FN Thomson Reuters Web of Science™ VR 1.0 PT J AU HERSCH, S JONES, R KOROSHETZ, W QUAID, K AF HERSCH, S JONES, R KOROSHETZ, W QUAID, K TI THE NEUROGENETICS GENIE - TESTING FOR THE HUNTINGTONS-DISEASE MUTATION SO NEUROLOGY LA English DT Review ID REPEAT LENGTH; CHOREA; ONSET; EXPERIENCE; EXPANSION; RISK C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA. INDIANA UNIV,SCH MED,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. RP HERSCH, S (reprint author), EMORY UNIV,SCH MED,DEPT NEUROL,1639 PIERCE DR,SUITE 6000,ATLANTA,GA 30322, USA. FU NINDS NIH HHS [NS01624] NR 26 TC 31 Z9 31 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1994 VL 44 IS 8 BP 1369 EP 1373 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA PB152 UT WOS:A1994PB15200001 PM 7914682 ER PT J AU PRIVITERA, MD TREIMAN, DM PLEDGER, GW SAHLROOT, JT HANDFORTH, A LINDE, MS FRANCE, CR CEREGHINO, JJ MCCUTCHEN, CB WOOD, JH AF PRIVITERA, MD TREIMAN, DM PLEDGER, GW SAHLROOT, JT HANDFORTH, A LINDE, MS FRANCE, CR CEREGHINO, JJ MCCUTCHEN, CB WOOD, JH TI DEZINAMIDE FOR PARTIAL SEIZURES - RESULTS OF AN N-OF-1 DESIGN TRIAL SO NEUROLOGY LA English DT Article ID CIGARETTE-SMOKING AB Background. Dezinamide (DZM, ADD 94057) is a potential antiepileptic drug that binds to the voltage-sensitive sodium channel and showed preliminary evidence of efficacy and safety in an open-label study. Methods. Our double-blind, placebo-controlled trial at two sites used an n-of-1 (single-patient) design. All 15 patients had medically intractable partial-onset seizures and were comedicated with phenytoin (PHT) only. Treatment was for six and week periods (three active paired with three placebo in random sequence). Assuming nonlinear kinetics, we used an initial pharmacokinetic profile to estimate dosages for reaching target plasma concentrations of DZM. Results. Statistically significant seizure reduction was found by both a randomization test (p = 0.0025) and a signed rank test (p = 0.048). Median seizure frequency decreased 37.9%, and 40% of patients had >50% seizure reduction, both compared with placebo. Pharmacokinetic predictions were not accurate; mean plasma concentrations fell well below target values. Plasma PHT concentrations increased (mean = 17.1%) during DZM treatment. The most common adverse experiences were fatigue, light-headedness, and abnormal gait; five patients required DZM dosage reductions. Conclusions. DZM showed minimal clinical toxicity and significant efficacy despite lower plasma concentrations than predicted by pharmacokinetics. This trial establishes the suitability of the n-of-1 design to investigational antiepileptie drug trials. C1 UNIV CALIF LOS ANGELES,MED CTR,DEPT NEUROL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,WADSWORTH DIV,LOS ANGELES,CA. NINCDS,EPILEPSY BRANCH,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARM,RICHMOND,VA 23298. RP PRIVITERA, MD (reprint author), UNIV CINCINNATI,MED CTR,DEPT NEUROL 525,CINCINNATI,OH 45267, USA. FU NINDS NIH HHS [NINDS N01-NS-7-2328, NINDS N01-NS-8-2306] NR 12 TC 10 Z9 10 U1 1 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1994 VL 44 IS 8 BP 1453 EP 1458 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA PB152 UT WOS:A1994PB15200018 PM 8058148 ER PT J AU REBECK, GW PERLS, TT WEST, HL SODHI, P LIPSITZ, LA HYMAN, BT AF REBECK, GW PERLS, TT WEST, HL SODHI, P LIPSITZ, LA HYMAN, BT TI REDUCED APOLIPOPROTEIN EPSILON-4 ALLELE FREQUENCY IN THE OLDEST-OLD ALZHEIMERS PATIENTS AND COGNITIVELY NORMAL INDIVIDUALS SO NEUROLOGY LA English DT Note ID E POLYMORPHISM; TYPE-4 ALLELE; DISEASE AB Recent genetic studies show that the apolipoprotein E epsilon 4 allele (ApoE-epsilon 4) is a risk factor for Alzheimer's disease (AD). If ApoE-epsilon 4 individuals develop AD as they get older, we would expect a decrease in ApoE-epsilon 4 allele frequency with increasing age. We found a marked decline in ApoE-epsilon 4 allele frequency with advancing age in both AD and cognitively normal controls (p < 0.003), although in all age groups the ApoE-epsilon 4 allele was overrepresented (p < 0.0001). Nonetheless, a few cognitively normal nonagenarians were ApoE-epsilon 4 positive. Thus, our data support two new conclusions: 1) the ApoE-epsilon 4 associated risk for AD is age-dependent, probably due to censoring by the earlier development of AD in ApoE-epsilon 4 individuals, and (2) despite the ApoE-epsilon 4 associated risk for AD, it is possible to reach extreme old age with normal cognition. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HEBREW REHABIL CTR AGED,BOSTON,MA 02131. FU NIA NIH HHS [AG05598, AG08487, P50AG05134] NR 10 TC 167 Z9 168 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1994 VL 44 IS 8 BP 1513 EP 1516 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA PB152 UT WOS:A1994PB15200031 PM 8058160 ER PT J AU CHYNN, EW CHYNN, KY DIGIACINTO, GV AF CHYNN, EW CHYNN, KY DIGIACINTO, GV TI CYSTIC LUMBAR MENINGIOMA PRESENTING AS A RING ENHANCING LESION ON MRI SO NEURORADIOLOGY LA English DT Article DE MENINGIOMA; CYSTIC; INTRASPINAL TUMOR; RING ENHANCING; MRI; GD-DTPA ID PATHOLOGICAL CORRELATION AB We report a cystic lumbar meningioma which presented as a ring enhancing lesion on MRI. C1 COLUMBIA UNIV COLL PHYS & SURG,ST LUKES ROOSEVELT HOSP CTR,DEPT DIAGNOST RADIOL,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT NEUROSURG,NEW YORK,NY 10032. RP CHYNN, EW (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD AUG PY 1994 VL 36 IS 6 BP 460 EP 461 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA PB567 UT WOS:A1994PB56700013 PM 7991092 ER PT J AU CATANIA, MV LANDWEHRMEYER, GB TESTA, CM STANDAERT, DG PENNEY, JB YOUNG, AB AF CATANIA, MV LANDWEHRMEYER, GB TESTA, CM STANDAERT, DG PENNEY, JB YOUNG, AB TI METABOTROPIC GLUTAMATE RECEPTORS ARE DIFFERENTIALLY REGULATED DURING DEVELOPMENT SO NEUROSCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; LONG-TERM DEPRESSION; RAT-BRAIN; MESSENGER-RNA; POSTNATAL-DEVELOPMENT; SIGNAL TRANSDUCTION; CEREBELLAR CORTEX; PHARMACOLOGICAL CHARACTERIZATION; BINDING-SITES; EXPRESSION AB The postnatal expression of metabotropic glutamate receptors was studied in rat brain by in situ hybridization and autoradiographic binding techniques. The messenger RNAs encoding five metabotropic glutamate receptor subtypes named mGluR1-5 had distinct regional and temporal expression profiles. mGluR1, mGluR2 and mGluR4 messenger RNA expression was low at birth and increased during postnatal development. In contrast, mGluR3 and mGluR5 were highly expressed at birth and decreased during maturation to adult levels of expression. [H-3]Glutamate binding competition studies in developing brain disclosed the presence of two types of binding sites with the pharmacological properties of metabotropic glutamate receptors, having high (metabotropic type-1 binding sites; K-1 = 8 nM) and low affinity (metabotropic type-2 binding sites; K-1 = 50 mu M) for quisqualic acid, as in adult rat brain. The densities of metabotropic binding sites changed during development in a complex, regionally specific fashion. Metabotropic type-1 binding sites were present at low levels at birth and gradually increased during the second postnatal week. In the striatum, globus pallidus and cerebellar granule layer, the increase in density of metabotropic type-1 binding sites was transient but persisted in the cerebellar molecular layer. In contrast, metabotropic type-2 binding sites were present at high densities in most regions in the first postnatal week and decreased during the second and third week, particularly in the thalamic reticular nucleus and globus pallidus. Only in the external cortex did both metabotropic type-1 and metabotropic type-2 binding sites increase during development. A striking correspondence between the temporal pattern of expression of specific metabotropic glutamate receptor transcripts and metabotropic binding sites was observed in the reticular nucleus of the thalamus (mGluR3; metabotropic type-2 binding sites) and cerebellum (mGluR1; metabotropic type-1 binding sites) suggesting early translation of these metabotropic glutamate receptor messenger RNAs into receptor proteins. In other regions the relationship between messenger RNA expression and binding sites was less direct: comparison between expression of metabotropic glutamate receptor messenger RNA and binding sites suggests both a pre- and postsynaptic location of some receptor subtypes. These data imply a functional role of mGluR3 and mGluR5 during synaptogenesis and maintenance of adult synapses and of mGluR1, mGluR2 and mGluR4 in mature synaptic transmission. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Catania, Maria Vincenza/E-2627-2017; OI Catania, Maria Vincenza/0000-0002-9329-8517; Standaert, David/0000-0003-2921-8348 NR 46 TC 182 Z9 184 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD AUG PY 1994 VL 61 IS 3 BP 481 EP 495 DI 10.1016/0306-4522(94)90428-6 PG 15 WC Neurosciences SC Neurosciences & Neurology GA PA794 UT WOS:A1994PA79400008 PM 7969925 ER PT J AU BALDESSARINI, RJ CAMPBELL, A BENJONATHAN, N ELLINGBOE, J ZONG, RS NEUMEYER, JL AF BALDESSARINI, RJ CAMPBELL, A BENJONATHAN, N ELLINGBOE, J ZONG, RS NEUMEYER, JL TI EFFECTS OF APORPHINE ISOMERS ON RAT PROLACTIN SO NEUROSCIENCE LETTERS LA English DT Article DE ANTIPSYCHOTIC; APORPHINE; DOPAMINE; PARTIAL AGONIST; PROLACTIN; RECEPTOR; STEREOISOMER ID DOPAMINE; BRAIN AB S(+)-aporphines are partial agonists at D-2 dopamine receptors. High selectivity of anti-dopaminergic action in limbic vs. extrapyramidal regions of rat brain and lack of induction of dopaminergic supersensitivity have suggested their potential as atypical antipsychotic drugs. Now, in testing for effects on circulating prolactin, a typical D-2 antagonist haloperidol elevated, and potent agonist R(-)-11-hydroxy-N-propylnoraporphine lowered, serum prolactin levels in gentled male rats, while S(+)-N-propylnorapomorphine and its 11-monohydroxy analog had little or no effect, even at high doses. Lack of hyperprolactinemia adds to characteristics of S(+)-aporphines that are desirable in improved antipsychotics. C1 HARVARD UNIV,SCH MED,CONSOLIDATED DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH MED,NEUROSCI PROGRAM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MCLEAN DIV,MAILMAN RES CTR,BELMONT,MA. MASSACHUSETTS GEN HOSP,MCLEAN DIV,ALCOHOL & ADDICT RES CTR,BELMONT,MA. UNIV CINCINNATI,DEPT ANAT & CELL BIOL,CINCINNATI,OH 45267. NORTHEASTERN UNIV,COLL PHARM & ALLIED HLTH PROFESS,MED CHEM SECT,BOSTON,MA 02115. RES BIOCHEM INT,NATICK,MA. FU NIMH NIH HHS [MH-47370, MH-31154, MH-34006] NR 16 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 1 PY 1994 VL 176 IS 2 BP 269 EP 271 DI 10.1016/0304-3940(94)90098-1 PG 3 WC Neurosciences SC Neurosciences & Neurology GA PE808 UT WOS:A1994PE80800033 PM 7830962 ER PT J AU TAKAHASHI, LK KIM, H AF TAKAHASHI, LK KIM, H TI INTRACRANIAL ACTION OF CORTICOSTERONE FACILITATES THE DEVELOPMENT OF BEHAVIORAL-INHIBITION IN THE ADRENALECTOMIZED PREWEANLING RAT SO NEUROSCIENCE LETTERS LA English DT Article DE PREWEANLING RAT; BEHAVIORAL INHIBITION; FREEZING; ULTRASONIC VOCALIZATION; DEVELOPMENT; CONSPECIFIC THREAT; ADRENAL STEROID; CORTICOSTERONE ID REGULATE POSTNATAL-DEVELOPMENT; DENTATE-GYRUS; GLUCOCORTICOID RECEPTOR; ONTOGENY; BRAIN; HIPPOCAMPUS; PITUITARY; STRESS; MATURATION; EXPRESSION AB We tested the hypothesis that in preweanling rats central administration of exogenous corticosterone (CORT) is sufficient to facilitate the development of behavioral inhibition. 28-gauge cannulae containing varying concentrations of CORT (0, 25, 50 and 100%) were implanted unilaterally into the lateral ventricles of 9-day-old rat pups. After a 24-h postoperative recovery period, pups were adrenalectomized. At 14 days of age, pups were tested for behavioral inhibition which consisted of removing the pup from the nest and exposing it to an unfamiliar adult male rat. Pups implanted with cannulae containing 0, 25 and 50% concentrations of CORT spent significantly less time in freezing postures than pups implanted with cannulae containing 100% CORT. These freezing pups also tended to emit fewer ultrasonic vocalizations than pups in the other three implant conditions, albeit the level obtained was not statistically significant. RIAs indicated that, in general, hormone-filled cannulae produced no detectable concentrations of plasma CORT on the day of the test or on days preceding testing. Results suggest that in the early postnatal period endogenous CORT acts centrally to facilitate the development of neural pathways involved in the ontogenetic expression of behavioral inhibition. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP TAKAHASHI, LK (reprint author), UNIV WISCONSIN,SCH MED,DEPT PSYCHIAT,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NIMH NIH HHS [MH-43986] NR 42 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 1 PY 1994 VL 176 IS 2 BP 272 EP 276 DI 10.1016/0304-3940(94)90099-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA PE808 UT WOS:A1994PE80800034 PM 7830963 ER PT J AU MADIANOS, PN PAPAPANOU, PN SOCRANSKY, SS DAHLEN, G SANDROS, J AF MADIANOS, PN PAPAPANOU, PN SOCRANSKY, SS DAHLEN, G SANDROS, J TI HOST-RELATED GENOTYPIC HETEROGENEITY OF PORPHYROMONAS-GINGIVALIS STRAINS IN THE BEAGLE DOG SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE CLONAL TYPE; RIBOTYPE; FINGER PRINTING; PORPHYROMONAS GINGIVALIS; BEAGLE DOG; RESTRICTION ENDONUCLEASE ID RESTRICTION ENDONUCLEASE ANALYSIS; PIGMENTED BACTEROIDES STRAINS; EPITHELIAL-CELLS; SUBGINGIVAL MICROORGANISMS; ACTINOMYCES-VISCOSUS; DNA; VIRULENCE; ATTACHMENT; ADHERENCE; PORPHYROMONAS-(BACTEROIDES)-GINGIVALIS AB The present investigation explored the genotypic heterogeneity of Porphyromonas gingivalis using restriction endonuclease analysis and ribotyping of 64 P. gingivalis isolates, recovered from the periodontal pockets of 3 beagle dogs, 2 of which were reared together. The isolates originated from both healthy and periodontal disease affected sites and thereby enabled the study of bacterial genotype with respect to (i) individual host, (ii) ecological niche (site within host) and (iii) level of periodontal health. Whole genomic DNA was extracted from each isolate and digested by the restriction endonuclease KpnI. Digestion fragments were separated by electrophoresis and transferred onto nylon membranes. The blots were hybridized with a digoxigenin-labeled 16S rDNA probe, and hybridization bands were detected using an anti-digoxigenin antibody conjugated with alkaline phosphatase and enhanced chemiluminescence. Fourteen genomic fingerprints and 13 ribotypes were observed among the 64 isolates. As many as 8 distinct fingerprints were detected within a single host and up to 4 fingerprints within a single periodontal pocket. The dogs reared together shared 2 common clonal types but also exhibited clonal types unique to each dog. No clear association between clonal type and periodontal health status could be made. The results revealed an extensive intra-host genotypic heterogeneity of P. gingivalis strains in the beagle dog and indicated that ribotyping was a sensitive method for differentiating clonal types within species. C1 GOTHENBURG UNIV,FAC ODONTOL,DEPT PERIODONTOL,S-41390 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,FAC ODONTOL,DEPT ORAL MICROBIOL,GOTHENBURG,SWEDEN. FORSYTH DENT CTR,BOSTON,MA 02115. ROCKEFELLER UNIV,MOLEC INFECT DIS LAB,NEW YORK,NY 10021. FU NIDCR NIH HHS [DE-04881] NR 48 TC 6 Z9 7 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD AUG PY 1994 VL 9 IS 4 BP 241 EP 247 DI 10.1111/j.1399-302X.1994.tb00065.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA NV278 UT WOS:A1994NV27800008 PM 7478765 ER PT J AU MERCHANT, SN NADOL, JB AF MERCHANT, SN NADOL, JB TI HISTOPATHOLOGY OF OSSICULAR IMPLANTS SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID EAR SURGERY; TRANSPLANTATION; RECONSTRUCTION; TYMPANOPLASTY; FATE C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114. HARVARD UNIV,CAMBRIDGE,MA 02138. FU NIDCD NIH HHS [DC0007928] NR 47 TC 19 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD AUG PY 1994 VL 27 IS 4 BP 813 EP 833 PG 21 WC Otorhinolaryngology SC Otorhinolaryngology GA PC575 UT WOS:A1994PC57500014 PM 7984378 ER PT J AU BLOCH, KJ AF BLOCH, KJ TI WHAT IS A CLINICAL IMMUNOLOGIST SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article C1 MASSACHUSETTS GEN HOSP,GEN MED SERV,ALLERGY UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP BLOCH, KJ (reprint author), MASSACHUSETTS GEN HOSP,GEN MED SERV,CLIN IMMUNOL UNIT,32 FRUIT ST,BULFINCH 422,BOSTON,MA 02114, USA. NR 9 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 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD AUG PY 1994 VL 41 IS 4 BP 591 EP 596 PG 6 WC Pediatrics SC Pediatrics GA PA771 UT WOS:A1994PA77100002 PM 8047363 ER PT J AU LIN, CW SHULOK, JR AF LIN, CW SHULOK, JR TI ENHANCEMENT OF NILE BLUE DERIVATIVE-INDUCED PHOTOCYTOTOXICITY BY NIGERICIN AND LOW CYTOPLASMIC PH SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Note ID MAMMALIAN-CELLS; PHOTODYNAMIC THERAPY; PHOTO-SENSITIZATION; IONOPHORE NIGERICIN; CYTO-TOXICITY; PHOTOSENSITIZERS; HEMATOPORPHYRIN; INVITRO; PHTHALOCYANINE; DESTRUCTION AB The mechanism of photocytotoxicity mediated by a lysosomotropic photosensitizer, Nile blue derivative (NBS-6I), in relation to lysosome destruction was examined by lowering the intracellular pH with low extracellular pH and an ionophore, nigericin. The treatment performed after photoirradiation had minimal effect on the cytotoxicity. However, when the treatment was initiated before photoirradiation, it caused a three orders of magnitude enhancement on cytotoxicity with a two orders of magnitude enhancement by nigericin alone. This effect on cytotoxicity resembles closely that observed on photosensitization mediated by chloroaluminum phthalocyanine. The enhancement in this case has been attributed to the synergistic interaction between photodamage and perturbation of ion transports across mitochondrial or plasma membranes by nigericin. Because these are not the main sites of localization for Nile blue photosensitizers nor their initial targets of photocytotoxic action, data from the present study suggest the possibility of an intracellular dye translocation induced by nigericin, which redistributes the Nile blue photosensitizer from lysosomes to other sites, as a possible cause of the enhancement of cytotoxicity. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP LIN, CW (reprint author), MASSACHUSETTS GEN HOSP,UROL RES LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA 32259] NR 32 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD AUG PY 1994 VL 60 IS 2 BP 143 EP 146 DI 10.1111/j.1751-1097.1994.tb05081.x PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PC467 UT WOS:A1994PC46700010 PM 7938211 ER PT J AU SAYRE, RM KOLLIAS, N LEY, RD BAQER, AH AF SAYRE, RM KOLLIAS, N LEY, RD BAQER, AH TI CHANGING THE RISK SPECTRUM OF INJURY AND THE PERFORMANCE OF SUNSCREEN PRODUCTS THROUGHOUT THE DAY SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE SUNLIGHT; RISK; SUN PROTECTION FACTOR; UVA; UVB; SUNSCREEN; PROTECTION ID PROTECTION; SKIN AB Sunscreen products are tested normally against a defined solar simulator spectrum that, in ultraviolet (UVB), closely resembles the noontime spectral composition of summer sunlight. Although such a spectrum may define the product for use in the most adverse sunlight conditions, little attention has been given to how such products perform against other natural sunlight spectra. Outdoor clinical trials suggest that indoor testing of sunscreens may overestimate the performance of many products. In this study we compared the predicted efficacy of specific products to a variety of natural sunlight spectra taken at different solar angles and under different atmospheric conditions. We found that a standard product always provides less protection for a natural sunlight spectrum than its label value would suggest. The deviation from the labeled value is the greatest when the sun is low in the sky, i.e., close to the horizon. The deviation is due to the changing ratio of UVA to UVB radiation in natural sunlight. The deviation can be as large as a factor of 2.0. C1 MASSACHUSETTS GEN HOSP,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. RAPID PRECIS TESTING LABS,CORDOVA,TN. AL SABAH HOSP,KUWAIT,KUWAIT. MEMPHIS STATE UNIV,DEPT PHYS,MEMPHIS,TN 38152. LOVELACE FDN MED EDUC & RES,ALBUQUERQUE,NM. NR 16 TC 14 Z9 14 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD AUG PY 1994 VL 10 IS 4 BP 148 EP 153 PG 6 WC Dermatology SC Dermatology GA PK467 UT WOS:A1994PK46700003 PM 7803225 ER PT J AU KIM, WS VACANTI, JP CIMA, L MOONEY, D UPTON, J PUELACHER, WC VACANTI, CA AF KIM, WS VACANTI, JP CIMA, L MOONEY, D UPTON, J PUELACHER, WC VACANTI, CA TI CARTILAGE ENGINEERED IN PREDETERMINED SHAPES EMPLOYING CELL TRANSPLANTATION ON SYNTHETIC BIODEGRADABLE POLYMERS SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB Cartilage is often used as structural support tissue for cosmetic repair in plastic and reconstructive surgery. We describe the efficacy of a new approach for the generation of cartilage in predetermined shapes using specially configured biodegradable synthetic polymer devices as delivery Vehicles for transplanted cells. Synthetic biodegradable polymer scaffolds were configured in one of four specific shapes, i.e., a triangle, a rectangle, a cross, and a cylinder. The polymer matrices were seeded with freshly isolated bovine articular chondrocytes and then implanted subcutaneously into nude mice. Gross examination of excised specimens 12 weeks after implantation revealed the presence of new hyaline cartilage of approximately the same dimensions as the original construct. This cartilage showed no signs of resorption or overgrowth over the 12-week time course of the experiment. Histologic evaluation using hematoxylin and eosin stains confirmed the presence of normal mature hyaline cartilage in 46 of 48 specimens. These results suggest that cartilage can be created in predetermined shapes and dimensions using cell transplantation on appropriate polymer templates. This technology would be useful in cosmetic and reconstructive surgery. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02173. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT SURG,BOSTON,MA. MIT,DEPT CHEM ENGN,CAMBRIDGE,MA 02139. NR 4 TC 141 Z9 155 U1 0 U2 7 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 AUG PY 1994 VL 94 IS 2 BP 233 EP 237 DI 10.1097/00006534-199408000-00001 PG 5 WC Surgery SC Surgery GA NZ789 UT WOS:A1994NZ78900001 PM 8041813 ER PT J AU CORRIGAN, PW GREEN, MF TOOMEY, R AF CORRIGAN, PW GREEN, MF TOOMEY, R TI COGNITIVE CORRELATES TO SOCIAL CUE PERCEPTION IN SCHIZOPHRENIA SO PSYCHIATRY RESEARCH LA English DT Article DE SOCIAL SKILLS TRAINING; REHABILITATION; INFORMATION PROCESSING; PSYCHIATRIC SYMPTOMS ID PREFRONTAL CORTEX; SKILLS; PERFORMANCE; DISORDER; MEMORY AB Previous research has examined social skill learning in schizophrenic patients in relation to information-processing deficits and psychiatric symptoms. Relationships were examined in the current report between social cue perception, thought to be an early and necessary component of skill learning, and various information-processing deficits and psychiatric symptoms. Twenty-six inpatients with DSM-III-R diagnoses of schizophrenia completed measures of social cue perception, cognitive functioning, and psychiatric symptoms. Results showed that cue perception was significantly related to measures of early visual processing, recognition memory, and psychiatric symptoms of withdrawal/retardation. Implications of these findings for future research into the social-perceptual deficits of schizophrenic patients are discussed. C1 UNIV CHICAGO,PRITZKER SCH MED,CHICAGO,IL 60637. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. BOSTON UNIV,BOSTON,MA 02215. VET ADM MED CTR,HARVARD UNIV,DEPT PSYCHIAT,BROCKTON,MA 02401. FU NIMH NIH HHS [MH-30911, MH-43292] NR 45 TC 59 Z9 59 U1 0 U2 5 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 AUG PY 1994 VL 53 IS 2 BP 141 EP 151 DI 10.1016/0165-1781(94)90105-8 PG 11 WC Psychiatry SC Psychiatry GA PJ157 UT WOS:A1994PJ15700004 PM 7824674 ER PT J AU GAZELLE, GS MUELLER, PR WARSHAW, AL AF GAZELLE, GS MUELLER, PR WARSHAW, AL TI COMMUNICATION BETWEEN THE MAIN PANCREATIC DUCT AND CYSTIC CAVITY IN PATIENTS WITH CYSTIC NEOPLASMS OF THE PANCREAS - RESPONSE SO RADIOLOGY LA English DT Letter RP GAZELLE, GS (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 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 AUG PY 1994 VL 192 IS 2 BP 583 EP 583 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NY349 UT WOS:A1994NY34900062 ER PT J AU SHIOTA, G KAWASAKI, H NAKAMURA, T SCHMIDT, EV AF SHIOTA, G KAWASAKI, H NAKAMURA, T SCHMIDT, EV TI ASSESSMENT OF IN-VITRO GROWTH-POTENTIAL OF HEPATOCYTES EXPRESSING HEPATOCYTE GROWTH-FACTOR IN AN AUTOCRINE FASHION SO RESEARCH COMMUNICATIONS IN MOLECULAR PATHOLOGY AND PHARMACOLOGY LA English DT Article ID CELLS; LIVER AB We recently developed transgenic mice expressing hepatocyte growth factor (HGF) specific to hepatocytes. Hepatocytes of HGF transgenic mice showed a 2-fold increase of DNA labeling indices in vivo compared with those of wild type mice. To assess in vitro growth potential of hepatocytes from HGF transgenic mice, we studied the effects of epidermal growth factor (EGF), insulin or transforming growth factor beta (TGF beta) on DNA synthesis of hepatocytes derived from HGF transgenic or wild type mice, respectively. We found that DNA synthesis of hepatocytes from HGF transgenic mice was significantly enhanced, compared with that from wild type mice, respectively, and that its effect was additive with EGF or insulin. Further, growth-inhibitory effects of TGF beta on hepatocytes was greatly depressed in transgenic mice-derived hepatocytes, compared with that in wild type hepatocytes. These data suggest that the autocrine action of HGF is a potent stimulus for hepatocyte growth, and stress its importance as regulator of liver regeneration. C1 OSAKA UNIV,BIOMED RES CTR,DIV TUMOR BIOCHEM,SUITA,OSAKA 565,JAPAN. MASSACHUETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. RP SHIOTA, G (reprint author), TOTTORI UNIV,SCH MED,DEPT INTERNAL MED 2,YONAGO,TOTTORI 683,JAPAN. NR 9 TC 1 Z9 1 U1 0 U2 0 PU P J D PUBLICATIONS LTD PI WESTBURY PA PO BOX 966, WESTBURY, NY 11590 SN 1078-0297 J9 RES COMMUN MOL PATH JI Res. Commun. Mol. Pathol. Pharmacol. PD AUG PY 1994 VL 85 IS 2 BP 151 EP 156 PG 6 WC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pathology; Pharmacology & Pharmacy GA PG787 UT WOS:A1994PG78700004 PM 7994559 ER PT J AU ORWOLL, ES BLIZIOTES, M AF ORWOLL, ES BLIZIOTES, M TI HETEROGENEITY IN OSTEOPOROSIS - MEN VERSUS WOMEN SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID BONE-MINERAL DENSITY; AGE-RELATED-CHANGES; CORTICOSTEROID-INDUCED OSTEOPOROSIS; RADIAL PHOTON-ABSORPTIOMETRY; HIP FRACTURE INCIDENCE; SEX-RELATED CHANGES; TRABECULAR BONE; SPINAL OSTEOPOROSIS; DIETARY CALCIUM; HEALTHY-MEN C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. RP ORWOLL, ES (reprint author), PORTLAND VET AFFAIRS MED CTR,BONE & MINERAL RES UNIT,3710 SW US VET HOSP RD,PORTLAND,OR 97201, USA. OI Orwoll, Eric/0000-0002-8520-7355 NR 141 TC 15 Z9 15 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD AUG PY 1994 VL 20 IS 3 BP 671 EP 689 PG 19 WC Rheumatology SC Rheumatology GA PC560 UT WOS:A1994PC56000009 PM 7984784 ER PT J AU KIMMEL, DB SLOVIK, DM LANE, NE AF KIMMEL, DB SLOVIK, DM LANE, NE TI CURRENT AND INVESTIGATIONAL APPROACHES FOR REVERSING ESTABLISHED OSTEOPOROSIS SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID POSTMENOPAUSAL BONE LOSS; GROWTH-FACTOR-I; INTERLEUKIN-1 RECEPTOR ANTAGONIST; PARATHYROID-HORMONE 1-38; CONGENITAL HEART-DISEASE; METAPHYSEAL HARD TISSUE; OSTEOPENIC OVARIECTOMIZED RATS; ESTROGEN REPLACEMENT THERAPY; CONTROLLED-RELEASE PELLETS; VERTEBRAL FRACTURE RATE C1 SPAULDING REHABIL HOSP,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. SAN FRANCISCO GEN HOSP,MED CTR,SAN FRANCISCO,CA 94110. RP KIMMEL, DB (reprint author), CREIGHTON UNIV,SCH MED,CTR OSTEOPOROSIS RES,601 N 30TH ST 5766,OMAHA,NE 68131, USA. NR 263 TC 19 Z9 20 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD AUG PY 1994 VL 20 IS 3 BP 735 EP 758 PG 24 WC Rheumatology SC Rheumatology GA PC560 UT WOS:A1994PC56000012 PM 7984787 ER PT J AU CATALANO, P RYAN, L SCHARFSTEIN, D AF CATALANO, P RYAN, L SCHARFSTEIN, D TI MODELING FETAL DEATH AND MALFORMATION IN DEVELOPMENTAL TOXICITY STUDIES SO RISK ANALYSIS LA English DT Article DE BENCHMARK DOSE; BINARY DATA; DEVELOPMENTAL TOXICITY; DOSE RESPONSE MODELING; RISK ASSESSMENT ID QUANTITATIVE RISK ASSESSMENT; LONGITUDINAL DATA-ANALYSIS; GLYCOL DIMETHYL ETHER; CONTINUOUS OUTCOMES; MICE; TERATOLOGY; DISCRETE; WEIGHT; RATS AB We review approaches to dose-response modeling and risk assessment for binary data from developmental toxicity studies. In particular, we focus on jointly modeling fetal death and malformation and use a continuation ratio formulation of the multinomial distribution to provide a model for risk. Generalized estimating equations are used to account for clustering of animals within litters. The fitted model is then used to calculate doses corresponding to a specified level of excess risk. Two methods of arriving at a lower confidence limit or Benchmark dose are illustrated and compared. We also discuss models based on single binary end points and compare our approach to a binary analysis of whether or not the animal was 'affected' (either dead or malformed). The models are illustrated using data from four developmental toxicity studies in EG, DEHP, TGDM, and DYME conducted through the National Toxicology Program. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP CATALANO, P (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115, USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 27 TC 9 Z9 9 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD AUG PY 1994 VL 14 IS 4 BP 629 EP 637 DI 10.1111/j.1539-6924.1994.tb00276.x PG 9 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA PK031 UT WOS:A1994PK03100022 PM 7972963 ER PT J AU KERSTEN, CM MCCLUSKEY, RT WARREN, HS KURNICK, JT AF KERSTEN, CM MCCLUSKEY, RT WARREN, HS KURNICK, JT TI RESPONSES OF HUMAN T-CELLS TO DOMINANT DISCRETE PROTEIN ANTIGENS OF ESCHERICHIA-COLI AND PSEUDOMONAS-AERUGINOSA SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID MACROPHAGES AB Normal human beings have circulating T lymphocytes that proliferate in response to Escherichia coli and Pseudomonas aeruginosa. We performed the present study to characterize the nature of the responding T cells and to determine whether distinct or shared conventional antigens, superantigens or polylonal activators account for T cell proliferation. Long term antigen-specific T cell lines were generated by repeated stimulation of PBMC from four donors with soluble antigen preparations of E. coli or P. aeruginosa. This resulted in the emergence of distinct T cell populations, which responded to strains of either E. coli or P. aeruginosa, but not to both. Trypsin treatment of the bacterial preparations largely eliminated their ability to stimulate the T cells. The T cell lines were predominantly CD4(+) and their proliferation to bacterial antigens was optimal using autologous APC. E. coli T cell lines proliferated not only in response to the E. coli strain with which they were initially selected, but also to four different strains of E. coli, as well as to several related Gram-negative species. P. aeruginosa selected T cells exhibited proliferative responses to six different P. aeruginosa strains, but not to the other Gram-negative species. The finding that repeated stimulation of PBMC with E. coli or P. aeruginosa leads to CD4(+) T cells highly reactive with conventional protein antigens specific either for E. coli or P. aeruginosa indicates that these bacteria possess separate dominant protein antigens that drive the proliferation of peripheral blood T cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,BOSTON,MA. FU NHLBI NIH HHS [HL-43793]; NIAID NIH HHS [R29AI-28943-04] NR 23 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD AUG PY 1994 VL 40 IS 2 BP 151 EP 157 DI 10.1111/j.1365-3083.1994.tb03444.x PG 7 WC Immunology SC Immunology GA NZ204 UT WOS:A1994NZ20400004 PM 7519358 ER PT J AU BRIDGES, AJ AF BRIDGES, AJ TI AUTOANTIBODIES IN PATIENTS WITH SILICONE IMPLANTS SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Article; Proceedings Paper CT Symposium on Silicone-Related Disorders CY DEC 04, 1992 CL WASHINGTON, DC SP GEORGE WASHINGTON UNIV MED CTR DE SILICONE; AUTOANTIBODIES; CENTROMERE; RIBONUCLEOPROTEINS ID CONNECTIVE-TISSUE DISEASE; HUMAN ADJUVANT DISEASE; PROGRESSIVE SYSTEMIC-SCLEROSIS; GEL BREAST IMPLANTS; AUGMENTATION MAMMOPLASTY; ANTINUCLEAR ANTIBODIES; AUTOIMMUNE-DISEASES; LUPUS-ERYTHEMATOSUS; CHRONIC ARTHROPATHY; RHEUMATIC DISEASE C1 UNIV WISCONSIN,DEPT MED,RHEUMATOL SECT,MADISON,WI 53706. MIDDLETON VET ADM HOSP,MADISON,WI. NR 34 TC 18 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD AUG PY 1994 VL 24 IS 1 SU 1 BP 54 EP 60 DI 10.1016/0049-0172(94)90110-4 PG 7 WC Rheumatology SC Rheumatology GA PC954 UT WOS:A1994PC95400009 PM 7801140 ER PT J AU ELIAS, AD AF ELIAS, AD TI SALVAGE THERAPY FOR SOFT-TISSUE SARCOMAS SO SEMINARS IN ONCOLOGY LA English DT Article; Proceedings Paper CT Cleveland Clinic Foundation CME Program on the Community Approach to Salvage Therapy in the Treatment of Advanced Cancer CY JUN 18-19, 1993 CL CLEVELAND, OH SP CLEVELAND CLIN ID ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; UNRESECTABLE SARCOMA; SURGICAL RESECTION; PHASE-II; IFOSFAMIDE; DOXORUBICIN; ADRIAMYCIN; DACARBAZINE; MESNA RP ELIAS, AD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 36 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 1994 VL 21 IS 4 SU 7 BP 76 EP 81 PG 6 WC Oncology SC Oncology GA PJ824 UT WOS:A1994PJ82400012 PM 8091245 ER PT J AU SARANTOS, P ABOUHAMZE, A ABCOUWER, S CHAKRABARTI, R COPELAND, EM SOUBA, WW AF SARANTOS, P ABOUHAMZE, A ABCOUWER, S CHAKRABARTI, R COPELAND, EM SOUBA, WW TI CYTOKINES DECREASE GLUTAMINASE EXPRESSION IN HUMAN FIBROBLASTS SO SURGERY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-12, 1994 CL JACKSON, MS SP SOC UNIV SURGEONS ID TUMOR-NECROSIS-FACTOR; CULTURED HUMAN-FIBROBLASTS; HUMAN DIPLOID FIBROBLASTS; TNF-ALPHA; TRANSPORT; GLUCOSE; CELLS AB Background. Glutamine metabolism in fibroblasts is essential for energy production, nucleotide biosynthesis, and growth during wound healing. Because cytokines can impair fibroblast proliferation, we tested the hypothesis that cytokines impair glutamine metabolism. We studied the influence of several cytokines on the expression of glutaminase, the major enzyme of intracellular glutamine metabolism in fibroblasts. Methods. Human foreskin fibroblasts were incubated for 6 and 12 hours with varying doses (10, 100, or 1000 units/ml) of interleukin (IL)-1, IL-6, tumor necrosis factor-alpha, or gamma-interferon. Cell lysates were assayed for glutaminase-specific activity, and glutaminase protein content was measured by Western blotting with a polyclonal antibody. Total cellular RNA was extracted, and relative glutaminase messenger RNA levels were determined by Northern blotting with a P-32-labeled glutaminase complement DNA-derived probe. These mRNA levels were normalized by blotting with a beta-actin cDNA-derived probe as control. Cell nuclei were isolated, and nuclear run-ons were used to determine relative glutaminase mRNA transcription rates. Results. IL-1, IL-6, tumor necrosis factor-alpha, and gamma-interferon decreased glutaminase activity and protein concentration after a 12-hour incubation in a dose-independent fashion. No difference was noted at 6 hours. Western blot analysis showed a 30% to 60% reduction in glutaminase protein zn treated cells. These cytokines also decreased glutaminase mRNA levels, consistent with transcriptional regulation. This was confirmed by nuclear run-an assays that showed a decrease in the number of glutaminase transcripts. Conclusions. A variety of different pro-inflammatory cytokines decrease glutaminase expression In cultured human fibroblasts. This cytokine-mediated inhibition of glutamine metabolism may limit the availability of key glutamine-derived intermediates and impair fibroblast proliferation in certain patients. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. UNIV FLORIDA,COLL MED,DEPT SURG,GAINESVILLE,FL. HARVARD UNIV,SCH MED,BOSTON,MA. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NCI NIH HHS [CA 45327] NR 23 TC 13 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1994 VL 116 IS 2 BP 276 EP 284 PG 9 WC Surgery SC Surgery GA PA544 UT WOS:A1994PA54400022 PM 7519362 ER PT J AU INOUE, Y BODE, BP SOUBA, WW AF INOUE, Y BODE, BP SOUBA, WW TI ANTIBODY TO TUMOR-NECROSIS-FACTOR ATTENUATES ENDOTOXIN-STIMULATED AMINO-ACID-TRANSPORT IN RAT-LIVER SO SURGERY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-12, 1994 CL JACKSON, MS SP SOC UNIV SURGEONS ID PLASMA-MEMBRANE VESICLES; SYSTEM; METABOLISM; GLUTAMINE; CELL AB Background. Endotoxemia stimulates amino acid consumption by the liver, but the regulation of this response is poorly understood. We studied the effect of Escherichia coli endotoxin role of the cytokine tumor necrosis factor-alpha (TNF) in regulating this transport activity. Methods. We investigated the activities of the Na+-dependent amino acid transport systems A, ASC, and N in hepatic plasma membrane vesicles prepared from rats treated with endotoxin in vivo. Vesicle purity and functionality were evaluated by assaying marker enzymes and by the presence of classic overshoots. Results. Endotoxin treatment did not alter sodium transport but resulted in time- and dose-dependent 6-fold (system A), 3.5-fold (system N), and 3-fold (system ASC) increases in transport activity secondary to an increase in carrier maximum velocity. Lipopolysaccharide treatment did not alter transporter affinity or plasma membrane sodium transport. Transport activity increased within 2 hours of endotoxin administration, peaked at 4 hours after exposure to lipopolysaccharide, and returned to basal levels within 24 hours. Pretreatment of animals with an anti-TNF monoclonal antibody diminished the endotoxin-induced enhancement in transport activity by 50% to 75% by decreasing carrier maximum velocity. In contrast, when the antibody was given after endotoxin challenge, transport activity was not attenuated. Conclusions. The marked acceleration in hepatic amino acid uptake that occurs during endotoxemia is secondary to an increased Na+-dependent hepatocyte plasma membrane transport activity and is mediated, in large part by the cytokine TNF. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV FLORIDA,COLL MED,DEPT SURG,GAINESVILLE,FL. FU NCI NIH HHS [CA 45327] NR 25 TC 18 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1994 VL 116 IS 2 BP 356 EP 366 PG 11 WC Surgery SC Surgery GA PA544 UT WOS:A1994PA54400032 PM 8048001 ER PT J AU BURKE, PA CANNING, CM CHARTIER, S LAZO, S DALEY, J FORSE, RA RITZ, J AF BURKE, PA CANNING, CM CHARTIER, S LAZO, S DALEY, J FORSE, RA RITZ, J TI ALTERATIONS IN CA2+ SIGNAL-TRANSDUCTION IN CRITICALLY ILL SURGICAL PATIENTS SO SURGERY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Society-of-University-Surgeons CY FEB 09-12, 1994 CL JACKSON, MS SP SOC UNIV SURGEONS ID METHIONYL-LEUCYL-PHENYLALANINE; INTRACELLULAR FREE CALCIUM; HUMAN-NEUTROPHILS; TRAUMA PEPTIDE; LIPOPOLYSACCHARIDE; RECEPTOR; SEPSIS; BURST; CELLS; LPS AB related disorders such as systemic inflammatory response syndrome (SIRS) continue to be a setting may in part be mediated at the level of early signal transduction in monocytes and neutrophils as manifested by changes in intracellular free Ca2+. Methods. Monocytes and neutrophils were isolated from patients in the intensive care unit who met the criteria for SIPS and from normal volunteers. Cells were loaded with the Ca2+-sensitive fluorescent dye Indo-1 and stimulated with the chemotactic peptide S-Met-Leu-Phe (fMLP). Changes in intracellular calcium ion concentration were measured by flow cytometry. Results. Patient monocytes exhibited a decreased Ca2+ flux (43% +/- 3.1%) as compared with normal monocytes (63% +/- 2.5%) (p < 0.05). Patient neutrophils also exhibited a decreased Ca2+ flux in response to fMLP of 58% +/- 3.7% versus 69.3% +/- 3.1% Sor normal neutrophils (p < 0.05). Incubation of patient cells in normal plasma reversed this dysfunction and showed an improved Ca2+ flux to 60% +/- 2.7% for monocytes and 71% +/- 3.7% Sor neutrophils (p < 0.05). Conversely, calcium flux was decreased in both normal monocytes (42.3% +/- 3.1%) and normal neutrophils (55.4% +/- 3.8%) after incubation in SIPS patient plasma (p < 0.05). Incubation of normal fMLP. Conclusions. Patients with SIRS exhibit alterations in early signal transduction after stimulation with fMLP in monocytes and neutrophils. This effect appears to be mediated by a soluble factor because the defect in SIRS patient cells can be reversed by incubation in normal plasma and normal cells appear to acquire this defect after incubation in patient plasma. Further studies are underway to identify the factor or factors responsible Sor this functional defect. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. RP BURKE, PA (reprint author), NEW ENGLAND DEACONESS HOSP,DEPT SURG,110 FRANCIS ST,8C,BOSTON,MA 02115, USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1994 VL 116 IS 2 BP 378 EP 387 PG 10 WC Surgery SC Surgery GA PA544 UT WOS:A1994PA54400034 PM 8048003 ER PT J AU DAWSON, SL MUELLER, PR AF DAWSON, SL MUELLER, PR TI INTERVENTIONAL RADIOLOGY IN THE MANAGEMENT OF BILE-DUCT INJURIES SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID LAPAROSCOPIC CHOLECYSTECTOMY; COMPLICATIONS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP DAWSON, SL (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. NR 11 TC 24 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 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD AUG PY 1994 VL 74 IS 4 BP 865 EP 874 PG 10 WC Surgery SC Surgery GA PB208 UT WOS:A1994PB20800012 PM 8047946 ER PT J AU GRABOWSKI, EF AF GRABOWSKI, EF TI GUIDELINES FOR THE HEMATOLOGIC EVALUATION OF CONTRAST-MEDIA - FOR THE SUBCOMMITTEE ON RHEOLOGY, BIOMATERIALS, AND CONTACT ACTIVATION OF THE SCIENTIFIC AND STANDARDIZATION COMMITTEE OF THE INTERNATIONAL SOCIETY ON THROMBOSIS AND HEMOSTASIS SO THROMBOSIS AND HAEMOSTASIS LA English DT Note ID MECHANISMS; INHIBITION; AGENTS; BLOOD RP GRABOWSKI, EF (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WANG AMBULATORY CARE CTR,PEDIAT HEMATOL ONCOL UNI,BOSTON,MA 02114, USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD AUG PY 1994 VL 72 IS 2 BP 322 EP 324 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA PC407 UT WOS:A1994PC40700028 PM 7831672 ER PT J AU APITZCASTRO, R BADIMON, JJ BADIMON, L AF APITZCASTRO, R BADIMON, JJ BADIMON, L TI A GARLIC DERIVATIVE, AJOENE, INHIBITS PLATELET DEPOSITION ON SEVERELY DAMAGED VESSEL WALL IN AN IN-VIVO PORCINE EXPERIMENTAL-MODEL SO THROMBOSIS RESEARCH LA English DT Article DE AJOENE; THROMBUS FORMATION; VESSEL WALL; PLATELETS ID VIII-VONWILLEBRAND FACTOR; GLYCOPROTEIN IIB-IIIA; COLLAGEN TYPE-I; ANTIPLATELET COMPOUND; THROMBUS FORMATION; SHEAR RATE; ARTERY SUBENDOTHELIUM; ADHESION; BLOOD; EXVIVO AB Ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, is a potent antiplatelet compound isolated from alcoholic extracts of garlic. In vitro ajoene reversibly inhibits platelet aggregation as well as the release reaction induced by all known agonists. We used a well characterized perfusion chamber to study the in vivo effects of ajoene on platelet deposition onto a highly thrombogenic, severely damaged arterial wall, obtained by stripping off the intimal layer and exposing tunica media. Platelet-vessel wall interaction and the effect of ajoene was studied under flow conditions of high and low local shear rate that mimics laminar blood flow in small and medium size arteries (1690 sec(-1) and 212 sec(-1)). Our results indicate that administration of ajoene to heparinized animals, significantly prevents thrombus formation at local low blood shear rate. Ajoene does not inhibit binding of vWF to GPIb, therefore, it does not affect platelet adhesion. In fact, although ajoene impairs fibrinogen and vWF (less efficient) binding to GPlIb/IIIa, it does not totally inhibits platelet deposition to the substrates at any of the shear rates used in this study. Our present results, under in vivo flow conditions and in the presence of physiological calcium levels, suggest that ajoene may be potentially useful for the acute prevention of thrombus formation induced by severe vascular damage, mainly in arterial sites with local low shear rates. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA. INST VENEZOLANO INVEST CIENT,TROMBOSIS EXPTL LAB,CARACAS 1020A,VENEZUELA. CID HOSP ST PAU,CARDIOVASC RES UNIT & FDN,BARCELONA,SPAIN. RI BADIMON, LINA/O-4711-2014 OI BADIMON, LINA/0000-0002-9162-2459 FU NHLBI NIH HHS [HL-38393] NR 19 TC 35 Z9 37 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD AUG 1 PY 1994 VL 75 IS 3 BP 243 EP 249 DI 10.1016/0049-3848(94)90235-6 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA NX882 UT WOS:A1994NX88200003 PM 7992235 ER PT J AU KAWAI, T WONG, J MACLEAN, J COSIMI, AB WEE, SL AF KAWAI, T WONG, J MACLEAN, J COSIMI, AB WEE, SL TI CHARACTERIZATION OF A MONOCLONAL-ANTIBODY (6G12) RECOGNIZING THE CYNOMOLGUS MONKEY CD3 ANTIGEN SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 3rd Congress of the Asian-Society-of-Transplantation CY DEC 04-06, 1993 CL BANGKOK, THAILAND SP ASIAN SOC TRANSPLANTAT, THAI TRANSPLANTAT SOC, KIDNEY FDN THAILAND, MINIST PUBLIC HLTH, THAILAND, ROYAL COLL SURGEONS THAILAND, ROYAL COLL PHYSICIANS THAILAND, SOC THORAC SURGEONS THAILAND, HEART ASSOC THAILAND, ASSOC UROLOG SURGEONS THAILAND, GASTROENTEROL ASSOC THAILAND, NEPHROL SOC THAILAND, ROYAL COLL ANESTHESIOLOGISTS THAILAND ID RENAL-ALLOGRAFT RECIPIENTS C1 MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANTAT UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,IMMUNOPATHOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NHLBI NIH HHS [HL-18646]; NIAID NIH HHS [R21 AI037692, R21 AI037692-06] NR 5 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1994 VL 26 IS 4 BP 1845 EP 1846 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PB867 UT WOS:A1994PB86700001 PM 8066600 ER PT J AU COSIMI, AB AF COSIMI, AB TI PROGRESS IN MONOCLONAL-ANTIBODIES IN CLINICAL TRANSPLANTATION SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 3rd Congress of the Asian-Society-of-Transplantation CY DEC 04-06, 1993 CL BANGKOK, THAILAND SP ASIAN SOC TRANSPLANTAT, THAI TRANSPLANTAT SOC, KIDNEY FDN THAILAND, MINIST PUBLIC HLTH, THAILAND, ROYAL COLL SURGEONS THAILAND, ROYAL COLL PHYSICIANS THAILAND, SOC THORAC SURGEONS THAILAND, HEART ASSOC THAILAND, ASSOC UROLOG SURGEONS THAILAND, GASTROENTEROL ASSOC THAILAND, NEPHROL SOC THAILAND, ROYAL COLL ANESTHESIOLOGISTS THAILAND ID RANDOMIZED CONTROLLED TRIAL; RENAL-ALLOGRAFT RECIPIENTS; LIVER-TRANSPLANTATION; IMMUNOSUPPRESSION; REJECTION; OKT3 C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. RP COSIMI, AB (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,TRANSPLANT UNIT,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-18646] NR 14 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 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1994 VL 26 IS 4 BP 1943 EP 1944 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA PB867 UT WOS:A1994PB86700043 PM 7915057 ER PT J AU POWELL, SN MCMILLAN, TJ AF POWELL, SN MCMILLAN, TJ TI THE REPAIR FIDELITY OF RESTRICTION ENZYME-INDUCED DOUBLE-STRAND BREAKS IN PLASMID DNA CORRELATES WITH RADIORESISTANCE IN HUMAN TUMOR-CELL LINES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE DNA REPAIR; RADIATION RESISTANCE; MISREPAIR; PLASMID; RESTRICTION ENDONUCLEASES; HUMAN TUMOR CELL LINES ID HUMAN BLADDER-CARCINOMA; RADIATION-SENSITIVE CLONE; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; MAMMALIAN-CELLS; RADIOSENSITIVITY; MUTATION; INDUCTION; RESISTANCE; DEFECT AB Purpose: The accuracy of DNA repair may play a role in determining the cytotoxic effect of ionizing radiation. Repair, as measured by DNA strand breakage, often shows little difference between tumor cell lines of widely different radiosensitivity. The mechanism by which DNA fragments are rejoined is poorly understood. This study used plasmid transfection as a probe to assess the balance between correct repair and misrepair. Methods and Materials: Using techniques described, a double-strand break was introduced into a coding sequence of circular plasmid DNA using a restriction endonuclease as a model for a radiation-induced double-strand break; it was then transfected as a linear molecule into human tumor cells, and the subsequent cell-mediated restoration of the coding sequence, evidenced by intact gene function, was documented. The plasmid used in these experiments, pPMH16, is known to integrate into genomic DNA. Gene function was tested by the ability to grow colonies in selection media. The plasmid also contains a second selectable marker gene that was used to identify transfected cells, before the function of the damaged gene was tested. The proportion of transfected cells that had correctly restored the damaged gene gave a measure of repair fidelity. Results: A general trend for sensitive cells to show lower repair fidelity relative to resistant cells was observed. The type of double-strand cleavage of the plasmid (staggered or blunt) made little difference to the measured repair fidelity, in contrast to published studies in which restriction-enzyme breaks had been introduced into DNA within chromatin. Specific comparison of parent lines and their radiosensitive clones showed significant differences in repair fidelity for a relatively small change in radiation response, which was in line with the overall correlation. These same pairs have previously been shown to have no difference in the loss of DNA fragmentation with time after irradiation, and Southern analysis had confirmed the integrated plasmid copy number was similar in the cell lines compared. The number of intact copies of the damaged gene relative to the undamaged gene mirrored the observed repair fidelity. However, in one cell line out of the 10 studied, an exception to the observed trend was found. In a comparison of two equally radioresistant bladder cancer cell lines, large differences in repair fidelity were observed. Again, no difference in the integrated copy number was found, and the damaged gene was highly rearranged or deleted in the cell line with low repair fidelity. Conclusion: These studies have shown repair fidelity to correlate closely with radiosensitivity, including the comparison of genetically related lines. It is suggested that repair fidelity can be, but is not invariably, a measure of correct repair relative to misrepair, resulting from the processing of double-strand breaks and, hence, the response to ionizing radiation. C1 INST CANC RES,RADIAT RES UNIT,SUTTON,SURREY,ENGLAND. RP POWELL, SN (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 24 TC 45 Z9 45 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 30 PY 1994 VL 29 IS 5 BP 1035 EP 1040 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA PE338 UT WOS:A1994PE33800014 PM 8083072 ER PT J AU DIGNASS, AU LYNCHDEVANEY, K PODOLSKY, DK AF DIGNASS, AU LYNCHDEVANEY, K PODOLSKY, DK TI HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR MODULATES INTESTINAL EPITHELIAL-CELL PROLIFERATION AND MIGRATION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID SCATTER FACTOR; FACTOR-BETA; EXPRESSION; RECEPTOR; TISSUES; LINE AB Various peptide growth factors have been found to regulate epithelial cell function within the mucosal epithelium of the gastrointestinal tract. In this study hepatocyte growth factor/scatter factor (HGF/SF) was found to stimulate intestinal epithelial cell proliferation: 2.5-fold in the non-transformed rat small intestinal epithelial cell line IEC-6 and 1.9-fold in the human colon cancer-derived HT-29 cell line. In addition, HGF/SF enhanced epithelial cell restitution, the initial step involved in gastrointestinal wound healing, in an in vitro model. Migration of IEC-6 in wounded monolayers was enhanced up to 7-fold. Enhancement of restitution by HGF could be completely abrogated by addition of immunoneutralizing anti-TGF beta 1, indicating that this process is mediated through a TGF beta-dependent pathway. These findings suggest that HGF exerts functional effects on intestinal epithelial cell populations and may play a role in the morphogenesis tract and its remodeling following injury. (C) 1994 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [DK-41557, DK-43351] NR 26 TC 131 Z9 133 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 29 PY 1994 VL 202 IS 2 BP 701 EP 709 DI 10.1006/bbrc.1994.1987 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NZ240 UT WOS:A1994NZ24000009 PM 8048940 ER PT J AU PEDRINI, MT GIORGINO, F SMITH, RJ AF PEDRINI, MT GIORGINO, F SMITH, RJ TI CDNA CLONING OF THE RAT IGF-I RECEPTOR - STRUCTURAL-ANALYSIS OF RAT AND HUMAN IGF-I AND INSULIN-RECEPTORS REVEALS DIFFERENCES IN ALTERNATIVE SPLICING AND RECEPTOR-SPECIFIC DOMAIN CONSERVATION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GROWTH FACTOR-I; MESSENGER-RNA; GENE; EXPRESSION; METABOLISM; GLUCOSE; REGION; CELLS AB IGF I and insulin receptors are homologous proteins that function in distinct physiological pathways. To define domains that might contribute to differences between IGF I and insulin receptors, we cloned the rat IGF I receptor cDNA and performed a comparative sequence analysis of specific functional domains in the two receptor types of rats and humans. Since alternative splicing has been shown to alter the activities of both IGF I and insulin receptors, we also examined the mRNA splicing patterns of the two receptors. The C-terminal region exhibits the lowest degree of amino acid homology between rat and human IGF I receptors (85%) and the tyrosine kinase domain the highest homology (98%). In the region corresponding to the CAG+/- alternative splicing site of the human IGF I receptor, a nucleotide change in the rat eliminates the alternative acceptor splice site. The rat IGF I receptor has no equivalent to the alternatively spliced exon 11 of the insulin receptor. The IGF I and insulin receptors are highly homologous in the tyrosine kinase domain (84%), but differ markedly in other specific regions (e.g., 22-26% homology in the transmembrane domain, 45% homology in the C-terminal domain). We speculate that these regions of divergent sequence may have roles in determining distinct signaling properties of IGF I and insulin receptors. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,BOSTON,MA 02215. RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 FU NIDDK NIH HHS [DK36836, DK43038]; NIGMS NIH HHS [GM36428] NR 25 TC 20 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 29 PY 1994 VL 202 IS 2 BP 1038 EP 1046 DI 10.1006/bbrc.1994.2033 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NZ240 UT WOS:A1994NZ24000055 PM 8048916 ER PT J AU MIRZABEKOV, T LIN, MC YUAN, WL MARSHALL, PJ CARMAN, M TOMASELLI, K LIEBERBURG, I KAGAN, BL AF MIRZABEKOV, T LIN, MC YUAN, WL MARSHALL, PJ CARMAN, M TOMASELLI, K LIEBERBURG, I KAGAN, BL TI CHANNEL FORMATION IN PLANAR LIPID BILAYERS BY A NEUROTOXIC FRAGMENT OF THE BETA-AMYLOID PEPTIDE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ALZHEIMERS-DISEASE; PROTEIN; PRECURSOR; MEMBRANES; AGGREGATION; NEURONS AB Alzheimer's disease (AD) pathology is characterized by plaques, tangles, and neuronal cell loss. The main constituent of plaques is beta-amyloid peptide (A beta), a 39-42 residue peptide which has been linked to disruption of calcium homeostasis and neurotoxicity in vitro. We demonstrate that a neurotoxic fragment of A beta, A beta (25-35) spontaneously inserted into planar lipid membranes to form weakly selective, voltage dependent, ion-permeable channels. We suggest that channel formation may be involved in the pathogenesis of AD and that A beta (25-35) may be the active channel forming segment. (C) 1994 Academic Press, Inc C1 UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90024. ATHENA NEUROSCI INC,S SAN FRANCISCO,CA 94080. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. FU NIMH NIH HHS [NIMH MH01174, NIMH MH443433] NR 25 TC 97 Z9 104 U1 0 U2 4 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 JUL 29 PY 1994 VL 202 IS 2 BP 1142 EP 1148 DI 10.1006/bbrc.1994.2047 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NZ240 UT WOS:A1994NZ24000069 PM 7519420 ER PT J AU WANG, TW DONAHOE, PK ZERVOS, AS AF WANG, TW DONAHOE, PK ZERVOS, AS TI SPECIFIC INTERACTION OF TYPE-I RECEPTORS OF THE TGF-BETA FAMILY WITH THE IMMUNOPHILIN FKBP-12 SO SCIENCE LA English DT Article ID TRANSMEMBRANE SERINE KINASE; GROWTH-FACTOR-BETA; PROTEIN-KINASE; THREONINE KINASE; ACTIVIN; COMPLEX; EXPRESSION; CLONING AB Transforming growth factor-beta (TGF-beta) family members bind to receptors that consist of heteromeric serine-threonine kinase subunits (type I and type II). In a yeast genetic screen, the immunophilin FKBP-12, a target of the macrolides FK506 and rapamycin, interacted with the type I receptor for TGF-beta and with other type I receptors. Deletion, point mutation, and co-immunoprecipitation studies further demonstrated the specificity of the interaction. Excess FK506 competed with type I receptors for binding to FKBP-12, which suggests that these receptors share or overlap the macrolide binding site on FKBP-12, and therefore they may represent its natural ligand. The specific interaction between the type I receptors and FKBP-12 suggests that FKBP-12 may play a role in type I receptor-mediated signaling. C1 MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114. FU NCI NIH HHS [CA17393]; NICHD NIH HHS [NICHD P-32 HD07396, NICHD P-30 HD28138] NR 21 TC 287 Z9 299 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 29 PY 1994 VL 265 IS 5172 BP 674 EP 676 DI 10.1126/science.7518616 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NZ538 UT WOS:A1994NZ53800037 PM 7518616 ER PT J AU CALLAHAN, TL HALL, JE ETTNER, SL CHRISTIANSEN, CL GREENE, MF CROWLEY, WF AF CALLAHAN, TL HALL, JE ETTNER, SL CHRISTIANSEN, CL GREENE, MF CROWLEY, WF TI THE ECONOMIC-IMPACT OF MULTIPLE-GESTATION PREGNANCIES AND THE CONTRIBUTION OF ASSISTED-REPRODUCTION TECHNIQUES TO THEIR INCIDENCE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INVITRO FERTILIZATION; INTRAFALLOPIAN TRANSFER; INFANT-MORTALITY; UNITED-STATES; BIRTH-WEIGHT; MANAGEMENT; PREVENTION; OVULATION; TRIPLETS; TWINS AB Background. Although the medical complications associated with multiple-gestation pregnancies have been well documented, little is known about the effects of such pregnancies on the use of health care resources and the associated costs. This is an important issue because of the increasing use of assisted-reproduction techniques, which commonly result in multiple-gestation pregnancies. Methods. We determined hospital charges and the use of assisted-reproduction techniques (such as induction of ovulation, in vitro fertilization, and gamete intrafallopian transfer) for 13,206 pregnant women (11,986 with singleton pregnancies, 1135 with twin pregnancies, and 85 with more than two fetuses) who were admitted for delivery to Brigham and Women's Hospital, Boston, in 1986 through 1991 and their 14,033 neonates (11,671 singletons, 2144 twins, and 218 resulting from higher-order multiple gestations). Results. After we controlled for variables known to affect hospital charges, the predicted total charges to the family in 1991 for a singleton delivery were $9,845, as compared with $37,947 for twins ($18,974 per baby) and $109,765 for triplets ($36,588 per baby). Assisted-reproduction techniques were used in 2 percent of singleton, 35 percent of twin, and 77 percent of higher-order multiple-gestation pregnancies; such procedures were approximately equally divided between induction of ovulation alone and in vitro fertilization or gamete intrafallopian transfer. Conclusions. Multiple-gestation pregnancies, a high proportion of which result from the use of assisted-reproduction techniques, dramatically increase hospital charges. If all the multiple gestations resulting from assisted-reproduction techniques had been singleton pregnancies, the predicted savings to the health care delivery system in the study hospital alone would have been over $3 million per year. Although assisted reproduction provides tremendous benefits to families with infertility, the increased medical risks entailed by multiple-gestation pregnancies and the associated costs cannot be ignored. We suggest that more attention be paid to approaches to infertility that reduce the likelihood of multiple gestation. C1 MASSACHUSETTS GEN HOSP,NATL CTR INFERTIL RES,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT OBSTET GYNECOL,BOSTON,MA. FU NCRR NIH HHS [MO1-RR-01066]; NICHD NIH HHS [U54-HD-29164] NR 40 TC 298 Z9 302 U1 1 U2 11 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 28 PY 1994 VL 331 IS 4 BP 244 EP 249 DI 10.1056/NEJM199407283310407 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NY335 UT WOS:A1994NY33500007 PM 8015572 ER PT J AU WEE, SL STROKA, DM DSOUZA, G FULLER, TC FITZPATRICK, DM COSIMI, AB AF WEE, SL STROKA, DM DSOUZA, G FULLER, TC FITZPATRICK, DM COSIMI, AB TI ANTI-CD4 MAB THERAPY SIGNIFICANTLY DELAYS THE ALLOANTIBODY RESPONSE IN A CYNOMOLGUS RENAL-TRANSPLANT MODEL SO TRANSPLANTATION LA English DT Note ID MONOCLONAL-ANTIBODIES; ALLOGRAFT RECIPIENTS; RHESUS-MONKEYS; INVIVO C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,HISTOCOMPATIBIL LAB,BOSTON,MA 02114. RP WEE, SL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,TRANSPLANTAT UNIT,WHITE 546,BOSTON,MA 02114, USA. RI Stroka, Deborah/F-1806-2013 FU NHLBI NIH HHS [HL-18646] NR 16 TC 4 Z9 4 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 JUL 27 PY 1994 VL 58 IS 2 BP 261 EP 264 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NZ232 UT WOS:A1994NZ23200023 PM 7913778 ER PT J AU DONNELLY, SC HASLETT, C DRANSFIELD, I ROBERTSON, CE CARTER, DC ROSS, JA GRANT, IS TEDDER, TF AF DONNELLY, SC HASLETT, C DRANSFIELD, I ROBERTSON, CE CARTER, DC ROSS, JA GRANT, IS TEDDER, TF TI ROLE OF SELECTINS IN DEVELOPMENT OF ADULT-RESPIRATORY-DISTRESS-SYNDROME SO LANCET LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; ENDOTHELIAL-CELLS; LUNG INJURY; SUPERNATANTS; NEUTROPHILS; RISK AB The acute lung injury of adult respiratory distress syndrome (ARDS) is characterised by inflammatory cell accumulation and activation in the lung. Selectins are a family of adhesion molecules implicated in leucocyte-endothelial adhesion, whose receptors can exist in a cleaved, soluble form. We investigated whether circulating soluble selectin adhesion molecules, obtained from ARDS at-risk patients, were associated with subsequent ARDS development. 82 patients, at risk of ARDS, were enrolled from three well-defined groups (multiple trauma, pancreatitis, perforated bowel). Plasma samples were obtained on hospital presentation and soluble L, E, and P, selectins were quantified with a sandwich enzyme-linked immunosorbent assay (ELISA). 14 patients subsequently developed ARDS. Initial plasma soluble L-selectin (sL-selectin) levels were significantly lower in patients who progressed to ARDS compared to those who did not (p = 0.0001; 95% Cl for mean in ARDS patients as percent of that in non-ARDS patients, 27-61%). Moreover concentrations were lower than in 62 normal volunteers (range 0.37-6.55, median 1.83 mu g/mL, n = 62), suggesting that a selective reduction of sL-selectin correlates with susceptibility. In addition, a significant correlation was found between low values of sL-selectin and indices of subsequent lung injury including requirement for ventilation (p = 0.0001) and degree of respiratory failure (p = 0.0001). A significant correlation was also found between low values of sL-selectin and patient mortality(p = 0.002). These results elucidate the inflammatory cell endothelial interactions in the early stages of ARDS and may be of prognostic value. C1 UNIV EDINBURGH,RAYNE LAB,RESP MED UNIT,EDINBURGH EH8 9AG,MIDLOTHIAN,SCOTLAND. ROYAL INFIRM,DEPT ACCID & EMERGENCY,EDINBURGH,MIDLOTHIAN,SCOTLAND. UNIV EDINBURGH,ROYAL INFIRM,DEPT SURG,EDINBURGH,MIDLOTHIAN,SCOTLAND. WESTERN GEN HOSP,INTENS THERAPY UNIT,EDINBURGH,MIDLOTHIAN,SCOTLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA54464] NR 29 TC 199 Z9 203 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 23 PY 1994 VL 344 IS 8917 BP 215 EP 219 DI 10.1016/S0140-6736(94)92995-5 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA NY060 UT WOS:A1994NY06000007 PM 7518025 ER PT J AU PALLAS, DC FU, H HAEHNEL, LC WELLER, W COLLIER, RJ ROBERTS, TM AF PALLAS, DC FU, H HAEHNEL, LC WELLER, W COLLIER, RJ ROBERTS, TM TI ASSOCIATION OF POLYOMAVIRUS MIDDLE TUMOR-ANTIGEN WITH 14-3-3-PROTEINS SO SCIENCE LA English DT Article ID SMALL T-ANTIGEN; CELLULAR PROTEINS; TRANSFORMATION; PHOSPHATASE-2A; COMPLEXES; FAMILY; CELLS AB To carry out its transformation function, the middle tumor antigen (MT) of murine polyomavirus associates with a number of cellular proteins involved in regulation of cell proliferation, including pp60(c-Src), phosphatidylinositol 3-kinase, protein phosphatase 2A, Src homologous and collagen protein and growth factor receptor-binding protein 2. Here, two additional MT-associated proteins were identified as members of the 14-3-3 family of proteins. Yeast homologs of 14-3-3 proteins have recently been shown to play a role in the timing of mitosis. Thus, regulation of 14-3-3 protein function by MT may contribute to the development of neoplasia. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,SHIPLEY INST MED,BOSTON,MA 02115. RP PALLAS, DC (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115, USA. OI Collier, R John/0000-0002-2427-4239 FU NCI NIH HHS [R01 CA057327, CA30002, CA45285, CA50661] NR 16 TC 162 Z9 165 U1 1 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 22 PY 1994 VL 265 IS 5171 BP 535 EP 537 DI 10.1126/science.8036498 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY216 UT WOS:A1994NY21600034 PM 8036498 ER PT J AU KOWLURU, A RABAGLIA, ME MUSE, KE METZ, SA AF KOWLURU, A RABAGLIA, ME MUSE, KE METZ, SA TI SUBCELLULAR-LOCALIZATION AND KINETIC CHARACTERIZATION OF GUANINE-NUCLEOTIDE-BINDING PROTEINS IN NORMAL RAT AND HUMAN PANCREATIC-ISLETS AND TRANSFORMED BETA-CELLS SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE PANCREATIC ISLET; GTPASE; G PROTEIN; SECRETORY GRANULE; INSULIN SECRETION ID INSULIN-SECRETING CELLS; LOW KM GTPASE; PERTUSSIS TOXIN; GRANULE MEMBRANES; HIT CELLS; CHROMAFFIN CELLS; PLASMA-MEMBRANES; ADP-RIBOSYLATION; CAMP METABOLISM; RINM5F CELLS AB The subcellular localization and the kinetics of the GTPase activities of monomeric and heterotrimeric GTP-binding proteins were investigated in normal rat and human pancreatic islets and were compared to those obtained using a transformed hamster beta cell line (HIT cells). The [alpha-P-32]GTP overlay technique revealed the presence of at least four low-molecular-mass proteins (approx. 20-27 kDa) in normal rat islets, which were enriched in the secretory granule fraction compared to the membrane fraction (with little abundance of these proteins in the cytosolic fraction). In contrast, in HIT cells, these proteins (at least six) were predominantly cytosolic. Three of these proteins were immunologically identified as rab3A, rac2 and CDC42Hs in islets as well as in HIT cells. In addition, pertussis toxin augmented the ribosylation of at least one heterotrimeric G-protein of about 39 kDa (probably G(i) and/or G(0)) in the membrane and secretory granule fractions of normal rat and human islets, whereas at least three such Ptx substrates (36-39 kDa) were found in HIT cell membranes. Kinetic analyses of the intrinsic specific GTPase activities revealed the presence of at least three such activities (K-m for GTP of 372 nM, 2.2 mu M, and 724 mu M) in islet homogenates which were differentially distributed in various subcellular fractions; similar activities were also demonstrable in HIT cell homogenates. Thus, these studies demonstrate the presence of both monomeric as well as trimeric G-proteins intrinsic to the secretory granules of normal rat islets which can be ascribed to beta cells; since these G-proteins are regulated by insulinotropic lipids (as described in the accompanying article), such proteins may couple the activation of phospholipases (endogenous to islets) to the exocytotic secretion of insulin. These findings also suggest that caution is necessary in extrapolating data concerning G-proteins from cultured, transformed beta cell lines to the physiology of normal islets, in view of both qualitative and quantitative differences between the two preparations. C1 UNIV WISCONSIN,SCH MED,ENDOCRINOL SECT,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT PATHOL,MADISON,WI 53705. RP KOWLURU, A (reprint author), UNIV WISCONSIN,SCH MED,DEPT MED,H4-568 CLIN SCI CTR 600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NIDDK NIH HHS [DK37312] NR 70 TC 38 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUL 21 PY 1994 VL 1222 IS 3 BP 348 EP 359 DI 10.1016/0167-4889(94)90040-X PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PA034 UT WOS:A1994PA03400004 PM 8038203 ER PT J AU KOWLURU, A METZ, SA AF KOWLURU, A METZ, SA TI REGULATION OF GUANINE - NUCLEOTIDE-BINDING PROTEINS IN ISLET SUBCELLULAR-FRACTIONS BY PHOSPHOLIPASE-DERIVED LIPID MEDIATORS OF INSULIN-SECRETION SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE G PROTEIN; INSULIN SECRETION; LIPID MESSENGER; PANCREATIC ISLET; SECRETORY GRANULE; GTPASE ID PERMEABILIZED RAT ISLETS; ARACHIDONIC-ACID; PANCREATIC-ISLETS; GTPASE ACTIVITY; CHROMAFFIN GRANULES; CA-2+ MOBILIZATION; PLASMA-MEMBRANES; DUAL MECHANISMS; NADPH OXIDASE; RELEASE AB In the accompanying article (Kowluru, A., Rabaglia, M.E., Mose, K.E. and Metz, S.A. (1994) Biochim. Biophys. Acta 1222, 348-359) we identified three specific GTPase activities in islet subcellular fractions; most notably, two of these were enriched in the secretory granules. In the present study, we describe the regulation of GTPase activity in subcellular fractions of normal rat and human islets by insulinotropic lipids with a similar rank order as their insulin-releasing capacity. Arachidonic acid (AA), lysophosphatidylcholine (LPC), or phosphatidic acid (PA) inhibited the GTPase activities significantly (by 60-80%) in isIet homogenates; each also selectively inhibited certain GTPases in specific individual fractions. Less insulinotropic fatty acids, such as linoleic acid and oleic acid, inhibited GTPase to a lesser degree, whereas lysophosphatidic acid (LPA), phosphatidylcholine (PC) or palmitic acid, which do not acutely promote secretion, were ineffective. Similar inhibitory effects of these lipids were also demonstrable in fractions of human islets as well as those of transformed beta-cells (HIT cells). The effects of lipids were not attributable to their detergent properties (since several detergents failed to mimic lipid effects) or to inhibition of GTP binding (since they actually increased GTP gamma S binding modestly, and moreover, in reconstituted fractions, they potentiated GDP/GTP exchange activity up to 2-fold). These data indicate that the insulinotropic nature of the lipids might be due, in part, to their ability to maintain G-proteins in their GTP-bound (active) configuration by increasing GTP binding and decreasing its hydrolysis. These studies comprise the first evidence for the regulation by biologically active lipids of endocrine cell G-proteins at a locus distal to plasma membrane events (i.e., on endocrine secretory granules), and provide thereby a possible novel mechanism whereby the activation of islet endogenous phospholipases might culminate in insulin exocytosis. C1 UNIV WISCONSIN,SCH MED,ENDOCRINOL SECT,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. RP KOWLURU, A (reprint author), UNIV WISCONSIN,SCH MED,DEPT MED,H4-568 CLIN SCI CTR,600 HIGHLAND AVE,MADISON,WI 53792, USA. FU NIDDK NIH HHS [DK 37312] NR 43 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUL 21 PY 1994 VL 1222 IS 3 BP 360 EP 368 DI 10.1016/0167-4889(94)90041-8 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PA034 UT WOS:A1994PA03400005 PM 8038204 ER PT J AU BERGWITZ, C ABOUSAMRA, AB HESCH, RD JUPPNER, H AF BERGWITZ, C ABOUSAMRA, AB HESCH, RD JUPPNER, H TI RAPID DESENSITIZATION OF PARATHYROID-HORMONE DEPENDENT ADENYLATE-CYCLASE IN PERIFUSED HUMAN OSTEOSARCOMA CELLS (SAOS-2) SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE PARATHYROID HORMONE, PTH; PTH RECEPTOR DESENSITIZATION; PERIFUSION CULTURE; (OSTEOSARCOMA CELL, SAOS-2); (HUMAN) ID OSTEOBLAST-LIKE CELLS; PROTEIN KINASE-C; ANTERIOR-PITUITARY CELLS; CYCLIC-AMP PRODUCTION; DOWN-REGULATION; BONE-CELLS; ALKALINE-PHOSPHATASE; RECEPTOR-BINDING; CAMP PRODUCTION; SARCOMA CELLS AB The pulsatile but not the continuous application of parathyroid hormone (PTH) increases bone mass in vivo. To study the effects of intermittent hormonal administration on bone-derived cells in vitro, we established a perifusion system using the human osteosarcoma cell line SaOS-2. Cells were grown in suspension culture attached to collagen beads and were then loaded into a 3 ml syringe for perifusion experiments. The application of PTH(1-34) resulted in a dose-dependent increase of cAMP release by SaOS-2 cells into the effluent medium. Cyclic AMP accumulation was rapidly desensitized by approx. 80% after 30 min of continuous exposure to PTH(1-34) (10(-7) M), while cells remained responsive to forskolin. The recovery of PTH responsiveness required at least 2 h of hormone-free perifusion. Desensitization in the experimental setting was dose-dependent (EC(50) = 1.10(-10) M PTH(1-34)). Neither 8Br-cAMP (2.10(-4) M) nor PMA (1.10(-7) M) had an effect on the PTH(1-34)-induced desensitization of the adenylate cyclase. Radioreceptor assays showed that [I-125]-[Tyr(36)]hPTHrP(1-36)amide binding to SaOS-2 cells was decreased by 60-70% by PTH(1-34) (1.10(-6) M), bPTH(1-84) (1.8.10(-6) M) and bPTH(3-34) (2.10(-6) M), whereas 8Br-cAMP (2.10(-4) M) had no effect on radioligand binding. PMA (1.10(-7) M) appeared to slightly increase [I-125]PTHrP binding. This observation is consistent with a small (3-fold) increase in PTH-induced cAMP release as a result of PMA pre-treatment. Receptor internalization was dose-dependent (EC(50) = 3.10(-7) M PTH(1-34)). The maximal effect occurred after 10-30 min and was largely reversible within 2 h. Monensin (3.10(-5) M) inhibited the recovery from receptor internalization. We conclude that a perifusion system using SaOS-2 cells is a suitable model to study the effect of discontinuous application of PTH on cAMP release. A rapid, homologous desensitization of PTH(1-34) stimulated cAMP accumulation has been observed that does not appear to involve protein kinase A or C. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PEDIAT,ENDOCRINE UNIT,BOSTON,MA 02114. HANNOVER MED SCH,ZENTRUM INNERE MED,KLIN ENDOKRINOL ABT,D-30625 HANNOVER,GERMANY. RP BERGWITZ, C (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114, USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK 11794] NR 57 TC 21 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUL 21 PY 1994 VL 1222 IS 3 BP 447 EP 456 DI 10.1016/0167-4889(94)90053-1 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PA034 UT WOS:A1994PA03400017 PM 8038214 ER PT J AU JACOX, A CARR, DB PAYNE, R AF JACOX, A CARR, DB PAYNE, R TI TREATING CANCER PAIN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MD ANDERSON CANC HOSP,HOUSTON,TX 77030. RP JACOX, A (reprint author), JOHNS HOPKINS UNIV,SCH NURSING,BALTIMORE,MD 21205, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 21 PY 1994 VL 331 IS 3 BP 201 EP 201 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NW797 UT WOS:A1994NW79700021 ER PT J AU HALL, JE TAYLOR, AE MARTIN, KA RIVIER, J SCHOENFELD, DA CROWLEY, WF AF HALL, JE TAYLOR, AE MARTIN, KA RIVIER, J SCHOENFELD, DA CROWLEY, WF TI DECREASED RELEASE OF GONADOTROPIN-RELEASING-HORMONE DURING THE PREOVULATORY MIDCYCLE LUTEINIZING-HORMONE SURGE IN NORMAL WOMEN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MENSTRUAL CYCLE; NEUROENDOCRINE; FOLLICLE-STIMULATING HORMONE; GONADOTROPIN-RELEASING HORMONE ANTAGONIST ID FOLLICLE-STIMULATING-HORMONE; RAT ESTROUS-CYCLE; MENSTRUAL-CYCLE; RHESUS-MONKEY; NEUROENDOCRINE REGULATION; DYNAMIC REGULATION; GNRH SECRETION; CORPUS-LUTEUM; ACTIVIN-A; PITUITARY AB To investigate the contribution of hypothalamic gonadotropin-releasing hormone (GnRH) secretion to the midcycle gonadotropin surge in the human, the response of luteinizing hormone (LH) to competitive GnRH receptor blockade achieved by administration of a range of doses of a pure GnRH antagonist was used to provide a semiquantitative estimate of endogenous GnRH secretion. The LH response to 5, 15, 50, and 150 mu g/kg s.c. of the NAL-GLU GnRH antagonist ([Ac-D-2Nal(1),D-4ClPhe(2),D-Pal(3),Arg(5),D-4-p-methoxybenzoyl-2-aminobutyric acid(6),D-Ala(10)]GnRH, where 2Nal is 2-naphthylalanine, 4ClPhe is 4-chlorophenylalanine, and 3Pal is 3-pyridylalanine) was measured in normal women in the early and late follicular phases of the menstrual cycle, at the time of the midcycle LH surge and in the early luteal phase. LH decreased in a dose-response fashion after administration of the GnRH antagonist in all cycle phases (P < 0.0001). When this suppression was expressed as maximum percent inhibition, there was no difference in response during the early and late follicular and early luteal phases. However, at the midcycle surge, there was a leftward shift of the dose-response curve with significantly greater suppression of LH at the lower antagonist doses in comparison to the other cycle phases (P < 0.005), but no difference at the highest dose. Thus, we draw the following conclusions. (i) There is a consistently greater degree of LH inhibition by GnRH antagonism at the midcycle surge at submaximal degrees of GnRH receptor blockade than at other phases of the menstrual cycle in normal women. (ii) This leftward shift of the dose-response relationship to GnRH receptor blockade suggests that the overall amount of GnRH secreted at the midcycle surge is less than at other cycle stages. (iii) These data confirm the importance of pituitary augmentation of the GnRH signal at the time of the midcycle gonadotropin surge in the human. C1 MASSACHUSETTS GEN HOSP, CTR REPROD ENDOCRINE SCI, DEPT MED, BOSTON, MA 02114 USA. SALK INST BIOL STUDIES, LA JOLLA, CA 92037 USA. RP MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BOSTON, MA 02114 USA. FU NICHD NIH HHS [N01-HD-32837, U54-HD-29164, U54 HD029164, R01-HD-15080, P30 HD028138] NR 39 TC 60 Z9 61 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 1994 VL 91 IS 15 BP 6894 EP 6898 DI 10.1073/pnas.91.15.6894 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800031 PM 8041716 ER PT J AU BOUSSIOTIS, VA NADLER, LM STROMINGER, JL GOLDFELD, AE AF BOUSSIOTIS, VA NADLER, LM STROMINGER, JL GOLDFELD, AE TI TUMOR-NECROSIS-FACTOR-ALPHA IS AN AUTOCRINE GROWTH-FACTOR FOR NORMAL HUMAN B-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN T-CELLS; FACTOR CACHECTIN; MONOCLONAL-ANTIBODIES; FACTOR RECEPTORS; GENE-REGULATION; CYCLOSPORINE-A; LYMPHOCYTES-B; TNF-ALPHA; ACTIVATION; LYMPHOTOXIN AB Transcription of the human tumor necrosis factor alpha (TNF-alpha) gene is one of the earliest events that occurs after stimulation of B or T cells via their antigen receptors. Antibody directed at surface immunoglobulin (anti-Ig) on B cells has previously been shown to induce a rapid burst of TNF-alpha gene transcription, which can be blocked by the immunosuppressants cyclosporin A (CsA) and FK506. Here, TNF-alpha gene transcription is shown also to be highly and rapidly induced in human B cells after stimulation via the CD40 and interleukin 4 pathways, which similarly is inhibited by CsA and a panel of CsA or FK506 analogues that block calcineurin phosphatase activity. Endogenous TNF-alpha produced after stimulation was involved in B-cell proliferation since anti-TNF-alpha monoclonal antibody inhibited both anti-Ig- and anti-CD40-induced B-cell proliferative responses. Moreover, addition of TNF-alpha during stimulation resulted in augmentation of B-cell proliferation, which was also inhibited by anti-TNF-alpha monoclonal antibody. Although lymphotoxin alpha (LT-alpha) mRNA is induced by both pathways, it is not blocked by CsA, whereas LT-beta mRNA is constitutively expressed in B cells. Thus, TNF-alpha is a necessary autocrine growth factor for human B cells stimulated via two independent CsA-sensitive pathways and plays a role similar to that of interleukin 2 in T-cell proliferation. The autocrine nature of TNF-alpha in activated B cells implies a potential role for this cytokine in infection-related polyclonal B-cell expansion and in B cell malignancies. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. FU NCI NIH HHS [CA-58735, CA47554] NR 48 TC 119 Z9 119 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 1994 VL 91 IS 15 BP 7007 EP 7011 DI 10.1073/pnas.91.15.7007 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800054 PM 7518925 ER PT J AU WANG, CY STILES, CD AF WANG, CY STILES, CD TI PLATELET-DERIVED GROWTH-FACTOR-ALPHA RECEPTOR GENE-EXPRESSION - ISOLATION AND CHARACTERIZATION OF THE PROMOTER AND UPSTREAM REGULATORY ELEMENTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TRANSCRIPTION; GROWTH FACTOR RECEPTOR ID GLIOMA CELL-LINES; RETINOIC ACID; CYCLIC-AMP; FACTOR-A; PDGF-A; INDUCTION; DIFFERENTIATION; CHAIN; PREIMPLANTATION; EMBRYOGENESIS AB Receptors for the platelet derived growth factors (PDGFs) are expressed conditionally in developing embryos and adult tissues. Aberrant expression of PDGF receptors is a molecular marker for proliferative disorders such as atherosclerosis, myofibrosis, and malignant astrocytoma. We isolated genomic clones that encompass the 5' end of the mouse PDGF alpha receptor mRNA transcript and extend 10 kb into the upstream flanking region of the gene. Using these clones, we constructed a partial genomic map that locates the promoter and transcription start sites of the gene. One of our genomic clones contains cis-acting regulatory elements that drive expression of reporter gene constructs selectively in cells that express PDGF alpha receptors. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MICROBIOL & MOLEC GENET,DIV CELLULAR & MOLEC,BOSTON,MA 02115. FU NCI NIH HHS [CA 22042]; NIGMS NIH HHS [GM 31489] NR 28 TC 28 Z9 28 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 1994 VL 91 IS 15 BP 7061 EP 7065 DI 10.1073/pnas.91.15.7061 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NY348 UT WOS:A1994NY34800065 PM 8041746 ER PT J AU PAYLOR, R JOHNSON, RS PAPAIOANNOU, V SPIEGELMAN, BM WEHNER, JM AF PAYLOR, R JOHNSON, RS PAPAIOANNOU, V SPIEGELMAN, BM WEHNER, JM TI BEHAVIORAL-ASSESSMENT OF C-FOS MUTANT MICE SO BRAIN RESEARCH LA English DT Article DE LEARNING AND MEMORY; GENETICS; TRANSGENIC MOUSE ID LONG-TERM POTENTIATION; IMMEDIATE EARLY GENES; RAT-BRAIN; SUPRACHIASMATIC NUCLEUS; NERVOUS-SYSTEM; MESSENGER-RNA; TRANSCRIPTION FACTORS; SENSORY STIMULATION; CHICK FOREBRAIN; GRANULE CELLS AB Induction of the proto-oncogene c-fos has been associated with a number of neural and behavioral responses to acute stimuli. Behavioral characterization of mice containing a mutant c-fos allele created via homologous recombination-based gene targeting was performed to analyze the role of this protein in baseline neurological properties as well as paradigms that require neural adaptive responses. Performance of 9 out of 11 c-fos-deficient animals was impaired in the spatial version of the Morris water task. However, this poor performance in the spatial version of the task was highly correlated to their performance in the non-spatial version of the task which suggests that they have a behavioral impairment that interrupts their ability to perform adequately on bath versions of the task with the same proficiency as wild-type and heterozygous litter mates. To examine learning impairments further, a simple left/right discrimination in a T-maze was used. Mutants were not impaired in this simple learning task. These results suggest that c-fos mutants have some behavioral impairments that interfere with evaluation of complex learning on the Morris water task, but because all genotypes could perform a simple discrimination task, it is clear that c-fos is not essential for this simpler form of learning and memory. C1 TUFTS UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02111. TUFTS UNIV,SCH VET MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV COLORADO,INST BEHAV GENET,BOULDER,CO 80309. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. OI Johnson, Randall/0000-0002-4084-6639 FU NIAAA NIH HHS [AA-03527]; NICHD NIH HHS [HD-27295]; NIMH NIH HHS [MH-48663] NR 41 TC 58 Z9 59 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 18 PY 1994 VL 651 IS 1-2 BP 275 EP 282 DI 10.1016/0006-8993(94)90707-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NX150 UT WOS:A1994NX15000034 PM 7922576 ER PT J AU HEBERT, JR HURLEY, TG HSIEH, J ROGERS, E STODDARD, AM SORENSEN, G NICOLOSI, RJ AF HEBERT, JR HURLEY, TG HSIEH, J ROGERS, E STODDARD, AM SORENSEN, G NICOLOSI, RJ TI DETERMINANTS OF PLASMA VITAMINS AND LIPIDS - THE WORKING WELL STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CAROTENE; CHOLESTEROL; DIET; PLASMA; VITAMIN-A; VITAMIN-E ID FOOD-FREQUENCY QUESTIONNAIRE; ALPHA-TOCOPHEROL LEVELS; SERUM BETA-CAROTENE; LUNG-CANCER; LIPOPROTEIN CHOLESTEROL; DIETARY QUESTIONNAIRE; A INTAKE; VALIDATION; RISK; SUPPLEMENTATION AB This study was conducted to assess the determinants of plasma concentrations of alpha-tocopherol, beta-carotene, retinol, and cholesterol fractions in a randomly selected subset of 203 workers participating in a worksite-based health intervention trial. Workers were from four companies in eastern and central Massachusetts, and all completed an 84-item semiquantitative food frequency questionnaire as part of baseline (preintervention) self-assessment instruments. At the time of fasting blood sampling, each participant also completed a short screening questionnaire for assessment of changes in dietary habits and tobacco exposure and for collection of data on use of vitamins and nutritional supplements. On the basis of the self-reported data, the authors found that they could explain 35% of the variability in plasma beta-carotene, 73% of the variability in alpha-tocopherol, 36% of the variability in retinol, and 19% of the variability in cholesterol. Plasma beta-carotene levels appeared to be affected by the use of supplements that did not contain carotene, indicating a beta-carotene sparing capability of other agents contained in these preparations. Plasma alpha-tocopherol levels were not similarly affected. These results compare favorably with those from studies that used more intensive dietary assessment techniques as the comparison criterion. Results are discussed in terms of implications for use of self-reported data in epidemiologic study analyses. C1 DANA FARBER CANC INST,DIV EPIDEMIOL & CONTROL,BOSTON,MA. UNIV MASSACHUSETTS,COLL HLTH PROFESS,DEPT CLIN LAB SCI,LOWELL,MA. UNIV MASSACHUSETTS,SCH PUBL HLTH & HLTH SCI,DEPT BIOSTAT & EPIDEMIOL,AMHERST,MA 01003. RP HEBERT, JR (reprint author), UNIV MASSACHUSETTS,SCH MED,DIV PREVENT & BEHAV MED,55 LAKE AVE N,WORCESTER,MA 01655, USA. FU NCI NIH HHS [U01 CA51671, U01 CA51686, U01 CA51687] NR 63 TC 52 Z9 52 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 15 PY 1994 VL 140 IS 2 BP 132 EP 147 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NX125 UT WOS:A1994NX12500005 PM 8023802 ER PT J AU SCHECTER, AD CHESEBRO, JH FUSTER, V AF SCHECTER, AD CHESEBRO, JH FUSTER, V TI REFRACTORY PRINZMETAL ANGINA TREATED WITH CYPROHEPTADINE SO ANNALS OF INTERNAL MEDICINE LA English DT Note ID SEROTONIN; ENDOTHELIUM; PIGS C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 10 TC 7 Z9 7 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 JUL 15 PY 1994 VL 121 IS 2 BP 113 EP 114 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NW186 UT WOS:A1994NW18600006 PM 8017723 ER PT J AU CARLSON, KJ SKATES, SJ SINGER, DE AF CARLSON, KJ SKATES, SJ SINGER, DE TI SCREENING FOR OVARIAN-CANCER SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID SERUM CA-125 LEVELS; TUMOR-ASSOCIATED ANTIGEN; PELVIC MASSES; PREOPERATIVE EVALUATION; FAMILY HISTORY; PROPHYLACTIC OOPHORECTOMY; POSTMENOPAUSAL WOMEN; EPITHELIAL CARCINOMA; STAGE-I; CA 125 AB Purpose: To critically review the available evidence for screening asymptomatic women for ovarian cancer with ultrasonography or the CA 125 radioimmunoassay (CA 125) or both. Data Sources: A MEDLINE search of the English-language literature and bibliographies of published studies providing estimates of ovarian cancer risk and test operating characteristics (based on observational studies and meta-analyses) and effectiveness of treatment according to stage of disease (based on randomized trials). Published mathematical models simulating screening for ovarian cancer in specific populations were also included. Death from ovarian cancer and morbidity from surgical procedures were the principal outcomes considered. Results: Age and family history are the most important risk factors for ovarian cancer. Annual screening with CA 125 or ultrasound in women older than 50 years without a family history of ovarian cancer would result in more than 30 false-positive results for every ovarian cancer detected. False-positive tests are likely to require invasive testing, often including laparotomy. There is currently no direct evidence that mortality from ovarian cancer would be decreased by screening. Conclusions: Available evidence does not support either screening of pre- or postmenopausal women without a family history of ovarian cancer or routine screening in women with a family history of ovarian cancer in one or more relatives (without evidence of a hereditary cancer syndrome). Women from a family with the rare hereditary ovarian cancer syndrome are at high risk for the disease and should be referred to a gynecologic oncologist. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP CARLSON, KJ (reprint author), MASSACHUSETTS GEN HOSP,CTR MED PRACTICES EVALUAT,BOSTON,MA 02114, USA. NR 83 TC 82 Z9 85 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 1994 VL 121 IS 2 BP 124 EP 132 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA NW186 UT WOS:A1994NW18600009 PM 8017726 ER PT J AU BELMAKER, RH BIEDERMAN, J AF BELMAKER, RH BIEDERMAN, J TI GENETIC-MARKERS, TEMPERAMENT, AND PSYCHOPATHOLOGY SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID CHILDREN; PARENTS C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RP BELMAKER, RH (reprint author), BEER SHEVA MENTAL HLTH CTR,POB 4600,BEER SHEVA,ISRAEL. NR 7 TC 14 Z9 14 U1 0 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 JUL 15 PY 1994 VL 36 IS 2 BP 71 EP 72 DI 10.1016/0006-3223(94)91186-X PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NX838 UT WOS:A1994NX83800001 PM 7948448 ER PT J AU QUINTANILLAMARTINEZ, L WILKINS, EW CHOI, N EFIRD, J HUG, E HARRIS, NL AF QUINTANILLAMARTINEZ, L WILKINS, EW CHOI, N EFIRD, J HUG, E HARRIS, NL TI THYMOMA - HISTOLOGIC SUBCLASSIFICATION IS AN INDEPENDENT PROGNOSTIC FACTOR SO CANCER LA English DT Article DE THYMOMA CLASSIFICATION; PROGNOSIS; THYMUS; TUMOR; THYMIC CARCINOMA; PATHOLOGY; SURGERY; RADIATION ONCOLOGY ID DIFFERENTIATED THYMIC CARCINOMA; INVASIVE THYMOMA; MALIGNANT THYMOMA; RADIATION-THERAPY; CLINICAL STAGES; FEATURES; CHEMOTHERAPY; MANAGEMENT AB Background. Several histologic classifications of thymomas have been proposed, and attempts have been made to correlate the different histologic subtypes to clinical behavior and prognosis. Recently, Marine and Muller-Hermelink and Kirchner et al. proposed a new morphologic classification of thymomas based on the resemblance of the neoplastic cells to subtypes of the normal thymic epithelial cells. In this classification, six categories of thymic epithelial tumors are recognized. They define four categories of thymoma: medullary, mixed, organoid (predominantly cortical), and cortical, and two subgroups of thymic carcinomas: well differentiated thymic carcinoma and high grade carcinomas. Methods. The authors studied 116 patients with thymic epithelial tumors classified according to the proposals of Marine and Muller-Hermelink and Kirchner et al. to assess the effect of histologic classification and other factors (stage, size of tumor, lymphoid hyperplasia, myasthenia gravis, age, sex, and treatment) on survival, and freedom from relapse. Results. Eight cases (7%) were medullary, 32 cases (28%) mixed, 20 cases (17%) organoid (predominantly cortical), 21 cases (18%) cortical, 29 cases (25%) well differentiated carcinoma (WDTC), two cases (2%) high grade carcinoma, and four cases (3%) unclassifiable. Fifty-two patients were in stage I, 32 stage II (16 IIA, 16 IIB), 28 stage III, and four Stage IVA. Only stage (P = 0.0001; hazard ratio = 5.36) and histology (P = 0.0019; hazard ratio = 8.010) were significant in predicting recurrence. Histology was highly correlated with stage, but by multivariate analysis was an independent factor in predicting relapse (P = 0.0281; hazard ratio = 5.92). None of the medullary or mixed thymomas recurred, even though 30% were invasive. Patients with WDTC recurred more often and earlier than patients with organoid and cortical thymoma (log rank, P = 0.0001). The actuarial freedom from relapse for patients with WDTC was 58% at 5 years and 46% at 10 years compared with 100% for other subtypes. Both advanced stage (III and IV) and the WDTC histologic subtype significantly increased the risk of death from thymoma (log rank, P = 0.0001). The actuarial survival of patients with WDTC was 80% at 5 years and 54% at 10 years, whereas that of patients with the other subtypes was 100% at 5 and 10 years. Five of seven relapses and six of seven deaths from thymoma occurred in patients with WDTC. In Stage II patients, one of 16 minimally invasive (Stage IIA) tumors recurred, compared with 3 of 16 grossly invasive (Stage IIB) tumors, indicating that microscopic assessment of invasion is important in staging. Conclusions. The histologic classification of Marine and Muller-Hermelink has prognostic significance, independent of tumor stage. Medullary and mixed thymomas were benign tumors with no risk of recurrence, even when capsular invasion was present. Organoid and cortical thymoma showed intermediate invasiveness and a low, but significant, risk of late relapse, even with minimal invasion. WDTC were always invasive and had a significantly increased risk of relapse and death, even for Stage II patients. Adjuvant therapy appears unnecessary for medullary and mixed thymomas, even when invasive. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,THORAC SURG UNIT,BOSTON,MA 02114. NR 30 TC 158 Z9 161 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUL 15 PY 1994 VL 74 IS 2 BP 606 EP 617 DI 10.1002/1097-0142(19940715)74:2<606::AID-CNCR2820740212>3.0.CO;2-T PG 12 WC Oncology SC Oncology GA NX371 UT WOS:A1994NX37100011 PM 8033040 ER PT J AU TEICHER, BA HOLDEN, SA LIU, CJT ARA, G HERMAN, TS AF TEICHER, BA HOLDEN, SA LIU, CJT ARA, G HERMAN, TS TI MINOCYCLINE AS A MODULATOR OF CHEMOTHERAPY AND HYPERTHERMIA IN-VITRO AND IN-VIVO SO CANCER LETTERS LA English DT Article DE CHEMOTHERAPY; MINOCYCLINE; HYPERTHERMIA ID HYPOXIC TUMOR-CELLS; COLLAGENASE ACTIVITY; CYTO-TOXICITY; MITOMYCIN-C; ANGIOGENESIS; INVITRO; METASTASIS; MECHANISM; RADIOSENSITIVITY; ENHANCEMENT AB We tested the ability of the collagenase-inhibitor minocycline to increase the effectiveness of CDDP, BCNU and mitomycin C +/- hyperthermia. When tested in vitro in FSaIIC fibrosarcoma cells, exposure to minocycline (100 mu M for 24 h) decreased the CDDP cytotoxicity at 37 degrees C and pH 7.40 in both normally oxygenated and hypoxic cells and decreased the cytotoxicity of CDDP at 42 degrees C or 43 degrees C in normally oxygenated cells while increasing the killing in hypoxic cells. When tested at pH 6.45, the presence of minocycline tended to protect both normally oxygenated and hypoxic cells from the cytotoxic effects of CDDP +/- hyperthermia. With exposure to BCNU, minocycline markedly protected both normally oxygenated and hypoxic cells at 37 degrees C at both pHs. As the temperature during the exposure to BCNU was increased to 42 degrees C or 43 degrees C, the protection afforded by minocycline diminished especially under low pH conditions where BCNU plus 43 degrees C was extremely cytotoxic to both normally oxygenated and hypoxic cells. One hour exposure to mitomycin C was more cytotoxic to hypoxic than normally oxygenated cells under all conditions of pH and temperature tested and the cytotoxicity of mitomycin C under each condition was increased by minocycline. Both CDDP and BCNU were much more cytotoxic toward FSaIIC tumors in vivo when drug administration was followed by local heating (43 degrees C, 30 min) of the tumor bearing limb. In each case, treatment with minocycline had little effect on tumor-cell killing. Treatment with mitomycin C and hyperthermia resulted in additive tumor-cell killing, and minocycline administration further increased that effect. Tumor-growth delay studies in FSaIIC tumor-bearing animals demonstrated that treatment with CDDP, BCNU or mitomycin C produced growth delays which were additive with hyperthermia (43 degrees C, 30 min) and/or minocycline administered daily for 14 days on days 4-18. These results indicate that minocycline, has measurable antitumor and cytotoxic effects under the conditions tested. C1 HARVARD UNIV,SCH MED,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. FU NCI NIH HHS [R01-CA50174, P01-CA31303] NR 28 TC 4 Z9 5 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 15 PY 1994 VL 82 IS 1 BP 17 EP 25 DI 10.1016/0304-3835(94)90141-4 PG 9 WC Oncology SC Oncology GA PH103 UT WOS:A1994PH10300003 PM 8033065 ER PT J AU KREK, W EWEN, ME SHIRODKAR, S ARANY, Z KAELIN, WG LIVINGSTON, DM AF KREK, W EWEN, ME SHIRODKAR, S ARANY, Z KAELIN, WG LIVINGSTON, DM TI NEGATIVE REGULATION OF THE GROWTH-PROMOTING TRANSCRIPTION FACTOR E2F-1 BY A STABLY BOUND CYCLIN A-DEPENDENT PROTEIN-KINASE SO CELL LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; CELL-CYCLE; DIHYDROFOLATE-REDUCTASE; S-PHASE; VIRAL ONCOPROTEINS; COMPLEX-FORMATION; BINDING PROTEIN; IDENTIFICATION; CLONING; P107 AB Cyclin A-kinase, an enzyme required for coordinating S phase progression, forms stable in vivo complexes with E2F-1, a growth-promoting transcription factor, which binds to the retinoblastoma gene product and is involved in the timely activation of genes whose products contribute to G1 exit and S phase traversal. Complex formation results in a negative biochemical effect of cyclin A-kinase: the shut-off of E2F-1-dependent DNA binding function in S/G2. Thus, specific and timely cell cycle-dependent interactions of E2F-1 with proteins that inhibit its function (i.e., RB during G1 and cyclin A-kinase during S/G2) may contribute to the periodicity of expression of certain E2F-1-responsive genes at the G1/S transition. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP KREK, W (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 44 TC 432 Z9 439 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 15 PY 1994 VL 78 IS 1 BP 161 EP 172 DI 10.1016/0092-8674(94)90582-7 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NX328 UT WOS:A1994NX32800018 PM 8033208 ER PT J AU JACOBY, RF HOHMAN, C MARSHALL, DJ FRICK, TJ SCHLACK, S BRODA, M SMUTKO, J ELLIOTT, RW AF JACOBY, RF HOHMAN, C MARSHALL, DJ FRICK, TJ SCHLACK, S BRODA, M SMUTKO, J ELLIOTT, RW TI GENETIC-ANALYSIS OF COLON-CANCER SUSCEPTIBILITY IN MICE SO GENOMICS LA English DT Article ID MULTIPLE INTESTINAL NEOPLASIA; COLORECTAL-CANCER; INBRED STRAINS; APC GENE; MOUSE; 1,2-DIMETHYLHYDRAZINE; MUTATIONS; LINKAGE; MAP; CARCINOGENESIS AB Mouse models may aid in the identification of genes involved in colon cancer. Our mating scheme involved mouse strains selected for maximum differences in susceptibility to DMH-induced colon tumors, Tumors were found in 40 of 122 progeny from a backcross to the resistant strain. We examined progeny animals for segregation of 177 genetic markers distributed at intervals of 5-30 cM on all mouse chromosomes. Multiple loci contribute to the phenotype, with significant linkage to a novel locus, Ccs1, between D12Mit5 and D12Mit6 on mouse Chr 12. Comparative maps suggest that the human homologue of Ccs1 is near FOS on human chromosome 14q. (C) 1994 Academic Press, Inc. C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53792. UNIV WISCONSIN,SCH MED,CTR COMPREHENS CANC,MADISON,WI 53792. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53705. ROSWELL PK CANC INST,DEPT MOLEC & CELLULAR BIOL,BUFFALO,NY 14263. RP JACOBY, RF (reprint author), UNIV WISCONSIN,SCH MED,GASTROENTEROL SECT,H6-516 CLIN SCI CTR,600 HIGHLAND AVE,MADISON,WI 53792, USA. NR 39 TC 67 Z9 67 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL 15 PY 1994 VL 22 IS 2 BP 381 EP 387 DI 10.1006/geno.1994.1399 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PB571 UT WOS:A1994PB57100018 PM 7806225 ER PT J AU FRIEND, S AF FRIEND, S TI P53 - A GLIMPSE AT THE PUPPET BEHIND THE SHADOW PLAY SO SCIENCE LA English DT Editorial Material ID WILD-TYPE P53; BINDING PROTEIN; MUTATIONS C1 HARVARD UNIV,SCH MED,BOSTON,MA 02129. RP FRIEND, S (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129, USA. NR 17 TC 146 Z9 148 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 15 PY 1994 VL 265 IS 5170 BP 334 EP 335 DI 10.1126/science.8023155 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NW816 UT WOS:A1994NW81600024 PM 8023155 ER PT J AU HARRINGTON, D CROWLEY, J GEORGE, SL PAJAK, T REDMOND, C WIEAND, S AF HARRINGTON, D CROWLEY, J GEORGE, SL PAJAK, T REDMOND, C WIEAND, S TI THE CASE AGAINST INDEPENDENT MONITORING COMMITTEES SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Early Stopping Rules in Cancer Clinical Trials CY APR 13-15, 1993 CL ROBINSON COLL, CAMBRIDGE, ENGLAND HO ROBINSON COLL C1 FRED HUTCHINSON CANC RES CTR,BETHESDA CTR,SW ONCOL GRP,CTR STAT,SEATTLE,WA 98104. DUKE UNIV,MED CTR,CALGB,CTR STAT,DURHAM,NC 27710. UNIV PITTSBURGH,NSABP,CTR STAT,PITTSBURGH,PA 15261. MAYO CLIN & MAYO FDN,N CENT CANC TREATMENT GRP,CTR STAT,ROCHESTER,MN 55905. RP HARRINGTON, D (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR CIVIL ENGN,EASTERN COOPERAT ONCOL GRP,BOSTON,MA 02115, USA. NR 4 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1994 VL 13 IS 13-14 BP 1411 EP 1414 DI 10.1002/sim.4780131316 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA PA168 UT WOS:A1994PA16800014 PM 7973220 ER PT J AU DAMICO, DJ AF DAMICO, DJ TI MEDICAL PROGRESS - DISEASES OF THE RETINA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; DIABETIC MACULAR EDEMA; IMMUNE-DEFICIENCY-SYNDROME; CYTOMEGALO-VIRUS RETINITIS; GRID LASER PHOTOCOAGULATION; PARS-PLANA VITRECTOMY; SUBFOVEAL NEOVASCULAR MEMBRANES; RETICULUM-CELL SARCOMA; PROLIFERATIVE VITREORETINOPATHY; CHOROIDAL NEOVASCULARIZATION C1 HARVARD UNIV, SCH MED, DEPT OPHTHALMOL, BOSTON, MA USA. RP DAMICO, DJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM, DEPT OPHTHALMOL, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 139 TC 51 Z9 56 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 14 PY 1994 VL 331 IS 2 BP 95 EP 106 DI 10.1056/NEJM199407143310207 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA NW712 UT WOS:A1994NW71200007 PM 8208273 ER PT J AU LYNCH, TJ HARRIS, NL MCLOUD, TC SPITZER, TR AF LYNCH, TJ HARRIS, NL MCLOUD, TC SPITZER, TR TI A 41-YEAR-OLD WOMAN WITH NEUROLOGIC ABNORMALITIES AND AN OSTEOLYTIC LESION IN THE MANDIBLE - BURKITTS-LYMPHOMA INVOLVING MANDIBLE, LYMPH-NODES, BONE-MARROW, (SPLEEN), AND QUESTIONABLE NERVOUS-SYSTEM SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID EATON MYASTHENIC SYNDROME; PERIPHERAL NEUROPATHY; DISEASE; NEURONOPATHY; CHILDREN; ANTIGEN; SARCOMA; CANCER; LOCUS; FORMS C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP LYNCH, TJ (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 35 TC 3 Z9 3 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 14 PY 1994 VL 331 IS 2 BP 107 EP 113 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NW712 UT WOS:A1994NW71200008 ER PT J AU BOGDANOV, AA MARTIN, C WEISSLEDER, R BRADY, TJ AF BOGDANOV, AA MARTIN, C WEISSLEDER, R BRADY, TJ TI TRAPPING OF DEXTRAN-COATED COLLOIDS IN LIPOSOMES BY TRANSIENT BINDING TO AMINOPHOSPHOLIPID - PREPARATION OF FERROSOMES SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE LIPOSOME; PHOSPHATIDYLETHANOLAMINE; IRON OXIDE; MAGNETITE; DEXTRAN ID GADOLINIUM-LABELED LIPOSOMES; REVERSE-PHASE EVAPORATION; MR CONTRAST AGENTS; SURFACE; LIVER; MAGNETOLIPOSOMES; DERIVATIVES; PARTICLES; MEMBRANES; REAGENT AB A procedure is described that allows to increase the efficiency of the loading of liposomes with dextran-stabilized iron oxides (MION). The method produces a preparation of liposomes (REVs) with high iron oxide content as a result of transient binding of oxidized dextran with aminogroups of aminophospholipids. Phosphatidylethanolamine (PE)-containing lipid mixtures (PC/DOPE/CH or SM/DOPE/CH, 9:2:9 molar ratio) in organic phase were combined with oxidized MION at pH 8. Liposomes then were obtained by reversed-phase evaporation. Liposomes, 263 +/- 89 nm in diameter, contained up to 11.8 mol Fe/mol phospholipid (encapsulation yield 49%). 10.2% of liposome-associated iron was dissociated from liposomes upon changing the pH to 4.5. When lipid compositions of extracts prepared from liposomes incubated at pH 4.5 and pH 8.0 were compared, an increase of relative PE-content in extracts of liposomes incubated at lowered pH was detected. This indicates a dissociation of imine bonds between aldehydes on the MION surface and PE. The accessibility of liposomal PE for acylation was demonstrated by modification with an activated ester of methoxy poly(ethylene glycol) succinate. Control liposomes, containing no aminophospholipid, or PE-containing liposomes obtained in the presence of non-oxidized MION, were 3.5-5-fold less effective for MION encapsulation and showed extensive aggregation. RP BOGDANOV, AA (reprint author), MASSACHUSETTS GEN HOSP,CTR NUCL MAGNET RESONANCE,DEPT RADIOL,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [R01 CA59649-01] NR 31 TC 54 Z9 55 U1 3 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD JUL 13 PY 1994 VL 1193 IS 1 BP 212 EP 218 DI 10.1016/0005-2736(94)90350-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NY405 UT WOS:A1994NY40500026 PM 7518693 ER PT J AU SWEITZER, BJ CULLEN, DJ AF SWEITZER, BJ CULLEN, DJ TI HOW WELL DOES A JOURNALS PEER-REVIEW PROCESS FUNCTION - A SURVEY OF AUTHORS OPINIONS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 2nd International Congress on Peer Review in Biomedical Publication CY SEP 09-11, 1993 CL AMER MED ASSOC, CHICAGO, IL HO AMER MED ASSOC ID MANUSCRIPTS AB Objective.-To evaluate the authors' satisfaction or dissatisfaction with the peer review process of the Journal of Clinical Anesthesia. Design.-Anonymous questionnaires were sent to authors to survey their opinions about specific aspects of the peer review process. Authors were grouped by status of their manuscripts: AR (accept with revision), RR (reject but may resubmit), and RO (reject outright). Participants.-Authors of unsolicited manuscripts submitted in 1991 to 1992. Main Outcome Measures.-Factors that determine authors' satisfaction with the relevancy and benefit of peer review of their manuscript. Results.-Significantly more authors of AR manuscripts responded to our survey than did authors of rejected manuscripts and viewed the review process more favorably. Authors of AR manuscripts were more satisfied with specific aspects of the review process, which led to improvement in their manuscripts. More authors of RR manuscripts believed that our review process improved subsequent manuscript preparation than did authors of accepted manuscripts. Conclusions.-The surveying of authors, important clients of the peer review process, should guide change necessary to better serve our authors and improve peer review. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 9 TC 19 Z9 19 U1 0 U2 1 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 JUL 13 PY 1994 VL 272 IS 2 BP 152 EP 153 DI 10.1001/jama.272.2.152 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NV424 UT WOS:A1994NV42400020 PM 8015130 ER PT J AU BENMANSOUR, S BRUNSWICK, DJ AF BENMANSOUR, S BRUNSWICK, DJ TI THE MAO-B INHIBITOR DEPRENYL, BUT NOT THE MAO-A INHIBITOR CLORGYLINE, POTENTIATES THE NEUROTOXICITY OF P-CHLOROAMPHETAMINE SO BRAIN RESEARCH LA English DT Article DE P-CHLOROAMPHETAMINE; NEUROTOXICITY; SEROTONIN UPTAKE SITE; MONOAMINE OXIDASE; PARGYLINE; DEPRENYL; CLORGYLINE ID MONOAMINE-OXIDASE INHIBITORS; RAT-BRAIN; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; EXTRACELLULAR 5-HYDROXYTRYPTAMINE; SEROTONIN; DOPAMINE; METABOLISM; RELEASE; METHYLENEDIOXYMETHAMPHETAMINE; 5,6-DIHYDROXYTRYPTAMINE AB The effect of co-administration of MAO inhibitors together with a low dose of the neurotoxic amphetamine p-chloroamphetamine (pCA) on neurotoxicity was examined. Neurotoxicity was assessed by measuring decreases in the binding of [H-3]cyanoimipramine to serotonin uptake sites using quantitative autoradiography. By itself, a low dose of pCA (2 mg/kg) did not produce any alterations in radioligand binding, measured 7 days after drug administration. However, co-administration of the MAO-B selective inhibitor deprenyl (1 mg/kg) or the non-selective inhibitor pargyline (50 mg/kg) produced significant decreases in radioligand binding. Measurements of the effects of these drugs on body temperature ruled out the possibility that deprenyl and pargyline were increasing neurotoxicity by producing a drug-induced hyperthermia. In contrast to the effects of deprenyl and pargyline, co-administration of the MAO-A selective inhibitor clorgyline (1 mg/kg) did not alter binding. By themselves none of the MAO inhibitors produced neurotoxic effects. There are a number of possible explanations for these results. Administration of deprenyl or pargyline, together with pCA, itself a MAO-A inhibitor, will lead to inhibition of both MAO-A and MAO-B activities. This will likely lead to an enhanced release of dopamine and serotonin compared with the release following administration of pCA alone or pCA together with clorgyline. Elevation of the extracellular levels of either or both of these monoamines could lead to enhanced neurotoxicity. Whatever the mechanism involved, our results show that the co-administration of a type-B MAOI enhances the neurotoxic effects of pCA on serotonin neurons. C1 UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,NEUROPSYCHOPHARMACOL UNIT,PHILADELPHIA,PA 19104. FU NIDA NIH HHS [DA05137] NR 45 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 11 PY 1994 VL 650 IS 2 BP 305 EP 312 DI 10.1016/0006-8993(94)91796-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NW229 UT WOS:A1994NW22900015 PM 7953696 ER PT J AU MAYFIELD, C EBBINGHAUS, S GEE, J JONES, D RODU, B SQUIBB, M MILLER, D AF MAYFIELD, C EBBINGHAUS, S GEE, J JONES, D RODU, B SQUIBB, M MILLER, D TI TRIPLEX FORMATION BY THE HUMAN HA-RAS PROMOTER INHIBITS SP1 BINDING AND IN-VITRO TRANSCRIPTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIHYDROFOLATE-REDUCTASE PROMOTER; PROTO-ONCOGENE PROMOTER; C-MYC PROMOTER; HELIX FORMATION; DNA; OLIGONUCLEOTIDES; SEQUENCE; OLIGODEOXYNUCLEOTIDES; CLEAVAGE; INVITRO AB The central role of the ras oncogenes in the pathogenesis of a wide variety of human malignancies is well established. Toward developing specific transcriptional inhibitors of the human Ha-ras oncogene, we have designed oligonucleotides to target a region of the Ha-ras promoter (-8 to -28) which contains two of the three Sp1 binding sites essential for transcriptional activity. Gel mobility analysis and DNase I footprinting demonstrate that an oligonucleotide (HR21ap) forms a sequence-specific triple helix with its target site in an antiparallel orientation with respect to the purine-rich duplex strand through predominantly G*G:C triplets. Within the Ha-ras promoter, HR21ap binds exclusively to the proximal target Sp1 sites over a similar nontarget distal sequence which, like the target, contains a consensus Sp1 site. Protein binding assays demonstrate that triplex formation by HR21ap inhibits Sp1 binding to the Ha-ras promoter. Moreover, oligonucleotide-directed triplex formation arrests Ha-ras promoter-dependent transcription in vitro, The results presented here suggest that tripler formation by the Ha-ras promoter targeted oligonucleotide may provide a means to specifically inhibit transcription of this oncogene in vivo. C1 UNIV ALABAMA, DEPT BIOCHEM, BIRMINGHAM, AL 35294 USA. UNIV ALABAMA, CTR COMPREHENS CANC, DEPT ORAL PATHOL, BIRMINGHAM, AL 35294 USA. BIRMINGHAM VET AFFAIRS MED CTR, BIRMINGHAM, AL 35294 USA. RP MAYFIELD, C (reprint author), UNIV ALABAMA, DEPT MED, BOLDEN LAB, BIRMINGHAM, AL 35294 USA. FU NCI NIH HHS [R01 CA42664, R01 CA42337, NCI-CN-25428-33] NR 34 TC 59 Z9 60 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 8 PY 1994 VL 269 IS 27 BP 18232 EP 18238 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV422 UT WOS:A1994NV42200070 PM 8027084 ER PT J AU ROSOWSKY, A BADER, H WRIGHT, JE KEYOMARSI, K MATHERLY, LH AF ROSOWSKY, A BADER, H WRIGHT, JE KEYOMARSI, K MATHERLY, LH TI SIDE-CHAIN MODIFIED 5-DEAZAFOLATE AND 5-DEAZATETRAHYDROFOLATE ANALOGS AS MAMMALIAN FOLYPOLYGLUTAMATE SYNTHETASE AND GYLCINAMIDE RIBONUCLEOTIDE FORMYLTRANSFERASE INHIBITORS - SYNTHESIS AND IN-VITRO BIOLOGICAL EVALUATION .48. SYNTHESIS AND BIOLOGICAL-ACTIVITY OF N-OMEGA-HEMIPHTHALOYL-ALPHA,OMEGA-DIAMINOALKANOIC ACID ANALOGS OF AMINOPTERIN AND 3',5-DICHLOROAMINOPTERIN SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; HUMAN-LEUKEMIC CELLS; METHOTREXATE ANALOGS; CCRF-CEM; DIHYDROFOLATE-REDUCTASE; ANTITUMOR-ACTIVITY; CYTO-TOXICITY; RESISTANCE; INVITRO; GLUTAMATE AB Analogues of N-alpha-(4-amino-4-deoxypteroyl)-N-delta-(hemiphthaloyl)-L-ornithine (PT523) with 3',5'-dichloro substitution in the p-aminobenzoyl moiety or with one less or one more CH2 group in the amino acid moiety were synthesized and tested as inhibitors of dihydrofolate reductase (DHFR) activity and cell growth. Replacement of L-ornithine in PT523 by L-2,4-diaminobutanoic acid or L-lysine did not decrease binding to human recombinant DHFR but resulted in some loss of activity against SCC25 human and SCC VII murine squamous cell carcinoma and against MCF-7 human breast carcinoma in culture. PT523 was several times more potent than methotrexate (MTX), aminopterin (AMT), or trimetrexate (TMQ). 3',5'-Dichloro substitution did not decrease either DHFR binding or cytotoxicity. A new synthetic route to PT523 from 2,4-diamino-6-(hydroxymethyl)pteridine and methyl N-alpha-(4-aminobenzoyl)-N-delta-phthaloyl-L-ornithinate was investigated but was not found superior to previously described methods. In comparative experiments on the ability of PT523 and MTX to competitively inhibit the influx of (GR)-5,10-dideazatetrahydrofolate (DDATHF, lometrexol), used here as a surrogate for MTX and reduced folates, the K-i of PT523 was lower than that of MTX in both wild-type CCRF-CEM human leukemic lymphoblasts and the transport- and polyglutamylation-defective subline CEM/MTX. The CCRF-CEM cells were 10-fold more sensitive to PT523 than to MTX, whereas the CEM/MTX cells were 240-fold more sensitive. However, in contrast to other MTX-resistant cells where collateral sensitivity to PT523 has been seen. CEM/MTX cells still showed substantial cross resistance to PT523 which may reflect an unusual heightened ability to utilize exogenous folic acid. The good correlation observed with both cell lines between the cytotoxicity of PT523 and MTX and the ability to inhibit DDATHF influx supported the view that PT523 and MTX share, at least in part, a common protein carrier for membrane transport. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MICHIGAN CANC FDN,DEV THERAPEUT PROGRAM,DETROIT,MI 48201. RP ROSOWSKY, A (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [R01-CA25394, P01-CA19589, R01-CA53535] NR 39 TC 26 Z9 26 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUL 8 PY 1994 VL 37 IS 14 BP 2167 EP 2174 DI 10.1021/jm00040a008 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA NW321 UT WOS:A1994NW32100008 PM 8035423 ER PT J AU YAMADA, T AHNEN, D ALPERS, DH GREENBERG, HB GRAY, L JOSCELYN, KB KAUFFMAN, G PODOLSKY, DK RAY, WA SCHABERG, D SILVERSTEIN, FE SIVAK, MV WILLIAMS, ALB YOLKEN, R AF YAMADA, T AHNEN, D ALPERS, DH GREENBERG, HB GRAY, L JOSCELYN, KB KAUFFMAN, G PODOLSKY, DK RAY, WA SCHABERG, D SILVERSTEIN, FE SIVAK, MV WILLIAMS, ALB YOLKEN, R TI HELICOBACTER-PYLORI IN PEPTIC-ULCER DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB The National Institutes of Health Consensus Development Conference on Helicobacter pylori in Peptic Ulcer Disease brought together specialists in gastroenterology, surgery, infectious diseases, epidemiology, and pathology, as well as the public to address the following questions: (1) What is the causal relationship of H pylori to upper gastrointestinal disease? (2) How does one diagnose and eradicate H pylori infection? (3) Does eradication of H pylori infection benefit the patient with peptic ulcer disease? (4) What is the relationship between H pylori infection and gastric malignancy? (5) Which H pylori-infected patients should be treated? (6) What are the most important questions that must be addressed by future research in H pylori infections? Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the consensus panel concluded that (1) ulcer patients with H pylori infection require treatment with antimicrobial agents in addition to antisecretory drugs whether on first presentation with the illness or on recurrence; (2) the value of treating of nonulcerative dyspepsia patients with H pylori infection remains to be determined; and (3) the interesting relationship between H pylori infection and gastric cancers, requires further exploration. C1 UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,ANN ARBOR,MI 48109. DENVER MED CTR,DENVER,CO. WASHINGTON UNIV,SCH MED,DEPT MED,DIV GASTROINTESTINAL,ST LOUIS,MO 63110. STANFORD UNIV,SCH MED,DEPT MED,DIV GASTROENTEROL,STANFORD,CA 94305. JOSCELYN MCNAIR & JEFFREY PC,ANN ARBOR,MI. MILTON S HERSHEY MED CTR,DEPT SURG,DIV GEN SURG,HERSHEY,PA. MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. VANDERBILT UNIV,SCH MED,DEPT PREVENT MED,NASHVILLE,TN 37212. UNIV TENNESSEE,COLL MED,DEPT MED,MEMPHIS,TN. UNIV WASHINGTON,SCH MED,DIV GASTROENTEROL,SEATTLE,WA. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. UNIV CLEVELAND HOSP,DIV GASTROENTEROL,CLEVELAND,OH 44106. GEORGE WASHINGTON UNIV,MED CTR,DIV GASTROENTEROL,WASHINGTON,DC 20037. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NR 0 TC 1273 Z9 1292 U1 4 U2 37 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 JUL 6 PY 1994 VL 272 IS 1 BP 65 EP 69 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA NU485 UT WOS:A1994NU48500032 ER PT J AU BUBLEY, GJ TEICHER, BA OGATA, GK SANDOVAL, LS KUSUMOTO, T AF BUBLEY, GJ TEICHER, BA OGATA, GK SANDOVAL, LS KUSUMOTO, T TI DIFFERENCES IN IN-VIVO AND IN-VITRO SEQUENCE-SPECIFIC SITES OF CISPLATIN-DNA ADDUCT FORMATION AND DETECTION OF A DOSE-RESPONSE RELATIONSHIP SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE CISPLATIN; ADDUCT FORMATION; PROSTATE CELLS; TAQ POLYMERASE ID ANTITUMOR DRUG CIS-DIAMMINEDICHLOROPLATINUM(II); SINGLE-STRANDED-DNA; HUMAN-CELLS; POLYMERASE; CHROMATIN; INVITRO; PROTEIN; DAMAGE; ALPHA; IDENTIFICATION AB The cytotoxic and mutagenic properties of the anticancer drug cis-diamminedichloroplatinum(II) (cisplatin) are mediated by bifunctional adducts between purines. Experiments performed in this study employed a new repetitive thermal-cycling technique to detect cisplatin adduct formation following exposure of cells in culture (in vivo) or following treatment of purified DNA (in vitro exposure). The initial goal of this study was to determine if cisplatin-DNA adduct formation could be measured accurately using phosphorimaging over a broad concentration range. If this proved possible, it would then be feasible to determine if adduct formation differed within chromatin compared with purified DNA. There were no significant differences in the cisplatin-DNA adduct pattern induced in closed circular or linear double-stranded plasmids in vitro, suggesting that this type of tertiary structural change does not affect the formation of adduct sites. Sequence-specific DNA adduct formation within a human repetitive DNA target sequence, alphoid DNA following cisplatin treatment of prostate cancer cells in culture (in vivo) and treatment of purified DNA in vitro revealed consistent increases in adduct formation over a broad concentration range, validating the experimental technique. Comparing preferences for cisplatin adduct site formation under these different conditions of exposure demonstrated statistically significant differences. Similar differences were detected for cisplatin repair-deficient Xeroderma pigmentosum cells treated in cell culture, indicating that in vivo/in vitro preferences for adduct site formation are not the result of DNA repair in vivo. C1 BETH ISRAEL HOSP,DIV ONCOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [R29-CA51438, R01-CA 50174] NR 31 TC 12 Z9 12 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 5 PY 1994 VL 48 IS 1 BP 145 EP 153 DI 10.1016/0006-2952(94)90234-8 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NZ078 UT WOS:A1994NZ07800019 PM 8043016 ER PT J AU BOTFIELD, MC JANCSO, A WEISS, MA AF BOTFIELD, MC JANCSO, A WEISS, MA TI AN INVARIANT ASPARAGINE IN THE POU-SPECIFIC HOMEODOMAIN REGULATES THE SPECIFICITY OF THE OCT-2 POU MOTIF SO BIOCHEMISTRY LA English DT Article ID REPRESSOR-OPERATOR INTERACTIONS; CATABOLITE GENE ACTIVATOR; DNA-BINDING PROTEINS; LAMBDA-REPRESSOR; TRANSCRIPTION FACTOR; CRYSTAL-STRUCTURE; LAC REPRESSOR; IMMUNOGLOBULIN GENES; SECONDARY STRUCTURE; CRO REPRESSOR AB The homeodomain defines a family of transcription factors broadly involved in the regulation of gene expression. DNA recognition, as observed in three representative complexes (Engrailed, Antennapedia, and MAT alpha 2), is mediated in the major groove by a helix-turn-helix (HTH) element and in the minor groove by an N-terminal arm. The three complexes share similar overall features, but they also exhibit significant differences in DNA interactions. Because these differences may distinguish the biological activities of different classes of homeodomains, we have investigated the contribution of the Oct-2 POU-specific homeodomain (POUHD) to the specificity of the bipartite POU motif. Comparative studies of variant protein-DNA complexes demonstrate the following. (i) Mutations in an invariant residue in the POUHD HTH (N347; residue 10 of the putative recognition alpha-helix) reduce octamer binding with the relaxation of specificity at one position (5'-ATGCAAAT). The inferred HTH side chain-base interaction, although not observed in the solution structure of the Antennapedia complex, is in accord with homologous contacts in the Engrailed and MAT alpha 2 cocrystal structures. (ii) Comparison of the DNA-binding properties of POU and POUHD demonstrates that POUS and POUHD independently regulate specificity at opposite ends of the DNA site (5'TATGCAAAT). Both domains contact the two central bases (5'-TATGCAAAT) where coordinate binding of POUS in the major groove overrides the intrinsic specificity of POUHD in the minor groove. (iii) The differential sensitivity of POU and POUHD to 2'-deoxyinosine substitutions (a minor-groove modification) suggests that POUS binding repositions the POUHD N-terminal ''arm''. Such repositioning is likely to be mediated indirectly through the DNA structure. The existence of alternative POUHD arm binding sites would be in accord with the differences between minor-groove binding sites observed in Engrailed and MAT alpha 2 cocrystal structures. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. FU NIGMS NIH HHS [GM45290] NR 59 TC 9 Z9 9 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 5 PY 1994 VL 33 IS 26 BP 8113 EP 8121 DI 10.1021/bi00192a016 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV423 UT WOS:A1994NV42300016 PM 7912957 ER PT J AU BAHRAM, S BRESNAHAN, M GERAGHTY, DE SPIES, T AF BAHRAM, S BRESNAHAN, M GERAGHTY, DE SPIES, T TI A 2ND LINEAGE OF MAMMALIAN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HLA-B; LYMPHOCYTES-T; MOUSE; ANTIGEN; MHC; ORGANIZATION; EVOLUTION; RECEPTOR; FAMILY; RECOGNITION AB Major histocompatibility complex (MHC) class I genes typically encode polymorphic peptide-binding chains which are ubiquitously expressed and mediate the recognition of intracellular antigens by cytotoxic T cells. They constitute diverse gene families in different species and include the numerous so-called nonclassical genes in the mouse H-2 complex, of which some have been adapted to variously modified functions. We have identified a distinct family of five related sequences in the human MHC which are distantly homologous to class I chains. These MIC genes (MHC class I chain related genes) evolved in parallel with the human class I genes and with those of most if not all mammalian orders. The MICA gene in this family is located near HLA-B and is by far the most divergent mammalian MHC class I gene known. It is further distinguished by its unusual exon-intron organization and preferential expression in fibroblasts and epithelial cells. However, the presence of diagnostic residues in the MICA amino acid sequence translated from cDNA suggests that the putative MICA chain folds similarly to typical class I chains and may have the capacity to bind peptide or other short ligands. These results define a second lineage of evolutionarily conserved MHC class I genes. This implies that MICA and possibly other members in this family have been selected for specialized functions that are either ancient or derived from those of typical MHC class I genes, in analogy to some of the nonclassical mouse H-2 genes. C1 FRED HUTCHINSON CANC RES CTR,HUMAN IMMUNOL PROGRAM,SEATTLE,WA 98104. RP BAHRAM, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI30581, AI31873] NR 35 TC 588 Z9 624 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6259 EP 6263 DI 10.1073/pnas.91.14.6259 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000004 PM 8022771 ER PT J AU CAMPBELL, KS OGRIS, E BURKE, B SU, W AUGER, KR DRUKER, BJ SCHAFFHAUSEN, BS ROBERTS, TM PALLAS, DC AF CAMPBELL, KS OGRIS, E BURKE, B SU, W AUGER, KR DRUKER, BJ SCHAFFHAUSEN, BS ROBERTS, TM PALLAS, DC TI POLYOMA MIDDLE TUMOR-ANTIGEN INTERACTS WITH SHC PROTEIN VIA THE NPTY (ASN-PRO-THR-TYR) MOTIF IN MIDDLE TUMOR-ANTIGEN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PHOSPHATIDYLINOSITOL KINASE-ACTIVITY; GROWTH-FACTOR RECEPTOR; T-ANTIGEN; RECOMBINANT RETROVIRUSES; MEDIATED TRANSFORMATION; SIGNAL TRANSDUCTION; DELETION MUTANTS; TYROSINE KINASES; VIRUS; ASSOCIATION AB Polyomavirus middle tumor antigen (MT) transforms a large number of cell types by binding to and modulating the activities of cellular proteins. Previous genetic analysis defined in MT an independent motif, NPTY (Asn-Pro-Thr-Tyr), required for transformation. This report demonstrates that NPTY is required for interaction between MT and SHC protein, a Src homology 2 (SH2)-containing protooncogene product implicated in activating Ras via association with GRB2 protein. SHC is phosphorylated on tyrosine and associates with GRB2 in MT-transformed cells. These effects require an intact NPTY motif in MT. SHC immunoprecipitates from MT-transformed cells possess kinase activity that phosphorylates not only SHC and MT but also the 85-kDa subunit of phosphatidylinositol 3-kinase. This result suggests that a complex exists that contains, at a minimum, MT, Src family tyrosine kinases, phosphatidylinositol 3-kinase, and SHC. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL & MOLEC BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. FU NCI NIH HHS [CA30002, CA34722, CA57327, R01 CA057327] NR 54 TC 149 Z9 152 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6344 EP 6348 DI 10.1073/pnas.91.14.6344 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000022 PM 8022784 ER PT J AU TSAI, JC PERRELLA, MA YOSHIZUMI, M HSIEH, CM HABER, E SCHLEGEL, R LEE, ME AF TSAI, JC PERRELLA, MA YOSHIZUMI, M HSIEH, CM HABER, E SCHLEGEL, R LEE, ME TI PROMOTION OF VASCULAR SMOOTH-MUSCLE CELL-GROWTH BY HOMOCYSTEINE - A LINK TO ATHEROSCLEROSIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA SYNTHESIS; CELL CYCLE; CYCLIN; ENDOTHELIAL CELLS ID INDEPENDENT RISK FACTOR; PLASMA HOMOCYST(E)INE; MYOCARDIAL-INFARCTION; ENDOTHELIAL-CELLS; ANGIOTENSIN-II; ARTERIAL; DISEASE; CYCLINS; GENE AB Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the growth of both vascular smooth muscle cells and endothelial cells at concentrations similar to those observed in clinical studies. As little as 0.1 mM homocysteine caused a 25% increase in DNA synthesis, and homocysteine at 1 mM increased DNA synthesis by 4.5-fold in rat aortic smooth muscle cells (RASMC). In contrast, homocysteine caused a dose-dependent decrease in DNA synthesis in human umbilical vein endothelial cells. Homocysteine increased mRNA levels of cyclin D1 and cyclin A in RASMC by 3- and 15-fold, respectively, indicating that homocysteine induced the mRNA of cyclins important for the reentry of quiescent RASMC into the cell cycle. Furthermore, homocysteine promoted proliferation of quiescent RASMC, an effect markedly amplified by 2% serum. The growth-promoting effect of homocysteine on vascular smooth muscle cells, together with its inhibitory effect on endothelial cell growth, represents an important mechanism to explain homocysteine-induced atherosclerosis. C1 HARVARD UNIV,SCH PUBL HLTH,CARDIOVASC BIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT MOLEC & CELLULAR TOXICOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. NR 28 TC 626 Z9 684 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6369 EP 6373 DI 10.1073/pnas.91.14.6369 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000027 PM 8022789 ER PT J AU CASTILLO, L SANCHEZ, M CHAPMAN, TE AJAMI, A BURKE, JF YOUNG, VR AF CASTILLO, L SANCHEZ, M CHAPMAN, TE AJAMI, A BURKE, JF YOUNG, VR TI THE PLASMA FLUX AND OXIDATION RATE OF ORNITHINE ADAPTIVELY DECLINE WITH RESTRICTED ARGININE INTAKE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CITRULLINE; DIET; DEGRADATION; ADULTS ID DIETARY ARGININE; METABOLISM AB We hypothesized recently that arginine homeostasis is achieved in humans largely by modulating the rate of arginine degradation. We have tested this hypothesis further by measuring in vivo the whole body rate of conversion of arginine to ornithine and ornithine oxidation in six healthy young adults. Subjects received for 6 days an L-amino acid-based diet supplying an arginine-rich or arginine-free intake and on day 7, following an overnight fast, an 8-h tracer protocol (first 3 h, fast state; next 5 h, fed state) was conducted; L-[guanidino-N-15(2); 5,5-H-2]arginine and L-[5-C-13]ornithine were given as primed, constant intravenous tracers; measurements of the abundances of various isotopologs of arginine, ornithine, and citrulline in plasma were made, and from these the various kinetic parameters of the metabolism of these amino acids were derived. Arginine and ornithine fluxes were significantly (P < 0.001) reduced in the fed state with arginine-free feeding. The rates of conversion (mu mol.kg(-1).h(-1); mean +/- SD) of plasma arginine to ornithine for arginine rich were 12.9 +/- 2.6 and 24.7 +/- 4.8 for fast and fed states. These values were 11.1 +/- 3.5 and 9.6 +/- 1.2 (P > 0.05 and P < 0.001), respectively, with an arginine-free diet. [C-13]Ornithine oxidation was reduced (P < 0.001) by 46% during the fed state when the arginine-free diet was given. The findings strengthen our hypothesis that homeostasis of arginine metabolism in the human host depends importantly upon a regulation in the rate of arginine degradation with, perhaps, little involvement in the de novo net rate of arginine synthesis. C1 MIT,HUMAN NUTR LAB,CAMBRIDGE,MA 02142. MIT,CLIN RES CTR,CAMBRIDGE,MA 02142. SHRINERS BURN INST,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. TRACER TECHNOL INC,SOMERVILLE,MA 02145. FU NCRR NIH HHS [RR88]; NIDDK NIH HHS [DK 15856] NR 18 TC 51 Z9 51 U1 2 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6393 EP 6397 DI 10.1073/pnas.91.14.6393 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000032 PM 8022794 ER PT J AU KOYASU, S TSE, AGD MOINGEON, P HUSSEY, RE MILDONIAN, A HANNISIAN, J CLAYTON, LK REINHERZ, EL AF KOYASU, S TSE, AGD MOINGEON, P HUSSEY, RE MILDONIAN, A HANNISIAN, J CLAYTON, LK REINHERZ, EL TI DELINEATION OF A T-CELL ACTIVATION MOTIF REQUIRED FOR BINDING OF PROTEIN-TYROSINE KINASES CONTAINING TANDEM SH2 DOMAINS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T CELL RECEPTOR; PROTEIN-PROTEIN INTERACTION; INTERLEUKIN 2; CALCIUM; CROSS-LINKING ID RECEPTOR ZETA-CHAIN; AFFINITY PHOSPHOTYROSYL PEPTIDE; SRC HOMOLOGY-2 DOMAIN; ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; CYTOPLASMIC DOMAIN; PHOSPHORYLATION; COMPLEX; TAIL AB To define the T-cell receptor signal transduction moth, we have transfected human and murine T-cell lines with a chimeric receptor consisting of the extracellular and transmembrane domains of human CD8 alpha and the membrane-proximal portion of CD3 xi containing at its C terminus either an 18-amino acid segment (NQLYNELNLGRREEYDVL) or alanine-scanning point mutant derivatives. Crosslinking of the extracellular domain of the chimera is sufficient to initiate Ca2+ flux, interleukin 2 production, and tyrosine phosphorylation of cellular proteins including the chimera. Subsequently, the chimera becomes associated with several tyrosine-phosphorylated proteins, among them the 70-kDa protein tyrosine kinase ZAP70. Mutational data identify the T-cell activation moth as Y(X)(2)L(X)(7)Y(X)(2)L and show that each of the four designated residues is necessary for the above activation events. Recom binant protein containing the two tandem SH2 domains derived from ZAP70 binds to a synthetic peptide corresponding to the above 18-amino acid motif but only when both tyrosines are phosphorylated; in contrast, little or no binding is observed to monophosphorylated or nonphosphorylated analogues. These results imply that after receptor crosslinking in T cells, and by inference also in B cells and mast cells, the motif is phosphorylated on both tyrosine residues, thereafter serving as a docking site for protein tyrosine kinases containing tandem SH2 domains. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RP KOYASU, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,44 BINNEY ST,BOSTON,MA 02115, USA. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [AI19807] NR 45 TC 70 Z9 70 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6693 EP 6697 DI 10.1073/pnas.91.14.6693 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000093 PM 7517560 ER PT J AU YAMASHITA, T BARBER, DL ZHU, Y WU, N DANDREA, AD AF YAMASHITA, T BARBER, DL ZHU, Y WU, N DANDREA, AD TI THE FANCONI-ANEMIA POLYPEPTIDE FACC IS LOCALIZED TO THE CYTOPLASM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MITOMYCIN C; LEUKEMIA SUSCEPTIBILITY ID GROUP-C GENE; MUTATION; CELLS; SUSCEPTIBILITY; BREAKAGE; PROTEINS; CLONING; PRODUCT; REPAIR; REGION AB Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and chromosomal instability. A cDNA encoding the FA complementation group C (FACC) polypeptide was recently cloned [Strathdee, C. A., Gavish, H., Shannon, W. R. and Buchwald, M. (1992) Nature (London) 356, 763-767]. To further characterize this polypeptide, we generated a rabbit polyclonal antiserum against its carboxyl terminus. We used this antiserum to analyze the FACC polypeptide from normal or mutant (FA) lymphoblast cell lines. By immunoprecipitation, the wild-type FACC was a 60-kDa protein, consistent with its predicted molecular mass. FA group C cell lines expressed full-length FACC, truncated FACC, or no detectable FACC polypeptide. In addition, the antiserum specifically immuno precipitated a 50-kDa and a 150-kDa FACC-related protein (FRP-50 and FRP-150). Unexpectedly, cell fractionation and immunofluorescence studies demonstrated that the FACC polypeptide localizes to the cytoplasm. In conclusion, we have generated an antiserum specific for the human FACC polypeptide. The antiserum should be useful for screening FA cells for mutant FACC polypeptides and for identifying and cloning FACC-related proteins. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. NR 27 TC 119 Z9 120 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 1994 VL 91 IS 14 BP 6712 EP 6716 DI 10.1073/pnas.91.14.6712 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NV420 UT WOS:A1994NV42000097 PM 7517562 ER PT J AU WEST, HL REBECK, GW HYMAN, BT AF WEST, HL REBECK, GW HYMAN, BT TI FREQUENCY OF THE APOLIPOPROTEIN-E EPSILON-2 ALLELE IS DIMINISHED IN SPORADIC ALZHEIMER-DISEASE SO NEUROSCIENCE LETTERS LA English DT Article DE APOLIPOPROTEIN E GENE; ALLELE FREQUENCY; ALZHEIMERS DISEASE ID E POLYMORPHISM; TYPE-4 ALLELE; RECEPTOR; BINDING; PROTEIN AB Recent data have demonstrated genetic disequilibrium between inheritance of the apolipoprotein E (apoE) epsilon 4 allele and increased risk of Alzheimer disease. We tested the idea that inheritance of other allelic variations of apoE might also increase or decrease the risk of developing Alzheimer disease. We studied apoE genotypes in a large clinic based population of Alzheimer disease patients and age-compatible, tested control individuals. We confirm the genetic disequilibrium between apoE epsilon 4 and Alzheimer disease and now report that inheritance of apoE epsilon 2, another common variant of the apolipoprotein E gene, is negatively associated with risk of developing Alzheimer disease. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02214. FU NIA NIH HHS [AG08487, 2P50AG05134] NR 20 TC 95 Z9 98 U1 3 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 4 PY 1994 VL 175 IS 1-2 BP 46 EP 48 DI 10.1016/0304-3940(94)91074-X PG 3 WC Neurosciences SC Neurosciences & Neurology GA NW038 UT WOS:A1994NW03800012 PM 7970208 ER PT J AU THOMPSON, BT COCKRILL, BA AF THOMPSON, BT COCKRILL, BA TI RENAL-DOSE DOPAMINE - A SIREN SONG SO LANCET LA English DT Editorial Material ID BLOOD-FLOW; SHOCK RP THOMPSON, BT (reprint author), MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA, USA. NR 12 TC 74 Z9 74 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 JUL 2 PY 1994 VL 344 IS 8914 BP 7 EP 8 DI 10.1016/S0140-6736(94)91044-8 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NU917 UT WOS:A1994NU91700007 PM 7912346 ER PT J AU ROGOWSKA, J PRESTON, K ARONEN, HJ WOLF, GL AF ROGOWSKA, J PRESTON, K ARONEN, HJ WOLF, GL TI A COMPARATIVE-ANALYSIS OF SIMILARITY MAPPING AND EIGENIMAGING AS APPLIED TO DYNAMIC MR-IMAGING OF A LOW-GRADE ASTROCYTOMA SO ACTA RADIOLOGICA LA English DT Article DE MR, CORRELATION; IMAGE SEGMENTATION; IMAGE PROCESSING; ASTROCYTOMA AB This paper compares the abilities of similarity mapping and eigenimaging for the purpose of identifying (segmenting) different image structures in dynamic MR imaging. As an illustrative example a case of dynamic images with a low grade astrocytoma was chosen. It was found that the similarity mapping was more successful than eigenimaging in determining the extent and position of a low grade astrocytoma. Also, similarity mapping was able to identify another region with a different and uncorrelated temporal pattern that was later diagnosed as a cyst. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR NMR,DEPT RADIOL,BOSTON,MA 02114. KENSAL CORP,TUCSON,AZ. RP ROGOWSKA, J (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,DEPT RADIOL,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 9 TC 11 Z9 11 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PD JUL PY 1994 VL 35 IS 4 BP 371 EP 377 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NV286 UT WOS:A1994NV28600012 PM 8011388 ER PT J AU MELAMED, J STONE, B BEAUCHER, WN AF MELAMED, J STONE, B BEAUCHER, WN TI SPONTANEOUS CEREBROSPINAL-FLUID RHINORRHEA WITH ASSOCIATED SINUSITIS AND ALLERGIC RHINITIS SO ALLERGY PROCEEDINGS LA English DT Article AB The entity of spontaneous cerebrospinal fluid rhinorrhea is a rare condition that presents a special challenge to the practicing allergist. Delayed diagnosis can be associated with significant morbity and mortality. We describe two cases of this condition occurring in association with allergic rhinitis and sinusitis. The presentation and management of these cases is described. A high index of suspicion for this condition should be maintained in all patients who present with profuse and often unilateral rhinorrhea. C1 MASSACHUSETTS GEN HOSP,DIV CLIN IMMUNOL,BOSTON,MA 02114. NR 0 TC 3 Z9 3 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD JUL-AUG PY 1994 VL 15 IS 4 BP 197 EP 200 DI 10.2500/108854194778702829 PG 4 WC Allergy SC Allergy GA PE526 UT WOS:A1994PE52600004 PM 7806076 ER PT J AU WANG, SJ SHOHAT, T VADHEIM, C SHELLOW, W EDWARDS, J ROTTER, JI AF WANG, SJ SHOHAT, T VADHEIM, C SHELLOW, W EDWARDS, J ROTTER, JI TI INCREASED RISK FOR TYPE-I (INSULIN-DEPENDENT) DIABETES IN RELATIVES OF PATIENTS WITH ALOPECIA-AREATA (AA) SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE ALOPECIA AREATA; IMMUNOLOGICAL DISEASE; TYPE 1 DIABETES; TYPE 2 DIABETES ID AUTOIMMUNITY; MELLITUS; PREVALENCE; JUVENILE; DISEASE; IDDM AB The prevalence of various chronic diseases was compared in 517 individuals with alopecia areata, and 2,969 of their first degree relatives. As previous reports have suggested an increased incidence of diabetes in relatives of patients with alopecia areata, special attention was given to the prevalence of Type 1 and Type 2 diabetes in the patients and in their relatives. Several immunologic diseases were increased in alopecia probands and relatives. Thyroid disease, vitiligo, Addison disease, and pernicious anemia were more prevalent in probands and in their relatives than in the general population. Specifically, a high rate of thyroid disease was found in probands (14.7%) and in their first degree relatives (4.2%). Only one proband had Type I diabetes, yet there were 14 sibs with Type 1 diabetes. Thus, Type 1 diabetes was significantly more prevalent in the sibs (1.2%) than in either the probands with alopecia (0.2%), or the general population (0.12-0.25%) (P < 0.05)). In contrast, Type 2 diabetes was not more common in probands or in sibs than in the general population. These data suggest that alopecia areata protects against Type 1 diabetes in predisposed individuals. The high rate of thyroid disease suggests that screening probands and first degree relatives for thyroid disease should be considered. (C) 1994 Wiley-Liss, Inc. C1 CEDARS SINAI MED CTR,DEPT MED,DIV MED GENET,CTR MED GENET BIRTH DEFECTS,LOS ANGELES,CA 90048. CEDARS SINAI MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,W LOS ANGELES VET ADM MED CTR,SCH MED,DEPT DERMATOL,LOS ANGELES,CA. HAIR,ALOPECIA AREATA RES FDN,RALEIGH,NC. NR 41 TC 44 Z9 47 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 JUL 1 PY 1994 VL 51 IS 3 BP 234 EP 239 DI 10.1002/ajmg.1320510313 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA NR121 UT WOS:A1994NR12100012 PM 8074151 ER PT J AU BROMLEY, B MANDELL, J GROSS, G WALZER, TB BENACERRAF, BR AF BROMLEY, B MANDELL, J GROSS, G WALZER, TB BENACERRAF, BR TI MASCULINIZATION OF FEMALE FETUSES WITH CONGENITAL ADRENAL-HYPERPLASIA MAY ALREADY BE PRESENT AT 18 WEEKS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Note DE CONGENITAL ADRENAL HYPERPLASIA; MASCULINIZATION ID DIAGNOSIS AB We report a case of virilization of twin female fetuses because of congenital adrenal hyperplasia ultrasonographically evident at 18 weeks. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,DIV UROL,BOSTON,MA 02115. NR 2 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 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1994 VL 171 IS 1 BP 264 EP 265 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NZ068 UT WOS:A1994NZ06800044 PM 8030711 ER PT J AU YANG, WI ZUKERBERG, LR MOTOKURA, T ARNOLD, A HARRIS, NL AF YANG, WI ZUKERBERG, LR MOTOKURA, T ARNOLD, A HARRIS, NL TI CYCLIN D1 (BCL-1, PRAD1) PROTEIN EXPRESSION IN LOW-GRADE B-CELL LYMPHOMAS AND REACTIVE HYPERPLASIA SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INTERMEDIATE LYMPHOCYTIC LYMPHOMA; NON-HODGKINS-LYMPHOMAS; MANTLE-ZONE LYMPHOMA; CENTROCYTIC LYMPHOMA; MOLECULAR-CLONING; CHROMOSOME-TRANSLOCATION; RETINOBLASTOMA PROTEIN; CANDIDATE ONCOGENE; PUTATIVE ONCOGENE; PRAD1/CYCLIN D1 AB Mantle cell (centrocytic) lymphoma (MCL) and occasional cases of B-cell small lymphocytic lymphoma/chronic lymphocytic leukemia (B-SLL/ CLL) show a characteristic translocation, t(11:14)(q13;q32) involving rearrangement of the Bcl-1 region Recently it was shown that the key Bcl-1-region oncogene is cyclic D1/PRAD1; cyclin D1 mRNA was shown to be overexpressed in cases of MCL. We examined cyclin DI protein expression is low-grade B-cell lymphomas and reactive lymphoid hyperplasias using polyclonal and monoclonal antibodies to cyclin D1 protein. Definite nuclear staining was seen ia 15 of 15 MCLs, 1 of 7 B-SLL/CLLs, 0 of 7 reactive hyperplasias, 0 of 10 follicular lymphomas, and 0 of 4 lymphomas of mucosa-associated lymphoid tissue using immunoperoxidase stains on paraffin-embedded sections. Best results were obtained with the affinity-purified polyclonal antibody on microwave-treated, formalin-fixed, paraffin-embedded tissue, MCLs showed diffuse nuclear staining, whereas the one positive B-SLL/CLL showed dot-like or globular nuclear staining. Nuclear cyclin DI protein can be detected in all cases of MCL and in rare cases of B-SLL/CLL using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue, and it does not appear to be detectable in reactive hyperplasias and other low-grade and cell lymphomas. This protein may be useful in subclassification of low-grade B-cell lymphomas. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,ENDOCRINE ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA55909, 5F32CA09260-2] NR 51 TC 169 Z9 172 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 JUL PY 1994 VL 145 IS 1 BP 86 EP 96 PG 11 WC Pathology SC Pathology GA NV861 UT WOS:A1994NV86100014 PM 7518196 ER PT J AU EHRLICH, HP DESMOULIERE, A DIEGELMANN, RF COHEN, IK COMPTON, CC GARNER, WL KAPANCI, Y GABBIANI, G AF EHRLICH, HP DESMOULIERE, A DIEGELMANN, RF COHEN, IK COMPTON, CC GARNER, WL KAPANCI, Y GABBIANI, G TI MORPHOLOGICAL AND IMMUNOCHEMICAL DIFFERENCES BETWEEN KELOID AND HYPERTROPHIC SCAR SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SMOOTH MUSCLE ACTIN; GRANULATION-TISSUE; MONOCLONAL-ANTIBODY; ELECTRON-MICROSCOPE; MYOFIBROBLASTS; IMMUNOFLUORESCENCE; CONTRACTION; FIBRONECTIN; FIBROBLASTS; EXPRESSION AB There are two types of excessive scarring, keloid and hypertrophic scar. Contrary to hypertrophic scars, keloids do not regress with time, are difficult to revise surgically, and do not provoke scar contractures. These two lesions require different therapeutic approaches but are often confused because of an apparent lack of morphological differences. We have investigated the collagen organization and the possible presence of alpha-smooth muscle (SM) actin-expressing myofibroblasts in these conditions. Keloids contain large, thick collagen fibers composed of numerous fibrils closely packed together. In contrast hypertrophic scars exhibit nodular structures in which fibroblastic cells, small vessels, and fine, randomly organized collagen fibers are present. We confirm that such nodular structures are at ways present in hypertrophic scar and rarely in keloid. Furthermore, only nodules of hypertrophic scars contain alpha-SM actin-expressing myofibroblasts. Electron microscopic examination supports the above-mentioned differences in collagen organization and in fibroblastic features and shows the presence of an amorphous extracellular material surrounding fibroblastic cells in keloid. The presence in hypertrophic scar myofibroblasts of alpha-SM actin, the actin isoform typical of vascular SM cells, may represent an important element in the pathogenesis of contraction. Interestingly, when placed in culture fibroblasts from hypertrophic scars and keloids express similar amounts of alpha-SM actin, suggesting that local microenvironmental factors influence in vivo the expression of this protein. Thus several morphological and immunohistochemical differences exist between hypertrophic scar and keloid that are useful for the biological and pathological characterization of the two lesions. C1 UNIV GENEVA,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT SURG,HERSHEY,PA 17033. VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DIV PLAST & RECONSTRUCT SURG,RICHMOND,VA. MASSACHUSETTS GEN HOSP,SHRINERS BURNS INST,DEPT PATHOL,BOSTON,MA 02114. UNIV MICHIGAN,CTR MED,CTR BURN,ANN ARBOR,MI 48109. INST PASTEUR,CNRS,URA 1459,LYON,FRANCE. NR 31 TC 310 Z9 328 U1 2 U2 11 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 JUL PY 1994 VL 145 IS 1 BP 105 EP 113 PG 9 WC Pathology SC Pathology GA NV861 UT WOS:A1994NV86100016 PM 8030742 ER PT J AU SCHWIEBERT, EM GESEK, F ERCOLANI, L WJASOW, C GRUENERT, DC KARLSON, K STANTON, BA AF SCHWIEBERT, EM GESEK, F ERCOLANI, L WJASOW, C GRUENERT, DC KARLSON, K STANTON, BA TI HETEROTRIMERIC G-PROTEINS, VESICLE TRAFFICKING, AND CFTR CL- CHANNELS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE EXOCYTOSIS; CYSTIC FIBROSIS ID EPITHELIAL-CELL LINE; GTP-BINDING PROTEINS; CYSTIC-FIBROSIS; BREFELDIN-A; KINASE-A; TRANSPORT; SECRETION; PHOSPHORYLATION; CONDUCTANCES; G-ALPHA-I-3 AB Previously (E. M. Schwiebert, N. Kizer, D. C. Gruenert, and B. A. Stanton. Proc. Natl. Acad. Sci. USA 89: 10623-10627, 1992), we showed that heterotrimeric G proteins regulate adenosine 3',5'-cyclic monophosphate (cAMP)-activated cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels in human airway epithelial cells. The goal of the present study was to test the hypothesis that heterotrimeric G proteins regulate vesicle trafficking and exocytosis and that these events are critical for cAMP activation of CFTR-mediated Cl- secretion. We report that cAMP stimulates exocytosis and CFTR Cl- conductance (G(Cl)) in normal but not in CF cells. Stimulation of the heterotrimeric G protein G alpha(i-2) inhibited cAMP-activated CFTR G(Cl) and exocytosis in normal cells. In contrast, inhibition of G alpha(i-2) stimulated exocytosis and allowed cAMP to stimulate CFTR G(Cl) in cells isolated from patients with cystic fibrosis (CF). Brefeldin A and nocodazol prevented cAMP-induced exocytosis and also blocked cAMP stimulation of CFTR G(Cl) in normal airway epithelial cells. Our studies suggest that the heterotrimeric G protein G alpha(i-2) regulates CFTR G(Cl) in human airway epithelial cells by modulating vesicle trafficking and the delivery of CFTR Cl- channels from an intracellular vesicular pool to the plasma membrane. Inhibition of G alpha(i-2) may be a useful therapeutic approach to target mutant Delta F508 CFTR Cl- channels from an intracellular vesicular pool to the plasma membrane and thereby correct defective Cl- secretion in CF airway epithelial cells. C1 DARTMOUTH COLL, SCH MED, DEPT PHYSIOL, HANOVER, NH 03755 USA. DARTMOUTH COLL, SCH MED, DEPT PHARMACOL, HANOVER, NH 03755 USA. MASSACHUSETTS GEN HOSP, RENAL UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. UNIV CALIF SAN FRANCISCO, CARDIOVASC RES INST, SAN FRANCISCO, CA 94143 USA. FU NIDDK NIH HHS [DK-45881] NR 33 TC 71 Z9 72 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1994 VL 267 IS 1 BP C272 EP C281 PN 1 PG 10 WC Physiology SC Physiology GA NY984 UT WOS:A1994NY98400030 PM 7519398 ER PT J AU LEVITSKY, LL ZHENG, QJ MINK, K RHOADS, DB AF LEVITSKY, LL ZHENG, QJ MINK, K RHOADS, DB TI GLUT-1 AND GLUT-2 MESSENGER-RNA, PROTEIN, AND GLUCOSE-TRANSPORTER ACTIVITY IN CULTURED FETAL AND ADULT HEPATOCYTES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE GLUCOSE PHOSPHORYLATION; FETAL HEPATOCYTE GLYCOGENESIS ID RAT HEPATOCYTES; DIFFERENTIAL REGULATION; EXPRESSION; LIVER; CLONING; CELLS; BETA AB To understand glycogenesis in the fetal hepatocyte, we examined glucose transport in cultured fetal and adult male rat hepatocytes. GLUT-1 mRNA was detected in fetal hepatocytes at isolation but in adult hepatocytes only after culture. GLUT-1 mRNA was more abundant in fetal than in adult hepatocytes (P < 0.005). GLUT-1 protein paralleled its message. GLUT-2 mRNA was more abundant in adult than in fetal hepatocytes (P < 0.05), and abundance did not change during culture, but GLUT-2 protein was discordantly regulated. There was more GLUT-2 protein in fetal hepatocytes at 45 h (P < 0.025). An Eadie-Hofstee plot of 3-O-methylglucose transport appeared to have two linear components. One component was presumed to be GLUT-1 [variable Michaelis constant (K-m) approximating 6-8 mM, maximal uptake rate (V-max) for fetal vs. adult hepatocytes 106 vs. 35 nmol.min(-1).mg protein(-1)], and a second was presumed to be GLUT-2 (K-m of 23 mM, V-max for fetal vs. adult hepatocytes 198 vs. 92 nmol.min(-1).mg protein(-1)). Early phosphorylation of 2-deoxyglucose was greater in fetal than in adult hepatocytes, but transport was always greater than phosphorylation. Increased expression of both GLUT-1 and GLUT-2 by fetal hepatocytes permits greater glucose uptake and positions the fetal rat hepatocyte for efficient glycogenesis at low plasma glucose concentration. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP LEVITSKY, LL (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,CHILDRENS SERV & LAB TUMOR BIOL,PEDIAT ENDOCRINE UNIT,BOSTON,MA 02114, USA. FU NICHD NIH HHS [HD-22891]; NIDDK NIH HHS [DK-01392-34] NR 20 TC 18 Z9 18 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 JUL PY 1994 VL 267 IS 1 BP E88 EP E94 PN 1 PG 7 WC Physiology SC Physiology GA NY984 UT WOS:A1994NY98400046 PM 8048518 ER PT J AU HAJJAR, RJ INGWALL, JS GWATHMEY, JK AF HAJJAR, RJ INGWALL, JS GWATHMEY, JK TI MECHANISM OF ACTION OF 2,3-BUTANEDIONE MONOXIME ON CONTRACTURE DURING METABOLIC INHIBITION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SKINNED FIBERS; RIGOR; ADENOSINE 5'-TRIPHOSPHATE; CREATINE PHOSPHATE; CROSS BRIDGES ID NUCLEAR-MAGNETIC-RESONANCE; FERRET VENTRICULAR MUSCLE; INTRACELLULAR CALCIUM; DYNAMIC STIFFNESS; SKELETAL-MUSCLE; ATPASE ACTIVITY; RAT; HEART; ISCHEMIA; MYOCYTES AB The effect of 2,3-butanedione monoxime (BDM) was investigated during metabolic inhibition (MI) in papillary muscles. MI caused a rapid decrease in developed force and an increase in resting force, along with a decrease in ATP and creatine phosphate (CrP). Addition of BDM before MI decreased maximal contracture force, increased the time, and slowed the rates of ATP and CrP depletion. BDM addition at the peak of contracture did not alter the level of developed contracture. To simulate MI in skinned fiber preparations, we decreased the [MgATP] at pCa 8. [MgATP] of 3.2 mu M resulted in a large increase in resting force. The force developed was less in BDM-pretreated muscles. Addition of 10 mM BDM at steady state did not affect force development ([MgATP] 3.2 mu M, pCa 8.0). Cross-bridge kinetics in intact and skinned muscle fibers with and without BDM in the presence and absence of MI were studied. Intact muscles with MI revealed no frequency dependence at peak contracture and had elevated stiffness values. In skinned fibers, at [MgATP] of 3.2 mu M and pCa of 8, no frequency dependence was observed, and the muscles had similarly high stiffness values. BDM pretreatment in both intact and skinned fibers inhibited rigor formation. These results suggest that BDM inhibits cross-bridge formation in the weak-binding state or actively cycling cross bridges. C1 HARVARD UNIV, CHARLES A DANA RES INST, CARDIOVASC DIS & MUSCLE RES LABS, BOSTON, MA 02115 USA. HARVARD UNIV, BETH ISRAEL HOSP, DEPT CELLULAR & MOLEC PHYSIOL, THORNDIKE LABS, BOSTON, MA 02215 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BOSTON, MA 02114 USA. FU NHLBI NIH HHS [HL-39091, HL-36797] NR 40 TC 12 Z9 12 U1 2 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1994 VL 267 IS 1 BP H100 EP H108 PN 2 PG 9 WC Physiology SC Physiology GA NY985 UT WOS:A1994NY98500013 PM 8048573 ER PT J AU WAKABAYASHI, G CANNON, JG GELFAND, JA CLARK, BD AIURA, K BURKE, JF WOLFF, SM DINARELLO, CA AF WAKABAYASHI, G CANNON, JG GELFAND, JA CLARK, BD AIURA, K BURKE, JF WOLFF, SM DINARELLO, CA TI ALTERED INTERLEUKIN-1 AND TUMOR-NECROSIS-FACTOR PRODUCTION AND SECRETION DURING PYROGENIC TOLERANCE TO LPS IN RABBITS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE FEVER; CYTOKINES; MONONUCLEAR CELL; RABBIT; PROTEIN SYNTHESIS; SECRETION ID BLOOD MONONUCLEAR-CELLS; EARLY ENDOTOXIN TOLERANCE; RECEPTOR ANTAGONIST; ESCHERICHIA-COLI; IL-1; CACHECTIN; SHOCK; TNF; TRANSCRIPTION; EXPRESSION AB Rabbits were injected intravenously with 10 mu g/kg of endotoxin [lipopolysaccharide (LPS)] on days 0, 1, and 7, and rectal temperatures were monitored. The febrile responses were compared with circulating levels of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) and in vitro synthesis of these cytokines by peripheral blood mononuclear cells (PBMC) isolated just before the injection of LPS. Fever after the first LPS injection was biphasic on day 0, attenuated and monophasic after the second LPS injection on day 1, and augmented after third injection of LPS on day 7. On day 1, circulating TNF and IL-1 beta levels were significantly (P < 0.05) decreased compared with those on days 0 and 7. Similarly, TNF and IL-1 beta synthesis by LPS-stimulated PBMC were significantly reduced on day 1. On day 7, cellular synthesis and secretion of IL-1 beta were significantly increased compared with that on day 0. A significant positive correlation was observed between fever index and total in vitro IL-1 beta synthesis by LPS-stimulated PBMC (r = 0.866, P = 0.001). These data demonstrate that pyrogenic tolerance in the rabbit after a single LPS injection is associated with decreased circulating IL-1 beta and TNF levels as well as decreased production of these cytokines in vitro. In addition, the pyrogenic hyperresponsiveness to LPS after 7 days is associated with increased synthesis and secretion of IL-1 beta from PBMC in vitro. C1 TUFTS UNIV NEW ENGLAND MED CTR,DIV GEOG MED & INFECT DIS,BOSTON,MA 02111. TUFTS UNIV,DEPT MED,DIV GEOG MED & INFECT DIS,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NIAID NIH HHS [AI-15614]; NIAMS NIH HHS [AR-39595]; NIGMS NIH HHS [GM-21700] NR 37 TC 17 Z9 17 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 JUL PY 1994 VL 267 IS 1 BP R329 EP R336 PN 2 PG 8 WC Physiology SC Physiology GA NY985 UT WOS:A1994NY98500095 PM 8048640 ER PT J AU NIERENBERG, AA ADLER, LA PESELOW, E ZORNBERG, G ROSENTHAL, M AF NIERENBERG, AA ADLER, LA PESELOW, E ZORNBERG, G ROSENTHAL, M TI TRAZODONE FOR ANTIDEPRESSANT-ASSOCIATED INSOMNIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SLEEP; FLUOXETINE; INHIBITOR AB Objective: The authors investigated trazodone as a hypnotic for depressed patients who had persistent, exacerbated, or new insomnia while taking either fluoxetine or bupropion. Method: Seventeen depressed patients who had insomnia while taking fluoxetine or bupropion were given either trazodone or placebo in a double-blind crossover trial. Sleep was assessed by self-report with the Pittsburgh Sleep Quality Index and the sleep items of the Yale-New Haven Hospital Depressive Symptom Inventory. Results: Improvement with trazodone, but not with placebo, was shown by the total Pittsburgh index scores and Yale-New Haven inventory total sleep scores and by the Pittsburgh index measures of sleep duration and Yale-New Haven inventory measures of early morning awakening, and there was a trend toward improvement in the Yale-New Haven inventory item regarding middle of the night awakenings. Subjective sleep quality and sleep latency also showed a trend toward improvement, but the Pittsburgh index measures of sleep efficiency and disturbances and the Yale-New Haven inventory item regarding difficulty falling asleep were unaffected by trazodone. One patient dropped out because of excessive daytime sedation with trazodone, and another dropped out because of nonresponse to placebo. Of the completers, 67% experienced overall improvement in sleep with trazodone according to a priori criteria, whereas only 13% experienced improvement with placebo. Conclusions: Trazodone is an effective hypnotic for patients with antidepressant-associated insomnia. C1 DEPT VET AFFAIRS,PSYCHIAT SERV,NEW YORK,NY. NYU,SCH MED,DEPT PSYCHIAT,NEW YORK,NY. MCLEAN HOSP,DEPT PSYCHIAT,AFFECT DISORDERS PROGRAM,BELMONT,MA 02178. RP NIERENBERG, AA (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,WACC-815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 17 TC 136 Z9 146 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 1994 VL 151 IS 7 BP 1069 EP 1072 PG 4 WC Psychiatry SC Psychiatry GA NU656 UT WOS:A1994NU65600020 PM 8010365 ER PT J AU LAFER, B SACHS, GS LABBATE, LA THIBAULT, A ROSENBAUM, JF AF LAFER, B SACHS, GS LABBATE, LA THIBAULT, A ROSENBAUM, JF TI PHOTOTHERAPY FOR SEASONAL AFFECTIVE-DISORDER - A BLIND COMPARISON OF 3 DIFFERENT SCHEDULES SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID LIGHT; ANTIDEPRESSANT AB The authors investigated the outcome of an alternating time schedule versus two fixed schedules (either morning or evening) of bright light treatment for seasonal affective disorder. The subjects were 31 patients who met DSM-III-R criteria for major depression with a seasonal pattern. No statistically significant difference was observed among patients in the three groups for response criteria after 1 week of treatment. These results support the use of more flexible phototherapy schedules. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP LAFER, B (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,ACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 8 TC 17 Z9 17 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 1994 VL 151 IS 7 BP 1081 EP 1083 PG 3 WC Psychiatry SC Psychiatry GA NU656 UT WOS:A1994NU65600025 PM 8010369 ER PT J AU THRALL, JH AF THRALL, JH TI THE RADIOLOGIST IN THE 1990S - NEW PRACTICE EXPECTATIONS AND MANAGEMENT RESPONSIBILITIES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB Radiology has enjoyed an enviable position among medical specialties during the past two decades. Unprecedented developments in new technology expanded its horizons, and the volume of radiologic procedures increased far more than overall growth in health care services. The attendant increase in relative and absolute health care spending on radiologic services has cast radiology as a prime target for restrictions, cutbacks, and limitations in an era of managed care and national concern for reining in the growth of health care spending. A strategic response by radiologists requires an understanding of the implications of structural change in health care delivery systems and payment systems. To meet the imperatives of the 1990s, radiologists must do far more than perform and interpret imaging procedures: they must learn to work as efficient managers of health care imaging resources and to organize their practices for effective contracting and service delivery for patients in managed care systems. RP THRALL, JH (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,55 FRUIT ST,BOSTON,MA 02114, USA. NR 0 TC 21 Z9 21 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1994 VL 163 IS 1 BP 11 EP 15 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE286 UT WOS:A1994QE28600003 PM 8010194 ER PT J AU KAUFMAN, JA GELLER, SC PETERSEN, MJ CAMBRIA, RP PRINCE, MR WALTMAN, AC AF KAUFMAN, JA GELLER, SC PETERSEN, MJ CAMBRIA, RP PRINCE, MR WALTMAN, AC TI MR-IMAGING (INCLUDING MR-ANGIOGRAPHY) OF ABDOMINAL AORTIC-ANEURYSMS - COMPARISON WITH CONVENTIONAL ANGIOGRAPHY SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MAGNETIC-RESONANCE ANGIOGRAPHY; PREOPERATIVE EVALUATION; OCCLUSIVE DISEASE; RENAL-ARTERIES; AORTOGRAPHY; REPAIR; CT AB OBJECTIVE. The purpose of this report is to compare the results of MR imaging, including MR angiography, with the results of conventional angiography in the imaging of abdominal aortic aneurysms (AAA). SUBJECTS AND METHODS. Twenty seven nonconsecutive patients with known AAA underwent both MR imaging (including MR angiography) and conventional angiography preoperatively. MR imaging was done before angiography according to the following protocol in all patients: sagittal and coronal Tf-weighted images of the abdomen, followed by axial MR angiograms obtained with a multiple overlapping thin-slab acquisition (MOTSA) three-dimensional time-of-flight (3D TOF) volume centered on the renal arteries. Last, coronal MR angiograms were obtained with a dynamic contrast-enhanced 3D TOF volume centered on the aorta. Conventional angiography was subsequently performed in all patients. Data from each study were collected prospectively and analyzed in a blinded manner. For the MR studies, all sequences were used to determine the extent of the AAA and the presence of iliac aneurysms; stenotic disease of the celiac, superior mesenteric, renal, and iliac arteries and the number and location of renal arteries were determined from the MR angiograms. For evaluation of the extent of the aneurysm, results from both techniques were compared with surgical results; otherwise MR angiography was compared with conventional angiography, Confidence intervals for sensitivity and specificity were calculated at the 95% level, The McNemar test was used for comparison of proportions. RESULTS, MR angiography had a sensitivity of 100% (4/4) and a specificity of 91% (21/23) for the four stenoses of the celiac artery that were greater than 50%. For detection of renal artery stenoses of greater than 50%, present in nine arteries, the sensitivity was 89% (8/9) and specificity was 98% (49/50). MR angiography showed 100% (54/54) of all main renal arteries and 78% (7/9) of all accessory renal arteries seen on conventional angiograms. The proximal extent of the aneurysm was correctly predicted on the basis of MR findings in 100% (26/26) of patients with surgical correlation, compared with 92% (24/26) when conventional angiograms were used. This difference was not statistically significant (p > .1). MR imaging had a sensitivity of 100% (19/19) for detection of isolated aneurysms of the common iliac artery, and MR angiography had a 100% sensitivity (5/5) and specificity (103/103) for detection of stenoses greater than 50% in the common and external iliac arteries. One circumaortic left renal vein was visualized on MR images. CONCLUSION. These results suggest that MR angiography may be a useful noninvasive method of determining the presence of coexistent celiac, superior mesenteric, renal, and iliac atherosclerotic disease in patients with AAA. C1 MASSACHUSETTS GEN HOSP,DIV VASC SURG,GEN SURG SERV,BOSTON,MA 02114. RP KAUFMAN, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. RI Prince, Martin/S-6850-2016 NR 29 TC 76 Z9 78 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUL PY 1994 VL 163 IS 1 BP 203 EP 210 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE286 UT WOS:A1994QE28600043 PM 8010215 ER PT J AU CHEW, FS PALMER, WE AF CHEW, FS PALMER, WE TI INTERACTIVE ATLAS OF JOINT ANATOMY ON MR-IMAGES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB We designed and developed an atlas of joint anatomy based on MR images. Using a workstation that consisted of a computer and a videodisc player, each with its own monitor, the program presented complete sets of labeled MR images of the joints by using a variety of common pulse sequences in standard imaging planes. The images were stored on videodisc and were retrieved and displayed under the control of the computer program. The images could be viewed in a self-paced, structured sequence or in any arbitrary, self-directed way. Interactive features included a quiz mode that challenged the user to name the anatomic structures, one at a time. The atlas has been exhibited at national meetings and currently is used in our residency and fellowship training programs. 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. OI Chew, Felix/0000-0003-2711-2013 NR 4 TC 4 Z9 4 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 JUL PY 1994 VL 163 IS 1 BP 211 EP 213 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA QE286 UT WOS:A1994QE28600044 PM 8010216 ER PT J AU VACANTI, CA KIM, WS SCHLOO, B UPTON, J VACANTI, JP AF VACANTI, CA KIM, WS SCHLOO, B UPTON, J VACANTI, JP TI JOINT RESURFACING WITH CARTILAGE GROWN IN-SITU FROM CELL-POLYMER STRUCTURES SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article AB We tested the potential of a new technology developed in our laboratory to create new hyaline cartilage for resurfacing distal femoral joint surfaces of New Zealand White rabbits that had been surgically denuded of articular cartilage. We removed hyaline cartilage from the patellar groove of the distal femurs in 24 rabbits. Chondrocytes isolated from the excised cartilage of 12 of these rabbits (experimentals) were seeded onto synthetic biocompatible, biodegradable polymers composed of polyglycolic acid. The cells were labeled in vitro with a thymidine analog, BrdU (5-bromo-2'-deoxyuridine). After 1 week in vitro, the cell-polymer structures were implanted onto the denuded surfaces of 12 defects made in the hyaline cartilage of the contralateral knees of the experimental animals. Twelve control animals received either no implants or implants not containing cells on similar surgical defects. After 7 weeks, we found evidence of new cartilage growth in 11 of the 12 experimental animals and virtually no new cartilage formation in any of the animals in either control group. Immunohistochemical analysis demonstrated the presence of BrdU-labeled chondrocytes in representative specimens. RP VACANTI, CA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANASTHESIOL,WHITE 5,BOSTON,MA 02114, USA. NR 0 TC 105 Z9 108 U1 0 U2 2 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD JUL-AUG PY 1994 VL 22 IS 4 BP 485 EP 488 DI 10.1177/036354659402200408 PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA NX453 UT WOS:A1994NX45300010 PM 7943513 ER PT J AU BAYES, J SLATER, EM HEDBERG, PS LAWSON, D AF BAYES, J SLATER, EM HEDBERG, PS LAWSON, D TI OBSTRUCTION OF A DOUBLE-LUMEN ENDOTRACHEAL-TUBE BY A SABER-SHEATH TRACHEA SO ANESTHESIA AND ANALGESIA LA English DT Note C1 N SHORE MED CTR,DEPT THORAC & VASC SURG,SALEM,MA. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. RP BAYES, J (reprint author), N SHORE MED CTR,DEPT ANESTHESIA,81 HIGHLAND AVE,SALEM,MA 01970, USA. NR 8 TC 14 Z9 14 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 1994 VL 79 IS 1 BP 186 EP 188 PG 3 WC Anesthesiology SC Anesthesiology GA NU612 UT WOS:A1994NU61200036 PM 8010435 ER PT J AU TISHER, CC BASTL, CP BISTRIAN, BR CHESNEY, R COGGINS, C DIENERWEST, M FANESTIL, DD GRANTHAM, J KUNAU, R LUKE, RG MADISON, SL MARTINEZMALDONADO, M SALICK, R AF TISHER, CC BASTL, CP BISTRIAN, BR CHESNEY, R COGGINS, C DIENERWEST, M FANESTIL, DD GRANTHAM, J KUNAU, R LUKE, RG MADISON, SL MARTINEZMALDONADO, M SALICK, R TI MORBIDITY AND MORTALITY OF RENAL DIALYSIS - AN NIH CONSENSUS CONFERENCE STATEMENT SO ANNALS OF INTERNAL MEDICINE LA English DT Article AB The National Institutes of Health Consensus Development Conference on Morbidity and Mortality of Dialysis brought together experts in general medicine, nephrology, pediatrics, biostatistics, and nutrition, as well as a representative of the public, to address the following question: 1) How does early medical intervention in predialysis patients influence morbidity/mortality? 2) What is the relationship between delivered dialysis dose and morbidity/mortality? 3) Can comorbid conditions be altered by nondialytic interventions to improve morbidity/mortality in dialysis patients? 5) What are the future directions for research in dialysis? After one and a half days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared their consensus statement. Among their findings, the consensus panel concluded the following: 1) During the period before dialysis therapy begins, patients, including children, should be referred to a renal team to reduce the morbidity and mortality incurred during subsequent dialysis therapy; 2) the social and psychological welfare and the quality of life of the patient receiving dialysis are favorably influenced by the early and continued involvement of a multidisciplinary renal team; 3)to avoid a catastrophic onset of dialysis, attempts should be made to institute intervention before dialysis therapy begins and to appropriately initiate dialysis access; 4) quantitative methods now available to objectively evaluate the relation between the delivered dose of dialysis and patient morbidity and mortality suggest that the dose of hemodialysis and peritoneal dialysis has been suboptimal for many patients in the United States; 5) factors contributing to the underdialysis of some patients include problems with vascular and peritoneal access, nonadherence to dialysis prescription, and underprescription of the dialysis dose; 6) cardiovascular mortality accounts for approximately 50% of deaths in patients receiving dialysis, and relative risk factors such as hypertension, smoking, and chronic anemia should be treated as soon as possible after the diagnosis of chronic renal failure; 7) early detection and treatment of malnutrition contribute to the improved survival of patients receiving dialysis; and 8) until randomized controlled trials have been completed, a delivered hemodialysis dose at least equal to a measured fractional urea clearance K(dr)t/V value of 1.2 (single pool) and a delivered peritoneal dialysis dose at least equal to a measured K(pr)t/V value of 1.7 (weekly) are recommended. C1 TEMPLE UNIV,HLTH SCI CTR,DIV NEPHROL,PHILADELPHIA,PA 19140. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,BOSTON,MA 02215. UNIV TENNESSEE,COLL MED,DEPT PEDIAT,MEMPHIS,TN. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21205. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV KANSAS,MED CTR,DIV NEPHROL & HYPERTENS,KANSAS CITY,KS. DALLAS NEPHROL ASSOCIATES,DALLAS,TX. UNIV CINCINNATI,MED CTR,DEPT MED,CINCINNATI,OH 45267. GEORGE WASHINGTON UNIV,MED CTR,DEPT NURSING,DIV MED SURG,WASHINGTON,DC 20037. EMORY UNIV,SCH MED,DEPT MED,DECATUR,GA 30033. NATL KIDNEY FDN,ORLANDO,FL. RP TISHER, CC (reprint author), UNIV FLORIDA,COLL MED,DIV NEPHROL HYPERTENS & TRANSPLANTAT,GAINESVILLE,FL, USA. NR 0 TC 165 Z9 166 U1 2 U2 5 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 JUL 1 PY 1994 VL 121 IS 1 BP 62 EP 70 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA PN271 UT WOS:A1994PN27100013 ER PT J AU TSUDA, T LOPEZ, R ROGAEVA, EA FREEDMAN, M ROGAEV, E DRACHMAN, D POLLEN, D HAINES, J LIANG, Y MCLACHLAN, DRC DUARA, R STGEORGEHYSLOP, P AF TSUDA, T LOPEZ, R ROGAEVA, EA FREEDMAN, M ROGAEV, E DRACHMAN, D POLLEN, D HAINES, J LIANG, Y MCLACHLAN, DRC DUARA, R STGEORGEHYSLOP, P TI ARE THE ASSOCIATIONS BETWEEN ALZHEIMERS-DISEASE AND POLYMORPHISMS IN THE APOLIPOPROTEIN-E AND THE APOLIPOPROTEIN-CII GENES DUE TO LINKAGE DISEQUILIBRIUM SO ANNALS OF NEUROLOGY LA English DT Note ID TYPE-4 ALLELE; EARLY-ONSET; CHROMOSOME-19; EPSILON-4; DIAGNOSIS; MUTATION; BINDING; LOCUS; RISK AB Allele frequencies for polymorphisms in the apolipoprotein E and the apolipoprotein CII genes were determined in subjects of Ashkenazi Jewish origin with late-onset Alzheimer's disease and in unaffected control subjects from the same ethnic group. A significant association was observed between late-onset Alzheimer's disease and the epsilon 4 (112(Cys-->Arg)) allele of apolipoprotein E; however, no association was detected with apolipoprotein CII. These results suggest that the association with epsilon 4 is probably not due to linkage disequilibrium. C1 UNIV TORONTO,DEPT MED,DIV NEUROL,TORONTO M5S 1A8,ON,CANADA. UNIV TORONTO,CTR RES NEURODEGENERAT DIS,TORONTO M5S 1A8,ON,CANADA. UNIV MIAMI,MT SINAI MED CTR,WEIN CTR ALZHEIMER DIS,MIAMI BEACH,FL 33140. BAYCREST CTR GERIATR CARE,BEHAV NEUROL PROGRAM,TORONTO,ON,CANADA. BAYCREST CTR GERIATR CARE,ROTMAN RES INST,TORONTO,ON,CANADA. UNIV MASSACHUSETTS,MED CTR,DEPT NEUROL,WORCESTER,MA 01655. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MOLEC NEUROGENET UNIT,BOSTON,MA. RUSSIAN ACAD MED SCI,NATL RES CTR MENTAL HLTH,MOSCOW,RUSSIA. MT SINAI HOSP,DEPT MED NEUROL,TORONTO M5G 1X5,ON,CANADA. RI Haines, Jonathan/C-3374-2012; OI Lopez, Ramon/0000-0001-5881-1365 FU NIA NIH HHS [U24 AG021886] NR 27 TC 44 Z9 44 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 JUL PY 1994 VL 36 IS 1 BP 97 EP 100 DI 10.1002/ana.410360118 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NW518 UT WOS:A1994NW51800016 PM 8024269 ER PT J AU CULLEN, DJ APOLONE, G GREENFIELD, S GUADAGNOLI, E CLEARY, P AF CULLEN, DJ APOLONE, G GREENFIELD, S GUADAGNOLI, E CLEARY, P TI ASA PHYSICAL STATUS AND AGE PREDICT MORBIDITY AFTER 3 SURGICAL-PROCEDURES SO ANNALS OF SURGERY LA English DT Article ID COMPLICATIONS; ANESTHESIA; OUTCOMES; MORTALITY AB Objective American Society of Anesthesiologists-Physical Status scores (ASA-FS) and age were used to adjust for case-mix differences when evaluating surgical morbidity and resource use alter total hip replacement (THR), transurethral prostatectomy (TURF), or cholecystectomy. Summary Background Data Variations in complication rates or resource use among patients treated for a particular primary condition should be adjusted for coexistent disease. Age and ASA-PS scores are readily available and can be useful to stratify surgical patients for risk. Methods One thousand ninety patients at five academic medical centers in California and Massachusetts who underwent THR, TURF, or cholecystectomy between 1985 and 1987 were studied. Data were obtained from medical records and a self-administered questionnaire to measure length of stay (LOS), postoperative complication rates, and follow-up physician visits. Data were analyzed with one- and two-way analysis of variance with the Bonferroni correction. Results Increasing age and ASA-FS scores were associated significantly with increased LOS, complication rates, and frequency of post-discharge physician office visits. No interaction effect between age and ASA-PS scores was observed. Conclusions Age and ASA-PS scores can predict postoperative morbidity, specific for each operation studied. Assessment of co-morbidity in surgical patients can be accomplished easily and with minimal expense. While remaining budget neutral, the distribution of reimbursements should be based on those preoperative risk factors that predict longer LOS and higher complication rates. C1 TUFTS UNIV,SCH MED,NEW ENGLAND MED CTR,INST IMPROVEMENT MED CARE & HLTH,MEDFORD,MA 02155. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA 02115. RP CULLEN, DJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ANESTHESIA,BOSTON,MA, USA. RI Apolone, Giovanni/R-9799-2016 OI Apolone, Giovanni/0000-0001-5179-104X NR 24 TC 114 Z9 116 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUL PY 1994 VL 220 IS 1 BP 3 EP 9 DI 10.1097/00000658-199407000-00002 PG 7 WC Surgery SC Surgery GA NU604 UT WOS:A1994NU60400002 PM 8024356 ER PT J AU BARCHIESI, F COLOMBO, AL MCGOUGH, DA FOTHERGILL, AW RINALDI, MG AF BARCHIESI, F COLOMBO, AL MCGOUGH, DA FOTHERGILL, AW RINALDI, MG TI IN-VITRO ACTIVITY OF ITRACONAZOLE AGAINST FLUCONAZOLE-SUSCEPTIBLE AND FLUCONAZOLE-RESISTANT CANDIDA-ALBICANS ISOLATES FROM ORAL CAVITIES OF PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID KETOCONAZOLE; AIDS AB A broth macrodilution technique, which was performed by following the recommendations provided by the National Committee for Clinical Laboratory Standards (document M27-P), was applied to study the in vitro activity of itraconazole against fluconazole-susceptible and -resistant Candida albicans isolates from the oral cavities of 100 patients infected with human immunodeficiency virus. The in vitro data demonstrated that itraconazole had good activity against the tested isolates; for 90% of all strains of C. albicans, MICs were 1 mu g/ml, and only one isolate was highly resistant to this triazole (MIC, >16 mu g/ml). However, the itraconazole MICs for the fluconazole-susceptible isolates were significantly lower than those for the fluconazole-resistant isolates; the MICs for 50 and 90% of the isolates tested were less than or equal to 0.03 and 0.25 mu g/ml, respectively, for the fluconazole-susceptible isolates and 0.5 and 1 mu g/ml, respectively, for the fluconazole-resistant isolates (P = 0.00001). Our findings could be of clinical relevance because human immunodeficiency virus-infected patients who fail fluconazole therapy for oral and/or esophageal candidiasis may require itraconazole at doses higher than those used in standard therapy. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. UNIV ANCONA,IST MALATTIE INFET & MED PUBBL,ANCONA,ITALY. ESCOLA PAULISTA MED,BR-04023 SAO PAULO,BRAZIL. RP BARCHIESI, F (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,FUNGUS TESTING LAB,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 21 TC 86 Z9 89 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 JUL PY 1994 VL 38 IS 7 BP 1530 EP 1533 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NU598 UT WOS:A1994NU59800016 PM 7979284 ER PT J AU ATKINSON, BA BOCANEGRA, R COLOMBO, AL GRAYBILL, JR AF ATKINSON, BA BOCANEGRA, R COLOMBO, AL GRAYBILL, JR TI TREATMENT OF DISSEMINATED TORULOPSIS-GLABRATA INFECTION WITH DO870 AND AMPHOTERICIN-B SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NEUTROPENIC MICE; CANDIDIASIS; MORTALITY AB Torulopsis glabrata, an opportunist pathogen in immunosuppressed patients, is resistant to many antifungal agents, and there are no established treatment regimens for this organism. The mouse model was used to evaluate treatment with DO870, amphotericin B, fluconazole, and their combination. Mice were immunosuppressed with 5 mg of gold sodium thiomalate given intraperitoneally 1 day prior to intravenous infection with 10(8) T. glabrata cells. Treatment with a new antifungal triazole, DO870, at doses ranging from 1 to 50 mg/kg of body weight administered per os either daily or on alternate days; fluconazole at 100 mg/kg twice a day per os; or amphotericin B at 3 mg/kg/day intraperitoneally was begun 1 day after infection. Treatment for 5 days was followed by sacrifice 2 days later for determining CFU counts in spleen and kidney tissue. For a fluconazole-sensitive isolate (MIC of DO870, < 1.25 mu g/ml), DO870 at 5 mg/kg/day significantly reduced counts in kidney and spleen tissue (P < 0.05), amphotericin B was modestly effective, and the combination of DO870 (25 mg/kg) and amphotericin B (3 mg/kg) was markedly more effective than either drug alone (P < 0.01). Three additional isolates were resistant in vitro to DO870 (MIC, 4 mu g/ml). No reduction in CFU in kidney or spleen tissue was observed with DO870 when compared with counts in control tissue. DO870 is effective in vivo against at least some isolates of T. glabrata and when combined with amphotericin B can exert additive effects. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV INFECT DIS,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. ESCOLA PAULISTA MED,BR-04023 SAO PAULO,BRAZIL. NR 19 TC 14 Z9 14 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 JUL PY 1994 VL 38 IS 7 BP 1604 EP 1607 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NU598 UT WOS:A1994NU59800027 PM 7979293 ER PT J AU SHAPIRO, BH PAMPORI, NA LAPENSON, DP WAXMAN, DJ AF SHAPIRO, BH PAMPORI, NA LAPENSON, DP WAXMAN, DJ TI GROWTH HORMONE-DEPENDENT AND HORMONE-INDEPENDENT SEXUALLY DIMORPHIC REGULATION OF PHENOBARBITAL-INDUCED HEPATIC CYTOCHROME-P450-2B1 AND CYTOCHROME-P450-2B2 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID RAT-LIVER; MONOSODIUM GLUTAMATE; ULTRADIAN RHYTHM; GENE-EXPRESSION; FEMALE RATS; SECRETION; FORMS; SUPPRESSION; ENZYMES; PATTERN AB Sexually dimorphic regulation of phenobarbital-induced cytochromes P450 2B1 and 2B2 (collectively referred to as P450 2B) as well as P450 2B-dependent monooxygenase activities was studied in multi-hormone-depleted hypophysectomized rats and in growth hormone (GH)-deficient monosodium glutamate (MSG)-treated rats. Our results indicate that endogenous GH suppresses phenobarbital induction of P450 2B and that the feminine pattern of continuous GH secretion is more suppressive than the masculine profile of episodic secretion. Moreover, we have found that it is the height of the GH pulse, and not necessarily its frequency nor the interpulse trough periods, that signals the suppressive effects of GH on P450 2B expression in male rats. Last, irrespective of the presence or absence of circulating GH, the magnitude of phenobarbital induction of P450 2B and associated monooxygenases was consistently lower in female rats, suggesting the presence of some degree of sex-dependent, but GH-independent regulation. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP SHAPIRO, BH (reprint author), UNIV PENN,SCH VET MED,DEPT ANIM BIOL,BIOCHEM LABS,3800 SPRUCE ST,PHILADELPHIA,PA 19104, USA. FU NICHD NIH HHS [HD-16358]; NIDDK NIH HHS [DK-33765]; NIGMS NIH HHS [GM-45758] NR 41 TC 38 Z9 39 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1994 VL 312 IS 1 BP 234 EP 239 DI 10.1006/abbi.1994.1304 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NX107 UT WOS:A1994NX10700032 PM 8031133 ER PT J AU HAUSER, R GARCIACLOSAS, M KELSEY, KT CHRISTIANI, DC AF HAUSER, R GARCIACLOSAS, M KELSEY, KT CHRISTIANI, DC TI VARIABILITY OF NASAL LAVAGE POLYMORPHONUCLEAR LEUKOCYTE COUNTS IN UNEXPOSED SUBJECTS - ITS POTENTIAL UTILITY FOR EPIDEMIOLOGY SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID BIOLOGIC MARKERS; INFLAMMATION; POLLUTANTS; HUMANS; OZONE AB Recent studies have utilized nasal lavage to study the inflammatory cells of the nasal epithelium. In unexposed subjects, investigators have reported wide interindividual variability in lavage cell counts. The intraindividual variability of cell counts in sequential lavages has been less well described. Investigators have also reported that nasal lavage may washout cells, resulting in lower cell counts on subsequent lavages. The present study was designed to characterize both the variability in cell counts in unexposed volunteers and the kinetics of cell washout. Twenty-one subjects participated in two nasal lavage trials. In Trial 1, a baseline lavage was followed by a lavage 72 h later; in Trial 2, the baseline lavage was followed by a lavage 48 h later. Intraclass correlation coefficients of reliability (R) were calculated for each trial. In Trial 1, the R was 0.88, with a one-sided confidence interval greater than or equal to 0.75, whereas in Trial 2 R was 0.67, with a confidence interval greater than or equal to 0.40. The smaller R in Trial 2 may suggest that washout was more evident at 48 h than at 72 h after the baseline lavage. Furthermore, these R values suggest that within-subject variability is smaller than between-subject variability, supporting the utility of nasal lavage as a reliable technique for investigating the nasal cavity response to air pollutants. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA. RP HAUSER, R (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,665 HUNTINGTON AVE,BOSTON,MA 02115, USA. RI Kelsey, Karl/I-1252-2014; Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU NIEHS NIH HHS [ES00002, ES05947, ES07069] NR 12 TC 24 Z9 24 U1 0 U2 0 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD JUL-AUG PY 1994 VL 49 IS 4 BP 267 EP 272 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA NZ333 UT WOS:A1994NZ33300010 PM 8031183 ER PT J AU TOLLEFSON, GD RAMPEY, AH POTVIN, JH JENIKE, MA RUSH, AJ DOMINGUEZ, RA KORAN, LM SHEAR, MK GOODMAN, W GENDUSO, LA AF TOLLEFSON, GD RAMPEY, AH POTVIN, JH JENIKE, MA RUSH, AJ DOMINGUEZ, RA KORAN, LM SHEAR, MK GOODMAN, W GENDUSO, LA TI A MULTICENTER INVESTIGATION OF FIXED-DOSE FLUOXETINE IN THE TREATMENT OF OBSESSIVE-COMPULSIVE DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID OPEN CLINICAL-TRIAL; DOUBLE-BLIND; CLOMIPRAMINE TREATMENT; SEROTONERGIC RESPONSIVITY; BEHAVIOR-THERAPY; UPTAKE INHIBITOR; FLUVOXAMINE; DESIPRAMINE; SCALE AB Objectives: To determine the effectiveness of fluoxetine hydrochloride at fixed doses of 20 mg/d, 40 mg/d, and 60 mg/d in patients with obsessive-compulsive disorder (OCD) and to evaluate its safety. Methods: Fixed-dose fluoxetine hydrochloride (20 mg/d, 40 mg/d, 60 mg/d) was compared with placebo in two randomized, double-blind, parallel, 13-week trials of identical design in 355 outpatients with OCD aged 15 to 70 years (DSM-III-R criteria; 1 year's duration or longer; depression secondary if present). Results: Fluoxetine (all doses) was significantly (P less than or equal to.001) superior to placebo on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score (mean baseline-to-end-point decrease, 4.6, 5.5, and 6.5 vs 0.9, respectively, studies pooled) and other efficacy measures (P less than or equal to.01). A trend suggesting greater efficacy at 60 mg/d was observed. Most patients (79.2%) completed the study. Eight adverse events were statistically significantly more frequent with fluoxetine and one, with placebo. For some events, incidence tended to increase with increasing dosage; however, few patients discontinued treatment for any single event. Conclusion: Fluoxetine was associated with a statistically significant reduction in OCD severity, including time engaged in obsessional and/or compulsive behaviors. Adverse events infrequently led to study discontinuation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. UNIV TEXAS,SW MED SCH,DEPT PSYCHIAT,DALLAS,TX. UNIV MIAMI,SCH MED,DEPT PSYCHIAT,CORAL GABLES,FL 33124. STANFORD UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,STANFORD,CA. CORNELL UNIV MED COLL,NEW YORK HOSP,DEPT PSYCHIAT,ITHACA,NY. YALE UNIV,SCH MED,CONNECTICUT MENTAL HLTH CTR,NEW HAVEN,CT 06508. RP TOLLEFSON, GD (reprint author), ELI LILLY & CO,LILLY CORP CTR 218,DIV PSYCHOPHARMACOL,INDIANAPOLIS,IN 46285, USA. OI Rush, Augustus/0000-0003-2004-2382 NR 66 TC 236 Z9 239 U1 2 U2 10 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 JUL PY 1994 VL 51 IS 7 BP 559 EP 567 PG 9 WC Psychiatry SC Psychiatry GA NW199 UT WOS:A1994NW19900010 PM 8031229 ER PT J AU AIELLO, LP ARRIGG, PG SHAH, ST MURTHA, TJ AIELLO, LM AF AIELLO, LP ARRIGG, PG SHAH, ST MURTHA, TJ AIELLO, LM TI SOLAR RETINOPATHY ASSOCIATED WITH HYPOGLYCEMIC INSULIN REACTION SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material RP AIELLO, LP (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BEETHAM EYE INST,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 5 TC 0 Z9 0 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 JUL PY 1994 VL 112 IS 7 BP 982 EP 983 PG 2 WC Ophthalmology SC Ophthalmology GA NX187 UT WOS:A1994NX18700031 PM 8031281 ER PT J AU FOITZIK, T BASSI, DG FERNANDEZDELCASTILLO, C WARSHAW, AL RATTNER, DW AF FOITZIK, T BASSI, DG FERNANDEZDELCASTILLO, C WARSHAW, AL RATTNER, DW TI INTRAVENOUS CONTRAST-MEDIUM IMPAIRS OXYGENATION OF THE PANCREAS IN ACUTE NECROTIZING PANCREATITIS IN THE RAT SO ARCHIVES OF SURGERY LA English DT Article ID ENHANCED COMPUTED-TOMOGRAPHY; REFLECTANCE SPECTROPHOTOMETRY; BLOOD-FLOW; TRYPSINOGEN ACTIVATION; INTRINSIC REGULATION; NECROSIS; PERFUSION; MICROCIRCULATION; HEMODYNAMICS; CONSUMPTION AB Objective: Contrast-enhanced computed tomography is widely used to evaluate severe acute necrotizing pancreatitis (ANP) by demonstrating areas of malperfusion, which might indicate irreversible necrosis. Because of our prior finding that the intravenous contrast medium (CM) accentuates the severity of ANP by promoting further necrosis and higher mortality, we sought to investigate the mechanism by which this injury is mediated. Resign: Mild acute pancreatitis was induced in Sprague-Dawley rats with intravenous caerulein hyperstimulation; and severe ANP, with intravenous caerulein plus intraductal glycodeoxycholic acid. Control animals and rats with pancreatitis were randomized to be given intravenous CM or saline. Main Outcome Measure: Diffuse reflectance spectroscopy was used to measure the index of hemoglobin content and oxygen saturation in pancreatic tissues in vivo. Results: Oxygen saturation of hemoglobin was increased in animals with mild acute pancreatitis (AP) (mean [+/-SEM], 58.7% +/- 1.2% vs 55.2% +/- 1.5% in control animals; P<.05) and was decreased in animals with ANP (51.2% +/- 1.2% vs 55.2% +/- 1.5%; P<.05). Fifteen minutes after the infusion of CM, oxygen saturation of hemoglobin significantly decreased further in animals with ANP (51.4% +/- 1.8% before infusion of CM vs 46.1% +/- 1.7% at 15 minutes; P<.05) and remained significantly below the comparable group receiving intravenous saline for the entire 60-minute test. This decrement was not observed in animals with ANP given saline or in animals with mild AP or in control animals after infusion of saline or CM. The index of hemoglobin content remained unchanged throughout the experiment in all groups. Conclusions: The prolonged reduction of oxygen saturation of hemoglobin in the pancreas following the administration of intravenous CM in rats with severe ANP indicates that CM impairs the pancreatic microcirculation in necrotizing forms of AP. This may explain our previous finding that CM increases pancreatic injury and mortality in rodents with ANP, and it underlines our concern that the use of contrast-enhanced computed tomography early in human AP may promote the evolution of pancreatic necrosis. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WANG AMBULATORY CARE CTR 336,BOSTON,MA 02114. NR 50 TC 46 Z9 46 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD JUL PY 1994 VL 129 IS 7 BP 706 EP 711 PG 6 WC Surgery SC Surgery GA NW481 UT WOS:A1994NW48100006 PM 8024450 ER PT J AU BERTHIAUME, F REIKEN, SR TONER, M TOMPKINS, RG YARMUSH, ML AF BERTHIAUME, F REIKEN, SR TONER, M TOMPKINS, RG YARMUSH, ML TI ANTIBODY-TARGETED PHOTOLYSIS OF BACTERIA IN-VIVO SO BIO-TECHNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; HEMATOPORPHYRIN; INVITRO; INFECTION; TOXIN; CELLS AB We have evaluated the efficacy of antibody-targeted photolysis to kill bacteria in vivo using specific antibacterial photosensitizer (PS) immunoconjugates. After infecting the dorsal skin in mice with Pseudomonos aeruginosa, both specific and nonspecific tin (IV) chlorin e(6)-monoclonal antibody conjugates were injected at the infection site. After a 15 min incubation period, the site was exposed to 630 mm light with a power density of 100 mW/cm(2) for 1600 seconds. Irradiation resulted in a greater than 75% decrease in the number of viable bacteria at sites treated with a specific conjugate, whereas normal bacterial growth was observed in animals that were untreated or treated with a nonspecific conjugate. Antibody-targeted photolysis may be a selective and versatile tool for treating a variety of infections. C1 MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114. SHRINERS BURN INST,BOSTON,MA 02114. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. NR 29 TC 63 Z9 67 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD JUL PY 1994 VL 12 IS 7 BP 703 EP 706 DI 10.1038/nbt0794-703 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA NU370 UT WOS:A1994NU37000025 PM 7764916 ER PT J AU ALARCON, C CHEATHAM, B LINCOLN, B KAHN, CR SIDDLE, K RHODES, CJ AF ALARCON, C CHEATHAM, B LINCOLN, B KAHN, CR SIDDLE, K RHODES, CJ TI A KEX2-RELATED ENDOPEPTIDASE ACTIVITY PRESENT IN RAT-LIVER SPECIFICALLY PROCESSES THE INSULIN PRORECEPTOR SO BIOCHEMICAL JOURNAL LA English DT Article ID CONSTITUTIVE SECRETORY PATHWAY; HAMSTER OVARY CELLS; YEAST KEX2 PROTEASE; PROTEOLYTIC CONVERSION; SEQUENCE REQUIREMENTS; PRECURSOR CLEAVAGE; COMPLEMENT PRO-C3; PROTO-ONCOGENE; RECEPTOR CDNA; FURIN AB The insulin proreceptor is cleaved by limited proteolysis posttranslationally at an Arg-Lys-Arg-Arg site to generate its mature alpha- and beta-subunit form. An S-35-labelled insulin proreceptor substrate preparation and a 15-mer peptide substrate that mimics the amino acid sequence around and including the insulin proreceptor processing site (IRP-peptide) has revealed an endopeptidase activity that catalyses insulin proreceptor cleavage in a rat liver subcellular fraction. Under optimal conditions, normal S-35-labelled insulin proreceptor substrate processing by this fraction was quantitative. This fraction was not able to process an S-35-labelled insulin proreceptor variant substrate (where the Arg(-1) of the tetrabasic cleavage site had been replaced by Ala(-1)), similarly to previous in vivo observations, suggesting that this endopeptidase activity has physiological relevance. Biochemical characterization of the insulin proreceptor/IRP-peptide processing revealed this rat liver endopeptidase activity to have a broad pH range (> 70% maximal activity between pH 5.5 and 10.0) and a pH optimum of pH 8-10. It was Ca2+-dependent activity, maximally active between 0.5 and 5 mM Ca2+ and half-maximally activated between 50 and 90 mu M Ca2+. Endoproteolytic activity was not inhibited by group-specific inhibitors of serine-, cysteinyl or aspartyl proteinases or by 1,10-phenanthroline; however, EDTA and 1,2-cyclohexanediaminetetraacetic acid did inhibit the activity, but this was accounted for by Ca2+ chelation. The IRP-peptide substrate assay enabled measurement of an apparent K-m of 22 mu M and a V-max of 18.6 pmol/min for this endopeptidase activity. These biochemical characteristics suggest the insulin proreceptor processing endopeptidase activity to be a legitimate member of the Kex2-related proprotein convertase family. Immunoblotting detected furin and PACE4 proteins (both members of this family) to be present in the rat liver subcellular fraction containing insulin proreceptor processing activity. Since the biochemical characteristics of the insulin proreceptor processing endopeptidase activity mostly resembled those of furin activity, it is likely that insulin proreceptor proteolytic maturation can be catalysed by furin in the liver. C1 BRIGHAM & WOMENS HOSP,JOSLIN DIABET CTR,DIV RES,EP JOSLIN RES LAB,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CAMBRIDGE,ADDENBROOKES HOSP,DEPT CLIN BIOCHEM,CAMBRIDGE CB2 2QR,ENGLAND. FU NIDDK NIH HHS [DK31036, DK36836] NR 56 TC 19 Z9 19 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 1994 VL 301 BP 257 EP 265 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY661 UT WOS:A1994NY66100039 PM 8037679 ER PT J AU LABBATE, LA POLLACK, MH OTTO, MW LANGENAUER, S ROSENBAUM, JF AF LABBATE, LA POLLACK, MH OTTO, MW LANGENAUER, S ROSENBAUM, JF TI SLEEP PANIC ATTACKS - AN ASSOCIATION WITH CHILDHOOD ANXIETY AND ADULT PSYCHOPATHOLOGY SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SLEEP PANIC; PANIC DISORDER; ANXIETY; CHILDHOOD ID BEHAVIORAL-INHIBITION; CLINICAL FINDINGS; DISORDER; CHILDREN AB The authors examine whether the presence of sleep panic attacks identifies a subgroup of panic disorder patients. Subjects (n = 95) were consecutive patients with panic disorder participating in the MGH longitudinal study of panic disorder. Patients were evaluated with structured interviews to establish adult anxiety and affective disorders, and the presence of childhood anxiety disorders. Patients were queried whether they had ever experienced at least one panic attack during sleep. Patients with a history of sleep panic had significantly higher rates of comorbid generalized anxiety disorder (p < 0.01), social phobia (p < 0.03), and major depression (p < 0.005). The trend was toward longer length of illness (p = 0.09) and were more likely to have a history of an anxiety disorder during childhood (p < 0.005). The presence of sleep panic attacks may delineate a subgroup of panic disorder patients with early difficulties with anxiety, and comorbid mood and anxiety disorders as adults. C1 MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. NR 11 TC 19 Z9 19 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 JUL 1 PY 1994 VL 36 IS 1 BP 57 EP 60 DI 10.1016/0006-3223(94)90063-9 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NU182 UT WOS:A1994NU18200008 PM 8080905 ER PT J AU MORGAN, JR LEE, JW TOMPKINS, RG YARMUSH, ML AF MORGAN, JR LEE, JW TOMPKINS, RG YARMUSH, ML TI RAPID QUANTITATION OF RECOMBINANT RETROVIRUSES SO BIOTECHNOLOGY PROGRESS LA English DT Note ID HUMAN-GENE-THERAPY; VECTORS; CELLS; IMPLANTATION; EXPRESSION; LINEAGE; SAFE AB A method for measuring the concentration of recombinant retrovirus encoding the Escherichia coli LacZ gene is described. The assay is based on the quantitative measurement of beta-galactosidase activity in extracts of cells infected with the LacZ-encoding retrovirus. LacZ-encoded beta-galactosidase activity in transduced cells is measured using the colorimetric substrate, o-nitrophenyl beta-D-galactopyranoside (ONPG), and the results are read using an ELISA plate-reader. Because the entire assay is performed in a 96-well plate, large numbers of samples are easily measured, and the assay has the advantages of rapidity, precision, and ease of data collection. The assay was used to determine the optimal concentration of polybrene, a polycation known to enhance the infectivity of retroviruses, and can be used to evaluate other factors that affect infection, as well as the optimal conditions for production of the recombinant retrovirus. C1 SHRINERS BURN INST,BOSTON,MA 02114. RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08854. RP MORGAN, JR (reprint author), MASSACHUSETTS GEN HOSP,TRAUMA SERV,BIGELOW 13,ROOM 1302,BOSTON,MA 02114, USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [P01 HD28528-01] NR 22 TC 14 Z9 14 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JUL-AUG PY 1994 VL 10 IS 4 BP 441 EP 446 DI 10.1021/bp00028a014 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA PC847 UT WOS:A1994PC84700015 PM 7765097 ER PT J AU NEOTE, K MAK, JY KOLAKOWSKI, LF SCHALL, TJ AF NEOTE, K MAK, JY KOLAKOWSKI, LF SCHALL, TJ TI FUNCTIONAL AND BIOCHEMICAL-ANALYSIS OF THE CLONED DUFFY ANTIGEN - IDENTITY WITH THE RED-BLOOD-CELL CHEMOKINE RECEPTOR SO BLOOD LA English DT Note ID HISTAMINE-RELEASING-FACTOR; MONOCYTE CHEMOTACTIC PROTEIN-1; ACTIVATING FACTOR; PLASMODIUM-VIVAX; HUMAN BASOPHILS; MALARIA PARASITE; CYTOKINE; RANTES; CHEMOATTRACTANT; IDENTIFICATION C1 GENENTECH INC, DEPT IMMUNOL, S SAN FRANCISCO, CA 94080 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, RENAL UNIT, BOSTON, MA USA. NR 48 TC 189 Z9 197 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JUL 1 PY 1994 VL 84 IS 1 BP 44 EP 52 PG 9 WC Hematology SC Hematology GA NV959 UT WOS:A1994NV95900007 PM 7517217 ER PT J AU MILLS, BG FRAUSTO, A SINGER, FR OHSAKI, Y DEMULDER, A ROODMAN, GD AF MILLS, BG FRAUSTO, A SINGER, FR OHSAKI, Y DEMULDER, A ROODMAN, GD TI MULTINUCLEATED CELLS FORMED IN-VITRO FROM PAGETS BONE-MARROW EXPRESS VIRAL-ANTIGENS SO BONE LA English DT Article DE PAGETS BONE MARROW; GIANT CELLS IN VITRO; VIRAL ANTIGENS ID DISEASE; CULTURES AB Paget's disease of bone is characterized by large numbers of osteoclasts that have viral-like nuclear and/or cytoplasmic inclusions. Pagetic osteoclasts express respiratory syncytial viral (RSV) and measles viral (MV) nucleocapsid antigens. The data suggest a possible viral etiology for Paget's disease. However, studies to characterize further the putative viral inclusions in Paget's osteoclasts have been severely hampered by the extreme difficulty in isolating large numbers of osteoclasts from pagetic bone. The recent demonstration that osteoclast-like multinucleated cells (MNC), that had certain characteristics of pagetic osteoclasts formed in marrow cultures from Paget's patients, may permit studies to describe this virus further. Therefore, we have cultured marrow samples from involved and uninvolved bones from Paget's patients and from normal subjects to determine if the MNC formed in these cultures express viral antigens. RSV and/or MV antigens were expressed in the mononuclear cells and/or the MNC formed in 12 of 12 marrow cultures from active lesions of patients with Paget's disease, with 40-50% of the cells expressing viral antigens. In contrast, less than 5% of cells isolated from cultures from normal subjects expressed RSV and/or MV. These results suggest that MNC formed in long-term marrow cultures from patients with Paget's disease frequently express paramyxoviral antigens and are very similar to pagetic osteoclasts. Thus, these marrow cultures may be useful for further characterizing the virus in Paget's disease. C1 UNIV SO CALIF,ORTHOPED HOSP,LOS ANGELES,CA. VET ADM MED CTR,SAN ANTONIO,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. CEDARS SINAI MED CTR,LOS ANGELES,CA. RP MILLS, BG (reprint author), ORTHOPED HOSP,2400 S FLOWER ST,LOS ANGELES,CA 90007, USA. FU NCI NIH HHS [CA40035]; NIADDK NIH HHS [AM-19980]; NIAMS NIH HHS [AR-35188] NR 18 TC 46 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 8756-3282 J9 BONE JI Bone PD JUL-AUG PY 1994 VL 15 IS 4 BP 443 EP 448 DI 10.1016/8756-3282(94)90823-0 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NP070 UT WOS:A1994NP07000011 PM 7917585 ER PT J AU IINUMA, S FARSHI, SS ORTEL, B HASAN, T AF IINUMA, S FARSHI, SS ORTEL, B HASAN, T TI A MECHANISTIC STUDY OF CELLULAR PHOTODESTRUCTION WITH 5-AMINOLEVULINIC ACID-INDUCED PORPHYRIN SO BRITISH JOURNAL OF CANCER LA English DT Article ID PHOTODYNAMIC THERAPY; 5-AMINOLEVULINIC ACID; PROTOPORPHYRIN-IX; TUMOR-CELLS; ENDOGENOUS PROTOPORPHYRIN; RAT; PHOTOSENSITIZERS; FLUORESCENCE; CANCER; PHTHALOCYANINE AB 5-Aminolaevulinic acid (ALA)-induced porphyrin biosynthesis and phototoxicity in vitro was investigated in five malignant and two normal cell lines. Intracellular protoporphyrin IX (PpIX) content was quantified by extraction and fluorescence spectroscopy. Cellular PpIX content did not always correlate with cell proliferation rate as measured by the doubling times of cell lines. Cellular efflux of PpIX was also investigated. In a bladder carcinoma cell line, the observed rapid efflux was not blocked by verapamil, an inhibitor of the P-glycoprotein efflux pump. These data support the view that cellular PpIX accumulation is a dynamic process that is determined by both the efflux of PpIX from the cells and enzyme activities in the haem biosynthesis pathway. Desferrioxamine (desferal), a modulator of PpIX biosynthesis, enhanced ALA-induced cellular PpIX content significantly in all carcinoma cell lines but not in non-malignant cell lines. The enhanced PpIX cellular accumulation is attributed to inhibition of ferrochelatase activity, the enzyme responsible for the conversion of PpIX to haem. PpIX-mediated cellular photodestruction following irradiation with an argon ion laser at 514.5 nm was determined by the 'MTT assay'. There appeared to be a 'threshold' effect of cellular PpIX content; cells that synthesised less than 140 ng mu g(-1) protein exhibited very little phototoxic damage, while cell lines having greater than 140 ng PpIX mu g(-1) protein exhibited a consistent phototoxic response. Among the cell lines which did undergo phototoxic damage, there was not a strict correlation between PpIX cellular content and ALA-induced phototoxicity. Desferal enhanced the PpIX content and phototoxic effect in the responsive cells. Fluorescence microscopy of the ALA-treated cells revealed marked accumulation of PpIX in mitochondria (rhodamine 123 co-staining). That the primary site of phototoxic damage is also the mitochondria was confirmed by electron micrographs of cells photosensitised with ALA-induced PpIX, which showed swelling of mitochondria within minutes after irradiation while other suborganelles appeared to be unaffected. The repair or further destruction of the mitochondria was fluence and cell-type dependent. The data from this study suggest that the basis of increased ALA-induced PpIX accumulation in tumours is a combination of various aspects of the metabolic process and pharmacokinetics and that the efficacy of photodestruction of malignancy will be determined not only by the rate of PpIX synthesis but also by specific cellular and tissue characteristics. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,WELLMAN LABS PHOTOMED,DEPT DERMATOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT UROL,BOSTON,MA 02114. UNIV VIENNA,SCH MED,DEPT DERMATOL & VENEROL,DIV SPECIAL & ENVIRONM DERMATOL,VIENNA,AUSTRIA. FU NIAMS NIH HHS [R29-AR38918-01] NR 37 TC 135 Z9 137 U1 0 U2 7 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1994 VL 70 IS 1 BP 21 EP 28 DI 10.1038/bjc.1994.244 PG 8 WC Oncology SC Oncology GA NW118 UT WOS:A1994NW11800005 PM 8018536 ER PT J AU KIM, I UCHIYAMA, H CHAUHAN, D ANDERSON, KC AF KIM, I UCHIYAMA, H CHAUHAN, D ANDERSON, KC TI CELL-SURFACE EXPRESSION AND FUNCTIONAL-SIGNIFICANCE OF ADHESION MOLECULES ON HUMAN MYELOMA-DERIVED CELL-LINES SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CELLULAR ADHESION MOLECULES; HUMAN MYELOMA-DERIVED CELL LINE; BONE MARROW STROMAL CELLS; INTERLEUKIN-6; MULTIPLE MYELOMA ID NON-HODGKINS-LYMPHOMA; MARROW STROMAL CELLS; PLASMA-CELLS; BONE-MARROW; MULTIPLE-MYELOMA; HOMING RECEPTOR; LEUKEMIA CELLS; GROWTH; INTERLEUKIN-6; ANTIGEN AB Multiple myeloma is characterized by the presence of malignant plasma cells predominantly localized in bone marrow. Our prior studies have suggested that human myeloma derived-cell lines adhere specifically to fibronectin and to bone marrow stromal cells (BMSCs) via beta 1 and beta 2 integrins as well as RGD peptide, and that tumour cell to BMSC contact triggers interleukin-6 (IL-6) secretion from BMSCs. Since IL-6 is a growth factor for myeloma, adhesion may be important in paracrine IL-6 mediated tumour cell growth. We therefore examined phenotypic expression of adhesion molecules on the U266 and IM-9 human myeloma-derived cell lines using the panel of monoclonal antibodies (MoAbs) directed at adhesion molecules submitted to the Vth International Conference on Human Leukocyte Differentiation Antigens. U266 and IM-9 myeloma cell lines express mainly CD29, CD49d, VLA-1, CD18, CD54, ICAM-2 and ICAM-3. In contrast, CD49b, VLA-3, CD49f, CD11b, VCAM-1, selectins and selectin-ligands were not expressed on these cell lines. Specific adherence of IM-9 cells to BMSC line LP101 was demonstrated which could be partially blocked by pre-incubation and culture of tumour cells with anti-pi integrin, anti-beta 2 integrin, anti-CD49d, anti-VLA-5, anti-CD11a, anti-CD44 and anti-CD54 MoAbs. The combination of these MoAbs (anti-CD29, CD18, CD11a, CD49d, VLA-5, CD44, CD54, ICAM-2, ICAM-3 MoAbs) decreased but did not completely abrogate binding of IM-9 to BMSCs. Moreover, increases in IL-6 secretion from BMSCs after adherence of IM-9 cells were also partially blocked by these MoAbs. These findings suggest that multiple adhesion pathways may mediate adherence of myeloma cell lines to BMSCs, localizing tumour cells in the marrow microenvironment and triggering IL-6 secretion by BMSCs which may augment tumour cell growth. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA50947] NR 31 TC 63 Z9 64 U1 0 U2 1 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 JUL PY 1994 VL 87 IS 3 BP 483 EP 493 DI 10.1111/j.1365-2141.1994.tb08302.x PG 11 WC Hematology SC Hematology GA NW748 UT WOS:A1994NW74800007 PM 7993788 ER PT J AU LEE, WS MOUSSAOUI, SM MOSKOWITZ, MA AF LEE, WS MOUSSAOUI, SM MOSKOWITZ, MA TI BLOCKADE BY ORAL OR PARENTERAL RPR-100893 (A NONPEPTIDE NK1 RECEPTOR ANTAGONIST) OF NEUROGENIC PLASMA-PROTEIN EXTRAVASATION WITHIN GUINEA-PIG DURA-MATER AND CONJUNCTIVA SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE MIGRAINE; NEUROGENIC INFLAMMATION; TACHYKININS; TRIGEMINAL GANGLION; NK-1 RECEPTOR ANTAGONIST ID VASCULAR HEAD PAIN; SUBSTANCE-P; BLOOD-VESSELS; RAT; MECHANISMS; INFLAMMATION; AGONISTS; RP-67580; BRAIN; IMMUNOREACTIVITY AB 1 The ability of an NK1 receptor antagonist, RPR 100893, and its enantiomer, RPR 103253 to block neurogenic plasma protein extravasation in guinea-pig dura mater and conjunctiva was assessed following I-125-labelled bovine serum albumin ([I-125]-BSA, 50 mu Ci kg(-1), i.v.) and unilateral electrical stimulation of the trigeminal ganglion (0.6 mA, 5 ms, 5 Hz, 5 min) or capsaicin administration (150 mu g kg(-1), i.v.). 2 When administered p.o. 60 min prior to electrical stimulation, RPR 100893 (greater than or equal to 0.1 mu g kg(-1)) decreased plasma protein extravasation in dura mater in a dose-dependent manner, whereas the enantiomer (10 or 100 mu g kg(-1), p.o.) was inactive. 3 When given i.v. 30 min prior to electrical stimulation, RPR 100893 (greater than or equal to 0.5 ng kg(-1)) significantly inhibited plasma protein extravasation in the dura mater evoked by electrical stimulation in a dose-dependent manner. 4 RPR 100893 (100 mu g kg(-1), p.o.) also reduced the leakage when given 45 min before the guinea-pigs were killed and 10, 40 and 80 min after electrical trigeminal stimulation. 5 RPR 100893 given p.o. dose-dependently inhibited capsaicin-induced plasma protein extravasation with ID(50)s of 7.4 mu g kg(-1) and 82 mu g kg(-1) for dura mater and conjunctiva, respectively. 6 These results are consistent with the contention that NK1 receptors mediate neurogenic plasma protein leakage following trigeminal stimulation, and suggest that NK1 receptor antagonists of the perhydroisoindolone series may be useful for treating migraine and cluster headaches. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROSURG SERV,STROKE RES LAB,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,NEUROL SERV,BOSTON,MA 02114. RHONE POULENC RORER,CTR RECH VITRY ALFORTVILLE,F-94403 VITRY SUR SEIN,FRANCE. RI Moskowitz, Michael/D-9916-2011 NR 40 TC 53 Z9 54 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 JUL PY 1994 VL 112 IS 3 BP 920 EP 924 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NV137 UT WOS:A1994NV13700034 PM 7921621 ER PT J AU MULLER, RT FITZGERALD, HE SULLIVAN, LA ZUCKER, RA AF MULLER, RT FITZGERALD, HE SULLIVAN, LA ZUCKER, RA TI SOCIAL SUPPORT AND STRESS FACTORS IN CHILD MALTREATMENT AMONG ALCOHOLIC FAMILIES SO CANADIAN JOURNAL OF BEHAVIOURAL SCIENCE-REVUE CANADIENNE DES SCIENCES DU COMPORTEMENT LA English DT Article; Proceedings Paper CT 53rd Annual Convention of the Canadian-Psychological-Association CY JUN 11, 1992 CL QUEBEC CITY, CANADA SP CANADIAN PSYCHOL ASSOC ID ADOLESCENT PSYCHOPATHOLOGY; SCREENING TEST; LIFE EVENTS; ABUSE; BEHAVIOR; FATHERS; SONS; PERSONALITY; VIOLENCE; MOTHERS AB The relationships among social support, stress, child maltreatment and child aggressiveness in alcoholic families were investigated. Subjects were 62 fathers, 65 mothers, and 65 target children. Participants consisted of families in which the biological parents were either married or cohabiting, and in which there was a male child between the ages of 3 and 5 years. Individual difference factors assessed were extent of social support, stress, child maltreatment, and child aggressiveness. Based on prior research, 3 process models were proposed and tested against one another using path analysis. For this high risk alcoholic sample, results suggested that for fathers, social support and stress were each independent direct predictors of child maltreatment. In contrast, for mothers, social support was an indirect predictor of child maltreatment, and it buffered (moderated) the effect of stress on child maltreatment. For both fathers and mothers, lifetime alcohol problems predicted extent of child maltreatment. The data also indicated that child maltreatment influenced child aggressiveness. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 86 TC 19 Z9 19 U1 3 U2 7 PU CANADIAN PSYCHOL ASSOC PI OTTAWA PA 151 SLATER ST, STE 205, OTTAWA ON K1P 5H3, CANADA SN 0008-400X J9 CAN J BEHAV SCI JI Can. J. Behav. Sci.-Rev. Can. Sci. Comport. PD JUL PY 1994 VL 26 IS 3 BP 438 EP 461 DI 10.1037/0008-400X.26.3.438 PG 24 WC Psychology, Multidisciplinary SC Psychology GA NW278 UT WOS:A1994NW27800007 ER PT J AU HUNCHAREK, M AF HUNCHAREK, M TI LONG-TERM SURVIVAL ASSOCIATED WITH METASTATIC SMALL-CELL CARCINOMA OF THE ESOPHAGUS TREATED BY CHEMOTHERAPY, AUTOLOGOUS BONE-MARROW TRANSPLANTATION, AND ADJUVANT RADIATION-THERAPY SO CANCER LA English DT Letter RP HUNCHAREK, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT,BOSTON,MA, USA. NR 1 TC 2 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 1994 VL 74 IS 1 BP 217 EP 217 DI 10.1002/1097-0142(19940701)74:1<217::AID-CNCR2820740133>3.0.CO;2-8 PG 1 WC Oncology SC Oncology GA NT715 UT WOS:A1994NT71500032 PM 8004578 ER PT J AU KOPANS, DB AF KOPANS, DB TI SCREENING FOR BREAST-CANCER AND MORTALITY REDUCTION AMONG WOMEN 40-49 YEARS OF AGE SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society National Conference on Breast Cancer CY AUG 26-28, 1993 CL BOSTON, MA SP AMER CANC SOC, AMER ACAD FAMILY PHYSICIANS, AMER COLL OBSTETRICIANS & GYNECOLOGISTS, AMER COLL RADIOL, AMER COLL SURGEONS COMMISS CANC, AMER OSTEOPATH ASSOC, AMER SOC PREVENT ONCOL, NATL ASSOC ONCOL SOCIAL WORKERS, NATL ASSOC SOCIAL WORKERS, ONCOL NURSING SOC, SOC SURG ONCOL DE BREAST CANCER; SCREENING; RANDOMIZED, CONTROLLED TRIALS ID MAMMOGRAPHY; TRIAL; SURVIVAL; RATES; SIZE AB The recent withdrawal of screening support for women ages 40-49 years is not scientifically supported. The subgroup analyses that have been used severely compromise the statistical power of the trials. None of the trials has the statistical power to be able to provide clear proof of benefit for screening women ages 40-49 years because none of the trials involved sufficient numbers of women in these age groups. Despite having not been designed to evaluate women ages 40-49 years as a separate group, five of the eight randomized, controlled trials have demonstrated mortality reductions for these women that range from 22% to 49%. In addition, data from other nonrandomized trials show that there is no difference in survival for women ages 40-49 years than for women ages 50-59 years. The detection rate for small, early cancers, using modern mammography, is similar for women in both decades. There is no scientific reason to believe that there is a sudden change in detection or cure at age 50 years, or even at menopause. The available data suggest that women ages 40-49 years can benefit from screening, just as can women ages 50-59 years. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,LEVEL 2,SUITE 219,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 31 TC 29 Z9 29 U1 1 U2 4 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 JUL 1 PY 1994 VL 74 IS 1 SU S BP 311 EP 322 PG 12 WC Oncology SC Oncology GA NU475 UT WOS:A1994NU47500014 PM 8004602 ER PT J AU AYASH, LJ AF AYASH, LJ TI HIGH-DOSE CHEMOTHERAPY WITH AUTOLOGOUS STEM-CELL SUPPORT FOR THE TREATMENT OF METASTATIC BREAST-CANCER SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society National Conference on Breast Cancer CY AUG 26-28, 1993 CL BOSTON, MA SP AMER CANC SOC, AMER ACAD FAMILY PHYSICIANS, AMER COLL OBSTETRICIANS & GYNECOLOGISTS, AMER COLL RADIOL, AMER COLL SURGEONS COMMISS CANC, AMER OSTEOPATH ASSOC, AMER SOC PREVENT ONCOL, NATL ASSOC ONCOL SOCIAL WORKERS, NATL ASSOC SOCIAL WORKERS, ONCOL NURSING SOC, SOC SURG ONCOL DE BREAST CANCER; BONE MARROW TRANSPLANTATION; HIGH DOSE CHEMOTHERAPY ID BONE-MARROW SUPPORT; PHASE-I-II; CYCLOPHOSPHAMIDE; THIOTEPA; COMBINATION; THERAPY; TRANSPLANTATION; CARBOPLATIN; INVITRO AB The overall median survival of women with advanced or high risk primary disease has not changed with conventional chemotherapy. Regimens employing high dose chemotherapy with autologous stem cell support (ABMT) have been developed with the hope of optimizing tumor response and increasing survival. Early Phase I studies of patients with advanced refractory disease demonstrated the feasibility of administering agents in doses 5-30 times higher than those conventionally used. These studies achieved high response rates of short duration. Second generation studies combined an induction phase followed by one high dose intensification at the time of maximum tumor response. To date, between 15 and 30% of women with metastatic disease remain progression free after being treated with this approach, with median lengths of follow-up approaching 36 months in the larger series. With the advent of hematologic support, such as blood stem cells and colony stimulating factors, the morbidity, mortality, and costs associated with this treatment have been reduced substantially. These supports now allow for two or more cycles of high dose intensification to be employed, to exploit the potential of dose intensity to optimize response. Recent single-institution studies using ABMT for high risk Stages II and III breast cancer have reported preliminary findings suggesting a prolonged disease free survival. The cooperative groups now have begun prospective randomized studies in high risk women with Stages II and III disease with 10 or more positive axillary lymph nodes, and soon will study the efficacy of ABMT in women with inflammatory or locally unresectable breast cancer (Stage IIIB). RP AYASH, LJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 20 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 JUL 1 PY 1994 VL 74 IS 1 SU S BP 532 EP 535 PG 4 WC Oncology SC Oncology GA NU475 UT WOS:A1994NU47500041 PM 8004629 ER PT J AU YUAN, F LEUNIG, M HUANG, SK BERK, DA PAPAHADJOPOULOS, D JAIN, RK AF YUAN, F LEUNIG, M HUANG, SK BERK, DA PAPAHADJOPOULOS, D JAIN, RK TI MICROVASCULAR PERMEABILITY AND INTERSTITIAL PENETRATION OF STERICALLY STABILIZED (STEALTH) LIPOSOMES IN A HUMAN TUMOR XENOGRAFT SO CANCER RESEARCH LA English DT Note ID HUMAN ADENOCARCINOMA LS174T; BASEMENT-MEMBRANES; COLON-CARCINOMA; BLOOD-VESSELS; MICE BEARING; SCID MICE; TRANSPORT; TISSUE; PHARMACOKINETICS; LOCALIZATION AB Microvascular permeability and interstitial penetration of sterically stabilized liposomes in both normal s.c. tissue and human colon adenocarcinoma LS174T xenograft were quantified by using the dorsal skinfold chamber implanted in severe combined immunodeficient mice and intravital fluorescence microscopy. Significant extravascular accumulation was the dominant feature of liposome distribution in tumors, whereas only minimal intramural accumulation in postcapillary and collecting venules was observed in normal s.c. tissue. The extravasated liposomes in tumors distributed heterogeneously and formed perivascular clusters that did not move significantly and could be observed for up to 1 week. The effective permeability of tumor vessels to liposomes (2.0 +/- 1.6 x 10(-8) cm/s; n = 23) was six times smaller than that to bovine serum albumin (1.2 +/- 0.5 x 10(-7) cm/s; n = 6). These results provide new insights into the mechanisms of transendothelial pathways of liposomes and improvements in liposome-mediated drug delivery. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,CANC RES INST,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PHARMACOL,SAN FRANCISCO,CA 94143. RP YUAN, F (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. RI Yuan, Fan/A-1287-2011; Berk, David/A-4863-2012; Leunig, Michael/E-7951-2017 OI Berk, David/0000-0002-3855-6886; Leunig, Michael/0000-0002-2036-5416 FU NCI NIH HHS [CA59255, R35-CA-56591] NR 24 TC 642 Z9 652 U1 5 U2 52 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 JUL 1 PY 1994 VL 54 IS 13 BP 3352 EP 3356 PG 5 WC Oncology SC Oncology GA NU488 UT WOS:A1994NU48800007 PM 8012948 ER PT J AU FALK, E FALLON, JT MAILHAC, A FERNANDEZORTIZ, A MEYER, BJ WENG, D SHAH, PK BADIMON, JJ FUSTER, V AF FALK, E FALLON, JT MAILHAC, A FERNANDEZORTIZ, A MEYER, BJ WENG, D SHAH, PK BADIMON, JJ FUSTER, V TI MURAMIDASE - A USEFUL MONOCYTE/MACROPHAGE IMMUNOCYTOCHEMICAL MARKER IN SWINE, OF SPECIAL INTEREST IN EXPERIMENTAL CARDIOVASCULAR-DISEASE SO CARDIOVASCULAR PATHOLOGY LA English DT Article ID MONONUCLEAR PHAGOCYTES; PARAFFIN SECTIONS; LYSOZYME; IMMUNOPEROXIDASE; TISSUES; CELLS; ALPHA-1-ANTICHYMOTRYPSIN; ALPHA-1-ANTITRYPSIN; SECRETION; SMEARS AB The reliability of a rabbit polyclonal antibody against muramidase to identify monocytes/macrophages in swine was evaluated by immunostaining of cell smears and formaldehyde-fixed, paraffin-embedded tissue sections. Blood in tissue sections, cell smears (peripheral blood, buffy coat, and isolated mononuclear cells), and cultured mononuclear cells (adherent monocytes) contained positively stained cells with a morphology and in a number corresponding to that expected for a monocyte marker. Polymorphonuclear leukocytes (PMN), lymphocytes, and platelets were negative. In normal organs and tissues, mesenchymal cells with a distribution similar to that expected for macrophages were found to stain positively for muramidase. In pathologic tissues, positively stained inflammatory cells were identified in wounds, infected lungs, recently infarcted myocardium, and acute (variable numbers), organizing (often many), and healed (usually few) arterial thrombi. Enzymatic unmasking of antigenic determinants by trypsinization was necessary to achieve strong and consistent staining of monocytes/macrophages in tissue sections. A variety of epithelial cells of no differential diagnostic significance for monocyte/macrophage identification (e.g., renal proximal tubular cells) also stained positive for muramidase. The staining pattern of muramidase in swine corresponds to that described in humans, in whom muramidase has been shown to be a valuable marker of monocytes/macrophages. Swine PMN were, however, not stained or only weakly stained, whereas human PMN reportedly are strongly positive. As in humans, swine cardiac myocytes, smooth muscle cells, endothelial cells, lymphocytes, and platelets were consistently negative. This antibody against muramidase is a useful immunohistochemical marker for swine monocytes/macrophages in formaldehyde-fixed, paraffin-embedded tissues. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIOVASC PATHOL RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. CEDARS SINAI MED CTR,DIV CARDIOL,LOS ANGELES,CA 90048. RI Fuster, Valentin/H-4319-2015; Fernandez-Ortiz, Antonio/B-2227-2017 OI Fuster, Valentin/0000-0002-9043-9986; Fernandez-Ortiz, Antonio/0000-0002-3239-1910 NR 20 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JUL-SEP PY 1994 VL 3 IS 3 BP 183 EP 189 DI 10.1016/1054-8807(94)90028-0 PG 7 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA PC335 UT WOS:A1994PC33500007 PM 25990995 ER PT J AU KASHKET, S YASKELL, T MURPHY, JE AF KASHKET, S YASKELL, T MURPHY, JE TI DELAYED-EFFECT OF WHEAT-STARCH IN FOODS ON THE INTRAORAL DEMINERALIZATION OF ENAMEL SO CARIES RESEARCH LA English DT Article DE ENAMEL DEMINERALIZATION, INTRAORAL; FOOD ENTRAPMENT; IODIDE PENETRABILITY; MALTASE; PLAQUE PH; STARCH; STREPTOCOCCUS MUTANS; SUCROSE ID SUCROSE; CARIES; RATS; CARIOGENICITY; PLAQUE; PH AB There is considerable evidence for an association between dental caries and food starches. However, the intraoral utilization of starch may be quite complex, giving rise to conflicting results. Demineralization induced by unsweetened cookies was examined in an intraoral model system that utilized palatal appliances containing blocks of bovine enamel. The enamel surfaces were covered with either a filter paper disc to trap sugars or a layer of Streptococcus mutans to metabolize the sugars and bring about enamel demineralization. Demineralization was determined as an increase in porosity with respect to iodide ions (delta Ip). Measurements revealed a rapid elevation and maintenance of high levels of maltose in the plaque space after ingestion of the unsweetened or sweet cookies. Entrapped food particles appeared to serve as a reservoir of maltose. Unsweetened cookies brought about enamel demineralization, but the pH of the streptococcal plaque fell slowly and the initiation of demineralization was delayed. Thus, delta Ip and plaque pH were -0.3+/-1.3 U and 6.1+/-0.3, respectively, after 15 min. The delay was shown to be related to the need to induce the acidogenic streptococci to metabolize maltose. Once induced, delta Ip rose rapidly and reached a maximum at 45 min. Sweet cookies released sucrose and maltose and brought about a rapid onset of demineralization. In summary, the data demonstrated (1) that maltose was released rapidly from unsweetened cookie particles and diffused into the plaque space of the model system and (2) that maltose-dependent demineralization of enamel required time for the induction of the streptococcal cells. The present observations may help in understanding earlier conflicting reports on the cariogenic potentials of starch-containing foods. C1 FORSYTH DENT CTR,CTR RES ORAL BIOL EFFECTS FOODS,BOSTON,MA. RP KASHKET, S (reprint author), FORSYTH DENT CTR,DEPT NUTR,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-05253] NR 34 TC 14 Z9 14 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PD JUL-AUG PY 1994 VL 28 IS 4 BP 291 EP 296 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NU083 UT WOS:A1994NU08300012 PM 8069887 ER PT J AU PERKINS, DL LISTMAN, JA WANG, YS HO, SS FINN, PW RIMM, IJ AF PERKINS, DL LISTMAN, JA WANG, YS HO, SS FINN, PW RIMM, IJ TI DIFFERENTIAL EXPRESSION OF ACTIVATION MARKERS DURING TOLERANCE INDUCTION BY SUPERANTIGENS IN T-CELL RECEPTOR (BETA-CHAIN) TRANSGENIC MICE SO CELLULAR IMMUNOLOGY LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; MONOCLONAL-ANTIBODY; EXTRATHYMIC TOLERANCE; ANTIGEN RECEPTOR; LYMPHOCYTES-T; ANERGY; CLONES; PEPTIDES; PROLIFERATION; TOXICITY AB To investigate the process of tolerance induction we have developed an in vivo model using TCR beta-chain transgenic mice tolerized with the superantigen staphylococcal enterotoxin B. We have previously demonstrated that tolerized peripheral T cells were anergic when stimulated in vitro with immunogenic peptides, superantigens, mitogens, and immobilized anti-TCR mAb. However, the development of anergy is preceded by an induction phase which produces expansion followed by contraction of the peripheral T cell population presumably due to proliferation and programmed cell death, respectively. The current experiments focus on the induction phase of tolerance. A kinetic functional analysis showed that the inhibition of proliferation was apparent 2-3 days post-tolerization. Interestingly, the inhibition of proliferation correlated with the loss of IL-2R alpha expression, which occurred 2 days post-tolerization following an initial increase in IL-2R alpha expression. In addition, the expression of multiple activation markers including CD44, Ly-6A/E, and very early activation marker H1.2F3 is induced, whereas the expression of CD45RB is decreased during tolerance induction. Elevated expression of Ly-6A/E persists up to 28 days post-tolerization; however, altered expression of the other markers does not persist and near baseline levels of the other markers are noted 7 to 28 days post-tolerization. These results show that tolerance induction is an active process which has functional and phenotypic similarities to antigen-specific immunity. However, tolerance induction in our system differs from immunity in terms of the early loss of IL-2R alpha expression, the persistent increased expression of Ly-6A/E, and the lack of development of CD45RB(lo) memory-type T cells. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. CHILDRENS HOSP,DIV RENAL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV COMBINED PULM,BOSTON,MA 02115. BETH ISRAEL HOSP,BOSTON,MA 02215. DANA FARBER CANC INST,DIV PEDIAT HEMATOL ONCOL,BOSTON,MA. RP PERKINS, DL (reprint author), BRIGHAM & WOMENS HOSP,IMMUNOGENET & TRANSPLANTAT LAB,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [AI-31517] NR 38 TC 6 Z9 7 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 JUL PY 1994 VL 156 IS 2 BP 310 EP 321 DI 10.1006/cimm.1994.1177 PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NX220 UT WOS:A1994NX22000005 PM 8025950 ER PT J AU HAREGEWOIN, A SOLOMON, K HOM, RC SOMAN, G BERGELSON, JM BHAN, AK FINBERG, RW AF HAREGEWOIN, A SOLOMON, K HOM, RC SOMAN, G BERGELSON, JM BHAN, AK FINBERG, RW TI CELLULAR EXPRESSION OF A GPI-LINKED T-CELL ACTIVATION PROTEIN SO CELLULAR IMMUNOLOGY LA English DT Article ID DECAY-ACCELERATING FACTOR; GLYCOSYL-PHOSPHATIDYLINOSITOL; LYMPHOCYTES; MOLECULES; PLATELETS; RECEPTOR AB A T cell activation protein was identified by generating a monoclonal antibody (anti-D2) against a gamma delta T cell receptor bearing gibbon ape T cell line (MLA144). Immunoprecipitation studies revealed three polypeptides of 180, 150, and 120 kDa. The antigen was also found to be expressed on endothelial cells in vivo and in vitro and on tumor cell lines from a variety of tissues. Studies performed using a variety of antibodies reveal this protein to be identical to an endothelial cell protein previously identified by several antibodies to T cell activation proteins (CDwl09). We demonstrate that this protein is anchored in the membrane via a glycosylphosphatidylinositol (GPI) tail in T cells, tumor cells, and endothelial cells. An analysis of tissue sections reveals this protein to be normally highly expressed on vascular endothelial cells. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 NR 22 TC 32 Z9 33 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL PY 1994 VL 156 IS 2 BP 357 EP 370 DI 10.1006/cimm.1994.1181 PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NX220 UT WOS:A1994NX22000009 PM 8025953 ER PT J AU FILIPEK, PA RICHELME, C KENNEDY, DN CAVINESS, VS AF FILIPEK, PA RICHELME, C KENNEDY, DN CAVINESS, VS TI YOUNG-ADULT HUMAN BRAIN - AN MRI-BASED MORPHOMETRIC ANALYSIS SO CEREBRAL CORTEX LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; LEFT-RIGHT ASYMMETRIES; HUMAN CEREBRAL-CORTEX; IMAGING-BASED VOLUME; HUMAN VISUAL-CORTEX; SEXUAL-DIFFERENTIATION; TEMPORAL-LOBE; CORPUS-CALLOSUM; FUNCTIONAL ASYMMETRY; SYNAPSE ELIMINATION AB Morphometric analysis was performed on three-dimensional MRI scans of 10 male and 10 female young adults with four principal objectives: (1) to characterize in vivo volumes of whole brain and substructures, (2) to explore volumetric symmetry in bilateral structures, (3) to consider the extent to which volumetric measures are dimorphic in the male and female brain, and (4) to provide a normal volumetric database for the young adult brain. Total brain volumes ranged between 1173 and 1626 cm(3). All bilateral structures were symmetric or nearly symmetric in volume, with the exception of a slightly larger right neocortex and amygdala, and larger left lateral ventricle. Male brains were larger in volume than female brains, a difference that reached significance for cerebellar but not for cerebral hemisphere volume. In females, there was less cerebral white matter while caudate volume was larger than in the male brains. The proportions of caudate and hippocampus relative to total cerebral volumes were larger in females than in males. These four measures accurately predicted gender in 85% of the subjects by discriminant analysis. No gender differences were noted in the structural symmetry analysis. These results represent the first step in establishing a comprehensive database of morphometric parameters, with unexpected findings relative to brain symmetry and sexual dimorphism. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR MORPHOMETR ANAL,RADIOL SERV,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR MORPHOMETR ANAL,PEDIAT NEUROL SERV,BOSTON,MA 02129. RI Kennedy, David/H-3627-2012 FU NICHD NIH HHS [HD 27802]; NINDS NIH HHS [NS 20489, NS 24279] NR 97 TC 413 Z9 418 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL-AUG PY 1994 VL 4 IS 4 BP 344 EP 360 DI 10.1093/cercor/4.4.344 PG 17 WC Neurosciences SC Neurosciences & Neurology GA NW981 UT WOS:A1994NW98100002 PM 7950308 ER PT J AU SCHWAMMENTHAL, E CHEN, CG BENNING, F BLOCK, M BREITHARDT, G LEVINE, RA AF SCHWAMMENTHAL, E CHEN, CG BENNING, F BLOCK, M BREITHARDT, G LEVINE, RA TI DYNAMICS OF MITRAL REGURGITANT FLOW AND ORIFICE AREA - PHYSIOLOGICAL APPLICATION OF THE PROXIMAL FLOW CONVERGENCE METHOD - CLINICAL-DATA AND EXPERIMENTAL TESTING SO CIRCULATION LA English DT Article DE MITRAL VALVE; DOPPLER FLOW ID INTERVENTRICULAR SEPTAL MOTION; DOPPLER ECHOCARDIOGRAPHY; VALVULAR REGURGITATION; NONINVASIVE ESTIMATION; VELOCITY PROFILE; CARDIAC-OUTPUT; VALVE ANNULUS; QUANTIFICATION; THERAPY; VOLUME AB Background The proximal how convergence method, a quantitative color Doppler flow technique, has been validated recently for calculating regurgitant flow and orifice area. We investigated the potential of the method as a tool to study different pathophysiological mechanisms of mitral valve incompetence by assessing the time course of regurgitant flow and orifice area and analyzed the implications for quantification of mitral regurgitation. Methods and Results Fifty-six consecutive patients with mitral regurgitation of different etiologies were studied. The instantaneous regurgitant flow rate Q((t)) was computed from color M-mode recordings of the proximal flow convergence region and divided by the corresponding orifice velocity V-(t) to obtain the instantaneous orifice area A((t)). Regurgitant stroke volume (RSV) was obtained by integrating Q((t)). Mean regurgitant flow rate Qm( )was calculated by RSV divided by regurgitation time. Peak-to-mean regurgitant flow rates Q(p)/Q(m) and orifice areas A(p)/A(m) were calculated to assess the phasic character of Q((t)) and P-(t) In the first 24 patients (group 1), computation of Q(m) and RSV from the color Doppler recordings was compared with the conventional pulsed Doppler method (r=.94, SEE=29.4 mL/s and r=.95, SEE=9.7 mL) as well as with angiography (r(s)=.93 and r(s)=.94, P<.001). The temporal variation of Q((t)) and A((t)) was studied in the next 32 patients (group 2): In functional regurgitation in dilated cardiomyopathy (n=12), there was a constant decrease in A((t)) throughout systole with an increase during left ventricular relaxation; A(p)/A(m) was 5.49+/-3.17. In mitral valve prolapse (n=6), A((t)) was small in early systole, increasing substantially in midsystole, and decreasing mildly during left ventricular relaxation; A(p)/A(m) was 2.48+/-0.26. In rheumatic mitral regurgitation (n=14), a roughly constant regurgitant orifice area during most of systole was found in 4 patients. In the other patients there was significant variation of A((t)) and the time of its maximum; A(p)/A(m) was 1.81+/-0.56. ANOVA demonstrated that the differences in A(p)/A(m) were related to the etiology of mitral regurgitation (P<.0001). To verify that the calculated variation in regurgitant orifice area during the cardiac cycle reflects an actual variation, the ability of the method to predict a constant orifice area throughout systole was tested experimentally in a canine model of mitral regurgitation. Five flow stages were produced by implanting fixed grommet orifices of different sizes into the anterior mitral leaflet. A constant regurgitant orifice area was correctly predicted throughout systole with a mean percent error of -1.8+/-4% (from -6.9% to +5.8%); the standard deviation of the individual curves calculated at 10% intervals during systole averaged 13.3% (from 3.6% to 19.6%). In addition, functional mitral regurgitation caused by ventricular dysfunction was produced pharmacologically in five dogs, and the color M-mode recordings of the proximal flow convergence region were obtained with the transducer placed directly on the heart instead of the chest, thus ruling out a significant effect of translational motion on the observed flow pattern. The pattern of regurgitant how variation was identical to that observed in patients. Conclusions The proximal flow convergence method demonstrates that regurgitant flow and orifice area vary throughout systole in distinct patterns characteristic of the underlying mechanism of mitral incompetence. Therefore, in addition to the potential of the method as a tool to quantify mitral regurgitation, it allows analysis of the pathophysiology of regurgitation in the individual patient, which may be helpful in clinical decision making. Calculating mitral regurgitant flow rate and volume from the time-varying proximal how field tie, without assuming a constant orifice area that would produce overestimation in individual patients) provides excellent agreement with independent techniques and agrees well with angiography. C1 UNIV MUNSTER HOSP,DEPT CARDIOL & ANGIOL,MUNSTER,GERMANY. RP SCHWAMMENTHAL, E (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC ULTRASOUND LAB,VINCENT BURNHAM 5,2F,BOSTON,MA 02114, USA. NR 66 TC 177 Z9 178 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 JUL PY 1994 VL 90 IS 1 BP 307 EP 322 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NW547 UT WOS:A1994NW54700043 PM 8026013 ER PT J AU FINGEROTH, JD ROTH, RS TALCOTT, JA RINALDI, MG AF FINGEROTH, JD ROTH, RS TALCOTT, JA RINALDI, MG TI ZYGOMYCOSIS DUE TO MUCOR-CIRCINELLOIDES IN A NEUTROPENIC PATIENT RECEIVING CHEMOTHERAPY FOR ACUTE MYELOGENOUS LEUKEMIA SO CLINICAL INFECTIOUS DISEASES LA English DT Note ID DISSEMINATED MUCORMYCOSIS AB Mucor circinelloides form circinelloides has rarely been associated with human disease, even in immunocompromised patients. We report a case of cutaneous zygomycosis caused by M. circinelloides in a 23-year-old neutropenic woman receiving consolidation chemotherapy for acute myelogenous leukemia. The organism was exquisitely susceptible to amphotericin B. Despite the fact that the patient was profoundly neutropenic for an additional 3 weeks, the lesions began to resolve during therapy, and no surgical debridement was required. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. RP FINGEROTH, JD (reprint author), HARVARD UNIV,DANA FARBER CANC INST,INFECT DIS LAB,44 BINNEY ST,BOSTON,MA 02115, USA. NR 15 TC 26 Z9 27 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 JUL PY 1994 VL 19 IS 1 BP 135 EP 137 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NX665 UT WOS:A1994NX66500020 PM 7948514 ER PT J AU BOLAND, GW LEE, MJ CATS, A MUELLER, PR AF BOLAND, GW LEE, MJ CATS, A MUELLER, PR TI PSEUDOMEMBRANOUS COLITIS - DIAGNOSTIC SENSITIVITY OF THE ABDOMINAL PLAIN RADIOGRAPH SO CLINICAL RADIOLOGY LA English DT Article ID CT EVALUATION AB We performed a retrospective study to determine the incidence of plain radiographic abnormalities in patients with pseudomembranous colitis (PMC). One hundred and fifty-two plain radiographs of the abdomen (taken within 3 days of pseudomembranous colitis diagnosis) from 152 patients with pseudomembranous colitis were reviewed. Forty-eight of 152 (32%) plain radiographs were abnormal, demonstrating: colonic ileus in 48/152 (32%), small bowel ileus in 31/152 (20%), ascites in 10/152 (7%), and nodular haustral thickening in 28/152 (18%). The distribution in 48 patients with colonic ileus included: right colon, 41/48 (86%), transverse colon, 35/48 (72%), and left colon, 26/48 (55%). Distribution in 28 patients with nodular haustral thickening included: right colon, 5/28 (18%), transverse colon, 15/28 (54%), and left colon, 14/28 (50%). Radiographic changes were non-specific in 32% of patients with changes more specific to PMC in only 18%. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 10 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD JUL PY 1994 VL 49 IS 7 BP 473 EP 475 DI 10.1016/S0009-9260(05)81744-1 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX890 UT WOS:A1994NX89000008 PM 8088041 ER PT J AU VACANTI, CA UPTON, J AF VACANTI, CA UPTON, J TI TISSUE-ENGINEERED MORPHOGENESIS OF CARTILAGE AND BONE BY MEANS OF CELL TRANSPLANTATION USING SYNTHETIC BIODEGRADABLE POLYMER MATRICES SO CLINICS IN PLASTIC SURGERY LA English DT Article RP VACANTI, CA (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA WHITE 5,TISSUE ENGN LAB,BOSTON,MA 02114, USA. NR 0 TC 110 Z9 173 U1 2 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0094-1298 J9 CLIN PLAST SURG JI Clin. Plast. Surg. PD JUL PY 1994 VL 21 IS 3 BP 445 EP 462 PG 18 WC Surgery SC Surgery GA NW957 UT WOS:A1994NW95700013 PM 7924143 ER PT J AU SMITH, JD NELSON, DGK GROHSHKOPF, LA APPLETON, T AF SMITH, JD NELSON, DGK GROHSHKOPF, LA APPLETON, T TI WHAT CHILD IS THIS - WHAT INTERVAL WAS THAT - FAMILIAR TUNES AND MUSIC PERCEPTION IN NOVICE LISTENERS SO COGNITION LA English DT Article ID CATEGORICAL PERCEPTION; TONAL FUNCTIONS; HIERARCHY; MELODIES; CONTEXT AB In the laboratory, musical novices often seem insensitive even to basic structural elements of music (octaves, intervals, etc.), undermining long-held theories of music perception, and threatening to leave current theories applicable only to experts. Consequently it is important to demonstrate novices' basic listening competence where possible. Two experiments examined the perception of musical intervals (minor thirds, major thirds and perfect fourths) by musical novices. Subjects received either standard instructions or familiar folk-tune labels to aid performance. The folk-tune labels greatly improved identification performance, producing expert-caliber performance by some musically inexperienced subjects. The effectiveness of the folk-tune manipulation was much more limited in a difficult discrimination task. The results suggest that novices do have some basic competence when assayed appropriately, and that familiar musical tokens may be a critical element in such assays. Larger implications of the role of familiarity in novices' competence are discussed, including those that relate to music cognition and aesthetics. C1 SWARTHMORE COLL,DEPT PSYCHOL,SWARTHMORE,PA 19081. MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,BOSTON,MA 02114. RP SMITH, JD (reprint author), SUNY BUFFALO,DEPT PSYCHOL,PK HALL,BUFFALO,NY 14260, USA. NR 60 TC 41 Z9 42 U1 5 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0010-0277 J9 COGNITION JI Cognition PD JUL PY 1994 VL 52 IS 1 BP 23 EP 54 PG 32 WC Psychology, Experimental SC Psychology GA NW234 UT WOS:A1994NW23400002 PM 7924198 ER PT J AU LIPINSKI, JF POPE, HG AF LIPINSKI, JF POPE, HG TI DO FLASHBACKS REPRESENT OBSESSIONAL IMAGERY SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID DISORDER C1 MASSACHUSETTS GEN HOSP,OBSESS COMPULS DISORDER CLIN,PSYCHIAT SERV,BOSTON,MA 02114. MCLEAN HOSP,BIOL PSYCHIAT LAB,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. NR 9 TC 32 Z9 32 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JUL-AUG PY 1994 VL 35 IS 4 BP 245 EP 247 DI 10.1016/0010-440X(94)90014-0 PG 3 WC Psychiatry SC Psychiatry GA NX037 UT WOS:A1994NX03700001 PM 7956178 ER PT J AU MEAD, MD HYMAN, L GRIMSON, R SCHEIN, OD AF MEAD, MD HYMAN, L GRIMSON, R SCHEIN, OD TI PRIMARY GRAFT FAILURE - A CASE-CONTROL INVESTIGATION OF A PURPORTED CLUSTER SO CORNEA LA English DT Article DE PENETRATING KERATOPLASTY; PRIMARY GRAFT FAILURE; RISK FACTORS AB Primary graft failure is a rare but major complication of penetrating keratoplasty. An apparent clustering of four cases during a 1-month period led to a review of all 778 keratoplasties performed by nine surgeons at Massachusetts Eye and Ear Infirmary from July 1, 1986 to June 30, 1988. The objectives of this study were (a) to investigate the possibility that cases of primary graft failure occurred in clusters within their physical environment of space, time, and personnel and (b) to determine the frequency of and evaluate possible risk factors for primary graft failure. Twenty-one cases of primary graft failure were found, resulting in an incidence rate of 2.7% during this period. A 13.3% incidence of primary graft failure was found in donor mates, suggesting improper tissue preparation. The charts and eye bank records of the 21 cases and 84 age-matched controls, randomly selected from the group of all keratoplasties, were reviewed for donor-, recipient-, surgeon-, and surgery-related characteristics. Improper tissue preparation was not associated with primary graft failure. An individual surgeon was the most significant risk factor [odds ratio = 6 (95% CI: 2.1-17.0)]. RP MEAD, MD (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OPHTHALM CONSULTANTS BOSTON,CTR EYE RES,BOSTON,MA 02114, USA. NR 0 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 1994 VL 13 IS 4 BP 310 EP 316 DI 10.1097/00003226-199407000-00005 PG 7 WC Ophthalmology SC Ophthalmology GA NT977 UT WOS:A1994NT97700005 PM 7924330 ER PT J AU DELAMAZA, MS FOSTER, CS AF DELAMAZA, MS FOSTER, CS TI PERIPHERAL ULCERATIVE KERATITIS AND MALIGNANCIES SO CORNEA LA English DT Article DE PERIPHERAL ULCERATIVE KERATITIS; MALIGNANCY; LEUKEMIA; SEBACEOUS CELL CARCINOMA AB Although systemic and local autoimmune diseases are the primary possibilities in the differential diagnosis of non-infectious peripheral ulcerative keratitis (PUK), other unusual etiologies such as systemic or local malignancies also must be considered. We report on two patients with PUK whose study led to the discovery and subsequent treatment of a chronic myelogenous leukemia and a sebaceous cell carcinoma of the eyelid, respectively. The results emphasize the need for meticulous diagnostic pursuit, including the possibility of malignancy in patients with peripheral ulcerative keratitis. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,OCULAR IMMUNOL SERV,243 CHARLES ST,BOSTON,MA 02114. NR 0 TC 6 Z9 8 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 1994 VL 13 IS 4 BP 364 EP 367 DI 10.1097/00003226-199407000-00014 PG 4 WC Ophthalmology SC Ophthalmology GA NT977 UT WOS:A1994NT97700014 ER PT J AU WALLER, SG PROANO, R GUDERIAN, R AF WALLER, SG PROANO, R GUDERIAN, R TI WEST-INDIAN PUNCTATE KERATOPATHY IN ECUADOR SO CORNEA LA English DT Letter RP WALLER, SG (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,CORNEA SERV,BOSTON,MA 02114, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3740 J9 CORNEA JI Cornea PD JUL PY 1994 VL 13 IS 4 BP 377 EP 378 DI 10.1097/00003226-199407000-00019 PG 2 WC Ophthalmology SC Ophthalmology GA NT977 UT WOS:A1994NT97700019 PM 7924343 ER PT J AU DAGATA, IDA WINTER, HS AF DAGATA, IDA WINTER, HS TI PEDIATRIC INFLAMMATORY BOWEL-DISEASE SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article AB This manuscript highlights recent advances relevant to pediatric patients with inflammatory bowel disease. Four areas are presented: growth failure, diagnosis and pathobiology, therapy, and clinical associations. Articles most likely to affect investigators and clinicians working on issues of importance to children and adolescents with Crohn's disease and ulcerative colitis were selected. Growth failure is a common and frequently serious problem in the pediatric population affected by inflammatory bowel disease. In 1993, both prospective and retrospective studies evaluated the effects of various treatment regimens. The role of pharmacotherapy and hormones in modifying alterations of growth were determined. Cytokines were studied as possible diagnostic tools in the clinical evaluation of disease and their role in the pathogenesis of mucosal inflammation became somewhat better defined, but much more complicated. The relationship between immunology, genetics, and clinical disease became clearer with the introduction of antineutrophil cytoplasmic antibodies in differentiating between Crohn's disease and ulcerative colitis. Therapy with immunosuppressive agents and reassessment Of the role of surgical management of inflammatory bowel disease in children were the major therapeutic advances, although new agents appropriate for children are on the horizon. An interesting series of case reports highlighted aspects of the disease that are unique to the pediatric population. 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 JUL PY 1994 VL 10 IS 4 BP 404 EP 408 DI 10.1097/00001574-199407000-00007 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NY266 UT WOS:A1994NY26600007 ER PT J AU SOUBA, WW AF SOUBA, WW TI CYTOKINE CONTROL OF NUTRITION AND METABOLISM IN CRITICAL ILLNESS SO CURRENT PROBLEMS IN SURGERY LA English DT Review ID TUMOR-NECROSIS-FACTOR; ACUTE-PHASE RESPONSE; ARTERY ENDOTHELIAL-CELLS; L-ARGININE TRANSPORT; DEPENDENT GLUTAMINE TRANSPORT; HEPATOCYTE-STIMULATING FACTOR; LIPOPROTEIN-LIPASE ACTIVITY; AMINO-ACID-TRANSPORT; RAT SKELETAL-MUSCLE; FACTOR-ALPHA C1 MASSACHUSETTS GEN HOSP,NUTR SUPPORT SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SOUBA, WW (reprint author), MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,BOSTON,MA 02114, USA. NR 157 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0011-3840 J9 CURR PROB SURG JI Curr. Probl. Surg. PD JUL PY 1994 VL 31 IS 7 BP 579 EP 643 PG 65 WC Surgery SC Surgery GA NX657 UT WOS:A1994NX65700001 ER PT J AU COX, DJ GONDERFREDERICK, L ANDERSON, R SCHLUNDT, D JACOBSON, A MARERRO, D CLARKE, W AF COX, DJ GONDERFREDERICK, L ANDERSON, R SCHLUNDT, D JACOBSON, A MARERRO, D CLARKE, W TI PROFESSIONALS BELIEFS ABOUT USEFUL SYMPTOMS OF HYPOGLYCEMIA SO DIABETES CARE LA English DT Letter ID INSULIN-INDUCED HYPOGLYCEMIA; IDDM C1 UNIV MICHIGAN,ANN ARBOR,MI 48109. VANDERBILT UNIV,NASHVILLE,TN. JOSLIN DIABET CTR,BOSTON,MA 02215. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. RP COX, DJ (reprint author), UNIV VIRGINIA,HLTH SCI CTR,CHARLOTTESVILLE,VA 22903, USA. FU NCRR NIH HHS [RR-00847]; NIDDK NIH HHS [R01-DK8288] NR 6 TC 2 Z9 2 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1994 VL 17 IS 7 BP 776 EP 777 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU592 UT WOS:A1994NU59200024 PM 7924793 ER PT J AU PRICOLO, VE SHELLITO, PC AF PRICOLO, VE SHELLITO, PC TI SURGERY FOR RADIATION-INJURY TO THE LARGE-INTESTINE - VARIABLES INFLUENCING OUTCOME SO DISEASES OF THE COLON & RECTUM LA English DT Article DE LARGE INTESTINE; SURGERY; RADIATION THERAPY; RADIATION ENTERITIS ID SURGICAL-TREATMENT; SLEEVE ANASTOMOSIS; UTERINE CERVIX; LASER THERAPY; MANAGEMENT; RECTUM; COMPLICATIONS; CARCINOMA; COLON AB PURPOSE: Surgery for colorectal radiation injury is technically difficult and often followed by complications. This study evaluates factors affecting outcome. METHODS: A retrospective 30-year review was carried out. Preoperative characteristics and operative variables were correlated with morbidity, mortality, and success in providing symptomatic relief. RESULTS: A total of 60 cases and 75 colon and rectal lesions were analyzed. After surgery, the morbidity rate was 65 percent, and the mortality was 6.7 percent. A successful outcome in providing symptomatic relief was achieved in 71.7 percent of cases. When comparing success after operations for the different lesions (stricture, 78.1 percent; hemorrhage, 64.3 percent; perforation, 100 percent; and fistula, 54.5 percent), the presence of a fistula was associated with symptomatic relief significantly less often than the remainder (P = 0.03). The type of operation had no effect on success rate: 72 percent for diversion, 66.7 percent for resection, and 83.3 percent for bypass. Morbidity and mortality rates were not significantly influenced by site of lesions, type of lesions, or choice of surgical operation. A permanent stoma was necessary in 70 percent of patients. CONCLUSIONS: The morbidity for surgical treatment of large bowel radiation injury is substantial, and largely unrelated to the type and location of the radiation lesion, as well as the type of operation. Success rates are reasonably high, but worst after fistula repair. The selection of therapy (medical, endoscopic, surgical) for radiation-induced colorectal lesions must take into account numerous factors and be highly individualized. C1 BROWN UNIV,PROVIDENCE,RI 02912. RHODE ISL HOSP,DEPT SURG,PROVIDENCE,RI 02902. HARVARD UNIV,SCH MED,DEPT SURG,SURG SERV,BOSTON,MA 02115. RP PRICOLO, VE (reprint author), MASSACHUSETTS GEN HOSP,SURG SERV,BOSTON,MA 02114, USA. NR 28 TC 18 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD JUL PY 1994 VL 37 IS 7 BP 675 EP 684 DI 10.1007/BF02054411 PG 10 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA NV870 UT WOS:A1994NV87000007 PM 8026234 ER PT J AU HU, ED MUELLER, E OLIVIERO, S PAPAIOANNOU, VE JOHNSON, R SPIEGELMAN, BM AF HU, ED MUELLER, E OLIVIERO, S PAPAIOANNOU, VE JOHNSON, R SPIEGELMAN, BM TI TARGETED DISRUPTION OF THE C-FOS GENE DEMONSTRATES C-FOS-DEPENDENT AND C-FOS-INDEPENDENT PATHWAYS FOR GENE-EXPRESSION STIMULATED BY GROWTH-FACTORS OR ONCOGENES SO EMBO JOURNAL LA English DT Article DE AP-1 FACTORS; C-FOS; C-FOS-DEFICIENT CELLS; METALLOPROTEASE; ONCOGENES ID IMMEDIATE-EARLY GENE; TRANSCRIPTIONAL ACTIVATION; PROTO-ONCOGENE; MESSENGER-RNA; CELLULAR-TRANSFORMATION; MOLECULAR-CLONING; NEGATIVE REGULATION; BASAL EXPRESSION; STROMELYSIN GENE; TRANSGENIC MICE AB The c-fos proto-oncogene is believed to play a pivotal role in transducing growth factor-mediated signals from the extracellular milieu into the nucleus. c-fos protein dimerizes with c-jun and related proteins and mediates transcription via AP-1 sites. Using c-fos-deficient mice generated through gene knockout techniques, we derived 3T3-type cell lines from primary embryonic fibroblasts. The c-fos-deficient cells grow normally under optimal culture conditions and show only a slight reduction in growth rate in low serum culture compared with control cells. They also express mRNA for most of the Fos and Jun family members at normal levels. The overall levels of AP-1 DNA binding activity are normal and several genes (c-jun, MCP1, metallothionein) known to contain functional AP-1 sites are expressed normally in the c-fos-deficient and control cells. In contrast, mRNA for the metalloproteases stromelysin (MMP-3) and type I collagenase (MMP-1), which are often induced by oncogenes and growth factors and have been implicated in tumor invasiveness, cannot be induced by epidermal growth factor or platelet-derived growth factor in c-fos-deficient cells. Transformation of mutant cells with polyoma middle T oncogene essentially restores wildtype levels of stromelysin expression, while transformation with v-src leads to only a weak induction of the metalloprotease. These results clearly demonstrate that some AP-1-dependent genes require c-fos for full expression while others do not; oncogenes may activate expression of metalloproteases via either fos-dependent or fos-independent mechanisms. These results also imply that c-fos may play an important regulatory role in the invasive behavior of malignant tumors, independent of any role this proto-oncogene might play in cell growth per se. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV SIENA,DIPARTIMENTO BIOL MOLEC,SEZ MICROBIOL,I-53100 SIENA,ITALY. UNIV PADUA,DIPARTIMENTO BIOL,I-35121 PADUA,ITALY. COLUMBIA UNIV,COLL PHYS & SURG,DEPT GENET & DEV,NEW YORK,NY 10032. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,HORMONE RES INST,SAN FRANCISCO,CA 94143. NR 88 TC 146 Z9 148 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 JUL 1 PY 1994 VL 13 IS 13 BP 3094 EP 3103 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NW771 UT WOS:A1994NW77100016 PM 8039503 ER PT J AU LEECH, CA HOLZ, GG HABENER, JF AF LEECH, CA HOLZ, GG HABENER, JF TI VOLTAGE-INDEPENDENT CALCIUM CHANNELS MEDIATE SLOW OSCILLATIONS OF CYTOSOLIC CALCIUM THAT ARE GLUCOSE-DEPENDENT IN PANCREATIC BETA-CELLS SO ENDOCRINOLOGY LA English DT Article ID CYCLIC ADP-RIBOSE; INSULIN-SECRETION; CYTOPLASMIC CA2+; IONIC CURRENTS; B-CELLS; CA-2+; ISLETS; RELEASE; ACTIVATION; LANGERHANS AB Pancreatic beta-cells and HIT-T15 cells exhibit oscillations of cytosolic calcium ([Ca2+](i)) that are dependent on glucose metabolism and appear to trigger pulsatile insulin secretion. Significantly, differences in the pattern of this [Ca2+](i) oscillatory activity may have important implications for our understanding of how glucose homeostasis is achieved during the feeding and fasting states. When single beta-cells are exposed to a stepwise increase in glucose concentration that mimics the transition from fasting to feeding states, fast irregular oscillations of [Ca2+](i) are observed. Alternatively, when single beta-cells are equilibrated in a steady state concentration of glucose that mimics the fasting state, slow periodic oscillations of [Ca2+](i) are noted. Here we report a fundamental difference in the mechanism by which glucose induces these two types of [Ca2+](i) oscillatory activity. In agreement with previous studies, we substantiate a role for L-type voltage-dependent Ca2+ channels as mediators of the fast oscillations of [Ca2+](i) observed after a stepwise increase in glucose concentration. In marked contrast, we report that voltage-independent calcium channels (VICCs) mediate slow oscillations of [Ca2+](i) that occur when beta-cells are equilibrated in steady state concentrations of glucose. Slow [Ca2+](i) oscillations are mediated by VICCs which are pharmacologically and biophysically distinguishable from voltage-dependent Ca2+ channels that mediate fast oscillations. Specifically, slow [Ca2+](i) oscillations are blocked by extracellular La3+, but not by nifedipine, and are independent of changes in membrane potential. Measurements of membrane conductance also indicate an important role for VICCs, as demonstrated by a steady state inward Ca2+ current that is blocked by La3+. The steady state Ca2+ current appears to generate slow [Ca2+](i) oscillations by triggering Ca2+-induced Ca2+ release from intracellular Ca2+ stores, a process that is mimicked by extracellular application of caffeine, a sensitizer of the ryanodine receptor/Ca2+ release channel. Depletion of intracellular Ca2+ stores with thapsigargin stimulated Mn2+ influx, suggesting the presence of Ca2+-release-activated Ca2+ channels. Taken together, these observations are consistent with a role for VICCs (possibly G-type channels) and/or Ca2+-release-activated Ca2+ channels as mediators of slow [Ca2+](i) oscillations in beta-cells. We propose that slow oscillations of [Ca2+](i) probably serve as important initiators of insulin secretion under conditions in which tight control of glucose homeostasis is necessary, as is the case during the fasting normoglycemic state. RP LEECH, CA (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, HOWARD HUGHES MED INST, MOLEC ENDOCRINOL LAB, BOSTON, MA 02114 USA. RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [DK-30834, R01 DK045817, DK-30457, R01 DK030834, R01 DK045817-06A2, DK-45817] NR 36 TC 41 Z9 41 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1994 VL 135 IS 1 BP 365 EP 372 DI 10.1210/en.135.1.365 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU811 UT WOS:A1994NU81100050 PM 8013370 ER PT J AU OCONNELL, NA KUMAR, A CHATZIPANTELI, K MOHAN, A AGARWAL, RK HEAD, C BORNSTEIN, SR ABOUSAMRA, AB GWOSDOW, AR AF OCONNELL, NA KUMAR, A CHATZIPANTELI, K MOHAN, A AGARWAL, RK HEAD, C BORNSTEIN, SR ABOUSAMRA, AB GWOSDOW, AR TI INTERLEUKIN-1 REGULATES CORTICOSTERONE SECRETION FROM THE RAT ADRENAL-GLAND THROUGH A CATECHOLAMINE-DEPENDENT AND PROSTAGLANDIN E(2)-INDEPENDENT MECHANISM SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; CHROMAFFIN CELLS; SIGNAL TRANSDUCTION; PITUITARY-CELLS; PHOSPHORYLATION; STIMULATION; PATHWAYS; INVITRO; CORTEX AB Studies from this and other laboratories have shown that interleukin-1 alpha (IL-1 alpha) stimulates corticosterone and prostaglandin (PG) release from primary cultures of rat adrenal cells. A previous report from our laboratory (1) indicated involvement of the alpha-adrenergic system in IL-1 alpha-stimulated corticosterone secretion from primary cultures of rat adrenal cells. The present experiments were conducted to determine the role of catecholamines and eicosanoids in IL-1-stimulated corticosterone release from primary rat adrenal cells. Primary adrenal cells were incubated for 24 h at 37 C with IL-1 alpha (10 nM), medium, or the appropriate agonist. After incubation, the supernatant was removed and assayed for epinephrine, prostaglandin E(2) (PGE(2)), and corticosterone concentrations. At this time, untreated adrenal cells were fixed for immunohistochemical staining with a specific antirat tyrosine hydroxylase antibody. The results indicate that the primary adrenal cells contained 3.1 +/- 0.45% tyrosine hydroxylase-positive cells. On the ultrastructural level, the chromaffin cells were found to be in direct cellular contact with cortical cells. IL-1 alpha significantly increased (P < 0.05) epinephrine, PGE(2), and corticosterone levels above those in medium-treated controls from primary adrenal cells. In the presence of the alpha-adrenergic antagonist phentolamine (10 mu M), IL-1 alpha-stimulated (P < 0.05) corticosterone release was inhibited, whereas IL-1 alpha-induced PGE(2) release was not affected. Conversely, the presence of the cyclooxygenase inhibitor indomethacin (10 mu M) significantly inhibited IL-1 alpha-induced PGE(2) secretion without altering the effect of IL-1 alpha on corticosterone release. Inhibitors of the 5-lipoxygenase system (10 mu M CGS 8518) and the lipoxygenase and cytochrome P450 monooxygenase systems (10 mu M nordihydroguaiaretic acid) did not effect IL-1 alpha-induced corticosterone or PGE(2) release. These observations indicate that IL-1 alpha stimulates corticosterone release through an alpha-adrenergic mechanism that is independent of PGE(2) release from primary rat adrenal cells. C1 MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. TUFTS UNIV, SCH VET MED, N GRAFTON, MA 01536 USA. UNIV ULM, ULM, GERMANY. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [NIDDK DK-41419] NR 28 TC 47 Z9 47 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1994 VL 135 IS 1 BP 460 EP 467 DI 10.1210/en.135.1.460 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU811 UT WOS:A1994NU81100062 PM 8013385 ER PT J AU HAYES, GB YE, TT LU, PL DAI, HL CHRISTIANI, DC AF HAYES, GB YE, TT LU, PL DAI, HL CHRISTIANI, DC TI RESPIRATORY-DISEASE IN COTTON TEXTILE WORKERS - EPIDEMIOLOGIC ASSESSMENT OF SMALL AIRWAY FUNCTION SO ENVIRONMENTAL RESEARCH LA English DT Article ID REPUBLIC-OF-CHINA; LUNG-FUNCTION; PULMONARY-FUNCTION; DUST; BYSSINOSIS; MILLS; ENDOTOXIN AB We performed a cross-sectional study of 705 textile workers in two cotton mills and one silk mill in Shanghai, People's Republic of China, to assess small airway function among cotton textile workers and to compare the FEV, to the FEF(25-75) in detecting airflow obstruction in these workers. All workers had at least 2 years of work experience. Environmental sampling was performed with vertical elutriators and revealed that in the cotton mills mean elutriated dust levels were 1.07 +/- 0.23 mg/m(3) in mill 1 and 1.01 mg/m(3) +/- 2.4 mg/m(3) in mill 2. Mean endotoxin levels were 332 +/- 83 ng/m(3) in mill 1 and 101 +/- 46 ng/m(3) in mill 2. No differences were found in preshift FEV(1) or FEF(25-75) between cotton and silk workers. Cotton workers had significantly greater declines than silk workers in FEV, across a workshift, but not in FEF(25-75). These acute changes in FEV, were noted in both byssinotic and nonbyssinotic workers. Although cotton dust may affect both large and small airways, spirometric measures of small airway function (e.g., FEF(25-75)) add little to the FEV, and FVC in detecting airflow limitation in cotton dust-exposed workers. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PULM CRIT CARE UNIT,BOSTON,MA 02115. SHANGHAI FIRST MED COLL,DEPT OCCUPAT HLTH,SHANGHAI,PEOPLES R CHINA. FIRST TEXT HOSP,SHANGHAI TEXT BUR,SHANGHAI,PEOPLES R CHINA. FU NHLBI NIH HHS [HL-07354]; NIEHS NIH HHS [ES00002]; PHS HHS [R010H02421] NR 30 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JUL PY 1994 VL 66 IS 1 BP 31 EP 43 DI 10.1006/enrs.1994.1042 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA NV450 UT WOS:A1994NV45000003 PM 8013436 ER PT J AU HANDFORTH, A CHENG, JT MANDELKERN, MA TREIMAN, DM AF HANDFORTH, A CHENG, JT MANDELKERN, MA TREIMAN, DM TI MARKEDLY INCREASED MESIOTEMPORAL LOBE METABOLISM IN A EASE WITH PLEDS - FURTHER EVIDENCE THAT PLEDS ARE A MANIFESTATION OF PARTIAL STATUS EPILEPTICUS SO EPILEPSIA LA English DT Article DE STATUS EPILEPTICUS; ELECTROENCEPHALOGRAPHY; PARTIAL SEIZURES; POSITRON EMISSION TOMOGRAPHY; TEMPORAL LOBE ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; COMPLEX PARTIAL SEIZURES; CLINICAL-SIGNIFICANCE; F-18 FLUORODEOXYGLUCOSE; PARTIAL EPILEPSY; DISCHARGES; EEG; SPECT AB The pathophysiologic and clinical significance of periodic lateralized epileptiform discharges (PLEDs) is unclear; whether PLEDs represent an ictal condition that should be treated remains uncertain. We performed FDG-positron emission computed tomography (FDG-PET) in a patient with PLEDs at 3 days, 18 days, and 10 weeks after onset. During left temporal PLEDs, the initial scan showed intense hypermetabolism of the left mesiotemporal region. The second scan, performed when PLEDs were resolving, displayed reduced hypermetabolism. The follow-up scan, when PLEDs had resolved, showed left temporal hypometabolism. These findings, together with clinical evidence from the literature, are compatible with the interpretation that PLEDs represent partial status epilepticus (SE); whether vigorous therapy is required to prevent neuronal damage from this focal seizure activity remains uncertain. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF IRVINE,DEPT PHYS,IRVINE,CA 92717. RP HANDFORTH, A (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,WADSWORTH DIV,WILSHIRE & SAWTELLE BLVDS,LOS ANGELES,CA 90073, USA. NR 33 TC 93 Z9 93 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL-AUG PY 1994 VL 35 IS 4 BP 876 EP 881 DI 10.1111/j.1528-1157.1994.tb02526.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA PF808 UT WOS:A1994PF80800027 PM 8082637 ER PT J AU TOGAWA, K JASKIEWICZ, K TAKAHASHI, H MELTZER, SJ RUSTGI, AK AF TOGAWA, K JASKIEWICZ, K TAKAHASHI, H MELTZER, SJ RUSTGI, AK TI HUMAN PAPILLOMAVIRUS DNA-SEQUENCES IN ESOPHAGUS SQUAMOUS-CELL CARCINOMA SO GASTROENTEROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; PRECANCEROUS LESIONS; INSITU HYBRIDIZATION; RETINOBLASTOMA GENES; REACTION PRODUCTS; E6 ONCOPROTEIN; RAS MUTATIONS; MYC GENES; WILD-TYPE; P53 GENE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GASTROINTESTINAL UNIT,BOSTON,MA. UNIV CAPE TOWN,SCH MED,DEPT ANAT PATHOL,CAPE TOWN 7925,SOUTH AFRICA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,CTR CANC,SCH MED,BOSTON,MA. UNIV MARYLAND,SCH MED,DIV GASTROENTEROL,BALTIMORE,MD 21201. NR 49 TC 80 Z9 84 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1994 VL 107 IS 1 BP 128 EP 136 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NV981 UT WOS:A1994NV98100017 PM 7912679 ER PT J AU WARSHAW, AL RATTNER, DW FERNADEZDELCASTILLO, C AF WARSHAW, AL RATTNER, DW FERNADEZDELCASTILLO, C TI INTRAVENOUS CONTRAST DOES AGGRAVATE EXPERIMENTAL PANCREATITIS SO GASTROENTEROLOGY LA English DT Letter RP WARSHAW, AL (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1994 VL 107 IS 1 BP 320 EP 321 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NV981 UT WOS:A1994NV98100040 PM 8020683 ER PT J AU WARSHAW, AL RATTNER, DW FERNANDEZDELCASTILLO, C AF WARSHAW, AL RATTNER, DW FERNANDEZDELCASTILLO, C TI CONTRAST-MEDIUM WORSENS PANCREATITIS - REPLY SO GASTROENTEROLOGY LA English DT Letter RP WARSHAW, AL (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1994 VL 107 IS 1 BP 322 EP 322 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NV981 UT WOS:A1994NV98100042 ER PT J AU RANDALL, GM JENSEN, DM MACHICADO, GA HIRABAYASHI, K JENSEN, ME YOU, S PELAYO, E AF RANDALL, GM JENSEN, DM MACHICADO, GA HIRABAYASHI, K JENSEN, ME YOU, S PELAYO, E TI PROSPECTIVE RANDOMIZED COMPARATIVE-STUDY OF BIPOLAR VERSUS DIRECT-CURRENT ELECTROCOAGULATION FOR TREATMENT OF BLEEDING INTERNAL HEMORRHOIDS SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID DIRECT-CURRENT ELECTROTHERAPY AB Internal hemorrhoids are the most common cause of lower gastrointestinal bleeding. Although new anoscopic therapies are available, few comparative randomized studies have evaluated them in regard to long-term efficacy, recurrence rates, and safety. Our purpose was to compare the treatment of internal hemorrhoids with direct current (Ultroid, Cabot Medical, Langhorn, Pa.) and bipolar (BICAP, Circon ACMI, Stamford, Conn.) hemorrhoid probes. One hundred patients with symptomatic internal hemorrhoids were randomized: 50 to direct current electrocoagulation and 50 to bipolar electrocoagulation. Follow-up and treatment were at 3- to 4-weekly intervals; two to three hemorrhoid segments were treated at each session until relief of symptoms (bleeding, prolapse, and discharge) and a reduction in hemorrhoid size to grade 1 or 0 were noted. The hemorrhoids of 98% of all patients studied were grade 2 or 3; 2% of patients had grade 1 hemorrhoids and none had grade 4 hemorrhoids. At 1 year after treatment, most patients had no (69%) or only mild (23%) recurrence, and a few had severe, symptomatic (8%) hemorrhoid recurrence. A greater recurrence rate was noted after direct current treatment (34%) than bipolar treatment (29%). In contrast, rebleeding at 1 year occurred less frequently after direct current treatment (5%) than after bipolar treatment (20%). Our conclusions were as follows: (1) Both direct current and bipolar probes were effective for control of chronic bleeding from grade 1 to 3 internal hemorrhoids. (2) Bipolar probe was significantly faster than direct current probe. (3) Direct current treatment produced fewer complications than bipolar treatment (12% versus 14%). (4) Recurrence rates were low after 1 year with either device (8%). (5) More recurrences were noted after direct current electrocoagulation (34%) than after bipolar electrocoagulation (29%). C1 UNIV CALIF LOS ANGELES,CTR ULCER RES & EDUC,W LOS ANGELES VET ADM,LOS ANGELES,CA 90024. VALLEY MED CTR,LOS ANGELES,CA. FU NIDDK NIH HHS [NIDDK 41301] NR 17 TC 25 Z9 29 U1 2 U2 5 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL-AUG PY 1994 VL 40 IS 4 BP 403 EP 410 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NY866 UT WOS:A1994NY86600001 PM 7926528 ER PT J AU ROSENSTEIN, M WEBSTER, EW AF ROSENSTEIN, M WEBSTER, EW TI EFFECTIVE DOSE TO PERSONNEL WEARING PROTECTIVE APRONS DURING FLUOROSCOPY AND INTERVENTIONAL RADIOLOGY SO HEALTH PHYSICS LA English DT Letter C1 MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. RP ROSENSTEIN, M (reprint author), CTR DEVICES & RADIOL HLTH, OFF HLTH PHYS, ROCKVILLE, MD 20850 USA. NR 8 TC 34 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 1994 VL 67 IS 1 BP 88 EP 89 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA NT232 UT WOS:A1994NT23200012 PM 8200807 ER PT J AU SUSTER, S WONG, TY AF SUSTER, S WONG, TY TI POLYMORPHOUS SWEAT GLAND CARCINOMA SO HISTOPATHOLOGY LA English DT Article DE SWEAT GLAND CARCINOMA; SKIN ADNEXAL NEOPLASMS; ECCRINE CARCINOMA ID ADENOID CYSTIC CARCINOMA; MICROCYSTIC ADNEXAL CARCINOMA; SALIVARY-GLANDS; SKIN; DIFFERENTIATION; ADENOCARCINOMA; TUMORS; BREAST AB We describe nine cases of a distinctive cutaneous neoplasm showing features of eccrine adnexal differentiation that were characterized by their variegated histological appearance and low-grade malignant behaviour. The term polymorphous sweat gland carcinoma is proposed to designate these lesions. The tumours presented as large, long-standing, slow growing, dermal nodules showing a marked predilection for the extremities. Six patients were women. The patients were aged 42-70 years (mean, 59.8 years). Histologically, the lesions were characterized by a highly cellular proliferation displaying a variety of growth patterns, including solid, trabecular, tubular, pseudopapillary and cylindromatous, with prominent stromal changes including haemorrhage, hyalinization and cystic change, and displaying moderate cytological atypia and mitoses. Focal areas showing features associated with eccrine differentiation (i.e. tubular structures, small glandular lumina) could be identified in all cases. Clinical follow-up in six cases showed that two of the lesions recurred locally over a period of 3-6 years, and one tumour metastasized to regional lymph nodes 3 years after excision. Polymorphous sweat gland carcinoma should be considered in the differential diagnosis of neoplastic epithelial dermal proliferations; complete but conservative surgical excision appears to be the treatment of choice for these lesions. C1 UNIV MIAMI,SCH MED,MIAMI,FL. MASSACHUSETTS GEN HOSP,DIV DERMATOPATHOL,BOSTON,MA 02114. MT SINAI MED CTR,ARKADI M RYWLIN DEPT PATHOL & LAB MED,MIAMI,FL. HARVARD UNIV,SCH MED,BOSTON,MA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD JUL PY 1994 VL 25 IS 1 BP 31 EP 39 DI 10.1111/j.1365-2559.1994.tb00595.x PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA NY299 UT WOS:A1994NY29900003 PM 7959643 ER PT J AU GARZATREVINO, ES AF GARZATREVINO, ES TI NEUROBIOLOGICAL FACTORS IN AGGRESSIVE-BEHAVIOR SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Review ID IMPULSIVE FIRE SETTERS; CEREBROSPINAL-FLUID; MONOAMINE METABOLITES; VIOLENT OFFENDERS; BRAIN-SEROTONIN; FAMILY HISTORY; CSF 5-HIAA; SUICIDE; ILLNESS; IMPAIRMENT AB The author's aim was to review literature in the neurosciences and psychiatric clinical research reports about biological factors in aggression and the pathophysiological mechanisms that accompany aggression in neuropsychiatric syndromes. Method: Studies were located through computer searches of relevant experimental reports and review articles mainly from the last 25 years. Results: Several studies using neuroimaging and neurophysiological and neuropathological research techniques have identified lesions in the limbic structures, temporal lobes, and frontal lobes of the brain in abnormally aggressive individuals. Several reports have associated deficiency or dysregulation of serotonin with homicidal, suicidal, and impulsive behavior. However, few studies have focused on polypeptides or second messenger systems, although abnormalities in these systems have been reported in patients with neuropsychiatric syndromes who have shown aggressive behavior. Even fewer studies focus on the correlation of brain structures and metabolic markers. Conclusions: The understanding of aggressive behavior in psychiatric patients is fragmented. Some explanations are speculative and extrapolated to clinical psychiatric syndromes from experimental data on the neurophysiology of cats, rats, and other mammals. Identification of biochemical markers that can be used in predicting patients' response to pharmacological interventions may be the next step in developing more rational treatment of violent patients. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP GARZATREVINO, ES (reprint author), UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284, USA. NR 100 TC 27 Z9 29 U1 0 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD JUL PY 1994 VL 45 IS 7 BP 690 EP 699 PG 10 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA NU776 UT WOS:A1994NU77600011 PM 7927294 ER PT J AU NOVELLETTO, A PERSICHETTI, F SABBADINI, G MANDICH, P BELLONE, E AJMAR, F SQUITIERI, F CAMPANELLA, G BOZZA, A MACDONALD, ME GUSELLA, JF FRONTALI, M AF NOVELLETTO, A PERSICHETTI, F SABBADINI, G MANDICH, P BELLONE, E AJMAR, F SQUITIERI, F CAMPANELLA, G BOZZA, A MACDONALD, ME GUSELLA, JF FRONTALI, M TI POLYMORPHISM ANALYSIS OF THE HUNTINGTIN GENE IN ITALIAN FAMILIES AFFECTED WITH HUNTINGTON DISEASE SO HUMAN MOLECULAR GENETICS LA English DT Article ID AGE-OF-ONSET; TRINUCLEOTIDE REPEAT; REGION AB Two sources of variation in the huntingtin gene, the length of the COO-rich segment downstream to the (CAG)(n) stretch undergoing expansion in Huntington disease (HD) and the deletion of 3 bp at codon positions 2642 - 2645 (Delta 2642), were analysed on the normal and HD chromosomes of 80 Italian families affected with HD. No instances of meiotic instability of the CCG-rich segment were detected. A strong linkage disequilibrium was found between the HD mutation and alleles at both polymorphic regions: CCG-rich length alleles different from 176 bp are underrepresented while Delta 2642 is overrepresented on HD chromosomes. The presence of such alleles on HD chromosomes does not affect age at onset of the disease. Normal chromosomes displayed a non-random association, shorter (CAG)(n) segments being preferentially followed by longer CCG-rich segments. Finally, the finding, among normal subjects, of carriers of variants on both chromosomes denotes that variation at either of the two polymorphisms does not impair the function of the huntingtin gene product. C1 CNR,IST MED SPERIMENTALE,I-00137 ROME,ITALY. UNIV GENOA,IST BIOL & GENET,I-16132 GENOA,ITALY. UNIV NAPLES,NEUROL CLIN 2,I-80131 NAPLES,ITALY. UNIV FERRARA,IST CHIM BIOL,I-44100 FERRARA,ITALY. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET LAB,BOSTON,MA 02114. RP NOVELLETTO, A (reprint author), UNIV ROMA TOR VERGATA,DIPARTIMENTO BIOL,VIA E CARNEVALE,I-00173 ROME,ITALY. OI Novelletto, Andrea/0000-0002-1146-7680; Squitieri, Ferdinando /0000-0002-7397-1727 FU Telethon [E.0087] NR 12 TC 29 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1994 VL 3 IS 7 BP 1129 EP 1132 DI 10.1093/hmg/3.7.1129 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NX341 UT WOS:A1994NX34100015 PM 7981682 ER PT J AU SCHIPANI, E HUSTMYER, FG BERGWITZ, C JUPPNER, H AF SCHIPANI, E HUSTMYER, FG BERGWITZ, C JUPPNER, H TI POLYMORPHISM IN EXON-M7 OF THE PTHR GENE SO HUMAN MOLECULAR GENETICS LA English DT Note ID RECEPTOR C1 MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,ENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. INDIANA UNIV,DEPT MED,INDIANAPOLIS,IN 46202. FU NIDDK NIH HHS [DK 46718-01] NR 4 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1994 VL 3 IS 7 BP 1210 EP 1210 DI 10.1093/hmg/3.7.1210-a PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NX341 UT WOS:A1994NX34100045 PM 7981709 ER PT J AU BOUFFARD, D DUNCAN, LM HOWARD, CA MIHM, MC BYERS, HR AF BOUFFARD, D DUNCAN, LM HOWARD, CA MIHM, MC BYERS, HR TI ACTIN-BINDING PROTEIN EXPRESSION IN BENIGN AND MALIGNANT MELANOCYTIC PROLIFERATIONS SO HUMAN PATHOLOGY LA English DT Article DE MELANOMA; NEVUS; ACTIN-BINDING PROTEIN; MIGRATION ID CELL MOTILITY; EXTRACELLULAR-MATRIX; TUMOR PROGRESSION; FOCAL ADHESIONS; ALPHA-ACTININ; CD44; HYALURONATE; METASTASIS; MOLECULES; MIGRATION C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,DIV DERMATOPATHOL,BOSTON,MA. RI Duncan, Lyn/E-9878-2013 NR 43 TC 22 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 1994 VL 25 IS 7 BP 709 EP 714 DI 10.1016/0046-8177(94)90305-0 PG 6 WC Pathology SC Pathology GA NX227 UT WOS:A1994NX22700013 PM 8026830 ER PT J AU HUMPHREYS, T REINHERZ, EL AF HUMPHREYS, T REINHERZ, EL TI INVERTEBRATE IMMUNE RECOGNITION, NATURAL IMMUNITY AND THE EVOLUTION OF POSITIVE SELECTION SO IMMUNOLOGY TODAY LA English DT Article ID CELL ANTIGEN RECEPTOR; MHC MOLECULES; KILLER-CELLS; T-CELLS; SELF; HISTOCOMPATIBILITY; RESPONSES; GENETICS; COMPLEX; SYSTEM AB Invertebrate immunity exhibits immediate recognition without prior contact. Here, Tom Humphreys and Ellis Reinherz propose that receptors capable of actively recognizing self histocompatibility antigens could be generated by a process similar to positive selection, and that these could guide 'natural immunity' to foreign cells. These ideas provide a conceptual basis for invertebrate immunity and for understanding the evolutionary precedents for T-cell-mediated antigen recognition. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. RP HUMPHREYS, T (reprint author), UNIV HAWAII,KEWALO MARINE LAB,41 AHUI ST,HONOLULU,HI 96822, USA. NR 30 TC 55 Z9 57 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JUL PY 1994 VL 15 IS 7 BP 316 EP 320 DI 10.1016/0167-5699(94)90079-5 PG 5 WC Immunology SC Immunology GA NV213 UT WOS:A1994NV21300006 PM 8086100 ER PT J AU JUNE, CH BLUESTONE, JA NADLER, LM THOMPSON, CB AF JUNE, CH BLUESTONE, JA NADLER, LM THOMPSON, CB TI THE B7 AND CD28 RECEPTOR FAMILIES SO IMMUNOLOGY TODAY LA English DT Review ID T-CELL ACTIVATION; CTLA-4 COUNTER-RECEPTOR; IL-2 GENE-EXPRESSION; HUMAN LYMPHOCYTES-T; PROTEIN-KINASE-C; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; CYCLOSPORINE-A; MESSENGER-RNA; TYROSINE PHOSPHORYLATION AB Current evidence suggests that T-cell receptor (TCR) recognition of antigen bound to the major histocompatibility complex (Ag-MHC) is insufficient to lead to T-cell proliferation or effector function. For a helper T cell to produce sufficient interleukin 2 (IL-2) to allow autocrine-driven clonal expansion, there is a requirement for so-called 'co-stimulatory' or 'accessory' signals in addition to TCR ligation by Ag-MHC. The interaction of the CD28 receptor on T cells with B7 on antigen-presenting cells (APCs) supplies one such co-stimulatory signal. However, the recent discovery that CD28 and B7 are each members of larger gene families suggests that the regulation of co-stimulation is more complex than previously imagined. Here, Carl June and colleagues highlight recent advances in the understanding of the CD28 and B7 receptor families. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. UNIV CHICAGO,BEN MAY INST,DEPT PATHOL,COMM IMMUNOL,CHICAGO,IL 60637. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL,BOSTON,MA 02115. UNIV CHICAGO,HOWARD HUGHES MED INST,CHICAGO,IL 60637. UNIV CHICAGO,DEPT MED,CHICAGO,IL 60637. UNIV CHICAGO,DEPT MOLEC GENET & CELL BIOL,CHICAGO,IL 60637. RP JUNE, CH (reprint author), USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889, USA. NR 93 TC 1307 Z9 1340 U1 2 U2 29 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JUL PY 1994 VL 15 IS 7 BP 321 EP 331 DI 10.1016/0167-5699(94)90080-9 PG 11 WC Immunology SC Immunology GA NV213 UT WOS:A1994NV21300007 PM 7522010 ER PT J AU CHAMPION, CI BLANCO, DR SKARE, JT HAAKE, DA GILADI, M FOLEY, D MILLER, JN LOVETT, MA AF CHAMPION, CI BLANCO, DR SKARE, JT HAAKE, DA GILADI, M FOLEY, D MILLER, JN LOVETT, MA TI A 9.0-KILOBASE-PAIR CIRCULAR PLASMID OF BORRELIA-BURGDORFERI ENCODES AN EXPORTED PROTEIN - EVIDENCE FOR EXPRESSION ONLY DURING INFECTION SO INFECTION AND IMMUNITY LA English DT Article ID PHOSPHATE-BINDING PROTEIN; LYME-DISEASE SPIROCHETE; OUTER-MEMBRANE PROTEINS; ESCHERICHIA-COLI; MOLECULAR-CLONING; LINEAR-PLASMID; ALKALINE-PHOSPHATASE; SEQUENCE-ANALYSIS; SIGNAL PEPTIDES; SALMONELLA-TYPHIMURIUM AB In this study, we report the cloning, sequencing, and molecular analysis of a gene located on a 9.0-kbp circular plasmid of virulent Borrelia burgdorferi B31 designated eppA (exported plasmid protein A). This gene encodes a precursor protein of 174 amino acids including a signal peptide of 20 amino acids and a type I signal peptidase cleavage site. The mature EppA protein of 154 amino acids has a calculated molecular weight of 17,972. Several lines of evidence suggest that eppA is not expressed by B. burgdorferi B31 during in vitro cultivation. Immunoblot analysis using hyperimmune rabbit antiserum to recombinant EppA (rEppA) did not detect the presence of EppA in B. burgdorferi B31 cultivated in vitro. Northern blot analysis using total RNA isolated from in vitro cultivated virulent B. burgdorferi B31 failed to detect an eppA transcript. EppA was not detected in culture supernatants of virulent B. burgdorferi B31 in 9 sensitive antigen-capture enzyme-linked immunosorbent assay. In contrast, evidence for expression of eppA during infection,vas based on the observation that patients with Lyme disease as well as rabbits experimentally infected with B. burgdorferi B31 produced antibodies that recognized rEppA. Because the cellular location of EppA in B. burgdorferi cannot be determined in vivo because of very small numbers of organisms present in vertebrate infection, we examined the cellular location of rEppA expressed in Escherichia coli. In E. coli, rEppA is targeted to the outer membrane. In addition, purified E. coli outer membranes containing rEppA treated with chaotrophic agents did not result in rEppA release. These findings are consistent with the idea that EppA is not peripherally associated with the outer membrane of E. coli but rather has an integral outer membrane association. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,DIV INFECT DIS,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DIV INFECT DIS,LOS ANGELES,CA 90073. RP CHAMPION, CI (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024, USA. FU NIAID NIH HHS [5-T32-AI07323, AI-21352, AI-29733] NR 59 TC 101 Z9 101 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 JUL PY 1994 VL 62 IS 7 BP 2653 EP 2661 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NU014 UT WOS:A1994NU01400001 PM 8005657 ER PT J AU JUPITER, JB MULLAJI, AB AF JUPITER, JB MULLAJI, AB TI BLADE PLATE FIXATION OF PROXIMAL HUMERAL NON-UNIONS SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article AB Non-union of fracture of the proximal humerus is unusual and can be difficult to treat. It is found more often than not in the elderly patient with weak bone, resorption at the fracture site, contracture of the glenohumeral joint and associated medical conditions. A blade plate, designed specifically for the treatment of these non-unions, was used in nine patients - seven females and two males (mean age 66 years) - who had painful non-union with a mean duration of 22.5 months. Autologous bone grafting was used in all cases. Eight non-unions followed displaced two-part proximal humeral fractures: five had been initially treated conservatively and four with medullary nails. Five patients had associated medical illness. After a mean of 6.5 months (range 4-28 months), union had been achieved in all but one patient. Functional evaluation revealed good results in five patients, fair results in three and one poor result. Use of the blade plate offered a successful method of stable internal fixation in these complex cases. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 38 Z9 40 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD JUL PY 1994 VL 25 IS 5 BP 301 EP 303 DI 10.1016/0020-1383(94)90240-2 PG 3 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA NP473 UT WOS:A1994NP47300005 PM 8034347 ER PT J AU SHINKAI, Y ALT, FW AF SHINKAI, Y ALT, FW TI CD3-EPSILON-MEDIATED SIGNALS RESCUE THE DEVELOPMENT OF CD4+ CD8+ THYMOCYTES IN RAG-2(-/-) MICE IN THE ABSENCE OF TCR BETA-CHAIN EXPRESSION SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE GENE TARGETING MOUSE; IMMUNE DEFICIENT MOUSE; IMMATURE T-CELLS; SIGNAL TRANSDUCTION; THYMOCYTE DEVELOPMENT ID T-CELL-RECEPTOR; MONOCLONAL-ANTIBODIES; MUTANT MICE; B-CELLS; LACKING; ALPHA; REARRANGEMENT; GENE; DIFFERENTIATION; IDENTIFICATION AB Recent studies have shown that TCR beta chain expression can effect the differentiation of CD4-CD8- double-negative (DN) thymocytes to CD4+CD8+ double-positive (DP) thymocytes. The TCR beta chain is expressed on the surface of DP thymocytes in association with CD3gamma, delta and epsilon chains, suggesting a potential role for CD3 components in this signaling process. We now report detection of a very low level of surface expression of CD3epsilon on adult DN RAG-2-/- thymocytes. This surface CD3epsilon was associated with CD3gamma and delta chains, as detected by anti-CD3epsilon immunoprecipitation analyses. Significantly, injection of anti-CD3epsilon mAb into RAG-2-/- mice led to the accumulation of an IL-2Ralpha- CD2+ DP cell population and a nearly 100-fold increase in thymic cellularity to essentially normal levels. Together, these data strongly indicate that TCR beta chain-mediated developmental signals are transduced by CD3 components and provide potential insights into mechanisms by which TCR beta chain expression may effect this process. C1 CHILDRENS HOSP MED CTR,HOWARD HUGHES MED INST,300 LONGWOOD AVE,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT GENET,BOSTON,MA 02115. CHILDRENS HOSP MED CTR,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RI Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 FU NCI NIH HHS [CA42335]; NIAID NIH HHS [AI20047, U01 AI31541] NR 38 TC 184 Z9 184 U1 0 U2 1 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 JUL PY 1994 VL 6 IS 7 BP 995 EP 1001 DI 10.1093/intimm/6.7.995 PG 7 WC Immunology SC Immunology GA NY685 UT WOS:A1994NY68500009 PM 7947468 ER PT J AU MOMBAERTS, P MIZOGUCHI, E LJUNGGREN, HG IACOMINI, J ISHIKAWA, H WANG, L GRUSBY, MJ GLIMCHER, LH WINN, HJ BHAN, AK TONEGAWA, S AF MOMBAERTS, P MIZOGUCHI, E LJUNGGREN, HG IACOMINI, J ISHIKAWA, H WANG, L GRUSBY, MJ GLIMCHER, LH WINN, HJ BHAN, AK TONEGAWA, S TI PERIPHERAL LYMPHOID DEVELOPMENT AND FUNCTION IN TCR MUTANT MICE SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE GENE TARGETING; LYMPHOCYTES; MUTANT MICE; T-CELLS ID ANTIGEN RECEPTOR GENES; CLASS-II MOLECULES; DELTA-T-CELLS; ALPHA-BETA; V(D)J RECOMBINATION; LYMPHOCYTES-T; GENERATION; EXPRESSION; DEPLETION; RAG-1 AB We describe the development and function of the peripheral lymphoid system of mutant mice rendered deficient in either ce or gammadelta T cells via targeting of TCR genes in embryonic stem cells. in the spleen of alphabeta T cell-deficient mice, gammadelta T cells do not compensate in numbers for the lack of alphabeta T cells, but B cells do. Alphabeta T cell-deficient mice are unable to mount an antibody response to ovalbumin and do not reject skin allografts. Natural killer cell function is not impaired in any of the mutant mice. TCR mutant mice will prove useful in dissecting diffferential functions of alphabeta and gammadelta T cells in vivo. C1 MIT,CTR CANC RES,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. KAROLINSKA INST,DEPT MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT UNIT,BOSTON,MA 02114. NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. NR 29 TC 84 Z9 84 U1 1 U2 1 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 JUL PY 1994 VL 6 IS 7 BP 1061 EP 1070 DI 10.1093/intimm/6.7.1061 PG 10 WC Immunology SC Immunology GA NY685 UT WOS:A1994NY68500016 PM 7947457 ER PT J AU FERRY, JA YOUNG, RH ENGEL, G SCULLY, RE AF FERRY, JA YOUNG, RH ENGEL, G SCULLY, RE TI OXYPHILIC SERTOLI-CELL TUMOR OF THE OVARY - A REPORT OF 3 CASES, 2 IN PATIENTS WITH THE PEUTZ-JEGHERS SYNDROME SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE OVARY; SERTOLI CELL TUMOR; PEUTZ-JEGHERS SYNDROME (PJS); OXYPHIL ID SEX-CORD TUMOR; ADENOMA MALIGNUM; ANNULAR TUBULES; CERVIX AB Three women, aged 19, 21, and 30 years, two with the Peutz-Jeghers syndrome (PJS), had unilateral ovarian tumors composed of Sertoli cells with abundant eosinophilic cytoplasm. Electron microscopical and immunohistochemical examinations in one case supported the diagnosis of a sex cord tumor. Two patients are well 3 and 20 months postoperatively; the third was well for 15 years when recurrent tumor involving multiple intraabdominal sites was discovered. The occurrence of two of these tumors in patients with PJS and the known increased frequency of sex cord tumors in patients with this syndrome indicate an association. Sertoli cell tumor should be included in the differential diagnosis of oxyphilic ovarian tumors, particularly if there is a tubular pattern. C1 BELMONT COMMUNITY HOSP,DEPT PATHOL,CHICAGO,IL. RP FERRY, JA (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114, USA. NR 21 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JUL PY 1994 VL 13 IS 3 BP 259 EP 266 DI 10.1097/00004347-199407000-00010 PG 8 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA NR740 UT WOS:A1994NR74000010 PM 7523322 ER PT J AU WANG, CC EFIRD, JT AF WANG, CC EFIRD, JT TI DOES PROLONGED TREATMENT COURSE ADVERSELY AFFECT LOCAL-CONTROL OF CARCINOMA OF THE LARYNX SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT ASTRO 35th Annual Meeting CY OCT 11-15, 1993 CL NEW ORLEANS, LA SP AMER SOC THERAPEUT RADIOL & ONCOL DE RADIATION THERAPY TREATMENT COURSE; PROLONGED TREATMENT AND LOCAL CONTROL; LARYNGEAL CARCINOMA ID SQUAMOUS-CELL CARCINOMA; DAY RADIATION-THERAPY; SUPRAGLOTTIC LARYNX; GLOTTIC CARCINOMA; CANCER; RADIOTHERAPY; TIME; HEAD; NECK; CORD AB Purpose: The purpose of this paper is to present local control rates of carcinoma of the larynx in relation to the total treatment course after radical radiation therapy. Methods and Materials: A total of 1350 patients with laryngeal carcinoma treated at the Massachusetts General Hospital for the past three decades were available for analysis. Treatment courses were divided into two groups: 45 days and > 45 days. The local control rates were compared and evaluated for statistical differences. Results: The data indicated that prolonged treatment course adversely affects local tumor control of both advanced glottic and supraglottic lesions, but to a lesser degree for the early tumors. Conclusion: The study indicated that for optimal local control, radiation treatment should be completed as soon as possible, preferably within 6.5 weeks, either by once- or twice-daily accelerated programs. The local control of early T-1 glottic cancer has been exceedingly satisfactory by conventional once-daily radiation therapy. Further improvement by shortening of treatment time for such early lesions will be difficult to assess without a prospective randomized trial. RP WANG, CC (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA, USA. NR 19 TC 44 Z9 44 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1994 VL 29 IS 4 BP 657 EP 660 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NZ482 UT WOS:A1994NZ48200003 PM 8040011 ER PT J AU HALLAHAN, DE VIRUDACHALAM, S KUFE, DW WEICHSELBAUM, RR AF HALLAHAN, DE VIRUDACHALAM, S KUFE, DW WEICHSELBAUM, RR TI KETOCONAZOLE ATTENUATES RADIATION-INDUCTION OF TUMOR-NECROSIS-FACTOR SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE RADIATION SEQUELAE; TUMOR NECROSIS FACTOR; LIPOXYGENASE; KETOCONAZOLE ID FACTOR GENE-EXPRESSION; BONE-MARROW TRANSPLANTATION; IONIZING-RADIATION; PHOSPHOLIPASE-A2; ACTIVATION; CELLS; GROWTH; ACID; RNA AB Purpose: Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation induced arachidonic acid production, protein kinase C activation and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, we analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Methods and Materials: Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cyclooxygenase (indomethacin) were added to cell culture I h prior to irradiation. Results: Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenyl bromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. Conclusion: The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. We propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. C1 UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. PRITZKER SCH MED,CHICAGO,IL. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115. FU NCI NIH HHS [CA58508, CA55241, CA41068] NR 25 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1994 VL 29 IS 4 BP 777 EP 780 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NZ482 UT WOS:A1994NZ48200018 PM 8040024 ER PT J AU HUG, EB MUNZENRIDER, JE AF HUG, EB MUNZENRIDER, JE TI CHARGED-PARTICLE THERAPY FOR BASE OF SKULL TUMORS - PAST ACCOMPLISHMENTS AND FUTURE CHALLENGES SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID PROTON RP HUG, EB (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 8 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1994 VL 29 IS 4 BP 911 EP 912 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NZ482 UT WOS:A1994NZ48200037 PM 8040042 ER PT J AU WANG, CC AF WANG, CC TI TO REIRRADIATE OR NOT TO REIRRADIATE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID CARCINOMA RP WANG, CC (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 3 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 1994 VL 29 IS 4 BP 913 EP 913 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NZ482 UT WOS:A1994NZ48200038 PM 8040043 ER PT J AU DEWHIRST, FE SEYMOUR, C FRASER, GJ PASTER, BJ FOX, JG AF DEWHIRST, FE SEYMOUR, C FRASER, GJ PASTER, BJ FOX, JG TI PHYLOGENY OF HELICOBACTER ISOLATES FROM BIRD AND SWINE FECES AND DESCRIPTION OF HELICOBACTER-PAMETENSIS SP-NOV SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID CAMPYLOBACTER INFECTION; GASTRIC-CARCINOMA; PYLORI INFECTION; HOMOSEXUAL MEN; GEN-NOV; BACTERIUM; MUSTELAE; STOMACH; CINAEDI; GASTROENTERITIS AB Previously, nine fecal isolates from wild birds and a domestic swine were identified as helicobacters by phenotypic characterization and reaction with a helicobacter genus-specific DNA probe. These isolates fell into three biotypes by analysis of phenotypic traits. To further characterize these isolates, full 16S rRNA sequences were determined for strains representing each biotype, and sequence comparison indicated that the strains represented three novel, phylogenetically defined Helicobacter species. Three 16S rRNA-based DNA probes were designed and used to identify the remaining strains. Probe reactivity divided the strains into the same three groups identified phenotypically. Six of the isolates represented a new species of the genus Helicobacter for which we propose the name Helicobacter pametensis sp. nov. The following phenotypic features distinguished H. pametensis from other Helicobacter and Campylobacter species: positive tests for oxidase, catalase, alkaline phosphatase, nitrate reduction, growth at 42 degrees C, and growth in the presence of 1% glycine; negative tests for urease, gamma glutamyl transpeptidase, indoxyl acetate hydrolysis, and hippurate hydrolysis; and susceptibility to nalidixic acid and cephalothin. H. pametensis cells were motile and possessed one subterminal sheathed flagellum at each end. The two additional Helicobacter species were similar to H. pametensis except that they were urease positive, hydrolyzed indoxyl acetate, and were resistant to cephalothin. Because these two additional species are phenotypically similar and are represented by only two isolates for one species and one isolate for the other, they are not formally named but are referred to as Helicobacter sp. ''Bird-B'' and Helicobacter sp. ''Bird-C.'' These three new Helicobacter species can easily be confused with Campylobacter coil, Campylobacter lari, and Campylobacter jejuni if only a limited number of phenotypic traits are used for identification. Since it is now known that birds can harbor Helicobacter as well as Campylobacter species, methods which clearly distinguish these genera should be used to identify bird campylobacter-like isolates or bacterial strains traceable to bird fecal contamination. The zoonotic potential of these new Helicobacter species should be examined. C1 BOSTON UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02118. MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139. RP DEWHIRST, FE (reprint author), FORSYTH DENT CTR,DEPT MOLEC GENET,140 FENWAY,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-26731]; NIDCR NIH HHS [DE-10374, DE-08303] NR 47 TC 79 Z9 79 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1994 VL 44 IS 3 BP 553 EP 560 PG 8 WC Microbiology SC Microbiology GA NW043 UT WOS:A1994NW04300024 PM 7520743 ER PT J AU NIKLASON, LT CHAN, HP AF NIKLASON, LT CHAN, HP TI EVALUATION OF A PARALLEL HOLE GRID FOR BEDSIDE CHEST IMAGING SO INVESTIGATIVE RADIOLOGY LA English DT Article DE RADIOGRAPHY, BEDSIDE; THORAX, RADIOGRAPHY; RADIOGRAPHY, TECHNOLOGY ID RADIOGRAPHY AB RATIONALE AND OBJECTIVES. The application of a new parallel hole grid designed for bedside radiography is investigated. This grid is constructed of sheets of holes and is designed to have more tolerance to positioning errors than conventional grids. METHODS. The parallel hole grid is compared to conventional 6:1 and 12:1 grids using phantoms. The contrast improvement, scatter fractions, exposure, and tolerance to positioning errors are measured. RESULTS. The parallel hole grid has much more tolerance to positioning errors than conventional grids. The contrast improvement and scatter rejection are significantly less than those obtained with a conventional 6:1 ratio grid. Compared with nongrid techniques, the parallel hole grid provides 13% to 20% higher lung contrast. CONCLUSIONS. The parallel hole grid may be used for beside imaging without the need for accurate alignment. The parallel hole grid requires approximately 2.7 times the entrance expo sure of a nongrid technique. Lung contrast improvement is approximately half of that from an accurately aligned 6:1 conventional grid. For grid angulation greater than 8 degrees, the parallel hole grid provides higher contrast than the 6:1 grid. C1 UNIV MICHIGAN HOSP,DEPT RADIOL,ANN ARBOR,MI 48109. RP NIKLASON, LT (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL SCI & TECHNOL,BOSTON,MA 02114, USA. NR 8 TC 2 Z9 2 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 JUL PY 1994 VL 29 IS 7 BP 682 EP 688 DI 10.1097/00004424-199407000-00004 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PC301 UT WOS:A1994PC30100004 PM 7960614 ER PT J AU REESE, TG PEARLMAN, JD AF REESE, TG PEARLMAN, JD TI MR GRADIENT RESPONSE MODELING TO ENSURE EXCITATION COHERENCE SO JMRI-JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE ARTIFACT; GRADIENT WAVE-FORMS; IMAGE PROCESSING; K-SPACE; MATHEMATICAL MODEL; PULSE SEQUENCES ID EDDY-CURRENT COMPENSATION; NMR; DIMENSIONS; COILS AB Gradient system response has a significant effect on the shape and dispersion of complex k-space trajectories, as used in echo-planar magnetic resonance imaging and designed excitation. The authors have developed a method that characterizes the gradient response directly by placing k-space ''landmarks'' in the raw data. The method produces a clear delineation of the k-space trajectory. while providing information about related factors such as magnetic field homogeneity and temporal coherence of the radio-frequency (RF) and gradient waveforms. By using parameters derived from data collected under varying conditions, gradient response is modeled as a linear system consisting of a response delay function with a frequency-dependent slope. The results allow corrections that can be applied to the RF waveform or to the k-space trajectory. Application of this correction to designed excitation with the sinusoidal k-space trajectory is demonstrated and discussed. C1 BETH ISRAEL HOSP,DEPT RADIOL,330 BROOKLINE AVE,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,CTR NMR IMAGING,BOSTON,MA 02114. NR 17 TC 11 Z9 11 U1 0 U2 1 PU SOC MAGNETIC RESONANCE IMAGING PI EASTON PA 1991 NORTHAMPTON ST, EASTON, PA 18042-3189 SN 1053-1807 J9 JMRI-J MAGN RESON IM JI JMRI-J. Magn. Reson. Imaging PD JUL-AUG PY 1994 VL 4 IS 4 BP 569 EP 576 DI 10.1002/jmri.1880040410 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NY660 UT WOS:A1994NY66000009 PM 7949683 ER PT J AU ALPERT, JE MADDOCKS, A ROSENBAUM, JF FAVA, M AF ALPERT, JE MADDOCKS, A ROSENBAUM, JF FAVA, M TI CHILDHOOD PSYCHOPATHOLOGY RETROSPECTIVELY ASSESSED AMONG ADULTS WITH EARLY-ONSET MAJOR DEPRESSION SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE DEPRESSION; COMORBIDITY; CHILDHOOD; ADOLESCENT; PSYCHOPATHOLOGY; ANXIETY ID ANXIETY DISORDERS; CO-MORBIDITY; CHILDREN; COMORBIDITY; ADOLESCENTS; CONDUCT; PARENTS; RISK; RECOVERY; AGE AB Prevalence and impact of comorbidity in early onset major depressive disorder were studied in 116 depressed adult outpatients whose onset of first major depressive episode occurred by age 18. Eighty-eight percent of these patients had at least one additional comorbid Axis I lifetime diagnosis including: social phobia (28%), simple phobia (16%), alcohol (17%) and cannabis (13%) abuse/dependence, and bulimia nervosa (8%). Comorbid anxiety disorders preceded the onset of major depression in two-thirds of individuals while comorbid substance abuse/dependence followed the onset of major depression in two-thirds and predicted more frequent occurrences into adulthood. In contrast to frequency of episodes, severity and duration of an index episode of major depression were not influenced by comorbidity. RP ALPERT, JE (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL UNIT,DEPRESS RES PROGRAM,ACC 815,BOSTON,MA 02114, USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [NIMH R1MH48483-01] NR 24 TC 43 Z9 45 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JUL PY 1994 VL 31 IS 3 BP 165 EP 171 DI 10.1016/0165-0327(94)90025-6 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NX891 UT WOS:A1994NX89100002 PM 7963068 ER PT J AU TURNIDGE, JD GUDMUNDSSON, S VOGELMAN, B CRAIG, WA AF TURNIDGE, JD GUDMUNDSSON, S VOGELMAN, B CRAIG, WA TI THE POSTANTIBIOTIC EFFECT OF ANTIFUNGAL AGENTS AGAINST COMMON PATHOGENIC YEASTS SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID CANDIDA-ALBICANS; 5-FLUOROCYTOSINE; INFECTIONS; NETILMICIN C1 DEPT MED LANDSPITALINN,IS-101 REYKJAVIK,ICELAND. MONASH MED CTR,DEPT INFECT DIS & MICROBIOL,CLAYTON,VIC 3168,AUSTRALIA. UNIV ICELAND,SCH MED,IS-101 REYKJAVIK,ICELAND. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MED SERV,MADISON,WI 53705. UNIV WISCONSIN,DEPT MED,MADISON,WI 53705. NR 24 TC 68 Z9 70 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUL PY 1994 VL 34 IS 1 BP 83 EP 92 DI 10.1093/jac/34.1.83 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA NY308 UT WOS:A1994NY30800008 PM 7961219 ER PT J AU ANZUETO, A BRASSARD, JM ANDRADE, FH LAWRENCE, RA MAXWELL, LC LEVINE, SM JENKINSON, SG AF ANZUETO, A BRASSARD, JM ANDRADE, FH LAWRENCE, RA MAXWELL, LC LEVINE, SM JENKINSON, SG TI EFFECTS OF HYPEROXIA ON RAT DIAPHRAGM FUNCTION SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE FATIGUE; RESPIRATORY MUSCLES; FREE RADICALS; RESISTIVE BREATHING; GLUTATHIONE; CONTRACTILE PROPERTIES ID OXYGEN-TOXICITY; SKELETAL-MUSCLE; REACTIVE OXYGEN; BLOOD-FLOW; FATIGUE; GLUTATHIONE; LUNG; PERFORMANCE; 100-PERCENT AB The association of oxygen radical generation with impaired diaphragm performance has previously been reported after inspiratory resistive loading (IRL). We hypothesized that exposure of rats to normobaric hyperoxia (O-2) could produce impaired diaphragm function because of free radical production. Sprague-Dawley rats were divided into four groups: 1) room air (control), 2) > 95% O-2 for 24 h, 3) > 95% O-2 for 48 h, and 4) > 95% O-2 for 60 h. Each group was studied at rest after the O-2 exposure and then after IRL. During IRL, the animals breathed through an inspiratory resistor until they were unable to sustain > 70% of the maximum airway pressure. Diaphragm samples were obtained for analysis of glutathione (GSH) and glutathione disulfide (GSSG) concentrations. In vitro isometric contractile properties were also determined, including maximal tetanic tension (P-o) and maximal twitch tension (P-t), in GSSG content and in GSSG-to-GSH ratios. Hyperoxia for > 48 h resulted in significant decreases in P-o and P-t and an increase in GSSG content and in GSSG-to-GSH ratios compared with other groups. Those same animals subjected to IRL showed a further decrease in P-o and P-t. These data suggest that free radical generation may occur in the diaphragm during a hyperoxia exposure associated with activation of the GSH redox cycle and impairment of diaphragm function. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV PULM DIS CRIT CARE,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,DIV PULM DIS CRIT CARE,SAN ANTONIO,TX 78284. BROOKE ARMY MED CTR,SAN ANTONIO,TX 78284. RP ANZUETO, A (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,DIV PULM DIS CRIT CARE 111E,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. RI Andrade, Francisco/F-1258-2011 OI Andrade, Francisco/0000-0002-2460-5798 FU NHLBI NIH HHS [HL-32824] NR 31 TC 8 Z9 8 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 JUL PY 1994 VL 77 IS 1 BP 63 EP 68 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA NX536 UT WOS:A1994NX53600011 PM 7961276 ER PT J AU MCKEE, M JUPITER, J TOH, CL WILSON, L COLTON, C KARRAS, KK AF MCKEE, M JUPITER, J TOH, CL WILSON, L COLTON, C KARRAS, KK TI RECONSTRUCTION AFTER MALUNION AND NONUNION OF INTRAARTICULAR FRACTURES OF THE DISTAL HUMERUS - METHODS AND RESULTS IN 13 ADULTS SO JOURNAL OF BONE AND JOINT SURGERY-BRITISH VOLUME LA English DT Article ID ELBOW AB We reviewed the results in 13 adults of secondary reconstruction of malunited and ununited intra-articular distal humeral fractures. Their average age was 39.7 years, and preoperatively all had pain, loss of motion and functional disability; the average are of motion was only 43 degrees and the average flexion contracture was 45 degrees. Nine patients had ulnar neuropathy. Elbow reconstruction, at an average of 13.4 months after the original injury, included osteotomy for malunion or debridement for nonunion, realignment with stable fixation and autogenous bone grafts, anterior and posterior capsulectomy and ulnar neurolysis. The elbows were mobilised 24 hours postoperatively. There were no early complications and all nonunions and intra-articular osteotomies healed. After a mean follow-up of 25 months, the average arc of motion was 97 degrees with no progressive radiographic degeneration. Ulnar nerve function improved in all cases and clinical assessment using the Morrey score showed two excellent, eight good and three fair results. Reconstruction of intra-articular malunion and nonunion of the distal humerus in young active adults is technically challenging, but can improve function by restoring the intrinsic anatomy of the elbow. C1 MASSACHUSETTS GEN HOSP, ORTHOPAED TRAUMA SERV, BOSTON, MA 02114 USA. UNIV NOTTINGHAM HOSP, QUEENS MED CTR, DEPT ORTHOPAED TRAUMA, NOTTINGHAM NG7 2UH, ENGLAND. RP MCKEE, M (reprint author), ST MICHAELS HOSP, SUITE 800, 55 QUEEN ST E, TORONTO M5C 1R6, ON, CANADA. NR 19 TC 60 Z9 62 U1 0 U2 0 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 0301-620X EI 2044-5377 J9 J BONE JOINT SURG BR JI J. Bone Joint Surg.-Br. Vol. PD JUL PY 1994 VL 76B IS 4 BP 614 EP 621 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA NY315 UT WOS:A1994NY31500025 PM 8027152 ER PT J AU LO, EH MATSUMOTO, K PIERCE, AR GARRIDO, L LUTTINGER, D AF LO, EH MATSUMOTO, K PIERCE, AR GARRIDO, L LUTTINGER, D TI PHARMACOLOGICAL REVERSAL OF ACUTE CHANGES IN DIFFUSION-WEIGHTED MAGNETIC-RESONANCE-IMAGING IN FOCAL CEREBRAL-ISCHEMIA SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE STROKE; DIFFUSION-WEIGHTED MRI; NEUROPROTECTION; PHARMACOTHERAPY; GLUTAMATE; RAT ID GLUTAMATE ANTAGONIST MK-801; NEURONAL INJURY; BLOOD-FLOW; TEMPORAL EVOLUTION; RAT; DAMAGE; NMDA; STROKE; MECHANISMS; CULTURE AB Recently, diffusion-weighted magnetic resonance imaging (DWI) has been shown to visualize acute ischemic lesions in the brain before changes are observable with conventional magnetic resonance imaging. However, the underlying mechanisms of these acute DWI changes are unclear and may include both reversible and irreversible damage. In this study, we demonstrate that acute DWI lesions may be reversed with MK801 therapy postischemia. Sprague-Dawley rats (n = 12) were subjected to middle cerebral artery occlusion and DWI scans were obtained beginning 600 min postocclusion. Distinct regions of hyperintensity were observed in the basal ganglia and cortex, corresponding with the expected distribution of ischemia in this model. After the first scan, animals were treated with MK801 (0.5 mg/kg i.v.) or normal saline and subsequently scanned again 30 and 60 min after treatment. In the control group, the area of hyperintense lesions continued to increase, by 55% in the cortex and 57% in the basal ganglia. MK801 therapy significantly (p < 0.01) reduced the area of damage by the third DWI scan at 60 min posttreatment (-50% cortex, -22% basal ganglia, -41% total hemisphere) compared to pretreatment scans. Tetrazolium (TTC) stains at 24 h confirmed that MK801 significantly reduced the volumes of infarction (p < 0.05). These results demonstrate that significant portions of the acute ischemic lesion on DWI are reversible with pharmacologic intervention. . C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,MGH NMR CTR,BOSTON,MA 02114. STERLING WINTHROP INC,DIV PHARMACEUT RES,NEUROSCI GRP,COLLEGEVILLE,PA. NEW YORK STATE DEPT HLTH,BUR TOX SUBST ASSESSMENT,NEW YORK,NY. RI Garrido, Leoncio/K-3092-2014 OI Garrido, Leoncio/0000-0002-7587-1260 NR 28 TC 70 Z9 70 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 1994 VL 14 IS 4 BP 597 EP 603 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA NT499 UT WOS:A1994NT49900008 PM 8014206 ER PT J AU KOSOFSKY, BE WILKINS, AS GRESSENS, P EVRARD, P AF KOSOFSKY, BE WILKINS, AS GRESSENS, P EVRARD, P TI TRANSPLACENTAL COCAINE EXPOSURE - A MOUSE MODEL DEMONSTRATING NEUROANATOMICAL AND BEHAVIORAL ABNORMALITIES SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID PRENATAL COCAINE; VISUAL-CORTEX; RAT-BRAIN; PREGNANCY; UNDERNUTRITION; FETAL; MALNUTRITION; GESTATION; TOXICITY; DRUGS AB Between 10% and 15% of infants born in urban America today have been exposed to cocaine in utero. clinical studies have suggested that impairment of brain growth is the single best marker of significant prenatal cocaine exposure, and postnatal developmental compromised seen in a subset of affected children as a consequence of that exposure. We have developed an animal model, in mice, of prenatal cocaine exposure that has allowed us to dissociate the direct effects of cocaine in altering fetal development from the indirect effects associated with cocaine-induced malnutrition. We find that transplacental cocaine exposure independently impairs fetal brain and body growth and results in behavioural deficits and permanent alterations in neocortical cytoarchitecture in exposed offspring. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV CATHOLIQUE LOUVAIN,SCH MED,NEUROL DEV LAB,B-1200 BRUSSELS,BELGIUM. RP KOSOFSKY, BE (reprint author), MASSACHUSETTS GEN HOSP E,MOLEC & DEV NEUROSCI LAB,CNY-2W,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NIDA NIH HHS [DA00175] NR 34 TC 61 Z9 61 U1 1 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD JUL PY 1994 VL 9 IS 3 BP 234 EP 241 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA PG168 UT WOS:A1994PG16800003 PM 7930401 ER PT J AU LAMBERTMESSERLIAN, GM HALL, JE SLUSS, PM TAYLOR, AE MARTIN, KA GROOME, NP CROWLEY, WF SCHNEYER, AL AF LAMBERTMESSERLIAN, GM HALL, JE SLUSS, PM TAYLOR, AE MARTIN, KA GROOME, NP CROWLEY, WF SCHNEYER, AL TI RELATIVELY LOW-LEVELS OF DIMERIC INHIBIN CIRCULATE IN MEN AND WOMEN WITH POLYCYSTIC-OVARIAN-SYNDROME USING A SPECIFIC 2-SITE ENZYME-LINKED-IMMUNOSORBENT-ASSAY SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; SERUM INHIBIN; IMMUNOREACTIVE INHIBIN; LUTEINIZING-HORMONE; GENE-EXPRESSION; HUMAN-PLACENTA; ALPHA-SUBUNIT; CORPUS-LUTEUM; SECRETION; PLASMA AB The endocrine feedback role of dimeric inhibin on FSH secretion from the pituitary has been well established in many species; however, evidence that inhibin is an important endocrine regulator of FSH in the human is more tenuous. One potential explanation for the equivocal data may be that the inhibin immunoassay used most widely in the human is a heterologous assay with an antiserum that exclusively recognizes the inhibin alpha-subunit in both its monomeric form and in inhibin dimers. The aim of the present study was to quantify serum inhibin levels in a variety of fertile and infertile men and women using a new ultrasensitive enzyme-linked immunosorbent assay that is specific for the dimeric form ((alpha/beta) only. The specificity of the present assay was demonstrated by the absence of significant cross-reactivity with Mullerian inhibiting substance, transforming growth factor-beta, activin, FSH, LH, hCG, TSH, and hCG alpha and with the alpha-subunit of inhibin. The assay was sensitive to 1 pg/mL, and serial dilutions of human male and female serum samples paralleled the recombinant 32-kilodalton (kDa) dimeric inhibin standard curve. Complete recovery of exogenous recombinant 32-kDa inhibin added to serum was obtained. Mean serum inhibin levels ranged from a low of 5.7 +/- 0.6 pg/mL in the early follicular phase to 49.0 c 11.2 pg/mL in the midluteal phase of the normal menstrual cycle and were elevated during ovulation induction (1250 pg/mL) and pregnancy (500 pg/mL). interestingly, mean levels of dimeric inhibin in women with polycystic ovarian syndrome (PCOS) were indistinguishable from normal follicular phase. The most striking observation was the extremely low mean inhibin levels (<2 pg/mL) found in normal men, GnRH-deficient men before any pulsatile GnRH treatment, and men with Klinefelter's syndrome, all of which were indistinguishable from levels observed in postmenopausal women. These observations in the male raise the possibly that 1) some forms of circulating and bioactive inhibin in the human are not detected by this assay due to either their conformation or the presence of a unique binding protein for endogenous inhibin that does not bind to recombinant 32-kDa inhibin; or 2) dimeric inhibin is not a major endocrine regulator of FSH in the human male. In addition, the relatively high dimeric inhibin levels at midcycle and in the luteal phase of the normal menstrual cycle, after gonadotropin stimulation, and during pregnancy suggest that dimeric inhibin is predominantly produced by dominant follicles, corpora lutea, and placental tissues. C1 OXFORD BROOKES UNIV, SCH BIOL & MOLEC SCI, OXFORD OX3 0BP, ENGLAND. RP LAMBERTMESSERLIAN, GM (reprint author), MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, REPROD ENDOCRINE UNIT, BHX-5, 32 FRUIT ST, BOSTON, MA 02114 USA. OI Messerlian, Geralyn/0000-0002-9440-3411 FU NICHD NIH HHS [T32-HD-07396, R01 HD015788, R01-HD-15788, T32 HD007396, U54-HD-29164] NR 50 TC 92 Z9 94 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1994 VL 79 IS 1 BP 45 EP 50 DI 10.1210/jc.79.1.45 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NW509 UT WOS:A1994NW50900011 PM 8027251 ER PT J AU LEON, SP CARROLL, RS DASHNER, K GLOWACKA, D BLACK, PM AF LEON, SP CARROLL, RS DASHNER, K GLOWACKA, D BLACK, PM TI MESSENGER-RIBONUCLEIC-ACID EXPRESSION OF PLATELET-DERIVED GROWTH-FACTOR SUBUNITS AND RECEPTORS IN PITUITARY-ADENOMAS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CLONAL ORIGIN; FACTOR PDGF; CELL-LINES; FACTOR-I; CARCINOMAS; BIOLOGY; CANCER; INVIVO; TISSUE; GENES AB Little is known about the expression of growth factors and their receptors in pituitary tumors or the relationship of growth factors to pituitary neoplasia. Platelet-derived growth factor (PDGF) is a potent mitogen that has been postulated to stimulate tumor growth through autocrine and/or paracrine loops in a number of human tumors. In the present study we demonstrate messenger ribonucleic acid expression of the PDGF subunits and receptors in a variety of human pituitary adenomas and in a normal human anterior pituitary gland. Northern blot analysis performed on 34 pituitary adenomas showed that all tumors expressed the PDGF-A and PDGF-B subunits, the majority (94%) expressed the PDGF-beta receptor, and a subset (44%) expressed the PDGF-alpha receptor. The normal anterior pituitary studied expressed all of the PDGF subunits and receptor subunits. Clinically, there was no correlation between expression of the PDGF subunits or receptors and tumor size or with invasion into adjacent structures (cavernous sinus, sphenoid sinus, or clivus). A higher proportion of the endocrinologically active adenomas expressed the PDGF-alpha receptor (5 of 8) compared to the endocrine inactive tumors (10 of 26). The function of PDGF in the pituitary is currently not known. The finding that PDGF subunit and receptor messenger ribonucleic acids are coexpressed in pituitary adenomas and normal anterior pituitary suggests that autocrine and/or paracrine loops involving PDGF may exist in pituitary adenomas and normal anterior pituitary. C1 BRIGHAM & WOMENS HOSP, CHILDRENS HOSP, DANA FARBER CANC INST, NEUROSURG LABS, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, CHILDRENS HOSP, DANA FARBER CANC INST, CTR BRAIN TUMOR, BOSTON, MA 02115 USA. NR 31 TC 12 Z9 12 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1994 VL 79 IS 1 BP 51 EP 55 DI 10.1210/jc.79.1.51 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NW509 UT WOS:A1994NW50900012 PM 8027252 ER PT J AU TAYLOR, AE KHOURY, RH CROWLEY, WF AF TAYLOR, AE KHOURY, RH CROWLEY, WF TI A COMPARISON OF 13 DIFFERENT IMMUNOMETRIC ASSAY KITS FOR GONADOTROPINS - IMPLICATIONS FOR CLINICAL INVESTIGATION SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLYCOPROTEIN HORMONES; ALPHA-SUBUNIT; PITUITARY; WOMEN; SECRETION; ADENOMAS; CYCLE; AXIS; MEN AB To determine whether the new immunometric (sandwich) assays for gonadotropins achieve the alleged improvements over RIAs, we compared 13 commercial kits for LH and FSH with our established and validated polyclonal RIAs. Although the kits claimed detection limits as low as 0.05 IU/L, when sensitivity was tested with a uniform hormone standard (the Second International Reference Preparation of human menopausal gonadotropin urinary standard) and the requirement that the limit must be determined from a detectable standard point rather than the variance around zero, only 4 kits surpassed the detectability achieved by the existing LH and FSH RIAs. Seven of the 10 LH kits tested displayed greater than 10% cross-reactivity with either the alpha- or LH beta-subunit. The relationship between the kit standard and the Second International Reference Preparation of human menopausal gonadotropin uniform standard in each kit was nonlinear, so that attempts to compare results between assays with simple multiplication factors are inaccurate. Only 2 assays were designed to eliminate a hook effect. The following conclusions were reached. 1) Most available gonadotropin immunometric assays do not yet offer features not already available in existing validated polyclonal research assays. 2) Conversion of data from one assay to another is not straightforward. 3) Many of the manufacturers' claims do not appear justified. 4) Determination of the detection limit and other immunometric assay characteristics requires standardization of criteria. We propose the following minimum criteria for validating gonadotropin immunometric assays: 1) a uniform definition of the detection limit based on the lowest distinguishable standard concentration, 2) determination of the standard concentration at which a hook occurs, 3) determination of cross-reactivity to subunits as well as intact gonadotropins, and 4) establishment of an adequate normative data base. C1 MASSACHUSETTS GEN HOSP, DEPT MED, REPROD ENDOCRINE UNIT, BOSTON, MA 02114 USA. RP TAYLOR, AE (reprint author), MASSACHUSETTS GEN HOSP, NATL CTR INFERTIL RES, BARTLETT HALL EXTENS 511, FRUIT ST, BOSTON, MA 02114 USA. FU NICHD NIH HHS [U54-HD-29164, R01-HD-15080]; NIDDK NIH HHS [T32-DK-07028] NR 19 TC 53 Z9 54 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1994 VL 79 IS 1 BP 240 EP 247 DI 10.1210/jc.79.1.240 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NW509 UT WOS:A1994NW50900044 PM 8027235 ER PT J AU TATERKA, J SUTCLIFFE, M RUBIN, DH AF TATERKA, J SUTCLIFFE, M RUBIN, DH TI SELECTIVE REOVIRUS INFECTION OF MURINE HEPATOCARCINOMA CELLS DURING CELL-DIVISION - A MODEL OF VIRAL LIVER INFECTION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE RECEPTORS; VIRUS; LIVER REGENERATION; CELL CYCLE; INTESTINAL INFECTION; CELLULAR DIFFERENTIATION ID ADULT HUMAN HEPATOCYTES; HEPATITIS-B VIRUS; GROWTH-FACTOR; ALCOHOLIC PATIENTS; DISEASE; BINDING; TYPE-3; CYCLE; MICE; TRANSCRIPTION AB Reovirus type 1, strain Lang (1/L), can infect hepatocytes in vivo only after hepatocellular damage is induced by hepatotoxins, surgical trauma, resection, or profound immunosuppression. To examine the role of cell cycle and cellular differentiation on liver cell susceptibility to reovirus infection, a murine hepatocarcinoma cell line, Hepa 1/A1, was infected with reovirus and assayed for the presence of infectious virus or reovirus antigen in cells. Despite a > 95% binding of reovirus to hepatocarcinoma cells as indicated by cytometric analysis; only 10% of hepatoma cells contained infectious virus by infectious center assay. In comparison, 100% of L cells were infected. Analysis of intracellular reovirus antigen revealed its presence in dividing but not in quiescent hepatocytes. This correlation of cellular division and cell capacity to support viral replication suggests that induction of hepatocyte proliferation may be a mechanism for liver susceptibility to reovirus infection. C1 VET AFFAIRS MED CTR,DEPT MED RES,ACOS RES,NASHVILLE,TN 37212. UNIV PENN,DEPT BIOL,PHILADELPHIA,PA 19104. UNIV PENN,DIV GASTROENTEROL MED,PHILADELPHIA,PA 19104. DEPT VET AFFAIRS MED CTR,DEPT MED RES,PHILADELPHIA,PA 19104. VANDERBILT UNIV,MED CTR,DEPT MED,DIV INFECT DIS,NASHVILLE,TN 37212. VANDERBILT UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,NASHVILLE,TN 37212. FU NIAID NIH HHS [AI-23970]; NIDDK NIH HHS [T-32-DK-07066] NR 40 TC 14 Z9 14 U1 0 U2 1 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 JUL PY 1994 VL 94 IS 1 BP 353 EP 360 DI 10.1172/JCI117329 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NW496 UT WOS:A1994NW49600045 PM 8040276 ER PT J AU DIGNASS, A LYNCHDEVANEY, K KINDON, H THIM, L PODOLSKY, DK AF DIGNASS, A LYNCHDEVANEY, K KINDON, H THIM, L PODOLSKY, DK TI TREFOIL PEPTIDES PROMOTE EPITHELIAL MIGRATION THROUGH A TRANSFORMING GROWTH-FACTOR BETA-INDEPENDENT PATHWAY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE MUCOSAL INJURY; GROWTH; GOBLET CELLS; HEALING ID PANCREATIC SPASMOLYTIC POLYPEPTIDE; INFLAMMATORY BOWEL-DISEASE; XENOPUS-LAEVIS SKIN; HUMAN COLONIC MUCIN; P-DOMAIN; INTEGUMENTARY MUCIN; MUCOSAL ULCERATION; STOMACH MUCOSA; INVITRO MODEL; CELL-LINE AB The trefoil peptides, a recently recognized family of protease-resistant peptides, expressed in a regional specific pattern throughout the normal gastrointestinal tract. Although these peptides have been hypothesized to act as growth factors, their functional properties are largely unknown. Addition of recombinant trefoil peptides human spasmolytic polypeptide (HSP), rat and human intestinal trefoil factor (RITF and HITF) to subconfluent nontransformed rat intestinal epithelial cell Lines (IEC-6 and IEC-17), human colon cancer-derived cell lines (HT-29 and CaCO2) or nontransformed fibroblasts (NRK and BHK) had no significant effect on proliferation. However addition of the trefoil peptides to wounded monolayers of confluent IEC-6 cells in an in vitro model of epithelial restitution resulted in a 3-6-fold increase in the rate of epithelial migration into the wound. Stimulation of restitution by the trefoil peptide HSP was enhanced in a cooperative fashion by the addition of mucin glycoproteins purified from the colon or small intestine of either rat or man, achieving up to a 15-fold enhancement in restitution. No synergistic effect was observed by the addition of nonmucin glycoproteins. In contrast to cytokine stimulation of intestinal epithelial cell restitution which is mediated through enhanced TGF beta bioactivity, trefoil peptide, and trefoil peptide-mucin glycoprotein stimulation of restitution was not associated with alteration in concentrations of bioactive TGF-beta and was not affected by the presence of immunoneutralizing anti-TGF beta antiserum. Collectively, these findings suggest that the trefoil peptides which are secreted onto the lumenal surface of the gastrointestinal tract may act in conjunction with the mucin glycoprotein products of goblet cells to promote reestablishment of mucosal integrity after injury through mechanisms distinct from those which may act at the basolateral pole of the epithelium. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NERPRC,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02114. NOVO RES INST,DK-2880 COPENHAGEN,DENMARK. FU NIDDK NIH HHS [DK-34422, DK-43351] NR 50 TC 381 Z9 401 U1 1 U2 14 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 JUL PY 1994 VL 94 IS 1 BP 376 EP 383 DI 10.1172/JCI117332 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NW496 UT WOS:A1994NW49600048 PM 8040278 ER PT J AU PFALLER, MA BALE, M BUSCHELMAN, B LANCASTER, M ESPINELINGROFF, A REX, JH RINALDI, MG AF PFALLER, MA BALE, M BUSCHELMAN, B LANCASTER, M ESPINELINGROFF, A REX, JH RINALDI, MG TI SELECTION OF CANDIDATE QUALITY-CONTROL ISOLATES AND TENTATIVE QUALITY-CONTROL RANGES FOR IN-VITRO SUSCEPTIBILITY TESTING OF YEAST ISOLATES BY NATIONAL COMMITTEE FOR CLINICAL LABORATORY STANDARDS PROPOSED STANDARD METHODS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; FUNGAL-INFECTIONS; FLUCONAZOLE RESISTANCE; BROTH MACRODILUTION; EPIDEMIOLOGY; PATHOGENS AB The National Committee for Clinical Laboratory Standards has developed a proposed standard method for in vitro antifungal susceptibility testing of yeast isolates (National Committee for Clinical Laboratory Standards, document M27-P, 1992). In order for antifungal testing by the M27-P method to be accepted, reliable quality control (QC) performance criteria must be developed. In the present study, five laboratories tested 10 candidate QC strains 20 times each against three antifungal agents: amphotericin B, fluconazole, and 5-fluorocytosine. All sites conformed to the M27-P standards and used a common lot of tube dilution reagents and RPMI 1640 broth medium. Overall, 98% of MIC results with amphotericin B, 95% with fluconazole, and 92% with 5-fluorocytosine fell within the desired 3-log(2) dilution range (mode +/- 1 log(2) dilution). Excellent performance with all three antifungal agents was observed for six strains: Candida albicans ATCC 90028, Candida parapsilosis ATCC 90018, C. parapsilosis ATCC 22019, Candida krusei ATCC 6258, Candida tropicalis ATCC 750, and Saccharomyces cerevisiae ATCC 9763. With these strains, 3-log, dilution ranges encompassing 94 to 100% of MICs for all three drugs were established. Additional studies with multiple lots of RPMI 1640 test medium will be required to establish definitive QC ranges. C1 ALAMAR BIOSCI INC,SACRAMENTO,CA 95834. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. UNIV TEXAS,SCH MED,HOUSTON,TX 77030. UNIV TEXAS,AUDIE L MURPHY MEM VET ADM MED CTR,CTR HLTH SCI,LAB SERV,SAN ANTONIO,TX 78284. RP PFALLER, MA (reprint author), UNIV IOWA,COLL MED,MRC 273,DEPT PATHOL,IOWA CITY,IA 52242, USA. NR 34 TC 50 Z9 51 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 JUL PY 1994 VL 32 IS 7 BP 1650 EP 1653 PG 4 WC Microbiology SC Microbiology GA NR924 UT WOS:A1994NR92400006 PM 7929752 ER PT J AU SWENSON, JM CLARK, NC FERRARO, MJ SAHM, DF DOERN, G PFALLER, MA RELLER, LB WEINSTEIN, MP ZABRANSKY, RJ TENOVER, FC AF SWENSON, JM CLARK, NC FERRARO, MJ SAHM, DF DOERN, G PFALLER, MA RELLER, LB WEINSTEIN, MP ZABRANSKY, RJ TENOVER, FC TI DEVELOPMENT OF A STANDARDIZED SCREENING METHOD FOR DETECTION OF VANCOMYCIN-RESISTANT ENTEROCOCCI SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article AB The incidence of vancomycin resistance among enterococci is increasing in the United States and elsewhere in the world, but automated susceptibility testing methods have difficulty detecting resistance expressed by certain strains. The agar screening method described by Willey et al. (B. M. Willey, B. N. Kreiswirth, A. E. Simor, G. Williams, S. R. Scriver, A. Phillips, and D. E. Low, J. Clin. Microbiol. 30:1621-1624, 1992) has been proposed as a reliable method for confirming vancomycin resistance. In this study, we investigated various parameters associated with the agar screening method and, on the basis of the findings, established optimum testing conditions for the method. First, to evaluate media and vancomycin concentrations, one laboratory used Mueller-Hinton and brain heart infusion agars supplemented with 4, 6, and 8 mu g of vancomycin per ml to test 100 genetically characterized enterococcal strains. On the basis of the results obtained, brain heart infusion agar supplemented with 6 mu g of vancomycin per ml was selected for further study. Subsequently, eight laboratories used the medium to test both reference and clinical isolates. There was very good performance with the reference strains and, among 158 clinical isolates tested, the method demonstrated sensitivity and specificity of 100% and from 96 to 99%, respectively. C1 MASSACHUSETTS GEN HOSP,MICROBIOL LAB,BOSTON,MA 02114. JEWISH HOSP ST LOUIS,MICROBIOL LAB,ST LOUIS,MO 63110. UNIV MASSACHUSETTS,MED CTR,DEPT CLIN MICROBIOL,WORCESTER,MA 01655. OREGON HLTH SCI UNIV,DEPT PATHOL,PORTLAND,OR 97201. DUKE UNIV,MED CTR,CLIN MICROBIOL LAB,DURHAM,NC 27710. UNIV MED & DENT NEW JERSEY HOSP,ROBERT WOOD JOHNSON MED SCH,MICROBIOL LAB,NEW BRUNSWICK,NJ 08903. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. RP SWENSON, JM (reprint author), CTR DIS CONTROL,HOSP INFECT PROGRAM,1600 CLIFTON RD,MAILSTOP G08,1-3361,ATLANTA,GA 30333, USA. NR 17 TC 70 Z9 78 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1994 VL 32 IS 7 BP 1700 EP 1704 PG 5 WC Microbiology SC Microbiology GA NR924 UT WOS:A1994NR92400015 PM 7929760 ER PT J AU VOGELZANG, NJ WEISSMAN, LB HERNDON, JE ANTMAN, KH COOPER, MR CORSON, JM GREEN, MR AF VOGELZANG, NJ WEISSMAN, LB HERNDON, JE ANTMAN, KH COOPER, MR CORSON, JM GREEN, MR TI TRIMETREXATE IN MALIGNANT MESOTHELIOMA - A CANCER AND LEUKEMIA GROUP-B PHASE-II STUDY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-TRIALS; METHOTREXATE; EXPERIENCE; PATTERNS; DIFFUSE; DISEASE; PLEURA C1 MT AUBURN HOSP,DEPT MED,CAMBRIDGE,MA. DANA FARBER CANC INST,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV SURG PATHOL,BOSTON,MA 02115. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. CANC & LEUKEMIA GRP B,CTR STAT,DURHAM,NC. RP VOGELZANG, NJ (reprint author), UNIV CHICAGO,MED CTR,DEPT MED,HEMATOL ONCOL SECT,5841 S MARYLAND AVE,MC 2115,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA41287, CA33601, CA32991] NR 31 TC 58 Z9 58 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 JUL PY 1994 VL 12 IS 7 BP 1436 EP 1442 PG 7 WC Oncology SC Oncology GA NW075 UT WOS:A1994NW07500015 PM 8021735 ER PT J AU PATTERSON, WB EMANUEL, EJ AF PATTERSON, WB EMANUEL, EJ TI EUTHANASIA AND THE CARE OF CANCER-PATIENTS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Discussion ID LIFE RP EMANUEL, EJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 6 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL PY 1994 VL 12 IS 7 BP 1516 EP 1521 PG 6 WC Oncology SC Oncology GA NW075 UT WOS:A1994NW07500024 PM 7517444 ER PT J AU COHEN, LS SICHEL, DA DIMMOCK, JA ROSENBAUM, JF AF COHEN, LS SICHEL, DA DIMMOCK, JA ROSENBAUM, JF TI IMPACT OF PREGNANCY ON PANIC DISORDER - A CASE SERIES SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 146th Annual Meeting of the American-Psychiatric-Association CY MAY 27, 1993 CL SAN FRANCISCO, CA SP AMER PSYCHIAT ASSOC ID ATTACKS; CHILDBEARING; AGORAPHOBIA; DEPRESSION; WOMEN AB Background: Pregnancy has a variable impact on the course of panic disorder. Some patients describe diminished anxiety symptoms during pregnancy, while others note persistence or worsening of symptoms. Method: We retrospectively evaluated the clinical course of 49 women with pregravid panic disorder across three trimesters of pregnancy and evaluated the extent to which severity of pregravid panic disorder predicted course of anxiety symptoms, medication received, and ability to discontinue medication during pregnancy. Results: While 38 women (78%) were noted either to have insignificant change in status or to have clinical improvement, 10 women (20%) evinced more severe panic symptoms during pregnancy. More severely ill women received pharmacotherapeutic intervention during some portion of their pregnancy compared with less severely ill women. Pregnancy did not increase the likelihood of successful discontinuation from antipanic medication. Conclusion: Impact of pregnancy on panic disorder is variable. Some patients, particularly those with milder symptoms, may improve during this time; more severely ill women may constitute a subgroup at risk for persistence of underlying disease and with a need for continued treatment with antipanic medication. RP COHEN, LS (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH-19445] NR 23 TC 42 Z9 42 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 1994 VL 55 IS 7 BP 284 EP 288 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PD432 UT WOS:A1994PD43200001 PM 7915272 ER PT J AU COHEN, LS SICHEL, DA DIMMOCK, JA ROSENBAUM, JF AF COHEN, LS SICHEL, DA DIMMOCK, JA ROSENBAUM, JF TI POSTPARTUM COURSE IN WOMEN WITH PREEXISTING PANIC DISORDER SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 146th Annual Meeting of the American-Psychiatric-Association CY MAY 27, 1993 CL SAN FRANCISCO, CA SP AMER PSYCHIAT ASSOC ID PREGNANCY; CHILDBEARING; DEPRESSION; PSYCHOSES AB Background: The postpartum period has typically been considered a time of risk for development of psychiatric disorder. Impact of the postpartum period on the course of anxiety disorders has not been characterized. This report describes the postpartum clinical course of 40 nondepressed women with preexisting panic disorder who were followed during pregnancy and the puerperium. Method: Through chart review and interview, we retrospectively evaluated the clinical course during the postpartum period of 40 women with pregravid panic disorder. Severity of illness, along with treatment received, was assessed from the third trimester of pregnancy to the twelfth postpartum week. Results: While 26 patients (65%) either maintained (N = 23) or improved (N = 3) clinical status, 14 patients (35%) demonstrated puerperal worsening. Those patients who received pharmacotherapy by Trimester 3 were significantly less likely to experience puerperal worsening of anxiety than those who did not receive treatment prior to the puerperium (p < .0001). Conclusion: The puerperium is a period of risk for some women with pregravid panic disorder. Antipanic medication may be prophylactic for those women at greatest risk. RP COHEN, LS (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,CLIN PSYCHOPHARMACOL UNIT,BOSTON,MA 02114, USA. FU NIMH NIH HHS [MH-19445] NR 26 TC 41 Z9 42 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 1994 VL 55 IS 7 BP 289 EP 292 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA PD432 UT WOS:A1994PD43200002 PM 7915273 ER PT J AU FU, Y NATHAN, DM LI, F LI, X FAUSTMAN, DL AF FU, Y NATHAN, DM LI, F LI, X FAUSTMAN, DL TI DEFECTIVE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION AN LYMPHOID-CELLS IN AUTOIMMUNITY SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Note C1 MASSACHUSETTS GEN HOSP,DIABET UNIT,IMMUNOBIOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP FU, Y (reprint author), MASSACHUSETTS GEN HOSP,DIABET UNIT,IMMUNOBIOL LABS,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD JUL-AUG PY 1994 VL 17 IS 7 BP 547 EP 547 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH547 UT WOS:A1994PH54700007 ER PT J AU FAUSTMAN, D COE, C AF FAUSTMAN, D COE, C TI PREVENTION OF XENOGRAFT REJECTION BY MASKING DONOR HLA CLASS-I ANTIGENS SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Note RP FAUSTMAN, D (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIABET UNIT,BOSTON,MA, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD JUL-AUG PY 1994 VL 17 IS 7 BP 553 EP 553 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH547 UT WOS:A1994PH54700010 ER PT J AU ZHANG, JZ DAVIDSON, I EISENBARTH, G WEINER, HL AF ZHANG, JZ DAVIDSON, I EISENBARTH, G WEINER, HL TI SUPPRESSION OF DIABETES IN NONOBESE DIABETIC MICE BY ORAL-ADMINISTRATION OF PORCINE INSULIN SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Note C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. RP ZHANG, JZ (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD JUL-AUG PY 1994 VL 17 IS 7 BP 573 EP 573 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PH547 UT WOS:A1994PH54700019 ER PT J AU BARTOLAZZI, A PEACH, R ARUFFO, A STAMENKOVIC, I AF BARTOLAZZI, A PEACH, R ARUFFO, A STAMENKOVIC, I TI INTERACTION BETWEEN CD44 AND HYALURONATE IS DIRECTLY IMPLICATED IN THE REGULATION OF TUMOR-DEVELOPMENT SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; T-CELL ACTIVATION; TRANSMEMBRANE GLYCOPROTEIN; EXTRACELLULAR DOMAIN; GROWTH INVIVO; CORE PROTEIN; ACID BINDING; EXPRESSION; MOLECULE; ADHESION AB CD44 is implicated in the regulation of tumor growth and metastasis but the mechanism by which expression of different CD44 isoforms determines the rate of primary and secondary tumor growth remains unclear. In the present study we use a human melanoma transfected with wild-type and mutant forms of CD44 to determine which functional property of the CD44 molecule is critical in influencing tumor behavior. We show that expression of a wild-type CD44 isoform that binds hyaluronic acid augments the rapidity of turner formation by melanoma cells in vivo, whereas expression of a CD44 mutant, which does not mediate cell attachment to hyaluronate, fails to do so. The importance of CD44-hyaluronate interaction in tumor development is underscored by the differential inhibitory effect of soluble wild-type and mutant CD44-Ig fusion proteins on melanoma growth in vivo. Whereas local administration of a mutant, nonhyaluronate binding, CD44-Ig fusion protein has no effect on subcutaneous melanoma growth in mice, infusion of wild-type CD44-Ig is shown to block tumor development. Taken together, these observations suggest that the tumor growth promoting property of CD44 is largely dependent on its ability to mediate cell attachment to hyaluronate. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP E,BOSTON,MA 02129. BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,SEATTLE,WA 98121. FU NCI NIH HHS [CA-55735] NR 46 TC 296 Z9 302 U1 1 U2 7 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 JUL 1 PY 1994 VL 180 IS 1 BP 53 EP 66 DI 10.1084/jem.180.1.53 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NR989 UT WOS:A1994NR98900009 PM 7516417 ER PT J AU XU, H GONZALO, JA STPIERRE, Y WILLIAMS, IR KUPPER, TS COTRAN, RS SPRINGER, TA GUTIERREZRAMOS, JC AF XU, H GONZALO, JA STPIERRE, Y WILLIAMS, IR KUPPER, TS COTRAN, RS SPRINGER, TA GUTIERREZRAMOS, JC TI LEUKOCYTOSIS AND RESISTANCE TO SEPTIC SHOCK IN INTERCELLULAR-ADHESION MOLECULE 1-DEFICIENT MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; LUNG VASCULAR INJURY; MONOCLONAL-ANTIBODY; COUNTER-RECEPTOR; IMMUNE-SYSTEM; ICAM-1 CD54; BACTERIAL-ENDOTOXINS; ANTIGEN-1 LFA-1; CD11B CD18; ACTIVATION AB Intercellular adhesion molecule 1 (ICAM-1) is one of three immunoglobulin superfamily members that bind to the integrins lymphocyte function associated 1 (LFA-1) and Mac-1 on leukocytes. We have generated mice that are genetically and functionally deficient in ICAM-1. These mice have elevated numbers of circulating neutrophils and lymphocytes, as well as diminished allogeneic T cell responses and delayed type hypersensitivity. Mutant mice are resistant to lethal effects of high doses of endotoxin (lipopolysaccharide [LPS]), and this correlates with a significant decrease in neutrophil infiltration in the liver. Production of inflammatory cytokines such as tumor necrosis factor ct or interleukin 1 is normal in ICAM-1-deficient mice, and thus protection appears to be related to a diminution in critical leukocyte-endothelial interactions. After sensitization with D-galactosamine (D-Gal), ICAM-1-deficient mice are resistant to the lethal effect of low doses of exotoxin (Staphylococcus aureus enterotoxin B [SEB]), which has been shown to mediate its toxic effects via the activation of specific T cells. In this model, ICAM-1-mediated protection against SEB lethality correlates with a decrease in the systemic release of inflammatory cytokines, as well as with prevention of extensive hepatocyte necrosis and hemorrhage. ICAM-1-deficient mice sensitized with D-Gal, however, are not protected from lethality when challenged with low doses of endotoxin (LPS). These studies show that the different contribution of ICAM-1 in the activation of either T cells or macrophages is decisive for the fatal outcome of the shock in these two models. This work suggests that anti-ICAM-1 therapy may be beneficial in both gram-positive and -negative septic shock, either by reducing T cell activation or by diminishing neutrophil infiltration. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. RI Williams, Ifor/D-3648-2011 OI Williams, Ifor/0000-0002-8810-2911 FU NHLBI NIH HHS [HL-36028, HL-48675]; PHS HHS [LA-31798] NR 69 TC 412 Z9 420 U1 0 U2 4 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 JUL 1 PY 1994 VL 180 IS 1 BP 95 EP 109 DI 10.1084/jem.180.1.95 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NR989 UT WOS:A1994NR98900013 PM 7911822 ER PT J AU NAKARAI, T ROBERTSON, MJ STREULI, M WU, ZN CIARDELLI, TL SMITH, KA RITZ, J AF NAKARAI, T ROBERTSON, MJ STREULI, M WU, ZN CIARDELLI, TL SMITH, KA RITZ, J TI INTERLEUKIN-2 RECEPTOR-GAMMA CHAIN EXPRESSION ON RESTING AND ACTIVATED LYMPHOID-CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; LEUKOCYTE COMMON ANTIGENS; IL-2 RECEPTOR; BETA-CHAIN; RECOMBINANT INTERLEUKIN-2; FUNCTIONAL COMPONENT; HUMAN-MONOCYTES; ALPHA-CHAIN; BINDING; INVIVO AB The interleukin 2 receptor (IL-2R) is known to be comprised of at least three genetically distinct subunits termed alpha, beta, and gamma. These chains can be expressed individually or in various combinations resulting in distinct receptors with different affinities for IL-2. In contrast to alpha and beta, the cell surface expression of the gamma chain protein previously has not been well-characterized. To examine cell surface expression of IL-2R gamma on hematopoietic cells, we developed two new monoclonal antibodies (mAbs) specific for this protein. Both 1A11 (immunoglobulin [IgG1]) and 3G11 (IgM) specifically reacted with murine cells transfected with IL-2R gamma cDNA, and immunoprecipitation studies indicated that both antibodies precipitated a protein of approximately 62-65 kD. Scatchard analysis of IL-2 binding to murine cells transfected with cDNA-encoding combinations of IL-2R components demonstrated that neither beta nor gamma chain bind IL-2 with measurable affinity, but coexpression of both beta and gamma is sufficient to form an intermediate affinity receptor. In the absence of gamma chain, beta chain interacts with alpha chain to form a ''pseudo-high'' affinity receptor. In contrast, gamma chain does not appear capable of interacting with alpha chain in the absence of beta chain. Thus, gamma chain appears to interact only with beta, but beta chain is capable of interacting with both alpha and gamma. Using the newly developed mAbs to examine cell surface expression by immunofluorescence, resting T cells were found to express low levels of gamma chain without detectable alpha or beta. Early after mitogen stimulation, T cells expressed higher levels of alpha, beta, and gamma. However, at later time points, T cells expressed alpha and gamma in marked excess over beta. Thus, formation of high affinity IL-2R on activated T cells was primarily limited by beta chain expression. In contrast, resting natural killer (NK) cells constitutively expressed IL-2R beta without detectable alpha or gamma. After activation with either IL-2 or IL-12, expression of both alpha and gamma transiently increased and then returned to very low levels. Expression of functional IL-2R on resting and activated NK cells, therefore, appeared to be primarily limited by the expression of gamma chain. IL-2 binding studies with resting NK cells confirmed the results of immunofluorescence studies indicating the presence of very low numbers of intermediate affinity (beta gamma) receptors for IL-2 on these cells. NK cells obtained from patients receiving IL-2 therapy were phenotypically similar to resting NK cells. These studies have identified marked differences in IL-2R composition in two different types of cytotoxic lymphocytes, further underscoring the complexity of this receptor/ligand system. With new reagents specific for IL-2R gamma, it will now be possible to examine further the functional significance of these differences. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. DARTMOUTH COLL,SCH MED,DEPT PHARMACOL & TOXICOL,HANOVER,NH 03755. VET ADM MED CTR,WHITE RIVER JCT,VT 05009. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV ALLERGY & IMMUNOL,NEW YORK,NY 10021. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA-41619]; NIAID NIH HHS [AI-34331] NR 43 TC 91 Z9 92 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 JUL 1 PY 1994 VL 180 IS 1 BP 241 EP 251 DI 10.1084/jem.180.1.241 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NR989 UT WOS:A1994NR98900027 PM 8006584 ER PT J AU OKADA, A MENDELSOHN, M ALT, F AF OKADA, A MENDELSOHN, M ALT, F TI DIFFERENTIAL ACTIVATION OF TRANSCRIPTION VERSUS RECOMBINATION OF TRANSGENIC T-CELL RECEPTOR-BETA VARIABLE REGION GENE SEGMENTS IN B-LINEAGE AND T-LINEAGE CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID BONE-MARROW; V(D)J RECOMBINATION; ORDERED REARRANGEMENT; PRECURSOR LYMPHOCYTES; PROTEIN-BINDING; CHAIN GENES; ENHANCER; EXPRESSION; DNA; METHYLATION AB We have tested the ability of the T cell receptor beta (TCR-beta) transcriptional enhancer (E(beta)) to confer transcriptional activation and tissue-specific V(D)J recombination of TCR-beta V, D, and J segments in a transgenic minilocus recombination substrate. We find that the minimal E(b)eta element, as previously shown for a DNA segment that contained the E mu element, promotes a high level of substrate D to J(beta) rearrangement in both B and T cells, but only promotes V-beta to DJ beta rearrangement in T cells. Thus, both the E(mu) and E(beta) elements similarly direct V(D)J recombination of this substrate in vivo, supporting a general role for transcriptional enhancers in the normal regulation of this rearrangement process. Surprisingly, however, we found that both the V-beta and DJ(beta) portion of the constructs were transcribed in an enhancer-dependent fashion (conferred by either E(mu) or E(beta)) in both B and T lineage cells, including normal precursor B cells propagated in culture. These findings indicate that, at least in some contexts, transcriptional activation, per se, is not sufficient to confer V(D)J recombinational accessibility to a substrate V gene segment, C1 CHILDRENS HOSP,HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NIAID NIH HHS [AI-20047, AI-31541] NR 55 TC 78 Z9 78 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 JUL 1 PY 1994 VL 180 IS 1 BP 261 EP 272 DI 10.1084/jem.180.1.261 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NR989 UT WOS:A1994NR98900029 PM 8006587 ER PT J AU JENIKE, MA AF JENIKE, MA TI NEUROLEPTIC MALIGNANT SYNDROME IN THE ELDERLY SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Editorial Material ID DANTROLENE; FREQUENCY; SODIUM C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 18 TC 0 Z9 0 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUL-SEP PY 1994 VL 7 IS 3 BP 195 EP 196 PG 2 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA PK903 UT WOS:A1994PK90300012 ER PT J AU JENIKE, M AF JENIKE, M TI ONSET OF TOURETTES-SYNDROME IN AN ELDERLY PATIENT SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 6 TC 0 Z9 0 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD JUL-SEP PY 1994 VL 7 IS 3 BP 196 EP 197 PG 2 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA PK903 UT WOS:A1994PK90300013 ER PT J AU GREENWALD, DP HONG, HZ MAY, JW AF GREENWALD, DP HONG, HZ MAY, JW TI MECHANICAL ANALYSIS OF TENDON SUTURE TECHNIQUES SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB The relative strengths of seven methods of tendon repair were measured by mechanical disruption in an effort to determine the quality of a technique using loaded criss-crossing sutures and a running epitenon stitch. Fifty-seven calcaneus tendons were harvested from adult New Zealand white rabbits and randomized for transection. Standardized oblique transections were repaired with nylon using modified Halsted peripheral suture; modified Kessler technique; Kessler core stitch alone; running peripheral epitenon stitch; modified Becker technique #1; modified Becker technique #2; and a new augmented Becker repair. Sixteen additional rabbits each had bilateral tendon repairs in situ, one leg by Kessler and the other by the new augmented Becker repair technique. Half were lethally injected after 2 weeks and half after 4 weeks. Tenorrhaphies were pulled apart at constant speed until a gap of 1 mm was observed. Strength (maximum stress) and toughness (energy absorption to gap formation) were calculated. At time 0 the new augmented Becker repairs were the strongest, followed by the Kessler and Becker #2 tenorrhaphies. Kessler repairs were weaker at 2 weeks and then gained in strength; new augmented Becker repairs did not weaken at the 2-week point and demonstrated significant gains in strength after 4 weeks in vivo. The new augmented Becker repair was the strongest by a significant margin at all time points. C1 MASSACHUSETTS GEN HOSP,DIV PLAST & RECONSTRUCT SURG,BOSTON,MA 02114. NR 0 TC 29 Z9 32 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 JUL PY 1994 VL 19A IS 4 BP 641 EP 647 DI 10.1016/0363-5023(94)90274-7 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA PA329 UT WOS:A1994PA32900023 PM 7963325 ER PT J AU MA, J WANG, JH SY, MS GUO, YJ HAUSER, C BIGBY, M AF MA, J WANG, JH SY, MS GUO, YJ HAUSER, C BIGBY, M TI TRINITROPHENOL REACTIVE T-CELL HYBRIDOMAS RECOGNIZE ANTIGENS THAT REQUIRE ANTIGEN-PROCESSING SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE ANTIGENS; CHLOROQUINE; HYBRIDOMAS; A20 ID FLUORESCEIN ISOTHIOCYANATE; DENDRITIC CELLS; PEPTIDES; MACROPHAGES; ACTIVATION; MEMBRANES; RECEPTOR; EPITOPES; IA AB Protein antigens must be taken up, processed, and displayed on the surface of antigen-presenting cells in association with major histocompatibility complex molecules before they can be recognized by T cells. Whether recognition of the haptens used to study allergic contact hypersensitivity in murine models similarly requires processing has not been determined. We analyzed whether presentation of trinitrophenol to trinitrophenol reactive T-cell hybridomas requires antigen processing by studying the effects of inhibitors of antigen processing and presentation on the ability of a syngeneic B-cell tumor (A20) to present trinitrophenol to a series of interleukin-2 producing, trinitrophenol specific, major histocompatibility complex class II-restricted T-cell hybridomas. The ability of trinitrophenol modified A20 cells to stimulate the hybridomas was completely inhibited by monoclonal, anti-trinitrophenol, or anti-Ia antibodies and was significantly reduced by paraformaldehyde fixation immediately after trinitrophenol modification. Trinitrophenol-modified A20 cultured at 37 degrees C for 2 h prior to fixation was significantly more effective at stimulating the hybridomas than trinitrophenol-modified A20 fixed immediately. The ability of A20 to present trinitrophenol was inhibited by chloroquine. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of trinitrophenol modified lymph node dendritic cells to stimulate the trinitrophenol specific hybridomas. Paraformaldehyde fixation and chloroquine treatment had similar effects on the ability of A20 cells to present ovalbumin to ovalbumin-specific hybridomas as they had on the ability of trinitrophenol modified A20 cells to present trinitrophenol to the trinitrophenol specific hybridomas. One of seven T-cell hybridomas responded to trinitrophenol modified ovalbumin but not other trinitrophenol modified proteins. These results suggest that, at least in part, T cells in the contact hypersensitivity response to trinitrophenol recognize antigens that require processing and that trinitrophenol modified proteins can be recognized. C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,BOSTON,MA 02114. UNIV GENEVA,HOP CANTONAL,DEPT DERMATOL,CH-1211 GENEVA,SWITZERLAND. FU NIAMS NIH HHS [AR39795-02] NR 34 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1994 VL 103 IS 1 BP 42 EP 48 DI 10.1111/1523-1747.ep12389535 PG 7 WC Dermatology SC Dermatology GA NW533 UT WOS:A1994NW53300010 PM 8027580 ER PT J AU COMPTON, C TONG, Y TROOKMAN, N ZHAO, HF ROY, D AF COMPTON, C TONG, Y TROOKMAN, N ZHAO, HF ROY, D TI TGF-BETA-1 GENE-EXPRESSION IN CULTURED HUMAN KERATINOCYTES DOES NOT DECREASE WITH BIOLOGIC AGE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE CULTURED EPITHELIAL GRAFT; NORTHERN HYBRIDIZATION; POLYMERASE CHAIN REACTION; WOUND HEALING ID GROWTH-FACTOR-BETA; HUMAN EPIDERMAL-CELLS; THICKNESS BURN WOUNDS; LEG ULCERS; INSITU HYBRIDIZATION; SKIN EQUIVALENTS; MESSENGER-RNA; Y-CHROMOSOME; TGF-BETA; ALLOGRAFTS AB The biologic activity of cultured epithelial grafts is believed to diminish with increasing cellular age. Therefore, keratinocytes from young donors are used preferentially in the production of cultured allografts for wound treatment. However, the impact of biologic age on cytokine gene expression by human keratinocytes has not been previously investigated. In this study, transforming growth factor-beta 1 (TGF-beta 1) gene expression in human keratinocytes derived from normal foreskins of males ranging in age from 7 months to 82 years was analyzed. Keratinocytes were harvested from fresh specimens and cultivated in vitro on 3T3 fibroblast feeder layers through second passage. The cells were analyzed both qualitatively and semiquantitatively for TGF-beta 1 gene expression using three separate techniques: in situ hybridization, Northern hybridization, and competitive polymerase chain reaction. By in situ hybridization, the signal representing TGF-beta 1 transcript was detected in cells in all layers of the stratified cultures, and immunohistochemical staining for TGF-beta 1 protein was equally intense in all layers. Northern blots of total RNA extracted from the cultivated cells showed no decrease in band density with increasing biologic age. Likewise, no decrease in TGF-beta 1 mRNA levels with biologic age was observed using a semiquantitative polymerase chain reaction assay. These results indicate that the potential for TGF-beta 1 gene expression in cultured foreskin keratinocytes does not decline with increasing cellular age. The findings imply that the clinical performance of cultured grafts, at least as it relates to the elaboration of this growth factor, may not be significantly altered by the biologic age of the keratinocyte donor. C1 SHRINERS HOSP CRIPPLED CHILDREN,BOSTON BURNS INST,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINOL UNIT,BOSTON,MA 02114. RP COMPTON, C (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,WARREN 2,15 FRUITE ST,BOSTON,MA 02114, USA. FU NIGMS NIH HHS [R01-GM35242] NR 55 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1994 VL 103 IS 1 BP 127 EP 133 DI 10.1111/1523-1747.ep12391899 PG 7 WC Dermatology SC Dermatology GA NW533 UT WOS:A1994NW53300026 PM 8027573 ER PT J AU BORREGAARD, N KJELDSEN, L SENGELOV, H DIAMOND, MS SPRINGER, TA ANDERSON, HC KISHIMOTO, TK BAINTON, DF AF BORREGAARD, N KJELDSEN, L SENGELOV, H DIAMOND, MS SPRINGER, TA ANDERSON, HC KISHIMOTO, TK BAINTON, DF TI CHANGES IN SUBCELLULAR-LOCALIZATION AND SURFACE EXPRESSION OF L-SELECTIN, ALKALINE-PHOSPHATASE, AND MAC-1 IN HUMAN NEUTROPHILS DURING STIMULATION WITH INFLAMMATORY MEDIATORS SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE FMLP; GM-CSF; IL-8; LTB(4); PAF; SECRETORY VESICLES; TNF ID LINKED-IMMUNOSORBENT-ASSAY; LEUKOCYTE ADHESION; INTRACELLULAR VESICLES; MONOCLONAL-ANTIBODY; MESENTERIC VENULES; ENDOTHELIAL-CELLS; PLASMA-MEMBRANE; INTEGRIN MAC-1; ACTIVATION; PROTEINS AB The localization of the adhesion protein L-selectin in human neutrophils was determined by subcellular fractionation and immunoelectron microscopy and compared with the localization of Mac-1 (alpha(m) beta(2)) and alkaline phosphatase, the marker for secretory vesicles. L-selectin was found to be localized exclusively on the plasma membrane of unstimulated cells and also of stimulated cells, although markedly diminished. This was in contrast to Mac-1, which was also localized in secretory vesicles and in specific/gelatinase granules as shown previously [Sengelov, H., et al. J. Clin. Invest. (1993) 92, 1467-1476]. Stimulation of neutrophils with inflammatory mediators such as tumor necrosis factor (TNF), platelet-activating factor (PAF), or f-Met-Leu-Phe (fMLP), induced parallel up-regulation of the surface membrane content of alkaline phosphatase and Mac-1 and down-regulation of L-selectin, as evidenced by flow cytometry. Preimbedding immunoelectron microscopy confirmed that L-selectin was present mainly on tips of microvilli in unstimulated cells and showed that alkaline phosphatase and Mac-1 were randomly distributed on the surface membrane of fMLP-stimulated cells. These studies indicate that the transition of neutrophils from L-selectin-presenting cells to Mac-1-presenting cells induced by inflammatory mediators is mediated by incorporation of secretory vesicle membrane, rich in Mac-1 and devoid of L-selectin, into the plasma membrane. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. UNIV KANSAS,MED CTR,DEPT PATHOL & ONCOL,KANSAS CITY,KS 66103. BOEHRINGER INGELHEIM PHARMACEUT INC,DEPT IMMUNOL,RIDGEFIELD,CT 06877. UNIV CALIF SAN FRANCISCO,DEPT PATHOL,SAN FRANCISCO,CA. RP BORREGAARD, N (reprint author), UNIV COPENHAGEN HOSP,RIGSHOSP,DEPT HEMATOL,GRANULOCYTE RES LAB,9 BLEGDANSVEJ,DK-2100 COPENHAGEN,DENMARK. FU NCI NIH HHS [CA 31799]; NIDDK NIH HHS [DK10486] NR 48 TC 165 Z9 170 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUL PY 1994 VL 56 IS 1 BP 80 EP 87 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA NV803 UT WOS:A1994NV80300012 PM 7517990 ER PT J AU GERARD, C GERARD, NP AF GERARD, C GERARD, NP TI MOLECULAR-BIOLOGY OF THE CLONED HUMAN PLATELET-ACTIVATING-FACTOR RECEPTOR SO JOURNAL OF LIPID MEDIATORS AND CELL SIGNALLING LA English DT Article DE PLATELET-ACTIVATING FACTOR; RECEPTORS; SIGNAL TRANSDUCTION; G-PROTEIN COUPLED RECEPTORS; COS CELL EXPRESSION ID EXPRESSION; CLONING AB The human platelet-activating receptor was cloned from the human myeloid U-937 cell line. The isolated cDNA was identical in the coding sequence with clones isolated contemporaneously by two other groups. In man the PAF receptor appears to be encoded by a single gene. When transfected into COS-7 cells or a derivative of the human renal epithelial 293 cells, TSA, the cDNA directs expression of a single high-affinity binding site for PAF that is indistinguishable from that seen on human myeloid cells. In the COS system, as has been shown for neutrophils, ligand uptake is markedly temperature dependent. In COS cells PAF uptake is dependent on the presence of the transfected receptor and is not activated by agents which activate protein kinase C. In contrast, TSA cells also display significant non-receptor-dependent ligand uptake. C1 BETH ISRAEL HOSP,CTR BLOOD RES,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,THORNDIKE LAB,BOSTON,MA 02115. RP GERARD, C (reprint author), CHILDRENS HOSP,INA SUE PERLMUTTER LAB,320 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0929-7855 J9 J LIPID MEDIAT CELL JI J. Lipid Mediat. Cell Signal. PD JUL PY 1994 VL 10 IS 1-2 BP 77 EP 80 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NW903 UT WOS:A1994NW90300026 ER PT J AU BUCHANAN, L HILDEBRANDT, N MACKINNON, GE AF BUCHANAN, L HILDEBRANDT, N MACKINNON, GE TI PHONOLOGICAL PROCESSING OF NONWORDS BY A DEEP DYSLEXIC PATIENT - A ROWSE IS IMPLICITLY A ROSE SO JOURNAL OF NEUROLINGUISTICS LA English DT Article ID WORD-RECOGNITION; ACTIVATION; NETWORK; LEXICON; ERRORS; ACCESS; PRINT; SOUND AB Recent work has shown that implicit phonological knowledge plays a role in the word recognition performance of deep dyslexics [Hilderbrandt, N. and Sokol, S.M. Reading and Writing, 5, 43-68, 1993; Katz, R. B. and Lanzoni, S. M. Quarterly Journal of Experimental Psychology 45, 575-608, 1992]. The results of the current study extend this examination to include the investigation of implicit knowledge of nonword phonology. The data from two lexical decision tasks indicate that nonword phonology is available for processing by a deep dyslexic patient in that she produced a significant pseudohomophone effect as well as semantic priming with pseudohomophone primes in lexical decision. C1 MASSACHUSETTS GEN HOSP,NEUROPSYCHOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP BUCHANAN, L (reprint author), UNIV WATERLOO,DEPT PSYCHOL,WATERLOO,ON N2L 3G1,CANADA. NR 44 TC 28 Z9 28 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD JUL PY 1994 VL 8 IS 3 BP 163 EP 181 DI 10.1016/0911-6044(94)90024-8 PG 19 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA QJ942 UT WOS:A1994QJ94200001 ER PT J AU CHENG, LY OUTTERBRIDGE, LV COVATTA, ND MARTENS, DA GORDON, JT DRATMAN, MB AF CHENG, LY OUTTERBRIDGE, LV COVATTA, ND MARTENS, DA GORDON, JT DRATMAN, MB TI FILM AUTORADIOGRAPHY IDENTIFIES UNIQUE FEATURES OF [I-125] 3,3',5'-(REVERSE) TRIIODOTHYRONINE TRANSPORT FROM BLOOD TO BRAIN SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; RETINOL-BINDING PROTEIN; THYROID-HORMONE ACTION; CHOROID-PLEXUS; RAT-BRAIN; REVERSE TRIIODOTHYRONINE; TRANSTHYRETIN SYNTHESIS; THYROXINE TRANSPORT; MEDIATED TRANSPORT; PRE-ALBUMIN AB I, Steady-state iodothyronine profiles in plasma are composed of thyroid gland-synthesized hormones (mainly thyroxine) and tissue iodothyronine metabolites (mainly triiodothyronine and reverse triiodothyronine) that have entered the bloodstream. The hormones circulate in noncovalently bound complexes with a panoply of carrier proteins. Transthyretin (TTR), the major high-affinity thyroid hormone binding protein in rat plasma, is formed in the liver. It is also actively and independently synthesized in choroid plexus, where its function as a chaperone of thyroid hormones from bloodstream to cerebrospinal fluid (CSF) is undergoing close scrutiny by several groups of investigators. Because TTR has high-affinity binding sites for both thyroxine and retinol binding protein, its potential role as a mediator of combined thyroid hormone and retinoic acid availability in brain is of further interest. 2. While they are in the free state relative to their binding proteins, iodothyronines in the cerebral circulation are putatively subject to transport across both the blood-brain barrier (BBB) and choroid plexus CSF barrier(CSFB) before entering the brain. Previous autoradiographic studies had already indicated that after intravenous administration the transport mechanisms governing thyroxine and triiodothyronine entry into brain were probably similar, whereas those for reverse triiodothyronine were very different, although the basis for the difference was not established at that time. Intense labeling seen over brain ventricles after intravenous administration of all three iodothyronines suggested that all were subject to transport across the CSFB. 3. To evaluate the role of the BBB and CSFB in determining iodothyronine access to brain parenchyma, autoradiograms prepared after intravenous administration of[I-125]-labeled hormones (revealing results of transport across both barriers) were compared with those prepared after intrathecal (icv) hormone injection (reflecting only their capacity to penetrate into the brain after successfully navigating the CSFB). 4. Those studies revealed that thyroxine and triiodothyronine were mainly transported across the BBB. They shared with reverse triiodothyronine a generally similar, limited pattern of penetration from CSF into the brain, with circumventricular organs likely to be the main recipients of iodothyronines (with or without retinol) transported across the CSFB. 5. Analysis of all of the images obtained after intravenous and icv hormone administration clarified the basis for the unique distribution of intravenously injected reverse triiodothyronine. The hormone is excluded by the BBB but may be subject to limited penetration into brain parenchyma via the CSF. 6. Overall the observations single out reverse triiodothyronine as the iodothyronine showing the most distinctive as well as the most limited pattern of transport from blood to brain. Although it is considered to be a largely inactive metabolic product formed in the service of thyroxine disposal, a number of considerations suggest that reverse triiodothyronine, actively formed from thyroxine within the brain at selected sites of inner ring monodeiodinase activity, may have as yet undiscovered functions. The present results raise the possibility that, as in the case of other known neuroactive molecules that are formed within the brain but excluded by the BBB, reverse triiodothyronine generated intracerebrally may exert important brain-specific and site-specific functional effects. C1 DEPT VET AFFAIRS MED CTR,MED RES SERV 151,PHILADELPHIA,PA 19104. MED COLL PENN,DEPT MED,PHILADELPHIA,PA 19129. UNIV PENN,DEPT MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. FU NIMH NIH HHS [MH-45252, MH-44210] NR 46 TC 16 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 1994 VL 72 IS 1 BP 380 EP 391 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA NX819 UT WOS:A1994NX81900034 PM 7965021 ER PT J AU ABRAHAM, SA EAGLE, KA AF ABRAHAM, SA EAGLE, KA TI PREOPERATIVE CARDIAC RISK ASSESSMENT FOR NONCARDIAC SURGERY SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Review DE PREOPERATIVE EVALUATION; CARDIAC RISK ASSESSMENT; DIPYRIDAMOLE THALLIUM SCINTIGRAPHY ID CORONARY-ARTERY DISEASE; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; DIPYRIDAMOLE-THALLIUM SCINTIGRAPHY; PERIPHERAL VASCULAR-DISEASE; INTRAVENOUS DIPYRIDAMOLE; VASODILATOR RESERVE; SURGICAL-PROCEDURES; PROGNOSTIC VALUE; EXERCISE; EVENTS AB Patients presenting for noncardiac surgery should receive careful preoperative cardiac risk stratification. This has implications not only for the perioperative period, but also for long-term survival. After an initial clinical evaluation, certain patients will be referred for noninvasive testing. Those without significant inducible ischemia at a high workload have a low risk for perioperative cardiac complictions. Patients who are unable to exercise adequately may require alternative forms of testing, of which dipyridamole thallium scintigraphy is the most thoroughly studied and validated option. Patients with either high-risk clinical profiles or significant thallium redistribution merit consideration for preoperative coronary angiography. Treatment options for high-risk patients include: (1) Proceeding with surgery as planned along with aggressive perioperative monitoring and anti-ischemic therapy, (2) coronary angiography with subsequent myocardial revascularization as appropriate before elective surgery, (3) selecting an alternative, lower risk surgical approach, and (4) cancellation of surgery in lieu of a trial of conservative therapy. C1 MASSACHUSETTS GEN HOSP,WANG AMBULATORY CARE CTR,CLIN CARDIOL UNIV,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 60 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD JUL-AUG PY 1994 VL 1 IS 4 BP 389 EP 398 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA PU849 UT WOS:A1994PU84900010 PM 9420722 ER PT J AU KALES, SN PENTIUC, F CHRISTIANI, DC AF KALES, SN PENTIUC, F CHRISTIANI, DC TI PSEUDOELEVATION OF CARBOXYHEMOGLOBIN LEVELS IN FIREFIGHTERS SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CORONARY-ARTERY DISEASE; CARBON-MONOXIDE; RAPID ESTIMATION; EXPOSURE AB Carbon monoxide is a common and potentially lethal exposure documented by an elevated carboxyhemoglobin (COHb) level. We conducted an investigation of unexpectedly high carboxyhemoglobin levels in a group of firefighters. Twelve of 34 (35%) nonsmokers tested had levels greater than 4% COHb and 9 of 34 (26%) had levels of 10% or higher. Quadruplicate blood samples from hospital staff and firefighters were sent in duplicate to the original laboratory, which used manual spectrophotometry, and to a second reference facility using a cooximeter. Cooximeter results were lower and also more reproducible. By cooximetry, all 24 nonsmoking firefighters retested had COHb levels less than 3%. Cooximetry is widely available and is the most suitable methodology in clinical situations. Spurious results despite the use of a large reference laboratory argue for the standardization of analytic methods for COHb among laboratories. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MASSACHUSETTS RESP HOSP,CAMBRIDGE,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP KALES, SN (reprint author), CAMBRIDGE HOSP,DEPT MED,1493 CAMBRIDGE ST,CAMBRIDGE,MA 02139, USA. FU PHS HHS [E500002] NR 18 TC 3 Z9 4 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUL PY 1994 VL 36 IS 7 BP 752 EP 756 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NZ586 UT WOS:A1994NZ58600011 PM 7931741 ER PT J AU CAPANO, G BLOCH, KJ SCHIFFRIN, EJ DASCOLI, JA ISRAEL, EJ HARMATZ, PR AF CAPANO, G BLOCH, KJ SCHIFFRIN, EJ DASCOLI, JA ISRAEL, EJ HARMATZ, PR TI INFLUENCE OF THE POLYAMINE, SPERMIDINE, ON INTESTINAL MATURATION AND DIETARY ANTIGEN UPTAKE IN THE NEONATAL RAT SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE POLYAMINE; SPERMIDINE; NEONATE; RAT; INTESTINE ID NONSPECIFIC MACROMOLECULAR ABSORPTION; EPIDERMAL GROWTH-FACTOR; EPITHELIAL-CELLS; INFANT FORMULAS; MUCOSAL GROWTH; SUCKLING RATS; NEWBORN RAT; TRANSPORT; BARRIER; IGG AB Polyamines appear to have an important role in postnatal growth of the rat intestine. In the present study, we examined the effect of spermidine on the maturation of the intestine and on its ability to exclude macromolecules. Two litters of Sprague-Dawley rat pups were assigned to one of four experimental groups. These groups received, on Days 7, 8, and 9, either (a) saline by gavage; (b) spermidine, 0.9 mg (6 mumol) by gavage; (c) cortisone acetate, 3.5 mg i.p.; or (d) saline i.p. On Day 10, animals were fed by gavage with a mixture of bovine serum albumin (BSA; 2 mg/g) and the gamma-globulin fraction of mouse antiovalbumin (anti-OVA) antiserum (1 mg/g) and were bled 4 h later. Intestinal tissues were processed for histologic examination, sucrase determination, and identification of neonatal intestinal Fc receptor (FcRn) by Western blot. Serum immunoreactive BSA (iBSA) and mouse IgG1 and IgG2a anti-OVA antibodies were estimated by enzyme-linked immunosorbent assay. Sucrase activity was elevated in cortisone- and spermidine-treated compared to control rats. iBSA and anti-OVA were significantly reduced in cortisone-treated compared to control rats but were not diminished significantly in the spermidine-treated animals. A decrease in the neonatal intestinal Fc receptor was apparent in the spermidine-fed group; cortisone produced a large reduction in FcRn. Spermidine-fed animals showed morphologic evidence of maturation, with loss of giant vacuoles in the distal intestine; cortisone did not produce significant changes in morphology. Thus, while spermidine, like cortisone, enhanced the appearance of the disaccharidase sucrase, it did not significantly reduce the uptake of BSA or IgG, which is usually observed in mature compared to immature animals. The reason for this dichotomy is not known. C1 CHILDRENS HOSP MED CTR NO CALIF, 747 52ND ST, OAKLAND, CA 94609 USA. MASSACHUSETTS GEN HOSP, COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, CLIN IMMUNOL UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, ALLERGY UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PEDIAT, BOSTON, MA 02115 USA. DEPT PEDIAT, NAPLES, ITALY. NESTLE SA, LAUSANNE, SWITZERLAND. FU NICHD NIH HHS [HD12437]; NIDDK NIH HHS [DK33506] NR 40 TC 42 Z9 43 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUL PY 1994 VL 19 IS 1 BP 34 EP 42 DI 10.1097/00005176-199407000-00006 PG 9 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA PA264 UT WOS:A1994PA26400006 PM 7965474 ER PT J AU ROSEN, FS AF ROSEN, FS TI JANEWAY,CHARLES,A SO JOURNAL OF PEDIATRICS LA English DT Biographical-Item RP ROSEN, FS (reprint author), HARVARD UNIV, SCH MED, CTR BLOOD RES, 800 HUNTINGTON AVE, BOSTON, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 1994 VL 125 IS 1 BP 167 EP 168 PG 2 WC Pediatrics SC Pediatrics GA NW317 UT WOS:A1994NW31700033 PM 8021770 ER PT J AU IMREY, PB CHILTON, NW PIHLSTROM, BL PROSKIN, HM KINGMAN, A LISTGARTEN, MA ZIMMERMAN, SO CIANCIO, SG COHEN, ME DAGOSTINO, RB FISCHMAN, SL FLEISS, JL GUNSOLLEY, JC KENT, RL KILLOY, WJ LASTER, LL MARKS, RG VARMA, AO AF IMREY, PB CHILTON, NW PIHLSTROM, BL PROSKIN, HM KINGMAN, A LISTGARTEN, MA ZIMMERMAN, SO CIANCIO, SG COHEN, ME DAGOSTINO, RB FISCHMAN, SL FLEISS, JL GUNSOLLEY, JC KENT, RL KILLOY, WJ LASTER, LL MARKS, RG VARMA, AO TI RECOMMENDED REVISIONS TO AMERICAN-DENTAL-ASSOCIATION GUIDELINES FOR ACCEPTANCE OF CHEMOTHERAPEUTIC PRODUCTS FOR GINGIVITIS CONTROL SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE GINGIVITIS; AMERICAN DENTAL ASSOCIATION; EFFICACY; CLINICAL TRIALS ID CHLORHEXIDINE AB This paper presents suggested revisions to the American Dental Association's 1985 guidelines for acceptance of anti-gingivitis chemotherapeutic agents. The areas of study design, choice and quality control of clinical gins measurements, statistical analysis, and minimum strength of effect, are addressed. The revisions articulate certain aspects of study design which were implicit in the 1985 guidelines, clarify language on cross-over designs and independence of studies, and recommend use of a United States population in at least one trial supporting a product. Separate recording and analysis of a product's effect on gingival bleeding is proposed, and quality control of clinical measurements receives enhanced emphasis. Modestly elaborated statistical reporting guidelines and strengthened approval criteria, based on size of estimated effect as well as statistical significance, are advocated. C1 UNIV ILLINOIS,DEPT MED INFORMAT SCI,URBANA,IL 61801. UNIV ILLINOIS,DEPT COMMUNITY HLTH STAT,URBANA,IL 61801. UNIV ILLINOIS,CTR RES ORAL MOLEC BIOL,URBANA,IL 61801. COLUMBIA UNIV,SCH DENT & ORAL SURG,NEW YORK,NY. COLUMBIA UNIV,DIV BIOSTAT,NEW YORK,NY. UNIV MINNESOTA,MINNESOTA CLIN DENT RES CTR,MINNEAPOLIS,MN 55455. EASTMAN DENT CTR,DIV BIOSTAT,ROCHESTER,NY. NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. UNIV PENN,EPIDEMIOL SECT,PHILADELPHIA,PA 19104. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,HOUSTON,TX 77030. SUNY BUFFALO,DEPT PERIODONTOL,BUFFALO,NY. SUNY BUFFALO,DEPT ORAL MED,BUFFALO,NY. USN,DENT RES INST,GREAT LAKES,IL. BOSTON UNIV,DEPT MATH,BOSTON,MA 02215. VIRGINIA COMMONWEALTH UNIV,DEPT PERIODONT,RICHMOND,VA. FORSYTH DENT CTR,BOSTON,MA 02115. UNIV MISSOURI,DEPT PERIODONT,KANSAS CITY,MO 64110. UNIV FLORIDA,DEPT STAT,DIV BIOSTAT,GAINESVILLE,FL 32611. SUNY STONY BROOK,DEPT PREVENT MED,STONY BROOK,NY 11794. UNIV PENN,DEPT PERIODONT,PHILADELPHIA,PA 19104. RP IMREY, PB (reprint author), UNIV ILLINOIS,TASK FORCE DESIGN & ANAL DENT & ORAL RES,190 MED SCI BLDG,506 S MATHEWS AVE,URBANA,IL 61801, USA. OI Imrey, Peter/0000-0002-0533-4603 NR 11 TC 23 Z9 24 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD JUL PY 1994 VL 29 IS 4 BP 299 EP 304 DI 10.1111/j.1600-0765.1994.tb01225.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PA409 UT WOS:A1994PA40900010 PM 7932024 ER PT J AU SCOTT, PA CHOU, JM TANG, H FRAZER, A AF SCOTT, PA CHOU, JM TANG, H FRAZER, A TI DIFFERENTIAL INDUCTION OF 5-HT1A-MEDIATED RESPONSES IN-VIVO BY 3 CHEMICALLY DISSIMILAR 5-HT1A AGONISTS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID POSTSYNAPTIC 5-HT(1A) RECEPTORS; MONOAMINE OXIDASE INHIBITOR; DORSAL RAPHE NEURONS; ELECTROPHYSIOLOGICAL EVIDENCE; L-TRYPTOPHAN; 5-HYDROXYTRYPTAMINE1A RECEPTORS; BEHAVIORAL SYNDROME; RAT-BRAIN; IN-VIVO; SEROTONIN AB In the rat, activation of 5-hydroxytryptamine(1A) (5-HT1A) receptors causes hypothermia and the 5-HT syndrome. The effects of three chemically dissimilar 5-HT1A agonists administered s.c. [8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), gepirone, and (+)4[n-5-(methoxychroman-3-yl)n-propylamino]butyl-8-azas-piro[4,5]decane-7,adione ((+) S-20499)] on both of these responses were studied. The same maximal drop in body temperature (similar to 2.5 degrees C) was elicited by all three agonists, 8-OH-DPAT being the most potent (EC(50) = 0.05 mg/kg), followed by gepirone (1.8 mg/kg) and (+) S-20499 (8 mg/kg). Both pindolol, a nonselective 5-HT1A receptor/beta adrenoceptor antagonist and n-t-butyl,- 3-[1-[4-(2-methoxy)phenyl]piperazinyl]-1-phenylpropionamide [(+) WAY 100135], a more selective 5-HT1A receptor antagonist, dose dependently attenuated the hypothermia induced by all three agonists. From these data, we inferred that all three agonists caused hypothermia via activation of 5-HT1A receptors. The syndrome was observed reliably in rats at doses of 2 to 4 mg/kg 8-OH-DPAT; doses up to 100 mg/kg of gepirone or (+) S-20499 did not produce the syndrome. In reserpine-pretreated animals, 8-OH-DPAT (maximal effect at 2-4 mg/kg) and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (5 mg/kg) induced forepaw treading, whereas gepirone (10 mg/kg) and (+) S-20499 (75 mg/kg) did not. (+) WAY 100135 competitively antagonized the forepaw treading caused by 8-OH-DPAT in reserpine-pretreated rats. This indicates that forepaw treading, like hypothermia, is mediated by activation of 5-HT1A receptors. Gepirone (5-10 mg/kg) attenuated the forepaw treading induced by either 3-OH-DPAT (4 mg/kg) or 5-MeODMT (5 mg/kg); by contrast, (+) S-20499, at doses up to 75 mg/kg, did not attenuate the forepaw treading induced by either 8-OH-DPAT or 5-MeODMT. The inability of (+) S-20499 either to induce the 5-HT syndrome or forepaw treading or to attenuate the forepaw treading induced by other agonists could be due to several factors, one of which is that different subtypes of the 5HT(1A) receptor mediate hypothermia and the 5-HT syndrome. C1 DEPT VET AFFAIRS MED CTR,NEUROPSYCHOPHARMACOL UNIT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DAVID MAHONEY INST NEUROL SCI,PHILADELPHIA,PA 19104. RP SCOTT, PA (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIMH NIH HHS [MH48125] NR 54 TC 38 Z9 38 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 1994 VL 270 IS 1 BP 198 EP 208 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PC025 UT WOS:A1994PC02500027 PM 8035316 ER PT J AU HARLEY, JB AF HARLEY, JB TI AUTOANTIBODIES ARE CENTRAL TO THE DIAGNOSIS AND CLINICAL MANIFESTATIONS OF LUPUS SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID DISEASE HETEROGENEITY; ERYTHEMATOSUS; PROTEIN C1 US DEPT VET AFFAIRS,OKLAHOMA CITY,OK. RP HARLEY, JB (reprint author), UNIV OKLAHOMA,OKLAHOMA MED RES FDN,OKLAHOMA CITY,OK, USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 1994 VL 21 IS 7 BP 1183 EP 1185 PG 3 WC Rheumatology SC Rheumatology GA NW809 UT WOS:A1994NW80900003 PM 7966055 ER PT J AU SARANTOS, P ABOUHAMZE, Z COPELAND, EM SOUBA, WW AF SARANTOS, P ABOUHAMZE, Z COPELAND, EM SOUBA, WW TI GLUCOCORTICOIDS REGULATE GLUTAMINASE GENE-EXPRESSION IN HUMAN INTESTINAL EPITHELIAL-CELLS SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 10-13, 1993 CL HERSHEY, PA SP ASSOC ACAD SURG ID METABOLISM; MONOLAYERS; CACO-2 AB Glutamine is essential for intestinal metabolism and function, but its circulating and luminal availability to the mucosa may be diminished during critical illness. We hypothesized that glucocorticoids, which are produced in increased amounts during critical illness, accelerate mucosal glutamine metabolism. We studied intestinal glutamine utilization by examining the regulation of glutaminase in vitro, the enterocyte's principal enzyme of glutamine metabolism. Differentiated confluent human enterocytic cells (Caco-2 cells) were incubated with dexamethasone. Glutaminase activity was assayed and mRNA was extracted. Glutaminase transcripts were labeled with a P-32-labeled glutaminase cDNA probe, quantitated by phosphoimaging, and normalized to beta-actin. Dose- and time-response studies were performed. Dexamethasone-treated cells were also incubated with actinomycin D and cycloheximide. Dexamethasone (DEX) increased mucosal glutaminase activity by 45%, with maximal response at 12 hr. This increase was dose-dependent and was significant at doses of 1 and 10 mu M. The dexamethasone-mediated increase in glutaminase activity was associated with a 40% increase in glutaminase mRNA. The DEX-induced increase in glutaminase activity was inhibited by actinomycin D and cycloheximide, indicating the requirement for de novo RNA and protein synthesis. Glucocorticoids stimulate glutamine metabolism in these human enterocytic cells by increasing the activity of glutaminase, a response that is preceded by an increase in gene transcription. This glucocorticoid-mediated increase in glutaminase activity may be a mechanism by which gut glutamine metabolism is maintained during critical illness when blood glutamine levels are diminished and food intake is often interrupted. (C) 1994 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP SARANTOS, P (reprint author), UNIV FLORIDA,COLL MED,DEPT SURG,GAINESVILLE,FL 32611, USA. FU PHS HHS [T32] NR 14 TC 13 Z9 13 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 1994 VL 57 IS 1 BP 227 EP 231 DI 10.1006/jsre.1994.1136 PG 5 WC Surgery SC Surgery GA NY009 UT WOS:A1994NY00900035 PM 8041144 ER PT J AU LANE, H WOZNIAK, J PERKELL, J AF LANE, H WOZNIAK, J PERKELL, J TI CHANGES IN VOICE-ONSET TIME IN SPEAKERS WITH COCHLEAR IMPLANTS SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID SPEECH PRODUCTION; LARYNGEAL BEHAVIOR; HEARING; CHILDREN AB Voice-onset time (VOT) and syllable duration were measured for the English plosives in /Cad/ (C=consonant) context spoken by four postlingually deafened recipients of multichannel (Ineraid) cochlear implants. Recordings were made of their speech before, and at intervals following, activation of the speech processors of their implants. Three patients reduced mean syllable duration following activation. Using measures of VOT and syllable duration from speakers with normal hearing [Volaitis and Miller, J. Acoust. Sec. Am, 92, 723-735 (1992)] and from the subjects of this study, VOT is shown to vary approximately linearly with syllable duration over the ranges produced here. Therefore, the VOT of each token was adjusted for the change in syllable duration of that token relative to the mean syllable duration in the first baseline session. This variable, labeled VOTc, was used to evaluate the effects on voicing of the speakers' renewed access to the voicing contrast provided by their implants. Preimplant, all four speakers characteristically uttered voiced plosives with too-short VOT, compared to the measures for hearing speakers. Voiceless plosive mean VOT was also abnormally short for two of the speakers, and close to normal for the remaining two. With some hearing restored, subjects made relatively few errors with respect to voicing when identifying plosives in listening tests, and three of the four speakers lengthened VOTc. The findings are interpreted as supporting the hypothesis that speakers use their hearing to calibrate mechanisms of speech production by monitoring the relations between their articulations and their acoustic output. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02114. NORTHEASTERN UNIV,BOSTON,MA 02115. RP LANE, H (reprint author), MIT,ELECTR RES LAB,ROOM 36-511,50 VASSAR ST,CAMBRIDGE,MA 02139, USA. FU NIDCD NIH HHS [NIDC DC 00361] NR 28 TC 16 Z9 19 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 1994 VL 96 IS 1 BP 56 EP 64 DI 10.1121/1.410442 PG 9 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA NW521 UT WOS:A1994NW52100006 PM 8064023 ER PT J AU BIEDERMAN, J MILBERGER, S FARAONE, SV GUITE, J WARBURTON, R AF BIEDERMAN, J MILBERGER, S FARAONE, SV GUITE, J WARBURTON, R TI ASSOCIATIONS BETWEEN CHILDHOOD ASTHMA AND ADHD - ISSUES OF PSYCHIATRIC COMORBIDITY AND FAMILIALITY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ATTENTION DEFICIT DISORDER; ASTHMA; RISK ID ATTENTION-DEFICIT DISORDER; ATOPIC DISORDERS; CHILDREN; THEOPHYLLINE; PERFORMANCE; BEHAVIOR AB Objective: In this paper we evaluate the association between asthma and attention-deficit hyperactivity disorder (ADHD), addressing issues of comorbidity and familiality by formulating and testing competing hypotheses. Method: Subjects were 6- to 17-year-old boys with DSM-III-R ADHD (N = 140) and normal controls (N = 120) and their first-degree relatives. Information on asthma was obtained from the mothers in a standardized manner blind to the proband's clinical status. Results: The risk for asthma did not meaningfully differ between ADHD and control children. Relatives of ADHD probands with and without asthma were at significantly greater risk for ADHD than relatives of normal controls. In contrast, the risk for asthma was significantly elevated only among relatives of children with ADHD plus asthma. Conclusions: These findings argue against a substantial etiological or pathophysiological relationship between the two conditions but suggest that ADHD and asthma are independently transmitted in families. Thus, the observation of ADHD symptoms in an asthmatic child should not be dismissed out of hand as being a consequence of asthma since many asthmatic ADHD children may actually have ADHD. C1 HARVARD UNIV,INST PSYCHIAT EPIDEMIOL & GENET,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,ACC725,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [NIMH RO1 MH-41314-01A2] NR 22 TC 58 Z9 60 U1 1 U2 4 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 JUL-AUG PY 1994 VL 33 IS 6 BP 842 EP 848 DI 10.1097/00004583-199407000-00010 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NU824 UT WOS:A1994NU82400010 PM 8083141 ER PT J AU SEMRUDCLIKEMAN, M FILIPEK, PA BIEDERMAN, J STEINGARD, R KENNEDY, D RENSHAW, P BEKKEN, K AF SEMRUDCLIKEMAN, M FILIPEK, PA BIEDERMAN, J STEINGARD, R KENNEDY, D RENSHAW, P BEKKEN, K TI ATTENTION-DEFICIT HYPERACTIVITY DISORDER - MAGNETIC-RESONANCE-IMAGING MORPHOMETRIC ANALYSIS OF THE CORPUS-CALLOSUM SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE ATTENTION-DEFICIT HYPERACTIVITY DISORDER; CORPUS CALLOSUM; MAGNETIC RESONANCE IMAGING ID DEVELOPMENTAL DYSLEXIA; SUSTAINED ATTENTION; CHILDREN; BRAIN; MORPHOLOGY; CHILDHOOD; ADULTS; MRI AB Objective: The following study seeks to document possible differences in corpus callosal area and shape between children with attention-deficit hyperactivity disorder (ADHD) and controls. Method: Fifteen carefully diagnosed right-handed male subjects with ADHD with overactivity symptomatology were compared to 15 right-handed male control subjects. The corpus callosum was divided into seven areas on the midsagittal slice of a magnetic resonance image with shape analysis also conducted. Results: An exploratory shape analysis showed no significant differences in shape between the groups. No group differences were found in the area, length, or anterior regions of the corpus callosum. The ADHD subjects were found to have significantly smaller posterior corpus callosum regions than the control group, with the splenium accounting for most of the variance between the groups. Conclusions: The splenial area ot the corpus callosum is smaller in children with ADHD than in a sample of normally developing children. These smaller areas may relate to commonly seen sustained attention deficits which in turn negatively impact on the development of more advanced levels of attention such as self-regulation. Further study of the regions surrounding the splenial area is suggested to determine whether they are correlated in size to the smaller corpus callosum. C1 CHILDRENS HOSP MED CTR,DEPT PSYCHIAT,BOSTON,MA 02115. MCLEAN HOSP,NEUROIMAGING UNIT,BELMONT,MA 02178. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR MORPHOMETR ANAL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROPSYCHOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. RP SEMRUDCLIKEMAN, M (reprint author), UNIV WASHINGTON,322 MILLER HALL,DQ-12,SEATTLE,WA 98195, USA. RI Kennedy, David/H-3627-2012 FU NIMH NIH HHS [MH 14275] NR 46 TC 177 Z9 180 U1 2 U2 7 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 JUL-AUG PY 1994 VL 33 IS 6 BP 875 EP 881 DI 10.1097/00004583-199407000-00014 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NU824 UT WOS:A1994NU82400014 PM 8083145 ER PT J AU RIORDAN, AT COHEN, C AF RIORDAN, AT COHEN, C TI TINEA-CAPITIS CAUSED BY TRICHOPHYTON-RUBRUM IN A 67-YEAR-OLD WOMAN WITH SYSTEMIC LUPUS-ERYTHEMATOSUS SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter RP RIORDAN, AT (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 1994 VL 31 IS 1 BP 138 EP 138 PG 1 WC Dermatology SC Dermatology GA NU956 UT WOS:A1994NU95600045 PM 8021365 ER PT J AU DEPRADA, JAV JIANG, L HANDSCHUMACHER, MD XIE, SW RIVERA, JM SCHWAMMENTHAL, E GUERRERO, JL WEYMAN, AE LEVINE, RA PICARD, MH AF DEPRADA, JAV JIANG, L HANDSCHUMACHER, MD XIE, SW RIVERA, JM SCHWAMMENTHAL, E GUERRERO, JL WEYMAN, AE LEVINE, RA PICARD, MH TI QUANTIFICATION OF PERICARDIAL-EFFUSIONS BY 3-DIMENSIONAL ECHOCARDIOGRAPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID 3-DIMENSIONAL ECHOCARDIOGRAPHY; VENTRICULAR VOLUME; VALIDATION; DIAGNOSIS AB Objectives. The purpose of this study was to examine the accuracy of three dimensional echocardiography for the quantification of asymmetric pericardial effusion volume and to compare this new technique with two-dimensional echocardiography. Background. Quantification of pericardial effusion by two- dimensional echocardiography relies on a symmetric distribution of the fluid. Three-dimensional echocardiography can quantitate volume without these limitations, but its accuracy for pericardial effusion volume has not yet been assessed. Methods. In six open chest dogs, 41 different asymmetrically distributed pericardial effusions of known volume were created by serial infusions of fluid through a pericardial catheter. The hearts were imaged using an automated echocardiographic method that integrates three-dimensional spatial and imaging data. The surfaces of the pericardial sac and heart were then reconstructed, and the volumes of pericardial effusions were calculated. Two-dimensional echocardiography was performed simultaneously, and volumes were calculated using the prolate ellipsoid method. Asymmetric distribution of the fluid was obtained by applying Localized hydrostatic pressure to the pericardium. Results. The volumes of pericardial effusion quantified using three dimensional echocardiography correlated well with actual volumes (y = 1.0x - 1.4, SEE = 7.7 ml, r = 0.98). Two-dimensional echocardiography had an acceptable correlation (y = 1.0x + 2.3, SEE = 23 ml, r = 0.84), but a marked degree of variation from the true value was observed for any individual measurement. Conclusions. Three dimensional echocardiography accurately quantifies pericardial effusion volume in vivo, even when the fluid is distributed asymmetrically, whereas two-dimensional echocardiography is less reliable. This new technique may be of clinical value in quantitating pericardial effusion, especially in the serial evaluation of asymmetric or loculated effusions. C1 MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 18 TC 16 Z9 16 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 JUL PY 1994 VL 24 IS 1 BP 254 EP 259 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH375 UT WOS:A1994PH37500038 ER PT J AU KUTNER, NG SCHECHTMAN, KB ORY, MG BAKER, DI MILLER, JP PROVINCE, MA ARFKEN, CL ROSSITER, J HORNBROOK, MC STEVENS, VJ WINGFIELD, DJ GREENLICK, MR TINETTI, ME CLAUS, EB HORWITZ, RI BUCHNER, DM WAGNER, EH DELATEUR, BJ CRESS, ME PRICE, R ABRASS, IB ESSELMAN, P MARGUERITA, T MULROW, CD GERETY, MB CORNELL, JE SATTIN, RW DENINO, LA KANTEN, D WOLF, SL GREEN, RC MCNEELY, E COOGLER, C FIATARONE, MA ONEILL, EF RYAN, ND CLEMENTS, KM LIPSITZ, LA KEHAYIAS, JJ ROBERTS, SB EVANS, WJ WALLACE, R ROSS, JE HUSTON, JC KUNDEL, CJ SELLBERG, MS WOLFSON, LI WHIPPLE, RH AMERMAN, PM JUDGE, JO DERBY, CA KING, MB HADLEY, EC TAMBOLI, A WEISS, S AF KUTNER, NG SCHECHTMAN, KB ORY, MG BAKER, DI MILLER, JP PROVINCE, MA ARFKEN, CL ROSSITER, J HORNBROOK, MC STEVENS, VJ WINGFIELD, DJ GREENLICK, MR TINETTI, ME CLAUS, EB HORWITZ, RI BUCHNER, DM WAGNER, EH DELATEUR, BJ CRESS, ME PRICE, R ABRASS, IB ESSELMAN, P MARGUERITA, T MULROW, CD GERETY, MB CORNELL, JE SATTIN, RW DENINO, LA KANTEN, D WOLF, SL GREEN, RC MCNEELY, E COOGLER, C FIATARONE, MA ONEILL, EF RYAN, ND CLEMENTS, KM LIPSITZ, LA KEHAYIAS, JJ ROBERTS, SB EVANS, WJ WALLACE, R ROSS, JE HUSTON, JC KUNDEL, CJ SELLBERG, MS WOLFSON, LI WHIPPLE, RH AMERMAN, PM JUDGE, JO DERBY, CA KING, MB HADLEY, EC TAMBOLI, A WEISS, S TI OLDER ADULTS PERCEPTIONS OF THEIR HEALTH AND FUNCTIONING IN RELATION TO SLEEP DISTURBANCE, FALLING, AND URINARY-INCONTINENCE SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the Gerontological-Society-of-America CY NOV 20, 1992 CL WASHINGTON, DC SP GERONTOL SOC AMER ID FICSIT TRIALS; INTERVENTIONS; DISORDERS; FRAILTY; ELDERS AB OBJECTIVE: To investigate variation in older adults' perceived health and functioning that is associated with self-reported sleep disturbance, falling, and urinary incontinence, controlling for self-reported depression, ambulation difficulty, number of chronic conditions, and subjects' sociodemographic characteristics. DESIGN: Multicenter prospective study (FICSIT). SETTING: Persons age 70 and older living in the community evaluated at baseline. PARTICIPANTS: 239 women, 113 men; mean age = 77. MEASUREMENTS: Sleep disturbance score based on EPESE questions, recent falls history (Y/N), incontinent episodes (Y/N), CES-D score, SIP Ambulation score, and 4 MOS SF-36 scale scores. RESULTS: Women were significantly more likely than men to report multiple conditions (sleep disturbance, falling, incontinence) and to report lower levels of functioning as measured by 3 of 4 SF-36 scales. In regression analyses, sleep disturbance and urinary incontinence were significant predictors of perceived limitation in usual role activities because of physical health problems. Depression and ambulation measures significantly predicted scores on all 4 SF-36 scales. CONCLUSIONS: Our analysis suggests that it is important to address depressive symptomatology and ambulation difficulty-which in turn are related to sleep disturbance, falling, and urinary incontinence-in efforts to enhance older adults' perceived health and functioning. C1 WASHINGTON UNIV,DIV BIOSTAT,ST LOUIS,MO. NIA,BETHESDA,MD 20892. YALE UNIV,SCH NURSING,NEW HAVEN,CT 06536. WASHINGTON UNIV,SCH MED,DIV BIOSTAT,ST LOUIS,MO 63130. KAISER PERMANENTE CTR HLTH RES,PORTLAND,OR. YALE UNIV,SCH MED,PROGRAM AGING,NEW HAVEN,CT 06520. WASHINGTON UNIV,DEPT HLTH SCI,ST LOUIS,MO 63130. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX. CTR DIS CONTROL & PREVENT,ATLANTA,GA. UNIV CONNECTICUT,CTR HLTH,DEPT NEUROL,STORRS,CT 06269. NIA,NCNR,BETHESDA,MD. HARVARD UNIV,SCH MED,HEBREW REHABIL CTR AGED,USDA HUMAN NUTR RES CTR AGING,CAMBRIDGE,MA. UNIV IOWA,IOWA CITY,IA 52242. UNIV IOWA,IOWA STATE UNIV SCI & TECHNOL,IOWA CITY,IA. RP KUTNER, NG (reprint author), EMORY UNIV,SCH MED,DEPT REHABIL MED,1441 CLIFTON RD NE,ATLANTA,GA 30322, USA. RI Wolf, Steven/F-6588-2010; OI Wolf, Steven/0000-0002-9446-8995; Miller, J Philip/0000-0003-4568-6846 FU NIA NIH HHS [U01-AG09089] NR 27 TC 42 Z9 44 U1 2 U2 3 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 JUL PY 1994 VL 42 IS 7 BP 757 EP 762 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NW339 UT WOS:A1994NW33900012 PM 8014352 ER PT J AU OSTERWEIL, D MULFORD, P SYNDULKO, K MARTIN, M AF OSTERWEIL, D MULFORD, P SYNDULKO, K MARTIN, M TI COGNITIVE FUNCTION IN OLD AND VERY OLD RESIDENTS OF A RESIDENTIAL FACILITY - RELATIONSHIP TO AGE, EDUCATION, AND DEMENTIA SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID MINI-MENTAL-STATE; COMMUNITY POPULATION; ALZHEIMERS-DISEASE; LIMITS; NORMS AB OBJECTIVE: To determine if age, education, and dementia status affect neuropsychological performance in old and very old frail residential care subjects. DESIGN: Descriptive study of performance at the time of preadmission assessment. SETTING: Jewish Home for the Aging, Reseda, California. PARTICIPANTS: 201 applicants to the Jewish Home for the Aging residential care setting. Mean age was 84.7 years; SD was 5.6. Ninety-five subjects were 84 years of age or younger, while 106 were age 85 and older. There were 141 nondemented, 21 demented, and 39 were possibly demented applicants. Levels of education were as follows: 0-4 years: n = 25; 5-8: n = 69; 9-12: n = 77; and, 13-20: n = 23. MEASUREMENTS: Independent variables were age, education, and dementia status. Outcome measures were Folstein MMSE, Inglis P-A Learning Test, Digit Span, Cube Copying, selected Boston Diagnostic Aphasia Exam subtests. RESULTS: Subjects with 0 to 4 years of education scored more poorly on cognitive tests than other subjects. The very old tended to score more poorly than the old. Neuropsychological tests discriminated between those with normal cognitive function, possible dementia, and established dementia. About one-third of nondemented elderly scored below the traditional impairment cut-off of 24 points on the Mini-Mental State Exam. CONCLUSIONS: Questions are raised about how to interpret the poorer cognitive performance of very old and often frail subjects, especially in long-term-care settings where there are fewer demands upon residents whose impairments might otherwise cause them more functional difficulty. C1 UNIV CALIF LOS ANGELES,DEPT MED,DIV GERIATR,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,NEUROL SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. RP OSTERWEIL, D (reprint author), JEWISH HOMES AGING,7150 TAMPA AVE,RESEDA,CA 91335, USA. FU NIA NIH HHS [NIA 1K08AG00259-01A1] NR 32 TC 43 Z9 44 U1 5 U2 5 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 JUL PY 1994 VL 42 IS 7 BP 766 EP 773 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NW339 UT WOS:A1994NW33900014 PM 8014354 ER PT J AU ROYALL, DR MAHURIN, R AF ROYALL, DR MAHURIN, R TI QUALITATIVE ASSESSMENT OF DEMENTIA SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID BEDSIDE ASSESSMENT; IMPAIRMENT C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. RP ROYALL, DR (reprint author), UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX, USA. NR 9 TC 2 Z9 2 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 1994 VL 42 IS 7 BP 798 EP 799 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NW339 UT WOS:A1994NW33900023 PM 8014361 ER PT J AU MANDELL, J PALTIEL, HJ PETERS, CA BENACERRAF, BR AF MANDELL, J PALTIEL, HJ PETERS, CA BENACERRAF, BR TI PRENATAL FINDINGS ASSOCIATED WITH A UNILATERAL NONFUNCTIONING OR ABSENT KIDNEY SO JOURNAL OF UROLOGY LA English DT Article DE KIDNEY; ULTRASONOGRAPHY, PRENATAL; ABNORMALITIES ID MULTICYSTIC-DYSPLASTIC KIDNEY; NATURAL-HISTORY; INUTERO AB Prenatal findings in infants who were postnatally found to have a unilaterally nonfunctioning cystic, dysplastic or absent kidney were evaluated to understand better the prenatal pathophysiology of these conditions. Of the 38 cases in which prenatal and postnatal renal imaging studies were done fetal renal conditions leading to postnatal dysplasia or absence included small echogenic kidneys in 3, typical multicystic dysplasia in 30, obstructive uropathy in 4 and perinephric urinoma in 1. Abnormalities were noted on postnatal imaging in 30% of the contralateral kidneys. Vesicoureteral reflux was the most commonly identified abnormality, occurring in 23% of the cases. C1 MASSACHUSETTS GEN HOSP,CHILDRENS HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP MANDELL, J (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,DIV UROL,BOSTON,MA 02114, USA. OI Peters, Craig/0000-0001-7598-0865 NR 9 TC 20 Z9 22 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 JUL PY 1994 VL 152 IS 1 BP 176 EP 178 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA NQ770 UT WOS:A1994NQ77000059 PM 8201660 ER PT J AU CAMBRIA, RP BREWSTER, DC LITALIEN, GJ MONCURE, A DARLING, RC GERTLER, JP LAMURAGLIA, GM ATAMIAN, S ABBOTT, WM AF CAMBRIA, RP BREWSTER, DC LITALIEN, GJ MONCURE, A DARLING, RC GERTLER, JP LAMURAGLIA, GM ATAMIAN, S ABBOTT, WM TI THE DURABILITY OF DIFFERENT RECONSTRUCTIVE TECHNIQUES FOR ATHEROSCLEROTIC RENAL-ARTERY DISEASE SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID RENOVASCULAR HYPERTENSION; SURGICAL-TREATMENT; ANEURYSM REPAIR; NATURAL-HISTORY; AORTIC-SURGERY; RISK-FACTORS; REVASCULARIZATION; EXPERIENCE; SURVIVAL; TERM AB Purpose: Among various surgical techniques for renal artery reconstruction (RAX), anatomic aortorenal bypass has been the preferred standard. Yet concern regarding origin of the bypass from a diseased aorta and desire to avoid a major aortic operation in these patients who are often at poor risk has led to increasing use of extraanatomic bypass grafting, particularly hepatorenal and splenorenal bypass. This study was conducted to compare the safety and long-term performance of these different techniques of renal artery reconstruction. Methods: We reviewed a 15-year (1976 to 1991) experience with 323 surgical RAR performed in 285 patients with atherosclerotic renovascular disease. Long-term patency and survival rates were analyzed by life-table methods. Variables potentially affecting early failure of the RAR and perioperative and late mortality rates were examined by Cox proportional hazards models. Results: Diffuse atherosclerosis characterized the patients' clinical profile. Clinically evident coronary artery disease was present in 54% of patients, and some degree of renal insufficiency was present in 60%. Ninety-five percent of patients had hypertension with poor control of hypertension seen in 50%. Aortic disease necessitated combined aortic grafting and RAR in 43% of the study group. Various techniques of RAR were used as follows: endarterectomy or patch angioplasty, 8.5%; extraanatomic bypass grafting, 37% (hepatorenal, 62; splenorenal, 52; iliorenal, 7); and aortorenal bypass grafting, 54% (native aorta, 34; combined aortic graft and RAR, 140). Early failure of the RAR occurred in 5% of cases, and the operative mortality rate for the entire cohort was 5.6%. Median follow-up duration was 9.4 years. A comparison of early and late patency for the major types of RAR revealed equivalent (p = 0.44) performance of aortorenal and extraanatomic bypass grafting. Perioperative complications occurred more frequently (p < 0.02) in patients undergoing combined operations. The cumulative 5-year survival rate for all patients was 75%. Conclusions: Because extraanatomic bypass grafting can provide long-term results equivalent to aortorenal bypass grafting, the choice among techniques for RAR in patients with diffuse atherosclerosis should be based on both technical and operative safety considerations, rather than adherence to aortorenal bypass grafting as an inherently superior technique. C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DIV VASC SURG,BOSTON,MA 02114. NR 38 TC 71 Z9 74 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 1994 VL 20 IS 1 BP 76 EP 87 PG 12 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA NX379 UT WOS:A1994NX37900011 PM 8028093 ER PT J AU BARADARAN, K DABROWSKI, CE SCHAFFER, PA AF BARADARAN, K DABROWSKI, CE SCHAFFER, PA TI TRANSCRIPTIONAL ANALYSIS OF THE REGION OF THE HERPES-SIMPLEX VIRUS TYPE-1 GENOME CONTAINING THE UL8, UL9, AND UL10 GENES AND IDENTIFICATION OF A NOVEL DELAYED-EARLY GENE-PRODUCT, OBPC SO JOURNAL OF VIROLOGY LA English DT Article ID ORIGIN-BINDING-PROTEIN; VIRAL-DNA REPLICATION; ELECTROPHORETIC TRANSFER; POLYACRYLAMIDE GELS; POLYMERASE GENE; CONTROL SIGNALS; MESSENGER-RNA; EXPRESSION; PROMOTER; SEQUENCE AB The region of the UL component of the herpes simplex virus type 1 genome between nucleotides 17,793 and 25,150 includes three open reading frames that code for the protein products of the UL8, UL9, and UL10 genes (D. J. McGeogh, M. A. Dalrymple, A. J. Davison, A. Dolan, M. C. Frame, D. McNab, L. J. Ferry, J. E. Scott, and P. Taylor, J. Gen. Virol. 69:1531-1574, 1988). We have mapped and characterized the overlapping transcripts in this region and have found that, in addition to the low-abundance UL8 and UL9 transcripts and the abundant UL10 transcript, at least two additional transcription units, designated UL8.5 and UL9.5, are specified by this region of the genome. The 5' ends of the UL8, UL8.5, and UL9 transcripts were mapped to nucleotides 20,682, 22,351, and 23,381, respectively. The 5' terminus of the VL9.5 transcript has not yet been mapped. The 3' ends of the UL8, UL8.5, UL9, and UL9.5 transcripts are coterminal at nucleotide 18,197. The 5' end of the UL10 mRNA, which is transcribed from the strand opposite that specifying the UL8, UL8.5, UL9, and UL9.5 transcripts, lies within the UL9 open reading frame at nucleotide 22,944, while the 3' terminus was mapped to nucleotide 24,666. Time course studies demonstrated that the UL8 and UL9 transcripts are members of the early kinetic class, the UL8.5 mRNA is a delayed-early transcript, and the UL9.5 and UL10 transcripts belong to the true-late kinetic class. Examination of the nucleotide sequence of the UL8.5 transcript revealed a potential open reading frame that overlaps and is in frame with the C-terminal half of the open reading frame encoding the origin-binding protein (OBP), the product of the UL9 gene, In vitro translation of the UL8.5 transcript demonstrated that it encodes a protein with an apparent molecular mass of 53 M)a. This protein was recognized by antibody directed against the C-terminal region of OBP and has thus been designated OBPC. A protein with an identical apparent molecular mass was also recognized by this antibody in infected-cell lysates, indicating that OBPC is synthesized during viral infection. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,COMM VIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA08749, 5 T32 CA9031]; NIAID NIH HHS [R01 AI28537] NR 76 TC 51 Z9 51 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 JUL PY 1994 VL 68 IS 7 BP 4251 EP 4261 PG 11 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300015 PM 8207800 ER PT J AU GELBARD, HA NOTTET, HSLM SWINDELLS, S JETT, M DZENKO, KA GENIS, P WHITE, R WANG, L CHOI, YB ZHANG, DX LIPTON, SA TOURTELLOTTE, WW EPSTEIN, LG GENDELMAN, HE AF GELBARD, HA NOTTET, HSLM SWINDELLS, S JETT, M DZENKO, KA GENIS, P WHITE, R WANG, L CHOI, YB ZHANG, DX LIPTON, SA TOURTELLOTTE, WW EPSTEIN, LG GENDELMAN, HE TI PLATELET-ACTIVATING-FACTOR - A CANDIDATE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INDUCED NEUROTOXIN SO JOURNAL OF VIROLOGY LA English DT Article ID RECEPTOR-MEDIATED NEUROTOXICITY; SIGNAL TRANSDUCTION MECHANISMS; TUMOR-NECROSIS-FACTOR; ARACHIDONIC-ACID; INFECTED MACROPHAGES; HIPPOCAMPAL-NEURONS; NMDA RESPONSES; NERVOUS-SYSTEM; FRONTAL-CORTEX; GANGLION-CELLS AB The pathogenesis of central nervous system disease during human immunodeficiency virus type 1 (HIV-1) infection revolves around productive viral infection of brain macrophages and microglia. Neuronal losses in the cortex and subcortical gray matter accompany macrophage infection. The question of how viral infection of brain macrophages ultimately leads to central nervous system (CNS) pathology remains unanswered. Our previous work demonstrated high-level production of tumor necrosis factor alpha, interleukin 1 beta, arachidonic acid metabolites, and platelet-activating factor (PAF) from HIV-infected monocytes and astroglia (H. E. Gendelman, P. Genis, M. Jett, and H. S. L. M. Nottet, in E. Major, ed., Technical Advances in AIDS Research in the Nervous System, in press; P. Genis, M. Jett, E. W. Bernton, H. A. Gelbard, K. Dzenko, R. Keane, L. Resnick, D. J. Volsky, L. G. Epstein, and H. E. Gendelmal, J. Exp. Med. 176:1703-1718, 1992). These factors, together, were neurotoxic. The relative role(s) of each of these candidate neurotoxins in HIV-1-related CNS dysfunction was not unraveled by these initial experiments. We now report that PAF is produced during HIV-1-infected monocyte-astroglia interactions. PAF was detected at high levels in CSF of HIV-1-infected patients with immunosuppression and signs of CNS dysfunction. The biologic significance of the results for neurological disease was determined by addition of PAF to cultures of primary human fetal cortical or rat postnatal retinal ganglion neurons. Here, PAF at concentrations of greater than or equal to 300 pg/ml produced neuronal death. The N-methyl-D-aspartate receptor antagonist MK-801 or memantine partially blocked the neurotoxic effects of PAF. The identification of PAF as an HIV-1-induced neurotoxin provides ne,v insights into how HIV-1 causes neurological impairment and how it may ultimately be ameliorated. C1 UNIV ROCHESTER,MED CTR,DEPT NEUROL,DIV CHILD NEUROL,ROCHESTER,NY 14642. UNIV ROCHESTER,MED CTR,DEPT PEDIAT,ROCHESTER,NY 14642. UNIV ROCHESTER,MED CTR,DEPT MICROBIOL & IMMUNOL,ROCHESTER,NY 14642. UNIV NEBRASKA,MED CTR,DEPT MED,VIRAL PATHOGENESIS LAB,OMAHA,NE 68198. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. UNIV NEBRASKA,MED CTR,EPPLEY INST RES CANC & ALLIED DIS,OMAHA,NE 68198. WALTER REED ARMY INST RES,DIV MOLEC PATHOL,WASHINGTON,DC. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS BETH ISRAEL HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. VET ADM MED CTR,WADSWORTH DIV,NATL NEUROL RES SPECIMEN BANK,LOS ANGELES,CA 90073. VET ADM MED CTR,BRENTWOOD DIV,NATL NEUROL RES SPECIMEN BANK,LOS ANGELES,CA 90073. FU NEI NIH HHS [R01 EY09024-03]; NHLBI NIH HHS [R01 HL043628]; NICHD NIH HHS [P01 HD29587-01]; NIDA NIH HHS [R01 DA017618]; NINDS NIH HHS [P01 NS31492-01, P01 NS031492] NR 62 TC 290 Z9 302 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 JUL PY 1994 VL 68 IS 7 BP 4628 EP 4635 PG 8 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300057 PM 8207837 ER PT J AU CAO, J VASIR, B SODROSKI, JG AF CAO, J VASIR, B SODROSKI, JG TI CHANGES IN THE CYTOPATHIC EFFECTS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ASSOCIATED WITH A SINGLE AMINO-ACID ALTERATION IN THE ECTODOMAIN OF THE GP41 TRANSMEMBRANE GLYCOPROTEIN SO JOURNAL OF VIROLOGY LA English DT Note ID HTLV-III/LAV ENVELOPE; SYNCYTIUM FORMATION; MEMBRANE-FUSION; T4 MOLECULE; AIDS PATIENTS; CELL-FUSION; DOMAIN; HIV-1; RETROVIRUS; PROTEIN AB A human immunodeficiency virus type 1 mutant with a single amino acid change (designated 596 W/M) in the ectodomain of the gp41 transmembrane envelope glycoprotein replicated in T-cell lines and in CD4-positive peripheral blood mononuclear cells identically to the wild-type virus. However, the cytopathic effects associated with infection by the mutant virus were altered, with a marked attenuation of syncytium formation and a significant delay in single-cell lysis relative to those of the wild-type virus-infected culture. The 596 W/M mutant is apparently defective in a function that is dispensable for virus entry but that contributes to the efficiency of induction of viral cytopathic effects. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATH,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI24755, AI28691] NR 43 TC 22 Z9 22 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 JUL PY 1994 VL 68 IS 7 BP 4662 EP 4668 PG 7 WC Virology SC Virology GA NQ763 UT WOS:A1994NQ76300062 PM 8207841 ER PT J AU GREGERMAN, RI AF GREGERMAN, RI TI AGING AND HORMONE-SENSITIVE LIPOLYSIS - RECONCILING THE LITERATURE SO JOURNALS OF GERONTOLOGY LA English DT Review ID DEPENDENT PROTEIN-KINASE; RAT ADIPOCYTES; STIMULATED LIPOLYSIS; ADIPOSE-TISSUE; AGE; INHIBITION; ADENOSINE; RABBITS C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. RP GREGERMAN, RI (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,GRECC 182,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 16 TC 16 Z9 16 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 JUL PY 1994 VL 49 IS 4 BP B135 EP B139 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NV799 UT WOS:A1994NV79900001 PM 8014384 ER PT J AU ODENHEIMER, GL BEAUDET, M JETTE, AM ALBERT, MS GRANDE, L MINAKER, KL AF ODENHEIMER, GL BEAUDET, M JETTE, AM ALBERT, MS GRANDE, L MINAKER, KL TI PERFORMANCE-BASED DRIVING EVALUATION OF THE ELDERLY DRIVER - SAFETY, RELIABILITY, AND VALIDITY SO JOURNALS OF GERONTOLOGY LA English DT Article ID CEREBRAL-DAMAGE; DEMENTIA; SKILLS AB Background. Our driving population is aging and faces increased risk for injury and death from motor vehicle crashes. Clinicians are often asked to judge the driving safety of their patients without adequate guidelines. This article describes the development of a systematic performance-based road test for measuring driving skills of elderly drivers and its correlation with cognitive measures. Methods. This was a prospective, masked, observational study in which a driving instructor's global scores (''criterion standard'') and cognitive test scores were correlated with research driving scores created by two independent research raters sitting in the back seat of the car during each driving test. A convenience sample of 30 licensed drivers with a broad range of cognitive skills, over age 60, were studied on a closed course and in traffic. Results. Statistically significant correlations were observed between the ''criterion standard'' and closed course scores (r = .35, p < .05) and between the ''criterion standard'' and in-traffic scores (r = .64, p < .01). Significant correlations were obtained between in-traffic and cognitive test scores, e.g., Mini-Mental State Exam (r = .72, p < .01). Inter-rater reliability on the closed course was .84 and on the in-traffic component was .74. Internal consistency for the closed course was .78 and for in-traffic was .89. Conclusion. This study documented the safety, reliability, and validity of a systematic road test for elderly drivers with a range of cognitive skills. Larger studies are needed to determine the cognitive factors that independently predict driving performance. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. HARVARD UNIV,SCH MED,DEPT PSYCHIAT & NEUROL,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP ODENHEIMER, GL (reprint author), HARVARD UNIV,SCH MED,BROCKTON W ROXBURY VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,BOSTON,MA 02132, USA. NR 23 TC 93 Z9 94 U1 2 U2 11 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 JUL PY 1994 VL 49 IS 4 BP M153 EP M159 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NV799 UT WOS:A1994NV79900007 PM 8014389 ER PT J AU CHOUDHURY, GG BISWAS, P GRANDALIANO, G FOUQUERAY, B HARVEY, SA ABBOUD, HE AF CHOUDHURY, GG BISWAS, P GRANDALIANO, G FOUQUERAY, B HARVEY, SA ABBOUD, HE TI PDGF-MEDIATED ACTIVATION OF PHOSPHATIDYLINOSITOL 3-KINASE IN HUMAN MESANGIAL CELLS SO KIDNEY INTERNATIONAL LA English DT Article ID RECEPTOR TYROSINE KINASES; GROWTH-FACTOR RECEPTORS; PHOSPHOLIPASE-C-GAMMA; MIDDLE T-ANTIGEN; HUMAN PLATELETS; SH3 DOMAINS; SIGNAL TRANSDUCTION; PROTEIN; BINDING; PHOSPHORYLATION AB Platelet-derived growth factor (PDGF) stimulates mitogenesis and exerts other biologic activities in glomerular mesangial cells. The precise mechanism of PDGF-induced mitogenesis in these cells is not clear. The activation of a signal transducing enzyme, phosphatidylinositol 3 kinase (PI 3 kinase) is associated with mitogenesis. Activation of PI 3 kinase results from stimulation of tyrosine kinase and G-protein-coupled classes of receptors. The synthesis of D3 phosphorylated inositides, the products of this enzymatic reaction, in non-nucleated cells such as blood platelets is dependent upon protein kinase C activation and G-proteins. We studied the activation of PI 3 kinase in response to PDGF in human glomerular mesangial cells. Using a PI 3 kinase 85 kD subunit specific antibody, we detected mesangial cell PI 3 kinase protein as 110 and 85 kD heterodimer. PDGF stimulated PI 3 kinase activity in antiphosphotyrosine immunoprecipitates in a dose-dependent manner showing maximum activation at 12 ng/ml. The antiphosphotyrosine associated PI 3 kinase activity showed biphasic kinetics with a fast peak within two minutes followed by a second peak at 10 minutes. Antiphosphotyrosine and PI 3 kinase immunoprecipitation studies indicated the association of the 85 kD PI 3 kinase subunit with PDGFR. Direct immunoprecipitation with PDGFR beta antibody showed the association of PI 3 kinase activity with the PDGF-receptor. The isoquinoline sulfonyl piperazine compound H7 at concentrations that inhibit PDGF-stimulated PKC activity had no effect on PDGF-stimulated PI 3 kinase activity in antiphospotyrosine immunoprecipates. These data indicate that PI3 kinase activation is insensitive to PKC. Treatment of mesangial cells with pertussis toxin at concentrations that partially inhibited PDGF-induced DNA synthesis in human mesangial cells did not inhibit PDGF-induced PI 3 kinase activation. These data indicate that PDGF activates PI 3 kinase in mesangial cells and that pertussis toxin-sensitive G-proteins are not involved in PI 3 kinase activation. The data further dissociate activation of PI 3 kinase from mitogenesis in human mesangial cells. C1 UNIV TEXAS,HLTH SCI CTR,DEPT BIOCHEM,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP CHOUDHURY, GG (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV NEPHROL,SAN ANTONIO,TX 78284, USA. RI Grandaliano, Giuseppe/G-2963-2012 FU NIDDK NIH HHS [DK 43988, DK 33665] NR 49 TC 33 Z9 34 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1994 VL 46 IS 1 BP 37 EP 47 DI 10.1038/ki.1994.242 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA NT128 UT WOS:A1994NT12800005 PM 7933847 ER PT J AU KREISBERG, JI RADNIK, RA AYO, SH GARONI, JA SAIKUMAR, P AF KREISBERG, JI RADNIK, RA AYO, SH GARONI, JA SAIKUMAR, P TI HIGH GLUCOSE ELEVATES C-FOS AND C-JUN TRANSCRIPTS AND PROTEINS IN MESANGIAL CELL-CULTURES SO KIDNEY INTERNATIONAL LA English DT Article ID GENE-EXPRESSION; DIACYLGLYCEROL MASS; SIGNAL TRANSDUCTION; DIABETES-MELLITUS; MESSENGER-RNA; KINASE-C; ACTIVATION; GLOMERULI; ONCOGENES; INCREASE AB It has been previously shown that rat glomerular mesangial cells synthesized increased amounts of fibronectin, laminin, and type IV collagen when grown in medium containing 30 mM glucose. High glucose exerted its effect at the mRNA level since transcripts for all three extracellular matrix (ECM) proteins were similarly elevated. High glucose appeared to exert its effect on ECM mRNA levels through protein kinase C activation. Using quantitative reverse transcription (RT) PCR, we now report that mRNA levels for c-fos and c-Jun were increased approximately twofold after treatment with high glucose. The fos levels were elevated 15 minutes after addition of high glucose and were maintained elevated through 30 minutes; by one hour mRNA levels for fos returned to control levels, c-jun, on the other hand, was increased at two hours and remained elevated at 24 and 48 hours. Fibronectin mRNA levels were increased three- to fourfold at 24 and 48 hours. Immunofluorescence studies with polyclonal antibodies to c-fos and c-jun revealed that high glucose treatment for four hours increased nuclear staining intensity two- to threefold for both proteins. Nuclear staining for fos returned to control levels by 24 hours while staining for jun remained elevated. These determinations were made on images obtained on a confocal laser scanning microscope. Thus, high glucose may effect gene expression of ECM proteins by elevating the transcription factors c-fos and c-jun which complex with one another to form activator protein 1 (AP-1). C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP KREISBERG, JI (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIDDK NIH HHS [DK 29787] NR 28 TC 103 Z9 105 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1994 VL 46 IS 1 BP 105 EP 112 DI 10.1038/ki.1994.249 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA NT128 UT WOS:A1994NT12800012 PM 7933827 ER PT J AU LEWANDROWSKI, K BAILEY, E DHANAK, E LAPOSATA, M FLOOD, J AF LEWANDROWSKI, K BAILEY, E DHANAK, E LAPOSATA, M FLOOD, J TI MANDATORY LABORATORY CONSULTATION - HOW ONE HOSPITALS PROGRAM REDUCED OVERUSE OF CARDIAC TESTS SO LABORATORY MEDICINE LA English DT Article AB We retrospectively analyzed test use patterns during a 4-year period before and after institution of a mandatory laboratory approval program for lactate dehydrogenase isoenzyme analysis. In the first month after institution of the program, requests for lactate dehydrogenase isoenzymes declined from about 2,000 per month to 7 per month (greater than 99% decrease) and remained stable for 2 years. The decrease in lactate dehydrogenase isoenzyme requests did not result in any significant change in requests for creatine kinase or creatine kinase MB isoenzyme, and total lactase dehydrogenase requests (relative to creatine kinase requests) were reduced. Of the remaining lactate dehydrogenase isoenzyme tests that were performed, most were normal or nondiagnostic. RP LEWANDROWSKI, K (reprint author), MASSACHUSETTS GEN HOSP,GRAY 5,BOSTON,MA 02114, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 SN 0007-5027 J9 LAB MED JI Lab. Med. PD JUL PY 1994 VL 25 IS 7 BP 460 EP 463 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA NU189 UT WOS:A1994NU18900010 ER PT J AU PAIETTA, E ANDERSEN, J GALLAGHER, R BENNETT, J YUNIS, J CASSILETH, P ROWE, J WIERNIK, PH AF PAIETTA, E ANDERSEN, J GALLAGHER, R BENNETT, J YUNIS, J CASSILETH, P ROWE, J WIERNIK, PH TI THE IMMUNOPHENOTYPE OF ACUTE PROMYELOCYTIC LEUKEMIA (APL) - AN ECOG STUDY SO LEUKEMIA LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOCYTIC-LEUKEMIA; MONOCLONAL-ANTIBODIES; NEURAMINIDASE TREATMENT; CD2 EXPRESSION; CELLS; MARKER; ANTIGENS; GENE; CLASSIFICATION AB In 452 adult patients with de novo acute myeloid leukemia (AML), a series of 22 monoclonal antibodies was used to identify immunophenotypic characteristics of acute promyelocytic leukemia (APL) as compared to other AMLs (groups FAB M1/M2 and M4/M5). Only those patients with FAB M3 cytology were included in the analysis for which APL was confirmed by the presence of the t(15;17) cytogenetic aberration and the detection of the PML/RAR alpha gene fusion transcript by PCR amplification (35 cases). Significantly fewer APL blast cells were positive for the stem cell antigen, CD34 (p=0.0001) as well as for HLA-DR (p < 0.0001). With respect to myeloid antigens, APLs less frequently expressed the myelomonocytic antigens, CD11b (p=0.0001) and CD14 (p=0.0013), whereas expression of CD33, a pan-myeloid marker, was more frequent in APL (p=0.0001). CD15, the X-hapten carbohydrate structure (lacto-N-fucopentaose-III), typically expressed at the maturation stage of normal promyelocytes, was found to be sialylated on APL blasts as recognized by differential binding of the anti-CD15 antibodies, VIM-D5 (non-sialylated CD15) and VEP-9 (sialylated CD15). Expression of the T-cell associated CD7 antigen was rarer on APL than non-APL cells (p=0.0001), as was that of the multidrug resistance P-glycoprotein (p=0.0038). Marginal correlations existed between antigen profile (particularly CD2) and the type of PML/RAR alpha transcripts. In addition to its unique genotypic features, these data establish APL as a distinct immunophenotypic entity. C1 ALBERT EINSTEIN CANC CTR,BRONX,NY. UNIV ROCHESTER,DIV MED ONCOL,ROCHESTER,NY. THOMAS JEFFERSON UNIV,DIV CANC BIOL,PHILADELPHIA,PA. UNIV MIAMI,MIAMI,FL. EASTERN COOPERAT ONCOL GRP,DENVER,CO. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. RP PAIETTA, E (reprint author), MONTEFIORE MED CTR,DEPT ONCOL,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [NCI CA14958, NCI CA21115, NCI CA23318] NR 33 TC 101 Z9 103 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 1994 VL 8 IS 7 BP 1108 EP 1112 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA NZ723 UT WOS:A1994NZ72300003 PM 8035602 ER PT J AU WEDEEN, VJ WEISSKOFF, RM PONCELET, BP AF WEDEEN, VJ WEISSKOFF, RM PONCELET, BP TI MRI SIGNAL VOID DUE TO INPLANE MOTION IS ALL-OR-NONE SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note DE MR ARTIFACT; SIGNAL ATTENUATION; MOTION; SHEAR AB The process of MRI signal attenuation due to in-plane intravoxel velocity inhomogeneity is described. Given rigid rotation or linear shear, velocity phase-sensitivity will induce a phase distribution that varies linearly with position, which is exactly equivalent to the effect of a spatial phase encoding gradient pulse. It follows that the effect of such motion on the raw MRI signal is to displace it a fixed distance in k-space. Attenuation becomes marked when the center of the spin-echo reaches an edge of k-space, which happens when intravoxel phase shifts reach pi radian/voxel. Because spin echoes are typically peaked sharply at center, this attenuation usually is abrupt. Analytic and numerical simulations of linear and nonlinear velocity fields confirm abrupt MRI attenuation where phase dispersion exceeds pi radian/voxel. Examples of this phenomenon include the abrupt loss of blood signal adjacent the vessel wall in laminar flow, abrupt loss of subendocardial signal in early diastole, and sudden disappearance due to rotation of a kidney during a measurement of diffusion. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-39371] NR 9 TC 42 Z9 42 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUL PY 1994 VL 32 IS 1 BP 116 EP 120 DI 10.1002/mrm.1910320116 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NT738 UT WOS:A1994NT73800015 PM 8084226 ER PT J AU ZIETMAN, AL AF ZIETMAN, AL TI WHEN SHOULD RADIATION-THERAPY FOLLOW RADICAL PROSTATECTOMY IN THE MANAGEMENT OF PROSTATIC-CANCER SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID ADJUVANT RADIATION; CAPSULAR PENETRATION; ANTIGEN RP ZIETMAN, AL (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,GENITOURINARY ONCOL UNIT,100 BLOSSOM ST,BOSTON,MA 02114, USA. NR 9 TC 7 Z9 7 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JUL PY 1994 VL 69 IS 7 BP 700 EP 701 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NV257 UT WOS:A1994NV25700020 PM 7516989 ER PT J AU KARPERIEN, M VANDIJK, TB HOEIJMAKERS, T CREMERS, F ABOUSAMRA, AB BOONSTRA, J DELAAT, SW DEFIZE, LHK AF KARPERIEN, M VANDIJK, TB HOEIJMAKERS, T CREMERS, F ABOUSAMRA, AB BOONSTRA, J DELAAT, SW DEFIZE, LHK TI EXPRESSION PATTERN OF PARATHYROID-HORMONE PARATHYROID-HORMONE RELATED PEPTIDE RECEPTOR MESSENGER-RNA IN MOUSE POSTIMPLANTATION EMBRYOS INDICATES INVOLVEMENT IN MULTIPLE DEVELOPMENTAL PROCESSES SO MECHANISMS OF DEVELOPMENT LA English DT Article DE PARATHYROID HORMONE/PARATHYROID HORMONE RELATED PEPTIDE RECEPTOR; PARIETAL ENDODERM; IN SITU HYBRIDIZATION; ORGANOGENESIS; PARATHYROID HORMONE RELATED PEPTIDE ID ENDODERM DIFFERENTIATION; PARIETAL ENDODERM; MESSENGER-RNA; CARCINOMA-CELLS; CYCLIC-AMP; GROWTH; RAT; LOCALIZATION; TISSUES; GENE AB In this paper we describe the cloning of the mouse Parathyroid Hormone/Parathyroid Hormone related Peptide Receptor (PTH/PTHrPR) cDNA and expression of its mRNA during mouse postimplantation development from day 5.5 until day 15.5 post coitum (p.c.). In support of a model from previous studies, in which parietal endoderm differentiation is regulated by the interaction of the PTH/PTHrPR and Parathyroid Hormone related Peptide (PTHrP), high levels of PTH/PTHrPR mRNA levels were detected in developing parietal endoderm from day 5.5 p.c. and onwards. In the embryo proper, PTH/PTHrPR mRNA expression was mainly detected at sites of epithelium/mesenchyme interactions, starting at day 9.5 p.c. in the epithelium of the intestine and later in the mesenchyme of the lung, the epithelium of meso- and metanephric tubuli, the dermis and at all sites where bone formation takes place. The complexity of the PTH/PTHrPR expression pattern suggests tight developmental regulation and indicates multiple roles in embryogenesis for the receptor and its ligands, not only in extraembryonic tissue but also in the formation of various organs. C1 NETHERLANDS INST DEV BIOL,HUBRECHT LAB,3584 CT UTRECHT,NETHERLANDS. UNIV UTRECHT,DEPT MOLEC CELL BIOL,3584 CH UTRECHT,NETHERLANDS. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. NR 41 TC 64 Z9 65 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 JUL PY 1994 VL 47 IS 1 BP 29 EP 42 DI 10.1016/0925-4773(94)90093-0 PG 14 WC Developmental Biology SC Developmental Biology GA PF473 UT WOS:A1994PF47300003 PM 7524627 ER PT J AU GOLDBERG, HI CUMMINGS, MA STEINBERG, EP RICCI, EM SHANNON, T SOUMERAI, SB MITTMAN, BS EISENBERG, J HECK, DA KAPLAN, S KENZORA, JE VARGUS, AM MULLEY, AG RIMER, BK AF GOLDBERG, HI CUMMINGS, MA STEINBERG, EP RICCI, EM SHANNON, T SOUMERAI, SB MITTMAN, BS EISENBERG, J HECK, DA KAPLAN, S KENZORA, JE VARGUS, AM MULLEY, AG RIMER, BK TI DELIBERATIONS ON THE DISSEMINATION OF PORT PRODUCTS - TRANSLATING RESEARCH FINDINGS INTO IMPROVED PATIENT OUTCOMES SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the Association-for-Health-Services-Research CY JUN 30, 1991 CL SAN DIEGO, CA SP ASSOC HLTH SERV RES AB This report outlines the activities undertaken by the Inter-PORT Dissemination work group during its first 2 years of operation. The work group's initial purpose was to assist the individual PORTs in developing their plans for both disseminating research findings and evaluating the effectiveness of these strategies. However, it became quickly apparent that in a discipline little more than a decade old, a commonly understood vocabulary had yet to be adopted. Even the term ''dissemination'' held different meaning for different constituencies. Consequently, the work group has tried to encourage the development of both a definitional framework and a set of common data elements of importance to all dissemination programs. The work group has analogously attempted to agree on minimum standards of methodologic rigor as a starting point for coordination of evaluations across PORTs. To help determine the potential for further coordination, a matrix of each individual PORT's target audiences, intervention strategies, and evaluation designs has been constructed. Much remains to be learned before we can know with any certainty how best to translate research findings into useful behavior change and improved patient outcomes. Our goal is that the efforts of the work group will serve to catalyze this process. C1 UNIV WASHINGTON,SEATTLE,WA 98195. UNIV MARYLAND,BALTIMORE,MD 21201. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV PITTSBURGH,PITTSBURGH,PA 15260. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RAND CORP,SANTA MONICA,CA 90406. GEORGETOWN UNIV,WASHINGTON,DC 20057. INDIANA UNIV,MED CTR,BLOOMINGTON,IN 47401. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DUKE UNIV,DURHAM,NC 27706. AGCY HLTH CARE POLICY & RES,ROCKVILLE,MD. NR 5 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 1994 VL 32 IS 7 SU S BP JS90 EP JS110 DI 10.1097/00005650-199407001-00008 PG 21 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA NW560 UT WOS:A1994NW56000008 PM 8028416 ER PT J AU NATH, R BIGGS, PJ BOVA, FJ LING, CC PURDY, JA VANDEGEIJN, J WEINHOUS, MS AF NATH, R BIGGS, PJ BOVA, FJ LING, CC PURDY, JA VANDEGEIJN, J WEINHOUS, MS TI AAPM CODE OF PRACTICE FOR RADIOTHERAPY ACCELERATORS - REPORT OF AAPM RADIATION-THERAPY TASK GROUP NO-45 SO MEDICAL PHYSICS LA English DT Review ID ELECTRON ARC THERAPY; DYNAMIC STEREOTACTIC RADIOSURGERY; LINEAR-ACCELERATOR; X-RAYS; APPLICATOR SYSTEM; DOSIMETRIC PROPERTIES; DOSE DISTRIBUTIONS; FILM DOSIMETRY; OUTPUT FACTORS; PHOTON BEAMS C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT MED,BOSTON,MA 02114. UNIV FLORIDA,J HILLIS MILLER HLTH CTR,DEPT RADIAT THERAPY,GAINESVILLE,FL 32610. MEM SLOAN KETTERING CANC CTR,DEPT MED PHYS,NEW YORK,NY 10021. EDWARD MALLINCKRODT INST RADIOL,DIV RADIAT ONCOL,ST LOUIS,MO 63110. NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. RP NATH, R (reprint author), YALE UNIV,SCH MED,DEPT THERAPEUT RADIOL,NEW HAVEN,CT 06510, USA. NR 139 TC 103 Z9 104 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUL PY 1994 VL 21 IS 7 BP 1093 EP 1121 DI 10.1118/1.597398 PG 29 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NY972 UT WOS:A1994NY97200011 PM 7968843 ER PT J AU MIGUEL, EC PEREIRA, RMR PEREIRA, CAD BAER, L GOMES, RE DESA, LCF HIRSCH, R DEBARROS, NG DENAVARRO, JM GENTIL, V AF MIGUEL, EC PEREIRA, RMR PEREIRA, CAD BAER, L GOMES, RE DESA, LCF HIRSCH, R DEBARROS, NG DENAVARRO, JM GENTIL, V TI PSYCHIATRIC MANIFESTATIONS OF SYSTEMIC LUPUS-ERYTHEMATOSUS - CLINICAL-FEATURES, SYMPTOMS, AND SIGNS OF CENTRAL-NERVOUS-SYSTEM ACTIVITY IN 43 PATIENTS SO MEDICINE LA English DT Article ID CRANIAL COMPUTERIZED-TOMOGRAPHY; NEUROPSYCHIATRIC MANIFESTATIONS; BASAL GANGLIA; DISEASE; MIGRAINE; CRITERIA; CLASSIFICATION; DISTURBANCES; DISORDERS; DIAGNOSIS C1 UNIV SAO PAULO,SCH MED,DEPT PSYCHIAT,SAO PAULO,BRAZIL. UNIV SAO PAULO,SCH MED,DEPT RHEUMATOL,SAO PAULO,BRAZIL. UNIV SAO PAULO,SCH MED,DEPT RADIOL,SAO PAULO,BRAZIL. UNIV SAO PAULO,SCH MED,DEPT OPHTHALMOL,SAO PAULO,BRAZIL. UNIV SAO PAULO,SCH MED,DEPT NEUROL,SAO PAULO,BRAZIL. UNIV SAO PAULO,DEPT STAT,SAO PAULO,BRAZIL. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,CLIN RES & RES UNIT,BOSTON,MA. RI Miguel, Euripedes/B-2871-2008; Pereira, Rosa /C-5192-2012 NR 64 TC 48 Z9 51 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JUL PY 1994 VL 73 IS 4 BP 224 EP 232 DI 10.1097/00005792-199407000-00005 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA PA760 UT WOS:A1994PA76000005 PM 8041245 ER PT J AU LEE, I DEMHARTNER, TJ BOUCHER, Y JAIN, RK INTAGLIETTA, M AF LEE, I DEMHARTNER, TJ BOUCHER, Y JAIN, RK INTAGLIETTA, M TI EFFECT OF HEMODILUTION AND RESUSCITATION ON TUMOR INTERSTITIAL FLUID PRESSURE, BLOOD-FLOW, AND OXYGENATION SO MICROVASCULAR RESEARCH LA English DT Article ID SOLID TUMORS; SKELETAL-MUSCLE; HYPERTENSION; NICOTINAMIDE; HEMORRHAGE; RESISTANCE; HEMATOCRIT; TRANSPORT; MOLECULES; VOLUME AB Hemodilution due to hemorrhage may increase tumor blood flow (TBF) by lowering blood viscosity and decrease tumor interstitial fluid pressure (TIFP) by moving fluid from the interstitium to the vascular compartment and by lowering microvascular pressure (MVP), mainly due to the decrease in systemic pressure. To test this hypothesis, we measured mean arterial blood pressure (MABP), TIFP, hematocrit, relative TBF (RBC flux), and intratumor pO(2) during hemorrhage and volume restitution in severe combined immunodeficient mice, bearing LS174T human colon adenocarcinoma xenografts. MABP and TIFP significantly decreased after 0.2 mi of blood (similar to 12% of blood volume) was withdrawn. MABP decreased from 87.5 +/- 3.9 mmHg (mean +/- standard error) to 59.8+/-4.8 mmHg (n = 5, P = 0.01) within 2.5 min after the withdrawal of blood and then returned to control value within 10 min. TIFP gradually decreased from 18.7 +/- 2.3 mmHg to 11.3 +/- 0.9 mmHg after 1 hr (n = 8, P = 0.01), while RBC flux increased by a factor of 1.99 +/- 0.38 (n = 5, P = 0.02). The systemic hematocrit decreased from 51.2 to 45.9% (n = 7, P = 0.02). Tumor oxygenation did not significantly improve (median pO(2) for control, 28 mmHg, and median pO(2) after blood withdrawal, 32 mmHg; P = 0.14). When 0.2 mi blood was withdrawn and replaced (within 2.5 min) with the same volume of normal saline, MABP significantly decreased from 86.4 +/- 2.4 mmHg to 65.6 +/- 4.6 mmHg (n = 11) at 1 hr post-treatment (P = 0.001). TIFP decreased, but not significantly, from 24.2 +/- 2.9 mmHg to 20.4 +/- 2.4 mmHg (P = 0.35). Blood withdrawals in excess of 0.3 mi significantly decreased MABP and TIFP without recovery during 1 hr of observation. Volume restitution with hyperoncotic/hyperosmotic 6.0% Dextran 70 and 7.5% saline had effects attributable to a direct transmission of systemic pressure to the tumor microcirculation and to a lowering of tumor venous resistance. These effects appear to be common to saline blood restitution and volume top-load with Dextran 70. In conclusion, mild hemorrhage (withdrawal of similar to 12% of blood volume) can significantly lower TIFP without a reduction in TBF and pO(2). (C) 1994 Academic Press, Inc. C1 UNIV CALIF SAN DIEGO,DEPT APPL MECH & BIOENGN,SAN DIEGO,CA 92093. RP LEE, I (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-56591]; NHLBI NIH HHS [NHLBI HL-48018, NHLBI HL-17241] NR 43 TC 24 Z9 24 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD JUL PY 1994 VL 48 IS 1 BP 1 EP 12 DI 10.1006/mvre.1994.1034 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PA217 UT WOS:A1994PA21700001 PM 7990716 ER PT J AU QUELLE, FW SATO, N WITTHUHN, BS INHORN, RC EDER, M MIYAJIMA, A GRIFFIN, JD IHLE, JN AF QUELLE, FW SATO, N WITTHUHN, BS INHORN, RC EDER, M MIYAJIMA, A GRIFFIN, JD IHLE, JN TI JAK2 ASSOCIATES WITH THE BETA(C) CHAIN OF THE RECEPTOR FAR GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, AND ITS ACTIVATION REQUIRES THE MEMBRANE-PROXIMAL REGION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; GAMMA SIGNAL-TRANSDUCTION; GM-CSF RECEPTOR; ERYTHROPOIETIN RECEPTOR; INTERFERON-ALPHA/BETA; CYTOKINE RECEPTORS; MOLECULAR-CLONING; CELL-LINE; INTERLEUKIN-3; PHOSPHORYLATION AB The high-affinity receptor for granulocyte-macrophage colony-stimulating factor (GM-CSP) consists of a unique alpha chain and a beta(c) subunit that is shared with the receptors for interleukin-3 (IL-3) and IL-5. Two regions of the beta(c) chain have been defined; these include a membrane-proximal region of the cytoplasmic domain that is required for mitogenesis and a membrane-distal region that is required for activation of Ras, Raf-1, mitogen-activated protein kinase, and S6 kinase. Recent studies have implicated the cytoplasmic protein tyrosine kinase JAK2 in signalling through a number of the cytokine receptors, including the IL-3 and erythropoietin receptors. In the studies described here, we demonstrate that GM-CSF stimulation of cells induces the tyrosine phosphorylation of JAK2 and activates its in vitro kinase activity. Mutational analysis of the beta(c) chain demonstrates that only the membrane-proximal 62 amino acids of the cytosolic domain are required for JAK2 activation. Thus, JAK2 activation is correlated with induction of mitogenesis but does not, alone, activate the Ras pathway. Carboxyl truncations of the alpha chain which inactivate the receptor for mitogenesis, are unable to mediate GM-CSR-induced JAK2 activation. Using baculovirus-expressed proteins, we further demonstrate that JAK2 physically associated with the beta(c) chain but not with the alpha chain. Together, the results further support the hypothesis that the JAK family of kinases are critical to coupling cytokine binding to tyrosine phosphorylation and ultimately mitogenesis. C1 ST JUDE CHILDRENS RES HOSP, DEPT BIOCHEM, MEMPHIS, TN 38105 USA. UNIV TENNESSEE, SCH MED, HLTH SCI CTR, DEPT BIOCHEM, MEMPHIS, TN 38163 USA. DNAX RES INST MOLEC & CELLULAR BIOL INC, DEPT MOLEC BIOL, PALO ALTO, CA 94304 USA. DANA FARBER CANC INST, DIV TUMOR IMMUNOL, BOSTON, MA 02115 USA. FU NCI NIH HHS [R01 CA36167, P30 CA21765]; NIDDK NIH HHS [R01 DK42932] NR 39 TC 446 Z9 449 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1994 VL 14 IS 7 BP 4335 EP 4341 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT626 UT WOS:A1994NT62600001 PM 8007942 ER PT J AU CARTER, ME GULICK, T MOORE, DD KELLY, DP AF CARTER, ME GULICK, T MOORE, DD KELLY, DP TI A PLEIOTROPIC ELEMENT IN THE MEDIUM-CHAIN ACYL-COENZYME A DEHYDROGENASE GENE PROMOTER MEDIATES TRANSCRIPTIONAL REGULATION BY MULTIPLE NUCLEAR RECEPTOR TRANSCRIPTION FACTORS AND DEFINES NOVEL RECEPTOR-DNA BINDING MOTIFS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RETINOID-X-RECEPTOR; ACID RESPONSE PATHWAYS; A-I GENE; THYROID-HORMONE; ORPHAN RECEPTORS; COUP-TF; MOLECULAR-CLONING; ESCHERICHIA-COLI; DIRECT REPEAT; VITAMIN-D AB We previously identified a complex regulatory element in the medium-chain acyl coenzyme A dehydrogenase gene promoter that confers transcriptional regulation by the retinoid receptors RAR and RXR and the orphan nuclear receptor HNF-4. In this study we demonstrate a trans-repressing regulatory function for the orphan receptor COUP-TF at this same nuclear receptor response element (NRRE-1). The transcriptional regulatory properties and receptor binding sequences of each nuclear receptor response element within NRRE-1 are also characterized. NRRE-1 consists of four potential nuclear hormone receptor hexamer binding sites, arranged as [<--1-(n)(8)-2-->-3-->(n)(4)<--4-], three of which are used in alternative pairwise binding by COUP-TF and HNF-4 homodimers and by RAR-RXR heterodimers, as demonstrated by mobility shift assays and methylation interference analysis. Binding and transactivation studies with mutant NRRE-1 elements confirmed the existence of distinct retinoid, COUP-TF, and HNF-4 response elements that define novel receptor binding motifs: COUP-TF homodimers bound sites 1 and 3 (two hexamer repeat sequences arranged as an everted imperfect repeat separated by 14 bp or ER14), RAR-RXR heterodimers bound sites 1 and 2 (ER8), and HNF-4 homodimers bound sites 2 and 3 (imperfect DRO). Mixing cotransfection experiments demonstrated that the nuclear receptor dimers compete at NRRE-1 to modulate constitutive and ligand-mediated transcriptional activity. These data suggest a mechanism for the transcriptional modulation of genes encoding enzymes involved in cellular metabolism. C1 WASHINGTON UNIV,SCH MED,DEPT MED,DIV CARDIOVASC,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MOLEC BIOL & PHARMACOL,ST LOUIS,MO 63110. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. FU NIDDK NIH HHS [DK45416] NR 63 TC 87 Z9 88 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1994 VL 14 IS 7 BP 4360 EP 4372 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT626 UT WOS:A1994NT62600004 PM 8007945 ER PT J AU CHEATHAM, B VLAHOS, CJ CHEATHAM, L WANG, L BLENIS, J KAHN, CR AF CHEATHAM, B VLAHOS, CJ CHEATHAM, L WANG, L BLENIS, J KAHN, CR TI PHOSPHATIDYLINOSITOL 3-KINASE ACTIVATION IS REQUIRED FOR INSULIN STIMULATION OF PP70 S6 KINASE, DNA-SYNTHESIS, AND GLUCOSE-TRANSPORTER TRANSLOCATION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR STIMULATION; FACTOR-I RECEPTOR; MIDDLE T-ANTIGEN; INTACT-CELLS; PI 3-KINASE; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; STRUCTURAL FEATURES; 3T3-L1 ADIPOCYTES; PROTEIN-KINASE AB Phosphatidylinositol 3-kinase (PI 3-kinase) is stimulated by insulin and a variety of growth factors, but its exact role in signal transduction remains unclear. We have used a novel, highly specific inhibitor of PI 3-kinase to dissect the role of this enzyme in insulin action. Treatment of intact 3T3-L1 adipocytes with LY294002 produced a dose-dependent inhibition of insulin-stimulated Pi 3-kinase (50% inhibitory concentration, 6 PM) with > 95% reduction in the levels of phosphatidylinositol3,4,5-trisphosphate without changes in the levels of phosphatidylinositol-4-monophosphate or its derivatives. In parallel, there was a complete inhibition of insulin-stimulated phosphorylation and activation of pp70 S6 kinase. Inhibition of PI 3-kinase also effectively blocked insulin- and serum-stimulated DNA synthesis and insulin-stimulated glucose uptake by inhibiting translocation of GLUT 4 glucose transporters to the plasma membrane. By contrast, LY294002 had no effect on insulin stimulation of mitogen-activated protein kinase or pp90 S6 kinase. Thus, activation of PI 3-kinase plays a critical role in mammalian cells and is required for activation of pp70 S6 kinase and DNA synthesis and certain forms of intracellular vesicular trafficking but not mitogen-activated protein kinase or pp90 S6 kinase activation. These data suggest that PI 3-kinase is not only an important component but also a point of divergence in the insulin signaling network. C1 HARVARD UNIV, BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR, DEPT MED,DIV RES, BOSTON, MA 02215 USA. ELI LILLY & CO, LILLY RES LABS, CARDIOVASC RES, INDIANAPOLIS, IN 46285 USA. HARVARD UNIV, SCH MED, DEPT CELL & MOLEC PHYSIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, PROGRAM CELL & DEV BIOL, BOSTON, MA 02115 USA. RI Cheatham, Lynn/I-7649-2014 FU NCI NIH HHS [CA 46595]; NIDDK NIH HHS [DK 31036, DK 33201] NR 59 TC 999 Z9 1005 U1 3 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1994 VL 14 IS 7 BP 4902 EP 4911 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT626 UT WOS:A1994NT62600059 PM 8007986 ER PT J AU HAO, EH MENKE, JB SMITH, AM JONES, C GEFFNER, ME HERSHMAN, JM WUERTH, JP SAMUELS, HH WAYS, DK USALA, SJ AF HAO, EH MENKE, JB SMITH, AM JONES, C GEFFNER, ME HERSHMAN, JM WUERTH, JP SAMUELS, HH WAYS, DK USALA, SJ TI DIVERGENT DIMERIZATION PROPERTIES OF MUTANT BETA-1 THYROID-HORMONE RECEPTORS ARE ASSOCIATED WITH DIFFERENT DOMINANT-NEGATIVE ACTIVITIES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RETINOIC ACID RECEPTORS; LIGAND-BINDING DOMAIN; GENERALIZED RESISTANCE; RESPONSE ELEMENTS; X-RECEPTOR; HISTIDINE MUTATION; AUXILIARY PROTEIN; ENHANCES BINDING; GENE; DNA AB Syndromes of resistance to thyroid hormones are caused by mutations in the T-3-binding domain of the c-erbA beta thyroid hormone receptor gene. The S receptor (deletion of THR332) is a potent dominant negative protein cloned from a kindred with generalized resistance to thyroid hormones. The G-H receptor (ARG311HIS) has compromised dominant negative function and was found in both normal individuals and in a patient with severe pituitary resistance to thyroid hormones. We have investigated the mechanism responsible for the difference in receptor phenotypes by analyzing the binding of S and G-H receptors to thyroid hormone response elements with electrophoretic mobility shift analysis. Wild-type human c-erbA beta 1 (WT), S, and G-H receptors were synthesized in reticulocyte lysate, reacted with a thyroid hormone response element consisting of a direct repeat with 4 base pairs (DR+4; AGGTCA CAGG AGGTCA), and the products analyzed by gel shift. G-H receptor homodimerization was greatly impaired; G-H formed predominantly monomeric complex compared with monomeric and homodimeric WT complexes. The G-H receptor was able to form heterodimeric complexes with cellular thyroid hormone receptor auxiliary protein (TRAP) factors including the human retinoid X receptor-alpha. When TRAP was limiting, the levels of G-H heterodimeric complex were 2- to 3-fold reduced compared with Wi receptor. In contrast to the WT and G-H receptors, the S receptor formed almost exclusively homodimeric complex with DR+4; the approximate ratio of S:WT:G-H homodimeric complexes at equivalent concentrations of receptors was 60:20:1. A measurable increase (1.2- to 2.6-fold) in heterodimeric complex formation was observed with the S receptor relative to WT when TRAP was at limiting concentration. As reported previously by others, thyroid hormone significantly reduced the WT homodimeric complex with DR+4. There was no effect on the S homodimeric complex. Finally, the WT, S, and G-H receptors formed different complexes with the element consisting of an inverted repeat with 5 base pairs (IR+5; AGGTCA ACAGT TGACCT) and the IR element (AGGTCA TGACCT), which were differently regulated by thyroid hormone. The S receptor bound as a homodimer with IR+5, whereas the WT receptor bound as a homodimer only with thyroid hormone. No homodimeric complex formed with IR+5 and the G-H receptor. Qualitatively similar results were observed with the IR element. We conclude that the ARG311HIS mutation severely perturbs the homodimerization and, to a much less degree, heterodimerization functions of the c-erbAB1 receptor. Furthermore, the THR332 deletion mutation augments homodimerization of the c-erbA81 receptor. These results indicate that different mutations in the c-erbAB1 thyroid hormone receptor have divergently affected dimerization activities which seem to influence the level of dominant negative activity in man. C1 E CAROLINA UNIV, SCH MED, DEPT MED, ENDOCRINOL SECT, GREENVILLE, NC 27858 USA. E CAROLINA UNIV, SCH MED, DEPT MICROBIOL & IMMUNOL, GREENVILLE, NC 27858 USA. UNIV CALIF LOS ANGELES, MED CTR, DEPT PEDIAT, LOS ANGELES, CA 90024 USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT MED, LOS ANGELES, CA 90073 USA. NYU, MED CTR, DEPT MED, NEW YORK, NY 10016 USA. NYU, MED CTR, DEPT MED, DIV MOLEC ENDOCRINOL, NEW YORK, NY 10016 USA. NYU, MED CTR, DEPT PHARMACOL, NEW YORK, NY 10016 USA. FU NCI NIH HHS [CA-43823]; NIDDK NIH HHS [DK-42807, DK-16636] NR 50 TC 35 Z9 35 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1994 VL 8 IS 7 BP 841 EP 851 DI 10.1210/me.8.7.841 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NY971 UT WOS:A1994NY97100003 PM 7984146 ER PT J AU KHARBANDA, S EMOTO, Y KISAKI, H SALEEM, A KUFE, D AF KHARBANDA, S EMOTO, Y KISAKI, H SALEEM, A KUFE, D TI L-BETA-D-ARABINOFURANOSYLCYTOSINE ACTIVATES SERINE/THREONINE PROTEIN-KINASES AND C-JUN GENE-EXPRESSION IN PHORBOL ESTER-RESISTANT MYELOID-LEUKEMIA CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID DNA-SYNTHESIS; 1-BETA-D-ARABINOFURANOSYLCYTOSINE INCORPORATION; TRANSCRIPTIONAL REGULATION; PHOSPHORYLATION; DIFFERENTIATION; DOMAIN; ONCOGENE; BINDING; AP-1; STAUROSPORINE AB 1-beta-D-Arabinofuranosylcytosine (ara-C) is an effective antileukemic agent that misincorporates into DNA. Recent studies have demonstrated that ara-C treatment is associated with transient induction of the c-jun early response gene. The present studies have examined the effects of ara-C on c-jun expression in a phorbol ester-resistant variant of the HL-60 myeloid leukemia cell line, designated HL-525, that is deficient in protein kinase C (PKC)-mediated signal transduction and fails to respond to 12-O-tetradecanoylphorbol-13-acetate with induction of c-jun transcripts. The results demonstrate that treatment of HL-525 cells with ara-C is associated with transcriptional activation of the c-jun gene. We also demonstrate that ara-C treatment is associated with activation of a PKC-like activity. Partial purification of this Ca2+-independent activity has demonstrated phosphorylation of synthetic peptides derived from (a) amino acids 4-14 of myelin basic protein and (b) the pseudosubstrate region of PKC (amino acids 19-31), with substitution of Ala(25) with serine. The finding that the ara-C-induced activity is inhibited by the pseudosubstrate PKC(19-36) supports the activation of a PKC-like enzyme. Because PKC can act upstream of the mitogen-activated protein (MAP) kinases, we studied the effects of ara-C treatment on MAP kinase activity. The results demonstrate that MAP kinase is activated in ara-C-treated cells and that the kinetics of this activation are similar to those of the PKC-like activity. Because 12-O-tetradecanoylphorbol-13-acetate has little, if any, effect on the PKC-like and MAP kinase activities in HL-525 cells, these findings suggest that ara-C activates a distinct signaling cascade that may contribute to induction of the c-jun gene. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. FU NCI NIH HHS [CA29431, CA42802] NR 50 TC 23 Z9 25 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 JUL PY 1994 VL 46 IS 1 BP 67 EP 72 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NZ052 UT WOS:A1994NZ05200009 PM 8058058 ER PT J AU HUBERT, R MACDONALD, M GUSELLA, J ARNHEIM, N AF HUBERT, R MACDONALD, M GUSELLA, J ARNHEIM, N TI HIGH-RESOLUTION LOCALIZATION OF RECOMBINATION HOT-SPOTS USING SPERM TYPING SO NATURE GENETICS LA English DT Article ID POLYMERASE CHAIN-REACTION; HUNTINGTONS-DISEASE GENE; PHYSICAL MAP; HUMAN GENOME; LINKAGE MAP; SHORT ARM; REGION; AMPLIFICATION; POLYMORPHISMS; CHROMOSOMES AB We have applied sperm DNA typing to determine the distribution of crossover events within a one megabase region of the short arm of human chromosome 4 near the locus for Huntington disease. A total of 29 recombinants were detected among 602 sperm typed after whole genome amplification. These recombinants were typed for seven polymorphic markers. The 280 kilobase D4S10-D4S126 interval was found to undergo recombination at a 6-9-fold greater rate per unit of physical distance than the adjacent 720 kb D4S126-D4S127 interval. Sperm typing has the potential to dissect mammalian recombination hot spots to the point where DNA sequence analysis may reveal the molecular basis for hyperrecombination. C1 UNIV SO CALIF,PROGRAM MOLEC BIOL,LOS ANGELES,CA 90089. MASSACHUSETTS GEN HOSP,NEUROGENET PROGRAM,BOSTON,MA 02114. NR 32 TC 61 Z9 62 U1 0 U2 1 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 JUL PY 1994 VL 7 IS 3 BP 420 EP 424 DI 10.1038/ng0794-420 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA NU306 UT WOS:A1994NU30600018 PM 7920662 ER PT J AU JACOBS, D SANO, M MARDER, K BELL, K BYLSMA, F LAFLECHE, G ALBERT, M BRANDT, J STERN, Y AF JACOBS, D SANO, M MARDER, K BELL, K BYLSMA, F LAFLECHE, G ALBERT, M BRANDT, J STERN, Y TI AGE AT ONSET OF ALZHEIMERS-DISEASE - RELATION TO PATTERN OF COGNITIVE DYSFUNCTION AND RATE OF DECLINE SO NEUROLOGY LA English DT Article ID MINI-MENTAL STATE; LANGUAGE DYSFUNCTION; DEMENTIA; PROGRESSION; PREDICTORS; IMPAIRMENT; PRESENILE; FEATURES AB We examined the pattern of cognitive impairment and rate of cognitive and functional decline as a function of age at symptom onset in 127 patients with probable Alzheimer's disease (AD). At baseline, early-onset (before age 65) and late-onset groups were mildly and comparably impaired on the modified Mini-Mental State Examination (mMMS) and the Blessed Dementia Rating Scale-Part 1 (BDRS). Repeated-measures analysis of variance revealed significantly more rapid decline in early-onset subjects over a 2-year follow-up period. Multivariate linear regression analyses indicated that age at symptom onset strongly predicted rate of decline on the mMMS and the BDRS, even after controlling for symptom duration, gender, family history of dementia, and baseline mMMS and BDRS scores. Early- and late-onset AD subjects also differed in terms of pattern of performance on the mMMS. Early-onset subjects scored significantly lower than late-onset subjects on attentional items of the mMMS at baseline and follow-up. Conversely, late-onset subjects scored significantly lower than early-onset subjects on memory and naming items at baseline, and the two groups were comparable on these tasks at follow-up. Results provide longitudinal evidence of more rapid cognitive and functional decline in subjects with early-onset AD and suggest that early-onset AD may be characterized by predominant impairment of attentional skills. C1 COLUMBIA UNIV,COLL PHYSICIANS & SURGEONS,DEPT NEUROL,NEW YORK,NY. COLUMBIA UNIV,COLL PHYSICIANS & SURGEONS,DEPT PSYCHIAT,NEW YORK,NY. JOHNS HOPKINS UNIV,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,BOSTON,MA. RP JACOBS, D (reprint author), COLUMBIA UNIV,COLL PHYSICIANS & SURGEONS,GERTRUDE H SERGIEVSKY CTR,630 W 168TH ST,NEW YORK,NY 10032, USA. OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG07370, AG08702] NR 32 TC 170 Z9 171 U1 4 U2 10 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL PY 1994 VL 44 IS 7 BP 1215 EP 1220 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA NX632 UT WOS:A1994NX63200005 PM 8035918 ER PT J AU LIPTON, SA AF LIPTON, SA TI HIV COAT PROTEIN GP120 INDUCES SOLUBLE NEUROTOXINS IN CULTURE-MEDIUM SO NEUROSCIENCE RESEARCH COMMUNICATIONS LA English DT Article DE AIDS; HIV-1; GP120; NMDA RECEPTOR; GLUTAMATE NEUROTOXICITY; RETINAL GANGLION CELLS ID NEURONAL INJURY; ENVELOPE PROTEIN; CEREBROSPINAL-FLUID; NMDA RECEPTOR; GLYCOPROTEIN; MACROPHAGES; METABOLITES; INFECTION; PEPTIDE; ACID AB Incubation in picomolar concentrations of HIV envelope protein gp120 induces neuronal injury in mixed neuronal-glial cultures. A polyclonal antiserum specific for gp120 abrogates these lethal effects. Conditioned medium harvested from cultures incubated overnight in gp120 also produces neurotoxicity. However, the addition of anti-gp120 antiserum to the conditioned medium only partially ameliorates its deleterious effects on neurons. These results suggest that neurotoxic substances are released in response to incubation of cultures in gp120, and these toxins accumulate in the conditioned medium. Taken together with previous findings that monocytic and astrocytic glial cells are necessary for the full expression of gp120-induced neuronal injury, the new data are consistent with the notion that gp120 stimulates glial cells to release these neurotoxic factors. Alternatively, the induction of an autotoxic substance by neurons via an interaction with glial cells is possible. C1 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,PROGRAM NEUROSCI,BOSTON,MA. RP LIPTON, SA (reprint author), CHILDRENS HOSP,DEPT NEUROL,CELLULAR & MOLEC NEUROSCI LAB,300 LONGWOOD AVE,BOSTON,MA 02115, USA. NR 23 TC 21 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0893-6609 J9 NEUROSCI RES COMMUN JI Neurosci. Res. Commun. PD JUL-AUG PY 1994 VL 15 IS 1 BP 31 EP 37 PG 7 WC Neurosciences SC Neurosciences & Neurology GA PA792 UT WOS:A1994PA79200004 ER PT J AU DELACUESTA, RS GOFF, BA FULLER, AF NIKRUI, N EICHHORN, JH RICE, LW AF DELACUESTA, RS GOFF, BA FULLER, AF NIKRUI, N EICHHORN, JH RICE, LW TI PROGNOSTIC IMPORTANCE OF INTRAOPERATIVE RUPTURE OF MALIGNANT OVARIAN EPITHELIAL NEOPLASMS SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID STAGE-I; CANCER; CARCINOMA; SURVIVAL; CHEMOTHERAPY; THERAPY; GRADE; CISPLATIN; TUMORS AB Objective: To determine whether rupture of malignant ovarian epithelial tumors at the time of operation influences the patient's overall prognosis. Methods: Between 1975 and 1990, 79 patients with stage I invasive epithelial ovarian cancer were treated at Massachusetts General Hospital. Patients were identified from the tumor registry, and charts were reviewed retrospectively. In 71 of the 79 cases, pathologic slides were evaluated. Of the 79 patients, 36 had stage Ia tumors, 20 stage Ic secondary to intraoperative rupture (Ic-rupture), and 17 stage Ic secondary to capsular invasion-serosal disease or positive ascites or washings (stage Ic-other). Survival analysis was performed to compare the three groups of patients. Results: There were four recurrences and deaths among the 20 women with stage Ic-rupture tumors (20%), compared to one (3%) among the 36 women with stage Ia. The recurrence-free survival at the median follow-up time for the two groups was 97 +/- 3 and 78 +/- 10 months, respectively (P = .03); overall survival was 97 +/- 3 and 73 +/- 12 months (P = .04). There were two recurrences (12%) and one death (6%) among the 17 women with stage Ic-other, giving recurrence-free and overall survivals of 88 +/- 8 and 94 +/- 6 months, respectively. The survival experience of this last group was not significantly different from that in the Ic-rupture group (P =.2). The hazard ratios for overall survival associated with stage Ic-rupture and each potential confounder, except for bloating, exceeded 6.5, with P less than or equal to.10. All deaths occurred in the 28 patients with grade 2 or 3 tumors. Even in this smaller group, the hazard ratio for stage Ic-rupture was 6.8 (P =.09). Conclusion: Intraoperative rupture of malignant epithelial ovarian neoplasms may worsen the prognosis of patients with stage I ovarian canter. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. RP DELACUESTA, RS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VINCENT MEM GYNECOL ONCOL SERV,VINCENT 1,FRUIT ST,BOSTON,MA 02114, USA. NR 45 TC 89 Z9 89 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 1994 VL 84 IS 1 BP 1 EP 7 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PH953 UT WOS:A1994PH95300001 ER PT J AU WERTHEIM, I FLEISCHHACKER, D MCLACHLIN, CM RICE, LW BERKOWITZ, RS GOFF, BA AF WERTHEIM, I FLEISCHHACKER, D MCLACHLIN, CM RICE, LW BERKOWITZ, RS GOFF, BA TI PSEUDOMYXOMA PERITONEI - A REVIEW OF 23 CASES SO OBSTETRICS AND GYNECOLOGY LA English DT Review ID MUCINOUS TUMORS; BORDERLINE MALIGNANCY; OVARY; APPENDIX; ORIGIN; FEATURES AB Objective: To review the experience at the Massachusetts General and Brigham and Women's Hospitals with 23 women treated for pseudomyxoma peritonei between 1961 and 1991. Methods: Patients were identified retrospectively from the tumor registry at the Massachusetts General and Brigham and Women's Hospitals, and all charts were reviewed. The median follow-up interval was 2.5 years (range 3 months to 31 years). Results: The mean age at diagnosis was 58 years (range 26-76). Pseudomyxoma peritonei was found in association with ten (44%) ovarian tumors of borderline malignancy, nine (39%) ovarian cystadenocarcinomas, and four (17%) appendiceal cystadenocarcinomas. Three patients had synchronous tumors in the ovary and appendix. All patients underwent surgical staging and cytoreduction. Eleven patients received postoperative therapy and, of these, nine developed a recurrence; 12 patients received no further therapy and, of these, three developed a recurrence. However, these groups were not pathologically comparable. With respect to survival, of the ten patients with borderline malignancies, seven had no evidence of disease, one was alive with disease, and two died of disease. For the nine patients with ovarian cystadenocarcinomas, three had no evidence of disease, one was alive with disease, and five died of disease (median time to death 18 months). For the four patients with appendiceal carcinomas, two had no disease, one was alive with disease, and one died with disease. Among all 23 patients, 12 (52%) developed a recurrence, with a range of time to first recurrence of 3 months to 19 years. Eight women required at least one additional laparotomy because of accumulation of gelatinous material. Conclusions: Although pseudomyxoma peritonei is associated with borderline and well-differentiated tumors, recurrence is common and the prognosis after recurrence is guarded. Involvement of the appendix is common; therefore, appendectomy is indicated when pseudomyxoma is encountered. To date, surgery has been the only effective therapy for this disease, and adjuvant therapy has not been shown conclusively to be of benefit. C1 MASSACHUSETTS GEN HOSP,VINCENT MEM GYNECOL ONCOL SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV WOMENS & PERINATAL PATHOL,BOSTON,MA 02115. RP WERTHEIM, I (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GYNECOL ONCOL,333 LONGWOOD AVE,SUITE 520,BOSTON,MA 02115, USA. NR 25 TC 46 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 1994 VL 84 IS 1 BP 17 EP 21 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PH953 UT WOS:A1994PH95300004 PM 8008316 ER PT J AU RODRIGUEZ, A AKOVA, YA PEDROZASERES, M FOSTER, CS AF RODRIGUEZ, A AKOVA, YA PEDROZASERES, M FOSTER, CS TI POSTERIOR SEGMENT OCULAR MANIFESTATIONS IN PATIENTS WITH HLA-B27-ASSOCIATED UVEITIS SO OPHTHALMOLOGY LA English DT Article ID ACUTE ANTERIOR UVEITIS; JUVENILE RHEUMATOID-ARTHRITIS; HL-A 27; CROHNS-DISEASE; ANKYLOSING-SPONDYLITIS; RETINAL VASCULITIS; CLINICAL-FEATURES; HLA-B27; COMPLICATIONS AB Purpose: To describe a series of patients with seronegative arthritic syndromes and HLA-B27-associated uveitis with severe, sight-threatening, posterior segment ocular manifestations. Methods: The authors reviewed the records of 29 patients (17.4%) with posterior segment involvement from a cohort of 166 patients with HLA-B27-associated uveitis. The inclusion criteria included individuals with a positive HLA-B27 who had at least one of the following findings: (1) severe vitreous inflammation; (2) papillitis; (3) retinal vasculopathy; or (4) pars plana exudates. The study population comprised 13 men and 16 women with a mean age at onset of uveitis of 35.2 years. The average duration of the uveitis was 5.3 years, and the median follow-up time was 26 months. Findings: Posterior segment involvement occurred in 34 eyes of the 29 patients. The most common findings included severe and diffuse vitritis in 93.1% of the patients and papillitis in 24 patients (82.7%). Retinal vasculitis occurred in seven patients (24.1%), and pars plana exudates were present in two patients (6.8%). Cystoid macular edema (37.9%) and epiretinal membrane (17.2%) were common causes of visual impairment. Systemic immunosuppressive therapy was required for control of inflammation in 32% of the patients. Conclusion: HLA-B27-associated uveitis may be related to severe, sight-threatening posterior segment manifestations in some patients; this is an under-recognized phenomenon. These patients may require the use of aggressive systemic immunosuppressive therapy to control inflammation and preserve vision. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. NR 35 TC 52 Z9 60 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUL PY 1994 VL 101 IS 7 BP 1267 EP 1274 PG 8 WC Ophthalmology SC Ophthalmology GA NY941 UT WOS:A1994NY94100026 PM 8035991 ER PT J AU DELAMAZA, MS FOSTER, CS JABBUR, NS AF DELAMAZA, MS FOSTER, CS JABBUR, NS TI SCLERITIS ASSOCIATED WITH RHEUMATOID-ARTHRITIS AND WITH OTHER SYSTEMIC IMMUNE-MEDIATED DISEASES SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT American-Academy-of-Ophthalmology Annual Meeting CY NOV, 1993 CL CHICAGO, IL SP AMER ACAD OPHTHALMOL ID EPISCLERITIS AB Purpose: Rheumatoid arthritis is the most common systemic immune-mediated condition associated with scleritis. The purpose of this study is to determine whether or not scleritis is more severe in patients with rheumatoid arthritis than in those without associated disease (''idiopathic scleritis''), or than in patients with other systemic immune-mediated diseases. Methods: Patient characteristics, type of scleritis, and ocular complications of 32 patients with scleritis associated with rheumatoid arthritis were compared with those of 74 patients with idiopathic scleritis and with those of 50 patients with scleritis associated with other systemic immune-mediated diseases. Results: Patients with scleritis associated with rheumatoid arthritis were older (mean age, 60.78; P = 0.0011) and more often had necrotizing scleritis (34%; P = 0.0001), decrease in vision (59%; P = 0.0001), and peripheral ulcerative keratitis (31%; P = 0.0001) than patients with idiopathic scleritis; by contrast, there was no statistical association with sex, bilaterality, anterior uveitis, glaucoma, or cataract. Patients with scleritis associated with rheumatoid arthritis were older (P = 0.0261) and more often had bilateral scleritis (53%; P = 0.0221) than patients with scleritis associated with other systemic immune-mediated diseases; however, there was no statistical association with type of scleritis, sex, decrease in vision, anterior uveitis, peripheral ulcerative keratitis, glaucoma, or cataract. Conclusions: Scleritis associated with rheumatoid arthritis is more severe than idiopathic scleritis but is as severe as scleritis associated with other immune-mediated diseases. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,OCULAR IMMUNOL SERV,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLS IMMUNOL LAB,BOSTON,MA. NR 28 TC 36 Z9 37 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 JUL PY 1994 VL 101 IS 7 BP 1281 EP 1286 PG 6 WC Ophthalmology SC Ophthalmology GA NY941 UT WOS:A1994NY94100028 PM 8035992 ER PT J AU LOSTY, PD PACHECO, BA MANGANARO, TF DONAHOE, PK JONES, RC SCHNITZER, JJ AF LOSTY, PD PACHECO, BA MANGANARO, TF DONAHOE, PK JONES, RC SCHNITZER, JJ TI PRENATAL HORMONAL-THERAPY IMPROVES PULMONARY MORPHOLOGY IN RATS WITH NITROFEN-INDUCED CONGENITAL DIAPHRAGMATIC-HERNIA SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PEDIAT SURG RES LABS,BOSTON,MA. NR 0 TC 2 Z9 2 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 JUL PY 1994 VL 36 IS 1 BP A25 EP A25 DI 10.1203/00006450-199407000-00135 PN 2 PG 1 WC Pediatrics SC Pediatrics GA NU474 UT WOS:A1994NU47400135 ER PT J AU CARROLL, M MATHEYPREVOT, B DANDREA, A AF CARROLL, M MATHEYPREVOT, B DANDREA, A TI DIFFERENTIATION DOMAINS OF THE ERYTHROPOIETIN RECEPTOR SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Workshop on the Superfamily of Receptors for Growth Hormone, Prolactin, Erythropoietin, and Cytokines CY NOV 07-11, 1993 CL HAIFA, ISRAEL SP GROWTH & GROWTH HORMONE FORUM ID CYTOKINE RECEPTORS; CYTOPLASMIC DOMAIN; ACTIVATION; SIGNALS; CELLS AB Ectopic expression of the erythropoietin receptor (Epo-R) in Ba/F3, an interleukin-3 (IL-3)-dependent progenitor cell line, confers both Epo-dependent cell growth and Epo-dependent induction of beta-globin mRNA. We have used this system of limited erythroid differentiation to characterize the role of the Epo-R in differentiation. In particular, we have been interested in identifying a differentiation domain of the Epo-R. We have studied three chimeras encoding regions of the extracellular region of the Epo-R and the intracellular region of the IL-3R beta(IL3). After transfection into Ba/F3 cells, all three chimeras conferred Epo-dependent growth and induced the expression of P-globin, suggesting that the extracellular region of the Epo-R plays a critical role in differentiation. However, a truncated Epo-R containing only the extracellular region of the Epo-R and a 35 amino acid cytoplasmic tail does not induce beta-globin expression, although it is processed to the cell surface and binds Epo. These experiments show that the extracytoplasmic region of the Epo-R is necessary but not sufficient to induce erythroid-specific differentiation in this system. RP CARROLL, M (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [5PO1 HL32262] NR 11 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD JUL PY 1994 VL 206 IS 3 BP 289 EP 294 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PE178 UT WOS:A1994PE17800025 PM 8016166 ER PT J AU PARDEE, AB AF PARDEE, AB TI PROTEINS IN 5 DIMENSIONS SO PROTEIN SCIENCE LA English DT Editorial Material ID CYCLIN RP PARDEE, AB (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 11 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 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JUL PY 1994 VL 3 IS 7 BP 1136 EP 1139 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NU550 UT WOS:A1994NU55000021 PM 7920264 ER PT J AU BROWNBEASLEY, MW AF BROWNBEASLEY, MW TI PROPOSAL FOR A NATIONAL PSYCHIATRIC INFORMATICS SYSTEM (NPIS) SO PSYCHIATRIC ANNALS LA English DT Article C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUL PY 1994 VL 24 IS 7 BP 357 EP 361 PG 5 WC Psychiatry SC Psychiatry GA NX262 UT WOS:A1994NX26200006 ER PT J AU BIEDERMAN, J FARAONE, SV SPENCER, T WILENS, T MICK, E LAPEY, KA AF BIEDERMAN, J FARAONE, SV SPENCER, T WILENS, T MICK, E LAPEY, KA TI GENDER DIFFERENCES IN A SAMPLE OF ADULTS WITH ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO PSYCHIATRY RESEARCH LA English DT Article DE ADULT ATTENTION DEFICIT HYPERACTIVITY DISORDER; GENDER; DIAGNOSIS ID MINIMAL BRAIN-DYSFUNCTION; PSYCHIATRIC STATUS; FOLLOW-UP; LEARNING-DISABILITIES; RISK-FACTORS; CHILDREN; FAMILY; COMORBIDITY; BOYS; METHYLPHENIDATE AB Although originally conceptualized as a childhood disorder, attention deficit hyperactivity disorder (ADHD) may also be an adult disorder. However, despite increasing media attention to adult ADHD, its validity has only recently been studied in a systematic fashion. The overrepresentation of females in adult samples in comparison to pediatric samples of ADHD raises additional questions about the validity of this disorder in adults. The goal of this article is to explore whether ADHD is a valid clinical entity in female subjects and whether it is expressed differently in male and female adults. To this end, we examined the clinical, cognitive, and functional characteristics of 128 referred adult ADHD cases of both sexes. Each subject had a clinical diagnosis of childhood-onset ADHD confirmed by structured interview. The male and female ADHD adults were similar to one another but more disturbed and impaired than non-ADHD adult control subjects. Compared with normal control females, ADHD women had higher rates of major depression, anxiety disorders, and conduct disorder; and more evidence of school failure and cognitive impairment. The consistency of these findings in both genders further supports the validity of the diagnosis of ADHD in adults. Our results stress the viability and importance of identification of female subjects with ADHD. The underidentification and undertreatment of females with ADHD may have substantial mental health and educational implications, suggesting that research is needed to develop a better understanding of clinical indicators of ADHD in females. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. VET ADM MED CTR,SOCIAL & COMMUNITY PSYCHIAT UNIT,BROCKTON,MA. RP BIEDERMAN, J (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,FRUIT ST,BOSTON,MA 02114, USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-41314-01A2] NR 48 TC 167 Z9 170 U1 2 U2 9 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 JUL PY 1994 VL 53 IS 1 BP 13 EP 29 DI 10.1016/0165-1781(94)90092-2 PG 17 WC Psychiatry SC Psychiatry GA PE502 UT WOS:A1994PE50200002 PM 7991729 ER PT J AU GREENBERG, DB AF GREENBERG, DB TI SYMPTOMS OF SCHIZOPHRENIA - COSTELLO,CG SO PSYCHOSOMATICS LA English DT Book Review C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP GREENBERG, DB (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JUL-AUG PY 1994 VL 35 IS 4 BP 408 EP 409 PG 2 WC Psychiatry; Psychology SC Psychiatry; Psychology GA NU448 UT WOS:A1994NU44800013 ER PT J AU HELD, KD BIAGLOW, JE AF HELD, KD BIAGLOW, JE TI MECHANISMS FOR THE OXYGEN RADICAL-MEDIATED TOXICITY OF VARIOUS THIOL-CONTAINING COMPOUNDS IN CULTURED-MAMMALIAN-CELLS SO RADIATION RESEARCH LA English DT Article ID CONTAINING RADIOPROTECTOR DITHIOTHREITOL; N-ACETYLCYSTEINE; CYSTEAMINE; SPECIFICITY; PROTECTION; GENERATION; PEROXIDASE; OXIDATION; COPPER AB When Chinese hamster V79 cells are exposed to various thiol compounds in phosphate-buffered saline (PES), some compounds cause toxicity (loss of colony formation), although the dependence on drug concentration and the magnitude of the cell killing vary between the different thiols. For example: dithiothreitol (DTT) and WR-1065 cause a biphasic toxicity whereby cell killing occurs at about 0.2 to 1.0 mM thiol, but is not seen at higher or lower drug concentrations; N-acetylcysteine (NAC) is toxic only at concentrations greater than or equal to 2 mM and shows no biphasic pattern; and glutathione (GSH) and penicillamine are only minimally toxic at all concentrations. The effect of the addition of 1 mu M Cu2+ to, the thiol also depends on the particular thiol: e.g., Cu2+ increases cell killing in the biphasic pattern with WR-1065; it increases the toxicity of NAC only at high thiol concentrations; and it elicits a slight toxicity in the biphasic pattern by GSH and penicillamine. In all cases tested, if the thiol is toxic, the cell killing can be decreased or prevented by addition of catalase, consistent with the hypothesis that the toxicity is mediated through H2O2 produced during the thiol oxidation. However, when the oxidation rates of the various thiols in PBS without and with Cu2+ were measured, the data did not show a simple correlation between the toxicity of the various thiols and their oxidation rates. The rate of the reaction of the various thiols with H2O2 was also determined and showed a better, but still not good, correlation with toxicity. However, cell killing by the various thiols correlated better with the ratio between the half-lives for thiol oxidation and reaction of thiol with H2O2 than with either reaction rate alone. This suggests that the toxicity pattern and magnitude of cell killing in V79 cells by various thiols depend on the interplay between the rate of thiol oxidation and the rate of reaction between the thiol and the H2O2 produced in the thiol oxidation. C1 UNIV PENN,DEPT RADIAT ONCOL,PHILADELPHIA,PA 19104. RP HELD, KD (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA42167, CA44982] NR 24 TC 83 Z9 83 U1 1 U2 5 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 1994 VL 139 IS 1 BP 15 EP 23 DI 10.2307/3578727 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA NU848 UT WOS:A1994NU84800003 PM 8016303 ER PT J AU MIKULIS, DJ WOOD, ML ZERDONER, OAM PONCELET, BP AF MIKULIS, DJ WOOD, ML ZERDONER, OAM PONCELET, BP TI OSCILLATORY MOTION OF THE NORMAL CERVICAL SPINAL-CORD SO RADIOLOGY LA English DT Article DE BRAIN STEM, MR; MAGNETIC RESONANCE (MR), MOTION STUDIES; SPINAL CORD, MOTION; SPINAL CORD, MR ID REAL-TIME ULTRASOUND; BRAIN MOTION; DIAGNOSIS AB PURPOSE: To determine the normal pattern of cervical spinal cord motion with measurement of cervical spinal cord velocity by means of phase-contrast magnetic resonance (MR) imaging. MATERIALS AND METHODS: Spinal cord velocity was measured in 11 healthy subjects with a modified gradient-echo pulse sequence on a conventional 1.5-T MR imaging system that generated phase images sensitive to slow motion. Prospective electrocardiogram gating was used to assess velocity as a function of the cardiac cycle. The accuracy of velocity measurements was estimated with images of a phantom moving at constant velocity. RESULTS: The cervical spinal cord moves with an oscillatory pattern in the craniocaudal direction. The maximum velocity (7.0 mm/sec +/- 1.4 [standard deviation]) in the caudal direction occurred approximately 109 msec +/- 20 after electrical cardiac systole. The maximum velocities in subsequent oscillations decreased toward zero before the next cardiac systole. CONCLUSION: The cervical spinal cord oscillates in a craniocaudal direction after each cardiac systole. C1 UNIV TORONTO,DEPT RADIOL,TORONTO M5S 1A1,ON,CANADA. MASSACHUSETTS GEN HOSP,MAGNET RESONANCE RES CTR,BOSTON,MA 02114. RP MIKULIS, DJ (reprint author), TORONTO HOSP,WESTERN DIV,DEPT RADIOL,399 BATHURST ST,TORONTO M5T 2S8,ON,CANADA. NR 13 TC 57 Z9 58 U1 1 U2 5 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1994 VL 192 IS 1 BP 117 EP 121 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NT031 UT WOS:A1994NT03100022 PM 8208922 ER PT J AU JANICEK, MJ HAYES, DF KAPLAN, WD AF JANICEK, MJ HAYES, DF KAPLAN, WD TI HEALING FLARE IN SKELETAL METASTASES FROM BREAST-CANCER SO RADIOLOGY LA English DT Article DE BONE NEOPLASMS, METASTASES; BREAST NEOPLASMS ID BONE METASTASES; THERAPY; CARCINOMA; RADIOLOGY AB PURPOSE: To identify the frequency, characteristics, and prognostic significance of scintigraphically detected healing flare in patients with breast cancer metastatic to bone. MATERIALS AND METHODS: Findings on bone scans and concomitant radiographs of 1,188 patients were reviewed. Bone metastases occurred in 426 patients. Outcomes of 101 patients (aged 21-71 years) with skeletal metastases were correlated with typical scintigraphic and radiographic features. RESULTS: Healing flare with increased radiotracer uptake and radiographically demonstrated sclerotic changes in osteolytic or mixed skeletal metastases were prospectively identified in 12% of patients with skeletal metastases. Healing flare was detected 3.2 months a 1.4 after initiation of hormonal treatment or chemotherapy. Skeletal metastatic activity stabilized on bone scans within 6.2 months +/- 3.0. Patients with healing flare did not survive longer than patients without healing flare but with stable metastases after treatment (3.3 years +/- 2.0 vs 3.9 years +/- 1.6). CONCLUSION: Scintigraphically detected healing flare represents a favorable response to therapy not associated with increased survival. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,CTR BREAST EVAULAT,BOSTON,MA 02115. RP JANICEK, MJ (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT RADIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 16 TC 37 Z9 38 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 JUL PY 1994 VL 192 IS 1 BP 201 EP 204 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NT031 UT WOS:A1994NT03100036 PM 8208938 ER PT J AU JAIN, RK AF JAIN, RK TI BARRIERS TO DRUG-DELIVERY IN SOLID TUMORS SO SCIENTIFIC AMERICAN LA English DT Article ID TRANSPORT; MOLECULES C1 MASSACHUSETTS GEN HOSP,EDWIN L STEELE LAB,BOSTON,MA 02114. HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,BOSTON,MA 02115. RP JAIN, RK (reprint author), HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA, USA. NR 6 TC 666 Z9 680 U1 4 U2 69 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 SN 0036-8733 J9 SCI AM JI Sci.Am. PD JUL PY 1994 VL 271 IS 1 BP 58 EP 65 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT272 UT WOS:A1994NT27200012 PM 8066425 ER PT J AU QUAGLIANO, PV HAYES, CW PALMER, WE AF QUAGLIANO, PV HAYES, CW PALMER, WE TI VERTEBRAL PSEUDARTHROSIS ASSOCIATED WITH DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS SO SKELETAL RADIOLOGY LA English DT Article DE DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS; PSEUDARTHROSIS; ANKYLOSING SPONDYLITIS; FRACTURE; INTERVERTEBRAL DISC SPACE; BACK PAIN ID SPINE AB Diffuse idiopathic skeletal hyperostosis is an ossifying diathesis that commonly affects the vertebral skeleton. Spinal ankylosis can occur, predisposing the spine to abnormal stresses and fracture. Fracture through an ankylosed segment with continued motion at the site of fracture can result in pseudoarthrosis. Pseudoarthrosis can also develop at the junction of the fused and mobile spine secondary to chronic abnormal stresses. This complication is manifest radiographically by single-level intervertebral disc space destruction, vertebral endplate erosions, marked vertebral sclerosis, and large osteophytes. The radiographic manifestations can mimic infective spondylitis or neuropathic changes. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP QUAGLIANO, PV (reprint author), VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT DIAGNOST RADIOL,MCV STN,POB 615,RICHMOND,VA 23298, USA. NR 11 TC 10 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD JUL PY 1994 VL 23 IS 5 BP 353 EP 355 PG 3 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA PB379 UT WOS:A1994PB37900007 PM 7939834 ER PT J AU CAI, XG SZABO, P ALI, G TANZI, RE BLASS, JP AF CAI, XG SZABO, P ALI, G TANZI, RE BLASS, JP TI PSEUDOGENE OF DIHYDROLIPOYL SUCCINYLTRANSFERASE (E2K) FOUND BY PCR AMPLIFICATION AND DIRECT SEQUENCING OF RODENT HUMAN CELL HYBRID DNAS SO SOMATIC CELL AND MOLECULAR GENETICS LA English DT Note ID ALZHEIMERS-DISEASE LOCUS; GENE; CHROMOSOME; LOCALIZATION AB Previous studies have indicated that the cDNA for the E2k component of the human alpha-ketoglutarate dehydrogenase complex (KGDHC) hybridized not only to a major locus on chromosome 14q24.3 in a region associated with familial Alzheimer's disease and with Joseph-Machado disease, but also to another locus on chromosome 1p31. We now report that PCR of genomic DNA and direct sequencing indicated that the chromosome 1 locus is an intronless pseudogene. PCR of genomic DNA amplified E2k fragments from mouse-human cell hybrids containing human chromosome I DNA but not from hybrids containing human chromosome 14 DNA. The resulting amplicons were of comparable sizes to those when the cDNA was used as template. The direct sequencing of these amplicons confirmed the lack of introns and indicated a frame shift, which led to the presence of four termination codons early in the coding region. PCR followed by direct sequencing of the amplicons appears to be a convenient method for identifying intronless pseudogenes. C1 CORNELL UNIV,COLL MED,DEPT MED,NEW YORK,NY 10021. MASSACHUSETTS GEN HOSP,GENET & AGING NEUROL LAB,BOSTON,MA 02114. RP CAI, XG (reprint author), CORNELL UNIV,COLL MED,BURKE MED RES INST,WHITE PLAINS,NY 10605, USA. NR 22 TC 6 Z9 6 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0740-7750 J9 SOMAT CELL MOLEC GEN JI Somat.Cell Mol.Genet. PD JUL PY 1994 VL 20 IS 4 BP 339 EP 343 DI 10.1007/BF02254722 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA PT534 UT WOS:A1994PT53400007 PM 7974008 ER PT J AU MCGRAIL, KM OJEMANN, RG AF MCGRAIL, KM OJEMANN, RG TI THE SURGICAL-MANAGEMENT OF BENIGN INTRACRANIAL MENINGIOMAS AND ACOUSTIC NEUROMAS IN PATIENTS 70 YEARS OF AGE AND OLDER SO SURGICAL NEUROLOGY LA English DT Article DE ACOUSTIC NEUROMA; BRAIN TUMOR; CRANIOTOMY; ELDERLY; MENINGIOMA; SCHWANNOMA ID ELDERLY PATIENTS; TUMORS; ERA AB Over a 22-year-period (1967-1989) 80 patients 70 years of age and older underwent surgery for resection of a benign intracranial tumor. This group included 56 meningiomas and 24 acoustic neuromas. Forty-five of the tumors were completely excised, whereas 35 were partially removed. Tumor regrowth was documented in seven patients during the follow-up period, five of whom underwent additional surgery for resection of recurrent tumor. Thirty-six (64.3%) of the patients with meningiomas had only a minimal or no preoperative neurologic deficit, whereas twenty (35.7%) had a major deficit. Fifty-three (94.6%) patients who underwent surgery for resection of their meningioma made a good recovery (48 were improved or unchanged and five had minimal nonincapacitating worsening), one (1.8%) was worse, and two (3.6%) died. Fourteen (58.3%) of the patients with acoustic neuromas had only a minimal or no preoperative neurologic deficit, whereas 10 (41.7%) had a major deficit. Twenty-two (91.7%) of the patients who underwent surgery for resection of their acoustic neuroma made a good recovery (18 were improved or unchanged and four had minimal nonincapacitating worsening), two (8.3%) were worse, and none died. We conclude that, when indicated, surgery for intracranial meningiomas and schwannomas can be offered to patients 70 years of age and older with acceptable morbidity and mortality. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,NEUROSURG SERV,BOSTON,MA. RP MCGRAIL, KM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT NEUROSURG,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 35 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD JUL PY 1994 VL 42 IS 1 BP 2 EP 7 DI 10.1016/0090-3019(94)90241-0 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA PG227 UT WOS:A1994PG22700003 PM 7940091 ER PT J AU LEGLER, JM RYAN, LM HARVEY, EA HOLMES, LB AF LEGLER, JM RYAN, LM HARVEY, EA HOLMES, LB TI ANTICONVULSANT TERATOGENESIS .2. STATISTICAL-METHODS FOR MULTIPLE BIRTH OUTCOMES SO TERATOLOGY LA English DT Article ID SUSPECTED HUMAN TERATOGENS; LONGITUDINAL DATA-ANALYSIS; GENERALIZED LINEAR-MODELS; FETAL HYDANTOIN SYNDROME; CONGENITAL-MALFORMATIONS; CLINICAL-TRIALS; DEFECTS; ASSOCIATIONS; ANOMALIES; ENDPOINTS AB The purpose of this paper is to demonstrate the application of generalized estimating equations to assess an exposure effect using multiple birth outcomes. This multivariate approach provides the flexibility of regression modeling and improved power, as compared to series of univariate analyses or collapsing the multiple endpoints to a single indicator of affectedness. Motivating the discussion will be a large cohort study designed to assess the effects of anticonvulsant medications on a variety of birth outcomes, including major malformations, and growth and weight parameters, as well as a broad spectrum of minor physical anomalies. Because the study is still in progress, the aim here is not to present a definitive analysis, but to present and describe the application of these recently developed statistical methods to analyze studies with multiple outcomes. For simplicity, we will focus on the control and drug-exposed groups only from that study (ignoring the seizure history group), and we will concentrate on an analysis of minor physical anomalies. (C) 1994 Wiiey-Liss, Inc. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,EMBRYOL & TERATOL UNIT,BOSTON,MA 02114. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 28 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 0040-3709 J9 TERATOLOGY JI Teratology PD JUL PY 1994 VL 50 IS 1 BP 74 EP 79 DI 10.1002/tera.1420500110 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA NZ226 UT WOS:A1994NZ22600009 PM 7974257 ER PT J AU COLLEN, D STASSEN, JM YASUDA, T REFINO, C PAONI, N KEYT, B ROSKAMS, T GUERRERO, JL LIJNEN, HR GOLD, HK BENNETT, WF AF COLLEN, D STASSEN, JM YASUDA, T REFINO, C PAONI, N KEYT, B ROSKAMS, T GUERRERO, JL LIJNEN, HR GOLD, HK BENNETT, WF TI COMPARATIVE THROMBOLYTIC PROPERTIES OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR AND OF A PLASMINOGEN-ACTIVATOR INHIBITOR-1-RESISTANT GLYCOSYLATION VARIANT, IN A COMBINED ARTERIAL AND VENOUS THROMBOSIS MODEL IN THE DOG SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID ANTIPLATELET GPIIB/IIIA ANTIBODY; COMBINED BOLUS INJECTION; PHARMACOKINETIC PROPERTIES; PROLONGED CLEARANCE; CANINE PREPARATION; HUMAN-PLASMA; UROKINASE; DELETION; MUTANTS; FORMS AB rt-PA-K, a variant of recombinant tissue-type plasminogen activator (rt-PA) with substitution of amino acids 296 to 299 with alanine (KHRR296-299AAAA) has increased fibrin-specificity and reduced sensitivity to plasminogen activator inhibitor-1; rt-PA-T, with threonine 103 replaced by asparagine has an additional glycosylation site and a reduced clearance; and rt-PA-N, with asparagine 117 mutagenized to glutamine lacks the high mannose carbohydrate side chain. We have investigated whether combination of these properties in a single molecule might yield an improved thrombolytic agent. The thrombolytic potency and fibrin-specificity of the combination mutant rt-PA-TNK was compared with that of rt-PA in a combined venous whole blood clot model and platelet-rich arterial eversion graft thrombosis model in dogs given intravenous heparin and aspirin. Infusion of 0.125 to 1.0 mg/kg over 60 min in groups of 4 to 5 dogs produced dose-dependent fibrin-specific venous clot lysis. The thrombolytic potency (percent lysis per mg compound administered per kg body weight) of rt-PA-TNK was significantly higher than that of rt-PA as evidenced by a higher maximal rate of lysis of 480 +/- 100% versus 140 +/- 40% within the 2 h observation period per mg of compound administered per kg body weight (mean +/- SEM, p = 0.004) and a significantly lower dose of 0.08 +/- 0.01 versus 0.21 +/- 0.04 mg/kg body weight at which the maximal rate of lysis was obtained (p = 0.004). This higher thrombolytic potency was the result of a significantly reduced clearance (240 +/- 32 versus 540 +/- 49 ml/min, p = 0.002) and a similar specific thrombolytic activity (percent lysis per mu g/ml plasma antigen level). Arterial reflow was obtained with 1 mg/kg rt-PA and with 0.5 mg/kg rt-PA-TNK, but with each agent recanalization was consistently associated with cyclic reocclusion and reflow. The frequency of arterial recanalization was somewhat higher with rt-PA-TNK (10/12) than with rt-PA (4/12) (p = 0.07) but the total patency times during a 2 h observation period were similar. Thus, rt-PA-TNK has an approximately 3-fold higher thrombolytic potency for whole blood clot lysis than rt-PA. The activity ratio of rt-PA-TNK to rt-PA is, however, 2.5-fold higher in human in vitro plasma clot lysis systems than in canine systems, suggesting that the thrombolytic potency of rt-PA-TNK in man could be up to 8-fold higher than that of rt-PA. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DIV CARDIOL,BOSTON,MA. GENENTECH INC,DEPT CARDIOVASC PHARMACOL,S SAN FRANCISCO,CA. CATHOLIC UNIV LEUVEN,DEPT PATHOL,LOUVAIN,BELGIUM. RP COLLEN, D (reprint author), CATHOLIC UNIV LEUVEN,CTR MOLEC & VASC BIOL,CAMPUS GASTHUISBERG,BLDG TEACHING & RES,HERESTR 4,B-3000 LOUVAIN,BELGIUM. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 26 TC 58 Z9 59 U1 0 U2 1 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL PY 1994 VL 72 IS 1 BP 98 EP 104 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA NW435 UT WOS:A1994NW43500017 PM 7974384 ER PT J AU AVRUCH, J ZHANG, XF KYRIAKIS, JM AF AVRUCH, J ZHANG, XF KYRIAKIS, JM TI RAF MEETS RAS - COMPLETING THE FRAMEWORK OF A SIGNAL-TRANSDUCTION PATHWAY SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID PROTEIN-KINASE KINASE; MAP KINASE; ACTIVATION; PHOSPHORYLATION; CELLS; TRANSFORMATION; REQUIREMENT; P21(RAS); INVITRO AB The Ras oncoprotein, a GTP-activated molecular switch, interacts directly with the Raf oncoprotein to recruit the MAP kinases and their subordinates. In this way, a mitogenic signal initiated by tyrosine kinases is converted by Ras into a wave of regulatory phosphorylation on serine and threonine residues that, depending on its intensity and duration, and the variety of substrates available, results in cell differentiation or cell division. C1 MASSACHUSETTS GEN HOSP,MED SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02114. RP AVRUCH, J (reprint author), MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02114, USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 43 TC 528 Z9 530 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 1994 VL 19 IS 7 BP 279 EP 283 DI 10.1016/0968-0004(94)90005-1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY061 UT WOS:A1994NY06100005 PM 8048167 ER PT J AU MYERS, MG SUN, XJ WHITE, MF AF MYERS, MG SUN, XJ WHITE, MF TI THE IRS-1 SIGNALING SYSTEM SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID INSULIN-RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE KINASES; SH2 DOMAINS; HEMATOPOIETIC-CELLS; PROTEIN; EXPRESSION; SRC; RAS; PHOSPHORYLATION AB Insulin-receptor substrate 1 (IRS-1) is a principal substrate of the receptor tyrosine kinase for insulin and insulin-like growth factor 1, and a substrate for a tyrosine kinase activated by interleukin 4. IRS-1 undergoes multisite tyrosine phosphorylation and mediates downstream signals by 'docking' various proteins that contain Src homology 2 domains. IRS-1 appears to be a unique molecule; however, 4PS, a protein found mainly in hemopoietic cells, may represent another member of this family. C1 HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02215. RP MYERS, MG (reprint author), JOSLIN DIABET CTR,DIV RES,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK 38712, DK 43808] NR 42 TC 286 Z9 289 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 1994 VL 19 IS 7 BP 289 EP 293 DI 10.1016/0968-0004(94)90007-8 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NY061 UT WOS:A1994NY06100007 PM 8048169 ER PT J AU BURKE, TR NOMIZU, M OTAKA, A SMYTH, MS ROLLER, PP CASE, RD WOLF, G SHOELSON, SE AF BURKE, TR NOMIZU, M OTAKA, A SMYTH, MS ROLLER, PP CASE, RD WOLF, G SHOELSON, SE TI CYCLIC PEPTIDE INHIBITORS OF PHOSPHATIDYLINOSITOL 3-KINASE P85 SH2 DOMAIN BINDING SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; SOLID-PHASE SYNTHESIS; RECEPTOR; TARGETS; ANALOGS; KINASE AB Cyclic hexameric peptides based on the amino acid sequence ''Gly-Xxx-Val-Pro-Met-Leu'', where Xxx Is either phosphotyrosyl (pTyr) residue or a hydrolytically stable pTyr mimetic, were examined for their ability to bind to the C-terminal SH2 domain of the p85 phosphoinositol 3-kinase (PI 3-kinase). The cyclic peptides retained significant binding affinity relative to their linear counterparts. Potency varied depending on Xxx in the order: phosphonomethyl phenylalanine (Pmp, ID50 = 5.2 mu M) < phosphonodifluoromethyl phenylalanine (F(2)Pmp, ID50 = 2.2 mu M) < pTyr (ID50 = 1.0 mu M), With Xxx = Tyr being inactive (ID50 > 500 M). Greatly reduced potency was observed when Xxx was of the unnatural D-configuration. The cyclic peptides represent conformationally constrained ligands which should be useful in the development of p85 SH2 domain-directed inhibitors. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP BURKE, TR (reprint author), NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 28 TC 18 Z9 18 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 JUN 30 PY 1994 VL 201 IS 3 BP 1148 EP 1153 DI 10.1006/bbrc.1994.1825 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NU977 UT WOS:A1994NU97700014 PM 8024556 ER PT J AU GUERINA, NG HSU, HW MEISSNER, HC MAGUIRE, JH LYNFIELD, R STECHENBERG, B ABROMS, I PASTERNACK, MS HOFF, R EATON, RB GRADY, GF CHEESEMAN, SH MCINTOSH, K MEDEARIS, DN ROBB, R WEIBLEN, BJ AF GUERINA, NG HSU, HW MEISSNER, HC MAGUIRE, JH LYNFIELD, R STECHENBERG, B ABROMS, I PASTERNACK, MS HOFF, R EATON, RB GRADY, GF CHEESEMAN, SH MCINTOSH, K MEDEARIS, DN ROBB, R WEIBLEN, BJ TI NEONATAL SEROLOGIC SCREENING AND EARLY TREATMENT FOR CONGENITAL TOXOPLASMA-GONDII INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TISSUE-CULTURE; PREGNANCIES; MANAGEMENT AB Background. Most infants with congenital Toxoplasma gondii infection have no symptoms at birth, but many will have retinal disease or neurologic abnormalities later in life. Early detection and treatment of congenital toxoplasmosis may reduce these sequelae. Methods. In Massachusetts since January 1986, and in New Hampshire since July 1988, newborns have been screened for intrauterine infection with T. gondii by means of an IgM capture immunoassay of blood specimens routinely collected for screening for metabolic disorders. Congenital infection is confirmed by assays for specific IgG and IgM antibodies in serum from infants and their mothers. For this study, infants with serologic evidence of infection underwent extensive clinical evaluation and received one year of treatment. Results. Through June 1992, 100 of 635,000 infants tested had positive screening tests. Congenital infection was confirmed in 52 infants, 50 of whom were identified only through neonatal screening and not through initial clinical examination. However, after the serologic results became available, more detailed examinations revealed abnormalities of either the central nervous system or the retina in 19 of 48 infants evaluated (40 percent). After treatment, only 1 of 46 children had a neurologic deficit (hemiplegia attributable to a cerebral lesion present at birth). Thirty-nine treated children had follow-up ophthalmologic examinations when one to six years old; four (10 percent) had eye lesions that may have developed postnatally (a macular lesion in one child and minor retinal scars in three). Conclusions. Routine neonatal screening for toxoplasmosis identifies congenital infections that are subclinical, and early treatment may reduce the severe long-term sequelae. C1 CHILDRENS HOSP,DIV INFECT DIS,BOSTON,MA 02115. CHILDRENS HOSP,DIV NEWBORN MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NEWTON WELLESLEY HOSP,DIV NEONATOL,NEWTON,MA. MASSACHUSETTS STATE LAB INST,NEW ENGLAND REG NEWBORN SCREENING PROGRAM,BOSTON,MA. TUFTS UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02111. BRIGHAM & WOMENS HOSP,DEPT INFECT DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,PEDIAT INFECT DIS UNIT,BOSTON,MA 02114. BAYSTATE MED CTR,DIV PEDIAT INFECT DIS,SPRINGFIELD,MA 01107. UNIV MASSACHUSETTS,MED CTR,DEPT NEUROL,WORCESTER,MA 01655. RP GUERINA, NG (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,DEPT PEDIAT INFECT DIS,DIV NEWBORN MED,NEMC 44,750 WASHINGTON ST,BOSTON,MA 02111, USA. NR 19 TC 239 Z9 257 U1 1 U2 14 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 JUN 30 PY 1994 VL 330 IS 26 BP 1858 EP 1863 DI 10.1056/NEJM199406303302604 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NT530 UT WOS:A1994NT53000004 PM 7818637 ER PT J AU MILLS, JA AF MILLS, JA TI MEDICAL PROGRESS - SYSTEMIC LUPUS-ERYTHEMATOSUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID CONNECTIVE-TISSUE DISEASE; CENTRAL-NERVOUS-SYSTEM; HISTOCOMPATIBILITY COMPLEX GENES; PULSE CYCLOPHOSPHAMIDE; IMMUNE-COMPLEXES; CONTROLLED TRIAL; LONG-TERM; INTRAVENOUS CYCLOPHOSPHAMIDE; ANTIPHOSPHOLIPID ANTIBODIES; CLINICAL-SIGNIFICANCE C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP MILLS, JA (reprint author), MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,BOSTON,MA 02114, USA. NR 134 TC 306 Z9 318 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 JUN 30 PY 1994 VL 330 IS 26 BP 1871 EP 1879 DI 10.1056/NEJM199406303302608 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA NT530 UT WOS:A1994NT53000008 PM 8196732 ER PT J AU SPRINCE, NL OLIVER, LC CHAMBERLIN, RI EISEN, EA GREENE, RE AF SPRINCE, NL OLIVER, LC CHAMBERLIN, RI EISEN, EA GREENE, RE TI ETIOLOGY AND PATHOGENESIS OF HARD METAL DISEASE SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Note DE COBALT; TUNGSTEN CARBIDE; INTERSTITIAL LUNG DISEASE C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. UNIV MASSACHUSETTS,LOWELL,MA. RP SPRINCE, NL (reprint author), UNIV IOWA,COLL MED,IOWA CITY,IA 52242, USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD JUN 30 PY 1994 VL 150 IS 1-3 BP 55 EP 55 DI 10.1016/0048-9697(94)90128-7 PG 1 WC Environmental Sciences SC Environmental Sciences & Ecology GA NW215 UT WOS:A1994NW21500005 ER PT J AU LIPSITZ, SR FITZMAURICE, GM AF LIPSITZ, SR FITZMAURICE, GM TI SAMPLE-SIZE FOR REPEATED-MEASURES STUDIES WITH BINARY RESPONSES SO STATISTICS IN MEDICINE LA English DT Article ID CATEGORICAL-DATA ANALYSIS; LOG LINEAR-MODEL; LOGISTIC-REGRESSION; REFLECTIONS; EFFICIENCY; DESIGN AB We consider the sample size required for repeated measures studies when the response variable is binary. We propose the use of weighted least squares (WLS) for calculating the minimum sample size required to detect some minimum clinically important treatment effect. We provide tabulated values of the estimated sample sizes for a simple example and we discuss some practical considerations in determination of sample size with repeated binary responses. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. RP LIPSITZ, SR (reprint author), HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIEHS NIH HHS [ES07142]; NIGMS NIH HHS [GM29745]; NIMH NIH HHS [MH17119] NR 15 TC 21 Z9 21 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 1994 VL 13 IS 12 BP 1233 EP 1239 DI 10.1002/sim.4780131205 PG 7 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NX267 UT WOS:A1994NX26700004 PM 7973204 ER PT J AU SUGA, H ERSOY, O WILLIAMS, SF TSUMURAYA, T MARGOLIES, MN SINSKEY, AJ MASAMUNE, S AF SUGA, H ERSOY, O WILLIAMS, SF TSUMURAYA, T MARGOLIES, MN SINSKEY, AJ MASAMUNE, S TI CATALYTIC ANTIBODIES GENERATED VIA HETEROLOGOUS IMMUNIZATION SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID ORIGINAL ANTIGENIC SIN; CELLS; SPECIFICITY; HYDROLYSIS; REPERTOIRE; MUTATION C1 MIT,DEPT CHEM,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. NR 25 TC 31 Z9 33 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUN 29 PY 1994 VL 116 IS 13 BP 6025 EP 6026 DI 10.1021/ja00092a086 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA NV421 UT WOS:A1994NV42100086 ER PT J AU BENHAMOU, PY WATT, PC MULLEN, Y INGLES, S WATANABE, Y NOMURA, Y HOBER, C MIYAMOTO, M KENMOCHI, T PASSARO, EP ZINNER, MJ BRUNICARDI, FC AF BENHAMOU, PY WATT, PC MULLEN, Y INGLES, S WATANABE, Y NOMURA, Y HOBER, C MIYAMOTO, M KENMOCHI, T PASSARO, EP ZINNER, MJ BRUNICARDI, FC TI HUMAN ISLET ISOLATION IN 104 CONSECUTIVE CASES - FACTORS AFFECTING ISOLATION SUCCESS SO TRANSPLANTATION LA English DT Article ID PANCREATIC-ISLETS; ACUTE STROKE; TRANSPLANTATION; HYPERGLYCEMIA; LANGERHANS; VIABILITY; ANIMALS; TYPE-1; RATS AB One of the major steps toward successful islet trans plantation for the treatment of type diabetes is to obtain islets of sufficient number and viability. Using a standardized method of isolating islets, the goal of this study was to analyze the factors influencing the outcome of islet isolation. A total of 104 cadaveric human pancreata were processed for islets by the same team. Data from the islet-processing charts were reviewed retrospectively. The two endpoints were the recovery of islets, viable after 2 days of culture (group V=viable, group NV=nonviable) and the islet yield. Viable islets were recovered in 61% of cases (n=63). Minimal blood glucose recorded during hospitalization was very significantly lower in group V (124+/-5 vs. 148+/-9, P=0.01). Lack of significant medical history in the donor was associated with better viability as compared with vari ous donor predispositions (chi-(2) 4.21, P=0.04). Cold ischemia time (8.1+/-0.5 hr in group V vs. 9.8+/-0.9 hr in group NV, P=0.07) and collagenase lot (5 lots tested, chi-(2) 13.1, P=0.01) also affected the recovery of viable islets. Hospital time was shorter in group V (65.3+/-6.8 vs. 80.9+/-17.9 hr, P=0.35). Multivariate logistic regression analyses of viable islet recovery identified minimal blood glucose (P=0.03) and collagenase lot (P=0.06) as the most significant risk factors. However, the best multivariate predictive model-which includes blood glucose, collagenase lot, donor age and surgical procurement team-correctly predicted 66.2% of cases only. Multivariate analysis of final islet yield designed hospitalization length, cardiorespiratory arrest, surgical procurement team, and collagenase lot as the best predictors. These data obtained in a large series of pancreata emphasized several donor and technical factors that should target the attention of islet transplant researchers in order to improve islet yield and viability. C1 UNIV CALIF LOS ANGELES,SCH MED,DIABET RES CTR,DEPT SURG,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DIABET RES CTR,DEPT BIOMATH,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DEPT SURG,LOS ANGELES,CA 90024. NR 23 TC 99 Z9 102 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 1994 VL 57 IS 12 BP 1804 EP 1810 DI 10.1097/00007890-199457120-00021 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NV568 UT WOS:A1994NV56800021 PM 8016887 ER PT J AU SCHNITZER, JJ ROY, SM AF SCHNITZER, JJ ROY, SM TI HEALTH-SERVICES IN GAZA UNDER THE AUTONOMY PLAN SO LANCET LA English DT Article ID WEST BANK; ISRAEL AB The Gaza Strip now has limited self-rule. Its people inherit a health-care system provided by four sectors-the Israeli government, the UN Relief and Works Agency, nongovernmental organisations, and private facilities. They also inherit a legacy of health indices comparing unfavourably with those of Israel, huge numbers of refugees, a looming water crisis, civil unrest, and a health care expenditure bill (as a proportion of gross domestic product) that will be unsustainable. Four plans have been drawn up for health services in autonomous Gaza but none is exactly right. C1 HARVARD UNIV,CTR MIDDLE EASTERN STUDIES,CAMBRIDGE,MA 02138. RP SCHNITZER, JJ (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT SURG SERV,BOSTON,MA 02114, USA. NR 27 TC 2 Z9 2 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 JUN 25 PY 1994 VL 343 IS 8913 BP 1614 EP 1617 DI 10.1016/S0140-6736(94)93063-5 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NU354 UT WOS:A1994NU35400016 PM 7911926 ER PT J AU FLEISCHMANN, J CAMPBELL, DA AF FLEISCHMANN, J CAMPBELL, DA TI EXPRESSION OF THE LEISHMANIA-TARENTOLAE UBIQUITIN-ENCODING AND MINI-EXON GENES SO GENE LA English DT Article DE CHROMOSOME LOCATION; KINETOPLASTID; MESSENGER-RNA; SPLICED LEADER; TRYPANOSOMATID; GECKO ID TRYPANOSOMA-BRUCEI; RNA GENE; GENOMIC ORGANIZATION; NUCLEOTIDE-SEQUENCE; POLYUBIQUITIN GENE; MESSENGER-RNAS; TRANSCRIPTION; CHROMOSOMES; CALMODULIN; DONOVANI AB To develop models for transcription and trans-splicing in kinetoplastid protozoa, we have characterized ubiquitin (Ubi) gene organization and mRNA processing in Leishmania tarentolae (Lt). Three ubi loci were characterized: two discrete Ubi-extension protein 52 (EP52)-encoding genes (ubiA and ubiB) and a polymorphic polyubiquitin-encoding gene (ubiC). The three loci resided on chromosomes of 2.05 Mb, 630 kb and 2.9 Mb, respectively. On the basis of upstream flanking gene identity, ubiB appears to be the homologue of the tandemly repeated ubi-EP52/1 and 2 in Trypanosoma brucei (Tb). Similar to Trypanosoma cruzi, Lt did not contain a homologue of the ubi-EP76 that has been found in Saccharomyces cerevisiae and multicellular organisms. All three Lt ubi loci were transcribed. The primary transcripts from the ubi loci were processed at the 5'-end by trans-splicing with the mini-exon. A Lt mini-exon gene (min) that gave rise to a 95-nt primary transcript, which is the second template in the trans-splicing reaction, was also characterized. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,LOS ANGELES,CA 90073. NR 24 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 24 PY 1994 VL 144 IS 1 BP 45 EP 51 DI 10.1016/0378-1119(94)90201-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA NW550 UT WOS:A1994NW55000007 PM 8026757 ER PT J AU WU, GD CHEN, LL FORSLUND, K TRABER, PG AF WU, GD CHEN, LL FORSLUND, K TRABER, PG TI HEPATOCYTE NUCLEAR FACTOR-1-ALPHA (HNF-1-ALPHA) AND HNF-1-BETA REGULATE TRANSCRIPTION VIA 2 ELEMENTS IN AN INTESTINE-SPECIFIC PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUCRASE-ISOMALTASE GENE; HUMAN-COLON CARCINOMA; DNA-BINDING PROTEINS; CRYPT-VILLUS AXIS; MESSENGER-RNA; MOLECULAR-CLONING; LEUCINE ZIPPER; CELL-LINE; FACTOR-I; EXPRESSION AB Hepatocyte nuclear factor-1 alpha (HNF-1 alpha) and HNF-1 beta are transcription factors that contain a divergent homeodomain, bind to DNA as homo- or heterodimers, and act to regulate transcription of many genes that are expressed primarily in liver. We show that HNF-1 alpha and HNF-1 beta act as regulatory factors for transcription of sucrase-isomaltase (SI), the gene for which is expressed exclusively in absorptive enterocytes of the small intestine. HNF-1 alpha and HNF-1 beta bind to two evolutionarily conserved sites in the SI promoter, previously named SIF2 and SIF3, with different relative affinities. HNF-1 alpha binds to the SIF3 element with greater affinity than to the SIF2 element, whereas HNF-1 beta binds to both elements equally. Co-transfection experiments demonstrated that HNF-1 alpha is able to increase transcriptional initiation from a minimal SI intestine-specific promoter. In contrast, HNF-1 beta has no functional effect on transcription of the SI promoter. The functional and DNA binding differences of HNF-1 alpha and HNF-1 beta on elements in the SI promoter suggest that these transcription factors may play a role in the complex spatial patterns of SI gene expression in the intestine. C1 UNIV PENN, SCH MED, DEPT INTERNAL MED, DIV GASTROENTEROL, PHILADELPHIA, PA 19104 USA. DEPT VET AFFAIRS MED CTR, PHILADELPHIA, PA 19104 USA. FU NIDDK NIH HHS [DK44621] NR 40 TC 104 Z9 106 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 1994 VL 269 IS 25 BP 17080 EP 17085 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NT846 UT WOS:A1994NT84600018 PM 8006012 ER PT J AU LI, XP ABDI, K MENTZER, SJ AF LI, XP ABDI, K MENTZER, SJ TI O-PHTHALDEHYDE FLUORESCENCE MICROASSAY FOR THE DETERMINATION OF ANTIBODY CONCENTRATION SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE PURIFICATION; MONOCLONAL ANTIBODY; FLUORESCENCE; MICROASSAY; O-PHTHALDEHYDE ID AMINO-ACIDS; PROTEIN; QUANTITATION; LOWRY AB o-Phthaldehyde (OPA) reagent reacts with primary amines in aqueous solution at room temperature. When the reaction occurs in the presence of 2-mercaptoethanol, a bright blue fluorescence is produced. We investigated the application of the OPA reagent in the routine determination of monoclonal antibody concentration. The OPA reagent produced maximal fluorescence within 30 min and was stable for 2 h. Buffers containing primary amines gave high background fluorescence; however, the OPA reagent gave reliable results with the most commonly used antibody solutions. The OPA reagent provided a rapid and simple measure of protein concentration from 1 mu g to 1 mg and was readily adapted for use with a 96-well fluorescence reader. C1 BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NHLBI NIH HHS [HL47078] NR 8 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 24 PY 1994 VL 172 IS 2 BP 141 EP 145 DI 10.1016/0022-1759(94)90101-5 PG 5 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA NW873 UT WOS:A1994NW87300001 PM 8034969 ER PT J AU WANG, TC CARDIFF, RD ZUKERBERG, L LEES, E ARNOLD, A SCHMIDT, EV AF WANG, TC CARDIFF, RD ZUKERBERG, L LEES, E ARNOLD, A SCHMIDT, EV TI MAMMARY HYPERPLASIA AND CARCINOMA IN MMTV-CYCLIN D1 TRANSGENIC MICE SO NATURE LA English DT Article ID CELL-CYCLE; MOUSE STRAIN; ONCOGENE; PROTEIN; EXPRESSION; GENE; INT-2; CHROMOSOME-11Q13; OVEREXPRESSION; ABNORMALITIES AB Physical associations between cyclins, viral oncogenes and tumour suppressor genes imply a central role for cyclins in growth control(1,2). Cyclin D1 was identified as a candidate oncogene (PRAD1) in tumour-specific DNA rearrangements(3,4) and is suspected to be a contributor to several types of neoplasms including breast cancer(5,6). Cyclin D1 also rescues G1 cyclin-defective Saccharomyces cerevisiae(7), and is a growth-regulated genes. Despite evidence suggesting that cyclin D1 is an oncogene, its ability to transform cells directly in culture remains controversial(9-16). To evaluate its potential to deregulate growth in vivo in a physiologically relevant tissue we overexpressed cyclin D1 in mammary cells in transgenic mice. We report here that overexpression of cyclin D1 resulted in abnormal mammary cell proliferation including the development of mammary adenocarcinomas. We conclude that overexpression of cyclin D1 deregulates cell proliferation and can induce tumorigenic changes in mammary tissues, suggesting that cyclin D1 indeed plays an important oncogenic role in breast cancer. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. UNIV CALIF DAVIS,SCH MED,DEPT PATHOL,DAVIS,CA 95616. MASSACHUSETTS GEN HOSP,DEPT MED,ENDOCRINE ONCOL LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114. NR 25 TC 835 Z9 843 U1 1 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUN 23 PY 1994 VL 369 IS 6482 BP 669 EP 671 DI 10.1038/369669a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT459 UT WOS:A1994NT45900061 PM 8208295 ER PT J AU KRAUT, JA COBURN, JW AF KRAUT, JA COBURN, JW TI BONE, ACID, AND OSTEOPOROSIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SODIUM-BICARBONATE; CALCIUM BALANCE; WOMEN RP KRAUT, JA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90072, USA. NR 10 TC 22 Z9 22 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 JUN 23 PY 1994 VL 330 IS 25 BP 1821 EP 1822 DI 10.1056/NEJM199406233302510 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NR295 UT WOS:A1994NR29500010 PM 8190161 ER PT J AU CHEN, SY KHOURI, Y BAGLEY, J MARASCO, WA AF CHEN, SY KHOURI, Y BAGLEY, J MARASCO, WA TI COMBINED INTRACELLULAR AND EXTRACELLULAR IMMUNIZATION AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION WITH A HUMAN ANTI-GP120 ANTIBODY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS 1 ENVELOPE PROTEIN; INTRACELLULAR ANTIBODY AND IMMUNIZATION; AIDS; GENE THERAPY; CD4+ T CELLS ID HTLV-III/LAV ENVELOPE; MONOCLONAL-ANTIBODY; GLYCOPROTEIN; HIV-1; MUTANTS; CELLS; REPLICATION; EXPRESSION; RECEPTOR; AIDS AB In this study, a human CD4(+) T lymphocyte line was transduced to secrete Fab fragments of a broadly neutralizing human monoclonal antibody F105 that reacts with the CD4-binding site of human immunodeficiency virus type 1 (HIV-1) envelope protein. In the transduced cells infected with HIV-1, the nascent Fab fragments bind intracellularly to the HIV-1 envelope protein and inhibit HIV-1 production. The secreted Fab fragments are able to neutralize cell-free HIV-1. In addition, the nascent Fab fragments can inhibit HIV-1 production by binding intracellularly to envelope mutants that escape neutralization by extracellular F105 antibody. The combined intra- and extracellular binding activities of the expressed Fab fragments result in the efficient blocking of cytopathic syncytium formation and infectious virus production. Thus, these antibody-producing T lymphocytes are not only resistant to HIV-1 infection but also can protect surrounding lymphocytes by secreting neutralizing antibodies. This novel strategy of combining intracellular and extracellular immunization may be useful for gene therapy of AIDS and other diseases. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV HUMAN RETROVIROL,BOSTON,MA 02115. FU NCI NIH HHS [P30CA06516]; NIAID NIH HHS [AI28785, P30AI28691] NR 23 TC 66 Z9 67 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 5932 EP 5936 DI 10.1073/pnas.91.13.5932 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100041 PM 8016092 ER PT J AU EBISAWA, T KARNE, S LERNER, MR REPPERT, SM AF EBISAWA, T KARNE, S LERNER, MR REPPERT, SM TI EXPRESSION CLONING OF A HIGH-AFFINITY MELATONIN RECEPTOR FROM XENOPUS DERMAL MELANOPHORES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID G-PROTEIN; ADENYLATE-CYCLASE; LIGAND-BINDING; SEQUENCE; INHIBITION; SYSTEMS; SITES; BRAIN AB Using an expression cloning strategy, a high-affinity melatonin receptor cDNA has been isolated from Xenopus laevis dermal melanophores. Transient expression of the cDNA in COS-7 cells resulted in high-affinity 2-[I-125]- iodomelatonin binding (K-d = 6.3 +/- 0.3 X 10(-11) M). In addition, six ligands exhibited a rank order of inhibition of specific 2-[I-125] iodomelatonin binding that was identical to that reported for endogenous high-affinity receptors. Functional studies of CHO cells stably expressing the receptor cDNA showed that melatonin acting through the cloned receptor inhibited forskolin-stimulated cAMP accumulation in a dose-dependent manner. Northern blot analysis showed that melatonin receptor transcripts are moderately expressed in Xenopus dermal melanophores. The cDNA encodes a protein of 420 amino acids, which contains seven hydrophobic segments. Structural analysis revealed that the receptor protein is a newly discovered member of the guanine nucleotide binding protein-coupled receptor family. C1 MASSACHUSETTS GEN HOSP, CHILDRENS SERV, DEV CHRONOBIOL LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. YALE UNIV, SCH MED, INTERDEPT NEUROSCI PROGRAM, NEW HAVEN, CT 06510 USA. YALE UNIV, SCH MED, DEPT INTERNAL MED, NEW HAVEN, CT 06510 USA. YALE UNIV, SCH MED, HOWARD HUGHES MED INST, NEW HAVEN, CT 06510 USA. FU NIDDK NIH HHS [DK 42125] NR 35 TC 350 Z9 362 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 6133 EP 6137 DI 10.1073/pnas.91.13.6133 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100082 PM 7517042 ER PT J AU CUOMO, CA KIRCH, SA GYURIS, J BRENT, R OETTINGER, MA AF CUOMO, CA KIRCH, SA GYURIS, J BRENT, R OETTINGER, MA TI RCH1, A PROTEIN THAT SPECIFICALLY INTERACTS WITH THE RAG-1 RECOMBINATION-ACTIVATING PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STRAND BREAK REPAIR; V(D)J RECOMBINATION; SCID MUTATION; MICE; PHOSPHATASE; DEFICIENCY; MUTANTS; GENES; MOUSE AB RAG1 and R4G2 are lymphoid-specific genes that together induce V(D)J recombinase activity in a variety of nonlymphoid cell types. While no other lymphoid-specific factors are required to induce recombination, other factors with more widespread expression patterns have been implicated in the reaction. However, none of these factors have been cloned, and their relationship to the RAG proteins is unclear. Using the yeast two-hybrid assay, we have identified RCH1, a gene encoding a protein of molecular weight 58,000 that interacts specifically with RAG-1. The predicted Rch1 protein sequence is 47% identical to yeast SRP1, a protein associated with the nuclear envelope. A truncated form of Rch1, which retains the ability to interact with RAG-1, reduces V(D)J recombination activity in HeLa cells. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,PROGRAM CELL & DEV BIOL,CAMBRIDGE,MA 02138. FU NIGMS NIH HHS [GM48026] NR 27 TC 167 Z9 171 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 6156 EP 6160 DI 10.1073/pnas.91.13.6156 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100087 PM 8016130 ER PT J AU AIELLO, LP ROBINSON, GS LIN, YW NISHIO, Y KING, GL AF AIELLO, LP ROBINSON, GS LIN, YW NISHIO, Y KING, GL TI IDENTIFICATION OF MULTIPLE GENES IN BOVINE RETINAL PERICYTES ALTERED BY EXPOSURE TO ELEVATED LEVELS OF GLUCOSE BY USING MESSENGER-RNA DIFFERENTIAL DISPLAY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SMOOTH-MUSCLE CELLS; DEPENDENT DIABETES-MELLITUS; HUMAN-BREAST-CANCER; ENDOTHELIAL-CELLS; BASEMENT-MEMBRANE; MESSENGER-RNAS; CALDESMON-BINDING; SKELETAL-MUSCLE; PROTEIN-KINASE; CDNA CLONES AB Loss of capillary pericytes, a characteristic finding in diabetic retinopathy, is strongly associated with hyperglycemia. The pathologic aberrations associated with diabetic retinopathy are localized primarily in the retinal capillaries and are only poorly reversed by subsequent euglycemic control. Since hyperglycemia significantly inhibits pericyte growth in culture, we investigated the regulation of gene expression in retinal pericytes exposed to physiologic (5.5 mM) and pathologic (20 mM) glucose concentrations. By utilizing modifications of the mRNA differential display technique, over 14,000 mRNA species were screened, and 35 candidate clones were obtained. Partial DNA sequence demonstrated that 25 of these were distinct genes, including 7 known, 16 previously unreported, and 2 sequences with known homologues. Northern blot analysis demonstrated altered gene expression in 10 (40%), undetectable signals in 12 (48%), and nonregulation in 3 (12%). Genes with glucose-regulated expression included those encoding fibronectin (51% +/- 15%, P = 0.003; mean percentage of control +/- SD), caldesmon (68% +/- 18%; P = 0.026), two ribosomal proteins (201% +/- 72%, P = 0.011; 136% +/- 16%, P = 0.036), Rieske FeS reductase (66% +/- 17%; P = 0.029), three previously unreported sequences (57%, 167%, 271%), and molecules homologous to autoantigens (213%) and tyrosine kinases (down 16- to 33-fold). Caldesmon protein concentrations in pericytes and smooth muscle cells demonstrated decreases by Western blot analysis concordant with mRNA levels. These studies identify genes whose expression is significantly altered after 7 days of exposure to elevated glucose levels and provide new targets for understanding the adverse effects of hyperglycemia on vascular cells. In addition, this study provides strong support for the use of differential mRNA display as a method to rapidly isolate differentially expressed genes in metabolic systems. C1 JOSLIN DIABET CTR, DIV RES, BOSTON, MA 02215 USA. BEETHAM EYE INST, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. DANA FARBER CANC INST, DEPT CELLULAR & MOLEC BIOL, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DEPT MED, BOSTON, MA 02115 USA. FU NEI NIH HHS [EY05110]; NIDDK NIH HHS [DK07260]; PHS HHS [36836] NR 61 TC 103 Z9 105 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 6231 EP 6235 DI 10.1073/pnas.91.13.6231 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100102 PM 8016144 ER PT J AU BERGELSON, JM CHAN, M SOLOMON, KR STJOHN, NF LIN, HM FINBERG, RW AF BERGELSON, JM CHAN, M SOLOMON, KR STJOHN, NF LIN, HM FINBERG, RW TI DECAY-ACCELERATING FACTOR (CD55), A GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED COMPLEMENT REGULATORY PROTEIN, IS A RECEPTOR FOR SEVERAL ECHOVIRUSES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE VIRUS RECEPTOR; PICORNAVIRUS; ECHOVIRUS 7 ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; TYROSINE KINASES; INTEGRIN VLA-2; MEMBRANE; MOLECULES; CAVEOLAE; CELLS; IDENTIFICATION; ENDOCYTOSIS; CLONING AB Echoviruses are human pathogens belonging to the picornavirus family. Decay-accelerating fatter (DAF) is a glycosylphosphatidylinositol (GPI)-anchored surface protein that protects cells from lysis by autologous complement. Anti-DAF monoclonal antibodies prevented echovirus 7 attachment to susceptible cells and protected cells from infection. HeLa cells specifically lost the capacity to bind echovirus 7 when treated with phosphatidylinositol-specific phospholipase C, an enzyme that releases GPI-anchored proteins from the cell surface, indicating that the virus receptor, like DAF, is a GPI-anchored protein. Although Chinese hamster ovary cells do not bind echovirus 7, transfectants expressing human DAF bound virus efficiently, and binding was prevented by pretreatment with an anti-DAF monoclonal antibody. Anti-DAF antibodies prevented infection by at least six echovirus serotypes. These results indicate that DAF is the receptor mediating attachment and infection by several echoviruses. RP BERGELSON, JM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115, USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI31628] NR 29 TC 222 Z9 229 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 1994 VL 91 IS 13 BP 6245 EP 6248 DI 10.1073/pnas.91.13.6245 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NT461 UT WOS:A1994NT46100105 PM 7517044 ER PT J AU ARANY, Z SELLERS, WR LIVINGSTON, DM ECKNER, R AF ARANY, Z SELLERS, WR LIVINGSTON, DM ECKNER, R TI E1A-ASSOCIATED P300 AND CREB-ASSOCIATED CBP BELONG TO A CONSERVED FAMILY OF COACTIVATORS SO CELL LA English DT Letter ID CYCLIC-AMP; PROTEINS; GENE; PHOSPHORYLATION; TRANSCRIPTION; ACTIVATION C1 HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. RP DANA FARBER CANC INST, BOSTON, MA 02115 USA. NR 13 TC 323 Z9 326 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD JUN 17 PY 1994 VL 77 IS 6 BP 799 EP 800 DI 10.1016/0092-8674(94)90127-9 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NT331 UT WOS:A1994NT33100005 PM 8004670 ER PT J AU CROSSLEY, M ORKIN, SH AF CROSSLEY, M ORKIN, SH TI PHOSPHORYLATION OF THE ERYTHROID TRANSCRIPTION FACTOR GATA-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING ACTIVITY; BETA-GLOBIN LOCUS; CASEIN KINASE-II; PROTEIN-KINASE; GENE-TRANSCRIPTION; CONTROL REGION; HYPERSENSITIVE SITE-3; REGULATORY ELEMENT; MAMMALIAN-CELLS; DISTAL ENHANCER AB GATA-1 is a zinc finger DNA-binding protein thought to be involved in the expression of the vast majority of erythroid specific genes. We have examined the phosphorylation of GATA-1 in murine erythroleukemia (MEL) cells and have mapped the sites of phosphorylation by overexpression of GATA-1 in monkey kidney COS cells. We show that GATA-1 is phosphorylated on 6 serines within its amino terminus in uninduced MEL cells and that a 7th site, serine 310, becomes phosphorylated after MEL cells are induced to differentiate by exposure to dimethyl sulfoxide. This site lies near the carboxyl boundary of the DNA-binding domain in a conserved region of the protein believed to be involved in DNA bending. Detailed analyses indicate, however, that phosphorylation at this site, or the other sites identified, does not significantly influence DNA-binding affinity or specificity, DNA bending, or transcriptional transactivation by GATA-1. C1 CHILDRENS HOSP, DANA FARBER CANC INST, DEPT PEDIAT, DIV HEMATOL ONCOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, HOWARD HUGHES MED INST, BOSTON, MA 02115 USA. RI Crossley, Merlin/D-7888-2011 OI Crossley, Merlin/0000-0003-2057-3642 NR 70 TC 99 Z9 100 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 1994 VL 269 IS 24 BP 16589 EP 16596 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR296 UT WOS:A1994NR29600014 PM 8206977 ER PT J AU MILLER, SR SALO, AL BOGGAN, WO PATRICK, KS AF MILLER, SR SALO, AL BOGGAN, WO PATRICK, KS TI DETERMINATION OF PLASMA COCAINE AND ETHYLCOCAINE (COCAETHYLENE) IN MICE USING GAS-CHROMATOGRAPHY MASS-SPECTROMETRY AND DEUTERATED INTERNAL STANDARDS SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PHASE EXTRACTION COLUMNS; ECGONINE METHYL-ESTER; ETHANOL INGESTION; HUMAN LIVER; METABOLITES; BENZOYLECGONINE; DOPAMINE; SERUM; URINE AB A gas chromatographic-mass spectrometric method is described for the determination of cocaine and ethylcocaine (cocaethylene) from mouse plasma microsamples (50 mu l). [H-2(3)]Cocaine and [H-2(5)]ethylcocaine served as internal standards, analytical separations were performed on a (5% phenyl)methylpolysiloxane capillary column, and detection was by selected-ion monitoring of electron-impact generated fragment ions [M - CO(2)Ph]. Pilot study plasma concentrations of ethylcocaine following coadministration of cocaine and ethanol were less than 5% of the parent drug. C1 MED UNIV S CAROLINA,DEPT PHARMACEUT SCI,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC 29401. FU NIAAA NIH HHS [1RO1AA09487]; NIDA NIH HHS [1RO1DA08034] NR 31 TC 6 Z9 6 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD JUN 17 PY 1994 VL 656 IS 2 BP 335 EP 341 DI 10.1016/0378-4347(94)00133-2 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NW845 UT WOS:A1994NW84500006 PM 7987485 ER PT J AU SINGH, BN AF SINGH, BN TI IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS - NOT THE ULTIMATE GOLD STANDARD FOR GAUGING THERAPY OF VT/FIBRILLATION SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID VENTRICULAR TACHYARRHYTHMIAS; ANTIARRHYTHMIC DRUGS; EFFICACY; LIFE C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90024 USA. RP SINGH, BN (reprint author), W LOS ANGELES VET AFFAIRS MED CTR, DIV CARDIOL 691 111E, WILSHIRE & SAWTELLE BLVD, LOS ANGELES, CA 90073 USA. NR 17 TC 11 Z9 11 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 15 PY 1994 VL 73 IS 16 BP 1211 EP 1213 DI 10.1016/0002-9149(94)90184-8 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NP976 UT WOS:A1994NP97600014 PM 8203341 ER PT J AU DAMICO, DJ MOULTON, RS THEODOSSIADIS, PG YARBOROUGH, JM AF DAMICO, DJ MOULTON, RS THEODOSSIADIS, PG YARBOROUGH, JM TI ERBIUM-YAG LASER PHOTOTHERMAL RETINAL ABLATION IN ENUCLEATED RABBIT EYES SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EXPERIMENTAL VITREOUS MEMBRANES; CARBON-DIOXIDE LASER; ER-YAG; NEODYMIUM-YAG; PHOTOCOAGULATION; SURGERY; ARGON; DIODE; PHOTODECOMPOSITION; IRRADIATION AB The erbium:YAG laser has been shown to produce precise tissue ablation because of the high water absorption of the 2.94-mu m wave-length emitted by this laser. We used an experimental system to create lesions of various depths in the surface of the rabbit retina in enucleated eyes in vitro to examine the potential application to maneuvers such as retinotomy and the removal of epiretinal membranes in vitrectomy. With an air/retinal interface, single pulses produced discrete craters in the retinal surface with a depth proportional to fluence, ranging from 30 mu m for a pulse of 1.3 J/cm(2) to a full-thickness retinotomy at 3.9 J/cm(2). An adjacent zone of coagulated tissue ranging in size from 15 to 40 mu m was noted. Multiple pulses had an additive effect. With a fluid/retinal interface, 20 pulses of 3.6 J/cm(2) produced a full-thickness retinotomy, with an adjacent zone of damaged tissue up to 1 mm, caused by effects of volatilization of intervening fluid. The erbium:YAG laser may have a role in vitreoretinal surgery. C1 COHERENT INC,PALO ALTO,CA. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,LASER RES LAB,BOSTON,MA 02114. RP DAMICO, DJ (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 34 TC 26 Z9 26 U1 0 U2 1 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 JUN 15 PY 1994 VL 117 IS 6 BP 783 EP 790 PG 8 WC Ophthalmology SC Ophthalmology GA NP644 UT WOS:A1994NP64400011 PM 8198163 ER PT J AU OSSWALD, S BROOKS, R ONUNAIN, SS CURWIN, JH ROELKE, M RADVANY, P RUSKIN, JN MCGOVERN, BA AF OSSWALD, S BROOKS, R ONUNAIN, SS CURWIN, JH ROELKE, M RADVANY, P RUSKIN, JN MCGOVERN, BA TI ASYSTOLE AFTER EXERCISE IN HEALTHY-PERSONS SO ANNALS OF INTERNAL MEDICINE LA English DT Note ID ORGANIC HEART-DISEASE; UP TILT; HYPOTENSION-BRADYCARDIA; CARDIAC ASYSTOLE; SYNCOPE C1 MASSACHUSETTS GEN HOSP,CARDIAC ARRHYTHMIA SERV,BOSTON,MA 02114. ST PETERS HOSP,ALBANY,NY. NR 19 TC 23 Z9 24 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 15 PY 1994 VL 120 IS 12 BP 1008 EP 1011 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NQ964 UT WOS:A1994NQ96400007 PM 8185132 ER PT J AU TAKAHASHI, R HEYDARI, AR GUTSMANN, A SABIA, M RICHARDSON, A AF TAKAHASHI, R HEYDARI, AR GUTSMANN, A SABIA, M RICHARDSON, A TI THE HEAT-SHOCK TRANSCRIPTION FACTOR IN LIVER EXISTS IN A FORM THAT HAS DNA-BINDING ACTIVITY BUT NO TRANSCRIPTIONAL ACTIVITY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN; ACTIVATION; PROMOTER; YEAST; AGE; OLIGOMERIZATION; HEPATOCYTES; STRESS; GENES; CELLS AB The binding activity of the heat shock transcription factor (HSF) to the heat shock element (HSE) is observed in non-stressed Liver and freshly isolated hepatocytes when the expression of hsp70 is undetectable, HSF binding activity in non-stressed liver/hepatocytes is specific for HSE and similar to the HSF binding activity observed in heat shocked hepatocytes that is associated with hsp70 transcription. However, the HSF binding activity in non-stressed and heat shock cells can be distinguished on the basis of the thermal stability in vitro. The HSE binding activity of cell extracts isolated from non-stressed liver/hepatocytes was lost rapidly when the extracts were incubated at 37 degrees C. In contrast, the HSF binding activity of cell extracts isolated from heat shocked hepatocytes was relatively stable at 37 degrees C. Based on our observations, we propose that the activation of HSF is a multistep process that involves a change in conformation after oligomerization and the acquisition of DNA binding to a form that is more thermostable and is associated with increased hsp70 transcription. (C) 1994 Academic Press, Inc. C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GERIATR & GERONTOL,SAN ANTONIO,TX 78284. TOHO UNIV,SCH PHARMACEUT SCI,CHIBA 274,JAPAN. FU NIA NIH HHS [AG01548]; NIEHS NIH HHS [ES06277] NR 19 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 1994 VL 201 IS 2 BP 552 EP 558 DI 10.1006/bbrc.1994.1737 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NQ805 UT WOS:A1994NQ80500010 PM 8002986 ER PT J AU STONE, RM AF STONE, RM TI MYELODYSPLASTIC SYNDROME AFTER AUTOLOGOUS TRANSPLANTATION FOR LYMPHOMA - THE PRICE OF PROGRESS SO BLOOD LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; INTERMEDIATE-GRADE; THERAPY; SECONDARY; LEUKEMIA; DISEASE; RISK; CHEMOTHERAPY; REMISSION RP STONE, RM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 23 TC 84 Z9 84 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 JUN 15 PY 1994 VL 83 IS 12 BP 3437 EP 3440 PG 4 WC Hematology SC Hematology GA NR905 UT WOS:A1994NR90500002 PM 8204870 ER PT J AU DVORAK, AM TEPPER, RI WELLER, PF MORGAN, ES ESTRELLA, P MONAHANEARLEY, RA GALLI, SJ AF DVORAK, AM TEPPER, RI WELLER, PF MORGAN, ES ESTRELLA, P MONAHANEARLEY, RA GALLI, SJ TI PIECEMEAL DEGRANULATION OF MAST-CELLS IN THE INFLAMMATORY EYELID LESIONS OF INTERLEUKIN-4 TRANSGENIC MICE - EVIDENCE OF MAST-CELL HISTAMINE-RELEASE IN-VIVO BY DIAMINE OXIDASE-GOLD ENZYME-AFFINITY ULTRASTRUCTURAL CYTOCHEMISTRY SO BLOOD LA English DT Article ID STIMULATORY FACTOR-I; VASCULAR-PERMEABILITY FACTOR; C-KIT RECEPTOR; CROHNS-DISEASE; VERNAL CONJUNCTIVITIS; BASOPHILIC LEUKOCYTES; BONE-MARROW; T-CELLS; INVIVO; LYMPHOKINE C1 BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. RP DVORAK, AM (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI-23990, AI-22674, AI-33372] NR 50 TC 78 Z9 79 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 JUN 15 PY 1994 VL 83 IS 12 BP 3600 EP 3612 PG 13 WC Hematology SC Hematology GA NR905 UT WOS:A1994NR90500023 PM 7515717 ER PT J AU GRIBBEN, JG NEUBERG, D BARBER, M MOORE, J PESEK, KW FREEDMAN, AS NADLER, LW AF GRIBBEN, JG NEUBERG, D BARBER, M MOORE, J PESEK, KW FREEDMAN, AS NADLER, LW TI DETECTION OF RESIDUAL LYMPHOMA-CELLS BY POLYMERASE CHAIN-REACTION IN PERIPHERAL-BLOOD IS SIGNIFICANTLY LESS PREDICTIVE FOR RELAPSE THAN DETECTION IN BONE-MARROW SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; STAGE FOLLICULAR LYMPHOMA; T(14-18); TRANSPLANTATION; TRANSLOCATION; AMPLIFICATION; BREAKPOINT; DISEASE; REARRANGEMENT; REMISSION RP GRIBBEN, JG (reprint author), DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES,44 BINNEY ST,BOSTON,MA 02215, USA. FU FIC NIH HHS [FO5-TWO44]; NCI NIH HHS [CA-55207, CA-34183] NR 33 TC 154 Z9 156 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 JUN 15 PY 1994 VL 83 IS 12 BP 3800 EP 3807 PG 8 WC Hematology SC Hematology GA NR905 UT WOS:A1994NR90500045 PM 8204898 ER PT J AU WEN, PY ALEXANDER, E BLACK, PM FINE, HA RIESE, N LEVIN, JM COLEMAN, CN LOEFFLER, JS AF WEN, PY ALEXANDER, E BLACK, PM FINE, HA RIESE, N LEVIN, JM COLEMAN, CN LOEFFLER, JS TI LONG-TERM RESULTS OF STEREOTAXIC BRACHYTHERAPY USED IN THE INITIAL TREATMENT OF PATIENTS WITH GLIOBLASTOMAS SO CANCER LA English DT Article DE BRAIN NEOPLASM; GLIOBLASTOMA; BRACHYTHERAPY; COMPLICATIONS; SURVIVAL ID MALIGNANT BRAIN-TUMORS; ACTIVITY I-125 SOURCES; INTERSTITIAL BRACHYTHERAPY; RADIATION-THERAPY; ANAPLASTIC ASTROCYTOMA; FINAL REPORT; GLIOMAS; SURVIVAL; RADIOTHERAPY; IMPLANTATION AB Background. Despite optimal therapy with surgery and radiotherapy, the prognosis of patients with glioblastomas remains poor. Stereotactic brachytherapy involves the accurate placement of radioactive isotopes within brain tumors, significantly increasing the dose of radiation that can be delivered to the tumor bed without substantial risk to surrounding normal tissue, potentially improving local tumor control and patient survival. Methods. Between February 1987 and July 1993, the authors treated 56 patients with glioblastomas with stereotactic brachytherapy as part of their initial therapy. Patients underwent surgery, limited field external beam radiotherapy, and brachytherapy with temporary high-activity iodine 125 sources, giving an additional 50 Gy to the tumor bed. Results. Median survival for patients undergoing brachytherapy was 18 months compared with 11 months for a matched brachytherapy control group with similar clinical and radiologic features (P < 0.0007). Survival rates at 1, 2, and 3 years after diagnosis of 83%, 34%, and 27%, respectively, for patients receiving brachytherapy were significantly increased compared with survival rates of 40%, 12.5%, and 9%, respectively, for control subjects. Thirty-six patients (64%) underwent reoperation for symptomatic radiation necrosis from 3 to 42 months (median, 11 months) after brachytherapy. The median survival of patients undergoing reoperation was 22 months compared with 13 months for those who did not have further surgery (P < 0.02). Thirty-five percent of patients relapsed locally within the brachytherapy target volume, whereas 65% had marginal or distant relapses. C1 BRIGHAM & WOMENS HOSP,CHILDRENS HOSP,CTR BRAIN TUMOR,DANA FARBER CANC INST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. FU NCI NIH HHS [K11CAO1467, R01 CA-42391, K11CAO1496] NR 43 TC 95 Z9 96 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 JUN 15 PY 1994 VL 73 IS 12 BP 3029 EP 3036 DI 10.1002/1097-0142(19940615)73:12<3029::AID-CNCR2820731222>3.0.CO;2-4 PG 8 WC Oncology SC Oncology GA NQ408 UT WOS:A1994NQ40800021 PM 8200000 ER PT J AU VANLEEUWEN, RL DEKKER, SK ARBISER, JL VERMEER, BJ BRUIJN, JA BYERS, HR AF VANLEEUWEN, RL DEKKER, SK ARBISER, JL VERMEER, BJ BRUIJN, JA BYERS, HR TI PHORBOL ESTER-INDUCED RAPID ATTACHMENT AND SPREADING OF MELANOMA-CELLS AND THE ROLE OF EXTRACELLULAR-MATRIX PROTEINS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID KINASE-C; CALPHOSTIN-C; ADHESION; FIBRONECTIN; METASTASIS; ACTIVATION; INTEGRINS; INHIBITION; ONCOGENES; LAMININ AB Phorbol 12-myristate 13-acetate (PMA) is a tumour promotor that acts as a potent protein kinase C (PKC) activator that has significant effects on tumour cell attachment and spreading. We tested whether these effects of PMA may be observed in human melanoma cells, and whether a specific response to extracellular matrix proteins may be mediated by shifts in the expression of beta(1) integrins. We used cell attachment assays, video time lapse cell spreading assays, flow cytometry, function blocking monoclonal antibodies (MAbs) and PKC inhibitor Calphostin C to address these questions. We established that PMA induces a rapid and temporary enhancement of cell attachment and spreading which was not accompanied by a significant change in the expression of beta(1) integrins. Spreading of melanoma cells that were not stimulated with PMA could be significantly blockedd with a function blocking MAb (clone P4C10) against the common beta(1) integrin subunit. The spreading and attachment of the PMA treated cells was also significantly reduced, but less so, after MAb treatment. The PMA enhanced cell attachment and spreading could be effectively blocked by RGD sequences and PKC inhibitor. Taken together, our data indicate that PMA induces a rapid and temporary ECM-dependent enhancement of melanoma cell attachement and spreading, and that the respone to ECM components appears not to be due to significant shifts in beta(1) integrin expression, but rather to activation of beta(1) integrins. (C) 1994 Wiley-Liss, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA. LEIDEN UNIV,DEPT DERMATOL,LEIDEN,NETHERLANDS. LEIDEN UNIV,DEPT PATHOL,LEIDEN,NETHERLANDS. FU NCI NIH HHS [CA-45587] NR 23 TC 23 Z9 23 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 1994 VL 57 IS 6 BP 894 EP 900 DI 10.1002/ijc.2910570620 PG 7 WC Oncology SC Oncology GA NR234 UT WOS:A1994NR23400019 PM 7515859 ER PT J AU TEICHER, BA HOLDEN, SA ARA, G SOTOMAYOR, EA HUANG, ZD CHEN, YN BREM, H AF TEICHER, BA HOLDEN, SA ARA, G SOTOMAYOR, EA HUANG, ZD CHEN, YN BREM, H TI POTENTIATION OF CYTOTOXIC CANCER THERAPIES BY TNP-470 ALONE AND WITH OTHER ANTI-ANGIOGENIC AGENTS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MELPHALAN ANTITUMOR-ACTIVITY; INHIBITOR TNP-470; FLUOSOL-DA; INVIVO; CHEMOTHERAPY; MINOCYCLINE; ENHANCEMENT; METASTASIS; RADIATION; CARCINOMA AB The ability of TNP-470, a synthetic analog of fumagillin which has been described as an anti-angiogenic agent, to potentiate cytotoxic cancer therapies was investigated in vivo in the murine FSallC fibrosarcoma and the Lewis lung carcinoma. TNP-470 was more toxic toward FSallC tumor cells from tumors treated in vivo than toward bone-marrow CFU-GM from the same animals. TNP-470 had a dose-modifying effect on the toxicity of cyclophosphamide toward FSallC tumor cells which amounted to an 8-fold increase in tumor-cell killing at a cyclophosphamide does of 500 mg/kg. Treatment with TNP-470 and minocycline increased the permeability of the FSall fibrosarcoma in vivo to the fluorescent dye Hoechst 33342 and increased the killing of both the brignt and the dim tumor cells by cyclophophamide. TNP-470, especially in combination with minocycline, formed a highly effective modulator combination for treatment of the Lewis lung carcinoma with cytotoxic cancer therapies against primary and metastatic disease. The combination of TNP-470/minocycyline and cyclophosphamide led to 40 to 50% long-term survivors in Lewis-lung-carcinoma-bearing animals. Our results indicate that the use of anti-angiogenic modulators in cancer therapy is a very promising area for further study. (C) 1994 Wiley-Liss, Inc. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP TEICHER, BA (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01-CA38493, P01-CA19589, R01-CA50174] NR 25 TC 196 Z9 204 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 1994 VL 57 IS 6 BP 920 EP 925 DI 10.1002/ijc.2910570624 PG 6 WC Oncology SC Oncology GA NR234 UT WOS:A1994NR23400023 PM 7515861 ER PT J AU BUSWELL, L RECHT, A CLARK, J RAVIKUMAR, T BUSSE, PM COLEMAN, CN AF BUSWELL, L RECHT, A CLARK, J RAVIKUMAR, T BUSSE, PM COLEMAN, CN TI COMBINED-MODALITY THERAPY OF ESOPHAGEAL CANCER WITH RADIOTHERAPY, ETANIDAZOLE, AND CISPLATIN-FLUOROURACIL, WITH OR WITHOUT SURGERY - NEUROTOXICITY, OTHER TOXICITIES AND OUTCOME SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 8th International Conference on Chemical Modifiers of Cancer Treatment CY JUN 16-19, 1993 CL KYOTO, JAPAN SP BRISTOL MYERS SQUIBB CO, DAIICHI PHARM CO LTD, DAIKIN IND LTD, EISAI CO LTD, HLTH RES FDN, JAPAN CLIN LABS, JAPAN RADIOSENTIZAT RES ASSOC, NIHON SCHERING K K, OSAKA PHARM MANUFACTURERS ASSOC, POLA CHEM IND INC, ROBERTS PHARM, SHIMAZU SCI FDN, STERLING WINTHROP CORP, PHARM MANUFACTURERS ASSOC TOKYO, UEHARA MEM FDN, US BIOSCI CORP, YAMANOUCHI MED CO LTD, ZERIA PHARM CO LTD DE ETANIDAZOLE; PHARMACOKINETICS; RADIATION SENSITIZERS; 2-NITROMIDAZOLES; NEUROTOXICITY; PERIPHERAL NEUROPATHY ID CELL RADIOSENSITIZER SR-2508; PHASE-I TRIAL; RADIATION-THERAPY; HYPERBARIC-OXYGEN; CARCINOMA; CHEMOTHERAPY; NEUROPATHY AB Purpose: To investigate whether etanidazole and cisplatin can be given safely together and to evaluate the relationship between incidence of peripheral neuropathy and cumulative exposure to etanidazole and cisplatin, as well as other toxicities and treatment outcome. Methods and Materials: Thirty-two previously untreated patients with locally advanced esophageal cancer were entered on a Phase I study of etanidazole combined with radiation therapy and chemotherapy. Cisplatin/5-FU (two cycles, weeks 1 and 4) and etanidazole (weeks 2, 3 and 5) were given concurrently with radiation therapy. Eligible patients then underwent surgical resection. All patients were scheduled to receive two additional cycles of cisplatin/ 5-FU chemotherapy after completion of radiation therapy (definitive arm) or surgery (preoperative arm). Results: Of 19 fully evaluable patients, nine (47%) developed peripheral neuropathy. Six of six patients, 65 years or older, experienced peripheral neuropathy, compared with three of 13 patients less than 65 years old (p = .003). For patients younger than 65 years, two of the two patients with single dose area under the curve (AUC) > 4.0 mMhr experienced peripheral neuropathy, compared with one of 11 patients with single-dose AUC < 4.0 mMhr (p = .03). Grade 4 toxicity included neutropenia (23%) and thrombocytopenia (26%). No other Grade 4 toxicity was observed. The pathologic complete response rate in patients who underwent surgical resection was 29%. Conclusion: This regime of chemotherapy, radiotherapy, and etanidazole had acceptable toxicity. However, combining etanidazole and cisplatin appears to increase the risk of developing peripheral neuropathy for at least some categories of patients. Further studies of these interactions are needed. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT SURG,NEW HAVEN,CT 06510. FU NCI NIH HHS [CA 42391] NR 25 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 15 PY 1994 VL 29 IS 3 BP 535 EP 540 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NQ843 UT WOS:A1994NQ84300022 PM 8005812 ER PT J AU SHULMAN, LN BUSWELL, L KALISH, LA COLEMAN, CN AF SHULMAN, LN BUSWELL, L KALISH, LA COLEMAN, CN TI USE OF THE HYPOXIC CELL SENSITIZER ETANIDAZOLE (SR-2508) WITH INTRAVENOUS MELPHALAN AND PREDNISONE IN THE TREATMENT OF MULTIPLE-MYELOMA - A PHARMACOKINETIC STUDY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 8th International Conference on Chemical Modifiers of Cancer Treatment CY JUN 16-19, 1993 CL KYOTO, JAPAN SP BRISTOL MYERS SQUIBB CO, DAIICHI PHARM CO LTD, DAIKIN IND LTD, EISAI CO LTD, HLTH RES FDN, JAPAN CLIN LABS, JAPAN RADIOSENTIZAT RES ASSOC, NIHON SCHERING K K, OSAKA PHARM MANUFACTURERS ASSOC, POLA CHEM IND INC, ROBERTS PHARM, SHIMAZU SCI FDN, STERLING WINTHROP CORP, PHARM MANUFACTURERS ASSOC TOKYO, UEHARA MEM FDN, US BIOSCI CORP, YAMANOUCHI MED CO LTD, ZERIA PHARM CO LTD DE ETANIDAZOLE; HYPOXIC CELL SENSITIZER; MELPHALAN; MULTIPLE MYELOMA ID MISONIDAZOLE; CHEMOSENSITIZATION; CANCER; TRIAL AB Purpose: A study was undertaken adding the alkylating agent sensitizer etanidazole to intravenous melphalan and oral prednisone for patients with multiple myeloma. This study explored the toxicity profile of these agents when given together and assessed the ability to attain adequate serum levels of etanidazole to permit sensitization to occur. Methods and Materials: Etanidazole was administered intravenously in two doses of 3 g/m(2) and 5 g/m(2) 90 min apart immediately prior to the administration of intravenous melphalan and oral prednisone for three consecutive cycles (total dose 24 g/m(2)). Patients received three additional cycles without etanidazole, allowing a comparison of hematologic toxicity from melphalan with and without etanidazole. Results: Hematologic toxicity was moderate (Grade 3 or 4), but severity was similar during cycles with and without etanidazole. Only one patient developed a Grade 1 peripheral neuropathy questionably related to etanidazole, Most patients had etanidazole levels of greater than or equal to 70 ug/ml for 7 h, a level felt to be necessary for sensitization to occur. Conclusion: Etanidazole, administered as described, results in adequate serum levels for potential alkylating agent sensitization, without significant toxicity. C1 JOINT CTR RADIAT ONCOL,BOSTON,MA. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP SHULMAN, LN (reprint author), BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 42391] NR 12 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 15 PY 1994 VL 29 IS 3 BP 541 EP 543 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NQ843 UT WOS:A1994NQ84300023 PM 8005813 ER PT J AU SHULMAN, LN GOODMAN, H BUSWELL, L MUTO, M BERKOWITZ, R TEICHER, B KUSUMOTO, T HURWITZ, SJ KALISH, LA COLEMAN, CN AF SHULMAN, LN GOODMAN, H BUSWELL, L MUTO, M BERKOWITZ, R TEICHER, B KUSUMOTO, T HURWITZ, SJ KALISH, LA COLEMAN, CN TI PHASE-I PHARMACOKINETIC STUDY OF THE HYPOXIC CELL SENSITIZER ETANIDAZOLE WITH CARBOPLATIN AND CYCLOPHOSPHAMIDE IN THE TREATMENT OF ADVANCED OVARIAN-CANCER SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 8th International Conference on Chemical Modifiers of Cancer Treatment CY JUN 16-19, 1993 CL KYOTO, JAPAN SP BRISTOL MYERS SQUIBB CO, DAIICHI PHARM CO LTD, DAIKIN IND LTD, EISAI CO LTD, HLTH RES FDN, JAPAN CLIN LABS, JAPAN RADIOSENTIZAT RES ASSOC, NIHON SCHERING K K, OSAKA PHARM MANUFACTURERS ASSOC, POLA CHEM IND INC, ROBERTS PHARM, SHIMAZU SCI FDN, STERLING WINTHROP CORP, PHARM MANUFACTURERS ASSOC TOKYO, UEHARA MEM FDN, US BIOSCI CORP, YAMANOUCHI MED CO LTD, ZERIA PHARM CO LTD DE ETANIDAZOLE; CARBOPLATIN; CYCLOPHOSPHAMIDE; HYPOXIC CELL SENSITIZER; OVARIAN CANCER ID RADIOSENSITIZER SR-2508; MISONIDAZOLE; MELPHALAN; TRIAL; CHEMOSENSITIZATION; RADIATION; CISPLATIN AB Purpose: A Phase I study was undertaken to determine the maximum tolerated dose of the hypoxic cell sensitizer etanidazole which could be administered with carboplatin and cyclophosphamide, to determine whether adequate serum levels of etanidazole were achieved to allow for alkylating agent sensitization, and whether pretreatment with etanidazole altered carboplatin pharmacokinetics. Methods and Materials: Patients received 2 g/m(2) of intravenous etanidazole followed by a second dose of 4 g/m(2) 90 min later, followed by intravenous carboplatin (300 mg/m(2)) and cyclophosphamide (600 mg/m(2)) for four treatment cycles. Patients received an additional two cycles of carboplatin and cyclophosphamide without etanidazole. Results: Two patients who received a total of 24 g/m(2) of etanidazole developed Grade 1 neurotoxicity, and therefore etanidazole doses were not escalated further. The grade of granulocytopenia was worse after cycles with etanidazole than after those without (p = 0.03), but clinical outcome was not different. Etanidazole levels were adequate for alkylating agent sensitization (> 70 ug/ml) in all patients for the majority of the 7 h of testing. Pharmacokinetic data suggested t(1/2 alpha), and t(1/2 beta) for carboplatin were prolonged after pretreatment with etanidazole. Conclusion: Etanidazole, 2 g/m(2) followed by 4 g/m(2) 90 min later, is safe and results in adequate serum levels for alkylating agent sensitization. Neurotoxicity appears to prevent dose escalation of etanidazole, and an interaction between etanidazole and carboplatin may have enhanced neurotoxicity in these patients. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV GYNECOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. RP SHULMAN, LN (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV HEMATOL ONCOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 42391] NR 14 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUN 15 PY 1994 VL 29 IS 3 BP 545 EP 548 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NQ843 UT WOS:A1994NQ84300024 PM 8005814 ER PT J AU COHEN, LS FRIEDMAN, JM JEFFERSON, JW JOHNSON, EM WEINER, ML AF COHEN, LS FRIEDMAN, JM JEFFERSON, JW JOHNSON, EM WEINER, ML TI THE RISK OF IN-UTERO EXPOSURE TO LITHIUM - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID PREGNANCY RP COHEN, LS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA, USA. NR 5 TC 0 Z9 0 U1 0 U2 1 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 JUN 15 PY 1994 VL 271 IS 23 BP 1828 EP 1829 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NP959 UT WOS:A1994NP95900020 ER PT J AU FISHER, CJ DHAINAUT, JFA OPAL, SM PRIBBLE, JP BALK, RA SLOTMAN, GJ IBERTI, TJ RACKOW, EC SHAPIRO, MJ GREENMAN, RL REINES, HD SHELLY, MP THOMPSON, BW LABRECQUE, JF CATALANO, MA KNAUS, WA SADOFF, JC ASTIZ, M CARPATI, C BONE, RC FREIDMAN, B MURE, AJ BRATHWAITE, C SHAPIRO, E MELHORN, L TAYLOR, R KEEGAN, M OBRIEN, J SCHEIN, R PENA, M WASSERLOUF, M OROPELLO, J BENJAMIN, E DELGUIDICE, R EMMANUEL, G LIE, T ANDERSON, L MARSHALL, J DEMAJO, W ROTSTEIN, O FOSTER, D ABRAHAM, E MIDDLETON, H PERRY, C LEVY, H FRY, DE SIMPSON, SQ CROWELL, RE NEIDHART, M STEVENS, D COFFMAN, T NARASIMHAM, N MERRICK, DK BERGQUIST, W MATZEL, KE HUEBLER, M FOULKE, GE ALBERTSON, TE WALBY, WF ALLEN, RP BAUGHMAN, R HASSELGREN, PO FINK, MP FAVORITO, F THOMPSON, BT CORBIN, R SHELLHORSE, GY FRAZIER, A WHITE, S GARRARD, C ACOURT, C STORER, S GERVICH, DH FOSHE, D BRASE, R BAGDAHN, A COONEY, R SMITH, JS MARTIN, LF VINCENT, JL FRIEDMAN, G BERLOT, G FLETCHER, JR WILLIAMS, MD WRIGHT, TF JOHNSON, S FEILD, C WOLF, K MACINTYRE, N DUBIN, HG DURKIN, MR DUBIN, PK STAUBACH, KH FEIN, AM SCHULMAN, DB NIEDERMAN, MS CHALFIN, DB VANLEEUWEN, PAM BOERMEESTER, MA SCHNEIDER, AJ BANDER, J IMM, A BERNARD, G NELSON, L STROUD, M SAFCSAK, K CERRA, F RINDAL, J MANN, H HALPERN, N SILVERSTEIN, J ALICEA, M SIBBALD, WJ MARTIN, CM RUTLEDGE, FS PETTI, K RUSSELL, JA KRUGER, R DRUMMOND, A LANGE, P SEIFERT, T DUROCHER, A TENAILLON, A BOITEAU, R LHERM, T LOWRY, SF COYLE, SM BARIE, PS DEMARIA, E SNYDMAN, DR SCHWAITZBERG, SD NASRAWAY, SA GRINDLINGER, J SUMMER, W DEBOISBLANC, B WAHL, M ALESTIG, K GROSSMAN, J MAKI, D PAZ, HL WEINER, M BIHARI, D CAMPBELL, D BLEICHNER, G DAHN, MS LANGE, MPA HALL, J POHLMAN, A WENZEL, RP GROSSERODE, M COSTIGAN, M MILESKI, W WEIGELT, J YESTON, N IRIZARRY, C ROSS, J ROBBINS, J NIGHTINGALE, P OWEN, K SANDSTEDT, S BERG, S SIMON, GL SENEFF, MG CONRY, KM ZIMMERMAN, JL DELLINGER, RP JOHNSTON, R ALLEE, P GRANDE, PO MYHRE, E DHAINAUT, JF HAMY, I MIRA, JP HARMON, J WHITE, J MCKIE, L SILVERMAN, H TUMA, P BENNETT, D PORTER, JC LAURELL, MH JACOBS, S ASH, S STILES, DM PRIOR, MJ KNATTERUD, G TERRIN, M KUFERA, J WILKENS, P RA, K MONROE, L SPRUNG, C HAMILTON, CM MATTHAY, R MCCABE, W TONASCIA, J WIEDEMAN, H WITTES, J CAMPION, GV CROFT, CR LUSTICK, R LOOKABAUGH, J GORDON, GS NOE, L BLOEDOW, D SMITH, CG BRANNON, D KUSH, R NG, D MOORE, E BAZEMORE, K GALVAN, M WAGNER, D HARRELL, F STABLEIN, D AF FISHER, CJ DHAINAUT, JFA OPAL, SM PRIBBLE, JP BALK, RA SLOTMAN, GJ IBERTI, TJ RACKOW, EC SHAPIRO, MJ GREENMAN, RL REINES, HD SHELLY, MP THOMPSON, BW LABRECQUE, JF CATALANO, MA KNAUS, WA SADOFF, JC ASTIZ, M CARPATI, C BONE, RC FREIDMAN, B MURE, AJ BRATHWAITE, C SHAPIRO, E MELHORN, L TAYLOR, R KEEGAN, M OBRIEN, J SCHEIN, R PENA, M WASSERLOUF, M OROPELLO, J BENJAMIN, E DELGUIDICE, R EMMANUEL, G LIE, T ANDERSON, L MARSHALL, J DEMAJO, W ROTSTEIN, O FOSTER, D ABRAHAM, E MIDDLETON, H PERRY, C LEVY, H FRY, DE SIMPSON, SQ CROWELL, RE NEIDHART, M STEVENS, D COFFMAN, T NARASIMHAM, N MERRICK, DK BERGQUIST, W MATZEL, KE HUEBLER, M FOULKE, GE ALBERTSON, TE WALBY, WF ALLEN, RP BAUGHMAN, R HASSELGREN, PO FINK, MP FAVORITO, F THOMPSON, BT CORBIN, R SHELLHORSE, GY FRAZIER, A WHITE, S GARRARD, C ACOURT, C STORER, S GERVICH, DH FOSHE, D BRASE, R BAGDAHN, A COONEY, R SMITH, JS MARTIN, LF VINCENT, JL FRIEDMAN, G BERLOT, G FLETCHER, JR WILLIAMS, MD WRIGHT, TF JOHNSON, S FEILD, C WOLF, K MACINTYRE, N DUBIN, HG DURKIN, MR DUBIN, PK STAUBACH, KH FEIN, AM SCHULMAN, DB NIEDERMAN, MS CHALFIN, DB VANLEEUWEN, PAM BOERMEESTER, MA SCHNEIDER, AJ BANDER, J IMM, A BERNARD, G NELSON, L STROUD, M SAFCSAK, K CERRA, F RINDAL, J MANN, H HALPERN, N SILVERSTEIN, J ALICEA, M SIBBALD, WJ MARTIN, CM RUTLEDGE, FS PETTI, K RUSSELL, JA KRUGER, R DRUMMOND, A LANGE, P SEIFERT, T DUROCHER, A TENAILLON, A BOITEAU, R LHERM, T LOWRY, SF COYLE, SM BARIE, PS DEMARIA, E SNYDMAN, DR SCHWAITZBERG, SD NASRAWAY, SA GRINDLINGER, J SUMMER, W DEBOISBLANC, B WAHL, M ALESTIG, K GROSSMAN, J MAKI, D PAZ, HL WEINER, M BIHARI, D CAMPBELL, D BLEICHNER, G DAHN, MS LANGE, MPA HALL, J POHLMAN, A WENZEL, RP GROSSERODE, M COSTIGAN, M MILESKI, W WEIGELT, J YESTON, N IRIZARRY, C ROSS, J ROBBINS, J NIGHTINGALE, P OWEN, K SANDSTEDT, S BERG, S SIMON, GL SENEFF, MG CONRY, KM ZIMMERMAN, JL DELLINGER, RP JOHNSTON, R ALLEE, P GRANDE, PO MYHRE, E DHAINAUT, JF HAMY, I MIRA, JP HARMON, J WHITE, J MCKIE, L SILVERMAN, H TUMA, P BENNETT, D PORTER, JC LAURELL, MH JACOBS, S ASH, S STILES, DM PRIOR, MJ KNATTERUD, G TERRIN, M KUFERA, J WILKENS, P RA, K MONROE, L SPRUNG, C HAMILTON, CM MATTHAY, R MCCABE, W TONASCIA, J WIEDEMAN, H WITTES, J CAMPION, GV CROFT, CR LUSTICK, R LOOKABAUGH, J GORDON, GS NOE, L BLOEDOW, D SMITH, CG BRANNON, D KUSH, R NG, D MOORE, E BAZEMORE, K GALVAN, M WAGNER, D HARRELL, F STABLEIN, D TI RECOMBINANT HUMAN INTERLEUKIN-1 RECEPTOR ANTAGONIST IN THE TREATMENT OF PATIENTS WITH SEPSIS SYNDROME - RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; SEPTIC SHOCK; SUBLETHAL ENDOTOXEMIA; MONOCLONAL-ANTIBODY; IL-1 RECEPTOR; MORTALITY; CACHECTIN; RABBITS; PATHOGENESIS; BACTEREMIA AB Objective.-To further define the safety and efficacy of recombinant human interleukin 1 receptor antagonist (rhlL-1ra) in the treatment of sepsis syndrome. Study Design.-Randomized, double-blind, placebo-controlled, multicenter, multinational clinical trial. Population.-A total of 893 patients with sepsis syndrome received an intravenous loading dose of rhIL-1ra, 100 mg, or placebo followed by a continuous 72-hour intravenous infusion of rhIL-1ra (1.0 or 2.0 mg/kg per hour) or placebo. Outcome Measure.-Twenty-eight-day all-cause mortality. Results.-There was not a significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication (n=893; generalized Wilcoxon statistic, P=.22) or among patients with shock at study entry (n=713; generalized Wilcoxon statistic, P=.23), the two primary efficacy analyses specified a priori for this trial. Results from secondary analyses suggest an increase in survival time with rhIL-1ra treatment among patients with dysfunction of one or more organs (n=563; linear dose-response, P=.009). Retrospective analysis demonstrated an increase In survival time with rhIL-1ra treatment among patients with a predicted risk of mortality of 24% or greater (n=580; linear dose-response, P=.005) as well as among patients with both dysfunction of one or more organs and a predicted risk of mortality of 24% or greater (n=411; linear dose-response, P=.002). Conclusions.-There was not a statistically significant increase in survival time for rhIL-1ra treatment compared with placebo among all patients who received the study medication or among patients with shock at study entry. Secondary and retrospective analyses of efficacy suggest that treatment with rhIL-1ra results in a dose-related increase in survival time among patients with sepsis who have organ dysfunction and/or a predicted risk of mortality of 24% or greater. C1 UNIV PARIS 05,COCHIN PORT ROYAL HOSP,DEPT INTENS CARE MED,PARIS,FRANCE. BROWN UNIV,SCH MED,DEPT MED,PROVIDENCE,RI 02912. SYNERGEN INC,DEPT CLIN RES,BOULDER,CO. RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT MED,CHICAGO,IL 60612. UNIV MED & DENT NEW JERSEY,COOPER HOSP,DEPT SURG,CAMDEN,NJ 08103. MT SINAI MED CTR,DEPT SURG,NEW YORK,NY 10029. ST VINCENTS HOSP & MED CTR,DEPT MED,NEW YORK,NY 10011. ST LOUIS UNIV,MED CTR,DEPT SURG,ST LOUIS,MO 63110. VET AFFAIRS MED CTR,DEPT MED,MIAMI,FL. UNIV MIAMI,SCH MED,MIAMI,FL. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT SURG,RICHMOND,VA 23298. UNIV S MANCHESTER HOSP,INTENS CARE UNIT,MANCHESTER,LANCS,ENGLAND. MARYLAND MED RES INST,BALTIMORE,MD. GEORGE WASHINGTON UNIV,MED CTR,INTENS CARE RES UNIT,WASHINGTON,DC 20037. USA,WALTER REED ARMY INST RES,DIV COMMUN DIS & IMMUNOL,WASHINGTON,DC. ST LOUIS HLTH SCI CTR,ST LOUIS,MO. VET AFFAIRS MED CTR,BAY PINES,FL. UNIV S FLORIDA,TAMPA,FL. TORONTO GEN HOSP,TORONTO,ON,CANADA. UNIV NEW MEXICO,MED CTR,ALBUQUERQUE,NM 87131. VET AFFAIRS MED CTR,BOISE,ID. ST LUKES REG MED CTR,BOISE,ID. ST ALPHONSUS REG MED CTR,BOISE,ID. UNIV ERLANGEN NURNBERG,CHIRURG KLIN,W-8520 ERLANGEN,GERMANY. CALIF STATE UNIV SACRAMENTO,DAVIS MED CTR,SACRAMENTO,CA. UNIV CINCINNATI,MED CTR,CINCINNATI,OH 45267. MASSACHUSETTS GEN HOSP,BOSTON,MA. CAROLINAS MED CTR,CHARLOTTE,NC. JOHN RADCLIFFE HOSP,OXFORD,ENGLAND. CRIT CARE ASSOCIATES,DES MOINES,IA. ZENT KRANKENHAUS LINKS WESER,BREMEN,GERMANY. PENN STATE UNIV,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033. FREE UNIV BRUSSELS,HOP ERASME,B-1070 BRUSSELS,BELGIUM. UNIV SO ALABAMA,MED CTR,MOBILE,AL. UNIV KENTUCKY,ALBERT B CHANDLER MED CTR,LEXINGTON,KY 40536. DUKE UNIV,MED CTR,DURHAM,NC. UNIV LUBECK,LUBECK,GERMANY. WINTHROP UNIV HOSP,MINEOLA,NY. FREE UNIV AMSTERDAM HOSP,AMSTERDAM,NETHERLANDS. WAYNE STATE UNIV,HARPER HOSP,DETROIT,MI. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37212. UNIV MINNESOTA,SCH MED,MINNEAPOLIS,MN. VET AFFAIRS MED CTR,BRONX,NY. VICTORIA HOSP,LONDON,ON,CANADA. ST PAULS HOSP,VANCOUVER,BC,CANADA. HOP CALMETTE,LILLE,FRANCE. HOP LOUISE MICHEL,EVRY,FRANCE. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA. GOTHENBURG UNIV,GOTHENBURG,SWEDEN. UNIV WISCONSIN,SCH MED,MADISON,WI. HAHNEMANN UNIV,PHILADELPHIA,PA. GUYS HOSP,LONDON,ENGLAND. CTR HOSP ARGENTEUIL,ARGENTEUIL,FRANCE. UNIV DETROIT,CTR HLTH,DETROIT,MI. UNIV CHICAGO,CHICAGO,IL. UNIV IOWA HOSP & CLIN,IOWA CITY,IA. UNIV TEXAS,SW MED CTR,DALLAS,TX. UNIV CONNECTICUT,HARTFORD HOSP,MED CTR,HARTFORD,CT. LINKOPING UNIV HOSP,LINKOPING,SWEDEN. BAYLOR COLL MED,HOUSTON,TX. UNIV LUND HOSP,LUND,SWEDEN. VET AFFAIRS MED CTR,WASHINGTON,DC. HOP COCHIN,PARIS,FRANCE. UNIV MARYLAND HOSP,BALTIMORE,MD. ST GEORGE HOSP,LONDON,ENGLAND. MALMO GEN HOSP,MALMO,SWEDEN. UNIV WALES HOSP,CARDIFF,WALES. EALING GEN HOSP,SOUTHALL,MIDDX,ENGLAND. APACHE MED SYST INC,WASHINGTON,DC. RP FISHER, CJ (reprint author), CLEVELAND CLIN FDN,DEPT PULM & CRIT CARE MED,CRIT CARE RES UNIT,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. RI Porter, Joanna/C-7162-2009; Friedman, Gilberto/F-7212-2015; Friedman, Gilberto/F-7208-2015 OI Porter, Joanna/0000-0002-7307-169X; NR 37 TC 695 Z9 708 U1 1 U2 17 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 JUN 15 PY 1994 VL 271 IS 23 BP 1836 EP 1843 DI 10.1001/jama.271.23.1836 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA NP959 UT WOS:A1994NP95900027 PM 8196140 ER PT J AU LIPSITZ, SR KIM, K ZHAO, LP AF LIPSITZ, SR KIM, K ZHAO, LP TI ANALYSIS OF REPEATED CATEGORICAL-DATA USING GENERALIZED ESTIMATING EQUATIONS SO STATISTICS IN MEDICINE LA English DT Article ID CORRELATED BINARY REGRESSION; LINEAR-MODELS AB Moment methods for analysing repeated binary responses have been proposed by Liang and Zeger, and extended by Prentice and Zhao and Prentice. In these estimating equations, models are proposed for the correlation between the repeated binary responses. We extend Liang and Zeger's method to models for the correlation between repeated nominal or ordinal categorical responses; in particular, when the repeated responses are binary, our methods reduce to Liang and Zeger's method. Our method is illustrated with two datasets. One dataset contains repeated observations of self-assessment of arthritis, an ordered variable with three categories, collected during a randomized comparative study of alternative treatments of patients with rheumatoid arthritis. The second dataset is a longitudinal study of the health effects of air pollution, in which the repeated ordered multinomial response is the wheezing status (no wheeze, wheeze with cold, wheeze apart from cold) of a child at ages 9, 10, 11 and 12 years. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. FRED HUTCHINSON CANC RES CTR,PROGRAM EPIDEMIOL,SEATTLE,WA 98104. RP LIPSITZ, SR (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT BIOSTAT,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 55576]; NEI NIH HHS [EY 09252]; NIGMS NIH HHS [GM 29745] NR 21 TC 249 Z9 252 U1 2 U2 23 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 1994 VL 13 IS 11 BP 1149 EP 1163 DI 10.1002/sim.4780131106 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA NT802 UT WOS:A1994NT80200005 PM 8091041 ER PT J AU EASON, JD FREEMAN, RB ROHRER, RJ LEWIS, WD JENKINS, R DIENSTAG, J COSIMI, AB AF EASON, JD FREEMAN, RB ROHRER, RJ LEWIS, WD JENKINS, R DIENSTAG, J COSIMI, AB TI SHOULD LIVER-TRANSPLANTATION BE PERFORMED FOR PATIENTS WITH HEPATITIS-B SO TRANSPLANTATION LA English DT Article ID FIBROSING CHOLESTATIC HEPATITIS; HBSAG-POSITIVE PATIENTS; VIRUS-INFECTION; DISEASE; RECURRENCE; ALLOGRAFT; FAILURE; DNA AB Because of the almost universal recurrence of hepatitis B surface antigenemia (HBsAg) after liver trans plantation, some centers have questioned whether these patients are appropriate allograft candidates. Since January 1984, 51 patients with hepatitis B (HBV) underwent OLT at our center. No therapy was given to prevent reinfection. Three patients underwent retransplantation. The indications for transplant included fulminant HBV (13 patients), chronic HBV (33 patients), and hepatocellular carcinoma (HCCA) in addition to HBV (5 patients). Incidental HCCA was found in 2 of the 33 patients thought to have only chronic HBV. Actuarial survival for the entire group was 57% at 1 year and 54% at 3 years. Of the 23 patients who died, only 4 deaths were attributable to recurrent HBV liver disease. Four patients survived less than 4 days due to primary graft nonfunction. Ten patients died in the first 3 months from sepsis. Although all patients who died beyond 30 days had recurrent HBsAg, only 4 deaths were attributable to recurrent HBV. The remaining 5 deaths were caused by portal vein thrombosis, bile leak, lymphoma, pancreatitis, and sepsis occurring at 15 months. Excluding the 4 patients who died from primary graft nonfunction, actuarial survival was 63% at 1 year and 60% at 3 years. Of the 28 survivors, 24 are HBsAg positive; however, only 5 have recurrent HBV liver disease. Multiple factors were evaluated to determine their influence on survival; i.e., HBV serology, United Network for Organ Sharing status, fulminant versus chronic HBV, incidence of rejection, immunosuppression, transfusion requirements, and presence of HCCA. Of these, only the presence of HCCA adversely affected outcome. Of the 7 patients with HCCA and HBV, 6 patients died within the first 6 months and 1 patient has recurrent HBV liver disease at 25 months. Actuarial survival excluding those patients with HCCA was 64% at 1 year and 61% at 3 years. Based on our results, patients with HBV and associated HCCA have a poorer prognosis and should probably be excluded from transplantation. Although the survival for patients with HBV undergoing liver transplantation is inferior to that expected in patients with some other diagnoses, long-term survival can be achieved in a majority of these patients despite recurrence of HBsAg. We believe that appropriately selected patients with a diagnosis of HBV alone should continue to be candidates for liver allografts. C1 MASSACHUSETTS GEN HOSP,DEPT TRANSPLANT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT HEPATOL,BOSTON,MA 02114. NR 23 TC 23 Z9 23 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 JUN 15 PY 1994 VL 57 IS 11 BP 1588 EP 1593 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA NT393 UT WOS:A1994NT39300009 PM 8009592 ER PT J AU TROUTON, TG ONUNAIN, SS KIM, YH SOSASUAREZ, GE GARAN, H RUSKIN, JN AF TROUTON, TG ONUNAIN, SS KIM, YH SOSASUAREZ, GE GARAN, H RUSKIN, JN TI CURATIVE TRANSCATHETER RADIOFREQUENCY CURRENT ABLATION FOR ATRIOVENTRICULAR NODAL REENTRY TACHYCARDIA SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PARKINSON-WHITE SYNDROME; CATHETER ABLATION; SLOW-PATHWAY; CURE; CONDUCTION; ENERGY AB Background: To evaluate the efficacy of atrioventricular nodal modification by transcatheter ablation using radiofrequency energy in preventing electrically inducible and spontaneous symptomatic atrioventricular nodal reentry tachycardia, a prospective, nonrandomized, ''before-after'' trial was performed. Fifty consecutive patients with recurrent spontaneous symptomatic atrioventricular nodal reentry tachycardia referred to the Massachusetts General Hospital, Boston, were recruited. Methods: A diagnostic intracardiac electrophysiologic study was performed to define the mechanism of each patient's supraventricular tachycardia. Thereafter, selective ablation of one or more slow atrioventricular nodal pathways was attempted in 47 patients, and in three patients selective ablation of a retrograde fast atrioventricular nodal pathway was carried out. Repeated programmed cardiac stimulation was performed 30 minutes after catheter ablation therapy and, where possible, before hospital discharge to evaluate the presence of electrically inducible supraventricular tachycardia. Results: Electrically inducible atrioventricular nodal reentry tachycardia was eliminated in all 50 patients. No patient developed early heart block. During a mean (+/-SD) follow-up period of 8.9+/-5.3 months, three patients experienced a recurrence of spontaneous atrioventricular nodal reentry tachycardia and underwent a successful second ablation procedure. Two patients required permanent pacemaker implantation, one for symptomatic first-degree atrioventricular block and one for late complete heart block. Conclusions: Catheter ablation of slow atrioventricular nodal pathways by means of radiofrequency current is a safe and effective technique for eliminating electrically inducible and spontaneous atrioventricular nodal reentry tachycardia. C1 MASSACHUSETTS GEN HOSP,CARDIAC ARRHYTHMIA SERV,BOSTON,MA 02114. NR 20 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 13 PY 1994 VL 154 IS 11 BP 1226 EP 1231 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NQ330 UT WOS:A1994NQ33000005 PM 8203990 ER PT J AU HOROWITZ, MJ BLOCH, KD KIM, NB AMICO, JA AF HOROWITZ, MJ BLOCH, KD KIM, NB AMICO, JA TI EXPRESSION OF THE ENDOTHELIN-1 AND OXYTOCIN GENES IN THE HYPOTHALAMUS OF THE PREGNANT RAT SO BRAIN RESEARCH LA English DT Article DE ENDOTHELIN; GESTATION; HYPOTHALAMUS; NEUROHYPOPHYSIS; OXYTOCIN; PREGNANCY ID MESSENGER-RNA; SEQUENCE-ANALYSIS; OSMOTIC STIMULATION; TISSUE DISTRIBUTION; CDNA CLONING; VASOPRESSIN; HYBRIDIZATION; DYNORPHIN; RESPONSES; LACTATION AB Endothelin (ET)-1, a neuropeptide and possible neuromodulator, has been found in the hypothalamic supraoptic and paraventricular nuclei (SON and PVN) of the rat in the distribution of oxytocin (OT) neurons. Within the hypothalamus of the pregnant rat, we investigated the developmental expression of the ET-1 gene and the possibility of coordinate expression of the ET-1 and OT genes. Blots containing hypothalamic mRNAs from 4-, 14-, 18-, and 21-day-old pregnant rats were hybridized to a P-32-labeled probe specific to the rat ET-1 gene. Hypothalamic tissue contained an ET-1 transcript of approximate to 2.3 kb size. ET-1 mRNA abundance increased significantly in the SON and PVN from early to late gestation (P = 0.005 and 0.05, respectively). Blots containing hypothalamic mRNA were rehybridized to a P-32-labeled probe specific to exon C of the rat OT gene. OT gene expression increased significantly within both the hypothalamic SON (P = 0.0009) and PVN (P = 0.003) as gestation advanced. The sizes of the hypothalamic ET-1 and OT transcript sizes remained unchanged throughout gestation. Hypothalamic ET-1 and OT transcripts display stage-specific increases during gestation. ET-1 may be a neuroendocrine regulator of pregnancy-related events in the rat, and may act alone or in concert with OT. C1 UNIV PITTSBURGH,SCH MED,DEPT MED,DIV ENDOCRINOL & METAB,PITTSBURGH,PA 15261. MASSACHUSETTS GEN HOSP,MED SERV,CARDIAC UNIT,BOSTON,MA 02114. NR 28 TC 5 Z9 5 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 JUN 13 PY 1994 VL 648 IS 1 BP 59 EP 64 PG 6 WC Neurosciences SC Neurosciences & Neurology GA NQ543 UT WOS:A1994NQ54300009 ER PT J AU MCCAFFREY, PG KIM, PK VALGEARCHER, VE SEN, R RAO, A AF MCCAFFREY, PG KIM, PK VALGEARCHER, VE SEN, R RAO, A TI CYCLOSPORINE-A SENSITIVITY OF THE NF-KAPPA-B SITE OF THE IL2R-ALPHA PROMOTER IN UNTRANSFORMED MURINE T-CELLS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RECEPTOR-ALPHA-GENE; DNA-BINDING PROTEINS; LYMPHOCYTE-SPECIFIC FACTORS; LONG TERMINAL REPEAT; INTERLEUKIN-2 GENE; CHAIN GENE; TRANSCRIPTION FACTORS; REGULATORY ELEMENTS; ENHANCER ELEMENTS; ANTIGEN RECEPTOR AB We have investigated the characteristics of IL2R alpha gene induction in untransformed murine T cells. Induction of IL2R alpha mRNA by TCR/CD3 ligands in a murine T cell clone and in short-term splenic T cell cultures was inhibited by protein synthesis inhibitors and by CsA. This result was contrary to previous observations in JURKAT T leukemia cells and human peripheral blood T cells, suggesting a difference in the mechanisms of IL2R alpha gene induction in these different cell types. The CsA sensitivity of IL2R alpha mRNA induction represented a direct effect on the TCR/CD3 response, and was not due to CsA-sensitive release of the lymphokines IL2 or tumour necrosis factor alpha (TNF alpha) and consequent lymphokine-mediated induction of IL2R alpha mRNA. The NF-kappa B site of the IL2R alpha promoter was essential for gene induction through the TCR/CD3 complex, and the induction of reporter plasmids containing multimers of this site was significantly inhibited by CsA. Northern blotting analysis indicated that while the p65 subunit of NF-kappa B was constitutively expressed and not appreciably induced upon T cell activation, mRNA for the p105 precursor of p50 NF-kappa B was induced in response to TCR/CD3 stimulation and this induction was sensitive to CsA. Electrophoretic mobility shift assays and antiserum against the p50 subunit of NF-kappa B indicated that p50 was a component of the inducible nuclear complex that bound to the IL2R alpha kappa B site. Appearance of the kB-binding proteins was insensitive to CsA at early times after activation (similar to 15 min), but was partially sensitive to CsA at later times. Based on these results, we propose that the NF-kappa B site of the IL2R alpha promoter mediates at least part of the CsA sensitivity of IL2R alpha gene induction in untransformed T cells, possibly because de novo synthesis of p105 NF-kappa B is required for sustained IL2R alpha expression. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,WALTHAM,MA 02254. BRANDEIS UNIV,DEPT BIOL,WALTHAM,MA 02254. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. FU NCI NIH HHS [CA42471] NR 58 TC 42 Z9 42 U1 0 U2 0 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 JUN 11 PY 1994 VL 22 IS 11 BP 2134 EP 2142 DI 10.1093/nar/22.11.2134 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NT818 UT WOS:A1994NT81800029 PM 8029023 ER PT J AU KAJIWARA, K BERSON, EL DRYJA, TP AF KAJIWARA, K BERSON, EL DRYJA, TP TI DIGENIC RETINITIS-PIGMENTOSA DUE TO MUTATIONS AT THE UNLINKED PERIPHERIN/RDS AND ROM1 LOCI SO SCIENCE LA English DT Article ID SYNDROME TYPE-I; SLOW RDS GENE; NULL MUTATION; LOCALIZATION; LINKAGE; DEGENERATION; FAMILY; CHROMOSOME-11; DYSTROPHY; HETEROGENEITY AB In spite of recent advances in identifying genes causing monogenic human disease, very little is known about the genes involved in polygenic disease. Three families were identified with mutations in the unlinked photoreceptor-specific genes ROM1 and peripherin/RDS, in which only double heterozygotes develop retinitis pigmentosa (RP). These findings indicate that the allelic and nonallelic heterogeneity known to be a feature of monogenic RP is complicated further by interactions between unlinked mutations causing digenic RP. Recognition of the inheritance pattern exemplified by these three families might facilitate the identification of other examples of digenic inheritance in human disease. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HOWE LAB OPHTHALMOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114. FU NEI NIH HHS [EY00169, EY08683] NR 40 TC 452 Z9 464 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 10 PY 1994 VL 264 IS 5165 BP 1604 EP 1608 DI 10.1126/science.8202715 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NQ285 UT WOS:A1994NQ28500041 PM 8202715 ER PT J AU PLATT, OS BRAMBILLA, DJ ROSSE, WF MILNER, PF CASTRO, O STEINBERG, MH KLUG, PP AF PLATT, OS BRAMBILLA, DJ ROSSE, WF MILNER, PF CASTRO, O STEINBERG, MH KLUG, PP TI MORTALITY IN SICKLE-CELL DISEASE - LIFE EXPECTANCY AND RISK-FACTORS FOR EARLY DEATH SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALPHA-GLOBIN GENE; FAT-EMBOLISM; PAIN CRISIS; CHILDREN; THALASSEMIA; ANEMIA AB Background. Information on life expectancy and risk factors for early death among patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, and the sickle cell-P-thalassemias) is needed to counsel patients, target therapy, and design clinical trials. Methods. We followed 3764 patients who ranged from birth to 66 years of age at enrollment to determine the life expectancy and calculate the median age at death. In addition, we investigated the circumstances of death for all 209 adult patients who died during the study, and used proportional-hazards regression analysis to identify risk factors for early death among 964 adults with sickle cell anemia who were followed for at least two years. Results. Among children and adults with sickle cell anemia (homozygous for sickle hemoglobin), the median age at death was 42 years for males and 48 years for females. Among those with sickle cell-hemoglobin C disease, the median age at death was 60 years for males and 68 years for females. Among adults with sickle cell disease, 18 percent of the deaths occurred in patients with overt organ failure, predominantly renal. Thirty-three percent were clinically free of organ failure but died during an acute sickle crisis (78 percent had pain, the chest syndrome, or both; 22 percent had stroke). Modeling revealed that in patients with sickle cell anemia, the acute chest syndrome, renal failure, seizures, a base-line white-cell count above 15,000 cells per cubic millimeter, and a low level of fetal hemoglobin were associated with an increased risk of early death. Conclusions. Fifty percent of patients with sickle cell anemia survived beyond the fifth decade. A large proportion of those who died had no overt chronic organ failure but died during an acute episode of pain, chest syndrome, or stroke. Early mortality was highest among patients whose disease was symptomatic. A high level of fetal hemoglobin predicted improved survival and is probably a reliable childhood forecaster of adult life expectancy. C1 CHILDRENS HOSP,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. NEW ENGLAND RES INST,WATERTOWN,MA. DUKE UNIV,SCH MED,DEPT MED,DURHAM,NC 27706. MED COLL GEORGIA,DEPT MED,AUGUSTA,GA 30912. HOWARD UNIV,CTR SICKLE CELL DIS,DEPT MED,WASHINGTON,DC. DEPT VET AFFAIRS MED CTR,HEMATOL ONCOL SECT,JACKSON,MS. UNIV MISSISSIPPI,SCH MED,DEPT MED,JACKSON,MS. TEXAS TECH UNIV,HLTH SCI CTR,DIV HEMATOL,AMARILLO,TX. NR 21 TC 1460 Z9 1496 U1 20 U2 102 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 JUN 9 PY 1994 VL 330 IS 23 BP 1639 EP 1644 DI 10.1056/NEJM199406093302303 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NP220 UT WOS:A1994NP22000003 PM 7993409 ER PT J AU RATTNER, DW PINS, MR BOLAND, GWI DELMONICO, FL WARSHAW, AL AF RATTNER, DW PINS, MR BOLAND, GWI DELMONICO, FL WARSHAW, AL TI A 37-YEAR-OLD MAN WITH SEVERAL BOUTS OF ACUTE-PANCREATITIS AND PANCREATIC-DUCT FILLING DEFECTS - MUCINOUS VILLOUS ADENOMATOSIS, ATYPICAL, INVOLVING DILATED SEGMENT OF MAIN PANCREATIC DUCT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Discussion ID OBSTRUCTIVE PANCREATITIS; CYSTIC TUMORS; CYSTADENOMA; DIAGNOSIS; NEOPLASMS; CARCINOMA; ECTASIA C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP RATTNER, DW (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA, USA. NR 27 TC 4 Z9 4 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 9 PY 1994 VL 330 IS 23 BP 1671 EP 1676 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NP220 UT WOS:A1994NP22000008 ER PT J AU NASH, IS AF NASH, IS TI CASE-2-1994 - TRICUSPID REGURGITATION - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP NASH, IS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 9 PY 1994 VL 330 IS 23 BP 1688 EP 1689 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NP220 UT WOS:A1994NP22000027 ER PT J AU HENGST, L DULIC, V SLINGERLAND, JM LEES, E REED, SI AF HENGST, L DULIC, V SLINGERLAND, JM LEES, E REED, SI TI A CELL-CYCLE-REGULATED INHIBITOR OF CYCLIN-DEPENDENT KINASES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE; CDK2 ACTIVITY; PHASE; G1; G(1)-CYCLINS; TUMOR; P21 AB Cyclin-dependent kinases (Cdks) previously have been shown to drive the major cell cycle transitions in eukaryotic organisms ranging from yeast to humans. We report here the identification of a 28-kDa protein, p28(Ick) (inhibitor of cyclin-dependent kinase), that binds to and inhibits the kinase activity of preformed Cdk/cyclin complexes from human cells. p28 inhibitory activity fluctuates during the cell cycle with maximal levels in G(1) and accumulates in G(1)- and G(0)-arrested cells. These results suggest that control of the G(1)/S transition may be influenced by a family of Cdk inhibitors that include p28(Ick) and the recently described inhibitors p21(Cip1/Waf1/Cap20) and p16(Ink4). C1 MASSACHUSETTS GEN HOSP, CTR CANC, MOLEC ONCOL LAB, BOSTON, MA 02129 USA. RP HENGST, L (reprint author), SCRIPPS RES INST, DEPT MOLEC BIOL, MB-7, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. OI Dulic, Vjekoslav/0000-0003-1201-3901 FU NIGMS NIH HHS [GM4006] NR 23 TC 254 Z9 255 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5291 EP 5295 DI 10.1073/pnas.91.12.5291 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500016 PM 8202483 ER PT J AU KHARBANDA, S SALEEM, A SHAFMAN, T EMOTO, Y WEICHSELBAUM, R KUFE, D AF KHARBANDA, S SALEEM, A SHAFMAN, T EMOTO, Y WEICHSELBAUM, R KUFE, D TI ACTIVATION OF THE PP90(RSK) AND MITOGEN-ACTIVATED SERINE/THREONINE PROTEIN-KINASES BY IONIZING-RADIATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LYMPHOCYTE-B PRECURSORS; SERUM RESPONSE FACTOR; C-FOS PROMOTER; MONOCYTIC DIFFERENTIATION; SIGNAL-TRANSDUCTION; BINDING-ACTIVITY; MAP KINASE; S6 KINASE; PHOSPHORYLATION; IDENTIFICATION AB The cellular response to ionizing radiation (IR) includes induction of the c-jun and EGR1 early response genes. The present work has examined potential cytoplasmic signaling cascades that transduce IR-induced signals to the nucleus. The results demonstrate activation of the 40S ribosomal protein S6 kinase, pp9O(rsk), in human U-937 myeloid leukemia cells. Partial purification of pp90(rsk) by affinity chromatography demonstrated an increase in S6 peptide phosphorylation when comparing irradiated with control cells. IR-induced activation of pp90(rsk) was further confirmed in immune-complex kinase assays. In contrast to these findings, there was no detectable induction of pp70(S6K). Previous work has demonstrated that mitogen-activated protein kinase activates pp9O(rsk). The present results further show that IR treatment is associated with induction of mitogen-activated protein kinase activity and that this event is temporally related to activation of pp90(rsk) and early response gene expression. These findings suggest that activation of the mitogen-activated protein kinase/pp90(rsk) cascade is involved in the response of cells to IR exposure. C1 UNIV CHICAGO,PRITZKER SCH MED,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. RP KHARBANDA, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA55241] NR 42 TC 54 Z9 55 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5416 EP 5420 DI 10.1073/pnas.91.12.5416 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500042 PM 8202500 ER PT J AU VIDARD, L COLARUSSO, LJ BENACERRAF, B AF VIDARD, L COLARUSSO, LJ BENACERRAF, B TI SPECIFIC T-CELL TOLERANCE MAY BE PRECEDED BY A PRIMARY RESPONSE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE REFRACTORINESS; ANERGY; APOPTOSIS ID CTLA-4 COUNTER-RECEPTOR; MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; ORAL TOLERANCE; IMMUNOLOGICAL-TOLERANCE; CLONAL ELIMINATION; SELF-TOLERANCE; LYMPHOCYTES-T; ANTIGEN; MICE AB We have evaluated the ability of ovalbumin to induce T-cell-specific tolerance in SJL mice. A significant decrease of interleukin 2 in lymph-node culture supernatants from tolerant mice upon antigen stimulation was seen. Oral tolerization was less effective than i.p.- or s.c.-tolerization protocols. Transfer experiments of either splenic or lymphnode T cells from tolerant mice to naive mice definitely ruled out suppression as a mechanism involved in tolerant mite. Surprisingly, we found that, before the establishment of specific T-cell tolerance to ovalbumin, T cells from mice that will display tolerance were responsive and synthesized interleukin 2 upon antigen challenge in vitro. Thus, we concluded that anergy cannot account solely for the T-cell unresponsiveness in tolerant mice. Furthermore, although we cannot rule out the hypothesis that the T-cell unresponsiveness in tolerant mice can be explained by programmed cell death of ovalbumin-specific T cells, these data led us to speculate that T-cell ''refractoriness'' could explain the drop of interleukin 2 production in lymph-node T-cell culture supernatant from tolerant mice. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP VIDARD, L (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-46967] NR 36 TC 44 Z9 46 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 1994 VL 91 IS 12 BP 5627 EP 5631 DI 10.1073/pnas.91.12.5627 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NR275 UT WOS:A1994NR27500085 PM 8202538 ER PT J AU WULLNER, U STANDAERT, DG TESTA, CM LANDWEHRMEYER, GB CATANIA, MV PENNEY, JB YOUNG, AB AF WULLNER, U STANDAERT, DG TESTA, CM LANDWEHRMEYER, GB CATANIA, MV PENNEY, JB YOUNG, AB TI GLUTAMATE-RECEPTOR EXPRESSION IN RAT STRIATUM - EFFECT OF DEAFFERENTATION SO BRAIN RESEARCH LA English DT Article DE N-METHYL-D-ASPARTATE; AMPA; KAINATE; METABOTROPIC; DECORTICATION; NEOSTRIATUM ID ACID BINDING; DIFFERENTIAL EXPRESSION; MESSENGER-RNAS; MOLECULAR CHARACTERIZATION; CEREBRAL-CORTEX; GENE-EXPRESSION; BASAL GANGLIA; NMDA RECEPTOR; BRAIN; LESIONS AB The cerebral cortex is the primary source of glutamatergic afferents to the neostriatum. We used in situ hybridization to examine the effect of removal of the glutamatergic input to the striatum by unilateral frontal cortical ablation on the expression of genes encoding subunits from three families of glutamate receptors: N-methyl-D-aspartate receptors (NMDAR1, NMDAR2A, and NMDAR2B); alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (GluR1-4, flip and flop splice variants); and metabotropic receptors (mGluR1-5). Significant changes were restricted to the dorsolateral quadrant of the ipsilateral striatum, the main projection area of the sensorimotor cortex. The expression of those messages which are normally abundant, NMDAR1, NMDAR2A, GluR1-4 flop and mGluR1, 3 and 5, was decreased in the deafferented dorsolateral striatum by 10-39% at 3 days after cortical ablation and subsequently increased to 120-165% of control at 15 and 60 days. mRNAs encoding the flip isoforms of GluR1-4, mGluR2 and 4, and an alternatively spliced region of NMDAR1 (Insertion I) which are undetectable or present at low levels in the striatum were not induced by cortical ablation. In contrast, both glial fibrillary acid protein and p-actin mRNA expression were; markedly enhanced at 3 and 15 days, returning to near normal at 60 days. Striatal NMDA, AMPA and metabotropic type 1 ligand binding sites were increased as early as 3 days after cortical ablation, reached a peak at 15 days and remained increased for up to 60 days, while metabotropic type 2 binding was slightly but significantly reduced at 3 and 15 days and [H-3]kainate binding did not change significantly. These results demonstrate that cortical ablation, and subsequent loss of glutamatergic afferents to the striatum, results in alterations in the expression of genes encoding glutamate receptor subunits in striatal neurons. The regulation of these genes appears to be coordinate, so that the relative abundance of the different messages is preserved. C1 MASSACHUSETTS GEN HOSP, NEUROL SERV, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RI Catania, Maria Vincenza/E-2627-2017; OI Catania, Maria Vincenza/0000-0002-9329-8517; Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS19613] NR 45 TC 63 Z9 63 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JUN 6 PY 1994 VL 647 IS 2 BP 209 EP 219 DI 10.1016/0006-8993(94)91320-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA NT439 UT WOS:A1994NT43900005 PM 7922497 ER PT J AU COGNE, M LANSFORD, TR BOTTARO, A ZHANG, J GORMAN, J YOUNG, F CHENG, HL ALT, FW AF COGNE, M LANSFORD, TR BOTTARO, A ZHANG, J GORMAN, J YOUNG, F CHENG, HL ALT, FW TI CLASS SWITCH CONTROL REGION AT THE 3' END OF THE IMMUNOGLOBULIN HEAVY-CHAIN LOCUS SO CELL LA English DT Article ID BETA-GLOBIN LOCUS; MURINE-B-CELLS; GROWTH FACTOR-BETA; CONSTANT-REGION; C-EPSILON; INTERFERON-GAMMA; IGH ENHANCER; GENE; EXPRESSION; TRANSCRIPTS AB We replaced the IgH 3' enhancer (3'E(H)) region with a neomycin resistance gene in ES cells and generated chimeric mice in which all mature lymphocytes were either heterozygous (3'E(H)(+/-)) or homozygous (3'E(H)(-/-)) for the mutation. In vitro activated 3'E(H)(-/-) B cells responded similarly to 3'E(H)(+/-) B cells with respect to proliferation and secretion of IgM and IgG1 but were specifically deficient in IgG2a, IgG2b, IgG3, and IgE secretion. These isotype deficiencies correlated with a deficiency in accumulation of transcripts from and class switching to affected C-H genes. In vivo, chimeric mice containing only 3'E(H)(-/-) B cells were deficient in serum IgG2a and IgG3. We propose that the 3'E(H)(-/-) mutation disrupts the activity of a regulatory region that influences heavy chain class switching to several different C-H genes that lie as far as 100 kb upstream of the mutation. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. FAC SCI POITIERS,INST BIOL MOLEC & INGN GENET,CNRS,URA 1172,F-86022 POITIERS,FRANCE. UNIV SIENA,POLICLIN SCOTTE,DIPARTIMENTO BIOL MOLEC,I-53100 SIENA,ITALY. RP COGNE, M (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,HOWARD HUGHES MED INST,CTR BLOOD RES,BOSTON,MA 02115, USA. RI cogne, michel/D-7370-2015 OI cogne, michel/0000-0002-8519-4427 FU NIAID NIH HHS [AI-20047, AI-31541] NR 76 TC 208 Z9 209 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUN 3 PY 1994 VL 77 IS 5 BP 737 EP 747 DI 10.1016/0092-8674(94)90057-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NQ123 UT WOS:A1994NQ12300013 PM 8205622 ER PT J AU CROSSLEY, M TSANG, AP BIEKER, JJ ORKIN, SH AF CROSSLEY, M TSANG, AP BIEKER, JJ ORKIN, SH TI REGULATION OF THE ERYTHROID KRUPPEL-LIKE FACTOR (EKLF) GENE PROMOTER BY THE ERYTHROID TRANSCRIPTION FACTOR GATA-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOX-BINDING-PROTEINS; DNA-BINDING; GLOBIN GENE; POSITIVE REGULATOR; MAMMALIAN-CELLS; CACCC ELEMENT; EXPRESSION; FAMILY; MOUSE; DIFFERENTIATION AB Erythroid Kruppel-like factor (EKLF) is an erythroid-specific transcription factor that binds a CACCC motif found in the human beta-globin gene promoter. We have studied the promoter of the EKLF gene and identified binding sites for the transcription factors GATA-1 and CCAAT-binding Protein 1 (CP1). We show that both types of binding sites are required for full activity, and that the GATA motif at -60 is essential. The EKLF promoter can be directly activated in nonerythroid cells in col transfection experiments by forced expression of GATA-1. These results suggest that EKLF is dependent on GATA-1 for its expression and lies downsteam of, or coincident with, GATA-1 in a regulatory hierarchy in erythroid development. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV HEMATOL ONCOL,BOSTON,MA 02115. HOWARD HUGHES MED INST,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,BROOKDALE CTR MOLEC BIOL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT BIOCHEM,NEW YORK,NY 10029. RI Crossley, Merlin/D-7888-2011 OI Crossley, Merlin/0000-0003-2057-3642 NR 30 TC 87 Z9 88 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 JUN 3 PY 1994 VL 269 IS 22 BP 15440 EP 15444 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300010 PM 8195185 ER PT J AU ZHANG, YJ RUTLEDGE, BJ ROLLINS, BJ AF ZHANG, YJ RUTLEDGE, BJ ROLLINS, BJ TI STRUCTURE/ACTIVITY ANALYSIS OF HUMAN MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) BY MUTAGENESIS - IDENTIFICATION OF A MUTATED PROTEIN THAT INHIBITS MCP-1-MEDIATED MONOCYTE CHEMOTAXIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 3-DIMENSIONAL STRUCTURE; RECOMBINANT PROTEINS; RECEPTOR-BINDING; CYTOKINE FAMILY; JE GENE; INTERLEUKIN-8; CELLS; PURIFICATION; RESIDUES AB Monocyte chemoattractant protein-1 (MCP-1) is a monocyte-specific chemoattractant and activator and is a member of the chemokine-beta family of cytokines. To identify regions of MCP-1 which are required for its biological activity, me constructed human MCP-1 mutants that were expressed in eukaryotic cells and tested for their ability to attract monocytes in vitro. Deletion of amino acids 2-8 destroyed activity, suggesting that the amino-terminal region is necessary for activity. Within the deleted region, mutation of aspartate 3 to alanine produced a protein with 9% of wild-type activity, whereas mutation of asparagine 6 to alanine produced a protein with 52.9% of wild-type activity. Mutation of amino acids within the first intercysteine loop yielded variable results. Changing tyrosine 28 to aspartate or arginine 30 to leucine each produced proteins with essentially no monocyte chemoattractant activity. The side chains of these amino acids are predicted to point into a putative receptor binding cleft, and these loss-of-function mutations are consistent with this model. Also consistent is the retention of 60% of wad-type activity after mutation of serine 27 to glutamine, since the side chain of serine 27 is predicted to point away from the binding cleft. However, mutation of arginine 24, which lies outside of this area, to phenylalanine produced a protein with only 5% of wild-type activity, suggesting more complex interactions. Truncations of the carboxyl terminus, as well as mutation of aspartate 68 to leucine, generated proteins with 10-20% of wild-type activity. (Another carboxyl-terminal insertional mutation demonstrated that O-linked carbohydrate in MCP-l alpha may be added to a threonine in the carboxyl-terminal region.) These findings are consistent with a structural model of dimeric MCP-1 which is similar to interleukin-8 in which amino acids that point into a cleft between the two carboxyl-terminal alpha-helices of the subunits are important for receptor binding. In addition, however, amino acids at the amino terminus and others outside of the interhelical cleft are also essential for activity. The carboxyl terminal alpha-helix is not required for signaling per se but is required for maximal specific activity. Finally, four mutant proteins partially inhibited the ability of wild-type MCP-1 to attract monocytes in vitro. In particular, mutant 7ND (deletion of amino acids 2-8) in hibited MCP-1 activity by 50% at a molar ratio of 75:1, displaced MCP-1 from its receptor on monocytes at a similar ratio, and bound to a single class of receptors on human monocytes with a K-d of 2.6 nM. However, 7ND bound only to 10% of the number of receptors to which MCP-1 bound, suggesting that part of its inhibitory activity may be due to binding to MCP-1 itself. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. FU NCI NIH HHS [CA53091] NR 30 TC 139 Z9 140 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 JUN 3 PY 1994 VL 269 IS 22 BP 15918 EP 15924 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP513 UT WOS:A1994NP51300080 PM 8195247 ER PT J AU HALACHMI, S MARDEN, E MARTIN, G MACKAY, H ABBONDANZA, C BROWN, M AF HALACHMI, S MARDEN, E MARTIN, G MACKAY, H ABBONDANZA, C BROWN, M TI ESTROGEN RECEPTOR-ASSOCIATED PROTEINS - POSSIBLE MEDIATORS OF HORMONE-INDUCED TRANSCRIPTION SO SCIENCE LA English DT Article ID HUMAN GLUCOCORTICOID RECEPTOR; DNA-BINDING; TRANSACTIVATION DOMAINS; FUNCTIONAL DOMAINS; GENE ACTIVATION; IDENTIFICATION; EXPRESSION; MULTIPLE; INHIBITION; REGION AB The estrogen receptor is a transcription factor which, when bound to estradiol, binds DNA and regulates expression of estrogen-responsive genes. A 160-kilodalton estrogen receptor-associated protein, ERAP160, was identified that exhibits estradiol-dependent binding to the receptor. Mutational analysis of the receptor shows that its ability to activate transcription parallels its ability to bind ERAP160. Antiestrogens are unable to promote ERAP160 binding and can block the estrogen-dependent interaction of the receptor and ERAP160 in a dose-dependent manner. This evidence suggests that ERAP160 may mediate estradiol-dependent transcriptional activation by the estrogen receptor. Furthermore, the ability of antiestrogens to block estrogen receptor-ERAP160 complex formation could account for their therapeutic effects in breast cancer. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM BIOL & BIOMED SCI,BOSTON,MA 02115. FAC MED & CHIRURG NAPLES,INST PATOL GEN & ONCOL,I-80138 NAPLES,ITALY. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 NR 37 TC 552 Z9 558 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 3 PY 1994 VL 264 IS 5164 BP 1455 EP 1458 DI 10.1126/science.8197458 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NP221 UT WOS:A1994NP22100041 PM 8197458 ER PT J AU SCHNEIDER, JW GU, W ZHU, L MAHDAVI, V NADALGINARD, B AF SCHNEIDER, JW GU, W ZHU, L MAHDAVI, V NADALGINARD, B TI REVERSAL OF TERMINAL DIFFERENTIATION MEDIATED BY P107 IN RB(-/-) MUSCLE-CELLS SO SCIENCE LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; LARGE T-ANTIGEN; CYCLIN-A; MYOGENIC DIFFERENTIATION; SUSCEPTIBILITY GENE; PROTEIN; EXPRESSION; RHABDOMYOSARCOMAS; PROLIFERATION; SUPPRESSION AB The terminal differentiation of mammalian muscle cells requires the tumor suppressor retinoblastoma protein (Rb). Unlike their wild-type counterparts, multinucleated myotubes from mouse cells deficient in Rb (Rb--/-) were induced by serum to reenter the cell cycle. Development of the myogenic phenotype in Rb--/- cells correlated with increased expression of p107, which interacted with myogenic transcription factors. Serum-induced cell cycle reentry, on the other hand, correlated with decreased p107 expression. Thus, although p107 could substitute for Rb as a cofactor for differentiation, it could not maintain the terminally differentiated state in Rb--/- myotubes. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT CARDIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. NR 42 TC 340 Z9 343 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUN 3 PY 1994 VL 264 IS 5164 BP 1467 EP 1471 DI 10.1126/science.8197461 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NP221 UT WOS:A1994NP22100045 PM 8197461 ER PT J AU STOREY, E CIPOLLONI, PB FERRRANTE, RJ KOWALL, NW BEAL, MF AF STOREY, E CIPOLLONI, PB FERRRANTE, RJ KOWALL, NW BEAL, MF TI MOVEMENT DISORDER FOLLOWING EXCITOTOXIN LESIONS IN PRIMATES SO NEUROREPORT LA English DT Article DE EXCITOTOXICITY; HUNTINGTONS DISEASE; NMDA; QUINOLINIC ACID; PRIMATES; CHOREA; MOVEMENT DISORDER ID HUNTINGTONS-DISEASE; QUINOLINIC ACID; PARKINSONS-DISEASE; MODEL; DYSKINESIA; PUTAMEN; CHOREA AB WE previously reported on the histologic and neurochemical features of quinolinic acid lesions in primates which produce many of the characteristic features of Huntington's disease (HD). We now report on the effects of apomorphine in generating a movement disorder in four of these animals. Animals were tested with saline or apomorphine both before and after the lesions. All animals showed few spontaneous abnormal movements after lesioning, but showed marked dyskinetic movements following apomorphine administration. These results show that excitotoxin lesions in primates can produce an apomorphine-inducible movement disorder which closely resembles that of HD. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,NEUROCHEM LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,BEDFORD,MA. BOSTON UNIV,SCH MED,DEPT ANAT,BOSTON,MA 02115. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02115. RI Kowall, Neil/G-6364-2012; Storey, Elsdon/A-9889-2013 OI Kowall, Neil/0000-0002-6624-0213; FU DS NIH HHS [NINDS 16367]; NINDS NIH HHS [NS10828, NS31579] NR 17 TC 20 Z9 20 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 2 PY 1994 VL 5 IS 10 BP 1259 EP 1261 PG 3 WC Neurosciences SC Neurosciences & Neurology GA NU290 UT WOS:A1994NU29000023 PM 7919178 ER PT J AU AFRIDI, I QUINONES, MA ZOGHBI, WA CHEIRIF, J AF AFRIDI, I QUINONES, MA ZOGHBI, WA CHEIRIF, J TI DOBUTAMINE STRESS ECHOCARDIOGRAPHY - SENSITIVITY, SPECIFICITY, AND PREDICTIVE VALUE FOR FUTURE CARDIAC EVENTS SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; EXERCISE ECHOCARDIOGRAPHY; PROGNOSTIC VALUE AB We conducted a retrospective study to determine whether dobutamine stress echocardiography (DE) can be used for risk stratification of patients with known or suspected coronary artery disease (CAD). The study population consisted of 77 patients who underwent DE at our institution. The protocol consisted of an echocardiogram at baseline followed by imaging during intravenous dobutamine infusion starting at 10 mu g/kg/min with increments of 10 mu g/kg/min every 3 minutes to a maximum dose of 40 mu g/kg/min. The reasons for performing DE included preoperative cardiac evaluation (30), chest pain (23), assessment of ischemia (18), and suspected, restenosis (6). DE was classified according to wall motion response as normal (before and during DE), fixed abnormal (abnormal before with no change during DE), or ischemic (new wall-motion abnormality during DE). Mean duration of follow-up was 10 months. Cardiac events occurred in 14 patients. These included congestive heart failure in seven patients, myocardial infarction-in six, and cardiac death in one. A normal wall-motion response (n = 40) was associated with a low incidence of cardiac events (5%), whereas 5 of 10 patients (50%) with an ischemic response had events. The risk of cardiac events was intermediate (26%) in patients with fixed abnormal wall motion. Overall sensitivity of DE for predicting future cardiac events was 85%. In 45 patients who underwent coronary angiography within 2 months of DE, the test detected CAD with a sensitivity of 71%. In conclusion, the wall-motion response during DE may be used for identifying patients at high risk for future cardiac events. C1 BAYLOR COLL MED,VET ADM HOSP,DEPT INTERNAL MED,CARDIOL SECT,HOUSTON,TX. FU NCRR NIH HHS [RR-00350] NR 17 TC 76 Z9 77 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1994 VL 127 IS 6 BP 1510 EP 1515 DI 10.1016/0002-8703(94)90378-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NQ301 UT WOS:A1994NQ30100011 PM 8197976 ER PT J AU EAGLE, KA AF EAGLE, KA TI BEDSIDE PULMONARY-ARTERY CATHETERIZATION - REPLY SO AMERICAN HEART JOURNAL LA English DT Letter RP EAGLE, KA (reprint author), MASSACHUSETTS GEN HOSP,CTR AMBULATORY CARE,CARDIAC UNIT,SUITE 469,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 1994 VL 127 IS 6 BP 1666 EP 1666 DI 10.1016/0002-8703(94)90420-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NQ301 UT WOS:A1994NQ30100053 ER PT J AU SAYEGH, RA AF SAYEGH, RA TI PREMENSTRUAL-SYNDROME DOES EXIST SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter RP SAYEGH, RA (reprint author), MASSACHUSETTS GEN HOSP,VINCENT MEM GYNECOL SERV,BOSTON,MA 02114, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 1994 VL 59 IS 6 BP 1419 EP 1419 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NP044 UT WOS:A1994NP04400028 PM 8198071 ER PT J AU BONOMI, P FINKELSTEIN, D CHANG, A AF BONOMI, P FINKELSTEIN, D CHANG, A TI PHASE-II TRIAL OF ACIVICIN VERSUS ETOPOSIDE-CISPLATIN IN NONSMALL CELL LUNG-CANCER - AN EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE ACIVICIN; ETOPOSIDE; CISPLATIN; NONSMALL CELL LUNG CANCER ID CHEMOTHERAPY; REGIMENS AB Identification of effective new chemotherapeutic agents is a major objective of clinical research efforts in patients who have metastatic non-small cell lung cancer (NSCLC). Canadian investigators observed responses in NSCLC when acivicin was given as a daily IV bolus for 5 consecutive days. Based on these results the Eastern Cooperative Oncology Group tested acivicin as a continuous infusion in patients with advanced NSCLC. A total of 82 patients were entered on a Phase II trial in which patients have randomized either to acivicin 60 mg/m2 given as a continuous intravenous infusion over 72 hours repeated every 28 days or to the reference regimen which consisted of cisplatin 60 mg/m2 intravenously on day 1 and etoposide 120 mg/m2 daily on days 1, 2, and 3 repeated every 28 days. Five partial remissions (11%) were observed in 42 patients treated with etoposide-cisplatin, and no responses were observed in 40 patients treated with acivicin. Median survival durations for etoposide cisplatin and for acivicin were 29.7 and 21.1 weeks, respectively. Based on these results, acivicin appears to be inactive in NSCLC. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14627. FU NCI NIH HHS [CA 11083, CA 23318, CA 25988] NR 8 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD JUN PY 1994 VL 17 IS 3 BP 215 EP 217 DI 10.1097/00000421-199406000-00006 PG 3 WC Oncology SC Oncology GA NP055 UT WOS:A1994NP05500006 PM 8192104 ER PT J AU KORRICK, SA REST, KM DAVIS, LK CHRISTIANI, DC AF KORRICK, SA REST, KM DAVIS, LK CHRISTIANI, DC TI USE OF STATE WORKERS COMPENSATION DATA FOR OCCUPATIONAL CARPAL-TUNNEL SYNDROME SURVEILLANCE - A FEASIBILITY STUDY IN MASSACHUSETTS SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE REPETITION STRAIN INJURY; OCCUPATIONAL DISEASES; POPULATION SURVEILLANCE; INDUSTRY; OCCUPATION; WORKERS COMPENSATION DATA ID CUMULATIVE TRAUMA DISORDERS AB The purpose of this study was to determine the feasibility of using Massachusetts workers' compensation data for passive surveillance of occupational carpal tunnel syndrome (OCTS). Workers' compensation claims for OCTS (n = 358) and for possible cases of OCTS (n = 1,121) active during the first 6 months of 1989 were identified. The availability and distribution of demographic and employment descriptors were assessed. Medical records on a sample of the claims were reviewed to validate the diagnosis of OCTS. Age, gender, and occupation were available for less than 47% of the reported cases of OCTS. The majority (88%) of cases on whom medical record review was performed had a physician's diagnosis of carpal tunnel syndrome (CTS), and most of this group had confirmatory nerve conduction studies or electromyography. However, there were fundamental limitations to workers' compensation based disease surveillance in Massachusetts, including underascertainment of cases, potential ascertainment biases, delayed case reporting, limited access to specific diagnostic information, and incomplete and sometimes inaccurate information. These limitations are likely to be applicable in many, if not most, states and must be made clear in any analyses based on workers' compensation data. (C) 1994 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. UNIV MASSACHUSETTS,MED CTR,DEPT FAMILY & COMMUNITY MED,OCCUPAT HLTH PROGRAM,WORCESTER,MA 01605. MASSACHUSETTS DEPT PUBL HLTH,DIV OCCUPAT HLTH SURVEILLANCE,BOSTON,MA 02130. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114. RP KORRICK, SA (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,CHANNING LAB,180 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL07427]; NIEHS NIH HHS [ES00002]; PHS HHS [U60/CCU103010] NR 29 TC 18 Z9 18 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUN PY 1994 VL 25 IS 6 BP 837 EP 850 DI 10.1002/ajim.4700250608 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NK981 UT WOS:A1994NK98100007 PM 8067361 ER PT J AU PUGH, JA TULEY, MR BASU, S AF PUGH, JA TULEY, MR BASU, S TI SURVIVAL AMONG MEXICAN-AMERICANS, NON-HISPANIC WHITES, AND AFRICAN-AMERICANS WITH END-STAGE RENAL DISEASE - THE EMERGENCE OF A MINORITY PATTERN OF INCREASED INCIDENCE AND PROLONGED SURVIVAL SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE SURVIVAL; END-STAGE RENAL DISEASE; HISPANIC; MEXICAN-AMERICAN; MINORITIES ID RENAL-DISEASE; DIALYSIS; THERAPY C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV GEN INTERNAL MED,SAN ANTONIO,TX 78284. RP PUGH, JA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [1U01HS0739701]; NIDDK NIH HHS [DK38392] NR 17 TC 44 Z9 44 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUN PY 1994 VL 23 IS 6 BP 803 EP 807 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA NQ744 UT WOS:A1994NQ74400006 PM 8203362 ER PT J AU MILLER, MQ QUINNHURST, M AF MILLER, MQ QUINNHURST, M TI NEUROBEHAVIORAL ASSESSMENT OF HIGH-RISK INFANTS IN THE NEONATAL INTENSIVE-CARE UNIT SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE INFANT, LOW BIRTH WEIGHT; INFANT, NEWBORN ID BIRTH AB Neurobehavioral organization describes infants' abilities to organize themselves within their central nervous system maturation and environment. As part of infants' environment, caregivers can structure the environment to support infants' development. Care of the high-risk infant emphasizes support of infants' emerging neurobehavioral organization. This article describes the theoretical rationale of neurobehavioral organization, effect on the infant and family, and assessments available to the neonatal occupational therapist for use with high-risk infants. Information gained via neurobehavioral assessment can be used to engage parents in better understanding their infant's behaviors and interact at a level appropriate with their infant. C1 NW NEONATOL ASSOCIATES,SPOKANE,WA. DEACONESS MED CTR,INTENS CARE NURSERY,SPOKANE,WA. RP MILLER, MQ (reprint author), SACRED HEART MED CTR,101 W 8TH AVE,POB 2555,SPOKANE,WA 99220, USA. NR 30 TC 4 Z9 4 U1 0 U2 0 PU AMER OCCUPATION THERAPY ASSN PI ROCKVILLE PA 1383 PICCARD DRIVE PO BOX ROCKVILLE, MD 20850-4375 SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD JUN PY 1994 VL 48 IS 6 BP 506 EP 513 PG 8 WC Rehabilitation SC Rehabilitation GA NL350 UT WOS:A1994NL35000004 PM 7520667 ER PT J AU PODURI, A GEARING, M REBECK, GW MIRRA, SS TIGGES, J HYMAN, BT AF PODURI, A GEARING, M REBECK, GW MIRRA, SS TIGGES, J HYMAN, BT TI APOLIPOPROTEIN E4 AND BETA-AMYLOID IN SENILE PLAQUES AND CEREBRAL BLOOD-VESSELS OF AGED RHESUS-MONKEYS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID E MESSENGER-RNA; SPORADIC ALZHEIMERS-DISEASE; E CDNA; PROTEIN; ALLELE; IMMUNOREACTIVITY; EPSILON-4; DEPOSITS; SEQUENCE; CLONING AB Recent studies of late onset familial and sporadic Alzheimer's disease (AD) show a genetic disequilibrium between inheritance of the epsilon 4 allele of the apolipoprotein E (APoE) gene and development of AD. beta-Amyloid (alpha beta)-positive senile plaques and blood vessels in AD are immunoreactive for ApoE, suggesting that ApoE plays a role in amyloid deposition We examined the brains of nine rhesus monkeys (Macaca mulatta) to determine the immunohistochemical distribution of APoE and to investigate the association of ApoE with alpha beta in this species. Antibodies to APoE and alpha beta labeled senile plaques and vessels in the brains of aged monkeys, indicating cross-species homogeneity of the association of these two proteins. Polymerase chain reaction/ restriction enzyme analysis of the ApoE epsilon 3/epsilon 4 allelic site (residue 112) in the rhesus monkey revealed that the rhesus has an arginine at this site like the human epsilon 4 allele, the cynomolgus monkey, baboon, cow, pig, mouse, and rat but unlike the human epsilon 3 allele and the rabbit. These results emphasize the valu of aged nonhuman primates as animal models for alpha beta deposition and APoE4-alpha beta interactions in AD and aging. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. EMORY UNIV,SCH MED,VET AFFAIRS MED CTR,ATLANTA,GA. EMORY UNIV,SCH MED,DEPT PATHOL & LAB MED,ATLANTA,GA 30322. EMORY UNIV,DEPT ANAT & CELL BIOL,ATLANTA,GA 30322. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. FU NIA NIH HHS [AG00001, AG05598, AG10130] NR 29 TC 58 Z9 58 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 JUN PY 1994 VL 144 IS 6 BP 1183 EP 1187 PG 5 WC Pathology SC Pathology GA NQ324 UT WOS:A1994NQ32400008 PM 8203459 ER PT J AU KITTEN, AM HYMER, TK KATZ, MS AF KITTEN, AM HYMER, TK KATZ, MS TI BIDIRECTIONAL MODULATION OF PARATHYROID HORMONE-RESPONSIVE ADENYLYL-CYCLASE BY PROTEIN-KINASE-C SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PHORBOL ESTER; PARATHYROID HORMONE RECEPTOR; DIACYLGLYCEROL; G PROTEINS; OSTEOBLAST ID OSTEOBLAST-LIKE CELLS; CYCLIC-AMP PRODUCTION; INDUCED HOMOLOGOUS DESENSITIZATION; SIGNAL TRANSDUCTION SYSTEMS; OSTEOSARCOMA CELLS; PHORBOL ESTER; PTH RECEPTOR; SARCOMA CELLS; CAMP; STIMULATION AB The temporal pattern with which phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), modulates parathyroid hormone (PTH)-responsive adenylyl cyclase (AC) was evaluated in a clonal osteoblast-like cell line (UMR-106). Brief (less than or equal to 1 h) exposure of UMR-106 cells to PMA enhanced PTH simulation of AC, whereas more prolonged PMA treatment decreased the PTH response, with maximum inhibition occurring at less than or equal to 6 h. PMA treatment also resulted in initial activation followed by downregulation of PKC. Exposure of cells to 1,2-dioctanoyl-sn-glycerol, which activated but did not downregulate PKC, resulted in bidirectional modulation of PTH-responsive AC identical to that produced by PMA. Prolonged PMA exposure decreased PTH receptor number, as determined by radioligand binding studies, and reduced PTH receptor mRNA levels, assessed by Northern blot analysis. Forskolin activation of the catalytic subunit of AC was also decreased after prolonged PMA treatment. The results suggest that activation of PKC sequentially stimulates and then inhibits PTH responsiveness. Inhibition of the PTH response occurs by PKC actions exerted on the PTH receptor and the AC catalytic subunit. C1 AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. NR 33 TC 16 Z9 16 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 JUN PY 1994 VL 266 IS 6 BP E897 EP E904 PN 1 PG 8 WC Physiology SC Physiology GA NV809 UT WOS:A1994NV80900045 PM 8023920 ER PT J AU VOGT, JA FISCHMAN, AJ KEMPF, M YU, YM TOMPKINS, RG BURKE, JF AF VOGT, JA FISCHMAN, AJ KEMPF, M YU, YM TOMPKINS, RG BURKE, JF TI A GENERAL-MODEL FOR ANALYSIS OF THE TRICARBOXYLIC-ACID CYCLE WITH USE OF [C-13]GLUTAMATE ISOTOPOMER MEASUREMENTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE STEADY-STATE MODELING; C-13 NUCLEAR MAGNETIC RESONANCE ID QUANTITATIVE-ANALYSIS; METABOLIC PATHWAYS; GLYCOGEN REPLETION; KREBS CYCLE; NMR; C-13; LIVER; SPECTROSCOPY; INVIVO; HEART AB A generalized steady-state model was developed for determining tricarboxylic acid cycle fractional fluxes from C-13 nuclear magnetic resonance (NMR) data. The model relates the measured mole fractions of [C-13]glutamate isotopomers to the fractional fluxes and predicted mole fractions of isotopomers of oxaloacetate (OAA) and acetyl-CoA. This model includes cycling between OAA and fumarate. Fractional fluxes are determined by fitting the model equations to NMR parameters by use of nonlinear least squares. Although only fractional fluxes can be determined from C-13-NMR data, when they are combined with mass spectroscopic measurements, absolute values can he derived. A specific metabolic system represented by published C-13-NMR data from extracts of hearts perfused with [C-13]acetate, [C-13]pyruvate (PYR), and [C-13]acetate plus [C-13]PYR was used to test the model. The intensities of predicted C-13-NMR splitting patterns were compared with observed values, and there was excellent agreement between observed and predicted signal intensities. With this model, important physiological parameters, including the OAA-derived fraction of inflow to PYR, PYR-derived fraction of inflow to acetyl-CoA, citrate-derived fraction of inflow to OAA, and PYR-derived fraction of inflow to OAA, can be determined. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SHRINERS BURNS INST,DEPT SURG,SURG SERV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. NR 17 TC 10 Z9 10 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 JUN PY 1994 VL 266 IS 6 BP E1012 EP E1022 PN 1 PG 11 WC Physiology SC Physiology GA NV809 UT WOS:A1994NV80900059 ER PT J AU SABOLIC, I BROWN, D VERBAVATZ, JM KLEINMAN, J AF SABOLIC, I BROWN, D VERBAVATZ, JM KLEINMAN, J TI H+-ATPASES OF RENAL CORTICAL AND MEDULLARY ENDOSOMES ARE DIFFERENTIALLY SENSITIVE TO SCH-28080 AND OMEPRAZOLE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ADENOSINE-TRIPHOSPHATASE INHIBITORS; RAT KIDNEY; VACUOLAR HYDROGEN-ADENOSINE-TRIPHOSPHATASE; HYDROGEN-POTASSIUM-ADENOSINE-TRIPHOSPHATASE ID PROTON-PUMPING ATPASE; COLLECTING DUCT; ADENOSINE-TRIPHOSPHATASE; RAT-KIDNEY; K-ATPASE; ENDOCYTOTIC VESICLES; INTERCALATED CELLS; PROXIMAL TUBULE; DISTAL NEPHRON; SECRETION AB Adenosinetriphosphatase (ATPase) activity stimulated by K+ and inhibited by Sch-28080 (SCH), omeprazole (OME), and vanadate has been measured in microsomes from mammalian renal medulla and attributed to a kidney isoform of the H+-K+-ATPase. To determine whether the H+-K+-ATPase inhibitors could also inhibit the vacuolar (V)-type H+-adenosinetriphosphatase (H+-ATPase, i.e., HC pump) in mammalian intracellular vesicles, we examined their effects on bafilomycin-sensitive acidification in renal cortical vesicles (CEV) and medullary endocytic vesicles (MEV). Rats were injected with fluorescein isothiocya nate-labeled dextran, and labeled endosomes were enriched from kidney tissue homogenates by differential and Percoll density gradient centrifugation. In the CEV, the V-type H+ pump was inhibited 25% by SCH and 30% by OME (100 mu M each). Whereas the inhibition by OME was concentration and time dependent, the inhibition by SCH was only concentration dependent. Inhibition by these compounds was similar in the presence of 50 mM K+ (in = out) and in the complete absence of K+, thus ruling out a significant involvement of H+-K+-ATPase-mediated acidification. Inhibition, however, was not observed with 10 mu M SCH and OME. The sensitivity of the V-type H+ pump to 100 mu M SCH and OME in CEV was confirmed by the comparable inhibitions of intravesicular acidification observed in acridine orange fluorescence quench studies and by inhibition of P-i liberation in an ATPase assay. We also found that the V-type H+ pump in isolated rat liver endosomes is sensitive to 100 mu M SCH and OME to a similar degree. In the MEV, acidification was only weakly affected by 100 mu M SCH and OME, thus suggesting that H+-ATPases in endosomes from cortical and medullary tubules are different, possibly due to a previously described selective expression of subunit isoforms. Our finding indicates the importance of using low concentrations (<10 mu M) of OME and SCH in studies of H+-K+-ATPase in nongastric tissues to avoid misinterpretation of the data due to nonspecific inhibition of V-type H+-ATPases. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. VET ADM MED CTR,MILWAUKEE,WI 53295. MED COLL WISCONSIN,MILWAUKEE,WI 53295. FU NIDDK NIH HHS [DK-42956] NR 29 TC 38 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 JUN PY 1994 VL 266 IS 6 BP F868 EP F877 PN 2 PG 10 WC Physiology SC Physiology GA NV810 UT WOS:A1994NV81000096 PM 7517642 ER PT J AU MARDER, SR MEIBACH, RC AF MARDER, SR MEIBACH, RC TI RISPERIDONE IN THE TREATMENT OF SCHIZOPHRENIA SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NEGATIVE SYNDROME SCALE; RITANSERIN R-55667; SEROTONIN-S2; HALOPERIDOL; ANTAGONIST; EFFICACY; PLACEBO; SAFETY AB Objective: The purpose of this study was to investigate the safety and efficacy of risperidone in the treatment of schizophrenic Patients and determine its optimal dose. Method: This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States. Patients were randomly assigned to 8 weeks' treatment with placebo, one Of four doses of risperidone (2, 6, 10, or 16 mg), or 20 mg of haloperidol daily. Results: Clinical improvement (20% reduction in total scores on the Positive and Negative Syndrome Scale for Schizophrenia) at the study end point was shown by 35% of the patients receiving 2 mg of risperidone, 57% receiving 6 mg, 40% receiving 10 mg, and 51% receiving 16 mg; and by 30% receiving haloperidol and 22% receiving placebo. Statistically significant differences in clinical improvement were found between 6 and 16 mg of risperidone versus placebo and versus haloperidol. Positive symptom scores were significantly lower after 6, 10, and 16 mg of risperidone and 20 mg of haloperidol than placebo; negative symptom scores, however, were reduced significantly, compared with placebo, only after 6 and 16 mg of risperidone. The incidence of extrapyramidal side effects (measured by the Extrapyramidal Symptom Rating Scale) was significantly higher in patients treated with 16 mg of risperidone or 20 mg of haloperidol than placebo. The results indicate that the optimal daily dose of risperidone for most schizophrenic patients in this study was 6 mg; this dose was as effective as 16 mg, and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving Placebo. Conclusions: Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia. C1 JANSSEN RES FDN,TITUSVILLE,NJ. RP MARDER, SR (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,BRENTWOOD DIV,PSYCHIAT SERV 116A,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 29 TC 1045 Z9 1070 U1 11 U2 51 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 JUN PY 1994 VL 151 IS 6 BP 825 EP 835 PG 11 WC Psychiatry SC Psychiatry GA NN755 UT WOS:A1994NN75500006 PM 7514366 ER PT J AU THOMPSON, BT SPENCE, CR JANSSENS, SP JOSEPH, PM HALES, CA AF THOMPSON, BT SPENCE, CR JANSSENS, SP JOSEPH, PM HALES, CA TI INHIBITION OF HYPOXIC PULMONARY-HYPERTENSION BY HEPARINS OF DIFFERING IN-VITRO ANTIPROLIFERATIVE POTENCY SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID SMOOTH-MUSCLE CELLS; STRUCTURAL DETERMINANTS; PROLIFERATION; ARTERIES; CAPACITY AB Heparin inhibits smooth-muscle cell (SMC) growth in vitro and inhibits the development of hypoxic pulmonary hypertension and Vascular remodeling in vivo. We wondered whether preparations of heparin with different antiproliferative potency in vitro would differ in their ability to inhibit the development of hypoxic pulmonary hypertension in vivo. Two such heparins, a weakly antiproliferative lot of Elkins-Sinn (E-S) (% inhibition of SMC growth at 10 mu g/ml = 13 +/- 9% [mean +/- SEM, n = 24]) and a more active lot from Upjohn (UJ) (% inhibition = 71 +/- 12% [n = 12, p < 0.05 versus E-S]I), were infused subcutaneously (300 U.S.P. units/day; E-S 300 versus UJ 300) via an osmotic pump into guinea pigs exposed to hypoxia (10% O-2) for 10 d, after which pulmonary artery pressure (PAP; mm Hg) and cardiac index (Cl; ml/min/kg) were measured in room air. Hypoxic controls (HC) received saline. PAP increased from 11 +/- 1 mm Hg in normoxic controls (NC) (n = 5) to 24 +/- 1 mm Hg in HC (n = 8, p < 0.05). The PAP was lower in the E-S 300 (21 +/- 1; n = 7, p < 0.05 versus HC and NC) and even lower in the UJ 300-treated group (18 +/- 0.5; n - 7, p < 0.05 versus HC and NC). Total pulmonary vascular resistance (TPR; mm Hg/ml/min/kg) increased significantly from 0.038 a 0.002 in NC to 0.076 +/- 0.003 (p < 0.05) in HC. There was no difference in TPR between the HC and the E-S 300-treated group. However, UJ 300 significantly reduced the TPR to 0.057 +/- 0.003 (p < 0.05 versus HC and NC). The medial thickness (as a percent of vessel diameter) of arteries landmarked to alveolar ducts (AD) and to terminal bronchioles (TB) increased significantly with hypoxia. Medial thickening was not affected by E-S 300, but was significantly reduced by UJ 300. We conclude that heparins not only differ in their antiproliferative activity in vitro, but also in their ability to inhibit the development of hypoxic pulmonary hypertension and remodeling in vivo. Heparin may inhibit chronic hypoxic vascular remodeling by inhibiting SMC growth in vivo, and in vitro assessment of antiproliferative potency appears to predict the in vivo response. RP THOMPSON, BT (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,PULM & CRIT CARE UNIT,BOSTON,MA 02114, USA. FU FIC NIH HHS [1F05TW04379-1]; NHLBI NIH HHS [HL 07354, HL 39150] NR 22 TC 34 Z9 34 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN PY 1994 VL 149 IS 6 BP 1512 EP 1517 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NQ971 UT WOS:A1994NQ97100020 PM 8004307 ER PT J AU SCHULZE, ES MATTIA, AR CHEW, FS AF SCHULZE, ES MATTIA, AR CHEW, FS TI BRONCHIOLOALVEOLAR CARCINOMA SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Note C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. NR 2 TC 4 Z9 4 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 JUN PY 1994 VL 162 IS 6 BP 1294 EP 1294 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NN228 UT WOS:A1994NN22800004 PM 8191983 ER PT J AU HAHN, PF LEE, MJ GAZELLE, GS FORMAN, BH MUELLER, PR AF HAHN, PF LEE, MJ GAZELLE, GS FORMAN, BH MUELLER, PR TI A SIMPLIFIED HYPERCARD DATA-BASE FOR PATIENT-MANAGEMENT IN AN INTERVENTIONAL PRACTICE - EXPERIENCE WITH MORE THAN 4000 CASES SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. Tracking of interventional radiology procedures is essential for patients' care, follow-up, and quality management, as well as for fellowship training and accreditation. Computer data-base systems that require time-consuming data entry are difficult to use in a practice that performs 1500 abdominal interventional procedures each year while concurrently doing diagnostic imaging. We proposed that a data base updated with data from existing sources and furnishing information used daily in patient management could be maintained by the radiologists it serves. MATERIALS AND METHODS. We developed a data base to track abdominal interventional radiology cases by using the HyperCard application program running on Macintosh personal computers. For each procedure, one card is entered into the Current Cases stack, which prints a daily log including new patients, those with management issues, and pending biopsy results. Cards for inactive patients are automatically compressed and transferred to a second stack for permanent archive. The latter can be queried to identify individual patients, to list complications, and for research. RESULTS. In continuous use for 3 years, the system has logged 4322 procedures in 2394 patients. Ninety percent of data entry is by a secretary. The daily log serves as the focus for the case conference at the close of work, when errors are corrected and specific comments entered. Three independent searches for specific types of procedures have failed to identify excluded cases. CONCLUSION. Easy data entry and error correction, together with useful information provided daily by the data base, are features of the system that promote its consistent use. C1 HAHNEMANN UNIV,INFORMAT SERV,PHILADELPHIA,PA 19102. RP HAHN, PF (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 9 TC 8 Z9 8 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 JUN PY 1994 VL 162 IS 6 BP 1443 EP 1446 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NN228 UT WOS:A1994NN22800037 PM 8192015 ER PT J AU WILENS, TE SALEY, P RENNER, JA OKEEFE, J AF WILENS, TE SALEY, P RENNER, JA OKEEFE, J TI A PUBLIC DUAL-DIAGNOSIS DETOXIFICATION UNIT .3. SHORT-TERM EFFICACY OF TREATMENT SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SUBSTANCE-ABUSE; MENTALLY-ILL; LOS-ANGELES; INNER-CITY; DRUG-ABUSE; DISORDERS; ALCOHOL; SCHIZOPHRENIA; PATTERNS; HEALTH AB Despite the frequency of alcohol and drug dependence in mentally ill people, data are not readily available on the detoxification and acute stabilization of psychiatric symptoms in this group. The authors bate previous by reported on a public dual-diagnosis treatment model for homeless or homeless-prone patients. They now report on a pilot prospective study investigating the efficacy of this short-term treatment in stabilizing psychiatric symptoms. The Brief Psychiatric Rating Scale (BPRS) and Clinicians' Global Improvement (CGI) and Severity Scale (CGS) were used to assess treatment stabilization in alcohol-dependent subjects referred with (n = 12) or without psychiatric disorders (n = 12). The psychiatrically referred group bad significantly more psychiatric impairment and symptoms at admission than control subjects, but both groups showed similar progressive improvement in symptoms on hospitalization Days 2, 4, and 6 as assessed by both the BPRS and CGI (23% reduction by Day 6, all Ps < 0.001). These findings indicate that a public dual-diagnosis detoxification unit appears effective in stabilizing psychiatric symptoms in this group of psychiatrically referred, alcohol-dependent patients. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 34 TC 2 Z9 2 U1 4 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SUM PY 1994 VL 3 IS 3 BP 194 EP 203 PG 10 WC Substance Abuse SC Substance Abuse GA NY914 UT WOS:A1994NY91400002 ER PT J AU HYLEK, EM SINGER, DE AF HYLEK, EM SINGER, DE TI RISK-FACTORS FAR INTRACRANIAL HEMORRHAGE IN OUTPATIENTS TAKING WARFARIN SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ORAL ANTICOAGULANT-THERAPY; CEREBRAL AMYLOID ANGIOPATHY; ATRIAL-FIBRILLATION; INTRACEREBRAL HEMATOMAS; STROKE; COMPLICATIONS; PREVENTION; HYPERTENSION; INTENSITIES; POPULATION AB Objective: To explore the rational use of anticoagulants, especially among the elderly, balancing antithrombotic efficacy and risk for hemorrhage. Previous prospective studies have not provided powerful assessments of risk factors for intracranial hemorrhage, the dominant complication in reversing the anticoagulant decision. Design: Case-control analysis. Setting: A large general hospital and its anticoagulant therapy unit. Patients: 121 consecutive adult patients taking warfarin who were hospitalized with intracranial hemorrhage were each matched to three contemporaneous controls randomly selected from among outpatients managed by our hospital anticoagulant therapy unit. Results: 77 patients had intracerebral hemorrhage (46% fatal) and 44 had subdural hemorrhage (20% fatal). The prothrombin time ratio (PTR) was the dominant risk factor for intracranial hemorrhage. For each 0.5 increase in PTR over the entire range, the risk for intracerebral hemorrhage doubled (odds ratio, 2.1; 95% CI, 1.4 to 2.9). For subdural hemorrhage, the risk was unchanged over the PTR range from 1.0 to 2.0 but rose dramatically above a PTR of 2.0 (approximate international normalized ratio, 4.0). Age was the only other significant independent risk factor for subdural hemorrhage (odds ratio, 2.0 per decade; CI, 1.3 to 3.1). For intracerebral hemorrhage, age was of borderline significance (odds ratio, 1.3 per decade; CI, 1.0 to 1.6) after controlling for PTR and the two other independent risk factors: history of cerebrovascular disease (odds ratio, 3.1; CI, 1.7 to 5.6) and presence of a prosthetic heart valve (odds ratio, 2.8; CI, 1.3 to 5.8). Conclusions: The results emphasize the importance of maintaining the prothrombin time ratios under 2.0 and the need for especially careful use of warfarin in the elderly. RP HYLEK, EM (reprint author), MASSACHUSETTS GEN HOSP,GEN INTERNAL MED UNIT,BULFINCH 1,BOSTON,MA 02114, USA. NR 37 TC 646 Z9 663 U1 0 U2 8 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 JUN 1 PY 1994 VL 120 IS 11 BP 897 EP 902 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NN110 UT WOS:A1994NN11000001 PM 8172435 ER PT J AU WIRGUIN, I SUTURKOVAMILOSEVIC, L DELLALATTA, P FISHER, T BROWN, RH LATOV, N AF WIRGUIN, I SUTURKOVAMILOSEVIC, L DELLALATTA, P FISHER, T BROWN, RH LATOV, N TI MONOCLONAL IGM ANTIBODIES TO GM1 AND ASIALO-GM1 IN CHRONIC NEUROPATHIES CROSS-REACT WITH CAMPYLOBACTER-JEJUNI LIPOPOLYSACCHARIDES SO ANNALS OF NEUROLOGY LA English DT Article ID GUILLAIN-BARRE-SYNDROME; ANTI-GM1 ANTIBODIES; CHEMICAL STRUCTURES; PERIPHERAL-NERVE; POLYNEUROPATHY; SEROTYPE; PURIFICATION; GANGLIOSIDES; INFECTION; ANTIGENS AB We tested monoclonal IgM anti-GM1 and asialo-GM1 antibodies from 6 patients with chronic motor neuropathies for binding to lipopolysaccharides (LPS) from three strains of Campylobacter jejuni. Four of the 6 patients showed strong reactivity with LPS from at least one of the three C. jejuni strains tested as shown by enzyme-linked immunosorbent assay or western blot. Preabsorption with GM1 or asialo-GM1, of blocking with cholera toxin, prevented antibody binding to LPS. These studies indicate that human anti-GM1 or anti-asialo-GM1 antibodies cross-react with LPS from certain strains of C. jejuni, and that bacterial LPS might provide antigenic stimuli for the activation of B cells expressing anti-GM1 antibodies. C1 COLUMBIA UNIV,COLL PHYS & SURG,DEPT NEUROL,NEW YORK,NY 10032. COLUMBIA UNIV,COLL PHYS & SURG,DEPT CLIN MICROBIOL,NEW YORK,NY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA. OI Suturkova, Ljubica/0000-0003-0818-1961 FU PHS HHS [WS11766] NR 36 TC 55 Z9 55 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 JUN PY 1994 VL 35 IS 6 BP 698 EP 703 DI 10.1002/ana.410350610 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NQ973 UT WOS:A1994NQ97300009 PM 8210226 ER PT J AU HANDFORTH, A FINCH, DM PETERS, R TAN, AM TREIMAN, DM AF HANDFORTH, A FINCH, DM PETERS, R TAN, AM TREIMAN, DM TI INTERICTAL SPIKING INCREASES 2-DEOXY(C-14)GLUCOSE UPTAKE AND C-FOS-LIKE REACTIVITY SO ANNALS OF NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-UTILIZATION; STATUS EPILEPTICUS; PARTIAL SEIZURES; PARTIAL EPILEPSY; MESSENGER-RNA; DENTATE GYRUS; RAT-BRAIN; EXPRESSION; STIMULATION AB Although interictal spikes are thought to share pathophysiological mechanisms with partial-onset seizure discharges, positron emission tomographic studies of the interictal state have paradoxically shown focal hypometabolism whereas seizures produce hypermetabolism To address this question, we performed functional mapping studies in an interictal spiking model in the rat. Recording screw electrodes were inserted through the skull bone so as to depress underlying cortex. Interictal spiking was subsequently induced by systemic administration of bicuculline methiodide. 2-deoxy[C-14]glucose studies revealed increased glucose utilization in superficial and middle cortical layers at spiking screw sites. Nonspiking screw sites in the same animals and in controls did not show increased uptake. Convulsive seizures caused additional 2-deoxy[C-14]glucose uptake at screw sites and in widespread forebrain areas. c-fos immunoreactivity occurred in superficial cortex at interictal spiking, but not nonspiking, sites. Convulsive seizures induced widespread forebrain c-fos immunoreactivity. These data suggest interictal epileptiform activity occurs in cells adjacent to cortical injury; these activate deeper layers via local connections. Interictal and ictal epileptiform states share common mechanisms, as both induce glucose hypermetabolism and immediate-early gene product activation. Possible reasons for failure to detect hypermetabolism in interictal human subjects are discussed. C1 W LOS ANGELES DEPT VET AFFAIRS MED CTR,RES SERV,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT NEUROL,LOS ANGELES,CA 90024. RP HANDFORTH, A (reprint author), DEPT VET AFFAIRS MED CTR,W LOS ANGELES WADSWORTH DIV,NEUROL SERV,SAWTELLE & WILSHIRE BLVDS,LOS ANGELES,CA 90073, USA. FU NINDS NIH HHS [NS 16721] NR 28 TC 23 Z9 23 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUN PY 1994 VL 35 IS 6 BP 724 EP 731 DI 10.1002/ana.410350614 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NQ973 UT WOS:A1994NQ97300013 PM 8210230 ER PT J AU ICHIMIYA, I ADAMS, JC KIMURA, RS AF ICHIMIYA, I ADAMS, JC KIMURA, RS TI CHANGES IN IMMUNOSTAINING OF COCHLEAS WITH EXPERIMENTALLY-INDUCED ENDOLYMPHATIC HYDROPS SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE ADENOSINE-TRIPHOSPHATASE; ENDOLYMPHATIC HYDROPS; GAP JUNCTION; GUINEA PIG; IMMUNOHISTOCHEMISTRY; SPIRAL LIGAMENT ID INNER-EAR; ALDEHYDE DEHYDROGENASE; STRIA VASCULARIS; ION-TRANSPORT; KIDNEY; LOCALIZATION; FIBROCYTES; CELLS AB Cochleas with experimentally induced endolymphatic hydrops were immunostained for Na+,K+-ATPase, intracellular Ca++-ATPase, carbonic anhydrase, aldehyde dehydrogenase, calcium-binding proteins, vimentin, and the gap junction protein, connexin 26. No changes in immunostaining of hydropic ears were observed 1 week after blockage of the endolymphatic duct. Two weeks to 1 month after the operation, immunostaining of type I fibrocytes in the spiral ligament, which are positive for all but Na+,K+-ATPase, was slightly decreased on the operated side. These changes became more pronounced 3 months after the operation. However, staining for Na+,K+-ATPase of the stria vascularis and of type II fibrocytes of the spiral ligament was not reduced until 6 months postoperative. The reduction of enzymes and other cell constituents that may be involved in ion balance of cochlear fluids indicates that cells in the spiral ligament play an important role in cochlear homeostasis and that they merit further study in animal and human otopathology. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. OITA MED UNIV,DEPT OTOLARYNGOL,OITA,JAPAN. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. FU NIDCD NIH HHS [R01 DC00073] NR 30 TC 50 Z9 50 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 JUN PY 1994 VL 103 IS 6 BP 457 EP 468 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA NQ978 UT WOS:A1994NQ97800007 PM 8203812 ER PT J AU INOUE, Y COPELAND, EM SOUBA, WW AF INOUE, Y COPELAND, EM SOUBA, WW TI GROWTH-HORMONE ENHANCES AMINO-ACID-UPTAKE BY THE HUMAN SMALL-INTESTINE SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 105th Annual Scientific Session of the Southern-Surgical-Association CY DEC 05-08, 1993 CL HOT SPRINGS, VA SP SO SURG ASSOC ID NUTRIENT TRANSPORTERS; NUTRITION; GLUTAMINE; CELLS; GAIN AB Objective The effects of growth hormone (GH) on the luminal transport of amino acids and glucose by the human small intestine were investigated. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. UNIV FLORIDA,COLL MED,DEPT SURG,DIV SURG ONCOL,GAINESVILLE,FL. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA 45327] NR 19 TC 76 Z9 77 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD JUN PY 1994 VL 219 IS 6 BP 715 EP 724 DI 10.1097/00000658-199406000-00016 PG 10 WC Surgery SC Surgery GA NQ777 UT WOS:A1994NQ77700016 PM 8203982 ER PT J AU BERENGUER, J ALI, NM ALLENDE, MC LEE, J GARRETT, K BATTAGLIA, S PISCITELLI, SC RINALDI, MG PIZZO, PA WALSH, TJ AF BERENGUER, J ALI, NM ALLENDE, MC LEE, J GARRETT, K BATTAGLIA, S PISCITELLI, SC RINALDI, MG PIZZO, PA WALSH, TJ TI ITRACONAZOLE FOR EXPERIMENTAL PULMONARY ASPERGILLOSIS - COMPARISON WITH AMPHOTERICIN-B, INTERACTION WITH CYCLOSPORINE-A, AND CORRELATION BETWEEN THERAPEUTIC RESPONSE AND ITRACONAZOLE CONCENTRATIONS IN PLASMA SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE ASPERGILLOSIS; SYSTEMIC MYCOSES; ANTIFUNGAL; INVITRO; CRYPTOCOCCOSIS; AZOLES; PHARMACOKINETICS; INVIVO AB Itraconazole and amphotericin B were compared by using a newly developed model of invasive pulmonary aspergillosis in rabbits immunosuppressed with methylprednisolone and cyclosporin A (CsA). Both itraconazole at 40 mg/kg (given orally) and amphotericin B at 1 mg/kg (given intravenously) had in vivo antifungal activity in comparison with controls, At these dosages, amphotericin B was more effective than itraconazole in reducing the tissue burden (log(10) CFU per gram) of Aspergillus fumigatus (P < 0.05) and the number of pulmonary lesions (P < 0.01). However, there was considerable variation in the near-peak concentrations of itraconazole in plasma (median, 4.15 mu g/ml; range, <0.5 to 16.8 mu g/ml) and a strong inverse correlation between concentrations of itraconazole in plasma and the tissue burden of A. fumigatus. An inhibitory sigmoid maximum-effect model predicted a significant pharmacodynamic relationship (r = 0.87, P < 0.001) between itraconazole concentrations in plasma and antifungal activity as a function of the tissue burden of A, fumigatus. This model demonstrated that levels in plasma of greater than 6 mu g/ml were associated with a significantly greater antifungal effect. Levels in plasma of less than 6 mu g/ml were associated with a rapid decline in the antifungal effect. Itraconazole, in comparison with amphotericin B, caused a twofold elevation of CsA levels (P < 0.01) but was less nephrotoxic (P < 0.01). This study of experimental pulmonary aspergillosis demonstrated that amphotericin B at 1 mg/kg/day was more active but more nephrotoxic than itraconazole at 40 mg/kg/day, that itraconazole increased concentrations of CsA in plasma, and that the antifungal activity of itraconazole strongly correlated with concentrations in plasma in an inhibitory sigmoid maximum-effect model. These findings further indicate the importance of monitoring concentrations of itraconazole in plasma as a guide to increasing dosage, improving bioavailability, and optimizing antifungal efficacy in the treatment of invasive pulmonary aspergillosis. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT PHARM,PHARMACOKINET RES LAB,BETHESDA,MD 20892. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78229. AUDIE L MURPHY MEM VET ADM MED CTR,LAB SERV,SAN ANTONIO,TX 78221. OI Berenguer, Juan/0000-0001-8541-8200 NR 32 TC 60 Z9 61 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 JUN PY 1994 VL 38 IS 6 BP 1303 EP 1308 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NN770 UT WOS:A1994NN77000015 PM 8092829 ER PT J AU NG, EYW TRUCKSIS, M HOOPER, DC AF NG, EYW TRUCKSIS, M HOOPER, DC TI QUINOLONE RESISTANCE MEDIATED BY NORA - PHYSIOLOGICAL CHARACTERIZATION AND RELATIONSHIP TO FLQB, A QUINOLONE RESISTANCE LOCUS ON THE STAPHYLOCOCCUS-AUREUS CHROMOSOME SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MULTIDRUG EFFLUX TRANSPORTER; ESCHERICHIA-COLI; FLUOROQUINOLONE RESISTANCE; ACTIVE EFFLUX; GEL-ELECTROPHORESIS; DETERMINING REGION; BACILLUS-SUBTILIS; DNA; PROTEIN; GENE AB We identified a quinolone resistance locus, flqB, linked to transposon insertion Omega 1108 and fus on the SmaI D fragment of the Staphylococcus aureus NCTC 8325 chromosome, the same fragment that contains the norA. gene. S. aureus norA cloned from flqB and flqB(+) strains in Escherichia coli differed only in a single nucleotide in the putative promoter region. There was no detectable change in the number of copies of norA on the chromosomes of flqB Strains, but they had increased levels of norA transcripts. Cloned norA produced resistance to norfloxacin and other hydrophilic quinolones and reduced norfloxacin accumulation in intact cells that was energy dependent, suggesting active drug efflux: as the mechanism of resistance. Drug efflux was studied by measurement of norfloxacin uptake into everted inner membrane vesicles prepared from norA-containing E. coli cells. Vesicles exhibited norfloxacin uptake after the addition of lactate or NADH, and this uptake was abolished by carbonyl cyanide m-chlorophenylhydrazone and nigericin but not valinomycin, indicating that it was linked to the pH gradient across the cell membrane. Norfloxacin uptake into vesicles was also saturable, with an apparent K-m of 6 mu M, a concentration between those that inhibit the growth of flqB and flqB(+) S. aureus cells, indicating that drug uptake is mediated by a carrier with a high apparent affinity for norfloxacin. Ciprofloxacin and ofloxacin competitively inhibited norfloxacin uptake into vesicles. Reserpine, which inhibits the multidrug efflux mediated by the bmr gene of Bacillus subtilis, which is similar to norA, abolished norfloxacin uptake into vesicles as well as the norfloxacin resistance of an flqB mutant, suggesting a potential means for circumventing quinolone resistance as a result of drug efflux in S. aureus. These findings indicate that the chromosomal flqB resistance locus is associated with increased levels of expression of norA and strongly suggest that the NorA protein itself functions as a drug transporter that is coupled to the proton gradient across the cell membrane. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,MED SERV,BOSTON,MA 02114. FU NIAID NIH HHS [AI23988] NR 40 TC 150 Z9 153 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUN PY 1994 VL 38 IS 6 BP 1345 EP 1355 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NN770 UT WOS:A1994NN77000022 PM 8092836 ER PT J AU CHANG, TKH GONZALEZ, FJ WAXMAN, DJ AF CHANG, TKH GONZALEZ, FJ WAXMAN, DJ TI EVALUATION OF TRIACETYLOLEANDOMYCIN, ALPHA-NAPHTHOFLAVONE AND DIETHYLDITHIOCARBAMATE AS SELECTIVE CHEMICAL PROBES FOR INHIBITION OF HUMAN CYTOCHROMES P450 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HUMAN-LIVER-MICROSOMES; CDNA-DIRECTED EXPRESSION; SACCHAROMYCES-CEREVISIAE; THEOPHYLLINE METABOLISM; COUMARIN 7-HYDROXYLASE; RECOVERING ALCOHOLICS; ENZYMES; OXIDATION; RAT; IDENTIFICATION AB A variety of chemicals, including triacetyloleandomycin (TAO), alpha-naphthoflavone (ANF), and diethyldithiocarbamate (DDC), are widely used as inhibitory probes for select individual human cytochrome P450 (CYP) enzymes, despite the fact that the selectivity of these inhibitors has not been rigorously evaluated. In the present study we take advantage of recent advances in cDNA-directed human P450 expression to evaluate directly the P450 form selectivity of TAO, ANF, and DDC, using a panel of 10 individual cDNA-expressed human P450s. Under experimental conditions known to yield maximal TAO complexation with P450 hemoproteins, TAO (20 mu M) inhibited the catalytic activity of expressed CYPs 3A3, 3A4, and 3A5, whereas it did not affect CYPs 1A1, 1A2, 2A6, 2B6, 2C8, 2C9, or 2E1 activity. ANF inhibited not only CYPs 1A1 and 1A2 (IC50 = 0.4-0.5 mu M), but it was also similarly effective against CYPs 2C8 and 2C9. Increasing the concentration of ANF to 10 mu M led to inhibition of CYP2A6 and CYP2B6. Although a previous study suggested that DDC is a selective inhibitor of CYP2E1, the present investigation shows that at concentrations required to inhibit CYP2E1 (IC50 approximate to 125 mu M when preincubated with NADPH), DDC also inhibited CYPs 1A1, 1A2, 2A6, 2B6, 2C8, 3A3, and 3A4. Decreasing the concentration of DDC to 10 mu M, however, led to inhibition of CYP2A6 (65% inhibition) and CYP2B6 (50% inhibition), but none of the other p450s examined, including CYP2E1. Overall, these results establish that (a) TAO is a selective inhibitor of the human CYP3A subfamily; (b) ANF potently inhibits CYP2C8 and CYP2C9, in addition to CYPs 1A1 and 1A2; and (c) DDC cannot be employed as a diagnostic inhibitory probe for CYP2E1. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-49248] NR 46 TC 252 Z9 252 U1 4 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN PY 1994 VL 311 IS 2 BP 437 EP 442 DI 10.1006/abbi.1994.1259 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NP638 UT WOS:A1994NP63800033 PM 8203907 ER PT J AU ARBISER, JL GROSSMAN, K KAYE, E ARNDT, KA AF ARBISER, JL GROSSMAN, K KAYE, E ARNDT, KA TI USE OF SHORT-COURSE CLASS-1 TOPICAL GLUCOCORTICOID UNDER OCCLUSION FOR THE RAPID CONTROL OF ERYTHRODERMIC PSORIASIS SO ARCHIVES OF DERMATOLOGY LA English DT Note ID BETAMETHASONE DIPROPIONATE C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BETH ISRAEL HOSP,BOSTON,MA 02215. RP ARBISER, JL (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA, USA. NR 8 TC 8 Z9 8 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 JUN PY 1994 VL 130 IS 6 BP 704 EP 706 DI 10.1001/archderm.130.6.704 PG 3 WC Dermatology SC Dermatology GA NQ995 UT WOS:A1994NQ99500002 PM 8002640 ER PT J AU ODENHEIMER, G FUNKENSTEIN, HH BECKETT, L CHOWN, M PILGRIM, D EVANS, D ALBERT, M AF ODENHEIMER, G FUNKENSTEIN, HH BECKETT, L CHOWN, M PILGRIM, D EVANS, D ALBERT, M TI COMPARISON OF NEUROLOGIC CHANGES IN SUCCESSFULLY AGING PERSONS VS THE TOTAL AGING POPULATION SO ARCHIVES OF NEUROLOGY LA English DT Article ID DIAGNOSED ALZHEIMERS-DISEASE; OLD-AGE; COMMUNITY; PREVALENCE; STRENGTH; SIGNS AB Objective: To determine age-related changes in neurologic function in the general population. Design: To administer a neurologic examination to participants in such a way that it is possible to calculate the proportion of elderly persons in the population with each abnormal finding and the proportion of persons with each finding but without evidence of the medical and neurologic diseases likely to produce neurologic abnormalities (eg, stroke and diabetes). Setting: Individuals were selected from a community-dwelling population. Participants: A stratified random sample of 467 persons aged 65 years and older were evaluated. Results: Many neurologic abnormalities are increasingly common with advancing age and are present in a substantial portion of the elderly population. The prevalence of abnormal neurologic findings not attributable to disease, however, is substantially lower, typically one half to one third the total prevalence. Moreover, the increase with age in the prevalence of abnormal neurologic findings not attributable to major disease varies substantially among the different measures. Conclusions: Primitive reflexes and measures of gait show statistically significant increases with age in multiple measurement domains, suggesting a selective age-related vulnerability. C1 BROCKTON W ROXBURY VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,BOSTON,MA. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA. FU NIA NIH HHS [R01-AG05362, N01-AG12106, AG06789] NR 38 TC 57 Z9 58 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 JUN PY 1994 VL 51 IS 6 BP 573 EP 580 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA NQ146 UT WOS:A1994NQ14600007 PM 8198468 ER PT J AU ORLANDI, A EHRLICH, HP ROPRAZ, P SPAGNOLI, LG GABBIANI, G AF ORLANDI, A EHRLICH, HP ROPRAZ, P SPAGNOLI, LG GABBIANI, G TI RAT AORTIC SMOOTH-MUSCLE CELLS ISOLATED FROM DIFFERENT LAYERS AND AT DIFFERENT TIMES AFTER ENDOTHELIAL DENUDATION SHOW DISTINCT BIOLOGICAL FEATURES IN-VITRO SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE ATHEROMATOSIS; SMOOTH MUSCLE PROLIFERATION; ACTIN ISOFORMS; MYOSIN; DESMIN; COLLAGEN LATTICE CONTRACTION ID ACTIN ISOFORM EXPRESSION; FACTOR-LIKE MOLECULES; GROWTH-FACTOR; CAROTID-ARTERY; MESSENGER-RNA; CYTOSKELETAL FEATURES; CULTURE CONDITIONS; PROLIFERATION; INJURY; ATHEROSCLEROSIS AB Endothelial denudation by balloon injury of the rat aorta induces the development of a neointima as a consequence of the migration and proliferation of smooth muscle cells (SMCs). Initially, intimal SMCs show a dedifferentiated phenotype, which reverts to a normal differentiated phenotype after endothelial cells have resurfaced the vessel lumen. We investigated in vitro the proliferative and phenotypic features of SMCs from different layers of rat aorta isolated 15 and 60 days after endothelial denudation. Freshly isolated intimal cells 15 days after balloon injury (IT-15) appeared rounded and showed a decreased content of alpha-smooth muscle actin, smooth muscle myosin, and desmin compared with intimal cells isolated 60 days after balloon injury (IT-60). No morphological and cytoskeletal differences were observed among freshly isolated IT-60 cells and other medial populations, which included medial SMCs that underlie the intimal thickening. In culture, IT-15 cells showed increased proliferative activity both in monolayers and in free-floating collagen lattices. Decreased expression of alpha-smooth muscle actin and smooth muscle myosin was documented in IT-15 cells compared with IT-60 cells and other medial SMC populations in monolayer. Moreover, IT-15 cells suspended in collagen lattices were poor at contracting these collagen lattices compared with IT-60 and control SMCs. IT-60 cells were equivalent to control SMCs at lattice contraction except for a temporary delay at day 1. Cells from the media underlying the intimal thickening isolated 15 and 60 days after balloon injury proliferated less, had an increased content of alpha-smooth muscle actin, and had a greater percentage of alpha-smooth muscle actin mRNA per total actin mRNA compared with IT-60 and control SMCs. Our model appears suitable to investigate the adaptation of differently derived SMC populations to various stimuli and factors involved in SMC phenotypic modulation. C1 UNIV GENEVA,DEPT PATHOL,CH-1211 GENEVA 4,SWITZERLAND. UNIV ROMA TOR VERGATA,DEPT PATHOL,ROME,ITALY. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. OI orlandi, augusto/0000-0001-7202-5854; Spagnoli, Luigi Giusto/0000-0002-0684-5501 NR 51 TC 97 Z9 98 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD JUN PY 1994 VL 14 IS 6 BP 982 EP 989 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NQ536 UT WOS:A1994NQ53600018 PM 8199190 ER PT J AU ARNASON, JA PATEL, A SUNDSTROM, WR AF ARNASON, JA PATEL, A SUNDSTROM, WR TI TRANSTHORACIC AND TRANSESOPHAGEAL ECHOCARDIOGRAPHIC EVALUATION OF THE AORTIC ROOT AND SUBVALVULAR STRUCTURES IN ANKYLOSING-SPONDYLITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1994 VL 37 IS 6 SU S BP R13 EP R13 PG 1 WC Rheumatology SC Rheumatology GA NP830 UT WOS:A1994NP83000034 ER PT J AU BORIGINI, MJ PAULUS, HE CLEMENTS, PJ PERSSELIN, JE AF BORIGINI, MJ PAULUS, HE CLEMENTS, PJ PERSSELIN, JE TI CLINICAL EFFICACY OF IMMUNOADSORPTION OF RHEUMATOID-ARTHRITIS (RA) PLASMA ON PROTEIN-A COLUMNS MAY BE RELATED TO ALTERATIONS IN PLASMA ANTI-IGG ANTIBODY-LEVELS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1994 VL 37 IS 6 SU S BP R7 EP R7 PG 1 WC Rheumatology SC Rheumatology GA NP830 UT WOS:A1994NP83000016 ER PT J AU YUNIS, JJ SALAZAR, M DEULOFEUT, R IGLESIAS, A NATES, J MEJIA, J YUNIS, E AF YUNIS, JJ SALAZAR, M DEULOFEUT, R IGLESIAS, A NATES, J MEJIA, J YUNIS, E TI DRB1-ASTERISK-0404 ALLELE AND RHEUMATOID-ARTHRITIS IN THE GUAMBIANO-AMERINDIAN TRIBE OF COLOMBIA SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOGENET,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. INST NACL SALID,BOGOTA,COLOMBIA. UNIV CAUCA,POPAYAO,COLOMBIA. UNIV NACL COLOMBIA,FAC MED,INST GENET,BOGOTA,COLOMBIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUN PY 1994 VL 37 IS 6 SU S BP R21 EP R21 PG 1 WC Rheumatology SC Rheumatology GA NP830 UT WOS:A1994NP83000074 ER PT J AU DUNKIN, JJ LEUCHTER, AF NEWTON, TF COOK, IA AF DUNKIN, JJ LEUCHTER, AF NEWTON, TF COOK, IA TI REDUCED EEG COHERENCE IN DEMENTIA - STATE OR TRAIT MARKER SO BIOLOGICAL PSYCHIATRY LA English DT Article DE EEG COHERENCE; ALZHEIMERS DISEASE; DEMENTIA; QUANTITATIVE EEG; QEEG RELIABILITY ID MULTI-INFARCT DEMENTIA; MILD SENILE DEMENTIA; ALZHEIMER-TYPE; DIFFERENTIAL-DIAGNOSIS; ELDERLY SUBJECTS; HUMAN-BRAIN; DISEASE; RELIABILITY; PATTERNS; TASK AB Recent work from our laboratory demonstrated that quantitative electroencephalographic (EEG) coherence between brain areas linked by long cortico-cortical fibers (termed ''fascicle'' coherence) was differentially reduced in subjects with Alzheimer's disease, whereas coherence between brain areas linked by short cortico-cortical and cortico-subcortical fibers in postcentral areas (termed ''visual'' coherence) was differentially reduced in subjects with multi-infarct dementia. In this study, we investigated whether these differences in coherence represent ''trait'' or ''state'' markers for dementia. Visual coherence demonstrated high stability in both demented groups as assessed by both one-year test-retest reliabilities and analysis of group mean change. Fascicle coherence demonstrated good stability in multi-infarct dementia and control subjects, but some variability was observed in Alzheimer's subjects, suggesting both state and trait factors may be involved. These findings complement neuropathologic studies, and suggest that decreases in coherence may serve as a diagnostic trait markers for these two types of dementia. The role of state factors in Alzheimer's disease requires further investigation. C1 UNIV CALIF LOS ANGELES,NEUROPSYCHIAT INST & HOSP,QUANTITAT EEG LAB,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. OI newton, thomas/0000-0002-3198-5901 FU NIA NIH HHS [P30 AG 10123]; NIMH NIH HHS [NIMH MH 40705, NIMH MH 00665] NR 25 TC 65 Z9 73 U1 0 U2 2 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 JUN 1 PY 1994 VL 35 IS 11 BP 870 EP 879 DI 10.1016/0006-3223(94)90023-X PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NN547 UT WOS:A1994NN54700007 PM 8054410 ER PT J AU HIROBE, S HE, WW GUSTAFSON, ML MACLAUGHLIN, DT DONAHOE, PK AF HIROBE, S HE, WW GUSTAFSON, ML MACLAUGHLIN, DT DONAHOE, PK TI MULLERIAN-INHIBITING SUBSTANCE GENE-EXPRESSION IN THE CYCLING RAT OVARY CORRELATES WITH RECRUITED OR GRAAFIAN FOLLICLE SELECTION SO BIOLOGY OF REPRODUCTION LA English DT Article ID RIBONUCLEIC-ACID; OOCYTE MEIOSIS; SERTOLI CELLS; ESTROUS-CYCLE; HORMONE; DIFFERENTIATION; ONTOGENY; INVITRO; BOVINE; GROWTH AB Throughout the estrous cycle, Mullerian inhibiting substance (MIS) mRNA signals, as detected by in situ hybridization, were found to be intense in granulosa cells of growing preantral and small antral follicles, especially in the layer closest to the oocyte. Neither primordial follicles, typical atretic follicles, nor CL expressed detectable signals. MIS mRNA signals seen in the cumulus cells of preovulatory follicles at 1000 and 1600 h of proestrus sharply declined at 2400 h, just before ovulation. MIS mRNA signals were intense and uniform in all newly recruited growing antral and Graafian follicles (> 350 mu m) at 1000 h of estrus but became heterogeneous in their expression of MIS on metestrus and diestrus and notably absent in atretic follicles; these findings suggest that MIS expression is correlated with recruited follicle selection and suppression with selection for atresia. The fact that all the MIS-positive growing follicles contain oocytes arrested in meiosis, coupled with previous experimental evidence that MIS inhibits germinal vesicle breakdown, suggests that MIS also might act as a regulator of oocyte maturation. C1 MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [NCI CA-17393]; NICHD NIH HHS [NICHD P30 HD 28738] NR 36 TC 48 Z9 48 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUN PY 1994 VL 50 IS 6 BP 1238 EP 1243 DI 10.1095/biolreprod50.6.1238 PG 6 WC Reproductive Biology SC Reproductive Biology GA NM630 UT WOS:A1994NM63000005 PM 8080912 ER PT J AU CHEN, ZH SWISSHELM, K SAGER, R AF CHEN, ZH SWISSHELM, K SAGER, R TI A CAUTIONARY NOTE ON REACTION TUBES FOR DIFFERENTIAL DISPLAY AND CDNA AMPLIFICATION IN THERMAL CYCLING SO BIOTECHNIQUES LA English DT Note ID MESSENGER-RNAS; CLONING RP CHEN, ZH (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC GENET,44 BINNEY ST,BOSTON,MA 02115, USA. NR 5 TC 13 Z9 18 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 JUN PY 1994 VL 16 IS 6 BP 1002 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP970 UT WOS:A1994NP97000006 PM 8074859 ER PT J AU GOTO, T MAROTA, JJA CROSBY, G AF GOTO, T MAROTA, JJA CROSBY, G TI PENTOBARBITAL, BUT NOT PROPOFOL, PRODUCES PREEMPTIVE ANALGESIA IN THE RAT FORMALIN MODEL SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE ANESTHETICS, IV, PENTOBARBITAL; ANESTHETICS, IV, PROPOFOL; RECEPTORS, AMINO ACID; ANALGESIA, PREEMPTIVE; RAT,; MODEL, RAT ID EXCITATORY AMINO-ACIDS; CENTRAL SENSITIZATION; SPINAL-CORD; HYPERALGESIA; RECEPTORS; MORPHINE; ANTAGONISM; CHANNELS; INJURY AB Injection of formalin into the hindpaw of a rat induces a biphasic response in pain-related behaviours, such that C-fibre activation during phase I triggers a state of central sensitization characterized by a longer lasting phase 2. As the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may participate in processing of nociceptive inputs, we hypothesized that pentobarbitone and propofol, iv. anaesthetics with known GABA(A) agonist properties, would interfere with development of central sensitization and thereby modify the phase 2 hyperalgesic response. Pentobarbitone administered i. v. before injection of formalin produced dose-dependent suppression of phase 2, even though animals had recovered from anaesthesia, whereas it had substantially less effect when given after phase 1 had resolved. Picrotoxin, a GABA(A) antagonist, reversed the effect of pentobarbitone on phase 2 pain behaviour but was itself a mild analgesic. in contrast, propofol had no effect on phase 2 formalin-induced pain behaviour. Thus we conclude that pentobarbitone, but not propofol, produced pre-emptive analgesia in this model, presumably by suppressing noxious stimulation-induced central sensitization via activation of GABA(A) receptors. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02114. FU NIGMS NIH HHS [NIGMS ROI GM42466] NR 24 TC 27 Z9 29 U1 0 U2 1 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD JUN PY 1994 VL 72 IS 6 BP 662 EP 667 DI 10.1093/bja/72.6.662 PG 6 WC Anesthesiology SC Anesthesiology GA NR734 UT WOS:A1994NR73400011 PM 8024913 ER PT J AU DIAMOND, D DOANE, JA AF DIAMOND, D DOANE, JA TI DISTURBED ATTACHMENT AND NEGATIVE AFFECTIVE STYLE - AN INTERGENERATIONAL SPIRAL SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID EXPRESSED EMOTION; FAMILY; DISORDERS; ILLNESS; SCHIZOPHRENIA; DEPRESSIVES; PREDICTORS; RELAPSE; BONDS AB The relationship between the quality of parents' attachment to their own parents and the quality of affective style was examined with a sample of 49 severely disturbed young adults and adolescents and their families receiving long-term in-patient treatment. Measures reflecting disturbances in attachment of parents to their own parents, derived from a five-minute speech sample task, were strongly associated with measures of negative affective style (e.g., criticism, intrusiveness and guilt induction) in face-to-face interactions with the disturbed offspring, as assessed through videotaped discussions of conflictual family issues after three months of treatment. The most significant findings involved the linkages between disturbances in the mother's attachment to her own mother and the degree of negative affect directed at the child patient. The association between disturbed intergenerational parental attachments and negative affective style supports the hypothesis that the parent's own internal burdens, stemming from disturbed attachment representations, particularly of the same-sex parent, may be a driving force behind the negative affect they display in interactions with their disturbed offspring. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP DIAMOND, D (reprint author), CORNELL UNIV,NEW YORK HOSP,COLL MED,DEPT PSYCHIAT,WESTCHESTER DIV,21 BLOOMINGDALE RD,WHITE PLAINS,NY 10605, USA. FU NIMH NIH HHS [MH44991] NR 54 TC 22 Z9 22 U1 3 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUN PY 1994 VL 164 BP 770 EP 781 DI 10.1192/bjp.164.6.770 PG 12 WC Psychiatry SC Psychiatry GA NR864 UT WOS:A1994NR86400008 PM 7952983 ER PT J AU MCCLOSKEY, M MACARUSO, P AF MCCLOSKEY, M MACARUSO, P TI ARCHITECTURE OF COGNITIVE NUMERICAL PROCESSING MECHANISMS - CONTRASTING PERSPECTIVES ON THEORY DEVELOPMENT AND EVALUATION SO CAHIERS DE PSYCHOLOGIE COGNITIVE-CURRENT PSYCHOLOGY OF COGNITION LA English DT Article DE NUMERICAL COGNITION; DYSCALCULIA ID MULTIPLE SEMANTICS; SYSTEM; DYSCALCULIA; CONFUSIONS AB This article discusses two alternative approaches to theory development and evaluation in the domain of numerical processing. Taking as an example a recent study of a brain-damaged patient with deficits in numerical processing (Macaruso, McCloskey, & Aliminosa, 1993), we contrast the approach taken by our colleagues and ourselves (e.g., McCloskey et al., 1985; McCloskey, 1992) with that adopted by Campbell and Clark (1988, 1992; Campbell, this issue; Clark & Campbell, 1991). We suggest that whereas the modular model proposed by our colleagues and ourselves represents an attempt to develop a model sufficiently constrained and explicit to generate specific testable predictions, Campbell and Clark's encoding complex approach is unconstrained and inexplicit, and does not constitute a specific theory that is subject to empirical test. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP MCCLOSKEY, M (reprint author), JOHNS HOPKINS UNIV,DEPT COGNIT SCI,BALTIMORE,MD 21218, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU ADRSC-ASSOC DIFFUSION RECHERCHES SCIENCES COGNITIVES PI MARSEILLE CEDEX 13 PA IBHOP, TRAVERSE CHARLES SUSINI, 13388 MARSEILLE CEDEX 13, FRANCE SN 0249-9185 J9 CAH PSYCHOL COGN JI Cah. Psychol. Cogn.-Curr. Psychol. Cogn. PD JUN PY 1994 VL 13 IS 3 BP 275 EP 295 PG 21 WC Psychology, Experimental SC Psychology GA NX026 UT WOS:A1994NX02600002 ER PT J AU WILLETT, CG COMPTON, CC SHELLITO, PC EFIRD, JT AF WILLETT, CG COMPTON, CC SHELLITO, PC EFIRD, JT TI SELECTION FACTORS FOR LOCAL EXCISION OR ABDOMINOPERINEAL RESECTION OF EARLY-STAGE RECTAL-CANCER SO CANCER LA English DT Article DE RECTAL CANCER; LOCAL EXCISION; ABDOMINOPERINEAL RESECTION; RADIATION THERAPY ID RADIATION-THERAPY; FAILURE AB Background. This study reviews the experience of patients with early stage rectal cancer managed by local excision or abdominoperineal resection to clarify the relative indications and results of these two approaches. Methods. From 1962 to 1991, 125 patients with T1 and T2 rectal cancer underwent local excision (56 patients) or abdominoperineal resection (69 patients). Outcome was analyzed by stage, treatment, and pathologic features of tumor grade and vessel involvement. Results. The 5-year actuarial recurrence-free survival and local control was 87% and 96%, respectively, for 28 patients undergoing local excision with favorable histologic features (well or moderately well differentiated histologic findings without venous/lymph vessel involvement). These results were 57% and 68% for 28 patients with unfavorable histologic features (poorly differentiated histology and/or venous/lymph vessel involvement). For patients undergoing abdominoperineal resection, the 5-year actuarial recurrence-free survival and local control of 49 patients with favorable histologic features was 91% and 91%, respectively. These results were 79% and 89%, respectively, for patients with poorly differentiated histology or venous/lymph vessel involvement. Conclusions. For patients with T1 and T2 tumors having favorable histologic features, a satisfactory survival and local control was achieved for patients undergoing local excision or abdominoperineal resection. In contrast, patients with T1 and T2 tumors having poorly differentiated histologic features and/or venous/lymph vessel involvement undergoing local excision or abdominoperineal resection appeared to have decreased rates of survival and of local control. For these patients, radical resection combined with pelvic irradiation and 5-fluorouracil-based chemotherapy should be investigated. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DEPT SURG,BOSTON,MA 02114. RP WILLETT, CG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR CANC,DEPT RADIAT ONCOL,COX BLDG,3RD FLOOR,BOSTON,MA 02114, USA. NR 12 TC 111 Z9 114 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1994 VL 73 IS 11 BP 2716 EP 2720 DI 10.1002/1097-0142(19940601)73:11<2716::AID-CNCR2820731111>3.0.CO;2-9 PG 5 WC Oncology SC Oncology GA NP079 UT WOS:A1994NP07900010 PM 8194011 ER PT J AU STERN, RS LAIRD, N AF STERN, RS LAIRD, N TI THE CARCINOGENIC RISK OF TREATMENTS FOR SEVERE PSORIASIS SO CANCER LA English DT Article DE PSORIASIS; METHOTREXATE; PSORALEN AND ULTRAVIOLET A THERAPY; SQUAMOUS CELL CARCINOMA; BASAL CELL CARCINOMA; ULTRAVIOLET B PHOTOTHERAPY; TOPICAL TAR ID ORAL METHOXSALEN PHOTOCHEMOTHERAPY; SQUAMOUS-CELL CARCINOMA; PUVA; METHOTREXATE; RADIATION; TUMORS; CANCER AB Background. Common treatments used for severe psoriasis include psoralen and ultraviolet A radiation (PUVA), methotrexate, ultraviolet B (UVB), and tar. These therapies are often used for prolonged periods and may be carcinogenic. Methods. For more than 13 years, the authors have prospectively determined the incidence of skin cancer and use of treatments for psoriasis in a 1380 patient cohort originally enrolled in a therapeutic trial of PUVA at 16 university centers. Results. Squamous cell carcinoma (SCC) developed in more than one fourth of patients exposed to high doses of PUVA. In this group, the standard morbidity ratio for these tumors was 83 (95% confidence interval [CI], 72-96) compared with the expected number of these tumors in the general population. High-level exposure to methotrexate is a significant independent risk factor for developing SCC (relative risk, 2.1 for high versus low or no exposure; 95% CI, 1.4-2.8). Metastatic disease developed in seven patients with SCC. No significant increase in the risk of SCC was associated with long term exposure to UVB or topical tar, and no substantial increase in the risk of basal cell carcinoma was noted in association with prolonged use of any of these treatments. Conclusions. Long term exposure to PUVA and methotrexate significantly increases the risk of SCC in patients with psoriasis. This risk should be considered in selection of treatment. The ultimate morbidity of these tumors is undetermined. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP STERN, RS (reprint author), BETH ISRAEL HOSP,DEPT DERMATOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAMS NIH HHS [1-AR-3-2252] NR 20 TC 281 Z9 286 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 1994 VL 73 IS 11 BP 2759 EP 2764 DI 10.1002/1097-0142(19940601)73:11<2759::AID-CNCR2820731118>3.0.CO;2-C PG 6 WC Oncology SC Oncology GA NP079 UT WOS:A1994NP07900017 PM 8194017 ER PT J AU TEICHER, BA AF TEICHER, BA TI HYPOXIA AND DRUG-RESISTANCE SO CANCER AND METASTASIS REVIEWS LA English DT Review DE HYPOXIA; DRUG RESISTANCE; HYPOXIC CELL SELECTIVE AGENTS; RADIATION SENSITIZERS; TUMOR OXYGENATION; PHYSIOLOGICAL DRUG RESISTANCE ID FLUOSOL-DA 20-PERCENT; CHINESE-HAMSTER OVARY; FSAIIC MURINE FIBROSARCOMA; SQUAMOUS-CELL CARCINOMA; MELPHALAN ANTITUMOR-ACTIVITY; TUMOR SUBPOPULATIONS INVIVO; ALKYLATING AGENT ACTIVITY; INDUCED DNA DAMAGE; MITOMYCIN-C; CYTO-TOXICITY AB Biologically and therapeutically important hypoxia occurs in many solid tumor masses. Hypoxia can be a direct cause of therapeutic resistance because some drugs and radiation require oxygen to be maximally cytotoxic. Cellular metabolism is altered under hypoxic conditions. Hypoxia can result in drug resistance indirectly if under this condition cells more effectively detoxify the drug molecules. Finally, there is evidence that hypoxia can enhance genetic instability in tumor cells thus allowing more rapid development of drug resistance cells. The current review describes the effects of hypoxia on tumor response to a variety of anticancer agents and also describes progress toward therapeutically useful methods of delivering oxygen to tumors in an effort to overcome therapeutic resistance due to hypoxia. Finally, the use of hypoxic cell selective cytotoxic agents as a means of addressing hypoxic 'drug resistance' is discussed. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP TEICHER, BA (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. FU PHS HHS [P01-19589, P01-38493, R01-50174] NR 240 TC 346 Z9 352 U1 3 U2 30 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 1994 VL 13 IS 2 BP 139 EP 168 DI 10.1007/BF00689633 PG 30 WC Oncology SC Oncology GA NV419 UT WOS:A1994NV41900002 PM 7923547 ER PT J AU TEICHER, BA SCHWARTZ, JL HOLDEN, SA ARA, G NORTHEY, D AF TEICHER, BA SCHWARTZ, JL HOLDEN, SA ARA, G NORTHEY, D TI IN-VIVO MODULATION OF SEVERAL ANTICANCER AGENTS BY BETA-CAROTENE SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE MINOCYCLINE; BETA-CAROTENE; CYTOTOXIC ANTICANCER AGENTS ID SQUAMOUS-CELL CARCINOMA; TUMOR NECROSIS FACTOR; RETINOIC-ACID; EXPERIMENTAL CANCER; ALPHA-TOCOPHEROL; ORAL-CANCER; FRACTIONATED-IRRADIATION; ANGIOGENESIS INHIBITION; EXTRACELLULAR-MATRIX; COLLAGENASE ACTIVITY AB The ability of the collagenase inhibitor minocycline and of beta-carotene to act as positive modulators of cytotoxic anticancer agents was assessed in vitro and in vivo. Cell-culture studies were conducted using the human SCC-25 squamous carcinoma cell line. Simultaneous exposure of the cells to minocycline and beta-carotene or 13-cis-retinoic acid along with cisplatin (CDDP) resulted in a small decrease in the cytotoxicity of the CDDP. The addition of each of the modulator combinations for 1 h or 24 h to treatment with melphalan (L-PAM) or carmustine (BCNU) resulted in greater-than-additive cytotoxicity with each of four regimens. The modulator combinations of minocycline and beta-carotene applied for 1 h or 24 h and the modulator combination of minocycline and 13-cis-retinoic acid produced greater-than-additive cytotoxicity at 50 mu M 4-hydroperoxycyclophosphamide (4-HC), whereas minocycline and 13-cis-retinoic acid applied for 1 h was antagonistic with 4-HC and the other modulator treatments at low concentrations of 4-HC resulted in subadditive cytotoxicity. The effect of treatment with beta-carotene alone and in combination with several different anticancer agents was examined in two murine solid tumors, the FSaII fibrosarcoma and the SCC VII carcinoma. Administration of the modulators alone or in combination did not alter the growth of either tumor. Whereas increases in tumor growth delay occurred with the antitumor alkylating agents and beta-carotene and with minocycline and beta-carotene, a diminution in tumor growth delay was produced by 5-fluorouracil in the presence of these modulators. The modulator combination also resulted in increased tumor growth delay with Adriamycin and etoposide. Tumor-cell, survival assay showed increased killing of FSaII tumor cells with the modulator combination and melphalan or cyclophosphamide as compared with the drugs alone. These results indicate that further investigation of this modulator strategy is warranted. C1 JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,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 [R01-CA50174] NR 76 TC 26 Z9 27 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1994 VL 34 IS 3 BP 235 EP 241 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA NR195 UT WOS:A1994NR19500009 PM 8004757 ER PT J AU COOLEY, ME DAVIS, LE DESTEFANO, M ABRAHM, J AF COOLEY, ME DAVIS, LE DESTEFANO, M ABRAHM, J TI CISPLATIN - A CLINICAL REVIEW .1. CURRENT USES OF CISPLATIN AND ADMINISTRATION GUIDELINES SO CANCER NURSING LA English DT Review DE CISPLATIN; USES; ADMINISTRATION ID CELL LUNG-CANCER; HIGH-DOSE CISPLATIN; REFRACTORY OVARIAN-CARCINOMA; RANDOMIZED TRIAL; CIS-PLATINUM; INTRAPERITONEAL CHEMOTHERAPY; ONCOLOGY-GROUP; SALVAGE THERAPY; BRAIN-TUMORS; PHASE-I AB Cisplatin is one of the most active cancer treatment agents available. Unfortunately, however, cisplatin causes many untoward side effects. Nurses play a major role in administering cisplatin and in preventing and managing the adverse effects associated with this drug. In order to maximize the quality of life of patients undergoing cisplatin treatment, nurses need a thorough knowledge of its uses, administration, and side effects. This article is the first of a two-part series about cisplatin. Part I will provide a review of the mechanism of action, current uses, and administration guidelines. Part II will discuss the most common side effects of cisplatin and the appropriate nursing assessment and management of patients undergoing treatment with this agent. In addition, future directions for the use of cisplatin and the use of alternative agents will be discussed. C1 PHILADELPHIA VET AFFAIRS MED CTR,LUNG TUMOR CLIN,PHILADELPHIA,PA. DELAWARE CTY MEM HOSP,DREXEL HILL,PA. PHILADELPHIA VET AFFAIRS MED CTR,HEMATOL ONCOL SECT,PHILADELPHIA,PA. PHILADELPHIA COLL PHARM & SCI,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NR 78 TC 10 Z9 10 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD JUN PY 1994 VL 17 IS 3 BP 173 EP 184 PG 12 WC Oncology; Nursing SC Oncology; Nursing GA NP075 UT WOS:A1994NP07500001 PM 8055487 ER PT J AU PROUGH, RA WEBB, SJ WU, HQ LAPENSON, DP WAXMAN, DJ AF PROUGH, RA WEBB, SJ WU, HQ LAPENSON, DP WAXMAN, DJ TI INDUCTION OF MICROSOMAL AND PEROXISOMAL ENZYMES BY DEHYDROEPIANDROSTERONE AND ITS REDUCED METABOLITE IN RATS SO CANCER RESEARCH LA English DT Article ID ACYL-COA OXIDASE; HORMONE RECEPTOR SUPERFAMILY; GLUTATHIONE S-TRANSFERASES; TISSUE-SPECIFIC REGULATION; ACID OMEGA-HYDROXYLASES; ACTIVATED RECEPTOR; MESSENGER-RNA; BETA-OXIDATION; CLOFIBRIC ACID; FATTY-ACIDS AB Dehydroepiandrosterone (DHEA) given to rodents in pharmacological doses induces several hepatic enzymes including cytochromes P4504A, NADPH:P450 oxidoreductase, palmitoyl coenzyme A oxidase, and other enzymes associated with the peroxisomal beta-oxidation pathway, leading to peroxisome proliferation and development of hepatocellular carcinoma in rodents. Comparison of the inductive potency of DHEA and other intermediates of the steroid biosynthetic path demonstrated that only DHEA, 5-ene-androstene-3 beta,17 beta-diol (ADIOL), and to a lesser extent, 17 alpha-hydroxypregnenolone, a precursor of DHEA, induce cytochromes P4504A protein and other enzymes associated with the peroxisome proliferative response in vivo. ADIOL exerted its inductive response at a somewhat lower dosage than DHEA, whereas ADIOL and DHEA both induced the microsomal enzymes (P4504A and its oxidoreductase) at somewhat lower dosages than those required to induce peroxisomal enzymes. Northern analysis demonstrated increases in the mRNAs encoding the cytochromes P4504A (>20-fold) and NADPH:P450 oxidoreductase (>10-fold) in the livers of DHEA- and ADIOL-treated rats. Run-on transcription analysis demonstrated that DHEA induces CYP4A gene expression 11-fold at the level of transcription initiation. Comparison of the responsiveness of individual rat CYP4A genes (4A1, 4A2, and 4A3) to DHEA and ADIOL in immature versus mature male rats revealed 23-fold higher levels of induced CYP4A1 and 4A3 mRNAs in immature rat livers. In contrast, hepatic CYP4A2 mRNA was induced to 6-10-fold higher levels in mature rats. No basal or significant inducible expression of mRNA for CYP4A1 and 4A3 was noted in rat kidney. Significant basal levels of kidney CYP4A2 mRNA mere observed only in mature animals, where they were inducible by ADIOL and DHEA to a 3-5 fold greater extent than in the kidneys of immature rats. These studies demonstrate developmental differences in the responsiveness of CYP4A mRNA levels to DHEA and ADIOL in rat kidney and liver. Moreover, the striking inducibility of CYP4A protein and mRNAs, together with the increased rates of synthesis of nascent CYP4A mRNA transcripts in hepatic nuclei from DHEA-treated rats, establish that DHEA increases the expression of these microsomal enzymes at the transcriptional level. C1 UNIV LOUISVILLE,SCH MED,DEPT BIOCHEM,LOUISVILLE,KY 40292. TONGJI MED UNIV,DEPT ENVIRONM TOXICOL,WUHAN,PEOPLES R CHINA. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA43839]; NIDDK NIH HHS [DK33765]; NIEHS NIH HHS [ES04244] NR 60 TC 56 Z9 57 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1994 VL 54 IS 11 BP 2878 EP 2886 PG 9 WC Oncology SC Oncology GA NN724 UT WOS:A1994NN72400016 PM 8187072 ER PT J AU VOLK, MJ PUGH, TD KIM, M FRITH, CH DAYNES, RA ERSHLER, WB WEINDRUCH, R AF VOLK, MJ PUGH, TD KIM, M FRITH, CH DAYNES, RA ERSHLER, WB WEINDRUCH, R TI DIETARY RESTRICTION FROM MIDDLE-AGE ATTENUATES AGE-ASSOCIATED LYMPHOMA DEVELOPMENT AND INTERLEUKIN-6 DYSREGULATION IN C57BL/6 MICE SO CANCER RESEARCH LA English DT Article ID B-CELLS; HODGKINS-DISEASE; TRANSGENIC MICE; SURVIVAL; INCREASE; DIFFERENTIATION; CLASSIFICATION; TUMORIGENICITY; EXPRESSION; NEOPLASMS AB Dietary restriction (DR) started in middle age profoundly reduces the occurrence of lymphoma in C57BL/6 mice. Here, we report immunocellular and molecular changes associated with this mode of cancer prevention. Twelve-month-old male C57BL/6 mice were either fed a control diet or subjected to moderate DR (similar to 25% < control intake). DR significantly reduced lymphoma development (incidence at 25 months, 19% of 72 control mice versus 5% of 60 DR mice). Flow cytometry of splenocytes showed that DR increased the percentage of CD4(+) and CD8(+) cells. Lymphomatous spleens displayed varied labeling patterns and high percentages of cells in S phase. Splenocyte c-myc expression tended to increase with age in controls and was reduced by DR Lymphopenia and markedly reduced nucleated cell yields from peripheral lymphoid tissues were induced by DR. Serum interleukin 6 levels increased with age and were quite high (>2500 pg/ml) in several mice with lymphoma and other histopathological findings. DR attenuated this age-associated increase. Immunohistochemical studies of lymphomatous spleens showed the presence of interleukin 6 in monocytic appearing cells but not in lymphoma cells. These observations support the possibility that an age-associated interleukin 6 dysregulation is important in lymphomagenesis. C1 UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53706. UNIV WISCONSIN,DEPT NUTR SCI,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI 53705. TOXICOL PATHOL ASSOCIATES,LITTLE ROCK,AR 72211. UNIV UTAH,SCH MED,DEPT PATHOL,SALT LAKE CITY,UT 84132. NR 42 TC 51 Z9 52 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 JUN 1 PY 1994 VL 54 IS 11 BP 3054 EP 3061 PG 8 WC Oncology SC Oncology GA NN724 UT WOS:A1994NN72400044 PM 8187095 ER PT J AU CHRISTIANI, DC YE, TT WEGMAN, DH EISEN, EA DAI, HL LU, PL AF CHRISTIANI, DC YE, TT WEGMAN, DH EISEN, EA DAI, HL LU, PL TI PULMONARY-FUNCTION AMONG COTTON TEXTILE WORKERS - A STUDY OF VARIABILITY IN SYMPTOM REPORTING, ACROSS-SHIFT DROP IN FEV(1), AND LONGITUDINAL CHANGE SO CHEST LA English DT Article ID CHRONIC LUNG-DISEASE; GRAIN ELEVATOR WORKERS; REPUBLIC-OF-CHINA; RESPIRATORY-DISEASE; DUST EXPOSURE; OPERATIVES; DECLINE; MILLS; FEV1 AB Longitudinal variability in respiratory responses, including symptom reporting and across-shift change in ventilatory function, were examined in relation to long-term loss of ventilatory function in a group of 447 cotton textile workers in Shanghai, China. The study used a standardized respiratory questionnaire and standardized spirometric testing before and after a work shift on the first day of the workweek. Prediction equations for FEV(1) were generated from a group of silk textile workers from the same city. Environmental samples included both vertical elutriated cotton dust and endotoxin levels. There was considerable variability in symptom reporting between the baseline and g-year follow-up survey for all symptoms. However, subjects who consistently reported symptoms had a significantly accelerated 5-year loss in FEV(1) compared with those who never reported symptoms. Subjects with symptoms of chest tightness or dyspnea at one survey lost FEV(1) at a rate intermediate between the never or both groups. Moreover, subjects with an cross-shift change in FEV(1) of more than 5 percent at both surveys had the greatest loss in FEV(1) over 5 years (-267 ml) when compared with one-time responders (-224 ml), and nonresponders (-180 ml), though the differences were not significant. Workers with chest tightness and chronic bronchitis in both surveys were overrepresented in the high dust and endotoxin areas. Our results indicate that even with substantial survey-to-survey variability in responses, there is important information contained in both questionnaires and across-shift spirometry. Among cotton workers, consistent responders to either symptom questionnaire or across-shift FEV(1) decrements of greater than or equal to 5 percent appear to be at increased risk for lung function impairment. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA. MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. UNIV MASSACHUSETTS,DEPT WORK ENVIRONM,LOWELL,MA. SHANGHAI MED UNIV,SCH PUBL HLTH,INST PREVENT MED,SHANGHAI 200032,PEOPLES R CHINA. SHANGHAI TEXT BUR,FIRST HOSP,SHANGHAI,PEOPLES R CHINA. FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [R01OHO2421] NR 32 TC 27 Z9 27 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUN PY 1994 VL 105 IS 6 BP 1713 EP 1721 DI 10.1378/chest.105.6.1713 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NT064 UT WOS:A1994NT06400022 PM 8205865 ER PT J AU HUSAIN, M ADRIE, C ICHINOSE, F KAVOSI, M ZAPOL, WM AF HUSAIN, M ADRIE, C ICHINOSE, F KAVOSI, M ZAPOL, WM TI EXHALED NITRIC-OXIDE AS A MARKER FOR ORGANIC NITRATE TOLERANCE SO CIRCULATION LA English DT Note DE NITROGLYCERIN; SODIUM NITROPRUSSIDE ID CONGESTIVE-HEART-FAILURE; INTRAVENOUS NITROGLYCERIN; ACTIVATION; AIR AB Background This study was designed to demonstrate the development of biochemical tolerance to organic nitrates by measuring levels of exhaled gaseous nitric oxide (NO) in lambs given intravenous (IV) nitroglycerin or sodium nitroprusside. Methods and Results IV injections of nitroglycerin or sodium nitroprusside produced dose-dependent and sustained increases in the exhaled levels of nitric oxide measured by chemiluminescence in awake lambs with tracheostomies. After a 6-hour IV infusion of 25 mu g.kg(-1) min(-1) nitroglycerin, peak exhaled NO levels were significantly reduced (-53.6+/-4.9%, mean+/-SEM, P<.001) and systemic hypotensive responses were attenuated (-52.6+/-5.9%, P<.001) after an IV challenge of nitroglycerin but not sodium nitroprusside. After a subsequent 12-hour nitroglycerin-free period, there was complete recovery of NO excretion in exhaled breath and a return to baseline of systemic hypotensive changes on administration of TV nitroglycerin boluses. For IV sodium nitroprusside challenges, pulmonary NO excretion and systemic hypotensive responses remained constant throughout the study. Challenges with IV nitroglycerin but not sodium nitroprusside during a 12-hour nitroglycerin-free period resulted in delayed biochemical recovery with various exhaled NO levels and systemic hypotensive responses to challenges with IV nitroglycerin. Conclusions Measurements of exhaled NO provide in vivo, noninvasive evidence for the development of biochemical tolerance to nitroglycerin. There was reduced NO release into exhaled gas from the pulmonary vasculature concomitant with evidence of tolerance to nitroglycerin vasodilation in the systemic circulation. C1 MASSACHUSETTS GEN HOSP,HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. FU NHLBI NIH HHS [HL-42397] NR 12 TC 47 Z9 47 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 JUN PY 1994 VL 89 IS 6 BP 2498 EP 2502 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NQ830 UT WOS:A1994NQ83000006 PM 8205655 ER PT J AU DISALVO, TG TATTER, SB OGARA, PT NIELSEN, GP DESANCTIS, RW AF DISALVO, TG TATTER, SB OGARA, PT NIELSEN, GP DESANCTIS, RW TI FATAL INTRACEREBRAL HEMORRHAGE FOLLOWING THROMBOLYTIC THERAPY OF EMBOLIC MYOCARDIAL-INFARCTION IN UNSUSPECTED INFECTIVE ENDOCARDITIS SO CLINICAL CARDIOLOGY LA English DT Note DE THROMBOLYTIC THERAPY; INTRACEREBRAL HEMORRHAGE; EMBOLIC MYOCARDIAL INFARCTION; INFECTIVE ENDOCARDITIS ID BACTERIAL-ENDOCARDITIS; ECHOCARDIOGRAPHY AB Cerebral hemorrhage occurs in 0.2% of patients under the age of 60 years treated with thrombolytic therapy for acute myocardial infarction. A case of fatal cerebral hemorrhage following TPA therapy for myocardial infarction due to probable coronary artery embolism during unsuspected native valve infective endocarditis is reported. RP DISALVO, TG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,ACC475,WANG BLDG,FRUIT ST,BOSTON,MA 02114, USA. NR 24 TC 18 Z9 19 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD JUN PY 1994 VL 17 IS 6 BP 340 EP 344 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NN480 UT WOS:A1994NN48000011 PM 8070153 ER PT J AU JACOBY, GA AF JACOBY, GA TI PREVALENCE AND RESISTANCE MECHANISMS OF COMMON BACTERIAL RESPIRATORY PATHOGENS SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID PENICILLIN-BINDING PROTEINS; CATARRHALIS BETA-LACTAMASE; INFLUENZAE TYPE-B; STREPTOCOCCUS-PNEUMONIAE; BRANHAMELLA-CATARRHALIS; HAEMOPHILUS-INFLUENZAE; ANTIMICROBIAL RESISTANCE; HEMOPHILUS-INFLUENZAE; UNITED-STATES; ANTIBIOTIC-RESISTANCE AB Organisms causing common infections of the respiratory tract are becoming increasingly resistant to antimicrobial agents. In 1990-1991 between 15% and 20% of isolates of Streptococcus pneumoniae from the United States had MICs of penicillin G of greater than or equal to 0.1 mu g/mL and 2%-3% had R MICs of greater than or equal to 1.0 mu g/mL. The percentage of isolates that are resistant is even higher in other parts of the world. Although most penicillin-resistant strains of S. pneumoniae are susceptible to broad-spectrum cephalosporins, a few isolates resistant to cefuroxime, cefotaxime, and ceftriaxone have appeared. Unlike other respiratory pathogens in which the production of beta-lactamase is responsible for resistance, S. pneumoniae exhibits resistance that is caused by alterations in penicillin-binding proteins. Consequently, beta-lactam/beta-lactamase inhibitor combinations have no particular value against resistant pneumococci. Furthermore, penicillin-resistant pneumococci are often coresistant to macrolides, sulfa-based drugs, and tetracycline. Knowledge of how resistance is attained presumably will further the development of new strategies for treatment. The mechanisms of resistance of pneumococci and other common respiratory pathogens (particularly Haemophilus influenzae and Moraxella catarrhalis) to standard antimicrobial agents are examined in this report. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. NR 73 TC 56 Z9 57 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 JUN PY 1994 VL 18 IS 6 BP 951 EP 957 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NQ826 UT WOS:A1994NQ82600018 PM 8086559 ER PT J AU CIVEN, R BERLIN, G PANOSIAN, C AF CIVEN, R BERLIN, G PANOSIAN, C TI VERTEBRAL OSTEOMYELITIS AFTER INTRAVESICAL ADMINISTRATION OF BACILLE CALMETTE-GUERIN SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID BLADDER-CANCER; THERAPY; COMPLICATIONS; IMMUNOTHERAPY; INFECTION C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV INFECT DIS,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,SCH MED,DIV INFECT DIS,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,MED CTR,DEPT PATHOL & LAB MED,CLIN MICROBIOL SECT,LOS ANGELES,CA 90024. NR 10 TC 16 Z9 16 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 JUN PY 1994 VL 18 IS 6 BP 1013 EP 1014 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NQ826 UT WOS:A1994NQ82600035 PM 8086533 ER PT J AU FLYNN, JM SPRINGFIELD, DS MANKIN, HJ AF FLYNN, JM SPRINGFIELD, DS MANKIN, HJ TI OSTEOARTICULAR ALLOGRAFTS TO TREAT DISTAL FEMORAL OSTEONECROSIS SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID KNEE; CARTILAGE AB Allografts, which are among the limited number of treatment options for young patients with large defects of the distal femur, offer a physiologic method of restoring knee function. Since 1980, 21 patients younger than 50 years old who had osteonecrosis involving large portions of the distal femur were treated with fresh-frozen osteoarticular surface replacements. This retrospective review evaluated the 15 patients (17 knees) whose followup time was greater than two years. The patients were reevaluated at regular intervals by one or more of the authors. Follow-up time ranged from two to nine Sears (mean, 4.2 years). Outcome was classified as either excellent, good (occasional complaints, unlimited walking without aids, functional range of motion), fair (intermittent pain, ambulatory tolerance limited), or failure. There were seven excellent results, five good results, one fair result, and four failures. There were no infections, nonunions, or wound complications. At this early follow-up period, 12 (70%) of the 17 knees have been successfully treated. The authors' success rate with frozen allografts is comparable to the results of fresh allograft resurfacing. Use of frozen allografts allows time for thorough testing for viral and bacterial infections, is more practical, and the allografts are available for use in elective surgery. Failure in this series was principally the result of degeneration of the allograft's articular cartilage, or fracture of the allograft. C1 MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,BOSTON,MA 02114. NR 19 TC 54 Z9 54 U1 0 U2 1 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 JUN PY 1994 IS 303 BP 38 EP 43 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA NP391 UT WOS:A1994NP39100006 PM 8194252 ER PT J AU KAPLAN, JC HIRSCH, MS AF KAPLAN, JC HIRSCH, MS TI THERAPY OTHER THAN REVERSE-TRANSCRIPTASE INHIBITORS FOR HIV-INFECTION SO CLINICS IN LABORATORY MEDICINE LA English DT Review RP KAPLAN, JC (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,149 13TH ST,BOSTON,MA 02129, 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 1994 VL 14 IS 2 BP 367 EP 391 PG 25 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PD131 UT WOS:A1994PD13100011 PM 7523020 ER PT J AU DAQUILA, RT AF DAQUILA, RT TI HIV-1 DRUG-RESISTANCE - MOLECULAR PATHOGENESIS AND LABORATORY MONITORING SO CLINICS IN LABORATORY MEDICINE LA English DT Review RP DAQUILA, RT (reprint author), MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,149 13TH ST,BOSTON,MA 02129, USA. NR 0 TC 23 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD JUN PY 1994 VL 14 IS 2 BP 393 EP 422 PG 30 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PD131 UT WOS:A1994PD13100012 PM 7523021 ER PT J AU GUY, SM SMITH, GM BENTLER, PM AF GUY, SM SMITH, GM BENTLER, PM TI THE INFLUENCE OF ADOLESCENT SUBSTANCE USE AND SOCIALIZATION ON DEVIANT-BEHAVIOR IN YOUNG ADULTHOOD SO CRIMINAL JUSTICE AND BEHAVIOR LA English DT Article ID DRUG-USE; SENSATION SEEKING; SEX-DIFFERENCES; ALCOHOL-USE; DELINQUENCY; CONSEQUENCES; PERSONALITY; ANTECEDENTS; IMPACT; MODEL AB This study examined the impact of adolescent substance use on adult substance use and criminal behavior. Longitudinal data from 657 participants were assessed over 12 years (1969-1981). Latent variable models were used to determine what effect, if any, adolescent drug use had on later deviance. In addition, constructs relevant to traditional theories of social control, such as the extent of socialization and obedience to rules, were also included as predictors. The results showed that a general drug use factor in adolescence significantly predicted adult illicit substance use, theft, and interpersonal aggression. Drug-related accidents (automobile and other) were also predicted from adolescent drug use. These findings are consistent with several theories suggesting that different forms of deviance may influence each other over time. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP GUY, SM (reprint author), UNIV CALIF LOS ANGELES,DEPT PSYCHOL,LOS ANGELES,CA 90024, USA. NR 46 TC 11 Z9 11 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0093-8548 J9 CRIM JUSTICE BEHAV JI Crim. Justice Behav. PD JUN PY 1994 VL 21 IS 2 BP 236 EP 255 DI 10.1177/0093854894021002004 PG 20 WC Psychology, Clinical; Criminology & Penology SC Psychology; Criminology & Penology GA NL803 UT WOS:A1994NL80300004 ER PT J AU NISHIMURA, M IMANAKA, H YOSHIYA, I KACMAREK, RM AF NISHIMURA, M IMANAKA, H YOSHIYA, I KACMAREK, RM TI COMPARISON OF INSPIRATORY WORK OF BREATHING BETWEEN FLOW-TRIGGERED AND PRESSURE-TRIGGERED DEMAND FLOW SYSTEMS IN RABBITS SO CRITICAL CARE MEDICINE LA English DT Article DE VENTILATOR; PRESSURE SUPPORT VENTILATION; NEONATE; WORK OF BREATHING; INTUBATION, ENDOTRACHEAL; MECHANICAL VENTILATION; PULMONARY EMERGENCIES; CRITICAL ILLNESS; PEDIATRICS ID POSITIVE AIRWAY PRESSURE; MECHANICAL VENTILATION; PLEURAL PRESSURE; SUPPORT; EFFICACY AB Objectives: Flow-triggered continuous positive airway pressure decreases the inspiratory work of breathing in adults when compared with pressure-triggered continuous positive airway pressure. However, the effect of flow-triggered continuous positive airway pressure on work of breathing in neonates is not known. Our objective was to determine if flow triggering was superior to pressure triggering in the presence of narrow endotracheal tubes, such as those tubes used in neonates. Design: Prospective evaluation using within-animal comparison of flow-triggering and pressure-triggering demand flow systems. Setting: The animal laboratory in a university hospital. Subjects: Six spontaneously breathing white rabbits, tracheostomized and intubated with 3- and 4-mm inner diameter endotracheal tubes. Interventions: The animals were connected to a ventilator through a standard respiratory circuit. The ventilator was randomly operated in the following modes: flow-triggered continuous positive ah-way pressure, pressure-triggered continuous positive airway pressure, flow-triggered with 5 cm H2O pressure support ventilation, and pressure-triggered with 5 cm H2O pressure support ventilation. Measurements and Main Results: Esophageal pressure, airway pressure, and flow signals were monitored. Control data were obtained while the rabbits were breathing room air through the endotracheal tube. With 3-mm inner diameter endotracheal tubes, the negative deflection of esophageal pressure during flow-triggered continuous positive airway pressure was significantly less than control; however, negative deflection of esophageal pressure during pressure-triggered continuous positive airway pressure did not significantly differ from control The application of 5 cm H2O pressure support ventilation with flow-triggering decreased negative deflection of esophageal pressure significantly compared with flow-triggered continuous positive airway pressure, pressure-triggered continuous positive airway pressure, and control. With endotracheal tube inner diameter of 4 mm, flow-triggered continuous positive airway pressure and pressure-triggered continuous positive airway pressure did not show any differences compared to control. Negative deflection of esophageal pressure differed under ah conditions except control when results with the 3-mm inner diameter endotracheal tube were compared with the 4-mm inner diameter endotracheal tube. Conclusions: Flow-triggering is superior to pressure-triggering in the presence of a 3-mm inner diameter endotracheal tube. This difference was not clear with a 4-mm inner diameter endotracheal tube. The size of the endotracheal tube may be the most important variable in evaluating the approach used to ventilate small neonates. C1 OSAKA UNIV,SCH MED,DEPT ANESTHESIOL,OSAKA 553,JAPAN. OSAKA UNIV HOSP,INTENS CARE UNIT,OSAKA 553,JAPAN. RP NISHIMURA, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT RESP,RESP CARE SERV,ELLISON 4,FRUIT ST,BOSTON,MA 02114, USA. NR 25 TC 14 Z9 14 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 JUN PY 1994 VL 22 IS 6 BP 1002 EP 1009 DI 10.1097/00003246-199406000-00020 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA PL759 UT WOS:A1994PL75900019 PM 8205807 ER PT J AU DIAMOND, MS SPRINGER, TA AF DIAMOND, MS SPRINGER, TA TI THE DYNAMIC REGULATION OF INTEGRIN ADHESIVENESS SO CURRENT BIOLOGY LA English DT Review ID FUNCTION-ASSOCIATED ANTIGEN-1; GLYCOPROTEIN-IIB-IIIA; INTERCELLULAR-ADHESION MOLECULE-1; MEDIATES NEUTROPHIL ADHESION; PERIPHERAL-BLOOD LYMPHOCYTES; INCREASED SURFACE EXPRESSION; T-CELL ADHESION; LEUKOCYTE ADHESION; CYTOPLASMIC DOMAIN; MONOCLONAL-ANTIBODY C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,COMM CELL & DEV BIOL,BOSTON,MA 02115. NR 118 TC 400 Z9 405 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 1 PY 1994 VL 4 IS 6 BP 506 EP 517 DI 10.1016/S0960-9822(00)00111-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NU410 UT WOS:A1994NU41000004 PM 7922371 ER PT J AU COLLINS, TL KASSNER, PD BIERER, BE BURAKOFF, SJ AF COLLINS, TL KASSNER, PD BIERER, BE BURAKOFF, SJ TI ADHESION RECEPTORS IN LYMPHOCYTE-ACTIVATION SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID T-CELL ACTIVATION; STIMULATES TYROSINE PHOSPHORYLATION; HUMAN B-CELLS; SIGNAL-TRANSDUCTION; EXTRACELLULAR-MATRIX; CYTOPLASMIC DOMAIN; VITRONECTIN RECEPTOR; DEPENDENT ACTIVATION; MONOCLONAL-ANTIBODY; INTEGRIN ACTIVATION AB The past several years have seen significant progress in understanding the role of T lymphocyte coreceptors in adhesion and activation. New insights have been gained in several areas: the avidity regulation of beta 1 and beta 2 integrins and their role in signal transduction; the regulation of CD8 avidity; the role of Lck in CD4 coreceptor activity; and the novel role for CD2 adhesion in the T cell antigen response. C1 HARVARD UNIV,SCH MED,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DANA FARBER CANC INST,BOSTON,MA. FU NCI NIH HHS [CA42367]; NIAID NIH HHS [AI31868, AI17258] NR 94 TC 94 Z9 94 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD JUN PY 1994 VL 6 IS 3 BP 385 EP 393 DI 10.1016/0952-7915(94)90117-1 PG 9 WC Immunology SC Immunology GA NT815 UT WOS:A1994NT81500006 PM 7917106 ER PT J AU GREENFIELD, S KAPLAN, SH SILLIMAN, RA SULLIVAN, L MANNING, W DAGOSTINO, R SINGER, DE NATHAN, DM AF GREENFIELD, S KAPLAN, SH SILLIMAN, RA SULLIVAN, L MANNING, W DAGOSTINO, R SINGER, DE NATHAN, DM TI THE USES OF OUTCOMES RESEARCH FOR MEDICAL EFFECTIVENESS, QUALITY OF CARE, AND REIMBURSEMENT IN TYPE-II DIABETES SO DIABETES CARE LA English DT Article; Proceedings Paper CT Symposium on Diabetes Translation: A Blueprint for the Future CY SEP 24-25, 1992 CL INT DIABETES CTR, MINNEAPOLIS, MN HO INT DIABETES CTR ID SPECIALTIES; SYSTEMS AB Randomized controlled trials (RCTs), such as the Diabetes Control and Complications Trial (DCCT), usually evaluate the efficacy of a single treatment strategy. The DCCT, for example, evaluates intensive diabetes management aimed at achieving glucose levels as close to normal as possible to modify specific pathophysiological outcomes-specifically, the development or worsening of microvascular disease. In contrast, longitudinal observational studies, such as the type II diabetes Patient Outcome Research Team (PORT) study, address medical effectiveness; that is, how well prevailing treatments work in clinical practice settings. The PORT relies heavily on patient-reported measures of general and diabetes-specific health status, in addition to using complications as major study outcomes. In the type II diabetes PORT, 4,000 patients with type II diabetes and a wide range of socioeconomic, demographic, and disease characteristics, from three widely dispersed geographic settings and varying systems of care, are being followed for a 2.5-year period. Data are collected from periodic self-administered patient questionnaires and from administrative data bases. In the PORT study, nonmutable coniounders, such as case-mix, and potentially mutable features, such as patients' preferences for treatment, health habits, regimen adherence, family support, and physician's interpersonal style, are carefully measured. The PORT study will examine the effectiveness of preventive care and established disease treatment in relation to eye, cardiovascular, and extremity disease, measuring and relating use of health-care services to patient outcomes. The results have the potential for maximizing quality of care and minimizing use of services in type II diabetes by matching physician-level profiles of patient outcomes with medical-care-process data and making this information accessible to practicing physicians. C1 TUFTS UNIV,SCH MED,BOSTON,MA 02111. UNIV MINNESOTA,SCH PUBL HLTH,MINNEAPOLIS,MN 55455. BOSTON UNIV,DEPT BIOMATH,BOSTON,MA 02215. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP GREENFIELD, S (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,PRIMARY CARE OUTCOMES RES INST,750 WASHINGTON ST,POB 345,BOSTON,MA 02111, USA. FU AHRQ HHS [5 R01-HS-06665-03] NR 13 TC 54 Z9 54 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 1994 VL 17 SU 1 BP 32 EP 39 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NP865 UT WOS:A1994NP86500007 PM 8088221 ER PT J AU WEXLER, HM MOLITORIS, E FINEGOLD, SM AF WEXLER, HM MOLITORIS, E FINEGOLD, SM TI IN-VITRO ACTIVITY OF GREPAFLOXACIN (OPC-17116) AGAINST ANAEROBIC-BACTERIA SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Note ID COMPARATIVE INVITRO ACTIVITIES; QUINOLONE AB In vitro activity of the quinolone grepafloxacin (OPC-17116) was compared with that of ciprofloxacin, fleroxacin, clindamycin, imipenem, and metronidazole by using the NCCLS-approved Brucella-base-laked blood agar dilution method and breakpoints, when available. Clindamycin, metronidazole, and imipenem inhibited greater than or equal to 98% of Bacteroides fragilis at the breakpoint; grepafloxacin, ciprofloxacin, and fleroxacin inhibited 83%, 6%, and 0, respectively, at 2 mu g/ml. Grepafloxacin inhibited 39% of other B. fragilis group species isolates (80) at breakpoint (less than or equal to 2 mu g/ml) compared with 100% for metronidazole and imipenem, 83% for clindamycin, 6% for ciprofloxacin, and 1% for fleroxacin. Grepafloxacin demonstrated substantially better activity against B. fragilis than did ciprofloxacin or fleroxacin; overall activity against anaerobes was marginally better than that of ciprofloxacin or fleroxacin. C1 VET ADM MED CTR,MED SERV,WADSWORTH DIV,LOS ANGELES,CA 91343. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. RP WEXLER, HM (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,MICROBIAL DIS RES LAB,RES SERV,WADSWORTH DIV,BLDG 304,LOS ANGELES,CA 90073, USA. NR 10 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUN PY 1994 VL 19 IS 2 BP 129 EP 133 DI 10.1016/0732-8893(94)90123-6 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA PD356 UT WOS:A1994PD35600009 PM 7805357 ER PT J AU NASU, M SUGAWARA, M AF NASU, M SUGAWARA, M TI EXOGENOUS FREE IODOTYROSINE INHIBITS IODIDE TRANSPORT THROUGH THE SEQUENTIAL INTRACELLULAR EVENTS SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID THYROID AUTO-REGULATION; CELLS; ADENOSINE-3',5'-MONOPHOSPHATE; THYROGLOBULIN; THYROTROPIN; MECHANISM; HORMONE AB We describe a new function of exogenous iodotyrosine as a regulator of iodide transport. Porcine thyroid follicles in culture were preincubated with 0-20 mu mol/l monoiodotyrosine or diiodotyrosine (DIT) in the presence of bovine thyrotropin (TSH) for 24 h; these iodotyrosines inhibited iodide uptake in a dose-response manner. Extracellular [I-125]DIT was actively transported to the thyroid follicle in the presence of TSH or (Bu)(2) cAMP. Inhibition of iodide uptake by iodotyrosine required preincubation with iodotyrosine in the presence of TSH; without TSH, iodotyrosine was ineffective. Follicles preincubated with DIT for 24 h inhibited TSH-mediated cAMP production, which is an important signal for iodide transport. Inhibition of iodide uptake and cAMP generation by iodotyrosine was negated characteristically by 3-nitro-L-tyrosine, an inhibitor of iodotyrosine deiodinase, or by methimazole, an inhibitor of thyroid peroxidase. Our findings suggest that iodotyrosine regulates iodide transport through the following sequential intracellular events: TSH-dependent iodotyrosine transport into the thyroid cell; deiodination of iodotyrosine and release in iodide; iodine organification by the peroxidase system; inhibition of cAMP generation by organified iodine; and inhibition of iodide transport. Thus, exogenous iodotyrosine can serve as an inhibitor of thyroid hormone formation only when TSH is present. C1 W LOS ANGELES VET AFFAIRS MED CTR,DIV ENDOCRINOL & METAB,RES SERV,LOS ANGELES,CA 90073. W LOS ANGELES VET AFFAIRS MED CTR,DIV ENDOCRINOL & METAB,MED SERV,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. NR 26 TC 2 Z9 2 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JUN PY 1994 VL 130 IS 6 BP 601 EP 607 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NT430 UT WOS:A1994NT43000012 PM 8205262 ER PT J AU NISHIKAWA, K LINSLEY, PS COLLINS, AB STAMENKOVIC, I MCCLUSKEY, RT ANDRES, G AF NISHIKAWA, K LINSLEY, PS COLLINS, AB STAMENKOVIC, I MCCLUSKEY, RT ANDRES, G TI EFFECT OF CTLA-4 CHIMERIC PROTEIN ON RAT AUTOIMMUNE ANTIGLOMERULAR BASEMENT-MEMBRANE GLOMERULONEPHRITIS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CTLA-4; CD28-B7 PATHWAY; GLOMERULONEPHRITIS; AUTOIMMUNITY ID T-CELL ACTIVATION; CD28; CTLA4IG; INVIVO AB The interaction of the T cell receptor with the antigen/major histocompatibility class II complex is insufficient to induce optimal T cell activation. Co-stimulatory signals, including those provided by CD28/CTLA-4 on T cells and B7 molecules (B7-1, -2 and -3) on antigen-presenting cells, are also required. CD28-B7 interactions can be blocked by a soluble human CTLA-4 chimeric protein (CTLA4Ig). We tested the effect of administration of CTLA4Ig on experimental anti-glomerular basement membrane (GBM) autoimmune glomerulonephritis in Wistar-Kyoto rats induced by immunization with bovine GBM. The disease is characterized by development of antibody to the alpha 3 chain of type IV collagen (Goodpasture's antigen), deposition of rat IgG in GBM, infiltration of the kidney by T cells and macrophages, severe crescent formation and renal failure leading to death in 5-6 weeks. Animals injected with human CTLA4Ig from day 0 to day 14 or to day 35 had reduced disease severity. Beneficial effects were observed even when injections were begun after the onset of glomerulonephritis on day 14. However, the rats developed antibody to the human CTLA4Ig, associated with reduction in levels of circulating CTLA4Ig. The results provide evidence for CD28/CTLA-4 signaling in rat autoimmune glomerulonephritis, and suggest that more effective inhibition of B7-dependent T cell activation, such as might be achieved with homologous CTLA4Ig, could be useful in the treatment of autoimmune diseases. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,SEATTLE,WA 98121. FU NIDDK NIH HHS [DK-36807] NR 12 TC 75 Z9 75 U1 1 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUN PY 1994 VL 24 IS 6 BP 1249 EP 1254 DI 10.1002/eji.1830240602 PG 6 WC Immunology SC Immunology GA NT243 UT WOS:A1994NT24300001 PM 8206086 ER PT J AU TOTH, TL LANZENDORF, SE SANDOW, BA VEECK, LL HASSEN, WA HANSEN, K HODGEN, GD AF TOTH, TL LANZENDORF, SE SANDOW, BA VEECK, LL HASSEN, WA HANSEN, K HODGEN, GD TI CRYOPRESERVATION OF HUMAN PROPHASE-I OOCYTES COLLECTED FROM UNSTIMULATED FOLLICLES SO FERTILITY AND STERILITY LA English DT Article DE IN VITRO MATURATION; OOCYTE; CRYOPRESERVATION; TRANSMISSION ELECTRON MICROSCOPY ID MOUSE OOCYTES; MEIOTIC SPINDLE; INVITRO; MATURATION AB Objective: To evaluate the cryopreservation of immature human oocytes obtained from unstimulated ovarian tissue. Design: Immature prophase I oocytes were obtained from unstimulated follicles and were either cryopreserved or cultured as controls. Cryopreservation was performed in a programmable freezing machine using one of two protocols. Method I (n = 133) used a one-step addition of cryoprotectant followed by a slow freeze and thaw protocol. With method II (n = 95),the cryoprotectant was added in a stepwise manner with cryopreservation performed in the presence of 0.2 M sucrose followed by rapid freezing and thawing. Setting: Basic research center at a medical school. Patients: Patients undergoing oophorectomy for nonovarian pathology. Main Outcome Measures: Rates of survival and maturation to metaphase II were compared between control oocytes and oocytes cryopreserved with methods I and II. Results: With method I, a survival rate of 15.6% was obtained with 58.3% of surviving oocytes reaching metaphase II after culture compared with 50.0% of nonfrozen control oocytes. Method II produced a survival rate of 43.3% with 27.3% maturing to metaphase II. Maturation of control oocytes for method II was 46.4%. Although the survival rate with method II was significantly higher than with method I, the rate of in vitro maturation to metaphase II showed no difference. Conclusions: These results demonstrate that human prophase I oocytes obtained from unstimulated antral follicles are capable of meiotic maturation after cryopreservation. C1 EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,DEPT OBSTET & GYNECOL,NORFOLK,VA 23507. MASSACHUSETTS GEN HOSP,VINCENT MEM GYNECOL SERV,BOSTON,MA. PORTSMOUTH NAVAL HOSP,DEPT OBSTET & GYNECOL,PORTSMOUTH,VA. NR 19 TC 77 Z9 81 U1 0 U2 1 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 1994 VL 61 IS 6 BP 1077 EP 1082 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA NN391 UT WOS:A1994NN39100013 PM 8194620 ER PT J AU OBERLEY, TD SCHULTZ, JL OBERLEY, LW AF OBERLEY, TD SCHULTZ, JL OBERLEY, LW TI IN-VITRO MODULATION OF ANTIOXIDANT ENZYME LEVELS IN NORMAL HAMSTER-KIDNEY AND ESTROGEN-INDUCED HAMSTER-KIDNEY TUMOR SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ANTIOXIDANT ENZYMES; MANGANESE SUPEROXIDE DISMUTASE; KIDNEY; TUMOR; DIETHYLSTILBESTROL; FREE RADICALS ID MANGANESE SUPEROXIDE-DISMUTASE; SYRIAN-HAMSTER; IMMUNOHISTOCHEMICAL LOCALIZATION; GLUTATHIONE-PEROXIDASE; LUNG FIBROBLASTS; CELLS; INVITRO; PROLIFERATION; DIFFERENTIATION; INDUCTION AB Antioxidant enzyme (AE) activities were studied in normal hamster kidney proximal tubules and in estrogen-induced hamster kidney cancer. In vivo, kidney tumor had lower activities of manganese superoxide dismutase (MnSOD), copper, zinc superoxide dismutase, catalase, and glutathione peroxidase than kidney proximal tubules. Differences in AE activities were, in general, maintained in tissue culture, with AE activities remaining low in tumor cells compared to normal cells. Normal proximal tubular cells showed significant induction of MnSOD activity as a function of time in culture or following exposure to diethylstilbestrol, a synthetic estrogen, while MnSOD activity remained low in tumor cells under these conditions. Our results suggest that antioxidant enzymes, particularly MnSOD, are regulated differently in estrogen-induced hamster kidney tumor cells than in normal kidney proximal tubular cells, demonstrating that cancers arising from hormonal influence have similar AE profiles to those previously described in cancers arising from viral or chemical etiologies. C1 UNIV WISCONSIN,SCH MED,DEPT PATHOL,MADISON,WI 53706. UNIV IOWA,COLL MED,RADIAT RES LAB,IOWA CITY,IA. RP OBERLEY, TD (reprint author), WILLIAM S MIDDLETON MEM VET ADM MED CTR,PATHOL & LAB MED SERV,2500 OVERLOOK TERRACE,MADISON,WI 53705, USA. FU NCI NIH HHS [CA 41267] NR 37 TC 20 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUN PY 1994 VL 16 IS 6 BP 741 EP 751 DI 10.1016/0891-5849(94)90189-9 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA NL951 UT WOS:A1994NL95100008 PM 8070677 ER PT J AU BLUMENTHAL, D AF BLUMENTHAL, D TI GROWING PAINS FOR NEW ACADEMIC-INDUSTRY RELATIONSHIPS SO HEALTH AFFAIRS LA English DT Article ID UNIVERSITY; BIOTECHNOLOGY; INNOVATION AB Five decades of almost unwavering federal support of university research in biomedicine have spawned a biotechnology revolution that holds dramatic promise for the public health and the U.S. economy. To make that promise a reality, the federal government now strongly encourages universities to facilitate the practical application of research results by participating in academic/industry relationships. These relationships are yielding important health and economic benefits, but the new economic entanglements of U.S. universities also could undermine the public trust that has sustained federal support of biomedical research. Thus, efforts to speed the transfer of technologies through academic/industry relationships may have enormous effects on the government/university partnership that gave birth to those technologies. 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 33 TC 26 Z9 26 U1 1 U2 3 PU PROJECT HOPE-HEALTH AFFAIRS PI SYRACUSE PA PO BOX 8015, SYRACUSE, NY 13217 SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SUM PY 1994 VL 13 IS 3 BP 176 EP 193 DI 10.1377/hlthaff.13.3.176 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA NZ611 UT WOS:A1994NZ61100017 PM 7927148 ER PT J AU GARBER, JE AF GARBER, JE TI MARKERS OF RISK FOR HUMAN MALIGNANCIES SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID TUMOR-SUPPRESSOR GENE; LI-FRAUMENI SYNDROME; NONPOLYPOSIS COLORECTAL-CANCER; ENDOCRINE NEOPLASIA TYPE-2A; MUIR-TORRE SYNDROME; P53 GENE; GERMLINE MUTATIONS; BREAST-CANCER; FAMILY HISTORY; COLON-CANCER C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CANC RISK & PREVENT PROGRAM,BOSTON,MA 02115. RP GARBER, JE (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 58 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 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1994 VL 8 IS 3 BP 471 EP 483 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA NR561 UT WOS:A1994NR56100003 PM 8707768 ER PT J AU HAYES, DF AF HAYES, DF TI TUMOR-MARKERS FOR BREAST-CANCER - CURRENT UTILITIES AND FUTURE-PROSPECTS SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID EPITHELIAL MEMBRANE ANTIGEN; AXILLARY MICRO-METASTESES; DUCTAL CARCINOMA INSITU; HER-2 NEU ONCOGENE; TERM FOLLOW-UP; PROGNOSTIC-SIGNIFICANCE; MONOCLONAL-ANTIBODIES; BONE-MARROW; ESTROGEN-RECEPTOR; FLOW-CYTOMETRY RP HAYES, DF (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CTR BREAST EVALUAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 116 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1994 VL 8 IS 3 BP 485 EP 506 PG 22 WC Oncology; Hematology SC Oncology; Hematology GA NR561 UT WOS:A1994NR56100004 PM 8707769 ER PT J AU STRAUSS, GM SKARIN, AT AF STRAUSS, GM SKARIN, AT TI USE OF TUMOR-MARKERS IN LUNG-CANCER SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID NEURON-SPECIFIC ENOLASE; SMALL-CELL-CARCINOMA; INTERNATIONAL STAGING SYSTEM; TISSUE POLYPEPTIDE ANTIGEN; KINASE-BB LEVELS; CARCINOEMBRYONIC ANTIGEN; MONOCLONAL-ANTIBODY; PROGNOSTIC FACTORS; DNA CONTENT; MONITORING PATIENTS C1 BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. RP STRAUSS, GM (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 109 TC 15 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1994 VL 8 IS 3 BP 507 EP 532 PG 26 WC Oncology; Hematology SC Oncology; Hematology GA NR561 UT WOS:A1994NR56100005 PM 8707770 ER PT J AU POSNER, MR MAYER, RJ AF POSNER, MR MAYER, RJ TI THE USE OF SEROLOGIC TUMOR-MARKERS IN GASTROINTESTINAL MALIGNANCIES SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID CARCINOEMBRYONIC ANTIGEN CEA; HUMAN COLORECTAL-CARCINOMA; SERUM CA 19-9; ALPHA-FETOPROTEIN; HEPATOCELLULAR-CARCINOMA; PANCREATIC-CANCER; HEPATIC RESECTION; ADJUVANT THERAPY; PROGNOSTIC VALUE; COLON-CANCER C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED ONCOL,BOSTON,MA 02115. RP POSNER, MR (reprint author), NEW ENGLAND DEACONESS HOSP,DEACONESS DANA FARBER ONCOL UNIT,DIV HEMATOL ONCOL,C106,CRI BLDG,BOSTON,MA 02215, USA. NR 87 TC 42 Z9 42 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1994 VL 8 IS 3 BP 533 EP 553 PG 21 WC Oncology; Hematology SC Oncology; Hematology GA NR561 UT WOS:A1994NR56100006 PM 8707771 ER PT J AU KANTOFF, PW TALCOTT, JA AF KANTOFF, PW TALCOTT, JA TI THE PROSTATE-SPECIFIC ANTIGEN - ITS USE AS A TUMOR-MARKER FOR PROSTATE-CANCER SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID DIGITAL RECTAL EXAMINATION; EXTERNAL BEAM RADIOTHERAPY; PREDICT PATHOLOGICAL STAGE; HUMAN SEMINAL PLASMA; RADICAL PROSTATECTOMY; RADIATION-THERAPY; CLINICAL STAGE; INTRAEPITHELIAL NEOPLASIA; PROGNOSTIC-SIGNIFICANCE; ACID-PHOSPHATASE RP KANTOFF, PW (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 66 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1994 VL 8 IS 3 BP 555 EP 572 PG 18 WC Oncology; Hematology SC Oncology; Hematology GA NR561 UT WOS:A1994NR56100007 PM 8707772 ER PT J AU HAYES, DF AF HAYES, DF TI TUMOR-MARKERS IN ADULT SOLID MALIGNANCIES - PREFACE SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Editorial Material 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 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD JUN PY 1994 VL 8 IS 3 BP R9 EP R10 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA NR561 UT WOS:A1994NR56100001 ER PT J AU UBEDA, M MATZILEVICH, MM ATUCHA, NM GARCIAESTAN, J QUESADA, T TANG, SS INGELFINGER, JR AF UBEDA, M MATZILEVICH, MM ATUCHA, NM GARCIAESTAN, J QUESADA, T TANG, SS INGELFINGER, JR TI RENIN AND ANGIOTENSINOGEN MESSENGER-RNA EXPRESSION IN THE KIDNEYS OF RATS SUBJECTED TO LONG-TERM BILE-DUCT LIGATION SO HEPATOLOGY LA English DT Article ID MESSENGER-RNA EXPRESSION; HEMODYNAMIC CHARACTERIZATION; HEPATORENAL-SYNDROME; RENAL HEMODYNAMICS; SODIUM-REGULATION; WATER-RETENTION; GENE-EXPRESSION; HEART-FAILURE; LIVER-DISEASE; CIRRHOSIS AB Activation of antinatriuretic systems such as the renin-angiotensin system, is of major importance in the pathogenesis of sodium retention in cirrhosis. In this study, we studied the intrarenal renin angiotensin system by measuring renin and angiotensinogen mRNA expression in the kidney of rats subjected to long-term bile duct ligation in a phase before the development of ascites, when sodium retention is already present. Experiments were performed in sham-operated and bile duct-ligated rats 3 wk after surgery. Balance studies showed lower sodium excretion and greater sodium retention in the bile duct-ligated rats compared with the control animals. Plasma renin activity (4.41 +/- 1.01 ng Angiotensin I/ml/hr in the bile duct-ligated group vs, 4.20 +/- 0.74 in the controls) and plasma renin concentration were not different between the two groups. However, plasma renin substrate was significantly decreased in bile duct-ligated animals. Total kidney renin mRNA was significantly higher in the bile duct-ligated animals (0.83 +/- 0.14 densitometric units vs. 0.44 +/- 0.04 in the controls), as determined on Northern-blot analysis and densitometric quantitation. Angiotensinogen mRNA expression in the kidneys of bile duct-ligated rats was significantly decreased (0.09 +/- 0.01 densitometric units) compared with that of the controls (0.21 +/- 0.03). These results indicate that sodium-retaining, nonascitic bile duct-ligated rats show abnormalities of the intrarenal renin angiotensin system that precede changes in plasma renin activity. Our data suggest that the intrarenal renin angiotensin system may participate in the initiation of the renal pathophysiological abnormalities present in bile duct-ligated rats. C1 FAC MED MURCIA,DEPT FISIOL,E-30100 MURCIA,SPAIN. RP UBEDA, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC ENDOCRINOL,DIV PEDIAT NEPHROL,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL 48455] NR 39 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1994 VL 19 IS 6 BP 1431 EP 1436 DI 10.1002/hep.1840190618 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NP547 UT WOS:A1994NP54700017 PM 8188173 ER PT J AU NANJI, AA ZHAO, SP SADRZADEH, SMH WAXMAN, DJ AF NANJI, AA ZHAO, SP SADRZADEH, SMH WAXMAN, DJ TI USE OF REVERSE TRANSCRIPTION-POLYMERASE CHAIN-REACTION TO EVALUATE IN-VIVO CYTOKINE GENE-EXPRESSION IN RATS FED ETHANOL FOR LONG PERIODS SO HEPATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ALCOHOLIC LIVER-DISEASE; GROWTH-FACTOR-BETA; FACTOR-ALPHA; ENDOTOXIN; INJURY; INTERLEUKIN-1; HEPATITIS; CLONING; CELL AB We evaluated the expression of interleukin-1 alpha interleukin-1 beta, tumor necrosis factor-alpha and transforming growth factor-beta mRNAs in the intragastric feeding rat model of alcoholic liver disease. Rats were fed different diets for periods of 2 or 4 wk. Animals fed saturated fat and ethanol and the corn oil-dextrose control group had no liver injury, whereas animals fed corn oil and ethanol showed pathologic changes. RNA was extracted from the livers at the time of killing, reverse-transcribed and amplified; polymerase chain reaction products were subjected to electrophoresis on agarose gel. Interleukin-1 alpha mRNA was present in all groups at 2 and 4 wk; interleukin-1 beta and transforming growth factor-beta mRNAs were present in all groups at 4 wk. Tumor necrosis factor-alpha mRNA was absent in all groups at 2 wk but was present in the corn oil-ethanol group only at 4 wk. Because pathological liver injury was evident in the corn oil-ethanol group by 4 wk, the presence of tumor necrosis factor-cu mRNA at this time suggests a pathogenetic role for tumor necrosis factor-alpha in alcohol-induced liver injury. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. RP NANJI, AA (reprint author), NEW ENGLAND DEACONESS HOSP,DEPT PATHOL,M323,185 PILRIM RD,BOSTON,MA 02215, USA. NR 35 TC 99 Z9 107 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1994 VL 19 IS 6 BP 1483 EP 1487 DI 10.1016/0270-9139(94)90246-1 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NP547 UT WOS:A1994NP54700024 PM 8188180 ER PT J AU SEMINARA, SB DRYJA, TP AF SEMINARA, SB DRYJA, TP TI UNBIASED TRANSMISSION OF MUTANT ALLELES AT THE HUMAN RETINOBLASTOMA LOCUS SO HUMAN GENETICS LA English DT Article ID ONCOGENIC POINT MUTATIONS; SUSCEPTIBILITY GENE; PCR; AMPLIFICATION; POLYMORPHISMS; PENETRANCE; SEQUENCE; RFLP AB The preferential transmission of the mutant allele to offspring from fathers who carry a germline mutation in the retinoblastoma gene was examined by analyzing 46 consecutive pedigrees. Among 75 offspring from 29 fathers, the ratio of carriers to noncarriers was 49%. Among the 106 offspring from 55 mothers the ratio was 57%. Neither ratio differs statistically from the expected 50%. When the analysis was limited to only those families with low-penetrance retinoblastoma, we still did not observe a biased transmission of alleles from fathers, although mothers did have an excess of carrier offspring of borderline statistical significance (the P-value was approximately 0.03). While we cannot rule out a biased transmission of alleles from some parents, there appears to be no such bias overall. C1 MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NEI NIH HHS [EY05321] NR 15 TC 6 Z9 6 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 JUN PY 1994 VL 93 IS 6 BP 629 EP 634 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA NP565 UT WOS:A1994NP56500004 PM 8005586 ER PT J AU ESTEBAN, J ROSEN, DR BOWLING, AC SAPP, P MCKENNAYASEK, D OREGAN, JP BEAL, MF HORVITZ, HR BROWN, RH AF ESTEBAN, J ROSEN, DR BOWLING, AC SAPP, P MCKENNAYASEK, D OREGAN, JP BEAL, MF HORVITZ, HR BROWN, RH TI IDENTIFICATION OF 2 NOVEL MUTATIONS AND A NEW POLYMORPHISM IN THE GENE FOR CU/ZN SUPEROXIDE-DISMUTASE IN PATIENTS WITH AMYOTROPHIC-LATERAL-SCLEROSIS SO HUMAN MOLECULAR GENETICS LA English DT Note C1 MASSACHUSETTS GEN HOSP E,CECIL B DAY LAB NEUROMUSCULAR RES,BOSTON,MA 02129. INST SALUD CARLOS 3,CTR INVEST CLIN,SERV NEUROL,E-28019 MADRID,SPAIN. MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,BOSTON,MA 02114. MIT,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. FU NIAAA NIH HHS [NIAAG05134]; NINDS NIH HHS [1F32NS09263-01A1, 1PO1NS31248-01] NR 13 TC 79 Z9 80 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1994 VL 3 IS 6 BP 997 EP 998 DI 10.1093/hmg/3.6.997 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NU390 UT WOS:A1994NU39000027 PM 7951252 ER PT J AU MULLIGAN, LM ENG, C HEALEY, CS PONDER, MA FELDMAN, GL LI, PZ JACKSON, CE PONDER, BAJ AF MULLIGAN, LM ENG, C HEALEY, CS PONDER, MA FELDMAN, GL LI, PZ JACKSON, CE PONDER, BAJ TI A DE-NOVO MUTATION OF THE RET PROTOONCOGENE IN A PATIENT WITH MEN 2A SO HUMAN MOLECULAR GENETICS LA English DT Note ID MULTIPLE ENDOCRINE NEOPLASIA; MEDULLARY-THYROID CARCINOMA; PROTOONCOGENE; LINKAGE; REPEAT; LOCUS C1 UNIV CAMBRIDGE,DEPT PATHOL,CRC,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 1QP,CAMBS,ENGLAND. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HENRY FORD HOSP,CTR MED GENET BIRTH DEFECTS,DETROIT,MI 48202. HENRY FORD HOSP,DEPT MED,DETROIT,MI 48202. OI Eng, Charis/0000-0002-3693-5145 NR 14 TC 30 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1994 VL 3 IS 6 BP 1007 EP 1008 DI 10.1093/hmg/3.6.1007 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NU390 UT WOS:A1994NU39000032 PM 7951212 ER PT J AU RAO, A AF RAO, A TI NF-ATP - A TRANSCRIPTION FACTOR REQUIRED FOR THE COORDINATE INDUCTION OF SEVERAL CYTOKINE GENES SO IMMUNOLOGY TODAY LA English DT Review ID ACTIVATED T-CELLS; CYCLOSPORINE-A INHIBIT; FACTOR-ALPHA GENE; NUCLEAR FACTOR; SIGNAL-TRANSDUCTION; INTERLEUKIN-2 GENE; KAPPA-B; PROMOTER; BINDING; PROTEIN AB The transcription factor NF-ATp is a target in activated T cells for the calcium-regulated phosphatase calcineurin, and is therefore a secondary target for the immunosuppressive drugs cyclosporin A and FK506. Here, Anjana Rao describes how NF-ATp cooperates with Fos- and Jun-family proteins to mediate transcription of the interleukin 2 gene, and how it may participate in the calcium-dependent transcription of other cytokine genes in several types of immune-system cells. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02115. RP RAO, A (reprint author), HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA42471]; NIGMS NIH HHS [GM46227] NR 45 TC 495 Z9 500 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JUN PY 1994 VL 15 IS 6 BP 274 EP 281 DI 10.1016/0167-5699(94)90007-8 PG 8 WC Immunology SC Immunology GA NQ722 UT WOS:A1994NQ72200007 PM 8068174 ER PT J AU DERESIEWICZ, RL FLAXENBURG, JA CHAN, M FINBERG, RW KASPER, DL AF DERESIEWICZ, RL FLAXENBURG, JA CHAN, M FINBERG, RW KASPER, DL TI INTRACELLULAR EXPRESSION OF TOXIC SHOCK SYNDROME TOXIN-1 IN SACCHAROMYCES-CEREVISIAE SO INFECTION AND IMMUNITY LA English DT Article ID STAPHYLOCOCCUS-AUREUS; DIPHTHERIA-TOXIN; A-CHAIN; CELLS; NUCLEOTIDE; MUTATIONS AB In order to search for an occult cytotoxic enzymatic activity of the toxic shock syndrome toxin 1 (TSST-1), we placed the gene encoding TSST-1 (tstH) under the control of an inducible promoter in the eukaryotic yeast Saccharomyces cerevisiae. Under similar circumstances, the known bacterial enzymatic cytotoxins Shiga-like toxin and diphtheria toxin are both highly lethal to the yeast host. Although full-length stable TSST-1 was demonstrated within the yeast cells and although it retained mitogenicity for human T cells, it had no apparent effect on the yeast cells' growth kinetics or on their gross morphology. Retrieval and sequencing of the toxin gene revealed the wild-type sequence throughout, thus demonstrating that the apparent lack of toxicity for the yeast cells was not due to a serendipitous attenuating mutation within the coding region of the toxin gene. Similar results obtained after a second transformation of the same strain and after transformation of an unrelated strain demonstrate that neither chance permissive host mutation nor intrinsic host resistance was likely to have obscured an existing cytotoxic property of TSST-1. We conclude that TSST-1 probably does not possess a discrete enzymatic property cytotoxic for eukaryotic cells. C1 BRIGHAM & WOMENS HOSP,CHANNING LAB,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV INFECT DIS,BOSTON,MA 02115. DANA FARBER CANC INST,INFECT DIS LAB,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV INFECT DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 NR 23 TC 7 Z9 7 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 JUN PY 1994 VL 62 IS 6 BP 2202 EP 2207 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NM782 UT WOS:A1994NM78200009 PM 8188341 ER PT J AU BAKER, PJ HRABA, T TAYLOR, CE STASHAK, PW FAUNTLEROY, MB ZAHRINGER, U TAKAYAMA, K SIEVERT, TR HRONOWSKI, XP COTTER, RJ PEREZPEREZ, G AF BAKER, PJ HRABA, T TAYLOR, CE STASHAK, PW FAUNTLEROY, MB ZAHRINGER, U TAKAYAMA, K SIEVERT, TR HRONOWSKI, XP COTTER, RJ PEREZPEREZ, G TI MOLECULAR-STRUCTURES THAT INFLUENCE THE IMMUNOMODULATORY PROPERTIES OF THE LIPID-A AND INNER-CORE REGION OLIGOSACCHARIDES OF BACTERIAL LIPOPOLYSACCHARIDES SO INFECTION AND IMMUNITY LA English DT Article ID III PNEUMOCOCCAL POLYSACCHARIDE; SUPPRESSOR T-CELLS; ANTIBODY-PRODUCING CELLS; GRAM-NEGATIVE BACTERIA; A-SUBUNIT ANALOGS; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; HELICOBACTER-PYLORI; CELLULAR LEVEL; MICE AB The relationship between chain length as well as the position of fatty acyl groups to the ability of lipid A to abolish the expression of suppressor T-cell (Ts) activity was examined. Fatty acyl chain lengths of C-12 to C-14, as in the lipid A of Escherichia coli and Salmonella minnesota, appear to be optimal for this bioactivity, since lipid A preparations with fatty acyl groups of relatively short chain length (C-10 to C-12 for Pseudomonas aeruginosa and Chromobacterium violaceum) or predominantly long chain length (C-18 for Helicobacter pylori) are without effect. The presence of an acyloxyacyl group of appropriate chain length at the 3' position of the glucosamine disaccharide backbone of lipid A also plays a decisive role. By contrast, the lipid A proximal inner core region oligosaccharides of some bacterial lipopolysaccharides increase the expression of Ts activity; this is due mainly to the capacity of such oligosaccharides, which are relatively conserved in structure among gram-negative bacteria, to enlarge or expand upon the population of CD8(+) Ts generated during the course of a normal antibody response to unrelated microbial antigens. The minimal structure required for the expression of the added immunosuppression observed appears to be a hexasaccharide containing one 2-keto-3-deoxyoctonate residue, two glucose residues, and three heptose residues to which are attached two pyrophosphorylethanolamine groups. The relevance of these findings to virulence and to the pathogenesis of gram-negative infections is discussed. C1 NIAID, TWINBROOK RES FACIL 2, IMMUNOGENET LAB, ROCKVILLE, MD USA. FORSCHUNGSINST BORSTEL, INST EXPTL BIOL & MED, W-2061 BORSTEL, GERMANY. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MYCOBACTERIOL RES LAB, MADISON, WI 53705 USA. UNIV WISCONSIN, COLL AGR & LIFE SCI, DEPT BACTERIOL, MADISON, WI 53706 USA. JOHNS HOPKINS SCH MED, DEPT PHARMACOL & MOLEC SCI, BALTIMORE, MD 21205 USA. VANDERBILT UNIV, SCH MED, DEPT MED, DIV INFECT DIS, NASHVILLE, TN 37232 USA. FU NIGMS NIH HHS [GM-36054] NR 60 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1994 VL 62 IS 6 BP 2257 EP 2269 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NM782 UT WOS:A1994NM78200017 PM 8188347 ER PT J AU HANDT, LK FOX, JG DEWHIRST, FE FRASER, GJ PASTER, BJ YAN, LL ROZMIAREK, H RUFO, R STALIS, IH AF HANDT, LK FOX, JG DEWHIRST, FE FRASER, GJ PASTER, BJ YAN, LL ROZMIAREK, H RUFO, R STALIS, IH TI HELICOBACTER-PYLORI ISOLATED FROM THE DOMESTIC CAT - PUBLIC-HEALTH IMPLICATIONS SO INFECTION AND IMMUNITY LA English DT Article ID ACTIVE CHRONIC GASTRITIS; SMALL ANIMAL-MODEL; CAMPYLOBACTER-PYLORI; RHESUS-MONKEY; INFECTION; MUSTELAE; TRANSMISSION; STOMACH; BACTERIUM; PHYLOGENY AB Helicobacter pylori has been directly linked with active chronic gastritis, peptic ulceration, and gastric adenocarcinoma in humans. Although a substantial portion of the human population is colonized with H. pylori, the patterns of transmission of the organism remain in doubt, and reservoir hosts have not been identified. This study documents the isolation of H. pylori from domestic cats obtained from a commercial vendor. The isolation of H. pylori from these cats was confirmed by morphologic and biochemical evaluations, fatty acid analysis, and 16S rRNA sequence analysis. H. pylori was cultured from 6 cats and organisms compatible in appearance with H. pylori were observed in 15 additional cats by histologic examination. In most animals, H. pylori was present in close proximity to mucosal epithelial cells or in mucus layers of the glandular or surface epithelium. Microscopically, H. pylori-infected cat stomachs contained a mild to severe diffuse lymphoplasmacytic infiltrate with small numbers of neutrophils and eosinophils in the subglandular and gastric mucosae. Lymphoid follicles were also noted, particularly in the antrum, and often displaced glandular mucosal tissue. Thus, the domestic cat may be a potential model for H. pylori disease in humans. Also, the isolation of H. pylori from domestic cats raises the possibility that the organism may be a zoonotic pathogen, with transmission occurring from cats to humans. C1 MIT,DIV COMPARAT MED,CAMBRIDGE,MA 02139. UNIV PENN,ANIM RESOURCES LAB,PHILADELPHIA,PA 19104. UNIV PENN,SCH VET MED,DEPT VET PATHOBIOL,PHILADELPHIA,PA 19104. FORSYTH DENT CTR,DEPT MOLEC GENET,BOSTON,MA 02215. FU NCI NIH HHS [CA-26731, CA-28842]; NCRR NIH HHS [RR-01046] NR 40 TC 184 Z9 188 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1994 VL 62 IS 6 BP 2367 EP 2374 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NM782 UT WOS:A1994NM78200031 PM 8188360 ER PT J AU SMITH, DJ AKITA, H KING, WF TAUBMAN, MA AF SMITH, DJ AKITA, H KING, WF TAUBMAN, MA TI PURIFICATION AND ANTIGENICITY OF A NOVEL GLUCAN-BINDING PROTEIN OF STREPTOCOCCUS-MUTANS SO INFECTION AND IMMUNITY LA English DT Article ID SALIVARY IGA ANTIBODY; SEQUENCE-ANALYSIS; GLUCOSYLTRANSFERASE GENE; SOBRINUS; DOMAIN; FRUCTOSYLTRANSFERASE; INGBRITT; SUCROSE AB A novel glucan-binding protein (GBP) having an apparent molecular mass of 59 kDa (GBP(59)) has been purified from Streptococcus mutans SJ by a combination of affinity chromatography on alpha-1,6-linked glucan, gel filtration chromatography, and ion-exchange chromatography. GBP(59) was distinct from the quantitatively predominant S. mutans GBP (GBP(74)) on the basis of size, elution position in a salt gradient, and antigenicity. Rat antisera to purified GBP(59) and GBP(74) did not cross-react. GBP(59) is apparently immunogenic in humans, since immunoglobulin A (IgA) antibody in 20 of 24 adult parotid saliva samples was shown to react with GBP(59) in an enzyme-linked immunosorbent assay. The glucan-binding activity of GBP(59) was confirmed by anti-GBP(59) immunogold labelling of Sephadex G-50 that had been preincubated with S. mutans culture supernatant. GBP(59) could be detected in culture supernatants of all laboratory strains of S. mutans (e.g., Ingbritt), as well as all strains of S. mutans that had been recently isolated from young children. GBP(59) was often the only component in protease inhibitor-containing 4-h S. mutans culture supernatants that reacted with human parotid salivary IgA antibody in Western blot (immunoblot) analyses. These studies suggest that GBP(59) is a structurally and antigenically distinct S. mutans GBP that can elicit significant levels of salivary IgA antibody in humans. RP SMITH, DJ (reprint author), FORSYTH DENT CTR,DEPT IMMUNOL,140 FENWAY,BOSTON,MA 02115, USA. FU NIDCR NIH HHS [DE-04733, DE-06153] NR 37 TC 58 Z9 64 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 JUN PY 1994 VL 62 IS 6 BP 2545 EP 2552 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NM782 UT WOS:A1994NM78200054 PM 8188378 ER PT J AU DHANANI, S HUANG, M WANG, JY DUBINETT, SM AF DHANANI, S HUANG, M WANG, JY DUBINETT, SM TI INTERFERON-ALPHA INHIBITS MURINE MACROPHAGE TRANSFORMING GROWTH-FACTOR-BETA MESSENGER-RNA EXPRESSION SO INFLAMMATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; TOXIC T-CELLS; EXTRACELLULAR-MATRIX; TGF-BETA; THYMOCYTE PROLIFERATION; PULMONARY FIBROSIS; FACTOR-BETA-1 GENE; KILLER CELLS; GENERATION; COLLAGEN AB Transforming growth factor-beta (TGF-beta), a multifunctional polypeptide is produced by a wide variety of cells and regulates a broad array of physiological and pathological functions. TGF-beta appears to play a central role in pulmonary fibrosis and may contribute to tumor-associated immunosuppression. Alveolar macrophages are a rich source of TGF-beta and are intimately involved in lung inflammation. We therefore chose to study TGF-beta regulation in murine alveolar macrophages as well as an immortalized peritoned macrophage cell line (IC-21). Murine macrophages were incubated with cytokines to evaluate their role in regulating TGF-beta mRNA expression. We conclude that IFN-alpha downregulates TGF-beta mRNA expression in murine macrophages. C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP DHANANI, S (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DIV PULM & CRIT CARE MED,LOS ANGELES,CA 90073, USA. NR 43 TC 18 Z9 19 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0360-3997 J9 INFLAMMATION JI Inflammation PD JUN PY 1994 VL 18 IS 3 BP 301 EP 309 DI 10.1007/BF01534271 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA NQ871 UT WOS:A1994NQ87100005 PM 8088926 ER PT J AU SCAVONE, C MCKEE, M NATHANSON, JA AF SCAVONE, C MCKEE, M NATHANSON, JA TI MONOAMINE UPTAKE IN INSECT SYNAPTOSOMAL PREPARATIONS SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE TRANSPORTER; DOPAMINE; OCTOPAMINE; REUPTAKE; MONAMINE; SYNAPTOSOME ID SENSITIVE ADENYLATE-CYCLASE; H-3 COCAINE BINDING; PHARMACOLOGICAL CHARACTERIZATION; SEROTONIN TRANSPORTER; OCTOPAMINE RECEPTORS; DOPAMINE TRANSPORTER; LOCUSTA-MIGRATORIA; NERVOUS-TISSUE; CLONING; EXPRESSION AB Biochemical studies of mammalian synaptosomal nerve fractions indicate the existence of multiple transporter proteins important for the termination of synaptic transmission by each of several monoamines. In insects, however, data on monoamine uptake has been limited to the study of whole tissue preparations, making it unclear whether neuronal (as opposed to glial) uptake is a significant mechanism in the insect. The present experiments elucidate the difficulties that have limited the use of insect synaptosomal preparations for characterizing amine reuptake. Key procedural improvements, including the utilization of carrier protein for tracer separation and the use of receptor antagonists to decrease non-specific membrane binding are described. With these and other modifications, reproducible sodium-dependent and cocaine-inhibitable dopamine and octopamine uptake are described in synaptosomal-containing preparations from insect brain and ganglia. These studies therefore support the existence of specific Na+-dependent uptake mechanisms in insect neurons. C1 HARVARD UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROPHARMACOL RES LAB,BOSTON,MA 02114. OI Scavone, Cristoforo/0000-0002-1206-0882 FU NIAID NIH HHS [AI29533] NR 29 TC 13 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JUN PY 1994 VL 24 IS 6 BP 589 EP 597 DI 10.1016/0965-1748(94)90095-7 PG 9 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA NT675 UT WOS:A1994NT67500007 PM 8044174 ER PT J AU HOOPER, DC RUBIN, DH CEBRA, JJ AF HOOPER, DC RUBIN, DH CEBRA, JJ TI SPONTANEOUS PROLIFERATION OF PEYERS PATCH CELLS IN-VITRO SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE AUTOLOGOUS MIXED LYMPHOCYTE REACTION; DENDRITIC CELLS; MUCOSAL IMMUNITY; T-CELLS ID AUTOREACTIVE T-CELLS; AUTOLOGOUS ERYTHROCYTES; LYMPHOID-TISSUES; DENDRITIC CELLS; CLONAL DELETION; SELF-TOLERANCE; LYMPHOCYTES-T; B-CELLS; ANTIGEN; MOUSE AB Under normal circumstances most lymphoid cell populations do not exhibit strong proliferative reactions in culture unless provoked by antigen or mitogen. The autologous mixed lymphocyte reaction (AMLR) mediated by adult T cells is a relatively weak proliferative response that occurs in the absence of known heterologous stimuli. In this investigation we demonstrate that Peyer's patch (PP) cells possess an inherent capacity to commence dividing in vitro and to display an exceptionally vigorous AMLR. The magnitude and kinetics of this spontaneous proliferation resemble that of a secondary response to a strong mucosal immunogen such as reovirus type 1/Lang. Analysis of the cellular components of the PP cultures implicates CD4+CD8- T cells as the major responding population and dendritic cells (DC) as stimulators. Mixing experiments indicate that spleen contains a cell population which can stimulate PP T cells, albeit to a lesser extent than PP cells. Similarly, splenic T cells have a reduced but significant capacity to respond to PP DC, in comparison to PP T cells. These differences suggest the possibility that there may be a decreasing gradient of antigenicity between the gut and the spleen which is reflected in the spontaneous activity of PP versus splenic T cells in vitro. We propose that PP cells are in fact responding in vitro to heterologous antigens derived from food, enteric microbes and other environmental sources. This notion is supported by the observation that PP cells from antigen-minimized germ-free mice fail to proliferate spontaneously in culture. C1 UNIV PENN,DEPT BIOL,LEIDY LAB BIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. OI Hooper, Douglas/0000-0002-8578-5104 FU NIAID NIH HHS [AI-17997, AI-23970] NR 40 TC 12 Z9 12 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 1994 VL 6 IS 6 BP 873 EP 880 DI 10.1093/intimm/6.6.873 PG 8 WC Immunology SC Immunology GA NT226 UT WOS:A1994NT22600009 PM 8086375 ER PT J AU VONDEIMLING, A NAGEL, J BENDER, B LENARTZ, D SCHRAMM, J LOUIS, DN WIESTLER, OD AF VONDEIMLING, A NAGEL, J BENDER, B LENARTZ, D SCHRAMM, J LOUIS, DN WIESTLER, OD TI DELETION MAPPING OF CHROMOSOME-19 IN HUMAN GLIOMAS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GENE; HETEROZYGOSITY; OLIGODENDROGLIOMAS; ASTROCYTOMAS; LOCI AB There is evidence that a putative glioma tumor suppressor locus resides on the long arm of chromosome 19. We present data on 161 gliomas from 156 patients, which were studied by microsatellite analysis for loss of heterozygosity (LOH) on chromosome 19. Eight loci on the long arm and 2 loci on the short arm of chromosome 19 were examined. LOH on 19q was observed in 3/19 astrocytomas (WHO grade II), 12/27 anaplastic astrocytomas (WHO grade III), 16/76 cases of glioblastoma multiforme WHO (grade IV), 4/9 oligodendrogliomas (WHO grade II), 3/5 anaplastic oligodendrogliomas (WHO grade III), 5/9 mixed oligo-astrocytomas (WHO grade II) and 8/10 anaplastic oligo-astrocytomas (WHO grade III). While 31 of the tumors with LOH on chromosomal arm 19q exhibited allelic loss at every informative locus, 20 tumors showed terminal or interstitial deletions. In contrast to astrocytomas and glioblastomas, tumors with an oligodendroglial component had predominantly lost the entire long arm of chromosome 19. The common region of overlap in gliomas was located on 19q13.2-q13.4 between the markers D19S178 and D19S180. Our data confirm the involvement of a putative tumor suppressor gene on chromosomal arm 19q in gliomas and assign this gene to 19q13.2-q13.4. (C) 1994 Wiley-Liss, Inc. C1 UNIV BONN KLINIKEN,INST NEUROPATHOL,BONN,GERMANY. NEUROCHIRURG KLIN,COLOGNE,GERMANY. UNIV BONN,NEUROCHIRURG KLIN,BONN,GERMANY. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA 02114. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X NR 22 TC 72 Z9 72 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 1994 VL 57 IS 5 BP 676 EP 680 DI 10.1002/ijc.2910570511 PG 5 WC Oncology SC Oncology GA NN912 UT WOS:A1994NN91200010 PM 8194874 ER PT J AU ENDO, EG MEAD, MD AF ENDO, EG MEAD, MD TI THE MANAGEMENT OF TRAUMATIC HYPHEMA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP ENDO, EG (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 1 EP 7 DI 10.1097/00004397-199403430-00003 PG 7 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200002 PM 7960507 ER PT J AU LEE, SY PAVANLANGSTON, D AF LEE, SY PAVANLANGSTON, D TI ROLE OF ACYCLOVIR IN THE TREATMENT OF HERPES-SIMPLEX VIRUS KERATITIS SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP LEE, SY (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 19 Z9 19 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 9 EP 18 DI 10.1097/00004397-199403430-00004 PG 10 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200003 PM 7960531 ER PT J AU PINEDA, R DOHLMAN, CH AF PINEDA, R DOHLMAN, CH TI THE ROLE OF STEROIDS IN THE MANAGEMENT OF ACANTHAMOEBA-KERATITIS, FUNGAL KERATITIS, AND EPIDEMIC KERATOCONJUNCTIVITIS SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP PINEDA, R (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 5 U1 1 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 19 EP 31 DI 10.1097/00004397-199403430-00005 PG 13 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200004 PM 7960514 ER PT J AU JAIN, VK LAWRENCE, M AF JAIN, VK LAWRENCE, M TI PERIBULBAR VERSUS RETROBULBAR ANESTHESIA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP JAIN, VK (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 33 EP 42 DI 10.1097/00004397-199403430-00006 PG 10 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200005 PM 7960526 ER PT J AU MCMILLAN, JJ MEAD, MD AF MCMILLAN, JJ MEAD, MD TI PROPHYLACTIC SUBCONJUNCTIVAL ANTIBIOTICS AFTER CATARACT-EXTRACTION - EVALUATION OF THEIR DESIRABILITY AND EFFICACY SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP MCMILLAN, JJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,23 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 43 EP 49 DI 10.1097/00004397-199403430-00007 PG 7 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200006 PM 7960527 ER PT J AU NAVON, SE ADAMIS, AP AF NAVON, SE ADAMIS, AP TI SAFETY DURING THE TRANSITION TO PHACOEMULSIFICATION - A SURVEY SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP NAVON, SE (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 51 EP 65 DI 10.1097/00004397-199403430-00008 PG 15 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200007 PM 7960528 ER PT J AU BERESTKA, JS RIZZO, JF AF BERESTKA, JS RIZZO, JF TI CONTROVERSY IN THE MANAGEMENT OF TRAUMATIC OPTIC NEUROPATHY SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP BERESTKA, JS (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 18 Z9 18 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 87 EP 96 DI 10.1097/00004397-199403430-00010 PG 10 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200009 PM 7960530 ER PT J AU MARCUS, DM DAMICO, DJ MUKAI, S AF MARCUS, DM DAMICO, DJ MUKAI, S TI PNEUMATIC RETINOPEXY VERSUS SCLERAL BUCKLING FOR REPAIR OF PRIMARY RHEGMATOGENOUS RETINAL-DETACHMENT SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP MARCUS, DM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 97 EP 108 DI 10.1097/00004397-199403430-00011 PG 12 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200010 PM 7960532 ER PT J AU SAMY, CN GRAGOUDAS, ES AF SAMY, CN GRAGOUDAS, ES TI LASER PHOTOCOAGULATION TREATMENT OF CENTRAL SEROUS CHORIORETINOPATHY SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP SAMY, CN (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 109 EP 119 DI 10.1097/00004397-199403430-00012 PG 11 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200011 PM 7960508 ER PT J AU PIERCE, EA MUKAI, S AF PIERCE, EA MUKAI, S TI CONTROVERSIES IN THE MANAGEMENT OF RETINOPATHY OF PREMATURITY SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP PIERCE, EA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. OI Pierce, Eric/0000-0002-2354-4102 NR 0 TC 5 Z9 5 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 121 EP 148 DI 10.1097/00004397-199403430-00013 PG 28 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200012 PM 7960509 ER PT J AU SMITH, SD NETLAND, PA AF SMITH, SD NETLAND, PA TI THE ROLE OF LASER TRABECULOPLASTY AS PRIMARY THERAPY FOR OPEN-ANGLE GLAUCOMA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP SMITH, SD (reprint author), MASSACHUSETTS EYE & EAR INFIRM,GLAUCOMA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 149 EP 161 DI 10.1097/00004397-199403430-00014 PG 13 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200013 PM 7960510 ER PT J AU MCHAM, ML MIGDAL, CS NETLAND, PA AF MCHAM, ML MIGDAL, CS NETLAND, PA TI EARLY TRABECULECTOMY IN THE MANAGEMENT OF PRIMARY OPEN-ANGLE GLAUCOMA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP MCHAM, ML (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 163 EP 172 DI 10.1097/00004397-199403430-00015 PG 10 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200014 PM 7960511 ER PT J AU GROSSKREUTZ, C NETLAND, PA AF GROSSKREUTZ, C NETLAND, PA TI LOW-TENSION GLAUCOMA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP GROSSKREUTZ, C (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 22 Z9 22 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 173 EP 185 DI 10.1097/00004397-199403430-00016 PG 13 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200015 PM 7960512 ER PT J AU BRODY, J WALLER, S WAGONER, M AF BRODY, J WALLER, S WAGONER, M TI CORNEAL TOPOGRAPHY - HISTORY, TECHNIQUE, AND CLINICAL USES SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP BRODY, J (reprint author), MASSACHUSETTS EYE & EAR INFIRM,CORNEA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 197 EP 207 DI 10.1097/00004397-199403430-00018 PG 11 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200017 PM 7960515 ER PT J AU FOSTER, CS DUTT, JE RICE, BA KUPFERMAN, AE LANE, L AF FOSTER, CS DUTT, JE RICE, BA KUPFERMAN, AE LANE, L TI CONJUNCTIVAL EPITHELIAL BASEMENT-MEMBRANE ZONE IMMUNOHISTOLOGY - NORMAL AND INFLAMED CONJUNCTIVA SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP FOSTER, CS (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 209 EP 214 DI 10.1097/00004397-199403430-00019 PG 6 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200018 PM 7960516 ER PT J AU PARK, SS DAMICO, DJ FOSTER, CS AF PARK, SS DAMICO, DJ FOSTER, CS TI THE ROLE OF INVASIVE DIAGNOSTIC TESTING IN INFLAMMATORY EYE DISEASES SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP PARK, SS (reprint author), MASSACHUSETTS EYE & EAR INFIRM,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 229 EP 238 DI 10.1097/00004397-199403430-00021 PG 10 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200020 PM 7960518 ER PT J AU FINKELSTEIN, M JAKOBIEC, FA AF FINKELSTEIN, M JAKOBIEC, FA TI LABORATORY EVALUATION OF OCULAR AND ADNEXAL LYMPHOID LESIONS SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP FINKELSTEIN, M (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 283 EP 292 DI 10.1097/00004397-199403430-00026 PG 10 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200025 PM 7960523 ER PT J AU LEVIN, LA LESSELL, S AF LEVIN, LA LESSELL, S TI MAGNETIC-RESONANCE ANGIOGRAPHY SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP LEVIN, LA (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,NEROOPTHALMOL UNIT,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 293 EP 303 DI 10.1097/00004397-199403430-00027 PG 11 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200026 PM 7960524 ER PT J AU JAKOBIEC, FA ADAMIS, AP VOLPE, NJ AF JAKOBIEC, FA ADAMIS, AP VOLPE, NJ TI CONTROVERSIES IN OPHTHALMOLOGY - CURRENT THERAPIES AND EMERGING TECHNOLOGIES - PREFACE SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Editorial Material RP JAKOBIEC, FA (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP R19 EP R19 DI 10.1097/00004397-199403430-00002 PG 1 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200001 ER PT J AU BERRA, A RODRIGUEZ, A HEILIGENHAUS, A PAZOS, B VANROOIJEN, N FOSTER, CS AF BERRA, A RODRIGUEZ, A HEILIGENHAUS, A PAZOS, B VANROOIJEN, N FOSTER, CS TI THE ROLE OF MACROPHAGES IN THE PATHOGENESIS OF HSV-1 INDUCED CHORIORETINITIS IN BALB/C MICE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE MACROPHAGES; CL(2)MDP-LIPOSOMES; HERPES SIMPLEX VIRUS TYPE 1; CHORIORETINITIS; ANTI-CD11B MONOCLONAL ANTIBODY ID HERPES-SIMPLEX VIRUS; ENCAPSULATED DICHLOROMETHYLENE DIPHOSPHONATE; ANTERIOR-CHAMBER INOCULATION; MONOCLONAL-ANTIBODIES; SUICIDE TECHNIQUE; MECHANISMS; DEPLETION; CELLS; RAT; REPOPULATION AB Purpose. To examine the effects of modification of immune effector cells, including macrophages, in the pathogenesis of herpes simplex virus retinitis in BALB/c mice. Methods. Two intravitreal injections (2 mu l each) of anti-CD11b monoclonal antibody (mAb) [13 mu g/mu l] were administered to the contralateral eyes of 10 BALB/c mice on days 6 and 8 after HSV inoculation into the right anterior chamber (AC) with HSV-1. A control group consisted of mice injected with anti-HLA-DR mAb in the same fashion. Specific macrophage depletion was performed in an additional group of 12 BALB/c mice by intravenous (IV) injection of dichloromethylene diphosphonate (Cl(2)MDP)-liposomes 7 days before AC HSV-1 inoculation into the eye. Control group consisted of mice receiving IV PBS-liposomes. Mice were clinically observed for 14 days postinfection, and the incidence of chorioretinal disease was confirmed by histopathologic studies. Results. Intravitreal injections of anti-CD11b mAb produced a dramatic suppression of the contralateral retinal necrosis (2 of 10 mice) compared to 9 of 10 controls receiving an irrelevant antibody therapy (P < 0.05). Mice treated with IV Cl(2)MDP-liposomes also showed a significant inhibition of the development of contralateral chorioretinitis, with only 3 of 12 mice developing retinal disease compared to 9 of 12 mice from the control group (P < 0.05). FACS analysis performed on peripheral blood and spleen cells showed a significant depletion of Mac-1(+) cells of Cl(2)MDP-liposome-treated but not of PBS-liposome-treated mice (controls). Conclusion. Intravitreal anti-CD11b mAb therapy, a broadly directed depletion strategy against many effector cells (macrophages, granulocytes, natural killer cells, and even cytotoxic T-cells) was most efficient in suppressing the HSV-1 induced contralateral disease. A more Specific technique (IV Cl(2)MDP-liposome therapy) to deplete macrophages also produced a significant inhibition of HSV-1 induced contralateral chorioretinitis. These findings suggest that macrophages are important participants in the effector phase of the destructive inflammatory immune response induced by HSV-1 in the eye. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,HILLES IMMUNOL LAB,BOSTON,MA 02114. FREE UNIV AMSTERDAM,FAC MED,DEPT CELL BIOL,DIV HISTOL,AMSTERDAM,NETHERLANDS. OI Rodriguez-Garcia, Alejandro/0000-0002-1419-2109 FU NEI NIH HHS [EY06008] NR 39 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1994 VL 35 IS 7 BP 2990 EP 2998 PG 9 WC Ophthalmology SC Ophthalmology GA NR053 UT WOS:A1994NR05300012 PM 7911460 ER PT J AU ADAMS, MD POIRIER, VC HAMM, B WOLF, GL HANNA, G LASSER, EC FRIJA, G LIPTON, MJ BETTMANN, MA SPINAZZI, A SPECK KATZBERG, RW DAWSON, P SOVAK, M ALMEN, T GRABOWSKI, EF AF ADAMS, MD POIRIER, VC HAMM, B WOLF, GL HANNA, G LASSER, EC FRIJA, G LIPTON, MJ BETTMANN, MA SPINAZZI, A SPECK KATZBERG, RW DAWSON, P SOVAK, M ALMEN, T GRABOWSKI, EF TI PROCEEDINGS OF THE CONTRAST-MEDIA RESEARCH SYMPOSIUM - SAN-ANTONIO, TEXAS - OCTOBER 3-8, 1993 - DISCUSSION-3 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 UNIV CALIF DAVIS, MED CTR, DEPT RADIOL, SACRAMENTO, CA 95817 USA. FREE UNIV BERLIN, KLINIKUM CHARITE, DEPT RADIOL, D-10117 BERLIN, GERMANY. MASSACHUSETTS GEN HOSP E, CTR IMAGING & PHARMACEUT RES, BOSTON, MA USA. ALLIANCE PHARMACEUT CORP, SAN DIEGO, CA 92121 USA. UNIV CALIF SAN DIEGO, DEPT RADIOL 0632, LA JOLLA, CA 92093 USA. FAC MED NECKER ENFANTS MALAD, RECH IMAGERIE LAB, F-75015 PARIS, FRANCE. UNIV CHICAGO, DEPT RADIOL, CHICAGO, IL 60637 USA. DARTMOUTH HITCHCOCK MED CTR, DEPT RADIOL, DIV CARDIOVASC & INTERVENT RADIOL, LEBANON, NH 03756 USA. BRACCO IND CHIM SPA, DEPT MED, DIV R&D, MILAN, ITALY. UNIV CALIF DAVIS, MED CTR, DEPT RADIOL, SACRAMENTO, CA 95817 USA. HAMMERSMITH HOSP, ROYAL POSTGRAD MED SCH, DEPT RADIOL, LONDON W12 0NN, ENGLAND. UNIV CALIF SAN DIEGO, SCH MED, DEPT RADIOL, LA JOLLA, CA 92093 USA. BIOPHYS FDN, LA JOLLA, CA USA. MALMO GEN HOSP, DEPT RADIOL, S-21401 MALMO, SWEDEN. MASSACHUSETTS GEN HOSP, CARDIOVASC THROMBOSIS LAB, PEDIAT HEMATOL ONCOL UNIT, BOSTON, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S47 EP S49 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500017 ER PT J AU ALMEN, T LASSER, EC GRABOWSKI, EF RANGANATHAN, RS MORRIS, TW DAWSON, P FRANK, JA BETTMANN, MA COCHRAN, ST ANDREW, E GOLDSTEIN, HA AF ALMEN, T LASSER, EC GRABOWSKI, EF RANGANATHAN, RS MORRIS, TW DAWSON, P FRANK, JA BETTMANN, MA COCHRAN, ST ANDREW, E GOLDSTEIN, HA TI PROCEEDINGS OF THE CONTRAST-MEDIA RESEARCH SYMPOSIUM - SAN-ANTONIO, TEXAS - OCTOBER 3-8, 1993 - DISCUSSION-11 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 UNIV CALIF SAN DIEGO,DEPT RADIOL,LA JOLLA,CA 92093. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,PRINCETON,NJ 08543. HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT RADIOL,LONDON,ENGLAND. OD,OIR,DIAGNOST RADIOL RES LAB,BETHESDA,MD. DARTMOUTH COLL,HITCHCOCK MED CTR,DIV CARDIOVASC,LEBANON,NH. NYCOMED AS,N-0401 OSLO,NORWAY. UNIV CALIF LOS ANGELES,SCH MED,DEPT RADIOL SCI,LOS ANGELES,CA 90024. BERLEX LABS INC,WAYNE,NJ. RP ALMEN, T (reprint author), MALMO GEN HOSP,DEPT RADIOL,S-21401 MALMO,SWEDEN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S211 EP S213 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500070 ER PT J AU DAWSON, P FRANK, JA CAVAGNA, FM RUNGE, VM LAUFFER COROT, C NIENDORF, HP SPECK SOVAK, M WOLFE UNGER, E GOLMAN, K HARNISH, P GRABOWSKI, EF NUNN LIPTON, MJ FRITZZIEROTH, B WATSON, AD DEHAEN, C AF DAWSON, P FRANK, JA CAVAGNA, FM RUNGE, VM LAUFFER COROT, C NIENDORF, HP SPECK SOVAK, M WOLFE UNGER, E GOLMAN, K HARNISH, P GRABOWSKI, EF NUNN LIPTON, MJ FRITZZIEROTH, B WATSON, AD DEHAEN, C TI PROCEEDINGS OF THE CONTRAST-MEDIA RESEARCH SYMPOSIUM - SAN-ANTONIO, TEXAS - OCTOBER 3-8, 1993 - DISCUSSION-9 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 OD,OIR,DIAGNOST RADIOL RES LAB,BETHESDA,MD. BRACCO IND CHIM SPA,DIV RES & DEV,I-20134 MILAN,ITALY. UNIV KENTUCKY,CTR MAGNET RESONANCE IMAGING & SPECT,DEPT DIAGNOST RADIOL,LEXINGTON,KY. UNIV CHICAGO,DEPT RADIOL,CHICAGO,IL 60637. BIOMATECH,GCA GUERBET,F-38670 CHASSE SUR RHONE,FRANCE. SCHERING AG,CLIN RES & DEV DIAGNOST,D-13342 BERLIN,GERMANY. UNIV CALIF SAN DIEGO,SCH MED,DEPT RADIOL,LA JOLLA,CA 92093. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR IMAGING & PHARMACEUT RES,BOSTON,MA. UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT RADIOL,TUCSON,AZ 85724. LUND UNIV,MALMO GEN HOSP,DEPT EXPTL RES,S-21401 MALMO,SWEDEN. STERLING WINTHROP,DIV PHARMACEUT RES,COLLEGEVILLE,PA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NIHON SCHERING KK,RES DEPT,KYOTO,JAPAN. NYCOMED SALUTAR INC,SUNNYVALE,CA 94086. BRACCO IND CHIM SPA,DIV RES & DEV,MILAN,ITALY. RP DAWSON, P (reprint author), HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT RADIOL,LONDON W12 0NN,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S170 EP S173 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500056 ER PT J AU DEAN DEHAEN, C CAVAGAU WILSON, AJ BETTMANN, MA DUNCAN, JR LEE, FT MIYAZAWA, T WOLF, GL MORRIS, TW GRABOWSKI, EF NUNN RUBEN, DL LASSER, EC KORMANO, M SPECK HYAKAWA, K AF DEAN DEHAEN, C CAVAGAU WILSON, AJ BETTMANN, MA DUNCAN, JR LEE, FT MIYAZAWA, T WOLF, GL MORRIS, TW GRABOWSKI, EF NUNN RUBEN, DL LASSER, EC KORMANO, M SPECK HYAKAWA, K TI PROCEEDINGS OF THE CONTRAST-MEDIA RESEARCH SYMPOSIUM - SAN-ANTONIO, TEXAS - OCTOBER 3-8, 1993 - DISCUSSION-6 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 BRACCO IND CHIM SPA,DIV RES & DEV,MILAN,ITALY. FLINDERS UNIV S AUSTRALIA,FLINDERS MED CTR,DEPT RADIOL,BEDFORD PK,SA 5042,AUSTRALIA. DARTMOUTH HITCHCOCK MED CTR,DEPT RADIOL,DIV CARDIOVASC & INTERVENT RADIOL,LEBANON,NH 03756. WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. UNIV WISCONSIN,DEPT RADIOL,MADISON,WI 53706. UNIV WISCONSIN HOSP & CLIN,DEPT RADIOL,MADISON,WI. NIHON SCHERING KK,DEPT RES,KYOTO,JAPAN. MASSACHUSETTS GEN HOSP E,CTR IMAGING & PHARMACEUT RES,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CARDIOVASC THROMBOSIS LAB,ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV CALIF SAN DIEGO,DEPT RADIOL 0632,LA JOLLA,CA 92093. UNIV TURKU,DEPT DIAGNOST RADIOL,TURKU,FINLAND. KYOTO CITY HOSP,DEPT RADIOL,NAKAKYO KU,KYOTO 604,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S113 EP S115 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500038 ER PT J AU DEHAEN, C BENNESS, G VEXLER, VS CAVANGA, FM HIGGINS, CB MASUI, T BRASCH, RC GAZELLE, GS ROSATI, G ANDREW, E MUELLER NIENDORF, HP LANGE HARNISH, PP NUNNALLY DEAN, KI AF DEHAEN, C BENNESS, G VEXLER, VS CAVANGA, FM HIGGINS, CB MASUI, T BRASCH, RC GAZELLE, GS ROSATI, G ANDREW, E MUELLER NIENDORF, HP LANGE HARNISH, PP NUNNALLY DEAN, KI TI PROCEEDINGS OF THE CONTRAST-MEDIA RESEARCH SYMPOSIUM - SAN-ANTONIO, TEXAS - OCTOBER 3-8, 1993 - DISCUSSION-10 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 QUEEN ELIZABETH MED CTR,MRI UNIT,PERTH,WA,AUSTRALIA. UNIV CALIF SAN FRANCISCO,DEPT RADIOL,CONTRAST MEDIA LAB,SAN FRANCISCO,CA 94143. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR IMAGING & PHARMACEUT RES,BOSTON,MA. BRACCO IND CHIM SPA,DEPT MED,DIV RES & DEV,MILAN,ITALY. NYCOMED AS,N-0401 OSLO,NORWAY. SCHERING AG,CLIN RES & DEV DIAGNOST,W-1000 BERLIN,GERMANY. STERLING WINTHROP,DIV PHARMACEUT RES,COLLEGEVILLE,PA. RP DEHAEN, C (reprint author), BRACCO IND CHIM SPA,DIV RES & DEV,VIA E FOLLI 50,I-20134 MILAN,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S192 EP S194 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500063 ER PT J AU DESSER, TS SELTZER, SE LASSER, EC BRASCH, RC GRABOWSKI, EF ADZAMLI, K KOENIG, SH SMALL, WC WOLF, GL DEHAEN, C DAVIS, A SPECK WATSON, AD FELLMANN, JD AF DESSER, TS SELTZER, SE LASSER, EC BRASCH, RC GRABOWSKI, EF ADZAMLI, K KOENIG, SH SMALL, WC WOLF, GL DEHAEN, C DAVIS, A SPECK WATSON, AD FELLMANN, JD TI PROCEEDINGS OF THE CONTRAST-MEDIA RESEARCH SYMPOSIUM - SAN-ANTONIO, TEXAS - OCTOBER 3-8, 1993 - DISCUSSION-2 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. UNIV CALIF SAN DIEGO,DEPT RADIOL 0632,LA JOLLA,CA 92093. UNIV CALIF SAN FRANCISCO,DEPT RADIOL,CONTRAST MEDIA LAB,SAN FRANCISCO,CA 94143. MASSACHUSETTS GEN HOSP,CARDIOVASC THROMBOSIS LAB,PEDIAT HEMATOL ONCOL UNIT,BOSTON,MA 02114. MALLINCKRODT MED INC,DEPT RADIOL,ST LOUIS,MO 63134. RELAXOMETRY INC,MAHOPAC,NY 10541. EMORY UNIV,SCH MED,DEPT RADIOL,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP E,CTR IMAGING & PHARMACEUT RES,BOSTON,MA. BRACCO IND CHIM SPA,DIV RES & DEV,I-20134 MILAN,ITALY. UNIV MASSACHUSETTS,MED CTR,DEPT RADIOL,DIV RADIOL RES,WORCESTER,MA 01655. NYCOMED SALUTAR INC,SUNNYVALE,CA 94086. RP DESSER, TS (reprint author), STANFORD UNIV,SCH MED,DEPT RADIOL,CONTRAST MEDIA LAB,S-074,300 PASTEUR DR,STANFORD,CA 94305, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S27 EP S29 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500010 ER PT J AU GAZELLE, GS WOLF, GL BACON, ER MCINTIRE, GL COOPER, ER TONER, JL AF GAZELLE, GS WOLF, GL BACON, ER MCINTIRE, GL COOPER, ER TONER, JL TI NANOCRYSTALLINE COMPUTED-TOMOGRAPHY CONTRAST AGENTS FOR BLOOD-POOL AND LIVER-SPLEEN IMAGING SO INVESTIGATIVE RADIOLOGY LA English DT Article; Proceedings Paper CT 1993 Meeting of Contrast Media Research (CMR 93) CY OCT 03-08, 1993 CL SAN ANTONIO, TX SP BRACCO IND CHIM, MILAN, BRISTOL MYERS SQUIBB, PRINCETON, LAB GUERBET, PARIS, MALLINCKRODT MED, ST LOUIS, NYCOMED, OSLO, SCHERING, BERLIN, STERLING WINTHROP, COLLEGEVILLE, ADV MAGNET, CAMBRIDGE, ALLIANCE, SAN DIEGO, BERLEX, WAYNE, BRACCO RES, GENEVA, BYK GULDEN, KONSTANZ, COOK IMAGING, BLOOMINGTON, DAIICHI PHARM, TOKYO, IMARX, TUCSON, JUSTESA IMAGEN, MADRID, METASYN, CAMBRIDGE, MOLEC BIOSYST, SAN DIEGO, NIHON SCHERING, OSAKA, SALUTAR, SUNNYVALE DE LIVER; COMPUTED TOMOGRAPHY; CONTRAST AGENTS ID ARTERIAL PORTOGRAPHY; DELAYED CT C1 STERLING WINTHROP,DIV PHARMACEUT RES,COLLEGEVILLE,PA. RP GAZELLE, GS (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CTR IMAGING & PHARMACEUT RES,FRUIT ST,BOSTON,MA, USA. NR 10 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S286 EP S288 DI 10.1097/00004424-199406001-00098 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500098 PM 7928258 ER PT J AU GRABOWSKI, EF HEAD, C MICHAIL, HA JANG, IK GOLD, H BENOIT, SE MICHELSON, AD AF GRABOWSKI, EF HEAD, C MICHAIL, HA JANG, IK GOLD, H BENOIT, SE MICHELSON, AD TI EFFECTS OF CONTRAST-MEDIA ON PLATELET ACTIVATION USING FLOWING WHOLE-BLOOD AGGREGOMETRY AND FLOW-CYTOMETRY OF PLATELET MEMBRANE-GLYCOPROTEINS SO INVESTIGATIVE RADIOLOGY LA English DT Article; Proceedings Paper CT 1993 Meeting of Contrast Media Research (CMR 93) CY OCT 03-08, 1993 CL SAN ANTONIO, TX SP BRACCO IND CHIM, MILAN, BRISTOL MYERS SQUIBB, PRINCETON, LAB GUERBET, PARIS, MALLINCKRODT MED, ST LOUIS, NYCOMED, OSLO, SCHERING, BERLIN, STERLING WINTHROP, COLLEGEVILLE, ADV MAGNET, CAMBRIDGE, ALLIANCE, SAN DIEGO, BERLEX, WAYNE, BRACCO RES, GENEVA, BYK GULDEN, KONSTANZ, COOK IMAGING, BLOOMINGTON, DAIICHI PHARM, TOKYO, IMARX, TUCSON, JUSTESA IMAGEN, MADRID, METASYN, CAMBRIDGE, MOLEC BIOSYST, SAN DIEGO, NIHON SCHERING, OSAKA, SALUTAR, SUNNYVALE DE CONTRAST MEDIA; PLATELETS; AGGREGOMETRY; FLOW CYTOMETRY; SHEAR RATE ID CORONARY ANGIOPLASTY; AGGREGATION; INVITRO; INVIVO C1 HARVARD UNIV,SCH MED,BOSTON,MA. UNIV MASSACHUSETTS,SCH MED,WORCESTER,MA. RP GRABOWSKI, EF (reprint author), MASSACHUSETTS GEN HOSP,CARDIOVASC THROMBOSIS LAB,PEDIAT HEMATOL ONCOL UNIT,JACKSON 13,BOSTON,MA 02114, USA. NR 17 TC 0 Z9 0 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 JUN PY 1994 VL 29 SU 2 BP S198 EP S200 DI 10.1097/00004424-199406001-00065 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500065 PM 7928228 ER PT J AU TWEEDLE, M ADAMS, MD MATTREY, RF DUNCAN, JR NIENDORF NUNNALLY UNGER, E GRABOWSKI, EF KLAVENESS SCHNEIDER, M DEHAEN HOLTZ, E MOREAU SPECK KALLIO, T AF TWEEDLE, M ADAMS, MD MATTREY, RF DUNCAN, JR NIENDORF NUNNALLY UNGER, E GRABOWSKI, EF KLAVENESS SCHNEIDER, M DEHAEN HOLTZ, E MOREAU SPECK KALLIO, T TI PROCEEDINGS OF THE CONTRAST-MEDIA RESEARCH SYMPOSIUM - SAN-ANTONIO, TEXAS - OCTOBER 3-8, 1993 - DISCUSSION-8 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. UNIV CALIF SAN DIEGO,INST MAGNET RESONANCE,DEPT RADIOL,SAN DIEGO,CA 92103. WASHINGTON UNIV,SCH MED,EDWARD MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. SCHERING AG,CLIN RES & DEV DIAGNOST,D-13342 BERLIN,GERMANY. UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT RADIOL,TUCSON,AZ 85724. IMARX PHARMACEUT CORP,TUCSON,AZ. MASSACHUSETTS GEN HOSP,CARDIOVASC THROMBOSIS LAB,PEDIAT HEMATOL ONCOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BRACCO RES SA,CH-1227 CAROUGE,SWITZERLAND. BRACCO IND CHIM SPA,DIV RES & DEV,I-20134 MILAN,ITALY. NYCOMED IMAGING SA,RES & DEV,N-0401 OSLO,NORWAY. HOP NECKER ENFANTS MALAD,DEPT RADIOL,F-75015 PARIS,FRANCE. UNIV TURKU,DEPT DIAGNOST RADIOL,TURKU,FINLAND. RP TWEEDLE, M (reprint author), BRISTOL MYERS SQUIBB CO,PHARMACEUT RES INST,POB 4000,PRINCETON,NJ 08543, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S152 EP S153 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500050 ER PT J AU HARRIS, SE BONEWALD, LF HARRIS, MA SABATINI, M DALLAS, S FENG, JQ GHOSHCHOUDHURY, N WOZNEY, J MUNDY, GR AF HARRIS, SE BONEWALD, LF HARRIS, MA SABATINI, M DALLAS, S FENG, JQ GHOSHCHOUDHURY, N WOZNEY, J MUNDY, GR TI EFFECTS OF TRANSFORMING GROWTH-FACTOR-BETA ON BONE NODULE FORMATION AND EXPRESSION OF BONE MORPHOGENETIC PROTEIN-2, OSTEOCALCIN, OSTEOPONTIN, ALKALINE-PHOSPHATASE, AND TYPE-1 COLLAGEN MESSENGER-RNA IN LONG-TERM CULTURES OF FETAL-RAT CALVARIAL OSTEOBLASTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID CELL-PROLIFERATION; GENE-EXPRESSION; FORMED INVITRO; VITAMIN-D; STIMULATION; INHIBITION; INVIVO; MATRIX; REPLICATION; TGF-BETA-1 AB Transforming growth factor beta (TGF-beta) is one of the most abundant of the known growth regulatory factors stored within the bone matrix. When bone is resorbed, TGF-beta is released in an active form and is a powerful bone growth stimulant. When injected into the subcutaneous tissue over the calvarial surface of rodents, it rapidly causes proliferation of the periosteal layer and accumulation of new woven bone. In this report, we describe the effects of TGF-beta(1) on first subcultures of fetal rat osteoblasts obtained from calvarial bones and cultured from confluence with ascorbic acid and beta-glycerophosphate. Under these conditions, nodules with characteristics of normal bone appear by day 8. Similar to experiments described by Antosz et al., TGF-beta added to confluent cultures inhibited the formation of bone nodules. Both the number and total area of the nodules were quantitated and shown to be completely inhibited by 2 ng/ml of TGF-beta(1). TGF-beta also impaired the expression of genes associated with bone formation, including type I collagen, alkaline phosphatase, osteopontin, and osteocalcin. TGF-beta also inhibited the expression of mRNA for the bone morphogenetic protein 2 (BMP-2). These results, showing suppression of markers representative of osteoblast differentiation, suggest that the effects of TGF-beta to stimulate bone formation in vivo are not likely a result of effects on differentiated mineralizing osteoblasts but, as suggested by previous studies, more likely are caused by effects on osteoblast precursors. These results also suggest that endogenous BMP-2 expression in fetal rat calvaria cells is important for bone cell differentiation. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,DEPT VET AFFAIRS,SAN ANTONIO,TX. INST RECH SERVIER,F-92150 SURESNES,FRANCE. GENET INST INC,CAMBRIDGE,MA 02140. FU NIAMS NIH HHS [AR39529]; NIDCR NIH HHS [DE08569] NR 33 TC 244 Z9 250 U1 1 U2 13 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1994 VL 9 IS 6 BP 855 EP 863 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NN314 UT WOS:A1994NN31400010 PM 8079661 ER PT J AU LO, SH JANMEY, PA HARTWIG, JH CHEN, LB AF LO, SH JANMEY, PA HARTWIG, JH CHEN, LB TI INTERACTIONS OF TENSIN WITH ACTIN AND IDENTIFICATION OF ITS 3 DISTINCT ACTIN-BINDING DOMAINS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID END-BOUND INSERTIN; FOCAL ADHESIONS; ALPHA-ACTININ; BARBED ENDS; MICROFILAMENT BUNDLES; ADHERENS JUNCTIONS; CHICKEN GIZZARD; CELL-ADHESION; SMOOTH-MUSCLE; SH3 DOMAINS AB Tensin, a 200-kD phosphoprotein of focal contacts, contains sequence homologies to Src (SH2 domain), and several actin-binding proteins. These features suggest that tensin may link the cell membrane to the cytoskeleton and respond directly to tyrosine kinase signalling pathways. Here we identify three distinct actin-binding domains within tensin. Recombinant tensin purified after overexpression by a baculovirus system binds to actin filaments with K-d = 0.1 mu M, cross-links actin filaments at a molar ratio of 1:10 (tensin/actin), and retards actin assembly by barbed end capping with K-d = 20 nM. Tensin fragments were constructed and expressed as fusion proteins to map domains having these activities. Three regions from tensin interact with actin: two regions composed of amino acids 1 to 263 and 263 to 463, cosediment with F-actin but do not alter the kinetics of actin assembly; a region composed of amino acids 888-989, with sequence homology to insertin, retards actin polymerization. A claw-shaped tensin dimer would have six potential actin-binding sites and could embrace the ends of two actin filaments at focal contacts. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 47874]; NIDDK NIH HHS [DK 38452]; NIGMS NIH HHS [GM 38318] NR 57 TC 112 Z9 112 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN PY 1994 VL 125 IS 5 BP 1067 EP 1075 DI 10.1083/jcb.125.5.1067 PG 9 WC Cell Biology SC Cell Biology GA NN473 UT WOS:A1994NN47300011 PM 8195290 ER PT J AU SANANTONIO, JD LANDER, AD KARNOVSKY, MJ SLAYTER, HS AF SANANTONIO, JD LANDER, AD KARNOVSKY, MJ SLAYTER, HS TI MAPPING THE HEPARIN-BINDING SITES ON TYPE-I COLLAGEN MONOMERS AND FIBRILS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; LENGTH CDNA CLONE; SULFATE PROTEOGLYCANS; ANTI-THROMBIN; TUMOR CELLS; PROCOLLAGEN; SEQUENCE; GLYCOSAMINOGLYCANS; IDENTIFICATION; ADHESION AB The glycosaminoglycan chains of cell surface heparan sulfate proteoglycans are believed to regulate cell adhesion, proliferation, and extracellular matrix assembly, through their interactions with heparin-binding proteins (for review see Ruoslahti, E. 1988. Annu. Rev Cell Biol. 4:229-255; and Bernfield, M., R. Kokenyesi, M. Kato, M. T. Hinkes, J. Spring, R. L. Gallo, and E. J. Lose. 1992. Annu. Rev. Cell Biol. 8:365-393). Heparin-binding sites on many extracellular matrix proteins have been described; however, the heparin-binding site on type I collagen, a ubiquitous heparin-binding protein of the extracellular matrix, remains undescribed. Here we used heparin, a structural and functional analogue of heparan sulfate, as a probe to study the nature of the heparan sulfate proteoglycan-binding site on type I collagen. We used affinity coelectrophoresis to study the binding of heparin to various forms of type I collagen, and electron microscopy to visualize the site(s) of interaction of heparin with type I collagen monomers and fibrils. Using affinity coelectrophoresis it was found that heparin has similar affinities for both procollagen and collagen fibrils (K-d's similar to 60-80 nM), suggesting that functionally similar heparin-binding sites exist in type I collagen independent of its aggregation state. Complexes of heparin-albumin-gold particles and procollagen were visualized by rotary shadowing and electron microscopy, and a preferred site of heparin binding was observed near the NH2 terminus of procollagen. Native or reconstituted type I collagen fibrils showed one region of significant heparin-gold binding within each 67-nm period, present near the division between the overlap and gap zones, within the ''a'' bands region. According to an accepted model of collagen fibril structure, our data are consistent with the presence of a single preferred heparin-binding site near the NH,, terminus of the collagen monomer. Correlating these data with known type I collagen sequences, we suggest that the heparin-binding site in type I collagen may consist of a highly basic triple helical domain, including several amino acids known sometimes to function as disaccharide acceptor sites. We propose that the heparin-binding site of type I collagen may play a key role in cell adhesion and migration within connective tissues, or in the cell-directed assembly or restructuring of the collagenous extracellular matrix. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, MOLEC STRUCT LAB, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. MIT, DEPT BRAIN & COGNIT SCI, CAMBRIDGE, MA 02139 USA. MIT, DEPT BIOL, CAMBRIDGE, MA 02139 USA. HARVARD UNIV, SCH MED, DEPT CELLULAR & MOLEC PHYSIOL, BOSTON, MA 02115 USA. RI Lander, Arthur/C-9008-2011 FU NHLBI NIH HHS [HL 17747, HL 33014] NR 56 TC 75 Z9 75 U1 1 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD JUN PY 1994 VL 125 IS 5 BP 1179 EP 1188 DI 10.1083/jcb.125.5.1179 PG 10 WC Cell Biology SC Cell Biology GA NN473 UT WOS:A1994NN47300021 PM 8195298 ER PT J AU LUSCINSKAS, FW KANSAS, GS DING, H PIZCUETA, P SCHLEIFFENBAUM, BE TEDDER, TF GIMBRONE, MA AF LUSCINSKAS, FW KANSAS, GS DING, H PIZCUETA, P SCHLEIFFENBAUM, BE TEDDER, TF GIMBRONE, MA TI MONOCYTE ROLLING, ARREST AND SPREADING ON IL-4-ACTIVATED VASCULAR ENDOTHELIUM UNDER FLOW IS MEDIATED VIA SEQUENTIAL ACTION OF L-SELECTIN, BETA(1)-INTEGRINS, AND BETA(2)-INTEGRINS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; TUMOR-NECROSIS-FACTOR; CELL-ADHESION; HUMAN-NEUTROPHILS; HOMING RECEPTOR; TRANSENDOTHELIAL MIGRATION; CHEMOTACTIC FACTORS; MESENTERIC VENULES; SHEAR-STRESS; T-CELLS AB Leukocyte interactions with vascular endothelium at sites of inflammation can be dynamically regulated by activation-dependent adhesion molecules. Current models, primarily based on studies with polymorphonuclear leukocytes, suggest the involvement of multiple members of the selectin, integrin, and immunoglobulin gene families, sequentially, in the process of initial attachment (rolling), stable adhesion (arrest), spreading and ultimate diapedesis. In the current study, IL-4-activated human umbilical vein endothelium, which selectively expresses VCAM-1 and an L-selectin ligand but not E-selectin, and appropriate function blocking monoclonal antibodies, were used to study monocyte-endothelial interactions in an in vitro model that mimics microcirculatory flow conditions. In this system, L-selectin mediates monocyte rolling and also facilitates alpha(4) beta(1)-integrin-dependent arrest, whereas beta(2)-integrins are required for spreading of firmly attached monocytes on the endothelial cell surface but not their arrest. These findings provide the first in vitro evidence for human monocyte rolling on cytokine-activated endothelium, and suggest a sequential requirement for both beta(1)- and beta(2)-integrin-dependent adhesive mechanisms in monocyte-endothelial interactions. C1 HARVARD UNIV,DANA FARBER CANC INST,SCH MED,DEPT PATHOL,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,DANA FARBER CANC INST,SCH MED,DEPT MED,BOSTON,MA 02115. DUKE UNIV,MED CTR,DEPT IMMUNOL,DURHAM,NC 27710. RP LUSCINSKAS, FW (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV VASC RES,221 LONGWOOD AVE,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-36167]; NHLBI NIH HHS [HL-47646, P01-HL-36028] NR 67 TC 334 Z9 337 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN PY 1994 VL 125 IS 6 BP 1417 EP 1427 DI 10.1083/jcb.125.6.1417 PG 11 WC Cell Biology SC Cell Biology GA NT420 UT WOS:A1994NT42000019 PM 7515891 ER PT J AU CRYNS, VL RUBIO, MP THOR, AD LOUIS, DN ARNOLD, A AF CRYNS, VL RUBIO, MP THOR, AD LOUIS, DN ARNOLD, A TI P53 ABNORMALITIES IN HUMAN PARATHYROID CARCINOMA SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POLYMERASE CHAIN-REACTION; STRAND CONFORMATION POLYMORPHISM; ENDOCRINE NEOPLASIA TYPE-1; TUMOR SUPPRESSOR GENE; LUNG-CANCER; CELL-CYCLE; PROTEIN ALTERATIONS; CANDIDATE ONCOGENE; HUMAN ASTROCYTOMAS; CHROMOSOME 11Q13 AB Two cell cycle regulators have been implicated in the pathogenesis of parathyroid neoplasms: rearrangement/overexpression of the PRAD1/cyclin D1 gene in parathyroid adenomas and inactivation of the retinoblastoma tumor suppressor gene in parathyroid carcinomas. We examined parathyroid tumors for evidence of molecular genetic abnormalities in another cell cycle regulator, the p53 tumor suppressor gene. Allelic loss of the p53 gene was observed in parathyroid carcinomas from 2 of 6 genetically informative patients. Moreover, 2 of 9 patients' parathyroid carcinomas had nuclear p53 protein detectable by immunohistochemical analysis, a finding that often reflects mutational stabilization of the p53 protein. Of these two p53-immunopositive carcinomas, 1 had p53 allelic loss and 1 was genetically uninformative. In contrast, none of 20 informative parathyroid adenomas exhibited p53 allelic loss; 1 of 19 adenomas had a focal region of nuclear p53 protein staining. Single strand conformation polymorphism analysis of exons 5-9 of the p53 gene did not reveal mutations in any parathyroid neoplasm, suggesting that such mutations in parathyroid tumors may lie outside of these conserved regions. The finding of both p53 allelic loss and abnormal p53 protein expression in parathyroid carcinomas implicates p53 in the pathogenesis of a subset of these tumors. C1 MASSACHUSETTS GEN HOSP, ENDOCRINE ONCOL LAB, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, MOLEC NEUROONCOL LAB, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, NEUROSURG SERV, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RI Rubio, Mari-Paz/K-4364-2014 OI Rubio, Mari-Paz/0000-0003-3963-5903 FU NCI NIH HHS [1F32-CA-0938101, 1K08-CA-01752-01A1]; NIDDK NIH HHS [5T32-DK-0702817] NR 57 TC 78 Z9 79 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 JUN PY 1994 VL 78 IS 6 BP 1320 EP 1324 DI 10.1210/jc.78.6.1320 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NQ265 UT WOS:A1994NQ26500009 PM 8200932 ER PT J AU ALEXANDER, JM KLIBANSKI, A AF ALEXANDER, JM KLIBANSKI, A TI GONADOTROPIN-RELEASING-HORMONE RECEPTOR MESSENGER-RNA EXPRESSION BY HUMAN PITUITARY-TUMORS IN-VITRO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GONADOTROPIN; ADENOMA; PATHOGENESIS; PULSATILE; PERIFUSION ID FOLLICLE-STIMULATING-HORMONE; ALPHA-SUBUNIT SECRETION; RIBONUCLEIC-ACID LEVELS; LUTEINIZING-HORMONE; CUSHINGS-DISEASE; ANTERIOR-PITUITARY; MOLECULAR-CLONING; ADENOMAS INVIVO; CLONAL ORIGIN; BETA-SUBUNIT AB An important question in the pathogenesis and regulation of human gonadotroph adenomas is whether heterogeneous gonadotropin responses to gonadotropin-releasing hormone(GnRH) are due to dysregulation of GnRH receptor biosynthesis and/or cell-signaling pathways. We investigated gonadotropin responsiveness to pulsatile GnRH in 13 gonadotroph adenomas. All tumors had evidence of follicle-stimulating hormone (FSH) beta and alpha subunit biosynthesis using reverse transcriptase/polymerase chain reaction (RTPCR) techniques. Four tumors significantly increased gonadotropin and/or free subunit secretion during pulsatile 10(-8) M GnRH administration. The GnRH antagonist Antide (10(-6) to 10(-8) M) blocked secretory increases in all GnRH-responsive tumors. Gonadotropin and/or free subunit secretion increased after 60 mM KCl, confirming that GnRH nonresponsiveness was not due to intracellular gonadotropin depletion. We hypothesized that GnRH nonresponsiveness in these tumors may be due to GnRH receptor (GnRH-Rc) biosynthetic defects. RTPCR analyses detected GnRH-Rc transcripts only in responsive tumors and normal human pituitary. This is the first demonstration of a cell-surface receptor biosynthetic defect in human pituitary tumors. We conclude(a) one third of gonadotroph tumors respond to pulsatile GnRH in vitro, (b) GnRH-Rc mRNA is detected in human gonadotroph adenomas and predicts GnRH responsiveness, and (c) GnRH-Rc biosynthetic defects may underlie GnRH nonresponsiveness in gonadotroph tumors. C1 MASSACHUSETTS GEN HOSP,NEUROENDOCRINE UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NICHD NIH HHS [P30HD28138]; NIDDK NIH HHS [DK-40947] NR 40 TC 25 Z9 25 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 JUN PY 1994 VL 93 IS 6 BP 2332 EP 2339 DI 10.1172/JCI117238 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NP577 UT WOS:A1994NP57700008 PM 8200967 ER PT J AU PUGLIESE, A BUGAWAN, T MOROMISATO, R AWDEH, ZL ALPER, CA JACKSON, RA ERLICH, HA EISENBARTH, GS AF PUGLIESE, A BUGAWAN, T MOROMISATO, R AWDEH, ZL ALPER, CA JACKSON, RA ERLICH, HA EISENBARTH, GS TI 2 SUBSETS OF HLA-DQA1 ALLELES MARK PHENOTYPIC VARIATION IN LEVELS OF INSULIN AUTOANTIBODIES IN FIRST DEGREE RELATIVES AT RISK FOR INSULIN-DEPENDENT DIABETES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE AUTOIMMUNITY; DIABETES MELLITUS, INSULIN-DEPENDENT; INSULIN AUTOANTIBODIES; HLA CLASS II ANTIGENS; HLA-DQA1 ANTIGENS ID ISLET CELL ANTIBODIES; SUSCEPTIBILITY; MELLITUS; AUTOIMMUNITY; ASSOCIATION; RESISTANCE; ASSAY; LOCI AB Levels of insulin autoantibodies (IAA) vary among different first degree relatives of insulin-dependent diabetes mellitus patients, suggesting genetic regulation. We previously reported elevated IAA among DR l-positive at risk relatives. In this study, 72/82 at risk relatives were IAA positive, of whom 75% (54/72) carried DR4 versus 20% (2/10) of IAA-negative relatives (P = 0.0004). However, 69% (18/26) of DR4-negative relatives were IAA positive. Since DR4 did not account for all IAA positivity, we analyzed DQA1 and DQB1 alleles. Homozygosity for DQA1 alleles deriving from the evolutionary lineage 4 (*0401, *0501, *0601) was associated with low IAA levels, while lineage 1-3 alleles (*0101, *0102, *0103, *0201, *0301) correlated with higher levels. Most (93%, 65/70) relatives with lineage 1-3 alleles were IAA positive (mean = 360+/-63 SERI nU/ml). Only 7/12 relatives homozygous for lineage 4 alleles were IAA-positive, with lower levels than relatives with Lineage 1-3 alleles (mean = 55+/-15 SEM nU/ml, P < 0.0001; 7/12 vs 65/70, P = 0.004). The amino acid sequences of lineage 1-3 alleles uniquely share glutamic acid(E)and phenylalanine(F) at positions 40 and 51 (EF alleles). Lineage 4 alleles have glycine (G) and leucine (L) at those positions (GL alleles). 90% (65/72) of IAA-positive relatives had an EF allele, while only 75% (54/72) had DR4 (P = 0.01). Homozygosity for GL alleles (often DQA1 *0501 on DR3 haplotypes) correlated with little or no humoral response to insulin. Thus, HLA-DQB1 GL alleles, or other genes on haplotypes (e.g., DR3) that carry these DQA1 alleles, may confer recessive low responsiveness to insulin. C1 UNIV COLORADO,HLTH SCI CTR,BARBARA DAVIS CTR CHILDHOOD DIABET,DENVER,CO 80262. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. ROCHE MOLEC SYST,DEPT HUMAN GENET,ALAMEDA,CA 94501. FU NIA NIH HHS [R01-AG-07988]; NIDDK NIH HHS [R01-DK-47477, R029-DK-42177] NR 22 TC 36 Z9 40 U1 0 U2 1 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 JUN PY 1994 VL 93 IS 6 BP 2447 EP 2452 DI 10.1172/JCI117253 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NP577 UT WOS:A1994NP57700023 PM 8200980 ER PT J AU LIANG, Y BONNERWEIR, S WU, YJ BERDANIER, CD BERNER, DK EFRAT, S MATSCHINSKY, FM AF LIANG, Y BONNERWEIR, S WU, YJ BERDANIER, CD BERNER, DK EFRAT, S MATSCHINSKY, FM TI IN-SITU GLUCOSE-UPTAKE AND GLUCOKINASE ACTIVITY OF PANCREATIC-ISLETS IN DIABETIC AND OBESE RODENTS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE DIABETIC ANIMAL; GLUCOKINASE; GLUT2; INSULIN RELEASE; PANCREATIC ISLET ID BETA-CELLS; INSULIN-SECRETION; PLASMA-MEMBRANE; TRANSGENIC MICE; G-PROTEINS; BHE RAT; MELLITUS; TRANSPORTER; EXPRESSION; LANGERHANS AB The present study evaluated the involvement of glucose transport and phosphorylation in glucose-stimulated insulin release from pancreatic islets. Using quantitative histochemical techniques, we investigated basal islet glucose content, islet glucose uptake in situ during acute extreme experimental hyperglycemia, and islet glucokinase activity in several animal models of diabetes and obesity. The basal islet glucose content in anaesthetized diabetic or obese rodents was either the same or higher than that in their relevant controls. The rate of glucose uptake of islet tissue in these animals after an i.v. glucose injection was different. The db(+)/db(+) mouse and the obese Zucker rat exhibited significantly reduced islet glucose uptake rates. RIP-cHras transgenic mice, BHE/cdb rats and partially pancreatectomized rats showed normal islet glucose uptake rates. The activity of islet glucokinase was increased to a different degree related to the blood glucose level. All five animal models of diabetes or obesity exhibited either a delay or a reduction of insulin release in response to supra maximal glucose stimulation. Our results indicate that the impairment of glucose-induced insulin release in diabetes is not consistently associated with a reduction of islet glucose uptake nor a change of glucokinase activity. C1 UNIV PENN,CTR DIABET RES,PHILADELPHIA,PA 19104. UNIV PENN,DEPT BIOCHEM & BIOPHYS,PHILADELPHIA,PA 19104. JOSLIN DIABET CTR,BOSTON,MA 02215. UNIV GEORGIA,DEPT FOOD & NUTR,ATHENS,GA 30602. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MOLEC PHARMACOL,BRONX,NY 10461. FU NIDDK NIH HHS [DK-22122, DK-19525, DK-35449] NR 42 TC 39 Z9 39 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1994 VL 93 IS 6 BP 2473 EP 2481 DI 10.1172/JCI117256 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NP577 UT WOS:A1994NP57700026 PM 8200983 ER PT J AU TSUTSUI, H SPINALE, FG NAGATSU, M SCHMID, PG ISHIHARA, K DEFREYTE, G COOPER, G CARABELLO, BA AF TSUTSUI, H SPINALE, FG NAGATSU, M SCHMID, PG ISHIHARA, K DEFREYTE, G COOPER, G CARABELLO, BA TI EFFECTS OF CHRONIC BETA-ADRENERGIC-BLOCKADE ON THE LEFT-VENTRICULAR AND CARDIOCYTE ABNORMALITIES OF CHRONIC CANINE MITRAL REGURGITATION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE MITRAL VALVE INSUFFICIENCY; ADRENERGIC BETA RECEPTOR BLOCKADERS; VENTRICULAR FUNCTION; LEFT HEART FAILURE; CONGESTIVE HYPERTROPHY ID TACHYCARDIA-INDUCED CARDIOMYOPATHY; IDIOPATHIC DILATED CARDIOMYOPATHY; EXPERIMENTAL VOLUME OVERLOAD; CONGESTIVE-HEART-FAILURE; SUPRAVENTRICULAR TACHYCARDIA; CONTRACTILE DYSFUNCTION; RECEPTOR DENSITY; MYOCARDIAL-CELLS; MYOCYTE SIZE; WALL STRESS AB The mechanism by which beta blockade improves left ventricular dysfunction in various cardiomyopathies has been ascribed to improved contractile function of the myocardium or to improved beta-adrenergic responsiveness. In this study we tested two hypotheses: (a) that chronic beta blockade would improve the left ventricular dysfunction which develops in mitral regurgitation, and (b) that an important mechanism of this effect would be improved innate contractile function of the myocardium. Two groups of six dogs with chronic severe mitral regurgitation were studied. After 3 mo both groups had developed similar and significant left ventricular dysfunction. One group was then gradually beta-blocked while the second group continued to be observed without further intervention. In the group that remained unblocked, contractile function remained depressed. However, in the group that received chronic beta blockade, contractile function improved substantially. The contractility of cardiocytes isolated from the unblocked hearts and then studied in the absence of beta receptor stimulation was extremely depressed. However, contractility of cardiocytes isolated from the beta-blocked ventricles was virtually normal. Consistent with these data, myofibrillar density was much higher, 55 +/- 4% in the beta-blocked group vs. 39 +/- 2% (P < 0.01) in the unblocked group; thus, there were more contractile elements to generate force in the beta-blocked group. We conclude that chronic beta blockade improves left ventricular function in chronic experimental mitral regurgitation. This improvement was associated with an improvement in the innate contractile function of isolated cardiocytes, which in turn is associated with an increase in the number of contractile elements. C1 MED UNIV S CAROLINA,GAZES CARDIAC RES INST,DEPT MED,DIV CARDIOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT SURG,DIV CARDIOTHORAC,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29403. UNIV IOWA,VET AFFAIRS MED CTR,DEPT INTERNAL MED,IOWA CITY,IA 52246. RI Tsutsui, Hiroyuki/A-4070-2012 FU NHLBI NIH HHS [NHLBI R01 HL-38185] NR 64 TC 131 Z9 132 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1994 VL 93 IS 6 BP 2639 EP 2648 DI 10.1172/JCI117277 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NP577 UT WOS:A1994NP57700047 PM 7911128 ER PT J AU NG, LL DAVIES, JE SICZKOWSKI, M SWEENEY, FP QUINN, PA KROLEWSKI, B KROLEWSKI, AS AF NG, LL DAVIES, JE SICZKOWSKI, M SWEENEY, FP QUINN, PA KROLEWSKI, B KROLEWSKI, AS TI ABNORMAL NA+/H+ ANTIPORTER PHENOTYPE AND TURNOVER OF IMMORTALIZED LYMPHOBLASTS FROM TYPE-1 DIABETIC-PATIENTS WITH NEPHROPATHY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE DIABETIC NEPHROPATHY; PH REGULATION; NA+/H+ ANTIPORT; TURNOVER NUMBER; PROTEIN BLOTTING ID SODIUM-PROTON EXCHANGE; EPSTEIN-BARR VIRUS; ESSENTIAL-HYPERTENSION; INTRACELLULAR PH; PLASMA-MEMBRANES; H+ EXCHANGER; INSULIN; CELLS; MELLITUS; PHOSPHORYLATION AB Cellular Na+/H+ eschanger (NHE) activity is elevated in type 1 diabetic patients with nephropathy and patients with essential hypertension. The characteristics of this NHE phenotype in hypertension (raised V-max and a lowered Hill coefficient) are preserved in Epstein-Barr virus-transformed lymphoblasts from hypertensive patients. In this study, we have determined NHE kinetics in cultured lymphoblasts from diabetic patients with and without nephropathy, with nondiabetic controls, using fluorometry with the pH indicator 2,7' bis-(carboxyethyl)-5,6-carboxyfluorescein and estimation of NHE isoform 1 (NHE-1) density with specific polyclonal antibodies. The V-max of NHE was elevated significantly, and the Hill coefficient for internal H+ binding was lowered in cells from patients with diabetic nephropathy compared with both normal controls and normoalbuminuric diabetic patients. NHE-1 density as measured by Western blotting was similar in all groups. The turnover number of NHE-1 was thus elevated in cells from nephropathy patients. This phenotype in cells from diabetic nephropathy patients resembles that in essential hypertension and suggests that such patients may have a predisposition to hypertension. Moreover, as these changes persist in cultured lymphoblasts in vitro, these cells should provide a cell culture model to further define the basic mechanisms leading to NHE activation in diabetic nephropathy. C1 LEICESTER ROYAL INFIRM, DEPT MED & THERAPEUT, LEICESTER LE2 7LX, ENGLAND. HARVARD UNIV, SCH PUBL HLTH, DEPT CANC BIOL, BOSTON, MA 02215 USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK-36836, DK-41526]; Wellcome Trust NR 33 TC 75 Z9 75 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 1994 VL 93 IS 6 BP 2750 EP 2757 DI 10.1172/JCI117291 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NP577 UT WOS:A1994NP57700061 PM 8201013 ER PT J AU GHEESLING, LL CARLONE, GM PAIS, LB HOLDER, PF MASLANKA, SE PLIKAYTIS, BD ACHTMAN, M DENSEN, P FRASCH, CE KAYHTY, K MAYS, JP NENCIONI, L PEETERS, C PHIPPS, DC POOLMAN, JT ROSENQVIST, E SIBER, GR THIESEN, B TAI, J THOMPSON, CM VELLA, PP WENGER, JD AF GHEESLING, LL CARLONE, GM PAIS, LB HOLDER, PF MASLANKA, SE PLIKAYTIS, BD ACHTMAN, M DENSEN, P FRASCH, CE KAYHTY, K MAYS, JP NENCIONI, L PEETERS, C PHIPPS, DC POOLMAN, JT ROSENQVIST, E SIBER, GR THIESEN, B TAI, J THOMPSON, CM VELLA, PP WENGER, JD TI MULTICENTER COMPARISON OF NEISSERIA-MENINGITIDIS SEROGROUP-C ANTI-CAPSULAR POLYSACCHARIDE ANTIBODY-LEVELS MEASURED BY A STANDARDIZED ENZYME-LINKED-IMMUNOSORBENT-ASSAY SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFLUENZAE TYPE-B; RADIOANTIGEN BINDING ASSAY; GROUP-A; MENINGOCOCCAL DISEASE; ELISA; VACCINES; CHILDREN; RADIOIMMUNOASSAY; IMMUNIZATION; QUANTITATION AB A standardized enzyme-linked immunosorbent assay (ELISA) was used by 11 laboratories to measure levels of total serum antibody to Neisseria meningitidis serogroup C capsular polysaccharide in 16 unpaired pre- and postvaccination serum samples. Twelve serum samples were from adults, and four were from children aged 2, 3, 5, and 9. The between-laboratory coefficient of variation for pre- and postvaccination sera ranged from 16 to 59% and 11 to 21%, respectively. The average percent difference (absolute value) from the between laboratory means for all prevaccination sera measured by each laboratory was 24%, whereas the average percent difference was 13% for all postvaccination sera. A postvaccination quality control serum was diluted three times to give optical densities on the high, middle, and low portions of the standard reference curve. The three dilutions were assayed by the II laboratories a total of 241 times and yielded an overall coefficient of variation of 20%. Antibody-binding inhibition curves showed that the standardized ELISA was specific for N. meningitidis serogroup C capsular polysaccharide antibody. Fifty percent inhibition of seven serum samples was obtained after reaction with an average concentration of 0.9 mu g of meningococcal serogroup C polysaccharide per mi; an average of 93% inhibition was obtained with 50 pg of polysaccharide per mt The acceptance and use of this standardized ELISA will reduce between-laboratory assay variability and ensure a more accurate and reproducible assessment of immunogenicity for vaccines under development. C1 CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,CHILDHOOD & RESP DIS BRANCH,ATLANTA,GA 30333. CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,BIOSTAT & INFORMAT MANAGEMENT BRANCH,ATLANTA,GA 30333. MAX PLANCK INST MOLEC GENET,W-1000 BERLIN,GERMANY. UNIV IOWA,IOWA CITY,IA 52242. US FDA,BETHESDA,MD 20892. NATL PUBL HLTH INST,HELSINKI,FINLAND. CONNAUGHT LABS INC,SWIFTWATER,PA 18370. BIOCINE SCLAVO SPA,SIENA,ITALY. NATL INST PUBL HLTH & ENVIRONM PROTECT,3720 BA BILTHOVEN,NETHERLANDS. LEDERLE PRAXIS BIOL INC,W HENRIETTA,NY 14586. NATL INST PUBL HLTH,OSLO,NORWAY. DANA FARBER CANC INST,BOSTON,MA 02115. AMERICAN VACCINE CORP,AMVAX,BELTSVILLE,MD 20705. MERCK SHARP & DOHME LTD,RES LABS,W POINT,PA 19484. NR 32 TC 138 Z9 143 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 JUN PY 1994 VL 32 IS 6 BP 1475 EP 1482 PG 8 WC Microbiology SC Microbiology GA NL918 UT WOS:A1994NL91800011 PM 8077392 ER PT J AU MAZZULLI, T DOVEIKIS, SA HIRSCH, MS AF MAZZULLI, T DOVEIKIS, SA HIRSCH, MS TI COMPARISON OF CYTOMEGALOVIRUS ANTIGENEMIA ASSAY WITH SHELL VIAL-INDIRECT IMMUNOFLUORESCENCE ASSAY FOR RAPID DETECTION OF CYTOMEGALOVIRUS IN BLOOD - REPLY SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter ID VIRUS ISOLATION; CELL-CULTURES; RECIPIENTS; LEUKOCYTES; SPECIMENS; VIREMIA RP MAZZULLI, T (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,INFECT DIS UNIT,BOSTON,MA 02114, USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1994 VL 32 IS 6 BP 1619 EP 1620 PG 2 WC Microbiology SC Microbiology GA NL918 UT WOS:A1994NL91800045 ER PT J AU LOEHRER, PJ KIM, K AISNER, SC LIVINGSTON, R EINHORN, LH JOHNSON, D BLUM, R AF LOEHRER, PJ KIM, K AISNER, SC LIVINGSTON, R EINHORN, LH JOHNSON, D BLUM, R TI CISPLATIN PLUS DOXORUBICIN PLUS CYCLOPHOSPHAMIDE IN METASTATIC OR RECURRENT THYMOMA - FINAL RESULTS OF AN INTERGROUP TRIAL SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INVASIVE THYMOMA; MALIGNANT THYMOMA; CHEMOTHERAPY; THERAPY; EXPERIENCE C1 DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. UNIV WASHINGTON,DEPT RADIAT ONCOL,SEATTLE,WA. VANDERBILT UNIV,SCH MED,DIV MED ONCOL,NASHVILLE,TN. NYU,CTR MED,DIV MED ONCOL,NEW YORK,NY. RP LOEHRER, PJ (reprint author), INDIANA UNIV,MED CTR,DEPT MED,550 N UNIV BLVD,INDIANAPOLIS,IN 46202, USA. FU NCI NIH HHS [2 R 35 CA 39844-07, CA 21115]; NCRR NIH HHS [MO 1 RR 00 750-06] NR 25 TC 152 Z9 155 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 JUN PY 1994 VL 12 IS 6 BP 1164 EP 1168 PG 5 WC Oncology SC Oncology GA NP956 UT WOS:A1994NP95600011 PM 8201378 ER PT J AU ROSENBAUM, JF BIEDERMAN, J POLLOCK, RA HIRSHFELD, DR AF ROSENBAUM, JF BIEDERMAN, J POLLOCK, RA HIRSHFELD, DR TI THE ETIOLOGY OF SOCIAL PHOBIA SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Social Phobia: A Comprehensive Approach to Etiology, Diagnosis, and Treatment, at the Annual Meeting of the American-Psychiatric-Association CY MAY 22, 1993 CL SAN FRANCISCO, CA SP AMER PSYCHIAT ASSOC ID BEHAVIORAL-INHIBITION; PANIC DISORDER; GENETIC EPIDEMIOLOGY; ANXIETY DISORDERS; FOLLOW-UP; CHILDREN; AGORAPHOBIA; FAMILY; PREPAREDNESS; DIAGNOSIS AB Human beings are by nature social animals, but for some, social scrutiny is a source of extreme anguish. Those with social phobia, for example, suffer excessive and often disabling concern about potential and real social-evaluative threat. As new and effective therapies for this condition are pursued, there is a simultaneous movement to extend the understanding of this disorder's etiology. In psychiatry, as in the rest of medicine, this development of new treatments often occurs in parallel with increasing sophistication about causes of illness. Advances in one area typically inform and predictably lead to advances in the other. Social phobia is recognized as a relatively common and significantly impairing anxiety disorder. As with other psychiatric disorders, emerging models of the etiology of social phobia are derived from converging evidence of interacting biological and environmental contributions. Current theories regarding the evolution of social phobia will be addressed, including biological preparedness to fear scrutiny by others, genetically transmitted predisposition to fear acquisition, nongenetic familial and environmental factors, as well as other possible causes and antecedents. Additionally, we describe recent work on behavioral inhibition in infancy as an identifiable early marker of proneness to the development of anxiety disorders, including social phobia. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. RP ROSENBAUM, JF (reprint author), MASSACHUSETTS GEN HOSP,CLIN PSYCHOPHARMACOL CLIN,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 42 TC 36 Z9 37 U1 2 U2 9 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 1994 VL 55 SU S BP 10 EP 16 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA NZ644 UT WOS:A1994NZ64400003 PM 8077161 ER PT J AU KEUTHEN, NJ CYR, P RICCIARDI, JA MINICHIELLO, WE BUTTOLPH, ML JENIKE, MA AF KEUTHEN, NJ CYR, P RICCIARDI, JA MINICHIELLO, WE BUTTOLPH, ML JENIKE, MA TI MEDICATION WITHDRAWAL SYMPTOMS IN OBSESSIVE-COMPULSIVE DISORDER PATIENTS TREATED WITH PAROXETINE SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Letter ID ANTIDEPRESSANT WITHDRAWAL; SERTRALINE RP KEUTHEN, NJ (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PSYCHIAT,BOSTON,MA, USA. NR 9 TC 47 Z9 47 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 1994 VL 14 IS 3 BP 206 EP 207 DI 10.1097/00004714-199406000-00010 PG 2 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA NL869 UT WOS:A1994NL86900009 PM 8027419 ER PT J AU LITTLE, M MURPHY, JM JELLINEK, MS BISHOP, SJ ARNETT, HL AF LITTLE, M MURPHY, JM JELLINEK, MS BISHOP, SJ ARNETT, HL TI SCREENING 4-YEAR-OLD AND 5-YEAR-OLD CHILDREN FOR PSYCHOSOCIAL DYSFUNCTION - A PRELIMINARY-STUDY WITH THE PEDIATRIC SYMPTOM CHECKLIST SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE PEDIATRIC SYMPTOM CHECKLIST; PSYCHOSOCIAL SCREENING; PRESCHOOL CHILDREN ID BEHAVIOR PROBLEMS; PRIMARY CARE; 3-YEAR-OLD CHILDREN; PARENTING STRESS; RATING-SCALE; ROC ANALYSIS; PREVALENCE; INVENTORY; PSYCHOPATHOLOGY; STANDARDIZATION AB The validity and reliability of the Pediatric Symptom Checklist (PSC), a parent-completed psychosocial screening questionnaire, was examined in a sample of 115 four- to five-year-old pediatric outpatients. The current study assessed agreement between the PSC and the Child Behavior Checklist. These results in the preschool sample were compared with results obtained in a sample of 6- to 12-year-old patients in the same practices. Levels of agreement between the PSC and the Child Behavior Checklist were found to be acceptable and approximately equal to those obtained with older children. Rates of reliability were also equivalent. Results provide preliminary support for the validity of the PSC for screening 4- and 5-year-old children. C1 YALE UNIV,DEPT PSYCHOL,NEW HAVEN,CT 06520. TUFTS UNIV,ELIOT PEARSON SCH APPL CHILD DEV,MEDFORD,MA 02155. RP LITTLE, M (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,BOSTON,MA 02114, USA. NR 55 TC 27 Z9 27 U1 3 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 1994 VL 15 IS 3 BP 191 EP 197 PG 7 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA NQ321 UT WOS:A1994NQ32100007 ER PT J AU KOYASU, S AF KOYASU, S TI CD3(+)CD16(+)NK1.1(+)B220(+) LARGE GRANULAR LYMPHOCYTES ARISE FROM BOTH ALPHA-BETA-TCR(+)CD4(-)CD8(-) AND GAMMA-DELTA-TCR(+)CD4(-)CD8(-) CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; FC-EPSILON-RI; RECEPTOR ZETA-CHAIN; TYROSINE KINASE ACTIVATION; ALPHA-BETA+ THYMOCYTES; DELTA-T-CELLS; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; GAMMA-DELTA; BONE-MARROW AB Cultivation of CD4(-)CD8(-) double negative (DN) mouse thymocytes and splenocytes with recombinant interleukin 2 (IL2) in the absence of other stimulation results in the generation of DN-CD3/TCR(+)CD16(+)NK1.1(+)B220(+) large granular lymphocytes (LGL). Purified DN alpha-beta TCR(+) thymocytes and splenocytes are CD16(+)IL2R alpha(-)IL2R beta(+)NK1.1(+)B220(-)CD5(high). These cells are unique in that they express both CD16 and T cell receptor (TCR) which are usually mutually exclusive. In addition, they express the natural killer (NK) marker, NK1.1. Cultivation of these cells with IL2 for several days results in the generation of DN alpha-beta TCR(+)CD16(+)NK1.1(+) B220(+)CD5(-) LGL, suggesting that DN alpha-beta TCR(+) cells in thymus and spleen are the precursors of the DN LGL reported previously. DN gamma-delta TCR(+)CD16(-)NK1.1(-)B220(-)CD5(high) thymocytes and splenocytes also give rise to DN gamma-delta TCR(+)CD16(+)NK1.1(+)B220(+)CD5(-) LGL which, as shown previously with DN alpha-beta TCR(+) LGL cells, are cytotoxic against NK-sensitive YAC-1 cells. Cytotoxic activity is also induced through either CD16 or the gamma-delta TCR. DN alpha-beta TCR(+) and DN gamma-delta TCR(+) LGL cells are thus similar in phenotype to TCR(-) NK cells. DN alpha-beta TCR(+) thymocytes express low levels of the gamma subunit of the high affinity immunoglobulin E receptor (Fc epsilon RI gamma) molecule, an essential component of CD16 expression. Fc epsilon RI gamma expression is greatly enhanced after cultivation with IL2, resulting in a higher surface expression of CD16. In contrast to DN alpha-beta TCR(+) thymocytes, DN gamma-delta TCR(+) thymocytes do not express detectable CD16 or Fc epsilon RI gamma mRNA but expression of both is induced by cultivation with IL2, leading to the expression of CD16 on the surface. Whereas CD16 molecules on both DN alpha-beta TCR(+) and DN gamma-delta TCR(+) LGL are associated with only Fc epsilon RI gamma homodimers, the TCR on these cells are associated with an Fc epsilon RI gamma homodimer and/or CD33 zeta Fc epsilon RI gamma heterodimers. These results demonstrate that the Fc epsilon RI gamma subunit is a component of the TCR in a fraction of T lineage cells. RP KOYASU, S (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,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 [AI-19807, AI-33017] NR 97 TC 98 Z9 98 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 1 PY 1994 VL 179 IS 6 BP 1957 EP 1972 DI 10.1084/jem.179.6.1957 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NN510 UT WOS:A1994NN51000021 PM 8195719 ER PT J AU CICILA, GT RAPP, JP BLOCH, KD KURTZ, TW PRAVENEC, M KREN, V HONG, CC QUERTERMOUS, T NG, SC AF CICILA, GT RAPP, JP BLOCH, KD KURTZ, TW PRAVENEC, M KREN, V HONG, CC QUERTERMOUS, T NG, SC TI COSEGREGATION OF THE ENDOTHELIN-3 LOCUS WITH BLOOD-PRESSURE AND RELATIVE HEART-WEIGHT IN INBRED DAHL RATS SO JOURNAL OF HYPERTENSION LA English DT Article DE GENETIC HYPERTENSION; EPISTASIS; LINKAGE; SALT SENSITIVITY; CARDIAC HYPERTROPHY ID SPONTANEOUSLY HYPERTENSIVE RATS; VASOCONSTRICTOR PEPTIDE; CHROMOSOMAL ASSIGNMENT; GENETIC DETERMINATION; CDNA CLONING; RENIN GENE; SA-GENE; STRAINS; LINKAGE; POLYMORPHISM AB Objective: To determine whether the endothelin-1 or endothelin-3 genes are genetically linked with blood pressure and relative heart weight in segregating rat populations, in the context of an elevated dietary sodium chloride intake. Methods: Endothelin-1 and endothelin-3 genotypes of rats in segregating populations, derived from crosses of Dahl salt-sensitive (SS/Jr) rats with contrasting inbred strains, including Lewis rats, spontaneously hypertensive rats and Dahl salt-resistant (SR/Jr) rats, were determined using restriction fragment length polymorphisms. Segregating populations were fed a high (8%)-sodium chloride diet. Linkage of genotype with blood pressure or relative heart weight was determined by analysis of variance. Chromosomal location of the rat endothelin-3 gene was determined by genotyping a panel of recombinant inbred strains. Results: Two alleles for the endothelin-1 gene and three alleles for the endothelin-3 gene were identified. The endothelin-1 locus did not cosegregate with blood pressure or relative heart weight. The endothelin-3 locus cosegregated with blood pressure and relative heart weight in an SS/JrxF(1) (SS/JrxSR/Jr) population, but not in populations containing a higher percentage of genes from the SR/Jr strain. The endothelin-3 and seminal vesicle protein-1 loci were linked and located on rat chromosome 3. Conclusion: The endothelin-3 gene is, or is linked to, a locus on chromosome 3 that regulates blood pressure and relative heart weight in inbred Dahl rats, and these effects were strongly dependent on the genetic background. C1 UNIV MISSOURI, CTR COSMOPOLITAN INT DIABET, COLUMBIA, MO USA. BRISTOL MYERS SQUIBB PHARMACEUT RES INST, DEPT MACROMOLEC BIOCHEM, PRINCETON, NJ 08543 USA. MED COLL OHIO, DEPT PHYSIOL & MOLEC MED, TOLEDO, OH 43699 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, GEN MED SERV, CARDIAC UNIT, BOSTON, MA 02114 USA. UNIV CALIF SAN FRANCISCO, DEPT LAB MED, SAN FRANCISCO, CA 94143 USA. ACAD SCI CZECH REPUBL, INST PHYSIOL, PRAGUE, CZECH REPUBLIC. CHARLES UNIV, DEPT BIOL, PRAGUE, CZECH REPUBLIC. RP UNIV MISSOURI, DEPT INTERNAL MED, 1 HOSP DR, COLUMBIA, MO 65212 USA. RI Hong, Charles/C-9989-2010; Pravenec, Michal/B-1666-2012; Kren, Vladimir/H-8461-2014 FU NHLBI NIH HHS [HL45895, HL20176, HL35018] NR 54 TC 60 Z9 60 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0263-6352 EI 1473-5598 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 1994 VL 12 IS 6 BP 643 EP 651 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NV926 UT WOS:A1994NV92600004 PM 7963489 ER PT J AU WAGNER, N ENGEL, P VEGA, M TEDDER, TF AF WAGNER, N ENGEL, P VEGA, M TEDDER, TF TI LIGATION OF MHC CLASS-I AND CLASS-II MOLECULES CAN LEAD TO HETEROLOGOUS DESENSITIZATION OF SIGNAL-TRANSDUCTION PATHWAYS THAT REGULATE HOMOTYPIC ADHESION IN HUMAN-LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; COMPLEX CLASS-I; HUMAN B-CELLS; MONOCLONAL-ANTIBODIES; CROSS-LINKING; PHYSICAL ASSOCIATION; ANTIGEN PRESENTATION; CYTOPLASMIC DOMAIN; FUNCTIONAL-ROLE; HLA-DR AB Engagement of lymphocyte MHC class I and class II Ags activates an array of intracellular signal transduction pathways that up-regulates the activity of cell-surface adhesion receptors, resulting in homotypic cell-cell aggregation. In this study, engagement of MHC class I and class II molecules with specific mAbs was shown to also inhibit lymphocyte homotypic adhesion. Two mAbs reactive with class II Ag, homotypic adhesion blocking mAb (HAB)-2, and HAB-3, and one mAb reactive with class I Ag, HAB-4, were generated that inhibited homotypic adhesion of activated lymphocytes and B and T cell lines at concentrations as low as 0.1 mu g/ml. Binding of these mAbs resulted in heterologous desensitization of other surface signal transduction molecules as homotypic adhesion induced through class I, class II, CD19, CD20, CD39, CD40, Leu-13, and PMA was also inhibited. The spontaneous adhesion exhibited by some cell lines was also abrogated by binding of these mAbs. Abs that either induced, blocked, or had no effect on adhesion bound to distinct epitopes on class I, whereas the anti-class II mAbs recognized either distinct or overlapping epitopes. Thus, engagement of distinct epitopes on MHC molecules can result in homologous or heterologous desensitization of cell-surface signaling molecules. The induction or inhibition of homotypic adhesion through class I molecules did not require the presence of the cytoplasmic domain, as deletion of this portion of the class I molecule had no effect. In contrast, the transmembrane region was essential for signal transduction as the mAbs binding to a chimeric molecule in which the transmembrane and cytoplasmic domains of class I were exchanged with those of the HB15 molecule did not induce or inhibit homotypic adhesion. Although this report is the first demonstration that homotypic adhesion can be influenced in a negative manner through MHC molecules, these findings demonstrate a considerable level of cross-talk between MHC molecules and other cell-surface receptor systems and their signal transduction pathways, and suggests that MHC class I and class II molecules may serve important roles in the regulation of adhesive events during lymphocyte activation. C1 DUKE UNIV,MED CTR,DEPT IMMUNOL,DURHAM,NC 27710. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. AUTONOMOUS UNIV MADRID,HOSP PRINCESA,DEPT MOLEC BIOL,E-28049 MADRID,SPAIN. FU NCI NIH HHS [CA-34183, CA-54464]; NIAID NIH HHS [AI-26872] NR 74 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1994 VL 152 IS 11 BP 5275 EP 5287 PG 13 WC Immunology SC Immunology GA NM615 UT WOS:A1994NM61500013 PM 7514635 ER PT J AU MARCHANT, CD LOUGHLIN, AM LETT, SM TODD, CW WETTERLOW, LH BICCHIERI, R HIGHAM, S ETKIND, P SILVA, E SIBER, GR AF MARCHANT, CD LOUGHLIN, AM LETT, SM TODD, CW WETTERLOW, LH BICCHIERI, R HIGHAM, S ETKIND, P SILVA, E SIBER, GR TI PERTUSSIS IN MASSACHUSETTS, 1981-1991 - INCIDENCE, SEROLOGIC DIAGNOSIS, AND VACCINE EFFECTIVENESS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID WHOOPING-COUGH; BORDETELLA; INFECTION; IMMUNIZATION; CHILDREN; ANTIGENS; EFFICACY; INFANTS; ADULTS; ASSAY AB Massachusetts provides diphtheria-tetanus toxoid-pertussis (DTP) vaccine, and since 1980 has monitored pertussis with a statewide diagnostic service. The incidence of bacteriologically confirmed pertussis was 104.5 per 100,000 person-years in 1-month-old infants and declined progressively thereafter. Infants <6 months old experienced disproportionate morbidity: 44% of bacteriologically confirmed pertussis, 64% of hospitalizations, and 71% of hospital days. Most children with pertussis had received <3 DTP doses during childhood, whereas 87% of adolescents with pertussis had received greater than or equal to 4 doses. Serodiagnosis by single serum anti-pertussis toxin antibody ELISA increased the incidence of confirmed pertussis in persons 11-19 years old from 3.0 to 12.9 per 100,000 and in persons greater than or equal to 20 years old from 0.16 to 0.56 per 100,000. Bacteriologic methods underestimate pertussis incidence, but a single serum anti-pertussis toxin antibody ELISA is a practical method for population-based diagnosis in adolescents and adults. C1 MASSACHUSETTS PUBL HLTH BIOL LABS,BOSTON,MA. MASSACHUSETTS DEPT PUBL HLTH,DIV COMMUNICABLE DIS,BOSTON,MA. MASSACHUSETTS DEPT PUBL HLTH,MASSACHUSETTS CTR DIS CONTROL,BUR LABS & ENVIRONM SCI,BOSTON,MA. TUFTS UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02111. HARVARD UNIV,SCH MED,BOSTON,MA. NR 33 TC 93 Z9 97 U1 0 U2 0 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 JUN PY 1994 VL 169 IS 6 BP 1297 EP 1305 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NX991 UT WOS:A1994NX99100016 PM 8195607 ER PT J AU SIBER, GR LEOMBRUNO, D LESZCZYNSKI, J MCIVER, J BODKIN, D GONIN, R THOMPSON, CM WALSH, EE PIEDRA, PA HEMMING, VG PRINCE, GA AF SIBER, GR LEOMBRUNO, D LESZCZYNSKI, J MCIVER, J BODKIN, D GONIN, R THOMPSON, CM WALSH, EE PIEDRA, PA HEMMING, VG PRINCE, GA TI COMPARISON OF ANTIBODY CONCENTRATIONS AND PROTECTIVE ACTIVITY OF RESPIRATORY SYNCYTIAL VIRUS IMMUNE GLOBULIN AND CONVENTIONAL IMMUNE GLOBULIN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID RISK; INFECTION; CHILDREN; INFANTS AB Relative to conventional immune globulins (IG, 13 lots), IGs prepared from donors with high activity by microneutralization assay to respiratory syncytial virus (RSVIG, 8 lots) had significantly higher neutralizing antibodies to 6 RSV strains (mean enrichment, 5.2-fold; range, 2.6- to 10.0-fold). In contrast, IgG antibody concentrations to whole RSV, fusion protein, or glycoproteins of A and B strains were similar in RSVIG and IG. Treatment of cotton rats with RSVIG at 0.5 g/kg 24 h before RSV challenge reduced RSV by 99% in the lungs (P < .001). RSVIG at 5.0 g/kg reduced RSV by 99% in the nose. IG at 5.0 g/kg had efficacy similar to that of RSVIG at 0.5 g/kg. Serum plaque-reduction neutralization titers of 1/390 resulted in 99% reduction of lung RSV and titers of 1/3500 resulted in 99% reduction in nose RSV. Relative to IG, RSVIG is enriched selectively in RSV neutralizing antibodies and has similar to 10 times greater protective activity in cotton rats. C1 DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. UNIFORMED SERV UNIV HLTH SCI,DEPT PEDIAT,BETHESDA,MD 20814. VIR SYST INC,ROCKVILLE,MD. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. UNIV ROCHESTER,DEPT MED,ROCHESTER,NY. RP SIBER, GR (reprint author), MASSACHUSETTS PUBL HLTH BIOL LABS,305 SOUTH ST,BOSTON,MA 02130, USA. NR 13 TC 96 Z9 97 U1 0 U2 2 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 JUN PY 1994 VL 169 IS 6 BP 1368 EP 1373 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NX991 UT WOS:A1994NX99100030 PM 8195619 ER PT J AU DEKKER, SK VINK, J VERMEER, BJ BRUIJN, JA MIHM, MC BYERS, HR AF DEKKER, SK VINK, J VERMEER, BJ BRUIJN, JA MIHM, MC BYERS, HR TI DIFFERENTIAL-EFFECTS OF INTERLEUKIN-1-ALPHA (IL-1-ALPHA) OR TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) ON MOTILITY OF HUMAN-MELANOMA CELL-LINES ON FIBRONECTIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE MIGRATION; TUMOR NECROSIS FACTOR; INTERLEUKIN 1; INTEGRIN ID MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; METASTATIC MELANOMA; ENDOTHELIAL-CELLS; FACTOR RECEPTOR; INTEGRIN VLA-4; ADHESION; EXPRESSION; MIGRATION; BINDING AB Interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor-alpha (TNF-alpha) induce a motogenic response in a number of benign and malignant cells. We examined the chemokinetic effects of these cytokines on the cell migration of four melanoma cell lines on fibronectin using modified Boyden chambers and video-time lapse analysis. Flow cytometry analysis of IL-1 receptors, TNF receptors, and shifts in beta(1) integrin expression were correlated with the effects of these cytokines on cell migration on fibronectin. The four melanoma cell lines exhibited heterogeneous expression of types I and II IL-1 receptors as well as p60 TNF receptors. Scant p80 TNF receptor expression was detected on only one cell line. Three of four melanoma cell lines demonstrated type I IL-1 receptors by Western blotting. IL-1 alpha and TNF-alpha induced heterogeneous modulation of beta(1) integrin expression in the four melanoma cell lines tested; downward shift of the alpha(2), alpha(3), alpha(4), and beta(1) integrin subunits was detected among three of the melanoma cell lines as were upward shifts of the alpha(4), alpha(5), and alpha(6) integrin subunits among three of the melanoma cell lines. IL-1 alpha and TNF-alpha induced enhanced migration of fibronectin in one of the melanoma cell lines and were related to an upward shift in the alpha(4) and alpha(5) integrin subunit expression. Taken together, the findings indicate that expression of a particular receptor for IL-1 or TNF does not necessarily signal a motogenic response in melanoma cells, but induces heterogeneous shifts in beta(1) integrin expression. However, up-regulation in alpha(4) and alpha(5) integrin subunits appears to relate to enhanced migration on fibronectin., C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,DIV DERMATOPATHOL,BOSTON,MA 02115. LEIDEN UNIV,DEPT DERMATOL,LEIDEN,NETHERLANDS. LEIDEN UNIV,DEPT PATHOL,LEIDEN,NETHERLANDS. FU NCI NIH HHS [CA-45587] NR 43 TC 17 Z9 17 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1994 VL 102 IS 6 BP 898 EP 905 DI 10.1111/1523-1747.ep12383385 PG 8 WC Dermatology SC Dermatology GA NT864 UT WOS:A1994NT86400015 PM 8006453 ER PT J AU GRABBE, S BRUVERS, S BEISSERT, S GRANSTEIN, RD AF GRABBE, S BRUVERS, S BEISSERT, S GRANSTEIN, RD TI INTERFERON-GAMMA INHIBITS TUMOR-ANTIGEN PRESENTATION BY EPIDERMAL ANTIGEN-PRESENTING CELLS SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE LANGERHANS CELLS; TUMOR IMMUNITY; ANTIGEN PRESENTATION; INTERFERON-GAMMA; MICE ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; PROTEIN-KINASE-C; LANGERHANS CELLS; ULTRAVIOLET-RADIATION; ENDOTOXIN RESISTANCE; PHORBOL ESTER; DTH REACTION; INDUCTION; EXPRESSION AB Murine I-A(+) epidermal antigen-presenting cells (APCs) have been shown to be capable of presenting soluble tumor fragments (TFs), as a source of tumor-associated antigens (TAAs), for primary and secondary tumor immune responses. In this study we investigated whether incubation of epidermal APCs in interferon-gamma (IFN-gamma) modulates their ability to present TAA and whether the effects of IFN-gamma on the presentation of tumor antigen correspond to its effects on alloantigen presentation in both primed and unprimed systems. Our results show that three weekly subcutaneous injections of naive mice with GM-CSF-cultured but not with fresh TAA-pulsed epidermal APCs induce protective tumor immunity in naive mice and that the immunostimulatory effect of GM-CSF in this system is abrogated by coculture of epidermal cells in IFN-gamma. Furthermore, epidermal APCs are able to present TAA to primed, tumor-immune mice, as assessed by the elicitation of tumor-specific delayed-type hypersensitivity after injection of TAA-pulsed epidermal APCs. IFN-gamma was found to inhibit tumor antigen presentation by freshly prepared epidermal APCs in this system. The effects of IFN-gamma on the presentation of tumor antigen correlated well with its effects on the primary and secondary mixed epidermal cell-lymphocyte reaction, indicating that IFN-gamma differentially modulates the function of epidermal APCs with regard to induction versus elicitation of immunity. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,DEPT DERMATOL,BOSTON,MA 02129. FU NIAMS NIH HHS [AR40667] NR 48 TC 27 Z9 28 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JUN PY 1994 VL 55 IS 6 BP 695 EP 701 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA NP106 UT WOS:A1994NP10600002 PM 8195694 ER PT J AU ENG, C MURDAY, V SEAL, S MOHAMMED, S HODGSON, SV CHAUDARY, MA FENTIMAN, IS PONDER, BAJ EELES, RA AF ENG, C MURDAY, V SEAL, S MOHAMMED, S HODGSON, SV CHAUDARY, MA FENTIMAN, IS PONDER, BAJ EELES, RA TI COWDEN SYNDROME AND LHERMITTE-DUCLOS DISEASE IN A FAMILY - A SINGLE GENETIC SYNDROME WITH PLEIOTROPY SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID LI-FRAUMENI SYNDROME; P53 GENE; MUTATIONS; CANCERS AB Cowden syndrome is an autosomal dominant condition of multiple hamartomas. Patients with this phakomatosis have an increased risk of breast cancer and thyroid tumours. Lhermitte-Duclos disease is usually a sporadic condition of cerebellar ganglion cell hypertrophy, ataxia, mental retardation, and self-limited seizure disorder. We describe a three generation family with Cowden syndrome and Lhermitte-Duclos disease. Karyotyping performed on the peripheral lymphocytes of the proband and her affected mother showed a 46,XX complement. Single strand conformational polymorphism analysis failed to show any germline p53 mutations as a cause of the syndrome in this family. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,DIV MED ONCOL,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. ST GEORGE HOSP,SCH MED,SW THAMES REG GENET SERV,LONDON,ENGLAND. GUYS HOSP,SE THAMES REG GENET CTR,LONDON SE1 9RT,ENGLAND. GUYS HOSP,IMPERIAL CANC RES FUND,CLIN ONCOL UNIT,LONDON SE1 9RT,ENGLAND. ROYAL MARSDEN HOSP,ACAD UNIT RADIOTHERAPY & ONCOL,CRC,SUTTON SM2 5PT,SURREY,ENGLAND. INST CANC RES,MOLEC CARCINOGENESIS SECT,SUTTON SM2 5NG,SURREY,ENGLAND. RP ENG, C (reprint author), UNIV CAMBRIDGE,DEPT PATHOL,CRC,HUMAN CANC GENET RES GRP,TENNIS COURT RD,CAMBRIDGE CB2 1QP,ENGLAND. OI Eng, Charis/0000-0002-3693-5145 NR 24 TC 78 Z9 78 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUN PY 1994 VL 31 IS 6 BP 458 EP 461 DI 10.1136/jmg.31.6.458 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA NP423 UT WOS:A1994NP42300006 PM 8071972 ER PT J AU SNYDER, SL ROSENBAUM, DH ROWAN, AJ STRAIN, JJ AF SNYDER, SL ROSENBAUM, DH ROWAN, AJ STRAIN, JJ TI SCID DIAGNOSIS OF PANIC DISORDER IN PSYCHOGENIC SEIZURE PATIENTS SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID HYSTERICAL SEIZURES; DSM-III; PSEUDOSEIZURES AB The authors administered the Structured Clinic Interview for DSM-III-R (SCID) to 20 outpatients with nonepileptic seizures documented by video-EEG. Fourteen (70%) had one or more non-somatoform DSM-III-R diagnoses. All 14 met criteria for panic disorder. Comorbid mood, psychotic, substance abuse, and eating disorders were also noted. Meticulous use of the SCID, with extensive follow-up, may have resulted in enhanced detection of panic disorder in patients who do not spontaneously report panic symptoms. Panic attacks may play a more important role in nonepileptic seizures than has been generally recognized, especially in outpatients with a chronic course of illness. C1 MT SINAI MED CTR,DEPT NEUROL,NEW YORK,NY 10029. BRONX VET AFFAIRS MED CTR,DEPT NEUROL,BRONX,NY. RP SNYDER, SL (reprint author), MT SINAI MED CTR,DEPT PSYCHIAT,DIV BEHAV MED & CONSULTAT PSYCHIAT,BOX 1228,1 G L LEVY PL,NEW YORK,NY 10029, USA. NR 31 TC 30 Z9 30 U1 1 U2 3 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 SUM PY 1994 VL 6 IS 3 BP 261 EP 266 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NY895 UT WOS:A1994NY89500007 PM 7950349 ER PT J AU SCHMIDT, CJ ZUBIAUR, M VALENZUELA, D NEER, EJ DRAGER, UC AF SCHMIDT, CJ ZUBIAUR, M VALENZUELA, D NEER, EJ DRAGER, UC TI G(O), A GUANINE-NUCLEOTIDE-BINDING PROTEIN, IS EXPRESSED DURING NEURITE EXTENSION IN THE EMBRYONIC MOUSE SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE G PROTEINS; GAP43; EMBRYONIC MOUSE; BRAIN; HEART; DEVELOPMENT ID NERVOUS-SYSTEM; MOLECULAR CHARACTERIZATION; ALPHA-SUBUNITS; GROWTH CONE; G0; TRANSDUCTION; GAP-43 AB The developmental pattern of expression of the G protein alpha(O) subunit and GAP43 were compared by immunohistochemical staining of mouse embryos. Staining for alpha(O) and GAP43 was identical and detected throughout the developing nervous system, and the antigens first appeared in neurons at the beginning of neuronal differentiation. GAP43 and alpha(O) were not detected in regions containing only neuroblasts. These observations suggest that alpha(O) and GAP43 may not be required for the decision to pass from neuroblast to differentiated neuron, but may play a role in signal transduction during early neuronal development. (C) 1994 Wiley-Liss, Inc. C1 HARVARD UNIV, SCH MED, DEPT NEUROBIOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEV BIOL LAB, BOSTON, MA USA. RP BRIGHAM & WOMENS HOSP, DEPT MED, DIV CARDIOVASC, 75 FRANCIS ST, BOSTON, MA 02115 USA. RI Zubiaur, Mercedes/K-9390-2014; OI Zubiaur, Mercedes/0000-0002-4127-3027; Drager, Ursula C/0000-0003-1815-190X FU NEI NIH HHS [EY01938]; NIGMS NIH HHS [GM46370, GM36295] NR 28 TC 14 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0360-4012 EI 1097-4547 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 1 PY 1994 VL 38 IS 2 BP 182 EP 187 DI 10.1002/jnr.490380208 PG 6 WC Neurosciences SC Neurosciences & Neurology GA NM078 UT WOS:A1994NM07800007 PM 8078103 ER PT J AU NARULA, J NICOL, PD SOUTHERN, JF PIERI, P ODONNELL, SM GUERERRO, JL NOSSIFF, ND NEWELL, JB STRAUSS, HW KHAW, BA AF NARULA, J NICOL, PD SOUTHERN, JF PIERI, P ODONNELL, SM GUERERRO, JL NOSSIFF, ND NEWELL, JB STRAUSS, HW KHAW, BA TI EVALUATION OF MYOCARDIAL INFARCT SIZE BEFORE AND AFTER REPERFUSION - DUAL-TRACER IMAGING WITH RADIOLABELED ANTIMYOSIN ANTIBODY SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE MYOCARDIAL INFARCT SIZE; ANTIMYOSIN ANTIBODY; MYOCARDIAL REPERFUSION ID MYOSIN-SPECIFIC ANTIBODY; SUPEROXIDE-DISMUTASE; CARDIAC MYOSIN; FREE-RADICALS; ISCHEMIC MYOCARDIUM; MONOCLONAL-ANTIBODY; IN-111 ANTIMYOSIN; INJURY; CHLORPROMAZINE; CELL AB Antimyosin antibody is a specific marker of myocardial necrosis that is based on the loss of integrity of the sarcolemmal membrane. Because antimyosin can be labeled with several different radiotracers, gamma imaging performed with antimyosin labeled with two different radionuclides can be used to quantify infarct size before and after an intervention such as reperfusion. Methods: Twelve open-chested anesthetized dogs were evaluated both at the end of 1.5 hr of occlusion of the left anterior descending coronary artery and following reperfusion. Antimyosin Fab radiolabeled with either I-123 or In-111 was injected by intracoronary administration over 3 min at the end of the occlusion interval, and the coronary sinus was drained continuously for 7 min to prevent recirculation of the antibody. One hour after reperfusion, a second injection of antimyosin Fab (labeled with a different isotope from the first) was administered as before. Six dogs were given intracoronary trifluoperazine (150 mu g/kg of body weight) simultaneously with reperfusion, and another six dogs received saline as the control. The infarct size in grams before and after reperfusion was assessed by antimyosin antibody up take in ex vivo images of 1-cm thick slices of the hearts. The mean infarct sizes before (W1) and after (W2) reperfusion were then calculated as the percent of infarcted myocardium/ventricular myocardial mass. Results: There was a significant increase in the mean percent infarct size after reperfusion in the control group (W2 = 16.73 +/- 4.0, W1 = 14.92 +/- 3.88; p = 0.029). The mean infarct size was uniformly smaller with trifluoperazine intervention (W2 = 12.33 +/- 2.03, W1 = 16.34 +/- 2.78; p = 0.004). The difference between the mean change in the infarct sizes in the two groups was highly significant (p = 0.002). Conclusion: Dual imaging of the extent of myocardial necrosis before and after an intervention (reperfusion) in the same animal demonstrated the utility of antimyosin imaging to document changes in the extent of necrosis. C1 NORTHEASTERN UNIV,BOUVE COLL PHARM & HLTH SCI,CTR DRUG TARGETING & ANAL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DIV NUCL MED,CARDIAC UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 48 TC 9 Z9 9 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 JUN PY 1994 VL 35 IS 6 BP 1076 EP 1085 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NP288 UT WOS:A1994NP28800030 PM 8195873 ER PT J AU CHANDLER, HL AF CHANDLER, HL TI POTSAID,MAJIC,S. - NOVEMBER 20, 1916 FEBRUARY 13, 1994 - MEMORIAM SO JOURNAL OF NUCLEAR MEDICINE LA English DT Item About an Individual RP CHANDLER, HL (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 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 JUN PY 1994 VL 35 IS 6 BP A41 EP A41 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NP288 UT WOS:A1994NP28800032 ER PT J AU HOLMBERG, EB HILLMAN, RE PERKELL, JS GRESS, C AF HOLMBERG, EB HILLMAN, RE PERKELL, JS GRESS, C TI RELATIONSHIPS BETWEEN INTRA-SPEAKER VARIATION IN AERODYNAMIC MEASURES OF VOICE PRODUCTION AND VARIATION IN SPL ACROSS REPEATED RECORDINGS SO JOURNAL OF SPEECH AND HEARING RESEARCH LA English DT Article DE SPEAKER VARIATION; GLOTTAL WAVE-FORM; SUBGLOTTAL AIR PRESSURE; VOCAL INTENSITY; VOICE PRODUCTION ID GLOTTAL AIR-FLOW; PRESSURE; FEMALE; PERCEPTION; WAVE AB Intra-speaker variation in aerodynamic and acoustic measures of voice Production across repeated recordings was studied in relation to cross-recording vari ion in SPL for three normal female and three normal male speakers. Group data for 15 females and 15 males served as the statistical reference. The speech material consisted of syllable strings soft, normal, and loud voice, Measures were made of (a) parameters characterizing the inverse filtered oral airflow waveform, (b) the inferred average transgiottal air pressure and glottal airflow, and (c) SPL. The results showed that intra-speaker parameter variation across recordings was generally less than 2 standard deviations relative to group mean values. In terms of relation to variation in SPL, the measures could be divided into two main groups: (a) For air pressure, AC flow, and maximum flow declination rate, both intra-speaker variation across recordings and inter-speaker (group) variation was related systematically to variation of SPL. For these measures, it is suggested that variation across recordings was due in part to SPL differences, which can be adjusted for statistically, thus facilitating comparisons between absolute values. (b) For other measures, neither intra-speaker variation across recordings nor inter-speaker group variation was systematically related to SPL. However, some of these latter measures changed with SPL in an orderly fashion across soft, normal, and loud voice for individual speakers. The results are discussed in terms of the clinical use of these measures in studies of voice disorders. C1 MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP HOLMBERG, EB (reprint author), MASSACHUSETTS EYE & EAR INFIRM,VOICE & SPEECH LAB,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC00266] NR 33 TC 40 Z9 40 U1 0 U2 1 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 JUN PY 1994 VL 37 IS 3 BP 484 EP 495 PG 12 WC Language & Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA NP965 UT WOS:A1994NP96500001 PM 8084180 ER PT J AU NICKMAN, SL LEWIS, RG AF NICKMAN, SL LEWIS, RG TI ADOPTIVE FAMILIES AND PROFESSIONALS - WHEN THE EXPERTS MAKE THINGS WORSE SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article RP NICKMAN, SL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 6 TC 10 Z9 10 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 JUN PY 1994 VL 33 IS 5 BP 753 EP 755 DI 10.1097/00004583-199406000-00017 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NN869 UT WOS:A1994NN86900017 PM 8056739 ER PT J AU FERNANDEZORTIZ, A BADIMON, JJ FALK, E FUSTER, V MEYER, B MAILHAC, A WENG, D SHAH, PK BADIMON, L AF FERNANDEZORTIZ, A BADIMON, JJ FALK, E FUSTER, V MEYER, B MAILHAC, A WENG, D SHAH, PK BADIMON, L TI CHARACTERIZATION OF THE RELATIVE THROMBOGENICITY OF ATHEROSCLEROTIC PLAQUE COMPONENTS - IMPLICATIONS FOR CONSEQUENCES OF PLAQUE RUPTURE SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; VESSEL WALL; SHEAR RATE; PLATELET DEPOSITION; THROMBUS FORMATION; TISSUE FACTOR; VONWILLEBRAND-FACTOR; BLOOD-COAGULATION; ENDOTHELIAL-CELLS AB Objectives. The purpose of this study was to determine whether different components of human atherosclerotic plaques exposed to flowing blood resulted in different degrees of thrombus formation. Background. It is likely that the nature of the substrate exposed after spontaneous or angioplasty induced plaque rupture is one factor determining whether an unstable plaque proceeds rapidly to an occlusive thrombus or persists as a nonocclusive mural thrombus. Although observational data show that plaque rupture is a potent stimulus for thrombosis, and exposed collagen is suggested to have a predominant role in thrombosis, the relative thrombogenicity of different components of human atherosclerotic plaques is not well established. Methods. We investigated thrombus formation on foam cell rich matrix (obtained from fatty streaks), collagen-rich matrix (from sclerotic plaques), collagen poor matrix without cholesterol crystals (from fibrolipid plaques), atheromatous core with abundant cholesterol crystals (from atheromatous plaques) and segments of normal intima derived from human aortas at necropsy. Specimens were mounted in a tubular chamber placed within an ex vivo extracorporeal perfusion system and exposed to heparinized porcine blood (mean [+/-SEM] activated partial thromboplastin time ratio 1.5 +/- 0.04) for 5 min under high shear rate conditions (1,690 s(-1)). Thrombus was quantitated by measurement of indium-labeled platelets and morphometric analysis. Under similar conditions, substrates were perfused with heparinized human blood (2 IU/ml) in an in vitro system, and thrombus formation was similarly evaluated. Results. Thrombus formation on atheromatous core was up to sixfold greater than that on other substrates, including collagen rich matrix (p = 0.0001) in both heterologous and homologous systems. Although the atheromatous core had a more irregular exposed surface and thrombus formation tended to increase with increasing roughness, the atheromatous core remained the most thrombogenic substrate when the substrates were normalized by the degree of irregularity as defined by the roughness index (p 0.002). Conclusions. The atheromatous core is the most thrombogenic component of human atherosclerotic plaques. Therefore, plaques with a large atheromatous core content are at high risk of leading to acute coronary syndromes after spontaneous or mechanically induced rupture because of the increased thrombogenicity of their content. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIOVASC BIOL LAB,BOSTON,MA 02114. RI BADIMON, LINA/O-4711-2014; Falk, Erling/A-7475-2015; Fuster, Valentin/H-4319-2015; Fernandez-Ortiz, Antonio/B-2227-2017 OI BADIMON, LINA/0000-0002-9162-2459; Falk, Erling/0000-0001-8566-9974; Fuster, Valentin/0000-0002-9043-9986; Fernandez-Ortiz, Antonio/0000-0002-3239-1910 FU NHLBI NIH HHS [HL-38933] NR 35 TC 413 Z9 423 U1 3 U2 12 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 JUN PY 1994 VL 23 IS 7 BP 1562 EP 1569 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH374 UT WOS:A1994PH37400008 PM 8195515 ER PT J AU TUZCU, EM BLOCK, PC GRIFFIN, B DINSMORE, R NEWELL, JB PALACIOS, IF AF TUZCU, EM BLOCK, PC GRIFFIN, B DINSMORE, R NEWELL, JB PALACIOS, IF TI PERCUTANEOUS MITRAL BALLOON VALVOTOMY IN PATIENTS WITH CALCIFIC MITRAL-STENOSIS - IMMEDIATE AND LONG-TERM OUTCOME SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID REGURGITATION; VALVULOPLASTY AB Objectives. This study analyzed the immediate and long-term outcome of percutaneous balloon mitral valvotomy in patients with and without fluoroscopically visible mitral valve calcification. Background. Mitral valve calcification has been Shown to be an important factor in determining immediate and long-term out come of patients undergoing surgical mitral commissurotomy. Patient selection has an important impact on the outcome of percutaneous balloon mitral valvotomy. Methods. The immediate and long term results of percutaneous balloon mitral valvotomy were compared in 155 patients with and 173 patients without mitral valve calcification. The patients with calcified valves were assigned to four groups according to severity of calcification. Results. Patients with calcified mitral stenosis more frequently were in New York Heart Association functional class III or IV and more frequently had atrial fibrillation, previous surgical commissurotomy, echocardiographic score >8, higher pulmonary artery and left atrial pressures, higher pulmonary vascular resistance and mean mitral valve gradient and lower cardiac output and smaller mitral valve area. Mitral valve area after valvotomy was significantly smaller in patients with calcified valves (1.8 +/- 0.06 vs. 2.1 +/- 0.06 cm(2)) and was;greater than or equal to 1.5 cm(2) in 65% of patients with and 83% of patients without calcified valves (p = 0.004). A successful outcome, defined as mitral valve area >1.5 cm(2) without significant mitral regurgitation and left to right shunting, was achieved in 52% of patients with and 69% of patients without uncalcified valves (p = 0.001). The success rate was 59%, 48%, 35% and 33% in subgroups with 1+, 2+, 3+ and 4+ calcification, respectively. The rates of significant left to right shunting and mitral regurgitation after valvuloplasty were similar in the two groups. Estimated survival rate (80% vs. 99%, respectively, p = 0.0001), survival rate without mitral valve replacement (67% vs. 93%, respectively, p < 0.00005) and event-free survival rate (63% vs. 88%, respectively, p < 0.00005) at 2 years were significantly better in the patients with uncalcified valves. Survival rate curves became progressively worse as the severity of calcification increased. Conclusions. These findings indicate that immediate and longterm results of mitral valvuloplasty are not as successful in patients with fluoroscopically visible mitral valve calcification as in those without calcification. C1 MASSACHUSETTS GEN HOSP,DEPT MED,CARDIAC UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 18 TC 52 Z9 52 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 JUN PY 1994 VL 23 IS 7 BP 1604 EP 1609 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH374 UT WOS:A1994PH37400014 PM 8195521 ER PT J AU JIANG, L DEPRADA, JAV HANDSCHUMACHER, MD GUERERRO, JL VLAHAKES, GJ KING, ME WEYMAN, AE LEVINE, RA AF JIANG, L DEPRADA, JAV HANDSCHUMACHER, MD GUERERRO, JL VLAHAKES, GJ KING, ME WEYMAN, AE LEVINE, RA TI 3-DIMENSIONAL ECHOCARDIOGRAPHY - IN-VIVO VALIDATION FOR RIGHT-VENTRICULAR FREE-WALL MASS AS AN INDEX OF HYPERTROPHY SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID EJECTION FRACTION; REAL-TIME; 3-DIMENSIONAL RECONSTRUCTION; VOLUME; THICKNESS; DISEASE; CHILDREN; IMAGES; SYSTEM; HEART AB Objectives. This study tested the ability of three dimensional echocardiography to reconstruct the right ventricular free wall and determine its mass in vivo using a system that automatically combines two dimensional images with their spatial locations. Background. Right ventricular free wall thickness is limited as an index of right ventricular hypertrophy because right ventricular mass may increase by dilation without increased thickness and because trabeculations and oblique views can exaggerate thickness in individual M mode and two dimensional scans. Three dimensional echocardiography may have potential advantages because it can integrate the entire free wall mass, uninfluenced by oblique views or geometric assumptions. Methods. The three dimensional system was applied to 12 beating canine hearts to reconstruct the right ventricular free wall in intersecting views. The corresponding mass was compared with actual weights of the excised right ventricular free wall (15.5 to 78 g), For comparison, right ventricular sinus and outflow tract thickness were also measured by two dimensional echocardiography, and the ability to predict mass from these values was determined. Results. The three dimensional algorithm successfully reproduced right ventricular free wall mass, which agreed well with actual values: y = 1.04x + 0.02, r = 0.985, SEE = 2.7 g (5.7% of the mean value). The two dimensional predictions showed increased scatter: The variance of mass estimation, based on thickness, was 9.5 to 12.5 (average 11) times higher than the three dimensional method (p < 0.02). Conclusions. Despite the irregular crescentic shape of the right ventricle, its free wall mass can be accurately measured by three dimensional echocardiography in vivo, providing closer agreement with actual mass than predictions based on wall thickness. This method, with the increased efficiency of the three dimensional system, can potentially improve our ability to evaluate the presence and progression of right ventricular hypertrophy. RP JIANG, L (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIAC ULTRASOUND LAB,VINCENT BURNHAM 5,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL-38176] NR 53 TC 34 Z9 36 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 JUN PY 1994 VL 23 IS 7 BP 1715 EP 1722 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH374 UT WOS:A1994PH37400031 PM 8195537 ER PT J AU ABBATE, M BACHINSKY, DR MCCLUSKEY, RT BROWN, D AF ABBATE, M BACHINSKY, DR MCCLUSKEY, RT BROWN, D TI EXPRESSION OF GP330 AND GP330/ALPHA(2)-MACROGLOBULIN RECEPTOR-ASSOCIATED PROTEIN IN RENAL TUBULAR DIFFERENTIATION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE GP330; GP330-ALPHA(2)-MACROGLOBULIN RECEPTOR-ASSOCIATED PROTEIN; PROXIMAL TUBULE; EXOCYTOSIS; NEPHRON DEVELOPMENT ID NEPHRITIS ANTIGENIC COMPLEX; BRUSH-BORDER ANTIGENS; HEYMANN NEPHRITIS; ALPHA-2-MACROGLOBULIN RECEPTOR; MONOCLONAL-ANTIBODIES; MEMBRANE GLYCOPROTEIN; AUTOANTIGEN GP330; EPITHELIAL-CELLS; PROXIMAL TUBULES; INVARIANT CHAIN AB The gp330/alpha(2)-macroglobulin receptor-associated protein (RAP) is a 39- to 45-kd protein that binds to the low-density lipoprotein receptor-related protein/ alpha(2)-macroglobulin receptor and to gp330, a major glycoprotein of the brush border of proximal tubule cells. Despite evidence that gp330 functions as a receptor for several ligands and that soluble RAP inhibits ligand binding to gp330 in vitro, the physiologic function of RAP is unknown. Given the predominant location of RAP within the rough endoplasmic reticulum (RER), RAP might be involved in the intracellular processing and/or transport of gp330. The developing rat kidney was used as a dynamic model to study in detail the relationship between gp330 and RAP in vivo by immunohistochemical techniques. RAP was expressed in the renal vesicle and continued to be present, with a vesicular and perinuclear pattern of staining, in both proximal tubule cells and glomerular cells at subsequent stages. Immunoperoxidase electron microscopy demonstrated RAP in cisternae of the RER and in large subapical vesicles. gp330 was initially expressed in early proximal tubule cells in S-shaped bodies and was located in the perinuclear envelope and cytoplasmic vesicles as well as at the apical surface. Cytoplasmic gp330 staining was more evident at a stage subsequent to the S-shaped body, possibly related to more active biosynthesis. By comparative analysis of the patterns of immunofluorescence and immunoperoxidase staining, gp330 and RAP colocalized in the RER and in some large subapical vacuoles, but no definite RAP staining could be detected at the surface of proximal tubule cells at any stage, despite the presence of abundant gp330 in this location. The expression of gp330 at the apical surface of immature tubular cells was associated with the onset of fluid-phase endocytosis of fluoroscein isothiocyanate-dextran and, therefore, of reabsorption of material from the tubular lumen, in the absence of concomitant changes in RAP expression in the same cells. These findings indicate that the role of endogenous RAP may not be directly related to ligand binding of gp330 at the surface of proximal tubule cells, although RAP may be involved in the processing and the intracellular trafficking of newly synthesized gp330, in particular in the delivery of gp330 to the plasma membrane. C1 MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. FU NIDDK NIH HHS [DK42956, DK46301] NR 45 TC 10 Z9 10 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 1994 VL 4 IS 12 BP 2003 EP 2015 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA NT872 UT WOS:A1994NT87200009 PM 7522607 ER PT J AU MITCHELL, JD LEE, R HODAKOWSKI, GT NEYA, K HARRINGER, W VALERI, CR VLAHAKES, GJ AF MITCHELL, JD LEE, R HODAKOWSKI, GT NEYA, K HARRINGER, W VALERI, CR VLAHAKES, GJ TI PREVENTION OF POSTOPERATIVE PERICARDIAL ADHESIONS WITH A HYALURONIC-ACID COATING SOLUTION - EXPERIMENTAL SAFETY AND EFFICACY STUDIES SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID POLYTETRAFLUOROETHYLENE SURGICAL MEMBRANE; PERITONEAL FIBRINOLYTIC-ACTIVITY; TISSUE PLASMINOGEN-ACTIVATOR; INTRAABDOMINAL ADHESIONS; SODIUM HYALURONATE; CLOSURE; MODEL; OPERATIONS; ABILITY; SURGERY AB Postoperative pericardial adhesions complicate reoperative cardiac procedures. Topical application of solutions containing hyaluronic acid have been shown to reduce adhesions after abdominal and orthopedic surgery. The mechanism by which hyaluronic acid solutions prevent adhesion formation is unknown but may be due to a cytoprotective effect on mesothelial surfaces, which would Limit intraoperative injury. In this study, we tested the efficacy and safety of hyaluronic acid coating solutions for the prevention of postoperative intrapericardial adhesion formation. Eighteen mongrel dogs underwent median sternotomy and pericardiotomy followed by a standardized 2-hour protocol of forced warm air desiccation and abrasion of the pericardial and epicardial surfaces. Group 1 (n = 6) served as untreated control animals. Group 2 (n = 6) received topical administration of 0.4% hyaluronic acid in phosphate-buffered saline solution at the time of pericardiotomy, at 20-minute intervals during the desiccation/abrasion protocol, and at pericardial closure. The total test dose was less than 1% of the circulating blood volume. Group 3 (n = 6) served as a vehicle control, receiving phosphate-buffered saline solution as a topical agent in a fashion identical to that used in group 2. At resternotomy 8 weeks after the initial operation, the intrapericardial adhesions were graded on a 0 to 4 severity scale at seven different areas covering the ventricular, atrial, and great vessel surfaces. In both the untreated control (group 1, mean score 3.2 +/- 0.4) and vehicle control (group 3, mean score 3.3 +/- 0.2) animals, dense adhesions were encountered. In contrast, animals treated with the hyaluronic acid solution (group 2, mean score 0.8 +/- 0.3) characteristically had no adhesions or filmy, transparent adhesions graded significantly less severe than either the untreated control (group 2 versus group 1, p < 0.001) or vehicle control (group 2 versus group 3, p < 0.001) animals. In separate experiments, six baboons were infused with 0.4% hyaluronic acid in phosphate-buffered saline solution in volumes equivalent to 2.5%, 5%, and 10% of the measured circulating blood volume. The 2.5% and 5% infusions had no effect on the parameters measured; infusion of the 10% volume produced transient hemodynamic, coagulation, and gas exchange abnormalities. Hyaluronic acid solutions are efficacious in the prevention of pericardial adhesions in this model, and they appear safe in doses five times the amount needed to prevent adhesions. Further studies investigating the mechanism by which these solutions prevent adhesions, their optimal dose and method of application, and documentation of their safe use in humans are warranted. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,CARDIAC SURG UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BOSTON UNIV,SCH MED,USN,BLOOD RES LAB,BOSTON,MA 02118. NR 38 TC 40 Z9 41 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUN PY 1994 VL 107 IS 6 BP 1481 EP 1488 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA NQ769 UT WOS:A1994NQ76900018 PM 8196393 ER PT J AU WILLETT, CG ZIETMAN, AL SHIPLEY, WU COEN, JJ AF WILLETT, CG ZIETMAN, AL SHIPLEY, WU COEN, JJ TI THE EFFECT OF PELVIC RADIATION-THERAPY ON SERUM LEVELS OF PROSTATE-SPECIFIC ANTIGEN SO JOURNAL OF UROLOGY LA English DT Article DE PROSTATIC NEOPLASMS; ANTIGENS, NEOPLASM; RADIOTHERAPY ID RADICAL PROSTATECTOMY; CANCER; ADENOCARCINOMA; CHEMOTHERAPY; RADIOTHERAPY; CARCINOMA; TUMORS AB To determine the effect of prostatic irradiation on the production of prostate specific antigen (PSA), serum PSA levels were measured in 36 men who received pelvic irradiation (45 to 65 Gy.) for nonprostatic malignancies, and compared with those of a control group of 79 men of comparable age without prostate cancer or prior pelvic irradiation identified from the records of the Massachusetts General Hospital internal physicians. The median PSA level was lower in the irradiated group than in the control group (0.65 versus 1.1 ng./ml.). Of the irradiated patients 47% had undetectable PSA levels versus 20% of the controls (p = 0.004, Fisher's exact test). A group of 27 prostate cancer patients who received up to 68 Gy. 8 to 16 years (median 10 years) previously and who remained clinically disease-free were also studied. The median PSA level was less than 0.5 ng./ml. The proportion of patients with undetectable PSA levels was significantly higher than that of the controls (p <0.001) but it was not significantly different from those irradiated for other pelvic cancers. Of those patients 67% had an undetectable PSA level and 78% had a level of less than 1 ng./ml. Our study suggests that radiation therapy results in a permanent decrease in PSA production by the prostate gland and that patients whose PSA values do not reach less than 1 ng./ml. following radical radiation therapy for prostate cancer are unlikely to be long-term clinical disease-free survivors. RP WILLETT, CG (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 18 TC 46 Z9 47 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 JUN PY 1994 VL 151 IS 6 BP 1579 EP 1581 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA NL946 UT WOS:A1994NL94600024 PM 7514692 ER PT J AU KAUFMAN, JA EDELSTEIN, RA AF KAUFMAN, JA EDELSTEIN, RA TI ARTERIOCALICEAL FISTULA FROM PROLONGED NEPHROSTOMY TUBE DRAINAGE SO JOURNAL OF UROLOGY LA English DT Note DE CATHETERS, INDWELLING; NEPHROSTOMY, PERCUTANEOUS; HEMORRHAGE ID PERCUTANEOUS NEPHROSTOMY; URETEROARTERIAL FISTULA AB We report a case of an arteriocaliceal fistula that occurred after 21 months of continuous nephrostomy drainage. Hemorrhage was successfully controlled with selective angiography and embolization. Although unusual, arterial injury should be considered when patients with indwelling nephrostomy tubes present with new onset of bleeding. C1 BOSTON UNIV,MED CTR,DEPT UROL,BOSTON,MA. RP KAUFMAN, JA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,32 FRUIT ST,BOSTON,MA 02114, USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1994 VL 151 IS 6 BP 1616 EP 1618 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA NL946 UT WOS:A1994NL94600036 PM 8189577 ER PT J AU GOH, M KANTOFF, P KAVOUSSI, LR AF GOH, M KANTOFF, P KAVOUSSI, LR TI RETROPERITONEAL LYMPHOCELE FORMATION AFTER SELECTIVE LAPAROSCOPIC RETROPERITONEAL LYMPH-NODE SAMPLING SO JOURNAL OF UROLOGY LA English DT Note DE LYMPHOCELE; PERITONEOSCOPY; NEOPLASM STAGING ID CELL TESTIS TUMORS; PELVIC LYMPHADENECTOMY; COMPLICATIONS; DISSECTION; MANAGEMENT; CARCINOMA; CANCER AB Laparoscopic retroperitoneal lymph node sampling is being evaluated at several institutions as a minimally invasive alternative to evaluate pathologically retroperitoneal lymph nodes in cases of clinical stage A testis tumor. We report on the development of a symptomatic lymphocele after selective laparoscopic retroperitoneal lymph node sampling. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. RP GOH, M (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DIV UROL SURG,BOSTON,MA 02115, USA. NR 28 TC 3 Z9 3 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 JUN PY 1994 VL 151 IS 6 BP 1626 EP 1628 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA NL946 UT WOS:A1994NL94600039 PM 8189580 ER PT J AU PAROLIN, C DORFMAN, T PALU, G GOTTLINGER, H SODROSKI, J AF PAROLIN, C DORFMAN, T PALU, G GOTTLINGER, H SODROSKI, J TI ANALYSIS IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VECTORS OF CIS-ACTING SEQUENCES THAT AFFECT GENE-TRANSFER INTO HUMAN-LYMPHOCYTES SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL MESSENGER-RNA; HELPER-CELL LINE; RETROVIRAL VECTORS; PACKAGING SIGNAL; AIDS VIRUS; HTLV-III; LEUKEMIA-VIRUS; T4 MOLECULE; GAG REGION; EXPRESSION AB Human immunodeficiency virus type 1 (HIV-1) can be used to generate recombinant viral vectors far delivery of heterologous genes to human CD4-positive lymphocytes. To define the cis-acting sequences required for efficient gene transfer, a number of HIV-1 vectors containing a previously identified packaging signal, long terminal repeats. and additional gag, pol, and env viral sequences were designed. By providing the viral proteins in trans, recombinant viruses were generated and analyzed for their abilities to transfer genes into human T lymphocytes. Inclusion of up to 653 nucleotides derived from the 5' end of the gag gene in the vector improved the efficiency of gene transfer, but inclusion of additional gag or pol sequences did net further improve this efficiency. The increased efficiency of gene transfer associated with the inclusion of 5' gag sequences in the vector arose, at least in part, from an increase in the packaging of vector RNA. The presence of the Rev-responsive element (RRE) increased the efficiency of transfer of vectors containing significant lengths of gag sequence, as expected from the Rev requirement for nucleus-to-cytoplasm transport of unspliced vector RNA containing intact packaging signals. However, the presence of a RRE did not affect the transfer efficiency of smaller vectors lacking significant lengths of gag sequences, arguing against a specific role for the RRE in packaging or vector transfer. These results contribute to an understanding of the minimal cis-acting sequences that operate in the contest of HIV-1 vectors for delivering genes into human lymphocytes. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. UNIV PADUA,INST MICROBIOL,I-35121 PADUA,ITALY. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI27702, AI34267] NR 62 TC 113 Z9 114 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 JUN PY 1994 VL 68 IS 6 BP 3888 EP 3895 PG 8 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900048 PM 7910642 ER PT J AU MARSHALL, WL MITTLER, ES AVERY, P LAWRENCE, JP FINBERG, RW AF MARSHALL, WL MITTLER, ES AVERY, P LAWRENCE, JP FINBERG, RW TI GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHORED CD4 SUPPORTS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION, BUT NOT CYTOPATHIC EFFECT, IN T-CELL TRANSFECTANTS SO JOURNAL OF VIROLOGY LA English DT Note ID PROTEIN-TYROSINE KINASE; SYNCYTIUM FORMATION; ENVELOPE GLYCOPROTEIN; HTLV-III/LAV; RECEPTOR; INFECTION; EXPRESSION; ANTIGEN; AIDS; HIV AB Despite equivalent p24 antigen production, HSB-2 T cells ex-pressing glycosylphosphatidylinositol (GPi)linked CD4 were productively infected without cell death or syncytium formation, unlike HSB-2 transfectants expressing wild-type CD4 (wtCD4). HSB-2 transfectants dually expressing wtCD4 and GPi-linked CD4 formed syncytia and died. Thus, wtCD4 expression is critical for human immunodeficiency virus cytopathic effect in HSB-2 transfectants. C1 DANA FARBER CANC INST,DIV INFECT DIS,BOSTON,MA 02115. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI07386-04, AI01078-01, AI28961-05] NR 37 TC 5 Z9 5 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 JUN PY 1994 VL 68 IS 6 BP 4039 EP 4042 PG 4 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900067 PM 8189539 ER PT J AU SUNDAY, ME WILLETT, CG PATIDAR, K GRAHAM, SA AF SUNDAY, ME WILLETT, CG PATIDAR, K GRAHAM, SA TI MODULATION OF ONCOGENE AND TUMOR-SUPPRESSOR GENE-EXPRESSION IN A HAMSTER MODEL OF CHRONIC LUNG INJURY WITH VARYING DEGREES OF PULMONARY NEUROENDOCRINE CELL HYPERPLASIA SO LABORATORY INVESTIGATION LA English DT Article DE MYC; RETINOBLASTOMA; GENE; CALCITONIN; GENE-RELATED PEPTIDE; POLYMERASE CHAIN REACTION; PROLIFERATING CELL NUCLEAR ANTIGEN ID GASTRIN-RELEASING PEPTIDE; BOMBESIN-LIKE IMMUNOREACTIVITY; C-MYC GENES; GROWTH-FACTORS; NEUROEPITHELIAL BODIES; AIRWAY EPITHELIUM; ENDOCRINE-CELLS; FETAL LUNG; N-MYC; K-RAS AB BACKGROUND: Intense pulmonary neuroendocrine cell (PNEC) hyperplasia occurs during preneoplastic lung injury in hamsters treated with diethylnitrosamine (DEN) plus hyperoxia. Alterations in oncogene and tumor suppressor gene expression during this process have not been explored. EXPERIMENTAL DESIGN: Our goals were: (a) to analyze expression of genes potentially involved in growth and differentiation of PNECs and/or nonneuroendocrine pulmonary epithelial cells (non-PNECs) in hamsters treated for up to 20 weeks with hyperoxia and DEN or the major tobacco-derived nitrosamine, 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK); and (b) as a corollary, to determine which cells were most mitotically active by immunostaining for c-myc and proliferating cell nuclear antigen. RESULTS: Immunohistochemical analyses demonstrated intense PNEC hyperplasia after treatment with either DEN/O-2 or NNK/O-2. Whereas DEN/O-2-induced PNEC hyperplasia spontaneously regressed, NNK/O-2-induced PNEC hyperplasia continued to increase up to 20 weeks. Rb transcripts were decreased similarly in lungs from all treatment groups (NNK/O-2 = DEN/O-2 = DEN alone) in spite of large differences in PNEC hyperplasia between these groups. c-myc was overexpressed in lungs from animals treated with NNK/O-2, DEN/O-2 and DEN alone, in which c-myc protein immunostaining occurred predominantly in non-PNECs. Proliferating cell nuclear antigen immunostaining confirmed that non-PNECs were most mitotically active. CONCLUSIONS: These data indicate that PNEC hyperplasia is primarily due to PNEC differentiation, suggesting that this model is ideal for studying mechanisms of neuroendocrine differentiation. Paracrine effects of PNEC-derived growth factors may then contribute to dysregulation of non-PNEC growth preceding the ultimate development of non-neuroendocrine lung tumors in nitrosamine-treated hamsters. C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP SUNDAY, ME (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [R01 HL44984] NR 84 TC 32 Z9 32 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 1994 VL 70 IS 6 BP 875 EP 888 PG 14 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA NU620 UT WOS:A1994NU62000012 PM 8015292 ER PT J AU PAIETTA, E ANDERSEN, J RACEVSKIS, J GALLAGHER, R BENNETT, J YUNIS, J CASSELETH, P WIERNIK, PH AF PAIETTA, E ANDERSEN, J RACEVSKIS, J GALLAGHER, R BENNETT, J YUNIS, J CASSELETH, P WIERNIK, PH TI SIGNIFICANTLY LOWER P-GLYCOPROTEIN EXPRESSION IN ACUTE PROMYELOCYTIC LEUKEMIA THAN IN OTHER TYPES OF ACUTE MYELOID-LEUKEMIA - IMMUNOLOGICAL, MOLECULAR AND FUNCTIONAL ANALYSES SO LEUKEMIA LA English DT Article ID MDR1 GENE-EXPRESSION; BONE-MARROW CELLS; MULTIDRUG-RESISTANCE; CLINICAL-SIGNIFICANCE; MONOCLONAL-ANTIBODY; PERIPHERAL-BLOOD; PHENOTYPE; MYELODYSPLASIA; CYTOTOXICITY; DIAGNOSIS AB Expression of P-glycoprotein (Pgp), the product of the multidrug resistance (MDR1) gene, detected by flow cytometric analysis of the binding of antibody 4E3.16, was found on significantly fewer leukemic cells in 35 adult patients with de novo acute promyelocytic leukemia (APL) (mean 14.8%, median 7%) than in 184 patients with non-APL acute myeloid leukemia (AML) at diagnosis (mean 28.3%, median 18%) (p = 0.0038). APL was diagnosed based on morphology, the detection of t(15;17) and of the chimeric fusion transcript PML/RAR alpha by PCR. To further substantiate low MDR1 expression in APL, we studied cells from 11 APL patients at the molecular and functional level in comparison to 48 non-APL cases. The diagnosis of APL was associated with the absence of Pgp function by the rhodamine efflux assay (p=0.0001). Furthermore, MDR1-specific transcript levels, determined by quantitative PCR with two distinct sets of primers, were significantly lower in mononuclear cells from the APL than the other AML cases (p=0.013). The frequency of leukemic cells positive for CD34, an antigen presumably associated with Pgp expression in AML, was significantly lower in APL than other AMLs (p = 0.0001). In contrast to non-APL leukemias, those few cases of CD34 strongly positive APL neither expressed Pgp nor contained significant MDR1 transcript levels. Low expression of Pgp by APL cells may provide the biologic basis for the high sensitivity of this leukemia subtype to chemotherapeutic agents in vivo. C1 ALBERT EINSTEIN CANC CTR,BRONX,NY. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA. UNIV ROCHESTER,DEPT PHYSIOL,DIV MED ONCOL,ROCHESTER,NY 14642. THOMAS JEFFERSON UNIV,DIV CANC BIOL,PHILADELPHIA,PA 19107. UNIV MIAMI,DEPT HEMATOL ONCOL,MIAMI,FL 33152. EASTERN COOPERAT ONCOL GRP,DENVER,CO. RP PAIETTA, E (reprint author), MONTEFIORE MED CTR,DEPT ONCOL,111 E 210TH ST,BRONX,NY 10467, USA. FU NCI NIH HHS [NCI CA21115, NCI CA23318, NCI CA14958] NR 33 TC 84 Z9 85 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 1994 VL 8 IS 6 BP 968 EP 973 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA NU502 UT WOS:A1994NU50200011 PM 7516029 ER PT J AU MIKAEL, N BOGUNIEWICZ, M MANAKATA, Y SASAKI, T BOREL, H BOREL, Y AF MIKAEL, N BOGUNIEWICZ, M MANAKATA, Y SASAKI, T BOREL, H BOREL, Y TI CONJUGATES OF DSDNA LINKED TO HUMAN GAMMA-GLOBULIN INHIBIT ANTI-DSDNA ANTIBODIES IN-VITRO SO LUPUS LA English DT Article DE SYSTEMIC LUPUS ERYTHEMATOSUS; ANTI-DSDNA ANTIBODY; DSDNA HUMAN GAMMA-GLOBULIN CONJUGATES ID SYSTEMIC LUPUS-ERYTHEMATOSUS; INTRAVENOUS GAMMA-GLOBULIN; DNA ANTIBODY; NATIVE DNA; CIRCULATING DNA; AUTOANTIBODIES; IMMUNOGLOBULIN; ANTICOAGULANT; FRAGMENTS AB Previous studies have shown that both nucleosides and oligonucleotides linked to isologous gammaglobulin suppress anti-nucleic acid antibody production both in vivo and in vitro. The aim of this study was to determine whether one can make a DNA-human gammaglobulin (HGG) conjugate which can inhibit anti-double stranded DNA (dsDNA) antibodies obtained from a heterogeneous population of systemic lupus eruthematosus (SLE) sera. To do so, we constructed conjugates of sonicated dsDNA fragments of 100-400 base pairs covalently linked to HGG with varying degrees of substitution of DNA:HGG. An ELISA inhibition assay was used to determine which conjugate best inhibits the binding of anti-dsDNA antibodies. Conjugate 2, prepared with monomeric HGG (150kD) with a high degree of substitution (3.72 DNA:HGG) inhibited the binding of anti-dsDNA antibodies from 27 of 31 SLE sera. In addition, this conjugate inhibited the spontaneous formation of anti-dsDNA in vitro by cultured lymphoid cells from selected SLE patients. Together, this data suggests that a 'generic' tolerogen may provide an antigen specific therapy for SLE. C1 CHILDRENS HOSP MED CTR,DIV IMMUNOL,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. FAULKNER HOSP,DEPT MED,BOSTON,MA 02130. TOHOKU UNIV,SCH MED,DEPT INTERNAL MED 2,SENDAI,MIYAGI 980,JAPAN. FU NIAMS NIH HHS [AR 36830] NR 28 TC 2 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0961-2033 J9 LUPUS JI Lupus PD JUN PY 1994 VL 3 IS 3 BP 173 EP 179 DI 10.1177/096120339400300308 PG 7 WC Rheumatology SC Rheumatology GA PC252 UT WOS:A1994PC25200008 PM 7524918 ER PT J AU WEISSKOFF, RM ZUO, CS BOXERMAN, JL ROSEN, BR AF WEISSKOFF, RM ZUO, CS BOXERMAN, JL ROSEN, BR TI MICROSCOPIC SUSCEPTIBILITY VARIATION AND TRANSVERSE RELAXATION - THEORY AND EXPERIMENT SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE CONTRAST AGENTS; SUSCEPTIBILITY; T-2-ASTERISK; MONTE CARLO MODELING ID CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; POSITRON EMISSION TOMOGRAPHY; HUMAN-BRAIN-FUNCTION; COMPUTED-TOMOGRAPHY; CONTRAST AGENTS; SPIN RELAXATION; DIFFUSION; MRI; FIELDS AB Microscopic susceptibility variations invariably increase apparent transverse relaxation rates. In this paper, we present comparisons between Monte Carlo simulations and experiments with polystyrene microspheres to demonstrate that this enhanced relaxation can be explained quantitatively for both spin echo and gradient echo imaging experiments. The spheres used (1 to 30 mu), and degree of susceptibility variation (caused by 0-12 mM Dy-DTPA) covered a wide range of biologically relevant compartment sizes and contrast agent concentrations. These results show that several regimes of behavior exist, and that contrast dependence is quite different in these regimes. For a given susceptibility, Delta(X), a small range of particle sizes show peak transverse relaxation. For the range of susceptibilities found in the first pass of a clinical IV contrast agent bolus, this size range is 5 to 10 mu, or roughly capillary sized compartments. In both our simulations and experiments, smaller spheres showed quadratic relaxation versus concentration curves, and larger particles showed sublinear behavior. For particles corresponding to the peak relaxivity, the relaxation-concentration curves were linear. In addition, we demonstrated that increasing the diffusion coefficient can increase, decrease, or, paradoxically, leave unaffected the apparent relaxation rate. The regime for which the diffusion coefficient is relatively unimportant corresponds to the region of peak relaxivity. By using the Bloch-Torrey equation to produce scaling rules, the specific Monte Carlo simulations were extended to more general cases. We use these scaling rules to demonstrate why we often find that susceptibility-induced relaxation rates vary approximately linearly with concentration of injected agent. C1 HARVARD UNIV,MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,BOSTON,MA. RP WEISSKOFF, RM (reprint author), MASSACHUSETTS GEN HOSP,MGH NMR CTR,DEPT RADIOBIOL,2ND FLOOR,BLDG 149,13TH ST,BOSTON,MA, USA. FU NCI NIH HHS [5P01CA48729] NR 51 TC 466 Z9 470 U1 0 U2 22 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUN PY 1994 VL 31 IS 6 BP 601 EP 610 DI 10.1002/mrm.1910310605 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NN571 UT WOS:A1994NN57100004 PM 8057812 ER PT J AU PAHLAVANI, MA RICHARDSON, A AF PAHLAVANI, MA RICHARDSON, A TI AGE-RELATED DECREASE IN THE NAIVE (OX22+) T-CELLS IN F344 RATS SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE AGING; NAIVE (OX22+) T CELLS; RAT ID LYMPHOCYTE SUBSETS; PERIPHERAL-BLOOD; IMMUNE FUNCTION; EXPRESSION; INTERLEUKIN-2; MICE; ANTIGEN; YOUNG; RESTRICTION; PATTERNS AB The frequency of the cells bearing the naive marker (OX22+) in T cells, helper, and cytotoxic/suppressor T cell subsets isolated from the spleens of young and old F344 rats were measured by flow cytometry. The percentage of naive cells in T cells decreased significantly with age and this decline occurred primarily in the helper subset. C1 UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. RP PAHLAVANI, MA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,GRECC 182,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. FU NIA NIH HHS [AG-00165, AG-01548] NR 35 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD JUN PY 1994 VL 74 IS 3 BP 171 EP 176 DI 10.1016/0047-6374(94)90088-4 PG 6 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA NV131 UT WOS:A1994NV13100003 PM 7934214 ER PT J AU SCHIFF, I UTIAN, W AF SCHIFF, I UTIAN, W TI INTRODUCTION TO PRACTICAL PERSPECTIVES SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material C1 MASSACHUSETTS GEN HOSP,DIV WOMENS CARE,BOSTON,MA 02114. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH. UNIV CLEVELAND HOSP,DEPT OBSTET & GYNECOL,CLEVELAND,OH 44106. RP SCHIFF, I (reprint author), HARVARD UNIV,SCH MED,BOSTON,MA, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SUM PY 1994 VL 1 IS 2 BP 65 EP 65 DI 10.1097/00042192-199400120-00001 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA QB025 UT WOS:A1994QB02500001 ER PT J AU BARNHILL, RL CASTRESANA, JS RUBIO, MP MARTIN, MT IDOATE, M VAZQUEZ, JJ THOR, AD AF BARNHILL, RL CASTRESANA, JS RUBIO, MP MARTIN, MT IDOATE, M VAZQUEZ, JJ THOR, AD TI P53 EXPRESSION IN CUTANEOUS MALIGNANT-MELANOMA - AN IMMUNOHISTOCHEMICAL STUDY OF 87 CASES OF PRIMARY, RECURRENT, AND METASTATIC MELANOMA SO MODERN PATHOLOGY LA English DT Article DE MALIGNANT MELANOMA; P53 GENE; IMMUNOPATHOLOGY; SKIN ID TUMOR SUPPRESSOR GENE; PROTEIN; CANCERS AB Recent studies on the role of the p53 gene in human melanoma have largely been contradictory. To further assess p53 expression in melanoma, we have studied p53 immunoreactivity in 87 cases of primary, recurrent, and metastatic melanoma. Routine immunostaining was performed on paraffin sections with the monoclonal antibody PAb1801 and a streptavidin-biotin method. All specimens were blindly and independently assessed by two observers for number of melanoma cells with granular nuclear staining. Seven melanomas (8%) exhibited from 1 to 50% positive cells and another eight cases (9%) showed p53 immunoreactivity in <1% of cells. All of the melanomas found to be positive for p53 with one exception (<1.50 mm) were either thicker than 1.50 mm, recurrent, or metastatic. We conclude that these findings provide little evidence for significant p53 alteration in the initiation and development of melanoma. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL DERMATOPATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,MOLEC NEUROONCOL LAB,BOSTON,MA. MASSACHUSETTS GEN HOSP,NEUROSURG SERV,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. CRUCES HOSP,DEPT PATHOL,BARACALDO,SPAIN. UNIV NAVARRA,DEPT HISTOL & ANAT PATHOL,E-31080 PAMPLONA,SPAIN. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. RI Rubio, Mari-Paz/K-4364-2014; OI Rubio, Mari-Paz/0000-0003-3963-5903; Castresana, Javier S./0000-0002-2373-482X NR 11 TC 18 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 JUN PY 1994 VL 7 IS 5 BP 533 EP 535 PG 3 WC Pathology SC Pathology GA NW310 UT WOS:A1994NW31000004 PM 7937717 ER PT J AU FUDGE, K WANG, CY STEARNS, ME AF FUDGE, K WANG, CY STEARNS, ME TI IMMUNOHISTOCHEMISTRY ANALYSIS OF PLATELET-DERIVED GROWTH FACTOR-A AND FACTOR-B CHAINS AND PLATELET-DERIVED GROWTH-FACTOR-ALPHA AND BETA-RECEPTOR EXPRESSION IN BENIGN PROSTATIC HYPERPLASIAS AND GLEASON-GRADED HUMAN PROSTATE ADENOCARCINOMAS SO MODERN PATHOLOGY LA English DT Article DE ADENOCARCINOMA; PDGF A/B; PDGF RECEPTORS; PROSTATE CANCER; IMMUNOLABELING; GLEASON GRADING ID SIMIAN SARCOMA-VIRUS; FACTOR A-CHAIN; PDGF-A; HUMAN-FIBROBLASTS; TRANSFORMATION; HOMODIMERS; CELLS; GENES AB The purpose of this study was to determine whether changes in the expression of platelet-derived growth factor (PDGF) and its receptors were associated with prostate cancer. Peroxidase-anti-peroxidase-immunoperoxidase labeling was used to detect the A and B chains and alpha and beta receptors of PDGF in 5 benign prostatic hyperplasias and 13 human prostate adenocarcinomas (Gleason grades 2 to 9). In all 5 benign prostatic hyperplasias, none of the PDGF antibodies (even at high titers, 1:50 dilutions) labeled the epithelial or the stromal cells. In adenocarcinomas, the A chain and alpha receptor antibodies labeled both epithelial and stromal cells. The intensity of the staining was relatively high in low Gleason grade (<6) and low in high Gleason grade (>7) tissue; however, the B chain and beta receptor antibodies failed to label either epithelial or stromal cells in any of the 13 adenocarcinomas. The data suggest that PDGF A and alpha receptor genes may be preferentially turned on in epithelial and stromal prostate tumor cells. C1 MED COLL PENN,DEPT PATHOL,PHILADELPHIA,PA 19129. VET ADM MED CTR,PHILADELPHIA,PA 19104. HARVARD UNIV,SCH MED,DIV CELLULAR & MOLEC BIOL,BOSTON,MA. DANA FARBER CANC INST,BOSTON,MA. FU NCI NIH HHS [CA57180] NR 24 TC 100 Z9 105 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 JUN PY 1994 VL 7 IS 5 BP 549 EP 554 PG 6 WC Pathology SC Pathology GA NW310 UT WOS:A1994NW31000008 PM 7524068 ER PT J AU MYERS, MG WANG, LM SUN, XJ ZHANG, YT YENUSH, L SCHLESSINGER, J PIERCE, JH WHITE, MF AF MYERS, MG WANG, LM SUN, XJ ZHANG, YT YENUSH, L SCHLESSINGER, J PIERCE, JH WHITE, MF TI ROLE OF IRS-1-GRB-2 COMPLEXES IN INSULIN SIGNALING SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; RECEPTOR TYROSINE KINASES; PHOSPHATIDYLINOSITOL 3'-KINASE; NUCLEOTIDE EXCHANGE; HEMATOPOIETIC-CELLS; PROTEIN-KINASES; SH3 DOMAINS; RAS; IRS-1; GRB2 AB GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21(ras) during growth factor signaling. During insulin stimulation, GRB-2 binds to the phosphorylated Y-895 VNI motif of IRS-1. Substitution of Tyr-845 with phenylalanine (IRS-1(F-895)) prevented the IRS-1-GRB-2 association in vivo and in vitro. The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. Coexpression of IRS-1 or IRS-1(F-895) with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of She and activation of p21(ras) and mitogen-activated protein (MAP) kinase. The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21(ras) and MAP kinase activation in IRS-1-deficient 32-D cells. Interestingly, IRS-1, but not IRS-1(F-895), enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. Our results suggest that the Shc-GRB-2 complex and the activation of p21(ras)-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. NYU,SCH MED,NEW YORK,NY 10016. NIH,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK 33201, DK 38712, DK 43808] NR 48 TC 180 Z9 182 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1994 VL 14 IS 6 BP 3577 EP 3587 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NM741 UT WOS:A1994NM74100005 PM 8196603 ER PT J AU STAUNTON, JE WEAVER, DT AF STAUNTON, JE WEAVER, DT TI SCID CELLS EFFICIENTLY INTEGRATE HAIRPIN AND LINEAR DNA SUBSTRATES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID COMBINED IMMUNE-DEFICIENCY; V(D)J RECOMBINATION; HOMOLOGOUS RECOMBINATION; IONIZING-RADIATION; GENE REARRANGEMENT; MOUSE THYMOCYTES; MAMMALIAN-CELLS; CODING SEGMENTS; STRAND BREAKS; MUTATION AB The scid mouse mutation affects V(D)J rearrangement and double-strand break repair. scid V(D)J rearrangement is characterized by defective coding joint formation which prevents the development of mature B and T cells. Hairpin DNA has been implicated in the formation of V(D)J coding joints. We found scid cells to be proficient in hairpin processing in the context of DNA integration. In addition, we found that the scid defect did not impair integration of linear DNA via nonhomologous recombination. Therefore, hairpin processing and integration of DNA into the genome are distinct from hypersensitivity to ionizing radiation and the defect in V(D)J recombination. C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. FU NCI NIH HHS [CA54326] NR 29 TC 17 Z9 17 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 JUN PY 1994 VL 14 IS 6 BP 3876 EP 3883 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NM741 UT WOS:A1994NM74100034 PM 8196630 ER PT J AU LICHT, JD HANNAROSE, W REDDY, JC ENGLISH, MA RO, M GROSSEL, M SHAKNOVICH, R HANSEN, U AF LICHT, JD HANNAROSE, W REDDY, JC ENGLISH, MA RO, M GROSSEL, M SHAKNOVICH, R HANSEN, U TI MAPPING AND MUTAGENESIS OF THE AMINO-TERMINAL TRANSCRIPTIONAL REPRESSION DOMAIN OF THE DROSOPHILA KRUPPEL PROTEIN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EVEN-SKIPPED PROTEIN; DNA-BINDING PROTEIN; TUMOR GENE-PRODUCT; RNA POLYMERASE-II; WILMS-TUMOR; FUNCTIONAL DOMAINS; SEGMENTATION GENE; MAMMALIAN-CELLS; GAP GENES; EXPRESSION AB We previously demonstrated that the Drosophila Kruppel protein is a transcriptional repressor with separable DNA-binding and transcriptional repression activities. In this study, the minimal amino (N)-terminal repression region of the Kruppel protein was defined by transferring regions of the Kruppel protein to a heterologous DNA-binding protein, the lacI protein. Fusion of a predicted alpha-helical region from amino acids 62 to 92 in the N terminus of the Kruppel protein was sufficient to transfer repression activity. This putative alpha-helix has several hydrophobic surfaces, as well as a glutamine-rich surface. Mutants containing multiple amino acid substitutions of the glutamine residues demonstrated that this putative or-helical region is essential for repression activity of a Kruppel protein containing the entire N-terminal and DNA-binding regions. Furthermore, one point mutant with only a single glutamine on this surface altered to lysine abolished the ability of the Kruppel protein to repress, indicating the importance of the amino acid at residue 86 for repression. The N terminus also contained an adjacent activation region localized between amino acids 86 and 117. Finally, in accordance with predictions from primary amino acid sequence similarity, a repression region from the Drosophila even-skipped protein, which was six times more potent than that of the Kruppel protein in the mammalian cells, was characterized. This segment included a hydrophobic stretch of 11 consecutive alanine residues and a proline-rich region. C1 DANA FARBER CANC INST,EUKARYOT TRANSCRIPT LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. CUNY MT SINAI SCH MED,BROOKDALE CTR MOLEC BIOL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT MED,NEW YORK,NY 10029. FU NCI NIH HHS [T32-CA09361, K11-CA01272]; NCRR NIH HHS [S07-RR05526] NR 72 TC 63 Z9 63 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 JUN PY 1994 VL 14 IS 6 BP 4057 EP 4066 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NM741 UT WOS:A1994NM74100051 PM 8196644 ER PT J AU WECHSLER, DS PAPOULAS, O DANG, CV KINGSTON, RE AF WECHSLER, DS PAPOULAS, O DANG, CV KINGSTON, RE TI DIFFERENTIAL BINDING OF C-MYC AND MAX TO NUCLEOSOMAL DNA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HELIX-LOOP-HELIX; TRANSCRIPTION FACTOR ACCESS; LAMBDA-PHAGE REPRESSOR; TUMOR VIRUS PROMOTER; LEUCINE ZIPPER; OPPOSITE ORIENTATIONS; HISTONE ACETYLATION; RNA-POLYMERASE; BEND DNA; DOMAINS AB The ability of a transcription factor to function in vivo must be determined in part by its ability to bind to its recognition site in chromatin. We have used Max and derivatives of c-Myc to characterize the effect of changes of dimerization partner on binding to nucleosomal DNA templates. We find that homo- and heterodimeric complexes of these proteins bind to the CACGTG sequence in free DNA,vith similar affinities. Although Max homodimers bind to nucleosomes, truncated c-Myc homodimers do not. Surprisingly, modifying the c-Myc dimerization interface or changing its dimerization partner to Max enables nucleosomal DNA binding. Thus, changes in dimer structure or dimerization efficiency can have significant effects on nucleosome binding that are not predicted from their affinity for free DNA. We conclude that domains other than the basic region per se influence the ability of a transcription factor to bind to nucleosomal DNA and that changes of dimerization partner can directly affect the ability of a factor to occupy nucleosomal binding sites. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,DIV HEMATOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV HEMATOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,DIV HEMATOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21205. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. FU NCI NIH HHS [CA57341-01]; NIGMS NIH HHS [GM48405] NR 58 TC 42 Z9 43 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1994 VL 14 IS 6 BP 4097 EP 4107 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NM741 UT WOS:A1994NM74100055 PM 8196648 ER PT J AU CROS, D TRIGGS, WJ AF CROS, D TRIGGS, WJ TI THERE ARE NO NEUROPHYSIOLOGIC FEATURES CHARACTERISTIC OF AXONAL GUILLAIN-BARRE-SYNDROME SO MUSCLE & NERVE LA English DT Note ID EXPERIMENTAL ALLERGIC NEURITIS; CONDUCTION BLOCK; CAMPYLOBACTER-JEJUNI; POLYNEUROPATHY; DEMYELINATION; DEGENERATION; ANTIBODIES; FORM; NEUROPATHY; DISORDERS AB Classical views hold Guillain-Barre Syndrome (GBS) as a primary inflammatory-demyelinating neuropathy in which secondary axonal degeneration may occur, particularly when inflammatory lesions are severe. Feasby and colleagues proposed that primary axonal degeneration can also cause GBS characterized by inexcitable motor nerves and poor outcome. This hypothesis rests largely on the results of a single autopsy in which no inflammation or demyelination were found. Using an illustrative case report confirming earlier studies, we point out that inexcitable motor nerves (or low amplitude compound muscle action potentials [CMAPs]) are of ambiguous significance and may reflect distal demyelination, causing conduction block between distal stimulation sites and target muscles, a pattern not uncommon in GBS. Recovery from such lesions may occur within weeks with restoration of CMAP amplitudes. The recognition of a yet unproven axonal variant of GBS cannot be based solely on documentation of inexcitable motor nerves in the context of rapidly developing weakness, (C) 1994 John Wiley & Sons, Inc. RP CROS, D (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,EMG UNIT BIGELOW 12,BOSTON,MA 02114, USA. NR 27 TC 31 Z9 31 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD JUN PY 1994 VL 17 IS 6 BP 675 EP 677 DI 10.1002/mus.880170617 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NN055 UT WOS:A1994NN05500016 PM 8196711 ER PT J AU CORDER, EH SAUNDERS, AM RISCH, NJ STRITTMATTER, WJ SCHMECHEL, DE GASKELL, PC RIMMLER, JB LOCKE, PA CONNEALLY, PM SCHMADER, KE SMALL, GW ROSES, AD HAINES, JL PERICAKVANCE, MA AF CORDER, EH SAUNDERS, AM RISCH, NJ STRITTMATTER, WJ SCHMECHEL, DE GASKELL, PC RIMMLER, JB LOCKE, PA CONNEALLY, PM SCHMADER, KE SMALL, GW ROSES, AD HAINES, JL PERICAKVANCE, MA TI PROTECTIVE EFFECT OF APOLIPOPROTEIN-E TYPE-2 ALLELE FOR LATE-ONSET ALZHEIMER-DISEASE SO NATURE GENETICS LA English DT Article ID GENETIC-LINKAGE; RISK; CHROMOSOME-19; RELATIVES; DEMENTIA; LOCUS; DIAGNOSIS; FAMILIES; PROTEIN; AGE AB Gene dosage of the apolipoprotein E (APOE) epsilon 4 allele is a major risk factor for familiar Alzheimer disease (AD) of late onset (after age 60). Here we studied a large series of 115 AD case subjects and 243 controls as well as 150 affected and 197 unaffected members of 66 AD families. Our data demonstrate a protective effect of the epsilon 2 allele, in addition to the dose effect of the epsilon 4 allele in sporadic AD. Although a substantial proportion (65%) of AD is attributable to the presence of epsilon 4 alleles, risk of AD is lowest in subjects with the epsilon 2/epsilon 3 genotype, with an additional 23% of AD attributable to the absence of an epsilon 2 allele. The opposite actions of the epsilon 2 and epsilon 4 alleles further support the direct involvement of APOE in the pathogenesis of AD. C1 DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DIV NEUROL,DURHAM,NC 27710. DUKE UNIV,MED CTR,JOSEPH & KATHLEEN BRYAN ALZHEIMERS DIS RES CTR,DIV NEUROBIOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. YALE UNIV,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. YALE UNIV,DEPT GENET,NEW HAVEN,CT 06520. VET ADM MED CTR,GRECC DURHAM,DURHAM,NC 27704. MASSACHUSETTS GEN HOSP,MOLEC NEUROGENET UNIT,BOSTON,MA 02129. INDIANA UNIV,MED CTR,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. UNIV CALIF LOS ANGELES,CTR HLTH SCI,NEUROPSYCHIAT INST & HOSP,LOS ANGELES,CA 90024. RI Haines, Jonathan/C-3374-2012 FU NIA NIH HHS [NIA AG05128, U24 AG021886]; NINDS NIH HHS [NINDS NS26630, NINDS NS531153] NR 43 TC 1168 Z9 1192 U1 5 U2 40 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 JUN PY 1994 VL 7 IS 2 BP 180 EP 184 DI 10.1038/ng0694-180 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA NQ037 UT WOS:A1994NQ03700019 PM 7920638 ER PT J AU RIZZO, JF LESSELL, S AF RIZZO, JF LESSELL, S TI CEREBROVASCULAR ABNORMALITIES IN NEUROFIBROMATOSIS TYPE-1 SO NEUROLOGY LA English DT Editorial Material ID ARTERIAL OCCLUSIVE DISEASE; VONRECKLINGHAUSENS NEUROFIBROMATOSIS; CHILDREN; PATIENT; LESIONS C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. RP RIZZO, JF (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,243 CHARLES ST,BOSTON,MA 02114, USA. NR 30 TC 18 Z9 18 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1994 VL 44 IS 6 BP 1000 EP 1002 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA NR468 UT WOS:A1994NR46800003 PM 8208389 ER PT J AU SOBEL, NB AF SOBEL, NB TI PROGESTINS IN PREVENTIVE HORMONE-THERAPY - INCLUDING PHARMACOLOGY OF THE NEW PROGESTINS, DESOGESTREL, NORGESTIMATE AND GESTODENE - ARE THERE ADVANTAGES SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; CORONARY HEART-DISEASE; ESTRADIOL NORETHISTERONE ACETATE; DENSITY LIPOPROTEIN CHOLESTEROL; ACUTE MYOCARDIAL-INFARCTION; POSTMENOPAUSAL WOMEN; ORAL-CONTRACEPTIVES; SERUM-LIPIDS; CARDIOVASCULAR-DISEASE; BREAST-CANCER C1 MASSACHUSETTS GEN HOSP,DEPT GYNECOL,BOSTON,MA 02114. RP SOBEL, NB (reprint author), LAHEY CLIN FDN,DEPT GYNECOL,41 MALL RD,BURLINGTON,MA 01805, USA. NR 109 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD JUN PY 1994 VL 21 IS 2 BP 299 EP 319 PG 21 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NR243 UT WOS:A1994NR24300006 PM 7936546 ER PT J AU OHTANIFUJITA, N FUJITA, T TAKAHASHI, R ROBBINS, PD DRYJA, TP SAKAI, T AF OHTANIFUJITA, N FUJITA, T TAKAHASHI, R ROBBINS, PD DRYJA, TP SAKAI, T TI A SILENCER ELEMENT IN THE RETINOBLASTOMA TUMOR-SUPPRESSOR GENE SO ONCOGENE LA English DT Article ID TRANSCRIPTION FACTOR E2F; SITE-DIRECTED MUTAGENESIS; POLYMERASE CHAIN-REACTION; LARGE T-ANTIGEN; CELL-CYCLE; SUSCEPTIBILITY GENE; E2F-BINDING SITE; BINDING PROTEIN; CARCINOMA-CELLS; REPORTER GENE AB We have previously identified two positive regulatory elements in the retinoblastoma gene (RB) promoter. One is an ATF site and the other we have called a retinoblastoma binding factor 1 site. In addition, a consensus E2F site is located directly 3' to the ATF site. Here we demonstrate with gel shift assays that E2F and E2F-dependent complexes can bind in vitro to the E2F site of the RB promoter (RB-E2F site). Moreover, we demonstrate that deletion of the RB-E2F site results in stimulation of RB promoter activity in transient transfection assays in several cell lines. Specific point mutations in the E2F site that inhibit the binding of E2F and its complexes also stimulate the RB promoter activity, suggesting that a factor(s) that can bind to the RB-E2F site could be a silencer. RB promoter activity was also stimulated two- to four-fold by mutation of the E2F site in the RB-negative cell lines, J82 and HTB9. Taken together, our results show that the E2F site in the promoter of the RB tumor-suppressor gene acts as a silencer element and that the silencer effect of the E2F site is not necessarily dependent on the presence of the RB protein. C1 KYOTO PREFECTURAL UNIV MED,DEPT PREVENT MED,KAMIKYO KU,KYOTO 602,JAPAN. KYOTO UNIV,FAC MED,DEPT PATHOL 2,KYOTO 606,JAPAN. UNIV PITTSBURGH,SCH MED,DEPT MOLEC GENET & BIOCHEM,PITTSBURGH,PA 15261. HARVARD UNIV,SCH MED,MASSACHUSETTS EYE & EAR INFIRM,DEPT OPHTHALMOL,BOSTON,MA 02114. NR 55 TC 23 Z9 23 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 1994 VL 9 IS 6 BP 1703 EP 1711 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NL815 UT WOS:A1994NL81500023 PM 8183566 ER PT J AU RUBIN, PAD POPHAM, JK BILYK, JR SHORE, JW AF RUBIN, PAD POPHAM, JK BILYK, JR SHORE, JW TI COMPARISON OF FIBROVASCULAR INGROWTH INTO HYDROXYAPATITE AND POROUS POLYETHYLENE ORBITAL IMPLANTS SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article DE ENUCLEATION; IMPLANT, ORBITAL; HYDROXYAPATITE; POLYETHYLENE, POROUS; RABBIT MODEL; IMPLANT EXPOSURE AB Two porous orbital implants available for clinical use in the anophthalmic socket are hydroxyapatite (HA) and porous polyethylene (PP). We examined the rate and the extent of fibrovascular ingrowth into these implants using histopathologic criteria in a rabbit model. Thirty-two New Zealand white rabbits underwent a unilateral enucleation with placement of a 14-mm spherical orbital implant. Twelve rabbits received HA, 12 small-pore PP, and 8 large-pore PP. The implants inserted were wrapped either in autologous sclera with and without anterior fenestrations or as unwrapped spheres. The implants were harvested at 6 and 12 weeks. The extent of fibrovascular ingrowth was assessed by determining the percentage of the cross-sectional area penetrated by fibrovascular tissue. On gross inspection, 12 implants (37.5%) were found to be exposed at harvesting; however, only two were grossly infected. The highest- rate of exposure was found among the unwrapped implants. Wrapped versus unwrapped and fenestrated versus unfenestrated implants did not result in significant differences in the extent of vascularization. Hydroxyapatite implants were vascularized most rapidly. The small-pore PP implants did not become fully vascularized during the study, and yet complete vascularization was found in the large-pore PP at 12 weeks. The most intense areas of microscopic fibrovascular ingrowth were in the region where the extraocular muscles were in direct contact with the implant and at the posterior opening. Exposure of the implant was accompanied by chronic and acute inflammation. Both HA and large-pore PP spherical implants are capable of complete vascularization in this animal model. Increasing the interstitial pore size resulted in more complete vascularization of the PP. Vascularization of the implants is limited by exposure, secondary inflammation, and infection. RP RUBIN, PAD (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,CTR EYE PLAST & ORBIT,50 STANIFORD ST,BOSTON,MA 02114, USA. NR 0 TC 128 Z9 146 U1 0 U2 6 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD JUN PY 1994 VL 10 IS 2 BP 96 EP 103 DI 10.1097/00002341-199406000-00005 PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA NQ542 UT WOS:A1994NQ54200005 PM 7522048 ER PT J AU TANIISHII, N WANG, CY TANNER, A STASHENKO, P AF TANIISHII, N WANG, CY TANNER, A STASHENKO, P TI CHANGES IN ROOT-CANAL MICROBIOTA DURING THE DEVELOPMENT OF RAT PERIAPICAL LESIONS SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE RAT MICROBIOTA; ROOT CANAL; PERIAPICAL LESION ID BACTEROIDES; INFECTIONS; IDENTIFICATION AB Periapical lesions are reproducibly induced in rats by pulp exposure and infection from the oral cavity. Lesions expand rapidly between day 7 and day 15-20 (active phase), with slowed expansion thereafter. In the present study we characterized the root canal microbiota present during the active phase of lesion development in this system. The mandibular first molars of Sprague-Dawley rats were exposed on day 0. The teeth were extracted after 7 days (n = 10 animals) and 15 days (n = 10), and the microbiota present in roots was isolated and characterized. The number of colonies isolated per tooth was similar on day 7 (1.53 +/- 0.64 colony-forming units x 10(3)) and day 15 (1.49 +/- 0.37 colony-forming units x 10(3)). No colonies were isolated from unexposed control teeth. Anaerobic bacteria increased significantly between day 7 (24.3 +/- 5.7%) and day 15 (47.3 +/- 7.5%), and the proportion of gram-negative organisms increased from day 7 (24.316.1) to day 15 (46.9 +/- 6.8). The predominant bacteria included, on day 7: Streptococcus and Bacteroides species; on day 15: species of Streptococcus, Bacteroides, Prevotella, Neisseria and Peptostreptococcus. Streptococcus oralis, Streptococcus mitis, Streptococcus, Bacteroides pneumosintes and Bacteroides ureolyticus were frequently isolated at both points. Although approximately the same mean number of different species (similar to 3.5) was isolated per tooth on both day 7 and 15, the overall diversity of the isolates increased on day 15. These results demonstrate that the root canal microbiota becomes increasingly gram-negative and anaerobic with the emergence of Peptostreptococcus, Bacteroides, Prevotella and Neisseria during the period of rapid lesion expansion in this model. C1 FORSYTH DENT CTR,DEPT CYTOKINE BIOL,BOSTON,MA 02115. FORSYTH DENT CTR,DEPT MICROBIOL,BOSTON,MA 02115. FU NIDCR NIH HHS [DE-09018] NR 27 TC 46 Z9 47 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD JUN PY 1994 VL 9 IS 3 BP 129 EP 135 DI 10.1111/j.1399-302X.1994.tb00048.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA NL503 UT WOS:A1994NL50300001 PM 7936717 ER PT J AU METSON, R AF METSON, R TI METZENBAUM,MYRON,F., MD - INNOVATIVE SURGEON, CARING PHYSICIAN SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Item About an Individual C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 1994 VL 110 IS 6 BP 477 EP 481 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA NT251 UT WOS:A1994NT25100001 PM 8208559 ER PT J AU SCHUKNECHT, HF AF SCHUKNECHT, HF TI AUDITORY AND CYTOCOCHLEAR CORRELATES OF INNER-EAR DISORDERS SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID COCHLEAR AB Pure-tone threshold audiograms showing sensorineural hearing loss, when plotted on a data-based anatomic frequency scale, show a close spatial correlation with their respective cytocochleograms. Whereas most of the cochleae show pathology of several different cell types, a sufficient number show losses that involve predominantly a single cell type, which permits the following deductions: (I) focal lesions of the organ of Corti are strongly tonotopic and are responsible for those instances of abrupt pure-tone threshold losses; (2) lesions of the stria vascularis show no tonotopic organization but lead to flat pure-tone threshold losses; and (3) the principal effect of neuronal losses is a diminished capability for word recognition. There is an indeterminate group where no pathologic correlate can be identified by light microscopy. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP SCHUKNECHT, HF (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [R01 DC00079] NR 11 TC 24 Z9 26 U1 0 U2 1 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 JUN PY 1994 VL 110 IS 6 BP 530 EP 538 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA NT251 UT WOS:A1994NT25100010 PM 8208568 ER PT J AU WOLFSDORF, JI LAFFEL, LMB AF WOLFSDORF, JI LAFFEL, LMB TI DIABETES IN CHILDHOOD - PREDICTING THE FUTURE SO PEDIATRIC ANNALS LA English DT Article RP WOLFSDORF, JI (reprint author), JOSLIN DIABET CTR,DEPT PEDIAT,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0090-4481 J9 PEDIATR ANN JI Pediatr. Annu. PD JUN PY 1994 VL 23 IS 6 BP 306 EP & PG 0 WC Pediatrics SC Pediatrics GA NT201 UT WOS:A1994NT20100007 PM 8078708 ER PT J AU BRAMSON, RT BUONOMO, C BLICKMAN, JG AF BRAMSON, RT BUONOMO, C BLICKMAN, JG TI BARIUM EXTRAVASATION DISCOVERED SOME YEARS AFTER PYLOROMYOTOMY SO PEDIATRIC RADIOLOGY LA English DT Note AB Two children who had surgery for pyloric stenosis are presented. Each had an unusual density discovered on an abdominal plain radiograph taken at least a year after surgery for pyloric stenosis. Subsequent investigation showed that this density represented barium from the preoperative contrast studies that had apparently leaked into the soft tissues at the time of surgery but was not recognized at that time. This unusual complication has not been previously reported but could potentially be fairly common. Unnecessary diagnostic testing could be avoided by recognition that this complication does occur. RP BRAMSON, RT (reprint author), MASSACHUSETTS GEN HOSP,DIV PEDIAT RADIOL,BOSTON,MA 02114, USA. NR 2 TC 1 Z9 1 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 JUN PY 1994 VL 24 IS 3 BP 216 EP 217 DI 10.1007/BF02012196 PG 2 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA NU222 UT WOS:A1994NU22200021 PM 7936804 ER PT J AU JETTE, DU DOWNING, J AF JETTE, DU DOWNING, J TI HEALTH-STATUS OF INDIVIDUALS ENTERING A CARDIAC REHABILITATION PROGRAM AS MEASURED BY THE MEDICAL OUTCOMES STUDY 36-ITEM SHORT-FORM SURVEY (SF-36) SO PHYSICAL THERAPY LA English DT Article DE CARDIOVASCULAR DISEASES; HEALTH STATUS; OUTCOME AND PROCESS ASSESSMENT (HEALTH CARE); REHABILITATION ID FUNCTIONAL STATUS; VALIDITY AB Background and Purpose. The goal of health care for individuals with chronic disease is the improvement of function and well-being. Although the individual's perception of his or her quality of life may be the best indicator of achievement of this goal, measurement of self-perceived quality of life, or health status, is not a routine component of evaluation. The purposes of this article are to describe the health status of individuals upon entry into a cardiac rehabilitation program and to demonstrate the use of a comprehensive, generic health status measure in this group. Subjects. The subjects of this study were 789 men and women enrolled in one of 13 cardiac rehabilitation programs in the state of Massachusetts. Methods. As part of a large database, subjects completed a 36-item generic questionnaire, Short Form 36 (SF-36), that examines eight health concepts. Scores range from 0% to 100%, a higher score is consistent with better health status Results Mean uncontrolled scores ranged from 26.6 to 70.8. Mean scores adjusted for sex, age, and education ranged from 27.1 to 70.9 In light of previously published data using a similar 20-item scale, our results show that cardiac disease is associated with reductions in health-related quality of life. Conclusion and Discussion. Health status measurement provides information that can supplement the usual measures of impairment in patients with cardiovascular disease The findings of this study contribute to the understanding of health status of individuals who enroll in cardiac rehabilitation programs. The health status instrument used in this study has potential as a useful, practical measurement tool for use in the clinical setting [Jette DU, Downing J. Health status of individuals entering a cardiac rehabilitation program as measured by the Medical Outcomes Study 36-item Short-Form Survey (SF-36). C1 MASSACHUSETTS GEN HOSP,DIV PREVENT CARDIOL,BOSTON,MA 02114. RP JETTE, DU (reprint author), SIMMONS COLL,GRAD PROGRAM PHYS THERAPY,300 FENWAY,BOSTON,MA 02115, USA. NR 19 TC 63 Z9 63 U1 0 U2 2 PU AMER PHYS THER ASSN PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD JUN PY 1994 VL 74 IS 6 BP 521 EP 527 PG 7 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA PC957 UT WOS:A1994PC95700002 PM 8197238 ER PT J AU ZHANG, H WANG, J GOODMAN, HM AF ZHANG, H WANG, J GOODMAN, HM TI DIFFERENTIAL EXPRESSION IN ARABIDOPSIS OF LHCA2, A PSI CAB GENE SO PLANT MOLECULAR BIOLOGY LA English DT Note DE CHLOROPHYLL; LIGHT INDUCTION; NORTHERN BLOTS; PHOTOSYSTEM I; SOUTHERN BLOTS ID LIGHT-HARVESTING COMPLEX; A/B-BINDING POLYPEPTIDE; PHOTOSYSTEM-I; CHROMOSOMAL LOCATION; NUCLEOTIDE-SEQUENCE; PROTEIN GENES; HIGHER-PLANTS; THALIANA; FAMILY; 4TH AB A cDNA clone of the gene Lhca2 encoding a photosystem I (PSI) type II chlorophyll alb-binding protein was isolated from Arabidopsis thaliana. The isolation of this, the fourth PSI cab gene from Ambidopsis, confirms a previous report [1] that indicated Ambidopsis may contain all four PSI cab genes identified in other plant species. Lhca2 is a single-copy gene as are the other known Arabidopsis PSI cab genes. The patterns of developmental expression and tissue-specific regulation of Lhca2 are similar to those of other PSI and P SII cab genes, but the light induction pattern and the steady-state mRNA level of Lhca2 are distinct. This suggests that a different mechanism may be employed to regulate the expression of Lhca2. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 21 TC 8 Z9 9 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-4412 J9 PLANT MOL BIOL JI Plant Mol.Biol. PD JUN PY 1994 VL 25 IS 3 BP 551 EP 557 DI 10.1007/BF00043883 PG 7 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA PB081 UT WOS:A1994PB08100022 PM 8049378 ER PT J AU BUCKY, LP VEDDER, NB HONG, HZ EHRLICH, HP WINN, RK HARLAN, JM MAY, JW AF BUCKY, LP VEDDER, NB HONG, HZ EHRLICH, HP WINN, RK HARLAN, JM MAY, JW TI REDUCTION OF BURN INJURY BY INHIBITING CD18-MEDIATED LEUKOCYTE ADHERENCE IN RABBITS SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID MONOCLONAL-ANTIBODY; NEUTROPHIL ACTIVATION; REPERFUSION INJURY; THERMAL-INJURY; COMPLEMENT; ISCHEMIA; EXPRESSION; RECEPTORS; ADHESION; CD18 AB The progressive nature of dermal ischemia and subsequent tissue destruction within the ''zone of stasis'' is a central focus in burn research. To examine the role of neutrophils and neutrophil adherence within the zone of stasis, we utilized the monoclonal antibody (MAb) 60.3, directed to the human leukocyte adherence glycoprotein CD18 to block neutrophil adherence to endothelium and intravascular aggregation in a rabbit model of partial-thickness burn. Burns were created by applying an 80 degrees C brass template to the dorsal rabbit skin for 5 or 10 seconds. Animals treated with MAb 60.3 thirty minutes following a 5-second burn had less edema, thinner eschar, and earlier elevation of the eschar than control animals. Histologic analysis revealed an eightfold increase in live hair follicles (p < 0.05) and 43 percent greater reepithelialization at 8 days (p < 0.05) and a 15 percent reduction in burn surface area at 24 hours (p < 0.0001) in the antibody-treated group. There was no significant difference between treatment and control groups exposed to 10-second burns. We conclude that neutrophils and increased neutrophil adherence play important roles in the progressive tissue destruction within the zone of stasis in burns. Furthermore, moderate burn injury may be significantly attenuated by blocking neutrophil adherence functions with a CD18 MAb. C1 UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT SURG,DIV PLAST SURG ZA16,SEATTLE,WA 98104. HARVARD UNIV,SCH MED,DIV PLAST SURG,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA. UNIV WASHINGTON,HARBORVIEW MED CTR,DEPT MED,SEATTLE,WA 98104. FU NCRR NIH HHS [RR05432]; NIGMS NIH HHS [GM42686] NR 23 TC 45 Z9 45 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 JUN PY 1994 VL 93 IS 7 BP 1473 EP 1480 DI 10.1097/00006534-199406000-00021 PG 8 WC Surgery SC Surgery GA NV530 UT WOS:A1994NV53000021 PM 7911582 ER PT J AU FAVA, M KAJI, J AF FAVA, M KAJI, J TI CONTINUATION AND MAINTENANCE TREATMENTS OF MAJOR DEPRESSIVE DISORDER SO PSYCHIATRIC ANNALS LA English DT Article ID COGNITIVE BEHAVIOR-THERAPY; FOLLOW-UP; RECURRENT DEPRESSION; INTERPERSONAL PSYCHOTHERAPY; CLINICAL EFFICACY; DRUG-THERAPY; RELAPSE; PHARMACOTHERAPY; PREDICTORS; PHENELZINE RP FAVA, M (reprint author), MASSACHUSETTS GEN HOSP,DEPRESS RES PROGRAM,CLIN PSYCHOPHARMACOL UNIT,ACC 815,BOSTON,MA 02114, USA. NR 49 TC 41 Z9 42 U1 3 U2 5 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUN PY 1994 VL 24 IS 6 BP 281 EP 290 PG 10 WC Psychiatry SC Psychiatry GA NR046 UT WOS:A1994NR04600003 ER PT J AU POLLACK, MH OTTO, MW AF POLLACK, MH OTTO, MW TI LONG-TERM PHARMACOLOGICAL TREATMENT OF PANIC DISORDER SO PSYCHIATRIC ANNALS LA English DT Article ID BEHAVIORAL GROUP TREATMENT; FOLLOW-UP; BENZODIAZEPINE TREATMENT; MULTICENTER TRIAL; AGORAPHOBIA; ALPRAZOLAM; IMIPRAMINE; DISCONTINUATION; PLACEBO; ATTACKS C1 MASSACHUSETTS GEN HOSP,BEHAV THERAPY UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP POLLACK, MH (reprint author), MASSACHUSETTS GEN HOSP,ANXIETY DISORDERS PROGRAM,CLIN PSYCHOPHARMACOL BEHAV THERAPY UNIT,BOSTON,MA 02114, USA. NR 45 TC 17 Z9 17 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUN PY 1994 VL 24 IS 6 BP 291 EP 298 PG 8 WC Psychiatry SC Psychiatry GA NR046 UT WOS:A1994NR04600004 ER PT J AU SACHS, GS LAFER, B TRUMAN, CJ NOETH, M THIBAULT, AB AF SACHS, GS LAFER, B TRUMAN, CJ NOETH, M THIBAULT, AB TI LITHIUM MONOTHERAPY - MIRACLE, MYTH AND MISUNDERSTANDING SO PSYCHIATRIC ANNALS LA English DT Article ID RECURRENT AFFECTIVE ILLNESS; BIPOLAR AFFECTIVE-DISORDER; MANIC-DEPRESSIVE ILLNESS; DOUBLE-BLIND; FOLLOW-UP; PROPHYLAXIS; CARBONATE; UNIPOLAR; IMIPRAMINE; EFFICACY C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP SACHS, GS (reprint author), MASSACHUSETTS GEN HOSP,HARVARD BIPOLAR RES PROGRAM,WACC 815,15 PARKMAN ST,BOSTON,MA 02114, USA. RI Lafer, Beny/C-1055-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Lafer, Beny/0000-0002-6132-9999 NR 37 TC 32 Z9 32 U1 2 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUN PY 1994 VL 24 IS 6 BP 299 EP 306 PG 8 WC Psychiatry SC Psychiatry GA NR046 UT WOS:A1994NR04600005 ER PT J AU OTTO, MW GOULD, RA POLLACK, MH AF OTTO, MW GOULD, RA POLLACK, MH TI COGNITIVE-BEHAVIORAL TREATMENT OF PANIC DISORDER - CONSIDERATIONS FOR THE TREATMENT OF PATIENTS OVER THE LONG-TERM SO PSYCHIATRIC ANNALS LA English DT Article ID 2-YEAR FOLLOW-UP; BENZODIAZEPINE TREATMENT; ALPRAZOLAM; THERAPY; DISCONTINUATION; AGORAPHOBIA; PLACEBO; CLONAZEPAM; IMIPRAMINE C1 MASSACHUSETTS GEN HOSP,ANXIETY DISORDERS PROGRAM,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP OTTO, MW (reprint author), MASSACHUSETTS GEN HOSP,BEHAV THERAPY UNIT,WACC-815,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 34 TC 17 Z9 17 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUN PY 1994 VL 24 IS 6 BP 307 EP 315 PG 9 WC Psychiatry SC Psychiatry GA NR046 UT WOS:A1994NR04600006 ER PT J AU BLANK, AS AF BLANK, AS TI CLINICAL DETECTION, DIAGNOSIS, AND DIFFERENTIAL-DIAGNOSIS OF POSTTRAUMATIC-STRESS-DISORDER SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; CHILD SEXUAL ABUSE; WORLD-WAR-II; POSTTRAUMATIC-STRESS; VIETNAM VETERANS; MULTIPLE PERSONALITY; DSM-IV; PSYCHOPHYSIOLOGICAL ASSESSMENT; COMBAT VETERANS; PHYSICAL ABUSE C1 US DEPT VET AFFAIRS,READJUSTMENT COUNSELING SERV,WASHINGTON,DC. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC 20007. NR 208 TC 26 Z9 30 U1 3 U2 4 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 JUN PY 1994 VL 17 IS 2 BP 351 EP 383 PG 33 WC Psychiatry SC Psychiatry GA NR151 UT WOS:A1994NR15100010 PM 7937364 ER PT J AU GERWECK, LE DULLEA, R ZAIDI, ST BUDACH, W HARTFORD, A AF GERWECK, LE DULLEA, R ZAIDI, ST BUDACH, W HARTFORD, A TI INFLUENCE OF EXPERIMENTAL FACTORS ON INTRINSIC RADIOSENSITIVITY ASSAYS AT LOW-DOSES OF RADIATION - CELL MULTIPLICITY SO RADIATION RESEARCH LA English DT Article ID HUMAN-TUMORS; SENSITIVITY; RADIORESPONSIVENESS; CARCINOMA; SPECIMENS; INVITRO AB Evaluation of the probability of biological phenomena per cell by colony formation, requires knowledge not only of the number of cells at risk but also of their microdistribution. In the present study, the influence of cellular multiplicity (number of cells per potential colony-forming unit) on the determination of radiation sensitivity is evaluated for a range of multiplicity distributions. Cell surviving fraction was calculated using no multiplicity correction, an average multiplicity correction or the fractional distribution of multiplicities of the control and irradiated population. The results obtained show that: (a) multiplicity corrections are required when the number of cells per potential colony-forming unit is greater than 1.00 either immediately after plating or at the time of irradiation; (b) both the control and irradiated populations must be corrected for multiplicity; (c) multiplicity errors are most pronounced in the low-dose range, e.g. in the survival range with 2 Gy; and (d) the error introduced by using an average vs fractional distribution of multiplicities increases with the multiplicity dispersion. Seemingly small errors due to uncorrected multiplicity effects lead to markedly different predicted isoeffect doses when amplified through multiple (e.g. 30) fractions. RP GERWECK, LE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,EDWIN L STEELE LAB RADIAT BIOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA-22860] NR 15 TC 13 Z9 13 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 1994 VL 138 IS 3 BP 361 EP 366 DI 10.2307/3578684 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA NP025 UT WOS:A1994NP02500008 PM 8184010 ER PT J AU HALLAHAN, DE BLEAKMAN, D VIRUDACHALAM, S LEE, D GRDINA, D KUFE, DW WEICHSELBAUM, RR AF HALLAHAN, DE BLEAKMAN, D VIRUDACHALAM, S LEE, D GRDINA, D KUFE, DW WEICHSELBAUM, RR TI THE ROLE OF INTRACELLULAR CALCIUM IN THE CELLULAR-RESPONSE TO IONIZING-RADIATION SO RADIATION RESEARCH LA English DT Article ID PROTEIN-KINASE-C; CYCLE PROGRESSION; HUMAN-FIBROBLASTS; DNA-REPLICATION; X-IRRADIATION; JUN; EXPRESSION; ACTIVATION; CELLS; MODULATION AB Calcium is required as a cofactor by primer recognition proteins involved in DNA synthesis and by protein kinase C (PKC), which is activated by ionizing radiation. Because these processes may be involved in radiation-mediated regulation of the progression of cells through the phases of the cell cycle, we studied the effects of the intracellular Ca2+ chelator, acetoxymethyl-1,2-bis(2-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (AM-BAPTA), on PKC activation, expression of c-jun and Gadd45 and distribution of cells in the phases of the cell cycle after irradiation. AM-BAPTA prevented ionizing-radiation-induced activation of PKC and expression of c-jun in cells of human tumor cell lines. Conversely, calcium chelation had no effect on X-ray-induced expression of the Gadd45 gene. To determine whether changes in the intracellular Ca2+ concentration ([Ca2+](i)) occurred during irradiation, we measured [Ca2+](i) in single cells using fura-2-based microfluorimetry. There was no increase in [Ca2+](i) during or after irradiation of cells of the human tumor cell lines RIT-3, SQ-20B or HL-60 or normal human fibroblast strain IMR-90. The percentage of human tumor cells crossing the G(1)/S-phase border was reduced by pretreatment with AM-BAPTA. These data indicate that calcium is required for ionizing radiation-induced cell cycle regulation and PKC activation, but that increases in [Ca2+](i) do not occur in cells of the cell lines irradiated in this study. C1 UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL SCI,CHICAGO,IL 60637. PRITZKER SCH MED,CHICAGO,IL 60637. ARGONNE NATL LAB,CTR MECHANIST BIOL & BIOTECHNOL,ARGONNE,IL 60439. DANA FABER CANC INST,CLIN PHARMACOL LAB,BOSTON,MA 02115. FU NCI NIH HHS [NCI CA41068, NCI CA37435, NCI CA58508] NR 46 TC 32 Z9 33 U1 0 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 1994 VL 138 IS 3 BP 392 EP 400 DI 10.2307/3578688 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA NP025 UT WOS:A1994NP02500012 PM 8184014 ER PT J AU HULKA, CA HALL, DA MCCARTHY, K SIMEONE, JF AF HULKA, CA HALL, DA MCCARTHY, K SIMEONE, JF TI ENDOMETRIAL POLYPS, HYPERPLASIA, AND CARCINOMA IN POSTMENOPAUSAL WOMEN - DIFFERENTIATION WITH ENDOVAGINAL SONOGRAPHY SO RADIOLOGY LA English DT Article DE UTERINE NEOPLASMS, US; UTERUS, ENDOMETRIUM ID BREAST-CANCER; PATHOLOGICAL CORRELATION; REPLACEMENT THERAPY; THICKNESS; TAMOXIFEN; ULTRASONOGRAPHY; ABNORMALITIES AB PURPOSE: To characterize endometrial polyps, hyperplasia, and carcinoma with endovaginal ultrasound in postmenopausal women. MATERIALS AND METHODS: Seventy-three postmenopausal women with abnormally thick endometria on endovaginal sonograms were retrospectively identified. The endometrial appearance was characterized as hyperechoic, containing cystic spaces, or heterogeneous. The final study group consisted of 68 women, in whom the pathologic and sonographic findings were correlated. RESULTS: Thirty sonograms showed hyperechoic endometria in women with hyperplasia (n = 8), polyps (n = 4), polyps and hyperplasia (n = 2), or atrophy, proliferative change, mild atypia, or normal endometria (n = 16); 27 sonograms showed cystic spaces in women with polyps (n = 21), carcinoma (n = 1), polyps and hyperplasia (n = 2), or atrophy (n = 3); and 11 sonograms showed heterogeneous endometria in women with endometrial carcinoma (n = 7), atrophy (n = 2), proliferative endometrium (n = 1), or secretory endometrium (n = 1). Cystic spaces were Predictive of polyps (P = 1.19 x 10(-10)). CONCLUSION: Endovaginal sonography may be useful for differentiation of endometrial polyps, hyperplasia, and carcinoma. RP HULKA, CA (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL ACC2,FRUIT ST,BOSTON,MA 02114, USA. NR 17 TC 62 Z9 65 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 JUN PY 1994 VL 191 IS 3 BP 755 EP 758 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NM668 UT WOS:A1994NM66800028 PM 8184058 ER PT J AU KOPANS, DB MCCARTHY, KA HALL, DA WHITMAN, GJ HULKA, CA MCGINTY, GB BRADLEY, FM AF KOPANS, DB MCCARTHY, KA HALL, DA WHITMAN, GJ HULKA, CA MCGINTY, GB BRADLEY, FM TI A SIMPLE DEVICE TO ASSIST IN NEEDLE POSITIONING PROCEDURES SO RADIOLOGY LA English DT Note DE BREAST, BIOPSY; BREAST NEOPLASMS, LOCALIZATION ID BREAST LESION LOCALIZER AB At breast biopsy, use of a simple disk that fits into the hub of the needle can facilitate accurate placement of the needle with conventional lesion localization techniques. This disk forms a surface onto which the shadows of the localization crosshairs project so that the operator can advance the needle and maintain its alignment in the direction of the mammography beam by using the field light. The insert has been used successfully in more than 100 procedures. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP KOPANS, DB (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,LEVEL 2,ROOM 219,32 FRUIT ST,BOSTON,MA 02114, USA. OI McGinty, Geraldine/0000-0001-6111-2514 NR 6 TC 0 Z9 0 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 JUN PY 1994 VL 191 IS 3 BP 868 EP 869 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NM668 UT WOS:A1994NM66800051 PM 8184081 ER EF