FN Thomson Reuters Web of Science™ VR 1.0 PT S AU TALAL, N AF TALAL, N BE Bystryn, JC Ferrone, S Livingston, P TI LESSONS FROM AUTOIMMUNITY SO SPECIFIC IMMUNOTHERAPY OF CANCER WITH VACCINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON SPECIFIC IMMUNOTHERAPY OF CANCER WITH VACCINES CY JAN 21-24, 1993 CL WASHINGTON, DC SP NEW YORK ACAD SCI, NCI, BIOMIRA INC, CAMBRIDGE BIOTECH, AMER CYANAMID, BRISTOL MYERS SQUIBB, PHARM RES INST, CYTOGEN CORP, GENENTECH, GENETICS INST, HOFFMANN LA ROCHE RP TALAL, N (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CLIN IMMUNOL SECT,SAN ANTONIO,TX 78284, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK SN 0077-8923 BN 0-89766-825-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1993 VL 690 BP 19 EP 23 PG 5 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA BY95C UT WOS:A1993BY95C00004 ER PT B AU HISNANICK, JJ AF HISNANICK, JJ GP SAS USERS GRP INT TI USING SAS ETS IN APPLIED ECONOMETRICS - PARAMETERS ESTIMATES FOR THE CES-TRANSLOG SPECIFICATION SO SUGI 18: PROCEEDINGS OF THE EIGHTEENTH ANNUAL SAS USERS GROUP INTERNATIONAL CONFERENCE LA English DT Proceedings Paper CT 18th Annual SAS Users Group International Conference (SUGI 18) CY MAY 09-12, 1993 CL NEW YORK, NY SP SAS USERS GRP INT C1 US DEPT VET AFFAIRS,NATL CTR VET ANAL & STAT,WASHINGTON,DC 20420. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAS INST INC PI CARY PA SAS CIRCLE, PO BOX 8000, CARY, NC 27511 BN 1-55544-550-0 PY 1993 BP 275 EP 279 PG 5 WC Computer Science, Information Systems; Computer Science, Software Engineering SC Computer Science GA BA72C UT WOS:A1993BA72C00045 ER PT J AU RYAN, CM CARTER, EA JENKINS, RL STERLING, LM YARMUSH, ML MALT, RA TOMPKINS, RG AF RYAN, CM CARTER, EA JENKINS, RL STERLING, LM YARMUSH, ML MALT, RA TOMPKINS, RG TI ISOLATION AND LONG-TERM CULTURE OF HUMAN HEPATOCYTES SO SURGERY LA English DT Article ID ADULT HUMAN HEPATOCYTES; HEPATITIS-B VIRUS; LIVER BIOPSIES; RAT; TRANSPLANTATION; METABOLISM; SECRETION; CELLS AB Pressure-controlled perfusion of specimens of surgical hepatic resection produced improved yields of human hepatocytes for studies of long-term cultures. The effect of an extracellular matrix configuration on albumin secretion was evaluated by culture on a single layer of collagen or between double layers of collagen gel with Dulbecco's modified Eagle and Williams E media. Hepatocytes from 12 patients were maintained for more than 30 days, and in five of 12 experiments cells were cultured beyond 2 months. In the double gels the cells demonstrated typical polygonal liver cell morphology and higher albumin secretion (p < 0.01) up to 65 days; in contrast, in the single gels cells spread horizontally, and albumin secretion declined rapidly within 3 weeks. A comparison of media formulations showed that maximum albumin secretion occurred 5 days later but was maintained significantly longer with Dulbecco's medium (p < 0.01). The simple addition of a second layer of gelled collagen forming a collagen sandwich significantly stabilizes and supports the long-term culture of human hepatocytes. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BIGELOW 1302,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,CHILDRENS SERV,BOSTON,MA 02114. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02215. FU NIDDK NIH HHS [DK 41709, DK 01746]; NIGMS NIH HHS [GM 21700] NR 32 TC 53 Z9 58 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD JAN PY 1993 VL 113 IS 1 BP 48 EP 54 PG 7 WC Surgery SC Surgery GA KF149 UT WOS:A1993KF14900008 PM 8417488 ER PT J AU WILLETT, CG WARSHAW, AL CONVERY, K COMPTON, CC AF WILLETT, CG WARSHAW, AL CONVERY, K COMPTON, CC TI PATTERNS OF FAILURE AFTER PANCREATICODUODENECTOMY FOR AMPULLARY CARCINOMA SO SURGERY GYNECOLOGY & OBSTETRICS LA English DT Article ID PANCREATIC-CANCER; VATER; SURVIVAL; ADENOCARCINOMA; MORBIDITY; MORTALITY; RESECTION AB The clinical courses of 41 patients with ampullary carcinoma were retrospectively reviewed to determine patterns of failure after resection. The five year actuarial local control and overall survival rates of 29 patients undergoing only pancreaticoduodenectomy were 69 and 55 percent, respectively. For 12 patients with ''low risk'' pathologic features (tumors limited to the ampulla or duodenum, well or moderately well-differentiated histologic factors, uninvolved lymph nodes or resection margins), the five year actuarial local control and survival rate was 100 and 80 percent, respectively. Adjuvant treatment may be unnecessary for this favorable subset of patients. On the other hand, the five year actuarial local control and survival after pancreaticoduodenectomy of 17 patients with ''high risk'' pathologic features (tumors invasive of the pancreas, poorly differentiated histologic findings, involved lymph nodes or resection margins) was only 50 and 38 percent, respectively (p<0.05). In 12 patients at ''high risk'' who also received postoperative radiation therapy after pancreaticoduodenectomy, there was a trend toward better local control (83 percent), but there was no improvement in survival. Distant metastases (liver, peritoneum and pleura) were the dominant factor in determining outcome in this group. Therefore, we propose a trial of preoperative irradiation in hopes of enhancing these outcomes by reducing the risk of dissemination of cancer cells during surgical resection, especially among the 70 percent of patients with high risk pathologic features. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG & PATHOL,BOSTON,MA 02114. RP WILLETT, CG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,50 BLOSSOM ST,BOSTON,MA 02114, USA. NR 20 TC 80 Z9 81 U1 0 U2 1 PU FRANKLIN H MARTIN FOUNDATION PI CHICAGO PA 55 E ERIE ST, CHICAGO, IL 60611 SN 0039-6087 J9 SURG GYNECOL OBSTET JI Surg. Gynecol. Obstet. PD JAN PY 1993 VL 176 IS 1 BP 33 EP 38 PG 6 WC Obstetrics & Gynecology; Surgery SC Obstetrics & Gynecology; Surgery GA KF804 UT WOS:A1993KF80400006 PM 8093983 ER PT J AU FERNANDEZDELCASTILLO, C WARSHAW, AL AF FERNANDEZDELCASTILLO, C WARSHAW, AL TI LAPAROSCOPY FOR STAGING IN PANCREATIC-CARCINOMA SO SURGICAL ONCOLOGY-OXFORD LA English DT Article DE LAPAROSCOPY; PANCREATIC CANCER; PERITONEAL METASTASES AB Pancreatic cancer is the gastrointestinal malignancy with the worst prognosis. At the time of diagnosis, only 15% of patients are resectable (and potentially curable), 40% have localized but unresectable tumours, and 45% distant metastases. Computerized tomography, angiography, and laparoscopy allow for adequate staging in this neoplasm. The latter is useful for identifying the small (1-2 mm) peritoneal and liver implants which, in our experience, are present in 27% of patients with tumours of the pancreatic head and in 65% of those with cancers of the body and tail of the pancreas. Peritoneal cytology may also be performed at the time of laparoscopy, and will be positive for malignant cells in 20-30% of cases indicating a bad prognosis. C1 MASSACHUSETTS GEN HOSP,ACC-336,BOSTON,MA 02114. NR 0 TC 23 Z9 24 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0960-7404 J9 SURG ONCOL JI Surg. Oncol.-Oxf. PY 1993 VL 2 SU 1 BP 25 EP 29 PG 5 WC Oncology; Surgery SC Oncology; Surgery GA MH350 UT WOS:A1993MH35000005 PM 8252218 ER PT S AU HODGSON, JM JOHNSON, G AF HODGSON, JM JOHNSON, G BE Tallal, P Galaburda, AM Llinas, RR Voneuler, C TI VISUAL WORD RECOGNITION IN DEVELOPMENTAL DYSGRAPHIA - ONE LEXICON OR 2 SO TEMPORAL INFORMATION PROCESSING IN THE NERVOUS SYSTEM: SPECIAL REFERENCE TO DYSLEXIA AND DYSPHASIA SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Proceedings Paper CT CONF ON TEMPORAL INFORMATION PROCESSING IN THE NERVOUS SYSTEM : SPECIAL REFERENCE TO DYSLEXIA AND DYSPHASIA CY SEP 12-15, 1992 CL NEW YORK, NY SP RODIN REMEDIAT ACAD, NEW YORK ACAD SCI, NICHD, NIDOCD, NINDS, HOECHST ROUSSEL PHARM, RITA RUDEL FDN RP HODGSON, JM (reprint author), MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,GRAD PROGRAM COMMUN SCI & DISORDERS,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA NEW YORK SN 0077-8923 BN 0-89766-785-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1993 VL 682 BP 354 EP 356 DI 10.1111/j.1749-6632.1993.tb22992.x PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BY50H UT WOS:A1993BY50H00039 PM 8323134 ER PT J AU GOLDEN, JA CHERNOFF, GF AF GOLDEN, JA CHERNOFF, GF TI INTERMITTENT PATTERN OF NEURAL-TUBE CLOSURE IN 2 STRAINS OF MICE SO TERATOLOGY LA English DT Article ID RETINOIC ACID; MOUSE EMBRYO; NEURULATION; BRAIN AB Development of the neural tube is often described as a continuous process that begins in the cervical region of the embryo and proceeds both rostrally and caudally. Examination of neural tube closure in the cranial region of LM/Bc and SWV/Bc mice revealed an intermittent pattern with four distinct areas of closure. Closure I begins at the level of somites 1-3 and proceeds bidirectionally. Closure II is initiated at the prosencephalic-mesencephalic border and also proceeds bidirectionally. Closure III is unidirectional, beginning adjacent to the stomodeum and proceeding caudally to meet closure II. Finally, closure IV takes place over the rhombencephalon where it meets closure II to complete rostral neural tube closure. In these two strains of mice anterior neural tube closure progressed as somite number increased. However, the SWV strain required a longer gestational time to develop equal numbers of somites and therefore to complete closure. In light of the intermittent pattern of closure observed in mice, the development of the rostral nervous system in other mammals, including humans, should be reconsidered. C1 CALIF ENVIRONM PROTECT AGCY,SACRAMENTO,CA 94234. UNIV CALIF SAN DIEGO,SCH MED,DEPT PEDIAT,LA JOLLA,CA 92093. RP GOLDEN, JA (reprint author), MASSACHUSETTS GEN HOSP,CHARLES S KUBIK LAB NEUROPATHOL,DEPT PATHOL,WARREN 3,BOSTON,MA 02114, USA. NR 37 TC 75 Z9 80 U1 0 U2 3 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 JAN PY 1993 VL 47 IS 1 BP 73 EP 80 DI 10.1002/tera.1420470112 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA KK386 UT WOS:A1993KK38600011 PM 8475460 ER PT J AU SANDERS, KM CASSEM, EH AF SANDERS, KM CASSEM, EH TI PSYCHIATRIC COMPLICATIONS IN THE CRITICALLY ILL CARDIAC PATIENT SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article DE ANXIETY; BEHAVIORAL DISTURBANCES; BENZODIAZEPINES; CORONARY DISEASE; CORONARY CARE UNITS; DELIRIUM; HALOPERIDOL INFUSIONS, INTRAVENOUS; INTRAAORTIC BALLOON PUMP; ORGANIC MENTAL DISORDERS; PSYCHOMOTOR AGITATION AB Psychiatric consultation to the critically ill cardiac patient focuses on several common problems: anxiety, delirium, depression, personality reactions, and behavioral disturbances. A review of the causes and treatment of anxiety in the coronary care unit is followed by a discussion of delirium in the critically ill cardiac patient. A description of delirium associated with the use of the intraaortic balloon pump and its treatment with high doses of intravenous haloperidol is also included. After the initial crisis has been stabilized in the critical care unit, the premorbid personality traits of the patient may emerge as behavioral disturbances-particularly as the duration of stay increases. The use of psychiatric consultation completes the discussion. RP SANDERS, KM (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 16 Z9 16 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 SN 0730-2347 J9 TEX HEART I J JI Tex. Heart Inst. J. PY 1993 VL 20 IS 3 BP 180 EP 187 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LY706 UT WOS:A1993LY70600006 PM 8219821 ER PT J AU YUNIS, JJ SALAZAR, M DELGADO, MB ALPER, CA BING, DH YUNIS, EJ AF YUNIS, JJ SALAZAR, M DELGADO, MB ALPER, CA BING, DH YUNIS, EJ TI HLA-DQA1, DQB1 AND DPB1 ALLELES ON HLA-DQ2-CARRYING AND DQ9-CARRYING EXTENDED HAPLOTYPES SO TISSUE ANTIGENS LA English DT Article DE MHC, CLASS-II, DQ2, DQA1, DQB1, DPB1 ALLELES; EXTENDED HAPLOTYPES ID MAJOR HISTOCOMPATIBILITY COMPLEX; ENZYMATIC AMPLIFICATION; OLIGONUCLEOTIDE PROBES; DNA; POPULATIONS; POLYMERASE AB DQA1, DQB1 and DPB1 alleles were investigated in a large panel of samples carrying HLA-DQ2- and HLA-DQ9-bearing extended haplotypes. Every instance of the [HLA-B8, SCO1, DR3, DQ2a] and [HLA-B18, F1C30, DR3, DQ2b] extended haplotypes carried the DQA1*0501 allele, while every instance of [HLA-B44, FC31, DR7, DQ2c], [HLA-B47, FC91,0, DR7, DQ2c] and [HLA-B57, SC61, DR7, DQ2d] carried the DQA1*0201 allele. All HLA-DR3, DQ2 and HLA-DR7, DQ2 extended haplotypes carried the DQB1*0201 allele. Every example of [HLA-B57, SC61, DR7, DQ9] carried the DQB1*0303 allele. Several associations between the DPB1 alleles and some HLA-DQ2- and DQ9-carrying extended haplotypes were identified. HLA-DPw2-encoding alleles, DPB1*0202 (50%, p<0.001) and 0201 (30%), were found on the [HLA-B18, F1C30, DR3, DQ2b] extended haplotype. Every instance of the [HLA-B57, SC6], DR7, DQ9] extended haplotype carried the DPB1*0401 allele. Also, we have confirmed the associations of the DPB1*0101 and DPB1*0401 alleles with the [HLA-B8, SC01, DR3, DQ2a] extended haplotype. The analysis of homozygous typing cells carrying the [HLA-B44, FC31, DR7, DQ2c] extended haplotype showed that the DPB1*0401 and 0201 alleles were present at similar frequencies (37.5%), while the DPB1*1101 allele was found in only 25% of these haplotypes analyzed. Our results suggest that the constancy of the DNA of the HLA-B, DR, DQ regions may extend to the DP region and that the extent of such fixity varies, perhaps as the result of ethnic variability of the population studied. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP YUNIS, JJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV IMMUNOGENET,DANA 740,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA20531]; NIAID NIH HHS [AI14157]; NIDDK NIH HHS [DK26844] NR 22 TC 17 Z9 17 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JAN PY 1993 VL 41 IS 1 BP 37 EP 41 DI 10.1111/j.1399-0039.1993.tb01975.x PG 5 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA KL167 UT WOS:A1993KL16700006 PM 8096094 ER PT B AU TONER, M TOMPKINS, RG YARMUSH, ML AF TONER, M TOMPKINS, RG YARMUSH, ML BE Bell, E TI LIVER SUPPORT THROUGH HEPATIC TISSUE ENGINEERING SO TISSUE ENGINEERING: CURRENT PERSPECTIVES LA English DT Proceedings Paper CT Tissue Engineering Meeting CY 1992 CL KEYSTONE, CO SP KEYSTONE ORG, GENETECH INC, KEYSTONE SYMP MOLEC & CELLULAR BIOL C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIRKHAUSER BOSTON PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139-2333 BN 0-8176-3687-0 PY 1993 BP 92 EP 107 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BZ63F UT WOS:A1993BZ63F00009 ER PT J AU ARATEN, DJ LAWTON, T FERRARA, J ANTIN, JH MILFORD, E CARPENTER, CB MAZIARZ, RT AF ARATEN, DJ LAWTON, T FERRARA, J ANTIN, JH MILFORD, E CARPENTER, CB MAZIARZ, RT TI INVITRO ALLOREACTIVITY AGAINST HOST ANTIGENS IN AN ADULT HLA-MISMATCHED BONE-MARROW TRANSPLANT RECIPIENT DESPITE INVIVO HOST TOLERANCE SO TRANSPLANTATION LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; SEVERE COMBINED IMMUNODEFICIENCY; T-CELL CLONES; SELF-TOLERANCE; CLASS-I; ANTIIDIOTYPIC ANTIBODIES; TRANSGENIC MICE; DONOR-TYPE; B-CELLS; THYMUS AB An adult recipient of an HLA-DR, DQ-mismatched, T cell-depleted bone marrow graft, who remains without graft versus host disease and who is not maintained on immunosuppressive therapy, was studied at 23 months posttransplantation for in vitro reactivity against the mismatched antigens of the host. The donor's PBMC's proliferated vigorously against the recipient's stimulators in the pretransplant mixed lymphocyte cultures (MLC). After transplant reconstitution, MLCs demonstrated that the in vitro response of engrafted donor T cells against host MHC class II antigens was equivalent to control allogeneic responses, while there was no detectable response against the donor's antigens. Posttransplantation limiting dilution analysis showed no difference between the precursor frequencies of antihost responders among populations of fresh donor PBMCs and among the engrafted cells of donor origin that are found circulating in the patient. This result suggests that clonal deletion is, at best, incomplete and that peripheral tolerance is essential in protecting this patient from GVHD. These findings also support the conclusion that bone marrow-derived thymic elements may be important for clonal deletion in human chimeras. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV HEMATOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NCI NIH HHS [CA 39542]; NIAID NIH HHS [P01 AI-23360] NR 53 TC 6 Z9 6 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN PY 1993 VL 55 IS 1 BP 76 EP 82 DI 10.1097/00007890-199301000-00015 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA KH660 UT WOS:A1993KH66000015 PM 8420068 ER PT J AU SYKES, M SACHS, DH NIENHUIS, AW PEARSON, DA MOULTON, AD BODINE, DM AF SYKES, M SACHS, DH NIENHUIS, AW PEARSON, DA MOULTON, AD BODINE, DM TI SPECIFIC PROLONGATION OF SKIN-GRAFT SURVIVAL FOLLOWING RETROVIRAL TRANSDUCTION OF BONE-MARROW WITH AN ALLOGENEIC MAJOR HISTOCOMPATIBILITY COMPLEX GENE SO TRANSPLANTATION LA English DT Note ID CLASS-II GENE; HEMATOPOIETIC-CELLS; MONOCLONAL-ANTIBODIES; STEM-CELLS; EXPRESSION; TOLERANCE; MICE; TRANSPLANTS; REJECTION; LEUKEMIA AB Engrafted allogeneic hematopoietic cells have a unique capacity to induce a state of donor-specific transplantation tolerance across major histocompatibility complex barriers. This state allows permanent acceptance of donor-type organ grafts, with otherwise normal immunocompetence. We hypothesized that introduction of allogeneic MHC genes into autologous bone marrow which is then returned to recipient mice might similarly induce specific tolerance to products of the introduced MHC genes, without the risk of graft-vs-host disease. We demonstrate here that the introduction of MHC class I K(b) cDNA by retrovirus-mediated gene transfer into B10.AKM (K(k)) hematopoietic cells confers specific hyporesponsiveness to allogeneic skin grafts expressing K(b). C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. RP SYKES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT BIOL RES CTR,13TH ST,MGH E,BOSTON,MA 02114, USA. FU PHS HHS [N01-H1-19054] NR 35 TC 111 Z9 111 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN PY 1993 VL 55 IS 1 BP 197 EP 202 DI 10.1097/00007890-199301000-00037 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA KH660 UT WOS:A1993KH66000037 PM 8420048 ER PT J AU SASAKI, AW LEE, RG PORAYKO, MK BENNER, KG HENNELL, KR WHEELER, LJ PINSON, CW AF SASAKI, AW LEE, RG PORAYKO, MK BENNER, KG HENNELL, KR WHEELER, LJ PINSON, CW TI ACCELERATED LIVER ALLOGRAFT-REJECTION DURING PROPHYLACTIC IMMUNOSUPPRESSION WITH OKT3 SO TRANSPLANTATION LA English DT Note ID RANDOMIZED CLINICAL-TRIAL; MONOCLONAL-ANTIBODY; TRANSPLANTATION; EXPERIENCE; RECIPIENTS; THERAPY C1 OREGON HLTH SCI UNIV,DEPT CLIN TRANSPLANT,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT PATHOL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT MED,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,IMMUNOGENET & TRANSPLANT LAB,PORTLAND,OR 97201. PORTLAND VA MED CTR,PORTLAND,OR. VANDERBILT UNIV,DEPT ORAL HLTH RES,NASHVILLE,TN 37240. VANDERBILT UNIV,DEPT SURG,NASHVILLE,TN 37240. NR 15 TC 3 Z9 3 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 JAN PY 1993 VL 55 IS 1 BP 216 EP 219 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA KH660 UT WOS:A1993KH66000044 PM 8420054 ER PT J AU SWEADNER, KJ AF SWEADNER, KJ TI MULTIPLE DIGITALIS RECEPTORS - A MOLECULAR PERSPECTIVE SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID NA,K-ATPASE ALPHA-SUBUNIT; OUABAIN BINDING-SITES; ENZYMATIC-PROPERTIES; CARDIAC-GLYCOSIDES; BETA-SUBUNIT; HUMAN-HEART; HUMAN-BRAIN; RAT; EXPRESSION; ATPASE AB The Na, K-ATPase is the only established receptor for cardiac glycosides isoforms of its principal subunit. These isoforms can differ from one another in their intrinsic affinity for cardiac glycosides. Recent work examines the molecular structure of the binding site. The relative level of expression of the isoforms in cardiac tissue is modified in several developmental, hormonal, and pathological states, contributing to alterations in the digitalis sensitivity of the tissue. C1 HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02114. RP SWEADNER, KJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 44 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JAN-FEB PY 1993 VL 3 IS 1 BP 2 EP 6 DI 10.1016/1050-1738(93)90020-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KL382 UT WOS:A1993KL38200002 PM 21244963 ER PT J AU DOUKAS, AG MCAULIFFE, DJ FLOTTE, TJ AF DOUKAS, AG MCAULIFFE, DJ FLOTTE, TJ TI BIOLOGICAL EFFECTS OF LASER-INDUCED SHOCK-WAVES - STRUCTURAL AND FUNCTIONAL CELL-DAMAGE INVITRO SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE ULTRASONICS; SHOCK WAVES; CELL VIABILITY; ELECTRON MICROSCOPY; THYMIDINE INCORPORATION; CELL DAMAGE; LASERS; CAVITATION ID OPTICAL-BREAKDOWN; HIGH-INTENSITY; CAVITATION; TISSUE; DNA; LITHOTRIPTER; L1210-CELLS; ULTRASOUND; RADIATION; REDUCTION AB A new experimental design has been used to study the biological effects of laser-induced shock waves which minimizes or eliminates interference from ancillary effects such as bubble formation, ultraviolet (UV) radiation, or formation of radicals. The effects of these shock waves on human lymphocytes and red blood cells have been investigated. Three assays were used to determine cell injury: electron microscopy, ethidium bromide/fluorescein diacetate (EB/FDA) staining and incorporation of tritiated thymidine. The degree of cell damage was related to the pressure and the number of pulses. Cell damage was quantified and correlated using the three assays. Measurements of gross structural alterations as determined by transmission electron microscopy were less sensitive than assays of structural damage (e.g., EB/FDA assay) which were less sensitive than functional assays (e.g., incorporation of tritiated thymidine). C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. RP DOUKAS, AG (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. NR 45 TC 72 Z9 72 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PY 1993 VL 19 IS 2 BP 137 EP 146 DI 10.1016/0301-5629(93)90006-A PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA KV861 UT WOS:A1993KV86100006 PM 8516960 ER PT J AU MILLER, SI LOOMIS, WP ALPUCHEARANDA, C BEHLAU, I HOHMANN, E AF MILLER, SI LOOMIS, WP ALPUCHEARANDA, C BEHLAU, I HOHMANN, E TI THE PHOP VIRULENCE REGULON AND LIVE ORAL SALMONELLA VACCINES SO VACCINE LA English DT Article; Proceedings Paper CT INTERNATIONAL CONF ON VACCINES FOR ENTERIC DISEASES CY APR 13-15, 1992 CL ROBINSON COLL, CAMBRIDGE, ENGLAND SP WHO, VACCINE HO ROBINSON COLL DE SALMONELLA; PHOP VIRULENCE REGULON; LIVE ORAL VACCINES; GENE REGULATION ID TYPHOID-FEVER; TYPHIMURIUM VIRULENCE; IMMUNOLOGIC CONTROL; ESCHERICHIA-COLI; SUICIDE VECTOR; MUTANTS; CONSTRUCTION; IMMUNOGENICITY; PATHOGENESIS; MACROPHAGE AB The PhoP virulence regulon is essential to Salmonella typhimurium mouse typhoid fever pathogenesis and survival within macrophages. This virulence regulon is composed of the PhoP (transcriptional regulator) and PhoQ (environmental sensor) proteins and the genetic loci they positively (pags for PhoP activated genes) and negatively (prgs for PhoP repressed genes) regulate. Three regulated loci pagC, pagD, and prgH, when singly mutated, affect the virulence of S. typhimurium for mice. Strains with phoP locus mutations are effective as live vaccines in mice, and strains with a constitutive regulatory mutation, a point mutation in PhoQ, can protect mice against typhoid fever when only very few organisms are administered. The addition of various PhoP regulon mutations further attenuates aroA mutants of S. typhimurium, suggesting that these mutations would be useful in further attenuating vaccine strains with metabolic pathway mutations. The phoP, phoQ, pagC, and pagD genes are highly conserved between S. typhimurium and S. typhi and may be valuable as mutations in live vaccines for human typhoid fever. A plasmid suicide vector that allows deletion of the pagC gene and stable insertion of heterologous antigen genes within the deleted pagC locus has been constructed and used successfully in S. typhimurium and S. typhi. RP MILLER, SI (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114, USA. FU NIAID NIH HHS [R01 AI30479, AI08280, K11 AI00917] NR 37 TC 45 Z9 45 U1 0 U2 2 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PY 1993 VL 11 IS 2 BP 122 EP 125 DI 10.1016/0264-410X(93)90006-J PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KH507 UT WOS:A1993KH50700006 PM 8438611 ER PT B AU CANTIELLO, HF AF CANTIELLO, HF BE Gross, P Richter, D Robertson, GL TI THE VASOPRESSIN-MEDIATED REGULATION OF RENAL SODIUM-TRANSPORT - ROLE OF THE ACTIN CYTOSKELETON IN HORMONE ACTION SO VASOPRESSIN LA English DT Proceedings Paper CT 4TH INTERNATIONAL VASOPRESSIN CONF CY MAY 23-27, 1993 CL BERLIN, GERMANY RP CANTIELLO, HF (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,RENAL UNIT,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA MONTROUGE BN 2-7420-0031-3 PY 1993 BP 357 EP 370 PG 14 WC Biochemistry & Molecular Biology; Neurosciences; Pharmacology & Pharmacy; Physiology SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Pharmacology & Pharmacy; Physiology GA BZ35P UT WOS:A1993BZ35P00030 ER PT J AU SAHLI, R FREUND, R DUBENSKY, T GARCEA, R BRONSON, R BENJAMIN, T AF SAHLI, R FREUND, R DUBENSKY, T GARCEA, R BRONSON, R BENJAMIN, T TI DEFECT IN ENTRY AND ALTERED PATHOGENICITY OF A POLYOMA-VIRUS MUTANT BLOCKED IN VP2 MYRISTYLATION SO VIROLOGY LA English DT Article ID HEPATITIS-B VIRUS; TEMPERATURE-SENSITIVE MUTANTS; CAPSID PROTEIN VP4; SIMIAN VIRUS-40; STRUCTURAL PROTEIN; TUMOR-INDUCTION; MYRISTIC ACID; VIRION PROTEIN; GENE FUNCTIONS; HOST RANGE C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. FU NCI NIH HHS [CA R35-44343, CA37667, P01-CA-50661] NR 50 TC 51 Z9 52 U1 1 U2 10 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 JAN PY 1993 VL 192 IS 1 BP 142 EP 153 DI 10.1006/viro.1993.1016 PG 12 WC Virology SC Virology GA KC982 UT WOS:A1993KC98200016 PM 8390748 ER PT J AU LONGAS, MO GARG, HG AF LONGAS, MO GARG, HG TI SULFATE COMPOSITION OF DERMATAN SULFATE FROM SCAR TISSUE SO CARBOHYDRATE RESEARCH LA English DT Note ID INFRARED-SPECTROSCOPY; HYALURONIC-ACID; HUMAN-SKIN; PROTEOGLYCANS; DERMIS; CHICK C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SHRINERS BURNS INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02114. RP LONGAS, MO (reprint author), PURDUE UNIV CALUMET,DEPT CHEM & PHYS,HAMMOND,IN 46323, USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD DEC 31 PY 1992 VL 237 BP 319 EP 324 DI 10.1016/S0008-6215(92)84255-Q PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA KH417 UT WOS:A1992KH41700028 PM 1294295 ER PT J AU CLAYTON, LK DIENER, AC LERNER, A TSE, AGD KOYASU, S REINHERZ, EL AF CLAYTON, LK DIENER, AC LERNER, A TSE, AGD KOYASU, S REINHERZ, EL TI DIFFERENTIAL REGULATION OF T-CELL RECEPTOR PROCESSING AND SURFACE EXPRESSION AFFECTED BY CD3-THETA, AN ALTERNATIVELY SPLICED PRODUCT OF THE CD3-ZETA/ETA GENE LOCUS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DISULFIDE-LINKED DIMERS; ZETA-CHAIN GENE; ANTIGEN RECEPTOR; MOLECULAR-CLONING; CD3-EPSILON SUBUNITS; GAMMA SUBUNIT; LYMPHOCYTES-T; FC-RECEPTORS; CD3 COMPLEX; ETA-CHAIN AB The T-cell receptor (TCR) is a multisubunit complex consisting of the clonotypic Tialpha and beta (or Tigamma and delta) subunits and the invariant CD3gamma, CD3delta, CD3epsilon, CD3zeta, and CD3eta subunits. Herein, we describe an additional product from the CD3zeta/eta gene locus which we have termed CD3theta. The cDNA derives from the first seven exons common to CD3zeta and CD3eta, 94 base pairs (bp) of the CD3eta-specific exon 9 and an additional exon 10 encoding the carboxyl-terminal 15 amino acids and the 3'-untranslated region. The expression of CD3theta is equivalent to that of CD3eta in tissue distribution and level of expression as judged by RNase protection analysis. Despite the identity of the amino-terminal 121 amino acids of CD3zeta, CD3eta, and CD3theta and an additional 31 amino acids shared between CD3eta and CD3theta, transfection of CD3theta into the CD3zeta-eta- T-cell hybridoma, MA5.8, failed to restore detectable surface TCR expression in contrast to transfection with CD3zeta or CD3eta. Analysis of the CD3theta protein in transfectants indicated that CD3theta is associated with the TCR intracellularly. However, unlike with CD3zeta Tialpha-beta chains remain endoglycosidase H sensitive, suggesting a role for the unique COOH-terminal segment of CD3theta in mediating TCR retention and/or degradation in a pre-Golgi compartment. C1 HARVARD UNIV,SCH MED,IMMUNOBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP CLAYTON, LK (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 55 TC 16 Z9 16 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 25 PY 1992 VL 267 IS 36 BP 26023 EP 26030 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KD073 UT WOS:A1992KD07300066 PM 1464613 ER PT J AU RUVKUN, G AF RUVKUN, G TI CELL SIGNALING - A MOLECULAR GROWTH INDUSTRY SO NATURE LA English DT Editorial Material ID HORMONE-RELEASING FACTOR; RECEPTOR; GENE; MICE C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP RUVKUN, G (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 11 TC 15 Z9 15 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 24 PY 1992 VL 360 IS 6406 BP 711 EP 712 DI 10.1038/360711a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KE472 UT WOS:A1992KE47200019 PM 1334532 ER PT J AU CAMBRIA, RP BREWSTER, DC KAUFMAN, JA SCULLY, RE KELSEY, PE AF CAMBRIA, RP BREWSTER, DC KAUFMAN, JA SCULLY, RE KELSEY, PE TI A 78-YEAR-OLD WOMAN WITH RECURRENT GASTROINTESTINAL-BLEEDING AFTER SEVERAL INTRAABDOMINAL VASCULAR OPERATIONS - EROSION OF PROSTHETIC VASCULAR GRAFT INTO DISTAL TERMINAL ILEUM SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CAMBRIA, RP (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 7 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 DEC 24 PY 1992 VL 327 IS 26 BP 1869 EP 1874 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA KD714 UT WOS:A1992KD71400008 ER PT J AU KOPANS, DB STACEYCLEAR, A AF KOPANS, DB STACEYCLEAR, A TI MAMMOGRAPHY SO LANCET LA English DT Letter ID BREAST-CANCER; MORTALITY RP KOPANS, DB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114, USA. NR 11 TC 1 Z9 1 U1 1 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD DEC 19 PY 1992 VL 340 IS 8834-5 BP 1539 EP 1540 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA KD069 UT WOS:A1992KD06900027 ER PT J AU MAESTRE, GE TATE, B MAJOCHA, RE MAROTTA, CA AF MAESTRE, GE TATE, B MAJOCHA, RE MAROTTA, CA TI CELL-SURFACE EXTENSIONS ASSOCIATED WITH OVEREXPRESSION OF ALZHEIMER-BETA/A4-AMYLOID SO BRAIN RESEARCH LA English DT Article DE AMYLOID; ALZHEIMER DISEASE; PC12; CELL MEMBRANE; BLEB; MICROVILLUS; ELECTRON MICROSCOPY; GENETIC TRANSFECTION ID PRECURSOR PROTEIN; BETA-PROTEIN; DISEASE; CORTEX; SITES AB Deposition of beta/A4 amyloid in Alzheimer disease (AD) brain parenchyma and vasculature occurs by mechanisms that are currently undefined. Similarly the potential consequences of amyloid accumulation for disrupting cellular integrity have not been addressed in detail. To investigate the possible significance of amyloid deposits for cellular viability, PC12 cells were permanently transfected with DNA coding for the beta/A4-C terminal region of the amyloid precursor protein. The DNA represented 97 amino acids of the amyloid precursor protein of which 40 amino acids were derived from the beta/A4 region. Transfected clonal cell lines and controls were examined at both the light and electron microscopic levels for morphological abnormalities. Beta/A4 amyloid accumulated in the cell membrane where the peptide was located at cellular processes resembling blebs and microvilli. These specialized structures at the cell surface were over-abundant in transfected cells that overexpressed the beta/A4 peptide but not in controls. Membranous processes may be involved in the delivery of the beta/A4 peptide to the external surface of the cell of origin and release into the extracellular space. Similar surface features of cells in the AD brain, should they occur, may indicate a role for membrane-associated processes in the pathophysiology of the disorder. C1 MASSACHUSETTS GEN HOSP,NEUROBIOL LAB,PSYCHIAT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. MCLEAN HOSP,MAILMAN RES CTR,BELMONT,MA 02178. UNIV ZULIA,FAC MED,INST INVEST BIOL,MARACAIBO,VENEZUELA. RI Maestre, Gladys/L-5092-2015 OI Maestre, Gladys/0000-0001-5690-8833 FU NIA NIH HHS [P01 AG 02126] NR 45 TC 15 Z9 16 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 DEC 18 PY 1992 VL 599 IS 1 BP 64 EP 72 DI 10.1016/0006-8993(92)90853-2 PG 9 WC Neurosciences SC Neurosciences & Neurology GA KF969 UT WOS:A1992KF96900010 PM 1493551 ER PT J AU GREEN, R SZOSTAK, JW AF GREEN, R SZOSTAK, JW TI SELECTION OF A RIBOZYME THAT FUNCTIONS AS A SUPERIOR TEMPLATE IN A SELF-COPYING REACTION SO SCIENCE LA English DT Article ID GROUP-I INTRONS; COMPLEMENTARY-STRAND RNA; DNA; TETRAHYMENA; INVITRO; BACTERIOPHAGE-T4; POLYMERASE; LIGANDS AB The sunY ribozyme is derived from a self-splicing RNA group I intron. This ribozyme was chosen as a starting point for the design of a self-replicating RNA because of its small size. As a means of facilitating the self-replication process, the size of this ribozyme was decreased by the deletion of nonconserved structural domains; however, when such deletions were made, there were severe losses of enzymatic activity. In vitro genetic selection was used to identify mutations that reactivate a virtually inactive sunY deletion mutant. A selected mutant with five substitution mutations scattered throughout the primary sequence showed greater catalytic activity than the original ribozyme under the selection conditions. The sunY ribozyme and its small selected variant can both catalyze template-directed oligonucleotide assembly. The small size and reduced secondary structure of the selected variant results in an enhancement, relative to that of the original ribozyme, of its rate of self-copying. This engineered ribozyme is able to function effectively both as a catalyst and as a template in self-copying reactions. RP GREEN, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 18 TC 102 Z9 101 U1 3 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 18 PY 1992 VL 258 IS 5090 BP 1910 EP 1915 DI 10.1126/science.1470913 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KD088 UT WOS:A1992KD08800023 PM 1470913 ER PT J AU YANG, G MASLAND, RH AF YANG, G MASLAND, RH TI DIRECT VISUALIZATION OF THE DENDRITIC AND RECEPTIVE-FIELDS OF DIRECTIONALLY SELECTIVE RETINAL GANGLION-CELLS SO SCIENCE LA English DT Article ID CHOLINERGIC AMACRINE CELLS; RABBIT RETINA; MAMMALIAN RETINA; GABA-LIKE; NEURONS; ACETYLCHOLINE; MORPHOLOGY; IMMUNOREACTIVITY; DECARBOXYLASE; RESPONSES AB Optical methods were used to locate the cell bodies of directionally selective ganglion cells in isolated rabbit retinas. These neurons detect the direction in which images move across the retinal surface and transmit that information to the brain. The receptive field of each identified cell was determined, after which the cell was injected with Lucifer yellow. An image of the receptive field border was then projected onto the fluorescent image of the dendrites, allowing precise comparison between them. The size of the receptive field matched closely the size of the dendritic arbor of that cell. This result restricts the types of convergence that can be postulated in modeling the mechanism of retinal directional selectivity. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA 02114. FU NEI NIH HHS [R37-EY01075] NR 31 TC 66 Z9 67 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 DEC 18 PY 1992 VL 258 IS 5090 BP 1949 EP 1952 DI 10.1126/science.1470920 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KD088 UT WOS:A1992KD08800036 PM 1470920 ER PT J AU BLUMENTHAL, D AF BLUMENTHAL, D TI ACADEMIC-INDUSTRY RELATIONSHIPS IN THE LIFE SCIENCES - EXTENT, CONSEQUENCES, AND MANAGEMENT SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CONFLICT-OF-INTEREST; BIOTECHNOLOGY; UNIVERSITIES AB Academic-industry relationships in the life sciences remain controversial. The available evidence suggests that such relationships have both benefits and risks for involved parties. Benefits include additional support of academic research, income for academic health centers, the potential for increased scientific and commercial productivity in both industries and universities, and enhancement of the educational experiences of students and fellows. Risks include an increase in secrecy in academic environments and damage to public support for the life science enterprise. The balance of known benefits and risks suggests that academic-industry relationships should be permitted and even selectively promoted. However, there is also a need for enhanced vigilance on the part of academic institutions and government to reduce risks posed by certain types of arrangements, especially those involving human subjects. Enhanced vigilance should include disclosure of all academic-industry relationships by life science faculty. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BLUMENTHAL, D (reprint author), MASSACHUSETTS GEN HOSP,HLTH POLICY RES & DEV UNIT,BOSTON,MA 02114, USA. NR 26 TC 43 Z9 43 U1 0 U2 6 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 DEC 16 PY 1992 VL 268 IS 23 BP 3344 EP 3349 DI 10.1001/jama.268.23.3344 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA KB732 UT WOS:A1992KB73200027 PM 1453527 ER PT J AU TAKI, J YASUDA, T FLAMM, SD HUTTER, A GOLD, HK LEINBACH, R STRAUSS, HW AF TAKI, J YASUDA, T FLAMM, SD HUTTER, A GOLD, HK LEINBACH, R STRAUSS, HW TI COMPARISON OF PAINFUL AND PAINLESS LEFT-VENTRICULAR DYSFUNCTION RECORDED DURING AMBULATORY VENTRICULAR-FUNCTION MONITORING IN ANGINA-PECTORIS SECONDARY TO CORONARY-ARTERY DISEASE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SILENT-MYOCARDIAL-ISCHEMIA; EMISSION COMPUTED-TOMOGRAPHY; STABLE ANGINA; EXERCISE; SEQUENCE; ANGIOPLASTY; INFARCTION; PERFUSION; OCCLUSION AB Left ventricular (LV) function and the electrocardiogram of 55 patients with coronary artery disease and angina were monitored for a mean of 3.2 +/- 1.9 hours with an ambulatory LV function monitor. During the monitoring interval, patients performed daily activities such as sitting, walking, climbing stairs, and eating. Sixty episodes of transient reduction in ejection fraction of >5% lasting >60 seconds were associated in 24 patients; 13 episodes were associated with typical angina, but 47 were asymptomatic. Asymptomatic episodes had a shorter duration of ventricular dysfunction (116 +/- 49 vs 189 +/- 113 seconds; p<0.05), and smaller increases in relative end-diastolic and end-systolic volumes (end-diastolic 0.9 +/- 5.4% vs 4.6 +/- 4.9% [p<0.05], and end-systolic 21 +/- 11% vs 35 +/- 20% [p<0.05]) than did symptomatic ones. When a subset of patients with both symptomatic and asymptomatic episodes were analyzed, similar results were observed: in asymptomatic episodes, duration was shorter (82 +/- 31 vs 200 +/- 110 seconds; p<0.005), ejection fraction decrease was smaller (-7.3 +/- 2.6% vs - 11.0 +/- 4.7%; p<0.05), and end-systolic volume increase was smaller (23 +/- 12% vs 37 +/- 19%; p<0.05). The data suggest that asymptomatic transient LV dysfunction is less severe and of shorter duration in patients with angina pectoris. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. NR 28 TC 5 Z9 5 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 1992 VL 70 IS 20 BP 1555 EP 1558 DI 10.1016/0002-9149(92)90456-9 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KD659 UT WOS:A1992KD65900007 PM 1466322 ER PT J AU BERSON, EL ADAMIAN, M AF BERSON, EL ADAMIAN, M TI ULTRASTRUCTURAL FINDINGS IN AN AUTOPSY EYE FROM A PATIENT WITH USHERS SYNDROME TYPE-II SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CHROMOSOME-1Q AB We studied an eye taken at autopsy from a 55-year-old woman with retinitis pigmentosa and partial deafness (Usher's syndrome type II). Two years before her death, her visual acuity was R.E.: 20/80 and L.E.: 20/50, and visual fields were constricted to a 30- to 40-degree diameter with a V4e white test light. Both rods and cones were present across the retina except for areas of the midperiphery; remaining photoreceptors had shortened or disrupted outer segments, or both, and some cones had inclusion bodies in inner segments. In the macula, most of the connecting cilia of photoreceptors appeared abnormal, with either extra microtubules or an apparent disruption of the nexin link between doublet microtubules. The pigment epithelium was abnormal across the eye, with diminished apical microvilli and basal infoldings of the plasma membrane. Possible mechanisms by which abnormal cilia could lead to photoreceptor cell death are considered. RP BERSON, EL (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY02014] NR 14 TC 23 Z9 23 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC 15 PY 1992 VL 114 IS 6 BP 748 EP 757 PG 10 WC Ophthalmology SC Ophthalmology GA KB605 UT WOS:A1992KB60500014 PM 1463045 ER PT J AU CHEN, S STROH, EM WALD, K JALKH, A AF CHEN, S STROH, EM WALD, K JALKH, A TI XANTHOMONAS-MALTOPHILIA ENDOPHTHALMITIS AFTER IMPLANTATION OF SUSTAINED-RELEASE GANCICLOVIR SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Note C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,SCHEPENS EYE RES INST,RETINA ASSOCIATES,BOSTON,MA 02114. NR 5 TC 38 Z9 38 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC 15 PY 1992 VL 114 IS 6 BP 772 EP 773 PG 2 WC Ophthalmology SC Ophthalmology GA KB605 UT WOS:A1992KB60500022 PM 1334377 ER PT J AU VONWEIZSACKER, F BLUM, HE WANDS, JR AF VONWEIZSACKER, F BLUM, HE WANDS, JR TI CLEAVAGE OF HEPATITIS-B VIRUS-RNA BY 3 RIBOZYMES TRANSCRIBED FROM A SINGLE DNA-TEMPLATE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ENZYMES C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MGH CANC CTR,MOLEC HEPATOL LAB,BOSTON,MA 02129. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-08169] NR 12 TC 63 Z9 64 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 DEC 15 PY 1992 VL 189 IS 2 BP 743 EP 748 DI 10.1016/0006-291X(92)92264-X PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KD219 UT WOS:A1992KD21900022 PM 1472046 ER PT J AU ANTIN, JH FERRARA, JLM AF ANTIN, JH FERRARA, JLM TI CYTOKINE DYSREGULATION AND ACUTE GRAFT-VERSUS-HOST DISEASE SO BLOOD LA English DT Editorial Material ID TUMOR NECROSIS FACTOR; BONE-MARROW TRANSPLANTATION; INTERLEUKIN-1 RECEPTOR ANTAGONIST; BLOOD MONONUCLEAR-CELLS; RISK-FACTORS; FACTOR-ALPHA; APLASTIC-ANEMIA; INHIBITION; ACTIVATION; TRIAL C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. RP ANTIN, JH (reprint author), BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA39542]; NIAID NIH HHS [AI30018] NR 48 TC 561 Z9 587 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1992 VL 80 IS 12 BP 2964 EP 2968 PG 5 WC Hematology SC Hematology GA KC838 UT WOS:A1992KC83800002 PM 1467511 ER PT J AU SHOWERS, MO MOREAU, JF LINNEKIN, D DRUKER, B DANDREA, AD AF SHOWERS, MO MOREAU, JF LINNEKIN, D DRUKER, B DANDREA, AD TI ACTIVATION OF THE ERYTHROPOIETIN RECEPTOR BY THE FRIEND SPLEEN FOCUS-FORMING VIRUS GP55 GLYCOPROTEIN INDUCES CONSTITUTIVE PROTEIN TYROSINE PHOSPHORYLATION SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; P70-75 BETA-SUBUNIT; INTERLEUKIN-2 RECEPTOR; IL-2 RECEPTOR; CELL-LINE; SIGNAL TRANSDUCTION; KINASE-ACTIVITY; GROWTH; FAMILY; RESPONSIVENESS C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV HEMATOL ONCOL,44 BINNEY ST,BOSTON,MA 02115. RP DANDREA, AD (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DIV HEMATOL ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [R01 DK43889-01] NR 29 TC 38 Z9 38 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 1992 VL 80 IS 12 BP 3070 EP 3078 PG 9 WC Hematology SC Hematology GA KC838 UT WOS:A1992KC83800014 PM 1467516 ER PT J AU MCDONAGH, J FOSSEL, ET KRADIN, RL DUBINETT, SM LAPOSATA, M HALLAQ, YA AF MCDONAGH, J FOSSEL, ET KRADIN, RL DUBINETT, SM LAPOSATA, M HALLAQ, YA TI EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON PEROXIDATION OF PLASMA-LIPOPROTEIN LIPIDS IN EXPERIMENTAL-ANIMALS AND PATIENTS SO BLOOD LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; LOW-DENSITY LIPOPROTEIN; MALIGNANT-TUMORS; MAXIMUM-ENTROPY; FATTY-ACIDS; CACHECTIN; CANCER; MACROPHAGES; SERUM; PRODUCTS C1 BETH ISRAEL HOSP,DEPT RADIOL,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP MCDONAGH, J (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA-43244, CA-36276]; NIDDK NIH HHS [DK-43159] NR 52 TC 28 Z9 28 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 DEC 15 PY 1992 VL 80 IS 12 BP 3217 EP 3226 PG 10 WC Hematology SC Hematology GA KC838 UT WOS:A1992KC83800031 PM 1467525 ER PT J AU PASTELLEVY, C BELL, DA ROSENBERG, AE PREFFER, F COLVIN, RB FLOTTE, TJ AF PASTELLEVY, C BELL, DA ROSENBERG, AE PREFFER, F COLVIN, RB FLOTTE, TJ TI DNA FLOW-CYTOMETRY OF EPITHELIOID SARCOMA SO CANCER LA English DT Article DE PLOIDY; SOFT TISSUE; EPITHELIOID SARCOMA; PROGNOSIS ID SOFT-TISSUE SARCOMAS; ANEUPLOIDY; DIAGNOSIS; TUMORS AB DNA ploidy of paraffin-embedded tissue from 11 patients with epithelioid sarcoma and 20 control specimens (granuloma annulare and sarcoid) was studied. DNA aneuploidy was found in 64% of the epithelioid sarcomas and in none of the control samples. Aneuploidy did not correlate with necrosis, vascular invasion, or mitotic rate. There was also no association of aneuploidy with adverse outcome. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,WELLMAN LABS,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114. NR 16 TC 14 Z9 14 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 DEC 15 PY 1992 VL 70 IS 12 BP 2823 EP 2826 DI 10.1002/1097-0142(19921215)70:12<2823::AID-CNCR2820701216>3.0.CO;2-9 PG 4 WC Oncology SC Oncology GA KB640 UT WOS:A1992KB64000013 PM 1451061 ER PT J AU AJANI, UA SEDDON, JM HSIEH, CC EGAN, KM ALBERT, DM GRAGOUDAS, ES AF AJANI, UA SEDDON, JM HSIEH, CC EGAN, KM ALBERT, DM GRAGOUDAS, ES TI OCCUPATION AND RISK OF UVEAL MELANOMA - AN EXPLORATORY-STUDY SO CANCER LA English DT Article DE OCCUPATIONAL EXPOSURES; UVEAL MELANOMA; OCULAR TUMORS; INTRAOCULAR MALIGNANT LESION; EPIDEMIOLOGY ID EXPOSURE LINKAGE SYSTEM; MALIGNANT-MELANOMA; EPIDEMIOLOGIC ASPECTS; WORKERS; CANCER; INDUSTRY; ENGLAND; WALES; EYE AB Background. Little is known about the cause of uveal melanoma, the most common primary intraocular malignant lesion in adults. This population-based case-control study evaluated occupational exposures. Methods. One hundred ninety-seven newly diagnosed cases of uveal melanoma participated. Approximately two control subjects matched for age, sex, and telephone exchange area were selected for each case by random-digit dialing. Data were collected by a structured telephone interview. Two systems of occupational coding were used: an occupation-exposure linkage system and the Bureau of Census data. Conditional logistic regression for matched studies was used to examine various occupational exposures while controlling for previously reported potential confounders and for family income. The occupation-exposure matrix was used to define clusters of cases exposed to a particular chemical group from various occupations. Results. Odds ratios were elevated for agriculture and farming work for both industry and occupation; this was consistent across both classification systems. Elevated odds ratios also were found for occupations involving machine operations, fabrication, assembling, equipment cleaning, and exposure to metal industries. Exposure to alkylating agents and phenols was associated with a lower risk compared with all other exposures. Several self-reported exposures also were studied. Exposures associated with elevated odds ratios were inks, insecticides, gases, radioactive substances, polybromated biphenyls, and chemical solvents. Conclusions. This exploratory study suggests various occupational associations for uveal melanoma and areas for future research. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RETINA SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,DAVID G COGAN OPHTHALM PATHOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP AJANI, UA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,EPIDEMIOL UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. FU NEI NIH HHS [R01 EY05076] NR 29 TC 28 Z9 29 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1992 VL 70 IS 12 BP 2891 EP 2900 DI 10.1002/1097-0142(19921215)70:12<2891::AID-CNCR2820701228>3.0.CO;2-1 PG 10 WC Oncology SC Oncology GA KB640 UT WOS:A1992KB64000025 PM 1451071 ER PT J AU LIANG, P AVERBOUKH, L KEYOMARSI, K SAGER, R PARDEE, AB AF LIANG, P AVERBOUKH, L KEYOMARSI, K SAGER, R PARDEE, AB TI DIFFERENTIAL DISPLAY AND CLONING OF MESSENGER-RNAS FROM HUMAN BREAST-CANCER VERSUS MAMMARY EPITHELIAL-CELLS SO CANCER RESEARCH LA English DT Note ID TUMOR; POLY(A); GROWTH; GENES AB Identification of the genes that are specifically expressed in tumor cells but not in normal cells (oncogenes), or vice versa (tumor suppressor genes), is important for understanding the molecular basis of cancer. The differential display technique was applied to compare mRNAs from normal and tumor-derived human mammary epithelial cells, cultured under the same conditions. Complementary DNA fragments corresponding to several apparently differentially expressed mRNAs were recovered and sequenced. They exhibit characteristics of the 3' end of eukaryotic mRNA, as predicted by the method. A complementary DNA fragment seen only in the normal cell was used as a probe to isolate its corresponding complementary DNA clone from a library. Northern analysis confirmed its differential expression. Thus, this method can be used for detecting, cloning, and sequencing of genes that are unique to a host of biological and disease processes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. RP LIANG, P (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,BOSTON,MA 02115, USA. FU NIGMS NIH HHS [GM 24571] NR 11 TC 364 Z9 391 U1 1 U2 6 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 DEC 15 PY 1992 VL 52 IS 24 BP 6966 EP 6968 PG 3 WC Oncology SC Oncology GA KB979 UT WOS:A1992KB97900039 PM 1458489 ER PT J AU FREBOURG, T BARBIER, N KASSEL, J NG, YS ROMERO, P FRIEND, SH AF FREBOURG, T BARBIER, N KASSEL, J NG, YS ROMERO, P FRIEND, SH TI A FUNCTIONAL SCREEN FOR GERM LINE P53 MUTATIONS BASED ON TRANSCRIPTIONAL ACTIVATION SO CANCER RESEARCH LA English DT Note ID FRAUMENI SYNDROME; GENE; IDENTIFICATION; PROTEIN; CANCER; EXPRESSION; FAMILY AB Germ line p53 mutations represent a genetic predisposition for cancer development. At the present time, their detection requires extensive work and their functional significance must be documented. Therefore, we have designed a simple biological assay which detects functionally significant germ line p53 mutations. This assay is based on the cloning of the patient's p53 complementary DNA into a eukaryotic expression vector followed by the cotransfection into human cells of the recombinant vector with a reporter plasmid for the transcriptional activity of p53. This assay potentially offers a powerful method to screen fibroblasts or lymphocytes from patients for germ line mutations which inactivate the p53 tumor suppressor gene. C1 MASSACHUSETTS GEN HOSP,CTR CANC,DIV MOLEC GENET,BOSTON,MA 02129. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02114. NR 26 TC 83 Z9 84 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 DEC 15 PY 1992 VL 52 IS 24 BP 6976 EP 6978 PG 3 WC Oncology SC Oncology GA KB979 UT WOS:A1992KB97900041 PM 1458490 ER PT J AU FREEMAN, GJ LOMBARD, DB GIMMI, CD BROD, SA LEE, K LANING, JC HAFLER, DA DORF, ME GRAY, GS REISER, H JUNE, CH THOMPSON, CB NADLER, LM AF FREEMAN, GJ LOMBARD, DB GIMMI, CD BROD, SA LEE, K LANING, JC HAFLER, DA DORF, ME GRAY, GS REISER, H JUNE, CH THOMPSON, CB NADLER, LM TI CTLA-4 AND CD28 MESSENGER-RNA ARE COEXPRESSED IN MOST T-CELLS AFTER ACTIVATION - EXPRESSION OF CTLA-4 AND CD28 MESSENGER-RNA DOES NOT CORRELATE WITH THE PATTERN OF LYMPHOKINE PRODUCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID I-ASSOCIATED MYELOPATHY; NEOPLASTIC-B-CELLS; COSTIMULATORY SIGNAL; LYMPHOCYTES-T; MOLECULAR-CLONING; ANTIGEN RECEPTOR; IL-2 PRODUCTION; GENE; INTERLEUKIN-2; SUPERFAMILY AB Ag-presenting cells provide at least two distinct signals for T cell activation. T cell receptor-dependent stimulation is provided by presentation of a specific peptide Ag in association with MHC molecules. In addition, APC also supply costimulatory signals required for T cell activation that are neither Ag- nor MHC restricted. One such costimulatory signal is mediated via the interaction of B7 on APC with the CD28 receptor on T cells. Recently, CTLA-4 has been shown to be a second B7 receptor on T cells. In the present report, we have examined the expression of CD28 and CTLA-4 on a panel of resting and activated normal T cell subsets and T cell clones by RNA blot analysis in an attempt to determine whether their expression defines reciprocal or overlapping subsets. CD28 was detected in resting T cells, whereas CTLA-4 was not. After stimulation with PHA and PMA for 24 h, CTLA-4 mRNA was expressed in both the CD4+ and CD8+ subsets as well as in CD28+ T cells. We examined 37 human and six murine T cell clones that had been previously characterized for their cytokine production. After activation, CTLA-4 and CD28 mRNA were coexpressed in 36 of 37 human T cell clones and all six murine T cell clones. These included T cells of CD4+8-, CD4-8+, and CD4-8- phenotypes as well as clones with Th1 and Th2 cytokine profiles. In contrast, CD28 but not CTLA-4 mRNA was detected in leukemic T cell lines and myelomas. CTLA-4 and B7 mRNA but not CD28 mRNA was detected in two long term HTLV-I-transformed T cell lines. These data demonstrate that CD28 and CTLA-4 mRNA are coexpressed in most activated T cells and T cell clones, providing evidence that they do not define reciprocal subsets. Moreover, they are consistent with the hypothesis that B7 transmits its signal through a single receptor, CD28, on resting T cells, and multiple receptors, CD28 and CTLA-4, on activated T cells. C1 HOWARD HUGHES MED INST,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CTR NEUROL DIS,BOSTON,MA 02115. UNIV MICHIGAN,DEPT MED MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. REPLIGEN CORP,CAMBRIDGE,MA 02139. USN,RES LAB,IMMUNE CELL BIOL PROGRAM,WASHINGTON,DC 20375. RP FREEMAN, GJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,MAYER 726,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-40216]; NINDS NIH HHS [R01NS24247] NR 52 TC 139 Z9 141 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1992 VL 149 IS 12 BP 3795 EP 3801 PG 7 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200004 PM 1281186 ER PT J AU GALVIN, F FREEMAN, GJ RAZIWOLF, Z HALL, W BENACERRAF, B NADLER, L REISER, H AF GALVIN, F FREEMAN, GJ RAZIWOLF, Z HALL, W BENACERRAF, B NADLER, L REISER, H TI MURINE-B7 ANTIGEN PROVIDES A SUFFICIENT COSTIMULATORY SIGNAL FOR ANTIGEN-SPECIFIC AND MHC-RESTRICTED T-CELL ACTIVATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELLS; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; EXPRESSION; INTERLEUKIN-2; RECEPTOR; PATHWAY; COMPLEX; INACTIVATION; RECOGNITION AB We have previously shown that the murine B7 (mB7) molecule, when expressed in Chinese hamster ovary cells in stable fashion, can costimulate with anti-CD3 mAb or Con A to induce T cell activation. We have now derived, by gene transfection, Chinese hamster ovary cell lines that express the I-A(d) molecule, either alone or in context with mB7. We have analyzed these transfectants for their capacity to present Ag to murine CD4+ T lymphocytes. I-A(d)/mB7-double transfectants were able to stimulate mixed lymphocyte reactions and to present peptide Ag to specific T cells. Chinese hamster ovary cells that expressed only the I-A(d) molecule were not able to stimulate T cell proliferation in these systems. Thus, the mB7 protein is a sufficient costimulatory molecule for the physiologic, Ag-dependent/MHC-restricted activation of murine CD4+ T cells. Stimulation of T cell bulk cultures resulted predominantly in the production of IL-2 and not of IL-4. The costimulatory activity of mB7 is not, however, restricted to the IL-2-secreting subset. We have identified one IL-4-secreting T cell clone, CDC35, which is responsive to mB7 triggering. Finally, we present experiments that suggest that mB7 and peptide/MHC complexes need to be expressed on the same cell for optimal induction of T cell activation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA-40216, CA-46967]; NIAID NIH HHS [AI-30169] NR 38 TC 98 Z9 98 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 DEC 15 PY 1992 VL 149 IS 12 BP 3802 EP 3808 PG 7 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200005 PM 1281187 ER PT J AU WONG, JGP KASIBHATLA, S NALEFSKI, EA RAO, A AF WONG, JGP KASIBHATLA, S NALEFSKI, EA RAO, A TI CD3- T-CELLS WITH CIS-ACTING OR TRANS-ACTING MUTATIONS AFFECTING EXPRESSION OF T-CELL RECEPTOR BETA-CHAIN MESSENGER-RNA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NUCLEAR PROTEINS INTERACT; ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; TRANSCRIPTIONAL ENHANCER; REGULATORY ELEMENTS; PROMOTER REGION; ALPHA-CHAIN; ZETA-CHAIN; GENE; COMPLEX AB Mutants of an untransformed T cell clone that no longer respond to TCR/CD3 stimulation have been derived using a selection procedure based on the loss of functional response to Ag. This functional selection gives rise to clones of several different phenotypes. We have previously described mutants with a TCR/CD3+ cell surface phenotype whose TCR are uncoupled from cellular responses. We describe six additional mutants that do not express TCR/CD3 at the cell surface. One of the CD3- clones contains a deletion in the successfully rearranged TCR-alpha gene, whereas another carries a deletion in the successfully rearranged TCR-beta gene. TCR/CD3 expression in these deletion mutants can be restored by transfection of TCR-alpha or TCR-beta DNA. Four other clones do not express TCR-beta mRNA, yet contain no obvious deletions or rearrangements in the TCR-beta genes. One of these clones does not transcribe TCR-beta chain mRNA. The mutation in this clone does not reside in the TCR-beta gene itself, but may instead reside in a trans-acting regulatory element affecting TCR-beta gene expression, because the TCR-beta mRNA- phenotype is complemented by fusion with a TCR-alpha-beta-cell line. TCR-beta chain regulatory mutants will be valuable in contributing to our understanding of how TCR expression is regulated. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,ROOM 613,MAYER BLDG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,COMM IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI22900] NR 33 TC 1 Z9 1 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 DEC 15 PY 1992 VL 149 IS 12 BP 3961 EP 3967 PG 7 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200025 PM 1334107 ER PT J AU AMBROSINO, DM BOLON, D COLLARD, H VANETTEN, R KANCHANA, MV FINBERG, RW AF AMBROSINO, DM BOLON, D COLLARD, H VANETTEN, R KANCHANA, MV FINBERG, RW TI EFFECT OF HAEMOPHILUS-INFLUENZAE POLYSACCHARIDE OUTER-MEMBRANE PROTEIN COMPLEX CONJUGATE VACCINE ON MACROPHAGES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; SEVERE COMBINED IMMUNODEFICIENCY; TUMOR NECROSIS FACTOR; NATURAL-KILLER CELLS; CAPSULAR POLYSACCHARIDE; HEMOPHILUS-INFLUENZAE; ALVEOLAR MACROPHAGES; LYMPHOCYTE-T; FACTOR-I; DISEASE AB Haemophilus influenzae type b polysaccharide-conjugate vaccines elicit protective antibody responses in young infants. One of these conjugates, polysaccharide linked to outer membrane protein complex (PRP-OMPC), is produced by linking the capsular polysaccharide to an outer membrane protein complex derived from group B Neisseria meningitidis. The outer membrane protein complex contains T cell carrier epitopes that elicit T cell-dependent antibody responses. OMPC also has been shown to increase the antibody response to other proteins administered concurrently that are not covalently linked (i.e., acts as an adjuvant). In this study PRP-OMPC immunized mice demonstrated significant increases in spleen size as well as in splenocyte number as compared to saline controls (p < 0.01, p < 0.001, respectively). No such increase was noted after immunization with another H. influenzae type b-conjugate vaccine, oligosaccharide linked to a bariant of dephtheria toxin. By analytic flow cytometry, the mice immunized with PRP-OMPC demonstrated an increase in large splenocytes expressing the Ag Mac-1 (CD11b, CR3). Furthermore, the spleens on histologic examination were characterized by an increase in the red pulp area consisting predominantly of cells of macrophage morphology. By immunohistochemical staining, the cells were identified as macrophages due to expression of Mac-1 and p150,95 (CD11C) Ag. After PRP-OMPC immunization, severe combined immunodeficient mice also demonstrated significant splenomegaly with an increase in macrophages identified by expression of Mac-1 and MHC class II Ag. Thus PRP-OMPC vaccine resulted in T cell-independent splenomegaly with an increase number of macrophages. We propose that this unique property may confer increased immunogenicity to PRP-OMPC through macrophage activation and cytokine release. Furthermore, the effect on macrophages may explain the "adjuvant" capacity of OMPC. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP AMBROSINO, DM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI29623] NR 33 TC 19 Z9 19 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 DEC 15 PY 1992 VL 149 IS 12 BP 3978 EP 3983 PG 6 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200027 PM 1460286 ER PT J AU HEAGY, W SHIPP, MA FINBERG, RW AF HEAGY, W SHIPP, MA FINBERG, RW TI OPIOID RECEPTOR AGONISTS AND CA2+ MODULATION IN HUMAN B-CELL LINES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEUTRAL ENDOPEPTIDASE 24.11; GUINEA-PIG BRAIN; T-HELPER CELLS; BETA-ENDORPHIN; LYMPHOCYTES-T; SIGNAL TRANSDUCTION; INOSITOL PHOSPHATES; OPIATE RECEPTORS; MET-ENKEPHALIN; IMMUNE-SYSTEM AB Opiates and opioid peptides have been shown to modulate lymphocyte functions; however, little attention has been given to the type of receptors or receptor signaling mechanisms that are involved. Receptor-mediated signaling via ionized free Ca2+ is an event thought to be important in the triggering of lymphocyte activities. We report use of the calcium indicator dye, indo-1, and flow cytometry to identify B lymphocyte calcium responses to physiologic concentrations of opioid peptides. The human B cell lines Nalm 6 and JY responded to the naturally occurring opioid pentapeptide methionine-enkephalin or other opiate receptor agonists with a rapid, dose-dependent rise in free cytoplasmic Ca2+. This opioid peptide effect on Ca2+ modulation was inhibited by the opiate receptor antagonist naloxone. The synthetic enkephalin analogue DAMGO with specificity for mu-type opiate receptors and the synthetic opiate receptor agonists U50,488H and U69,593 with selectivity for kappa-type sites also stimulated calcium responses when applied to the B cell lines. These studies provide evidence that human B cell lines express functional opiate receptors of the mu- and kappa-types and suggest that such receptors, coupled with Ca2+ modulation, are instrumental in the B cell response to opiates and endogenous opioid neuropeptides. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP HEAGY, W (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Finberg, Robert/E-3323-2010 FU PHS HHS [R01A129657] NR 49 TC 33 Z9 34 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 DEC 15 PY 1992 VL 149 IS 12 BP 4074 EP 4081 PG 8 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200042 PM 1334111 ER PT J AU LO, KMS VIVIER, E ROCHET, N DEHNI, G LEVINE, H HASELTINE, WA ANDERSON, P AF LO, KMS VIVIER, E ROCHET, N DEHNI, G LEVINE, H HASELTINE, WA ANDERSON, P TI INFECTION OF HUMAN NATURAL-KILLER (NK) CELLS WITH REPLICATION-DEFECTIVE HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I PROVIRUS - INCREASED PROLIFERATIVE CAPACITY AND PROLONGED SURVIVAL OF FUNCTIONALLY COMPETENT NK CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LARGE GRANULAR LYMPHOCYTES; LYMPHOMA VIRUS; PERIPHERAL-BLOOD; HTLV; TRANSFORMATION; ANTIBODIES; LINE; RETROVIRUS; RECEPTOR; FC AB Human T-cell leukemia virus type I (HTLV-I) can infect a variety of human cell types, but only T lymphocytes are efficiently immortalized after HTLV-1 infection. This study reports an attempt to infect and to immortalize NK cells with HTLV-I. Co-cultivation of freshly isolated NK cells with a HTLV-I-producing T cell line did not result in NK cell infection. However, NK cells activated with an anti-CD16 mAb and co-cultivated with a HTLV-I-producing T cell line were reproducibly infected by HTLV-I. HTLV-I infection was documented in NK cell lines and clones by the detection of defective integrated provirus by both Southern blot and polymerase chain reaction analysis. Although HTLV-I-infected NK cells produced viral proteins, they did not produce infectious viral particles. HTLV-1-infected NK cells were phenotypically indistinguishable from their uninfected counterparts (CD16+, CD2+, CD56+, CD3-). They also retained the ability to mediate both natural and antibody-dependent cell cytotoxicity. The IL-2-dependent proliferation of HTLV-I-infected NK cells was significantly greater than that of uninfected NK cells. The doubling time of this infected population was reduced from 9 days to 3 days, and the overall survival of the culture in the absence of restimulation was extended from 5 wk to 18 wk. Unlike T lymphocytes, HTLV-I-infected NK cells were not immortal, implying a fundamental difference between these two lymphocyte populations. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. FU NCI NIH HHS [R01CA53595, P30CAO6516, R01CA06516] NR 46 TC 12 Z9 12 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 DEC 15 PY 1992 VL 149 IS 12 BP 4101 EP 4108 PG 8 WC Immunology SC Immunology GA KB982 UT WOS:A1992KB98200046 PM 1460293 ER PT J AU FISHER, DE PARENT, LA SHARP, PA AF FISHER, DE PARENT, LA SHARP, PA TI MYC MAX AND OTHER HELIX LOOP HELIX LEUCINE ZIPPER PROTEINS BEND DNA TOWARD THE MINOR GROOVE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA BENDING; TRANSCRIPTION FACTORS; IMMUNOGLOBULIN ENHANCER ID LATE TRANSCRIPTION FACTOR; IMMUNOGLOBULIN ENHANCER; REGULATORY PROTEINS; BINDING; COMPLEX; DIRECTION; FAMILY; FOS; JUN AB A distinct family of DNA-binding proteins is characterized by the presence of adjacent "basic," helix-loop-helix, and leucine zipper domains. Members of this family include the Myc oncoproteins, their binding partner Max, and the mammalian transcription factors USF, TFE3, and TFEB. Consistent with their homologous domains, these proteins bind to DNA containing the same core hexanucleotide sequence CACGTG. Analysis of the conformation of DNA in protein-DNA complexes has been undertaken with a circular permutation assay. Large mobility anomalies were detected for all basic/helix-loop-helix/leucine zipper proteins tested, suggesting that each protein induced a similar degree of bending. Phasing analysis revealed that basic/helix-loop-helix/leucine zipper proteins orient the DNA bend toward the minor groove. The presence of in-phase spacing between adjacent binding sites for this family of proteins in the immunoglobulin heavy-chain enhancer suggests the possible formation of an unusual triple-bended structure and may have implications for the activities of Myc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,DEPT PEDIAT HEMATOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,DEPT ONCOL,BOSTON,MA 02115. RP FISHER, DE (reprint author), MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139, USA. NR 31 TC 70 Z9 70 U1 1 U2 3 PU NATL ACAD PRESS 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 DEC 15 PY 1992 VL 89 IS 24 BP 11779 EP 11783 DI 10.1073/pnas.89.24.11779 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400029 PM 1465398 ER PT J AU WANG, ZY GERGELY, J TAO, T AF WANG, ZY GERGELY, J TAO, T TI CHARACTERIZATION OF THE CA2+-TRIGGERED CONFORMATIONAL TRANSITION IN TROPONIN-C SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MUSCLE CONTRACTION; CALCIUM REGULATION; RESONANCE ENERGY TRANSFER ID PYRENE EXCIMER FLUORESCENCE; MUSCLE-CONTRACTION; SKELETAL-MUSCLE; ENERGY-TRANSFER; TROPOMYOSIN; RESOLUTION; PROBE AB Troponin C is the Ca2+-binding subunit of troponin in vertebrate striated muscle. Binding of Ca2+ to troponin C is thought to induce a conformational change that triggers subsequent events in the initiation of muscle contraction. A molecular modeling study has proposed that, when Ca2+ binds to the N-terminal triggering sites, helices B and C separate from the helices D and A, thereby exposing a crucial interaction site for troponin 1, the inhibitory subunit of troponin [Herzberg, O., Moult, J., and James, M. N. G. (1986) J. Biol. Chem. 261, 2638-2644]. In the present study the question of whether this separation actually occurs is addressed directly. A mutant rabbit skeletal troponin C containing a pair of cysteines at position 12 in helix A and position 49 in the polypeptide segment linking helices B and C was created by site-directed mutagenesis. Pyrene excimer fluorescence and resonance energy transfer studies on the labeled mutant troponin C reveal a Ca2+-induced increase in distance between the two cysteines. Under certain assumptions, the distance increase could be estimated from the extent of energy transfer to be almost-equal-to 13 angstrom, in good agreement with the distance increase predicted by molecular modeling. Our results provide further experimental support for the model proposed by Herzberg et al. (above). C1 BOSTON BIOMED RES INST,DEPT MUSCLE RES,20 STANIFORD ST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RP TAO, T (reprint author), BOSTON BIOMED RES INST,DEPT MUSCLE RES,20 STANIFORD ST,BOSTON,MA 02114, USA. FU NIAMS NIH HHS [AR21673] NR 16 TC 40 Z9 41 U1 1 U2 3 PU NATL ACAD PRESS 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 DEC 15 PY 1992 VL 89 IS 24 BP 11814 EP 11817 DI 10.1073/pnas.89.24.11814 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400036 PM 1465405 ER PT J AU HUANG, Q ZHOU, D CHASE, K GUSELLA, JF ARONIN, N DIFIGLIA, M AF HUANG, Q ZHOU, D CHASE, K GUSELLA, JF ARONIN, N DIFIGLIA, M TI IMMUNOHISTOCHEMICAL LOCALIZATION OF THE D1 DOPAMINE RECEPTOR IN RAT-BRAIN REVEALS ITS AXONAL-TRANSPORT, PRESYNAPTIC AND POSTSYNAPTIC LOCALIZATION, AND PREVALENCE IN THE BASAL GANGLIA, LIMBIC SYSTEM, AND THALAMIC RETICULAR NUCLEUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CORTEX; HIPPOCAMPAL FORMATION; HYPOTHALAMUS; CAUDATE PUTAMEN; SUBSTANTIA-NIGRA ID MESSENGER-RNA; MOLECULAR-CLONING; AUTORADIOGRAPHIC DISTRIBUTION; TYROSINE-HYDROXYLASE; SKF 38393; EXPRESSION; STIMULATION; STRIATUM; BINDING; NEURONS AB D1 dopamine receptor localization was examined by immunohistochemistry using a polyclonal anti-peptide antibody which (i) immunoprecipitated a protein fragment encoded by a D1 receptor cDNA and (ii) on Western blots of solubilized striatal and hippocampal membranes recognized two proteins of approximately 50 kDa and 75 kDa, corresponding to reported sizes of D1 receptor proteins. Immunoreactivity overlapped with dopamine-containing pathways, patterns of D1 receptor binding, and mRNA expression. Staining was concentrated in prefrontal, cingulate, parietal, piriform, entorhinal, and hippocampal cortical areas and subcortically in the basal ganglia, amygdala, septal area, substantia inominata, thalamus, hypothalamus, and neurohypophysis. Prominent labeling was seen in the thalamic reticular nucleus, a region known to integrate ascending basal forebrain inputs with thalamocortical and corticothalamic pathways and in fiber bundles interconnecting limbic areas. In striatal neuropil, staining appeared in spines (heads and necks), at postsynaptic sites in dendrites, and in axon terminals; in the pars reticulata of the substantia nigra, labeling was prevalent in myelinated and unmyelinated axons and dendrites. These data provide direct evidence for the regional and subcellular distribution of D1 receptor protein in the brain and for its pre- and postsynaptic localization in the basal ganglia. The prominent immunoreactivity seen in the limbic system and thalamic reticular nucleus supports an important role for this receptor subtype in mediating integrative processes involved with learning, memory, and cognition. C1 MASSACHUSETTS GEN HOSP,CELLULAR NEUROBIOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT GENET,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01655. UNIV MASSACHUSETTS,SCH MED,DEPT CELL BIOL,WORCESTER,MA 01655. RP DIFIGLIA, M (reprint author), MASSACHUSETTS GEN HOSP,CELLULAR NEUROBIOL LAB,MGH EAST,BOSTON,MA 02129, USA. FU NINDS NIH HHS [NS16367] NR 40 TC 212 Z9 212 U1 0 U2 3 PU NATL ACAD PRESS 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 DEC 15 PY 1992 VL 89 IS 24 BP 11988 EP 11992 DI 10.1073/pnas.89.24.11988 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400072 PM 1281547 ER PT J AU MOEBIUS, U CLAYTON, LK ABRAHAM, S DIENER, A YUNIS, JJ HARRISON, SC REINHERZ, EL AF MOEBIUS, U CLAYTON, LK ABRAHAM, S DIENER, A YUNIS, JJ HARRISON, SC REINHERZ, EL TI HUMAN-IMMUNODEFICIENCY-VIRUS GP120 BINDING C'C'' RIDGE OF CD4 DOMAIN-1 IS ALSO INVOLVED IN INTERACTION WITH CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HLA; AIDS; VIRUS RECEPTORS; CD4 MUTAGENESIS; T-CELL FUNCTION ID TOXIC LYMPHOCYTES-T; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODY; STRUCTURAL-ANALYSIS; FUNCTIONAL SUBSETS; CELLS RECOGNIZE; ANTIGEN; RECEPTOR; SITE; MHC AB Using site-directed mutagenesis informed by high-resolution CD4 structural data, we have investigated the role of residues of the C'C" ridge region of human CD4 on class II major histocompatibility complex (MHC) binding. This C'C" ridge is homologous to the CDR2 loop of an immunoglobulin variable domain and is known to contain the binding site for human immunodeficiency virus (HIV) coat glycoprotein gp120. Here we report that this region is also involved in interaction with class II MHC. Exposed positively charged residues Lys-35, Lys-46, and Arg-59 and the exposed hydrophobic residue Phe-43 contribute significantly to class II MHC binding. Moreover, mutations in the buried residues Trp-62 and Ser-49, which support the top and bottom of the C'C" ridge, respectively, disrupt class II MHC interaction. The HIV binding region appears to involve a restricted area of the larger class II MHC binding site on CD4. Strategies of drug design aimed at interrupting CD4-HIV interaction will need to consider the extensive overlap between class II MHC and HIV gp120 binding surfaces in this region of CD4. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV IMMUNOGENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. RP MOEBIUS, U (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI27336, AI30361] NR 47 TC 81 Z9 81 U1 0 U2 4 PU NATL ACAD PRESS 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 DEC 15 PY 1992 VL 89 IS 24 BP 12008 EP 12012 DI 10.1073/pnas.89.24.12008 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400076 PM 1465431 ER PT J AU GOLDFELD, AE FLEMINGTON, EK BOUSSIOTIS, VA THEODOS, CM TITUS, RG STROMINGER, JL SPECK, SH AF GOLDFELD, AE FLEMINGTON, EK BOUSSIOTIS, VA THEODOS, CM TITUS, RG STROMINGER, JL SPECK, SH TI TRANSCRIPTION OF THE TUMOR-NECROSIS-FACTOR-ALPHA GENE IS RAPIDLY INDUCED BY ANTIIMMUNOGLOBULIN AND BLOCKED BY CYCLOSPORINE-A AND FK506 IN HUMAN B-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE BURKITT LYMPHOMA; SPLENIC B-CELLS; IMMUNOSUPPRESSANTS; B-CELL ACTIVATION ID EPSTEIN-BARR VIRUS; LYMPHOCYTES-B; T-CELL; BINDING PROTEINS; KAPPA-B; ACTIVATION; INDUCTION; ENHANCER; FK-506; LINES AB The human tumor necrosis factor alpha (TNF-alpha) gene encodes a cytokine whose activities have been implicated in many immunopathological processes, including the activation and differentiation of lymphocytes. Originally identified as a monocyte factor, our studies and those of others have demonstrated that B and T lymphocytes produce TNF-alpha when stimulated by a variety of inducers. We report here that TNF-alpha gene transcription is rapidly and highly induced in three independently derived human Burkitt lymphoma cell lines, as well as in freshly isolated human splenic B cells, activated by antibodies to surface immunoglobulin. This burst in TNF-alpha gene transcription is associated with an induction of TNF-alpha bioactivity in the culture supernatants from stimulated splenic B cells. Moreover, induction of TNF-alpha gene transcription by anti-immunoglobulin was blocked by the immunosuppressants cyclosporin A and FK506. These studies demonstrate that TNF-alpha production is an early event in B-cell activation and they establish the efficacy of using immunosuppressants as probes in dissecting transcriptional activation pathways in human B cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,BOSTON,MA 02115. RP GOLDFELD, AE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA43143, CA47554] NR 30 TC 56 Z9 56 U1 0 U2 0 PU NATL ACAD PRESS 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 DEC 15 PY 1992 VL 89 IS 24 BP 12198 EP 12201 DI 10.1073/pnas.89.24.12198 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KC844 UT WOS:A1992KC84400115 PM 1281550 ER PT J AU RIVKEES, SA WEAVER, DR REPPERT, SM AF RIVKEES, SA WEAVER, DR REPPERT, SM TI CIRCADIAN AND DEVELOPMENTAL REGULATION OF OCT-2 GENE-EXPRESSION IN THE SUPRACHIASMATIC NUCLEI SO BRAIN RESEARCH LA English DT Note DE OCT-2 GENE EXPRESSION; SUPRACHIASMATIC NUCLEUS; CIRCADIAN RHYTHM ID FETAL BIOLOGICAL CLOCK; POU DOMAIN; MOUSE EMBRYOGENESIS; MESSENGER-RNA; PROTEINS; NEURONS; RAT; PRODUCTS; RHYTHMS; BINDING AB Oct-2 is a transcriptional activating factor that is expressed in the suprachiasmatic nuclei (SCN), the site of a biological clock. We examined in rats whether Oct-2 gene expression is regulated by the circadian pacemaker or by light using quantitative in situ hybridization. The ontogeny of Oct-2 gene expression in the SCN was also studied. Oct-2 mRNA levels remained constant throughout the circadian cycle. In contrast to c-fos mRNA levels which are acutely induced by acute light exposure at night, Oct-2 mRNA levels were not increased by light exposure at night. At gestational day 18, the first age the SCN are anatomically distinct, a prominent Oct-2 hybridization signal was present in the SCN. Our results suggest that Oct-2 is constitutively expressed in the SCN and is present from the time the SCN are discernible as discrete nuclei in fetal brain. C1 MASSACHUSETTS GEN HOSP,CHILDRENS SERV,DEV CHRONOBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [K08 HD00924, HD14227] NR 29 TC 9 Z9 9 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 DEC 11 PY 1992 VL 598 IS 1-2 BP 332 EP 336 DI 10.1016/0006-8993(92)90203-L PG 5 WC Neurosciences SC Neurosciences & Neurology GA KE924 UT WOS:A1992KE92400044 PM 1486497 ER PT J AU WORKMAN, JL KINGSTON, RE AF WORKMAN, JL KINGSTON, RE TI NUCLEOSOME CORE DISPLACEMENT INVITRO VIA A METASTABLE TRANSCRIPTION FACTOR NUCLEOSOME COMPLEX SO SCIENCE LA English DT Article ID POLYMERASE-II TRANSCRIPTION; XENOPUS-LAEVIS OOCYTES; TUMOR VIRUS PROMOTER; SACCHAROMYCES-CEREVISIAE; POSITIONED NUCLEOSOMES; HYPERSENSITIVE SITES; DNA-REPLICATION; PHO5 PROMOTER; GAL4; ACTIVATION AB In order to function, transcription factors must compete for DNA binding with structural components of chromatin, including nucleosomes. Mechanisms that could be used in this competition have been characterized with the use of the DNA binding domain of the yeast GAL4 protein. The binding of GAL4 to a nucleosome core resulted in a ternary complex containing GAL4, the core histone proteins, and DNA. This ternary complex was unstable; upon the addition of nonspecific competitor DNA, it dissociated into either the original nucleosome core particle or GAL4 bound to naked DNA. Nucleosome core destabilization by GAL4 did not require a transcriptional activation domain. These data demonstrate the displacement of nucleosome cores as a direct result of binding by a regulatory factor. Similar mechanisms might affect the establishment of factor occupancy of promoters and enhancers in vivo. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. NR 36 TC 156 Z9 157 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 11 PY 1992 VL 258 IS 5089 BP 1780 EP 1784 DI 10.1126/science.1465613 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KB964 UT WOS:A1992KB96400035 PM 1465613 ER PT J AU ROBERTS, TM AF ROBERTS, TM TI CELL BIOLOGY - A SIGNAL CHAIN OF EVENTS SO NATURE LA English DT Editorial Material ID PROTEIN-KINASE; PHOSPHORYLATION; GROWTH RP ROBERTS, TM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 18 TC 189 Z9 189 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 DEC 10 PY 1992 VL 360 IS 6404 BP 534 EP 535 DI 10.1038/360534a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KB959 UT WOS:A1992KB95900053 PM 1334231 ER PT J AU JAY, ME SILVER, MT AF JAY, ME SILVER, MT TI ACUTE BACTERIAL-ENDOCARDITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP JAY, ME (reprint author), BROCKTON W ROXBURY VET AFFAIRS MED CTR,BOSTON,MA 02132, 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 DEC 10 PY 1992 VL 327 IS 24 BP 1734 EP 1734 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA KA897 UT WOS:A1992KA89700007 PM 1435918 ER PT J AU SCHMAHMANN, JD PANDYA, DN AF SCHMAHMANN, JD PANDYA, DN TI COURSE OF THE FIBER PATHWAYS TO PONS FROM PARASENSORY ASSOCIATION AREAS IN THE RHESUS-MONKEY SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE CONNECTIONS; ASSOCIATION AREAS; CORTICOPONTINE; CEREBELLUM ID ANTERIOR CHOROIDAL ARTERY; SUPERIOR TEMPORAL SULCUS; POSTERIOR PARIETAL CORTEX; CORTICOPONTINE PROJECTION; INTRINSIC CONNECTIONS; INTERNAL CAPSULE; PYRAMIDAL TRACT; BASIS PONTIS; MACAQUE; ARCHITECTONICS AB The course of the fiber pathways to pons from parasensory association areas in the rhesus monkey was investigated by injection of tritiated amino acids and the technique of autoradiography. Results confirm the projection to pons from parasensory association areas in the temporal, parietal, and occipital lobes and extend these observations to include the posterior parahippocampal gyrus. The findings reveal that the white matter of the posterior limb of the internal capsule above the midpoint of the lateral geniculate nucleus, and at the medial aspect of the lateral geniculate nucleus, comprise common regions through which these corticopontine fibers lead to the basis pontis. The fibers demonstrate a certain degree of topographic organization in the posterior limb of the capsule above the lateral geniculate nucleus and also in the cerebral peduncle. Taken together with previous observations concerning the termination patterns of these associative corticopontine projections, it would appear that the corticopontine system consists of segregated and partially overlapping pathways. which are to some extent distinguishable anatomically at each stage of their trajectory from origin to destination. Furthermore, the existence of a common area through which all parasensory associative input to pons is transmitted suggests that a precisely located lesion in this part of the corticopontocerebellar circuit may disrupt the cerebellar access to higher order information derived from the parasensory associative regions. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BETH ISRAEL HOSP,HARVARD NEUROL UNIT,BOSTON,MA 02215. EDITH NOURSE ROGERS MEM VET ADM HOSP,BEDFORD,MA 01730. RP SCHMAHMANN, JD (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,KENNEDY 905B,14 FRUIT ST,BOSTON,MA 02114, USA. FU PHS HHS [16841] NR 68 TC 31 Z9 31 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 8 PY 1992 VL 326 IS 2 BP 159 EP 179 DI 10.1002/cne.903260202 PG 21 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA KA505 UT WOS:A1992KA50500001 PM 1479073 ER PT J AU ROTEM, A TONER, M TOMPKINS, RG YARMUSH, ML AF ROTEM, A TONER, M TOMPKINS, RG YARMUSH, ML TI OXYGEN-UPTAKE RATES IN CULTURED RAT HEPATOCYTES SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Note DE OXYGEN UPTAKE RATE; HEPATOCYTES; CELL SPREADING ID SANDWICH CONFIGURATION; TERM CULTURE; FATTY-ACIDS; STIMULATION; RESPIRATION; DEPENDENCE; MECHANISM; LIVER AB One potential treatment of acute liver failure involves the use of an extracorporeal device composed of functional hepatocytes. A major issue in the design of such a large-scale device is providing the hepatocytes with a sufficient supply of oxygen and other nutrients. In this study, we have designed and characterized a simple perfusion system and measured the oxygen uptake rate (OUR) of cultured hepatocytes using this system. The OUR of hepatocytes was determined during the first day after seeding on a single collagen gel and during the long-term stable culture after the addition of a top layer of collagen. The OUR increased to 20.7 +/- 0.57 pmol/sec/mug DNA during the first 13 hours of culture on a single collagen gel, while during the next 11 hours, the OUR declined to 10.6 +/- 1.5 pmol/sec/mug DNA. In parallel with the increase in OUR during the first 10 hours, we observed significant cell spreading, suggesting that the oxygen supply to the cells may be critical for the spreading and adaptation of the anchorage-dependent hepatocytes following isolation. Addition of a top layer of collagen to hepatocyte cultures for 24 hours of culture on a single collagen layer resulted in a stable OUR for 15 days. These results indicate that OUR of hepatocytes in culture may vary depending on the phase of culture (i.e., early vs. late) and on the extracellular environment. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. NR 26 TC 96 Z9 98 U1 1 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD DEC 5 PY 1992 VL 40 IS 10 BP 1286 EP 1291 DI 10.1002/bit.260401020 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA JX836 UT WOS:A1992JX83600019 PM 18601082 ER PT J AU KAMITANI, T MENON, AK HALLAQ, Y WARREN, CD YEH, ETH AF KAMITANI, T MENON, AK HALLAQ, Y WARREN, CD YEH, ETH TI COMPLEXITY OF ETHANOLAMINE PHOSPHATE ADDITION IN THE BIOSYNTHESIS OF GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORS IN MAMMALIAN-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VARIANT SURFACE GLYCOPROTEINS; HUMAN-ERYTHROCYTE ACETYLCHOLINESTERASE; PHOSPHATIDYLINOSITOL MEMBRANE ANCHOR; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; DECAY-ACCELERATING FACTOR; GLYCOSYL-PHOSPHATIDYLINOSITOL; STRUCTURAL CHARACTERIZATION; GLYCOLIPID PRECURSORS; RESISTANT GLYCOLIPIDS; THY-1 GLYCOPROTEIN AB Biosynthetic intermediates for the mammalian glycosylphosphatidylinositol (GPI) anchor have been described. The earliest GPI anchor precursor is N-acetylglucosaminylphosphatidylinositol, which is deacetylated to give glucosaminylphosphatidylinositol. This is followed by fatty acylation of the inositol ring, sequential addition of mannose residues donated by dolichyl mannosyl phosphate, and finally addition of ethanolamine phosphate. Here, we show that the final steps of GPI anchor biosynthesis are more complex than we have previously reported. Six distinct GPI anchor precursors were found to contain at least 1 ethanolamine phosphate residue. The headgroups of these glycolipids were purified and analyzed by a combination of Bio-Gel P4 chromatography and high resolution thin-layer chromatography. The sizes of neutral glycans were determined following HF dephosphorylation. The position of the ethanolamine phosphate residue was inferred from results of alpha-mannosidase treatment. Finally, the number of negative charges on the headgroups were determined by Mono Q chromatography. Our results show that the addition of ethanolamine phosphate is controlled by at least two different genes. Thus, the class F mutant, though unable to add ethanolamine phosphate to the third mannose residue, does incorporate ethanolamine phosphate into the first and second mannose residues. Only the wild type cells are capable of incorporating ethanolamine phosphate into the third mannose residue. Furthermore, the GPI core contains up to 3 ethanolamine phosphate residues. These results should facilitate the elucidation of the biochemical defects in paroxysmal nocturnal hemoglobinuria. C1 ROCKEFELLER UNIV,MOLEC PARASITOL LAB,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-45851]; NIAMS NIH HHS [AR-03564]; NIDDK NIH HHS [DK-40930] NR 40 TC 73 Z9 73 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 DEC 5 PY 1992 VL 267 IS 34 BP 24611 EP 24619 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA263 UT WOS:A1992KA26300070 PM 1447204 ER PT J AU TEMIZER, DH YOSHIZUMI, M PERRELLA, MA SUSANNI, EE QUERTERMOUS, T LEE, ME AF TEMIZER, DH YOSHIZUMI, M PERRELLA, MA SUSANNI, EE QUERTERMOUS, T LEE, ME TI INDUCTION OF HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH-FACTOR MESSENGER-RNA BY PHORBOL ESTER AND ANGIOTENSIN-II IN RAT AORTIC SMOOTH-MUSCLE CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; VASCULAR INJURY; GENE-EXPRESSION; MYC-GENE; ATHEROSCLEROSIS; PROLIFERATION; ATHEROGENESIS; HETEROGENEITY; TRANSCRIPTION; PATHOGENESIS AB To determine whether the gene encoding the recently identified heparin-binding epidermal growth factor-like growth factor (HB-EGF), a potent smooth muscle cell (SMC) mitogen of macrophage origin, is transcribed and regulated in vascular SMC, we isolated cDNA clones encoding rat HB-EGF from a macrophage library. Using the rat HB-EGF cDNA as a probe for RNA blot analysis, we detected low levels of HB-EGF mRNA in rat aortic SMC in culture. However, 20 nM 12-O-tetradecanoylphorbol-13-acetate (TPA) and 10(-6) M angiotensin II (AII) induced a marked increase in HB-EGF mRNA levels in rat aortic SMC (11- and 4.6-fold, respectively) that was both dose- and time-dependent. In response to TPA and AII, HB-EGF mRNA levels increased rapidly, peaked at 2 h, and returned to base line at 7 h. This effect of AII on HB-EGF induction was specific, as evidenced by the fact that it could be completely blocked by the AII antagonist saralasin. This is the first demonstration that HB-EGF is transcribed and regulated in SMC. The inducible transcription of this potent SMC mitogen gene in vascular SMC suggests that HB-EGF may have an important autocrine role in the proliferation of SMC in vascular diseases such as atherosclerosis and hypertension. C1 HARVARD UNIV,SCH PUBL HLTH,CARDIOVASC BIOL LABS,BLDG 2,665 HUNTINGTON AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,GEN MED SERV,CARDIAC UNIT,BOSTON,MA 02114. NR 36 TC 109 Z9 110 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 5 PY 1992 VL 267 IS 34 BP 24892 EP 24896 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA263 UT WOS:A1992KA26300109 PM 1447224 ER PT J AU HABER, E BODE, C MATSUEDA, GR REED, GL RUNGE, MS AF HABER, E BODE, C MATSUEDA, GR REED, GL RUNGE, MS TI ANTIBODY TARGETING AS A THROMBOLYTIC STRATEGY SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID TISSUE PLASMINOGEN-ACTIVATOR; FRAGMENT-D-DIMER; CROSS-LINKED FIBRIN; MONOCLONAL-ANTIBODY; CLOT LYSIS; ALPHA-2-PLASMIN INHIBITOR; PLATELET-AGGREGATION; HUMAN-PLASMA; UROKINASE; INVIVO C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV HEIDELBERG,W-6900 HEIDELBERG,GERMANY. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,PRINCETON,NJ 08543. PRINCETON UNIV,PRINCETON,NJ 08544. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. EMORY UNIV,ATLANTA,GA 30345. RP HABER, E (reprint author), HARVARD UNIV,SCH PUBL HLTH,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 53 TC 9 Z9 10 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD DEC 4 PY 1992 VL 667 BP 365 EP 381 DI 10.1111/j.1749-6632.1992.tb51637.x PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KJ582 UT WOS:A1992KJ58200048 PM 1309057 ER PT J AU MATSUBARA, T MOSKOWITZ, MA HUANG, ZH AF MATSUBARA, T MOSKOWITZ, MA HUANG, ZH TI UK-14,304, R(-)-ALPHA-METHYL-HISTAMINE AND SMS-201-995 BLOCK PLASMA-PROTEIN LEAKAGE WITHIN DURA-MATER BY PREJUNCTIONAL MECHANISMS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE OCTREOTIDE; SMS-201-995; SOMATOSTATIN; ALPHA-ADRENOCEPTORS; HISTAMINE H-3-RECEPTORS; MIGRAINE; NEUROGENIC INFLAMMATION; SUBSTANCE-P ID SOMATOSTATIN ANALOG; SENSORY NERVES; BLOOD-VESSELS; HEADACHE; EXTRAVASATION; STIMULATION; RAT; HISTAMINE; BRAIN; PAIN AB Intravenous administration of an alpha-adrenoceptor agonist, UK-14,304, a histamine H-3 receptor agonist, R(-)-alpha-methyl-histamine (alpha-MeHA) or SMS 201-995 (a synthetic octapeptide analogue of somatostatin), blocked plasma protein (I-125-albumin) extravasation within rat and/or guinea pig dura mater following unilateral electrical trigeminal ganglion stimulation or capsaicin administration. The extravasation caused by the administration of the neuropeptide mediator, substance P, was not inhibited by any of the three compounds. Blockade by UK-14,304 was completely antagonized by pretreatment with the highly selective alpha2-antagonist, idazoxan, as was alpha-MeHA by pretreatment with the highly selective histamine H-3 antagonist, thioperamide. Taken together, the results are consistent with blockade by prejunctional alpha2, histamine H-3 and probably somatostatin receptors which may be coupled to inhibition of neuropeptide release. Because 5-HT1-like agonists, which are useful for treating migraine and related headaches, share similar inhibitory properties in this in vivo model, the significance of prejunctional alpha2, histamine H-3 and somatostatin receptors to treatment of vascular headaches is suggested. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSURG & NEUROL SERV,BOSTON,MA 02114. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS 21558] NR 24 TC 60 Z9 64 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD DEC 2 PY 1992 VL 224 IS 2-3 BP 145 EP 150 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KB674 UT WOS:A1992KB67400006 PM 1281776 ER PT J AU MACKINNEY, AA AF MACKINNEY, AA TI DEVELOPING A CURRICULUM ON BEDSIDE DIAGNOSTIC AND THERAPEUTIC PROCEDURES SO ACADEMIC MEDICINE LA English DT Letter RP MACKINNEY, AA (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD DEC PY 1992 VL 67 IS 12 BP 840 EP 840 DI 10.1097/00001888-199212000-00008 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA KC303 UT WOS:A1992KC30300010 PM 1457018 ER PT J AU CULLEN, DJ MACAULAY, A AF CULLEN, DJ MACAULAY, A TI CONSISTENCY BETWEEN PEER REVIEWERS FOR A CLINICAL SPECIALTY JOURNAL SO ACADEMIC MEDICINE LA English DT Article ID REJECTION RATES; AGREEMENT; CONSENSUS AB To analyze the consistency between independent peer reviewers in evaluating and ranking unsolicited articles, the authors used paired reviews of 422 unsolicited submissions to the Journal of Clinical Anesthesia from the end of 1988 through 1991. (The editors of this journal base their publication decisions, to a substantial degree, on congruence of their reviewers' recommendations). The reviewers were chosen for their interest in reviewing and areas of expertise. Their recommendations were ranged along a continuum of four categories: (1) accept outright, (2) accept with revision, (3) reject in present form (article could be revised and submitted again as a new submission), and (4) reject outright. The pairs of peer reviewers were consonant for 169 papers (40%), differed by one category for 168 papers (40%), differed by two categories for 73 papers (17%), and differed by three categories for 12 papers (3%). Thus, most articles' reviews were in consonance or close to it; articles reviewed by two members of the editorial board, however, were significantly less likely to be consonant (32%) than were those reviewed by two nonmembers (44%, chi-square, p = .027). C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 11 TC 14 Z9 14 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD DEC PY 1992 VL 67 IS 12 BP 856 EP 859 DI 10.1097/00001888-199212000-00013 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA KC303 UT WOS:A1992KC30300015 PM 1457023 ER PT J AU DORIA, A WARRAM, JH KROLEWSKI, AS AF DORIA, A WARRAM, JH KROLEWSKI, AS TI MOLECULAR METHODS FOR THE STUDY OF THE GENETIC-DETERMINANTS OF NEPHROPATHY IN TYPE-1 (INSULIN-DEPENDENT) DIABETES SO ACTA DIABETOLOGICA LA English DT Article; Proceedings Paper CT INTERNATIONAL MEETING ON THE STATE-OF-THE-ART AND NEW PERSPECTIVES IN DIABETIC NEPHROPATHY CY MAR 06-07, 1992 CL UNIV PADUA, PADUA, ITALY HO UNIV PADUA DE ANGIOTENSINOGEN GENE; INSULIN RECEPTOR GENE; METHODS OF MOLECULAR GENETICS; NEPHROPATHY IN TYPE-1 (INSULIN-DEPENDENT) DIABETES ID FRAGMENT-LENGTH-POLYMORPHISMS; CONVERTING ENZYME GENE; PROTEIN KINASE-C; RENIN GENE; ESSENTIAL-HYPERTENSION; ANGIOTENSINOGEN GENE; BLOOD-PRESSURE; SUSCEPTIBILITY; DNA; COUNTERTRANSPORT AB Recently, evidence has accumulated that genetic factors may contribute to the development of diabetic nephropathy in patients with type 1 (insulin-dependent) diabetes mellitus. To identify variation at a gene locus, newly developed methods are introduced which employ denaturing gradient gel electrophoresis (DGGE) to study sequence differences in polymerase chain reaction (PCR)-amplified DNA fragments as well as in genomic DNA. These techniques are illustrated with studies of the angiotensinogen gene and the insulin receptor gene. In preliminary data from a comparison between individuals with and without diabetic nephropathy, we found no DNA sequence difference in the part of the angiotensinogen gene coding for angiotensin I. We did find, however, different distributions of a DNA polymorphism detected with the probe corresponding to exons 7 and 8 of the insulin receptor gene in RsaI DGGE blots in a comparison of patients with slow and fast progressing nephropathy. The interpretation of this finding and the need for further studies are discussed. In conclusion, the advent of methods of molecular genetics makes possible studies on genetic determinants of diabetic nephropathy. However, more clinical and epidemiological data are needed to find out how many genes are involved and how they interact with exposure to diabetes. Foremost, DNA from families with two or more siblings with diabetic nephropathy must be collected so that genetic studies will be possible. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,EPIDEMIOL & GENET SECT,1 JOSLIN PL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. NR 53 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD DEC PY 1992 VL 29 IS 3-4 BP 136 EP 141 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LK103 UT WOS:A1992LK10300006 ER PT J AU GRAHAM, DY GO, MF EVANS, DJ AF GRAHAM, DY GO, MF EVANS, DJ TI UREASE, GASTRIC AMMONIUM AMMONIA, AND HELICOBACTER-PYLORI - THE PAST, THE PRESENT, AND RECOMMENDATIONS FOR FUTURE-RESEARCH SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review AB The presence of ammonium in gastric contents was described in 1852; urease activity in the stomach was identified 70 years later. The discovery of gastric urease resulted in intense research activity to discover its origin, function, and relation to the gastric levels of ammonium and urea. Interest in urease waned in the 1960s as most pertinent questions appeared to have been addressed and there was strong evidence that gastric urease was not a property of the stomach but was of microbial origin. Identification of Helicobacter pylori as the source of urease in the stomach in the last decade has resulted in a rebirth of interest in gastric urease and its products.1-15 There is little actual evidence to support a role for toxicity of ammonia in relation to H. pylori and the bulk of the evidence suggests that the products of urease activity are not toxic and may even be beneficial. The purpose of this review is to examine the older literature and to examine new findings in the perspective of what is already known and to suggest areas remaining to be examined. We ask, 'What is old, what is new, and what needs to be done?' C1 BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,DIV MOLEC VIROL,HOUSTON,TX 77030. RP GRAHAM, DY (reprint author), VET AFFAIRS MED CTR 111D,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. FU NIDDK NIH HHS [DK 39919] NR 0 TC 44 Z9 45 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD DEC PY 1992 VL 6 IS 6 BP 659 EP 669 PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA KD504 UT WOS:A1992KD50400001 PM 1486153 ER PT J AU SINGER, DE HUGHES, RA GRESS, DR SHEEHAN, MA OERTEL, LB MARAVENTANO, SW BLEWETT, DR ROSNER, B KISTLER, JP AF SINGER, DE HUGHES, RA GRESS, DR SHEEHAN, MA OERTEL, LB MARAVENTANO, SW BLEWETT, DR ROSNER, B KISTLER, JP TI THE EFFECT OF ASPIRIN ON THE RISK OF STROKE IN PATIENTS WITH NONRHEUMATIC ATRIAL-FIBRILLATION - THE BAATAF STUDY SO AMERICAN HEART JOURNAL LA English DT Article ID THROMBOEMBOLIC COMPLICATIONS; RANDOMIZED TRIAL; PREVENTION; FRAMINGHAM; WARFARIN; THERAPY AB Recent randomized trials have consistently demonstrated the marked efficacy of warfarin in reducing the risk of stroke caused by nonrheumatic atrial fibrillation. These trials have provided conflicting evidence on the effect of aspirin. We report the aspirin analysis from the BAATAF study, a trial in which control patients could choose to take aspirin. There were two strokes in 446 person-years with warfarin (annual rate of 0.45%); eight strokes in 206 person-years with aspirin, most at 325 mg per day (annual rate of 3.9%); and five strokes in 271 person-years among patients taking neither aspirin nor warfarin (annual rate of 1.8%). Simultaneously controlling for the other significant determinants of stroke in the BAATAF study (age, mitral annular calcification, and clinical heart disease), the relative rates (95% confidence interval) of stroke were: (1) warfarin/aspirin = 0.135 (0.029 to 0.64); (2) aspirin/(no aspirin and no warfarin) = 1.95 (0.64 to 5.97); and (3) warfarin/(no aspirin and no warfarin) 0.263 (0.051 to 1.36). Our "treatment received" analysis argues that warfarin is strikingly more effective than aspirin in preventing stroke in nonrheumatic atrial fibrillation. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,STROKE SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SINGER, DE (reprint author), MASSACHUSETTS GEN HOSP,MED SERV,GEN INTERNAL MED UNIT,BULFINCH 1,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL 33233-05] NR 24 TC 57 Z9 58 U1 0 U2 2 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 DEC PY 1992 VL 124 IS 6 BP 1567 EP 1573 DI 10.1016/0002-8703(92)90074-6 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KB242 UT WOS:A1992KB24200024 PM 1462916 ER PT J AU FAVA, M LITTMAN, A LAMONFAVA, S MILANI, R SHERA, D MACLAUGHLIN, R CASSEM, E LEAF, A MARCHIO, B BOLOGNESI, E GUARALDI, GP AF FAVA, M LITTMAN, A LAMONFAVA, S MILANI, R SHERA, D MACLAUGHLIN, R CASSEM, E LEAF, A MARCHIO, B BOLOGNESI, E GUARALDI, GP TI PSYCHOLOGICAL, BEHAVIORAL AND BIOCHEMICAL RISK-FACTORS FOR CORONARY-ARTERY DISEASE AMONG AMERICAN AND ITALIAN MALE CORPORATE MANAGERS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PLASMA APOLIPOPROTEIN-B; HEART-DISEASE; CARDIOVASCULAR-DISEASE; STRESS; MORTALITY; CHOLESTEROL; POPULATION; HOSTILITY; PROGRAM; PATTERN AB Differences in psychological, behavioral and biochemical risk factors for coronary artery disease (CAD) among male corporate managers of 2 countries (United States and Italy), with very different age-specific rates of mortality for CAD were evaluated. In all, 129 American (mean age 43 +/- 7 years) and 80 Italian (mean age 45 +/- 7 years) managers volunteered to participate in this study. Each subject was administered several questionnaires assessing various psychological and behavioral risk factors for CAD, and all 129 Americans and SS of 80 Italians had their blood drawn between 8:00 and 9:30 Am after overnight fasting for the measurement of plasma levels of dehydroepiandrosterone-sulfate (DHEA-S), total cholesterol, triglycerides, and apolipoproteins A-I and B. Italian managers reported significantly more cynicism and hostility, and less enjoyment in leisure activities than did American ones. Furthermore, 40 Italian (51%) and only 18 American (14%) managers were smokers (this difference being statistically significant). Although no significant differences were found in factors positively related with CAD (cholesterol, triglycerides and apolipoprotein B), there were clear differences in parameters inversely correlated with the incidence of CAD. Italian managers had significantly lower levels of plasma DHEA-S and apolipoprotein A-I than did American ones. In conclusion, this study found that Italian managers had a significantly more unhealthy psychological and behavioral profile than did American ones, and had lower levels of those biochemical parameters (apolipoprotein A-I and DHEA-S) thought to have a protective role against development of CAD. C1 MASSACHUSETTS GEN HOSP,DEPT PREVENT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. TUFTS UNIV,USDA,HUMAN NUTR RES CTR,LIPID METAB LAB,BOSTON,MA 02111. UNIV MODENA,SCH MED,DEPT PSYCHIAT,I-41100 MODENA,ITALY. RP FAVA, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CLIN PSYCHOPHARMACOL UNIT,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. RI Milani, Richard/A-6045-2011 NR 30 TC 13 Z9 13 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 1992 VL 70 IS 18 BP 1412 EP 1416 DI 10.1016/0002-9149(92)90291-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KA272 UT WOS:A1992KA27200008 PM 1442610 ER PT J AU EICHHORN, JH BELL, DA YOUNG, RH SWYMER, CM FLOTTE, TJ PREFFER, FI SCULLY, RE AF EICHHORN, JH BELL, DA YOUNG, RH SWYMER, CM FLOTTE, TJ PREFFER, FI SCULLY, RE TI DNA CONTENT AND PROLIFERATIVE ACTIVITY IN OVARIAN SMALL-CELL CARCINOMAS OF THE HYPERCALCEMIC TYPE - IMPLICATIONS FOR DIAGNOSIS, PROGNOSIS, AND HISTOGENESIS SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE OVARY; SMALL CELL CARCINOMA; FLOW CYTOMETRY; PLOIDY; S PHASE; HISTOGENESIS; PROGNOSIS ID FLOW CYTOMETRIC ANALYSIS; GRANULOSA TUMORS; PLOIDY; CANCER; LUNG AB Ovarian small cell carcinoma of the hypercalcemic type is a rare cancer of young women of unclear histogenesis. Although usually lethal, a subset of patients with stage I tumors have survived. Twenty-five cases of small cell carcinoma (17 stage I, 1 stage II, and 7 stage III) were evaluated by flow cytometric analysis performed on paraffin-embedded tissue. Forty classifiable histograms from 23 cases were DNA diploid; histograms from two cases could not be interpreted. The mean S-phase fraction was 10.5% (4.7% to 18.4%), and the mean G2/M fraction was 5% (1.5% to 19.5%) in 22 cases. Mean values of mitotic rate, S-phase fraction, G2/M fraction, and proliferation index (%S + %G2/M) were not associated with stage or outcome, nor did any proliferation variable correlate with interval to death. A comparative review of flow cytometric findings in other types of ovarian cancer that may be confused with small cell carcinoma indicates that flow cytometry is an objective diagnostic aid to distinguish small cell carcinoma of the hypercalcemic type from other forms of small cell carcinoma, malignant germ cell tumors, and sex-cord tumors, and that small cell carcinoma probably does not belong in either the surface epithelial or germ cell categories of ovarian cancer. Finally, the flow cytometric findings in this report exemplify the rare phenomenon of a diploid DNA content in a very lethal tumor and indicate that an accurate diagnosis of tumor type is essential before a prognosis on the basis of flow cytometric data can be made. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT LABS,BOSTON,MA 02114. NR 33 TC 33 Z9 34 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 1992 VL 98 IS 6 BP 579 EP 586 PG 8 WC Pathology SC Pathology GA KB877 UT WOS:A1992KB87700008 PM 1334364 ER PT J AU TRUHAN, AP TUNNESSEN, WW AF TRUHAN, AP TUNNESSEN, WW TI PICTURE OF THE MONTH - MASTOCYTOSIS SO AMERICAN JOURNAL OF DISEASES OF CHILDREN LA English DT Note C1 MASSACHUSETTS GEN HOSP,PEDIAT DERMATOL SERV,BOSTON,MA 02114. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0002-922X J9 AM J DIS CHILD JI Am. J. Dis. Child. PD DEC PY 1992 VL 146 IS 12 BP 1473 EP 1474 PG 2 WC Pediatrics SC Pediatrics GA KC118 UT WOS:A1992KC11800024 PM 1456262 ER PT J AU BRANDT, B GREGER, V YANDELL, D PASSARGE, E HORSTHEMKE, B AF BRANDT, B GREGER, V YANDELL, D PASSARGE, E HORSTHEMKE, B TI A SIMPLE AND NONRADIOACTIVE METHOD FOR DETECTING THE RB1.20 DNA POLYMORPHISM IN THE RETINOBLASTOMA GENE SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. RP BRANDT, B (reprint author), UNIV ESSEN GESAMTHSCH KLINIKUM,INST HUMAN GENET,W-4300 ESSEN 1,GERMANY. NR 2 TC 24 Z9 25 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1992 VL 51 IS 6 BP 1450 EP 1451 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA KC995 UT WOS:A1992KC99500030 PM 1463022 ER PT J AU CANEZ, MS SAMUELS, MH LUTHER, MF KING, TS SCHENKEN, RS AF CANEZ, MS SAMUELS, MH LUTHER, MF KING, TS SCHENKEN, RS TI COCAINE IMPAIRS GONADOTROPIN-SECRETION IN OOPHORECTOMIZED MONKEYS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE COCAINE; REPRODUCTIVE DYSFUNCTION; PRIMATES ID FEMALE RHESUS-MONKEY; PROGESTERONE; DISPOSITION; PREGNANCY; ESTROGEN; HUMANS AB OBJECTIVE: Our objective was to determine whether cocaine alters gonadotropin secretion in oophorectomized monkeys. STUDY DESIGN: Oophorectomized monkeys with elevated gonadotropin levels were chronically cannulated to allow blood sampling every 15 minutes. Monkeys received either saline solution or 2 or 4 mg/kg cocaine hydrochloride as an intravenous bolus. Other oophorectomized monkeys were pretreated with either saline solution or 4 mg/kg cocaine 2 hours before bolus gonadotropin-releasing hormone administration, and plasma luteinizing hormone and follicle-stimulating hormone levels were measured every 15 minutes for 3 hours. Monkeys were also given either saline solution or 4 mg/kg of cocaine with gonadotropin-releasing hormone simultaneously, and plasma gonadotropin levels were measured every 15 minutes for 3 hours. Serum luteinizing hormone and follicle-stimulating hormone levels were measured by radioimmunoassay. RESULTS: Both doses of cocaine resulted in a significant decrease in luteinizing hormone levels compared with controls. Follicle-stimulating hormone levels were significantly decreased only with the 4 mg/kg dose of cocaine. There was no difference in luteinizing hormone and follicle-stimulating hormone responses to gonadotropin-releasing hormone in the cocaine-treated monkeys compared with saline solution-treated monkeys by using repeated-measures analysis of variance. CONCLUSION: These findings demonstrate that acute cocaine administration to oophorectomized primates inhibits basal luteinizing hormone-follicle-stimulating hormone secretion but not gonadotropin-releasing hormone-stimulated luteinizing hormone and follicle-stimulating hormone release. In the absence of an effect on gonadotropin-releasing hormone-stimulated gonadotropin release, we conclude that the impaired luteinizing hormone-follicle-stimulating hormone secretion after cocaine administration is due in part to a direct effect of cocaine on gonadotropin-releasing hormone neurons or on hypothalamic neurotransmitter modulation of gonadotropin-releasing hormone release. C1 UNIV TEXAS,HLTH SCI CTR,DEPT OBSTET & GYNECOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY VET HOSP,DEPT RES & DEV,SAN ANTONIO,TX. NR 26 TC 12 Z9 12 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 1992 VL 167 IS 6 BP 1785 EP 1793 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA KD429 UT WOS:A1992KD42900050 PM 1471699 ER PT J AU BHATTA, N ANDERSON, RR FLOTTE, T SCHIFF, I HASAN, T NISHIOKA, NS AF BHATTA, N ANDERSON, RR FLOTTE, T SCHIFF, I HASAN, T NISHIOKA, NS TI ENDOMETRIAL ABLATION BY MEANS OF PHOTODYNAMIC THERAPY WITH PHOTOFRIN-II SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE PHOTODYNAMIC THERAPY; ENDOMETRIAL ABLATION; PHOTOFRIN ID ND-YAG LASER; PHOTORADIATION THERAPY; HYSTERECTOMY; MENORRHAGIA; IMPLANTS; TUMORS AB OBJECTIVE: Photodynamic therapy is a technique in which tissue is irradiated with light after the use of a photosensitizing drug that produces singlet oxygen, which has a cytotoxic effect. The feasibility of using photodynamic therapy with photofrin II for endometrial ablation was studied. STUDY DESIGN: Fifty-eight rabbits were studied. Preferential uptake of photofrin II by endometrial tissue, compared with the myometrium, was established by drug extraction and fluorescence microscopy after administration of photofrin II intravenously. Dosimetry for endometrial ablation was established by administering photofrin II in 1, 2, 5, and 10 mg/kg doses and laser light (630 nm) at radiant exposures of 100 and 200 J/cm2. Histologic examination was performed at 24 hours, 5 days, and 10 days after treatment. There were two control groups. One group received laser light but no photofrin II, and the other received photofrin II without laser light. RESULTS: The concentration of photofrin II was three times higher in the endometrium than in the myometrium at doses of 1 and 2 mg/kg. Fluorescence microscopy of frozen sections of endometrium and myometrium showed a predominantly perivascular fluorescence from photofrin II. A dose of 1 and 2 mg/kg and a flow of 100 J/cm2 was adequate for endometrial ablation in rabbits. At 24 hours after treatment there was extensive hemorrhage and evidence of cell death in the entire endometrium and mild hemorrhage in 10% to 50% of the inner circular layer of the myometrium. At 5 days after treatment necrosis of the entire endometrium and the inner half of the myometrium was seen, but the outer half of the myometrium and the serosa were normal. There were no Gases of uterine perforation. Similar results were seen at 10 days after treatment, except for the additional presence of inflammatory cells. Neither control group (drug without light, light without drug) showed any injury to the endometrium at 24 hours. CONCLUSION: We conclude that endometrial ablation can be effectively achieved in rabbits by means of photodynamic therapy with photofrin II without significant complications. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BHATTA, N (reprint author), MASSACHUSETTS GEN HOSP,VINCENT GYNECOL SERV,WELLMAN LABS PHOTOMED,WELLMAN 2,BOSTON,MA 02114, USA. NR 31 TC 38 Z9 38 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 1992 VL 167 IS 6 BP 1856 EP 1863 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA KD429 UT WOS:A1992KD42900061 PM 1471710 ER PT J AU SCHOFIELD, DE FLETCHER, JA AF SCHOFIELD, DE FLETCHER, JA TI TRISOMY 12 IN PEDIATRIC GRANULOSA-STROMAL CELL TUMORS - DEMONSTRATION BY A MODIFIED METHOD OF FLUORESCENCE INSITU HYBRIDIZATION ON PARAFFIN-EMBEDDED MATERIAL SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID OVARY AB The use of fluorescence in situ hybridization (FISH) to detect chromosomal abnormalities bas many applications. Use of FISH on archival, paraffin-embedded material bas been limited to microscopic sections. We have carried out FISH on preparations of disaggregated nuclei obtained from paraffin-embedded tissue to evaluate chromosome 12 copy number in granulosa-stromal cell neoplasms occurring in infants, children, and adolescents. Trisomy 12 was detected in the majority of cells from three of four juvenile granulosa cell tumors (three ovarian and one testicular) and one malignant granulosa cell tumor Tetrasomy 12 was observed in a case of ovarian thecoma. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. RP SCHOFIELD, DE (reprint author), CHILDRENS HOSP MED CTR,DEPT PATHOL,300 LONG WOOD AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [1K11CA01498-02] NR 14 TC 68 Z9 68 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 DEC PY 1992 VL 141 IS 6 BP 1265 EP 1269 PG 5 WC Pathology SC Pathology GA KC122 UT WOS:A1992KC12200002 PM 1466394 ER PT J AU MUNRO, JM LO, SK CORLESS, C ROBERTSON, MJ LEE, NC BARNHILL, RL WEINBERG, DS BEVILACQUA, MP AF MUNRO, JM LO, SK CORLESS, C ROBERTSON, MJ LEE, NC BARNHILL, RL WEINBERG, DS BEVILACQUA, MP TI EXPRESSION OF SIALYL-LEWIS X, AN E-SELECTIN LIGAND, IN INFLAMMATION, IMMUNE PROCESSES, AND LYMPHOID-TISSUES SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; GRANULE MEMBRANE-PROTEIN; HUMAN-ENDOTHELIAL-CELLS; WEIBEL-PALADE BODIES; NODE HOMING RECEPTOR; POST-MORTEM TISSUES; T-CELLS; VASCULAR ENDOTHELIUM; CARBOHYDRATE LIGAND; SIALOSYLATED LEWIS AB The carbohydrate structure sialyl-Lewis X (SLe(x)) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLe(x) by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLe(x). Cell surface SLe(x) was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN both within vessels and extravasated, expressed SLe(x). A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLe(x). These observations are consistent with the concept that SLe(x) on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLe(x) positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix Whether the SLe(x) antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP BEVILACQUA, MP (reprint author), UNIV CALIF SAN DIEGO,HOWARD HUGHES MED INST,LA JOLLA,CA 92093, USA. FU NHLBI NIH HHS [P01-HL 36028] NR 64 TC 105 Z9 108 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 DEC PY 1992 VL 141 IS 6 BP 1397 EP 1408 PG 12 WC Pathology SC Pathology GA KC122 UT WOS:A1992KC12200016 PM 1281620 ER PT J AU DELAMONTE, SM SPRATT, RA CHONG, J GHANBARI, HA WANDS, JR AF DELAMONTE, SM SPRATT, RA CHONG, J GHANBARI, HA WANDS, JR TI IMMUNOHISTOCHEMICAL AND HISTOPATHOLOGIC CORRELATES OF ALZHEIMERS DISEASE-ASSOCIATED ALZ-50 IMMUNOREACTIVITY QUANTIFIED IN HOMOGENATES OF CEREBRAL TISSUE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PAIRED HELICAL FILAMENTS; PROGRESSIVE SUPRANUCLEAR PALSY; HIPPOCAMPAL COMPLEX SUBFIELDS; MONOCLONAL-ANTIBODY ALZ-50; HUMAN BRAIN-TISSUE; TAU-PROTEINS; LEWY BODIES; NEUROFIBRILLARY TANGLES; PICK BODIES; DEMENTIA AB Alz-50 is a monoclonal antibody that immunoreacts with neurofibrillary tangles and neurites in brains with Alzheimer's disease (AD). In addition, the levels of Alz-50 immunoreactivity in brain, measured by either enzyme-linked immunosorbent assay or ALZ-enzyme-linked immunosorbent assay (EIA), are increased in AD relative to age-matched controls. The current study compares the distribution and extent of Alz-50 immunostaining with quantified levels of Alz-50 immunoreactivity measured in adjacent frozen blocks of tissue by ALZ-EIA The brain tissue studied was obtained from individuals with AD, AD + Down's syndrome (AD + DN), Parkinson's disease with dementia (PD), or AD + PD, and from nondemented aged controls. In AD, AD + DN and AD + PD, there were significantly higher densities of Alz-50-immunoreactive (AFI) neurons, more abundant diffuse AFI neurites, and higher ALZ-EIA values than in aged controls. In PD, the overall mean density of AFI neurons was significantly lower than in AD and AD + DN, but AFI neurites were as abundant as they were in brains with an AD diagnosis. However, PD was readily distinguished from AD and AD + DN by significantly lower mean ALZ-HA values, and significantly lower densities of neurofilament-immuno-reactive AD lesions. Multiple-regression analysis demonstrated significant correlations between ALZ-EIA levels and the severity of AD lesions, and the density of AFI neurites, but not with the density of AFI neurons. Therefore, ALZ-EIA levels may represent only a portion of the Alz-50 immunoreactivity detectable by immunohistochemical staining. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ALZHEIMERS DIS RES CTR,DIV NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DIV MED SERV,BOSTON,MA 02114. ABBOTT LABS,DIV RES & DEV,ABBOTT PK,IL. RP DELAMONTE, SM (reprint author), MGH,CTR CANC,MGH E,149 13TH ST,BOSTON,MA 02129, USA. FU NIA NIH HHS [K11-AG00425]; NIAAA NIH HHS [R01-AA-02666]; NINDS NIH HHS [R01 NS29793] NR 49 TC 3 Z9 3 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 DEC PY 1992 VL 141 IS 6 BP 1459 EP 1469 PG 11 WC Pathology SC Pathology GA KC122 UT WOS:A1992KC12200022 PM 1466403 ER PT J AU JONES, R AF JONES, R TI ULTRASTRUCTURAL ANALYSIS OF CONTRACTILE CELL-DEVELOPMENT IN LUNG MICROVESSELS IN HYPEROXIC PULMONARY-HYPERTENSION - FIBROBLASTS AND INTERMEDIATE CELLS SELECTIVELY REORGANIZE NONMUSCULAR SEGMENTS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GRANULATION-TISSUE; RAT; OXYGEN; ARTERIES; MYOFIBROBLAST; EXPOSURE; RETURN; AIR AB The current study traces the development of contractile cells in the nonmuscular segments of rat lung microvessels in hyperoxic pulmonary hypertension. New intimal cells first develop into a well-defined layer beneath the endothelium and internal to an elastic lamina Ultrastructurally, these cells are found to be 1) fibroblasts recruited to the vessel wall from the interstitium and 2) intermediate cells, a population of preexisting vascular cells (structurally between a smooth muscle cell and a pericyte). Early in hyperoxia (days 3 through 7), interstitial fibroblasts migrate and align around the smallest vessels in which an elastic lamina is either absent or fragmentary. These cells then are incorporated into the vessel wall by tropoelastin secretion and the formation of an elastic lamina along their abluminal margin. After day 7, the new mural fibroblasts acquire the features of contractile cells, namely a basal lamina, extensive microfilaments, and dense bodies. In other vessels, as early as days of hyperoxia, intermediate cells within the vessel intima begin to acquire the additional filaments and dense bodies of contractile cells. As hyperoxia continues, each cell pathway gives rise to vessels with distinct intimal or medial layers of contractile cells. In this way, thick-walled 'newly muscularized' vessel segments form adjacent to the capillary bed. C1 CHILDRENS HOSP MED CTR,DEPT PATHOL,BOSTON,MA 02115. RP JONES, R (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,MOLEC & CELL BIOL LAB,E 149 13TH ST,BOSTON,MA 02129, USA. FU NHLBI NIH HHS [R01 HL34552] NR 28 TC 38 Z9 40 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 DEC PY 1992 VL 141 IS 6 BP 1491 EP 1505 PG 15 WC Pathology SC Pathology GA KC122 UT WOS:A1992KC12200025 PM 1466406 ER PT J AU ROSOWSKY, A AF ROSOWSKY, A TI DEVELOPMENT OF NEW ANTIFOLATE ANALOGS AS ANTICANCER AGENTS SO AMERICAN JOURNAL OF PHARMACEUTICAL EDUCATION LA English DT Article; Proceedings Paper CT 93RD ANNUAL MEETING OF THE AMERICAN ASSOC OF COLLEGES OF PHARMACY CY JUL 12-15, 1992 CL WASHINGTON, DC SP AMER ASSOC COLL PHARM ID THYMIDYLATE SYNTHASE INHIBITORS; 5,10-DIDEAZA-5,6,7,8-TETRAHYDROFOLIC ACID DDATHF; GLYCINAMIDE RIBONUCLEOTIDE FORMYLTRANSFERASE; FOLYLPOLYGLUTAMATE SYNTHETASE-ACTIVITY; BENZOYL RING MODIFICATIONS; DENOVO PURINE SYNTHESIS; MURINE TUMOR-MODELS; 5,10-DIDEAZATETRAHYDROFOLIC ACID; DIHYDROFOLATE-REDUCTASE; ANTITUMOR-ACTIVITY C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP ROSOWSKY, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 109 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC COLL PHARMACY PI ALEXANDRIA PA 1426 PRINCE STREET, ALEXANDRIA, VA 22314-2815 SN 0002-9459 J9 AM J PHARM EDUC JI Am. J. Pharm. Educ. PD WIN PY 1992 VL 56 IS 4 BP 453 EP 463 PG 11 WC Education, Scientific Disciplines; Pharmacology & Pharmacy SC Education & Educational Research; Pharmacology & Pharmacy GA KF916 UT WOS:A1992KF91600027 ER PT J AU SABOLIC, I VALENTI, G VERBAVATZ, JM VANHOEK, AN VERKMAN, AS AUSIELLO, DA BROWN, D AF SABOLIC, I VALENTI, G VERBAVATZ, JM VANHOEK, AN VERKMAN, AS AUSIELLO, DA BROWN, D TI LOCALIZATION OF THE CHIP28 WATER CHANNEL IN RAT-KIDNEY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE IMMUNOFLUORESCENCE; IMMUNOGOLD ELECTRON MICROSCOPY; PROXIMAL TUBULE; THIN LIMB OF HENLE; MEMBRANE PERMEABILITY; INTEGRAL MEMBRANE PROTEIN ID INTEGRAL MEMBRANE-PROTEIN; ANTIDIURETIC-HORMONE; PROXIMAL TUBULE; BRUSH-BORDER; COATED PITS; BAND-3; MICROSCOPY; VESICLES; CORTEX AB CHIP28 is an integral membrane protein that has been identified as the erythrocyte water channel and that is also expressed in the kidney. Antibodies against erythrocyte CHIP28 were used to localize this protein along the rat urinary tubule. By Western blotting, CHIP28 was detected in kidney plasma membrane and endosome fractions. With the use of immunocytochemistry, CHIP28 was located in brush-border and basolateral plasma membranes of the proximal tubule. The initial S1 segment was weakly stained, but the S2 and S3 segments were heavily labeled. Subapical vesicles were also positive. Apical and basolateral membranes of the long thin descending limb were strongly labeled, but ascending thin and thick limbs of Henle and distal convoluted tubules were negative. Some vasa recta profiles in the medulla were positive. CHIP28 is, therefore, present in membranes with a high constitutive water permeability, where it probably acts as a transmembrane water-conducting channel. Finally, a weak staining of apical and basolateral membranes of cortical collecting duct principal cells was detectable, suggesting a potential relationship of CHIP28 to the vasopressin-sensitive water channel. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. FU NIDDK NIH HHS [DK-38452] NR 33 TC 247 Z9 247 U1 0 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 DEC PY 1992 VL 263 IS 6 BP C1225 EP C1233 PN 1 PG 9 WC Physiology SC Physiology GA KF375 UT WOS:A1992KF37500012 PM 1282299 ER PT J AU ZEIDLER, A EDWARDS, P GOLDMAN, J KORT, S MEEHAN, WP LEVIN, SR AF ZEIDLER, A EDWARDS, P GOLDMAN, J KORT, S MEEHAN, WP LEVIN, SR TI HYPERGLYCEMIC ATHYMIC NUDE-MICE - FACTORS AFFECTING INVITRO INSULIN-SECRETION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PANCREAS; PERFUSION; GLUCOSE; SOMATOSTATIN; NON-INSULIN-DEPENDENT DIABETES-MELLITUS ID DIABETES-MELLITUS; MOUSE AB The strain of athymic nude male mice (ANM) developed at the University of Southern California (USC) exhibits spontaneous hyperglycemia and relative hypoinsulinemia in vivo. To investigate factors that influence insulin secretion in this animal model of non-insulin-dependent diabetes mellitus, we utilized the isolated perfused mouse pancreas of the ANM-USC and control BALB/c mice. We compared in vitro glucose-induced insulin secretion in ANM-USC and control mice, inhibition of secretion by somatostatin, and variability of insulin secretion over the two-year period it took to complete these experiments. Glucose-induced insulin secretion from the isolated pancreas was biphasic in both ANM-USC and controls. Insulin secretion was quantitatively equal to or greater than control mice, depending on the phase-of secretion analyzed and the source of the control mice. In contrast to pancreases of control mice, insulin secretion from ANM-USC pancreases was relatively resistant to inhibition of insulin secretion by somatostatin. Variability in insulin secretion over the two years in which these experiments were performed was greater from pancreases of control than that observed from pancreases of the ANM-USC. The hyperglycemic ANM-USC mouse does not demonstrate diminished insulin secretion in vitro yet is relatively hypoinsulinemic in vivo. Thus circulating factors other than somatostatin might contribute to the insulinopenic stage in this animal model. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,DIABET RES LAB,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA 90024. UNIV MICHIGAN,HENRY FORD HOSP,DETROIT,MI 48202. RP ZEIDLER, A (reprint author), UNIV SO CALIF,LOS ANGELES CTY MED CTR,SCH MED,1200 N STATE ST,RM 8250,LOS ANGELES,CA 90033, USA. NR 15 TC 1 Z9 1 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 DEC PY 1992 VL 263 IS 6 BP E1131 EP E1133 PN 1 PG 3 WC Physiology SC Physiology GA KF375 UT WOS:A1992KF37500041 ER PT J AU WEAVER, DR REPPERT, SM AF WEAVER, DR REPPERT, SM TI ADENOSINE RECEPTOR GENE-EXPRESSION IN RAT-KIDNEY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PURINERGIC RECEPTORS; TUBULOGLOMERULAR FEEDBACK; JUXTAGLOMERULAR APPARATUS; COLLECTING DUCT ID RENIN SECRETION; A1; BRAIN; VISUALIZATION; CLONING; TISSUES AB Adenosine is an important modulator of renal function. Adenosine produced and released within the kidney is thought to participate in the metabolic regulation of glomerular filtration (tubuloglomerular feedback), as well as in regulating renal excretory function and renin secretion. The recent cloning of cDNAs encoding the A1 and A2a adenosine receptors from rat brain allows direct examination of potential sites of adenosine action within the rat kidney. Northern blot analysis of rat kidney poly(A)+ RNA revealed that A1 adenosine receptor mRNA was more abundant in kidney than the A2a adenosine receptor transcript. In situ hybridization With S-35-labeled cRNA probes was used to localize A1 and A2a adenosine receptor mRNAs within the kidney. A1 adenosine receptor mRNA was most abundant in the collecting ducts of the papilla and inner medulla. Collecting ducts in the outermost portion of the inner stripe of the outer medulla and cells of the juxtaglomerular apparatus also expressed A1 adenosine receptor mRNA. A2a adenosine receptor mRNA was localized to the renal papilla. The distribution of A1 and A2a adenosine receptor mRNAs within the rat kidney supports previously postulated roles for adenosine in the regulation of renal hemodynamics, excretory function, and renin secretion. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02114. RP WEAVER, DR (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS SERV,DEV CHRONOBIOL LAB,JACKSON 1226,BOSTON,MA 02114, USA. FU NIDDK NIH HHS [DK-42125] NR 20 TC 90 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 DEC PY 1992 VL 263 IS 6 BP F991 EP F995 PN 2 PG 5 WC Physiology SC Physiology GA KF377 UT WOS:A1992KF37700079 PM 1481890 ER PT J AU COURSIN, DB CIHLA, HP OBERLEY, TD OBERLEY, LW AF COURSIN, DB CIHLA, HP OBERLEY, TD OBERLEY, LW TI IMMUNOLOCALIZATION OF ANTIOXIDANT ENZYMES AND ISOZYMES OF GLUTATHIONE-S-TRANSFERASE IN NORMAL RAT LUNG SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SUPEROXIDE DISMUTASE; CATALASE; GLUTATHIONE PEROXIDASE; IMMUNOGOLD; IMMUNOHISTOCHEMISTRY ID SUPEROXIDE-DISMUTASE ACTIVITY; LOWER RESPIRATORY-TRACT; SYRIAN-HAMSTER TISSUES; OXYGEN-TOXICITY; IMMUNOHISTOCHEMICAL LOCALIZATION; KIDNEY DEVELOPMENT; II CELLS; METABOLISM; HYPEROXIA; CATALASE AB Polyclonal antisera to manganese and copper-zinc superoxide dismutases, catalase, glutathione peroxidase (GPx), and isozymes of glutathione S-transferase (liver and placental isolates, GST-L and GST-P, respectively) were used to localize these enzymes in normal rat lung by immunostaining. Light-microscopic results, using an immunoperoxidase technique, were expanded on by electron-microscopic immunogold localization. The findings were consistent with previous biochemical work. However, both GPx and GST-P were predominantly localized to extracellular connective tissue of the lung. These findings demonstrate the basal antioxidant enzyme phenotypes for parenchymal lung tissue at light- and electron-microscopic levels. Significant components of enzymatic defense to oxidant stress are heterogeneously distributed throughout rat lung tissue including both epithelial cell surfaces and the extracellular matrix. C1 UNIV WISCONSIN,SCH MED,DEPT ANESTHESIOL,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,DEPT INTERNAL MED,MADISON,WI 53705. UNIV WISCONSIN,SCH MED,DEPT PATHOL,MADISON,WI 53705. WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL SERV,MADISON,WI 53705. UNIV IOWA,COLL MED,RADIAT RES LAB,IOWA CITY,IA 52242. FU NCI NIH HHS [CA-41267] NR 42 TC 47 Z9 47 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 DEC PY 1992 VL 263 IS 6 BP L679 EP L691 PN 1 PG 13 WC Physiology SC Physiology GA KF375 UT WOS:A1992KF37500076 PM 1282303 ER PT J AU LI, ZY DANIEL, EE LANE, CG ARNAOUT, MA OBYRNE, PM AF LI, ZY DANIEL, EE LANE, CG ARNAOUT, MA OBYRNE, PM TI EFFECT OF AN ANTI-MO1 MAB ON OZONE-INDUCED AIRWAY INFLAMMATION AND AIRWAY HYPERRESPONSIVENESS IN DOGS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; EXPOSURE; THROMBOXANE; ADHESION; RESPONSIVENESS; INHALATION; MONOCYTES; HISTAMINE; INJURY; LUNG AB Ozone inhalation causes neutrophil migration into the airway and airway hyperresponsiveness in dogs. The leukocyte adhesion molecule Mo1 (CD11b/CD18) is a heterodimeric glycoprotein the expression of which is necessary for neutrophil adhesion to endothelium. To evaluate the contribution of Mo1 to ozone-induced neutrophil influx and airway hyperresponsiveness, six dogs were treated intravenously with an Anti-Mo1 monoclonal antibody (3.75 mg/kg in normal saline) that binds to both human and canine Mo1, or the diluent alone, 1.5 h before inhaling ozone (3 ppm for 30 min), or dry air. Airway responses to doubling doses of inhaled acetylcholine (ACh) were measured before and after inhalation of ozone. Neutrophil influx was assessed by bronchoalveolar lavage (BAL) performed after the second ACh inhalation. Treatment with anti-Mo1 prevented the ozone-induced influx of neutrophils into BAL. After diluent and inhaled dry air, the neutrophil count in BAL was 1.49 +/- 1.26 (SE) X 10(4) (5.0% of total cells). After diluent and inhaled ozone, the neutrophil count increased to 7.27 +/- 3.22 (SE) X 10(4) (22.6% of total cells)(P < 0.05). After anti-Mo1 and inhaled ozone, the neutrophil count was 1.48 +/-0.62 (SE) X 10(4) (8.5% of total cells). Treatment with anti-Mo1 also significantly reduced the number of eosinophils in BAL after ozone. Ozone-induced ACh airway hyperresponsiveness was not prevented by treatment with anti-Mo1. These results indicate that expression of Mo1 is necessary for ozone-induced neutrophil migration into the airway lumen. C1 MCMASTER UNIV,DEPT MED,DIV PHYSIOL & PHARMACOL,DEPT BIOMED SCI,ASTHMA RES GRP,HAMILTON L8N 3Z5,ONTARIO,CANADA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,RENAL UNIT,BOSTON,MA 02114. NR 27 TC 29 Z9 29 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD DEC PY 1992 VL 263 IS 6 BP L723 EP L726 PN 1 PG 4 WC Physiology SC Physiology GA KF375 UT WOS:A1992KF37500080 PM 1476207 ER PT J AU CHEW, FS LEV, MH AF CHEW, FS LEV, MH TI POLYETHYLENE OSTEOLYSIS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PROSTHESES C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP CHEW, FS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 5 TC 7 Z9 7 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 DEC PY 1992 VL 159 IS 6 BP 1254 EP 1254 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JZ240 UT WOS:A1992JZ24000023 PM 1442395 ER PT J AU SCHNITT, SJ CONNOLLY, JL TAVASSOLI, FA FECHNER, RE KEMPSON, RL GELMAN, R PAGE, DL AF SCHNITT, SJ CONNOLLY, JL TAVASSOLI, FA FECHNER, RE KEMPSON, RL GELMAN, R PAGE, DL TI INTEROBSERVER REPRODUCIBILITY IN THE DIAGNOSIS OF DUCTAL PROLIFERATIVE BREAST-LESIONS USING STANDARDIZED CRITERIA SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE BREAST DISEASE; HYPERPLASIA; ATYPICAL HYPERPLASIA; CARCINOMA INSITU; INTEROBSERVER REPRODUCIBILITY ID TERM FOLLOW-UP; CANCER; DISEASE; RISK; WOMEN AB Although the categorization of proliferative breast lesions provides valuable information regarding subsequent risk of breast cancer, the ability of pathologists to classify such lesions in a reproducible fashion has not been adequately evaluated. To assess further interobserver reproducibility in the categorization of proliferative breast lesions, six pathologists each reviewed 24 proliferative ductal lesions and classified them as either usual hyperplasia (H), atypical hyperplasia (AH), or carcinoma in situ (CIS). Before evaluation of the study slides, all the participants were instructed to use the diagnostic criteria of Page and co-workers and were provided with both a written summary of these criteria and a set of teaching slides with representative examples of each type of lesion. Complete agreement among all six pathologists was seen in 14 cases (58%); five or more agreed in 17 cases (71%); and four or more arrived at the same diagnosis in 22 cases (92%). No pathologist consistently rendered more "benign" or "malignant" diagnoses than any other. After assigning numerical values for each diagnostic category (H = 1, AH = 2, CIS = 3), the scores for the group of 24 cases did not differ significantly by pathologist (p = 0.68; average score range, 1.7-2.0). Our results indicate that with the use of standardized criteria, interobserver concordance in the diagnosis of proliferative ductal breast lesions can be obtained in the majority of cases. C1 UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA 22903. ARMED FORCES INST PATHOL,DEPT GYNECOL & BREAST PATHOL,WASHINGTON,DC 20306. VANDERBILT UNIV,MED CTR,DEPT PATHOL,NASHVILLE,TN 37240. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. STANFORD UNIV,MED CTR,DEPT PATHOL,STANFORD,CA 94305. RP SCHNITT, SJ (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 16 TC 295 Z9 309 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 1992 VL 16 IS 12 BP 1133 EP 1143 DI 10.1097/00000478-199212000-00001 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA KC319 UT WOS:A1992KC31900001 PM 1463092 ER PT J AU ZITNIK, RJ COOPER, JAD RANKIN, JA SUSSMAN, J AF ZITNIK, RJ COOPER, JAD RANKIN, JA SUSSMAN, J TI EFFECTS OF INVITRO AMIODARONE EXPOSURE ON ALVEOLAR MACROPHAGE INFLAMMATORY MEDIATOR PRODUCTION SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE ALVEOLAR MACROPHAGE; AMIODARONE; FIBRONECTIN; LEUKOTRIENES; SUPEROXIDE ID LIGAND RECEPTOR DYNAMICS; PULMONARY TOXICITY; SIGNAL AMPLIFICATION; GROWTH-FACTOR; NEUTROPHIL; FIBRONECTIN; FIBROBLASTS; MECHANISMS; LUNG AB Administration of amiodarone, although often lifesaving, is associated with pulmonary side effects. Patients with amiodarone pulmonary toxicity can present with either a chronic disorder that suggests pulmonary fibrosis or a more acute process. Mechanisms of acute pulmonary injury resulting from amiodarone are unclear. Previous studies have demonstrated that the drug is preferentially concentrated in alveolar macrophages. In the present study, the authors examined whether in vitro exposure to amiodarone resulted in alteration of rat alveolar macrophage superoxide, leukotriene B4, or fibronectin release. In addition, the authors assessed whether macrophages were ultrastructurally altered by in vitro amiodarone exposure. Twenty four hour exposure to therapeutic tissue concentrations of amiodarone resulted in enhancement of phorbol myristate acetate-stimulated macrophage superoxide release. In addition, 48 hours exposure to amiodarone caused a dose-dependent inhibition of spontaneous fibronectin release by macrophages. Macrophages exposed to 48 hours of 10 mug/ml amiodarone were ultrastructurally abnormal, containing lamellar inclusions and demonstrating a large degree of vacuolization. The authors concluded that alveolar macrophages are very sensitive to therapeutic tissue concentrations of amiodarone. Alteration of macrophage mediator release by amiodarone may be one mechanism for lung damage induced by the drug. C1 UNIV ALABAMA,DIV PULM & CRIT CARE MED,PULM SECT,UNIV STN,BIRMINGHAM,AL 35294. BIRMINGHAM VAMC,PULM SECT,BIRMINGHAM,AL. YALE UNIV,SCH MED,DEPT PATHOL,PULM SECT,NEW HAVEN,CT 06510. NR 23 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 1992 VL 304 IS 6 BP 352 EP 356 DI 10.1097/00000441-199212000-00004 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA KB474 UT WOS:A1992KB47400004 PM 1333729 ER PT J AU GEE, JE MILLER, DM AF GEE, JE MILLER, DM TI STRUCTURE AND APPLICATIONS OF INTERMOLECULAR DNA TRIPLEXES SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Review DE CHEMICAL PROBING; CHEMOTHERAPY; DNA BINDING DRUGS; INTERMOLECULAR DNA TRIPLEX ID SITE-SPECIFIC CLEAVAGE; HELIX-FORMING OLIGONUCLEOTIDES; SEQUENCE-SPECIFIC RECOGNITION; DUPLEX DNA; MAJOR GROOVE; ALPHA-OLIGODEOXYNUCLEOTIDES; INTERCALATING AGENTS; TARGETED CLEAVAGE; NUCLEIC-ACIDS; NEUTRAL PH AB Current DNA binding drugs are not sequence specific. Triplex-forming oligonucleotides will bind targeted duplex DNA sites in a sequence-specific manner. A new class of DNA binding molecules based on triple-helical DNA formation promises a sequence-specific method of targeting discrete regions of DNA. DNA modifying molecules linked to third strands have been shown to modify only regions of DNA to which they were targeted. Current research will increase the understanding of triplex DNA structure and will lead to improved DNA binding drugs. C1 UNIV ALABAMA,DEPT INTERNAL MED,520 WTI,BHFB 288,UAB STN,BIRMINGHAM,AL 35294. BIRMINGHAM VA MED CTR,BIRMINGHAM,AL. UNIV ALABAMA,DEPT BIOCHEM,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR COMPREHENS CANC,BIRMINGHAM,AL 35294. FU NCI NIH HHS [CA 42664, CA 42337] NR 74 TC 20 Z9 20 U1 3 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD DEC PY 1992 VL 304 IS 6 BP 366 EP 372 DI 10.1097/00000441-199212000-00008 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KB474 UT WOS:A1992KB47400008 PM 1456276 ER PT J AU MATTIA, AR AF MATTIA, AR TI PERIANAL MASS AND RECURRENT CELLULITIS DUE TO ENTEROBIUS-VERMICULARIS SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID VAGINAL PARASITOSIS; GRANULOMA; PINWORM; PERITONEUM AB A unique case of enterobiasis presenting as recurrent cellulitis and a perianal mass in a six-year-old girl is reported. Complicated perianal lesions due to Enterobius are unusual. Only 10 previous cases are known, with unclear pathogenesis in most of them, although mucosal breaches and perianal crypt or gland entry have been postulated. The association of the mass in this case with a deep crypt, and the histopathologic finding of squamous epithelium focally surrounding the granulomatous reaction to the Enterobius eggs suggest that the worm entered the perianal tissues via a crypt. Local secondary bacterial infection can cause significant morbidity. Surgical excision of such granulomatous mass lesions is necessary in symptomatic or complicated cases. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP MATTIA, AR (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,WARREN 2,BOSTON,MA 02114, USA. NR 26 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 1992 VL 47 IS 6 BP 811 EP 815 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA KF920 UT WOS:A1992KF92000013 PM 1471739 ER PT J AU GOUDSOUZIAN, NG DENMAN, W ANAES, FC CLEVELAND, R SHORTEN, G AF GOUDSOUZIAN, NG DENMAN, W ANAES, FC CLEVELAND, R SHORTEN, G TI RADIOLOGIC LOCALIZATION OF THE LARYNGEAL MASK AIRWAY IN CHILDREN SO ANESTHESIOLOGY LA English DT Article DE ANESTHESIA, PEDIATRIC; EQUIPMENT, LARYNGEAL MASK; RADIOLOGIC DIAGNOSTIC PROCEDURES, COMPUTED TOMOGRAPHY, MAGNETIC RESONANCE IMAGING; RADIOLOGIC LOCALIZATION, LARYNGEAL MASK ID INSERTION AB In the absence of data on the anatomic localization of the cuff of the laryngeal mask airway (LMA) in children, radiologic images were obtained from 50 infants and children (aged 1 month to 15 yr) undergoing diagnostic radiologic procedures during halothane and N2O:O2 anesthesia. In 46 patients, the cuff of the LMA was in the pharynx and covered the laryngeal opening. The upper (proximal) section was adjacent to the base of the tongue at the level of C1 or C2 vertebrae pushing the tongue forward and its lower (distal) end was in the inferior recesses of the hypopharynx at the levels of C4 to T1 vertebrae. The cuff of LMA at this position between the base of the tongue above the epiglottis and below the laryngeal opening, covered the laryngeal aperture, forming a low pressure seal at the entrance of the larynx. In 37 of these 46 patients, a posterior deflection of the epiglottis was noted (<45-degrees), and in only 9, the epiglottis was in the anatomic position. In four patients, the cuff of the LMA was located in the oropharynx. No correlation was found between the size of the LMA and the position of the epiglottis with respect to end-tidal CO2, respiratory rate, or the leak pressures. The size of the LMA, its anatomic location, and the position of the epiglottis had no significant effect on the respiratory parameters of spontaneously breathing children. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. RP GOUDSOUZIAN, NG (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 11 TC 76 Z9 76 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD DEC PY 1992 VL 77 IS 6 BP 1085 EP 1089 DI 10.1097/00000542-199212000-00007 PG 5 WC Anesthesiology SC Anesthesiology GA KC865 UT WOS:A1992KC86500007 PM 1466460 ER PT J AU DELAMONTE, SM VOLICER, L HAUSER, SL WANDS, JR AF DELAMONTE, SM VOLICER, L HAUSER, SL WANDS, JR TI INCREASED LEVELS OF NEURONAL THREAD PROTEIN IN CEREBROSPINAL-FLUID OF PATIENTS WITH ALZHEIMERS-DISEASE SO ANNALS OF NEUROLOGY LA English DT Article ID NEUROFIBRILLARY TANGLES; SECRETORY PROTEIN; SENILE DEMENTIA; TAU TAU; DIAGNOSIS; BRAIN; ALPHA-1-ANTICHYMOTRYPSIN; NEUROFILAMENT AB Neuronal thread protein is a recently characterized, approximately 20-kd protein that accumulates in brains with Alzheimer's disease (AD) lesions. This study examined whether concentrations of neuronal thread protein (NTP) were also increased in the cerebrospinal fluid (CSF) of individuals with probable (clinically diagnosed) and definite (histopathologically proved) AD. Using a highly sensitive three-site monoclonal antibody-based immunoradiometric assay, we measured NTP concentrations in CSF from 84 patients with probable AD and mild dementia (duration, 4.05 +/- 0.36 years), 45 with Parkinson's disease and minimal or no dementia (duration, 4.73 +/- 0.78 years), 73 with multiple sclerosis, and 73 nondemented control subjects. NTP concentrations were also measured in postmortem ventricular fluid and temporal lobe neocortex extracts from 31 subjects with histopathologically proved AD and 14 age-matched control subjects. The mean concentration of NTP in the CSF was higher in AD (4.15 +/- 0.25 ng/ml; 95% confidence interval [CI] limits, 3.65-4.65) than in Parkinson's disease (1.96 +/- 0.16 ng/ml; 95% CI, 1.65-2.27), multiple sclerosis (1.6 +/- 0.14 ng/ml; 95% CI limits, 1.33-1.88), or control subjects (1.27 +/- 0.06 ng/ml; 95% CI limits, 1.15-1.40) (p < 0.001). In addition, 70% of the patients with probable AD had concentrations of NTP in CSF that were higher than 2.5 ng/ml (> upper 99% CI limit in the control group), compared with 23% of Parkinson's disease patients, 11% of multiple sclerosis patients, and 4% of control subjects. The mean concentrations of NTP in the ventricular fluid and brain tissue from individuals with documented AD and end-stage dementia were threefold higher than the levels detected in the CSF from the remaining patients with probable AD and mild dementia. Moreover, of 9 patients with AD, postmortem brain and CSF manifested 5- to 50-fold higher levels of NTP compared with the CSF samples obtained an average of 6 years earlier. These findings demonstrate that NTP levels are elevated in the CSF of individuals with AD and that NTP levels in the CSF increase strikingly with progression of dementia and neuronal degeneration. C1 BOSTON UNIV,SCH MED,BEDFORD VET ADM HOSP,CTR GERIATR RES EDUC CLIN,BOSTON,MA 02118. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. RI Hauser, Stephen/J-2978-2016 FU NIA NIH HHS [P50 AG05134]; NIAAA NIH HHS [R01-AA02666]; NINDS NIH HHS [R01-NS29793] NR 27 TC 46 Z9 46 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1992 VL 32 IS 6 BP 733 EP 742 DI 10.1002/ana.410320606 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA KC150 UT WOS:A1992KC15000004 PM 1471863 ER PT J AU HYMAN, BT MARZLOFF, K WENNIGER, JJ DAWSON, TM BREDT, DS SNYDER, SH AF HYMAN, BT MARZLOFF, K WENNIGER, JJ DAWSON, TM BREDT, DS SNYDER, SH TI RELATIVE SPARING OF NITRIC-OXIDE SYNTHASE CONTAINING NEURONS IN THE HIPPOCAMPAL-FORMATION IN ALZHEIMERS-DISEASE SO ANNALS OF NEUROLOGY LA English DT Note ID LONG-TERM POTENTIATION; SOMATOSTATIN-NEUROPEPTIDE-Y; NADPH-DIAPHORASE; EXCITOTOXIN LESIONS; MESSENGER; GLUTAMATE AB Nitric oxide (NO) is an endogenous neuromodulator that may mediate neurotoxic effects of glutamate. NO- synthesizing neurons are, however, resistant to NO- and glutamate-induced neurotoxicity. We now show that NO synthase neurons are selectively spared in patients with Alzheimer's disease, even in a severely affected region of the brain such as the hippocampal formation. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. JOHNS HOPKINS UNIV,DEPT NEUROSCI,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT NEUROL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT PHARMACOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT MOLEC SCI,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,DEPT PSYCHIAT,BALTIMORE,MD 21218. RP HYMAN, BT (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,32 FRUIT ST,BOSTON,MA 02114, USA. FU NIA NIH HHS [AG08487]; NIDA NIH HHS [DA-00266]; NIMH NIH HHS [MH-18501] NR 26 TC 156 Z9 161 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 1992 VL 32 IS 6 BP 818 EP 820 DI 10.1002/ana.410320618 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA KC150 UT WOS:A1992KC15000016 PM 1281971 ER PT J AU GLICK, JH GELBER, RD GOLDHIRSCH, A SENN, HJ AF GLICK, JH GELBER, RD GOLDHIRSCH, A SENN, HJ TI ADJUVANT THERAPY OF PRIMARY BREAST-CANCER - 4TH INTERNATIONAL-CONFERENCE ON ADJUVANT THERAPY OF PRIMARY BREAST-CANCER ST-GALLEN, SWITZERLAND SO ANNALS OF ONCOLOGY LA English DT Editorial Material C1 OSPED CIVICO LUGAND,LUGANO,ITALY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. KANTONSSPITAL,CTR ONCOL,CH-9006 ST GALLEN,SWITZERLAND. RP GLICK, JH (reprint author), UNIV PENN,CTR CANC,6 PENN TOWER,3400 SPRUCE ST,PHILADELPHIA,PA 19104, USA. NR 24 TC 21 Z9 21 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD DEC PY 1992 VL 3 IS 10 BP 801 EP 807 PG 7 WC Oncology SC Oncology GA KB206 UT WOS:A1992KB20600009 PM 1286043 ER PT J AU NADOL, JB XU, WZ AF NADOL, JB XU, WZ TI DIAMETER OF THE COCHLEAR NERVE IN DEAF HUMANS - IMPLICATIONS FOR COCHLEAR IMPLANTATION SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE COCHLEAR IMPLANT; COCHLEAR NERVE ID SENSORINEURAL HEARING-LOSS; SPIRAL GANGLION-CELLS; HUMAN AUDITORY-NERVE; RETROGRADE DEGENERATION; STIMULATION; PREDICTORS; SURVIVAL AB Although the parameters that are most important for postoperative speech perception in cochlear implantation have not been identified, it is assumed that the numbers of remaining cochlear neurons and spiral ganglion cells in the implanted deaf ears are critical. In this study, we evaluated the correlation of the maximum diameter of the cochlear and vestibular nerve trunks with the number of spiral ganglion cells in horizontal sections of the temporal bone of 42 patients who were profoundly deaf during life, and in 5 patients with normal hearing. The maximum diameters of the cochlear, vestibular, and eighth cranial nerves were significantly smaller in the deaf population as compared to normal-hearing controls. In addition, the counts of the remaining spiral ganglion cells were significantly correlated with the maximum diameter of the cochlear (p = .0006), vestibular (p = .001), and eighth cranial nerves (p = .0003). The regression equation estimated that 25% of the variance of the spiral ganglion cell count was predicted by the maximum diameter of the eighth nerve. Although the results of this study suggest that preoperative radiographic imaging of the diameter of the eighth nerve may be helpful in predicting the residual spiral ganglion cell count, the wide variability of diameters of the eighth nerve in hearing and deaf subjects militates against this theoretic usefulness. 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 [P01 DC00361] NR 33 TC 39 Z9 41 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD DEC PY 1992 VL 101 IS 12 BP 988 EP 993 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA KB899 UT WOS:A1992KB89900005 PM 1463299 ER PT J AU LAURENCIN, CT HORAN, RF SENATUS, PB WHEELER, CB LIPSON, SJ AF LAURENCIN, CT HORAN, RF SENATUS, PB WHEELER, CB LIPSON, SJ TI STEVENS-JOHNSON-TYPE REACTION WITH VANCOMYCIN TREATMENT SO ANNALS OF PHARMACOTHERAPY LA English DT Note ID RED-MAN SYNDROME; ERYTHEMA MULTIFORME AB OBJECTIVE: To report a case of Stevens-Johnson syndrome caused by vancomycin. CASE SUMMARY: Stevens-Johnson syndrome is an acute mucocutaneous process characterized by epidermal and mucosal desquamation. Its pathogenesis is poorly understood. Mortality rates have ranged from 30 to 100 percent. We describe a case of Stevens-Johnson syndrome related to the use of vancomycin in a 7 1 -year-old woman with rheumatoid arthritis receiving treatment for an infected cervical fusion site. Classic "target" lesions distributed throughout the trunk and extremities along with erosive lesions involving the oral and vaginal mucosae were observed in this patient. DISCUSSION: A number of agents have been implicated in the etiology of Stevens-Johnson syndrome. Serious cutaneous reactions to vancomycin, however, have been uncommon. Cessation of vancomycin treatment in our patient led to eventual resolution of her symptoms. CONCLUSIONS: Vancomycin is a potential causative agent of Stevens-Johnson syndrome. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT DERMATOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02215. RP LAURENCIN, CT (reprint author), MIT,DIV HLTH SCI & TECHNOL,BLDG 56,RM 141,CAMBRIDGE,MA 02139, USA. NR 20 TC 10 Z9 11 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD DEC PY 1992 VL 26 IS 12 BP 1520 EP 1521 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KC198 UT WOS:A1992KC19800006 PM 1482807 ER PT J AU MATHISEN, DJ GRILLO, HC AF MATHISEN, DJ GRILLO, HC TI CLINICAL MANIFESTATION OF MEDIASTINAL FIBROSIS AND HISTOPLASMOSIS SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 28TH ANNUAL MEETING OF THE SOC OF THORACIC SURGEONS CY FEB 03-05, 1992 CL ORLANDO, FL SP SOC THORAC SURGEONS ID VENA-CAVA SYNDROME; PULMONARY AB We treated 20 patients thought to have mediastinal fibrosis secondary to Histoplasma capsulatum. All but 1 were symptomatic. The most common symptoms were dyspnea (8), hemoptysis (6), postobstructive pneumonia (5), and superior vena caval obstruction (2). Nine patients had severe stenosis of the trachea, carina, or main bronchus. Special stains identified Histoplasma capsulatum in surgical specimens in 9 patients. Surgical procedures were done for 18 of 20 patients (resection of subcarinal mass, 6; right middle and lower lobectomy, 5; carinal pneumonectomy, 4; esophagoplasty, 4; sleeve resection, 3 (with right main bronchus in 1, right lower and middle lobectomy in 1, and carina in 1); right upper lobectomy, 1; middle lobectomy, 1; and bronchoplasty of left main bronchus, 1. There were 4 deaths, 3 after complications of carinal pneumonectomy and 1 in a patient with tracheobronchial obstruction that could not be dilated. Two patients were treated with amphotericin and 4 with ketoconazole. Sclerosing mediastinitis secondary to histoplasmosis presents tremendous surgical challenges because of the intense fibrosis encountered. Bronchoplastic procedures are possible in spite of the intense fibrosis. High mortality rates after carinal resection may be encountered. The exact role of antifungal therapy is as yet undefined. RP MATHISEN, DJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN THORAC SURG UNIT,BOSTON,MA 02114, USA. NR 17 TC 53 Z9 58 U1 0 U2 1 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 DEC PY 1992 VL 54 IS 6 BP 1053 EP 1058 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA KA693 UT WOS:A1992KA69300005 PM 1449286 ER PT J AU CRAIG, WA EBERT, SC AF CRAIG, WA EBERT, SC TI CONTINUOUS INFUSION OF BETA-LACTAM ANTIBIOTICS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Review ID KLEBSIELLA-PNEUMONIAE PNEUMONIA; ESCHERICHIA-COLI; STREPTOCOCCUS-PNEUMONIAE; EXPERIMENTAL MENINGITIS; HEMOPHILUS-INFLUENZAE; BACTERICIDAL ACTIVITY; THERAPEUTIC EFFICACY; INTERSTITIAL FLUID; CYSTIC-FIBROSIS; THIGH-INFECTION C1 UNIV WISCONSIN,SCH PHARM,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT MED,MADISON,WI 53705. MERITER HOSP,DEPT PHARM,MADISON,WI 53715. RP CRAIG, WA (reprint author), UNIV WISCONSIN,DEPT MED,MADISON,WI 53792, USA. NR 77 TC 236 Z9 241 U1 0 U2 1 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 DEC PY 1992 VL 36 IS 12 BP 2577 EP 2583 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA KA934 UT WOS:A1992KA93400001 PM 1482127 ER PT J AU HARDIN, TC SHARKEY, PK LAM, YFF WALLACE, JE RINALDI, MG GRAYBILL, JR AF HARDIN, TC SHARKEY, PK LAM, YFF WALLACE, JE RINALDI, MG GRAYBILL, JR TI PHARMACOKINETICS OF SCH-39304 IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS FOLLOWING CHRONIC ORAL DOSING SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NORMAL VOLUNTEERS; PENETRATION AB The pharmacokinetics of SCH-39304, an investigational, orally active, broad-spectrum antifungal agent, were evaluated in 17 adult, human immunodeficiency virus-positive males. Patients were studied on days 1 and 16 and were divided into the following three treatment groups: (i) patients with culture-proven oropharyngeal candidiasis who were not receiving concurrent zidovudine therapy and who were treated with 50 mg of SCH-39304 daily (n = 6); (ii) patients with culture-proven oropharyngeal candidiasis who were receiving concurrent zidovudine therapy and who were treated with 50 mg of SCH-39304 daily (n = 5); and (iii) patients with or without oropharyngeal candidiasis who were receiving concurrent zidovudine therapy and who were treated with 200 mg of SCH-39304 daily (n = 6). All patients received a single daily dose of the study medication for 16 days. Plasma samples for SCH-39304 concentration measurement were collected for 6 h following the initial dose and for 504 h following the day 16 dose. Urine was collected for 24 h following SCH-39304 administration on days 1 and 16. All samples were assayed for SCH-39304 by gas chromatography. Wide intersubject variations in SCH-39304 plasma concentration-versus-time profiles were observed on each study day. Absorption appeared to be slow, with mean day 1 peak plasma SCH-39304 concentrations of 1.2 mug/ml at 2.1 h (50 mg) and 3.9 mug/ml at 4.0 h (200 mg) after drug administration. Mean peak plasma SCH-39304 concentrations on day 16 were 7.6 mug/ml at 4.3 h (50 mg) and 17.2 mug/ml at 3.2 h (200 mg) after drug administration. Mean elimination half-lives on day 16 for the 50- and 200-mg daily dosages were 100 and 89 h, respectively. SCH-39304 was cleared primarily unchanged in the urine. Mean areas under the plasma concentration-versus-time curve (from 0 to 24 h) on day 16 reflect a lower than expected increase with the 200-mg/day regimen (314.5 mug . h/ml) compared with that for the 50-mg/day regimen (135.9 mug . h/ml), suggesting the potential for reduced bioavailability at higher dosages. No significant effect of concurrent zidovudine therapy on the kinetics of SCH-39304 was observed. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,COLL PHARM,AUSTIN,TX 78712. RP HARDIN, TC (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284, USA. FU NCRR NIH HHS [RR-01346] NR 8 TC 2 Z9 2 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 DEC PY 1992 VL 36 IS 12 BP 2790 EP 2793 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA KA934 UT WOS:A1992KA93400037 PM 1482146 ER PT J AU MACARUSO, P AF MACARUSO, P TI COGNITIVE MODELS OF SPEECH PROCESSING - PSYCHOLINGUISTIC AND COMPUTATIONAL PERSPECTIVES - ALTMANN,GTM SO APPLIED PSYCHOLINGUISTICS LA English DT Book Review RP MACARUSO, P (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0142-7164 J9 APPL PSYCHOLINGUIST JI Appl. Psycholinguist. PD DEC PY 1992 VL 13 IS 4 BP 529 EP 533 DI 10.1017/S0142716400005798 PG 5 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA KE879 UT WOS:A1992KE87900006 ER PT J AU LUI, H ANDERSON, RR AF LUI, H ANDERSON, RR TI PHOTODYNAMIC THERAPY IN DERMATOLOGY - SHEDDING A DIFFERENT LIGHT ON SKIN-DISEASE SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID BASAL-CELL CARCINOMA; TUMOR DESTRUCTION; PHOTOFRIN-II; HEMATOPORPHYRIN; CANCER; PHOTOSENSITIVITY; RECURRENCE; LESIONS; HPD C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RP LUI, H (reprint author), UNIV BRITISH COLUMBIA,DIV DERMATOL,855 W 10TH AVE,VANCOUVER V5Z 1L7,BC,CANADA. NR 30 TC 37 Z9 38 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1992 VL 128 IS 12 BP 1631 EP 1636 DI 10.1001/archderm.128.12.1631 PG 6 WC Dermatology SC Dermatology GA KC182 UT WOS:A1992KC18200009 PM 1456759 ER PT J AU ROPPER, AH COLE, D LOUIS, DN AF ROPPER, AH COLE, D LOUIS, DN TI THE BRAIN-STEM VIEWED INSITU FROM ABOVE SO ARCHIVES OF NEUROLOGY LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP ROPPER, AH (reprint author), ST ELIZABETH HOSP,DIV NEUROL,736 CAMBRIDGE ST,BOSTON,MA 02135, 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 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 1992 VL 49 IS 12 BP 1230 EP 1230 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA KA933 UT WOS:A1992KA93300003 PM 1449398 ER PT J AU SCHMAHMANN, JD AF SCHMAHMANN, JD TI THE NEUROPSYCHOLOGY OF THE CEREBELLUM - AN EMERGING CONCEPT - REPLY SO ARCHIVES OF NEUROLOGY LA English DT Letter RP SCHMAHMANN, JD (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,FRUIT ST,BOSTON,MA 02114, USA. NR 3 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 1992 VL 49 IS 12 BP 1230 EP 1230 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA KA933 UT WOS:A1992KA93300002 ER PT J AU YANNUZZI, LA SORENSON, JA SOBEL, RS DALY, JR DEROSA, JT SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA GELLES, E GONET, R BURTON, TC CULVER, J METZGER, K KALBFLEISCH, N ZARLING, D FARBER, MD BLAIR, N STELMACK, T AXELROD, A WAITR, SE CROSS, A ROLNICK, C FLOM, T HALLER, J PUSIN, S CASSEL, G APPLEGATE, CA SEIGEL, D SPERDUTO, RD HILLER, R MOWERY, R CHEW, E TAMBOLI, A MILLER, DT SOWELL, AL GUNTER, EW DUNN, M SEDDON, JM SHAMBAN, K GELLES, E LENTO, D ALEXANDER, JA PHILLIPS, DA AF YANNUZZI, LA SORENSON, JA SOBEL, RS DALY, JR DEROSA, JT SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA GELLES, E GONET, R BURTON, TC CULVER, J METZGER, K KALBFLEISCH, N ZARLING, D FARBER, MD BLAIR, N STELMACK, T AXELROD, A WAITR, SE CROSS, A ROLNICK, C FLOM, T HALLER, J PUSIN, S CASSEL, G APPLEGATE, CA SEIGEL, D SPERDUTO, RD HILLER, R MOWERY, R CHEW, E TAMBOLI, A MILLER, DT SOWELL, AL GUNTER, EW DUNN, M SEDDON, JM SHAMBAN, K GELLES, E LENTO, D ALEXANDER, JA PHILLIPS, DA TI RISK-FACTORS FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID NUTRITION EXAMINATION SURVEY; 1ST NATIONAL-HEALTH; SPECTROMETRY; MACULOPATHY; HEART; ZINC AB Neovascular age-related macular degeneration (AMD) is one of five retinal disorders studied in the Eye Disease Case-Control Study. Data were obtained from 421 patients with neovascular AMD and 615 controls on a broad array of possible risk factors through interviews, clinical examinations, and laboratory analyses of blood samples. Decreased risk of neovascular AMD was associated with higher levels of carotenoids in the serum samples, higher horizontal cup-to-disc ratios, and use of postmenopausal exogenous estrogens in women. Increased risk of neovascular AMD was associated with cigarette smoking, higher levels of serum cholesterol, and parity greater than zero. No support was found for sunlight exposure, serum zinc levels, or iris color as risk factors for this disease. Although no association was found with a history of cardiovascular disease itself, the associations with post-menopausal exogenous estrogen use, cigarette smoking, and serum cholesterol level are consistent with a hypothesis linking risk factors for cardiovascular disease with neovascular AMD. The association noted between serum carotenoid levels and neovascular AMD supports the hypothesis that higher levels of micronutrients with antioxidant capabilities may decrease the risk of AMD. C1 NEI,BIOMETRY & EPIDEMIOL PROGRAM,BLDG 31,ROOM 6A24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV ILLINOIS,CHICAGO,IL 60680. JOHNS HOPKINS UNIV HOSP,WILMER EYE INST,BALTIMORE,MD 21205. CTR DIS CONTROL,CTR ENVIRONM HLTH & HYG CONTROL,DIV ENVIRONM HLTH LAB SCI,ATLANTA,GA 30333. ORKAND CORP,CTR COORDINATING,SILVER SPRING,MD. CTR PHOTOG READING,BOSTON,MA. CTR MACULAR GRADING READING,BALTIMORE,MD. NR 23 TC 396 Z9 404 U1 4 U2 10 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 DEC PY 1992 VL 110 IS 12 BP 1701 EP 1708 PG 8 WC Ophthalmology SC Ophthalmology GA KC117 UT WOS:A1992KC11700022 ER PT J AU ROIDER, J MICHAUD, NA FLOTTE, TJ BIRNGRUBER, R AF ROIDER, J MICHAUD, NA FLOTTE, TJ BIRNGRUBER, R TI RESPONSE OF THE RETINAL-PIGMENT EPITHELIUM TO SELECTIVE PHOTOCOAGULATION SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID KRYPTON LASER PHOTOCOAGULATION; DIABETIC MACULAR EDEMA; ORGAN-CULTURE; CHOROIDAL NEOVASCULARIZATION; REPAIR; CELLS; BARRIER; INJURY AB Multiple short argon laser pulses can coagulate the retinal pigment epithelium selectively, while sparing the adjacent neural retina and choroid; in contrast, continuous-wave laser irradiation typically damages the neural retina and choroid. The healing response to selective photocoagulation of the retinal pigment epithelium was studied in rabbits during a period of 4 weeks. The lesions were never visible ophthalmoscopically. During the healing period, the epithelium was reformed by a single sheet of hypertrophic retinal pigment epithelial cells. In contrast to continuous-wave photocoagulation, only minimal inflammatory response was found. Retinal pigment epithelial cells showed clear signs of viability, eg, phagocytized outer segments. The local edema in the photoreceptor layer and subretinal space found in the early stage disappeared when the blood-retinal barrier was reestablished. The choriocapillaris remained unaffected. No subsequent damage to the photoreceptors was found. This type of photocoagulation may be useful for retinal pigment epithelium-related diseases, eg, diffuse diabetic macular edema. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. MED UNIV LUBECK,CTR MED LASER,LUBECK,GERMANY. RI Roider, Johann/E-4513-2010; Birngruber, Reginald/Q-2342-2016 NR 30 TC 118 Z9 127 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 DEC PY 1992 VL 110 IS 12 BP 1786 EP 1792 PG 7 WC Ophthalmology SC Ophthalmology GA KC117 UT WOS:A1992KC11700041 PM 1463423 ER PT J AU CLINTON, SK LIBBY, P AF CLINTON, SK LIBBY, P TI CYTOKINES AND GROWTH-FACTORS IN ATHEROGENESIS SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT 22ND CONF ON HEMOSTASIS AND ATHEROSCLEROTIC DISEASE CY APR 28-MAY 01, 1992 CL NEW ORLEANS, LA SP COLL AMER PATHOLOGISTS ID SMOOTH-MUSCLE CELLS; LOW-DENSITY-LIPOPROTEIN; COLONY-STIMULATING FACTOR; HUMAN ENDOTHELIAL-CELLS; TUMOR NECROSIS FACTOR; HERITABLE HYPERLIPIDEMIC RABBIT; MONOCYTE CHEMOTACTIC PROTEIN-1; INTERLEUKIN-1 GENE-EXPRESSION; ATHEROSCLEROTIC LESIONS; NONHUMAN PRIMATE AB The development of laboratory techniques for the culturing of vascular endothelial and smooth-muscle cells during the 1970s, followed by the rapid advances in molecular and cell biology during the 1980s, provided the foundation for the identification of growth factor and cytokine networks involved in maintenance of the normal vasculature as well as participating in diverse pathologic processes involving blood vessels.1-3 Vascular cells can produce and respond to a vast array of biochemical messengers that control cell replication, differentiation, and many specific cell functions. Investigators are beginning to explore the changes in the patterns of messengers exchanged between the vascular cells and infiltrating leukocytes during the initiation and progression of atherosclerosis. A variety of in vitro and in vivo studies have indicated that growth factors and cytokines that mediate the critical processes of inflammation and wound healing also play a central role in vascular disease. Indeed, many view atherosclerosis as the result of excessive or prolonged chronic inflammation and wound healing in response to diverse injurious stimuli to cells of the vessel wall. Vascular injury may result from many varied and interacting forces, including nutritional and metabolic abnormalities such as hyperlipidemias or elevated homocysteine, mechanical forces associated with hypertension, exogenous toxins including those found in cigarette smoke, abnormally glycated proteins associated with diabetes mellitus, oxidatively modified lipids or proteins, and, possibly, viral infections. Ultimately, a greater understanding of the activated cytokine and growth factor networks within the vascular wall following injury and during atherogenesis will allow clinical scientists to identify steps susceptible to therapeutic intervention using recombinant cytokines, antibodies, soluble receptors, or receptor antagonists. Other therapeutic strategies may involve the transfection of specific genes, which may inhibit atherosclerosis, into vascular cells at sites prone to lesion formation. C1 BRIGHAM & WOMENS HOSP,DEPT MED,VASC MED & ATHEROSCLEROSIS UNIT,BOSTON,MA 02115. RP CLINTON, SK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB 1730A,44 BINNEY ST,BOSTON,MA 02115, USA. NR 74 TC 170 Z9 171 U1 1 U2 5 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 DEC PY 1992 VL 116 IS 12 BP 1292 EP 1300 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA KD172 UT WOS:A1992KD17200005 PM 1456874 ER PT J AU GALE, GR WALKER, EM SMITH, AB JONES, MM STONE, A BASINGER, MA SINGH, PK AF GALE, GR WALKER, EM SMITH, AB JONES, MM STONE, A BASINGER, MA SINGH, PK TI N-BENZYL-N-LACTYL DITHIOCARBAMATE TREATMENT OF MICE AFTER CHRONIC CADMIUM ADMINISTRATION SO ARCHIVES OF TOXICOLOGY LA English DT Article DE CADMIUM; DITHIOCARBAMATES ID CHELATING-AGENTS; MOBILIZATION; INTOXICATION; ANTAGONISTS; EXCRETION; DEPOSITS AB Administration of N-benzyl-N-lactyl dithiocarbamate (BLDTC) to mice after chronic cadmium (Cd) administration evoked a prompt, dose-dependent reduction of the whole body burden; 75% of the retained Cd was mobilized and excreted after 20 i.p. injections of BLDTC at 1.0 mmol/kg/injection. This same dose regimen produced 71% and 98% reductions of the renal and hepatic Cd concentrations, respectively. There was no reduction by BLDTC of the endogenous level of any of seven other metals measured: iron, magnesium, selenium, copper, calcium, zinc, and manganese. Renal proximal tubular damage in mice which received Cd followed by BLDTC was much less than that observed in kidneys from mice which received Cd alone. Chronic Cd administration led to substantial epithelial vacuolar damage to renal distal tubules, and this process was not apparently reversed or antagonized by BLDTC treatment to the extent observed in proximal tubules. C1 VET AFFAIRS MED CTR,RALPH H JOHNSON DEPT,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29401. VET AFFAIRS MED CTR,JOHN L MCCLELLAN DEPT,LITTLE ROCK,AR 72205. UNIV ARKANSAS HLTH SCI,DEPT PATHOL,LITTLE ROCK,AR 72205. VANDERBILT UNIV,DEPT CHEM,NASHVILLE,TN 37235. VANDERBILT UNIV,CTR MOLEC TOXICOL,NASHVILLE,TN 37235. RP GALE, GR (reprint author), VET ADM MED CTR,RES SERV,109 BEE ST,CHARLESTON,SC 29401, USA. FU NIEHS NIH HHS [ES-02638] NR 14 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD DEC PY 1992 VL 66 IS 10 BP 713 EP 718 DI 10.1007/BF01972622 PG 6 WC Toxicology SC Toxicology GA KC852 UT WOS:A1992KC85200005 PM 1290404 ER PT J AU COHEN, DJ CLEM, MF LUTHER, M GENECOV, DG HAMEL, JD BEGIA, BC SANGALLI, M EVANS, K FLORES, J BUNEGIN, M GRAEBER, GM GROVER, FL AF COHEN, DJ CLEM, MF LUTHER, M GENECOV, DG HAMEL, JD BEGIA, BC SANGALLI, M EVANS, K FLORES, J BUNEGIN, M GRAEBER, GM GROVER, FL TI EFFECT OF SYNCHRONOUS AND ASYNCHRONOUS PULSATILE FLOW DURING LEFT, RIGHT, AND BIVENTRICULAR BYPASS SO ARTIFICIAL ORGANS LA English DT Article DE PULSATILE FLOW; VENTRICULAR ASSIST DEVICE; MYOCARDIAL OXYGEN CONSUMPTION; R-WAVE SYNCHRONIZATION; MYOCARDIAL INFARCTION; PIERCE-DONACHY VENTRICULAR ASSIST DEVICE ID LEFT HEART BYPASS; VENTRICULAR ASSIST DEVICE; CARDIOGENIC-SHOCK; PUMP; EXPERIENCE; SURVIVAL AB Ventricular assist devices augment flow from the left atrium to the aorta and/or from the right atrium to the pulmonary artery. Most devices are used in the asynchronous full-to-empty mode (asynchronous) but may also be used in a synchronous counterpulsation mode (synchronous). This study determines the optimal assist modes to reduce myocardial oxygen consumption (MVO2) and metabolism. Twelve pigs were instrumented with carotid artery and Baim coronary sinus catheters for determination of MVO2 and myocardial lactate production (LACT). Six were implanted with a Pierce-Donachy left ventricular assist device (LVAD) and 6 with both right and left ventricular assist devices (BIVAD). Two periods each of control, synchronous, and asynchronous bypass were instituted, the midanterior descending coronary artery (LAD) was ligated, and the sequence was repeated. After each period, MVO2 and LACT were determined and myocardial biopsy specimens were obtained for tissue, lactate, and ATP assay. Following LAD ligation, biopsy specimens were obtained from both the infarct and noninfarct zones of the heart. MVO2 decreased (p < 0.05) in the asynchronous BIVAD mode compared with control. MVO2 was unchanged in synchronous BIVAD or either LVAD mode. Tissue ATP and tissue lactate were unaffected by any mode of bypass. Only BIVAD in the asynchronous mode reduced MVO2. When ventricular assist devices are utilized to aid recovery of the natural heart, two devices should always be inserted to allow biventricular assist. Synchronous counterpulsation offers no advantage. C1 UNIV TEXAS,HLTH SCI CTR,DEPT SURG,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. W VIRGINIA UNIV,MED CTR,SCH MED,DEPT SURG,MORGANTOWN,WV 26506. RP COHEN, DJ (reprint author), BROOKE ARMY MED CTR,HSHE SDC,CARDIOTHORAC SURG SERV,FT SAM HOUSTON,TX 78234, USA. NR 34 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD DEC PY 1992 VL 16 IS 6 BP 614 EP 622 PG 9 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA KD657 UT WOS:A1992KD65700012 PM 1482332 ER PT J AU HUA, QX SHOELSON, SE WEISS, MA AF HUA, QX SHOELSON, SE WEISS, MA TI NONLOCAL STRUCTURAL PERTURBATIONS IN A MUTANT HUMAN INSULIN - SEQUENTIAL RESONANCE ASSIGNMENT AND C-13-ISOTOPE-AIDED 2D-NMR STUDIES OF [PHEB24-]GLY]INSULIN WITH IMPLICATIONS FOR RECEPTOR RECOGNITION SO BIOCHEMISTRY LA English DT Article ID PHENYLALANINE-B25 SIDE-CHAIN; DES-PENTAPEPTIDE-INSULIN; SECONDARY STRUCTURE; CIRCULAR-DICHROISM; ABNORMAL INSULIN; BIOLOGICAL-ACTIVITY; SHORTENED INSULIN; INVITRO POTENCY; BINDING; ANALOGS AB Insulin's mechanism of receptor binding is not well understood despite extensive study by mutagenesis and X-ray crystallography. Of particular interest are "anomalous" analogues whose bioactivities are not readily rationalized by crystal structures. Here the structure and dynamics of one such analogue (GlyB24-insulin) are investigated by circular dichroism (CD) and isotope-aided 2D-NMR spectroscopy. The mutant insulin retains near-native receptor-binding affinity despite a nonconservative substitution (PheB24-->Gly) in the receptor-binding surface. Relative to native insulin, GlyB24-insulin exhibits reduced dimerization; the monomer (the active species) exhibits partial loss of ordered structure, as indicated by CD studies and motional narrowing of selected H-1-NMR resonance. 2D-NMR studies demonstrate that the B-chain beta-turn (residues B20-23) and beta-strand (residues B24-B28) are destabilized; essentially native alpha-helical secondary structure (residues A3-A8, A13-A18, and B9-B19) is otherwise maintained. C-13-Isotope-edited NOESY studies demonstrate that long-range contacts observed between the B-chain beta-strand and the alpha-helical core in native insulin are absent in the mutant. Implications for the mechanism of insulin's interaction with its receptor are discussed. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. CHINESE ACAD SCI,BEIJING,PEOPLES R CHINA. RP HUA, QX (reprint author), HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115, USA. FU NCRR NIH HHS [1 S10 RR04862-01]; NIDDK NIH HHS [DK36836] NR 72 TC 25 Z9 27 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 1 PY 1992 VL 31 IS 47 BP 11940 EP 11951 DI 10.1021/bi00162a037 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KA483 UT WOS:A1992KA48300037 PM 1445924 ER PT J AU BAKSHANDEH, N SIEBERT, JW CABRERA, RC EIDELMAN, Y LONGAKER, M FREUND, RW GARG, HG AF BAKSHANDEH, N SIEBERT, JW CABRERA, RC EIDELMAN, Y LONGAKER, M FREUND, RW GARG, HG TI ISOLATION AND PARTIAL CHARACTERIZATION OF HYALURONAN-PROTEIN-COLLAGEN COMPLEX (HA-PC) FROM FETAL SHEEP SKIN OF DIFFERENT GESTATIONAL AGES SO BIOCHEMISTRY INTERNATIONAL LA English DT Article ID PROTEOGLYCANS; SCAR; ACID; DEGRADATION; DEPOSITION; MODEL C1 UNIV CALIF SAN FRANCISCO,FETAL TREATMENT PROGRAM,SAN FRANCISCO,CA 94143. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. RP BAKSHANDEH, N (reprint author), NYU MED CTR,INST RECONSTRUCT PLAST SURG,NEW YORK,NY 10016, USA. NR 26 TC 5 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 0158-5231 J9 BIOCHEM INT PD DEC PY 1992 VL 28 IS 5 BP 843 EP 851 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KH518 UT WOS:A1992KH51800009 PM 1288494 ER PT J AU KAHN, RS KNOTT, P GABRIEL, S DUMONT, K MASTROIANNI, L DAVIDSON, M AF KAHN, RS KNOTT, P GABRIEL, S DUMONT, K MASTROIANNI, L DAVIDSON, M TI EFFECT OF M-CHLOROPHENYLPIPERAZINE ON PLASMA HOMOVANILLIC-ACID CONCENTRATIONS IN HEALTHY-SUBJECTS SO BIOLOGICAL PSYCHIATRY LA English DT Article ID CENTRAL DOPAMINERGIC ACTIVITY; META-CHLOROPHENYLPIPERAZINE; SCHIZOPHRENIC-PATIENTS; NEURO-ENDOCRINE; HUMAN-BRAIN; HALOPERIDOL; DEBRISOQUIN; LEVEL; RAT; HVA AB In view of the abundant anatomical and functional interactions between serotonin and dopamine systems, this study examined the effect of the serotonin agonist, m-chlorophenylpiperazine (mCPP) on plasma concentrations of the dopamine metabolite, homovanillic acid. Plasma prolactin levels, body temperature, and mCPP blood level were also measured. mCPP (0.35 mg/kg) and placebo were administered orally to 10 healthy men in a randomized double-blind design. Variables were measured for 210 min after administration of capsules. mCPP raised prolactin and temperature as compared to placebo, but did not affect plasma homovanillic acid concentrations. Results suggest that mCPP does not alter dopamine function. RP KAHN, RS (reprint author), BRONX VET ADM MED CTR,MT SINAI SCH MED,DEPT PSYCHIAT,130 W KINGSBRIDGE ROAD,BRONX,NY 10468, USA. FU NIMH NIH HHS [R01 MH46957, R01 MH46436] NR 24 TC 11 Z9 11 U1 1 U2 1 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 DEC 1 PY 1992 VL 32 IS 11 BP 1055 EP 1061 DI 10.1016/0006-3223(92)90068-B PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KC872 UT WOS:A1992KC87200012 PM 1467386 ER PT J AU FISSORE, R OKEEFE, S KIESSLING, AA AF FISSORE, R OKEEFE, S KIESSLING, AA TI PURINE-INDUCED BLOCK TO MOUSE EMBRYO CLEAVAGE IS REVERSED BY COMPOUNDS THAT ELEVATE CYCLIC ADENOSINE-MONOPHOSPHATE SO BIOLOGY OF REPRODUCTION LA English DT Article ID DEPENDENT PROTEIN-KINASE; 2-CELL BLOCK; ETHYLENEDIAMINETETRAACETIC ACID; CULTURE-MEDIUM; CELL-CYCLE; INVITRO; AMP; TRANSCRIPTION; INHIBITION; EXPRESSION AB The second or third cleavage of mouse embryos from several strains of females is blocked in the presence of hypoxanthine. To begin to determine the mechanism of the block, we studied several aspects of cell metabolism in blocked embryos, including the stage of the cell cycle and the levels of transcription, translation, and protein phosphorylation. In addition, we attempted to reverse the block by transfer of cytoplasm, transfer of RNAs from dividing cells, and co-culture with compounds that elevate cAMP. Our results indicate the following: 1) that the embryos were blocked in interphase; 2) the expression of lac Z linked to SV40 promoter was depressed, but not blocked; 3) overall protein synthesis was depressed but the appearance of early embryonic proteins was not blocked; 4) overall phosphorylation of proteins was not affected; 5) microinjection of additional cytoplasm from non-blocking embryos did not reverse the block; and 6) compounds that elevate cAMP did reverse the block. Thus, the purines apparently do not prevent early embryonic gene expression or most phosphorylation events, but do inhibit a critical cell process occurring during interphase of the cell cycle that can be compensated by elevations in cAMP. C1 HARVARD UNIV,SCH MED,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HUMAN REPROD & REPROD BIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU PHS HHS [21980, 21988] NR 31 TC 18 Z9 20 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD DEC PY 1992 VL 47 IS 6 BP 1105 EP 1112 DI 10.1095/biolreprod47.6.1105 PG 8 WC Reproductive Biology SC Reproductive Biology GA JZ900 UT WOS:A1992JZ90000026 PM 1493175 ER PT J AU LEE, FJS MOSS, J LIN, LW AF LEE, FJS MOSS, J LIN, LW TI A SIMPLIFIED PROCEDURE FOR HYBRIDIZATION OF RNA BLOTS SO BIOTECHNIQUES LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP LEE, FJS (reprint author), NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892, USA. NR 4 TC 9 Z9 9 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1992 VL 13 IS 6 BP 844 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB620 UT WOS:A1992KB62000002 PM 1476734 ER PT J AU RON, D DRESSLER, H AF RON, D DRESSLER, H TI PGSTAG - A VERSATILE BACTERIAL EXPRESSION PLASMID FOR ENZYMATIC LABELING OF RECOMBINANT PROTEINS SO BIOTECHNIQUES LA English DT Note ID GLUTATHIONE-S-TRANSFERASE; LEUCINE ZIPPER PROTEINS; ESCHERICHIA-COLI; C/EBP; IDENTIFICATION; PURIFICATION; INTERACT; CLONING; FAMILY AB We report on the construction of a plasmid, pGSTag, that directs the expression in E. coli of a glutathione S-transferase fusion protein that contains a high affinity phosphorylation site by protein kinase-A (PK-A). The fusion protein, following purification from crude bacterial lysates by substrate affinity chromatography, can be labeled in vitro to high specific activity with purified PK-A and 32p-gamma-ATP. Because labeling takes place while the fusion protein is immobilized on a solid support, the unincorporated label and enzyme can be washed away. Using the leucine-zipper domains of cAMP response element binding (CREB) proteins and CCAAT/enhancer binding protein (C/EBP)-like proteins as a model system, we show that the labeled protein, after elution from the affinity resin, can be used as a probe to detect interacting (dimerizing) species in a nitrocellulose-based ligand blot assay. The utility of this system for the creation of labeled protein probes is discussed. RP RON, D (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,SCH MED,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114, USA. NR 12 TC 134 Z9 135 U1 0 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1992 VL 13 IS 6 BP 866 EP 869 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB620 UT WOS:A1992KB62000008 PM 1476738 ER PT J AU KOLAKOWSKI, LF LEUNISSEN, JAM SMITH, JE AF KOLAKOWSKI, LF LEUNISSEN, JAM SMITH, JE TI PROSEARCH - FAST SEARCHING OF PROTEIN SEQUENCES WITH REGULAR EXPRESSION PATTERNS RELATED TO PROTEIN-STRUCTURE AND FUNCTION SO BIOTECHNIQUES LA English DT Article ID PROSITE AB This report describes the implementation of ProSearch, a computer program that can efficiently search for motifs in protein sequences. ProSearch currently uses motifs that are contained in the PROSITE database, but user-developed patterns can easily be added to any search. ProSearch can generate a report identifying the patterns present in a given protein sequence, their locations and, if desired, a short description of the identified patterns. The program is written in AWK (a small interpreted computer language), which can run on all computer platforms commonly found in laboratories. ProSearch can search a 348-amino acid protein for 690 patterns in less than 5 s on a typical workstation. C1 CATHOLIC UNIV NIJMEGEN,NIJMEGEN,NETHERLANDS. UNIV PENN,PHILADELPHIA,PA 19104. RP KOLAKOWSKI, LF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,RENAL UNIT,149 13TH ST,BOSTON,MA 02129, USA. NR 8 TC 19 Z9 19 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 1992 VL 13 IS 6 BP 919 EP 921 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB620 UT WOS:A1992KB62000020 PM 1476747 ER PT J AU ANDERSON, KC MORIMOTO, C PAUL, SR CHAUHAN, D WILLIAMS, D COCHRAN, M BARUT, BA AF ANDERSON, KC MORIMOTO, C PAUL, SR CHAUHAN, D WILLIAMS, D COCHRAN, M BARUT, BA TI INTERLEUKIN-11 PROMOTES ACCESSORY CELL-DEPENDENT B-CELL DIFFERENTIATION IN HUMANS SO BLOOD LA English DT Article ID HUMAN PERIPHERAL-BLOOD; STIMULATORY FACTOR-I; T-CELL; MONOCLONAL-ANTIBODIES; LYMPHOCYTES-B; PRODUCE IMMUNOGLOBULIN; MOLECULAR-CLONING; COMPLEMENTARY-DNA; IL-6 PRODUCTION; FACTOR BCDF C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP ANDERSON, KC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA50947]; NIAMS NIH HHS [AR33713] NR 64 TC 55 Z9 55 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 DEC 1 PY 1992 VL 80 IS 11 BP 2797 EP 2804 PG 8 WC Hematology SC Hematology GA KA482 UT WOS:A1992KA48200013 PM 1450406 ER PT J AU SCHMAHMANN, JD NITSCH, RM PANDYA, DN AF SCHMAHMANN, JD NITSCH, RM PANDYA, DN TI THE MYSTERIOUS RELOCATION OF THE BUNDLE OF TURCK SO BRAIN LA English DT Article ID RHESUS-MONKEY; BASIS PONTIS; PROJECTIONS; MACAQUE AB The name bundle of Turck has become synonymous with the temporopontine tract. As details concerning this pathway have been confusing and incomplete we reviewed the papers of Ludwig Turck (1810 - 1868) to determine what in fact he originally described. Turck's pioneering degeneration studies provided great detail concerning the corticospinal tracts. Charcot recognized his contributions and used the eponym 'bundle of Turck' to denote the anterior corticospinal tract. Turck did not observe projections from the temporal lobe to the basis pontis, nor did he describe a temporopontine tract located at the most lateral aspect of the cerebral peduncle. The papers of Meynert, Flechsig and others reveal the origins of the current incorrect use of the eponym. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,NEUROL UNIT,BOSTON,MA 02215. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. EDITH NOURSE ROGERS MEM VET ADM HOSP,BEDFORD,MA 01730. RP SCHMAHMANN, JD (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,KENNEDY 905B,14 FRUIT ST,BOSTON,MA 02114, USA. FU PHS HHS [16841] NR 59 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0006-8950 J9 BRAIN JI Brain PD DEC PY 1992 VL 115 BP 1911 EP 1924 DI 10.1093/brain/115.6.1911 PN 6 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA KJ446 UT WOS:A1992KJ44600017 PM 1486468 ER PT J AU SIEFF, CA YOKOYAMA, CT ZSEBO, KM TRAMMELL, J ANDERSEN, JW NATHAN, DG WILLIAMS, DA AF SIEFF, CA YOKOYAMA, CT ZSEBO, KM TRAMMELL, J ANDERSEN, JW NATHAN, DG WILLIAMS, DA TI THE PRODUCTION OF STEEL FACTOR MESSENGER-RNA IN DIAMOND-BLACKFAN ANEMIA LONG-TERM CULTURES AND INTERACTIONS OF STEEL FACTOR WITH ERYTHROPOIETIN AND INTERLEUKIN-3 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; C-KIT PROTOONCOGENE; GROWTH-FACTOR; SI-LOCUS; ANEMIA; LIGAND; INVITRO; IDENTIFICATION; SUPPRESSION; RECEPTOR AB Diamond-Blackfan anaemia (DBA) is a congenital macrocytic anaemia. To investigate whether DBA is due to hyporesponsiveness to or hypoproduction of Steel factor (SF), we compared the in vitro responsiveness of the BFU-E contained in the Ficoll-Hypaque non-adherent cell fraction of six DBA marrows with that of four normal marrows and one transient erythroblastopenia of childhood (TEC) marrow. In addition, we studied the effect of soluble SF on long-term marrow cultures (LTMC) and analysed the stromal cells from these cultures for SF mRNA transcripts. All the patients showed an erythropoietin dose-related increase of small BFU-E. The number and size of BFU-E was increased with the addition to the epo of IL-3 or SF; IL-3 + SF was not synergistic. The addition of soluble SF to LTMC of DBA patients was associated with a small but consistent increase in non-adherent cell production and an increase in the number of progenitors. Messenger RNA from immortalized stromal cell lines of three patients and from primary bone marrow stromal cells of one patient showed the presence of expected SF transcripts by PCR analysis. These results demonstrate that this group of DBA patients responds to SF and produces SF mRNA normally, indicating that SF itself is not involved in DBA pathophysiology. The effects observed suggest that, despite the lack of evidence for a causative role, SF may prove to be effective treatment for such patients. C1 CHILDRENS HOSP MED CTR,DIV PEDIAT HEMATOL & ONCOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,HOWARD HUGHES MED INST,DEPT MED,BOSTON,MA 02115. AMGEN INC,THOUSAND OAKS,CA. CHILDRENS HOSP MED CTR,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. INDIANA UNIV,SCH MED,HERMAN B WELLS CTR PEDIAT RES,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,HOWARD HUGHES MED INST,INDIANAPOLIS,IN 46202. RP SIEFF, CA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,D-1630,44 BINNEY ST,BOSTON,MA 02115, USA. NR 33 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 1992 VL 82 IS 4 BP 640 EP 647 DI 10.1111/j.1365-2141.1992.tb06938.x PG 8 WC Hematology SC Hematology GA KD005 UT WOS:A1992KD00500002 PM 1282827 ER PT J AU MORIKAWA, E ROSENBLATT, S MOSKOWITZ, MA AF MORIKAWA, E ROSENBLATT, S MOSKOWITZ, MA TI L-ARGININE DILATES RAT PIAL ARTERIOLES BY NITRIC OXIDE-DEPENDENT MECHANISMS AND INCREASES BLOOD-FLOW DURING FOCAL CEREBRAL-ISCHEMIA SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE L-ARGININE; NITRIC OXIDE; FOCAL CEREBRAL ISCHEMIA; LASER-DOPPLER FLOWMETRY; VASODILATATION; CRANIAL WINDOW ID ISCHEMIA AB L-Arginine (greater-than-or-equal-to 30 mg kg-1, i.v.), but not D-arginine (300 mg kg-1) administered 5 min after unilateral common carotid/middle cerebral artery occlusion increased regional cerebral blood flow (rCBF) within the dorsolateral ischaemic cortex in spontaneously hypertensive rats. L-Arginine (300 mg kg-1) increased rCBF from 22 +/- 2.7 to 33 +/- 4% of baseline as measured by laser-Doppler flowmetry. This increase may explain the ability of L-arginine to reduce infarct size following focal cerebral ischaemia, as reported previously. The mechanism appears to be mediated by nitric oxide since topical L-NAME (1 muM), a nitric oxide synthase inhibitor, decreased pial arteriole calibre from 115 +/- 2.2 to 106 +/- 0.9% of baseline following L-arginine infusion (300 mg kg-1). C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE RES LAB,32 FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02114. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828] NR 12 TC 103 Z9 103 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD DEC PY 1992 VL 107 IS 4 BP 905 EP 907 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KA223 UT WOS:A1992KA22300001 PM 1281721 ER PT J AU TROP, M SCHIFFRIN, EJ CALLAHAN, R CARTER, EA AF TROP, M SCHIFFRIN, EJ CALLAHAN, R CARTER, EA TI EFFECT OF HETA-STARCH COLLOIDAL SOLUTIONS ON RETICULOENDOTHELIAL PHAGOCYTIC SYSTEM (RES) FUNCTION IN BURNED AND INFECTED-RATS SO BURNS LA English DT Article AB The biodistribution of the plasma expander colloidal solution, heta-starch (HES), has been examined in rats, subjected to thermal injury or sepsis. The ability of these solutions to alter RES phagocytic function of [Tc-99m]-sulphur colloid ([Tc-99m]SC) uptake in vivo has been examined. The biodistribution of radiolabelled HES has been determined in normal rats. The HES colloidal solution has no deleterious effect upon RES function in vivo in the thermally injured animals or the septic animals as compared to sham controls. In addition, the HES colloidal solution seemed to be distributed primarily within the liver, spleen and kidney, with a small amount residing in the lung. Thermal injury did not increase the uptake of this material by the lung. These results suggest that the use of HES in thermally injured and septic individuals has no deleterious effects on RES function, nor does it accumulate in the lungs, and, hence, should be advocated for use in these situations. C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0305-4179 J9 BURNS JI Burns PD DEC PY 1992 VL 18 IS 6 BP 463 EP 465 DI 10.1016/0305-4179(92)90178-W PG 3 WC Critical Care Medicine; Dermatology; Surgery SC General & Internal Medicine; Dermatology; Surgery GA KA217 UT WOS:A1992KA21700005 PM 1489495 ER PT J AU ROSS, DM PETEET, JR MEDEIROS, C WALSHBURKE, K RIEKER, P AF ROSS, DM PETEET, JR MEDEIROS, C WALSHBURKE, K RIEKER, P TI DIFFERENCE BETWEEN NURSES AND PHYSICIANS APPROACH TO DENIAL IN ONCOLOGY SO CANCER NURSING LA English DT Article DE DENIAL; INTERDISCIPLINARY COMMUNICATION; ONCOLOGY; COPING ID CANCER; DIAGNOSIS; MEDICINE; ILLNESS AB A psychiatrist and a psychiatric nurse interviewed 33 physicians and 94 nurses at a cancer center about their experience working with oncology patients, including their usual approach to ''denial'' seen in these patients. Most respondents viewed denial as a useful, nearly universal defense mechanism, potentially capable of interfering with treatment. Physicians described a pattern in which their patients were presented with the facts one time during diagnosis and formulation of a treatment plan, after which denial was allowed and new facts not offered unless the denial was viewed as interfering with the medical intervention. Nurses more often referred to denial as a phase, stressing the importance of honesty in dealing with patients who are prone to deny. They experienced discomfort when patients who were suffering adverse effects of treatment seemed to need greater honesty from their physicians. Discussion of these differences includes the effect of the contexts in which nurses and physicians encounter denial as well as their complementary roles in patient care, and the differential goals and values of the two professions. C1 HARVARD UNIV,DIVIN SCH EXTENS,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP ROSS, DM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 19 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD DEC PY 1992 VL 15 IS 6 BP 422 EP 428 PG 7 WC Oncology; Nursing SC Oncology; Nursing GA KD260 UT WOS:A1992KD26000006 PM 1473086 ER PT J AU JOOS, S HALUSKA, FG FALK, MH HENGLEIN, B HAMEISTER, H CROCE, CM BORNKAMM, GW AF JOOS, S HALUSKA, FG FALK, MH HENGLEIN, B HAMEISTER, H CROCE, CM BORNKAMM, GW TI MAPPING CHROMOSOMAL BREAKPOINTS OF BURKITTS T(8-14) TRANSLOCATIONS FAR UPSTREAM OF C-MYC SO CANCER RESEARCH LA English DT Article ID RENAL-CELL CARCINOMA; T-CELL; MURINE PLASMACYTOMAS; COSMID VECTOR; B-CELL; N-MYC; GENE; LOCUS; DNA; LYMPHOMAS AB To analyze the region upstream of c-myc, a number of novel probes were established. These were generated by chromosomal walking starting from the breakpoint of the chromosomal translocation of the B-cell line 380 and by cloning the breakpoint of the translocation of the Burkitt lymphoma cell line IARC/BL72. Using the newly isolated probes a detailed physical map of 500 kilobases of the region upstream of c-myc was established applying pulsed-field gel electrophoresis. The chromosomal breakpoint of IARC/BL72 cells was mapped to a site 55 kilobases 5' of c-myc. A region 20 kilobases in length and containing the breakpoints of 380, EW36, P3HR-1, and Daudi cells was identified 170-190 kilobases upstream of c-myc. In addition the HPV18 integration site in HeLa cells was located between 340 and 500 kilobases 5' of c-myc. The probes were used to define the c-myc amplification units in Colo320-HSR and HL60 cells as well as in four cases of small cell lung cancer. Evidence is provided that the amplicon of HL60 cells is discontinuously organized. C1 GSF FORSCHUNGSZENTRUM UMWELT & GESUNDHEIT GMBH,INST KLIN MOLEK BIOL & TUMOR GENET,W-8000 MUNICH 70,GERMANY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HOP NECKER ENFANTS MALAD,INSERM,U173,F-75730 PARIS,FRANCE. UNIV ULM,KLIN GENET ABT,W-7900 ULM,GERMANY. JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. NR 40 TC 59 Z9 59 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 DEC 1 PY 1992 VL 52 IS 23 BP 6547 EP 6552 PG 6 WC Oncology SC Oncology GA JZ430 UT WOS:A1992JZ43000019 PM 1330296 ER PT J AU LEUNIG, M YUAN, F MENGER, MD BOUCHER, Y GOETZ, AE MESSMER, K JAIN, RK AF LEUNIG, M YUAN, F MENGER, MD BOUCHER, Y GOETZ, AE MESSMER, K JAIN, RK TI ANGIOGENESIS, MICROVASCULAR ARCHITECTURE, MICROHEMODYNAMICS, AND INTERSTITIAL FLUID PRESSURE DURING EARLY GROWTH OF HUMAN ADENOCARCINOMA LS174T IN SCID MICE SO CANCER RESEARCH LA English DT Article ID TUMOR-CELL LINES; DORSAL SKIN FOLD; NEOPLASTIC TISSUES; VASCULAR SYSTEM; BLOOD-FLOW; TRANSPORT; CHAMBER; MICROCIRCULATION; PERMEABILITY; ANTIBODIES AB To date, most quantitative information on tumor angiogenesis, microcirculation, and transport has been derived from rodent tumors grown in transparent chamber preparations. In this paper we present a chamber technique adapted to immunodeficient mice for the study of human tumor xenografts. Microcirculatory parameters in severe combined immunodeficient mice bearing a dorsal skin fold chamber preparation were quantified using intravital microscopy and image analysis. The take rate of the human colon adenocarcinoma LS174T in the chamber preparation was 100%, and the tumor area doubling time was 6.5 days. Three days following implantation of 2 x 10(5) tumor cells onto the striated skin muscle, capillary sprouts were noted in the tumor cell mass. Microvasculature in the tumors was established after 10 days. Capillary density, vessel diameter, red blood cell velocity, and blood flow rates in individual microvessels measured on days 10, 14, 18, and 22 showed no statistical difference in the striated muscle (capillaries) and subcutaneous tissue (arterioles and venules) of the skin of tumor-free animals (N = 6), whereas these parameters increased slightly, but not significantly, in the LS174T tumors (N = 7). Mean interstitial fluid pressure (+/-SD) in these small tumors was 4.6 +/- 1.7 mmHg (N = 4) on day 10 and 5.1 +/- 0.9 mmHg (N = 4) on day 22 and significantly elevated compared to that in the subcutaneous and skin tissue (-0.9 +/- 0.8 mmHg) (N = 4) (P < 0.001). To our knowledge, this is the first model enabling intravital microscopic studies of human tumor xenografts in a transparent chamber preparation in severe combined immunodeficient mice. Studies on angiogenesis, microcirculation, and transport using such a preparation should provide new insights into microcirculation-mediated mechanisms for cancer treatment. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,STEELE LAB,BOSTON,MA 02114. UNIV MUNICH,KLINIKUM GROSSHADERN,INST SURG RES,W-8000 MUNICH 70,GERMANY. UNIV MUNICH,KLINIKUM GROSSHADERN,INST ANESTHESIOL,W-8000 MUNICH 70,GERMANY. RI Yuan, Fan/A-1287-2011; Leunig, Michael/E-7951-2017 OI Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [CA13111, CA36902, CA37239] NR 44 TC 315 Z9 318 U1 1 U2 14 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 DEC 1 PY 1992 VL 52 IS 23 BP 6553 EP 6560 PG 8 WC Oncology SC Oncology GA JZ430 UT WOS:A1992JZ43000020 PM 1384965 ER PT J AU NAKAI, H MISAWA, S TOGUCHIDA, J YANDELL, DW ISHIZAKI, K AF NAKAI, H MISAWA, S TOGUCHIDA, J YANDELL, DW ISHIZAKI, K TI FREQUENT P53 GENE-MUTATIONS IN BLAST CRISIS OF CHRONIC MYELOGENOUS LEUKEMIA, ESPECIALLY IN MYELOID CRISIS HARBORING LOSS OF A CHROMOSOME-17P SO CANCER RESEARCH LA English DT Article ID CHRONIC MYELOCYTIC-LEUKEMIA; POLYMERASE CHAIN-REACTION; CELLULAR TUMOR-ANTIGEN; CELLS; EVOLUTION; EVENTS; DNA; DELETIONS; PROTEIN; CANCERS AB We investigated chromosome alterations and mutations of the p53 gene in 118 samples from 92 patients with chronic myelogenous leukemia in various clinical phases, i.e., chronic phase, accelerated phase, and blast crisis (BC). Single-strand conformation polymorphism analysis and subsequent nucleotide sequencing disclosed no alteration of the p53 gene in chronic phase (no mutation in 80 samples), while five of 31 BC samples showed point mutations: four in myeloid and one in lymphoid crisis. One of seven accelerated phase samples also showed a p53 gene mutation. Ten of 31 BC samples showed loss of one of the short arms of chromosome 17 (17p) through the formation of isochromosome 17q, i(17q), or unbalanced translocations. Loss of heterozygosity at the p53 locus in the accelerated phase and BC was detected only in two cases with i(17q) but not in seven cases with normal chromosome 17 homologues, suggesting that loss of one p53 allele is rare without cytogenetically detectable loss of a 17p. Among those six samples with p53 gene mutations, five showed loss of a 17p cytogenetically, and only one lymphoid crisis case exhibited normal chromosome 17 homologues. Thus, mutations of the p53 gene were closely associated with myeloid crisis with loss of a 17p (four mutations in ten samples), in contrast to myeloid crisis with normal chromosome 17 homologues (zero in 13) or lymphoid crisis (one in seven). Our results also suggest that alterations of the p53 gene might occur after loss of a 17p during the course of chronic myelogenous leukemia. C1 KYOTO UNIV,FAC MED,DEPT ORTHOPED SURG,SAKYO KU,KYOTO 606,JAPAN. KYOTO UNIV,CTR RADIAT BIOL,SAKYO KU,KYOTO 606,JAPAN. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA 02114. RP NAKAI, H (reprint author), KYOTO PREFECTURAL UNIV MED,DEPT INTERNAL MED 3,KAMIKYO KU,KYOTO 602,JAPAN. NR 36 TC 97 Z9 98 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 DEC 1 PY 1992 VL 52 IS 23 BP 6588 EP 6593 PG 6 WC Oncology SC Oncology GA JZ430 UT WOS:A1992JZ43000025 PM 1423304 ER PT J AU TEICHER, BA SOTOMAYOR, EA HUANG, ZD AF TEICHER, BA SOTOMAYOR, EA HUANG, ZD TI ANTIANGIOGENIC AGENTS POTENTIATE CYTOTOXIC CANCER THERAPIES AGAINST PRIMARY AND METASTATIC DISEASE SO CANCER RESEARCH LA English DT Note ID ANGIOGENESIS INHIBITION; EXTRACELLULAR-MATRIX; CORTISONE; HEPARIN; MINOCYCLINE; MEMBRANE; MELANOMA; ACETATE; MICE AB The formation of a blood supply (angiogenesis) is critical to the growth of solid tumors. The naturally occurring steroid tetrahydrocortisol, the synthetic cyclodextrin derivative beta-cyclodextrin tetradecasulfate, and the tetracycline derivative minocycline have antiangiogenic activity. Tetrahydrocortisol and beta-cyclodextrin tetradecasulfate in a 1:1 molar ratio by continuous infusion over 14 days and minocycline administered i.p. over 14 days from day 4 to day 18 postimplantation of the Lewis lung carcinoma significantly increased the growth delay of the primary tumor after treatment with cis-diamminedichloroplatinum(II), melphalan, cyclophosphamide, Adriamycin, bleomycin, and radiation therapy administered in standard regimens. Addition of the antiangiogenic agents to treatment with the cytotoxic therapies not only reduced the number of lung metastases formed from the primary tumor but also reduced the number of large metastases. Five of 12 animals treated with the antiangiogenic modulators and cyclophosphamide were long-term; survivors (>120 days). Thus, antiangiogenic therapies can potentiate the efficacy of standard anticancer therapies. C1 CHILDRENS HOSP MED CTR,BOSTON,MA 02115. RP TEICHER, BA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01-CA38493] NR 30 TC 239 Z9 250 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 DEC 1 PY 1992 VL 52 IS 23 BP 6702 EP 6704 PG 3 WC Oncology SC Oncology GA JZ430 UT WOS:A1992JZ43000045 PM 1384969 ER PT J AU SCHECTER, A RYAN, JJ CONSTABLE, JD AF SCHECTER, A RYAN, JJ CONSTABLE, JD TI PARTITIONING OF DIOXIN AND DIBENZOFURAN CONGENERS BETWEEN PLASMA AND CELL-FRACTIONS OF BLOOD FROM 10 ADULT MALE-PATIENTS SO CHEMOSPHERE LA English DT Article ID HUMAN ADIPOSE-TISSUE; MASS-SPECTROMETRIC ANALYSIS; VIETNAM VETERANS; PCDDS; PCDFS; SERUM; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; SAMPLES AB We previously characterized levels of dioxin and dibenzofuran congeners in adipose tissue and plasma fraction of blood collected from 20 adult males, using paired specimens. It has been found that the 2,3,7,8-TCDD level reported on a lipid basts was similar, although not identical, in plasma lipid and in adipose tissue lipid from the same patients, however, higher levels of the more chlorinated dioxins and dibenzofurans existed in plasma lipid as compared to adipose tissue lipid. This study reports measurements from ten individuals' blood cell fraction and compares this to the plasma fraction and to adipose tissue lipid. In all cases where readily detectable amounts of PCDD/Fs were found, a minimum of 85% was in the plasma fraction and less than 15% in the cellular component. Congeners varied in percentage for each component. C1 HLTH & WELF CANADA,OTTAWA K1A 0L2,ONTARIO,CANADA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RP SCHECTER, A (reprint author), SUNY HLTH SCI CTR,COLL MED,DEPT PREVENT MED,88 ALDRICH AVE,BINGHAMTON,NY 13903, USA. NR 13 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD DEC PY 1992 VL 25 IS 12 BP 2017 EP 2022 DI 10.1016/0045-6535(92)90039-T PG 6 WC Environmental Sciences SC Environmental Sciences & Ecology GA KG110 UT WOS:A1992KG11000025 ER PT J AU FUSTER, V BADIMON, JJ BADIMON, L AF FUSTER, V BADIMON, JJ BADIMON, L TI CLINICAL-PATHOLOGICAL CORRELATIONS OF CORONARY-DISEASE PROGRESSION AND REGRESSION SO CIRCULATION LA English DT Review DE CORONARY ARTERY DISEASE; LIPIDS; LIPOPROTEINS ID SMOOTH-MUSCLE CELLS; HIGH-DENSITY-LIPOPROTEIN; ACUTE MYOCARDIAL-INFARCTION; PORCINE VONWILLEBRAND DISEASE; SCANNING ELECTRON-MICROSCOPY; UNSTABLE ANGINA-PECTORIS; SUDDEN ISCHEMIC DEATH; FACTOR-LIKE PROTEIN; GROWTH-FACTOR; HEART-DISEASE AB The initiation of atherosclerosis may result from blood How oscillatory shear stress in certain vascular sites (bending points, bifurcations, etc.) producing chronic minimal injury resulting in functional alteration of the arterial endothelium type I injury; experimentally, this is potentiated by atherogenic risk factors such as hypercholesterolemia, hypertension, immunocomplexes, viral infections, and tobacco smoke. Such minimal injury leads to accumulation of lipid and monocytes (macrophages), and subsequently, toxic products released by the macrophages produce damage of the intimal surface with denuding endothelium type II injury or damage, which attracts platelets; all of these cells release growth factors, prompting migration and proliferation of smooth muscle cells and producing a "fibro-intimal lesion" or the outside of the capsule of a predominant "lipid lesion." The lipid lesions surrounded by a thin capsule tend to be small and rupture easily, causing type III injury or damage; that is, they are soft and weak, contain large numbers of macrophages, which may release collagenase and elastase to form abscesses, and by their location, are under the effect of flow shear forces. After plaque disruption there is thrombus formation; when thrombi are small, they can become organized and contribute to the growth of the atherosclerotic plaque; when thrombi are large and occlusive, they lead to the acute coronary syndromes. New data suggest that, at the time of plaque disruption, certain "thrombogenic" risk factors modulate the degree of thrombogenicity and, thereby, the growth of the plaque versus the various acute coronary syndromes. Aside from the need for better understanding of the basic biology of atherogenesis, emphasis on identifying and modifying the primary atherogenic and thrombogenic risk factors should continue for primary prevention. Also, new approaches should focus on the identification, stabilization, and regression of the small "lipid plaques" prone to rupture (these are not necessarily angiographically apparent), as well as on the use of better and safer antithrombotic agents for prevention of progression. RP FUSTER, V (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,JACKSON BLDG,ROOM 1328,32 FRUIT ST,BOSTON,MA 02114, USA. RI BADIMON, LINA/O-4711-2014; Fuster, Valentin/H-4319-2015 OI BADIMON, LINA/0000-0002-9162-2459; Fuster, Valentin/0000-0002-9043-9986 NR 114 TC 81 Z9 84 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1992 VL 86 IS 6 SU S BP 1 EP 11 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KB721 UT WOS:A1992KB72100001 ER PT J AU BADIMON, L CHESEBRO, JH BADIMON, JJ AF BADIMON, L CHESEBRO, JH BADIMON, JJ TI THROMBUS FORMATION ON RUPTURED ATHEROSCLEROTIC PLAQUES AND RETHROMBOSIS ON EVOLVING THROMBI SO CIRCULATION LA English DT Review DE ATHEROSCLEROSIS; THROMBUS ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; INCREASED PLASMA-LEVEL; DAMAGED VESSEL WALL; COLLAGEN TYPE-I; VONWILLEBRAND-FACTOR; UNSTABLE ANGINA; PLATELET DEPOSITION; CIGARETTE-SMOKING; SHEAR RATE AB Angiography in patients with unstable angina or myocardial infarction with subtotal coronary occlusion often reveals eccentric stenoses with irregular borders, suggesting ruptured atherosclerotic plaques and thrombosis, as documented by angioscopy and at autopsy. We have simulated and studied these processes in an ex vivo perfusion chamber and in an in vivo swine model. Our results suggest that specific local factors at the time of plaque disruption influence the degree of thrombogenicity, the stability of the growing thrombus, and, therefore, possibly also the various clinical syndromes. These factors can be divided into two groups: local vessel wall-related factors and systemic factors with local action at the area of risk. These factors include the following. 1) Exposed substrate-related effects: Plaque rupture produces a rough surface and stimulates the development of occlusive thrombus in proportion to the degree of damage. 2) Fluid dynamics-related factors: The more severe the stenotic lesion after plaque rupture, the higher the local shear rate, resulting in enhanced platelet deposition and thrombus formation. 3) Vasoconstrictive effects: Vasospasm is an important contributor to the pathogenesis of ischemic heart disease. 4) Systemic factors: There is clinical and experimental evidence to suggest that various systemic factors at the time of plaque rupture may enhance thrombogenicity (i.e., levels of epinephrine, levels of serum cholesterol, impaired fibrinolysis). We have investigated the role of residual thrombus on the process of rethrombosis and found that a residual thrombus is a very thrombogenic surface that may significantly contribute to reocclusion even in heparinized blood. Using recombinant hirudin as a pharmacological tool in our flow studies, we observed that rethrombosis is partially caused by thrombin bound to fibrin in the original thrombus, because the effect is abolished by the specific thrombin inhibitor. C1 MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. RP BADIMON, L (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,JACKSON BLDG,ROOM 1328,32 FRUIT ST,BOSTON,MA 02114, USA. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 99 TC 101 Z9 102 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 DEC PY 1992 VL 86 IS 6 SU S BP 74 EP 85 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KB721 UT WOS:A1992KB72100011 ER PT J AU BADIMON, JJ FUSTER, V BADIMON, L AF BADIMON, JJ FUSTER, V BADIMON, L TI ROLE OF HIGH-DENSITY-LIPOPROTEINS IN THE REGRESSION OF ATHEROSCLEROSIS SO CIRCULATION LA English DT Article DE ATHEROSCLEROSIS; CHOLESTEROL; LIPOPROTEINS; LIPIDS ID CORONARY HEART-DISEASE; APOLIPOPROTEIN-A-I; REVERSE CHOLESTEROL TRANSPORT; MOUSE ADIPOSE-CELLS; ENDOTHELIAL-CELLS; BINDING-PROTEIN; C-III; EFFLUX; MACROPHAGES; DEFICIENCY AB Atherosclerosis is a slowly progressive disease characterized by the accumulation of cholesterol within the vessel wall. Plasma lipoproteins are particles of complex lipid and protein composition that transport lipids in blood. Low density lipoproteins (LDL) and high density lipoproteins (HDL) are the major cholesterol-carrier lipoproteins. LDL seem to be responsible for the delivery of lipids (cholesterol) from the liver to the tissues. Compelling evidence supports the concept that the lipids deposited in the arteriosclerotic lesions are derived primarily from plasma LDL. The term "reverse cholesterol transport" describes the transport of cholesterol from extrahepatic tissues to the liver, where it may be metabolized. Reverse cholesterol transport seems to be the major route for removal of the exchangeable cholesterol deposited in the extrahepatic tissue. It has been postulated that a major role of the plasma HDL particle is to act as a scavenger of tissue cholesterol. The hypothesis that high levels of plasma HDL are protective against coronary artery disease (CAD) was initially proposed by Barr et al in the early 1950s, but it was overlooked until confirmed by the Tromso and Framingham studies in 1977, which showed an inverse relation between HDL plasma levels and incidence of CAD. Similar observations have been made in 15 major experimental studies including eight countries. Several lines of investigation suggest and/or corroborate this hypothesis, including 1) studies in tissue culture systems demonstrating plasma HDL as the preferential acceptor of cholesterol from the nonhepatic cells; 2) results from several clinical trials of lipid-lowering drugs in which an increase in HDL cholesterol was associated with a reduced incidence of CAD and a reduction in the rate of progression of the disease; 3) genetic mutations observed in certain kindreds, which are responsible for markedly high or low levels of HDL associated with resistance or earlier development of CAD, respectively; and 4) interventional animal experiments in which HDL administration not only inhibited the development but even reduced the progression of atherosclerotic lesions in rabbits. RP BADIMON, JJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,JACKSON BLDG,ROOM 1328,32 FRUIT ST,BOSTON,MA 02114, USA. RI BADIMON, LINA/O-4711-2014; Fuster, Valentin/H-4319-2015 OI BADIMON, LINA/0000-0002-9162-2459; Fuster, Valentin/0000-0002-9043-9986 NR 52 TC 91 Z9 93 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1992 VL 86 IS 6 SU S BP 86 EP 94 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KB721 UT WOS:A1992KB72100012 ER PT J AU CHESEBRO, JH WEBSTER, MWI ZOLDHELYI, P ROCHE, PC BADIMON, L BADIMON, JJ AF CHESEBRO, JH WEBSTER, MWI ZOLDHELYI, P ROCHE, PC BADIMON, L BADIMON, JJ TI ANTITHROMBOTIC THERAPY AND PROGRESSION OF CORONARY-ARTERY DISEASE - ANTIPLATELET VERSUS ANTITHROMBINS SO CIRCULATION LA English DT Article DE ANTIPLATELET THERAPY; THROMBOSIS; CORONARY ARTERY DISEASE ID TISSUE PLASMINOGEN-ACTIVATOR; ACUTE MYOCARDIAL-INFARCTION; INTRAVENOUS STREPTOKINASE; FUNCTIONAL-PROPERTIES; HEPARIN-ANTITHROMBIN; PLATELET DEPOSITION; THROMBIN INHIBITION; RECOMBINANT HIRUDIN; VESSEL WALL; PIG MODEL AB Coronary artery disease develops and progresses over decades with lipid incorporation and coalescence into the arterial wall, leading to recurrent plaque disruption, thrombosis, and organization into fibromuscular lesions. The role of thrombin in arterial thrombosis is documented by observations that specific thrombin inhibition can completely prevent intraluminal mural thrombus in vivo, even though other factors that activate platelets are not inhibited. Platelet-rich thrombi associated with deep injury have a high thrombin content and require blood levels of specific thrombin inhibition with hirudin that are eight to 10 times those required to prevent thrombi associated with lesser injury or stasis. Total prevention of mural thrombus in deeply injured arteries is impossible with aspirin or conventional antithrombotic therapy, which can reduce occlusive thrombus. Thus, conventional antithrombotic therapies can reduce clinical events but are not effective in reducing progression of coronary artery disease. Whether newer antithrombins that can totally prevent mural thrombus after deep injury can be developed and administered orally and chronically without high risk of bleeding and will be able to reduce progression of coronary artery disease is unknown. Lesion growth, vascular injury, acute coronary syndromes, and principles of thrombus formation on ruptured plaque are discussed elsewhere in this issue. This article extends these findings and discusses the prevention and treatment of mural thrombosis, the pivotal role of thrombin in arterial thrombosis, and antithrombotic therapy for the prevention and the progression of coronary artery disease. C1 MAYO CLIN & MAYO FDN,DIV CARDIOVASC DIS & INTERNAL MED,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DIV HEMATOPATHOL,ROCHESTER,MN 55905. RP CHESEBRO, JH (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,JACKSON 1401,32 FRUIT ST,BOSTON,MA 02114, USA. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 NR 68 TC 74 Z9 76 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1992 VL 86 IS 6 SU S BP 100 EP 111 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KB721 UT WOS:A1992KB72100014 ER PT J AU HAJJAR, RJ GWATHMEY, JK AF HAJJAR, RJ GWATHMEY, JK TI CROSS-BRIDGE DYNAMICS IN HUMAN VENTRICULAR MYOCARDIUM - REGULATION OF CONTRACTILITY IN THE FAILING HEART SO CIRCULATION LA English DT Article DE CALCIUM; MYOFILAMENTS; CARDIOMYOPATHY; CROSS-BRIDGE KINETICS ID RAT CARDIAC-MUSCLE; TENSION RESPONSES; HYPERTROPHIC CARDIOMYOPATHY; CROSSBRIDGE KINETICS; SKINNED TRABECULAE; BARIUM CONTRACTURE; PAPILLARY-MUSCLES; CA-2+ SENSITIVITY; SARCOMERE LENGTH; FORCE GENERATION AB Background. To investigate whether altered cross-bridge kinetics contribute to the contractile abnormalities observed in heart failure, we determined the mechanical properties of cardiac muscles from control and myopathic hearts. Methods and Results. Muscle fibers from normal (n=5) and dilated cardiomyopathy (n=6) hearts were obtained and chemically skinned with saponin. The muscles were then maximally activated at saturating calcium concentrations. Unloaded shortening velocities (V0) were determined in both groups. V0 in control was 0.72+/-0.09 L(max)/sec, whereas in myopathic muscles, V0 was 0.41+/-0.06 L(max)/sec at 22-degrees-C. The muscles were also sinusoidally oscillated at frequencies ranging between 0.01 and 100 Hz. The dynamic stiffness of the muscles was calculated from the ratio of force response amplitude to length oscillation amplitude. At low frequencies (< 0.2 Hz) the stiffness was constant but was larger in myopathic muscles. In the range of 0.2-1 Hz, there was a drop in the magnitude of dynamic stiffness to approximately one quarter of the low-frequency baseline. This range reflects cross-bridge turnover kinetics. In control muscles, the frequency of minimum stiffness was 0.78+/-0.06 Hz, whereas it was 0.42+/-0.07 Hz in myopathic muscles. At higher frequencies, the dynamic stiffness increased and reached a plateau at 30 Hz. There were no differences in the plateau reached between control and myopathic muscles. Conclusions. Because myopathic hearts have a markedly diminished energy reserve, the slowing of the cross-bridge cycling rate plays an important adaptational role in the observed contractility changes in human heart failure. Although the potential to generate maximal Ca2+-activated force is similar in normal and myopathic hearts, alterations in contractile protein composition could explain the diminished cross-bridge cycling rate in failing hearts. C1 BETH ISRAEL HOSP,HARVARD THORNDIKE LAB,DEPT MED,DIV CARDIOVASC,330 BROOKLINE AVE,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,DEPT MOLEC & CELLULAR PHYSIOL,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,INST STUDY TREATMENTS CARDIOVASC DIS,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-39091, HL-36797] NR 52 TC 63 Z9 63 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1992 VL 86 IS 6 BP 1819 EP 1826 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA KB491 UT WOS:A1992KB49100016 PM 1451254 ER PT J AU ISHIHARA, K ZILE, MR NAGATSU, M NAKANO, K TOMITA, M KANAZAWA, S CLAMP, L DEFREYTE, G CARABELLO, BA AF ISHIHARA, K ZILE, MR NAGATSU, M NAKANO, K TOMITA, M KANAZAWA, S CLAMP, L DEFREYTE, G CARABELLO, BA TI CORONARY BLOOD-FLOW AFTER THE REGRESSION OF PRESSURE-OVERLOAD LEFT-VENTRICULAR HYPERTROPHY SO CIRCULATION RESEARCH LA English DT Article DE CORONARY CIRCULATION; VENTRICULAR HYPERTROPHY; PRESSURE OVERLOAD ID AORTIC-VALVE REPLACEMENT; CARDIAC-HYPERTROPHY; HYPERTENSIVE RATS; STENOSIS; CIRCULATION; DOGS; HEARTS; ABNORMALITIES; DETERMINANTS; VASODILATION AB Abnormal coronary blood flow (CBF) in long-standing left ventricular (LV) pressure-overload hypertrophy has been associated with ischemia and LV dysfunction. Thus, goals of therapy in pressure overload are not only the relief of the overload itself but also regression in hypertrophy and subsequent improvement in CBF. However, little is known about CBF in humans or in large mammals after the relief of pressure overload, when the hypertrophy has regressed. This study was performed to test the hypothesis that, even 6 months after the relief or pressure overload in the dog, CBF would still be abnormal. Three groups of dogs were studied: 1) normal control dogs (NL group), 2) dogs with LV pressure-overload hypertrophy (LVH group), and 3) dogs that had developed LV pressure-overload hypertrophy but in whom the pressure overload was relieved 6 months before the final study (LVH Reg group). CBF was studied in conscious dogs by use of the radiolabeled microsphere technique at rest, during rapid atrial pacing, and during maximum coronary vasodilation produced by adenosine infusion. The ratio of LV weight (g) to body weight (kg) (LVBW) was 4.2 +/- 0.3 in the NL group, 7.1 +/- 0.6 in the LVH group, and 7.7 +/- 0.5 in the LVH Reg group before pressure-overload relief (p=NS, LVH versus LVH Reg). Six months after removal of the pressure overload, the LVBW in the LVH Reg group had fallen to 5.5 +/- 0.3 (p<0.05), but this LVBW was still greater than that in the NL group (p<0.05). During rapid atrial pacing, endocardial and epicardial CBF rose significantly in NL dogs. However, during rapid atrial pacing, endocardial CBF fell from 1.18 +/- 0.22 to 0.7 +/- 0.20 ml/min per gram in the LVH group (p<0.05) and did not rise in the LVH Reg group. During adenosine infusion, endocardial blood flow increased in NL dogs from 1.6.3 +/- 0.13 to 4.0 +/- 0.3 ml/min per gram and increased to a similar level in the LVH Reg group. Although CBF increased during adenosine infusion in the LVH group, the increase was less than that in the NL or LVH Reg group (p<0.05). Minimum coronary vascular resistance was similar in NL dogs (14 +/- 2 units) and LVH Reg dogs (18 +/- 3 units,p=NS) but was significantly elevated (32 +/- 10 units) in LVH dogs (p<0.05). We conclude that after significant but incomplete regression of pressure-overload hypertrophy, maximum CBF and minimum coronary vascular resistance return to normal. However, during rapid atrial pacing, significant abnormalities in CBF still exist. C1 MED UNIV S CAROLINA,DEPT MED,DIV CARDIOL,171 ASHLEY AVE,CHARLESTON,SC 29425. MED UNIV S CAROLINA,RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29425. MED UNIV S CAROLINA,GAZES,CARDIAC RES INST,CHARLESTON,SC 29425. NR 34 TC 11 Z9 12 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD DEC PY 1992 VL 71 IS 6 BP 1472 EP 1481 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA JZ072 UT WOS:A1992JZ07200020 PM 1423939 ER PT J AU TREDGET, EE SHANKOWSKY, HA JOFFE, AM INKSON, TI VOLPEL, K PARANCHYCH, W KIBSEY, PC ALTON, JDM BURKE, JF AF TREDGET, EE SHANKOWSKY, HA JOFFE, AM INKSON, TI VOLPEL, K PARANCHYCH, W KIBSEY, PC ALTON, JDM BURKE, JF TI EPIDEMIOLOGY OF INFECTIONS WITH PSEUDOMONAS-AERUGINOSA IN BURN PATIENTS - THE ROLE OF HYDROTHERAPY SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GRAM-NEGATIVE BACILLI; ESCHERICHIA-COLI; OUTBREAK; ENVIRONMENT; VIRULENCE; PROTEINS; DISEASE; INJURY; WATER; UNIT AB Pseudomonas aeruginosa remains a cause of serious wound infection and mortality in bum patients. By means of restriction fragment length polymorphism analysis and a DNA probe for the pilin gene of Pseudomonas, a lethal strain of nosocomial P. aeruginosa was identified as the cause of an outbreak of wound infections among bum patients. Environmental surveys suggested an association of the outbreak with hydrotherapy provided to many patients in a common facility. In a trial of burn wound care without hydrotherapy, overall mortality was reduced significantly, mortality associated with pseudomonas sepsis was eliminated, and the strain of P. aeruginosa associated with earlier mortality was eradicated. Moreover, fewer nosocomial pseudomonas infections, lower levels of pseudomonas resistance to aminoglycoside antibiotics, significantly fewer pseudomonas infections of skin graft donor sites, and later appearance of Pseudomonas species in burn patients were found during the period when hydrotherapy was not used. C1 UNIV ALBERTA HOSP,DEPT MICROBIOL & INFECT DIS,DIV MED MICROBIOL,EDMONTON T6G 2B7,ALBERTA,CANADA. UNIV ALBERTA,DEPT MICROBIOL,EDMONTON T6G 2E1,ALBERTA,CANADA. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP TREDGET, EE (reprint author), UNIV ALBERTA HOSP,DEPT SURG,DIV PLAST SURG,FIREFIGHTERS BURN TREATMENT UNIT,EDMONTON T6G 2B7,ALBERTA,CANADA. NR 44 TC 74 Z9 76 U1 0 U2 2 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 DEC PY 1992 VL 15 IS 6 BP 941 EP 949 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JZ600 UT WOS:A1992JZ60000006 PM 1457665 ER PT J AU RAVNIKAR, VA AF RAVNIKAR, VA TI HORMONAL MANAGEMENT OF OSTEOPOROSIS SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article ID POSTMENOPAUSAL BONE LOSS; SALMON-CALCITONIN; CALCIUM SUPPLEMENTATION; REPLACEMENT THERAPY; ESTROGEN THERAPY; SODIUM-FLUORIDE; FRACTURES; WOMEN; HIP; RISK C1 MASSACHUSETTS GEN HOSP,GYNECOL INFERTIL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,VINCENT MEM GYNECOL SERV,MENOPAUSE UNIT,BOSTON,MA 02114. RP RAVNIKAR, VA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 37 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD DEC PY 1992 VL 35 IS 4 BP 913 EP 922 DI 10.1097/00003081-199212000-00025 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA JZ585 UT WOS:A1992JZ58500023 PM 1451374 ER PT J AU ENGH, CA OCONNOR, D JASTY, M MCGOVERN, TF BOBYN, JD HARRIS, WH AF ENGH, CA OCONNOR, D JASTY, M MCGOVERN, TF BOBYN, JD HARRIS, WH TI QUANTIFICATION OF IMPLANT MICROMOTION, STRAIN SHIELDING, AND BONE-RESORPTION WITH POROUS-COATED ANATOMIC MEDULLARY LOCKING FEMORAL PROSTHESES SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID HIP-REPLACEMENT; COMPONENTS; FEMUR AB Fourteen femora containing porous-coated anatomic medullary locking (AML) femoral prostheses were retrieved from 12 patients at autopsy. Clinical roentgenograms in 13 femora showed bone remodeling changes, indicating that the implants were fixed by osseointegration. Under simulated physiologic loading, micromotion between the implant and the bone was measured using electrical displacement transducers connected to the implant and to the adjacent cortex. The micromotion between the implants at the areas of porous coating and the adjacent cortex in the one case of failed bone ingrowth measured 150 mum. Maximum relative motion between the cortex and the implant in the areas of porous coating for the 13 cases showing signs of bone ingrowth was 40 mum, and this was completely elastic relative displacement. With all implants, the micromotion between the cortex and the stem was always greatest over the uncoated portion of the stem. Four of the implants were proximally porous coated. With these, the micromotion was greater over the uncoated areas than with more extensively coated stems and was always greatest at the uncoated tip of the prosthesis. The amount of micromotion was directly related to the extent of porous coating on the implant. Maximum tip motion for the proximally coated implants was 210 micra, whereas for the fully porous-coated implants, it was 40 mum. In nine of the autopsies, the contralateral normal femur was obtained in addition to the femur containing the AML (the in vivo remodeled femur). These were used for comparative studies of strain shielding and femoral remodeling. Cortical strains were measured in the in vivo remodeled femora and were compared with measurements made in the contralateral normal femora before and following implantation of a stem identical to that present on the clinically treated side. The data showed major strain reductions in all the postmortem implanted normal femora. Comparison of the strain data from the postmortem implanted normal femora with those from the in vivo remodeled femora clearly indicated that extensive bone remodeling did not result in restoration of cortical strain levels anywhere near normal. Strain shielding continued to exist in all of the remodeled specimens, even up to 7.5 years after surgery. This strain shielding was associated with bone remodeling changes that resulted in regional reductions in bone mineral content that ranged from 7% to 78%. These observations are unique, important, and valuable in defining the in vivo function and clinical behavior of this type of porous-coated femoral component. C1 ANDERSON ORTHOPAED RES INST,ARLINGTON,VA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20057. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 28 TC 154 Z9 158 U1 0 U2 8 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 DEC PY 1992 IS 285 BP 13 EP 29 PG 17 WC Orthopedics; Surgery SC Orthopedics; Surgery GA KB632 UT WOS:A1992KB63200005 PM 1446429 ER PT J AU HARRIS, WH AF HARRIS, WH TI IS IT ADVANTAGEOUS TO STRENGTHEN THE CEMENT METAL INTERFACE AND USE A COLLAR FOR CEMENTED FEMORAL COMPONENTS OF TOTAL HIP REPLACEMENTS SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID CALCAR CONTACT; FIXATION; IMPLANT AB The mechanism of initiation of loosening of cemented femoral components is now known. It is debonding at the cement-metal interface. Current data strongly support the concept that a collar and improvement of the cement-metal interface are valuable. Precoating and having a roughened surface proximally and distally on the stem contribute to extended longevity of the cement-metal interface. Using contemporary instrumentation, collar-calcar contact can be achieved regularly and, once achieved, is well maintained for years. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114. RP HARRIS, WH (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,32 FRUIT ST,BOSTON,MA 02114, USA. NR 32 TC 70 Z9 70 U1 0 U2 2 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 DEC PY 1992 IS 285 BP 67 EP 72 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA KB632 UT WOS:A1992KB63200011 PM 1446456 ER PT J AU JASTY, M JIRANEK, W HARRIS, WH AF JASTY, M JIRANEK, W HARRIS, WH TI ACRYLIC FRAGMENTATION IN TOTAL HIP REPLACEMENTS AND ITS BIOLOGICAL CONSEQUENCES SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID CEMENTED FEMORAL COMPONENTS; 10-YEAR FOLLOW-UP; BONE-RESORPTION; ARTHROPLASTIES; MICE AB Loosening of total joint prostheses is in part related to the fragmentation of the acrylic cement mantle surrounding the prosthesis and the biologic consequences to the particulate acrylic. Fractographic studies of femoral cement mantles retrieved at revision surgery and autopsy showed frequent fractures in varying stages of development in the cement and wear at the fracture surfaces. Defects in the cement mantle, thin mantles, sharp corners on the prosthesis, separation at the cement mantle interface, and pores in the cement were frequently associated with cement fractures. The progressive fractures and wear led to the liberation of particulate acrylic debris into the surrounding tissues. The tissues at the bone-cement interface removed at revision surgery showed that a macrophage, giant-cell foreign-body granulomatous reaction occurs in response to the particulate, but not bulk cement. This tissue can produce a variety of chemical mediators of inflammation and bone resorption, and can resorb bone in organ cultures. A granulomatous tissue reaction with a verv similar appearance can be produced in experimental animals using particulate-form polymethylmethacrylate (PMMA), but not the bulk form of PMMA. The tissue reaction is not mediated by the classic cell or humeral immune mechanisms. Subcutaneous injection of particulate PMMA powder into fully immunocompetent C3Hf/SED mice as well as three strains of mice with progressive immunologic deficiencies (nude/nude, SCID, and triple deficient Nu-bg-XID/SED mice) led to a foreign-body reaction in all strains at five weeks as shown by histologic and immunohistochemical examination despite the differences in immune deficiency. This, along with the scarcity of lymphocytes in the human tissues, suggests that the biologic reactions to fragmented cement can be produced and sustained by nonimmune phagocytosis and activation by macrophages and giant cells without significant contribution by the immune system. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,HIP & IMPLANT UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP JASTY, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,ORTHOPAED BIOMECH LAB,BOSTON,MA 02114, USA. NR 32 TC 44 Z9 45 U1 1 U2 2 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 DEC PY 1992 IS 285 BP 116 EP 128 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA KB632 UT WOS:A1992KB63200016 PM 1446427 ER PT J AU BEARDEN, D ALLMAN, R SUNDARUM, V BURST, N BARTOLUCCI, A AF BEARDEN, D ALLMAN, R SUNDARUM, V BURST, N BARTOLUCCI, A TI AGE-RELATED VARIABILITY IN THE USE OF CARDIOVASCULAR PROCEDURES SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL 35233. BIRMINGHAM VAMC,BIRMINGHAM,AL. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD DEC PY 1992 VL 40 IS 4 BP A810 EP A810 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE141 UT WOS:A1992KE14100211 ER PT J AU GERACI, JM ASHTON, CM WRAY, NP WUN, CC WU, L BUSH, GW AF GERACI, JM ASHTON, CM WRAY, NP WUN, CC WU, L BUSH, GW TI COMPLICATIONS DURING HOSPITALIZATION FOR CONGESTIVE-HEART-FAILURE, CHRONIC OBSTRUCTIVE LUNG-DISEASE, OR DIABETES-MELLITUS IN VETERANS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 HOUSTON VAMC,GEN MED SECT,HOUSTON,TX. HOUSTON VAMC,MSR&D FIELD PROGRAM,HOUSTON,TX. BAYLOR COLL MED,HOUSTON,TX 77030. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD DEC PY 1992 VL 40 IS 4 BP A810 EP A810 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE141 UT WOS:A1992KE14100212 ER PT J AU GRANDALIANO, G BISWAS, P CHOUDHURY, GG BARNES, J WOODRUFF, K ABBOUD, H AF GRANDALIANO, G BISWAS, P CHOUDHURY, GG BARNES, J WOODRUFF, K ABBOUD, H TI PGE1 ANALOG MISOPROSTOL INHIBITS THROMBIN-INDUCED DNA-SYNTHESIS AND PDGF B-CHAIN GENE-EXPRESSION IN CULTURED HUMAN MESANGIAL CELLS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. VET ADM MED CTR,SAN ANTONIO,TX. RI Grandaliano, Giuseppe/G-2963-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD DEC PY 1992 VL 40 IS 4 BP A830 EP A830 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE141 UT WOS:A1992KE14100319 ER PT J AU MULROW, CD GERETY, MB LAWRENCE, VA CORNELL, JE KANTEN, DN AF MULROW, CD GERETY, MB LAWRENCE, VA CORNELL, JE KANTEN, DN TI CROSS-SECTIONAL RELATIONSHIPS BETWEEN DISEASE AND FUNCTIONAL STATUS SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD DEC PY 1992 VL 40 IS 4 BP A869 EP A869 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE141 UT WOS:A1992KE14100522 ER PT J AU WILLIAMS, JW KERBER, C MULROW, CD GERETY, MB AGUILAR, C AF WILLIAMS, JW KERBER, C MULROW, CD GERETY, MB AGUILAR, C TI DIAGNOSING MILD DEPRESSION - OPERATING CHARACTERISTICS OF THE MEDICAL OUTCOMES STUDY DEPRESSION SCREEN SO CLINICAL RESEARCH LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0009-9279 J9 CLIN RES JI Clin. Res. PD DEC PY 1992 VL 40 IS 4 BP A871 EP A871 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE141 UT WOS:A1992KE14100535 ER PT J AU SHANNON, DC AF SHANNON, DC TI PROSPECTIVE IDENTIFICATION OF THE RISK OF SIDS SO CLINICS IN PERINATOLOGY LA English DT Article ID INFANT-DEATH-SYNDROME; SLEEP-APNEA; SUDDEN; RESPONSES; POSITION; SIBLINGS; VICTIMS; HEALTH C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CHILDRENS SERV,PEDIAT PULM UNIT,BOSTON,MA 02114. HARVARD UNIV,MIT,SCH HLTH SCI & TECHNOL,BOSTON,MA 02115. NR 33 TC 5 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD DEC PY 1992 VL 19 IS 4 BP 861 EP 869 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA LA272 UT WOS:A1992LA27200011 PM 1464195 ER PT J AU DEMONACO, HJ AF DEMONACO, HJ TI THE EMPERORS NEW CLOTHES - REPLY SO CRITICAL CARE MEDICINE LA English DT Letter RP DEMONACO, HJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 1992 VL 20 IS 12 BP 1741 EP 1741 DI 10.1097/00003246-199212000-00032 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA KB929 UT WOS:A1992KB92900031 ER PT J AU HAIDER, N NEUMAN, R FOSTER, CS AHMED, AR AF HAIDER, N NEUMAN, R FOSTER, CS AHMED, AR TI REPORT ON THE SEQUENCE OF DQB1-ASTERISK-0301 GENE IN OCULAR CICATRICIAL PEMPHIGOID PATIENTS SO CURRENT EYE RESEARCH LA English DT Note ID MHC CLASS-II; SUSCEPTIBILITY; AUTOIMMUNITY; VULGARIS AB Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affects the conjunctiva and other mucous membranes. Major histocompatibility complex (MHC) class II genes are important in autoimmunity because the antigen is presented to the T cell receptor in association with these molecules. A highly statistically significant association has been observed between patients with OCP and DQw7 (DQB1*0301) gene. DNA sequences of the second and third exons of the DQB1*0301 gene were determined in three OCP patients and compared with a control homozygous cell line for DQw7 from the Tenth International Histocompatibility Workshop. The sequences were identical in the patients studied and reference cell line. This data indicates that DQB1*0301 may only partly provide the enhanced susceptibility to get OCP and that another gene(s) in linkage disequilibrium with it and other factors may play an important role in the pathogenesis. C1 CTR BLOOD RES,800 HUNTINGTON AVE,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,DEPT ORAL PATHOL,CAMBRIDGE,MA 02138. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114. FU NEI NIH HHS [EY08378]; NIDCR NIH HHS [DE09978] NR 19 TC 4 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD DEC PY 1992 VL 11 IS 12 BP 1233 EP 1238 DI 10.3109/02713689208999549 PG 6 WC Ophthalmology SC Ophthalmology GA KH955 UT WOS:A1992KH95500013 PM 1490342 ER PT J AU WALKER, WA AF WALKER, WA TI IMMUNOLOGY - EDITORIAL OVERVIEW SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article RP WALKER, WA (reprint author), MASSACHUSETTS GEN HOSP,MUCOSAL IMMUNOL LAB,149 13TH ST,BOSTON,MA 02129, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD DEC PY 1992 VL 8 IS 6 BP 963 EP 966 DI 10.1097/00001574-199212000-00012 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JW020 UT WOS:A1992JW02000012 ER PT J AU HASEGAWA, K WANDS, JR AF HASEGAWA, K WANDS, JR TI IMMUNOLOGY OF LIVER-DISEASES SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article AB The role of cellular immune responses in mediating hepatocyte injury of virus-infected cells is under active investigation. Induction of humor immunity to viral protein antigens may be important in hepatitis viral clearance from the host. Studies defining the critical epitopes on hepatitis B viral proteins that stimulate both B- and T-cell response are emerging. Interferon therapy is being used to treat individuals with chronic hepatitis B and C infection and may have effects on inhibiting viral replication and enhance HLA class I expression on hepatocytes as well as modulate B- and T-lymphocyte function. Detection of antibodies produced against hepatitis viral proteins and hepatocyte cellular antigens have become important in the diagnosis of acute and chronic active hepatitis. RP HASEGAWA, K (reprint author), MASSACHUSETTS GEN HOSP,MGH CANC CTR,MOLEC HEPATOL UNIT,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD DEC PY 1992 VL 8 IS 6 BP 1002 EP 1009 DI 10.1097/00001574-199212000-00018 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JW020 UT WOS:A1992JW02000018 ER PT J AU BUYNAK, RJ WINTER, HS AF BUYNAK, RJ WINTER, HS TI ACQUIRED-IMMUNODEFICIENCY-SYNDROME AND GASTROINTESTINAL IMMUNE FUNCTION SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article AB The gastrointestinal tract plays an important role in the nutritional and immunologic status of human immunodeficiency virus (HIV)-infected individuals. Defective mucosal immunoregulation contributes to the development of bacterial, viral, fungal, or protozoal opportunistic infections. Malabsorption also may occur without an identifiable enteric pathogen. HIV-infected children become lactose intolerant earlier than would be predicted by age or nationality. Although the mechanism is unknown, the mucosal immune system may regulate epithelial cell function through production of cytokines. The role of HIV in the production of cytokines and the relationship to malabsorption remains to be determined. The hypothesis that malabsorption and infection are exacerbated by malnutrition and potentiated by immunodeficiency may lead to the development of effective strategies for nutritional intervention. This has particular relevance for the HIV-infected child. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD DEC PY 1992 VL 8 IS 6 BP 1010 EP 1014 DI 10.1097/00001574-199212000-00019 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JW020 UT WOS:A1992JW02000019 ER PT J AU GRAYBILL, JR SHARKEYMATHIS, PK AF GRAYBILL, JR SHARKEYMATHIS, PK TI NEW ANTIFUNGAL AGENTS SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review AB Prior to 1980, systemic mycoses and their management received very little attention in either the medical literature or the priorities of pharmaceutical companies. Amphotericin B and flucytosine were sufficiently effective and toxic mycoses were sufficiently uncommon so that there was little motivation to search for alternatives. More recently, increased cytotoxic drug use and acquired immunodeficiency syndrome have been associated with dramatic increases of diseases such as disseminated candidiasis, cryptococcosis, aspergillosis, and histoplasmosis. This increase in turn has prompted a vigorous exploration of both old and new classes of antifungal drugs, and we are now living in exciting times for medical mycology. RP GRAYBILL, JR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,INFECT DIS SERV,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD DEC PY 1992 VL 5 IS 6 BP 773 EP 780 PG 8 WC Infectious Diseases SC Infectious Diseases GA KA228 UT WOS:A1992KA22800005 ER PT J AU DELARUBIA, G OLIVER, FJ INOGUCHI, T KING, GL AF DELARUBIA, G OLIVER, FJ INOGUCHI, T KING, GL TI INDUCTION OF RESISTANCE TO ENDOTHELIN-1S BIOCHEMICAL ACTIONS BY ELEVATED GLUCOSE-LEVELS IN RETINAL PERICYTES SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; VASCULAR SMOOTH-MUSCLE; MICROVASCULAR PERICYTES; INOSITOL TRISPHOSPHATE; DIABETIC-RETINOPATHY; CELLS; DIACYLGLYCEROL; STIMULATION; INSULIN; GROWTH AB Because retinal pericytes have contractile properties and are affected by diabetes, we have studied the responsiveness of pericytes to ET-1, a potent vasoconstrictor, in the presence of various concentrations of glucose. Cultured calf retinal pericytes were exposed to glucose levels of 5.5 or 25 mM for up to 8 days. Radioreceptor studies that used [I-125]ET-1 showed that pericytes contained high-affinity binding sites with K(d) of 3 x 10(-10) M, and these binding affinities were unaffected by glucose concentration. Receptor number appears to be elevated, but this increase was NS. Responsiveness of pericytes to ET-1 was studied with respect to stimulation of DAG and IP3 levels and PKC activities. In contrast to receptor binding, exposure to 25 mM glucose for >6 days blunted pericyte responsiveness to ET-1. The time course of ET-1 stimulation as measured by [H-3]glycerol labeling, and IP3 level showed a 98% increase in [H-3]DAG at 10 min and a fourfold increase for IP3, respectively. Cells exposed to 25 mM glucose only had a 32% increase for DAG, and no increase for IP3 was observed. Dose-response studies on the stimulation of [H-3]DAG increase showed the range of ET-1's effect to be between 10(-9) and 10(-7) M. At maximum, cells exposed to 5.5 mM glucose had a 70% increase versus only a 30% increase in those exposed to 25 mM glucose. Similarly, ET-1 only increased the total DAG levels in pericytes exposed to 5.5 mM glucose by 41%. PKC activity also was measured because DAG is one of its cellular activators. In cells exposed to 5 mM glucose, ET-1 increased PKC-specific activity in the membraneous pool after 30 min by two-to fourfold without changes in the cytosol. In those cells exposed to 25 mM glucose, no increase in the membranous PKC activity was noted. These findings show that exposure of pericytes to elevated levels of glucose can cause resistance to some of ET-1's biochemical actions at the postreceptor sites. Possibly, the loss of pericyte function as observed in early diabetic retinopathy could be attributable to the developed resistance to ET-1 in the retinal microvessels. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,SCH MED, DIV RES, BOSTON, MA 02215 USA. FU PHS HHS [NEI 05110, NEI 09178] NR 38 TC 56 Z9 56 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1992 VL 41 IS 12 BP 1533 EP 1539 DI 10.2337/diabetes.41.12.1533 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KA593 UT WOS:A1992KA59300005 PM 1446793 ER PT J AU GULLI, G FERRANNINI, E STERN, M HAFFNER, S DEFRONZO, RA AF GULLI, G FERRANNINI, E STERN, M HAFFNER, S DEFRONZO, RA TI THE METABOLIC PROFILE OF NIDDM IS FULLY ESTABLISHED IN GLUCOSE-TOLERANT OFFSPRING OF 2 MEXICAN-AMERICAN NIDDM PARENTS SO DIABETES LA English DT Review ID DEPENDENT DIABETES-MELLITUS; INVIVO INSULIN ACTION; MUSCLE GLYCOGEN-SYNTHESIS; PIMA-INDIANS; FATTY-ACID; BETA-CELL; INDIRECT CALORIMETRY; FOREARM GLUCOSE; NATURAL-HISTORY; HIGH PREVALENCE AB NIDDM patients with overt fasting hyperglycemia are characterized by multiple defects involving both insulin secretion and insulin action. At this point of the natural history of NIDDM, however, it is difficult to establish which defects are primary and which are acquired secondary to insulinopenia and chronic hyperglycemia. To address this question, we have studied the glucose-tolerant offspring (probands) of two Mexican-American NIDDM parents. Such individuals are at high risk for developing NIDDM later in life. The probands are characterized by hyperinsulinamia in the fasting state and in response to both oral and intravenous glucose. Insulin-mediated glucose disposal (insulin clamp technique), measured at two physiological levels of hyperinsulinemia (approximately 240 and 450 pM [approximately 40 and 75 muU/ml]), was reduced by 43 and 33%, respectively. During both the low- and high-dose insulin clamp steps, impaired nonoxidative glucose disposal, which primarily represents glycogen synthesis, was the major defect responsible for the insulin resistance. During the lower dose insulin clamp step only, a small decrease in glucose oxidation was observed. No defect in suppression of HGP by insulin was demonstrable. The ability of insulin to inhibit lipid oxidation (measured by indirect calorimetry) and plasma FFA concentration was impaired at both levels of hyperinsulinemia. These results indicate that the glucose-tolerant offspring of two NIDDM parents are characterized by hyperinsulinemia and manifest all of the metabolic abnormalities that characterize the fully established diabetic state, including insulin resistance, a major impairment in nonoxidative glucose disposal, a quantitatively less important defect in glucose oxidation, and a diminished insulin-mediated suppression of lipid oxidation and plasma FFA concentration. C1 UNIV TEXAS,HLTH SCI CTR,DIV DIABET,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DIV EPIDEMIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NCRR NIH HHS [MO1-RR-01346]; NIDDK NIH HHS [DK-24092] NR 101 TC 239 Z9 242 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1992 VL 41 IS 12 BP 1575 EP 1586 DI 10.2337/diabetes.41.12.1575 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KA593 UT WOS:A1992KA59300011 PM 1446799 ER PT J AU WIDOM, B SIMONSON, DC AF WIDOM, B SIMONSON, DC TI INTERMITTENT HYPOGLYCEMIA IMPAIRS GLUCOSE COUNTERREGULATION SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; INSULIN-INDUCED HYPOGLYCEMIA; GLYCEMIC THRESHOLDS; HUMANS; RADIOIMMUNOASSAY; RESPONSES; SYMPTOMS; THERAPY; PLASMA AB IDDM patients who maintain strict glycemic control have impaired counterregulatory hormone and symptomatic responses to, hypoglycemia. To test the hypothesis that intermittent exposure to hypoglycemia plays an etiological role in these defective responses, we produced 4 consecutive dally episodes of hypoglycemia in 10 healthy, nondiabetic volunteers by using the insulin clamp technique. Fasting (5.3 +/- 0.1 vs. 5.4 +/- 0.1 mM) and nadir (2.3 +/- 0.1 vs. 2.4 +/- 0.1 mM) glucose levels achieved during insulin infusion did not differ on study days 1 and 4. In contrast, the glucose levels required to stimulate an increase in EPI (2.8 vs. 3.1 mM), glucagon (2.8 vs. 3.2 mM), cortisol (2.4 vs. 2.9 mM), GH (2.6 vs. 3.0 mM), and autonomic hypoglycemic symptoms (2.2 vs. 2.5 mM) were all significantly lower on study day 4 versus study day 1 (P < 0.005-0.05). Basal levels of EPI and cortisol, but not glucagon, GH, or NE also were reduced on the final study day. We conclude that intermittent hypoglycemia can result in attenuation of the hormonal and symptomatic responses to insulin-induced hypoglycemia and may contribute to the defective counterregulatory responses in patients with well-controlled IDDM. C1 JOSLIN DIABET CTR, DEPT INTERNAL MED, 1 JOSLIN PL, BOSTON, MA 02215 USA. NEW ENGLAND DEACONESS HOSP, BOSTON, MA 02215 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, BOSTON, MA 02115 USA. FU NIDDK NIH HHS [5P30-DK-36386] NR 29 TC 123 Z9 123 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD DEC PY 1992 VL 41 IS 12 BP 1597 EP 1602 DI 10.2337/diabetes.41.12.1597 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KA593 UT WOS:A1992KA59300013 PM 1446801 ER PT J AU LAMPETER, ER KISHIMOTO, TK ROTHLEIN, R MAINOLFI, EA BERTRAMS, J KOLB, H MARTIN, S AF LAMPETER, ER KISHIMOTO, TK ROTHLEIN, R MAINOLFI, EA BERTRAMS, J KOLB, H MARTIN, S TI ELEVATED LEVELS OF CIRCULATING ADHESION MOLECULES IN IDDM PATIENTS AND IN SUBJECTS AT RISK FOR IDDM SO DIABETES LA English DT Note ID HOMING RECEPTOR AB Serum levels of recently discovered circulating forms of adhesion molecules, ICAM-1 and L-selectin, were found to be elevated in IDDM patients and in subjects at risk for developing IDDM compared with 100 normal, nondiabetic blood donors. Both adhesion molecules were determined by sandwich ELISA. Serum concentrations of either clCAM-1 or cL-selectin were >2SD of normal mean in 10 of 14 recent-onset IDDM patients (P < 0.05). Serum levels of clCAM-1 and cL-selectin did not correlate. In first-degree relatives, elevated adhesion molecule levels were observed in the 6 ICA+ individuals and in the ICA- individuals all (n = 14) with a genetic risk of IDDM (sharing HLA-DR3 and/or -DR4 with the diabetic relative) but not in the HLA-DR3- and/or -DR4- relatives (n = 13). We conclude that elevated clCAM-1 and cL-selectin levels occur independently of ICA status and probably reflect ongoing immune processes in recent-onset IDDM patients and first-degree relatives at risk for IDDM. C1 HEINRICH HEINE UNIV,DIABET RES INST,HENNEKAMP 65,W-4000 DUSSELDORF 1,GERMANY. ELISABETH HOSP,ESSEN,GERMANY. BOEHRINGER INGELHEIM PHARMACEUT,RIDGEFIELD,CT. CTR BLOOD RES,BOSTON,MA. NR 11 TC 111 Z9 111 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1992 VL 41 IS 12 BP 1668 EP 1671 DI 10.2337/diabetes.41.12.1668 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KA593 UT WOS:A1992KA59300023 PM 1280239 ER PT J AU BERNARDS, A HAASE, VH MURTHY, AE MENON, A HANNIGAN, GE GUSELLA, JF AF BERNARDS, A HAASE, VH MURTHY, AE MENON, A HANNIGAN, GE GUSELLA, JF TI COMPLETE HUMAN NF1 CDNA SEQUENCE - 2 ALTERNATIVELY SPLICED MESSENGER-RNAS AND ABSENCE OF EXPRESSION IN A NEUROBLASTOMA LINE SO DNA AND CELL BIOLOGY LA English DT Article ID NEUROFIBROMATOSIS TYPE-1 GENE; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; ADENYLATE-CYCLASE; RAS GENE; GAP; PRODUCT; GTPASE; YEAST; IDENTIFICATION; MUTATIONS AB Neurofibromatosis type 1 (NF1) is caused by mutations in a large gene on chromosome 17q11.2. Previously described partial cDNAs for this gene predicted a protein related to yeast IRA1/IRA2 and the mammalian RAS GTPase activator protein GAP. To initiate a detailed study of the role of this gene in NF1, we have characterized a set of overlapping cDNAs that represent its complete coding sequence. Our results show that two differentially expressed human NF1 mRNAs differ by a 63-bp insertion in the GAP-related domain. These mRNAs predict two 2,818- and 2,839-amino acid proteins with calculated molecular masses of approximately 317 and 319 kD. Extensive similarity to IRA proteins is evident in a 1,450-amino-acid central segment, roughly between amino acids 900 and 2,350. However, the remainder of the NF1 protein is not significantly similar to other proteins. Interestingly, the SK-N-SH human neuroblastoma line expresses no detectable NF1 mRNA, indicating that expression of NF1 is not essential for viability of this neural crest-derived tumor cell line. C1 MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RI Hannigan, Greg/A-5092-2009; Haase, Volker Hans/A-6758-2013 OI Haase, Volker Hans/0000-0002-7051-8994 FU NINDS NIH HHS [NS22224] NR 25 TC 30 Z9 32 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD DEC PY 1992 VL 11 IS 10 BP 727 EP 734 DI 10.1089/dna.1992.11.727 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA KC374 UT WOS:A1992KC37400002 PM 1457041 ER PT J AU HOLLENBAUGH, D GROSMAIRE, LS KULLAS, CD CHALUPNY, NJ BRAESCHANDERSEN, S NOELLE, RJ STAMENKOVIC, I LEDBETTER, JA ARUFFO, A AF HOLLENBAUGH, D GROSMAIRE, LS KULLAS, CD CHALUPNY, NJ BRAESCHANDERSEN, S NOELLE, RJ STAMENKOVIC, I LEDBETTER, JA ARUFFO, A TI THE HUMAN T-CELL ANTIGEN GP39, A MEMBER OF THE TNF GENE FAMILY, IS A LIGAND FOR THE CD40 RECEPTOR - EXPRESSION OF A SOLUBLE FORM OF GP39 WITH B-CELL COSTIMULATORY ACTIVITY SO EMBO JOURNAL LA English DT Article ID TUMOR NECROSIS FACTOR; MONOCLONAL-ANTIBODY; MOLECULAR-CLONING; ANTI-BP50 CDW40; LYMPHOCYTES-B; SURFACE; PROTEIN; INTERLEUKIN-4; ACTIVATION; BP50 AB Signals delivered to B cells via CD40 can synergize with those provided by other B cell surface receptors to induce B cell proliferation and antibody class switching as well as modulate cytokine production and cell adhesion. Recently, it has been shown that the ligand for CD40 is a cell surface protein of approximately 39 kDa expressed by activated T cells, gp39. Here we report on the isolation and characterization of a cDNA clone encoding human gp39, a type II membrane protein with homology to TNF, and the construction and characterization of a soluble recombinant form of gp39. COS cell transfectants expressing gp39 synergized with either anti-CD20 mAb or PMA to drive strong B cell proliferation and alone were able to drive B cells to proliferate weakly. In all cases the B cell proliferation induced by gp39-expressing COS cells was reduced to background levels by the addition of soluble CD40. Unlike gp39-expressing COS cells, recombinant soluble gp39 was not mitogenic alone and required co-stimulation to drive B cell proliferation. These results suggest that B cells require a second signal besides gp39-CD40 to drive proliferation and that soluble gp39 alone in a non-membrane bound form is able to provide co-stimulatory signals to B cells. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT MICROBIOL,HANOVER,NH 03756. RP HOLLENBAUGH, D (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121, USA. FU NIAID NIH HHS [AI26296]; NIGMS NIH HHS [GM43257] NR 45 TC 483 Z9 490 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 DEC PY 1992 VL 11 IS 12 BP 4313 EP 4321 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JY101 UT WOS:A1992JY10100007 PM 1385114 ER PT J AU KOLANUS, W ROMEO, C SEED, B AF KOLANUS, W ROMEO, C SEED, B TI LINEAGE-INDEPENDENT ACTIVATION OF IMMUNE-SYSTEM EFFECTOR FUNCTION BY MYELOID FC-RECEPTORS SO EMBO JOURNAL LA English DT Article DE CYTOLYSIS; FC-GAMMA-RII; FC-RECEPTOR; MACROPHAGES ID CELL ANTIGEN RECEPTOR; COATED PIT LOCALIZATION; NATURAL-KILLER-CELLS; RAT-MOUSE-HUMAN; GAMMA-R GENES; T-CELL; TRANSFECTED CELLS; CYTOPLASMIC DOMAIN; SURFACE EXPRESSION; TRIGGER MOLECULES AB An emerging theme in immunology finds receptors which initiate cellular effector programs forming multichain complexes in which the ligand recognition elements associate with one or more 'trigger molecules' whose aggregation initiates a signal transduction cascade. The sequence motifs constituting the active sites of these trigger molecules are found in the T cell and B cell antigen receptors, and some Fc receptors, and appear to be central to effector function activation. For example, of the many molecules that mimic or potentiate the action of the T cell antigen receptor (TCR), none have yet been found to initiate effector programs autonomously in cells lacking TCR. We have devised two strategies to study activation mediated by myeloid Fc receptors, which appear not to associate with trigger molecules: the use of primary human cytolytic T cells as surrogate effector cells for genetically delivered receptors, and the use of vaccinia virus vectors to introduce genetically modified receptors into primary human monocytes. Using these approaches, we have found that the cytoplasmic domains of two Fc receptors show comparable function to equivalent domains of the trigger molecule family, but are not homologous to members of that family. RP KOLANUS, W (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. FU NIAID NIH HHS [AI27849] NR 59 TC 46 Z9 46 U1 0 U2 0 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 DEC PY 1992 VL 11 IS 13 BP 4861 EP 4868 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KC837 UT WOS:A1992KC83700021 PM 1464313 ER PT J AU NAKAMURA, T LIN, LL KHARBANDA, S KNOPF, J KUFE, D AF NAKAMURA, T LIN, LL KHARBANDA, S KNOPF, J KUFE, D TI MACROPHAGE COLONY STIMULATING FACTOR ACTIVATES PHOSPHATIDYLCHOLINE HYDROLYSIS BY CYTOPLASMIC PHOSPHOLIPASE-A(2) SO EMBO JOURNAL LA English DT Article DE ARACHIDONATE; CPLA2 EXPRESSION; LYSOPHOSPHATIDYLCHOLINE; MONOCYTES; PROSTAGLANDINS ID FACTOR-I RECEPTOR; PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; MARROW-DERIVED MACROPHAGES; CA2+-SENSITIVE CYTOSOLIC PHOSPHOLIPASE-A2; GLOMERULAR MESANGIAL CELLS; ARACHIDONIC-ACID; DIACYLGLYCEROL GENERATION; PROLIFERATION SIGNALS; MURINE MACROPHAGES AB The macrophage colony stimulating factor (M-CSF) is required for the proliferation and differentiation of monocytes. Previous studies have demonstrated that M-CSF stimulation is associated with phosphatidylcholine (PC) hydrolysis and increased formation of both diacylglycerol (DAG) and phosphorylcholine. The present work extends those results by demonstrating that treatment of human monocytes with M-CSF is associated with increases in a cytoplasmic Ca2+-dependent activity which hydrolyzes 1-palmitoyl,2-arachidonoyl PC to arachidonic acid. The finding that this hydrolysis of PC is associated with increases in production of lysophosphatidylcholine indicates that M-CSF stimulates a cytoplasmic phospholipase A2 (cPLA2) activity. These results are supported by the demonstration that M-CSF induces cPLA2 gene expression. M-CSF-induced increases in cPLA2 mRNA levels were biphasic and corresponded with rapid (30-60 min) and delayed (24-72 h) increases in cPLA2 activity. The results demonstrate that this effect of M-CSF on cPLA2 expression is controlled at least in part by post-transcriptional stabilization of cPLA2 transcripts. The finding that M-CSF treatment is also associated with phosphorylation of the cPLA2 protein further suggests that expression of this enzyme is regulated at multiple levels. Finally, the stimulation of cPLA2 activity and arachidonate release is supported by increases in prostaglandin (PG) synthesis. In this regard, levels of both PGE2 and PGF2alpha were increased in response to M-CSF. Taken together, these results indicate that M-CSF stimulates PC hydrolysis in human monocytes by inducing cPLA2 activity and thereby formation of eicosanoids. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115. GENET INST,CAMBRIDGE,MA 02140. RP KUFE, D (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA34183] NR 50 TC 118 Z9 120 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 DEC PY 1992 VL 11 IS 13 BP 4917 EP 4922 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KC837 UT WOS:A1992KC83700027 PM 1334462 ER PT J AU XUE, D FINNEY, M RUVKUN, G CHALFIE, M AF XUE, D FINNEY, M RUVKUN, G CHALFIE, M TI REGULATION OF THE MEC-3-GENE BY THE C-ELEGANS HOMEOPROTEINS UNC-86 AND MEC-3 SO EMBO JOURNAL LA English DT Article DE CAENORHABDITIS-ELEGANS; DNASE-I FOOTPRINTING; MEC-3; PROMOTER; UNC-86 ID TOUCH RECEPTOR NEURONS; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTORS; RNA-POLYMERASE; CELL IDENTITY; GENE; HOMEODOMAIN; EXPRESSION; PROTEINS; DIFFERENTIATION AB The mec-3 gene encodes a homeodomain protein with LIM repeats that is required for the specification of touch cell fate in Caenorhabditis elegans. Previous experiments suggested that mec-3 expression requires the product of the unc-86 gene, a POU-type homeoprotein, and mec-3 itself. We have analyzed the control of mec-3 expression by identifying potential cis regulatory elements in the mec-3 gene (by conservation in a related nematode and by DNase I footprinting using unc-86 and mec-3 proteins) and testing their importance by transforming C.elegans with mec-3lacZ fusions in which these sites have been mutagenized in vitro. Both unc-86 and mec-3 proteins bind specifically to the promoter of the mec-3 gene, suggesting that both proteins may be directly involved in the regulation of the mec-3 gene. In addition, the footprint pattern with mec-3 protein is altered in the presence of unc-86 protein. In vivo transformation experiments reveal that some of the binding regions of the two proteins are needed for general positive control and maintenance of mec-3 expression while others have no detectable, unique function. Interestingly, the unc-86 gene appears to be required not only to initiate mec-3 expression but also to maintain it. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP XUE, D (reprint author), COLUMBIA UNIV,DEPT BIOL SCI,1012 FAIRCHILD,NEW YORK,NY 10027, USA. OI XUE, DING/0000-0002-8429-8136 FU NIGMS NIH HHS [GM30997] NR 35 TC 91 Z9 103 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 DEC PY 1992 VL 11 IS 13 BP 4969 EP 4979 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA KC837 UT WOS:A1992KC83700033 PM 1361171 ER PT J AU HARRINGER, W HODAKOWSKI, GT SVIZZERO, T JACOBS, EE VLAHAKES, GJ TREASURE, T AF HARRINGER, W HODAKOWSKI, GT SVIZZERO, T JACOBS, EE VLAHAKES, GJ TREASURE, T TI ACUTE EFFECTS OF MASSIVE TRANSFUSION OF A BOVINE HEMOGLOBIN BLOOD SUBSTITUTE IN A CANINE MODEL OF HEMORRHAGIC-SHOCK SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article; Proceedings Paper CT 5TH ANNUAL MEETING OF THE EUROPEAN ASSOC FOR CARDIO-THORACIC SURGERY CY SEP 23-24, 1991 CL LONDON, ENGLAND SP EUROPEAN ASSOC CARDIO THORAC SURG DE BLOOD SUBSTITUTES; HEMORRHAGIC SHOCK; HEMODYNAMICS; OXYGEN METABOLISM; DOGS AB The capability of stroma-free hemoglobin solutions to act as a plasma expander with oxygen and carbon dioxide transport properties has encouraged the idea of their possible use in settings of massive blood loss. Using a canine hemorrhagic shock model (systolic arterial pressure less-than-or-equal-to 50 torr for 60 min), we evaluated the efficacy of an ultra-pure stroma-free bovine hemoglobin solution (PBHg) as a resuscitation fluid in hypovolemic and acidotic animals, using homologous blood (PRBC) and 10% human serum albumin (HSA) as control solutions. Following volume replacement, dogs were studied for 2 h under anesthesia and for 4 h subsequently while awake. Resuscitation with PBHg (30 +/- 3 ml/kg) was able to restore stable hemodynamics and correct acidosis to an extent comparable to that in animals treated with PRBC. Additionally, oxygen transport was maintained at a higher level than that in dogs treated with HSA. Administration of PBHg in this shock model revealed no significant cardiopulmonary toxicity or adverse effects. These short-term results suggest that PBHg may be useful for effective resuscitation after major blood loss. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. NR 0 TC 40 Z9 40 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD DEC PY 1992 VL 6 IS 12 BP 649 EP 654 DI 10.1016/1010-7940(92)90189-5 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA KG999 UT WOS:A1992KG99900005 PM 1485975 ER PT J AU CAMPANERO, MR ARROYO, AG PULIDO, R URSA, A DEMATIAS, MS SANCHEZMATEOS, P KASSNER, PD CHAN, BMC HEMLER, ME CORBI, AL DELANDAZURI, MO SANCHEZMADRID, F AF CAMPANERO, MR ARROYO, AG PULIDO, R URSA, A DEMATIAS, MS SANCHEZMATEOS, P KASSNER, PD CHAN, BMC HEMLER, ME CORBI, AL DELANDAZURI, MO SANCHEZMADRID, F TI FUNCTIONAL-ROLE OF ALPHA-2/BETA-1 AND ALPHA-4/BETA-1 INTEGRINS IN LEUKOCYTE INTERCELLULAR-ADHESION INDUCED THROUGH THE COMMON BETA-1-SUBUNIT SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL-CELL-INTERACTIONS; MONOCLONAL-ANTIBODY; T-CELLS; FIBRONECTIN RECEPTOR; HOMOTYPIC ADHESION; CROSS-LINKING; ALPHA-CHAIN; VLA-4; ACTIVATION; SUBUNIT AB Whereas all of the integrins in the VLA protein subfamily are involved in cell-extracellular matrix interactions, only VLA-4 (through the alpha4 subunit) has been implicated in the triggering of intercellular adhesion. Here we describe that the VLA protein beta1 subunit (CD29) is also involved in the induction of homotypic cell aggregation. We have obtained three novel anti-beta1 monoclonal antibodies (mAb) with the ability to induce cell aggregation on different leukocyte cell types. These mAb recognize an antigenic site on the common beta1 chain of VLA proteins which is topographically and/or functionally distinct from other epitopes previously defined by several prototype anti-beta1 mAb. Induction of cell aggregation by anti-beta1 mAb is epitope specific, isotype and Fc independent, and displays kinetics similar to alpha4-mediated aggregation. This cell aggregation requires an intact cellular metabolism, the presence of divalent cations in the extracellular medium, and the integrity of the cytoskeleton. We also have found that the Na+/H+ antiporter may be essential for this process. For Ramos cells, which bear only the VLA alpha4/beta1 heterodimer, intercellular adhesion induced through the VLA-beta1 chain could be selectively inhibited by other anti-beta1 mAb as well as by anti-alpha4 mAb. Interestingly, anti-beta1 mAb which induced strong aggregation of VLA-alpha2- or VLA-alpha4-transfected K562 cells, had minimal effect on the alpha2- alpha4-alpha5+ K562 cell line. Furthermore, the beta1-mediated induction of cell aggregation on alpha2-K562- and alpha4-K562-transfected cells was blocked by preincubation with either anti-alpha2 or anti-alpha4 mAb, respectively, as well as by other anti-beta1 mAb. Interestingly, parental K562 cells were able to interact with both alpha2- and alpha4-transfected K562 cells, thus suggesting that counter-receptors for both integrins (VLA-2 and VLA-4) might exist on these cells. Together these results provide strong evidence supporting the involvement of alpha2/beta1 and alpha4/beta1 heterodimers in intercellular interactions and underline the pivotal role of the common beta1 chain of VLA proteins in the integrin-mediated induction of cell aggregation. C1 HOSP PRINCESA,SECC IMMUNOL,C DIEGO DE LEON 62,E-28006 MADRID,SPAIN. HOSP PRINCESA,UNIDAD BIOL MOLEC,E-28006 MADRID,SPAIN. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP SANCHEZMADRID, F (reprint author), HOSP PRINCESA,SECC IMMUNOL,C DIEGO DE LEON 62,E-28006 MADRID,SPAIN. RI Campanero, Miguel/A-4052-2013; Sanchez-Mateos, Paloma/E-8931-2013; Corbi, Angel/B-7194-2011; Garcia Arroyo, Alicia/L-2796-2014; Sanchez-Madrid, Francisco/M-7889-2016 OI Campanero, Miguel/0000-0003-1410-8621; Corbi, Angel/0000-0003-1980-5733; Garcia Arroyo, Alicia/0000-0002-1536-3846; Sanchez-Madrid, Francisco/0000-0001-5303-0762 FU NIGMS NIH HHS [GM 38903] NR 54 TC 69 Z9 69 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 1992 VL 22 IS 12 BP 3111 EP 3119 DI 10.1002/eji.1830221213 PG 9 WC Immunology SC Immunology GA KC886 UT WOS:A1992KC88600010 PM 1446704 ER PT J AU LIPTON, SA AF LIPTON, SA TI 7-CHLOROKYNURENATE AMELIORATES NEURONAL INJURY MEDIATED BY HIV ENVELOPE PROTEIN-GP120 IN RODENT RETINAL CULTURES SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Note DE GLYCINE ANTAGONIST SITE; AIDS; N-METHYL-D-ASPARTATE; GLUTAMATE NEUROTOXICITY; MAMMALIAN CENTRAL NEURONS; RETINAL GANGLION CELLS ID CALCIUM-CHANNEL ANTAGONISTS; AMINO-ACID NEUROTOXICITY; GANGLION-CELLS; NMDA RECEPTOR; GLUTAMATE NEUROTOXICITY; GLYCINE RECEPTOR; NERVOUS-SYSTEM; FRONTAL-CORTEX; COAT PROTEIN; RAT AB Prior studies with in vitro model systems have suggested that at least part of the neurological manifestations of AIDS may stem from neuronal injury involving the HIV-1 coat protein gp120. This form of neuronal damage is most probably mediated indirectly by a complex set of cellular interactions among macrophages, astrocytes, and neurons, resulting in a final common pathway of overstimulation of N-methyl-D-aspartate (NMDA) receptors. We studied the neuroprotective effect from gp120-induced neuronal injury of an antagonist of the glycine site of the NMDA receptor, 7-chlorokynurenate. In identified rat retinal ganglion cells in culture, we found that 50 muM 7-chlorokynurenate significantly abrogated the injury engendered by 20 pM gp120. Addition of 300 muM exogenous glycine prevented this protective effect of 50 muM 7-chlorokynurenate. These data suggest that glycine site antagonists of the NMDA receptor may have therapeutic potential for ameliorating neuronal damage associated with gp120. C1 CHILDRENS HOSP MED CTR,CELLULAR & MOLEC NEUROSCI LAB,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT NEUROL,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. NR 51 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC 1 PY 1992 VL 4 IS 12 BP 1411 EP 1415 DI 10.1111/j.1460-9568.1992.tb00167.x PG 5 WC Neurosciences SC Neurosciences & Neurology GA KH626 UT WOS:A1992KH62600023 ER PT J AU BEAL, MF AF BEAL, MF TI MECHANISMS OF EXCITOTOXICITY IN NEUROLOGIC DISEASES SO FASEB JOURNAL LA English DT Article DE GLUTAMATE; NEUROTOXICITY; AMYOTROPHIC LATERAL SCLEROSIS; PARKINSONS DISEASE; HUNTINGTONS DISEASE; ALZHEIMERS DISEASE; ISCHEMIA ID METABOTROPIC GLUTAMATE RECEPTOR; AMINO-ACID RECEPTORS; DEPENDENT PROTEIN-KINASE; CORTICAL CULTURES; NMDA RECEPTOR; NEURONAL DEGENERATION; HIPPOCAMPAL-NEURONS; MOLECULAR-CLONING; ION FLOW; NEUROTOXICITY AB Excitotoxicity refers to neuronal cell death caused by activation of excitatory amino acid receptors. A substantial body of-evidence has implicated excitotoxicity as a mechanism of cell death in both acute and chronic neurologic diseases. A major recent advance has been the successful cloning and expression of the N-methyl-D-aspartate (NMDA), non-NMDA, and metabotropic glutamate receptors. The cellular mechanisms responsible for cell death after activation of these receptors are still being clarified. In acute neurologic diseases such as stroke and head trauma, excitotoxicity may be related to excessive glutamate release. In chronic neurodegenerative diseases, however, a slow excitotoxic process is more likely to occur as a consequence of either a receptor abnormality or an impairment of energy metabolism. Recent therapeutic studies have demonstrated the efficacy of non-NMDA receptor antagonists in experimental studies of global ischemia. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BEAL, MF (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,FRUIT ST,BOSTON,MA 02114, USA. FU DS NIH HHS [NINDS 16367]; NINDS NIH HHS [NS 10828] NR 74 TC 320 Z9 336 U1 0 U2 5 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 DEC PY 1992 VL 6 IS 15 BP 3338 EP 3344 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA KD395 UT WOS:A1992KD39500004 PM 1464368 ER PT J AU REENAN, RAG KOLODNER, RD AF REENAN, RAG KOLODNER, RD TI ISOLATION AND CHARACTERIZATION OF 2 SACCHAROMYCES-CEREVISIAE GENES ENCODING HOMOLOGS OF THE BACTERIAL HEXA AND MUTS MISMATCH REPAIR PROTEINS SO GENETICS LA English DT Article ID BASE-PAIR MISMATCHES; HETERODUPLEX PLASMID DNA; CELL-FREE-EXTRACTS; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; NUCLEOTIDE-SEQUENCE; STREPTOCOCCUS-PNEUMONIAE; DROSOPHILA-MELANOGASTER; DIFFERENT EFFICIENCIES; MEIOTIC RECOMBINATION AB Homologs of the Escherichia coli (mutL, S and uvrD) and Streptococcus pneumoniae (hexA, B) genes involved in mismatch repair are known in several distantly related organisms. Degenerate oligonucleotide primers based on conserved regions of E. coli MutS protein and its homologs from Salmonella typhimurium, S. pneumoniae and human were used in the polymerase chain reaction (PCR) to amplify and clone mutS/hexA homologs from Saccharomyces cerevisiae. Two DNA sequences were amplified whose deduced amino acid sequences both shared a high degree of homology with MutS. These sequences were then used to clone the full-length genes from a yeast genomic library. Sequence analysis of the two MSH genes (MSH = mutS homolog), MSH1 and MSH2, revealed open reading frames of 2877 bp and 2898 bp. The deduced amino acid sequences predict polypeptides of 109.3 kD and 109.1 kD, respectively. The overall amino acid sequence identity with the E. coli MutS protein is 28.6% for MSH1 and 25.2% for MSH2. Features previously found to be shared by MutS homologs, such as the nucleotide binding site and the helix-turn-helix DNA binding motif as well as other highly conserved regions whose function remain unknown, were also found in the two yeast homologs. Evidence presented in this and a companion study suggest that MSH1 is involved in repair of mitochondrial DNA and that MSH2 is involved in nuclear DNA repair. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP REENAN, RAG (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115, USA. FU NHGRI NIH HHS [HG00305] NR 69 TC 198 Z9 201 U1 0 U2 11 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 1992 VL 132 IS 4 BP 963 EP 973 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA JZ832 UT WOS:A1992JZ83200010 PM 1459447 ER PT J AU REENAN, RAG KOLODNER, RD AF REENAN, RAG KOLODNER, RD TI CHARACTERIZATION OF INSERTION MUTATIONS IN THE SACCHAROMYCES-CEREVISIAE MSH1 AND MSH2 GENES - EVIDENCE FOR SEPARATE MITOCHONDRIAL AND NUCLEAR FUNCTIONS SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; MISMATCH REPAIR GENE; ESCHERICHIA-COLI; STREPTOCOCCUS-PNEUMONIAE; NUCLEOTIDE-SEQUENCE; SALMONELLA-TYPHIMURIUM; INITIATION SITE; MEIOTIC RECOMBINATION; DNA HELICASE; YEAST AB The MSH1 and MSH2 genes of Saccharomyces cerevisiae are predicted to encode proteins that are homologous to the Escherichia coli MutS and Streptococcus pneumoniae HexA proteins and their homologs. Disruption of the MSH1 gene caused a petite phenotype which was established rapidly. A functional MSH1 gene present on a single-copy centromere plasmid was incapable of rescuing the established msh1 petite phenotype. Analysis of msh1 strains demonstrated that mutagenesis and large-scale rearrangement of mitochondrial DNA had occurred. 4',6-Diamidino-2-phenylindole (DAPI) staining of msh1 yeast revealed an aberrant distribution of mtDNA. Haploid msh2 mutants displayed an increase of 85-fold in the rate of spontaneous mutation to canavanine resistance. Sporulation of homozygous msh2/msh2 diploids gave rise to a high level of lethality which was compounded during increased vegetative growth prior to sporulation. msh2 mutations also affected gene conversion of two HIS4 alleles. The his4x mutation, lying near the 5' end of the gene, was converted with equal frequency in both wild-type and msh2 strains. However, many of the events in the msh2 background were post-meiotic segregation (PMS) events (46.4 %) while none (<0.25 %) of the aberrant segregations in wild type were PMS events. The his4b allele, lying 1.6 kb downstream of his4x, was converted at a 10-fold higher frequency in the msh2 background than in the corresponding wild-type strain. Like the his4x allele, his4b showed a high level of PMS (30%) in the msh2 background compared to the corresponding wild-type strain where no (<0.26%) PMS events were observed. These results indicate that MSH1 plays a role in repair or stability of mtDNA and MSH2 plays a role in repair of 4-bp insertion/deletion mispairs in the nucleus. C1 HARVARD UNIV, SCH MED, DEPT BIOL CHEM & MOLEC PHARMACOL, BOSTON, MA 02115 USA. RP HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CELLULAR & MOLEC BIOL, BOSTON, MA 02115 USA. FU NHGRI NIH HHS [HG00305] NR 49 TC 289 Z9 296 U1 0 U2 19 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD DEC PY 1992 VL 132 IS 4 BP 975 EP 985 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA JZ832 UT WOS:A1992JZ83200011 PM 1334021 ER PT J AU SCOTT, HS NELSON, PV MACDONALD, ME GUSELLA, JF HOPWOOD, JJ MORRIS, CP AF SCOTT, HS NELSON, PV MACDONALD, ME GUSELLA, JF HOPWOOD, JJ MORRIS, CP TI AN 86-BP VNTR WITHIN IDUA IS THE BASIS OF THE D4S111 POLYMORPHIC LOCUS SO GENOMICS LA English DT Note ID ALPHA-L-IDURONIDASE; HUNTINGTON DISEASE; GENE C1 MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP SCOTT, HS (reprint author), ADELAIDE CHILDRENS HOSP INC,DEPT CHEM PATHOL,ADELAIDE,SA 5006,AUSTRALIA. RI Scott, Hamish/B-2122-2009; OI Scott, Hamish/0000-0002-5813-631X; Morris, Phillip/0000-0001-8976-619X FU NHGRI NIH HHS [HG00169]; NINDS NIH HHS [NS16367, NS22031] NR 7 TC 9 Z9 9 U1 2 U2 3 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 DEC PY 1992 VL 14 IS 4 BP 1118 EP 1120 DI 10.1016/S0888-7543(05)80145-4 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA KE785 UT WOS:A1992KE78500045 PM 1478658 ER PT J AU ALONSO, A AF ALONSO, A TI THE SHATTERED MIRROR - TREATMENT OF A GROUP OF NARCISSISTIC PATIENTS SO GROUP LA English DT Article AB Increasingly, group psychotherapy takes its place as a valid treatment model for patients with severe character pathology. This paper explores the impact of group treatment on a homogeneous group of patients with narcissistic character problems. The clinical example serves to illustrate the particular dynamics of this patient population; addresses the challenges inherent in treating these patients in a homogeneous, long-term therapy group; and, finally, underscores the countertransference pitfalls in such a clinical situation. Nonetheless, the successful working through of some of these patients' terrifying pathology supports the important of continuing experience and research into this arena. RP ALONSO, A (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WANG AMBULATORY CARE CTR,ACC-8,BOSTON,MA 02114, USA. NR 10 TC 3 Z9 3 U1 0 U2 0 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 WIN PY 1992 VL 16 IS 4 BP 210 EP 219 DI 10.1007/BF01458103 PG 10 WC Psychology, Clinical SC Psychology GA KC121 UT WOS:A1992KC12100002 ER PT J AU MACLAUGHLIN, DT LEVIN, RK CATLIN, EA TAYLOR, LA PREFFER, FI DONAHOE, PK AF MACLAUGHLIN, DT LEVIN, RK CATLIN, EA TAYLOR, LA PREFFER, FI DONAHOE, PK TI IDENTIFICATION OF MULLERIAN INHIBITING SUBSTANCE SPECIFIC BINDING IN HUMAN CELL-LINES SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE MULLERIAN INHIBITING SUBSTANCE; RECEPTOR; ANTIIDIOTYPIC ANTIBODY; BINDER ID GROWTH-FACTOR RECEPTOR; ANTI-IDIOTYPIC ANTIBODIES; INSULIN-RECEPTOR; CROSS-LINKING; MEMBRANES; PROTEIN; CROSSLINKING; REGRESSION; SYSTEM; DUCT AB The receptor for Mullerian Inhibiting Substance (MIS), a gonadal glycoprotein hormone, has not been previously identified. Plasma membranes from MIS-sensitive human tumor cell lines (HTB-111, endometrial carcinoma; and A-431, vulvar squamous carcinoma) were detergent extracted and incubated with I-125-labeled MIS anti-idiotypic antibody, or radioiodinated human recombinant MIS (I-125 rhMIS), with and without unlabeled competitors. I-125 anti-idiotypic MIS antibody bound to HTB- 111 membrane extracts was displaceable by unlabeled anti-idiotypic antibody, but not by anti-isotypic antibody prior to cross-linking. Specific binding of the anti-idiotypic MIS antibody to endometrial carcinoma cells was verified using fluorescence activated cell analysis and fluoresceinated antibody. Furthermore, unlabeled anti-idiotypic MIS antibody competed for I-125 rhMIS binding to A-431 vulvar carcinoma membranes. The labeled anti-idiotypic MIS antibody binding complex could be separated from P-32 labeled EGF receptor in the A-431 membranes, indicating that EGF, a natural inhibitor of MIS activity, and MIS itself bind to different receptors. These studies demonstrate a specific, displaceable binder for MIS in the plasmalemmae of two human tumor lines. Purification of this cell surface receptor protein will be greatly aided by using the MIS anti-idiotypic antibody. C1 MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DIV IMMUNOPATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,VINCENT RES LAB,BOSTON,MA 02114. FU NCI NIH HHS [CA 17393]; NHLBI NIH HHS [1R29 HL/HD46198-01]; NICHD NIH HHS [5F32 HD06645-02 CLN-3] NR 33 TC 7 Z9 9 U1 0 U2 1 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD DEC PY 1992 VL 24 IS 12 BP 570 EP 575 DI 10.1055/s-2007-1003392 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KD496 UT WOS:A1992KD49600006 PM 1478615 ER PT J AU REYNOLDS, JE FLETCHER, JA LYTLE, CH LI, N MORTON, CC DIEHL, SR AF REYNOLDS, JE FLETCHER, JA LYTLE, CH LI, N MORTON, CC DIEHL, SR TI MOLECULAR CHARACTERIZATION OF A 17Q11.2 TRANSLOCATION IN A MALIGNANT SCHWANNOMA CELL-LINE SO HUMAN GENETICS LA English DT Article ID NEUROFIBROMATOSIS TYPE-1 GENE; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; DNA POLYMORPHISMS; NF1 GENE; CHROMOSOME-17; MUTATIONS; TUMORS; GAP; BREAKPOINT; DELETIONS AB Malignant schwannomas are soft-tissue neoplasms that occur at increased frequency with germline alterations of the neurofibromatosis-1 (NF1) gene at 17q11.2. We report molecular and cytogenetic characterization of a malignant schwannoma cell line established from an individual affected with NF1. This cell line has a complex hyperdiploid karyotype with two cytogenetically identical der(13)t(13;17)(p11,q11.2) chromosomes. Using somatic cell hybrids, we mapped twelve chromosome-17 probes to either the der(13)t(13;17) chromosome or a small der(17) chromosome. Two chromosome-17p loci, including the p53 tumor suppressor gene, were present in the schwannoma cell line, but did not map to either of these chromosomes. Loss of heterozygosity studies indicated that the two der(13)t(13;17) chromosomes arose by duplication, presumably after the translocation event. The 17q11.2 translocation breakpoint maps distal to the NF1 gene, and may not disrupt its functioning. Although NF1 mRNA was detected in this cell line by polymerase chain reaction, Northern blot analysis revealed very little or none of the 13-kb mature NF1 transcript. This suggests that the single remaining allele of the NF1 gene contains a mutation that results in either greatly reduced transcription or message instability. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PSYCHIAT,POB 710,MCV STN,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DANA FARBER CANC INST,DEPT PEDIAT ONCOL,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP DIEHL, SR (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PSYCHIAT,POB 710,MCV STN,RICHMOND,VA 23298, USA. FU NCI NIH HHS [CA 16059, 1-K11-CA-01498-01] NR 45 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD DEC PY 1992 VL 90 IS 4 BP 450 EP 456 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA KC554 UT WOS:A1992KC55400023 PM 1483704 ER PT J AU LOUIS, DN VONDEIMLING, A DICKERSIN, GR DOOLING, EC SEIZINGER, BR AF LOUIS, DN VONDEIMLING, A DICKERSIN, GR DOOLING, EC SEIZINGER, BR TI DESMOPLASTIC CEREBRAL ASTROCYTOMAS OF INFANCY - A HISTOPATHOLOGIC, IMMUNOHISTOCHEMICAL, ULTRASTRUCTURAL, AND MOLECULAR GENETIC-STUDY SO HUMAN PATHOLOGY LA English DT Article DE BRAIN TUMORS; INFANT; ASTROCYTOMA; BASAL LAMINA; CHROMOSOME; LOSS OF HETEROZYGOSITY ID EXTRACELLULAR-MATRIX PROTEINS; GLIOMA CELL-LINE; FAVORABLE PROGNOSIS; GLIOFIBROMA; DIFFERENTIATION; TUMORIGENESIS; NEOPLASM; TUMORS; GROWTH; LIGHT C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,MOLEC NEUROONCOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. RP LOUIS, DN (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL NEUROPATHOL,WARREN 3,BOSTON,MA 02114, USA. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X FU NCI NIH HHS [F32 CA 09144] NR 25 TC 53 Z9 56 U1 0 U2 4 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 DEC PY 1992 VL 23 IS 12 BP 1402 EP 1409 DI 10.1016/0046-8177(92)90061-7 PG 8 WC Pathology SC Pathology GA KC912 UT WOS:A1992KC91200014 PM 1468778 ER PT J AU HASLOV, K FOMSGAARD, A TAKAYAMA, K FOMSGAARD, JS IBSEN, P FAUNTLEROY, MB STASHAK, PW TAYLOR, CE BAKER, PJ AF HASLOV, K FOMSGAARD, A TAKAYAMA, K FOMSGAARD, JS IBSEN, P FAUNTLEROY, MB STASHAK, PW TAYLOR, CE BAKER, PJ TI IMMUNOSUPPRESSIVE EFFECTS INDUCED BY THE POLYSACCHARIDE MOIETY OF SOME BACTERIAL LIPOPOLYSACCHARIDES SO IMMUNOBIOLOGY LA English DT Article ID III PNEUMOCOCCAL POLYSACCHARIDE; T-CELL ACTIVITY; MONOPHOSPHORYL LIPID-A; BORDETELLA-PERTUSSIS ENDOTOXIN; ANTIBODY-RESPONSE; CYSTIC-FIBROSIS; COMPARATIVE IMMUNOCHEMISTRY; POLYACRYLAMIDE GELS; B-CELLS; SUPPRESSOR AB The immunomodulatory properties of several lipopolysaccharides (LPS) derived from clinical isolates of Pseudomonas aeruginosa, Branhamella catarrhalis, and Bordetella pertussis were evaluated for their capacity to influence the magnitude of the antibody response to type III pneumococcal polysaccharide (SSS-III), which is known to be regulated by suppressor and amplifier T cells (Ts and Ta, respectively). The administration of LPS, two days after immunization resulted in a significant increase in the.antibody response. Such enhancement may be due mainly to the ability of the lipid A moiety of LPS to abolish the negative effects of activated Ts, thereby enabling Ta function to be more fully expressed; however, B cell mitogenicity of the LPS molecule also may be involved. By contrast, treatment with LPS at the time of immunization with SSS-III induces significant suppression of the SSS-III-specific antibody response; such suppression is not induced by LPS or lipid A derived from Escherichia coli and Salmonella minnesota, and is independent of the capacity of LPS to activate B cells polyclonally, an activity by attributed to the lipid A fraction of LPS. Studies conducted with the LPS of P. aeruginosa indicated that the suppression induced is T cell dependent and mediated by the polysaccharide (PS) fraction of LPS; it appears to be due - at least in part - to the capacity of PS to expand or increase the size of the precursor pool of Ts, activated in response to SSS-III. The significance of these findings to the pathogenesis of certain gram-negative infections is discussed. C1 NIAID,IMMUNOGENET LAB,TWINBROOK II RES FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852. STATENS SERUM INST,DEPT VACCINE,DK-2300 COPENHAGEN,DENMARK. RIGSHOSP,DEPT CLIN MICROBIOL,DK-2100 COPENHAGEN,DENMARK. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL LAB,MADISON,WI 53705. NR 58 TC 9 Z9 9 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD DEC PY 1992 VL 186 IS 5 BP 378 EP 393 PG 16 WC Immunology SC Immunology GA KE556 UT WOS:A1992KE55600004 PM 1286878 ER PT J AU NAKAO, S FUJII, A NIEDERMAN, R AF NAKAO, S FUJII, A NIEDERMAN, R TI ALTERATION OF CYTOPLASMIC CA-2+ IN RESTING AND STIMULATED HUMAN NEUTROPHILS BY SHORT-CHAIN CARBOXYLIC-ACIDS AT NEUTRAL PH SO INFECTION AND IMMUNITY LA English DT Note ID SUPEROXIDE ANION GENERATION; CALCIUM-MOBILIZING LIGANDS; ANAEROBIC-BACTERIA; INTRACELLULAR PH; FATTY-ACIDS; BY-PRODUCT; ACTIN POLYMERIZATION; CHEMOTACTIC PEPTIDE; SUCCINIC ACID; ACTIVATION AB The results reported here indicate that the short-chain carboxylic acids acetate and propionate stimulate cytoplasmic calcium mobilization in human polymorphonuclear leukocytes, while butyrate and lactate do not. Together with the results of previous work, this indicates that there are at least three classes of short-chain carboxylic acids: those which can alter only cytoplasmic pH (e.g., lactic acid), those which can alter cytoplasmic pH and actin (e.g., butyric acid), and those which can alter cytoplasmic pH, actin, and calcium (e.g., acetate and propionate). C1 FORSYTH RES INST,DEPT CELL BIOL,140 THE FENWAY,BOSTON,MA 02115. FU NIDCR NIH HHS [DE08415, DE04881] NR 30 TC 27 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1992 VL 60 IS 12 BP 5307 EP 5311 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JZ989 UT WOS:A1992JZ98900048 PM 1452365 ER PT J AU FOSTER, CS AF FOSTER, CS TI FUNGAL KERATITIS SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID ASPERGILLUS-FUMIGATUS; MICROBIAL KERATITIS; MICONAZOLE; KETOCONAZOLE; MANAGEMENT; KERATOMYCOSIS; THERAPY; RABBITS RP FOSTER, CS (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,243 CHARLES ST,BOSTON,MA 02115, USA. NR 17 TC 43 Z9 48 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1992 VL 6 IS 4 BP 851 EP 857 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KA183 UT WOS:A1992KA18300008 PM 1460266 ER PT J AU BELLIVEAU, JW KWONG, KK KENNEDY, DN BAKER, JR STERN, CE BENSON, R CHESLER, DA WEISSKOFF, RM COHEN, MS TOOTELL, RBH FOX, PT BRADY, TJ ROSEN, BR AF BELLIVEAU, JW KWONG, KK KENNEDY, DN BAKER, JR STERN, CE BENSON, R CHESLER, DA WEISSKOFF, RM COHEN, MS TOOTELL, RBH FOX, PT BRADY, TJ ROSEN, BR TI MAGNETIC-RESONANCE-IMAGING MAPPING OF BRAIN-FUNCTION - HUMAN VISUAL-CORTEX SO INVESTIGATIVE RADIOLOGY LA English DT Article DE BRAIN FUNCTION; CEREBRAL BLOOD FLOW; MAGNETIC RESONANCE IMAGING ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-VOLUME; COGNITIVE NEUROSCIENCE; HUMAN-EXPERIENCE; CONTRAST; SUSCEPTIBILITY; OXYGENATION; STIMULATION; DEPENDENCE; FIELDS AB Magnetic resonance imaging (MRI) studies of human brain activity are described. Task-induced changes in brain cognitive state were measured using high-speed MRI techniques sensitive to changes in cerebral blood volume (CBV), blood flow (CBF), and blood oxygenation. These techniques were used to generate the first functional MRI maps of human task activation, by using a visual stimulus paradigm. The methodology of MRI brain mapping and results from the investigation of the functional organization and frequency response of human primary visual cortex (V1) are presented. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RP BELLIVEAU, JW (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,NMR CTR,BLDG 149,13TH ST,BOSTON,MA 02129, USA. RI Kennedy, David/H-3627-2012; Fox, Peter/B-4725-2010; Cohen, Mark/C-6610-2011 OI Fox, Peter/0000-0002-0465-2028; Cohen, Mark/0000-0001-6731-4053 FU NHLBI NIH HHS [R01 HL039810, R01 HL039810-11] NR 43 TC 74 Z9 75 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD DEC PY 1992 VL 27 SU 2 BP S59 EP S65 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KC700 UT WOS:A1992KC70000011 PM 1468876 ER PT J AU ANG, RC HOOP, B KAZEMI, H AF ANG, RC HOOP, B KAZEMI, H TI BRAIN GLUTAMATE METABOLISM DURING METABOLIC ALKALOSIS AND ACIDOSIS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE BRAIN GLUTAMATE METABOLISM; ISOCAPNIC METABOLIC ALKALOSIS; ISOCAPNIC METABOLIC ACIDOSIS; NITROGEN-13-LABELED AMMONIA; NITROGEN-13-LABELED GLUTAMINE; CONTROL OF VENTILATION ID HYDROGEN-ION REGULATION; CEREBRAL BLOOD-FLOW; RAT-BRAIN; AMMONIA; HYPERCAPNIA; DOGS; CATS; CO2; PH AB Glutamate modifies ventilation by altering neural excitability centrally. Metabolic acid-base perturbations may also alter cerebral glutamate metabolism locally and thus affect ventilation. Therefore, the effect of metabolic acid-base perturbations on central nervous system glutamate metabolism was studied in pentobarbital-anesthetized dogs under normal acid-base conditions and during isocapnic metabolic alkalosis and acidosis. Cerebrospinal fluid transfer rates of radiotracer [N-13]ammonia and of [N-13]glutamine synthesized de novo via the reaction glutamate + NH3 --> glutamine in brain glia were measured during normal acid-base conditions and after 90 min of acute isocapnic metabolic alkalosis and acidosis. Cerebrospinal fluid [N-13]-ammonia and [N-13]glutamine transfer rates decreased in metabolic acidosis. Maximal glial glutamine efflux rate j(m) equals 85.6 +/- 9.5 (SE) mumol . l-1 . min-1 in all animals. No difference in j(m) was observed in metabolic alkalosis or acidosis. Mean cerebral cortical glutamate concentration was significantly lower in acidosis [7.01 +/- 0.45 (SE) mumol/g brain tissue] and tended to be larger in alkalosis, compared with 7.97 +/- 0.89 mumol/g in normal acid-base conditions. There was a similar change in cerebral cortical gamma-aminobutyric acid concentration. Within the limits of the present method and measurements, the results suggest that acute metabolic acidosis but not alkalosis reduces glial glutamine efflux, corresponding to changes in cerebral cortical glutamate metabolism. These results suggest that glutamatergic mechanisms may contribute to central respiratory control in metabolic acidosis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-29620, HL-29493] NR 24 TC 2 Z9 2 U1 1 U2 4 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 DEC PY 1992 VL 73 IS 6 BP 2552 EP 2558 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA KE844 UT WOS:A1992KE84400050 PM 1362726 ER PT J AU RADERMACHER, P FALKE, KJ PARK, YS AHN, DW HONG, SK QVIST, J ZAPOL, WM AF RADERMACHER, P FALKE, KJ PARK, YS AHN, DW HONG, SK QVIST, J ZAPOL, WM TI NITROGEN TENSIONS IN BRACHIAL VEIN BLOOD OF KOREAN AMA DIVERS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE BREATH-HOLD DIVING; EFFECTIVE DEPTH; VENOUS NITROGEN PARTIAL PRESSURE; DECOMPRESSION SICKNESS; COMPRESSION DECOMPRESSION PRINCIPLES ID DECOMPRESSION AB Intravascular bubble formation and symptoms of decompression sickness have been reported during repetitive deep breath-hold diving. Therefore we examined the pattern of blood N2 kinetics during and after repetitive breath-hold diving. To study muscle N2 uptake and release, we measured brachial venous N2 partial pressure (PN2) in nine professional Korean breath-hold divers (ama) during a 3-h diving shift at approximately 4 m seawater depth and up to 4 h after diving. PN2 was determined with the manometric Van Slyke method. Diving time and depth were recorded using a backpack computer-assisted dive logger that allowed calculating the surface-to-depth time ratio to derive the effective depth. With the assumption that forearm muscle N2 kinetics follow the general Haldanian principles of compression and decompression, i.e., forearm muscle is a single compartment with a uniform tissue PN2 equal to venous PN2, PN2 data were fitted to monoexponential functions of time. In the early phase of the diving shift, PN2 rapidly increased to 640 Torr (half time = 6 min) and then slowly declined to baseline levels (half time = 36 min) after the work shift. Peak PN2 levels approximated the alveolar PN2 derived from the effective depth. We conclude that forearm muscle N2 kinetics are well described by a Haldanian single-compartment model. Decompression sickness is theoretically possible in the ama; it did not occur because the absolute PN2 remained low due to the shallow working depth of the ama we studied. C1 FREE UNIV BERLIN,UNIV KLINIKUM RUDOLF VIRCHOW,INST ANAESTHESIOL & OPERAT INTENSIVMED,BERLIN,GERMANY. KOSIN MED COLL,INST DIVING SCI,DEPT PHYSIOL,PUSAN,SOUTH KOREA. SUNY BUFFALO,SCH MED & BIOMED SCI,DEPT PHYSIOL,BUFFALO,NY 14214. HERLEV HOSP,DEPT ANESTHESIA,DK-2730 HERLEV,DENMARK. MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP RADERMACHER, P (reprint author), HEINRICH HEINE UNIV,ZENTRUM ANAESTHESIOL,W-4000 DUSSELDORF,GERMANY. NR 19 TC 18 Z9 18 U1 0 U2 2 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 DEC PY 1992 VL 73 IS 6 BP 2592 EP 2595 PG 4 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA KE844 UT WOS:A1992KE84400056 PM 1490974 ER PT J AU MONTALESCOT, G HUERTA, JMM BRAQUET, P ZAPOL, WM AF MONTALESCOT, G HUERTA, JMM BRAQUET, P ZAPOL, WM TI ROLE OF PLATELET-ACTIVATING-FACTOR IN THE OVINE HEPARIN-PROTAMINE REACTION SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE PLATELET-ACTIVATING FACTOR RECEPTOR BLOCKADE; HYPOXIA; PROTAMINE REACTIONS ID PULMONARY VASCULAR-RESPONSE; AWAKE SHEEP; HYPERTENSION; VASOCONSTRICTION; COMPLEX; RELEASE AB Platelet-activating factor (PAF) infusion into sheep, as well as protamine reversal of heparin anticoagulation, causes thromboxane release into plasma, pulmonary hypertension, hypoxemia, and leukopenia. We investigated the possible role of PAF in the heparin-protamine reaction. Intravenous protamine was administered to neutralize heparin anticoagulation in five awake sheep and caused an increase of mean pulmonary arterial pressure from 16.6 +/- 1 (SE) mmHg at baseline to 47 +/- 9 mmHg at 1 min after protamine injection (P < 0.01) because of a 4.5-fold increase of pulmonary vascular resistance. This neutralization reaction induced a 25% reduction of circulating leukocyte count and arterial PO2. Undetectable blood levels of PAF were measured by bioassay and high-performance liquid chromatography during these heparin-protamine reactions. Infusion of BN 52021 (20 mg/kg), a PAF receptor antagonist, before rechallenging the same sheep with heparin and then protamine did not reduce the level of peak pulmonary hypertension or the degree of hypoxemia and leukopenia. We conclude that the leukopenia and thromboxane-mediated pulmonary vasoconstriction occurring after rapid intravascular formation of heparin-protamine complexes in sheep are not due to the release of PAF. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. INST H BEAUFOUR,F-92350 LE PLESSIS ROBINS,FRANCE. FU NHLBI NIH HHS [HL-42397] NR 15 TC 2 Z9 2 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 DEC PY 1992 VL 73 IS 6 BP 2604 EP 2607 PG 4 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA KE844 UT WOS:A1992KE84400058 PM 1490976 ER PT J AU MUEHRCKE, DD BLANK, S DAGGETT, WM AF MUEHRCKE, DD BLANK, S DAGGETT, WM TI SURVIVAL AFTER REPAIR OF POSTINFARCTION VENTRICULAR SEPTAL-DEFECTS IN PATIENTS OVER THE AGE OF 70 SO JOURNAL OF CARDIAC SURGERY LA English DT Article DE POSTMYOCARDIAL INFARCTION VENTRICULAR SEPTAL DEFECT IN THE ELDERLY AB Ventricular septal defect (VSD) is an infrequent but extremely serious complication of myocardial infarction. Operative mortality rates tend to be higher in the elderly population; however, long-term follow-up has not been specifically studied. It is, therefore, important to assess not only the early but also the long-term results of VSD repair in patients over 70 years of age to determine its value for the elderly patient. Between June 1968 and May 1991, 86 patients who experienced a myocardial infarction underwent surgical repair of an infarct related VSD at the Massachusetts General Hospital (MGH). Group I (n = 57) includes those patients younger than 70 years, and group II (n = 29) represents those patients age 70 years and older. Follow-up of hospital survivors ranged from 1 month to 24 years and was compiled in April and May, 1991. Three patients were lost to follow-up (4%), and these were younger than 70 years of age. There were no differences in the values of the preoperative variables for the younger and older groups with respect to sex, concomitant procedures performed (bypass vs no bypass), use of an intra-aortic balloon pump (IABP), location of VSD, presence of shock, total hospital days, or days between infarction and operation. There was, however, a difference between the two groups relative to the era when surgery was performed. More patients over the age of 70 underwent surgery after 1978 than before 1978 (p = 0.0012). The majority of survivors are in New York Heart Association (NYHA) Class I or II, and there was no difference between the younger and older groups in functional class at the time of follow-up (83.3% vs 91.7% of survivors in Class I or II, respectively). Using the generalized Wilcoxon test to analyze these survival data, there was no apparent difference in long-term survival (p = 0.97) when comparing the two age groups. The mean follow-up period was 77.02 months for the younger group and 80.52 months for the older group. The fact that more older patients were repaired after we had significant experience in the surgical management of patients with VSDs probably accounted for our excellent results in the older age group. Our data reveal that patients over the age of 70 can expect excellent long-term survival, with over 90% of these survivors remaining in NYHA Functional Class I or II. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,CARDIAC SURG UNIT,BOSTON,MA 02114. NR 0 TC 6 Z9 6 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD DEC PY 1992 VL 7 IS 4 BP 290 EP 300 DI 10.1111/j.1540-8191.1992.tb01019.x PG 11 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA KB866 UT WOS:A1992KB86600001 PM 1482822 ER PT J AU AKINS, CW AF AKINS, CW TI HYPOTHERMIC FIBRILLATORY ARREST FOR CORONARY-ARTERY BYPASS-GRAFTING SO JOURNAL OF CARDIAC SURGERY LA English DT Article DE MYOCARDIAL PRESERVATION; CORONARY ARTERY BYPASS GRAFTING; FIBRILLATORY ARREST AB Hypothermic fibrillatory arrest is a technique of myocardial preservation that has a long history of use in cardiac surgery. Numerous studies have documented its efficacy in various subgroups of patients with coronary artery disease. This report reviews the research support of the tenets of the technique and reports the results with its utilization in 2,801 consecutive patients having isolated myocardial revascularization. RP AKINS, CW (reprint author), MASSACHUSETTS GEN HOSP,DEPT CARDIAC SURG,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD DEC PY 1992 VL 7 IS 4 BP 342 EP 347 DI 10.1111/j.1540-8191.1992.tb01024.x PG 6 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA KB866 UT WOS:A1992KB86600006 PM 1482827 ER PT J AU STAUB, O VERREY, F KLEYMAN, TR BENOS, DJ ROSSIER, BC KRAEHENBUHL, JP AF STAUB, O VERREY, F KLEYMAN, TR BENOS, DJ ROSSIER, BC KRAEHENBUHL, JP TI PRIMARY STRUCTURE OF AN APICAL PROTEIN FROM XENOPUS-LAEVIS THAT PARTICIPATES IN AMILORIDE-SENSITIVE SODIUM-CHANNEL ACTIVITY SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NA+ CHANNEL; BINDING-PROTEIN; MESSENGER-RNA; FUNCTIONAL RECONSTITUTION; EXPRESSION CLONING; OOCYTES; CDNA; EPITHELIUM; MEMBRANE; PURIFICATION AB High resistance epithelia express on their apical side an amiloride-sensitive sodium channel that controls sodium reabsorption. A cDNA was found to encode a 1,420-amino acid long polypeptide with no signal sequence, a putative transmembrane segment, and three predicted amphipathic alpha helices. A corresponding 5.2-kb mRNA was detected in Xenopus laevis kidney, intestine, and oocytes, with weak expression in stomach and eyes. An antibody directed against a fusion protein containing a COOH-terminus segment of the protein and an antiidiotypic antibody known to recognize the amiloride binding site of the epithelial sodium channel (Kleyman, T. R., J.-P. Kraehenbuhl, and S. A. Ernst. 1991. J. Biol. Chem. 266:3907-3915) immunoprecipitated a similar protein complex from [S-35]methionine-labeled and from apically radioiodinated Xenopus laevis kidney-derived A6 cells. A single approximately 130-kD protein was recovered from samples reduced with DTT. The antibody also cross-reacted by ELISA with the putative amiloride-sensitive sodium channel isolated from A6 cells (Benos, D. J., G. Saccomani, and S. Sariban-Sohraby. 1987. J. Biol. Chem. 262:10613-10618). Although the protein is translated, cRNA injected into oocytes did not reconstitute amiloride-sensitive sodium transport, while antisense RNA or antisense oligodeoxynucleotides specific for two distinct sequences of the cloned cDNA inhibited amiloride-sensitive sodium current induced by injection of A6 cell mRNA. We propose that the cDNA encodes an apical plasma membrane protein that plays a role in the functional expression of the amiloride-sensitive epithelial sodium channel. It may represent a subunit of the Xenopus laevis sodium channel or a regulatory protein essential for sodium channel function. C1 VET AFFAIRS MED CTR, PHILADELPHIA, PA 19104 USA. UNIV LAUSANNE, INST PHARMACOL & TOXICOL, CH-1005 LAUSANNE, SWITZERLAND. UNIV PENN, DEPT MED, PHILADELPHIA, PA 19104 USA. UNIV PENN, DEPT PHYSIOL, PHILADELPHIA, PA 19104 USA. UNIV LAUSANNE, INST BIOCHEM, CH-1066 EPALINGES, SWITZERLAND. UNIV ALABAMA, DEPT PHYSIOL & BIOPHYS, BIRMINGHAM, AL 35294 USA. RP STAUB, O (reprint author), SWISS INST EXPTL CANC RES, CH-1066 EPALINGES, SWITZERLAND. NR 45 TC 50 Z9 51 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1992 VL 119 IS 6 BP 1497 EP 1506 DI 10.1083/jcb.119.6.1497 PG 10 WC Cell Biology SC Cell Biology GA KD077 UT WOS:A1992KD07700011 PM 1334959 ER PT J AU RIVKEES, SA Fuleihan, GE BROWN, EM CRAWFORD, JD AF RIVKEES, SA Fuleihan, GE BROWN, EM CRAWFORD, JD TI TERTIARY HYPERPARATHYROIDISM DURING HIGH PHOSPHATE THERAPY OF FAMILIAL HYPOPHOSPHATEMIC RICKETS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID X-LINKED HYPOPHOSPHATEMIA; D-RESISTANT RICKETS; PARATHYROID-HORMONE; VITAMIN-D; HYPERCALCEMIC HYPERPARATHYROIDISM; SECONDARY HYPERPARATHYROIDISM; CALCIUM; CALCITRIOL; SECRETION; RELEASE AB We report the development of severe tertiary hyperparathyroidism in three girls treated for familial hypophosphatemic rickets and characterize parathyroid function in vivo and in vitro. All patients had been previously treated with relatively large doses of inorganic phosphorus (125 mm/day) and ergocalciferol or calcitriol for several years and had radiographic evidence of long-standing hyperparathyroidism. Even in the presence of extremely elevated PTH levels, oral phosphate lowered serum calcium levels in vivo and further stimulated PTH secretion. Profound multiglandular parathyroid hyperplasia was found in each patient at surgery. Examination of the secretory characteristics of the excised parathyroid tissue revealed that either relatively high calcium concentrations were generally needed to suppress PTH secretion or PTH secretion was not suppressible. Caution is recommended when relatively large doses of phosphate are used to treat familial hypophosphatemic rickets. C1 MASSACHUSETTS GEN HOSP, PEDIAT ENDOCRINE UNIT, BOSTON, MA 02114 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, ENDOCRINE HYPERTENS UNIT, BOSTON, MA 02115 USA. FU NCRR NIH HHS [3-M01-RR-02635]; NICHD NIH HHS [HD-00924]; NIDDK NIH HHS [DK-41415] NR 24 TC 59 Z9 60 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1992 VL 75 IS 6 BP 1514 EP 1518 DI 10.1210/jc.75.6.1514 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KD201 UT WOS:A1992KD20100025 PM 1464657 ER PT J AU BOEPPLE, PA FRISCH, LS WIERMAN, ME HOFFMAN, WH CROWLEY, WF AF BOEPPLE, PA FRISCH, LS WIERMAN, ME HOFFMAN, WH CROWLEY, WF TI THE NATURAL-HISTORY OF AUTONOMOUS GONADAL-FUNCTION, ADRENARCHE, AND CENTRAL PUBERTY IN GONADOTROPIN-INDEPENDENT PRECOCIOUS PUBERTY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MCCUNE-ALBRIGHT SYNDROME; HORMONE-RELEASING HORMONE; CONSTITUTIONALLY DELAYED GROWTH; FAMILIAL TESTOTOXICOSIS; SKELETAL MATURATION; DEPENDENT PUBERTY; SEXUAL PRECOCITY; ALPHA-SUBUNIT; SECRETION; ANALOG AB Gonadotropin-independent precocity (GIP) is a syndrome marked by precocious pubertal development in the absence of pubertal levels of gonadotropins. To investigate the discrete patterns of central nervous system, gonadal, adrenal, and skeletal maturation in this syndrome, we conducted longitudinal studies spanning up to 10 yr in two such affected individuals. A cross-sectional analysis of adrenal androgen secretion was performed in nine additional patients to assess further the time course of adrenarche in GIP. Serial evaluations revealed progression of secondary sexual characteristics, statural growth, and skeletal maturation, all consistent with ongoing exposure to pubertal gonadal steroid levels. On the other hand, adrenarche (n = 11) and spontaneous and GnRH-stimulated gonadotropin secretion (n = 2) progressed in chronological age-appropriate manners despite long term pubertal levels of gonadal sex steroid secretion. After the development of central puberty, as documented by the appearance of pulsatile gonadotropin secretion, we sought to determine whether the potential for gonadal autonomy persisted. Despite complete pituitary desensitization induced by administration of a GnRH agonist, both patients studied demonstrated an ongoing capacity to secrete pubertal levels of gonadal steroids. Our study suggests that the timing of adrenarche and central puberty in these subjects with GIP was apparently unaltered by prolonged exposure to gonadal steroids. Subsequent to the development of central puberty, pulsatile gonadotropin secretion may override and, thus, mask the underlying defect(s) in adolescents and adults with histories of GIP. RP BOEPPLE, PA (reprint author), MASSACHUSETTS GEN HOSP, REPROD ENDOCRINE UNIT, BARTLETT HALL, EXTENS 5, FRUIT ST, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NICHD NIH HHS [HD-18169, P30 HD028138] NR 25 TC 24 Z9 24 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1992 VL 75 IS 6 BP 1550 EP 1555 DI 10.1210/jc.75.6.1550 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KD201 UT WOS:A1992KD20100033 PM 1464663 ER PT J AU CAREW, JA QUINN, SM STODDART, JH LYNCH, DC AF CAREW, JA QUINN, SM STODDART, JH LYNCH, DC TI O-LINKED CARBOHYDRATE OF RECOMBINANT VONWILLEBRAND-FACTOR INFLUENCES RISTOCETIN-INDUCED BINDING TO PLATELET GLYCOPROTEIN-1B SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CHINESE HAMSTER OVARY CELLS; GLYCOSYLATION; PROTEIN BINDING; PLATELET AGGLUTINATION; ENDOTHELIUM ID HUMAN-ENDOTHELIAL CELLS; 2 DISTINCT DOMAINS; FACTOR-VIII; ANTIGEN-II; VENOM COAGGLUTININ; FACTOR MULTIMERS; SUGAR CHAIN; IB; BOTROCETIN; DISEASE AB By transfecting the full-length CDNA for human von Willebrand factor (vWf) into a line of Chinese hamster ovary cells with a defect in carbohydrate metabolism, we have prepared recombinant vWf specifically lacking O-linked carbohydrates. We have compared this under-glycosylated protein to fully glycosylated recombinant vWf with respect to several structural and binding properties. vWf deficient in O-linked glycans was synthesized, assembled into multimers, and secreted in an apparently normal manner and was not prone to degradation in the extracellular milieu. It did not differ from fully glycosylated vWf in ability to bind to heparin or to collagen type I but did interact less well with glycoprotein 1b on formalin-fixed platelets. This decreased interaction was evidenced in both a lessened overall binding to platelets and in diminished capacity to promote platelet agglutination, in the presence of ristocetin. In contrast, no difference was seen in platelet binding in the presence of botrocetin. These data indicate a possible role for O-linked carbohydrates in the vWf-glycoprotein 1b interaction promoted by ristocetin and suggest that abnormalities in carbohydrate modification might contribute to the altered ristocetin-dependent reactivity between vWf and platelets described for some variant forms of von Willebrand disease. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP CAREW, JA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,NEOPLAST DIS MECHANISMS LAB,44 BINNEY ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL-08270]; PHS HHS [41222, 31311] NR 57 TC 40 Z9 41 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 DEC PY 1992 VL 90 IS 6 BP 2258 EP 2267 DI 10.1172/JCI116112 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE763 UT WOS:A1992KE76300013 PM 1469086 ER PT J AU SUNDAY, ME HUA, J TORDAY, JS REYES, B SHIPP, MA AF SUNDAY, ME HUA, J TORDAY, JS REYES, B SHIPP, MA TI CD10/NEUTRAL ENDOPEPTIDASE 24.11 IN DEVELOPING HUMAN FETAL LUNG - PATTERNS OF EXPRESSION AND MODULATION OF PEPTIDE-MEDIATED PROLIFERATION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE BOMBESIN; COMMON ACUTE LYMPHOBLASTIC LEUKEMIA ANTIGEN; METALLOENDOPEPTIDASE; RESPIRATORY EPITHELIUM; GROWTH REGULATION ID GASTRIN-RELEASING PEPTIDE; LEUKEMIA ANTIGEN CD10; NEUTRAL ENDOPEPTIDASE; SMALL-CELL; MONOCLONAL-ANTIBODIES; GENE-EXPRESSION; GROWTH-FACTOR; EC 3.4.24.11; SUBSTANCE-P; BOMBESIN AB The cell membrane-associated enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) functions in multiple organ systems to downregulate responses to peptide hormones. Recently, CD10/NEP was found to hydrolyze bombesin-like peptides (BLP), which are mitogens for normal bronchial epithelial cells and small cell lung carcinomas. Growth of BLP-responsive small cell lung carcinomas was potentiated by CD10/NEP inhibition, implicating CD10/NEP in regulation of BLP-mediated tumor growth. BLP are also likely to participate in normal lung development because high BLP levels are found in fetal lung, and bombesin induces proliferation and maturation of human fetal lung in organ cultures and murine fetal lung in utero. To explore potential roles for CD10/NEP in regulating peptide-mediated human fetal lung development, we have characterized temporal and cellular patterns of CD10/NEP expression and effects of CD10/NEP inhibition in organ cultures. Peak CD10/NEP transcript levels are identified at 11-13 wk gestation by Northern blots and localized to epithelial cells and mesenchyme of developing airways by in situ hybridization. CD10/NEP immunostaining is most intense in undifferentiated airway epithelium. In human fetal lung organ cultures, inhibition of CD10/NEP with either phosphoramidon or SCH32615 increases thymidine incorporation by 166-182% (P < 0.025). The specific BLP receptor antagonist, [Leu13-psi(CH2NH)Leu14]bombesin abolishes these effects on fetal lung growth, suggesting that CD10/NEP modulates BLP-mediated proliferation. CD10/NEP expression in the growing front of airway epithelium and the effects of CD10/NEP inhibitors in lung explants implicate the enzyme in the regulation of peptide-mediated fetal lung growth. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MARYLAND,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21201. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. RP SUNDAY, ME (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [R01-CA55095]; NHLBI NIH HHS [R01-HL-44984] NR 50 TC 76 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 DEC PY 1992 VL 90 IS 6 BP 2517 EP 2525 DI 10.1172/JCI116145 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA KE763 UT WOS:A1992KE76300046 PM 1469102 ER PT J AU GOTTLIEB, D AF GOTTLIEB, D TI THE UNIDIRECTIONALITY OF CEREBRAL POLYOPIA SO JOURNAL OF CLINICAL NEURO-OPHTHALMOLOGY LA English DT Article ID PALINOPSIA AB Polyopia, visual perseveration in space, has been associated with seizure activity, afterimage formation, and the presence of visual field defects. It can be interpreted both as a positive and a negative visual phenomenon. A patient with polyopia associated with the acute onset of hemianopsia is presented. The phenomenon has been investigated objectively with a simple procedure. The polyopia was highly correlated to movement of the eyes into the hemianoptic visual field and to increased contrast but not duration of the stimulus. This type of polyopia could be the result of incomplete visual processing due to poor visuospatial localization in a hemianopic field. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. SPAULDING REHABIL HOSP,BOSTON,MA 02114. NR 19 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0272-846X J9 J CLIN NEURO-OPHTHAL PD DEC PY 1992 VL 12 IS 4 BP 257 EP 262 PG 6 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA KB691 UT WOS:A1992KB69100009 PM 1287051 ER PT J AU WEEKS, J AF WEEKS, J TI QUALITY-OF-LIFE ASSESSMENT - PERFORMANCE STATUS UPSTAGED SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CANCER-PATIENTS; INDEX; LUNG RP WEEKS, J (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 16 TC 45 Z9 45 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1992 VL 10 IS 12 BP 1827 EP 1829 PG 3 WC Oncology SC Oncology GA KA722 UT WOS:A1992KA72200001 PM 1453195 ER PT J AU TORMEY, DC GRAY, R ABELOFF, MD ROSEMAN, DL GILCHRIST, KW BARYLAK, EJ STOTT, P FALKSON, G AF TORMEY, DC GRAY, R ABELOFF, MD ROSEMAN, DL GILCHRIST, KW BARYLAK, EJ STOTT, P FALKSON, G TI ADJUVANT THERAPY WITH A DOXORUBICIN REGIMEN AND LONG-TERM TAMOXIFEN IN PREMENOPAUSAL BREAST-CANCER PATIENTS - AN EASTERN COOPERATIVE ONCOLOGY GROUP TRIAL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID L-PHENYLALANINE MUSTARD; COMBINATION CHEMOTHERAPY; DRUG-THERAPY; L-PAM; ADRIAMYCIN; METHOTREXATE; CYCLOPHOSPHAMIDE; DIBROMODULCITOL; 5-FLUOROURACIL; VINBLASTINE C1 HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,BOSTON,MA 02115. JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV PRETORIA,PRETORIA,SOUTH AFRICA. RP TORMEY, DC (reprint author), UNIV WISCONSIN,CTR CLIN SCI K4632,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NCI NIH HHS [CA 13650, CA 21076, CA 23318] NR 45 TC 57 Z9 59 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 DEC PY 1992 VL 10 IS 12 BP 1848 EP 1856 PG 9 WC Oncology SC Oncology GA KA722 UT WOS:A1992KA72200005 PM 1453199 ER PT J AU SMITH, DJ JOSHIPURA, K KENT, R TAUBMAN, MA AF SMITH, DJ JOSHIPURA, K KENT, R TAUBMAN, MA TI EFFECT OF AGE ON IMMUNOGLOBULIN CONTENT AND VOLUME OF HUMAN LABIAL GLAND SALIVA SO JOURNAL OF DENTAL RESEARCH LA English DT Article ID IMMUNE-RESPONSE; FLOW-RATE; ANTIGEN; STREPTOCOCCI; ANTIBODY AB Stimulated lower labial (LLGF) and parotid salivary volumes and IgG, IgA, and IgM concentrations were measured in 264 subjects whose ages ranged from 17 to 76 years. A significant (p <0.001) age-related decline in LLGF output was observed for subjects over this age range. Sixty-three percent of the subjects in the 18-20-year-old group (n = 46) secreted at least 10 muL of labial saliva in a 7-10-minute period, while approximately 70% of the subjects in the two oldest groups (61-70 and 71-76 years old) secreted less than 1 muL of LLGF during this time period (n = 64). No significant gender-based differences occurred in the volumes of labial saliva secreted. Stimulated parotid salivary flow showed no age-related trend in these subjects. Lower labial gland salivary IgA concentrations in an older population (mean age +/- SD = 55.6 yr +/- 1.3) were significantly lower (p < 0.025) than IgA concentrations in a younger population (20.7 yr +/- 0.8), when IgA was expressed as mug/mL LLGF collected. Immunoglobulin A concentrations in parotid saliva and IgG and IgM concentrations in labial and parotid saliva were not significantly different when the two age populations were compared. These data suggest that the physiological and immunological potential of labial gland saliva may decrease with age. C1 FORSYTH DENT CTR,DEPT BIOSTAT,BOSTON,MA 02115. RP SMITH, DJ (reprint author), FORSYTH DENT CTR,DEPT IMMUNOL,140 THE FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-06153, DE-07009] NR 31 TC 30 Z9 31 U1 0 U2 1 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 DEC PY 1992 VL 71 IS 12 BP 1891 EP 1894 DI 10.1177/00220345920710120701 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA KC289 UT WOS:A1992KC28900007 PM 1452889 ER PT J AU BELKIN, GS AF BELKIN, GS TI STRANGERS AT THE BEDSIDE - A HISTORY OF HOW LAW AND BIOETHICS TRANSFORMED MEDICAL DECISION-MAKING - ROTHMAN,D SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Book Review RP BELKIN, GS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 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 WIN PY 1992 VL 17 IS 4 BP 959 EP 967 DI 10.1215/03616878-17-4-959 PG 9 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 KV190 UT WOS:A1992KV19000015 ER PT J AU DADAMIO, L CLAYTON, LK AWAD, KM REINHERZ, EL AF DADAMIO, L CLAYTON, LK AWAD, KM REINHERZ, EL TI NEGATIVE SELECTION OF THYMOCYTES - A NOVEL POLYMERASE CHAIN REACTION-BASED MOLECULAR ANALYSIS DETECTS REQUIREMENTS FOR MACROMOLECULAR-SYNTHESIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR TRANSGENIC MICE; MAJOR HISTOCOMPATIBILITY COMPLEX; CELL ANTIGEN RECEPTOR; T-CELL; POSITIVE SELECTION; CLONAL ELIMINATION; ENTEROTOXIN-B; GENE SEGMENTS; DEATH; APOPTOSIS AB Self-tolerance is mainly established through clonal deletion of autoreactive T cells during thymic differentiation. The mechanisms by which deletion is achieved are poorly understood. Here we use a specific polymerase chain reaction-based system to characterize DNA fragmentation and show that after in vivo treatment of neonatal mice with staphylococcus enterotoxin B, selective apoptosis of Vbeta8+ thymocytes occurs. This process precedes detectable deletion of Vbeta8+ cells as determined by phenotypic analysis. Moreover, in vivo administration of cycloheximide and, to a lesser extent, actinomycin D, inhibits apoptosis of staphylococcus enterotoxin B specific thymocytes. Thus, macromolecular synthesis is a requirement for negative selection. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP DADAMIO, L (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA49232] NR 37 TC 26 Z9 26 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1992 VL 149 IS 11 BP 3550 EP 3553 PG 4 WC Immunology SC Immunology GA JY875 UT WOS:A1992JY87500017 PM 1331238 ER PT J AU BORDEN, EC KIM, K RYAN, L BLUM, RH SHIRAKI, M TORMEY, DC COMIS, RL HAHN, RG PARKINSON, DR AF BORDEN, EC KIM, K RYAN, L BLUM, RH SHIRAKI, M TORMEY, DC COMIS, RL HAHN, RG PARKINSON, DR TI PHASE-II TRIALS OF INTERFERON-ALPHA AND INTERFERON-BETA IN ADVANCED SARCOMAS SO JOURNAL OF INTERFERON RESEARCH LA English DT Article ID COOPERATIVE-ONCOLOGY-GROUP; ACTINOMYCIN-D; CYCLOPHOSPHAMIDE; ADRIAMYCIN AB Interferons (IFNs)-alpha and -beta were administered to patients with metastatic sarcomas in two different Eastern Cooperative Oncology Group studies. In one study, patients received IFN-alpha2b, 20 million units/m2 i.v. 5 days/week x 4, then 10 million units s.c. t.i.w. In the second study, patients received IFN-beta(ser) 180 million units t.i.w. Of 87 patients evaluable for response, there were three responses in 64 patients (5%) treated with IFN-alpha-2b and no responses in 23 patients treated with IFN-beta(ser). Severe or life-threatening fatigue with decline in performance status complicated treatment of 37% of patients receiving IFN-alpha2b and 17% of patients receiving IFN-beta(ser). Further investigation of IFNs in sarcomas should depend on evidence from preclinical studies demonstrating synergistic effects of IFNs combined with a cytoreductive modality which has proven activity in these malignancies. C1 UNIV WISCONSIN,CTR CLIN CANC,MADISON,WI 53792. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NYU MED CTR,NEW YORK,NY 10016. TUFTS UNIV,BOSTON,MA 02115. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. NCI,BETHESDA,MD 20892. RP BORDEN, EC (reprint author), MED COLL WISCONSIN,CTR CANC,8701 WATERTOWN PLANK RD,MILWAUKEE,WI 53226, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA 21076, CA 16395, CA 23318] NR 11 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0197-8357 J9 J INTERFERON RES JI J. Interferon Res. PD DEC PY 1992 VL 12 IS 6 BP 455 EP 458 DI 10.1089/jir.1992.12.455 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KC716 UT WOS:A1992KC71600010 PM 1289413 ER PT J AU HENDERSON, GI HU, ZQ JOHNSON, RF PEREZ, AB YANG, YQ SCHENKER, S AF HENDERSON, GI HU, ZQ JOHNSON, RF PEREZ, AB YANG, YQ SCHENKER, S TI ACYCLOVIR TRANSPORT BY THE HUMAN PLACENTA SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID PREGNANCY; ANTIPYRINE; GLUCOSE; ETHANOL; HERPES AB Genital Herpes simplex infection is noted increasingly in women of childbearing age and in neonates. Concern about transmission of herpes to the newborn has led to cesarean delivery of many pregnant women with a history of genital herpes. Severe herpes hepatitis has also been noted in pregnancy. Acyclovir is the drug of choice for this infectious organism. Because there are no data on the mechanism(s) of transport of this drug by the human placenta, this study addressed this issue. We used normal term human placentas. For study of overall placental transport of acyclovir, we used the single, isolated perfused cotyledon technique. For assessment of initial acyclovir uptake, we used microvesicles prepared from the maternal-facing syncytiotrophoblast. Overall transfer of acyclovir at therapeutic concentrations from maternal to fetal compartment was at a rate of about 30% that of a freely diffusible marker, antipyrine. The overall transport was not saturable, was not inhibited by 50-fold adenine concentration, and did not proceed against a concentration gradient. There was no placental metabolism of the drug. Fetal-to-maternal transfer of acyclovir was at a similar rate. In maternal-facing microvesicles net uptake of acyclovir was not saturable, but was temperature dependent and was inhibited by high concentrations of adenine and ganciclovir, but not by nucleosides (adenosine, cytidine, cytosine). These data are most consistent with a carrier-dependent, nucleobase-type uptake of the drug, but passive overall net transfer of acyclovir, dependent on its solubility characteristics. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP HENDERSON, GI (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GASTROENTEROL & NUTR,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NICHD NIH HHS [R01 HD26707] NR 19 TC 33 Z9 33 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 DEC PY 1992 VL 120 IS 6 BP 885 EP 892 PG 8 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA KA909 UT WOS:A1992KA90900014 PM 1453110 ER PT J AU GWATHMEY, JK HAJJAR, RJ AF GWATHMEY, JK HAJJAR, RJ TI CALCIUM-ACTIVATED FORCE IN A TURKEY MODEL OF SPONTANEOUS DILATED CARDIOMYOPATHY - ADAPTIVE-CHANGES IN THIN MYOFILAMENT CA-2+ REGULATION WITH RESULTANT IMPLICATIONS ON CONTRACTILE PERFORMANCE SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE CARDIOMYOPATHY; TURKEY; CAMP; SKINNED FIBERS; CAFFEINE; PROTEIN KINASE-A ID HYPERTROPHIED FERRET HEARTS; SKELETAL-MUSCLE; SKINNED FIBERS; TROPONIN-T; SARCOPLASMIC-RETICULUM; CROSSBRIDGE KINETICS; MESSENGER-RNA; DPI 201-106; ADULT-RAT; MYOCARDIUM C1 MASSACHUSETTS GEN HOSP, MED SERV, BOSTON, MA 02114 USA. HARVARD UNIV, BETH ISRAEL HOSP,SCH MED,CHARLES A DANA RES INST, DEPT MED,DIV CARDIOVASC, BOSTON, MA 02215 USA. HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, DEPT CELLULAR & MOLEC PHYSIOL THORNDIKE LAB, BOSTON, MA 02215 USA. FU NHLBI NIH HHS [HL-36797, HL-39091] NR 47 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD DEC PY 1992 VL 24 IS 12 BP 1459 EP 1470 DI 10.1016/0022-2828(92)91086-K PG 12 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA KG879 UT WOS:A1992KG87900007 PM 1338113 ER PT J AU GIRMEN, AS BAENZIGER, J HOTAMISLIGIL, GS KONRADI, C SHALISH, C SULLIVAN, JL BREAKEFIELD, XO AF GIRMEN, AS BAENZIGER, J HOTAMISLIGIL, GS KONRADI, C SHALISH, C SULLIVAN, JL BREAKEFIELD, XO TI RELATIONSHIP BETWEEN PLATELET MONOAMINE OXIDASE-B ACTIVITY AND ALLELES AT THE MAOB LOCUS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE MONOAMINE OXIDASE-B; MONOAMINE OXIDASE-A; PLATELETS; HUMAN; GT-REPEAT ELEMENT ID HUMAN BRAIN-STEM; ENZYME-ACTIVITY; NORRIE DISEASE; X-CHROMOSOME; A GENE; PLASMA; LOCALIZATION; ALCOHOLISM; SYMPTOMS AB Genetic variations in monoamine oxidase (MAO)-B activity have been proposed to have a contributory role in several neurologic and psychiatric diseases. Variations in activity could affect rates of degradation of exogenous amines, including toxins, precursors of toxins (like 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), or false transmitters, and of endogenous amines, such as neurotransmitters. In this study a highly polymorphic (GT)n repeat element was used to mark alleles at the MAOB locus. The MAOB allele status and levels of platelet MAO-B activity were determined for 41 control males. No correlation was noted between specific alleles and levels of MAO-B activity in this sample set. This suggests that the structural gene for MAOB is not usually the primary determinant of activity levels in platelets. C1 MASSACHUSETTS GEN HOSP E,CTR NEUROSCI,BLDG 149,13TH ST,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. INDIANA UNIV,MED CTR,ALCOHOL RES CTR,DEPT PSYCHIAT,INDIANAPOLIS,IN 46204. INDIANA UNIV,MED CTR,ALCOHOL RES CTR,DEPT PATHOL,INDIANAPOLIS,IN 46204. FU NIAAA NIH HHS [AA08683, P50-AA08711]; NINDS NIH HHS [NS21921] NR 36 TC 27 Z9 27 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1992 VL 59 IS 6 BP 2063 EP 2066 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA JY566 UT WOS:A1992JY56600011 PM 1431894 ER PT J AU HANDELSMAN, L ARONSON, M MAURER, G WIENER, J JACOBSON, J BERNSTEIN, D NESS, R HERMAN, S LOSONCZY, M SONG, IS HOLLOWAY, K HORVATH, T DONNELLY, N HIRSCHOWITZ, J ROWAN, AJ AF HANDELSMAN, L ARONSON, M MAURER, G WIENER, J JACOBSON, J BERNSTEIN, D NESS, R HERMAN, S LOSONCZY, M SONG, IS HOLLOWAY, K HORVATH, T DONNELLY, N HIRSCHOWITZ, J ROWAN, AJ TI NEUROPSYCHOLOGICAL AND NEUROLOGICAL MANIFESTATIONS OF HIV-1 DEMENTIA IN DRUG-USERS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ASYMPTOMATIC INDIVIDUALS; POLYDRUG USERS; AIDS; COMPLEX; ABNORMALITIES; INFECTION; DEFICITS AB The cognitive and motor deficits associated with human immunodeficiency virus-1 (HIV-1) infection have been studied using neurological examination and neuropsychological tests. However, drug users with HIV-1 infection generally have been excluded from such studies. Forty-four well-characterized drug users stratified by Centers for Disease Control staging were administered a standardized neurological examination and a battery of neuropsychological tests under single-blind conditions designed to minimize the acute effects of psychoactive substances. The results of the blind neurological examination were consistent with the previously ascertained clinical staging of HIV-1 infection. The pattern of neuropsychological deficits across HIV-1 states was similar to those found in cohorts of homosexual men. C1 VET AFFAIRS MED CTR,NEUROL SERV,BRONX,NY 10468. VET AFFAIRS MED CTR,INFECT DIS SERV,BRONX,NY 10468. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. RP HANDELSMAN, L (reprint author), BRONX VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. NR 41 TC 22 Z9 22 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1992 VL 4 IS 1 BP 21 EP 28 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HC253 UT WOS:A1992HC25300004 PM 1627958 ER PT J AU HANSEN, TE WEIGEL, RM BROWN, WL HOFFMAN, WF CASEY, DE AF HANSEN, TE WEIGEL, RM BROWN, WL HOFFMAN, WF CASEY, DE TI A LONGITUDINAL-STUDY OF CORRELATIONS AMONG TARDIVE-DYSKINESIA, DRUG-INDUCED PARKINSONISM, AND PSYCHOSIS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID MULTIVARIATE STATISTICAL-METHODS; RABBIT SYNDROME; COEXISTENCE; THERAPY; CLASSIFICATION; PHARMACOLOGY; ASSOCIATION; PREVALENCE; SYMPTOMS; EFFICACY AB Tardive dyskinesia (TD) and drug-induced parkinsonism (DIP) have been hypothesized to reflect opposing states of dopamine (DA) function. In this longitudinal study, 57 psychotic inpatients were rated repeatedly for TD, DIP, and psychosis while receiving neuroleptic medication. Cross-sectional correlations among TD, DIP, and psychosis were weak or nonexistent. Factor and cluster analyses found that 13 patients (23%) were classified into groups characterized by the expected negative correlations. Thus, only partial support was found for the hypothesis that TD and DIP represent opposing states of DA function. RP HANSEN, TE (reprint author), OREGON HLTH SCI UNIV,PORTLAND VET AFFAIRS MED CTR,DEPT PSYCHIAT,PSYCHIAT SERV,116A-P,POB 1034,PORTLAND,OR 97207, USA. FU NIMH NIH HHS [MH36657] NR 46 TC 2 Z9 2 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1992 VL 4 IS 1 BP 29 EP 35 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA HC253 UT WOS:A1992HC25300005 PM 1352714 ER PT J AU MAJOCHA, RE RENO, JM FRIEDLAND, RP VANHAIGHT, C LYLE, LR MAROTTA, CA AF MAJOCHA, RE RENO, JM FRIEDLAND, RP VANHAIGHT, C LYLE, LR MAROTTA, CA TI DEVELOPMENT OF A MONOCLONAL-ANTIBODY SPECIFIC FOR BETA/A4 AMYLOID IN ALZHEIMERS-DISEASE BRAIN FOR APPLICATION TO INVIVO IMAGING OF AMYLOID ANGIOPATHY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID PLAQUE CORE PROTEIN; CONGOPHILIC ANGIOPATHY; PRECURSOR; DIAGNOSIS; THERAPY; CORTEX; TUMORS; CANCER AB We evaluated the efficacy of murine monoclonal antibodies (Mabs) targeted to beta/A4 amyloid for development of procedures for the in vivo identification of amyloid angiopathy (AA) in Alzheimer's disease (AD). Mabs to beta/A4 amyloid were prepared and screened for effectiveness in visualizing AA and senile plaques in postmortem AD brain sections. They were assessed again after enzymatic cleavage to produce Fab fragments and after labeling with Tc-99m using a diamide dimercaptide ligand system. Modified and radiolabeled Fab fragments retained activity and specificity towards amyloid-laden blood vessels and senile plaques. A highly specific murine Mab, 10H3, was identified and characterized that fulfills criteria necessary for the development of a diagnostic imaging agent. Expansion and adaptation of these strategies may provide the methods and materials for the noninvasive analysis of AA in living patients, and permit assessment of the contribution of AA to the clinical and pathological features of AD. C1 MASSACHUSETTS GEN HOSP,NEUROBIOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. NEORX CORP,SEATTLE,WA. MALLINCKRODT MED INC,ST LOUIS,MO. UNIV HOSP CLEVELAND,CTR ALZHEIMER,CLEVELAND,OH 44106. CASE WESTERN RESERVE UNIV,DEPT NEUROL,CLEVELAND,OH 44106. RI Friedland, Robert/A-2834-2010 OI Friedland, Robert/0000-0001-5721-1843 FU NIA NIH HHS [AG08012, P01 AG02126] NR 32 TC 42 Z9 43 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 DEC PY 1992 VL 33 IS 12 BP 2184 EP 2189 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KB965 UT WOS:A1992KB96500030 PM 1460513 ER PT J AU HOCH, DB AF HOCH, DB TI BRAIN-DEATH - A DIAGNOSTIC DILEMMA SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material RP HOCH, DB (reprint author), MASSACHUSETTS GEN HOSP,EPILEPSY SERV,BOSTON,MA 02114, USA. OI Hoch, Daniel/0000-0002-4294-024X NR 15 TC 3 Z9 3 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 DEC PY 1992 VL 33 IS 12 BP 2211 EP 2213 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KB965 UT WOS:A1992KB96500035 PM 1460518 ER PT J AU LORENTE, CA SONG, BZ DONOFF, RB AF LORENTE, CA SONG, BZ DONOFF, RB TI HEALING OF BONY DEFECTS IN THE IRRADIATED AND UNIRRADIATED RAT MANDIBLE SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID RADIATION-THERAPY; ORAL CAVITY; MANAGEMENT; SEQUELAE; GRAFTS C1 HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. RP LORENTE, CA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02215, USA. NR 27 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 1992 VL 50 IS 12 BP 1305 EP 1309 DI 10.1016/0278-2391(92)90232-O PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA KA273 UT WOS:A1992KA27300011 PM 1447611 ER PT J AU GOODSON, JM AF GOODSON, JM TI CONDUCT OF MULTICENTER TRIALS TO TEST AGENTS FOR TREATMENT OF PERIODONTITIS SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE CLINICAL TRIALS; PERIODONTITIS THERAPY ID TETRACYCLINE FIBER THERAPY AB THE CONDUCT OF MULTICENTER TRIALS to test agents for treatment of periodontitis is conceptually similar to that of single center trials, but the requirement that centers ultimately be combined into a single result places much more stringent requirements on uniformity and control. Multicenter trials should be considered only if numbers of subjects or the ability to generalize to other treatment settings becomes a driving theme. General guidelines for the conduct of studies of this sort are suggested and problems that occur are discussed. Despite formidable difficulties that may occur, multicenter studies provide a convincing demonstration of an agent's therapeutic efficacy for the treatment of periodontitis. RP GOODSON, JM (reprint author), FORSYTH DENT CTR,DEPT PHARMACOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04881] NR 7 TC 6 Z9 6 U1 0 U2 0 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD DEC PY 1992 VL 63 IS 12 SU S BP 1058 EP 1063 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA KD633 UT WOS:A1992KD63300004 PM 1479526 ER PT J AU SIEVER, LJ TRESTMAN, RL SILVERMAN, JM AF SIEVER, LJ TRESTMAN, RL SILVERMAN, JM TI VALIDATION OF PERSONALITY-DISORDER ASSESSMENT BY BIOLOGIC AND FAMILY STUDIES SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article; Proceedings Paper CT WORKSHOP ON REASSESSING PERSONALITY DISORDERS CONSTRUCTS CY MAR, 1991 CL NEW YORK, NY SP NIMH ID PLASMA HOMOVANILLIC-ACID; SCHIZOPHRENIC-PATIENTS; AMINE METABOLITES; EYE TRACKING; SCHIZOTYPAL; AGGRESSION; TRANSMISSION; SPECIFICITY; DEPRESSION; SEROTONIN C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. RP SIEVER, LJ (reprint author), BRONX VET ADM MED CTR,DEPT PSYCHIAT 116A,130 W KINGSBRIDGE RD,BRONX,NY 10468, USA. NR 56 TC 3 Z9 3 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD WIN PY 1992 VL 6 IS 4 BP 301 EP 312 PG 12 WC Psychiatry SC Psychiatry GA KG280 UT WOS:A1992KG28000003 ER PT J AU WICKERTS, CJ BERG, B FROSTELL, C SCHMIDT, J BLOMQVIST, H ROSBLAD, PG KIHLSTROM, I MESSMER, K HEDENSTIERNA, G AF WICKERTS, CJ BERG, B FROSTELL, C SCHMIDT, J BLOMQVIST, H ROSBLAD, PG KIHLSTROM, I MESSMER, K HEDENSTIERNA, G TI INFLUENCE OF HYPERTONIC-HYPERONCOTIC SOLUTION AND FUROSEMIDE ON CANINE HYDROSTATIC PULMONARY-EDEMA RESORPTION SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID EXTRAVASCULAR LUNG WATER; END-EXPIRATORY PRESSURE; SMALL-VOLUME RESUSCITATION; THORACIC-DUCT FISTULA; LYMPH-FLOW; FLUID RESUSCITATION; ANESTHETIZED DOGS; SODIUM-TRANSPORT; EDEMA FORMATION; PEEP AB 1. This study aimed at enhancing the clearance of experimental hydrostatic pulmonary oedema in dogs using hypertonic-hyperoncotic solution (HHS) and furosemide. 2. Anaesthetized dogs (n = 20) were mechanically ventilated with a positive end-expiratory pressure of 10 cm H2O (1.0 kPa). 3. Hydrostatic pulmonary oedema was induced by inflating a balloon inserted into the left atrium and simultaneously infusing isotonic saline rapidly. Oedema formation was terminated by deflating the balloon and reducing the infusion rate. 4. Four groups were studied: A, control; B, furosemide; C, HHS and D, HHS + furosemide. HHS, 6 ml kg-1, was given as a bolus injection and furosemide, 1 mg kg-1, intravenously as a bolus followed by an infusion of 0.5 mg kg-1 h-1. All dogs were studied for 4 h. 5. Serum osmolarity, plasma colloid oncotic pressure and diuresis in groups C and D (HHS groups) substantially increased; haemoglobin concentration decreased and pulmonary arterial wedge pressure remained constant. 6. Despite the combination of these factors favouring fluid flux from the extravascular to the intravascular compartment, extravascular lung water measured with the double indicator dilution technique decreased no faster in the HHS groups than in the two other groups (from over 26 to approximately 19 ml kg-1 in groups A, C and D and to 14.7 in group B (only furosemide)). 7. This was confirmed by postmortem gravimetric measurements of extravascular lung water; A, 11.0 +/- 5.7; B, 9.7 +/- 3.3; C, 10.5 +/- 3.1 and D, 10.6 +/- 1.8 g kg-1. 8. We speculate that mechanisms other than effective Starling gradients and enhanced diuresis might define a maximal rate of pulmonary oedema clearance. C1 ERSTA HOSP,DEPT SURG,STOCKHOLM,SWEDEN. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. KABI PHARM,UPPSALA,SWEDEN. UNIV MUNICH,INST SURG RES,W-8000 MUNICH 2,GERMANY. DANDERYD HOSP,DEPT ANAESTHESIA & INTENS CARE,S-18288 DANDERYD,SWEDEN. RP WICKERTS, CJ (reprint author), UNIV HOSP UPPSALA,INST CLIN PHYSIOL,UPPSALA,SWEDEN. NR 54 TC 8 Z9 8 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC PY 1992 VL 458 BP 425 EP 438 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA KB903 UT WOS:A1992KB90300024 PM 1302272 ER PT J AU SCOTT, CS LORE, C OWEN, RG AF SCOTT, CS LORE, C OWEN, RG TI INCREASING MEDICATION COMPLIANCE AND PEER SUPPORT AMONG PSYCHIATRICALLY DIAGNOSED STUDENTS SO JOURNAL OF SCHOOL HEALTH LA English DT Article ID THERAPEUTIC REGIMENS; ADOLESCENTS COMPLIANCE; ADHERENCE; AUTONOMY C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WANG AMBULATORY CARE CTR,DEPT PSYCHIAT,BOSTON,MA 02114. MONTANARI RESIDENTIAL TREATMENT CTR,SOCIAL SERV,HIALEAH,FL 33010. RP SCOTT, CS (reprint author), UNIV MIAMI,SCH MED,DEPT PSYCHIAT D29,POB 016960,MIAMI,FL 33101, USA. NR 17 TC 8 Z9 8 U1 0 U2 0 PU AMER SCHOOL HEALTH ASSOC PI KENT PA PO BOX 708, KENT, OH 44240 SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD DEC PY 1992 VL 62 IS 10 BP 478 EP 480 PG 3 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA KH692 UT WOS:A1992KH69200007 PM 1289660 ER PT J AU MULROW, CD TULEY, MR AGUILAR, C AF MULROW, CD TULEY, MR AGUILAR, C TI SUSTAINED BENEFITS OF HEARING-AIDS SO JOURNAL OF SPEECH AND HEARING RESEARCH LA English DT Article DE HEARING AIDS; ELDERLY; EFFICACY; HEARING LOSS ID DEPRESSION; VALIDATION; SCALE AB This study was designed to evaluate long-term benefits of hearing aids in elderly individuals with hearing loss. A primary care cohort of 192 elderly, hearing-impaired veterans (mean age 72 +/- 6, 97% White, 94% retired) were assessed at baseline and at 4, 8, and 12 months after hearing aid fitting. Drop-out rates at 4, 8, and 12 months were 5%, 13%, and 16%, respectively. Outcome assessments included several quality-of-life scales: Hearing Handicap Inventory in the Elderly (HHIE), Quantified Denver Scale of Communication Function (QDS), Geriatric Depression Scale (GDS), and the Short Portable Mental Status Questionnaire (SPMSQ). All quality-of-life areas improved significantly from baseline to 4-month post-hearing aid fittings (p < 0.05). Social and emotional (HHIE), communication (QDS), and depression (GDS) benefits were sustained at 8 and 12 months, whereas cognitive changes (SPMSQ) reverted to baseline at 12 months. We conclude that hearing aids provide sustained benefits for at least a year in these elderly individuals with hearing impairment. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RP MULROW, CD (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 26 TC 88 Z9 92 U1 0 U2 8 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE RD, ROCKVILLE, MD 20852-3279 SN 0022-4685 J9 J SPEECH HEAR RES JI J. Speech Hear. Res. PD DEC PY 1992 VL 35 IS 6 BP 1402 EP 1405 PG 4 WC Language & Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA KR873 UT WOS:A1992KR87300024 PM 1494282 ER PT J AU WAXMAN, DJ AF WAXMAN, DJ TI REGULATION OF LIVER-SPECIFIC STEROID METABOLIZING CYTOCHROME-P450 - CHOLESTEROL 7-ALPHA-HYDROXYLASE, BILE-ACID 6-BETA-HYDROXYLASE, AND GROWTH HORMONE-RESPONSIVE STEROID-HORMONE HYDROXYLASES SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 1ST INTERNATIONAL SYMP ON A MOLECULAR VIEW OF STEROID BIOSYNTHESIS AND METABOLISM CY OCT 14-17, 1991 CL JERUSALEM, ISRAEL SP ARES SERONO SYMP ID ADULT-RAT HEPATOCYTES; MESSENGER-RNA EXPRESSION; 7 ALPHA-HYDROXYLASE; THYROID-HORMONE; GENE-EXPRESSION; MOLECULAR-CLONING; HEPATIC CYTOCHROME-P-450; PITUITARY REGULATION; LITHOCHOLIC ACID; DRUG OXIDATIONS AB The hydroxylation of cholesterol, bile acids, and steroid hormones by liver cytochrome P450 (CYP) enzymes proceeds with a high degree of regiospecificity, and contributes to both biosynthetic and catabolic pathways of sterol metabolism. CYP 7-catalyzed cholesterol 7alpha-hydroxylation, a key control point of bile acid biosynthesis, is regulated at a pretranslational step, probably transcription initiation, by multiple factors, including liver bile acid and cholesterol levels, thyroid hormone status, and diurnal rhythm. Hydrophobic bile acids, such as lithocholic acid, are converted to less cholestatic derivatives by 6beta-hydroxylation carried out by CYP 3A P450s, which also catalyze steroid hormone 6beta-hydroxylation reactions. Complex, gender-dependent developmental patterns characterize the expression of steroid 5alpha-reductase and several rat liver steroid hydroxylase CYPs. Multiple pituitary-dependent factors regulate the expression of these enzymes; of greatest importance are the gonadal steroids and the sex-dependent secretory patterns of growth hormone (GH) that they impart. The continuous presence of GH in circulation, a characteristic of adult female rats, positively regulates expression of the female-specific steroid disulfate 15beta-hydroxylase CYP 2C12, while expression of the male-specific steroid 16alpha- and 2alpha-hydroxylase CYP 2C11 is stimulated by the intermittent pituitary secretion of GH that occurs in adult male rats. Intermittent GH can stimulate CYP 2C11 gene expression even when the hormone presents to the hepatocyte at a non-physiological pulse amplitude, duration, and frequency, provided that an interpulse interval of no GH (obligatory recovery period) is maintained for at least 2.5 h. GH regulates the expression of the CYP 2C11 and CYP 2C12 genes at the level of transcription initiation. This process is probably mediated by sex-dependent and GH-regulated protein-DNA interactions, such as those observed in the 5'-flank of the CYP 2Cl2 gene. Thyroid hormone is a second major regulator of liver steroid hydroxylase P450 activity. It regulates these enzymes directly, at a pretranslational step, and indirectly, through its stimulation of pituitary GH secretion and by its positive effects on the expression of the flavoenzyme NADPH-P450 reductase, which catalyzes electron transfer that is obligatory for all microsomal steroid hydroxylation reactions. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP WAXMAN, DJ (reprint author), HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [R01 DK033765] NR 127 TC 83 Z9 84 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD DEC PY 1992 VL 43 IS 8 BP 1055 EP 1072 DI 10.1016/0960-0760(92)90333-E PG 18 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA KJ728 UT WOS:A1992KJ72800030 PM 22217850 ER PT J AU CANNON, JD ZILE, MR CRAWFORD, FA CARABELLO, BA AF CANNON, JD ZILE, MR CRAWFORD, FA CARABELLO, BA TI AORTIC-VALVE RESISTANCE AS AN ADJUNCT TO THE GORLIN FORMULA IN ASSESSING THE SEVERITY OF AORTIC-STENOSIS IN SYMPTOMATIC PATIENTS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONGESTIVE HEART-FAILURE; REPLACEMENT; ADULTS; AREA AB Objectives. This study was conducted to determine the utility of aortic valve resistance in assessing the severity of aortic stenosis. Background. Assessment of the severity of aortic stenosis has traditionally employed hemodynamic data and the Gorlin formula to calculate the area of the aortic valve. Recently, flow dependence of the Gorlin formula has been identified and the accuracy of the formula challenged. Aortic valve resistance, the quotient of gradient and cardiac output, has been advanced as potentially useful in assessing the severity of valve stenosis. Methods. We studied 48 symptomatic patients with an initial diagnosis of severe aortic stenosis based on a calculated aortic valve area of less-than-or-equal-to 0.8 cm2 by the Gorlin formula. Forty of these patients (Group I) were confirmed to have severe aortic stenosis, whereas 8 (Group II) were subsequently proved not to have severe aortic stenosis. The 18 patients in Group I with a valve area of 0.6 to 0.8 cm2 (Group IA) were directly compared with Group II patients who had a similar valve area. Results. Aortic valve area was nearly identical in Group IA and Group II patients (0.69 +/- 0.05 and 0.71 +/- 0.06 cm2, respectively, p = NS). However, aortic valve resistance was much less in Group II patients (212 +/- 6 vs. 316 +/- 11 dynes.s.cm-5, p < 0.0001). In this small cohort, aortic valve resistance achieved nearly complete separation of patients in Groups IA and II. Conclusions. In some patients with relatively mild aortic stenosis, the calculated valve area may indicate that the stenosis is severe. The use of aortic valve resistance in conjunction with the Gorlin formula helps separate patients with truly severe aortic stenosis from those with milder disease. C1 MED UNIV S CAROLINA,DIV CARDIOL,GAZES CARDIAC RES INST,171 ASHLEY AVE,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. MED UNIV S CAROLINA,DIV CARDIOTHORAC SURG,CHARLESTON,SC 29425. NR 21 TC 89 Z9 90 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 DEC PY 1992 VL 20 IS 7 BP 1517 EP 1523 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KB859 UT WOS:A1992KB85900011 PM 1452925 ER PT J AU TANAKA, R SPINALE, FG CRAWFORD, FA ZILE, MR AF TANAKA, R SPINALE, FG CRAWFORD, FA ZILE, MR TI EFFECT OF CHRONIC SUPRAVENTRICULAR TACHYCARDIA ON LEFT-VENTRICULAR FUNCTION AND STRUCTURE IN NEWBORN PIGS SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CONGESTIVE HEART-FAILURE; CONGENITAL AORTIC-STENOSIS; INDUCED CARDIOMYOPATHY; DIASTOLIC FUNCTION; WALL STRESS; HEMODYNAMIC DETERMINANTS; DILATED CARDIOMYOPATHY; DEVELOPMENTAL-CHANGES; EJECTION PERFORMANCE; CARDIAC-HYPERTROPHY AB Objectives. The purpose of this study was to examine the effects of supraventricular pacing tachycardia on left ventricular function and myocardial structure in newborn, immature pigs and to determine whether immature pigs respond to supraventricular tachycardia differently from adults. Background. Previous studies have shown that supraventricular tachycardia causes dilated cardiomyopathy in adult animals; however, in humans, supraventricular tachycardia-induced congestive heart failure occurs most frequently in children and newborns. Because some clinical diseases may cause myocardial failure in adults but rarely do so in children, it was hypothesized that the effects of supraventricular tachycardia in newborns may be different from those in adults. Methods. In two groups of newborn swine (3 weeks of age), left ventricular volume, mass and function were assessed with simultaneous echocardiography and cardiac catheterization and myocardial structure was examined with light and electron microscopy. Six piglets underwent 3 weeks of left atrial pacing tachycardia (240 beats/min) and six littermates served as a control group. Both groups were followed up for 3 weeks. Results. At the end of the protocol, left ventricular dimensions increased in the piglets with supraventricular tachycardia compared with values in the control group, but there were no differences in left ventricular mass. Systolic function, assessed by fractional shortening, peak ejection rate and maximal rate of pressure development, was decreased in the group with supraventricular tachycardia. The fractional shortening-end-systolic stress relation in the piglets with supraventricular tachycardia decreased below normal values. Left ventricular diastolic function assessed by the relaxation time constant was prolonged, the peak filling rate was decreased and left ventricular stiffness was increased in the supraventricular tachycardia group. The morphologic data demonstrated that supraventricular tachycardia did not change total myocyte volume but did decrease total myofibrillar volume. Conclusions. Supraventricular tachycardia caused dilated cardiomyopathy in immature pigs. These changes in left ventricular function were associated with a decrease in cellular contractile proteins. Thus, the effects of supraventricular tachycardia on left ventricular function and structure in immature animals were comparable to previous findings in mature animals. C1 MED UNIV S CAROLINA,DEPT MED,DIV CARDIOL,171 ASHLEY AVE,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT SURG,DIV CARDIOTHORAC,CHARLESTON,SC 29425. VET AFFAIRS MED CTR,RALPH H JOHNSON DEPT,CHARLESTON,SC. GAZES CARDIAC RES INST,CHARLESTON,SC. FU NHLBI NIH HHS [R29-HL45024] NR 50 TC 20 Z9 21 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 DEC PY 1992 VL 20 IS 7 BP 1650 EP 1660 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KB859 UT WOS:A1992KB85900028 PM 1452940 ER PT J AU COLIN, W DONOFF, RB AF COLIN, W DONOFF, RB TI RESTORING SENSATION AFTER TRIGEMINAL NERVE INJURY - A REVIEW OF CURRENT MANAGEMENT SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID INFERIOR ALVEOLAR NERVE; PNEUMATIC TOURNIQUET; MAXILLOFACIAL REGION; LINGUAL NERVE; SURGERY; RECONSTRUCTION; DYSESTHESIA; SENSIBILITY; ANESTHESIA; RECOVERY AB After a year, even the most expert peripheral nerve repair carries a poor prognosis. Early referral and intervention offer the best management of trigeminal nerve injuries. C1 MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. RP COLIN, W (reprint author), HARVARD UNIV,SCH DENT MED,DEPT ORAL & MAXILLOFACIAL SURG,188 LONGWOOD AVE,CAMBRIDGE,MA 02138, USA. NR 49 TC 16 Z9 16 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD DEC PY 1992 VL 123 IS 12 BP 80 EP 85 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA KA950 UT WOS:A1992KA95000016 PM 1309192 ER PT J AU HERBERT, V AF HERBERT, V TI EVERYONE SHOULD BE TESTED FOR IRON DISORDERS SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Review ID DIETARY IRON; IDIOPATHIC HEMOCHROMATOSIS; DEFICIENCY ANEMIA; EXTRINSIC TAG; VITAMIN-C; ABSORPTION; BIOAVAILABILITY; SUPEROXIDE; DIAGNOSIS; OVERLOAD AB Routinely measuring iron status is necessary because about 6% of Americans have negative iron balance, about 10% have a gene for positive balance, and about 1% have iron overload. Deviations from normal iron status are as follows (a) Stage I and II negative iron balance, ie, iron depletion: In these stages iron stores are low and there is no dysfunction. In stage I negative iron balance, reduced iron absorption produces moderately depleted iron stores. Stage II negative iron balance is characterized by severely depleted iron stores. More than half of all cases of negative iron balance fall into these two stages. When persons in these stages are treated with iron they never develop dysfunction or disease. (b) Stage III and IV negative iron balance, ie, iron deficiency: Iron deficiency is characterized by inadequate body iron for normal function, producing dysfunction and disease. In stage III negative iron balance, dysfunction is not accompanied by anemia; anemia develops in stage IV negative iron balance. (c) Stage I and II positive iron balance: Stage I positive balance usually lasts for several years with no dysfunction. Supplements of iron and/or vitamin C promote progression on to dysfunction or disease. Iron removal prevents progression to disease. Iron overload develops in stage II positive iron balance after years of iron overload has caused progressive damage to tissues and organs. Again, iron removal stops disease progression. There are a variety of indicators of iron status. Serum ferritin is in equilibrium with body-iron stores. Barring inflammation, each 1 ng (0.0179 nmol) ferritin per mL of serum indicates approximately 10 mg (0.179 mmol) of body iron stores. Very early (stage I) positive iron balance may best be recognized by measuring saturation of iron-binding capacity Conversely, measurement of serum ferritin may best reveal early (stage I and II) negative iron balance, although recent work suggests that serum total iron-binding capacity may be as good. C1 BRONX VET AFFAIRS MED CTR,HEMATOL & NUTR LAB,BRONX,NY 10468. RP HERBERT, V (reprint author), CUNY MT SINAI SCH MED,COMM STRENGTHEN NUTR,NEW YORK,NY 10029, USA. NR 92 TC 41 Z9 41 U1 0 U2 5 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD DEC PY 1992 VL 92 IS 12 BP 1502 EP 1509 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA KB772 UT WOS:A1992KB77200012 PM 1308123 ER PT J AU ROYALL, DR MAHURIN, RK GRAY, KF AF ROYALL, DR MAHURIN, RK GRAY, KF TI BEDSIDE ASSESSMENT OF EXECUTIVE COGNITIVE IMPAIRMENT - THE EXECUTIVE INTERVIEW SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID FRONTAL LOBES; PARKINSONS-DISEASE; SENILE DEMENTIA; ALZHEIMERS TYPE; HUMAN AUTONOMY; BEHAVIOR; SCHIZOPHRENIA AB Objective: This study is a pilot validation of the Executive Interview (EXIT), a novel instrument designed to assess executive cognitive function (ECF) at the bedside. Design: Inter-rater reliability testing and validation using inter-group comparisons across levels of care and measures of cognition and behavior. Participants: Forty elderly subjects randomly selected across four levels of care. Setting: Settings ranged from independent living apartments to designated Alzheimer's Special Care units in a single 537-bed retirement community. Measurements: The EXIT: a 10-minute, 25-item interview scored from 0-50 (higher scores = greater executive dyscontrol) was administered by a physician. Subjects were also administered the Mini-Mental State Exam (MMSE) and traditional tests of "frontal" executive function by a neuropsychologist, and the Nursing Home Behavior Problem Scale (NHBPS) by Licensed Vocational Nurses. Results: Interrater reliability was high (r = .90). EXIT scores correlated well with other measures of ECF. The interview discriminated among residents at each level of care. In contrast, the MMSE did not discriminate apartment-dwelling from residential care residents, or residential care from nursing home residents. The EXIT was highly correlated with disruptive behaviors as measured by the NHBPS (r = .79). Conclusions: These preliminary findings suggest that the EXIT is a valid and reliable instrument for the assessment of executive impairment at the bedside. It correlates well with level of care and problem behavior. It discriminates residents at earlier stages of cognitive impairment than the MMSE. C1 GERIATR RES EDUC & CLIN CTR, SAN ANTONIO, TX USA. UNIV TEXAS, HLTH SCI CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. AUDIE L MURPHY MEM VET ADM MED CTR, SAN ANTONIO, TX 78284 USA. RP ROYALL, DR (reprint author), UNIV TEXAS, HLTH SCI CTR, DEPT PSYCHIAT, 7703 FLOYD CURL DR, SAN ANTONIO, TX 78284 USA. NR 40 TC 389 Z9 393 U1 3 U2 15 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 DEC PY 1992 VL 40 IS 12 BP 1221 EP 1226 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA KA809 UT WOS:A1992KA80900006 PM 1447438 ER PT J AU GERETY, MB WINOGRAD, CH AVERYT, E DENINO, LA AF GERETY, MB WINOGRAD, CH AVERYT, E DENINO, LA TI GERIATRIC-MEDICINE - HOW WE WILL FARE WITH THE MEDICARE FEE SCHEDULE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID RELATIVE VALUE SCALE; SERVICES; WORK C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV TEXAS,SCH PUBL HLTH,SAN ANTONIO,TX 78285. STANFORD UNIV,SCH MED,CTR GERIATR RES EDUC & CLIN,PALO ALTO,CA 94304. VET ADM MED CTR,PALO ALTO,CA 94304. RP GERETY, MB (reprint author), GERIATR RES EDUC & CLIN CTR,7400 METON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [U01AG09117-01] NR 24 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1992 VL 40 IS 12 BP 1272 EP 1280 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA KA809 UT WOS:A1992KA80900015 PM 1447447 ER PT J AU GRAY, RJ AF GRAY, RJ TI FLEXIBLE METHODS FOR ANALYZING SURVIVAL-DATA USING SPLINES, WITH APPLICATIONS TO BREAST-CANCER PROGNOSIS SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE BREAST CANCER; CENSORED DATA; PENALIZED LIKELIHOOD; PROPORTIONAL HAZARDS; SPLINES ID PROPORTIONAL HAZARDS MODEL; REGRESSION-MODELS; LIKELIHOOD AB In this article some flexible methods for modeling censored survival data using splines are applied to the problem of modeling the time to recurrence of breast cancer patients. The basic idea is to use fixed knot splines with a fairly modest number of knots to model aspects of the data, and then to use penalized partial likelihood to estimate the parameters of the model. Test statistics are proposed which are analogs of those used in traditional likelihood analysis, and approximations to the distributions of these statistics are suggested. In an analysis of a large data set taken from clinical trials conducted by the Eastern Cooperative Oncology Group, these methods are seen to give useful insight into how prognosis varies as a function of continuous covariates, and also into how covariate effects change with follow-up time. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP GRAY, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115, USA. NR 23 TC 270 Z9 272 U1 3 U2 12 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1992 VL 87 IS 420 BP 942 EP 951 DI 10.2307/2290630 PG 10 WC Statistics & Probability SC Mathematics GA KB896 UT WOS:A1992KB89600004 ER PT J AU DELAMONTE, SM WANDS, JR AF DELAMONTE, SM WANDS, JR TI NEURONAL THREAD PROTEIN OVER-EXPRESSION IN BRAINS WITH ALZHEIMERS-DISEASE LESIONS SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE NEURONAL THREAD PROTEIN; ALZHEIMERS DISEASE; DOWNS SYNDROME; PARKINSONS DISEASE DEMENTIA; CNS NEURODEGENERATION ID SECRETORY PROTEIN; TAU-PROTEINS; GENE; A68 AB Neuronal thread protein (NTP) is a recently characterized molecule that is over-expressed in brains with Alzheimer's disease (AD) lesions. The present study encompasses a detailed analysis of NTP expression in AD compared with other neurodegenerative diseases and aged controls. Using a specific monoclonal antibody, NTP immunoreactivity was evaluated in 309 paraffin-embedded sections from 8 different regions of the frontal, parietal, and temporal lobes of 73 brains with AD, AD + Down's syndrome (DN), AD + Parkinson's disease (PD), PD dementia (PDD), aged controls, and disease controls with Huntington's disease, multi-infarct dementia, or schizophrenia. In 250 adjacent blocks of snap-frozen unfixed tissue the concentration of NTP (ng/mg of protein) was measured using a 3-site forward sandwich monoclonal antibody based immunoradiometric assay (M-IRMA). Immunohistochemical studies demonstrated that brains with AD, AD + PD, and AD + DN contained significantly higher densities of NTP immunoreactive neurons and more frequent immunostaining of neuropil and white matter fibers compared with PDD and aged controls (both P < 0.001) which had few or no AD lesions. In addition, the overall mean concentrations of NTP in AD, AD + PD, and AD + DN were significantly higher than in PDD and aged controls (P < 0.005). Greater degrees of NTP immunoreactivity and higher concentrations of the protein in cerebral tissue were significantly correlated with AD diagnosis and abundant neurofibrillary tangles (P < 0.005). The findings suggest that NTP over-expression may serve as a marker for the type of neuronal degeneration that occurs in AD. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR ALZHEIMERS DIS RES,DIV NEUROPATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DIV MED SERV,BOSTON,MA 02114. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [R01-AA02666]; NINDS NIH HHS [R01-NS29793] NR 21 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC PY 1992 VL 113 IS 2 BP 152 EP 164 DI 10.1016/0022-510X(92)90243-E PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA KD455 UT WOS:A1992KD45500003 PM 1487753 ER PT J AU BEAL, MF MATSON, WR AF BEAL, MF MATSON, WR TI NEUROCHEMICAL ABNORMALITIES IN HUNTINGTONS-DISEASE - NEUROTOXIC MECHANISMS AND NEUROTRANSMITTER CHANGES - REPLY SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Letter ID 3-HYDROXYKYNURENINE RP BEAL, MF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114, USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC PY 1992 VL 113 IS 2 BP 232 EP 233 DI 10.1016/0022-510X(92)90252-G PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA KD455 UT WOS:A1992KD45500012 ER PT J AU DYSON, N GUIDA, P MUNGER, K HARLOW, E AF DYSON, N GUIDA, P MUNGER, K HARLOW, E TI HOMOLOGOUS SEQUENCES IN ADENOVIRUS E1A AND HUMAN PAPILLOMAVIRUS E7 PROTEINS MEDIATE INTERACTION WITH THE SAME SET OF CELLULAR PROTEINS SO JOURNAL OF VIROLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; E2F TRANSCRIPTION FACTOR; LARGE T-ANTIGENS; CYCLIN-A; POLYACRYLAMIDE GELS; SUSCEPTIBILITY GENE; STRUCTURAL PROTEINS; DNA-SYNTHESIS; C-MYC; BINDING AB Studies of adenovirus EIA oncoprotein mutants suggest that the association of EIA with the retinoblastoma protein (pRB) is necessary for EIA-mediated transformation. Mutational analysis of E1A indicates that two regions of pRB are required for EIA to form stable complexes with the retinoblastoma protein. In addition to pRB binding, these regions are necessary for EIA association with several other cellular proteins, including p130, p107, cyclin A, and p33cdk2. Here we show that short synthetic peptides containing the pRB-binding sequences of E1A are sufficient for interaction with p107, cyclin A, and p130. The E7 protein of human papillomavirus type 16 contains an element that binds to pRB and appears to be functionally homologous to the EIA sequences. Peptides containing this region of the E7 protein were able to interact with p107, cyclin A, and p130 in addition to pRB. These findings suggest that the common mechanism of transformation used by these viral oncogenes involves their association with a set of polypeptides. C1 NIH,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. RP DYSON, N (reprint author), MASSACHUSETTS GEN HOSP CANC CTR,BOSTON,MA 02129, USA. OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [CA13106, CA54696] NR 58 TC 296 Z9 298 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 DEC PY 1992 VL 66 IS 12 BP 6893 EP 6902 PG 10 WC Virology SC Virology GA JY710 UT WOS:A1992JY71000007 PM 1331501 ER PT J AU WYATT, R THALI, M TILLEY, S PINTER, A POSNER, M HO, D ROBINSON, J SODROSKI, J AF WYATT, R THALI, M TILLEY, S PINTER, A POSNER, M HO, D ROBINSON, J SODROSKI, J TI RELATIONSHIP OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GP120 3RD VARIABLE LOOP TO A COMPONENT OF THE CD4 BINDING-SITE IN THE 4TH CONSERVED REGION SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; SOLUBLE CD4; RECEPTOR-BINDING; HIV-1 GP120; FUSION DOMAIN; HTLV-III/LAV; T4 MOLECULE; INFECTION AB Neutralizing antibodies that recognize the human immunodeficiency virus gp120 exterior envelope glycoprotein and are directed against either the third variable (V3) loop or conserved, discontinuous epitopes overlapping the CD4 binding region have been described. Here we report several observations that suggest a structural relationship between the V3 loop and amino acids in the fourth conserved (C4) gp120 region that constitute part of the CD4 binding site and the conserved neutralization epitopes. Treatment of the gp120 glycoprotein with ionic detergents resulted in a V3 loop-dependent masking of both linear C4 epitopes and discontinuous neutralization epitopes overlapping the CD4 binding site. Increased recognition of the native gp120 glycoprotein by an anti-V3 loop monoclonal antibody, 9284, resulted from single amino acid changes either in the base of the V3 loop or in the gp120 C4 region. These amino acid changes also resulted in increased exposure of conserved epitopes overlapping the CD4 binding region. The replication-competent subset of these mutants exhibited increased sensitivity to neutralization by antibody 9284 and anti-CD4 binding site antibodies. The implied relationship of the V3 loop, which mediates post-receptor binding steps in virus entry, and components of the CD4 binding region may be important for the interaction of these functional gp120 domains and for the observed cooperativity of neutralizing antibodies directed against these regions. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NYU,SCH MED,PUBL HLTH RES INST,NEW YORK,NY 10016. NYU,SCH MED,AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. LOUISIANA STATE UNIV,MED CTR,DEPT PEDIAT,NEW ORLEANS,LA 70112. NR 76 TC 121 Z9 121 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 DEC PY 1992 VL 66 IS 12 BP 6997 EP 7004 PG 8 WC Virology SC Virology GA JY710 UT WOS:A1992JY71000019 PM 1279195 ER PT J AU NGUYEN, LH KNIPE, DM FINBERG, RW AF NGUYEN, LH KNIPE, DM FINBERG, RW TI REPLICATION-DEFECTIVE MUTANTS OF HERPES-SIMPLEX VIRUS (HSV) INDUCE CELLULAR-IMMUNITY AND PROTECT AGAINST LETHAL HSV INFECTION SO JOURNAL OF VIROLOGY LA English DT Article ID TYPE-1 GLYCOPROTEIN-D; DNA-BINDING PROTEIN; TOXIC LYMPHOCYTES-T; VACCINIA VIRUS; NONSTRUCTURAL PROTEINS; ANTIBODY-RESPONSE; DELETION MUTANTS; GENETIC-EVIDENCE; GENITAL HERPES; B-CELLS AB Live viruses and live virus vaccines induce cellular immunity more readily than do inactivated viruses or purified proteins, but the mechanism by which this process occurs is unknown. A trivial explanation would relate to the ability of live viruses to spread and infect more cells than can inactivated virus. We have used live but replication-defective mutants to investigate this question. Our studies indicate that the immune responses of mice to live virus differ greatly from the responses to inactivated virus even when the virus does not complete a replicative cycle. Further, these studies indicate that herpes simplex virus-specific T-cell responses can be generated by infection with replication-defective mutant viruses. These data indicate that the magnitude of the cellular immunity to herpes simplex virus may be proportional to the number or quantity of different viral gene products expressed by an immunizing virus. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 FU NCI NIH HHS [CA26345]; NIAID NIH HHS [AI20382, AI20530] NR 48 TC 68 Z9 69 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 DEC PY 1992 VL 66 IS 12 BP 7067 EP 7072 PG 6 WC Virology SC Virology GA JY710 UT WOS:A1992JY71000027 PM 1331509 ER PT J AU LABERLAIRD, K SMITH, A SWINDLE, MM COLWELL, J AF LABERLAIRD, K SMITH, A SWINDLE, MM COLWELL, J TI EFFECTS OF ISOFLURANE ANESTHESIA ON GLUCOSE-TOLERANCE AND INSULIN-SECRETION IN YUCATAN MINIPIGS SO LABORATORY ANIMAL SCIENCE LA English DT Article ID SWINE AB Isoflurane's effect on intravenous glucose tolerance and insulin secretion was studied in six Yucatan minipigs. Unanesthetized animals, with previously placed indwelling venous catheters, were tested while resting comfortably in slings. The same animals were then retested during isoflurane anesthesia. Serum glucose and insulin concentrations were measured at predetermined times in response to an intravenous bolus of dextrose. The glucose disappearance rate (k), baseline plasma insulin concentration, the area under the insulin response curve, and the insulinogenic index were significantly lower in the anesthetized animals than in controls. The results of this study indicate that anesthesia with isoflurane significantly alters the glucose/insulin response to an intravenous glucose tolerance test and, therefore, is unsuitable for studies when glucose tolerance is to be assessed. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29425. RP LABERLAIRD, K (reprint author), MED UNIV S CAROLINA,DEPT COMPARAT MED,CHARLESTON,SC 29425, USA. NR 17 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD DEC PY 1992 VL 42 IS 6 BP 579 EP 581 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA KE139 UT WOS:A1992KE13900009 PM 1479810 ER PT J AU PALMIERI, SL PAYNE, J STILES, CD BIGGERS, JD MERCOLA, M AF PALMIERI, SL PAYNE, J STILES, CD BIGGERS, JD MERCOLA, M TI EXPRESSION OF MOUSE PDGF-A AND PDGF ALPHA-RECEPTOR GENES DURING PREIMPLANTATION AND POSTIMPLANTATION DEVELOPMENT - EVIDENCE FOR A DEVELOPMENTAL SHIFT FROM AN AUTOCRINE TO A PARACRINE MODE OF ACTION SO MECHANISMS OF DEVELOPMENT LA English DT Article DE PLATELET-DERIVED GROWTH FACTOR; TYROSINE KINASE RECEPTOR; MOUSE EMBRYOGENESIS ID GROWTH-FACTOR RECEPTOR; SIMIAN SARCOMA-VIRUS; SIGNAL TRANSDUCTION; HUMAN-FIBROBLASTS; KINASE-ACTIVITY; B CHAINS; EMBRYOGENESIS; CELLS; HOMODIMERS; PROTEINS AB We examined the expression of platelet-derived growth factor (PDGF)-A and the PDGF alpha-receptor in pre-implantation and early post-implantation mouse embryos. At two-cell and blastocyst stages, all cells express mRNA and protein for both ligand and receptor. In contrast, early post-implantation embryos express PDGF-A chain mRNA in both embryonic ectoderm and in the ectoderm lining the ectoplacental cavity, while mRNA for PDGF alpha-receptor is localized to the mesoderm layers of both embryonic and extra-embryonic membranes. At days 3.5 and 7.5, receptors are demonstrably functional in response to exogenous PDGF-AA. We propose that chronic autostimulation of PDGF alpha-receptors occurs in pre-implantation embryos, whereas, following implantation, early mesoderm development is dependent on stimulation by ectodermally produced PDGF-A. C1 HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,25 SHATTUCK ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HUMAN REPROD & REPROD BIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NICHD NIH HHS [HD21988, HD2496] NR 45 TC 56 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 1992 VL 39 IS 3 BP 181 EP 191 DI 10.1016/0925-4773(92)90045-L PG 11 WC Developmental Biology SC Developmental Biology GA KG001 UT WOS:A1992KG00100006 PM 1292572 ER PT J AU MANGIONE, CM PHILLIPS, RS SEDDON, JM LAWRENCE, MG COOK, EF DAILEY, R GOLDMAN, L AF MANGIONE, CM PHILLIPS, RS SEDDON, JM LAWRENCE, MG COOK, EF DAILEY, R GOLDMAN, L TI DEVELOPMENT OF THE ACTIVITIES OF DAILY VISION SCALE - A MEASURE OF VISUAL FUNCTIONAL STATUS SO MEDICAL CARE LA English DT Article DE ACTIVITIES OF DAILY VISION SCALE ID LENS IMPLANTATION; CATARACT; PREVALENCE; MANAGEMENT; DISEASE AB To develop a method for the evaluation of visual function in subjects with cataracts, the authors identified 20 visual activities and categorized them into five subscales (distance vision, near vision, glare disability, night driving, and daytime driving) that comprised the Activities of Daily Vision Scale (ADVS). Each subscale in the ADVS was scored between 100 (no visual difficulty) and 0 (inability to perform the activity because of visual difficulty). In 334 subjects scheduled for cataract extraction (mean age 75 +/- 9 years, 67% women), ADVS scores (mean +/- standard deviation) for each subscale ranged from 44 +/- 31 for night driving to 72 +/- 24 for near vision activities. When administered by telephone, inter-rater reliability coefficients (r) were 0.82 to 0.97 W < 0.001) for each of the subscales, and test-retest reliability was 0.87 for the scale overall. Cronbach's coefficient a was very high for both the in-person (alpha = -0.94) and telephone (alpha = 0.91) formats. Criterion validity, the correlation between visual loss and ADVS score, was 0.37 (P < 0.001) when the ADVS was administered in person and -0.39 (P < 0.001) when it was administered by telephone. Content validity as assessed with factor analysis showed that 88% of the variance of the principal components weighted on one factor. The authors conclude that substantial visual disability is not captured by routine visual testing and that the ADVS is a reliable and valid measure of patient's perception of visual functional impairment. C1 BETH ISRAEL HOSP,DEPT MED,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,DIV GEN MED,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT MAT SCI,HLTH UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT MAT SCI,GEN EYE SERV,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP MANGIONE, CM (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,DIV CLIN EPIDEMIOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU AHRQ HHS [FS32 HS00048-01] NR 17 TC 346 Z9 362 U1 2 U2 21 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 1992 VL 30 IS 12 BP 1111 EP 1126 DI 10.1097/00005650-199212000-00004 PG 16 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA KB776 UT WOS:A1992KB77600004 PM 1453816 ER PT J AU WISE, PH LOWE, JA AF WISE, PH LOWE, JA TI NOISE OR FUGUE - SEEKING THE LOGIC OF CHILD HEALTH INDICATORS SO MENTAL RETARDATION LA English DT Article AB Despite improvements in many child health indicators, several important ones, including the racial disparity in infant mortality, have not improved in recent years. A focus on dramatic but rare risk factors has distracted attention away from the primary determinants of these indicators. An analytic model to assess these indicators identifies three interacting determinates: (a) social well-being, (b) our technical capacity to reduce die risk that low social status conveys, and (c) our performance in providing access to this technical capacity. These three determinants can move independently and can, therefore, mask important trends in social status and the impact of programs and policies. C1 HARVARD UNIV,INST REPROD & CHILD HLTH,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. RP WISE, PH (reprint author), HARVARD UNIV,SCH MED,DEPT PEDIAT,RICHARDSON FULLER BLDG,SUITE 517,221 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC MENTAL RETARDATION PI WASHINGTON PA 444 N CAPITOL ST, NW, STE 846, WASHINGTON, DC 20001-1512 SN 0047-6765 J9 MENT RETARD JI Ment. Retard. PD DEC PY 1992 VL 30 IS 6 BP 323 EP 329 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA KD843 UT WOS:A1992KD84300005 PM 1474908 ER PT J AU FRETER, RR IRMINGER, JC PORTER, JA JONES, SD STILES, CD AF FRETER, RR IRMINGER, JC PORTER, JA JONES, SD STILES, CD TI A NOVEL 7-NUCLEOTIDE MOTIF LOCATED IN 3' UNTRANSLATED SEQUENCES OF THE IMMEDIATE-EARLY GENE SET MEDIATES PLATELET-DERIVED GROWTH-FACTOR INDUCTION OF THE JE GENE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SERUM RESPONSE ELEMENT; C-FOS GENE; BETA-INTERFERON GENE; MESSENGER-RNA DEGRADATION; 3T3 CELLS; TRANSCRIPTION FACTORS; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; SECRETORY PROTEIN; BINDING PROTEIN AB A cohort of the serum and growth factor regulated immediate-early gene set is induced with slower kinetics than c-fos. Two of the first immediate-early genes characterized as such, c-myc and JE, are contained within this subset. cis-acting genomic elements mediating induction of the slower responding subset of immediate-early genes have never been characterized. Herein we characterize two widely separated genomic elements which are together essential for induction of the murine JE gene by platelet-derived growth factor, serum, interleukin-1, and double-stranded RNA. One of these elements is novel in several regards. It is a 7-mer, TTTTGTA, found in the proximal 3' sequences downstream of the JE stop codon. The 3' element is position dependent and orientation independent. It does not function in polyadenylation, splicing, or destabilization of the JE transcript. Copies of the 7-mer or its inverse are found at comparable 3' sites in 25 immediate-early genes that encode transcription factors or cytokines. Given its general occurrence, the 7-mer may be a required cis-acting control element mediating induction of the immediate-early gene set. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,DIV CLIN ONCOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA22042]; NIGMS NIH HHS [5 F32 GM14091-02] NR 64 TC 88 Z9 89 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 DEC PY 1992 VL 12 IS 12 BP 5288 EP 5300 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JZ258 UT WOS:A1992JZ25800002 PM 1448065 ER PT J AU CAI, H ERHARDT, P SZEBERENYI, J DIAZMECO, MT JOHANSEN, T MOSCAT, J COOPER, GM AF CAI, H ERHARDT, P SZEBERENYI, J DIAZMECO, MT JOHANSEN, T MOSCAT, J COOPER, GM TI HYDROLYSIS OF PHOSPHATIDYLCHOLINE IS STIMULATED BY RAS PROTEINS DURING MITOGENIC SIGNAL TRANSDUCTION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID KINASE-C; PHOSPHOLIPASE-C; GROWTH-FACTOR; PC12 CELLS; TYROSINE PHOSPHORYLATION; MEDIATED HYDROLYSIS; ADENYLATE-CYCLASE; ONCOGENIC RAS; DIACYLGLYCEROL; DIFFERENTIATION AB We have used a dominant inhibitory ras mutant (Ha-ras Asn-17) to investigate the relationship of Ras proteins to hydrolysis of phosphatidylcholine (PC) in the transduction of mitogenic signals. Expression of Ha-Ras Asn-17 inhibited NIH 3T3 cell proliferation induced by polypeptide growth factors or phorbol esters. In contrast, the mitogenic activity of PC-specific phospholipase C (PC-PLC) was not inhibited by Ha-Ras Asn-17 expression. Similarly, cotransfection with a cloned PC-PLC gene bypassed the block to NIH 3T3 cell proliferation resulting from expression of the inhibitory ras mutant. Hydrolysis of PC can therefore induce cell proliferation in the absence of normal Ras activity, suggesting that PC-derived second messengers may act downstream of Ras in mitogenic signal transduction. This was substantiated by the finding that Ha-Ras Asn-17 expression inhibited growth factor-stimulated hydrolysis of PC. Taken together, these results indicate that PC hydrolysis is a target of Ras during the transduction of growth factor-initiated mitogenic signals. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UAM CSIC,CTR BIOL MOLEC,E-28049 MADRID,SPAIN. UNIV TROMSO,INST MED BIOL,N-9001 TROMSO,NORWAY. RI Moscat, Jorge/A-7011-2009; Johansen, Terje/N-2971-2015 OI Johansen, Terje/0000-0003-1451-9578 FU NCI NIH HHS [R01 CA18689] NR 41 TC 59 Z9 59 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 DEC PY 1992 VL 12 IS 12 BP 5329 EP 5335 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JZ258 UT WOS:A1992JZ25800006 PM 1448068 ER PT J AU ALLITTO, BA MCCLATCHEY, AI BARNES, G ALTHERR, M WASMUTH, J FRISCHAUF, AM MACDONALD, ME GUSELLA, J AF ALLITTO, BA MCCLATCHEY, AI BARNES, G ALTHERR, M WASMUTH, J FRISCHAUF, AM MACDONALD, ME GUSELLA, J TI ASSAY BY POLYMERASE CHAIN-REACTION (PCR) OF MULTI-ALLELE POLYMORPHISMS IN THE HUNTINGTONS-DISEASE REGION OF CHROMOSOME-4 SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE POLYMERASE CHAIN REACTION; DNA POLYMORPHISM; HUNTINGTONS DISEASE ID LINKAGE DISEQUILIBRIUM; VNTR POLYMORPHISM; DNA MARKERS; GENE; RECOMBINATION; LOCALIZATION; D4S95 C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND. RP ALLITTO, BA (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114, USA. FU NHGRI NIH HHS [HG00169]; NINDS NIH HHS [NS16367] NR 32 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD DEC PY 1992 VL 6 IS 6 BP 513 EP 520 DI 10.1016/0890-8508(92)90048-3 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA KC019 UT WOS:A1992KC01900009 PM 1480191 ER PT J AU ROSENBERG, WS BREAKEFIELD, XO DEANTONIO, C ISACSON, O AF ROSENBERG, WS BREAKEFIELD, XO DEANTONIO, C ISACSON, O TI AUTHENTIC AND ARTIFACTUAL DETECTION OF THE E-COLI-LACZ GENE-PRODUCT IN THE RAT-BRAIN BY HISTOCHEMICAL METHODS SO MOLECULAR BRAIN RESEARCH LA English DT Article DE GENE DELIVERY; VIRAL VECTOR; BETA-GALACTOSIDASE; LACZ; LYSOSOME; X-GAL HISTOCHEMISTRY; CENTRAL NERVOUS SYSTEM; BRAIN; RAT ID GLYCOSYLATED BETA-GALACTOSIDASE; RETROVIRUS; NEURONS; CELLS; DELIVERY AB The accurate detection of a marker gene is fundamental to the assessment of any gene delivery protocol. The use of E. coli lacZ as such a marker gene has become common in studies on gene transfer to the central nervous system. The straightforward histochemical assay that is available to detect the gene product, beta-galactosidase, has made it an attractive system. However, using standard protocols, we have found dramatic non-E. coli lacZ staining in cells with neuronal, glial and endothelial morphology in the normal, adult rat brain. This false staining is primarily in the brainstem, but is evident in cortical and subcortical regions as well. This endogenous reactivity is independent of substrate concentration within the range tested, but is exquisitely sensitive to even small fluctuations in pH. In light of these findings, one must carefully examine any findings of E. coli lacZ gene expression in the rat brain based solely on histochemical analysis of tissue sections. C1 HARVARD UNIV,MCLEAN HOSP,SCH MED,NEUROREGENERAT LAB,MRC 119 BELMONT,BELMONT,MA 02178. HARVARD UNIV,SCH MED,NEUROSURG SERV,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,PROGRAM NEUROSURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02114. NR 20 TC 28 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC PY 1992 VL 16 IS 3-4 BP 311 EP 315 DI 10.1016/0169-328X(92)90240-C PG 5 WC Neurosciences SC Neurosciences & Neurology GA KG896 UT WOS:A1992KG89600018 ER PT J AU ABDELHAFIZ, HA HEASLEY, LE KYRIAKIS, JM AVRUCH, J KROLL, DJ JOHNSON, GL HOEFFLER, JP AF ABDELHAFIZ, HA HEASLEY, LE KYRIAKIS, JM AVRUCH, J KROLL, DJ JOHNSON, GL HOEFFLER, JP TI ACTIVATING TRANSCRIPTION FACTOR-II DNA-BINDING ACTIVITY IS STIMULATED BY PHOSPHORYLATION CATALYZED BY P42 AND P54 MICROTUBULE-ASSOCIATED PROTEIN-KINASES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID AMP RESPONSE ELEMENT; VIRUS TYPE-I; CYCLIC-AMP; DISTINCT; INTERACT; TYROSINE; CRE-BP1; CREB; ADENOSINE-3',5'-MONOPHOSPHATE; IDENTIFICATION AB Recent studies have detailed the ability of activating transcription factor-2 (ATF-2) to mediate adenoviral E1a stimulation of gene expression; however, an endogenous regulator for the transcriptional activity of this protein has not been described. To characterize the regulation of ATF-2 activity, we have expressed full-length and truncated peptides corresponding to various regions of the ATF-2 protein in bacteria and the baculovirus insect cell system. Bacterially expressed truncated (350-505) but not full-length ATF-2, was able to bind a consensus cAMP response element-containing oligonucleotide, suggesting the N-terminal moiety may serve as a negative regulator of DNA-binding activity. In contrast, the full-length ATF-2 protein expressed in Spodoptera frugiperda (Sf9) cells using a recombinant baculovirus was fully competent to bind DNA. Protein phosphatase 2A reversed the DNA-binding activity by dephosphorylating the ATF-2 polypeptide. Microtubule-associated protein kinase catalyzed the phosphorylation and stimulated the DNA-binding activity of bacterially expressed full-length ATF-2. Phosphopeptide mapping of phosphorylated ATF-2 proteins identified a single peptide in the N-terminal moiety of ATF-2 phosphorylated by p42 or p54 microtubule-associated protein kinase. Therefore, we propose that phosphorylation of this regulatory site is sufficient to induce an allosteric structural change in the ATF-2 protein, which allows dimerization and subsequent DNA binding. C1 UNIV COLORADO, HLTH SCI CTR,SCH MED,CTR CANC,DEPT MED, DIV MED ONCOL,B-171, DENVER, CO 80262 USA. UNIV COLORADO, SCH MED, CTR CANC, DEPT MED, DIV ENDOCRINOL, DENVER, CO 80262 USA. UNIV COLORADO, SCH MED, CTR CANC, DEPT MED, DIV RENAL MED, DENVER, CO 80262 USA. UNIV COLORADO, SCH MED, CTR CANC, DEPT BIOCHEM BIOPHYS & GENET, DENVER, CO 80262 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED, DIABET UNIT, BOSTON, MA 02129 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV, BOSTON, MA 02129 USA. NATL JEWISH CTR IMMUNOL & RESP MED, DIV BASIC SCI, DENVER, CO 80206 USA. FU NIDDK NIH HHS [DK-37871]; NIGMS NIH HHS [GM-45872, GM-30324] NR 35 TC 107 Z9 107 U1 0 U2 2 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 DEC PY 1992 VL 6 IS 12 BP 2079 EP 2089 DI 10.1210/me.6.12.2079 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KE801 UT WOS:A1992KE80100010 PM 1337144 ER PT J AU DASILVA, AJ YAMAMOTO, M ZALVAN, CH RUDD, CE AF DASILVA, AJ YAMAMOTO, M ZALVAN, CH RUDD, CE TI ENGAGEMENT OF THE TCR/CD3 COMPLEX STIMULATES P59FYN(T) ACTIVITY - DETECTION OF ASSOCIATED PROTEINS AT 72 KD AND 120-130 KD SO MOLECULAR IMMUNOLOGY LA English DT Article ID HUMAN LYMPHOCYTES-T; CELL ANTIGEN RECEPTOR; TYROSINE KINASE; SIGNAL TRANSDUCTION; CROSS-LINKING; CD4 RECEPTOR; P56LCK; IDENTIFICATION; ACTIVATION; AUTOPHOSPHORYLATION AB Engagement of the T cell antigen-receptor complex (TcR/CD3) induces the rapid tyrosine phosphorylation of a spectrum of substrates whose modification is crucial to the activation process. Although CD4-associated p56Ick and TcR/CD3-associated p59fyn(T) could account for this cascade, TcR/CD3 driven stimulation of p59fyn(T) activity has not been demonstrated. In this study, we confirm in Brij 96 based buffers that p59fyn(T) can be co-purified in association with the TcR/CD3 complex, and further demonstrate that antibody-induced cross-linking of TcR/CD3 on the cell surface results in a dramatic increase in the detection of receptor associated kinase activity. This results in an increased phosphorylation and detection of TcR/CD3-p59fyn(T) associated zeta (16-21 kD), p72 (72 kD) and p120/130 (120-130 kD) chains. A distinction between increased recruitment and/or activity of p59fyn(T) was not possible due to the fact that receptor associated p59fyn(T) could not be detected by immunoblotting. However, an alternative approach using membrane vesicles demonstrated an anti-CD3 mediated induced increase (2-5-fold) in the phosphorylation of the fyn kinase. Augmented catalytic activity was accompanied-by p59fyn(T) labelling at the autophosphorylation site Tyr420, consistent with stimulated fyn catalytic activity, as well as the phosphorylation of polypeptides at 18-20 (TcRzeta), 31, 90 and 130 kD. Stimulation of fyn activity implicates this kinase as a mediator of the tyrosine phosphorylation events originating from the TcR/CD3 complex. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA51887-02] NR 34 TC 60 Z9 60 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 1992 VL 29 IS 12 BP 1417 EP 1425 DI 10.1016/0161-5890(92)90215-J PG 9 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA JZ921 UT WOS:A1992JZ92100001 PM 1454062 ER PT J AU CORRALDEBRINSKI, M HORTON, T LOTT, MT SHOFFNER, JM BEAL, MF WALLACE, DC AF CORRALDEBRINSKI, M HORTON, T LOTT, MT SHOFFNER, JM BEAL, MF WALLACE, DC TI MITOCHONDRIAL-DNA DELETIONS IN HUMAN BRAIN - REGIONAL VARIABILITY AND INCREASE WITH ADVANCED AGE SO NATURE GENETICS LA English DT Article ID ALZHEIMERS-DISEASE; SKELETAL-MUSCLE; NUCLEAR-DNA; HUMAN-HEART; DAMAGE; CARDIOMYOCYTES; METABOLISM; DECLINE; TISSUES AB We have examined the role of somatic mitochondrial DNA (mtDNA) mutations in human ageing by quantitating the accumulation of the common 4977 nucleotide pair (np) deletion (mtDNA4977) in the cortex, putamen and cerebellum. A significant increase in the mtDNA4977 deletion was seen in elderly individuals. In the cortex, the deleted to total mtDNA ratio ranged from 0.00023 to 0.012 in 67-77 year old brains and up to 0.034 in subjects over 80. In the putamen, the deletion level ranged from 0.0016 to 0.010 in 67 to 77 years old up to 0.12 in individuals over the age of 80. The cerebellum remained relatively devoid of mtDNA deletions. Similar changes were observed with a different 7436 np deletion. These changes suggest that somatic mtDNA deletions might contribute to the neurological impairment often associated with ageing. C1 EMORY UNIV,SCH MED,DEPT GENET & MOLEC MED,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 40 TC 600 Z9 610 U1 4 U2 19 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 DEC PY 1992 VL 2 IS 4 BP 324 EP 329 DI 10.1038/ng1292-324 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA KB495 UT WOS:A1992KB49500019 PM 1303288 ER PT J AU STGEORGEHYSLOP, P HAINES, J ROGAEV, E MORTILLA, M VAULA, G PERICAKVANCE, M FONCIN, JF MONTESI, M BRUNI, A SORBI, S RAINERO, I PINESSI, L POLLEN, D POLINSKY, R NEE, L KENNEDY, J MACCIARDI, F ROGAEVA, E LIANG, Y ALEXANDROVA, N LUKIW, W SCHLUMPF, K TANZI, R TSUDA, T FARRER, L CANTU, JM DUARA, R AMADUCCI, L BERGAMINI, L GUSELLA, J ROSES, A MCLACHLAN, DC AF STGEORGEHYSLOP, P HAINES, J ROGAEV, E MORTILLA, M VAULA, G PERICAKVANCE, M FONCIN, JF MONTESI, M BRUNI, A SORBI, S RAINERO, I PINESSI, L POLLEN, D POLINSKY, R NEE, L KENNEDY, J MACCIARDI, F ROGAEVA, E LIANG, Y ALEXANDROVA, N LUKIW, W SCHLUMPF, K TANZI, R TSUDA, T FARRER, L CANTU, JM DUARA, R AMADUCCI, L BERGAMINI, L GUSELLA, J ROSES, A MCLACHLAN, DC TI GENETIC-EVIDENCE FOR A NOVEL FAMILIAL ALZHEIMERS-DISEASE LOCUS ON CHROMOSOME-14 SO NATURE GENETICS LA English DT Article ID LINKAGE ANALYSIS; MARKERS; RECOMBINATION; MUTATION; REGION AB Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score z = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected. C1 UNIV TORONTO, CTR RES NEURODEGENERAT DIS, DEPT PHYSIOL, TORONTO M5S 1A8, ONTARIO, CANADA. MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET LAB, BOSTON, MA 02129 USA. ACAD MED SCI, NATL RES CTR MENT HLTH, MOLEC BRAIN GENET LAB, MOSCOW 113152, USSR. UNIV FLORENCE, DEPT NEUROL, I-50121 FLORENCE, ITALY. UNIV TURIN, DEPT NEUROL, I-10126 TURIN, ITALY. DUKE UNIV, MED CTR, BRYAN ALZHEIMERS DIS RES CTR, DURHAM, NC 27710 USA. UNIV MILANO, SCH MED, DEPT NEUROSCI, I-20127 MILAN, ITALY. TOHOKU UNIV, SCH MED, DEPT NEUROL, SENDAI, MIYAGI 980, JAPAN. BOSTON UNIV, SCH MED, NEUROGENET LAB, BOSTON, MA 02118 USA. IST MEXICANO SEGURO SOCIAL, DEPT GENET, GUADALAJARA, MEXICO. ECOLE PRAT HAUTES ETUD, NEUROHISTOL LAB, F-75651 PARIS 13, FRANCE. CNR, SERV NEUROL, USSL 17, I-88046 LAMEZIA TERME, ITALY. UNIV MASSACHUSETTS, MED CTR, DEPT NEUROL, WORCESTER, MA 01655 USA. SANDOZ PHARMACEUT CORP, SANDOZ RES INST, E HANOVER, NJ 07936 USA. NINCDS, CLIN NEUROPHARMACOL SECT, BETHESDA, MD 20892 USA. UNIV TORONTO, CLARKE INST PSYCHIAT, DEPT PSYCHIAT, NEUROGENET SECT, TORONTO M5T 1R8, ONTARIO, CANADA. MT SINAI MED CTR, WEIN CTR, MIAMI BEACH, FL 33140 USA. RP STGEORGEHYSLOP, P (reprint author), UNIV TORONTO, CTR RES NEURODEGENERAT DIS, DEPT MED, DIV NEUROL, TORONTO M5S 1A8, ONTARIO, CANADA. RI Haines, Jonathan/C-3374-2012; Macciardi, Fabio/N-3768-2014; OI Macciardi, Fabio/0000-0003-0537-4266; Farrer, Lindsay/0000-0001-5533-4225; sorbi, sandro/0000-0002-0380-6670 NR 33 TC 365 Z9 370 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD DEC PY 1992 VL 2 IS 4 BP 330 EP 334 DI 10.1038/ng1292-330 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA KB495 UT WOS:A1992KB49500020 PM 1303289 ER PT J AU MIKATI, MA MAGUIRE, H BARLOW, CF OZELIUS, L BREAKEFIELD, XO KLAUCK, SM KORF, B OTUAMA, SLA DANGOND, F AF MIKATI, MA MAGUIRE, H BARLOW, CF OZELIUS, L BREAKEFIELD, XO KLAUCK, SM KORF, B OTUAMA, SLA DANGOND, F TI A SYNDROME OF AUTOSOMAL DOMINANT ALTERNATING HEMIPLEGIA - CLINICAL PRESENTATION MIMICKING INTRACTABLE EPILEPSY - CHROMOSOMAL STUDIES - AND PHYSIOLOGICAL INVESTIGATIONS SO NEUROLOGY LA English DT Article ID COMPLICATED MIGRAINE; DYSTONIA GENE; CHILDHOOD; FLUNARIZINE; SEIZURES; INFANCY; TOMOGRAPHY; 9Q32-34; SPECT AB We report the familial occurrence and apparent autosomal dominant inheritance of alternating hemiplegia of childhood. The proband, a 9-year-old boy, presented with developmental retardation, rare tonic-clonic seizures, and frequent episodes of flaccid alternating hemiplegia that had been presumed to represent postictal paralysis. The hemiplegia spells, which started in his first year, did not respond to multiple antiepileptics. Between attacks, there was choreoathetosis and dystonic posturing. Father, brother. paternal uncle, and paternal grandmother had similar histories of alternating hemiplegia. Investigations included negative CT, metabolic, and coagulation studies. EEG and SPECT Tc-99m exametazime scanning failed to reveal any significant slowing or any major changes in cortical perfusion during hemiplegia as compared with nonhemiplegic periods. The karyotype revealed a balanced reciprocal translocation, 46,XY,t(3;9)(p26;q34) in the patient, in all the affected living relatives, and in one apparently unaffected sibling. The asymptomatic mother had a normal karyotype. Analysis of DNA markers was consistent with the karyotype results. Both affected siblings were treated with and responded to flunarizine therapy, with a greater than 70% decrease in attack frequency. Documented flunarizine trough serum concentrations were 28.9 ng/ml in the proband and 6.6 ng/ml in his brother. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RP MIKATI, MA (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,DIV NEUROPHYSIOL,HUNNEWELL 2,BOSTON,MA 02115, USA. NR 43 TC 43 Z9 45 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1992 VL 42 IS 12 BP 2251 EP 2257 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA KC375 UT WOS:A1992KC37500002 PM 1361034 ER PT J AU NEUMEYER, AM DIGREGORIO, DM BROWN, RH AF NEUMEYER, AM DIGREGORIO, DM BROWN, RH TI ARTERIAL DELIVERY OF MYOBLASTS TO SKELETAL-MUSCLE SO NEUROLOGY LA English DT Article ID MUSCULAR-DYSTROPHY; SYSTEMIC DELIVERY; INJECTION; MDX AB One of the major limitations of myoblast implantation as a therapy for muscular disease is that multiple injections by intramuscular implantation may be required for widespread delivery of cells. Also, some sites (eg, the diaphragm) are relatively inaccessible to injection. As an alternative, we have undertaken intra-arterial administration of myoblasts. For these experiments, we used donor cell myoblasts from the immortal L6 cell line labeled with lacZ via the beta-gal-at-gal retrovirus. In our model, target rat skeletal muscle (tibialis anterior [TA]) was injured using 0.5 ml of 0.5% bupivacaine and 15 IU of hyaluronidase; saline was injected into the contralateral side as a control. We infused 3 x 10(6) lacZ-positive cells into the abdominal aorta of previously injured, immunosuppressed (cyclosporine A) rats. At 7, 14, and 28 days, TA, liver, heart, lung, and spleen were examined for lacZ staining. In both the injured and control muscles, a few differentiated, lacZ-positive muscle cells were present, both singly and in groups, at each time point. These studies demonstrate that genetically labeled, transformed myoblasts may migrate from the arterial circulation to muscle and fuse there to form differentiated muscle cells. It is conceivable that intraarterial delivery of myoblasts may have a role in the therapy of selected diseases of skeletal muscle. RP NEUMEYER, AM (reprint author), MASSACHUSETTS GEN HOSP,NEUROL SERV,DAY LAB NEUROMUSCULAR RES,E BLDG,149 5TH ST,BOSTON,MA 02114, USA. NR 19 TC 47 Z9 48 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC PY 1992 VL 42 IS 12 BP 2258 EP 2262 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA KC375 UT WOS:A1992KC37500003 PM 1461375 ER PT J AU KOVACHICH, GB ARONSON, CE BRUNSWICK, DJ AF KOVACHICH, GB ARONSON, CE BRUNSWICK, DJ TI EFFECT OF REPEATED ADMINISTRATION OF ANTIDEPRESSANTS ON SEROTONIN UPTAKE SITES IN LIMBIC AND NEOCORTICAL STRUCTURES OF RAT-BRAIN DETERMINED BY QUANTITATIVE AUTORADIOGRAPHY SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE ANTIDEPRESSANTS; 5-HT UPTAKE SITES; LIMBIC SYSTEM ID H-3 PAROXETINE BINDING; LOW-AFFINITY BINDING; LONG-TERM TREATMENT; RECOGNITION SITES; IMIPRAMINE BINDING; CEREBRAL-CORTEX; IMIPRAMINE BINDING; NOREPINEPHRINE UPTAKE; FILM AUTORADIOGRAPHY; CORTICAL MEMBRANES AB The binding of H-3-cyanoimipramine, a selective radioligand for the serotonin (5-HT) transporter, was measured by quantitative autoradiography on sections of rat brain to determine if 5-HT uptake sites are regulated by repeated administration of antidepressants. The drugs studied included selective inhibitors of the uptake of 5-HT (citalopram, sertraline) or norepinephrine (protriptyline). Also, effects of inhibitors of monoamine oxidase (MAO) that inhibit both type A and type B MAO (phenelzine), or just type B MAO (deprenyl), were investigated. In addition, the atypical antidepressant mianserin, which has antagonist properties at both alpha2 adrenoceptors and 5-HT2 receptors, was studied. A total of 19 limbic areas and 4 regions of the parietal cortex were quantitated. The binding of H-3-cyanoimipramine was increased (14% to 31%) by phenelzine and deprenyl in a total of 3 brain areas and decreased (15% to 21%) by sertraline in 4 brain areas. Citalopram, protriptyline, and mianserin produced no statistically significant effect in any brain region examined. The results indicate that different types of antidepressants do not exert consistent or substantial regulatory effect on the density of uptake sites for 5-HT in the limbic system or parietal cortex. C1 UNIV PENN,SCH VET MED,PHARMACOL LAB,PHILADELPHIA,PA 19104. UNIV PENN,SCH VET MED,TOXICOL LAB,PHILADELPHIA,PA 19104. RP KOVACHICH, GB (reprint author), UNIV PENN,DEPT PSYCHIAT,DEPT VET AFFAIRS MED CTR,NEUROPSYCHOPHARMACOL UNIT 151E,PHILADELPHIA,PA 19104, USA. FU NIDA NIH HHS [DA05137]; NIMH NIH HHS [MH29094] NR 62 TC 38 Z9 38 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 DEC PY 1992 VL 7 IS 4 BP 317 EP 324 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA JZ786 UT WOS:A1992JZ78600007 PM 1476595 ER PT J AU MUNTZ, HG BELL, DA LAGE, JM GOFF, BA FELDMAN, S RICE, LW AF MUNTZ, HG BELL, DA LAGE, JM GOFF, BA FELDMAN, S RICE, LW TI ADENOCARCINOMA INSITU OF THE UTERINE CERVIX SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID MICROINVASIVE ADENOCARCINOMA; INTRAEPITHELIAL NEOPLASIA; CARCINOMA INSITU; CONE BIOPSY; LESIONS; CONIZATION; DIAGNOSIS; DYSPLASIA; SITU AB Objective: To assess the diagnostic accuracy of cervical conization in women with adenocarcinoma in situ and to determine whether a select group of women could be managed by conization alone without hysterectomy. Methods: We retrospectively reviewed 40 cases of cervical adenocarcinoma in situ diagnosed on cervical conization. Results: Cervical conization revealed adenocarcinoma in situ alone in 15 women. Twenty-five women had adenocarcinoma in situ coexisting with squamous dysplasia (23) or microinvasive squamous cell carcinoma (two). Twenty-two women underwent hysterectomy after cone biopsy. Adenocarcinoma in situ was detected in the hysterectomy specimen in one of 12 women with uninvolved cone margins, versus seven of ten women with involved margins (P = .006); two of these seven women also had foci of invasive adenocarcinoma in the hysterectomy specimen. Conization was the only treatment for 18 selected women with adenocarcinoma in situ and uninvolved margins; all were relapse-free after a median interval of 3 years (range 1.5-5). Conclusions: Women with cervical adenocarcinoma in situ diagnosed by conization who have positive margins are at high risk of residual adenocarcinoma in situ and moderate risk of occult invasive adenocarcinoma; expectant management is not warranted. However, a cone biopsy with uninvolved margins can reliably guide subsequent therapy. Selected young women who desire preservation of fertility and have uninvolved margins probably can be managed by conization alone, but further study is required to establish the safety of this approach. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NR 28 TC 60 Z9 60 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1992 VL 80 IS 6 BP 935 EP 939 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA KA566 UT WOS:A1992KA56600009 PM 1448263 ER PT J AU DIESENHOUSE, MC PALAY, DA NEWMAN, NJ TO, K ALBERT, DM AF DIESENHOUSE, MC PALAY, DA NEWMAN, NJ TO, K ALBERT, DM TI ACQUIRED HETEROCHROMIA WITH HORNER SYNDROME IN 2 ADULTS SO OPHTHALMOLOGY LA English DT Article AB Background: Heterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome. Acquired heterochromia associated with lesions in the ocular sympathetic pathways in adulthood, however, is rare. Methods: Two cases are reported in which sympathectomy in adults resulted in ipsilateral Horner syndrome with heterochromia. In each case, pharmacologic testing with cocaine and hydroxyamphetamine was performed. Results: In both cases, sympathectomy occurred at the level of the second order neuron, but hydroxyamphetamine testing suggested at least partial third order neuron involvement. Conclusion: Acquired heterochromia can occur in adults. The partial response to hydroxyamphetamine in the two cases presented may reflect trans-synaptic degeneration of the postganglionic neuron. A reduction in trophic influences on iris melanocytes may have contributed to the observed heterochromia. C1 EMORY UNIV,SCH MED,DEPT OPHTHALMOL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT NEUROSURG,ATLANTA,GA 30322. MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. FU NEI NIH HHS [P30 EY06360] NR 9 TC 21 Z9 21 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 1992 VL 99 IS 12 BP 1815 EP 1817 PG 3 WC Ophthalmology SC Ophthalmology GA KE755 UT WOS:A1992KE75500020 PM 1480396 ER PT J AU MANKIN, HJ AF MANKIN, HJ TI THE ACADEMIC-ORTHOPEDIC-SOCIETY - SMALL BEGINNINGS SO ORTHOPEDICS LA English DT Editorial Material RP MANKIN, HJ (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPED SERV,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD DEC PY 1992 VL 15 IS 12 BP 1399 EP 1400 PG 2 WC Orthopedics SC Orthopedics GA KB503 UT WOS:A1992KB50300001 PM 1461823 ER PT J AU GORDON, BR AF GORDON, BR TI IMMUNOTHERAPY - RATIONALE AND MECHANISMS SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT SYMP ON A STEP-CARE APPROACH TO THE TREATMENT OF UPPER RESPIRATORY ALLERGY CY MAY 13, 1992 CL HARRISBURG, PA SP RHONE POULENC RORER PHARM ID GENERATION; ALLERGY AB Immunotherapy is defined as the controlled exposure to known allergens to reduce the severity of the allergic response. Although available since 1910, its exact mechanism of action is not known but may involve an increase in allergen-specific IgG antibodies, a decrease in IgE synthesis, and alteration in T-lymphocyte activity. Immunotherapy is indicated in patients with proven allergy who have significant symptoms. It may be used together with pharmacologic measures but is relatively contraindicated in patients receiving beta-blocker therapy. Immunotherapy may be continued during pregnancy and should not be initiated in patients with autoimmune diseases or in human immunodeficiency virus-positive patients. Selection of appropriate diagnostic tests is important. Before immunotherapy is considered, there are two recommended in vivo tests (combined prick and intradermal skin test, and skin end point titration) and two recommended in vitro tests (radioallergosorbent test [RAST] and enzyme-inked immunosorbent assays [ELISA]), all equally safe and sensitive. After appropriate test interpretation, treatment is initiated with slowly escalating doses of allergen. Effects are often apparent in 3 to 6 months and, after continuation for 3 to 5 years, patients usually achieve lasting benefit. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. CAPE COD HOSP,HYANNIS,MA. RP GORDON, BR (reprint author), HARVARD UNIV,CAMBRIDGE,MA 02138, USA. NR 24 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 1992 VL 107 IS 6 SU S BP 861 EP 865 PN 2 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA KE286 UT WOS:A1992KE28600009 PM 1470467 ER PT J AU ZHENG, QJ LEVITSKY, LL FAN, J CILETTI, N MINK, K AF ZHENG, QJ LEVITSKY, LL FAN, J CILETTI, N MINK, K TI GLYCOGENESIS IN THE CULTURED FETAL AND ADULT-RAT HEPATOCYTE IS DIFFERENTLY REGULATED BY MEDIUM GLUCOSE SO PEDIATRIC RESEARCH LA English DT Article ID LIVER-GLYCOGEN; SYNTHASE PHOSPHATASE; INSULIN BINDING; PHOSPHORYLASE; METABOLISM; ACTIVATION; SYNTHETASE; INACTIVATION; EXPRESSION; ISOZYMES AB We examined the glycogenic response to glucose in cultured fetal and adult rat hepatocytes. After a 48-h culture in Dulbecco's modified Eagle's medium, 1 mM glucose, insulin, and cortisol, cells were cultured for 4 h in serum-free medium containing glucose (1-30 mM) and U-C-14-glucose. Incorporation of C-14-glucose into glycogen was greater in fetal hepatocytes compared with adult hepatocytes at all glucose concentrations (p < 0.001). Net glycogenic rate in fetal cells was greatest between 1 and 8.3 mM (7.7- +/- 1.1-fold increase) compared with a 3.8 +/-0.6-fold increase in adult cells. In contrast, there was a 19.4- +/- 2.7-fold increase in glycogen accumulated between 8.3 and 30 mM glucose in the adult and a 1.6- +/- 0.1 -fold increase in the fetus. Total glycogen synthetase activity was higher in fetal than adult hepatocytes (p < 0.001), but the active a form was similar in fetal and adult hepatocytes. Glycogen synthase a/a+b was stimulated at 8.3 mM or greater glucose in fetal hepatocytes, and 5.7 mM or greater in adult hepatocytes (p < 0.05). Total phosphorylase did not change with medium glucose, but glycogen phosphorylase a/a+b decreased in adult hepatocytes incubated in 5.7 mM glucose or greater (p < 0.05). Fetal phosphorylase a/a+b was increased at 8.3 mM or greater glucose (p < 0.05). In contrast, both adult and fetal phosphorylase were activated by glycogen. A glucose-induced increase in active phosphorylase may induce the decrease in net glycogenic rate at high glucose in fetal hepatocytes. A substrate-controlled balance between synthesis and degradation permits appropriate but not excessive glycogen storage in the fetal hepatocyte. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT ENDOCRINE UNIT,709 WANG ACC,15 PARKMAN ST,BOSTON,MA 02114. UNIV CHICAGO,WYLER CHILDRENS HOSP,PRITZKER SCH MED,DEPT PEDIAT,CHICAGO,IL 60637. FU NICHD NIH HHS [HD22891] NR 51 TC 6 Z9 6 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD DEC PY 1992 VL 32 IS 6 BP 714 EP 718 DI 10.1203/00006450-199212000-00019 PG 5 WC Pediatrics SC Pediatrics GA JZ792 UT WOS:A1992JZ79200016 PM 1287563 ER PT J AU HALE, RL RANDALL, CL BECKER, HC TURNER, KP AF HALE, RL RANDALL, CL BECKER, HC TURNER, KP TI ASPIRIN PRETREATMENT REDUCES ETHANOL WITHDRAWAL SEVERITY IN A MOUSE MODEL OF BINGE DRINKING SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACETYLSALICYLIC ACID; ETHANOL WITHDRAWAL; PROSTAGLANDINS ID ESSENTIAL FATTY-ACIDS; INDUCED SLEEP TIME; PROSTAGLANDIN METABOLISM; INHIBITORS ANTAGONIZE; MOTOR IMPAIRMENT; INDOMETHACIN; MICE; ALCOHOLISM; HYPNOSIS; HANGOVER AB Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and indomethacin, which inhibit prostaglandin (PG) synthesis, have a pronounced effect on a broad range of ethanol (EtOH) actions. Given this, it is somewhat surprising that NSAID treatment has not been found to alter major signs of ethanol withdrawal. To date, the only effect found has been indirect, that is, NSAID treatment reduces the efficacy of PG precursor administration in the treatment of ethanol withdrawal via the inhibition of PG formation. However, in those studies reporting negative results NSAID administration was delayed until EtOH withdrawal. Studies demonstrating NSAID-related attenuation of other actions of EtOH have typically employed a pretreatment paradigm in which NSAIDs are administered prior to, not after, ethanol exposure. Thus, it may be that the point in the ethanol exposure/withdrawal episode at which NSAIDs are administered could be crucial in determining their effects of the ethanol withdrawal syndrome. To address this issue, we employed a multiple-exposure "binge drinking" model. On each of 6 treatment days, male BALB/c mice were injected subcutaneously with either acetylsalicylic acid (ASA, 150 mg/kg) or the buffer vehicle, followed 1 h later by either ethanol (4.0 g/kg) or saline (0.9%) by gavage. Ethanol withdrawal severity, as measured by handling-induced convulsions, was determined 2, 4, 6, 8, 10, 12, and 24 h after EtOH gavage. ASA pretreatment was found to significantly reduce handling-induced convulsions in ethanol-intubated animals. In fact, the attenuation was of such a magnitude that the ASA-pretreated ethanol group did not significantly differ in withdrawal severity from non-ethanol-exposed controls. This effect was not likely due to ASA-related alterations in ethanol pharmacokinetics. These findings have relevance for the understanding of the basic mechanisms underlying ethanol dependence, as well as the potential role of PGs in this phenomenon. C1 MED UNIV S CAROLINA, CHARLESTON, SC 29403 USA. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29403 USA. NR 29 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD DEC PY 1992 VL 43 IS 4 BP 1169 EP 1173 DI 10.1016/0091-3057(92)90499-6 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA JZ943 UT WOS:A1992JZ94300030 PM 1475301 ER PT J AU GALE, GR SMITH, AB JONES, MM SINGH, PK AF GALE, GR SMITH, AB JONES, MM SINGH, PK TI EVIDENCE OF ACTIVE-TRANSPORT OF CADMIUM COMPLEXING DITHIOCARBAMATES INTO RENAL AND HEPATIC CELLS INVIVO SO PHARMACOLOGY & TOXICOLOGY LA English DT Article ID TISSUE DISTRIBUTION; ORGAN DISTRIBUTION; CHELATING-AGENTS; EXCRETION; MOBILIZATION; DIETHYLDITHIOCARBAMATE; ANTAGONISTS; DEPOSITS; RATS; MICE AB A study was made of the effects of certain inhibitors of transport systems on the actions of four cadmium (Cd) complexing N,N-disubstituted dithiocarbamates (DTCs) in mobilizing murine renal and hepatic Cd in vivo. Probenecid, the prototypical antagonist of organic anion transport in the kidney, when given 1 hr prior to each DTC, sharply suppressed the DTC-induced reduction of renal Cd but was virtually without effect on mobilization of Cd from liver. Sulfinpyrazone, which blocks tubular reabsorption of uric acid and also inhibits transport of a variety of organic acids, inhibited markedly the mobilization of both renal and hepatic Cd by DTCs. Phlorizin, an inhibitor of tubular sugar reabsorption, did not affect the Cd mobilizing actions of DTCs in any consistent fashion. We propose that the high degree of selectivity of DTCs in mobilizing renal and hepatic Cd is dependent, at least in part, upon active transport of DTCs into these tissues via the organic anion transport systems. This report presents the first evidence that compounds of the (R)2NCSS- class may gain access to intracellular space by an active, carrier-mediated process. C1 MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29401. VANDERBILT UNIV,DEPT CHEM,NASHVILLE,TN 37235. VANDERBILT UNIV,CTR MOLEC TOXICOL,NASHVILLE,TN 37235. RP GALE, GR (reprint author), VET AFFAIRS MED CTR,RALPH H JOHNSON DEPT,109 BEE ST,CHARLESTON,SC 29401, USA. FU NIEHS NIH HHS [ES-02638] NR 25 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 0901-9928 J9 PHARMACOL TOXICOL JI Pharmacol. Toxicol. PD DEC PY 1992 VL 71 IS 6 BP 452 EP 456 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA KE063 UT WOS:A1992KE06300008 PM 1480554 ER PT J AU ZHANG, H SCHEIRER, DC FOWLE, WH GOODMAN, HM AF ZHANG, H SCHEIRER, DC FOWLE, WH GOODMAN, HM TI EXPRESSION OF ANTISENSE OR SENSE RNA OF AN ANKYRIN REPEAT-CONTAINING GENE BLOCKS CHLOROPLAST DIFFERENTIATION IN ARABIDOPSIS SO PLANT CELL LA English DT Article ID CELL-CYCLE CONTROL; DNA-BINDING SUBUNIT; NF-KAPPA-B; CHROMOSOMAL LOCATION; CONTROL PROTEINS; HOMEOBOX GENE; REL ONCOGENE; HO GENE; NOTCH; THALIANA AB The Arabidopsis AKR gene that encodes a protein with four ankyrin repeats (a 33-amino acid motif that appears in the 89K domain of the human protein ankyrin) was isolated and characterized. A short sequence outside the ankyrin repeats is similar to that of the protein of the Drosophila muscle segment homeobox (msh) gene. The expression of the AKR gene is light dependent, and transgenic Arabidopsis plants with two or more copies of an antisense or sense AKR construct became chlorotic in a developmentally regulated manner. The chlorotic phenotype was genetically transmitted to the next generation, although most chlorotic plants produced much less seed. Reduced presence of thylakoid membranes and loss of grana are found in the plastids of chlorotic leaves, indicating that antisense or sense AKR has blocked chloroplast differentiation. This study indicates the importance of ankyrin repeat-containing proteins, not only in yeast and animals, but in plants as well. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NORTHEASTERN UNIV,DEPT BIOL,BOSTON,MA 02115. NR 57 TC 59 Z9 66 U1 0 U2 0 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 1040-4651 J9 PLANT CELL JI Plant Cell PD DEC PY 1992 VL 4 IS 12 BP 1575 EP 1588 DI 10.1105/tpc.4.12.1575 PG 14 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA KE191 UT WOS:A1992KE19100013 PM 1281700 ER PT J AU BORODIC, GE CHENEY, M MCKENNA, M AF BORODIC, GE CHENEY, M MCKENNA, M TI CONTRALATERAL INJECTIONS OF BOTULINUM-A TOXIN FOR THE TREATMENT OF HEMIFACIAL SPASM TO ACHIEVE INCREASED FACIAL SYMMETRY SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID BLEPHAROSPASM; NERVE AB Six patients noted facial asymmetry after botulinum toxin injection for hemifacial spasm. Each patient was injected on the side contralateral to the spasms with 10 to 15 IU over the zygomatic major and minor muscles. Each patient noted improvement in facial symmetry in the resting position and dynamic facial movements. Five of the six patients desired this approach with subsequent injections. This injection method variation proved helpful in the managing of hemifacial weakness created by botulinum A toxin for this condition. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 12 TC 24 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 1992 VL 90 IS 6 BP 972 EP 977 DI 10.1097/00006534-199212000-00004 PG 6 WC Surgery SC Surgery GA KA578 UT WOS:A1992KA57800004 PM 1448532 ER PT J AU EHRLICH, HP KELLEY, SF AF EHRLICH, HP KELLEY, SF TI HYPERTROPHIC SCAR - AN INTERRUPTION IN THE REMODELING OF REPAIR - A LASER DOPPLER BLOOD-FLOW STUDY SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Soft-tissue dermal loss does not regenerate; instead, it is replaced with scar. The extent of scarring is directly related to the severity of tissue loss (in terms of volume and depth). Commonly, an acute dermal loss will heal with excessive scar, hyertrophic scar. A hypertrophic scar is elevated but is contained within the boundaries of the initial injury. Hypertrophic scars have a reddish appearance, indicating an elevated local circulation. A laser Doppler blood flow monitor was employed to measure blood flow changes in healed wounds. It was speculated that local circulation in a developing hypertrophic scar would be elevated. Patients with recently healed wound sites were monitored and exhibited an average blood flow reading of 365 +/- 325 mV (n = 131). This average value, ranging from 98 to 1450 mV, was 18 times greater than the average reading from normal skin, which was 43 +/- 13 mV (n = 212). Blood flow declined to 32 +/- 21 mV (n = 7) at 16 to 18 weeks (74 percent of normal skin values) in healed wounds that developed normal scar. However, a closed wound that developed into a hypertrophic scar had a blood flow reading of 148 +/- 78 mV (n = 59) at 16 to 18 weeks. This value was three times greater than in normal skin and four times greater than in normal scar. At 38 to 50 weeks postinjury, hypertrophic scar remained elevated (102 +/- 34 mV; n = 10). Hypertrophic scars sustain an elevated blood flow. Blood flow patterns recorded from debrided burns, grafts, or donor sites that advanced into hypertrophic scar supported the concept that hypertrophic scar occurs as a consequence of an interruption in the remodeling phase of repair. Blood flow declined in these patients between 7 and 13 week postinjury, indicating the onset of the remodeling phase of repair. However, at 9 to 15 weeks, blood flow began to rise again. The blood flow patterns of hypertrophic scar show an early reduction in blood flow followed by a secondary rise that is sustained for more than a year in some scars. C1 MASSACHUSETTS GEN HOSP,WOUND HEALING LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP EHRLICH, HP (reprint author), MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,51 BLOSSOM ST,BOSTON,MA 02114, USA. NR 6 TC 51 Z9 54 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD DEC PY 1992 VL 90 IS 6 BP 993 EP 998 DI 10.1097/00006534-199212000-00009 PG 6 WC Surgery SC Surgery GA KA578 UT WOS:A1992KA57800009 PM 1448535 ER PT J AU GANJU, RK SMILEY, ST BAJORATH, J NOVOTNY, J REINHERZ, EL AF GANJU, RK SMILEY, ST BAJORATH, J NOVOTNY, J REINHERZ, EL TI SIMILARITY BETWEEN FLUORESCEIN-SPECIFIC T-CELL RECEPTOR AND ANTIBODY IN CHEMICAL DETAILS OF ANTIGEN RECOGNITION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LYMPHOCYTES-T; LIGAND RECEPTOR INTERACTIONS; HAPTENS; MOLECULAR RECOGNITION ID AMINO-ACID SUBSTITUTIONS; 3-DIMENSIONAL STRUCTURE; HYPERVARIABLE REGIONS; SCANNING MUTAGENESIS; COMPLEX; PROTEINS; BINDING; GENES; IMMUNOGLOBULINS; CONFORMATION AB A computer-generated model of the single. chain variable ValphaVbeta fragment of the RFL3.8 T-cell receptor (TCR) specific for fluorescein served as a starting point for mutagenesis aimed at identification of its antigen-contacting residues. Selected backbone segments of the model representing regions of prominent sequence similarity between antibodies and TCRs were least-squares superimposed onto the corresponding segments of the crystallographically resolved 4-4-20 antibody complexed with its antigen, fluorescein. The superimposition placed the antibody-bound fluorescein molecule close to a cavity on the surface of the TCR model formed by the complementarity-determining region (CDR) loops. Some of the TCR cavity forming loops displayed sequence motifs related to canonical CDR loops previously found in antibodies. Six putative amino acid contacts were identified and single-chain TCRs with mutations at each of these positions were expressed in Escherichia coli, purified, refolded, and assayed for fluorescein binding. Five of the six mutations resulted in a loss of detectable binding. These RFL3.8 antigen combining site residues are distributed among the beta3, alpha1, and alpha2 CDR loops and show striking chemical similarity to the known fluorescein contact residues on 4-4-20. Thus, antibodies and TCRs are similar both in their overall architecture and in the chemical details of specific antigen recognition. C1 BRISTOL MYERS SQUIBB, DEPT MOLEC SCI, SEATTLE, WA 98121 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. BRISTOL MYERS SQUIBB, DEPT MACROMOLEC MODELING, PRINCETON, NJ 08543 USA. RP GANJU, RK (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, IMMUNOBIOL LAB, BOSTON, MA 02115 USA. NR 42 TC 32 Z9 32 U1 2 U2 5 PU NATL ACAD PRESS 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 DEC 1 PY 1992 VL 89 IS 23 BP 11552 EP 11556 DI 10.1073/pnas.89.23.11552 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KA903 UT WOS:A1992KA90300094 PM 1454847 ER PT J AU BARSKY, AJ AF BARSKY, AJ TI HYPOCHONDRIASIS AND OBSESSIVE-COMPULSIVE DISORDER SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID DEPRESSION; SYMPTOMS; CLASSIFICATION; AGORAPHOBIA; BELIEFS; ILLNESS; ANXIETY C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NR 49 TC 60 Z9 60 U1 10 U2 15 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1992 VL 15 IS 4 BP 791 EP 801 PG 11 WC Psychiatry SC Psychiatry GA KZ892 UT WOS:A1992KZ89200006 PM 1461796 ER PT J AU BAER, L JENIKE, MA AF BAER, L JENIKE, MA TI PERSONALITY-DISORDERS IN OBSESSIVE-COMPULSIVE DISORDER SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID DSM-III; FAMILY HISTORY; SCHIZOPHRENIA; CLASSIFICATION; RELIABILITY; FEATURES C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 38 TC 45 Z9 48 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1992 VL 15 IS 4 BP 803 EP 812 PG 10 WC Psychiatry SC Psychiatry GA KZ892 UT WOS:A1992KZ89200007 PM 1461797 ER PT J AU OTTO, MW AF OTTO, MW TI NORMAL AND ABNORMAL INFORMATION-PROCESSING - A NEUROPSYCHOLOGICAL PERSPECTIVE ON OBSESSIVE-COMPULSIVE DISORDER SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID GLUCOSE METABOLIC RATES; HEMISPHERIC-SPECIALIZATION; BASAL GANGLIA; THOUGHT SUPPRESSION; COMPUTED-TOMOGRAPHY; CEREBRAL LATERALITY; ANXIETY; EMOTION; MEMORY; REPLICATION C1 MASSACHUSETTS GEN HOSP,BEHAV THERAPY UNIT,BOSTON,MA 02114. NR 89 TC 74 Z9 74 U1 2 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1992 VL 15 IS 4 BP 825 EP 848 PG 24 WC Psychiatry SC Psychiatry GA KZ892 UT WOS:A1992KZ89200009 PM 1461799 ER PT J AU JENIKE, MA AF JENIKE, MA TI PHARMACOLOGICAL TREATMENT OF OBSESSIVE-COMPULSIVE DISORDERS SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID CONTROLLED CLINICAL-TRIAL; DOUBLE-BLIND; BUSPIRONE AUGMENTATION; PRIMARY DEPRESSION; LITHIUM-CARBONATE; ANTI-DEPRESSANT; L-TRYPTOPHAN; CLOMIPRAMINE; FLUOXETINE; FLUVOXAMINE C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 145 TC 37 Z9 37 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1992 VL 15 IS 4 BP 895 EP 919 PG 25 WC Psychiatry SC Psychiatry GA KZ892 UT WOS:A1992KZ89200014 PM 1461804 ER PT J AU MINDUS, P JENIKE, MA AF MINDUS, P JENIKE, MA TI NEUROSURGICAL TREATMENT OF MALIGNANT OBSESSIVE-COMPULSIVE DISORDER SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID FOLLOW-UP; CINGULOTOMY; TRACTOTOMY; SCALE C1 KAROLINSKA INST, DEPT PSYCHOL, S-10401 STOCKHOLM 60, SWEDEN. KAROLINSKA INST, DEPT NEUROSURG, S-10401 STOCKHOLM, SWEDEN. KAROLINSKA INST, DEPT PSYCHIAT, S-10401 STOCKHOLM 60, SWEDEN. UNIV TRONDHEIM, DEPT PSYCHIAT & BEHAV MED, TRONDHEIM, NORWAY. HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. NR 70 TC 63 Z9 64 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1992 VL 15 IS 4 BP 921 EP 938 PG 18 WC Psychiatry SC Psychiatry GA KZ892 UT WOS:A1992KZ89200015 ER PT J AU CASSEM, N AF CASSEM, N TI HACKETT,THOMAS,PAUL 1928-1988 - IN MEMORIAM SO PSYCHOSOMATICS LA English DT Item About an Individual RP CASSEM, N (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114, USA. NR 0 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 WIN PY 1992 VL 33 IS 1 BP 2 EP 3 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA GX673 UT WOS:A1992GX67300002 PM 1539098 ER PT J AU HERZOG, DB AF HERZOG, DB TI EATING DISORDERS - NEW THREATS TO HEALTH SO PSYCHOSOMATICS LA English DT Article ID ANOREXIA-NERVOSA; BULIMIA NERVOSA C1 MASSACHUSETTS GEN HOSP,EATING DISORDERS UNIT,BOSTON,MA 02114. RP HERZOG, DB (reprint author), HARVARD UNIV,SCH MED,PSYCHIAT,BOSTON,MA 02115, USA. NR 11 TC 5 Z9 5 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 WIN PY 1992 VL 33 IS 1 BP 10 EP 15 PG 6 WC Psychiatry; Psychology SC Psychiatry; Psychology GA GX673 UT WOS:A1992GX67300004 PM 1539091 ER PT J AU MURRAY, GB AF MURRAY, GB TI LIMBIC MUSIC SO PSYCHOSOMATICS LA English DT Article C1 MASSACHUSETTS GEN HOSP,PSYCHIAT CONSULTAT SERV,BOSTON,MA 02114. RP MURRAY, GB (reprint author), HARVARD UNIV,SCH MED,PSYCHIAT,BOSTON,MA 02115, USA. NR 27 TC 4 Z9 4 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 WIN PY 1992 VL 33 IS 1 BP 16 EP 23 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA GX673 UT WOS:A1992GX67300005 PM 1539097 ER PT J AU BARSKY, AJ AF BARSKY, AJ TI AMPLIFICATION, SOMATIZATION, AND THE SOMATOFORM DISORDERS SO PSYCHOSOMATICS LA English DT Article ID IRRITABLE BOWEL SYNDROME; PEPTIC-ULCER; PAIN; HYPOCHONDRIASIS C1 MASSACHUSETTS GEN HOSP,PRIMARY CARE PSYCHIAT UNIT,BOSTON,MA 02114. RP BARSKY, AJ (reprint author), HARVARD UNIV,SCH MED,PSYCHIAT,BOSTON,MA 02115, USA. NR 34 TC 195 Z9 197 U1 3 U2 15 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD WIN PY 1992 VL 33 IS 1 BP 28 EP 34 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA GX673 UT WOS:A1992GX67300007 PM 1539100 ER PT J AU SANDERS, KM STERN, TA OGARA, PT FIELD, TS RAUCH, SL LIPSON, RE EAGLE, KA AF SANDERS, KM STERN, TA OGARA, PT FIELD, TS RAUCH, SL LIPSON, RE EAGLE, KA TI DELIRIUM DURING INTRAAORTIC BALLOON PUMP THERAPY - INCIDENCE AND MANAGEMENT SO PSYCHOSOMATICS LA English DT Article ID ACUTE CONFUSIONAL STATES; MYOCARDIAL-INFARCTION; BYPASS-SURGERY; COMPLICATIONS C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CORONARY CARE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. UNIV MICHIGAN,DEPT PSYCHIAT,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SANDERS, KM (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT CONSULTAT LIASON SERV,BOSTON,MA 02114, USA. NR 29 TC 14 Z9 14 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 WIN PY 1992 VL 33 IS 1 BP 35 EP 44 PG 10 WC Psychiatry; Psychology SC Psychiatry; Psychology GA GX673 UT WOS:A1992GX67300008 PM 1539101 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI POSTVIRAL FATIGUE SYNDROME - JENKINS,R, MOWBRAY,JF SO PSYCHOSOMATICS LA English DT Book Review C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP GREENBERG, DB (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, 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 WIN PY 1992 VL 33 IS 1 BP 114 EP 116 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA GX673 UT WOS:A1992GX67300020 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI NEUROLOGICAL COMPLICATIONS OF CANCER-TREATMENT - ROTTENBERG,DA SO PSYCHOSOMATICS LA English DT Book Review C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP GREENBERG, DB (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, 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 WIN PY 1992 VL 33 IS 1 BP 114 EP 114 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA GX673 UT WOS:A1992GX67300019 ER PT J AU MURRAY, GB AF MURRAY, GB TI THE PSYCHOSES OF EPILEPSY - TRIMBLE,MR SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,PSYCHIAT,BOSTON,MA 02115. RP MURRAY, GB (reprint author), MASSACHUSETTS GEN HOSP,PSYCHIAT CONSULTAT SERV,BOSTON,MA 02114, USA. NR 3 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 WIN PY 1992 VL 33 IS 1 BP 116 EP 116 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA GX673 UT WOS:A1992GX67300021 ER PT J AU PONCELET, BP WEDEEN, VJ WEISSKOFF, RM COHEN, MS AF PONCELET, BP WEDEEN, VJ WEISSKOFF, RM COHEN, MS TI BRAIN PARENCHYMA MOTION - MEASUREMENT WITH CINE ECHO-PLANAR MR IMAGING SO RADIOLOGY LA English DT Article DE CEREBROSPINAL FLUID, MR; MAGNETIC RESONANCE (MR), CINE STUDY; MAGNETIC RESONANCE (MR), ECHO PLANAR AB With echo-planar magnetic resonance (MR) imaging, the authors measured the intrinsic pulsatile motion of brain parenchyma. Phase-sensitive, electrocardiography-gated, two-dimensional cine images were acquired throughout the cardiac cycle by using a spin-echo, blipped echo-planar MR pulse sequence. Transverse and coronal planes were obtained in 14 healthy volunteers. Corrections were made for gross head motion. Brain motion consisted of a rapid displacement in systole, with a slow diastolic recovery. The motion occurred chiefly in the cephalocaudal and lateral directions; the anteroposterior motions were relatively small. Cephalocaudal velocities increase with proximity to the foramen magnum. The lateral motion is mainly a compressive motion of the thalami. Brain parenchymal velocities were as high as 2 mm/sec caudally in the brain stem and 1.5 mm/sec medially in the thalami. Net parenchymal excursions were at most 0.5 mm. Phase-based echo-planar velocity measurements agreed well with echo-planar Fourier velocity zeugmatography measurements and were consistent with reported values. Velocity mapping with echo-planar imaging offers a rapid and flexible method of assessing the pulsation velocities of the human brain. RP PONCELET, BP (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,MGH NMR CTR,BLDG 149,13TH ST,BOSTON,MA 02129, USA. RI Cohen, Mark/C-6610-2011 OI Cohen, Mark/0000-0001-6731-4053 FU NHLBI NIH HHS [5RO1HC3937] NR 21 TC 179 Z9 179 U1 2 U2 7 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1992 VL 185 IS 3 BP 645 EP 651 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JZ347 UT WOS:A1992JZ34700010 PM 1438740 ER PT J AU SEVICK, RJ KANDA, F MINTOROVITCH, J ARIEFF, AI KUCHARCZYK, J TSURUDA, JS NORMAN, D MOSELEY, ME AF SEVICK, RJ KANDA, F MINTOROVITCH, J ARIEFF, AI KUCHARCZYK, J TSURUDA, JS NORMAN, D MOSELEY, ME TI CYTOTOXIC BRAIN EDEMA - ASSESSMENT WITH DIFFUSION-WEIGHTED MR IMAGING SO RADIOLOGY LA English DT Article DE BRAIN, EDEMA; BRAIN, MR; MAGNETIC RESONANCE (MR), DIFFUSION STUDY; MAGNETIC RESONANCE (MR), EXPERIMENTAL; MAGNETIC RESONANCE (MR), PULSE SEQUENCES; MAGNETIC RESONANCE (MR), TECHNOLOGY ID CEREBRAL-ISCHEMIA; T2-WEIGHTED MRI; WATER; HYPONATREMIA; VASOPRESSIN; PERFUSION; CATS; RATS; PERMEABILITY; TRANSPORT AB To determine whether cytotoxic brain edema is associated with a decrease in diffusion, it was induced in rats, in the absence of ischemia, with an established model of acute hyponatremic encephalopathy. Cytotoxic brain edema secondary to acute hyponatremia was induced with intraperitoneal injections of 2.5% dextrose in water and subcutaneous injection of arginine-vasopressin. Coronal spin-echo magnetic resonance (MR) images were obtained with and without strong diffusion-sensitizing gradients before and after induction of acute hyponatremia. The apparent diffusion coefficient (ADC) was measured at two coronal section locations. In hyponatremic rats, the brain ADC was significantly reduced (P = .0153 and .0001) and was positively correlated with increased total brain water content (P = .0011). Plots of ADC versus total brain water showed a statistically significant inverse linear relationship between ADC and increasing brain water at the anterior coronal section location. The results indicate that the ADC may be a sensitive indicator of cytotoxic brain edema and thus may enable quantitative evaluation of such edema with diffusion-weighted MR imaging. C1 SAN FRANCISCO VET AFFAIRS MED CTR,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT RADIOL,NEURORADIOL SECT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MED,DIV GERIATR,SAN FRANCISCO,CA 94143. RP SEVICK, RJ (reprint author), FOOTHILLS PROV GEN HOSP,MRI CTR,DEPT RADIOL SCI & DIAGNOST,1403 29TH ST NW,CALGARY T2N 2T9,ALBERTA,CANADA. NR 21 TC 195 Z9 209 U1 1 U2 4 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1992 VL 185 IS 3 BP 687 EP 690 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JZ347 UT WOS:A1992JZ34700016 PM 1438745 ER PT J AU ROSENTHAL, DI BARTON, NW MCKUSICK, KA ROSEN, BR HILL, SC CASTRONOVO, FP BRADY, RO DOPPELT, SH MANKIN, HJ AF ROSENTHAL, DI BARTON, NW MCKUSICK, KA ROSEN, BR HILL, SC CASTRONOVO, FP BRADY, RO DOPPELT, SH MANKIN, HJ TI QUANTITATIVE IMAGING OF GAUCHER DISEASE SO RADIOLOGY LA English DT Article DE BONE MARROW, CT; BONES, MR; BONES, RADIONUCLIDE STUDIES; GAUCHER DISEASE; SPLEEN, MR; XENON, RADIOACTIVE ID MARROW TRANSPLANTATION; REPLACEMENT THERAPY; BONE; CT AB Twenty-three patients with type 1 Gaucher disease were evaluated with a battery of quantitative imaging techniques. Plain radiographs were used to measure cortical thickness and Erlenmeyer flask deformity. Xenon-133 uptake was measured in scans of the lower extremities. Dual-energy quantitative computed tomography was used for calculation of trabecular bone and bone marrow fat content in the spine and long bones. Magnetic resonance (MR) imaging was performed to evaluate disease extent and three-dimensional splenic volume. MR images were also used to provide quantitative measurements of each vertebral fat fraction. Each imaging modality was correlated with the others as well as with the clinical history of skeletal complications and the hematocrit and acid phosphatase activity. There was a strong relationship between splenic volume and severity as measured clinically and with laboratory testing. The spinal fat fraction also correlated with these measures of disease severity and with the femoral fat fraction and xenon uptake. No measurement allowed discrimination of patients with from those without skeletal complications. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED,BOSTON,MA 02114. NIH,BETHESDA,MD 20892. RP ROSENTHAL, DI (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,15 PARKMAN ST,SUITE 515,BOSTON,MA 02114, USA. NR 19 TC 51 Z9 52 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 DEC PY 1992 VL 185 IS 3 BP 841 EP 845 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JZ347 UT WOS:A1992JZ34700048 PM 1438773 ER PT J AU SUIT, H SKATES, S TAGHIAN, A OKUNIEFF, P EFIRD, JT AF SUIT, H SKATES, S TAGHIAN, A OKUNIEFF, P EFIRD, JT TI CLINICAL IMPLICATIONS OF HETEROGENEITY OF TUMOR RESPONSE TO RADIATION-THERAPY SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE HETEROGENEITY; RADIATION SENSITIVITY; DOSE RESPONSE CURVE; GAMMA-FACTOR; SF2 ID ATAXIA-TELANGIECTASIA; INVITRO RADIOSENSITIVITY; RADIOBIOLOGICAL CHARACTERIZATION; MALIGNANT-MELANOMA; SURVIVAL CURVES; CELL-CARCINOMA; LOCAL-CONTROL; FIBROBLASTS; RADIOTHERAPY; CANCER AB Heterogeneity of response of tumor tissue to radiation clearly exists. Major parameters include histopathologic type, size (number of tumor rescue units (TRUs)), hemoglobin concentration, cell proliferation kinetics and immune rejection reaction by host. Further, normal and presumably tumor tissue response is altered in certain genetic diseases, e.g. ataxia telangiectasia. Any assessment of response of tumor tissue to a new treatment method or the testing of a new clinical response predictor is optimally based upon a narrow strata, viz., uniform with respect to known parameters of response, e.g. size, histological type. Even among tumors of such a clinically defined narrow strata, there will be residual heterogeneity with respect to inherent cellular radiation sensitivity, distributions of pO2, (SH), cell proliferation etc. The value of a response predictor of an individual tumor will be determined by the heterogeneity of values for these and or other characteristics and by the coefficient of variation (CV) of the measured values of the individual parameters. Heterogeneity of one or more parameters of response is reflected in the slope of the dose response curve for local control, viz. the greater the heterogeneity the less steep the slope. To examine for this effect, the slope of dose response curves for control of model tumors of 10(8) tumor rescue units (TRU) and the SF2 = 0.5 (survival fraction after a single dose of 2 Gy) has been used to assess the impact of inter- and intra-tumoral variation of SF2 on slope, defined as gamma50 values. The gamma50 is the increase in local control expressed in percent points for a one percentage increment in dose, at the mid-point on the dose-response curve. The gamma50 was 6.5 for CV = 0.0. For inter-tumoral CVs of 10%, 20% and 40%, the gamma50 rapidly decreased to 2.4, 1.3 and 0.7. Intra-tumoral variation was less important, viz., for CVs of 10%, 20%, and 40% the gamma50 values were reduced to 5.3, 3.8 and 2.2. Combining inter- and intra-tumoral variation reduced the gamma50 only slightly below that for inter-tumoral variation alone. For example, were the CV 10% for inter- and intra-tumoral variation, the gamma50 would be 2.1 as compared to 2.4 for inter-tumoral variation alone. The number of TRUs also affects slope, viz. gamma50 increased from 1 to 9.7 as the TRU number increased from 10(1) to 10(12) . However, the number of TRUs within a specified T stage would be expected to vary over a rather limited range, e.g. less-than-or-equal-to a factor of 10(1-2). Accordingly, the effect of heterogeneity with respect to TRU numbers would affect gamma50 to a lesser degree than the probable heterogeneity of cellular radiation sensitivity. The CVs for response of tumor and normal tissue in rodents (TCD50 of independent tumor systems or LD50 for different strains of mice) were in the range of 9-20%, i.e. less than found for SF2 of human tumor cells as determined in vitro, 20-50%. Were the gamma50 for a narrow strata of human tumors to be almost-equal-to 2, as judged likely, then the CV of radiation sensitivity of cells in vivo would be less-than-or-equal-to 10-15%, a value comparable with that found for independent tissue systems. RP SUIT, H (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 13311, CA 48096] NR 39 TC 103 Z9 104 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD DEC PY 1992 VL 25 IS 4 BP 251 EP 260 DI 10.1016/0167-8140(92)90244-O PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA KF594 UT WOS:A1992KF59400004 PM 1480770 ER PT J AU GLYNN, SM RANDOLPH, ET ETH, S PAZ, GG LEONG, GB SHANER, AL VANVORT, W AF GLYNN, SM RANDOLPH, ET ETH, S PAZ, GG LEONG, GB SHANER, AL VANVORT, W TI SCHIZOPHRENIC SYMPTOMS, WORK ADJUSTMENT, AND BEHAVIORAL FAMILY-THERAPY SO REHABILITATION PSYCHOLOGY LA English DT Article ID CONTROLLED TRIAL; MAINTENANCE CHEMOTHERAPY; COMMUNITY MANAGEMENT; SOCIAL-INTERVENTION; INTERNATIONAL-PILOT; AFTERCARE TREATMENT; MENTALLY-ILL; FOLLOW-UP; PREVENTION; MORBIDITY AB We investigated work adjustment among 41 recently exacerbated patients with schizophrenia who were randomly assigned to receive either customary care alone or behavioral family therapy (BFT) and customary care. At baseline, most patients were unemployed and evidenced poor work adjustment. Negative schizophrenic symptoms were more strongly associated with current work dysfunction than were indices of other psychopathology. At one year, significantly fewer patients participating in BFT had evidenced psychotic exacerbations. However, vocational adjustment in both groups was still poor, with few benefits of BFT on work functioning noted. RP GLYNN, SM (reprint author), W LOS ANGELES VA MED CTR B151J,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 45 TC 17 Z9 18 U1 4 U2 5 PU SPRINGER PUBL CO PI NEW YORK PA 536 BROADWAY, NEW YORK, NY 10010-3955 SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD WIN PY 1992 VL 37 IS 4 BP 323 EP 338 DI 10.1037//0090-5550.37.4.323 PG 16 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA KL228 UT WOS:A1992KL22800006 ER PT J AU GLAZER, WM FRIEDHOFF, LT MARDER, SR BROWN, WA AF GLAZER, WM FRIEDHOFF, LT MARDER, SR BROWN, WA TI THE DETERMINATION OF THE STEADY-STATE PHARMACOKINETIC PROFILE OF FLUPHENAZINE DECANOATE BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY DETECTION SO SCHIZOPHRENIA RESEARCH LA English DT Article DE FLUPHENAZINE DECANOATE; INJECTION VOLUME; PHARMACOKINETIC; (SCHIZOPHRENIA) ID SCHIZOPHRENIC-PATIENTS; PLASMA-LEVELS; NEUROLEPTICS AB This study uses the highly sensitive method of gas chromatography/mass spectrometry to compare the basic steady-state pharmacokinetic parameters of two fluphenazine decanoate formulations. Sixteen stable outpatients participated in a two-way crossover design study of the bioavailability of a new formulation of FPZ Dec, i.e., 10 mg/ml, to the standard 25 mg/ml formulation. When compared to a 1 ml injection of the standard formulation (25 mg/ml) over a two-week, steady-state period, we found bioequivalence as evidenced by similar mean areas under the curve (hrs x ng/ml). We did find that the injection volume of the same dose (2.5 ml of a 10 mg/ml formulation) results in a statistically significantly higher maximum serum level of parent fluphenazine. A tendency toward faster time to peak level was observed with the 10 mg/ml formulation but the difference was not statistically significant. Both of these differences are considered too small to be clinically significant. In a subgroup of 10 patients, pre-injection serum fluphenazine levels correlated significantly (Pearson r=0.78, p<0.05) with serum prolactin levels. C1 ESAI AMER GLENPOINTE CTR E, TEANECK, NJ USA. UNIV CALIF LOS ANGELES, SCH MED, W LOS ANGELES VA MED CTR, BRENTWOOD DIV, LOS ANGELES, CA USA. DEPT VET AFFAIRS MED CTR, PROVIDENCE, RI USA. RP GLAZER, WM (reprint author), YALE UNIV, SCH MED,CONNECTICUT MENTAL HLTH CTR,DEPT PSYCHIAT, TD CLIN, 34 PK ST, NEW HAVEN, CT 06519 USA. FU NIMH NIH HHS [MH30929] NR 15 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 1992 VL 8 IS 2 BP 111 EP 117 DI 10.1016/0920-9964(92)90026-2 PG 7 WC Psychiatry SC Psychiatry GA KC112 UT WOS:A1992KC11200003 PM 1457388 ER PT J AU MUELLER, PR DAWSON, SL AF MUELLER, PR DAWSON, SL TI ADVANCED IMAGING AND INTERVENTION IN TRANSPLANTATION - PREFACE SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Editorial Material RP MUELLER, PR (reprint author), MASSACHUSETTS GEN HOSP,DIV HEAD ABDOMINAL IMAGING & INTERVENT RADIOL,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 DEC PY 1992 VL 9 IS 4 BP UR7 EP UR7 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA KB953 UT WOS:A1992KB95300001 ER PT J AU JOHNSON, RA WHITE, M AF JOHNSON, RA WHITE, M TI SYPHILIS IN THE 1990S - CUTANEOUS AND NEUROLOGIC MANIFESTATIONS SO SEMINARS IN NEUROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SECONDARY SYPHILIS; HIV-INFECTION; TREPONEMA-PALLIDUM; SEROLOGIC RESPONSE; PATIENT; NEUROSYPHILIS; TESTS; ASSOCIATION; DIAGNOSIS C1 HARVARD UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BETH ISRAEL HOSP,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. NR 52 TC 12 Z9 12 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD DEC PY 1992 VL 12 IS 4 BP 287 EP 298 DI 10.1055/s-2008-1041185 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA KE817 UT WOS:A1992KE81700003 PM 1485038 ER PT J AU MACKOOL, BT FITZPATRICK, TB AF MACKOOL, BT FITZPATRICK, TB TI DIAGNOSIS OF NEUROFIBROMATOSIS BY CUTANEOUS EXAMINATION SO SEMINARS IN NEUROLOGY LA English DT Article ID VONRECKLINGHAUSEN NEUROFIBROMATOSIS; ELEPHANT-MAN; ORIGIN RP MACKOOL, BT (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA 02114, USA. NR 37 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 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD DEC PY 1992 VL 12 IS 4 BP 358 EP 363 DI 10.1055/s-2008-1041192 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA KE817 UT WOS:A1992KE81700010 PM 1485045 ER PT J AU ANTMAN, KH AF ANTMAN, KH TI CHEMOTHERAPY OF ADVANCED SARCOMAS OF BONE AND SOFT-TISSUE SO SEMINARS IN ONCOLOGY LA English DT Article ID HIGH-DOSE IFOSFAMIDE; PHASE-II TRIAL; GYNECOLOGIC ONCOLOGY GROUP; COMBINATION CHEMOTHERAPY; RANDOMIZED TRIAL; ADRIAMYCIN NSC-123127; UNRESECTABLE SARCOMA; MESNA UROPROTECTION; EFFECTIVE REGIMEN; GROUP EXPERIENCE RP ANTMAN, KH (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV MED,44 BINNEY ST,BOSTON,MA 02115, USA. NR 73 TC 29 Z9 30 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1992 VL 19 IS 6 SU 12 BP 13 EP 22 PG 10 WC Oncology SC Oncology GA KK166 UT WOS:A1992KK16600004 PM 1485169 ER PT J AU MONTANA, E BONNERWEIR, S WEIR, GC AF MONTANA, E BONNERWEIR, S WEIR, GC TI BETA-CELL MASS FALLS PROGRESSIVELY WHEN HYPERGLYCEMIA PERSISTS AFTER ISLET TRANSPLANTATION SO TRANSPLANTATION PROCEEDINGS LA English DT Article C1 NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. RP MONTANA, E (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK-35449, DK-36836] NR 3 TC 4 Z9 4 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 DEC PY 1992 VL 24 IS 6 BP 2996 EP 2996 PG 1 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA KC413 UT WOS:A1992KC41300288 PM 1466031 ER PT J AU POTTS, JT AF POTTS, JT TI MANAGEMENT OF ASYMPTOMATIC HYPERPARATHYROIDISM - A REPORT ON THE NIH CONSENSUS DEVELOPMENT CONFERENCE SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Editorial Material ID FRACTURES C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP POTTS, JT (reprint author), HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114, USA. NR 16 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 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 1992 VL 3 IS 10 BP 376 EP 379 DI 10.1016/1043-2760(92)90005-L PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KE821 UT WOS:A1992KE82100005 PM 18407125 ER PT J AU OETTINGER, MA AF OETTINGER, MA TI ACTIVATION OF V(D)J RECOMBINATION BY RAG1 AND RAG2 SO TRENDS IN GENETICS LA English DT Article ID SCID MUTATION; GENE; PROTEIN; EXPRESSION; SEQUENCE; BINDING; REPAIR; MOTIF; MOUSE AB V(D)J recombination is normally limited to lymphoid cells, but expression of the RAG1 and RAG2 genes allows other cell types to carry out this reaction. The products of these recently discovered genes may form part of the recombination machinery, and are a focal point for lymphoid development. RP OETTINGER, MA (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 28 TC 30 Z9 30 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD DEC PY 1992 VL 8 IS 12 BP 413 EP 416 DI 10.1016/0168-9525(92)90172-Z PG 4 WC Genetics & Heredity SC Genetics & Heredity GA KC475 UT WOS:A1992KC47500004 PM 1492366 ER PT J AU SMITH, CA DELUCA, NA AF SMITH, CA DELUCA, NA TI TRANSDOMINANT INHIBITION OF HERPES-SIMPLEX VIRUS GROWTH IN TRANSGENIC MICE SO VIROLOGY LA English DT Article ID REGULATORY PROTEIN ICP4; DNA-BINDING PROPERTIES; SHORT REPEAT REGION; ALPHA-GENES; VIRAL POLYPEPTIDES; TYPE-1; EXPRESSION; SEQUENCE; MUTANTS; GENOME C1 UNIV PITTSBURGH,SCH MED,DEPT MOLEC GENET & BIOCHEM,PITTSBURGH,PA 15261. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIAID NIH HHS [AI30612, AI27431] NR 37 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD DEC PY 1992 VL 191 IS 2 BP 581 EP 588 DI 10.1016/0042-6822(92)90233-F PG 8 WC Virology SC Virology GA JZ987 UT WOS:A1992JZ98700006 PM 1333114 ER PT J AU SWEADNER, KJ ARYSTARKHOVA, E AF SWEADNER, KJ ARYSTARKHOVA, E TI CONSTRAINTS ON MODELS FOR THE FOLDING OF THE NA,K-ATPASE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID ACTIVATED ADENOSINE-TRIPHOSPHATASE; AMINO-ACID-SEQUENCE; ALPHA-SUBUNIT; CATALYTIC SUBUNIT; OUTER MEDULLA; BETA-SUBUNIT; MONOCLONAL-ANTIBODY; TRYPTIC PEPTIDES; (NA,K)-ATPASE; MEMBRANE C1 HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. RP SWEADNER, KJ (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN 4,FRUIT ST,BOSTON,MA 02114, USA. NR 38 TC 20 Z9 20 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD NOV 30 PY 1992 VL 671 BP 217 EP 227 DI 10.1111/j.1749-6632.1992.tb43798.x PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KJ584 UT WOS:A1992KJ58400020 PM 1283814 ER PT J AU LEBEL, A HEDLEYWHYTE, ET DAVIS, KR CHAPMAN, PH AF LEBEL, A HEDLEYWHYTE, ET DAVIS, KR CHAPMAN, PH TI A 25-YEAR-OLD MAN WITH CHRONIC INTERMITTENT COCCYGEAL PAIN AND MILD BLADDER DYSFUNCTION - (TETHERED-CORD SYNDROME) OCCULT MYELOMENINGOCELE, WITH DERMAL SINUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID NEURAL-TUBE DEFECTS; SPINAL-CORD; SURGICAL FINDINGS; DYSRAPHISM; CHILDREN; LIPOMYELOMENINGOCELE; MENINGOMYELOCELE; LIPOMAS; BIFIDA; CONUS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP LEBEL, A (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 50 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 NOV 26 PY 1992 VL 327 IS 22 BP 1581 EP 1588 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA JZ432 UT WOS:A1992JZ43200008 ER PT J AU ANDREWS, DM KURNICK, JT RUOFF, KL AF ANDREWS, DM KURNICK, JT RUOFF, KL TI CASE-22-1992 - PATHOGENESIS OF CAT SCRATCH DISEASE - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP ANDREWS, DM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 4 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 NOV 26 PY 1992 VL 327 IS 22 BP 1600 EP 1601 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JZ432 UT WOS:A1992JZ43200021 ER PT J AU LU, XM FISCHMAN, AJ STEVENS, E LEE, TT STRONG, L TOMPKINS, RG YARMUSH, ML AF LU, XM FISCHMAN, AJ STEVENS, E LEE, TT STRONG, L TOMPKINS, RG YARMUSH, ML TI SN-CHLORIN E6 ANTIBACTERIAL IMMUNOCONJUGATES - AN INVITRO AND INVIVO ANALYSIS SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE IMMUNOCONJUGATE; PHOTOSENSITIZER; (ANTIBODY) ID ANTIBODY-TARGETED PHOTOLYSIS; NEUTRON-CAPTURE THERAPY; CYTO-TOXIC AGENTS; SINGLET OXYGEN; MONOCLONAL-ANTIBODIES; SENSITIZED PHOTOOXIDATION; IMAGING INFECTIONS; AMINES; IMMUNOGLOBULINS; HEMATOPORPHYRIN AB Monoclonal antibody-Sn-chlorin e6 immunoconjugates were prepared by the site-selective covalent modification of the monoclonal oligosaccharide moiety. By carefully controlling the reaction conditions and introducing triethanolamine groups as axial ligands of the Sn moiety, conjugates with in vivo biodistribution properties similar to underivatized IgG were prepared. By varying the reaction conditions, conjugates were reproducibly prepared with a range of photosensitizer to mAb molar ratios from 1.6 to 10. Based on a competitive inhibition radioimmunoassay, conjugates prepared by this method showed selectivity and binding affinity comparable to the unmodified antibody. The immunoconjugates had only slightly lower singlet oxygen yields than that observed with the Sn-chlorin e6 precursor indicating that negligible aggregation or structural modification of the chromophores occurred during the synthesis process. In vitro cell killing experiments demonstrated that all conjugates possessed significant cytotoxic activity. Biodistribution studies in mice showed that conjugates prepared with axial ligands had significant serum retention 24 h after injection while conjugates prepared without the triethanolamine ligand were much more rapidly cleared. In vivo specificity was demonstrated using rats infected with Fisher immunotype I P. aeruginosa at a site in the left posterior thigh muscle. Target to background ratios exceeded 60 at 120 h after conjugate injection of the specific immunoconjugate, compared to a ratio of only 6 for a non-specific mouse IgG conjugate. Biodistribution patterns at 120 h post injection indicate that the conjugates were both biologically active and structurally intact. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV NUCL MED,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. NR 51 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD NOV 25 PY 1992 VL 156 IS 1 BP 85 EP 99 PG 15 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA KA045 UT WOS:A1992KA04500011 PM 1431166 ER PT J AU SPERTINI, O SCHLEIFFENBAUM, B WHITEOWEN, C RUIZ, P TEDDER, TF AF SPERTINI, O SCHLEIFFENBAUM, B WHITEOWEN, C RUIZ, P TEDDER, TF TI ELISA FOR QUANTITATION OF L-SELECTIN SHED FROM LEUKOCYTES INVIVO SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE L-SELECTIN; SHEDDING; RECEPTOR; ELISA; LEUKOCYTE ID LYMPHOCYTE HOMING RECEPTOR; CELL-SURFACE MOLECULE; NODE HIGH ENDOTHELIUM; NEUTROPHIL ADHESION; CHEMOTACTIC FACTORS; RECOGNITION; PROTEINS; INVITRO; MAC-1; LEU-8 AB L-selectin is a cell surface receptor on granulocytes, lymphocytes and monocytes that is responsible for the initial attachment of leukocytes to endothelium. The extracellular domain Of L-selectin is proteolytically shed from leukocytes following cellular activation in vitro. The shed form of L-selectin (SL-selectin) is functionally active and at high concentrations can inhibit leukocyte attachment to endothelium. Therefore, an ELISA was developed to quantitate the levels Of SL-Selectin in biological fluids, biopsy specimens and during recombinant protein production. This simple, quantitative sandwich ELISA uses two monoclonal antibodies directed against the extracellular domain of SL-selectin. The assay has a detection range of 5-1300 ng/ml, is precise and sensitive. The ability of this assay to detect SL-selectin in serum, plasma, and culture supernatant fluid was demonstrated and it was used to quantitate circulating SL-selectin in normal and patient sera. Patients with sepsis and HIV infection showed markedly elevated SL-selectin levels in serum. Thus, the ELISA should prove useful both for laboratory purposes as well as in the diagnostic evaluation of patients with inflammatory diseases. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV CINCINNATI,MED CTR,SHRINERS BURN INST,CINCINNATI,OH 45267. UNIV MIAMI,SCH MED,DEPT PATHOL,MIAMI,FL 33101. FU NCI NIH HHS [CA-54464, CA-34183]; NIAID NIH HHS [AI-26872] NR 19 TC 114 Z9 116 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD NOV 25 PY 1992 VL 156 IS 1 BP 115 EP 123 DI 10.1016/0022-1759(92)90017-N PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA KA045 UT WOS:A1992KA04500014 PM 1385536 ER PT J AU MEYER, TE HABENER, JF AF MEYER, TE HABENER, JF TI CYCLIC-AMP RESPONSE ELEMENT BINDING-PROTEIN CREB AND MODULATOR PROTEIN CREM ARE PRODUCTS OF DISTINCT GENES SO NUCLEIC ACIDS RESEARCH LA English DT Note ID DNA-BINDING C1 MASSACHUSETTS GEN HOSP,HOWARD HUGHES MED INST,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 9 TC 30 Z9 32 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD NOV 25 PY 1992 VL 20 IS 22 BP 6106 EP 6106 DI 10.1093/nar/20.22.6106 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA KB049 UT WOS:A1992KB04900035 PM 1461747 ER PT J AU DUNN, DA LIN, VH KOCHEVAR, IE AF DUNN, DA LIN, VH KOCHEVAR, IE TI BASE-SELECTIVE OXIDATION AND CLEAVAGE OF DNA BY PHOTOCHEMICAL COSENSITIZED ELECTRON-TRANSFER SO BIOCHEMISTRY LA English DT Article ID INTERCALATED ETHIDIUM; PHOTODYNAMIC DAMAGE; REDOX PROCESSES; BINDING; MODEL; PHOTOSENSITIZATION; METHYLVIOLOGEN; PHOTOCLEAVAGE; DEGRADATION; PHOTOLYSIS AB A photochemical mechanism for single-strand cleavage of DNA is proposed in which a photoexcited intercalator transfers an electron to an externally bound cosensitizer. Once formed, the oxidized intercalator oxidizes an adjacent base, creating a charge-separated complex from which reactions leading to cleavage of the sugar-phosphate backbone occur in competition with back electron transfer. Using ethidium bromide (EB) as the intercalator and methyl viologen (MV) as the externally bound cosensitizer, a 10-fold enhancement in the rate of single-strand break formation was found in pBR322 DNA over that for EB alone using 488-nm excitation. The rate of cleavage correlated with the amount of MV bound to DNA. In accord with the expected redox properties of the one-electron-oxidized EB and the DNA bases, cleavage occurs selectively at guanines. Although the reaction proceeds in nitrogen-purged solutions, the rate of cleavage in air-saturated solutions was enhanced 2-fold. Treatment of irradiated samples with alkali leads to a 2-fold increase in the yield of single-strand breaks. These results support a mechanism in which cleavage occurs by selective oxidation of guanines in DNA, initiated by photochemical cosensitized electron transfer from intercalated EB to externally bound MV, and may provide a basis for the development of light-activated base-selective DNA cleaving agents. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. FU PHS HHS [223-89-1003] NR 32 TC 66 Z9 66 U1 2 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 24 PY 1992 VL 31 IS 46 BP 11620 EP 11625 DI 10.1021/bi00161a048 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JZ523 UT WOS:A1992JZ52300048 PM 1445897 ER PT J AU TSAI, LH AF TSAI, LH TI HOT PAPERS - MOLECULAR-BIOLOGY - ISOLATION OF THE HUMAN CDK2 GENE THAT ENCODES THE CYCLIN A-ASSOCIATED AND ADENOVIRUS E1A-ASSOCIATED P-33 KINASE BY TSAI,L.H., HARLOW,E., MEYERSON,M. SO SCIENTIST LA English DT Article AB A molecular biologist discusses his studies involving regulation of the onset of DNA synthesis. RP TSAI, LH (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV 23 PY 1992 VL 6 IS 23 BP 16 EP 16 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA JY794 UT WOS:A1992JY79400012 ER PT J AU WALKER, EM STONE, A MILLIGAN, LB GALE, GR ATKINS, LM SMITH, AB JONES, MM SINGH, PK BASINGER, MA AF WALKER, EM STONE, A MILLIGAN, LB GALE, GR ATKINS, LM SMITH, AB JONES, MM SINGH, PK BASINGER, MA TI MOBILIZATION OF LEAD IN MICE BY ADMINISTRATION OF MONOALKYL ESTERS OF MESO-2,3-DIMERCAPTOSUCCINIC ACID SO TOXICOLOGY LA English DT Article DE LEAD; MESO-2,3-DIMERCAPTOSUCCINIC ACID (DMSA); DMSA MONOESTERS; KIDNEY; BRAIN ID 2,3-DIMERCAPTOSUCCINIC ACID; DIMERCAPTOSUCCINIC ACID; INTOXICATION; CHILDREN; CADMIUM; AGENT AB The following six monoalkyl esters of meso-2,3-dimercaptosuccinic acid (DMSA) were synthesized and evaluated for relative activities in mobilizing lead from kidneys and brains of lead-bearing mice: n-propyl (Mn-PDMS), i-propyl (Mi-PDMS), n-butyl (Mn-BDMS), i-butyl (Mi-BDMS), n-amyl (Mn-ADMS) and i-amyl meso-2,3-dimercaptosuccinate (Mi-ADMS). DMSA was used as a positive control. When each was administered intraperitoneally (i.p.) as a single dose of 2.0 mmol/kg, DMSA lowered the kidney lead concentration 52%, while the monoesters effected reductions of 54-75%. Mn-ADMS was toxic at this dose. DMSA lowered the brain lead level 20% when given as a single dose, while the monoesters conferred reductions of 64-87%. When given as 5 daily i.p. injections at 0.5 mmol/kg, DMSA reduced the kidney lead concentration 45%, while the monoesters caused reductions of 56-73%. DMSA lowered the brain lead concentration 35% on the 5-day treatment regimen, while the monoesters evoked reductions of 59-75%. Mi-ADMS was equally effective when given orally or i.p. The i.p. LD50 value of this analog in mice is 3.0 mmol/kg, a value which lies between the reported LD50 doses of DMSA (16.0 mmol/kg) and dimercaprol (1.1 mmol/kg). It is suggested that the ability of these monoesters to cross cell membranes may account for their superiority to DMSA in mobilizing brain lead in this animal model. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,RES SERV,109 BEE ST,CHARLESTON,SC 29401. JOHN L MCCLELLAN MEM DEPT VET AFFAIRS MED CTR,LITTLE ROCK,AR 72205. UNIV ARKANSAS MED SCI HOSP,DEPT PATHOL,LITTLE ROCK,AR 72205. MED UNIV S CAROLINA,DEPT PHARMACOL,CHARLESTON,SC 29401. VANDERBILT UNIV,DEPT CHEM,NASHVILLE,TN 37235. VANDERBILT UNIV,CTR MOLEC TOXICOL,NASHVILLE,TN 37235. FU NIEHS NIH HHS [ES 02638-10] NR 20 TC 37 Z9 40 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD NOV 22 PY 1992 VL 76 IS 1 BP 79 EP 87 DI 10.1016/0300-483X(92)90020-F PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA KC108 UT WOS:A1992KC10800008 PM 1335621 ER PT J AU HEYDARI, AR RICHARDSON, A AF HEYDARI, AR RICHARDSON, A TI DOES GENE-EXPRESSION PLAY ANY ROLE IN THE MECHANISM OF THE ANTIAGING EFFECT OF DIETARY RESTRICTION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID LIVER PROTEIN-SYNTHESIS; AGE-RELATED DISEASE; FOOD RESTRICTION; SUPEROXIDE-DISMUTASE; METABOLIC-RATE; ANTIOXIDANT ENZYMES; CATALASE ACTIVITY; FISCHER RATS; AGING RATS; LIFE-SPAN C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,SAN ANTONIO,TX 78284. RP HEYDARI, AR (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284, USA. NR 67 TC 17 Z9 17 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD NOV 21 PY 1992 VL 663 BP 384 EP 395 DI 10.1111/j.1749-6632.1992.tb38682.x PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA KJ581 UT WOS:A1992KJ58100041 PM 1482068 ER PT J AU EPSTEIN, R AF EPSTEIN, R TI ANALYSIS OF NATURAL-HISTORY OF BREAST-CANCER IN YOUNG-WOMEN SO LANCET LA English DT Letter RP EPSTEIN, R (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BREAST EVALUAT CLIN,BOSTON,MA 02115, USA. NR 5 TC 5 Z9 5 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 NOV 21 PY 1992 VL 340 IS 8830 BP 1287 EP 1287 DI 10.1016/0140-6736(92)92985-O PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JZ237 UT WOS:A1992JZ23700026 PM 1359337 ER PT J AU ARONDEL, V LEMIEUX, B HWANG, I GIBSON, S GOODMAN, HM SOMERVILLE, CR AF ARONDEL, V LEMIEUX, B HWANG, I GIBSON, S GOODMAN, HM SOMERVILLE, CR TI MAP-BASED CLONING OF A GENE CONTROLLING OMEGA-3-FATTY-ACID DESATURATION IN ARABIDOPSIS SO SCIENCE LA English DT Article ID POLYMORPHISM LINKAGE MAP; THALIANA; DNA; METABOLISM; MUTANTS; PLASMID; PLANTS AB A gene from the flowering plant Arabidopsis thaliana that encodes an omega-3 desaturase was cloned on the basis of the genetic map position of a mutation affecting membrane and storage lipid fatty acid composition. Yeast artificial chromosomes covering the genetic locus were identified and used to probe a seed complementary DNA library. A complementary DNA clone for the desaturase was identified and introduced into roots of both wild-type and mutant plants by Ti plasmid-mediated transformation. Transgenic tissues of both mutant and wild-type plants had significantly increased amounts of the fatty acid produced by this desaturase. C1 MICHIGAN STATE UNIV, US DOE, PLANT RES LAB, E LANSING, MI 48824 USA. YORK UNIV, DEPT BIOL, N YORK M3J 1P3, ONTARIO, CANADA. HARVARD UNIV, SCH MED, DEPT GENET, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA. RI Somerville, Christopher/A-4048-2009 OI Somerville, Christopher/0000-0003-4647-0094 NR 24 TC 325 Z9 355 U1 2 U2 22 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 20 PY 1992 VL 258 IS 5086 BP 1353 EP 1355 DI 10.1126/science.1455229 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY958 UT WOS:A1992JY95800037 PM 1455229 ER PT J AU NABAVI, N FREEMAN, GJ GAULT, A GODFREY, D NADLER, LM GLIMCHER, LH AF NABAVI, N FREEMAN, GJ GAULT, A GODFREY, D NADLER, LM GLIMCHER, LH TI SIGNALING THROUGH THE MHC CLASS-II CYTOPLASMIC DOMAIN IS REQUIRED FOR ANTIGEN PRESENTATION AND INDUCES B7 EXPRESSION SO NATURE LA English DT Article ID CELL ACTIVATION ANTIGEN-B7; T-CELLS; COSTIMULATORY SIGNAL; RESTRICTED ANTIGEN; MOLECULES; RECEPTOR; TRANSLOCATION; INTERLEUKIN-2; INDUCTION; PROVIDES AB CLASS II major histocompatibility complex (MHC) molecules function as antigen-presenting elements as well as signal transducers on B lymphocytes. We previously reported that a B lymphoma cell transfectant, 5C2, expressing genetically engineered I-A(k) molecules with truncated cytoplasmic domains was severely impaired in both antigen presentation and in anti-Ia-induced intracytoplasmic signalling1-5. These two functions could be restored by preculturing 5C2 cells with cyclic AMP analogues6,7. Here we demonstrate that impaired signal transduction by truncated class II molecules results in a deficiency in induction of the newly defined B-cell accessory molecule B7 (ref. 8), which can be reversed by restoration of B7 expression. These data imply that contact of the T-cell antigen receptor with MHC/antigen ligand results in signal transmission through the class II cytoplasmic domain. This signal, which can be mimicked by dibutyryl cAMP, induces expression of B7, resulting in effective antigen presentation. The fact that crosslinking of surface class II MHC also induces B7 expression on normal resting human B cells9 supports this contention. C1 HARVARD UNIV,SCH PUBL HLTH,665 HUNTINGTON AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. ROCHE RES CTR,DEPT IMMUNOPHARMACOL,NUTLEY,NJ 07110. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR BIOL,BOSTON,MA 02115. NR 20 TC 328 Z9 329 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 19 PY 1992 VL 360 IS 6401 BP 266 EP 268 DI 10.1038/360266a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY960 UT WOS:A1992JY96000054 PM 1279442 ER PT J AU CANELLOS, GP ANDERSON, JR PROPERT, KJ NISSEN, N COOPER, MR HENDERSON, ES GREEN, MR GOTTLIEB, A PETERSON, BA AF CANELLOS, GP ANDERSON, JR PROPERT, KJ NISSEN, N COOPER, MR HENDERSON, ES GREEN, MR GOTTLIEB, A PETERSON, BA TI CHEMOTHERAPY OF ADVANCED HODGKINS-DISEASE WITH MOPP, ABVD, OR MOPP ALTERNATING WITH ABVD SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TERM FOLLOW-UP; COMBINATION CHEMOTHERAPY; PROGNOSTIC FACTORS; DACARBAZINE ABVD; BLEOMYCIN; VINBLASTINE; SURVIVAL; ADRIAMYCIN; TOXICITY; THERAPY AB Background and Methods. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) has been the standard treatment for Hodgkin's disease for almost 20 years. In a randomized, multicenter trial, we compared three regimens of primary systemic therapy for newly diagnosed advanced Hodgkin's disease in Stages IIIA2, IIIB, and IVA or IVB: (1) MOPP alone given for 6 to 8 cycles, (2) MOPP alternating with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for 12 cycles, and (3) ABVD alone for 6 to 8 cycles. Patients in a first relapse after radiation therapy were eligible. No additional radiation therapy was given. Patients who did not have a complete response or who had a relapse with either MOPP alone or ABVD alone were switched to the opposite regimen. Results. Of 361 eligible patients, 123 received MOPP, 123 received MOPP alternating with ABVD, and 115 received ABVD alone. The patients were stratified according to age, stage, previous radiation, histologic features, and performance status. The overall response rate was 93 percent, with complete responses in 77 percent: 67 percent in the MOPP group, 82 percent in the ABVD group, and 83 percent in the MOPP-ABVD group (P = 0.006 for the comparison of MOPP with the other two regimens, both of which contained doxorubicin). The rates of failure-free survival at five years were 50 percent for MOPP, 61 percent for ABVD, and 65 percent for MOPP-ABVD. Age, stage (III vs. IV), and regimen influenced failure-free survival significantly. Overall survival at five years was 66 percent for MOPP, 73 percent for ABVD, and 75 percent for MOPP-ABVD (P = 0.28 for the comparison of MOPP with the doxorubicin regimens). MOPP had more severe toxic effects on bone marrow than ABVD and was associated with greater reductions in the prescribed dose. Conclusions. In this trial, ABVD therapy for 6 to 8 months was as effective as 12 months of MOPP alternating with ABVD, and both were superior to MOPP alone in the treatment of advanced Hodgkin's disease. ABVD was less myelotoxic than MOPP or ABVD alternating with MOPP. C1 SUNY HLTH SCI CTR,DEPT MED,SYRACUSE,NY. UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV NEBRASKA,MED CTR,OMAHA,NE 68105. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RIGSHOSP,DEPT HEMATOL,DK-2100 COPENHAGEN,DENMARK. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT MED,WINSTON SALEM,NC 27103. US FDA,ROCKVILLE,MD 20857. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. RP CANELLOS, GP (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 31946] NR 29 TC 676 Z9 695 U1 1 U2 5 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 NOV 19 PY 1992 VL 327 IS 21 BP 1478 EP 1484 DI 10.1056/NEJM199211193272102 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA JY165 UT WOS:A1992JY16500002 PM 1383821 ER PT J AU AGNELLO, V CHUNG, RT KAPLAN, LM AF AGNELLO, V CHUNG, RT KAPLAN, LM TI A ROLE FOR HEPATITIS-C VIRUS-INFECTION IN TYPE-II CRYOGLOBULINEMIA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MIXED CRYOGLOBULINEMIA; RHEUMATOID-FACTOR; CROSS-IDIOTYPE; ANTIBODIES; ASSOCIATION; INTERFERON; DISEASES; CHAINS; HEAVY; ALPHA AB Background. Type II cryoglobulinemia is a vasculitis characterized by cryoglobulins consisting of complexes of polyclonal IgG and monoclonal IgM rheumatoid factors. The cause of these immune complexes is unknown, though both the hepatitis B (HBV) and C (HCV) viruses have been suspected. Methods. We studied 19 patients with Type II cryoglobulinemia for markers of HCV and HBV infection. Quantitative HCV antibody and RNA studies were performed on whole serum, cryoprecipitates, and supernatants. Results. Eight patients (42 percent) had HCV antibodies, and 16 (84 percent) had HCV RNA. Of the 19 patients, 5 (26 percent) had HBV markers, but only 1 had evidence of active HBV infection. Control serum samples from nine patients with Type I cryoglobulinemia were negative for HCV antibody and HCV RNA. There was a close, although not exclusive, association of one type of rheumatoid factor (WA) with HCV RNA. HCV antibody and HCV RNA were concentrated approximately 10-fold and 1000-fold, respectively, in the Type II cryoglobulins examined. Conclusions. Type II cryogiobulinemia is strongly associated with concomitant HCV infection and a high rate of false negative serologic tests. HCV virions and HCV antigen-antibody complexes are concentrated in the cryoprecipitates, most commonly in association with the WA type of rheumatoid factor, suggesting a role for HCV in the pathogenesis of mixed cryoglobulinemia. C1 MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. EDITH NOURSE ROGERS MEM VET AFFAIRS HOSP,BEDFORD,MA. RP AGNELLO, V (reprint author), LAHEY CLIN MED CTR,DEPT LAB MED,CLIN IMMUNOL LAB,41 MALL RD,BURLINGTON,MA 01805, USA. FU NIAMS NIH HHS [AR35487]; NIDDK NIH HHS [5T32DK07191, DK42189] NR 36 TC 1095 Z9 1114 U1 0 U2 4 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 NOV 19 PY 1992 VL 327 IS 21 BP 1490 EP 1495 DI 10.1056/NEJM199211193272104 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JY165 UT WOS:A1992JY16500004 PM 1383822 ER PT J AU CAMBRIA, RP AF CAMBRIA, RP TI HYPERTENSION AND RENAL-INSUFFICIENCY DUE TO RENOVASCULAR DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP CAMBRIA, RP (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 19 PY 1992 VL 327 IS 21 BP 1496 EP 1496 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JY165 UT WOS:A1992JY16500005 ER PT J AU BLOCH, KJ AF BLOCH, KJ TI CRYOGLOBULINEMIA AND HEPATITIS-C VIRUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ESSENTIAL MIXED CRYOGLOBULINEMIA; B VIRUS RP BLOCH, KJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 10 TC 39 Z9 39 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 NOV 19 PY 1992 VL 327 IS 21 BP 1521 EP 1522 DI 10.1056/NEJM199211193272111 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA JY165 UT WOS:A1992JY16500011 PM 1383823 ER PT J AU WEITZMAN, M GORTMAKER, SL SOBOL, AM PERRIN, JM AF WEITZMAN, M GORTMAKER, SL SOBOL, AM PERRIN, JM TI RECENT TRENDS IN THE PREVALENCE AND SEVERITY OF CHILDHOOD ASTHMA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CHANGING PATTERNS; BEHAVIOR PROBLEMS; NEW-ZEALAND; CHILDREN; MORTALITY; HOSPITALIZATION; RATES; HEALTH; RISKS AB Objective.-To examine changes in the prevalence and distribution of childhood asthma and its relationship with various measures of children's health and functioning between 1981 and 1988. It was hypothesized that there would be an increase in the prevalence of asthma, especially among black children, and that available measures would suggest a deterioration in the health and functioning of children with asthma over this period. Design.-Analyses of data from the Child Health Supplements to the National Health Interview Survey. Setting and Sample.-Nationally representative random sample of 15 224 children aged 0 to 17 years in 1981 and 17 110 in 1988. Main Outcome Measures.-Changes in (1) the prevalence and distribution of asthma, and (2) among children with asthma, the percentage of children hospitalized, days spent in bed, school days lost in the year prior to survey, and parent ratings and reports of children's overall health status and behavior problems. Results.-The estimated prevalence of childhood asthma increased from 3.1% in 1981 to 4.3% in 1988 (P<.0001), with similar increases for children, adolescents, and both sexes. Increases occurred among white children (2.7% to 4.1%; P<.0001) but not black children (5.3% vs 5.1%; not significant). Among those with asthma in 1988 compared with 1981, there was better overall health status (11% vs 24% fair/poor; P<.0001) and fewer with 30 or more days spent in bed in the last year (3.9% vs 7.2%; P<.04). We also observed trends toward a lower rate of hospitalization in the last year (10% vs 14%; P=.07), fewer school days missed (2% vs 6% with >30 days; P=.08), and a lower rate of extreme behavior problem scores (13% vs 18%; P=.09) in 1988 compared with 1981. Reductions were similar among both black and white children. Conclusions.-These results indicate that the estimated prevalence of asthma among children in the United States increased by almost 40%, and that although the increase occurred exclusively among white children, the prevalence of asthma still remains higher in black children than in white children. There was no support for increasing asthma severity and functional impact among either black or white children with asthma in 1988 compared with 1981. These findings provide no evidence to support the beliefs that asthma prevalence is increasing largely among black children or that the severity of asthma among most children in the United States is increasing. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT PEDIAT,ROCHESTER,NY 14642. HARVARD UNIV,SCH PUBL HLTH,DEPT BEHAV SCI,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. NR 40 TC 280 Z9 282 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 18 PY 1992 VL 268 IS 19 BP 2673 EP 2677 DI 10.1001/jama.268.19.2673 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA JX680 UT WOS:A1992JX68000029 PM 1304735 ER PT J AU HASHIMOTO, N GOLDSTEIN, BJ AF HASHIMOTO, N GOLDSTEIN, BJ TI DIFFERENTIAL REGULATION OF MESSENGER-RNAS ENCODING 3 PROTEIN-TYROSINE PHOSPHATASES BY INSULIN AND ACTIVATION OF PROTEIN-KINASE-C SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOSPHOTYROSINE PHOSPHATASE; SKELETAL-MUSCLE; XENOPUS OOCYTES; HEPATOMA-CELLS; HUMAN-PLACENTA; DIABETIC RATS; GROWTH-FACTOR; EXPRESSION; CLONING; IDENTIFICATION C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK36836, R01-DK43396] NR 31 TC 33 Z9 33 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 NOV 16 PY 1992 VL 188 IS 3 BP 1305 EP 1311 DI 10.1016/0006-291X(92)91373-X PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA JY446 UT WOS:A1992JY44600049 PM 1280135 ER PT J AU KOWAL, VO ADAMIS, AP ALBERT, DM AF KOWAL, VO ADAMIS, AP ALBERT, DM TI CONJUNCTIVAL CONCRETIONS SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Letter C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,CORNEA SERV,243 CHARLES ST,BOSTON,MA 02114. NR 5 TC 1 Z9 1 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV 15 PY 1992 VL 114 IS 5 BP 640 EP 641 PG 2 WC Ophthalmology SC Ophthalmology GA JX308 UT WOS:A1992JX30800025 PM 1443034 ER PT J AU ASCH, DA ENDE, J AF ASCH, DA ENDE, J TI THE DOWNSIZING OF INTERNAL-MEDICINE RESIDENCY PROGRAMS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE INTERNSHIP AND RESIDENCY; INTERNAL MEDICINE; EDUCATION, MEDICAL; FOREIGN MEDICAL GRADUATES; PHYSICIANS, FAMILY ID AMBULATORY CARE; HOUSE STAFF; EDUCATION; COSTS; WILL; PAY AB A variety of forces are converging to reduce the number of internal medicine residency positions offered in this country. This reduction, referred to as downsizing, has been proposed as the solution to several of the problems facing internal medicine. We examine the forces that underlie the current enthusiasm for downsizing; we consider the alternative strategies by which downsizing might be implemented; and we consider the implications of these alternatives on different groups of stakeholders. Although downsizing may represent a legitimate approach to real problems, any mechanism to reduce the number of training positions in internal medicine will have broad implications for medical education and patient care well into the next century. Special efforts must be taken to ensure that downsizing will not exacerbate the existing problems of overspecialization and limited access to care. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. RP ASCH, DA (reprint author), UNIV PENN,SCH MED,LEONARD DAVIS INST HLTH ECON,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104, USA. NR 30 TC 13 Z9 13 U1 2 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 NOV 15 PY 1992 VL 117 IS 10 BP 839 EP 844 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JX838 UT WOS:A1992JX83800008 PM 1416560 ER PT J AU STOLL, AL RENSHAW, PF SACHS, GS GUIMARAES, AR MILLER, C COHEN, BM LAFER, B GONZALEZ, RG AF STOLL, AL RENSHAW, PF SACHS, GS GUIMARAES, AR MILLER, C COHEN, BM LAFER, B GONZALEZ, RG TI THE HUMAN BRAIN RESONANCE OF CHOLINE-CONTAINING COMPOUNDS IS SIMILAR IN PATIENTS RECEIVING LITHIUM TREATMENT AND CONTROLS - AN INVIVO PROTON MAGNETIC-RESONANCE SPECTROSCOPY STUDY SO BIOLOGICAL PSYCHIATRY LA English DT Article ID H-1-NMR SPECTROSCOPY; HUMAN-ERYTHROCYTES; NMR-SPECTROSCOPY; THERAPY; PLASMA AB Lithium specifically and potentially inhibits membrane transport of choline. However, the effect of lithium on human neuronal choline content is unknown. This study was performed to determine if lithium alters the human brain choline concentration in vivo. In vivo proton magnetic resonance spectroscopy was used to compare the relative brain concentration of choline-containing compounds in seven lithium-treated patients and six lithium-free controls. No significant difference was observed in the mean relative choline resonance between the patient and control groups. Lithium treatment did not appear to alter the overall brain content of choline-containing compounds. It remains possible that a component of these compounds, particularly free choline, is elevated during lithium treatment. C1 HARVARD UNIV,SCH MED,HARVARD BIPOLAR RES GRP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MCLEAN BIPOLAR RES GRP,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,CTR NMR,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,DIV NEURORADIOL,BOSTON,MA 02114. MIT,DEPT NUCL ENGN,RADIOL SCI PROGRAM,CAMBRIDGE,MA 02139. RP STOLL, AL (reprint author), MCLEAN HOSP,MAILMAN RES CTR,MOLEC PHARMACOL LAB,115 MILL ST,BELMONT,MA 02178, USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 22 TC 31 Z9 31 U1 1 U2 1 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 NOV 15 PY 1992 VL 32 IS 10 BP 944 EP 949 DI 10.1016/0006-3223(92)90184-2 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KC871 UT WOS:A1992KC87100011 PM 1467379 ER PT J AU ANDREEFF, M STONE, R MICHAELI, J YOUNG, CW TONG, WP SOGOLOFF, H ERVIN, T KUFE, D RIFKIND, RA MARKS, PA AF ANDREEFF, M STONE, R MICHAELI, J YOUNG, CW TONG, WP SOGOLOFF, H ERVIN, T KUFE, D RIFKIND, RA MARKS, PA TI HEXAMETHYLENE BISACETAMIDE IN MYELODYSPLASTIC SYNDROME AND ACUTE MYELOGENOUS LEUKEMIA - A PHASE-II CLINICAL-TRIAL WITH A DIFFERENTIATION-INDUCING AGENT SO BLOOD LA English DT Article ID MURINE ERYTHROLEUKEMIA-CELLS; RETINOIC ACID; ERYTHROID DIFFERENTIATION; DIMETHYL-SULFOXIDE; MYELOID-LEUKEMIA; GENE-EXPRESSION; INDUCTION; COMMITMENT C1 MEM SLOAN KETTERING CANC CTR,DEPT MOLEC PHARMACOL,1275 YORK AVE,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT MED,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT CELL BIOL & GENET,NEW YORK,NY 10021. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PHARMACOL,PHARMACOL LAB,BOSTON,MA 02115. MAINE MED CTR,PORTLAND,ME 04102. FU NCI NIH HHS [CA08748] NR 30 TC 106 Z9 108 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 NOV 15 PY 1992 VL 80 IS 10 BP 2604 EP 2609 PG 6 WC Hematology SC Hematology GA JY677 UT WOS:A1992JY67700022 PM 1421378 ER PT J AU DREYFUSS, AI CLARK, JR ANDERSEN, JW AF DREYFUSS, AI CLARK, JR ANDERSEN, JW TI LIPID-ASSOCIATED SIALIC-ACID, SQUAMOUS-CELL CARCINOMA ANTIGEN, CARCINOEMBRYONIC ANTIGEN, AND LACTIC-DEHYDROGENASE LEVELS AS TUMOR-MARKERS IN SQUAMOUS-CELL CARCINOMA OF THE HEAD AND NECK SO CANCER LA English DT Article DE TUMOR MARKERS; HEAD AND NECK CANCER ID CANCER-PATIENTS; SERUM; TA-4; LOCALIZATION; DIAGNOSIS AB Background. Circulating tumor markers are valuable adjuncts in the management of several malignant lesions, including germ cell tumors and adenocarcinomas of the breast, colon, prostate, and ovary. However (to the authors' knowledge), currently, no serologic markers have been shown to have prognostic value for patients with squamous cell carcinomas of the head and neck (SCCHN). Methods. Novel and existing markers were evaluated prospectively in patients with SCCHN. The levels of lipid-associated sialic acids (LASA), squamous cell carcinoma circulating antigen (SCC-Ag), carcinoembryonic antigen (CEA), and lactic dehydrogenase (LDH) were evaluated in 52 patients: 42 with active measurable SCCHN and 10 with no clinical evidence of active disease after treatment (NED). Results. In patients with active disease, LASA, SCC-Ag, CEA, and LDH were elevated in 71%, 33%, 27%, and 18%, respectively, and in seven patients with distant metastasis (M1) in 100%, 86%, 57%, and 33%, respectively. None of the markers were elevated in the NED group. The incidence and magnitude of LASA and SCC-Ag elevations correlated with the extent of disease (active disease versus NED, Stage III versus IV, T0-3 versus T4 primary lesions, M0 versus M1). LDH and CEA elevations correlated primarily with the presence of distant metastases. Conclusions. LASA appears to be a promising sensitive marker of SCCHN, followed in decreasing order of sensitivity by SCC-Ag, CEA, and LDH. Additional study to evaluate the specificity of LASA and its correlation with tumor response to therapy is warranted. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. RP DREYFUSS, AI (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED,44 BINNEY ST,BOSTON,MA 02115, USA. NR 32 TC 17 Z9 17 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 NOV 15 PY 1992 VL 70 IS 10 BP 2499 EP 2503 DI 10.1002/1097-0142(19921115)70:10<2499::AID-CNCR2820701018>3.0.CO;2-# PG 5 WC Oncology SC Oncology GA JX894 UT WOS:A1992JX89400017 PM 1423179 ER PT J AU KORNBLITH, AB ANDERSON, J CELLA, DF TROSS, S ZUCKERMAN, E CHERIN, E HENDERSON, ES CANELLOS, GP KOSTY, MP COOPER, R WEISS, RB GOTTLIEB, A HOLLAND, JC AF KORNBLITH, AB ANDERSON, J CELLA, DF TROSS, S ZUCKERMAN, E CHERIN, E HENDERSON, ES CANELLOS, GP KOSTY, MP COOPER, R WEISS, RB GOTTLIEB, A HOLLAND, JC TI COMPARISON OF PSYCHOSOCIAL ADAPTATION AND SEXUAL FUNCTION OF SURVIVORS OF ADVANCED HODGKIN DISEASE TREATED BY MOPP, ABVD, OR MOPP ALTERNATING WITH ABVD SO CANCER LA English DT Article DE PSYCHOSOCIAL ADAPTATION; PSYCHOSEXUAL; HODGKIN DISEASE; CANCER SURVIVORS; MOPP; ABVD ID ILLNESS SCALE PAIS; CANCER SURVIVORS; TESTIS CANCER; TELEPHONE; CHEMOTHERAPY; INTERVIEW; ADJUSTMENT; CHILDHOOD; ANXIETY AB Background. Survivors of advanced Hodgkin disease, who were assigned randomly to treatment by mechlorethamine, vincristine, procarbazine, and prednisone (MOPP); doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD); or MOPP alternating with ABVD in a clinical trial of the Cancer and Leukemia Group B (protocol 8251), were compared in terms of their psychosocial adaptation and psychosexual function an average of 2.2 years after completion of treatment (range, 1-5 years). The study was undertaken to determine if there were differences among treatments in these functional areas as a consequence of differential long-term gonadal damage in the three regimens. Methods. Ninety-three disease-free survivors of advanced Hodgkin disease (56 men and 37 women) were studied (a minimum of 1 year after completion of treatment) by an interview conducted over the telephone. Standardized measures were used to assess their psychologic, sexual, family, and vocational functioning, including the following tests: the Psychosocial Adjustment to Illness Scale-Self Report, the Brief Symptom Inventory, the Profile of Mood States, and the Impact of Event Scale. Results. Contrary to expectation, no statistically significant differences in survivors' psychosocial adaptation or psychosexual function were found by treatment arm. Infertility (based on survivors' reports of medical test results and perceptions) and lower income 1 year before the diagnosis of cancer were significant predictors of poorer adjustment. Most survivors reported a range of problems that they attributed to having had cancer: 35%, proven or perceived infertility; 24%, sexual problems; 31%, health and life insurance problems; 26%, a negative socioeconomic effect; and 51%, conditioned nausea, associated with visual or olfactory reminders of chemotherapy. Conclusions. No significant long-term advantage in psychosocial adaptation or psychosexual function was found for survivors of Hodgkin disease treated by the less gonadally toxic ABVD regimen 1 to 5 years after completion of treatment. C1 UNIV NEBRASKA,MED CTR,OMAHA,NE 68105. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103. US FDA,ROCKVILLE,MD. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. SCRIPPS CLIN & RES FDN,SAN DIEGO,CA. BOWMAN GRAY MED CTR,WINSTON SALEM,NC. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. SUNY SYRACUSE,HLTH SCI CTR,SYRACUSE,NY. RP KORNBLITH, AB (reprint author), MEM SLOAN KETTERING CANC CTR,PSYCHIAT SERV,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA 03927, CA 32291, CA31946] NR 50 TC 49 Z9 49 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 NOV 15 PY 1992 VL 70 IS 10 BP 2508 EP 2516 DI 10.1002/1097-0142(19921115)70:10<2508::AID-CNCR2820701020>3.0.CO;2-V PG 9 WC Oncology SC Oncology GA JX894 UT WOS:A1992JX89400019 PM 1384949 ER PT J AU PIERCE, SM SCHNITT, SJ HARRIS, JR AF PIERCE, SM SCHNITT, SJ HARRIS, JR TI WHAT TO DO ABOUT MAMMOGRAPHICALLY DETECTED DUCTAL CARCINOMA INSITU SO CANCER LA English DT Editorial Material ID BREAST C1 BETH ISRAEL HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02215. BRIGHAM & WOMENS HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02215. NR 12 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 1992 VL 70 IS 10 BP 2576 EP 2578 DI 10.1002/1097-0142(19921115)70:10<2576::AID-CNCR2820701029>3.0.CO;2-3 PG 3 WC Oncology SC Oncology GA JX894 UT WOS:A1992JX89400028 PM 1330285 ER PT J AU TOGUCHIDA, J YAMAGUCHI, T RITCHIE, B BEAUCHAMP, RL DAYTON, SH HERRERA, GE YAMAMURO, T KOTOURA, Y SASAKI, MS LITTLE, JB WEICHSELBAUM, RR ISHIZAKI, K YANDELL, DW AF TOGUCHIDA, J YAMAGUCHI, T RITCHIE, B BEAUCHAMP, RL DAYTON, SH HERRERA, GE YAMAMURO, T KOTOURA, Y SASAKI, MS LITTLE, JB WEICHSELBAUM, RR ISHIZAKI, K YANDELL, DW TI MUTATION SPECTRUM OF THE P53 GENE IN BONE AND SOFT-TISSUE SARCOMAS SO CANCER RESEARCH LA English DT Article ID HEPATOCELLULAR-CARCINOMA; OSTEO-SARCOMA; T-ANTIGEN; WILD-TYPE; SUPPRESSOR; SEQUENCE; LEUKEMIA; PROTEIN; GROWTH; REARRANGEMENTS AB We present here an analysis of the spectrum of mutations of the p53 gene seen in 127 bone and soft tissue sarcomas of various histological classifications. Gross rearrangements were analyzed by Southern blotting using a complementary DNA probe from the p53 gene, and subtle alterations in the entire coding sequence (exons 2 through 11) were identified by a combination of single-strand conformation polymorphism analysis and direct genomic sequencing. A total of 42 somatic alterations of the p53 gene were found, of which 21 were gross rearrangements and 21 were subtle alterations. These included 17 cases of a single base substitution, 3 small deletions, and one single base insertion. In contrast to reported findings for other types of cancer, we found that mutations of the p53 gene in sarcomas are quite heterogeneous both in their distribution throughout the gene and in the type of genetic alterations that result. All 13 missense mutations we found occurred at highly conserved residues, whereas 8 nonsense mutations occurred at sites that spanned the gene from codons 46 to 316. Surprisingly, approximately one-half of the osteosarcomas with allelic deletions on 17p did not have detectable alterations in the coding sequence of the p53 gene. C1 MASSACHUSETTS EYE & EAR INFIRM,HOWE LAB OPHTHALMOL,ROOM 575,243 CHARLES ST,BOSTON,MA 02114. KYOTO UNIV,DEPT ORTHOPAED SURG,KYOTO 606,JAPAN. KYOTO UNIV,CTR RADIAT BIOL,KYOTO 606,JAPAN. UNIV ALBERTA,DEPT BIOCHEM,EDMONTON T6G 2H7,ALBERTA,CANADA. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV CHICAGO,MED CTR,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. NR 37 TC 302 Z9 306 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1992 VL 52 IS 22 BP 6194 EP 6199 PG 6 WC Oncology SC Oncology GA JX754 UT WOS:A1992JX75400010 PM 1423262 ER PT J AU FLETCHER, JA PINKUS, GS DONOVAN, K NAEEM, R SUGARBAKER, DJ MENTZER, S PINKUS, JL LONGTINE, J AF FLETCHER, JA PINKUS, GS DONOVAN, K NAEEM, R SUGARBAKER, DJ MENTZER, S PINKUS, JL LONGTINE, J TI CLONAL REARRANGEMENT OF CHROMOSOME BAND-6P21 IN THE MESENCHYMAL COMPONENT OF PULMONARY CHONDROID HAMARTOMA SO CANCER RESEARCH LA English DT Article ID GROWTH; TISSUE; TUMORS; LUNG AB Pulmonary chondroid hamartomas (PCH) are biphasic benign tumors that contain both mesenchymal and epithelial populations. In this report we describe two PCH in which clonal translocations at chromosome band 6p21 were demonstrated in mesenchymal cells. One of these had a unique translocation, t(6;14)(p21;q24), that was also found in one of two PCH karyotyped previously. The t(6;14) has not been described in other varieties of benign or malignant neoplasia. The 6p21 aberrations are of particular interest because break points in this chromosomal region appear to be characteristic of endometrial polyps. Endometrial polyps, like PCH, are biphasic benign tumors in which mesenchymal clonality has been demonstrated. C1 BRIGHAM & WOMENS HOSP,DIV THORAC SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP FLETCHER, JA (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [1K11CA01498-02] NR 24 TC 42 Z9 45 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1992 VL 52 IS 22 BP 6224 EP 6228 PG 5 WC Oncology SC Oncology GA JX754 UT WOS:A1992JX75400014 PM 1423265 ER PT J AU BUDACH, W HARTFORD, A GIOIOSO, D FREEMAN, J TAGHIAN, A SUIT, HD AF BUDACH, W HARTFORD, A GIOIOSO, D FREEMAN, J TAGHIAN, A SUIT, HD TI TUMORS ARISING IN SCID MICE SHARE ENHANCED RADIATION SENSITIVITY OF SCID NORMAL-TISSUES SO CANCER RESEARCH LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; ATAXIA-TELANGIECTASIA; DNA-REPAIR; MUTATION; RADIOSENSITIVITY; FIBROBLASTS; METASTASIS; SURVIVAL; GROWTH; MOUSE AB We addressed the question of whether cancers arising in an abnormally radiation sensitive normal tissue are also abnormally sensitive to ionizing irradiation. Germ line mutation-carrying mice with an enhanced radiation sensitivity of the normal tissue, the severe combined immunodeficient (SCID), and normally radiation sensitive mice (C3H) were used to study the sensitivity of normal and tumor tissues in vivo and in vitro. The lethal dose for 50% of the irradiated animals after single dose whole body irradiation was 2.6-fold higher in C3H compared to SCID mice. The dose for an isoeffective acute skin reaction after single dose irradiation was end point dependent 1.7 to 3.7 times higher in C3H than in SCID mice. Embryonic fibroblast and methylcholanthrene induced soft tissue sarcomas derived from C3H and SCID mice were established in vitro and colony-forming assays after single dose irradiation were carried out. Choosing mean inactivation dose as the end point, SCID fibroblast lines were 3.0-fold and SCID tumor cell lines 2.7-fold more radiation sensitive than C3H fibroblast lines and C3H tumor cell lines. Tumor control and growth delay assays for 110-mm3 tumors were used to compare the radiation sensitivity of SCID and C3H tumors in vivo. The doses for 50% local tumor control and a growth delay of 40 days were 2.6 times higher in C3H tumors compared to SCID tumors. Tumors arising in an abnormally radiation sensitive normal tissue are also sensitive to irradiation. The difference in radiation sensitivity of normal tissues predicted the difference in tumor tissues in these two murine systems. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114. NR 24 TC 43 Z9 43 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1992 VL 52 IS 22 BP 6292 EP 6296 PG 5 WC Oncology SC Oncology GA JX754 UT WOS:A1992JX75400025 PM 1423275 ER PT J AU PEREY, L HAYES, DF KUFE, D AF PEREY, L HAYES, DF KUFE, D TI EFFECTS OF DIFFERENTIATING AGENTS ON CELL-SURFACE EXPRESSION OF THE BREAST CARCINOMA-ASSOCIATED DF3-P EPITOPE SO CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY DF3; HUMAN-MILK; ANTIGEN; CANCER; MUCIN; GENE; GLYCOPROTEINS; SIALOMUCIN; RECEPTOR; PROTEIN AB The DF3 antigen is a member of a family of high-molecular-weight glycoproteins aberrantly expressed in human breast carcinomas. Recent work has described the generation of a monoclonal antibody (MAb), designated DF3-P, that reacts with immature, underglycosylated precursors of DF3 antigen. Immunoperoxidase staining studies have demonstrated that MAb DF3-P exhibits selective reactivity with malignant mammary epithelium. Using flow cytometry and live cell radioimmunoassays, the present studies demonstrate that the epitope recognized by MAb DF3-P is expressed on the surface of MCF-7 and other human breast carcinoma cell lines. We also demonstrate that treatment of MCF-7 cells with 12-O-tetradecanoylphorbol-13-acetate, an agent known to induce a more differentiated mammary cell phenotype, is associated with increased expression of the DF3-P epitope. Similar findings were obtained with sodium butyrate. The results indicate that these agents increase both cell surface DF3-P antigen density and the percentage of DF3-P-positive cells. Immunofluorescence studies performed on chamber slides further demonstrate that MAb DF3-P-reactive cells are detectable in small clones or clusters. Similar studies with 12-O-tetradecanoylphorbol-13-acetate- and butyrate-treated cells demonstrate increases in the size and number of these clusters. Taken together, these results indicate that the DF3-P epitope is expressed on the surface of human breast carcinoma cell lines and that the heterogeneity of this expression is related to the presence of differentiating signals. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,CLIN PHARMACOL LAB,44 BINNEY ST,BOSTON,MA 02115. NR 25 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1992 VL 52 IS 22 BP 6365 EP 6370 PG 6 WC Oncology SC Oncology GA JX754 UT WOS:A1992JX75400037 PM 1384960 ER PT J AU RHODES, CJ LINCOLN, B SHOELSON, SE AF RHODES, CJ LINCOLN, B SHOELSON, SE TI PREFERENTIAL CLEAVAGE OF DES-31,32-PROINSULIN OVER INTACT PROINSULIN BY THE INSULIN SECRETORY GRANULE TYPE-II ENDOPEPTIDASE - IMPLICATIONS OF A FAVORED ROUTE FOR PROHORMONE PROCESSING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATT20 CELLS; BETA-CELL; CONVERSION; SITE; KEX2; CDNA; RAT; PC2; IDENTIFICATION; SEQUENCE AB Two Ca2+-dependent endopeptidase activities are involved in proinsulin to insulin conversion: type I cleaves COOH-terminal to proinsulin Arg31-Arg32 (B-chain/C-peptide junction); and type II preferentially cleaves at the Lys64-Arg65 site (C-peptide/A-chain junction). To further understand the mechanism of proinsulin processing, we have investigated types I and II endopeptidase processing of intact proinsulin in parallel to that of the conversion intermediates, des31,32-proinsulin and des-64,65-proinsulin. The type I processed des-64,65-proinsulin and proinsulin at the same rate. In contrast, the type II endopeptidase processed des-31,32-proinsulin at a much faster rate (> 19-fold; p < 0.001) than it did intact proinsulin. Furthermore, unlabeled proinsulin concentrations required for competitive inhibition of I-125-labeled des-64,65-proinsulin and I-125-proinsulin processing by a purified insulin secretory granule lysate were similar (ID50 = 14-16 muM), whereas inhibition of I-125-labeled des-31,32-proinsulin processing required a higher nonradiolabeled proinsulin concentration (ID50 = 197 muM). Synthetic peptides corresponding to the sequences surrounding Lys64-Arg65 (AC-peptide/substrate) and Arg31-Arg32 (BC-peptide/substrate) of human proinsulin were synthesized for use as specific substrates or competitive inhibitors. Cleavage of the BC-substrate by type I and AC-substrate by type II was COOH-terminal of the dibasic sequence, with similar Ca2+- and pH requirements previously observed for proinsulin cleavage. Apparent K(m) and V(max) for type I processing of the BC-substrate was K(m) = 20 muM; V(max) = 22.8 pmol/min, and for type II processing of the AC-substrate was K(m) = 68 muM; V(max) = 97 pmol/min. In competitive inhibition assays, the BC-peptide similarly blocked insulin secretory granule lysate processing of des-64,65-proinsulin and proinsulin (ID50 = 45-55 muM), but did not inhibit des-31,32-proinsulin processing. However, the AC-peptide preferentially inhibited insulin secretory granule lysate processing of des-31,32-proinsulin (ID50 = 83 muM) compared to proinsulin (ID50 = 330 muM), and not des-64,65-proinsulin. We conclude that the type I endopeptidase recognized des-64,65-proinsulin and proinsulin as similar substrates, whereas the type II endopeptidase has a stronger preference for des-31,32-proinsulin compared to intact proinsulin. Furthermore, we suggest that in intact proinsulin there exists a constraint to efficient processing that is relieved following type I processing. Structural flexibility, in addition to the presence of Lys64 -Arg65, therefore appears to be important for type II endopeptidase specificity and may provide a molecular basis for a preferential route of proinsulin conversion via des-31,32-proinsulin. RP RHODES, CJ (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,EP JOSLIN RES LAB,1 JOSLIN PL,BOSTON,MA 02115, USA. FU NCRR NIH HHS [BRGS07RR05673]; NIDDK NIH HHS [DK36836] NR 42 TC 81 Z9 82 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 NOV 15 PY 1992 VL 267 IS 32 BP 22719 EP 22727 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JY163 UT WOS:A1992JY16300007 PM 1429623 ER PT J AU MAYTIN, EV AF MAYTIN, EV TI DIFFERENTIAL-EFFECTS OF HEAT-SHOCK AND UVB LIGHT UPON STRESS PROTEIN EXPRESSION IN EPIDERMAL-KERATINOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMALIAN-CELLS; DNA DAMAGE; ULTRAVIOLET-RADIATION; HUMAN-FIBROBLASTS; MESSENGER-RNA; RODENT CELLS; IRRADIATION; THERMOTOLERANCE; PURIFICATION; INDUCTION AB Heat stress and ultraviolet light in the UVB range ("sunburn spectrum," 290-320 nm) were found to alter the synthesis of specific proteins in cultured keratinocytes derived from mouse skin. Using giant two-dimensional gels, approximately 2,000 cellular polypeptides labeled with [S-35]methionine at 4-5 h after exposure to heat or to UVB were analyzed. Cells conditioned at sublethal temperatures (42-degrees-C for 1 h, or 47-degrees-C for 15 min) developed thermotolerance, while cells conditioned with UVB did not develop thermotolerance. Under these heat or UVB conditions, 19 stress proteins were observed. Proteins fell into three classes based upon their inducibility by heat or UVB, dose-response, and induction mechanism (transcriptional versus post-transcriptional) as defined by metabolic blockade with cordycepin (3'-deoxyadenosine). Class 1 proteins were inducible only by heat shock. They included three major heat-shock proteins (hsp 72, hsp 78, hsp 90) and a 42.5-kDa, pI 5.43 protein, and all were induced at the transcriptional level. Class 2 proteins were inducible by heat and by UVB. These included hsp 110 and eight additional polypeptides. All but one were affected by heat at the post-transcriptional level and were induced by UVB at both low (20 mJ/cm2) and high (80 mJ/cm2) doses. Class 3 proteins were inducible only at high UVB doses (survival < 10%). Class 1 and Class 2 proteins could be functionally involved in thermotolerance, while Class 3 proteins are more likely related to damage or cell death. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP MAYTIN, EV (reprint author), MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,DEPT DERMATOL,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NIAMS NIH HHS [5T32AR07098-15] NR 62 TC 52 Z9 53 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 NOV 15 PY 1992 VL 267 IS 32 BP 23189 EP 23196 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JY163 UT WOS:A1992JY16300075 PM 1429666 ER PT J AU CARRERA, AC WEE, SB ROBERTS, TM PARDOLL, DM AF CARRERA, AC WEE, SB ROBERTS, TM PARDOLL, DM TI SELECTIVE ASSOCIATION BETWEEN MHC CLASS I-RESTRICTED T-CELL RECEPTORS, CD8, AND ACTIVATED TYROSINE KINASES ON THYMOCYTES UNDERGOING POSITIVE SELECTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIGNAL TRANSDUCTION; ANTIGEN RECEPTOR; ZETA-CHAIN; TRANSGENIC MICE; P56LCK; EXPRESSION; COMPLEX; THYMUS; DOMAIN; PHOSPHORYLATION AB Developing T cells undergo distinct selection processes that determine the TCR repertoire. Positive selection involves the differentiation of immature thymocytes capable of recognizing antigens complexed with self-MHC molecules to mature T cells. Besides the central role of TCR engagement by MHC in triggering selection; the interaction of CD8 and CD4 with MHC class I and class II, respectively; is thought to be important in regulating the selection process. To study potential mechanisms involved in positive selection of CD8+ cells, we have analyzed mice expressing a unique transgenic TCR. The transgenic receptor recognizes the HY male Ag in the context of the MHC class I molecule, H2-D(b). We describe that CD8 and the TCR are selectively associated in thymocytes of mice expressing the restricting MHC, but not in thymocytes of mice expressing a nonrestricting MHC. pp56lck and pp59fyn, the tyrosine kinases associated with CD8 and TCR, respectively, were found to be present in this complex in an activated form. No comparable TCR-CD4 complex formation was found in thymuses undergoing positive selection to CD8+ cells. The formation of a multimolecular complex between CD8 and TCR, in which pp56lck and pp59fyn are activated, may initiate specific signaling programs involved in the maturation of CD8+ cells. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. JOHNS HOPKINS UNIV,SCH MED,DEPT MED ONCOL & MOLEC BIOL & GENET,BALTIMORE,MD 21205. RP CARRERA, AC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,M-854,44 BINNEY ST,BOSTON,MA 02115, USA. OI Carrera, Ana/0000-0002-3999-5434 FU NCI NIH HHS [CA43803] NR 54 TC 23 Z9 23 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 NOV 15 PY 1992 VL 149 IS 10 BP 3142 EP 3149 PG 8 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000003 PM 1431093 ER PT J AU SUGITA, K HIROSE, T ROTHSTEIN, DM DONAHUE, C SCHLOSSMAN, SF MORIMOTO, C AF SUGITA, K HIROSE, T ROTHSTEIN, DM DONAHUE, C SCHLOSSMAN, SF MORIMOTO, C TI CD27, A MEMBER OF THE NERVE GROWTH-FACTOR RECEPTOR FAMILY, IS PREFERENTIALLY EXPRESSED ON CD45RA+ CD4 T-CELL CLONES AND INVOLVED IN DISTINCT IMMUNOREGULATORY FUNCTIONS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; TUMOR-NECROSIS-FACTOR; HELPER-INDUCER; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODY; ACTIVATION ANTIGEN; PERIPHERAL-BLOOD; LYMPHOCYTES-T; SUBSETS; SUBPOPULATIONS AB CD27 is a disulfide-linked 120-kDa homodimer expressed on the majority of peripheral T cells at variable density that belongs to the recently defined nerve growth factor receptor family. mAb reactive with CD27 can either enhance or inhibit T cell activation, suggesting a crucial role in the process of T cell activation. We now show that CD27 is preferentially expressed on the CD45RA+CD45RO-CD29low subset of CD4 cells. CD27 expression on this subset is maintained for a prolonged period in culture after PHA activation. In contrast, CD45RA-CD45RO+-CD29high subset of CD4 cells express very low level of CD27, and its expression is lost within 2 wk after PHA activation. To further analyze the differential expression of CD27 on these reciprocal subsets of CD4 cells, we developed T cell clones by stimulating isolated CD4+CD45RA+ and CD4+CD45RO+ populations with PHA. T cell clones derived from cells originally CD45RA+ retained both CD45RA and CD27 expression, whereas T cell clones derived from cells originally CD45RO+ were CD45RA- and CD27-. In functional assays, IL-4 production could only be induced in CD45RA-CD27- CD4 clones by stimulation with PMA and ionomycin. Four of six CD45RA+ CD4 clones had suppressor activity in PWM-driven IgG synthesis, whereas five of six CD45RA- CD4 clones had helper activity. Of interest, the suppressor activity of CD45RA+CD27+ clones was partially blocked by pretreatment with anti-CD27 mAb (1A4). Anti-1A4 pretreatment of these T cell clones resulted in elevation of intracellular cAMP levels. Thus, CD27 appears to play a role in the function of CD45RA+CD27+ CD4 cells, and may be involved in suppressor activity of these cells at least in part via its effects on cAMP production. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NIAID NIH HHS [AI-29530, AI-12069]; NIAMS NIH HHS [AR-33713] NR 60 TC 65 Z9 65 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 NOV 15 PY 1992 VL 149 IS 10 BP 3208 EP 3216 PG 9 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000011 PM 1358967 ER PT J AU EPPERSON, DE ARNOLD, D SPIES, T CRESSWELL, P POBER, JS JOHNSON, DR AF EPPERSON, DE ARNOLD, D SPIES, T CRESSWELL, P POBER, JS JOHNSON, DR TI CYTOKINES INCREASE TRANSPORTER IN ANTIGEN PROCESSING-1 EXPRESSION MORE RAPIDLY THAN HLA CLASS-I EXPRESSION IN ENDOTHELIAL-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TUMOR-NECROSIS-FACTOR; TOXIC LYMPHOCYTES-T; HEAVY-CHAIN; B ANTIGENS; MHC; INVITRO; REGION; MOLECULES; PEPTIDES AB Transporter in Ag processing-1 (TAP- 1, previously called PSF-1 or Ring-4) is an MHC-encoded gene product that is required for efficient association of intracellular peptide Ag with nascent HLA class I H chain and beta2-microglobulin, thereby permitting assembly and normal surface expression of the class I molecules. TAP-1 is thought to function as a component of a transmembrane pump, that transports cytoplasmically-derived peptides into the lumen of the endoplasmic reticulum where class I molecules assemble. Synthesis and expression of HLA class I molecules is increased in human endothelial cells by IFN-beta, IFN-gamma, and TNF. We report these same cytokines increase TAP-1 expression. As with class I, TAP-1 is also synergistically increased by combinations of TNF with IFN. Interestingly, cytokine-induced increases in TAP-1 mRNA are markedly more rapid than increases in class I mRNA. This rapid increase in TAP-1 mRNA is reflected in a rapid increase in TAP-1 protein. These results demonstrate that TAP-1 synthesis and class I synthesis are regulated in parallel. The rapidity of the cytokine response of TAP-1 compared to class I further suggests that the constitutive level of TAP-1 expression in endothelial cells is not sufficient to support inducible increases in class I expression. C1 YALE UNIV,SCH MED,BOYER CTR MOLEC MED,295 CONGRESS AVE,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,HOWARD HUGHES MED INST,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,COMM IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. FU NCI NIH HHS [CA 09141]; NHLBI NIH HHS [HL36003] NR 32 TC 103 Z9 103 U1 4 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1992 VL 149 IS 10 BP 3297 EP 3301 PG 5 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000022 PM 1385520 ER PT J AU KOZIEL, MJ DUDLEY, D WONG, JT DIENSTAG, J HOUGHTON, M RALSTON, R WALKER, BD AF KOZIEL, MJ DUDLEY, D WONG, JT DIENSTAG, J HOUGHTON, M RALSTON, R WALKER, BD TI INTRAHEPATIC CYTOTOXIC LYMPHOCYTES-T SPECIFIC FOR HEPATITIS-C VIRUS IN PERSONS WITH CHRONIC HEPATITIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NON-B-HEPATITIS; CHRONIC LIVER-DISEASE; NON-A; NUCLEOCAPSID ANTIGEN; FINE SPECIFICITY; CELLS; RECOGNITION; ANTIBODIES; GENOME; PATHOGENESIS AB Hepatitis C virus (HCV) is a major cause of post-transfusion and sporadic hepatitis worldwide, leading to chronic liver disease in at least 50% of infected individuals. The pathogenic mechanisms that result in chronic hepatitis are unknown. Lymphocytes are typically observed within the hepatic parenchyma, but the functional characteristics of these cells have not been defined. In this study, liver-infiltrating lymphocytes from two subjects with chronic HCV hepatitis were cloned at limiting dilution and tested for HCV-specific cytolytic activity using autologous target cells infected with vaccinia viruses expressing recombinant HCV Ag or sensitized with synthetic HCV peptides. In both subjects, HCV-specific, HLA class I-restricted CTL were identified that recognized epitopes in variable regions of either the envelope or nonstructural proteins. These results demonstrate the presence of HCV-specific CTL at the site of tissue damage in persons with chronic HCV hepatitis, and provide a means to evaluate the possible pathogenic role of these cells in HCV infection. C1 MASSACHUSETTS GEN HOSP,DEPT MED,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,IMMUNOPATHOL & GASTROINTESTINAL UNIT,BOSTON,MA 02114. CHIRON CORP,EMERYVILLE,CA 94608. RI Ralston, Robert/A-6924-2009; Yang, Chen/G-1379-2010 FU NIAID NIH HHS [AI27050, AI31563] NR 46 TC 451 Z9 456 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 NOV 15 PY 1992 VL 149 IS 10 BP 3339 EP 3344 PG 6 WC Immunology SC Immunology GA JX480 UT WOS:A1992JX48000028 PM 1385523 ER PT J AU INOGUCHI, T BATTAN, R HANDLER, E SPORTSMAN, JR HEATH, W KING, GL AF INOGUCHI, T BATTAN, R HANDLER, E SPORTSMAN, JR HEATH, W KING, GL TI PREFERENTIAL ELEVATION OF PROTEIN-KINASE-C ISOFORM-BETA-II AND DIACYLGLYCEROL LEVELS IN THE AORTA AND HEART OF DIABETIC RATS - DIFFERENTIAL REVERSIBILITY TO GLYCEMIC CONTROL BY ISLET CELL TRANSPLANTATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VASCULAR SMOOTH-MUSCLE; PANCREATIC-ISLETS; ENDOTHELIAL-CELLS; 1,2-DIACYLGLYCEROL CONTENT; 2ND MESSENGERS; GLUCOSE; INSULIN; COMPLICATIONS; PHOSPHOLIPIDS; PATHOGENESIS AB In the present study, we have measured protein kinase C (PKC) specific activities and total diacylglycerol (DAG) level in the aorta and heart of rats, which showed that after 2 weeks of streptozotocin (STZ)-induced diabetes, membranous PKC specific activity and total DAG content were increased significantly by 88% and 40% in the aorta and by 21% and 72% in the heart, respectively. Hyperglycemia was identified as being a causal factor since elevated glucose levels increased DAG levels in cultured aortic endothelial and smooth muscle cells. Analysis by immunoblotting revealed that only a and betaII PKC isoenzymes are detected in these two tissues and vascular cells among those studied. In STZ-induced diabetic rats, betaII isoenzyme is preferentially increased in both aorta and heart, whereas PKC alpha did not change significantly. The increases in membranous PKC specific activity and DAG level are observed in both spontaneous diabetes-prone diabetic BB rats as well as in STZ-induced diabetic BB and Sprague-Dawley rats, which persisted for up to 5 weeks. After 2 weeks of diabetes without treatment, the normalization of blood glucose levels for up to 3 weeks with islet cell transplants in STZ-induced diabetic BB rats reversed the biochemical changes only in the heart, but not in the aorta. These results suggest that PKC activity and DAG level may be persistently activated in the macrovascular tissues from diabetic animals and indicate a possible role for these biochemical parameters in the development of diabetic chronic vascular complications. C1 BRIGHAM & WOMENS HOSP, DEPT MED, JOSLIN DIABET CTR, DIV RES, 1 JOSLIN PL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. UNIV MASSACHUSETTS, DEPT MED, WORCESTER, MA 01655 USA. FU NEI NIH HHS [EY05110]; PHS HHS [36836] NR 45 TC 604 Z9 617 U1 3 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 1992 VL 89 IS 22 BP 11059 EP 11063 DI 10.1073/pnas.89.22.11059 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JY874 UT WOS:A1992JY87400103 PM 1438315 ER PT J AU JOHNSON, RS SPIEGELMAN, BM PAPAIOANNOU, V AF JOHNSON, RS SPIEGELMAN, BM PAPAIOANNOU, V TI PLEIOTROPIC EFFECTS OF A NULL MUTATION IN THE C-FOS PROTOONCOGENE SO CELL LA English DT Article ID TRANSFORMED-CELL LINE; EMBRYONIC STEM-CELLS; ANTISENSE RNA; DNA-BINDING; GENE-EXPRESSION; TRANSGENIC MICE; GLUCOCORTICOID RECEPTOR; TARGETED DISRUPTION; MOLECULAR-CLONING; NERVOUS-SYSTEM AB The c-fos proto-oncogene has been implicated as a central regulatory component of the nuclear response to mitogens and other extracellular stimuli. Embryonic stem cells targeted at the c-fos locus have been used to generate chimeric mice that have transmitted the mutated allele through the germline. Homozygous mutants show reduced placental and fetal weights and significant loss of viability at birth. Approximately 40% of the homozygous mutants survive and grow at normal rates until severe osteopetrosis, characterized by foreshortening of the long bones, ossification of the marrow space, and absence of tooth eruption, begins to develop at approximately 11 days. Among other abnormalities, these mice show delayed or absent gametogenesis, lymphopenia, and altered behavior. Despite these defects, many live as long as their wild-type or heterozygous littermates (currently 7 months). These data indicate that c-fos is not required for the growth of most cell types but is involved in the development and function of several distinct tissues. C1 TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP JOHNSON, RS (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. OI Johnson, Randall/0000-0002-4084-6639 FU NICHD NIH HHS [HD24926, HD27295] NR 61 TC 529 Z9 531 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD NOV 13 PY 1992 VL 71 IS 4 BP 577 EP 586 DI 10.1016/0092-8674(92)90592-Z PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JY676 UT WOS:A1992JY67600006 PM 1423615 ER PT J AU GARRICK, T YANG, H TRAUNER, M LIVINGSTON, E TACHE, Y AF GARRICK, T YANG, H TRAUNER, M LIVINGSTON, E TACHE, Y TI THYROTROPIN-RELEASING-HORMONE ANALOG INJECTED INTO THE RAPHE-PALLIDUS AND RAPHE-OBSCURUS INCREASES GASTRIC CONTRACTILITY IN RATS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE RAPHE NUCLEI (MEDULLARY); VAGUS; ATROPINE; RX-77368; THYROTROPIN-RELEASING HORMONE ID DORSAL VAGAL COMPLEX; MEDULLARY RAPHE; TRH ANALOG; SOLITARY TRACT; MOTOR NUCLEUS; VAGUS NERVE; STIMULATION; ACID; PROJECTIONS; MOTILITY AB The present study was performed to investigate the influence of the chemical stimulation of medullary raphe nuclei by the stable TRH (thyrotropin-releasing hormone) analog, RX 77368, on gastric contractility. Urethane-anesthetized rats were acutely implanted with miniature strain gauge force transducers on the corpus of the stomach for continuous recording of gastric contractility. Traces were analyzed by computer. Microinjections of vehicle or RX 77368 into the raphe pallidus or raphe obscurus were performed using pressure injection of 50 nl through glass micropipettes 30 min following basal recording of gastric contractility. RX 77368 (0.7-77 pmol) dose dependently stimulated gastric contractility when microinjected into the raphe pallidus and raphe obscurus. The stimulation of gastric contractions induced by microinjection of RX 77368 (77 pmol) into these raphe nuclei was completely blocked by vagotomy and prevented (raphe obscurus) or reduced (raphe pallidus) by atropine. RX 77368 (7.7-77 pmol) microinjected into the inferior olive, pyramidal tract, medial lemiscus was ineffective. These results demonstrate that chemical stimulation of the raphe pallidus and obscurus by RX 77368 stimulates gastric contractility through vagal and muscarinic pathways. These data suggest a role for medullary raphe nuclei in the central vagal regulation of gastric contractility. C1 W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG & RES,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,BRAIN RES INST,DEPT PSYCHIAT,CTR ULCER RES & EDUC,LOS ANGELES,CA 90024. RP GARRICK, T (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT PSYCHIAT,W116A,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. FU NIDDK NIH HHS [DK-30110, DK-41301]; NIMH NIH HHS [MH-00663] NR 35 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 13 PY 1992 VL 223 IS 1 BP 75 EP 81 DI 10.1016/0014-2999(92)90820-T PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JY913 UT WOS:A1992JY91300011 PM 1478259 ER PT J AU ARNOLD, D DRISCOLL, J ANDROLEWICZ, M HUGHES, E CRESSWELL, P SPIES, T AF ARNOLD, D DRISCOLL, J ANDROLEWICZ, M HUGHES, E CRESSWELL, P SPIES, T TI PROTEASOME SUBUNITS ENCODED IN THE MHC ARE NOT GENERALLY REQUIRED FOR THE PROCESSING OF PEPTIDES BOUND BY MHC CLASS-I MOLECULES SO NATURE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; LINKED LMP; GENE; HLA; EXPRESSION; REGION; HEAVY; IDENTIFICATION; TRANSPORTER; DETERMINANT AB ANTIGEN processing provides major histocompatibility complex (MHC) class I molecules with short peptides, which they selectively bind and present to cytotoxic T lymphocytes1-4. The proteolytic system generating these peptides in the cytosol is unidentified, but their delivery into the endoplasmic reticulum is mediated by the TAP1-TAP2 transporter encoded in the MHC class II region5-9. Closely linked to TAP1 and TAP2 are genes for the LMP2 and LMP7 proteins10, which resemble components of proteasomes11-13, proteolytic complexes known to degrade cytosolic proteins14. This association has led to the common assumption that proteasomes function in this immunological pathway (discussed in ref. 15). We now show that the expression of stably assembled class I molecules and apparently normal peptide processing can be completely restored in the absence of LMP2 and LMP7 in the human lymphoblastoid cell line mutant 721.174 (refs 16, 17). The identity of LMP7 is directly confirmed by reconstitution of a proteasomal subunit after gene transfer. These results therefore dispute the hypothetical involvement of proteasomes in antigen processing, although a more subtle effect of LMP2 and LMP7 cannot be ruled out. C1 HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. YALE UNIV,SCH MED,HOWARD HUGHES MED INST,IMMUNOBIOL SECT,NEW HAVEN,CT 06510. RP ARNOLD, D (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 36 TC 215 Z9 215 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD NOV 12 PY 1992 VL 360 IS 6400 BP 171 EP 174 DI 10.1038/360171a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JX752 UT WOS:A1992JX75200064 PM 1436094 ER PT J AU SINGER, DE AF SINGER, DE TI RANDOMIZED TRIALS OF WARFARIN FOR ATRIAL-FIBRILLATION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material RP SINGER, DE (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 14 TC 42 Z9 42 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 NOV 12 PY 1992 VL 327 IS 20 BP 1451 EP 1453 DI 10.1056/NEJM199211123272009 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA JX479 UT WOS:A1992JX47900009 PM 1406862 ER PT J AU FRUH, K YANG, Y ARNOLD, D CHAMBERS, J WU, L WATERS, JB SPIES, T PETERSON, PA AF FRUH, K YANG, Y ARNOLD, D CHAMBERS, J WU, L WATERS, JB SPIES, T PETERSON, PA TI ALTERNATIVE EXON USAGE AND PROCESSING OF THE MAJOR HISTOCOMPATIBILITY COMPLEX-ENCODED PROTEASOME SUBUNITS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLASS-II REGION; MULTICATALYTIC PROTEINASE COMPLEXES; RAT HEPATOMA-CELLS; HUMAN MHC; MOLECULAR-CLONING; ESCHERICHIA-COLI; CDNA CLONING; TRANSMEMBRANE PROTEINS; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTOR AB The finding that two subunits of the proteasome, LMP2 and LMP7, are encoded in the major histocompatibility complex (MHC) has linked the proteasome which represents a major extralysosomal proteolytic system to the processing of intracellular antigens. Here we describe a second form of the human LMP7 cDNA, LMP7-E2, which has been identified during the characterization of novel genes in the MHC. The analysis of the genome organization of LMP7 revealed that LMP7-E1 and LMP7-E2 arise by alternative exon usage. Using specific antibodies against LMP2 and LMP7, we show that they are co-expressed with class I MHC molecules as well as a putative peptide transporter. The polypeptides encoded by LMP7 and LMP2 undergo proteolytic processing when incorporated into proteasomes, and the LMP7 precursor is derived mainly from LMP7-E2. Furthermore, our data suggest that LMP7 and LMP2 are mutually dependent for their incorporation into the proteasomal complex. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR VIROL, BOSTON, MA 02115 USA. RP FRUH, K (reprint author), SCRIPPS RES INST, LA JOLLA, CA 92037 USA. NR 55 TC 116 Z9 118 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 NOV 5 PY 1992 VL 267 IS 31 BP 22131 EP 22140 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW719 UT WOS:A1992JW71900025 PM 1429565 ER PT J AU FOLLI, F SAAD, MJA BACKER, JM KAHN, CR AF FOLLI, F SAAD, MJA BACKER, JM KAHN, CR TI INSULIN STIMULATION OF PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY AND ASSOCIATION WITH INSULIN-RECEPTOR SUBSTRATE-1 IN LIVER AND MUSCLE OF THE INTACT RAT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-I RECEPTOR; GROWTH FACTOR-I; DEPENDENT DIABETES-MELLITUS; KINASE-ACTIVITY; TYROSINE PHOSPHORYLATION; SKELETAL-MUSCLE; ENDOGENOUS SUBSTRATE; SIGNAL TRANSDUCTION; PDGF RECEPTOR; PROTEINS AB Growth factors stimulate the enzyme phosphatidylinositol (PI) 3-kinase in cells in culture. Insulin rapidly stimulates tyrosine phosphorylation of its endogenous substrate, insulin receptor substrate 1 (IRS-1), and in vitro IRS-1 associates with PI 3-kinase, thus activating the enzyme. We have examined whether insulin is capable of stimulating the PI 3-kinase pathway in two physiological target tissues for the actions of insulin in vivo, liver and skeletal muscle. After intraportal injection of insulin into anesthetized rats, there was a 2-fold stimulation of total hepatic PI 3-kinase activity in liver and muscle extracts and a 10- to 20-fold increase in PI 3-kinase activity immunoprecipitated with anti-IRS-1 antibodies. Stimulation of PI 3-kinase was accompanied by an association between this enzyme and IRS-1 as detected by immunoprecipitation of liver and muscle extracts with anti-IRS-1 antibodies and Western blotting with antibodies to the 85-kDa subunit of PI 3-kinase. Immunoprecipitation with anti-p85 antibodies and phosphotyrosine immunoblotting revealed no tyrosine phosphorylation of PI 3-kinase, but demonstrated co-precipitation of tyrosine-phosphorylated IRS-1, as well as another phosphotyrosine protein of approximately 135-140 kDa. Thus, IRS-1 phosphorylation plays a significant role in the activation of PI 3-kinase in vivo by insulin. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02215. RP FOLLI, F (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215, USA. OI folli, franco/0000-0001-9824-5222 FU NIDDK NIH HHS [DK 33201, DK 36836] NR 59 TC 227 Z9 232 U1 2 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 NOV 5 PY 1992 VL 267 IS 31 BP 22171 EP 22177 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW719 UT WOS:A1992JW71900030 PM 1385396 ER PT J AU RECNY, MA LUTHER, MA KNOPPERS, MH NEIDHARDT, EA KHANDEKAR, SS CONCINO, MF SCHIMKE, PA FRANCIS, MA MOEBIUS, U REINHOLD, BB REINHOLD, VN REINHERZ, EL AF RECNY, MA LUTHER, MA KNOPPERS, MH NEIDHARDT, EA KHANDEKAR, SS CONCINO, MF SCHIMKE, PA FRANCIS, MA MOEBIUS, U REINHOLD, BB REINHOLD, VN REINHERZ, EL TI N-GLYCOSYLATION IS REQUIRED FOR HUMAN CD2 IMMUNOADHESION FUNCTIONS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID T-CELL ACTIVATION; VESICULAR STOMATITIS-VIRUS; FUNCTION-ASSOCIATED ANTIGEN-3; SHEEP ERYTHROCYTE RECEPTOR; SURFACE-MOLECULE CD2; HUMAN LYMPHOCYTES-T; ALTERNATIVE PATHWAY; SIALYL-LEX; G-PROTEIN; 3 LFA-3 AB The T-lymphocyte glycoprotein receptor, CD2, mediates cell-cell adhesion by binding to the surface molecule CD58 (LFA-3) on many cell types including antigen presenting cells. Two domains comprise the CD2 extracellular segment, with all adhesion functions localized to the amino-terminal domain that contains a single N-glycosylation site at Asn65. We have defined an important role for the N-linked glycans attached to Asn65 of this domain in mediating CD2-CD58 interactions and also characterize its N-glycotype structure. Analysis of deglycosylated soluble recombinant CD2 as well as a mutant transmembrane CD2 molecule containing a single Asn65-Gln65 substitution demonstrates that neither deglycosylated CD2 nor the mutant CD2 transmembrane receptor binds CD58 or monoclonal antibodies directed at native CD2 adhesion domain epitopes. Electrospray ionization-mass spectrometry demonstrates that high mannose oligosaccharides ((Man)nGlcNAC2, n = 5-9) are the only N-glycotypes occupying Asn65 when soluble CD2 is expressed in Chinese hamster ovary cells. Based on a model of human CD2 secondary structure, we propose that N-glycosylation is required for stabilizing domain 1 in the human receptor. Thus, N-glycosylation is essential for human CD2 adhesion functions. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,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,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. RP RECNY, MA (reprint author), PROCEPT INC,CAMBRIDGE,MA 02139, USA. FU NIAID NIH HHS [AI21226]; NIGMS NIH HHS [R01GM45781] NR 56 TC 57 Z9 57 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 NOV 5 PY 1992 VL 267 IS 31 BP 22428 EP 22434 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW719 UT WOS:A1992JW71900069 PM 1385399 ER PT J AU SUN, XJ MIRALPEIX, M MYERS, MG GLASHEEN, EM BACKER, JM KAHN, CR WHITE, MF AF SUN, XJ MIRALPEIX, M MYERS, MG GLASHEEN, EM BACKER, JM KAHN, CR WHITE, MF TI EXPRESSION AND FUNCTION OF IRS-1 IN INSULIN SIGNAL TRANSMISSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE-ACTIVITY; GROWTH FACTOR-I; 3T3-L1 ADIPOCYTES; RECEPTOR; PHOSPHORYLATION; CELLS; SUBSTRATE; PROTEIN; TRANSDUCTION; SEQUENCE AB IRS-1 is a major insulin receptor substrate which may play an important role in insulin signal transmission. The mRNA for IRS-1 in rat cells and tissues is about 9.5 kilobases (kb). Rat liver IRS-1 was stably expressed in Chinese hamster ovary (CHO) cells (CHO/IRS-1). Although its calculated molecular mass is 131 kDa, IRS-1 from quiescent cells migrated between 165 and 170 kDa during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. IRS-1 was phosphorylated strongly on serine residues and weakly on threonine residues before insulin stimulation. Insulin immediately stimulated tyrosine phosphorylation of IRS-1, and after 10-30 min with insulin its apparent molecular mass increased to 175-180 kDa. Expression of the human insulin receptor and rat IRS-1 together in CHO/IR/IRS-1 cells increased the basal serine phosphorylation of IRS-1 and strongly increased tyrosine phosphorylation during insulin stimulation. Purified insulin receptors directly phosphorylated baculovirus-produced IRS-1 exclusively on tyrosine residues. By immunofluorescence, IRS-1 was absent from the nucleus, but otherwise distributed uniformly before and after insulin stimulation. Some IRS-1 associated with the insulin receptor during insulin stimulation. In addition, a phosphatidylinositol 3'-kinase associated with IRS-1 during insulin stimulation, and this association was more sensitive to insulin in CHO cells overexpressing the insulin receptor (CHO/IR cells), more responsive to insulin in CHO/IRS-1 cells, and both sensitive and responsive in CHO/IR/IRS-1 cells. Similarly, insulin-stimulated DNA synthesis was more sensitive to insulin in CHO/IR cells, and more responsive in CHO/IRS-1 cells; however, insulin-stimulated DNA synthesis was sensitive but poorly responsive to insulin in CHO/IR/IRS-1 cells. Together, these results suggest that IRS-1 is a direct physiologic substrate of the insulin receptor and may play an important role in insulin signal transmission. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM CELLULAR & DEV BIOL,BOSTON,MA 02115. RP SUN, XJ (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK 36836, DK33201, DK43808] NR 41 TC 269 Z9 272 U1 2 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 NOV 5 PY 1992 VL 267 IS 31 BP 22662 EP 22672 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW719 UT WOS:A1992JW71900103 PM 1385403 ER PT J AU SMALLEY, RV ANDERSEN, JW HAWKINS, MJ BHIDE, V OCONNELL, MJ OKEN, MM BORDEN, EC AF SMALLEY, RV ANDERSEN, JW HAWKINS, MJ BHIDE, V OCONNELL, MJ OKEN, MM BORDEN, EC TI INTERFERON ALFA COMBINED WITH CYTOTOXIC CHEMOTHERAPY FOR PATIENTS WITH NON-HODGKINS-LYMPHOMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN-LEUKOCYTE INTERFERON; COOPERATIVE-ONCOLOGY-GROUP; SINGLE-AGENT CHEMOTHERAPY; METASTATIC BREAST-CANCER; HAIRY-CELL LEUKEMIA; MALIGNANT-LYMPHOMA; MULTIPLE-MYELOMA; COMBINATION CHEMOTHERAPY; RECOMBINANT LEUKOCYTE AB Background. Interferon alfa has been found to be effective as an antitumor agent (with a response rate of 30 percent) in patients with low-grade non-Hodgkin's lymphoma, but its effectiveness in those with intermediate-grade non-Hodgkin's lymphoma has been less adequately tested. In a prospective randomized study we evaluated the effectiveness of adding interferon alfa to cytotoxic chemotherapy in patients with clinically aggressive, low-grade non-Hodgkin's lymphoma and certain histologic variants of intermediate-grade non-Hodgkin's lymphoma, not including diffuse histiocytic lymphoma. Methods. The patients were randomly assigned to a regimen of cyclophosphamide, vincristine, prednisone, and doxorubicin or to this regimen combined with recombinant interferon alfa. Treatment was administered every four weeks, for 8 to 10 cycles. Results. The two regimens produced comparable objective responses, but the regimen including interferon had a greater effect in prolonging the time to treatment failure (P<0.001) and the duration of complete response (P = 0.03). Interferon alfa also had a greater effect on overall survival (P = 0.014) when the results were adjusted for important covariates. Conclusions. Interferon alfa, when added to a four-drug doxorubicin-based chemotherapy regimen, is an effective antitumor agent in patients with clinically aggressive low-grade or intermediate-grade non-Hodgkin's lymphoma. C1 UNIV WISCONSIN,CTR CLIN CANC,MADISON,WI 53706. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR BIOSTAT,BOSTON,MA 02115. VIRGINIA PIPER CANC INST,MINNEAPOLIS,MN. GEORGETOWN UNIV,WASHINGTON,DC 20057. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. MED COLL WISCONSIN,MILWAUKEE,WI 53226. RP SMALLEY, RV (reprint author), SYNERTRON INC,575 SCI DR,MADISON,WI 53711, USA. FU NCI NIH HHS [CA-14548, CA-14958, CA-06594] NR 43 TC 172 Z9 171 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 NOV 5 PY 1992 VL 327 IS 19 BP 1336 EP 1341 DI 10.1056/NEJM199211053271902 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JW077 UT WOS:A1992JW07700002 PM 1406835 ER PT J AU GORDON, LI HARRINGTON, D ANDERSEN, J COLGAN, J GLICK, J NEIMAN, R MANN, R RESNICK, GD BARCOS, M GOTTLIEB, A OCONNELL, M AF GORDON, LI HARRINGTON, D ANDERSEN, J COLGAN, J GLICK, J NEIMAN, R MANN, R RESNICK, GD BARCOS, M GOTTLIEB, A OCONNELL, M TI COMPARISON OF A 2ND-GENERATION COMBINATION CHEMOTHERAPEUTIC REGIMEN (M-BACOD) WITH A STANDARD REGIMEN (CHOP) FOR ADVANCED DIFFUSE NON-HODGKINS-LYMPHOMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LARGE-CELL LYMPHOMA; DOSE INTENSITY; HISTIOCYTIC LYMPHOMA; INTERMEDIATE-GRADE; RANDOMIZED TRIAL; ONCOLOGY-GROUP; METHOTREXATE; SUPERIORITY; LEUCOVORIN; SURVIVAL AB Background. In 1984, the Eastern Cooperative Oncology Group began a randomized controlled clinical trial of patients with advanced (stage III or IV) diffuse mixed or diffuse large-cell lymphoma to determine whether complete-remission rates, survival, and toxicity differed when patients were treated with a chemotherapeutic regimen containing cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), as compared with a regimen containing bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone, methotrexate, and leucovorin (m-BACOD). Methods. From July 1984 through January 1988, 392 patients were enrolled, 325 of whom (83 percent) were eligible for the analysis and capable of being evaluated. The extent of disease was defined according to standard staging techniques, including bilateral bone-core biopsies in 88 percent of patients. Randomization was stratified according to age (<60 or greater-than-or-equal-to 60 years), performance status (0, 1, or other), stage (III or IV), and histologic presentation (diffuse mixed or diffuse large-cell lymphoma). Results. After a median follow-up of four years, there were no significant differences in rates of complete remission, time to treatment failure, disease-free survival, or overall survival in the patients treated with CHOP as compared with those treated with m-BACOD. However, there was more severe and life-threatening pulmonary, infectious, and hematologic toxicity associated with the m-BACOD regimen. In an attempt to measure the importance of dose intensity in the 325 patients who could be analyzed, we retrospectively calculated dose intensity (measured in milligrams per square meter of body-surface area per week) and normalized dose intensity (defined as a percentage of the prescribed dose) for all drugs. The median normalized dose intensity for both cyclophosphamide and doxorubicin was found to be greater in the patients treated with CHOP than in those treated with m-BACOD. Conclusions. For patients with stage III or IV diffuse mixed or diffuse large-cell lymphoma, CHOP is superior to m-BACOD, but the role of dose intensity is not yet clear. C1 ROBERT F LURIE CANC CTR,CHICAGO,IL. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. INDIANA UNIV,MED CTR,INDIANAPOLIS,IN 46204. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,BUFFALO,NY 14263. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY 10021. SUNY HOSP SYRACUSE,UPSTATE MED CTR,SYRACUSE,NY. RP GORDON, LI (reprint author), NORTHWESTERN UNIV,SCH MED,DEPT MED,DIV HEMATOL ONCOL,303 E CHICAGO AVE,CHICAGO,IL 60611, USA. OI Gordon, Leo/0000-0003-1666-7064 FU NCI NIH HHS [CA 13650, CA 17145, CA 23318] NR 31 TC 276 Z9 284 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 NOV 5 PY 1992 VL 327 IS 19 BP 1342 EP 1349 DI 10.1056/NEJM199211053271903 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA JW077 UT WOS:A1992JW07700003 PM 1383819 ER PT J AU HELLER, HM SOUTHERN, JF PALMER, EL LEE, J AF HELLER, HM SOUTHERN, JF PALMER, EL LEE, J TI A 60-YEAR-OLD MAN WITH HIV-INFECTION, PERSISTENT DIARRHEA, AND INTRACTABLE RESPIRATORY-FAILURE - LYMPHOCYTIC MYOCARDITIS, PATCHY, FOCAL, AND MILD, WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID IMMUNE-DEFICIENCY-SYNDROME; CARDIAC ABNORMALITIES; SYNDROME AIDS; CARDIOMYOPATHY; HEART; MANIFESTATIONS; DYSFUNCTION; ENTEROPATHY; PATIENT C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HELLER, HM (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 39 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 NOV 5 PY 1992 VL 327 IS 19 BP 1370 EP 1376 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA JW077 UT WOS:A1992JW07700008 ER PT J AU BRUINVELS, AT LANDWEHRMEYER, B MOSKOWITZ, MA HOYER, D AF BRUINVELS, AT LANDWEHRMEYER, B MOSKOWITZ, MA HOYER, D TI EVIDENCE FOR THE PRESENCE OF 5-HT(1B) RECEPTOR MESSENGER-RNA IN NEURONS OF THE RAT TRIGEMINAL GANGLIA SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Note DE TRIGEMINAL GANGLIA (RAT); 5-HT(1B) RECEPTOR MESSENGER RNA; 5-HT(1B) RECEPTOR BINDING SITES ID PLASMA AB In situ hybridization histochemistry and receptor autoradiography were used to determine the presence of 5-HT1B receptor messenger RNA (mRNA) and 5-HT1B receptor proteins, respectively, in rat trigeminal ganglia. Receptor autoradiography on rat trigeminal ganglia, using appropriate 5-HT1B radioligands, did not demonstrate any specific labelling. In contrast, in situ hybridization showed that many ganglion cells contain 5-HT1B receptor mRNA, suggesting the presence of presynaptic 5-HT1B receptors on trigeminovascular neurons. C1 SANDOZ PHARMA LTD,PRECLIN RES 360-604,CH-4002 BASEL,SWITZERLAND. KANTONSPITAL,DEPT NEUROPATHOL,CH-4002 BASEL,SWITZERLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STROKE RES LAB,BOSTON,MA 02114. OI Hoyer, Daniel/0000-0002-1405-7089 NR 8 TC 45 Z9 46 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD NOV 2 PY 1992 VL 227 IS 3 BP 357 EP 359 DI 10.1016/0922-4106(92)90017-P PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JV992 UT WOS:A1992JV99200017 PM 1473558 ER PT J AU ALROY, J SCHELLING, SH THALHAMMER, JG RAGHAVAN, SS NATOWICZ, MR PRENCE, EM ORGAD, U AF ALROY, J SCHELLING, SH THALHAMMER, JG RAGHAVAN, SS NATOWICZ, MR PRENCE, EM ORGAD, U TI ADULT ONSET LYSOSOMAL STORAGE DISEASE IN A TIBETAN TERRIER - CLINICAL, MORPHOLOGICAL AND BIOCHEMICAL-STUDIES SO ACTA NEUROPATHOLOGICA LA English DT Article DE ADULT CANINE LYSOSOMAL STORAGE DISEASE; MORPHOLOGY; BIOCHEMISTRY ID LECTIN HISTOCHEMISTRY; JAPANESE SPANIEL; GANGLIOSIDES AB We describe a novel late-onset lysosomal lipid storage disease affecting a Tibetan terrier. The principal clinical manifestations include visual loss, progressive cerebellar ataxia and dementia. A necropsy of an affected 10-year-old dog demonstrated cerebellar atrophy. Histological analysis revealed extensive loss of retinal ganglion cells and cerebellar Purkinje cells, and mild to moderate loss of neurons in the cerebrum, basal ganglia and spinal cord.There were generalized neuronal hypertrophy and multifocal neuronal necrosis associated with the presence of enlarged macrophages. Neurons and perineuronal macrophages contained cytoplasmic granules that stained with PAS, luxol fast blue and several lectins. The granules were sudanophilic and autofluorescent. Electron microscopic analysis revealed lysosomes laden with lamellated membrane structures in neurons, pancreatic ductal and centroacinar cells and in cultured fibroblasts. These findings indicate lysosomal storage of both lipid and carbohydrate. Biochemical analysis of brain lipids and numerous lysosomal enzyme assays of leukocytes and cultured fibroblasts were unsuccessful in elucidating the underlying enzyme defect, although a generalized increase of brain gangliosides was noted. C1 TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,DEPT MED,GRAFTON,MA. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV BIOMED SCI,WALTHAM,MA. EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,DIV MED GENET,WALTHAM,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. KIMRON VET INST,DEPT PATHOL,BET DAGAN,ISRAEL. RP ALROY, J (reprint author), TUFTS UNIV,SCH MED,DEPT PATHOL,136 HARRISON AVE,BOSTON,MA 02111, USA. NR 34 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD NOV PY 1992 VL 84 IS 6 BP 658 EP 663 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA JY197 UT WOS:A1992JY19700010 PM 1471473 ER PT J AU CHIAPPELLI, F TIO, D TRITT, SH PILATI, ML TAYLOR, AN AF CHIAPPELLI, F TIO, D TRITT, SH PILATI, ML TAYLOR, AN TI SELECTIVE EFFECTS OF FETAL ALCOHOL EXPOSURE ON RAT THYMOCYTE DEVELOPMENT SO ALCOHOL LA English DT Article DE FETAL ALCOHOL EXPOSURE; THYMOCYTE; MITOGEN PROLIFERATIVE RESPONSE; ANTI-CD3 STIMULATION; ACTIVATION MARKERS; GLUCOCORTICOID CYTOSOLIC RECEPTOR ID PROLIFERATIVE RESPONSE; ETHANOL INUTERO; CELLS AB The thymoproliferative response to concanavalin A (ConA) following fetal alcohol exposure (FAE) is higher than control (149%) on day 44, is lower than control (64%) by day 51, and normalizes by day 69 (88% of controls). The ontogeny of HLA-Dr and transferrin receptor (CD71) expression in response to anti-CD3 stimulation is similar among the groups, but is distinct from that of ConA proliferation. The ontogeny of glucocorticoid cytoplasmic receptor (GCCR) sites per thymocyte is also different from the ontogeny of the ConA response. The number of GCCR sites rises sharply (2.5-fold) in control rat thymocytes between days 30 and 44, and remains at that level at later time points. By contrast, the number of GCCR sites per FAE thymocytes rises nearly linearly and normalizes by day 72. Our data support the notion that prenatal alcohol exposure significantly alters thymic development and indicates that the relationship between the development of thymocyte functional responses and that of GCCR is more complex than initially hypothesized. C1 W LOS ANGELES VAMC, BRENTWOOD DIV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, PSYCHONEUROIMMUNOL PROGRAM, LOS ANGELES, CA 90024 USA. RP CHIAPPELLI, F (reprint author), UNIV CALIF LOS ANGELES, SCH MED, DEPT ANAT & CELL BIOL, BRAIN RES INST, LOS ANGELES, CA 90024 USA. FU NIAID NIH HHS [AI 07126] NR 14 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV-DEC PY 1992 VL 9 IS 6 BP 481 EP 487 DI 10.1016/0741-8329(92)90084-N PG 7 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA JZ040 UT WOS:A1992JZ04000006 PM 1472303 ER PT J AU OKADA, RD MURPHY, JH BOUCHER, CA POHOST, GM STRAUSS, HW JOHNSON, G DAGGETT, WM AF OKADA, RD MURPHY, JH BOUCHER, CA POHOST, GM STRAUSS, HW JOHNSON, G DAGGETT, WM TI RELATIONSHIP BETWEEN SEPTAL PERFUSION, VIABILITY, AND MOTION BEFORE AND AFTER CORONARY-ARTERY BYPASS-SURGERY SO AMERICAN HEART JOURNAL LA English DT Article ID VENTRICULAR VOLUME OVERLOAD; MYOCARDIAL-INFARCTION; WALL MOTION; ECHOCARDIOGRAPHY; DIMENSIONS; VARIANCE; SIZE; REST AB The etiology of abnormal interventricular septal motion occurring after open-heart surgery using cardiopulmonary bypass has not been clarified. Intraoperative ischemic septal injury has been proposed as one explanation for this finding. To examine this possibility, resting septal perfusion and viability were studied using rest and redistribution thallium-201 scintigraphy in 16 patients before and after coronary artery bypass surgery. The results were compared with septal motion on preoperative and postoperative resting gated blood pool scans. Preoperatively, septal thallium uptake was normal in 10 of 16 patients, and septal motion was normal in 14 of 16. Postoperatively, septal thallium uptake was normal in 11 of 16 patients, while septal motion was abnormal in all. Thus abnormal postoperative septal motion is usually associated with normal septal perfusion and viability on thallium scans and therefore is not the result of septal ischemic injury in a majority of patients. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,CARDIOVASC SURG UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT SURG,DIV NUCL MED,BOSTON,MA 02114. RP OKADA, RD (reprint author), UNIV OKLAHOMA,HLTH SCI CTR,WK WARREN MED RES INST,6465 S YALE,SUITE 1010,TULSA,OK 74136, USA. FU NHLBI NIH HHS [HL21751, HL26215, HL07416] NR 30 TC 17 Z9 19 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 NOV PY 1992 VL 124 IS 5 BP 1190 EP 1195 DI 10.1016/0002-8703(92)90399-G PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW458 UT WOS:A1992JW45800010 PM 1442485 ER PT J AU RIVERA, JM VANDERVOORT, PM THOREAU, DH LEVINE, RA WEYMAN, AE THOMAS, JD AF RIVERA, JM VANDERVOORT, PM THOREAU, DH LEVINE, RA WEYMAN, AE THOMAS, JD TI QUANTIFICATION OF MITRAL REGURGITATION WITH THE PROXIMAL FLOW CONVERGENCE METHOD - A CLINICAL-STUDY SO AMERICAN HEART JOURNAL LA English DT Article ID COLOR DOPPLER FLOW; VALVULAR REGURGITATION; ECHOCARDIOGRAPHY; INVITRO; ORIFICE; JETS; AREA; QUANTITATION; MOMENTUM; VOLUME AB Accurate quantitation of valvular incompetence remains an important goal in clinical cardiology. It has been shown previously that when color flow Doppler mapping is used, simple measurements of apparent jet size do not correlate closely with regurgitant flow rate and regurgitant fraction. Recently the proximal flow convergence method has been proposed to quantify valvular regurgitation by analysis of the converging flow field proximal to a regurgitant lesion. Flow rate Q can be calculated as Q = 2pir2v(a) where v(a) is the aliasing velocity at a distance r from the orifice. In 54 patients (43 with sinus rhythm and 11 with atrial fibrillation) who had at least mild mitral regurgitation according to semiquantitative assessment, regurgitant stroke volume, regurgitant flow rate, and regurgitant fraction were calculated with the proximal flow convergence method and compared with values that were obtained by the Doppler two-dimensional echocardiographic method. Regurgitant stroke volumes (V(r)) as calculated by the proximal flow convergence method correlated very closely with values that were obtained by the Doppler two-dimensional method, with r = 0.93 (y = 0.95x + 0.55) and DELTAV(r) = -0.3 +/- 4.0 cm3. Regurgitant flow rates (Q) as calculated by both methods showed a similar correlation: r = 0.93 (y = 0.95x + 54) and DELTAQ = -34 +/- 284 cm3/min. The correlation for regurgitant fraction (RF) as calculated by both techniques showed r = 0.89 (y = 0.98x + 0.006) and DELTARF = -0.005 +/- 0.06. All correlations were slightly better for the group of patients with sinus rhythm than for the study group of patients with atrial fibrillation. This study demonstrates that the proximal flow convergence method is an accurate and reproducible technique to quantify mitral regurgitation in patients with at least mild mitral regurgitation. This approach is easy and less time-consuming than the Doppler echocardiographic method. Although future refinements of this method are to be expected, flow calculations that are based on the assumption of simple hemispheric symmetry of the proximal flow field show excellent results and appear to be suitable for clinical application at present. C1 CLEVELAND CLIN FDN,DIV CARDIOL,DESK F15,9500 EUCLID AVE,CLEVELAND,OH 44195. MASSACHUSETTS GEN HOSP,NONINVAS CARDIAC LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RI rivera, miguel/D-5026-2014 NR 43 TC 80 Z9 80 U1 0 U2 2 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 NOV PY 1992 VL 124 IS 5 BP 1289 EP 1296 DI 10.1016/0002-8703(92)90414-Q PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW458 UT WOS:A1992JW45800025 PM 1442498 ER PT J AU THOMAS, JD FLACHSKAMPF, FA CHEN, CG GUERERRO, JL PICARD, MH LEVINE, RA WEYMAN, AE AF THOMAS, JD FLACHSKAMPF, FA CHEN, CG GUERERRO, JL PICARD, MH LEVINE, RA WEYMAN, AE TI ISOVOLUMIC RELAXATION-TIME VARIES PREDICTABLY WITH ITS TIME CONSTANT AND AORTIC AND LEFT ATRIAL PRESSURES - IMPLICATIONS FOR THE NONINVASIVE EVALUATION OF VENTRICULAR RELAXATION SO AMERICAN HEART JOURNAL LA English DT Article ID DIASTOLIC FUNCTION; DOPPLER ECHOCARDIOGRAPHY; HYPERTROPHIC CARDIOMYOPATHY; ANGINA-PECTORIS; DETERMINANTS; DYSFUNCTION; PHYSIOLOGY; ISCHEMIA; PRELOAD; PERIOD AB The isovolumic relaxation. time (IVRT) is an important noninvasive index of left ventricular diastolic function. Despite its widespread use, however, the IVRT has not been related analytically to invasive parameters of ventricular function. Establishing such a relationship would make the IVRT more useful by itself and perhaps allow it to be combined more precisely with other noninvasive parameters of ventricular filling. The purpose of this study was to validate such a quantitative relationship. Assuming isovolumic relaxation to be a monoexponential decay of ventricular pressure (p(v)) to a zero-pressure asymptote, it was postulated that the time interval from aortic valve closure (when p(v) = p(o)) until mitral valve opening (when p(v) = left atrial pressure, P(A)) would be given analytically by IVRT = tau[log(P(o)) - log(P(A))], where tau is the time constant of isovolumic relaxation and log is to the base e. To test this hypothesis we analyzed data from six canine experiments in which ventricular preload and afterload were controlled nonpharmacologically. In addition, tau was adjusted with the use of beta-adrenergic blockade and calcium infusion, as well as with hypothermis. In each experiment data were collected before and after the surgical formation of mitral stenosis, performed to permit the study of a wide range of left atrial pressures. High-fidelity left atrial, left ventricular, and aortic root pressures were digitized, the IVRT was measured from the aortic dicrotic notch until the left atrioventricular pressure crossover point, and tau was calculated by nonlinear least-squares regression. In 100 cardiac cycles analyzed, IVRT ranged from 21 to 150 msec, systolic blood pressure (p(s)) from 58 to 180 mm Hg, p(o) from 37 to 143 mm Hg, P(A) from 2.5 to 30.5 mm Hg, and tau from 19 to 100 msec. Significant univariate correlations were observed between IVRT and p(o) (r = 0.35), P(A) (r = -0.41), and tau (r = 0.45), as well as with the optimal multilinear combination of all three (r = 0.92). However, a better (p < 0.005) correlation was observed when P(o), P(A), and tau were combined in the proposed equation to yield a predicted IVRT (y) that closely approximated the measured IVRT (x): y = 1.09x + 7.6 (r = 0.97). A similarly good correlation was observed when systolic blood pressure was used in the expression instead of the aortic closing pressure: y = 1.01x + 23.9 (r = 0.96). As a secondary purpose of this study, the hemodynamic determinants of the early diastolic transmitral gradient were characterized. It was observed that the initial rate of growth in the atrioventricular pressure gradient (dDELTAp/dt, x) was almost perfectly correlated with the rate of the decrease in left ventricular pressure at mitral valve opening (-dp(v)/dt, y): y = 1.01x + 13.7 (r = 0.993, standard deviation from the regression line [SD reg] = 31.6 mm Hg/sec). Furthermore, -dp(v)/dt (x) was closely associated with the ratio of atrial pressure and tau (p(A)/tau): y = 1.11x + 32.8 (r = 0.90, SD reg = 96.5 mm Hg/sec). In conclusion, the IVRT has a predictable quantitative relationship to tau and to left atrial and aortic pressures. This observation has potential application to the noninvasive characterization of ventricular relaxation. C1 MASSACHUSETTS GEN HOSP,NONINVAS CARDIAC LAB,BOSTON,MA 02114. OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL38176] NR 44 TC 62 Z9 64 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 NOV PY 1992 VL 124 IS 5 BP 1305 EP 1313 DI 10.1016/0002-8703(92)90416-S PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW458 UT WOS:A1992JW45800027 PM 1442500 ER PT J AU CASALE, PN PALACIOS, IF ABASCAL, VM HARRELL, L DAVIDOFF, R WEYMAN, AE FIFER, MA AF CASALE, PN PALACIOS, IF ABASCAL, VM HARRELL, L DAVIDOFF, R WEYMAN, AE FIFER, MA TI EFFECTS OF DOBUTAMINE ON GORLIN AND CONTINUITY EQUATION VALVE AREAS AND VALVE RESISTANCE IN VALVULAR AORTIC-STENOSIS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DOPPLER ECHOCARDIOGRAPHY; ELDERLY PATIENTS; VALVULOPLASTY; FORMULA AB Previous studies demonstrated changes in aortic valve area calculated by the Gorlin equation under conditions of varying transvalvular flow in patients with valvular aortic stenosis (AS). To distinguish between flow-dependence of the Gorlin formula and changes in actual orifice area, the Gorlin valve area and 2 other measures of severity of AS, continuity equation valve area and valve resistance, were calculated under 2 flow conditions in 12 patients with AS. Transvalvular flow rate was varied by administration of dobutamine. During dobutamine infusion, right atrial and left ventricular end-diastolic pressures decreased, left ventricular peak systolic pressure and stroke volume increased, and systolic arterial pressure did not change. Heart rate increased by 19%, cardiac output by 38% and mean aortic valve gradient by 25%. The Gorlin valve area increased in all 12 patients by 0.03 to 0.30 cm2. The average Gorlin valve area increased from 0.67 +/- 0.05 to 0.79 0.06 cm2 (p <0.001). In contrast, the continuity equation valve area (calculated in a subset of 6 patients) and valve resistance did not change with dobutamine. The data support the conclusion that flow-dependence of the Gorlin aortic valve area, rather than an increase in actual orifice area, is responsible for the finding that greater valve areas are calculated at greater transvalvular flow rates. Valve resistance is a less flow-dependent means of assessing severity of AS. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,WACC 478,15 PARKMAN ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,CARDIAC UNIT,BOSTON,MA 02115. NR 19 TC 59 Z9 61 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 1992 VL 70 IS 13 BP 1175 EP 1179 DI 10.1016/0002-9149(92)90051-Y PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW285 UT WOS:A1992JW28500015 PM 1414942 ER PT J AU MCCABE, CJ WARREN, R AF MCCABE, CJ WARREN, R TI TRAUMA - AN ANNOTATED-BIBLIOGRAPHY OF THE RECENT LITERATURE SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Bibliography C1 MASSACHUSETTS GEN HOSP,DEPT EMERGENCY MED,FRUIT ST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 1992 VL 10 IS 6 BP 595 EP 610 DI 10.1016/0735-6757(92)90193-2 PG 16 WC Emergency Medicine SC Emergency Medicine GA JW136 UT WOS:A1992JW13600021 PM 1388393 ER PT J AU RAJENDRAN, SK REISER, JR BAUMAN, W ZHANG, RL GORDON, SK KORSTEN, MA AF RAJENDRAN, SK REISER, JR BAUMAN, W ZHANG, RL GORDON, SK KORSTEN, MA TI GASTROINTESTINAL TRANSIT AFTER SPINAL-CORD INJURY - EFFECT OF CISAPRIDE SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article AB Heartburn, bloating, and abdominal discomfort are common problems in patients with spinal cord injury but, despite its clinical significance, little is known about the gastrointestinal effects of spinal transections. To address the potential gastrointestinal pathophysiology of spinal cord injury, we measured mouth-to-cecum transit time (MCTT) in seven subjects with paraplegia and seven with quadriplegia. Gastric emptying was studied in six subjects with quadriplegia. MCTT was significantly prolonged in patients with quadriplegia, an abnormality corrected by the administration of cisapride. Patients with paraplegia, in contrast to those with quadriplegia, have normal mouth-to-cecum transit time. In addition, patients with quadriplegia had neither a prolonged gastric emptying time nor a change in gastric emptying time, with cisapride. Changes in gastrointestinal transit after spinal cord injury and the improvement of mouth-to-cecum transit time in subjects with quadriplegia, but not in those with paraplegia, may be explained by an imbalance between parasympathetic and sympathetic outflows to the gastrointestinal tract in this group of subjects. C1 BRONX VET ADM MED CTR,CTR ALCOHOL RES & TREATMENT,130 W KINGSBRIDGE RD,BRONX,NY 10468. BRONX VET ADM MED CTR,SPINAL CORD DAMAGE RES CTR,GASTROENTEROL SECT,BRONX,NY 10468. BRONX VET ADM MED CTR,SCI SERV,BRONX,NY 10468. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. NR 13 TC 49 Z9 49 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 1992 VL 87 IS 11 BP 1614 EP 1617 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JX319 UT WOS:A1992JX31900019 PM 1442685 ER PT J AU ALTHERR, MR GUSELLA, JF WASMUTH, JJ KUMMER, MA MCKERCHER, SW JOHNSON, VP AF ALTHERR, MR GUSELLA, JF WASMUTH, JJ KUMMER, MA MCKERCHER, SW JOHNSON, VP TI MOLECULAR-DETECTION OF A 4P-DELETION USING PCR-BASED POLYMORPHISMS - A TECHNIQUE FOR THE RAPID DETECTION OF THE WOLF-HIRSCHHORN SYNDROME SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE WOLF-HIRSCHHORN SYNDROME; 4P-DELETION; DNA DELETION MAPPING; PCR TYPING; SOUTHERN BLOT HYBRIDIZATION ID HUNTINGTON DISEASE GENE; DNA-SEQUENCE; SHORT ARM; LOCUS; CHROMOSOME-4; MARKERS; D4S125 AB Wolf-Hirschhorn syndrome (WHS) results from a deletion of part of chromosome 4p. The region of 4p consistently deleted in WHS is near the tip of 4p. Two loci in this region D4S95 and D4S125 are associated with highly informative VNTR polymorphisms and were recently converted to allow PCR-based screening. PCR analysis was used successfully to identify a small de novo deletion of 4p in a patient suspected of having WHS. This procedure allows a rapid and accurate confirmation of 4p deletions in cases where cytogenetics alone cannot provide a clear answer. C1 UNIV CALIF IRVINE,COLL MED,DEPT BIOL CHEM,IRVINE,CA 92717. MASSACHUSETTS GEN HOSP,CTR NEUROSCI,BOSTON,MA 02114. UNIV S DAKOTA,SCH MED,DEPT PEDIAT,DEPT OBSTET GYNECOL,CTR BIRTH DEFECTS GENET,VERMILLION,SD 57069. FU NHGRI NIH HHS [HG00169]; NINDS NIH HHS [NS16367, NS25631-04] NR 19 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 1 PY 1992 VL 44 IS 4 BP 449 EP 454 DI 10.1002/ajmg.1320440413 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA JV049 UT WOS:A1992JV04900012 PM 1442886 ER PT J AU RAUCH, SD BARTLEY, ML AF RAUCH, SD BARTLEY, ML TI ARGON-LASER STAPEDECTOMY - COMPARISON TO TRADITIONAL FENESTRATION TECHNIQUES SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article ID STAPEDOTOMY; OTOSCLEROSIS; SURGERY AB A retrospective review of all stapedectomies performed at the Massachusetts Eye and Ear Infirmary over a 13 month period was undertaken to compare the results of argon laser stapedectomy to conventional footplate fenestration techniques. Despite the fact that it was new and unfamiliar to the surgical staff, the complication rate was lower with the argon laser than with footplate fenestration by traditional pick or drill techniques. The incidence of footplate fracture or removal preventing use of a small fenestra technique was five times as likely to occur with traditional instruments as with the argon laser (p < 0.025). In revision stapedectomy sensorineural hearing loss was four times as likely to occur with traditional instruments as with the argon laser (p less-than-or-equal-to 0.05). The argon laser did not alter the operating time. Though not ideal for every case, the argon laser endo-oto-probe offers the surgeon a significant new tool to improve the outcome in stapes surgery. RP RAUCH, SD (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOL & LARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 18 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD NOV PY 1992 VL 13 IS 6 BP 556 EP 560 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA JX166 UT WOS:A1992JX16600014 PM 1449184 ER PT J AU PAPPOLLA, MA OMAR, RA SAMBAMURTI, K ANDERSON, JP ROBAKIS, NK AF PAPPOLLA, MA OMAR, RA SAMBAMURTI, K ANDERSON, JP ROBAKIS, NK TI THE GENESIS OF THE SENILE PLAQUE - FURTHER EVIDENCE IN SUPPORT OF ITS NEURONAL ORIGIN SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; IMAGE-ANALYSIS MICROSPECTROSCOPY; ALZHEIMERS-DISEASE; BETA-PROTEIN; PREAMYLOID DEPOSITS; TISSUE-SECTIONS; ANTIBODY; BRAINS; CDNA; LOCALIZATION AB Senile plaques are among the most conspicuous neuropathologic changes found in the brains of elderly individuals and patients with Alzheimer's disease (AD). The origin of the amyloid beta protein (AbetaP) that accumulates in senile plaques continues to be highly controversial. Recently, using quantitative immunohistochemistry and computerized image analysis, we obtained evidence that at least a subset of early ("diffuse") senile plaques originate from neurons. In the current investigation, we employed monoclonal antibodies to AbetaP and the same computerized methodology to examine in further detail the quantitative patterns of AbetaP deposition in diffuse plaques in a population of intellectually intact elderly individuals. The presence of neurocentric concentration gradients of AbetaP accumulation was confirmed in this study. Most significantly, this was the most predominant pattern of early amyloid deposition in the population studied The highest concentration of AbetaP was centered around neuronal cell bodies or their processes, and occasionally along neuronal plasma membranes. Computerized images showed patterns that can be interpreted as a pathogenetic sequence ranging from initial neurogenic concentration gradients centered around one single neuron to larger deposits (diffuse plaques) composed of several "anastomosing" gradients involving several adjacent neurons. It is proposed that the described very early deposits constitute the initial stage in the development of the senile plaque. Although this study does not fully prove that the accumulated AbetaP is synthesized in the neuron or neuronal process it surrounds, the images herein presented suggest that neurons are the initial nidus of plaque formation. C1 CUNY MT SINAI SCH MED,DEPT PATHOL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,FISHBERG RES CTR NEUROBIOL,NEW YORK,NY 10029. W VIRGINIA UNIV,DEPT PATHOL,MORGANTOWN,WV 26506. BRONX VET ADM MED CTR,BRONX,NY. RP PAPPOLLA, MA (reprint author), CUNY MT SINAI SCH MED,DEPT PSYCHIAT,BOX 1229,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. FU NIA NIH HHS [AG 05138, AG 08200] NR 34 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 1992 VL 141 IS 5 BP 1151 EP 1159 PG 9 WC Pathology SC Pathology GA JX306 UT WOS:A1992JX30600015 PM 1443049 ER PT J AU SCHUNKERT, H INGELFINGER, JR JACOB, H JACKSON, B BOUYOUNES, B DZAU, VJ AF SCHUNKERT, H INGELFINGER, JR JACOB, H JACKSON, B BOUYOUNES, B DZAU, VJ TI RECIPROCAL FEEDBACK-REGULATION OF KIDNEY ANGIOTENSINOGEN AND RENIN MESSENGER-RNA EXPRESSIONS BY ANGIOTENSIN-II SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE MESSENGER RIBONUCLEASE ID GLOMERULAR-FILTRATION RATE; CONVERTING ENZYME-INHIBITION; RENAL-FUNCTION; ADENYLATE-CYCLASE; RIBONUCLEIC-ACID; SODIUM-EXCRETION; GENE-EXPRESSION; HEART-FAILURE; RELEASE; PLASMA AB The present study asks whether angiotensin II (ANG II), a potent inhibitor of renal renin synthesis and release, regulates renal angiotensinogen synthesis. ANG II (or vehicle) was intravenously infused into male Sprague-Dawley rats for 3 days (vehicle or 100, 300, and 1,000 ng . kg-1 . min-1, n = 8/group), significantly increasing mean plasma ANG II concentrations and raising mean arterial blood pressure (MAP). ANG II dose dependently suppressed plasma renin concentration, kidney renin concentration, and renal renin mRNA levels. In contrast, ANG II infusion increased renal angiotensinogen mRNA levels stepwise to 122, 136 (P < 0.05), and 150% (P < 0.05) of control and also increased both liver mRNA levels (P < 0.05) and plasma angiotensinogen concentration (P < 0.05). Three days of angiotensin-converting enzyme inhibition (10 mg . kg-1 . day-I quinapril in drinking water, n = 8) significantly decreased MAP (P < 0.05) and increased both mean plasma renin concentration (P < 0.05) and renal renin mRNA levels (P < 0.005). Plasma ANG II concentration tended to decrease (not significant), and neither renal nor hepatic angiotensinogen mRNA levels displayed significant difference. However, when data from ANG II-infused and quinapril-treated rats were analyzed together, correlation between plasma ANG II concentrations and renal angiotensinogen mRNA levels was highly significant (P < 0.005, r = 0.585). Thus plasma ANG II upregulates renal angiotensinogen gene expression and downregulates renal renin gene expression, a reciprocal feedback regulation that may have important physiological consequences. C1 STANFORD UNIV,FALK CARDIOVASC RES CTR,300 PASTEUR DR,STANFORD,CA 94305. MASSACHUSETTS GEN HOSP,DIV PEDIAT NEPHROL,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-19259, HL-35252, HL-35792] NR 61 TC 108 Z9 108 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 NOV PY 1992 VL 263 IS 5 BP E863 EP E869 PN 1 PG 7 WC Physiology SC Physiology GA JZ778 UT WOS:A1992JZ77800032 PM 1443118 ER PT J AU ZHOU, WG CHAO, W LEVINE, BA OLSON, MS AF ZHOU, WG CHAO, W LEVINE, BA OLSON, MS TI ROLE OF PLATELET-ACTIVATING-FACTOR IN HEPATIC RESPONSES AFTER BILE-DUCT LIGATION IN RATS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE OBSTRUCTIVE JAUNDICE; ENDOGENOUS INFLAMMATION; KUPFFER CELLS; ENDOTOXIN ID ACETYLGLYCERYL ETHER PHOSPHORYLCHOLINE; URIC-ACID RELEASE; KUPFFER CELLS; OBSTRUCTIVE-JAUNDICE; LIVER; GLYCOGENOLYSIS; STIMULATION; METABOLISM; RECEPTORS; POTASSIUM AB Role of platelet-activating factor (PAF) as a potential mediator of hepatic pathophysiology was investigated using a rat model of obstructive jaundice. Over a 1-wk course of bile duct ligation, a sixfold increase in tissue levels of PAF (1.57 +/- 0.43 ng/g vs. control 0.24 + 0.08 ng/g) occurred in the liver, whereas no change was observed in PAF levels in plasma. Concomitantly, endotoxin was detected in portal blood drawn from jaundiced rats, and antagonism of the putative effect of endotoxin by neomycin plus polymyxin B reduced local PAF concentrations in livers from jaundiced animals. Induction of neutropenia failed to alter the elevated hepatic PAF concentrations. Moreover, a large quantity of PAF was released spontaneously from Kupffer cells isolated from livers derived from jaundiced rats but not from endothelial cells or hepatocytes from the same animals. An in vitro study using cultured Kupffer cells from normal rats indicated that Kupffer cells secreted a significant amount of PAF in response to lipopolysaccharide challenge; pretreatment of cells with polymyxin B prevented this stimulated PAF release. Treatment of animals with either of two PAF receptor antagonists (BN 52021 and WEB 2170) partially prevented the increase in tissue levels of eicosanoids and O2-derived free radicals and partially alleviated liver injury as judged by the appearance of glutamatepyruvate transaminase in the plasma of jaundiced rats. The present study indicates 1) that endogenous PAF may be an important signaling mediator for the hepatic inflammatory alterations associated with short-term bile duct ligation and 2) that the interaction of Kupffer cells with portal endotoxin is the mechanism by which PAF is produced locally. C1 UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT SURG,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NIDDK NIH HHS [DK-19473] NR 27 TC 39 Z9 39 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 NOV PY 1992 VL 263 IS 5 BP G587 EP G592 PN 1 PG 6 WC Physiology SC Physiology GA JZ778 UT WOS:A1992JZ77800053 PM 1443133 ER PT J AU MORIKAWA, E HUANG, Z MOSKOWITZ, MA AF MORIKAWA, E HUANG, Z MOSKOWITZ, MA TI L-ARGININE DECREASES INFARCT SIZE CAUSED BY MIDDLE CEREBRAL ARTERIAL-OCCLUSION IN SHR SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Note DE NITRIC OXIDE; FOCAL CEREBRAL ISCHEMIA; VASODILATION ID NITRIC-OXIDE; ENDOTHELIAL-CELLS; ISCHEMIA; RAT; HYPERTENSION; RELAXATION AB L-Arginine, but not D-arginine, serves as a precursor for the synthesis of nitric oxide (NO), a potent dilator of cerebral blood vessels. We examined the effects of administering L-arginine (300 mg/kg ip) on the volume of infarction in two models of focal cerebral ischemia in spontaneously hypertensive rats (SHR). L-Arginine was administered before (16 and 3 h) and after (5 min and 2 h) vessel occlusion, and animals were killed 24 h later. L-Arginine treatment decreased infarct size in rats subjected to distal middle cerebral arterial (MCA) plus ipsilateral common carotid arterial (CCA) occlusion by 31% [147 +/- 12 (saline) vs. 101 +/- 9 mm3 (L-arginine), P < 0.05]. D-Arginine, administered according to the same dosage and protocol, was without effect. In the group subjected to proximal MCA occlusion, L-arginine decreased infarction size in the striatum by 28% [47 +/- 5 (saline) vs. 34 +/- 3 mm3 (L-arginine), P < 0.05] and neocortex by 11% [193 +/- 7 (saline) vs. 171 +/- 8 mm3 (L-arginine), P < 0.05]. Changes in blood pressure or other measured physiological parameters did not account for the observed differences. The possible use of L-arginine for the treatment of focal cerebral ischemia merits further investigation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSURG & NEUROL SERV,STROKE RES LAB,32 FRUIT ST,BOSTON,MA 02114. FU NINDS NIH HHS [NS-10828] NR 27 TC 159 Z9 160 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 NOV PY 1992 VL 263 IS 5 BP H1632 EP H1635 PN 2 PG 4 WC Physiology SC Physiology GA JZ779 UT WOS:A1992JZ77900041 PM 1443214 ER PT J AU NELSON, CW WEI, EP POVLISHOCK, JT KONTOS, HA MOSKOWITZ, MA AF NELSON, CW WEI, EP POVLISHOCK, JT KONTOS, HA MOSKOWITZ, MA TI OXYGEN RADICALS IN CEREBRAL-ISCHEMIA SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CEREBRAL MICROCIRCULATION; HYDROXYL RADICAL; BLOOD-BRAIN BARRIER; ENDOTHELIUM-DEPENDENT VASODILATION ID SUPEROXIDE ANION; ARTERIOLAR DILATION; XANTHINE-OXIDASE; RELAXING FACTOR; BRAIN INJURY; ACETYLCHOLINE; HYPERTENSION; GENERATION; MECHANISMS; RAT AB Superoxide production was measured as the superoxide dismutase (SOD)-inhibitable portion of nitro blue tetrazolium (NBT) reduction after cerebral ischemia-reperfusion in anesthetized cats equipped with cranial windows. Significant superoxide production was found in the early reperfusion period and continued for more than 1 h after ischemia. Superoxide was not detected in control animals not subjected to ischemia, during ischemia, and at 120 min of reperfusion. After ischemia, the vasoconstrictor response to arterial hypocapnia was reduced. This effect was prevented by pretreatment with SOD plus catalase or by deferoxamine. The response to topical acetylcholine was converted to vasoconstriction after ischemia. The normal vasodilator response reappeared spontaneously at 120 min of reperfusion. The vasodilator response to acetylcholine was preserved in animals pretreated with SOD plus catalase. Blood-brain barrier permeability to labeled albumin and horseradish peroxidase was increased after ischemia. These effects were minimized by pretreatment with SOD and catalase. We conclude that superoxide generation occurs during reperfusion after cerebral ischemia for a fairly long period and that superoxide and its derivatives are responsible at least in part for the vasodilation and the abnormal reactivity as well as for the increase in blood-brain barrier permeability to macromolecules seen after ischemia. Furthermore, the findings suggest that the agent responsible for the vascular abnormalities is hydroxyl radical generated via the iron-catalyzed Haber-Weiss reaction. C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,BOX 662,MCV STN,RICHMOND,VA 23298. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSURG SERV,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02114. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT ANAT,RICHMOND,VA 23298. RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [HL-21851]; NINDS NIH HHS [NS-19316, NS-26361] NR 23 TC 224 Z9 226 U1 1 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 NOV PY 1992 VL 263 IS 5 BP H1356 EP H1362 PN 2 PG 7 WC Physiology SC Physiology GA JZ779 UT WOS:A1992JZ77900004 PM 1332509 ER PT J AU BLACKER, D TSUANG, MT AF BLACKER, D TSUANG, MT TI CONTESTED BOUNDARIES OF BIPOLAR DISORDER AND THE LIMITS OF CATEGORICAL DIAGNOSIS IN PSYCHIATRY SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 144TH ANNUAL MEETING OF THE AMERICAN PSYCHIATRIC ASSOC CY MAY 11-16, 1991 CL NEW ORLEANS, LA SP AMER PSYCHIAT ASSOC ID BORDERLINE PERSONALITY-DISORDER; DEFICIT HYPERACTIVITY DISORDER; MANIC-DEPRESSIVE ILLNESS; DSM-III; SCHIZOAFFECTIVE DISORDER; UNIPOLAR DEPRESSION; PSYCHOTIC DISORDERS; CONTROLLED FAMILY; MAJOR DEPRESSION; FOLLOW-UP AB The authors' primary objective is to outline the phenomenology, importance, and available data on issues concerning the boundaries between bipolar disorder and diagnoses such as schizophrenia, unipolar depression, and personality disorders. In addition, by illuminating the many difficulties with the boundaries of one of psychiatry's more robust diagnoses, they hope to awaken in the reader a healthy skepticism about current psychiatric nosology. For a topic of this scope, a literature review must be selective. For each boundary area, a mixture of classic and recent papers covering a range of validating criteria is included whenever possible. Good summary data are cited when available, as are a selection of relevant theoretical papers. The review indicates that current diagnostic criteria for bipolar disorder are generally reasonable, but there are many problem areas, most of which cannot be solved by changes in criteria. Notable among these are 1) the possibility of future manic episodes in unipolar disorder, 2) schizoaffective disorder, bipolar type, and 3) borderline personality disorder with prominent mood swings. The disputes concerning the boundaries of bipolar disorder illustrate the limitations of categorical diagnosis which result from the implementation of diagnostic criteria, the criteria themselves, the fundamental nosologic process, and the phenomena themselves. If these limitations are to be extended, it may be necessary to explore alternative ways of defining psychiatric diagnoses for different settings in research and clinical practice. C1 HARVARD UNIV,SCH PUBL HLTH,PROGRAM PSYCHIAT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. VET ADM MED CTR,BROCKTON,MA 02401. RP BLACKER, D (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,MGH E,9TH FLOOR,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH-17119, MH-43518, MH-46318] NR 88 TC 88 Z9 89 U1 5 U2 7 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1992 VL 149 IS 11 BP 1473 EP 1483 PG 11 WC Psychiatry SC Psychiatry GA JV476 UT WOS:A1992JV47600003 PM 1415815 ER PT J AU RENSHAW, PF GUIMARAES, AR FAVA, M ROSENBAUM, JF PEARLMAN, JD FLOOD, JG PUOPOLO, PR CLANCY, K GONZALEZ, RG AF RENSHAW, PF GUIMARAES, AR FAVA, M ROSENBAUM, JF PEARLMAN, JD FLOOD, JG PUOPOLO, PR CLANCY, K GONZALEZ, RG TI ACCUMULATION OF FLUOXETINE AND NORFLUOXETINE IN HUMAN BRAIN DURING THERAPEUTIC ADMINISTRATION SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; PSYCHIATRY; RAT AB In vivo fluorine-19 nuclear magnetic resonance spectroscopy was used to measure the brain concentration of fluoxetine and norfluoxetine in five patients with obsessive-compulsive disorder and three with major depression. The mean brain:plasma ratio of the parent drug plus the metabolite was significantly elevated to 2.6 (SD=1.0) (95% confidence interval=1.9-3.3). This accumulation may have implications for understanding both the therapeutic and the toxic effects of fluoxetine. C1 MASSACHUSETTS GEN HOSP,CTR NMR,BOSTON,MA. MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHEM LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ACUTE PSYCHIAT SERV,BOSTON,MA 02114. RP RENSHAW, PF (reprint author), MCLEAN HOSP,CTR BRAIN IMAGING,BELMONT,MA 02178, USA. NR 10 TC 67 Z9 67 U1 1 U2 4 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 NOV PY 1992 VL 149 IS 11 BP 1592 EP 1594 PG 3 WC Psychiatry SC Psychiatry GA JV476 UT WOS:A1992JV47600023 PM 1415832 ER PT J AU CHEW, FS ZAMBUTO, DA AF CHEW, FS ZAMBUTO, DA TI MECKELS-DIVERTICULUM SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP CHEW, FS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 10 Z9 10 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1992 VL 159 IS 5 BP 982 EP 982 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JU750 UT WOS:A1992JU75000012 PM 1414811 ER PT J AU GIRARD, MJ SAINI, S MUELLER, PR FLOTTE, TJ STARITZ, M DOMANKEVITZ, Y FERRUCCI, JT NISHIOKA, N AF GIRARD, MJ SAINI, S MUELLER, PR FLOTTE, TJ STARITZ, M DOMANKEVITZ, Y FERRUCCI, JT NISHIOKA, N TI PERCUTANEOUS OBLITERATION OF THE CYSTIC DUCT WITH A HOLMIUM - YTTRIUM-ALUMINUM-GARNET LASER - RESULTS OF INVITRO AND ANIMAL-EXPERIMENTS SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SHOCK-WAVE LITHOTRIPSY; TERT-BUTYL ETHER; TRANSCATHETER SCLEROSIS; GALLSTONE DISSOLUTION; GALLBLADDER; CHOLECYSTOSTOMY; CHOLECYSTOLITHOTOMY; FRAGMENTATION; OCCLUSION; ABLATION AB OBJECTIVE. The purpose of this study was to investigate the feasibility of using a holmium:yttrium-aluminum-garnet laser to permanently occlude the cystic duct in order to isolate the gallbladder from the biliary-enteric circulation and prevent gallstone formation. MATERIALS AND METHODS. To determine the optimal laser parameters (power and pulsing rate) for cystic duct thermocoagulation, 20 freshly excised porcine gallbladders with intact cystic ducts underwent low-energy (0.075-0.085 J/pulse) or high-energy (0.20-0.25 J/pulse) thermocoagulation. Histopathologic examination was done to determine the extent of cystic duct injury. After in vitro experiments, percutaneous transcholecystic laser thermocoagulation of the cystic duct was performed on 23 anesthetized domestic pigs (four controls). Cholangiograms immediately after laser thermocoagulation were obtained to assess cystic duct occlusion. Animals were sacrificed for histopathologic correlation immediately after laser thermocoagulation (n = 4), 72 hr later (n = 4), and 6 weeks later (n = 15). RESULTS. In the in vitro studies, all 10 cystic ducts in the high-energy group were occluded, while only four in the low-energy group were occluded. At histology, all cases in both groups showed circumferential injury to the cystic duct wall without injury to the cystic artery or vein. In the in vitro experiments, the cystic duct was successfully cannulated in 21 (91%) of 23 animals. Cholangiography after thermocoagulation showed occlusion of the cystic duct in 16 (84%) of 19 cases. Immediately after laser thermocoagulation, the cystic duct mucosa was circumferentially destroyed, whereas after 72 hr necrosis of the cystic duct wall and periductal tissues had occurred. By 6 weeks, all pigs had complete cystic duct fibrosis without injury to the common bile duct. CONCLUSION. Holmium:yttrium-aluminum-garnet laser thermocoagulation of the cystic duct can be performed easily, results in immediate cystic duct occlusion, and leads to permanent fibrous ductal obliteration by 6 weeks. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. NR 26 TC 5 Z9 5 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 NOV PY 1992 VL 159 IS 5 BP 991 EP 995 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JU750 UT WOS:A1992JU75000014 PM 1414812 ER PT J AU GIRARD, MJ SAINI, S MUELLER, PR LEE, MJ RIBEIRO, RE FERRUCCI, JT FLOTTE, TJ AF GIRARD, MJ SAINI, S MUELLER, PR LEE, MJ RIBEIRO, RE FERRUCCI, JT FLOTTE, TJ TI PERCUTANEOUS CHEMICAL GALLBLADDER SCLEROSIS AFTER LASER-INDUCED CYSTIC DUCT OBLITERATION - RESULTS IN AN EXPERIMENTAL-MODEL SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SHOCK-WAVE LITHOTRIPSY; TERT-BUTYL ETHER; TRANSCATHETER SCLEROSIS; GALLSTONE DISSOLUTION; ABLATION; CHOLECYSTECTOMY; OCCLUSION; RABBIT AB OBJECTIVE. Chemical gallbladder sclerosis has been attempted as a way to defunctionalize the gallbladder in patients who have undergone nonsurgical removal of gallstones and who are unable to undergo surgical/laparoscopic cholecystectomy. The purpose of this investigation was threefold: to study an animal model for chemical sclerosis of the gallbladder with 95% ethanol and 3% sodium tetradecyl sulfate, to attempt chemical sclerosis immediately after percutaneous cystic duct obliteration by laser thermocoagulation, and to assess histopathologic changes in the gallbladder after sclerosis. MATERIALS AND METHODS. Percutaneous cholecystostomy and laser thermocoagulation of the cystic duct was performed in 13 pigs. Eight pigs underwent immediate gallbladder sclerosis with 95% ethanol and 3% sodium tetradecyl sulfate while two pigs received 95% ethanol only. The remaining three pigs served as controls. The cholecystostomy catheter was removed immediately after the procedure. All animals were sacrificed 6 weeks after laser thermocoagulation. Multiple sections through the gallbladder, which included the adjacent liver, the cystic duct, and the common bile duct, were obtained for histologic examination. RESULTS. At autopsy, the gallbladder in all 10 animals who underwent gallbladder sclerosis was reduced in size compared with controls. In all treated animals, the gallbladder mucosa was denuded; however, in nine of 10 cases reepithelialization had occurred. Complete sclerosis without reepithelialization was achieved in one pig who received both ethanol and sodium tetradecyl sulfate. In the two animals who received ethanol only, the depth of wall necrosis around the gallbladder lumen was less than in those pigs who received both ethanol and sodium tetradecyl sulfate. No pigs showed signs of hepatic necrosis or injury to the common bile duct. CONCLUSION. Cystic duct laser thermocoagulation allows immediate gallbladder sclerotherapy without injury to the common bile duct. Sclerosis with ethanol and sodium tetradecyl sulfate results in denudation of the gallbladder mucosa. However, a single therapeutic session with immediate removal of the cholecystostomy catheter was inadequate for gallbladder ablation in this model because of reepithelialization. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114. NR 28 TC 9 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 NOV PY 1992 VL 159 IS 5 BP 997 EP 999 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JU750 UT WOS:A1992JU75000016 PM 1414814 ER PT J AU LEE, MJ HAHN, PF SAINI, S MUELLER, PR AF LEE, MJ HAHN, PF SAINI, S MUELLER, PR TI DIFFERENTIAL-DIAGNOSIS OF HYPERINTENSE LIVER-LESIONS ON T1-WEIGHTED MR IMAGES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP LEE, MJ (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 4 TC 14 Z9 14 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1992 VL 159 IS 5 BP 1017 EP 1020 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JU750 UT WOS:A1992JU75000020 PM 1329456 ER PT J AU THRALL, JH AF THRALL, JH TI CAPITAL PLANNING IN RADIOLOGY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article RP THRALL, JH (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,55 FRUIT ST,BOSTON,MA 02114, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 1992 VL 159 IS 5 BP 1107 EP 1111 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JU750 UT WOS:A1992JU75000042 PM 1414785 ER PT J AU NIELSEN, JL PAGE, CP MANN, C SCHWESINGER, WH FOUNTAIN, RL GROVER, FL AF NIELSEN, JL PAGE, CP MANN, C SCHWESINGER, WH FOUNTAIN, RL GROVER, FL TI RISK OF MAJOR ELECTIVE OPERATION AFTER MYOCARDIAL REVASCULARIZATION SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 44TH ANNUAL MEETING OF THE SOUTHWESTERN SURGICAL CONGRESS CY APR 26-29, 1992 CL SCOTTSDALE, AZ ID CORONARY-ARTERY BYPASS; SURGERY; DISEASE AB Although an increased surgical risk of ischemic myocardial disease is widely accepted, amelioration of this risk after coronary artery bypass is poorly defined. We compared the outcomes of major elective general and peripheral vascular operations in 181 patients with prior coronary artery bypass grafting (CABG) with outcomes in an age-, gender-, and procedure-matched group without prior CABG (NOCABG). Despite the perception of a greater operative risk in the CABG patients (more CABG patients in American Society of Anesthesiologists [ASA] class III and fewer in ASA class I, p <0.001), mortality (1.1% CABG versus 2.8% NOCABG) and morbidity (18.8% CABG versus 18.5% NOCABG) rates in the two groups were not significantly different. For patients who have undergone successful CABG, it appears that: (1) the risk of subsequent elective major general and vascular surgical operations is similar to that of an age-, gender-, and procedure-matched cohort, and (2) the mortality rate after elective operations is low. C1 AUDIE L MURPHY MEM VET ADM MED CTR,112G,7400 MERTON MINTER,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT SURG,SAN ANTONIO,TX 78284. PORTLAND STATE UNIV,PORTLAND,OR 97207. NR 6 TC 25 Z9 26 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 NOV PY 1992 VL 164 IS 5 BP 423 EP 426 DI 10.1016/S0002-9610(05)81173-0 PG 4 WC Surgery SC Surgery GA JY007 UT WOS:A1992JY00700004 PM 1443365 ER PT J AU QUINTANILLAMARTINEZ, L ZUKERBERG, LR HARRIS, NL AF QUINTANILLAMARTINEZ, L ZUKERBERG, LR HARRIS, NL TI PRETHYMIC ADULT LYMPHOBLASTIC LYMPHOMA - A CLINICOPATHOLOGICAL AND IMMUNOHISTOCHEMICAL ANALYSIS SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE LYMPHOMA; PRETHYMIC LYMPHOBLASTIC LYMPHOMA; LYMPH NODE; LANGERHANS CELL HISTIOCYTOSIS; LYMPHOBLASTIC LYMPHOMA ID NON-HODGKINS-LYMPHOMA; LANGERHANS CELL GRANULOMATOSIS; MALIGNANT T-CELLS; HISTIOCYTOSIS-X; EOSINOPHILIC GRANULOMA; LEUKEMIA; PHENOTYPE; DIFFERENTIATION; EXPRESSION; PATIENT AB The clinical, histologic, and immunohistologic features of three cases of pre-T-cell (CD7+/CD2-) lymphoblastic lymphoma in adults are reported. The patients were adults over age 50 years who had a relatively indolent nodal disease, partial involvement of lymph nodes, and primitive immunophenotype. The phenotype of the three cases was TdT+, HLA-DR+, CD34+, CD71+, CD38+, and CD7+, most resembling the normal prothymocyte, and in contrast to normal thymocytes, which generally coexpress CD1+, CD4+, and CD8+. The prethymic T-cell character was further supported by germline T-cell receptor beta and gamma chain genes. In contrast to most reported cases with this early immunophenotype, these patients had nodal disease but no peripheral blood involvement. Two of the three cases were associated with Langerhans' cell histiocytosis (histiocytosis X), a previously unreported association. Because of the Langerhans' cell histiocytosis and the relatively indolent clinical presentation, the differential diagnosis in all cases included both a benign process and a lower-grade lymphoma. Recognition of this unusual form of adult lymphoblastic lymphoma is essential for correct diagnosis and treatment. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,FRUIT ST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 33 TC 14 Z9 17 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 1992 VL 16 IS 11 BP 1075 EP 1084 DI 10.1097/00000478-199211000-00006 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA JU809 UT WOS:A1992JU80900006 PM 1471728 ER PT J AU YOUNG, RH SCULLY, RE AF YOUNG, RH SCULLY, RE TI UTERINE CARCINOMAS SIMULATING MICROGLANDULAR HYPERPLASIA - A REPORT OF 6 CASES SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE UTERUS; CARCINOMA; ENDOMETRIUM; CERVIX; MICROGLANDULAR HYPERPLASIA ID CLINICOPATHOLOGIC ANALYSIS; MUCINOUS ADENOCARCINOMA; PAPILLARY CYSTADENOMAS; BORDERLINE MALIGNANCY; CERVIX; ENDOMETRIUM; ENDOCERVIX AB Six uterine adenocarcinomas, one cervical and five endometrial, that simulated microglandular hyperplasia histologically are described. The cervical neoplasm occurred in a 34-year-old woman who had been taking oral contraceptives. The five endometrial cancers occurred in post-menopausal patients 57 to 69 years of age; two of them were receiving, or had been receiving, premarin and provera and two were receiving only premarin. The patient with the cervical neoplasm had an abnormality observed on pelvic examination. The five postmenopausal patients presented because of vaginal spotting, bleeding, or discharge; their carcinomas were discovered in endometrial curettage specimens. On initial pathologic examination two specimens were misinterpreted as benign and in the remaining four cases there was uncertainty as to whether the lesion was benign or malignant. All the neoplasms had conspicuous microglandular patterns, with the gland lumens typically containing eosinophilic mucinous secretion and numerous acute inflammatory cells, which were also characteristically prominent in the stroma. Subsequent hysterectomies in all the cases showed residual adenocarcinoma with more typical features. Three of the endometrial tumors were mucinous adenocarcinomas and two mixed mucinous and endometrioid adenocarcinomas; the cervical tumor was a moderately differentiated adenocarcinoma of endocervical type. These cases illustrate that microglandular hyperplasia should be diagnosed with caution in a post-menopausal patient, particularly if lesional tissue is present in an endometrial curettage specimen, and, rarely, cervical adenocarcinomas have foci that simulate microglandular hyperplasia. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP YOUNG, RH (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 20 TC 47 Z9 51 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 1992 VL 16 IS 11 BP 1092 EP 1097 DI 10.1097/00000478-199211000-00008 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA JU809 UT WOS:A1992JU80900008 PM 1471729 ER PT J AU MORRIS, EA WILCON, S TREADWELL, BV AF MORRIS, EA WILCON, S TREADWELL, BV TI INHIBITION OF INTERLEUKIN 1-MEDIATED PROTEOGLYCAN DEGRADATION IN BOVINE ARTICULAR-CARTILAGE EXPLANTS BY ADDITION OF SODIUM HYALURONATE SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID OSTEO-ARTHRITIS; FACTOR-BETA; NEUTRAL PROTEASE; JOINT EFFUSIONS; CHONDROCYTES; COLLAGENASE; ACTIVATION; METABOLISM; SECRETION; HORSE AB The effect of exogenous hyaluronate on normal cartilage metabolism and interleukin-1 (IL-1)-induced cartilage matrix degradation was investigated in a bovine cartilage explant culture system. Addition of hyaluronate at a concentration of 1.5 mg/ml to cartilage culture explants consistently decreased normal proteoglycan release from the matrix to a value less than that found in control cultures. Addition of 1.5 mg of hyaluronate/ml to IL-1 stimulated cartilage culture systems reduced proteoglycan release from the matrix by 83 to 113%. The reduction in control and IL-1-stimulated proteoglycan degradation by hyaluronate had a concentration-dependent trend. Evaluation of alterations in protein (enzyme) release by IL-1-stimulated chondrocytes after introduction of hyaluronate was evaluated by use of sodium dodecyl sulfate agar gel electrophoresis of cartilage-conditioned media. The quantity or the molecular weight profile of IL-1-induced proteins did not differ after introduction of hyaluronate into the culture system. Results indicate that introduction of high molecular weight hyaluronate into cartilage culture systems results in a decrease in proteoglycan release from the matrix in control systems, as well as in cultures incubated with IL-1. Because IL-1-StiMUlated protein synthesis by chondrocytes remains unchanged after addition of exogenous hyaluronate, the mechanism of inhibition of matrix degradation does not appear to be interference with binding of IL-1 to chondrocytes or to be inhibition of the production of neutral metalloproteases, including stromelysin. C1 MASSACHUSETTS GEN HOSP,ORTHOPED RES LABS,BOSTON,MA 02114. RP MORRIS, EA (reprint author), TUFTS UNIV,SCH VET MED,DEPT MED,N GRAFTON,MA 01536, USA. NR 28 TC 46 Z9 46 U1 0 U2 2 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD NOV PY 1992 VL 53 IS 11 BP 1977 EP 1982 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA JV824 UT WOS:A1992JV82400001 PM 1466488 ER PT J AU ZAPOL, WM AF ZAPOL, WM TI VOLOTRAUMA AND THE INTRAVENOUS OXYGENATOR IN PATIENTS WITH ADULT RESPIRATORY-DISTRESS SYNDROME SO ANESTHESIOLOGY LA English DT Editorial Material DE COMPLICATIONS, VOLOTRAUMA; LUNGS, ADULT RESPIRATORY DISTRESS SYNDROME ID AIRWAY PRESSURE; VENTILATION; FAILURE; VOLUME RP ZAPOL, WM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 18 TC 22 Z9 23 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1992 VL 77 IS 5 BP 847 EP 849 DI 10.1097/00000542-199211000-00002 PG 3 WC Anesthesiology SC Anesthesiology GA JX504 UT WOS:A1992JX50400002 PM 1443735 ER PT J AU TONNER, PH POPPERS, DM MILLER, KW AF TONNER, PH POPPERS, DM MILLER, KW TI THE GENERAL ANESTHETIC POTENCY OF PROPOFOL AND ITS DEPENDENCE ON HYDROSTATIC-PRESSURE SO ANESTHESIOLOGY LA English DT Article DE POTENCY, ANESTHETIC, MEYER-OVERTON CORRELATION; OCTANOL WATER PARTITION COEFFICIENT; PRESSURE REVERSAL; ANESTHETICS, INTRAVENOUS, PROPOFOL ID LIPID BILAYERS; REVERSAL; PHARMACOKINETICS; PHARMACODYNAMICS; SITES AB Although plasma concentrations of propofol during anesthesia are well known, the free concentration remains unknown because of uncertainties regarding plasma protein binding, interaction with other protein-bound substances, the level of binding to its lipid carrier, and the use of adjuvants. At elevated surrounding pressure, all general anesthetics require higher concentrations to reach adequate levels of anesthesia. To determine the anesthetic potency of propofol at equilibrium conditions and to study the effects of pressure on propofol-induced anesthesia, Rana pipiens tadpoles were exposed to different concentrations of pure, not emulsified, propofol in aqueous solution. Anesthesia was defined as loss of the righting reflex. Ten animals per concentration were used, and each experiment was conducted twice. Pressure experiments were performed with nonanesthetized tadpoles and urethane-anesthetized tadpoles as control groups. Propofol concentrations were measured spectrophotometrically. At 1 atmosphere absolute (atm abs), a semilogarithmic sigmoidal concentration-response curve was obtained with a half-maximal effect of propofol at 2.2 +/- 0.22 muM (EC50; mean +/- SE). Increased pressure shifted the concentration-response curve to the right. The EC50 increased linearly with increasing pressure up to 121 atm abs (EC50 at 121 atm abs = 4.1 +/- 0.41 muM). For pressure greater than 121 atm abs, an increased excitability of the tadpoles made it difficult to distinguish the righting reflex from involuntary movements. The saturated solubility of propofol in aqueous solution was found to be 1.0 +/- 0.02 mM (mean +/- SD), and the octanol/water partition coefficient was 4,300 +/- 280. Propofol adhered to the correlation between anesthetic potency and octanol/water partition coefficient exhibited by other general anesthetics. Thus, it behaves like a typical general anesthetic in that it obeys the Meyer-Overton rule and its effects are reversed by increased pressure. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIGMS NIH HHS [GM15904] NR 22 TC 51 Z9 51 U1 1 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 1992 VL 77 IS 5 BP 926 EP 931 DI 10.1097/00000542-199211000-00015 PG 6 WC Anesthesiology SC Anesthesiology GA JX504 UT WOS:A1992JX50400015 PM 1443748 ER PT J AU WILLIAMS, JW SIMEL, DL ROBERTS, L SAMSA, GP AF WILLIAMS, JW SIMEL, DL ROBERTS, L SAMSA, GP TI CLINICAL-EVALUATION FOR SINUSITIS - MAKING THE DIAGNOSIS BY HISTORY AND PHYSICAL-EXAMINATION SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE SINUSITIS; TRANSILLUMINATION; RHINITIS; DIAGNOSIS, DIFFERENTIAL; TOOTHACHE ID ACUTE MAXILLARY SINUSITIS; BACTERIAL SINUSITIS AB Objective: To identify the most useful clinical examination findings for the diagnosis of acute and subacute sinusitis. Design: Prospective comparison of clinical findings with radiographs. Setting: General medicine clinics at a university-affiliated Veterans Affairs Medical Center. Patients: Two hundred forty-seven consecutive adult men with rhinorrhea (51%), facial pain (22%), or self-suspected sinusitis (27%) (median age, 50 years; median duration of symptoms, 11.5 days). Measurements: Patients were examined by a principal investigator (86%) or by a staff general internist, internal medicine resident (postgraduate year 2 or 3), or physician assistant, all blinded to radiographic results. All examiners recorded the presence or absence of 16 historical items, 5 physical examination items, and the clinical impression for sinusitis (high, intermediate, or low probability). The criterion standard was paranasal sinus radiographs (4 views), which were interpreted by radiologists blinded to clinical findings. Results: Thirty-eight percent of patients meeting entrance criteria had sinusitis. Sensitivity, specificity, and likelihood ratios were measured for clinical items. Logistic regression analysis showed five independent predictors of sinusitis: maxillary toothache (odds ratio, 2.9), transillumination (odds ratio, 2.7), poor response to nasal decongestants or antihistamines (odds ratio, 2.4), colored nasal discharge reported by the patient (odds ratio, 2.2), or mucopurulence seen during examination (odds ratio, 2.9). The overall clinical impression was more accurate than any single finding: high probability (likelihood ratio, 4.7), intermediate (likelihood ratio, 1.4), low probability (likelihood ratio, 0.4). Conclusions: General internists, focusing on five clinical findings and their overall clinical impression, can effectively stratify male patients with sinus symptoms as having a high, intermediate, or low probability of sinusitis. C1 VET ADM MED CTR,DURHAM,NC 27705. DUKE UNIV,MED CTR,DURHAM,NC 27710. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. RP WILLIAMS, JW (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,11C,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 34 TC 157 Z9 160 U1 0 U2 1 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 NOV 1 PY 1992 VL 117 IS 9 BP 705 EP 710 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA JV424 UT WOS:A1992JV42400001 PM 1416571 ER PT J AU GELBER, RD COATES, AS GOLDHIRSCH, A AF GELBER, RD COATES, AS GOLDHIRSCH, A TI METAANALYSIS - THE FASHION OF SUMMING-UP EVIDENCE .2. INTERPRETATIONS AND USES SO ANNALS OF ONCOLOGY LA English DT Article DE METAANALYSIS; OVERVIEW; CLINICAL TRIALS; BREAST CANCER; ARITHMETIC CONSTRUCT; INDIRECT COMPARISONS; SUBGROUP ANALYSIS ID RANDOMIZED CLINICAL-TRIALS; BREAST-CANCER; METAANALYSIS AB In this commentary, we use evidence produced by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) ten-year update of a meta-analysis of trials of adjuvant therapies for early breast cancer which started prior to 1985 to illustrate aspects of interpretations and uses of meta-analysis results. The following issues are discussed: i) The meta-analysis provides an average summary for the effect of a treatment. Greater statistical power is obtained by increasing the number of events contributing to the analysis. However, summing up the results of various trials necessitates the loss of individual information concerning the magnitude of treatment effects which depend on tumor- and patient-related factors. Subgroup analyses within the meta-analysis process allow some recovery of such features; ii) The absolute benefit obtained from an effective treatment depends not only on the relative benefit of the treatment but also on the prognosis of the individual patients; iii) The results are more immediately applicable if less reliance is placed on the arithmetic construct inherent in the overview, using instead unconfounded information about the value of treatments actually administered. This avoids the need to extrapolate the effect for one component of the therapy by assuming a lack of interaction with its other components; iv) Although indirect comparisons between different meta-analyses are regularly made to pick the "winner" from among tested treatment modalities, it is unlikely that the optimal therapeutic regimen can be defined via such indirect comparisons. though such comparisons may raise interesting, testable hypotheses. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. ROYAL PRINCE ALFRED HOSP,ANZ BREAST CANC TRIALS GRP,SYDNEY,NSW,AUSTRALIA. UNIV SYDNEY,DEPT MED,SYDNEY,NSW 2006,AUSTRALIA. OSPED CIVICO,INT BREAST STUDY GRP,LUGANO,SWITZERLAND. RP GELBER, RD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT & EPIDEMIOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-06516] NR 19 TC 6 Z9 6 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 1992 VL 3 IS 9 BP 683 EP 691 PG 9 WC Oncology SC Oncology GA JW882 UT WOS:A1992JW88200010 PM 1450057 ER PT J AU SPATARO, V PRICE, K GOLDHIRSCH, A CAVALLI, F SIMONCINI, E CASTIGLIONE, M RUDENSTAM, CM COLLINS, J LINDTNER, J GELBER, RD AF SPATARO, V PRICE, K GOLDHIRSCH, A CAVALLI, F SIMONCINI, E CASTIGLIONE, M RUDENSTAM, CM COLLINS, J LINDTNER, J GELBER, RD TI SEQUENTIAL ESTROGEN-RECEPTOR DETERMINATIONS FROM PRIMARY BREAST-CANCER AND AT RELAPSE - PROGNOSTIC AND THERAPEUTIC RELEVANCE SO ANNALS OF ONCOLOGY LA English DT Article DE BREAST CANCER; ESTROGEN RECEPTOR; OVERALL SURVIVAL; PRIMARY AND SECONDARY CARCINOMA; PROGNOSTIC FACTORS; SEQUENTIAL DETERMINATIONS ID PROGESTERONE-RECEPTOR; ADJUVANT CHEMOTHERAPY; ENDOCRINE THERAPY; PAST DECADE; ASSAYS; TAMOXIFEN; MULTIPLE; ESTRADIOL AB We retrospectively evaluated 401 selected patients who had estrogen receptor (ER) assays both at primary surgery and at relapse in an accessible site to determine the clinical relevance of the subsequent ER determination. The median time between ER assessments was 27 months (range: 2-122 months). The median follow-up time from diagnosis was 6 years (range: 2-12 years). For patients with ER+ tumors at primary diagnosis, 29% (76/261) had ER- tumors at relapse, while for ER- primaries, the conversion rate was 33% (46/140). Conversions from ER+ to ER- occurred more often when the time interval between assays was less than one year (p = 0.004), while conversions from ER- to ER+ tended to occur late (beyond three years; p = 0.0003). Treatments received between assays (usually adjuvant therapy) had only a slight influence on ER status conversion. Post-relapse survival was poor for patients who had the biopsy accessible recurrence within one year; an expression of the aggressive nature of the disease. Among patients whose accessible relapse was beyond one year, those with ER- primaries who converted to ER+ had a longer survival than those whose recurrence was classified again as ER- (p = 0.006). This group of patients with ER- primaries who recurred beyond one year with an ER+ tumor in an accessible site represented 29% (40/140) of all patients with ER- primaries, and had an estimated overall survival rate of more than 60% at 6 years from the accessible relapse. ER determination upon relapse within one year has very little clinical relevance. We conclude that, based on an experience in a selected population, reassessment of ER status upon relapse is of little clinical value for patients who recur within one year from initial diagnosis, but is important for patients who recur beyond one year especially for those with ER- primaries. C1 OSPED CIVICO,INT BREAST CANC STUDY GRP,CH-6900 LUGANO,SWITZERLAND. OSPED SAN GIOVANNI BELLINZONA,DIV ONCOL,BELLINZONA,SWITZERLAND. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. SPEDALI CIVIL BRESCIA,DEPT ONCOL,DIV MED 3,BRESCIA,ITALY. SPEDALI CIVIL BRESCIA,BERETTA FDN RES & TREATMENT CANC,BRESCIA,ITALY. UNIV BERN,INSELSPITAL,INST MED ONCOL,CH-3010 BERN,SWITZERLAND. W SWEDISH BREAST CANC STUDY GRP,GOTHENBURG,SWEDEN. AUSTRALIA NEW ZEALAND BREAST CANC STUDY GRP,MELBOURNE,AUSTRALIA. INST ONCOL,LJUBLJANA,YUGOSLAVIA. NR 47 TC 50 Z9 52 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 1992 VL 3 IS 9 BP 733 EP 740 PG 8 WC Oncology SC Oncology GA JW882 UT WOS:A1992JW88200019 PM 1450062 ER PT J AU FALKSON, G GELMAN, RS GLICK, J FALKSON, CI HARRIS, J AF FALKSON, G GELMAN, RS GLICK, J FALKSON, CI HARRIS, J TI METASTATIC BREAST-CANCER - HIGHER VERSUS LOW-DOSE MAINTENANCE TREATMENT WHEN ONLY A PARTIAL RESPONSE OR A NO CHANGE STATUS IS OBTAINED FOLLOWING DOXORUBICIN INDUCTION TREATMENT SO ANNALS OF ONCOLOGY LA English DT Note DE BREAST CANCER; MAINTENANCE; METASTATIC; PARTIAL RESPONSE ID COOPERATIVE-ONCOLOGY-GROUP C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HOSP UNIV PENN,PHILADELPHIA,PA 19104. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. RP FALKSON, G (reprint author), UNIV PRETORIA,DEPT MED ONCOL,POB 667,PRETORIA 0001,SOUTH AFRICA. FU NCI NIH HHS [CA 23318, CA 21692, CA 21115] NR 3 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 1992 VL 3 IS 9 BP 768 EP 770 PG 3 WC Oncology SC Oncology GA JW882 UT WOS:A1992JW88200024 PM 1450067 ER PT J AU EAVEY, RD CHAPMAN, PH WEBER, A SWEARINGEN, B DAVIS, KR JANFAZA, P LIEBSCH, N FERGUSON, WS AF EAVEY, RD CHAPMAN, PH WEBER, A SWEARINGEN, B DAVIS, KR JANFAZA, P LIEBSCH, N FERGUSON, WS TI SKULL BASE DUMBBELL TUMOR - SURGICAL EXPERIENCE WITH 2 ADOLESCENTS SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE CHONDROSARCOMA; MIDDLE FOSSA APPROACH; PEDIATRIC SKULL BASE TUMOR; SKULL BASE DUMBBELL TUMOR; SKULL BASE SURGERY; SPINDLE CELL SARCOMA ID INFRATEMPORAL FOSSA APPROACH; MANAGEMENT AB Pediatric skull base tumors are rare and until recently were considered unresectable. We present two patients with tumors of similar anatomic position with an extracranial component in the infratemporal fossa and parapharyngeal space, an isthmus at the foramen ovale, and a superior component in the middle cranial fossa in the region of the cavernous sinus. A 15-year-old girl experienced contiguous spread of a spindle cell sarcoma; an 18-year-old boy developed a chondrosarcoma. A middle fossa approach provided the advantage of surgical avoidance of structures such as the middle ear and mastoid, facial nerve, and mandible. Postoperative recovery was rapid. Our impression is that preoperative carotid artery occlusion and a middle fossa approach for tumor resection can be performed in a young patient with acceptable morbidity and at least short-term benefit. Surgery can, therefore, provide an additional therapeutic approach to complement irradiation and chemotherapy. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT MED,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02114. RP EAVEY, RD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD NOV PY 1992 VL 101 IS 11 BP 939 EP 945 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA JY435 UT WOS:A1992JY43500010 PM 1444102 ER PT J AU MUEHRCKE, DD DAGGETT, WM BUCKLEY, MJ AKINS, CW HILGENBERG, AD AUSTEN, WG KAY, GL PIWNICA AF MUEHRCKE, DD DAGGETT, WM BUCKLEY, MJ AKINS, CW HILGENBERG, AD AUSTEN, WG KAY, GL PIWNICA TI POSTINFARCT VENTRICULAR SEPTAL-DEFECT REPAIR - EFFECT OF CORONARY-ARTERY BYPASS-GRAFTING SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 28TH ANNUAL MEETING OF THE SOC OF THORACIC SURGEONS CY FEB 03-05, 1992 CL ORLANDO, FL SP SOC THORAC SURGEONS ID MITRAL-VALVE REPLACEMENT; MYOCARDIAL-INFARCTION; SURGICAL-MANAGEMENT; RUPTURE; DETERMINANTS AB Between June 1968 and April 1991, 75 patients who had undergone coronary angiography underwent repair of a postinfarction ventricular septal defect. Group 1 (n = 33) includes patients who had two- or three-vessel serious (>75% narrowing) proximal coronary artery disease and underwent complete revascularization in addition to repair of the ventricular septal defect. Group 2 (n = 19) patients also had two- or three-vessel coronary artery disease but bypass grafting was not performed; only the ventricular defect was repaired. Group 3 (n = 23) patients had only single-vessel coronary artery disease that corresponded to the region of the infarct; they underwent ventricular septal defect repair only. Follow-up of hospital survivors was 96% complete at a mean of 86.2 months (range, 1 to 288 months). Hospital mortality after ventricular septal defect repair was 21.2% in the cohort with bypassed coronary artery disease (group 1), 26.3% in those with unbypassed disease (group 2), and 26.1% in those with only single-vessel coronary artery disease (group 3) (p = 0. 88). With follow-up after 5 and 10 years, the actuarial survival was 72.2% +/- 8% and 47.8% +/- 10%, respectively, in the bypassed group, 29.2% +/- 11% and 0%, respectively, in the unbypassed group, and 52.2% +/-10% and 36.5% +/- 11%, respectively, in the cohort with single-vessel disease. Bypassing associated coronary artery disease significantly increased long-term survival when compared with patients with unbypassed coronary artery disease (p = 0.0015). C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG CARDIOVASC UNIT,BOSTON,MA 02114. NR 26 TC 39 Z9 43 U1 1 U2 1 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 NOV PY 1992 VL 54 IS 5 BP 876 EP 883 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA JV617 UT WOS:A1992JV61700010 PM 1417278 ER PT J AU BAER, L JENIKE, MA BLACK, DW TREECE, C ROSENFELD, R GRIEST, J AF BAER, L JENIKE, MA BLACK, DW TREECE, C ROSENFELD, R GRIEST, J TI EFFECT OF AXIS-II DIAGNOSES ON TREATMENT OUTCOME WITH CLOMIPRAMINE IN 55 PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PERSONALITY-DISORDER; MAJOR DEPRESSION; PANIC DISORDER; INTERVIEW; VALIDITY; FEATURES; SCALE AB We used the Structured Interview for DSM-III Personality Disorders to diagnose DSM-III personality disorders systematically in 55 patients with obsessive-compulsive disorder in the active-treatment cell of a controlled trial of clomipramine hydrochloride. Patients with a cluster A personality disorder had significantly higher obsessive-compulsive disorder severity scores at baseline, and the number of personality disorders was strongly related to baseline severity of obsessive-compulsive disorder symptoms. At the conclusion of the 12-week study, we found no significant difference in treatment outcome with clomipramine between those patients with at least one personality disorder and those with no personality disorders. However, the presence of schizotypal, borderline, and avoidant personality disorders, along with total number of personality disorders, did predict poorer treatment outcome. These variables were strongly related to having at least one cluster A personality disorder diagnosis, which was also a strong predictor of poorer outcome. Implications of these findings are discussed. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV IOWA,DEPT PSYCHIAT,IOWA CITY,IA 52242. UNIV WISCONSIN,DEPT PSYCHIAT,MADISON,WI 53706. NR 39 TC 143 Z9 144 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 1992 VL 49 IS 11 BP 862 EP 866 PG 5 WC Psychiatry SC Psychiatry GA JX303 UT WOS:A1992JX30300003 PM 1444723 ER PT J AU VOLPICELLI, JR ALTERMAN, AI HAYASHIDA, M OBRIEN, CP AF VOLPICELLI, JR ALTERMAN, AI HAYASHIDA, M OBRIEN, CP TI NALTREXONE IN THE TREATMENT OF ALCOHOL DEPENDENCE SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ETHANOL-CONSUMPTION; RATS; DISULFIRAM; NALOXONE AB Seventy male alcohol-dependent patients participated in a 12-week, double-blind, placebo-controlled trial of naltrexone hydrochloride (50 mg/d) as an adjunct to treatment following alcohol detoxification. Subjects taking naltrexone reported significantly less alcohol craving and days in which any alcohol was consumed. During the 12-week study, only 23% of the naltrexone-treated subjects met the criteria for a relapse, whereas 54.3% of the placebo-treated subjects relapsed. The primary effect of naltrexone was seen in patients who drank any alcohol while attending outpatient treatment. Nineteen (95%) of the 20 placebo-treated patients relapsed after they sampled alcohol, while only eight (50%) of 16 naltrexone-treated patients exposed to alcohol met relapse criteria. Naltrexone was not associated with mood changes or other psychiatric symptoms. Significant side effects (nausea) occurred in two naltrexone-treated subjects, and one naltrexone-treated subject complained of increased pain from arthritis. These results suggest that naltrexone may be a safe and effective adjunct to treatment in alcohol-dependent subjects, particularly in preventing alcohol relapse. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. FU NIAAA NIH HHS [AA0751701A1]; NIDA NIH HHS [DA05186] NR 22 TC 1233 Z9 1259 U1 10 U2 36 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 1992 VL 49 IS 11 BP 876 EP 880 PG 5 WC Psychiatry SC Psychiatry GA JX303 UT WOS:A1992JX30300006 PM 1345133 ER PT J AU GRAFTON, ST MAZZIOTTA, JC PAHL, JJ STGEORGEHYSLOP, P HAINES, JL GUSELLA, J HOFFMAN, JM BAXTER, LR PHELPS, ME AF GRAFTON, ST MAZZIOTTA, JC PAHL, JJ STGEORGEHYSLOP, P HAINES, JL GUSELLA, J HOFFMAN, JM BAXTER, LR PHELPS, ME TI SERIAL CHANGES OF CEREBRAL GLUCOSE-METABOLISM AND CAUDATE SIZE IN PERSONS AT RISK FOR HUNTINGTONS-DISEASE SO ARCHIVES OF NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY; PHENOTYPIC VARIATION; DIAGNOSIS; LINKAGE; HUMANS; AGE; CHROMOSOME-4; VALIDATION; FAMILIES AB Objective.-To determine the rate of change of glucose metabolism and caudate size in persons at risk for Huntington's disease. Design-Eighteen persons at risk for Huntington's disease had two positron emission tomographic glucose metabolic studies and two magnetic resonance imaging scans separated by 42 (+/-9) months. Setting.-Ambulatory research subjects at a teaching hospital with magnetic resonance imaging and positron emission tomographic technology. Subjects.-Seven of the individuals were Huntington' disease gene negative by testing at the polymorphic DNA loci D4S10, D4S43, and D4S125; the remainder were gene positive by genetic testing or onset of chorea after study entry. Interventions.-None. Outcome Measures.-Onset of chorea and imaging results. Results.-The gene-positive group demonstrated a significant 3.1% loss of glucose metabolic rate per year in the caudate nucleus (95% confidence interval [CI], -4.64, -1.48) compared with the gene-negative group. There was a 3.6% per year increase in the magnetic resonance imaging bicaudate ratio (95% CI, 1.81, 5.37), a linear measure of caudate atrophy. The rate of change in caudate size did not correlate with the rate of change in caudate metabolism, suggesting that metabolic loss and atrophy may develop independently. Conclusions.-The results suggest that a reduction in caudate glucose metabolism and atrophy develop rapidly in Huntington's disease. The findings establish a strategy for using serial positron emission tomographic imaging to monitor experimental pharmacologic interventions in presymptomatic individuals who have developed caudate hypometabolism. C1 UNIV CALIF LOS ANGELES,SCH MED,DIV NUCL MED & BIOPHYS,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT ENERGY,NUCL MED LAB,LOS ANGELES,CA 90024. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114. UNIV OKLAHOMA,DEPT PSYCHIAT,OKLAHOMA CITY,OK. DUKE UNIV,DIV NUCL MED,DURHAM,NC 27706. UNIV TORONTO,DEPT NEUROL,TORONTO M5S 1A1,ONTARIO,CANADA. UNIV TORONTO,DEPT MED,TORONTO M5S 1A1,ONTARIO,CANADA. RP GRAFTON, ST (reprint author), UNIV SO CALIF,SCH MED,DEPT NEUROL,1510 SAN PABLO AVE,LOS ANGELES,CA 90033, USA. RI Haines, Jonathan/C-3374-2012 FU NIMH NIH HHS [MH00752]; NINDS NIH HHS [NS16367, P01-NS-15654] NR 45 TC 103 Z9 103 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 1992 VL 49 IS 11 BP 1161 EP 1167 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA JW864 UT WOS:A1992JW86400015 PM 1444883 ER PT J AU FRANK, JI ROPPER, AH ZUNIGA, G AF FRANK, JI ROPPER, AH ZUNIGA, G TI ACUTE INTRACRANIAL LESIONS AND RESPIRATORY SINUS ARRHYTHMIA SO ARCHIVES OF NEUROLOGY LA English DT Article ID HEART-PERIOD VARIABILITY; PHARMACOLOGICAL MANIPULATIONS; INFLATION; REFLEX AB We studied the effects of acute intracranial lesions on the respiratory sinus arrhythmia (RSA) with the use of computerized measurements of the ratio of expiratory to inspiratory R-R intervals. The RSA was reduced below the 95th percentile for age in 20 of 27 patients, an average of 2 days after an acute event. Only four patients, without neurological deficits, had a normal RSA. Two patients, with signs of secondary brain-stem compression from a mass, had an increased RSA, without the bradycardia that is usually associated with Cushing's response. Twenty-three patients had their respiratory rate controlled by positive pressure ventilation during testing, and our preliminary findings suggested that this was not responsible for reducing the RSA. Acute intracranial lesions cause a diminished RSA, perhaps by reducing supratentorial influences on vagal cardioinhibitory activity. in contrast, once signs of secondary brain-stem compression occur, the RSA is greatly increased while the heart rate remains unchanged, offering a possible method of noninvasive monitoring for this complication. C1 MASSACHUSETTS GEN HOSP,NEUROMED NEUROSURG INTENS CARE UNIT,BOSTON,MA 02114. ST ELIZABETH HOSP,DIV NEUROL,WASHINGTON,DC 20032. NR 20 TC 11 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 1992 VL 49 IS 11 BP 1200 EP 1203 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA JW864 UT WOS:A1992JW86400020 PM 1444888 ER PT J AU MATTHEWS, GP SANDBERG, MA BERSON, EL AF MATTHEWS, GP SANDBERG, MA BERSON, EL TI FOVEAL CONE ELECTRORETINOGRAMS IN PATIENTS WITH CENTRAL VISUAL-LOSS OF UNEXPLAINED ETIOLOGY SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID JUVENILE MACULAR DEGENERATION; RETINITIS PIGMENTOSA; EYES AB Foveal cone electroretinograms (ERGs) were recorded in five patients (aged 24 to 66 years) referred because of central visual loss of unexplained etiology. These patients had no family history of visual loss and no diagnostic fundus abnormalities seen on ophthalmoscopy or fluorescein angiography. Foveal cone ERGs were elicited with a 4-degrees white stimulus flickering at 42 Hz centered within a steady 10-degrees white surround presented through the dilated pupil to the fovea by a hand-held, dual-beam stimulator-ophthalmoscope. All five patients showed reduced foveal cone ERG amplitudes. Their abnormal responses were similar to those previously reported in cases of clinically apparent macular degeneration and contrasted with previously reported normal responses in patients with optic atrophy or strabismic amblyopia. The progressive loss of central vision as determined by history and these subnormal foveal cone ERG amplitudes suggest that these patients have a form of macular degeneration. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. FU NEI NIH HHS [EY08398] NR 16 TC 27 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 NOV PY 1992 VL 110 IS 11 BP 1568 EP 1570 PG 3 WC Ophthalmology SC Ophthalmology GA JX321 UT WOS:A1992JX32100016 PM 1444913 ER PT J AU AKITA, H FUKAE, M SHIMODA, S AOBA, T AF AKITA, H FUKAE, M SHIMODA, S AOBA, T TI LOCALIZATION OF GLYCOSYLATED MATRIX PROTEINS IN SECRETORY PORCINE ENAMEL AND THEIR POSSIBLE FUNCTIONAL ROLES IN ENAMEL MINERALIZATION SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE AMELOGENESIS; ENAMEL PROTEINS; GLYCOSYLATION; LECTINS; ENAMEL MINERALIZATION ID AMELOGENIN; TOOTH; HETEROGENEITY; RAT AB The present study was undertaken to investigate glycosylation of porcine enamel proteins secreted in the secretory stage of amelogenesis and to gain insight into functional roles of glycosylated proteins in enamel mineralization. Enamel proteins, isolated from various zones of the secretory enamel, were separated by SDS-PAGE and then transferred on to a nitrocellulose membrane. The transblotted proteins were visualized with either antibodies against porcine amelogenins or various biotin-conjugated lectins. The lectins used were Con-A, GS-II, STA, WGA, s-WGA, GS-I, MPA, WA, PNA, RCA-I, DBA, SJA, UEA-I, Lotus-A and LPA. The results of the immuno- and lectin blottings revealed that most of the lectins did not bind to porcine amelogenins, while a large number of non-amelogenins having various molecular masses were stained strongly with the conjugated WGA, Con A and MPA lectins. On the basis of the binding specificity with the lectins, porcine non-amelogenins were classified into two groups: WGA (and Con A)-binding moieties at 60-90 kDa (WGA-HMW); and MPA-binding moieties at 13-17 kDa (MPA-LMW). These two groups of non-amelogenins differed distinctly in terms of their localization and stability in the secretory tissue and their adsorption properties onto hydroxyapatite. The WGA-HMW were concentrated in the outer region adjacent to the ameloblasts and disappeared (due to degradation) in the underlying inner secretory enamel. In contrast, the MPA-LMW were found in all zones of the secretory enamel and their quantity remained relatively constant. Histochemical studies using FITC-conjugated WGA and MPA showed that the fluorescence-labelling of WGA was localized in the core region of prism rods, while the fluorescence-labelling of MPA was locally limited at the rim of prism rods or at the prism sheath. In separate adsorption studies, it was found that the WGA-HMW, as well as the intact amelogenins, displayed a high adsorption affinity on to apatite crystals, whereas the MPA-LMW showed only marginal adsorption on to apatitic surfaces. The overall results indicate that part of the heterogeneity found in porcine enamel proteins can be ascribed to variations of carbohydrate moieties attached to non-amelogenins. As to possible functional roles of porcine enamel proteins, the results strongly suggest that the WGA-HMW non-amelogenins and the intact amelogenins participate directly in regulation of the precipitation and growth of enamel crystals taking place in the vicinity of the ameloblasts, while the MPA-LMW non-amelogenins may contribute to development of a well-organized enamel structure by supporting a framework of prism rods. C1 FORSYTH DENT CTR,140 FENWAY,BOSTON,MA 02115. TSURUMI UNIV,FAC DENT,YOKOHAMA 230,JAPAN. FU NIDCR NIH HHS [DE07623] NR 23 TC 39 Z9 39 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD NOV PY 1992 VL 37 IS 11 BP 953 EP 962 DI 10.1016/0003-9969(92)90067-I PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JZ889 UT WOS:A1992JZ88900013 PM 1334650 ER PT J AU EAVEY, RD CAMACHO, A NORTHROP, CC AF EAVEY, RD CAMACHO, A NORTHROP, CC TI CHRONIC EAR PATHOLOGY IN A MODEL OF NEONATAL AMNIOTIC-FLUID EAR INOCULATION SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID MIDDLE-EAR; GUINEA-PIGS; CHOLESTEATOMA AB Human histopathologic studies have demonstrated that amniotic fluid cellular contents, keratinized squamous epithelial cells and lanugo hair, induce an intense inflammatory reaction including granulation tissue in the neonatal temporal bone. To investigate this reaction over a prolonged period, an animal model was studied. An aliquot of sterilized autologous hair and keratinized epithelial cells was placed into 14 gerbil bullae; saline was used as a contralateral control. The animals were sacrificed at intervals up to 6 months and the temporal bones were studied by light microscopy. All animals demonstrated nonpurulent inflammatory changes on the experimental side including granulation tissue, osteoneogenesis, tympanosclerosis, and cholesteatoma; the control side demonstrated minimal middle ear changes. We conclude that in this model autologous keratinized tissue provokes a foreign body response similar to the granulation tissue observed in human infants and, further, that over a prolonged period the middle ear demonstrates more severe pathologic consequences. C1 UNIV DEL VALLE,DEPT OTORHINOLARYNGOL,CALI,COLOMBIA. HOSP NACL NINOS DR CARLOS SAENZ HERRERA,DEPT PATHOL,SAN JOSE,COSTA RICA. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP EAVEY, RD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 29 TC 5 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 1992 VL 118 IS 11 BP 1198 EP 1203 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA JX324 UT WOS:A1992JX32400012 PM 1384561 ER PT J AU CURRIE, DM GILBERT, D DIERSCHKE, BJ AF CURRIE, DM GILBERT, D DIERSCHKE, BJ TI AEROBIC CAPACITY WITH 2 LEG WORK VERSUS ONE LEG PLUS BOTH ARMS WORK IN MEN WITH PERIPHERAL VASCULAR-DISEASE SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE EXERCISE TEST; HUMAN; OXYGEN CONSUMPTION; REHABILITATION; VASCULAR DISEASES ID EXERCISE AB The purpose of this pilot study Aas to examine the correlation between ergometry in men with peripheral vascular disease exercising with both legs and with one leg and both arms. Fifteen men with peripheral vascular disease performed three symptom-limited exercise tests on an ergometer that could be operated from a wheelchair with both legs or with one leg and both arms. The three exercise conditions were both legs (arms stabilized), left leg plus both arms, and right leg plus both arms. The exercise parameters compared were maximum oxygen consumption, maximum heart rate, and duration of exercise. Blood pressure was monitored at two-minute intervals and oxygen saturation and electrocardiogram were monitored continuously. The mean VO2max +/- standard deviation for both legs, right leg plus both arms, and left leg plus both arms were 14.36 +/- 6.15, 14.86 +/- 4.09, 14.01 +/- 4.14ml O2/kg-min, respectively. The mean duration of exercise +/- standard deviation were 12.01 +/- 5.74, 10.94 +/- 4.68, and 9.81 +/- 4.70 minutes respectively. The mean maximum heart rate +/- standard deviation were 126 +/- 24, 137 +/- 23, 136 +/- 23, respectively for the same exercise conditions. The Pearson Correlation Coefficients for VO2 for both legs versus right leg plus both arms and left leg plus both arms were .639 and .873, respectively. The Pearson Correlation Coefficients for duration of exercise for both legs versus right leg plus both arms and left leg plus both arms were .837 and .877, respectively. The Pearson Correlation Coefficients for maximum heart rate for both legs versus right leg plus both arms and left leg plus both arms were .804 and .882, respectively. These data establish strong correlations between measures of exercise capacity with both legs versus one leg plus both arms in these men with peripheral vascular disease with no amputation. The data suggest that the methods described here for ergometry with one leg plus both arms are a valid measure of exercise capacity in unilateral lower extremity amputees. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. GUNDERSON CLIN LTD,LA CROSSE,WI 54601. RP CURRIE, DM (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DEPT REHABIL MED,SAN ANTONIO,TX, USA. NR 11 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 1992 VL 73 IS 11 BP 1081 EP 1084 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA JX141 UT WOS:A1992JX14100010 PM 1444776 ER PT J AU BOTTINGER, EP NILES, JL COLLINS, AB MCCLUSKEY, RT ARNAOUT, MA AF BOTTINGER, EP NILES, JL COLLINS, AB MCCLUSKEY, RT ARNAOUT, MA TI ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY-ASSOCIATED VASCULITIS PRESENTING AS SJOGRENS-SYNDROME SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SALIVARY-GLAND INVOLVEMENT; WEGENERS GRANULOMATOSIS; ANTIBODIES AB A 63-year-old woman, in whom a diagnosis of Sjogren's syndrome was initially made, proved to have systemic vasculitis with salivary gland involvement and necrotizing and crescentic glomerulonephritis. Antineutrophil cytoplasmic autoantibodies (ANCA) against myeloperoxidase were positive. ANCA-associated vasculitis should be considered in the differential diagnosis of Sjogren's syndrome. A positive finding on immunoassay for ANCA against myeloperoxidase or proteinase 3 may help establish the diagnosis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LEUKOCYTE BIOL & INFLAMMAT PROGRAM,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-42722] NR 14 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 1992 VL 35 IS 11 BP 1373 EP 1376 PG 4 WC Rheumatology SC Rheumatology GA JW730 UT WOS:A1992JW73000018 PM 1445456 ER PT J AU FERRUCCI, JT AF FERRUCCI, JT TI GALLBLADDER STONES - DIAGNOSTIC PROCEDURES SO BAILLIERES CLINICAL GASTROENTEROLOGY LA English DT Article ID SHOCK-WAVE LITHOTRIPSY; PREDICTING GALLSTONE COMPOSITION; INVITRO; CT; DISSOLUTION; SONOGRAPHY; INVIVO; NUMBER; SIZE RP FERRUCCI, JT (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3528 J9 BAILLIERE CLIN GASTR JI Baillieres Clin. Gastroenterol. PD NOV PY 1992 VL 6 IS 4 BP 659 EP 677 DI 10.1016/0950-3528(92)90045-G PG 19 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KH113 UT WOS:A1992KH11300003 PM 1486207 ER PT J AU MALT, RA AF MALT, RA TI GALLSTONES - ROLE OF SURGERY SO BAILLIERES CLINICAL GASTROENTEROLOGY LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY; PERCUTANEOUS CHOLECYSTOSTOMY; PARENTERAL-NUTRITION; ACUTE CHOLECYSTITIS; BILE-DUCT; GALLBLADDER; COMPLICATIONS; DIAGNOSIS; SYMPTOMS; DISEASE RP MALT, RA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 59 TC 1 Z9 1 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3528 J9 BAILLIERE CLIN GASTR JI Baillieres Clin. Gastroenterol. PD NOV PY 1992 VL 6 IS 4 BP 743 EP 765 DI 10.1016/0950-3528(92)90051-F PG 23 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA KH113 UT WOS:A1992KH11300009 PM 1486213 ER PT J AU LYDON, NB GAY, B METT, H MURRAY, B LIEBETANZ, J GUTZWILLER, A PIWNICAWORMS, H ROBERTS, TM MCGLYNN, E AF LYDON, NB GAY, B METT, H MURRAY, B LIEBETANZ, J GUTZWILLER, A PIWNICAWORMS, H ROBERTS, TM MCGLYNN, E TI PURIFICATION AND BIOCHEMICAL-CHARACTERIZATION OF NONMYRISTOYLATED RECOMBINANT PP60(C-SRC) KINASE SO BIOCHEMICAL JOURNAL LA English DT Article ID ROUS-SARCOMA VIRUS; PROTEIN-TYROSINE KINASE; TRANSFORMING PROTEIN; GROWTH-FACTOR; INSECT CELLS; SERINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; ESCHERICHIA-COLI; HUMAN-PLATELETS; SRC KINASE AB To obtain sufficient material for the biochemical and biophysical study of pp60c-src, we have utilized a recombinant pp60c-src baculovirus lacking the myristoylation site at codon 2. On infection of Sf9 cells, this virus produced large amounts of soluble non-myristoylated pp60c-src. The use of non-myristoylated pp60c-src (1) increases production of pp60c-src compared with the wild-type protein, (2) facilitates purification, (3) yields a stable product and (4) allows biochemical studies in the absence of detergents. Up to 20 mg of pp60c-src of greater than 95%, purity has been purified from 6 litres of Sf9 cells grown in a bioreactor. One major and multiple minor forms of pp60c-src were separated by Mono Q f.p.l.c. Isoelectric focusing of purified pp60c-src species revealed heterogeneity, some of which could be attributed to differences in the tyrosine phosphorylation state of the enzyme. Kinetic analysis of non-myristoylated pp60c-src kinase in the presence of Mg2+ gave K(m) values for angiotensin II and ATP of 2 mM and 30 muM respectively and a V(max) of 620 mmol/min per mg. The kinetic constants and metal ion preferences of a number of copolymers and peptide substrates have been compared. Polylysine and poly(GLAT), which was not phosphorylated by the pp60c-src kinase, dramatically activated autophosphorylation of Tyr-416, suggesting a conformation modulation of pp60c-src by charged polymers. This finding implies that Tyr-527 dephosphorylation is not sufficient for full activation of pp60c-src in vitro. C1 TUFTS UNIV,SCH MED,DEPT PHYSIOL,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP LYDON, NB (reprint author), CIBA GEIGY AG,RES DEPT,DIV PHARMACEUT,CH-4002 BASEL,SWITZERLAND. RI Piwnica-Worms, Helen/C-5214-2012 NR 61 TC 29 Z9 29 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 1992 VL 287 BP 985 EP 993 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW485 UT WOS:A1992JW48500045 PM 1280108 ER PT J AU SLINKIN, MA CURTET, C SAIMAUREL, C GESTIN, JF TORCHILIN, VP CHATAL, JF AF SLINKIN, MA CURTET, C SAIMAUREL, C GESTIN, JF TORCHILIN, VP CHATAL, JF TI SITE-SPECIFIC CONJUGATION OF CHAIN-TERMINAL CHELATING POLYMERS TO FAB' FRAGMENTS OF ANTI-CEA MAB - EFFECT OF LINKAGE TYPE AND POLYMER SIZE ON CONJUGATE BIODISTRIBUTION IN NUDE-MICE BEARING HUMAN COLORECTAL-CARCINOMA SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODIES; CARCINOEMBRYONIC ANTIGEN; IN-111 DTPA; TUMOR; LOCALIZATION; XENOGRAFTS; AGENTS; INVIVO; BLOOD AB Polylysine-based chelating polymers were used for site-specific modification of anti-CEA mAb Fab' fragments via their SH group distal to the antigen-binding site of the antibody molecule. Conjugation was performed using chain-terminal (pyridyldithio)propionate or 4-(p-maleimidophenyl)butyrate moieties to form reducible (S-S) or stable (S-C) bonds between a polymer and Fab' molecule, respectively. One S-S conjugate (S-S9) and two different S-C conjugates (S-C3 and S-C-9) were prepared using 3- and 9-kDa molecular weight polymers. No significant loss of immunoreactivity was observed in solid-phase immunoassay, 90-95% of In-111-labeled conjugates being bound to CEA-coated Sepharose beads. After labeling with In-111, the conjugates had a specific radioactivity of 90-120 muCi/mug. Injected in nude mice bearing LS 174T carcinoma, the conjugates produced different biodistribution patterns. S-S9 was practically unable to accumulate in tumor and produced very rapid blood clearance of radioactivity and high uptake of radioactivity in liver, spleen, and especially kidneys (225% ID/g 24 h postinjection). S-C3 and S-C-9 produced practically the same blood clearances (much slower than that of S-S9) and significant tumor uptake (9-10% ID/g at 24 h). S-C3 gave significantly lower radioactivity in spleen, skin, and bones, and cleared more rapidly from liver and kidneys. Renal uptake for S-C3 and S-C-9 was rather high (45% ID/g at 24 h), but much lower than for S-S9. C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02129. RP SLINKIN, MA (reprint author), PLATEAU TECH CHR,BIOPHYS CANCEROL LAB,INSERM,U211,F-44035 NANTES 01,FRANCE. RI GESTIN, Jean-Francois/M-1505-2015 NR 26 TC 4 Z9 4 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 1992 VL 3 IS 6 BP 477 EP 483 DI 10.1021/bc00018a003 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA KA511 UT WOS:A1992KA51100003 PM 1463777 ER PT J AU MYERS, KR ULRICH, JT QURESHI, N TAKAYAMA, K RONG, W LING, C EMARY, WB COTTER, RJ AF MYERS, KR ULRICH, JT QURESHI, N TAKAYAMA, K RONG, W LING, C EMARY, WB COTTER, RJ TI PREPARATION AND CHARACTERIZATION OF BIOLOGICALLY-ACTIVE 6'-O-(6-AMINOCAPROYL)-4'-O-MONOPHOSPHORYL LIPID-A AND ITS CONJUGATED DERIVATIVE SO BIOCONJUGATE CHEMISTRY LA English DT Article ID LIPOPOLYSACCHARIDE-BINDING PROTEINS; DESORPTION MASS-SPECTROMETRY; NUCLEAR MAGNETIC-RESONANCE; TUMOR NECROSIS FACTOR; STRUCTURAL DETERMINATION; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; CELLS; INDUCTION AB N-tert-butyloxycarbonyl (t-Boc) protected 6-aminocaproic (Cap) anhydride was reacted with unprotected hexaacyl-4'-O-monophosphoryl lipid A (MLA) obtained from the lipopolysaccharide of Escherichia coli J5 to yield t-Boc-Cap-MLA. After a column purification step, the t-Boc group was removed by incubating the sample at low temperature in the presence of acid to yield Cap-MLA. This product was analyzed by californium plasma desorption mass spectrometry (PDMS). Purified t-Boc-Cap-MLA was further fractionated by reverse-phase high-performance liquid chromatography as its methyl ester and characterized by laser desorption mass spectrometry, PDMS, and proton nuclear magnetic resonance spectroscopy. These analyses revealed that the Cap group was selectively introduced into the 6'-position of MLA. To demonstrate that Cap-MLA can be conjugated to other compounds, it was reacted with biotin-Cap N-hydroxysuccinimide ester to yield biotin-(Cap)2-MLA. Analysis of this product by PDMS confirmed its expected molecular weight of 2171 and showed the presence of fragments containing the biotin and Cap groups. Monoclonal antibodies and streptavidin were used to show the presence of both lipid A and biotin in this conjugated product. These two novel lipid A derivatives were then tested for their bioactivities. Although both Cap-MLA and biotin-(Cap)2-MLA showed mitogenic activity using murine splenocytes, they were about 4-8 times less active than MLA at 20 mug/mL or less and only one-half as active at 100 mug/mL. In the induction of tumor necrosis factor release by RAW 264.7 murine macrophage cell line, the biotin-(Cap)2-MLA showed 7-9-fold lower activity than MLA at the concentration range of 0.1-1.0 /mug/mL. These results showed that Cap-MLA is a biologically active lipid A derivative that can be conjugated to other compounds through its free amino group to form new and active derivatives. It should thus be a useful reagent to study the biological properties of lipid A. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MYCOBACTERIOL RES LAB,MADISON,WI 53705. UNIV WISCONSIN,COLL AGR & LIFE SCI,DEPT BACTERIOL,MADISON,WI 53706. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. RP MYERS, KR (reprint author), RIBI IMMUNOCHEM RES INC,553 OLD CORVALLIS RD,HAMILTON,MT 59840, USA. RI Wang, Rong/A-8721-2009 FU NCRR NIH HHS [RR-02301, RR02301, RR02781] NR 32 TC 6 Z9 6 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV-DEC PY 1992 VL 3 IS 6 BP 540 EP 548 DI 10.1021/bc00018a013 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA KA511 UT WOS:A1992KA51100013 PM 1463784 ER PT J AU RAVINDRANATH, Y ABELLA, E KRISCHER, JP WILEY, J INOUE, S HARRIS, M CHAUVENET, A ALVARADO, CS DUBOWY, R RITCHEY, AK LAND, V STEUBER, CP WEINSTEIN, H AF RAVINDRANATH, Y ABELLA, E KRISCHER, JP WILEY, J INOUE, S HARRIS, M CHAUVENET, A ALVARADO, CS DUBOWY, R RITCHEY, AK LAND, V STEUBER, CP WEINSTEIN, H TI ACUTE MYELOID-LEUKEMIA (AML) IN DOWNS-SYNDROME IS HIGHLY RESPONSIVE TO CHEMOTHERAPY - EXPERIENCE ON PEDIATRIC ONCOLOGY GROUP AML STUDY-8498 SO BLOOD LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; BRITISH COOPERATIVE GROUP; CANCER-STUDY-GROUP; POOR PROGNOSIS; CHILDREN; INTENSIFICATION; IDENTIFICATION; TRANSLOCATION C1 WAYNE STATE UNIV,CHILDRENS HOSP MICHIGAN,DETROIT,MI 48202. UNIV FLORIDA,PEDIAT ONCOL GRP,STAT OFF,GAINESVILLE,FL 32611. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. HURLEY MED CTR,FLINT,MI. HACKENSACK MED CTR,INST TOMORROWS CHILDRENS,HACKENSACK,NJ. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. EMORY UNIV,SCH MED,ATLANTA,GA 30322. SUNY HLTH SCI CTR,SYRACUSE,NY. W VIRGINIA UNIV,MED CTR,SCH MED,MORGANTOWN,WV 26506. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. BAYLOR COLL MED,HOUSTON,TX 77030. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA-28476, CA-29691, CA-29139] NR 43 TC 188 Z9 192 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 NOV 1 PY 1992 VL 80 IS 9 BP 2210 EP 2214 PG 5 WC Hematology SC Hematology GA JW436 UT WOS:A1992JW43600008 PM 1384797 ER PT J AU UCHIYAMA, H BARUT, BA CHAUHAN, D CANNISTRA, SA ANDERSON, KC AF UCHIYAMA, H BARUT, BA CHAUHAN, D CANNISTRA, SA ANDERSON, KC TI CHARACTERIZATION OF ADHESION MOLECULES ON HUMAN MYELOMA CELL-LINES SO BLOOD LA English DT Article ID PHORBOL ESTER TREATMENT; MONOCLONAL-ANTIBODY; PERIPHERAL-BLOOD; B-CELLS; FIBRONECTIN RECEPTORS; ANTIGEN-1 LFA-1; SURFACE-ANTIGEN; PRECURSOR CELLS; LYMPHOID-CELLS; IMMUNE-SYSTEM C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA50947] NR 58 TC 133 Z9 134 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1992 VL 80 IS 9 BP 2306 EP 2314 PG 9 WC Hematology SC Hematology GA JW436 UT WOS:A1992JW43600021 PM 1421401 ER PT J AU HARRIS, N SUPER, M RITS, M CHANG, G EZEKOWITZ, RAB AF HARRIS, N SUPER, M RITS, M CHANG, G EZEKOWITZ, RAB TI CHARACTERIZATION OF THE MURINE MACROPHAGE MANNOSE RECEPTOR - DEMONSTRATION THAT THE DOWN-REGULATION OF RECEPTOR EXPRESSION MEDIATED BY INTERFERON-GAMMA OCCURS AT THE LEVEL OF TRANSCRIPTION SO BLOOD LA English DT Article ID CARBOHYDRATE-RECOGNITION DOMAINS; BINDING-PROTEIN; LECTIN DOMAIN; CLONING; SEQUENCE; SYSTEM; CELLS; CHAIN; GENE; AMPLIFICATION C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP HARRIS, N (reprint author), CHILDRENS HOSP MED CTR,DIV HEMATOL ONCOL,ENDERS BLDG,7TH FLOOR,300 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [R01 AI23786-05] NR 48 TC 123 Z9 124 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 NOV 1 PY 1992 VL 80 IS 9 BP 2363 EP 2373 PG 11 WC Hematology SC Hematology GA JW436 UT WOS:A1992JW43600028 PM 1421407 ER PT J AU HANNA, E DUFOUR, MC ELLIOTT, S STINSON, F HARFORD, TC AF HANNA, E DUFOUR, MC ELLIOTT, S STINSON, F HARFORD, TC TI DYING TO BE EQUAL - WOMEN, ALCOHOL, AND CARDIOVASCULAR-DISEASE SO BRITISH JOURNAL OF ADDICTION LA English DT Note ID CONSUMPTION; MORTALITY; HEART; STROKE; RISK; MEN AB This data note explores the relationship of gender, alcohol consumption and premature cardiovascular disease (MCVD). Data on the 8164 deaths attributed to MCVD from the National Mortality Followback Study (NMFS) were analyzed controlling for gender and consumption. Women who are heavy drinkers die young at a rate equal to that of men who drink heavily. In light of this, we recommend that future research and preventive efforts in this area include females as subjects and alcohol as a major risk factor. C1 CSR INC,WASHINGTON,DC 20005. NIAAA,WASHINGTON,DC 20005. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP HANNA, E (reprint author), NIAAA,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20857, USA. NR 18 TC 16 Z9 16 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0952-0481 J9 BRIT J ADDICT PD NOV PY 1992 VL 87 IS 11 BP 1593 EP 1597 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA JX830 UT WOS:A1992JX83000010 PM 1458038 ER PT J AU BECH, P ALLERUP, P MAIER, W ALBUS, M LAVORI, P AYUSO, JL AF BECH, P ALLERUP, P MAIER, W ALBUS, M LAVORI, P AYUSO, JL TI INSIGHT AND ILLUSION SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Letter C1 DANISH INST EDUC RES,COPENHAGEN,DENMARK. UNIV MAINZ,DEPT PSYCHIAT,W-6500 MAINZ,GERMANY. UNIV MUNICH,PSYCHIAT CLIN,W-8000 MUNICH 2,GERMANY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV MADRID,MADRID 3,SPAIN. RP BECH, P (reprint author), FREDERIKSBORG CENT CTY HOSP,DEPT PSYCHIAT,DK-3400 HILLEROD,DENMARK. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD NOV PY 1992 VL 161 BP 716 EP 717 PG 2 WC Psychiatry SC Psychiatry GA JY239 UT WOS:A1992JY23900034 PM 1422631 ER PT J AU BLANKENSTEIJN, JD AF BLANKENSTEIJN, JD TI PYLORUS-PRESERVING VERSUS STANDARD PANCREATICODUODENECTOMY - AN ANALYSIS OF 110 PANCREATIC AND PERIAMPULLARY CARCINOMAS SO BRITISH JOURNAL OF SURGERY LA English DT Letter RP BLANKENSTEIJN, JD (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. RI Blankensteijn, Jan/Q-9291-2016 OI Blankensteijn, Jan/0000-0002-2062-8749 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD NOV PY 1992 VL 79 IS 11 BP 1249 EP 1249 DI 10.1002/bjs.1800791153 PG 1 WC Surgery SC Surgery GA JY105 UT WOS:A1992JY10500052 PM 1361405 ER PT J AU UNENO, S YAMAMURO, T JUPPNER, H ABOUSAMRA, AB KEUTMANN, HT POTTS, JT SEGRE, GV AF UNENO, S YAMAMURO, T JUPPNER, H ABOUSAMRA, AB KEUTMANN, HT POTTS, JT SEGRE, GV TI SOLUBILIZATION OF FUNCTIONAL RECEPTORS FOR PARATHYROID-HORMONE AND PARATHYROID HORMONE-RELATED PEPTIDE FROM CLONAL RAT OSTEOSARCOMA CELLS, ROS17/2.8 SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE PARATHYROID HORMONE; PTH-RELATED PEPTIDE; RECEPTORS; SOLUBILIZATION; ROS17/2.8 CELLS ID CANINE RENAL CORTEX; HUMORAL HYPERCALCEMIA; HIGH-AFFINITY; PLASMA-MEMBRANES; MALIGNANCY; ANALOG; IDENTIFICATION; BINDING; AGONIST AB ROS17/2.8 cells, a cell line derived from a rat osteosarcoma, have abundant receptors for parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP). A particulate membrane fraction was prepared from these cells and it was solubilized using relatively mild conditions with digitonin (0.25%), a nonionic detergent. When radioligands of both PTH and PTHrP were incubated with this membrane fraction in the absence of any protease inhibitor at 15-degrees-C, approximately 75% of these radioligands were degraded within 2 hours. This degradative activity was inhibited more effectively by bacitracin than by any of several other protease inhibitors tested. The digitonin-solubilized PTH/PTHrP receptors were radiolabeled in the presence of bacitracin using radioiodinated [Tyr36]PTHrP(1-36) amide (PTHrP(1-36)) and N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), as cross-linker. When an aliquot of the reaction solution was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and autoradiography, a broad band was observed that had an apparent molecular size of 90,000 daltons (M(r) = 90 kD). This band was no longer seen when the binding was conducted in the presence of 10(-6) M of unlabeled PTHrP(1-36), and it was decreased in density when binding was conducted in the presence of 10(-6) M of unlabeled [Nle8,18, Tyr34] bovine PTH(1-34) amide (NlePTH). The solubilized receptors retained their capacity to bind the radioligand after partial purification by wheat-germ agglutinin affinity-chromatography. The use of relatively mild detergent conditions thus offers a means to solubilize receptors that retain their capacity to bind PTH and PTHrP. C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. KYOTO UNIV,FAC MED,DEPT ORTHOPAED SURG,KYOTO 606,JAPAN. OI Abou-Samra, Abdul/0000-0001-8735-1142 NR 27 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD NOV PY 1992 VL 51 IS 5 BP 382 EP 386 DI 10.1007/BF00316884 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JU767 UT WOS:A1992JU76700010 PM 1333876 ER PT J AU HUNCHAREK, M AF HUNCHAREK, M TI CHANGING RISK GROUPS FOR MALIGNANT MESOTHELIOMA - REPLY SO CANCER LA English DT Letter RP HUNCHAREK, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 8 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 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1992 VL 70 IS 9 BP 2379 EP 2380 PG 2 WC Oncology SC Oncology GA JU762 UT WOS:A1992JU76200029 ER PT J AU WINN, DM LI, FP ROBISON, LL MULVIHILL, JJ DAIGLE, AE FRAUMENI, JF AF WINN, DM LI, FP ROBISON, LL MULVIHILL, JJ DAIGLE, AE FRAUMENI, JF TI A CASE-CONTROL STUDY OF THE ETIOLOGY OF EWING SARCOMA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHILDHOOD-CANCER IRESCC; MULTIMODAL THERAPY; CONTROL SELECTION; MATERNAL SMOKING; NEURO-BLASTOMA; BIRTH-DEFECTS; BRAIN-TUMORS; BONE CANCER; CHILDREN; RISK AB An interview case-control study was undertaken to search for risk factors for Ewing's sarcoma. The 208 cases, aged 5 months to 22 years at diagnosis and all white but one, were identified from hospitals participating in the intergroup Ewing's Sarcoma Study therapeutic trials. Two controls were sought for each case: a sibling control and an age-matched regional population control identified through random-digit dialing telephone procedures. A questionnaire was administered to the parents of cases and controls. Parents were more likely to have smoked during the pregnancy with the case than during the pregnancy with the unaffected sibling. Risks rose with the number of cigarettes the mother smoked per day during the pregnancy. Concepti exposed to less than 1 pack/day were at 3.2 times the risk, and those exposed to 1 pack or more were at 6.7 times the risk of the nonexposed. However, risks associated with smoking were lower and not statistically significant in analyses using the region-matched controls. Hernias, mostly umbilical and inguinal, were diagnosed six times more frequently among the cases compared to region-matched controls. However, hernias occurred in just 10% of cases, and the matched siblings had hernias diagnosed with the same frequency as the cases. An apparent excess of heart disorders among cases versus siblings seems likely to be an artifact of increased medical surveillance of cases. Fathers of Ewing's sarcoma cases were 2 times more likely to work as farmers at the time of conception than fathers of region-matched controls and 3 times more likely to have farming as their usual occupation, but the findings did not reach statistical significance. Ewing's sarcoma was not linked to other factors which were examined: antecedent bone trauma-cancer among relatives; demographic characteristics including religion, education, and income; and anthropomorphic measures (child's birth height or weight or parents' height or weight). Although a wide range of demographic, maternal reproductive, child health, occupational, and family history data were obtained, Ewing's sarcoma remains a cancer of unknown cause. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV PITTSBURGH,PITTSBURGH,PA 15260. IMMUNE RESPONSE CORP,CARLSBAD,CA. NCI,BETHESDA,MD 20892. RP WINN, DM (reprint author), CTR DIS CONTROL,NATL CTR HLTH STAT,DIV HLTH INTERVIEW STAT,6525 BELCREST RD,ROOM 850,HYATTSVILLE,MD 20782, USA. NR 55 TC 33 Z9 35 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV-DEC PY 1992 VL 1 IS 7 BP 525 EP 532 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JY264 UT WOS:A1992JY26400001 PM 1302564 ER PT J AU CAGGANA, M LIBER, HL COLEMAN, CN MAUCH, P CLARK, JR KELSEY, KT AF CAGGANA, M LIBER, HL COLEMAN, CN MAUCH, P CLARK, JR KELSEY, KT TI A PROSPECTIVE-STUDY OF HPRT MUTANT AND MUTATION FREQUENCIES IN TREATED CANCER-PATIENTS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN LYMPHOCYTES-T; OXIDE-EXPOSED PRIMATES; HUMAN PERIPHERAL-BLOOD; 6-THIOGUANINE-RESISTANT LYMPHOCYTES; MOLECULAR ANALYSES; CLONING ASSAY; CIRCULATING LYMPHOCYTES; HODGKINS-DISEASE; CELL CLONING; INVIVO AB We previously reported that some Hodgkin's disease patients had elevated hprt mutant frequencies in peripheral blood lymphocytes long after cessation of therapy. To determine if these elevations in mutant frequency represent true persistently elevated mutation frequencies, we recruited for a prospective study six previously treated Hodgkin's disease patients and five patients who had been treated for squamous cell carcinoma of the head and neck. These individuals were studied several times over a 6-7-month period. The results confirmed that a subset of patients have persistently high mutant frequencies when compared to 71 previously studied controls. The present study was designed to determine if the elevated mutant frequencies of treated patients represented independent mutations or resulted from the in vivo expansion of single mutant cells. We used the polymerase chain reaction to examine DNA single-strand conformation polymorphisms at the T-cell receptor gamma locus of individual mutant clones. This analysis showed that at any given time 20.1% of the mutants from Hodgkin's disease patients and 17.5% of the mutants from squamous cell carcinoma patients consisted of siblings, identified as having identical polymerase chain reaction/single-stranded conformation polymorphism patterns. The remaining mutants had unique polymerase chain reaction/single-stranded conformation polymorphism patterns and therefore can be presumed to have arisen from independent mutational events. Particular sibling mutants generally did not persist over time. However, one patient had one mutant clone which persisted but slowly decreased in prevalence over a 7-month sampling period. The data demonstrate that treatments for cancer result in persistently elevated mutation frequencies at the hprt locus in some, but not all, patients. In addition, our results confirm previous studies indicating that it is not always appropriate to assume equality between mutant and mutation frequencies when studying individuals exposed to significant doses of known mutagens or carcinogens. C1 HARVARD UNIV,SCH PUBL HLTH,RADIOBIOL LAB,665 HUNTINGTON AVE,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RI Kelsey, Karl/I-1252-2014 FU NCI NIH HHS [CA09078]; NIEHS NIH HHS [ES-00002] NR 29 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV-DEC PY 1992 VL 1 IS 7 BP 573 EP 580 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JY264 UT WOS:A1992JY26400010 PM 1302570 ER PT J AU ESKEY, CJ KORETSKY, AP DOMACH, MM JAIN, RK AF ESKEY, CJ KORETSKY, AP DOMACH, MM JAIN, RK TI H-2-NUCLEAR MAGNETIC-RESONANCE-IMAGING OF TUMOR BLOOD-FLOW - SPATIAL AND TEMPORAL HETEROGENEITY IN A TISSUE-ISOLATED MAMMARY ADENOCARCINOMA SO CANCER RESEARCH LA English DT Article ID PERFUSION; SPECTROSCOPY; TRACER; BRAIN; CARCINOMA; HYPOXIA; INVIVO; MODELS; MICE AB H-2-Nuclear magnetic resonance imaging of deuteron accumulation in tissue following an i.v. bolus of deuterium oxide provides a noninvasive means of constructing maps of tissue perfusion. With a measured arterial input function and a simple model for tissue-capillary exchange, these data can provide quantitative estimates of local flow. This technique was tested in rat brain and then applied to the study of spatial heterogeneity and temporal variation of blood flow in the tissue-isolated R3230AC mammary adenocarcinoma. Global flow from the brain averaged 0.96 ml/min.g, in good agreement with results obtained from other methods; the perfusion of brain was relatively homogeneous. Global tumor blood flow averaged 0.32 ml/min.g, ranging from 0.11 to 0.96 ml/min.g. Imaging revealed variations in perfusion both within and between the tumors that far exceeded those expected from brain flow heterogeneity and uncertainty in the flow estimates. By obtaining repeated flow images at 30-min intervals, it was possible to show that the regional blood flow shifted with time in single pixels and in multipixel regions. These experiments show that H-2-nuclear magnetic resonance may be useful in obtaining noninvasive and quantitative measurement of temporal blood flow changes in a solid tumor in vivo. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114. CARNEGIE MELLON UNIV,PITTSBURGH NMR CTR BIOMED RES,PITTSBURGH,PA 15213. CARNEGIE MELLON UNIV,DEPT CHEM ENGN,PITTSBURGH,PA 15213. CARNEGIE MELLON UNIV,DEPT BIOL SCI,PITTSBURGH,PA 15213. RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU NCI NIH HHS [CA37239]; NCRR NIH HHS [1 P41 RR03631] NR 33 TC 70 Z9 72 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 NOV 1 PY 1992 VL 52 IS 21 BP 6010 EP 6019 PG 10 WC Oncology SC Oncology GA JV496 UT WOS:A1992JV49600023 PM 1394226 ER PT J AU HUFF, V REEVE, AE LEPPERT, M STRONG, LC DOUGLASS, EC GEISER, CF LI, FP MEADOWS, A CALLEN, DF LENOIR, G SAUNDERS, GF AF HUFF, V REEVE, AE LEPPERT, M STRONG, LC DOUGLASS, EC GEISER, CF LI, FP MEADOWS, A CALLEN, DF LENOIR, G SAUNDERS, GF TI NONLINKAGE OF 16Q MARKERS TO FAMILIAL PREDISPOSITION TO WILMS-TUMOR SO CANCER RESEARCH LA English DT Note ID GENE; CHROMOSOME-11; DELETION; 11P13; RECOMBINATION; POLYMORPHISMS; MUTATIONS; LINKAGE; LOCUS AB Wilms' tumor (WT), a childhood cancer of the kidney, occurs in both familial and sporadic forms. Chromosome 11 genes have been implicated in the etiology of WT1, and mutations in a gene at chromosomal band 11p13, WT1, have been identified in a few WT cases. However, 11p13 has been excluded as the site of the predisposition mutation segregating in several large WT families, which implies the existence of a non-11p familial predisposition gene. Recently, loss of heterozygosity for 16q markers located between chromosomal bands 16q13 and 16q22 has been reported in approximately 20% of sporadic Wilms' tumors. To determine if this region of 16q harbors the non-11p familial WT gene, a genetic linkage study of five WT families was undertaken. Using multipoint analyses, we ruled out genetic linkage of familial WT predisposition to 16q. C1 ADELAIDE CHILDRENS HOSP INC, DEPT CYTOGENET & MOLEC GENET, ADELAIDE, SA 5006, AUSTRALIA. CHILDRENS HOSP PHILADELPHIA, DIV ONCOL, PHILADELPHIA, PA 19104 USA. UNIV TEXAS, MD ANDERSON CANC CTR, DEPT EXPTL PEDIAT, HOUSTON, TX 77030 USA. UNIV OTAGO, DEPT BIOCHEM, MOLEC CARCINOGENESIS LAB, DUNEDIN, NEW ZEALAND. UNIV UTAH, MED CTR, HOWARD HUGHES MED INST, SALT LAKE CITY, UT 84132 USA. ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38101 USA. UNIV TEXAS, HLTH SCI CTR, DEPT PEDIAT, DIV HEMATOL ONCOL, SAN ANTONIO, TX 78284 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH PUBL HLTH, BOSTON, MA 02115 USA. INT AGCY RES CANC, F-69372 LYON, FRANCE. RP HUFF, V (reprint author), UNIV TEXAS, MD ANDERSON CANC CTR, DEPT BIOCHEM & MOLEC BIOL, BOX 117, HOUSTON, TX 77030 USA. RI Callen, David/G-1975-2012; OI Callen, David/0000-0002-6189-9991 NR 20 TC 67 Z9 67 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1992 VL 52 IS 21 BP 6117 EP 6120 PG 4 WC Oncology SC Oncology GA JV496 UT WOS:A1992JV49600042 PM 1356625 ER PT J AU MORRISON, DA BARBIERE, CC JOHNSON, R MARSHALL, G FULLERTON, D HAMMERMEISTER, KE GROVER, FL AF MORRISON, DA BARBIERE, CC JOHNSON, R MARSHALL, G FULLERTON, D HAMMERMEISTER, KE GROVER, FL TI SALVAGE ANGIOPLASTY - AN ALTERNATIVE TO HIGH-RISK SURGERY FOR UNSTABLE ANGINA SO CATHETERIZATION AND CARDIOVASCULAR DIAGNOSIS LA English DT Article DE ANGIOPLASTY; CORONARY ARTERY DISEASE; CORONARY ARTERY BYPASS ID LUMINAL CORONARY ANGIOPLASTY; MYOCARDIAL-INFARCTION; ARTERY DISEASE; BALLOON COUNTERPULSATION; SURGICAL-TREATMENT; MEDICAL THERAPY; BYPASS-SURGERY; PECTORIS; MANAGEMENT; REGISTRY AB This prospective, Human Subjects Committee and Ethics Committee approved investigation was performed to determine if coronary angioplasty (PTCA) might be a reasonable alternative revascularization method for unstable angina patients thought to be at high risk for operative (CABG) mortality. Between March 1990 and October 1991, thirty-four consecutive patients with medically refractory rest angina were deamed to have high risk of surgical mortality and underwent PTCA without surgical backup. Predicted operative mortality was calculated for each patient based upon the VA Surgical Risk Assessment model. Angioplasty of 52 vessels was attempted. Reduction in lumenal narrowing to < 50% and improved angiographic flow was obtained in 47 vessels. There were four complicating infarctions. One death occurred in the lab, and three patients with unsuccessful angioplasty died within 30 days of pump failure. Relief of angina occurred in 30/34. Thirty patients were discharged home. In follow-up from 1 to 12 months, there have been 2 late sudden deaths at 4 months and 9 months, 1 death from lung cancer; 4 patients have stable exertional angina; 2 are awaiting heart transplant but are pain free, and one patient who had PTCA during cardiogenic shock from acute myocardial infarction had elective coronary artery bypass surgery. There have been no late myocardial infarctions. The observed angioplasty 30-day mortality of 11.8% (95% confidence limit 1% to 22.6%) compares favorably with the predicted operative mortality of 23.8% for this group. This prospective but non-randomized series supports the concept that balloon angioplasty may be a reasonable alternative to surgical intervention in some patients with unstable angina and high risk for surgery. A prospective randomized trial is warranted. C1 DENVER VET AFFAIRS MED CTR,CARDIOL SERV,DENVER,CO. DENVER VET AFFAIRS MED CTR,CARDIAC SURG SERV,DENVER,CO. UNIV COLORADO,HLTH SCI CTR,DENVER,CO 80262. RI Marshall, Guillermo/F-2302-2011 NR 43 TC 19 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0098-6569 J9 CATHETER CARDIO DIAG JI Catheter. Cardiovasc. Diagn. PD NOV PY 1992 VL 27 IS 3 BP 169 EP 178 DI 10.1002/ccd.1810270304 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JV349 UT WOS:A1992JV34900003 PM 1423571 ER PT J AU TORIMOTO, Y DANG, NH STREULI, M ROTHSTEIN, DM SAITO, H SCHLOSSMAN, SF MORIMOTO, C AF TORIMOTO, Y DANG, NH STREULI, M ROTHSTEIN, DM SAITO, H SCHLOSSMAN, SF MORIMOTO, C TI ACTIVATION OF T-CELLS THROUGH A T-CELL-SPECIFIC EPITOPE OF CD45 SO CELLULAR IMMUNOLOGY LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; THYMIC GENERATIVE LINEAGE; MIXED LYMPHOCYTE-REACTION; MONOCLONAL-ANTIBODIES; TYROSINE PHOSPHATASE; RECEPTOR COMPLEX; 2H4 MOLECULE; DIFFERENTIATION ANTIGENS; FUNCTIONAL-HETEROGENEITY; ALTERNATIVE PATHWAY C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. FU NIAID NIH HHS [AI-29530, AI-12069]; NIAMS NIH HHS [AR-33713] NR 73 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV PY 1992 VL 145 IS 1 BP 111 EP 129 DI 10.1016/0008-8749(92)90317-I PG 19 WC Cell Biology; Immunology SC Cell Biology; Immunology GA JX878 UT WOS:A1992JX87800011 PM 1384991 ER PT J AU KUNTZ, RE RUSKIN, JN WEINBERGER, S LORELL, BH AF KUNTZ, RE RUSKIN, JN WEINBERGER, S LORELL, BH TI THE ADVANTAGE OF D-SOTALOL OVER DL-SOTALOL IN A PATIENT WITH VENTRICULAR ARRHYTHMIAS AND COMORBID BRONCHOSPASM SO CHEST LA English DT Article AB The anti-arrhythmic agent sotalol, a racemic mixture of d- and l-isomers, has inherent beta-adrenoreceptor blocking activity due to the l-isomer form. For patients with contraindications to beta-adrenoreceptor blockade, dl-sotalol has potentially untoward effects that may limit its usefulness. The case of a man with resistant life-threatening ventricular arrhythmias who responded favorably to dl-sotalol, but developed worsening of underlying bronchospastic lung disease, is presented. A change in therapy to the d-isomer form of sotalol, d-sotalol, was effective in suppressing his ventricular arrhythmias without further aggravation of bronchospasm. C1 BETH ISRAEL HOSP,THORNDIKE LAB,DEPT MED,DIV CARDIOVASC,BOSTON,MA 02215. BETH ISRAEL HOSP,THORNDIKE LAB,DEPT MED,DIV PULM,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114. RP KUNTZ, RE (reprint author), BETH ISRAEL HOSP,CHARLES A DANA RES INST,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 10 TC 2 Z9 2 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD NOV PY 1992 VL 102 IS 5 BP 1627 EP 1629 DI 10.1378/chest.102.5.1627 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA JX209 UT WOS:A1992JX20900083 PM 1424914 ER PT J AU ISHIHARA, K ZILE, MR KANAZAWA, S TSUTSUI, H URABE, Y DEFREYTE, G CARABELLO, BA AF ISHIHARA, K ZILE, MR KANAZAWA, S TSUTSUI, H URABE, Y DEFREYTE, G CARABELLO, BA TI LEFT-VENTRICULAR MECHANICS AND MYOCYTE FUNCTION AFTER CORRECTION OF EXPERIMENTAL CHRONIC MITRAL REGURGITATION BY COMBINED MITRAL-VALVE REPLACEMENT AND PRESERVATION OF THE NATIVE MITRAL-VALVE APPARATUS SO CIRCULATION LA English DT Article DE CONTRACTILITY; VALVULAR HEART DISEASE ID EXPERIMENTAL VOLUME OVERLOAD; WALL STRESS; CONTRACTILE FUNCTION; CHORDAE TENDINEAE; CARDIAC-MUSCLE; REGIONAL WORK; PERFORMANCE; STIFFNESS; LOGARITHM; THICKNESS AB Background. Contractile function improves after correction of experimental mitral regurgitation, but ejection performance becomes depressed when mitral valve replacement involves chordal transection. A role for chordal transection in producing the depressed ejection performance was suspected but uncertain. Therefore, in this study, we tested two specific hypotheses: 1) that contractile function would improve and, in conjunction with chordal preservation, would allow for preserved ejection performance and 2) that improved left ventricular contractile function after surgery would be reflected in the function of myocytes isolated from the affected left ventricles. Methods and Results. We examined ventricular contractile function and ejection performance and isolated myocyte function after correction of experimental mitral regurgitation (chordal rupture) with mitral valve replacement that involved chordal preservation. After 3 months of chronic mitral regurgitation, the average regurgitant fraction of seven dogs was 0.77+/-0.04. End-diastolic volume had increased from 79+/-5 to 132+/-10 cm3 (p < 0.05). At that time, all indexes of left ventricular contractile function were depressed. Three months after mitral valve replacement with chordal preservation, end-diastolic volume fell to 100+/-4 cm3 (p < 0.05). At this time, all indexes of contractile function had returned to normal. End-systolic stress and ejection fraction after mitral valve replacement were similar to their baseline levels. Viscosity-velocity curves (analogous to force-velocity curves) of myocytes isolated from the affected left ventricles were similar to those of myocytes isolated from normal left ventricles. Conclusions. We conclude that mitral valve replacement with chordal preservation allows ventricular contractile function to return to normal. Normal global ventricular function, in turn, is associated with normal function of the individual myocytes that compose the left ventricular chamber. Further, chordal preservation allowed for loading and ejection performance to return to premorbid levels. C1 MED UNIV S CAROLINA,DEPT MED,DIV CARDIOL,171 ASHLEY AVE,CHARLESTON,SC 29425. MED UNIV S CAROLINA,GAZES CARDIAC RES INST,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS,CARDIOL SECT,CHARLESTON,SC. RI Tsutsui, Hiroyuki/A-4070-2012 NR 43 TC 27 Z9 27 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1992 VL 86 IS 5 SU S BP 16 EP 25 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JX589 UT WOS:A1992JX58900003 ER PT J AU PEARLMAN, JD MOORE, JR LIZAK, MJ AF PEARLMAN, JD MOORE, JR LIZAK, MJ TI REAL-TIME NMR BEAM-DIRECTED VELOCITY MAPPING - V-MODE NMR SO CIRCULATION LA English DT Article DE BLOOD FLOW; MAGNETIC RESONANCE IMAGING; REAL TIME; PULSE SEQUENCE ID BLOOD-FLOW; DOPPLER US; MR; CARDIOGRAPHY; ANGIOGRAPHY AB Background. Currently available noninvasive techniques for measuring blood flow velocities are constrained by limited view orientations (Doppler ultrasound) or limited time resolution (magnetic resonance imaging, MRI). We describe an MRI technique for measuring flow velocities in real time at arbitrary orientations within a cylindrical volume or "beam": V-mode nuclear magnetic resonance (NMR). Methods and Results. The technique was implemented on a standard 1.5-T clinical NMR imager with no special hardware and was tested on phantoms and human volunteers. The beam can be fired at rates up to 60 times per second, allowing measurements on a time scale that is appropriate for ungated cardiac studies. In phantoms, steady flow velocities were measured with the beam aligned along the direction of flow, and the measured velocities correlated well with the actual velocities (r>0.99). The radial distribution of velocities in phantoms under constant flow conditions was also determined. In humans, flow of blood in the descending aortas of normal and aortic insufficiency subjects was measured. Distinctive backflow of blood because of aortic insufficiency was readily apparent. Conclusions. The V-mode NMR technique is capable of acquiring clinically relevant real-time blood flow information from any desired angle of view with no attenuation at bone or air-tissue interfaces. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. RP PEARLMAN, JD (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA 02215, USA. FU NCI NIH HHS [5T32CA09362-08] NR 17 TC 10 Z9 10 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV PY 1992 VL 86 IS 5 BP 1433 EP 1438 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA JW981 UT WOS:A1992JW98100012 PM 1423957 ER PT J AU LEWANDROWSKI, K LEELEWANDROWSKI, E BOWERS, GN MCCOMB, RB AF LEWANDROWSKI, K LEELEWANDROWSKI, E BOWERS, GN MCCOMB, RB TI INVESTIGATION OF N-METHYL-D-GLUCAMINE BUFFER FOR ASSAY OF ALKALINE-PHOSPHATASE IN SERUM SO CLINICAL CHEMISTRY LA English DT Note AB We evaluated N-methyl-D-glucamine (MEG) as a buffer for assay of alkaline phosphatase (ALP; EC 3.1.3.1) and compared the MEG-based assay with the current International Federation of Clinical Chemistry Reference method for ALP (IFCC/RM/ALP), in which 2-amino-2-methyl-1-propanol (AMP) is the pH buffer. The ALP assay in MEG at 30 and 37-degrees-C shows excellent correlation with the IFCC/RM/ALP at 30-degrees-C, but yields proportionately higher ALP activities (8.2% at 30-degrees-C and 57% at 37-degrees-C). ALP is unstable in both MEG and AMP at 37-degrees-C. Serum incubated in MEG undergoes a pH-dependent biphasic loss of ALP activity: an initial rapid 5% loss after 1 min of incubation and a 10% loss per hour thereafter. A similar pattern was seen for incubation with AMP. The use of a serum-initiated reaction (no preincubation of enzyme with buffer) eliminated the early loss in activity. The addition of the metal ion buffer N-hydroxyethylethylenediaminetriacetic acid, along with low concentrations of Zn and Mg, as used in the IFCC/RM/ALP, reduced the slow loss in activity over time, as did decreasing the reaction temperature to 30-degrees-C, but had no effect on the early rapid decay in activity seen in the first minute. Moderate transphosphorylation (45%) and nonenzymatic hydrolysis (3.3 U/L) were observed with MEG under the conditions of the assay (37-degrees-C). A comparison of different lots of MEG from two manufacturers showed no significant difference in ALP activities. C1 HARTFORD HOSP,CLIN CHEM LAB,HARTFORD,CT 06115. MASSACHUSETTS GEN HOSP,DEPT PATHOL & CLIN CHEM,BOSTON,MA 02114. NR 18 TC 5 Z9 6 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 1992 VL 38 IS 11 BP 2286 EP 2294 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA JY304 UT WOS:A1992JY30400024 PM 1424126 ER PT J AU ANAISSIE, E GOKASLAN, A HACHEM, R RUBIN, R GRIFFIN, G ROBINSON, R SOBEL, J BODEY, G AF ANAISSIE, E GOKASLAN, A HACHEM, R RUBIN, R GRIFFIN, G ROBINSON, R SOBEL, J BODEY, G TI AZOLE THERAPY FOR TRICHOSPORONOSIS - CLINICAL-EVALUATION OF 8 PATIENTS, EXPERIMENTAL-THERAPY FOR MURINE INFECTION, AND REVIEW SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BEIGELII CUTANEUM INFECTION; INTRAVENOUS DRUG-ABUSE; AMPHOTERICIN-B; BLASTOSCHIZOMYCES-CAPITATUS; IMMUNOSUPPRESSED HOST; SYSTEMIC INFECTION; ACUTE-LEUKEMIA; ENDOCARDITIS; TRANSPLANTATION; INVOLVEMENT AB We studied the in vivo antifungal activity of azoles in humans and in a murine model of disseminated trichosporonosis. Eight patients infected with Trichosporon species were treated with fluconazole, SCH 39304, or miconazole for 2-26 weeks. Four patients had fungemia, two patients had disseminated trichosporonosis, and one patient each had soft-tissue infection and cystitis. Response of trichosporonosis to azoles was seen in all eight patients, although one patient died with disseminated aspergillosis while still receiving SCH 39304. A literature review indicated that responses to ketoconazole or miconazole were noted in four patients with trichosporonosis. In the experimental infection, amphotericin B, SCH 39304, and fluconazole were effective in prolonging survival and reducing fungal counts in the kidneys of mice infected with a clinical strain of Trichosporon beigelii. Fluconazole but not amphotericin B prolonged survival of mice infected with a clinical strain of Trichosporon capitatum. We conclude that azoles represent effective therapy for infection with Trichosporon species. C1 MASSACHUSETTS GEN HOSP,INFECT DIS TRANSPLANTAT SECT,BOSTON,MA 02114. UNIV CALIF DAVIS,SACRAMENTO MED CTR,MED CTR,DEPT PEDIAT,SACRAMENTO,CA 95817. WAYNE STATE UNIV,SCH MED,DEPT INTERNAL MED,DIV INFECT DIS,DETROIT,MI 48201. RP ANAISSIE, E (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT MED SPECIALTIES,INFECT DIS SECT,BOX 47,HOUSTON,TX 77030, USA. NR 37 TC 90 Z9 92 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1992 VL 15 IS 5 BP 781 EP 787 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JX339 UT WOS:A1992JX33900005 PM 1445976 ER PT J AU HAFT, RF SHAPIRO, CL GANTZ, NM CHRISTENSON, JC WALLACE, RJ AF HAFT, RF SHAPIRO, CL GANTZ, NM CHRISTENSON, JC WALLACE, RJ TI PSEUDOINFECTION DUE TO TSUKAMURELLA-PAUROMETABOLUM SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CLIN ONCOL,BOSTON,MA 02115. POLYCLIN MED CTR,DEPT MED,HARRISBURG,PA. UNIV UTAH,DIV PEDIAT INFECT DIS,SALT LAKE CITY,UT 84112. UNIV TEXAS,HLTH SCI CTR,DEPT MICROBIOL,TYLER,TX. RP HAFT, RF (reprint author), BRIGHAM & WOMENS HOSP,DIV INFECT DIS,BOSTON,MA 02189, USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1992 VL 15 IS 5 BP 883 EP 883 PG 1 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JX339 UT WOS:A1992JX33900021 PM 1445990 ER PT J AU RUBIN, RH SHAPIRO, ED ANDRIOLE, VT DAVIS, RJ STAMM, WE AF RUBIN, RH SHAPIRO, ED ANDRIOLE, VT DAVIS, RJ STAMM, WE TI EVALUATION OF NEW ANTIINFECTIVE DRUGS FOR THE TREATMENT OF URINARY-TRACT INFECTION SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DOSE AMOXICILLIN THERAPY; TRIMETHOPRIM-SULFAMETHOXAZOLE; RANDOMIZED TRIAL; ACUTE DYSURIA; WOMEN; MANAGEMENT; BACTERIURIA; CHILDREN; INFANTS; PROPHYLAXIS AB The term urinary tract infection (UTI) encompasses a broad range of clinical entities that share one characteristic: a positive urine culture. Clinical manifestations and responses to therapy are diverse even when comparable numbers of a particular bacterial species are identified on urine culture. These guidelines include discussion of acute uncomplicated cystitis, acute uncomplicated pyelonephritis, and complicated infections of the urinary tract. It is proposed that the finding of greater-than-or-equal-to 10(3) cfu/mL of urine defines significant bacteriuria in acute uncomplicated cystitis, greater-than-or-equal-to 10(4) cfu/mL in acute uncomplicated pyelonephritis and UTI in men, and greater-than-or-equal-to 10(5) cfu/mL in complicated UTI. The preferred clinical study design is prospective, randomized, and controlled with an active agent. Ideally, treatment with antimicrobial agents should eradicate the infecting organism, bring about the resolution of clinical signs and symptoms, have few adverse effects, and prevent reinfection. C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. YALE NEW HAVEN MED CTR,CTR PRIMARY CARE,NEW HAVEN,CT 06504. YALE UNIV,SCH MED,DEPT MED,NEW HAVEN,CT 06510. UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT MED,SEATTLE,WA 98104. PHARMACO DYNAM RES INC,AUSTIN,TX. FU AHRQ HHS [HHS 223-88-1301] NR 36 TC 148 Z9 153 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV PY 1992 VL 15 SU 1 BP S216 EP S227 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JX586 UT WOS:A1992JX58600028 PM 1477233 ER PT J AU MURPHY, JM ARNETT, HL BISHOP, SJ JELLINEK, MS REEDE, JY AF MURPHY, JM ARNETT, HL BISHOP, SJ JELLINEK, MS REEDE, JY TI SCREENING FOR PSYCHOSOCIAL DYSFUNCTION IN PEDIATRIC PRACTICE - A NATURALISTIC STUDY OF THE PEDIATRIC SYMPTOM CHECKLIST SO CLINICAL PEDIATRICS LA English DT Article ID PRIMARY CARE; CHILDREN; DISORDERS; PSYCHOPATHOLOGY; PREVALENCE; VALIDATION; SCHOOL AB This study examined the routine implementation of the Pediatric Symptom Checklist (PSC), a brief questionnaire which screens for psychosocial dysfunction in school-aged children in an outpatient pediatric practice. Results indicated that the PSC was well-accepted by parents and adequately tolerated by busy clinic staff. When the PSC was included as part of the standard procedure for well-child visits, the referral rate for psychosocial problems due to positive PSC scores rose to 12% from the clinic baseline referral rate of 1.5%, a significant increase (P<.01). Half of the children who screened positive on the PSC had not been previously identified by their pediatricians as having psychosocial problems, and more than half had never received any psychological treatment. When implementation of the PSC was discontinued, the referral rate fell to 2%, a rate similar to baseline. The findings suggest that it is possible to incorporate the PSC into routine pediatric practice and that the PSC can help pediatricians identify and better serve children experiencing psychosocial difficulties. The study also suggests that further work is needed to understand the barriers to ongoing implementation. C1 MATTAPAN COMMUNITY HLTH CTR,MATTAPAN,MA. TUFTS UNIV,ELIOT PEARSON SCH APPL CHILD DEV,MEDFORD,MA 02155. RP MURPHY, JM (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,ACC 725,BOSTON,MA 02114, USA. NR 19 TC 43 Z9 44 U1 2 U2 4 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD NOV PY 1992 VL 31 IS 11 BP 660 EP 667 DI 10.1177/000992289203101104 PG 8 WC Pediatrics SC Pediatrics GA JY736 UT WOS:A1992JY73600004 PM 1424394 ER PT J AU CHEN, JF ELSNER, AE BURNS, SA HANSEN, RM LOU, PL KWONG, KK FULTON, AB AF CHEN, JF ELSNER, AE BURNS, SA HANSEN, RM LOU, PL KWONG, KK FULTON, AB TI THE EFFECT OF EYE SHAPE ON RETINAL RESPONSES SO CLINICAL VISION SCIENCES LA English DT Article DE MYOPIA; HYPEROPIA; A-SCAN ULTRASONOGRAPHY; MAGNETIC RESONANCE IMAGING; ELECTRORETINOGRAM; SCANNING LASER OPHTHALMOSCOPE AB 1. We investigated the size and shape of myopic eyes, and emmetropic and hyperopic control eyes, using refraction, ultrasonography, magnetic resonance imaging and scanning laser ophthalmoscope (SLO) imaging. 2. We measured full-field, scotopic sensitivities and saturated amplitudes of b-wave responses from these eyes. 3. The subjects' photopic psychophysical thresholds were measured at the posterior pole. 4. We find that saturated response amplitudes, but not sensitivities, are low in myopic subjects. 5. The psychophysical sensitivities are largely unaffected. 6. Eye shape is a better predictor of saturated response amplitude than eye size. 7. These results can be explained by low retinal cell responsivity, but not by increased spacing of retinal cells that would cause low sensitivity. C1 MASSACHUSETTS GEN HOSP,CTR NMR,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,EYE RES INST,BOSTON,MA 02114. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02115. RI Burns, Stephen/D-9259-2011 OI Burns, Stephen/0000-0001-5348-035X NR 17 TC 37 Z9 38 U1 2 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-6169 J9 CLIN VISION SCI PD NOV PY 1992 VL 7 IS 6 BP 521 EP & PG 0 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA KD812 UT WOS:A1992KD81200008 ER PT J AU ELSNER, AE AF ELSNER, AE TI SCANNING LASER OPHTHALMOSCOPY, TOMOGRAPHY, AND VISUAL FUNCTION EVALUATION SO CLINICAL VISION SCIENCES LA English DT Editorial Material ID EVOKED-RESPONSE; MACULAR SCOTOMA; RETINA C1 MASSACHUSETTS GEN HOSP, EYE RES INST, BOSTON, MA 02114 USA. RP HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, DEPT OPHTHALMOL, BOSTON, MA 02114 USA. NR 54 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6169 J9 CLIN VISION SCI PD NOV PY 1992 VL 7 IS 6 BP R5 EP R8 PG 4 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA KD812 UT WOS:A1992KD81200001 ER PT J AU SILVA, P EPSTEIN, FH SOLOMON, RJ AF SILVA, P EPSTEIN, FH SOLOMON, RJ TI THE EFFECT OF MERCURY ON CHLORIDE SECRETION IN THE SHARK (SQUALUS-ACANTHIAS) RECTAL GLAND SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY LA English DT Article ID THICK ASCENDING LIMB; SPINY DOGFISH; HENLES LOOP; TRANSPORT; SODIUM; MECHANISM; TUBULES AB 1. Mercuric chloride inhibited chloride secretion in a dose dependent way in isolated perfused rectal glands. The effect was readily apparent at a concentration of 10(-6) M and profound and irreversible at 10(-4) M. 2. The dithiol dithiothreitol (DTT) 10(-2) M completely prevented the effect of 10(-6) M mercuric chloride, reduced that at 10(-5) M and 10(-4) M, and made the inhibition at the latter concentration reversible. 3. Two organic mercurials, mersalyl and meralluride, that are effective diuretics in the mammalian kidney, and p-chloromercuribenzoyl sulfonic acid (PCMBS), that has no diuretic activity, had no effect on chloride secretion by the rectal gland. 4. The effect of mersalyl was not modified by lowering the pH of the solution perfusing the glands. 5. These results indicate that inorganic mercury and organic mercurials do not share the same mechanism of action. 6. The absence of an effect of organic mercurials on chloride transport in the rectal gland suggests that its effect on another chloride transporting epithelia, the thick ascending hmb of the loop of Henle, is not mediated by inhibition of the chloride cotransporter or Na+, K+-ATPase, common to both epithelia. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. JOSLIN DIABET CTR,DEPT MED,BOSTON,MA. HARVARD UNIV,CTR STUDY KIDNEY DIS,DEPT MED,CAMBRIDGE,MA 02138. MT DESERT ISL BIOL LAB,DEPT MED,SALSBURY COVE,ME 04672. RP SILVA, P (reprint author), NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215, USA. FU NICHD NIH HHS [NI-HDK18078]; NIEHS NIH HHS [ESO 3828] NR 28 TC 14 Z9 14 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0742-8413 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Pharmacol. Toxicol. Endocrinol. PD NOV PY 1992 VL 103 IS 3 BP 569 EP 575 DI 10.1016/0742-8413(92)90183-8 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA KG878 UT WOS:A1992KG87800024 PM 1363307 ER PT J AU FILIPEC, M PHAN, TM ZHAO, TZ RICE, BA MERCHANT, A FOSTER, CS AF FILIPEC, M PHAN, TM ZHAO, TZ RICE, BA MERCHANT, A FOSTER, CS TI TOPICAL CYCLOSPORINE-A AND CORNEAL WOUND-HEALING SO CORNEA LA English DT Article DE CYCLOSPORINE-A; CORNEAL WOUND HEALING; EPITHELIAL WOUND; STROMAL WOUND AB The effect of 2% topical cyclosporine A (CsA) ointment on corneal epithelial and stromal wound healing was evaluated in a masked, placebo-controlled study in rabbits. The difference in epithelial would healing rate in the treatment and placebo group was not statistically significant. There was also no difference in the values of bursting strength of 2-mm central penetrating wounds and in the measurement of hydroxyproline content in the central corneal buttons from the wounded area in both the groups. Clinical evaluation of the quality of regenerating epithelium, stromal edema, haze, and iritis did not reveal a difference between the two groups. There was a significantly higher incidence of conjunctival injection in the CsA-treated group. We conclude that topical cyclosporine A 2% does not significantly inhibit epithelial or stromal corneal wound healing. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,243 CHARLES ST,BOSTON,MA 02114. NR 0 TC 10 Z9 10 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 1992 VL 11 IS 6 BP 546 EP 552 DI 10.1097/00003226-199211000-00011 PG 7 WC Ophthalmology SC Ophthalmology GA JU431 UT WOS:A1992JU43100011 PM 1468217 ER PT J AU ZOLDHELYI, P FUSTER, V CHESEBRO, JH AF ZOLDHELYI, P FUSTER, V CHESEBRO, JH TI ANTITHROMBINS AS CONJUNCTIVE THERAPY IN ARTERIAL THROMBOLYSIS SO CORONARY ARTERY DISEASE LA English DT Review DE THROMBOSIS; THROMBOLYTIC THERAPY; THROMBIN; HEPARIN; HIRUDIN; ANTICOAGULATION; PLATELET INHIBITION; PLASMINOGEN ACTIVATORS ID SYNTHETIC THROMBIN INHIBITOR; PLASMINOGEN-ACTIVATOR; CORONARY THROMBOLYSIS; SELECTIVE-INHIBITION; RECOMBINANT HIRUDIN; DEPENDENT THROMBOSIS; ALPHA-THROMBIN; VESSEL WALL; FACTOR-XA; PLATELET C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,JACKSON 1401,32 FRUIT ST,BOSTON,MA 02114. MAYO CLIN & MAYO FDN,DIV CARDIOVASC DIS & INTERNAL MED,ROCHESTER,MN 55905. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 57 TC 19 Z9 19 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD NOV PY 1992 VL 3 IS 11 BP 1003 EP 1009 DI 10.1097/00019501-199211000-00003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JV664 UT WOS:A1992JV66400003 ER PT J AU JANG, IK FUSTER, V GOLD, HK AF JANG, IK FUSTER, V GOLD, HK TI ANTIPLATELETS SO CORONARY ARTERY DISEASE LA English DT Review DE PLATELET INHIBITORS; ARACHIDONIC ACIDS; ASPIRIN ID ACUTE MYOCARDIAL-INFARCTION; CANINE CORONARY-ARTERIES; TISSUE PLASMINOGEN-ACTIVATOR; THROMBOXANE-A2 SYNTHETASE INHIBITION; STREPTOKINASE-INDUCED THROMBOLYSIS; CYCLIC FLOW VARIATIONS; RECEPTOR ANTAGONISTS; BLOOD-FLOW; ONE MOLECULE; THROMBOSIS C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,JACKSON 14,32 FRUIT ST,BOSTON,MA 02114. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 39 TC 7 Z9 7 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD NOV PY 1992 VL 3 IS 11 BP 1030 EP 1036 DI 10.1097/00019501-199211000-00006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JV664 UT WOS:A1992JV66400006 ER PT J AU TOMPKINS, RG AF TOMPKINS, RG TI FULMINANT HEPATIC-FAILURE TREATED WITH ANTIENDOTOXIN ANTIBODY SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE ANTIBODIES, ANTIENDOTOXIN; ENDOTOXIN; LIVER FAILURE; SEPSIS; INFECTION; LIVER RP TOMPKINS, RG (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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 1992 VL 20 IS 11 BP 1507 EP 1507 DI 10.1097/00003246-199211000-00004 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA JY290 UT WOS:A1992JY29000004 PM 1424690 ER PT J AU RYAN, CM YARMUSH, ML BURKE, JF TOMPKINS, RG AF RYAN, CM YARMUSH, ML BURKE, JF TOMPKINS, RG TI INCREASED GUT PERMEABILITY EARLY AFTER BURNS CORRELATES WITH THE EXTENT OF BURN INJURY SO CRITICAL CARE MEDICINE LA English DT Article DE BURNS; PERMEABILITY; POLYETHYLENE GLYCOLS; SMALL INTESTINE; SEVERITY OF ILLNESS; TRAUMA; CRITICAL CARE; MACROMOLECULAR SYSTEMS; INJURY; CRITICAL ILLNESS; SEPSIS ID GRAM-NEGATIVE BACTEREMIA; INTESTINAL PERMEABILITY; MOLECULAR-WEIGHT; HEMORRHAGIC-SHOCK; THERMAL-INJURY; ABSORPTION; TRANSLOCATION; ENDOTOXEMIA; ANTIBODY; TRAUMA AB Objective: To determine if increased gut permeability within 48 hrs after burn injury correlates with the extent of injury, before sepsis and pulmonary disorders have complicated the clinical course. Design: Nonrandomized, controlled study. Patients: Consecutive patients admitted with burn injuries on >20% of body surface area. Interventions: Intestinal absorption and renal excretion of polyethylene glycol 3350 was used as the macromolecule to determine gut permeability; polyethylene glycol 400 intestinal absorption was used as an internal control for abnormal motility and malabsorption. Polyethylene glycol 3350 (40 g) and polyethylene glycol 400 (5 g) were administered enterally. Measurements and Main Results: Gut permeability was significantly increased early after the injury. The patients excreted 0.56 +/- 0.34% (n = 11) of polyethylene glycol 3350, compared with the amount (0.12 +/- 0.04%) (p < .05) previously reported in normal volunteers. There was no significant difference in the excretion of polyethylene glycol 400 in the patients (27.0 +/- 4.6%, n = 11) vs. the normal volunteers previously reported (26.3 +/- 5.1%, n = 12), suggesting normal intestinal motility and absorption. The percentage of excretion of polyethylene glycol 3350 correlated with the percentage body surface burned; patients with smaller injuries excreted 0.32 +/- 0.17% (n = 6), which was greater than normal and less than those values from patients with larger injuries, 0.84 +/- 0.25% (n = 5) (p < .001 by Tukey test). Conclusions: Using our newly developed method to separate and quantify polyethylene glycols in urine, gut permeability was found to be increased early after burn injury, which confirms a previous study using lactulose as the permeability probe. Furthermore, this increased gut permeability to polyethylene glycol 3350 correlated with the extent of the burn injury. C1 MASSACHUSETTS EYE & EAR INFIRM,SURG SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,SURG SERV,BOSTON,MA 02115. FU NIGMS NIH HHS [GM21700, GM07035] NR 32 TC 69 Z9 70 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 1992 VL 20 IS 11 BP 1508 EP 1512 DI 10.1097/00003246-199211000-00005 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA JY290 UT WOS:A1992JY29000005 PM 1424691 ER PT J AU MEYER, GS EAGLE, KA AF MEYER, GS EAGLE, KA TI PATIENT-CONTROLLED ANALGESIA MASKING PULMONARY EMBOLUS IN A POSTOPERATIVE-PATIENT SO CRITICAL CARE MEDICINE LA English DT Article DE PATIENT-CONTROLLED ANALGESIA; PULMONARY EMBOLUS; POSTOPERATIVE COMPLICATION; MORPHINE; CHEST PAIN; OSTEOTOMY; TEACHING; COUMADIN; DIAGNOSTIC DELAY; DEEP VENOUS THROMBOSIS; CARDIAC EMERGENCY; PULMONARY EMERGENCY; CRITICAL ILLNESS ID PAIN; MANAGEMENT RP MEYER, GS (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,GEN INTERNAL MED UNIT,BULFINCH 1,BOSTON,MA 02114, USA. NR 12 TC 8 Z9 8 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 1992 VL 20 IS 11 BP 1619 EP 1621 DI 10.1097/00003246-199211000-00022 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA JY290 UT WOS:A1992JY29000022 PM 1424708 ER PT J AU APLAN, PD NAKAHARA, K ORKIN, SH KIRSCH, IR AF APLAN, PD NAKAHARA, K ORKIN, SH KIRSCH, IR TI THE SCL GENE-PRODUCT - A POSITIVE REGULATOR OF ERYTHROID-DIFFERENTIATION SO EMBO JOURNAL LA English DT Article DE BHLH PROTEIN; ERYTHROID DIFFERENTIATION; SCL; TRANSCRIPTION FACTOR ID TRANSCRIPTION FACTOR GATA-1; T-CELL LEUKEMIA; DNA-BINDING PROTEINS; MAMMALIAN-CELLS; MYC PROTEINS; EXPRESSION; ERYTHROLEUKEMIA; LINE; ACTIVATION; MYOD AB The SCL (tal-1, TCL5) gene is a member of the basic domain, helix-loop-helix (bHLH) class of putative transcription factors. We found that (i) the SCL promoter for exon la contains a potential recognition site for GATA-binding transcription factors, (ii) SCL mRNA is expressed in all erythroid tissues and cell lines examined, and (iii) SCL mRNA increases upon induced differentiation of murine erythroleukemia (MEL) cells, and inferred that SCL may play a physiologic role in erythroid differentiation. We used gel shift and transfection assays to demonstrate that the GATA motif in the SCL promoter binds GATA-1 (and GATA-2), and also mediates transcriptional transactivation. To identify a role for SCL in erythroid differentiation, we generated stable transfectants of MEL and K562 (a human chronic myelogenous leukemia cell line that can differentiate along the erythroid pathway) cells overexpressing wild-type, antisense or mutant SCL cDNA. Increasing the level of SCL expression in two independent MEL lines (F4-6 and C19, a 745 derivative) and K562 cells increased the rate of spontaneous (i.e. in the absence of inducer) erythroid differentiation. Conversely, induced differentiation was inhibited in MEL transfectants expressing either antisense SCL cDNA or a mutant SCL lacking the basic domain. Our experiments suggest that the SCL gene can be a target for the erythroid transcription factor GATA-1 and that the SCL gene product serves as a positive regulator of erythroid differentiation. C1 NATL NAVAL MED CTR, NCI NAVY MED ONCOL BRANCH, BLDG 8, ROOM 5101, BETHESDA, MD 20889 USA. NCI, PEDIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. HARVARD UNIV, CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST, DEPT PEDIAT,DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. RI Aplan, Peter/K-9064-2016 NR 40 TC 226 Z9 228 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 NOV PY 1992 VL 11 IS 11 BP 4073 EP 4081 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JT328 UT WOS:A1992JT32800029 PM 1396592 ER PT J AU CROWLEY, WF JAMESON, JL AF CROWLEY, WF JAMESON, JL TI CLINICAL COUNTERPOINT - GONADOTROPIN-RELEASING-HORMONE DEFICIENCY - PERSPECTIVES FROM CLINICAL INVESTIGATION SO ENDOCRINE REVIEWS LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; SEX STEROID CONTROL; KALLMANN SYNDROME; CEREBELLAR-ATAXIA; GNRH GENE; MEN; SECRETION; REPRODUCTION; RESPONSES; FREQUENCY C1 MASSACHUSETTS GEN HOSP, DEPT MED, THYROID UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP MASSACHUSETTS GEN HOSP, DEPT MED, REPROD ENDOCRINE UNIT, BARTLETT HALL EXTENS 5, BOSTON, MA 02114 USA. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD-29164, R01 HD015788, U54 HD028138, U54 HD029164] NR 44 TC 39 Z9 39 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD NOV PY 1992 VL 13 IS 4 BP 635 EP 640 DI 10.1210/er.13.4.635 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KA703 UT WOS:A1992KA70300002 PM 1459047 ER PT J AU OHSAKI, Y TAKAHASHI, S SCARCEZ, T DEMULDER, A NISHIHARA, T WILLIAMS, R ROODMAN, GD AF OHSAKI, Y TAKAHASHI, S SCARCEZ, T DEMULDER, A NISHIHARA, T WILLIAMS, R ROODMAN, GD TI EVIDENCE FOR AN AUTOCRINE PARACRINE ROLE FOR INTERLEUKIN-6 IN BONE-RESORPTION BY GIANT-CELLS FROM GIANT-CELL TUMORS OF BONE SO ENDOCRINOLOGY LA English DT Article ID DNA-POLYMERASE; HORMONES AB Interleukin-6 (IL-6) is a multifunctional cytokine whose role in osteoclastic bone resorption has not been clearly defined. Therefore, we have used giant cells, which express many features of osteoclasts, from giant cell tumors of bone as a model to examine the role that IL-6 may play in human osteoclastic bone resorption. We found that conditioned medium from 24-h cultures of highly purified giant cells (10(6)/ml) contained large amounts of IL-6 (37.9 +/- 8.8 ng/ml), similar to the amount of IL-6 produced by tumor stromal cells (29.8 +/- 11.5 ng/ml). Giant cells and stromal cells from giant cell tumors expressed IL-6 mRNA, as indicated by polymerase chain reaction analysis and in situ hybridization studies, and immunohistochemical techniques demonstrated that the giant cells expressed IL-6 receptors. The addition of a neutralizing antibody to IL-6 significantly decreased the area of dentine resorbed by purified giant cells in a dose-dependent manner, and the addition of IL-6 to cultures of purified giant cells pretreated with anti-IL-6 restored the resorbing capacity of the giant cells. These data suggest that IL-6 may act as both an autocrine and a paracrine factor for human osteoclasts and play an important role in the bone-resorbing capacity of these cells. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NCI NIH HHS [CA-40035]; NIADDK NIH HHS [AM-35188]; NIAMS NIH HHS [AR-39539] NR 22 TC 138 Z9 142 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1992 VL 131 IS 5 BP 2229 EP 2234 DI 10.1210/en.131.5.2229 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JW338 UT WOS:A1992JW33800031 PM 1425421 ER PT J AU LIM, SK GARDELLA, TJ BABA, H NUSSBAUM, SR KRONENBERG, HM AF LIM, SK GARDELLA, TJ BABA, H NUSSBAUM, SR KRONENBERG, HM TI THE CARBOXY-TERMINUS OF PARATHYROID-HORMONE IS ESSENTIAL FOR HORMONE PROCESSING AND SECRETION SO ENDOCRINOLOGY LA English DT Article ID OSTEO-SARCOMA CELLS; PREPROPARATHYROID HORMONE; ENDOPLASMIC-RETICULUM; ESCHERICHIA-COLI; PROTEIN; SEQUENCE; BINDING; DEGRADATION; POLYMERASE; TRANSPORT AB The biological function of the carboxy-terminal portion of the PTH molecule is unknown. We hypothesized that the carboxy-terminus of PTH may be essential for hormone processing and secretion. To ascertain the potential role of the carboxy-terminus in transport through the secretory pathway, we constructed a series of carboxy-terminally deleted mutants of human preproPTH. PreproPTH and these truncated peptides were expressed in cell-free extracts and in acutely transfected COS 7 cells. Intact preproPTH(1-84) (115 residues) was processed to proPTH(1-84); the PTH was secreted very efficiently. In contrast, translocation across the membrane of the endoplasmic reticulum and signal sequence cleavage were mildly impaired for PTH(1-52) (83 residues), moderately impaired for PTH(1-40) (71 residues), and dramatically impaired for PTH(1-34) (65 residues). Subsequent cleavage of the prosequence and secretion from intact cells were also dramatically impaired for PTH(1-52) and undetectable for PTH(1-40) and PTH(1-34). We conclude that more than 65 residues are needed to cross the endoplasmic reticulum and that more than 83 residues are needed for efficient prosequence cleavage and secretion. Perhaps similar requirements for full transport through the secretory pathway explains why most secreted peptides are synthesized as long propeptides of at least 80 residues. C1 MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,WELLMAN 5,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 31 TC 18 Z9 18 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1992 VL 131 IS 5 BP 2325 EP 2330 DI 10.1210/en.131.5.2325 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JW338 UT WOS:A1992JW33800044 PM 1425431 ER PT J AU JELLINEK, MS TRILL, MD PASSIK, S FAWZY, FI BARD, M WEISMAN, A AF JELLINEK, MS TRILL, MD PASSIK, S FAWZY, FI BARD, M WEISMAN, A TI THE NEED FOR MULTIDISCIPLINARY TRAINING IN COUNSELING THE MEDICALLY ILL - REPORT OF THE TRAINING COMMITTEE OF THE LINDA-POLLIN-FOUNDATION SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article AB Training for medical counselors requires that medicine and psychiatry give up the position that counseling is only a negligible offshoot that almost any professional can readily do. Instead, counseling can be considered a generic concept that covers a wide variety of interventions designed to help patients cope with the complications and consequences of their chronic illness. This report outlines the principles and scope of training for consideration in the area of counseling the medically ill and reviews the current status of training programs in the fields of psychiatry, psychology, social work, and nursing. Recommendations are made for future directions, including role clarification for disciplines, building a credible research base, provision of guidelines and possible accreditation, and incorporating medical counseling into training fellowships. C1 AMER CANC SOC,ATLANTA,GA. MEM SLOAN KETTERING CANC CTR,PSYCHIAT SERV,NEW YORK,NY 10021. UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,LOS ANGELES,CA 90024. RP JELLINEK, MS (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,WANG BLDG,ROOM 725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV PY 1992 VL 14 IS 6 SU S BP S3 EP S10 PG 8 WC Psychiatry SC Psychiatry GA KE287 UT WOS:A1992KE28700002 PM 1340847 ER PT J AU JELLINEK, MS AF JELLINEK, MS TI A MODEL FOR COUNSELING THE MEDICALLY ILL - THE LINDA-POLLIN-FOUNDATION APPROACH - EPILOGUE SO GENERAL HOSPITAL PSYCHIATRY LA English DT Editorial Material RP JELLINEK, MS (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,WANG BLDG,ROOM 725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 5 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 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV PY 1992 VL 14 IS 6 SU S BP S50 EP S52 PG 3 WC Psychiatry SC Psychiatry GA KE287 UT WOS:A1992KE28700006 ER PT J AU OZELIUS, LJ KWIATKOWSKI, DJ SCHUBACK, DE BREAKEFIELD, XO WEXLER, NS GUSELLA, JF HAINES, JL AF OZELIUS, LJ KWIATKOWSKI, DJ SCHUBACK, DE BREAKEFIELD, XO WEXLER, NS GUSELLA, JF HAINES, JL TI A GENETIC-LINKAGE MAP OF HUMAN CHROMOSOME-9Q SO GENOMICS LA English DT Article ID DOPAMINE BETA-HYDROXYLASE; TAQI RFLP; LOCALIZATION; ABL; HETEROGENEITY; SEGREGATION; ASSIGNMENT; FAMILIES; LOCUS; AK1 C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROSCI,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV EXPTL MED,BOSTON,MA 02115. HEREDITARY DIS FDN,SANTA MONICA,CA 90404. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. RP OZELIUS, LJ (reprint author), MASSACHUSETTS GEN HOSP,NEUROGENET LAB,BOSTON,MA 02114, USA. RI Haines, Jonathan/C-3374-2012 FU NHGRI NIH HHS [HG000324, HG00169]; NINDS NIH HHS [NS28384] NR 48 TC 27 Z9 28 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 1992 VL 14 IS 3 BP 715 EP 720 DI 10.1016/S0888-7543(05)80173-9 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA JW352 UT WOS:A1992JW35200023 PM 1427899 ER PT J AU ZHOU, WG MCCOLLUM, MO LEVINE, BA OLSON, MS AF ZHOU, WG MCCOLLUM, MO LEVINE, BA OLSON, MS TI INFLAMMATION AND PLATELET-ACTIVATING-FACTOR PRODUCTION DURING HEPATIC ISCHEMIA REPERFUSION SO HEPATOLOGY LA English DT Article ID PERFUSED-RAT-LIVER; OXIDANT STRESS; KUPFFER CELLS; INJURY; GLYCOGENOLYSIS; STIMULATION; NEUTROPHIL; NECROSIS AB The role of platelet-activating factor as a potential mediator of hepatic inflammatory injury associated with liver ischemia/reperfusion was investigated using a partial no-flow model in rats in vivo. Platelet-activating factor levels of livers from sham-operated rats and from animals experiencing hepatic reperfusion for less than 6 hr were very low. They were observed to increase significantly after 12 hr of reperfusion and reached peak levels after a 24-hr reperfusion period, a time when maximal hepatic injury and inflammation occurred. Treatment of experimental rats with WEB2170, a platelet-activating factor receptor antagonist, attenuated the hepatic injury and inflammation, as evidenced by decreases in plasma ALT and in hepatocyte necrosis and neutrophil infiltration. Both inactivation of Kupffer cells with gadolinium chloride and inhibition of the formation of reactive oxygen species with allopurinol reduced platelet-activating factor production in the liver, whereas induction of neutropenia had no effect, suggesting that interaction of Kupffer cells with oxygen-derived free radicals may be a plausible mechanism for hepatic platelet-activating factor accumulation. It is concluded that platelet-activating factor contributes to the inflammatory consequences of ischemia/reperfusion underlying late-phase hepatic injury. C1 UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. FU NIADDK NIH HHS [AM-19473] NR 27 TC 90 Z9 91 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 NOV PY 1992 VL 16 IS 5 BP 1236 EP 1240 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JW848 UT WOS:A1992JW84800020 PM 1427662 ER PT J AU WONG, JT BONVENTRE, JV DUNN, S COLVIN, RB AF WONG, JT BONVENTRE, JV DUNN, S COLVIN, RB TI COMPARATIVE-STUDIES OF ISOLATED CD3-CD8, CD3-CD3, AND MONOVALENT CD3 BINDING ON CD8+ T-CELL ACTIVATION - MODEL OF PROGRESSIVE T-CELL RECEPTOR AGGREGATION SYNERGISM SO HUMAN IMMUNOLOGY LA English DT Article ID BISPECIFIC MONOCLONAL-ANTIBODIES; PERIPHERAL-BLOOD LYMPHOCYTES; DIFFERENT SURFACE-ANTIGENS; CLASS-I MOLECULES; CROSS-LINKING; COMPLEMENT-FIXATION; SELECTIVE BINDING; EXPRESSION; PROLIFERATION; CYTOLYSIS AB The TCR and CD8 complexes of CD8+ T cells bind to different regions of MHC class I molecules and both play important roles in the response of the CD8+ T cells to Ag/MHC on APCs. In this report, we mimicked common MHC binding with an anti-CD3: anti-CD8 (CD3,8) BSMAB to isolate the effect of CD3:CD8 pairing, compared this with the effect of CD3:CD3 pairing by the parental bivalent anti-CD3 MAB, and with monovalent anti-CD3 binding by an anti-CD3: anti-CD4 (CD3,4) BSMAB. CD3:CD8 pairing induced an increase in cytosolic free [Ca2+] 1.5 to 3.0-fold greater than the increase induced by CD3: CD3 pairing whereas monovalent CD3 binding induced only 20%-30% of the increase. Postbinding receptor migration studies suggested that microaggregation increased from monovalent CD3 binding to CD3:CD3 pairing to CD3:CD8 pairing. Further studies revealed that progressively higher concentrations of antibodies were needed from CD3,8 to CD3,3 to CD3,4 to initiate the same degree of DNA synthesis. These results demonstrated that Ti/CD3 and CD8 can indeed be bridged by a single molecule. A model of direct CD8:CD3 synergism was raised as a possible explanation for the enhanced activation induced by CD3:CD8 pairing. The observed parallel between all three parameters and the number of TCRs that can be directly linked by the Abs raised a nonmutually exclusive model whereby CD3 binding induces activated TCR intermediaries (aTCRi) that progressively synergize with other adjacent aTCRis. In this model, this dominant inter-aTCRi synergism may be enhanced by the di- and multimeric CD8alpha chains serving as aTCRi-aggregation foci. C1 MASSACHUSETTS GEN HOSP,DEPT MED,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ALLERGY IMMUNOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP WONG, JT (reprint author), MASSACHUSETTS GEN HOSP,IMMUNOPARASITOL UNIT,COX 5,BOSTON,MA 02114, USA. FU NCI NIH HHS [T32-CA09216]; NIAID NIH HHS [AI27050]; NIDDK NIH HHS [DK 38452] NR 31 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD NOV PY 1992 VL 35 IS 3 BP 200 EP 208 DI 10.1016/0198-8859(92)90106-W PG 9 WC Immunology SC Immunology GA KF450 UT WOS:A1992KF45000009 PM 1293084 ER PT J AU JOOS, S FALK, MH LICHTER, P HALUSKA, FG HENGLEIN, B LENOIR, GM BORNKAMM, GW AF JOOS, S FALK, MH LICHTER, P HALUSKA, FG HENGLEIN, B LENOIR, GM BORNKAMM, GW TI VARIABLE BREAKPOINTS IN BURKITT-LYMPHOMA CELLS WITH CHROMOSOMAL T(8-14) TRANSLOCATION SEPARATE C-MYC AND THE IGH LOCUS UP TO SEVERAL 100 KB SO HUMAN MOLECULAR GENETICS LA English DT Article ID HEAVY-CHAIN LOCUS; CONSTANT REGION; CELLULAR ONCOGENES; LOCATED DOWNSTREAM; NAMALVA CELLS; PHYSICAL MAP; MU-GENE; IMMUNOGLOBULIN; ENHANCER; TRANSCRIPTION AB In about 80% of Burkitt's lymphoma cases, the tumour cell harbours a reciprocal chromosomal translocation which invariably transposes the coding exons 2 and 3 of c-myc from chromosome 8 to the immunoglobulin heavy chain locus on chromosome 14. Those t(8;14) translocations which disrupt chromosome 8 within or close to the c-myc gene are well documented. In this study we have focussed on t(8;14) translocations with the chromosomal breakpoint far upstream of c-myc. We analyzed the breakpoint position in 44 BL cell lines with t(8;14) translocations of different geographical origin and identified 9 cell lines with the breakpoint more than 14 kb upstream of c-myc. In these cell lines the positions of the translocation junctions on the derivative chromosomes 8q- and 14q+ were mapped by pulsed field gel electrophoresis and multicolour fluorescence in situ hybridization. The breakpoints occur at distances between 55 and more than 340 kb upstream of c-myc with no preferential site on chromosome 8. On chromosome 14, however, the translocation breakpoints are clustered in a narrow region 5' of the intron enhancer of the immunoglobulin heavy chain gene. In 7 of 9 cases, the enhancer is fused to the c-myc bearing sequences of chromosome 8. In two cases, the translocation has occurred in switch A and downstream of Cmu, respectively. The impact of these results with respect to the hypothesis, that cis-regulatory sequences from the immunoglobulin heavy chain locus can deregulate c-myc expression in a manner sufficient for tumour formation, is discussed. C1 GSF FORSCH ZENTRUM UMWELT & GESUNDHEIT GMBH, INST KLIN MOLEKULARBIOL & TUMORGENET, W-8000 MUNICH 70, Germany. DEUTSCH KREBSFORSCHUNGSZENTRUM, ANGEW TUMORVIROL, W-6900 HEIDELBERG, Germany. FAC MED, INSERM, U 75, NECKER ENFANTS MALAD, F-75730 PARIS 15, France. CTR INT RECH CANC, F-69003 LYON, France. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. NR 49 TC 69 Z9 69 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1992 VL 1 IS 8 BP 625 EP 632 DI 10.1093/hmg/1.8.625 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JY377 UT WOS:A1992JY37700011 PM 1301171 ER PT J AU DONALDSON, DH ROSEN, DR OREGAN, J SAPP, PC HORVITZ, HR GUSELLA, JF HAINES, JL PESTKA, S JUNG V NUSBAUM, C PATTERSON, D BROWN, RH AF DONALDSON, DH ROSEN, DR OREGAN, J SAPP, PC HORVITZ, HR GUSELLA, JF HAINES, JL PESTKA, S JUNG, V NUSBAUM, C PATTERSON, D BROWN, RH TI 2 INDEPENDENT DINUCLEOTIDE REPEAT POLYMORPHISMS AT THE D21S235 LOCUS (21Q22.1) SO HUMAN MOLECULAR GENETICS LA English DT Note C1 UNIV COLORADO, HLTH SCI CTR, DEPT NEUROL, DENVER, CO 80262 USA. UNIV COLORADO, HLTH SCI CTR, ELEANOR ROOSEVELT INST CANC RES, DENVER, CO 80262 USA. MASSACHUSETTS GEN HOSP, DAY NEUROMUSCULAR RES LAB, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET LAB, BOSTON, MA 02114 USA. MIT, HOWARD HUGHES MED INST, CAMBRIDGE, MA 02139 USA. ROBERT WOOD JOHNSON MED SCH, DEPT MOLEC GENET & DENT NEW JERSEY, PISCATAWAY, NJ USA. RI Haines, Jonathan/C-3374-2012 FU NHGRI NIH HHS [HG00317, HG00324]; NIA NIH HHS [AG00029] NR 1 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1992 VL 1 IS 8 BP 651 EP 651 DI 10.1093/hmg/1.8.651 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA JY377 UT WOS:A1992JY37700018 PM 1301176 ER PT J AU WOLF, BC SHEAHAN, K DECOSTE, D VARIAKOJIS, D ALPERN, HD HASELOW, RE AF WOLF, BC SHEAHAN, K DECOSTE, D VARIAKOJIS, D ALPERN, HD HASELOW, RE TI IMMUNOHISTOCHEMICAL ANALYSIS OF SMALL-CELL TUMORS OF THE THYROID-GLAND - AN EASTERN COOPERATIVE ONCOLOGY GROUP-STUDY SO HUMAN PATHOLOGY LA English DT Article DE THYROID; LYMPHOMA; PARAFFIN-REACTIVE ANTIBODIES; IMMUNOHISTOCHEMISTRY ID NON-HODGKINS LYMPHOMAS; MONOCLONAL-ANTIBODIES; MALIGNANT-LYMPHOMA; PARAFFIN SECTIONS; TISSUE-SECTIONS; IMMUNOPEROXIDASE; MALT; MB2 C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. BOSTON UNIV,SCH MED,MALLORY INST PATHOL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. NORTHWESTERN UNIV,MED CTR,DEPT PATHOL,CHICAGO,IL 60611. MARY IMOGENE BASSETT HOSP,DEPT PATHOL,COOPERSTOWN,NY 13326. METRO MINNEAPOLIS CCOP,DEPT RADIAT THERAPY,MINNEAPOLIS,MN. RP WOLF, BC (reprint author), UNION UNIV,DEPT PATHOL & LAB MED,A-81,ALBANY,NY 12208, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA 06594, CA 17145, CA 23318] NR 39 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 1992 VL 23 IS 11 BP 1252 EP 1261 DI 10.1016/0046-8177(92)90293-C PG 10 WC Pathology SC Pathology GA JX935 UT WOS:A1992JX93500010 PM 1330875 ER PT J AU VIVIER, E ROCHET, N ACKERLY, M PETRINI, J LEVINE, H DALEY, J ANDERSON, P AF VIVIER, E ROCHET, N ACKERLY, M PETRINI, J LEVINE, H DALEY, J ANDERSON, P TI SIGNALING FUNCTION OF RECONSTITUTED CD16-ZETA-GAMMA RECEPTOR COMPLEX ISOFORMS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE FC RECEPTORS NK CELLS; SIGNAL TRANSDUCTION; T CELL ANTIGEN RECEPTOR ID T-CELL-RECEPTOR; NATURAL-KILLER-CELLS; FC-EPSILON-RI; AFFINITY IGE RECEPTOR; TYROSINE PHOSPHORYLATION; ANTIGEN RECEPTOR; ZETA-CHAIN; GAMMA-SUBUNIT; EXPRESSION; ACTIVATION AB Natural killer cells express an Fc receptor for IgG (CD16) in association with disulfide-linked dimers composed of two homologous subunits: the zeta chain of the T cell antigen receptor complex and the gamma chain of the mast cell/basophil Fc receptor for IgE. The ability of zeta and gamma to transduce CD16-mediated activation signals was compared by reconstituting distinct CD16 receptor isoforms composed of various combinations of zeta- and gamma-containing dimers. Stably transformed non-hematopoietic and hematopoietic cell lines were established that expressed chimeric molecules comprising the extracellular domain of CD16 joined to the transmembrane and intracellular domains of zeta or gamma. Reconstituted CD16 receptor complexes triggered Ca2+ influx, tyrosine phosphorylation, and IL-2 production in stable transformants of the Jurkat T cell line. However, cross-linking of the CD16/gamma chimera induced a specific pattern of tyrosine phosphorylation and was more efficient at signal transduction than a CD16,zeta-zeta complex, suggesting that zeta and gamma cytoplasmic domains may be coupled to distinct tyrosine kinase pathways that differentially regulate CD16-mediated activation signals. By contrast, both CD16/zeta and CD16/gamma chimeric molecules were not functional in stable transformants of the fibroblast Chinese Hamster Ovary cell line, indicating a requirement for downstream signaling components present in hematopoietic cells. Finally, the zeta transmembrane domain appears to preferentially associate with CD16 rather than the CD3:TCR complex, suggesting that a hierarchy of molecular interactions governs NK and T cell differentiation. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RHEUMATOL & IMMUNOL,BOSTON,MA 02115. RP VIVIER, E (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 50 TC 38 Z9 40 U1 1 U2 2 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 NOV PY 1992 VL 4 IS 11 BP 1313 EP 1323 DI 10.1093/intimm/4.11.1313 PG 11 WC Immunology SC Immunology GA JZ112 UT WOS:A1992JZ11200013 PM 1472481 ER PT J AU TEICHER, BA HERMAN, TS MENON, K KORBUT, TT AF TEICHER, BA HERMAN, TS MENON, K KORBUT, TT TI WHOLE-BODY HYPERTHERMIA AS AN ADJUVANT TO TREATMENT WITH PLATINUM COMPLEXES WITH OR WITHOUT ETANIDAZOLE IN MICE BEARING THE LEWIS LUNG-CARCINOMA OR THE FSALL FIBROSARCOMA SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE WHOLE-BODY HYPERTHERMIA; PLATINUM COMPLEXES; ETANIDAZOLE; LUNG METASTASES ID MELPHALAN ANTITUMOR-ACTIVITY; PHASE-I TRIAL; FLUOSOL-DA; NORMAL TISSUE; CIS-DIAMMINEDICHLOROPLATINUM; ALKYLATING-AGENTS; ADVANCED CANCER; RENAL INJURY; TUMOR; CIS-DIAMMINEDICHLOROPLATINUM(II) AB The response of s.c. primary and metastatic Lewis lung carcinoma to five antitumour platinum complexes with or without tolerable whole-body hyperthermia (60 min to reach temperature then 60 min at 42-degrees-C) was examined. The whole-body hyperthermia treatment produced about 2.8 days of tumour growth delay in the s. c. tumours. The addition of whole-body hyperthermia to treatment with each of the platinum complexes was well tolerated by the animals and increases of 1.6-2.0-fold in tumour growth delay resulted with the combined treatment compared with the platinum complexes alone. The combination of etanidazole (1 g/kg) and the platinum complexes followed by whole-body hyperthermia produced marked increases in tumour growth delay ranging from 2.5- to 3.6-fold over the growth delays obtained with the platinum complexes alone. FSaLLC tumour cell survival and bone marrow CFU-GM experiments indicated that local hyperthermia (43-degrees-C, 30 min) produced greater potentiation of the cytotoxicity of three platinum complexes than did whole-body hyperthermia (42-degrees-C, 60 min). Only the complete treatments including whole-body hyperthermia/etanidazole and the platinum complexes were effective in significantly reducing the numbers of lung metastases formed from s.c. primary tumours. Serum urea nitrogen and creatinine levels were monitored over a time-course post-treatment. Although some treatment combinations caused elevations in these normal tissue parameters by day 12 post-treatment both serum urea nitrogen and serum creatinine returned to the levels of the untreated control animals. C1 JOINT CTR RADIAT THERAPY, BOSTON, MA 02115 USA. RP TEICHER, BA (reprint author), HARVARD UNIV, SCH MED, DANA FARBER CANC INST, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [R01-CA50174] NR 62 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD NOV-DEC PY 1992 VL 8 IS 6 BP 783 EP 794 DI 10.3109/02656739209005026 PG 12 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA KC569 UT WOS:A1992KC56900007 PM 1479204 ER PT J AU HAFFNER, SM BAUER, RL AF HAFFNER, SM BAUER, RL TI EXCESS ANDROGENICITY ONLY PARTIALLY EXPLAINS THE RELATIONSHIP BETWEEN OBESITY AND BONE-DENSITY IN PREMENOPAUSAL WOMEN SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE SEX HORMONES; BONE DENSITY; OSTEOPOROSIS ID HORMONE-BINDING GLOBULIN; BODY-FAT DISTRIBUTION; MEXICAN-AMERICANS; ADRENAL ANDROGENS; MENOPAUSAL WOMEN; SEX STEROIDS; RISK-FACTORS; OSTEOPOROSIS; FRACTURES; ADIPOSITY AB Obese subjects have increased bone density relative to non-obese subjects yet this relationship is not fully understood. We examined whether alterations in sex hormones or binding proteins might explain the effect of obesity on osteoporosis in 83 premenopausal women from the San Antonio Heart Study, a population-based study of diabetes. We measured total testosterone, oestradiol, oestrone, sex hormone binding globulin (SHBG), and serum dehydroepiandrosterone sulphate (DHEA-SO4). Bone density was assessed by a Hologic dual photon absorptometer. Lumbar spine and femoral neck density were positively correlated with body mass index (BMI). In addition, femoral neck density was positively correlated with DHEA-SO4. BMI was negatively correlated with SHBG. After adjustment for sex hormones by multiple linear regression a positive association between bone density and obesity still exists suggesting that the association between obesity and bone density is at least partially independent of sex steroids in premenopausal women. C1 AUDIE L MURPHY MEM VET ADM MED CTR,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV CLIN EPIDEMIOL,SAN ANTONIO,TX 78284. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NHLBI NIH HHS [R01 HL24799, R37 HL36820]; NIAMS NIH HHS [R01 AR39794] NR 29 TC 26 Z9 26 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 1992 VL 16 IS 11 BP 869 EP 874 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA JW697 UT WOS:A1992JW69700004 PM 1337341 ER PT J AU TEICHER, BA HOLDEN, SA ARA, G SOTOMAYOR, EA MENON, K TARBELL, NJ SALLAN, SE AF TEICHER, BA HOLDEN, SA ARA, G SOTOMAYOR, EA MENON, K TARBELL, NJ SALLAN, SE TI ETANIDAZOLE AS A MODULATOR OF COMBINED MODALITY THERAPY IN THE RAT 9L-GLIOSARCOMA SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ETANIDAZOLE; GLIOSARCOMA ID BRAIN-TUMORS; PRERADIATION CHEMOTHERAPY; FSAIIC FIBROSARCOMA; ALKYLATING-AGENTS; FLUOSOL-DA; MEDULLOBLASTOMA; CHILDREN; RADIATION; CYCLOPHOSPHAMIDE; MISONIDAZOLE AB The use of chemotherapy has led to improved treatment outcome for some pediatric patients with medulloblastoma. We have used a pre-radiation chemotherapy regimen consisting of vincristine and CDDP. The 9L gliosarcoma implanted intracranially and subcutaneously in the same animals was used as a preclinical model system to assess the efficacy of treatment combinations including: vincristine, CDDP, cyclo-phosphamide, etanidazole and radiation. The experimental endpoints were percent increase-in-lifespan, tumor growth delay and tumor cell survival. Both the tumor growth delay and percent increase-in-lifespan improved as the number of agents included in the chemotherapy regimen increased. so that the chemotherapy regimen including all four agents (ETA/VIN/CDDP/CTX) resulted in the greatest tumor growth delay (23.6 +/- 1.5 days) and the greatest increase-in-lifespan (35.8%). When radiation (20 Gray, single dose) was added to the treatment regimens the combinations of ETA/CTX/X-ray and ETA/VIN/CDDP/CTX/X-ray resulted in equivalent tumor growth delays (25.2 +/- 1.3 days and 25.8 +/- 1.7 days, respectively), while the greatest increase-in-lifespan (39.1%) was obtained with the five agent combination. The response of the 9L gliosarcoma to CDDP and cyclophosphamide over a dosage range was very similar to that of the murine FSaII fibrosarcoma. Our results indicate that etanidazole may be an effective chemosensitizer of combination chemotherapy and combined modality treatment regimens for brain tumors. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP TEICHER, BA (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 37 TC 10 Z9 10 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 NOV PY 1992 VL 1 IS 6 BP 625 EP 630 PG 6 WC Oncology SC Oncology GA JV123 UT WOS:A1992JV12300003 PM 21584591 ER PT J AU SPRIGGS, DR TONDINI, C AF SPRIGGS, DR TONDINI, C TI TAXOL ADMINISTERED AS A 120 HOUR INFUSION SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE TAXOL; PHASE-I; PROLONGED INFUSION ID AGENT; CELLS AB A Phase I trial of Taxol administered as a 120 h infusion once every 3 weeks was conducted in 20 patients with advanced cancer. The initial dose was 5 mg/m2/d (25 mg/m2 total dose) and patients received 10 mg/m2/d, 25 mg/m2/d, 30 mg/m2/d and 36 mg/m2/d. Forty-four courses of taxol were administered and all patients were evaluable for toxicity. Grade 4 leukopenia was the dose limiting toxicity observed in 50% of patients treated with 36 mg/m2/d. Significant mucositis was also observed at 30 and 36 mg/m2/d. All toxicity resolved within three weeks of treatment and no cumulative toxicity was observed. No neurotoxicity or cardiotoxicity was observed and no episodes of hypersensitivity reaction were noted. We conclude that 30 mg/m2/d is an appropriate dose for phase II testing of this schedule. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. INST NAZL TUMORI,DIV MED ONCOL,I-20133 MILAN,ITALY. RP SPRIGGS, DR (reprint author), UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT HUMAN ONCOL,K4-414,600 HIGHLAND AVE,MADISON,WI 53792, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 10 TC 55 Z9 55 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 1992 VL 10 IS 4 BP 275 EP 278 DI 10.1007/BF00944181 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA KF634 UT WOS:A1992KF63400005 PM 1362568 ER PT J AU BAILEY, H KOHLER, P TUTTLE, R CARBONE, PP HOHNEKER, JA CLENDENINN, NJ WILDING, G AF BAILEY, H KOHLER, P TUTTLE, R CARBONE, PP HOHNEKER, JA CLENDENINN, NJ WILDING, G TI PHASE-I EVALUATION OF 773U82-HCL IN A 2-HOUR INFUSION REPEATED DAILY FOR 3 DAYS SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE 773U82-HCL; ARYLMETHYLAMINOPROPANEDIOLS; PHASE-I ID CLINICAL-PHARMACOLOGY TRIAL; SINGLE-DOSE SCHEDULE; MESYLATE AB One of a novel series of compounds (AMAPS or arylmethylaminopropanediols), 773U82-HCl has shown significant antitumor activity in in vitro and in in vivo tumor systems, but has less animal CNS toxicity than the lead compound in the same series (crisnatol). This study was designed to evaluate the pharmacokinetics, qualitative and quantitative toxicities of 773U82-HCl and to determine the recommended phase II dose (MTD) of 773U82-HCl given as a short infusion daily for 3 days every 3 weeks. Twenty-nine patients with refractory malignancies received 79 courses over 9 dose levels during this study. Doses ranged from 50 to 1060 mg/m2/d x 3 days. Due to the possibility of local hemolysis with concentrations > 1.5 mg/ml, drug was administered in solutions containing less-than-or-equal-to 1.5 mg/ml. Because large volumes were needed at the higher dose levels, the infusion duration was increased from 2 hours to 4 hours. Mild to moderate nausea, vomiting, fatigue, dizziness and headaches were observed. Myelosuppression was the dose limiting toxicity. The recommended phase II dose and schedule was determined to be 800 mg/m2/d x 3d every 3 weeks. 773U82-HCl plasma concentration-time data were analyzed using a two-compartment pharmacokinetic model. The t1/2beta averaged 6 hours and the total body clearance was 75.9 L/hr/m2. The volume of distribution (Vdss) was large, averaging 470 L/m2. C1 UNIV WISCONSIN,CTR CLIN CANC,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. MERITER MADISON GEN HOSP,MADISON,WI 53715. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [5 T32 CA09614]; NCRR NIH HHS [RR031186] NR 9 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 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 1992 VL 10 IS 4 BP 279 EP 287 DI 10.1007/BF00944182 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA KF634 UT WOS:A1992KF63400006 PM 1487401 ER PT J AU FALKSON, G HUNT, M BORDEN, EC HAYES, JA FALKSON, CI SMITH, TJ AF FALKSON, G HUNT, M BORDEN, EC HAYES, JA FALKSON, CI SMITH, TJ TI AN EXTENDED PHASE-II TRIAL OF IFOSFAMIDE PLUS MESNA IN MALIGNANT MESOTHELIOMA SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE MALIGNANT MESOTHELIOMA; IFOSFAMIDE PLUS MESNA ID COOPERATIVE-ONCOLOGY-GROUP; PLEURAL MESOTHELIOMA; EXPERIENCE; TOXICITY AB Forty three patients with histologically confirmed malignant mesothelioma were entered onto an Eastern Cooperative Oncology Group phase II study of ifosfamide given with mesna. Eligibility criteria included adequate performance status, hemogram and renal functions. Ifosfamide was given at 1.5 g/m2 in 200 ml of normal saline over 30 minutes by intravenous infusion on days 1 to 5 of each 21 day cycle. Mesna was given at 300 mg/m2 on each day of ifosfamide at 0,4 and 8 hours. Two patients were cancelled and one patient was ineligible. The most common toxicity was haematologic. More than 50% of the patients had at least one episode of severe or life threatening toxicity and 2 patients had lethal toxicity (1 renal and 1 pulmonary oedema attributed to treatment), and an additional 4 patients died while on study (2 of cardiac and 2 of cerebral vascular disease not considered directly related to treatment). Of the 40 eligible patients one was unevaluable for response, and one patient had a partial response lasting 6.3 months. Twenty four patients had a no change status with a median duration of 5 months. The median time to treatment failure for all eligible patients was 2.5 months. The median overall survival time (from registration) for all eligible patients was 6.9 months. In multi variable models, factors that predicted for a statistically significant poorer survival were age greater-than-or-equal-to 62, stage greater-than-or-equal-to 3, performance status poorer than 0 to 1 and prior surgery (i.e.: more than biopsy). The severe toxicity, documented in more than half of the patients, precludes any further dose escalation of ifosfamide in these patients. With only one. response among 39 evaluable patients, it is concluded, from this extended phase II trial, that ifosfamide does not have a worthwhile therapeutic effect in patients with malignant mesothelioma. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53706. BOSTON VA HOSP,BOSTON,MA. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. RP FALKSON, G (reprint author), UNIV PRETORIA,DEPT MED ONCOL,POB 667,PRETORIA 0001,SOUTH AFRICA. FU NCI NIH HHS [CA 21692, CA 21115, CA 21076] NR 28 TC 28 Z9 28 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD NOV PY 1992 VL 10 IS 4 BP 337 EP 343 DI 10.1007/BF00944192 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA KF634 UT WOS:A1992KF63400016 PM 1487409 ER PT J AU DEZUBE, BJ PARDEE, AB BECKETT, LA AHLERS, CM ECTO, L ALLENRYAN, J ANISOWICZ, A SAGER, R CRUMPACKER, CS AF DEZUBE, BJ PARDEE, AB BECKETT, LA AHLERS, CM ECTO, L ALLENRYAN, J ANISOWICZ, A SAGER, R CRUMPACKER, CS TI CYTOKINE DYSREGULATION IN AIDS - INVIVO OVEREXPRESSION OF MESSENGER-RNA OF TUMOR-NECROSIS-FACTOR-ALPHA AND ITS CORRELATION WITH THAT OF THE INFLAMMATORY CYTOKINE GRO SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE CYTOKINES; TUMOR NECROSIS FACTOR; CACHECTIN; GRO; PENTOXIFYLLINE; MELANOMA GROWTH STIMULATORY ACTIVITY (MGSA) ID IMMUNODEFICIENCY-VIRUS TYPE-1; PERIPHERAL-BLOOD MONOCYTES; MONONUCLEAR-CELLS; T-CELLS; EXPRESSION; CACHECTIN; REPLICATION; INDUCTION; PENTOXIFYLLINE; BINDING AB The human immunodeficiency virus establishes an intimate interaction with the immune system. The virus can use cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-I (Il-1), to regulate its own expression by modifying the normal immunoregulatory network. We demonstrate that mRNA of the cytokine TNF-alpha from peripheral blood mononuclear cells is overexpressed in virtually all patients with AIDS who do not have active opportunistic infections compared with uninfected volunteers (p < 0.0001). This overexpression correlates with elevated mRNA levels of the recently discovered GRO (p < 0.05), a cytokine involved in the inflammatory response. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,DIV INFECT DIS,BOSTON,MA 02215. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP DEZUBE, BJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,D810A,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [N0-AI-62534, N0-AI-95030] NR 38 TC 61 Z9 63 U1 1 U2 2 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 NOV PY 1992 VL 5 IS 11 BP 1099 EP 1104 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA JV265 UT WOS:A1992JV26500006 PM 1403638 ER PT J AU GARPESTAD, E KATAYAMA, H PARKER, JA RINGLER, J LILLY, J YASUDA, T MOORE, RH STRAUSS, HW WEISS, JW AF GARPESTAD, E KATAYAMA, H PARKER, JA RINGLER, J LILLY, J YASUDA, T MOORE, RH STRAUSS, HW WEISS, JW TI STROKE VOLUME AND CARDIAC-OUTPUT DECREASE AT TERMINATION OF OBSTRUCTIVE APNEAS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE OBSTRUCTIVE SLEEP APNEA; HEMODYNAMICS ID VENTRICULAR-FUNCTION MONITOR; SLEEP-INDUCED APNEA; HEMODYNAMICS; PRESSURE; ASSOCIATION; INFARCTION; PULMONARY; DISEASE AB Patients with obstructive sleep apnea (OSA) experience repetitive nocturnal oscillations of systemic arterial pressure that occur in association with changes in respiration and changes in sleep state. To investigate cardiac function during the cycle of obstruction (apnea) and resumption of ventilation (recovery), we continuously measured left ventricular stroke volume (LVSV) and mean arterial blood pressure (MAP) during non-rapid-eye-movement sleep in six males with severe OSA (apnea/hypopnea index greater-than-or-equal-to 30 events/h associated with oxygen saturation <82%). LVSV was assessed continuously using an ambulatory ventricular function monitor (VEST; Capintec). The apnea-recovery cycle was divided into three phases: 1) early apnea (EA), 2) late apnea (LA), and 3) recovery (Rec). In all subjects recovery was associated with an abrupt decrease in LVSV [54.0 +/- 14.5 (SD) ml] compared with either EA (91.4 +/- 14.7 ml; P < 0.001) or LA (77.1 +/- 15.2 ml; P < 0.005). Although heart rate increased with recovery, the increase was not sufficient to compensate for the decrease in LVSV so that cardiac output (CO) fell (EA: 6,247 +/- 739 ml/min; LA: 5,741 +/- 1,094 ml/min; Rec: 4,601 +/- 1,249 ml/min; EA vs. Rec, P < 0.01; LA vs. Rec, P < 0.025). Recovery was also associated with a significant increase in MAP. We speculate that such abrupt decreases in LVSV and CO at apnea termination, occurring coincident with the nadir of oxygen saturation, may further compromise tissue oxygen delivery. C1 BETH ISRAEL HOSP,DIV PULM,330 BROOKLINE AVE,BOSTON,MA 02215. BETH ISRAEL HOSP,CHARLES A DANA INST,BOSTON,MA 02215. BETH ISRAEL HOSP,THORNDIKE LAB,BOSTON,MA 02215. BETH ISRAEL HOSP,CTR SLEEP DISORDERS,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT RADIOL,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-07633, HL-46951] NR 29 TC 100 Z9 103 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 NOV PY 1992 VL 73 IS 5 BP 1743 EP 1748 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA JZ596 UT WOS:A1992JZ59600008 PM 1474046 ER PT J AU BADR, MS SKATRUD, JB DEMPSEY, JA AF BADR, MS SKATRUD, JB DEMPSEY, JA TI DETERMINANTS OF POSTSTIMULUS POTENTIATION IN HUMANS DURING NREM SLEEP SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE AFTERDISCHARGE MECHANISM; HYPOXIA; CENTRAL APNEA; PERIODIC BREATHING; HYPOVENTILATION ID BRAIN BLOOD-FLOW; VENTILATORY RESPONSES; CHRONIC HYPOXIA; RESPIRATORY DRIVE; SUSTAINED HYPOXIA; AFTERDISCHARGE; CATS; HYPERVENTILATION; ACCLIMATIZATION; HYPERCAPNIA AB To test whether active hyperventilation activates the "afterdischarge" mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PET(O2)) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PET(O2) 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PET(CO2)) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PET(O2) 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PET(O2) 64 +/- 4 Torr, PET(CO2) decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of afterdischarge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing. C1 UNIV WISCONSIN,DEPT PREVENT MED,MADISON,WI 53702. UNIV WISCONSIN,WILLIAM S MIDDLETON MEM VET HOSP,MED SERV,MADISON,WI 53702. UNIV WISCONSIN,DEPT MED,JOHN RANKIN LAB PREVENT MED,MADISON,WI 53702. FU NHLBI NIH HHS [HL-42242, HL-02588] NR 44 TC 69 Z9 69 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 NOV PY 1992 VL 73 IS 5 BP 1958 EP 1971 PG 14 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA JZ596 UT WOS:A1992JZ59600039 PM 1474073 ER PT J AU DEMULDER, A SUGGS, SV ZSEBO, KM SCARCEZ, T ROODMAN, GD AF DEMULDER, A SUGGS, SV ZSEBO, KM SCARCEZ, T ROODMAN, GD TI EFFECTS OF STEM-CELL FACTOR ON OSTEOCLAST-LIKE CELL-FORMATION IN LONG-TERM HUMAN MARROW CULTURES SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID HUMAN-BONE MARROW; HEMATOPOIETIC PROGENITOR CELLS; GROWTH-FACTOR; C-KIT; MULTINUCLEATED CELLS; SI-LOCUS; COLONY FORMATION; LIGAND; MOUSE; PRECURSORS AB Stem cell factor (SCF) is a newly described hematopoietic growth factor that stimulates the growth of primitive hematopoietic progenitors and mast cells. Since the osteoclast precursor is hematopoietic in origin, we tested SCF for its capacity to stimulate the formation of osteoclast-like multinucleated cells (MNC) in long-term human marrow cultures. These MNC express an osteoclast phenotype and form resorption lacunae on calcified matrices. Addition of SCF alone (0.1 pg/ml to 100 ng/ml) to long-term marrow cultures did not increase MNC formation. However, treatment of these cultures sequentially with SCF for 1 week followed by 1,25-(OH)2D3 for the second and third weeks of culture significantly enhanced MNC formation. [H-3]Thymidine incorporation studies showed that SCF increased the proliferation of MNC precursors. These data suggested that SCF was acting on early MNC precursors. We then tested the capacity of SCF to stimulate the formation of colonies of committed precursors for osteoclast-like MNC. SCF (20 pg/ml to 20 ng/ml) enhanced osteoclast precursor formation in unfractionated bone marrow mononuclear cells but was unable to increase osteoclast precursor formation when a highly purified population of hematopoietic precursors was used as the target cells for SCF. These data suggest that SCF works in concert with other factors produced by nonhematopoietic marrow cells to increase the precursor pool for osteoclasts and that other factors, such as 1,25-(OH)2D3, complete the differentiation process to the mature osteoclast. C1 AUDIE L MURPHY MEM VET ADM MED CTR,RES SERV,7400 MERTON MINTER BLVD,SAN ANTONIO,TX. AMGEN CORP,THOUSAND OAKS,CA. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. FU NCI NIH HHS [CA-40035]; NIADDK NIH HHS [AM35188]; NIAMS NIH HHS [AR 39539] NR 29 TC 33 Z9 33 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 1992 VL 7 IS 11 BP 1337 EP 1344 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JY182 UT WOS:A1992JY18200013 PM 1281606 ER PT J AU PRICE, BD CALDERWOOD, SK AF PRICE, BD CALDERWOOD, SK TI HEAT-INDUCED TRANSCRIPTION FROM RNA POLYMERASE-II AND POLYMERASE-III AND HSF BINDING-ACTIVITY ARE COORDINATELY REGULATED BY THE PRODUCTS OF THE HEAT-SHOCK GENES SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HSP70 GENE; PROTEIN-SYNTHESIS; DNA-BINDING; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; FACTOR CONTAINS; HUMAN-CELLS; B2 REPEATS; EXPRESSION; ACTIVATION AB Heat shock leads to co-ordinate increases in transcription of a family of heat shock genes, including the mouse hsp70.1 and B2 genes. Activation of the heat shock transcription factor (HSF) by heat shock stimulates transcription of the murine hsp70.1 gene (by RNA polymerase II). B2 genes are short, repetitive sequences whose transcription (by RNA polymerase III) are also increased after heat shock. We have studied whether heat-induced transcription is auto-regulated by the products of the heat shock genes. The results indicate: (1) after an initial heat shock, transcription of the heat shock genes by RNA polymerases II and III becomes desensitized to further heat shock, and the heat-induced DNA binding activity of the HSF is lost, (2) if accumulation of heat shock gene products is inhibited, the desensitizing effect of a prior heat shock is removed, and (3) transcription of the hsp70.1 and B2 genes apparently involves different mechanisms, with hsp70.1 employing the HSF and the B2 gene using a separate, heat-activated transcriptional mechanism. However, the level of transcription from the hsp70.1 and B2 genes and the stability of their respective RNAs are co-ordinately regulated by the level of heat shock protein in the cell. The data indicate that auto-regulation of the level of mouse heat shock gene products is mediated by RNA polymerase II transcripts but that the regulatory mechanism can control transcription from RNA polymerase III genes as well. RP PRICE, BD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,STRESS PROTEIN GRP,BOSTON,MA 02115, USA. FU NCI NIH HHS [R29CA44940]; PHS HHS [R0147407] NR 46 TC 23 Z9 23 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD NOV PY 1992 VL 153 IS 2 BP 392 EP 401 DI 10.1002/jcp.1041530219 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA JU553 UT WOS:A1992JU55300018 PM 1385451 ER PT J AU DIAMOND, R WHITE, RF MYERS, RH MASTROMAURO, C KOROSHETZ, WJ BUTTERS, N ROTHSTEIN, DM MOSS, MB VASTERLING, J AF DIAMOND, R WHITE, RF MYERS, RH MASTROMAURO, C KOROSHETZ, WJ BUTTERS, N ROTHSTEIN, DM MOSS, MB VASTERLING, J TI EVIDENCE OF PRESYMPTOMATIC COGNITIVE DECLINE IN HUNTINGTONS-DISEASE SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID MAJOR AFFECTIVE-DISORDER; NEUROPSYCHOLOGICAL DEFICITS; PSYCHIATRIC SYNDROMES; ALZHEIMERS-DISEASE; MEMORY DISORDERS; VERBAL RECALL; RISK; DEMENTIA; RECOGNITION; METABOLISM AB Asymptomatic persons at risk for Huntington's disease (HD) (N = 28) were assessed with neuropsychological, psychiatric, and neurologic tests while undergoing genetic linkage studies to determine their probability of carrying the HD gene. Those participants who were subsequently identified as probable gene carriers did not differ on neurologic or psychiatric examination from those subsequently identified as probable noncarriers. Neuropsychological data are presented for a subset of participants free of other conditions (such as alcoholism) putting them at risk for cognitive deficits. Among these subjects, probable gene carriers were inferior to probable noncarriers on the neuropsychological battery as a whole and on several individual tests involving learning and memory. The results suggest the presence of cognitive decline prior to identifiable motor impairments in HD. C1 BOSTON UNIV,SCH MED,DEPT NEUROL,80 E CONCORD ST,BOSTON,MA 02118. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. VET ADM MED CTR JAMAICA PLAIN,DEPT PSYCHOL,BOSTON,MA 02130. TUFTS UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02111. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. VET ADM MED CTR,PSYCHOL SERV,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,LA JOLLA,CA 92093. CHARLES RIVER HOSP,DEPT ADULT PSYCHOL,WELLESLEY,MA. BOSTON UNIV,SCH MED,DEPT ANAT,BOSTON,MA 02118. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02114. VET AFFAIRS MED CTR,PSYCHOL SERV,NEW ORLEANS,LA. FU NIDCD NIH HHS [DC00017]; NINDS NIH HHS [2POINS16367-06] NR 54 TC 57 Z9 57 U1 0 U2 4 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD NOV PY 1992 VL 14 IS 6 BP 961 EP 975 DI 10.1080/01688639208402547 PG 15 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA KA041 UT WOS:A1992KA04100007 PM 1452640 ER PT J AU MACAULAY, AL CULLEN, DJ AF MACAULAY, AL CULLEN, DJ TI VERIFYING THE (WE HOPE) VERIFIED - REFERENCE CHECKING IN THE JOURNAL OF CLINICAL ANESTHESIA SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material RP MACAULAY, AL (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD NOV-DEC PY 1992 VL 4 IS 6 BP 437 EP 438 DI 10.1016/0952-8180(92)90213-K PG 2 WC Anesthesiology SC Anesthesiology GA KB978 UT WOS:A1992KB97800001 PM 1457109 ER PT J AU BILLER, BMK ALEXANDER, JM ZERVAS, NT HEDLEYWHYTE, ET ARNOLD, A KLIBANSKI, A AF BILLER, BMK ALEXANDER, JM ZERVAS, NT HEDLEYWHYTE, ET ARNOLD, A KLIBANSKI, A TI CLONAL ORIGINS OF ADRENOCORTICOTROPIN-SECRETING PITUITARY TISSUE IN CUSHINGS-DISEASE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; POLYMERASE CHAIN-REACTION; TRANS-SPHENOIDAL SURGERY; X-CHROMOSOME; CANDIDATE ONCOGENE; ECTOPIC PRODUCTION; ADRENAL DISORDERS; HORMONE; ADENOMAS; TUMORS AB It is unclear whether Cushing's disease results from a primary pituitary disorder or arises in response to abnormal hypothalamic control of the pituitary gland. Clonal analysis can provide information as to whether neoplastic tissue is derived from a monoclonal proliferation of a genetically altered cell or from a polyclonal expansion of a group of cells affected by a common stimulus. We used X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase, hypoxanthine phosphoribosyltransferase, and DXS255 loci in 11 women with biochemically and pathologically confirmed Cushing's disease to determine the clonal origins of corticotroph adenomas and corticotroph hyperplasia. Tumor tissue from all 10 women with morphologically and immunohistochemically confirmed ACTH-secreting pituitary microadenomas demonstrated a monoclonal pattern. Pathologically confirmed corticotroph hyperplasia in a patient with a CRH-secreting bronchial carcinoid was found to be polyclonal. We conclude that corticotroph microadenomas in Cushing's disease are monoclonal, supporting the theory that a spontaneous somatic mutation is the primary pathogenetic mechanism in this disorder. In addition, the demonstration of polyclonality in corticotroph hyperplasia implies that excess of hypothalamic hormones is an etiologic mechanism in cases of Cushing's syndrome associated with ectopic CRH-secreting tumors. C1 MASSACHUSETTS GEN HOSP, DEPT MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROSURG, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP BILLER, BMK (reprint author), MASSACHUSETTS GEN HOSP, DEPT MED, NEUROENDOCRINE UNIT, JACKSON 10, FRUIT ST, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [DK-07028, DK-08330, DK-40947] NR 71 TC 63 Z9 64 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1992 VL 75 IS 5 BP 1303 EP 1309 DI 10.1210/jc.75.5.1303 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JX176 UT WOS:A1992JX17600024 PM 1358909 ER PT J AU KATZNELSON, L OPPENHEIM, DS COUGHLIN, JF KLIMAN, B SCHOENFELD, DA KLIBANSKI, A AF KATZNELSON, L OPPENHEIM, DS COUGHLIN, JF KLIMAN, B SCHOENFELD, DA KLIBANSKI, A TI CHRONIC SOMATOSTATIN ANALOG ADMINISTRATION IN PATIENTS WITH ALPHA-SUBUNIT-SECRETING PITUITARY-TUMORS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE; SMS 201-995; ACROMEGALIC PATIENTS; ADENOMAS; THYROTROPIN; OCTREOTIDE; SMS-201-995; RECEPTORS; INVITRO; THERAPY AB Glycoprotein hormone-producing (GPH) pituitary adenomas represent approximately 25% of all pituitary tumors. Elevated serum levels of intact GPHs or their free alpha- and beta-subunits have been demonstrated in patients with such tumors, and isolated hypersecretion of alpha-subunit has been reported to occur in 7% of patients. Somatostatin has been shown to decrease GPH subunit levels in cultured adenoma cells in vitro, and somatostatin receptors have been identified on the cell membranes of these tumors. We, therefore, investigated the effect of chronic somatostatin analog administration on hormone production and tumor size in six patients with GPH-producing macroadenomas and elevated serum alpha-subunit levels. Patients initially received native somatostatin as an iv 250-mug bolus at 0800 h, followed by a constant infusion of 2 mg over 4 h, and serum alpha-subunit concentrations were measured at 30-min intervals after baseline sampling for a total of 9 h. Patients then received a somatostatin analog, octreotide (100 mug, twice daily, sc) for 8 weeks. Serum alpha-subunit levels were determined weekly at 30-min intervals before and for 4 h after the 0800 h octreotide dose. Pituitary magnetic resonance imaging scans and visual field testing were assessed before and after the study. During the 4-h somatostatin infusion, four patients had a significant decrease in alpha-subunit levels (P < 0.05). During the 8-week chronic octreotide administration period, two patients had significant decreases in alpha-subunit levels of 34.6% and 26.7% (P = 0.03 and 0.01, respectively). One of these two patients had a small reduction in tumor size. Two patients whose serum alpha-subunit level did not significantly change while receiving octreotide had a reduction in tumor size or definite improvement in visual field abnormalities. Three patients received a maximum octreotide dose of 250 mug, three times daily. In one patient, there was a significant decrease in alpha-subunit levels by 45% (P = 0.0001) in association with a marked improvement in visual field abnormalities. In another such patient, continued administration of octreotide to a maximum dose of 250 mug, three times daily, was associated with a marked reduction in tumor size. Of the four patients who demonstrated significant decreases in alpha-subunit concentrations during the initial somatostatin infusion, three patients had a significant reduction in alpha-subunit levels while receiving octreotide. One patient who did not have a decrease in alpha-subunit levels during the somatostatin infusion demonstrated a small decrease in tumor size during higher dose octreotide treatment. We observed decreases in tumor size and/or visual field abnormalities in a small group of patients with GPH-producing adenomas and elevated serum alpha-subunit levels during chronic octreotide administration. Serum alpha-subunit levels may also be decreased by octreotide, but changes in hormone levels may not parallel changes in tumor size. Further studies are required to determine whether a somatostatin analog may be useful as adjuvant medical therapy for a subset of patients with GPH-producing pituitary adenomas. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED, NEUROENDOCRINE UNIT,JACKSON 10,32 FRUIT ST, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, GEN CLIN RES CTR, BOSTON, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NIDDK NIH HHS [DK-07028, DK-40947] NR 43 TC 49 Z9 49 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1992 VL 75 IS 5 BP 1318 EP 1325 DI 10.1210/jc.75.5.1318 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA JX176 UT WOS:A1992JX17600026 PM 1358910 ER PT J AU FREBOURG, T FRIEND, SH AF FREBOURG, T FRIEND, SH TI CANCER RISKS FROM GERMLINE P53 MUTATIONS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID WILD-TYPE P53; LI-FRAUMENI SYNDROME; GENE; GROWTH; CELLS; SUPPRESSOR; ONCOGENE; PROTEIN; FAMILY; TRANSFORMATION C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. RP FREBOURG, T (reprint author), MASSACHUSETTS GEN HOSP E,CTR CANC,DIV MOLEC GENET,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 45 TC 70 Z9 70 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1992 VL 90 IS 5 BP 1637 EP 1641 DI 10.1172/JCI116034 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JZ475 UT WOS:A1992JZ47500001 PM 1430194 ER PT J AU GORN, AH LIN, HY YAMIN, M AURON, PE FLANNERY, MR TAPP, DR MANNING, CA LODISH, HF KRANE, SM GOLDRING, SR AF GORN, AH LIN, HY YAMIN, M AURON, PE FLANNERY, MR TAPP, DR MANNING, CA LODISH, HF KRANE, SM GOLDRING, SR TI CLONING, CHARACTERIZATION, AND EXPRESSION OF A HUMAN CALCITONIN RECEPTOR FROM AN OVARIAN-CARCINOMA CELL-LINE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE OSTEOCLAST; CAMP; G-PROTEIN; GIANT CELL TUMOR OF BONE; PARATHYROID HORMONE RECEPTOR; SECRETIN RECEPTOR ID GENE-RELATED PEPTIDE; CALCIUM-REGULATING HORMONES; PARATHYROID-HORMONE; ADENYLATE-CYCLASE; MOLECULAR-CLONING; LIGAND-BINDING; G-PROTEINS; SEQUENCE; SITES; RAT AB A human ovarian small cell carcinoma line (BIN-67) expresses abundant calcitonin (cT) receptors (CTR) (143,000 per cell) that are coupled, to adenylate cyclase. The dissociation constants (K(d)) for the CTRs on these BIN-67 cells is approximately 0.42 nM for salmon CT and approximately 4.6 nM for human CT. To clone a human CTR (hCTR), a BIN-67 cDNA library was screened using a cDNA probe from a porcine renal CTR (pCTR) that we recently cloned. One positive clone of 3,588 bp was identified. Transfection of this cDNA into COS cells resulted in expression of receptors with high affinity for salmon CT (K(d) = approximately 0.44 nM) and for human CT (K(d) = approximately 5.4 nM). The expressed hCTR was coupled to adenylate cyclase. Northern analysis with the hCTR cDNA probe indicated a single transcript of approximately 4.2 kb. The cloned cDNA encodes a putative peptide of 490 amino acids with seven potential transmembrane domains. The amino acid sequence of the hCTR is 73% identical to the pCTR, although the hCTR contains an insert of 16 amino acids between transmembrane domain I and II. The structural differences may account for observed differences in binding affinity between the porcine renal and human ovarian CTRs. The CTRs are closely related to the receptors for parathyroid hormone-parathyroid hormone-related peptide and secretin; these receptors comprise a distinct family of G protein-coupled seven transmembrane domain receptors. Interestingly, the hCTR sequence is remotely related to the cAMP receptor of Dictyostelium discoideum (21% identical), but is not significantly related to other G protein-coupled receptor sequences now in the data bases. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV,ARTHRIT UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,DEPT MED,BOSTON,MA 02215. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. FU NIAID NIH HHS [AI-27850]; NIAMS NIH HHS [AR-03564, AR-07258] NR 58 TC 179 Z9 182 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1992 VL 90 IS 5 BP 1726 EP 1735 DI 10.1172/JCI116046 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JZ475 UT WOS:A1992JZ47500013 PM 1331173 ER PT J AU SAAD, MJA ARAKI, E MIRALPEIX, M ROTHENBERG, PL WHITE, MF KAHN, CR AF SAAD, MJA ARAKI, E MIRALPEIX, M ROTHENBERG, PL WHITE, MF KAHN, CR TI REGULATION OF INSULIN-RECEPTOR SUBSTRATE-1 IN LIVER AND MUSCLE OF ANIMAL-MODELS OF INSULIN RESISTANCE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE DIABETES; FASTING; INSULIN RESISTANCE; INSULIN RECEPTOR KINASE; INSULIN RECEPTOR SUBSTRATE; OBESITY ID TYROSINE KINASE-ACTIVITY; EPIDERMAL GROWTH-FACTOR; SKELETAL-MUSCLE; DIABETIC RATS; ENDOGENOUS SUBSTRATE; FACTOR-I; BINDING; PHOSPHORYLATION; AUTOPHOSPHORYLATION; PROTEINS AB Insulin rapidly stimulates tyrosine phosphorylation of a protein of approximately 185 kD in most cell types. This protein, termed insulin receptor substrate-1 (IRS-1), has been implicated in insulin signal transmission based on studies with insulin receptor mutants. In the present study we have examined the levels of IRS-1 and the phosphorylation state of insulin receptor and IRS-1 in liver and muscle after insulin stimulation in vivo in two rat models of insulin resistance, i.e., insulinopenic diabetes and fasting, and a mouse model of non-insulin-dependent diabetes mellitus (ob/ob) by immunoblotting with anti-peptide antibodies to IRS-1 and anti-phosphotyrosine antibodies. As previously described, there was an increase in insulin binding and a parallel increase in insulin-stimulated receptor phosphorylation in muscle of fasting and streptozotocin-induced (STZ) diabetic rats. There was also a modest increase in overall receptor phosphorylation in liver in these two models, but when normalized for the increase in binding, receptor phosphorylation was decreased, in liver and muscle of STZ diabetes and in liver of 72 h fasted rats. In the hyperinsulinemic ob/ob mouse there was a decrease in insulin binding and receptor phosphorylation in both liver and muscle. The tyrosyl phosphorylation of IRS-1 after insulin stimulation reflected an amplification of the receptor phosphorylation in liver and muscle of hypoinsulinemic animals (fasting and STZ diabetes) with a twofold increase, and showed a significant reduction (approximately 50%) in liver and muscle of ob/ob mouse. By contrast, the levels of IRS-1 protein showed a tissue specific regulation with a decreased level in muscle and an increased level in liver in hypoinsulinemic states of insulin resistance, and decreased levels in liver in the hyperinsulinemic ob/ob mouse. These data indicate that: (a) IRS-1 protein levels are differentially regulated in liver and muscle; (b) insulin levels may play a role in this differential regulation of IRS-1; (c) IRS-1 phosphorylation depends more on insulin receptor kinase activity than IRS-1 protein levels; and (d) reduced IRS-1 phosphorylation in liver and muscle may play a role in insulin-resistant states, especially of the ob/ob mice. C1 BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. FU NIDDK NIH HHS [DK-33201, DK-36836] NR 47 TC 268 Z9 273 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1992 VL 90 IS 5 BP 1839 EP 1849 DI 10.1172/JCI116060 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA JZ475 UT WOS:A1992JZ47500027 PM 1331176 ER PT J AU BOURBEAU, P MCGOUGH, DA FRASER, H SHAH, N RINALDI, MG AF BOURBEAU, P MCGOUGH, DA FRASER, H SHAH, N RINALDI, MG TI FATAL DISSEMINATED INFECTION CAUSED BY MYCELIOPHTHORA-THERMOPHILA, A NEW AGENT OF MYCOSIS - CASE-HISTORY AND LABORATORY CHARACTERISTICS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note AB We report a case of human infection caused by the hyphomycete Myceliophthora thermophila. A 7-year-old male with neurofibromatosis (type 1) was diagnosed in 1987 with acute myeloblastic leukemia associated with the chromosomal abnormality monosomy 7. The patient experienced multiple serious infections over a three-year period before expiring in 1990 while in the end stage of leukemia. Autopsy findings included fungal vegetations of the left atrium, ascending aorta, and pulmonary arteries and fungal invasion of both lungs. Cultures yielded M. thermophila. We believe that this is the first reported fatality caused by M. thermophila. C1 GEISINGER MED CTR,DEPT PEDIAT HEMATOL ONCOL,DANVILLE,PA 17822. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,FUNGUS TESTING LAB,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT VET AFFAIRS MYCOL,REFERENCE LAB,SAN ANTONIO,TX 78284. RP BOURBEAU, P (reprint author), GEISINGER MED CTR,DEPT LAB MED,DANVILLE,PA 17822, USA. NR 14 TC 19 Z9 19 U1 0 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 NOV PY 1992 VL 30 IS 11 BP 3019 EP 3023 PG 5 WC Microbiology SC Microbiology GA JU856 UT WOS:A1992JU85600054 PM 1452676 ER PT J AU SHAPIRO, CL MAUCH, PM AF SHAPIRO, CL MAUCH, PM TI RADIATION-ASSOCIATED BREAST-CANCER AFTER HODGKINS-DISEASE - RISKS AND SCREENING IN PERSPECTIVE SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID OPPOSITE BREAST; 2ND CANCERS; WOMEN; AGE; IRRADIATION; TUBERCULOSIS; RADIOTHERAPY; MAMMOGRAPHY; CARCINOMA; BIOPSY C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP SHAPIRO, CL (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115, USA. NR 36 TC 23 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1992 VL 10 IS 11 BP 1662 EP 1665 PG 4 WC Oncology SC Oncology GA JV900 UT WOS:A1992JV90000002 PM 1403048 ER PT J AU BLAKE, DD COOK, JD KEANE, TM AF BLAKE, DD COOK, JD KEANE, TM TI POSTTRAUMATIC-STRESS-DISORDER AND COPING IN VETERANS WHO ARE SEEKING MEDICAL-TREATMENT SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article ID COGNITIVE APPRAISAL; VIETNAM VETERANS; WAR; DEPRESSION AB The present study examined psychological coping styles and mental health treatment histories in veterans with PTSD. This study also served as a replication and extension of an earlier investigation that assessed the prevalence of PTSD in World War II, Korea, and Vietnam combat veterans who were seeking medical treatment. Thirty-six combat veteran medical patients were compared to 38 war-era controls. Nearly a third of the combat veterans met psychometric criteria for PTSD; none of the controls met these criteria. Both PTSD-positive subjects and mental health treatment seekers showed a significantly greater use of emotion-focused coping. Results also showed that Vietnam combatants were more likely to have received individual mental health treatment. These findings and their treatment implications are discussed. C1 VET ADM MED CTR JAMAICA PLAIN,NATL CTR PTSD,BOSTON,MA 02130. TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. NR 32 TC 52 Z9 52 U1 1 U2 4 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 NOV PY 1992 VL 48 IS 6 BP 695 EP 704 DI 10.1002/1097-4679(199211)48:6<695::AID-JCLP2270480602>3.0.CO;2-P PG 10 WC Psychology, Clinical SC Psychology GA JZ527 UT WOS:A1992JZ52700001 PM 1452757 ER PT J AU BHALLA, M THOMPSON, BG HARLEY, RA MCLOUD, TC AF BHALLA, M THOMPSON, BG HARLEY, RA MCLOUD, TC TI PRIMARY EXTRAOSSEOUS PULMONARY OSTEOGENIC-SARCOMA - CT FINDINGS SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE SARCOMA; LUNGS; NEOPLASMS; COMPUTED TOMOGRAPHY AB This is a report of a primary extraosseous osteogenic sarcoma of the lung. The patient presented with fever and productive cough. Chest radiography and CT showed a cavitary lesion with an air-fluid level. The lesion was treated as an abscess. Despite aggressive antibiotic therapy and drainage, the patient continued to deteriorate rapidly. At autopsy the lesion was found to be a primary extraosseous pulmonary osteogenic sarcoma. C1 MED UNIV S CAROLINA,DEPT PATHOL,CHARLESTON,SC 29425. RP BHALLA, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 1992 VL 16 IS 6 BP 974 EP 976 DI 10.1097/00004728-199211000-00027 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JY187 UT WOS:A1992JY18700027 PM 1430451 ER PT J AU MARGOLIS, HC MORENO, EC AF MARGOLIS, HC MORENO, EC TI COMPOSITION OF POOLED PLAQUE FLUID FROM CARIES-FREE AND CARIES-POSITIVE INDIVIDUALS FOLLOWING SUCROSE EXPOSURE SO JOURNAL OF DENTAL RESEARCH LA English DT Article ID HUMAN DENTAL PLAQUE; AMINO-ACID PROFILES; SUSCEPTIBLE INDIVIDUALS; PH; CALCIUM; SALIVA; INSITU; ENAMEL; PHOSPHATE AB The composition of pooled plaque fluid from five population samples was determined before and at selected times (7, 15, 30, and 60 min) after a 10% sucrose rinse. Subjects were grouped according to caries status (caries-free, CF, DMFS = 0; caries-positive, CP, DMFS > 10). Samples were also studied from white-spot surfaces and from sound surfaces of the same mouths of two additional CP groups. Plaque fluid was isolated by centrifugation and analyzed for organic acids, inorganic ions (ion chromatography), and pH (microelectrodes). Prior to sucrose exposure, plaque fluids from the CF subgroups and from sound surfaces of the CP subjects had higher pH values than samples from CP subgroups and from white-spot surfaces, respectively; the ionic compositions were otherwise similar. Starved plaque fluids were also found to be supersaturated with respect to enamel and to a significantly greater degree in the CF samples, suggesting that CF plaque fluid may have a greater remineralization potential than CP samples. Following sucrose exposure, a rapid decrease in plaque fluid pH was observed, which corresponded primarily to lactic acid production. For all times examined, mean pH and DS(En) values were lower and lactic acid concentrations were higher in the CP samples than in the CF samples; noted differences were statistically significant at 7 min for pH and DS(En), and at 7, 15, and 30 min for lactic acid. Lower values of DS(En) suggest that plaque fluid from CP subjects had a measurably greater cariogenic potential. Calcium concentrations also increased in plaque fluid, following sucrose exposure, and to similar levels in samples from CF and CP subjects, despite significantly lower acid production in the CF samples. These latter results appear to be associated with the further finding that whole plaque from the CF subgroups contained significantly more calcium than the samples from the CP subjects. The availability of mineral ions like calcium within plaque may, therefore, play an important role in controlling enamel demineralization. RP MARGOLIS, HC (reprint author), FORSYTH DENT CTR,140 THE FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-07009, DE-03187, DE-07493] NR 32 TC 82 Z9 85 U1 0 U2 1 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 1992 VL 71 IS 11 BP 1776 EP 1784 DI 10.1177/00220345920710110301 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JW896 UT WOS:A1992JW89600003 PM 1401439 ER PT J AU AOBA, T SHIMODA, S MORENO, EC AF AOBA, T SHIMODA, S MORENO, EC TI LABILE OR SURFACE POOLS OF MAGNESIUM, SODIUM, AND POTASSIUM IN DEVELOPING PORCINE ENAMEL MINERAL SO JOURNAL OF DENTAL RESEARCH LA English DT Article ID INCISOR ENAMEL; RAT INCISOR; CALCIUM; AMELOGENESIS; CRYSTALLIZATION; HYDROXYAPATITE; FLUID AB The present study was undertaken to assess the labile or surface pools of Mg, Na, and K ions in porcine enamel tissues at various developmental stages. The enamel samples, corresponding to the outer and the inner secretory, the early maturing, and the mature hard enamel, were dissected from the labial sides of permanent incisors of 6- to 8-month-old piglets. Each enamel sample was extracted successively with solutions of de-ionized water and 50 mmol/L Tris-4 mol/L guanidine buffer (for removal of organic matrix proteins, mainly amelogenins). The labile (free or organically bound) pools of Mg, Na, and K were assessed by the total amounts of these ionic species extracted by the water and Tris-guanidine buffer. The surface (adsorbed onto enamel mineral) pool of Mg was assessed directly by determination of the adsorption of Mg onto enamel mineral at various developmental stages. The results showed that: (i) 30-40% of the Mg in the secretory and early maturation enamel was in the surface pool (adsorbed onto the enamel mineral); (ii) 25 to 40% of the total sodium in the enamel samples was in labile forms; and (iii) most (around 70-80%) of the total potassium was readily extracted in water and appeared to originate from the enamel fluid; only marginal portions remained in the solids. The present adsorption studies also indicated that the maximum uptake of magnesium in the early maturation enamel was due mostly to an increase of the occupancy by Mg ions of adsorption sites on the crystal surfaces, which become accessible with a massive removal of enamel matrix proteins. The observation that the surface pool of Mg (and the total Mg content) decreased markedly with the advancement of mineralization is explained by the displacement of the adsorbed Mg from the crystal surfaces by Ca2+ having a higher adsorption affinity for the same adsorption sites and by changes in the properties of the mineral surfaces. The overall results support the contention that incorporation of Mg into developing enamel upon resorption of the organic matrix may play a key role in regulating enamel crystal growth. C1 TSURUMI UNIV,FAC DENT,YOKOHAMA,KANAGAWA,JAPAN. RP AOBA, T (reprint author), FORSYTH DENT CTR,140 THE FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE03187, DE08670] NR 29 TC 15 Z9 15 U1 0 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 1992 VL 71 IS 11 BP 1826 EP 1831 DI 10.1177/00220345920710111201 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JW896 UT WOS:A1992JW89600012 PM 1401446 ER PT J AU BROWN, D SABOLIC, I GLUCK, S AF BROWN, D SABOLIC, I GLUCK, S TI POLARIZED TARGETING OF V-ATPASE IN KIDNEY EPITHELIAL-CELLS SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE PROTON PUMPS; COLLECTING DUCT; IMMUNOCYTOCHEMISTRY; MICROTUBULES; KIDNEY ID MEDULLARY COLLECTING DUCT; VACUOLAR H+-ATPASE; INTERCALATED CELLS; TURTLE-BLADDER; BOVINE KIDNEY; RAT-KIDNEY; BRUSH-BORDER; BICARBONATE SECRETION; EXOCYTOTIC INSERTION; LUMINAL MEMBRANE AB The membrane-associated V-ATPase that plays an important role in the regulation of acid-base balance by the kidney is a multisubunit enzyme that is densely packed into specialized membrane domains in intercalated cells. Intercalated cells can be separated into at least two subtypes, A-cells and B-cells, based on their morphological features, the distribution of V-ATPase, and the presence or absence of a basolateral chloride/bicarbonate anion exchanger (AE1) exclusively in B-cells. A-cells secrete protons into the tubule lumen, whereas B-cells secrete bicarbonate. The relative amounts of V-ATPase and AE1 in the plasma membranes of A- and B-cells are modulated under different acid-base conditions and provide a sensitive means by which urinary acidification can be controlled. The mechanisms governing the movement of acid-base transporting proteins between intracellular vesicles and the plasma membrane are under investigation. The microtubular apparatus of the cell is involved in maintaining both apical and basolateral polarity of the enzyme, and different isoforms of V-ATPase subunits may also be involved in the selective targeting of V-ATPase to different membrane domains. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. JEWISH HOSP ST LOUIS,DIV RENAL,ST LOUIS,MO 63110. JEWISH HOSP ST LOUIS,DEPT MED,ST LOUIS,MO 63110. JEWISH HOSP ST LOUIS,DEPT CELL BIOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. NR 51 TC 47 Z9 48 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 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD NOV PY 1992 VL 172 BP 231 EP 243 PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA KF720 UT WOS:A1992KF72000021 PM 1491226 ER PT J AU BIRKENBACH, M XIAO, T BRADBURY, LE TEDDER, TF KIEFF, E AF BIRKENBACH, M XIAO, T BRADBURY, LE TEDDER, TF KIEFF, E TI CHARACTERIZATION OF AN EPSTEIN-BARR-VIRUS RECEPTOR ON HUMAN EPITHELIAL-CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN LYMPHOCYTES-B; COMPLEMENT RECEPTOR; ANTIPROLIFERATIVE ANTIBODY; MEMBRANE-PROTEIN; LIGAND-BINDING; CR-2; ANTIGEN; C3D; IDENTIFICATION; TYPE-2 AB Epstein-Barr virus (EBV) adsorption to human B lymphocytes is mediated by the viral envelope glycoprotein, gp350/220, which binds to the cell surface protein, CD21, also known as the CR2 complement receptor. Human epithelial cells also express an EBV receptor. A candidate surface molecule of 195 kD has previously been identified on an epithelial cell line and explanted epithelial tissue by reactivity with the CD21 specific monoclonal antibody (mAb), HB-5a. In experiments to further characterize the epithelial cell EBV receptor, we have found that two human epithelial cell lines, RHEK-1 and HeLa, specifically bind intact EB virions. A 145-kD protein, similar in size to B lymphocyte CD21, was specifically precipitated from surface iodinated RHEK-1 cells using the HB-5a mAb, or using purified soluble gp350/220 coupled to agarose beads. The previously identified 195-kD protein did not bind to gp350/220 or react with two other anti-CD21 mAbs. CD21 homologous RNA, similar in size to the B lymphocyte CD21 mRNA, was detected in both RHEK-1 and HeLa cells. The nucleotide sequence of the epithelial cell cDNA was identical to B lymphocyte CD21. The longest clone differs from previously reported CD21 cDNAs in having additional 5' untranslated sequence. Polymerase chain reaction amplification of RHEK-1- or B lymphoblastoid-derived cDNA verified that most CD21 transcripts are initiated at least 30-50 nucleotides upstream of the previously reported mRNA cap site. These experiments demonstrate that human epithelial cells can express CD21, and that CD21 is likely to mediate EBV adsorption to epithelial cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA-00449, K11CA01341]; NIAID NIH HHS [AI-26872] NR 51 TC 70 Z9 75 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1992 VL 176 IS 5 BP 1405 EP 1414 DI 10.1084/jem.176.5.1405 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JV012 UT WOS:A1992JV01200020 PM 1383386 ER PT J AU STAUNTON, DE OCKENHOUSE, CF SPRINGER, TA AF STAUNTON, DE OCKENHOUSE, CF SPRINGER, TA TI SOLUBLE INTERCELLULAR-ADHESION MOLECULE 1-IMMUNOGLOBULIN-G1 IMMUNOADHESIN MEDIATES PHAGOCYTOSIS OF MALARIA-INFECTED ERYTHROCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID PLASMODIUM-FALCIPARUM; ICAM-1 CD54; RECEPTOR; LFA-1; BINDING; MAC-1; LIGAND AB We describe an immunoadhesin molecule containing intercellular adhesion molecule 1 (ICAM-1) molecularly fused to hinge and C(H)2 and C(H)3 domains of the human immunoglobulin G1 H chain that binds Plasmodium falciparum-infected erythrocytes. This receptor-based immunoadhesin is an effective and specific inhibitor of P. falciparum-infected erythrocyte adhesion to ICAM-1-bearing surfaces, but does not inhibit leukocyte function antigen 1 (LFA-1) interaction with ICAM-1. Furthermore, the immunoadhesin promotes phagocytosis and destruction of parasitized erythrocytes by human monocytes. Each of these modes of action has potential for the therapy of malaria. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. WALTER REED ARMY MED CTR,DEPT MED,WASHINGTON,DC 20307. RP STAUNTON, DE (reprint author), CTR BLOOD RES,EQRF,200 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 22 TC 28 Z9 28 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1992 VL 176 IS 5 BP 1471 EP 1476 DI 10.1084/jem.176.5.1471 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA JV012 UT WOS:A1992JV01200029 PM 1383388 ER PT J AU SEILER, JG BARNES, K GELBERMAN, RH CHALIDAPONG, P AF SEILER, JG BARNES, K GELBERMAN, RH CHALIDAPONG, P TI ENDOSCOPIC CARPAL-TUNNEL RELEASE - AN ANATOMIC STUDY OF THE 2-INCISION METHOD IN HUMAN CADAVERS SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB To determine the relationship of neurovascular structures to the sites of portal placement and transverse carpal ligament division during two-portal endoscopic carpal tunnel release, a study of 20 fresh cadaver specimens was carried out. Open dissection of the carpal tunnel after endoscopic surgery showed complete ligamentous release in 18 hands (90 %). In 10 specimens, the procedure was performed as described by Chow. There was one partial transection of the superficial palmar arch (5 %), and five specimens (50 %) had complete divisions of the superficial palmar fascia with considerable pressure placed on the ulnar nerve at the wrist. A modified technique was used in 10 specimens in which the proximal incision was made in a more distal location and a distally based ligamentous flap was created. The superficial palmar arch and the distal edge of the transverse carpal ligament were visualized directly before passage of the trocar. No complications were noted with this method. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,WACC-527,BOSTON,MA 02114. NR 0 TC 49 Z9 51 U1 2 U2 3 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 1992 VL 17A IS 6 BP 996 EP 1002 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA JX315 UT WOS:A1992JX31500003 PM 1430965 ER PT J AU GRAFF, SN SEILER, JG JUPITER, JB AF GRAFF, SN SEILER, JG JUPITER, JB TI ACUTE GOUT AFTER CARPAL-TUNNEL RELEASE SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB A carpal tunnel release was performed on three patients with known gout of the lower extremity but not of the upper extremity. Each patient had a postoperative inflammatory reaction in a treated hand, and there was some suspicion of an infection in two patients. However, the inflammatory reaction resolved only when treated with a combination of anti-inflammatory and antigout medication. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 7 Z9 8 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 1992 VL 17A IS 6 BP 1031 EP 1032 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA JX315 UT WOS:A1992JX31500012 PM 1430931 ER PT J AU LUKASH, FN GREENBERG, BM GALLICO, GG PANDA, M MAY, JW AF LUKASH, FN GREENBERG, BM GALLICO, GG PANDA, M MAY, JW TI A SOCIOECONOMIC ANALYSIS OF DIGITAL REPLANTATIONS RESULTING FROM HOME USE OF POWER TOOLS SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB Forty-seven digits in 21 patients who sustained partial or complete amputations from the home use of power tools were replanted or revascularized during a 1-year period. This represented 69% of the microvascular surgery performed for hand injuries during that year. The cost of repairing an average of 2.4 digits was $7000 (surgeon's fee) plus $697 per hour (operating room fee), as per fiscal year 1987. Postoperative hospitalization averaged 15 days at a cost of $15,679. Hand rehabilitation averaged 8 months at a cost of $3348. Fifty-four percent of the patients had no insurance. Fourteen of 21 patients (67%) required at least one additional procedure. Two patients had to make a career change after the injury. The majority of patients with digital replantations were dissatisfied with the emotional costs and the number of subsequent operations. Lack of patient and family awareness of the length of the rehabilitative period was particularly evident. C1 MASSACHUSETTS GEN HOSP,DIV PLAST & RECONSTRUCT SURG,BOSTON,MA 02114. NR 0 TC 7 Z9 7 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 1992 VL 17A IS 6 BP 1042 EP 1044 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA JX315 UT WOS:A1992JX31500015 PM 1430934 ER PT J AU RIVES, K GELBERMAN, R SMITH, B CARNEY, K AF RIVES, K GELBERMAN, R SMITH, B CARNEY, K TI SEVERE CONTRACTURES OF THE PROXIMAL INTERPHALANGEAL JOINT IN DUPUYTRENS DISEASE - RESULTS OF A PROSPECTIVE TRIAL OF OPERATIVE CORRECTION AND DYNAMIC EXTENSION SPLINTING SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB In a prospective study, 23 proximal interphalangeal joints that were severely contracted (greater-than-or-equal-to 45 degrees) as a result of Dupuytren's disease underwent operative correction and 6 months of dynamic extension splinting. Proximal interphalangeal joint extension was measured preoperatively and postoperatively at 3-month intervals for 1 year and at 6-month intervals thereafter. Mean follow-up was 2 years (minimum, 1 year). Overall, at 2 years, 44% improvement in proximal interphalangeal joint extension was noted. Mean improvement of 59% in proximal interphalangeal joint extension was noted in patients who complied with the postoperative dynamic extension splinting program. Patients who were noncomplaint demonstrated a 25% improvement in proximal interphalangeal joint extension. The difference in values between patients who were compliant and those who were not was statistically significant. Other factors-severity of contracture, digit involved, and the necessity for capsular release-were not significantly related to outcome. This study suggests that soft tissue responds to continuous dynamic extension stresses and can be remodeled over time. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,WACC-527,BOSTON,MA 02114. NR 0 TC 27 Z9 27 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 1992 VL 17A IS 6 BP 1153 EP 1159 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA JX315 UT WOS:A1992JX31500042 PM 1430959 ER PT J AU BRADBURY, LE KANSAS, GS LEVY, S EVANS, RL TEDDER, TF AF BRADBURY, LE KANSAS, GS LEVY, S EVANS, RL TEDDER, TF TI THE CD19/CD21 SIGNAL TRANSDUCING COMPLEX OF HUMAN LYMPHOCYTES-B INCLUDES THE TARGET OF ANTIPROLIFERATIVE ANTIBODY-1 AND LEU-13 MOLECULES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPSTEIN-BARR VIRUS; ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL AGGREGATION; C3D RECEPTOR CR-2; MONOCLONAL-ANTIBODY; ENDOTHELIAL-CELLS; SURFACE-ANTIGEN; CD19 ANTIGEN; MEMBRANE IGM; ACTIVATION AB CD19 is a member of the Ig superfamily expressed on the surface of B lymphocytes that may be involved in the regulation of B cell function. Immunoprecipitation studies with B cell lines solubilized by digitonin have shown CD19 to be part of a multimolecular complex that includes CD21 (CR2) and other unidentified proteins. In this study, two of the CD19-associated proteins were identified as TAPA-1, which is expressed on most cell types, and Leu-13, which is expressed on subsets of lymphoid cells. TAPA-1 and Leu-13 are physically associated in many cell lineages. CD19 and CD21 mAb each specifically coprecipitated proteins of the same size as those precipitated by TAPA-1 and Leu-13 mAb from B cell lines and cDNA-transfected K562 cell lines. Western blot analysis with a TAPA-1 mAb verified the identity of TAPA-1 in CD19 and CD21 immunoprecipitated materials. In addition, when TAPA-1 or Leu-13 were crosslinked and patched on the cell surface, all of the CD19 comigrated with TAPA-1 and some of the CD19 comigrated with Leu-13. Furthermore, mAb binding to CD19, CD21, TAPA-1, and Leu-13 on B cell lines induced similar biologic responses, including the induction of homotypic adhesion, inhibition of proliferation, and an augmentation of the increase in intracellular [Ca2+] induced by suboptimal cross-linking of surface Ig on B cell lines. Together, these data suggest that TAPA-1 and Leu-13 are broadly expressed members of a signal transduction complex in which lineage-specific proteins, such as CD19 and CD21, provide cell-specific functions. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. STANFORD UNIV,MED CTR,SCH MED,DEPT MED ONCOL,STANFORD,CA 94305. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,CTR CANC CELL,DEPT MOLEC IMMUNOL,BUFFALO,NY 14263. FU NCI NIH HHS [CA-34183, CA-54464]; NIAID NIH HHS [AI-26872] NR 59 TC 327 Z9 333 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1992 VL 149 IS 9 BP 2841 EP 2850 PG 10 WC Immunology SC Immunology GA JU748 UT WOS:A1992JU74800001 PM 1383329 ER PT J AU JASSOY, C JOHNSON, RP NAVIA, BA WORTH, J WALKER, BD AF JASSOY, C JOHNSON, RP NAVIA, BA WORTH, J WALKER, BD TI DETECTION OF A VIGOROUS HIV-1-SPECIFIC CYTOTOXIC LYMPHOCYTE-T RESPONSE IN CEREBROSPINAL-FLUID FROM INFECTED PERSONS WITH AIDS DEMENTIA COMPLEX SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; RECOMBINANT VACCINIA VIRUS; CENTRAL NERVOUS-SYSTEM; HIV-1 NEF PROTEIN; SEROPOSITIVE INDIVIDUALS; SYNTHETIC PEPTIDES; FINE SPECIFICITY; FRONTAL-CORTEX; III INFECTION AB AIDS dementia complex is a common neurologic disorder in later stages of HIV-1 infection. Because virus-specific CTL have been shown to contribute to neurologic disease in certain viral illnesses, we examined the cerebrospinal fluid of HIV-1-infected persons with various stages of AIDS dementia complex for the presence of HIV-1-specific CTL. In five of six subjects studied, HIV-1-specific CTL were identified in the cerebrospinal fluid. These CTL were directed at epitopes within the gag, reverse transcriptase, envelope, and nef proteins and restricted by HLA class I Ag. In four of these subjects, virus-specific CTL were detected in higher numbers in the cerebrospinal fluid compared to the peripheral blood, suggesting a specific recruitment to or local induction within the nervous system. These studies demonstrate the presence of a vigorous and broadly directed CTL response to HIV-1 in the central nervous system of infected persons with AIDS dementia complex, and provide immunologic evidence of localized intrathecal infection. Although HIV-1-specific CTL may serve to inhibit viral replication in the central nervous system, the presence of a persistent CTL response in the central nervous system may also contribute to the neurologic disorders characteristic of HIV-1 infection. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,INFECT DIS UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NIAID NIH HHS [AI30914, AI28568, AI26463] NR 68 TC 97 Z9 97 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1992 VL 149 IS 9 BP 3113 EP 3119 PG 7 WC Immunology SC Immunology GA JU748 UT WOS:A1992JU74800039 PM 1383338 ER PT J AU JOHNSON, VA MERRILL, DP CHOU, TC HIRSCH, MS AF JOHNSON, VA MERRILL, DP CHOU, TC HIRSCH, MS TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1 (HIV-1) INHIBITORY INTERACTIONS BETWEEN PROTEASE INHIBITOR RO 31-8959 AND ZIDOVUDINE, 2',3'-DIDEOXYCYTIDINE, OR RECOMBINANT INTERFERON-ALPHA-A AGAINST ZIDOVUDINE-SENSITIVE OR ZIDOVUDINE-RESISTANT HIV-1 INVITRO SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID REPLICATION AB Protease inhibitor Ro 31-8959, a compound that interrupts human immunodeficiency virus (HIV)-specific formation of infectious virions, was evaluated in two-drug combined regimens with zidovudine, 2,3-dideoxycytidine (ddC), or recombinant interferon-alphaA (rIFN-alphaA) against HIV-1 replication in vitro. By using peripheral blood mononuclear cells infected with HIV-1, drug interactions were evaluated by the median-effect principle and the isobologram technique. A zidovudine-sensitive and -resistant HIV-1 isolate pair was studied. Additive to synergistic anti-HIV-1 interactions were seen with 7.5-30 nM Ro 31-8959 and 0.005-0.02 muM zidovudine (for the zidovudine-sensitive HIV-1 isolate), 0.25-1.0 muM zidovudine (for the zidovudine-resistant HIV-1 isolate), 0.025-0.1 muM ddC, and 8-32 units/mL rIFN-alphaA, without additive toxicity. Phase I/II clinical trials of Ro 31-8959 for therapy of HIV-1 infection are in progress. If results are favorable, combined regimens including Ro 31-8959 deserve consideration for future clinical trials. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MEM SLOAN KETTERING CANC CTR,BIOCHEM PHARMACOL LAB,NEW YORK,NY 10021. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NCI NIH HHS [CA-35020, CA-12464, CA-54741] NR 15 TC 74 Z9 74 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 1992 VL 166 IS 5 BP 1143 EP 1146 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA JV015 UT WOS:A1992JV01500026 PM 1328402 ER PT J AU BLANK, IH AF BLANK, IH TI INDUSTRY-FUNDED DERMATOLOGICAL RESEARCH WITHIN ACADEMIA IN THE UNITED-STATES - FISCAL AND ETHICAL CONSIDERATIONS - REPLY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter RP BLANK, IH (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,DEPT DERMATOL,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1992 VL 99 IS 5 BP 664 EP 665 DI 10.1111/1523-1747.ep12668167 PG 2 WC Dermatology SC Dermatology GA JW928 UT WOS:A1992JW92800027 ER PT J AU GRABBE, S BRUVERS, S GRANSTEIN, RD AF GRABBE, S BRUVERS, S GRANSTEIN, RD TI EFFECTS OF IMMUNOMODULATORY CYTOKINES ON THE PRESENTATION OF TUMOR-ASSOCIATED ANTIGENS BY EPIDERMAL LANGERHANS CELLS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL WORKSHOP ON LANGERHANS CELLS CY DEC 05-06, 1991 CL DALLAS, TX ID COLONY-STIMULATING FACTOR; IMMUNOSTIMULATORY DENDRITIC CELLS; PROTEIN ANTIGENS; PRESENTING CELLS; INTERLEUKIN-1; EXPRESSION; MATURATION; MODULATION AB The recognition and presentation of tumor-associated antigens by cutaneous antigen-presenting cells (APC) may play an important role in the establishment of effective defense mechanisms against newly emerging tumors in the skin. Recent data demonstrate the ability of I-A+ epidermal cells (Langerhans cells) to present tumor-associated antigens for the induction of protective tumor immunity and elicitation of delayed-type hypersensitivity against the murine spindle cell tumor, S1509a. Furthermore, the local cytokine microenvironment in the vicinity of a cutaneous neoplasm may regulate the ability of resident epidermal APC to initiate and/or to elicit protective immunity against incipient cutaneous neoplasms. This article summarizes the effects of granulocyte-macrophage/colony-stimulating factor (GM-CSF), interleukin-1alpha(IL-1alpha), tumor necrosis factor-alpha(TNFalpha), transforming growth factor-beta (TGFbeta), and interferon-gamma (IFNgamma) on the modulation of antigen presentation by epidermal APC. Our data indicate that these cytokines significantly and differentially modify the ability of epidermal cells to present tumor-associated antigens and that their effects differ with regard to induction of primary immunity (sensitization) or elicitation of secondary immune responses. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. FU NEI NIH HHS [EY07782]; NIAMS NIH HHS [AR40667] NR 28 TC 22 Z9 22 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1992 VL 99 IS 5 BP S66 EP S68 DI 10.1111/1523-1747.ep12669018 PG 3 WC Dermatology SC Dermatology GA JW928 UT WOS:A1992JW92800052 PM 1431232 ER PT J AU LANGHOFF, E HASELTINE, WA AF LANGHOFF, E HASELTINE, WA TI INFECTION OF ACCESSORY DENDRITIC CELLS BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL WORKSHOP ON LANGERHANS CELLS CY DEC 05-06, 1991 CL DALLAS, TX ID EPIDERMAL LANGERHANS CELLS; GENITAL MUCOSAL TRANSMISSION; AIDS-RELATED LYMPHADENOPATHY; POLYMERASE CHAIN-REACTION; TRANS-ACTIVATOR GENE; HUMAN LYMPHOCYTES-T; HTLV-III; GERMINAL-CENTERS; HIV-1 INFECTION; LYMPH-NODES AB Many details of the pathogenesis of the human immunodeficiency virus type 1 remain to be elucidated. Details of how the virus gains entry via the mucosal surface upon sexual contact or during breast feeding remain obscure. The means by which the infection travels throughout the body as well as the nature of the major reservoirs of virus infection remains, for the most part, unknown. Recent studies raise the possibility that cells of the Langerhans/dendritic lineage play a central role in human immunodeficiency virus (HIV-1) infection and pathogenesis. It has been known for several years that veiled dendritic cells in the circulation as well as skin Langerhans are infected in people with prolonged HIV-1 infections. More recently it has been found that a large burden of viral DNA sequences is found, not only in the circulating T-cell population, but also in a population that is defined as a non-T, non-B, non-monocyte/macrophage population rich in T-helper dendritic cells. Detailed analysis of infection of primary blood-derived T-helper dendritic cells by HIV-1 shows that such cells are the most susceptible cells in the blood to infection by this virus. The cells also produce much more virus per cell than do purified populations of other blood mononuclear cells. Moreover, primary blood-derived T-helper dendritic cells are not killed by infection by HIV-1. These cells are susceptible to lymphotropic, monocyte tropic, and primary isolates of HIV-1. The sensitivity of primary blood-derived T-helper dendritic cells to infection by HIV-1 has been shown to be attributable to rapid uptake of virus particles as well as rapid synthesis of viral DNA. Subsequent steps of virus replication also occur more rapidly and more efficiently in populations of primary blood-derived T-helper dendritic cells than they do in purified preparations of blood-derived T cells and monocyte/macrophages. Studies with primates using the simian immunodeficiency virus (SIV) show that dendritic cells at the surface of sexual mucosa are rapidly infected upon exposure to high concentrations of the virus. SIV is also produced in abundance in Langerhans cells located at the surface of the sexual mucosa in animals infected for prolonged periods of time. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115. FU NCI NIH HHS [P30CA06516]; NIAID NIH HHS [AI28734, P30AI28691] NR 75 TC 17 Z9 17 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 1992 VL 99 IS 5 BP S89 EP S94 DI 10.1111/1523-1747.ep12669964 PG 6 WC Dermatology SC Dermatology GA JW928 UT WOS:A1992JW92800060 PM 1431241 ER PT J AU WYRICK, SD BOOTH, RG MYERS, AM KULA, NS BALDESSARINI, RJ AF WYRICK, SD BOOTH, RG MYERS, AM KULA, NS BALDESSARINI, RJ TI SYNTHESIS OF [N-C3H3]-RACEMIC-TRANS-1-PHENYL-3-DIMETHYLAMINO-6-CHLORO-7-HYDROXY-1,2,3 ,4-TETRA-HYDRONAPHTHALENE (PAT-6) SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE 1-PHENYL-3-AMINOTETRALINS; TRITIUM; SIGMA RECEPTOR; DOPAMINE; PAT-6 ID GUINEA-PIG BRAIN; SIGMA LIGANDS; BINDING; RAT; RECEPTOR AB The biological function of the sigma receptor in the central nervous system is not well understood at the present time. Once thought to be an opiate receptor, the sigma receptor has now been shown to have a neuromodulatory effect upon the synthesis of dopamine in the striatal nerve terminal. A nerve sigma agonist, racemic-trans-1-phenyl-3-dimethylamino-6-chloro-7-hydroxy-1,2,3,4-tetrahydronaphthalene, PAT-6, has demonstrated the greatest potency of any compound tested to date as a sigma agonist in stimulating the synthesis of dopamine in vitro and may be functioning at a novel sigma receptor subtype. The synthesis of tritiated PAT-6 at high specific activity is described herein. This labeled ligand was prepared for use in radioreceptor binding studies in order to identify the putative sigma receptor subtype responsible for mediation of the stimulatory effect on in vitro synthesis. C1 MASSACHUSETTES GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA 02178. HARVARD UNIV,SCH MED,BELMONT,MA 02178. RP WYRICK, SD (reprint author), UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,RADIOSYNTH LAB,CHAPEL HILL,NC 27599, USA. NR 11 TC 7 Z9 7 U1 0 U2 1 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 NOV PY 1992 VL 31 IS 11 BP 871 EP 874 DI 10.1002/jlcr.2580311106 PG 4 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA JV918 UT WOS:A1992JV91800005 ER PT J AU FURTH, EE SPRECHER, H FISHER, EA FLEISHMAN, HD LAPOSATA, M AF FURTH, EE SPRECHER, H FISHER, EA FLEISHMAN, HD LAPOSATA, M TI AN INVITRO MODEL FOR ESSENTIAL FATTY-ACID DEFICIENCY - HEPG2 CELLS PERMANENTLY MAINTAINED IN LIPID-FREE MEDIUM SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ESSENTIAL FATTY ACIDS; ARACHIDONATE; MEAD ACID ID TISSUE-CULTURE; ARACHIDONATE; SECRETION; AGONIST; LINE; RELEASE AB A stable essential fatty acid-deficient cell type, known as HepG2-EFD, was derived from the lipoprotein-producing human hepatoma cell line HepG2. These cells are particularly useful for quantitative studies involving essential fatty acids (n-6 and n-3 fatty acids) in secreted lipoproteins. Radiolabeled essential fatty acids can be delivered to these cells without altering the specific activity of the fatty acids, since the deficient cells contain no endogenous essential fatty acids. Using these cells, radioactivity data (dpm) from metabolic studies can be converted directly to mass, and masses as low as a few pmoles can be accurately measured. HepG2-EFD cell cultures were established by growing HepG2 cells in medium containing delipidated serum. After 10 days of growth in delipidated medium, HepG2 cells were completely depleted of all essential fatty acids. Compensatory increases in nonessential fatty acids (n-9 and n-7 fatty acids) including 20:3n-9 (the Mead acid), which is the hallmark fatty acid of essential fatty acid deficiency, were also observed in HepG2-EFD cells. Despite the lack of exogenous fatty acids in the medium and the lack of essential fatty acids in the cells, export of very low density lipoprotein (VLDL)-associated apolipoprotein B by HepG2-EFD was the same as observed for parent HepG2 cells. However, the activity of beta-oxidation of fatty acids in HepG2-EFD cells was much lower than in the parent cell line. The doubling time was the same for both cell types, but depletion of essential fatty acids resulted in a phenotypic change, whereby HepG2 cells proliferated in large clusters of cells, but HepG2-EFD cells proliferated as homogeneously dispersed cell monolayers. Thus, cultures of HepG2-EFD cells provide an in vitro model for essential fatty acid deficiency, and the model has fatty acid changes consistent with those found in vivo in essential fatty acid deficiency. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,CLIN LABS,ROOM 249,GRAY BLDG,FRUIT ST,BOSTON,MA 02114. HOSP UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. MED COLL PENN,DEPT PHYSIOL & BIOCHEM,PHILADELPHIA,PA 19129. HARVARD UNIV,SCH MED,BOSTON,MA 02115. OHIO STATE UNIV,DEPT MED BIOCHEM,COLUMBUS,OH 43210. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-20387, DK-37454, DK-43159] NR 20 TC 22 Z9 22 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 1992 VL 33 IS 11 BP 1719 EP 1726 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA JW924 UT WOS:A1992JW92400016 PM 1464755 ER PT J AU AMES, A LI, YY AF AMES, A LI, YY TI ENERGY-REQUIREMENTS OF GLUTAMATERGIC PATHWAYS IN RABBIT RETINA SO JOURNAL OF NEUROSCIENCE LA English DT Article ID METHYL-D-ASPARTATE; MAGNETIC-RESONANCE SPECTROSCOPY; AMINO-ACID RECEPTORS; BIPOLAR CELLS; GANGLION-CELLS; 2-AMINO-4-PHOSPHONOBUTYRIC ACID; HUNTINGTONS-DISEASE; GLUCOSE CONSUMPTION; NMDA RECEPTORS; RAT AB In vitro rabbit retina was used as an example of CNS tissue in experiments designed to measure the energy requirements associated with the activation of different types of glutamate receptors. Retinas were exposed to glutamate and to four analogs: kainate, 2-amino-4-phosphonobutyric acid (APB), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and 2-amino-5-phosphonovaleric acid (APV). The changes in O2 consumption and lactate production were determined using a recently developed experimental system that permitted simultaneous measurements of the rates at which O2 was removed from the medium and acid was added. The glutamatergic agents had relatively little effect on oxidative metabolism, but they caused large changes in glycolysis. Kainate increased retinal lactate production by 50%, whereas APB, CNQX, and APV reduced it by 23%, 19%, and 35%, respectively. Glutamate increased lactate production by 16% when administered after APB, but decreased it by 12% when administered after CNQX. The changes in energy metabolism coincided with changes in electrophysiological function. Since the energy metabolism of many retinal cells was presumably not much affected by the glutamatergic agents, the changes measured as a percent of total retinal glycolysis must have reflected considerably larger fractional changes in the cells most affected. From the response to inhibitors, it seems probable that even under resting conditions in darkness, activity in glutamatergic pathways is responsible for more than 50% of the glycolytically derived energy used by the cells involved. It also seems probable (particularly from the response to kainate) that under some circumstances the cells' energy metabolism and/or transport capability cannot meet the requirements imposed by glutamate-induced increases in function. This may account for some aspects of glutamate toxicity. RP AMES, A (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,467 WARREN BLDG,BOSTON,MA 02114, USA. FU NINDS NIH HHS [NS25753] NR 45 TC 42 Z9 46 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV PY 1992 VL 12 IS 11 BP 4234 EP 4242 PG 9 WC Neurosciences SC Neurosciences & Neurology GA JY188 UT WOS:A1992JY18800009 PM 1359032 ER PT J AU CHEN, HSV PELLEGRINI, JW AGGARWAL, SK LEI, SZ WARACH, S JENSEN, FE LIPTON, SA AF CHEN, HSV PELLEGRINI, JW AGGARWAL, SK LEI, SZ WARACH, S JENSEN, FE LIPTON, SA TI OPEN-CHANNEL BLOCK OF N-METHYL-D-ASPARTATE (NMDA) RESPONSES BY MEMANTINE - THERAPEUTIC ADVANTAGE AGAINST NMDA RECEPTOR-MEDIATED NEUROTOXICITY SO JOURNAL OF NEUROSCIENCE LA English DT Article ID RETINAL GANGLION-CELLS; AMINO-ACID RECEPTORS; ANTICONVULSANT MK-801; GLUTAMATE TOXICITY; COAT PROTEIN; RAT; ANTAGONISTS; NEURONS; INVITRO; ACETYLCHOLINE AB Excessive activation of NMDA receptors is thought to mediate the calcium-dependent neurotoxicity associated with hypoxic-ischemic brain injury, trauma, epilepsy, and several neurodegenerative diseases. For this reason, various NMDA antagonists have been investigated for their therapeutic potential in these diseases, but heretofore none have proven to be both effective and safe. In the present study, memantine, an adamantane derivative similar to the antiviral drug amantadine, is shown to block the channels activated by NMDA receptor stimulation. From whole-cell and single-channel recording experiments, the mechanism of action of memantine is deduced to be open-channel block, similar to MK-801; however, unlike MK-801, memantine is well tolerated clinically. Compared to MK-801, memantine's safety may be related to its faster kinetics of action with rapid blocking and unblocking rates at low micromolar concentrations. Furthermore, at these levels memantine is an uncompetitive antagonist and should theoretically allow near-normal physiological NMDA activity throughout the brain even in the face of pathologically high focal concentrations of glutamate. These pharmacological properties confer upon memantine a therapeutic advantage against NMDA receptor-mediated neurotoxicity with few side effects compared with other organic NMDA open-channel blockers. Moreover, memantine is increasingly effective against escalating levels of glutamate, such as those observed during a stroke. Low micromolar concentrations of memantine, levels known to be tolerated by patients receiving the drug for the treatment of Parkinson's disease, prevent NMDA receptor-mediated neurotoxicity in cultures of rat cortical and retinal ganglion cell neurons; memantine also appears to be both safe and effective in a rat stroke model. These results suggest that memantine has considerable therapeutic potential for the myriad of clinical entities associated with NMDA receptor-mediated neurotoxicity. C1 CHILDRENS HOSP MED CTR,DEPT NEUROL,CELLULAR & MOLEC NEUROSCI LAB,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT NEUROL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT NEUROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. FU NEI NIH HHS [EY05477, EY09024]; NINDS NIH HHS [NS07264] NR 46 TC 446 Z9 458 U1 1 U2 11 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 NOV PY 1992 VL 12 IS 11 BP 4427 EP 4436 PG 10 WC Neurosciences SC Neurosciences & Neurology GA JY188 UT WOS:A1992JY18800024 PM 1432103 ER PT J AU TAKAMIYA, Y SHORT, MP EZZEDDINE, ZD MOOLTEN, FL BREAKEFIELD, XO MARTUZA, RL AF TAKAMIYA, Y SHORT, MP EZZEDDINE, ZD MOOLTEN, FL BREAKEFIELD, XO MARTUZA, RL TI GENE-THERAPY OF MALIGNANT BRAIN-TUMORS - A RAT GLIOMA LINE BEARING THE HERPES-SIMPLEX VIRUS TYPE-1-THYMIDINE KINASE GENE AND WILD-TYPE RETROVIRUS KILLS OTHER TUMOR-CELLS SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Note DE GENE TRANSFER; VIRAL VECTORS; TUMOR THERAPY; C6; HSV; TK; GANCICLOVIR ID TRANSGENIC MICE; NERVOUS-SYSTEM; CANCER; BROMODEOXYURIDINE; ASTROCYTOMAS; REPLICATION; INFECTION; PATTERNS; NEURONS; VECTORS AB Tumor cells infected with a retrovirus vector (VIK) containing the herpes simplex virus thymidine kinase (HSV-TK) gene can be selectively killed by treatment with nucleoside analogues, such as ganciclovir. To mediate delivery of the HSV-TK gene to "recipient" tumor cells, "donor" C6 rat glioma cells infected with the VIK vector (C6VIK) were superinfected with wild type Moloney murine leukemia virus (WT Mo-MLV). These modified donor cells (C6VIKWT) produced both wild type retrovirus and the VIK vector. In culture, C6VIKWT cells were 300-fold more sensitive to the toxicity of ganciclovir than were C6VIK cells, suggesting that the presence of wild type retrovirus contributed to the toxicity. Co-culture of C6VIKWT cells with the C6 subline, C6BAG, sensitized the latter to ganciclovir treatment. Nude mice inoculated subcutaneously with a mixture of C6VIKWT and C6BAG cells showed regression of subsequent tumors when treated with ganciclovir. The observations show that tumor cells modified in culture by infection with a retrovirus bearing the HSV-TK gene and wild type retrovirus are not only sensitive to ganciclovir, but can transfer this sensitivity to neighboring "naive" tumor cells in culture and in vivo. C1 MASSACHUSETTS GEN HOSP, NEUROL SERV, BLDG 149, ROOM 6203, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CTR NEUROSCI, NEUROSURG SERV, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, CTR NEUROSCI, NEUROL SERV, BOSTON, MA USA. HARVARD UNIV, SCH MED, NEUROSCI PROGRAM, BOSTON, MA 02115 USA. EDITH NOURSE ROGERS MEM VET ADM HOSP, BEDFORD, MA 01730 USA. BOSTON UNIV, BOSTON, MA 02215 USA. FU NINDS NIH HHS [NS24279]; PHS HHS [K08012151] NR 42 TC 175 Z9 176 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV PY 1992 VL 33 IS 3 BP 493 EP 503 DI 10.1002/jnr.490330316 PG 11 WC Neurosciences SC Neurosciences & Neurology GA JW086 UT WOS:A1992JW08600015 PM 1335091 ER PT J AU OHTANI, H CALLAHAN, RJ KHAW, BA FISHMAN, AJ WILKINSON, RA STRAUSS, HW AF OHTANI, H CALLAHAN, RJ KHAW, BA FISHMAN, AJ WILKINSON, RA STRAUSS, HW TI COMPARISON OF TECHNETIUM-99M-GLUCARATE AND TL-201 FOR THE IDENTIFICATION OF ACUTE MYOCARDIAL-INFARCTION IN RATS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID LOCALIZATION; INJURY AB The scintigraphic identification of acute severe ischemic myocardial injury requires a marker that localizes rapidly and specifically in zones of damaged myocardium. Technetium-99m-glucarate, a six-carbon dicarboxylic acid, which behaves in vivo somewhat like fructose, was recently described as a marker of severe acute ischemic injury with necrosis. This study was performed to determine the interval between the onset of myocardial ischemia and initial uptake and the duration of a positive scan in experimental animals. Serial injections and images were recorded over 10 days following ligation of the left anterior descending coronary artery of the rat. The distribution of Tc-99m-glucarate was compared to that of regional myocardial perfusion monitored with Tl-201. The findings on radionuclide imaging were compared to histologic changes in the myocardium. Sequential pinhole images of both radionuclides were collected at 3 hr, 24 hr, 72 hr and 7-10 days following ligation. Ten rats had normal Tl-201 distributions, no uptake of glucarate and no evidence of infarction by TTC staining at autopsy. Twenty-one rats had either Tl-201 lesions or evidence of infarction at autopsy. In 17 of these rats, significant acute Tc-99m-glucarate uptake was noted, decreasing at 24 hr, and was not seen at 72 hr or 7-10 days. The extent of perfusion abnormality was greatest at 3 hr in most animals; the lesion decreased in four (33%), increased in one (8%) and remained stable in the remainder. These data suggest that Tc-99m-glucarate may be a useful marker of acute myocardial injury. C1 MASSACHUSETTS GEN HOSP,DIV NUCL MED,FRUIT ST,BOSTON,MA 02114. NR 20 TC 21 Z9 21 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 NOV PY 1992 VL 33 IS 11 BP 1988 EP 1993 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JW929 UT WOS:A1992JW92900020 PM 1432160 ER PT J AU KIM, MR DONOFF, RB AF KIM, MR DONOFF, RB TI CRITICAL ANALYSIS OF MANDIBULAR RECONSTRUCTION USING AO RECONSTRUCTION PLATES SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID BONE-GRAFTS; DEFECTS; IMMEDIATE; FIXATION C1 MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02114. EWHA WOMANS UNIV,COLL MED,DEPT ORAL SURG,SEOUL,SOUTH KOREA. HARVARD UNIV,SCH DENT MED,BOSTON,MA 02115. NR 26 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 1992 VL 50 IS 11 BP 1152 EP 1157 DI 10.1016/0278-2391(92)90145-P PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA JW878 UT WOS:A1992JW87800002 PM 1403269 ER PT J AU BARR, SJ ZALESKE, DJ AF BARR, SJ ZALESKE, DJ TI PHYSEAL RECONSTRUCTION WITH BLOCKS OF CARTILAGE OF VARYING DEVELOPMENTAL TIME SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE BLOCKS OF CARTILAGE; DEVELOPMENT; PHYSIS; RECONSTRUCTION AB Reconstruction of physeal regions excised from the distal femoral chondroepiphysis was performed. in a murine model. The excised regions were replaced with analogous blocks of syngeneic tissue. Vascularity, matrix formation, and cell division were assessed as well as growth. The blocks of tissue did not produce growth consistently, although individual specimens did show some growth. Tritiated thymidine incorporation by the proliferative zone of the transplanted block of tissue was. not normal. The blocks of tissue did receive a nutritional supply from the host and did continue-matrix formation after transplantation. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED,ACC 507,BOSTON,MA 02114. FU NIAMS NIH HHS [AR39380] NR 0 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD NOV-DEC PY 1992 VL 12 IS 6 BP 766 EP 773 PG 8 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA JT994 UT WOS:A1992JT99400013 PM 1452748 ER PT J AU MURPHY, JM REEDE, J JELLINEK, MS BISHOP, SJ AF MURPHY, JM REEDE, J JELLINEK, MS BISHOP, SJ TI SCREENING FOR PSYCHOSOCIAL DYSFUNCTION IN INNER-CITY CHILDREN - FURTHER VALIDATION OF THE PEDIATRIC SYMPTOM CHECKLIST SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE PSYCHOSOCIAL SCREENING; PEDIATRIC SYMPTOM CHECKLIST; POVERTY AND CHILDREN ID MENTAL-HEALTH SERVICES; PRIMARY CARE; PREVALENCE; DISORDERS; PARENT; SCHOOL AB A sample of 123 6- to 12-year-old outpatients at an inner-city pediatric clinic was screened for psychosocial dysfunction using the Pediatric Symptom Checklist (PSC). a brief parent-completed questionnaire. The prevalence of positive screening scores on the PSC was 22%, significantly higher than the rate found in lower middle to upper middle-class samples. Comparing PSC case classifications with comprehensive assessments made by clinicians, overall agreement was 92% (kappa = 0.82; sensitivity = 88%; specificity = 100%); a comparison with several other measures provided additional support for the validity the PSC. The PSC's reliability over time was also acceptable. These findings provide preliminary evidence that the PSC is as valid and reliable for screening children from economically disadvantaged and minority backgrounds as it is for middle and upper middle-class populations. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. YALE UNIV,NEW HAVEN,CT 06520. RP MURPHY, JM (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,ACC 725,BOSTON,MA 02114, USA. FU PHS HHS [86MO4390351D] NR 29 TC 58 Z9 60 U1 3 U2 5 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 NOV PY 1992 VL 31 IS 6 BP 1105 EP 1111 DI 10.1097/00004583-199211000-00019 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA JX700 UT WOS:A1992JX70000019 PM 1429413 ER PT J AU SPENCER, TJ BIEDERMAN, J AF SPENCER, TJ BIEDERMAN, J TI GROWTH DEFICITS AND DESIPRAMINE - REPLY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter RP SPENCER, TJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 2 U2 2 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 NOV PY 1992 VL 31 IS 6 BP 1168 EP 1168 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA JX700 UT WOS:A1992JX70000032 ER PT J AU HERZOG, DB KELLER, MB LAVORI, PW GRAY, HM AF HERZOG, DB KELLER, MB LAVORI, PW GRAY, HM TI A BULIMIA FAMILY SURVEY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter ID WOMEN; ABUSE C1 BROWN UNIV,PROVIDENCE,RI 02912. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP HERZOG, DB (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA 02115, USA. NR 5 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 NOV PY 1992 VL 31 IS 6 BP 1170 EP 1171 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA JX700 UT WOS:A1992JX70000036 PM 1429428 ER PT J AU REIMOLD, SC THOMAS, JD LEE, RT AF REIMOLD, SC THOMAS, JD LEE, RT TI RELATION BETWEEN DOPPLER COLOR FLOW VARIABLES AND INVASIVELY DETERMINED JET VARIABLES IN PATIENTS WITH AORTIC REGURGITATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MITRAL REGURGITATION; INVITRO; ECHOCARDIOGRAPHY; INSUFFICIENCY; QUANTIFICATION; QUANTITATION; CATHETER; AREA AB Objectives. The purpose of this study was to test the hypothesis that invasively derived jet variables including regurgitant orifice area and momentum determine the characteristics of Doppler color flow jets in patients with aortic regurgitation. Background. In vitro studies have demonstrated that the velocity distribution of a regurgitant jet is best characterized by the momentum of the jet, which incorporates orifice area and velocity of flow through the orifice. Methods. Peak jet momentum, peak flow rate and regurgitant orifice area were determined with intraaortic Doppler catheter and cardiac catheterization techniques in 22 patients with chronic aortic regurgitation. These invasively derived variables were compared with apical and parasternal long-axis Doppler color echocardiographic variables obtained in the catheterization laboratory. Results. Jet momentum increased significantly with the angiographic grade of regurgitation. The apical color jet area of aortic regurgitation increased linearly with jet momentum and regurgitant orifice area in vivo, but the correlations were only moderately good (r = 0.63 and 0.65, respectively). Color jet length also increased linearly with jet momentum and with regurgitant orifice area. There was only a trend for Doppler color jet width to increase with all invasively derived jet variables. Conclusions. Whereas jet area by Doppler color flow imaging is directly related to both orifice area and jet momentum in vivo, Doppler color variables measured in planes normal to the orifice do not correlate well enough with either jet momentum or regurgitant orifice area to predict jet flow variables in patients with aortic regurgitation. It is likely that the important influence of adjacent boundaries will limit the use of the velocity distribution of aortic regurgitant jets for determining the severity of disease. C1 BRIGHAM & WOMENS HOSP,DEPT MED,DIV CARDIOVASC,NONINVAS CARDIAC LAB,75 FRANCIS ST,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-01835] NR 24 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 1 PY 1992 VL 20 IS 5 BP 1143 EP 1148 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW465 UT WOS:A1992JW46500015 PM 1401614 ER PT J AU HUTTER, AM AF HUTTER, AM TI STRIVING FOR EFFECTIVE COMMUNICATION SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material RP HUTTER, AM (reprint author), MASSACHUSETTS GEN HOSP,SUITE 467,15 PARKMAN ST,BOSTON,MA 02114, USA. 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 NOV 1 PY 1992 VL 20 IS 5 BP 1296 EP 1297 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA JW465 UT WOS:A1992JW46500036 PM 1401635 ER PT J AU SAINI, S AF SAINI, S TI PERCUTANEOUS ENDOSCOPIC GASTROSTOMIES SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Letter RP SAINI, S (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV GASTROINTESTINAL RADIOL,BOSTON,MA 02114, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC MEDICINE SERVICES LTD PI LONDON PA 1 WIMPOLE STREET, LONDON, ENGLAND W1M 8AE SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD NOV PY 1992 VL 85 IS 11 BP 714 EP 714 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA JW628 UT WOS:A1992JW62800029 PM 1474571 ER PT J AU PROUT, GR BARTON, BA GRIFFIN, PP FRIEDELL, GH AF PROUT, GR BARTON, BA GRIFFIN, PP FRIEDELL, GH TI TREATED HISTORY OF NONINVASIVE GRADE-1 TRANSITIONAL CELL-CARCINOMA SO JOURNAL OF UROLOGY LA English DT Article DE CARCINOMA; TRANSITIONAL CELL; BLADDER NEOPLASMS ID FLUORESCENCE IMAGE-ANALYSIS; SUPERFICIAL BLADDER-CANCER; FLOW-CYTOMETRY; URINARY-BLADDER; PAPILLARY CARCINOMA; NATURAL-HISTORY; FOLLOW-UP; RECURRENCE; CYTOLOGY; TUMORS AB A total of 178 patients with grade 1 noninvasive (stage Ta) bladder tumors followed from 1 to 10 years (median 58 months) was prospectively evaluated by cystoscopy, transurethral resection, mucosal biopsies, cytology, size and number of tumors at diagnosis, recurrences, progression in grade and stage, number of negative or positive cystoscopies and death from all causes. Histopathological and cytological studies were confirmed by a Central Pathology Laboratory using the criteria for grade 1 as described previously. Of the patients 122 (68.5%) had a single tumor. Three-quarters of the patients had tumors of less than 2 cm., 95% had mild or no urothelial dysplasia and 1 had positive cytology results. There were 419 recurrent tumors in 109 patients (61%). Patients with multiple tumors were at a significantly greater risk for recurrences (p <0.001). Size of tumor significantly affected the rate of recurrence in the first 2 years after initial diagnosis in single tumor patients only. Of the multiple tumor patients 90% experienced a recurrence compared to 46% of the single tumor patients. Of the 1,112 cystoscopies performed in 122 single tumor patients 18% were positive, compared to 33% of the 686 cystoscopies performed in 56 multiple tumor patients. A total of 29 patients had a change in grade, 5 having grade 3 and 24 having grade 2 tumors. Progression to stage T1 occurred in 5 patients and to stage T2 or greater in 3. Of the 36 patients who died, 1 died of obstruction due to bladder cancer. Experimental evidence supports the opinion that the cells of stage Ta, grade 1 tumors are different in several ways from normal urothelium. There are little data to support the use of the term papilloma to describe stage Ta, grade 1 tumors without reservation. The data demonstrate that the tumor diathesis being expressed ceases with time and for unknown reasons. Multiple tumor patients with stage Ta, grade 1 disease might be included in chemotherapy trials only with stratification and a control arm of transurethral resection/fulguration alone. C1 MARYLAND MED RES INST,BALTIMORE,MD. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. VIRGINIA MASON RES CTR,SEATTLE,WA 98101. WALTER REED ARMY MED CTR,BETHESDA,MD. UNIV IOWA,IOWA CITY,IA 52242. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. UNIV OREGON,PORTLAND,OR. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,BUFFALO,NY 14263. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. UNIV WISCONSIN,MADISON,WI 53706. UNIV FLORIDA,GAINESVILLE,FL 32611. UNIV KENTUCKY,LOUISVILLE,KY. CLEVELAND CLIN,CLEVELAND,OH 44106. UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. FU NCI NIH HHS [CA15934, CA17466, CA23082] NR 49 TC 119 Z9 122 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1992 VL 148 IS 5 BP 1413 EP 1419 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA JW460 UT WOS:A1992JW46000009 PM 1433540 ER PT J AU OLEARY, MP BARRY, MJ FOWLER, FJ AF OLEARY, MP BARRY, MJ FOWLER, FJ TI HARD MEASURES OF SUBJECTIVE OUTCOMES - VALIDATING SYMPTOM INDEXES IN UROLOGY SO JOURNAL OF UROLOGY LA English DT Note DE UROLOGIC DISEASES; PROSTATIC HYPERTROPHY; PATIENT CARE PLANNING; DIAGNOSIS ID PERFORMANCE AB Scientifically validated (accurate), and reproducible (precise) methods of assessing the frequency and severity of patient symptoms are becoming more widely used in medicine. Such a symptom index has been developed for patients with benign prostatic hyperplasia, and may find use in clinical practice and research. The criteria for developing and validating such indexes are presented, using the new benign prostatic hyperplasia symptom index as an example. The same approach can be applied to many other disease entities in urology that demand a quantitation of the illness experience from the perspective of the patients. C1 MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,CTR SURVEY RES,AMHERST,MA 01003. RP OLEARY, MP (reprint author), TUFTS UNIV,SCH MED,DEPT UROL,BOSTON,MA 02111, USA. NR 13 TC 63 Z9 65 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1992 VL 148 IS 5 BP 1546 EP 1548 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA JW460 UT WOS:A1992JW46000057 PM 1279217 ER PT J AU BARRY, MJ FOWLER, FJ OLEARY, MP BRUSKEWITZ, RC HOLTGREWE, HL MEBUST, WK COCKETT, ATK BLAIVAS, JG WEIN, AJ AF BARRY, MJ FOWLER, FJ OLEARY, MP BRUSKEWITZ, RC HOLTGREWE, HL MEBUST, WK COCKETT, ATK BLAIVAS, JG WEIN, AJ TI THE AMERICAN-UROLOGICAL-ASSOCIATION SYMPTOM INDEX FOR BENIGN PROSTATIC HYPERPLASIA SO JOURNAL OF UROLOGY LA English DT Note DE PROSTATIC HYPERTROPHY; PROSTATIC DISEASES; STATISTICS ID PROSTATECTOMY AB A symptom index for benign prostatic hyperplasia (BPH) was developed and validated by a multidisciplinary measurement committee of the American Urological Association (AUA). Validation studies were conducted involving a total of 210 BPH patients and 108 control subjects. The final AUA symptom index includes 7 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency. On revalidation, the index was internally consistent (Cronbach's alpha = 0.86) and the score generated had excellent test-retest reliability (r = 0.92). Scores were highly correlated with subjects' global ratings of the magnitude of their urinary problem (r = 0.65 to 0.72) and powerfully discriminated between BPH and control subjects (receiver operating characteristic area 0.85). Finally, the index was sensitive to change, with preoperative scores decreasing from a mean of 17.6 to 7.1 by 4 weeks after prostatectomy (p < 0.001). The AUA symptom index is clinically sensible, reliable, valid and responsive. It is practical for use in practice and for inclusion in research protocols. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,CTR SURVEY RES,AMHERST,MA 01003. TUFTS UNIV,SCH MED,DEPT UROL,BOSTON,MA 02111. UNIV WISCONSIN,DEPT UROL,MADISON,WI 53706. JOHNS HOPKINS UNIV,DEPT UROL,BALTIMORE,MD 21218. UNIV ROCHESTER,MED CTR,DEPT UROL,ROCHESTER,NY 14642. UNIV KANSAS,MED CTR,UROL SECT,KANSAS CITY,KS 66103. COLUMBIA UNIV COLL PHYS & SURG,DEPT UROL,NEW YORK,NY 10032. UNIV PENN,SCH MED,DIV UROL,PHILADELPHIA,PA 19104. RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114, USA. NR 17 TC 1914 Z9 1953 U1 1 U2 17 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1992 VL 148 IS 5 BP 1549 EP 1557 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA JW460 UT WOS:A1992JW46000058 PM 1279218 ER PT J AU BARRY, MJ FOWLER, FJ OLEARY, MP BRUSKEWITZ, RC HOLTGREWE, HL MEBUST, WK BLAIVAS, JG COCKETT, ATK WEIN, AJ AF BARRY, MJ FOWLER, FJ OLEARY, MP BRUSKEWITZ, RC HOLTGREWE, HL MEBUST, WK BLAIVAS, JG COCKETT, ATK WEIN, AJ TI CORRELATION OF THE AMERICAN-UROLOGICAL-ASSOCIATION SYMPTOM INDEX WITH SELF-ADMINISTERED VERSIONS OF THE MADSEN-IVERSEN, BOYARSKY AND MAINE MEDICAL ASSESSMENT PROGRAM SYMPTOM INDEXES SO JOURNAL OF UROLOGY LA English DT Note DE PROSTATIC HYPERTROPHY; PROSTATIC DISEASES; STATISTICS ID RESECTION; PROSTATE AB We correlated the American Urological Association (AUA) symptom index with other indexes that have been used to measure symptoms for benign prostatic hyperplasia (BPH) and compared their psychometric properties. A self-administered questionnaire that allowed derivation of AUA, Maine Medical Assessment Program, Madsen-Iversen and Boyarsky symptom scores was completed by 76 men with clinically defined BPH, 59 younger control subjects, and 27 men before and after prostatectomy. The scores from the 4 indexes were strongly correlated (r = 0.77 to 0.93). All 4 indexes had good internal consistency and test-retest reliabilities. All indexes were predictive of patient global ratings of the degree of bother from the urinary condition. The AUA index discriminated BPH patients from controls significantly better than the Maine Medical Assessment Program index, and equivalently to the Madsen-Iversen and Boyarsky indexes (despite having fewer items). All 4 indexes were responsive when BPH patients underwent prostatectomy, although the AUA and Madsen-Iversen indexes were significantly more sensitive. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV MASSACHUSETTS,CTR SURVEY RES,AMHERST,MA 01003. TUFTS UNIV,SCH MED,DEPT UROL,BOSTON,MA 02111. UNIV WISCONSIN,DEPT UROL,MADISON,WI 53706. JOHNS HOPKINS UNIV,DEPT UROL,BALTIMORE,MD 21218. UNIV KANSAS,MED CTR,DIV UROL,KANSAS CITY,KS 66103. COLUMBIA UNIV COLL PHYS & SURG,DEPT UROL,NEW YORK,NY 10032. UNIV ROCHESTER,MED CTR,DEPT UROL,ROCHESTER,NY 14642. UNIV PENN,SCH MED,DIV UROL,PHILADELPHIA,PA 19104. RP BARRY, MJ (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114, USA. NR 11 TC 159 Z9 160 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 1992 VL 148 IS 5 BP 1558 EP 1563 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA JW460 UT WOS:A1992JW46000059 PM 1279219 ER PT J AU GABUZDA, DH LAWRENCE, K LANGHOFF, E TERWILLIGER, E DORFMAN, T HASELTINE, WA SODROSKI, J AF GABUZDA, DH LAWRENCE, K LANGHOFF, E TERWILLIGER, E DORFMAN, T HASELTINE, WA SODROSKI, J TI ROLE OF VIF IN REPLICATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN CD4+ T LYMPHOCYTES SO JOURNAL OF VIROLOGY LA English DT Article ID SOR GENE-PRODUCT; NUCLEOTIDE-SEQUENCE; HTLV-III/LAV; CYTOPATHIC RETROVIRUSES; AIDS VIRUS; EXPRESSION; HIV-1; INFECTION; MOLECULES; PROTEIN AB The viral infectivity factor gene vif of human immunodeficiency virus type 1 has been shown to affect the infectivity but not the production of virus particles. In this study, the effect of vif in the cont"t of the HXB2 virus on virus replication in several CD4+ T-cell lines was investigated. vif was found to be required for replication in the CD4+ T-cell lines CEM and H9 as well as in peripheral blood T lymphocytes. vif was not required for replication in the SupT1, C8166, and Jurkat T-cell lines. The infectivity of vif-defective viruses depended on the cell type in which the virus was produced. In CEM cells, vif was required for production of virus capable of initiating infection in all cell lines studied. vif-defective virus produced by SupT1, C8166, and Jurkat cells and the monkey cell line COS-1 could initiate infection in multiple cell lines, including CEM and H9. These results suggest that vif can compensate for cellular factors required for production of infectious virus particles that are present in some cell lines such as SupT1, C8166, and Jurkat but are absent in others such as CEM and H9 as well as peripheral blood T lymphocytes. The effect of vif was not altered by deletion of the carboxyl terminus of gp41, a proposed target for vif (B. Guy, M. Geist, K. Dott, D. Spehner, M.-P. Kieny, and J.-P. Lecocq, J. Virol. 65:1325-1331, 1991). These studies demonstrate that vif enhances viral infectivity during virus production and also suggest that vif is likely to be important for natural infections. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI01017, AI24755, AI31354] NR 33 TC 358 Z9 367 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1992 VL 66 IS 11 BP 6489 EP 6495 PG 7 WC Virology SC Virology GA JT700 UT WOS:A1992JT70000027 PM 1357189 ER PT J AU KOPANS, DB AF KOPANS, DB TI SCREENING MAMMOGRAPHY IN WOMEN OVER AGE 65 SO JOURNALS OF GERONTOLOGY LA English DT Article ID DETECTION DEMONSTRATION PROJECT; BREAST-CANCER; TUMOR SIZE; MORTALITY; SURVIVAL; TRIAL; CARCINOMA; REDUCTION AB Routine screening by mammography and physical examination can detect breast cancers earlier at all ages. In women over ap 65 the sensitivity of mammography is increased, and the positive predictive value for mammography is higher than in younger women. There are no direct data that can be used to determine at what age screening is no longer of value. This question must be evaluated on an individual basis and should take into account the quality of life and competing causes of death. The medical benefit from screening for a given individual should be considered separately from society's cost/benefit goal to reduce health care expenditures, because the two are likely to produce contradictory recommendations. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 30 TC 20 Z9 20 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1992 VL 47 SI SI BP 59 EP 62 PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA KA426 UT WOS:A1992KA42600010 PM 1430884 ER PT J AU MASORO, EJ MCCARTER, RJM KATZ, MS MCMAHAN, CA AF MASORO, EJ MCCARTER, RJM KATZ, MS MCMAHAN, CA TI DIETARY RESTRICTION ALTERS CHARACTERISTICS OF GLUCOSE FUEL USE SO JOURNALS OF GERONTOLOGY LA English DT Article ID FED AD-LIBITUM; FOOD RESTRICTION; CALORIC RESTRICTION; INSULIN ACTION; METABOLIC-RATE; AGE; LONGEVITY; EXERCISE; DISEASE; MASS AB A longitudinal study of plasma glucose and insulin concentrations in ad libitum fed and dietary restricted male F344 rats was carried out. The life span diurnal pattern of plasma glucose concentration was such that through most of the day dietary restricted rats have significantly lower plasma glucose levels than ad libitum fed rats. Throughout the life span, dietary restricted rals maintain mean 24-hour plasma glucose concentrations about 15% below those of ad libitum fed rats. Plasma insulin levels are maintained in dietary restricted rats at about 50% of the levels in ad libitum fed rats. Although plasma glucose and insulin levels are lower, dietary restricted rats use glucose fuel at the same rate per unit of metabolic mass per day as rats fed ad libitum. While these findings are consistent with the glycation hypothesis of aging and with our hypothesis that dietary restriction retards the aging processes by altering the characteristics of fuel use, they do not establish the validity of either. It is possible that this effect of dietary restriction on carbohydrate metabolism plays no role in its antiaging action. Further studies are required to define the role of these altered characteristics of carbohydrate metabolism in the aging processes. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC CLIN,SAN ANTONIO,TX 78284. RP MASORO, EJ (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [AG-01188] NR 29 TC 184 Z9 188 U1 0 U2 7 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD NOV PY 1992 VL 47 IS 6 BP B202 EP B208 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA JX157 UT WOS:A1992JX15700018 PM 1430849 ER PT J AU BLOCH, KJ BUCHANAN, WW WOHL, MJ BUNIM, JJ AF BLOCH, KJ BUCHANAN, WW WOHL, MJ BUNIM, JJ TI SJOGRENS-SYNDROME - A CLINICAL, PATHOLOGICAL, AND SEROLOGICAL STUDY OF 62 CASES SO MEDICINE LA English DT Article C1 MASSACHUSETTS GEN HOSP,IMMUNOL UNIT,BOSTON,MA 02114. MCMASTER UNIV,HLTH SCI CTR,RHEUMAT DIS UNIT,HAMILTON L8S 4L8,ONTARIO,CANADA. HARVARD UNIV,MED AREA HLTH SERV,CAMBRIDGE,MA 02138. RP BLOCH, KJ (reprint author), MASSACHUSETTS GEN HOSP,CLIN IMMUNOL UNIT,BOSTON,MA 02114, USA. NR 0 TC 22 Z9 23 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 1992 VL 71 IS 6 BP 386 EP 401 DI 10.1097/00005792-199211000-00005 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA JZ414 UT WOS:A1992JZ41400005 PM 1435231 ER PT J AU TALAL, N AF TALAL, N TI SJOGRENS-SYNDROME - A PRESENT-DAY VIEW SO MEDICINE LA English DT Note C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. RP TALAL, N (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,CLIN IMMUNOL SECT,SAN ANTONIO,TX 78284, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 1992 VL 71 IS 6 BP 401 EP 403 DI 10.1097/00005792-199211000-00006 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA JZ414 UT WOS:A1992JZ41400006 ER PT J AU YOUNG, RH AF YOUNG, RH TI NEPHROGENIC ADENOMAS OF THE URETHRA INVOLVING THE PROSTATE-GLAND - A REPORT OF 2 CASES OF A LESION THAT MAY BE CONFUSED WITH PROSTATIC ADENOCARCINOMA SO MODERN PATHOLOGY LA English DT Article DE PROSTATE GLAND; NEPHROGENIC ADENOMA; URETHRA ID CLEAR CELL ADENOCARCINOMA; FEMALE URETHRA; METAPLASIA; BLADDER AB Two cases of urethral nephrogenic adenoma involving the prostate are described. A diagnosis of prostatic carcinoma was raised in both cases and was seriously entertained in one of them. The patients, who were 65 and 68 yr old, underwent transurethral resection because of difficulty voiding; both had had a prior similar procedure. Microscopic examination in each case showed small tubules and clusters of cells in the fibromuscular stroma of the prostate. In one case the lesional cells had abundant clear cytoplasm, and in both cases some of the nuclei had prominent nucleoli. In each case a minor component of the cystic pattern of nephrogenic adenoma was also present. Features pointing to a diagnosis of nephrogenic adenoma were a morphology that was focally characteristic of that lesion, an origin from overlying prostatic urethra in both cases, and negative immunohistochemical staining of the lesional cells for prostate-specific antigen and prostate-specific acid phosphatase. These cases illustrate that nephrogenic adenoma occasionally involves the prostate and in these cases can potentially be confused with prostatic adenocarcinoma. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP YOUNG, RH (reprint author), MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 19 TC 19 Z9 19 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD NOV PY 1992 VL 5 IS 6 BP 617 EP 620 PG 4 WC Pathology SC Pathology GA KF158 UT WOS:A1992KF15800009 PM 1369796 ER PT J AU PRASAD, KVS RUDD, CE AF PRASAD, KVS RUDD, CE TI A RAF-1-RELATED P110 POLYPEPTIDE ASSOCIATES WITH THE CD4-P56LCK COMPLEX IN T-CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; LYMPHOCYTES-T; CROSS-LINKING; CD4; ACTIVATION; PHOSPHORYLATION; P56LCK; RAF-1 AB The CD4 and CD8 antigens on T cells have been shown to associate with the Src family member p56lck and a GTP-binding protein, p32. The identification of receptor interactions with intracellular mediators is essential in the elucidation of downstream signals mediated by engagement of these receptor complexes. In this study, we report the detection of an additional 110-kDa polypeptide (p110) associated with the CD4-p56lck complex in human peripheral blood T lymphocytes and leukemic T-cell lines. p110 bound preferentially to CD4-p56lck as an assembled complex and poorly, if at all, to the individual components. p110 was recognized directly by an antiserum to the C-terminal region of the serine/threonine kinase Raf-1 and is related to a p110 polypeptide detected in anti-Raf-1 immunoprecipitates. Despite its association with the CD4-p56lck complex, p110 was found to be phosphorylated predominantly on serine residues. Furthermore, phorbal ester treatment of cells resulted in a transient increase in the detection of p110 associated with CD4-p56lck, concomitant with the modulation of CD4-p56lck from the cell surface. This Raf-1-related p110 is therefore likely to play a role in signals generated from the CD4-p56lck complex. p110 may serve as a bridge between the CD4-p56lck complex and the serine/threonine kinase pathways of T-cell activation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI2069016, AI125505-01] NR 61 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1992 VL 12 IS 11 BP 5260 EP 5267 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA JT845 UT WOS:A1992JT84500047 PM 1406695 ER PT J AU KAY, TWH JAMESON, JL AF KAY, TWH JAMESON, JL TI IDENTIFICATION OF A GONADOTROPIN-RELEASING HORMONE-RESPONSIVE REGION IN THE GLYCOPROTEIN HORMONE ALPHA-SUBUNIT PROMOTER SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; PROTEIN-BINDING DOMAINS; GENE-EXPRESSION; DIFFERENTIAL REGULATION; TRANSCRIPTION FACTORS; KINASE-C; PITUITARY; BETA; ELEMENT; FREQUENCY AB Transcriptional regulation of the glycoprotein hormone alpha-subunit gene has been studied extensively in placental cells, but much less is known about its regulation in the pituitary gland. In this study, transcriptional control of the human alpha-subunit gene by GnRH was analyzed using transient expression assays in primary cultures of rat pituitary cells using alpha promoter contructs linked to a luciferase reporter gene. Deletion mutants between -846 and -156 basepairs (bp) had little effect on basal expression, but further deletion to -132 bp reduced basal activity by approximately 50%. Deletion of a cAMP response element between -132 and -99 bp caused a marked loss of basal activity, reducing expression to that of background luciferase activity. The same constructs were analyzed for cAMP responsiveness in primary pituitary cells. The degree of stimulation with 1 mM 8-bromo-cAMP (3.6- to 6.0-fold) was relatively unaffected by deletions from -846 to -132 bp, whereas cAMP stimulation was decreased by further deletion to -99 bp, consistent with the presence of previously defined cAMP response elements in this region of the alpha promoter. GnRH stimulation of alpha promoter activity was highly dependent upon the time of hormone addition after transfection, being most effective when added soon after transfection. Under optimal conditions, GnRH stimulated -846alphaLUC expression by 20-fold. GnRH responsiveness was retained with deletion to -346 bp, but it was decreased by 55% after deletion to -280 bp and by 79% with deletion to -244 bp. A series of DNA sequences between -346 and -180 bp was linked to the truncated -132alpha promoter to define the GnRH-responsive region in more detail. Sequences between -346/-180 and -346/-244 conferred greater GnRH responsiveness than was seen with a -346/-280 fragment, confirming an important role for the region between -280 and -244 bp for GnRH responsiveness. These studies suggest that the transcriptional response to GnRH is mediated through one or more elements between -346 and -244 bp and that GnRH-responsive sequences are distinct from those involved in basal and cAMP-stimulated expression of the alpha promoter. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,THYROID UNIT,JACKSON 1021,BOSTON,MA 02114. OI Jameson, James/0000-0001-9538-4059 FU NICHD NIH HHS [HD-28138, HD-29164] NR 36 TC 72 Z9 72 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1992 VL 6 IS 11 BP 1767 EP 1773 DI 10.1210/me.6.11.1767 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB015 UT WOS:A1992KB01500001 PM 1282668 ER PT J AU LEE, JW GULICK, T MOORE, DD AF LEE, JW GULICK, T MOORE, DD TI THYROID-HORMONE RECEPTOR DIMERIZATION FUNCTION MAPS TO A CONSERVED SUBREGION OF THE LIGAND-BINDING DOMAIN SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN ESTROGEN-RECEPTOR; DNA-BINDING; GLUCOCORTICOID RECEPTOR; TRANSCRIPTIONAL ACTIVATION; STEROID BINDING; NUCLEAR-PROTEIN; T3 RECEPTOR; REGION; COLOCALIZATION; DETERMINES AB Thyroid hormone receptors (TRs) bind as dimers to specific DNA response elements. We have used a genetic approach to identify amino acid sequences required for dimerization of the TRbeta isoform. Bacteria expressing a chimeric repressor composed of the DNA binding domain of the bacteriophage lambda cl repressor fused to the TRbeta ligand binding domain are immune to lambda infection as a consequence of homodimerization activity provided by the receptor sequences. The phenotypes of deletions and point mutations of the TRbeta sequences map dimerization activity to a subregion of the ligand binding domain that is highly conserved among all members of the nuclear hormone receptor superfamily. These results confirm and extend previous findings indicating that this subregion plays an important role in the dimerization of TRbeta and other superfamily members. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. FU NIDDK NIH HHS [DK-43382] NR 53 TC 47 Z9 47 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1992 VL 6 IS 11 BP 1867 EP 1873 DI 10.1210/me.6.11.1867 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KB015 UT WOS:A1992KB01500013 PM 1480176 ER PT J AU TONNER, PH WOOD, SC MILLER, KW AF TONNER, PH WOOD, SC MILLER, KW TI CAN NICOTINE SELF-INHIBITION ACCOUNT FOR ITS LOW EFFICACY AT THE NICOTINIC ACETYLCHOLINE-RECEPTOR FROM TORPEDO SO MOLECULAR PHARMACOLOGY LA English DT Article ID ION CHANNELS; POSTSYNAPTIC MEMBRANES; BLOCK CURRENTS; AGONIST; ETHANOL; SITES AB Nicotine, a partial agonist, has a very low efficacy at the nicotinic acetylcholine receptor from Torpedo, but it is not clear whether this is because it is intrinsically poor at opening the ion channel or because, at concentrations that open the channel, it is also capable of blocking it. In this study, we exploited the action of ethanol, which increases the apparent affinity of cholinergic agonists for channel activation, and demonstrated that the weak action of nicotine is consistent with simultaneous activation and inhibition of the receptor. The presence of ethanol increased the efficacy of nicotine, producing an increase in the initial rate of cation efflux from acetylcholine receptor-rich membrane vesicles, as measured by a rapid quench-flow tracer ion assay. The initial rate of efflux increased with ethanol concentration until, in the presence of 1.5 M ethanol, the response to nicotine was indistinguishable from that of the full agonist carbamylcholine. The concentration-response curves for nicotine were bell-shaped, showing activation at low concentrations and inhibition at higher concentrations. increasing concentrations of ethanol increased the apparent affinity of nicotine for channel activation and decreased its apparent affinity for channel inhibition. These actions broadened the bell-shaped curve, increasing the maximum response until it was equivalent to that of a full agonist. The apparent affinity of nicotine for its inhibitory site, derived from the aforementioned data, agreed with that determined independently by measuring the inhibition by nicotine of initial rates of ion efflux in response to acetylcholine. A value for the apparent affinity of nicotine for channel opening was estimated from the dependence of this parameter on ethanol concentration. When combined, these two parameters predicted the bell-shaped concentration-response curve for the action of nicotine. The results presented in this study are consistent with the notion that the efficacy of nicotine is determined by its relative affinities for channel activation and channel inhibition, but they do not rule out other contributions. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. RP TONNER, PH (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02115, USA. FU NIAAA NIH HHS [AA-07040] NR 30 TC 17 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1992 VL 42 IS 5 BP 890 EP 897 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA JY342 UT WOS:A1992JY34200021 PM 1279379 ER PT J AU TAYLOR, SAM SNELL, RG BUCKLER, A AMBROSE, C DUYAO, M CHURCH, D LIN, CS ALTHERR, M BATES, GP GROOT, N BARNES, G SHAW, DJ LEHRACH, H WASMUTH, JJ HARPER, PS HOUSMAN, DE MACDONALD, ME GUSELLA, JF AF TAYLOR, SAM SNELL, RG BUCKLER, A AMBROSE, C DUYAO, M CHURCH, D LIN, CS ALTHERR, M BATES, GP GROOT, N BARNES, G SHAW, DJ LEHRACH, H WASMUTH, JJ HARPER, PS HOUSMAN, DE MACDONALD, ME GUSELLA, JF TI CLONING OF THE ALPHA-ADDUCIN GENE FROM THE HUNTINGTONS-DISEASE CANDIDATE REGION OF CHROMOSOME-4 BY EXON AMPLIFICATION SO NATURE GENETICS LA English DT Article ID PROTEIN KINASE-C; ERYTHROCYTE ADDUCIN; LINKAGE DISEQUILIBRIUM; PHOSPHORYLATION; MEMBRANE; SITES; IDENTIFICATION; ASSOCIATION; SUBSTRATE; RATS AB We have applied the technique of exon amplification to the isolation of genes from the chromosome 4p16.3 Huntington's disease (HD) candidate region. Exons recovered from cosmid Y24 identified cDNA clones corresponding to the alpha-subunit of adducin, a calmodulin-binding protein that is thought to promote assembly of spectrin-actin complexes in the formation of the membrane cytoskeleton. Alpha-adducin is widely expressed and, at least in brain, is encoded by alternatively spliced mRNAs. The alpha-adducin gene maps immediately telomeric to D4S95, in a region likely to contain the HD defect, and must be scrutinized to establish whether it is the site of the HD mutation. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. IMPERIAL CANC RES FUND,LONDON WC2A 3PX,ENGLAND. UNIV WALES COLL MED,INST MED GENET,CARDIFF CF4 4XN,S GLAM,WALES. MIT,CTR CANC RES,CAMBRIDGE,MA 02139. UNIV CALIF IRVINE,DEPT BIOL CHEM,IRVINE,CA 92717. RP TAYLOR, SAM (reprint author), MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02114, USA. RI Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 NR 35 TC 43 Z9 44 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1992 VL 2 IS 3 BP 223 EP 227 DI 10.1038/ng1192-223 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA JW165 UT WOS:A1992JW16500013 PM 1345173 ER PT J AU GLASER, T WALTON, DS MAAS, RL AF GLASER, T WALTON, DS MAAS, RL TI GENOMIC STRUCTURE, EVOLUTIONARY CONSERVATION AND ANIRIDIA MUTATIONS IN THE HUMAN PAX6 GENE SO NATURE GENETICS LA English DT Article ID BOX-CONTAINING GENE; WILMS TUMOR; NEURAL-TUBE; MOUSE; MAP; EXPRESSION; DELETION; LOCUS; 11P13; LENS AB Aniridia is a semidominant disorder in which development of the iris, lens, cornea and retina is disturbed. The mouse mutation Small eye (Sey), which has been proposed as a model for aniridia, results from defects in Pax-6, a gene containing paired-box and homeobox motifs that is specifically expressed in the developing eye and brain. To test the role of PAX6 in aniridia, we isolated human cDNA clones and determined the intron-exon structure of this gene. PAX6 spans 22 kilobases and is divided into 14 exons. Analysis of DNA from 10 unrelated aniridia patients revealed intragenic mutations in three familial and one sporadic case. These findings indicate that the human aniridia and murine Small eye phenotypes arise from homologous defects in PAX6. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV GENET, BOSTON, MA 02115 USA. HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, BOSTON, MA 02114 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. NR 62 TC 457 Z9 474 U1 4 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 1992 VL 2 IS 3 BP 232 EP 239 DI 10.1038/ng1192-232 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA JW165 UT WOS:A1992JW16500015 PM 1345175 ER PT J AU OLSSON, JE GORDON, JW PAWLYK, BS ROOF, D HAYES, A MOLDAY, RS MUKAI, S COWLEY, GS BERSON, EL DRYJA, TP AF OLSSON, JE GORDON, JW PAWLYK, BS ROOF, D HAYES, A MOLDAY, RS MUKAI, S COWLEY, GS BERSON, EL DRYJA, TP TI TRANSGENIC MICE WITH A RHODOPSIN MUTATION (PRO23HIS) - A MOUSE MODEL OF AUTOSOMAL DOMINANT RETINITIS-PIGMENTOSA SO NEURON LA English DT Article ID I HISTOCOMPATIBILITY MOLECULES; PANCREATIC BETA-CELLS; OCULAR FINDINGS; ONE FORM; GENE; EXPRESSION; HETEROGENEITY; DELETION; DEFECT; OPSIN AB We inserted into the germline of mice either a mutant or wild-type allele from a patient with retinitis pigmentosa and a missense mutation (P23H) in the rhodopsin gene. All three lines of transgenic mice with the mutant allele developed photoreceptor degeneration; the one with the least severe retinal photoreceptor degeneration had the lowest transgene expression, which was one-sixth the level of endogenous murine rod opsin. Of two lines of mice with the wild-type allele, one expressed approximately equal amounts of transgenic and murine opsin and maintained normal retinal function and structure. The other expressed approximately 5 times more transgenic than murine opsin and developed a retinal degeneration similar to that found in mice carrying a mutant allele, presumably due to the overexpression of this protein. Our findings help to establish the pathogenicity of mutant human P23H rod opsin and suggest that overexpression of wild-type human rod opsin leads to a remarkably similar photoreceptor degeneration. C1 UNIV BRITISH COLUMBIA,DEPT BIOCHEM,VANCOUVER V6T 1Z3,BC,CANADA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. CUNY MT SINAI SCH MED,DEPT OBSTET & GYNECOL,NEW YORK,NY 10029. RP OLSSON, JE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. FU NEI NIH HHS [EY06514, EY00169, EY 08683] NR 44 TC 331 Z9 336 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1992 VL 9 IS 5 BP 815 EP 830 DI 10.1016/0896-6273(92)90236-7 PG 16 WC Neurosciences SC Neurosciences & Neurology GA JY552 UT WOS:A1992JY55200003 PM 1418997 ER PT J AU SZEBERENYI, J ERHARDT, P CAI, H COOPER, GM AF SZEBERENYI, J ERHARDT, P CAI, H COOPER, GM TI ROLE OF RAS IN SIGNAL TRANSDUCTION FROM THE NERVE GROWTH-FACTOR RECEPTOR - RELATIONSHIP TO PROTEIN-KINASE-C, CALCIUM AND CYCLIC-AMP SO ONCOGENE LA English DT Article ID PC12 CELLS; TRK PROTOONCOGENE; ADENYLATE-CYCLASE; ONCOGENE PRODUCT; PHOSPHOLIPASE-C; 3T3 CELLS; DIFFERENTIATION; TRANSCRIPTION; ACTIVATION; INHIBITION AB A dominant inhibitory ras mutant (Ha-ras Asn-17) has been used to investigate the role of Ras in nerve growth factor (NGF)-mediated signal transduction in PC12 cells. Expression of Ha-Ras Asn-17 blocks neuronal differentiation of these cells in response to NGF treatment. The Ha-Ras Asn-17 block was bypassed by treatment with NGF plus dibutyryl cAMP or NGF plus the Ca2+ ionophore ionomycin, but not by NGF plus 12-tetradecanoyl phorbol acetate (TPA). Direct stimulation of the cAMP or Ca2+ pathways thus appeared to act synergistically with a Ras-independent NGF signaling pathway. This Ras-independent pathway was also distinct from protein kinase C, since its activity was not affected by protein kinase C down-regulation. It thus appears that NGF stimulation generates a Ras-independent intracellular signal that contributes to neuronal differentiation independently of the cAMP, Ca2+ or protein kinase C second messenger systems Since TPA did not bypass the Ha-Ras Asn-17 block to differentiation, protein kinase C also did not appear to be sufficient for Ras-dependent pathways mediating NGF-induced differentiation. Down-regulation experiments further indicated that protein kinase C was not required for NGF induction of early response genes via either Ras-dependent or Ras-independent pathways. Moreover, the formation of inositol phosphates and mobilization of intracellular calcium in response to NGF was not inhibited in PC12 cells expressing the Ha-Ras Asn-17 protein. Therefore, although calcium was able to bypass the Ha-Ras Asn-17 block to PC12 differentiation, Ras activity was not required for activation of phospholipase C in response to NGF. It thus appears that both Ras-dependent and Ras-independent signaling pathways contribute to NGF-induced PC12 cell differentiation independently of the cAMP, calcium and protein kinase C second messenger systems. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [R01 CA18689] NR 51 TC 49 Z9 49 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 1992 VL 7 IS 11 BP 2105 EP 2113 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA JW665 UT WOS:A1992JW66500002 PM 1331931 ER PT J AU GOLDMAN, MB MONSON, RR MALOOF, F AF GOLDMAN, MB MONSON, RR MALOOF, F TI BENIGN THYROID-DISEASES AND THE RISK OF DEATH FROM BREAST-CANCER SO ONCOLOGY LA English DT Article DE CARCINOGENESIS; BREAST CANCER; EPIDEMIOLOGY; HYPERTHYROIDISM; HYPOTHYROIDISM; MORTALITY; THYROID DISEASES ID SUPPLEMENTS; WOMEN AB A survey of the causes of death among women with benign thyroid disease was conducted to assess the risk of breast cancer mortality in thyroid patients. The study population was all women diagnosed with one of several types of thyroid disease at the Massachusetts General Hospital Thyroid Clinic from 1925 to 1974. A population-based comparison group was matched to the Clinic patients for age and socioeconomic status, resulting in a total of 9,520 matched pairs. A search of the Massachusetts mortality records located death certificates for 10.9% (1,039) of the Thyroid Clinic patients and 10.5% (995) of the comparison women. Cancer was the cause of death in 21% (218) of the Thyroid Clinic patients and 24% (239) of the comparison women. Fewer patients than comparison women died from cancers of the digestive organs (30.2 vs. 45.5%), but more patients died from thyroid cancer (3.7 vs. 0%), lymphatic and hematopoietic cancers (11.5 vs. 4.2%), and cancers of other sites (8.3 vs. 3.8%). Breast cancer deaths accounted for 21.6% of cancer deaths in the patients and 22.2% of cancer deaths in the comparison women. When specific thyroid diagnoses were considered, the percent of all deaths due to breast cancer ranged from 1.9 to 5.6%, compared to 5.3% in the comparison women. Of the diagnostic groups studied, patients with Hashimoto's thyroiditis had the lowest percent of deaths due to breast cancer, while those with nontoxic nodular goiter had the highest. C1 MASSACHUSETTS GEN HOSP,THYROID UNIT,BOSTON,MA 02114. RP GOLDMAN, MB (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [N01-CP-41060, N01-CB-84230] NR 21 TC 25 Z9 26 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY JI Oncology PD NOV-DEC PY 1992 VL 49 IS 6 BP 461 EP 466 PG 6 WC Oncology SC Oncology GA KD545 UT WOS:A1992KD54500011 PM 1465285 ER PT J AU RUBINFELD, RS PFISTER, RR STEIN, RM FOSTER, CS MARTIN, NF STOLERU, S TALLEY, AR SPEAKER, MG AF RUBINFELD, RS PFISTER, RR STEIN, RM FOSTER, CS MARTIN, NF STOLERU, S TALLEY, AR SPEAKER, MG TI SERIOUS COMPLICATIONS OF TOPICAL MITOMYCIN-C AFTER PTERYGIUM SURGERY SO OPHTHALMOLOGY LA English DT Article ID POSTOPERATIVE INSTILLATION; ULCERATION AB Background: The use of topical mitomycin (mitomycin-C) as a medical adjunct to pterygium and glaucoma surgery is increasing. Methods: The authors report on a series of 10 patients who experienced serious, vision-threatening complications associated with the use of this drug after pterygium surgery. Results: Complications included severe secondary glaucoma (4 patients), corneal edema (3 patients), corneal perforation (1 patient), corectopia (2 patients), iritis (8 patients), sudden onset mature cataract (2 patients), scleral calcification (1 patient) and incapacitating photophobia and pain (8 patients). Two patients required penetrating keratoplasties and a third required three lamellar keratoplasties. Another patient underwent four additional surgeries including a conjunctival Z-plasty, scleral patch grafting, and conjunctival autografting before his intractable pain and photophobia resolved 15 months after the original surgery. Because of these complications, 6 patients required a total of 20 return visits to the operating room after their original pterygium surgery. In 5 eyes, visual acuity remained at 20/200 or less. Three of the six patients with the most severe complications had concomitant chronic external diseases (rosacea [3 patients], ichthyosis [1 patient], keratitis sicca [1 patient]). Conclusion: The authors urge extreme caution in the use of mitomycin. If mitomycin is used, the lowest possible concentration should be applied for the shortest time period in an effort to avoid these complications. A prospective multicenter study of the ophthalmic use of this medication is needed. C1 GEORGETOWN UNIV,MED CTR,CTR SIGHT,WASHINGTON,DC 20007. BROOKWOOD MED CTR,EYE RES LABS,BIRMINGHAM,AL. NEW YORK EYE & EAR INFIRM,CORNEA SERV,NEW YORK,NY 10003. WASHINGTON UNIV,DEPT OPHTHALMOL,ST LOUIS,MO 63130. WASHINGTON HOSP CTR,DEPT OPHTHALMOL,WASHINGTON,DC 20010. UNIV TORONTO,DEPT OPHTHALMOL,TORONTO M5S 1A1,ONTARIO,CANADA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 26 TC 439 Z9 460 U1 1 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1992 VL 99 IS 11 BP 1647 EP 1654 PG 8 WC Ophthalmology SC Ophthalmology GA JY023 UT WOS:A1992JY02300010 PM 1454338 ER PT J AU LATINA, MA MELAMED, S MARCH, WF KASS, MA KOLKER, AE AF LATINA, MA MELAMED, S MARCH, WF KASS, MA KOLKER, AE TI GONIOSCOPIC ABINTERNO LASER SCLEROSTOMY - A PILOT-STUDY IN GLAUCOMA PATIENTS SO OPHTHALMOLOGY LA English DT Article ID YAG LASER; SURGERY AB Purpose: The purpose of this study is to evaluate the safety and efficacy of gonioscopic ab interno laser sclerostomy (GLS) in patients with glaucoma. Methods: The technique of GLS involves iontophoresis of methylene blue dye (1%) at the limbus to focally dye the sclera and to provide subsequent delivery of 10-musec pulsed laser energy to the dyed area through a goniolens. The laser emits at 660 nm, a wavelength that is maximally absorbed by the methylene blue dye. Patients were evaluated for fistula formation, intraocular pressure (IOP) reduction, and adverse sequelae. Thirty-eight treatments were performed in 35 eyes. Results: Successful complete sclerostomies were achieved in 21 eyes (55%), which was associated with an acute mean reduction in IOP of 23 mmHg. Mean preoperative IOP for all patients was 35 mmHg, and 1 hour after treatment it was reduced to 18.5 mmHg. In 4 of the 38 treatments, there was no acute IOP reduction, and these eyes were judged as failures. The mean follow-up time was 8.2 months with a maximum follow-up of 15 months. By 9 months, 50% of patients had an IOP of 22 mmHg or lower. The number of antiglaucoma medications decreased from 3.1 to 1.7 for all eyes over the 15-month follow-up period. Hyphemas (13%) were the only major complication, and these resolved spontaneously. In only one case did the IOP increase after the procedure. Conclusion: The results of this trial indicate that GLS is technically feasible, and preliminary results of IOP control are promising. C1 CHAIM SHEBA MED CTR,GOLDSCHLEGER EYE INST,IL-52621 TEL HASHOMER,ISRAEL. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63110. UNIV TEXAS,MED BRANCH,SCH MED,GALVESTON,TX 77550. RP LATINA, MA (reprint author), MASSACHUSETTS GEN HOSP,WELLMAN LABS,2ND FLOOR,BOSTON,MA 02114, USA. NR 17 TC 16 Z9 16 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 NOV PY 1992 VL 99 IS 11 BP 1736 EP 1744 PG 9 WC Ophthalmology SC Ophthalmology GA JY023 UT WOS:A1992JY02300025 PM 1454351 ER PT J AU SHIH, SL LIN, JCT LEE, HC BLICKMAN, JG AF SHIH, SL LIN, JCT LEE, HC BLICKMAN, JG TI UNUSUAL CAUSES OF OBSTRUCTIVE-JAUNDICE IN CHILDREN - DIAGNOSIS ON CT SO PEDIATRIC RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY AB Three cases are presented with unusual causes of obstructive jaundice diagnosed on abdominal CT in children under the age of 15 years. All the cases were initially examined by ultrasound which was inconclusive. CT studies were subsequently performed were diagnostic. These cases included hepatocellular carcinoma, a common bile duct web and duodenal hematoma. The first two cases were surgically confirmed, while the third case was proved by clinical follow-up. C1 MACKAY MEM HOSP,DEPT PEDIAT,TAIPEI,TAIWAN. MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV PEDIAT RADIOL,BOSTON,MA 02114. RP SHIH, SL (reprint author), MACKAY MEM HOSP,DEPT RADIOL,SECT 2,92 CHUNG SAN N RD,TAIPEI,TAIWAN. NR 12 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD NOV PY 1992 VL 22 IS 7 BP 512 EP 514 DI 10.1007/BF02012997 PG 3 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA JZ790 UT WOS:A1992JZ79000010 PM 1337201 ER PT J AU ZACHAZEWSKI, JE GEISSLER, G AF ZACHAZEWSKI, JE GEISSLER, G TI WHEN TO PRESCRIBE A KNEE BRACE SO PHYSICIAN AND SPORTSMEDICINE LA English DT Article AB Knee bracing can affect an athlete's performance or rehabilitation, and the decision to brace can have ethical and liability implications as well. When prescribing a brace, a clinician must take into account brace function, construction, and the type of support it can provide for the athlete's knee. Sports medicine professionals can ensure patient compliance by prescribing a comfortable, yet functional, brace and by letting them know what to realistically expect from wearing the device. RP ZACHAZEWSKI, JE (reprint author), MASSACHUSETTS GEN HOSP,SPORTS PHYS THERAPY,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 0091-3847 J9 PHYSICIAN SPORTSMED JI Physician Sportsmed. PD NOV PY 1992 VL 20 IS 11 BP 91 EP & PG 0 WC Primary Health Care; Orthopedics; Sport Sciences SC General & Internal Medicine; Orthopedics; Sport Sciences GA JX821 UT WOS:A1992JX82100012 ER PT J AU MICHEL, JL MADOFF, LC OLSON, K KLING, DE KASPER, DL AUSUBEL, FM AF MICHEL, JL MADOFF, LC OLSON, K KLING, DE KASPER, DL AUSUBEL, FM TI LARGE, IDENTICAL, TANDEM REPEATING UNITS IN THE C-PROTEIN ALPHA-ANTIGEN GENE, BCA, OF GROUP-B STREPTOCOCCI SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MOLECULAR SEQUENCE DATA; STREPTOCOCCUS-AGALACTIAE; BACTERIAL ANTIGENS; AMINO ACID SEQUENCE HOMOLOGY; REPETITIVE SEQUENCES ID COMPLETE NUCLEOTIDE-SEQUENCE; CARBOHYDRATE BINDING REGION; GROUP-A STREPTOCOCCUS; TYPE-6 M PROTEIN; REPETITIVE STRUCTURE; ESCHERICHIA-COLI; MEMBRANE ANCHOR; BETA-ANTIGEN; IGA RECEPTOR; EXPRESSION AB Group B Streptococcus (GBS) is the leading cause of neonatal sepsis and meningitis in the United States. The surface-associated C protein alpha antigen of GBS is thought to have a role in both virulence and immunity. We previously cloned the C protein alpha antigen structural gene (named bca for group B, C protein, alpha) into Escherichia coli. Western blots of both the native alpha antigen and the cloned gene product demonstrate a regularly laddered pattern of heterogeneous polypeptides. The nucleotide sequence of the bca locus reveals an open reading frame of 3060 nucleotides encoding a precursor protein of 108,705 Da. Cleavage of a putative signal sequence of 41 amino acids yields a mature protein of 104,106 Da. The 20,417-Da N-terminal region of the alpha antigen shows no homology to previously described protein sequences and is followed by a series of nine tandem repeating units that make up 74% of the mature protein. Each repeating unit is identical and consists of 82 amino acids with a molecular mass of 8665 Da, which is encoded by 246 nucleotides. The size of the repeating units corresponds to the observed size differences in the heterogeneous ladder of alpha C proteins expressed by GBS. The C-terminal region of the alpha antigen contains a membrane anchor domain motif that is shared by a number of Gram-positive surface proteins. The large region of identical repeating units in bca defines protective epitopes and may play a role in generating phenotypic and genotypic diversity of the alpha antigen. C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV INFECT DIS,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. RP MICHEL, JL (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,180 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI28500, AI00981, AI23339] NR 44 TC 110 Z9 112 U1 0 U2 5 PU NATL ACAD PRESS 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 NOV 1 PY 1992 VL 89 IS 21 BP 10060 EP 10064 DI 10.1073/pnas.89.21.10060 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800018 PM 1438195 ER PT J AU ARANDA, CMA SWANSON, JA LOOMIS, WP MILLER, SI AF ARANDA, CMA SWANSON, JA LOOMIS, WP MILLER, SI TI SALMONELLA-TYPHIMURIUM ACTIVATES VIRULENCE GENE-TRANSCRIPTION WITHIN ACIDIFIED MACROPHAGE PHAGOSOMES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHAGOSOME ACIDIFICATION; GENE EXPRESSION; PATHOGENESIS ID LYSOSOME FUSION; BACTERIAL VIRULENCE; TOLERANCE RESPONSE; MAMMALIAN-CELLS; PHOP-PHOQ; ACIDIFICATION; PROTEIN AB Survival of Salmonella typhimurium within macrophage phagosomes requires the coordinate expression of bacterial gene products. This report examines the contribution of phagosomal pH as a signal for expression of genes positively regulated by the S. typhimurium virulence regulators PhoP and PhoQ. Several hours after bacterial phagocytosis by murine bone marrow-derived macrophages, PhoP-activated gene transcription increased 50- to 77-fold. In contrast, no difference in PhoP-activated gene expression was observed after infection of cultured epithelial cells, suggesting that the membrane sensor PhoQ recognized signals unique to macrophage phagosomes. The increase in PhoP-regulated gene expression was abolished when macrophage culture medium contained NH4Cl or chloroquine, weak bases that raise the pH of acidic compartments. Measurements of pH documented that S. typhimurium delayed and attenuated acidification of its intracellular compartment. Phagosomes containing S. typhimurium required 4-5 hr to reach pH < 5.0. In contrast, within 1 hr vacuoles containing heat-killed bacteria were measured at pH < 4.5. The eventual acidification of phagosomes to pH < 5.0 correlated with the period of maximal PhoP-dependent gene expression. These observations implicate phagosome acidification as an intracellular inducer of PhoP-regulated gene expression and suggest that Salmonella survival is dependent on its ability to attenuate phagosome acidification. C1 HARVARD UNIV,SCH MED,DEPT ANAT & CELLULAR BIOL,BOSTON,MA 02115. RP ARANDA, CMA (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,FRUIT ST,BOSTON,MA 02114, USA. RI Swanson, Joel/P-4362-2014 OI Swanson, Joel/0000-0003-0900-8212 NR 36 TC 96 Z9 96 U1 3 U2 5 PU NATL ACAD PRESS 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 NOV 1 PY 1992 VL 89 IS 21 BP 10079 EP 10083 DI 10.1073/pnas.89.21.10079 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800022 ER PT J AU DATTA, R RUBIN, E SUKHATME, V QURESHI, S HALLAHAN, D WEICHSELBAUM, RR KUFE, DW AF DATTA, R RUBIN, E SUKHATME, V QURESHI, S HALLAHAN, D WEICHSELBAUM, RR KUFE, DW TI IONIZING-RADIATION ACTIVATES TRANSCRIPTION OF THE EGR1 GENE VIA CARG ELEMENTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE X-RAYS; EARLY GROWTH RESPONSE; SERUM RESPONSE ELEMENT ID SERUM RESPONSE ELEMENT; PROTEIN-KINASE-C; UPSTREAM REGULATORY SEQUENCES; GROWTH-FACTOR PATHWAYS; ZINC FINGER PROTEIN; LEUKEMIA-CELLS; PHORBOL ESTER; BINDING SITE; FOS ENHANCER; ACTIN GENES AB The present studies have examined the effects of ionizing radiation on control of the early growth response 1 (EGR1) gene. Exposure of human HL-525 cells to x-rays was associated with increases in EGR1 mRNA levels. Nuclear run-on assays showed that this effect is related at least in part to activation of EGR1 gene transcription. Sequences responsive to ionizing radiation-induced signals were determined by deletion analysis of the EGR1 promoter. The results demonstrate that x-ray inducibility of the EGR1 gene is conferred by a region containing six serum response or CC(A+T-rich)6GG (CArG) motifs. Further analysis confirmed that the region encompassing the three distal or upstream CArG elements is functional in the x-ray response. Moreover, this region conferred x-ray inducibility to a minimal thymidine kinase gene promoter. Taken together, these results indicate that ionizing radiation induces EGR1 transcription through CArG elements. C1 UNIV CHICAGO,HOWARD HUGHES MED INST,DEPT MED,CHICAGO,IL 60637. PRITZKER SCH MED,CHICAGO,IL 60637. UNIV CHICAGO,HOWARD HUGHES INST,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. RP DATTA, R (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115, USA. RI Hillyer, Nora/F-1745-2011 FU NCI NIH HHS [CA55241, CA41068] NR 48 TC 192 Z9 214 U1 0 U2 3 PU NATL ACAD PRESS 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 NOV 1 PY 1992 VL 89 IS 21 BP 10149 EP 10153 DI 10.1073/pnas.89.21.10149 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800036 PM 1332031 ER PT J AU CHANOCK, SJ FAUST, LP BARRETT, D BIZAL, C MALY, FE NEWBURGER, PE RUEDI, JM SMITH, RM BABIOR, BM AF CHANOCK, SJ FAUST, LP BARRETT, D BIZAL, C MALY, FE NEWBURGER, PE RUEDI, JM SMITH, RM BABIOR, BM TI O2(-) PRODUCTION BY LYMPHOCYTES-B LACKING THE RESPIRATORY BURST OXIDASE SUBUNIT P47PHOX AFTER TRANSFECTION WITH AN EXPRESSION VECTOR CONTAINING A P47PHOX CDNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; CELL-FREE SYSTEM; ADENINE-DINUCLEOTIDE PHOSPHATE; NEUTROPHIL CYTOCHROME-B; 2 CYTOSOLIC COMPONENTS; NADPH OXIDASE; POLYMORPHONUCLEAR LEUKOCYTES; SUPEROXIDE GENERATION; PLASMA-MEMBRANE; ACTIVATION AB The respiratory burst oxidase of phagocytes and B lymphocytes is a complicated enzyme that catalyzes the one-electron reduction of oxygen by NADPH. It is responsible for the O2- production that occurs when these cells are exposed to phorbol 12-myristate 13-acetate or other appropriate stimuli. The activity of this enzyme is greatly decreased or absent in patients with chronic granulomatous disease, an inherited disorder characterized by a severe defect in host defense against bacteria and fungi. In every chronic granulomatous disease patient studied to date, an abnormality has been found in a gene encoding one of four components of the respiratory burst oxidase: the membrane protein p22phox or gp91phox, or the cytosolic protein p47phox or p67phox. We report here that O2- production was partly restored to phorbol 12-myristate 13-acetate-stimulated Epstein-Barr virus-transformed B lymphocytes from a patient with p47phox-deficient chronic granulomatous disease by transfection with an expression plasmid containing a p47phox cDNA inserted in the sense direction. No detectable O2- was produced by untransfected p47phox-deficient lymphocytes or by p47phox-deficient lymphocytes transfected with an antisense plasmid. The finding that O2- can be produced by p47phox-deficient B lymphocytes after the transfer of a p47phox cDNA into the deficient cells suggests that this system could be useful for studying the function of mutant p47phox proteins in whole cells. C1 UNIV MASSACHUSETTS, SCH MED, DEPT PEDIAT, WORCESTER, MA 01655 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. UNIV CALIF SAN DIEGO, SCH MED, DEPT MED, LA JOLLA, CA 92093 USA. CHILDRENS HOSP MED CTR, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. NCI, PEDIAT BRANCH, FREDERICK, MD 21701 USA. RP CHANOCK, SJ (reprint author), SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. FU NIAID NIH HHS [AI-24838, AI-24227, AI-28479] NR 40 TC 46 Z9 46 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 1992 VL 89 IS 21 BP 10174 EP 10177 DI 10.1073/pnas.89.21.10174 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800041 PM 1332032 ER PT J AU ARUFFO, A KANNER, SB SGROI, D LEDBETTER, JA STAMENKOVIC, I AF ARUFFO, A KANNER, SB SGROI, D LEDBETTER, JA STAMENKOVIC, I TI CD22-MEDIATED STIMULATION OF T-CELLS REGULATES T-CELL RECEPTOR CD3-INDUCED SIGNALING SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CD22; CD45; SIALIC ACID; CARBOHYDRATE; ADHESION ID LEUKOCYTE-COMMON ANTIGEN; PROTEIN TYROSINE PHOSPHATASES; B-CELLS; PHOSPHOLIPASE C-GAMMA-1; ADHESION MOLECULE; CD45; PHOSPHORYLATION; ACTIVATION; EXPRESSION; KINASE AB Interaction between B lymphocytes and other cell types is mediated in part by the B-cell adhesion molecule CD22. Recent work has suggested one of the T-cell ligands of B cells to be CD45RO, an isoform of the receptor-linked phosphotyrosine phosphatase CD45. Here we demonstrate direct interaction between CD22 and several isoforms of CD45, including CD45RO, and propose that the interaction may participate in regulation of lymphocyte signaling. Cross-linking of CD3 and CD22 T-cell ligands with anti-CD3 antibody and soluble CD22 is shown to block anti-CD3-induced intracellular calcium increase and to inhibit tyrosine phosphorylation of phospholipase Cgamma1. These effects are consistent with those observed upon coligation of CD3 and CD45 with antibody, providing support to the possibility that ligand-mediated stimulation of CD45 may result in modulation of substrate phosphorylation and lymphocyte activation. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129. PATHOL RES,BOSTON,MA 02129. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NCI NIH HHS [CA55735]; NIGMS NIH HHS [GM43257] NR 47 TC 95 Z9 95 U1 0 U2 3 PU NATL ACAD PRESS 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 NOV 1 PY 1992 VL 89 IS 21 BP 10242 EP 10246 DI 10.1073/pnas.89.21.10242 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800055 PM 1438211 ER PT J AU MYERS, MG BACKER, JM SUN, XJ SHOELSON, S HU, P SCHLESSINGER, J YOAKIM, M SCHAFFHAUSEN, B WHITE, MF AF MYERS, MG BACKER, JM SUN, XJ SHOELSON, S HU, P SCHLESSINGER, J YOAKIM, M SCHAFFHAUSEN, B WHITE, MF TI IRS-1 ACTIVATES PHOSPHATIDYLINOSITOL 3'-KINASE BY ASSOCIATING WITH SRC HOMOLOGY-2 DOMAINS OF P85 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR TYROSINE KINASES; GROWTH-FACTOR RECEPTORS; INSULIN-RECEPTOR; SIGNAL TRANSDUCTION; PROTEIN; PHOSPHOTYROSINE; SEQUENCE; PI3-KINASE; EXPRESSION; SUBSTRATE AB IRS-1 is an insulin receptor substrate that undergoes tyrosine phosphorylation and associates with the phosphatidylinositol (PtdIns) 3'-kinase immediately after insulin stimulation. Recombinant IRS-1 protein was tyrosine phosphorylated by the insulin receptor in vitro and associated with the PtdIns 3'-kinase from lysates of quiescent 3T3 fibroblasts. Bacterial fusion proteins containing the src homology 2 domains (SH2 domains) of the 85-kDa subunit (p85) of the PtdIns 3'-kinase bound quantitatively to tyrosine phosphorylated, but not unphosphorylated, IRS-1, and this association was blocked by phosphotyrosine-containing synthetic peptides. Moreover, the phosphorylated peptides and the SH2 domains each inhibited binding of PtdIns 3'-kinase to IRS-1. Phosphorylated IRS-1 activated PtdIns 3'-kinase in anti-p85 immunoprecipitates in vitro, and this activation was blocked by SH2 domain fusion proteins. These data suggest that the interaction between PtdIns 3'-kinase and IRS-1 is mediated by tyrosine phosphorylated motifs on IRS-1 and the SH2 domains of p85, and IRS-1 activates PtdIns 3'-kinase by binding to the SH2 domains of p85. Thus, IRS-1 likely serves to transmit the insulin signal by binding and regulating intracellular enzymes containing SH2 domains. C1 HARVARD UNIV,SCH MED,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM CELLULAR & DEV BIOL,BOSTON,MA 02115. NYU,DEPT PHARMACOL,NEW YORK,NY 10016. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. OI Hu, Patrick/0000-0002-5611-8062 FU NCI NIH HHS [CA 34722]; NIDDK NIH HHS [DK-38712, DK-43808] NR 25 TC 382 Z9 384 U1 1 U2 12 PU NATL ACAD PRESS 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 NOV 1 PY 1992 VL 89 IS 21 BP 10350 EP 10354 DI 10.1073/pnas.89.21.10350 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800077 PM 1332046 ER PT J AU EPSTEIN, RJ DRUKER, BJ ROBERTS, TM STILES, CD AF EPSTEIN, RJ DRUKER, BJ ROBERTS, TM STILES, CD TI SYNTHETIC PHOSPHOPEPTIDE IMMUNOGENS YIELD ACTIVATION-SPECIFIC ANTIBODIES TO THE C-ERBB-2 RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TYROSINE KINASES; ONCOGENES; PHOSPHORYLATION; BREAST NEOPLASMS ID HUMAN-BREAST-CANCER; AUTOPHOSPHORYLATION SITES; TYROSINE PHOSPHORYLATION; NEU ONCOGENE; PROTEIN; EXPRESSION; AMPLIFICATION; CARCINOMA; HER2/NEU; KINASE AB We inoculated rabbits with synthetic phosphopeptides, duplicating a major autophosphorylation site of the c-erbB-2 protooncogene product. The rabbits produced antisera that, after reverse immunoaffinity purification, selectively recognize the erbB-2 protein in its enzymatically active configuration. These anti-phosphopeptide antisera identify a subset of erbB-2-positive human cell lines wherein the protein is constitutively active as a tyrosine kinase. Synthetic phosphopeptides incorporating informative protein phosphorylation sites may prove useful for generating antibodies that indicate the activation state of additional tyrosine kinases and perhaps other proteins phosphorylated on serine and threonine residues. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RP EPSTEIN, RJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 01422, CA 56503]; NICHD NIH HHS [HD 24926] NR 34 TC 55 Z9 55 U1 0 U2 0 PU NATL ACAD PRESS 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 NOV 1 PY 1992 VL 89 IS 21 BP 10435 EP 10439 DI 10.1073/pnas.89.21.10435 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JW798 UT WOS:A1992JW79800094 PM 1359539 ER PT J AU HUFF, FJ GROWDON, JH CORKIN, S AF HUFF, FJ GROWDON, JH CORKIN, S TI DETERIORATION ON THE BLESSED INFORMATION-MEMORY-CONCENTRATION TEST IN ALZHEIMERS-DISEASE SO PSYCHIATRY RESEARCH LA English DT Letter C1 UNIV MED & DENT NEW JERSEY,DEPT NEUROL,JERSEY CITY,NJ. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02114. MIT,DEPT BRAIN & COGNIT SCI,CAMBRIDGE,MA 02139. NR 4 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV PY 1992 VL 44 IS 2 BP 167 EP 168 DI 10.1016/0165-1781(92)90050-D PG 2 WC Psychiatry SC Psychiatry GA KF251 UT WOS:A1992KF25100008 ER PT J AU STERN, RG MOHS, RC AF STERN, RG MOHS, RC TI DETERIORATION ON THE BLESSED INFORMATION-MEMORY-CONCENTRATION TEST IN ALZHEIMERS-DISEASE - REPLY SO PSYCHIATRY RESEARCH LA English DT Letter RP STERN, RG (reprint author), BRONX VET ADM MED CTR,MT SINAI SCH MED,PSYCHIAT SERV,NEW YORK,NY, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV PY 1992 VL 44 IS 2 BP 168 EP 168 DI 10.1016/0165-1781(92)90051-4 PG 1 WC Psychiatry SC Psychiatry GA KF251 UT WOS:A1992KF25100009 ER PT J AU SMALL, GW STERN, CE MANDELKERN, MA FAIRBANKS, LA MIN, CA GUZE, BH AF SMALL, GW STERN, CE MANDELKERN, MA FAIRBANKS, LA MIN, CA GUZE, BH TI RELIABILITY OF DRAWING REGIONS OF INTEREST FOR POSITRON EMISSION TOMOGRAPHIC DATA SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE INTERRATER RELIABILITY; CEREBRAL GLUCOSE METABOLIC RATE; FLUORODEOXYGLUCOSE ID ALZHEIMERS-DISEASE; DEMENTIA; BRAIN AB We determined interrater reliability for two raters who independently used a standard protocol to draw regions of interest (ROIs) on F-18 fluorodeoxyglucose positron emission tomographic data acquired from eight patients with mild to moderate memory impairment. Intraclass correlation coefficients for region sizes (total pixel number) varied among anatomical ROIs (R(I)s from 0.324 to 0.935). However, correlations calculated from relative metabolic rates (normalized average counts) were consistently high (R(I) greater-than-or-equal-to 0.954). The raters also showed high agreement for region recognition on each image plane (kappa = 0.978). These results suggest that rater disagreements in ROI margins have minimal impact on average count densities used to calculate metabolic rates. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. VET AFFAIRS MED CTR,PET FACIL,LOS ANGELES,CA. RP SMALL, GW (reprint author), UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,760 WESTWOOD PLAZA,LOS ANGELES,CA 90024, USA. FU NIMH NIH HHS [1 K07 MH00912, 1R29 MH46424] NR 16 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV PY 1992 VL 45 IS 3 BP 177 EP 185 DI 10.1016/0925-4927(92)90025-Y PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA KG096 UT WOS:A1992KG09600004 PM 1484909 ER PT J AU STARK, P JACOBSON, F SHAFFER, K AF STARK, P JACOBSON, F SHAFFER, K TI STANDARD IMAGING IN SILICOSIS AND COAL-WORKERS PNEUMOCONIOSIS SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP STARK, P (reprint author), BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115, USA. NR 6 TC 19 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 1992 VL 30 IS 6 BP 1147 EP 1154 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JR526 UT WOS:A1992JR52600004 PM 1410305 ER PT J AU MCLOUD, TC AF MCLOUD, TC TI CONVENTIONAL RADIOGRAPHY IN THE DIAGNOSIS OF ASBESTOS-RELATED DISEASE SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID INFILTRATIVE LUNG-DISEASE; PARIETAL PLEURAL PLAQUES; COMPUTED-TOMOGRAPHY; PULMONARY ASBESTOSIS; ROUNDED ATELECTASIS; EXPOSURE; POPULATION; EFFUSION; MESOTHELIOMA; PREVALENCE C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. RP MCLOUD, TC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 58 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 1992 VL 30 IS 6 BP 1177 EP 1189 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JR526 UT WOS:A1992JR52600006 PM 1410307 ER PT J AU MCLOUD, TC AF MCLOUD, TC TI OCCUPATIONAL LUNG-DISEASE - PREFACE SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Editorial Material RP MCLOUD, TC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 1992 VL 30 IS 6 BP R9 EP R9 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JR526 UT WOS:A1992JR52600001 ER PT J AU WOLF, GL AF WOLF, GL TI INDIRECT LYMPHOGRAPHY WITH RADIOPAQUE NANOPARTICULATES SO RADIOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1992 VL 185 SU S BP 115 EP 115 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JW377 UT WOS:A1992JW37700083 ER PT J AU HAYES, DF AF HAYES, DF TI FINE-NEEDLE ASPIRATION AND FLOW-CYTOMETRY FOR EVALUATION OF PRIMARY BREAST-CANCER SO RADIOLOGY LA English DT Editorial Material DE EDITORIALS; BREAST NEOPLASMS, DIAGNOSIS; BREAST NEOPLASMS, STAGING ID PROGNOSTIC FACTORS; CLINICAL-TRIAL; MORTALITY; MASTECTOMY; CARCINOMA; PLOIDY C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP HAYES, DF (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR BREAST EVALUAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 31 TC 2 Z9 2 U1 2 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1992 VL 185 IS 2 BP 337 EP 338 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JV360 UT WOS:A1992JV36000002 PM 1410333 ER PT J AU YODER, IC AF YODER, IC TI DIAGNOSIS OF UTERINE ANOMALIES - RELATIVE ACCURACY OF MR IMAGING, ENDOVAGINAL SONOGRAPHY, AND HYSTEROSALPINGOGRAPHY SO RADIOLOGY LA English DT Editorial Material DE UTERUS, ABNORMALITIES; UTERUS, MR; UTERUS, RADIOGRAPHY; UTERUS US ID MANAGEMENT RP YODER, IC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 10 TC 8 Z9 10 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1992 VL 185 IS 2 BP 343 EP 343 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JV360 UT WOS:A1992JV36000005 PM 1410336 ER PT J AU HARRIS, NL AF HARRIS, NL TI THE RELATIONSHIP BETWEEN HODGKINS-DISEASE AND NON-HODGKINS-LYMPHOMA SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE HODGKINS DISEASE; NON-HODGKINS LYMPHOMA; COMPOSITE LYMPHOMA; TRANSFORMATION OF LYMPHOMAS; RICHTERS SYNDROME RP HARRIS, NL (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114, USA. NR 0 TC 35 Z9 37 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 1992 VL 9 IS 4 BP 304 EP 310 PG 7 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA JY633 UT WOS:A1992JY63300010 PM 1480853 ER PT J AU SCULLY, RE AF SCULLY, RE TI PATHOLOGY OF LEIOMYOMAS SO SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY LA English DT Article RP SCULLY, RE (reprint author), MASSACHUSETTS GEN HOSP,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0734-8630 J9 SEMIN REPROD ENDOCR JI Semin. Reprod. Endocrinol. PD NOV PY 1992 VL 10 IS 4 BP 325 EP 331 DI 10.1055/s-2007-1018890 PG 7 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA KA591 UT WOS:A1992KA59100006 ER PT J AU MIHM, MC BARNHILL, RL SOBER, AJ HERNANDEZ, MH AF MIHM, MC BARNHILL, RL SOBER, AJ HERNANDEZ, MH TI PRECURSOR LESIONS OF MELANOMA - DO THEY EXIST SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article DE MELANOMA PRECURSOR; DYSPLASTIC NEVUS; CONGENITAL NEVUS; LENTIGO-MALIGNA; MELANOCYTIC HYPERPLASIA; MALIGNANT MELANOMA AB The question of whether definite precursors to melanoma exist is answered in the affirmative. Three cutaneous lesions likely to be such precursors are described and discussed as to their clinical and histologic appearance and incidence. Additionally, a type of conjunctival melanosis that has been associated with malignant melanoma of the conjunctiva is discussed and an attempt is made to define it; a proposed classification of this entity is reviewed. Basic approaches to management and analysis of precursor lesions are elaborated. RP MIHM, MC (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV DERMATOPATHOL,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD NOV-DEC PY 1992 VL 8 IS 6 BP 358 EP 365 DI 10.1002/ssu.2980080605 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA JZ062 UT WOS:A1992JZ06200004 PM 1439445 ER PT J AU KOROSHETZ, WJ AF KOROSHETZ, WJ TI NEUROPROTECTIVE EFFECTS OF CARVEDILOL, A NEW ANTIHYPERTENSIVE AGENT, IN CULTURED RAT CEREBELLAR NEURONS AND IN GERBIL GLOBAL BRAIN ISCHEMIA - COMMENT SO STROKE LA English DT Editorial Material RP KOROSHETZ, WJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02114, USA. NR 4 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 NOV PY 1992 VL 23 IS 11 BP 1635 EP 1636 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA JW348 UT WOS:A1992JW34800021 ER PT J AU LESSELL, S AF LESSELL, S TI PEDIATRIC PSEUDOTUMOR CEREBRI (IDIOPATHIC INTRACRANIAL HYPERTENSION) SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE CORTICOSTEROIDS; DRUG TOXICITY; INTRACRANIAL HYPERTENSION MOTILITY; OPTIC NERVE SHEATH FENESTRATION; PAPILLEDEMA; PEDIATRIC PSEUDOTUMOR CEREBRI; PSEUDOTUMOR CEREBRI; THYROID REPLACEMENT; VITAMIN DEFICIENCY ID SYSTEMIC LUPUS-ERYTHEMATOSUS; INTRA-CRANICAL HYPERTENSION; NALIDIXIC-ACID THERAPY; TUMOR CEREBRI; VISUAL-LOSS; VITAMIN-A; CYSTIC-FIBROSIS; FOLLOW-UP; CHILDHOOD; DEFICIENCY AB This review focuses on the features of pseudotumor cerebri in the pediatric age group. There is no sex predilection in children, and obesity does not appear to be an important factor. Infants and young children may present with irritability, apathy, or somnolence, rather than headache. Dizziness and ataxia may also occur. Papilledema is infrequently noted in pediatric patients if the fontanelles are open or the sutures are split. Pre-adolescents appear more likely than adults or adolescents to have manifestations of their pseudotumor cerebri other than headache and papilledema, including lateral rectus pareses, vertical strabismus, facial paresis, back and neck pain. Among the etiologies that are particularly pertinent to children are tetracycline therapy, malnutrition or renutrition, and the correction of hypothyroidism. Children with pseudotumor cerebri are at risk for visual loss and their visual function must be closely monitored. Surgical intervention is imperative when vision is threatened. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,NEUROOPHTHALMOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 128 TC 125 Z9 125 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD NOV-DEC PY 1992 VL 37 IS 3 BP 155 EP 166 DI 10.1016/0039-6257(92)90134-F PG 12 WC Ophthalmology SC Ophthalmology GA JZ499 UT WOS:A1992JZ49900001 PM 1475750 ER EF