FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Calautti, E Cabodi, S Dotto, GP AF Calautti, E Cabodi, S Dotto, GP TI Role of CRIK, a novel epithelial-specific serine-threonine kinase, in keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 605 BP 623 EP 623 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800626 ER PT J AU Gonzalez, S Rajadhyaksha, M Menaker, G Fewkes, JL Anderson, RR AF Gonzalez, S Rajadhyaksha, M Menaker, G Fewkes, JL Anderson, RR TI Does confocal reflectance microscopy help demarcation and screening of non-pigmented skin neoplasms? SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, Cambridge, MA 02138 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Henrietts, Lucid, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 646 BP 630 EP 630 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800669 ER PT J AU Kishimoto, J Ehana, R Burgeson, R AF Kishimoto, J Ehana, R Burgeson, R TI Versican promoter transactivation in dermal papilla as a marker for hair inductive activity: Novel approach to isolate fresh interfollicular dermal papilla cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 678 BP 635 EP 635 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800699 ER PT J AU Baden, L Suga, Y Arin, M Scott, G Goldsmith, L Magro, C Baden, H Roop, D AF Baden, L Suga, Y Arin, M Scott, G Goldsmith, L Magro, C Baden, H Roop, D TI Hot spot mutations in keratin 2E suggest a correlation between genotype and phenotype in patients with ichthyosis bullosa of Siemens SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Univ Rochester, Dept Dermatol, Sch Med, Rochester, NY 14627 USA. Univ Rochester, Dept Pathol, Sch Med, Rochester, NY 14627 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 705 BP 640 EP 640 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800725 ER PT J AU Brancaleon, L Bamberg, M Kollias, N AF Brancaleon, L Bamberg, M Kollias, N TI In vivo infrared analysis of the recovery of sebaceous lipids after delipidation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RI Brancaleon, Lorenzo/B-5625-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 779 BP 652 EP 652 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800796 ER PT J AU Lee, S Kollias, N McAuliffe, D Flotte, T Doukas, A AF Lee, S Kollias, N McAuliffe, D Flotte, T Doukas, A TI Transcutaneous molecular delivery in vivo with a single mechanical pulse SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Med Sch, Dept Dermatol, Boston, MA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 776 BP 652 EP 652 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800797 ER PT J AU Lee, S Gonzalez, S McAuliffe, D Kollias, N Doukas, A AF Lee, S Gonzalez, S McAuliffe, D Kollias, N Doukas, A TI Rapid antigen delivery with photomechanical waves for inducing allergic skin reaction SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 780 BP 652 EP 652 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800799 ER PT J AU Velasco, P Richard, L Hunter, W Toleikis, P Detmar, M AF Velasco, P Richard, L Hunter, W Toleikis, P Detmar, M TI Paclitaxel: Anti-angiogenic effects in vitro and inhibition of experimental skin inflammation in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Angiotech Pharmaceut Inc, Vancouver, BC, Canada. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 795 BP 655 EP 655 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800813 ER PT J AU Nghiem, P Desai, B Schreiber, SL AF Nghiem, P Desai, B Schreiber, SL TI PIK-related kinases in the response to DNA damage by UV SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Ctr Cutaneous Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 805 BP 657 EP 657 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800830 ER PT J AU Kossodo, S Simon, G Kochevar, IE AF Kossodo, S Simon, G Kochevar, IE TI Direct and indirect effects of ultraviolet radiation on collagen synthesis by fibroblasts in collagen gels SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1999 VL 112 IS 4 MA 811 BP 658 EP 658 PG 1 WC Dermatology SC Dermatology GA 182JL UT WOS:000079495800836 ER PT J AU Koike, G Grigor, MR Harris, EL Jacob, HJ Sassard, J AF Koike, G Grigor, MR Harris, EL Jacob, HJ Sassard, J TI Implication for genetic studies of human complex diseases from results obtained in genetic hypertension in rats. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Univ Otago, Dunedin, New Zealand. Fac Pharm Lyon, Lyon, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD APR PY 1999 VL 47 IS 4 SU S BP 196A EP 196A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 182AV UT WOS:000079477100100 ER PT J AU Poniachik, J Baraona, E Zhao, JB Lieber, CS AF Poniachik, J Baraona, E Zhao, JB Lieber, CS TI Dilinoleoylphosphatidylcholine decreases hepatic stellate cell activation SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID FAT-STORING CELLS; CULTURED HUMAN-FIBROBLASTS; COLLAGEN GENE-EXPRESSION; ALCOHOLIC LIVER-DISEASE; LIPID-PEROXIDATION; RAT-LIVER; TRANSITIONAL CELLS; OXIDATIVE STRESS; INTERFERON-GAMMA; ASCORBIC-ACID AB The prevention of cirrhosis in alcohol-fed baboons by the administration of a soybean extract-43% to 50% of which was dilinoleoyl-phosphatidylcholine (DLPC) and 24% of which was 1,palmitoyl 2,linoleoyl-phosphatidylcholine (PLPC)-was associated with a significant reduction in the number of stellate cells transformed to myofibroblast-like cells. To study whether these two major phospholipids affect the similar transformation that occurs by culturing stellate cells on uncoated plastic, we assessed their effects on proliferation (by (methyl-(3)H)-thymidine incorporation into DNA), expression of a-smooth muscle actin and type I procollagen (by densitometry of Western blots), and collagen synthesis (by incorporation of tritiated proline into collagenase-digestible proteins). These manifestations of stellate cell activation were decreased by 10 mu mol/L DLPC but not by in mu mol/L PLPC when compared with controls incubated either with 17 mmol/L ethanol (used as solvent for the phospholipids) or without addition. These agents did not affect cell viability, contamination with other cells, or the capacity of stellate cells to synthesize protein. Thus DLPC specifically decreases the in vitro activation of stellate cells, as judged by the decreases in proliferative activity, a-smooth muscle actin and procollagen I expressions, and collagen synthesis, whereas PLPC did not show such effects. alpha(1)-Procollagen (type I) mRNA was not affected by DLPC, suggesting a posttranslational effect. The reduction in the activation of hepatic stellate cells by DLPC may be responsible for, or at least contribute to, the prevention of fibrosis by the polyenylphosphatidylcholine mixture administered in vivo. C1 Bronx Vet Affairs Med Ctr, Ctr Alcohol Res & Treatment, Sect Liver Dis & Nutr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY 10029 USA. RP Lieber, CS (reprint author), Vet Affairs Med Ctr, Alcohol Res Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIAAA NIH HHS [AA 07275, AA11115] NR 32 TC 34 Z9 36 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD APR PY 1999 VL 133 IS 4 BP 342 EP 348 DI 10.1016/S0022-2143(99)90064-1 PG 7 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 183RB UT WOS:000079566300004 PM 10218764 ER PT J AU Hanstein, B Flototto, T Niederacher, D Bender, HG Brown, M AF Hanstein, B Flototto, T Niederacher, D Bender, HG Brown, M TI Characterization and expression of an (ER)-beta isoform, ER beta 2. SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Meeting Abstract C1 Univ Dusseldorf, Dept Obstet & Gynecol, D-4000 Dusseldorf, Germany. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD APR PY 1999 VL 77 IS 4 BP B11 EP B11 PG 1 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 188HC UT WOS:000079839900034 ER PT J AU Carroll, RS Zhang, J Black, PM AF Carroll, RS Zhang, J Black, PM TI Expression of estrogen receptors alpha and beta in human meningiomas SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE meningioma; estrogen receptor; reverse transcription-polymerase chain reaction ID SEX STEROID-RECEPTORS; PROGESTERONE RECEPTORS; BINDING-ACTIVITY; MESSENGER-RNA; BREAST-CANCER; TISSUE; GROWTH; TUMORS; DNA; IMMUNOREACTIVITY AB The predominance of meningiomas in females, their accelerated growth during the luteal phase of the menstrual cycle and during pregnancy; and the association between meningiomas and breast cancer has led to a number of studies examining the potential role of steroids on the growth of meningiomas. It is generally agreed that the majority of meningiomas possess the progesterone and androgen receptor. There are numerous discrepancies in the literature among the results for estrogen receptor (ER). The aim of this study was to examine the expression of ER-alpha mRNA and the recently described novel ER, ER-beta in meningiomas. Using reverse transcription and polymerase chain reaction (RT-PCR) Southern blot analysis thirty-four meningiomas were examined for the presence of ER-alpha and ER-beta. Forty-four percent of meningiomas showed a strong band for ER-beta mRNA and sixty-eight percent of meningiomas showed a strong band for ER-alpha mRNA. The involvement of ER-beta in meningioma biology should be examined further, given the differences in the ER-alpha and ER-beta gene products. C1 Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. Brigham & Womens Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Carroll, RS (reprint author), Brigham & Womens Hosp, Neurosurg Labs, 221 Longwood Ave,Rm 121, Boston, MA 02115 USA. NR 50 TC 48 Z9 53 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD APR PY 1999 VL 42 IS 2 BP 109 EP 116 DI 10.1023/A:1006158514866 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 204EM UT WOS:000080750700003 PM 10421067 ER PT J AU Chou, YK Bourdette, DN Barnes, D Finn, TP Murray, S Unsicker, L Robey, I Whitham, RH Buenafe, AC Allegretta, M Offner, H Vandenbark, AA AF Chou, YK Bourdette, DN Barnes, D Finn, TP Murray, S Unsicker, L Robey, I Whitham, RH Buenafe, AC Allegretta, M Offner, H Vandenbark, AA TI IL-7 enhances Ag-specific human T cell response by increasing expression of IL-2R alpha and gamma chains SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE IL-7; IL-2R; human T cells; survival factor ID MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS; PROTEOLIPID PROTEIN; CEREBROSPINAL-FLUID; INTERLEUKIN-7 IL-7; BCL-2 EXPRESSION; CDR2 PEPTIDES; GROWTH-FACTOR; KILLER-CELLS; IN-VITRO AB Interleukin-7 has demonstrated potent enhancing effects on the growth and differentiation of several immature cell types, including thymocytes, and on survival of resting and antigen activated T cells. In this study, we evaluated the effects of IL-7 on post-thymic antigen-specific T cells from human blood. IL-7 was found to enhance proliferation responses and IFN-gamma secretion of myelin or recall Ag-specific Th1 cells through the selective up-regulation of the IL-2R alpha and gamma but not beta chains in both an Ag-dependent and Ag-independent manner, but did not affect monocytes, B cells, or NK cells. These functions of IL-7 enhanced the detection of Th1 but not Th2 cell frequency by > 2.5 fold, and promoted selection of kg-specific Th1 cells by the limiting dilution method. Moreover, IL-7 pretreatment conferred increased resistance of CD4 + T cells to CD8 + cell lysis, These studies demonstrate that IL-7 promotes the growth and survival of circulating Ag-specific human Th1 cells through a mechanism that probably involves the gamma c common receptor for IL-2 family members that includes IL-7. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Vet Affairs Med Ctr, Serv Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Connet Corp, Palo Alto, CA 94303 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Chou, YK (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM barnesd@ohsu.edu FU NINDS NIH HHS [NS23221, NS23444] NR 43 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR 1 PY 1999 VL 96 IS 1 BP 101 EP 111 DI 10.1016/S0165-5728(99)00002-8 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 186BT UT WOS:000079707500011 PM 10227429 ER PT J AU Holt, JR Johns, DC Wang, S Chen, ZY Dunn, RJ Marban, E Corey, DP AF Holt, JR Johns, DC Wang, S Chen, ZY Dunn, RJ Marban, E Corey, DP TI Functional expression of exogenous proteins in mammalian sensory hair cells infected with adenoviral vectors SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INWARDLY RECTIFYING CURRENTS; GREEN FLUORESCENT PROTEIN; MOUSE UTRICLE; IN-VIVO; ADENOASSOCIATED VIRUS; GUINEA-PIG; TRANSDUCTION; DYSTROPHIN; COCHLEA; CHICK AB To understand the function of specific proteins in sensory hair cells, it is necessary to add or inactivate those proteins in a system where their physiological effects can be studied. Unfortunately, the usefulness of heterologous expression systems for the study of many hair cell proteins is limited by the inherent difficulty of reconstituting the hair cell's exquisite cytoarchitecture. Expression of exogenous proteins within hair cells themselves may provide an alternative approach. Because recombinant viruses were efficient vectors for gene delivery in other systems, we screened three viral vectors for their ability to express exogenous genes in hair cells of organotypic cultures from mouse auditory and vestibular organs. We observed no expression of the genes for beta-galactosidase or green fluorescent protein (GFP) with either herpes simplex virus or adeno-associated virus. On the other hand, we found robust expression of GFP in hair cells exposed to a recombinant, replication-deficient adenovirus that carried the gene for GFP driven by a cytomegalovirus promoter. Titers of 4 x 10(7) pfu/ml were sufficient for expression in 50% of the similar to 1,000 hair cells in the utricular epithelium; < 1% of the nonhair cells in the epithelium were GFP positive. Expression of GFP was evident as early as 12 h postinfection, was maximal at 4 days, and continued for at least 10 days. Over the first 36 h there was no evidence of toxicity. We recorded normal voltage-dependent and transduction currents from infected cells identified by GFP fluorescence. At longer times hair bundle integrity was compromised despite a cell body that appeared healthy. To assess the ability of adenovirus-mediated gene transfer to alter hair cell function we introduced the gene for the ion channel Kir2.1. We used an adenovirus vector encoding Kir2.1 fused to GFP under the control of an ecdysone promoter. Unlike the diffuse distribution within the cell body we observed with Gm, the ion channel-GFP fusion showed a pattern of fluorescence that was restricted to the cell membrane and a few extranuclear punctate regions. Patch-clamp recordings confirmed the expression of an inward rectifier with a conductance of 43 nS, over an order of magnitude larger than the endogenous inward rectifier. The zero-current potential in infected cells was shifted by -17 mV. These results demonstrate an efficient method for gene transfer into both vestibular and auditory hair cells in culture, which can be used to study the effects of gene products on hair cell function. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Cambridge, MA 02138 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Sect Mol & Cellular Cardiol, Baltimore, MD 21205 USA. Montreal Gen Hosp, Neurosci Res Ctr, Montreal, PQ H3G 1A4, Canada. RP Corey, DP (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wellman 414, Boston, MA 02114 USA. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [DC-00304, DC-02281, DC-02335] NR 32 TC 61 Z9 64 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 1999 VL 81 IS 4 BP 1881 EP 1888 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 186VW UT WOS:000079752000044 PM 10200223 ER PT J AU Weissig, V Rowe, TC AF Weissig, V Rowe, TC TI Analysis of Plasmodium falciparum mitochondrial six-kilobase DNA by pulse-field electrophoresis SO JOURNAL OF PARASITOLOGY LA English DT Article ID PARASITES; MALARIA; REPLICATION; CULTURE; NUCLEAR AB The 6-kb mtDNA of Plasmodium falciparum is thought to replicate by a recombination-dependent mechanism generating large complex branched structures. For technical reasons, including shearing caused by DNA extraction methods, a meaningful quantitative comparison of large complex mtDNA forms has not been feasible. With the use of pulse-held gel electrophoresis, which minimizes any loss or shearing of DNA, we were able to identify an unusually slow migrating population of mtDNA that was resolved from the 6-23-kb population of linear concatemers. Levels of this slow-migrating population of mtDNA were highest during early schizont stage, suggesting that these forms represent replication intermediates. This approach provides a convenient means to monitor the presence of large mtDNA structures in P. falciparum. C1 Univ Florida, Dept Pharmacol & Therapeut, Coll Med, Gainesville, FL 32610 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. RP Rowe, TC (reprint author), Univ Florida, Dept Pharmacol & Therapeut, Coll Med, Gainesville, FL 32610 USA. FU NIGMS NIH HHS [GM 47535] NR 13 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD APR PY 1999 VL 85 IS 2 BP 386 EP 389 DI 10.2307/3285656 PG 4 WC Parasitology SC Parasitology GA 184XB UT WOS:000079638100040 PM 10219329 ER PT J AU Sherwood, AM AF Sherwood, AM TI Aging in America SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material C1 VA Med Ctr, Ctr Excellence Rehabil Res, Houston, TX 77211 USA. VA Med Ctr, Dev Ctr Healthy Aging Disabil, Houston, TX USA. RP Sherwood, AM (reprint author), VA Med Ctr, Ctr Excellence Rehabil Res, Houston, TX 77211 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD APR PY 1999 VL 36 IS 2 BP VII EP VIII PG 2 WC Rehabilitation SC Rehabilitation GA 288VH UT WOS:000085584800001 PM 10661522 ER PT J AU Cooper, RA Quatrano, LA Axelson, PW Harlan, W Stineman, M Franklin, B Krause, S Bach, J Chambers, S Chao, EYS Alexander, M Painter, P AF Cooper, RA Quatrano, LA Axelson, PW Harlan, W Stineman, M Franklin, B Krause, S Bach, J Chambers, S Chao, EYS Alexander, M Painter, P TI Research on physical activity and health among people with disabilities: A consensus statement SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE disability; exercise; health; paralympics; research priorities ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; MAXIMAL OXYGEN-CONSUMPTION; ARM-CRANK ERGOMETRY; CARDIAC REHABILITATION; MENTAL-RETARDATION; EXERCISE; WHEELCHAIR; PREVENTION; RESPONSES AB Research is required to advance the understanding of issues related to the effect of physical activity on health and disease prevention among people with disabilities. This report is the result of a consensus process using selected experts in health and exercise. The purpose of the consensus conference was to identify research priorities for physical activity and health among people with disabilities. Priorities were established by 30 participants, who were selected by the principal investigators to achieve balance in the areas of engineering, epidemiology, medicine, nutrition, exercise physiology, and psychology. Experts summarized relevant data from their research and from comprehensive review of the scientific literature on the topic areas chosen for the conference. Public commentary was provided by participants in the 1996 Paralympic Congress. Panel members discussed openly all material presented to them in executive session. Commentary from open discussion periods were recorded and transcribed, selected panelists prepared first drafts of the consensus statements for each research priority question. All of these drafts were distributed to the panelists and. pertinent experts. The documents were edited by the drafting committee to obtain consensus. This research priority setting process revealed that greater emphasis must be placed on determining the risks and benefits of exercise among people with disabilities. Exercise must be studied from the perspective of disease prevention while mitigating risk for injury. Five areas were identified as focal points for future work: epidemiological studies; effects of nutrition on health and ability to exercise; cardiovascular and pulmonary health; children with disabilities; and accessibility and safety of exercise programs. As people with disabilities live longer, the need for addressing longterm health issues and risk for secondary disability must receive greater attention. As a consequence of the consensus process, specific recommendations for future research regarding the impact of exercise on the health and quality of life of persons with disabilities were defined. C1 VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151R1, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15206 USA. RP Cooper, RA (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 71 TC 81 Z9 83 U1 2 U2 13 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD APR PY 1999 VL 36 IS 2 BP 142 EP 154 PG 13 WC Rehabilitation SC Rehabilitation GA 288VH UT WOS:000085584800010 PM 10661530 ER PT J AU Licht, EA Sankar, R AF Licht, EA Sankar, R TI Status epilepticus during pregnancy - A case report SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE status epilepticus; pregnancy complications; epilepsy, myoclonic; valproic acid ID EPILEPSY AB BACKGROUND: Status epilepticus is a rare but potentially life threatening complication that women with epilepsy may experience during pregnancy. Poor compliance may contribute to the occurrence of status epilepticus, resulting in the need for substantial increases in anticonvulsant dosing to suppress seizures. CASE: A 39-year-old woman, gravida 2, para 0, abortion 1, with a history of epilepsy since childhood, delivered twins following an episode of myoclonic status epilepticus. The infants tolerated tie maternal seizures and the aggressive anticonvulsant therapy without residual problems. CONCLUSION: Status epilepticus seems more likely to occur in women with epilepsy during the third trimester. Fourteen of 19, or 74%, of cases reviewed, including the case we report on here, experienced status epilepticus in the third trimester or during labor. C1 VA Greater Los Angeles Healthcare Syst Sepulveda, Ctr Study Healthcare Provider Behav, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. RP Licht, EA (reprint author), VA Greater Los Angeles Healthcare Syst Sepulveda, Ctr Study Healthcare Provider Behav, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 8 TC 5 Z9 6 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD APR PY 1999 VL 44 IS 4 BP 370 EP 372 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 189TA UT WOS:000079921200012 PM 10319309 ER PT J AU Souba, WW AF Souba, WW TI Mentoring young academic surgeons, our most precious asset SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 18-22, 1998 CL SEATTLE, WASHINGTON SP Assoc Acad Surg C1 Harvard Univ, Div Surg Oncol, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Souba, WW (reprint author), Harvard Univ, Div Surg Oncol, Massachusetts Gen Hosp, Dept Surg, Cox 626,100 Blossom St, Boston, MA 02114 USA. NR 10 TC 41 Z9 42 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD APR PY 1999 VL 82 IS 2 BP 113 EP 120 DI 10.1006/jsre.1999.5596 PG 8 WC Surgery SC Surgery GA 184KN UT WOS:000079611500001 PM 10090818 ER PT J AU Boppart, SA Herrmann, J Pitris, C Stamper, DL Brezinski, ME Fujimoto, JG AF Boppart, SA Herrmann, J Pitris, C Stamper, DL Brezinski, ME Fujimoto, JG TI High-resolution optical coherence tomography-guided laser ablation of surgical tissue SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE laser surgery; imaging; ablation; neoplasia; tumor ID ND-YAG LASER; BIOLOGICAL TISSUE; IN-VIVO; BIOPSY; MICROSURGERY; THERAPY AB Background. Optical coherence tomography (OCT) is a compact high-speed imaging technology which uses infrared light to acquire cross-sectional images of tissue on the micrometer scale. Because OCT images are based on the optical backscattering properties of tissue, changes in tissue optical properties due to surgical laser ablation should be detectable using this technique. In this work, we examine the feasibility of using real-time OCT imaging to guide the placement and observe the dynamics of surgical laser ablation in a variety of tissue types. Materials and methods. More than 65 sites on five ex vivo rat organ tissue types were imaged at eight frames per second before, during, and after laser ablation, Ablation was performed with a coincident continuous wave argon laser operating at 514-nm wavelength and varying exposure powers and durations, Following imaging, tissue registration was achieved using microinjections of dye followed by routine histologic processing to confirm the morphology of the ablation site. Results. High-speed OCT imaging at eight frames per second permitted rapid tissue orientation and guided ablation in numerous organ specimens. Acquisition rates were fast enough to capture dynamic changes in optical backscatter which corresponded to thermal tissue damage during laser ablation, Conclusions. The ability of high-resolution highspeed OCT to guide laser ablation and image the dynamic changes suggests a role in image-guided surgical procedures, such as the ablation of neoplasms. Future in vivo studies are necessary to demonstrate performance intraoperatively. (C) 1999 Academic Press. C1 MIT, Dept Comp Sci & Elect Engn, Elect Res Lab, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Univ London Kings Coll, Dept Biol, Wilkes Barre, PA 18711 USA. Massachusetts Gen Hosp, Harvard Med Sch, Cardiac Unit, Boston, MA 02114 USA. RP Boppart, SA (reprint author), MIT, Dept Comp Sci & Elect Engn, Elect Res Lab, Div Hlth Sci & Technol, 77 Massachusetts Ave,Room 36-345, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NCI NIH HHS [NIH-9-RO1-CA75289-01]; NEI NIH HHS [NIH-9-RO1-EY11289-13]; NIAMS NIH HHS [NIH-9-RO1-AR44812-01] NR 30 TC 76 Z9 80 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD APR PY 1999 VL 82 IS 2 BP 275 EP 284 DI 10.1006/jsre.1998.5555 PG 10 WC Surgery SC Surgery GA 184KN UT WOS:000079611500023 PM 10090840 ER PT J AU Biederman, J Faraone, SV Chu, MP Wozniak, J AF Biederman, J Faraone, SV Chu, MP Wozniak, J TI Further evidence of a bidirectional overlap between juvenile mania and conduct disorder in children SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE mania; bipolar disorder; conduct disorder ID DEFICIT HYPERACTIVITY DISORDER; BIPOLAR DISORDER; ONSET MANIA; COMORBIDITY; RELIABILITY; CHILDHOOD; ADHD; ADOLESCENCE; INTERVIEW; BEHAVIOR AB Objective: To investigate systematically the overlap between mania and conduct disorder (CD) in a sample of consecutively referred youths. It was hypothesized that neither CD nor manic symptoms were secondary to the other disorder and that children with the 2 disorders would have correlates of both. Method: Subjects were consecutively referred children and adolescents meeting DSM-III-R diagnostic criteria on structured diagnostic interview for CD (n = 116), mania (n = 110), and CD+mania (n = 76). Results: Of 186 children and adolescents with mania and of 192 with CD, 76 satisfied criteria for both CD and mania, representing 40% of youths with CD and 41% of youths with mania, respectively. Examination of the clinical features, patterns of psychiatric comorbidity, and functioning in multiple domains showed that children with CD and mania had similar features of each disorder irrespective of the comorbidity with the other disorder. Conclusions: The data suggest that when mania and CD co-occur in children, both are correctly diagnosed. In these comorbid cases, CD symptoms should not be viewed as secondary to mania and manic symptoms should not be viewed as secondary to CD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Child Psychiat Serv,Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Biederman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Child Psychiat Serv,Pediat Psychopharmacol Unit, ACC 725,Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 34 TC 94 Z9 95 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1999 VL 38 IS 4 BP 468 EP 476 DI 10.1097/00004583-199904000-00021 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 179ZJ UT WOS:000079360000021 PM 10199120 ER PT J AU Knight, EL Fish, LC Kiely, DK Marcantonio, ER Davis, KM Minaker, KL AF Knight, EL Fish, LC Kiely, DK Marcantonio, ER Davis, KM Minaker, KL TI Atrial natriuretic peptide and the development of congestive heart failure in the oldest old: A seven-year prospective study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE atrial natriuretic peptide; congestive heart failure; oldest old ID ACUTE MYOCARDIAL-INFARCTION; RISK-FACTORS; PLASMA; POLYPEPTIDE; POPULATION; SECRETION; VENTRICLE; MEN AB BACKGROUND: Atrial natriuretic peptide (ANP) levels are elevated in symptomatic heart failure and correlate with invasively measured left heart pressures. OBJECTIVE: To examine the association between plasma ANT level and the subsequent development of congestive heart failure (CHF) in older subjects with no history of CHF. DESIGN: A 7-year, prospective, blinded, cohort study. SETTING: A life care facility in Boston, Massachusetts. PARTICIPANTS: Two hundred fifty-six frail older subjects (mean age 88 +/- 7) with no history of CHF at study entry. MAIN OUTCOME MEASURE: Clinical episodes of CHF with confirmatory chest roentgenogram findings. Cox proportional hazard analyses were performed to examine the relationship between ANP levels and the development of CHF while controlling for 19 clinical, physical, and laboratory parameters. A Kaplan-Meier estimator (log-rank test) was used to determine if the development of CHF differed by tertile of ANP. RESULTS: During the follow-up period, 32% of the cohort developed CHF. The mean ANP level in the CHF group was 95 pmol/L +/- 11 pmol/L versus 60 pmol/L +/- 5 pmol/L in the no CHF group (two tailed t test P = .005). On multivariate analysis, a high ANP level was found to be associated significantly (P = .01) with the development of CHF. CONCLUSIONS: There is a statistically significant association between ANP level and the subsequent development of CHF in frail older individuals with no history of CHF. C1 Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. N Mississippi Med Ctr, Tupelo, MS 38801 USA. RP Knight, EL (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 221 Longwood Ave, Boston, MA 02115 USA. FU NCRR NIH HHS [RR-01032]; NIA NIH HHS [AG-00599, AG-04390] NR 33 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 1999 VL 47 IS 4 BP 407 EP 411 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 184BZ UT WOS:000079590600004 PM 10203114 ER PT J AU Fitzgibbon, WR Greene, EL Grewal, JS Hutchison, FN Self, SE Latten, SY Ullian, ME AF Fitzgibbon, WR Greene, EL Grewal, JS Hutchison, FN Self, SE Latten, SY Ullian, ME TI Resistance to remnant nephropathy in the Wistar-Furth rat SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID KIDNEY MODEL; GLOMERULAR INJURY; SALT HYPERTENSION; RENAL-DISEASE; ALDOSTERONE; EXPRESSION AB The Wistar-Furth rat, an inbred strain resistant to actions of mineralocorticoids, was used to study the concept that mineralocorticoids contribute to progressive renal injury. It was postulated that if chronic nephropathy depends on aldosterone and if Wistar-Furth rats are resistant to aldosterone, remnant nephropathy would be attenuated in Wistar-Furth rats. Wistar-Furth rats and control Wistar rats were subjected to 5/6 nephrectomy or a sham procedure and then followed for 4 wk. Renal ablation resulted in hypertension at 4 wk in both strains (164 +/- 5 [Wistar-Furth] versus 184 +/- 7 [Wistar] mmHg mean arterial pressure), with sham animals remaining normotensive (134 +/- 6 mmHg). Renal damage in response to 5/6 nephrectomy was greatly decreased in Wistar-Furth rats compared with Wistar rats. Albuminuria was markedly less in Wistar-Furth rats (12.7 +/- 4.2 [Wistar-Furth] versus 97.4 +/- 22.6 [Wistar] mg/d per 100 g body wt, P < 0.01). Glomerular damage, consisting of mesangial proliferation, mesangial lysis, and seg mental necrosis, was observed in 42% of glomeruli from Wistar rats but in 0% of glomeruli from Wistar-Furth rats (P < 0.01). To address the possibility that higher BP in partially nephrectomized Wistar rats mediated the greater renal damage, the study was repeated, with Wistar rats (not Wistar-Furth rats) being treated with a hydralazine-reserpine-hydrochlorothiazide regimen. Although this antihypertensive regimen equalized BP (conscious systolic) (144 +/- 8 mmHg [Wistar] versus 157 +/- 7 mmHg [Wistar-Furth] at 4 wk), albuminuria remained more than 10-fold greater in Wistar rats. In summary, renal damage upon 5/6 nephrectomy was markedly reduced in Wistar-Furth rats, a finding not attributable to reduced systemic BP. Since Wistar-Furth rats have been shown previously to be resistant to the actions of mineralocorticoids, the data from the present study support the hypothesis that aldosterone mediates, at least in part, the renal injury attendant to renal mass reduction. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol Lab Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Ullian, ME (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, 171 Ashley Ave, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL03710] NR 21 TC 24 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 1999 VL 10 IS 4 BP 814 EP 821 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 180BW UT WOS:000079365900016 PM 10203366 ER PT J AU Curhan, GC Willett, WC Speizer, FE Stampfer, MJ AF Curhan, GC Willett, WC Speizer, FE Stampfer, MJ TI Intake of vitamins B6 and C and the risk of kidney stones in women SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID URINARY OXALATE LEVELS; HEALTHY-SUBJECTS; ASCORBIC-ACID; CALCIUM; PYRIDOXINE; FORMERS; NEPHROLITHIASIS; DIET AB Urinary oxalate is an important determinant of calcium oxalate kidney stone formation. High doses of vitamin B6 may decrease oxalate production, whereas vitamin C can be metabolized to oxalate. This study was conducted to examine the association between the intakes of vitamins B6 and C and risk of kidney stone formation in women. The relation between the intake of vitamins B6 and C and the risk of symptomatic kidney stones were prospectively studied in a cohort of 85,557 women with no history of kidney stones. Semiquantitative food-frequency questionnaires were used to assess vitamin consumption from both foods and supplements. A total of 1078 incident cases of kidney stones was documented during the 14-yr follow-up period. A high intake of vitamin B6 was inversely associated with risk of stone formation. After adjusting for other dietary factors, the relative risk of incident stone formation for women in the highest category of B6 intake (greater than or equal to 40 mg/d) compared with the lowest category (<3 mg/d) was 0.66 (95% confidence interval, 0.44 to 0.98). In contrast, vitamin C intake was not associated with risk. The multivariate relative risk for women in the highest category of vitamin C intake (greater than or equal to 1500 mg/d) compared with the lowest category (<250 mg/d) was 1.06 (95% confidence interval, 0.69 to 1.64). Large doses of vitamin B6 may reduce the risk of kidney stone formation in women. Routine restriction of vitamin C to prevent stone formation appears unwarranted. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Curhan, GC (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA40356]; NIDDK NIH HHS [DK45362] NR 26 TC 80 Z9 83 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 1999 VL 10 IS 4 BP 840 EP 845 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 180BW UT WOS:000079365900019 PM 10203369 ER PT J AU Felsenfeld, AJ Rodriguez, M AF Felsenfeld, AJ Rodriguez, M TI Phosphorus, regulation of plasma calcium, and secondary hyperparathyroidism: A hypothesis to integrate a historical and modern perspective SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID PARATHYROID-HORMONE LEVELS; RENAL-FAILURE; CALCEMIC RESPONSE; IN-VITRO; REPLACEMENT THERAPY; PTH SECRETION; HEALTHY-MEN; CALCITRIOL; WOMEN; AGE C1 W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, Dept Med, Los Angeles, CA 90073 USA. Hosp Reina Sofia, Dept Nephrol, Cordoba, Spain. Hosp Reina Sofia, Unit Investigat, Cordoba, Spain. RP Felsenfeld, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Rodriguez, teresa/H-5452-2011 NR 56 TC 37 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 1999 VL 10 IS 4 BP 878 EP 890 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 180BW UT WOS:000079365900024 PM 10203374 ER PT J AU Macchiarini, P Wain, J Almy, S Dartevelle, P AF Macchiarini, P Wain, J Almy, S Dartevelle, P TI Experimental and clinical evaluation of a new synthetic, absorbable sealant to reduce air leaks in thoracic operations SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID COMPLICATIONS; RESECTION; LUNG AB Background: Air leaks after pulmonary resections may contribute to increased patient morbidity, delayed removal of chest drainage tubes, and prolonged hospitalization. Objective: The purpose of this study was to investigate the effects of a new synthetic, absorbable sealant on the healing of healthy bronchial and lung tissues (experimental study) and its safety and efficacy to stop air leaks after lung resection (clinical study), Methods: Fifteen large white pigs underwent a left upper lobectomy, All parenchymal surgical sites were sealed; the bronchial stump was either stapled, sealed, or both (n = 5 each), In the clinical study, 26 consecutive patients were prospectively randomized, intraoperatively, to standard closure of parenchymal surgical sites with (n = 15) or without (n = 11) the sealant, Results: In the experimental study, no postoperative air leaks occurred, with intact bronchial closures and normal tissues at death, In the clinical study, 100% of intraoperative leaks were sealed versus 18% of control patients (P = .001), Although 77% (n = 10) of treated patients remained leak-free from the end of the operation to chest tube removal versus 9% (n = 1) of control patients (P = .001), there was no statistical difference in the duration of postoperative chest tube time, hospital stay, or cost. There were no acute or late undesirable side-effects related to the sealant application, Conclusions: The surgical adhesive investigated here demonstrated a compelling safety profile and significant clinical efficacy to stop air leaks after lung resections. C1 Univ Paris Sud, Hop Marie Lannelongue, Dept Thorac & Vasc Surg, Le Plessis Robinson, France. Univ Paris Sud, Hop Marie Lannelongue, Dept Heart Lung Transplantat, Le Plessis Robinson, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Thorac Surg, Boston, MA USA. Stat Unlimited Inc, Westford, MA USA. RP Macchiarini, P (reprint author), Hannover Med Sch, Heidehaus Hosp, Dept Thorac & Vasc Surg, 70 Leineufer, D-30419 Hannover, Germany. RI Macchiarini, Paolo/E-6878-2013 NR 12 TC 80 Z9 82 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 1999 VL 117 IS 4 BP 751 EP 758 DI 10.1016/S0022-5223(99)70296-5 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 182VZ UT WOS:000079520000022 PM 10096971 ER PT J AU Fadel, E Riou, JY Mazmanian, M Brenot, P Dulmet, E Detruit, H Serraf, A Bacha, EA Herve, P Dartevelle, P AF Fadel, E Riou, JY Mazmanian, M Brenot, P Dulmet, E Detruit, H Serraf, A Bacha, EA Herve, P Dartevelle, P TI Pulmonary thromboendarterectomy for chronic thromboembolic obstruction of the pulmonary artery in piglets SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID ISCHEMIA-REPERFUSION INJURY; ISOLATED RAT LUNG; VASCULAR-PERMEABILITY; SURGICAL-MANAGEMENT; OCCLUSION; HYPERTENSION; EDEMA AB Objective: The 2 main causes of death after thromboendarterectomy for chronic pulmonary thromboembolism are incomplete repermeabilization responsible for persistent pulmonary hypertension and acute high-permeability pulmonary edema. We wish to establish an experimental model of chronic pulmonary thromboembolism to replicate the conditions encountered during and after pulmonary thromboendarterectomy. Methods: Multiple-curled coils and tissue adhesive were embolized in 6 piglets to induce complete obstruction of the left pulmonary artery, documented by angiography, After 5 weeks, the main pulmonary artery was repermeabilized by thromboendarterectomy during circulatory arrest, The left lung was reperfused ex vivo with autologous blood at constant flow, and patency of the pulmonary artery was evaluated on a barium angiogram, The endarterectomy-reperfusion procedure was also done in 6 nonembolized piglets that served as the controls. The severity of lung injury induced by 60 minutes of reperfusion was assessed on the basis of measurements of the lung filtration coefficient and of lung myeloperoxidase activity. Results: Marked hypertrophy of the bronchial circulation was seen in the chronic pulmonary thromboembolism group, Thromboendarterectomy removed the organized obstructing thrombus that was incorporated into the arterial wall and restored patency of the pulmonary artery. Acute lung inflammation and high-permeability edema occurred after reperfusion, as indicated by a 1.5-fold increases in both lung filtration coefficient and lung myeloperoxidase values in the chronic pulmonary thromboembolism group; these 2 variables being correlated. Conclusions: Our model replicated the perioperative conditions of pulmonary thromboendarterectomy, suggesting that it may prove useful for improving the repermeabilization technique and for investigating the mechanisms and prevention of reperfusion injury. C1 Univ Paris Sud, Ctr Chirurg Marie Lannelongue, Chirurg Expt Lab, F-92250 Le Plessis Robinson, France. Univ Paris Sud, Ctr Chirurg Marie Lannelongue, Dept Radiol, F-92250 Le Plessis Robinson, France. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Fadel, E (reprint author), Univ Paris Sud, Ctr Chirurg Marie Lannelongue, Chirurg Expt Lab, 133 Ave Resistance, F-92250 Le Plessis Robinson, France. NR 21 TC 14 Z9 20 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 1999 VL 117 IS 4 BP 787 EP 793 DI 10.1016/S0022-5223(99)70300-4 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 182VZ UT WOS:000079520000028 PM 10096975 ER PT J AU Oertel, LB AF Oertel, LB TI Anticoagulation services: Quality improvement direction - Pursuing a certification process SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE anticoagulation; certification; warfarin; quality improvement AB There is growing interest in a certification proc ess for anticoagulant therapy providers. The primary, and certainly most important, goal is to improve patient care. Defining measurable competencies to which the anticoagulation provider is made accountable is but one mechanism to help improve quality in patient care. Great improvements have been achieved in the field of anticoagulation. For example, determining optimum intensity levels, for the traditional as well as the newer indications for treatment, have yielded greater efficacy and safety Additionally, the acceptance of the INR reporting system has greatly reduced hemorrhagic and thromboembolic complications. However, the process of care, that is, how patients are managed and by whom, remains a variable that is difficult to quantify and measure. Anticoagulation providers are comprised of professionals from three major disciplines, namely, medicine, nursing, and pharmacy. This multidisciplinary approach enriches the quality of care for patients. However, this very fact presents a dilemma when seeking an appropriate certifying body, Nevertheless, keeping quality patient care as the primary focus, a multidisciplinary group has developed a body of knowledge that is unique to anticoagulant and antithrombotic therapies. The foundation of this project stems from the Fourth American College of Chest Physicians Consensus Conference on Antithrombotic Therapy and the recently published paper by Ansell et al. on consensus guidelines for coordinated outpatient oral anticoagulation therapy management. This work-in-progress includes a mission statement and outlines five major knowledge domains along with measurable competencies for each section, This effort will help standardized the process of care across the country. C1 Massachusetts Gen Hosp ACC 620, Boston, MA 02114 USA. RP Oertel, LB (reprint author), Massachusetts Gen Hosp ACC 620, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD APR PY 1999 VL 7 IS 2 BP 153 EP 156 DI 10.1023/A:1008837621067 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 202ZE UT WOS:000080681600011 PM 10364767 ER PT J AU Taft, CT King, LA King, DW Leskin, GA Riggs, DS AF Taft, CT King, LA King, DW Leskin, GA Riggs, DS TI Partners' ratings of combat veterans' PTSD symptomatology SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE Vietnam veterans; couples; Mississippi Scale; score concordance; PTSD ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM VETERANS; VALIDITY AB The current study examined the concordance of combat veterans' scores on the Mississippi Scale for Combat-Related PTSD, with scores on a parallel version of that instrument completed by partners to assess veterans' symptoms. Further the study examined the impact of quality of the marital relationship on score concordance, Bivariate and multiple regression were used with a sample of 466 veteran-partner dyads obtained from the National Vietnam Veterans Readjustment Study. There was moderate agreement in symptom reporting between veterans and their partners and little evidence to suggest that the quality of the relationship impacted upon the association between partner and veteran scores. C1 Boston Univ, Sch Med, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP King, LA (reprint author), Boston Univ, Sch Med, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02215 USA. NR 14 TC 15 Z9 15 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 1999 VL 12 IS 2 BP 327 EP 334 DI 10.1023/A:1024780610575 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 205YC UT WOS:000080847600008 PM 10378169 ER PT J AU Planz, B Kirley, SD Wang, QF Tabatabaei, S Aretz, HT Mcdougal, WC AF Planz, B Kirley, SD Wang, QF Tabatabaei, S Aretz, HT Mcdougal, WC TI Characterization of a stromal cell model of the human benign and malignant prostate from explant culture SO JOURNAL OF UROLOGY LA English DT Article DE prostate; stromal cells; epithelial cells ID ANDROGEN-RECEPTOR; GROWTH-FACTOR; EPITHELIAL-CELLS; CANCER CELLS; IN-VITRO; DIFFERENTIATION; RESPONSIVENESS; FIBROBLAST; INDUCTION; ESTROGEN AB Purpose: There is a lack of suitable in vitro models for the human prostate. To study stromal-epithelial interactions, we established stromal cells in cultures from benign and malignant prostate tissue that resemble more closely the in vivo conditions of the human prostate. Materials and Methods: Stromal cells were obtained from explant primary culture, established in DU145 cell conditioned medium and maintained in RPMI-fetal bovine serum (FBS) supplemented with insulin, transferrin and selenium (ITS), Proliferation studies to compare different media were performed using a (3)[H]thymidine assay. Stromal cells were characterized by immunocytochemistry using epithelial and mesenchymal markers. Morphology was evaluated by electron microscopy, light and phase-contrast microscopy. Androgen receptor (AR) mRNA expression was measured by polymerase-chain-reaction (PCR). The response to different concentrations of dihydrotestosterone (DHT) and the antihormones flutamide and hydroxyflutamide was tested by 3[H] thymidine assay. Results: Microscopic evaluation revealed typical stromal morphology with elongated cell shapes, cilia, collagen and microfilaments. Immunocytochemical characterization revealed typical fibroblastic and smooth muscle differentiation. ITS supplemented in RPMI-FBS showed the best growth stimulation compared with other serum-free media (p < 0.05) and became our basal medium, The presence of DU145 cell conditioned medium in this basal medium showed a significant increase in cell proliferation in stromal cells. Stromal cells maintained AR mRNA expression and significant DHT dose dependent growth stimulation in up to 10 passages. Both the antiandrogens flutamide and hydroxyflutamide counteracted the DHT effect (p < 0.05). Conclusions: This stromal cell model maintains many cellular and functional properties of the human prostate, which may enable us to study growth factor modulation, drug and hormone metabolism in stromal-epithelial interaction with emphasis on the pathogenesis of BPH and prostate cancer. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Reprod Endocrinol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Planz, B (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. FU NICHD NIH HHS [HD29164] NR 41 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 1999 VL 161 IS 4 BP 1329 EP 1336 DI 10.1016/S0022-5347(01)61679-3 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 174BJ UT WOS:000079014000089 PM 10081903 ER PT J AU Wang, QF Tabatabaei, S Planz, B Lin, CW Sluss, PM AF Wang, QF Tabatabaei, S Planz, B Lin, CW Sluss, PM TI Identification of an activin-follistatin growth modulatory system in the human prostate: Secretion and biological activity in primary cultures of prostatic epithelial cells SO JOURNAL OF UROLOGY LA English DT Article DE prostate; activin; follistatin ID PORCINE FOLLISTATIN; II RECEPTORS; RAT PROSTATE; INHIBIN; CANCER; LNCAP; LINE; EXPRESSION; BINDING; PROLIFERATION AB Purpose: To determine if the activin/follistatin system is present in human prostate tissue and primary cultures of prostatic epithelium and if these growth factors play a role in the control of epithelial cell growth, Materials and Methods: Cells derived directly from human prostates were studied to determine: a) if they secrete activin and follistatin, and b) if they are growth inhibited by activin. Primary cell cultures were established from tissues removed from 13 unselected prostate carcinoma patients in order to examine the secretion of activin and follistatin and test the effects of these proteins on cell proliferation. Results: Both primary explant cells and epithelial cells isolated and sub-cultured from explant cultures secreted activin A and follistatin. Treatment of cultured cells with recombinant human activin A resulted in a dose-dependent inhibition of thymidine incorporation, with an IC50 of 0.22 nM, Recombinant follistatin neutralized the inhibitory effects of activin A on cell proliferation whilst adding follistatin alone enhanced thymidine incorporation, suggesting a similar neutralizing effect on the endogenous activin produced by these cells. Conclusion: These results demonstrate that cells derived from human prostate tissue secrete activin and follistatin and, as observed in human prostate cancer cell lines, activin inhibited the growth of prostatic epithelial cells. Also consistent with our earlier studies of prostate cancer cell lines, the biological activity of activin was neutralized by follistatin. These observations support the hypothesis that the activin/follistatin system plays an important role in the local regulation of human prostate cell growth. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Assay Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Sluss, PM (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Assay Lab, Edwards 003, Boston, MA 02114 USA. FU NICHD NIH HHS [HD29164] NR 40 TC 22 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 1999 VL 161 IS 4 BP 1378 EP 1384 DI 10.1016/S0022-5347(01)61687-2 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 174BJ UT WOS:000079014000097 PM 10081911 ER PT J AU Fadel, E Chapelier, A Bacha, E Leroy-Ladurie, F Cerrina, J Macchiarini, P Dartevelle, P AF Fadel, E Chapelier, A Bacha, E Leroy-Ladurie, F Cerrina, J Macchiarini, P Dartevelle, P TI Subclavian artery resection and reconstruction for thoracic inlet cancers SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID SUPERIOR PULMONARY SULCUS; RADICAL RESECTION; LUNG-TUMORS; BYPASS; EXPERIENCE; REVASCULARIZATION; REPLACEMENT; IRRADIATION; NECK AB Purpose: We previously described an original transcervical approach to resect primary or secondary malignant diseases that invade the thoracic inlet (TI). The purpose of this study was to evaluate the technical aspects and long-term results of the resection and revascularization of the subclavian artery (SA). Methods: Between 1986 and 1998, 34 patients (mean age, 49 years) underwent en bloc resection of TI cancer that had invaded the SA. The surgical approach was an L-shaped transclavicular cervicotomy in 33 patients. In 14 of these patients, this approach was associated with a posterolateral thoracotomy (n = 10) or a posterior midline approach (n = 4). In one patient, the procedure was achieved with a single posterolateral thoracotomy approach. An end-to-end anastomosis was performed in 16 patients. In one patient, a subclavian-left common carotid artery transposition was performed. In one other patient, an end-to-end anastomosis was performed between the proximal innominate artery and the SA. The right carotid artery was transposed into the SA in an end-to-side fashion. In 16 patients, prosthetic revascularization with a polytetrafluoroethylene graft was performed. Thirty-three patients underwent postoperative radiation therapy. Results: There were no cases of perioperative death, neurologic sequelae, graft infections or occlusions, or limb ischemia. There were two delayed asymptomatic polytetrafluoroethylene graft occlusions at 12 and 31 months. The 5-year patency rate was 85%. During this study, 20 patients died: 18 died of tumor recurrence (5 local and systemic and 13 systemic), one of respiratory failure, and one of an unknown cause at 74 months. The overall 5-year survival rate was 36%, and the 5-year disease-free survival rate was 18%. Conclusion: Tumor arterial invasion per se should not be a contraindication to TI cancer resection. This study shows that cancers that invade the SA can be resected through an L-shaped transclavicular cervicotomy, with good results with a concomitant revascularization of the SA. C1 Univ Paris Sud, Dept Thorac & Vasc Surg & Heart Lung Transplantat, Hop Marie Lannelongue, F-92350 Le Plessis Robinson, France. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Dartevelle, P (reprint author), Univ Paris Sud, Dept Thorac & Vasc Surg & Heart Lung Transplantat, Hop Marie Lannelongue, 133 Ave Resistance, F-92350 Le Plessis Robinson, France. RI Macchiarini, Paolo/E-6878-2013 NR 27 TC 6 Z9 7 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 1999 VL 29 IS 4 BP 581 EP 588 DI 10.1016/S0741-5214(99)70301-0 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 184TD UT WOS:000079628800001 PM 10194483 ER PT J AU Paillart, JC Gottlinger, HG AF Paillart, JC Gottlinger, HG TI Opposing effects of human immunodeficiency virus type 1 matrix mutations support a myristyl switch model of Gag membrane targeting SO JOURNAL OF VIROLOGY LA English DT Article ID ADP-RIBOSYLATION FACTOR-1; ENVELOPE GLYCOPROTEINS; NONDIVIDING CELLS; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; HIV-1 INFECTION; NUCLEAR IMPORT; AMINO-TERMINUS; PROTEIN; MYRISTOYLATION AB Targeting of the human immunodeficiency virus type 1 (HIV-1) Gag precursor Pr55(gag) to the plasma membrane, the site of virus assembly, is primarily mediated by the N-terminal matrix (MA) domain. N-myristylation of MA is essential for the stable association of Pr55(gag) With membranes and for virus assembly. We now show that single amino acid substitutions near the N terminus of MA can dramatically impair assembly without compromising myristylation. Subcellular fractionation demonstrated that Gag membrane binding was compromised to a similar extent as in the absence of the myristyl acceptor site, indicating that the myristyl group was not available for membrane insertion. Remarkably, the effects of the N-terminal modifications could be completely suppressed by second-site mutations in the globular core of MA. The compensatory mutations enhanced Gag membrane binding and increased viral particle yields above wild-type levels, consistent with an increase in the exposure of the myristyl group. Our results support a model in which the compact globular core of MA sequesters the myristyl group to prevent aberrant binding to intracellular membranes, while the N terminus is critical to allow the controlled exposure of the myristyl group for insertion into the plasma membrane. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gottlinger, HG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Heinrich_Gottlinger@DFCI.harvard.edu RI Paillart, Jean-Christophe/A-4171-2010 FU NIAID NIH HHS [P30 AI028691, AI28691, AI42510, R01 AI042510] NR 54 TC 119 Z9 120 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 2604 EP 2612 PG 9 WC Virology SC Virology GA 175XY UT WOS:000079122400005 PM 10074105 ER PT J AU Yang, XY Gabuzda, D AF Yang, XY Gabuzda, D TI Regulation of human immunodeficiency virus type 1 infectivity by the ERK mitogen-activated protein kinase signaling pathway SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; MAP KINASE; NEF PROTEIN; NUCLEAR-LOCALIZATION; MATRIX PROTEIN; INFECTED-CELLS; T-LYMPHOCYTES; DNA-SYNTHESIS; VPU-PROTEIN; IN-VITRO AB ERK1 and ERK2 mitogen-activated protein kinases (MAPK) play a critical role in regulation of cell proliferation and differentiation in response to mitogens and other extracellular stimuli. Mitogens and cytokines that activate MAPK in T cells have been shown to activate human immunodeficiency virus type 1 (HIV-1) replication, Little is known about the signal transduction pathways that activate HIV-1 replication in T cells upon activation by extracellular stimulation. Here, we report that activation of MAPK through the Ras/Raf/MEK signaling pathway enhances the infectivity of HIV-1 virions. Virus infectivity was enhanced by treatment of cells with MAPK stimulators, such as serum and phorbol myristate acetate, as well as by expression of constitutively activated Ras, Raf, or MEK (MAPK kinase) in the absence of extracellular stimulation. Treatment of cells with PD 098059, a specific inhibitor of MAPK activation, or with a MAPK antisense oligonucleotide reduced the infectivity of HIV-1 virions without significantly affecting virus production or the levels of virion-associated Gag and Env proteins. MAPK has been shown to regulate HIV-1 infectivity by phosphorylating Vif (X, Yang and D. Gabuzda, J. Biol. Chem, 273:29879-29887, 1998), However, MAPK activation enhanced virus infectivity in some cells lines that do not require Vif function. The HIV-1 Rev, Tat, p17(Gag), and Nef proteins were directly phosphorylated by MAPK in vitro, suggesting that other HIV-1 proteins are potential substrates for MAPK phosphorylation. These results suggest that activation of the ERK MAPK pathway plays a role in HIV-1 replication by enhancing the infectivity of HIV-1 virions through Vif-dependent as well as Vif-independent mechanisms. MAPK activation in producer cells may contribute to the activation of HIV-1 replication when T cells are activated by mitogens and other extracellular stimuli. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JF 712,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu FU NIAID NIH HHS [AI36186, AO6514, AI28691, P30 AI028691] NR 59 TC 98 Z9 99 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1999 VL 73 IS 4 BP 3460 EP 3466 PG 7 WC Virology SC Virology GA 175XY UT WOS:000079122400103 PM 10074203 ER PT J AU Jara, A Lee, E Stauber, D Moatamed, F Felsenfeld, AJ Kleeman, CR AF Jara, A Lee, E Stauber, D Moatamed, F Felsenfeld, AJ Kleeman, CR TI Phosphate depletion in the rat: Effect of bisphosphonates and the calcemic response to PTH SO KIDNEY INTERNATIONAL LA English DT Article DE bone; calcitriol; hypercalcemia; hypophosphatemia; osteoclast; calcium metabolism ID INHIBITS BONE LOSS; PARATHYROID-HORMONE; IN-VITRO; PRIMARY HYPERPARATHYROIDISM; PLASMA CALCIUM; RENAL-FAILURE; HYPOPHOSPHATEMIC RATS; SERUM-CALCIUM; D METABOLISM; RESORPTION AB Background. The removal of phosphate from the diet of the growing rat rapidly produces hypercalcemia, hypophosphatemia, hypercalciuria, and hypophosphaturia. Increased calcium efflux from bone has been shown to be the important cause of the hypercalcemia and hypercalciuria. It has been proposed that the increased calcium efflux from bone is osteoclast mediated. Because bisphosphonates have been shown to inhibit osteoclast-mediated bone resorption, this study was performed to determine whether bisphosphonate-induced inhibition of osteoclast function changed the biochemical and bone effects induced by phosphate depletion. Methods. Four groups of pair-fed rats were studied: (a) low-phosphate diet (LPD; phosphate less than 0.05%), (b) LPD plus the administration of the bisphosphonate Pamidronate (APD; LPD + APD), (c) normal diet (ND, 0.6% phosphate), and (d) ND + APD. All diets contained 0.6% calcium. A high dose of APD was administered subcutaneously (0.8 mg/kg) two days before the start of the study diet and on days 2, 6, and 9 during the 11 days of the study diet. On day 10, a 24-hour urine was collected, and on day 11, rats were either sacrificed or received an additional APD dose before a 48-hour parathyroid hormone (PTH) infusion (0.066 mu g/100 g/hr) via a subcutaneously implanted miniosmotic pump. Results. Serum and urinary calcium were greater in the LPD and LPD + APD groups than in the ND and ND + APD groups [serum, 11.12 +/- 0.34 and 11.57 +/- 0.45 vs. 9.49 +/- 0.17 and 9.48 +/- 0.15 mg/dl (mean +/- se), P < 0.05; and urine, 8.78 +/- 2.74 and 16.30 +/- 4.68 vs. 0.32 +/- 0.09 and 0.67 +/- 0.28 mg/24, hr, P < 0.05]. Serum PTH and serum and urinary phosphorus were less in the LPD and LPD + APD than in the ND and ND + APD groups (P < 0.05). The calcemic response to PTH was less (P < 0.05) in the LPD and LPD + APD groups than in the ND group and was less (P = 0.05) in the LPD + APD than in the ND + APD group. Bone histology showed that phosphate depletion increased the osteoblast and osteoclast surface, and treatment with APD reduced the osteoblast surface (LPD vs. LPD + APD, 38 +/- 4 vs. 4 +/- 2%, P < 0.05, and ND vs. ND + APD, 20 +/- 2 vs. 5 +/- 2%, P < 0.05) and markedly altered osteoclast morphology by inducing cytoplasmic vacuoles. Conclusions. (a) Phosphate depletion induced hypercalcemia and hypercalciuria that were not reduced by APD administration. (b) The calcemic response to PTH was reduced in phosphate-depleted rats and was unaffected by APD administration in normal and phosphate-depleted rats, and (c) APD administration markedly changed bone histology without affecting the biochemical changes induced by phosphate depletion. C1 W Los Angeles Vet Affairs Med Ctr, Div Nephrol, Nephrol Sect 111L, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Dept Pathol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Pontificia Univ Catolica Chile, Hosp Clin, Dept Nephrol, Santiago, Chile. RP Felsenfeld, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Nephrol, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM afelsenf@ucla.edu NR 64 TC 19 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 1999 VL 55 IS 4 BP 1434 EP 1443 DI 10.1046/j.1523-1755.1999.00395.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 177ZL UT WOS:000079240900028 PM 10201008 ER PT J AU Krolewski, AS AF Krolewski, AS TI Genetics of diabetic nephropathy: Evidence for major and minor gene effects SO KIDNEY INTERNATIONAL LA English DT Editorial Material DE diabetes mellitus; proteinuria; AT1 gene; ACE gene; angiotensinogen gene; heredity ID CONVERTING-ENZYME GENE; RENIN-ANGIOTENSIN SYSTEM; STAGE RENAL-DISEASE; CULTURED SKIN FIBROBLASTS; NA+/H+ ANTIPORT ACTIVITY; ESSENTIAL-HYPERTENSION; IDDM PATIENTS; IMMORTALIZED LYMPHOBLASTS; ACE GENE; FAMILIAL PREDISPOSITION C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK41526, DK53534] NR 96 TC 107 Z9 114 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD APR PY 1999 VL 55 IS 4 BP 1582 EP 1596 DI 10.1046/j.1523-1755.1999.00371.x PG 15 WC Urology & Nephrology SC Urology & Nephrology GA 177ZL UT WOS:000079240900048 PM 10201028 ER PT J AU Khan, T Havey, RM Sayers, ST Patwardhan, A King, WW AF Khan, T Havey, RM Sayers, ST Patwardhan, A King, WW TI Animal models of spinal cord contusion injuries SO LABORATORY ANIMAL SCIENCE LA English DT Article ID EVOKED-POTENTIALS; MOTOR CORTEX; RAT; DEVICE; VARIABILITY; CRITERIA; TRAUMA AB Background and Purpose: Traumatic spinal cord injury causes initial mechanical disruption of tissue, leading to a complex secondary sequence of pathophysiologic changes and neurologic impairment. These sequelae depend on the impact force delivered to the spinal cord at the time of injury. Successful clinical evaluation of the efficacy of any therapeutic regimen depends on the reliability and reproducibility of an experimental animal model. We describe a trauma device and the biomechanical parameters required to induce severe or moderate spinal cord contusion injury in cats and rats. Methods: Recovery after injury was determined by behavioral, electrophysiologic, and histologic evaluations, Results: Behavioral and electrophysiologic tests after injury clearly identified the experimental groups. A stable severe paraplegic state (defined as 6 months for cats and 8 weeks for rats), without evidence of behavioral or electrophysiologic recovery, was induced by a 65-Newton (N) load for cats and a 35-N load for rats, Moderate spinal cord contusion injury, from which cats and rats partially recovered after approximately 3 months and 4 weeks, respectively, was induced by a 45- and 25-N load, respectively. Conclusion: Use of these injury conditions provides reliable animal models for studies designed to evaluate potential therapeutic regimens for spinal cord injury. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Rehabil Res & Dev Ctr, Res Serv, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Mol & Cellular Biochem, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Orthoped & Rehabil, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. RP Khan, T (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Rehabil Res & Dev Ctr, Res Serv, POB 20, Hines, IL 60141 USA. NR 39 TC 31 Z9 56 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD APR PY 1999 VL 49 IS 2 BP 161 EP 172 PG 12 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 192MC UT WOS:000080082000008 PM 10331546 ER PT J AU Rattner, DW AF Rattner, DW TI Future directions in innovative minimally invasive surgery SO LANCET LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Gen Surg, Partners Ctr Innovat Minimally Invas Therapy, Boston, MA 02114 USA. RP Rattner, DW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Gen Surg, Partners Ctr Innovat Minimally Invas Therapy, Boston, MA 02114 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR PY 1999 VL 353 SU 1 BP SL12 EP SL15 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 192NH UT WOS:000080084900006 ER PT J AU Bloch, DB Gutierrez, JA Guerriero, V Bloch, KJ AF Bloch, DB Gutierrez, JA Guerriero, V Bloch, KJ TI Recognition of a dominant epitope in bovine heat-shock protein 70 in inner ear disease SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 21st Midwinter Research Meeting of the Association-for-Research-in-Otolaryngology CY FEB 15-19, 1998 CL ST PETERSBURG BEACH, FLORIDA SP Assoc Res Otolaryngol ID SENSORINEURAL HEARING-LOSS; HUMAN HSP70; SERUM ANTIBODIES; MENIERES-DISEASE; T-CELLS; HEAT-SHOCK-PROTEIN-70; AUTOANTIBODIES; MYCOBACTERIAL; SEQUENCE; ANTIGEN AB Objective: To investigate the specificity of antibodies to heat-shock protein 70 (HSP70) in patients with idiopathic, progressive, bilateral sensorineural hearing loss (IPBSNHL) and Meniere disease. Study Design: Test immunoreactivity of patients' sera using recombinant human (rh) and bovine (rb) HSP70, as well as segments representing different regions of bovine HSP70 as antigen. Methods: Sera were tested by Western blotting. Results: Of 52 patients with IPB-SNHL, 40 sera reacted only with rbHSP70; 12 reacted with both rbHSP70 and rhHSP70. Sera from 13 patients with IPBSNHL and from 8 with Meniere disease were tested on the panel of bovine HSP70 segments. Eleven and 7 samples, respectively, reacted with amino acid segment 427-461 from the carboxy (C)-terminal region of the molecule. Conclusion: In IPBSNHL and Meniere disease, antibodies are directed primarily against an epitope(s) within the C-terminal region of HSP70 where diversity in sequence among different species, including possible pathogens, is greatest. These findings may provide clues to the pathogenesis or specific serodiagnosis (or both) of diseases of the inner ear. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Med Serv, Arthrit Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Serv, Allergy & Clin Immunol Unit, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Arizona, Dept Anim Sci, Tucson, AZ 85721 USA. RP Bloch, KJ (reprint author), Massachusetts Gen Hosp, Clin Immunol Unit, 55 Fruit St,Bulfinch 422, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC02831] NR 28 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 1999 VL 109 IS 4 BP 621 EP 625 DI 10.1097/00005537-199904000-00019 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 183EM UT WOS:000079541100019 PM 10201752 ER PT J AU Rasmussen, RA Sharma, PL Hu, Y Ruprecht, RM AF Rasmussen, RA Sharma, PL Hu, Y Ruprecht, RM TI Vaccine protection by subinfectious doses of a live murine leukemia virus SO LEUKEMIA LA English DT Article; Proceedings Paper CT XIX Symposium of the International-Association-for-Comparative-Research-on-Leukemia-and-Relat ed-Diseases CY JUL 12-18, 1997 CL MANNHEIM, GERMANY SP Int Assoc Comparat Res Leukemia & Related Dis ID IMMUNITY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Viral Pathogenesis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Rasmussen, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Lab Viral Pathogenesis, 44 Binney St, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 1999 VL 13 SU 1 BP S94 EP S95 DI 10.1038/sj.leu.2401320 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 197GA UT WOS:000080356000021 PM 10232377 ER PT J AU Duerinckx, AJ Yu, WD El-Saden, S Kim, D Wang, JC Sandhu, HS AF Duerinckx, AJ Yu, WD El-Saden, S Kim, D Wang, JC Sandhu, HS TI MR imaging of cervical spine motion with haste SO MAGNETIC RESONANCE IMAGING LA English DT Article DE cervical spine; kinematics; cardiac triggering; Turbo or fast spin-echo; HASTE; dynamic MRI ID FLEXION-EXTENSION; PATELLAR TRACKING; RHEUMATOID-ARTHRITIS; ABNORMALITIES; ROTATION; SHOULDER; JOINT AB The HASTE (half-Fourier acquisition single-shot turbo spin-echo) technique delivers images with T2-weighting in about half a second and could be ideal for fast dynamic studies when T2-weighting is needed, We evaluated cardiac-triggered HASTE to study cervical spine flexion/extension, The cervical spines of ten asymptomatic volunteers were studied during flexion/extension motion on a 1.5 Tesla imager using a cardiac triggered version of the HASTE technique. Midline sagittal images were acquired every 2 to 3 s during neck flexion and extension. Image quality was compared to traditional T2-weighted Turbo spin-echo. The study duration per flexion/extension was typically less than 20 seconds and well tolerated. The cardiac-gated T2-weighted HASTE images compared favorably to the traditional T2-weighted TSE images in quality and overall anatomic detail. Range of motion averaged: flexion 30 degrees (range 8 degrees-48 degrees) and extension 23 degrees (range 0 degrees-57 degrees), Greatest motion occurred in the lower cervical spine (C4-C7), At the intervertebral discs the canal diameter, anterior and posterior CSF spaces were widest in neutral position and decreased with flexion and extension. Therefore, Cardiac-gated T2 HASTE sequences provide diagnostic and time-efficient dynamic MR images of cervical spine motion, (C) 1999 Elsevier Science Inc. C1 W Los Angeles Vet Affairs Med Ctr, Serv Radiol, Los Angeles, CA 90073 USA. RP Duerinckx, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Serv Radiol, 11301 Wilshire Blvd,MR1,Bld 507,Mail Route W114, Los Angeles, CA 90073 USA. EM ajd@ucla.edu NR 40 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD APR PY 1999 VL 17 IS 3 BP 371 EP 381 DI 10.1016/S0730-725X(98)00176-3 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 178VZ UT WOS:000079291000006 PM 10195580 ER PT J AU Florell, SR Bruggers, CS Matlak, M Young, RH Lowichik, A AF Florell, SR Bruggers, CS Matlak, M Young, RH Lowichik, A TI Ovarian small cell carcinoma of the hypercalcemic type in a 14 month old: The youngest reported case SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE small cell carcinoma; ovary; ovarian neoplasms; hypercalcemia; pamidronate; child ID CHEMOTHERAPY C1 Primary Childrens Med Ctr, Dept Pediat Oncol, Salt Lake City, UT 84113 USA. Primary Childrens Med Ctr, Huntsman Canc Inst, Ctr Children, Salt Lake City, UT 84113 USA. Univ Utah, Hlth Sci Ctr, Dept Pathol, Salt Lake City, UT 84132 USA. Primary Childrens Med Ctr, Dept Pediat Surg, Salt Lake City, UT 84113 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Lowichik, A (reprint author), Primary Childrens Med Ctr, Dept Pathol, 100 N Med Dr, Salt Lake City, UT 84113 USA. NR 7 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD APR PY 1999 VL 32 IS 4 BP 304 EP 307 DI 10.1002/(SICI)1096-911X(199904)32:4<304::AID-MPO13>3.0.CO;2-M PG 4 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 178MD UT WOS:000079269000015 PM 10102028 ER PT J AU Barnett, PG AF Barnett, PG TI Review of methods to determine VA health care costs SO MEDICAL CARE LA English DT Article DE hospitals; veterans; economics; health care costs; costs and cost analysis; methods ID MULTIVARIATE PREDICTION MODEL; HOME CARE; RAPID ESTIMATION; VETERANS; HOSPITALIZATION; EXPERIENCE; MANAGEMENT; OUTCOMES; PROGRAMS; CHARGES AB BACKGROUND. Estimates of health care cost are needed to conduct cost-effectiveness research at the facilities operated by the US Department of Veterans Affairs. METHODS. The medical literature was searched for VA studies to characterize different cost methods and identify their advantages and disadvantages. RESULTS. Different methods are appropriate for different studies. Analysts who wish to capture the effect of an intervention on resources used in a health care encounter may wish to create a detailed pseudo-bill by combining VA utilization data with unit costs from the non-VA sector. If a cost function can be estimated from non-VA data, VA costs may be determined more economically from a reduced list of utilization items. If the analysis involves a new intervention or a program that is unique to VA, direct measurement of staff time and supplies may be needed. It is often sufficient to estimate the average cost of similar encounters, for example, the average of all hospital stays with the same diagnosis and same length of stay. Such estimates may be made by combining VA cost and utilization data bases and by applying judicious assumptions. CONCLUSIONS. Assumptions used to estimate costs need to be documented and tested. VA cost-effectiveness research could be facilitated by the creation of a universal cost data base; however, it will not supplant the detailed estimates that are needed to determine the effect of clinical interventions on cost. C1 US Dept Vet Affairs, Hlth Serv Res & Dev Field Program, Menlo Park, CA USA. US Dept Vet Affairs, Cooperat Studies Program, Menlo Park, CA USA. Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Barnett, PG (reprint author), VA Palo Alto Hlth Care Syst, HSR&D Ctr Hlth Care Evaluat, 795 Willow Rd,152 MPD, Menlo Park, CA 94025 USA. NR 40 TC 35 Z9 35 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 1999 VL 37 IS 4 SU VA BP AS9 EP AS17 DI 10.1097/00005650-199904002-00003 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 188PQ UT WOS:000079857500003 PM 10217380 ER PT J AU Barnett, PG Rodgers, JH AF Barnett, PG Rodgers, JH TI Use of the Decision Support System for VA cost-effectiveness research SO MEDICAL CARE LA English DT Article DE hospitals; veterans; economics; health care costs; costs and cost analysis; methods AB BACKGROUND. The Department of Veterans Affairs is adopting the Decision Support System (DSS), computer software and databases which include a cost-accounting system which determines the cost of health care products and patient encounters. OBJECTIVES. A system for providing cost data for cost-effectiveness analysis should be provide valid, detailed, and comprehensive data that can be aggregated. METHODS, The design of DSS is described and compared with those criteria. Utilization data from DSS was compared with other VA utilization data. Aggregate DSS cost data from 35 medical centers was compared with relative resource weights developed for the Medicare program. RESULTS. Data on hospital stays at 3 facilities found that 3.7% of the stays in DSS were not in the VA discharge database, whereas 7.6% of the stays in the discharge data were not in DSS. DSS reported between 68.8% and 97.1% of the outpatient encounters reported by six facilities in the ambulatory care data base. Relative weights for each Diagnosis Related Group based on DSS data from 35 VA facilities correlated with Medicare weights (correlation coefficient of .853). CONCLUSIONS. DSS will be useful for research if certain problems are overcome. It is difficult to distinguish long-term from acute hospital care. VA does not have a complete database of all inpatient procedures, so DSS has not assigned them a specific cost. The authority to access encounter-level DSS data needs to be centralized. Researchers can provide the feedback needed to improve DSS cost estimates. A comprehensive encounter-level extract would facilitate use of DSS for research. C1 US Dept Vet Affairs, Hlth Serv Res & Dev Field Program, Menlo Park, CA USA. US Dept Vet Affairs, Ctr Cooperat Studies, Menlo Park, CA USA. Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Barnett, PG (reprint author), VA Palo Alto Hlth Care Syst, HSR&D Ctr Hlth Care Evaluat, 795 Willow Rd,152 MPD, Menlo Park, CA 94025 USA. NR 6 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 1999 VL 37 IS 4 SU VA BP AS63 EP AS70 DI 10.1097/00005650-199904002-00009 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 188PQ UT WOS:000079857500009 PM 10217386 ER PT J AU Chapko, MK Hedrick, S AF Chapko, MK Hedrick, S TI Cost as a study outcome - Sensitivity of study conclusions to the method of estimating cost SO MEDICAL CARE LA English DT Article DE hospital cost; long-term care cost; ambulatory care cost; Department of Veterans Affairs ID RANDOMIZED CLINICAL-TRIAL; HEALTH-CARE EVALUATION; HOME CARE; VETERANS; PROGRAMS AB OBJECTIVES. The analyses presented here are intended to provide empirical guidance to two questions faced by researchers performing clinical trials which include a cost component: Which health care services should we track? Should we use facility specific costs or national average costs for individual services in estimating total costs? METHODS. We reanalyzed cost data from the Department of Veterans Affairs (VA) multisite clinical trial which compared Adult Day Health Care (ADHC) to Customary Care for patients at high risk for nursing home care. The data presented here compares the original analysis (a combination of local and national costs) to an analysis based on purely facility-specific costs and to an analysis based upon purely VA national costs, Costs for hospital, clinic, nursing home, ADHC, hospital based home care, rehabilitation, pharmacy, and laboratory were included. RESULTS. Hospital, nursing home, clinic, and ADHC in combination account for 98% of the variation in total cost per patient. Including only hospital, clinic, nursing home, ADHC, and hospital-based home care in total cost per patient closely replicated the findings for total cost when ail services were included. The originally reported analysis and the 2 new analyses, using respectively facility specific costs and national average costs, did differ substantially in the magnitude of the difference between the total cost per patient of ADHC and Customary Care. They did differ with regard to statistical significance as the P values were either slightly above or below 0.05. CONCLUSIONS. ideally all health care costs should be included in the analysis. When this is not feasible, one should determine utilization and cost for the intervention itself, costly services (usually hospital, nursing home, and clinic care), and lower cost services that are likely to be affected by the intervention. Sensitivity analysis should be performed to determine if different methods of costing (eg, facility specific versus national costs) materially affect the conclusions of the study. C1 VA Puget Sound, Hlth Care Syst, Hlth Serv Res & Dev, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. RP Chapko, MK (reprint author), VA Puget Sound, Hlth Care Syst, Hlth Serv Res & Dev, Seattle Div, 152,1660 S Columbian Way, Seattle, WA 98108 USA. NR 22 TC 8 Z9 8 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 1999 VL 37 IS 4 SU VA BP AS37 EP AS44 DI 10.1097/00005650-199904002-00006 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 188PQ UT WOS:000079857500006 PM 10217383 ER PT J AU Margossian, SS Anderson, PAW Chantler, PD Deziel, M Umeda, PK Patel, H Stafford, WF Norton, P Malhotra, A Yang, F Caulfield, JB Slayter, HS AF Margossian, SS Anderson, PAW Chantler, PD Deziel, M Umeda, PK Patel, H Stafford, WF Norton, P Malhotra, A Yang, F Caulfield, JB Slayter, HS TI Calcium regulation in the human myocardium affected by dilated cardiomyopathy: A structural basis for impaired Ca2+-sensitivity SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE ATPase activity; cardiomyopathy; heart failure; myosin light chains; troponin-tropomyosin; mekratin ID CARDIAC TROPONIN-T; MYOFIBRILLAR ATPASE ACTIVITY; SKELETAL-MUSCLE FIBERS; MYOSIN LIGHT-CHAINS; HYPERTROPHIC CARDIOMYOPATHY; SCALLOP MYOSIN; FAILING HEART; THIN FILAMENT; SEQUENCE COMPARISONS; ISOFORM EXPRESSION AB Calcium regulation in the human heart is impaired during idiopathic dilated cardiomyopathy (IDC). Here, we analyze the structural basis for impairment in the regulatory mechanism. Regulation of contractility was monitored by MgATPase and Ca2+-binding assays as a function of calcium. Myofibrillar proteolysis and expression of troponin T isoforms were established by gel electrophoresis and by Western blots. Myofibrillar ATPase assays in low salt however, revealed a drastic lowering of calcium sensitivity in IDC myofibrils as indicated by reductions in both activation by high calcium and in EGTA-mediated inhibition of MgATPase. Structural changes in myofilament proteins were found in most IDC hearts, specifically proteolysis of myosin light chain 2 (LC2), troponin T and I (TnT and TnI), and sometimes large isoform shift in TnT. IDC did not induce mutations in LC2 and troponin C (TnC), as established by cDNA sequence data from IDC cases, thus, calcium binding to IDC myofibrils was unaffected. Reassociation of IDC myofibrils with native LC2 raised MgATPase activation at high Ca2+ to control levels, while repletion with intact, canine TnI/TnT restored inhibition at low Ca2+. A model, identifying possible steps in the steric blocking mechanism of regulation, is proposed to explain IDC-induced changes in Ca2+-regulation. Moreover, shifts in TnT isoforms may imply either a genetic or a compensatory factor in the development and pathogenesis of some forms of IDC. C1 Albany Med Coll, Dept Med & Biochem & Mol Biol, Albany, NY 12208 USA. Duke Univ, Med Ctr, Div Pediat Cardiol, Durham, NC USA. Univ London Royal Vet Coll, Dept Vet Basic Sci, London, England. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Boston Biomed Res Inst, Boston, MA USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. Albany Med Coll, Dept Pathol, Albany, NY 12208 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Margossian, SS (reprint author), Ferrahian Armenian Sch, 5300 White Oak Ave, Encino, CA 91316 USA. FU NHLBI NIH HHS [HL20749, HL44094, HL49597]; Wellcome Trust NR 62 TC 11 Z9 11 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 1999 VL 194 IS 1-2 BP 301 EP 313 DI 10.1023/A:1006980405359 PG 13 WC Cell Biology SC Cell Biology GA 202GP UT WOS:000080644200036 PM 10391153 ER PT J AU Huang, YY Nakada, S Ishiko, T Utsugisawa, T Datta, R Kharbanda, S Yoshida, K Talanian, RV Weichselbaum, R Kufe, D Yuan, ZM AF Huang, YY Nakada, S Ishiko, T Utsugisawa, T Datta, R Kharbanda, S Yoshida, K Talanian, RV Weichselbaum, R Kufe, D Yuan, ZM TI Role for caspase-mediated cleavage of Rad51 in induction of apoptosis by DNA damage SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ABL TYROSINE KINASE; ICE-LIKE PROTEASE; ESCHERICHIA-COLI RECA; CYTOCHROME-C; CELL-DEATH; POLY(ADP-RIBOSE) POLYMERASE; HOMOLOGOUS RECOMBINATION; PROTEOLYTIC ACTIVATION; IONIZING-RADIATION AB We report here that the Rad51 recombinase is cleaved in mammalian cells during the induction of apoptosis by ionizing radiation (IR) exposure, The results demonstrate that IR induces Rad51 cleavage by a caspase-dependent mechanism, Further support for involvement of caspases is provided by the finding that IR-induced proteolysis of Rad51 is inhibited by Ac-DEVD-CHO. In vitro studies show that Rad51 is cleaved by caspase 3 at a DVLD/N site. Stable expression of a Rad51 mutant in which the aspartic acid residues were mutated to alanines (AVLA/N) confirmed that the DVLD/N site is responsible for the cleavage of Rad51 in IR-induced apoptosis. The functional significance of Rad51 proteolysis is supported by the finding that, unlike intact Rad51, the N- and C-terminal cleavage products fail to exhibit recombinase activity. In cells, overexpression of the Rad51 (D-A) mutant had no effect on activation of caspase 3 but did abrogate in Dart the apoptotic response to IR exposure. We conclude that proteolytic inactivation of Rad51 by a caspase-mediated mechanism contributes to the cell death response induced by DNA damage. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. BASF Biores Corp, Worcester, MA 01605 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA55241] NR 81 TC 68 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1999 VL 19 IS 4 BP 2986 EP 2997 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 178MG UT WOS:000079269300058 PM 10082566 ER PT J AU Steen, SB Han, JO Mundy, C Oettinger, MA Roth, DB AF Steen, SB Han, JO Mundy, C Oettinger, MA Roth, DB TI Roles of the "dispensable" portions of RAG-1 and RAG-2 in V(D)J recombination SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BROKEN DNA-MOLECULES; DOUBLE-STRAND BREAKS; CELL-CYCLE; SIGNAL SEQUENCES; MOUSE THYMOCYTES; MU-TRANSPOSASE; CODING ENDS; B-CELLS; IN-VIVO; INITIATION AB V(D)J recombination is initiated by introduction of site-specific double-stranded DNA breaks by the RAG-1 and RAG-2 proteins. The broken DNA ends are then joined by the cellular double-strand break repair machinery. Previous work has shown that truncated (core) versions of the RAG proteins can catalyze V(D)J recombination, although less efficiently than their full-length counterparts. It is not known whether truncating RAG-1 and/or RAG-2 affects the cleavage step or the joining step of recombination. Here we examine the effects of truncated RAG proteins on recombination intermediates and products. We found that while truncated RAG proteins generate lower levels of recombination products than their full-length counterparts, they consistently generate 10-fold higher levels of one class of recombination intermediates, termed signal ends. Our results suggest that this increase in signal ends does not result from increased cleavage, since levels of the corresponding intermediates, coding ends, are not elevated. Thus, removal of the "dispensable" regions of the RAG proteins impairs proper processing of recombination intermediates. Furthermore, we found that removal of portions of the dispensable regions of RAG-1 and RAG-2 affects the efficiency of product formation without altering the levels of recombination intermediates. Thus, these evolutionarily conserved sequences play multiple, important roles in V(D)J recombination. C1 Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. Baylor Coll Med, Cell & Mol Biol Program, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Roth, DB (reprint author), Baylor Coll Med, Howard Hughes Med Inst, Immunol M929 DeBakey Bldg,1 Baylor Plaza, Houston, TX 77030 USA. EM davidbr@bcm.tmc.edu FU NIAID NIH HHS [AI-36420, R01 AI036420, T32-AI07495, T32 AI007495] NR 41 TC 63 Z9 65 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1999 VL 19 IS 4 BP 3010 EP 3017 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 178MG UT WOS:000079269300060 PM 10082568 ER PT J AU Liu, LQ Ilaria, R Kingsley, PD Iwama, A Van Etten, RA Palis, J Zhang, DE AF Liu, LQ Ilaria, R Kingsley, PD Iwama, A Van Etten, RA Palis, J Zhang, DE TI A novel ubiquitin-specific protease, UBP43, cloned from leukemia fusion protein AML1-ETO-expressing mice, functions in hematopoietic cell differentiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FAT-FACETS GENE; DEUBIQUITINATING ENZYME; SACCHAROMYCES-CEREVISIAE; RETROVIRAL VECTORS; MYELOID-LEUKEMIA; DEGRADATION; LINE; EXPRESSION; PROMOTER; FAMILY AB Using PCR-coupled subtractive screening-representational difference analysis, we have cloned a novel gene from AML1-ETO knockin mice. This gene is highly expressed in the yolk sac and fetal liver of the knockin mice. Nucleotide sequence analysis indicates that its cDNA contains an 1,107-bp open reading frame encoding a 368-amino-acid polypeptide. Further protein sequence and protein translation analysis shows that it belongs to a family of ubiquitin-specific proteases (UBP), and its molecular mass is 43 kDa, Therefore, we have named this gene UBP43, Like other ubiquitin proteases, the UBP43 protein has deubiquitinating enzyme activity. Protein ubiquitination has been implicated in many important cellular events. In wild-type adult mice, UBP43 is highly expressed in the thymus and in peritoneal macrophages. Among nine different murine hematopoietic cell lines analyzed, UBP43 expression is detectable only in cell lines related to the monocytic lineage. Furthermore, its expression is regulated during cytokine induced monocytic cell differentiation, We have investigated its function in the hematopoietic myeloid cell line M1, UBP43 was introduced into M1 cells by retroviral gene transfer, and several high-expressing UBP43 clones were obtained for further study. Morphologic and cell surface marker examination of UBP43/M1 cells reveals that overexpression of UBP43 blocks cytokine-induced terminal differentiation of monocytic cells. These data suggest that UBP43 plays an important role in hematopoiesis by modulating either the ubiquitin-dependent proteolytic pathway or the ubiquitination state of another regulatory factor(s) during myeloid cell differentiation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Rochester, Ctr Canc, Rochester, NY 14642 USA. RP Zhang, DE (reprint author), Harvard Univ, Inst Med, HIM 953,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA072009, CA/72009, CA/AI59589]; NHLBI NIH HHS [HL 59484-01, R01 HL059484] NR 54 TC 96 Z9 100 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1999 VL 19 IS 4 BP 3029 EP 3038 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 178MG UT WOS:000079269300062 PM 10082570 ER PT J AU Kophengnavong, T Carroll, AS Blackwell, TK AF Kophengnavong, T Carroll, AS Blackwell, TK TI The SKN-1 amino-terminal arm is a DNA specificity segment SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID C-ELEGANS EMBRYOS; CRYSTAL-STRUCTURE; LEUCINE-ZIPPER; BASIC REGION; BINDING DOMAIN; HOMEODOMAIN; COMPLEX; PROTEIN; RECOGNITION; BEND AB The Caenorhabditis elegans SKN-1 protein binds DNA through a basic region like those of bZIP proteins and through a flexible amino-terminal arm segment similar to those with which numerous helix-turn-helix proteins bind to bases in the minor groove. A recent X-ray crystallographic structure suggests that the SKN-1 aminoterminal arm provides only nonspecific DNA binding. In this study, however, we demonstrate that this segment mediates recognition of an AT-rich element that is part of the preferred SKN-1 binding site and thereby significantly increases the sequence specificity with which SKN-1 binds DNA. Mutagenesis experiments show that multiple amino acid residues within the arm are involved in binding. These residues provide binding affinity through distinct but partially redundant interactions and enhance specificity by discriminating against alternate sites. The AT-rich element minor groove is important for binding of the arm, which appears to affect DNA conformation in this region. This conformational effect does not seem to involve DNA bending, however, because the arm does not appear to affect a modest DNA bend that is induced by SKN-1. The data illustrate an example of how a small, flexible protein segment can make an important contribution to DNA binding specificity through multiple interactions and mechanisms. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM50900] NR 49 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1999 VL 19 IS 4 BP 3039 EP 3050 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 178MG UT WOS:000079269300063 PM 10082571 ER PT J AU Harada, H Becknell, B Wilm, M Mann, M Huang, LJS Taylor, SS Scott, JD Korsmeyer, SJ AF Harada, H Becknell, B Wilm, M Mann, M Huang, LJS Taylor, SS Scott, JD Korsmeyer, SJ TI Phosphorylation and inactivation of BAD by mitochondria-anchored protein kinase A SO MOLECULAR CELL LA English DT Article ID PROGRAMMED CELL-DEATH; COLONY-STIMULATING FACTOR; BCL-X-L; BH3 DOMAIN; CYTOCHROME-C; IN-VIVO; APOPTOSIS; SURVIVAL; ACTIVATION; AKT AB Signaling pathways between cell surface receptors and the BCL-2 family of proteins regulate cell death. Survival factors induce the phosphorylation and inactivation of BAD, a proapoptotic member. Purification of BAD kinase(s) identified membrane-based cAMP-dependent protein kinase (PKA) as a BAD Ser-112 (S112) site-specific kinase. PKA-specific inhibitors blocked the IL-3-induced phosphorylation on S112 of endogenous BAD as well as mitochondria-based BAD S112 kinase activity. A blocking peptide that disrupts type II PKA holoenzyme association with A-kinase-anchoring proteins (AKAPs) also inhibited BAD phosphorylation and eliminated the BAD S112 kinase activity at mitochondria. Thus, the anchoring of PKA to mitochondria represents a focused subcellular kinase/substrate interaction that inactivates BAD at its target organelle in response to a survival factor. C1 Washington Univ, Sch Med, Howard Hughes Med Inst, Div Mol Oncol, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Vollum Inst, Howard Hughes Med Inst, Portland, OR 97201 USA. EMBL, Prot & Peptide Grp, Heidelberg, Germany. Univ Calif San Diego, Sch Med, Dept Chem & Biochem, Howard Hughes Med Inst, La Jolla, CA 92093 USA. RP Korsmeyer, SJ (reprint author), Washington Univ, Sch Med, Howard Hughes Med Inst, Div Mol Oncol, St Louis, MO 63110 USA. RI Mann, Matthias/A-3454-2013 OI Mann, Matthias/0000-0003-1292-4799 FU NCI NIH HHS [5R01 CA 50239-10] NR 53 TC 490 Z9 507 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD APR PY 1999 VL 3 IS 4 BP 413 EP 422 DI 10.1016/S1097-2765(00)80469-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 190VV UT WOS:000079986700001 PM 10230394 ER PT J AU Defossez, PA Prusty, R Kaeberlein, M Lin, SJ Ferrigno, P Silver, PA Keil, RL Guarente, L AF Defossez, PA Prusty, R Kaeberlein, M Lin, SJ Ferrigno, P Silver, PA Keil, RL Guarente, L TI Elimination of replication block protein Fob1 extends the life span of yeast mother cells SO MOLECULAR CELL LA English DT Article ID RIBOSOMAL-RNA GENES; SACCHAROMYCES-CEREVISIAE; CAENORHABDITIS-ELEGANS; DNA-REPLICATION; FORK BLOCKING; FAMILY MEMBER; POLYMERASE-I; 3' END; TRANSCRIPTION; RECOMBINATION AB A cause of aging in yeast is the accumulation of circular species of ribosomal DNA (rDNA) arising from the 100-200 tandemly repeated copies in the genome. We show here that mutation of the FOB1 gene slows the generation of these circles and thus extends life span. Fob1p is known to create a unidirectional block to replication forks in the rDNA. We show that Fob1p is a nucleolar protein, suggesting a direct involvement in the replication fork block. We propose that this block can trigger aging by causing chromosomal breaks, the repair of which results in the generation of rDNA circles. These findings may provide a novel link between metabolic rate and aging in yeast and, perhaps, higher organisms. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Guarente, L (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. OI Kaeberlein, Matt/0000-0002-1311-3421 NR 49 TC 242 Z9 244 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD APR PY 1999 VL 3 IS 4 BP 447 EP 455 DI 10.1016/S1097-2765(00)80472-4 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 190VV UT WOS:000079986700004 PM 10230397 ER PT J AU Auger, KJ Ajene, A Lerner, T AF Auger, KJ Ajene, A Lerner, T TI Progress toward the cloning of CLN6, the gene underlying a variant LINCL SO MOLECULAR GENETICS AND METABOLISM LA English DT Article; Proceedings Paper CT 7th International Congress on the Neuronal Ceroid-Lipofuscinoses (NCL-98) CY JUN 13-16, 1998 CL DALLAS, TEXAS DE variant LINCL; Costa Rica; gene cloning ID NEURONAL CEROID-LIPOFUSCINOSIS; BATTEN DISEASE; HUMAN GENOME; LOCI; PROTEIN; MAP; ASSOCIATION; MUTATIONS AB Marked clinical heterogeneity is seen in the late-infantile subtype of NCL (LINCL), complicating genetic analysis. In addition to the classical subtype, encoded by CLN2 on chromosome 11p15.5, several variant subtypes have also been described. In this paper, we report our progress in cloning a variant LINCL gene mapped in a small group of Costa Rican families. Clinically, these patients appear similar to classical LINCL patients, except onset of the disease is delayed and the course is milder, Extended haplotype analysis confirms the localization of this gene to chromosome 15q21-22, where CLN6 has also been mapped. Using now-standard positional cloning techniques, we have developed a physical map of our candidate region. These clones have been used to order genetic markers, STSs, and ESTs in this region and will be used for the identification of the disease gene transcript, (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02112 USA. RP Lerner, T (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS33648] NR 20 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 1999 VL 66 IS 4 BP 332 EP 336 DI 10.1006/mgme.1999.2805 PG 5 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 190BJ UT WOS:000079941400020 PM 10191124 ER PT J AU Li, YZ Li, CJ Pinto, AV Pardee, AB AF Li, YZ Li, CJ Pinto, AV Pardee, AB TI Release of mitochondrial cytochrome C in both apoptosis and necrosis induced by beta-lapachone in human carcinoma cells SO MOLECULAR MEDICINE LA English DT Article ID PROSTATE-CANCER CELLS; INDUCTION; CASPASE-3; PROTEASE; DEATH AB Background: There are two fundamental forms of cell death: apoptosis and necrosis. Molecular studies of cell death thus far favor a model in which apoptosis and necrosis share very few molecular regulators. It appears that apoptotic processes triggered by a variety of stimuli converge on the activation of a member of the caspase family, such as caspase 3, which leads to the execution of apoptosis. It has been suggested that blocking of caspase activation in an apoptotic process may divert cell death to a necrotic demise, suggesting that apoptosis and necrosis may share some upstream events. Activation of caspase is preceded by the release of mitochondrial cytochrome C. Materials and Methods: We first studied cell death induced by beta-lapachone by MTT and colony-formation assay. To determine whether the cell death induced by beta-lapachone occurs through necrosis or apoptosis, we used the PI staining procedure to determine the sub-G1 fraction and the Annexin-V staining for externalization of phophatidylserine. We next compared the release of mitochondrial cytochrome C in apoptosis and necrosis. Mitochondrial cytochrome C was determined by Western blot analysis. To investigate changes in mitochondria that resulted in cytochrome C release, the mitochondrial membrane potential (delta psi) was analyzed by the accumulation of rhodamine 123, a membrane-permeant cationic fluorescent dye. The activation of caspase in apoptosis and necrosis were measured by using a profluorescent substrate for caspase-like proteases, PhiPhiLuxG6D2. Results: beta-lapachone induced cell death in a spectrum of human carcinoma cells, including nonproliferating cells. It induced apoptosis in human ovary, colon, and lung cancer cells, and necrotic cell death in four human breast cancer cell lines. Mitochondrial cytochrome C release was found in both apoptosis and necrosis. This cytochrome C release occurred shortly after beta-lapachone treatment when cells were fully viable by trypan blue exclusion and MTT assay, suggesting that cytochrome C release is an early event in beta-lapachone induced apoptosis as well as necrosis. The mitochondrial cytochrome C release induced by beta-lapachone is associated with a decrease in mitochondrial transmembrane potential (delta psi). There was activation of caspase 3 in apoptotic cell death, but not in necrotic cell death. This lack of activation of CPP 32 in human breast cancer cells is consistent with the necrotic cell death induced by beta-lapachone as determined by absence of sub-G1 fraction, externalization of phosphatidylserine. Conclusions: beta-lapachone induces either apoptotic or necrotic cell death in a variety of human carcinoma cells including ovary, colon, lung, prostate, and breast, suggesting a wide spectrum of anti-cancer activity in vitro. Both apoptotic and necrotic cell death induced by beta-lapachone are preceded by a rapid release of cytochrome C, followed by the activation of caspase 3 in apoptotic cell death but not in necrotic cell death. Our results suggest that beta-lapachone is a potential anti-cancer drug acting on the mitochondrial cytochrome C-caspase pathway, and that cytochrome C is involved in the early phase of necrosis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cell Growth & Regulat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Ctr Ciencias Dasaude, BR-21941590 Rio De Janeiro, Brazil. RP Li, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cell Growth & Regulat, D612,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01CA61253] NR 16 TC 97 Z9 99 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD APR PY 1999 VL 5 IS 4 BP 232 EP 239 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 205TV UT WOS:000080837400003 PM 10448645 ER PT J AU Weissleder, R Tung, CH Mahmood, U Bogdanov, A AF Weissleder, R Tung, CH Mahmood, U Bogdanov, A TI In vivo imaging of tumors with protease-activated near-infrared fluorescent probes SO NATURE BIOTECHNOLOGY LA English DT Article DE optical imaging; tumor targeting; proteases ID MATRIX METALLOPROTEINASE INHIBITORS; CATHEPSIN-B; SERINE PROTEASES; BREAST-CANCER; EXPRESSION; PROGRESSION; DELIVERY; MMP-9; DERIVATIVES; MEDICINE AB We have developed a method to image tumor-associated lysosomal protease activity in a xenograft mouse model in vivo using autoquenched near-infrared fluorescence (NIRF) probes. NIRF probes were bound to a long circulating graft copolymer consisting of poly-L-lysine and methoxypolyethylene glycol succinate. Following intravenous injection, the NIRF probe carrier accumulated in solid tumors due to its long circulation time and leakage through tumor neovasculature. Intratumoral NIRF signal was generated by lysosomal proteases in tumor cells that cleave the macromolecule, thereby releasing previously quenched fluorochrome. In vivo imaging showed a 12-fold increase in NIRF signal, allowing the detection of tumors with submillimeter-sized diameters. This strategy can be used to detect such early stage tumors in vivo and to probe for specific enzyme activity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. EM weissleder@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R01 CA74424-01] NR 55 TC 1100 Z9 1120 U1 28 U2 274 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 1999 VL 17 IS 4 BP 375 EP 378 DI 10.1038/7933 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 183VH UT WOS:000079574400027 PM 10207887 ER PT J AU Lee, JT Davidow, LS Warshawsky, D AF Lee, JT Davidow, LS Warshawsky, D TI Tsix, a gene antisense to Xist at the X-inactivation centre SO NATURE GENETICS LA English DT Article ID CHROMOSOME INACTIVATION; RNA; DNA; DIFFERENTIATION; STABILIZATION; INTERPHASE; EXPRESSION; NUCLEUS; INVITRO; REGION AB In mammals, dosage compensation is achieved by X inactivation(1) and is regulated in cis by the X-inactivation centre(2) (Xic) and Xist (refs 3-5). The Xic controls X-chromosome counting, choice of X to inactivate and initiation of silencing. Xic action culminates in a change in Xist RNA property from a scarce, unstable RNA (refs 6,7) to highly expressed Xist RNA that coats the future inactive X (ref. 8). Deleting a 65-kb region downstream of Xist results in constitutive Xist expression and X inactivation, implying the presence of a cis-regulatory element(9). In this region, we now report the discovery of a gene antisense to Xist. Tsix is a 40-kb RNA originating 15 kb downstream of Xist and transcribed across the Xist locus. Tsix sequence is conserved at the human XIC. Tsix RNA has no conserved ORFs, is seen exclusively in the nucleus and is localized at Xic. Before the onset of X inactivation, Tsix is expressed from both X chromosomes. At the onset of X inactivation, Tsix expression becomes monoallelic, is associated with the future active X and persists until Xist is turned off. Tsix is not found on the inactive X once cells enter the X-inactivation pathway. Tsix has features suggesting a role in regulating the early steps of X inactivation, but not the silencing step. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA. NR 26 TC 531 Z9 548 U1 2 U2 30 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1999 VL 21 IS 4 BP 400 EP 404 DI 10.1038/7734 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 181KC UT WOS:000079439700022 PM 10192391 ER PT J AU Schwartz, MW AF Schwartz, MW TI Mahogany adds color to the evolving story of body weight regulation SO NATURE MEDICINE LA English DT Editorial Material ID MELANOCORTIN RECEPTORS; FRAMESHIFT MUTATION; OBESITY; AGOUTI; MICE; MC4R C1 Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Harborview Med Ctr, VA Puget Sound Hlth Care Syst 151, Seattle, WA 98108 USA. RP Schwartz, MW (reprint author), Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, 1660 So Columbian Way, Seattle, WA 98108 USA. RI Schwartz, Michael/H-9950-2012 NR 12 TC 5 Z9 5 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1999 VL 5 IS 4 BP 374 EP 375 DI 10.1038/7365 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 183VG UT WOS:000079574300017 PM 10202918 ER PT J AU Frank, DA Mahajan, S Ritz, J AF Frank, DA Mahajan, S Ritz, J TI Fludarabine-induced immunosuppression is associated with inhibition of STAT1 signaling SO NATURE MEDICINE LA English DT Article ID TARGETED DISRUPTION; GENE; PROTEINS; CELLS; ACTIVATION; PHOSPHATE; LEUKEMIA; PATHWAY; GAMMA; ALPHA AB Fludarabine is a nucleoside analog used in the treatment of hematologic malignancies(1) that can induce severe and prolonged immunosuppression(2,3). Although it can be incorporated into the DNA of dividing cells, fludarabine is also a potent inhibitor of cells with a low growth fraction(4,5), thus it must have other mechanisms of action. STAT1, which is activated in response to many lymphocyte-activating cytokines including the interferons, is essential for cell-mediated immunity, as the absence of this protein is associated with prominent defects in the ability to control viral infections(6,7). Here we show that fludarabine, but not the immunosuppressant cyclosporine A, inhibits the cytokine-induced activation of STAT1 and STAT1-dependent gene transcription in normal resting or activated lymphocytes. Fludarabine caused a specific depletion of STAT1 protein (and mRNA) but not of other STATs. This loss of STAT1 was also seen in cells from patients treated with fludarabine in vivo. Brief exposure to fludarabine led to a sustained loss of STAT1, analogous to the prolonged period of immunosuppression induced by exposure to the drug in vivo. Thus, STAT1 may be a useful target in the development of new immunosuppressive and antineoplastic agents. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619, CA66996] NR 19 TC 136 Z9 145 U1 0 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1999 VL 5 IS 4 BP 444 EP 447 DI 10.1038/7445 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 183VG UT WOS:000079574300037 PM 10202937 ER PT J AU Wilson, DS Desplan, C AF Wilson, DS Desplan, C TI Structural basis of Hox specificity SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID COOPERATIVE DNA-BINDING; CRYSTAL-STRUCTURE; ENGRAILED HOMEODOMAIN; PBX PROTEINS; EXTRADENTICLE; COMPLEX; DROSOPHILA; DOMAIN; TRANSLOCATION; HETERODIMER AB On their own, the homeotic selector (Hox) transcriptional regulators bind very short, rather similar DNA sequences. To elevate their functional specificity, Hox proteins heterodimerize with other homeodomain-containing proteins. The structural basis for this fruitful partnership is now coming into view. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Rockefeller Univ, New York, NY 10021 USA. RP Wilson, DS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 35 TC 24 Z9 26 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD APR PY 1999 VL 6 IS 4 BP 297 EP 300 DI 10.1038/7524 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 182MT UT WOS:000079503300003 PM 10201389 ER PT J AU Lees, MB AF Lees, MB TI Hugo and Ann: A perfect partnership SO NEUROCHEMICAL RESEARCH LA English DT Biographical-Item ID ADRENOLEUKODYSTROPHY C1 EK Shriver Ctr, Div Biomed Sci, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lees, MB (reprint author), EK Shriver Ctr, Div Biomed Sci, 200 Trapelo Rd, Waltham, MA 02452 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD APR PY 1999 VL 24 IS 4 BP 465 EP 469 DI 10.1023/A:1022519426375 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 186XP UT WOS:000079756400002 ER PT J AU Caviness, VS Takahashi, T Nowakowski, RS AF Caviness, VS Takahashi, T Nowakowski, RS TI The G1 restriction point as critical regulator of neocortical neuronogenesis SO NEUROCHEMICAL RESEARCH LA English DT Article DE neuronogenesis; G1 restriction; cell cycle ID CORTICAL PROGENITOR CELLS; FIBROBLAST GROWTH-FACTOR; MURINE CEREBRAL WALL; CYCLIN-E; PROLIFERATIVE EPITHELIUM; DEVELOPMENTAL CONTROL; VENTRICULAR ZONE; DEPENDENT KINASE; GENE-EXPRESSION; MAMMALIAN-CELLS AB Neuronogenesis in the pseudostratified ventricular epithelium is the initial process in a succession of histogenetic events which give rise to the laminate neocortex. Here we review experimental findings in mouse which support the thesis that the restriction point of the G1 phase of the cell cycle is the critical point of regulation of the overall neuronogenetic process. The neuronogenetic interval in mouse spans 6 days. In the course of these 6 days the founder population and its progeny execute 11 cell cycles. With each successive cycle there is an increase in the fraction of postmitotic cells which leaves the cycle (the Q fraction) and also an increase in the length of the cell cycle due to an increase in the length of the G1 phase of the cycle. Q corresponds to the probability that postmitotic cells will exit the cycle at the restriction point of the G1 phase of the cell cycle. Q increases non-linearly, but the rate of change of Q with cycle (i.e., the first derivative) over the course of the neuronogenetic interval is a constant, k, which appears to be set principally by cell internal mechanisms which are species specific. Q also seems to be modulated, but at low amplitude, by a balance of mitogenic and antimitogenic influences acting from without the cell. We suggest that intracellular signal transduction systems control a general advance of Q during development and thereby determine the general developmental plan (i.e., cell number and laminar composition) of the neocortex and that external mitogens and anti-mitogens modulate this advance regionally and temporally and thereby produce regional modifications of the general plan. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Keio Univ, Sch Med, Dept Pediat, Tokyo 160, Japan. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. RP Caviness, VS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, 25 Fruit St, Boston, MA 02114 USA. RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NINDS NIH HHS [NS12005, NS33433] NR 67 TC 28 Z9 28 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD APR PY 1999 VL 24 IS 4 BP 497 EP 506 DI 10.1023/A:1022579712262 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 186XP UT WOS:000079756400007 PM 10227682 ER PT J AU Jacoby, LB MacCollin, M Parry, DM Kluwe, L Lynch, J Jones, D Gusella, JF AF Jacoby, LB MacCollin, M Parry, DM Kluwe, L Lynch, J Jones, D Gusella, JF TI Allelic expression of the NF2 gene in neurofibromatosis 2 and schwannomatosis SO NEUROGENETICS LA English DT Article DE neurofibromatosis 2; schwannomatosis; allelic expression; polymorphism ID GERM-LINE MUTATIONS; TUMOR-SUPPRESSOR GENE; SPORADIC MENINGIOMAS; TYPE-2 GENE; MERLIN; EPENDYMOMAS; PROTEIN; DISEASE; SEVERITY; FAMILY AB Neurofibromatosis type 2 (NF2) is a genetic disorder characterized by formation of multiple schwannomas and meningiomas due to inactivating mutations in the NF2 tumor suppressor gene on chromosome 22, We describe a polymorphism in the 3' untranslated region of the NF2 gene that is informative in about one-third of individuals, This polymorphism permitted an assessment of the relative expression of NF2 transcripts in lymphoblastoid cell RNA from 22 unrelated NF2 patients heterozygous for a germline NF2 mutation, along with 6 schwannomatosis patients, and 14 unaffected controls, Unequal allelic expression (1,8- to 20-fold) was detected in 15 of the NF2 cases, but in none of the schwannomatosis or control individuals, Underexpression of the NF2 mutant allele was documented for all 6 nonsense or frameshift mutations, 3 of 6 splice mutations, and 1 of 4 missense mutations, which, unexpectedly, was shown to alter the NF2 transcript and create a premature stop codon, In contrast, equal expression or slight overexpression of NF2 mutant alleles was observed for 2 in-frame deletions, 2 splice alterations, and 3 missense mutations, In the remaining 5 cases, the allele representing the mutant transcript was not known. Thus, truncating NF2 mutations, which are the most frequent alterations in NF2 patients and NF2-associated tumors, were associated with underexpression of the mutant allele, whereas the less common inframe alterations usually showed normal or slight overexpression of the mutant transcript. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Serv Neurol, Charlestown, MA 02129 USA. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Univ Hamburg, Hosp Eppendorf, D-20246 Hamburg, Germany. RP Jacoby, LB (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA51410]; NINDS NIH HHS [NS24279] NR 38 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD APR PY 1999 VL 2 IS 2 BP 101 EP 108 DI 10.1007/s100480050060 PG 8 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 200GD UT WOS:000080530500005 PM 10369886 ER PT J AU Eggenberger, M Born, W Zimmermann, U Lerner, EA Fischer, JA Muff, R AF Eggenberger, M Born, W Zimmermann, U Lerner, EA Fischer, JA Muff, R TI Maxadilan interacts with receptors for pituitary adenylyl cyclase activating peptide in human SH-SY5Y and SK-N-MC neuroblastoma cells SO NEUROPEPTIDES LA English DT Article ID POTENT VASODILATORY PEPTIDE; FLY LUTZOMYIA-LONGIPALPIS; FUNCTIONAL EXPRESSION; SALIVARY-GLANDS; POLYPEPTIDE; PACAP; CLONING AB Receptors for pituitary adenylyl cyclase activating peptide (PACAP) have been identified in human SH-SY5Y neuroblastoma cells with PACAP being 1000-fold more potent than vasoactive intestinal peptide (VIP) in [(125)I]PACAP binding inhibition and stimulation of cAMP accumulation. Maxadilan, a vasodilator peptide from the salivary gland of the sand fly Lutzomyia longipalpis also specifically bound to SH-SY5Y cells, and was equipotent to PACAP in [(125)I]PACAP and [(125)I]maxadilan binding inhibition, and stimulation of cAMP accumulation. Maxadilan and PACAP also increased the cytosolic free calcium concentration. in human SK-N-MC neuroblastoma cells PACAP, VIP and maxadilan equipotently stimulated cAMP accumulation. The maximal effects of VIP and maxadilan were additive and reached those of PACAP alone. In human T47D breast carcinoma cells PACAP and VIP were also equipotent in the stimulation of cAMP accumulation, but maxadilan was inactive. The results are consistent with the interaction of maxadilan with PACAP specific PAC(1) receptors in SH-SY5Y cells, but not with VPAC receptors, not differentiating between VIP and PACAP in T47D cells. Moreover, maxadilan is a PAC(1) receptor specific agonist which allows discrimination of co-expressed PAC(1) and VPAC receptors in SK-N-MC cells. C1 Univ Zurich, Dept Orthoped Surg, Res Lab Calcium Metab, Zurich, Switzerland. Univ Zurich, Dept Med, Res Lab Calcium Metab, Zurich, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Charlestown, MA USA. RP Muff, R (reprint author), Forchstr 340, CH-8008 Zurich, Switzerland. EM ramuz@balgrist.unizh.ch RI Muff, Roman/A-4247-2009 NR 27 TC 11 Z9 11 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 1999 VL 33 IS 2 BP 107 EP 114 DI 10.1054/npep.1999.0004 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 202PJ UT WOS:000080661100002 PM 10657479 ER PT J AU Cherrier, MM Mendez, MF Dave, M Perryman, KM AF Cherrier, MM Mendez, MF Dave, M Perryman, KM TI Performance on the Rey-Osterrieth Complex Figure test in Alzheimer disease and vascular dementia SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID IMPAIRMENT; AGE; RELIABILITY; CRITERIA; DEFICITS; MEMORY AB Background: Alzheimer disease (AD) and vascular dementia (VaD) are the two most common age-associated dementias. Neuropsychologic studies have demonstrated visuoconstructional impairment in AD and in VaD. Objective: This study used the Rey-Osterrieth Complex Figure to assess and compare specific aspects of visuoconstructional deficits in patients with AD, patients with VaD, and normal age-matched subjects. Method: Thirteen normal controls, 20 patients with AD, and 20 patients with VaD were given a neuropsychologic battery as part of a comprehensive evaluation for dementia. The groups were similar in age and education, and the VaD and AD groups had comparable levels of dementia. Based on their previous research on visual deficits in AD, the authors devised a new scoring system that divided the Rey-Osterrieth Complex Figure into six perceptual categories: right, left, upper, lower, basic gestalt, and inner detail. Results: Patients with AD and patients with VaD had significant deficits in all six Rey-Osterrieth Complex Figure scoring categories compared with normal controls. Patients with AD exhibited a pattern of deficits similar to that of patients with VaD, with one significant exception: The patients with AD had increased left-sided errors or inattention. Conclusions: These results suggest that left hemispatial inattention contributes to impaired performance on visuoconstructional tasks in AD. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Neurobehav Unit, Los Angeles, CA USA. RP Cherrier, MM (reprint author), VAPSHCS, GRECC182B, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 49 TC 20 Z9 22 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD APR PY 1999 VL 12 IS 2 BP 95 EP 101 PG 7 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 184WZ UT WOS:000079637900004 PM 10223256 ER PT J AU Marder, SR Rea, MM AF Marder, SR Rea, MM TI Michael J. Goldstein, 1930-1997 - In memoriam SO NEUROPSYCHOPHARMACOLOGY LA English DT Biographical-Item C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RP Marder, SR (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 1999 VL 20 IS 4 BP 399 EP 400 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 174TA UT WOS:000079050000013 ER PT J AU Kim, M Velier, J Chase, K Laforet, G Kalchman, MA Hayden, MR Won, L Heller, A Aronin, N Difiglia, M AF Kim, M Velier, J Chase, K Laforet, G Kalchman, MA Hayden, MR Won, L Heller, A Aronin, N Difiglia, M TI Forskolin and dopamine D-1 receptor activation increase huntingtin's association with endosomes in immortalized neuronal cells of striatal origin SO NEUROSCIENCE LA English DT Article DE huntingtin-interacting protein 1; dopamine receptors; Huntington's disease ID SACCHAROMYCES-CEREVISIAE; PLASMA-MEMBRANE; GROWTH-FACTOR; SUBSTANCE-P; BRAIN; CLATHRIN; INTERNALIZATION; ENDOCYTOSIS; EXPRESSION; INTERACTS AB Huntingtin is a cytoplasmic protein of unknown function that associates with vesicle membranes and microtubules. Its protein interactions suggest that huntingtin has a role in endocytosis and organelle transport. In this study we sought to identify factors that regulate the transport of huntingtin in striatal neurons, which are the cells most affected in Huntington's disease. In clonal striatal cells derived from fusions of neuroblastoma and embryonic striatal neurons, huntingtin localization is diffuse and slightly punctate in the cytoplasm. When these neurons were differentiated by treatment with forskolin, huntingtin redistributed to perinuclear regions, discrete puncta along plasma membranes, and branch points and terminal growth cones in neurites. Huntingtin staining overlapped with clathrin, a coat protein involved in endocytosis. Immunoblot analysis of subcellular membrane fractions separated by differential centrifugation confirmed that huntingtin immunoreactivity in differentiated neurons markedly increased in membrane fractions enriched with clathrin and with huntingtin-interacting protein 1. Dopamine treatment altered the subcellular localization of huntingtin and increased its expression in clathrin-enriched membrane fractions. The dopamine-induced changes were blocked by the D-1 antagonist SCH 23390 and were absent in a clonal cell line lacking D-1 receptors. Results suggest that the transport of huntingtin and its co-expression in clathrin and huntingtin-interacting protein 1-enriched membranes is influenced by activation of adenylyl cyclase and stimulation of dopamine D-1 receptors. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ British Columbia, Dept Med Genet, Vancouver, BC V6T 1Z4, Canada. Univ Chicago, Dept Pharmacol & Physiol Sci, Chicago, IL 60637 USA. Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA 01655 USA. RP Difiglia, M (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RI Kim, Manho/J-2738-2012; Hayden, Michael/D-8581-2011 OI Hayden, Michael/0000-0001-5159-1419 FU NIMH NIH HHS [MH 28942]; NINDS NIH HHS [NS 16367, NS 31579] NR 39 TC 33 Z9 35 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR PY 1999 VL 89 IS 4 BP 1159 EP 1167 DI 10.1016/S0306-4522(98)00400-X PG 9 WC Neurosciences SC Neurosciences & Neurology GA 166YR UT WOS:000078606100016 PM 10362304 ER PT J AU Harsh, G Loeffler, JS Thornton, A Smith, A Bussiere, M Chapman, PH AF Harsh, G Loeffler, JS Thornton, A Smith, A Bussiere, M Chapman, PH TI Stereotactic proton radiosurgery SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article AB The technique of stereotactic proton radiosurgery is discussed in depth in this article. The physics of the proton beam in radiosurgery is explained, and the different factors of beam delivery are examined. These key factors (correspondence to shape, accuracy of delineation of volume, correspondence to volume, and accuracy of delivery vary) with each of the radiosurgical techniques, from Gamma Knife surgery to linear accelerator therapy. Clinical series in the use of proton radiosurgery are also presented, with an emphasis on efficacy and uses. C1 Massachusetts Gen Hosp, Proton Radiosurg Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, NE Proton Therapy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Chapman, PH (reprint author), Massachusetts Gen Hosp, Proton Radiosurg Grp, 55 Fruit St, Boston, MA 02114 USA. NR 5 TC 14 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD APR PY 1999 VL 10 IS 2 BP 243 EP + PG 15 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 191XB UT WOS:000080046000006 PM 10099090 ER PT J AU Alexander, E Loeffler, JS AF Alexander, E Loeffler, JS TI The role of radiosurgery for glial neoplasms SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID MALIGNANT GLIOMA PATIENTS; STEREOTAXIC RADIOSURGERY; GLIOBLASTOMA-MULTIFORME; RADIATION-THERAPY; MAGNETIC-RESONANCE; LINEAR-ACCELERATOR; INITIAL MANAGEMENT; COMPUTERIZED-TOMOGRAPHY; BRAIN-TUMORS; SPECT IMAGES AB Malignant gliomas are one of the most serious challenges in clinical neurosurgery. Despite advances in surgical and radiation techniques, chemotherapy, and other systemic antineoplastic regimens, such as gene therapy and immunotherapy, patients who suffer from malignant gliomas often succumb to their disease. Although some success has been made with forms of enhanced surgical guidance and localized radiotherapy, current techniques are unable to eradicate the infiltrative glioma cells. C1 Brigham & Womens Hosp, Stereotact Radiosurg & Radiotherapy Ctr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Alexander, E (reprint author), Brigham & Womens Hosp, Stereotact Radiosurg & Radiotherapy Ctr, 75 Francis St,PBB3, Boston, MA 02115 USA. NR 66 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD APR PY 1999 VL 10 IS 2 BP 351 EP + PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 191XB UT WOS:000080046000015 PM 10099099 ER PT J AU Riley, LE Greene, MF AF Riley, LE Greene, MF TI Elective cesarean delivery to reduce the transmission of HIV SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ZIDOVUDINE TREATMENT; RISK C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Riley, LE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 11 Z9 11 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 1 PY 1999 VL 340 IS 13 BP 1032 EP 1033 DI 10.1056/NEJM199904013401308 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 182GA UT WOS:000079489800008 PM 10099146 ER PT J AU Ecker, JL Frigoletto, FD AF Ecker, JL Frigoletto, FD TI Routine ultrasound screening in low-risk pregnancies: Imperatives for further study SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID RANDOMIZED TRIAL; MANAGEMENT; IMPACT AB The benefits of screening ultrasonography in low-risk pregnancies are uncertain and require further investigation. As researchers organize future trials, however, they will need to define clearly the structure and content of the screening ultrasound examination and explicitly detail those outcomes considered important. Such studies must examine the effectiveness of screening sonography in comparison with and in the context of other available prenatal tests and screens. Until studies showing efficacy are available, screening ultrasound in low-risk pregnancies should be considered only when patients, guided by clinicians, consider the potential benefits to be of value. (Obstet Gynecol 1999;93:607-10. (C) 1999 by The American College of Obstetricians and Gynecologists.). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Mem Obstet Serv, Boston, MA 02114 USA. RP Frigoletto, FD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Mem Obstet Serv, Founders 4,33 Fruit St, Boston, MA 02114 USA. EM ffrigoletto@partners.org NR 12 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 1999 VL 93 IS 4 BP 607 EP 610 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 179ER UT WOS:000079313100027 PM 10214843 ER PT J AU Demetri, GD AF Demetri, GD TI Role of iron in optimizing responses of anemic cancer patients to erythropoietin - The Glaspy/Cavill article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID COMMUNITY ONCOLOGY; CHEMOTHERAPY; DISEASE; THERAPY C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Demetri, GD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 1999 VL 13 IS 4 BP 484 EP + PG 2 WC Oncology SC Oncology GA 368QB UT WOS:000090128000007 ER PT J AU Akpek, EK Uy, HS Christen, W Gurdal, C Foster, CS AF Akpek, EK Uy, HS Christen, W Gurdal, C Foster, CS TI Severity of episcleritis and systemic disease association SO OPHTHALMOLOGY LA English DT Article ID SCLERITIS AB Objective: To analyze patient characteristics and correlate between the site and severity of the inflammation and ocular and/or systemic disease association in a cohort of patients with episcleritis. Design: Retrospective case series. Methods: Medical records of 100 patients with episcleritis were reviewed. Data were analyzed using a customized database software. Results: The age range at presentation was 18 to 76 years (mean, 43; median, 44). Sixty-nine percent of the patients were female, Thirty-two (32%) patients had bilateral involvement. The episcleritis was nodular in 23 eyes (16%). Half of the patients had a concurrent eye disease. Associated systemic disease was found in 36 patients (36%), In two patients, episcleritis preceded a systemic vasculitic disease (Wegener granulomatosis and Cogan syndrome). Ocular complications included uveitis (11.4%), corneal involvement (15%), and glaucoma (7.8%), No significant correlation of the site and severity of inflammation to the presence of associated systemic or ocular diseases was found, The mean follow-up was 16.5 months. Twenty-eight patients experienced recurrence of episcleritis during the follow-up. Half of the patients required treatment with oral nonsteroidal anti-inflammatory drugs. Conclusions: Episcleritis is usually a benign, self-limited disease, but it should not be trivialized since it may be associated with systemic disease and ocular complications. A careful review of systems should be performed in all patients presenting with episcleritis, and this should be repeated at least annually during the follow-up, A thorough eye examination is obviously essential to detect and treat ocular complications. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ocular Immunol Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Cornea & External Dis Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ocular Immunol Serv, 243 Charles St, Boston, MA 02114 USA. NR 9 TC 27 Z9 28 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1999 VL 106 IS 4 BP 729 EP 731 DI 10.1016/S0161-6420(99)90157-4 PG 3 WC Ophthalmology SC Ophthalmology GA 180XB UT WOS:000079410200026 PM 10201593 ER PT J AU Akpek, EK Polcharoen, W Ferry, JA Foster, CS AF Akpek, EK Polcharoen, W Ferry, JA Foster, CS TI Conjunctival lymphoma masquerading as chronic conjunctivitis SO OPHTHALMOLOGY LA English DT Article ID TISSUE LYMPHOMA; CLASSIFICATION; NEOPLASMS; LESIONS AB Objective: Malignant lesions of the conjunctiva may present with slowly evolving signs resembling inflammation. The authors describe the clinical and histopathologic findings of two patients with bilateral conjunctival lymphoma who presented with a history of chronic conjunctivitis without clinically noticeable subconjunctival nodules, Design: Case report, Participants: Two patients. Intervention: Both patients underwent conjunctival biopsy for evaluation of persistent conjunctival inflammation that did not respond to various medical treatment methods. Results: Histopathologic examination revealed extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue type) in one patient and follicle center lymphoma in the other patient. Both patients subsequently received radiation therapy and achieved a complete remission with no evidence of recurrence in the follow-up period of 20 and 16 months, respectively. Conclusions: Conjunctival lymphoma should be included in the differential diagnoses of chronic conjunctivitis, Persisting signs and symptoms of conjunctivitis not responding to standard treatment should prompt biopsy. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Serv Immunol, 243 Charles St, Boston, MA 02114 USA. NR 17 TC 25 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1999 VL 106 IS 4 BP 757 EP 760 DI 10.1016/S0161-6420(99)90163-X PG 4 WC Ophthalmology SC Ophthalmology GA 180XB UT WOS:000079410200032 PM 10201599 ER PT J AU Rivkin, A Meara, JG Li, KK Potter, C Wenokur, R AF Rivkin, A Meara, JG Li, KK Potter, C Wenokur, R TI Squamous cell metastasis from the tongue to the myocardium presenting as pericardial effusion SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID HEART C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. RP Meara, JG (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 9 Z9 9 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 1999 VL 120 IS 4 BP 593 EP 595 DI 10.1053/hn.1999.v120.a84489 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 184DF UT WOS:000079594100039 PM 10187969 ER PT J AU Williams, MA Havel, PJ Schwartz, MW Leisenring, WM King, IB Zingheim, RW Zebelman, AJ Luthy, DA AF Williams, MA Havel, PJ Schwartz, MW Leisenring, WM King, IB Zingheim, RW Zebelman, AJ Luthy, DA TI Pre-eclampsia disrupts the normal relationship between serum leptin concentrations and adiposity in pregnant women SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID INDUCED HYPERTENSION; PLASMA LEPTIN; LIPID-PEROXIDATION; AMNIOTIC-FLUID; PREECLAMPSIA; PLACENTA; INSULIN; WEIGHT; HUMANS; RISK AB The adipocyte hormone, leptin, is secreted in proportion to adipose mass and is implicated in the regulation of energy balance via its central actions on food intake and sympathetic nervous system activity. The placenta was also shown recently to be a possible source of leptin in pregnant women, raising the possibility that the normal relationship between leptin and adiposity may be altered in pre-eclampsia. We therefore sought to assess the extent to which maternal second trimester serum leptin concentrations differed for women who would subsequently develop pre-eclampsia and those who would remain normotensive. This nested case-control study population comprised 38 women with pregnancy-induced hypertension and proteinuria (pre-eclampsia) and 192 normotensive women. Multiple least-squares regression procedures were used to assess the independent relationship between leptin concentrations and risk of pre-eclampsia. Serum leptin concentrations, measured by radioimmunoassay, were highly correlated with maternal pre-pregnancy and second trimester body mass index (r = 0.71 and r = 0.74 respectively; P < 0.001 for both) among normotensive women, and to a lesser extent among women who developed pre-eclampsia (r = 0.29 and r = 0.42; P = 0.09 and 0.02 respectively). Among women with a pre-pregnancy body mass index of less than or equal to 25 kg/m(2), pre-eclampsia cases compared with controls had higher mean second trimester leptin concentrations after adjustment for confounding factors. In contrast, preeclampsia cases had lower mean leptin concentrations than controls for those women with a pre-pregnancy body mass index above 25 kg/m(2). Other factors in addition to the level of adiposity may therefore influence serum leptin concentrations in pre-eclamptic pregnant women. Our results suggest the possibility that leptin, like several other placentally derived substances (e.g. steroid hormones, eicosanoids and cytokines), may be involved in the pathogenesis of pre-eclampsia. Further work is needed to confirm our findings and to assess the metabolic importance and determinants of leptin concentrations in uncomplicated and preeclamptic pregnancies. C1 Swedish Med Ctr, Ctr Perinatal Studies 449N, Seattle, WA 98122 USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Program Biostat, Seattle, WA 98104 USA. Dynacare Lab Pathol, Seattle, WA USA. RP Williams, MA (reprint author), Swedish Med Ctr, Ctr Perinatal Studies 449N, 747 Broadway, Seattle, WA 98122 USA. RI Schwartz, Michael/H-9950-2012 FU NICHD NIH HHS [HD/HL-32562]; NIDDK NIH HHS [DK-35747, DK-50129] NR 31 TC 27 Z9 28 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD APR PY 1999 VL 13 IS 2 BP 190 EP 204 PG 15 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 187DV UT WOS:000079772400007 PM 10214609 ER PT J AU Frazer, BA Fried, B Fujino, T Sleckman, BP AF Frazer, BA Fried, B Fujino, T Sleckman, BP TI Host-parasite relationships between Echinostoma caproni and RAG-2-deficient mice SO PARASITOLOGY RESEARCH LA English DT Article ID INTESTINAL TREMATODE; C3H/HEN MICE; ICR MOUSE; NMRI MICE; EXPULSION; TRIVOLVIS; HYPERPLASIA; INFECTIVITY; RETENTION AB The RAG-2-deficient mouse, a strain of genetically altered mice lacking B- and T-lymphocytes, was used as a host for Echinostoma caproni. In all, 12 male RAG mice were exposed to 25 cysts each, and 12 served as uninfected controls. Mice were necropsied at 2 and 3 weeks postinfection (p.i.). The mean number ISE (9.7 +/- 2.4) of worms recovered from infected mice at 2 weeks p.i, was not significantly different from that recovered at 3 weeks p.i. (6.5 +/- 2.2). The intestinal circumference of infected RAG mice was significantly greater than that of the controls at 2 and 3 weeks p.i. A significant goblet cell hyperplasia occurred at 2 weeks p.i., but the response was not effective in eliminating worms from the RAG mice. The effect of a high cyst burden was examined by exposure of 8 RAG and 8 ICR mice to 100 cysts each. The body length and area and the oral sucker area of worms grown in RAG mice were significantly greater than those of worms grown in ICR mice. Worm recovery at up to 3 months p.i. was examined in RAG mice exposed to 25 cysts and necropsied every 2 weeks p.i. The mean worm recovery recorded at 2 weeks p.i. was significantly greater than that noted at 12 weeks p.i., at which time worm rejection from the RAG mouse host first occurred. The RAG mouse is a useful host for studies on E. caproni in a murine host that lacks B- and T-lymphocytes. C1 Lafayette Coll, Dept Biol, Easton, PA 18042 USA. Yamagata Univ, Fac Sci, Dept Biol, Yamagata 9908560, Japan. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Fried, B (reprint author), Lafayette Coll, Dept Biol, Easton, PA 18042 USA. NR 18 TC 5 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0044-3255 J9 PARASITOL RES JI Parasitol. Res. PD APR PY 1999 VL 85 IS 4 BP 337 EP 342 DI 10.1007/s004360050558 PG 6 WC Parasitology SC Parasitology GA 170UY UT WOS:000078826500016 PM 10099018 ER PT J AU Sehnert, AJ Fishman, MC Stainier, DYR AF Sehnert, AJ Fishman, MC Stainier, DYR TI Molecular-genetic analysis of the silent heart mutation in zebrafish SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 356 BP 62A EP 62A DI 10.1203/00006450-199904020-00373 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476700357 ER PT J AU Bode, HH Boepple, PA Crawford, JD Grant, DB Preece, MA AF Bode, HH Boepple, PA Crawford, JD Grant, DB Preece, MA TI Growth and final height of patients with mixed gonadal dysgenesis (MGD) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Sydney Childrens Hosp, Sydney, NSW, Australia. Australian Paediat Grp, Sydney, NSW, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Great Ormond St Hosp Children, London WC1N 3JH, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 490 BP 85A EP 85A DI 10.1203/00006450-199904020-00507 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476700491 ER PT J AU Belkind-Gerson, J Choi, RS Kaplan, LM AF Belkind-Gerson, J Choi, RS Kaplan, LM TI Intestinal epithelial cells direct their own innervation in a co-culture system SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Hosp Nino Moerlense, Cuernavaca, Morelos, Mexico. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 631 BP 109A EP 109A DI 10.1203/00006450-199904020-00648 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476700632 ER PT J AU Newburg, DS McCormick, B Chaturvedi, P Siber, AM Warren, CD AF Newburg, DS McCormick, B Chaturvedi, P Siber, AM Warren, CD TI Inhibition of Salmonella typhimurium by human milk sulfatides SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Shriver Ctr, Waltham, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 671 BP 116A EP 116A DI 10.1203/00006450-199904020-00688 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476700672 ER PT J AU Grabowski, EF Carter, C Tsukurov, O Conroy, N Hsu, CY Abbott, WM Ingelfinger, JR Orkin, RW AF Grabowski, EF Carter, C Tsukurov, O Conroy, N Hsu, CY Abbott, WM Ingelfinger, JR Orkin, RW TI A comparison of human umbilical vein and adult saphenous vein endothelial cells under static and flow conditions SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 853 BP 146A EP 146A DI 10.1203/00006450-199904020-00870 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476700854 ER PT J AU Baba, TW Liska, V Hoffman-Lehmann, R Vlasak, J Posner, MR Cavacini, LA Katinger, H Bernacky, BJ Rizvi, TA Keeling, M Schmidt, R Ruprecht, RM AF Baba, TW Liska, V Hoffman-Lehmann, R Vlasak, J Posner, MR Cavacini, LA Katinger, H Bernacky, BJ Rizvi, TA Keeling, M Schmidt, R Ruprecht, RM TI Human monoclonal antibodies protect neonatal and adult rhesus monkeys from mucosal or parenteral immunodeficiency virus exposure SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Inst Appl Microbiol, Vienna, Austria. Univ Texas, MD Anderson Cancer Ctr, Bastrop, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 907 BP 156A EP 156A DI 10.1203/00006450-199904020-00924 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476700908 ER PT J AU Stack, AM Malley, R Thompson, CM Saladino, RA AF Stack, AM Malley, R Thompson, CM Saladino, RA TI A novel murine model of primary respiratory syncytial virus (RSV) infection SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Infect Dis Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 1023 BP 175A EP 175A DI 10.1203/00006450-199904020-01040 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476701024 ER PT J AU Dai, DW Nanthkumar, NN Newburg, DS Walker, WA AF Dai, DW Nanthkumar, NN Newburg, DS Walker, WA TI Region-specific regulation and cortisone induction of glycosyltransferases expression in the developing intestine SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Shriver Ctr Mental Retardat, Glycobiol Lab, Waltham, MA 02254 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 1124 BP 192A EP 192A DI 10.1203/00006450-199904020-01141 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476701125 ER PT J AU Biswas, S Marlborough, C Johnson, L Golombek, SG LaGamma, EF AF Biswas, S Marlborough, C Johnson, L Golombek, SG LaGamma, EF TI The use of bedside pulmonary mechanics with synchronized, assist-control ventilation to achieve optimal FRC and lower mean airway pressures (MAP) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Stony Brook, Univ Hosp, Stony Brook, NY 11794 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 1741 BP 296A EP 296A DI 10.1203/00006450-199904020-01758 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476701742 ER PT J AU Sanchez, LS Fineman, JR Barry, AJ Black, SM AF Sanchez, LS Fineman, JR Barry, AJ Black, SM TI Phosphodiesterase 5 (PDE5) enzyme activity is increased in lambs with increased pulmonary blood flow and pulmonary hypertension SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anaesthesia, Charlestown, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Cardiothorac Surg, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 1878 BP 318A EP 318A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476701878 ER PT J AU Sanchez, LS Russell, JA Steinhorn, RH AF Sanchez, LS Russell, JA Steinhorn, RH TI Phosphodiesterase 5 (PDE5) enzyme activity and gene expression are altered in newborn lambs with persistent pulmonary hypertension (PPHN) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anaesthesia, Charlestown, MA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. SUNY Buffalo, Dept Pediat, Buffalo, NY 14260 USA. SUNY Buffalo, Dept Physiol, Buffalo, NY 14260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 1879 BP 318A EP 318A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476701879 ER PT J AU Kuizon, BD Salusky, IB Juppner, H Willsey, P Goodman, WG AF Kuizon, BD Salusky, IB Juppner, H Willsey, P Goodman, WG TI An animal model to evaluate key regulators of endochondral bone growth in renal failure SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 1969 BP 334A EP 334A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476701969 ER PT J AU Kuizon, BD Goodman, WG Gales, B Juppner, H Salusky, IB AF Kuizon, BD Goodman, WG Gales, B Juppner, H Salusky, IB TI Skeletal effects of growth hormone and calcitriol in children with ESRD SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 1968 BP 334A EP 334A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476701968 ER PT J AU Tang, SS Diamant, DE Min, T Ingelfinger, JR AF Tang, SS Diamant, DE Min, T Ingelfinger, JR TI Promoter analysis of rat AT(2) receptor gene in immortalized rat proximal tubule cells (IRPTC) SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 MA 1991 BP 337A EP 337A DI 10.1203/00006450-199904020-02007 PN 2 PG 1 WC Pediatrics SC Pediatrics GA 182AQ UT WOS:000079476701991 ER PT J AU Hoal-van Helden, EG Epstein, J Victor, TC Hon, DN Lewis, LA Beyers, N Zurakowski, D Ezekowitz, RAB van Helden, PD AF Hoal-van Helden, EG Epstein, J Victor, TC Hon, DN Lewis, LA Beyers, N Zurakowski, D Ezekowitz, RAB van Helden, PD TI Mannose-binding protein B allele confers protection against tuberculous meningitis SO PEDIATRIC RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SERINE-PROTEASE; COMPLEMENT PATHWAY; GENE; ASSOCIATION; ACTIVATION; MUTATIONS; SYSTEM; LECTIN; PROGRESSION AB Inhalation is the principal mode of entry for Mycobacterium tuberculosis in humans. Primary infection is usually restricted to the lungs and contiguous lymph nodes. In a subset of infected individuals, predominantly children, the infection is spread hematogenously to the meninges. The host factors that influence the development of tuberculous meningitis have not been well elucidated. The mannose-binding protein (MBP), a serum protein, is considered as an "ante-antibody." MBP has been shown to bind mycobacteria and acts as an opsonin in vitro. Although MBP plays a role in first-line host defense, it may under certain circumstances be deleterious to the host. In tuberculosis (TB), MBP may assist the spread of this intracellular pathogen. Therefore, we hypothesized that MBP genotypes that result in a phenotype of low MBP levels might be protective. We studied a well-defined South African population in which TB has reached epidemic levels. We found that the MBP B allele (G54D), which disrupts the collagen region of the protein and results in low MBP levels, was found in 22 of 79 (28%) of the TB-negative controls from the same community, compared with 12 of 91 (13%) of the patients with pulmonary TB (p < 0.017), and 5 of 64 (8%) of patients with tuberculous meningitis (p < 0.002). In addition, we found significantly lower serum MBP concentrations in TB-negative controls compared with postacute phase, fully recovered TB patients (p < 0.004). These findings suggest that the MBP B allele affords protection against tuberculous meningitis. C1 Univ Stellenbosch, MRC, Ctr Mol & Cellular Biol, Dept Biochem Med, ZA-7505 Tygerberg, South Africa. Univ Stellenbosch, Sch Med, Dept Pediat, ZA-7505 Tygerberg, South Africa. Harvard Univ, Sch Med, Boston, MA 02114 USA. Childrens Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. RP Hoal-van Helden, EG (reprint author), Univ Stellenbosch, MRC, Ctr Mol & Cellular Biol, Dept Biochem Med, POB 19063, ZA-7505 Tygerberg, South Africa. OI Hoal, Eileen/0000-0002-6444-5688 FU NHLBI NIH HHS [HL43510] NR 50 TC 120 Z9 121 U1 0 U2 2 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1999 VL 45 IS 4 BP 459 EP 464 DI 10.1203/00006450-199904010-00002 PN 1 PG 6 WC Pediatrics SC Pediatrics GA 182AK UT WOS:000079476200002 PM 10203135 ER PT J AU Shannon, DC AF Shannon, DC TI Method of analyzing QT interval can't support conclusions SO PEDIATRICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Pediat Pulm Unit, Boston, MA 02114 USA. RP Shannon, DC (reprint author), Massachusetts Gen Hosp, Pediat Pulm Unit, VBKBA 015,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 1999 VL 103 IS 4 BP 819 EP 819 DI 10.1542/peds.103.4.819 PG 1 WC Pediatrics SC Pediatrics GA 182TZ UT WOS:000079515400041 PM 10103312 ER PT J AU Perrin, JM AF Perrin, JM TI Universality, inclusion, and continuity: Implications for pediatrics SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Ambulatory-Pediatrics-Association CY MAY 03-08, 1998 CL NEW ORLEANS, LOUISIANA SP Ambulatory Pediat Assoc ID SPECIAL NEEDS; PRIMARY-CARE; HEALTH; CHILDREN C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Pediat, Boston, MA 02114 USA. RP Perrin, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Pediat, WACC 715, Boston, MA 02114 USA. NR 21 TC 8 Z9 8 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 1999 VL 103 IS 4 SU S BP 859 EP 863 PG 5 WC Pediatrics SC Pediatrics GA 183YW UT WOS:000079583400004 PM 10103322 ER PT J AU Kemper, KJ Cassileth, B Ferris, T AF Kemper, KJ Cassileth, B Ferris, T TI Holistic pediatrics: A research agenda SO PEDIATRICS LA English DT Article DE holistic pediatrics; research ID ALTERNATIVE MEDICINE THERAPIES; PRIMARY-CARE; HEALTH-CARE; UNCONVENTIONAL MEDICINE; COMPLEMENTARY MEDICINE; NATIONAL SURVEY; UNITED-STATES; PHYSICIANS; CHILDREN; PREVALENCE AB Increasing numbers of American families seek complementary and alternative medical care (CAM) for their children; at the same time health care organization and financing are undergoing radical changes, The combination of these factors provides a powerful incentive fur research on the effectiveness and safety of CAM therapies and their role in treating children. This article describes a rationale, spectrum, priorities, and methodologies for a research agenda in holistic pediatrics. The top priorities are clinical research projects addressing the safety and effectiveness of alternative therapies used for vulnerable children suffering from serious illnesses. Additionally, major research questions involve the impact of the various definitions such as "alternative," "complementary," "folk," "integrative," and "holistic" medicine on perceptions of health care, professional education, and funding of products and services. Research efforts in alternative therapies need to address explicitly the tremendous heterogeneity between and among the practices, beliefs, and providers of professional and lay services. Qualitative ethnographic research is needed to understand the consequences of diverse explanatory models and meanings of health and illness for patient-provider communication, adherence with professional recommendations, and satisfaction with care. Health services researchers need to address questions related to the epidemiology of CAM practices, health manpower issues, practice characteristics and the process and content of health care and how discoveries about CAM care may enhance the quality of mainstream health services. A rationale is provided for prioritizing certain conditions and therapies within these efforts. C1 Childrens Hosp, Ctr Holist Pediat Educ & Res, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Kemper, KJ (reprint author), Ctr Holist Pediat Educ & Res, 300 Longwood Ave, Boston, MA 02115 USA. NR 79 TC 43 Z9 43 U1 3 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 1999 VL 103 IS 4 SU S BP 902 EP 909 PG 8 WC Pediatrics SC Pediatrics GA 183YW UT WOS:000079583400011 PM 10103329 ER PT J AU Mulholland, SE Lee, S McAuliffe, DJ Doukas, AG AF Mulholland, SE Lee, S McAuliffe, DJ Doukas, AG TI Cell loading with laser-generated stress waves: The role of the stress gradient SO PHARMACEUTICAL RESEARCH LA English DT Article DE drug delivery; drug carriers; red blood cells; sonophoresis; shock waves; ultrasound; phonophoresis; phonoporation ID INDUCED SHOCK-WAVES; IN-VITRO; PLASMA-MEMBRANE; PERMEABILIZATION; TRANSFECTION; DELIVERY; INVITRO; TISSUE; DNA AB Purpose. To determine the dependence of the permeabilzation of the plasma membrane on the characteristics of laser-generated stress waves. Methods. Laser pulses can generate stress waves by ablation. Depending on the laser wavelength, fluence, and target material, stress waves of different characteristics (rise time, peak stress) can be generated. Human red blood cells were subjected to stress waves and the permeability changes were measured by uptake of extracellular dye molecules. Results. A fast rise time (high stress gradient) of the stress wave was required for the permeabilization of the plasma membrane. While the membrane was permeable, the cells could rapidly uptake molecules From the surrounding medium by diffusion. Conclusions. Stress waves provide a potentially powerful tool for drug delivery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Doukas, AG (reprint author), Inst Genet, 1 Burtt Rd, Andover, MA 01810 USA. NR 28 TC 49 Z9 50 U1 0 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD APR PY 1999 VL 16 IS 4 BP 514 EP 518 DI 10.1023/A:1018814911497 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 188HX UT WOS:000079841700007 PM 10227705 ER PT J AU Altshuler, GB Zenzie, HH Erofeev, AV Smirnov, MZ Anderson, RR Dierickx, C AF Altshuler, GB Zenzie, HH Erofeev, AV Smirnov, MZ Anderson, RR Dierickx, C TI Contact cooling of the skin SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PORT-WINE-STAIN; PULSED-LASER IRRADIATION; THERMOCHEMICAL DAMAGE; THERMAL RESPONSE; SURGERY AB Skin precooling can be used to reduce epidermal thermal damage in laser procedures (such as hair removal) where the target structures are located up to several millimetres below the skin surface. We have developed and experimentally verified a computational model that describes contact precooling of a multilayered skin structure prior to laser irradiation. The skin surface is assumed to be brought into thermal contact with a cold plate made of material with a high thermal conductivity. The approximate analytical solution for the skin temperature is obtained by considering the plate as a local heat sink. The time evolution of temperature (in both the skin and the plate) is simulated numerically to yield the optimal cooling parameters. To experimentally verify the numerical results of the model, we performed direct measurements of skin temperature for contact cooling with a sapphire plate held at several different temperatures in the range +10 to -30 degrees C. C1 Palomar Med Prod Inc, Lexington, MA 02173 USA. Inst Fine Mech, St Petersburg 197101, Russia. Opt Laser Ctr, St Petersburg 197101, Russia. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Altshuler, GB (reprint author), Palomar Med Prod Inc, 45 Hartwell Ave, Lexington, MA 02173 USA. NR 20 TC 70 Z9 73 U1 0 U2 7 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD APR PY 1999 VL 44 IS 4 BP 1003 EP 1023 DI 10.1088/0031-9155/44/4/014 PG 21 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 186UA UT WOS:000079746700016 PM 10232811 ER PT J AU Rodriguez, A Cao, YL Ibarra, C Pap, S Vacanti, M Eavey, RD Vacanti, CA AF Rodriguez, A Cao, YL Ibarra, C Pap, S Vacanti, M Eavey, RD Vacanti, CA TI Characteristics of cartilage engineered from human pediatric auricular cartilage SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT American-Society-of-Pediatric-Oncology Meeting CY MAY 15, 1997 CL SCOTTSDALE, ARIZONA SP Amer Soc Pediat Oncol ID CHONDROCYTES; TRANSPLANTATION; EXPRESSION; MOLECULES; MICROTIA; POLYMERS; GROWTH AB In the repair of cartilage defects, autologous tissue offers the advantage of lasting biocompatibility. The ability of bovine chondrocytes isolated from hyaline cartilage to generate tissue-engineered cartilage in a predetermined shape, such as a human ear, has been demonstrated; however, the potential of chondrocytes isolated from human elastic cartilage remains unknown. In this study, the authors examined the multiplication characteristics of human auricular chondrocytes and the ability of these cells to generate new elastic cartilage as a function of the length of time they are maintained in vitro. Human auricular cartilage, harvested from patients 5 to 17 years of age, was digested in collagenase, and the chondrocytes were isolated and cultured in vitro for up to 12 weeks. Cells were trypsinized, counted, and passaged every 2 weeks. Chondrocyte-polymer (polyglycolic acid) constructs were created at each passage and then implanted into athymic mice for 8 weeks. The ability of the cells to multiply in vitro and their ability to generate new cartilage as a function of the time they had been maintained in vitro were studied. A total of 31 experimental constructs from 12 patients were implanted and compared with a control group of constructs without chondrocytes. In parallel, a representative sample of cells was evaluated to determine the presence of collagen. The doubling rate of human auricular chondrocytes in vitro remained constant within the population studied. New tissue developed in 22 of 31 experimental implants. This tissue demonstrated the physical characteristics of auricular cartilage on gross inspection. Histogically, specimens exhibited dense cellularity and lacunae-containing cells embedded in a basophilic matrix. The specimens resembled immature cartilage and were partially devoid of the synthetic material of which the construct had been composed. Analyses for collagen, proteoglycans, and elastin were consistent with elastic cartilage. No cartilage was detected in the control implants. Human auricular chondrocytes multiply well in vitro and possess the ability to form new cartilage when seeded onto a three-dimensional scaffold. These growth characteristics might some day enable chondrocytes isolated from a small auricular biopsy to be expanded in vitro to generate a large, custom-shaped, autologous graft for clinical reconstruction of a cartilage defect, such as for congenital microtia. C1 Univ Massachusetts, Dept Anesthesia, Amherst, MA 01003 USA. Univ Massachusetts, Lab Tissue Engn, Amherst, MA 01003 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rodriguez, A (reprint author), 46 Shrewsbury Green Dr,Apt 1, Shrewsbury, MA 01545 USA. NR 20 TC 82 Z9 83 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR PY 1999 VL 103 IS 4 BP 1111 EP 1119 DI 10.1097/00006534-199904040-00001 PG 9 WC Surgery SC Surgery GA 175RC UT WOS:000079107900001 PM 10088494 ER PT J AU Premnath, V Bellare, A Merrill, EW Jasty, M Harris, WH AF Premnath, V Bellare, A Merrill, EW Jasty, M Harris, WH TI Molecular rearrangements in ultra high molecular weight polyethylene after irradiation and long-term storage in air SO POLYMER LA English DT Article DE ultra high molecular weight polyethylene (UHMWPE); radiation; aging ID INDUCED CRYSTALLINITY CHANGES; HIGH-DENSITY POLYETHYLENE; SMALL-ANGLE SCATTERING; LINEAR POLYETHYLENE; CROSS-LINKING; RADIATION; IMPLANTS; STERILIZATION; ORIENTATION; OXIDATION AB Molecular rearrangements and alterations in supermolecular structure of ultra high molecular weight polyethylene (UHMWPE) due to cross-linking and oxidation-induced chain scission following irradiation and subsequent storage in air at room temperature have been studied over a period of 29 months. The techniques that were used are: equilibrium swelling in decalin, differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), Fourier transform infrared spectroscopy (FTIR) and electron spin resonance (ESR). The experimental results indicate that immediately after irradiation, cross-linking and an increase in crystallinity are the important processes. With time, chain scission induced by oxidation takes place resulting in a new phase of thinner crystallites in the amorphous region. In the absence of oxygen diffusion limitations, the free radicals survive for 30 months in the form of peroxides. The effect produced by higher doses and shorter aging times correspond to those produced by lower doses and longer aging times, thus, suggesting a superposition law between dose and aging time. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Program Polymer Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Orthopaed Biomech Lab, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Merrill, EW (reprint author), MIT, Dept Chem Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. NR 61 TC 81 Z9 81 U1 3 U2 23 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0032-3861 J9 POLYMER JI Polymer PD APR PY 1999 VL 40 IS 9 BP 2215 EP 2229 DI 10.1016/S0032-3861(98)00438-8 PG 15 WC Polymer Science SC Polymer Science GA 160DQ UT WOS:000078215500005 ER PT J AU Yao, JK Leonard, S Reddy, R AF Yao, JK Leonard, S Reddy, R TI Phospholipid and polyunsaturated fatty acid defects in postmortem schizophrenic brain SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 1999 VL 36 IS 1-3 SI SI BP 77 EP 78 PG 2 WC Psychiatry SC Psychiatry GA 174XH UT WOS:000079061400215 ER PT J AU Allen, DN Anastasiou, A Goldstein, G Gurklis, JA Gilbertson, M van Kammen, DP AF Allen, DN Anastasiou, A Goldstein, G Gurklis, JA Gilbertson, M van Kammen, DP TI Effects of antipsychotics on relationships between frontal lobe functioning, psychomotor poverty, and disorganization syndromes in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 1999 VL 36 IS 1-3 SI SI BP 123 EP 124 PG 2 WC Psychiatry SC Psychiatry GA 174XH UT WOS:000079061400341 ER PT J AU Allen, DN Goldstein, G Aldarondo, F Wiemert, SR AF Allen, DN Goldstein, G Aldarondo, F Wiemert, SR TI Neurocognitive consequences of alcoholism in patients diagnosed with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Highland Dr Div 151R, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 1999 VL 36 IS 1-3 SI SI BP 123 EP 123 PG 1 WC Psychiatry SC Psychiatry GA 174XH UT WOS:000079061400340 ER PT J AU Wood, AE Secrest, L Tapp, A AF Wood, AE Secrest, L Tapp, A TI Negative symptoms, executive function, and level of functional impairment in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Amer Lake Div, Tacoma, WA 98493 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 1999 VL 36 IS 1-3 SI SI BP 157 EP 157 PG 1 WC Psychiatry SC Psychiatry GA 174XH UT WOS:000079061400447 ER PT J AU Kee, KS Brekke, JS Salveson, DF Green, MF AF Kee, KS Brekke, JS Salveson, DF Green, MF TI Associations between perception of emotion and types of psychosocial functioning in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 1999 VL 36 IS 1-3 SI SI BP 172 EP 172 PG 1 WC Psychiatry SC Psychiatry GA 174XH UT WOS:000079061400493 ER PT J AU Kern, RS Robertson, MJ Niv, N Zaidel, L Parsa, M Green, MF AF Kern, RS Robertson, MJ Niv, N Zaidel, L Parsa, M Green, MF TI Neurocognitive correlates of prosocial and deviant behavior in treatment-resistant schizophrenia inpatients SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 1999 VL 36 IS 1-3 SI SI BP 173 EP 173 PG 1 WC Psychiatry SC Psychiatry GA 174XH UT WOS:000079061400496 ER PT J AU Kuperberg, GR McGuire, PK David, AS AF Kuperberg, GR McGuire, PK David, AS TI Dissociations among pragmatic, semantic, syntactic processing schizophrenic thought-disorder SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI David, Anthony/C-1315-2011 OI David, Anthony/0000-0003-0967-774X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 1999 VL 36 IS 1-3 SI SI BP 175 EP 175 PG 1 WC Psychiatry SC Psychiatry GA 174XH UT WOS:000079061400503 ER PT J AU Marder, SR Wirshing, WC Glynn, S Wirshing, DA Mintz, J Liberman, RP AF Marder, SR Wirshing, WC Glynn, S Wirshing, DA Mintz, J Liberman, RP TI Risperidone and haloperidol in maintenance treatment: Interactions with psychosocial treatments SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 W Los Angeles VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 22, Los Angeles, CA 90073 USA. W Los Angeles VA Med Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. RI Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 1999 VL 36 IS 1-3 SI SI BP 288 EP 288 PG 1 WC Psychiatry SC Psychiatry GA 174XH UT WOS:000079061400835 ER PT J AU Glynn, SM Marder, SR Liberman, RP Blair, K Ross, D Mintz, J Wirshing, W Wirshing, DA AF Glynn, SM Marder, SR Liberman, RP Blair, K Ross, D Mintz, J Wirshing, W Wirshing, DA TI Community skills training increases benefits accruing from clinic-based behavioral psychiatric rehabilitation SO SCHIZOPHRENIA RESEARCH LA English DT Meeting Abstract C1 W Los Angeles VA Med Ctr B151J, Los Angeles, CA 90073 USA. RI Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR PY 1999 VL 36 IS 1-3 SI SI BP 325 EP 325 PG 1 WC Psychiatry SC Psychiatry GA 174XH UT WOS:000079061400936 ER PT J AU Langer, RS Vacanti, JP AF Langer, RS Vacanti, JP TI Tissue engineering: The challenges ahead SO SCIENTIFIC AMERICAN LA English DT Article C1 MIT, Cambridge, MA 02139 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. RP Langer, RS (reprint author), MIT, Cambridge, MA 02139 USA. NR 3 TC 185 Z9 198 U1 0 U2 20 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD APR PY 1999 VL 280 IS 4 BP 86 EP 89 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 176VF UT WOS:000079172000028 PM 10201120 ER PT J AU Boussiotis, VA Freedman, AS Nadler, LM AF Boussiotis, VA Freedman, AS Nadler, LM TI Bone marrow transplantation for low-grade lymphoma and chronic lymphocytic leukemia SO SEMINARS IN HEMATOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; POLYMERASE CHAIN-REACTION; VERSUS-HOST DISEASE; HIGH-DOSE THERAPY; B-CELL LYMPHOMA; FOLLICULAR LYMPHOMA; MYELODYSPLASTIC SYNDROME; LATE COMPLICATION; TRANSLOCATION; MANAGEMENT C1 Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 50 TC 18 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 1999 VL 36 IS 2 BP 209 EP 216 PG 8 WC Hematology SC Hematology GA 191YM UT WOS:000080049900012 PM 10319389 ER PT J AU Suit, H Spiro, I AF Suit, H Spiro, I TI Radiation treatment of benign mesenchymal disease SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID PIGMENTED VILLONODULAR SYNOVITIS; DESMOID TUMORS; AGGRESSIVE FIBROMATOSIS; VERTEBRAL HEMANGIOMAS; RADIOTHERAPY; MANAGEMENT; THERAPY; BONE; IRRADIATION; EXPERIENCE C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Connect Tissue Oncol Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Suit, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 45 TC 16 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 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD APR PY 1999 VL 9 IS 2 BP 171 EP 178 DI 10.1016/S1053-4296(99)80007-1 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 187ZN UT WOS:000079819100007 PM 10092709 ER PT J AU Rao, PM AF Rao, PM TI CT of diverticulitis and alternative conditions SO SEMINARS IN ULTRASOUND CT AND MRI LA English DT Article ID PRIMARY EPIPLOIC APPENDAGITIS; COLONIC DIVERTICULITIS; BARIUM ENEMA; SIGMOID DIVERTICULITIS; PERCUTANEOUS DRAINAGE; QUADRANT PERITONITIS; COMPUTED-TOMOGRAPHY; CONTRAST MATERIAL; HELICAL CT; DIAGNOSIS C1 Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 31 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0887-2171 J9 SEMIN ULTRASOUND CT JI Semin. Ultrasound CT MRI PD APR PY 1999 VL 20 IS 2 BP 86 EP 93 DI 10.1016/S0887-2171(99)90040-9 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 187AW UT WOS:000079764600005 PM 10222517 ER PT J AU Sheridan, R Schulz, J Ryan, C Ackroyd, F Basha, G Tompkins, R AF Sheridan, R Schulz, J Ryan, C Ackroyd, F Basha, G Tompkins, R TI Percutaneous endoscopic gastrostomy in burn patients SO SURGICAL ENDOSCOPY-ULTRASOUND AND INTERVENTIONAL TECHNIQUES LA English DT Article DE burn patients; percutaneous endoscopic gastrostomy AB Background: Prolonged enteral feedings are required occasionally in seriously burned individuals. We have employed percutaneous endoscopic gastrostomy (PEG) in selected patients who require particularly prolonged access, thus prompting this review. Methods: The PEG procedure was performed under general anesthesia in combination with another surgical procedure using a variety of commercially available needle and guidewire kits in 14 patients. Results: These 14 patients had an average age of 55.2 +/- 6.6 years and a burn involving 38 +/- 8% of the body surface. Eleven of these patients had suffered an inhalation injury. The tubes were placed an average of 57 +/-: 10.5 days after injury through unburned and unharvested skin in four patients (28%), healed donor sites in five patients (35%), healed burn in one patient (1%), and grafted burn in four patients (28%). One patient, whose catheter was placed through a grafted fascial excision, developed moderate local wound erosion. Tubes were known to have been left in place as long as 155 days. However, most were removed in rehabilitation hospitals, and we were unable to determine how long most were left in place. We are unaware of any problems with the tubes occurring after discharge from the acute care setting. Conclusions: In selected patients, PEG can provide more comfortable access for prolonged enteral feedings than nasogastric tubes and can be placed with minimal morbidity. C1 Harvard Univ, Massachusetts Gen Hosp, Shriners Burns Hosp, Dept Surg,Sch Med,Div Burns & Trauma, Boston, MA 02114 USA. RP Sheridan, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Shriners Burns Hosp, Dept Surg,Sch Med,Div Burns & Trauma, Bigelow 1302, Boston, MA 02114 USA. NR 11 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0930-2794 J9 SURG ENDOSC-ULTRAS JI Surg. Endosc.-Ultrason. Interv. Tech. PD APR PY 1999 VL 13 IS 4 BP 401 EP 402 DI 10.1007/s004649900998 PG 2 WC Surgery SC Surgery GA 179WE UT WOS:000079352300019 PM 10094756 ER PT J AU Koenig, F Gonzalez, S White, WM Lein, M Rajadhyaksha, M AF Koenig, F Gonzalez, S White, WM Lein, M Rajadhyaksha, M TI Near-infrared confocal laser scanning microscopy of bladder tissue in vivo SO UROLOGY LA English DT Article ID URINARY-BLADDER; HUMAN SKIN; INVIVO AB Objectives. To assess the potential of a near-infrared confocal laser scanning microscope (CLSM) for imaging bladder tissue in vivo. Methods. Confocal images of the exposed bladder of male Sprague-Dawley rats were obtained with a CLSM. To minimize tissue motion, the bladder was placed in light contact under an objective lens housing, and the top surface was lightly flattened with a coverslip. Images were obtained from the outer and inner layers of the bladder wall with a lateral resolution of 0.5 to 1 mu m and an axial resolution (section thickness) of 3 to 5 mu m. The confocal images were later correlated with routine histologic studies. Results. The CLSM allows imaging of the urothelium, the superficial and deep portions of the lamina propria, the muscularis propria, and the serosa of the bladder wall in vivo. Urothelial cells, collagen bundles and fibers, muscle, and circulating blood cells in capillaries and larger blood vessels are easily visualized. The confocal images correlated well with the histologic studies, Conclusions. Confocal microscopy allows real-time, high-resolution, high-contrast imaging of cellular and structural morphologic features to a maximal depth of 300 mu m within the bladder wall in vivo. Artifacts caused by tissue motion can be minimized with a bladder-objective lens contact housing. (C) 1999, Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Lucid Inc, Henrietta, NY USA. RP Rajadhyaksha, M (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Bartlett Hall Extens 630, Boston, MA 02114 USA. NR 16 TC 27 Z9 27 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD APR PY 1999 VL 53 IS 4 BP 853 EP 857 DI 10.1016/S0090-4295(98)00628-1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 183NK UT WOS:000079559500041 PM 10197874 ER PT J AU Moriarty, HJ Deatrick, JA Mahon, MM Feetham, SL Carroll, RM Shepard, MP Orsi, AJ AF Moriarty, HJ Deatrick, JA Mahon, MM Feetham, SL Carroll, RM Shepard, MP Orsi, AJ TI Issues to consider when choosing and using large national databases for research of families SO WESTERN JOURNAL OF NURSING RESEARCH LA English DT Article AB Secondary analysis of large national databases offers promise for research of families. In this article issues that the secondary analyst must consider when choosing a database for research of families are described. Potential advantages and limitations of databases are discussed. Strategies to minimize potential limitations are highlighted. C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Villanova Univ, Villanova, PA 19085 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Illinois, Chicago, IL USA. Salisbury State Univ, Salisbury, MD USA. Temple Univ, Philadelphia, PA 19122 USA. RP Moriarty, HJ (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NR 20 TC 14 Z9 16 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0193-9459 J9 WESTERN J NURS RES JI West. J. Nurs. Res. PD APR PY 1999 VL 21 IS 2 BP 143 EP 153 DI 10.1177/01939459922043794 PG 11 WC Nursing SC Nursing GA 184JL UT WOS:000079608100003 PM 11512173 ER PT J AU Ayre, BG Kohler, U Goodman, HM Haseloff, J AF Ayre, BG Kohler, U Goodman, HM Haseloff, J TI Design of highly specific cytotoxins by using trans-splicing ribozymes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROUP-I INTRON; ACTIVE-SITE MUTATIONS; DIPHTHERIA-TOXIN; MAMMALIAN-CELLS; MEDIATED REPAIR; RNA; SEQUENCE; MESSENGER; EXPRESSION; YEAST AB We have designed ribozymes based on a self-splicing group I intron that can trans-splice exon sequences into a chosen RNA target to create a functional chimeric mRNA and provide a highly specific trigger for gene expression. We have targeted ribozymes against the coat protein mRNA of a widespread plant pathogen, cucumber mosaic virus, The ribozymes were designed to trans-splice the coding sequence of the diphtheria toxin A chain in frame with the viral initiation codon of the target sequence. Diphtheria toxin A chain catalyzes the ADP ribosylation of elongation factor 2 and can cause the cessation of protein translation. In a Saccharomyces cerevisiae model system, ribozyme expression was shown to specifically inhibit the growth of cells expressing the virus mRNA. A point mutation at the target splice site alleviated this ribozyme-mediated toxicity. Increasing the extent of base pairing between the ribozyme and target dramatically increased specific expression of the cytotoxin and reduced illegitimate toxicity invivo. Trans-splicing ribozymes may provide a new class of agents for engineering virus resistance and therapeutic cytotoxins. C1 MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Haseloff, J (reprint author), MRC, Mol Biol Lab, Hills Rd, Cambridge CB2 2QH, England. EM jph@mrc-lmb.cam.ac.uk OI Haseloff, Jim/0000-0003-4793-8058 NR 38 TC 41 Z9 41 U1 2 U2 2 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 MAR 30 PY 1999 VL 96 IS 7 BP 3507 EP 3512 DI 10.1073/pnas.96.7.3507 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 182PT UT WOS:000079507900031 PM 10097066 ER PT J AU Kim, JI Li, TS Ho, IC Grusby, MJ Glimcher, LH AF Kim, JI Li, TS Ho, IC Grusby, MJ Glimcher, LH TI Requirement for the c-Maf transcription factor in crystallin gene regulation and lens development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HOMEOBOX-CONTAINING GENE; EYE DEVELOPMENT; BETA-CRYSTALLIN; EYELESS GENE; EXPRESSION; MOUSE; INDUCTION; PROTEINS; DNA; DIFFERENTIATION AB The vertebrate lens is a tissue composed of terminally differentiated fiber cells and anterior lens epithelial tells. The abundant, preferential expression of the soluble proteins called crystallins creates a transparent, refractive index gradient in the lens. Several transcription factors such as Pax6, Sox1, and L-Maf have been shown to regulate lens development Here we show that mice lacking the transcription factor c-Maf are microphthalmic secondary to defective lens formation, specifically from the failure of posterior lens fiber elongation. The marked impairment of crystallin gene expression observed is likely explained by the ability of c-Maf to transactivate the crystallin gene promoter, Thus, c-Maf is required for the differentiation of the vertebrate lens. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Glimcher, LH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, 651 Huntington Ave,FXB-2, Boston, MA 02115 USA. EM LGlimche@HSPH.Harvard.Edu FU NIAID NIH HHS [AI/AG 37833, P01 AI037833] NR 41 TC 156 Z9 159 U1 0 U2 4 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 MAR 30 PY 1999 VL 96 IS 7 BP 3781 EP 3785 DI 10.1073/pnas.96.7.3781 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 182PT UT WOS:000079507900079 PM 10097114 ER PT J AU Lee, JT Lu, NF Han, Y AF Lee, JT Lu, NF Han, Y TI Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHROMOSOME INACTIVATION; XIST GENE; INSITU HYBRIDIZATION; PROMOTER REGION; STEM-CELLS; EXPRESSION; YAC; DNA; INTERPHASE; INITIATION AB Dosage compensation in mammals occurs by ii inactivation, a silencing mechanism regulated in cis by the X inactivation center (Xic), In response to developmental cues, the Xic orchestrates events of X inactivation, including chromosome counting and choice, initiation, spread, and establishment of silencing. It remains unclear what elements make up the Xic. We previously showed that the Xic is contained within a 450-kb sequence that includes Xist, an RNA encoding gene required for X inactivation. To characterize the Xic further, we performed deletional analysis across the 450-kb region by yeast-artificial-chromosome fragmentation and phage P1 cloning. We tested Xic deletions for cis inactivation potential by using a transgene (Tg)-based approach and found that an 80-kb subregion also enacted somatic X inactivation on autosomes, Xist RNA coated the autosome but skipped the Xic Tg, raising the possibility that X chromosome domains escape inactivation by excluding Xist RNA binding, The autosomes became late-replicating and hypoacetylated on histone H4. A deletion of the Xist 5' sequence resulted in the loss of somatic X inactivation without abolishing Xist expression in undifferentiated cells. Thus, Xist expression in undifferentiated cells can be separated genetically from somatic silencing. Analysis of multiple Xic constructs and insertion sites indicated that long-range Xic effects can be generalized to different autosomes, thereby supporting the feasibility of a Tg-based approach for studying X inactivation. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu NR 38 TC 87 Z9 90 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 MAR 30 PY 1999 VL 96 IS 7 BP 3836 EP 3841 DI 10.1073/pnas.96.7.3836 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 182PT UT WOS:000079507900089 PM 10097124 ER PT J AU Tsiokas, L Arnould, T Zhu, CW Kim, E Walz, G Sukhatme, VP AF Tsiokas, L Arnould, T Zhu, CW Kim, E Walz, G Sukhatme, VP TI Specific association of the gene product of PKD2 with the TRPC1 channel SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CAPACITATIVE CALCIUM-ENTRY; POLYCYSTIC KIDNEY-DISEASE; STORE-OPERATED CHANNEL; MOLECULAR-BASIS; DROSOPHILA TRP; CA2+ CHANNELS; PROTEIN; EXPRESSION; CLONING; HOMOLOG AB The function(s) of the genes (PKD1 and PKD2) responsible for the majority of cases of autosomal dominant polycystic kidney disease is unknown. While PKD1 encodes a large integral membrane protein containing several structural motifs found in known proteins involved in cell-cell or cell-matrix interactions, PKD2 has homology to PKD1 and the major subunit of the voltage-activated Ca2+ channels. We now describe sequence homology between PKD2 and various members of the mammalian transient receptor potential channel (TRPC) proteins, thought to be activated by G protein-coupled receptor activation and/or depletion of internal Ca2+ stores. We show that PKD2 can directly associate with TRPC1 but not TRPC3 in transfected cells and in vitro. This association is mediated by two distinct domains in PKD2, One domain involves a minimal region of 73 amino acids in the C-terminal cytoplasmic tail of PKD2 shown previously to constitute an interacting domain with PKD1, However, distinct residues within this region mediate specific interactions with TRPC1 or PKD1. The C-terminal domain is sufficient but not necessary for the PKD2-TRPC1 association. A more N-terminal domain located within transmembrane segments S2 and S5, including a putative pore helical region between S5 and S6, is also responsible for the association. Given the ability of the TRPC to form functional homo- and heteromultimeric complexes, these data provide evidence that PKD2 may be functionally related to TRPC proteins and suggest a possible role of PKD2 in modulating Ca2+ entry in response to G protein-coupled receptor activation and/or store depletion. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA. RP Sukhatme, VP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. EM vsukhatm@bidmc.harvard.edu FU NIDDK NIH HHS [F32 DK009625, DK-09625]; NIMH NIH HHS [MH-01147] NR 39 TC 231 Z9 245 U1 1 U2 2 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 MAR 30 PY 1999 VL 96 IS 7 BP 3934 EP 3939 DI 10.1073/pnas.96.7.3934 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 182PT UT WOS:000079507900106 PM 10097141 ER PT J AU Demetri, GD Fletcher, CDM Mueller, E Sarraf, P Naujoks, R Campbell, N Spiegelman, BM Singer, S AF Demetri, GD Fletcher, CDM Mueller, E Sarraf, P Naujoks, R Campbell, N Spiegelman, BM Singer, S TI Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nuclear receptors; sarcoma; drug development; oncology; antineoplastic ID ACUTE PROMYELOCYTIC LEUKEMIA; PPAR-GAMMA; MYXOID LIPOSARCOMA; TERMINAL DIFFERENTIATION; HIGH-RESOLUTION; TISSUE; CHEMOTHERAPY; EXPRESSION; GRADIENT; PROTEIN AB Agonist ligands for the nuclear receptor peroxisome proliferator-activated receptor-gamma have been shown to induce terminal differentiation of normal preadipocytes and human liposarcoma cells in vitro. Because the differentiation status of liposarcoma is predictive of clinical outcomes, modulation of the differentiation status of a tumor may favorably impact clinical behavior. We have conducted a clinical trial for treatment of patients with advanced liposarcoma by using the peroxisome proliferator-activated receptor-gamma ligand troglitazone, in which extensive correlative laboratory studies of tumor differentiation were performed. We report here the results of three patients with intermediate to high-grade liposarcomas in whom troglitazone administration induced histologic and biochemical differentiation in vivo. Biopsies of tumors from each of these patients while on troglitazone demonstrated histologic evidence of extensive lipid accumulation by tumor cells and substantial increases in NMR-detectable tumor triglycerides compared with pretreatment biopsies. In addition, expression of several mRNA transcripts characteristic of differentiation in the adipocyte lineage was induced. There was also a marked reduction in immunohistochemical expression of Ki-67, a marker of cell proliferation. Together, these data indicate that terminal adipocytic differentiation was induced in these malignant tumors by troglitazone. These results indicate that lineage-appropriate differentiation can be induced pharmacologically in a human solid tumor. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA75720-01] NR 30 TC 372 Z9 382 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 MAR 30 PY 1999 VL 96 IS 7 BP 3951 EP 3956 DI 10.1073/pnas.96.7.3951 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 182PT UT WOS:000079507900109 PM 10097144 ER PT J AU Marshall, WL Datta, R Hanify, K Teng, E Finberg, RW AF Marshall, WL Datta, R Hanify, K Teng, E Finberg, RW TI U937 cells overexpressing bcl-xl are resistant to human immunodeficiency virus-1-induced apoptosis and human immunodeficiency virus-1 replication SO VIROLOGY LA English DT Article ID NF-KAPPA-B; TAT PROTEIN; HIV-1 TAT; T-CELLS; INFECTION; DEATH; EXPRESSION; INDUCTION; ACTIVATION; MECHANISM AB Many viruses, including human immunodeficiency virus type 1 (HIV-1), induce apoptosis and are affected by cellular expression of antiapoptotic genes. We sought to examine the effect of antiapoptotic gene expression on HIV replication by transfecting the promyelomonocytic cell line U937 with the bcl-xl gene to obtain clones of U937 cells that overexpressed bcl-xl (designated U937bcl-xl), a negative control U937 clone transfected with vector alone (designated U937neo) and a clone overexpressing bcl-2 (designated U937bcl-2). After infection with HIV-1, U937neo cells underwent apoptosis four times as frequently as the U937bcl-xl cells. Furthermore, U937bcl-xl cells produced 5-fold less HIV-I protein than U937neo, whereas U937bcl-2 produced at least 2-fold more p24 than the U937neo control. Transient coexpression of bcl-2 or bcl-xl decreased HIV production and transcription from the HIV LTR. To define the mechanism by which bcl-xl, but not bcl-2, inhibits HIV expression, we examined bcl-2 and bcl-xl expression after HIV infection and CD4 cross-linking. Although HIV-I infection or cross-linking CD4 led to a decrease in expression of bcl-2, it had no effect on bcl-xl expression. These results provide a mechanism for the resistance of U937bcl-xl transfectants, but not U937bcl-2 transfectants, to HIV-1 replication in monocytic cells in vitro. Therapies that up-regulate bcl-xl expression potentially provide a novel means to decrease the destructiveness Of HIV-1. (C) 1999 Academic Press. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Marshall, WL (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI01078-03, AI28691-06] NR 28 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 1999 VL 256 IS 1 BP 1 EP 7 DI 10.1006/viro.1999.9599 PG 7 WC Virology SC Virology GA 184MK UT WOS:000079615800001 PM 10087220 ER PT J AU Reimann, KA Watson, A Dailey, PJ Lin, WY Lord, CI Steenbeke, TD Parker, RA Axthelm, MK Karlsson, GB AF Reimann, KA Watson, A Dailey, PJ Lin, WY Lord, CI Steenbeke, TD Parker, RA Axthelm, MK Karlsson, GB TI Viral burden and disease progression in rhesus monkeys infected with chimeric simian-human immunodeficiency viruses SO VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEINS; LYMPHOCYTE DEPLETION; MACAQUES; ISOLATE; TYPE-1; AIDS; REPLICATION; ANTIBODY; PLASMA; LOAD AB To determine the role of viral burden in simian-human immunodeficiency virus (SHIV)-induced disease, cellular provirus and plasma viral RNA levels were measured after inoculation of rhesus monkeys with four different SHIVs. These SHIVs included SHIV-HXBc2 and SHIV-89.6, constructed with env, tat, rev, and vpu derived from either cell line-passaged or primary patient isolates of human immunodeficiency virus type 1;the viral quasispecies SHIV-89.6P derived after in vivo passage of SHIV-89.6; and a molecular clone, SHIV-KB9, derived from SHIV-89.6P. SHIV-HXBc2 and SHIV-89.6 are nonpathogenic in rhesus monkeys; SHIV-89.6P and SHIV-KBS cause rapid CD4(+) T cell depletion and an immunodeficiency syndrome. Relative SHIV provirus levels were highest during primary infection in monkeys infected with SHIV-89.6P, the virus that caused the most rapid and dramatic CD4(+) T cell depletion. However, by 10 weeks postinoculation, provirus levels were similar in monkeys infected with the pathogenic and nonpathogenic chimeric viruses. The virus infections that resulted in the highest peak and chronic viral RNA levels were the pathogenic viruses SHIV-89.6P and SHIV-KBS. SHIV-89.6P uniformly caused rapid and profound CD4(+) T cell depletion and immunodeficiency. Infection with the SHIV-KBS resulted in very low CD4(+) T cell counts without seroconversion in some monkeys and a substantial but less profound CD4(+) T cell depletion and rapid seroconversion in others. Surprisingly, the level of plasma viremia did not differ between SHIV-KB9-infected animals exhibiting these contrasting outcomes, suggesting that host factors may play an important role in AIDS virus pathogenesis. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Biometr Ctr, Boston, MA 02215 USA. Bristol Myers Squibb Co, Princeton, NJ 08543 USA. Chiron Corp, Diagnost, Emeryville, CA 94608 USA. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Reimann, KA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, RE-113,POB 15732, Boston, MA 02215 USA. FU NCRR NIH HHS [RR-13150]; NHLBI NIH HHS [HL-59747]; NIAID NIH HHS [AI-33832] NR 20 TC 44 Z9 44 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 30 PY 1999 VL 256 IS 1 BP 15 EP 21 DI 10.1006/viro.1999.9632 PG 7 WC Virology SC Virology GA 184MK UT WOS:000079615800003 PM 10087222 ER PT J AU Ferrante, RJ Hantraye, P Brouillet, E Beal, MF AF Ferrante, RJ Hantraye, P Brouillet, E Beal, MF TI Increased nitrotyrosine immunoreactivity in substantia nigra neurons in MPTP treated baboons is blocked by inhibition of neuronal nitric oxide synthase SO BRAIN RESEARCH LA English DT Article DE MPTP; 3-nitrotyrosine; Parkinson's disease; nitric oxide; peroxynitrite ID SUPEROXIDE-DISMUTASE; PARKINSONS-DISEASE; NEUROTOXICITY; PEROXYNITRITE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 7-NITROINDAZOLE; NITRATION; MICE AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathologic changes reminiscent of those which occur in idiopathic Parkinson's disease. 7-Nitroindazole (7-NI) is a relatively selective inhibitor of the neuronal isoform of nitric oxide synthase. We previously demonstrated that administration of 7-NI is effective in blocking MPTP toxicity in both mice and baboons. This was suggested to be due to inhibition of the generation of peroxynitrite which can nitrate tyrosines. In the present study we found increased 3-nitrotyrosine immunoreactivity in the substantia nigra of MPTP treated baboons, which was blocked by coadministration of 7-NI. These findings provide further evidence that peroxynitrite may play a role in MPTP induced parkinsonism in baboons. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Neurol Serv Warren 408, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Vet Affairs Med Ctr, Geriatr Res Educ Clin Ctr, Bedford, MA USA. CEA, Serv Hosp Frederic Joliot, CNRS 2210, URA, F-91406 Orsay, France. Massachusetts Gen Hosp, Neurochem Lab, Serv Neurol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurol Serv Warren 408, Neurochem Lab, Boston, MA 02114 USA. RI Brouillet, Emmanuel/B-4784-2014 OI Brouillet, Emmanuel/0000-0001-6322-7403 FU NINDS NIH HHS [NS16367, NS31579, NS37102] NR 24 TC 71 Z9 73 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 MAR 27 PY 1999 VL 823 IS 1-2 BP 177 EP 182 DI 10.1016/S0006-8993(99)01166-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA 179QP UT WOS:000079340400019 PM 10095024 ER PT J AU Mitsikostas, DD del Rio, MS Moskowitz, MA Waeber, C AF Mitsikostas, DD del Rio, MS Moskowitz, MA Waeber, C TI Both 5-HT1B and 5-HT1F receptors modulate c-fos expression within rat trigeminal nucleus caudalis SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE c-fos; nociception; 5-HT1B receptor; 5-HT1F receptor; migraine; sumatriptan ID NEUROGENIC PLASMA EXTRAVASATION; GUINEA-PIG; MESSENGER-RNA; DURA-MATER; 5-HYDROXYTRYPTAMINE(1B) RECEPTORS; DIFFERENTIAL DISTRIBUTION; PROTEIN EXTRAVASATION; ANTIMIGRAINE DRUGS; BLOOD-VESSELS; BINDING-SITES AB A possible mechanism of action of antimigraine drugs such as sumatriptan is inhibition of the trigeminovascular pathway. sumatriptan's effects might be mediated by 5-HT1B, 5-HT1D or 5-HT1F receptors. To establish the relative importance of these subtypes, we compared the effects of sumatriptan with those of a selective 5-HT1F receptor agonist (LY 344864) on c-fos protein expression in the trigeminal nucleus caudalis. c-fos expression was induced in urethane-anaesthetized rats by intracisternal capsaicin administration. Sumatriptan and LY 344864 decreased the number of capsaicin-induced c-fos-like immunoreactive cells within trigeminal nucleus caudalis (ID50 = 0.04 and 0.6 mg kg(-1)). The effect of sumatriptan, but not of LY 344864, was prevented by pretreatment with the antagonist SDZ 21-009, which displays high affinity for rat 5-HT1B receptors. LY 344864 appears to attenuate c-fos-like immunoreactivity via 5-HT1F receptors, while sumatriptan acts via 5-HT1B receptors. The fact that activation of 5-HT1F receptors is sufficient to modulate the activity of the trigeminal system suggests that this receptor may be a target for antimigraine drugs with improved safety profile. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. RP Waeber, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke & Neurovasc Regulat Lab, 149 13th St,CNY-6403, Boston, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [NS 35611] NR 42 TC 39 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 26 PY 1999 VL 369 IS 3 BP 271 EP 277 DI 10.1016/S0014-2999(99)00067-9 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 183FD UT WOS:000079542800003 PM 10225363 ER PT J AU Pandey, P Avraham, S Place, A Kumar, V Majumder, PK Cheng, KD Nakazawa, A Saxena, S Kharbanda, S AF Pandey, P Avraham, S Place, A Kumar, V Majumder, PK Cheng, KD Nakazawa, A Saxena, S Kharbanda, S TI Bcl-x(L) blocks activation of related adhesion focal tyrosine kinase proline-rich tyrosine kinase 2 and stress-activated protein kinase c-Jun N-terminal protein kinase in the cellular response to methylmethane sulfonate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; KAPPA-B ACTIVATION; INDUCED APOPTOSIS; DEATH PATHWAY; POLY(ADP-RIBOSE) POLYMERASE; PROTEOLYTIC ACTIVATION; JNK ACTIVATION; BCL-2; CELLS; INDUCTION AB The stress-activated protein kinase/c-Jun N-terminal protein kinase (JNK) is induced in response to ionizing radiation and other DNA-damaging agents. Recent studies indicate that activation of JNK is necessary for induction of apoptosis in response to diverse agents. Here we demonstrate that methylnethane sulfonate (MMS)-induced activation of JNK is inhibited by overexpression of the anti-apoptotic protein Bcl-x(L), but not by caspase inhibitors CrmA and p35, By contrast, UV-induced JNK activity is insensitive to Bcl-x(L). The results demonstrate that treatment with MMS is associated with an increase in tyrosine phosphorylation of related adhesion focal tyrosine kinase (RAFTK)/proline-rich tyrosine kinase 2 (PYK2), an upstream effector of JNK and that this phosphorylation is inhibited by overexpression of Bcl-x(L). Furthermore, overexpression of a dominant-negative mutant of RAFTK (RAFTK K-M) inhibits MMS-induced JNK activation, The results indicate that inhibition of RAFTK phosphorylation by MMS in Bcl-x(L) cells is attributed to an increase in tyrosine phosphatase activity in these cells. Hence, treatment of Bcl-x(L) cells with sodium vanadate, a tyrosine phosphatase inhibitor, restores MMS-induced activation of RAFTK and JNK. These findings indicate that RAFTK-dependent induction of JNK in response to MMS is sensitive to Bcl-x(L), but not to CrmA. and p35, by a mechanism that inhibits tyrosine phosphorylation and thereby activation of RAFTK. Taken together, these findings support a novel role for Bcl-x(L) that is independent of the caspase cascade. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med & Hematol Oncol, Boston, MA 02115 USA. Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75216]; NHLBI NIH HHS [HL55445] NR 60 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 26 PY 1999 VL 274 IS 13 BP 8618 EP 8623 DI 10.1074/jbc.274.13.8618 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181PV UT WOS:000079451600040 PM 10085098 ER PT J AU Gusella, JF Ramesh, V MacCollin, M Jacoby, LB AF Gusella, JF Ramesh, V MacCollin, M Jacoby, LB TI Merlin: the neurofibromatosis 2 tumor suppressor SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID TRANSMEMBRANE CONDUCTANCE REGULATOR; BILATERAL ACOUSTIC NEUROFIBROMATOSIS; EZRIN/RADIXIN/MOESIN ERM PROTEINS; BORDER NA+/H+ EXCHANGER; AMINO-TERMINAL DOMAIN; TYPE-2 NF2 GENE; BETA(2)-ADRENERGIC RECEPTOR; FUNCTIONAL DOMAINS; PLASMA-MEMBRANE; ACTIN-BINDING C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. FU NINDS NIH HHS [NS24279] NR 49 TC 52 Z9 53 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD MAR 25 PY 1999 VL 1423 IS 2 BP M29 EP M36 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 186ZY UT WOS:000079762500003 PM 10214350 ER PT J AU Rosowsky, A Papoulis, AT Forsch, RA Queener, SF AF Rosowsky, A Papoulis, AT Forsch, RA Queener, SF TI Synthesis and antiparasitic and antitumor activity of 2,4-diamino-6-(arylmethyl)-5,6,7,8-tetrahydroquinazoline analogues of piritrexim SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article; Proceedings Paper CT 10th NCI-EORTC Symposium on New Drugs in Cancer Therapy CY JUN 16-19, 1998 CL AMSTERDAM, NETHERLANDS ID GONDII DIHYDROFOLATE-REDUCTASE; PNEUMOCYSTIS-CARINII PNEUMONIA; IRREVERSIBLE ENZYME-INHIBITORS; TOXOPLASMA-GONDII; TRIMETHOPRIM-SULFAMETHOXAZOLE; CHOLINE ACETYLTRANSFERASE; ANTIFOLATE ACTIVITY; TRIMETREXATE; ANTIPNEUMOCYSTIS; POTENT AB Nineteen previously undescribed 2,4-diamino-6-(arylmethyl)-5,6,7, 8-tetrahydroquinazolines (5a-m, 10-12) were synthesized as part of a larger effort to assess the therapeutic potential of lipophilic dihydrofolate reductase (DHFR) inhibitors against opportunistic infections of AIDS. Condensation of appropriately substituted (arylmethyl)triphenylphosphoranes with 4,4-ethylenedioxycyclohexanone, followed by hydrogenation (H-2/Pd-C) and acidolysis, yielded the corresponding 4-(arylmethyl)cyclohexanones, which were then condensed with cyanoguanidine to form the tetrahydroquinazolines. Three simple 2,4-diamino-6-alkyl-5,6,7,8-tetrahydroquinazoline model compounds (9a-c) were also prepared in one step from commercially available 4-alkylcyclohexanones by this method. Enzyme inhibition assays against rat liver DHFR, Pneumocystis carinii DHFR, and the bifunctional DHFR-TS enzyme from Toxoplasma gondii were carried out, and the selectivity ratios IC50(rat)/IC50(P. carinii) and IC50(rat)/IC50-(T. gondii) were compared. The three most potent inhibitors of P. carinii DHFR were the 2,5-dimethoxybenzyl (5j), 3,4-dimethoxybenzyl (5k), and 3,4,5-trimethoxybenzyl (51) analogues, with IC50 values of 0.057, 0.10, and 0.091 mu M, respectively. The remaining compounds generally had IC50 values in the 0.1-1.0 mu M range. However all the compounds were more potent against the rat liver enzyme than the P. carinii enzyme and thus were nonselective. The T. gondii enzyme was always more sensitive than the P. carinii enzyme, with most of the analogues giving IC50 values of 0.01-0.1 mu M. Moderate 5-10-fold selectivity for T. gondii versus rat liver DHFR was observed with five compounds, the best combination of potency and selectivity being achieved with the 2-methoxybenzyl analogue 5d, which had an IC50 Of 0.014 mu M and a selectivity ratio of 8.6. One compound (51) was tested for antiproliferative activity against P. carinii trophozoites in culture at a concentration of 10 mu g/mL and was found to completely suppress growth over 7 days. The suppressive effect of 51 was the same as that of trimethoprim (10 mu g/mL) + sulfamethoxazole (250 mu g/mL), a standard clinical combination for the treatment of P. carinii pneumonia in AIDS patients. Four compounds (5a,h,k,l) were tested against T. gondii tachyzoites in culture and were found to have a potency (IC50 = 0.1-0.5 mu M) similar to that of pyrimethamine (IC50 = 0.69 mu M), a standard clinical agent for the treatment of cerebral toxoplasmosis in AIDS patients. Compound 5h was also active against T. gondii infection in mice when given qdx8 by peritoneal injection at doses ranging from 62.5 (initial dose) to 25 mg/kg. Survival was prolonged to the same degree as with 25 mg/kg clindamycin, another widely used drug against toxoplasmosis. Three compounds (5j-l) were tested for antiproliferative activity against human tumor cells in culture. Among the 25 cell lines in the National Cancer Institute panel for which data were confirmed in two independent experiments, the IC50 for at least two of these compounds was <10 mu M against 17 cell lines (68%) and in the 0.1-1 mu M range against 13 cell lines (52%). One compound (5j) had an IC50 Of <0.01 mu M against four of the cell lines. The activity profiles of 5k,l were generally similar to that of 5j except that there were no cells against which the IC50 was < 0.01 mu M. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [N01-AI35171, R01-AI29904] NR 37 TC 43 Z9 45 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 25 PY 1999 VL 42 IS 6 BP 1007 EP 1017 DI 10.1021/jm980572i PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 181CW UT WOS:000079423900009 PM 10090784 ER PT J AU Chaudhuri, A Orme, S Vo, T Wang, WH Cherayil, BJ AF Chaudhuri, A Orme, S Vo, T Wang, WH Cherayil, BJ TI Phosphorylation of TRAF2 inhibits binding to the CD40 cytoplasmic domain SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID THIN-LAYER CHROMATOGRAPHY; NF-KAPPA-B; PROTEIN; ACTIVATION; KINASE; IDENTIFICATION; FAMILY; CELLS AB TRAF2 is a signal transducing adaptor molecule which binds to the CD40 cytoplasmic domain. We have found that it is phosphorylated, predominantly on serine residues, when transiently overexpressed in 293 cells. The phosphorylation appears to be related to the signaling events that are activated by TRAF2 under these circumstances, since two nonfunctional mutants were found to be phosphorylated significantly less than the wild-type protein.,Furthermore, the phosphorylation status of TRAF2:had significant effects Oh the ability of the protein to bind to CD40, as evidenced by our observations that the CD40 cytoplasmic domain interacted preferentially with underphosphorylated TRAF2 and that phosphatase treatment significantly enhanced the binding of TRAF2 to CD40. We conclude from these studies that the phosphorylation of TRAFB is likely to play an important role in regulating Signaling by virtue of its ability to influence the CD40-TRAF2 interaction. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brandeis Univ, Dept Biol, Waltham, MA 02254 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA66626]; NIDDK NIH HHS [T-32-DK-07477] NR 18 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 24 PY 1999 VL 256 IS 3 BP 620 EP 625 DI 10.1006/bbrc.1999.0385 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 182KW UT WOS:000079499000031 PM 10080948 ER PT J AU Weissman, JS Saglam, D Campbell, EG Causino, N Blumenthal, D AF Weissman, JS Saglam, D Campbell, EG Causino, N Blumenthal, D TI Market forces and unsponsored research in academic health centers SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MANAGED CARE; CLINICAL RESEARCH; LIFE-SCIENCE; FACULTY; MEDICINE; IMPACT AB Context Increased competitive pressures on academic health centers may result in reduced discretionary funds from patient care revenues to support the performance of unsponsored research, including institutionally funded and faculty-supported activities. Objective To measure the amount and distribution of unsponsored research activities and their outcomes. Design and Setting Survey conducted in academic year 1996-1997 of 2336 research faculty in 117 medical schools. Responses were weighted to provide national estimates. Main Outcome Measures Institutionally funded research as a proportion of total direct costs of research was compared across stages of market competition. Logistic regression was used to assess the relationship of performing unsponsored research to faculty characteristics and market stage. Results Overall, 43% of faculty received institutional funding for research. Young faculty were more likely than others to receive institutional support (adjusted odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.9; P = .004). The amount of institutional support as a proportion of total funding was more than twice as high in less competitive markets (6.1 %) compared with the most competitive markets (2.5%; P = .05). Most faculty (55%) performed faculty-supported research. Clinical researchers (OR, 1.6; 95% CI, 1.1-2.3), principal investigators (OR, 4.3; 95% CI, 2.8-7.0), faculty with high levels of research effort (OR, 6.2; 95% CI, 4.0-9.5) or institutional funding (OR, 1.9; 95% CI, 1.4-2.6), and faculty in the most competitive markets (OR, 1.9; 95% CI, 1.4-2.5) were more likely than others to conduct faculty-supported research. When undertaken by clinical researchers, these activities were supported by clinical income, extra hours worked, and discretionary funds, and often led to publications (76%) or grant awards (51%). Conclusions Many academic health center faculty receive institutional support to conduct their research or fund the research themselves. Market pressures may be affecting the level of institutional funding available to faculty. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, Partners Healthcare Syst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, Partners Healthcare Syst, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 20 TC 55 Z9 55 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 24 PY 1999 VL 281 IS 12 BP 1093 EP 1098 DI 10.1001/jama.281.12.1093 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 177EP UT WOS:000079197100030 PM 10188659 ER PT J AU Irwin, MW Mak, S Mann, DL Qu, R Penninger, JM Yan, A Dawood, F Wen, WH Shou, ZP Liu, P AF Irwin, MW Mak, S Mann, DL Qu, R Penninger, JM Yan, A Dawood, F Wen, WH Shou, ZP Liu, P TI Tissue expression and immunolocalization of tumor necrosis factor-alpha in postinfarction dysfunctional myocardium SO CIRCULATION LA English DT Article DE tissue; myocardium; infarction; heart failure; remodeling; cytokines; tumor necrosis factor ID ADULT FELINE MYOCARDIUM; CHRONIC HEART-FAILURE; CARDIAC MYOCYTES; FACTOR RECEPTORS; CYTOKINE EXPRESSION; PROTEIN EXPRESSION; PULMONARY-EDEMA; MESSENGER-RNA; INFARCTION; APOPTOSIS AB Background-Tumor necrosis factor-alpha (TNF-alpha) is markedly elevated in advanced heart failure. It is not known whether tissue TNF-alpha is elevated in the common setting of myocardial infarction leading to heart failure and what the source of TNF-alpha is. To determine this, we studied the expression and protein localization of TNF-alpha and its 2 main receptors (TNF-R1/R2) in a rat model of large infarction, Methods and Results-Male rats were randomized to proximal left anterior descending ligation, The animals were killed on days 1, 3, 10, and 35 after ligation to examine gene expression and protein production of TNF-alpha and TNF-R1/R2 from the infarct, peri-infarct, and contralateral zones of infarcted heart. There was increased TNF-alpha mRNA production throughout the myocardium at day I, and detectable expression persisted to day 35 after myocardial infarction. The expression of this cytokine is not confined strictly to the infarct or peri-infarct zones but is expressed by cardiac myocytes within the myocardium in the contralateral normal zone. Changes in gene expression are mirrored initially by augmented protein production within the myocytes. Levels of TNF-alpha protein in the infarct and peri-infarct zones rose early to 8- to 10-fold above normal levels and rose to 4- to 5-fold in the contralateral zone. Finally, expression of the TNF-R1 mRNA transcripts was upregulated at days 3 and 10 after ligation in the infarct and peri-infarct zones, suggesting that the signal transduction pathways necessary for TNF-alpha in the heart remain intact as TNF-alpha biosynthesis increases. Conclusions-TNF-alpha is present early in a model of large myocardial infarction and is sustained into the later stage within the myocardium, Expression of this cytokine is not only confined strictly to the infarct or peri-infarct zone but is expressed by cardiac myocytes within the myocardium contralateral to the infarct. Therefore TNF-alpha production forms a part of an important intrinsic myocardial stress response system to injury. C1 Toronto Hosp, Gen Div, Cardiovasc Res Ctr, Toronto, ON M5G 2C4, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Dept Immunol, Toronto, ON, Canada. Univ Toronto, Ontario Canc Inst, Amgen Inst, Toronto, ON, Canada. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. RP Liu, P (reprint author), Toronto Hosp, Gen Div, Cardiovasc Res Ctr, 12 EC-324, Toronto, ON M5G 2C4, Canada. RI Penninger, Josef/I-6860-2013; Mak, Susanna/C-4617-2015 OI Penninger, Josef/0000-0002-8194-3777; NR 37 TC 264 Z9 295 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 23 PY 1999 VL 99 IS 11 BP 1492 EP 1498 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 176YJ UT WOS:000079179700018 PM 10086975 ER PT J AU Mendola, JD Rizzo, JF Cosgrove, GR Cole, AJ Black, P Corkin, S AF Mendola, JD Rizzo, JF Cosgrove, GR Cole, AJ Black, P Corkin, S TI Visual discrimination after anterior temporal lobectomy in humans SO NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; OBJECT RECOGNITION; AREA V4; LESIONS; PERCEPTION; CORTEX; ACHROMATOPSIA; MONKEY; DISSOCIATION; IMPAIRMENT AB Objective: To determine whether right anterior temporal lobectomy (RTL) results in perceptual deficits, and whether the perception of particular stimulus features (i.e., shape, motion, color) is affected differentially. Background: RTL results in abnormal visual discrimination, recognition, and recall of pictorial material that cannot be easily specified verbally, such as designs and faces. It is unclear whether stimuli must be conceptually meaningful to elicit perceptual deficits. Methods: Tests were constructed to assess a wide spectrum of basic visual discrimination abilities with simple, meaningless stimuli. The performance of nine patients who underwent left temporal lobectomy (LTL) and nine patients who underwent RTL were compared with that of normal control individuals. The mean excision size along lateral cortex was 3.7 cm for the LTL group and 5.6 cm for the RTL group; mean mesial excision size was 5.2 cm for LTL and 4.6 cm for RTL. Results: Basic visual discrimination capacities were demonstrated to be essentially intact after LTL and RTL, except for a mild loss of blue color discrimination after RTL. Conclusions: There is little evidence that RTL produces perceptual impairments limited to the domain of pattern perception, or generalizable to nonmeaningful stimuli. The perceptual loss after RTL may be largely restricted to extraction of meaning, and related to the disruption of the circuits that connect the outcome of visual analysis to previously stored semantic information. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA USA. MIT, Clin Res Ctr, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Mendola, JD (reprint author), MGH NMR Ctr, 149 13th St 2301, Charlestown, MA 02129 USA. FU NCRR NIH HHS [RR00088]; NIGMS NIH HHS [T32GM07484]; NIMH NIH HHS [T32MH15761] NR 40 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 23 PY 1999 VL 52 IS 5 BP 1028 EP 1037 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 182UQ UT WOS:000079516900023 PM 10102424 ER PT J AU Montine, TJ Beal, MF Robertson, D Cudkowicz, ME Biaggioni, I O'Donnell, H Zackert, WE Roberts, LJ Morrow, JD AF Montine, TJ Beal, MF Robertson, D Cudkowicz, ME Biaggioni, I O'Donnell, H Zackert, WE Roberts, LJ Morrow, JD TI Cerebrospinal fluid F-2-isoprostanes are elevated in Huntington's disease SO NEUROLOGY LA English DT Article C1 Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Ctr Mol Neurosci, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA USA. RP Montine, TJ (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, C3321-A Med Ctr N, Nashville, TN 37232 USA. EM tom.montine@mcmail.vanderbilt.edu FU NIA NIH HHS [AG12992, AG00774, AG11337] NR 6 TC 70 Z9 73 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 23 PY 1999 VL 52 IS 5 BP 1104 EP 1105 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 182UQ UT WOS:000079516900046 PM 10102447 ER PT J AU Simon, JA Hudes, ES AF Simon, JA Hudes, ES TI Relation of serum ascorbic acid to serum vitamin B-12, serum ferritin, and kidney stones in US adults SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID OXALATE EXCRETION; URINARY OXALATE; IRON; DIETARY; ASSAY AB Background: Concern has been raised that high levels of ascorbic acid consumption may lead to potential adverse effects, such as vitamin B-12 deficiency, iron overload, and kidney stones. Objective: To examine the relation of serum ascorbic acid level, which reflects intake, to serum vitamin B-12 level, serum ferritin level, and kidney stones. Methods: We analyzed data collected on a random sample of the US population enrolled in the Second National Health and Nutrition Examination Survey, 1976-1980. We analyzed data using linear and logistic regression models. Serum ascorbic acid, serum vitamin B-12, hemoglobin, red blood cell mean corpuscular volume (MCV), and serum ferritin levels were measured using standardized protocols. History of kidney stones was determined by self-report. Results: After multivariate adjustment, serum ascorbic acid level was associated with higher serum vitamin B-12 levels among women in regression models that assumed a linear relationship; each 57-mu mol/L (1.0-mg/dL) increase in serum ascorbic acid level (range, 6-153 mu mol/L [0.1 to 2.7 mg/dL]) was independently associated with a serum vitamin B-12 level increase of 60 pmol/L (81 pg/mL) (P<.001). Among men, serum ascorbic acid level was marginally associated with higher serum vitamin B-12 levels: each 57-mu mol/L (1.0-mg/dL) increase in serum ascorbic acid level was associated with a serum vitamin Bit level increase of 27 pmol/L (36 pg/mL) (P =.10). In addition, serum ascorbic acid level was not associated with correlates of vitamin Bit deficiency, such as higher MCV levels, macrocytosis (MCV >100), or lower hemoglobin concentrations. Serum ascorbic acid level was not independently associated with serum ferritin levels. However, among women only, serum ascorbic acid levels were associated in a nonlinear fashion with prevalence of elevated serum ferritin levels (P =.02). We found no association between serum ascorbic acid level and prevalence of kidney stones in women or men (both P>.05). Conclusions: Serum ascorbic acid levels were not associated with decreased serum vitamin B-12 levels (or indicators of vitamin B-12 deficiency), prevalence of kidney stones, serum ferritin levels, or-among men-prevalence of elevated serum ferritin levels. Serum ascorbic acid levels were associated with prevalence of elevated serum ferritin levels among women. Although the clinical relevance of these findings is uncertain, it seems prudent to suggest that women with a genetic susceptibility to iron overload should consider moderating their intake of ascorbic acid. C1 San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect 111A1, Med Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Simon, JA (reprint author), San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect 111A1, Med Serv, 4150 Clement St, San Francisco, CA 94121 USA. EM jasimon@itsa.ucsf.edu FU NHLBI NIH HHS [HL53479] NR 41 TC 10 Z9 10 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 22 PY 1999 VL 159 IS 6 BP 619 EP 624 DI 10.1001/archinte.159.6.619 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 177WN UT WOS:000079234200013 PM 10090119 ER PT J AU Zhang, NH Houser, CR AF Zhang, NH Houser, CR TI Ultrastructural localization of dynorphin in the dentate gyrus in human temporal lobe epilepsy: A study of reorganized mossy fiber synapses SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE axonal sprouting; dense core vesicles; electron microscopy; hippocampus; perforated synapses; plasticity ID LONG-TERM POTENTIATION; SEGMENTED POSTSYNAPTIC DENSITIES; CENTRAL NERVOUS-SYSTEM; CA3 PYRAMIDAL NEURONS; KAINATE-TREATED RATS; SYNAPTIC REORGANIZATION; HIPPOCAMPAL-FORMATION; GRANULE CELLS; AXOSPINOUS SYNAPSES; SUBSTANTIA-NIGRA AB Substantial reorganization of mossy fibers from granule cells of the dentate gyrus occurs in a high percentage of humans with medically intractable temporal lobe epilepsy. To identify these fibers and determine their ultrastructural features in human surgical specimens, we used preembedding immunoperoxidase labeling of dynorphin A, an opioid peptide that is abundant in normal mossy fibers. In electron microscopic preparations, dynorphin A immunoreactivity was highly associated with dense core vesicles and was localized predominantly in axon terminals in the inner molecular layer of the dentate gyrus, although some dynorphin-labeled dense core vesicles were also observed in dendritic shafts and spines. The labeled terminal profiles were numerous, and, whereas they varied greatly in size, many were relatively large (2.3 mu M in mean major diameter). The terminals contained high concentrations of clear round vesicles and numerous mitochondrial profiles, formed distinct asymmetric synapses, often had irregular shapes, and, thus, exhibited many features of normal mossy fiber terminals. The dynorphin-labeled terminals formed synaptic contacts primarily with dendritic spines, and some of these spines were embedded in large labeled terminals, suggesting that they were complex spines. The labeled terminals frequently formed multiple synaptic contacts with their postsynaptic elements, and perforated postsynaptic densities, with and without spinules, were present at some synapses. These findings suggest that the reorganized mossy fiber terminals in humans with temporal lobe epilepsy form abundant functional synapses in the inner molecular layer of the dentate gyrus, and many of these contacts have ultrastructural features that could be associated with highly efficacious synapses. (C) 1999 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Dept Neurobiol, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Comprehens Epilepsy Program, Neurol & Res Serv, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, Dept Neurobiol, Sch Med, 73-235 CHS, Los Angeles, CA 90095 USA. EM houser@mednet.ucla.edu NR 102 TC 57 Z9 60 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 22 PY 1999 VL 405 IS 4 BP 472 EP 490 PG 19 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 170UX UT WOS:000078826400003 PM 10098940 ER PT J AU Cook, IA Leuchter, AF Witte, E Abrams, M Uijtdehaage, SHJ Stubbeman, W Rosenberg-Thompson, S Anderson-Hanley, C AF Cook, IA Leuchter, AF Witte, E Abrams, M Uijtdehaage, SHJ Stubbeman, W Rosenberg-Thompson, S Anderson-Hanley, C TI Neurophysiologic predictors of treatment response to fluoxetine in major depression SO PSYCHIATRY RESEARCH LA English DT Article DE treatment outcomes; cordance; neurophysiology; electroencephalography; QEEG ID ANTIDEPRESSANT RESPONSE; ENDOGENOUS-DEPRESSION; DRUG-RESPONSE; EEG; DISORDER; PHARMACOTHERAPY; AMITRIPTYLINE; OUTPATIENTS; NONRESPONSE; IMIPRAMINE AB Treatment with antidepressants is marked by heterogeneity of response; predicting individual response to any given agent remains problematic. Neuroimaging studies suggest that response is accompanied by physiologic changes in cerebral energy utilization, but have not provided useful markers at pretreatment baseline. Using quantitative EEG (QEEG) techniques, we investigated pretreatment neurophysiologic features to identify responders and non-responders to fluoxetine. In a double-masked study, 24 adult subjects with current major depression of the unipolar type were studied over 8 weeks while receiving fluoxetine (20 mg QD) or placebo. Neurophysiology was assessed with QEEG cordance, a measure reflecting cerebral energy utilization. Response was determined with rating scales and clinical interview. Subjects were divided into discordant and concordant groups based upon the number of electrodes exhibiting discordance. The concordant group had a more robust response than the discordant group, judged by lower final Hamilton Depression (HAM-D) mean score (8.0 +/- 7.5 vs. 19.6 +/- 4.7, P = 0.01) and final Beck Depression Inventory (BDI) mean score (14.0 +/- 9.4 vs. 27.8 +/- 3.7, P = 0.015), and by faster reduction in symptoms (HAM-D: 14.0 +/- 5.0 vs. 23.8 +/- 4.1, P = 0.004 at 1 week). Groups did not differ on pretreatment clinical or historical features. Response to placebo was not predicted by this physiologic measure. We conclude that cordance distinguishes depressed adults who will respond to treatment with fluoxetine from those who will not. This measure detects a propensity to respond to fluoxetine and may indicate a more general responsiveness to antidepressants. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Quantitat EEG Lab, Neuropsychiat Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Cook, IA (reprint author), Univ Calif Los Angeles, Sch Med, Quantitat EEG Lab, Neuropsychiat Inst, 760 Westwood Plaza, Los Angeles, CA 90024 USA. OI Uijtdehaage, Sebastian/0000-0001-8598-4683 FU NIMH NIH HHS [KO2-MH01165, KO8-MH01483, R01-MH40705] NR 39 TC 44 Z9 44 U1 0 U2 4 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 MAR 22 PY 1999 VL 85 IS 3 BP 263 EP 273 DI 10.1016/S0165-1781(99)00010-4 PG 11 WC Psychiatry SC Psychiatry GA 195EN UT WOS:000080236300004 PM 10333379 ER PT J AU Kushak, R Drapeau, C van Cott, E Winter, H AF Kushak, R Drapeau, C van Cott, E Winter, H TI Blue-green alga aphanizomenon flos-aquae as a source of dietary polyunsaturated fatty acids and a hypocholesterolemic agent. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Cell Tech, Klamath Falls, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 1999 VL 217 MA 045-AGFD BP U37 EP U37 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148100045 ER PT J AU Lenf, A Kang, JX Xiao, YF Billman, GE Voskuyl, RA AF Lenf, A Kang, JX Xiao, YF Billman, GE Voskuyl, RA TI Electrophysiologic and functional effects of polyunsaturated fatty acids on excitable tissues: Heart and brain. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Ohio State Univ, Dept Physiol, Columbus, OH 45210 USA. Leiden Univ, Med Ctr, Dept Physiol, Leiden, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 21 PY 1999 VL 217 MA 003-AGFD BP U25 EP U25 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 176JN UT WOS:000079148100004 ER PT J AU Liska, V Khimani, AH Hofmann-Lehmann, R Fink, AN Vlasak, J Ruprecht, RM AF Liska, V Khimani, AH Hofmann-Lehmann, R Fink, AN Vlasak, J Ruprecht, RM TI Viremia and AIDS in rhesus macaques after intramuscular inoculation of plasmid DNA encoding full-length SIVmac239 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; MUCOSAL INFECTION; MOLECULAR CLONE; INVIVO; SHEEP; SIV AB We have succeeded in stably maintaining the entire genome of SIVmac239 as a plasmid clone. Supercoiled proviral plasmid DNA was inoculated intramuscularly into two adult rhesus macaques and into a neonate. All three animals became viremic and seroconverted. Viral kinetics mere followed prospectively by quantitative competitive reverse transcriptase polymerase chain reaction (QC-RT-PCR), measurement of proviral DNA load in peripheral blood mononuclear cells (PBMCs) by PCR, and virus isolation by cocultivation. The infant developed high virus loads and succumbed to AIDS and SIV-associated nephropathy at 10 weeks postinoculation. Both adults are still living but have progressed to AIDS; one adult has also developed severe thrombocytopenia. We conclude that infection through intramuscular inoculation of cloned plasmid DNA encoding the entire proviral genome is reproducible and will provide a useful tool for studying viral pathogenesis. C1 Dana Farber Canc Inst, Lab Viral Pathogenesis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NENTM Life Sci, Res & Dev, Boston, MA 02118 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Lab Viral Pathogenesis, 44 Binney St, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu RI Hofmann-Lehmann, Regina/C-6528-2009 FU NIAID NIH HHS [R01 AI32330] NR 20 TC 24 Z9 24 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR 20 PY 1999 VL 15 IS 5 BP 445 EP 450 DI 10.1089/088922299311196 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 178MH UT WOS:000079269400006 PM 10195754 ER PT J AU Nguyen, JT Wu, R Clouse, ME Hlatky, L Terwilliger, EF AF Nguyen, JT Wu, R Clouse, ME Hlatky, L Terwilliger, EF TI Adeno-associated virus-mediated delivery of anti-angiogenic factors as an antitumor strategy SO HUMAN GENE THERAPY LA English DT Meeting Abstract ID INHIBITOR; GROWTH C1 Beth Israel Deaconess Med Ctr, Dept Radiol Sci, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 20 PY 1999 VL 10 IS 5 BP 839 EP 839 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 181EY UT WOS:000079429200026 ER PT J AU Ganly, I Kirn, D Posner, M Vokes, E Nemunaitis, J Kaye, S AF Ganly, I Kirn, D Posner, M Vokes, E Nemunaitis, J Kaye, S TI A phase II trial of intratumoural injection with an E1B-deleted adenovirus, Onyx-015, in patients with recurrent refractory head and neck cancer SO HUMAN GENE THERAPY LA English DT Meeting Abstract C1 Beatson Oncol Ctr, Dept Med Oncol, Glasgow, Lanark, Scotland. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Dept Med Oncol, Chicago, IL 60637 USA. Phys Reliance Network, Dallas, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 20 PY 1999 VL 10 IS 5 BP 844 EP 844 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 181EY UT WOS:000079429200036 ER PT J AU Huang, ZQ Philippin, B O'Leary, E Bonventre, JV Kriz, W Witzgall, R AF Huang, ZQ Philippin, B O'Leary, E Bonventre, JV Kriz, W Witzgall, R TI Expression of the transcriptional repressor protein Kid-1 leads to the disintegration of the nucleolus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-I; ZINC-FINGER PROTEINS; DNA-BINDING; FACTOR UBF; MEDIATED REPRESSION; GENE-TRANSCRIPTION; MAMMALIAN-CELLS; NUCLEAR MATRIX; KRUPPEL-TYPE; FACTOR HUBF AB The rat Kid-1 gene codes for a 66-kDa protein with KRAB domains at the NH2 terminus and two Cys(2)His(2)-zinc finger clusters of four and nine zinc fingers at the COOH terminus. It was the first KRAB-zinc finger protein for which a transcriptional repressor activity was demonstrated. Subsequently, the KRAB-A domain was identified as a widespread transcriptional repressor motif, We now present a biochemical and functional analysis of the Kid-1 protein in transfected cells. The full-length Kid-1 protein is targeted to the nucleolus and adheres tightly to as yet undefined nucleolar structures, leading eventually to the disintegration of the nucleolus. The tight adherence and nucleolar distribution can be attributed to the larger zinc finger cluster, whereas the KRAB-A domain is responsible for the nucleolar fragmentation, Upon disintegration of the nucleolus, the nucleolar transcription factor upstream binding factor disappears from the nucleolar fragments, In the absence of Kid-1, the KRIP-1 protein, which represents the natural interacting partner of zinc finger proteins with a KRAB-A domain, is homogeneously distributed in the nucleus, whereas coexpression of Kid-1 leads to a shift of KRIP-1 into the nucleolus. Nucleolar run-ons demonstrate that rDNA transcription is shut off in the nucleolar fragments. Our data demonstrate the functional diversity of the KRAB and zinc finger domains of Kid-1 and provide new functional insights into the regulation of the nucleolar structure. C1 Univ Heidelberg, Inst Anat & Cell Biol 1, D-69120 Heidelberg, Germany. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Witzgall, R (reprint author), Univ Heidelberg, Inst Anat & Cell Biol 1, Neuenheimer Feld 307, D-69120 Heidelberg, Germany. FU NIDDK NIH HHS [DK39773] NR 64 TC 18 Z9 18 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 19 PY 1999 VL 274 IS 12 BP 7640 EP 7648 DI 10.1074/jbc.274.12.7640 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 178LU UT WOS:000079268100010 PM 10075651 ER PT J AU Beggah, AT Beguin, P Bamberg, K Sachs, G Geering, K AF Beggah, AT Beguin, P Bamberg, K Sachs, G Geering, K TI beta-subunit assembly is essential for the correct packing and the stable membrane insertion of the H,K-ATPase alpha-subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IN-VITRO TRANSLATION; NA,K-ATPASE; TOPOLOGY; TRANSMEMBRANE; TRANSLOCATION; NA,K-PUMPS; SYSTEM AB The alpha-subunits of H,K-ATPase (HKA alpha) and Na,K-ATPase require a beta-subunit for maturation. We investigated the role of the beta-subunit in the membrane insertion and stability of the HKA alpha expressed in Xenopus oocytes, Individual membrane segments M1, M2, M3, M4, and M9 linked to a glycosylation reporter act as signal anchor (SA) motifs, and M10 acts as a partial stop transfer motif. In combined HKA alpha constructs, M2 acts as an efficient stop transfer sequence, and M3 acts as a SA sequence. However, M5 and M9 have only partial SA function, and M7 has no SA function. Consistent with the membrane insertion properties of segments in combined a constructs, M1-3 alpha-proteins are resistant to cellular degradation, and M1-5 up to M1-10 alpha-proteins are not resistant to cellular degradation. However, co-expression with beta-subunits increases the membrane insertion of M9 in a M1-9 alpha-protein and completely protects M1-10 alpha-proteins against cellular degradation. Our results indicate that HKA alpha N-terminal (M1-M4) membrane insertion and stabilization are mediated by intrinsic molecular characteristics; however, the C-terminal (M5-M10) membrane insertion and thus the stabilization of the entire alpha-subunit depend on intramolecular and intermolecular beta-subunit interactions that are similar but not identical to data obtained for the Na,K-ATPase alpha-subunit. C1 Univ Lausanne, Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland. Astra Hassle AB, S-43183 Molndal, Sweden. W Los Angeles Wadsworth Vet Adm Med Ctr, Los Angeles, CA 90073 USA. RP Geering, K (reprint author), Univ Lausanne, Inst Pharmacol & Toxicol, Rue Bugnon 27, CH-1005 Lausanne, Switzerland. NR 26 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 19 PY 1999 VL 274 IS 12 BP 8217 EP 8223 DI 10.1074/jbc.274.12.8217 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 178LU UT WOS:000079268100085 PM 10075726 ER PT J AU Duan, ZF Feller, AJ Toh, HC Makastorsis, T Seiden, MV AF Duan, ZF Feller, AJ Toh, HC Makastorsis, T Seiden, MV TI TRAG-3, a novel gene, isolated from a taxol-resistant ovarian carcinoma cell line SO GENE LA English DT Article DE cancer; differential display; drug resistance; genetics; mRNA expression ID DIFFERENTIAL DISPLAY; DRUG-RESISTANCE; PACLITAXEL; CANCER AB The mechanisms responsible for the development of the taxol resistance phenotype are unclear, and are likely explained by multiple mechanisms. To understand the molecular changes associated with drug resistance more fully, a taxol-resistant subline, derived from the human ovarian cancer cell line SKOV-3, was established through selection by culture in incrementally increasing taxol concentrations. Comparison of SKOV-3 to SKOV-3,, by differential display identifies a new gene, TRAG-3 ((T) under bar axol (R) under bar esistance (A) under bar ssociated (G) under bar ene-3). In comparison to the parental line, SKOV-3, TRAG-3 mRNA is overexpressed in the taxol-resistant cell line SKOV-3(TR). The nucleotide sequence of the TRAG-3 cDNA contains an open reading frame of 333 bp that predicts for a protein product of 110 amino acids. A GenBank search identifies a cosmid clone containing a genomic sequence corresponding to that of TRAG-3. DNA and protein analysis reveals that TRAG3 has no homology to any known cDNAs or proteins. Northern analysis demonstrates that TRAG3 is overexpressed in the taxol-resistant breast cancer cell line MDA 435(TR) as well as the doxorubicin-resistant multiple myeloma cell lines 8226/DOX40 and 8226/MDR10V. A survey of normal tissue shows minimal or absent TRAG3 mRNA expression. Screening of a wide variety of cancer cell lines demonstrates TRAG-3 expression in many cell lines derived from different tissue types. In summary, TRAG-3 is a novel gene whose expression is associated with the chemotherapy-resistant and neoplastic phenotype. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 15 TC 61 Z9 68 U1 2 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 18 PY 1999 VL 229 IS 1-2 BP 75 EP 81 DI 10.1016/S0378-1119(99)00042-6 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 179XP UT WOS:000079355600009 PM 10095106 ER PT J AU Hogan, PG Rao, A AF Hogan, PG Rao, A TI Transcriptional regulation - Modification by nuclear export? SO NATURE LA English DT Editorial Material ID FACTOR NFAT1; NF-ATC; CALCINEURIN; MECHANISMS; SIGNALS; CELLS C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hogan, PG (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 14 TC 17 Z9 17 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 18 PY 1999 VL 398 IS 6724 BP 200 EP 201 DI 10.1038/18327 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177UA UT WOS:000079228400030 PM 10094042 ER PT J AU Kulke, MH Mayer, RJ AF Kulke, MH Mayer, RJ TI Carcinoid tumors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID METASTATIC NEUROENDOCRINE TUMORS; MULTIPLE ENDOCRINE NEOPLASIA; ZOLLINGER-ELLISON SYNDROME; HEPATIC ARTERIAL CHEMOEMBOLIZATION; ISLET-CELL CARCINOMAS; GASTRIC CARCINOIDS; HEART-DISEASE; LIVER-TRANSPLANTATION; SOMATOSTATIN ANALOG; PERNICIOUS-ANEMIA C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5T32CA09172] NR 135 TC 459 Z9 486 U1 3 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 18 PY 1999 VL 340 IS 11 BP 858 EP 868 DI 10.1056/NEJM199903183401107 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 176ZW UT WOS:000079183200007 PM 10080850 ER PT J AU Farmer, PE Rao, P Basgoz, N Murtagh, MJ AF Farmer, PE Rao, P Basgoz, N Murtagh, MJ TI A 28-year-old man with Gram-negative sepsis of uncertain cause - Enteric fever due to Salmonella typhi SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID VIRULENCE C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Clin Bon Sauveur, Cange, Haiti. Harvard Med Sch, Program Infect Dis & Social Change, Boston, MA USA. RP Farmer, PE (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. NR 31 TC 5 Z9 5 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 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 18 PY 1999 VL 340 IS 11 BP 869 EP 876 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 176ZW UT WOS:000079183200008 ER PT J AU McGee, S Abernethy, WB Simel, DL AF McGee, S Abernethy, WB Simel, DL TI Is this patient hypovolemic? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ORTHOSTATIC VITAL SIGNS; ACUTE BLOOD-LOSS; HEAD-UP TILT; POSTURAL HYPOTENSION; ELDERLY PATIENTS; HEMODYNAMIC-RESPONSE; PRESSURE CHANGES; CLINICAL SIGNS; OLD-AGE; DEHYDRATION AB Objective To review, systematically, the physical diagnosis of hypovolemia in adults. Methods We searched MEDLINE (January 1966-November 1997), personal files, and bibliographies of textbooks on physical diagnosis and identified 10 studies investigating postural vital signs or the capillary refill time of healthy volunteers, some of whom underwent phlebotomy of up to 1150 mL of blood, and 4 studies of patients presenting to emergency departments with suspected hypovolemia, usually due to vomiting, diarrhea, or decreased oral intake. Results When clinicians evaluate adults with suspected blood loss, the most helpful physical findings are either severe postural dizziness (preventing measurement of upright vital signs) or a postural pulse increment of 30 beats/min or more. The presence of either finding has a sensitivity for moderate blood loss of only 22% (95% confidence interval [CI], 6%-48%) but a much greater sensitivity for large blood loss of 97% (95% CI, 91%-100%); the corresponding specificity is 98% (95% CI, 97%-99%). Supine hypotension and tachycardia are frequently absent, even after up to 1150 mt of blood loss (sensitivity, 33%; 95% CI, 21%-47%, for supine hypotension). The finding of mild postural dizziness has no proven value. In patients with vomiting, diarrhea, or decreased oral intake, the presence of a dry axilla supports the diagnosis of hypovolemia (positive likelihood ratio, 2.8; 95% CI, 1.4-5.4), and moist mucous membranes and a tongue without furrows argue against it (negative likelihood ratio, 0.3; 95% CI, 0.1-0.6 for both findings). In adults, the capillary refill time and poor skin turgor have no proven diagnostic value. Conclusions A large postural pulse change (greater than or equal to 30 beats/min) or severe postural dizziness is required to clinically diagnose hypovolemia due to blood loss, although these findings are often absent after moderate amounts of blood loss. In patients with vomiting, diarrhea, or decreased oral intake, few findings have proven utility, and clinicians should measure serum electrolytes, serum blood urea nitrogen, and creatinine levels when diagnostic certainty is required. C1 Univ Washington, Seattle Puget Sound VA Hlth Care Syst 111, Dept Med, Seattle, WA 98108 USA. Massachusetts Gen Hosp, Dept Cardiovasc Med, Boston, MA 02114 USA. Duke Univ, Dept Med Ambulatory Care, Durham, NC USA. Durham Vet Affairs Med Ctr, Durham, NC USA. RP McGee, S (reprint author), Univ Washington, Seattle Puget Sound VA Hlth Care Syst 111, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 81 TC 237 Z9 239 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 17 PY 1999 VL 281 IS 11 BP 1022 EP 1029 DI 10.1001/jama.281.11.1022 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 175EE UT WOS:000079079400030 PM 10086438 ER PT J AU Mukherjee, P Sotnikov, AV Mangian, HJ Zhou, JR Visek, WJ Clinton, SK AF Mukherjee, P Sotnikov, AV Mangian, HJ Zhou, JR Visek, WJ Clinton, SK TI Energy intake and prostate tumor growth, angiogenesis, and vascular endothelial growth factor expression SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PROGRAMMED CELL-DEATH; FACTOR VEGF EXPRESSION; RAT VENTRAL PROSTATE; FACTOR-I; ANDROGEN ABLATION; UNITED-STATES; CANCER RISK; BODY-WEIGHT; NUDE-MICE; INSULIN AB Background: A sedentary lifestyle coupled with excessive energy intake is speculated to be a factor associated with increased incidence of prostate cancer. We have investigated the effects of energy intake on prostate tumor growth in experimental animals, Methods: Two transplantable prostate tumor models, i.e., the androgen-dependent Dunning R3327-H adenocarcinoma in rats and the androgen-sensitive LNCaP human carcinoma in severe combined immunodeficient mice, were studied. R3327-H tumor growth and relevant tumor biomarkers (proliferation index, apoptosis [programmed cell death], microvessel density, and vascular endothelial growth factor [VEGF] expression) were compared in ad libitum fed control rats, ad libitum fed castrated rats, and groups restricted in energy intake by 20% or 40%. A second set of experiments involving both tumor models examined tumor growth in ad libitum fed rats or in animals whose energy intake was restricted by 30% using three different methods, i.e., total diet restriction, carbohydrate restriction, or lipid restriction. All P values are two-sided, Results: R3327-H tumors were smaller in energy-restricted or castrated rats than in control rats (P<.001). Tumors from energy-restricted rats exhibited changes in tumor architecture characterized by increased stroma and more homogeneous and smaller glands, In castrated rats, the tumor proliferation index was reduced (P<.0001), whereas apoptosis was increased in both energy-restricted (P<.001) and castrated (P<.001) rats, Tumor microvessel density and VEGF expression mere reduced by energy restriction and castration (P<.003 versus control), Restriction of energy intake by reduction of carbohydrate intake, lipid intake, or total diet produced a similar inhibition of growth of R3327-H or LNCaP tumors. These effects were associated with reduced circulating insulin-like growth factor-I. Conclusions: Our observations are consistent with the hypothesis that energy restriction reduces prostate tumor growth by inhibiting tumor angiogenesis, Furthermore, dietary fat concentration does not influence prostate tumor growth when energy intake is reduced. C1 Ohio State Univ, Arthur G James Canc Hosp & Res Inst, Columbus, OH 43210 USA. Univ Illinois, Coll Med, Div Nutr Sci, Urbana, IL 61801 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. RP Clinton, SK (reprint author), Ohio State Univ, Arthur G James Canc Hosp & Res Inst, B402 Starling Loving Hall,320 W 10th St, Columbus, OH 43210 USA. FU NCI NIH HHS [F32CA71161, K07CA01680, R01CA72482] NR 64 TC 162 Z9 167 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 17 PY 1999 VL 91 IS 6 BP 512 EP 523 DI 10.1093/jnci/91.6.512 PG 12 WC Oncology SC Oncology GA 177WY UT WOS:000079235100010 PM 10088621 ER PT J AU Syngal, S Coakley, EH Willett, WC Byers, T Williamson, DF Colditz, GA AF Syngal, S Coakley, EH Willett, WC Byers, T Williamson, DF Colditz, GA TI Long-term weight patterns and risk for cholecystectomy in women SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE cholelithiasis; weight loss; weight gain; cholecystectomy ID GASTRIC BYPASS-SURGERY; GALLSTONE DISEASE; GALLBLADDER-DISEASE; SYMPTOMATIC GALLSTONES; MORBID-OBESITY; URSODEOXYCHOLIC ACID; PHYSICAL-ACTIVITY; RELATIVE WEIGHT; UNITED-STATES; GALL-STONES AB Background: Obesity and rapid weight loss in obese persons are known risk factors for gallstones. However, the effect of intentional, long-term, moderate weight changes on the risk for gallstones is unclear. Objective: To study long-term weight patterns in a cohort of women and to examine the relation between weight pattern and risk for cholecystectomy. Design: Prospective cohort study. Setting: 11 U.S. states. Participants: 47 153 female registered nurses who did not undergo cholecystectomy before 1988. Measurements: Cholecystectomy between 1988 and 1994 (ascertained by patient self-report). Results: During the exposure period (1972 to 1988), there was evidence of substantial Variation in weight due to intentional weight loss during adulthood. Among cohort patients, 54.9% reported weight cycling with at least one episode of intentional weight loss associated with regain. Of the total cohort, 20.1% were light cyclers (5 to 9 Ib of weight loss and gain), 18.8% were moderate cyclers(10 to 19 lb of weight loss and gain), and 16.0% were severe cyclers (greater than or equal to 20 lb of weight loss and gain). Net weight gain without cycling occurred in 29.3% of women; net weight loss without cycling was the least common pattern (4.6%). Only 11.1% of the cohort maintained weight within 5 lb over the 16-year period. In the study, 1751 women had undergone cholecystectomy between 1988 and 1994. Compared with weight maintainers, the relative risk for cholecystectomy (adjusted for body mass index, age, alcohol intake, fat intake, and smoking) was 1.20 (95% CI, 0.96 to 1.50) among light cyclers, 1.31 among moderate cyclers (CI, 1.05 to 1.64), and 1.68 among severe cyclers (CI, 1.34 to 2.10). Conclusion: Weight cycling was highly prevalent in this large cohort of middle-aged women. The risk for cholecystectomy associated with weight cycling was substantial, independent of attained relative body weight. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Div Diabet Translat K10, Atlanta, GA 30341 USA. Univ Colorado, Sch Med, Dept Prevent Med & Biometr, Denver, CO 80262 USA. RP Colditz, GA (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [5R25CA57711, CA 40356]; NIDDK NIH HHS [DK 46200] NR 44 TC 49 Z9 52 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 16 PY 1999 VL 130 IS 6 BP 471 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 176RL UT WOS:000079165500002 PM 10075614 ER PT J AU Lewis, JD Asch, DA AF Lewis, JD Asch, DA TI Barriers to office-based screening sigmoidoscopy: Does reimbursement cover costs? SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID COLORECTAL-CANCER; RECOMMENDATIONS; MORTALITY AB Screening with flexible sigmoidoscopy may reduce mortality rates from colorectal cancer. Primary care physicians are able to provide this screening procedure, but many have been reluctant to do so, partly because of the impression that reimbursement rates are inadequate to cover physician costs. This study examines the cost of performing flexible sigmoidoscopy in a primary care practice and compares this cost with the new Medicare reimbursement rate for flexible sigmoidoscopy. Fixed and variable costs associated with the performance of office-based flexible sigmoidoscopy were derived from the published literature. The principal assumption in the analyses is that the time required to perform flexible sigmoidoscopy represents an opportunity cost because the physician could use that time to see additional patients during routine office hours. Sensitivity analyses were done across a range of estimates for the cost variables. When Medicare reimbursement rates were used, the physician's total cost for flexible sigmoidoscopy without biopsy was $86.86, which is similar to the Medicare reimbursement rate for screening flexible sigmoidoscopy (code 45330, $87.84). The calculations were most sensitive to estimates of equipment cost, procedure time, number of procedures performed per year, additional malpractice coverage, and revenue generated per hour of outpatient care. The estimated cost per procedure in a screening prog ram that includes the ability to perform biopsy is $152.93, which exceeds Medicare reimbursement rates across the range of all variables included in the sensitivity analyses. Thus, low reimbursement may limit the adoption of screening flexible sigmoidoscopy with or without biopsy in primary care practices. C1 Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Lewis, JD (reprint author), Univ Penn, Ctr Clin Epidemiol & Biostat, 8th Floor,Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM jlewis@cceb.med.upenn.edu FU NIDDK NIH HHS [1-T32-DK07740-0] NR 21 TC 62 Z9 62 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 16 PY 1999 VL 130 IS 6 BP 525 EP 530 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 176RL UT WOS:000079165500009 PM 10075621 ER PT J AU Guntermann, C Murphy, BJ Zheng, R Qureshi, A Eagles, PA Nye, KE AF Guntermann, C Murphy, BJ Zheng, R Qureshi, A Eagles, PA Nye, KE TI Human immunodeficiency virus-1 infection requires pertussis toxin sensitive G-protein-coupled signalling and mediates cAMP downregulation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TYROSINE KINASE P56LCK; T-CELLS; CHEMOKINE RECEPTORS; HIV-1; CD4; GP120; LYMPHOCYTES; ACTIVATION; GLYCOPROTEIN; INHIBITION AB The human immunodeficiency virus-1 (HIV-1) utilises CD4 and certain beta-chemokine receptors, mainly CCR-5 and CXCR4, for attachment and virus entry into T-lymphocytes and monocytes/maerophages. CD4 and beta-chemokine receptors participate in intracellular signalling via protein tyrosine kinases and G-protein-coupled signalling, The factors which influence HIV-1 replication and the intracellular signalling mechanisms elicited by the virus are not well understood. In this study, it was demonstrated that exposure of peripheral blood lymphocytes (PBLs) to a T-cell tropic strain of HIV-1 evokes signal(s) which results in downregulation of intracellular cAMP. In addition, preincubation of PBLs with the G(i)-protein inhibitor Pertussis toxin mediated a significant inhibition of HIV-1 replication. These data strongly suggest that HIV-1 employs CD4 receptors and Gi-coupled proteins for entry into target cells and that productive HIV-1 infection is dependent on an active signalling event. (C) 1999 Academic Press. C1 St Bartholomews & Royal London Sch Med & Dent, Dept Immunol, London EC1A 7BE, England. Univ London Kings Coll, Randall Inst, Dept Mol Biol & Biophys, London, England. RP Guntermann, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM christine_guntermann@macmailgw.dfci.harvard.edu NR 23 TC 31 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 16 PY 1999 VL 256 IS 2 BP 429 EP 435 DI 10.1006/bbrc.1999.0333 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 177YG UT WOS:000079238200034 PM 10079202 ER PT J AU Lee-Huang, S Huang, PL Sun, YT Huang, PL Kung, HF Blithe, DL Chen, HC AF Lee-Huang, S Huang, PL Sun, YT Huang, PL Kung, HF Blithe, DL Chen, HC TI Lysozyme and RNases as anti-HIV components in beta-core preparations of human chorionic gonadotropin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AIDS; muramidase; urinary proteins; antiviral agents ID SARCOMA CELL-LINE; KAPOSIS-SARCOMA; RIBONUCLEASE; HORMONE; FRAGMENT; GROWTH; URINE; MICE AB Human chorionic gonadotropin (hCG) preparations contain activity against HIT: type 1 (HIV-1). However, there has been controversy about whether some biological activities of hCG beta-subunit (hCG beta) preparations are caused by the beta-subunit itself or other proteins present in the preparations, We report here the purification, characterization, and identification of three enzymes with anti-HIV activity present in the beta-core fraction of hCG beta prepared from the urine of pregnant women. The N-terminal amino acid sequence of one protein is identical to human urinary lysozyme C, and those of the other two are identical to human RNase A and urinary RNase U. We thus refer to these proteins as AVL (antiviral lysozyme) and AVR (antiviral RNases). In addition to HIV-1 inhibition, AVL is capable of lysing Micrococcus lysodeikticus. AVR digests a variety of RNA substrates, including RNA from HIV-1-infected cells. We also find that lysozyme from chicken egg white, human milk and human neutrophils and RNase A from bovine pancreas possess activity against HIV-I. These findings may offer additional strategies for the treatment of HIV-1 infection. C1 NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Community Hlth Plan, Boston, MA 02114 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Frederick, MD 21701 USA. NICHHD, Contracept & Reprod Hlth Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Chen, HC (reprint author), NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. FU NIAID NIH HHS [AI-31343] NR 21 TC 215 Z9 226 U1 0 U2 9 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 MAR 16 PY 1999 VL 96 IS 6 BP 2678 EP 2681 DI 10.1073/pnas.96.6.2678 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177RH UT WOS:000079224500024 PM 10077570 ER PT J AU Saoncella, S Echtermeyer, F Denhez, F Nowlen, JK Mosher, DF Robinson, SD Hynes, RO Goetinck, PF AF Saoncella, S Echtermeyer, F Denhez, F Nowlen, JK Mosher, DF Robinson, SD Hynes, RO Goetinck, PF TI Syndecan-4 signals cooperatively with integrins in a Rho-dependent manner in the assembly of focal adhesions and actin stress fibers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE-C; GENOMIC ORGANIZATION; MOLECULAR-CLONING; CELL-ADHESION; GENE; TRANSDUCTION; CYTOSKELETAL; PROTEOGLYCAN; FIBRONECTIN AB The assembly of focal adhesions and actin stress fibers by cells plated on fibronectin depends on adhesion-mediated signals involving both integrins and cell-surface heparan sulfate proteoglycans. These two cell-surface receptors interact with different domains of fibronectin, To attempt to identify the heparan sulfate proteoglycans involved, we used fibronectin-null (FN-/-) mouse fibroblasts to eliminate the contribution of endogenous fibronectin during the analysis. FN-/- fibroblasts plated on the cell-binding domain of fibronectin or on antibodies directed against mouse beta 1 integrin chains attach but fail to spread and do not form focal adhesions or actin stress fibers. When such cells are treated with antibodies directed against the ectodomain of mouse syndecan-4, they spread fully and assemble focal adhesions and actin stress fibers indistinguishable from those seen in cells plated on intact fibronectin, These results identify syndecan-4 as a heparan sulfate proteoglycan involved in the assembly process. The antibody-stimulated assembly of focal adhesions and actin stress fibers in cells plated on the cell-binding domain of fibronectin can be blocked with C3 exotransferase, an inhibitor of the small GTP-binding protein Rho, Treatment of cells with lysophosphatidic acid, which activates Rho, results in full spreading and assembly of focal adhesions and actin stress fibers in fibroblasts plated on the cell-binding domain of fibronectin. We conclude that syndecan-4 and integrins can act cooperatively in generating signals for cell spreading and for the assembly of focal adhesions and actin stress fibers. We conclude further that these joint signals are regulated in a Rho-dependent manner. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Cambridge, MA 02139 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. MIT, Dept Biol, Ctr Canc Res, Cambridge, MA 02139 USA. RP Goetinck, PF (reprint author), Cutaneous Biol Res Ctr, MGH E,Bldg 149,13th St, Cambridge, MA 02139 USA. EM pgoetinck@cbrc.mgh.harvard.edu FU NHLBI NIH HHS [HL21644, P0-HL41484, R01 HL021644]; NICHD NIH HHS [HD-22016] NR 32 TC 288 Z9 289 U1 0 U2 9 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 MAR 16 PY 1999 VL 96 IS 6 BP 2805 EP 2810 DI 10.1073/pnas.96.6.2805 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177RH UT WOS:000079224500046 PM 10077592 ER PT J AU Martelli, F Livingston, DM AF Martelli, F Livingston, DM TI Regulation of endogenous E2F1 stability by the retinoblastoma family proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID UBIQUITIN-PROTEASOME PATHWAY; DIHYDROFOLATE-REDUCTASE PROMOTER; TRANSCRIPTION FACTOR E2F-1; CELL-CYCLE PROGRESSION; S-PHASE ENTRY; GROWTH-REGULATION; MAMMALIAN-CELLS; BINDING PROTEIN; MOUSE E2F1; LARGE-T AB Certain E2F transcription factor species play a pivotal role in regulating cell-cycle progression. The activity of E2F1, a protein with neoplastic transforming activity when unregulated, is tightly controlled at the transcriptional level during G(0) exit, In addition, during this interval, the stability of endogenous E2F1 protein increased markedly. E2F1 stability also was dynamically regulated during myogenic differentiation and in response to gamma irradiation, One or more retinoblastoma family proteins likely participate in the stability process, because simian virus 40 T antigen disrupted E2F1 stability regulation during G(1) exit in a manner dependent on its ability to bind to pocket proteins, Thus, endogenous E2F1 function is regulated by both transcriptional and posttranscriptional control mechanisms. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Martelli, Fabio/0000-0002-8624-7738 NR 57 TC 31 Z9 31 U1 0 U2 2 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 MAR 16 PY 1999 VL 96 IS 6 BP 2858 EP 2863 DI 10.1073/pnas.96.6.2858 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177RH UT WOS:000079224500055 PM 10077601 ER PT J AU Tamayo, P Slonim, D Mesirov, J Zhu, Q Kitareewan, S Dmitrovsky, E Lander, ES Golub, TR AF Tamayo, P Slonim, D Mesirov, J Zhu, Q Kitareewan, S Dmitrovsky, E Lander, ES Golub, TR TI Interpreting patterns of gene expression with self-organizing maps: Methods and application to hematopoietic differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; RETINOIC ACID; RAR-ALPHA; PROTEIN; PML; TRANSLOCATION; T(15-17); CLUSTER; ENCODES AB Array technologies have made it straightforward to monitor simultaneously the expression pattern of thousands of genes. The challenge now is to interpret such massive data sets. The first step is to extract the fundamental patterns of gene expression inherent in the data. This paper describes the application of self-organizing maps, a type of mathematical cluster analysis that is particularly well suited for recognizing and classifying features in complex, multidimensional data. The method has been implemented in a publicly available computer package, GENECLUSTER, that performs the analytical calculations and provides easy data visualization. To illustrate the value of such analysis, the approach is applied to hematopoietic differentiation in four well studied models (HL-60, U937, Jurkat, and NB4 cells). Expression patterns of some 6,000 human genes were assayed, and an online database was created. GENECLUSTER was used to organize the genes into biologically relevant clusters that suggest novel hypotheses about hematopoietic differentiation-for example, highlighting certain genes and pathways involved in "differentiation therapy" used in the treatment of acute promyelocytic leukemia. C1 Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lander, ES (reprint author), MIT, Ctr Genome Res, Bldg 300,1 Kendall Sq, Cambridge, MA 02139 USA. EM lander@genome.wi.mit.edu; golub@genome.wi.mit.edu NR 28 TC 1910 Z9 1991 U1 6 U2 51 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 MAR 16 PY 1999 VL 96 IS 6 BP 2907 EP 2912 DI 10.1073/pnas.96.6.2907 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177RH UT WOS:000079224500064 PM 10077610 ER PT J AU Hagstrom, SA Dryja, TP AF Hagstrom, SA Dryja, TP TI Mitotic recombination map of 13cen-13q14 derived from an investigation of loss of heterozygosity in retinoblastomas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEREDITARY RETINOBLASTOMA; CHROMOSOME 13; GENE; MUTATIONS; MECHANISMS; LOCUS AB Loss of heterozygosity at tumor-suppressor loci is an important oncogenic mechanism first discovered in retinoblastomas. We explored this phenomenon by examining a set of matched retinoblastoma and leukocyte DNA samples from 158 patients informative for DNA polymorphisms. Loss of heterozygosity at the retinoblastoma locus (13q14) was observed in 101 cases, comprising 7 cases with a somatic deletion causing hemizygosity and 94 with homozygosity (iso-disomy). Homozygosity was approximately equally frequent in tumors from male and female patients, among patients with a germ-line vs. somatic initial mutation, and among patients in whom the initial mutation occurred on the maternal vs, paternal allele, A set of 75 tumors exhibiting homozygosity was investigated with markers distributed in the interval 13cen-13q14. Forty-one tumors developed homozygosity at all informative marker loci, suggesting that homozygosity occurred through chromosomal nondisjunction, The remaining cases exhibited mitotic recombination, There was no statistically significant bias in apparent nondisjunction vs. mitotic recombination among male vs, female patients or among patients with germ-line vs. somatic initial mutations. We compared the positions of somatic recombination events in the analyzed interval with a previously reported meiotic recombination map,Although mitotic crossovers occurred throughout the assayed interval, they were more likely to occur proximally than a comparable number of meiotic crossovers. Finally, we observed four triple-crossover cases, suggesting negative interference for mitotic recombination, the opposite of that is usually observed for meiotic recombination. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [F32 EY006915, F32 EY06915, R01 EY008683, R01 EY08683, T32 EY007145, T32 EY07145] NR 21 TC 81 Z9 82 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 MAR 16 PY 1999 VL 96 IS 6 BP 2952 EP 2957 DI 10.1073/pnas.96.6.2952 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177RH UT WOS:000079224500072 PM 10077618 ER PT J AU Casasnovas, JM Pieroni, C Springer, TA AF Casasnovas, JM Pieroni, C Springer, TA TI Lymphocyte function-associated antigen-1 binding residues in intercellular adhesion molecule-2 (ICAM-2) and the integrin binding surface in the ICAM subfamily SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMINO-ACID-RESIDUES; CELL-ADHESION; CRYSTAL-STRUCTURE; LIGAND-BINDING; A-DOMAIN; LFA-1; SUBUNIT; SITE; VCAM-1; RECOGNITION AB The crystal structure of intercellular adhesion molecule-2 (ICAM-2) revealed significant differences in the presentation of the critical acidic residue important for integrin binding between I and non-I-domain integrin ligands, Based on this crystal structure, we mutagenized ICAM-2 to localize the binding site for the integrin lymphocyte function-associated antigen-1 (LFA-I), The integrin binding site runs diagonally across the GFC beta-sheet and includes residues on the CD edge of the beta-sandwich. The site is oblong and runs along a flat ridge on the upper half of domain 1, which is proposed to dock to a groove in the I domain of LFA-1, with the critical Glu-37 residue ligating the Mg2+ in the I domain. Previous mutagenesis of ICAM-1 and ICAM-3, interpreted in light of the recently determined ICAM-1 and ICAM-2 structures, suggests similar binding sites. By contrast, major differences are seen with vascular cell adhesion molecule-1 (VCAM-1), which binds alpha(4) integrins that lack an I domain. The binding site on VCAM-1 includes the lower portion of domain 1 and the upper part of domain 2, whereas the LFA-1 binding site on ICAM is confined to the upper part of domain 1. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 FU NCI NIH HHS [CA31798, R37 CA031798, R01 CA031798] NR 33 TC 26 Z9 26 U1 1 U2 2 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 MAR 16 PY 1999 VL 96 IS 6 BP 3017 EP 3022 DI 10.1073/pnas.96.6.3017 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177RH UT WOS:000079224500083 PM 10077629 ER PT J AU Elisseeff, J Anseth, K Sims, D McIntosh, W Randolph, M Langer, R AF Elisseeff, J Anseth, K Sims, D McIntosh, W Randolph, M Langer, R TI Transdermal photopolymerization for minimally invasive implantation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MODEL; AGENTS AB Photopolymerizations are widely used in medicine to create polymer networks for use in applications such as bone restorations and coatings for artificial implants. These photopolymerizations occur by directly exposing materials to light in "open" environments such as the oral cavity or during invasive procedures such as surgery, We hypothesized that light, which penetrates tissue including shin, could cause a photopolymerization indirectly. Liquid materials then could be injected s.c. and solidified by exposing the exterior surface of the skin to light. To test this hypothesis, the penetration of UVA and visible light through skin was studied, Modeling predicted the feasibility of transdermal polymerization with only 2 min of light exposure required to photopolymerize an implant underneath human shin, To establish the validity of these modeling studies, transdermal photopolimerization first was applied to tissue engineering by using "injectable" cartilage as a model system. Polymer/chondrocyte constructs were injected s,c, and transdermally. photopolymerized. Implants harvested at 2, 4, and 7 weeks demonstrated collagen and proteoglycan production and histology with tissue structure comparable to native neocartilage, To further examine this phenomenon and test the applicability of transdermal photopolymerization for drug release devices, albumin, a model protein, was released for 1 week from photopolymerized hydrogels. With further study, transdermal photpolymerization potentially could be used to create a variety of new, minimally invasive surgical procedures in applications ranging from plastic and orthopedic surgerSr to tissue engineering and drug delivery. C1 Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Univ Colorado, Dept Chem Engn, Boulder, CO 80309 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Langer, R (reprint author), 400 Main St,E25-342, Cambridge, MA 02139 USA. FU NIDCR NIH HHS [1-RO1DE13023-01, R01 DE013023] NR 19 TC 323 Z9 332 U1 1 U2 61 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 MAR 16 PY 1999 VL 96 IS 6 BP 3104 EP 3107 DI 10.1073/pnas.96.6.3104 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177RH UT WOS:000079224500098 PM 10077644 ER PT J AU Netti, PA Hamberg, LM Babich, JW Kierstead, D Graham, W Hunter, GJ Wolf, GL Fischman, A Boucher, Y Jain, RK AF Netti, PA Hamberg, LM Babich, JW Kierstead, D Graham, W Hunter, GJ Wolf, GL Fischman, A Boucher, Y Jain, RK TI Enhancement of fluid filtration across tumor vessels: Implication for delivery of macromolecules SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN ADENOCARCINOMA LS174T; ANGIOTENSIN-II; BLOOD-FLOW; MONOCLONAL-ANTIBODIES; SOLID TUMORS; INTERSTITIAL HYPERTENSION; DRUG-DELIVERY; MICROVASCULAR ARCHITECTURE; NUDE-MICE; SCID MICE AB Cancer therapies using genes and other macromolecules might realize their full clinical potential if they could be delivered to tumor tissue in optimal quantities. Unfortunately, the compromised circulation within tumors poses a formidable resistance to adequate and uniform penetration of these agents. Previously, we have proposed elevated interstitial fluid pressure (IFP) as a major physiological barrier to delivery of macromolecules. Here we postulate that modulation of tumor microvascular pressure (MVP) and associated changes in IFP, would enhance macromolecular delivery into a solid tumor. To test our hypothesis, we altered tumor MVP by either periodic injection or continuous infusion of angiotensin II (AII) and measured the resulting changes in IFP and uptake of macromolecules. We used the nicotinyl hydrazine derivative of human polyclonal IgG (HYNIC-IgG) as a nonspecific macromolecule and CC49 antibody as a specific macromolecule. We found that both chronic and periodic modulation of tumor MVP enhances transvascular fluid filtration, leading to a 40% increase in total uptake of the specific antibody within 4 hr of its administration. Conversely, neither continuous nor periodic infusion of, AII induced any increase in uptake of nonspecific antibodies. Strategies to improve delivery of macromolecules and limitations of this approach are identified. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Imaging & Pharmaceut Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Fruit St, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu OI NETTI, PAOLO/0000-0002-2435-7181 FU NCI NIH HHS [R35-CA-56591] NR 51 TC 138 Z9 140 U1 2 U2 10 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 MAR 16 PY 1999 VL 96 IS 6 BP 3137 EP 3142 DI 10.1073/pnas.96.6.3137 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 177RH UT WOS:000079224500104 PM 10077650 ER PT J AU Gliatto, MF Rai, AK AF Gliatto, MF Rai, AK TI Evaluation and treatment of patients with suicidal ideation SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID RISK AB Suicidal ideation is more common than completed suicide. Most persons who commit suicide have a psychiatric: disorder at the time of death. Because many patients with psychiatric disorders are seen by family physicians and other primary care practitioners rather than by psychiatrists, it is important that these practitioners recognize the signs and symptoms of the psychiatric disorders (particularly alcohol abuse and major depression) that are associated with suicide. Although most patients with suicidal ideation do not ultimately commit suicide, the extent of suicidal ideation must be determined, including the presence of a suicide plan and the patient's means to commit suicide. C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Gliatto, MF (reprint author), Philadelphia Vet Affairs Med Ctr, 38th & Woodland Ave, Philadelphia, PA 19104 USA. NR 24 TC 36 Z9 37 U1 2 U2 5 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD MAR 15 PY 1999 VL 59 IS 6 BP 1500 EP 1506 PG 7 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 180BD UT WOS:000079364300013 PM 10193592 ER PT J AU Singh, JP Evans, JC Levy, D Larson, MG Freed, LA Fuller, DL Lehman, B Benjamin, EJ AF Singh, JP Evans, JC Levy, D Larson, MG Freed, LA Fuller, DL Lehman, B Benjamin, EJ TI Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (The Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID STRUCTURALLY NORMAL HEARTS; VALVULAR REGURGITATION; COLOR-DOPPLER; ROOT SIZE; HYPERTENSION; ECHOCARDIOGRAPHY; DISEASE; OBESITY; AGE AB Little information is available on the prevalence and determinants of valvular regurgitation in the general population. This study sought to assess the prevalence and clinical determinants of mitral (MR), tricuspid (TR), and aortic (AR) regurgitation in a population-based cohort. Color Doppler echocardiography was performed in 1,696 men and 1,893 women (aged 54 +/- 10 years) attending a routine examination at the Framingham Study. After excluding technically poor echocardiograms, MR, TR, and AR were qualitatively graded from trace to severe. Multiple logistic regression analysis was used to examine the association of clinical variables with MR and TR (more than or equal to mild severity) and AR (more than or equal to trace severity). MR and TR of more than or equal to mild severity was seen In 19.0% and 14.8% of men and 19.1% and 18.4% of women, respectively, and AR of more than or equal to trace severity in 13.0% of men and 8.5% of women. The clinical determinants of MR were age (odds ratio [OR] 1.3/9.9 years, 95% confidence interval [CI] 1.2 to 1.5), hypertension (OR 1.6; 95% CI 1.2 to 2.0), and body mass index (OR 0.8/4.3 kg/m(2); 95% CI 0.7 to 0.9). The determinants of TR were age (OR 1.5/9.9 years; 95% CI 1.3 to 1.7), body mass index (OR 0.7/4.3 kg/m(2): 95% CI 0.6 to 0.8), and female gender (OR 1.2; 95% CI 1.0 to 1.6). The determinants of AR were age (OR 2.3/9.9 years; 95% CI 2.0 to 2.7) and male gender (OR 1.6; 95% CI 1.2 to 2.1). A substantial proportion of healthy men and women had detectable valvular regurgitation by color Doppler echocardiography. These data provide population-based estimates for comparison with patients taking anorectic drugs. (C) 1999 by Excerpta Medico, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Prevent Med, Boston, MA 02118 USA. Beth Israel Hosp, Div Cardiol, Boston, MA 02215 USA. Beth Israel Hosp, Div Clin Epidemiol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. EM emelia@fram.nhlbi.nih.gov OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [2-RO1-NS-17950-11] NR 27 TC 392 Z9 404 U1 0 U2 6 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 1999 VL 83 IS 6 BP 897 EP 902 DI 10.1016/S0002-9149(98)01064-9 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 178AV UT WOS:000079244000015 PM 10190406 ER PT J AU Vescio, R Schiller, G Stewart, AK Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Tarantolo, S Sahebi, F Stiff, P Meharchard, J Schlossman, R Brown, R Tully, H Benyunes, M Jacobs, C Berenson, R DiPersio, J Anderson, K Berenson, J AF Vescio, R Schiller, G Stewart, AK Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Tarantolo, S Sahebi, F Stiff, P Meharchard, J Schlossman, R Brown, R Tully, H Benyunes, M Jacobs, C Berenson, R DiPersio, J Anderson, K Berenson, J TI Multicenter phase III trial to evaluate CD34(+) selected versus unselected autologous peripheral blood progenitor cell transplantation in multiple myeloma SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; NON-HODGKINS-LYMPHOMA; BREAST-CANCER; INTENSIVE THERAPY; RANDOMIZED TRIAL; MALIGNANT-CELLS; STEM-CELLS; ENGRAFTMENT; SUPPORT AB High-dose chemotherapy followed by autologous transplantation has been shown to improve response rates and survival in multiple myeloma and other malignancies. However, autografts frequently contain detectable tumor cells. Enrichment for stem cells using anti-CD34 antibodies has been shown to reduce autograft tumor contamination in phase I/II studies. To more definitively assess the safety and efficacy of CD34 selection, a phase ill study was completed in 131 multiple myeloma patients randomized to receive an autologous transplant with either CD34-selected or unselected peripheral blood progenitor cells after myeloablative therapy. Tumor contamination in the autografts was assessed by a quantitative polymerase chain reaction detection assay using patient-specific, complementarity-determining region (CDR) Ig gene primers before and after CD34 selection. A median 3.1 log reduction in contaminating tumor cells was achieved in the CD34 selected product using the CEPRATE SC System (CellPro, Inc, Bothell, WA). Successful neutrophil engraftment was achieved in all patients by day 15 and no significant between-arm difference for time to platelet engraftment occurred in patients who received an infused dose of at least 2.0 x 10(6) CD34(+) cells/kg. In conclusion, this phase III trial demonstrates that CD34-selection of peripheral blood progenitor cells significantly reduces tumor cell contamination yet provides safe and rapid hematologic recovery for patients receiving myeloablative therapy. (C) 1999 by The American Society of Hematology. C1 Univ Calif Los Angeles, W LA VAMC, Los Angeles, CA 90073 USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Univ S Florida, Miami, FL USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Nebraska, Omaha, NE 68182 USA. So Calif Kaiser Permanente Med Grp, Los Angeles, CA USA. Loyola Univ, Chicago, IL 60611 USA. Washington Univ, Sch Med, St Louis, MO USA. Dana Farber Canc Inst, Boston, MA 02115 USA. CellPro Inc, Bothell, WA USA. RP Vescio, R (reprint author), Univ Calif Los Angeles, W LA VAMC, 111-H W LA VAMC,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 51 TC 130 Z9 136 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 MAR 15 PY 1999 VL 93 IS 6 BP 1858 EP 1868 PG 11 WC Hematology SC Hematology GA 176RT UT WOS:000079166100011 PM 10068658 ER PT J AU Silverman, LB Gelber, RD Young, ML Dalton, VK Barr, RD Sallan, SE AF Silverman, LB Gelber, RD Young, ML Dalton, VK Barr, RD Sallan, SE TI Induction failure in acute lymphoblastic leukemia of childhood SO CANCER LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 17-21, 1997 CL DENVER, COLORADO SP Amer Soc Clin Oncol DE acute lymphoblastic leukemia; induction failure; hypoplastic bone marrow; M2 bone marrow; M3 bone marrow; survival ID BONE-MARROW TRANSPLANTATION; PEDIATRIC-ONCOLOGY-GROUP; RESIDUAL DISEASE; POOR-PROGNOSIS; COMBINATION CHEMOTHERAPY; COMPLETE REMISSION; CHILDREN; THERAPY; METHOTREXATE; CONSORTIUM AB BACKGROUND. Although it is widely accepted that failure to achieve complete remission (CR) portends a poor prognosis in childhood acute lymphoblastic leukemia (ALL), there is variability in the precise definition of induction failure and, to the authors' knowledge, few published data exist regarding the outcome of patients who are slow to achieve CR. METHODS. Between 1987-1995, 774 children with ALL were treated on 2 consecutive protocols and were evaluable to assess the time required to attain CR. The authors compared presenting characteristics and outcomes of patients based on their remission status after 1 month of induction chemotherapy: CR (n = 656), protracted hypoplasia (low peripheral blood counts and/or hypocellular marrow) (n = 95), and persistent leukemia (M2 or M3 bone marrow and/or evidence of extramedullary leukemia) (n = 23). The median follow-up was 5.2 years. RESULTS. Presenting features that predicted persistent leukemia included a leukocyte count > 100,000/mm(3) and T-cell phenotype. Approximately 91% of patients with persistent leukemia and 100% with protracted hypoplasia eventually achieved CR. The 5-year event free survival (EFS) (95% confidence intervals [95% CI] in parentheses) for patients with persistent leukemia after 1 month was 16% (95% CI, 0%, 31%), which was significantly worse (P < 0.001) than that for those who achieved CR within 1 month (5-year EFS, 82%; 95% CI, 79%, 86%) and that for those with protracted hypoplasia (5-year EFS, 79%; 95% CI, 70%, 87%). For patients with persistent leukemia, there was no significant difference in survival based on bone marrow status (M2 or M3) after 1 month or on the number of induction cycles received before achieving CR. CONCLUSIONS. Patients with persistent leukemia at the end of 1 month of therapy have a dismal prognosis, regardless of when they subsequently achieve CR. More intensive and/or novel therapies should be considered for this subset of patients. Cancer 1999;85:1395-404. (C) 1999 American Cancer Society. C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. McMaster Univ, Dept Pediat Hematol Oncol, Hamilton, ON, Canada. RP Silverman, LB (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 68484] NR 39 TC 38 Z9 40 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 1999 VL 85 IS 6 BP 1395 EP 1404 DI 10.1002/(SICI)1097-0142(19990315)85:6<1395::AID-CNCR25>3.0.CO;2-2 PG 10 WC Oncology SC Oncology GA 175KQ UT WOS:000079092900025 PM 10189148 ER PT J AU Chauhan, D Hideshima, T Treon, S Teoh, G Raje, N Yoshihimito, S Tai, YT Li, WW Fan, JG DeCaprio, J Anderson, KC AF Chauhan, D Hideshima, T Treon, S Teoh, G Raje, N Yoshihimito, S Tai, YT Li, WW Fan, JG DeCaprio, J Anderson, KC TI Functional interaction between retinoblastoma protein and stress-activated protein kinase in multiple myeloma cells SO CANCER RESEARCH LA English DT Article ID INDUCED APOPTOSIS; EXPRESSION; PHOSPHORYLATION; REQUIREMENT; DOMAIN; BINDS; DEATH; LINES; GENE AB previous studies have demonstrated that gamma-irradiation (IR)-induced apoptosis in multiple myeloma (MM) is associated with activation of stress-activated protein kinase (SAPK), In the present study, we examined the molecules downstream of SAPK/C-Jun N-terminal kinase (JNK), focusing on the role of retinoblastoma protein (Rb) during IR-induced MM cell apoptosis. The results demonstrate that IR activates SAPK/JNK, which associates with Rb both in viva and in vitro. Far Western blot analysis confirms that SAPK/JNK binds directly to Rb. IR-activated SAPK/JNK phosphorylates Rb, and deletion of the phosphorylation site in the COOH terminus domain of Rb abrogates phosphorylation of Rb by SAPK/JNK. Taken together, our results suggest that Rb is a target protein of SAPK/JNK and that the association of SAPK/JNK and Rb mediates IR-induced apoptosis in MM cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Therapeut, New York, NY 10021 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA50947] NR 25 TC 23 Z9 23 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 1999 VL 59 IS 6 BP 1192 EP 1195 PG 4 WC Oncology SC Oncology GA 175ZD UT WOS:000079125200006 PM 10096546 ER PT J AU Anderson, CF Rudd, CE Farber, DL AF Anderson, CF Rudd, CE Farber, DL TI Differential signaling pathways in memory and naive CD4 T lymphocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A940 EP A940 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901689 ER PT J AU Billman, GE Leaf, A AF Billman, GE Leaf, A TI Purified omega-3 fatty acids can prevent ventricular fibrillation induced by myocardial ischemia SO FASEB JOURNAL LA English DT Meeting Abstract C1 Ohio State Univ, Dept Physiol, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A761 EP A761 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900655 ER PT J AU Carroll, M Zhang, M Barrington, R AF Carroll, M Zhang, M Barrington, R TI Regulatory role of complement receptors CD21/CD35 in follicular survival of B cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A995 EP A995 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902013 ER PT J AU Carroll, MC Pozdnyakova, OO Paul, E Prodeus, AP Shen, L AF Carroll, MC Pozdnyakova, OO Paul, E Prodeus, AP Shen, L TI A critical role of complement in regulation of self-reactive B cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A955 EP A955 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901783 ER PT J AU Chandrasekhar, S Schwarz, C Abcouwer, SF AF Chandrasekhar, S Schwarz, C Abcouwer, SF TI HSP70 expression and HSF1 activation following heat shock is inhibited in human breast cells deprived of the amino acid glutamine SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Oncol Res Labs,Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A742 EP A742 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900549 ER PT J AU Chang, J Wasser, JS Knowlton, AA AF Chang, J Wasser, JS Knowlton, AA TI HSF activation and increased expression of HSP72 is mediated by stretch-activated channels in the isolated perfused rat heart SO FASEB JOURNAL LA English DT Meeting Abstract C1 Texas A&M Univ, Coll Vet Med, College Stn, TX 77843 USA. Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A769 EP A769 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900704 ER PT J AU Chu, S Tanaka, S Kaunitz, JD Montrose, MH AF Chu, S Tanaka, S Kaunitz, JD Montrose, MH TI In vivo confocal imaging of gastric surface pH SO FASEB JOURNAL LA English DT Meeting Abstract C1 Indiana Univ, Indianapolis, IN 46202 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A731 EP A731 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900484 ER PT J AU Dias, SR Schneider, H Hu, H Rudd, CE AF Dias, SR Schneider, H Hu, H Rudd, CE TI CTLA-4 negatively regulates apoptotic signals generated from the TCR. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A979 EP A979 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901920 ER PT J AU Gordon, MK Foley, JE Koch, M AF Gordon, MK Foley, JE Koch, M TI Type XX collagen, a new member of the fibril-associated (FACIT) family of collagens SO FASEB JOURNAL LA English DT Meeting Abstract C1 Rutgers State Univ, Dept Pharmacol & Toxicol, Rutgers Coll Pharm, Piscataway, NJ 08854 USA. Tufts Univ, Sch Med, Dept Anat & Cellular Biol, Boston, MA 02111 USA. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A1119 EP A1119 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902724 ER PT J AU Guerette, G Martin, M Raab, M Rudd, CE AF Guerette, G Martin, M Raab, M Rudd, CE TI SLP-76 is involved in CD28 signaling SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A954 EP A954 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901774 ER PT J AU Harley, JB Kirby, MY James, JA Kaufman, KM AF Harley, JB Kirby, MY James, JA Kaufman, KM TI Peptide mimics of a major lupus epitope of SmB/B '. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, US Dept Vet Affairs,Med Ctr, Oklahoma City, OK 73104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A958 EP A958 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901798 ER PT J AU Lu, L Quackenbush, EJ Wershil, BK AF Lu, L Quackenbush, EJ Wershil, BK TI Eotaxin contributes to mast cell-dependent eosinophil recruitment in substance P-induced cutaneous inflammation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Program Pediat GI Nutrit, Boston, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A658 EP A658 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900072 ER PT J AU Quinn, DA Volokov, A Hales, CA AF Quinn, DA Volokov, A Hales, CA TI Hyperoxia accelerates lung neutrophil recruitment in ventilator-induce lung injury SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Pulm Crit Care, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A821 EP A821 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900997 ER PT J AU Raab, M Kang, H Zhu, X daSilva, AJ Rudd, CE AF Raab, M Kang, H Zhu, X daSilva, AJ Rudd, CE TI FYB-FYN-SLP-76 complex assembly defines a second TcRz/CD3 mediated tyrosine phosphorylation pathway that regulates lymphokine production in T-cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A945 EP A945 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901719 ER PT J AU Sabolic, I Herak-Kramberger, CM Smith, PJS Brown, D Breton, S AF Sabolic, I Herak-Kramberger, CM Smith, PJS Brown, D Breton, S TI Cadmium (Cd) inhibits vacuolar proton-ATPase (V-ATPase)-mediated acidification in the rat epididymis SO FASEB JOURNAL LA English DT Meeting Abstract C1 IMI, Zagreb 10001, Croatia. Marine Biol Lab, Woods Hole, MA 02543 USA. Massachusetts Gen Hosp, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A1031 EP A1031 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132902217 ER PT J AU Sehneeberger, EE Vu, Q LeBlanc, BW Doerschuk, CM AF Sehneeberger, EE Vu, Q LeBlanc, BW Doerschuk, CM TI Migration of dendritic cell (DC) precursors to the lung is impaired in CD18 mutant mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A660 EP A660 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900081 ER PT J AU Sevigny, J Enjyoji, K Lin, Y Esch, JSA Imai, M Rosenberg, RD Robson, SC AF Sevigny, J Enjyoji, K Lin, Y Esch, JSA Imai, M Rosenberg, RD Robson, SC TI Disordered hemostasis and thromboregulation in cd39-deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Massuachusetts Inst Technol, Boston, MA USA. RI Sevigny, Jean/E-8039-2012 OI Sevigny, Jean/0000-0003-2922-1600 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A839 EP A839 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901106 ER PT J AU Xn, J Irigoyen, M Gallagher, D Alper, CA AF Xn, J Irigoyen, M Gallagher, D Alper, CA TI Association between anti-IgA antibodies and IgD deficiency in IgA-deficient patients SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A674 EP A674 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132900161 ER PT J AU Yu, YM Ryan, CM Tompkins, RG Young, VR AF Yu, YM Ryan, CM Tompkins, RG Young, VR TI Arginine kinetics in severe burn injury. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 15 PY 1999 VL 13 IS 5 SU S BP A876 EP A876 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 228JG UT WOS:000082132901320 ER PT J AU Brady, KP Dushkin, H Fornzler, D Koike, T Magner, F Her, H Gullans, S Segre, GV Green, RM Beier, DR AF Brady, KP Dushkin, H Fornzler, D Koike, T Magner, F Her, H Gullans, S Segre, GV Green, RM Beier, DR TI A novel putative transporter maps to the osteosclerosis (oc) mutation and is not expressed in the oc mutant mouse SO GENOMICS LA English DT Article ID MOLECULAR-CLONING; OC/OC MICE; CELLS; LOCALIZATION; KIDNEY; LOCI AB The phenotype of mice homozygous for the osteosclerosis (oc) mutation includes osteopetrosis, and a variety of studies demonstrate that osteoclasts in these mice are present but nonfunctional. We have identified a novel gene that has homology to a family of la-transmembrane domain proteins with transport functions and maps to proximal mouse chromosome 19, in a region to which the oc mutation has been previously assigned. The putative transporter is abundant in normal kidney, but its expression is markedly reduced in kidneys from oc/oc mice when tested using Northern and Western analyses. Southern analysis of this gene, which we call Roct (reduced in oc transporter), demonstrates that it is intact and unrearranged in oc/oc mice. In situ studies show that Roct is expressed in developing bone. We propose that the absence of Roct expression results in an osteopetrosis phenotype in mice. (C) 1999 Academic Press. C1 Brigham & Womens Hosp, Div Genet, Harvard Med Sch, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Harvard Med Sch, Boston, MA 02115 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Illinois, Coll Med, Sect Digest & Liver Dis, Chicago, IL 60612 USA. RP Beier, DR (reprint author), Brigham & Womens Hosp, Div Genet, Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK45639, DK36031] NR 26 TC 60 Z9 61 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 1999 VL 56 IS 3 BP 254 EP 261 DI 10.1006/geno.1998.5722 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 180MP UT WOS:000079390000003 PM 10087192 ER PT J AU Schaefer, L Beermann, ML Miller, JB AF Schaefer, L Beermann, ML Miller, JB TI Coding sequence, genomic organization, chromosomal localization, and expression pattern of the signalosome component Cops2: The mouse homologue of Drosophila alien SO GENOMICS LA English DT Article ID RETINOID-X-RECEPTOR; HORMONE RESPONSE ELEMENT; THYROID-HORMONE; MUSCLE DIFFERENTIATION; LIGHT CONTROL; GENE; PROTEIN; ACID; TRIIODOTHYRONINE; TRANSCRIPTION AB The Drosophila alien gene is highly homologous to the human thyroid receptor interacting protein, TRIP15/COPS2, which is a component of the recently identified signalosome protein complex. We identified the mouse homologue of Drosophila alien through homology searches of the EST database. We found that the mouse cDNA encodes a predicted 443-amino-acid protein, which migrates at similar to 50 kDa. The gene for the mouse alien homologue, named Cops2, includes 12 coding exons spanning similar to 30 kb of genomic DNA on the central portion of mouse chromosome 2. Mouse Cops2 is widely expressed in embryonic, fetal, and adult tissues beginning as early as E7.5. Mouse Cops2 cDNA hybridizes to two mRNA bands in all tissues at similar to 2.3 and similar to 4 kb, with an additional similar to 1.9-kb band in liver. Immunostaining of native and epitope tagged proteins localized the mouse Cops2 protein in both the cytoplasm and the nucleus, with larger amounts in the nucleus in some cells. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, Myogenesis Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Miller, JB (reprint author), Massachusetts Gen Hosp, Myogenesis Res Lab, 149 13th St, Charlestown, MA 02129 USA. EM Miller@helix.mgh.harvard.edu NR 29 TC 19 Z9 20 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 1999 VL 56 IS 3 BP 310 EP 316 DI 10.1006/geno.1998.5728 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 180MP UT WOS:000079390000009 PM 10087198 ER PT J AU Tishler, RB Busse, PM Norris, CM Rossi, R Poulin, M Thornhill, L Costello, R Peters, ES Colevas, AD Posner, MR AF Tishler, RB Busse, PM Norris, CM Rossi, R Poulin, M Thornhill, L Costello, R Peters, ES Colevas, AD Posner, MR TI An initial experience using concurrent paclitaxel and radiation in the treatment of head and neck malignancies SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 17-21, 1997 CL DENVER, COLORADO SP Amer Soc Clin Oncol DE paclitaxel; radiation; head and neck; combined modality therapy ID SQUAMOUS-CELL CARCINOMA; HIGH-DOSE LEUCOVORIN; PHASE-I TRIAL; TUMOR RADIORESPONSE; ACTIVE-DRUG; TAXOL; CANCER; CHEMOTHERAPY; RADIOTHERAPY; THERAPY AB Background: Combined modality therapy plays a central role in the management of head and neck malignancies. This study examined the feasibility and preliminary results of treating a group of patients using concurrent bolus paclitaxel (Taxol(TM)) and radiation therapy. Methods: Fourteen patients with a median age of 56 years (range 42-81) were treated. Paclitaxel was given every 3 weeks at a dose of 100 mg/m(2) concurrently with external beam radiation. The patients treated included those who had failed to achieve a complete response (CR) to induction chemotherapy with cisplatin, 5-fluorouracil, and leucovorin (PFL), or who had locally advanced disease not previously treated. Results: Median follow-up from the initiation of treatment is 40 months (range 23-48). The majority of patients (13/14) achieved clinical CRs at the primary site. The development of responses was characterized by a long time course. Three patients who were nonresponders (NRs) to induction PFL chemotherapy were treated. One was a clinical CR at the primary site, one did not achieve a CR, and the other had residual disease in the neck. Four patients have failed, one with local-regional disease, one with a marginal failure, one with distant metastases, and one was not rendered disease-free by the treatment. As expected, significant local toxicity was observed. Most patients were managed with the aid of a percutaneous endoscopic gastrostomy (PEG). Two patients experienced significant moist desquamation and required treatment breaks of greater than 1 week. Conclusion: Paclitaxel can be given on a 3-week schedule at 100 mg/m(2) concurrently with radiation. The preliminary results indicate good local responses and acceptable toxicity. This treatment approach merits further study in the treatment of head and neck malignancies, and should be considered as an option in other sites. (C) 1999 Elsevier Science Inc. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Joint Ctr Radiat Therapy, Boston, MA 02215 USA. RP Tishler, RB (reprint author), Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. EM rtishler@jcrt.harvard.edu OI /0000-0003-4928-6532 NR 35 TC 27 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 1999 VL 43 IS 5 BP 1001 EP 1008 DI 10.1016/S0360-3016(98)00533-1 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 178RD UT WOS:000079279100010 PM 10192347 ER PT J AU Flynn, DF Kresl, JJ Sheldon, JM AF Flynn, DF Kresl, JJ Sheldon, JM TI The employment status of 1995 graduates from radiation oncology training programs in the United States SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE manpower; workforce; radiation oncology ID RESIDENT PHYSICIANS; 21ST CENTURY; RADIOLOGY; PATTERNS; CARE AB Purpose: To quantify the employment status of 1995 graduates of radiation oncology training programs in the United States. Methods and Materials: All senior residents (149) and fellows (36) who completed training in 1995 were mailed an employment survey questionnaire by the Association of Residents in Radiation Oncology (ARRO). Telephone follow-up of nonrespondents achieved a 100% response rate. Twenty graduates who chose to continue training and five who returned to their home countries were removed from the study. Of the 160 who attempted to enter the U.S. workforce, 106 were men and 54 were women. Initial job status and job status at 6-8 months following graduation were determined. Results: Unemployment was 6.9% at graduation and 4.4% at 6-8 months. Underemployment (part-time employment) was 10.6% at graduation and 11.9% at 6-8 months postgraduation. Of those working part-time 6-8 months after graduation, 63% (12 of 19) did so involuntarily after unsuccessfully seeking full-time employment. For the 20 graduates who chose to continue training with fellowships, seven (35%) did so solely to avoid unemployment, four (20%) were partially influenced by the job market, and nine (45%) were not influenced by the job market. Adverse employment search outcome was defined as being either unemployed as a radiation oncologist or involuntarily working part-time. Excluding those who chose to work part-time, a total of 19 (11.9%) graduates at 6-8 months following graduation, compared to 22 (13.8%) at graduation, were either unemployed or involuntarily working part-time. In terms of gender, this represented 18.5% (10 of 54) of females and 8.6% (9 of 105) of males. In terms of geographic restrictions in the job search, 56% of males and 70% of females with an adverse employment outcome limited their job search to certain parts of the country. This compares to 62% of all graduates in this study with geographic restrictions in their job search. In terms of perceptions of the workforce and employment opportunities, 95% of all graduates believed there was an oversupply of radiation oncologists and 95.5% believed the job market was worse than what they had anticipated on entering training. Only 42.8% of all graduates were satisfied with the job opportunities available to them. A significant number of private practice positions (41%) did not offer a partnership track, and those that did so had an increased median employment period before partnership (3.25 years) compared to previous years. Conclusion: This is the only employment survey for any specialty in which a 100% response rate was achieved. Upon graduation, a significant number of residents and fellows were either unemployed or involuntarily underemployed. The job market absorbed only a fraction of them at 6-8 months. Most graduates, including those employed full-time, mere not satisfied with the practice opportunities available to them during their job search. Many private-sector jobs did not offer a partnership track, and those that did required an increased employment period. A higher rate of involuntary part-time employment was seen for female graduates. Geographic restrictions in job search alone could not account for graduates being unemployed or underemployed, and could not account for gender differences. An overwhelming majority of 1995 radiation oncology graduates believed that the job market had deteriorated and that there was an oversupply of radiation oncologists. As one of two major studies tracking the employment status of radiation oncology graduates, we believe this study to be superior in methodology. We also believe this study presents data in a manner useful to medical students, training program directors, and healthcare policymakers. (C) 1999 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mayo Clin, Div Radiat Oncol, Rochester, MN USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Flynn, DF (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 24 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 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 1999 VL 43 IS 5 BP 1075 EP 1081 DI 10.1016/S0360-3016(98)00476-3 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 178RD UT WOS:000079279100022 PM 10192359 ER PT J AU Ambati, BK Ambati, J Azar, N Stratton, L Schmidt, E AF Ambati, BK Ambati, J Azar, N Stratton, L Schmidt, E TI Periorbital and orbital cellulitis pre- and post-H-influenzae vaccination SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1999 VL 40 IS 4 MA 140B100 BP S27 EP S27 PG 1 WC Ophthalmology SC Ophthalmology GA 178MF UT WOS:000079269200141 ER PT J AU Ambati, J You, T Gragoudas, ES Miller, JW Delori, FC Adamis, AP AF Ambati, J You, T Gragoudas, ES Miller, JW Delori, FC Adamis, AP TI Transscleral delivery of antibodies to the posterior segment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1999 VL 40 IS 4 MA 457B417 BP S86 EP S86 PG 1 WC Ophthalmology SC Ophthalmology GA 178MF UT WOS:000079269200457 ER PT J AU Gasch, AT Wang, P Pasquale, LR AF Gasch, AT Wang, P Pasquale, LR TI An assessment of glaucoma awareness and perceptions regarding glaucoma testing SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Sch Publ Hlth, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1999 VL 40 IS 4 MA 426B386 BP S80 EP S80 PG 1 WC Ophthalmology SC Ophthalmology GA 178MF UT WOS:000079269200427 ER PT J AU Hernandez-Quintela, E Azar, DT O'Reilly, MS Ye, HQ Lu, PC Rachid, MD AF Hernandez-Quintela, E Azar, DT O'Reilly, MS Ye, HQ Lu, PC Rachid, MD TI The role of angiostatin in the cornea after wounding. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1999 VL 40 IS 4 MA 521B481 BP S97 EP S97 PG 1 WC Ophthalmology SC Ophthalmology GA 178MF UT WOS:000079269200521 ER PT J AU Lu, M Amano, S Gariand, R Rohan, R Qin, W Adamis, A AF Lu, M Amano, S Gariand, R Rohan, R Qin, W Adamis, A TI Insulin increases vascular endothelial growth factor expression in retinal cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Childrens Hosp, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1999 VL 40 IS 4 MA 43B3 BP S9 EP S9 PG 1 WC Ophthalmology SC Ophthalmology GA 178MF UT WOS:000079269200044 ER PT J AU Moromizato, Y Khosrof, SA Adamis, AP AF Moromizato, Y Khosrof, SA Adamis, AP TI A mouse model of endogenous VEGF-dependent corneal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1999 VL 40 IS 4 MA 519B479 BP S97 EP S97 PG 1 WC Ophthalmology SC Ophthalmology GA 178MF UT WOS:000079269200519 ER PT J AU Pasquale, LR Farra, T AF Pasquale, LR Farra, T TI The relation between steroid use and normal tension glaucoma: A case-control study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. New England Coll Optometry, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1999 VL 40 IS 4 MA 356B316 BP S66 EP S66 PG 1 WC Ophthalmology SC Ophthalmology GA 178MF UT WOS:000079269200357 ER PT J AU Wen, Y Sachs, G AF Wen, Y Sachs, G TI Lipocortin-5 may function as a signaling protein for vascular endothelial growth factor receptor-2/Flk-1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, W Los Angeles VA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 1999 VL 40 IS 4 MA 47B7 BP S10 EP S10 PG 1 WC Ophthalmology SC Ophthalmology GA 178MF UT WOS:000079269200048 ER PT J AU Stremmel, C Greenfield, EA Howard, E Freeman, GJ Kuchroo, VK AF Stremmel, C Greenfield, EA Howard, E Freeman, GJ Kuchroo, VK TI B7-2 expressed on EL4 lymphoma suppresses antitumor immunity by an interleukin 4-dependent mechanism SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T lymphoma; B7-2; immune suppression; interleukin 4; interleukin 10 ID T-CELL PROLIFERATION; CD28 RECEPTOR FAMILIES; COSTIMULATORY MOLECULES; COUNTER-RECEPTOR; 2ND LIGAND; CTLA-4; ANTIGEN; LYMPHOCYTES; INDUCTION; CD86 AB For T cells to become functionally activated they require at least two signals. The B7 costimulatory molecules B7-1 and B7-2 provide the "second signal" pivotal for T cell activation. In this report, we studied the relative roles of B7-1 and B7-2 molecules in the induction of antitumor immunity to the T cell thymoma, EL4. We generated EL4 tumor cells that expressed B7-1, B7-2, and B7-1+B7-2 by transfecting murine cDNAs. Our results demonstrate that EL4-B7-1 cells are completely rejected in syngeneic mice. Unlike EL4-B7-1 cells, we fmd that EL4-B7-2 cells are not rejected but progressively grow in the mice. A B7-1- and B7-2-EL4 double transfectant was generated by introducing B7-2 cDNA into the EL4-B7-1 tumor line that regressed in vivo. The EL4-B7-1+B7-2 double transfectant was not rejected when implanted into syngeneic mice but progressively grew to produce tumors. The double transfectant EL4 cells could costimulate T cell proliferation that could be blocked by anti-B7-1 antibodies, anti-B7-2 antibodies, or hCTLA4 immunoglobulin, showing that the B7-1 and B7-2 molecules expressed on the EL4 cells were functional. In vivo, treatment of mice implanted with double-transfected EL4 cells with anti-B7-2 monoclonal antibody resulted in tumor rejection. Furthermore, the EL4-B7-2 and EL4-B7-1+B7-2 cells, but not the wild-type EL4 cells, were rejected in interleukin 4 (IL-4) knockout mice. Our data suggests that B7-2 expressed on some T cell tumors inhibits development of antitumor immunity, and IL-4 appears to play a critical role in abrogation of the antitumor immune response. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Kuchroo, VK (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, 77 Ave Pasteur, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 25082, P01 AI039671, R37 AI025082, R01 AI-39671-01A1, R01 AI025082]; NINDS NIH HHS [R01 NS-35685, R01 NS035685] NR 38 TC 38 Z9 38 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 15 PY 1999 VL 189 IS 6 BP 919 EP 930 DI 10.1084/jem.189.6.919 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 177RX UT WOS:000079225800004 PM 10075975 ER PT J AU Nikolic, B Gardner, JP Scadden, DT Arn, JS Sachs, DH Sykes, M AF Nikolic, B Gardner, JP Scadden, DT Arn, JS Sachs, DH Sykes, M TI Normal development in porcine thymus grafts and specific tolerance of human T cells to porcine donor MHC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SCID-HU MOUSE; ACQUIRED IMMUNODEFICIENCY SYNDROME; TRANSPLANTATION; INFECTION; RECONSTITUTION; REPERTOIRE; HIV-1; RETROVIRUS; DISEASE; BARRIER AB The induction of T cell tolerance is likely to play an essential role in successful xenotransplantation in humans. In this study, we show that porcine thymus grafts in immunodeficient mice support normal development of polyclonal, functional human T cells. These T cells were specifically tolerant to MBC Ags of the porcine thymus donor and responded to nondonor porcine xenoantigens and alloantigens, Exogenous IL-2 did not abolish tolerance, suggesting central clonal deletion rather than anergy as the likely tolerance mechanism, Our study suggests that the thymic transplantation approach to achieving tolerance with restoration of immunocompetence may be applicable to xenotransplantation of pig tissues to humans. C1 Harvard Univ, Massachusetts Gen Hosp,Sch Med, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp,Sch Med, Div Expt Hematol, AIDS Res Ctr, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp,Sch Med, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU PHS HHS [P01 A1 39755] NR 32 TC 49 Z9 55 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1999 VL 162 IS 6 BP 3402 EP 3407 PG 6 WC Immunology SC Immunology GA 175QB UT WOS:000079105000037 PM 10092795 ER PT J AU Edinger, JW Bonneville, M Scotet, E Houssaint, E Schumacher, HR Posnett, DN AF Edinger, JW Bonneville, M Scotet, E Houssaint, E Schumacher, HR Posnett, DN TI EBV gene expression not altered in rheumatoid synovia despite the presence of EBV antigen-specific T cell clones SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; POLYMERASE CHAIN-REACTION; TUMOR-NECROSIS-FACTOR; SJOGRENS-SYNDROME; HUMAN CYTOMEGALOVIRUS; ARTHRITIS PATIENTS; PERIPHERAL-BLOOD; B-CELLS; FLUID LYMPHOCYTES; LYTIC REPLICATION AB T cells infiltrating the rheumatoid arthritis (RA) joint are oligoclonal, implicating an Ag-driven process, but the putative joint-specific Ags remain elusive, Here we examine expression of selected EBV genes in RA synovia and find no abnormal expression in RA, DNA of CMV and EBV was detectable by PCR in the synovial tissue of RA, RNA of several latent and lytic EBV genes was also detectable. However, there were no differences in EBV gene expression in synovial tissues or peripheral blood when comparing RA with osteoarthritis, Gulf War syndrome, and other disease controls, RA synovia with highly expanded CD8 T cell clones reactive with defined EBV peptide Ags presented by HLA class I alleles lacked evidence of abnormal mRNA expression for the relevant EBV Ag (BZLF1) or lacked amplifiable mRNA (BMLF1), Thus, local production of EBV Ags in synovial tissues may not be the cause of the accumulation of T cell clones specific for these Ags, Instead, APCs loaded with processed EBV peptides may migrate to the synovium, Alternatively, EBV-specific T cell clones may be generated in other tissues and then migrate to synovia, perhaps due to cross-reactive joint-specific Ags or because of expression of homing receptors. C1 Cornell Univ, Weill Med Coll, Grad Sch Med Sci, Program Immunol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Inst Biol, INSERM, U463, Nantes, France. RP Edinger, JW (reprint author), Cornell Univ, Weill Med Coll, Grad Sch Med Sci, Program Immunol, 1300 York Ave,Box 56, New York, NY 10021 USA. RI SCOTET, Emmanuel/L-2576-2015 FU NIAID NIH HHS [R0-1 AI22333]; PHS HHS [R0-131140] NR 76 TC 29 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1999 VL 162 IS 6 BP 3694 EP 3701 PG 8 WC Immunology SC Immunology GA 175QB UT WOS:000079105000074 PM 10092832 ER PT J AU Wagner, R Leschonsky, B Harrer, E Paulus, C Weber, C Walker, BD Buchbinder, S Wolf, H Kalden, JR Harrer, T AF Wagner, R Leschonsky, B Harrer, E Paulus, C Weber, C Walker, BD Buchbinder, S Wolf, H Kalden, JR Harrer, T TI Molecular and functional analysis of a conserved CTL epitope in HIV-1 p24 recognized from a long-term nonprogressor: Constraints on immune escape associated with targeting a sequence essential for viral replication SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; MAJOR HOMOLOGY REGION; REVERSE-TRANSCRIPTASE; DISEASE PROGRESSION; IN-VIVO; INFECTION; RESPONSES; CELLS; AIDS AB It has been hypothesized that sequence variation within CTL epitopes leading to immune escape plays a role in the progression of HIV-1 infection. Only very limited data exist that address the influence of biologic characteristics of CTL epitopes on the emergence of immune escape variants and the efficiency of suppression of HIV-1 by CTL. In this report, we studied the effects of HIV-1 CTL epitope sequence variation on HIV-1 replication. The highly conserved HLA-B14-restricted CTL epitope DRFYK-TLRAE in HIV-1 p24 was examined, which had been defined as the immunodominant CTL epitope in a long-term nonprogressing individual. We generated a set of viral mutants on an HX10 background differing by a single conservative or nonconservative amino acid substitution at each of the P1 to P9 amino acid residues of the epitope, All of the nonconservative amino acid substitutions abolished viral infectivity and only 5 of 10 conservative changes yielded replication-competent virus. Recognition of these epitope sequence variants by CTL was tested using synthetic peptides, All mutations that abrogated CTL recognition strongly impaired viral replication, and all replication-competent viral variants were recognized by CTL, although some variants with a lower efficiency. Our data indicate that this CTL epitope is located within a viral sequence essential for viral replication. Targeting CTL epitopes within functionally important regions of the HIV-1 genome could limit the chance of immune evasion. C1 Univ Erlangen Nurnberg, Inst Clin Immunol, Dept Med 3, D-91054 Erlangen, Germany. Univ Regensburg, Inst Med Microbiol, Regensburg, Germany. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Dept Publ Hlth, AIDS Off, San Francisco, CA 94140 USA. RP Harrer, T (reprint author), Univ Erlangen Nurnberg, Inst Clin Immunol, Dept Med 3, Krankenhausstr 12, D-91054 Erlangen, Germany. NR 53 TC 58 Z9 60 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1999 VL 162 IS 6 BP 3727 EP 3734 PG 8 WC Immunology SC Immunology GA 175QB UT WOS:000079105000078 PM 10092836 ER PT J AU Hart, AC Kass, J Shapiro, JE Kaplan, JM AF Hart, AC Kass, J Shapiro, JE Kaplan, JM TI Distinct signaling pathways mediate touch and osmosensory responses in a polymodal sensory neuron SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Caenorhabditis elegans; osmosensation; mechanosensation; neurodegeneration; OSM-10; eos-1; eos-2; degenerin ID NEMATODE CAENORHABDITIS-ELEGANS; GLR-1 GLUTAMATE-RECEPTOR; MAP KINASE CASCADE; C-ELEGANS; MECHANOSENSITIVE CHANNELS; TRANSDUCTION PATHWAY; EXTRACELLULAR DOMAIN; SUPRAOPTIC NEURONS; NERVOUS-SYSTEM; PROTEIN AB The Caenorhabditis elegans ASH sensory neurons mediate responses to nose touch, hyperosmolarity, and volatile repellent chemicals. We show here that distinct signaling pathways mediate the responses to touch and hyperosmolarity. ASH neurons distinguish between these stimuli because habituation to nose touch has no effect on the response to high osmolarity or volatile chemicals (1-octanol). Mutations in osm-10 eliminate the response to hyperosmolarity but have no effect on responses to nose touch or to volatile repellents. OSM-10 is a novel cytosolic protein expressed in ASH and three other classes of sensory neurons. Mutations in two other osmosensory-defective genes, eos-1 and eos-2, interact genetically with osm-10. Our analysis suggests that nose touch sensitivity and osmosensation occur via distinct signaling pathways in ASH and that OSM-10 is required for osmosensory signaling. C1 Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. RP Hart, AC (reprint author), Harvard Univ, Sch Med, Dept Pathol, 149-7202 13th St, Charlestown, MA 02129 USA. FU NIGMS NIH HHS [R01 GM057918, R01 GM057918-01A1]; NINDS NIH HHS [NS32196] NR 36 TC 94 Z9 114 U1 1 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 1999 VL 19 IS 6 BP 1952 EP 1958 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 173BQ UT WOS:000078961400006 PM 10066248 ER PT J AU Leverenz, JB Wilkinson, CW Wamble, M Corbin, S Grabber, JE Raskind, MA Peskind, ER AF Leverenz, JB Wilkinson, CW Wamble, M Corbin, S Grabber, JE Raskind, MA Peskind, ER TI Effect of chronic high-dose exogenous cortisol on hippocampal neuronal number in aged nonhuman primates SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cortisol; aging; nonhuman primate; hippocampus; stereology; CSF cortisol ID PROLONGED GLUCOCORTICOID EXPOSURE; PYRAMIDAL NEURONS; STRESS; MEMORY; DISEASE; VOLUME; BRAIN; RATS AB Chronic exposure to increased glucocorticoid concentrations appears to lower the threshold for hippocampal neuronal degeneration in the old rat. It has been proposed that increased brain exposure to glucocorticoids may lower the threshold far hippocampal neuronal degeneration in human aging and Alzheimer's disease. Here, we asked whether chronic administration of high-dose cortisol to older nonhuman primates decreases hippocampal neuronal number as assessed by unbiased stereological counting methodology Sixteen Macaca nemestrina (pigtailed macaques) from 18 to 29 years of age were age-, sex-, and weight-matched into pairs and randomized to receive either high-dose oral hydrocortisone (cortisol) acetate (4-6 mg/kg/d) or placebo in twice daily palatable treats for 12 months. Hypothalamic pituitary-adrenal activity was monitored by measuring plasma adrenocorticotropin and cortisol, 24 hr urinary cortisol, and CSF cortisol. Urinary, plasma, and CSF cortisol were elevated, and plasma adrenocorticotropin was reduced in the active treatment group. Total hippocampal volume, subfield volumes, subfield neuronal density, and subfield total neuronal number did not differ between the experimental groups. These findings suggest that chronically elevated cortisol concentrations, in the absence of stress, do not produce hippocampal neuronal loss in nonhuman primates. C1 Vet Affairs Puget Sound Hlth Care syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Washington Reg Primate Res Ctr, Seattle, WA 98195 USA. RP Peskind, ER (reprint author), Vet Affairs Puget Sound Hlth Care syst, Mental Illness Res Educ & Clin Ctr, 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NCRR NIH HHS [2P51RR00166]; NIA NIH HHS [AGO6136] NR 28 TC 126 Z9 130 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 1999 VL 19 IS 6 BP 2356 EP 2361 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 173BQ UT WOS:000078961400043 PM 10066285 ER PT J AU Gutsmann-Conrad, A Pahlavani, MA Heydari, AR Richardson, A AF Gutsmann-Conrad, A Pahlavani, MA Heydari, AR Richardson, A TI Expression of heat shock protein 70 decreases with age in hepatocytes and splenocytes from female rats SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article; Proceedings Paper CT 2nd International NILS Workshop on Longevity Sciences - Roles of Protein in Aging and Age-Associated Disorders CY NOV 29-30, 1997 CL OBU, JAPAN SP NILS DE Liver; spleen; heat shock proteins; Hsp70; heat shock transcription factor ID TRANSCRIPTION FACTOR; MESSENGER-RNA; DNA-BINDING; LIVER-MICROSOMES; HSP70; PROMOTER; CLONING; CELLS; GENE; CYTOCHROME-P-450 AB A decline in the induction of heat shock protein 70 (hsp70) expression with age has been shown to occur in a variety of tissues from male rodents. Because the age-related change in the expression of many genes often differ in male and female rodents, we have measured the induction of hsp70 expression in hepatocytes and splenocytes from young/adult (4-8 months) and old (20-22 months) female Fischer 344 rats. Hepatocytes and splenocytes isolated from old female rats showed a marked decrease in the induction of hsp70 mRNA and protein levels by heat shock when compared to hepatocytes and splenocytes isolated from young/adult female rats. Because the heat shock transcription factor HSF1 mediates the heat-induced transcription of hsp70, the effect of age on HSFI was also studied. The ability of extracts from heat-shocked splenocytes to bind to the heat shock element (HSE) decreased with age. Interestingly, the levels of HSFI protein were similar in splenocytes and hepatocytes from old female rats compared to young/adult female rats, even though the levels of HSE-binding were lower for splenocytes isolated from old rats. In this study, we show an age-related decline in the expression of hsp70, and this decline was similar to what we had previously observed in male Fischer 344 rats. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Geriatr Res Educ & Clin Ctr 182, S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. RP Richardson, A (reprint author), Geriatr Res Educ & Clin Ctr 182, S Texas Vet Hlth Care Syst, Audie L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG01548] NR 43 TC 28 Z9 32 U1 0 U2 1 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 MAR 15 PY 1999 VL 107 IS 3 BP 255 EP 270 DI 10.1016/S0047-6374(98)00132-8 PG 16 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 192VC UT WOS:000080099400005 PM 10360681 ER PT J AU Tatarkiewicz, K Hollister-Lock, J Quickel, RR Colton, CK Bonner-Weir, S Weir, GC AF Tatarkiewicz, K Hollister-Lock, J Quickel, RR Colton, CK Bonner-Weir, S Weir, GC TI Reversal of hyperglycemia in mice after subcutaneous transplantation of macroencapsulated islets. SO TRANSPLANTATION LA English DT Article ID DIABETIC NUDE-MICE; BETA-CELL MASS; INSULIN-SECRETION; DIFFUSION CHAMBER; POTENTIAL SOURCE; XENOTRANSPLANTATION; PANCREAS; XENOGRAFTS; RAT; IMMUNOSUPPRESSION AB Background. Macroencapsulated islets can reverse hyperglycemia in diabetic animals when transplanted i.p. or into the fat pad. The s.c. space is an attractive site for such transplantation because macrocapsules can be implanted with local anesthesia and be easily removed or reloaded with fresh islets. Methods. Immunoprotective 20 mu l ported devices were transplanted under the skin of Streptozocin-diabetic nude mice. Devices were loaded with 1200 rat islets in culture medium or in alginate. Empty devices were implanted for 2 weeks and then loaded with islets. Normal mice and mice with islets transplanted under the renal capsule or under the skin were used as controls. Seven weeks after transplantation, an intraperitoneal glucose tolerance test (IPGTT) was performed, followed by implant removal. Results. Three weeks after transplantation, normal brood glucose levels were observed in all animals. Compared with those of normal controls, IPGTTs showed accelerated blood glucose clearance in mice transplanted with islets either within devices or beneath the kidney capsule. Fasted transplanted mice were hypoglycemic before glucose injection and 2 hr later. After removal of the implants, all recipient mice returned to hyperglycemia. Histological evaluation revealed viable islet cells and a network of close vascular structures outside the devices, Conclusions. Macroencapsulated islets transplanted into the s.c, space were able to survive and regulate blood glucose levels in mice. The observed differences in glucose metabolism between normal and transplanted mice may be attributed to the site of transplantation and to the use of rat islets, which have a different set point for glucose induced insulin release. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-35449, DK-36836, DK 50657] NR 29 TC 48 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 1999 VL 67 IS 5 BP 665 EP 671 DI 10.1097/00007890-199903150-00005 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 178NU UT WOS:000079273300005 PM 10096520 ER PT J AU Pascual, M Vallhonrat, H Cosimi, AB Tolkoff-Rubin, N Colvin, RB Delmonico, FL Ko, DSC Schoenfeld, DA Williams, WW AF Pascual, M Vallhonrat, H Cosimi, AB Tolkoff-Rubin, N Colvin, RB Delmonico, FL Ko, DSC Schoenfeld, DA Williams, WW TI The clinical usefulness of the renal allograft biopsy in the cyclosporine era - A prospective study SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 24th Annual Scientific Meeting of the American-Society-of-Transplant-Surgeons CY MAY, 1998 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surgeons ID TRANSPLANTATION; MANAGEMENT; REJECTION AB Background. The renal allograft biopsy is generally accepted as the gold standard for clarifying the cause of renal dysfunction, However, the clinical usefulness of this procedure has rarely been studied prospectively, nor have most studies included follow-up of patients to delineate the influence of the biopsy on clinical outcome. In this study, we evaluated prospectively the clinical usefulness of the allograft biopsy in renal transplant recipients receiving cyclosporine (CyA). Methods. During a 21-month period, 82 biopsies were performed. In 54 instances (47 patients), we outlined a presumed diagnosis and tentative treatment plan before the procedure. After the biopsy, a definitive diagnosis was made and an appropriate patient management approach was instituted. We analyzed the incidence of change in patient management that resulted from histological findings. All patients were followed to monitor their response to treatment and allograft survival. In cases of biopsy-proven acute cellular rejection (ACR) or cyclosporine (CyA) toxicity, clinical and laboratory data from the day of the biopsy were reviewed to determine their diagnostic value. Results. One biopsy specimen was inadequate for definitive interpretation. The biopsy findings resulted in a change in patient management in 22 (41.5%) of the remaining 53 cases (change group). The incidence of altered patient management was 38.7% in biopsy specimens taken in the first month, 55.6% between 1 and 12 months, and 38.5% after 1 year posttransplantation. A change in management was required in 2 of 2 patients with chronic allograft dysfunction, in 44.4% of the 45 patients with acute allograft dysfunction, and in none of the patients with delayed graft function (n=6), Within the first week of treatment 19 of 22 (86.4%) in the change group and 25 of 31 (80.6%) in the no change group had a positive response to therapy. The 1-year allograft survival rate was also similar between the two groups. None of the clinical and laboratory data was useful in distinguishing ACR from CyA toxicity. Conclusions. Renal allograft biopsy findings alter patient management recommendations in approximately 40% of patients in whom a presumptive diagnosis had been made on the basis of clinical and laboratory findings. Patients who had a change in patient management because of biopsy findings demonstrated a response to therapy and allograft survival similar to those of patients who had no alteration in management plan after the biopsy. C1 Massachusetts Gen Hosp, Renal Unit, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Dept Pathol, Box MZ70, Boston, MA 02114 USA. NR 18 TC 31 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 1999 VL 67 IS 5 BP 737 EP 741 DI 10.1097/00007890-199903150-00016 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 178NU UT WOS:000079273300016 PM 10096531 ER PT J AU Alexander-Bridges, IM Cahill, C Ogg, S Ruykun, G Ayruch, J Nasrin, N Tziyion, G AF Alexander-Bridges, IM Cahill, C Ogg, S Ruykun, G Ayruch, J Nasrin, N Tziyion, G TI DAF-16 regulates the transcription of the insulin sensitive gene insulin-like growth factor binding protein (IGFBP)-1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A77 EP A77 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300444 ER PT J AU Bensussan, A Agrawal, S Marquet, J Freeman, G Tawab, A Boumsell, L AF Bensussan, A Agrawal, S Marquet, J Freeman, G Tawab, A Boumsell, L TI A novel NK cell receptor costimulates proliferation of activated human T cells via MHC class I ligation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Hop Henri Mondor, Fac Med, INSERM, U448, F-94010 Creteil, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Bensussan, Armand/E-5434-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A307 EP A307 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301777 ER PT J AU Carter, EA Tompkins, RG Fischman, AJ AF Carter, EA Tompkins, RG Fischman, AJ TI Burn induced insulin resistance in rats is associated with increased skin and intestinal replication and apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A221 EP A221 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301274 ER PT J AU Carter, EA Hillier, S Tompkins, RG Fischman, AJ AF Carter, EA Hillier, S Tompkins, RG Fischman, AJ TI Clearance of radiolabeled insulin in the burned rat SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A221 EP A221 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301273 ER PT J AU Durante, W Peyton, KJ Schafer, AI AF Durante, W Peyton, KJ Schafer, AI TI Platelet-derived growth factor induces heme oxygenase-1 gene expression and carbon monoxide formation by vascular smooth muscle cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VAMC, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A37 EP A37 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300214 ER PT J AU Elgadi, KM Meguid, RA Souba, WW Abcouwer, SF AF Elgadi, KM Meguid, RA Souba, WW Abcouwer, SF TI Cloning and analysis of unique human glutaminase isoforms generated by tissuespecific alternative splicing SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Oncol Res Labs,Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A566 EP A566 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303264 ER PT J AU Fukumura, D Gohongi, T Ang, J Huang, PL Jain, RK AF Fukumura, D Gohongi, T Ang, J Huang, PL Jain, RK TI Role of type II and IIINOS in VEGF-induced angiogenesis and vascular permeability. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A9 EP A9 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300050 ER PT J AU Fukumura, D Gohongi, T Ohtaka, K Stoll, B Chen, Y Seed, B Jain, RK AF Fukumura, D Gohongi, T Ohtaka, K Stoll, B Chen, Y Seed, B Jain, RK TI Regulation of VEGF promoter activity in tumors by tissue oxygen and pH levels SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A9 EP A9 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300052 ER PT J AU Garnovskaya, M Mukhin, Y Raymond, J AF Garnovskaya, M Mukhin, Y Raymond, J TI Angiotensin II and serotonin induce the phosphorylation of serine 727 of STAT3 in vascular smooth muscle cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A468 EP A468 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302698 ER PT J AU Gazdag, AC Dumke, CL Kahn, CR Cartee, GD AF Gazdag, AC Dumke, CL Kahn, CR Cartee, GD TI Insulin sensitizing effect of calorie restriction on skeletal muscle glucose transport is undiminished in IRS-1 deficient mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Wisconsin, Biodynam Lab, Madison, WI 53706 USA. Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A54 EP A54 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300310 ER PT J AU Hansen-Algenstaedt, N Fukumura, D Stoll, B Padera, T Hicklin, DJ Jain, RK AF Hansen-Algenstaedt, N Fukumura, D Stoll, B Padera, T Hicklin, DJ Jain, RK TI Oxygen levels during antivascular, neoplastic and combined therapy SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Imclone Syst, New York, NY 10014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A26 EP A26 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300149 ER PT J AU Hansen-Algenstaedt, N Fukumura, D Stoll, B Hicklin, DJ Jain, RK AF Hansen-Algenstaedt, N Fukumura, D Stoll, B Hicklin, DJ Jain, RK TI Second wave of angiogenesis during anti- KDR/FLK-I antibody therapy SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Imclone Syst, New York, NY 10014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A2 EP A2 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300013 ER PT J AU Hansen-Algenstaedt, P Antonetti, DA Greten, H Kahn, CR AF Hansen-Algenstaedt, P Antonetti, DA Greten, H Kahn, CR TI Differential signaling by alternatively spliced form of p85, the subunit of PI 3-kinase SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Univ Klin Eppendorf, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A76 EP A76 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300437 ER PT J AU Herak-Kramberger, CM Breton, S Brown, D Hersak, E Sabolic, I AF Herak-Kramberger, CM Breton, S Brown, D Hersak, E Sabolic, I TI Localization of vacuolar proton-ATPase (V-ATpase) along the male reproductive tract in rat SO FASEB JOURNAL LA English DT Meeting Abstract C1 IMI, Zagreb 10001, Croatia. Massachusetts Gen Hosp, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A398 EP A398 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302297 ER PT J AU Hines, CK Walker, LL Chen, JF Jacobson, MA Fink, JS Scharzchild, MA Salvatore, CA Marquardt, DL AF Hines, CK Walker, LL Chen, JF Jacobson, MA Fink, JS Scharzchild, MA Salvatore, CA Marquardt, DL TI Effects of A(2a) and A(3) adenosine receptor ablation on mouse mast cell function SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Merck Res Labs, Dept Pharmacol, W Point, PA 19486 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A324 EP A324 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301875 ER PT J AU Husain, Z Dubey, DP Levitan, E Alper, CA Yunis, EJ AF Husain, Z Dubey, DP Levitan, E Alper, CA Yunis, EJ TI Natural killer receptor(NKR) gene expression in single cells: Association of zygosity and NKR expression in human NK cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A308 EP A308 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301782 ER PT J AU Kling, DE Schnitzer, JJ AF Kling, DE Schnitzer, JJ TI Decreased MEK1 enzymatic activity in prenatal rat lungs with congenital diaphragmatic hernia. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A354 EP A354 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302046 ER PT J AU Koenig, GC Melder, RJ Jain, RK AF Koenig, GC Melder, RJ Jain, RK TI Signaling mechanisms used by bFGF in downregulating cell adhesion molecule expression. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A36 EP A36 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300207 ER PT J AU Koike, G Grigor, MR Harris, EL Jacob, HJ Sassard, J AF Koike, G Grigor, MR Harris, EL Jacob, HJ Sassard, J TI Implication for genetic studies of human complex diseases from results obtained in genetic hypertension of rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Otago, Dunedin, New Zealand. Fac Pharm Lyon, Lyon, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A380 EP A380 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302193 ER PT J AU Lantz, CS Song, CH Dranoff, G Galli, SJ AF Lantz, CS Song, CH Dranoff, G Galli, SJ TI Interleukin-3 (IL-3) is required for blood basophilia, but not for increased basophil IL-4 production, in response to parasite infection in mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A325 EP A325 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301882 ER PT J AU Lichtenbeld, HC Leak, LV Munn, LL Jain, RK AF Lichtenbeld, HC Leak, LV Munn, LL Jain, RK TI Lymphangiogenesis in tumors SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Howard Univ, Dept Anat, Washington, DC 20059 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A6 EP A6 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300033 ER PT J AU Melder, RJ Kurnick, JT Boyle, L Jain, RK AF Melder, RJ Kurnick, JT Boyle, L Jain, RK TI T lymphocyte recruitment in human tumor xenografts varies with tumor type SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A302 EP A302 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301746 ER PT J AU Mukhin, Y Collinsworth, G Fitzgibbon, W Ploth, D Raymond, J Garnovskaya, M AF Mukhin, Y Collinsworth, G Fitzgibbon, W Ploth, D Raymond, J Garnovskaya, M TI Bradykinin B-2 receptor activation increases Na+/H+ exchange in mIMCD-3 cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Ralph H Johnson VAMC, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A135 EP A135 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300778 ER PT J AU Munn, LL Patan, S Tanda, A Roberge, S Jones, RC Jain, RK AF Munn, LL Patan, S Tanda, A Roberge, S Jones, RC Jain, RK TI Structural basis of angiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A6 EP A6 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300036 ER PT J AU Patan, S Tanda, S Roberge, S Jones, RC Jain, RK Munn, LL AF Patan, S Tanda, S Roberge, S Jones, RC Jain, RK Munn, LL TI Structural basis of angiogenesis in wound healing and tumor growth SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A185 EP A185 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301070 ER PT J AU Pena, AA Williams, MD Van Remmen, H Richardson, A AF Pena, AA Williams, MD Van Remmen, H Richardson, A TI Increased oxidative damage is correlated to altered mitochondrial enzyme activities in skeletal muscle. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A413 EP A413 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302383 ER PT J AU Schuchert, MJ Wright, RD Colson, YL AF Schuchert, MJ Wright, RD Colson, YL TI Facilitating cell surface markers parallel early T cell development. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15261 USA. Dana Farber Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A615 EP A615 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303547 ER PT J AU Simbulan-Rosenthal, C Rosenthal, D Luo, R Kaelin, W Smulson, M AF Simbulan-Rosenthal, C Rosenthal, D Luo, R Kaelin, W Smulson, M TI Poly(ADP-ribose) polymerase (PARP) upregulates E2F-1 promoter activity during early S-phase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Georgetown Univ, Sch Med, Washington, DC 20007 USA. Dana Farber Canc Inst, Boston, MA 02146 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A351 EP A351 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302033 ER PT J AU Stoll, BR Fukumura, D Hansen-Algenstaedt, N Jain, RK AF Stoll, BR Fukumura, D Hansen-Algenstaedt, N Jain, RK TI Oxygen consumption and HIF-1 alpha expression in three rot rhabdomyosarcoma cell lines SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A6 EP A6 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300035 ER PT J AU Vigny, JS Beaudoin, AR Robson, SC Lemmens, R AF Vigny, JS Beaudoin, AR Robson, SC Lemmens, R TI Characterization of a novel ATP diphosphohydrolase/CD39-like protein. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. Limburgs Univ Ctr, Diepenbeek, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A234 EP A234 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301348 ER PT J AU Yu, YM Castillo, L Lyons, J Rauh-Pfeiffer, A Lu, XM Ajami, A Young, VR AF Yu, YM Castillo, L Lyons, J Rauh-Pfeiffer, A Lu, XM Ajami, A Young, VR TI Fractional synthesis rates of glutathione in healthy adults. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Shriners Burns Hosp, Boston, MA USA. MIT, Cambridge, MA 02139 USA. MassTrace, Woburn, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A566 EP A566 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303260 ER PT J AU Yuan, J Munn, LL Jain, RK AF Yuan, J Munn, LL Jain, RK TI The effects of VEGF on human umbilical vein endothelial cell migration and permeability. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 1 Z9 1 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A2 EP A2 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300011 ER PT J AU Marsischky, GT Lee, S Griffith, J Kolodner, RD AF Marsischky, GT Lee, S Griffith, J Kolodner, RD TI Saccharomyces cerevisiae MSH2/6 complex interacts with Holliday junctions and facilitates their cleavage by phage resolution enzymes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MISMATCH REPAIR SYSTEM; DNA-BASE PAIRS; GENETIC-RECOMBINATION; CROSSING-OVER; MUTS HOMOLOG; HOMEOLOGOUS RECOMBINATION; DUPLEX OLIGONUCLEOTIDES; SPECIFICALLY BINDS; ESCHERICHIA-COLI; PROTEIN AB Genetic and biochemical studies have indicated that mismatch repair proteins can interact with recombination intermediates. In this study, gel shift assays and electron microscopic analysis were used to show that the Saccharomyces cerevisiae MSH2/6 complex binds to Holliday junctions and has an affinity and specificity for them that is at least as high as it has as for mispaired bases. Under equilibrium binding conditions, the MSH2/6 complex had a K-d of binding to Holliday junctions of 0.5 nm. The MSH2/6 complex enhanced the cleavage of Holliday junctions by T4 endonuclease VII and T7 endonuclease I. This is consistent with the view that the MSH2/6 complex can function in both mismatch repair and the resolution of recombination intermediates as predicted by genetic studies. C1 Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Ctr Canc, La Jolla, CA 92093 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Charles A Dana Div Human Canc Genet, Boston, MA 02115 USA. Univ N Carolina, Lineberger Comprehens Canc Res Ctr, Chapel Hill, NC 27599 USA. RP Kolodner, RD (reprint author), Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, Dept Med, CMME-3080,9500 Gilman Dr, La Jolla, CA 92093 USA. FU NIGMS NIH HHS [GM50006, GM31819] NR 46 TC 48 Z9 50 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 1999 VL 274 IS 11 BP 7200 EP 7206 DI 10.1074/jbc.274.11.7200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400053 PM 10066781 ER PT J AU Gunn, TM Miller, KA He, L Hyman, RV Davis, RW Azarani, A Schlossman, SF Duke-Cohan, JS Barsh, GS AF Gunn, TM Miller, KA He, L Hyman, RV Davis, RW Azarani, A Schlossman, SF Duke-Cohan, JS Barsh, GS TI The mouse mahogany locus encodes a transmembrane form of human attractin SO NATURE LA English DT Article ID ALPHA-MSH; IN-VITRO; IV CD26; AGOUTI; PROTEIN; RECEPTORS; YELLOW; MICE; ANTAGONISM; MUTATIONS AB Agouti protein and agouti-related protein are homologous paracrine signalling molecules that normally regulate hair colour and body weight, respectively, by antagonizing signalling through melanocortin receptors(1-7). Expression of Agouti is normally limited to the skin, but rare alleles from which Agouti is expressed ubiquitously, such as lethal yellow; have pleiotropic effects that include a yellow coat, obesity, increased linear growth, and immune defects(8-11). The mahogany (mg) mutation suppresses the effects of lethal yellow on pigmentation and body weight, and results of our previous genetic studies place mg downstream of transcription of Agouti but upstream of melanocortin receptors(12). Here we use positional cloning to identify a candidate gene for mahogany, Mgca. The predicted protein encoded by Mgca is a 1,428-amino-acid, single-transmembrane-domain protein that is expressed in many tissues, including pigment cells and the hypothalamus. The extracellular domain of the Mgca protein is the orthologue of human attractin, a circulating molecule produced by activated T cells that has been implicated in immune-cell interactions(13,14). These observations provide new insight into the regulation of energy metabolism and indicate a molecular basis for crosstalk between melanocortin-receptor signalling and immune function. C1 Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Stanford DNA Sequencing & Technol Ctr, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RP Barsh, GS (reprint author), Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. OI Gunn, Teresa/0000-0003-2688-6420; Duke-Cohan, Jonathan/0000-0002-9478-9609 NR 29 TC 154 Z9 161 U1 2 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 11 PY 1999 VL 398 IS 6723 BP 152 EP 156 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 176DG UT WOS:000079135200045 PM 10086356 ER PT J AU Walsh, TJ Finberg, RW Arndt, C Hiemenz, J Schwartz, C Bodensteiner, D Pappas, P Seibel, N Greenberg, RN Dummer, S Schuster, M Holcenberg, JS AF Walsh, TJ Finberg, RW Arndt, C Hiemenz, J Schwartz, C Bodensteiner, D Pappas, P Seibel, N Greenberg, RN Dummer, S Schuster, M Holcenberg, JS CA Natl Inst Allergy Infect Dis Mycoses Study Grp TI Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; RISK-FACTORS; TOXICITY; AMBISOME; MANAGEMENT; INFUSION; GRANULOCYTOPENIA; EXPERIENCE; EFFICACY AB Background In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity. Methods We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy. Results The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P = 0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P<0.001). Conclusions Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity. (N Engl J Med 1999;340:764-71.) (C)1999, Massachusetts Medical Society. C1 NCI, Div Clin Sci, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Dept Pediat, Sect Pediat Hematol Oncol, Rochester, MN 55905 USA. H Lee Moffitt Canc Ctr, Div Bone Marrow Transplantat, Tampa, FL USA. Johns Hopkins Med Inst, Div Pediat Hematol Oncol, Baltimore, MD 21205 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Univ Alabama, Div Infect Dis, Birmingham, AL USA. Childrens Hosp, Natl Med Ctr, Div Hematol Oncol, Washington, DC 20010 USA. Vanderbilt Univ, Div Infect Dis, Nashville, TN USA. Hosp Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. RP Walsh, TJ (reprint author), NCI, Div Clin Sci, Bldg 10,Rm 13N-240, Bethesda, MD 20892 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [N01-AI-65296] NR 32 TC 723 Z9 758 U1 1 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 1999 VL 340 IS 10 BP 764 EP 771 DI 10.1056/NEJM199903113401004 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 174KJ UT WOS:000079034100004 PM 10072411 ER PT J AU Syngal, S Kaptain, S O'Neill, MJ Isselbacher, KJ Sober, AJ Chung, DC Haluska, FG AF Syngal, S Kaptain, S O'Neill, MJ Isselbacher, KJ Sober, AJ Chung, DC Haluska, FG TI A 50-year-old woman with severe diarrhea during radiation treatment for resected metastatic melanoma Cutaneous melanoma metastasized to the gastrointestinal tract, with protein-losing enteropathy. Adrenal cortical adenoma. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MALIGNANT-MELANOMA; PROGNOSTIC INDICATORS; SECONDARY; LYMPHOMA; CANCER; RISK C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Syngal, S (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 53 TC 2 Z9 2 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 1999 VL 340 IS 10 BP 789 EP 796 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 174KJ UT WOS:000079034100008 ER PT J AU Ince, N Wands, JR AF Ince, N Wands, JR TI The increasing incidence of hepatocellular carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HEPATITIS-C; TAIWAN; VIRUS C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Ince, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NR 12 TC 136 Z9 138 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 1999 VL 340 IS 10 BP 798 EP 799 DI 10.1056/NEJM199903113401009 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 174KJ UT WOS:000079034100009 PM 10072416 ER PT J AU Benson, RR FitzGerald, DB LeSueur, LL Kennedy, DN Kwong, KK Buchbinder, BR Davis, TL Weisskoff, RM Talavage, TM Logan, WJ Cosgrove, GR Belliveau, JW Rosen, BR AF Benson, RR FitzGerald, DB LeSueur, LL Kennedy, DN Kwong, KK Buchbinder, BR Davis, TL Weisskoff, RM Talavage, TM Logan, WJ Cosgrove, GR Belliveau, JW Rosen, BR TI Language dominance determined by whole brain functional MRI in patients with brain lesions SO NEUROLOGY LA English DT Article ID WADA TEST; LOCALIZATION; STIMULATION; HEMISPHERE; ANATOMY; STROKE AB Background: Functional MRI (fMRI) is of potential value in determining hemisphere dominance for language in epileptic patients. Objective: To develop and validate an fMRI-based method of determining language dominance for patients with a nide range of potentially operable brain lesions in addition to epilepsy. Methods: Initially, a within-subjects design was used with 19 healthy volunteers (11 strongly right-handed, 8 left-handed) to determine the relative lateralizing usefulness of three different language tasks in fMRI. An automated, hemispheric analysis of laterality was used to analyze whole brain fMRI data sets. To evaluate the clinical usefulness of this method, we compared fMRI-determined laterality with laterality determined by Wada testing or electrocortical stimulation mapping, or both, in 23 consecutive patients undergoing presurgical evaluation of language dominance. Results: Only the verb generation task. was reliably lateralizing, fMRI, using the verb generation task and an automated hemispheric analysis method, was concordant with invasive measures in 22 of 23 patients (12 Wada, 11 cortical stimulation). For the single patient who was discordant, in whom a tumor involved one-third of the left hemisphere, fMRI became concordant when the tumor and its reflection in the right hemisphere were excluded from laterality analysis. No significant negative correlation was obtained between lesion size and strength of laterality for the patients with lesions involving the dominant hemisphere. Conclusion: This fMRI method shows potential for evaluating language dominance in patients with a variety of brain lesions. C1 Univ Connecticut, Ctr Hlth, Dept Neurol, Farmington, CT 06030 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH NMR Ctr,Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Morphometr Anal,Dept Neurol, Boston, MA USA. Purdue Univ, Dept Elect & Comp Engn, W Lafayette, IN 47907 USA. Hosp Sick Children, Div Neurol, Toronto, ON M5G 1X8, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Charlestown, MA USA. Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. RP Benson, RR (reprint author), Univ Connecticut, Ctr Hlth, Dept Neurol, 263 Farmington Ave, Farmington, CT 06030 USA. RI Kennedy, David/H-3627-2012 FU NCI NIH HHS [5T32CA09502]; NHLBI NIH HHS [T35-HL07841-01A1]; NIMH NIH HHS [R01-MH50054] NR 40 TC 243 Z9 251 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 10 PY 1999 VL 52 IS 4 BP 798 EP 809 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 175ZR UT WOS:000079126400025 PM 10078731 ER PT J AU Shafqat, S Hedley-Whyte, ET Henson, JW AF Shafqat, S Hedley-Whyte, ET Henson, JW TI Age-dependent rate of anaplastic transformation in low-grade astrocytoma SO NEUROLOGY LA English DT Article ID SURVIVAL; GLIOMAS AB Age and histologic grade are interrelated characteristics of diffuse fibrillary astrocytomas, because the peak age incidence rises with increasing grade. The relationship between age and grade may be explained if age determines the rate of anaplastic progression in astrocytomas. The authors tested this hypothesis by determining the interval between diagnosis of low-grade astrocytoma and progression to high-grade astrocytoma in patients of various ages. A two-way scatterplot of age at initial diagnosis versus interval to anaplastic progression demonstrated a strong negative correlation (n = 24; Pearson correlation coefficient = -0.83; Spearman correlation coefficient = -0.79; p < 0.001 for both values). It was concluded that the rate of anaplastic progression in low-grade astrocytoma is directly correlated with patient age. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, 100 Blossom St, Boston, MA 02114 USA. NR 10 TC 45 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 10 PY 1999 VL 52 IS 4 BP 867 EP 869 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 175ZR UT WOS:000079126400039 PM 10078745 ER PT J AU Whooley, MA Kip, KE Cauley, JA Ensrud, KE Nevitt, MC Browner, WS AF Whooley, MA Kip, KE Cauley, JA Ensrud, KE Nevitt, MC Browner, WS CA Study Osteoporotic Fractures Res Grp TI Depression, falls, and risk of fracture in older women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BONE-MINERAL DENSITY; HIP FRACTURE; OSTEOPOROTIC FRACTURES; NURSING-HOME; LATER LIFE; DISABILITY; SYMPTOMS; OUTCOMES; MASS; INDEX AB Background: Previous studies have suggested that depression is associated with falls and with low bone density, but it is not known whether depression leads to an increased risk of fracture. Subjects and Methods: We conducted a prospective cohort study in elderly white women who were recruited from population-based listings in the United States. At a second visit (1988-1990), 7414 participants completed the 15-item Geriatric Depression Scale and were considered depressed if they reported 6 or more symptoms of depression. We measured bone mineral density (BMD) in the spine and hip using dual energy x-ray absorptiometry at the second visit, and asked participants about incident falls (yes/no) at 4 follow-up visits. Nonvertebral fractures were ascertained for an average of 6 years following the depression measure, and verified radiologically. We determined incident vertebral fractures by comparing lateral spine films obtained at the first visit (1986-1988) with repeat films obtained an average of 3.7 years later (1991-1992). Results: The prevalence of depression (Geriatric Depression Scale score greater than or equal to 6) was 6.3% (467/7414). We found no difference in mean BMD of the hip and lumbar spine in women with depression compared with those without depression. Women with depression were more likely to experience subsequent falls than women without depression (70% vs 59%; age-adjusted odds ratio [OR], 1.6; 95% confidence interval [CI], 1.3-1.9; P < .001), an association that persisted after adjusting for potential confounding variables (OR, 1.4; 95% CI, 1.1-1.8; P = .004). Women with depression had a 40% (age-adjusted hazard ratio [HR], 1.4; 95% CI, 1.2-1.7; P < .001) increased rate of nonvertebral fracture (124 fractures in 3805 woman-years of follow-up) compared with women without depression (1367 fractures in 59 503 woman-years of followup). This association remained strong after adjusting for potential confounding variables, including medication use and neuromuscular function (HR, 1.3; 95% CI, 1.1-1.6; P = .008). Further adjustment for subsequent falls appeared to explain part of this association (HR, 1.2; 95% CI, 1.0-1.5; P = .06). Women with depression were also more likely to suffer vertebral fractures than women without depression, adjusting for history of vertebral fracture, history of falling, arthritis, diabetes, steroid use, estrogen use, supplemental calcium use, cognitive function, and hip BMD (OR, 2.1; 95% CI, 1.4-3.2; P < .001). Conclusions: Depression is a significant risk factor for fracture in older women. The greater frequency of falls among individuals with depression partially explains this finding. Other mechanisms responsible for the association between depression and fracture remain to be determined. C1 San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. RP Whooley, MA (reprint author), San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, 4150 Clement St,111A1, San Francisco, CA 94121 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [AG05394, AG05407]; NIAMS NIH HHS [AR35582] NR 49 TC 201 Z9 209 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 8 PY 1999 VL 159 IS 5 BP 484 EP 490 DI 10.1001/archinte.159.5.484 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 172FK UT WOS:000078912600010 PM 10074957 ER PT J AU Lee, L Klee, SK Evangelista, M Boone, C Pellman, D AF Lee, L Klee, SK Evangelista, M Boone, C Pellman, D TI Control of mitotic spindle position by the Saccharomyces cerevisiae formin Bni1p SO JOURNAL OF CELL BIOLOGY LA English DT Article DE mitotic spindle apparatus; cell division; microtubule; actin; Saccharomyces cerevisiae ID BUD-SITE SELECTION; LIMB DEFORMITY GENE; GTP-BINDING PROTEIN; BUDDING YEAST; CELL POLARITY; ACTIN CYTOSKELETON; CAENORHABDITIS-ELEGANS; NUCLEAR MIGRATION; MORPHOGENESIS; CYTOKINESIS AB Alignment of the mitotic spindle with the axis of cell division is an essential process in Saccharomyces cerevisiae that is mediated by interactions between cytoplasmic microtubules and the cell cortex. We found that a cortical protein, the yeast formin Bni1p, was required for spindle orientation. Two striking abnormalities were observed in bni1 Delta cells, First, the initial movement of the spindle pole body (SPB) toward the emerging bud was defective, This phenotype is similar to that previously observed in cells lacking the kinesin Kip3p and, in fact, BNI1 and KIP3 were found to be in the same genetic pathway. Second, abnormal pulling interactions between microtubules and the cortex appeared to cause preanaphase spindles in bni1 Delta cells to transit back and forth between the mother and the bud. We therefore propose that Bni1p may localize or alter the function of cortical microtubule-binding sites in the bud. Additionally, we present evidence that other bipolar bud site determinants together with cortical actin are also required for spindle orientation. C1 Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat Hematol, Boston, MA 02115 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Univ Stuttgart, Inst Biochem, D-70569 Stuttgart, Germany. Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada. RP Dana Farber Canc Inst, Room M621A,44 Binney St, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu FU NIGMS NIH HHS [GM55772] NR 73 TC 126 Z9 128 U1 0 U2 2 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 MAR 8 PY 1999 VL 144 IS 5 BP 947 EP 961 DI 10.1083/jcb.144.5.947 PG 15 WC Cell Biology SC Cell Biology GA 180GE UT WOS:000079377100013 PM 10085293 ER PT J AU Van Koughnet, K Smirnova, O Hyman, SE Borsook, D AF Van Koughnet, K Smirnova, O Hyman, SE Borsook, D TI Proenkephalin transgene regulation in the paraventricular nucleus of the hypothalamus by lipopolysaccharide and interleukin-1 beta SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE phosphocyclic amino-3-hydroxy-5-methyl-4-isoxazole-propionate response element-binding protein; naltrexone; stress; mice ID CORTICOTROPIN-RELEASING HORMONE; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA EXPRESSION; PARVOCELLULAR NEUROSECRETORY NEURONS; PITUITARY-ADRENOCORTICAL ACTIVITY; GALACTOSIDASE FUSION GENE; IN-SITU HYBRIDIZATION; IMMEDIATE-EARLY GENES; RAT-BRAIN; SUPRAOPTIC NUCLEI AB Immunologic challenge with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta) produces a functional response within the paraventricular nucleus of the hypothalamus (PVN) and leads to changes in gene expression within PVN neurons. Regulated expression of neuropeptide genes within neurons of the PVN is a potential mechanism by which an organism can adapt to stressful challenges. Here, the authors used a transgenic mouse model in which expression of a readily measurable beta-galactosidase reporter was driven in PVN neurons by human proenkephalin regulatory sequences. This proenkephalin-beta-galactosidase transgene has been demonstrated previously to respond appropriately to a variety of stressors. It is demonstrated that expression of the proenkephalin transgene product was up-regulated significantly in a subset of PVN neurons 6 hours following intraperitoneal LPS (16-400 mu g/kg) administration, remained elevated at 12 hours, and fell below basal levels by 24 hours. A more rapid and transient pattern of transgene up-regulation in the PVN followed administration of intraperitoneal IL-1 beta (10 mu g/kg) with significant induction by 2 hours, peak levels reached by 4 hours, and a return toward basal levels by 6 hours. IL-1 beta (10-50 ng/mouse) administered intracerebroventricularly also led to up-regulation of the transgene 6 hours following infusion. Transgene expression was not up-regulated in hypothalamic slice cultures treated directly with IL-1 beta (5-10 ng/ml media). Up-regulation of transgene expression does not appear to result from local action of IL-1 beta at the level of the PVN but, rather, through as yet unidentified intermediates. The authors demonstrate phosphorylation of the cyclic amino-3-hydroxy-5-methyl-4-isoxazole-propionate response element binding protein, a transcription factor known to interact with proenkephalin regulatory sequences within the transgene, in the PVN following LPS administration. LPS induced up-regulation of the transgene was blocked by pretreatment with naltrexone, indicating an additional role for endogenous opioid systems in regulation of the PVN response to immune challenge. J. Comp. Neurol. 405:199-215, 1999. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. NINDS, Mol Plast Sect, Rockville, MD 20892 USA. Massachusetts Gen Hosp, Neural Plast Res Grp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp E, Neural Plast Res Grp, Bldg 149,13th St,CNY4, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA0956501] NR 119 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 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 8 PY 1999 VL 405 IS 2 BP 199 EP 215 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 163NM UT WOS:000078411900005 PM 10023810 ER PT J AU Nathan, DG Weatherall, DJ AF Nathan, DG Weatherall, DJ TI Academia and industry: lessons from the unfortunate events in Toronto SO LANCET LA English DT Editorial Material ID THALASSEMIA; THERAPY C1 Dana Farber Inst Canc Res, Boston, MA 02115 USA. Univ Oxford, Inst Mol Med, Oxford OX3 9DS, England. RP Nathan, DG (reprint author), Dana Farber Inst Canc Res, Boston, MA 02115 USA. NR 9 TC 26 Z9 26 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 6 PY 1999 VL 353 IS 9155 BP 771 EP 772 DI 10.1016/S0140-6736(99)00072-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 175JC UT WOS:000079089100006 PM 10459956 ER PT J AU Otto, LR Boriack, RL Marsh, DJ Kum, JB Eng, C Burlina, AB Bennett, MJ AF Otto, LR Boriack, RL Marsh, DJ Kum, JB Eng, C Burlina, AB Bennett, MJ TI Long-chain L 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency does not appear to be the primary cause of lipid myopathy in patients with Bannayan-Riley-Ruvalcaba syndrome (ERRS) SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Bannayan-Riley-Ruvalcaba syndrome; Bannayan-Zonana syndrome; Ruvalcaba-Riley-Smith syndrome; Ruvalcaba-Myhre-Smith syndrome; carnitine deficiency; myopathy; mitochondria ID ACID BETA-OXIDATION; GERMLINE MUTATIONS; PTEN; PROTEIN; GENE; IDENTIFICATION; BREAST; CANCER; LOCUS AB In order to test the hypothesis that long-chain L 3-hydroxyacyl-coenzyme A dehydrogenase (LCHAD) deficiency is associated with the lipid myopathy and muscle carnitine deficiency observed in Bannayan-Riley-Ruvalcaba syndrome (ERRS), we studied the enzyme activity in cultured skin fibroblasts from three generations of a family with a clear dominant inheritance of ERRS. Enzyme activities were normal while the germline PTEN missense mutation P246L segregated with ERRS in this family. No PTEN mutations were identified in the original patient with ERRS and LCHAD deficiency. These data suggest that the previously reported case of LCHAD and ERRS either represents the coincidental concurrence of two rare genetic events or that a gene other than PTEN is related to LCHAD and ERRS, (C) 1999 Wiley-Liss, Inc. C1 Childrens Med Ctr, Dept Pathol, Dallas, TX 75235 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Translat Res Lab, Boston, MA 02115 USA. Univ Padua, Dept Pediat, Padua, Italy. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX USA. RP Bennett, MJ (reprint author), Childrens Med Ctr, Dept Pathol, 1985 Motor St, Dallas, TX 75235 USA. RI Marsh, Deborah/I-1491-2014 OI Marsh, Deborah/0000-0001-5899-4931 FU Telethon [949] NR 16 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 5 PY 1999 VL 83 IS 1 BP 3 EP 5 DI 10.1002/(SICI)1096-8628(19990305)83:1<3::AID-AJMG2>3.0.CO;2-K PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 171TC UT WOS:000078879300002 PM 10076877 ER PT J AU Farzan, M Mirzabekov, T Kolchinsky, P Wyatt, R Cayabyab, M Gerard, NP Gerard, C Sodroski, J Choe, H AF Farzan, M Mirzabekov, T Kolchinsky, P Wyatt, R Cayabyab, M Gerard, NP Gerard, C Sodroski, J Choe, H TI Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry SO CELL LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR CCR5; 7-TRANSMEMBRANE SEGMENT RECEPTORS; HEPARAN-SULFATE; MOLECULAR-CLONING; FUSION COFACTOR; TROPIC HIV-1; IDENTIFICATION; MIP-1-ALPHA; MIP-1-BETA AB Chemokine receptors and related seven-transmembrane-segment (7TMS) receptors serve as coreceptors for entry of human and simian immunodeficiency viruses (HIV-1, HIV-2, and SIV) into target cells. Each of these otherwise diverse coreceptors contains an N-terminal region that is acidic and tyrosine rich. Here, we show that the chemokine receptor CCR5, a principal HIV-1 coreceptor, is posttranslationally modified by O-linked glycosylation and by sulfation of its N-terminal tyrosines. Sulfated tyrosines contribute to the binding of CCR5 to MIP-1 alpha, MIP-1 beta, and HIV-1 gp120/CD4 complexes and to the ability of HIV-1 to enter cells expressing CCR5 and CD4. CXCR4, another important HIV-1 coreceptor, is also sulfated. Tyrosine sulfation may contribute to the natural function of many 7TMS receptors and may be a modification common to primate immunodeficiency virus coreceptors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Childrens Hosp, Ina Sue Perlmutter Lab, Boston, MA 02115 USA. Beth Israel Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Hosp, Dept Pediat, Boston, MA 02115 USA. RP Farzan, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Human Retrovirol, 44 Binney St, Boston, MA 02115 USA. EM farzan@mbcrr.harvard.edu FU NIAID NIH HHS [AI 24755, AI 28691, AI 41851] NR 56 TC 479 Z9 497 U1 5 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 5 PY 1999 VL 96 IS 5 BP 667 EP 676 DI 10.1016/S0092-8674(00)80577-2 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 174TB UT WOS:000079050100010 PM 10089882 ER PT J AU Westphal, CH Muller, L Zhou, A Zhu, XR Bonner-Weir, S Schambelan, M Steiner, DF Lindberg, I Leder, P AF Westphal, CH Muller, L Zhou, A Zhu, XR Bonner-Weir, S Schambelan, M Steiner, DF Lindberg, I Leder, P TI The neuroendocrine protein 7B2 is required for peptide hormone processing in vivo and provides a novel mechanism for pituitary Cushing's disease SO CELL LA English DT Article ID PROHORMONE CONVERTASE PC2; DOPAMINERGIC REGULATION; PROPROTEIN CONVERTASES; GENE-EXPRESSION; POLYPEPTIDE 7B2; TRANSGENIC MICE; RAT PITUITARY; GROWTH-FACTOR; CELLS; PROOPIOMELANOCORTIN AB The neuroendocrine protein 7B2 has been implicated in activation of prohormone convertase 2 (PC2), an important neuroendocrine precursor processing endoprotease. To test this hypothesis, we created a null mutation in 7B2 employing a novel transposon-facilitated technique and compared the phenotypes of 7B2 and PC2 nulls. 7B2 null mice have no demonstrable PC2 activity, are deficient in processing islet hormones, and display hypoglycemia, hyperproinsulinemia, and hypoglucagonemia. In contrast to the PC2 null phenotype, these mice show markedly elevated circulating ACTH and corticosterone levels, with adrenocortical expansion. They die before 9 weeks of severe Cushing's syndrome arising from pituitary intermediate lobe ACTH hypersecretion. We conclude that 7B2 is indeed required for activation of PC2 in vivo but has additional important functions in regulating pituitary hormone secretion. C1 Louisiana State Univ, Med Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. Univ Chicago, Dept Biochem, Chicago, IL 60637 USA. Joslin Diabet Ctr 535, Boston, MA 02215 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Lindberg, I (reprint author), Louisiana State Univ, Med Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. RI muller, laurent/S-1990-2016 FU NIDA NIH HHS [DA00204, DA05084]; NIDDK NIH HHS [R01 DK049703, DK49703] NR 55 TC 140 Z9 143 U1 2 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 5 PY 1999 VL 96 IS 5 BP 689 EP 700 DI 10.1016/S0092-8674(00)80579-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 174TB UT WOS:000079050100012 PM 10089884 ER PT J AU Rudolph, KL Chang, S Lee, HW Blasco, M Gottlieb, GJ Greider, C DePinho, RA AF Rudolph, KL Chang, S Lee, HW Blasco, M Gottlieb, GJ Greider, C DePinho, RA TI Longevity, stress response, and cancer in aging telomerase-deficient mice SO CELL LA English DT Article ID LIFE-SPAN; CELLULAR SENESCENCE; SACCHAROMYCES-CEREVISIAE; REPLICATIVE SENESCENCE; HUMAN FIBROBLASTS; HUMAN-LYMPHOCYTES; MOUSE CELLS; LENGTH; AGE; MORPHOLOGY AB Telomere maintenance is thought to play a role in signaling cellular senescence; however, a link with organismal aging processes has not been established. The telomerase null mouse provides an opportunity to understand the effects associated with critical telomere shortening at the organismal level. We studied a variety of physiological processes in an aging cohort of mTR(-/-) mice. Loss of telomere function did not elicit a full spectrum of classical pathophysiological symptoms of aging. However, age-dependent telomere shortening and accompanying genetic instability were associated with shortened life span as well as a reduced capacity to respond to stresses such as wound healing and hematopoietic ablation. In addition, we found an increased incidence of spontaneous malignancies. These findings demonstrate a critical role for telomere length in the overall fitness, reserve, and well being of the aging organism. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02110 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02110 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02110 USA. Quest diagnost Inc, Anat Pathol, Teterboro, NJ 07608 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Sungkyunkwan Univ, Sch Med, Ctr Mol Med, Samsung Biomed Res Inst, Seoul 135230, South Korea. Natl Biotechnol Ctr, Dept Immunol & Oncol, E-28049 Madrid, Spain. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,M413, Boston, MA 02115 USA. RI Blasco , Maria A./M-1694-2014 OI Blasco , Maria A./0000-0002-4211-233X FU NIA NIH HHS [K08 AG001019] NR 66 TC 879 Z9 915 U1 13 U2 68 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 5 PY 1999 VL 96 IS 5 BP 701 EP 712 DI 10.1016/S0092-8674(00)80580-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 174TB UT WOS:000079050100013 PM 10089885 ER PT J AU Rogers, JT Leiter, LM McPhee, J Cahill, CM Zhan, SS Potter, H Nilsson, LNG AF Rogers, JT Leiter, LM McPhee, J Cahill, CM Zhan, SS Potter, H Nilsson, LNG TI Translation of the Alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5 '-untranslated region sequences SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; IRON-RESPONSIVE ELEMENT; FERRITIN MESSENGER-RNA; BETA-PROTEIN; APOLIPOPROTEIN-E; GENE-EXPRESSION; TRANSGENIC MICE; RAT-BRAIN; IN-VITRO; DISEASE AB The amyloid precursor protein (APP) has been associated with Alzheimer's disease (AD) because APP is processed into the beta-peptide that accumulates in amyloid plaques, and APP gene mutations can cause early onset AD. Inflammation is also associated with AD as exemplified by increased expression of interleukin-l (IL-1) in microglia in affected areas of the AD brain. Here we demonstrate that IL-1 alpha and IL-beta increase APP synthesis by up to 6-fold in primary human astrocytes and by 15-fold in human astrocytoma cells without changing the steady-state levels of APP mRNA. A 90-nucleotide sequence in the APP gene 5'-untranslated region (5'-UTR) conferred translational regulation by IL-l alpha and IL-1 beta to a chloramphenicol acetyltransferase (CAT) reporter gene. Steady-state levels of transfected APP(5'-UTR)/CAT mRNAs were unchanged, whereas both baseline and IL-l-dependent CAT protein synthesis were increased. This APP mRNA translational enhancer maps from +55 to +144 nucleotides from the 5'-cap site and is homologous to related translational control elements in the 5'-UTR of the light and and heavy ferritin genes. Enhanced translation of APP mRNA provides a mechanism by which IL-1 influences the pathogenesis of AD. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Univ S Florida, Dept Biochem & Mol Biol, Tampa, FL 33612 USA. Univ S Florida, Suncoast Gerontol Ctr, Tampa, FL 33612 USA. RP Rogers, JT (reprint author), 604 LMRC,221 Longwood Ave, Boston, MA 02115 USA. EM Rogers@calvin.bwh.harvard.edu FU ADAMHA HHS [AD09665]; NIAMS NIH HHS [AR29I32717]; PHS HHS [6872302] NR 67 TC 208 Z9 216 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 1999 VL 274 IS 10 BP 6421 EP 6431 DI 10.1074/jbc.274.10.6421 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172BQ UT WOS:000078902800056 PM 10037734 ER PT J AU Zusman, RM AF Zusman, RM TI Cardiovascular data on sildenafil citrate - Introduction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Hypertens & Vasc Med, Boston, MA 02114 USA. RP Zusman, RM (reprint author), Massachusetts Gen Hosp, Cardiac Unit, 15 Parkman St,WACC 482, Boston, MA 02114 USA. NR 0 TC 18 Z9 22 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 4 PY 1999 VL 83 IS 5A SI SI BP 1C EP 2C DI 10.1016/S0002-9149(99)00041-7 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 174YF UT WOS:000079063600001 PM 10078536 ER PT J AU Zusman, RM Morales, A Glasser, DB Osterloh, IH AF Zusman, RM Morales, A Glasser, DB Osterloh, IH TI Overall cardiovascular profile of sildenafil citrate SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TRIGGERING MYOCARDIAL-INFARCTION; NITRIC-OXIDE; SEXUAL-ACTIVITY; CORPUS CAVERNOSUM; PRESSURE; PHYSIOLOGY; MEDIATOR; DISEASE AB Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is the first in a new class of orally effective treatments for erectile dysfunction. During sexual stimulation,; the cavernous nerves release nitric oxide (NO), which induces cyclic guanosine monophosphate (cGMP) formation and smooth muscle relaxation in the corpus cavernosum. Sildenafil facilitates the erectile process during sexual stimulation by inhibiting PDE5 and thus blocking the breakdown of cGMP. Sildenafil alone can cause mean peak reductions in systolic/diastolic blood pressure of 10/7 mm Hg that are not dose related, whereas the heart rate is unchanged. Sildenafil and nitrates both increase cGMP levels in the systemic circulation but at different points along the NO-cGMP pathway. The combination is contraindicated because they synergistically potentiate vasodilation and may cause excessive reductions in blood pressure. Erectile dysfunction is a significant medical condition that shares numerous risk factors with ischemic heart disease, and hence a substantial overlap exists between these patient groups. From extensive clinical trials, the most commonly reported cardiovascular adverse events in patients treated with sildenafil were headache (16%), flushing (10%), and dizziness (2%). The incidences of hypotension, orthostatic hypotension, and syncope and the rate of discontinuation of treatment due to adverse events were < 2% and were the same in patients taking sildenafil and those taking placebo. Retrospective analysis of the concomitant use of antihypertensive medications (beta blockers, alpha blockers, diuretics, angiotensin-converting enzyme inhibitors, and calcium antagonists) in patients taking sildenafil did not indicate an increase in the reports of adverse events or significant episodes of hypotension compared with patients treated with sildenafil alone. In clinical trials, the incidence of serious cardiovascular adverse events, including stroke and myocardial infarction, was the same for patients treated with sildenafil or placebo. Concurrent disease states, such as renal or hepatic impairment, or concomitant use of inhibitors of the cytochrome P450 isozyme CYP3A4 could increase systemic exposure to sildenafil. Since the US market launch in April 1998, monitoring of spontaneous adverse event reports in association with sildenafil has demonstrated a pattern that is generally consistent with the experience observed during clinical development, with the exception of infrequent reports of priapism. In conclusion, extensive clinical testing has shown that overall treatment with sildenafil for up to 1 year is well tolerated and is associated with a low incidence of adverse events that result in discontinuation of treatment in < 3% of patients. (C) 1999 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Kingston Gen Hosp, Kingston, ON K7L 2V7, Canada. Pfizer Inc, New York, NY USA. Pfizer Cent Res, Sandwich, Kent, England. RP Zusman, RM (reprint author), Massachusetts Gen Hosp, Cardiac Unit, 15 Parkman St,WACC 482, Boston, MA 02114 USA. NR 32 TC 129 Z9 135 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 4 PY 1999 VL 83 IS 5A SI SI BP 35C EP 44C PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 174YF UT WOS:000079063600006 PM 10078541 ER PT J AU De, J Lai, WS Thorn, JM Goldsworthy, SM Liu, XY Blackwell, TK Blackshear, PJ AF De, J Lai, WS Thorn, JM Goldsworthy, SM Liu, XY Blackwell, TK Blackshear, PJ TI Identification of four CCCH zinc finger proteins in Xenopus, including a novel vertebrate protein with four zinc fingers and severely restricted expression SO GENE LA English DT Article DE AU-rich element; deadenylation; mid-blastula transition; mRNA stability ID PRIMARY RESPONSE GENE; C-ELEGANS EMBRYOS; MESSENGER-RNA; TRANSCRIPTION FACTOR; NUCLEOTIDE-SEQUENCE; TRISTETRAPROLIN; DEGRADATION; FAMILY; TIS11; HOMOLOG AB Tristetraprolin (TTP, the prototype of a class of CCCH zinc finger proteins, is a phosphoprotein that is rapidly and transiently induced by growth factors and serum in fibroblasts. Recent evidence suggests that a physiological function of TTP is to inhibit tumor necrosis factor alpha secretion from macrophages by binding to and destabilizing its mRNA (Carballo, E., Lai, W.S., Blackshear, P.J., 1998. Science, 281, 1001-1005). To investigate possible functions of CCCH proteins in early development of Xenopus, we isolated four Xenopus cDNAs encoding members of this class. Based on 49% overall amino acid identity and 84% amino acid identity within the double zinc finger domain, one of the Xenopus proteins (XC3H-1) appears to be the homologue of TTP. By similar analyses, XC3H-2 and XC3H-3 are homologues of ERF-1 (cMG1, TIS11B) and ERF-2 (TIS11D). A fourth protein, XC3H-4, is a previously unidentified member of the CCCH class of vertebrate zinc finger proteins; it contains four Cx(8)Cx(5)Cx(3)H repeats, two of which are YKTEL Cx(8)Cx(5)Cx(3)H repeats that are closely related to sequences found in the other CCCH proteins, Whereas XC3H-1, XC3H-2, and XC3H-3 were widely expressed in adult tissues, XC3H-4 mRNA was not detected in any of the adult tissues studied except for the ovary. Its expression appeared to be limited to the ovary, oocyte, egg and the early embryonic stages leading up to the mid-blastula transition. Its mRNA was highly expressed in oocytes of all ages, and was enriched in the animal pole cytosol of mature oocytes. Maternal expression was also seen with the other three messages, suggesting the possibility that these proteins are involved in regulating mRNA stability in oocyte maturation and/or early embryogenesis. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signel Transduct, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, Off Clin Res, A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM black009@niehs.nih.gov FU NICHD NIH HHS [P0 HD17461] NR 43 TC 40 Z9 44 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 MAR 4 PY 1999 VL 228 IS 1-2 BP 133 EP 145 DI 10.1016/S0378-1119(98)00617-9 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 177JU UT WOS:000079207500014 PM 10072766 ER PT J AU Meng, WY Sawasdikosol, S Burakoff, SJ Eck, MJ AF Meng, WY Sawasdikosol, S Burakoff, SJ Eck, MJ TI Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase SO NATURE LA English DT Article ID PROTOONCOGENE C-CBL; TYROSINE KINASE; EGF RECEPTOR; V-CBL; PROTEIN; RECOGNITION; ASSOCIATION; REGULATOR; PEPTIDE; PRODUCT AB Cbl is an adaptor protein that functions as a negative regulator of many signalling pathways that start from receptors at the cell surface(1-4). The evolutionarily conserved amino-terminal region of Cbl (Cbl-N) binds to phosphorylated tyrosine residues and has cell-transforming activity. Point mutations in Cbl, that disrupt its recognition of phosphotyrosine also interfere with its negative regulatory function and, in the case of v-cbl, with its oncogenic potential(5). In T cells, Cbl-N binds to the tyrosine-phosphorylated inhibitory site of the protein tyrosine kinase ZAP-70(6). Here we describe the crystal structure of Cbl-N, both alone and in complex with a phosphopeptide that represents its binding site in ZAP-70. The structures show that Cbl-N is composed of three interacting domains: a four-helix bundle (4H), an EF-hand(7) calcium-binding domain, and a divergent SH2 domain(8) that was not recognizable from the amino-acid sequence of the protein. The calcium-hound EF hand wedges between the 4H and SH2 domains and roughly determines their relative orientation. In the ligand-occupied structure, the 4H domain packs against the SH2 domain and completes its phosphotyrosine-recognition pocket. Disruption of this binding to ZAP-70 as a result of structure-based mutations in the 4H, EF-hand and SH2 domains confirms that the three domains together form an integrated phosphoprotein-recognition module. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu NR 30 TC 217 Z9 221 U1 1 U2 7 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 4 PY 1999 VL 398 IS 6722 BP 84 EP 90 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 174KG UT WOS:000079033900057 PM 10078535 ER PT J AU Tsao, HS Tahan, SR AF Tsao, HS Tahan, SR TI Keratoacanthoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Tsao, HS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 4 PY 1999 VL 340 IS 9 BP 708 EP 708 DI 10.1056/NEJM199903043400906 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 172ZB UT WOS:000078955200006 PM 10053180 ER PT J AU Gerbitz, A Mautner, J Geltinger, C Hortnagel, K Christoph, B Asenbauer, H Klobeck, G Polack, A Bornkamm, GW AF Gerbitz, A Mautner, J Geltinger, C Hortnagel, K Christoph, B Asenbauer, H Klobeck, G Polack, A Bornkamm, GW TI Deregulation of the proto-oncogene c-myc through t(8;22) translocation in Burkitt's lymphoma SO ONCOGENE LA English DT Article DE c-myc; lambda enhancer; gene regulation; Burkitt's lymphoma; Na-Butyrate ID LOCUS-CONTROL REGION; EPSTEIN-BARR-VIRUS; IMMUNOGLOBULIN-KAPPA-ENHANCERS; HEAVY-CHAIN LOCUS; PROMOTER SHIFT; CHROMOSOMAL TRANSLOCATIONS; HYPERSENSITIVE SITES; GENE-EXPRESSION; SODIUM-BUTYRATE; DOWN-REGULATION AB In Burkitt's lymphoma (BL) cells the proto-oncogene c-myc is juxtaposed to one of the immunoglobulin (Ig) loci on chromosomes 2, 14, or 22, The c-myc gene becomes transcriptionally activated as a consequence of the chromosomal translocation and shows preferential usage of promoter P1 over P2, a phenomenon referred to as promoter shift. In order to define the responsible regulatory elements within the Ig lambda locus, we studied the effect of the human Ig lambda enhancer (HuE lambda) on c-myc expression after stable transfection into BL cells. A 12 kb genomic fragment encompassing HuE lambda, but not HuE lambda alone, strongly activated c-myc expression and induced the promoter shift. To identify additional elements involved in c-myc deregulation, we mapped DNaseI hypersensitive sites within the 12 kb lambda fragment on the construct. Besides one hypersensitive site corresponding to HuE lambda, three additional sites were detected, Two of these elements displayed enhancer activity after transient transfection. The third element did not activate c-myc transcription, but was required for full c-myc activation and promoter shift. Deletion analyses of the c-myc promoter identified the immediate promoter region as sufficient for activation by the Ig lambda locus, but also revealed that induction of the promoter shift requires additional upstream elements. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. GSF Forschungszentrum Umwelt & Gesundheit, Inst Klin Mol Biol & Tumor Genet, D-81377 Munich, Germany. Univ Munich, Genet Inst, D-80336 Munich, Germany. Adolf Butenandt Inst Physiol Chem, D-80336 Munich, Germany. RP Gerbitz, A (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 55 TC 38 Z9 38 U1 6 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 4 PY 1999 VL 18 IS 9 BP 1745 EP 1753 DI 10.1038/sj.onc.1202468 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 174GB UT WOS:000079025000009 PM 10208435 ER PT J AU Nathan, DM AF Nathan, DM TI Treating type 2 diabetes with respect SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID MELLITUS C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Bulfinch 408,55 Fruit St, Boston, MA 02114 USA. NR 13 TC 9 Z9 9 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 2 PY 1999 VL 130 IS 5 BP 440 EP 441 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 172AA UT WOS:000078898100008 PM 10068419 ER PT J AU Gillman, MW Rifas-Shiman, SL Berkey, CS Rockett, HRH Field, AE Camargo, CA Frazier, AL Colditz, GA AF Gillman, MW Rifas-Shiman, SL Berkey, CS Rockett, HRH Field, AE Camargo, CA Frazier, AL Colditz, GA TI Birth weight, breast feeding, and adolescent obesity. SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA 6 BP 1104 EP 1104 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500026 ER PT J AU Lemaitre, RN Siscovick, DS Psaty, BM Anderson, GD Pearce, RM Raghunathan, TE Lin, DY Weinmann, SA Whitsel, EA AF Lemaitre, RN Siscovick, DS Psaty, BM Anderson, GD Pearce, RM Raghunathan, TE Lin, DY Weinmann, SA Whitsel, EA TI Use of inhaled beta-agonists and the risk of primary cardiac arrest SO CIRCULATION LA English DT Meeting Abstract C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Washington, Seattle, WA 98195 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 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P59 BP 1118 EP 1118 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500109 ER PT J AU Whitsel, EA Pearce, RM Ragunathan, TE Lin, DY Rautaharju, PM Weinmann, SA Anderson, GD Arbogast, PG Siscovick, DS AF Whitsel, EA Pearce, RM Ragunathan, TE Lin, DY Rautaharju, PM Weinmann, SA Anderson, GD Arbogast, PG Siscovick, DS TI Electrocardiographic indicators of autonomic dysfunction and risk of primary cardiac arrest among patients without clinically recognized heart disease SO CIRCULATION LA English DT Meeting Abstract C1 Cardiovasc Hlth Res Unit, Seattle, WA USA. Dept Med, Seattle, WA USA. EPICARE Ctr, Winston Salem, NC USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 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 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P58 BP 1118 EP 1118 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500108 ER PT J AU Makino, ER Handy, JW Li, TS Arshavsky, VY AF Makino, ER Handy, JW Li, TS Arshavsky, VY TI The GTPase activating factor for transducin in rod photoreceptors is the complex between RGS9 and type 5 G protein beta subunit SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HETEROTRIMERIC G-PROTEINS; OUTER SEGMENTS; CGMP PHOSPHODIESTERASE; INHIBITORY SUBUNIT; FAMILY; EXPRESSION; MEMBRANES; RHODOPSIN; CASCADE; BRAIN AB Proteins of the regulators of G protein signaling (RGS) family modulate the duration of intracellular signaling by stimulating the GTPase activity of G protein a subunits. It has been established that the ninth member of the RGS family (RGS9) participates in accelerating the GTPase activity of the photoreceptor-specific G protein, transducin. This process is essential for timely inactivation of the phototransduction cascade during the recovery from a photoresponse. Here we report that functionally active RGS9 from vertebrate photoreceptors exists as a tight complex with the long splice variant of the G protein beta subunit (G(beta 5L)) RGS9 and G(beta 5L) also form a complex when coexpressed in cell culture. Our data are consistent with the recent observation that several RGS proteins, including RGS9, contain G protein gamma-subunit like domain that can mediate their association with G(beta 5) (Snow, B. E., Krumins, A. M., Brothers, G. M., Lee, S. F., Wall, M. A., Chung, S., Mangion, J., Arya, S., Gilman, A. G. & Siderovski, D. P. (1998) Proc. Natl. Acad. Sci. USA 95, 13307-13312). We report an example of such a complex whose cellular localization and function are clearly defined. C1 Massachusetts Eye & Ear Infirm, Howe Lab Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Arshavsky, VY (reprint author), Massachusetts Eye & Ear Infirm, Howe Lab Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 10336, R01 EY010336] NR 32 TC 174 Z9 178 U1 0 U2 2 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 MAR 2 PY 1999 VL 96 IS 5 BP 1947 EP 1952 DI 10.1073/pnas.96.5.1947 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600028 PM 10051575 ER PT J AU Ramaswamy, S Nakamura, N Vazquez, F Batt, DB Perera, S Roberts, TM Sellers, WR AF Ramaswamy, S Nakamura, N Vazquez, F Batt, DB Perera, S Roberts, TM Sellers, WR TI Regulation of G(1) progression by the PTEN tumor suppressor protein is linked to inhibition of the phosphatidylinositol 3-kinase/Akt pathway SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROSTATE-CANCER; TYROSINE PHOSPHATASES; GERMLINE MUTATIONS; COWDEN-DISEASE; GENE; CELLS; TRANSFORMATION; PTEN/MMAC1; FREQUENT; PHOSPHORYLATION AB PTEN/MMAC1 is a tumor suppressor gene located on chromosome 10q23. Inherited PTEN/MMAC1 mutations are associated with a cancer predisposition syndrome known as Cowden's disease. Somatic mutation of PTEN has been found in a number of malignancies, including glioblastoma, melanoma, and carcinoma of the prostate and endometrium. The protein product (PTEN) encodes a dual-specificity protein phosphatase and in addition can dephosphorylate certain lipid substrates. Herein, we show that PTEN protein induces a G(1) block when reconstituted in PTEN-null cells. A PTEN mutant associated with Cowden's disease (PTEN;G129E) has protein phosphatase activity yet is defective in dephosphorylating inositol 1,3,4,5-tetrakisphosphate in vitro and fails to arrest cells in G(1). These data suggest a link between induction of a cell-cycle block by PTEN and its ability to dephosphorylate, in vivo, phosphatidylinositol 3,4,5-trisphosphate. In keeping with this notion, PTEN can inhibit the phosphatidylinositol 3,4,5-trisphosphate-dependent Akt kinase, a downstream target of phosphatidylinositol 3-kinase, and constitutively active, but not wild-type, Akt overrides a PTEN G(1) arrest. Finally, tumor cells lacking PTEN contain high levels of activated Akt, suggesting that PTEN is necessary for the appropriate regulation of the phosphatidylinositol 3-kinase/Akt pathway. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sellers, WR (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 50 TC 404 Z9 413 U1 1 U2 5 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 MAR 2 PY 1999 VL 96 IS 5 BP 2110 EP 2115 DI 10.1073/pnas.96.5.2110 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600056 PM 10051603 ER PT J AU Rodrigo, AG Shpaer, EG Delwart, EL Iversen, AKN Gallo, MV Brojatsch, J Hirsch, MS Walker, BD Mullins, JI AF Rodrigo, AG Shpaer, EG Delwart, EL Iversen, AKN Gallo, MV Brojatsch, J Hirsch, MS Walker, BD Mullins, JI TI Coalescent estimates of HIV-1 generation time in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DNA-SEQUENCES; RECOMBINATION; PHYLOGENIES; SELECTION; MODELS; POPULATION; INFECTION; EVOLUTION; ALLELES AB The generation time of HIV Type 1 (HIV-1) in vivo has previously been estimated using a mathematical model of viral dynamics and was found to be on the order of one to two days per generation. Here, we describe a new method based on coalescence theory that allows the estimate of generation times to be derived by using nucleotide sequence data and a reconstructed genealogy of sequences obtained over time. The method is applied to sequences obtained from a long-term nonprogressing individual at five sampling occasions. The estimate of viral generation time using the coalescent method is 1.2 days per generation and is close to that obtained by mathematical modeling (1.8 days per generation), thus strengthening confidence in estimates of a short viral generation time. Apart from the estimation of relevant parameters relating to viral dynamics, coalescent modeling also allows us to simulate the evolutionary behavior of samples of sequences obtained over time. C1 Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Appl Biosyst Inc, Perkin Elmer, Foster City, CA 94404 USA. Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Natl Univ Hosp, Dept Infect Dis, Copenhagen, Denmark. Ontogeny Inc, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Rodrigo, AG (reprint author), Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RI Rodrigo, Allen/E-8905-2015; OI Rodrigo, Allen/0000-0002-8327-7317; brojatsch, jurgen/0000-0002-7424-365X; Delwart, Eric/0000-0002-6296-4484 NR 37 TC 77 Z9 77 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 MAR 2 PY 1999 VL 96 IS 5 BP 2187 EP 2191 DI 10.1073/pnas.96.5.2187 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600069 PM 10051616 ER PT J AU Oxvig, C Lu, CF Springer, TA AF Oxvig, C Lu, CF Springer, TA TI Conformational changes in tertiary structure near the ligand binding site of an integrin I domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID A-DOMAIN; CRYSTAL-STRUCTURE; VONWILLEBRAND-FACTOR; COMPLEMENT RECEPTOR; SIGNAL-TRANSDUCTION; MAC-1 CD11B/CD18; DIVALENT-CATION; ALPHA-SUBUNIT; CELL-ADHESION; ACTIVATION AB For efficient ligand binding, integrins must be activated. Specifically, a conformational change has been proposed in a ligand binding domain present within some integrins, the inserted (I) domain [Lee, J., Bankston, L., Arnaout, M. & Liddington, R. C. (1995) Structure (London) 3, 1333-1340]. This proposal remains controversial, however, despite extensive crystal structure studies on the I domain [Lee, J., Bankston, L., Arnaout, M. & Liddington, R C. (1995) Structure (London) 3, 1333-1340; Liddington, R. & Bankston, L. (1998) Structure (London) 6, 937-938; Qu, A. & Leahy, D. J. (1996) Structure (London) 4, 931-942; and Baldwin, E. T., Sarver, R. W., Bryant; G. L., Jr., Curry, K. A., Fairbanks, M. B., Finzel, B. C., Garlick, R. L., Heinrikson, RL., Horton, N. C. & Belly, L. L. (1998) Structure (London) 6, 923-935]. By defining the residues present in the epitope of a mAb against the human Mac-1 integrin (alpha70 years, angina, diabetes, Q wave on EKG, history of congestive heart failure) to predict adverse cardiac events following major vascular surgery has previously been demonstrated. However, the utility of these criteria for lower-extremity amputation is not well established. To determine the value of the Eagle criteria for predicting cardiac morbidity and operative mortality following major lower-extremity amputation, we reviewed 214 consecutive procedures performed at two institutions over a 3-year period. Mean age was 62.7 years and 85% of the patients were male. Diabetes was the most frequent Eagle criterion (74%), The mean number of Eagle criteria was 1.6. Fifty-six percent of the amputations were below the knee, 24% were above the knee, and 20% were guillotine. On multivariate regression analysis, the presence of two or more Eagle criteria (16% vs. 4%, p = 0.04) and decompensated heart failure (39% vs. 7%, p = 0.003) were predictive of adverse cardiac events. The only predictor of postoperative mortality was the presence of two or more Eagle criteria (15% vs. 4%, p = 0.004). Our evaluation of the results of this study led us to conclude that patients requiring major lower-extremity amputation for major vascular disease who have multiple Eagle criteria or decompensated congestive heart failure are at high risk for adverse cardiac events and postoperative death. These findings should be used to guide perioperative cardiac evaluation and therapy. C1 Univ Calif Los Angeles, Harbor Med Ctr, Dept Surg, Div Vasc Surg, Torrance, CA 90509 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA. W Los Angeles Vet Affairs Med Ctr, Div Vasc Surg, Dept Surg, W Los Angeles, CA USA. RP de Virgilio, C (reprint author), Univ Calif Los Angeles, Harbor Med Ctr, Dept Surg, Div Vasc Surg, Box 25,1000 W Carson St, Torrance, CA 90509 USA. NR 9 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAR PY 1999 VL 13 IS 2 BP 204 EP 208 DI 10.1007/s100169900243 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 170BT UT WOS:000078786100014 PM 10072463 ER PT J AU Wang, MB Alavi, S Engstrom, M Lee, J Namazie, A Moatamed, F Srivatsan, ES AF Wang, MB Alavi, S Engstrom, M Lee, J Namazie, A Moatamed, F Srivatsan, ES TI Detection of chromosome 11q13 amplification in head and neck cancer using fluorescence in situ hybridization SO ANTICANCER RESEARCH LA English DT Article DE 11q13 amplification; head and neck cancer; FISH ID SQUAMOUS-CELL CARCINOMAS; DOUBLE MINUTE CHROMOSOMES; CYCLIN D1; GENE AMPLIFICATION; POOR-PROGNOSIS; BLADDER-CANCER; ABERRATIONS; TUMORS; LINES; REGION AB Background: Head and neck squamous cell carcinoma (HNSCC) remains a cancer with one of the lowest five-year survival rates. Despite a better understanding of the disease and recent advances in diagnosis and treatment, survival rates for HNSCC patients have not improved. Chromosomal abnormalities are common in HNSCC, and aberrations of chromosome 11q13 have been correlated with a poor prognosis. Materials and Methods: In this study we utilized fluorescence in situ hybridization (FISH) to determine the incidence of 11q13 amplification in twenty primary HNSCC tumors. INT-2 was used as the 11q13 probe, and 9 and 11 centromeric probes were used as controls. Results: Polysomy, greater than two copies of chromosome 11, was found in 2 of 20 tumors. INT2 (11q13) amplification was found in 3 other tumors. Conclusions: These preliminary studies indicate that analysis of a larger sample of tumors using FISH may yield important diagnostic and prognostic information about head and neck tumors. C1 Univ Calif Los Angeles, Sch Med, Div Head & Neck Surg, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Uppsala Hosp, Dept Otorhinolaryngol & Head & Neck Surg, Uppsala, Sweden. RP Wang, MB (reprint author), Univ Calif Los Angeles, Sch Med, Div Head & Neck Surg, CHS 62-132,10833 LeConte Ave, Los Angeles, CA 90095 USA. NR 36 TC 21 Z9 21 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 1999 VL 19 IS 2A BP 925 EP 931 PG 7 WC Oncology SC Oncology GA 202JQ UT WOS:000080649100005 PM 10368635 ER PT J AU Ripple, MO Hagopian, K Oberley, TD Schatten, H Weindruch, R AF Ripple, Maureen O. Hagopian, Kevork Oberley, Terry D. Schatten, Heide Weindruch, Richard TI Androgen-Induced Oxidative Stress in Human LNCaP Prostate Cancer Cells Is Associated with Multiple Mitochondrial Modifications SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article AB We investigated the role of androgen-induced oxidative stress in prostate cancer using responsive LNCaP human prostate cancer cell line exposed to a 1-nM concentration of the synthetic androgen R1881 ( which correlates with serum androgen levels). Such exposure, which decreases growth rate and increases oxidative stress in LNCaP cells, induced statistically significant mitochondrial changes. A 40% increase in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction, indicative of mitochondrial dehydrogenase activity, occurred 24 hr after androgen treatment. This change preceded 50-110% increases, 40-96 hr after R1881 exposure, in levels of cellular peroxides and hydroxyl radicals as measured by 2'7'-dicholorofluorescin diacetate (DCF) fluorescence. On the basis of electron microscopy measurements, R1881 treatment increased the area fraction of mitochondria per cell by similar to 100% at 72 hr. In agreement, mitochondrial mass at 96 hr, evaluated by the fluorescent dye nonyl acridine orange (NAO), was 80% higher in treated cells. R1881 exposure for 24 hr lowered the activities of electron transport system (ETS) complexes, I, II, and IV by 17-27% and ATP levels by 50%. The ETS inhibitors, rotenone and antimycin A, lowered androgen-induced DCF fluorescence readings to control levels thereby suggesting ETS involvement in androgen-induced oxidant production. Addition of alpha-tocopherol succinate abrogated R1881-induced elevations in MTT reduction. In sum, androgens may, directly or indirectly, contribute to oxidative stress in LNCaP cells by regulating mitochondrial number, activity, and oxidant production by mechanisms that are, at least in part, sensitive to an antioxidant. Antiox. Redox Signal. 1, 71-81. C1 [Ripple, Maureen O.; Hagopian, Kevork; Weindruch, Richard] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. [Ripple, Maureen O.; Weindruch, Richard] Univ Wisconsin, Inst Aging, Univ Wisconsin Comprehens Canc Ctr, Madison, WI 53706 USA. [Ripple, Maureen O.; Weindruch, Richard] Univ Wisconsin, Dept Med, Univ Wisconsin Comprehens Canc Ctr, Madison, WI 53706 USA. [Hagopian, Kevork; Weindruch, Richard] Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53706 USA. [Oberley, Terry D.] Univ Wisconsin, Dept Pathol, Madison, WI 53706 USA. [Schatten, Heide] Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. RP Weindruch, R (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, GRECC 4D, Madison, WI 53705 USA. EM rhweindr@facstaff.wisc.edu FU National Institute on Aging [T32 A G 00213]; Madison VA GRECC [99-04] FX This work was supported by National Institute on Aging grant T32 A G 00213 (R.W.). This is publication #99-04 from the Madison VA GRECC. NR 45 TC 30 Z9 32 U1 0 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD SPR PY 1999 VL 1 IS 1 BP 71 EP 81 DI 10.1089/ars.1999.1.1-71 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA V10YV UT WOS:000207500200006 PM 11225734 ER PT J AU Yablon, AD Nishioka, NS Mikic, BB Venugopalan, V AF Yablon, AD Nishioka, NS Mikic, BB Venugopalan, V TI Measurement of tissue absorption coefficients by use of interferometric photothermal spectroscopy SO APPLIED OPTICS LA English DT Article ID DYNAMIC OPTICAL-PROPERTIES; EXCIMER LASER ABLATION; SOLID-STATE LASER; BIOLOGICAL TISSUE; ORGANIC POLYMERS; COLLAGEN; CORNEA; WATER; RADIOMETRY AB We describe a spectroscopic technique called interferometric photothermal spectroscopy (IPTS) that can measure the absorption coefficient of pulsed laser radiation in nonscattering tissue samples. The technique is suitable for measuring effective absorption coefficients from 10(3) to 10(5) cm(-1). IPTS is particularly attractive because it requires minimal disturbance of the sample. These features indicate potential use for in vivo measurements of tissue absorption coefficients. To validate the technique, the absorption coefficient of pulsed Q-switched Er:YSGG (2.79-mu m) radiation in pure water was measured to be 5200 (+/- 500) cm(-1) when IPTS was used, in agreement with other published values. IPTS was also used to measure the absorption coefficient of pulsed ArF excimer laser radiation (193 nm) in bovine corneal stroma (in vitro), giving a value of 1.9 (+/- 0.4) x 10(4) cm(-1). (C) 1999 Optical Society of America. OCIS codes: 120.3180, 120.4290, 120.6810, 170.3660, 170.6930, 300.6430. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Univ Calif Irvine, Beckman Laser Inst, Laser Microbeam & Med Program, Irvine, CA 92612 USA. RP Venugopalan, V (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. EM vasan@bli.uci.edu NR 33 TC 16 Z9 16 U1 0 U2 0 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD MAR 1 PY 1999 VL 38 IS 7 BP 1259 EP 1272 DI 10.1364/AO.38.001259 PG 14 WC Optics SC Optics GA 173ER UT WOS:000078968700027 PM 18305741 ER PT J AU Van Remmen, H Salvador, C Yang, H Huang, TT Epstein, CJ Richardson, A AF Van Remmen, H Salvador, C Yang, H Huang, TT Epstein, CJ Richardson, A TI Characterization of the antioxidant status of the heterozygous manganese superoxide dismutase knockout mouse SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE MnSOD; glutathione; antioxidant enzymes; knockout mice ID GLUTATHIONE-PEROXIDASE; TRANSGENIC MICE; OXYGEN-TOXICITY; EXPRESSION; DEFICIENT; CATALASE; ENZYMES; SENSITIVITY; HYPEROXIA; CELLS AB The antioxidant status of several tissues (liver, kidney, lung, brain, heart, muscle, stomach, and spleen) fi om heterozygous manganese superoxide dismutase (MnSOD) mutant mice (Sod2(-/+)) was characterized. The activity of MnSOD was decreased (30 to 80%) in all tissues examined. The levels of mRNA coding for the major antioxidant enzymes (CuZnSOD, catalase, and glutathione peroxidase) were not significantly altered in liver, kidney, heart, lung, or brain in the Sod2(-/+) mice. The activities of the enzymes were not altered in any of these tissues, with the exception of a decrease in glutathione peroxidase activity in muscle in the Sod2(-/+) mice compared to the Sod2(+/+) mice. Thus, there was no up-regulation of the activities of the major antioxidant enzymes to compensate for the decrease in MnSOD activity. Reduced glutathione levels were 30 to 50% lower in the lung, brain, and muscle of the Sod2(-/+) mice compared to the wild-type Sod2(+/+) mice. In addition, the ratio of GSH/GSSG was decreased approximately 50% in Sod2(-/+) muscle, indicating that the decrease in MnSOD activity in the Sod2(-/+) mice results in some degree of oxidative stress in this tissue. (C) 1999 Academic Press. C1 Univ Texas, Hlth Sci Ctr, Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst,Audie L Murphy Div, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Van Remmen, H (reprint author), Audie Murphy VA Hosp, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM vanremmen@uthscsa.edu FU NIA NIH HHS [AG15908, P03 AG13319, AG08938] NR 26 TC 116 Z9 118 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 1 PY 1999 VL 363 IS 1 BP 91 EP 97 DI 10.1006/abbi.1998.1060 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 174EG UT WOS:000079020700011 PM 10049502 ER PT J AU Duke, D Byers, HR Sober, AJ Anderson, RR Grevelink, JM AF Duke, D Byers, HR Sober, AJ Anderson, RR Grevelink, JM TI Treatment of benign and atypical nevi with the normal-mode ruby laser and the Q-switched ruby laser - Clinical involvement but failure to completely eliminate nevomelanocytes SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY APR 06, 1998 CL SAN DIEGO, CALIFORNIA SP Amer Soc Laser Med & Surg ID CONGENITAL MELANOCYTIC NEVI; CUTANEOUS MELANOMA; SELECTIVE PHOTOTHERMOLYSIS; MALIGNANT-MELANOMA; DYSPLASTIC NEVI; RISK; LESIONS; TATTOOS; PULSES; NM AB Objective: To evaluate the effect of normal-mode and Q-snitched ruby laser light (694 nm) on nevomelanocytes of benign, atypical, and congenital nevi. Design: Half of the lesion of each of 31 nevi was treated with either the Q-switched ruby laser or the normal-mode ruby laser or both; the other half of the lesion was covered with aluminum foil and was not treated. Setting: A university-affiliated, hospital-based laser center. Patients: Sixteen patients with a total of 31 melanocytic nevi were enrolled in the study. Interventions: All nevi were evaluated by at least 2 dermatologists to assess the degree of clinical atypia. Photographs were taken before and immediately after treatment and at each follow-up visit. The digital imaging system was used to evaluate the number of melanocytes in a measured length of basement membrane zone. Main Outcome Measure: Three individual readings (number of melanocytes per unit length) were taken on both the control and treated halves and then compared to quantitate treatment effect. All analyses used averages from 3 measurements. A Student paired t test was used to compare the treated and untreated sides. Results: Sixteen (52%) of the nevi showed a clinically visible decrease in pigment on the treatment side at the 4-week follow-up visit. Conclusion: No lesions had complete histologic removal of all nevomelanocytes. Therefore, 1 or 2 laser treatments are not sufficient to cause complete removal of a lesion either clinically or histologically. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Yale Med Sch, Dept Dermatol, New Haven, CT USA. Boston Univ, Sch Med, Dept Dermatol, Dermatopathol Sect, Boston, MA 02118 USA. Eastern Connecticut Dermatol, Groton, CT USA. RP Grevelink, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser Ctr, POB 501,275 Cambridge St, Boston, MA 02114 USA. NR 32 TC 48 Z9 51 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 1999 VL 135 IS 3 BP 290 EP 296 DI 10.1001/archderm.135.3.290 PG 7 WC Dermatology SC Dermatology GA 177DN UT WOS:000079192300009 PM 10086450 ER PT J AU Growdon, JH AF Growdon, JH TI Biomarkers of Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Review ID EPSILON-4; PROTEIN AB A definitive diagnosis of Alzheimer disease (AD) depends on finding widespread neurofibrillary tangles and plentiful neuritic plaques in the brain of an individual with a clinical diagnosis of progressive dementia.(1) Using contemporary diagnostic criteria, the antemortem diagnosis of probable AD in centers specialized for AD is confirmed 80% to 90% of the time. There is the suspicion, but no firm data, that diagnostic accuracy is much lower outside of practices dedicated to patients with dementia. Furthermore, the diagnostic workup is expensive. In most settings, the evaluation generally includes a careful medical history and physical examination; neurologic examination (and psychiatric consultation as indicated); laboratory blood studies to exclude underlying metabolic and medical illnesses that masquerade as AD; a mental status assessment and formal cognitive tests; and a computed tomographic scan or magnetic resonance imaging of the brain.(2) Because these procedures are time-consuming and costly, there is a need to identify biological tests that can circumvent aspects of this workup and point the physician to the correct diagnosis. It would be highly desirable to measure a substance or substances in blood or urine samples or cerebrospinal fluid (CSF) that would lead to a positive diagnosis of AD without the need for specialized dementia clinics and the expense and time of standard diagnostic evaluations. In response to this need, the Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging convened a working group in 1997 to examine the status of various antemortem markers for AD. The consensus statement of this group, entitled "Molecular and Biochemical Markers of AD," was published in 1998.(3) The consensus statement first defined the characteristics of an ideal biomarker, and then outlined the steps required for a proposed biomarker to achieve acceptance by the medical community. Finally, the statement reviewed the current state of all proposed biological markers. The workshop participants observed that none of the current biomarkers had yet achieved universal acceptance and concluded none fully met the consensus criteria for an ideal marker. Nonetheless, several tests were identified as good markers for familial AD, and several other tests showed promise as a diagnostic aid for sporadic AD. The purpose of this review is to put these recommendations into a practical context. What does the consensus statement tell the practicing clinician? How do the opinions in the consensus statement affect clinical practice in diagnosing and treating patients with dementia?. C1 Massachusetts Gen Hosp, Dept Neurol, Wang Ambulatory Ctr, Boston, MA 02114 USA. RP Growdon, JH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang Ambulatory Ctr, Suite 830,John H 15 Parkman St, Boston, MA 02114 USA. NR 14 TC 65 Z9 66 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 1999 VL 56 IS 3 BP 281 EP 283 DI 10.1001/archneur.56.3.281 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 173TD UT WOS:000078995100003 PM 10190817 ER PT J AU Lessell, S AF Lessell, S TI Nonarteritic anterior ischemic optic neuropathy - Enigma variations SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID FLUORESCEIN ANGIOGRAPHY; NERVE HEAD; DISEASE; RISK C1 Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, Boston, MA 02114 USA. RP Lessell, S (reprint author), Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, 243 Charles St, Boston, MA 02114 USA. NR 27 TC 44 Z9 44 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 1999 VL 117 IS 3 BP 386 EP 388 PG 3 WC Ophthalmology SC Ophthalmology GA 175VD UT WOS:000079115500012 PM 10088818 ER PT J AU Langston, DP AF Langston, DP TI Oral acyclovir suppresses recurrent epithelial and stromal herpes simplex SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID KERATITIS; EPIDEMIOLOGY; ROCHESTER; MINN C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Langston, DP (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 8 TC 5 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 1999 VL 117 IS 3 BP 391 EP 392 PG 2 WC Ophthalmology SC Ophthalmology GA 175VD UT WOS:000079115500014 PM 10088820 ER PT J AU Tulvatana, W Adamian, M Berson, EL Dryja, TP AF Tulvatana, W Adamian, M Berson, EL Dryja, TP TI Photoreceptor rosettes in autosomal dominant retinitis pigmentosa with reduced penetrance SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 12-14, 1998 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol AB We performed histopathologic and immunofluorescence studies of autopsy eyes from a 73-year-old woman with autosomal dominant retinitis pigmentosa from a family with reduced penetrance. Light microscopic examination showed extensive photoreceptor loss in most regions. In the temporal midperiphery of the retina, there were patches of remaining photoreceptors, some arranged in rosettes. Electron microscopic examination showed that these rosettes were composed mostly of rods, with a few conelike inner segments. The malformed photoreceptor elements in the rosette lumens stained positively with anti-rhodopsin, but not with anti-red- and green-cone opsin or anti-blue-cone opsin. To our knowledge, this is the first report of photoreceptor rosettes containing rod photoreceptors in a case of retinitis pigmentosa. Future studies of additional patients will be needed to determine if the rod-abundant rosettes seen in our patient are a characteristic finding of autosomal dominant retinitis pigmentosa with reduced penetrance. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, David G Cogan Eye Pathol Lab, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM dryja@helix.mgh.harvard.edu NR 8 TC 25 Z9 25 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 1999 VL 117 IS 3 BP 399 EP 402 PG 4 WC Ophthalmology SC Ophthalmology GA 175VD UT WOS:000079115500018 PM 10088824 ER PT J AU Espaillat, A Aiello, LP Arrigg, PG Villalobos, R Silver, PM Cavicchi, RW AF Espaillat, A Aiello, LP Arrigg, PG Villalobos, R Silver, PM Cavicchi, RW TI Canthaxanthine retinopathy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. NR 7 TC 8 Z9 8 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 1999 VL 117 IS 3 BP 412 EP 413 PG 2 WC Ophthalmology SC Ophthalmology GA 175VD UT WOS:000079115500023 PM 10088829 ER PT J AU Tanaka, M Margolis, HC AF Tanaka, M Margolis, HC TI Release of mineral ions in dental plaque following acid production SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE enamel; demineralization; caries; plaque; plaque fluid ID TOOTH DEMINERALIZATION; CARIES-FREE; FLUORIDE; FLUID; CALCIUM; SALIVA; PH; INDIVIDUALS; RINSE; NAF AB The release of appreciable amounts of calcium, phosphate and fluoride found in whole plaque into the plaque-fluid phase, following bacterial acid production, can potentially reduce the driving force for tooth demineralization. However, limited information is available on this topic, particularly on the release of fluoride. This study sought to determine the change in calcium, phosphate and fluoride concentrations In plaque fluid after sucrose exposure. 48 h overnight-fasted supragingival plaque samples were collected from all tooth surfaces (with the exception of the lower lingual anterior teeth) of one half of an individual mouth, following a 1 min water rinse. Plaque samples were then collected from the other half of the same mouth, following a 292 mM sucrose rinse. Plaque fluid was isolated by centrifugation and analysed for total calcium and phosphate (ion chromatography) and for free fluoride (ion-specific electrode). Samples were collected from seven individuals. Following sucrose exposure, plaque-fluid pH decreased significantly from 6.5 +/- 0.3 to 5.4 +/- 0.2; calcium concentrations (mmol/l) also increased significantly (p < 0.01) from 1.9 +/- 0.5 to 5.0 +/- 2.1. Fluoride and phosphate concentrations in plaque fluid, however, did not increase significantly after sucrose exposure: mean concentrations (mmol/l) of fluoride after the water and sucrose rinses were 0.006 +/- 0.003 and 0.005 +/- 0.002, respectively, and mean phosphate concentrations (mmol/l) were 11.0 +/- 2.0 and 12.0 +/- 3.0, respectively. When results were expressed per wet plaque weight, phosphate concentrations were also found to increase significantly. The same trends were observed when additional plaque samples were treated in vitro with sucrose: fluoride-ion activity did not increase in plaque under in vivo-like conditions. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. Tokyo Med & Dent Univ, Dept Pediat Dent, Bunkyo Ku, Tokyo 1138549, Japan. RP Margolis, HC (reprint author), Forsyth Dent Ctr, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-07493] NR 23 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD MAR PY 1999 VL 44 IS 3 BP 253 EP 258 DI 10.1016/S0003-9969(98)00125-3 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 180JX UT WOS:000079383400006 PM 10217516 ER PT J AU Cunningham, MT Praestgaard, J Styer, PE Brandt, JT Fairweather, RB Laposata, M Olson, JD Sosolik, RC Triplett, DA AF Cunningham, MT Praestgaard, J Styer, PE Brandt, JT Fairweather, RB Laposata, M Olson, JD Sosolik, RC Triplett, DA TI A method for proficiency testing of small peer groups in the College of American Pathologists Coagulation Surveys SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article AB Objective. - To develop a grading scheme for the proficiency testing of small peer groups of fewer than 10 members for the prothrombin time (PT) and activated partial thromboplastin time (APTT). Methods. - A modified target value for small peer groups was derived based an the assumption that measurement variability in the PT and APTT is more greatly influenced by variations in reagents than in instruments. Criteria for grading were established by statistical simulation to achieve misclassification errors of less than 5% for both incorrectly passing and failing participants. College of American Pathologists Coagulation Survey data were analyzed to determine the number of additional laboratories graded using the proposed scheme, as well as the failure rates among participants in the small peer groups. Results. - The modified target value for small peer groups is a weighted average between the mean of the peer group and the mean of all participants using the same reagent (reagent group). Peer groups with as few as 4 members can be graded provided that specific criteria are satisfied: there must be at least 5 peer groups for the same reagent, at least 3 of these 5 peer groups must have more than 3 members, and the coefficient of variation for the reagent group must be less than 10%. This proposed grading scheme decreased the number of ungraded laboratories by 44% to 46% for the PT and 42% to 55% for the APTT. The percentage of failing grades among participants in the small peer groups ranged from 1.3% to 4.1% far the PT and 1.4% to 7.2% for the APTT. These failure rates were 2.8- to 13.0-fold higher than the failure rates in large peer groups (P less than or equal to .05). Conclosions. - The proposed small peer group grading scheme can improve the effectiveness of College of American Pathologists proficiency testing for the PT and APTT and may also be generally applicable to other test methods and analytes. C1 Vet Affairs Med Ctr, Dept Pathol & Lab Med, Kansas City, MO 64128 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Coll Amer Pathologists, Northfield, IL USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. Massachusetts Gen Hosp, Div Clin Labs, Boston, MA 02114 USA. Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. So Ohio Med Ctr, Dept Pathol, Portsmouth, OH USA. Ball Mem Hosp, Dept Pathol, Muncie, IN 47303 USA. RP Cunningham, MT (reprint author), Vet Affairs Med Ctr, Dept Pathol & Lab Med, DRC-113,4801 Linwood Blvd, Kansas City, MO 64128 USA. NR 3 TC 7 Z9 8 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 1999 VL 123 IS 3 BP 199 EP 205 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 174MJ UT WOS:000079038700004 PM 10086507 ER PT J AU Jellinek, MS Murphy, JM Little, M Pagano, ME Comer, DM Kelleher, KJ AF Jellinek, MS Murphy, JM Little, M Pagano, ME Comer, DM Kelleher, KJ TI Use of the pediatric symptom checklist to screen for psychosocial problems in pediatric primary care - A national feasibility study SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PSYCHIATRIC-DISORDERS; RESEARCH NETWORKS; RISK-FACTORS; CHILDREN; PSYCHOPATHOLOGY; DYSFUNCTION; PREVALENCE; OUTPATIENTS AB Background: Routine use of a brief psychosocial screening instrument has been proposed as a means of improving recognition, management, and referral of children's psychosocial morbidity in primary care. Objective: To assess the feasibility of routine psychosocial screening using the Pediatric Symptom Checklist (PSC) in pediatrics by using a brief version of the checklist in a large sample representative of the full range of pediatric practice settings in the United States and Canada. We evaluated large-scale screening and the performance of the PSC in detecting psychosocial problems by (1) determining whether the prevalence of psychosocial dysfunction identified by the PSC was consistent with findings in previous, smaller samples; (2) assessing whether the prevalence of positive PSC screening stores varied by population subgroups; and (3) determining whether the PSC was completed by a significant proportion of parents from all subgroups and settings. Patients and Methods: Twenty-one thousand sixty-five children between the ages of 4 and 15 years were seen in 2 large primary care networks: the Ambulatory Sentinel Practice Network and the Pediatric Research in Office Settings network, involving 395 pediatric and family practice clinicians in et states, Puerto Rico, and 4 Canadian provinces. Parents were asked to complete a brief questionnaire that included demographic information, history of mental health services, the 35-item PSC, and the number of pediatric visits within the past 6 months. Results: The overall prevalence rates of psychosocial dysfunction as measured by the PSC in school-aged and preschool-aged pediatric outpatients (13% and 10%, respectively) were nearly identical to the rates that had been reported in several smaller samples (12%-14% among school-aged children and 7%-14% among preschoolers). Consistent with previous findings, children from low-income families were twice as likely to be scored as dysfunctional on the PSC than were children from higher-income families. Similarly, children from single-parent as opposed to those from 2-parent families and children with a past history of mental health services showed an elevated risk of psychosocial impairment. The current study was the first to demonstrate a 50% increase in risk of impairment for male children. The overall rate of completed forms was 97%, well within an acceptable range, and at least 94% of the parents in each sociodemograghic subgroup completed the PSC form. Conclusions: Use of the PSC offers an approach to the recognition of psychosocial dysfunction that is sufficiently consistent across groups and locales to become part of comprehensive pediatric care in virtually all outpatient settings. In addition to its clinical utility, the consistency and widespread acceptability of the PSC make it well suited for the next generation of pediatric mental health services research, which can address whether earlier recognition of and intervention for psychosocial problems in pediatrics will lead to cost-effective outcomes. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Boston, MA 02114 USA. Univ Pittsburgh, Child Serv, Pittsburgh, PA 15260 USA. RP Jellinek, MS (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, ACC 725, Boston, MA 02114 USA. EM mjellinek@partners.org RI Kelleher, Kelly/E-3361-2011 FU NIAAA NIH HHS [L30 AA014994]; NIMH NIH HHS [MH50629]; PHS HHS [MCJ-177022] NR 39 TC 174 Z9 178 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 1999 VL 153 IS 3 BP 254 EP 260 PG 7 WC Pediatrics SC Pediatrics GA 174DV UT WOS:000079019600007 PM 10086402 ER PT J AU Wernick-Robinson, M Krebs, DE Giorgetti, MM AF Wernick-Robinson, M Krebs, DE Giorgetti, MM TI Functional reach: Does it really measure dynamic balance? SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID STIMULUS PARAMETERS; REHABILITATION; RESPONSES; STRATEGIES; DISORDERS; AGE AB Background: Functional reach (FR) is a new clinical measurement intended to assess dynamic balance. The purposes of this study were (1) to measure the mean FR distance in healthy elders compared with individuals with known balance impairments, (2) to analyze the extent to which FR measures dynamic balance, and (3) to describe movement strategies used during FR. Methods: Thirteen healthy elders and 15 individuals with vestibular hypofunction (VH) were tested during FR and free gait. Whole body kinematic and kinetic data including the center of gravity (CG) and center of pressure (CP) using 11 body segments and two force plates, respectively, were collected. Results: There was no difference in FR distance between healthy elders and individuals with VH. FR distance was not correlated to lateral stability measures, but was related to anterior-posterior postural control measures of FR (r = .69 to .84) in both groups. Although FR distance strongly correlated with maximum moment arm during FR in both groups, the correlations were not as strong when the subjects were then classified by movement strategy. The mean moment arm during FR was significantly less than that of free gait. Conclusions: These data suggest FR does not measure dynamic balance; healthy elders and balance-impaired individuals with vestibular dysfunction attained the same FR distance and did so without increasing the moment arm during or at the end of FR. Recording the strategy used during FR, however, may provide other valuable information necessary in addressing balance control. Clinical implications of assessing movement strategy are discussed. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Phys Therapy Dept, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess Grad Program Phys Therapy, Boston, MA 02114 USA. RP Wernick-Robinson, M (reprint author), Massachusetts Gen Hosp, PT Serv, WACC 128,15 Parkman St, Boston, MA 02114 USA. FU NIA NIH HHS [R01 AG 11255, P50AG11669, R01 AG 12561] NR 36 TC 52 Z9 61 U1 4 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 1999 VL 80 IS 3 BP 262 EP 269 DI 10.1016/S0003-9993(99)90136-3 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 173RX UT WOS:000078994500005 PM 10084433 ER PT J AU Josephson, L Tung, CH Moore, A Weissleder, R AF Josephson, L Tung, CH Moore, A Weissleder, R TI High-efficiency intracellular magnetic labeling with novel superparamagnetic-tat peptide conjugates SO BIOCONJUGATE CHEMISTRY LA English DT Article ID T-CELLS; PROTEIN; DELIVERY AB A biocompatible, dextran coated superparamagnetic iron oxide particle was derivatized with a peptide sequence from the HIV-tat protein to improve intracellular magnetic labeling of different target cells. The conjugate had a mean particle size of 41 nm and contained an average of 6.7 tat peptides. Derivatized particles were internalized into lymphocytes over 100-fold more efficiently than nonmodified particles, resulting in up to 12.7 x 10(6) particles/cell. Internalized particles localized in cytoplasm and nuclear compartments as demonstrated by fluorescence microscopy and immunohistochemistry. Labeled cells were highly magnetic, were detectable by NMR imaging, and could be retained on magnetic-separation columns. The described method has potential applications for in vivo tracking of magnetically labeled cells by MR imaging and for recovering intracellularly labeled cells from organs. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. RI Meares, Claude/A-8345-2011; OI Tung, Ching-Hsuan/0000-0001-6648-6195 NR 27 TC 692 Z9 735 U1 5 U2 96 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 1999 VL 10 IS 2 BP 186 EP 191 DI 10.1021/bc980125h PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 177YH UT WOS:000079238300005 PM 10077466 ER PT J AU DeCaprio, JA AF DeCaprio, JA TI The role of the J domain of SV40 large T in cellular transformation SO BIOLOGICALS LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; LARGE TUMOR-ANTIGEN; PRB-RELATED PROTEINS; SIMIAN VIRUS-40; GOVERNING SEQUENCE; DNA-SEQUENCES; BINDING; PRODUCT; CYCLE; P107 AB SV40 large T antigen (TAg)-mediated transformation is dependent on binding to p53 and the retinoblastoma tumor suppressor protein (pRB) and inactivating their growth suppressive functions. Transformation minimally requires three regions of TAg: a C-terminal domain that mediates binding to p53; the LXCXE motif (residues 103-107), necessary for binding to pRB and the related proteins p107 and p130; and an N-terminal domain (residues 1-82) that contains homology to the J domain found in cellular DnaJ/Hsp40 molecular chaperone proteins. We have found that the N-terminal J domain of T Ag cooperates with the LXCXE motif to inactivate the growth suppressive functions of the pRB-related proteins. (C) 1999 The International Association for Biologicals. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 36 TC 46 Z9 48 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 1999 VL 27 IS 1 BP 23 EP 28 DI 10.1006/biol.1998.0173 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 223LM UT WOS:000081842600003 PM 10441399 ER PT J AU Jensen, LJ Schmitt, BM Berger, UV Nsumu, NN Boron, WF Hediger, MA Brown, D Breton, S AF Jensen, LJ Schmitt, BM Berger, UV Nsumu, NN Boron, WF Hediger, MA Brown, D Breton, S TI Localization of sodium bicarbonate cotransporter (NBC) protein and messenger ribonucleic acid in rat epididymis SO BIOLOGY OF REPRODUCTION LA English DT Article ID CARBONIC-ANHYDRASE; MITOCHONDRIA-RICH; CULTURED-CELLS; EXPRESSION; ACIDIFICATION; SPERMATOZOA; PH; GLYCOSYLATION; CONDUCTANCES; MAMMALS AB An acidic environment is important for sperm maturation in the epididymis and also helps to maintain mature sperm in an immotile state during storage in this organ. Both an Na+/H+ exchanger and an H(+)ATPase have been implicated in this process. The H(+)ATPase is concentrated in specialized apical (and/or narrow) and clear cells of the epididymis, while the Na+/H+ exchanger has not yet been localized in situ, As in other proton-secreting epithelia, bicarbonate transport occurs in the epididymis, where it is implicated in luminal acidification. In this study we used an antibody raised against a fusion protein (maltose-binding protein: MBP-NBC-5) from the C-terminus of the recently cloned rat kidney Na+/HCO3- cotransporter (NBC) to localize this protein in the epididymis and vas deferens of the Pat. The distribution of the respective mRNA was mapped by in situ hybridization. NBC message was strongly expressed in the initial segment and the intermediate zone of the epididymis, and the NBC-5 antibody gave a strong basolateral staining in both principal cells and apical/narrow cells in this region. Western blotting revealed a single band at about 160 kDa in the epididymis. The intensity of staining as well as mRNA levels decreased in the cauda epididymidis and in the vas deferens, where only weak staining was seen. Basolateral NBC may function in parallel with apical proton secretion to regulate luminal acidification and/or bicarbonate reabsorption in the excurrent duct system. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06520 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. RI Jensen, Lars/A-9340-2008; OI Boron, Walter/0000-0003-4741-7287 FU NIDDK NIH HHS [DK 38452] NR 35 TC 51 Z9 54 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 1999 VL 60 IS 3 BP 573 EP 579 DI 10.1095/biolreprod60.3.573 PG 7 WC Reproductive Biology SC Reproductive Biology GA 170RY UT WOS:000078820900006 PM 10026101 ER PT J AU Pfleiderer, B Moore, A Tokareva, E Ackerman, JL Garrido, L AF Pfleiderer, B Moore, A Tokareva, E Ackerman, JL Garrido, L TI Biodegradation of polysiloxanes in lymph nodes of rats measured with Si-29 NMR SO BIOMATERIALS LA English DT Article DE silicon-29 NMR; silicones; biodegradation; lymph nodes ID HUMAN ADJUVANT DISEASE; CONNECTIVE-TISSUE DISEASES; BREAST IMPLANTS; AUGMENTATION MAMMOPLASTY; SILICONE IMPLANTS; SYSTEMIC-SCLEROSIS; MAMMAPLASTY; SCLERODERMA; WOMEN AB Linear and cyclic polysiloxanes and extracts (free polymer) from a silicone gel-filled implant are used to investigate the reactivity of silicones in vivo. Aqueous emulsions of polysiloxanes and controls (without polysiloxanes) are injected once (day 0, similar to 10% w/v) or six times (starting at day 0, every 14 days, similar to 3% w/v) in the right thigh of rats and the popliteal and lumbar lymph nodes are harvested (3 rats per time point and compound investigated) at 2, 16, 30, 44 58 and 72 days after the injection. Si-29 NMR spectroscopy is used to detect and evaluate the presence of polysiloxanes and their metabolites in the lymph nodes. In addition to the resonance associated with the polysiloxane injected(similar to-20 ppm), the NMR spectra of lymph nodes show new resonances that are attributed to partially hydrolyzed polysiloxanes (- 5 to - 15 ppm) and silica (-90 to - 120 ppm). These resonances are not present in polysiloxanes emulsions before injection or in the lymph nodes of controls. Our results demonstrate that all polysiloxanes and extracts from silicone gel-filled implants are biotransformed in the lymph nodes, but high molecular weight polymer degrades at a slower rate than oligomers. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, Biomat Lab, NMR Ctr, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Garrido, L (reprint author), Massachusetts Gen Hosp, Dept Radiol, Biomat Lab, NMR Ctr, Charlestown, MA 02129 USA. RI Garrido, Leoncio/K-3092-2014; Ackerman, Jerome/E-2646-2015 OI Garrido, Leoncio/0000-0002-7587-1260; Ackerman, Jerome/0000-0001-5176-7496 FU NCI NIH HHS [R01 CA 59651] NR 40 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAR PY 1999 VL 20 IS 6 BP 561 EP 571 DI 10.1016/S0142-9612(98)00208-7 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 176XQ UT WOS:000079177800008 PM 10213359 ER PT J AU Lipsitz, SR Ibrahim, JG Fitzmaurice, GM AF Lipsitz, SR Ibrahim, JG Fitzmaurice, GM TI Likelihood methods for incomplete longitudinal binary responses with incomplete categorical covariates SO BIOMETRICS LA English DT Article DE EM algorithm; logistic regression; maximum likelihood estimation; missing data; repeated measures ID MAXIMUM-LIKELIHOOD; REGRESSION-MODELS; EM ALGORITHM AB We consider longitudinal studies in which the outcome observed over time is binary and the covariates of interest, are categorical. With no missing responses or covariates, one specifies a multinomial model for the responses given the covariates and uses maximum likelihood to estimate the parameters. Unfortunately, incomplete data in the responses and covariates are a common occurrence in longitudinal studies. Here we assume the missing data are missing at random (Rubin, 1976, Biometrika 63, 581-592). Since all of the missing data (responses and covariates) are categorical, a useful technique for obtaining maximum likelihood parameter estimates is the EM algorithm by the method of weights proposed in Ibrahim (1990, Journal of the American Statistical Association 85, 765-769). In using the EM algorithm with missing responses and covariates, one specifies thc joint distribution of the responses and covariates. Here we consider the parameters of the covariate distribution as a nuisance. In data sets where the percentage of missing data is high, the estimates of the nuisance parameters can lead to highly unstable estimates of the parameters of interest. We propose a conditional model for the covariate distribution that has several modeling advantages for the EM algorithm and provides a reduction in the number of nuisance parameters, thus providing more stable estimates in finite samples. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lipsitz, SR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. FU NCI NIH HHS [CA 70101-01, CA 57253, CA 55576] NR 13 TC 8 Z9 10 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1999 VL 55 IS 1 BP 214 EP 223 DI 10.1111/j.0006-341X.1999.00214.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 183RK UT WOS:000079567100025 PM 11318157 ER PT J AU Betensky, RA Lindsey, JC Ryan, LM Wand, MP AF Betensky, RA Lindsey, JC Ryan, LM Wand, MP TI Local EM estimation of the hazard function for interval-censored data SO BIOMETRICS LA English DT Article DE EM algorithm; estimating equations; local likelihood ID LIKELIHOOD-ESTIMATION; MAXIMUM-LIKELIHOOD; NONPARAMETRIC-ESTIMATION; QUASI-LIKELIHOOD; REGRESSION; ALGORITHM; MODELS; BOOTSTRAP; BANDWIDTH; SPLINES AB We propose a smooth hazard estimator for interval-censored survival data using the method of local likelihood. The model is fit using a local EM algorithm. The estimator is more descriptive than traditional empirical estimates in regions of concentrated information and takes on a parametric flavor in regions of sparse information. We derive two different standard error estimates for the smooth curve, one based on asymptotic theory and the other on the bootstrap. We illustrate the local EM method for times to breast cosmesis deterioration (Finkelstein, 1986, Biometrics 42, 845-854) and for times to HIV-1 infection for individuals with hemophilia (Kroner et al., 1994, Journal of AIDS 7, 279-286). Our hazard estimates for each of these data sets show interesting structures that would not be found using a standard parametric hazard model or empirical survivorship estimates. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Betensky, RA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009; Wand, Matt /F-9413-2012 OI Ryan, Louise/0000-0001-5957-2490; Wand, Matt /0000-0003-2555-896X FU NCI NIH HHS [CA48061]; NIAID NIH HHS [1U01 AI 41110, 5U01 AI 38855] NR 37 TC 26 Z9 26 U1 2 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1999 VL 55 IS 1 BP 238 EP 245 DI 10.1111/j.0006-341X.1999.00238.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 183RK UT WOS:000079567100028 PM 11318161 ER PT J AU Urbanc, B Cruz, L Buldyrev, SV Havlin, S Irizarry, MC Stanley, HE Hyman, BT AF Urbanc, B Cruz, L Buldyrev, SV Havlin, S Irizarry, MC Stanley, HE Hyman, BT TI Dynamics of plaque formation in Alzheimer's disease SO BIOPHYSICAL JOURNAL LA English DT Article ID AMYLOID PRECURSOR PROTEIN; SENILE PLAQUES; SCAVENGER RECEPTOR; BETA-PROTEIN; DEPOSITION AB Plaques that form in the brains of Alzheimer patients are made of deposits of the amyloid-beta peptide. We analyze the time evolution of amyloid-beta deposition in immunostained brain slices from transgenic mice. We find that amyloid-beta deposits appear in clusters whose characteristic size increases from 14 mu m in 8-month-old mice to 22 mu m in 12-month-old mice. We show that the clustering has implications for the biological growth of amyloid-beta by presenting a growth model that accounts for the experimentally observed structure of individual deposits and predicts the formation of clusters of deposits and their time evolution. C1 Boston Univ, Ctr Polymer Studies, Dept Phys, Boston, MA 02215 USA. Gonda Goldschmied Ctr, Ramat Gan, Israel. Bar Ilan Univ, Dept Phys, Ramat Gan, Israel. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Stanley, HE (reprint author), Boston Univ, Ctr Polymer Studies, Dept Phys, 590 Commonwealth Ave, Boston, MA 02215 USA. RI Urbanc, Brigita/G-5839-2011; Cruz Cruz, Luis/B-2685-2013; Buldyrev, Sergey/I-3933-2015 OI Urbanc, Brigita/0000-0001-9159-7698; FU NIA NIH HHS [AG08487] NR 20 TC 45 Z9 45 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1999 VL 76 IS 3 BP 1330 EP 1334 PG 5 WC Biophysics SC Biophysics GA 173GG UT WOS:000078972300016 PM 10049316 ER PT J AU Oswell, GM Doolittle, MH Reue, K AF Oswell, GM Doolittle, MH Reue, K TI Preparation of YAC end fragments from the Whitehead/MIT mouse YAC library pRML vectors SO BIOTECHNIQUES LA English DT Article ID AMPLIFICATION; GENOME C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Reue, K (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,Bldg 113,Room 312, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL58627, HL28481] NR 7 TC 0 Z9 0 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 1999 VL 26 IS 3 BP 396 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 173MH UT WOS:000078984000006 PM 10090972 ER PT J AU Chauhan, D Bharti, A Raje, N Gustafson, E Pinkus, GS Pinkus, JL Teoh, G Hideshima, T Treon, SP Fingeroth, JD Anderson, KC AF Chauhan, D Bharti, A Raje, N Gustafson, E Pinkus, GS Pinkus, JL Teoh, G Hideshima, T Treon, SP Fingeroth, JD Anderson, KC TI Detection of Kaposi's sarcoma herpesvirus DNA sequences in multiple myeloma bone marrow stromal cells SO BLOOD LA English DT Article ID INFECTION; EXPRESSION; LYMPHOCYTES; SECRETION; PROTEIN; HHV-8; GENES AB Whether Kaposi's sarcoma herpesvirus (KSHV) is associated with multiple myeloma (MM) remains controversial. We assayed for KSHV DNA sequences in long-term bone marrow stromal cells (BMSCs) from 26 patients with MM and 4 normal donors. Polymerase chain reaction (PCR) using primers which amplify a KSHV gene sequence to yield a 233-bp fragment (KS330(233) within open reading frame 26) was negative in all cases. Aliquots of these PGR products were used as templates in subsequent nested PCR, with primers that amplify a 186-bp product internal to KS330(233). BMSCs from 24 of 26 (92%) patients with MM and 1 of 4 normal donors were KSHV PCR+. DNA sequence analyses showed interpatient specific mutations (2 to 3 bp). Both Southern blot and sequence analyses confirmed the specificity of PCR results. The presence of the KSHV gene sequences was further confirmed by amplifying T 1.1 (open reading frame [ORF] K7) and viral cyclin D (ORF 72), two other domains within the KSHV genome. Immunohistochemical studies of KSHV PCR+ MM BMSCs demonstrate expression of dendritic cell (DC) lineage markers (CD68, CD83, and fascin). Serological studies for the presence of KSHV lytic or latent antibodies were performed using sera from 53 MM patients, 12 normal donors, and 5 human immunodeficiency virus (HIV)/KSHV+ patients. No lytic or latent antibodies were present in sera from either MM patients or normal donors. Taken together, these findings show that KSHV DNA sequences are detectable in BMSCs from the majority of MM patients, but that serologic responses to KSHV are not present. Ongoing studies are defining whether the lack of antibody response is caused by the absence of ongoing infection, the presence of a novel viral strain associated with MM, or underlying immunodeficiency in these patients. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA50947, CA78378] NR 35 TC 54 Z9 54 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1999 VL 93 IS 5 BP 1482 EP 1486 PG 5 WC Hematology SC Hematology GA 168TM UT WOS:000078708800006 PM 10029574 ER PT J AU Raje, N Gong, JL Chauhan, D Teoh, G Avigan, D Wu, ZK Chen, DS Treon, SP Webb, IJ Kufe, DW Anderson, KC AF Raje, N Gong, JL Chauhan, D Teoh, G Avigan, D Wu, ZK Chen, DS Treon, SP Webb, IJ Kufe, DW Anderson, KC TI Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi's sarcoma herpesvirus gene sequences SO BLOOD LA English DT Article ID COLONY-STIMULATING-FACTOR; DNA-SEQUENCES; INFECTION; GROWTH; IMMUNIZATION; PROGENITORS; CHILDREN; IMMUNITY; CAPACITY; ALPHA AB Multiple myeloma (MM) cells express idiotypic proteins and other tumor-associated antigens which make them ideal targets for novel immunotherapeutic approaches. However, recent reports show the presence of Kaposi's sarcoma herpesvirus (KSHV) gene sequences in bone marrow dendritic cells (BMDCs) in MM, raising concerns regarding their antigen-presenting cell (APC) function. In the present study, we sought to identity the ideal source of DCs from MM patients for use in vaccination approaches. We compared the relative frequency, phenotype, and function of BMDCs or peripheral blood dendritic cells (PBDCs) from MM patients versus normal donors. DCs were derived by culture of mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. The yield as well as the pattern and intensity of Ag (HLA-DR, CD40, CD54, CD80, and CD86) expression were equivalent on DCs from BM or PB of MM patients versus normal donors. Comparison of PBDCs versus BMDCs showed higher surface expression of HLA-DR (P = .01), CD86 (P = .0003), and CD14 (P = .04) on PBDCs. APC function, assessed using an allogeneic mixed lymphocyte reaction (MLR), demonstrated equivalent T-cell proliferation triggered by MM versus normal DCs. Moreover, no differences in APC function were noted in BMDCs compared with PBDCs. polymerase chain reaction (PCR) analysis of genomic DNA from both MM patient and normal donor DCs for the 233-bp KSHV gene sequence (KS330(233)) was negative, but nested PCR to yield a final product of 186 bp internal to KS330(233) was positive in 16 of 18 (88.8%) MM BMDCs, 3 of 8 (37.5%) normal BMDCs, 1 of 5 (20%) MM PBDCs, and 2 of 6 (33.3%) normal donor PBDCs. Sequencing of 4 MM patient PCR products showed 96% to 98% homology to the published KSHV gene sequence, with patient specific mutations ruling out PCR artifacts or contamination. In addition, KHSV-specific viral cyclin D (open reading frame [ORF] 72) was amplified in 2 of 5 MM BMDCs, with sequencing of the ORF 72 amplicon revealing 91% and 92% homology to the KSHV viral cyclin a sequence. These sequences again demonstrated patient specific mutations, ruling out contamination. Therefore, our studies show that PB appears to be the preferred source of DCs for use in vaccination strategies due to the ready accessibility and phenotypic profile of PBDCs, as well as the comparable APC function and lower detection rate of KSHV gene sequences compared with BMDCs. Whether active KSHV infection is present and important in the pathophysiology of MM remains unclear; however our study shows that MMDCs remain functional despite the detection of KSHV gene sequences. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Singapore Gen Hosp, Dept Hematol, Singapore 0316, Singapore. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02215 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [CA50947, CA98378] NR 56 TC 58 Z9 60 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1999 VL 93 IS 5 BP 1487 EP 1495 PG 9 WC Hematology SC Hematology GA 168TM UT WOS:000078708800007 PM 10029575 ER PT J AU Alyea, EP Canning, C Houde, H Soiffer, RJ Giralt, S Gee, A Champlin, R Atkinson, K AF Alyea, EP Canning, C Houde, H Soiffer, RJ Giralt, S Gee, A Champlin, R Atkinson, K TI CD8 depletion using T8 murine monoclonal antibody-coated dense nickel particles: Efficacy of depletion and safety in donor lymphocyte infusion (DLI). SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Coulter Cellular Therapies, Roxbury, MA USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 1999 VL 23 SU 1 MA 136 BP S43 EP S43 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 183PV UT WOS:000079562900138 ER PT J AU Houde, H Schmittling, R Lu, T Ritz, J Monroy, R AF Houde, H Schmittling, R Lu, T Ritz, J Monroy, R TI A rapid and effective depletion of B cells using CD19 and CD20 monoclonal antibodies coupled to high density microparticles (HDM). SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract C1 Coulter Cellular Therapies Inc, Medford, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 1999 VL 23 SU 1 MA 531 BP S161 EP S161 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 183PV UT WOS:000079562900537 ER PT J AU Urashima, M Teoh, G Akiyama, M Yuza, Y Anderson, KC Maekawa, K AF Urashima, M Teoh, G Akiyama, M Yuza, Y Anderson, KC Maekawa, K TI Restoration of p16(INK4A) protein induces myogenic differentiation in RD rhabdomyosarcoma cells SO BRITISH JOURNAL OF CANCER LA English DT Article DE p16; rhabdomyosarcoma differentiation; cell cycle ID MULTIPLE-MYELOMA; ALVEOLAR RHABDOMYOSARCOMA; CHROMOSOMAL TRANSLOCATION; RETINOBLASTOMA PROTEIN; FAMILIAL MELANOMA; LEUKEMIA; KINASE; EXPRESSION; GROWTH; MUSCLE AB p16(INK4A) (p16) tumour suppressor induces growth arrest by inhibiting function of cyclin-dependent kinase (CDK)4 and CDK6. Homozygous p16 gene deletion is frequent in primary rhabdomyosarcoma (RMS) cells as well as derived cell lines. To confirm the significance of p16 gene deletion in tumour biology of RMS, a temperature-sensitive p16 mutant (E119G) gene was retrovirally transfected into the human RMS cell line RD, which has homozygous gene deletion of p16 gene. Decrease from 40 degrees C (restrictive) to 34 degrees C (permissive) culture temperature reduced CDK6-associated kinase activity and induced G1 growth arrest. Moreover, RD-p16 cells cultured under permissive condition demonstrated differentiated morphology coupled with expressions of myogenin and myosin light chain. These suggest that deletion of p16 gene may not only facilitate growth but also inhibit the myogenic differentiation of RD RMS cells. C1 Jikei Univ, Sch Med, Dept Pediat, Minato Ku, Tokyo 1058461, Japan. Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Urashima, M (reprint author), Jikei Univ, Sch Med, Dept Pediat, Minato Ku, 3-25-8 Nishi-shinbashi, Tokyo 1058461, Japan. NR 30 TC 14 Z9 14 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR PY 1999 VL 79 IS 7-8 BP 1032 EP 1036 DI 10.1038/sj.bjc.6690165 PG 5 WC Oncology SC Oncology GA 168NQ UT WOS:000078699500005 PM 10098732 ER PT J AU Feliers, D Woodruff, K Abboud, S AF Feliers, D Woodruff, K Abboud, S TI Potential role of insulin-like growth factor binding protein-4 in the uncoupling of bone turnover in multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE insulin-like growth factor binding proteins; insulin-like growth factor; myeloma; interferon-gamma; bone turnover ID OSTEOBLAST-LIKE CELLS; MARROW STROMAL CELLS; SMOOTH-MUSCLE CELLS; INTERFERON-GAMMA; FACTOR-I; T-CELLS; PARATHYROID-HORMONE; OSTEOSARCOMA CELLS; GENE-EXPRESSION; RAT AB Decreased bone formation plays an important role in the development of IJ tic lesions during the late stage of multiple myeloma (MM). Release of insulin-like growth factor binding protein-4 (IGFBP4) by tumour cells adjacent to bone may inhibit IGF-I-stimulated osteoblast growth and contribute to decreased bone formation. The present study demonstrates that the human MM cell line, ARH-77, ex-presses IGFBP4 and, to a lesser extent, IGFBP6 mRNA and protein. IGFBP4 expression in myeloma cells may be modulated by cytokines released by stromal cells and T cells in the microenvironment. We tested the effect of recombinant interferon-gamma (INF) an IGFBP4 expression in ARH-77. INF increased IGFBP4 mRNA and protein levels at 12 h, with a decline to baseline by 24 h. In contrast, IGFBP4 was not regulated in response to IL-6, TNF-alpha, PDGF BE, bFGF TGF-beta or the cAMP agonist, forskolin. In other systems, IGFBP4 map also be regulated post-transcriptionally by a protease that is activated by IGF-I or -II. Conditioned medium from ARH-77 cultures incubated with IGF-I or -II for up to 24 h failed to demonstrate proteolytic activity Proteolysis was also not observed when conditioned medium containing exogenous rhIGFBP4 was incubated with IGF-I or -II under cell-free conditions. To determine if human myeloma tumours also express IGFBP4, total RNA was isolated from four tumour biopsies. All samples expressed detectable levels of IGFBP4 mRNA. These findings indicate that interferon-gamma may indirectly modulate bone Formation via the the release of tumour-derived IGFBP4, suggesting that the immune system map influence bone turnover in MM, Failure of myeloma cells to release protease activity may promote IGFBP4 accumulation in the microenvironment during tumour growth. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Abboud, S (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAMS NIH HHS [AR42306] NR 56 TC 14 Z9 16 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 1999 VL 104 IS 4 BP 715 EP 722 DI 10.1046/j.1365-2141.1999.01243.x PG 8 WC Hematology SC Hematology GA 180VH UT WOS:000079405500010 PM 10192430 ER PT J AU Limmroth, V Bischoff, A Yu, X Moskowitz, MA Diener, HC Michel, MC AF Limmroth, V Bischoff, A Yu, X Moskowitz, MA Diener, HC Michel, MC TI Inhibition of neurogenic inflammation by ketoprofen does not involve cyclooxygenase inhibition SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 Univ Essen Gesamthsch, Dept Neurol, Essen, Germany. Univ Essen Gesamthsch, Dept Med, Essen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1999 VL 126 SU S MA 153P BP U82 EP U82 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 185AJ UT WOS:000079645700154 ER PT J AU Butler, CE Yannas, IV Compton, CC Correia, CA Orgill, DP AF Butler, CE Yannas, IV Compton, CC Correia, CA Orgill, DP TI Comparison of cultured and uncultured keratinocytes seeded into a collagen-GAG matrix for skin replacements SO BRITISH JOURNAL OF PLASTIC SURGERY LA English DT Article DE skin replacement; keratinocytes; collagen-GAG; matrix seeding ID ARTIFICIAL SKIN; EPIDERMAL-CELLS; REGENERATION; DESIGN; GROWTH; MODEL; AUTOGRAFTS; DERMIS; GRAFTS; WOUNDS AB A well-characterised collagen-glycosaminoglycan (CG) matrix functions as an extracellular matrix analogue (ECMA) of dermis on full-thickness wounds. The epidermis can be reconstituted by seeding autologous uncultured keratinocytes into the matrix prior to grafting. We hypothesised that seeding the CG matrix with keratinocytes cultured to sub-confluence may provide the ECMA with more proliferating keratinocytes than with uncultured keratinocytes. Autologous cells were isolated from split-thickness skill grafts and cultured to sub-confluence. ECMAs were seeded by centrifuging cultured (n = 8) or uncultured (n = 8) autologous keratinocytes into a CG matrix at a density of 100 000 cells/cm(2), then applied onto full-thickness wounds on Yorkshire pigs. Gross and histologic observations were made up to 21 days post-grafting. At 14 days, a fully differentiated epidermis was present on all graft sites, but the epidermis of the cultured-cell-seeded matrices was thicker, 180 (19) mu m, than the uncultured-cell-seeded matrices, 110 (18) mu m. The epidermis of cultured-cell-seeded matrices was acanthotic, containing 14 (4) cell layers, as compared to uncultured-cell-seeded matrices, 9 (1) cell layers. The number of subepithelial keratinocyte cysts/cm cross-section present in the neodermis was also greater in cultured-, 1.35 (0.37), than in uncultured-cell-seeded matrices, 0.47 (0.35). Epidermal confluence on day 14 was 96 (3)% on cultured-cell-seeded grafts and 50 (17)% on uncultured-cell-seeded grafts. These results are consistent with the hypothesis that the process of in vitro cell cultivation increases the proportion of dividing cells in preference to differentiated cells. This technology may be useful in reconstruction of specialised bilayer tissues with minimal donor sites. C1 Brigham & Womens Hosp, Div Plast Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Burn & Trauma Unit, Boston, MA 02115 USA. MIT, Fibers & Polymers Labs, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Orgill, DP (reprint author), Brigham & Womens Hosp, Div Plast Surg, 75 Francis St, Boston, MA 02115 USA. FU NIGMS NIH HHS [R01 GM50143, GM7560] NR 29 TC 44 Z9 46 U1 0 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-1226 J9 BRIT J PLAST SURG JI Br. J. Plast. Surg. PD MAR PY 1999 VL 52 IS 2 BP 127 EP 132 DI 10.1054/bjps.1997.3047 PG 6 WC Surgery SC Surgery GA 185MQ UT WOS:000079673100010 PM 10434892 ER PT J AU Kalyanasundaram, S Feinstein, S Nicholson, JP Leong, KW Garver, RI AF Kalyanasundaram, S Feinstein, S Nicholson, JP Leong, KW Garver, RI TI Coacervate microspheres as carriers of recombinant adenoviruses SO CANCER GENE THERAPY LA English DT Article DE gene therapy; adenoviridae; microspheres ID PRODUCER CELLS AB The therapeutic utility of recombinant adenoviruses (rAds) is limited in part by difficulties in directing the Viruses to specific sites and by the requirement for bolus administration, both of which limit the efficiency of target tissue infection. As a first step toward overcoming these limitations, rAds were encapsulated in coacervate microspheres comprised of gelatin and alginate followed by stabilization with calcium ions. Ultrastructural evaluation showed that the microspheres formed in this manner were 0.8-10 mu M in diameter, with viruses evenly distributed. The microspheres achieved a sustained release of adenovirus with a nominal loss of bioactivity. The pattern of release and the total amount of virus released was modified by changes in microsphere formulation. Administration of the adenovirus-containing microspheres to human tumor nodules engrafted in mice showed that the viral transgene was transferred to the tumor cells. It is concluded that coacervate microspheres can be used to encapsulate bioactive rAd and release it in a time-dependent manner. C1 Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA. Univ Alabama, Sch Med, Div Pulm & Crit Care Med, Birmingham, AL 35294 USA. Birmingham Vet Affiars Med Ctr, Birmingham, AL 35294 USA. RP Garver, RI (reprint author), 701 S 19th St,LHRB 339, Birmingham, AL 35294 USA. RI Leong, Kam/A-7270-2009 OI Leong, Kam/0000-0002-8133-4955 NR 8 TC 22 Z9 22 U1 0 U2 4 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAR-APR PY 1999 VL 6 IS 2 BP 107 EP 112 DI 10.1038/sj.cgt.7700025 PG 6 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 197XA UT WOS:000080390600002 PM 10195878 ER PT J AU Bruce, JL Chen, CM Xie, Y Zhong, R Wang, YQ Stevenson, MA Calderwood, SK AF Bruce, JL Chen, CM Xie, Y Zhong, R Wang, YQ Stevenson, MA Calderwood, SK TI Activation of heat shock transcription factor 1 to a DNA binding form during the G(1) phase of the cell cycle SO CELL STRESS & CHAPERONES LA English DT Article ID FACTOR-I; SACCHAROMYCES-CEREVISIAE; PROTEIN-SYNTHESIS; HSP70 GENE; EXPRESSION; YEAST; PHOSPHORYLATION; INDUCTION; ASSOCIATE; CLONING AB The heat shock transcription factor (HSF) genes encode proteins that bind to the heat shock elements (HSE) of stress-inducible genes. We have observed the induction of HSF1, the ubiquitous member of the HSF family from a latent cytoplasmic state to a form competent to bind HSE during early G(1) in HeLa cells in the absence of stress. The induction of DNA-binding HSF1 coincided with a burst in cellular protein synthesis in early G(1) and inhibition of this translational peak prevented the formation of DNA binding-activated HSF1. A potential role for HSF1 in cell cycle regulation was suggested by the finding that cell lines stably overexpressing HSF1 showed an increased proportion of G(1) cells relative to other cell cycle phases. However, in contrast to the effects of heat shock, entry into G(1) did not lead to HSF1 hyperphosphorylation or increased activity of a heat shock promoter-reporter gene and did not cause the induction of heat shock protein 70 expression. Thus HSF1, previously implicated in the heat shock response is activated to a DNA binding from in G(1) under non-stress conditions and may play a role in G(1) regulation that does not involve the transcription of heat shock genes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. MGH Canc Ctr, Charlestown, MA 02129 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, JFB 205,44 Binney St, Boston, MA 02115 USA. EM stuart_calderwood@dfci.harvard.edu NR 36 TC 17 Z9 19 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD MAR PY 1999 VL 4 IS 1 BP 36 EP 45 DI 10.1379/1466-1268(1999)004<0036:AOHSTF>2.3.CO;2 PG 10 WC Cell Biology SC Cell Biology GA 185QA UT WOS:000079680000005 PM 10467107 ER PT J AU Reedy, JS Kuhlman, JE Voytovich, M AF Reedy, JS Kuhlman, JE Voytovich, M TI Microvascular pulmonary emboli secondary to precipitated crystals in a patient receiving total parenteral nutrition - A case report and description of the high-resolution CT findings SO CHEST LA English DT Article DE calcium-phosphate crystals; calcium-phosphate product; high-resolution CT; microvascular pulmonary embolism; reticulonodular interstitial infiltrates; total parenteral nutrition ID RENAL-FAILURE; COMPATIBILITY; CALCIUM; PHOSPHATE; HYPERALIMENTATION; COMPLICATION AB A patient with a history of a small-bowel transplant that was subsequently resected required total parenteral nutrition for nutritional supplementation. While receiving therapy he developed chest tightness, shortness of breath, and fever. The chest radiograph showed bilateral reticulonodular opacities, and the high-resolution CT scan demonstrated diffuse, poorly marginated micronodular opacities in a miliary pattern. Pathology specimens obtained by transbronchial biopsy revealed amorphous material obstructing the pulmonary microvasculature. Microvascular emboli secondary to precipitated crystals is a potential complication of total parenteral nutrition. An awareness of the factors that influence crystal solubility may prevent adverse interactions in patients who require parenteral nutrition. C1 Univ Wisconsin Hosp & Clin, Dept Pulm & Crit Care Med, Madison, WI 53792 USA. Univ Wisconsin Hosp & Clin, Dept Surg Pathol, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Reedy, JS (reprint author), Univ Wisconsin Hosp & Clin, Dept Pulm Med, 600 Highland Ave, Madison, WI 53792 USA. EM JS.Reedy@hosp.wisc.edu NR 15 TC 25 Z9 25 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 1999 VL 115 IS 3 BP 892 EP 895 DI 10.1378/chest.115.3.892 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 175TD UT WOS:000079110400054 PM 10084512 ER PT J AU Grinspoon, S Corcoran, C Anderson, E Hubbard, J Stanley, T Basgoz, N Klibanski, A AF Grinspoon, S Corcoran, C Anderson, E Hubbard, J Stanley, T Basgoz, N Klibanski, A TI Sustained anabolic effects of long-term androgen administration in men with AIDS wasting SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY AB Fifty-one human immunodeficiency virus-positive men with hypogonadism and wasting were randomized to receive testosterone enanthate, 300 mg im every 3 weeks, or placebo for 6 months, followed by open-label testosterone administration for 6 months. Subjects initially randomized to placebo gained lean body mass (LBM) only after crossover to testosterone administration (mean change +/- standard error of the mean, -0.6 +/- 0.7 kg [months 0-6] vs, 1.9 +/- 0.7 kg [months 6-12]; P =.03), In contrast, subjects initially randomized to testosterone continued to gain LBM during open-label administration (2.0 +/- 0.7 kg [months 0-6] vs. 1.6 +/- 0.6 kg [months 6-12]; P =.62) and had gained more LBM at 1 year than did subjects receiving testosterone for only the final 6 months of the study (3.7 +/- 0.8 kg vs. 1.0 1.0 kg; P =.05). Testosterone administration results in sustained increases in LBM during 1 year of therapy in hypogonadal men with AIDS wasting. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Infect Dis Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR01066]; NIDDK NIH HHS [R01-DK49302, P32-DK07028] NR 9 TC 26 Z9 26 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1999 VL 28 IS 3 BP 634 EP 636 DI 10.1086/515162 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175RZ UT WOS:000079110000035 PM 10194091 ER PT J AU Malanga, CJ Kosofsky, BE AF Malanga, CJ Kosofsky, BE TI Mechanisms of action of drugs of abuse on the developing fetal brain SO CLINICS IN PERINATOLOGY LA English DT Review ID PRENATAL ALCOHOL EXPOSURE; CONDITIONED PLACE PREFERENCE; REGULATED GENE-EXPRESSION; TRANSPORTER KNOCKOUT MICE; COCAINE-SEEKING BEHAVIOR; DEVELOPING MURINE BRAIN; DEVELOPING RAT-BRAIN; CANNABINOID RECEPTOR; NUCLEUS-ACCUMBENS; MESOLIMBIC DOPAMINE AB The consequences of public health of the acquisition and use of drugs of abuse have been well demonstrated. Despite intense however, progress has been slow in recent years in ascertaining the specific neurodevelopmental effects of these drugs on the children of drug-abusing mothers. The use of animal models allows the investigator to determine the specific biological contributions of prenatal exposure to drugs of abuse on neurodevelopmental outcome while controlling for covariates that have confounded clinical studies, such as altered nutrition in pregnancy, suboptimal rearing environment of the young, and availability of drug and nondrug stimulation to the offspring. This article selectively reviews the preclinical literature on the gestational effects of drugs of abuse with particular emphasis on cocaine, ethanol, and the opiate narcotics, Mechanisms of drug action on the mature and developing brain are summarized. A model of developmental impact on the brain regions underlying drug-induced reward and reinforcement and its potential postnatal importance is presented. C1 Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kosofsky, BE (reprint author), Massachusetts Gen Hosp E, Lab Mol & Dev Neurosci, 149 13th St, Charlestown, MA 02129 USA. EM kosofsky@helix.mgh.harvard.edu OI Malanga, C.J./0000-0003-4808-3995 FU NIDA NIH HHS [K02DA00354] NR 120 TC 57 Z9 58 U1 1 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD MAR PY 1999 VL 26 IS 1 BP 17 EP + PG 23 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 185TJ UT WOS:000079686200004 PM 10214541 ER PT J AU Laeng, B Kosslyn, SM Caviness, VS Bates, J AF Laeng, B Kosslyn, SM Caviness, VS Bates, J TI Can deficits in spatial indexing contribute to simultanagnosia? SO COGNITIVE NEUROPSYCHOLOGY LA English DT Review ID EYE-MOVEMENT CONTROL; VISUAL-SEARCH; FEATURE-INTEGRATION; LETTER RECOGNITION; FOCUSED ATTENTION; BALINTS-SYNDROME; PERCEPTION; INFORMATION; VISION; MODEL AB Patient AMA suffered a head trauma that left her with several visual complaints, including a reading disability. AMA appears to suffer from 'simultanagnosia, as established with tasks such as naming briefly presented multiple stimuli or overlapping figures, describing the theme of complex scenes, and counting arrays of stimuli. Specifically, AMA has difficulty perceiving immediately successive stimuli and, in particular, multiple stimuli that appear at novel or unexpected locations. Her ability to encode spatial relations rapidly (of either the categorical and coordinate type) is markedly reduced. However, when a familiar target appears among multiple stimuli at expected (previously encoded) locations, AMA's performance can be within normal limits. These results suggest that this patient's simultanagnosia cannot be reduced to an inability to process multiple stimuli per se. Rather it is better characterised as (1) an inability to index new locations of multiple stimuli, and (2) a reduced efficiency in pattern analysis. The former deficit, in turn, may lead to difficulty in focusing on objects efficiently and using objects as landmarks or reference points. Damage to one or both of the above mechanisms could produce simultanagnosia and reading difficulty. C1 Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cambridge, MA USA. RP Laeng, B (reprint author), Univ Tromso, Dept Psychol, Asgardveien 9, N-9037 Tromso, Norway. EM bruno@psyk.uit.no NR 125 TC 8 Z9 8 U1 1 U2 1 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0264-3294 J9 COGN NEUROPSYCHOL JI Cogn. Neuropsychol. PD MAR PY 1999 VL 16 IS 2 BP 81 EP 114 DI 10.1080/026432999380915 PG 34 WC Psychology; Psychology, Experimental SC Psychology GA 177FZ UT WOS:000079201100001 ER PT J AU Berti, JJ Sharata, HH AF Berti, JJ Sharata, HH TI Metastatic basal cell carcinoma to the lung SO CUTIS LA English DT Article AB Basal cell carcinoma is a relatively common tumor with an increasing incidence. Despite this, metastatic disease is an extremely rare event. A review of metastatic basal cell carcinoma is presented. C1 Univ Wisconsin, Hosp & Clin Fdn, Dermatol Clin, Univ Stn Clin, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Hosp, Serv Dermatol, Madison, WI USA. RP Sharata, HH (reprint author), Univ Wisconsin, Hosp & Clin Fdn, Dermatol Clin, Univ Stn Clin, 2880 Univ Ave, Madison, WI 53705 USA. NR 12 TC 10 Z9 11 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0011-4162 J9 CUTIS JI Cutis PD MAR PY 1999 VL 63 IS 3 BP 165 EP 166 PG 2 WC Dermatology SC Dermatology GA 179AJ UT WOS:000079301100012 PM 10190068 ER PT J AU Eaglstein, WH Alvarez, OM Auletta, M Leffel, D Rogers, GS Zitelli, JA Norris, JEC Thomas, I Irondo, M Fewkes, J Hardin-Young, J Duff, RG Sabolinski, ML AF Eaglstein, WH Alvarez, OM Auletta, M Leffel, D Rogers, GS Zitelli, JA Norris, JEC Thomas, I Irondo, M Fewkes, J Hardin-Young, J Duff, RG Sabolinski, ML TI Acute excisional wounds treated with a tissue-engineered skin (Apligraf) SO DERMATOLOGIC SURGERY LA English DT Article ID Y-CHROMOSOME; SURVIVAL AB BACKGROUND. Tissue-engineered products are usually composed of living cells and their supporting matrices that have been grown in vitro, using a combination of engineering and life sciences principles. Apligraf is a bilayered product composed of neonatal-derived dermal fibroblasts and keratinocytes, and Type I bovine collagen. OBJECTIVE. To evaluate in a prospective, multicentered open study, the effects of tissue therapy with a tissue-engineered skin (Apligraf) with partial or full-thickness excisional wounds. METHODS. One hundred and seven patients participated in this study. The tissue-engineered skin was applied once, immediately after excisional surgery, usually for skin cancer, and patients were followed for up to one year. RESULTS. The safety results were impressive, with no clinical or laboratory evidence of rejection. Clinically, graft persistence was good to excellent in 77 of 105 (73.3%) of patients at one week, falling to 56.6% and 53.6% at two weeks and one month respectively. CONCLUSION. To date, this is the largest experience with a tissue-engineered skin product in acute wounds, and this study suggests that tissue therapy may be safe and useful. C1 Univ Miami, Sch Med, Dept Dermatol & Cutaneous Surg, Miami, FL 33101 USA. Univ Wound Healing Clin, New Brunswick, NJ USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Dermatol, New Brunswick, NJ USA. Yale Univ, Sch Med, Dept Dermatol, New Haven, CT 06510 USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Organogenesis Inc, Canton, MA USA. RP Eaglstein, WH (reprint author), Univ Miami, Dept Dermatol, POB 016250 R-250, Miami, FL 33101 USA. NR 9 TC 83 Z9 90 U1 0 U2 7 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAR PY 1999 VL 25 IS 3 BP 195 EP 201 DI 10.1046/j.1524-4725.1999.08186.x PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 177EU UT WOS:000079197600014 PM 10193966 ER PT J AU Ghiani, CA Eisen, AM Yuan, XQ DePinho, RA McBain, CJ Gallo, V AF Ghiani, CA Eisen, AM Yuan, XQ DePinho, RA McBain, CJ Gallo, V TI Neurotransmitter receptor activation triggers p27(Kip1) and p21(CIP1) accumulation and G(1) cell cycle arrest in oligodendrocyte progenitors SO DEVELOPMENT LA English DT Article DE norepinephrine; O-2A cells; glia; cyclin kinase inhibitors; glutamate receptors; cAMP; voltage-dependent K+ channels ID DEPENDENT KINASE INHIBITOR; BETA-ADRENERGIC RECEPTORS; CENTRAL-NERVOUS-SYSTEM; POSTNATAL RAT FOREBRAIN; MOUSE FETAL DEVELOPMENT; GLIAL PRECURSOR CELLS; CHANNEL EXPRESSION; PRIMARY CULTURES; OPTIC-NERVE; SUBVENTRICULAR ZONE AB We examined the pathways that link neurotransmitter receptor activation and cell cycle arrest in oligodendrocyte progenitors, We had previously demonstrated that glutamate receptor activation inhibits oligodendrocyte progenitor proliferation and lineage progression. Here, using purified oligodendrocyte progenitors and cerebellar slice cultures, we show that norepinephrine and the beta-adrenergic receptor agonist isoproterenol also inhibited the proliferation, but in contrast to glutamate, isoproterenol stimulated progenitor lineage progression, as determined by O4 and O1 antibody staining, This antiproliferative effect was specifically attributable to a beta-adrenoceptor-mediated increase in cyclic adenosine monophosphate, since analogs of this cyclic nucleotide mimicked the effects of isoproterenol on oligodendrocyte progenitor proliferation, while alpha-adrenoceptor agonists were ineffective. Despite the opposite effects on lineage progression, both isoproterenol and the glutamate receptor agonist kainate caused accumulation of the cyclin-dependent kinase inhibitors p27(Kip1) and p21(CIP1), and G(1) arrest, Studies with oligodendrocyte progenitor cells from INK4a(-/-) mice indicated that the G(1) cyclin kinase inhibitor p16(INK4a) as well as p19(ARF) were not required for agonist-stimulated proliferation arrest. Our results demonstrate that beta-adrenergic and glutamatergic receptor activation inhibit oligodendrocyte progenitor proliferation through a mechanism that may involve p27(Kip1) and p21(CIP1); but while neurotransmitter-induced accumulation of p27(Kip1) is associated with cell cycle arrest, it does not by itself promote oligodendrocyte progenitor differentiation. C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gallo, V (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. EM vgallo@helix.nih.gov OI Ghiani, Cristina/0000-0002-9867-6185 NR 84 TC 75 Z9 77 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 1999 VL 126 IS 5 BP 1077 EP 1090 PG 14 WC Developmental Biology SC Developmental Biology GA 180UJ UT WOS:000079403300022 PM 9927607 ER PT J AU Malicki, J Driever, W AF Malicki, J Driever, W TI oko meduzy mutations affect neuronal patterning in the zebrafish retina and reveal cell-cell interactions of the retinal neuroepithelial sheet SO DEVELOPMENT LA English DT Article DE retina; mutant; pattern; oko meduzy; ome; zebrafish; neuroepithelium ID DANIO-RERIO; N-CADHERIN; VERTEBRATE RETINA; EPITHELIAL-CELLS; HORIZONTAL CELLS; PERINATAL DEATH; NEURAL RETINA; MOUSE RETINA; DIFFERENTIATION; GENE AB Mutations of the oko meduzy (ome) locus cause drastic neuronal patterning defect in the zebrafish retina. The precise, stratified appearance of the wild-type retina is absent in the mutants. Despite the lack of lamination, at least seven retinal cell types differentiate in oko meduzy. The ome phenotype is already expressed in the retinal neuroepithelium affecting morphology of the neuroepithelial cells, Our experiments indicate that previously unknown cell-cell interactions are involved in development of the retinal neuroepithelial sheet. In genetically mosaic animals, cell-cell interactions are sufficient to rescue the phenotype of oko meduzy retinal neuroepithelial cells. These cell-cell interactions may play a critical role in the patterning events that lead to differentiation of distinct neuronal laminae that lead in vertebrate retina. C1 Massachusetts Gen Hosp East, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Malicki, J (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM jarema_malicki@meei.harvard.edu RI malicki, jarema/G-8611-2014 FU NICHD NIH HHS [R01 HD29761]; NIMH NIH HHS [R01 MH56552] NR 62 TC 78 Z9 78 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 1999 VL 126 IS 6 BP 1235 EP 1246 PG 12 WC Developmental Biology SC Developmental Biology GA 184PW UT WOS:000079622400014 PM 10021342 ER PT J AU Sharma, A Zangen, DH Reitz, P Taneja, M Lissauer, ME Miller, CP Weir, GC Habener, JF Bonner-Weir, S AF Sharma, A Zangen, DH Reitz, P Taneja, M Lissauer, ME Miller, CP Weir, GC Habener, JF Bonner-Weir, S TI The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration SO DIABETES LA English DT Article ID INSULIN GENE-TRANSCRIPTION; BETA-CELL LINE; ENDOCRINE PANCREAS; POLYPEPTIDE GENE; MESSENGER-RNA; EXPRESSION; GLUCOSE; RAT; BINDING; DIFFERENTIATION AB Islet duodenal homeobox 1 (IDX-1/IPF-1/STF-1/PDX-1), a homeodomain protein that transactivates the insulin promoter, has been shown by targeted gene ablation to be required for pancreatic development. After 90% pancreatectomy (Px), the adult pancreas regenerates in a process recapitulating embryonic development, starting with a burst of proliferation in the epithelium of the common pancreatic duct. In this model, IDX-1 mRNA was detected by semiquantitative reverse transcription-polymerase chain reaction in total RNA from isolated common pancreatic ducts at levels 10% of those of isolated islets. The IDX-1 mRNA levels were not significantly different for common pancreatic ducts of Pr, sham Pr, and unoperated rats and did not change with time after surgery. By immunoblot analysis, IDX-1 protein was only faintly detected in these ducts 1 and 7 days after Pr or sham Pr but was easily detected at 2 and 3 days after Pr. Similarly, IDX-1 immunostaining was barely detectable in sham or unoperated ducts but was strong in ducts at 2-3 days after Pr. The increase of IDX-1 immunostaining followed that of BrdU incorporation (proliferation). These results indicate a posttranscriptional regulation of the IDX-1 expression in ducts. In addition, islets isolated 3-7 days after Pr showed higher IDX-1 protein expression than control islets. Thus, in pancreatic regeneration IDX-1 is upregulated in newly divided ductal cells as well as in islets. The timing of enhanced expression of IDX-1 implies that IDX-1 is not important in the initiation of regeneration but may be involved in the differentiation of ductal cells to beta-cells. C1 Joslin Diabet Ctr, EP Joslin Res Labs, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pediat Endocrinol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Inst Genet, EGRP Grp, Cambridge, MA USA. RP Bonner-Weir, S (reprint author), Joslin Diabet Ctr, EP Joslin Res Labs, 1 Joslin Pl, Boston, MA 02215 USA. EM bonners@joslab.harvard.edu OI Lissauer, Matthew/0000-0002-6008-9778 FU NIDDK NIH HHS [DK-44523, DK-36836] NR 54 TC 263 Z9 273 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 1999 VL 48 IS 3 BP 507 EP 513 DI 10.2337/diabetes.48.3.507 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 170VE UT WOS:000078827100009 PM 10078550 ER PT J AU Bektas, A Warram, JH White, MF Krolewski, AS Doria, A AF Bektas, A Warram, JH White, MF Krolewski, AS Doria, A TI Exclusion of insulin receptor substrate 2 (IRS-2) as a major locus for early-onset autosomal dominant type 2 diabetes SO DIABETES LA English DT Article ID PHOSPHOTYROSINE PROTEIN; LINKAGE ANALYSIS; HUMAN GENOME; GENE; MELLITUS; MEMBER; FAMILY; MAP AB We investigated whether variability at the insulin receptor substrate (IRS)-2 lotus plays a role in the etiology of early-onset autosomal dominant type 2 diabetes. By means of radiation hybrid mapping, Re placed the human IRS-2 gene on 13q at 8.6 cRays from SHGC-37358. Linkage between diabetes and two polymorphic markers located in this region (D13S285 and D13S1295) was then evaluated in 29 families with early-onset autosomal dominant type 2 diabetes. Included were 220 individuals with diabetes, impaired glucose tolerance, or gestational diabetes (mean age at diabetes diagnosis 36 +/- 17 years) and 146 nondiabetic subjects. Overall, strongly negative logarithm of odds (LOD) scores for Linkage with diabetes were obtained by multipoint parametric analysis (LOD score -45.4 at D13S285 and -40.9 at D13S1295), No significant evidence of linkage was obtained under the hypothesis of heterogeneity or by nonparametric methods. Fourteen pedigrees for which linkage could not be excluded (LOD score > -2.0) were screened for mutations in the IRS-2 coding region by dideoxy fingerprinting. However, no mutations segregating with diabetes could be detected in these families. These data indicate that IRS-2 is not a major gene for early-onset autosomal dominant type 2 diabetes, although a role of mutations in the promoter region cannot be excluded at this time. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Renal, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Mol Physiol, Div Renal, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Renal, 1 Joslin Pl, Boston, MA 02215 USA. EM adoria@joslin.harvard.edu FU NIDDK NIH HHS [DK-47475, DK-55523, DK-36836] NR 22 TC 27 Z9 27 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 1999 VL 48 IS 3 BP 640 EP 642 DI 10.2337/diabetes.48.3.640 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 170VE UT WOS:000078827100028 PM 10078569 ER PT J AU Ramsey, SD Sandhu, N Newton, K Reiber, GE Blough, D Wagner, EH McCullough, DK AF Ramsey, SD Sandhu, N Newton, K Reiber, GE Blough, D Wagner, EH McCullough, DK TI Incidence, outcomes, and cost of foot ulcers in patients with diabetes SO DIABETES CARE LA English DT Article ID LOWER-EXTREMITY AMPUTATIONS; RISK-FACTORS; LEG ISCHEMIA; CARE; MELLITUS; PREVENTION; POPULATION; DISEASE; QUALITY AB OBJECTIVE - To determine the incidence of foot ulcers in a large cohort of patients with diabetes, the risk of developing serious complications after diagnosis, and the attributable cost of care compared with that in patients without foot ulcers. RESEARCH DESIGN AND METHODS - Retrospective cohort study of patients with diabetes in a large staff-model health maintenance organization from 1993 to 1995. Patients with diabetes were identified by algorithm using administrative, laboratory and pharmacy records. The data were used to calculate incidence of foot ulcers, risk of osteomyelitis, amputation, and death after diagnosis of foot ulcer, and attributable costs in foot ulcer patients compared with patients without foot ulcers. RESULTS - Among 8,905 patients identified with type 1 or type 2 diabetes, 514 developed a foot ulcer over 3 years of observation (cumulative incidence 5.8%). On or after the time of diagnosis, 77 (15%) patients developed osteomyelitis and 80 (15.6%) required amputation. Survival at 3 years was 72% for the foot ulcer patients venus 87% for a group of age- and sex-matched diabetic patients without foot ulcers (P < 0.001). The attributable cost for a 40- to 65-year-old male with a new foot ulcer was $27,987 for the 2 years after diagnosis. CONCLUSIONS - The incidence of foot ulcers in this cohort of patients with diabetes was nearly 2.0% per year. For those who developed ulcers, morbidity, mortality, and excess care costs were substantial compared with those for patients without foot ulcers. The results appear to support the value of foot-ulcer prevention programs for patients with diabetes. C1 Univ Washington, Clin Econ Cost & Outcomes Res Ctr, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98121 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Ramsey, SD (reprint author), Univ Washington, Clin Econ Cost & Outcomes Res Ctr, Dept Med, Box 358853, Seattle, WA 98195 USA. NR 33 TC 493 Z9 510 U1 4 U2 44 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 1999 VL 22 IS 3 BP 382 EP 387 DI 10.2337/diacare.22.3.382 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 170LD UT WOS:000078806400002 PM 10097914 ER PT J AU Kahn, CR AF Kahn, CR TI Diabetes: a strategic plan for the 21st century SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Editorial Material C1 Harvard Univ, Sch Med, Diabet Res Working Grp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Joslin Clin, Cambridge, MA 02138 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Diabet Res Working Grp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1520-7552 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD MAR-APR PY 1999 VL 15 IS 2 BP 152 EP 155 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 202FC UT WOS:000080640600009 PM 10362463 ER PT J AU Malecki, MT Yang, Y Antonellis, A Curtis, S Warram, JH Krolewski, AS AF Malecki, MT Yang, Y Antonellis, A Curtis, S Warram, JH Krolewski, AS TI Identification of new mutations in the hepatocyte nuclear factor 4 alpha gene among families with early onset Type 2 diabetes mellitus SO DIABETIC MEDICINE LA English DT Article DE genetics; hepatocyte nuclear factor-4 alpha; MODY ID MISSENSE MUTATION; BINDING-SITE; YOUNG MODY1; GLUCOKINASE; PROMOTER; PEDIGREE AB Aims Mutations in hepatocyte nuclear factor (HNF)-4 alpha gene located on chromosome 20q have been found to be responsible for the development of early onset Type 2 diabetes mellitus (DM). Through a national campaign, 53 families with autosomal dominant, early onset Type 2 DM (n=654) were assembled to determine the frequency of mutations in the HNF-4 alpha gene and their contribution to the development of diabetes. Methods Twelve exons and the promoter region of the HNF-4 alpha gene were screened in probands of the families by a double gradient, denaturing gradient gel electrophoresis (DG-DGGE) protocol combined with automated bi-directional sequencing of the PCR products of all heterozygous individuals. Results We detected two new mutations in the HNF-4 alpha gene that changed the amino-acid sequence. The first mutation was a Gly-->Ser substitution in codon 115 within a highly conserved DNA binding domain, and all six carriers of this mutation had diabetes and low insulin secretion. The second mutation was an Ile-->Val substitution in codon 454 within the transactivation domain. It was carried by four family members, two of whom also carried a mutation in the HNF-1 alpha gene. Of those having only the mutation in HNF-4 alpha one had diabetes and the other had normal glucose tolerance and both were obese and hyperinsulinaemic. Thus, it is uncertain that this mutation is responsible for any of the diabetes in this family. Conclusion We have found that mutations in the HNF-4 alpha gene account for a small proportion, about 2-4%, of families with early onset, autosomal dominant, Type 2 DM in US Caucasians. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl,Room 305, Boston, MA 02215 USA. EM Akrolewski@joslin.harvard.edu FU NIDDK NIH HHS [DK-36836, DK-47475] NR 24 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAR PY 1999 VL 16 IS 3 BP 193 EP 200 DI 10.1046/j.1464-5491.1999.00073.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181DV UT WOS:000079426200003 PM 10227563 ER PT J AU Horner, MD AF Horner, MD TI Attentional functioning in abstinent cocaine abusers SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine; neuropsychology; attention; cognition ID NEUROPSYCHOLOGICAL DEFICITS; DEPENDENT PATIENTS; BRAIN PERFUSION; REACTION-TIME; ALCOHOL; IMPAIRMENT; SPECT AB The effect of chronic cocaine use on attention is directly relevant to the treatment of cocaine dependence, since attention underlies most other cognitive processes, and thus the ability to profit from cognitively-based interventions. This paper reviews 17 studies examining attention in patients with cocaine abuse or dependence. Findings have been inconsistent, largely due to various methodological difficulties. There has been some suggestion of reduced cognitive speed, while focused and sustained attention have generally been unimpaired. Divided attention has been largely unexplored. Thus, there is insufficient evidence either to accept or reject the hypothesis of attentional dysfunction associated with chronic cocaine use. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. RP Horner, MD (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave, Charleston, SC 29425 USA. EM hornermd@musc.edu NR 75 TC 32 Z9 34 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 1999 VL 54 IS 1 BP 19 EP 33 DI 10.1016/S0376-8716(98)00141-0 PG 15 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 169DE UT WOS:000078731600003 PM 10101614 ER PT J AU Wang, PH Almahfouz, A Giorgino, F McCowen, KC Smith, RJ AF Wang, PH Almahfouz, A Giorgino, F McCowen, KC Smith, RJ TI In vivo insulin signaling in the myocardium of streptozotocin-diabetic rats: Opposite effects of diabetes on insulin stimulation of glycogen synthase and c-Fos SO ENDOCRINOLOGY LA English DT Article ID KINASE DOMAIN AUTOPHOSPHORYLATION; RECEPTOR SUBSTRATE FAMILY; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOTYROSINE PROTEIN; SKELETAL-MUSCLE; HEART MUSCLE; FATTY-ACIDS; GLUCOSE; RESISTANCE; TRANSPORT AB Diabetes induced by streptozotocin (STZ) in laboratory rats leads to impaired glucose metabolism in the heart and changes in myocardial contractile protein isoform expression and cardiac function. The purpose of this study was to investigate in vivo insulin signaling responses in the myocardium of STZ-diabetic rats. Insulin rapidly stimulated tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1) and, to a lesser extent, IRS-8 in normal and diabetic myocardium. In diabetic rats, there was 2-fold higher insulin receptor content and insulin-stimulated receptor tyrosine phosphorylation in comparison with control rats. IRS-1 tyrosine phosphorylation also increased in STZ diabetes in spite of a decrease in IRS-1 content, resulting in a 4-fold higher ratio of phosphorylated to total IRS-1. This was associated with 2-fold higher IRS-1 precipitable phosphatidylinositide 3-kinase activity in diabetic animals. Insulin stimulation of glycogen synthase activity was significantly diminished in STZ diabetes, consistent with resistance to insulin in a step downstream from phosphatidylinositide 3-kinase activation. Under the same experimental conditions, there was a marked increase in insulin stimulation of myocardial c-fos messenger RNA content in diabetic animals in comparison with controls. These data demonstrate altered early steps in insulin signaling in STZ-diabetic rat myocardium. Consequent oppositely directed disturbances in growth regulatory and glucose regulatory responses to insulin may contribute to the development of myocardial functional abnormalities in this model of diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Smith, RJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM smithr@joslab.harvard.edu RI Giorgino, Francesco/K-7262-2016 OI Giorgino, Francesco/0000-0001-7372-2678 FU NIDDK NIH HHS [DK-43038, DK-36836, DK-48503] NR 49 TC 22 Z9 23 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1999 VL 140 IS 3 BP 1141 EP 1150 DI 10.1210/en.140.3.1141 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169EC UT WOS:000078733700017 PM 10067837 ER PT J AU Shomali, ME Katznelson, L AF Shomali, ME Katznelson, L TI Medical therapy for gonadotroph and thyrotroph tumors SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID SECRETING PITUITARY-ADENOMAS; FOLLICLE-STIMULATING-HORMONE; SOMATOSTATIN ANALOG OCTREOTIDE; SERUM ALPHA-SUBUNIT; GROWTH-HORMONE; GLYCOPROTEIN HORMONE; BETA-SUBUNIT; FOLLOW-UP; INAPPROPRIATE SECRETION; BROMOCRIPTINE TREATMENT AB Gonadotroph adenomas, a common type of pituitary tumor, are not associated with syndromes of hormonal hypersecretion and thus present as pituitary macroadenomas with mass effects, or as incidentally discovered pituitary masses. When indicated, primary therapy is neurosurgery, but there may be a limited role for medical therapy in patients with residual disease. Thyrotroph adenomas are rare neoplasms that present with hyperthyroidism and local mass effects. Medical therapy may be effective in controlling tumor growth and in achieving euthyroidism, when surgery or radiation, or both, do not control the tumor. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Katznelson, L (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,55 Fruit St, Boston, MA 02114 USA. NR 103 TC 19 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD MAR PY 1999 VL 28 IS 1 BP 223 EP + DI 10.1016/S0889-8529(05)70065-7 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 182EY UT WOS:000079486900012 PM 10207693 ER PT J AU Ko, CW Lee, SP AF Ko, CW Lee, SP TI Gallstone formation - Local factors SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID CHOLESTEROL CRYSTAL NUCLEATION; GUINEA-PIG GALLBLADDER; BILIARY ALPHA(1)-ACID GLYCOPROTEIN; TOTAL PARENTERAL-NUTRITION; APOLIPOPROTEIN-E POLYMORPHISM; LONG-TERM TREATMENT; MODEL BILE; PRAIRIE DOG; EPITHELIAL-CELLS; CALCIUM-BINDING AB Supersaturation of bile is a necessary prerequisite to gallstone formation. However, patients who have undergone a cholecystectomy do not form gallstones. This indicates a role of local factors in gallstone formation. Gallbladder stasis, mucin secretion, the presence of pronucleating and antinucleating biliary proteins, and some medications have been shown to alter gallstone formation. New data has also caused the role of bacterial infection in gallstone pathogenesis to be re-examined. in addition, genetic factors have recently been identified which may predispose to gallstone formation by altering the secretion of hepatic bile. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med 111 GI A, Div Gastroenterol, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Lee, SP (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med 111 GI A, Div Gastroenterol, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK 46890, DK 41678] NR 130 TC 34 Z9 36 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD MAR PY 1999 VL 28 IS 1 BP 99 EP + DI 10.1016/S0889-8553(05)70045-5 PG 19 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 184XU UT WOS:000079639700006 PM 10198780 ER PT J AU Jensen, DM AF Jensen, DM TI Career development in endoscopic research: current status and recommendations SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT NIH Workshop on Endoscopic Research Priorities CY DEC 12-13, 1998 CL BETHESDA, MARYLAND SP NIH C1 Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA USA. RP Jensen, DM (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Bldg 115,Rm 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 1999 VL 49 IS 3 BP S100 EP S104 DI 10.1016/S0016-5107(99)70538-9 PN 2 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 174YQ UT WOS:000079064500025 PM 10049461 ER PT J AU Huang, TS Elias, ER Mulliken, JB Kirse, DJ Holmes, LB AF Huang, TS Elias, ER Mulliken, JB Kirse, DJ Holmes, LB TI A new syndrome: Heart defects, laryngeal anomalies, preaxial polydactyly, and colonic aganglionosis in sibs SO GENETICS IN MEDICINE LA English DT Article ID ENDOTHELIN-B RECEPTOR; HIRSCHSPRUNG DISEASE; CLEFT-LIP; MUTATIONS; HYPERTELORISM; EXPRESSION; PALATE AB We present two siblings, one male and one female, who have heart defects, duplication of toes, airway anomalies, and aganglionosis. The brother also has a bilateral complete cleft lip and palate. His airway anomalies include short epiglottis and aryepiglottic folds, which are different from his sister who has a bifid epiglottis with a central epiglottic mass. Both siblings have had some developmental delay. This constellation of anomalies appears to be unique and may represent a new autosomal recessive disorder. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Teratol Unit,Pediat Serv, Boston, MA 02114 USA. Childrens Hosp, Div Genet & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Coordinated Care Serv, Boston, MA 02115 USA. Childrens Hosp, Div Plast Surg, Boston, MA 02115 USA. Univ Kansas, Med Ctr, Dept Otolaryngol, Kansas City, KS 66103 USA. RP Holmes, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Teratol Unit,Pediat Serv, Warren 801, Boston, MA 02114 USA. FU NIGMS NIH HHS [T32GM07748] NR 22 TC 44 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAR-APR PY 1999 VL 1 IS 3 BP 104 EP 108 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 238HG UT WOS:000082704400008 PM 11336448 ER PT J AU Alvarado-Cabrero, I Young, RH Vamvakas, EC Scully, RE AF Alvarado-Cabrero, I Young, RH Vamvakas, EC Scully, RE TI Carcinoma of the fallopian tube: A clinicopathological study of 105 cases with observations on staging and prognostic factors SO GYNECOLOGIC ONCOLOGY LA English DT Article DE fallopian tube; carcinoma; prognostic factors; FIGO staging ID TRANSITIONAL-CELL-CARCINOMA; ENDOMETRIOID CARCINOMA; RETROSPECTIVE ANALYSIS; ADENOCARCINOMA; TUMORS; EPITHELIUM; PATTERN; CANCER; OVARY; LIGHT AB One hundred five cases of carcinoma of the fallopian tube were subjected to a clinicopathological study to investigate the validity of various prognostic factors. A higher stage of tumor, an absence of closure of the fimbriated end of the tube, and an age of 66 years or older were the major predictors of a shorter length of recurrence-free postoperative survival in a univariate analysis. In a multivariate analysis, however, stage was a highly significant prognostic factor, absence of fimbriated-end closure, marginally significant, and older age, not significant. Within Stage I cases the presence or absence of invasion of the tubal wall, the depth of invasion when present, and the location of the tumor within the tube (fimbrial or nonfimbrial) appeared to be prognostically important. These findings strongly suggest that the FIGO staging system should be expanded to permit staging of noninvasive tubal carcinomas and fimbrial carcinomas, which cannot be staged according to the current system, and that depth of invasion of the tubal wall merits future investigation as an additional prognostic factor. (C) 1999 Academic Press. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alvarado-Cabrero, I (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NR 42 TC 106 Z9 108 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 1999 VL 72 IS 3 BP 367 EP 379 DI 10.1006/gyno.1998.5267 PG 13 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 174CE UT WOS:000079015900016 PM 10053109 ER PT J AU Kommoss, F Schmidt, M Merz, E Knapstein, PG Young, RH Scully, RE AF Kommoss, F Schmidt, M Merz, E Knapstein, PG Young, RH Scully, RE TI Ovarian endometrioid-like yolk sac tumor treated by surgery alone, with recurrence at 12 years SO GYNECOLOGIC ONCOLOGY LA English DT Article ID GERM-CELL TUMORS AB We describe the case of a stage Ia endometrioid-like yolk sac tumor (YST) of the ovary, which was originally misdiagnosed as a malignant struma ovarii and not treated with adjuvant chemotherapy. After 12 years, a contralateral dermoid cyst was excised along with a small omental nodule of partially necrotic and calcified endometrioid-like YST. No tumor was detected in several other biopsy specimens, and a peritoneal lavage was negative for tumor cells. Since there was no evidence of remaining tumor and the serum a-fetoprotein (AFP) level was normal after the second operation, the patient was followed, Serial serum AFP levels remained normal for 4 months. At a second-look laparotomy after 4 months, a small tumor nodule was removed from the cul-de-sac. Postoperatively, the patient received three cycles of BEP chemotherapy. The long disease-free interval after the first operation in spite of the presence of occult spread to the omentum and to the pouch of Douglas in this case indicates that some endometrioid-like YSTs may have an indolent course. The present case under-scores the importance of careful surgical staging and of long-term follow-up in cases of primitive germ cell tumors of the ovary. (C) 1999 Academic Press. C1 Univ Mainz, Dept Pathol, D-55101 Mainz, Germany. Univ Mainz, Dept Obstet & Gynecol, D-55101 Mainz, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Kommoss, F (reprint author), Univ Mainz, Dept Pathol, D-55101 Mainz, Germany. RI Schmidt, Marcus/H-3383-2013 OI Schmidt, Marcus/0000-0003-1365-2414 NR 13 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 1999 VL 72 IS 3 BP 421 EP 424 DI 10.1006/gyno.1998.5256 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 174CE UT WOS:000079015900024 PM 10053117 ER PT J AU Mischoulon, D Fava, M Rosenbaum, JF AF Mischoulon, D Fava, M Rosenbaum, JF TI Strategies for augmentation of SSRI treatment: A survey of an academic psychopharmacology practice SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID SEROTONIN-REUPTAKE INHIBITORS; OBSESSIVE-COMPULSIVE DISORDER; ONE ANTIDEPRESSANT FAILS; BUSPIRONE AUGMENTATION; RESISTANT DEPRESSION; RISPERIDONE AUGMENTATION; REFRACTORY DEPRESSION; AUTORECEPTOR BLOCKADE; PSYCHIATRISTS; THERAPY C1 Massachusetts Gen Hosp, Dept Psychiat, Outpatient Div, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Outpatient Div, WAC-812,15 Parkman St, Boston, MA 02114 USA. NR 29 TC 17 Z9 17 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 1999 VL 6 IS 6 BP 322 EP 326 PG 5 WC Psychiatry SC Psychiatry GA 175XG UT WOS:000079120800005 PM 10370439 ER PT J AU Yuan, A Clarke, B AF Yuan, A Clarke, B TI An information criterion for likelihood selection SO IEEE TRANSACTIONS ON INFORMATION THEORY LA English DT Article DE likelihood selection; mutual information; rate distortion AB For a given source distribution, we establish properties of the conditional density achieving the rate distortion function lower bound as the distortion parameter varies, In the limit as the distortion tolerated goes to zero, the conditional density achieving the rate distortion function lower bound becomes degenerate in the sense that the channel it defines becomes error-free. As the permitted distortion increases to its limit, the conditional density achieving the rate distortion function lower hound defines a channel which no longer depends on the source distribution. In addition to the data compression motivation, we establish two results-one asymptotic, one nonasymptotic-showing that the the conditional densities achieving the rate distortion function lower bound make relatively weak assumptions on the dependence between the source and its representation. This corresponds, in Bayes estimation, to choosing a likelihood which makes relatively weak assumptions on the data generating mechanism if the source is regarded as a prior. Taken together, these results suggest one can use the conditional density obtained from the rate distortion function in data analysis. That is, when it is impossible to identify a "true" parametric family on the basis of physical modeling, our results provide both data compression and channel coding justification for using the conditional density achieving the rate distortion function lower bound as a likelihood. C1 Massachusetts Gen Hosp, Dept Anesthesia, Stat Res Lab, Clin 3, Boston, MA 02114 USA. Univ British Columbia, Dept Stat, Vancouver, BC V6T 1Z2, Canada. RP Yuan, A (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Stat Res Lab, Clin 3, Boston, MA 02114 USA. NR 23 TC 11 Z9 11 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9448 J9 IEEE T INFORM THEORY JI IEEE Trans. Inf. Theory PD MAR PY 1999 VL 45 IS 2 BP 562 EP 571 DI 10.1109/18.749003 PG 10 WC Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 173GJ UT WOS:000078972500013 ER PT J AU Avitahl, N Winandy, S Friedrich, C Jones, B Ge, YM Georgopoulos, K AF Avitahl, N Winandy, S Friedrich, C Jones, B Ge, YM Georgopoulos, K TI Ikaros sets thresholds for T cell activation and regulates chromosome propagation SO IMMUNITY LA English DT Article ID RECEPTOR SIGNAL-TRANSDUCTION; DNA-REPLICATION; KINASE INHIBITOR; PROTEIN-KINASE; RAPAMYCIN; PATHWAYS; POTENT; SITES; GENE; INTERLEUKIN-2 AB T cell activation involves the sustained accumulation of T cell receptor (TCR) and IL-2 receptor (IL-2R) mediated signaling events that promote cell cycle entry and progression. The Ikaros family of nuclear factors regulate this process by providing thresholds overcome by receptor signaling. T cells with reduced levels of Ikaros activity require fewer TCR engagement events for activation, exhibit a greater proliferative response to IL-2, and are less sensitive to inhibitors of TCR and IL-2R signaling. Upon T cell activation, Ikaros proteins localize in a higher-order chromatin structure where they colocalize with components of the DNA replication machinery. Proliferating T cells with reduced Ikaros activity display chromosome abnormalities. We propose that participation of Ikaros in higher-order chromatin structures controls cell cycle transitions and restricts DNA replication. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM katia_georgopoulos@cbrc.mgh.harvard.ed FU NIAID NIH HHS [R01 AI38342-03] NR 46 TC 112 Z9 112 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1999 VL 10 IS 3 BP 333 EP 343 DI 10.1016/S1074-7613(00)80033-3 PG 11 WC Immunology SC Immunology GA 181RJ UT WOS:000079455700006 PM 10204489 ER PT J AU Kim, J Sif, S Jones, B Jackson, A Koipally, J Heller, E Winandy, S Viel, A Sawyer, A Ikeda, T Kingston, R Georgopoulos, K AF Kim, J Sif, S Jones, B Jackson, A Koipally, J Heller, E Winandy, S Viel, A Sawyer, A Ikeda, T Kingston, R Georgopoulos, K TI Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes SO IMMUNITY LA English DT Article ID MI-2 AUTOANTIGEN; NUCLEOSOMAL DNA; FINGER; GENE; MUTATION; FAMILY AB The Ikaros gene family encodes zinc finger DNA-binding proteins essential for lineage determination and control of proliferation in the lymphoid system. Here, we report that, in the nucleus of a T cell, a major fraction of Ikaros and Aiolos proteins associate with the DNA-dependent ATPase Mi-2 and histone deacetylases, in a 2 MD complex. This Ikaros-NURD complex is active in chromatin remodeling and histone deacetylation. Upon T cell activation, Ikaros recruits Mi-2/HDAC to regions of heterochromatin. These studies reveal that Ikaros proteins are capable of targeting chromatin remodeling and deacetylation complexes in vivo. We propose that the restructuring of chromatin is a key aspect of Ikaros function in lymphocyte differentiation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr Prot Core, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02125 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM georgopoulos@cbrc.mgh.harvard.edu FU NIAID NIH HHS [R01 AI38342-04]; PHS HHS [R01] NR 45 TC 396 Z9 406 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1999 VL 10 IS 3 BP 345 EP 355 DI 10.1016/S1074-7613(00)80034-5 PG 11 WC Immunology SC Immunology GA 181RJ UT WOS:000079455700007 PM 10204490 ER PT J AU Rosenberg, ES LaRosa, L Flynn, T Robbins, G Walker, BD AF Rosenberg, ES LaRosa, L Flynn, T Robbins, G Walker, BD TI Characterization of HIV-1-specific T-helper cells in acute and chronic infection SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Immunological Correlates of Protection from HIV Infection and Disease CY APR 17-20, 1998 CL ST ANNES COLL, OXFORD, ENGLAND HO ST ANNES COLL DE T-helper cells; HIV; p24 antigen; primary HIV infection; immune reconstitution; AIDS-HIV ID LOW VIRAL LOAD; IMMUNODEFICIENCY-VIRUS; HIV-1 INFECTION; RESPONSES; LYMPHOCYTES; TYPE-1; MACAQUES; DISEASE; VIREMIA; MICE AB HIV-1 infection is associated with progressive and relentless destruction of the immune system in the majority of infected persons, but some persons appear to be able to successfully contain the virus in the absence of antiviral therapy. Such cases suggest that the host immune response can successfully contain the virus, and provide the rationale for concerted efforts to understand the host immune response to the virus and to develop new strategies to combat the infection with immune based therapies. Historically, the greatest hole in the immune repertoire in HIV-1 infection has been the lack of strong virus-specific proliferative responses. However, new studies have identified a potent Th cell response in some infected persons, and have shown a statistically significant negative correlation between plasma viremia and virus-specific CD4 T-helper cells directed at the p24 protein. Moreover, early institution of potent antiviral therapy in the earliest stages of acute HIV-1 infection have led to persistent, strong HIV-1-specific T-helper cell responses, analogous to those seen in persons who are able to control viremia in the absence of antiviral therapy. We hypothesize that this is because potent antiviral therapy is able to protect virus-specific Th cells as they become activated, and thus these cells are not lost in the earliest stages of infection. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Fruit St, Boston, MA 02114 USA. EM bwalker@helix.mgh.harvard.edu RI Robbins, Gregory/F-7988-2011 FU NIAID NIH HHS [R01 AI28568, R01 AI40873, R01 AI30914] NR 23 TC 60 Z9 61 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD MAR PY 1999 VL 66 IS 1-3 BP 89 EP 93 DI 10.1016/S0165-2478(98)00165-5 PG 5 WC Immunology SC Immunology GA 178GU UT WOS:000079258500014 PM 10203039 ER PT J AU Rosman, AS Lieber, CS AF Rosman, AS Lieber, CS TI Improving the response to hepatitis B vaccine SO INFECTIONS IN MEDICINE LA English DT Article DE immunization; hepatitis B virus (HBV); vaccines; renal failure; liver disease ID FRENCH HEMODIALYSIS UNITS; PLACEBO-CONTROLLED TRIAL; SURFACE-ANTIGEN VACCINE; 2-YEAR FOLLOW-UP; DIALYSIS PATIENTS; IMMUNE-RESPONSE; PREDIALYSIS PATIENTS; RANDOMIZED TRIAL; VIRUS-VACCINE; MEDICAL STAFF AB Although vaccines against hepatitis B virus have been a major advance in eradicating liver disease caused by hepatitis B infection, certain populations fail to mount an adequate protective immune response after vaccination. These include patients with chronic renal failure and alcoholism. Nonresponsiveness in healthy patients has been associated with smoking, increased age, excessive body mass, and certain HLA types or haplotypes. Some ways to improve vaccine responsiveness include increasing the dose and frequency of hepatitis B vaccine, giving booster doses, administering the vaccine as an intradermal injection, and using immunostimulants concomitantly. C1 Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. RP Rosman, AS (reprint author), Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. NR 41 TC 10 Z9 10 U1 0 U2 1 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD MAR PY 1999 VL 16 IS 3 BP 205 EP 210 PG 6 WC Infectious Diseases SC Infectious Diseases GA 178GT UT WOS:000079258400012 ER PT J AU Finegold, SM AF Finegold, SM TI Recollections of an early anaerobist SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Article ID GEN-NOV; FLORA RP Finegold, SM (reprint author), W Los Angeles Vet Affairs Med Ctr, Infect Dis Sect 111F, Los Angeles, CA 90073 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAR-APR PY 1999 VL 8 IS 3 BP 147 EP 150 DI 10.1097/00019048-199903000-00011 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 169KH UT WOS:000078746600011 ER PT J AU Murtaza, A Kuchroo, VK Freeman, GJ AF Murtaza, A Kuchroo, VK Freeman, GJ TI Changes in the strength of co-stimulation through the B7/CD28 pathway alter functional T cell responses to altered peptide ligands SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE altered peptide ligands; B7-1; CD80; co-stimulation; experimental autoimmune encephalomyelitis; T(h)1; T(h)2 ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN PROTEOLIPID PROTEIN; AUTOIMMUNE-DISEASE; COSTIMULATORY MOLECULES; BASIC-PROTEIN; CLONAL ANERGY; LYMPHOCYTE-T; ANTIGEN; SECRETION; NAIVE AB T cells require a TCR and a co-stimulatory signal for activation. We have examined the effect of the strength of TCR and co-stimulatory signals on proliferation and production of cytokines by differentiated T cell clones. The TCR signal was varied using antigen dose and altered peptide ligands. The co-stimulatory signal was varied by using as antigen-presenting cells, Chinese hamster ovary cell transfectants that express different levels of the B7-1 molecule with similar levels of MHC class II. Our results show that the level of cc-stimulation has a profound effect on the response to an antigen, and that a strong co-stimulatory signal can convert a weak agonist into a full agonist and an agonist into a superagonist. Antigenicity is not absolute but a function of the strengths of the TCR and co-stimulatory signals. Increasing the strength of co-stimulation can lower antigen concentration required for maximal proliferative responses by T cell clones by 5 log. These results show that the level of expression of co-stimulatory molecules will profoundly regulate T cell clonal expansion and effector functions. C1 Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kuchroo, VK (reprint author), Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, 75 Francis St, Boston, MA 02115 USA. FU NIAID NIH HHS [P01AI39671]; NINDS NIH HHS [NS30843, NS35685] NR 33 TC 31 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 1999 VL 11 IS 3 BP 407 EP 416 DI 10.1093/intimm/11.3.407 PG 10 WC Immunology SC Immunology GA 179JG UT WOS:000079322700011 PM 10221652 ER PT J AU Iwata, S Yamaguchi, N Munakata, Y Ikushima, H Lee, JF Hosono, O Schlossman, SF Morimoto, C AF Iwata, S Yamaguchi, N Munakata, Y Ikushima, H Lee, JF Hosono, O Schlossman, SF Morimoto, C TI CD26/dipeptidyl peptidase IV differentially regulates the chemotaxis of T cells and monocytes toward RANTES: possible mechanism for the switch from innate to acquired immune response SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE beta-chemokine; CD26; dipeptidyl peptidase IV; RANTES; transendothelial migration ID CHEMOKINE RECEPTORS; ADENOSINE-DEAMINASE; ACTIVATION ANTIGEN; PERIPHERAL-BLOOD; LYMPHOCYTES-T; HUMAN CD26; HIV-1; MOLECULE; SURFACE; IDENTIFICATION AB CD26, a 110 kDa cell surface glycoprotein, exhibits dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) enzyme activity and plays an important role in T cell co-stimulation, In the present study, the function of CD26/DPFIV in transendothelial migration was examined using beta-chemokines as chemoattractants. When soluble recombinant CD26 (sCD26/DPPIV+) was added to the transendothelial chemotaxis system, chemotactic migration of T cells toward RANTES was significantly enhanced, Addition of sCD26 to 50 ng/ml of RANTES enhanced the migratory response by a factor of two compared to RANTES alone, whereas mutant soluble CD26 (mCD26), lacking the DPPIV enzyme activity, had no enhancing effect on RANTES-induced T cell migration, In the process of analyzing the mechanisms of the enhancement of T cell migration by sCD26, we showed that RANTES was cleaved by sCD26 under physiologic conditions at the precise site characteristic of its enzyme specificity, However, synthesized RANTES which lacks two N-terminal amino acids showed a chemotactic activity equivalent to full-length RANTES on T cells, Furthermore, addition of sCD26 showed enhancement of T cell migration induced by both forms of RANTES. In contrast to T cells, the truncated RANTES is inactive in chemotaxis of purified monocytes and supplement of sCD26 but not mCD26 reduced the migratory response of monocytes to RANTES, These results suggest that CD26/DFPIV differentially regulate the chemotactic response of T cells and monocytes to RANTES. C1 Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Mol, Boston, MA 02115 USA. Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Minato Ku, Tokyo 108, Japan. Univ Tokyo, Inst Med Sci, Ctr AIDS Res, Minato Ku, Tokyo 108, Japan. RP Morimoto, C (reprint author), Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RI Iwata, Satoshi/A-8819-2011 FU NIAID NIH HHS [AI29530, AI12069]; NIAMS NIH HHS [AR33713] NR 40 TC 80 Z9 81 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 1999 VL 11 IS 3 BP 417 EP 426 DI 10.1093/intimm/11.3.417 PG 10 WC Immunology SC Immunology GA 179JG UT WOS:000079322700012 PM 10221653 ER PT J AU Biller, BMK AF Biller, BMK TI Hyperprolactinemia SO INTERNATIONAL JOURNAL OF FERTILITY AND WOMENS MEDICINE LA English DT Article; Proceedings Paper CT 4th Annual Conference of the World-Foundation-for-Medical-Studies-in-Female-Health CY DEC, 1998 CL NEW YORK, NEW YORK SP World Fdn Med Studies Female Hlth, Bristol Myers Squibb Co, Princeton, Eli Lilly & Co, Indianapolis, Janssen Cilag, New Brunswick, Ortho McNeil Pharm, Raritan, Berlex Labs, Ethicon Inc, 1st Professional Bank, Forest Labs, Glaxo Wellcome, Knoll Pharmaceut, Merck & Co, Miss Pharmacal, Myriad Genet Labs, Ortho Derm, Parke Davis, Pfizer Inc, Pharmacia & Upjohn Co, Procter & Gamble, Solvay Pharmaceut Inc, USIF Maxwell Roland Lectureship, Wyeth Ayerst Labs DE prolactinoma; diagnosis; treatment; bromocriptine; cabergoline ID CABERGOLINE; PROLACTINOMAS; BROMOCRIPTINE; AMENORRHEA; PREGNANCY; HORMONE; WOMEN AB Prolactinomas are the most common pituitary tumors. Hyperprolactinemia is characterized by increased production of prolactin, often leading to reproductive dysfunction and galactorrhea. Prolactinomas may also cause male-factor infertility by producing hypogonadism. In addition, if large, they can produce neurologic symptoms by mass effect in the sellar area. The diagnostic evaluation first requires exclusion of other causes of hyperprolactinemia, such as pregnancy, primary hypothyroidism, numerous medications, and miscellaneous causes. The second step in the diagnostic evaluation is to perform a head scan, preferably an MRT. This is essential in order to exclude a "pseudoprolactinoma" which would require surgery. Following diagnostic evaluation, the next step is to determine whether a patient with hyperprolactinemia has an indication for therapy, such as a macroprolactinoma (tumor > 1 cm), hypogonadism (risk of osteoporosis), infertility, significant galactorrhea, acne, hirsutism, or headache. The treatment of choice for nearly all patients with hyperprolactinemic disorders is medical. In most cases, dopamine agonists (bromocriptine, pergolide, cabergoline) are extremely effective in lowering serum prolactin, restoring gonadal function, decreasing tumor size, and improving visual fields. The main limitation is side effects, particuarly nausea or orthostatic dizziness. The newest dopamine agonist, cabergoline, can be given just once or twice a week, is more effective in normalizing prolactin and restoring menses than bromocriptine, and is significantly better tolerated. However, it is not yet recommended as first-line therapy for patients seeking fertility, because adequate safety data in pregnancy are not available. For the infrequent patient unable to tolerate, or resistant to, medical therapy, neurosurgical transsphenoidal resection may be necessary, particularly if the patient has a large lesion jeopardizing the optic chiasm. Hyperprolactinemia is a rewarding disorder to manage because patients typically respond well to medication, with restoration of menses and fertility. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Biller, BMK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,BUL 457B, Boston, MA 02114 USA. NR 13 TC 22 Z9 24 U1 0 U2 0 PU MEDICAL SCIENCE PUBLISHING INT INC PI PORT WASHINGTON PA 405 MAIN ST, PORT WASHINGTON, NY 11050 USA SN 1069-3130 J9 INT J FERTIL WOMEN M JI Int. J. Fertil. Womens Med. PD MAR-APR PY 1999 VL 44 IS 2 BP 74 EP 77 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 194WM UT WOS:000080217800004 PM 10338264 ER PT J AU Tarazi, FI Baldessarini, RJ AF Tarazi, FI Baldessarini, RJ TI Brain dopamine D-4 receptors: basic and clinical status SO INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY LA English DT Review DE antipsychotics; D-4; development; dopamine; genetics; mRNA; receptors; schizophrenia ID DEFICIT HYPERACTIVITY DISORDER; ATYPICAL ANTIPSYCHOTIC-DRUGS; NUCLEUS-ACCUMBENS-SEPTI; POSTMORTEM HUMAN BRAIN; D4 RECEPTOR; RAT-BRAIN; MESSENGER-RNA; PARKINSONS-DISEASE; GENE POLYMORPHISMS; D-4-LIKE RECEPTORS AB Since their discovery in 1991, an extraordinary amount of information has accumulated about the neurobiology and pharmacology of D-4 receptors in the mammalian central nervous system, making it timely to review salient aspects of this rapidly evolving research story and its relevance to clinical neuroscience. Recent progress in the molecular, genetic, anatomical, and functional characterization of D-4 receptors in the animal and human brain is yielding insights into their neurochemical and physiological roles in brain function. The temporal patterns of postnatal D-4 receptor development appear to differ in specific regions of mammalian forebrain. Postmortem neuropathological and clinical genetic studies have generally been disappointing regarding possible relationships of D-4 receptors to the pathophysiology or treatment of schizophrenia, however, they suggest relationships to other neuropsychiatric conditions, including attention deficit hyperactivity disorder, mood disorders, and Parkinson's disease. Several selective agonists and antagonists for D-4 receptors have been developed. Some are employed as experimental D-4 probes. The potential of D-4-selective ligands as innovative treatments for neuropsychiatric disorders requires further investigation. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. NR 149 TC 31 Z9 31 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1461-1457 J9 INT J NEUROPSYCHOP JI Int. J. Neuropsychopharmacol. PD MAR PY 1999 VL 2 IS 1 BP 41 EP 58 DI 10.1017/S1461145799001352 PG 18 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 267JC UT WOS:000084354000007 PM 11281970 ER PT J AU Zietman, AL Zehr, EM Shipley, WU AF Zietman, AL Zehr, EM Shipley, WU TI The long-term effect on PSA values of incidental prostatic irradiation in patients with pelvic malignancies other than prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate; radiation; prostate-specific antigen ID EXTERNAL-BEAM RADIATION; ANTIGEN; THERAPY; RADIOTHERAPY; ADENOCARCINOMA; PREDICTOR AB Purpose: To determine the effect of external beam radiation therapy on serum prostate-specific antigen (PSA) production by the benign prostate. Methods and Materials: We studied a cohort of 24 men receiving treatment for cancer of the bladder or rectum, The radiation fields in all cases encompassed the prostate gland, and none of the patients were known to have prostate cancer. All patients had 2 or more PSA estimations obtained in the years following their radiation treatment. A second group of 46 patients who had undergone radical external beam radiation therapy for prostate cancer and who were clinically disease free 8-22 years later were also observed, with a median of 5.8 years of PSA observations. Results: Only 3 of the 24 patients in the first group showed a significant rise of > 0.2 ng/ml in their serum PSA levels, with a median of 3.3 years follow-up from the first PSA test. Seven of 24 showed progressive declines, and 14 of 24 showed steady levels. The median PSA for this group was less than or equal to 0.5 ng/ml, Only 6 of the 46 in the second group showed a PSA rise of > 0.2 ng/ml, Thirty-four had stable values, and 6 had further declines. Again, the median PSA for the entire group was I 0.5 ng/ml, Conclusion: Recovery of prostatic secretory function is an uncommon event after external beam radiation. The concern that this might significantly confound new definitions of biochemical failure after radical radiation for prostate cancer that are based on progressively rising PSA values thus appears to be unfounded, (C) 1999 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02116 USA. RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cox 3, Boston, MA 02116 USA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 1999 VL 43 IS 4 BP 715 EP 718 DI 10.1016/S0360-3016(98)00484-2 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 177CY UT WOS:000079190900003 PM 10098425 ER PT J AU Encke, J Putlitz, JZ Wands, JR AF Encke, J Putlitz, JZ Wands, JR TI DNA vaccines SO INTERVIROLOGY LA English DT Article DE genetic immunization; hepatitis B virus; hepatitis C virus ID HEPATITIS-C VIRUS; B SURFACE-ANTIGEN; CYTOTOXIC T-LYMPHOCYTE; HUMORAL IMMUNE-RESPONSES; DIRECT GENE-TRANSFER; CYTOKINE-EXPRESSING PLASMIDS; MEDIATED IMMUNIZATION; VIRAL-HEPATITIS; CORE PROTEIN; STRUCTURAL PROTEINS AB Chronic infections with hepatitis B (HBV) and hepatitis C (HCV) virus are worldwide problems often leading to the development of chronic liver disease and hepatocellular carcinoma. Genetic immunizations with DNA encoding for structural and nonstructural proteins of HCV and HBV in experimental mice generate a broad base CD4+ and CD8+ cellular immune response which may be required for viral clearance from the host. DNA based immunization is a promising antiviral approach for the development of therapeutic and prophylactic vaccine against HBV and HCV. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Mol Hepatol Lab, Boston, MA USA. Univ Heidelberg, Med Klin 4, Heidelberg, Germany. Univ Freiburg, Med Klin 2, Freiburg, Germany. Brown Univ, Sch Med, Liver Res Ctr, Providence, RI 02912 USA. RP Wands, JR (reprint author), Brown Univ, Rhode Isl Hosp, Liver Res Ctr, 55 Claverick St, Providence, RI 02903 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 78 TC 29 Z9 39 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD MAR-JUN PY 1999 VL 42 IS 2-3 BP 117 EP 124 DI 10.1159/000024971 PG 8 WC Virology SC Virology GA 238RG UT WOS:000082723600006 PM 10516466 ER PT J AU Hampl, M Hampl, JA Schwarz, P Frank, S Hahn, M Schackert, G Saeger, HD Schackert, HK AF Hampl, M Hampl, JA Schwarz, P Frank, S Hahn, M Schackert, G Saeger, HD Schackert, HK TI Accumulation of genetic alterations in brain metastases of sporadic breast carcinomas is associated with reduced survival after metastasis SO INVASION & METASTASIS LA English DT Article DE sporadic breast carcinomas; distant metastases; breast cancer-related gene loci; combined LOH; postmetastatic survival ID TUMOR-SUPPRESSOR GENE; CANCER-SUSCEPTIBILITY GENES; MICROSATELLITE INSTABILITY; ALLELE LOSS; CELL CARCINOMA; POOR-PROGNOSIS; P53 MUTATIONS; CHROMOSOME 18Q; E-CADHERIN; HETEROZYGOSITY AB Tumor progression is characterized by stepwise accumulation of genetic alterations. To identify alterations associated with breast cancer metastasis, an analysis of comparative loss of heterozygosity (LOH) was performed on 38 primary sporadic breast carcinomas and 16 distant metastases. Two loci at 5q21 and 18q21 were chosen because of their reported increased deletion frequency in metastatic tumors. LOH at 17q21, 13q12-13, 17p13.1 and 11q22-23 was analyzed to determine whether there is a specific involvement of these breast cancer-associated gene loci in the metastatic process. Our data show that distant metastases are characterized by markedly increased LOH frequency at all loci examined. In both gene locus groups, significantly more distant metastases are affected by combined LOH. Furthermore, a significantly reduced postmetastatic survival time has been observed in patients with brain metastases affected by synchronous allelic loss at the four breast cancer-associated gene loci. Our results suggest that cumulative LOH of breast cancer-related gene loci is associated with a more aggressive phenotype of metastatic breast tumors. C1 Tech Univ Dresden, Fac Med, Dept Gen Thorac & Vasc Surg, D-8027 Dresden, Germany. RP Hampl, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,M 457, Boston, MA 02115 USA. RI Schwarz, Peter/B-5127-2013 OI Schwarz, Peter/0000-0001-6317-7880 NR 61 TC 2 Z9 2 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-1789 J9 INVAS METAST JI Invasion Metastasis PD MAR-APR PY 1999 VL 18 IS 2 BP 81 EP 95 PG 15 WC Oncology SC Oncology GA 208PE UT WOS:000080999600003 ER PT J AU Lee, FY Mankin, HJ Fondren, G Gebhardt, MC Springfield, DS Rosenberg, AE Jennings, LC AF Lee, FY Mankin, HJ Fondren, G Gebhardt, MC Springfield, DS Rosenberg, AE Jennings, LC TI Chondrosarcoma of bone: An assessment of outcome SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID PROGNOSTIC FACTORS; DEDIFFERENTIATED CHONDROSARCOMA; SURGICAL-TREATMENT; CARTILAGE TUMORS; P53 EXPRESSION; DNA CONTENT; GRADE; ENCHONDROMA; SURGERY; PLOIDY AB Background: The data on 227 patients who had been managed for a chondrosarcoma at one institution were reviewed to determine the nature of the lesions, the predictors of outcome, and whether there were any ways to change the treatment approaches to improve the results. Methods: The patients were followed for a mean duration of six years (range, three to twenty-five years). The mean age of the patients was forty-seven Sears (range, nine to eighty-four years). The most prevalent sites of the tumors were the femur (seventy-eight), the pelvis (fifty-one), and the humerus (thirty-nine). The tumors were divided into two groups according to histological grade. Eighty-six tumors (sixteen atypical enchondromas and seventy grade-1 chondrosarcomas) that were locally destructive but were associated,vith a low likelihood of metastasis were considered to be low-grade. The remaining 141 lesions, which were locally destructive, potentially metastatic, and capable of causing death, were thought to be high-grade. One hundred and three of these 141 lesions were grade 2, and thirty-eight were grade 3 (eighteen of the thirty-eight were grade 3 only, and twenty were both grade 3 and dedifferentiated). Two hundred and twenty-four patients were managed with resection and a limb-sparing procedure; the remaining three patients had an amputation. Postoperative adjuvant radiation was used for fifty-six patients; chemotherapy, for thirty-five; and both radiation and chemotherapy, for nineteen. Flow cytometric patterns were analyzed for 105 patients. Results: The patients who had a high-grade tumor were older than those who had a low-grade tumor (mean age [and standard deviation], 50 +/- 17.0 years compared with 40 +/- 15.9 years; p < 0.001). Pathological fracture, metastasis, local recurrence, and death were more prevalent in the group that had a high-grade lesion (p < 0.001). Predictors of metastasis and death in that group of patients included local recurrence, a pelvic location of the tumor, a tumor that was more than 100 cubic centimeters in size, a ploidic abnormality (aneuploidy coupled with a high mean DNA index), a histological grade of 3, and a dedifferentiated type of tumor (p < 0.001). Conclusions: Although the data are suggestive, with the numbers available for study we could not detect a significant difference in the rates of pulmonary metastasis and death between the patients who had a grade-3 lesion and those who had a grade-3 lesion that was also dedifferentiated. However, the interval between diagnosis and death was 32 +/- 22.8 months for the patients who had a grade-3 lesion compared with 5 +/- 3.7 months for those who had a grade-3 lesion that was also dedifferentiated (p < 0.001). Overall, patients who had had a resection with wide margins (margins extending outside the reactive zone) had a longer duration of survival than did those who had had a so-called marginal resection (margins extending outside the tumor but within the reactive zone) or an intralesional resection (margins,within the lesion) (p < 0.04). Adjunctive chemotherapy or radiation, or both (which, it must be noted, was used, without a protocol, in a relatively small number of patients), after an intralesional resection, for recurrent disease, or for distant metastasis did not appear to alter the outcome. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Lee, FY (reprint author), Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. NR 42 TC 186 Z9 199 U1 0 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 1999 VL 81A IS 3 BP 326 EP 338 PG 13 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 179FN UT WOS:000079315300004 PM 10199270 ER PT J AU Anderson, MJ Harris, WH AF Anderson, MJ Harris, WH TI Total hip arthroplasty with insertion of the acetabular component without cement in hips with total congenital dislocation or marked congenital dysplasia SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID REPLACEMENT AB Background: End-stage osteoarthritis secondary to total congenital dislocation or severe congenital dysplasia of the hip (class B or C according to the system of Eftekhar or type 2 or 3 according to the system of Hartofilakidis et al,) in adults presents special problems with regard to reconstruction of the hip. The purpose of the present study was to assess the intermediate-term results associated with the use of a porous ingrowth acetabular component for the treatment of these difficult cases. Methods: We performed a prospective study of a consecutive series of twenty-one patients (twenty-four hips) who had had a primary total hip arthroplasty with use of a hemispherical acetabular component that was inserted without cement and fixed with screws. No patient was lost to follow-up. Three patients (four hips) died, of causes unrelated to the total hip arthroplasty, before a minimum duration of follow-up of five years. None of these patients had had revision. Of the remaining eighteen patients (twenty hips), fifteen were women and three were men, Ten hips had total dislocation, and ten had severe dysplasia, Results: After an average duration of follow-up of eighty-three months (range, sixty-four to 102 months), the average Harris hip score was 90 points (range, 68 to 97 points), No patient had revision, loosening, or migration of the acetabular component; pelvic osteolysis; or a continuous radiolucent line at the mesh-bone interface of the acetabular component. The average rate of polyethylene wear was 0.08 millimeter per year (range, zero to 0.21 millimeter per year). Conclusions: The porous ingrowth acetabular component that was used in the present study functioned well at the time of the intermediate-term follow-up of this group of patients who had marked congenital dysplasia or total dislocation of the hip. The use of this component decreased the need for structural acetabular grafts. This component appears to perform as well as larger components of this design that have been assessed after similar durations of follow-up. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Adult Reconstruct Serv, Boston, MA 02114 USA. RP Anderson, MJ (reprint author), Blount Orthopaed Clin, 625 E St Paul Ave, Milwaukee, WI 53202 USA. NR 26 TC 60 Z9 77 U1 0 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 1999 VL 81A IS 3 BP 347 EP 354 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 179FN UT WOS:000079315300006 PM 10199272 ER PT J AU Perlmutter, GS Leffert, RD AF Perlmutter, GS Leffert, RD TI Results of transfer of the pectoralis major tendon to treat paralysis of the serratus anterior muscle SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background: Paralysis of the serratus anterior muscle can be functionally disabling. As a result of the scapular winging associated,vith such paralysis, the scapula does not remain apposed to the thorax when the upper extremity is elevated forward at the shoulder. This produces functional disability associated with pain and loss of a stable base for movement of the upper extremity Methods: We reviewed the results of transfer of the pectoralis major tendon with the addition of a fascial graft in sixteen patients who had paralysis of the serratus anterior. The average age of the patients at the time of the operation was thirty-three years (range, twenty to fifty-five years). Electrodiagnostic studies confirmed the presence of an isolated injury of the long thoracic nerve, The index operation was performed sixteen months to eleven years after the onset of pain and weakness. The etiology of the paralysis was idiopathic in two patients, traumatic in seven, and secondary to operative intervention in seven. All patients had pain in the shoulder on the side of the paralysis. Results: The result was excellent for eight patients, good for five, and fair for one at an average of four years and three months (range, two years and one month to nine years) postoperatively, There were two failures, both of which occurred after a traumatic event. Of the fourteen patients in whom the procedure did not fail, eight were asymptomatic and had normal function, five had intermittent mild discomfort, and one had frequent mild pain without any winging of the scapula, The average Constant and Murley score for the fourteen patients in whom the procedure did not fail increased from 36 points preoperatively to 92 points postoperatively, Conclusions: The index procedure successfully alleviated the functional disability caused by paralysis of the serratus anterior muscle. C1 Massachusetts Gen Hosp, Orthopaed Surg Serv, Boston, MA 02114 USA. RP Perlmutter, GS (reprint author), Massachusetts Gen Hosp, Orthopaed Surg Serv, Profess Off Bldg,275 Cambridge St,Suite 403, Boston, MA 02114 USA. EM gperlmutter@partners.org NR 26 TC 27 Z9 28 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 1999 VL 81A IS 3 BP 377 EP 384 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 179FN UT WOS:000079315300010 PM 10199276 ER PT J AU Lerner, J Safren, SA Henin, A Warman, M Heimberg, RG Kendall, PC AF Lerner, J Safren, SA Henin, A Warman, M Heimberg, RG Kendall, PC TI Differentiating anxious and depressive self-statements in youth: Factor structure of the Negative Effect Self-Statement Questionnaire among youth referred to an anxiety disorders clinic SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Association-for-Advancement-of-Behavior-Therapy CY NOV, 1997 CL MIAMI BEACH, FLORIDA SP Assoc Adv Behav Therapy ID CONTENT-SPECIFICITY HYPOTHESIS; COGNITIVE CONTENT-SPECIFICITY; TRIPARTITE MODEL; SOCIAL ANXIETY; CHILDREN; ADOLESCENTS; AFFECTIVITY; INTERVIEW; COMORBIDITY; VALIDATION AB Conducted a factor analysis on the items from the Negative Affect Self-Statement Questionnaire (NASSQ; Ronan, Kendall, & Rowe, 1994). This analysis yielded 4 factors (Depressive Self-Statements, Anxiety/Somatic Self-Statements, Negative Affect Self-Statements, and positive Affect Self-Statements) broadly consistent with both the content-specificity hypothesis (Beck & Clark, 1988) and L. A. Clark and Watson's (1991b) tripartite model of anxiety and depression, The association between children's self-talk and measures of trait anxiety and depression was also examined. Self-statements with content theoretically specific to depression were the best predictors of self-reported depressive symptoms, but the results were less clear for trait anxiety. Overall, these results provide evidence for the discriminability of anxious and depressive self-talk in youth and for the utility of the NASSQ as a cognitive assessment instrument. C1 Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Heimberg, RG (reprint author), Temple Univ, Dept Psychol, 1701 N 13th St,Weiss Hall, Philadelphia, PA 19122 USA. EM rheimber@nimbus.ocis.temple.edu FU PHS HHS [44119, 44042] NR 63 TC 24 Z9 24 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0047-228X J9 J CLIN CHILD PSYCHOL JI J. Clin. Child Psychol. PD MAR PY 1999 VL 28 IS 1 BP 82 EP 93 DI 10.1207/s15374424jccp2801_7 PG 12 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 168MW UT WOS:000078697700007 PM 10070609 ER PT J AU Hayes, FJ McNicholl, DJ Schoenfeld, D Marsh, EE Hall, JE AF Hayes, FJ McNicholl, DJ Schoenfeld, D Marsh, EE Hall, JE TI Free alpha-subunit is superior to luteinizing hormone as a marker of gonadotropin-releasing hormone despite desensitization at fast pulse frequencies SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; GNRH-DEFICIENT MEN; FOLLICLE-STIMULATING-HORMONE; HYPOTHALAMIC-PITUITARY AXIS; PEAK-DETECTION ALGORITHMS; POSTMENOPAUSAL WOMEN; RAT PITUITARY; DECONVOLUTION ANALYSIS; CONTEMPORARY-ASPECTS; PULSATILE SECRETION AB A pulsatile pattern of GnRH stimulation is essential for normal secretion of luteinizing hormone (LH), while both continuous and fast-frequency GnRH stimulation result in a paradoxical decrease in gonadotrope responsiveness known as desensitization. Under physiological conditions there is striking concordance between the pulsatile secretion of LH and the glycoprotein free alpha-subunit (FAS). The aims of this study were to determine whether the FAS response to GnRH is also decreased at fast frequencies of GnRH stimulation and whether FAS is superior to LH as a marker of GnRH secretory activity at fast-pulse frequencies. The model of GnRH-deficient men was chosen to permit precise control of the dose and frequency of GnRH stimulation of the gonadotrope. The frequency of iv administration of GnRH to 5 GnRH-deficient men was progressively increased from every 120 to every 60 min, from 60 to 30 min, and from 30 to 15 min during three 12-h admissions, 1 week apart. The bolus dose of GnRH remained constant and was set at that dose previously shown to produce physiological concentrations and amplitudes of LH secretion and normal testosterone levels. As the frequency of GnRH stimulation was increased, a progressive rise in mean FAS levels was noted (353 +/- 13, 448 +/- 42, 466 +/- 50, and 698 +/- 85 ng/L [mean +/- SEM] for 120, 60, 30, and 15 min intervals; P < 0.005). However, normalization of mean FAS levels to account for the increase in total GnRH delivered with increasing frequencies revealed a progressive decrease in pituitary responsiveness to each GnRH bolus with increasing frequency of stimulation (353 +/- 13, 224 +/- 21, 117 +/- 13, 87 +/- 11 ng/L; P < 0.001). The decrease in normalized mean levels was supported by a decrease in the FAS pulse amplitude with increasing frequency (517 +/- 53, 365 +/- 50, 176 +/- 29 ng/L for 120, 60, and 30 min intervals, respectively; P < 0.005). At interpulse intervals of 120 and 60 min, there was complete concordance of LH and FAS pulses in response to GnRH. However, at the 30-min frequency FAS proved to be a better marker of GnRH with a higher true positive rate and lower number of false positives than LH (P < 0.05). At all frequencies, the number of false positive pulses detected tended to be lower for FAS than for LH (P = 0.06). From these data we conclude that FAS is subject to desensitization in response to increasing frequencies of GnRH administration in GnRH-deficient men, but is superior to LH as a surrogate marker of GnRH pulse generator activity at fast pulse frequencies. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Dept Biostat, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 5,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01 RR01066]; NIA NIH HHS [R01 AG13241, R01 AG013241]; NICHD NIH HHS [P30 HD28138] NR 75 TC 60 Z9 60 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 MAR PY 1999 VL 84 IS 3 BP 1028 EP 1036 DI 10.1210/jc.84.3.1028 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176JC UT WOS:000079147100036 PM 10084591 ER PT J AU Viola, JPB Rao, A AF Viola, JPB Rao, A TI Molecular regulation of cytokine gene expression during the immune response SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Review DE cytokine genes; immune response; molecular regulation ID TRANSCRIPTION FACTOR NFAT1; TISSUE-SPECIFIC EXPRESSION; CELL RECEPTOR-ALPHA; HELPER TYPE-1 CELLS; DNA-BINDING PROTEIN; MURINE IL-4 GENE; HUMAN T-CELLS; TARGETED DISRUPTION; TH2 CELLS; NF-ATC AB Cytokine expression by immune system cells plays an important role in the regulation of the immune response. On first encounter with antigen, naive CD4(+) T helper (Th) cells differentiate into cytokine-producing effector cells. Two types of effector cells characterized by their distinct expression of cytokine profiles have been described. Th1 cells produce IL-2 and IFN-gamma, whereas Th2 cells produce IL-4, 11.-5, IL-6, IL-10, and IL-13. In many pathological situations, the balance between Th 1 and Th? immune responses determines the outcome of diverse immunologically mediated clinical syndromes including infectious, autoimmune, and allergic diseases. However, the molecular basis for the tissue-specific expression of Th1/Th2-like cytokines has remained elusive. In this rt view we evaluate the possible in vivo role of different transcription factors and transcriptional mechanisms in T cell differentiation and the immune response. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Inst Nacl Canc Canc, Programa Med Expt, Ctr Pesquisa Basica, Rio De Janeiro, Brazil. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Alpert Bldg 152,200 Longwood Ave, Boston, MA 02215 USA. NR 129 TC 38 Z9 40 U1 1 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAR PY 1999 VL 19 IS 2 BP 98 EP 108 DI 10.1023/A:1020502516196 PG 11 WC Immunology SC Immunology GA 187HB UT WOS:000079780200002 PM 10226884 ER PT J AU Stagg, AR Fleming, SC Baker, MA Sakamoto, M Cohen, N Neufeld, EJ AF Stagg, AR Fleming, SC Baker, MA Sakamoto, M Cohen, N Neufeld, EJ TI Defective high-affinity thiamine transporter leads to cell death in thiamine-responsive megaloblastic anemia syndrome fibroblasts SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SACCHAROMYCES-CEREVISIAE; DEFICIENCY; GENE AB We have investigated the cellular pathology of the syndrome called thiamine-responsive megaloblastic anemia (TRMA) with diabetes and deafness. Cultured diploid fibroblasts were grown in thiamine-free medium and dialyzed serum. Normal fibroblasts survived indefinitely without supplemental thiamine, whereas patient cells died in 5-14 days (mean 3.5 days), and heterozygous cells survived for more than 30 days. TRMA fibroblasts were rescued from death with 10-30 nM thiamine (in the range of normal plasma thiamine concentrations). Positive terminal deoxynucleotide transferase-mediated dUTP nick end-labeling (TUNEL) staining suggested that cell death was due to apoptosis. We assessed cellular uptake of [H-3]thiamine at submicromolar concentrations. Normal fibroblasts exhibited saturable, high-affinity thiamine uptake (K-m 400-550 nM; V-max 11 pmol/min/10(6) cells) in addition to a low-affinity unsaturable component. Mutant cells lacked detectable high-affinity uptake. At 30 nM thiamine, the rate of uptake of thiamine by TRMA fibroblasts was 10-fold less than that of wild-type, and cells from obligate heterozygotes had an intermediate phenotype. Transfection of TRMA fibroblasts with the yeast thiamine transporter gene THI10 prevented cell death when cells were grown in the absence of supplemental thiamine. We therefore propose that the primary abnormality in TRMA is absence of a high-affinity thiamine transporter and that low intracellular thiamine concentrations in the mutant cells cause biochemical abnormalities that lead to apoptotic cell death. C1 Childrens Hosp, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Lab Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Technion Israel Inst Technol, Tamkin Mol Genet Facil, IL-31096 Haifa, Israel. RP Neufeld, EJ (reprint author), Div Hematol, Enders 720,300 Longwood Ave, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011 FU NHLBI NIH HHS [HL-07574, HL-49196, T32 HL007574] NR 21 TC 50 Z9 50 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1999 VL 103 IS 5 BP 723 EP 729 DI 10.1172/JCI3895 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 173CF UT WOS:000078963100018 PM 10074490 ER PT J AU Gosling, J Slaymaker, S Gu, L Tseng, S Zlot, CH Young, SG Rollins, BJ Charo, IF AF Gosling, J Slaymaker, S Gu, L Tseng, S Zlot, CH Young, SG Rollins, BJ Charo, IF TI MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SMOOTH-MUSCLE CELLS; TRANSGENIC MICE; MONOCLONAL-ANTIBODY; A-I; LESIONS; HYPERCHOLESTEROLEMIA; EXPRESSION; ATHEROGENESIS AB The earliest recognizable atherosclerotic lesions are fatty streaks composed of lipid-laden macrophages (foam cells). Circulating monocytes are the precursors of these foam cells, but the molecular mechanisms that govern macrophage trafficking through the vessel wall are poorly understood. Monocyte chemoattractant protein-1 (MCP-1), a member of the chemokine (chemotactic cytokine) family, is a potent monocyte agonist that is upregulated by oxidized lipids. Recent studies in hypercholesterolemic mice lacking apo E or the low-density lipoprotein receptor have suggested a role for MCP-1 in monocyte recruitment to early atherosclerotic lesions. To determine if MCP-1 is critically involved in atherogenesis in the setting of elevated physiological plasma cholesterol levels, we deleted the MCP-1 gene in transgenic mice expressing human apo B. Here we report that the absence of MCP-1 provides dramatic protection from macrophage recruitment and atherosclerotic lesion formation in apo B transgenic mice, without altering lipoprotein metabolism. Taken together with the results of earlier studies, these data provide compelling evidence that MCP-1 plays a critical role in the initiation of atherosclerosis. C1 Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Charo, IF (reprint author), Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, POB 419100, San Francisco, CA 94141 USA. FU NHLBI NIH HHS [HL-41633, HL-52773, P01 HL041633, R01 HL052773] NR 46 TC 468 Z9 499 U1 1 U2 14 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 1999 VL 103 IS 6 BP 773 EP 778 DI 10.1172/JCI5624 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 177GW UT WOS:000079203100003 PM 10079097 ER PT J AU Sutton, DA Timm, WD Morgan-Jones, G Rinaldi, MG AF Sutton, DA Timm, WD Morgan-Jones, G Rinaldi, MG TI Human phaeohyphomycotic osteomyelitis caused by the coelomycete Phomopsis saccardo 1905: Criteria for identification, case history, and therapy SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID PLEUROPHOMOPSIS-LIGNICOLA; PHOMA AB The Sphaeropsidales, coelomycetous fungi producing asexual conidia within enclosed conidiomata (pycnidia), are saprobic on numerous vascular plants. Despite their ubiquitous nature, only a limited number of genera have been documented as causing human disease. We report what we believe to be the first human case of osteomyelitis due to a Phomopsis species in a chronically immunosuppressed female. The patient developed a subcutaneous abscess on the distal phalanx of the right fourth finger complicated by osteomyelitis. Operative specimens revealed fungal hyphae and a pure culture of mould. The patient was treated with a 6-month course of itraconazole. At 16 months of follow-up, she remained free of recurrence. Phomopsis species differ from the similar, more frequently reported Phoma species by having immersed, thick walled, multiloculate conidiomata and by the production of alpha (short, ellipsoidal) and beta (long, filamentous) conidia. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. Infect Dis Specialists SE Wisconsin SC, Milwaukee, WI 53210 USA. Auburn Univ, Auburn, AL 36849 USA. RP Sutton, DA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 23 TC 21 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 1999 VL 37 IS 3 BP 807 EP 811 PG 5 WC Microbiology SC Microbiology GA 166MC UT WOS:000078579500063 PM 9986861 ER PT J AU Diehl, V Sextro, M Franklin, J Hansmann, ML Harris, N Jaffe, E Poppema, S Harris, M Franssila, K van Krieken, J Marafioti, T Anagnostopoulos, I Stein, H AF Diehl, V Sextro, M Franklin, J Hansmann, ML Harris, N Jaffe, E Poppema, S Harris, M Franssila, K van Krieken, J Marafioti, T Anagnostopoulos, I Stein, H TI Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: Report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LARGE-CELL LYMPHOMA; FOLLICULAR LYMPHOMA; REED-STERNBERG; THERAPY; PATTERN; CHAIN AB Purpose: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from or her forms of Hodgkin's disease, including classical Hodgkin's disease (CHD), However, large-scale clinical studies were tacking, This multicenter, retrospective study investigated the clinical characteristics and course of LPHD patients and lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according to morphologic and immunophenotypic criteria, Materials and Methods: Clinical data and biopsy material of all available cases initially submitted as LPHD were collected from 17 European and American centers, stained, and reclassified by expert pathologists. Results: The 426 assessable cases were reclassified as LPHD (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were predominantly male, with early-stage disease and few risk factors. Patients with LRCHD were significantly older, Survival and failure-free survival rates with adequate therapy were similar for patients with LPHD and LRCHD, and were stage-dependent and not significantly better than stage-comparable results for CHD (German trial data), Twenty seven percent of relapsing LPHD patients had multiple relapses, which is significantly more than the 5% of relapsing LRCHD patients who had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients herd significantly superior survival after relapse compared with LRCHD or CHD patients; however, this was partly due to the younger average age of LPHD patients, Conclusion: The two subgroups of LPHD and LRCHD bore a close clinical resemblance that was distinct from CHD; the course was similar to that of comparable nodular sclerosis and mixed cellularity patients, Thorough staging is necessary to detect advanced disease in LPHD and LRCHD patients. The question of how to treat such patients, either by reducing treatment intensity or following a "watch and wait" approach, remains unanswered, (C) 1999 by American Society of Clinical Oncology. C1 Univ Cologne, Dept Internal Med, Cologne, Germany. Univ Frankfurt, Dept Pathol, D-6000 Frankfurt, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. Univ Groningen, Groningen, Netherlands. Christie Hosp Manchester, Manchester, Lancs, England. Univ Helsinki, Cent Hosp, Helsinki, Finland. Akad Ziekenhuis, Leiden, Netherlands. Free Univ Berlin, Klinikum Benjamin Franklin, D-12200 Berlin, Germany. RP Diehl, V (reprint author), Innere Med Klin 1, D-50924 Cologne, Germany. RI Marafioti, Teresa/B-4493-2009; Poppema, Sibrand/D-1204-2012; van Krieken, Joannes/D-4138-2009 OI van Krieken, Joannes/0000-0001-6544-1040 NR 35 TC 189 Z9 201 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1999 VL 17 IS 3 BP 776 EP 783 PG 8 WC Oncology SC Oncology GA 173GM UT WOS:000078972800007 PM 10071266 ER PT J AU Theriault, RL Lipton, A Hortobagyi, GN Leff, R Gluck, S Stewart, JF Costello, S Kennedy, I Simeone, J Seaman, JJ Knight, RD Mellars, K Heffernan, M Reitsma, DJ AF Theriault, RL Lipton, A Hortobagyi, GN Leff, R Gluck, S Stewart, JF Costello, S Kennedy, I Simeone, J Seaman, JJ Knight, RD Mellars, K Heffernan, M Reitsma, DJ CA Protocol 18 Aredia Breast Canc Study Grp TI Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: A randomized, placebo-controlled trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTASES; INHIBITION; CARCINOMA; APD; RESORPTION; EFFICACY; MYELOMA AB Purpose: To assess whether pamidronate can reduce the frequency of skeletal morbidity in women with lytic bone metastases from breast cancer treated with hormone therapy. Patients and Methods: Three hundred seventy-two women with breast cancer who had at least one lytic bone lesion and who were receiving hormonal therapy were randomized to receive 90 mg of pamidronate or placebo as a 2-hour intravenous infusion given in double-blind fashion every 4 weeks for 24 cycles. patients were evaluated for skeletal complications: pathologic fractures, spinal cord compression, irradiation of or surgery on bone, or hypercalcemia. The skeletal morbidity rate (the ratio of the number of skeletal complications to the rime an trial) was the primary efficacy variable. Bone pain, use of analgesics, quality of life, performance status, bone tumor response, and biochemical parameters were also evaluated, Results: One hundred eighty-two patients who received pamidronate and 189 who received placebo were assessable. The skeletal morbidity rate was significantly reduced at 12, 18, and 24 cycles in patients treated with 90 mg of pamidronate (P = .028, .023, and .008, respectively). At 24 cycles, the proportion of patients having had any skeletal complication was 56% in the pamidronate group and 67% in the placebo group (P = .027), The time to the first skeletal complication was longer for patients receiving pamidronate than for those given placebo (P = .049), there was no statistical difference in survival or in objective bone response rate. Pamidronate was well tolerated, Conclusion: Treatment with 90 mg of pamidronate as a 2-hour intravenous infusion every 4 weeks in addition to hormonal therapy significantly reduces skeletal morbidity from osteolytic metastases. (C) 1999 by American Society of Clinical Oncology. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. Milton S Hershey Med Ctr, Hershey, PA USA. Georgia Canc Specialists, Decatur, GA USA. NE Ontario Reg Ctr, Sudbury, ON, Canada. Newcastle Mater Misericordiae Hosp, Waratah, NSW, Australia. Dunedin Publ Hosp, Dunedin, New Zealand. Waikato Hosp, Hamilton, New Zealand. Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharmaceut, E Hanover, NJ USA. RP Theriault, RL (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Breast Med Oncol, 1515 Holcombe Blvd,Box 56, Houston, TX 77030 USA. EM rtheriau@mdanderson.org NR 31 TC 400 Z9 411 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1999 VL 17 IS 3 BP 846 EP 854 PG 9 WC Oncology SC Oncology GA 173GM UT WOS:000078972800016 PM 10071275 ER PT J AU Bluman, LG Rimer, BK Berry, DA Borstelmann, N Iglehart, JD Regan, K Schildkraut, J Winer, EP AF Bluman, LG Rimer, BK Berry, DA Borstelmann, N Iglehart, JD Regan, K Schildkraut, J Winer, EP TI Attitudes, knowledge, and risk perceptions of women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FAMILY HISTORY; HEREDITARY BREAST; DECISION-MAKING; GENE BRCA1; SUSCEPTIBILITY; IMPACT; TRIAL AB Purpose: This study examined baseline knowledge, beliefs, and risk perceptions among a group of 200 women with breast and/or ovarian cancer who participated in a trial designed to improve decision making about genetic testing for BRCA1 and BRCA2. Patients and Methods: Women were identified by self-referral, physician referral, and tumor registry extraction and invited to participate in a randomized trial in which testing for BRCA I and BRCA2 was offered free of charge, Subjects completed baseline questionnaires and interviews that assessed knowledge, attitudes, and perceptions of risk of having an alteration in BRCA1 or BRCA2. Results: Sixty percent of women overestimated their chances of having a BRCA1 or BRCA2 mutation compared with estimates from a BRCA 1/BRCA2 risk model. Women who have at least three relatives with breast or ovarian cancer were one third (95% confidence interval, 0.2 to 0.6) as likely to overestimate their risk of having a BRCA1 or BRCA2 mutation compared with women who have two or fewer affected relatives. Knowledge wets limited about BRCA1 and BRCA2 mutations and cancer risk associated with gene mutations, Eighty-four percent of the women indicated a probable or definite interest in testing. Conclusion: A high proportion of the high-risk women in this study had knowledge deficits about BRCA1 and BRCA2 and overestimated their risk of having a mutation, Although some degree of caution should be used in generalizing the results of this study to practice settings, the data provide insight into the challenges clinicians will face in communicating with patients about cancer genetics. (C) 1999 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Breast Oncol Ctr, Dept Care Coordinat, Boston, MA 02115 USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27706 USA. Duke Univ, Inst Stat & Decis Sci, Durham, NC 27706 USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Bluman, LG (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, Dept Care Coordinat, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 68438] NR 43 TC 91 Z9 91 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1999 VL 17 IS 3 BP 1040 EP 1046 PG 7 WC Oncology SC Oncology GA 173GM UT WOS:000078972800040 PM 10071299 ER PT J AU Crismon, ML Trivedi, M Pigott, TA Rush, AJ Hirschfeld, RMA Kahn, DA DeBattista, C Nelson, JC Nierenberg, AA Sackeim, HA Thase, ME AF Crismon, ML Trivedi, M Pigott, TA Rush, AJ Hirschfeld, RMA Kahn, DA DeBattista, C Nelson, JC Nierenberg, AA Sackeim, HA Thase, ME CA Texas Consensus Panel Med Treatment Major Depre TI The Texas Medication Algorithm Project: Report of the Texas Consensus Conference Panel on medication treatment of major depressive disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ANTIDEPRESSANT; GUIDELINES; FLUOXETINE AB Background: This article describes the development of consensus medication algorithms for the treatment of patients with major depressive disorder in the Texas public mental health system. To the best of our knowledge, the Texas Medication Algorithm Project (TMAP) is the first attempt to develop and prospectively evaluate consensus-based medication algorithms for the treatment of individuals with severe and persistent mental illnesses. The goals of the algorithm project are to increase the consistency of appropriate treatment of major depressive disorder and to improve clinical outcomes of patients with the disorder. Method: A consensus conference composed of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families was convened to develop evidence-based consensus algorithms for the pharmacotherapy of major depressive disorder in the Texas mental health system. After a series of presentations and panel discussions, the consensus panel met and drafted the algorithms, Results: The panel consensually agreed on algorithms developed for bath nonpsychotic and psychotic depression. The algorithms consist of systematic strategies to define appropriate treatment interventions and tactics to assure optimal implementation of the strategies, Subsequent to the consensus process, the algorithms were further modified and expanded iteratively to facilitate implementation on a local basis. Conclusion: These algorithms serve as the initial foundation for the development and implementation of medication treatment algorithms for patients treated in public mental health systems. Specific issues related to adaptation, implementation, feasibility testing, and evaluation of outcomes with the pharmacotherapeutic algorithms will be described in future articles. C1 Univ Texas, Coll Pharm, Austin, TX 78712 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Texas, Med Branch, Dept Psychiat, Galveston, TX 77550 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Lubbock Reg MHMR Ctr, Lubbock, TX USA. Texas Tech Hlth Sci Ctr, Dept Psychiat, Lubbock, TX USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Univ Texas, Coll Pharm, Austin, TX 78712 USA. Depress Man Depress Assoc Texas, Dallas, TX USA. Austin Travis Cty MHMR Ctr, Austin, TX USA. Tarrant Cty MHMR Serv, Ft Worth, TX USA. RP Crismon, ML (reprint author), Univ Texas, Coll Pharm, MC A1910, Austin, TX 78712 USA. OI Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [5 R24 MH53799-03] NR 28 TC 190 Z9 194 U1 0 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 1999 VL 60 IS 3 BP 142 EP 156 PG 19 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 180CR UT WOS:000079368100002 PM 10192589 ER PT J AU Lenderking, WR Tennen, H Nackley, JF Hale, MS Turner, RR Testa, MA AF Lenderking, WR Tennen, H Nackley, JF Hale, MS Turner, RR Testa, MA TI The effects of venlafaxine on social activity level in depressed outpatients SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSION; NEGATIVE AFFECT; PERSONALITY; EXPERIENCE; ADJUSTMENT; SYMPTOMS; EFFICACY; SCALE; LIFE; WORK AB Background: Although most depression treat ment outcome scales focus on symptoms, depression also affects daily functioning, social activity, and quality of life. We examined the effects of venlafaxine on social activity, general life functioning, and depressive symptoms in 2 placebo-controlled clinical trials of venlafaxine. Method: Subjects were 600 outpatients with major depression (DSM-III-R criteria). Treatment outcomes were examined separately in each study, primarily because of differing lengths of follow-up. Results: Treatment with venlafaxine significantly improved activity level, general life functioning, and depressive symptoms. Treatment accounted for statistically significant changes in both activity level and general life functioning even after controlling for changes in depression. Conclusion: We provide evidence that social activity is a behavioral domain distinct from depressive symptoms and that venlafaxine improves social activity level and general life functioning in addition to its positive effects on depressive symptoms in outpatients with major depression. C1 Phase V Technol Inc, Wellesley, MA 02181 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Univ Connecticut, Sch Med, Dept Psychiat, Farmington, CT USA. New Britain Gen Hosp, Dept Psychiat, New Britain, CT USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Turner, RR (reprint author), Phase V Technol Inc, 20 Walnut St, Wellesley, MA 02181 USA. NR 52 TC 23 Z9 23 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 1999 VL 60 IS 3 BP 157 EP 163 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 180CR UT WOS:000079368100003 PM 10192590 ER PT J AU Roll, CN Toro, PA Ortola, GL AF Roll, CN Toro, PA Ortola, GL TI Characteristics and experiences of homeless adults: A comparison of single men, single women, and women with children SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article ID DISORDERS; PEOPLE; STRESS; HEALTH; CITY AB Based on a broad sample of 228 homeless adults from throughout Buffalo, New York, single homeless women (n = 56) homeless women with children (n = 41), and single homeless men (n = 131) were compared on a wine range of measures with established reliability and validity Based on total lifetime income from all sources, the poorest of the three groups was the women with children. The two groups of women reported greater psychological distress than the men, had more contact with family members, were more likely to have been recently assaulted, and were less likely to have a history of substance abuse or criminal behavior Although the single men and women reported more stressful life events commonly associated with homelessness than the women with children, the measure used contained few items pertaining to child-rearing. The findings suggest that the three groups examined have different needs and require different interventions. (C) 1999 John Wiley & Sons. Inc. C1 Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Toro, PA (reprint author), Wayne State Univ, Dept Psychol, 71 W Warren Ave, Detroit, MI 48202 USA. NR 34 TC 41 Z9 41 U1 1 U2 9 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0090-4392 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD MAR PY 1999 VL 27 IS 2 BP 189 EP 198 DI 10.1002/(SICI)1520-6629(199903)27:2<189::AID-JCOP6>3.0.CO;2-M PG 10 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 167UZ UT WOS:000078653100006 ER PT J AU Ryu, OH Fincham, AG Hu, CC Zhang, C Qian, Q Bartlett, JD Simmer, JP AF Ryu, OH Fincham, AG Hu, CC Zhang, C Qian, Q Bartlett, JD Simmer, JP TI Characterization of recombinant pig enamelysin activity and cleavage of recombinant pig and mouse amelogenins SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE enamel; matrix; metalloproteinase; enamelysin; amelogenin; MMP-20 ID DEVELOPING BOVINE ENAMEL; PORCINE AMELOGENIN; MATRIX METALLOPROTEINASES; MOLECULAR-CLONING; SEQUENCE; IDENTIFICATION; DOMAIN; PROTEINASES; TRANSCRIPT; INHIBITORS AB Enamelysin (MMP-20) is a tooth-specific matrix metalloproteinase that is initially expressed by ameloblasts and odontoblasts immediately prior to the onset of dentin mineralization, and continues to be expressed throughout the secretory stage of amelogenesis. During the secretory stage, enamel proteins are secreted and rapidly cleaved into a large number of relatively stable cleavage products. Multiple proteinases are present in the developing enamel matrix, and the precise role of enamelysin in the processing of enamel proteins is unknown. We have expressed, activated, and purified the catalytic domain of recombinant pig enamelysin, and expressed a recombinant form of the major secreted pig amelogenin rP172. These proteins were incubated together, and the digestion products were analyzed by SDS-PAGE and mass spectrometric analyses. We assigned amelogenin cleavage products by selecting among the possible polypeptides having a mass within 2 Daltons of the measured values.;The polypeptides identified included the intact protein (amino acids 2-173), as well as 2-148, 2-136, 2-107, 2-105, 2-63, 2-45, 46-148, 46-147, 46-107, 46-105, 64-148, 64-147, and 64-136. These fragments of rP172 include virtually all of the major amelogenin cleavage products observed in vivo. We propose that enamelysin is the predominant proteinase that processes enamel proteins during the secretory phase of amelogenesis. C1 Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, San Antonio, TX 78284 USA. Univ So Calif, Sch Dent, Los Angeles, CA 90033 USA. Forsyth Dent Ctr, Dept Biomineralizat, Boston, MA 02115 USA. RP Simmer, JP (reprint author), Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDCR NIH HHS [DE02848, DE10721, DE11301, R29 DE012098] NR 42 TC 145 Z9 149 U1 0 U2 7 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 1999 VL 78 IS 3 BP 743 EP 750 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 177AD UT WOS:000079184100006 PM 10096449 ER PT J AU Asawanonda, P Taylor, CR AF Asawanonda, P Taylor, CR TI Narrowband (TL-01) UVB phototherapy beyond psoriasis SO JOURNAL OF DERMATOLOGICAL TREATMENT LA English DT Article DE UVB; phototherapy; narrowband; TL-01; ultraviolet ID POLYMORPHIC LIGHT ERUPTION; AIR-CONDITIONED PHOTOTHERAPY; PHOTOCHEMOTHERAPY PUVA; NM; RADIATION; VITILIGO; IRRADIATION; THERAPY; CELLS; SKIN C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Taylor, CR (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,BAR 410, Boston, MA 02114 USA. NR 31 TC 2 Z9 2 U1 0 U2 0 PU MARTIN DUNITZ LTD PI LONDON PA LIVERY HOUSE, 7-9 PRATT ST, LONDON, ENGLAND NW1 0AE SN 0954-6634 J9 J DERMATOL TREAT JI J. Dermatol. Treat. PD MAR PY 1999 VL 10 IS 1 BP 53 EP 57 PG 5 WC Dermatology SC Dermatology GA 186BJ UT WOS:000079706700011 ER PT J AU Zirkin, WM Nadel, ES Brown, DFM Finkel, M Chung, W Griffey, R Shapiro, N Ledbetter, S Wolfe AF Zirkin, WM Nadel, ES Brown, DFM Finkel, M Chung, W Griffey, R Shapiro, N Ledbetter, S Wolfe TI Recurrent pleuritic chest pain SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID LEMIERRE SYNDROME C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAR-APR PY 1999 VL 17 IS 2 BP 329 EP 332 PG 4 WC Emergency Medicine SC Emergency Medicine GA 229DZ UT WOS:000082179400021 PM 10195495 ER PT J AU Sachs, DH AF Sachs, DH TI Immunologic tolerance to organ transplants SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; MIXED ALLOGENEIC CHIMERAS; MAJOR HISTOCOMPATIBILITY COMPLEX; NONLETHAL PREPARATIVE REGIMEN; HUMAN NATURAL ANTIBODIES; RENAL-TRANSPLANTATION; CYNOMOLGUS MONKEYS; RADIATION CHIMERAS; MINIATURE SWINE; IN-VITRO C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Sachs, DH (reprint author), MGH E, CNY 9019,Bldg 149,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [1RO1 AI37692, 1PO1 AI39755] NR 43 TC 5 Z9 5 U1 0 U2 0 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR-APR PY 1999 VL 3 IS 2 BP 105 EP 110 DI 10.1016/S1091-255X(99)80017-1 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 247LU UT WOS:000083222900001 PM 10885945 ER PT J AU Moonka, R Zhou, WG Bell, RH AF Moonka, R Zhou, WG Bell, RH TI Cholecystokinin-A receptor messenger RNA expression in human pancreatic cancer SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE pancreatic neoplasms; in situ hybridization; cholecystokinin ID NUDE-MICE; STIMULATES GROWTH; ANTAGONIST; ADENOCARCINOMA; RAT; LOCALIZATION; INHIBITION; GASTRIN AB Cholecystokinin (CCK) is a gut peptide hormone known to stimulate postprandial gallbladder contraction and pancreatic enzyme secretion. It has also been shown to induce the growth of normal pancreas and of malignant and premalignant lesions in rodents. Although CCK has been shown to promote the growth of human adenocarcinoma cell lines, its rule in the growth of human pancreatic adenocarcinomas in vivo is less clear. Localization of CCK receptors to neoplastic cells within resected human tissue specimens would be suggestive of its potential action as an in vivo promoter of human pancreatic cancer. Resected tissue specimens of pancreatic adenocarcinomas were therefore studied by both reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization for the presence of CCK-A receptors. Ninety percent of studied tumors demonstrated CCK-A expression by RT-PCR, and this expression was localized to neoplastic cells by in situ hybridization. An increase in the expression of CCK receptors is a mechanism by which pancreatic malignancies may gain a significant growth stimulus. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Surg, Seattle Div, Seattle, WA USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. RP Bell, RH (reprint author), MS 112,1660 S Columbian Way, Seattle, WA 98108 USA. NR 33 TC 22 Z9 22 U1 0 U2 0 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR-APR PY 1999 VL 3 IS 2 BP 134 EP 140 DI 10.1016/S1091-255X(99)80022-5 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 247LU UT WOS:000083222900007 PM 10457335 ER PT J AU Dranoff, G AF Dranoff, G TI Interpreting cancer vaccine clinical trials SO JOURNAL OF GENE MEDICINE LA English DT Review DE cancer; vaccines; tumor; immunotherapy; gene transfer; immunologic monitoring; clinical trials ID TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; CYTOTOXIC T-LYMPHOCYTES; IMMUNE-RESPONSE; RANDOMIZED TRIAL; IN-VIVO; MELANOMA; CELLS; ANTIGENS; SURVIVAL AB A number of cancer vaccine strategies have entered initial Phase I clinical testing. In this review, Dr. Glenn Dranoff discusses the prospects that appropriate immunologic monitoring of patients in these trials can help delineate important differences among the various immunization strategies and prioritize the most promising approaches for further clinical development. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAR-APR PY 1999 VL 1 IS 2 BP 80 EP 83 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 251UE UT WOS:000083463600001 PM 10738571 ER PT J AU McDonald, GA Zhu, GM Li, YS Kovesdi, I Wickham, TJ Sukhatme, VP AF McDonald, GA Zhu, GM Li, YS Kovesdi, I Wickham, TJ Sukhatme, VP TI Efficient adenoviral gene transfer to kidney cortical vasculature utilizing a fiber modified vector SO JOURNAL OF GENE MEDICINE LA English DT Article DE adenoviral vector; gene transfer to kidney; alpha(v) integrin ID CYSTIC-FIBROSIS; INTEGRIN; RECEPTORS; ATTACHMENT; BINDING; CELLS AB Background The alpha(v) integrin is present in Vascular endothelium, including that of the kidney. It is also upregulated in the presence of inflammatory cytokines and in some neoplasms. In an effort to transduce vascular endothelial cells, we compare in vitro and in vivo adenoviral gene transfer of a vector with a high affinity peptide ligand to the alpha(v) integrin incorporated into the fiber coat protein AdZ.F(RGD) to an unmodified vector, AdZ. Methods Cell transduction assays were performed on human umbilical vein endothelial cells (HuVEC) and human pulmonary epithelial cells (A549). In vitro competition assays were performed in the presence of either wild type (F5K) or chimeric (F5K(RGD)) soluble recombinant fiber protein. Transduction efficiency was determined by quantitative beta-galactosidase activity. In vivo gene transfer was compared infusing either AdZ or AdZ.F(RGD) into the left renal artery of the rat and assaying beta-galactosidase staining of the kidney. Gene transfer was also evaluated in the presence of a competitive RGD or control RGE peptide. Results There was a marked increase in transgene expression in HuVEC cells with AdZ.F(RGD) as compared to AdZ. The increased expression with AdZ.F(RGD) was more prominent in the endothelial as opposed to the epithelial cell line. Furthermore pre-incubation of these cells with either F5K or F5K(RGD) soluble fiber protein markedly decreased beta-galactosidase activity of AdZ, whereas only the F5K(RGD) decreased beta-galactosidase activity of AdZ.F(RGD). AdZ.F(RGD) also resulted in significantly enhanced beta-galactosidase expression in the vascular endothelium of the kidney (for comparable amounts of virus injected) as well as significantly higher gene transfer to cortical vasculature. Coinfusion of an RGD peptide with AdZ.F(RGD) blocked gene transfer whereas a control RGE peptide did not. Conclusion We conclude that incorporating a high affinity peptide ligand into the adenoviral fiber protein can preferentially enhance in vitro and in vivo adenoviral transfection efficiency in endothelial cells. Enhancing transfection efficiency will not only broaden the scope of disease processes addressed with adenoviral vectors but also allow the use of lower titer, thereby limiting toxicity. This vector has additional potential to transduce endothelial cells within tumors or ischemic tissue where alpha(v) integrins are upregulated. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Beth Israel Deaconnes Med Ctr, Dept Med, Div Renal, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Gen Vec Inc, Rockville, MD 20852 USA. RP Sukhatme, VP (reprint author), Beth Israel Deaconnes Med Ctr, Dept Med, Div Renal, Boston, MA 02215 USA. OI Kovesdi, Imre/0000-0002-0322-3969 NR 21 TC 29 Z9 29 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAR-APR PY 1999 VL 1 IS 2 BP 103 EP 110 DI 10.1002/(SICI)1521-2254(199903/04)1:2<103::AID-JGM16>3.0.CO;2-O PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 251UE UT WOS:000083463600004 PM 10738574 ER PT J AU Fihn, SD AF Fihn, SD TI Specialization by practice location SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Fihn, SD (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 1999 VL 14 IS 3 BP 205 EP 206 DI 10.1046/j.1525-1497.1999.00316.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 179PQ UT WOS:000079338100013 PM 10203631 ER PT J AU Chin, KR Spak, JI Jupiter, JB AF Chin, KR Spak, JI Jupiter, JB TI Septic arthritis and osteomyelitis of the wrist: Reconstruction with a vascularized fibular graft SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE septic; arthritis; osteomyelitis; fibular; graft ID RHEUMATOID-ARTHRITIS AB A case of spontaneous staphylococcus arthritis of the wrist with associated carpal and distal radius osteomyelitis is reported. Following sequential debridements and a 6-week course of parenteral antibiotics, an extensive defect was bridged with a vascularized fibular autograft to achieve a successful fusion. There was no donor site morbidity or recurrent infection. Follow-up radiographs 41 months later demonstrated complete incorporation and hypertrophy of the graft. Copyright (C) 1999 by the American Society for Surgery of the Hand. C1 Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, WACC 527, Boston, MA 02114 USA. RI Spak, Josef/G-9827-2014 NR 18 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 1999 VL 24A IS 2 BP 243 EP 248 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 177GY UT WOS:000079203300007 PM 10194006 ER PT J AU Baskin, DG Schwartz, MW Seeley, RJ Woods, SC Porte, D Breininger, JF Jonak, Z Schaefer, J Krouse, M Burghardt, C Campfield, LA Burn, P Kochan, JP AF Baskin, DG Schwartz, MW Seeley, RJ Woods, SC Porte, D Breininger, JF Jonak, Z Schaefer, J Krouse, M Burghardt, C Campfield, LA Burn, P Kochan, JP TI Leptin receptor long-form splice-variant protein expression in neuron cell bodies of the brain and co-localization with neuropeptide Y mRNA in the arcuate nucleus SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE obesity; food intake; body weight; neuropeptide Y; arcuate nucleus; hypothalamus ID PROOPIOMELANOCORTIN MESSENGER-RNA; OBESE GENE-PRODUCT; BODY-WEIGHT; OB PROTEIN; OB/OB MICE; RAT-BRAIN; MOUSE HYPOTHALAMUS; SUBSTRATE-1 IRS-1; INSULIN; ADIPOSITY AB Reduced leptin (Ob protein) signaling is proposed to be a stimulus for the activation of neuropeptide Y (NPY) gene activity and increased expression of mRNA for the long form of the leptin receptor (Ob-Rb) in the hypothalamic arcuate nucleus. To determine if Ob-Rb protein is expressed in arcuate nucleus NPY neurons, we developed an affinity-purified polyclonal antibody against amino acids 956-1102 of human Ob-Rb. This antibody specifically recognizes the cytoplasmic tail of Ob-Rb and does not react with shorter leptin-receptor variants. Western immunoblots of Ob-Rb-transfected COS cells showed a single 150-kD band, and immunofluorescence revealed intense perinuclear staining in the cytoplasm. A 150-kD band;was also present in Western immunoblots of hypothalamus. Immunocytochemical staining of brain slices revealed immunoreactive Ob-Rb protein concentrated in many neuronal cell bodies in the same regions of the forebrain that also express Ob-Rb mRNA. in the hypothalamus, Ob-Rb-positive cell bodies were abundant in the arcuate nucleus and ventromedial nucleus, with lesser numbers in the dorsomedial nucleus and paraventricular nucleus. Immunostaining was also detected in cell bodies of pyramidal cell neurons of the pyriform cortex and cerebral cortex, in neurons of the thalamus, and on the surface of ependymal cells lining the third ventricle. The choroid plexus, which expresses the short Ob-Ra form, was negative. Combined immunocytochemistry for Ob-Rb protein and fluorescence in situ hybridization for NPY mRNA identified arcuate nucleus neurons containing both NPY mRNA and Ob-Rb protein. The present finding of Ob-Rb protein in neurons that express NPY mRNA supports the hypothesis that arcuate nucleus NPY neurons are direct targets of leptin and play an important role in regulation of food intake and body weight. C1 Vet Affairs Puget Sound Hlth Care Syst, Res Serv, Div Endocrinol & Metab, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Biol Struct, Seattle, WA USA. Univ Washington, Dept Psychol, Seattle, WA USA. Hoffmann La Roche Inc, Dept Metab Dis, Nutley, NJ 07110 USA. RP Baskin, DG (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Res Serv, Div Endocrinol & Metab, Mail Stop 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM baskindg@u.washington.edu FU NIDDK NIH HHS [DK-17047, DK-17844, DK-12829] NR 52 TC 144 Z9 150 U1 0 U2 2 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAR PY 1999 VL 47 IS 3 BP 353 EP 362 PG 10 WC Cell Biology SC Cell Biology GA 168PJ UT WOS:000078701200009 PM 10026237 ER PT J AU Farris, AD Brown, L Reynolds, P Harley, JB James, JA Scofield, RH McCluskey, J Gordon, TP AF Farris, AD Brown, L Reynolds, P Harley, JB James, JA Scofield, RH McCluskey, J Gordon, TP TI Induction of autoimmunity by multivalent immunodominant and subdominant T cell determinants of La (SS-B) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTIBODY-RESPONSE; IMMUNE-RESPONSE; LYMPHOCYTES-B; COMPLEMENT RECEPTOR; DENDRITIC CELLS; GENETIC-CONTROL; SELF-TOLERANCE; MEMORY CELLS; ANTIGEN AB We investigated the consequences of altering the form and valence of defined autodeterminants on the initiation and spreading of experimentally induced La/Ro autoimmunity. Anti-La and Ro (SS-A) Ab responses were monitored following immunization of healthy mice with defined immunodominant and subdominant T cell determinants of the La (SS-B) autoantigen synthesized as either monomeric or multiple antigenic (MAP) peptides, Abs to mouse La (mLa) developed faster and were of higher titer in mice immunized with the subdominant mLa(25-44) MAP compared with mice immunized with the 25-44 monomer, Rapid intermolecular spreading of the autoimmune response to 60-kDa Ro was observed in AKR/J mice immunized with mLa(25-44) MAP, but not in mice immunized repeatedly with monomeric peptide. A/J mice immunized and boosted with the known tolerogenic mLa(287-301) determinant delivered as monomeric peptide failed to develop Abs to either intact mLa or mLa(287-301) peptide. However, immunization with the multivalent mLa(287-301) peptide led to the rapid production of high titer mLa autoantibodies associated with a proliferative T cell response to the mLa(287-301) peptide. The data suggested that the enhanced immunogenicity of MAPs was not due to augmented Ag presentation or T cell stimulation. However, MAP-, but not monomer peptide-, containing immune complexes were potent substrates for Ab-dependent fixation of complement. These results demonstrate that the form of Ag responsible for inducing autoimmunity can profoundly influence the nature and magnitude of the immune response. Thus, molecular mimicry of tolerogenic and nontolerogenic self determinants might trigger autoimmunity under conditions of altered valence. C1 Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. Flinders Med Ctr, Bedford Pk, SA, Australia. Univ Oklahoma, Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Oklahoma City, OK 73104 USA. RP Farris, AD (reprint author), Univ Melbourne, Dept Microbiol & Immunol, Royal Parade, Parkville, Vic 3052, Australia. RI McCluskey, James/A-1291-2007; OI McCluskey, James/0000-0002-8597-815X; Brown, Lorena/0000-0001-9342-909X FU NIAID NIH HHS [AI24717]; NIAMS NIH HHS [AR3584, AR42474] NR 46 TC 30 Z9 30 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 3079 EP 3087 PG 9 WC Immunology SC Immunology GA 168NK UT WOS:000078699000081 PM 10072561 ER PT J AU Jayaraman, A Mansfeld, FB Wood, TK AF Jayaraman, A Mansfeld, FB Wood, TK TI Inhibiting sulfate-reducing bacteria in biofilms by expressing the antimicrobial peptides indolicidin and bactenecin SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE engineered biofilms; biocorrosion; sulfate-reducing bacteria ID BACILLUS-SUBTILIS; PSEUDOMONAS-AERUGINOSA; BOVINE NEUTROPHILS; CATIONIC PEPTIDES; AEROBIC BIOFILMS; GRAMICIDIN-S; CORROSION; STEEL; PREVENTION; GLYCOCALYX AB To identify novel, less-toxic compounds capable of inhibiting sulfate-reducing bacteria (SRB), Desulfovibrio vulgaris and Desulfovibrio gigas in suspension cultures were exposed to several antimicrobial peptides, The bacterial peptide antimicrobials gramicidin S, gramicidin D, and polymyxin B as well as the cationic peptides indolicidin and bactenecin from bovine neutrophils decreased the viability of both SRB by 90% after a 1-h exposure at concentrations of 25-100 mu g ml(-1). To reduce corrosion by inhibiting SRB in biofilms, the genes for indolicidin and bactenecin were expressed in Bacillus subtilis BE1500 and B. subtilis WB600 under the control of the constitutive alkaline protease (apr) promoter, and the antimicrobials were secreted into the culture medium using the apr signal sequence. Bactenecin was also synthesized and expressed as a fusion to the pro-region of barnase from Bacillus amyloliquefaciens. Concentrated culture supernatants of B. subtilis BE1500 expressing bactenecin at 3 mu g ml(-1) decreased the viability of Escherichia coli BK6 by 90% and the reference SRB D. vulgaris by 83% in suspension cultures, B. subtilis BE1500 and B. subtilis WB600 expressing bactenecin in biofilms also inhibited the SRB-induced corrosion of 304 stainless steel six to 12-fold in continuous reactors as evidenced by the lack of change in the impedance spectra (resistance polarization) upon addition of SRB and by the reduction in hydrogen sulfide and iron sulfide in batch fermentations with mild steel. A 36-fold decrease in the population of D. vulgaris in a B. subtilis BE1500 biofilm expressing bactenecin was also observed, This is the first report of an antimicrobial produced in a biofilm for in vivo applications and represents the first application of a beneficial, genetically-engineered biofilm for combating corrosion. C1 Univ Connecticut, Dept Chem Engn, Storrs, CT 06269 USA. Univ So Calif, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wood, TK (reprint author), Univ Connecticut, Dept Chem Engn, Storrs, CT 06269 USA. OI Wood, Thomas/0000-0002-6258-529X NR 40 TC 45 Z9 47 U1 0 U2 15 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD MAR PY 1999 VL 22 IS 3 BP 167 EP 175 DI 10.1038/sj.jim.2900627 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 206MT UT WOS:000080883900008 ER PT J AU Clark, RA AF Clark, RA TI Activation of the neutrophil respiratory burst oxidase SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Interplantary-Society Conference CY MAY 30-JUN 02, 1997 CL PORT LUDLOW, WASHINGTON SP Interplanetary Soc ID CHRONIC GRANULOMATOUS-DISEASE; CELL-FREE SYSTEM; ADENINE-DINUCLEOTIDE PHOSPHATE; PHAGOCYTE NADPH OXIDASE; CYTOCHROME-B; BINDING SITE; SUBCELLULAR-LOCALIZATION; MICROBICIDAL OXIDASE; CYTOSOLIC COMPONENTS; PLASMA-MEMBRANE AB The neutrophil respiratory burst oxidase is a multicomponent activatable enzyme comprising one of the major phagocyte antimicrobial systems. In the genetic disorder chronic granulomatous disease, absent oxidase function is associated with recurrent, severe, and often life-threatening infections. The components of the oxidase system include both membrane-bound and soluble cytosolic proteins. A primary feature of stimulus-dependent activation is the translocation of a complex of cytosolic factors to the membrane, where they associate with a flavocytochrome enzyme. Interactions among the various oxidase components occur through a number of specific regions, including SH3 domains and proline-rich motifs. The fully assembled complex functions as an electron transport system, moving electrons from cytosolic NADPH to molecular oxygen to form superoxide, which, along with subsequent reactive products, exerts microbicidal and cytotoxic activities. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Clark, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIAID NIH HHS [AI-20866, R01 AI020866, R37 AI020866] NR 37 TC 75 Z9 76 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1999 VL 179 SU 2 BP S309 EP S317 DI 10.1086/513849 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 202DT UT WOS:000080637400007 PM 10081501 ER PT J AU Radakovic-Fijan, S Rappersberger, K Tanew, A Honigsmann, H Ortel, B AF Radakovic-Fijan, S Rappersberger, K Tanew, A Honigsmann, H Ortel, B TI Ultrastructural changes in PAM cells after photodynamic treatment with delta-aminolevulinic acid-induced porphyrins or photosan SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE delta-aminolevulinic acid; mitochondrial activity; photodynamic therapy; Photosan; ultrastructure ID ENDOGENOUS PORPHYRINS; PHOTOFRIN-II; PROTOPORPHYRIN-IX; THERAPY; PHOTOSENSITIZATION; LYSOSOMES; HEMATOPORPHYRIN; DESFERRIOXAMINE; ACCUMULATION; FIBROBLASTS AB Photodynamic therapy (PDT) is the combination of a photosensitizing drug (Ps) with light in the presence of oxygen leading to the generation of reactive molecular species and destruction of cancer cells. In this study we compared PDT with two Ps, the hematoporphyrin derivative Photosan (Ph) and delta-aminolevulinic acid (ALA)-induced endogenous protoporphyrin IX, with respect to mitochondrial function and ultrastrucural alterations. The effects of PDT were investigated in PAM 212 cells after different Ps incubation times, light doses, and post-treatment periods, Both Ps induced a Light dose-dependent impairment of the mitochondrial function with the dose-response curve being steep for ALA and flat for Ph, The prolongation of the incubation time from 4 to 20 h resulted in an increased reduction of mitochondrial activity after ALA PDT but not after Ph PDT, Treatment with an irradiation dose that decreased mitochondrial activity by 50% (IC50) led to early and profound changes of mitochondrial morphology in ALA photosensitized cells, whereas photosensitization with Ph resulted in more pronounced alterations of lysosomes, We conclude that at bioequivalent sublethal PDT exposures of PAM 212 cells, ALA-induced damage is primarily restricted to mitochondria, whereas Ph-induced cytotoxicity is mediated by damage of the lysosomal system. C1 Univ Vienna, Sch Med, Dept Dermatol, Div Special & Environm Dermatol, A-1090 Vienna, Austria. Univ Vienna, Div Gen Dermatol, A-1090 Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Radakovic-Fijan, S (reprint author), Univ Vienna, Sch Med, Dept Dermatol, Div Special & Environm Dermatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. NR 29 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1999 VL 112 IS 3 BP 264 EP 270 DI 10.1046/j.1523-1747.1999.00533.x PG 7 WC Dermatology SC Dermatology GA 172KF UT WOS:000078921500002 PM 10084300 ER PT J AU Eming, SA Whitsitt, JS He, L Krieg, T Morgan, JR Davidson, JM AF Eming, SA Whitsitt, JS He, L Krieg, T Morgan, JR Davidson, JM TI Particle-mediated gene transfer of PDGF isoforms promotes wound repair SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE alternative splicing; gene therapy; growth factor; wound healing ID GROWTH FACTOR-BETA; EXTRACELLULAR-MATRIX; FACTOR-BB; ADENOVIRUS VECTORS; PRESSURE ULCERS; EXPRESSION; FIBROBLASTS; PROTEINS; TISSUE; CHAIN AB Several techniques for cutaneous gene transfer have been investigated for either in vitro or in vivo applications, In the present study, we investigated whether the direct delivery of platelet-derived growth factor cDNA into skin results in improvement in tissue repair. Cutaneous transfections were carried out in rats using a particle-bombardment device (Accell), As revealed by reverse transcriptase-polymerase chain reaction, transgene expression in vivo was transient, with low level expression by day 5, When compared with wounds transfected with a control cytomegalovirus-luciferase plasmid, wounds transfected with platelet-derived growth factor A or B in the MFG vector showed a significant increase in wound tensile strength 7 and 14 d after transfection. At both time points platelet-derived growth factor A transfected wounds exhibited the highest increase in tensile strength over controls, resulting in a 3.5-fold increase at day 7 and a 1.5-fold increase at day 14, The degree of stimulation was not remarkably different between wounds transfected with platelet-derived growth factor B, which is predominantly cell associated, or a truncation mutant, platelet-derived growth factor B211, which is predominantly secreted. These findings demonstrate that in vivo gene transfer by particle bombardment can be used to improve the tissue repair response. This approach provides a robust tool to assess the biologic activity of various proteins and will aid in the development of therapeutic cutaneous gene delivery. C1 Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. Univ Cologne, Dept Dermatol, D-5000 Cologne, Germany. Vet Affairs Med Ctr, Res Serv, Nashville, TN 37212 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burns Inst, Boston, MA USA. RP Davidson, JM (reprint author), Vanderbilt Univ, Sch Med, Dept Pathol, C-3321 MCN,21st St & Garland St, Nashville, TN 37232 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIA NIH HHS [AG-06528]; NIAMS NIH HHS [AR42012-01A1]; NICHD NIH HHS [P01 HD28528-01] NR 40 TC 83 Z9 91 U1 0 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1999 VL 112 IS 3 BP 297 EP 302 DI 10.1046/j.1523-1747.1999.00522.x PG 6 WC Dermatology SC Dermatology GA 172KF UT WOS:000078921500007 PM 10084305 ER PT J AU D'Auria, J Porte, D AF D'Auria, J Porte, D TI The JIM interview: Daniel Porte, Jr, MD SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1999 VL 47 IS 3 BP 101 EP 105 PG 5 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 181JG UT WOS:000079437800007 ER PT J AU Escary, JL Choy, HA Reue, K Wang, XP Castellani, LW Glass, CK Lusis, AJ Schotz, MC AF Escary, JL Choy, HA Reue, K Wang, XP Castellani, LW Glass, CK Lusis, AJ Schotz, MC TI Paradoxical effect on atherosclerosis of hormone-sensitive lipase overexpression in macrophages SO JOURNAL OF LIPID RESEARCH LA English DT Article DE cholesteryl-ester hydrolysis; acyl-CoA : cholesterol acyltransferase; foam cells; aortic lesions; transgenic mice ID CYTOPLASMIC CHOLESTERYL ESTERS; HIGH-DENSITY LIPOPROTEIN; ACYL-COENZYME-A; GENE-EXPRESSION; ACAT INHIBITOR; FOAM CELLS; ACYLTRANSFERASE; LESIONS; TISSUE; HYDROLYSIS AB Foam cells formed from receptor-mediated uptake of lipoprotein cholesterol by macrophages in the arterial intima are critical in the initiation, progression, and stability of atherosclerotic lesions. Macrophages accumulate cholesterol when conditions favor esterification by acyl-CoA:cholesterol acyltransferase (ACAT) over cholesterylester hydrolysis by a neutral cholesteryl-ester hydrolase, such as hormone-sensitive lipase (HSL), and subsequent cholesterol efflux mediated by extracellular accepters, We recently made stable transfectants of a murine macrophage cell line, RAW 264.7, that overexpressed a rat HSL cDNA and had a 5-fold higher rate of cholesteryl-ester hydrolysis than control cells. The current study examined the effect of macrophage-specific HSL overexpression on susceptibility to diet-induced atherosclerosis in mice. A transgenic Line overexpressing the rat HSL cDNA regulated with a macrophage-specific scavenger receptor promoter-enhancer was established by breeding with C57BL/6J mite. Transgenic peritoneal macrophages exhibited macrophage-specific 7-fold overexpression of HSL cholesterol esterase activity, Total plasma cholesterol levels in transgenic mice fed a chow diet were modestly elevated 16% compared to control littermates, After 14 weeks on a high-fat, high-cholesterol diet, total cholesterol increased 3-fold, with no difference between transgenics and controls, However, HSL overexpression resulted in thicker aortic fatty lesions that were 2.5-times larger in transgenic mice. HSL expression in the aortic lesions was shown by immunocytochemistry, Atherosclerosis was more advanced in transgenic mice exhibiting raised lesions involving the aortic wall, along with lipid accumulation in coronary arteries occurring only in transgenics, Thus, increasing cholesteryl-ester hydrolysis, without concomitantly decreasing ACAT activity or increasing cholesterol efflux, is not sufficient to protect against atherocsclerosis.-Escary, J-L., H. A. Choy, K. Reue, X-P. Wang, L. W. Castellani, C, K. Glass, A.J. Lusis, and M. C. Schotz. Paradoxical effect on atherosclerosis of hormone-sensitive lipase overexpression in macrophages. J. Lipid Res. 1999. C1 W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Inst Mol Biol, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Dept Microbiol & Mol Genet, Los Angeles, CA 90095 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. RP Schotz, MC (reprint author), W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL14197, HL28481] NR 27 TC 39 Z9 40 U1 0 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 1999 VL 40 IS 3 BP 397 EP 404 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 173EG UT WOS:000078967800004 PM 10064727 ER PT J AU Myers, SM Salomon, R Goessling, A Pelet, A Eng, C von Deimling, A Lyonnet, S Mulligan, LM AF Myers, SM Salomon, R Goessling, A Pelet, A Eng, C von Deimling, A Lyonnet, S Mulligan, LM TI Investigation of germline GFR alpha-1 mutations in Hirschsprung disease SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE RET; Hirschsprung disease; GFR alpha-1; GDNF ID NEUROTROPHIC FACTOR GDNF; MICE LACKING GDNF; C-RET PROTOONCOGENE; TYROSINE KINASE; RECEPTOR; EXPRESSION; ALPHA; NEURTURIN; ACTIVATION; PHENOTYPE AB Inactivating mutations of the RET protooncogene and of one of its soluble ligand molecules, glial cell line derived neurotrophic factor (GDNF), have been found in a subset of patients with Hirschsprung disease (HSCR). However, the majority of HSCR mutations remain unidentified. As normal RET function requires a multicomponent ligand complex for activation, other members of the RET ligand complex are primary candidates for these mutations. We investigated the presence of mutations in another member of the RET signalling complex, GDNF family receptor alpha-1 (GFR alpha-1), in a panel of 269 independent cases of HSCR. We identified 10 polymorphisms at the GFRa-1 locus. Surprisingly, however, we did not identify any sequence variants in our HSCR population that were not also present in a normal control population. Our data suggest that mutations of the GFR alpha-1 gene are not a common aetiological event in HSCR. C1 Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Paediat, Kingston, ON K7L 3N6, Canada. Hop Enfants Malad, Tour Tech Lavoisier, F-75743 Paris, France. Univ Kliniken Bonn, Inst Neuropathol, D-53105 Bonn, Germany. Dana Farber Canc Inst, Translat Res Lab, Charles A Dana Human Canc Genet Unit, Susan & Richard Smith Labs, Boston, MA 02115 USA. RP Mulligan, LM (reprint author), Queens Univ, Dept Pathol, 20 Barrie St, Kingston, ON K7L 3N6, Canada. RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X NR 32 TC 29 Z9 30 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD MAR PY 1999 VL 36 IS 3 BP 217 EP 220 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 175MM UT WOS:000079098300009 PM 10204848 ER PT J AU Wakita, T Moradpour, D Tokushihge, K Wands, JR AF Wakita, T Moradpour, D Tokushihge, K Wands, JR TI Antiviral effects of antisense RNA on hepatitis C virus RNA translation and expression SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 03-07, 1995 CL CHICAGO, ILLINOIS SP Amer Assoc Study Liver Dis DE antisense RNA; hepatitis C; core-luciferase fusion ID NON-B-HEPATITIS; NON-A; GENE-EXPRESSION; HEPATOCELLULAR-CARCINOMA; INHIBITION; OLIGODEOXYNUCLEOTIDES; CELLS; ASSAY; OLIGONUCLEOTIDE; TRANSFUSION AB We developed approaches using antisense RNA to inhibit hepatitis C virus (HCV) RNA translation and HCV core protein expression. An HCV genotype 1b cDNA comprising nt 1-1321 or a fusion construct consisting of HCV (nt 1-584) and luciferase cDNAs were inserted downstream of T7 and CMV promoter sequences and used to generate HCV RNA target molecules. Such constructs will produce HCV core or HCV core-luciferase fusion proteins in vitro or within transfected cells. Seven different antisense RNA constructs were designed to target the highly conserved 5' region of HCV RNA at nt positions 1-402. For in vitro experiments, synthesized HCV RNA target sequences and antisense RNAs were mixed at various molar ratios and subsequently translated in a rabbit reticulocyte lysate system. In cell culture studies, the HCV core-luciferase fusion cDNA was co-transfected with antisense RNA-producing constructs into human hepatocellular carcinoma (HCC) cells. Luciferase activity in cell lysates was measured to determine quantitatively antiviral effects within the cell. It was found that translation of HCV RNAs was efficiently inhibited by antisense RNA in vitro. The specificity of this inhibition was confirmed using control target RNA sequences or nonrelevant antisense RNA constructs. Co-transfection studies demonstrated that antisense RNA inhibited HCV core-luciferase fusion protein expression by 41-57% in HuH-7 HCC cells. These studies indicate that antisense RNA will find viral target RNA sequences in HuH-7 cells and inhibit HCV RNA translation. More important, these studies have defined critical viral RNA target sequences susceptible to antisense inhibitory effects within the cell. J. Med. Virol. 57:217-222, 1999. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Mol Hepatol Lab, Charlestown, MA 02129 USA. Tokyo Metropolitan Inst Med Sci, Dept Microbiol, Tokyo 113, Japan. Univ Hosp Freiburg, Dept Med 2, Freiburg, Germany. Tokyo Womens Med Coll, Inst Gastroenterol, Div Med, Tokyo 162, Japan. RP Wands, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Mol Hepatol Lab, 149 13th St, Charlestown, MA 02129 USA. EM wands@helix.mgh.harvard.edu FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 30 TC 19 Z9 23 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAR PY 1999 VL 57 IS 3 BP 217 EP 222 DI 10.1002/(SICI)1096-9071(199903)57:3<217::AID-JMV1>3.0.CO;2-X PG 6 WC Virology SC Virology GA 162MZ UT WOS:000078351900001 PM 10022790 ER PT J AU Kaysen, JH Campbell, WC Majewski, RR Goda, FO Navar, GL Lewis, FC Goodwin, TJ Hammond, TG AF Kaysen, JH Campbell, WC Majewski, RR Goda, FO Navar, GL Lewis, FC Goodwin, TJ Hammond, TG TI Select de novo gene and protein expression during renal epithelial cell culture in rotating wall vessels is shear stress dependent SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE flow cytometry; antisense oligos; microgravity; astrobiology; differential display ID SIMULATED MICROGRAVITY; TERATOGENIC ANTIBODIES; RECEPTOR; IDENTIFICATION; COCULTURE; COMPLEX; VILLIN; TARGET; FORM AB The rotating wall vessel has gained popularity as a clinical cell culture tool to produce hormonal implants. It is desirable to understand the mechanisms by which the rotating wall vessel induces genetic changes, if we are to prolong the useful life of implants. During rotating wall vessel culture gravity is balanced by equal and opposite hydrodynamic forces including shear stress. The current study provides the first evidence that shear stress response elements, which modulate gene expression in endothelial cells, are also active in epithelial cells. Rotating wall culture of renal cells changes expression of select gene products including the giant glycoprotein scavenger receptors cubulin and megalin, the structural microvillar protein villin, and classic shear stress response genes ICAM, VCAM and MnSOD. Using a putative endothelial cell shear stress response element binding site as a decoy, we demonstrate the role of this sequence in the regulation of selected genes in epithelial cells. However, many of the changes observed in the rotating wall vessel are independent of this response element. It remains to define other genetic response elements modulated during rotating wall vessel culture, including the role of hemodynamics characterized by 3-dimensionality, low shear and turbulence, and cospatial relation of dissimilar cell types. C1 Tulane Xavier Ctr Bioenvironm Res, Dept Med, Nephrol Sect, New Orleans, LA 70112 USA. Tulane Xavier Ctr Bioenvironm Res, Tulane Environm Astrobiol Ctr, New Orleans, LA 70112 USA. Tulane Univ, Med Ctr, Dept Surg, New Orleans, LA 70112 USA. Vet Adm Med Ctr, New Orleans, LA 70146 USA. Univ Wisconsin Hosp & Clin, Madison, WI 53705 USA. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. RP Hammond, TG (reprint author), Tulane Xavier Ctr Bioenvironm Res, Dept Med, Nephrol Sect, 1430 Tulane Ave, New Orleans, LA 70112 USA. FU NCRR NIH HHS [R21 RR12645]; NIDDK NIH HHS [DK46117] NR 38 TC 37 Z9 38 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD MAR 1 PY 1999 VL 168 IS 1 BP 77 EP 89 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 173EV UT WOS:000078969000008 PM 10051691 ER PT J AU Schultze, JL Nadler, LM AF Schultze, JL Nadler, LM TI T cell mediated immunotherapy for B cell lymphoma SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE vaccination; lymphoma; CD40; CTL; idiotype ID BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; ANTIGEN-PRESENTING CELL; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SURFACE-IMMUNOGLOBULIN IDIOTYPE; RESTRICTED TUMOR-ANTIGENS; IN-VIVO EXPRESSION; MHC CLASS-I AB Increasing evidence suggests that chemotherapy does not cure the majority of patients with B cell non-Hodgkin's lymphoma (NHL). Therefore new treatment modalities are necessary. Immunotherapy of B cell lymphomas using monoclonal antibodies has been shown to be efficacious in murine model systems and also in patients. With the identification of tumor-specific antigens as targets for autologous T cells, T cell mediated immunity has been revived as an immunotherapeutic modality in B cell lymphomas. For B cell lymphomas the lymphoma-specific idiotype can be used as a tumor-specific antigen to stimulate T cells. Alternatively, the malignant B cells can be modified to become efficient antigen-presenting cells and present peptides from their own tumor-specific antigens to the autologous T cells. Here we discuss previous and currently explored immunotherapeutic strategies for B cell lymphoma. C1 Harvard Univ, Sch Med, Dept Adult Oncol,Dana Farber Canc Inst, Dis Ctr Hematol Malignancies,Dept Med, Boston, MA 02115 USA. RP Schultze, JL (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol,Dana Farber Canc Inst, Dis Ctr Hematol Malignancies,Dept Med, Boston, MA 02115 USA. EM schultze@mbcrr.harvard.edu RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 134 TC 22 Z9 25 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD MAR PY 1999 VL 77 IS 3 BP 322 EP 331 DI 10.1007/s001090050358 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 166WB UT WOS:000078599800004 PM 10090595 ER PT J AU Blais, MA Hilsenroth, MJ Fowler, JC AF Blais, MA Hilsenroth, MJ Fowler, JC TI Diagnostic efficiency and hierarchical functioning of the DSM-IV borderline personality disorder criteria SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID III-R; VALIDITY; SEARCH AB This study presents information regarding the diagnostic efficiency and hierarchical functioning of the newly revised DSM-IV borderline personality disorder (BPD) criteria. Past research using the DSM-III-R version of BPD showed that the individual BPD criteria differ greatly in their diagnostic utility and that in some clinical situations, fewer than five of eight criteria could efficiently make the diagnosis. Two groups of inpatients, a BPD group (N = 33) and a non-BPD group (N = 43), were rated on the DSM-IV BPD criteria. Acceptable interrater reliability (Kappa estimates) was obtained for the presence or absence of the nine individual BPD criteria. Diagnostic efficiency statistics, sensitivity, specificity, false positive and false negative rates, positive predictive power, negative predictive power, overall classification rate and Kappa with the clinical diagnosis were obtained for all nine BPD criteria. The diagnostic efficiency data indicated that BPD criteria 1 (abandonment) and 2 (unstable relationships) functioned best in our inpatient sample, whereas criterion 9 (stress-related paranoia) performed the poorest. A stepwise logistic regression showed that the combination of BPD criteria 2, 1, 6 (unstable affect), and 3 (identity) (presented in their order of entry into the regression equation) provided the best prediction of group membership (BPD or non-BPD). The results suggest that a further refinement of both the BPD criteria set and the diagnostic decision rules may be needed. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Arkansas, Dept Psychol, Fayetteville, AR 72701 USA. Austen Riggs Ctr, Stockbridge, MA USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Warren 1220,55 Fruit St, Boston, MA 02114 USA. NR 47 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 1999 VL 187 IS 3 BP 167 EP 173 DI 10.1097/00005053-199903000-00006 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 176EZ UT WOS:000079139500006 PM 10086473 ER PT J AU Velte, TJ Masland, RH AF Velte, TJ Masland, RH TI Action potentials in the dendrites of retinal ganglion cells SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NEURONS; PROPAGATION; INITIATION; CHANNELS; LIGHT AB The somas and dendrites of intact retinal ganglion cells were exposed by enzymatic removal of the overlying endfeet of the Muller glia. Simultaneous whole cell patch recordings were made from a ganglion cell's dendrite and the cell's soma. When a dendrite was stimulated with depolarizing current, impulses often propagated to the soma, where they appeared as a mixture of small depolarizations and action potentials. When the soma was stimulated, action potentials always propagated back through the dendrite. The site of initiation of action potentials, as judged by their timing, could be shifted between soma and dendrite by changing the site of stimulation. Applying QX-314 to the soma could eliminate somatic action potentials while leaving dendritic impulses intact. The absolute amplitudes of the dendritic action potentials varied somewhat at different distances from the soma, and it is not clear whether these variations an real or technical. Nonetheless, the qualitative experiments clearly suggest that the dendrites of retinal ganglion cells generate regenerative Na+ action potentials, at least in response to large diner depolarizations. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 429, Boston, MA 02114 USA. NR 26 TC 52 Z9 54 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1999 VL 81 IS 3 BP 1412 EP 1417 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 178AB UT WOS:000079242300043 PM 10085366 ER PT J AU Mendez, MF Nakawatase, TV Brown, CV AF Mendez, MF Nakawatase, TV Brown, CV TI Involuntary laughter and inappropriate hilarity SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the American-Neuropsychiatric-Association CY FEB 01-03, 1998 CL HONOLULU, HAWAII SP Amer Neruopsychiat Assoc ID PATHOLOGICAL LAUGHTER; ANGELMAN SYNDROME; GELASTIC SEIZURES; HYPOTHALAMIC HAMARTOMAS; SURGICAL-TREATMENT; EEG; INFARCTION; EPILEPSY; SYMPTOM; DISEASE AB Laughter is It particularly human behavior. Neuropsychiatrists are faced with disorders of laughter, yet the nature of this behavior and its disturbances remains obscure. The authors report an unusual patient with involuntary and unremitting laughter for 20 years and review the literature. The nature of laughter suggests that it has a unique role in human communication, particularly in the social exploration of incongruous information. The disorders of laughter suggest 17 neuroanatomical circuitry that includes the anterior cingulate gyrus, caudal hypothalamus, temporal-amygdala structures, and 17 pontomedullary center. Treatment includes the use of antidepressant and antimanic agents for disorders of laughter. C1 Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Neurobehav Unit, Dept Neurol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Neurobehav Unit, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Neurobehav Unit, Dept Nucl Med, Los Angeles, CA 90073 USA. RP Mendez, MF (reprint author), Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Neurobehav Unit, Dept Neurol, 11301 Wilshire Blvd,691-116AF, Los Angeles, CA 90073 USA. NR 47 TC 22 Z9 23 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1999 VL 11 IS 2 BP 253 EP 258 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 194QE UT WOS:000080204400009 PM 10333997 ER PT J AU Mendez, MF Younesi, FL Perryman, KM AF Mendez, MF Younesi, FL Perryman, KM TI Use of donepezil for vascular dementia: Preliminary clinical experience SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ALZHEIMERS-DISEASE; SYMPTOMS; CRITERIA; TACRINE C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit, 11301 Wilshire Blvd,116AF, Los Angeles, CA 90073 USA. NR 15 TC 41 Z9 47 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1999 VL 11 IS 2 BP 268 EP 270 PG 3 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 194QE UT WOS:000080204400011 PM 10333999 ER PT J AU Zajkowski, MD Mitchell, TA Hudson, JW AF Zajkowski, MD Mitchell, TA Hudson, JW TI Chronic mandibular pain and drainage SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DIFFUSE SCLEROSING OSTEOMYELITIS; FLORID OSSEOUS DYSPLASIA C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. Univ Tennessee, Med Ctr, Dept Oral & Maxillofacial Surg, Knoxville, TN USA. RP Zajkowski, MD (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,ACC 230, Boston, MA 02114 USA. NR 7 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 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 1999 VL 57 IS 3 BP 321 EP 324 DI 10.1016/S0278-2391(99)90681-X PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 173MC UT WOS:000078983500019 PM 10077204 ER PT J AU Scrivani, SJ Chaudry, A Maciewicz, RJ Keith, DA AF Scrivani, SJ Chaudry, A Maciewicz, RJ Keith, DA TI Chronic neurogenic facial pain: Lack of response to intravenous phentolamine SO JOURNAL OF OROFACIAL PAIN LA English DT Article DE facial pain; neurogenic pain; phentolamine; lidocaine ID REFLEX SYMPATHETIC DYSTROPHY; PERIPHERAL-NERVE INJURY; MAINTAINED PAIN; NEUROPATHIC PAIN; MECHANISMS; ACTIVATION; AFFERENTS; CAUSALGIA; NEURONS; RAT AB Aims: Chronic neurogenic facial pain is commonly resistant to treatment and is often the source of significant patient morbidity. Adrenergic mechanisms are postulated to play a role in producing this type of pain, and adrenergic blocking agents are frequently used in clinical practice for pain control therapy. The analgesic effectiveness of an adrenergic blocking agent, intravenous phentolamine, was compared to saline and intravenous lidocaine in the present study using a single-blind protocol in patients with chronic neurogenic facial pain. Methods: Thirty patients were studied whose common clinical features included pain for more than 6 months, unilateral trigeminal distribution, constant dysesthesia, and no evidence of pathology or known etiology. Phentolamine (30 mg), lidocaine (100 mg), and saline were each infused over periods of 5 to 10 minutes. Pain ratings were assessed every 4 minutes throughout each study period using a 10-point pain intensity scale. Results: No patient reported subjective improvement of pain during or immediately following phentolamine or saline infusions alone. Sixteen of the 30 patients reported decreased pain following lidocaine infusion. In the majority of the patients, the duration of lidocaine analgesia was less than 30 minutes; however, some patients reported decreased pain for a longer time. Conclusion: The results do not support an adrenergic mechanism for chronic neurogenic facial pain. The response to lidocaine, a nonadrenergic, membrane-stabilizing agent, suggests that it may have clinical effectiveness in certain neurogenic facial pain patients. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Cambridge, MA 02138 USA. Tufts Univ, New England Med Ctr, Gelb Pain Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Craniofacial Pain Ctr, Boston, MA 02114 USA. Harvard Vanguard Med Associates, Boston, MA USA. RP Scrivani, SJ (reprint author), New York Presbyterian Hosp, Columbia Presbyterian Med Ctr, Ctr Oral Facial & Head Pain, Dept Oral & Maxillofacial Surg, HP-8,622 W 168th St, New York, NY 10032 USA. NR 58 TC 11 Z9 11 U1 0 U2 0 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 1064-6655 EI 1945-3396 J9 J OROFAC PAIN JI J. Orofac. Pain PD SPR PY 1999 VL 13 IS 2 BP 89 EP 96 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 194ZT UT WOS:000080225200004 PM 10425980 ER PT J AU Boyan, BD Caplan, AI Heckman, JD Lennon, DP Ehler, W Schwartz, Z AF Boyan, BD Caplan, AI Heckman, JD Lennon, DP Ehler, W Schwartz, Z TI Osteochondral progenitor cells in acute and chronic canine nonunions SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID MESENCHYMAL STEM-CELLS; GROWTH-FACTOR-BETA; BONE MORPHOGENETIC PROTEIN; IN-VITRO; ALKALINE-PHOSPHATASE; OSTEOGENIC CELLS; MARROW; DIFFERENTIATION; CHONDROCYTES; EXPRESSION AB This study examined the ability of cells isolated from early healing segmental defects and from tissue from chronic nonunions to support bone and cartilage formation In vivo and their response to transforming growth factor-betal in vitro. Ostectomies (3 mm) were created in the radial diaphysis of four dogs. The dogs were splinted 3-5 days postoperatively and then allowed to bear full weight. At 7 days, tissue in the defect was removed and any periosteum was discarded; cells in the defect tissue were released by enzymatic digestion. The dogs were splinted again and allowed to bear full weight for 12 weeks. Radiographs confirmed a persistent nonunion in each dog. Defect tissue was again removed, any periosteum was discarded, and cells were isolated. Cells were also obtained from the defect tissue by nonenzymatic means with use of explant cultures. One-half of the tissue and one-half of any preconfluent, first-passage cultures were shipped to Cleveland by overnight carrier. At second passage, cells were loaded into ceramic cubes and implanted into immunocompromised mice for 3 or 6 weeks. Harvested cubes were examined histologically for cartilage and bone with use of a semiquantitative scoring system. Confluent fourth-passage cultures of 7 and 84-day defect tissue cells were cultured with 0.03-0.88 ng/ml transforming growth factor-betal for 24 hours, and [H-3]thymi dine incorporation and alkaline phosphatase specific activity were determined. Donor-dependent differences were noted in the rate at which defect cells achieved confluence; in general, cells from 7-day tissue divided most rapidly. Seven-day defect cells formed less bone and at a slower rate than was seen in the ceramic cubes containing samples from day 84. Cells derived enzymatically behaved similarly to those from explant cultures. Ceramic cubes contained fibrous connective tissue, cartilage, bone, and fat, indicating that multipotent cells were present, Stimulation of [H-3]thymidine incorporation in response to transforming growth factor-betal was donor dependent and variable; only two of six separate isolates of cells exposed to it had measurable alkaline phosphatase activity (which was relatively low), and none of the cultures exhibited an increase in response to transforming growth factor-betal for 24 hours. This indicates that mesenchymal progenitor cells are present in the healing defect tissue at 7 and 84 days and that the relative proportion of osteochondroprogenitor cells is greater at the later time. The response to transforming growth factor-betal is typical of multipotent mesenchymal cells but not of committed chondrocytes or osteoblasts, indicating that these committed and differentiated cells are not present in early stages of healing and suggesting that their differentiation is inhibited in chronic nonunion. C1 Univ Texas, Hlth Sci Ctr, Dept Orthopaed, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Periodont, San Antonio, TX 78284 USA. Case Western Reserve Univ, Skeletal Res Inst, Cleveland, OH 44106 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Jerusalem, Israel. RP Boyan, BD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Orthopaed, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIDCR NIH HHS [DE-07220, DE-08603] NR 64 TC 33 Z9 35 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAR PY 1999 VL 17 IS 2 BP 246 EP 255 DI 10.1002/jor.1100170214 PG 10 WC Orthopedics SC Orthopedics GA 188GM UT WOS:000079838500013 PM 10221842 ER PT J AU Tatsuta, N Suzuki, N Koya, K Kawakami, M Shishido, T Chen, LB AF Tatsuta, N Suzuki, N Koya, K Kawakami, M Shishido, T Chen, LB TI Determination of MKT-077, a novel antineoplastic agent, in plasma samples by high-performance liquid chromatography and its application to pharmacokinetics in rats SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE MKT-077; delocalized lipophilic cation; reverse-phase liquid chromatography; rat plasma; pharmacokinetics; antineoplastic ID MITOCHONDRIAL AB A simple high-performance liquid chromatographic method was developed for determination of a novel antineoplastic agent MKT-077 in plasma. MKT-077 was extracted from 50 mu l of plasma with acetonitrile containing 1 mi trifluoroacetic acid per liter. Chromatographic separation was achieved within 13.5 min using a reverse-phase Puresil C-18 analytical column. A visible detector operated at 490 nm was used. The linearity of the calibration curve was obtained (r(2) = 0.99986) over the analytical range of 10-500 ng ml(-1). The intra- and inter-assay precision was in the range of 0.9-11.1 and 0.3-4.4%, respectively. The intra- and inter-assay bias ranged from - 7.3 to 11.1% and from 0.4 to 11.6%, respectively. The utility of this assay was demonstrated after the administration of a single dose of MKT-077 to rats. The plasma elimination half-life of MKT-077 was 1.8-4 h. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Fuji Photo Film Co Ltd, Ashigara Res Labs, Kanagawa 25001, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tatsuta, N (reprint author), Shionogi Biores, 45 Hartwell Ave, Lexington, MA 02421 USA. EM tatsuta@erols.com NR 6 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD MAR PY 1999 VL 19 IS 3-4 BP 423 EP 428 DI 10.1016/S0731-7085(98)00183-6 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 165YH UT WOS:000078549100017 PM 10704107 ER PT J AU Xie, AL Skatrud, JB Puleo, DS Morgan, BJ AF Xie, AL Skatrud, JB Puleo, DS Morgan, BJ TI Arousal from sleep shortens sympathetic burst latency in humans SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID HUMAN MUSCLE NERVES; BLOOD-PRESSURE; NEURONS; CAT; DISCHARGE; OUTFLOW; MEDULLA AB 1. Bursts of sympathetic activity in muscle nerves are phase-locked to the cardiac cycle by the sinoaortic baroreflexes. Acoustic arousal from non-rapid eye movement (NREM) sleep reduces the normally invariant interval between the R-wave of the electrocardiogram (ECG) and the peak of the corresponding sympathetic burst; however, the effects of other forms of sleep disruption (i.e. spontaneous arousals and apnoea-induced arousals) on this temporal relationship are unknown. 2. We simultaneously recorded muscle sympathetic nerve activity in the peroneal nerve (intraneural electrodes) and the ECG (surface electrodes) in seven healthy humans and three patients with sleep apnoea syndrome during NREM sleep. 3. In seven subjects, burst latencies were shortened subsequent to spontaneous K complexes (1.297 +/- 0.024 s, mean +/- S.E.M.) and spontaneous arousals (1.268 +/- 0.044 s) compared with latencies during periods of stable NREM sleep (1.369 +/- 0.023 s). In six subjects who demonstrated spontaneous apnoeas during sleep, apnoea per se did not alter burst latency relative to sleep with stable electroencephalogram (EEG) and breathing (1.313 +/- 0.038 vs. 1.342 +/- 0.026 s); however, following apnoea-induced EEG perturbations, burst latencies were reduced (1.214 +/- 0.034 s). 4. Arousal-induced reduction in sympathetic burst latency may reflect a temporary diminution of baroreflex buffering of sympathetic outflow. If so, the magnitude of arterial pressure perturbations during sleep (e.g. those caused by sleep disordered breathing and periodic leg movements) may be augmented by arousal. C1 William S Middleton Mem Vet Hosp, Pulm Physiol Lab, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Dept Surg, Madison, WI 53705 USA. RP Xie, AL (reprint author), William S Middleton Mem Vet Hosp, Pulm Physiol Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. EM axie@facstaff.wisc.edu NR 31 TC 19 Z9 19 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAR 1 PY 1999 VL 515 IS 2 BP 621 EP 628 DI 10.1111/j.1469-7793.1999.621ac.x PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 182VQ UT WOS:000079519200028 PM 10050027 ER PT J AU Gimpelson, RJ Graham, B AF Gimpelson, RJ Graham, B TI Using Amino-Cerv after cervical LEEP SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE cervix neoplasms; Amino-Cerv; loop electrical excision procedure AB OBJECTIVE: To evaluate the ability of Amino-Cerv to promote healing of the cervix following loop electrical excision procedure (LEEP) of the cervix for cervical intraepithelial neoplasia. STUDY DESIGN: A randomized study was conducted on 48 women in a private office setting. Patients were divided into two groups, to use or not use Amino-Cerv intravaginally for two weeks after the procedure. Statistical analysis of the findings were performed using the chi(2) test. RESULTS: Twenty of 24 (83%) of women using Amino-Cerv had completely healed tissue at four weeks, whereas 12 of 24 (50%) in the untreated group had healed tissue at four weeks. Findings we-re not statistically significant at two weeks but were statistically significant (P<.005, power=.55) at four weeks after the procedure. CONCLUSION: Amino-Cerv after LEEP of the cervix promotes healing. C1 St Louis Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO USA. Deaconess Med Ctr W, St Louis, MO USA. RP Gimpelson, RJ (reprint author), St Lukes Hosp, 222 S Woods Mill Rd,Suite 400, Chesterfield, MO 63017 USA. NR 5 TC 4 Z9 7 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAR PY 1999 VL 44 IS 3 BP 275 EP 278 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 183GH UT WOS:000079545500008 PM 10202747 ER PT J AU Merkel, PA Chang, YC Pierangeli, SS Harris, EN Polisson, RP AF Merkel, PA Chang, YC Pierangeli, SS Harris, EN Polisson, RP TI Comparison between the standard anticardiolipin antibody test and a new phospholipid test in patients with connective tissue diseases SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE antiphospholipid antibodies; anticardiolipin antibodies; connective tissue disease; diagnosis ID SYSTEMIC LUPUS-ERYTHEMATOSUS; LARGE INCEPTION COHORT; ANTIPHOSPHOLIPID ANTIBODIES; ANTI-BETA(2)-GLYCOPROTEIN-I ANTIBODIES; SYPHILIS; CARDIOLIPIN; BETA(2)-GLYCOPROTEIN-I; AUTOANTIBODIES; ASSOCIATION; THROMBOSIS AB Objective. Antiphospholipid (aPL) antibodies are present in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibody syndrome (APS) and are associated with recurrent thromboses, thrombocytopenia, and pregnancy losses. The presence of aPL antibodies is routinely tested using a standardized ELISA that utilizes cardiolipin as antigen (aCL ELISA). This test, although sensitive: is frequently positive inpatients with nonrelated autoimmune disorders and some infectious diseases, making the test less specific. Thus there is a need for more specific tests for aCL with equivalent sensitivity to the standard assay. We evaluated the diagnostic utility of a new aPL antibody test kit with a unique phospholipid mixture designed to be more specific than the standard anticardiolipin ELISA. Methods, aPL antibodies (IgG, ISM) were measured by both a standard ELISA and a new ELISA kit (APhL(R) (TM)ELISA Kit, Louisville APL Diagnostics, Inc., Louisville, KY, USA) in the baseline serum from patients enrolled in a 5 year inception cohort, prospective study of early rheumatoid diseases: rheumatoid arthritis (N = 70), SLE (70), scleroderma (45), inflammatory myositis (36), and early undifferentiated connective tissue disease (CTD) (165). Diagnosis was based on standardized criteria and determined at the last study visit. A nested group of patients with Sjogren's syndrome (44) was also defined. Serum from 200 blood donors (BD) served as controls. Patients with known APS (33) and antinuclear cytoplasmic antibody positive renal vasculitis (52) were also studied. Laboratory personnel were blinded to sample diagnostic group. Results, The kit was 90.9% sensitive for detecting APS. Seven patients missed by the kit all had standard aCL values < 40 PL units. Assuming controls do not have APS, the kit was 99.5% specific vs 96.0% for the standard assay. For the patients with CTD, the kit never detected a patient that was not also detected by the standard aCL assay. Conclusion. The APhL (TM)ELISA Kit appears to be more specific than the standard aCL ELISA without adding potential false positive results. The new test may be useful for followup study for patients found to be aCL positive by standard assays to increase specificity for aCL screening. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Arthrit Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practice Evaluat Ctr, Boston, MA USA. Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA. Morehouse Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30310 USA. RP Merkel, PA (reprint author), Boston Univ, Sch Med, Ctr Arthritis, K-5,715 Albany St, Boston, MA 02118 USA. FU NCRR NIH HHS [M01 RR01066, RR03034] NR 30 TC 36 Z9 39 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 1999 VL 26 IS 3 BP 591 EP 596 PG 6 WC Rheumatology SC Rheumatology GA 173DX UT WOS:000078966900015 PM 10090168 ER PT J AU Warner, JJP Ejnisman, B Akpinar, S AF Warner, JJP Ejnisman, B Akpinar, S TI Surgical management of heterotopic ossification of the shoulder SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article C1 Univ Pittsburgh, Ctr Sports Med, Dept Orthopaed Surg, Shoulder Serv, Pittsburgh, PA USA. Univ Istanbul, Sch Med, Dept Orthopaed Surg, Istanbul, Turkey. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,Suite 403, Boston, MA 02114 USA. NR 14 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAR-APR PY 1999 VL 8 IS 2 BP 175 EP 178 DI 10.1016/S1058-2746(99)90015-0 PG 4 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 188FM UT WOS:000079836200016 PM 10226974 ER PT J AU Mulvaney, FD Alterman, AI Boardman, CR Kampman, K AF Mulvaney, FD Alterman, AI Boardman, CR Kampman, K TI Cocaine abstinence symptomatology and treatment attrition SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE cocaine; treatment attrition; CSSA; logistic regression ID ABUSE TREATMENT; PSYCHOTHERAPY; RETENTION; DEPENDENCE AB Premature termination from outpatient cocaine treatment predicts a number of poor outcomes, including higher rates of relapse and unemployment This study attempted to predict dropouts from outpatient cocaine treatment, as well as those unable to achieve initial abstinence from cocaine, using two baseline variables that had previously been shown to predict treatment dropout: a measure of the severity of cocaine abstinence symptomatology using the Cocaine Selective Severity Assessment (CSSA) and the initial urine toxicology. Results of logistic regression analyses indicated that those with more intense abstinence symptoms, as measured by the CSSA, were five times more likely to terminate treatment prematurely. when combined with the CSSA, the initial urine did not significantly predict dropouts. The CSSA and the baseline urine were equal in their ability to predict those who would fail in their initial attempts to achieve abstinence. Implications for treatment are discussed. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Univ Penn, Subst Abuse Unit, Vet Affairs Med Ctr, Sch Med, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Mulvaney, FD (reprint author), Univ Penn, Subst Abuse Unit, Vet Affairs Med Ctr, Sch Med, Bldg 7,Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA05186] NR 19 TC 57 Z9 58 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR PY 1999 VL 16 IS 2 BP 129 EP 135 DI 10.1016/S0740-5472(98)00017-8 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 162UH UT WOS:000078364800004 PM 10023610 ER PT J AU Oslin, DW Pettinati, HM Volpicelli, JR Wolf, AL Kampman, KM O'Brien, CP AF Oslin, DW Pettinati, HM Volpicelli, JR Wolf, AL Kampman, KM O'Brien, CP TI The effects of naltrexone on alcohol and cocaine use in dually addicted patients SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article; Proceedings Paper CT Annual Meeting of the Research-Society-of-Alcoholism CY JUL, 1997 CL SAN FRANCISCO, CALIFORNIA SP Res Soc Alcoholism DE alcoholism; cocaine dependence; naltrexone; treatment ID DEPENDENCE; ABUSE; DISORDERS AB Concurrent dependence on cocaine and alcohol is common among patients seeking addiction treatment. This study was undertaken to explore the effectiveness of naltrexone (150 mg) as a potential treatment for patients who are alcohol and cocaine dependent. Of 15 subjects enrolled in the 12-week, open medication trial, 7 subjects did riot complete the study. Relapse to clinically significant drinking occurred in 7 subjects (47%). There was a reduction in the average daily amount of alcohol consumed from pretreatment to treatment (p <.001) and the percentage of days engaged in drinking behavior (p <.001). Similarly: there was a reduction in the average weekly amount spent on cocaine from pretreatment to treatment (p =.001) mid the percentage of days using cocaine (p <.001). This preliminary study suggests that naltrexone (150 mg) may be tolerable in patients dependent upon alcohol and cocaine and may be effective in reducing both cocaine and alcohol use. The results of this study provide a rationale for a double-blind placebo-controlled study of the efficacy of naltrexone in this difficult to treat but prevalent population. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Univ Penn, Ctr Study Addict, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Oslin, DW (reprint author), Univ Penn, Addict Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM oslin@mail.med.upenn.edu FU PHS HHS [P60] NR 18 TC 44 Z9 44 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR PY 1999 VL 16 IS 2 BP 163 EP 167 DI 10.1016/S0740-5472(98)00039-7 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 162UH UT WOS:000078364800009 PM 10023615 ER PT J AU Jellinek, MS AF Jellinek, MS TI A clinical trial for adolescent depression: Predictors of additional treatment in the acute and follow-up phases of the trial - Commentary SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Psychiat, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jellinek, MS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Child Psychiat Serv, 55 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1999 VL 38 IS 3 BP 270 EP 271 DI 10.1097/00004583-199903000-00013 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 170XJ UT WOS:000078832100014 ER PT J AU Bostic, JQ Rauch, PK AF Bostic, JQ Rauch, PK TI The 3 r's of school consultation SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Massachusetts Gen Hosp, Sch Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Bostic, JQ (reprint author), Massachusetts Gen Hosp, Sch Psychiat, 15 Parkman St,WAC 725, Boston, MA 02114 USA. NR 8 TC 6 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1999 VL 38 IS 3 BP 339 EP 341 DI 10.1097/00004583-199903000-00023 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 170XJ UT WOS:000078832100024 PM 10087697 ER PT J AU Khan, IU Bhol, KC Ahmed, AR AF Khan, IU Bhol, KC Ahmed, AR TI Linear IgA bullous dermatosis in a patient with chronic renal failure: Response to intravenous immunoglobulin therapy SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID INDIRECT IMMUNOFLUORESCENCE; PEMPHIGUS-VULGARIS; BASEMENT-MEMBRANE; AUTOANTIBODIES; DISEASE AB Linear IgA bullous dermatosis is a blistering disease with a heterogeneous clinical manifestation, characterized by deposition of IgA along the basement membrane zone of perilesional skin on direct immunofluorescence. We describe a patient with chronic renal failure who experienced linear IgA bullous dermatosis. Long-term administration of intravenous immunoglobulin therapy was associated with clinical remission lasting more than 12 months. C1 Harvard Univ, Sch Med, Ctr Blood Res, New England Baptist Hosp,Dept Med, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NEI NIH HHS [EY08379] NR 21 TC 41 Z9 44 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 1999 VL 40 IS 3 BP 485 EP 488 DI 10.1016/S0190-9622(99)70504-9 PG 4 WC Dermatology SC Dermatology GA 171MH UT WOS:000078867300017 PM 10071325 ER PT J AU Lehmann, KG Platt, MS AF Lehmann, KG Platt, MS TI Improved accuracy and precision of thermodilution cardiac output measurement using a dual thermistor catheter system SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 70th Scientific Session of the American-Heart-Association Meeting CY NOV 09-13, 1997 CL ORLANDO, FLORIDA SP Amer Heart Assoc ID THERMAL DILUTION; REPRODUCIBILITY; TEMPERATURE AB OBJECTIVES To assess whether thermodilution cardiac output determination based on measurement of injectate temperature in vivo leads to more accurate and precise estimates and to study the influence of chilled injectate on test performance. BACKGROUND Cardiac output measurement via right heart catheterization is used extensively for hemodynamic evaluation in a variety of diagnostic, perioperative and critical care settings. Maximizing accuracy is essential for optimal patient care. METHODS This prospective study of 960 thermodilution cardiac output measurements was conducted using conventional and dual thermistor techniques. Specialized dual thermistor right heart catheters were constructed using a second thermistor positioned to measure injectate temperature in vivo just prior to entry into the right atrium. To eliminate interinjection variability, a custom set-up was developed that permitted output measurement using both techniques simultaneously. Both ambient temperature injections and cooled injections were investigated. RESULTS The dual thermistor technique demonstrated significantly less measurement Variability than the conventional technique for both ambient temperature (precision = 0.41 vs. 0.55 L/min, p < 0.001) and cooled (precision = 0.35 vs. 0.43 L/min, p = 0.01) injections. Similarly, the average range of cardiac output values obtained during five sequential injections in each patient was less using the dual thermistor approach (1.05 vs. 1.55 L/min, p < 0.001). The use of cooled injectate reduced the mean error of the dual thermistor technique but actually increased the mean error of the conventional technique. Even with ambient temperature injections, injectate warming during; catheter transit varied considerably and unpredictably from injection to injection (2 SD range = -0.22 to 5.74 degrees C). Conventional ambient temperature and cooled measurements significantly overestimated Fick cardiac output measurements by 0.32 and 0.50 L/min, respectively (p < 0.001). In contrast, dual thermistor measurements were statistically similar (-0.08 and -0.08 L/min, p = 0.34) to Fick measurements. CONCLUSIONS This new dual thermistor approach results in a significant improvement in both precision and accuracy of thermodilution cardiac output measurement. (C) 1999 by the American College of Cardiology. C1 VA Puget Sound Hlth Care Syst, Sect Cardiol 111C, Seattle, WA 98108 USA. Univ Washington, Sch Med, Cardiol Sect, Seattle, WA USA. RP Lehmann, KG (reprint author), VA Puget Sound Hlth Care Syst, Sect Cardiol 111C, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 23 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 1999 VL 33 IS 3 BP 883 EP 891 DI 10.1016/S0735-1097(98)00639-1 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176YF UT WOS:000079179400039 PM 10080494 ER PT J AU Hansen, K Mahoney, J Palta, M AF Hansen, K Mahoney, J Palta, M TI Risk factors for lack of recovery of ADL independence after hospital discharge SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT 50th Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 07-18, 1997 CL CINCINNATI, OHIO SP Gerontol Soc Amer DE recovery; ADLs; independence ID ACUTE MEDICAL ILLNESS; MINI-MENTAL-STATE; FUNCTIONAL STATUS; ELDERLY PERSONS; OLDER PATIENTS; NURSING-HOME; SELF-REPORT; PERFORMANCE; PEOPLE; DEPRESSION AB OBJECTIVE: To determine risk factors for lack of recovery of independent functioning after hospitalization fur acute medical illness. DESIGN: Secondary analysis of cohort study of patients receiving home nursing after discharge. SETTING: Evaluations performed in the home after discharge and 1 month later. PARTICIPANTS: A total of 73 adults aged 65 years and older who were independent in activities of daily living (ADLs) before hospitalization and dependent at discharge. MEASUREMENTS: Self-report and objective measures of function, mobility, and cognition. OUTCOME: Return to independence in ADLs 1 month after discharge. RESULTS: Fifty-nine percent of patients did nor; return to previous ADL independence by 1 month postdischarge. The likelihood for not recovering was 87% (95% CI, 70-100%) if a patient had a Mini-Mental State Examination score (MMSE) < 24 at discharge (P = .015), Among patients with good cognition, 85% (95% CI, 66-100%) of those who used an assistive device indoors before hospitalization did not recover (P = .007), Among patients with good cognition and no previous assistive device use, 73% (95% CI, 47-99%) of those with a Timed "Up and Go" of greater than or equal to 40 seconds did not recover (P = .012). The likelihood of recovery was high (76%, 95% CI 56-96%) if a patient had no assistive device prehospital, a good MMSE, and, a Timed "Up and Go" of < 20 seconds. CONCLUSION: We hypothesize that a classification strategy using cognition, prehospital mobility, and discharge physical performance will predict patients who are less likely to recover functional independence after hospitalization. If this is validated in future study, it may help clinicians identify patients who are more likely to benefit from additional intervention. C1 William S Middleton Mem Vet Hosp, GRECC Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. Univ Wisconsin, Sch Med, Dept Prevent Med, Madison, WI USA. RP Mahoney, J (reprint author), William S Middleton Mem Vet Hosp, GRECC Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NIA NIH HHS [K08AG00623] NR 35 TC 49 Z9 49 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 1999 VL 47 IS 3 BP 360 EP 365 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 173BR UT WOS:000078961500015 PM 10078901 ER PT J AU Hunziker, PR Picard, MH Jander, N Scherrer-Crosbie, M Pfisterer, M Buser, PT AF Hunziker, PR Picard, MH Jander, N Scherrer-Crosbie, M Pfisterer, M Buser, PT TI Regional wall motion assessment in stress echocardiography by tissue Doppler bull's-eyes SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article AB Quantification of regional myocardial wall velocities is needed In stress echocardiography for transition from subjective to quantitative assessment. Tissue Doppler allows quantitation of wall velocities, but interpretation is difficult and angle-dependent, Calculating the ratios of velocities with similar angles to the beam map overcome angle dependency. We measured left ventricular wall velocities during stress echocardiography with tissue Doppler. Regional peak systolic and early (E) and late (A) diastolic velocities were constructed in a "bull's-eye" format. Regional stress/rest and E/A ratios were calculated. Bull's-eye map construction demanded only minimal manual interaction, and the maps showed the left ventricular velocity distribution, simplifying wall motion reading markedly. Still, apical velocities appeared lower as a result of Doppler angle-dependency. With velocity ratios, angle-dependency was no longer noted. In stress echocardiography, wall motion abnormalities at rest and contractility changes with dobutamine became readily apparent. Bull's-eye display of quantitative tissue Doppler velocity allows rapid. assessment of regional wall motion. Calculating the ratio of regional velocities circumvents the angle-dependency of Doppler. This novel technique has the potential for simplified and automated quantitative analysis in stress echocardiography. C1 Univ Basel Hosp, Div Cardiol, CH-4031 Basel, Switzerland. Massachusetts Gen Hosp, Cardiac Ultrasound Unit, Boston, MA 02114 USA. RP Hunziker, PR (reprint author), Univ Basel Hosp, Div Cardiol, Petersgraben 4, CH-4031 Basel, Switzerland. OI Picard, Michael/0000-0002-9264-3243 NR 11 TC 23 Z9 25 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAR PY 1999 VL 12 IS 3 BP 196 EP 202 DI 10.1016/S0894-7317(99)70135-5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 174NK UT WOS:000079041100006 PM 10070183 ER PT J AU Anger, WK Storzbach, D Binder, LM Campbell, KA Rohlman, DS McCauley, L Kovera, CA Davis, KL AF Anger, WK Storzbach, D Binder, LM Campbell, KA Rohlman, DS McCauley, L Kovera, CA Davis, KL CA Portland Env Hazards Res Ctr TI Neurobehavioral deficits in Persian Gulf veterans: Evidence from a population-based study SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE neurobehavioral assessment; Persian Gulf War; PGW ID CHRONIC NEUROLOGICAL SEQUELAE; WAR VETERANS; HEALTH; QUESTIONNAIRES; INSTRUCTIONS; VALIDATION; SELECTION; SCALE AB Reports of low-concentration nerve gas exposures during the Persian Gulf War have spurred concern about possible health consequences and refocused interest on the symptoms reported by many returning military veterans. The Portland Environmental Hazards Research Center is studying veterans from the Northwest USA who report persistent, unexplained "Persian Gulf" symptoms (cases) or who do not report those symptoms (controls). Of the first 101 veterans studied, cases differed substantially from controls on a broad range of psychological tests indicative of increased distress. A subgroup of cases was identified with objective deficits on neurobehavioral tests of memory, attention, and response speed. C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97207 USA. RP Anger, WK (reprint author), Oregon Hlth Sci Univ, CROET L606,3181 SW Sam Jackson Rd, Portland, OR 97201 USA. EM anger@ohsu.edu RI Rohlman, Diane/E-5556-2015 OI Rohlman, Diane/0000-0002-6697-1577 NR 53 TC 35 Z9 36 U1 1 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAR PY 1999 VL 5 IS 3 BP 203 EP 212 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 184BD UT WOS:000079588700003 PM 10217920 ER PT J AU Blacconiere, MJ Oleckno, WA AF Blacconiere, MJ Oleckno, WA TI Health-promoting behaviours in public health: testing the Health Promotion Model SO JOURNAL OF THE ROYAL SOCIETY FOR THE PROMOTION OF HEALTH LA English DT Article DE health promotion; health behaviour; lifestyle; public health; wellness ID PHYSICAL-ACTIVITY; DETERMINANTS; NURSES AB A health-promoting lifestyle encompasses far more than preventing disease and is characterised by behaviours that lead to optimal well-being, self-actualisation, and personal fulfillment. This study was undertaken to investigate the health-promoting lifestyles of employees working in local public health departments (n=602) and to test two research hypotheses suggested by the Health Promotion Model. The first hypothesis posited that public health professionals would report significantly more favourable health-promoting behaviours than support staff employed in the same departments. The second hypothesis postulated that occupational discipline in public health would be a significant predictor of health-promodng behaviours. Health-promoting behaviours were measured by the Health-Promoting Lifestyle Profile (HPLP), a psychometrically-validated measure of overall health-promoting lifestyle and six dimensions of health-promoting behaviours, which comprise the instrument's subscales. The findings of the study tended to support the research hypotheses. Overall, public health professionals tended to report more favourable health-promoting behaviours than departmental support staff, and occupational discipline was a significant predictor of a health-promoting lifestyle. In general, public health nursing personnel reported the highest mean levels of health-promoting behaviours compared to the other occupational disciplines examined. C1 No Illinois Univ, Sch Allied Hlth Profess, Publ Hlth Program, De Kalb, IL 60115 USA. No Illinois Univ, Sch Allied Hlth Profess, Community Hlth Program, De Kalb, IL 60115 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Dominican Univ, River Forest, IL 60305 USA. RP Oleckno, WA (reprint author), No Illinois Univ, Sch Allied Hlth Profess, Publ Hlth Program, De Kalb, IL 60115 USA. NR 23 TC 3 Z9 3 U1 2 U2 5 PU ROYAL SOC OF HEALTH PI LONDON PA 38A ST, GEORGES DR, LONDON SW1V 4BH, ENGLAND SN 1466-4240 J9 J R SOC PROMO HEALTH JI J. R. Soc. Promot. Health PD MAR PY 1999 VL 119 IS 1 BP 11 EP 16 DI 10.1177/146642409911900103 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 255XZ UT WOS:000083696600009 PM 10327809 ER PT J AU Potter, DA Luther, MF Eddy, CA Siler-Khodr, TM King, TS Schenken, RS AF Potter, DA Luther, MF Eddy, CA Siler-Khodr, TM King, TS Schenken, RS TI Low-dose follicular-phase cocaine administration disrupts menstrual and ovarian cyclicity in rhesus monkeys SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 19-23, 1996 CL PHILADELPHIA, PENNSYLVANIA SP Soc Gynecol Invest, NIH DE cocaine; low dose; follicular phase; menstrual cyclicity ID PROGESTERONE; INDUCTION; ESTROGEN; CYCLES; WOMEN AB OBJECTIVE: To evaluate the effects of daily low-dose follicular-phase cocaine administration on menstrual cyclicity, ovulation rates, corpus luteum function, and hormone levels in rhesus monkeys. METHODS: Normally cycling, drug-naive, adult rhesus monkeys were randomized to receive either 1 mg/kg of cocaine (n = 7), 2 mg/kg of cocaine (n = 7), or normal saline (n = 7) daily on cycle days 2 to 14. Daily blood samples were obtained through indwelling catheters for measurement of serum gonadotropins and ovarian steroids. Daily vaginal swabs were obtained to determine onset of menses. Laparoscopy was performed 2 days after the midcycle estrogen peak to document ovulation. Daily caloric intakes as well as pretreatment and posttreatment weights were recorded. RESULTS: Two of seven monkeys receiving 1 mg/kg per day and two of seven monkeys receiving 2 mg/kg per day of cocaine had timely ovulation and normal menstrual cycle lengths. One monkey receiving the 2-mg/kg dose ovulated on cycle day 24 and had a short luteal phase (7 days) with a mean progesterone level of 2.4 ng/mL. All seven saline-treated control monkeys ovulated normally; the mean cycle length was 29 days and all had adequate luteal phases. The difference in ovulation rates between cocaine-treated and control monkeys was statistically significant (P = .003). There were no differences in basal levels of LH or FSH between treatment groups. There were no significant differences in weight change or caloric intake among groups. One third of the subsequent menstrual cycles in cocaine-treated monkeys were of abnormal duration. CONCLUSION: Daily lo-dose follicular-phase cocaine administration disrupts menstrual cyclicity and folliculogenesis. This effect is independent of weight loss, caloric intake, and basal gonadotropin levels. Cocaine exposure may have a persistent effect on menstrual and ovarian cyclicity in some monkeys. Copyright (C) 1999 by the Society for Gynecologic Investigation. C1 Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Dept Res & Dev, San Antonio, TX 78284 USA. RP Schenken, RS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM schenken@uthscsa.edu FU NIDA NIH HHS [DA08295] NR 24 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD MAR-APR PY 1999 VL 6 IS 2 BP 88 EP 94 DI 10.1016/S1071-5576(98)00054-9 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 183FQ UT WOS:000079543900007 PM 10205779 ER PT J AU Schoenike, B Franta, AK Fleming, JO AF Schoenike, B Franta, AK Fleming, JO TI Quantitative sense-specific determination of murine coronavirus RNA by reverse transcription polymerase chain reaction SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE PCR; sense-specific RNA determination; mouse hepatitis virus; coronaviruses ID C VIRUS-RNA; MESSENGER-RNA; RT-PCR; OVERLAP EXTENSION; HEPATITIS; STORAGE; INFECTION; VARIANTS; IMPACT; GENE AB In many applications, it is useful to know the sense and amount of viral RNAs present in a sample. In theory, sense-specific measurement of viral RNAs may be achieved by reverse transcription polymerase chain reaction (RT-PCR) assays which utilize primers of defined polarity during the RT step. However, in practice, it has been shown that such assays are prone to artifacts, such as non-specific priming, which drastically diminish their reliability Using murine coronavirus MHV-4 as a model, we describe and validate several modifications of the RT-PCR procedure which eliminate these artifacts. Key RT-PCR parameters which were optimized include the design of tagged primers, DNase treatment of in vitro transcribed RNA standards, specification of temperature differences between RT and PCR annealing steps, and use of competitive RNA templates for quantitative assays. The assays described may be used to determine the sense and abundance of any viral or host RNA of interest in complex biological specimens. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Wisconsin, Dept Neurol, Madison, WI 53906 USA. Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. William S Middleton Mem Vet Hosp, Madison, WI 53792 USA. RP Fleming, JO (reprint author), Univ Wisconsin, Dept Neurol, 1300 Univ Ave, Madison, WI 53906 USA. NR 36 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAR PY 1999 VL 78 IS 1-2 BP 35 EP 49 DI 10.1016/S0166-0934(98)00167-0 PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 179HA UT WOS:000079319400004 PM 10204695 ER PT J AU Mariani, R Wong, S Mulder, LCF Wilkinson, DA Reinhart, AL LaRosa, G Nibbs, R O'Brien, TR Michael, NL Connor, RI Macdonald, M Busch, M Koup, RA Landau, NR AF Mariani, R Wong, S Mulder, LCF Wilkinson, DA Reinhart, AL LaRosa, G Nibbs, R O'Brien, TR Michael, NL Connor, RI Macdonald, M Busch, M Koup, RA Landau, NR TI CCR2-64I polymorphism is not associated with altered CCR5 expression or coreceptor function SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM SURVIVOR; CHEMOKINE RECEPTOR GENE; VIRUS TYPE-1 INFECTION; HIV-1 INFECTION; DISEASE PROGRESSION; DELETION ALLELE; INDIVIDUALS; RESISTANCE; TRANSMISSION; NEF AB A polymorphism in the gene encoding CCR2 is associated with a delay in progression to AIDS in human immunodeficiency virus (HIV)-infected individuals. The polymorphism, CCR2-64I, changes valine 64 of CCR2 to isoleucine. However, it is not clear whether the effect on AIDS progression results from the amino acid change or whether the polymorphism marks a genetically linked, yet unidentified mutation that mediates the effect. Because the gene encoding CCR5, the major coreceptor for HIV type 1 primary isolates, ties, 15 kb 3' to CCR2, linked mutations in the CCR5 promoter or other regulatory sequences could explain the association of CCR2-64I with slowed AIDS pathogenesis. Here, we show that CCR2-64I is efficiently expressed on the cell surface but does not have dominant negative activity on CCR5 coreceptor function. A panel of peripheral blood mononuclear cells (PBMC) from uninfected donors representing the various CCR5/CCR2 genotypes was assembled. Activated primary CD4(+) T cells of CCR2 64I/64I donors expressed cell surface CCR5 at levels comparable to those of CCR2 +/+ donors. A slight reduction in CCR5 expression was noted, although this was not statistically significant. CCR5 and CCR2 mRNA levels were nearly identical for each of the donor PBMC, regardless of genotype. Cell surface CCR5 and CCR2 levels were more variable than mRNA transcript levels, suggesting that an alternative mechanism may influence CCR5 cell surface levels. CCR2-64I is linked to the CCR5 promoter polymorphisms 208G, 303A, 627C, and 676A; however, in transfected promoter reporter constructs, these did not affect transcriptional activity. Taken together, these findings suggest that CCR2-64I does not act by influencing CCR5 transcription of mRNA levels. C1 Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Univ Texas, SW Med Ctr, Div Infect Dis, Dallas, TX 75235 USA. Leukosite Inc, Cambridge, MA 02142 USA. Beatson Inst Canc Res Campaign, Glasgow G61 1BD, Lanark, Scotland. NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Irwin Mem Blood Ctr, San Francisco, CA 94118 USA. RP Landau, NR (reprint author), Salk Inst Biol Studies, Infect Dis Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM landau@salk.edu FU NCI NIH HHS [R01 CA72149, R01 CA43252]; NIAID NIH HHS [R01 AI072149, R29 AI36057] NR 53 TC 50 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 2450 EP 2459 PG 10 WC Virology SC Virology GA 166XT UT WOS:000078603800080 PM 9971830 ER PT J AU Cookman, S Verdolini, K AF Cookman, S Verdolini, K TI Interrelation of mandibular laryngeal functions SO JOURNAL OF VOICE LA English DT Article DE jaw; larynx; EGG; bite-block ID SPEAKING FUNDAMENTAL-FREQUENCY; MUSCLE SPINDLE AFFERENTS; VOCAL FOLD CONTACT; INTRACELLULAR BIOTINAMIDE; BRAIN-STEM; PATTERNS; NEURONS; NUCLEUS; RAT; ELECTROGLOTTOGRAM AB The purpose of the experiment was to explore relations between jaw and laryngeal functions. The general question was whether laryngeal adduction was affected by jaw opening or by jaw biting. Twelve untrained, vocally healthy male and female adults participated as subjects. Subjects produced repeated tokens of /Lambda / in each of 12 experimental conditions involving combinations of 3 jaw openings (10 mm, 25 mm, 40 mm), 2 jaw biting pressures (10 kPa, 200 kPa), and 2 fundamental frequencies (conversational and high). For each token, laryngeal adduction was estimated from the electroglottographic closed quotient. The most straightforward results were that (1) laryngeal adduction increased as jaw opening increased at the conversational pitch, for all subjects, independent of biting pressure, and (2) laryngeal adduction increased as biting pressure increased, at the conversational pitch, for males, independent of jaw opening. Other relations between estimated laryngeal adduction and jaw manipulations were more complex, varying with fundamental frequency and gender. Speculations are made about possible biomechanical and neurological explanations for the findings. C1 Univ Connecticut, Ctr Hlth, Dept Speech Pathol & Audiol, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Natl Ctr Voice & Speech, Farmington, CT 06030 USA. Harvard Univ, Brigham & Womens Hosp,Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr,Inst Hlth Profess, Joint Ctr Otolaryngol,Sch Med,Voice Speech Swallo, Boston, MA 02115 USA. RP Cookman, S (reprint author), Univ Connecticut, Ctr Hlth, CCC, SLP,Voice & Speech Clin, MC-3955 Farmington Ave, Farmington, CT 06030 USA. NR 43 TC 16 Z9 19 U1 0 U2 0 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 0892-1997 J9 J VOICE JI J. Voice PD MAR PY 1999 VL 13 IS 1 BP 11 EP 24 DI 10.1016/S0892-1997(99)80057-5 PG 14 WC Otorhinolaryngology SC Otorhinolaryngology GA 278RN UT WOS:000085002900002 PM 10223671 ER PT J AU Zeitels, SM Sataloff, RT AF Zeitels, SM Sataloff, RT TI Phonomicrosurgical resection of glottal papillomatosis SO JOURNAL OF VOICE LA English DT Article DE laryngeal papillomatosis; papilloma; microflap; phonosurgery; phonomicrosurgery; dysphonia; laryngoscopy; microlaryngoscopy; vocal fold; vocal cord ID CLINICAL EXPERIENCE; LASER SURGERY; CO2-LASER; LARYNX AB Controlled debulking has been the surgical approach to treat laryngeal papillomatosis for over a century despite dramatic improvements in surgical technology. It is commonplace to leave disease: in the glottis at the end of the procedure (eg, in the anterior commissure) because of complications associated with attempted complete removal. This study examined the recurrence patterns of adult glottal papillomatosis after phonomicrosurgical microflap resection. Between 1990 and 1995, 22 patients underwent phonomicrosurgical resection of glottal papillomatosis. Six patients had not undergone previous microlaryngeal surgery and 16 patients had had prior procedures. All patients underwent resection of all visible papillomatosis, and this frequently required staged resections. The subepithelial infusion technique was used to facilitate the resection in most cases. No patient who underwent resection for primary disease had a recurrence. Ten of 16 (62%) patients who presented with recurrent disease did not have a recurrence after microflap resection. Follow up on all patients was at least 2 years. This preliminary report suggests that recently developed phonomicrosurgical microflap resection techniques can eradicate adult glottal papillomatosis in some cases, and that resection of papillomatosis appears to be preferable to conventional debulking and/or ablation techniques. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Grad Hosp Philadelphia, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA 19146 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 26 TC 13 Z9 13 U1 0 U2 2 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 0892-1997 J9 J VOICE JI J. Voice PD MAR PY 1999 VL 13 IS 1 BP 123 EP 127 DI 10.1016/S0892-1997(99)80066-6 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 278RN UT WOS:000085002900011 PM 10223680 ER PT J AU Prinz, PN Scanlan, JM Vitaliano, PP Moe, KE Borson, S Toivola, B Merriam, GR Larsen, LH Reed, HL AF Prinz, PN Scanlan, JM Vitaliano, PP Moe, KE Borson, S Toivola, B Merriam, GR Larsen, LH Reed, HL TI Thyroid hormones: Positive relationships with cognition in healthy, euthyroid older men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID SUBCLINICAL HYPOTHYROIDISM; THYROTROPIN; RESPONSES; INDEXES; SCALE AB Background. Although the association of clinical hypothyroidism with cognitive deficits is well known, the cognitive effects of thyroid hormones in euthyroid subjects are less studied and understood. The purpose of this study was to examine thyroid-cognition relationships in healthy, euthyroid older men. Methods. We examined healthy men (N = 44, mean age = 72), excluding clinically hypothyroid/hyperthyroid or diabetic/hyperglycemic subjects and those with dementia, depression, CNS medications, or recent illness. Plasma samples obtained across a 24-hour period were pooled, then assayed for total thyroxine (TT4), total triiodothyronine (TT3), and T3 resin uptake. Free thyroxine index (FT4I) was calculated. A broad cognitive battery (including the Wechsler Adult Intelligence Scale-Revised [WAIS-R], the Dementia Rating Scale [DRS], and the Rivermead Behavioral Profile [PROFILE]) was administered to all subjects. Results. Regression analyses controlling age and education showed TT4 and FT4I to have significant positive relationships with measures of overall cognition; TT4 accounted for 8% to 12% of the variance in omnibus cognitive measures such as WAIS Performance, WAIS Verbal score, and GLOBAL cognitive scores. Conclusions. Our findings suggest that within "normal" range of variation in plasma thyroid hormones, TT4 but not T3 positively associates with general cognition in healthy elderly men. C1 Univ Washington, Dept Psychiat & Biobehav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biobehav Nursing, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, Tacoma, WA USA. Madigan Army Med Ctr, Tacoma, WA 98431 USA. RP Prinz, PN (reprint author), Univ Washington, Dept Biobehav Nursing & Hlth Syst, Box 357266, Seattle, WA 98195 USA. FU NCRR NIH HHS [RR37]; NIMH NIH HHS [MH33688, MH52126] NR 38 TC 34 Z9 36 U1 0 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 1999 VL 54 IS 3 BP M111 EP M116 DI 10.1093/gerona/54.3.M111 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 179FM UT WOS:000079315200011 PM 10191837 ER PT J AU Moller, MB Ino, Y Gerdes, AM Skjodt, K Louis, DN Pedersen, NT AF Moller, MB Ino, Y Gerdes, AM Skjodt, K Louis, DN Pedersen, NT TI Aberrations of the p53 pathway components p53, MDM2 and CDKN2A appear independent in diffuse large B cell lymphoma SO LEUKEMIA LA English DT Article DE diffuse large B cell non-Hodgkin's lymphoma; p53; p16; p19(ARF); p15; MDM2 ID NON-HODGKINS-LYMPHOMAS; CYCLIN-DEPENDENT KINASE-4; WILD-TYPE; HEMATOLOGICAL MALIGNANCIES; LYMPHOCYTIC-LEUKEMIA; ONCOGENE EXPRESSION; PROTEIN P19(ARF); GENE DELETIONS; P16(INK4A); MUTATIONS AB The two gene products of the CDKN2A gene, p16 and p19(ARF), have recently been linked to each of two major tumour suppressor pathways in human carcinogenesis, the RB1 pathway and the p53 pathway. p16 inhibits the phosphorylation of the retinoblastoma gene product by cyclin D-dependent kinases, whereas p19(ARF) targets MDM2, a p53 inhibitory protein, for degradation. A deletion of CDKN2A would therefore disturb both pathways. To explore the p53 pathway genes as a functional unit in diffuse large B cell non-Hodgkin's lymphomas (DLCL), we wanted to see whether there exists mutually exclusiveness of aberrations of CDKN2A, MDM2 and p53, since this has not been analysed previously. We investigated 37 DLCL for aberrations of p15, p16, p19(ARF), MDM2, and p53 at the epigenetic, genetic and/or protein levers. Homozygous deletion of CDKN2A was detected in seven (19%) of 37 tumours, and another three cases were hypermethylated at the 5' CpG island of p16. No point mutations were found in CDKN2B or CDKN2A. immunohistochemical staining of formalin-fixed, paraffin-embedded tissue for p16 confirmed these results, as all tumours with alterations of CDKN2A were pie immunonegative. We found p53 mutations in eight (22%) cases and MDM2 overexpression in 16 (43%) tumours. Twenty-three (62%) tumours had alterations of one or more p53 pathway components (p53, p19(ARF) and MDM2). Furthermore, 7/9 (78%) p16-immunonegative tumours showed co-aberration of p53 and/or MDM2. The lack of correlation between these aberrations suggests that DLCL acquire additional growth advantage by inactivating both of these critical regulatory pathways. C1 Odense Univ, Dept Pathol, DK-5000 Odense C, Denmark. Odense Univ, Dept Clin Genet, DK-5000 Odense, Denmark. Odense Univ, Dept Med Microbiol, DK-5000 Odense C, Denmark. Massachusetts Gen Hosp, Dept Pathol Neuropathol, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Moller, MB (reprint author), Odense Univ, Dept Pathol, Winslowparken 15, DK-5000 Odense C, Denmark. RI Moller, Michael/G-8340-2016 OI Moller, Michael/0000-0003-2041-3630 NR 50 TC 65 Z9 66 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 1999 VL 13 IS 3 BP 453 EP 459 DI 10.1038/sj.leu.2401315 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 175GX UT WOS:000079086000017 PM 10086736 ER PT J AU Poncelet, BP Koelling, TM Schmidt, CJ Kwong, KK Reese, TG Ledden, P Kantor, HL Brady, TJ Weisskoff, RM AF Poncelet, BP Koelling, TM Schmidt, CJ Kwong, KK Reese, TG Ledden, P Kantor, HL Brady, TJ Weisskoff, RM TI Measurement of human myocardial perfusion by double-gated flow alternating inversion recovery EPI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE heart; myocardial perfusion; arterial spin labeling; echoplanar imaging (EPI); human; swine ID CORONARY MR-ANGIOGRAPHY; BLOOD-FLOW; MAGNETIC-RESONANCE; ARTERIAL WATER; SPIN INVERSION; RELAXATION-TIMES; GD-DTPA; 1.5 T; HEART; QUANTIFICATION AB This paper presents a flow-sensitive alternating inversion recovery (FAIR) method for measuring human myocardial perfusion at 1.5 T. Slice-selectivelnon-selecfive IR images were collected using a double-gated IR echoplanar imaging sequence. Myocardial perfusion was calculated after T1 fitting and extrapolation of the mean signal difference SISel - SINSel. The accuracy of the method was tested in a porcine model using graded intravenous adenosine dose challenge. Comparison with radiolabeled microsphere measurements showed a good correlation (r = 0.84; mean error = 20%, n = 6) over the range of flows tested (0.9-7 ml/g/min). Applied in humans, this method allowed for the measurement of resting myocardial flow (1.04 +/- 0.37 ml/g/min, n = 11). The noise in our human measurements (SEflow = 0.2 ml/g/min) appears to come primarily from residual respiratory motion. Although the current signal-to-noise ratio limits our ability to measure small fluctuations in resting flow accurately the results indicate that this noninvasive method has great promise for the quantitative assessment of myocardial flow reserve in humans. Magn Reson Med 41:510-519, 1999. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Poncelet, BP (reprint author), Massachusetts Gen Hosp, NMR Ctr, CNY-2,Bldg 149,13th St, Charlestown, MA 02129 USA. EM brigitte@nmr.mgh.harvard.edu FU NCI NIH HHS [P01-CA48729, R01-CA66072]; NHLBI NIH HHS [R01-HL57409] NR 47 TC 40 Z9 41 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAR PY 1999 VL 41 IS 3 BP 510 EP 519 DI 10.1002/(SICI)1522-2594(199903)41:3<510::AID-MRM13>3.0.CO;2-G PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 179GH UT WOS:000079317800013 PM 10204874 ER PT J AU Castle, SC Uyemura, K Crawford, W Wong, W Makinodan, T AF Castle, SC Uyemura, K Crawford, W Wong, W Makinodan, T TI Antigen presenting cell function is enhanced in healthy elderly SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article ID AGE-RELATED-CHANGES; CD4+ T-CELLS; LYMPHOKINE PRODUCTION; IMMUNE-SYSTEM; MICE; ACTIVATION; EXPRESSION; MACROPHAGES; LYMPHOCYTES; RESPONSES AB Aging is associated with a progressive decline in T cell-mediated immune responses. Little is known about the effect of aging on antigen presenting cells (APC). We have recently reported an age-related decline in proliferative response of peripheral blood mononuclear cells from elderly volunteers to Staphylococcus enterotoxin B (SEB). Since SEE-induced stimulation of T cells is not restricted by major histocompatibility complex, experiments were conducted in which T cells and APC from young and healthy elderly subjects were combined. We initially demonstrated the decreased SEE-induced proliferative capacity of elderly T cell-elderly APC co-cultures when compared with young T cell-young APC co-cultures. Combination of purified T cells from elderly donors with APC from young donors maintained a reduced T cell proliferative response. Age-related decline in T cell function was also established by the reduced proliferative capacity of elderly T cells co-cultured with a reference monocyte cell line. Surprisingly, co-culture of APC from healthy elderly donors with purified T cells from young donors enhanced T cell proliferation. APC from elderly donors also marginally enhanced the proliferative response of an SEE-specific T cell line. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Multicampus Div Geriatr & Gerontol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Castle, SC (reprint author), Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Multicampus Div Geriatr & Gerontol, 11301 Wilshire Blvd,Bldg 220,Room 314, Los Angeles, CA 90073 USA. NR 28 TC 35 Z9 35 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 MAR 1 PY 1999 VL 107 IS 2 BP 137 EP 145 DI 10.1016/S0047-6374(98)00141-9 PG 9 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 177NF UT WOS:000079215600002 PM 10220042 ER PT J AU Verheijen, MHG Karperien, M Chung, UI van Wijuen, M Heystek, H Hendriks, JAA Veltmaat, JM Lanske, B Li, E Lowik, CWGM de Laat, SW Kronenberg, HM Defize, LHK AF Verheijen, MHG Karperien, M Chung, UI van Wijuen, M Heystek, H Hendriks, JAA Veltmaat, JM Lanske, B Li, E Lowik, CWGM de Laat, SW Kronenberg, HM Defize, LHK TI Parathyroid hormone-related peptide (PTHrP) induces parietal endoderm formation exclusively via the Type I PTH/PTHrP receptor SO MECHANISMS OF DEVELOPMENT LA English DT Review DE embryonal stem cells; homologous recombination; immunohistochemistry; parathyroid hormone parathyroid hormone-related peptide receptor; parathyroid hormone-related peptide; parietal endoderm ID TERATOCARCINOMA STEM-CELLS; MOUSE EMBRYOS; MESSENGER-RNA; RAT UTERUS; TARGETED DISRUPTION; GENE-EXPRESSION; PROTEIN PTHRP; RETINOIC ACID; DIFFERENTIATION; THROMBOMODULIN AB A number of studies suggest a role for PTHrP and the classical PTH/PTHrP receptor (type I) in one of the first differentiation processes in mouse embryogenesis, i.e. the formation of parietal endoderm (PE). We previously reported that although in type I receptor (-/-) embryos PE formation seemed normal, the embryos were smaller from at least day 9.5 p.c. and 60% had died before day 12.5 p.c. Here we show that the observed growth defect commences even earlier, at day 8.5 p.c. Using two novel antibodies, we show that the expression of the type I receptor protein at this stage is confined to extraembryonic endoderm only. In addition, we show that large amounts of PTHrP protein are present in the adjacent trophoblast giant cells, suggesting a paracrine interaction of PTHrP and the type I PTH/PTHrP receptor in PE formation. The involvement in PE differentiation of other recently described receptors for PTHrP would explain a possible redundancy for the type I receptor in PE formation. However, deletion of the type I PTH/PTHrP receptor in ES cells by homologous recombination completely prevents PTHrP-induced PE differentiation. Based upon these observations, we propose that PTHrP and the type I PTH/PTHrP receptor, although not required for the initial formation of PE, are required for its proper differentiation and/or functioning. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. Univ Leiden Hosp, Dept Endocrinol, NL-2300 RC Leiden, Netherlands. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Defize, LHK (reprint author), Netherlands Inst Dev Biol, Hubrecht Lab, Uppsalalaan 8, NL-3584 CT Utrecht, Netherlands. RI Veltmaat, Jacqueline/G-9648-2011 NR 41 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAR PY 1999 VL 81 IS 1-2 BP 151 EP 161 DI 10.1016/S0925-4773(98)00240-8 PG 11 WC Developmental Biology SC Developmental Biology GA 186WW UT WOS:000079754600012 PM 10330492 ER PT J AU Simon, DK Standaert, DG AF Simon, DK Standaert, DG TI Neuroprotective therapies SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; MONOAMINE-OXIDASE-B; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; NERVOUS-SYSTEM; NITRIC-OXIDE; COMPLEX-I; 1-METHYL-4-PHENYLPYRIDINIUM ION; NEURODEGENERATIVE DISEASES; INDUCED DEGENERATION AB Though effective symptomatic therapies for Parkinson's disease exist, currently no treatment is proven to slow the progression of the underlying disease. Our growing understanding of the mechanisms of neuronal models, however, offers hope that neuroprotective strategies will soon be a standard part of the treatment of PD. Current approaches to the development of neuroprotective strategies are based on the hypothesized roles of oxidative stress and excitotoxicity in the degenerative process. in this article, we review evidence in support of these hypotheses as well as attempts to achieve neuroprotection in PD based on these and other mechanisms. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Neurol Serv, Warren 408,Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [KO8NS01971-01] NR 99 TC 29 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 1999 VL 83 IS 2 BP 509 EP + DI 10.1016/S0025-7125(05)70117-6 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 176KW UT WOS:000079151100012 PM 10093591 ER PT J AU Gangi, DM AF Gangi, DM TI Ob-gyn interactive case challenge - A case of sadness and anxiety 9 months postpartum SO MEDSCAPE WOMENS HEALTH LA English DT Article ID THYROIDITIS; COMPLEMENT; DISEASE AB If you were the primary care provider, how would you diagnose: and treat postpartum anxiety and depression in this young, first-time mother? After a normal, uncomplicated pregnancy, this 27-year-old woman developed anxiety and depressed mood, which she was still struggling to control 9 months after the birth of her child. Among the diagnostic possibilities to consider are occult malignancy, diabetes mellitus, and thyroid disorder, as well as major depression/anxiety disorder and postpartum depression. C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. RP Gangi, DM (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU MEDSCAPE INC PI NEW YORK PA 134 WEST 29TH ST, NEW YORK, NY 10001 USA SN 1521-2076 J9 MEDSCAPE WOMENS HEAL JI Medscape Womens Health PD MAR-APR PY 1999 VL 4 IS 2 BP U3 EP U8 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 206VT UT WOS:000080901600001 ER PT J AU Guyon, JR Narlikar, GJ Sif, S Kingston, RE AF Guyon, JR Narlikar, GJ Sif, S Kingston, RE TI Stable remodeling of tailless nucleosomes by the human SWI-SNF complex SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST SWI/SNF COMPLEX; TRANSCRIPTION FACTOR-BINDING; HISTONE AMINO TERMINI; MULTISUBUNIT COMPLEX; FACILITATED BINDING; GENE-PRODUCTS; CELL-CYCLE; CHROMATIN; ACETYLATION; REPRESSION AB The histone N-terminal tails have been shown previously to be important for chromatin assembly, remodeling, and stability. We have tested the ability of human SWI-SNF (hSWI-SNF) to remodel nucleosomes whose tails have been cleaved through a limited trypsin digestion. We show that hSWI-SNF is able to remodel tailless mononucleosomes and nucleosomal arrays, although hSWI-SNF remodeling of tailless nucleosomes is less effective than remodeling of nucleosomes with tails. Analogous to previous observations with tailed nucleosomal templates, we shaw both (i) Chat hSWI-SNF-remodeled trypsinized mononucleosomes and arrays are stable for 30 min in the remodeled conformation after removal of ATP and (ii) that the remodeled tailless mononucleosome can be isolated on a nondenaturing acrylamide gel as a novel species. Thus, nucleosome remodeling by hSWI-SNF can occur via interactions with a tailless nucleosome core. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Univ Notre Dame, Dept Chem & Biochem, Grad Program, Notre Dame, IN 46556 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. NR 67 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 2088 EP 2097 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900047 PM 10022896 ER PT J AU King, FJ Hu, ED Harris, DF Sarraf, P Spiegelman, BM Roberts, TM AF King, FJ Hu, ED Harris, DF Sarraf, P Spiegelman, BM Roberts, TM TI DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ADIPOCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; TYROSINE KINASES; LEPTIN RECEPTOR; GENE-EXPRESSION; 3T3-L1 CELLS; DOMAINS; SPECIFICITY; ACTIVATION; FAMILY AB The Src homology 3 (SH3) motif is found in numerous signal transduction proteins involved in cellular growth and differentiation. We have purified and cloned a novel protein, DEF-1 (differentiation-enhancing factor), from bovine brain by using a Src SH3 affinity column. Ectopic expression of DEF-1 in fibroblasts resulted in the differentiation of a significant fraction of the culture into adipocytes. This phenotype appears to be related to the induction of the transcription factor peroxisome proliferator-activated receptor gamma (PPAR gamma), since DEF-1 NIH 3T3 cells demonstrated augmented levels of PPAR gamma mRNA and, when treated with activating PPAR gamma ligands, efficient induction of differentiation. Further evidence for a role for DEF-1 in adipogenesis was provided by heightened expression of DEF-1 mRNA in adipose tissue isolated from obese and diabetes mice compared to that in tissue isolated from wild-type mice. However, DEF-1 mRNA was detected in multiple tissues, suggesting that the signal transduction pathway(s) in which DEF-1 is involved is not limited to adipogenesis. These results suggest that DEF-1 is an important component of a signal transduction process that is involved in the differentiation of fibroblasts and possibly of other types of cells. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, SM970,1 Jimmy Fund Way, Boston, MA 02115 USA. EM thomas_roberts@dfci.harvard.edu FU NCI NIH HHS [CA43803, CA01934]; NIDDK NIH HHS [R37DK31405, R37 DK031405] NR 68 TC 25 Z9 27 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 2330 EP 2337 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900070 PM 10022919 ER PT J AU Xu, Y Ma, M Ippolito, GC Johnson, RS Speigelman, BM Schroeder, HW Carroll, MC Volanakis, JE AF Xu, Y Ma, M Ippolito, GC Johnson, RS Speigelman, BM Schroeder, HW Carroll, MC Volanakis, JE TI Targeted disruption of the murine factor D gene by homologous recombination SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Div Dev & Clin Immunol, Dept Med, Birmingham, AL 35294 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAR-APR PY 1999 VL 36 IS 4-5 MA 54 BP 292 EP 292 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 208XF UT WOS:000081016600062 ER PT J AU Rosas, HD Koroshetz, WJ Jenkins, BG Chen, YI Hayden, DL Beal, MF Cudkowicz, ME AF Rosas, HD Koroshetz, WJ Jenkins, BG Chen, YI Hayden, DL Beal, MF Cudkowicz, ME TI Riluzole therapy in Huntington's disease (HD) SO MOVEMENT DISORDERS LA English DT Article DE Huntington's disease; riluzole; magnetic resonance spectroscopy; energy metabolism; lactate; chorea ID AMYOTROPHIC-LATERAL-SCLEROSIS; 3-NITROPROPIONIC ACID; STRIATAL DEGENERATION; ENERGY-METABOLISM; H-1-NMR SPECTROSCOPY; N-ACETYLASPARTATE; CONTROLLED TRIAL; MOTOR DEFICITS; IMPAIRMENT; MOVEMENTS AB We conducted a 6-week open-label trial of riluzole (50 mg twice a day) in eight subjects with Huntington's disease. Subjects were evaluated before riluzole treatment, on treatment, and off treatment with the chorea, dystonia, and total functional capacity (TFC) scores from the Unified Huntington's Disease Rating Scale and magnetic resonance spectroscopy measurements of occipital cortex and basal ganglia lactate levels. Adverse events and safety blood and urine tests were assessed throughout the study. All subjects completed the study and riluzole was well tolerated. The age was 45 +/- 10.2 years (mean +/- standard deviation) and the disease duration was 6.1 +/- 4.1 years. The chorea rating score improved by 35% on treatment (p = 0.013) and worsened alter discontinuation of treatment (p = 0.026). There were no significant treatment effects on the dystonia or TFC scores. The baseline occipital and basal ganglia lactate levels were elevated in all subjects; there was a trend toward lower lactate/creatine ratios during riluzole treatment in the basal ganglia spectra but not in occipital cortex spectra. Additional clinical studies of riluzole for both symptomatic and neuroprotective benefit in Huntington's disease are warranted. C1 Massachusetts Gen Hosp, Dept Neurol, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Rosas, HD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurol Serv, Warren 408,32 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01 RR 01066]; NINDS NIH HHS [K08NS01896] NR 27 TC 78 Z9 81 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 1999 VL 14 IS 2 BP 326 EP 330 DI 10.1002/1531-8257(199903)14:2<326::AID-MDS1019>3.0.CO;2-Q PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 243LP UT WOS:000082999400019 PM 10091628 ER EF