-525 cells with okadaic acid, an inhibitor of serine/threonine protein phosphatases 1 and 2A, was associated with Raf-1 activation and induction of the monocytic phenotype. Since Raf-1 can activate the mitogen-activated protein (MAP) kinases, we also studied the relationship between MAP kinase activation and monocytic differentiation. Treatment of HL-60, but not HL-525, cells with TPA was associated with increased MAP kinase activity as determined by phosphorylation of myelin basic protein and the c-Jun Y peptide. Okadaic acid-induced differentiation of both HL-60 and HL-525 cells was similarly accompanied by increases in MAP kinase activity. These findings indicated that activation of Raf-1/MAP kinase signaling is associated with induction of a differentiated monocytic phenotype and that okadaic acid by-passes a defect in this cascade in TPA-treated HL-525 cells. While recent studies have shown that HL-525 cells are deficient in PKCbeta, the present results demonstrate that PKCbeta expression is up-regulated in the HL-525 variant by treatment with retinoic acid. The results also demonstrate that retinoic acid-treated HL-525 cells respond to TPA with activation of Raf-1 and MAP kinase, as well as induction of monocytic differentiation. Taken together, the results indicate that activation of Raf-1/MAP kinase signaling is associated with monocytic differentiation and that stimulation of serine/threonine protein phosphorylation by TPA or okadaic acid is sufficient for reversal of the leukemic HL-60 phenotype. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP KHARBANDA, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA42802] NR 56 TC 110 Z9 110 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 1994 VL 269 IS 2 BP 872 EP 878 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR220 UT WOS:A1994MR22000019 PM 8288641 ER PT J AU HENSON, JW AF HENSON, JW TI REGULATION OF THE GLIAL-SPECIFIC JC VIRUS EARLY PROMOTER BY THE TRANSCRIPTION FACTOR-SP1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR FACTOR-I; GENE-EXPRESSION; BRAIN-CELLS; PROTEIN; SP1; DNA; ENHANCER; SEQUENCES; SITES; MOUSE AB The regulation of glial-specific JC virus early gene expression was addressed by functional dissection of a previously uncharacterized form of the JC virus promoter (MH-1). The MH-1 promoter directed 31-fold higher reporter gene expression in U87MG glioma cells than in HeLa cells in a transient transfection assay. Transfection of promoter constructs containing proximal or proximal plus upstream regions revealed that reporter gene expression was activated by both proximal and tandem repeat regions in glioma cells. The proximal region contains a guanine-rich sequence, the GA box, which was found to regulate the promoter, and was recognized specifically by the transcription factor Spl. The GA box is also present in the promoters of three glial-specific cellular genes. Together with paired AP-1 and NF-1 sites in the tandem repeats, the GA box is part of a motif that is conserved between several glial-specific promoters, and is thus a potential determinant of glial-specific gene expression. These results delineate the promoter regions required for activation of the MH-I JC virus promoter, suggest a new determinant of glial specificity, and establish a model for the investigation of combinatorial activation of a glial-specific viral promoter. RP HENSON, JW (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NINDS NIH HHS [NS 01650] NR 23 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 1994 VL 269 IS 2 BP 1046 EP 1050 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR220 UT WOS:A1994MR22000044 PM 8288559 ER PT J AU DOU, QP ZHAO, SC LEVIN, AH WANG, J HELIN, K PARDEE, AB AF DOU, QP ZHAO, SC LEVIN, AH WANG, J HELIN, K PARDEE, AB TI G1/S-REGULATED E2F-CONTAINING PROTEIN COMPLEXES BIND TO THE MOUSE THYMIDINE KINASE GENE PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR E2F; CELL-CYCLE REGULATION; RETINOBLASTOMA PROTEIN; LABILE PROTEIN; DNA-BINDING; PRODUCT; EXPRESSION; GROWTH; PHASE; SITE AB By performing DNase I footprint analysis, we had identified three distinct protein binding sequences (MT1, MT2, and MT3) located on the mouse thymidine kinase (TK) upstream promoter (Dou, Q.-P., Fridovich-Keil, J. L., and Pardee, A. B. (1991) Proc. Natl. Acad. Sci. U. S. A. 88,1157-1161). Here we report that MT2 includes an E2F-like binding site (GTTCGCGGGCAAA), as shown by the following evidence. (i) Mt2 bound specifically to an affinity-purified fusion human E2F protein. (ii) Both MT2 and an authentic E2F site (TTTCGCGCGCTTT) bound specifically to similar or identical nuclear protein complexes. (iii) Formation of both these DNA-protein complexes were cell cycle-dependent: a G0/G1 phase-specific complex (E2F.G0/G1) was replaced by an S phase-specific complex(es) (E2F.S), whereas ''free'' E2F increased after the G1/S transition. (iv) Pulse inhibition of protein synthesis with cycloheximide interchanged these complexes with similar kinetics. (v) When MT2-shifted E2F.G0/Gl, E2F.S, and free E2F were eluted and analyzed by Western blot assay using a specific antiserum to human E2F-1, two forms of murine E2F (62 and 66 kDa) were observed from all three complexes. The compositions of these MT2-bound complexes were also investigated. Studies using specific antibodies revealed that p107, a retinoblastoma-like protein, was present in both E2F.G0/G1 and E2F.S, whereas cyclin E.cyclin A.cdk2 were only present in E2F.S complex(es). These data suggest that removal of the p107-containing E2F.G0/Gl complex, a candidate repressor, from the MT2 site in late G1 may be essential for S phase-dependent transcription of the mouse TK gene. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. FU NCI NIH HHS [CA22427]; NCRR NIH HHS [2 S07RR05526-28]; NIGMS NIH HHS [GM24571] NR 49 TC 89 Z9 89 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 14 PY 1994 VL 269 IS 2 BP 1306 EP 1313 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR220 UT WOS:A1994MR22000085 PM 8288595 ER PT J AU NASH, IS FALLON, JT DINSMORE, RE GILBERT, J AF NASH, IS FALLON, JT DINSMORE, RE GILBERT, J TI A 31-YEAR-OLD MAN WITH A PREVIOUS PERICARDIECTOMY FOR CONSTRICTIVE PERICARDITIS AND MITRAL REGURGITATION - CONSTRICTIVE PERICARDITIS, IDIOPATHIC, RECURRENT - MYOCARDIAL AND ENDOCARDIAL FIBROSIS INVOLVING PAPILLARY-MUSCLE, PROBABLY ISCHEMIC - MYXOMATOUS CHANGE OF MITRAL-VALVE (WITH MITRAL REGURGITATION) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID RESTRICTIVE CARDIOMYOPATHY; CARDIAC-TAMPONADE; CHORDAL RUPTURE; ETIOLOGY; EPICARDITIS; SPECTRUM; PROLAPSE; SURGERY C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP NASH, IS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 47 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 JAN 13 PY 1994 VL 330 IS 2 BP 126 EP 134 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA MQ670 UT WOS:A1994MQ67000009 ER PT J AU COHEN, LS FRIEDMAN, JM JEFFERSON, JW JOHNSON, EM WEINER, ML AF COHEN, LS FRIEDMAN, JM JEFFERSON, JW JOHNSON, EM WEINER, ML TI A REEVALUATION OF RISK OF IN-UTERO EXPOSURE TO LITHIUM SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID TERATOGEN UPDATE; PREGNANCY; PHENOTHIAZINES; MALFORMATIONS; WOMEN; MANIA AB Objective.-To reevaluate the risk associated with in utero exposure to lithium. Data Sources and Study Selection.-Data were obtained from all published studies, in multiple languages, referenced in MEDLINE, Toxline, and the Lithium Information Center databases. Unpublished studies were not included. The search terms were lithium, pregnancy, teratogen, abnormalities (drug induced), Ebstein's anomaly, and adverse effects. Data Extraction and Synthesis.-In the 1970s a very strong association was suggested between maternal lithium treatment during pregnancy and Ebstein's anomaly of the heart in the offspring. The relative risk for Ebstein's anomaly among such children was estimated to be 400 on the basis of data collected from a registry of voluntarily submitted cases. More recent controlled epidemiologic studies have consistently shown a lower risk. No women who took lithium during pregnancy were found among four case-control studies of Ebstein's anomaly involving 25, 34, 59, and 89 affected children, respectively. In two cohort studies, risk ratios of 3.0 (95% confidence interval [CI], 1.2 to.7.7) and 1.5 (95% CI, 0.4 to 6.8) for all congenital anomalies have been observed. The risk ratios for cardiac malformations in these studies were 7.7 (95% CI 1.5 to 41.2) and 1.2 (95% CI, 0.1 to 18.3), respectively. Conclusion.-While initial information regarding the teratogenic risk of lithium treatment was derived from biased retrospective reports, more recent epidemiologic data indicate that the teratogenic risk of first-trimester lithium exposure is lower than previously suggested. The clinical management of women with bipolar disorder who have childbearing potential should be modified with this revised risk estimate. C1 UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER V6T 1W5,BC,CANADA. DEAN FDN HLTH RES & EDUC,CTR LITHIUM INFORMAT,MADISON,WI. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DANIEL BAUGH INST,DEPT ANAT,PHILADELPHIA,PA 19107. FMC CORP,DEPT TOXICOL,PRINCETON,NJ. RP COHEN, LS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. RI Kothari, Khyati/B-5008-2014 FU NIMH NIH HHS [MH-19445] NR 49 TC 248 Z9 251 U1 4 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 12 PY 1994 VL 271 IS 2 BP 146 EP 150 DI 10.1001/jama.271.2.146 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA MQ083 UT WOS:A1994MQ08300026 PM 8031346 ER PT J AU SUHL, J SIMONS, P REEDY, T GARRICK, T AF SUHL, J SIMONS, P REEDY, T GARRICK, T TI MYTH OF SUBSTITUTED JUDGMENT - SURROGATE DECISION-MAKING REGARDING LIFE-SUPPORT IS UNRELIABLE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PROXY AB Objective: To identify factors predicting the accuracy of surrogate decision making in life support decisions. Design: Questionnaire. Setting: Urban Veterans Affairs hospital. Patients and Design: Fifty hospitalized patients and their chosen surrogates were given questionnaires describing life support modalities and four common medical scenarios in which life support would be contemplated. An additional 50 patients also completed the questionnaire. Patients gave their choices of life support in the different scenarios. Surrogates guessed the patients' answers (substituted judgment). Details of the patient-surrogate relationship were asked. Patients completed a depression inventory. Main Outcome Measure: Patient-surrogate agreement. Main Results: Surrogates correctly guessed patients' wishes about life support overall on 59.3% of the questions, not better than random chance (kappa=.09). The only predictor of accurate surrogate decision making was specific discussion between patient and surrogate about life support. Secondary Results: Patients had an overall low desire for life support (35%), and a majority favored euthanasia under some circumstances (62%). There was no relationship between depression score and desire for life support. Conclusions: Substituted judgment by surrogates is not more accurate than random chance. Discussion between patient and surrogate about life support correlated with more accurate substituted judgment. C1 W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PSYCHIAT, LOS ANGELES, CA USA. NR 16 TC 144 Z9 144 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 10 PY 1994 VL 154 IS 1 BP 90 EP 96 DI 10.1001/archinte.154.1.90 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA MQ203 UT WOS:A1994MQ20300011 PM 8267493 ER PT J AU SPECTOR, NL MEHLEN, P RYAN, C HARDY, L SAMSON, W LEVINE, H NADLER, LM FABRE, N ARRIGO, AP AF SPECTOR, NL MEHLEN, P RYAN, C HARDY, L SAMSON, W LEVINE, H NADLER, LM FABRE, N ARRIGO, AP TI REGULATION OF THE 28 KDA HEAT-SHOCK PROTEIN BY RETINOIC ACID DURING DIFFERENTIATION OF HUMAN LEUKEMIC HL-60 CELLS SO FEBS LETTERS LA English DT Article DE HEAT SHOCK PROTEIN; PHOSPHORYLATION; RETINOIC ACID; HL-60; DIFFERENTIATION ID ACUTE PROMYELOCYTIC LEUKEMIA; DROSOPHILA DEVELOPMENT; GROWTH ARREST; EXPRESSION; PHOSPHORYLATION; HSP27; LOCALIZATION; INDUCTION; THERAPY; GENES AB Dysregulation of hematopoietic cellular differentiation contributes to leukemogenesis. Unfortunately relatively little is known about how cell differentiation is regulated. Considering that heat shock proteins (hsp) and specifically the small hsps have been increasingly linked to growth regulation, we sought to determine whether the mammalian small hsp (hsp28) is a growth-regulatory candidate during hematopoietic cell differentiation. Because of its effects on cell growth and differentiation and its increasing clinical use as a differentiating agent, we examined the effect of retinoic acid (RA) on hsp28 during differentiation of the human leukemic HL-60 cell line. Although hsp28 was constitutively expressed at low levels in untreated HL-60 cells, steady state hsp28 protein increased transiently, concomitant with the onset of G1 cell cycle arrest. Furthermore, hsp28 phosphorylation transiently increased within one hour following treatment with RA. Interestingly, in contrast to other differentiating agents the induction of hsp28 by RA was post-transcriptionally mediated with hsp28 protein and mRNA being discordantly regulated. These observations underscore the complex regulation of hsp28 by RA during granulocytic differentiation of human leukemic cells and indicate hsp28 as an intermediary in the pathway through which retinoids exert their growth and differentiative effects. C1 UNIV LYON 1,CTR GENET MOLEC,STRESS CELLULAIRE LAB,CNRS,UMR 106,F-69628 VILLEURBANNE,FRANCE. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV MIAMI,SCH MED,DIV HEMATOL ONCOL,MIAMI,FL 33136. FU NCI NIH HHS [CA-40216-06, IF32CA08954-01] NR 32 TC 45 Z9 45 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 JAN 10 PY 1994 VL 337 IS 2 BP 184 EP 188 DI 10.1016/0014-5793(94)80270-X PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA MR464 UT WOS:A1994MR46400014 PM 8287974 ER PT J AU WHITE, MF KAHN, CR AF WHITE, MF KAHN, CR TI THE INSULIN SIGNALING SYSTEM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID KINASE DOMAIN AUTOPHOSPHORYLATION; RECEPTOR KINASE; TYROSINE KINASE; PHOSPHATIDYLINOSITOL 3'-KINASE; TRANSMEMBRANE DOMAIN; LIGAND-BINDING; PROTEIN; IRS-1; PHOSPHORYLATION; ACTIVATION C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP WHITE, MF (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK33201, DK38712, DK43808] NR 67 TC 1274 Z9 1291 U1 2 U2 44 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 1 EP 4 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900001 PM 8276779 ER PT J AU VANHORN, DJ MYERS, MG BACKER, JM AF VANHORN, DJ MYERS, MG BACKER, JM TI DIRECT ACTIVATION OF THE PHOSPHATIDYLINOSITOL 3'-KINASE BY THE INSULIN-RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID RAT HEPATOMA-CELLS; TYROSINE KINASE; 3-KINASE ACTIVITY; SIGNAL TRANSMISSION; GROWTH-FACTOR; INTACT RAT; PHOSPHORYLATION; EXPRESSION; IRS-1; STIMULATION AB We have previously shown that phosphatidylinositol (PtdIns) 3'-kinase is activated by the binding of proteins or peptides containing the phosphorylated motif Y(P)XXM. In the present study, we examine interactions between PtdIns 3'-kinase and the human insulin receptor, which contains a C-terminal phosphorylation site in the sequence Y1322THM. Partially purified insulin receptors bound tightly to bacterial fusion proteins containing the N- or C-terminal SH2 domains from PtdIns 3'-kinase regulatory subunit (p85). In contrast, a mutant insulin receptor, truncated by 43 amino acids at the C terminus (IR(DELTACT)), bound poorly to the SH2 domains; these mutant receptors have normal kinase activity but lack the Y1322THM motif. Similarly, incubation with wild-type receptors increased the activity of immunopurified PtdIns 3'-kinase, whereas incubation with IR(DELTACT) receptors did not affect PtdIns 3'-kinase activity. Activation of PtdIns 3'-kinase by the wild-type receptor was mimicked by a tyrosyl phosphopeptide derived from the insulin receptor C terminus and containing the Y1322THM motif; non-phosphorylated peptide did not affect activity. Thus, the insulin receptor C terminus activates PtdIns 3'-kinase in vitro by binding to the SH2 domains of the 85-kDa regulatory subunit. These data support the hypothesis that binding of tyrosyl-phosphorylated receptors to p85 SH2 domains is a general mechanism for PtdIns 3'-kinase activation, and they suggest that direct interactions between the insulin receptor and PtdIns 3'-kinase may provide an alternative pathway for the activation of this enzyme by insulin. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MOLEC PHARMACOL,1300 MORRIS PK AVE,BRONX,NY 10461. BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DEPT MED,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK-44541] NR 36 TC 107 Z9 111 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 7 PY 1994 VL 269 IS 1 BP 29 EP 32 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900008 PM 8276809 ER PT J AU YENUSH, L KUNDRA, V WHITE, MF ZETTER, BR AF YENUSH, L KUNDRA, V WHITE, MF ZETTER, BR TI FUNCTIONAL DOMAINS OF THE INSULIN-RECEPTOR RESPONSIBLE FOR CHEMOTACTIC SIGNALING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOGENOUS SUBSTRATE PHOSPHORYLATION; HUMAN INTERLEUKIN-8 RECEPTOR; TYROSINE KINASE-ACTIVITY; BC3H-1 MURINE MYOCYTES; GROWTH-FACTOR; JUXTAMEMBRANE REGION; BETA-SUBUNIT; PROTEIN; CELLS; AUTOPHOSPHORYLATION AB The insulin receptor mediates a variety of cellular responses to insulin, including glucose transport, endocytosis, and cell proliferation. The role of the insulin receptor in mediating cellular motility has not, however, been extensively investigated. In this report, we demonstrate that chinese hamster ovary (CHO) cells that normally have low concentrations of insulin receptor display chemotaxis toward insulin after overexpression of the wild type human insulin receptor. Chemotaxis toward insulin proceeded through a pertussis toxin-sensitive pathway and required both tyrosine kinase activity and tyrosine autophosphorylation of the regulatory region of the beta-subunit. In contrast, the autophosphorylation sites in the carboxyl terminus of the receptor were not required for chemotactic activity. A mutation in the juxtamembrane region, which disabled tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), also prevented the chemotactic response, suggesting a possible role for IRS-1 in chemotactic signaling. In the absence of insulin receptor, however, the presence of excess transfected IRS-1 was not sufficient to mediate chemotaxis toward insulin. These results demonstrate that the intact insulin receptor can stimulate a chemotactic signaling pathway and that this initial pathway more closely correlates with that for insulin-stimulated cell proliferation than for insulin-stimulated receptor endocytosis. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,300 LONGWOOD AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02115. JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK 38712, DK 43808] NR 33 TC 23 Z9 23 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 JAN 7 PY 1994 VL 269 IS 1 BP 100 EP 104 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA MR219 UT WOS:A1994MR21900023 PM 8276780 ER EF