FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Passaretti, D Silverman, RP Huang, W Kirchhoff, CH Ashiku, S Randolph, MA Yaremchuk, MJ AF Passaretti, D Silverman, RP Huang, W Kirchhoff, CH Ashiku, S Randolph, MA Yaremchuk, MJ TI Cultured chondrocytes produce injectable tissue-engineered cartilage in hydrogel polymer SO TISSUE ENGINEERING LA English DT Article; Proceedings Paper CT Meeting of the Northeastern-Society-of-Plastic-Surgeons CY OCT 23-25, 1998 CL NEWPORT, RHODE ISLAND SP NE Soc Plast Surgeons ID ARTICULAR CHONDROCYTES; ALGINATE BEADS; CELL-SHAPE; COLLAGEN; TRANSPLANTATION; PHENOTYPE; LOSE AB The purpose of this study was to determine if chondrocytes cultured through several subcultures at very low plating density would produce new cartilage matrix after being reimplanted in vivo with or without a hydrogel polymer scaffold. Chondrocytes were initially plated in low-density monolayer culture, grown to confluence, and passaged four times. After each passage cells were suspended in purified porcine fibrinogen and injected into the subcutaneous space of nude mice while simultaneously polymerizing with thrombin to reach a final concentration of 40 million cells/cc. Controls were made by injecting fresh, uncultured cells with fibrin polymer and by injecting the cultured cells in saline (without polymer). All samples were harvested at 6 weeks. When injected in polymer, both fresh cells and cells that had undergone only one passage in culture produced cartilaginous nodules. Cultured cells did not produce cartilage, regardless of length of time spent in culture, when injected without polymer. Cartilage was also not recovered from samples with cells kept in culture for longer than one passage, even when provided with a polymer matrix. All samples harvested were subjected to histological analysis and assayed for total DNA, glycosaminoglycan (GAG), and type II collagen. There was histological evidence of cartilage in the groups that used fresh cells and cultured cells suspended in fibrin polymer that only underwent one passage. No other group contained areas that would be consistent with cartilage histologically. All experimental samples had a higher percent of DNA than native swine cartilage, and there was no statistical difference between the DNA content of the groups containing cultured or fresh cells in fibrin polymer. Whereas the GAG content of native cartilage was 8.39% of dry weight and fresh cells in fibrin polymer was 12.85%, cultured cells in fibrin polymer never exceded the 2.48% noted from first passage cells. In conclusion, this study demonstrates that porcine chondrocytes that have been cultured in monolayer for one passage will produce cartilage in vivo when suspended in fibrin polymer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WACC 453,32 Fruit St, Boston, MA 02114 USA. FU PHS HHS [R03 45059] NR 17 TC 62 Z9 74 U1 0 U2 9 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD DEC PY 2001 VL 7 IS 6 BP 805 EP 815 DI 10.1089/107632701753337744 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 505FQ UT WOS:000172903100011 PM 11749736 ER PT J AU Barry, MJ AF Barry, MJ TI Evaluation of symptoms and quality of life in men with benign prostatic hyperplasia SO UROLOGY LA English DT Article; Proceedings Paper CT Conference on Evaluation and Management of Benign Prostatic Hyperplasia (BPH) CY MAR 31, 2001 CL CAMBRIDGE, MASSACHUSETTS ID URINARY-TRACT SYMPTOMS; BLADDER OUTLET OBSTRUCTION; SCORE DAN-PSS-1 SYSTEM; ICS-BPH; OF-LIFE; ICSMALE QUESTIONNAIRE; ADMINISTRATION AFFECT; MADSEN-IVERSEN; INDEX; VALIDATION AB Benign prostatic hyperplasia (BPH) is a common histologic condition among older men, which conveys its morbidity through lower urinary tract symptoms and complications, such as acute urinary retention, obstructive uropathy, and urinary tract infections. The mechanisms linking the histologic process and lower urinary tract symptoms remain uncertain; prostatic enlargement and bladder outlet obstruction are involved. However, measurements of prostate size and the severity of bladder outlet obstruction correlate poorly with the severity of lower urinary tract symptoms, The severity of lower urinary tract symptoms associated with BPH can be measured reliably, from the patient's perspective, with a number of validated questionnaires, including the International Prostate Symptom Score, the Danish Prostate Symptom Score, and the International Continence Society (ICS) male questionnaire. In the clinical setting, these questionnaires can be used (1) to assess the severity of symptoms in men with lower urinary tract symptoms that may be attributable to BPH, based on their age and clinical characteristics; and (2) to follow changes in symptoms over time and with treatment. None of these questionnaires can accurately determine whether a symptomatic patient has underlying bladder outlet obstruction. Additional questionnaires are available to measure the impact of lower urinary tract symptoms on men's lives, as well as associated phenomena, such as continence and sexual function, which may be affected by BPH and its treatments. Men with a severe burden of lower urinary tract symptoms often have measurable decrements in overall health-related quality of life, which can be ameliorated by treatment. (C) 2001, Elsevier Science Inc. C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 42 TC 64 Z9 65 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 2001 VL 58 IS 6A SU S BP 25 EP 32 DI 10.1016/S0090-4295(01)01300-0 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 504AE UT WOS:000172833300006 PM 11750246 ER PT J AU Hammond, CS Wasson, JH Walker-Corkery, E Fowler, FJ Barry, MJ AF Hammond, CS Wasson, JH Walker-Corkery, E Fowler, FJ Barry, MJ CA Patient Outcomes Res Team Prostati Dartmouth Coop Primary Care Cooper TI A frequently used patient and physician-directed educational intervention does nothing to improve primary care of prostate conditions SO UROLOGY LA English DT Article ID GENERAL-PRACTICE; GUIDELINES; CANCER; HYPERPLASIA; DECISION; EFFICACY; PROGRAM; IMPACT AB Objectives. To measure the impact of an educational intervention directed at both patients and their primary care physicians about prostate-related conditions. Methods. We used a randomized, control design for 50 physicians in 33 rural primary care practices from New England and Arkansas and a probability sample of 2402 of their male patients. For the physicians, we mailed two newsletters, conducted two face-to-face research staff visits, and provided printed educational manuals about the management of prostate conditions. For the patients, mailed educational pamphlets were targeted to the baseline symptom levels. After 18 months, 87% of patients and 92% of physicians completed a final survey. The patient survey measured health status, urinary symptoms and bother, treatments received, and prostate-related knowledge. The final physician survey asked them about their management of common prostate conditions. Results. Before randomization, most men (59%) said they knew little or nothing about prostate problems that affect urination, and 63% also reported "little" or "no" knowledge about prostate-specific antigen testing. Eighteen months later, we observed no differences between the intervention and control patients in the measures of health status, urinary symptoms and bother, treatments received, and prostate-related knowledge. The intervention, physicians' knowledge, and self-reported practices for managing common prostate conditions were no better than the control physicians', Conclusions. This commonly used education strategy had no measurable impact on prostate-related care. UROLOGY 58: 875-881, 2001. (C) 2001, Elsevier Science Inc. C1 Dartmouth Coll, Sch Med, Dartmouth Primary Care Cooperat Res Network, Hanover, NH 03755 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Boston, MA 02125 USA. RP Wasson, JH (reprint author), Dartmouth Coll, Sch Med, Dartmouth Primary Care Cooperat Res Network, Hanover, NH 03755 USA. FU AHRQ HHS [HS 08397] NR 30 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 2001 VL 58 IS 6 BP 875 EP 881 DI 10.1016/S0090-4295(01)01438-8 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 502PP UT WOS:000172752200009 PM 11744449 ER PT J AU Bubolz, T Wasson, JH Lu-Yao, G Barry, MJ AF Bubolz, T Wasson, JH Lu-Yao, G Barry, MJ TI Treatments for prostate cancer in older men: 1984-1997 SO UROLOGY LA English DT Article ID RADICAL PROSTATECTOMY; NATIONAL SURVEY; UROLOGISTS; BELIEFS AB Objectives. To examine the temporal trends in radical prostatectomy (RP), brachytherapy (137), and external beam radiotherapy (EBRT) rates a mo ng men aged 65 years or older for the period 1984 to 1997. Methods. We used the retrospective population-based analysis of treatments for prostate cancer among Medicare beneficiaries. The rates of RP were obtained from Part A (hospital) Medicare data for 20% of the national sample for 1984 to 1997. The BT and EBRT rates for the period 1993 to 1997 were obtained from a 5% national sample of Physician/Supplier Part B data. The rates of treatment, 30-day mortality, and readmissions were included. Results. The rate of RP peaked in 1992. From 1993 to 1997, its use decreased by 6% among men aged 65 to 69 years, 34% among men aged 70 to 74 years, and 50% for men aged 75 years or older. However, by 1997, the RP + BT treatment rate again approached the 1992 levels of RP alone; BT was used twice as often as RP in men aged 75 years or older. By 1997, the RP + BT EBRT rate exceeded the 1993 rate for men aged 65 to 69 years and was again approaching the 1993 rate for men aged 70 to 74 years. From 1984 to 1997, the presence of comorbid conditions gradually declined for RP and accounted for more than 60% of the decrease in the short term mortality during this period. Variations in RP use by geographic region have also decreased. Conclusions. RP is now more selectively targeted for treatment of prostate cancer in men older than 70 years than in the past. However, since BT has been substituted for radical surgery in many of these older men, the total population-based treatment rates have changed very little over time. UROLOGY 58: 977-982, 2001. (C) 2001, Elsevier Science Inc. C1 Dartmouth Coll, Sch Med, Cooperat Res Network, Hanover, NH 03755 USA. Healthstat, Princeton, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wasson, JH (reprint author), Dartmouth Coll, Sch Med, Cooperat Res Network, 7265 Butler Bldg, Hanover, NH 03755 USA. FU AHRQ HHS [HS 08397] NR 15 TC 50 Z9 50 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD DEC PY 2001 VL 58 IS 6 BP 977 EP 982 DI 10.1016/S0090-4295(01)01434-0 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 502PP UT WOS:000172752200032 PM 11744472 ER PT J AU Pinsky, LE Burke, W Bird, TD AF Pinsky, LE Burke, W Bird, TD TI Why should primary care physicians know about the genetics of dementia? SO WESTERN JOURNAL OF MEDICINE LA English DT Article ID APOLIPOPROTEIN-E GENOTYPE; PLACEBO-CONTROLLED TRIAL; E EPSILON-4 ALLELE; ALZHEIMERS-DISEASE; FAMILIAL AGGREGATION; TACRINE THERAPY; AD; POPULATION; DIAGNOSIS; RISK C1 Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med Hist & Eth, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Pinsky, LE (reprint author), Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Box 354760,1959 NE Pacific, Seattle, WA 98195 USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD DEC PY 2001 VL 175 IS 6 BP 412 EP 416 DI 10.1136/ewjm.175.6.412 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 497PB UT WOS:000172463700021 PM 11733436 ER PT J AU Sudhakar, S Li, Y Katz, MS Elango, N AF Sudhakar, S Li, Y Katz, MS Elango, N TI Translational regulation is a control point in RUNX2/Cbfa1 gene expression SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE osteoblast differentiation; RUNX2 transcription factor; isoforms; type-specific antibodies; translational regulation ID TRANSCRIPTION FACTOR; OSTEOBLAST DIFFERENTIATION; CLEIDOCRANIAL DYSPLASIA; BONE-FORMATION; CELL-LINES; CBFA1; AML1; OSF2/CBFA1; PHENOTYPE; ISOFORMS AB Runt-related transcription factor-2 (RUNX2)/core binding factor al (Cbfa1) is implicated in the regulation of osteoblast differentiation and osteoblast-specific gene expression. Mutations in RUNX2 cause the bone disease cleidocranial dysplasia, which is characterized by multiple skeletal defects. RUNX2 is expressed as two isoforms (type-I and type-II) encoded by two different mRNAs. We report here the detection of both mRNAs in osteoblastic cells and osteoblast precursors as well as nonosteoblastic cells. Surprisingly, however, osteoblast precursors and nonosteoblastic cells express no RUNX2 protein; mature osteoblasts express both isoforms, while less mature osteoblastic cells express only type-I protein. Northern blot analysis of RNA isolated from polysomes and ribonucleoprotein particles demonstrated that RUNX2 mRNA is polysome-associated in osteoblastic cells but polysome-free in osteoblast precursors. These results suggest that (a) RUNX2 mRNAs are expressed but dormant in osteoblast precursors and nonosteoblastic cells, (b) RUNX2 gene expression is controlled at the translational level, and (c) the expression of individual protein isoforms of RUNX2 is differentiation stage specific. Thus, differentiation of cells along the osteoblast lineage appears to be regulated at the level of RUNX2 mRNA translation. (C) 2001 Elsevier Science. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. RP Elango, N (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. NR 38 TC 42 Z9 43 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 NOV 30 PY 2001 VL 289 IS 2 BP 616 EP 622 DI 10.1006/bbrc.2001.6033 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 500CG UT WOS:000172607900048 PM 11716520 ER PT J AU Polyak, K AF Polyak, K TI On the birth of breast cancer SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE breast cancer; tumor progression; DCIS (ductal carcinoma in situ); pre-invasive lesions ID CARCINOMA IN-SITU; MAMMARY EPITHELIAL-CELLS; COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN MYOEPITHELIAL CELL; SURGICAL ADJUVANT BREAST; TUMOR-SUPPRESSOR; PROMOTER HYPERMETHYLATION; PROGESTERONE RECEPTORS; EXTRACELLULAR-MATRIX; SUSCEPTIBILITY GENE AB Breast carcinoma is one of the most common neoplasms in women and is a leading cause of cancer related deaths worldwide. In recent years improved diagnostic tools have made it possible to detect breast cancers at early, even pre-invasive stages leading to a significant decrease in breast cancer mortality rates over the past decades. The increased number of patients diagnosed with pre-invasive breast tumors opened up new avenues in research and new dilemmas in clinical practice, since our understanding of the pathophysiology of such lesions is just beginning to emerge. Part of the delay and difficulty with analyzing pre-invasive tumors including ductal carcinoma in situ has been due to the lack of appropriate techniques suitable for studies of small, frequently microscopic size tumors. Recently developed technologies such as DNA microarrays and SAGE (serial analysis of gene expression) have made it possible to obtain comprehensive gene expression profiles of breast carcinomas of all stages. The application of these genomics approaches in combination with the complete sequence of the human genome and extensive molecular epidemiological studies is likely to further our understanding of the molecular basis of mammary tumorigenesis and will identify targets for risk prediction, cancer prevention and treatment. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 107 TC 35 Z9 35 U1 1 U2 4 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 NOV 30 PY 2001 VL 1552 IS 1 BP 1 EP 13 DI 10.1016/S0304-419X(01)00029-4 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 519AQ UT WOS:000173701600001 PM 11781111 ER PT J AU Chai, YH Wu, LZ Griffin, JD Paulson, HL AF Chai, YH Wu, LZ Griffin, JD Paulson, HL TI The role of protein composition in specifying nuclear inclusion formation in polyglutamine disease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MACHADO-JOSEPH-DISEASE; CREB-BINDING-PROTEIN; SCA1 TRANSGENIC MICE; HUNTINGTONS-DISEASE; EXPANDED POLYGLUTAMINE; MOUSE MODEL; GENE-PRODUCT; IN-VITRO; NEURODEGENERATIVE DISEASES; INTRANUCLEAR INCLUSIONS AB Intracellular inclusions are a unifying feature of polyglutamine (polyQ) neurodegenerative diseases, yet each polyQ disease displays a unique pattern of neuronal degeneration. This implies that the protein context of expanded polyQ plays an important role in establishing selective neurotoxicity. Here, in studies of the spinocerebellar ataxia type 3 disease protein ataxia-3, we demonstrate that the protein sequence surrounding polyQ specifies the constituents of nuclear inclusions (NI) formed by the disease protein. The nuclear proteins cAMP response element-binding protein-binding protein (CBP) and Mastermind-like-1 strongly colocalize only to NI formed by full-length ataxia-3, whereas the splicing factor SC35 colocalizes only to NI formed by a polyQ-containing, carboxyl-terminal fragment of ataxia-3. These differences in NI formation reflect specific protein interactions normally undertaken by ataxia-3, as both normal and mutant full-length ataxia-3 co-immunoprecipitate with CBP and sediment on density gradients as macromolecular complexes. Moreover, normal ataxia-3 represses cAMP response element-binding protein-mediated transcription, indicating a functional consequence of ataxia-3 interactions with CBP. Finally, we show that mutant ataxia-3 forms insoluble intranuclear complexes, or MIL croaggregates, before NI can be detected, implying a precursor-product relationship. These results suggest that protein context-dependent recruitment of nuclear proteins to intranuclear microaggregates, and subsequently to NI, may contribute to selective neurotoxicity in polyQ diseases. C1 Univ Iowa, Coll Med, Dept Neurol, Iowa City, IA 52242 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Paulson, HL (reprint author), Univ Iowa, Coll Med, Dept Neurol, Iowa City, IA 52242 USA. FU NINDS NIH HHS [NS38712] NR 55 TC 76 Z9 78 U1 0 U2 3 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 NOV 30 PY 2001 VL 276 IS 48 BP 44889 EP 44897 DI 10.1074/jbc.M106575200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 496QD UT WOS:000172406700075 PM 11572863 ER PT J AU Tekirian, TL Merriam, DE Marshansky, V Miller, J Crowley, AC Chan, H Ausiello, D Brown, D Buxbaum, JD Xia, WM Wasco, W AF Tekirian, TL Merriam, DE Marshansky, V Miller, J Crowley, AC Chan, H Ausiello, D Brown, D Buxbaum, JD Xia, WM Wasco, W TI Subcellular localization of presenilin 2 endoproteolytic C-terminal fragments SO MOLECULAR BRAIN RESEARCH LA English DT Article DE presenilin; processing; Alzheimer's; cleavage; endoplasmic reticulum; trans-Golgi network ID DISEASE-ASSOCIATED PRESENILIN-1; FAMILIAL ALZHEIMERS-DISEASE; AMYLOID PRECURSOR PROTEIN; ENDOPLASMIC-RETICULUM; RETROGRADE TRANSPORT; SHIGA TOXIN; GOLGI-APPARATUS; INTERMEDIATE COMPARTMENT; DISTINCT POPULATIONS; MISSENSE MUTATIONS AB Mutations in the genes that encode the presenilin 1 and 2 (PS1 and PS2) proteins cause the majority of familial Alzheimer's disease (FAD). Differential cleavage of the presenilins results in a generation of at least two C-terminal fragments (CTFs). An increase in the smaller of these two CTFs is one of the few changes in presenilin processing associated with FAD mutations in both PS1 and PS2. Interestingly, the phosphorylation of PS2 modulates the production of the smaller, caspase-derived PS2 CTF. which indicates that the generation of this fragment is a regulated. physiologic event. To date, there is no data concerning the subcellular distribution of the caspase-derived PS2 CTF. Because this fragment is normally present at levels that are difficult to detect, we have used cell lines in which the production of wild-type or N1411 mutant PS2 is controlled by a tetracycline-regulated promoter in order to assess the subcellular localization of the caspase CTF in relation to the larger. constitutive PS2 CTF and to PS2 holoprotein. We have found that when levels of PS2 are low. the constitutive CTF colocalizes with markers consistent with localization in the early Golgi-ER-Golgi intermediate compartment (ERGIC) while the caspase CTF colocalizes with markers for the endoplasmic reticulum (ER). Following induction of wild-type or mutant PS2, when the levels of PS2 are high, the primary localization of the constitutive CTF appears to shift from the early Golgi-ERGIC in addition to the ER. Interestingly, while the induction of wild-type PS2 resulted in the localization of the caspase CTF primarily in the ER. the induction of mutant PS2 resulted in the localization of the caspase CTF to both the ER and the early Golgi-ERGIC. In summary, these data suggest that the two presenilin 2 CTFs have different patterns of subcellular localization and that the N1411 PS2 mutation alters the localization pattern of the PS2 caspase fragment. (C) 2001 Published by Elsevier Science. B.V. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol Genet & Aging Unit, Charlestown, MA 02129 USA. Renal Unit, Charlestown, MA 02129 USA. Dept Membrane BIol, Charlestown, MA 02129 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. Harvard Univ, Brigham & Womens Hosp, Inst Med, Sch Med,Ctr Neurol Dis, Boston, MA 02115 USA. RP Tekirian, TL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol Genet & Aging Unit, Charlestown, MA 02129 USA. RI xia, weiming/E-5465-2016; OI xia, weiming/0000-0002-7463-3295; Buxbaum, Joseph/0000-0001-8898-8313 NR 49 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD NOV 30 PY 2001 VL 96 IS 1-2 BP 14 EP 20 DI 10.1016/S0169-328X(01)00250-9 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 505HW UT WOS:000172908200002 ER PT J AU Leishman, AJ Naidenko, OV Attinger, A Koning, F Lena, CJ Xiong, Y Chang, HC Reinherz, E Kronenberg, M Cheroutre, H AF Leishman, AJ Naidenko, OV Attinger, A Koning, F Lena, CJ Xiong, Y Chang, HC Reinherz, E Kronenberg, M Cheroutre, H TI T cell responses modulated through interaction between CD8 alpha alpha and the nonclassical MHC class I molecule, TL SO SCIENCE LA English DT Article ID THYMUS LEUKEMIA ANTIGEN; LYMPHOCYTES; EXPRESSION; CD8; MOUSE; SELECTION; RECEPTORS; MICE; VIVO AB The thymus leukemia antigen (TL) is a nonclassical class I molecule, expressed abundantly on intestinal epithelial cells. We show that, in contrast to other major histocompatibility complex (MHC) class I molecules that bind CD8 alpha beta, TL preferentially binds the homotypic form of CD8 alpha (CD8 alpha alpha). Thus, TL tetramers react specifically to CD8 alpha alpha -expressing cells, including most intestinal intraepithelial lymphocytes. Compared with CD8 alpha beta, which recognizes the same MHC as the T cell, receptor (TCR) and thus acts as a TCR coreceptor, high-affinity binding of CD8 alpha alpha to TL modifies responses mediated by TCR recognition of antigen presented by distinct MHC molecules. These findings define a novel mechanism of lymphocyte regulation through CD8 alpha alpha and MHC class I. C1 La Jolla Inst Allergy & Immunol, Div Dev Immunol, San Diego, CA 92121 USA. Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Cheroutre, H (reprint author), La Jolla Inst Allergy & Immunol, Div Dev Immunol, 10355 Sci Ctr Dr, San Diego, CA 92121 USA. FU NCI NIH HHS [CA52511]; NIAID NIH HHS [AI 19807, AI50263]; NIDDK NIH HHS [DK54451] NR 23 TC 170 Z9 174 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 30 PY 2001 VL 294 IS 5548 BP 1936 EP 1939 DI 10.1126/science.1063564 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 497PQ UT WOS:000172465000062 PM 11729321 ER PT J AU Poldrack, RA Clark, J Pare-Blagoev, EJ Shohamy, D Moyano, JC Myers, C Gluck, MA AF Poldrack, RA Clark, J Pare-Blagoev, EJ Shohamy, D Moyano, JC Myers, C Gluck, MA TI Interactive memory systems in the human brain SO NATURE LA English DT Article ID EVENT-RELATED FMRI; CAUDATE-NUCLEUS; HIPPOCAMPUS; ACQUISITION; AMNESIA; LESIONS; PLACE; RATS AB Learning and memory in humans rely upon several memory systems, which appear to have dissociable brain substrates(1,2). A fundamental question concerns whether, and how, these memory systems interact. Here we show using functional magnetic resonance imaging (FMRI) that these memory systems may compete with each other during classification learning in humans. The medial temporal lobe and basal ganglia were differently engaged across subjects during classification learning depending upon whether the task emphasized declarative or nondeclarative memory, even when the to-be-learned material and the level of performance did not differ. Consistent with competition between memory systems suggested by animal studies(3,4) and neuroimaging(5), activity in these regions was negatively correlated across individuals. Further examination of classification learning using event-related FMRI showed rapid modulation of activity in these regions at the beginning of learning, suggesting that subjects relied upon the medial temporal lobe early in learning. However, this dependence rapidly declined with training, as predicted by previous computational models of associative learning(6-8). C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02131 USA. Harvard Univ, Sch Med, Charlestown, MA 02131 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA. Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA. RP Poldrack, RA (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02131 USA. OI Myers, Catherine/0000-0002-2776-4823 NR 29 TC 564 Z9 569 U1 5 U2 50 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 29 PY 2001 VL 414 IS 6863 BP 546 EP 550 DI 10.1038/35107080 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 496PV UT WOS:000172405900048 PM 11734855 ER PT J AU Wildermuth, MC Dewdney, J Wu, G Ausubel, FM AF Wildermuth, MC Dewdney, J Wu, G Ausubel, FM TI Isochorismate synthase is required to synthesize salicylic acid for plant defence SO NATURE LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; GENE-EXPRESSION; TRANSCRIPTION FACTORS; DISEASE RESISTANCE; ARABIDOPSIS; TOBACCO; BIOSYNTHESIS; INDUCTION; MUTANT; PROTEIN AB Salicylic acid (SA) mediates plant defences against pathogens, accumulating in both infected and distal leaves in response to pathogen attack(1-5). Pathogenesis-related gene expression and the synthesis of defensive compounds associated with both local and systemic acquired resistance (LAR and SAR) in plants require SA. In Arabidopsis, exogenous application of SA suffices to establish SAR, resulting in enhanced resistance to a variety of pathogens. However, despite its importance in plant defence against pathogens, SA biosynthesis is not well defined. Previous work has suggested that plants synthesize SA from phenylalanine(6-10); however, SA could still be produced when this pathway was inhibited(6,8), and the specirc activity of radiolabelled SA in feeding experiments was often lower than expected(7,8). Some bacteria such as Pseudomonas aeruginosa synthesize SA using isochorismate synthase (ICS) and pyruvate lyase(11). Here we show, by cloning and characterizing an Arabidopsis defence-related gene (SID2) defined by mutation, that SA is synthesized from chorismate by means of ICS, and that SA made by this pathway is required for LAR and SAR responses. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Brandeis Univ, Michtom Sch Comp Sci, Waltham, MA 02254 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RI allasia, valerie/B-4214-2009 NR 30 TC 890 Z9 940 U1 17 U2 115 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 29 PY 2001 VL 414 IS 6863 BP 562 EP 565 DI 10.1038/35107108 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 496PV UT WOS:000172405900052 PM 11734859 ER PT J AU Swartz, MN AF Swartz, MN TI Current concepts - Recognition and management of anthrax - An update SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID INHALATION ANTHRAX; BACILLUS-ANTHRACIS C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Swartz, MN (reprint author), Massachusetts Gen Hosp, Dept Med, Bullfinch 127,55 Fruit St, Boston, MA 02114 USA. NR 12 TC 171 Z9 177 U1 0 U2 10 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 NOV 29 PY 2001 VL 345 IS 22 BP 1621 EP 1626 DI 10.1056/NEJMra012892 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 496EU UT WOS:000172383900007 PM 11704686 ER PT J AU Yawetz, S Mark, EJ Aquino, SLH Colvin, RB AF Yawetz, S Mark, EJ Aquino, SLH Colvin, RB TI A 76-year-old man with fever, dyspnea, pulmonary infiltrates, pleural effusions, and confusion - Ehrlichiosis, human granulocytic form. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MYCOPLASMA-PNEUMONIAE INFECTION; RESPIRATORY-DISTRESS-SYNDROME; COMMUNITY-ACQUIRED PNEUMONIA; TICK-BORNE DISEASES; CHLAMYDIA-PNEUMONIAE; UNITED-STATES; LYME-DISEASE; BABESIOSIS; THROMBOCYTOPENIA; CHAFFEENSIS C1 Brigham & Womens Hosp, Infect Dis Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yawetz, S (reprint author), Brigham & Womens Hosp, Infect Dis Serv, 75 Francis St, Boston, MA 02115 USA. NR 39 TC 3 Z9 3 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 NOV 29 PY 2001 VL 345 IS 22 BP 1627 EP 1634 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 496EU UT WOS:000172383900008 ER PT J AU Han, XS Stewart, JE Bellis, SL Benveniste, EN Ding, Q Tachibana, K Grammer, JR Gladson, CL AF Han, XS Stewart, JE Bellis, SL Benveniste, EN Ding, Q Tachibana, K Grammer, JR Gladson, CL TI TGF-beta 1 up-regulates paxillin protein expression in malignant astrocytoma cells: requirement for a fibronectin substrate SO ONCOGENE LA English DT Article DE paxillin; TGF-beta 1; fibronectin; integrin alpha 5 beta 1; astrocytoma; astrocytes; glioma; glioblastoma ID INTEGRIN; GENE; VITRONECTIN; ACTIVATION; SENESCENCE; MOLECULES; COMPLEX; DOCK180; KINASE; HIC-5 AB Cytokines can influence the interactions between members of the integrin cell adhesion receptor family and the extracellular matrix thereby potentially affecting cell function and promoting cell adhesion, growth and migration of malignant astrocytoma tumor cells. As malignant astrocytoma cells synthesize TGF-beta1 in vivo, we analysed the effects of TGF-beta1 on signaling events associated with integrin receptor ligation, focusing on the effects on paxillin, a phosphorylated adaptor protein, that acts as a scaffold for signaling molecules recruited to focal adhesions. TGF-beta1 -stimulation of primary astrocytes and serum-starved U-251MG malignant astrocytoma cells attached to fibronectin induced a substantial increase in the levels of paxillin protein (fivefold increase at 2.0 ng/ml) in a dose- and time-dependent manner compared to the levels observed on plating onto fibronectin in the absence of stimulation. In the astrocytoma cells, this resulted in an increase in the pool of tyrosine-phosphorylated paxillin, although it did not appear to alter the extent of phosphorylation of the paxillin molecules. In contrast, in primary astrocytes the protein levels were upregulated in the absence of a parallel increase in phosphorylation. The TGF-beta1-stimulated increase in paxillin levels required ligation of the fibronectin receptor, as it was not induced when the cells were plated onto vitronectin, collagen or laminin. The increase in the pool of paxillin on TGF-beta1 stimulation of the fibronectin-plated astrocytoma cells was associated with an increase in translation, but was not associated with an increase in the steady-state levels of paxillin mRNA. Stimulation with TGF-beta1 on a fibronectin substrate increased subsequent attachment and spreading of U-251MG cells onto fibronectin and, to a lesser extent, vitronectin, but not collagen. Our results indicate that physiologic levels of TGF-beta1 stimulate the expression of paxillin protein at the level of translation through a process that requires engagement of the fibronectin receptor, and promotes attachment and spreading of malignant astrocytoma cells on fibronectin. C1 Univ Alabama, Dept Pathol, Div Neuropathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Gladson, CL (reprint author), Univ Alabama, Dept Pathol, Div Neuropathol, LHRB 567,701 S 19th St, Birmingham, AL 35294 USA. FU NCI NIH HHS [CA59958, CA75682]; NINDS NIH HHS [NS34856] NR 20 TC 19 Z9 20 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 29 PY 2001 VL 20 IS 55 BP 7976 EP 7986 DI 10.1038/sj.onc.1204996 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 494NL UT WOS:000172288700006 PM 11753680 ER PT J AU Topol, EJ McCarthy, J Gabriel, S Moliterno, DJ Rogers, WJ Newby, LK Freedman, M Metivier, J Cannata, R O'Donnell, CJ Kottke-Marchant, K Murugesan, G Plow, EF Stenina, O Daley, GQ AF Topol, EJ McCarthy, J Gabriel, S Moliterno, DJ Rogers, WJ Newby, LK Freedman, M Metivier, J Cannata, R O'Donnell, CJ Kottke-Marchant, K Murugesan, G Plow, EF Stenina, O Daley, GQ CA GeneQuest Investigators Collaborat TI Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction SO CIRCULATION LA English DT Article; Proceedings Paper CT 73rd Annual Scientific Sessions of the American-Heart-Association CY NOV 12-15, 2000 CL NEW ORLEANS, LA SP Amer Heart Assoc DE genetics; coronary disease; myocardial infarction; atherosclerosis; genes ID CORONARY-ARTERY DISEASE; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; MATRICELLULAR PROTEINS; VENOUS THROMBOSIS; INCREASED RISK; FACTOR-V; MUTATION; MEN; EXPRESSION; CARRIERS AB Background-Recent advances in high-throughput genomics technology have expanded our ability to catalogue allelic variants in large sets of candidate genes related to premature coronary artery disease. Methods and Results-A total of 398 families were identified in 15 participating medical centers; they fulfilled the criteria of myocardial infarction, revascularization, or a significant coronary artery lesion diagnosed before 45 years in men or 50 years in women. A total of 62 vascular biology genes and 72 single-nucleotide polymorphisms were assessed. Previously undescribed variants in 3 related members of the thrombospondin protein family were prominent among a small set of single-nucleotide polymorphisms that showed a statistical association with premature coronary artery disease. A missense variant of thrombospondin 4 (A387P) showed the strongest association, with an adjusted odds ratio for myocardial infarction of 1.89 (P=0.002 adjusted for covariates) for individuals carrying the P allele. A variant in the 3' untranslated region of thrombospondin-2 (change of thymidine to guanine) seemed to have a protective effect against myocardial in individuals homozygous for the variant (adjusted odds ratio of 0.31; P=0.0018). A missense variant in thrombospondin-1 (N700S) was associated with an adjusted odds ratio for coronary artery disease of 11.90 (P=0.041) in homozygous individuals, who also had the lowest level of thrombospondin-1 by plasma assay (P=0.0019). Conclusions-This large-scale genetic study has identified the potential of multiple novel variants in the thrombospondin gene family to be associated with familial premature myocardial infarction. Notwithstanding multiple caveats, thrombospondins specifically and high-throughput genomic technology in general deserve further study in familial ischemic heart disease. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Boston, MA USA. Univ Alabama Birmingham, Ctr Med, Birmingham, AL USA. Duke Univ, Ctr Med, Durham, NC USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Topol, EJ (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, 9500 Euclid Ave,Desk F25, Cleveland, OH 44195 USA. EM topole@ccf.org OI Topol, Eric/0000-0002-1478-4729 NR 24 TC 193 Z9 209 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 27 PY 2001 VL 104 IS 22 BP 2641 EP 2644 DI 10.1161/hc4701.100910 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 497BH UT WOS:000172432500023 PM 11723011 ER PT J AU Jang, IK Tearney, G Bouma, B AF Jang, IK Tearney, G Bouma, B TI Visualization of tissue prolapse between coronary stent struts by optical coherence tomography - Comparison with intravascular ultrasound SO CIRCULATION LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 78 Z9 88 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 NOV 27 PY 2001 VL 104 IS 22 BP 2754 EP 2754 DI 10.1161/hc4701.098069 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 497BH UT WOS:000172432500043 PM 11723031 ER PT J AU Wagner, AD Davachi, L AF Wagner, AD Davachi, L TI Cognitive neuroscience: Forgetting of things past SO CURRENT BIOLOGY LA English DT Article ID RECOGNITION MEMORY; BRAIN ACTIVITY; INSIGHTS; SYSTEMS; CORTEX AB Recent functional imaging and electrophysiological results indicate that failure to remember experiences can result from a decreased recruitment of encoding processes that build effective memories and an increased recruitment of alternative mechanisms that may impair effective learning. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Ctr Learning & Memory, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02114 USA. RP Wagner, AD (reprint author), MIT, Dept Brain & Cognit Sci, NE20-463, Cambridge, MA 02139 USA. FU NIDCD NIH HHS [DC04466] NR 28 TC 67 Z9 67 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 27 PY 2001 VL 11 IS 23 BP R964 EP R967 DI 10.1016/S0960-9822(01)00575-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 497VG UT WOS:000172475700009 PM 11728323 ER PT J AU Shefner, JM Brown, RH Cole, D Chaturvedi, P Schoenfeld, D Pastuszak, K Matthews, R Upton-Rice, M Cudkowicz, ME AF Shefner, JM Brown, RH Cole, D Chaturvedi, P Schoenfeld, D Pastuszak, K Matthews, R Upton-Rice, M Cudkowicz, ME TI Effect of neurophilin ligands on motor units in mice with SOD1 ALS mutations SO NEUROLOGY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the American-Academy-of-Neurology CY APR 29-MAY 06, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Acad Neurol ID AMYOTROPHIC-LATERAL-SCLEROSIS; NERVE REGENERATION; NUMBER; MUSCLE; NEURONS; CULTURE AB Background: Mice with trangenes that express mutations in the gene for cytosolic copper/zinc superoxide dismutase (SOD1) develop motor neuron degeneration resembling human ALS. Neurophilin ligands are small molecules that promote neurite outgrowth. Objective: To test the hypothesis that treatment with two neurophilin ligands increases survival in these ALS mice by slowing the loss of motor neurons and increasing the sizes of motor units. Methods: Transgenic mice hemizygous for the G93A mutation were untreated or treated from 30 days of age with one of two doses of two neurophilin ligands (V-13,670; V-10,367, Vertex Pharmaceuticals, Boston, MA). Onset of behavioral abnormalities and survival were recorded. Motor unit number estimation (MUNE) was performed every 21 days starting at age 60 days. Results: In control animals, disease onset occurred at 77.0 days of age and death occurred at 137 days of age. Neither neurophilin ligand affected the disease course. In control animals, MUNE declined with time beginning before behavioral abnormalities were noted, and motor unit size increased concomitantly. There was no effect of drug on motor unit loss as assessed by MUNE; however, motor unit size increased more rapidly and to a greater degree in animals treated with V-13,670. Conclusion: As in human ALS, the transgenic ALS mice show physiologic changes in the motor unit prior to the development of clinical signs: MUNE declines as motor unit size increases. Although neither neurophilin ligand significantly affected survival, one produced an increase in motor unit size. The fact that survival was not altered by the increase in motor unit size may reflect the rapid disease course in this animal model. C1 Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA. Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Clin Trial Unit, Boston, MA 02114 USA. Vertex Pharmaceut, Boston, MA USA. RP Shefner, JM (reprint author), Upstate Med Univ, Dept Neurol, 750 E Adams St, Syracuse, NY 13210 USA. NR 21 TC 26 Z9 26 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 NOV 27 PY 2001 VL 57 IS 10 BP 1857 EP 1861 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 495HP UT WOS:000172334700021 PM 11723276 ER PT J AU Mylonakis, E Goes, N Rubin, RH Cosimi, AB Colvin, RB Fishman, JA AF Mylonakis, E Goes, N Rubin, RH Cosimi, AB Colvin, RB Fishman, JA TI BK virus in solid organ transplant recipients: An emerging syndrome SO TRANSPLANTATION LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; RENAL-ALLOGRAFT RECIPIENTS; POLYMERASE CHAIN-REACTION; BONE-MARROW TRANSPLANTS; POLYOMAVIRUS TYPE BK; JC-VIRUS; HEMORRHAGIC CYSTITIS; INTERSTITIAL NEPHRITIS; TUBULAR-NECROSIS; INFECTION AB BK virus is a human polyomavirus associated with a range of clinical presentations from asymptomatic viruria with pyuria to ureteral ulceration with ureteral stenosis in renal transplant patients or hemorrhagic cystitis in bone marrow transplant recipients. Infection of renal allografts has been associated with diminished graft function in some individuals. Fortunately, however, the majority of patients with BK virus infections are asymptomatic. The type, duration, and intensity of immunosuppression are major contributors to susceptibility to the activation of BK virus infection. Histopathology is required for the demonstration of renal parenchymal involvement; urine cytology and viral polymerase chain reaction methods are useful adjunctive diagnostic tools. Current, treatment of immunosuppressed patients with polyomavirus viruria is largely supportive and directed toward minimizing immunosuppression. Improved diagnostic tools and antiviral therapies are needed for polyomavirus infections. C1 Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Transplant Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 48 TC 98 Z9 102 U1 1 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 NOV 27 PY 2001 VL 72 IS 10 BP 1587 EP 1592 DI 10.1097/00007890-200111270-00001 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 500EZ UT WOS:000172614200001 PM 11726814 ER PT J AU Zhao, Y Rodriguez-Barbosa, JI Swenson, K Zhao, GL Arn, JS Sykes, M AF Zhao, Y Rodriguez-Barbosa, JI Swenson, K Zhao, GL Arn, JS Sykes, M TI Highly disparate xenogeneic skin graft tolerance induction by fetal pig thymus in thymectomized mice - Conditioning requirements and the role of coimplantation of fetal pig liver SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; XENOGRAFT REJECTION; TRANSPLANTATION; BARRIER; CELLS; ANTIBODIES; CHIMERAS; DONOR AB Background. Highly disparate xenogeneic pig ski graft tolerance and efficient repopulation. of mouse CD4(+) T cells are achieved in thymectomized (ATX) B6 mice that receive T cell and natural killer (NK) cell depletion by injection of a mixture of monoclonal antibodies (mAbs) (GK1.5, 2.43, 30-H12, and PK136) on days -6, -1, +7, and +14 and 3 Gy total body irradiation (TBI) followed by implantation of fetal pig thymus/liver (FP THY/LIV) grafts on day 0. The requirements for each treatment in this model to achieve pig skin graft tolerance have not previously been defined Therefore, we performed a series of experiments to address the role of each treatment in achieving maxi mal skin graft tolerance. Methods. Peripheral mouse CD4+ T-cell repopulation and pig skin graft survival were followed in this pig-to-mouse model in which recipient B6 mice were treated with modified regimens that omitted thymectomy, 3 Gy TBI, anti-Thy1.2, and anti-NK1.1 mAbs, injection of a mixture of mAbs on day +14, or coimplantation of FP LIV, respectively. Results. Prolongation but not permanent survival of donor MHC-matched pig skin grafts was observed in euthymic B6 mice that received T and NK cell depletion, 3 Gy TBI, and 7 Gy thymic irradiation and FB THY/LIV in the mediastinum, suggesting that full xenogeneic tolerance was not achieved in euthymic mice. However, after grafting FP THY alone to ATX B mice treated either with the "standard" regimen, or with a conditioning regimen that omitted all components of the conditioning regimen except treatment with anti-CD4 and anti-CD8 mAbs, efficient peripheral repopulation of mouse CD4(+) T cells and long-term do nor MUC-matched pig skin graft acceptance were observed. Conclusions. Highly disparate xenogeneic pig skin graft tolerance can be achieved by grafting FP THY alone in anti-CD4 and anti-CD8 mAb-treated ATX B mice, but not in euthymic B6 mice. Additional treat ment of ATX recipient mice with anti-Thy1.2 an NK1.1 mAbs and 3 Gy TBI is not essential for donor pig skin graft tolerance induction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Surg Serv, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Surg Serv, Transplantat Biol Res Ctr,Bone Marrow Transplanta, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011 FU NHLBI NIH HHS [HL186461]; NIAID NIH HHS [P01-AI39755] NR 24 TC 18 Z9 20 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 NOV 27 PY 2001 VL 72 IS 10 BP 1608 EP 1615 DI 10.1097/00007890-200111270-00006 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 500EZ UT WOS:000172614200006 PM 11726819 ER PT J AU Gillespie, PG Albanesi, JP Bahler, M Bement, WM Berg, JS Burgess, DR Burnside, B Cheney, RE Corey, DP Coudrier, E de Lanerolle, P Hammer, JA Hasson, T Holt, JR Hudspeth, AJ Ikebe, M Kendrick-Jones, J Korn, E Li, R Mercer, JA Milligan, RA Mooseker, M Ostap, EM Petit, C Pollard, TD Sellers, JR Soldati, T Titus, MA AF Gillespie, PG Albanesi, JP Bahler, M Bement, WM Berg, JS Burgess, DR Burnside, B Cheney, RE Corey, DP Coudrier, E de Lanerolle, P Hammer, JA Hasson, T Holt, JR Hudspeth, AJ Ikebe, M Kendrick-Jones, J Korn, E Li, R Mercer, JA Milligan, RA Mooseker, M Ostap, EM Petit, C Pollard, TD Sellers, JR Soldati, T Titus, MA TI Myosin-I nomenclature SO JOURNAL OF CELL BIOLOGY LA English DT Editorial Material AB We suggest that the vertebrate myosin-I field adopt a common nomenclature system based on the names adopted by the Human Genome Organization (HUGO). At present, the myosin-I nomenclature is very confusing; not only are several systems in use, but several different genes have been given the same name. Despite their faults, we believe that the names adopted by the HUGO nomenclature group for genome annotation are the best compromise, and we recommend universal adoption. C1 Oregon Hlth Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Univ Munster, Inst Allgemeine Zool & Genet, Munster, Germany. Univ Wisconsin, Dept Zool, Madison, WI 53706 USA. Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. Inst Curie, Unite Mixte Rech 144, Ctr Natl Rech Sci, F-75248 Paris 05, France. Univ Illinois, Dept Physiol, Chicago, IL 60612 USA. Natl Inst Hlth, Lab Cell Biol, Bethesda, MD 20892 USA. Univ Calif San Diego, Sect Cell & Dev Biol, Div Biol, La Jolla, CA 92093 USA. Univ Virginia, Sch Med, Dept Neurosci & Otolaryngol, Charlottesville, VA 22908 USA. Rockefeller Univ, Lab Sensory Neurosci, New York, NY 10021 USA. Rockefeller Univ, Howard Huges Med Inst, New York, NY 10021 USA. Univ Massachusetts, Sch Med, Dept Physiol, Worcester, MA 01655 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Natl Heart & Lung Inst, Lab Cell Biol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. McLaughlin Res Inst, Great Falls, MT 59405 USA. Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Penn Muscle Inst, Philadelphia, PA 19104 USA. Inst Pasteur, CNRS, URA 1968, Unite Genet Deficits Sensoriels, F-75724 Paris 15, France. Natl Heart Lung & Blood Inst, Lab Mol Cardiol, NIH, Bethesda, MD 20892 USA. Imperial Coll Sci Technol & Med, Dept Sci Biol, London SW7 2AZ, England. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. RP Gillespie, PG (reprint author), Oregon Hlth Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97201 USA. RI SOLDATI, Thierry/A-2902-2009; OI SOLDATI, Thierry/0000-0002-2056-7931; Corey, David/0000-0003-4497-6016; Barr-Gillespie, Peter/0000-0002-9787-5860 FU NIDCD NIH HHS [R29 DC003299]; NIGMS NIH HHS [R01 GM057247] NR 1 TC 50 Z9 50 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 26 PY 2001 VL 155 IS 5 BP 703 EP 704 DI 10.1083/jcb.200110032 PG 2 WC Cell Biology SC Cell Biology GA 497MQ UT WOS:000172459900003 PM 11724811 ER PT J AU Pavlov, EV Priault, M Pietkiewicz, D Cheng, EHY Antonsson, B Manon, S Korsmeyer, SJ Mannella, CA Kinnally, KW AF Pavlov, EV Priault, M Pietkiewicz, D Cheng, EHY Antonsson, B Manon, S Korsmeyer, SJ Mannella, CA Kinnally, KW TI A novel, high conductance channel of mitochondria linked to apoptosis in mammalian cells and Bax expression in yeast SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CYTOCHROME-C; OUTER-MEMBRANE; NEUROSPORA-CRASSA; FORMING ACTIVITY; BCL-2; RELEASE; LIPOSOMES; IMPORT; DEATH; PORE AB During apoptosis, proapoptotic factors are released from mitochondria by as yet undefined mechanisms. Patch-clamping of mitochondria and proteoliposomes formed from mitochondrial outer membranes of mammalian (FL5.12) cells has uncovered a novel ion channel whose activity correlates with onset of apoptosis. The pore diameter inferred from the largest conductance state of this channel is similar to4 nm, sufficient to allow diffusion of cytochrome c and even larger proteins. The activity of the channel is affected by Bcl-2 family proteins in a manner consistent with their pro- or antiapoptotic properties. Thus, the channel activity correlates with presence of proapoptotic Bax in the mitochondrial outer membrane and is absent in mitochondria from cells overexpressing antiapoptotic Bcl-2. Also, a similar channel activity is found in mitochondrial outer membranes of yeast expressing human Bax. These findings implicate this channel, named mitochondrial apoptosis-induced channel, as a candidate for the outer-membrane pore through which cytochrome c and possibly other factors exit mitochondria during apoptosis. C1 NYU, Coll Dent, Div Basic Sci, New York, NY 10010 USA. CNRS, Inst Biochim & Genet Cellulaires, F-33077 Bordeaux, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Med, Boston, MA 02115 USA. Serono Int SA, Serono Pharmaceut Res Inst, CH-1228 Plan Les Ouates, Switzerland. New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12203 USA. RP Kinnally, KW (reprint author), NYU, Coll Dent, Div Basic Sci, 345 E 24th St, New York, NY 10010 USA. RI Manon, Stephen/C-7088-2017 FU NIGMS NIH HHS [GM57249, R01 GM057249] NR 42 TC 200 Z9 210 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 26 PY 2001 VL 155 IS 5 BP 725 EP 731 DI 10.1083/jcb.200107057 PG 7 WC Cell Biology SC Cell Biology GA 497MQ UT WOS:000172459900007 PM 11724814 ER PT J AU van der Lely, AJ Hutson, RK Trainer, PJ Besser, GM Barkan, AL Katznelson, L Klibanski, A Herman-Bonert, V Melmed, S Vance, ML Freda, PU Stewart, PM Friend, KE Clemmons, DR Johannsson, G Stavrou, S Cook, DM Phillips, LS Strasburger, CJ Hacker, S Zib, KA Davis, RJ Scarlett, JA Thorner, M AF van der Lely, AJ Hutson, RK Trainer, PJ Besser, GM Barkan, AL Katznelson, L Klibanski, A Herman-Bonert, V Melmed, S Vance, ML Freda, PU Stewart, PM Friend, KE Clemmons, DR Johannsson, G Stavrou, S Cook, DM Phillips, LS Strasburger, CJ Hacker, S Zib, KA Davis, RJ Scarlett, JA Thorner, M TI Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist SO LANCET LA English DT Article ID TRANSSPHENOIDAL SURGERY; GH ANTAGONIST; OCTREOTIDE; THERAPY; MICE AB Background Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulinlike growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days. Methods Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis. Findings Mean serum IGF-1 concentrations fell by at least 50%: 467 mug/L (SE 24), 526 mug/L (29), and 523 mug/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 g/L (2.1), 12.5 mug/L (3.0), and 14.2 mug/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 g/L (2.5) at baseline, rose to 15.2 mug/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mug/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353). Interpretation Pegvisomant is an effective medical treatment for acromegaly. C1 Erasmus Med Ctr Rotterdam, NL-3015 GD Rotterdam, Netherlands. Univ Tennessee, Knoxville, TN USA. Christie Hosp, Manchester, Lancs, England. St Bartholomews Hosp, London, England. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Queen Elizabeth Hosp, Birmingham B15 2TH, W Midlands, England. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. NYU, Med Ctr, New York, NY 10016 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Munich, Klinikum Innenstadt, D-8000 Munich, Germany. StatWorks Inc, Chapel Hill, NC USA. Sensus Drug Dev Corp, Austin, TX USA. RP van der Lely, AJ (reprint author), Erasmus Med Ctr Rotterdam, 40 Dr Molewaterpl, NL-3015 GD Rotterdam, Netherlands. OI Trainer, Peter/0000-0003-0146-3835 NR 27 TC 338 Z9 344 U1 0 U2 11 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 24 PY 2001 VL 358 IS 9295 BP 1754 EP 1759 DI 10.1016/S0140-6736(01)06844-1 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 496FG UT WOS:000172385100009 PM 11734231 ER PT J AU Joffe, S Cook, EF Cleary, PD Clark, JW Weeks, JC AF Joffe, S Cook, EF Cleary, PD Clark, JW Weeks, JC TI Quality of informed consent in cancer clinical trials: a cross-sectional survey SO LANCET LA English DT Article ID INFORMATION; PERCEPTIONS AB Background Investigators have to obtain informed consent before enrolling participants in clinical trials. We wanted to measure the quality of understanding among participants in clinical trials of cancer therapies, to identify correlates of increased understanding, and to assess providers' beliefs about clinical research. We also sought evidence of therapeutic misconceptions in participants and providers. Methods We sent a standard questionnaire to 287 adult patients with cancer who had recently enrolled in a clinical trial at one of three affiliated institutions, and surveyed the provider who obtained each patient's consent. Findings 207 of 287 (72%) patients responded. 90% (186) of these respondents were satisfied with the informed consent process and most considered themselves to be well informed. Nevertheless, many did not recognise nonstandard treatment (74%), the potential for incremental risk from participation (63%), the unproven nature of the treatment (70%), the uncertainty of benefits to self (29%), or that trials are done mainly to benefit future patients (25%). In multivariate analysis, increased knowledge was associated with college education, speaking only English at home, use of the US National Cancer Institute consent form template, not signing the consent form at initial discussion, presence of a nurse, and careful reading of the consent form. Only 28 of 61 providers (46%) recognised that the main reason for clinical trials is benefit to future patients. Interpretation Misconceptions about cancer clinical trials are frequent among trial participants, and physician/investigators might share some of these misconceptions. Efforts to educate providers and participants about the underlying goals of clinical trials are needed. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Paediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Weeks, JC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Paediat Oncol, 454 BRK Suite 21,44 Binney St, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 FU AHRQ HHS [T32 HS00063] NR 31 TC 332 Z9 341 U1 3 U2 15 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 24 PY 2001 VL 358 IS 9295 BP 1772 EP 1777 DI 10.1016/S0140-6736(01)06805-2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 496FG UT WOS:000172385100013 PM 11734235 ER PT J AU Kamata, T Tieu, KK Irie, A Springer, TA Takada, Y AF Kamata, T Tieu, KK Irie, A Springer, TA Takada, Y TI Amino acid residues in the alpha(IIb) subunit that are critical for ligand binding to integrin alpha(IIb)beta(3) are clustered in the beta-propeller model SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLATELET GLYCOPROTEIN-IIB; MONOCLONAL-ANTIBODY; GPIIB-IIIA; ALPHA-IIB-BETA-3 INTEGRIN; GLANZMANN THROMBASTHENIA; FIBRINOGEN BINDING; IIB/IIIA COMPLEX; DOMAIN; SITE; RECOGNITION AB Several distinct regions of the integrin am, subunit have been implicated in ligand binding. To localize the ligand binding sites in alpha (IIb), we swapped all 27 predicted loops with the corresponding sequences of alpha (4) or alpha (5). 19 of the 27 swapping mutations had no effect on binding to both fibrinogen and ligand-mimetic antibodies (e.g. LJ-CP3), suggesting that these regions do not contain major ligand binding sites. In contrast, swapping the remaining 8 predicted loops completely blocked ligand binding. Ala scanning mutagenesis of these critical predicted loops identified more than 30 discontinuous residues in repeats 2-4 and at the boundary between repeats 4 and 5 as critical for ligand binding. Interestingly, these residues are clustered in the predicted beta -propeller model consistent with this model. Most of the critical residues are located at the edge of the upper face of the propeller, and several critical residues are located on the side of the propeller domain. None of the predicted loops in repeats 1, 6, and 7, and none of the four putative Ca2+ binding predicted loops on the lower surface of the beta -propeller were important for ligand binding. The results map an important ligand binding interface at the edge of the top and on the side of the beta -propeller toroid, centering on repeat 3. C1 Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Kamata, T (reprint author), Scripps Res Inst, Dept Cell Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI takada, yoshikazu/0000-0001-5481-9589 FU NHLBI NIH HHS [HL48675]; NIGMS NIH HHS [GM49899] NR 58 TC 62 Z9 62 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 NOV 23 PY 2001 VL 276 IS 47 BP 44275 EP 44283 DI 10.1074/jbc.M107021200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 494QQ UT WOS:000172297700100 PM 11557768 ER PT J AU Nizet, V Ohtake, T Lauth, X Trowbridge, J Rudisill, J Dorschner, RA Pestonjamasp, V Piraino, J Huttner, K Gallo, RL AF Nizet, V Ohtake, T Lauth, X Trowbridge, J Rudisill, J Dorschner, RA Pestonjamasp, V Piraino, J Huttner, K Gallo, RL TI Innate antimicrobial peptide protects the skin from invasive bacterial infection SO NATURE LA English DT Article ID ANTIBACTERIAL PEPTIDE; CYSTIC-FIBROSIS; STREPTOLYSIN-S; IDENTIFICATION; RESISTANCE; VIRULENCE; IMMUNITY; NEUTROPHILS; DEFENSINS; PRECURSOR AB In mammals, several gene families encode peptides with antibacterial activity, such as the beta -defensins and cathelicidins(1-3). These peptides are expressed on epithelial surfaces and in neutrophils, and have been proposed to provide a first line of defence against infection by acting as 'natural antibiotics'(4,5). The protective effect of antimicrobial peptides is brought into question by observations that several of these peptides are easily inactivated(6-8) and have diverse cellular effects that are distinct from antimicrobial activity demonstrated in vitro(9-13). To investigate the function of a specific antimicrobial peptide in a mouse model of cutaneous infection, we applied a combined mammalian and bacterial genetic approach to the cathelicidin antimicrobial gene family(14). The mature human (LL-37)(15) and mouse (CRAMP)(16) peptides are encoded by similar genes (CAMP and Cnlp, respectively), and have similar alpha -helical structures, spectra of antimicrobial activity and tissue distribution. Here we show that cathelicidins are an important native component of innate host defence in mice and provide protection against necrotic skin infection caused by Group A Streptococcus (GAS). C1 Univ Calif San Diego, Dept Pediat, San Diego, CA 92161 USA. Univ Calif San Diego, Div Dermatol, San Diego, CA 92161 USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA 92161 USA. Massachusetts Gen Hosp, Div Neonatol, Boston, MA 02114 USA. RP Gallo, RL (reprint author), Univ Calif San Diego, Dept Pediat, San Diego, CA 92161 USA. RI Gallo, Richard/A-8931-2009; OI Dorschner, Robert/0000-0002-4773-4461 NR 30 TC 762 Z9 790 U1 7 U2 62 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 22 PY 2001 VL 414 IS 6862 BP 454 EP 457 DI 10.1038/35106587 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 494UP UT WOS:000172304500045 PM 11719807 ER PT J AU Brasher, BB Roumiantsev, S Van Etten, RA AF Brasher, BB Roumiantsev, S Van Etten, RA TI Mutational analysis of the regulatory function of the c-Abl Src homology 3 domain SO ONCOGENE LA English DT Article DE abelson; tyrosine kinase; retrovirus; chronic myeloid leukemia ID TYROSINE KINASE-ACTIVITY; PROLINE-RICH LIGANDS; SH3 DOMAIN; TRANSFORMING ACTIVITY; PROTEIN-BINDING; GENE-PRODUCT; CELL-LINE; ACTIVATION; ABILITY; LYMPHOCYTES AB The catalytic activity of the c-Abl tyrosine kinase is tightly regulated by its Src homology 3 (SH3) domain through a complex mechanism that may involve intramolecular binding to Pro242 in the linker region between the SH2 and catalytic domains as well as interactions with a trans-inhibitor. We analysed the effect of mutation or replacement of SH3 on c-Abl tyrosine kinase activity and transformation. Random mutagenesis of SH3 identified several novel point mutations that dysregulated c-Abl kinase activity in vivo, but the RT loop was insensitive to mutational activation. Activating SH3 mutations abolished binding of proline-rich SH3 ligands in vitro, while mutations at Ser140 in the connector between the SH3 and SH2 domains activated Abl kinase activity in vivo and in vitro but did not impair SH3 ligand-binding. Abl was regulated efficiently when its SH3 domain was replaced with a heterologous SH3 from c-Src that binds a different spectrum of proline-rich ligands, but not by substitution of a modular WW domain with similar ligand-binding specificity. These results suggest that the SH3 domain regulates Abl principally by binding to the atypical intramolecular ligand Pro242 rather than a canonical PxxP ligand. Coordination between the SH3 and SH2 domains mediated by the connector region may be required for regulation of Abl even in the absence of SH2 ligand binding. C1 Enanta Pharmaceut, Watertown, MA 02472 USA. Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, Boston, MA 02114 USA. Enanta Pharmaceut, Watertown, MA 02472 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Dept Genet, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02114 USA. FU NCI NIH HHS [CA72465] NR 44 TC 36 Z9 37 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 22 PY 2001 VL 20 IS 53 BP 7744 EP 7752 DI 10.1038/sj.onc.1204978 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 492HE UT WOS:000172161700005 PM 11753652 ER PT J AU Morrow, DA Cannon, CP Rifai, N Frey, MJ Vicari, R Lakkis, N Robertson, DH Hille, DA DeLucca, PT DiBattiste, PM Demopoulos, LA Weintraub, WS Braunwald, E AF Morrow, DA Cannon, CP Rifai, N Frey, MJ Vicari, R Lakkis, N Robertson, DH Hille, DA DeLucca, PT DiBattiste, PM Demopoulos, LA Weintraub, WS Braunwald, E CA TACTICS-TIMI-18 Investigators TI Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction - Results from a randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE CORONARY SYNDROMES; ARTERY DISEASE; STRATIFICATION; EFFICACY; TIROFIBAN AB Context Cardiac troponins I (cTnI) and T (cTnT) are useful for assessing prognosis in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the use of cardiac troponins for predicting benefit of an invasive vs conservative strategy in this patient population is not clear. Objective To prospectively test whether an early invasive strategy provides greater benefit than a conservative strategy in acute coronary syndrome patients with elevated baseline troponin levels. Design Prospective, randomized trial conducted from December 1997 to June 2000. Setting One hundred sixty-nine community and tertiary care hospitals in 9 countries. Participants A total of 2220 patients with acute coronary syndrome were enrolled. Baseline troponin level data were available for analysis in 1821, and 1780 completed the 6-month follow-up. Interventions Patients were randomly assigned to receive (1) an early invasive strategy of coronary angiography between 4 and 48 hours after randomization and revascularization when feasible based on coronary anatomy (n = 1114) or (2) a conservative strategy of medical treatment and, if stable, predischarge exercise tolerance testing (n = 1106). Conservative strategy patients underwent coronary angiography and revascularization only if they manifested recurrent ischemia at rest or on provocative testing. Main Outcome Measure Composite end point of death, AAI, or rehospitalization for acute coronary syndrome at 6 months. Results Patients with a cTnI level of 0.1 ng/mL or more (n = 1087) experienced a significant reduction in the primary end point with the invasive vs conservative strategy (15.3% vs 25.0%; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.40-0.73). Patients with cTnI levels of less than 0.1 ng/mL had no detectable benefit from early invasive management (16.0% vs 12.4%; OR, 1.4; 95% CI, 0.89-2.05; P<.001 for interaction). The benefit of invasive vs conservative management through 30 days was evident even among patients with low-level (0.1-0.4 ng/mL) cTnI elevation (4.4% vs 16.5%; OR, 0.24; 95% Cl, 0.08-0.69). Directionally similar results were observed with cTnT. Conclusion In patients with clinically documented acute coronary syndrome who are treated with glycoprotein IIb/IIIa inhibitors, even small elevations in cTnI and cTnT identify high-risk patients who derive a large clinical benefit from an early invasive strategy. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Emory Univ, Atlanta, GA 30322 USA. Merck & Co Inc, W Point, PA USA. Heart Ctr Sarasota, Sarasota, FL USA. Holmes Reg Med Ctr, Melbourne, FL USA. Baylor Coll Med, Houston, TX 77030 USA. Childrens Hosp, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 21 TC 411 Z9 428 U1 0 U2 4 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 NOV 21 PY 2001 VL 286 IS 19 BP 2405 EP 2412 DI 10.1001/jama.286.19.2405 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 494DH UT WOS:000172266100019 PM 11712935 ER PT J AU Ravenel, JD Broman, KW Perlman, EJ Niemitz, EL Jayawardena, TM Bell, DW Haber, DA Uejima, H Feinberg, AP AF Ravenel, JD Broman, KW Perlman, EJ Niemitz, EL Jayawardena, TM Bell, DW Haber, DA Uejima, H Feinberg, AP TI Loss of imprinting of insulin-like growth factor-II (IGF2) gene in distinguishing specific biologic subtypes of Wilms tumor SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; HUMAN-BREAST CANCER; HUMAN NEUROBLASTOMA; EXPRESSION; H19; HETEROZYGOSITY; CHROMOSOME-11; CELLS; RHABDOMYOSARCOMA; HEPATOBLASTOMA AB Background: Loss of imprinting (LOI) of the insulin-like growth factor-II (IGF2) gene, an epigenetic alteration associated with expression of the normally silent maternal allele, was observed first in Wilms tumor. Although LOI has subsequently been detected in most adult tumors, the biologic role of LOI in cancer remains obscure. We analyzed the imprinting status of Wilms tumors with respect to pathologic subtype, stage, and patient's age at diagnosis and examined the expression of genes potentially affected by LOI. Methods: Of 60 Wilms tumors examined, 25 were informative for an ApaI polymorphism in the IGF2 gene, allowing analysis of allele-specific gene expression, and could be classified by pathologic subtype. Gene expression was measured quantitatively by real-time polymerase chain reaction, and pathologic analysis was blinded for genetic status. All statistical tests were two-sided. Results: We observed LOI of IGF2 in nine (90%) of 10 Wilms tumors classified as having a pathologic subtype associated with a later stage of renal development and in only one (6.7%) of 15 Wilms tumors with a pathologic subtype associated with an earlier stage of renal development (P < .001). LOI was associated with a 2.2-fold increase (95% confidence interval [CI] = 1.6-fold to 3.1-fold) in IGF2 expression (P<.001). Children whose Wilms tumors displayed LOI of IGF2 were statistically significantly older at diagnosis (median = 65 months; interquartile range [IQR] = 47-83 months) than children whose tumors displayed normal imprinting (median = 24 months; IQR = 13-35 months; P<.001). Conclusions: These data demonstrate a clear relationship between LOI and altered expression of IGF2 in Wilms tumors and provide a molecular basis for understanding the divergent pathogenesis of this cancer. Analysis of LOI could provide a valuable molecular tool for the classification of Films tumor. C1 Johns Hopkins Univ, Sch Med, Inst Med Genet, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Feinberg, AP (reprint author), Johns Hopkins Univ, Sch Med, Inst Med Genet, Dept Pathol, Ross 1064,720 Rutland Ave, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA65145] NR 49 TC 115 Z9 119 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 NOV 21 PY 2001 VL 93 IS 22 BP 1698 EP 1703 DI 10.1093/jnci/93.22.1698 PG 6 WC Oncology SC Oncology GA 494MX UT WOS:000172287400009 PM 11717330 ER PT J AU Arozullah, AM Khuri, SF Henderson, WG Daley, J AF Arozullah, AM Khuri, SF Henderson, WG Daley, J CA Natl Vet Affairs Surgical Quality TI Development and validation of a multifactorial risk index for predicting postoperative pneumonia after major noncardiac surgery SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID AFFAIRS SURGICAL RISK; PULMONARY COMPLICATIONS; ABDOMINAL-SURGERY; MULTIVARIATE-ANALYSIS; ADJUSTMENT; QUALITY; DISEASE; CARE; MANAGEMENT; MORTALITY AB Background: Pneumonia is a common postoperative complication associated with substantial morbidity and mortality. Objective: To develop and validate a preoperative risk index for predicting postoperative pneumonia. Design: Prospective cohort study with outcome assessment based on chart review. Setting: 100 Veterans Affairs Medical Centers performing major surgery. Patients: The risk index was developed by using data on 160 805 patients undergoing major noncardiac surgery between I September 1997 and 31 August 1999 and was validated by using data on 155 266 patients undergoing surgery between 1 September 1995 and 31 August 1997. Patients with preoperative pneumonia, ventilator dependence, and pneumonia that developed after postoperative respiratory failure were excluded. Measurements: Postoperative pneumonia was defined by using the Centers for Disease Control and Prevention definition of nosocomial pneumonia. Results: A total of 2466 patients (1.5%) developed pneumonia, and the 30-day postoperative mortality rate was 21%. A postoperative pneumonia risk index was developed that included type of surgery (abdominal aortic aneurysm repair, thoracic, upper abdominal, neck, vascular, and neurosurgery), age, functional status, weight loss, chronic obstructive pulmonary disease, general anesthesia, impaired sensorium, cerebral vascular accident, blood urea nitrogen level, transfusion, emergency surgery, long-term steroid use, smoking, and alcohol use. Patients were divided into five risk classes by using risk index scores. Pneumonia rates were 0.2% among those with 0 to 15 risk points, 1.2% for those with 16 to 25 risk points, 4.0% for those with 26 to 40 risk points, 9.4% for those with 41 to 55 risk points, and 15.3% for those with more than 55 risk points. The C-statistic was 0.805 for the development cohort and 0.817 for the validation cohort. Conclusions: The postoperative pneumonia risk index identifies patients at risk for postoperative pneumonia and may be useful in guiding perioperative respiratory care. C1 Univ Illinois, Coll Med, Gen Internal Med Sect, Vet Affairs Chicago Healthcare Syst,Westside Div, Chicago, IL 60612 USA. Vet Affairs Boston Healthcare Syst, West Roxbury, MA USA. Hines Vet Affairs Cooperat Studies Program Coordi, Hines, IL USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners Hlth Care Syst, Ctr Hlth Syst Design & Evaluat, Inst Hlth Policy, Boston, MA 02114 USA. RP Arozullah, AM (reprint author), Univ Illinois, Coll Med, Gen Internal Med Sect, Vet Affairs Chicago Healthcare Syst,Westside Div, M-C 787,840 S Wood St,Room 440-M, Chicago, IL 60612 USA. NR 32 TC 276 Z9 289 U1 0 U2 5 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 NOV 20 PY 2001 VL 135 IS 10 BP 847 EP 857 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 494DY UT WOS:000172267500001 PM 11712875 ER PT J AU Lawrence, VA AF Lawrence, VA TI Predicting postoperative pulmonary complications: The sleeping giant stirs SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID NONCARDIAC SURGERY; RISK; INDEX; MEN C1 Univ Texas, Hlth Sci Ctr, Audie Murphy Div, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Lawrence, VA (reprint author), Univ Texas, Dept Med, Div Gen Med, Hlth Sci Ctr, 7703 Floyd Curl Dr,Mail Code 7879, San Antonio, TX 78229 USA. NR 11 TC 7 Z9 7 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 NOV 20 PY 2001 VL 135 IS 10 BP 919 EP 921 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 494DY UT WOS:000172267500008 PM 11712882 ER PT J AU de Chateau, M Chen, SQ Salas, A Springer, TA AF de Chateau, M Chen, SQ Salas, A Springer, TA TI Kinetic and mechanical basis of rolling through an integrin and novel Ca2+-dependent rolling and Mg2+-dependent firm adhesion modalities for the alpha 4 beta 7-MAdCAM-1 interaction SO BIOCHEMISTRY LA English DT Article ID BETA-PROPELLER DOMAIN; FUNCTION-ASSOCIATED ANTIGEN-1; DIVALENT-CATION REGULATION; L-SELECTIN; CELL-ADHESION; LIGAND-BINDING; PHYSIOLOGICAL FLOW; HYDRODYNAMIC FLOW; SHEAR THRESHOLD; ALPHA-SUBUNITS AB We studied interactions in shear flow of cells bearing integrins alpha4 beta1 or alpha4 beta7 with VCAM-1 and MAdCAM-1 substrates in different divalent cations. Interestingly, Ca2+ was essential for tethering in flow and rolling, interactions through both alpha4 integrins. Mg2+ promoted firm adhesion of alpha4 beta7-expressing cells on MAdCAM-l but with much lower tetherina efficiency in shear flow. The k,,ff' of 1.28 s-1 and L resistance of the receptor-ligand bond to force (estimated as a bond interaction distance or Gr) for transient tethers on MAdCAM-1 were similar to values for E- and P-selectins. By contrast to results in Ca2+ or Ca2+ + Mg2+ in Mg2+ the alpha4 beta7-MAdCAM-1 k(off)degrees decreased 20-fold to 0.046 s(-1), and the bond was weaker, providing an explanation for the finding of firm adhesion under these conditions. Shear enhanced tethering to MAdCAM-1, thereby contributing to the stability of rolling. Comparisons to selectins demonstrate that the kinetic and mechanical properties of the alpha4 beta7 integrin are well suited to its intermediate position in adhesion cascades, in which it bridges rapid rolling through selectins to firm adhesion through beta2 integrins. C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. OI Salas, Azucena/0000-0003-4572-2907 FU NHLBI NIH HHS [HL48675] NR 64 TC 32 Z9 32 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 20 PY 2001 VL 40 IS 46 BP 13972 EP 13979 DI 10.1021/bi011582f PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 493VQ UT WOS:000172244500026 PM 11705388 ER PT J AU Vanduffel, W Fize, D Mandeville, JB Nelissen, K Van Hecke, P Rosen, BR Tootell, RBH Orban, GA AF Vanduffel, W Fize, D Mandeville, JB Nelissen, K Van Hecke, P Rosen, BR Tootell, RBH Orban, GA TI Visual motion processing investigated using contrast agent-enhanced fMRI in awake behaving monkeys SO NEURON LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; CEREBRAL BLOOD-VOLUME; FRONTAL EYE FIELD; AREA MT; MACAQUE MONKEY; EXTRASTRIATE CORTEX; RESPONSE PROPERTIES; FUNCTIONAL-ANALYSIS; INTRAPARIETAL AREA; HUMAN BRAIN AB To reduce the information gap between human neuroimaging and macaque physiology and anatomy, we mapped fMRI signals produced by moving and stationary stimuli (random dots or lines) in fixating monkeys. Functional sensitivity was increased by a factor of similar to5 relative to the BOLD technique by injecting a contrast agent (monocrystalline iron oxide nanoparticle [MION]). Areas identified as motion sensitive included V2, V3, MT/V5, vMST, FST, VIP, and FEF (with moving dots), as well as V4, TE, LIP, and PIP (with random lines). These regions sensitive for moving dots are largely in agreement with monkey single unit data and (except for V3A) with human fMRI results. Moving lines activate some regions that have not been previously implicated in motion processing. Overall, the results clarify the relationship between the motion pathway and the dorsal stream in primates. C1 Katholieke Univ Leuven, Neuro & Psychofysiol Lab, Louvain, Belgium. UZ Gasthuisberg, Afdeling Radiol, B-3000 Louvain, Belgium. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Vanduffel, W (reprint author), Katholieke Univ Leuven, Neuro & Psychofysiol Lab, Campus Gasthuisberg,Herestr 49, Louvain, Belgium. RI Fize, Denis/F-4525-2011 NR 61 TC 250 Z9 255 U1 5 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 20 PY 2001 VL 32 IS 4 BP 565 EP 577 DI 10.1016/S0896-6273(01)00502-5 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 495WT UT WOS:000172363900005 PM 11719199 ER PT J AU Culham, JC Cavanagh, P Kanwisher, NG AF Culham, JC Cavanagh, P Kanwisher, NG TI Attention response functions: Characterizing brain areas using fMRI activation during parametric variations of attentional load SO NEURON LA English DT Article ID FRONTAL EYE-FIELD; POSITRON EMISSION TOMOGRAPHY; HUMAN VISUAL-CORTEX; SPATIAL ATTENTION; WORKING-MEMORY; CEREBRAL-CORTEX; SINGLE NEURONS; SACCADES; MOVEMENTS; MODULATION AB We derived attention response functions for different cortical areas by plotting neural activity (measured by fMRI) as a function of attentional load in a visual tracking task. In many parietal and frontal cortical areas, activation increased with load over the entire range of loads tested, suggesting that these areas are directly involved in attentional processes. However, in other areas (FEF and parietal area 7), strong activation was observed even at the lowest attentional load (compared to a passive baseline using identical stimuli), but little or no additional activation was seen with increasing load. These latter areas appear to play a different role, perhaps supporting task-relevant functions that do not vary with load, such as the suppression of eye movements. C1 Univ Western Ontario, Dept Psychol, London, ON N6A 5C2, Canada. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Culham, JC (reprint author), Univ Western Ontario, Dept Psychol, London, ON N6A 5C2, Canada. RI Culham, Jody/A-9863-2013 OI Culham, Jody/0000-0003-0754-2999 FU NIMH NIH HHS [MH56037] NR 53 TC 191 Z9 195 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 20 PY 2001 VL 32 IS 4 BP 737 EP 745 DI 10.1016/S0896-6273(01)00499-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 495WT UT WOS:000172363900018 PM 11719212 ER PT J AU Bhattacharjee, A Richards, WG Staunton, J Li, C Monti, S Vasa, P Ladd, C Beheshti, J Bueno, R Gillette, M Loda, M Weber, G Mark, EJ Lander, ES Wong, W Johnson, BE Golub, TR Sugarbaker, DJ Meyerson, M AF Bhattacharjee, A Richards, WG Staunton, J Li, C Monti, S Vasa, P Ladd, C Beheshti, J Bueno, R Gillette, M Loda, M Weber, G Mark, EJ Lander, ES Wong, W Johnson, BE Golub, TR Sugarbaker, DJ Meyerson, M TI Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PULMONARY ADENOCARCINOMA; MOLECULAR CLASSIFICATION; OLIGONUCLEOTIDE ARRAYS; CANCER; PATTERNS; TUMORS; DIFFERENTIATION; MICROARRAY; FEATURES; SYSTEM AB We have generated a molecular taxonomy of lung carcinoma, the leading cause of cancer death in the United States and worldwide. Using oligonucleotide microarrays, we analyzed mRNA expression levels corresponding to 12,600 transcript sequences in 186 lung tumor samples, including 139 adenocarcinomas resected from the lung. Hierarchical and probabilistic clustering of expression data defined distinct subclasses of lung adenocarcinoma. Among these were tumors with high relative expression of neuroendocrine genes and of type II pneumocyte genes, respectively. Retrospective analysis revealed a less favorable outcome for the adenocarcinomas with neuroendocrine gene expression. The diagnostic potential of expression profiling is emphasized by its ability to discriminate primary lung adenocarcinomas from metastases of extra-pulmonary origin. These results suggest that integration of expression profile data with clinical parameters could aid in diagnosis of lung cancer patients. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Golub, TR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Meyerson, Matthew/E-7123-2012; OI Weber, Griffin/0000-0002-2597-881X FU NCI NIH HHS [U01 CA084995, U01 CA84995] NR 34 TC 1474 Z9 1528 U1 5 U2 40 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2001 VL 98 IS 24 BP 13790 EP 13795 DI 10.1073/pnas.191502998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100059 PM 11707567 ER PT J AU Naumov, YN Bahjat, KS Gausling, R Abraham, R Exley, MA Koezuka, Y Balk, SB Strominger, JL Clare-Salzer, M Wilson, SB AF Naumov, YN Bahjat, KS Gausling, R Abraham, R Exley, MA Koezuka, Y Balk, SB Strominger, JL Clare-Salzer, M Wilson, SB TI Activation of CD1d-restricted T cells protects NOD mice from developing diabetes by regulating dendritic cell subsets SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID V(ALPHA)14 NKT CELLS; HELPER-CELLS; IN-VIVO; DIFFERENTIATION; EXPRESSION; TOLERANCE; DISEASE; DEFICIENCY; ANTIGENS; MOUSE AB CD1d-restricted invariant NKT (iNKT) cells are immunoregulatory cells whose loss exacerbates diabetes in nonobese diabetic (NOD) female mice. Here, we show that the relative numbers of iNKT cells from the pancreatic islets of NOD mice decrease at the time of conversion from peri-insulitis to invasive insulitis and diabetes. Conversely, NOD male mice who have a low incidence of diabetes showed an increased frequency of iNKT cells. Moreover, administration of alpha -galactosylceramide, a potent activating ligand presented by CD1d, ameliorated the development of diabetes in NOD female mice and resulted in the accumulation of iNKT cells and myeloid dendritic cells (DC) in pancreatic lymph nodes (PLN), but not in inguinal lymph nodes. Strikingly, injection of NOD female mice with myeloid DC isolated from the PLN, but not those from the inguinal lymph nodes, completely prevented diabetes. Thus, the immunoregulatory role of iNKT cells is manifested by the recruitment of tolerogenic myeloid DC to the PLN and the inhibition of ongoing autoimmune inflammation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. Mayo Clin, Dept Immunol, Rochester, MN 55905 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. Kirin Brewery Co Ltd, Pharmaceut Res Lab, Gunma, Japan. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Clare-Salzer, M (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [R35 CA47554]; NIAID NIH HHS [R01 AI45051, R01 AI045051]; PHS HHS [P01 142288] NR 43 TC 232 Z9 237 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 NOV 20 PY 2001 VL 98 IS 24 BP 13838 EP 13843 DI 10.1073/pnas.251531798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100067 PM 11707602 ER PT J AU Nathoo, AN Moeller, RA Westlund, BA Hart, AC AF Nathoo, AN Moeller, RA Westlund, BA Hart, AC TI Identification of neuropeptide-like protein gene families in Caenorhabditis elegans and other species SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FMRFAMIDE-LIKE PEPTIDES; C-ELEGANS; NERVOUS-SYSTEM; MOLECULAR-CLONING; HYPOCRETIN OREXIN; MOTOR NEURON; APLYSIA; MYOMODULIN; RECEPTOR; EXPRESSION AB Neuropeptides play critical roles in synaptic signaling in all nervous systems. Unlike classical neurotransmitters, peptidergic neurotransmitters are encoded as preproproteins that are posttranslationally processed to yield bioactive neuropeptides. To identify novel peptidergic neurotransmitters, the Caenorhabditis elegans genome was searched for predicted proteins with the structural hallmarks of neuropeptide preproproteins. Thirty-two C elegans neuropeptide-like protein (nlp) genes were identified. The nlp genes define at least 11 families of putative neuropeptides with unique motifs; similar expressed sequence tags were identified in other invertebrate species for all 11 families. Six of these families are defined by putative bioactive motifs (FAFA, GGxYamide, MRxamide, LQFamide, LxDxamide, and GGARAF); the remaining five families are related to allatostatin, myomodulin, buccalin/drosulfakinin, orcokinin, and APGWamide neuropeptides (MGL/Famide, FRPamide, MSFamide, GFxGF, and YGGWamide families, respectively). Most C elegans nlp gene expression is in neurons. The C elegans nlp genes and similar genes encoding putative neuropeptides in other species are likely to play diverse roles in nervous system function. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP Massachusetts Gen Hosp, Ctr Canc, 149-7202 13th St, Charlestown, MA 02129 USA. EM hart@helix.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM057918-05, R01 GM057918] NR 50 TC 205 Z9 244 U1 2 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 NOV 20 PY 2001 VL 98 IS 24 BP 14000 EP 14005 DI 10.1073/pnas.241231298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100095 PM 11717458 ER PT J AU Kanai, AJ Pearce, LL Clemens, PR Birder, LA VanBibber, MM Choi, SY de Groat, WC Peterson, J AF Kanai, AJ Pearce, LL Clemens, PR Birder, LA VanBibber, MM Choi, SY de Groat, WC Peterson, J TI Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cardiomyocytes; cytochrome oxidase; oxidative phosphorylation; respiration; chronoamperometry ID CYTOCHROME-C-OXIDASE; DUCHENNE MUSCULAR-DYSTROPHY; MUSCLE FIBERS; RAT-LIVER; RESPIRATION; PEROXYNITRITE; MODULATION; SKELETAL; RELEASE; PURIFICATION AB Mitochondrial nitric oxide synthase (mtNOS), its cellular NOS isoform, and the effects of mitochondrially produced NO on bioenergetics have been controversial since mtNOS was first proposed in 1995. Here we functionally demonstrate the presence of a NOS in cardiac mitochondria. This was accomplished by direct porphyrinic microsensor measurement of Ca2+-dependent NO production in individual mitochondria isolated from wild-type mouse hearts. This NO production could be inhibited by NOS antagonists or protonophore collapse of the mitochondrial membrane potential. The similarity of mtNOS to the neuronal isoform was deduced by the absence of NO production in the mitochondria of knockout mice for the neuronal, but not the endothelial or inducible, isoforms. The effects of mitochondrially produced NO on bioenergetics were studied in intact cardiomyocytes isolated from dystrophin-deficient (mdx) mice. mdx cardiomyocytes are also deficient in cellular endothelial NOS, but overexpress mtNOS, which allowed us to study the mitochondrial enzyme in intact cells free of its cytosolic counterpart. In these cardiomyocytes, which produce NO beat-to-beat, inhibition of mtNOS increased myocyte shortening by approximately one-fourth. Beat-to-beat NO production and altered shortening by NOS inhibition were not observed in wildtype cells. A plausible mechanism for the reversible NO inhibition of contractility in these cells involves the reaction of NO with cytochrome c oxidase. This suggests a modulatory role for NO in oxidative phosphorylation and, in turn, myocardial contractility. C1 Univ Pittsburgh, Dept Med, Lab Epithelial Cell Biol, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Healthcare Syst, Serv Neurol, Pittsburgh, PA 15240 USA. Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. RP Kanai, AJ (reprint author), Univ Pittsburgh, Dept Med, Lab Epithelial Cell Biol, Renal Electrolyte Div, Pittsburgh, PA 15261 USA. OI Pearce, Linda/0000-0002-0940-965X; Peterson, James/0000-0002-7300-5887 FU NHLBI NIH HHS [HL 61411, R01 HL061411]; NIDDK NIH HHS [DK 54824, R01 DK054824, R37 DK054824] NR 51 TC 266 Z9 273 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 20 PY 2001 VL 98 IS 24 BP 14126 EP 14131 DI 10.1073/pnas.241380298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 495EW UT WOS:000172328100117 PM 11717466 ER PT J AU Haile, D Liu, XB Ghio, A Quinones, M Yang, FM AF Haile, D Liu, XB Ghio, A Quinones, M Yang, FM TI Regulation of reticuloendothelial cell iron transporter, SLC11A3, by inflammation. SO BLOOD LA English DT Meeting Abstract C1 Audie L Murphy Vet Admin Hosp, S Texas Vet Hlth Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. US EPA, Natl Hlth & Environm Effects Res Lab, Chapel Hill, NC USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1 BP 4A EP 4A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100002 ER PT J AU Avigan, D Gong, JL Uhl, L Wu, ZK Vasir, D Smith, T Borges, V Atkins, M Stone, C Giallombardo, N Schadt, K Tetreault, JC Kufe, D AF Avigan, D Gong, JL Uhl, L Wu, ZK Vasir, D Smith, T Borges, V Atkins, M Stone, C Giallombardo, N Schadt, K Tetreault, JC Kufe, D TI Dendritic cell tumor fusions as a novel tumor vaccine: A phase I trial for patients with metastatic breast cancer. SO BLOOD LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 45 BP 14A EP 14A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100046 ER PT J AU Takemoto, CM Yoon, J Fisher, DE AF Takemoto, CM Yoon, J Fisher, DE TI Identification and characterization of a novel mast cell isoform of Mitf, a critical transcription factor for mast cell development. SO BLOOD LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 51 BP 15A EP 15A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100052 ER PT J AU Hsu, K Rhodes, J Liu, TX Kanki, JP Paw, B Zon, LI Look, AT AF Hsu, K Rhodes, J Liu, TX Kanki, JP Paw, B Zon, LI Look, AT TI Pu.1 is expressed by early granulocytic progenitors in the zebrafish. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 63 BP 18A EP 18A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100064 ER PT J AU Tzachanis, D van Puijenbroek, AAFL Berezovskaya, A Freeman, GJ Nadler, LM Boussiotis, VA AF Tzachanis, D van Puijenbroek, AAFL Berezovskaya, A Freeman, GJ Nadler, LM Boussiotis, VA TI Anergic T cells selectively express ARF6, a GTP-binding protein, which inhibits T cell activation by regulating actin-cytoskeleton remodeling. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 73 BP 20A EP 21A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134100074 ER PT J AU van Puijenbroek, AAFL Freeman, GJ Nadler, LM Boussiotis, VA AF van Puijenbroek, AAFL Freeman, GJ Nadler, LM Boussiotis, VA TI RIAM, a novel RAP1-interacting adaptor molecule with stuctural and functional features involved in cytoskeleton organization. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 79 BP 22A EP 22A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100080 ER PT J AU Feng, SJ Resendiz, JC Lu, X Ji, GL Kroll, MH AF Feng, SJ Resendiz, JC Lu, X Ji, GL Kroll, MH TI Pathological shear stress stimulates alpha IIb beta 3-dependent signaling. SO BLOOD LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 99 BP 26A EP 26A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100100 ER PT J AU Resendiz, JC Feng, SJ Ji, GL Lu, X Kroll, MH AF Resendiz, JC Feng, SJ Ji, GL Lu, X Kroll, MH TI Activation of SLP-76 by shear-induced von Willebrand factor binding to platelet alpha IIb beta 3. SO BLOOD LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 102 BP 27A EP 27A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100103 ER PT J AU Ding, KY Ni, HY Wu, JS Zhai, ZM Xu, XC Sun, ZM Wang, ML Wagner, DD AF Ding, KY Ni, HY Wu, JS Zhai, ZM Xu, XC Sun, ZM Wang, ML Wagner, DD TI Increased platelet fibronectin content in a family with hypofibrinogenemia. SO BLOOD LA English DT Meeting Abstract C1 Anhui Prov Hosp, Dept Hematol, Ctr Lab, Hefei, Peoples R China. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Anhui Med Univ, Hefei, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3806 BP 49B EP 49B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200219 ER PT J AU Shohet, JL Henn, TJ Gianchancani, Y Denes, F Gauget, JM von Andrian, U Shohet, SB AF Shohet, JL Henn, TJ Gianchancani, Y Denes, F Gauget, JM von Andrian, U Shohet, SB TI Plasma discharge in "artificial blood vessels". SO BLOOD LA English DT Meeting Abstract C1 Univ Wisconsin, Madison, WI USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3843 BP 57B EP 57B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200256 ER PT J AU Shohet, JL Denes, F Esnault, S Manolache, S Henn, TJ Gianchandani, Y von Andrian, U Shohet, SB AF Shohet, JL Denes, F Esnault, S Manolache, S Henn, TJ Gianchandani, Y von Andrian, U Shohet, SB TI Cell adhesion to plasma-treated surfaces. SO BLOOD LA English DT Meeting Abstract C1 Univ Wisconsin, Engn Res Ctr Plasma Aided Mfg, Madison, WI 53706 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3842 BP 57B EP 57B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200255 ER PT J AU Eckermann, JM Buhler, LH Zhu, A Cooper, DKC AF Eckermann, JM Buhler, LH Zhu, A Cooper, DKC TI An investigation of the potential of modified porcine erythrocytes for xenogeneic transfusion in primates. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 254 BP 63A EP 63A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100255 ER PT J AU Okuno, Y Iwasaki, H Huettner, CS Radomska, HS Akashi, K Tenen, DG AF Okuno, Y Iwasaki, H Huettner, CS Radomska, HS Akashi, K Tenen, DG TI A human CD34 genomic PAC clone targets hematopoietic stem cells in transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 258 BP 64A EP 64A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100259 ER PT J AU Stier, S Cheng, T Carlesso, N Scadden, DT AF Stier, S Cheng, T Carlesso, N Scadden, DT TI Notch1 activation enhances stem cell self renewal in vivo and promotes early lymphoid commitment. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr,AIDS Res Ctr, Boston, MA USA. Univ Bonn, Med Poliklin, D-5300 Bonn, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 264 BP 65A EP 65A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100265 ER PT J AU Adams, GB Olson, DP Szczepiorkowski, ZM Kos, C Pollack, MR Clingensmith, BL Brown, EM Scadden, DT AF Adams, GB Olson, DP Szczepiorkowski, ZM Kos, C Pollack, MR Clingensmith, BL Brown, EM Scadden, DT TI Bone mineral contributes to bone marrow hematopoiesis through the calcium sensing receptor. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Blood Transfus Serv, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrine Hypertens,Membrane Biol Program, Boston, MA USA. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 274 BP 67A EP 67A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100275 ER PT J AU Rhodes, J Kanki, JP Look, AT AF Rhodes, J Kanki, JP Look, AT TI The role of Pu.1 in zebrafish hematopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 276 BP 68A EP 68A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100277 ER PT J AU Wang, ZY Miura, N Bonelli, A Mole, P Carlesso, N Scadden, DT AF Wang, ZY Miura, N Bonelli, A Mole, P Carlesso, N Scadden, DT TI Receptor tyrosine kinase, EphB4 (HTK), accelerates differentiation of select human hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 279 BP 68A EP 68A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100280 ER PT J AU Manz, MG Miyamoto, T Akashi, K Weissman, IL AF Manz, MG Miyamoto, T Akashi, K Weissman, IL TI Myeloid committed early hematopoietic progenitors in adult human bone marrow. SO BLOOD LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 292 BP 71A EP 71A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100293 ER PT J AU Classon, M Scadden, DT Carlesso, N AF Classon, M Scadden, DT Carlesso, N TI Notch promotes cell cycle entry by decreasing the CDK inhibitors p21(cip1) and p27(kip1). SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Lisbon, Sch Med, Inst Histol & Embriol, CEBIP, P-1699 Lisbon, Portugal. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 334 BP 80A EP 81A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134100335 ER PT J AU Palomero, T Langenau, DM Kanki, JP Ferrando, AA Look, AT AF Palomero, T Langenau, DM Kanki, JP Ferrando, AA Look, AT TI Developmental regulation of Hox11 (Tlx-1) in organogenesis and acute leukemia. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 400 BP 96A EP 96A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100401 ER PT J AU Dzik, WH Grabowski, EF Feng, S Ko, D Cosimi, B Israel, EJ Vacanti, J AF Dzik, WH Grabowski, EF Feng, S Ko, D Cosimi, B Israel, EJ Vacanti, J TI Preliminary experience with rFVIIa in children undergoing orthotopic liver transplantation. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4056 BP 104B EP 104B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200469 ER PT J AU Song, HD Liu, TX Wu, XY Shun, XJ Zhang, QH Chen, SJ Zhou, Y Chen, Z Look, TA Zon, LI AF Song, HD Liu, TX Wu, XY Shun, XJ Zhang, QH Chen, SJ Zhou, Y Chen, Z Look, TA Zon, LI TI Gene expression profiling in kidney of zebrafish's hematopoietic tissue. SO BLOOD LA English DT Meeting Abstract C1 Rui Jin Hosp, Shanghai Inst Hematol, SSMU, Shanghai, Peoples R China. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4137 BP 121B EP 121B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200550 ER PT J AU Lu, J Pazin, M Ravid, K AF Lu, J Pazin, M Ravid, K TI Properties of Ets-1 binding to chromatin: Its role in megakaryocyte gene expression. SO BLOOD LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, CBRC, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4173 BP 128B EP 128B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200584 ER PT J AU Park, H Rouiffe, G Shelley, CS Olson, D Scadden, DT Arnaout, MA AF Park, H Rouiffe, G Shelley, CS Olson, D Scadden, DT Arnaout, MA TI ZBP-89 represses CD11b gene expression during the differentiation of monocytes into macrophages. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Leukocyte Biol & Inflammat Program, Charlestown, MA USA. Massachusetts Gen Hosp, Expt Hematol & AIDS Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4178 BP 129B EP 129B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200589 ER PT J AU Shelley, CS Da Silva, N Teodoridis, JM AF Shelley, CS Da Silva, N Teodoridis, JM TI During U937 monocytic differentiation repression of the CD43 gene promoter is mediated by the single-stranded DNA binding protein Pur alpha. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4183 BP 130B EP 130B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200594 ER PT J AU Stone, R Galinsky, I Haynes, H Soiffer, R Alyea, E Neuberg, D Tawa, M Antin, J Resta, D Granter, S DeAngelo, D AF Stone, R Galinsky, I Haynes, H Soiffer, R Alyea, E Neuberg, D Tawa, M Antin, J Resta, D Granter, S DeAngelo, D TI Skin reactions to imatinib mesylate (STI-571) in patients with chronic myeloid leukemia (CML): Clinical features and histopathology. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 592 BP 141A EP 141A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100593 ER PT J AU Scheijen, B Gesbert, F Griffin, JD AF Scheijen, B Gesbert, F Griffin, JD TI Regulation of Forkhead transcription factors by Bcr/Abl signaling. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. RI Scheijen, Blanca/E-3523-2016 OI Scheijen, Blanca/0000-0001-8029-9230 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 607 BP 144A EP 144A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100608 ER PT J AU Tse, WT Egalka, MC Pendleton, JD Guinan, EC AF Tse, WT Egalka, MC Pendleton, JD Guinan, EC TI Human marrow stromal cells suppress growth factor-dependent proliferation of TF-1 erythroleukemic cells by a TGF-independent mechanism. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4259 BP 147B EP 147B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200670 ER PT J AU Anderson, KS von Bergwelt-Baildon, MS Vonderheide, RH Richardson, PG Schlossman, RL Anderson, KC Nadler, LM Schultze, JL AF Anderson, KS von Bergwelt-Baildon, MS Vonderheide, RH Richardson, PG Schlossman, RL Anderson, KC Nadler, LM Schultze, JL TI Functional deficits of virus specific cytoxic T cells in patients with multiple myeloma: Impact on cancer vaccine development. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 654 BP 155A EP 155A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100655 ER PT J AU Tai, YT Podar, K Wang, FF Lin, B Gupta, D Faith, D Koike, M Anderson, KC AF Tai, YT Podar, K Wang, FF Lin, B Gupta, D Faith, D Koike, M Anderson, KC TI Translocation of Ku86/Ku70 to the multiple myeloma cell membrane: Functional implication. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Inst Radiol Serv, Genome Res Grp, Anagawa, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 678 BP 161A EP 161A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100679 ER PT J AU Lin, BK Podar, K Gupta, D Tai, YT Hideshima, T Lentzsch, S Davies, FE Griffin, JD Weissberg, E Schlossman, RL Richardson, PG Wood, J Anderson, KC AF Lin, BK Podar, K Gupta, D Tai, YT Hideshima, T Lentzsch, S Davies, FE Griffin, JD Weissberg, E Schlossman, RL Richardson, PG Wood, J Anderson, KC TI The VEGF receptor tyrosine kinase inhibitor PTK787 inhibits proliferation and migration of multiple myeloma cells, and reduces paracrine-mediated responses to the bone marrow microenvironment. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Novartis Pharmaceut, Basel, Switzerland. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 699 BP 166A EP 166A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100700 ER PT J AU Alyea, EP Neuberg, D Canning, C Hochberg, E Parikh, B Webb, IJ Fisher, DC Saidman, S Antin, J Soiffer, RJ Ritz, J AF Alyea, EP Neuberg, D Canning, C Hochberg, E Parikh, B Webb, IJ Fisher, DC Saidman, S Antin, J Soiffer, RJ Ritz, J TI Nonmyeloablative conditioning with low dose intravenous busulfan and fludarabine is safe and sufficient to obtain allogeneic stem cell engraftment in patients with hematologic malignancies. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 778 BP 185A EP 185A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100779 ER PT J AU DeAngelo, D Russo, D Castaigne, S Esteve, J Burnett, A Goldstone, A Tallman, M Bradstock, K Lowenberg, B Leopold, L Munteanu, M Eten, C Berger, M AF DeAngelo, D Russo, D Castaigne, S Esteve, J Burnett, A Goldstone, A Tallman, M Bradstock, K Lowenberg, B Leopold, L Munteanu, M Eten, C Berger, M TI Preliminary report of the safety and efficacy of gemtuzumab ozogamicin (Mylotarg (R)) given in combination with cytarabine and daunorubicin in patients with acute myeloid leukemia. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Udine Univ Hosp, Udine, Italy. Hosp A Mignot, Le Chesnay, France. Hosp Clin Barcelona, Barcelona, Spain. Cardiff Univ, Cardiff CF1 3NS, S Glam, Wales. UCL Hosp, London, England. Northwestern Univ, Sch Med, Chicago, IL USA. Westmead Hosp, Westmead, NSW 2145, Australia. Univ Rotterdam Hosp, Rotterdam, Netherlands. Wyeth Ayerst Res, Collegeville, PA USA. RI Russo, Domenico/C-3947-2011 NR 0 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4500 BP 199B EP 199B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200911 ER PT J AU Massarweh, S Varadhachary, G Ho, VT Bharwani, L AF Massarweh, S Varadhachary, G Ho, VT Bharwani, L TI Natural killer acute lymphoblastic leukemia; Case description and potential role for maintenance chemotherapy. SO BLOOD LA English DT Meeting Abstract C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. RI Massarweh, Suleiman/O-1332-2013 NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4516 BP 203B EP 203B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134200927 ER PT J AU Devereux, S Walker, SJ Pizzato, M Takeuchi, Y AF Devereux, S Walker, SJ Pizzato, M Takeuchi, Y TI Heparin binds to murine leukaemia virus and inhibits both envelope independent attachment and infection. SO BLOOD LA English DT Meeting Abstract C1 GKT Sch Med, London, England. UCL, London, England. Dana Farber Canc Inst, Boston, MA 02115 USA. UCL, Wohl Vir Ctr, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 872 BP 209A EP 210A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134100876 ER PT J AU Adachi, D Oda, T Yagasaki, H Nakasato, K Taniguchi, T D'Andrea, AD Asano, S Yamashita, T AF Adachi, D Oda, T Yagasaki, H Nakasato, K Taniguchi, T D'Andrea, AD Asano, S Yamashita, T TI Different activation of the Fanconi anemia (FA) pathway by patient-derived FANCA mutants. SO BLOOD LA English DT Meeting Abstract C1 Univ Tokyo, Inst Med Sci, Div Genet Diagnosis, Tokyo, Japan. Univ Tokyo, Inst Med Sci, Dept Mol Therapy, Adv Clin Res Ctr, Tokyo, Japan. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 896 BP 215A EP 215A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100900 ER PT J AU Gazda, H Zhong, R Sieff, CA AF Gazda, H Zhong, R Sieff, CA TI Identification of ribosomal protein and other candidate genes in Diamond-Blackfan Anemia on chromosome 8p and analysis of their expression. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 908 BP 218A EP 218A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100912 ER PT J AU Alazraki, NP Leigh, BR Carter, WL Fischman, AJ Janicek, MJ Thrall, JH Sandler, MP Waxman, A Landin, R White, CA AF Alazraki, NP Leigh, BR Carter, WL Fischman, AJ Janicek, MJ Thrall, JH Sandler, MP Waxman, A Landin, R White, CA TI Gastrointestinal adverse events associated with Zevalin (TM) radioimmunotherapy do not correlate with nuclear medicine imaging findings. SO BLOOD LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Med Ctr, Atlanta, GA USA. Sharp Mem Hosp & Rehabil Ctr, SD Diagnost Radiol Med Grp, San Diego, CA 90034 USA. Idec Pharmaceut Corp, San Diego, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4621 BP 226B EP 226B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201032 ER PT J AU Appleman, LJ van Puijenbroek, AAFL Nadler, LM Boussiotis, VA AF Appleman, LJ van Puijenbroek, AAFL Nadler, LM Boussiotis, VA TI Lithium chloride substitutes for CD28 but not for T cell receptor (TCR) mediated signals in primary human T lymphocytes. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 972 BP 232A EP 232A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100976 ER PT J AU Kim, YS Baek, KH Jung, SK Chung, HM Ko, JJ Andrea, AD AF Kim, YS Baek, KH Jung, SK Chung, HM Ko, JJ Andrea, AD TI DUB-1A, a novel deubiqutinating enzyme in B-lymphocytes SO BLOOD LA English DT Meeting Abstract C1 Pochon CHA Univ, CHA Gen Hosp, Seoul, South Korea. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 992 BP 237A EP 237A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134100996 ER PT J AU Feng, SJ Resendiz, JC Lu, X Ji, GL Berndt, MC Kroll, MH AF Feng, SJ Resendiz, JC Lu, X Ji, GL Berndt, MC Kroll, MH TI Cytoplasmic domains of platelet glycoprotein Ib alpha regulate filamin 1a binding. SO BLOOD LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. Baker Med Res Inst, Prahran, Vic 3181, Australia. RI Berndt, Michael/D-5580-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1007 BP 240A EP 240A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101011 ER PT J AU Turner, RB Liu, L Sazonova, IY Reed, GL AF Turner, RB Liu, L Sazonova, IY Reed, GL TI Structural elements that govern the substrate specificity of the clot dissolving enzyme plasmin. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1069 BP 255A EP 255A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101073 ER PT J AU Robinson, BR Sazonova, IY Houng, ALK Reed, GL AF Robinson, BR Sazonova, IY Houng, ALK Reed, GL TI Kringle domains play a critical role in indirect plasminogen activation. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1074 BP 256A EP 256A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101078 ER PT J AU Mayerhofer, M Valent, P Griffin, JD Sillaber, C AF Mayerhofer, M Valent, P Griffin, JD Sillaber, C TI The BCR/ABL onocogene induces VEGF gene expression in BA/F3 cells through activation of phosphoinositol-3 kinase. SO BLOOD LA English DT Meeting Abstract C1 Univ Vienna, Dept Internal Med 1, Div Hematol & Hemstaseol, Vienna, Austria. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4782 BP 262B EP 263B PN 2 PG 2 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201193 ER PT J AU Iwasaki, H Akashi, K AF Iwasaki, H Akashi, K TI Mast cells originate from granulocyte/macrophage-committed progenitors. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1156 BP 275A EP 275A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101160 ER PT J AU Kojika, S Wu, L Griffin, JD AF Kojika, S Wu, L Griffin, JD TI Differential regulation of Id genes by intracellular, Notch1 in hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1184 BP 281A EP 281A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101188 ER PT J AU Xu, YF Kennedy, B Harlow, E Orkin, SH Crispino, JD AF Xu, YF Kennedy, B Harlow, E Orkin, SH Crispino, JD TI EPS, a novel repressor of SCL/tal-1 and E12 bHLH proteins in hematopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Univ Chicago, Ben May Inst, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Childrens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1189 BP 282A EP 282A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101193 ER PT J AU Iwasaki-Arai, J Iwasaki, H Akashi, K AF Iwasaki-Arai, J Iwasaki, H Akashi, K TI GM-CSF signals can play both permissive and instructive roles in hematopoietic lineage determination. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Cancer Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1215 BP 288A EP 288A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101219 ER PT J AU Makower, D Lee, S Wiernik, PH Paietta, E Bennett, JM Wade, J Ghosh, C Kaminer, L Tallman, MS AF Makower, D Lee, S Wiernik, PH Paietta, E Bennett, JM Wade, J Ghosh, C Kaminer, L Tallman, MS TI Phase II trial of theophylline for early stage chronic lymphocytic leukemia (CLL). SO BLOOD LA English DT Meeting Abstract C1 Montefiore Med Ctr, Bronx, NY 10467 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Our Lady Mercy Med Ctr, Bronx, NY USA. Univ Rochester, Ctr Canc, Rochester, NY USA. Decatur Mem Hosp, Decatur, IL USA. Cedar Rapids Oncol Associates, Cedar Rapids, IA USA. Northwestern Univ, Evanston Hosp, Evanston, IL 60201 USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4905 BP 290B EP 290B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201316 ER PT J AU Carlesso, N Chora, A Cruz, E Sarmento, L Jon, A Cardoso, AA Scadden, DT AF Carlesso, N Chora, A Cruz, E Sarmento, L Jon, A Cardoso, AA Scadden, DT TI Modulation of Notch and Jagged2 in the bone marrow microenvironment with TNF alpha stimulation. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1244 BP 295A EP 295A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101248 ER PT J AU Ladetto, M Omede, P Sametti, S Donovan, JW Drandi, D Giaccone, L Volpato, F Astolfi, M Giaretta, F Palumbo, A Bruno, B Pileri, A Gribben, JG Boccadoro, M AF Ladetto, M Omede, P Sametti, S Donovan, JW Drandi, D Giaccone, L Volpato, F Astolfi, M Giaretta, F Palumbo, A Bruno, B Pileri, A Gribben, JG Boccadoro, M TI Real time PCR in multiple myeloma: Quantitative analysis of tumor contamination of stem cell harvests. SO BLOOD LA English DT Meeting Abstract C1 Univ Turin, Cattedra Ematol, Turin, Italy. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI drandi, daniela/Q-6504-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4948 BP 300B EP 300B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201359 ER PT J AU Matsunaga, T Kurosawa, H Inaba, T Matsui, H Okuya, M Inukai, T Funabiki, T Look, AT Eguchi, M AF Matsunaga, T Kurosawa, H Inaba, T Matsui, H Okuya, M Inukai, T Funabiki, T Look, AT Eguchi, M TI ANNEXIN II, a proposed cause of coagulopathy with APL, is the downstream target of the E2A-HLF oncoprotein and is regulated by cytokine-initiated signaling pathways. SO BLOOD LA English DT Meeting Abstract C1 Dokkyo Univ, Sch Med, Mibu, Tochigi 32102, Japan. Hiroshima Univ, Res Inst Radiat Biol & Med, Hiroshima, Japan. Yamanashi Med Univ, Yamanashi, Japan. Yokohama City Univ, Sch Med, Yokohama, Kanagawa 232, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1279 BP 303A EP 303A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101283 ER PT J AU Chiaretti, S Gentleman, R Wang, K Vitale, A Ritz, J Foa, R AF Chiaretti, S Gentleman, R Wang, K Vitale, A Ritz, J Foa, R TI Gene expression profiles of adult acute lymphocytic leukemia (ALL) reveal distinct genetic patterns that correlate with cell surface phenotype, chromosomal abnormalities and clinical oucome. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, Rome, Italy. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1282 BP 304A EP 304A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101286 ER PT J AU Van Ness, B Griffin, S Zhao, F Oken, M Rue, M AF Van Ness, B Griffin, S Zhao, F Oken, M Rue, M TI Genetic Polymorphisms in multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 Univ Minnesota, Ctr Canc, Minneapolis, MN USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 4974 BP 305B EP 305B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201385 ER PT J AU Sawafuji, K Miyakawa, Y Weisberg, E Griffin, JD Ikeda, Y Kizaki, M AF Sawafuji, K Miyakawa, Y Weisberg, E Griffin, JD Ikeda, Y Kizaki, M TI Effects of aminopeptidase inhibitors on STI571 resistant CML cell lines. SO BLOOD LA English DT Meeting Abstract C1 Keio Univ, Sch Med, Tokyo, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1306 BP 309A EP 309A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101310 ER PT J AU Buhler, L Kurilla-Mahon, B Abraham, S Alwayn, I Appel, J Newman, D Awwad, M White-Scharf, ME Sachs, DH Sackstein, R Cooper, DKC Down, JD AF Buhler, L Kurilla-Mahon, B Abraham, S Alwayn, I Appel, J Newman, D Awwad, M White-Scharf, ME Sachs, DH Sackstein, R Cooper, DKC Down, JD TI Effects of mycophenolate mofetil on hematopoietic progenitor cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. BioTransplant Inc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 5010 BP 313B EP 313B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201421 ER PT J AU McDermott, DF Vasir, D Joyce, R Levine, J Uhl, L Fardy, L Giallombardo, N Hurley, D Tetreault, JC Kufe, D Avigan, D AF McDermott, DF Vasir, D Joyce, R Levine, J Uhl, L Fardy, L Giallombardo, N Hurley, D Tetreault, JC Kufe, D Avigan, D TI Dendritic cell chimerism and immune reconstitution following non-myeloablative transplantation. SO BLOOD LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 5033 BP 319B EP 319B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201444 ER PT J AU Ruffner, KL Radich, JP Bryant, E Maziarz, RT Rosamilia, M Druker, BJ Chauncey, TR AF Ruffner, KL Radich, JP Bryant, E Maziarz, RT Rosamilia, M Druker, BJ Chauncey, TR TI Serial cytogenetic and quantitative molecular monitoring of disease burden in a patient on imatinib (STI-571) for CML-AP undergoing G-CSF mobilization of peripheral blood stem cells (PBSC). SO BLOOD LA English DT Meeting Abstract C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Novartis Pharmaceut, E Hanover, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1356 BP 321A EP 321A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101360 ER PT J AU Zubair, AC Freedman, AS Gribben, JG Friedberg, J Ritz, J Webb, IJ AF Zubair, AC Freedman, AS Gribben, JG Friedberg, J Ritz, J Webb, IJ TI Neutrophil engraftment is a better predictor of long-term hematopoietic function than number of CD34 positive cells infused. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Canc Inst, TCH, Joint Program Transfus Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 5053 BP 323B EP 323B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201464 ER PT J AU Ghia, P Husson, H Cardoso, AA Schultze, J Munoz, O Strola, G Carideo, EG Caligaris-Cappio, F Freedman, AS AF Ghia, P Husson, H Cardoso, AA Schultze, J Munoz, O Strola, G Carideo, EG Caligaris-Cappio, F Freedman, AS TI CXCL13/BCA-1 is produced by follicular lymphoma cells: Role in the accumulation and architectural organization of malignant B cells. SO BLOOD LA English DT Meeting Abstract C1 Inst Canc Res & Treatment, Lab Canc Immunol, Candiolo, TO, Italy. Univ Turin, Dept Biomed Sci & Human Oncol, I-10124 Turin, Italy. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1395 BP 330A EP 331A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101399 ER PT J AU Wilson, WH Pittaluga, S O'Connor, P Hegde, U Drbohlav, N Janik, J Little, R Steinberg, S Cheson, B Staudt, L Raffeld, M Chabner, B Jaffe, ES AF Wilson, WH Pittaluga, S O'Connor, P Hegde, U Drbohlav, N Janik, J Little, R Steinberg, S Cheson, B Staudt, L Raffeld, M Chabner, B Jaffe, ES TI Rituximab may overcome bcl-2-associated chemotherapy resistance in untreated diffuse large B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 Natl Canc Inst, Ctr Canc Res, Bethesda, MD USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1447 BP 343A EP 343A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101451 ER PT J AU Laver, JH Weinstein, HJ Hutchison, RE Kepner, J Schwenn, M Tarbell, N Desai, S Murphy, SB AF Laver, JH Weinstein, HJ Hutchison, RE Kepner, J Schwenn, M Tarbell, N Desai, S Murphy, SB TI Lineage-specific differences in outcome for advanced stage large cell lymphoma in children and adolescents: Results of a randomized phase III Pediatric Oncology Group trial. SO BLOOD LA English DT Meeting Abstract C1 Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Syracuse, Syracuse, NY USA. Univ Florida, Gainesville, FL 32611 USA. Univ Massachusetts, Worcester, MA 01605 USA. Cross Canc Ctr, Edmonton, AB, Canada. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1455 BP 345A EP 345A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101459 ER PT J AU Restrepo, A Restrepo, ML Devore, PE Callander, NS Schneider, DL Litofsky, ID Walsh, T Gokmen, E Ochoa, L Ehsan, A Patterson, JE Freytes, CO AF Restrepo, A Restrepo, ML Devore, PE Callander, NS Schneider, DL Litofsky, ID Walsh, T Gokmen, E Ochoa, L Ehsan, A Patterson, JE Freytes, CO TI Infectious during the early post-transplant period in patients undergoing autologous peripheral blood stem cell transplantation (APBSCT) for multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 5219 BP 361B EP 362B PN 2 PG 2 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201630 ER PT J AU Rai, KR Coutre, S Rizzieri, D Gribben, JG Flinn, I Rabinowe, S Keating, MJ AF Rai, KR Coutre, S Rizzieri, D Gribben, JG Flinn, I Rabinowe, S Keating, MJ CA Campath Study Grp TI Efficacy and safety of alemtuzumab (Campath-1H) in refractory B-CLL patients treated on a compassionate basis. SO BLOOD LA English DT Meeting Abstract C1 Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Duke Univ, Durham, NC 27706 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. St Francis Reg Canc Ctr, Hartford, CT USA. Mt Sinai Reg Canc Ctr, Hartford, CT USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 16 Z9 17 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1538 BP 365A EP 365A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101542 ER PT J AU Coutre, S Rai, KR Keating, MJ Gribben, JG Flinn, I Rabinowe, S Rizzieri, D AF Coutre, S Rai, KR Keating, MJ Gribben, JG Flinn, I Rabinowe, S Rizzieri, D CA Campath Study Grp TI Efficacy and safety of alemtuzumab (Campath-1H) used on a compassionate basis in refractory T-PLL. SO BLOOD LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. St Francis Reg Canc Ctr, Hartford, CT USA. Mt Sinai Reg Canc Ctr, Hartford, CT USA. Duke Univ, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1542 BP 366A EP 366A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101546 ER PT J AU Chauhan, D Auclair, D Li, GL Hideshima, T Podar, K Richardson, P Schlossman, RL Munshi, N Anderson, KC AF Chauhan, D Auclair, D Li, GL Hideshima, T Podar, K Richardson, P Schlossman, RL Munshi, N Anderson, KC TI Identification of genes regulated by 2-methoxyestradiol (2ME2) in multiple myeloma (MM) cells using oligonucleotide arrays. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1555 BP 369A EP 369A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101559 ER PT J AU Hayashi, T Hideshima, T Akiyama, M Richardson, P Schlossman, RL Chauhan, D Waxman, S Anderson, KC AF Hayashi, T Hideshima, T Akiyama, M Richardson, P Schlossman, RL Chauhan, D Waxman, S Anderson, KC TI Arsenic trioxide inhibits growth of human multiple myeloma cells in the bone marrow microenvironment. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mt Sinai Canc Ctr, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1578 BP 375A EP 375A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101582 ER PT J AU Hideshima, T Chauhan, D Castro, A Hayashi, T Mitsiades, C Mitsiades, N Akiyama, M Richardson, PG Schlossman, RL Adams, J Anderson, KC AF Hideshima, T Chauhan, D Castro, A Hayashi, T Mitsiades, C Mitsiades, N Akiyama, M Richardson, PG Schlossman, RL Adams, J Anderson, KC TI NF-kappa B as a therapeutic target in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1581 BP 375A EP 375A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101585 ER PT J AU Gupta, D Tai, YT Podar, K Lin, BK Akiyama, M LeBlanc, R Catley, LP Mitsiades, C Chauhan, D Mitsiades, N Hideshima, T Schlossman, RL Richardson, PG Anderson, KC AF Gupta, D Tai, YT Podar, K Lin, BK Akiyama, M LeBlanc, R Catley, LP Mitsiades, C Chauhan, D Mitsiades, N Hideshima, T Schlossman, RL Richardson, PG Anderson, KC TI beta-lapachone, a novel topoisomerase I inhibitor, has significant cytotoxicity against multiple myeloma (MM) cell lines and patient cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1583 BP 376A EP 376A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101587 ER PT J AU Mitsiades, CS Mitsiades, N Poulaki, V Treon, SP Anderson, KC AF Mitsiades, CS Mitsiades, N Poulaki, V Treon, SP Anderson, KC TI Thiazolidinediones: A novel class of agents with anti-myeloma activity. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1582 BP 376A EP 376A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101586 ER PT J AU Mitsiades, N Mitsiades, CS Poulaki, V Anderson, KC Treon, SP AF Mitsiades, N Mitsiades, CS Poulaki, V Anderson, KC Treon, SP TI The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) induces growth arrest and apoptosis in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) cell lines and patient tumor cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1584 BP 376A EP 376A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101588 ER PT J AU Mitsiades, N Mitsiades, CS Poulaki, V Anderson, KC Treon, SP AF Mitsiades, N Mitsiades, CS Poulaki, V Anderson, KC Treon, SP TI Intracellular regulation of tumor necrosis factor (TNF)-Related Apoptosis Inducing Ligand (TRAIL/Apo2L)-induced apoptosis in human multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1585 BP 376A EP 376A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101589 ER PT J AU Mitsiades, N Mitsiades, CS Poulaki, V Chauhan, D Hideshima, T Treon, SP Anderson, KC AF Mitsiades, N Mitsiades, CS Poulaki, V Chauhan, D Hideshima, T Treon, SP Anderson, KC TI NF-kappa B and p38 kinase as novel therapeutic targets for human multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1586 BP 376A EP 377A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101590 ER PT J AU Mitsiades, CS Mitsiades, N Poulaki, V Akiyama, M Treon, SP Anderson, KC AF Mitsiades, CS Mitsiades, N Poulaki, V Akiyama, M Treon, SP Anderson, KC TI The HSP90 molecular chaperone as a novel therapeutic target in hematologic malignancies. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 3 Z9 4 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1587 BP 377A EP 377A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101591 ER PT J AU Mapara, MY Kim, YM Sykes, M AF Mapara, MY Kim, YM Sykes, M TI Fate of alloreactive, antigen-specific CD8(+) T cells within donor lymphocyte infusions (DLI) administered to mixed hematopoietic chimeras. SO BLOOD LA English DT Meeting Abstract C1 Humboldt Univ, Charite, Med Ctr, Dept Hematol & Oncol, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RI mapara, markus/A-2134-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1601 BP 380A EP 380A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101605 ER PT J AU Kim, YM Mapara, MY Sykes, M AF Kim, YM Mapara, MY Sykes, M TI Predominant role of CD8(+) T cells in the lymphohematopoietic graft-versus-host reaction mediated by donor lymphocyte infusion (DLI) in murine mixed chimeras. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RI mapara, markus/A-2134-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1603 BP 381A EP 381A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101607 ER PT J AU Craiu, A Saito, Y Eppich, H Olson, D Cohen, K Freshman, J Dombkowski, D Richardson, PG Schlossman, RL Rich, R Mangano, J Anderson, KC Scadden, DT AF Craiu, A Saito, Y Eppich, H Olson, D Cohen, K Freshman, J Dombkowski, D Richardson, PG Schlossman, RL Rich, R Mangano, J Anderson, KC Scadden, DT TI Rapid and efficient purging of myeloma cells and preservation of CD34+progenitor cells using a novel flowing pulsed electric field (PEF) apparatus. SO BLOOD LA English DT Meeting Abstract C1 Sci Res Lab Inc, Somerville, MA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1643 BP 390A EP 390A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101647 ER PT J AU Gaudet, G Friedberg, J Kutok, J Neuberg, D Nadler, LM Freedman, AS AF Gaudet, G Friedberg, J Kutok, J Neuberg, D Nadler, LM Freedman, AS TI Autologous bone marrow transplantation (ABMT) for marginal zone B-cell non-Hodgkin's lymphomas (NHL). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 5351 BP 392B EP 392B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201762 ER PT J AU McCoy, AMG Smith, EP Atkinson, ME Baranski, B Kahl, BS Juckett, MB Mitchell, TL Gangnon, R Longo, WL AF McCoy, AMG Smith, EP Atkinson, ME Baranski, B Kahl, BS Juckett, MB Mitchell, TL Gangnon, R Longo, WL TI High dose thiotepa and etoposide: Long term experience with a novel conditioning regimen for autologous BM/PBPC transplant in 65 NHL patients. SO BLOOD LA English DT Meeting Abstract C1 Univ Wisconsin, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 5350 BP 392B EP 392B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201761 ER PT J AU Soiffer, RJ Galinsky, I DeAngelo, D Alyea, EP Antin, JH Restas, D Stone, RM AF Soiffer, RJ Galinsky, I DeAngelo, D Alyea, EP Antin, JH Restas, D Stone, RM TI Imatinib mesylate (Gleevec) for disease relapse following allogeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1682 BP 400A EP 400A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101686 ER PT J AU Bellucci, R Wu, CJ Munshi, NC Alyea, ER Anderson, KC Ritz, J AF Bellucci, R Wu, CJ Munshi, NC Alyea, ER Anderson, KC Ritz, J TI Identification of target antigens associated with graft-vs-myeloma response after allogeneic bone marrow transplantation and donor lymphocyte infusion. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1702 BP 405A EP 405A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101706 ER PT J AU Shimamura, A de Oca, RM Svenson, J Moreau, L Garcia-Higuera, I Taniguchi, T Wagner, JE Grompe, M Nathan, DG Sieff, C d'Andrea, AD AF Shimamura, A de Oca, RM Svenson, J Moreau, L Garcia-Higuera, I Taniguchi, T Wagner, JE Grompe, M Nathan, DG Sieff, C d'Andrea, AD TI Correction of the Fanconi anemia (FA) pathway by retroviral transduction: Implications for FA diagnosis, subtyping, and gene therapy. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 5434 BP 411B EP 411B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201845 ER PT J AU Spitzer, TR Delmonico, F Tolkoff-Rubin, N Kraus, A McAfee, S Sackstein, R Dey, BR Colby, C Saidman, S Sachs, DH Sykes, M Cosimi, AB AF Spitzer, TR Delmonico, F Tolkoff-Rubin, N Kraus, A McAfee, S Sackstein, R Dey, BR Colby, C Saidman, S Sachs, DH Sykes, M Cosimi, AB TI The induction of sustained allograft tolerance and anti-tumor responses following combined HLA-matched donor bone marrow and renal transplantation for multiple myeloma with end-stage renal disase. SO BLOOD 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 AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1729 BP 412A EP 412A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101733 ER PT J AU Shklovskiy-Kordi, N Zingerman, B Rivkind, N Goldberg, S Krol, M Davis, S Freireich, E Varticovski, L Vorobiev, A AF Shklovskiy-Kordi, N Zingerman, B Rivkind, N Goldberg, S Krol, M Davis, S Freireich, E Varticovski, L Vorobiev, A TI Use of computerized, time-sensitive multimedia case presentation for clinical outcome analysis. SO BLOOD LA English DT Meeting Abstract C1 Natl Ctr Hematol, Moscow, Russia. Diagnost Ctr NI, Bryansk, Russia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Hosp, New York, NY 10029 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 5450 BP 415B EP 415B PN 2 PG 1 WC Hematology SC Hematology GA 491WZ UT WOS:000172134201861 ER PT J AU Dey, BR McAfee, SL Colby, C Sackstein, R Saidman, S Power, K Sachs, DH Sykes, M Spitzer, TR AF Dey, BR McAfee, SL Colby, C Sackstein, R Saidman, S Power, K Sachs, DH Sykes, M Spitzer, TR TI Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-vs-host disease (GvHD) and anti-tumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic stem cell transplantation (SCT). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1749 BP 417A EP 417A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101753 ER PT J AU Dey, BR McAfee, SL Sackstein, R Colby, C Sahai, S Saidman, S Power, K Kraus, A Sachs, DH Sykes, M Spitzer, TR AF Dey, BR McAfee, SL Sackstein, R Colby, C Sahai, S Saidman, S Power, K Kraus, A Sachs, DH Sykes, M Spitzer, TR TI Achievement of sustained remissions despite loss of donor chimerism (DC) in patients with chemotherapy-refractory non-Hodgkin's lymphoma (NHL) treated with nonmyeloablative conditioning and allogeneic stem cell transplantation (SCT). SO BLOOD 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 AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1753 BP 418A EP 418A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101757 ER PT J AU Mueller, L Saeki, Y Heister, T Heid, I Ackermann, M Dilloo, D Fraefel, C AF Mueller, L Saeki, Y Heister, T Heid, I Ackermann, M Dilloo, D Fraefel, C TI Helper virus-free HSV-1 amplicon-vectors for liver and muscle directed gene transfer of the secreted alkaline phosphatase (SEAP): Extended gene-expression by HSV-1/AAV and HSV-1/EBV hybrid vectors. SO BLOOD LA English DT Meeting Abstract C1 Univ Zurich, Inst Virol, Zurich, Switzerland. Massachusetts Gen Hosp, Charlestoen, MA USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1780 BP 424A EP 424A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101784 ER PT J AU Han, AP Yu, CN Lu, LR Fujiwara, Y Browne, C Chin, G Fleming, M Leboulch, P Orkin, SH Chen, JJ AF Han, AP Yu, CN Lu, LR Fujiwara, Y Browne, C Chin, G Fleming, M Leboulch, P Orkin, SH Chen, JJ TI HRI is necessary for regulation of globin translation and survival of erythroid precursors in iron-deficiency. SO BLOOD LA English DT Meeting Abstract C1 MIT, Harvard MIT Div Hth Sci & Technol, Cambridge, MA 02139 USA. Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1821 BP 434A EP 434A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101825 ER PT J AU Hrachovinova, I Andre, P Kazazian, HH Wagner, DD AF Hrachovinova, I Andre, P Kazazian, HH Wagner, DD TI Soluble P-selectin shortens bleeding time by inducing tissue factor bearing microparticles in hemophilia A mice. SO BLOOD 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. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1869 BP 446A EP 446A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101873 ER PT J AU Hoffmeister, KM Felbinger, TW Falet, H Denis, CV Wagner, DD von Andrian, UH Stossel, TP Hartwig, JH AF Hoffmeister, KM Felbinger, TW Falet, H Denis, CV Wagner, DD von Andrian, UH Stossel, TP Hartwig, JH TI Mechanism for rapid clearance of transfused chilled platelets. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1887 BP 450A EP 451A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101891 ER PT J AU Saleque, S Cameron, S Orkin, SH AF Saleque, S Cameron, S Orkin, SH TI The protooncogene Gfi-1b is essential for development of both erythroid and megakaryocytic lineages in vivo. SO BLOOD LA English DT Meeting Abstract C1 Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1889 BP 451A EP 451A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101893 ER PT J AU Sasaki, K Burel, S Zhang, DE Golub, TR AF Sasaki, K Burel, S Zhang, DE Golub, TR TI AML1/ETO impairs the interferon gamma transcriptional response. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Scripps Res Inst, La Jolla, CA USA. MIT, Ctr Genome Res, Cambridge, MA USA. Whitehead Inst, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1908 BP 456A EP 456A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101912 ER PT J AU Becton, D Ravindranath, Y Dahl, GV Berkow, RL Chang, M Stine, K Behm, FG Raimondi, SC Massey, G Weinstein, HJ AF Becton, D Ravindranath, Y Dahl, GV Berkow, RL Chang, M Stine, K Behm, FG Raimondi, SC Massey, G Weinstein, HJ TI A phase III study of intensive cytarabine (ara-C) induction followed by cyclosporine (CSA) modulation of drug resistance in de novo pediatric AML; POG 9421. SO BLOOD LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Childrens Oncol Grp, Arcadia, CA USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Michigan, Detroit, MI USA. Stanford Univ, Palo Alto, CA 94304 USA. St Jude Childrens Res Hosp, Memphis, TN USA. Univ Virginia, Coll Med, Charlottesville, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1929 BP 461A EP 461A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101933 ER PT J AU DeAngelo, DJ Dranoff, G Galinsky, I Hardy, S Mihm, M Webb, IJ Kojika, S Griffin, JD Stone, RM AF DeAngelo, DJ Dranoff, G Galinsky, I Hardy, S Mihm, M Webb, IJ Kojika, S Griffin, JD Stone, RM TI A phase I study of vaccination with lethally irradiated, autologous myeloblasts engineered by adenoviral mediated gene transfer to secrete human granulocyte-macrophase colony stimulating factor. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. CellGenesys, Foster City, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1935 BP 463A EP 463A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101939 ER PT J AU Van Etten, RA Aster, J Gilliland, DG Million, RP AF Van Etten, RA Aster, J Gilliland, DG Million, RP TI The Tel/Abl (ETV6/Abl) tyrosine kinase induces distinct myeloproliferative disease in mice that requires the Tel oligomerization domain and a direct binding site for Grb2. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1955 BP 468A EP 468A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101959 ER PT J AU Sattler, M Pride, YB Quinnan, LR Malouf, NA Salgia, R Gesbert, F Griffin, JD AF Sattler, M Pride, YB Quinnan, LR Malouf, NA Salgia, R Gesbert, F Griffin, JD TI Signaling defects associated with mutation of tyrosine-177 of BCR/ABL. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1959 BP 469A EP 469A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101963 ER PT J AU Battle, T Frank, D AF Battle, T Frank, D TI Activation of the STAT signaling pathway is required for CLL differentiation in response to bryostatin 1. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1973 BP 472A EP 472A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101977 ER PT J AU Chauhan, D Sattler, M Li, GL Hideshima, T LeBlanc, R Catley, L Gupta, D Richardson, P Schlossman, RL Munshi, N Anderson, KC AF Chauhan, D Sattler, M Li, GL Hideshima, T LeBlanc, R Catley, L Gupta, D Richardson, P Schlossman, RL Munshi, N Anderson, KC TI 2-methoxyestradiol (2ME2) acts directly on tumor cells and in the bone marrow microenvironment to overcome drug resistance in multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1977 BP 473A EP 473A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101981 ER PT J AU Lentzsch, S Rogers, M LeBlanc, R Birsner, A Shah, J Anderson, K D'Amato, R AF Lentzsch, S Rogers, M LeBlanc, R Birsner, A Shah, J Anderson, K D'Amato, R TI 3-amino-phthalimido-glutarimide (S-3APG) inhibits angiogenesis and growth in drug resistant multiple myeloma (NIM) in vivo. SO BLOOD LA English DT Meeting Abstract C1 Univ Med Ctr Berlin, Dept Hematol & Oncol, Robert Roessle Klin, Berlin, Germany. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1976 BP 473A EP 473A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101980 ER PT J AU Mitsiades, CS Mitsiades, N Poulaki, V Akiyama, M Chauhan, D Hideshima, T Treon, SP Anderson, KC AF Mitsiades, CS Mitsiades, N Poulaki, V Akiyama, M Chauhan, D Hideshima, T Treon, SP Anderson, KC TI IGF-1-Induced activation of NF-kappa B and upregulation of intracellular anti-apoptotic proteins in human multiple myeloma cells: Therapeutic implications. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1979 BP 473A EP 474A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134101983 ER PT J AU Gupta, D LeBlanc, R Catley, L Podar, K Lin, BK Tai, YT Chauhan, D Hideshima, T Anderson, KC AF Gupta, D LeBlanc, R Catley, L Podar, K Lin, BK Tai, YT Chauhan, D Hideshima, T Anderson, KC TI beta-Lapachone is safe and effective in Biege-Nude-Xid mouse xenograft model of human plasmacytoma. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 1980 BP 474A EP 474A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134101984 ER PT J AU Lin, TS Zahrieh, D Weller, E Alyea, ER Fisher, DC Gribben, JG Freedman, AS Schlossman, RL Lee, SJ Antin, JH Ritz, J Soiffer, RJ AF Lin, TS Zahrieh, D Weller, E Alyea, ER Fisher, DC Gribben, JG Freedman, AS Schlossman, RL Lee, SJ Antin, JH Ritz, J Soiffer, RJ TI Risk factors for CMV reactivation after T-cell depleted allogeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2007 BP 480A EP 481A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102011 ER PT J AU Alyea, EP Weller, E Schlossman, RL Webb, IJ Canning, CM Parikh, B Freeman, A Soiffer, RJ Ritz, J Anderson, KC AF Alyea, EP Weller, E Schlossman, RL Webb, IJ Canning, CM Parikh, B Freeman, A Soiffer, RJ Ritz, J Anderson, KC TI Comparison of autologous and allogeneic stem cell transplantation in patients with multiple myeloma (MM): Impact of graft versus myeloma (GVM) on relapse. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2014 BP 482A EP 483A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102018 ER PT J AU Lutskiy, MI Kenney, DM Rosen, FS Remold-O'Donnell, E AF Lutskiy, MI Kenney, DM Rosen, FS Remold-O'Donnell, E TI Wiskott-Aldrich syndrome in a female. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2109 BP 505A EP 506A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102114 ER PT J AU Vonderheide, RH Domchek, SM Hahn, WC George, DJ Stephans, KF Schultze, JL Nadler, LM AF Vonderheide, RH Domchek, SM Hahn, WC George, DJ Stephans, KF Schultze, JL Nadler, LM TI Vaccination of cancer patients against telomerase: A phase I study using peptide-pulsed dendritic cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2122 BP 508A EP 508A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102127 ER PT J AU Dias, SD Schneider, H Hu, H Rudd, CE AF Dias, SD Schneider, H Hu, H Rudd, CE TI The role of cytoplasmic YVKM motif in CTLA-4 inhibition of TCR signaling. SO BLOOD LA English DT Meeting Abstract C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Haematol, London, England. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol & Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2123 BP 509A EP 509A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102128 ER PT J AU Katsumoto, T Wardak, Z Kim, A Birnbaum, R Dranoff, G Clapp, DW Shannon, K AF Katsumoto, T Wardak, Z Kim, A Birnbaum, R Dranoff, G Clapp, DW Shannon, K TI GM-CSF is essential for efficient engraftment of Nf1 mutant and wild-type fetal liver cells in irradiated recipient mice. SO BLOOD LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Bloomington, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2292 BP 548A EP 548A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102299 ER PT J AU Roumiantsev, S Brasher, BB Van Etten, RA AF Roumiantsev, S Brasher, BB Van Etten, RA TI Mutational analysis of the regulatory function of the c-Abl Src homology 3 domain. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Enanta Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2395 BP 572A EP 572A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102402 ER PT J AU Wu, CJ Neuberg, D Chillemi, AC McLaughlin, SF Hochberg, EP Galinsky, I DeAngelo, D Antin, JH Soiffer, RJ Alyea, EP Capdeville, R Stone, RM Ritz, J AF Wu, CJ Neuberg, D Chillemi, AC McLaughlin, SF Hochberg, EP Galinsky, I DeAngelo, D Antin, JH Soiffer, RJ Alyea, EP Capdeville, R Stone, RM Ritz, J TI Quantitative monitoring of BCR/ABL transcripts during Gleevec (TM) therapy for chronic myelocytic leukemia (CML). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Novartis AG, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2576 BP 615A EP 615A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102583 ER PT J AU Sekeres, MA Stone, RM Zahrieh, D Neuberg, D Weeks, JC Lee, SJ AF Sekeres, MA Stone, RM Zahrieh, D Neuberg, D Weeks, JC Lee, SJ TI Depression and expectations for cure in older adults with advanced myelodysplastic syndrome (aMDS) or acute myeloid leukemia (AML) receiving intensive chemotherapy (IC) and non-intensive chemotherapy (NIC): Early results from a prospective study. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2619 BP 625A EP 625A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102626 ER PT J AU Flinn, IW Jemiai, Y Bennett, JM Falkson, CI Flynn, P Pundaleeka, S Stadtmauer, E Schnell, F Grever, M Tallman, MS Rowe, JM AF Flinn, IW Jemiai, Y Bennett, JM Falkson, CI Flynn, P Pundaleeka, S Stadtmauer, E Schnell, F Grever, M Tallman, MS Rowe, JM TI Fludarabine and cyclophosphamide achieves high complete response rate in patients with previously untreated chronic lymphocytic leukemia: ECOG 1997. SO BLOOD LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rochester, Rochester, NY 14627 USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. Metro Minnesota CCOP, St Louis Pk, MN USA. Joliet Oncol Hematol Assoc, Joliet, IL USA. Univ Penn, Philadelphia, PA 19104 USA. Med Ctr Cent Georgia, Macon, GA USA. Ohio State Univ, Sch Med, Columbus, OH 43210 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Rambam Med Ctr, Haifa, Israel. NR 0 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2649 BP 633A EP 633A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102656 ER PT J AU Mitsiades, CS Mitsiades, N Poulaki, V Hayashi, T Hideshima, T Podar, K LeBlanc, R Catley, L Tai, YT Chauhan, D Lin, B Schlossman, R Richardson, PG Munshi, N Treon, SP Anderson, KC AF Mitsiades, CS Mitsiades, N Poulaki, V Hayashi, T Hideshima, T Podar, K LeBlanc, R Catley, L Tai, YT Chauhan, D Lin, B Schlossman, R Richardson, PG Munshi, N Treon, SP Anderson, KC TI Receptor activator of nuclear factor-kappa B (RANK) ligand expression: In human multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2675 BP 638A EP 638A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102688 ER PT J AU Podar, K Tai, YT Lin, BK Kijima, T Salgia, R Narsimhan, R Sattler, M Gupta, D Chauhan, D Anderson, KC AF Podar, K Tai, YT Lin, BK Kijima, T Salgia, R Narsimhan, R Sattler, M Gupta, D Chauhan, D Anderson, KC TI VEGF-mediated multiple myeloma cell migration is associated with b1 integrin- and PI3-kinase-dependent PKCa activation. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2673 BP 638A EP 638A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102686 ER PT J AU Tai, YT Podar, K Gupta, D Lin, B Young, G Akiyama, M Anderson, KC AF Tai, YT Podar, K Gupta, D Lin, B Young, G Akiyama, M Anderson, KC TI CD40 activation induces p53-dependent vascular endothelial growth factor (VEGF) secretion in human multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2674 BP 638A EP 638A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102687 ER PT J AU Akiyama, M Hideshima, T Hayashi, T Tai, YT Mitsiades, CS Mitsiades, N Anderson, KC AF Akiyama, M Hideshima, T Hayashi, T Tai, YT Mitsiades, CS Mitsiades, N Anderson, KC TI IGF-1 induced telomerase activity and protects against apoptosis in multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2680 BP 639A EP 639A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102693 ER PT J AU Hideshima, T Nakamura, N Chauhan, D Anderson, KC AF Hideshima, T Nakamura, N Chauhan, D Anderson, KC TI Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2679 BP 639A EP 639A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102692 ER PT J AU Mitsiades, N Mitsiades, CS Poulaki, V Chauhan, D Anderson, KC Treon, SP AF Mitsiades, N Mitsiades, CS Poulaki, V Chauhan, D Anderson, KC Treon, SP TI Expression and regulation of soluble TRAIL (sTRAIL) in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2676 BP 639A EP 639A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102689 ER PT J AU LeBlanc, R Catley, L Hideshima, T von Schild, E Upton, T Anderson, KC AF LeBlanc, R Catley, L Hideshima, T von Schild, E Upton, T Anderson, KC TI A model for the in vitro and in vivo growth of multiple myeloma in the bone marrow microenvironment. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Cell Sci Therapeut Inc, Res & Ind BioProd Div, Woburn, MA USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2682 BP 640A EP 640A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102695 ER PT J AU Payvandi, F Wu, L Haley, M Gupta, D Zhang, L Schafer, P Muller, GW Chen, R Anderson, KC Stirling, DI AF Payvandi, F Wu, L Haley, M Gupta, D Zhang, L Schafer, P Muller, GW Chen, R Anderson, KC Stirling, DI TI Thaliomide analogs IMiDs inhibit expression of cyclooxygenase-2 in multiple myeloma cell line and LPS stimulated BMCS. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Celgene, Oncol, Warren, NJ USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2689 BP 641A EP 641A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102702 ER PT J AU Badros, A Tricot, G Toor, A Morris, C Barlogie, B Zangari, M Munshi, N Cottler-Fox, M AF Badros, A Tricot, G Toor, A Morris, C Barlogie, B Zangari, M Munshi, N Cottler-Fox, M TI ABO mismatch may affect engraftment in multiple myeloma (MM) patients (pts) receiving non-myeloablative conditioning. SO BLOOD LA English DT Meeting Abstract C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2714 BP 647A EP 647A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102727 ER PT J AU Panoskaltsis-Mortari, A Hermanson, JR Taras, EP Lees, CJ Charo, IF Rollins, BJ Blazar, BR AF Panoskaltsis-Mortari, A Hermanson, JR Taras, EP Lees, CJ Charo, IF Rollins, BJ Blazar, BR TI Lung injury and GVHD lethality occur independently of the expression of MCP-1 or its receptor, CCR2, on host cells. SO BLOOD LA English DT Meeting Abstract C1 Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Gladstone Inst, San Francisco, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2731 BP 651A EP 651A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102744 ER PT J AU Cahn, JY Klein, J Lee, SJ Cordonnier, JM Milpied, N Blaise, D Leblond, W Horowitz, MM Socie, G AF Cahn, JY Klein, J Lee, SJ Cordonnier, JM Milpied, N Blaise, D Leblond, W Horowitz, MM Socie, G TI Prospective evaluation of two acute graft versus host disease (AGVHD) grading systems: A joined Societe Francaise de Greffe de Moelle et Therapie Cellulaire (SFGM-TC), Dana Farber Cancer Institute (DFCI) and International Bone Marrow Transplant Registry (IBMTR) study. SO BLOOD LA English DT Meeting Abstract C1 IBMTR, Milwaukee, WI USA. DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2785 BP 664A EP 664A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102798 ER PT J AU Socie, G Klein, J Lee, SJ Milpied, N Blaise, D Leblond, V Horowitz, MM Cahn, JY AF Socie, G Klein, J Lee, SJ Milpied, N Blaise, D Leblond, V Horowitz, MM Cahn, JY TI Does time course of acute graft-versus-host disease (a.GVHD) have prognostic significance? A joint SFGM-TC, Dana Farber Cancer Institute (DFCI) & IBMTR study. SO BLOOD LA English DT Meeting Abstract C1 Hop St Louis, Paris, France. Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hop Hotel Dieu, Nantes, France. Inst J Paoli I Calmettes, F-13009 Marseille, France. IBMTR, Milwaukee, WI USA. Hop Jean Minjoz, F-25030 Besancon, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2784 BP 664A EP 664A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102797 ER PT J AU Spitzer, TR McAfee, SL Dey, BR Sackstein, R Colby, C Sachs, DH Sykes, M AF Spitzer, TR McAfee, SL Dey, BR Sackstein, R Colby, C Sachs, DH Sykes, M TI Durable progression free survival (PFS) following non-myeloablative bone marrow transplantation (BMT) for chemorefractory diffuse large B cell lymphoma (B-LCL). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2813 BP 672A EP 672A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102826 ER PT J AU Haluska, FG Goldberg, MA Linette, G Jonasch, E Hodi, FS Cunningham, CC Nemunaitis, J Webb, I Stowell, C Yang, SX AF Haluska, FG Goldberg, MA Linette, G Jonasch, E Hodi, FS Cunningham, CC Nemunaitis, J Webb, I Stowell, C Yang, SX TI Immunologic gene therapy: A phase I/II trial utilizing autologous dendritic cells transduced with gp100-and Melan A/MART-1-encoding adenoviruses in advanced melanoma. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. US Oncol Inc, Houston, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Genzyme Corp, Mol Oncol, Framingham, MA 01701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2903 BP 694A EP 695A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102916 ER PT J AU Liu, TX Rhodes, J Kanki, JP Hsu, K Radomska, HS Deng, M Piao, HY Zhou, Y Tenen, DG Zon, LI AF Liu, TX Rhodes, J Kanki, JP Hsu, K Radomska, HS Deng, M Piao, HY Zhou, Y Tenen, DG Zon, LI TI The cloning and characterization of zebrafish CCAAT/enhancer binding protein alpha. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2924 BP 699A EP 700A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102937 ER PT J AU Zhang, P Nelson, E Radomska, HS Iwasaki-Arai, J Akashi, K Friedman, AD Tenen, DG AF Zhang, P Nelson, E Radomska, HS Iwasaki-Arai, J Akashi, K Friedman, AD Tenen, DG TI Granulopoiesis by C/EBP alpha dependent and independent mechanisms. SO BLOOD LA English DT Meeting Abstract C1 Harvard Inst Med, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2922 BP 699A EP 699A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102935 ER PT J AU Appleman, LJ Nadler, LM Boussiotis, VA AF Appleman, LJ Nadler, LM Boussiotis, VA TI CD28 costimulation induces transcription of the recognition components. of the SCFskP2 ubiquitin ligase complex, which mediates degradation of P27(kip1). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2933 BP 701A EP 702A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102946 ER PT J AU Gilbert, GE Kaufman, RJ Ahmed, I Miao, HZ Pipe, S AF Gilbert, GE Kaufman, RJ Ahmed, I Miao, HZ Pipe, S TI Three hydrophobic amino acids in the factor VIIIC2 domain mediate interactions with phosholipid and with factor IXa. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Med, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2949 BP 705A EP 705A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102962 ER PT J AU Snyder, E Mintz, P Burks, S Haverstick, D Baril, L Dzik, W Purmal, A Beach, K AF Snyder, E Mintz, P Burks, S Haverstick, D Baril, L Dzik, W Purmal, A Beach, K TI Pathogen inactivated red blood cells using INACTINE (TM) technology demonstrate 24 hour post transfusion recovery equal to untreated red cells after 42 days of storage. SO BLOOD LA English DT Meeting Abstract C1 Univ Virginia, Hlth Syst, Charlottesville, VA USA. Yale New Haven Med Ctr, New Haven, CT 06504 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. VI Technol Inc, Watertown, MA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2965 BP 709A EP 710A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102978 ER PT J AU Sackstein, R Dimitroff, CJ Lee, JY Fuhlbrigge, RC Parmar, K Mauch, PM Sandmaier, BM AF Sackstein, R Dimitroff, CJ Lee, JY Fuhlbrigge, RC Parmar, K Mauch, PM Sandmaier, BM TI Homing and hematopoiesis: HCELL is the principal E-selectin and L-selectin ligand of human hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Skin Dis Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2967 BP 710A EP 710A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134102980 ER PT J AU Mikkola, HKA Fujiwara, Y Traver, D Schlaeger, TM Orkin, SH AF Mikkola, HKA Fujiwara, Y Traver, D Schlaeger, TM Orkin, SH TI CD41 marks the initiation of definitive hematopoiesis during mouse embryonic development. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 2973 BP 711A EP 712A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134102986 ER PT J AU Horning, SJ Glick, JH Kim, K Earle, J O'Connell, MJ Habermann, T Weller, E Gray, R AF Horning, SJ Glick, JH Kim, K Earle, J O'Connell, MJ Habermann, T Weller, E Gray, R TI Final report of E1484: CHOP v CHOP plus radiotherapy (RT) for limited stage diffuse aggressive lymphoma. SO BLOOD LA English DT Meeting Abstract C1 Stanford Univ, Stanford, CA 94305 USA. Univ Penn, Philadelphia, PA 19104 USA. Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3023 BP 724A EP 724A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103036 ER PT J AU Yang, XF Wu, CJ Chen, LY Chillemi, A McLaughlin, SF Canning, C Alyea, EP Soiffer, RJ Kantoff, P Dranoff, G Ritz, J AF Yang, XF Wu, CJ Chen, LY Chillemi, A McLaughlin, SF Canning, C Alyea, EP Soiffer, RJ Kantoff, P Dranoff, G Ritz, J TI CML28 is a broadly immunogenic tumor antigen associated with immune-induced remission of chronic myelogenous leukemia (CML). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3037 BP 728A EP 728A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103050 ER PT J AU Krackhardt, AM Witzens, M Zauls, AJ Barrett, P Chessia, M Gribben, JG AF Krackhardt, AM Witzens, M Zauls, AJ Barrett, P Chessia, M Gribben, JG TI Differential expression of newly identified CLL-associated antigenes: Ientification of a novel antigen with cancer-testis like expression pattern and genes with tumor-restricted splice variants. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3048 BP 731A EP 731A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103061 ER PT J AU Fonseca, R Harrington, D Blood, E Rue, M Oken, MM Dewald, GW Kyle, RA Van Wier, SA Henderson, KJ Bailey, RJ Greipp, PR AF Fonseca, R Harrington, D Blood, E Rue, M Oken, MM Dewald, GW Kyle, RA Van Wier, SA Henderson, KJ Bailey, RJ Greipp, PR CA ECOG Myeloma Grp TI A molecular classification of multiple myeloma (MM), based on cytogenetic abnormalities detected by interphase FISH, is powerful in identifying discrete groups of patients with dissimilar prognosis. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, ECOG Stat Ctr, Boston, MA 02115 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. NR 0 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3059 BP 733A EP 734A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103072 ER PT J AU Mitsiades, CS Mitsiades, N Poulaki, V Akiyama, M Treon, SP Anderson, KC AF Mitsiades, CS Mitsiades, N Poulaki, V Akiyama, M Treon, SP Anderson, KC TI High throughput global proteomic analysis of the signaling state of human multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3058 BP 733A EP 733A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103071 ER PT J AU Maziarz, RT Chauncey, TR Capdeville, R Druker, BJ Seelig, F AF Maziarz, RT Chauncey, TR Capdeville, R Druker, BJ Seelig, F TI Growth factor mobilization of CD34(+) PBSC in CML patients treated with imatinib (STI571). SO BLOOD LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Bone Marrow Transplant Program, Portland, OR 97201 USA. VA Puget Sound Hlth Care Syst, Bone Marrow Transplant Program, Seattle, WA USA. Novartis Pharmaceut, E Hanover, NJ USA. Oregon Hlth Sci Univ, Leukemia Program, Portland, OR 97201 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3078 BP 738A EP 738A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103091 ER PT J AU Loberiza, FR Rizzo, JD Bredeson, CN Antin, JH Horowitz, MM Weeks, JC Lee, SJ AF Loberiza, FR Rizzo, JD Bredeson, CN Antin, JH Horowitz, MM Weeks, JC Lee, SJ TI Depressive syndrome and early deaths following stem cell transplantation for hematologic diseases. SO BLOOD LA English DT Meeting Abstract C1 Med Coll Wisconsin, Hlth Policy Inst, IBMTR ABMTR, Milwaukee, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3091 BP 742A EP 742A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103104 ER PT J AU Neumann, CA Van Etten, RA AF Neumann, CA Van Etten, RA TI Hemolytic anemia and premature death in mice lacking Pag/Msp23, a novel member of the peroxiredoxin family of antioxidant enzymes. SO BLOOD 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 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3109 BP 746A EP 746A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103122 ER PT J AU Nisbet-Brown, E Olivieri, NF Giardina, PJ Grady, RW Sizer, K Sechaud, R Rosenkranz, G Alberti, D Nathan, DG AF Nisbet-Brown, E Olivieri, NF Giardina, PJ Grady, RW Sizer, K Sechaud, R Rosenkranz, G Alberti, D Nathan, DG TI ICL670A, a tridentate orally-active iron chelator, provides net negative iron balance and increased serum iron binding capacity in iron-overloaded patients with thalassemia. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Div Hematol, Boston, MA USA. Toronto Gen Hosp, Div Haematol, Toronto, ON, Canada. Weill Med Coll, Div Pediat Hematol, New York, NY USA. Novartis Pharmaceut Corp, Div Oncol Clin Res, E Hanover, NJ USA. Novartis Pharma AG, Dept Clin Pharmacol, Basel, Switzerland. Novartis Pharma AG, Clin Res, Oncol Business Unit, Basel, Switzerland. Novartis Farma SpA, Oncol Business Unit, Origgio, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3111 BP 747A EP 747A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103124 ER PT J AU Ni, H Sako, D Shaw, GD Schaub, RG Wagner, DD AF Ni, H Sako, D Shaw, GD Schaub, RG Wagner, DD TI Intravital microscopy of injured murine arterioles demonstrates that recombinant soluble GPIb-Ig chimeras inhibit thrombus formation in vivo. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Wyeth Ayerst Res, Genet Inst, Cambridge, MA 02140 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3138 BP 753A EP 753A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103151 ER PT J AU Ferrando, AA Neuberg, D Staunton, J Huard, C Raimondi, SC Behm, FG Downing, JR Gilliland, DG Golub, TR Pui, CH Lander, ES Look, AT AF Ferrando, AA Neuberg, D Staunton, J Huard, C Raimondi, SC Behm, FG Downing, JR Gilliland, DG Golub, TR Pui, CH Lander, ES Look, AT TI Prognostic classification of pediatric T-ALL using oligonucleotide microarrays. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Whitehead Inst, MIT Ctr Genome Res, Cambridge, MA 02142 USA. St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3163 BP 759A EP 760A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103176 ER PT J AU Stegmaier, K O'Malley, S Ross, K Bolk, S Blumenstiel, B Defelice, M Stockwell, B Golub, TR AF Stegmaier, K O'Malley, S Ross, K Bolk, S Blumenstiel, B Defelice, M Stockwell, B Golub, TR TI A chemical genomics approach to identifying leukemia differentiating agents. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead Inst, Cambridge, MA 02142 USA. MIT, Ctr Genome Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3169 BP 761A EP 761A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103182 ER PT J AU Cardoso, AA Keenan, TD Veiga, JP Tse, WT Sallan, SE Guinan, EC Nadler, LM AF Cardoso, AA Keenan, TD Veiga, JP Tse, WT Sallan, SE Guinan, EC Nadler, LM TI Leukemia milieu differentiates bone marrow mesenchymal stem cells into stromal-like cells that support leukemia cell survival. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3181 BP 764A EP 764A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103194 ER PT J AU LeBlanc, R Catley, L Hideshima, T Pien, CS Elliott, PJ Anderson, KC AF LeBlanc, R Catley, L Hideshima, T Pien, CS Elliott, PJ Anderson, KC TI Proteasome inhibitor PS-341 inhibits human multiple myeloma cell growth in a murine model. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Millenium Pharmaceut Inc, Cambridge, MA USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3222 BP 774A EP 774A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103235 ER PT J AU Richardson, PG Berenson, J Irwin, D Jagannath, S Traynor, A Rajkumar, V Alsina, M Kuter, D Srkalovic, G Siegel, D Barlogie, B Alexanian, R Orlowski, R Esseltine, D Kauffman, M Adams, J Schenkein, DP Anderson, KC AF Richardson, PG Berenson, J Irwin, D Jagannath, S Traynor, A Rajkumar, V Alsina, M Kuter, D Srkalovic, G Siegel, D Barlogie, B Alexanian, R Orlowski, R Esseltine, D Kauffman, M Adams, J Schenkein, DP Anderson, KC TI Phase II study of PS-341, a novel proteasome inhibitor, alone or in combination with dexamethasone in patients with multiple myeloma who have relapsed following front-line therapy and are refractory to their most recent therapy. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Alta Bates Canc Ctr, Berkeley, CA USA. St Vincents Canc Ctr, New York, NY USA. Northwestern Univ, Med Ctr, Chicago, IL 60611 USA. Mayo Clin, Rochester, MN USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Carol G Simon Canc Ctr, Morristown, NJ USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3223 BP 774A EP 774A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103236 ER PT J AU Mitsiades, N Mitsiades, CS Poulaki, V Akiyama, M Tai, YT Lin, BK Hayashi, T Catley, L Hideshima, T Chauhan, D Treon, SP Anderson, KC AF Mitsiades, N Mitsiades, CS Poulaki, V Akiyama, M Tai, YT Lin, BK Hayashi, T Catley, L Hideshima, T Chauhan, D Treon, SP Anderson, KC TI Apoptotic signaling induced by immunomodulatory thalidomide analogs (IMiDs) in human multiple myeloma cells: Therapeutic implications. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3224 BP 775A EP 775A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103237 ER PT J AU Richardson, PG Schlossman, RL Hideshima, T Davies, F LeBlanc, R Catley, L Doss, D Kelly, KA McKenney, M Mechlowicz, J Freeman, A Deocampo, R Rich, R Ryoo, J Chauhan, D Munshi, N Weller, E Thomas, S Zeldis, J Anderson, KC AF Richardson, PG Schlossman, RL Hideshima, T Davies, F LeBlanc, R Catley, L Doss, D Kelly, KA McKenney, M Mechlowicz, J Freeman, A Deocampo, R Rich, R Ryoo, J Chauhan, D Munshi, N Weller, E Thomas, S Zeldis, J Anderson, KC TI A phase 1 study of oral CC5013, an immunomodulatory thalidomide (Thal) derivative, in patients with relapsed and refractory multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Celgene Inc, Warren, NJ USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3225 BP 775A EP 775A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103238 ER PT J AU Kim, YM Mapara, MY Zhao, GL Sykes, M AF Kim, YM Mapara, MY Zhao, GL Sykes, M TI Lymphohematopoietic graft-versus-host reactions induced by DLI across various histocompatibility barriers. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. RI mapara, markus/A-2134-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3233 BP 777A EP 777A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103246 ER PT J AU Taniguchi, T Garcia-Higuera, I Lane, WS Kim, ST Xu, B Kastan, MB D'Andrea, AD AF Taniguchi, T Garcia-Higuera, I Lane, WS Kim, ST Xu, B Kastan, MB D'Andrea, AD TI Molecular interaction of the Fanconi Anemia (FA) and Ataxia Telangiectasia (AT) pathways. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Harvard Microchem & Proteom Anal Facil, Cambridge, MA USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RI Kim, Seong-Tae/A-9917-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3252 BP 782A EP 782A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103265 ER PT J AU Ince, N Harnisch, B Xu, Z Lee, SK Lieberman, J AF Ince, N Harnisch, B Xu, Z Lee, SK Lieberman, J TI Enhanced expression of the inhibitory receptor CD85j/ILT2 on antigen-specific CD8 T cells in HIV infection. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3266 BP 785A EP 786A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103279 ER PT J AU Houng, AK Polgar, J Reed, GL AF Houng, AK Polgar, J Reed, GL TI Sec1-syntaxin interactions in human platelets are governed by cell activation and regulate exocytosis. SO BLOOD 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 AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3274 BP 787A EP 787A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103287 ER PT J AU Zhang, P Iwasaki-Arai, J Lodie, T Fenyus, ML Lekstrom-Himes, J Foerster, I Akashi, K Tenen, DG AF Zhang, P Iwasaki-Arai, J Lodie, T Fenyus, ML Lekstrom-Himes, J Foerster, I Akashi, K Tenen, DG TI C/EBP alpha deficiency blocks granulocytic differentiation at the common myeloid progenitor stage in both adult and fetal liver myelopoiesis. SO BLOOD LA English DT Meeting Abstract C1 Harvard Inst Med, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. NIAID, LHD, Bethesda, MD USA. Tech Univ Munich, Inst Microbiol, Munich, Germany. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3297 BP 792A EP 793A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103310 ER PT J AU Cantor, AB Chang, AN Orkin, SH AF Cantor, AB Chang, AN Orkin, SH TI Plasticity of mature hematopoietic cells: Ectopic expression of the GATA cofactor FOG-1 reprograms primary mast cells into erythroid and megakaryocytic cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3298 BP 793A EP 793A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103311 ER PT J AU Chang, AN Cantor, AB Crispino, JD Fujiwara, Y Orkin, SH AF Chang, AN Cantor, AB Crispino, JD Fujiwara, Y Orkin, SH TI The essential role of FOG-1 in early megakaryopoiesis requires an interaction with either GATA-1 or GATA-2. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3301 BP 793A EP 794A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103314 ER PT J AU Armstrong, SA Staunton, JE Mabon, ME Silverman, LB Pieters, R den Boer, ML Minden, MD Sallan, SE Lander, ES Golub, TR Korsmeyer, SJ AF Armstrong, SA Staunton, JE Mabon, ME Silverman, LB Pieters, R den Boer, ML Minden, MD Sallan, SE Lander, ES Golub, TR Korsmeyer, SJ TI The MLL dependent gene expression profile: Characterization of a unique leukemia and identification of a potential molecular therapeutic target. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Sophia Childrens Univ Hosp, Rotterdam, Netherlands. Univ Toronto, Toronto, ON, Canada. Whitehead MIT Ctr Genome Res, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3327 BP 800A EP 800A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103340 ER PT J AU Okuda, K Sato, Y Griffin, JD AF Okuda, K Sato, Y Griffin, JD TI The TEL/ARG leukemia oncogene promotes viability and hyper-responsiveness to hematopoietic growth factors. SO BLOOD LA English DT Meeting Abstract C1 Int Med Ctr, Tokyo, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3337 BP 802A EP 802A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103350 ER PT J AU Krackhardt, AM Witzens, M Zauls, AJ Barrett, P Gribben, JG AF Krackhardt, AM Witzens, M Zauls, AJ Barrett, P Gribben, JG TI Identification of novel tumor-associated antigens in CLL - Implications for immunotherapy in CLL SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3356 BP 807A EP 807A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103369 ER PT J AU Lentzsch, S Chatterje, M Hideshima, T Podar, K Anderson, KC Mapara, MY Dorken, B Bargou, R AF Lentzsch, S Chatterje, M Hideshima, T Podar, K Anderson, KC Mapara, MY Dorken, B Bargou, R TI The phosphatidylinositol-3-kinase/Akt kinase pathway plays an important role in cytokine-dependent survival of multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 Univ Med Ctr, Charite CCB, Berlin, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI mapara, markus/A-2134-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3367 BP 810A EP 810A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103380 ER PT J AU Lee, SJ Zahrieh, D Weller, E Antin, JH Alyea, EP Ritz, J Soiffer, RJ AF Lee, SJ Zahrieh, D Weller, E Antin, JH Alyea, EP Ritz, J Soiffer, RJ TI Similar clinical outcomes and quality of life, but lower costs associated with T-cell depleted unrelated donor bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3381 BP 813A EP 814A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103394 ER PT J AU Tzachanis, D Freeman, GJ Hirano, N van Puijenbroek, AAFL Delfs, MW Berezovskaya, A Nadler, LM Boussiotis, VA AF Tzachanis, D Freeman, GJ Hirano, N van Puijenbroek, AAFL Delfs, MW Berezovskaya, A Nadler, LM Boussiotis, VA TI Tob increases the threshold of T cell activation and functions as a negative regulator of cell cycle progression and cytokine transcription. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3399 BP 818A EP 818A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103412 ER PT J AU Marshall, DJ Anosova, N Bagley, J Kinchsular, J Hyunh, V Scadden, DT Rosenzweig, M AF Marshall, DJ Anosova, N Bagley, J Kinchsular, J Hyunh, V Scadden, DT Rosenzweig, M TI Engineering a thymus for efficient production of human T cells. SO BLOOD LA English DT Meeting Abstract C1 Cell Sci Therapeut, Woburn, MA USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3408 BP 820A EP 820A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103421 ER PT J AU Freedman, S Sun, ZYJ Poy, F Kung, AL Livingston, DM Wagner, G Eck, MJ AF Freedman, S Sun, ZYJ Poy, F Kung, AL Livingston, DM Wagner, G Eck, MJ TI Novel mechanism for tumor inhibition revealed by the structure of the HIF-1 alpha/p300 complex. SO BLOOD LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Div Hematol & Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3449 BP 830A EP 830A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103462 ER PT J AU Wu, LZ Kobayashi, K Griffin, JD AF Wu, LZ Kobayashi, K Griffin, JD TI Identification of a family of transcriptional co-activators for mammalian Notch receptors. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3451 BP 830A EP 830A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103464 ER PT J AU Martinez, RV Widlund, H El-Hayek, K Ladd, C Sasaki, K Fisher, DE Ozato, K Golub, TR AF Martinez, RV Widlund, H El-Hayek, K Ladd, C Sasaki, K Fisher, DE Ozato, K Golub, TR TI The ETs protein TEL regulates the interferon gamma transcriptional response via ICSBP. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead MIT Ctr Genome Res, Cambridge, MA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3460 BP 833A EP 833A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103473 ER PT J AU Kang, H Griffin, JD AF Kang, H Griffin, JD TI Mechanisms of activation of FLT3 kinase activity by internal tandem duplications of the juxtamembrane domain and point mutations at D835. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3478 BP 837A EP 837A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103491 ER PT J AU Tricot, G Siegel, E Langmaid, C Munshi, N Anaissie, E Fassas, A Desikan, R Badros, A Zangari, M Barlogie, B AF Tricot, G Siegel, E Langmaid, C Munshi, N Anaissie, E Fassas, A Desikan, R Badros, A Zangari, M Barlogie, B TI Angiochemotherapy (ACT) for multiple myeloma (MM) with DT-PACE results in a high response rate, but in contrast to tandem transplants with melphalan does not affect durable disease control. SO BLOOD LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincent Comprehens Canc Ctr, New York, NY USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3531 BP 850A EP 850A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103544 ER PT J AU Richardson, PG Warren, DL Momtaz, P Soiffer, R Antin, JH Spitzer, T Avigan, D Wei, LJ Jin, Z Rifai, N Bradwin, G Vredenburgh, J Kurtzberg, J Martin, PL Vogelsang, G Arai, S Chen, A McDonald, GB Murray, K Iacobelli, M Guinan, EC AF Richardson, PG Warren, DL Momtaz, P Soiffer, R Antin, JH Spitzer, T Avigan, D Wei, LJ Jin, Z Rifai, N Bradwin, G Vredenburgh, J Kurtzberg, J Martin, PL Vogelsang, G Arai, S Chen, A McDonald, GB Murray, K Iacobelli, M Guinan, EC TI Multi-institutional phase II, randomized dose finding study of defibrotide (DF) in patients (pts) with severe veno-occlusive disease (VOD) and multi-system organ failure (MOF) post stem cell transplantation (SCT): Promising response rate without significant toxicity in a high risk population. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Hosp, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Columbia Univ, New York, NY 10027 USA. Duke Univ, Med Ctr, Durham, NC USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Crinos Italy SpA, Como, Italy. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3544 BP 853A EP 853A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103557 ER PT J AU Hochberg, EP Miklos, DB Mclaughlin, S Mattes-Ritz, A Scola, A Neuberg, D Alyea, E Soiffer, R Antin, J Ritz, J AF Hochberg, EP Miklos, DB Mclaughlin, S Mattes-Ritz, A Scola, A Neuberg, D Alyea, E Soiffer, R Antin, J Ritz, J TI A novel rapid single nucleotide polymorphism (SNP) based method for assessment of hematopoietic chimerism after allogeneic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3549 BP 854A EP 855A PN 1 PG 2 WC Hematology SC Hematology GA 491WY UT WOS:000172134103562 ER PT J AU Zorn, E Wang, KS Hochberg, EP Canning, C Alyea, EP Soiffer, RJ Ritz, J AF Zorn, E Wang, KS Hochberg, EP Canning, C Alyea, EP Soiffer, RJ Ritz, J TI CD4 positive donor lymphocyte infusion induces a CD8 positive T cell response directed against recipient hematopoietic cells in patients treated for relapsed CML after allogeneic bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3548 BP 854A EP 854A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103561 ER PT J AU Soiffer, RJ Alyea, EP Canning, C Hochberg, E Zahrieh, D Parikh, B Webb, I Antin, J Ritz, J AF Soiffer, RJ Alyea, EP Canning, C Hochberg, E Zahrieh, D Parikh, B Webb, I Antin, J Ritz, J TI A randomized trial of CD8+T cell depletion to prevent graft-vs-host disease (GVHD) associated with donor lymphocyte infusions. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3554 BP 856A EP 856A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103567 ER PT J AU Antin, JH Lee, SJ Neuberg, D Alyea, E Ritz, J Soiffer, RJ AF Antin, JH Lee, SJ Neuberg, D Alyea, E Ritz, J Soiffer, RJ TI Sirolimus (RAP), tacrolimus (FK), and low dose methotrexate (MTX) for GVHD prophylaxis in mismatched related donor or unrelated donor transplantation. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2001 VL 98 IS 11 MA 3559 BP 857A EP 857A PN 1 PG 1 WC Hematology SC Hematology GA 491WY UT WOS:000172134103572 ER PT J AU Moody, AM Chui, D Reche, PA Priatel, JJ Marth, JD Reinherz, EL AF Moody, AM Chui, D Reche, PA Priatel, JJ Marth, JD Reinherz, EL TI Developmentally regulated glycosylation of the CD8 alpha beta coreceptor stalk modulates ligand binding SO CELL LA English DT Article ID CD8 BETA-CHAIN; TISSUE-SPECIFIC EXPRESSION; O-GLYCAN BIOSYNTHESIS; T-CELL ACTIVATION; NEGATIVE SELECTION; PEANUT AGGLUTININ; FUNCTIONAL-ANALYSIS; POSITIVE SELECTION; CRYSTAL-STRUCTURE; ALPHA-3 DOMAIN AB The functional consequences of glycan structural changes associated with cellular differentiation are ill defined. Herein, we investigate the role of glycan adducts to the O-glycosylated polypeptide stalk tethering the CD8 alpha beta coreceptor to the thymocyte surface. We show that immature CD4(+)CD8(+) double-positive thymocytes bind MHCI tetramers more avidly than mature CD8 single-positive thymocytes, and that this differential binding is governed by developmentally programmed O-glycan modification controlled by the ST3Gal-1 sialyltransferase. ST3Gal-1 induction and attendant core 1 sialic acid addition to CD8 beta on mature thymocytes decreases CD8 alpha beta -MHCI avidity by altering CD8 alpha beta domain-domain association and/or orientation. Hence, glycans on the CD8 beta stalk appear to modulate the ability of the distal binding surface of the dimeric, CD8 globular head domains to clamp MHCI. C1 Harvard Univ, Sch Med, Dept Med,Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Lab Immunobiol, Boston, MA 02115 USA. Univ Calif San Diego, Dept Cellular & Mol Med, Glycobiol Res & Training Ctr, Howard Hughes Med Inst, La Jolla, CA 92093 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dept Med,Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Lab Immunobiol, Boston, MA 02115 USA. RI Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 FU NHLBI NIH HHS [HL57345]; NIAID NIH HHS [AI19807, AI45022] NR 55 TC 150 Z9 151 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 16 PY 2001 VL 107 IS 4 BP 501 EP 512 DI 10.1016/S0092-8674(01)00577-3 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 494GG UT WOS:000172272900010 PM 11719190 ER PT J AU Kato, T Kure, T Chang, JH Gabison, EE Itoh, T Itohara, S Azar, DT AF Kato, T Kure, T Chang, JH Gabison, EE Itoh, T Itohara, S Azar, DT TI Diminished corneal angiogenesis in gelatinase A-deficient mice SO FEBS LETTERS LA English DT Article DE gelatinase A; matrix metalloproteinase; cornea; angiogenesis; knockout mouse ID MATRIX METALLOPROTEINASES; MODEL; NEOVASCULARIZATION; KERATECTOMY; PROGRESSION; INHIBITOR AB The goal of the present study was to define the role of gelatinase A in angiogenesis. We performed corneal micropocket assays in gelatinase A-deficient mice and their age-matched wildtype littermates. The corneal neovascular area in gelatinase A-deficient mice (0.15 +/- 0.14 mm(2)) was significantly less than that of wild-type littermates; (0.53 +/- 0.35 mm(2) - P < 0.01). Similarly, aortic ring assays showed significant reduction of endothelial outgrowth in gelatinase A-deficient mice (0.26 +/- 0.14 mm(2)) as compared to wild-type littermates (0.44 +/- 0.06 mm(2); P < 0.05). These results suggest that gelatinase A may play an important role in the regulation of corneal angiogenesis. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Shionogi & Co Ltd, Discovery Res Labs, Osaka, Japan. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Schepens Eye Res Inst, 243 Charles St, Boston, MA 02114 USA. RI Itohara, Shigeyoshi/I-8769-2012 OI Itohara, Shigeyoshi/0000-0002-2410-9989 FU NEI NIH HHS [EY10101] NR 14 TC 93 Z9 97 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 16 PY 2001 VL 508 IS 2 BP 187 EP 190 DI 10.1016/S0014-5793(01)02897-6 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 495PT UT WOS:000172350100005 PM 11718713 ER PT J AU Kim, M Chen, B Hussey, RE Chishti, Y Montefiori, D Hoxie, JA Byron, O Campbell, G Harrison, SC Reinherz, EL AF Kim, M Chen, B Hussey, RE Chishti, Y Montefiori, D Hoxie, JA Byron, O Campbell, G Harrison, SC Reinherz, EL TI The stoichiometry of trimeric SIV glycoprotein interaction with CD4 differs from that of anti-envelope antibody Fab fragments SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODIES; SOLUBLE CD4; SYNERGISTIC NEUTRALIZATION; ATOMIC-STRUCTURE; HTLV-III/LAV; HIV-1 GP41; RECEPTOR-BINDING; CD4-BINDING SITE; GP120 MOLECULES AB Human and simian immunodeficiency viruses infect host lymphoid cells by binding CD4 molecules via their gp160 envelope glycoproteins. Biochemical studies on recombinant SIVmac32H (pJ5) envelope ectodomain gp140 precursor protein show that the envelope is a trimer. Using size exclusion chromatography, quantitative amino acid analysis, analytical ultracentrifugation, and CD4-based competition assay, we demonstrate that the stoichiometry of CD4 receptor-oligomeric envelope interaction is 1:1. By contrast, Fab fragments of both neutralizing and non-neutralizing monoclonal antibodies bind at a 3:1 ratio. Thus, despite displaying equivalent CD4 binding sites on each of the three gp140 protomers within an uncleaved trimer, only one site binds the soluble 4-domain human CD4 extracellular segment. The anti-cooperativity and the faster k(off) of gp140 trimer:CD4 versus gp120 monomer:CD4 interaction suggest that CD4-induced conformational change is impeded in the intact envelope. The implications of these findings for immunity against human immunodeficiency virus and simian immunodeficiency virus are discussed. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Mol Med Lab, Boston, MA 02115 USA. Duke Univ, Sch Med, Dept Surg, Durham, NC 27710 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Glasgow, Inst Biomed & Life Sci, Div Infect & Immun, Glasgow G12 8QQ, Lanark, Scotland. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI43649, AI85343] NR 70 TC 27 Z9 27 U1 0 U2 4 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 NOV 16 PY 2001 VL 276 IS 46 BP 42667 EP 42676 DI 10.1074/jbc.M104166200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300006 PM 11544255 ER PT J AU Gensure, RC Carter, PH Petroni, BD Juppner, H Gardella, TJ AF Gensure, RC Carter, PH Petroni, BD Juppner, H Gardella, TJ TI Identification of determinants of inverse agonism in a constitutively active parathyroid hormone/parathyroid hormone-related peptide receptor by photoaffinity cross-linking and mutational analysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID JANSENS METAPHYSEAL CHONDRODYSPLASIA; PTH-RELATED PEPTIDE; EXTRACELLULAR LOOP; TERMINAL REGION; WILD-TYPE; ANTAGONISTS; BINDING; ACTIVATION; PROTEINS; ANALOG AB We have investigated receptor structural components responsible for ligand-dependent inverse agonism in a constitutively active mutant of the human parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor type 1 (hP1R). This mutant receptor, hP1R-H223R (hP1R(CAM-HR)), was originally identified in Jansen's chondrodysplasia and is altered in transmembrane domain (TM) 2. We utilized the PTHrP analog, [Bpa(2), Ile(5),Trp(23),Tyr(36)]PTHrP-(1-36)-amide (Bpa(2)-PTHrP- (1-36)), which has valine 2 replaced by p-benzoyl-L-phenylalanine (Bpa); this substitution renders the peptide a photoreactive inverse agonist at hP1R(CAM-HR). This analog cross-linked to hP1R(CAM-HR) at two contiguous receptor regions as follows: the principal cross-link site (site A) was between receptor residues Pro(415)-Met(441), spanning the TM6/extracellular loop three boundary; the second crosslink site (site B) was within the TM4/TM5 region. Within the site A interval, substitution of Met(425) to Leu converted Bpa(2)-PTHrP-(1-36) from an inverse agonist to a weak partial agonist; this conversion was accompanied by a relative shift of cross-linking from site A to site B. The functional effect of the M425L mutation was specific for Bpa(2)-containing analogs, as inverse agonism of Bpa(2)-PTH-(1-34) was similarly eliminated, whereas inverse agonism of [Leu(11), D-Trp(12)]PTHrP-(5-36) was not affected. Overall, our data indicate that interactions between residue 2 of the ligand and the extracellular end of TM6 of the hP1R play an important role in modulating the conversion between active and inactive receptor states. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK11794, 1F32DK10034-01] NR 45 TC 25 Z9 25 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 NOV 16 PY 2001 VL 276 IS 46 BP 42692 EP 42699 DI 10.1074/jbc.M106215200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300009 PM 11553625 ER PT J AU Beresford, PJ Zhang, D Oh, DY Fan, ZS Greer, EL Russo, ML Jaju, M Lieberman, J AF Beresford, PJ Zhang, D Oh, DY Fan, ZS Greer, EL Russo, ML Jaju, M Lieberman, J TI Granzyme A activates an endoplasmic reticulum-associated caspase-independent nuclease to induce single-stranded DNA nicks SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN PHOSPHATASE 2A; CHROMATIN-LIKE STRUCTURE; FACTOR-I; CELL-DEATH; GRANULE-EXOCYTOSIS; MEDIATED APOPTOSIS; ADENOVIRUS GENOME; INHIBITOR; LEUKEMIA; TEMPLATE AB The cytotoxic T lymphocyte protease granzyme A (GzmA) initiates a novel caspase-independent cell death pathway characterized by single-stranded DNA nicking. The previously identified GzmA substrate SET is in a multimeric 270-420-kDa endoplasmic reticulum-associated complex that also contains the tumor suppressor protein pp32. GzmA cleaved the nucleosome assembly protein SET after Lys(176) and disrupted its nucleosome assembly activity. The purified SET complex required only GzmA to reconstitute single-stranded DNA nicking in isolated nuclei. DNA nicking occurred independently of caspase activation. The SET complex contains a 25-kDa Mg2+-dependent nuclease that degrades calf thymus DNA and plasmid DNA. Thus, GzmA activates a DNase (GzmA-activated DNase) within the SET complex to produce a novel form of DNA damage during cytotoxic T lymphocyte-mediated death. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI45587] NR 47 TC 112 Z9 118 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 NOV 16 PY 2001 VL 276 IS 46 BP 43285 EP 43293 DI 10.1074/jbc.M108137200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300085 PM 11555662 ER PT J AU Mao, YW Xiang, H Wang, J Korsmeyer, S Reddan, J Li, DWC AF Mao, YW Xiang, H Wang, J Korsmeyer, S Reddan, J Li, DWC TI Human bcl-2 gene attenuates the ability of rabbit lens epithelial cells against H2O2-induced apoptosis through down-regulation of the alpha B-crystallin gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; CAMPTOTHECIN-INDUCED APOPTOSIS; A-CRYSTALLIN; FIBER DIFFERENTIATION; NUCLEOTIDE-SEQUENCE; OXIDATIVE DAMAGE; DEATH; EXPRESSION; PROTEIN; INHIBITION AB It is well established that the proto-oncogene, bcl-2, can prevent apoptosis induced by a variety of factors. Regarding the mechanism by which BCL-2 prevents cell death, one theory suggests that it acts by protecting cells from oxidative stress. In the lens system, oxidative stress-induced apoptosis is implicated in cataractogenesis. To explore the possibility of anti-apoptotic gene therapy development for cataract prevention and also to further test the anti-oxidative stress theory of BCL-2 action, we have introduced the human bcl-2 gene into an immortalized rabbit lens epithelial cell line, N/N1003A. The stable expression clones of both vector- and bcl-2-transfected cells have been established. Treatment of the two cell lines With H2O2 revealed that bcl-2-transfected cells were less capable of detoxifying H2O2 than the control cells. Moreover, bcl-2-transfected cells are more susceptible to H2O2-induced apoptosis. To explore why bcl-2-transfected cells have reduced resistance to H2O2-induced apoptosis, we examined the expression patterns of several relevant genes and found that expression of the alphaB-crystallin gene was distinctly downregulated in bcl-2-transfected cells compared with that in vector-transfected cells. This down-regulation was specific because a substantial inhibition of BCL-2 expression through antisense bcl-2 RNA significantly restored the level of alphaB-crystallin and, moreover, enhanced the ability of the bcl-2-transfected cells against H2O2-induced apoptosis. Introduction of a mouse alphaB-crystallin gene into bcl-2-transfected cells also counteracted the BCL-2 effects. Down-regulation of alphaB-crystallin gene was largely derived from changed lens epithelial cell-derived growth factor activity. Besides, alphaB-crystallin prevents apoptosis through interaction with procaspase-3 and partially processed procaspase-3 to prevent caspase-3 activation. Together, our results reveal that BCL-2 can regulate gene expression in rabbit lens epithelial cells. Through down-regulation of the alphaB-crystallin gene, BCL-2 attenuates the ability of rabbit lens epithelial cells against H2O2-induced apoptosis. C1 Univ Med & Dent New Jersey, Sch Osteopath Med, Ctr Sci, Dept Mol Biol, Stratford, NJ 08084 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Oakland Univ, Dept Biol Sci, Rochester, MI 48309 USA. RP Li, DWC (reprint author), Univ Med & Dent New Jersey, Sch Osteopath Med, Ctr Sci, Dept Mol Biol, Rm 347,2 Med Ctr Dr, Stratford, NJ 08084 USA. OI 向, 华/0000-0003-0369-1225 FU NEI NIH HHS [R29 EY011372] NR 72 TC 82 Z9 86 U1 0 U2 6 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 NOV 16 PY 2001 VL 276 IS 46 BP 43435 EP 43445 DI 10.1074/jbc.M102195200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 492LF UT WOS:000172169300104 PM 11546795 ER PT J AU Suit, HD Withers, HR AF Suit, HD Withers, HR TI Endothelial cells and radiation gastrointestinal syndrome SO SCIENCE LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90095 USA. RP Suit, HD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 4 TC 3 Z9 3 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 16 PY 2001 VL 294 IS 5546 BP 1411A EP 1411A DI 10.1126/science.294.5546.1411a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 493TX UT WOS:000172240500001 ER PT J AU Sloan, KL Sales, AE Willems, JP Every, NR Martin, GV Sun, HL Pineros, S Sharp, N AF Sloan, KL Sales, AE Willems, JP Every, NR Martin, GV Sun, HL Pineros, S Sharp, N TI Frequency of serum low-density lipoprotein cholesterol measurement and frequency of results <= 100 mg/dl among patients who had coronary events (Northwest VA Network study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LIPID-LOWERING THERAPY; ARTERY DISEASE; HEART-DISEASE; UNITED-STATES; ADHERENCE; GOALS AB This population-based, cross-sectional analysis targeted all veterans with coronary heart disease (CHD) who were active patients in primary care or cardiology clinics in the Veterans Health Administration Northwest Network from July 1998 to June 1999. We report guideline compliance rates, including whether low-density lipoprotein (LDL) was measured, and if measured, whether the LDL was less than or equal to 100 mg/dl. In addition, we utilized multivariate logistic regression to determine patient characteristics associated with LDL measurements and levels. Of 13,891 active patients with CHD, 5,552 (40.0%) did not have a current LDL measurement. Of those with LDL measurements, 39.1% were at the LDL goal of less than or equal to 100 mg/dl, whereas 26.5% had LDL greater than or equal to 130 mg/dl. Male gender, younger age, history of angioplasty or coronary artery bypass grafting, current hypertension, diabetes mellitus, and angina pectoris were associated with increased likelihood of LDL measurement. Older age and current diabetes and angina were associated with increased likelihood of LDL being less than or equal to 100 mg/dl, if measured. Although these rates of guideline adherence in the CHD population compare well to previously published results, they continue to be unacceptably low for optimal clinical outcomes. Attention to both LDL measurement and treatment (if elevated) is warranted. (C) 2001 by Excerpta Medica, Inc. C1 VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Div Cardiol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA 98108 USA. Psychiat & Behav Sci Serv, Seattle, WA USA. Psychiat & Behav Hlth Serv, Seattle, WA USA. Robert Wood Johnson Clin Scholars Program, Seattle, WA USA. RP Sloan, KL (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv, 116-DDTP, Seattle, WA 98108 USA. OI Sales, Anne/0000-0001-9360-3334 NR 10 TC 19 Z9 19 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2001 VL 88 IS 10 BP 1143 EP 1146 DI 10.1016/S0002-9149(01)02050-1 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 496TH UT WOS:000172412300012 PM 11703960 ER PT J AU Park, WY Goodman, RB Steinberg, KP Ruzinski, JT Radella, F Park, DR Pugin, J Skerrett, SJ Hudson, LD Martin, TR AF Park, WY Goodman, RB Steinberg, KP Ruzinski, JT Radella, F Park, DR Pugin, J Skerrett, SJ Hudson, LD Martin, TR TI Cytokine balance in the lungs of patients with acute respiratory distress syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; cytokine receptors; cytokines; IL-1; TNF ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; SOLUBLE IL-6 RECEPTOR; INFLAMMATORY CYTOKINES; HUMAN-MONOCYTES; FACTOR-ALPHA; BRONCHOALVEOLAR; FLUID; ARDS; AUTOANTIBODIES AB Acute respiratory distress syndrome (ARDS) involves an Intense Inflammatory response in the lungs, with accumulation of both pro- and antiinflammatory cytokines in bronchoalveolar lavage fluid (BALF). Our goal was to determine how the balance between pro- and antiinflammatory mediators in the lungs changes before and after the onset of ARDS. We identified 23 patients at risk for ARDS and 46 with established ARDS and performed serial bronchoalveolar lavage (BAL). We used immunoassays to measure tumor necrosis factor alpha (TNF-alpha) and soluble TNF-alpha receptors I and II; interleukin 1 beta (IL-1 beta), IL-1 beta receptor antagonist, and soluble IL-1 receptor II; IL-6 and soluble IL-6 receptor; and IL-10. We used sensitive bioassays to measure net TNF-alpha, IL-1 beta and IL-6 activity. Although individual cytokines increased before and after onset of ARDS, greater increases occurred in cognate receptors and/or antagonists, so that molar ratios of agonists/antagonists declined dramatically at the onset of ARDS. The molar ratios remained low for 7 d or longer, limiting the activity of soluble IL-1 beta and TNF-alpha in the lungs at the onset of ARDS. This significant antiinflammatory response early in ARDS may provide a key mechanism for limiting the net inflammatory response in the lungs. C1 VA Puget Sound Hlth Care Syst, Harborview Med Ctr, Sect Pulm Crit Care Med, Med Res Serv, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Univ Geneva, Med Ctr, Dept Med Intens Care, CH-1211 Geneva, Switzerland. RP Martin, TR (reprint author), Seattle VA Med Ctr, Pulm Res Labs, 151L,1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL30542]; NIAID NIH HHS [AI29103] NR 47 TC 264 Z9 307 U1 0 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2001 VL 164 IS 10 BP 1896 EP 1903 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 502TK UT WOS:000172758700029 PM 11734443 ER PT J AU Gurubhagavatula, I Maislin, G Pack, AI AF Gurubhagavatula, I Maislin, G Pack, AI TI An algorithm to stratify sleep apnea risk in a sleep disorders clinic population SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE obstructive sleep apnea; risk stratification; polysomnography; nocturnal pulse oximetry; questionnaire ID 2-STAGE SCREENING-PROCEDURE; HYPOPNEA SYNDROME; HEALTH; DIAGNOSIS; POLYSOMNOGRAPHY; COMMUNITY; VALIDITY; OXIMETRY; QUESTIONNAIRE; HYPERTENSION AB Obstructive sleep apnea may lead to complications if not identified and treated. Polysomnography is the diagnostic standard, but is often inaccessible due to bed shortages. A system that facilitates prioritization of patients requiring sleep studies would thus be useful. We retrospectively compared the accuracy of a two-stage risk-stratification algorithm for sleep apnea using questionnaire plus nocturnal pulse oximetry against using polysomnography to identify patients without apnea (Objective 1) and those with severe apnea (Objective 2). Patients were those referred to a university-based sleep disorders clinic due to suspicion of sleep apnea. Subjects completed a sleep apnea symptom questionnaire, and underwent oximetry and two-night polysomnography. We used bootstrap methodology to maximize sensitivity of our model for Objective I and specificity for Objective 2. We calculated sensitivity, specificity, positive and negative predictive values, and rate of misclassification error of the two-stage risk-stratification algorithm for each of our two objectives. The model identified cases of sleep apnea with 95% sensitivity and severe apnea with 97% specificity. It excluded only 8% of patients from sleep studies, but prioritized up to 23% of subjects to receive in-laboratory studies. Among sleep disorders clinic referrals, a two-stage risk-stratification algorithm using questionnaire and nocturnal pulse oximetry excluded few patients from sleep studies, but identified a larger proportion of patients who should receive early testing because of their likelihood of having severe disease. C1 Univ Penn, Ctr Sleep & Resp Neurobiol, Div Pulm & Crit Care, Dept Med,Med Ctr, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Pulm & Crit Care Sect, Philadelphia, PA USA. RP Gurubhagavatula, I (reprint author), Hosp Univ Penn, Ctr Sleep & Resp Neurobiol, 9th Floor,Maloney Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. FU CCR NIH HHS [CRC-RR-00040]; NHLBI NIH HHS [T32 HL007713, HL-07713, HL-42236] NR 41 TC 52 Z9 52 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2001 VL 164 IS 10 BP 1904 EP 1909 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 502TK UT WOS:000172758700030 PM 11734444 ER PT J AU Yabu, T Kishi, S Okazaki, T Yamashita, M AF Yabu, T Kishi, S Okazaki, T Yamashita, M TI Characterization of zebrafish caspase-3 and induction of apoptosis through ceramide generation in fish fathead minnow tailbud cells and zebrafish embryo SO BIOCHEMICAL JOURNAL LA English DT Article DE caspase inhibitor; cDNA cloning; development; maternal factor ID ICE-LIKE PROTEASE; DEATH GENE CED-3; INTERLEUKIN-1-BETA-CONVERTING ENZYME; ICE/CED-3 PROTEASE; CONVERTING-ENZYME; HEAT-SHOCK; ACTIVATION; MEDIATOR; FAMILY; CPP32 AB Caspase-3 was cloned from zebrafish embryos and its properties were characterized to identify the biological implications of caspase in embryogenesis and apoptosis in zebrafish, which is a model organism in vertebrate developmental biology and genetics. The predicted amino acid sequence, totalling 282 amino acid residues, consisted of the prodomain and large and small subunits. Phylogenetic analysis showed that the cloned zebrafish caspase was a member of the caspase-3 subfamily with approx. 60% identity with caspase-3 from Xenopus, chicken and mammals. In addition, recombinant zebrafish caspase hydrolysed acetyl-Asp-Glu-Val-Asp-4-methyl-coumaryl-7-ainide, and exhibited similar substrate specificity to the mammalian caspase-3 subfamily. Therefore this caspase was designated zebrafish caspase-3. Overexpression of zebrafish caspase-3 induced apoptosis and increased ceramide levels in fish fathead minnow tailbud cells and zebrafish embryos. Both ceramide generation and apoptosis induction were inhibited by treatment with a caspase inhibitor, benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone. Moreover, zebrafish caspase-3 mRNA was present in early embryos up to the 1000-cell stage as a maternal factor, and was then expressed throughout the body after the gastrula stage by zygotic expression. These findings indicate that the isolated caspase-3 plays an important role in the induction of ceramide generation as well as apoptosis in fish cells and the zebrafish embryo, and suggest that caspase-3 functions as a modulator of the pro-apoptotic signal in development. C1 Natl Res Inst Fisheries Sci, Yokohama, Kanagawa 2368648, Japan. Tokyo Univ Fisheries, Dept Aquat Biosci, Minato Ku, Tokyo 1088477, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Sakyo Ku, Kyoto 6068507, Japan. RP Yamashita, M (reprint author), Natl Res Inst Fisheries Sci, 2-12-4 Fukuura, Yokohama, Kanagawa 2368648, Japan. NR 53 TC 95 Z9 102 U1 2 U2 18 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 2001 VL 360 BP 39 EP 47 DI 10.1042/0264-6021:3600039 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497QL UT WOS:000172466900005 PM 11695990 ER PT J AU Konradi, C Heckers, S AF Konradi, C Heckers, S TI Antipsychotic drugs and neuroplasticity: Insights into the treatment and neurobiology of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Review DE haloperidol; clozapine; neuroplasticity; gene expression; schizophrenia ID CHRONIC HALOPERIDOL TREATMENT; MEDIAL PREFRONTAL CORTEX; CHRONIC NEUROLEPTIC TREATMENT; MESSENGER-RNA EXPRESSION; D-2 RECEPTOR ANTAGONISTS; INDUCED ORAL DYSKINESIAS; ELEMENT-BINDING PROTEIN; ADULT HUMAN HIPPOCAMPUS; CAUDATE NUCLEI VOLUMES; C-FOS EXPRESSION AB This paper reviews the evidence that antipsychotic drugs induce neuroplasticity. We outline how the synaptic changes induced by the antipsychotic drug haloperidol may help our understanding of the mechanism of action of antipsychotic drugs in general, and how they may help to elucidate the neurobiology of schizophrenia. Studies have provided compelling evidence that haloperidol induces anatomical and molecular changes in the striatum. Anatomical changes have been documented at the level of regional brain volume, synapse morphology, and synapse number. At the molecular level, haloperidol has been shown to cause phosphorylation of proteins and to induce gene expression. The molecular responses to conventional antipsychotic drugs are predominantly observed in the striatum and nucleus accumbens, whereas atypical antipsychotic drugs have a subtler and more widespread impact. We conclude that the ability of antipsychotic drugs to induce anatomical and molecular changes in the brain may be relevant for their antipsychotic properties. The delayed therapeutic action of antipsychotic drugs, together with their promotion of neuroplasticity suggests that modification of synaptic connections by antipsychotic drugs is important for their mode of action. The concept of schizophrenia as a disorder of synaptic organization will benefit from a better understanding of the synaptic changes induced by antipsychotic drugs. (C) 2001 Society of Biological Psychiatry. C1 McLean Hosp, Lab Neuroplast, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Konradi, C (reprint author), McLean Hosp, Lab Neuroplast, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 FU NIDA NIH HHS [R01 DA007134, DA07134, R01 DA007134-14] NR 167 TC 145 Z9 147 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2001 VL 50 IS 10 BP 729 EP 742 DI 10.1016/S0006-3223(01)01267-7 PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 495RJ UT WOS:000172353900001 PM 11720691 ER PT J AU Fabian, TJ Dew, MA Pollock, BG Reynolds, CF Mulsant, BH Butters, MA Zmuda, MD Linares, AM Trottini, M Kroboth, PD AF Fabian, TJ Dew, MA Pollock, BG Reynolds, CF Mulsant, BH Butters, MA Zmuda, MD Linares, AM Trottini, M Kroboth, PD TI Endogenous concentrations of DHEA and DHEA-S decrease with remission of depression in older adults SO BIOLOGICAL PSYCHIATRY LA English DT Article DE DHEA; DHEA-S; depression; neurosteroids; remission; elderly ID PLASMA DEHYDROEPIANDROSTERONE-SULFATE; MAJOR DEPRESSION; PREGNENOLONE-SULFATE; SALIVARY CORTISOL; ANTAGONIST; RECEPTOR; SECRETION; RESPONSES; GABA; AGE AB Background: Clinical studies of endogenous concentrations of dehydroepiandrosterone (DHEA) and its sulfated conjugate DHEA-S in depression are limited. This study was designed to evaluate the influence of successful pharmacological treatment of late-life depression on concentrations of DHEA, DHEA-S and cortisol. Methods: We determined endogenous concentrations of DHEA, DHEA-S and cortisol in elderly control subjects (n = 16) and in elderly depressed patients who remitted (n = 44) or failed to remit (n = 16) with pharmacological treatment. Depressed patients were treated for 12 weeks with either nortriptyline or paroxetine. Results: In remitters, DHEA and DHEA-S concentrations were lower at week 12 than at week 0 (p = .002 and p = .0001, respectively). In the nonremitters and control subjects, neither DHEA nor DHEA-S concentrations changed. Decreases in hormone concentrations were associated with improvement in mood and functioning in depressed patients. Although cortisol concentrations decreased in remitters and nonremitters, the change was not significant. Conclusions: Our delta suggest that the decrease in DHEA and DHEA-S in remitters is related to remission of depression rather than to a direct drug effect on steroids, as nonremitters had no change in hormone concentrations. Biol Psychiatry (C) 2001 Society of Biological. C1 Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Syst, GRECC, Pittsburgh, PA USA. Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. RP Kroboth, PD (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 903 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. RI Trottini, Mario/I-3832-2015 FU NIA NIH HHS [AG05133]; NIMH NIH HHS [MH55756, MH00295, MH01509, MH01613, MH19986, MH37869, MH52247] NR 49 TC 54 Z9 55 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2001 VL 50 IS 10 BP 767 EP 774 DI 10.1016/S0006-3223(01)01198-2 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 495RJ UT WOS:000172353900005 PM 11720695 ER PT J AU Lavori, PW Rush, AJ Wisniewski, SR Alpert, J Fava, M Kupfer, DJ Nierenberg, A Quitkin, FM Sackeim, HA Thase, ME Trivedi, M AF Lavori, PW Rush, AJ Wisniewski, SR Alpert, J Fava, M Kupfer, DJ Nierenberg, A Quitkin, FM Sackeim, HA Thase, ME Trivedi, M TI Strengthening clinical effectiveness trials: Equipoise-stratified randomization SO BIOLOGICAL PSYCHIATRY LA English DT Article DE equipoise; clinical trials; design; methodology; treatment; statistics AB As psychiatric practice patterns evolve to take advantage of the growing list of treatments with proven efficacy, research studies with broader aims will become increasingly-important. Randomized trials may need to accommodate multiple treatment options. In completely randomized designs, patients are assigned at random to one of the options, requiring that patients and clinicians find each of the options acceptable. In "clinician's choice" designs, patients are randomized to a small number of broad strategies and the choice of specific option within the broad strategy is left up to the clinician. The clinician's choice design permits some scope to patient and clinician preferences, but sacrifices the ability to make randomization-based comparisons of specific options. We describe a new approach, which we call the "equipoise stratified" design, that merges the advantages and avoids the disadvantages of the other two designs for clinical trials. The three designs are contrasted, using the National Institute of Mental Health Sequenced Treatment Alternatives to Relieve Depression trial as an example. (C) 2001 Society of Biological Psychiatry. C1 Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. Palo Alto VA, Dept Vet Affairs, Cooperat Studies Program, Palo Alto, CA USA. Univ Texas, SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75235 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. UPMC, Western Psychiat Inst & Clin, Dept Psychiat, New York, NY USA. Columbia Univ, New York State Psychiat Inst, New York, NY USA. RP Lavori, PW (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, M-C 5405, Stanford, CA 94305 USA. OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [MH-30915, N01-MH-90003] NR 7 TC 100 Z9 100 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2001 VL 50 IS 10 BP 792 EP 801 DI 10.1016/S0006-3223(01)01223-9 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 495RJ UT WOS:000172353900008 PM 11720698 ER PT J AU Li, YL Okuno, Y Zhang, P Radomska, HS Chen, HM Iwasaki, H Akashi, K Klemsz, MJ McKercher, SR Maki, RA Tenen, DG AF Li, YL Okuno, Y Zhang, P Radomska, HS Chen, HM Iwasaki, H Akashi, K Klemsz, MJ McKercher, SR Maki, RA Tenen, DG TI Regulation of the PU.1 gene by distal elements SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR PU.1; LOCUS-CONTROL REGION; STIMULATING FACTOR-RECEPTOR; BETA-GLOBIN GENE; LUCIFERASE REPORTER GENE; HIGH-LEVEL EXPRESSION; TRANSGENIC MICE; C/EBP-ALPHA; MYELOID CELLS; DNA-BINDING AB The transcription factor PU.1 (also known as Spi-1) plays a critical role in the development of the myeloid lineages, and myeloid cells derived from PU.1(-/-) animals are blocked at the earliest stage of myeloid differentiation. Expression of the PU.1 gene is tightly regulated during normal hematopoietic development, and dysregulation of PU.1 expression can lead to erythroleukemia. However, relatively little is known about how the PU.1 gene is regulated in vivo. Here it is shown that myeloid cell type-specific expression of PU.1 in stable cell lines and transgenic animals is conferred by a 91-kilobase(kb) murine genomic DNA fragment that consists of the entire PU.1 gene (20 kb) plus approximately 35 kb of upstream and downstream sequences, respectively. To further map the important transcriptional regulatory elements, deoxyribonuclease I hypersensitive site mapping studies revealed at least 3 clusters in the PU.1 gene. A 3.5-kb fragment containing one of these deoxyribonuclease I hypersensitive sites, located -14 kb 5' of the transcriptional start site, conferred myeloid cell type-specific expression in stably transfected cell lines, suggesting that within this region is an element important for myeloid specific expression of PU.1. Further analysis of this myeloid-specific regulatory element will provide insight into the regulation of this key transcriptional regulator and may be useful as a too[ for targeting expression to the myeloid lineage. (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Inst Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. Burnham Inst, La Jolla, CA 92037 USA. RP Tenen, DG (reprint author), Harvard Univ, Inst Med, Rm 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NCI NIH HHS [CA41456]; NIAID NIH HHS [AI30656] NR 52 TC 57 Z9 57 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2001 VL 98 IS 10 BP 2958 EP 2965 DI 10.1182/blood.V98.10.2958 PG 8 WC Hematology SC Hematology GA 492PW UT WOS:000172177600013 PM 11698277 ER PT J AU Shcherbina, A Miki, H Kenney, DM Rosen, FS Takenawa, T Remold-O'Donnell, E AF Shcherbina, A Miki, H Kenney, DM Rosen, FS Takenawa, T Remold-O'Donnell, E TI WASP and N-WASP in human platelets differ in sensitivity to protease calpain SO BLOOD LA English DT Article ID WISKOTT-ALDRICH-SYNDROME; ACTIN-DEPOLYMERIZING PROTEIN; ARP2/3 COMPLEX; ACTIVATION; CDC42; NUCLEATION; EXPRESSION; POLYMERIZATION; INDUCTION; MOTILITY AB Mutations of Wiskoft-Aldrich syndrome protein (WASP) underlie the severe thrombocytopenia and immunodeficiency of the Wiskott-Aldrich syndrome. WASP, a specific blood cell protein, and its close homologue, the broadly distributed N-WASP, function in dynamic actin polymerization processes. Here it is demonstrated that N-WASP is expressed along with WASP, albeit at low levels, in human blood cells. The presence of approximately 160 nmol/L rapidly acting N-WASP molecules may explain the normal capacity of WASP-negative patient platelets for early agonist-induced aggregation and filopodia formation. Ex vivo experiments revealed a significant difference between WASP and N-WASP in sensitivity to calpain, the Ca++-dependent protease activated in agonist-stimulated platelets. Through the use of a series of calpain-containing broken cell systems, it is shown that WASP is cleaved in a Ca++-dependent reaction inhibitable by calpeptin and E64d and that N-WASP is not cleaved, suggesting that the cleavage of WASP by calpain functions in normal platelets as part of a Ca++-dependent switch mechanism that terminates the surface projection phase of blood cell activation processes. (C) 2001 by The American Society of Hematology. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Res Inst Pediat Hematol, Moscow, Russia. Univ Tokyo, Inst Med Sci, Tokyo, Japan. RP Remold-O'Donnell, E (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL059561, HL59561]; NIAID NIH HHS [AI39574, R01 AI039574] NR 31 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2001 VL 98 IS 10 BP 2988 EP 2991 DI 10.1182/blood.V98.10.2988 PG 4 WC Hematology SC Hematology GA 492PW UT WOS:000172177600017 PM 11698281 ER PT J AU Harig, S Witzens, M Krackhardt, AM Trojan, A Barrett, P Broderick, R Zauls, AJ Gribben, JG AF Harig, S Witzens, M Krackhardt, AM Trojan, A Barrett, P Broderick, R Zauls, AJ Gribben, JG TI Induction of cytotoxic T-cell responses against immunoglobulin V region-derived peptides modified at human leukocyte antigen-A2 binding residues SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODY THERAPY; CYTOLYTIC LYMPHOCYTES-T; CLASS-I MOLECULES; MULTIPLE-MYELOMA; PROTECTIVE IMMUNITY; IDIOTYPIC PROTEIN; DENDRITIC CELLS; MELANOMA; IMMUNOGENICITY AB Cytotoxic T-lymphocyte (CTL) responses can be generated against peptides derived from the immunoglobulin (Ig) V region in some but not all patients. The main reason for this appears to be the low peptide-binding affinity of Ig-derived peptides to major histocompatibility complex (MHC) class I molecules and their resulting low immunogenicity. This might be improved by conservative amino acid modifications at the MHC-binding residues of the peptides (heteroclitic peptides). In this study, it was found that in 18 Ig-derived peptides, that heteroclitic peptides from the Ig gene with improved binding to human leukocyte antigen (HLA)-A*0201 can be used to improve CTL responses. Amino acid substitution substantially increased predicted binding affinity, and there was a strong correlation between predicted and actual binding to HLA-A*0201. CTLs generated against the heteroclitic peptide had not only enhanced cytotoxicity against the heteroclitic peptide but also increased killing of antigen-p resenting cells pulsed with the native peptide. Surprisingly, no difference was observed in the frequency of T cells detected by MHC class I peptide tetramers after stimulation with the heteroclitic peptide compared with the native peptide. CTLs generated against heteroclitic peptides could kill patients' tumor cells, showing that Ig-derived peptides can be presented by the tumor cell and that the failure to mount an immune response (among other reasons) likely results from the low immunogenicity of the native Ig-derived peptide. These results suggest that heteroclitic Ig-derived peptides can enhance immunogenicity, thereby eliciting immune responses, and that they might be useful tools for enhancing immunotherapy approaches to treating B-cell malignant diseases. (C) 2001 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. RP Gribben, JG (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA78378, CA81534] NR 46 TC 54 Z9 55 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2001 VL 98 IS 10 BP 2999 EP 3005 DI 10.1182/blood.V98.10.2999 PG 7 WC Hematology SC Hematology GA 492PW UT WOS:000172177600019 PM 11698283 ER PT J AU Holschneider, DP Chen, K Seif, I Shih, JC AF Holschneider, DP Chen, K Seif, I Shih, JC TI Biochemical, behavioral, physiologic, and neurodevelopmental changes in mice deficient in monoamine oxidase A or B SO BRAIN RESEARCH BULLETIN LA English DT Article DE monoamine oxidase; serotonin; norepinephrine; phenylethylamine; dopamine ID ALZHEIMER-TYPE DEMENTIA; FORCED SWIMMING TEST; AGGRESSIVE-BEHAVIOR; D-FENFLURAMINE; RAT-BRAIN; SOMATOSENSORY CORTEX; SEROTONERGIC SYSTEM; TRANSGENIC MICE; NORRIE DISEASE; MEMORY STORAGE AB The availability of mutant mice that lack either MAO A or MAO B has created unique profiles in the central and peripheral availability of serotonin, norepinephrine, dopamine, and phenylethylamine. This paper summarizes some of the current known phenotypic findings in MAO A knock-out mice and contrast these with those of MAO B knock-out mice. Differences are discussed in relation to the biochemical, behavioral, and physiologic changes investigated to date, as well as the role played by redundancy mechanisms, adaptational responses, and alterations in neurodevelopment. (C) 2001 Elsevier Science Inc. C1 Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90089 USA. Univ So Calif, Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90033 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Inst Curie, CNRS, Unite Mixte Rech 146, F-91405 Orsay, France. Univ So Calif, Sch Med, Dept Cell & Neurobiol, Los Angeles, CA USA. RP Shih, JC (reprint author), Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, 1985 Zonal Ave,Rm 528, Los Angeles, CA 90089 USA. FU NIMH NIH HHS [KO5 MH 00796, R01 MH 37020, R01 MH NS62148, R37 MH039085, R37 MH39085]; NINDS NIH HHS [K23 NS062148] NR 89 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 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV 15 PY 2001 VL 56 IS 5 BP 453 EP 462 DI 10.1016/S0361-9230(01)00613-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA 505TE UT WOS:000172931000005 PM 11750790 ER PT J AU Gradishar, WJ Stephenson, P Glover, DJ Neuberg, DS Moore, MR Windschitl, HE Piel, I Abeloff, MD AF Gradishar, WJ Stephenson, P Glover, DJ Neuberg, DS Moore, MR Windschitl, HE Piel, I Abeloff, MD TI A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma - An Eastern Cooperative Oncology Group Study (E8188) SO CANCER LA English DT Article DE breast neoplasm; amifostine; cisplatin; chemoprotection; neurotoxicity; ototoxicity; nephrotoxicity ID CIS-PLATINUM; CANCER; CHEMOTHERAPY; CIS-DICHLORODIAMMINEPLATINUM(II); CYCLOPHOSPHAMIDE; PROTECTION; TISSUES; THERAPY AB BACKGROUND. Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m(2) of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS. A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m(2) intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m(2) was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS. Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS. The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial. (C) 2001 American Cancer Society. C1 Northwestern Univ, Sch Med, Div Hematol & Med Oncol, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Presbyterian Med Ctr, Philadelphia, PA 19104 USA. Grady Mem Hosp, Atlanta, GA 30335 USA. St Cloud Clin, St Cloud, MN USA. Illinois Masonic Med Ctr, Chicago, IL 60657 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. RP Gradishar, WJ (reprint author), Northwestern Univ, Sch Med, Div Hematol & Med Oncol, 676 N St Clair St,Suite 850, Chicago, IL 60611 USA. FU NCI NIH HHS [CA-21115, CA-17145, CA-23318, CA-16116] NR 34 TC 12 Z9 12 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2001 VL 92 IS 10 BP 2517 EP 2522 DI 10.1002/1097-0142(20011115)92:10<2517::AID-CNCR1602>3.0.CO;2-Z PG 6 WC Oncology SC Oncology GA 488ZG UT WOS:000171966700004 PM 11745184 ER PT J AU Lee, SB Kim, SH Bell, DW Wahrer, DCR Schiripo, TA Jorczak, MM Sgroi, DC Garber, JE Li, FP Nichols, KE Varley, JM Godwin, AK Shannon, KM Harlow, E Haber, DA AF Lee, SB Kim, SH Bell, DW Wahrer, DCR Schiripo, TA Jorczak, MM Sgroi, DC Garber, JE Li, FP Nichols, KE Varley, JM Godwin, AK Shannon, KM Harlow, E Haber, DA TI Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni syndrome SO CANCER RESEARCH LA English DT Article ID DNA-DAMAGE RESPONSE; P53 GENE; PROTEIN-KINASE; CHECKPOINT; CANCER; FAMILIES; ATM AB Li Fraumeni Syndrome (LFS) is a multicancer phenotype, most commonly associated with germ-line mutations in TP53. In a kindred with LFS without an inherited TP53 mutation, we have previously reported a truncating mutation (1100delC) in CHK2, encoding a kinase that phosphorylates p53 on Ser(20). Here, we describe a CHK2 missense mutation (R145W) in another LFS family. This mutation destabilizes the encoded protein, reducing its half-life from > 120 min to 30 min. This effect is abrogated by treatment of cells with a proteosome inhibitor, suggesting that CHK2(R145W) is targeted through this degradation pathway. Both 1100delC and R145W germ-line mutations in CHK2 are associated with loss of the wild-type allele in the corresponding tumor specimens, and neither tumor harbors a somatic TP53 mutation. Our observations support the functional significance of CHK2 mutations in rare cases of LFS and suggest that such mutations may substitute for inactivation of TP53. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Mol Pathol Unit, Charlestown, MA 02129 USA. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Childrens Hosp Philadelphia, Div Pediat Oncol, Philadelphia, PA 19104 USA. Canc Res Campaign, Dept Canc Genet, Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England. Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA 74498, CA 84066] NR 26 TC 103 Z9 107 U1 0 U2 4 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 NOV 15 PY 2001 VL 61 IS 22 BP 8062 EP 8067 PG 6 WC Oncology SC Oncology GA 495AF UT WOS:000172317500003 PM 11719428 ER PT J AU Carreira, CM Nasser, SM di Tomaso, E Padera, TP Boucher, Y Tomarev, SI Jain, RK AF Carreira, CM Nasser, SM di Tomaso, E Padera, TP Boucher, Y Tomarev, SI Jain, RK TI LYVE-1 is not restricted to the lymph vessels: Expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis SO CANCER RESEARCH LA English DT Article ID NITRIC-OXIDE; HYALURONAN; RECEPTOR; CELLS; CD44 AB Lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 is thought to be restricted to lymph vessels and has been used as such to show that tumor lymphangiogenesis occurs on overexpression of lymphangiogenic factors in mouse tumor models. However, these studies have not yet been corroborated in human tumors. Here we show, first, that LYVE-1 is not exclusive to the lymph vessels. Indeed, LYVE-1 is also present in normal hepatic blood sinusoidal endothelial cells in mice and humans. Surprisingly, LYVE-1 is absent from the angiogenic blood vessels of human liver tumors and only weakly present in the microcirculation of regenerative hepatic nodules in cirrhosis, though both vessels are largely derived from the liver sinusoids. Second, we propose a novel approach to identify lymphatics in human and murine liver. By combining LYVE-1 and Prox 1 (a transcription factor) immunohistochemistry, we demonstrate that lymphatics are abundant in cirrhosis. In contrast, in human hepatocellular carcinoma and liver metastases, they are restricted to the tumor margin and surrounding liver. The absence of intratumor lymphatics in hepatocellular carcinomas and liver metastases may impair molecular and cellular transport in these tumors. Finally, the presence of LYVE-1 in liver sinusoidal endothelia suggests that LYVE-1 has functions beyond the lymph vascular system. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Stetle Lab Tumor Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Maine Med Ctr Res Inst, Ctr Mol Med, Scarborough, ME 04074 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Stetle Lab Tumor Biol, 100 Blossom St, Boston, MA 02114 USA. NR 28 TC 157 Z9 166 U1 1 U2 2 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 NOV 15 PY 2001 VL 61 IS 22 BP 8079 EP 8084 PG 6 WC Oncology SC Oncology GA 495AF UT WOS:000172317500006 ER PT J AU Rubin, BP Singer, S Tsao, C Duensing, A Lux, ML Ruiz, R Hibbard, MK Chen, CJ Xiao, S Tuveson, DA Demetri, GD Fletcher, CDM Fletcher, JA AF Rubin, BP Singer, S Tsao, C Duensing, A Lux, ML Ruiz, R Hibbard, MK Chen, CJ Xiao, S Tuveson, DA Demetri, GD Fletcher, CDM Fletcher, JA TI KIT activation is a ubiquitous feature of gastrointestinal stromal tumors SO CANCER RESEARCH LA English DT Article ID LIGAND-INDEPENDENT ACTIVATION; RECEPTOR TYROSINE KINASE; PROTOONCOGENE C-KIT; INTERSTITIAL-CELLS; CONSTITUTIVE ACTIVATION; MALIGNANT-MELANOMA; POINT MUTATION; CAJAL; DOMAIN; GENE AB Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, and they are generally resistant to chemotherapy and radiation therapy. Most GISTs express the KIT receptor tyrosine kinase protein, and a subset of GISTs contain activating mutations within the KIT juxtamembrane region. We evaluated 48 GISTs, including 10 benign, 10 borderline, and 28 malignant cases, to determine whether KIT expression and activation are general properties of these tumors. Immunohistochemical KIT expression was demonstrated in each case. Somatic KIT mutations were found in 44 tumors (92%), of which 34 (71%) had juxtamembrane region mutations. Other GISTs had KIT mutations in the extracellular region (n = 6) and in two different regions in the tyrosine kinase domain (n = 4). Contrary to previous reports, KIT mutations were not identified preferentially in higher-grade tumors: indeed, they were found in each of 10 histologically benign GISTs. Notably, mutations in all KIT domains were associated with high-level KIT activation/phosphorylation, and KIT activation was also demonstrated in the four GISTs that lacked detectable KIT genomic and cDNA mutations. These studies underscore the role of KIT activation in GIST pathogenesis, and they suggest that activated KIT might represent a universal therapeutic target in GISTs. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. OI Duensing, Anette/0000-0002-0168-4067 NR 33 TC 661 Z9 693 U1 1 U2 11 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 NOV 15 PY 2001 VL 61 IS 22 BP 8118 EP 8121 PG 4 WC Oncology SC Oncology GA 495AF UT WOS:000172317500014 PM 11719439 ER PT J AU Yang, JM Luan, J Yu, YC Li, CX DePinho, RA Chin, L Richmond, A AF Yang, JM Luan, J Yu, YC Li, CX DePinho, RA Chin, L Richmond, A TI Induction of melanoma in murine macrophage inflammatory protein 2 transgenic mice heterozygous for inhibitor of kinase/alternate reading frame SO CANCER RESEARCH LA English DT Article ID GROWTH-STIMULATORY ACTIVITY; MALIGNANT-MELANOMA; CELLULAR-TRANSFORMATION; NORMAL MELANOCYTES; ALPHA EXPRESSION; SKIN-CANCER; CELLS; MUTATIONS; RAS; OVEREXPRESSION AB The molecular and genetic events that contribute to the genesis and progression of cutaneous malignant melanoma are poorly understood, attributable in large part to the different genetic alterations accompanying tumorigenesis. Inhibitor of kinase 4a (INK4a) is often inactivated in families with hereditary melanoma. Loss of INK4a/alternate reading frame (ARF) in mice is associated with increased incidence of other tumors such as lymphoma and fibrosarcoma. However, the incidence of melanoma in INK4a/ARF-deficient mice is very low. Our previous studies have revealed that the CXC chemokine, CXCL1, is overexpressed in human malignant melanoma cells and is linked to transformation of immortalized murine melanocytes. To study the direct role of CXCL1 on the genesis of primary melanoma lesions, transgenic mouse lines were established that express the murine homologue of CXCL1, murine macrophage inflammatory protein 2 (MIP-2), under the transcriptional control of the tyrosinase promoter/enhancer (Tyr-MIP-2) in the mice that were deficient or not deficient for INK4a/ARF. Strong MIP-2 immunoreactivity was associated with pigmented melanocytes in the hyperproliferative hair follicles in the Tyr-MIP-2 transgenic mice, and the level of MIP-2 expression was similar in both INK4a/ARF heterozygous or wild-type mice. After treatment of mice with 7,12-dimethylbenz(a)anthracene, cutaneous melanomas formed in 12% (17/145) of the Tyr-MIP-2 transgene-positive mice, whereas only 2% (3/146) of the Tyr-MIP-2 transgene-negative mice developed melanoma. When melanocytes cultured from MIP-2 transgenic mice null for INK4a/ARF were transplanted into nude mice, melanoma formation occurred in 83% (10/12) of the cases with a latency period of 3 months. However, no melanoma lesions arose in nude mice injected with INK4a/ARF -/- melanocytes, which did not express the MIP-2 transgene. Our results demonstrate that constitutive expression of MIP-2 in INK4a/ARF-deficient melanocytes facilitates formation of malignant melanoma. C1 Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA. Vet Affairs Med Ctr, Nashville, TN 37232 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. RP Richmond, A (reprint author), Vanderbilt Univ, Sch Med, Dept Canc Biol, 221 Kirkland Hall, Nashville, TN 37232 USA. RI Richmond, Ann/A-3048-2014 FU NCI NIH HHS [R01 CA056704, R01 CA056704-07, R01 CA056704-09, CA56704, R01 CA056704-08]; NIAMS NIH HHS [5P30 AR41943] NR 43 TC 27 Z9 28 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 NOV 15 PY 2001 VL 61 IS 22 BP 8150 EP 8157 PG 8 WC Oncology SC Oncology GA 495AF UT WOS:000172317500019 PM 11719444 ER PT J AU Ross, AJ Amy, SP Mahar, PL Lindsten, T Knudson, CM Thompson, CB Korsmeyer, SJ MacGregor, GR AF Ross, AJ Amy, SP Mahar, PL Lindsten, T Knudson, CM Thompson, CB Korsmeyer, SJ MacGregor, GR TI BCLW mediates survival of postmitotic Sertoli cells by regulating BAX activity SO DEVELOPMENTAL BIOLOGY LA English DT Article DE BCLW; BAX; BAK; c-kit; testis; Sertoli cell; apoptosis; mouse ID FAMILY MEMBERS; DEFICIENT MICE; GERM-CELLS; BH3 DOMAIN; TESTICULAR DEVELOPMENT; MESSENGER-RNA; APOPTOSIS; DEATH; TESTIS; RAT AB Male mice deficient in BCLW, a death-protecting member of the BCL2 family, are sterile due to an arrest in spermatogenesis that is associated with a gradual loss of germ cells and Sertoli cells from the testis. As Bclw is expressed in both Sertoli cells and diploid male germ cells, it has been unclear which of these cell types requires BCLW in a cell-autonomous manner for survival. To determine whether death of Sertoli cells in Bclw mutants is influenced by the protracted loss of germ cells, we examined testes from Bclw/c-kit double mutant mice, which lack germ cells from birth. Loss of BCLW-deficient Sertoli cells occurs in the absence of germ cells, indicating that germ cell death is not required to mediate loss of Sertoli cells in BCLW-deficient mice. This suggests that Sertoli cells require BCLW in a cell-intrinsic manner for long-term survival. The loss of Sertoli cells in Bclw mutants commences shortly after Sertoli cells have become postmitotic. In situ hybridization analysis indicates that Bclw is expressed in Sertoli cells both before and after exit from mitosis. Therefore, Bclw-independent pathways promote the survival of undifferentiated, mitotic Sertoli cells. We show that BAX and BAK, two closely related death-promoting members of the BCL2 family, are expressed in Sertoli cells. To determine whether either BAX or BAK activity is required for Sertoli cell death in Bclw mutant animals, we analyzed survival of Sertoli cells in Bclw/Bax and Bclw/Bak double homozygous mutant mice. While mutation of Bak had no effect, ablation of Bax suppressed the loss of Sertoli cells in Bclw mutants. Thus, BCLW mediates survival of postmitotic Sertoli cells in the mouse by suppressing death-promoting activity of BAX. (C) 2001 Academic Press. C1 Emory Univ, Sch Med, Ctr Mol Med, Atlanta, GA 30322 USA. Emory Univ, Grad Program Biochem Cell & Dev Biol, Atlanta, GA 30322 USA. Univ Penn, Abramson Family Canc Res Inst, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Dept Lab Med, Philadelphia, PA 19104 USA. Univ Iowa, Coll Med, Dept Pathol, Iowa City, IA 52242 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Med, Boston, MA 02115 USA. RP MacGregor, GR (reprint author), Emory Univ, Sch Med, Ctr Mol Med, Atlanta, GA 30322 USA. NR 57 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 2001 VL 239 IS 2 BP 295 EP 308 DI 10.1006/dbio.2001.0445 PG 14 WC Developmental Biology SC Developmental Biology GA 497KB UT WOS:000172453300010 PM 11784036 ER PT J AU Caroppo, R Gerbino, A Debellis, L Kifor, O Soybel, DI Brown, EM Hofer, AM Curci, S AF Caroppo, R Gerbino, A Debellis, L Kifor, O Soybel, DI Brown, EM Hofer, AM Curci, S TI Asymmetrical, agonist-induced fluctuations in local extracellular [Ca2+] in intact polarized epithelia SO EMBO JOURNAL LA English DT Article DE extracellular calcium microdomains; extracellular calcium-sensing receptor; intercellular signaling; PMCA; store-operated calcium channels ID CALCIUM-SENSING RECEPTOR; PLASMA-MEMBRANE CA2+-ATPASE; PANCREATIC ACINAR-CELLS; FROG GASTRIC-MUCOSA; INTRACELLULAR CALCIUM; BASOLATERAL MEMBRANE; PARIETAL-CELLS; OXYNTIC CELLS; CA2+-SENSING RECEPTOR; (CA-O(2+))-SENSING RECEPTOR AB We recently proposed that extracellular Ca2+ ions participate in a novel form of intercellular communication involving the extracellular Ca2+-sensing receptor (CaR). Here, using Ca2+-selective microelectrodes, we directly measured the profile of agonist-induced [Ca2+](ext) changes in restricted domains near the basolateral or luminal membranes of polarized gastric acid-secreting cells. The Ca2+-mobilizing agonist carbachol elicited a transient, La3+-sensitive decrease in basolateral [Ca2+] (average approximate to 250 muM, but as large as 530 muM). Conversely, carbachol evoked an HgCl2-sensitive increase in [Ca2+] (average approximate to 400 muM, but as large as 520 muM) in the lumen of single gastric glands. Both responses were significantly reduced by pretreatment with sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pump inhibitors or with the intracellular Ca2+ chelator BAPTA-AM. Immunofluorescence experiments demonstrated an asymmetric localization of plasma membrane Ca2+ ATPase (PMCA), which appeared to be partially co-localized with Calk and the gastric H+/K+-ATPase in the apical membrane of the acid-secreting cells. Our data indicate that agonist stimulation results in local fluctuations in [Ca2+](ext) that would be sufficient to modulate the activity of the CaR on neighboring cells. C1 Univ Bari, Dipartimento Fisiol Gen & Ambientale, I-70126 Bari, Italy. Brigham & Womens Hosp, Dept Med, Membrane Biol Program, Div Endocrine Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA. RP Curci, S (reprint author), Univ Bari, Dipartimento Fisiol Gen & Ambientale, Via Amendola 165A, I-70126 Bari, Italy. OI Debellis, Lucantonio/0000-0002-7571-0969; CAROPPO, Rosa/0000-0002-8773-8985; Gerbino, Andrea/0000-0002-2839-0130 FU NIDDK NIH HHS [R01 DK052005, DK 4145, DK 48330, DK 52005, DK34854, DK44571, P30 DK034854] NR 74 TC 40 Z9 44 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 15 PY 2001 VL 20 IS 22 BP 6316 EP 6326 DI 10.1093/emboj/20.22.6316 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 496NN UT WOS:000172403000015 PM 11707403 ER PT J AU Yamada, A Chandraker, A Laufer, TM Gerth, AJ Sayegh, MH Auchincloss, H AF Yamada, A Chandraker, A Laufer, TM Gerth, AJ Sayegh, MH Auchincloss, H TI Cutting edge: Recipient MHC class II expression is required to achieve long-term survival of murine cardiac allografts after costimulatory blockade SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSPLANTATION TOLERANCE; INDIRECT RECOGNITION; T-CELLS; INFECTIOUS TOLERANCE; LINKED SUPPRESSION; THYMIC RECOGNITION; RENAL-ALLOGRAFTS; GRAFT-REJECTION; DEFICIENT MICE; IN-VIVO AB To study the role of the direct and indirect pathways in achieving tolerance, we used genetically altered mouse strains in two ways: 1) MHC class II-deficient mice were used as donors of skin and cardiac grafts to eliminate the direct CD4(+) T cell response, and 2) B6 II(-)4(+) mice, which are MHC class II-deficient mice expressing an MHC class II transgene only on thymic epithelium, were used as recipients of normal grafts. These mice cannot mount an indirect response. Eliminating the indirect pathway actually made it more difficult to achieve prolonged allograft survival when we used costimulatory blockade than when both pathways were available. Costimulatory blockade was ineffective even when CD4(+) T cells from normal animals were transferred into recipients that lacked MHC class II molecules. These results suggest that an active CD4(+) response through the indirect pathway is necessary for costimulatory blockade to be effective in prolonging allograft survival. C1 Massachusetts Gen Hosp, Transplantat Unit, Surg Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Lab Immunogenet & Transplantat, Div Renal, Boston, MA 02115 USA. Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Surg Serv, WAC478,15 Parkman St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI-38397, AI-34965] NR 30 TC 93 Z9 97 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2001 VL 167 IS 10 BP 5522 EP 5526 PG 5 WC Immunology SC Immunology GA 491JZ UT WOS:000172106400002 PM 11698419 ER PT J AU Exley, MA Tahir, SMA Cheng, O Shaulov, A Joyce, R Avigan, D Sackstein, R Balk, SP AF Exley, MA Tahir, SMA Cheng, O Shaulov, A Joyce, R Avigan, D Sackstein, R Balk, SP TI Cutting edge: A major fraction of human bone marrow lymphocytes are Th2-like CD1d-reactive T cells that can suppress mixed lymphocyte responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VERSUS-HOST DISEASE; NKT CELLS; RECOGNITION; ACTIVATION; CD1; TRANSPLANTATION; TOLERANCE; SUBSETS; NKR-P1A; SYSTEM AB Murine bone marrow (BM) NK T cells can suppress graft-vs-host disease, transplant rejection, and MLRs. Human BM contains T cells with similar potential. Human BM was enriched for NK T cells, similar to 50% of which recognized the nonpolymorphic CD1d molecule. In contrast to the well-characterized blood-derived CD1d-reactive invariant NK T cells, the majority of human BM CD1d-reactive T cells used diverse TCR. Healthy donor invariant NK T cells rapidly produce large amounts of IL-4 and IFN-gamma and can influence Th1/Th2 decision-making. Healthy donor BM CD1d-reactive T cells were Th2-biased and suppressed NMR and, unlike the former, responded preferentially to CD1d(+) lymphoid cells. These results identify a novel population of human T cells which may contribute to B cell development and/or maintain Th2 bias against autoimmune T cell responses against new B cell Ag receptors. Distinct CD1d-reactive T cell populations have the potential to suppress graft-vs-host disease and stimulate antitumor responses. C1 Beth Israel Deaconess Med Ctr, Canc Biol Program, Boston, MA 02215 USA. Harvard Univ, Sch Med, Bone Marrow Transplant Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Program, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Exley, MA (reprint author), Beth Israel Deaconess Med Ctr, Canc Biol Program, HIM 1047,330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [CA84156, CA89567]; NIAID NIH HHS [AI42955] NR 36 TC 103 Z9 105 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2001 VL 167 IS 10 BP 5531 EP 5534 PG 4 WC Immunology SC Immunology GA 491JZ UT WOS:000172106400004 PM 11698421 ER PT J AU Russell, PS Chase, CM Sykes, M Ito, H Shaffer, J Colvin, RB AF Russell, PS Chase, CM Sykes, M Ito, H Shaffer, J Colvin, RB TI Tolerance, mixed chimerism, and chronic transplant arteriopathy SO JOURNAL OF IMMUNOLOGY LA English DT Article; Proceedings Paper CT 1st Joint Meeting of the American-Society-of-Transplantation/American-Society-of-Transplant-Surge ons CY MAY 13-17, 2000 CL CHICAGO, ILLINOIS SP Amer Soc Transplantat, Amer Transplant Surgeons ID BONE-MARROW TRANSPLANTATION; NATURAL-KILLER CELLS; CORONARY ATHEROSCLEROSIS; MONOCLONAL-ANTIBODY; CHRONIC REJECTION; MOUSE HEARTS; HEMATOPOIETIC CHIMERISM; CARDIAC ALLOGRAFTS; THYMIC IRRADIATION; INTERFERON-GAMMA AB Much evidence supports the conclusion that immunological responses to donor-specific incompatibilities are a major factor in producing "chronic" transplant rejection, including the arteriopathy (atherosclerosis) commonly present. Our experiments explored the effects of altered immunological responsiveness to these Ags on the formation of arteriopathy in transplanted mouse hearts. Specific immunological nonreactivity, or tolerance, was induced either by neonatal administration of allogeneic spleen cells (from F-1 donors between class 1-mismatched donor and recipient strains), resulting in "classical" immunological tolerance, or by bone marrow infusion to suitably prepared adult recipients, either fully MHC mismatched or class I mismatched, yielding "mixed chimerism." Both approaches obviated systemic graft-versus-host effects. In both groups, donor-specific skin grafts survived perfectly and donor cell chimerism persisted. Specific Abs were undetectable in all recipients. Most transplants to either group of tolerant recipients developed striking vasculopathy in their coronary arteries (12 of 15 in neonatal tolerance and 15 of 23 in mixed chimeras). Neointimal infiltrates included CD4 and CD8 T cells and macrophages. Only 2 of 29 contemporary isotransplants showed any evidence of vasculopathy. Recipients essentially incapable of T and B cell responses (C.B-17/SCED and RAG1(-/-)) were also used. Transplants into these animals developed vasculopathy in 16 of 31 instances. Accordingly, in this setting, vasculopathy develops in the presence of H-2 gene-determined incompatibility even with minimal conventional immune reactivity. Perhaps innate responsiveness, that could include NK cell activity, can create such arteriopathic lesions. More evidence is being sought regarding this process. C1 Harvard Univ, Dept Surg, Transplantat Unit, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Russell, PS (reprint author), Harvard Univ, Dept Surg, Transplantat Unit, Massachusetts Gen Hosp,Sch Med, White 510, Boston, MA 02114 USA. FU NHLBI NIH HHS [R0-1 HL43340, R0-1 HL49915] NR 51 TC 60 Z9 60 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2001 VL 167 IS 10 BP 5731 EP 5740 PG 10 WC Immunology SC Immunology GA 491JZ UT WOS:000172106400029 PM 11698446 ER PT J AU Muir, WW Woolf, CJ AF Muir, WW Woolf, CJ TI Mechanisms of pain and their therapeutic implications SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID RAT SPINAL-CORD; PRIMARY SENSORY NEURONS; NERVE GROWTH-FACTOR; DORSAL-HORN; SUBSTANTIA-GELATINOSA; POSTOPERATIVE PAIN; PERIPHERAL INFLAMMATION; CENTRAL SENSITIZATION; NEUROBIOLOGICAL BASIS; CAPSAICIN RECEPTOR C1 Ohio State Univ, Coll Vet Med, Dept Vet Clin Sci, Columbus, OH 43210 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. RP Muir, WW (reprint author), Ohio State Univ, Coll Vet Med, Dept Vet Clin Sci, Columbus, OH 43210 USA. NR 92 TC 65 Z9 68 U1 2 U2 10 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD NOV 15 PY 2001 VL 219 IS 10 BP 1346 EP 1356 DI 10.2460/javma.2001.219.1346 PG 11 WC Veterinary Sciences SC Veterinary Sciences GA 493DA UT WOS:000172205700016 PM 11724168 ER PT J AU Kyriakis, JM AF Kyriakis, JM TI Signal transduction - Life-or-death decisions SO NATURE LA English DT Editorial Material ID ACTIVATION; STRESS; INDUCTION; GADD45; JNK C1 Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA 02129 USA. RP Kyriakis, JM (reprint author), Massachusetts Gen Hosp, Diabet Res Lab, 149 13th St, Charlestown, MA 02129 USA. NR 13 TC 34 Z9 36 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 15 PY 2001 VL 414 IS 6861 BP 265 EP 266 DI 10.1038/35104735 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 492CM UT WOS:000172150700029 PM 11713514 ER PT J AU Mohr, JP Thompson, JLP Lazar, RM Levin, B Sacco, RL Furie, KL Kistler, JP Albers, GW Pettigrew, LC Adams, HP Jackson, CM Pullicino, P AF Mohr, JP Thompson, JLP Lazar, RM Levin, B Sacco, RL Furie, KL Kistler, JP Albers, GW Pettigrew, LC Adams, HP Jackson, CM Pullicino, P CA Warfarin-Aspirin Recurrent Stroke TI A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONVALVULAR ATRIAL-FIBRILLATION; RANDOMIZED TRIAL; SECONDARY PREVENTION; CEREBRAL INFARCTION; OPTIMAL INTENSITY; RISK-FACTORS; ANTICOAGULATION; THERAPY; SUBTYPES AB Background: Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke. Methods: In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years. Results: The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke. Conclusions: Over a two-year period, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives. C1 Columbia Presbyterian Med Ctr, Inst Neurol, New York, NY 10032 USA. Columbia Presbyterian Med Ctr, Dept Biostat, New York, NY 10032 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Univ Kentucky, Med Ctr, Louisville, KY USA. Univ Iowa Hlth Care, Iowa City, IA USA. Univ Calif San Diego, San Diego, CA 92103 USA. SUNY Buffalo, Buffalo, NY 14260 USA. RP Mohr, JP (reprint author), Columbia Presbyterian Med Ctr, Inst Neurol, 710 W 168th St, New York, NY 10032 USA. FU NINDS NIH HHS [R01-NS-28371] NR 39 TC 580 Z9 599 U1 0 U2 14 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 NOV 15 PY 2001 VL 345 IS 20 BP 1444 EP 1451 DI 10.1056/NEJMoa011258 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 491WH UT WOS:000172132700002 PM 11794192 ER PT J AU Grinspoon, SK Kronenberg, HM Gonzalez, RG Schmitt, WP Hedley-Whyte, ET AF Grinspoon, SK Kronenberg, HM Gonzalez, RG Schmitt, WP Hedley-Whyte, ET TI An 81-year-old man with hypothermia, bradycardia, and confusion. Non small-cell carcinoma of the lung, metastatic to the hypothalamus, pituitary stalk, and pituitary gland. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ADRENAL INSUFFICIENCY; ASSAYS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 NOV 15 PY 2001 VL 345 IS 20 BP 1483 EP 1488 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 491WH UT WOS:000172132700008 ER PT J AU Chen, JQ Kuhlencordt, PJ Astern, J Gyurko, R Huang, PL AF Chen, JQ Kuhlencordt, PJ Astern, J Gyurko, R Huang, PL TI Hypertension does not account for the accelerated atherosclerosis and development of aneurysms in male apolipoprotein E/endothelial nitric oxide synthase double knockout mice SO CIRCULATION LA English DT Article DE arteriosclerosis; nitric oxide synthase; aneurysm; hypertension; hydralazine ID E-DEFICIENT MICE; LACKING; DYSFUNCTION; LESIONS AB Background-Apolipoprotein E (apoE)/endothelial nitric oxide synthase (eNOS) double knockout (DKO) mice demonstrate accelerated atherosclerosis and develop abdominal aortic aneurysms and aortic dissection, suggesting a role for eNOS in suppressing atherogenesis. To test whether accelerated atherosclerosis and aortic aneurysms were due to hypertension, we administered hydralazine to male apoE/eNOS DKO mice to reduce blood pressure. Methods and Results-Male apoE/eNOS DKO mice were treated with hydralazine in their drinking water (250 mg/L) using a dose that lowers the blood pressure to levels seen in apoE KO mice. The mice were fed a Western-type diet for 16 weeks, and lesion formation was assessed by inspection of the vessel and staining with Sudan IV. Hydralazine-treated, normotensive male apoE/eNOS DKO mice developed increased aortic lesion areas (30.0 +/-2.8%, n=11) compared with male apoE KO mice (14.6 +/-0.8%, n=7). The extent of lesion formation was not significantly different from male apoE/eNOS DKO mice that were not given hydralazine (28.3 +/-3.1%, n=9). Four of 11 hydralazine-treated male apoE/eNOS DKO mice developed abdominal aortic aneurysms. Conclusions-Hypertension is not required for the accelerated atherosclerosis seen in apoE/eNOS DKO animals, and control of hypertension during a 16-week period does not prevent aortic aneurysm formation. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 E 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL-52818]; NINDS NIH HHS [NS-33335] NR 15 TC 109 Z9 110 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 NOV 13 PY 2001 VL 104 IS 20 BP 2391 EP 2394 DI 10.1161/hc4501.099729 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 494CF UT WOS:000172260600012 PM 11705813 ER PT J AU Cheng, H Cenciarelli, C Shao, ZP Vidal, M Parks, WP Pagano, M Cheng-Mayer, C AF Cheng, H Cenciarelli, C Shao, ZP Vidal, M Parks, WP Pagano, M Cheng-Mayer, C TI Human T cell leukemia virus type 1 Tax associates with a molecular chaperone complex containing hTid-1 and Hsp70 SO CURRENT BIOLOGY LA English DT Article ID NF-KAPPA-B; DNAJ HOMOLOG; J-DOMAIN; PROTEIN; ACTIVATION; DROSOPHILA; ANTIGEN; BINDING; CREB; GENE AB Tax, an oncogenic viral protein encoded by human T cell leukemia virus type 1 (HTLV-1), induces cellular transformation of T lymphocytes by modulating a variety of cellular gene expressions [1]. Identifying cellular partners that interact with Tax constitutes the first step toward elucidating the molecular basis of Tax-induced transformation. Here, we report a novel Tax-interacting protein, hTid-1. hTid-1, a human homolog of the Drosophila tumor suppressor protein Tid56, was initially characterized based on its interaction with the HPV-16 E7 oncoprotein [2]. hTid-1 and Tid56 are members of the DnaJ family [2, 3], which contains a highly conserved signature J domain that regulates the activities of heat shock protein 70 (Hsp70) by serving as cochaperone [4-6]. In this context, the molecular chaperone complex is involved in cellular signaling pathways linked to apoptosis, protein folding, and membrane translocation and in modulation of the activities of tumor suppressor proteins, including retinoblastoma, p53, and WT1 [7-12]. We find that expression of hTid-1 inhibits the transformation phenotype of two human lung adenocarcinoma cell lines. We show that Tax interacts with hTid-1 via a central cysteine-rich domain of hTid-1 while a signature J domain of hTid-1 mediates its binding to Hsp70 in HEK cells. Importantly, Tax associates with the molecular chaperone complex containing both hTid-1 and Hsp70 and alters the cellular localization of hTid-1 and Hsp70. In the absence of Tax, expression of the hTid-1/Hsp70 molecular complex is targeted to perinuclear mitochondrial clusters. In the presence of Tax, hTid-1 and its associated Hsp70 are sequestered within a cytoplasmic "hot spot" structure, a subcellular distribution that is characteristic of Tax in HEK cells. C1 NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10021 USA. RP Cheng, H (reprint author), NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. NR 24 TC 51 Z9 55 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 13 PY 2001 VL 11 IS 22 BP 1771 EP 1775 DI 10.1016/S0960-9822(01)00540-1 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 495WM UT WOS:000172363400023 PM 11719219 ER PT J AU Palmer, RE Kotsianti, A Cadman, B Boyd, T Gerald, W Haber, DA AF Palmer, RE Kotsianti, A Cadman, B Boyd, T Gerald, W Haber, DA TI WT1 regulates the expression of the major glomerular podocyte membrane protein Podocalyxin SO CURRENT BIOLOGY LA English DT Article ID TUMOR SUPPRESSOR GENE; EPITHELIAL-CELL; DRASH SYNDROME; WILMS; KIDNEY; IDENTIFICATION; MUTATIONS; SEQUENCE; BINDING AB The WT1 tumor suppressor gene encodes a zinc finger transcription factor expressed in differentiating glomerular podocytes. Complete inactivation of WT1 in the mouse leads to failure of mesenchymal induction and renal agenesis, an early developmental phenotype that prevents analysis of subsequent stages in glomerular differentiation [1]. In humans with Denys-Drash Syndrome, a heterozygous germline mutation in WT1 is associated with specific defects in glomeruli and an increased risk for developing Wilms Tumor [2, 3]. WT1 target genes implicated in cell cycle regulation and cellular proliferation have been proposed [4], but the link between WT1 function and glomerular differentiation is unexplained. Here, we show that inducible expression of WT1 in rat embryonic kidney cell precursors leads to the induction of endogenous Podocalyxin, the major structural membrane protein of glomerular podocytes, which is implicated in the maintenance of filtration slits. Binding of WT1 to conserved elements within the Podocalyxin gene promoter results in potent transcriptional activation, and the specific expression pattern of Podocalyxin in the developing kidney mirrors that of WT1 itself. These observations support a role for WT1 in the specific activation of a glomerular differentiation program in renal precursors and provide a molecular basis for the glomerulonephropathy that is characteristic of Denys-Drash Syndrome. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Baystate Med Ctr, Dept Pathol, Springfield, MA 01199 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA 58596, CA 84999] NR 22 TC 97 Z9 101 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 13 PY 2001 VL 11 IS 22 BP 1805 EP 1809 DI 10.1016/S0960-9822(01)00560-7 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 495WM UT WOS:000172363400029 PM 11719225 ER PT J AU Feikin, DR Elie, CM Goetz, MB Lennox, JL Carlone, GM Romero-Steiner, S Holder, PF O'Brien, WA Whitney, CG Butler, JC Breiman, RF AF Feikin, DR Elie, CM Goetz, MB Lennox, JL Carlone, GM Romero-Steiner, S Holder, PF O'Brien, WA Whitney, CG Butler, JC Breiman, RF TI Randomized trial of the quantitative and functional antibody responses to a 7-valent pneumococcal conjugate vaccine and/or 23-valent polysaccharide vaccine among HIV-infected adults SO VACCINE LA English DT Article DE pneumococcal disease; conjugate vaccines; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; STREPTOCOCCUS-PNEUMONIAE; GLYCOPROTEIN CONJUGATE; DISEASE; CHILDREN; ASSAY AB In a double-blinded, randomized trial, human immunodeficiency virus (HIV)-infected adults with greater than or equal to 200 CD4 cells/mul received placebo (PL), 7-valent conjugate. or 23-valent pneumococcal polysaccharide (PS) vaccine in one of the following two-dose combinations given 8 weeks apart: conjugate-conjugate, conjugate-polysaccharide. placebo-polysaccharide, placebo-placebo. A total of 67 persons completed the study. Neither significant increases in HIV viral load nor severe adverse reactions occurred in any group. After controlling for confounders. when compared with persons receiving placebo-polysaccharide, persons receiving conjugate-conjugate and conjugate-polysaccharide had higher antibody concentrations (serotypes 4. 6B, 9V and serotype 23F respectively) and opsonophagocytic titers (functional antibody assay, serotypes 9V, 23F and serotypes 4, 6B, 9V. respectively) after the second dose (P < 0.05). The second dose with either conjugate or polysaccharide following the first conjugate dose, however, produced no further increase in immune responses. Published by Elsevier Science Ltd. C1 CDCP, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Resp Dis Branch, Atlanta, GA 30332 USA. Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Emory Univ, Atlanta, GA 30322 USA. Grady Infect Dis Program, Atlanta, GA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Feikin, DR (reprint author), CDCP, Natl Ctr Infect Dis, Div Bacterial & Mycot Dis, Resp Dis Branch, 1600 Clifton Rd,MS-C23, Atlanta, GA 30332 USA. RI Lennox, Jeffrey/D-1654-2014; OI Lennox, Jeffrey/0000-0002-2064-5565; Romero-Steiner, Sandra/0000-0003-4128-7768; Goetz, Matthew/0000-0003-4542-992X NR 32 TC 96 Z9 101 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 12 PY 2001 VL 20 IS 3-4 BP 545 EP 553 DI 10.1016/S0264-410X(01)00347-4 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 492DP UT WOS:000172153400034 PM 11672921 ER PT J AU Ishikawa, T Yang, H Tache, Y AF Ishikawa, T Yang, H Tache, Y TI Microinjection of bombesin into the ventrolateral reticular formation inhibits peripherally stimulated gastric acid secretion through spinal pathways in rats SO BRAIN RESEARCH LA English DT Article DE bombesin; CRF; gastric secretions; spinal cord; brainstem; sympathetic ID DORSAL MOTOR NUCLEUS; SYMPATHETIC PREGANGLIONIC NEURONS; CORTICOTROPIN-RELEASING FACTOR; CENTRAL-NERVOUS-SYSTEM; VAGAL EFFERENT DISCHARGE; MUCOSAL BLOOD-FLOW; IMMUNOREACTIVE NEURONS; RECEPTOR SUBTYPES; BRAIN; MEDULLA AB Bombesin injected into the cisterna magna potently inhibits gastric acid secretion stimulated by intravenous infusion of pentagastrin. Sites in the medulla oblongata where bombesin acts to suppress gastric acid secretion were investigated in urethane-anesthetized rats with gastric cannula. Bombesin or vehicle was injected into the medullary parenchyma or intracisternally (i.c.) 60 min after the start of an intravenous pentagastrin infusion; gastric acid secretion was monitored every 10 min for 20 min before and 150 min after the start of pentagastrin. Bombesin (0.2, 0.6 or 6.2 pmol) microinjected into the ventrolateral reticular formation (VLRF) inhibited dose-dependently the net acid response to pentagastrin by 40.8 +/- 11.1. 75.4 +/- 12.8 and 96.7 +/- 19.4%, respectively, at the 40-50 min period after microinjection compared with the vehicle group. Bombesin action in the VLRF was long lasting (96% inhibition still observed at 90 min after 6.2 pmol), and completely abolished by cervical spinal cord transection at the C6 level. By contrast, bombesin injected i.c. at 0.2 or 0.6 pmol had no effect while at 6.2 pmol, there was a 79.0 +/- 3.9% peak inhibition of pentagastrin-stimulated acid secretion. Bombesin (6.2 pmol) injected into the dorsal motor nucleus reduced the acid response to pentagastrin by 29%. The parvicellular and gigantocellular reticular nuclei were not responsive to bombesin. These results indicate that bombesin acts in the VLRF to inhibit pentagastrin-stimulated gastric acid secretion through spinal pathways, suggesting a potential role of medullary VLRF area in the sympathetic control of gastric acid secretion. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), Univ Calif Los Angeles, Vet Adm Greater Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-30110, DK 33061] NR 50 TC 2 Z9 2 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 NOV 9 PY 2001 VL 918 IS 1-2 BP 1 EP 9 DI 10.1016/S0006-8993(01)02833-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 494TN UT WOS:000172302100001 PM 11684036 ER PT J AU Kearns, AE Donohue, MM Sanyal, B Demay, MB AF Kearns, AE Donohue, MM Sanyal, B Demay, MB TI Cloning and characterization of a novel protein kinase that impairs osteoblast differentiation in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-2; GROWTH-FACTOR RECEPTOR-2; IN-VITRO; CLEIDOCRANIAL DYSPLASIA; TRANSCRIPTION FACTOR; EXPRESSION; GENE; CELLS; FIBROBLAST; CBFA1 AB The bone morphogenic proteins (BMPs) play a key role in skeletal development and patterning. Using the technique of differential display polymerase chain reaction (ddPCR), we have identified a novel gene whose expression is increased during BMP-2-induced differentiation of the prechondroblastic cell line, MLB13MYC clone 17, to an osteoblastic phenotype. The 6.5-kilobase mRNA recognized by this ddPCR product is increased 10-fold by BMP-2 treatment of the MLB13MYC clone 17 cells. The mRNA recognized by this ddPCR product is also increased as MC3T3-E1 cells recapitulate the program of osteoblast differentiation during prolonged culture. The full-length transcript corresponding to this ddPCR product was cloned from a MLB13MYC clone 17 cell cDNA library. Analysis of the deduced amino acid sequence demonstrated that this gene encodes a novel 126-kDa putative serine/threonine protein kinase containing a nuclear localization signal. The kinase domain, expressed in Escherichia coli, is capable of autophosphorylation as well as phosphorylation of myelin basic protein. The gene was, therefore, named BIKe (BMP-2-Inducible Kinase). The BIKe nuclear localization signal is able to direct green fluorescent protein to the nucleus in transfected COS-7 cells. When stably expressed in MC3T3-E1 cells, BIKe significantly decreases alkaline phosphatase activity and osteocalcin mRNA levels and retards mineral deposition relative to vector control. This novel kinase, therefore, is likely to play an important regulatory role in attenuating the program of osteoblast differentiation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Div Endocrinol Diabet Metab & Nutr, Rochester, MN 55905 USA. RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Wellman 503,50 Blossom St, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR-45011]; NIDDK NIH HHS [DK-36597] NR 38 TC 28 Z9 30 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 NOV 9 PY 2001 VL 276 IS 45 BP 42213 EP 42218 DI 10.1074/jbc.M106163200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400090 PM 11500515 ER PT J AU Zhang, LJ Beeler, DL Lawrence, R Lech, M Liu, J Davis, JC Shriver, Z Sasisekharan, R Rosenberg, RD AF Zhang, LJ Beeler, DL Lawrence, R Lech, M Liu, J Davis, JC Shriver, Z Sasisekharan, R Rosenberg, RD TI 6-O-sulfotransferase-1 represents a critical enzyme in the anticoagulant heparan sulfate biosynthetic pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID D-GLUCOSAMINYL 3-O-SULFOTRANSFERASE; HAMSTER OVARY CELLS; ANTITHROMBIN-BINDING SEQUENCE; EMBRYONAL CARCINOMA-CELLS; HUMAN CDNAS; PROTEOGLYCANS; MUTANTS; RESIDUES; EXPRESSION; ACID AB Using recombinant retroviral transduction, we have introduced the heparin/heparan sulfate (HS) 3-O-sulfotransferase I (3-OST-1) gene into Chinese hamster ovary (CHO) cells. Expression of 3-OST-1 confers upon CHO cells the ability to produce anticoagulantly active HS (HSact). To understand how 6-OST and other proteins regulate HSact biosynthesis, a CHO cell clone with three copies of 3-OST-1 was chemically mutagenized. Resulting mutants that make HS but are defective in generating HSact were single-cell-cloned. One cell mutant makes fewer 6-O-sulfated residues. Modification of HS chains from the mutant with pure 6-OST-1 and 3'-phosphoadenosine 5'-phosphosulfate increased HSact from 7% to 51%. Transfection of this mutant with 6-OST-1 created a CHO cell line that makes HS, 50% of which is HSact. We discovered in this study that M 6-OST-1 is a limiting enzyme in the HSact biosynthetic pathway in vivo when the limiting nature of 3-OST-1 is removed; (ii) HS chains from the mutant cells serve as an excellent substrate for demonstrating that 6-OST-1 is the limiting factor for Hs(act) generation in vitro; (iii) in contradiction to the literature, 6-OST-1 can add 6-O-sulfate to GlcNAc residues, especially the critical 6-O-sulfate in the antithrombin binding motif; (iv) both 3-O- and 6-O-sulfation can be the final step in HSact biosynthesis in contrast to prior publications that concluded 3-O-sulfation is the final step in HSact biosynthesis; (v), in the presence of HS interacting protein peptide, 3-O-sulfate-containing sugars can be degraded into disaccharides by heparitinase digestion as demonstrated by capillary high performance liquid chromatography coupled with mass spectrometry. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Div Bioengn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, BIDMC, Dept Med, Boston, MA 02215 USA. RP Rosenberg, RD (reprint author), MIT, Dept Biol, 77 Massachusetts Ave,Bldg 68-480, Cambridge, MA 02139 USA. FU NHLBI NIH HHS [5-R01-HL-58479, 5-P01-HL41484]; NIGMS NIH HHS [GM-50573] NR 42 TC 48 Z9 49 U1 2 U2 6 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 NOV 9 PY 2001 VL 276 IS 45 BP 42311 EP 42321 DI 10.1074/jbc.M101441200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400102 PM 11551899 ER PT J AU Gooch, JL Tang, YP Ricono, JM Abboud, HE AF Gooch, JL Tang, YP Ricono, JM Abboud, HE TI Insulin-like growth factor-I induces renal cell hypertrophy via a calcineurin-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID URINARY ALBUMIN EXCRETION; MESANGIAL CELLS; CARDIAC-HYPERTROPHY; TRANSGENIC MICE; HORMONE; RECEPTOR; EXPRESSION; SYSTEM; NFAT AB Insulin-like growth factor-I (IGF-I) may play an important role in the development of renal hypertrophy. In this study we determined the effect of IGF-I on cultured mesangial cells (MCs) and examined activation of key signaling pathways. IGF-I induced hypertrophy as determined by an increase in cell size and an increase in protein to DNA ratio and increased accumulation of extracellular matrix (ECM) proteins. IGF-I also activated both Erk1/Erk2 MAPK and phosphatidylinositol 3-kinase (PI3K) in MCs. Inhibition of either MAPK or PI3K, however, had no effect on IGF-I-induced hypertrophy or ECM production. Next, we examined the effect of IGF-I on activation of the calcium-dependent phosphatase calcineurin. IGF-I treatment stimulated calcineurin activity and increased the protein levels of calcineurin and the calcineurin binding protein, calmodulin. Cyclosporin A, an inhibitor of calcineurin, blocked both IGF-I-mediated hypertrophy and up-regulation of ECM. In addition, calcineurin resulted in sustained Akt activation, indicating possible cross-talk with other signaling pathways. Finally, IGF-I treatment resulted in the calcineurindependent nuclear localization of NFATc1. Therefore, IGF-I induces hypertrophy and increases ECM accumulation in MCs. IGF-I-mediated hypertrophy is associated with activation of Erk1/Erk2 MAPK and PI3K but does not require either of these pathways. Instead, IGF-I mediates hypertrophy via a calcineurin-dependent pathway. C1 Univ Texas, Hlth Sci Ctr, Dept Med Nephrol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78229 USA. RP Gooch, JL (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 36 TC 56 Z9 61 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 NOV 9 PY 2001 VL 276 IS 45 BP 42492 EP 42500 DI 10.1074/jbc.M102994200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400122 PM 11509557 ER PT J AU Song, CS Echchgadda, I Baek, BS Ahn, SC Oh, T Roy, AK Chatterjee, B AF Song, CS Echchgadda, I Baek, BS Ahn, SC Oh, T Roy, AK Chatterjee, B TI Dehydroepiandrosterone sulfotransferase gene induction by bile acid activated farnesoid X receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT-LIVER; MOLECULAR-CLONING; STRUCTURAL CHARACTERIZATION; NUCLEAR RECEPTORS; ANDROGEN; PROTEIN; BINDING; IDENTIFICATION; EXPRESSION; PROMOTER AB Dehydroepiandrosterone sulfotransferase (STD) is a hydroxysteroid sulfo-conjugating enzyme with preferential substrate specificity for C-19 androgenic steroids and C-24 bile acids. STD is primarily expressed in the liver, intestine and adrenal cortex. Earlier studies have shown that androgens inhibit the rat Std promoter function through a negative androgen response region located between -235 and -310 base pair positions (Song, C. S., Jung, M. H., Kim, S. C., Hassan, T., Roy, A. K., and Chatterjee, B. (1998) J. Biol Chem. 273, 21856-21866). Here we report that the primary bile acid chenodeoxycholic acid (CDCA) also acts as an important regulator of the Std gene promoter. CDCA is a potent inducer of the Std gene, and its inducing effect is mediated through the bile acid-activated farnesoid X receptor (FXR), a recently characterized member of the nuclear receptor superfamily. The ligand-activated FXR acts as a heterodimer with the 9-cis-retinoic acid receptor (RXR) and regulates the Std gene by binding to an upstream region at base pair positions -169 to -193. This specific binding region was initially identified by bile acid responsiveness of the progressively deleted forms of the Std promoter in transfected HepG2 hepatoma and enterocyte-like Caco-2 cells. Subsequently, the precise RXR/FXR binding position was established by protein-DNA interaction using in vitro footprinting and electrophoretic mobility shift analyses. Unlike all other previously characterized FXR target genes, which contain an inverted repeat (IR) of the consensus hexanucleotide half-site (A/G)G(G/T)TCA with a single nucleotide spacer (IR-1), the bile acid response element of the Std promoter does not contain any spacer between the two hexanucleotide repeats (IR-0). A promoter-reporter construct carrying three tandem copies of the IR-0 containing -169/-193 element, linked to a minimal thymidine kinase promoter, can be stimulated more than 70-fold in transfected Caco-2 cells upon CDCA treatment. Autoregulation of the STD gene by its bile acid substrate may provide an important contributing role in the enterohepatic bile acid metabolism and cholesterol homeostasis. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Chatterjee, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [AG-10486] NR 44 TC 143 Z9 143 U1 0 U2 4 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 NOV 9 PY 2001 VL 276 IS 45 BP 42549 EP 42556 DI 10.1074/jbc.M107557200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 497HY UT WOS:000172450400130 PM 11533040 ER PT J AU Kaunitz, JD Akiba, Y AF Kaunitz, JD Akiba, Y TI Integrated duodenal protective response to acid SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Symposium on Cell/Tissue Injury and Cytoprotection/Organoprotection CY FEB 24-27, 2000 CL LONG BEACH, CALIFORNIA DE bicarbonate secretion; mucosal defense; hydrochloric acid; blood flow; mucus secretion; mucus gel thickness ID GENE-RELATED PEPTIDE; GASTRIC HYPEREMIC RESPONSE; CYSTIC-FIBROSIS; BICARBONATE SECRETION; HELICOBACTER-PYLORI; MUCOSAL PROTECTION; ANION-EXCHANGER; HCO3 SECRETION; RAT DUODENUM; PH GRADIENTS AB The proximal duodenum is unique in that it is the only leaky epithelium regularly exposed to concentrated gastric acid. To prevent injury from occurring, numerous duodenal defense mechanisms have evolved. The most studied is bicarbonate secretion, which is presumed to neutralize luminal acid. Less well studied in their protective roles are the mucus gel layer and blood flow. Measuring duodenal epithelial intracellular pH [pH(i)], blood flow and mucus gel thickness (MGT), we studied duodenal defense mechanisms in vivo so as to more fully understand the mucosal response to luminal acid. Exposure of the mucosa to physiologic acid solutions promptly lowered pH(i), followed by recovery after acid was removed, indicating that acid at physiologic concentrations readily diffuses into, but does not damage duodenal epithelial cells. Cellular acid then exits the cell via an amiloride-inhibitable process, presumably sodium-proton exchange (NHE). MGT and blood flow increase promptly during acid perfusion; both decrease after acid challenge and are inhibited by vanilloid receptor antagonists or by sensory afferent denervation. Bicarbonate secretion is not affected by acid superfusion but increases after challenge. Inhibition of cellular base loading lowers pH(i), whereas inhibition of apical base extrusion alkalinizes pH(i). These observations support the following hypothesis: luminal acid diffuses into the epithelial cells, lowering pH(i). Acidic pH(i) increases the activity of a basolateral NHE, acidifying the submucosal space and increasing cellular base loading. The acidic submucosal space activates capsaicin receptors on afferent nerves, increasing MGT and blood flow. With concontinued acid exposure, a new steady state with thickened mucus gel, increased blood flow, and a higher cellular buffering power protects against acid injury. After acid challenge, mucus secretion decreases, blood flow slows, and pH(i) returns to normal, the latter occurring via apical bicarbonate extrusion, increasing bicarbonate secretion. Through these integrated mechanisms, the epithelial cells are protected from damage due to repeated pulses of concentrated gastric acid. Published by Elsevier Science Inc. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Keio Univ, Sch Med, Dept Internal Med, Div Gastroenterol & Hepatol,Shinjuku Ku, Tokyo 1608582, Japan. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Hlth Care Syst, 11301 Wilshire Blvd,Bldg 114,Suite 217, Los Angeles, CA 90073 USA. NR 41 TC 12 Z9 17 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD NOV 9 PY 2001 VL 69 IS 25-26 BP 3073 EP 3081 DI 10.1016/S0024-3205(01)01413-8 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 493YR UT WOS:000172251500012 PM 11758832 ER PT J AU Fishman, MC AF Fishman, MC TI Genomics - Zebrafish - The canonical vertebrate SO SCIENCE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Cardiovasc, Boston, MA 02114 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 140 Z9 148 U1 1 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 9 PY 2001 VL 294 IS 5545 BP 1290 EP 1291 DI 10.1126/science.1066652 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 491VF UT WOS:000172130200030 PM 11701913 ER PT J AU Zhong, TP Childs, S Leu, JP Fishman, MC AF Zhong, TP Childs, S Leu, JP Fishman, MC TI Gridlock signalling pathway fashions the first embryonic artery SO NATURE LA English DT Article ID EARLY EMBRYOGENESIS; REPRESSOR PROTEINS; NOTCH; ZEBRAFISH; TRANSCRIPTION; HAIRY; ENHANCER; HOMOLOG; SPLIT; GENES AB Arteries and veins are morphologically, functionally and molecularly very different, but how this distinction is established during vasculogenesis is unknown(1,2). Here we show, by lineage tracking in zebrafish embryos, that angioblast precursors for the trunk artery and vein are spatially mixed in the lateral posterior mesoderm. Progeny of each angioblast, however, are restricted to one of the vessels. This arterial-venous decision is guided by gridlock (grl), an artery-restricted gene that is expressed in the lateral posterior mesoderm(3). Graded reduction of grl expression, by mutation or morpholino antisense, progressively ablates regions of the artery, and expands contiguous regions of the vein, preceded by an increase in expression of the venous marker EphB4 receptor (ephb4)(2) and diminution of expression of the arterial marker ephrin-B2 (efnb2)(2). grl is downstream of notch(4), and interference with notch signalling, by blocking Su(H)(4), similarly reduces the artery and increases the vein. Thus, a notch-grl pathway controls assembly of the first embryonic artery, apparently by adjudicating an arterial versus venous cell fate decision. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. NR 30 TC 351 Z9 367 U1 4 U2 14 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 8 PY 2001 VL 414 IS 6860 BP 216 EP 220 DI 10.1038/35102599 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490AY UT WOS:000172029100050 PM 11700560 ER PT J AU Pannifer, AD Wong, TY Schwarzenbacher, R Renatus, M Petosa, C Bienkowska, J Lacy, DB Collier, RJ Park, S Leppla, SH Hanna, P Liddington, RC AF Pannifer, AD Wong, TY Schwarzenbacher, R Renatus, M Petosa, C Bienkowska, J Lacy, DB Collier, RJ Park, S Leppla, SH Hanna, P Liddington, RC TI Crystal structure of the anthrax lethal factor SO NATURE LA English DT Article ID PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; FACTOR CLEAVES; TOXIN; MACROPHAGES; PROTEIN; IDENTIFICATION; PROGRAM AB Lethal factor (LF) is a protein (relative molecular mass 90,000) that is critical in the pathogenesis of anthrax(1-3). It is a highly specific protease that cleaves members of the mitogen-activated protein kinase kinase (MAPKK) family near to their amino termini, leading to the inhibition of one or more signalling pathways(4-6). Here we describe the crystal structure of LF and its complex with the N terminus of MAPKK-2. LF comprises four domains: domain I binds the membrane-translocating component of anthrax toxin, the protective antigen (PA); domains II, III and IV together create a long deep groove that holds the 16-residue N-terminal tail of MAPKK-2 before cleavage. Domain II resembles the ADP-ribosylating toxin from Bacillus cereus, but the active site has been mutated and recruited to augment substrate recognition. Domain III is inserted into domain II, and seems to have arisen from a repeated duplication of a structural element of domain II. Domain IV is distantly related to the zinc metalloprotease family, and contains the catalytic centre; it also resembles domain I. The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity. C1 Burnham Inst, La Jolla, CA 92037 USA. Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. RP Liddington, RC (reprint author), Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI Collier, R John/0000-0002-2427-4239 NR 31 TC 278 Z9 295 U1 2 U2 19 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 8 PY 2001 VL 414 IS 6860 BP 229 EP 233 DI 10.1038/n35101998 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490AY UT WOS:000172029100053 PM 11700563 ER PT J AU Ma, JX Znoiko, S Othersen, KL Ryan, JC Das, J Isayama, T Kono, M Oprian, DD Corson, DW Cornwall, MC Cameron, DA Harosi, FI Makino, CL Crouch, RK AF Ma, JX Znoiko, S Othersen, KL Ryan, JC Das, J Isayama, T Kono, M Oprian, DD Corson, DW Cornwall, MC Cameron, DA Harosi, FI Makino, CL Crouch, RK TI A visual pigment expressed in both rod and cone photoreceptors SO NEURON LA English DT Article ID TIGER SALAMANDER RETINA; PROTEIN BETA-SUBUNIT; MOLECULAR-CLONING; LINEAR DICHROISM; BOVINE RHODOPSIN; GAMMA-SUBUNIT; DARK NOISE; CELLS; GREEN; IDENTIFICATION AB Rods and cones contain closely related but distinct G protein-coupled receptors, opsins, which have diverged to meet the differing requirements of night and day vision. Here, we provide evidence for an exception to that rule. Results from immunohistochemistry, spectrophotometry, and single-cell RT-PCR demonstrate that, in the tiger salamander, the green rods and blue-sensitive cones contain the same opsin. In contrast, the two cells express distinct G protein transducin a subunits: rod a transducin in green rods and cone a transducin in blue-sensitive cones. The different transducins do not appear to markedly affect photon sensitivity or response kinetics in the green rod and blue-sensitive cone. This suggests that neither the cell topology or the transducin is sufficient to differentiate the rod and the cone response. C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol, Charleston, SC 29425 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Brandeis Univ, Volen Ctr Complex Syst, Waltham, MA 02454 USA. Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA. Boston Univ, Sch Med, Dept Physiol, Boston, MA 02118 USA. Marine Biol Lab, Lab Sensory Physiol, Woods Hole, MA 02543 USA. RP Ma, JX (reprint author), Med Univ S Carolina, Dept Ophthalmol, 171 Ashley Ave, Charleston, SC 29425 USA. RI Znoyko, Sergey/E-1294-2013; OI Znoyko, Sergey/0000-0003-1265-328X; Ryan, James/0000-0002-1101-3785 FU NEI NIH HHS [EY04876, EY04939, EY07543, EY12231, EY12600, P30 EY12196, EY01157, EY11358, R01 EY009514] NR 62 TC 66 Z9 68 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 8 PY 2001 VL 32 IS 3 BP 451 EP 461 DI 10.1016/S0896-6273(01)00482-2 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 491QE UT WOS:000172119100011 PM 11709156 ER PT J AU Aharon, I Etcoff, N Ariely, D Chabris, CF O'Connor, E Breiter, HC AF Aharon, I Etcoff, N Ariely, D Chabris, CF O'Connor, E Breiter, HC TI Beautiful faces have variable reward value: fMRI and behavioral evidence SO NEURON LA English DT Article ID DIFFERENTIAL NEURAL RESPONSE; FACIAL ATTRACTIVENESS; SELF-STIMULATION; HUMAN BRAIN; INFANT PREFERENCES; PREFRONTAL CORTEX; DECISION-MAKING; HUMAN AMYGDALA; EXPRESSION; FOREBRAIN AB The brain circuitry processing rewarding and aversive stimuli is hypothesized to be at the core of motivated behavior. In this study, discrete categories of beautiful faces are shown to have differing reward values and to differentially activate reward circuitry in human subjects. In particular, young heterosexual males rate pictures of beautiful males and females as attractive, but exert effort via a keypress procedure only to view pictures of attractive females. Functional magnetic resonance imaging at 3 T shows that passive viewing of beautiful female faces activates reward circuitry, in particular the nucleus accumbens. An extended set of subcortical and paralimbic reward regions also appear to follow aspects of the keypress rather than the rating procedures, suggesting that reward circuitry function does not include aesthetic assessment. C1 Massachusetts Gen Hosp, Dept Radiol, Motivat & Emot Neurosci Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Breiter, HC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Motivat & Emot Neurosci Ctr, Boston, MA 02129 USA. FU PHS HHS [00265, 09467] NR 76 TC 524 Z9 541 U1 15 U2 100 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 8 PY 2001 VL 32 IS 3 BP 537 EP 551 DI 10.1016/S0896-6273(01)00491-3 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 491QE UT WOS:000172119100018 PM 11709163 ER PT J AU Astuti, D Agathanggelou, A Honorio, S Dallol, A Martinsson, T Kogner, P Cummins, C Neumann, HPH Voutilainen, R Dahia, P Eng, C Maher, ER Latif, F AF Astuti, D Agathanggelou, A Honorio, S Dallol, A Martinsson, T Kogner, P Cummins, C Neumann, HPH Voutilainen, R Dahia, P Eng, C Maher, ER Latif, F TI RASSF1A promoter region CpG island hypermethylation in phaeochromocytomas and neuroblastoma tumours SO ONCOGENE LA English DT Article DE methylation; 3p tumour suppressor gene; neuroblastoma; phaeochromocytoma ID HOMOZYGOUS DELETION; LUNG-CANCER; GENE-EXPRESSION; SHORT ARM; SUPPRESSOR; PHEOCHROMOCYTOMA; HETEROZYGOSITY; IDENTIFICATION; TUMORS; CHROMOSOME-3 AB Deletions of chromosome 3p are frequent in many types of neoplasia including neural crest tumours such as neuroblastoma (NB) and phaeochromocytoma. Recently we isolated several candidate tumour suppressor genes (TSGs) from a 120 kb critical interval at 3p21.3 defined by overlapping homozygous deletions in lung and breast tumour lines. Although mutation analysis of candidate TSGs in lung and breast cancers revealed only rare mutations, expression of one of the genes (RASSF1A) was absent in the majority of lung tumour cell lines analysed. Subsequently methylation of a CpG island in the promoter region of RASSF1A was demonstrated in a majority of small cell lung carcinomas and to a lesser extent in non-small cell lung carcinomas. To investigate the role of 3p TSGs in neural crest tumours, we (a) analysed phaeochromocytomas for 3p allele loss (n = 41) and RASSF1A methylation (n = 23) and (b) investigated 67 neuroblastomas for RASSF1A inactivation. 46% of phaeochromocytomas showed 3p allele loss (38.5% at 3p21.3). RASSF1A promoter region hypermethylation was found in 22% (5/23) of sporadic phaeochromocytomas and in 55% (37/67) of neuroblastomas analysed but RASSF1A mutations were not identified. In two neuroblastoma cell lines, methylation of RASSF1A correlated with loss of RASSF1A expression and RASSF1A expression was restored after treatment with the demethylating agent 5-azacytidine. As frequent methylation of the CASP8 gene has also been reported in neuroblastoma, we investigated whether RASSF1A and CASP8 methylation were independent or related events. CASP8 methylation was detected in 56% of neuroblastomas with RASSF1A methylation and 17% without RASSF1A methylation (P = 0.0031). These results indicate that (a) RASSF1A inactivation by hypermethylation is a frequent event in neural crest tumorigenesis, particularly neuroblastoma, and that RASSF1A is a candidate 3p21.3 neuroblastoma TSG and (b) a subset of neuroblastomas may be characterized by a CpG island methylator phenotype. C1 Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. Univ Gothenburg, Sahlgrenska Univ Hosp Ostra, Dept Clin Genet, S-41685 Gothenburg, Sweden. Karolinska Inst, Karolinska Hosp, Dept Woman & Child Hlth, Childhood Canc Res Unit, S-17176 Stockholm, Sweden. Birmingham Childrens Hosp, Birmingham, W Midlands, England. Univ Freiburg, Med Klin, D-79106 Freiburg, Germany. Kuopio Univ Hosp, Dept Pediat, FIN-70211 Kuopio, Finland. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge, England. RP Latif, F (reprint author), Univ Birmingham, Sch Med, Dept Paediat & Child Hlth, Sect Med & Mol Genet, Birmingham B15 2TT, W Midlands, England. RI MAHER, EAMONN/A-9507-2008; Dallol, Ashraf/H-8661-2012; Martinsson, Tommy/J-4140-2013; OI MAHER, EAMONN/0000-0002-6226-6918; Dallol, Ashraf/0000-0002-8803-228X; Martinsson, Tommy/0000-0002-9403-3123; Cummins, Carole/0000-0001-5464-1944; Eng, Charis/0000-0002-3693-5145 NR 27 TC 96 Z9 103 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 8 PY 2001 VL 20 IS 51 BP 7573 EP 7577 DI 10.1038/sj.onc.1204968 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 489DN UT WOS:000171976900014 PM 11709729 ER PT J AU Post, S Weng, YC Cimprich, K Chen, LB Xu, Y Lee, EYHP AF Post, S Weng, YC Cimprich, K Chen, LB Xu, Y Lee, EYHP TI Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for G(1)/S checkpoint activation in response to DNA damage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EARLY EMBRYONIC LETHALITY; REPLICATION-FACTOR-C; ATAXIA-TELANGIECTASIA; SCHIZOSACCHAROMYCES-POMBE; CHROMOSOMAL FRAGMENTATION; TARGETED DISRUPTION; IONIZING-RADIATION; BUDDING YEAST; SLIDING CLAMP; CDNA CLONING AB ATR [ataxia-telangiectasia-mutated (ATM)- and Rad3-related] is a protein kinase required for both DNA damage-induced cell cycle checkpoint responses and the DNA replication checkpoint that prevents mitosis before the completion of DNA synthesis. Although ATM and ATR kinases share many substrates, the different phenotypes of ATM- and ATR-deficient mice indicate that these kinases are not functionally redundant. Here we demonstrate that ATR but not ATM phosphorylates the human Rad17 (hRad17) checkpoint protein on Ser(635) and Ser(545) in vitro. In undamaged synchronized human cells, these two sites were phosphorylated in late G(1), S, and G(2)/M, but not in early-mid G1. Treatment of cells with genotoxic stress induced phosphorylation of hRad17 in cells in early-mid G1. Expression of kinase-inactive ATR resulted in reduced phosphorylation of these residues, but these same serine residues were phosphorylated in ionizing radiation (IR)-treated ATM-deficient human cell lines. IR-induced phosphorylation of hRad17 was also observed in ATM-deficient tissues, but induction of Ser(645) was not optimal. Expression of a hRad17 mutant, with both serine residues changed to alanine, abolished IR-induced activation of the G(1)/S checkpoint in MCF-7 cells. These results suggest ATR and hRad17 are essential components of a DNA damage response pathway in mammalian cells. C1 Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78245 USA. Stanford Univ, Dept Mol Pharmacol, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, EYHP (reprint author), Univ Calif San Diego, Dept Biol, 9500 Gilman Dr, La Jolla, CA 92093 USA. FU NCI NIH HHS [P01CA81020, P01 CA081020] NR 49 TC 48 Z9 51 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2001 VL 98 IS 23 BP 13102 EP 13107 DI 10.1073/pnas.231364598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490WM UT WOS:000172076800050 PM 11687627 ER PT J AU Geng, Y Yu, QY Whoriskey, W Dick, F Tsai, KY Ford, HL Biswas, DK Pardee, AB Amati, B Jacks, T Richardson, A Dyson, N Sicinski, P AF Geng, Y Yu, QY Whoriskey, W Dick, F Tsai, KY Ford, HL Biswas, DK Pardee, AB Amati, B Jacks, T Richardson, A Dyson, N Sicinski, P TI Expression of cyclins E1 and E2 during mouse development and in neoplasia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-CYCLE; S-PHASE; FAMILY PROTEINS; PRB/E2F PATHWAY; TRANSGENIC MICE; BREAST-CANCER; E GENE; TRANSCRIPTION; G(1); CDK2 AB Cyclin E1 (formerly called cyclin E) and the recently described cyclin E2 belong to the family of E-type cyclins that operate during the G(1)/S phase progression in mammalian cells. The two E-cyclins share a catalytic partner, cyclin-dependent kinase 2 (CDK2), and activate their associated kinase activities at similar times during cell cycle progression. Despite these similarities, it is unknown whether the two proteins perform distinct functions, or, alternatively, they control S-phase entry of different cell types in a tissue-specific fashion. To start addressing in vivo functions of E-cyclins, we determined the expression pattern of cyclins E1 and E2 during normal mouse development. We found that the two E-cyclins showed very similar patterns of expression; both were expressed within the proliferating compartment during embryo development. Analyses of cells and tissues lacking members of the retinoblastoma (pRB) family of proteins revealed that the expression of both cyclins is controlled in a pRB-dependent, but p107- and p130-independent fashion, likely through the pRB-dependent E2F transcription factors. We also found that cyclins E1 and E2 are expressed at high levels in mouse breast tumors driven by the Myc oncogene. Last, we found that cyclin E2 is overexpressed in approximate to 24% of analyzed human mammary carcinomas. Collectively these findings suggest that the expression of cyclins E1 and E2 is governed by similar molecular circuitry. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80262 USA. DNAX Res Inst Mol & Cellular Biol Inc, Dept Oncol, Palo Alto, CA 94304 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sicinski, P (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA83688-01, R01 CA083688] NR 35 TC 50 Z9 55 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2001 VL 98 IS 23 BP 13138 EP 13143 DI 10.1073/pnas.231487798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490WM UT WOS:000172076800056 PM 11687642 ER PT J AU Cornet, A Savidge, TC Cabarrocas, J Deng, WL Colombel, JF Lassmann, H Desreumaux, P Liblau, RS AF Cornet, A Savidge, TC Cabarrocas, J Deng, WL Colombel, JF Lassmann, H Desreumaux, P Liblau, RS TI Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease? SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CENTRAL-NERVOUS-SYSTEM; ADULT TRANSGENIC MICE; T-CELLS; REACTIVE ASTROCYTES; ANTIGEN PRESENTATION; ULCERATIVE-COLITIS; IFN-GAMMA; PROTEIN; INDUCTION AB Early pathological manifestations of Crohn's disease (CID) include vascular disruption, T cell infiltration of nerve plexi, neuronal degeneration, and induction of T helper 1 cytokine responses. This study demonstrates that disruption of the enteric glial cell network in CID patients represents another early pathological feature that may be modeled after CD8(+) T cell-mediated autoimmune targeting of enteric glia in double transgenic mice. Mice expressing a viral neoself antigen in astrocytes and enteric glia were crossed with specific T cell receptor transgenic mice, resulting in apoptotic depletion of enteric glia to levels comparable in CD patients. Intestinal and mesenteric T cell infiltration, vasculitis, T helper 1 cytokine production, and fulminant bowel inflammation were characteristic hallmarks of disease progression. Immune-mediated damage to enteric glia therefore may participate in the initiation and/or the progression of human inflammatory bowel disease. C1 Univ Paris 06, INSERM U546, F-75013 Paris, France. Univ Paris 06, Immunol Lab, F-75013 Paris, France. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. CHU Lille, INSERM, Equipe Mixte, Inflammatory Bowel Dis Lab, F-59000 Lille, France. Univ Vienna, Brain Res Inst, Dept Neuroimmunol, A-1090 Vienna, Austria. RP Liblau, RS (reprint author), Univ Paris 06, INSERM U546, 105 Blvd Hop, F-75013 Paris, France. FU NICHD NIH HHS [R01-HD31852, R01 HD031852, R37 HD012437, R37-HD12437]; NIDDK NIH HHS [P01 DK033506, P01-DK33506, P30 DK040561, P30-DK40561] NR 48 TC 150 Z9 153 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2001 VL 98 IS 23 BP 13306 EP 13311 DI 10.1073/pnas.231474098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 490WM UT WOS:000172076800085 PM 11687633 ER PT J AU Palframan, RT Jung, S Cheng, CY Weninger, W Luo, Y Dorf, M Littman, DR Rollins, BJ Zweerink, H Rot, A von Andrian, UH AF Palframan, RT Jung, S Cheng, CY Weninger, W Luo, Y Dorf, M Littman, DR Rollins, BJ Zweerink, H Rot, A von Andrian, UH TI Inflammatory chemokine transport and presentation in HEV: A remote control mechanism for monocyte recruitment to lymph nodes in inflamed tissues SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE homing; MCP-1; high endothelial venules; phagocytes; lymphatic system ID HIGH ENDOTHELIAL VENULES; DENDRITIC CELLS; CHEMOATTRACTANT PROTEIN-1; KNOCKOUT MICE; T-LYMPHOCYTES; MACROPHAGES; MIGRATION; EXPRESSION; ADHESION; CCR2 AB Interstitial fluid is constantly drained into lymph nodes (LNs) via afferent lymph vessels. This conduit enables monocyte-derived macrophages and dendritic cells to access LNs from peripheral tissues. We show that during inflammation in the skin, a second recruitment pathway is evoked that recruits large numbers of blood-borne monocytes to LNs via high endothelial venules (HEVs). Inhibition of monocyte chemoattractant protein (MCP)-1 blocked this inflammation-induced monocyte homing to LNs. MCP-1 mRNA in inflamed skin was over 100-fold upregulated and paralleled MCP-1 protein levels, whereas in draining LNs MCP-1 mRNA induction was much weaker and occurred only after a pronounced rise in MCP-1 protein. Thus, MCP-1 in draining LNs was primarily derived from inflamed skin. In MCP-1(-/-) mice, intracutaneously injected MCP-I accumulated rapidly in the draining LNs where it enhanced monocyte recruitment. Intravital microscopy showed that skin-derived MCP-1 was transported via the lymph to the luminal surface of HEVs where it triggered integrin-dependent arrest of rolling monocytes. These findings demonstrate that inflamed peripheral tissues project their local chemokine profile to HEVs in draining LNs and thereby exert "remote control" over the composition of leukocyte populations that home to these organs from the blood. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NYU, Sch Med, Skirball Inst Biomol Med, Mol Pathogenesis Program, New York, NY 10016 USA. NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA. Merck Res Labs, Rahway, NJ 07065 USA. Novartis Forschungsinst, A-1235 Vienna, Austria. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008; OI Jung, Steffen/0000-0003-4290-5716 FU NHLBI NIH HHS [HL54936, HL56949, HL62524, P01 HL056949, R01 HL054936]; NIAMS NIH HHS [AR42689, P30 AR042689] NR 53 TC 319 Z9 325 U1 0 U2 12 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 NOV 5 PY 2001 VL 194 IS 9 BP 1361 EP 1373 DI 10.1084/jem.194.9.1361 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 492GF UT WOS:000172159500016 PM 11696600 ER PT J AU Barry, MJ Roehrborn, CG AF Barry, MJ Roehrborn, CG TI Extracts from "Clinical Evidence" - Benign prostatic hyperplasia SO BRITISH MEDICAL JOURNAL LA English DT Review ID ACUTE URINARY RETENTION; RANDOMIZED CONTROLLED TRIAL; TRANSURETHRAL MICROWAVE THERMOTHERAPY; COMPLEX URODYNAMIC ASSESSMENT; SUSTAINED-RELEASE ALFUZOSIN; 1-YEAR FOLLOW-UP; NATURAL-HISTORY; DOUBLE-BLIND; LASER-ABLATION; SEXUAL FUNCTION C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Gen Med Unit, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Urol, Dallas, TX 75235 USA. RP Roehrborn, CG (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Gen Med Unit, Boston, MA 02114 USA. NR 57 TC 36 Z9 36 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD NOV 3 PY 2001 VL 323 IS 7320 BP 1042 EP 1046 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 490MP UT WOS:000172055900021 PM 11691764 ER PT J AU Hu, H Rudd, CE Schneider, H AF Hu, H Rudd, CE Schneider, H TI Src kinases Fyn and Lck facilitate the accumulation of phosphorylated CTLA-4 and its association with PI-3 kinase in intracellular compartments of T-cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LYMPHOCYTE-ASSOCIATED MOLECULE-4; CLATHRIN-ASSOCIATED PROTEIN; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; CYTOPLASMIC TAIL; DISTINCT ROLES; MICE LACKING; CD28; ACTIVATION; RECEPTOR AB Src kinases bind to surface receptors and mediate signaling events at the surface of cells. Little is known regarding whether these kinases can mediate events within intracellular compartments. The T-cell antigen CTLA-4 resides primarily in the trans-Golgi network (TGN), and as such could serve as a model to study the intracellular function of src kinases in their ability to phosphorylate the receptor. In this study, we show that tyrosine kinases p56(lck) and p59(fyn) phosphorylate the cytoplasmic domain of CTLA-4 in T-cells. Most interestingly, these kinases are also found in the Golgi apparatus, the intracellular compartment where most of CTLA-4 is localized. Transfection of Lek or Fyn resulted in increased phosphorylation of intracellular CTLA-4 and recruitment of PI-3 kinase. By contrast, phosphorylation did not influence the presence of the receptor in the TGN. These data demonstrate that src kinases operate to modulate receptor binding to intracellular signaling proteins introducing the possibility that intracellular forms of receptors may generate growth signals. (C) 2001 Academic Press. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Fac Med, Dept Haematol, London W12 0NN, England. RP Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM helga.schneider@ic.ac.uk NR 38 TC 17 Z9 17 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 2 PY 2001 VL 288 IS 3 BP 573 EP 578 DI 10.1006/bbrc.2001.5814 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 490WW UT WOS:000172077500013 PM 11676481 ER PT J AU Suzuki, T Ganesh, S Agarwala, KL Morita, R Sugimoto, Y Inazawa, J Delgado-Escueta, AV Yamakawa, K AF Suzuki, T Ganesh, S Agarwala, KL Morita, R Sugimoto, Y Inazawa, J Delgado-Escueta, AV Yamakawa, K TI A novel gene in the chromosomal region for juvenile myoclonic epilepsy on 6p12 encodes a brain-specific lysosomal membrane protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE lysosomal membrane protein; brain; epilepsy; JME ID IDIOPATHIC GENERALIZED EPILEPSY; LOCUS; STORAGE; LINKAGE; HETEROGENEITY; ASSOCIATION; CHANNELS; MOUSE AB Juvenile myoclonic epilepsy (JME) is the most frequent and, hence, most important form of hereditary grand mal epilepsy. Genetic linkage, haplotype, and recombination analyses have indicated that 6p11-12 (EJM1) is one of the candidate regions harboring a gene responsible for JME. In efforts to identify a gene responsible for JME, we identified several expressed sequences in the EJM1 critical region. Here we report the identification and characterization of a gene, named C6orf33, in the EJM1 region. Northern blot analysis showed that C6orf33 is predominantly expressed in brain but in mice, testis shows additional transcripts. C6orf33 is predicted to encode a novel similar to 40-kDa membrane protein, LMPB1, that defines a novel protein family by having highly conserved orthologs in eukaryotes and three putative paralogs in human. Biochemical and immunocytochemical studies revealed that LMPB1 is indeed an integral membrane protein that targets to lysosomal structures. LAY-PBI may be involved in specialized lysosomal functions that are unique to brain and testis, and the C6orf33 gene is of interest as a candidate for EJM1. (C) 2001 Academic Press. C1 RIKEN, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 3510198, Japan. Tokyo Med & Dent Univ, Inst Med Res, Div Genet, Dept Mol Cytodenet, Tokyo, Japan. Univ Calif Los Angeles, Sch Med, Comprehens Epilepsy Program, Epilepsy Genet Genom Labs, Los Angeles, CA 90024 USA. VA GLAHS W Los Angeles, Los Angeles, CA USA. RP Yamakawa, K (reprint author), RIKEN, Brain Sci Inst, Neurogenet Lab, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. RI Ganesh, Subramniam/B-4131-2009; Yamakawa, Kazuhiro/N-5050-2015; OI Delgado-Escueta, Antonio V./0000-0002-1581-6999 NR 29 TC 11 Z9 14 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 NOV 2 PY 2001 VL 288 IS 3 BP 626 EP 636 DI 10.1006/bbrc.2001.5825 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 490WW UT WOS:000172077500021 PM 11676489 ER PT J AU Stipp, CS Kolesnikova, TV Hemler, ME AF Stipp, CS Kolesnikova, TV Hemler, ME TI EWI-2 is a major CD9 and CD81 partner and member of a novel Ig protein subfamily SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATITIS-C VIRUS; FELINE IMMUNODEFICIENCY VIRUS; DIPHTHERIA-TOXIN RECEPTOR; MHC CLASS-II; TRANSMEMBRANE-4 SUPERFAMILY; CELL MOTILITY; GROWTH-FACTOR; T-CELLS; IMMUNOGLOBULIN SUPERFAMILY; MEMBRANE-PROTEIN AB A novel Ig superfamily protein, EWI-2, was co-purified with tetraspanin protein CD81 under relatively stringent Brij 96 detergent conditions and identified by mass spectrometric protein sequencing. EWI-2 associated specifically with CD9 and CD81 but not with other tetraspanins or with integrins. Immunodepletion experiments indicated that EWI-2-CD9/CD81 interactions are highly stoichiometric, with similar to 70% of CD9 and CD81 associated with EWI-2 in an embryonic kidney cell line. The EWI-2 molecule was covalently cross-linked (in separate complexes) to both CD81 and CD9, suggesting that association is direct. EWI-2 is part of a novel Ig subfamily that includes EWI-F (F2 alpha receptor regulatory protein (FPRP), CD9P-1), EWI-3 (IgSF3), and EWI-101 (CD101). All four members of this Ig subfamily contain a Glu-Trp-Ile (EWI) motif not seen in other Ig proteins. As shown previously, the EWI-F molecule likewise forms highly proximal, specific, and stoichiometric complexes with CD9 and CD81. Human and murine EWI-2 protein sequences are 91% identical, and transcripts in the two species are expressed in virtually every tissue tested. Thus, EWI-2 potentially contributes to a variety of CD9 and CD81 functions seen in different cell and tissue types. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1430,44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM38903] NR 86 TC 136 Z9 144 U1 0 U2 3 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 NOV 2 PY 2001 VL 276 IS 44 BP 40545 EP 40554 DI 10.1074/jbc.M107338200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488FM UT WOS:000171925600025 PM 11504738 ER PT J AU Ballou, LM Tian, PY Lin, HY Jiang, YP Lin, RZ AF Ballou, LM Tian, PY Lin, HY Jiang, YP Lin, RZ TI Dual regulation of glycogen synthase kinase-3 beta by the alpha(1A)-adrenergic receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; CELL-FATE SPECIFICATION; P70 S6 KINASE; DIFFERENTIAL REGULATION; GLUCOSE-TRANSPORT; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; ALPHA-1-ADRENERGIC RECEPTORS; SIGNALING PATHWAY; COUPLED RECEPTORS; POTENTIAL ROLE AB Catecholamines, acting through adrenergic receptors, play an important role in modulating the effects of insulin on glucose metabolism. Insulin activation of glycogen synthesis is mediated in part by the inhibitory phosphorylation of glycogen synthase kinase-3 (GSK-3). In this study, catecholamine regulation of GSK-3 beta was investigated in Rat-1 fibroblasts stably expressing the alpha (1A)-adrenergic receptor. Treatment of these cells with either insulin or phenylephrine (PE), an al-adrenergic receptor agonist, induced Ser-9 phosphorylation of GSK-3 beta and inhibited GSK-3 beta activity. Insulin-induced GSK-3 beta phosphorylation is mediated by the phosphatidylinositol 3-kinase/Akt signaling pathway. PE treatment does not activate phosphatidylinositol 3-kinase or Akt (Ballou, L. M., Cross, M. E., Huang, S., McReynolds, E. M., Zhang, B. X., and Lin, R. Z. (2000) J. Biol. Chem. 275, 4803-4809), but instead inhibits insulin-induced Akt activation and GSK-3 beta phosphorylation. Experiments using protein kinase C (PKC) inhibitors suggest that phorbol ester-sensitive novel PKC and Go 6983-sensitive atypical PKC isoforms are involved in the PE-induced phosphorylation of GSK-3 beta. Indeed, PE treatment of Rat-1 cells increased the activity of atypical PKC zeta, and expression of PKC zeta in COS-7 cells stimulated GSK-3 beta Ser-9 phosphorylation. In addition, PE-induced GSK-3 beta phosphorylation was reduced in Rat-1 cells treated with a cell-permeable PKC zeta pseudosubstrate peptide inhibitor. These results suggest that the alpha (1A)-adrenergic receptor regulates GSK-3 beta through two signaling pathways. One pathway inhibits insulin-induced GSK-3 beta phosphorylation by blocking insulin activation of Akt. The second pathway stimulates Ser-9 phosphorylation of GSK3 beta, probably via PKC. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Vet Affairs Med Ctr, Res Serv, San Antonio, TX 78284 USA. RP Lin, RZ (reprint author), SUNY Stony Brook, Dept Med, Div Hematol, Stony Brook, NY 11794 USA. RI Lin, Richard/J-1754-2014 OI Lin, Richard/0000-0002-3473-7276 NR 50 TC 49 Z9 50 U1 1 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 NOV 2 PY 2001 VL 276 IS 44 BP 40910 EP 40916 DI 10.1074/jbc.M103480200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488FM UT WOS:000171925600072 PM 11533051 ER PT J AU Osawa, M Tong, KI Lilliehook, C Wasco, W Buxbaum, JD Cheng, HYM Penninger, JM Ikura, M Ames, JB AF Osawa, M Tong, KI Lilliehook, C Wasco, W Buxbaum, JD Cheng, HYM Penninger, JM Ikura, M Ames, JB TI Calcium-regulated DNA binding and oligomerization of the neuronal calcium-sensing protein, calsenilin/DREAM/KChIP3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOVERIN; CALSENILIN; CYCLASE; SENSOR AB Calsenilin/DREAM/KChIP3, a member of the recoverin branch of the EF-hand superfamily, interacts with presenilins, serves as a calcium-regulated transcriptional repressor, and interacts with A-type potassium channels. Here we report physicochemical characterization of calcium binding, oligomerization, and DNA binding of human calsenilin/DREAM/KChIP3. Equilibrium Ca2+ binding measurements indicate that the protein binds 3 Ca2+ with a dissociation constant of 14 muM and a Hill coefficient of 0.7. Dynamic light scattering and size exclusion chromatography show that the Ca2+-bound protein exists as a dimer at protein concentrations lower than 150 muM and forms a tetramer at concentrations above 200 muM. The Ca2+-free protein is a tetramer in the concentration range 20-450 muM. Isothermal titration calorimetry and dynamic light scattering indicate that the Ca2+-free protein tetramer binds endothermically (DeltaH = +25 kcal/mol) to four molecules of DNA derived from the downstream regulatory element (DRE) of either the prodynorphin or c-fos genes. One DRE molecule binds tightly to the protein with a dissociation constant (K-d) of 75 nM, and the other three bind more weakly (K-d = 640 nM). No significant DNA binding was observed for the Ca2+-bound protein. The N-terminal protein fragment (residues 1-70) binds nonspecifically to DRE in a Ca2+-independent manner, whereas a C-terminal fragment containing the four EF-hands (residues 65-256) binds DRE (K-d = 200 nM) in a Ca2+-regulated and sequence-specific fashion. The C-terminal fragment is a tetramer in the Ca2+-free state and dissociates into dimers at saturating Ca2+ levels. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. Univ Toronto, Ontario Canc Inst, Div Mol & Struct Biol, Toronto, ON M5G 2M9, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Neurobiol, New York, NY 10029 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Univ Toronto, Amgen Inst, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada. Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1, Canada. RP Ames, JB (reprint author), Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. RI Penninger, Josef/I-6860-2013; OI Penninger, Josef/0000-0002-8194-3777; Buxbaum, Joseph/0000-0001-8898-8313 FU NEI NIH HHS [EY12347]; NIA NIH HHS [AG05138, AG15801] NR 29 TC 95 Z9 100 U1 0 U2 3 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 NOV 2 PY 2001 VL 276 IS 44 BP 41005 EP 41013 DI 10.1074/jbc.M105842200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488FM UT WOS:000171925600085 PM 11535596 ER PT J AU Shah, K Vervoort, J de Vries, SC AF Shah, K Vervoort, J de Vries, SC TI Role of threonines in the Arabidopsis thaliana somatic embryogenesis receptor kinase 1 activation loop in phosphorylation. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUCINE-RICH REPEATS; PROTEIN-KINASE; SIGNAL-TRANSDUCTION; INSULIN-RECEPTOR; TYROSINE KINASE; CRYSTAL-STRUCTURE; GENE ENCODES; TRANSMEMBRANE; PLANT; EXPRESSION AB The Arabidopsis thaliana somatic embryogenesis receptor kinase 1 (AtSERK1) gene encodes a receptor-like protein kinase that is transiently expressed during embryogenesis. To determine the intrinsic biochemical properties of the AtSERK1 protein, we have expressed the intracellular catalytic domain as a glutathione S-transferase fusion protein in Escherichia coli. The AtSERK1-glutathione S-transferase fusion protein mainly autophosphorylates on threonine residues (K-m for ATP, 4 x 10(-6) M), and the reaction is Mg2+ dependent and inhibited by Mn2+. A K330E substitution in the kinase domain of AtSERK1 abolishes all kinase activity. The active AtSERK1(kin) can phosphorylate inactive AtSERK1(K330E) protein, suggesting an intermolecular mechanism of autophosphorylation. The AtSERK1 kinase protein was modeled using the insulin receptor kinase as a template. On the basis of this model, threonine residues in the AtSERK1 activation loop of catalytic subdomain VIII are potential targets for phosphorylation. AtSERK1 phosphorylation on myelin basic protein and casein showed tyrosine, serine, and threonine as targets, demonstrating that AtSERK1 is a dual specificity kinase. Replacing Thr-468 with either alanine or glutamic acid not only obliterated the ability of the AtSERK1 protein to be phosphorylated but also inhibited phosphorylation on myelin basic protein and casein, suggesting that Thr-468 is essential for AtSERK-mediated signaling. C1 Univ Wageningen & Res Ctr, Mol Biol Lab, NL-6703 HA Wageningen, Netherlands. Univ Wageningen & Res Ctr, Biochem Lab, NL-6703 HA Wageningen, Netherlands. RP Shah, K (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, 149 E 13th St 6204, Charlestown, MA 02129 USA. NR 43 TC 80 Z9 85 U1 0 U2 3 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 NOV 2 PY 2001 VL 276 IS 44 BP 41263 EP 41269 DI 10.1074/jbc.M102381200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488FM UT WOS:000171925600118 PM 11509554 ER PT J AU Rosowsky, A Chen, H AF Rosowsky, A Chen, H TI A novel method of synthesis of 2,4-diamino-6-arylmethylquinazolines using palladium(0)-catalyzed organozinc chemistry SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; TRIMETHOPRIM-SULFAMETHOXAZOLE; ANTIBACTERIAL ACTIVITIES; DIHYDROFOLATE-REDUCTASE; FOLATE ANTAGONISTS; ORGANIC HALIDES; ANTI-TUMOR; TRIMETREXATE; ANTIFOLATE; PIRITREXIM 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. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM andre_rosowsky@dfci.harvard.edu FU NIAID NIH HHS [R01-AI-29904] NR 27 TC 31 Z9 31 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 2 PY 2001 VL 66 IS 22 BP 7522 EP 7526 DI 10.1021/jo010536i PG 5 WC Chemistry, Organic SC Chemistry GA 489CD UT WOS:000171973700042 PM 11681973 ER PT J AU Gordon, JA Billings, J Asplin, BR Rhodes, KV AF Gordon, JA Billings, J Asplin, BR Rhodes, KV TI Safety net research in emergency medicine: Proceedings of the Academic Emergency Medicine Consensus Conference on "The unraveling safety net" SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE safety net; emergency department; research agenda ID CLINICAL PREVENTIVE SERVICES; CARE; HEALTH AB A primary goal of the Academic Emergency Medicine Consensus Conference, "The Unraveling Safety Net: Research Opportunities and Priorities," was to explore a formal research agenda for safety net research in emergency medicine. This paper represents the thoughts of active health services researchers regarding the structure and direction of such work, including some examples from their own research. The current system for safety net care is described, and the emergency department is conceptualized as a window on safety net patients and systems, uniquely positioned to help study and coordinate integrated processes of care. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Emergency Med, Div Emergency Med,Inst Hlth Policy,Partners Healt, Boston, MA 02114 USA. NYU, Robert F Wagner Grad Sch Publ Serv, Ctr Hlth & Publ Serv Res, New York, NY USA. Reg Hosp, HealthPartners Res Fdn, Dept Emergency Med, St Paul, MN USA. Univ Chicago, Sect Emergency Med, Chicago, IL 60637 USA. RP Gordon, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Emergency Med, Div Emergency Med,Inst Hlth Policy,Partners Healt, 55 Fruit St,Clin 115, Boston, MA 02114 USA. NR 26 TC 56 Z9 57 U1 1 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2001 VL 8 IS 11 BP 1024 EP 1029 DI 10.1111/j.1553-2712.2001.tb01110.x PG 6 WC Emergency Medicine SC Emergency Medicine GA 488YQ UT WOS:000171964900005 PM 11691663 ER PT J AU Gordon, JA Dupuie, TA AF Gordon, JA Dupuie, TA TI Child health insurance outreach through the emergency department: A pilot study SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE health insurance; children; emergency departments ID CARE AB In 1997 the U.S. government funded the Children's Health Insurance Program (CHIP), but the $48 billion initiative has had limited success in finding and enrolling uninsured children. While such children are more likely to receive care in emergency departments (EDs), no national initiative has targeted EDs for child health insurance outreach. Objective: As a pilot study for a national multicenter study, this study evaluated the effectiveness of child health insurance outreach in an ED setting. Methods: This was a prospective observational study of the outreach efforts of a single case manager from August 1998 to July 1999, performed at Foote Hospital ED in Jackson, Michigan (45,000 visits/year). All patients less than or equal to 18 years old presenting during the duty-hours of the intervention worker were eligible. The case manager approached the parent of all uninsured children and provided information and an application for government-sponsored health insurance. She followed up with a brief phone interview of each parent to determine whether the targeted child had received the insurance, and whether the new coverage was due to the ED referral. Missing information was confirmed from state insurance records. Data were analyzed with frequency tabulations and 95% confidence intervals. Results: Seventy-eight children participated (median age 7 years; 55% male; 87% white). Forty-four percent (95% CI = 32% to 55%) of families referred for government-sponsored child health insurance successfully obtained it; 31% (95% CI = 21% to 42%) could be traced directly to intervention efforts by interview (n = 17) or by state records (n = 7). Nineteen percent (95% CI = 11% to 30%) got other private insurance. Of those who got government-sponsored insurance due to the intervention, all but one were covered by Medicaid. Conclusions: The ED may be an important outreach site for child health insurance programs. National efforts to address the lack of insurance among children should include partnerships with the ED. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Emergency Med,Partners Healthcare Sys, Dept Emergency Med,Inst Hlth Policy, Boston, MA 02114 USA. Univ Michigan, Hlth Syst, Foote Hosp, Dept Emergency Med, Jackson, MI USA. RP Gordon, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Emergency Med,Partners Healthcare Sys, Dept Emergency Med,Inst Hlth Policy, 55 Fruit St,CLN 115, Boston, MA 02114 USA. NR 10 TC 11 Z9 13 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2001 VL 8 IS 11 BP 1088 EP 1090 DI 10.1111/j.1553-2712.2001.tb01120.x PG 3 WC Emergency Medicine SC Emergency Medicine GA 488YQ UT WOS:000171964900015 PM 11691673 ER PT J AU Campbell, EG Weissman, JS Causino, N Blumenthal, D AF Campbell, EG Weissman, JS Causino, N Blumenthal, D TI Market competition and patient-oriented research: The results of a national survey of medical school faculty SO ACADEMIC MEDICINE LA English DT Article ID MANAGED CARE AB Purpose. To understand the effect of market competition on patient-oriented research at U.S. medical schools and teaching hospitals. Method. From a multi-stage stratified, random sample, the authors surveyed 3,804 research faculty at 117 U.S. medical schools. The questionnaire assessed five variables, the type of research conducted by the respondent, changes in patient-oriented and non-clinical research in the preceding three years, amount of time spent on patient care, market stage of the respondent's institution, and research productivity. Results. Of the 2,336 faculty who responded (62%), 84% of those conducting patient-oriented research and 80% of those engaged in non-clinical research reported conducting the same amount of research or more in 1996-1997 than in the preceding three years. However, both patient-oriented and non-clinical researchers in the most competitive health care markets and those with high levels of patient care duties were most likely to report decreases in the amounts of such research conducted in the previous three years. Further, researchers reporting such decreases had been as productive in recent years and over their careers as had those who did not report a decrease. Conclusions. This study provides additional evidence of the negative relationships that exist between high levels of market competition and patient care services on the patient-oriented and non-clinical research missions of teaching hospitals. C1 Massachusetts Gen Hosp, Inst Hlth Care Policy, Boston, MA 02114 USA. Partners Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Campbell, EG (reprint author), Inst Hlth Care Policy, 50 Stanford St,9th Floor, Boston, MA 02114 USA. NR 17 TC 4 Z9 4 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 2001 VL 76 IS 11 BP 1119 EP 1126 DI 10.1097/00001888-200111000-00016 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 492GG UT WOS:000172159600013 PM 11704515 ER PT J AU Loeffler, S Seed, B Campbell, IL Weis, J Weissenberger, J AF Loeffler, S Seed, B Campbell, IL Weis, J Weissenberger, J TI IL-6 induces VEGF promoter activity in vivo SO ACTA NEUROPATHOLOGICA LA English DT Meeting Abstract C1 Univ Bern, Div Neuropathol, CH-3012 Bern, Switzerland. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 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 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD NOV PY 2001 VL 102 IS 5 BP 533 EP 533 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 483XY UT WOS:000171662200086 ER PT J AU Srivastava, R Landrigan, C Gidwani, P Harary, OH Muret-Wagstaff, S Homer, CJ AF Srivastava, R Landrigan, C Gidwani, P Harary, OH Muret-Wagstaff, S Homer, CJ TI Pediatric hospitalists in Canada and the United States: A survey of pediatric academic department chairs SO AMBULATORY PEDIATRICS LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Ambulatory-Pediatric-Association CY MAY 01-04, 1999 CL SAN FRANCISCO, CALIFORNIA SP Ambulatory Pediat Assoc DE academic medical center; hospitalist; pediatric health services delivery ID SERVICE; IMPACT; CARE AB Objectives.-To document the prevalence and practice patterns of pediatric hospitalists in academic centers in Canada and the United States to characterize academic pediatric department chairs' definition of the term hospitalist;, and to characterize pediatric department chairs' views of the training requirements for pediatric hospitalists. Methods.-A 14-item questionnaire was sent to all 145 pediatric department chairs from Canada and the United States during the fall of 1998. We defined hospitalists as physicians spending at least 25% of their time in inpatient care. Results.-Of the 145 eligible pediatric chairs, 128 (89%) responded (United States, 111/126: Canada. 14/16: Puerto Rico, 3/3). Ninety-nine (77%) of 128 pediatric chairs either have (64/128) or are planning to have (35/128) hospitalists in their institutions. Within academic programs with hospitalists, 82% of hospitalists currently work on general pediatric wards. Two thirds of hospitalists teach. 50% provide outpatient care, 50% have administrative duties. and 44% conduct research. One hundred eight (84%) of 128 believe that hospitalists should spend at least 50% of their time in inpatient care. Less than one third (30%) of pediatric chairs believe that hospitalists require training not currently provided in residency. Conclusions.-A large proportion of academic pediatric centers either employed or planned to employ hospitalists in 1998. Pediatric academic department chairs do not see a need for training beyond residency for hospitalists. Further studies should address how pediatric hospitalists affect quality of care, cost, and patient satisfaction. C1 Harvard Univ, Pediat Hlth Serv Res Fellowship Program, Childrens Hosp, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, MassGen Hosp Children, Boston, MA USA. RP Srivastava, R (reprint author), Univ Utah, Div Gen Pediat, Primary Childrens Med Ctr, 100 N Med Dr, Salt Lake City, UT 84113 USA. FU BHP HRSA HHS [T32 PE10018] NR 9 TC 21 Z9 21 U1 1 U2 1 PU AMBULATORY PEDIATRIC ASSOC PI MCLEAN PA 6728 OLD MCLEAN VILLAGE DR, MCLEAN, VA 22101-3906 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD NOV-DEC PY 2001 VL 1 IS 6 BP 338 EP 339 DI 10.1367/1539-4409(2001)001<0338:PHICAT>2.0.CO;2 PG 2 WC Pediatrics SC Pediatrics GA 495VZ UT WOS:000172362200009 PM 11888425 ER PT J AU Mukamal, KJ Maclure, M Sherwood, JB Kannam, JP Muller, JE Mittleman, MA AF Mukamal, KJ Maclure, M Sherwood, JB Kannam, JP Muller, JE Mittleman, MA TI Height is not associated with long-term survival after acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID CARDIOVASCULAR-DISEASE; SHORT STATURE; MORTALITY; WOMEN; WEIGHT; RISK; EVENTS AB Background Studies show an inverse association between height and risk of myocardial infarction. How height affects survival after acute myocardial infarction is uncertain. Methods In the Determinants of Myocardial Infarction Onset Study, trained interviewers performed chart reviews and face-to-face interviews with 1935 patients hospitalized with acute myocardial infarction in 45 US medical centers between 1989 and 1993. We excluded 15 patients with missing information on height. After a search of the National Death Index for patients who died before 1996, we analyzed the relationship of height and survival with Cox proportional hazards regression. Results Of the 1920 eligible patients, 317 (17%) died during a median follow-up of 3.8 years. Height was positively associated with younger age, greater educational attainment, and a lower likelihood of being sedentary among both men and women. Height was not associated with long-term survival among women in unadjusted or adjusted analyses. Among men, height was associated with survival only in unadjusted analyses; adjustment for age eliminated this association. We found no relationship between height and survival in any individual age group among men or women. Conclusions Although stature may be associated with the risk of acute myocardial infarction, it is not associated with long-term survival after such an event. C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave,LY-303, Boston, MA 02215 USA. FU NHLBI NIH HHS [R01HL41016]; NIAAA NIH HHS [K23AA00299] NR 15 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2001 VL 142 IS 5 BP 852 EP 856 DI 10.1067/mhj.2001.119131 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 491JE UT WOS:000172104600018 PM 11685174 ER PT J AU Kloner, RA Das, S Poole, WK Perrit, R Muller, J Cannon, CP Braunwald, E AF Kloner, RA Das, S Poole, WK Perrit, R Muller, J Cannon, CP Braunwald, E TI Seasonal variation of myocardial infarct size SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB Whether the size of myocardial infarction is constant through the different seasons of the year is unknown. In this analysis of enzyme-based myocardial infarct size from the MILIS study, which was a prethrombolytic era study, and the TIMI-4 study, which was a thrombolytic-based study, myocardial infarct size based on creatine kinase-MB analysis was smaller during the summer, compared with the rest of the year. Myocardial infarct size may vary by season. C1 Hosp Good Samaritan, Inst Heart, Los Angeles, CA 90017 USA. Univ So Calif, Los Angeles, CA USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Kloner, RA (reprint author), Hosp Good Samaritan, Inst Heart, 1225 Wilshire Blvd, Los Angeles, CA 90017 USA. RI Kloner, Robert/B-2971-2012 NR 9 TC 26 Z9 26 U1 0 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2001 VL 88 IS 9 BP 1021 EP + DI 10.1016/S0002-9149(01)01981-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 488YG UT WOS:000171964100016 PM 11704000 ER PT J AU Harper, RJ Brady, WJ Perron, AD Mangrum, M AF Harper, RJ Brady, WJ Perron, AD Mangrum, M TI The paced electrocardiogram: Issues for the emergency physician SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE ECG; pacemaker; electrocardiogram ID ACUTE MYOCARDIAL-INFARCTION; DIAGNOSIS; PACEMAKER; RHYTHMS AB Since the first introduction of implantable pacemaker approximately 50 years ago, these devices have become increasingly more common and more complex. It is estimated that there are approximately 1 million patients with implanted pacemakers in the United States and I with an aging population, the number of pacemakers is certain to increase. This review focuses on basics of pacemaker function as well as the common rhythm disturbance issues and other clinical syndromes that the emergency physician is likely to encounter. Copyright (C) 2001 by W.B. Saunders Company. C1 Univ Virginia, Hlth Sci Ctr, Dept Emergency Med, Charlottesville, VA 22908 USA. Oregon Hlth Sci Univ, Dept Emergency Med, Portland VA Med Ctr, Portland, OR 97201 USA. Univ Virginia, Hlth Sci Ctr, Dept Internal Med, Div Cardiol Electrophysiol, Charlottesville, VA 22908 USA. RP Brady, WJ (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Emergency Med, Box 523-21, Charlottesville, VA 22908 USA. NR 13 TC 3 Z9 3 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2001 VL 19 IS 7 BP 551 EP 560 DI 10.1053/ajem.2001.24486 PG 10 WC Emergency Medicine SC Emergency Medicine GA 491LC UT WOS:000172109000005 PM 11699000 ER PT J AU Bauer, KA AF Bauer, KA TI Fondaparinux sodium: A selective inhibitor of factor Xa SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article; Proceedings Paper CT ASHP Midyear Clinical Meeting CY DEC 05-07, 2000 CL LAS VEGAS, NEVADA SP ASHP DE anticoagulants; duration of action; mechanism of action; Org-31540; pharmacokinetics; SR-90107A; thromboembolism; toxicity ID SYNTHETIC PENTASACCHARIDE; ANTITHROMBIN-III; HIGH-AFFINITY; HEPARIN; THROMBIN; THROMBOCYTOPENIA; GENERATION; ABSENCE AB The pharmacology and mechanism of action of fondaparinux sodium are described. Fondaparinux sodium is the first agent of a new class of anticoagulants that selectively target factor Xa. It has a linear, dose-dependent pharmacokinetic profile, which provides a highly predictable response. It is 100% bioavailable, has a rapid onset of action, and has a half-life of 14 to 16 hours, allowing for sustained antithrombotic activity over a 24-hour period. The drug does not affect prothrombin time or activated partial thromboplastin time, nor does it affect platelet function or aggregation. Studies in patients with confirmed heparin-induced thrombocytopenia demonstrate that the drug is not associated with in vitro cross-reactivity to heparin antibodies. Fondaparinux sodium appears to meet the criteria for an ideal antithrombotic agent: equal or better effectiveness than currently available agents, a low bleeding risk, no need for laboratory monitoring, and once-daily administration. C1 VA Boston Healthcare Syst, Hematol Sect, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Bauer, KA (reprint author), VA Boston Healthcare Syst, Hematol Sect, 330 Brookline Ave, Boston, MA 02215 USA. NR 15 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD NOV 1 PY 2001 VL 58 IS 21 SU 2 BP S14 EP S17 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 491TV UT WOS:000172125900003 PM 11715834 ER PT J AU Andress, DL AF Andress, DL TI Intravenous versus oral vitamin D therapy in dialysis patients: What is the question? SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE vitamin D therapy; intravenous (IV); oral; hypercalcemia; hyperphosphatemia ID CHRONIC-HEMODIALYSIS PATIENTS; CHRONIC-RENAL-FAILURE; SECONDARY HYPERPARATHYROIDISM; PARATHYROID-HORMONE; CALCITRIOL THERAPY; SERUM PHOSPHORUS; 1,25-DIHYDROXYCHOLECALCIFEROL; SUPPRESSION; DISEASE AB The debate regarding the administration of vitamin D (parenteral versus pulse oral) in dialysis patients has centered on the efficacy of parathyroid hormone (PTH) suppression while ignoring other questions related to complications and compliance. Past studies looking at efficacy showed no differences during short-term treatment, although the small number of patients studied reduces the significance of these findings. Long-term studies with larger populations have shown that parenteral calcitriol is more effective than pulse oral calcitriol in suppressing PTH. When considering the questions of complications and compliance the current literature demonstrates that parenteral vitamin D therapy is associated with fewer episodes of hypercalcemia and hyperphosphatemia and that patients receiving pulse oral calcitriol require more phosphate binders. Because of the documented high noncompliance rate with oral medications in the dialysis population, parenterally administered vitamin D is expected to more completely suppress PTH long term and result in fewer parathyroidectomies. Based on these considerations it is suggested that parenteral vitamin D analogs are superior to pulse oral calcitriol for the long-term control of hyperparathyroidism in dialysis patients. (C) 2001 by the National Kidney Foundation, Inc. C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Andress, DL (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 24 TC 12 Z9 12 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2001 VL 38 IS 5 SU 5 BP S41 EP S44 DI 10.1053/ajkd.2001.28108 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 489BW UT WOS:000171973000005 PM 11689386 ER PT J AU Yonetsu, K Bianchi, JG Troulis, MJ Curtin, HD AF Yonetsu, K Bianchi, JG Troulis, MJ Curtin, HD TI Unusual CT appearance in an odontogenic keratocyst of the mandible: Case report SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID LESIONS AB An expansile lesion in the body of the left mandible had high attenuation (225 HU) on nonenhanced CT scans. Histologic examination revealed an odontogenic keratocyst with no evidence of mineralization or calcification within the lesion. The high attenuation was considered to be due to highly concentrated protein of thick, viscous keratin in the lumen of the keratocyst. C1 Nagasaki Univ, Hosp Dent, Dept Radiol, Nagasaki, Japan. Harvard Univ, Sch Dent Med, Dept Maxillofacial Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Curtin, HD (reprint author), 243 Charles St, Boston, MA 02114 USA. NR 13 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 2001 VL 22 IS 10 BP 1887 EP 1889 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 532JV UT WOS:000174472100017 PM 11733321 ER PT J AU Aiello, LP Cahill, MT Wong, JS AF Aiello, LP Cahill, MT Wong, JS TI Systemic considerations in the management of diabetic retinopathy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; URINARY ALBUMIN EXCRETION; EURODIAB IDDM COMPLICATIONS; INSULIN-DEPENDENT DIABETICS; ENDOTHELIAL GROWTH-FACTOR; SYSTOLIC BLOOD-PRESSURE; AGED 15-50 YEARS; RISK-FACTORS; MACULAR EDEMA; PROLIFERATIVE RETINOPATHY AB PURPOSE: To highlight the systemic factors which affect onset and/or progression of diabetic retinopathy (DR) and to emphasize the role and responsibilities of ophthalmologists and other eye care providers to ensure that appropriate systemic medical evaluation of the patient with diabetes is being pursued. DESIGN: Literature review of publications relevant to diabetic retinopathy, blood glucose control, diabetes meld litus type, hypertension, renal disease, elevated serum lipids, exercise, pregnancy, anticoagulation, thrombolysis, smoking, anemia and antioxidant ingestion. FINDINGS: Intensive blood glucose control and control of systemic hypertension reduce the risk of new onset DR and slow the progression of existing DR. Severe DR may be an indicator of renal disease while severe renal disease and its treatment can affect the progression of DR. Elevated serum lipids are associated with macular exudate and moderate visual loss. Certain types of excessive exercise in patients with advanced stages of retinopathy may aggravate vitreous hemorrhage. During pregnancy, DR should be monitored closely as transient progression of DR can occur. Therapeutic anticoagulation and thrombolysis are not contraindicated at any stage of DR. Anemia can result in progression of DR, smoking in general should be discouraged, and the role of antioxidant therapy requires further study. CONCLUSIONS: Blindness from diabetic retinopathy is now largely preventable with timely detection and appropriate interventional therapy. Routine, repetitive, lifelong, expert clinical retinal examination is essential for the fundamental ophthalmic care of the patient with diabetes. However, diabetes mellitus is a systemic disease and thus optimal ophthalmic care must include diligent evaluation and treatment of concomitant systemic disorders that influence the development, progression and ultimate outcome of diabetic retinopathy. Optimization of these systemic considerations through an intensive, multi disciplinary, healthcare team,based approach will maximize the ophthalmic and general health of these patients. Ophthalmologists and other eye care providers are critical members of this team with unique responsibilities to ensure that appropriate systemic medical evaluation is being pursued. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM LPAiello@joslin.harvard.edu NR 199 TC 80 Z9 88 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 EI 1879-1891 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2001 VL 132 IS 5 BP 760 EP 776 DI 10.1016/S0002-9394(01)01124-2 PG 17 WC Ophthalmology SC Ophthalmology GA 487PP UT WOS:000171884700019 PM 11704039 ER PT J AU Pettit, AR Ji, H von Stechow, D Muller, R Goldring, SR Choi, YW Benoist, C Gravallese, EM AF Pettit, AR Ji, H von Stechow, D Muller, R Goldring, SR Choi, YW Benoist, C Gravallese, EM TI TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID OSTEOCLAST DIFFERENTIATION FACTOR; FACTOR FAMILY MEMBER; COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; OSTEOPROTEGERIN LIGAND; MARROW CULTURES; T-CELL; NONDESTRUCTIVE EVALUATION; COMPUTED TOMOGRAPHY; INHIBITORY FACTOR AB There is considerable evidence that osteoclasts are involved in the pathogenesis of focal bone erosion in rheumatoid arthritis. Tumor necrosis factor-related activation-induced cytokine, also known as receptor activator of nuclear factor-kappa beta ligand (TRANCE/ RANKL) is an essential factor for osteoclast differentiation. In addition to its role in osteoclast differentiation and activation, TRANCE/RANKL also functions to augment T-cell dendritic cell cooperative interactions. To further evaluate the role of osteoclasts in focal bone erosion in arthritis, we generated inflammatory arthritis in the TRANCE/RANKL knockout mouse using a serum transfer model that bypasses the requirement for T-cell activation. These animals exhibit an osteopetrotic phenotype characterized by the absence of osteoclasts. Inflammation, measured by clinical signs of arthritis and histopathological scoring, was comparable in wild-type and TRANCE/ RANKL knockout mice. Microcomputed tomography and histopathological analysis demonstrated that the degree of bone erosion in TRANCE/RANKL knockout mice was dramatically reduced compared to that seen in control littermate mice. in contrast, cartilage erosion was present in both control littermate and TRANCE/RANKL knockout mice. These results confirm the central role of osteoclasts in the pathogenesis of bone erosion in arthritis and demonstrate distinct mechanisms of cartilage destruction and bone erosion in this animal model of arthritis. C1 Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, New England Baptist Bone & Joint Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. Harvard Univ, Sch Med, Orthopaed Biomech Lab, Beth Israel Deaconess Med Ctr, Boston, MA USA. ETH Zurich, Inst Biomed Engn, Zurich, Switzerland. Univ Zurich, Zurich, Switzerland. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Gravallese, EM (reprint author), Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, New England Baptist Bone & Joint Inst, 4 Blackfan Circle, Boston, MA 02115 USA. RI Muller, Ralph/A-1198-2008; Pettit, Allison/G-2591-2010 OI Muller, Ralph/0000-0002-5811-7725; Pettit, Allison/0000-0003-4707-7892 FU NIDDK NIH HHS [R01 DK046773, R01-DK46773] NR 50 TC 387 Z9 403 U1 1 U2 10 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2001 VL 159 IS 5 BP 1689 EP 1699 DI 10.1016/S0002-9440(10)63016-7 PG 11 WC Pathology SC Pathology GA 489JJ UT WOS:000171988000012 PM 11696430 ER PT J AU Assil, IQ Abou-Samra, AB AF Assil, IQ Abou-Samra, AB TI N-glycosylation of CRF receptor type 1 is important for its ligand-specific interaction SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE corticotropin-releasing factor receptors; tunicamycin ID CORTICOTROPIN-RELEASING-FACTOR; CELL-SURFACE EXPRESSION; UROTENSIN-I; FUNCTIONAL EXPRESSION; ENDOPLASMIC-RETICULUM; LINKED GLYCOSYLATION; MOLECULAR-CLONING; HUMAN UROCORTIN; BINDING; NEUROPEPTIDE AB The corticotropin-releasing factor (CRF) receptor type 1 (CRFR1) contains five potential N-glycosylation sites: N38, N45, N78, N90, and N98. Cells expressing CRFR1 were treated with tunicamycin to block receptor glycosylation. The nonglycosylated receptor did not bind the radioligand and had a decreased cAMP stimulation potency in response to CRF. To determine which of the polysaccharide chain(s) is/are involved in ligand interaction, the polysaccharide chains were deleted using site-directed mutagenesis of the glycosylation consensus, N-X-S/T. Two sets of mutations were performed for each glycosylation site: N to Q and S/T to A, respectively. The single mutants Q38, Q45, Q78, Q90, Q98, A40, A47, A80, A92, and A100 and the double mutants A40/A47 and A80/A100 were well expressed, bound CRF, sauvagine (SVG), and urotensin-I (UTS-I) with a normal affinity, and increased cAMP accumulation with a high efficiency. In contrast, the combined mutations A80/A92/A100, A40/A80/A92/A100, and A40/A47/A80/A92/A100 had low levels of expression, did not bind the radioligand, and had a decreased cAMP stimulation. These data indicate the requirement for three or more polysaccharide chains for normal CRFR1 function. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abou-Samra, AB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02113 USA. FU NIDDK NIH HHS [2R01 DK 45020] NR 37 TC 22 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2001 VL 281 IS 5 BP E1015 EP E1021 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 484MM UT WOS:000171694200017 PM 11595658 ER PT J AU Kresse, AE Million, M Saperas, E Tache, Y AF Kresse, AE Million, M Saperas, E Tache, Y TI Colitis induces CRF expression in hypothalamic magnocellular neurons and blunts CRF gene response to stress in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE 2,4,6-trinitrobenzenesulfonic acid; arginine vasopressin gene expression; supraoptic nucleus; osmolarity; heteronuclear corticotropin-releasing factor gene expression; defecation; food intake ID CORTICOTROPIN-RELEASING HORMONE; PARVOCELLULAR NEUROSECRETORY NEURONS; ADJUVANT-INDUCED ARTHRITIS; WATER-AVOIDANCE STRESS; PARAVENTRICULAR NUCLEUS; DIFFERENTIAL REGULATION; ARGININE-VASOPRESSIN; NEUROPEPTIDE GENES; FOS EXPRESSION; LEWIS RATS AB We investigated hypothalamic neuronal corticotropin-releasing factor (CRF) gene expression changes in response to visceral inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNB) and acute stress. Seven days after TNB, rats were subjected to water-avoidance stress (WAS) or restraint for 30 min and euthanized. Hypothalamic CRF primary transcripts (heteronuclear RNA, hnRNA) and CRF and arginine vasopressin (AVP) mRNAs were assessed by in situ hybridization. Antisense S-35-labeled cRNA probes against CRF mRNA intronic and exonic sequences and an oligonucleotide probe against the AVP mRNA were used. TNB induced macroscopic lesions and a fivefold elevation in myeloperoxidase activity in the colon. Colitis increased CRF hnRNA and mRNA signals in the magnocellular part of the paraventricular nucleus of the hypothalamus (PVN) and supraoptic neurons, whereas AVP mRNA was not altered. Colitis did not modify CRF hnRNA signal in the parvocellular part of the PVN (pPVN), plasma corticosterone, and serum osmolarity levels. However, CRF hnRNA expression in the pPVN and the rise in corticosterone and defecation induced by WAS or restraint were blunted in colitic rats. These data show that colitis upregulates CRF gene synthesis in magnocellular hypothalamic neurons but dampens CRF gene transcription in the pPVN and plasma corticosterone responses to environmental acute stressors. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, CURE, Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90073 USA. Autonomous Univ Barcelona, Hosp Gen Valle Hebron, Digest Syst Res Unit, E-08035 Barcelona, Spain. RP Million, M (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, CURE, Dept Med,Digest Dis Div, Bldg 115,Rm 203,11302 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-33061, DK-41301] NR 58 TC 40 Z9 40 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 2001 VL 281 IS 5 BP G1203 EP G1213 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 483RB UT WOS:000171648700012 PM 11668029 ER PT J AU Sarkar, S Hobson, AR Furlong, PL Woolf, CJ Thompson, DG Aziz, Q AF Sarkar, S Hobson, AR Furlong, PL Woolf, CJ Thompson, DG Aziz, Q TI Central neural mechanisms mediating human visceral hypersensitivity SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE esophagus; pain; acid; dorsal horn neurones ID SOMATOSENSORY EVOKED-POTENTIALS; SECONDARY HYPERALGESIA; ELECTRICAL-STIMULATION; INTRADERMAL INJECTION; PAIN HYPERSENSITIVITY; OPTIMAL PARAMETERS; ESOPHAGUS; INFLAMMATION; SENSATION; RESPONSES AB Although visceral hypersensitivity is thought to be important in generating symptoms in functional gastrointestinal disorders, the neural mechanisms involved are poorly understood. We recently showed that central sensitization (hyperexcitability of spinal cord sensory neurones) may play an important role. In this study, we demonstrate that after a 30-min infusion of 0.15 M HCl acid into the healthy human distal esophagus, we see a reduction in the pain threshold to electrical stimulation of the non-acid-exposed proximal esophagus (9.6 +/- 2.4 mA) and a concurrent reduction in the latency of the N1 and P2 components of the esophageal evoked potentials (EEP) from this region (10.4 +/- 2.3 and 15.8 +/- 5.3 ms, respectively). This reduced EEP latency indicates a central increase in afferent pathway velocity and therefore suggests that hyperexcitability within the central visceral pain pathway contributes to the hypersensitivity within the proximal, non-acid-exposed esophagus (secondary hyperalgesia/allodynia). These findings provide the first electrophysiological evidence that central sensitization contributes to human visceral hypersensitivity. C1 Univ Manchester, Hope Hosp, Sect Gastrointestinal Sci, Salford M6 8HD, Lancs, England. Aston Univ, Neurosci Res Inst, Birmingham B4 7ET, W Midlands, England. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MRC, London W1N 4AL, England. RP Aziz, Q (reprint author), Univ Manchester, Hope Hosp, Sect Gastrointestinal Sci, Clin Sci Bldg, Salford M6 8HD, Lancs, England. NR 50 TC 117 Z9 123 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 2001 VL 281 IS 5 BP G1196 EP G1202 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 483RB UT WOS:000171648700011 PM 11668028 ER PT J AU Zhang, XQ Song, JL Rothblum, LI Lun, MY Wang, XJ Ding, F Dunn, J Lytton, J McDermott, PJ Cheung, JY AF Zhang, XQ Song, JL Rothblum, LI Lun, MY Wang, XJ Ding, F Dunn, J Lytton, J McDermott, PJ Cheung, JY TI Overexpression of Na+/Ca2+ exchanger alters contractility and SR Ca2+ content in adult rat myocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE excitation-contraction coupling; fura 2; cardiac myocyte culture; video imaging ID VENTRICULAR MYOCYTES; CARDIAC MYOCYTES; POSTINFARCTION MYOCYTES; NA+-CA2+ EXCHANGER; PRIMARY CULTURE; CALCIUM; RABBIT; CELLS; HOMEOSTASIS; RELAXATION AB The functional consequences of overexpression of rat heart Na+/Ca2+ exchanger (NCX1) were investigated in adult rat myocytes in primary culture. When maintained under continued electrical field stimulation conditions, cultured adult rat myocytes retained normal contractile function compared with freshly isolated myocytes for at least 48 h. Infection of myocytes by adenovirus expressing green fluorescent protein (GFP) resulted in 95% infection as ascertained by GFP fluorescence, but contraction amplitude at 6-, 24-, and 48- h postinfection was not affected. When they were examined 48 h after infection, myocytes infected by adenovirus expressing both GFP and NCX1 had similar cell sizes but exhibited significantly altered contraction amplitudes and intracellular Ca2+ concentration ([Ca2+](i)) transients, and lower resting and diastolic [Ca2+](i) when compared with myocytes infected by the adenovirus expressing GFP alone. The effects of NCX1 overexpression on sarcoplasmic reticulum (SR) Ca2+ content depended on extracellular Ca2+ concentration ([ Ca2+](o)), with a decrease at low [Ca2+](o) and an increase at high [Ca2+](o). The half-times for [Ca2+](i) transient decline were similar, suggesting little to no changes in SR Ca2+-ATPase activity. Western blots demonstrated a significant (P less than or equal to0.02) threefold increase in NCX1 but no changes in SR Ca2+-ATPase and calsequestrin abundance in myocytes 48 h after infection by adenovirus expressing both GFP and NCX1 compared with those infected by adenovirus expressing GFP alone. We conclude that overexpression of NCX1 in adult rat myocytes incubated at high [Ca2+](o) resulted in enhanced Ca2+ influx via reverse NCX1 function, as evidenced by greater SR Ca2+ content, larger twitch, and [Ca2+](i) transient amplitudes. Forward NCX1 function was also increased, as indicated by lower resting and diastolic [Ca2+](i). C1 Geisinger Med Ctr, Weis Ctr Res, Danville, PA 17822 USA. Univ Calgary, Hlth Sci Ctr, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. RP Cheung, JY (reprint author), Geisinger Med Ctr, Weis Ctr Res, Danville, PA 17822 USA. FU NHLBI NIH HHS [HL-58672]; NIDDK NIH HHS [DK-46678]; NIGMS NIH HHS [GM-46991] NR 33 TC 48 Z9 48 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2001 VL 281 IS 5 BP H2079 EP H2088 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 483TW UT WOS:000171652800027 PM 11668069 ER PT J AU Black, SM Sanchez, LS Mata-Greenwood, E Bekker, JM Steinhorn, RH Fineman, JR AF Black, SM Sanchez, LS Mata-Greenwood, E Bekker, JM Steinhorn, RH Fineman, JR TI sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE phosphodiesterase type 5; soluble guanylate cyclase; circulation ID NITRIC-OXIDE SYNTHASE; VASCULAR ENDOTHELIAL-CELLS; GENE-EXPRESSION; FETAL LAMBS; VASORELAXATION; RELAXATION; MANAGEMENT; ARTERY; LUNGS AB Utilizing aortopulmonary vascular graft placement, we established a lamb model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. We previously demonstrated that endothelial nitric oxide synthase (eNOS) is increased in lambs at age 4 wk. However, these lambs display a selective impairment of endothelium-dependent pulmonary vasodilation that is suggestive of a derangement downstream of NO release. Thus our objective was to characterize potential alterations in the expression and activity of soluble guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5) induced by increased pulmonary blood flow and pulmonary hypertension. Late-gestational fetal lambs (n = 10) underwent in utero placement of an aortopulmonary vascular graft (shunt). Western blotting analysis on lung tissue from 4-wk-old shunted lambs and age-matched controls showed that protein for both subunits of sGC was increased in shunted lamb lungs compared with age-matched controls. Similarly, cGMP levels were increased in shunted lamb lungs compared with age-matched controls. However, PDE5 expression and activity were also increased in shunted lambs. Thus although cGMP generation was increased, concomitant upregulation of PDE5 expression and activity may have (at least partially) limited and accounted for the impairment of endothelium-dependent pulmonary vasodilation in shunted lambs. C1 Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Mol Pharmacol, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Black, SM (reprint author), Northwestern Univ, Sch Med, Dept Pediat, Ward 12-191,303 E Chicago Ave, Chicago, IL 60611 USA. RI Steinhorn, Robin/A-4248-2010 FU NHLBI NIH HHS [HL-61284, R01 HL054705, HL-54705]; NICHD NIH HHS [HD-398110, HD60190] NR 29 TC 53 Z9 55 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 2001 VL 281 IS 5 BP L1051 EP L1057 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 481CQ UT WOS:000171502700003 PM 11597895 ER PT J AU Nakamura, H Luster, AD Tateno, H Jedrzkiewicz, S Tamura, G Haley, KJ Garcia-Zepeda, EA Yamaguchi, K Lilly, CM AF Nakamura, H Luster, AD Tateno, H Jedrzkiewicz, S Tamura, G Haley, KJ Garcia-Zepeda, EA Yamaguchi, K Lilly, CM TI IL-4 differentially regulates eotaxin and MCP-4 in lung epithelium and circulating mononuclear cells SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE interferon-gamma; interleukin-8; A549 cells; BEAS-2B cells; peripheral blood mononuclear cells; interleukin-4; monocyte chemoattractant protein-4 ID MONOCYTE CHEMOATTRACTANT PROTEIN; INTERLEUKIN-8 GENE-EXPRESSION; COLONY-STIMULATING FACTOR; NF-KAPPA-B; BRONCHOALVEOLAR LAVAGE; CC-CHEMOKINE; ALLERGIC INFLAMMATION; EOSINOPHIL RECRUITMENT; BRONCHIAL-ASTHMA; MILD ASTHMA AB To investigate the mechanisms of eosinophil recruitment in allergic airway inflammation, we examined the effects of interleukin (IL)-4, a Th2-type cytokine, on eotaxin and monocyte chemoattractant protein-4 (MCP-4) expression in human peripheral blood mononuclear cells (PBMCs; n = 10), in human lower airway mononuclear cells (n = 5), in the human lung epithelial cell lines A549 and BEAS-2B, and in human cultured airway epithelial cells. IL-4 inhibited eotaxin and MCP-4 mRNA expression induced by IL-1 beta and tumor necrosis factor-alpha in PBMCs but did not significantly inhibit expression in epithelial cells. Eotaxin and MCP-4 mRNA expression was not significantly induced by proinflammatory cytokines in lower airway mononuclear cells. IL-1 beta -induced eotaxin and MCP-4 protein production was also inhibited by IL-4 in PBMCs, whereas IL-4 enhanced eotaxin protein production in A549 cells. In contrast, dexamethasone inhibited eotaxin and MCP-4 expression in both PBMCs and epithelial cells. The divergent effects of IL-4 on eotaxin and MCP-4 expression between PBMCs and epithelial cells may create chemokine concentration gradients between the subepithelial layer and the capillary spaces that may promote the recruitment of eosinophils to the airway in Th2-type responses. C1 Brigham & Womens Hosp, Dept Med, Div Resp, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Keio Univ, Sch Med, Dept Med, Tokyo 160, Japan. RP Lilly, CM (reprint author), Brigham & Womens Hosp, Dept Med, Div Resp, Combined Program Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-03283, HL-64104]; NIAID NIH HHS [AI-40618] NR 70 TC 16 Z9 16 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 2001 VL 281 IS 5 BP L1288 EP L1302 PG 15 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 481CQ UT WOS:000171502700030 PM 11597922 ER PT J AU Evans, SB Wilkinson, CW Bentson, K Gronbeck, P Zavosh, A Figlewicz, DP AF Evans, SB Wilkinson, CW Bentson, K Gronbeck, P Zavosh, A Figlewicz, DP TI PVN activation is suppressed by repeated hypoglycemia but not antecedent corticosterone in the rat SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE paraventricular nucleus; stress; c-Fos; hypoglycemia-associated autonomic failure ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; NEONATAL MONOSODIUM GLUTAMATE; STRESS-INDUCED EXPRESSION; SYMPATHETIC PREGANGLIONIC NEURONS; PITUITARY-ADRENOCORTICAL AXIS; CENTRAL-NERVOUS-SYSTEM; EARLY GENE-EXPRESSION; IMMEDIATE-EARLY GENES; FOS MESSENGER-RNA; VENTROMEDIAL HYPOTHALAMUS AB The mechanism(s) underlying hypoglycemia-associated autonomic failure (HAAF) are unknown. To test the hypothesis that the activation of brain regions involved in the counterregulatory response to hypoglycemia is blunted with HAAF, rats were studied in a 2-day protocol. Neuroendocrine responses and brain activation (c-Fos immunoreactivity) were measured during day 2 insulin-induced hypoglycemia (0.5 U insulin . 100 g body wt(-1) . h(-1) iv for 2 h) after day 1 hypoglycemia (Hypo-Hypo) or vehicle. Hypo-Hypo animals demonstrated HAAF with blunted epinephrine, glucagon, and corticosterone (Cort) responses and decreased activation of the medial hypothalamus [the paraventricular (PVN), dorsomedial (DMH), and arcuate (Arc) nuclei]. To evaluate whether increases in day 1 Cort were responsible for the decreased hypothalamic activation, Cort was infused intracerebroventricularly (72 mug) on day 1 and the response to day 2 hypoglycemia was measured. Intracerebroventricular Cort infusion failed to alter the neuroendocrine response to day 2 hypoglycemia, despite elevating both central nervous system and peripheral Cort levels. However, day 1 Cort blunted responses in two of the same hypothalamic regions as Hypo-Hypo (the DMH and Arc) but not in the PVN. These results suggest that decreased activation of the PVN may be important in the development of HAAF and that antecedent exposure to elevated levels of Cort is not always sufficient to produce HAAF. C1 Dept Vet Affairs, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Evans, SB (reprint author), Dept Vet Affairs, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 63 TC 51 Z9 51 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD NOV PY 2001 VL 281 IS 5 BP R1426 EP R1436 PG 11 WC Physiology SC Physiology GA 483HW UT WOS:000171630200013 PM 11641112 ER PT J AU Wang, LX Martinez, V Rivier, JE Tache, Y AF Wang, LX Martinez, V Rivier, JE Tache, Y TI Peripheral urocortin inhibits gastric emptying and food intake in mice: differential role of CRF receptor 2 SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE antisauvagine-30; astressin B; capsaicin; cholecystokinin; CP-154,526; DMP904; corticotropin-releasing factor ID CORTICOTROPIN-RELEASING FACTOR; FACTOR ANTAGONISTS; ASTRESSIN ANALOGS; NERVOUS-SYSTEM; LEAN MICE; RAT-BRAIN; CHOLECYSTOKININ; EXPRESSION; MODULATION; SAUVAGINE AB Intraperitoneal urocortin inhibits gastric emptying and food intake in mice. We investigated corticotropin-releasing factor receptor (CRF-R) subtypes involved in intraperitoneal urocortin actions using selective CRF-R antagonists. Gastric emptying was measured 2 h after a chow meal, and food intake was measured hourly after an 18-h fast in mice. Urocortin (3 mug/kg ip) inhibited gastric emptying by 88%. The CRF-R1/CRF-R2 antagonist astressin B (30 mug/kg ip) and the selective CRF-R2 antagonist antisauvagine-30 (100 mug/kg ip) completely antagonized urocortin action, whereas the selective CRF-R1 antagonist CP-154,526 (10 mg/kg ip) had no effect. Urocortin (1-10 mug/kg ip) dose dependently decreased the 2-h cumulative food intake by 30-62%. Urocortin (3 mug/kg)-induced hypophagia was completely antagonized by astressin B (30 mug/kg ip) and partially (35 and 31%) by antisauvagine-30 (100 or 200 mug/kg ip). The CRF-R1 antagonists CP-154,526 or DMP904 (10 mg/kg ip) had no effect. Capsaicin did not alter urocortin-inhibitory actions while blocking the satiety effect of intraperitoneal CCK. These data indicate that intraperitoneal urocortin-induced decrease in feeding is only partly mediated by CRF-R2, whereas urocortin action to delay gastric emptying of a meal involves primarily CRF-R2. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Div Digest Dis,Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. Cardenal Herrera Univ, Dept Basic Biomed Sci, Valencia 46113, Spain. RP Wang, LX (reprint author), CURE VA, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-26741, DK-41301] NR 57 TC 71 Z9 73 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD NOV PY 2001 VL 281 IS 5 BP R1401 EP R1410 PG 10 WC Physiology SC Physiology GA 483HW UT WOS:000171630200010 PM 11641109 ER PT J AU Tian, W Bonkovsky, HL Shibahara, S Cohen, DM AF Tian, W Bonkovsky, HL Shibahara, S Cohen, DM TI Urea and hypertonicity increase expression of heme oxygenase-1 in murine renal medullary cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE sodium chloride; osmotic; oxidative stress; transcription ID EMBRYO LIVER-CELLS; DUCT MIMCD3 CELLS; NITRIC-OXIDE; TRANSCRIPTIONAL CONTROL; MEDIATED INDUCTION; EPITHELIAL-CELLS; OXIDATIVE STRESS; PRIMARY CULTURES; GENE-EXPRESSION; PROTEIN-KINASE AB Epithelial cells derived from the mammalian kidney medulla are responsive to urea at the levels of signal transduction and gene regulation. Hybridization of RNA harvested from control- and urea-treated murine inner medullary collecting duct (mIMCD3) cells with a cDNA expression array encoding stress-responsive genes suggested that heme oxygenase (HO)-1 mRNA was upregulated by urea. RNase protection assay confirmed this upregulation; hypertonicity also increased HO-1 mRNA expression but neither hypertonic NaCl nor urea were effective in the nonrenal 3T3 cell line. The effect on HO-1 expression appeared to be transcriptionally mediated on the basis of mRNA half-life studies and reporter gene analyses using the promoters of both human and chicken HO-1. Although urea signaling resembles that of heavy metal signaling in other contexts, the effect of urea on HO-1 transcription was independent of the cadmium response element in this promoter. Urea-inducible HO-1 expression was sensitive to antioxidants but not to scavengers of nitric oxide. Urea also upregulated HO-1 protein expression and pharmacological inhibition of HO-1 action with zinc protoporphyrin-sensitized mIMCD3 cells to the adverse effects of hypertonicity but not to urea. Coupled with the prior observation of others that HO-1 expression increases along the renal corticomedullary gradient, these data suggest that HO-1 expression may comprise an element of the adaptive response to hypertonicity and/or urea in renal epithelial cells. C1 Oregon Hlth Sci Univ, Div Nephrol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Mol Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Tohoku Univ, Sch Med, Dept Mol Biol & Appl Physiol, Sendai, Miyagi 980, Japan. RP Cohen, DM (reprint author), Oregon Hlth Sci Univ, Div Nephrol, Mailcode PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM cohend@ohsu.edu RI Shibahara, Shigeki/M-3644-2014 FU NIDDK NIH HHS [DK-52494] NR 49 TC 19 Z9 19 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 2001 VL 281 IS 5 BP F983 EP F991 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 480QJ UT WOS:000171473200023 PM 11592956 ER PT J AU Borrelli, B Hecht, JP Papandonatos, GD Emmons, KM Tatewosian, LR Abrams, DB AF Borrelli, B Hecht, JP Papandonatos, GD Emmons, KM Tatewosian, LR Abrams, DB TI Smoking-cessation counseling in the home - Attitudes, beliefs, and behaviors of home healthcare nurses SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE counseling; nurses; smoking; smoking cessation ID POPULATION-BASED SURVEY; OLDER SMOKERS; INTERVENTIONS; PERCEPTIONS; PREDICTORS; ADVICE; CARE AB Background: Despite advances in smoking treatment, cessation rates remain stagnant, possibly a function of the lack of new channels to reach heavily addicted smokers. This cross-sectional study examined home care nurses' attitudes, beliefs, and counseling behaviors regarding counseling their home care patients who smoke. Methods: Home healthcare nurses (N=98) from the Visiting Nurse Association of Rhode Island were randomly selected to participate in a study helping home-bound medically ill smokers to quit, At baseline, nurses completed a questionnaire that assessed a constellation of cognitive factors (self-efficacy, outcome expectations, perceived effectiveness, risk perception, motivation, and perceived patient adherence) as correlates of self-reported nurse counseling behaviors. Results: Nurses with higher outcome expectations spent more time counseling their patients about quitting (p<0.04). Nurses' self-efficacy was the only variable associated with consistent counseling (p<0.05). While the majority of nurses "asked and advised" their patients, a minority of nurses "assisted or arranged" follow-up. Perceived importance of counseling was associated with a greater likelihood of asking, advising and assisting (p<0.05). None of the nurses who currently smoked (n=13) provided follow-up to their patients. Nurses who reported higher levels of both risk perception (regarding the harmful effects of smoking) and perceived effectiveness were more likely to recommend the nicotine patch. Conclusions: Attitudes and beliefs about smoking are significantly associated with nurse counseling behaviors. Helping nurses to overcome their barriers to smoking counseling may open up new channels for smoking intervention. C1 Miriam Hosp, Brown Med Sch, Ctr Behav Med, Providence, RI 02903 USA. Miriam Hosp, Brown Med Sch, Ctr Prevent Med, Providence, RI 02903 USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Boston, MA USA. RP Borrelli, B (reprint author), Miriam Hosp, Brown Med Sch, Ctr Behav Med, Coro Bldg W,1 Hoppin St,Suite 500, Providence, RI 02903 USA. RI Papandonatos, George/J-2328-2014; OI Papandonatos, George/0000-0001-6770-932X FU NCI NIH HHS [R01 CA74553] NR 29 TC 45 Z9 45 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD NOV PY 2001 VL 21 IS 4 BP 272 EP 277 DI 10.1016/S0749-3797(01)00369-5 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 515WE UT WOS:000173519000006 PM 11701297 ER PT J AU Tobin, MJ AF Tobin, MJ TI Asthma, airway biology, and allergic rhinitis in AJRCCM 2000 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID EXHALED NITRIC-OXIDE; IMMUNODEFICIENCY-VIRUS TYPE-1; OBSTRUCTIVE PULMONARY-DISEASE; PLATELET-ACTIVATING-FACTOR; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; SMOOTH-MUSCLE CELLS; MUCOSAL BLOOD-FLOW; GUINEA-PIG AIRWAYS; QUALITY-OF-LIFE C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 234 TC 8 Z9 9 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2001 VL 164 IS 9 BP 1559 EP 1580 PG 22 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 499RR UT WOS:000172584600005 PM 11719293 ER PT J AU Tobin, MJ AF Tobin, MJ TI Pediatrics, surfactant, and cystic fibrosis in AJRCCM 2000 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID SYNCYTIAL VIRUS BRONCHIOLITIS; ENVIRONMENTAL TOBACCO-SMOKE; FUNCTION REFERENCE VALUES; HYALINE-MEMBRANE DISEASE; EXHALED NITRIC-OXIDE; LUNG-FUNCTION GROWTH; INNER-CITY CHILDREN; YOUNG-CHILDREN; ASTHMATIC-CHILDREN; AIRWAY INFLAMMATION C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 116 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2001 VL 164 IS 9 BP 1581 EP 1594 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 499RR UT WOS:000172584600006 PM 11719294 ER PT J AU Gay, PC Hess, DR Hill, NS AF Gay, PC Hess, DR Hill, NS TI Noninvasive proportional assist ventilation for acute respiratory insufficiency - Comparison with pressure support ventilation SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory failure; mechanical ventilation; noninvasive ventilation; pressure support ventilation; proportional assist ventilation ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED TRIAL; MECHANICAL VENTILATION; ACUTE EXACERBATIONS; DEPENDENT PATIENTS; NASAL VENTILATION; FAILURE; HYPERCAPNIA; SUCCESS; MASK AB Noninvasive positive pressure ventilation (NPPV) is usually applied using pressure support ventilation (PSV). Proportional assist ventilation (PAV) is a newer mode that delivers assisted ventilation in proportion to patient effort. We hypothesized that PAV for NPPV would support gas exchange and avoid intubation as well as PSV and be more comfortable and tolerable for patients. Adult patients with acute respiratory insufficiency were randomized to receive NPPV with PAV delivered using the Respironics Vision ventilator or PSV using a Puritan-Bennett 7200ae critical care ventilator. Each mode was adjusted to relieve dyspnea and improve gas exchange until patients met weaning or intubation criteria, died, or refused to continue. Twenty-one and 23 patients were entered into the PAV and PSV groups, respectively, and had similar diagnoses and baseline characteristics, although pH was slightly lower in the PAV group (7.30 versus 7.35, p = 0.02). Mortality and intubation rates were similar, but refusal rate was lower, reduction in respiratory rate was more rapid, and there were fewer complications in the PAV group. We conclude that use of the PAV mode is feasible for noninvasive therapy of acute respiratory insufficiency. Compared with PSV delivered with the Puritan-Bennett 7200ae, PAV is associated with more rapid improvements in some physiologic variables and is better tolerated. C1 Rhode Isl Hosp, Div Pulm, Providence, RI 02903 USA. Rhode Isl Hosp, Div Crit Care, Providence, RI 02903 USA. Rhode Isl Hosp, Div Sleep Med, Providence, RI 02903 USA. Mayo Clin & Mayo Fdn, Div Pulm, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Crit Care Med, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hill, NS (reprint author), Rhode Isl Hosp, Div Pulm, 593 Eddy St, Providence, RI 02903 USA. NR 31 TC 50 Z9 53 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2001 VL 164 IS 9 BP 1606 EP 1611 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 499RR UT WOS:000172584600009 PM 11719297 ER PT J AU Gottlieb, DJ Wilk, JB Harmon, M Evans, JC Joost, O Levy, D O'Connor, GT Myers, RH AF Gottlieb, DJ Wilk, JB Harmon, M Evans, JC Joost, O Levy, D O'Connor, GT Myers, RH TI Heritability of longitudinal change in lung function - The Framingham Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE spirometry; epidemiologic studies; genetics ID OBSTRUCTIVE PULMONARY-DISEASE; SEGREGATION ANALYSIS; FAMILY; EPIDEMIOLOGY; SMOKING; SAMPLE; TWINS; RISK AB There have been multiple reports of heritability of lung function in cross-sectional analysis, but no prior reports of heritability of rate of change in lung function. We examined heritability of rate of change of lung function in families participating in the Framingham Heart Study. Spirometric measures from two time points were used to calculate annualized rate of change in FEV1, FVC, and FEV1/FVC ratio, adjusting for the effects of age, height, and weight using multiple linear regression models. Standardized residuals from these models were used as phenotypic variables in variance components analysis to assess effects of smoking and heritable factors on rate of change in lung function. Heritable factors explained a modest proportion of the population variance, with heritability estimates for change in FEV1, FVC, and ratio of 0.05, 0.18, and 0.13, respectively. Restricting the analysis to subjects concordant for smoking status during the interval over which lung function was measured, the heritability estimates increased to 0.18, 0.39, and 0.14, respectively, among interim smokers. These data suggest that in middle-aged and older persons in the general population, genetic factors contribute modestly to the overall population variance in rate of lung function decline, and further suggest the importance of gene-environment interactions. C1 VA Boston Healthcare Syst, Res Serv, Boston, MA USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Gottlieb, DJ (reprint author), Ctr Pulm, 715 Albany St,R-304, Boston, MA 02118 USA. OI O'Connor, George/0000-0002-6476-3926 FU NHLBI NIH HHS [HL-49869, N01-HC-38038] NR 23 TC 38 Z9 38 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 1 PY 2001 VL 164 IS 9 BP 1655 EP 1659 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 499RR UT WOS:000172584600017 PM 11719305 ER PT J AU Rybicki, FJ Chung, T Reid, J Jaramillo, D Mulkern, RV Ma, JF AF Rybicki, FJ Chung, T Reid, J Jaramillo, D Mulkern, RV Ma, JF TI 2001 ARRS Executive Council Award II - Fast three-point Dixon MR imaging using low-resolution images for phase correction: A comparison with chemical shift selective fat suppression of pediatric musculoskeletal imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID WATER; SEPARATION; PROTON AB OBJECTIVE. The purpose of this study is to describe and to implement a new fast three-point Dixon MR imaging sequence with online image reconstruction, and to compare this sequence with conventional chemical shift selective (CHESS) suppression of fat in pediatric musculoskeletal imaging SUBJECTS AND METHODS. A three-point Dixon technique using a fast spin-echo sequence with a new phase-correction algorithm providing online image reconstruction was implemented on a 1.5-T scanner. Twelve pediatric patients and young adults were imaged with both the new three-point Dixon and conventional CHESS sequences. Three radiologists unaware of imaging parameters and clinical information independently scored the homogeneity of fat suppression and conspicuity of abnormality using a four-point system. An additional comparison between the two techniques was made using a phantom. RESULTS. The three-point Dixon method showed superior fat suppression and lesion conspicuity (p < 0.001), particularly in the hands and feet, where CHESS is prone to inconsistent fat suppression. The phantom study showed no significant difference in the ratio of suppressed fat signal to background noise and more homogeneous fat suppression using the three-point Dixon method. CONCLUSION. Compared with CHESS, the new fast three-point Dixon sequence with online image reconstruction provides superior fat suppression and lesion conspicuity and can be routinely used in pediatric musculoskeletal imaging. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Texas Childrens Hosp, Edward B Singleton Dept Diagnost Imaging, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Cleveland Clin Fdn, Childrens Hosp, Dept Radiol, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiol, Houston, TX 77030 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Rybicki, FJ (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 18 TC 24 Z9 27 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD NOV PY 2001 VL 177 IS 5 BP 1019 EP 1023 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 485BB UT WOS:000171732700010 PM 11641161 ER PT J AU Al-Ahmadie, HA Stanek, J Liu, J Mangu, PN Niemann, T Young, RH AF Al-Ahmadie, HA Stanek, J Liu, J Mangu, PN Niemann, T Young, RH TI Ovarian 'Tumor' of the adrenogenital syndrome - The first reported case SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE congenital adrenal hyperplasia; adrenogenital syndrome; ovarian tumor; like lesion ID CLINICOPATHOLOGICAL ANALYSIS; NELSONS SYNDROME; CELL TUMOR AB We report the case of a 36-year-old woman with congenital adrenal hyperplasia from 21-hydroxylase deficiency who had been receiving replacement therapy with corticosteroids since birth. At the age of 35 years, she developed abrupt aggravation of her virilizing symptoms and underwent an adrenalectomy and partial left oophorectomy. Persistent virilization and high testosterone levels led to right oophorectomy and completion left oophorectomy 6 months later. Each adnexa contained ovarian or paraovarian soft brown masses that on microscopic examination were identical to the testicular tumor of the adrenogenital syndrome. This represents the first reported case of this pathology (well known in the testis) in the ovary. C1 Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. Univ Cincinnati, Coll Med, Dept Obstet & Gynecol, Cincinnati, OH 45267 USA. Ohio State Univ Hosp, Dept Pathol, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Labs, Boston, MA 02115 USA. RP Stanek, J (reprint author), Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. NR 14 TC 25 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2001 VL 25 IS 11 BP 1443 EP 1450 DI 10.1097/00000478-200111000-00015 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 488GQ UT WOS:000171928200015 PM 11684964 ER PT J AU Matas, AJ Delmonico, FL AF Matas, AJ Delmonico, FL TI Transplant kidneys sooner: Discard fewer kidneys SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID DELAYED GRAFT FUNCTION; ACUTE REJECTION; SURVIVAL; DONORS C1 Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Cambridge, MA 02138 USA. RP Matas, AJ (reprint author), Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA. NR 14 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2001 VL 1 IS 4 BP 301 EP 304 DI 10.1034/j.1600-6143.2001.10401.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 514XX UT WOS:000173467300001 PM 12099370 ER PT J AU Kurtz, J Ito, H Wekerle, T Shaffer, J Sykes, M AF Kurtz, J Ito, H Wekerle, T Shaffer, J Sykes, M TI Mechanisms involved in the establishment of tolerance through costimulatory blockade and BMT: Lack of requirement for CD40L-mediated signaling for tolerance or deletion of donor-reactive CD4(+) cells SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE bone marrow; costimulatory molecule; T lymphocytes; tolerance/suppression; transplantation ID CD8(+) T-CELLS; BONE-MARROW TRANSPLANTATION; RENAL-ALLOGRAFT REJECTION; LONG-TERM SURVIVAL; CD40 LIGAND; MONOCLONAL-ANTIBODY; ANTI-CD154 ANTIBODY; CLONAL DELETION; SKIN ALLOGRAFTS; ACCEPTANCE AB We have previously shown that high levels of multilineage mixed hematopoietic chimerism and systemic T-cell tolerance can be achieved in mice without myeloablation through the use of anti-CD40L and costimulatory blockade alone (plus CTLA41g) or with recipient CD8 depletion and allogeneic bone marrow transplantation. Chimeric mice permanently accept donor skin grafts (> 100 days), and rapidly reject third-party grafts. The mechanisms by which costimulatory blockade facilitates the engraftment of allogeneic hematopoietic cells have not been defined. To further understand the in vivo mechanisms by which the administration of anti-CD40L mAb facilitates the engraftment of donor bone marrow and rapidly tolerizes CD4(+) T-cells, we analyzed the establishment of chimerism and tolerance in CD40L(-/-) mice. We demonstrate here that anti-CD40L mAb treatment is required only to prevent CD40L/CD40 interactions, and that no signal to the T-cell through CD40L is necessary for the induction of CD4(+) tolerance. Peripheral deletion of donor-reactive CD4(+) T-cells occurs rapidly in CD40L(-/-) mice receiving bone marrow transplantation (BMT), indicating that this deletion in the presence of anti-CD40L is not due to targeting of activated CD4(+) cells by the antibody. Complete CD4(+) cell tolerance is observed by both skin graft acceptance and in vitro assays before deletion is complete, indicating that additional mechanisms play a role in inducing CD4(+) T-cell tolerance as the result of BMT in the presence of CD40/CD40L blockade. C1 Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplant Sect,Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplant Sect,Sch Med, Boston, MA 02129 USA. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [HL49915]; NIAID NIH HHS [1T32 AI-07529] NR 39 TC 57 Z9 58 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2001 VL 1 IS 4 BP 339 EP 349 DI 10.1034/j.1600-6143.2001.10409.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 514XX UT WOS:000173467300009 PM 12099378 ER PT J AU Weinger, MB Raemer, DB Barker, SJ AF Weinger, MB Raemer, DB Barker, SJ TI A new Anesthesia & Analgesia section on Technology, Computing, and Simulation SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material C1 Univ Arizona, Arizona Hlth Sci Ctr, Dept Anesthesiol, Tucson, AZ 85724 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. San Diego VA Healthcare Syst, Anesthesia Ergon Res Lab, San Diego, CA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Barker, SJ (reprint author), Univ Arizona, Arizona Hlth Sci Ctr, Dept Anesthesiol, POB 245114, Tucson, AZ 85724 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2001 VL 93 IS 5 BP 1085 EP 1087 DI 10.1097/00000539-200111000-00001 PG 3 WC Anesthesiology SC Anesthesiology GA 486MA UT WOS:000171820500001 PM 11682371 ER PT J AU Roy, P Baskaran, H Tilles, AW Yarmush, ML Toner, M AF Roy, P Baskaran, H Tilles, AW Yarmush, ML Toner, M TI Analysis of oxygen transport to hepatocytes in a flat-plate microchannel bioreactor SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE bioartificial liver; oxygen transport; membrane; mathematical modeling ID ACUTE LIVER-FAILURE; BIOARTIFICIAL LIVER; MASS-TRANSFER; ASSIST DEVICE; SUPPORT; SENSORS; WALLS; FLOW AB Oxygen transfer to cultured hepatocytes in microchannel parallel-plate bioreactors with and without an internal membrane oxygenator was investigated with a mathematical model and the results were corroborated with fluorescence imaging experiments. The consumption of oxygen by hepatocytes was assumed to follow Michaelis-Menten kinetics. Our simulations indicate that under conditions of low Peclet (Pe) number (<80) and fixed Damkohler number (=0.14, corresponding to rat hepatocytes) the cells are hypoxic in the bioreactor without an internal membrane oxygenator. Under the same conditions, the bioreactor with an internal membrane oxygenator can avoid cell hypoxia by appropriate selection of membrane Sherwood number and/or the gas phase oxygen partial pressure, thus providing greater control of cell oxygenation. At high Pe, both bioreactors are well oxygenated. Experimentally determined oxygen concentrations within the bioreactors were in good qualitative agreement with model predictions. At low Pe, cell surface oxygen depletion was predicted from analytically derived criteria. Hepatocytes with oxygen dependent functional heterogeneity may exhibit optimal function in the bioreactor with the internal membrane oxygenator. (C) 2001 Biomedical Engineering Society. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA USA. RP Toner, M (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR13322]; NIDDK NIH HHS [DK43371] NR 36 TC 45 Z9 45 U1 0 U2 9 PU BIOMEDICAL ENGINEERING SOC AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV PY 2001 VL 29 IS 11 BP 947 EP 955 DI 10.1114/1.1415524 PG 9 WC Engineering, Biomedical SC Engineering GA 502UE UT WOS:000172760500003 PM 11791677 ER PT J AU Hochberg, FH Tabatabai, G AF Hochberg, FH Tabatabai, G TI Therapy of PCNSL at the Massachusetts General Hospital with high dose methotrexate and deferred radiotherapy SO ANNALS OF HEMATOLOGY LA English DT Article; Proceedings Paper CT 1st International Symposium on Biology and Treatment of Aggressive Lymphomas (Lymphoma 2000) CY SEP 23-27, 2000 CL SAARBRUCKEN, GERMANY ID NERVOUS-SYSTEM LYMPHOMA; CHEMOTHERAPY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hochberg, FH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD NOV PY 2001 VL 80 SU 3 BP B111 EP B112 PG 2 WC Hematology SC Hematology GA 500GR UT WOS:000172618700027 PM 11757690 ER PT J AU Cataldo, A Rebeck, GW Ghetti, B Hulette, C Lippa, C Van Broeckhoven, C van Duijn, C Cras, P Bogdanovic, N Bird, T Peterhoff, C Nixon, R AF Cataldo, A Rebeck, GW Ghetti, B Hulette, C Lippa, C Van Broeckhoven, C van Duijn, C Cras, P Bogdanovic, N Bird, T Peterhoff, C Nixon, R TI Endocytic disturbances distinguish among subtypes of Alzheimer's disease and related disorders SO ANNALS OF NEUROLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; BETA-SECRETASE CLEAVAGE; APOE GENOTYPE; ENDOPLASMIC-RETICULUM; DOWN-SYNDROME; ONSET; MUTATION; PATHWAY; ALLELE; AGE AB The endocytic pathway is important in amyloid precursor protein (APP) processing and beta -amyloid formation. Our studies have shown that endocytic pathway activation is a prominent and early feature of neurons in vulnerable regions of the brain in sporadic Alzheimer's disease. We report that endocytic pathway abnormalities are present not only in neurons, but in cerebral endothelia in Alzheimer's disease caused by certain APP mutations. The presence or absence of endocytic abnormalities distinguish subtypes of familial Alzheimer's disease linked to APP mutations from presenilin mutations, supporting the notion that different cellular pathways are involved in the altered processing of APP leading to increased beta -amyloid generation in certain of these different Alzheimer's disease subtypes. C1 Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr,Lab Mol Neuropathol, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimers Res Ctr, Charlestown, MA USA. Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Med Coll Penn & Hahnemann Univ, Dept Neurol, Philadelphia, PA 19102 USA. Univ Antwerp VIB, Born Bunge Fdn, Dept Mol Genet, B-2020 Antwerp, Belgium. Erasmus Univ, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Univ Antwerp, Born Bunge Fdn, Neurobiol Lab, B-2020 Antwerp, Belgium. Karolinska Inst, Dept Geriatr Med, Inst Clin Neurosci & Family Med, S-10401 Stockholm, Sweden. VA Med Ctr, Dept Geriatr, Seattle, WA USA. Nathan S Kline Inst Psychiat Res, Ctr Dermatia Res, Orangeburg, NY 10962 USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. RP Cataldo, A (reprint author), Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr,Lab Mol Neuropathol, 115 Mill St, Belmont, MA 02478 USA. EM acataldo@mclean.harvard.edu NR 20 TC 44 Z9 44 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2001 VL 50 IS 5 BP 661 EP 665 DI 10.1002/ana.1254 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 488WV UT WOS:000171960600015 PM 11706973 ER PT J AU Wolfe, F Choi, HK AF Wolfe, F Choi, HK TI Benchmarking and the percentile assessment of RA: Adding a new dimension to rheumatic disease measurement SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID EARLY INFLAMMATORY POLYARTHRITIS; LONG-TERM OUTCOMES; ARTHRITIS; POPULATION C1 Univ Kansas, Sch Med, Natl Data Bank Rheumat Dis, Arthrit Res Ctr Fdn, Wichita, KS 67214 USA. Massachusetts Gen Hosp, Dept Med, Arthrit Unit, Boston, MA USA. RP Wolfe, F (reprint author), Univ Kansas, Sch Med, Natl Data Bank Rheumat Dis, Arthrit Res Ctr Fdn, 1035 N Emporia,Suite 230, Wichita, KS 67214 USA. NR 21 TC 7 Z9 7 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2001 VL 60 IS 11 BP 994 EP 995 DI 10.1136/ard.60.11.994 PG 2 WC Rheumatology SC Rheumatology GA 485BH UT WOS:000171733300002 PM 11602461 ER PT J AU de Boer, JF Saxer, CE Nelson, JS AF de Boer, JF Saxer, CE Nelson, JS TI Stable carrier generation and phase-resolved digital data processing in optical coherence tomography SO APPLIED OPTICS LA English DT Article AB We present a technique for improved carrier generation by eliminating the instability of a mechanical device in favor of an electro-optical phase modulator in the reference arm of an optical coherence tomography system. A greater than threefold reduction in the phase variance between consecutive A-line scans at a repetition rate of 1 kHz was achieved. Stable and reproducible interference fringe generation permits phase-resolved digital data processing. A correction algorithm was applied to the interferometric signal to compensate for the departure of the source spectrum from an ideal Gaussian shape, resulting in up to 8-dB sidelobe suppression at the expense of a 1-dB increase in the noise floor. In addition, we could eliminate completely the broadening effect of group-delay dispersion on the coherence function by introducing a quadratic phase shift in the Fourier domain of the interferometric signal. (C) 2001 Optical Society of America. C1 Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. RP de Boer, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, 50 Blossom St,BAR 724, Boston, MA 02114 USA. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 9 TC 56 Z9 56 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 NOV 1 PY 2001 VL 40 IS 31 BP 5787 EP 5790 DI 10.1364/AO.40.005787 PG 4 WC Optics SC Optics GA 487BH UT WOS:000171853400029 PM 18364870 ER PT J AU Tsao, H Arndt, KA AF Tsao, H Arndt, KA TI The genomics issue SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 48 Blossom St,Bartlett 622, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 NOV PY 2001 VL 137 IS 11 BP 1409 EP 1409 PG 1 WC Dermatology SC Dermatology GA 492NH UT WOS:000172174100001 ER PT J AU Marneros, AG Norris, JEC Olsen, BR Reichenberger, E AF Marneros, AG Norris, JEC Olsen, BR Reichenberger, E TI Clinical genetics of familial keloids SO ARCHIVES OF DERMATOLOGY LA English DT Article ID RUBINSTEIN-TAYBI SYNDROME; HYPERTROPHIC SCARS AB Background: Keloids are proliferative fibrous growths that result from an excessive tissue response to skin trauma. Most keloids occur sporadically, but some cases are familial. However, the genetics of keloid formation have only rarely been documented, and the mode of inheritance is not known. Objective: To elucidate the clinical genetic characteristics of keloid wound-healing disorder. Observations: We studied the clinical and genetic characteristics of 14 pedigrees with familial keloids. The ethnicity of these families is mostly African American (n = 10), but also white (n = 1), Japanese (n = 2), and African Caribbean (n = 1). The pedigrees account for 341 family members, of whom 96 displayed keloids. Of the affected family members, 36 are male and 60 are female. The age of onset varies from early childhood to late adulthood. There is variable expression of keloids within the same families: some affected members have only minor earlobe keloids, whereas others have very severe keloids affecting large areas of the body. In the described pedigrees, 7 individuals are obligate unaffected carriers, revealing nonpenetrance in about 6.8% of keloid gene carriers. Syndromes associated with keloids, namely Rubinstein-Taybi and Geominne syndrome, were not found in these families. Additionally, linkage to the gene loci of these syndromes and X-chromosomal linkage were excluded. Conclusions: The pattern of inheritance observed in these families is consistent with an autosomal dominant mode with incomplete clinical penetrance and variable expression. This is the most comprehensive collection of keloid families described to date, and it allows for the first time the elucidation of the clinical genetic characteristics of the familial form of this wound-healing disorder. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. Forsyth Inst, Boston, MA USA. Univ Cologne, Dept Dermatol, D-5000 Cologne, Germany. St Lukes Roosevelt Hosp, Dept Plast Surg, New York, NY USA. RP Marneros, AG (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR 45286, AR 36820, AR 36819] NR 23 TC 92 Z9 124 U1 0 U2 4 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 NOV PY 2001 VL 137 IS 11 BP 1429 EP 1434 PG 6 WC Dermatology SC Dermatology GA 492NH UT WOS:000172174100005 PM 11708945 ER PT J AU Stratigos, AJ Baden, HP AF Stratigos, AJ Baden, HP TI Unraveling the molecular mechanisms of hair and nail genodermatoses SO ARCHIVES OF DERMATOLOGY LA English DT Review ID HYPOHIDROTIC ECTODERMAL DYSPLASIA; PACHYONYCHIA-CONGENITA TYPE-2; KERATIN-17 MUTATIONS CAUSE; NETHERTON-SYNDROME; XERODERMA-PIGMENTOSUM; MISSENSE MUTATION; PATELLA SYNDROME; SKIN FRAGILITY; GENE; TRICHOTHIODYSTROPHY C1 Univ Athens, Sch Med, Andreas Sygros Hosp, Dept Dermatol, Athens 16121, Greece. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Stratigos, AJ (reprint author), Univ Athens, Sch Med, Andreas Sygros Hosp, Dept Dermatol, 5 Dragoumi St, Athens 16121, Greece. NR 81 TC 10 Z9 11 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 NOV PY 2001 VL 137 IS 11 BP 1465 EP 1471 PG 7 WC Dermatology SC Dermatology GA 492NH UT WOS:000172174100009 PM 11708949 ER PT J AU MacLean, JA Eidelman, FJ AF MacLean, JA Eidelman, FJ TI The genetics of atopy and atopic eczema SO ARCHIVES OF DERMATOLOGY LA English DT Review ID ASTHMA; DERMATITIS; LINKAGE; ASSOCIATION; RHINITIS; FAMILIES; ALLERGY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Cleveland Clin, Dept Allergy & Immunol, Ft Lauderdale, FL USA. RP MacLean, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, BUL 422,50 Blossom, Boston, MA 02115 USA. NR 28 TC 14 Z9 14 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 NOV PY 2001 VL 137 IS 11 BP 1474 EP 1476 PG 3 WC Dermatology SC Dermatology GA 492NH UT WOS:000172174100010 PM 11708950 ER PT J AU Tsao, H AF Tsao, H TI Genetics of nonmelanoma skin cancer SO ARCHIVES OF DERMATOLOGY LA English DT Review ID BASAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; XERODERMA-PIGMENTOSUM PATIENTS; MUIR-TORRE-SYNDROME; RAS ONCOGENE MUTATIONS; B-CHAIN GENE; P53 MUTATIONS; MICROSATELLITE INSTABILITY; BETA-CATENIN; DERMATOFIBROSARCOMA PROTUBERANS C1 Massachusetts Gen Hosp, Dept Dermatol, Melanoma Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Melanoma Ctr, 48 Blossom St,Barlett 622, Boston, MA 02114 USA. NR 91 TC 19 Z9 20 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 NOV PY 2001 VL 137 IS 11 BP 1486 EP 1492 PG 7 WC Dermatology SC Dermatology GA 492NH UT WOS:000172174100012 PM 11708952 ER PT J AU Niendorf, KB Shannon, KM AF Niendorf, KB Shannon, KM TI The role of genetic testing and effect on patient care SO ARCHIVES OF DERMATOLOGY LA English DT Review ID BANNAYAN-ZONANA-SYNDROME; COWDEN-DISEASE; GERMLINE MUTATIONS; PTEN C1 Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. RP Niendorf, KB (reprint author), Massachusetts Gen Hosp, Ctr Canc Risk Anal, Zero Emerson Pl,Suite 104, Boston, MA 02114 USA. EM kniendorf@partners.org NR 14 TC 1 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 2001 VL 137 IS 11 BP 1515 EP 1519 PG 5 WC Dermatology SC Dermatology GA 492NH UT WOS:000172174100018 PM 11708959 ER PT J AU Glazer, WM Woods, SW AF Glazer, WM Woods, SW TI Should sisyphus have taken melatonin? SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID TARDIVE-DYSKINESIA; VITAMIN-E C1 Massachusetts Gen Hosp, Dept Psychiat, Chilmark, MA 02535 USA. RP Glazer, WM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 100 Beach Plum Ln, Chilmark, MA 02535 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2001 VL 58 IS 11 BP 1054 EP 1055 DI 10.1001/archpsyc.58.11.1054 PG 2 WC Psychiatry SC Psychiatry GA 490MR UT WOS:000172056100008 PM 11695952 ER PT J AU Steinbart, EJ Smith, CO Poorkaj, P Bird, TD AF Steinbart, EJ Smith, CO Poorkaj, P Bird, TD TI Impact of DNA testing for early-onset familial Alzheimer disease and frontotemporal dementia SO ARCHIVES OF NEUROLOGY LA English DT Article ID HUNTINGTONS-DISEASE; CANDIDATE GENE; EXPERIENCE; MUTATIONS; DISORDERS; DISTRESS; SUICIDE; SCALE; TAU AB Background: DNA testing of persons at risk for hereditary, degenerative neurologic diseases is relatively new. Only anecdotal reports of such testing in familial Alzheimer disease (FAD) exist, and little is know about the personal and social impact of such testing. Methods: in a descriptive, observational study, individuals at 50% risk for autosomal dominant, early-onset FAD or frontotemporal dementia with parkinsonism linked to chromosome 17 underwent DNA testing for the genetic mutations previously identified in affected family members. Individuals were followed up for (1)/(2) to 3 years and were interviewed regarding attitudes toward the testing process and the impact of the results. Results: Twenty-one (8.4%) of 251 persons at risk for FAD or frontotemporal dementia requested genetic testing. The most common reasons for requesting testing were concern about early symptoms of dementia, financial or family planning, and relief from anxiety. Twelve individuals had positive DNA test results, and 6 of these had early symptoms of demential 8 had negative results; and I has not vet received results. Of 14 asymptomatic individuals completing testing, 13 believed the testing was beneficial. Two persons reported moderate anxiety and 1 reported moderate depression. As expected, persons with negative test results had happier experiences overall, but even they had to deal with ongoing anxiety and depression. Thus far, there have been no psychiatric hospitalizations, suicide attempts, or denials of insurance. Conclusions: Genetic testing in early-onset FAD and frontotemporal dementia can be completed successfully. Most individuals demonstrate effective coping skills and find the testing to be beneficial, but long-term effects remain unknown. C1 Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Bird, TD (reprint author), VA Med Ctr, Geriatr Res 182,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [AG05136]; PHS HHS [H133B980008] NR 27 TC 57 Z9 57 U1 0 U2 4 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 NOV PY 2001 VL 58 IS 11 BP 1828 EP 1831 DI 10.1001/archneur.58.11.1828 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 490MH UT WOS:000172055300016 PM 11708991 ER PT J AU Poorkaj, P Tsuang, D Wijsman, E Steinbart, E Garruto, RM Craig, UK Chapman, NH Anderson, L Bird, TD Plato, CC Perl, DP Weiderholt, W Galasko, D Schellenberg, GD AF Poorkaj, P Tsuang, D Wijsman, E Steinbart, E Garruto, RM Craig, UK Chapman, NH Anderson, L Bird, TD Plato, CC Perl, DP Weiderholt, W Galasko, D Schellenberg, GD TI TAU as a susceptibility gene for amyotropic lateral sclerosis-parkinsonism dementia complex of Guam SO ARCHIVES OF NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; FRONTOTEMPORAL DEMENTIA; LINKAGE DISEQUILIBRIUM; NEURODEGENERATIVE DISORDERS; FTDP-17 MUTATIONS; CHROMOSOME-17; CALCIUM; POLYMORPHISM; METABOLISM; FAMILIES AB Background: A Guam variant of amyotrophic lateral sclerosis (ALS-G) and parkinsonism. dementia complex (PDC-G) are found in the Chamorro people of Guam. Both disorders have overlapping neuropathologic findings, with neurofibrillary tangles in spinal cord and brain. The cause of ALS-G-PDC-G is unknown, although inheritance and environment appear important. Because neurofibrillary tangles containing tau protein are present in ALS-G-PDC-G, and because mutations in the tau gene (TAU) cause autosomal dominant frontotemporal dementia, TAU was examined as a candidate gene for ALS-G-PDC-G. Methods: TAU was evaluated by DNA sequence analysis in subjects with ALS-G-PDC-G, by linkage analysis of TAU polymorphisms in an extended pedigree from the village of Umatac, and by evaluation of linkage disequilibrium with polymorphic markers flanking and within TAU. Results: Linkage disequilibrium between ALS-G-PDC-G and the TAU polymorphism CA3662 was observed. For this 2-allele system, PDC and ALS cases were significantly less likely than Guamanian controls to have the 1 allele (4.9% and 2% vs 11.5%, respectively; Fisher exact P=.007). DNA sequence analysis of TAU coding regions did not demonstrate a mutation responsible for ALS-C-PDC-G. Analysis of TAU genotypes in an extended pedigree of subjects from Umatac showed obligate recombinants between TAU and ALS-G-PDC-G. Linkage analysis of the Umatac pedigree indicates that TAU is not the major gene for ALS-G-PDC-G. Conclusions: The genetic association between ALS-GPDC-G implicates TAU in the genetic susceptibility to ALS-G-PDC-G. TAU may be a modifying gene increasing risk for ALS-G-PDC-G in the presence of another, as yet, unidentified gene. C1 Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle Div, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ Clin Ctr, Seattle Div, Seattle, WA USA. Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. SUNY Binghamton, Dept Anthropol, Binghamton, NY USA. SUNY Binghamton, Dept Biol Sci, Binghamton, NY USA. NINCDS, NIH, Bethesda, MD 20892 USA. Univ Guam, Dept Publ Hlth, Mangilao, GU USA. Univ San Diego, Dept Neurosci, San Diego, CA 92110 USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Mt Sinai Sch Med, Dept Psychol, New York, NY USA. RP Schellenberg, GD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle Div, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016 OI Tsuang, Debby/0000-0002-4716-1894 FU PHS HHS [P010135316] NR 57 TC 48 Z9 49 U1 0 U2 1 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 NOV PY 2001 VL 58 IS 11 BP 1871 EP 1878 DI 10.1001/archneur.58.11.1871 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 490MH UT WOS:000172055300022 PM 11708997 ER PT J AU Wiggs, JL Vollrath, D AF Wiggs, JL Vollrath, D TI Molecular and clinical evaluation of a patient hemizygous for TIGR/MYOC SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; TIGR GENE; MUTATIONS; PROTEIN; CHROMOSOME-1; DROSOPHILA; EXPRESSION; PREVALENCE; DOSAGE; CELLS AB Objective: To determine if a patient with an interstitial deletion of chromosome 1 is hemizygous for the TIGR/MYOC gene and if that patient has glaucoma. Methods: A patient with an interstitial deletion of chromosome 1 was clinically examined for evidence of glaucoma. DNA samples from the patient and her family were used for molecular studies to determine the boundaries of the chromosome 1 deletion using polymorphic markers located on chromosome 1q21 to 1q24. Additional markers located in the vicinity of the TIGR/MYOC gene, including 2 derived from the ends of the gene, were used to determine if it was included in the deletion. Results: The patient and her family showed no evidence of glaucoma. Molecular analysis demonstrated that a complex deletion of the maternal copy of chromosome 1 included the entire TIGR/MYOC gene. Conclusions: We have determined that the patient has only 1 functional copy of TIGR/MYOC, The lack of clinical evidence of glaucoma suggests that haploinsufficiency of the TIGR/MYOC protein is not the cause of early-onset glaucoma associated with mutations in TIGR/MYOC. Clinical Relevance: Missense and nonsense mutations in the TIGR/MYOC gene have been associated with juvenile- and adult-onset primary open-angle glaucoma. Although many different mutations have been correlated with the disease, the underlying genetic mechanism (haploinsufficiency, gain of function, or a dominant negative effect) remains unknown. Information regarding the genetic mechanism responsible for TIGR/MYOC-associated glaucoma is necessary for further studies designed to develop transgenic animal models and gene-related therapy. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA USA. RP Wiggs, JL (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 09847] NR 32 TC 52 Z9 54 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 NOV PY 2001 VL 119 IS 11 BP 1674 EP 1678 PG 5 WC Ophthalmology SC Ophthalmology GA 490ML UT WOS:000172055600011 PM 11709019 ER PT J AU Wiggs, JL AF Wiggs, JL TI The Human Genome Project and eye disease - Clinical implications SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID GENE-THERAPY C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu NR 10 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2001 VL 119 IS 11 BP 1710 EP 1711 PG 2 WC Ophthalmology SC Ophthalmology GA 490ML UT WOS:000172055600018 PM 11709025 ER PT J AU Lin, AL Johnson, DA Wu, Y Wong, G Ebersole, JL Yeh, CK AF Lin, AL Johnson, DA Wu, Y Wong, G Ebersole, JL Yeh, CK TI Measuring short-term gamma-irradiation effects on mouse salivary gland function using a new saliva collection device SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE whole saliva collection; mice; radiation; longitudinal approach; flow rates; salivary composition ID PAROTID-GLAND; X-IRRADIATION; ACINAR-CELLS; RAT SALIVA; PROTEIN; PEROXIDASE; SECRETION AB A restraining device was designed specifically for the collection of whole saliva from mice without using anesthesia. As the procedure does not involve surgical cannulation of the salivary glands, saliva can be collected from the same mouse at different times. The time between the injection of a secretory stimulant (pilocarpine) and the appearance of saliva in the mouth (lag time) was 100.5 +/- 8.5 s (mean +/- S.E.M., n = 10) for control mice. The volume of saliva collected in the first 5 min was three times greater than that collected between 15 and 20 min. The average flow rate for a collection period of 15 min was 16.7 +/- 1.8 ulmin (n = 10). The flow rate was decreased 50%. (P < 0.005) whereas the lag time was increased more than 300% (P < 0.05) at 24 h after irradiation. The concentrations of a 23.5-kDa protein and a mucin were decreased after irradiation whereas there was no significant effect on the concentration of amylase or peroxidase. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Dent Diagnost Sci 7919, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Community Dent 7917, San Antonio, TX 78229 USA. Univ Kentucky, Coll Dent, Ctr Oral Hlth Res, Lexington, KY 40536 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin 182, San Antonio, TX 78229 USA. RP Yeh, CK (reprint author), Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Dent Diagnost Sci 7919, 4450 Med Dr, San Antonio, TX 78229 USA. NR 24 TC 27 Z9 27 U1 1 U2 5 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 NOV PY 2001 VL 46 IS 11 BP 1085 EP 1089 DI 10.1016/S0003-9969(01)00063-2 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 483MU UT WOS:000171639500012 PM 11543716 ER PT J AU Hartnick, CJ Myseros, JS Myer, CM AF Hartnick, CJ Myseros, JS Myer, CM TI Endoscopic access to the infratemporal fossa and skull base - A cadaveric study SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY MAY 09-12, 2001 CL SCOTTSDALE, ARIZONA SP Amer Soc Pediatr Otolaryngol ID TRIGEMINAL NEURALGIA; TEMPORAL BONE AB Objectives: To demonstrate that the regions of the infratemporal fossa and skull base at the level of the foramen ovale can be visualized endoscopically and that structures can be manipulated within these regions using endoscopic instruments. Methods: Cadaveric dissection of 3 human cadavers using an endoscopic optical dissector. In all, 6 endoscopic infratemporal fossa and skull base approaches were performed. Setting: Human temporal bone laboratory Results: A Gillies incision was coupled with a lateral brow incision, and then subperiosteal planes were developed. Endoscopic visualization and instrumentation was then performed. The infratemporal fossa was readily identified. The skull base at the level of the foramen ovale and the branches of the third division of the trigeminal nerve were seen distinctly, A probe was placed with ease within the foramen ovale itself. Conclusions: Endoscopic access to the infratemporal fossa is readily accomplished, with excellent visualization and instrumentation ability. This novel technique provides access to this remote region for evaluation, possible biopsy, and potential treatment of infratemporal fossa lesions. C1 Childrens Hosp, Med Ctr, Dept Pediat Otolaryngol, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Dept Pediat Neurosurg, Cincinnati, OH 45229 USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 16 Z9 20 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2001 VL 127 IS 11 BP 1325 EP 1327 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 490LW UT WOS:000172054200003 PM 11701068 ER PT J AU Creasey, GH Grill, JH Korsten, M Sang, H Betz, R Anderson, R Walter, J AF Creasey, GH Grill, JH Korsten, M Sang, H Betz, R Anderson, R Walter, J CA Implanted Neuroprosthesis Res Grp TI An implantable neuroprosthesis for restoring bladder and bowel control to patients with spinal cord injuries: A multicenter trial SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE bladder, neurogenic; electric stimulation; rehabilitation; rhizotomy; spinal cord injuries; urinary incontinence ID ANTERIOR ROOT STIMULATORS; ELECTRICAL-STIMULATION; NERVE ROOTS; RHIZOTOMY; PARAPLEGIA AB Objective: To evaluate the safety and efficacy of an implanted neuroprosthesis for management of the neurogenic bladder and bowel in individuals with spinal cord injury (SCI). Design: Prospective Study comparing bladder and bowel control before and at 3. 6. and 12 months after implantation of the neuroprosthesis. Setting: Six US hospitals specializing in treatment of SCI. Patients: Twenty-three neurologically stable patients with complete suprasacral SCIs. Intervention: Implantation of an externally controlled neuroprosthesis for stimulating the sacral nerves and posterior sacral rhizotomy. Main Outcome Measures: Ability to urinate more than 200mL on demand and a resulting postvoid residual volume of less than 50mL. Results: At 1-year follow-up, 18 of 21 patients could urinate more than 200mL with the neuroprosthesis. and 15 of 21 had postvoid volumes less than 50mL (median, 15mL). Urinary tract infection. catheter use. reflex incontinence, anticholinergic drug use, and autonomic dysreflexia were substantially reduced. At 1-year follow-up, 15 of 17 patients reduced the time spent with bowel management. Conclusions: Neural stimulation and posterior rhizotomy is a safe and effective method of bladder and bowel management after suprasacral SCI. (C) 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Shriners Hosp Children, Philadelphia Unit, Philadelphia, PA USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. VA San Diego Hlth Care Syst, San Diego, CA USA. Vet Affairs Med Ctr, Bronx, NY USA. NeuroControl Corp, Cleveland, OH USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Metrohlth Med Ctr, Louis Stokes Dept Vet Affairs Med Ctr, Cleveland, OH 44109 USA. RP Creasey, GH (reprint author), Metrohlth Med Ctr, Louis Stokes Dept Vet Affairs Med Ctr, 2500 Metrohlth Dr, Cleveland, OH 44109 USA. NR 24 TC 62 Z9 72 U1 0 U2 4 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 NOV PY 2001 VL 82 IS 11 BP 1512 EP 1519 DI 10.1053/apmr.2001.25911 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 488WK UT WOS:000171959600002 PM 11689969 ER PT J AU Masel, BE Scheibel, RS Kimbark, T Kuna, ST AF Masel, BE Scheibel, RS Kimbark, T Kuna, ST TI Excessive daytime sleepiness in adults with brain injuries SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Academy-of-Neurology CY APR 25-MAY 02, 1998 CL MINNEAPOLIS, MINNESOTA SP Amer Acad Neurol DE Xbrain injuries; disorders of excessive somnolence; rehabilitation; sleep apnea syndromes; sleep disorders ID CLOSED-HEAD-INJURY; LATENCY TEST; SCALE; POPULATION; PREVALENCE AB Objectives: To determine the prevalence, demographics, and causes of excessive daytime sleepiness in adults with brain injuries after the acute phase of their injury and to investigate the relations between self-report and objective measures of hypersomnolence. Design: A case series of patients enrolled consecutively into a residential rehabilitation program. Setting: University sleep laboratory, live-in rehabilitation center. Patients: Adults with brain injuries (n = 71); mean time +/- standard deviation from injury to study, 38 +/- 60 months. Interventions: A polysomnogram and Multiple Sleep Latency Test (MSLT) were performed in each subject. Each subject also completed the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) questionnaires. Main Outcome Measures: Sleep patterns, by polysomnogram. Daytime hypersomnolence, diagnosed by mean sleep latency on the MSLT less than or equal to 10 minutes. Sleep apnea-hypopnea syndrome, diagnosed by Apnea-Hypopnea Index greater than 10 events/hr. Periodic limb movement disorder, diagnosed by a Periodic Leg Movement Index greater than 10 events/hr. Results: Mean sleep latency was : 10 minutes in 47% of the cohort and less than or equal to 5 minutes in 18.3%. Subjects were classified into 3 groups: nonhypersomnolent (n = 38, 53%), hypersomnolent with abnormal indices (n = 12, 17%), or hypersomnolent with normal indices (n = 21, 30%). Among the 3 groups, no significant differences were present in Glasgow Coma Scale score, length of coma, or time since brain injury. No differences across groups were found in nature of the injury, gender, or medications. No significant correlation existed between the ESS or PSQI results and mean sleep latency on the MSLT. Conclusions: Hypersomnia is common in adults with brain injuries, with a relatively high prevalence of sleep apnea-hypopnea syndrome, periodic limb movement disorder, and posttraurnatic hypersomnia. Subjects with objectively measured sleepiness were not identified on self-reporting questionnaires, suggesting their inability to perceive their hypersomnolence. (C) 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Transit Learning Ctr Galveston, Galveston, TX 77550 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Masel, BE (reprint author), Transit Learning Ctr Galveston, 1528 PO, Galveston, TX 77550 USA. FU NCRR NIH HHS [RR-73] NR 31 TC 70 Z9 71 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2001 VL 82 IS 11 BP 1526 EP 1532 DI 10.1053/apmr.2001.26093 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 488WK UT WOS:000171959600004 PM 11689971 ER PT J AU Hess, MJ Foo, D AF Hess, MJ Foo, D TI Shunting for syringomyelia in patients with spinal cord injuries: Self-reported, long-term effects in 8 patients SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Spinal-Injury-Association CY APR 16, 2000 CL CHICAGO, ILLINOIS SP Amer Spinal Injury Assoc DE cerebrospinal fluid shunts; decompression, surgical; rehabilitation; spinal cord injuries; syringomyelia ID POSTTRAUMATIC SYRINGOMYELIA AB Objective: To investigate the long-term effects of shunting on neurologic outcome of syringomyelia, a complication of spinal cord injury (SCI). Design: Retrospective data collection using telephonic survey. Setting: University based medical center. Participants: Eight of 15 patients who had shunts placed between 1976 and 1999. Interventions: Review of clinical records and self-reported telephone interview. Main Outcomes Measures: Initial clinical presentation, recovery after shunt placement. and subsequent neurologic status were recorded. Patients were asked to rate symptomatic improvement after surgery on a 100-point analog scale; they were also asked whether they would have the surgery again. Results: Presenting symptoms were weakness in all 8 patients, pain in 5 patients, and numbness in 5 patients. After shunting, 6 patients had improved strength, all had less pain, and 2 had less numbness. Six patients experienced neurologic decline an average of 2 years after shunt placement, 3 because of shunt failure, 2 from a new syrinx, and 1 from both shunt failure and new syrinx. Two of the 3 patients who underwent second shunt placements for a new syrinx had full neurologic recovery. Six patients said they would repeat the shunting procedure if necessary, I was uncertain, and I would not. Conclusion: Initial improvements noted after shunting provide long-lasting effects, even though many patients may need a second procedure. Less pain and improved strength are more significant than decreased numbness. C1 Boston Healthcare VA Med Ctr, Dept Spinal Cord Injury, W Roxbury, MA 02132 USA. RP Hess, MJ (reprint author), VA Boston Healthcare Syst, W Roxbury Div, W Roxbury, MA 02132 USA. NR 12 TC 1 Z9 1 U1 0 U2 2 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 NOV PY 2001 VL 82 IS 11 BP 1633 EP 1636 DI 10.1053/apmr.2001.25075 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 488WK UT WOS:000171959600020 PM 11689987 ER PT J AU Peters, JH Carsons, S Kalunian, K McDougall, S Yoshida, M Ko, F van der Vliet-Hristova, M Hahn, TJ AF Peters, JH Carsons, S Kalunian, K McDougall, S Yoshida, M Ko, F van der Vliet-Hristova, M Hahn, TJ TI Preferential recognition of a fragment species of osteoarthritic synovial fluid fibronectin by antibodies to the alternatively spliced EIIIA segment SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ARTICULAR-CARTILAGE; MESSENGER-RNA; MONOCLONAL-ANTIBODIES; ISOFORM DISTRIBUTION; SIGNAL-TRANSDUCTION; OSTEO-ARTHRITIS; EDA SEGMENT; V-SEGMENT; EXPRESSION; PROTEIN AB Objective. To characterize the species of synovial fluid (SF) fibronectin (FN) bearing the alternatively spliced EIIIA segment. Methods. SF from patients with osteoarthritis (OA) and rheumatoid arthritis (RA), as well as corresponding affinity isolation products, were subjected to I-dimensional and 2-dimensional electrophoresis followed by Western blot analysis. Results. Regardless of the clinical type of arthritis, a polyclonal antibody that recognizes antigenic determinants throughout the FN molecule produced staining of predominantly similar to 200+ and similar to 170-kd species in reduced 1-dimensional electrophoresis. Despite the overall prevalence of the larger species, 4 monoclonal antibodies (mAb) reactive with sequences lying near the center of the EIIIA segment exhibited a relative failure to recognize the larger of these 2 species in OA, but not RA, SF. The absence of recognition of EIIIA sequences within the similar to 200+ kd forms of OA SF FN was unrelated to their derivation from dimers, since anti-EIIIA, mAb recognized the smaller fragment species in preference to both monomeric and dimeric forms. The similar to 170-kd EIIIA+ fragments were observed to have minimal gelatin-binding capacity and appeared on 2-dimensional electrophoresis to extend from the N-terminus of FN through at least the center of the EIIIA segment. Similar results were obtained for samples obtained by needle aspiration or arthroscopic lavage, suggesting a widespread applicability of these findings. Conclusion. The similar to 170-kd EIIIA+ species of FN could potentially constitute a soluble "vehicle" by which chondrocyte-regulating EIIIA sequences, liberated from inhibitory flanking C-terminal sequences, could reach cells in the arthritic joint. Additionally, "FN species-specific" recognition of this segment within OA SF could constitute a marker by which to gauge the activity of the OA disease process. C1 Sacramento VA Med Ctr, Mather, CA 95655 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Davis, Davis, CA 95616 USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. RP Peters, JH (reprint author), Sacramento VA Med Ctr, 151-SMC,10535 Hosp Way, Mather, CA 95655 USA. FU NIA NIH HHS [P60-AG-10415]; NIAMS NIH HHS [AR-42469] NR 38 TC 9 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2001 VL 44 IS 11 BP 2572 EP 2585 DI 10.1002/1529-0131(200111)44:11<2572::AID-ART438>3.0.CO;2-Y PG 14 WC Rheumatology SC Rheumatology GA 498CC UT WOS:000172491400015 PM 11710714 ER PT J AU Silverman, SL Minshall, ME Shen, W Harper, KD Xie, S AF Silverman, SL Minshall, ME Shen, W Harper, KD Xie, S CA Hlth-Related Quality Life Subgroup TI The relationship of health-related quality of life to prevalent and incident vertebral fractures in postmenopausal women with osteoporosis - Results from the multiple outcomes of raloxifene evaluation study SO ARTHRITIS AND RHEUMATISM LA English DT Article ID OF-LIFE; BACK PAIN; QUESTIONNAIRE; DEFORMITIES; ASSOCIATION; IMPAIRMENT; DENSITY; TRIAL AB Objective. To examine the effect of both Prevalent and incident vertebral fractures on health-related quality of life (HRQOL) in postmenopausal women with osteoporosis and to characterize the effect of prevalent vertebral fractures on HRQOL with respect to number, location, severity, and adjacency. Methods. Participants were a subset of women (n = 1,395, mean age 68.5 years) from the Multiple Outcomes of Raloxifene Evaluation trial who had low bone mineral density and/or prevalent vertebral fractures. Vertebral fractures were measured by radiography at baseline, 2 years, and 3 years. HRQOL was assessed using the Osteoporosis Assessment Questionnaire (OPAQ), a validated disease-targeted instrument, at baseline and annually for 3 years. Results. Both prevalent and incident radiographic vertebral fractures were associated with decreased HRQOL. At baseline, women with a prevalent vertebral fracture had significantly lower OPAQ scores on physical function, emotional status, clinical symptoms, and overall HRQOL compared with women without a prevalent fracture (all P < 0.01). HRQOL scores were lower with each subsequent fracture. The effect of prevalent vertebral fracture was dependent on the location within the spine and was strongest in the lumbar region (L1-L4). Incident vertebral fractures significantly decreased OPAQ scores on physical function, emotional status, clinical symptoms, and overall HRQOL (all P < 0.001). Conclusion. Our findings demonstrate the importance of treating postmenopausal women who have prevalent vertebral fractures to prevent further decreases in HRQOL associated with subsequent incident vertebral fracture. C1 OMC Clin Res Ctr, Beverly Hills, CA 90211 USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Greater Los Angeles VA Hlth Syst, Los Angeles, CA 90048 USA. Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. RP Silverman, SL (reprint author), OMC Clin Res Ctr, 8641 Wilshire Blvd,Suite 310, Beverly Hills, CA 90211 USA. NR 26 TC 194 Z9 197 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2001 VL 44 IS 11 BP 2611 EP 2619 DI 10.1002/1529-0131(200111)44:11<2611::AID-ART441>3.0.CO;2-N PG 9 WC Rheumatology SC Rheumatology GA 498CC UT WOS:000172491400018 PM 11710717 ER PT J AU McNally, RJ Otto, MW Hornig, CD AF McNally, RJ Otto, MW Hornig, CD TI The voice of emotional memory: content-filtered speech in panic disorder, social phobia, and major depressive disorder SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article ID THIN SLICES; BEHAVIOR AB We asked patients with either panic disorder, social phobia, or major depressive disorder and healthy control participants to describe their most frightening experience and to describe an emotionally neutral experience. Both fear and neutral autobiographical memories were audiotaped and processed through a low-pass filter that eliminated frequencies above 400 Hz, thereby abolishing semantic content but leaving paralinguistic aspects like rate, pitch, and loudness intact, and these convey emotional cues. Raters blind to content and diagnosis rated the content-filtered speech clips on emotional dimensions. The results revealed that content-filtered fear memories received significantly higher ratings on anxious, aroused, and dominant (but not sad or negative) scales than did content-filtered neutral memories, irrespective of the diagnostic status of the speaker. Content-filtered speech appears promising as an on-line probe of emotional processing during accessing of autobiographical memories. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP McNally, RJ (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. FU NIMH NIH HHS [MH51927] NR 14 TC 8 Z9 8 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD NOV PY 2001 VL 39 IS 11 BP 1329 EP 1337 DI 10.1016/S0005-7967(00)00100-5 PG 9 WC Psychology, Clinical SC Psychology GA 483PA UT WOS:000171642400005 PM 11686267 ER PT J AU Rauch, SL Dougherty, DD Cosgrove, GR Cassem, EH Alpert, NM Price, BH Nierenberg, AA Mayberg, HS Baer, L Jenike, MA Fischman, AJ AF Rauch, SL Dougherty, DD Cosgrove, GR Cassem, EH Alpert, NM Price, BH Nierenberg, AA Mayberg, HS Baer, L Jenike, MA Fischman, AJ TI Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for obsessive compulsive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE neurosurgery; positron emission tomography; posterior cingulate cortex; anxiety; neuroimaging; treatment ID POSITRON-EMISSION-TOMOGRAPHY; CINGULATE CORTEX; RETROSPLENIAL CORTEX; TEMPORAL LOBECTOMY; RHESUS-MONKEY; HUMAN BRAIN; DEPRESSION; EMOTION; PET; PHARMACOTHERAPY AB Background: As interventions for severe, treatment-refractory obsessive compulsive disorder (OCD), neurosurgical procedures are associated with only modest efficacy. The purpose of this study was to identify cerebral metabolic correlates as potential predictors of treatment response to anterior cingulotomy for OCD. Methods: Clinical data were analyzed in the context of a retrospective design. Subjects were 11 patients who underwent stereotactic anterior cingulotomy for OCD. Symptom severity was measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and at approximately 6 months postoperative. Preoperative F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) data were available. Statistical parametric mapping methods were used to identify loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in Y-BOCS scores. Results: One locus within right posterior cingulate cortex was identified, where preoperative metabolism was significantly correlated with improvement in OCD symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at that locus were associated with better postoperative outcome. Conclusions: A possible predictor of treatment response was identified for patients with OCD undergoing anterior cingulotomy. Further research, utilizing a prospective design, is indicated to determine the validity and reliability of this finding. If confirmed, an index for noninvasively predicting response to cingulotomy for OCD would be of great value. (C) 2001 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp East, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. Harvard Med Sch, Boston, MA USA. McLean Hosp, Dept Neurol, Belmont, MA USA. Univ Toronto, Rotman Res Inst, Dept Psychiat, Toronto, ON, Canada. Univ Toronto, Rotman Res Inst, Dept Neurol, Toronto, ON, Canada. RP Rauch, SL (reprint author), Massachusetts Gen Hosp East, Dept Psychiat, 13th St,Bldg 149,Room 9130, Charlestown, MA 02129 USA. FU NIMH NIH HHS [R01 MH50275, R01 MH60219] NR 46 TC 89 Z9 94 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2001 VL 50 IS 9 BP 659 EP 667 DI 10.1016/S0006-3223(01)01188-X PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 490DL UT WOS:000172035100002 PM 11704072 ER PT J AU Kurtz, SM Muratoglu, OK Buchanan, FJ Currier, B Gsell, R Shen, FW Yau, SS AF Kurtz, SM Muratoglu, OK Buchanan, FJ Currier, B Gsell, R Shen, FW Yau, SS TI Interlaboratory studies to determine optimal analytical methods for measuring the oxidation index of UHMWPE SO BIOMATERIALS LA English DT Article DE ultra-high molecular weight polyethylene; UHMWPE; oxidation; degradation; Fourier transform infrared spectroscopy; FTIR ID MOLECULAR-WEIGHT POLYETHYLENE; INFRARED SPECTROMETRY; STERILIZATION; DEGRADATION; IMPLANTS AB Fourier transform infrared spectroscopy has emerged as the technique of choice for the quantification of oxidation in ultra-high molecular weight polyethylene used in orthopedic implants. We initiated interlaboratory studies to determine the method of normalization, hence quantification, that provided the highest level of reproducibility across multiple institutions. The goal of this research was to identify optimal normalization methods that minimize the experimental uncertainties associated with interlaboratory reproducibility and intralaboratory repeatability of oxidation index measurements. Test samples were prepared from GUR 4150 HP, gamma irradiated in air, and had a shelf age of two years. Samples were analyzed according to ten oxidation index test methods during two interlaboratory studies, which were conducted in accordance with ASTM E691. Variations in reproducibility and repeatability were evaluated using analysis of variance (ANOVA). The basis of the test methods (peak area-based vs. peak height-based), as well as the normalization method, were both found to be associated with significant differences in reproducibility (p = 0.0006 and p < 0.0001, respectively). Normalization techniques based on the 1370 and 2022 cm(-1) peaks areas were found to be the most reproducible methods, and were associated with mean interlaboratory uncertainties of 16.5% and 24.2%, respectively. Repeatability of the test methods was not sensitive to the normalization technique; the mean intralaboratory repeatability for all of oxidation index measurements was found to be 10.2%. The results of this interlaboratory research will be a useful basis for the development of a new oxidation index standard for the orthopedics community. (C) 2001 Published by Elsevier Science Ltd. C1 Exponent Inc, Philadelphia, PA 19103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Queens Univ Belfast, Belfast, Antrim, North Ireland. Dartmouth Coll, Hanover, NH USA. Zimmer Inc, Warsaw, IN USA. Orthoped Hosp, Los Angeles, CA 90007 USA. Howmedica Osteon Corp, Rutherford, NJ USA. RP Kurtz, SM (reprint author), Exponent Inc, 2300 Chestnut St,Suite 150, Philadelphia, PA 19103 USA. OI Currier, Barbara/0000-0003-3273-225X NR 24 TC 33 Z9 33 U1 0 U2 6 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 NOV PY 2001 VL 22 IS 21 BP 2875 EP 2881 DI 10.1016/S0142-9612(01)00033-3 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 469MT UT WOS:000170820000007 PM 11561893 ER PT J AU Goldstein, AS Amory, JK Martin, SM Vernon, C Matsumoto, A Yager, P AF Goldstein, AS Amory, JK Martin, SM Vernon, C Matsumoto, A Yager, P TI Testosterone delivery using glutamide-based complex high axial ratio nficrostructures SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID IN-VITRO; MICROSTRUCTURES; MICROSPHERES; DEGRADATION; UNDECANOATE AB Complex high axial ratio microstructures (CHARMs) were evaluated for delivery of testosterone in vivo. Methods to incorporate testosterone included noncovalent mixing and covalent attachment of testosterone to the lipid to form a prodrug monomer. When prepared by covalent attachment, testosterone-loaded CHARMs were resistant to in vitro spontaneous hydrolysis; when injected into rats, testosterone was released with biphasic kinetics consisting of a burst followed by a much slower phase. Some CHARM material associated with testosterone persisted at the site of injection for at least 9 days. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Gen Internal Med Sect, Seattle, WA 98108 USA. Univ Washington, Dept Chem, Seattle, WA 98195 USA. Univ Washington, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Dept Bioengn, Mol Bioengn Program, Seattle, WA 98195 USA. RP Yager, P (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 32 TC 20 Z9 22 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV PY 2001 VL 9 IS 11 BP 2819 EP 2825 DI 10.1016/S0968-0896(01)00149-3 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 485KF UT WOS:000171753000008 PM 11597462 ER PT J AU Hsu, JH Shi, YJ Krajewski, S Renner, S Fisher, M Reed, JC Franke, TF Lichtenstein, A AF Hsu, JH Shi, YJ Krajewski, S Renner, S Fisher, M Reed, JC Franke, TF Lichtenstein, A TI The AKT kinase is activated in multiple myeloma tumor cells SO BLOOD LA English DT Article ID INDUCED APOPTOSIS; GROWTH-FACTORS; PLASMA-CELLS AB Immunohistochemistry (IHC) was performed on archived bone marrow (BM) with a phosphospecific anti-AKT antibody. IHC on 26 BM biopsies from patients with multiple myeloma (MM) demonstrated phospho-AKT staining of malignant plasma cells in a cell membrane-specific pattern, whereas nonmalignant hematopoietic cells did not stain. Preabsorption of the antibody with phosphorylated AKT peptide, but not nonphosphorylated peptide, abrogated staining. Frequency of plasma cell staining in BMs of patients with stage I or smoldering MM was significantly less than that of stage III MM marrows. Plasma cells in 10 patients with monoclonal gammopathy of undetermined significance were not stained by the antibody. To investigate the significance of AKT activation, 2 cell lines initiated from cultures of primary MM cells were also studied. Both demonstrated constitutive AKT activation. Interruption of AKT activation and activity, achieved by either exposure to wortmannin or by ectopic expression of a dominant negative AKT mutant, resulted in inhibition of MM cell growth in vitro. These results indicate that activation of the AKT kinase is a characteristic of MM cells and suggest that AKT activity is important for MM cell expansion. (C) 2001 by The American Society of Hematology. C1 W Los Angeles Vet Adm Med Ctr, Dept Pathol & Med, Los Angeles, CA USA. Jonsson Comprehens Canc Ctr, Los Angeles, CA 90034 USA. Burnham Inst, La Jolla, CA 92037 USA. Columbia Univ, Dept Pharmacol, New York, NY USA. RP Lichtenstein, A (reprint author), VA W LA Hosp, W111H,11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA69381]; NINDS NIH HHS [NS3621] NR 14 TC 136 Z9 138 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2001 VL 98 IS 9 BP 2853 EP 2855 DI 10.1182/blood.V98.9.2853 PG 3 WC Hematology SC Hematology GA 487CK UT WOS:000171855900036 PM 11675360 ER PT J AU Bliziotes, MM Eshleman, AJ Zhang, XW Wiren, KM AF Bliziotes, MM Eshleman, AJ Zhang, XW Wiren, KM TI Neurotransmitter action in osteoblasts: Expression of a functional system for serotonin receptor activation and reuptake SO BONE LA English DT Article DE bone; osteoblast; neurotransmitter; serotonin; receptor; transporter ID VASOACTIVE INTESTINAL POLYPEPTIDE; PROTEIN-KINASE-C; IMMUNOREACTIVE NERVES; RAT OSTEOBLASTS; ANTIPEPTIDE ANTIBODIES; GLUTAMATE RECEPTORS; 5-HT1A RECEPTOR; BINDING PROTEIN; BONE-RESORPTION; EMBRYONIC MOUSE AB Neurotransmitter regulation of bone metabolism has been the subject of increasing interest and investigation. Because serotonin (5-HT) plays a role as a regulator of craniofacial morphogenesis, we investigated the expression and function of 5-HT receptors and the 5-HT transporter (5-HTT) in bone. Primary cultures of rat osteoblasts (rOB) and a variety of clonal osteoblastic cell lines, including ROS 17/2.8, UMR 106-H5, and Pyla, showed mRNA expression for 5-HTT as well as the 5-HT1A, 5-HT1D, 5-HT2A, and 5-HT2B, receptors by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Protein expression of the 5-HT1A, 5-HT2A, and 5-HT2B receptors was confirmed by immunoblot. 5-HTT binding sites were assessed in ROS 17/2.8 and UMR 106-H5 cells by binding of the stable cocaine analog [I-125]RTI-55, which showed a relatively high density of nanomolar affinity binding sites. Imipramine and fluoxetine, antagonists with specificity for 5-HTT, showed the highest potency to antagonize [I-125]RTI-55 binding in ROS and UMR cells. GBR-12935, a relatively selective dopamine transporter antagonist, had a much lower potency, as did desipramine, a selective norepinephrine transporter antagonist. The maximal [H-3]5-HT uptake rate in ROS cells was 110 pmol/10 min per well, with a K-m value of 1.13 mu mol/L. Imipramine and fluoxetine inhibited specific [H-3]5-HT uptake with IC50 values in the nanomolar range. In normal differentiating rOB cultures, 5-HTT functional activity was observed initially at day 25, and activity increased almost eightfold by day 31. In mature rOB cultures, the estimated density of [I-125]RTI-55 binding sites was 600 fmol/mg protein. Functional downregulation of transporter activity was assessed after PMA treatment, which caused a significant 40% reduction in the maximal uptake rate of [H-3]5-HT, an effect that was prevented by pretreatment with staurosporine. The affinity of 5-HT for the transporter was significantly increased following PMA treatment. We assessed the functional significance of expression of the 5-HT receptors by investigating the interaction between 5-HT and parathyroid hormone (PTH) signaling. 5-HT potentiates the PTH-induced increase in AP-1 activity in UMR cells. These results demonstrate that osteoblastic cells express a functional serotonin system, with mechanisms for responding to and regulating uptake of 5-HT. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR USA. RP Bliziotes, MM (reprint author), Dept Vet Affairs Med Ctr, P3-3710 SW Vet Hosp Rd, Portland, OR 97201 USA. OI Wiren, Kristine/0000-0002-6159-4450 FU NIDDK NIH HHS [DK54415] NR 58 TC 118 Z9 127 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD NOV PY 2001 VL 29 IS 5 BP 477 EP 486 DI 10.1016/S8756-3282(01)00593-2 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 492ET UT WOS:000172156000013 PM 11704501 ER PT J AU Caplan, D AF Caplan, D TI Points regarding the functional neuroanatomy of syntactic processing: A response to Zurif (2001) SO BRAIN AND LANGUAGE LA English DT Editorial Material ID SENTENCE COMPREHENSION; APHASIA C1 Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. NR 12 TC 5 Z9 5 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD NOV PY 2001 VL 79 IS 2 BP 329 EP 332 DI 10.1006/brln.2001.2488 PG 4 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 496XW UT WOS:000172424500009 ER PT J AU Bunnell, CA Supko, JG Eder, JP Clark, JW Lynch, TJ Kufe, DW Shulman, LN AF Bunnell, CA Supko, JG Eder, JP Clark, JW Lynch, TJ Kufe, DW Shulman, LN TI Phase I clinical trial of 7-cyanoquinocarcinol (DX-52-1) in adult patients with refractory solid malignancies SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE DX-52-1; quinocarmycin; cancer; chemotherapy; clinical trials; pharmacokinetics; human ID LIQUID-CHROMATOGRAPHY; ANTITUMOR-ACTIVITY; HUMAN PLASMA; QUINOCARCIN; KW2152; CLEAVAGE; MICE; DNA AB Purpose: A phase I study of the antitumor antibiotic 7-cyanoquinocarcinol, DX-52-1, was conducted in patients with refractory solid malignancies. This study sought to determine the maximum tolerated dose and principal toxicities of this agent and to characterize its pharmacokinetic behavior. Methods: Patients were required to have adequate bone marrow, renal and hepatic function. DX-52-1 was administered by i.v. continuous infusion over a 6-h period each week for four consecutive weeks followed by a 2-week rest period, which constituted one cycle of treatment. Results: Initial dose levels were 3, 6, and 10 mg/m(2). An intermediate dose level of 8 mg/m(2) was added after acceptable toxicity was observed at the 6 mg/m dose level, but doselimiting toxicities, including life-threatening ones, were seen at the 10 mg/m(2) dose level in all three patients. The maximum tolerated dose (MTD) was subsequently determined to be 6 mg/m(2). Because a clear pattern of toxicities was not initially evident, a larger than usual number of additional patients (16) were enrolled at the MTD to better distinguish toxicities due to the study drug from those secondary to the patients' underlying malignancies. Even at the MTD, the drug was poorly tolerated, with gastrointestinal toxicities (abdominal pain, nausea, vomiting and increased liver function tests) predominating and dose-limiting. Pharmacokinetic studies revealed that the mean maximum plasma concentration of DX-52-1 in patients evaluated at the MTD (138.8 +/- 59.3 ng/ml, n = 19) was considerably lower than the concentrations required for cytostatic or cytotoxic activity against sensitive human tumor cell lines in vitro. Further, the weekly dose intensity of the most efficacious treatment schedule identified during in vivo antitumor efficacy studies was 60 times greater than the 6 mg/m(2) weekly dose tolerated by cancer patients. None of the 33 patients participating in this study, including the 22 patients evaluated at the MTD, had any response to treatment. Conclusion: Given the poor tolerability, the inability to achieve drug levels necessary to inhibit in vitro or in vivo tumor growth, and the lack of any responses in our study, DX-52-1, as given by this schedule, does not appear to warrant further investigation in phase II studies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. RP Bunnell, CA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [U01 CA62490] NR 28 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2001 VL 48 IS 5 BP 347 EP 355 DI 10.1007/s002800100319 PG 9 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 498BF UT WOS:000172489400002 PM 11761451 ER PT J AU Willers, H McCarthy, EE Hubbe, P Dahm-Daphi, J Powell, SN AF Willers, H McCarthy, EE Hubbe, P Dahm-Daphi, J Powell, SN TI Homologous recombination in extrachromosomal plasmid substrates is not suppressed by p53 SO CARCINOGENESIS LA English DT Article ID DOUBLE-STRAND BREAKS; CELL-CYCLE REGULATION; WILD-TYPE P53; MAMMALIAN-CELLS; GENE CONVERSION; DNA-REPAIR; MUTANT P53; SITE; DISSOCIATION; CHROMOSOMES AB We and others reported previously that the tumor suppressor p53 down-regulates spontaneous homologous recombination in chromosomally integrating plasmid substrates, but how p53 affects homology-dependent repair of DNA double-strand breaks has not been established. Furthermore, it has been hypothesized that p53 may suppress homologous recombination by direct interaction with recombination intermediates, but it is not known whether p53 directly acts on extrachromosomal plasmid substrates. In the present study, we asked whether p53 can suppress extrachromosomal spontaneous and double-strand break-induced homologous recombination. A plasmid shuttle assay was employed utilizing episomally replicating substrates, which carried mutated tandem repeats of a CAT reporter gene. Spontaneous homologous recombination and homology-dependent repair of double-strand breaks induced by the I-SceI nuclease led to reconstitution of the reporter. Extrachromosomal homologous recombination was found to proceed independently of the p53 status of isogenic mouse fibroblast lines, contrasting the p53-mediated suppression of chromosomal recombination. The lack of p53 effect applied not only to the dominating single-strand annealing pathway, which is Rad51-independent, but also to Rad51-dependent gene conversion events. Comparison of homologous and non-homologous recombination frequencies revealed similar contributions to the repair of I-SceI-induced breaks irrespective of p53 status. Our results are consistent with a model in which the regulation of homologous recombination by p53 is restricted to the highly ordered chromosomal chromatin structure. These data may serve as a cautionary note for future investigations using solely extrachromosomal model systems to address DNA repair in intact cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Lab Mol & Cellular Radiat Biol, Charlestown, MA 02129 USA. Univ Hamburg, Dept Radiat Oncol, Expt Radiat Oncol Lab, D-20246 Hamburg, Germany. RP Powell, SN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,Lab Mol & Cellular Radiat Biol, Charlestown, MA 02129 USA. NR 37 TC 22 Z9 23 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2001 VL 22 IS 11 BP 1757 EP 1763 DI 10.1093/carcin/22.11.1757 PG 7 WC Oncology SC Oncology GA 493AD UT WOS:000172199100003 PM 11698336 ER PT J AU Washington, B Butler, K Doye, AA Jang, M Hajjar, RJ Gwathmey, JK AF Washington, B Butler, K Doye, AA Jang, M Hajjar, RJ Gwathmey, JK TI Heart function challenged with beta-receptor agonism or antagonism in a heart failure model SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Article DE heart failure; beta-blocker; isoproterenol turkey ID HUMAN VENTRICULAR MYOCARDIUM; FORCE-FREQUENCY-RELATIONSHIP; DILATED CARDIOMYOPATHY; SHORT-TERM; ADRENOCEPTORS; CARTEOLOL; BLOCKADE; DYSFUNCTION; ATPASE AB We have shown that chronic treatment with carteolol, a non-selective beta-adrenergic receptor antagonist, improved left ventricular (LV) function and survival in an avian model of dilated cardiomyopathy (DCM). The aim of the present study was to compare ex vivo heart function with and without beta-agonist and antagonist challenge. We investigated whether intracoronary infusion of a beta-blocker, carteolol or beta-agonist, isoproterenol decreased contractility. In the DCM group, isoproterenol resulted in a significantly greater increase in heart rate (71% vs. 28% compared to control hearts). To investigate the mechanism for the increase in heart rate, we exposed spontaneously beating neonatal cardiomyocytes to serum immunoglobulin (IgG) isolated from DCM animals. Serum IgG resulted in a significant increase in spontaneous beating rate in neonatal rat cardiomyocytes that was blocked by pre-treatment with a beta-blocker. Carteolol challenge did not significantly change heart rate but did significantly increase LV peak pressure in DCM hearts (62%) while coronary artery flow remained unchanged (2.7 +/- 0.1 vs 2.7 +/- 0.5 ml/min/g). These results show that 1) beta-receptor stimulation results in a greater tachycardic response in DCM animals, and 2) carteolo challenge improves myocardial contractility in hearts from DCM animals independent of heart rate or changes in coronary artery flow. C1 Tennessee State Univ, Dept Biol Sci, Nashville, TN 37209 USA. Morehouse Sch Med, Dept Physiol, Atlanta, GA 30310 USA. Morehouse Sch Med, Dept Surg, Atlanta, GA 30310 USA. Boston Univ, Sch Med, Cambridge, MA 02138 USA. Gwathmey Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Charlestown, MA 02125 USA. RP Washington, B (reprint author), Tennessee State Univ, Dept Biol Sci, Nashville, TN 37209 USA. FU NCRR NIH HHS [RR11808]; NHLBI NIH HHS [HL 57623, R43-IHL52249, HL 50356]; PHS HHS [R44-52249] NR 30 TC 2 Z9 2 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD NOV PY 2001 VL 15 IS 6 BP 479 EP 486 DI 10.1023/A:1013755402109 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 512JQ UT WOS:000173321600002 PM 11916356 ER PT J AU Gaglia, JL Mattoo, A Greenfield, EA Freeman, GJ Kuchroo, VK AF Gaglia, JL Mattoo, A Greenfield, EA Freeman, GJ Kuchroo, VK TI Characterization of endogenous Chinese hamster ovary cell surface molecules that mediate T cell costimulation SO CELLULAR IMMUNOLOGY LA English DT Article DE costimulatory molecules; T lymphocytes; spleen; rodent ID INTERCELLULAR-ADHESION MOLECULE-1; COMPLEMENT REGULATORY PROTEIN; UROKINASE-RECEPTOR; PLASMINOGEN-ACTIVATOR; CD28 COSTIMULATION; INVARIANT CHAIN; MOUSE; EXPRESSION; ANTIBODY; ANTIGEN AB Chinese hamster ovary (CHO) cells are commonly used in the generation of transfectants for use in in vitro costimulation assays. However, we have noted that nontransfected CHO cells can themselves provide a low-level B7/CD28 independent costimulatory signal for CD3-mediated murine T cell activation and IL-2 production. This study set out to identify those molecules that contribute to this CHO-dependent costimulatory activity. We describe a CHO subline capable of delivering potent CD28-independent costimulation to murine T cells and the generation of monoclonal antibodies against these CHO cells that inhibited this costimulatory activity. These blocking antibodies do not affect CHO cell-independent costimulation or bind mouse cells, suggesting an effect mediated by their target molecules on the costimulatory competent CHO cells. Immunoprecipitation and expression cloning revealed that these antibodies bound the hamster homologues of Crry (CD21/35), CD44, CD54 (ICAM-1), CD63, CD87, CD147, and an 80- to 90-kDa protein which could not be cloned. Expression of these hamster genes on COS cells demonstrated that hamster CD54 was able to costimulate both CD3-mediated IL-2 secretion and T cell proliferation by naive murine T cells independent of the other molecules identified. (C) 2001 Elsevier Science (USA). C1 Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kuchroo, VK (reprint author), Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, 75 Francis St, Boston, MA 02115 USA. OI Gaglia, Jason/0000-0003-2904-312X FU NCI NIH HHS [CA84500]; NIAID NIH HHS [P01AI39671-01A1, AI39671, AI41584]; NINDS NIH HHS [R01NS35685, R01NS30843] NR 57 TC 11 Z9 11 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV 1 PY 2001 VL 213 IS 2 BP 83 EP 93 DI 10.1006/cimm.2001.1867 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 524AH UT WOS:000173989400001 PM 11831870 ER PT J AU Barr, RG Cooper, DM Speizer, FE Drazen, JM Camargo, CA AF Barr, RG Cooper, DM Speizer, FE Drazen, JM Camargo, CA TI beta(2)-Adrenoceptor polymorphism and body mass index are associated with adult-onset asthma in sedentary but not active women SO CHEST LA English DT Article DE asthma; beta(2)-adrenoceptor polymorphism; gene/environment interaction; obesity; physical activity ID AIRWAY SMOOTH-MUSCLE; GENETIC POLYMORPHISMS; PHYSICAL-ACTIVITY; RECEPTOR; POPULATION; ADRENOCEPTOR; ALBUTEROL; HISTORY; WEIGHT AB Study objective: beta (2)-Adrenoceptor Gly16 polymorphism has been associated with asthma severity and beta (2)-adrenoceptor receptor downregulation, but not with the diagnosis of asthma. Glu27 polymorphism may limit beta (2)-adrenoceptor downregulation and predict body mass index (BMI), particularly among sedentary persons. In addition, BMI predicts asthma. We hypothesized that these DNA sequence variants predict adult-onset asthma only in sedentary women. Design: Nested case-control study. Setting: Nurses' Health Study, a large, prospective cohort study with participants throughout the United States. Participants: Among lifelong nonsmokers, 171 women with adult-onset, medication-requiring asthma and 137 age-matched control subjects. Measurements: Physical activity and BMI were self-reported by previously validated questionnaire items. Genomic DNA was obtained from buccal brushings collected via first-class mail. Results: Of 76 sedentary women, the adjusted odds ratios of Gly16 allele were 7.4 (p=0.047) for asthma and 13.8 (p=0.02) for steroid-requiring asthma. No similar associations were observed among 232 active women (p=0.91). Sedentary individuals with both Gly16 and Glu27 alleles had a less elevated risk for asthma. BMI was associated with asthma and Glu27 allele among sedentary women. Conclusion: This exploratory analysis suggests an important gene/environment interaction for asthma involving physical activity level. Further study in larger populations is warranted to confirm if sedentary lifestyle unmasks a genetic risk for asthma. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Pulm & Crit Care Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Atlantic Hlth Syst, Childrens Med Ctr, Resp Ctr Children, Morristown, NJ USA. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Drazen, Jeffrey/E-5841-2012 FU BHP HRSA HHS [PE-11001]; NCI NIH HHS [CA-87969]; NHLBI NIH HHS [HL-03533, HL-07427] NR 30 TC 27 Z9 28 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2001 VL 120 IS 5 BP 1474 EP 1479 DI 10.1378/chest.120.5.1474 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 494GW UT WOS:000172274300014 PM 11713122 ER PT J AU Roberts, DH Lepore, JJ Maroo, A Semigran, MJ Ginns, LC AF Roberts, DH Lepore, JJ Maroo, A Semigran, MJ Ginns, LC TI Oxygen therapy improves cardiac index and pulmonary vascular resistance in patients with pulmonary hypertension SO CHEST LA English DT Article; Proceedings Paper CT CHEST 2000 Meeting CY OCT 25, 2000 CL SAN FRANCISCO, CALIFORNIA SP CHEST DE oxygen therapy; pulmonary; hypertension; pulmonary vasodilatation ID SMOOTH-MUSCLE CELLS; VASOCONSTRICTION; PROSTACYCLIN; DISEASE; CIRCULATION; GENE; SITE AB Study objectives: We tested the hypothesis that breathing 100% oxygen could result in selective pulmonary vasodilatation in patients with pulmonary hypertension, including those patients who would not meet current Health Care Finance Administration guidelines for long-term oxygen therapy. Design, setting, and patients: From 1996 to 1999, 23 adult patients (mean +/- SEM age, 51 +/-4 years) with pulmonary arterial hypertension without left-heart failure underwent cardiac catheterization in a university teaching hospital while breathing air and then 100% oxygen. Measurements and results: Treatment with 100% oxygen increased arterial oxygen saturation (91 +/-1% to 99 +/-0.1%, p<0.05) and Pao(2) (643 to 309 +/- 28 min Hg, p<0.05). Treatment with 100% oxygen also decreased mean pulmonary artery pressure (563 to 53 +/-2 mm Hg, p<0.05) and increased cardiac index (2.10.1 to 2.5 +/-0.2 L/min/m(2), p<0.05). Calculated mean pulmonary vascular resistance (PVR) decreased from 14.11.4 to 10.6 +/-1.0 Wood units (p<0.05). Vasodilatation with 100% oxygen occurred preferentially in the pulmonary circulation (PVR/systemic vascular resistance, 0.530.04 to 0.48 +/-0.03; p<0.05). The magnitude of the PVR response to oxygen therapy was correlated only with decreasing patient age (r=0.45, p<0.05). Conclusions: Treatment with 100% oxygen is a selective pulmonary vasodilator in patients with pulmonary hypertension, regardless of primary diagnosis, baseline oxygenation, or right ventricular function. Development of disease-specific oxygen prescription guidelines warrants consideration. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ginns, LC (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Bigelow 806,Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-04021] NR 32 TC 44 Z9 47 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2001 VL 120 IS 5 BP 1547 EP 1555 DI 10.1378/chest.120.5.1547 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 494GW UT WOS:000172274300025 PM 11713133 ER PT J AU Thompson, BT Hayden, D Matthay, MA Brower, R Parsons, PE AF Thompson, BT Hayden, D Matthay, MA Brower, R Parsons, PE TI Clinicians' approaches to mechanical ventilation in acute lung injury and ARDS SO CHEST LA English DT Article DE acute lung injury; ARDS; mechanical ventilation ID RESPIRATORY-DISTRESS SYNDROME; MORTALITY; STRATEGY; TRIAL AB Study objectives: To examine clinicians' approaches to mechanical ventilation in patients with acute lung injury (ALI; Pao(2)/fraction of inspired oxygen [FIO2] less than or equal to 300) and compare ventilator settings in patients with ARDS (Pao(2)/FIO2 less than or equal to 200) to settings in patients with milder oxygenation impairment (Pao(2)/FIO2 of 201 to 300). Design: Retrospective analysis of baseline data from prospective randomized trials conducted by the National Institutes of Health ARDS Network between 1996 and 1999. Setting: Ten clinical centers comprising 24 hospitals and 74 medical and surgical ICUs of the ARDS Network. Measurements and results: The most common mode of mechanical ventilation in both groups was volume-assist control (56%). Synchronized intermittent mandatory ventilation (SIMV) or SIMV with pressure support was used more often in patients with Pao(2)/FIO2 of 201 to 300 than in patients with ARDS. The use of pressure-control ventilation was uncommon (10% overall), as was the use of permissive hypercapnia (6% of patients with ARDS and 3% of patients with Pao(2)/FIO2 of 201 to 300). The mean +/- SD tidal volume was 10.3 +/- 2 mL/kg of predicted body weight or 8.6 +/- 2 mL/kg of measured weight for patients with ARDS, and was not significantly different for patients with Pao(2)/FIO2 of 201 to 300. Plateau pressures (Pplats) were lower in the Pao(2)/FIO2 of 201 to 300 group (27 +/- 7 vs 31 +/- 8 for the ARDS group; p = 0.0003) and were > 35 cm H2O in 26% of patients. Seventy-eight percent of patients with ARDS received less than or equal to 10 cm H2O of positive end-expiratory pressure. Conclusions: Physicians in ARDS Network centers caring for patients early in the course of ALI/ARDS used volume-targeted ventilation and selected tidal volumes that resulted in Pplats generally < 35 cm H2O. The average tidal volume was similar for patients with ARDS vs those with milder oxygenation deficits. C1 Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA. Fletcher Allen Hlth Care, Pulm & Crit Care Unit, Burlington, VT USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [N01-HR 46054-64] NR 15 TC 58 Z9 61 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2001 VL 120 IS 5 BP 1622 EP 1627 DI 10.1378/chest.120.5.1622 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 494GW UT WOS:000172274300036 PM 11713144 ER PT J AU Vonderheide, RH Anderson, KS Hahn, WC Butler, MO Schultze, JL Nadler, LM AF Vonderheide, RH Anderson, KS Hahn, WC Butler, MO Schultze, JL Nadler, LM TI Characterization of HLA-A3-restricted cytotoxic T lymphocytes reactive against the widely expressed tumor antigen telomerase SO CLINICAL CANCER RESEARCH LA English DT Article ID MELANOMA PATIENTS; CELLS; CANCER; MOUSE; IMMUNOTHERAPY; DETERMINANTS; INHIBITION; REGRESSION; TISSUES AB Purpose: We have reported previously that the telomerase catalytic subunit, human telomerase reverse transcriptase (hTERT), is a widely expressed tumor-associated antigen recognized by CTLs. A nine-amino acid peptide derived from hTERT binds strongly to HLA-A2 antigen and elicits CTL responses against a broad panel of hTERT(+) tumors (but not hTERT(+) hematopoietic progenitor cells). The applicability of hTERT as a potential target for anticancer immunotherapy would be widened by the identification of epitopes restricted to other common HLA alleles, such as HLA-A3 antigen. Experimental Design: Using a method of epitope deduction, HLA-A3-restricted peptide epitopes were screened from hTERT and tested for immunogenicity in a human in vitro T-cell system. Results: The hTERT peptide K973 was used to generate specific CD8(+) CTLs from HLA-A3(+) cancer patients and healthy individuals. These CTLs lysed hTERT(+) tumors from multiple histologies in an MHC-restricted fashion, suggesting that the epitope is naturally processed and presented by tumors. In contrast, highly enriched HLA-A3(+) CD34(+) peripheral blood progenitor cells or activated T cells were not lysed. Conclusion: Given the expression of HLA-A2 and HLA-A3 antigen in the general population, these findings extend the potential applicability of hTERT as a therapeutic target to > 60 % of all cancer patients. The characterization of hTERT as a polyepitope, polyallelic tumor-associated antigen may provide an approach for circumventing therapy-induced resistance potentially mediated by antigenic- and allelic-loss tumor escape mutants. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Vonderheide, RH (reprint author), Univ Penn, Sch Med, Abramson Family Canc Res Inst, 551 BRB2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [1K08-CA-88444-01, P01-CA-66996] NR 35 TC 88 Z9 95 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 BP 3343 EP 3348 PG 6 WC Oncology SC Oncology GA 491JX UT WOS:000172106200006 PM 11705846 ER PT J AU Streit, M Stephen, AE Hawighorst, T Lange-Asschenfeldt, B Brown, LF Vacanti, JP Detmar, A AF Streit, M Stephen, AE Hawighorst, T Lange-Asschenfeldt, B Brown, LF Vacanti, JP Detmar, A TI Systemic inhibition of tumor growth and angiogenesis by thrombospondin-2 using cell-based anti-angiogenic gene therapy. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 38 BP 3661S EP 3661S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800039 ER PT J AU Soker, S Schuch, G Nomi, M Connors, S Proper, J Clark, JW Kufe, DW Folkman, JM Eder, JP AF Soker, S Schuch, G Nomi, M Connors, S Proper, J Clark, JW Kufe, DW Folkman, JM Eder, JP TI Circulating endothelial progenitor cells in cancer diagnosis and therapy. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 60 BP 3665S EP 3665S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800061 ER PT J AU Wulfkuhle, JD McLean, K Sgroi, D Sahin, A Petricoin, E Steeg, P AF Wulfkuhle, JD McLean, K Sgroi, D Sahin, A Petricoin, E Steeg, P TI Proteomic analysis of breast cancer progression. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 NIH, NCI, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 153 BP 3684S EP 3684S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800152 ER PT J AU Forouzesh, B Hidalgo, M Denis, L Schwartz, G Hammond, L Monroe, P Guzman, C Lazaro, LL Supko, J Jimeno, J Rowinsky, EK AF Forouzesh, B Hidalgo, M Denis, L Schwartz, G Hammond, L Monroe, P Guzman, C Lazaro, LL Supko, J Jimeno, J Rowinsky, EK TI Phase I and pharmacokinetic study of the marine-derived DNA minor groove binder ET-743 on a weekly x3 every-4-week schedule in patients with advanced solid malignancies. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. Brooke Army Med Ctr, San Antonio, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. PharmaMar Pharmaceut Inc, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 209 BP 3694S EP 3695S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800206 ER PT J AU Puchalski, TA Eder, JP Ryan, DP Clark, JW Castellana, W Garcia-Carbonero, R Kufe, DW Supko, JG AF Puchalski, TA Eder, JP Ryan, DP Clark, JW Castellana, W Garcia-Carbonero, R Kufe, DW Supko, JG TI A phase I trial of sarcosinamide nitrosourea in adult patients with solid tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 278 BP 3709S EP 3709S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800274 ER PT J AU Agata, N Umanoff, H Milhollen, M Fram, R Kufe, D Kharbanda, S AF Agata, N Umanoff, H Milhollen, M Fram, R Kufe, D Kharbanda, S TI NM-3, a novel angiogenesis inhibitor, potentiates dexamethasone-induced apoptosis in multiple myeloma cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 ILEX Oncol Inc, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 325 BP 3719S EP 3719S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800321 ER PT J AU Keohan, M Skubitz, K Priebat, DA Paradise, C Infortuno, J Demitri, G AF Keohan, M Skubitz, K Priebat, DA Paradise, C Infortuno, J Demitri, G TI Phase II study of CT-2584 in patients with mesenchymal tumors (MT). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Columbia Univ, Coll Phys & Surg, New York, NY USA. Univ Minnesota, Minneapolis, MN 55455 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Cell Therapeut Inc, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 381 BP 3730S EP 3730S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800375 ER PT J AU Faircloth, GT Grant, W Hornicek, F AF Faircloth, GT Grant, W Hornicek, F TI In vivo combinations of chemotherapeutic agents with Ecteinascidin 743 (Et743) against solid tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. PharmaMar SA, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 387 BP 3731S EP 3732S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800381 ER PT J AU Hornicek, F Morioka, H Shao, L Faircloth, GT Weissbach, L AF Hornicek, F Morioka, H Shao, L Faircloth, GT Weissbach, L TI Effect of Ecteinascidin-743 and plasminogen related protein B on a human chondrosarcoma xenograft tumor in mice. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. PharmaMar USA, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 398 BP 3734S EP 3734S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800392 ER PT J AU Reid, JM Cha, S Buckner, JC Petros, WP Friedman, HS Tourt-Uhlig, S Walker, A Kuhn, JG Prados, M Supko, JG Gilbert, MR Batchelor, TT Schaaf, L Gaylor, SK McGovren, JP Gallo, JM AF Reid, JM Cha, S Buckner, JC Petros, WP Friedman, HS Tourt-Uhlig, S Walker, A Kuhn, JG Prados, M Supko, JG Gilbert, MR Batchelor, TT Schaaf, L Gaylor, SK McGovren, JP Gallo, JM TI Pharmacokinetics of CPT-11 in glioma patients: Pooled analysis of data from 4 NCI-sponsored trials (Duke university, NABTC, NABTT, NCCTG). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Mayo Clin, Rochester, NY USA. Duke Univ, Durham, NC 27706 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MD Anderson Canc Ctr, Houston, TX USA. Pharmacia Corp, Peapack, NJ USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RI Schaaf, Larry/A-9417-2008; Gilbert, Mark/J-7494-2016 OI Gilbert, Mark/0000-0003-2556-9722 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 415 BP 3737S EP 3737S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800409 ER PT J AU Joscheck, C Fiedler, W Algenstaedt, P Mende, T Wolfram, L Stoll, B Ruether, W Hansen-Algenstaedt, N AF Joscheck, C Fiedler, W Algenstaedt, P Mende, T Wolfram, L Stoll, B Ruether, W Hansen-Algenstaedt, N TI Acute myelocytic leukemia stimulates angiogenesis of both host and cancer associated endothelial cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Univ Hamburg Hosp, D-2000 Hamburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 466 BP 3747S EP 3748S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800459 ER PT J AU George, D Jonasch, E Hart, L Lentz, J Parker, K Henry, A Pfister, C Dugan, M Laurent, D Clark, J Kaelin, WG Oh, W Kantoff, P AF George, D Jonasch, E Hart, L Lentz, J Parker, K Henry, A Pfister, C Dugan, M Laurent, D Clark, J Kaelin, WG Oh, W Kantoff, P TI A phase I, dose-escalating and pharmacokinetic (PK) study of the VEGF-receptor inhibitor PTK787/ZK222584 (PTK/ZK) in patients with advanced renal cell or prostate carcinomas. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharmaceut, E Hanover, NJ USA. Schering AG, D-1000 Berlin, Germany. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 548 BP 3764S EP 3764S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800540 ER PT J AU Chandra, J Mow, B Weisberg, E Griffin, J Sausville, EA Tefferi, A Kaufmann, SH AF Chandra, J Mow, B Weisberg, E Griffin, J Sausville, EA Tefferi, A Kaufmann, SH TI Effects of the bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on leukemic cells in vitro. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 571 BP 3768S EP 3769S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800563 ER PT J AU Cao, W Cavacini, LA Posner, MR AF Cao, W Cavacini, LA Posner, MR TI CD40, a novel regulator of head and neck squamous cell carcinoma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 610 BP 3776S EP 3776S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800602 ER PT J AU Puchalski, TA Demetri, GD Garcia-Carbonero, R Ryan, DP Clark, JW Harmon, D Butkiewicz, L Maki, RG Lopez-Lazaro, L Jimeno, J Supko, JG AF Puchalski, TA Demetri, GD Garcia-Carbonero, R Ryan, DP Clark, JW Harmon, D Butkiewicz, L Maki, RG Lopez-Lazaro, L Jimeno, J Supko, JG TI The total body clearance of Ecteinascidin 743 is independent of body surface area and other variables related to body size. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Partners Canc Ctr, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Pharma Mar SA, Clin Res & Dev, Madrid, Spain. RI IBIS, NUEVAS TERAPIA/P-3415-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA 716 BP 3798S EP 3798S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800708 ER PT J AU Jain, RK AF Jain, RK TI In vivo imaging of gene expression, physiological function and therapeutic response in tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract ID SOLID TUMORS; MOLECULAR MEDICINE; DELIVERY; GROWTH; ANGIOGENESIS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA P810 BP 3816S EP 3817S PG 2 WC Oncology SC Oncology GA 491RE UT WOS:000172121800802 ER PT J AU Kaelin, WG AF Kaelin, WG TI Targeting the Rb pathway in human cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA P823 BP 3821S EP 3821S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800816 ER PT J AU Mahmood, U AF Mahmood, U TI Functional imaging approaches to molecular targets. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA W833 BP 3825S EP 3825S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800826 ER PT J AU Haber, DA Lee, SB Ellisen, LW Palmer, R Wong, J Reynolds, P Zhang, H AF Haber, DA Lee, SB Ellisen, LW Palmer, R Wong, J Reynolds, P Zhang, H TI The Wilms tumor gene WT1: Searching for function using expression profile analysis. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 2001 VL 7 IS 11 SU S MA W845 BP 3829S EP 3829S PG 1 WC Oncology SC Oncology GA 491RE UT WOS:000172121800839 ER PT J AU Zytkovicz, TH Fitzgerald, EF Marsden, D Larson, CA Shih, VE Johnson, DM Strauss, AW Comeau, AM Eaton, RB Grady, GF AF Zytkovicz, TH Fitzgerald, EF Marsden, D Larson, CA Shih, VE Johnson, DM Strauss, AW Comeau, AM Eaton, RB Grady, GF TI Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: A two-year summary from the New England newborn screening program SO CLINICAL CHEMISTRY LA English DT Article ID COA DEHYDROGENASE-DEFICIENCY; RAPID DIAGNOSIS; MCAD DEFICIENCY; INBORN-ERRORS; ACYLCARNITINE ANALYSIS; QUANTITATIVE-ANALYSIS; METABOLISM; MUTATION; GENE; PHENYLKETONURIA AB Background: Tandem mass spectrometry (MS/MS) is rapidly being adopted by newborn screening programs to screen dried blood spots for > 20 markers of disease in a single assay. Limited information is available for setting the marker cutoffs and for the resulting positive predictive values. Methods: We screened > 160 000 newborns by MS/MS. The markers were extracted from blood spots into a methanol solution with deuterium-labeled internal standards and then were derivatized before analysis by MS/MS. Multiple reaction monitoring of each sample for the markers of interest was accomplished in similar to1.9 min. Cutoffs for each marker were set at 6-13 SD above the population mean. Results: We identified 22 babies with amino acid disorders (7 phenylketonuria, 11 hyperphenylalaninemia, 1 maple syrup urine disease, I hypermethioninemia, 1 arginosuccinate lyase deficiency, and 1 argininemia) and 20 infants with fatty and organic acid disorders (10 medium-chain acyl-CoA dehydrogenase deficiencies, 5 presumptive short-chain acyl-CoA dehydrogenase deficiencies, 2 propionic acidemias, 1 camitine palmitoyltransferase 11 deficiency, 1 methylcrotonyl-CoA carboxylase deficiency, and 1 presumptive very-long chain acyl-CoA dehydrogenase deficiency). Approximately 0.3% of all newborns screened were flagged for either amino acid or acylcamitine markers; approximately one-half of all the flagged infants were from the 5% of newborns who required neonatal intensive care or had birth weights < 1500 g. Conclusions: In screening for 23 metabolic disorders by MS/MS, an mean positive predictive value of 8% can be achieved when using cutoffs for individual markers determined empirically on newborns. (C) 2001 American Association for Clinical Chemistry. C1 Univ Massachusetts, Sch Med, New England Newborn Screening Program, Jamaica Plain, MA 02130 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp East, Amino Acid Lab, Boston, MA 02129 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. RP Zytkovicz, TH (reprint author), Univ Massachusetts, Sch Med, New England Newborn Screening Program, 305 South St, Jamaica Plain, MA 02130 USA. NR 34 TC 298 Z9 324 U1 7 U2 43 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2001 VL 47 IS 11 BP 1945 EP 1955 PG 11 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 484UG UT WOS:000171707500003 PM 11673361 ER PT J AU Tanaka, Y Koido, S Chen, DS Gendler, SJ Kufe, D Gong, JL AF Tanaka, Y Koido, S Chen, DS Gendler, SJ Kufe, D Gong, JL TI Vaccination with allogeneic dendritic induces antitumor immunity in cells fused to carcinoma cells MUC1 transgenic mice SO CLINICAL IMMUNOLOGY LA English DT Article DE allogeneic and syngeneic DC fusions; fusion cell vaccines; anti-tumor immunity; reversal of tolerance to MUC1 ID CYTOTOXIC T-LYMPHOCYTES; IN-VITRO; ANTIGEN; GENERATION; RESPONSES; TOLERANCE; INDUCTION; PEPTIDE; GENE; VIVO AB Fusions of autologous tumor cells with allogeneic dendritic cells (DC) represent an approach for the induction of antitumor immunity. In the present studies, we investigated the antitumor effects of vaccinating MUC1-transgenic (MUC1.Tg) mice with MC38/MUC1 carcinoma cells fused to allogeneic DC from BALB/c mice (allo-DC, H-2(d)) or syngeneic DC from C57BL/6 mice (syn-DC, H-2(b)). Both allo and syn fusion cells (FC/MUC1) expressed MHC class II, costimulatory molecules, and the MUC1 antigen. Allo-FC/MUC1 exhibited dual expression of MHC class I haplotypes (H-2(d)/H-2(b)) and MUC1 antigen. By contrast, only H-2(b) and MUC1 antigen were expressed by syn-FC/MUC1. CTLs from MUC1.Tg mice immunized with allo- or syn-FC/MUC1 fusion cells lysed MC38/MUC1 targets. Moreover, immunization with allo- or syn-FC/MUC1 was effective in eliminating established MUC1-positive pulmonary metastases in MUC1.Tg mice. These results indicate that immunization of MUC1.Tg mice with syn- or allo-FC/MUC1 is effective in reversing immunologic unresponsiveness to MUC1 antigen and inducing immunity against MUC1-positive tumors. The findings in the present study have broader clinical implications for fusion cell vaccines. (C) 2001 Academic Press. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Mayo Clin, Scottsdale, AZ 85259 USA. RP Gong, JL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 87057-01] NR 40 TC 51 Z9 52 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD NOV PY 2001 VL 101 IS 2 BP 192 EP 200 DI 10.1006/clim.2001.5112 PG 9 WC Immunology SC Immunology GA 494AJ UT WOS:000172255600009 PM 11683578 ER PT J AU Miller, MC Berger, RA Petrella, AJ Karmas, A Rubash, HE AF Miller, MC Berger, RA Petrella, AJ Karmas, A Rubash, HE TI The Ranawat Award Paper - Optimizing femoral component rotation in total knee arthroplasty SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Knee-Society CY MAR, 2001 CL SAN FRANCISCO, CALIFORNIA SP Knee AB Femoral component rotation is important in total knee arthroplasty to optimize patellofemoral and tibiofemoral kinematics. More recently, the epicondylar axis has been cited as the definitive landmark for femoral component rotation. However, there are few studies to support the validity of this rotational landmark and its effect on the patellofemoral and tibiofemoral articulations. In the current study, a total knee arthroplasty was done in 11 knees from cadavers. The knees were tested with various femoral component rotations from 5 degrees internal rotation to 5 degrees external rotation referenced to the epicondylar axis and to the posterior femoral condyles. Each knee acted as its own internal control. The knees were actively ranged from 0 degrees to 100 degrees by a force on the quadriceps tendon in an Oxford knee simulator. Three-dimensional kinematics of all three components were measured whereas a multiaxial transducer imbedded in the patella measured patellofemoral forces. Femoral component rotation parallel to the epicondylar axis resulted in the most normal patellar tracking and minimized patellofemoral shear forces early in flexion. This optimal rotation also minimized tibiofemoral wear motions. These beneficial effects of femoral rotation were less reproducibly related to the posterior condyles. Rotating the femoral component either internal or external to the epicondylar axis worsened knee function by increasing tibiofemoral wear motion and significantly worsening patellar tracking with increased shear forces early in flexion. Based on the current study, the femoral component should be rotationally aligned parallel to the epicondylar axis to avoid patellofemoral and tibiofemoral complications. C1 Duquesne Univ, Pittsburgh, PA 15282 USA. Rush Presbyterian Hosp, Dept Orthopaed Surg, Chicago, IL USA. Univ Pittsburgh, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Miller, MC (reprint author), Duquesne Univ, 129 HSB, Pittsburgh, PA 15282 USA. NR 28 TC 136 Z9 149 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2001 IS 392 BP 38 EP 45 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 491BA UT WOS:000172087100005 PM 11716411 ER PT J AU Ekong, AS Foster, CS Roque, MR AF Ekong, AS Foster, CS Roque, MR TI Eye involvement in autoimmune blistering diseases SO CLINICS IN DERMATOLOGY LA English DT Article ID EPIDERMOLYSIS-BULLOSA-ACQUISITA; INTRAVENOUS IMMUNOGLOBULIN THERAPY; PEMPHIGOID AUTOANTIBODIES REACT; CONJUNCTIVAL INVOLVEMENT; IGG AUTOANTIBODIES; OCULAR INVOLVEMENT; BETA-4 INTEGRIN; CELL-ADHESION; EPILIGRIN; VULGARIS C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02115 USA. RP Foster, CS (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Immunol Serv, 243 Charles St, Boston, MA 02115 USA. NR 79 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0738-081X J9 CLIN DERMATOL JI Clin. Dermatol. PD NOV-DEC PY 2001 VL 19 IS 6 BP 742 EP 749 DI 10.1016/S0738-081X(00)00182-6 PG 8 WC Dermatology SC Dermatology GA 494GH UT WOS:000172273000012 PM 11705684 ER PT J AU Blais, MA Kelley, JM Holdwick, DJ Hilsenroth, MJ AF Blais, MA Kelley, JM Holdwick, DJ Hilsenroth, MJ TI The perceived clarity and understandability of the DSM-IV personality disorder criteria sets SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID AXIS-II; RELIABILITY AB One of the expressed aims of the DSM-IV revision process was to "increase the clarity" and the understandability of the personality disorder (PD) criteria. This was an important goal as previous research had showed the DSM-III-R PD criteria to have problems with clarity. To assess the degree to which this goal was achieved, we had two groups (psychiatrists and lay persons) rate the clarity of the DSM-IV PD criteria and the criteria for major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). The lay group rated five of the 10 PDs criteria sets and the criteria for PTSD as being significantly more clear than did the mental health professionals. No difference was seen between the two groups on their ratings of the MDD criteria. In addition, the professional group rated two of the PD criteria sets (borderline and schizotypal) as being less clear than the MDD criteria, while the lay group rated eight of the PD criteria sets as being more clear than the MDD criteria. Copyright (C) 2001 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Inpatient Psychiat Serv, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Arkansas, Dept Psychol, Fayetteville, AR 72701 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Inpatient Psychiat Serv, Dept Psychiat, Blake 11,32 Fruit St, Boston, MA 02114 USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 2001 VL 42 IS 6 BP 466 EP 470 DI 10.1053/comp.2001.27902 PG 5 WC Psychiatry SC Psychiatry GA 493GT UT WOS:000172214300005 PM 11704937 ER PT J AU Petersen, T Bottonari, K Alpert, JE Fava, M Nierenberg, AA AF Petersen, T Bottonari, K Alpert, JE Fava, M Nierenberg, AA TI Use of the five-factory inventory in characterizing patients with major depressive disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; 5-FACTOR MODEL; PERSONALITY DIMENSIONS; BIPOLAR; UNIPOLAR AB Research on personality traits has suggested an association between depression and certain personality traits, such as neuroticism and extraversion. Costa and McCrae's five-factor personality inventory (NEO) has been shown to measure personality traits in a nonclinical population, but its use has not been fully explored in clinical populations. This study aims to compare NEO results in a sample of depressed outpatients with published test norms, and determine if different levels of neuroticism and extraversion are associated with differences in certain psychosocial and clinical characteristics. Seventy-six depressed outpatients participating in antidepressant clinical trials completed this self-report questionnaire before beginning pharmacological treatment. Diagnosis of major depressive disorder (MDD) was made using the Structured Clinical Interview for DSM-III-R or DSM-IV and the severity of depression was measured with the 17-item Hamilton Depression Rating Scale (HAM-D). The three analyses conducted were as follows: (1) NEO factor scores were compared with published normative means; (2) three groups, based on level of neuroticism, were compared on certain psychosocial and clinical characteristics; and (3) three groups, based on level of extraversion, were compared on the same psychosocial and clinical characteristics. Both the males and females obtained T score values for the Neuroticism Scale 1.5 SD above the mean, for the Extraversion Scale 1.5 SD below the mean, and for the Conscientiousness Scale 1.5 SD below the mean. No significant differences were found between subjects with different levels of neuroticism and extraversion, although a trend did exist indicating a positive relationship between neuroticism and severity of depression. Depressed outpatients experience frequent negative affects, have irrational thought processes, cope with stress poorly, have difficulty controlling impulses, prefer to be alone, and have difficulty carrying out tasks. Future studies should examine how such personality factors affect response to treatment and course of illness. Copyright (C) 2001 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. RP Petersen, T (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 29 TC 34 Z9 34 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 2001 VL 42 IS 6 BP 488 EP 493 DI 10.1053/comp.2001.27897 PG 6 WC Psychiatry SC Psychiatry GA 493GT UT WOS:000172214300009 PM 11704941 ER PT J AU Bernard, GR Ely, EW Wright, TJ Fraiz, J Stasek, JE Russell, JA Mayers, I Rosenfeld, BA Morris, PE Yan, SB Helterbrand, JD AF Bernard, GR Ely, EW Wright, TJ Fraiz, J Stasek, JE Russell, JA Mayers, I Rosenfeld, BA Morris, PE Yan, SB Helterbrand, JD CA rhAPC Sepsis Study Grp TI Safety and dose relationship of recombinant human activated protein C for coagulopathy in severe sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE recombinant proteins; activated protein C; sepsis; septic shock; severe sepsis; D-dimer; phase II clinical trial; randomized controlled trial; disseminated intravascular coagulopathy; critical care; inflammation ID DISSEMINATED INTRAVASCULAR COAGULATION; CRITICALLY ILL PATIENTS; NECROSIS-FACTOR-ALPHA; PURPURA FULMINANS; SEPTIC SHOCK; MENINGOCOCCAL DISEASE; ANTITHROMBIN-III; PROGNOSTIC VALUE; ORGAN FAILURE; FACTOR-V AB Objectives: To assess the safety and effect on coagulopathy of a range of doses of recombinant human activated protein C (rhAPC). To determine an effective dose and duration of rhAPC for use in future clinical trials. Design: Double-blind, randomized, placebo-controlled, multicenter, dose-ranging (sequential), phase II clinical trial. Setting., Forty community or academic medical institutions in United States and Canada. Patients. One hundred thirty-one adult patients with severe sepsis. Interventions. Intravenous infusion of rhAPC (12, 18, 24, or 30 mug/kg/hr) or placebo for 48 or 96 hrs. Measurements and Main Results. No significant differences in incidence of serious bleeding events (4% rhAPC, 5% placebo, p > .999) or incidence of serious adverse events (39% rhAPC, 46% placebo, p = 0.422) between rhAPC- and placebo-treated patients were observed. One of 53 rhAPC-treated patients with suitable immunogenicity samples had a low level, transient, non-neutralizing anti-APC antibody response not associated with any clinical adverse event. Significant dose-dependent decreases in both D-dimer (p < 0.001) and end of infusion interleukin 6 levels (p = .021) were demonstrated. No statistically significant effects on fibrinogen or platelet counts were observed. A nonstatistically significant 15% relative risk reduction in 28-day all-cause mortality was observed between rhAPC- and placebo-treated patients. Conclusions. rhAPC was safe and well-tolerated and demonstrated a dose-dependent reduction in D-dimer and interleukin 6 levels relative to placebo. The dose of 24 mug/kg/hr for 96 hrs was selected for use in future clinical studies. C1 Vanderbilt Univ, Sch Med, Med Ctr,Dept Med, Med Ctr N,Div Allergy Pulm & Crit Care Med, Nashville, TN 37232 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. St Vincent Hosp, Res Dept, Indianapolis, IN USA. Baylor Coll Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Univ Alberta, Dept Med, Edmonton, AB, Canada. Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med & Surg, Baltimore, MD USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RP Bernard, GR (reprint author), Vanderbilt Univ, Sch Med, Med Ctr,Dept Med, Med Ctr N,Div Allergy Pulm & Crit Care Med, T-1208, Nashville, TN 37232 USA. RI Stasek, Jerome/E-4138-2011 NR 59 TC 186 Z9 201 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2001 VL 29 IS 11 BP 2051 EP 2059 DI 10.1097/00003246-200111000-00003 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 490WL UT WOS:000172076700003 PM 11700394 ER PT J AU Koseoglu, M Eroglu, A Toner, M Sadler, KC AF Koseoglu, M Eroglu, A Toner, M Sadler, KC TI Starfish Oocytes form intracellular ice at unusually high temperatures SO CRYOBIOLOGY LA English DT Article DE starfish oocytes; cryopreservation; freezing; intracellular ice formation ID EMBRYOS; CRYOPRESERVATION; PERMEABILITY AB Starfish oocytes, eggs, and embryos are popular models for studying meiotic maturation, fertilization, and embryonic development. Their large (170- to 200-mum) oocytes are obtainable in copious amounts and are amenable to manipulations that mammalian oocytes are not. The most formidable obstacle to working with marine oocytes is their seasonal availability, yet a successful means of preserving them for use during the nonreproductive season has not been reported, The aim of this study was to investigate the response of starfish oocytes to freezing with rapid and slow cooling rates under a variety of conditions to develop a cryopreservation protocol for these cells. Cryomicroscopic observation revealed that starfish oocytes in isotonic medium undergo intracellular ice formation (IIF) at very high subzero temperatures, such that the mean difference between the temperature of extracellular ice formation (T-EIF) and IIF (T-IIF) Was less than 3degreesC and the average T-IIF was approximately between -4 and -6degreesC. Neither partial cellular dehydration nor addition of the cryopreservative dimethyl sulfoxide significantly depressed the T-IIF. Under some conditions, we observed ice nucleation at multiple locations within the cytoplasm, suggesting that several factors contribute to the unusually high T-IIF during controlled-rate freezing and thus vitrification may be a more suitable method for cryoproserving these cells. (C) 2001 Elsevier Science (USA). C1 Bosphorus Univ, Dept Mol Biol & Genet, TR-80815 Bebek, Istanbul, Turkey. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Shriners Burns Inst,Ctr Engn Med, Boston, MA 02115 USA. RP Sadler, KC (reprint author), Bosphorus Univ, Dept Mol Biol & Genet, TR-80815 Bebek, Istanbul, Turkey. NR 22 TC 15 Z9 17 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0011-2240 J9 CRYOBIOLOGY JI Cryobiology PD NOV PY 2001 VL 43 IS 3 BP 248 EP 259 DI 10.1006/cryo.2001.2348 PG 12 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 533AQ UT WOS:000174507600006 PM 11888218 ER PT J AU Walker, WA AF Walker, WA TI Immunology SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA USA. RP Walker, WA (reprint author), 114 16th St 114-3502, Charlestown, MA 02129 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 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2001 VL 17 IS 6 BP 541 EP 544 DI 10.1097/00001574-200111000-00010 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 489CC UT WOS:000171973600010 ER PT J AU Sakaguchi, T Brand, S Reinecker, HC AF Sakaguchi, T Brand, S Reinecker, HC TI Mucosal barrier and immune mediators SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID TIGHT JUNCTION STRANDS; BRONCHISEPTICA DERMONECROTIZING TOXIN; INTEGRAL MEMBRANE-PROTEINS; NECROSIS-FACTOR-ALPHA; ACTIN STRESS FIBERS; EPITHELIAL-CELLS; INTERCELLULAR-JUNCTIONS; ENDOTHELIAL-CELLS; INTERFERON-GAMMA; DIRECT BINDING AB The intestinal mucosa functions is an immunologic organ that plays a major role in the development of oral tolerance and host-defense mechanisms. Antigens must cross the intestinal epithelium in a controlled manner to interact with dendritic anti gen-presenting cells, because bacteria or their products are a primary risk factor for the development of intestinal inflammation. Therefore, the regulation of the intestinal epithelial cell barrier is central to the development of intestinal immunity and inflammation, but the involved mechanisms are largely unknown. Intestinal barrier function relies on the formation of tight junctions at the apical contact areas of intestinal epithelial cells. Tight junctions have a highly dynamic structure whose permeability, assembly, or disassembly can be regulated by a variety of cellular and metabolic mediators, including cytokines, which have major functions in the immune system. Immune modulators control tight junction dependent intestinal barrier function during development, wound healing, and pathologic processes such as cancer, infection, and chronic inflammation. Curr Opin Gastroenterol 2001, 17:573-577 (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, 32 Fruit St, Boston, MA 02114 USA. NR 75 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2001 VL 17 IS 6 BP 573 EP 577 DI 10.1097/00001574-200111000-00016 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 489CC UT WOS:000171973600016 PM 17031221 ER PT J AU Tolkoff-Rubin, N AF Tolkoff-Rubin, N TI Dialysis: new views on old questions SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Editorial Material C1 Massachusetts Gen Hosp, GRB 130, Hemodialysis CAPD Renal Transplantat, Boston, MA 02114 USA. RP Tolkoff-Rubin, N (reprint author), Massachusetts Gen Hosp, GRB 130, Hemodialysis CAPD Renal Transplantat, 55 Fruit St, Boston, MA 02114 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 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD NOV PY 2001 VL 10 IS 6 BP 739 EP 740 DI 10.1097/00041552-200111000-00002 PG 2 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 490KZ UT WOS:000172052200002 ER PT J AU Boxem, M van den Heuvel, S AF Boxem, M van den Heuvel, S TI lin-35 Rb and cki-1 Cip/Kip cooperate in developmental regulation of G1 progression in C-elegans SO DEVELOPMENT LA English DT Article DE C. elegans; cyclin; CDK; pRb; Cip/Kip; cell cycle ID NEMATODE CAENORHABDITIS-ELEGANS; DEPENDENT KINASE INHIBITOR; CELL-CYCLE PROGRESSION; DROSOPHILA EMBRYOGENESIS; RETINOBLASTOMA GENE; CDK INHIBITORS; PRB PHOSPHORYLATION; TARGETED DISRUPTION; DEFICIENT CELLS; CHIMERIC MICE AB We have investigated the regulation of cell-cycle entry in C. elegans, taking advantage of its largely invariant and completely described pattern of somatic cell divisions. In a genetic screen, we identified mutations in cyd-1 cyclin D and cdk-4 Cdk4/6. Recent results indicated that during Drosophila development, cyclin D-dependent kinases regulate cell growth rather than cell division. However, our data indicate that C. elegans cyd-1 primarily controls G1 progression. To investigate whether cyd-1 and cdk-4 solely act to overcome GI inhibition by retinoblastoma family members, we constructed double mutants that completely eliminate the function of the retinoblastoma family and cyclin D-Cdk4/6 kinases. Inactivation of lin-35 Rb, the single Rb-related gene in C elegans, substantially reduced the DNA replication and cell-division defects in cyd-1 and cdk-4 mutant animals. These results demonstrate that lin-35 Rb is an important negative regulator of G1/S progression and probably a downstream target for cyd-1 and cdk-4. However, as the suppression by lin-35 Rb is not complete, cyd-1 and cdk-4 probably have additional targets. An additional level of control over G1 progression is provided by Cip/Kip kinase inhibitors. We demonstrate that lin-35 Rb and cki-1 Cip/Kip contribute nonoverlapping levels of G1/S inhibition in C. elegans. Surprisingly, loss of cki-1, but not lin-35, results in precocious entry into S phase. We suggest that a rate limiting role for cki-1 Cip/Kip rather than lin-35 Rb explains the lack or cell-cycle phenotype of lin-35 mutant animals. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th Floor, Charlestown, MA 02129 USA. EM heuvel@helix.mgh.harvard.edu RI Boxem, Mike/B-8857-2011; van den Heuvel, Sander/B-8892-2011 OI Boxem, Mike/0000-0003-3966-4173; NR 60 TC 91 Z9 99 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD NOV PY 2001 VL 128 IS 21 BP 4349 EP 4359 PG 11 WC Developmental Biology SC Developmental Biology GA 496HF UT WOS:000172389600021 PM 11684669 ER PT J AU Perlingeiro, RCR Kyba, M Daley, GQ AF Perlingeiro, RCR Kyba, M Daley, GQ TI Clonal analysis of differentiating embryonic stem cells reveals a hematopoietic progenitor with primitive erythroid and adult lymphoid-myeloid potential SO DEVELOPMENT LA English DT Article DE embryonic stem cells; hematopoiesis; adult reconstitution; BCR/ABL ID YOLK-SAC; IN-VITRO; DEFINITIVE HEMATOPOIESIS; COMMON PRECURSOR; MOUSE EMBRYO; ES CELLS; GENE; INVITRO; CULTURE; MICE AB Embryonic stem (ES) cells differentiate into multiple hematopoietic lineages during embryoid body formation in vitro, but to date, an ES-derived hematopoietic stem cell has not been identified and subjected to clonal analysis in a manner comparable with hematopoietic stem cells from adult bone marrow. As the chronic myeloid leukemia-associated BCR/ABL oncogene endows the adult hematopoietic stem cell with clonal dominance without inhibiting pluripotent lymphoid and myeloid differentiation, we have used BCR/ABL as a tool to enable engraftment and clonal analysis. We show that embryoid body-derived hematopoietic progenitors expressing BCR/ABL maintain a primitive hematopoietic blast stage of differentiation and generate only primitive erythroid cell types in vitro. These cells can be cloned, and when injected into irradiated adult mice, they differentiate into multiple myeloid cell types as well as T and B lymphocytes. While the injected cells express embryonic (beta -H1) globin, donor-derived erythroid cells in the recipient express only adult (beta -major) globin, suggesting that these cells undergo globin gene switching and developmental maturation in vivo. These data demonstrate that an embryonic hematopoietic stem cell arises in vitro during ES cell differentiation that constitutes a common progenitor for embryonic erythroid and definitive lymphoid-myeloid hematopoiesis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Whitehead Inst, Cambridge, MA 02142 USA. RP Daley, GQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. OI Kyba, Michael/0000-0002-5579-7534 FU NCI NIH HHS [CA86991, CA76418]; NIDDK NIH HHS [DK59279] NR 37 TC 69 Z9 73 U1 0 U2 1 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 NOV PY 2001 VL 128 IS 22 BP 4597 EP 4604 PG 8 WC Developmental Biology SC Developmental Biology GA 499FC UT WOS:000172559500019 PM 11714684 ER PT J AU Ferguson, CA Tucker, AS Heikinheimo, K Nomura, M Oh, P Li, E Sharpe, PT AF Ferguson, CA Tucker, AS Heikinheimo, K Nomura, M Oh, P Li, E Sharpe, PT TI The role of effectors of the activin signalling pathway, activin receptors IIA and IIB, and Smad2, in patterning of tooth development SO DEVELOPMENT LA English DT Article DE activin; activin receptors; Smad2; Irx1; tooth development; mouse ID MESSENGER RIBONUCLEIC-ACIDS; IROQUOIS HOMEOBOX GENES; RAT EMBRYOGENESIS; MURINE DENTITION; XENOPUS HOMOLOG; NEURAL PLATE; EXPRESSION; MOUSE; IDENTIFICATION; FOLLISTATINS AB The gene for activin betaA is expressed in the early odontogenic mesenchyme of all murine teeth but mutant mice show a patterning defect where incisors and mandibular molars fail to develop but maxillary molars develop normally. In order to understand why maxillary molar tooth development can proceed in the absence of activin, we have explored the role of mediators of activin signalling in tooth development. Analysis of tooth development in activin receptor II and Smad2 mutants shows that a similar tooth phenotype to activin betaA mutants can be observed. In addition, we identify a novel downstream target of activin signalling, the Iroquois-related homeobox gene, Irx1, and show that its expression in activin betaA mutant embryos is lost in all tooth germs, including the maxillary molars. These results strongly suggest that other transforming growth factor beta molecules are not stimulating the activin signalling pathway in the absence of activin. This was confirmed by a non-genetic approach using exogenous soluble receptors to inhibit all activin signalling in tooth development, which reproduced the genetic phenotypes. Activin, thus, has an essential role in early development of incisor and mandibular molar teeth but this pathway is not required for development of maxillary molars. C1 Guys Hosp, Univ London Kings Coll, GKT Dent Inst, Dept Craniofacial Dev, London SE1 9RT, England. Univ Turku, Inst Dent, Dept Oral & Maxillofacial Surg, FIN-20520 Turku, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Sharpe, PT (reprint author), Guys Hosp, Univ London Kings Coll, GKT Dent Inst, Dept Craniofacial Dev, Floor 28,London Bridge, London SE1 9RT, England. RI Tucker, Abigail/K-1788-2016 OI Tucker, Abigail/0000-0001-8871-6094 NR 41 TC 48 Z9 50 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 NOV PY 2001 VL 128 IS 22 BP 4605 EP 4613 PG 9 WC Developmental Biology SC Developmental Biology GA 499FC UT WOS:000172559500020 PM 11714685 ER PT J AU Wang, F Hull, RL Vidal, J Cnop, M Kahn, SE AF Wang, F Hull, RL Vidal, J Cnop, M Kahn, SE TI Islet amyloid develops diffusely throughout the pancreas before becoming severe and replacing endocrine cells SO DIABETES LA English DT Article ID DIABETES-MELLITUS; BETA-CELL; TRANSGENIC MICE; MOUSE MODEL; MACACA-NIGRA; POLYPEPTIDE; INSULIN; LANGERHANS; SECRETION; HYPERGLYCEMIA AB Islet amyloid occurs in > 90% of type 2 diabetic patients and may play a role in the pathogenesis of this disease. To determine whether islet amyloid occurs diffusely throughout the pancreas, whether it affects islets equally, and whether it decreases islet endocrine cells, we characterized islet amyloidosis by computerized fluorescence microscopy in transgenic mice that develop typical islet amyloid. These mice produce the unique amyloidogenic component of human islet amyloid, human islet amyloid polypeptide (hIAPP). The prevalence of amyloid (number of islets containing amyloid/total number of islets x 100) and the severity of amyloid (Sigma amyloid area/Sigma islet area x 100) were found to be uniform throughout the pancreas. Furthermore, a high prevalence of amyloid was observed in islets when the severity of amyloid was only 1.5% of the islet area, suggesting a diffuse distribution of amyloid from the very early stages of islet amyloidosis. In 12 hIAPP transgenic mice with an amyloid severity of 9.6 +/- 3.4%, the proportion of islets composed of beta- and delta -cells was reduced in the transgenic mice compared with 6 nontransgenic mice that do not develop amyloid (beta -cells: 62.9 +/- 3.1% vs. 75.5 +/- 0.9%, P = 0.02; delta -cells: 2.8 +/- 0.5% vs. 4.4 +/- 0.4%, P = 0.05), whereas the proportion of islets composed of alpha -cells did not significantly differ between the two groups of mice. In the individual islets in these transgenic mice, amyloid severity was inversely correlated with P-cell, (r = -0.59, P < 0.0001), alpha -cell (r = -0.32, P < 0.0001), and delta -cell (r = -0.25, P < 0.0001) areas. In conclusion, islet amyloidosis occurs uniformly throughout the pancreas, affecting all islets before becoming severe. A reduction in islet endocrine mass starts at this early stage of islet amyloid development and progresses as amyloid mass increases. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, 151,1660 S Columbian Way, Seattle, WA 98108 USA. OI Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU NIDDK NIH HHS [DK-17047, DK-50703] NR 27 TC 45 Z9 46 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 NOV PY 2001 VL 50 IS 11 BP 2514 EP 2520 DI 10.2337/diabetes.50.11.2514 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488CJ UT WOS:000171917200014 PM 11679429 ER PT J AU Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Gingerich, R Egan, JM Finegood, DT Elahi, D AF Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Gingerich, R Egan, JM Finegood, DT Elahi, D TI Effect of glucagon-like peptide 1 on non-insulin-mediated glucose uptake in the elderly patient with diabetes SO DIABETES CARE LA English DT Article ID IN-VITRO; IV; POLYPEPTIDE; DEGRADATION; DISPOSAL; HORMONE; DISPOSITION; TOLERANCE; RATES; NIDDM AB An important cause of elevated glucose levels in elderly patients with diabetes is an alteration in non-insulin-mediated glucose uptake (NIMGU). Glucagon-like peptide 1 (GLP-1) is an intestinal insulinotropic hormone. It has been proposed that this hormone also lowers glucose levels by enhancing NIMGU. This study was conducted to determine whether GLP-1 augments ;NIMGU in elderly patients with diabetes, a group in which NIMGU is known to be impaired. Studies were conducted on 10 elderly patients with type 2 diabetes (aged 75 +/- 2 years, BMI 27 +/- 1 kg/m(2)) who under-went paired 240-min glucose clamp studies. In each study, octreotide was infused to suppress endogenous insulin release, and tritiated glucose methodology was used to measure glucose production and disposal rates. For the first 180 min, no glucose was infused. From 180 to 240 min, glucose was increased to 11 mmol/l using the glucose clamp protocol. In the GLP-1 study, GLP-1 was infused from 30 to 240 min. In a subsequent control Study, insulin was infused using the glucose clamp protocol from 30 to 240 min to match the insulin levels that occurred during the GLP-1 infusion study, During hyperglycemia, GLP-1 enhanced glucose disposal (control study: 2.52 +/- 0.19 mg . kg(-1). min(-1) GLP-1 study: 2.90 +/- 0.17 mg . kg(-1). min(-1); P < 0.0001). Hepatic glucose output,vas not different between studies. We conclude that GLP-1 may partially reverse the defect in NIMGU that occurs in elderly patients with diabetes. C1 Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Physiol, Vancouver, BC V5Z 1M9, Canada. Simon Fraser Univ, Sch Kinesiol, Burnaby, BC V5A 1S6, Canada. NIA, Gerontol Res Ctr, Lab Clin Physiol, NIH, Baltimore, MD 21224 USA. Linco Res, St Charles, MO USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Lab Mol Endocrinol, Howard Hughes Med Inst, Boston, MA USA. RP Meneilly, GS (reprint author), Vancouver Hosp & Hlth Sci Ctr, UBC Site,2211 Wesbrook Mall,Rm S 169, Vancouver, BC V6T 2B5, Canada. NR 36 TC 45 Z9 46 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2001 VL 24 IS 11 BP 1951 EP 1956 DI 10.2337/diacare.24.11.1951 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 488LZ UT WOS:000171937800018 PM 11679463 ER PT J AU Olaleye, D Perkins, BA Bril, V AF Olaleye, D Perkins, BA Bril, V TI Evaluation of three screening tests and a risk assessment model for diagnosing peripheral neuropathy in the diabetes clinic SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article DE screening for neuropathy; diagnostic test; diabetes mellitus; risk assessment model ID LOWER-EXTREMITY AMPUTATION; NERVE-CONDUCTION; CRITERIA; PREVENTION AB Objective: with the aim of evaluating predictive power, three simple screening tests as alternates to nerve conduction tests for diagnosing diabetic peripheral neuropathy (DPN) were investigated. Results of the screening tests, along with the subjects' demographic and clinical characteristics, were planned as the variables for the development of a risk assessment tool for predicting DPN. Design: this is a cross-sectional multi-group comparison study. The study utilized a predictive model derived from one subset of the study population, and prospectively tested in the other subset to predict the presence of neuropathy. Setting: Diabetic Neuropathy Research Clinic of the Toronto General Hospital and University Health Network in Toronto, Ontario, Canada from June 1998 to August 1999. Sample population: data come from 478 subjects consisting of non-diabetic reference subjects, and patients with type I and type 2 diabetes mellitus. Outcome measures: nerve conduction studies (NCS) comprised the primary defined outcome. The three screening sensory tests examined in the study were the Semmes-Weinstein 10 g monofilament examination (SWME), superficial pain sensation, and vibration by the on-off method. Results: the three screening tests are significantly and positively correlated with NCS. An increase in the number of insensate responses in the screening test is associated with an increase in the abnormal NCS score. The strength of the association between NCS and each sensory test was greater when the neuropathy severity stage of the subject was added to the model. Both the SWME and vibration by the on-off method tests demonstrated sufficient statistical power to differentiate non-diabetic control subjects from subjects with diabetes, as well as to differentiate subjects with diabetes with and without neuropathy. These two tests, when compared with NCS, also demonstrated acceptable diagnostic performance characteristics in terms of high sensitivity and specificity, total number of correctly predicted cases, and receiver-operating characteristic curves. Conclusion: this data, through the development of a model involving training and validation sets, demonstrates that the knowledge of clinical risk factors alters the interpretation of sensory tests for DPN. This finding lends further support to the validity of simple sensory testing maneuvers in the conditional diagnosis of DPN. We recommend annual screening with either the SWME or vibration by the on-off method in the primary care and diabetes clinics. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 iBiomatics LLC, Cary, NC 27513 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Univ Toronto, Toronto Gen Hosp, Hlth Network, Div Neurol, Toronto, ON M5G 1L7, Canada. RP Olaleye, D (reprint author), iBiomatics LLC, 11000 Weston Pkwy,Suite 100, Cary, NC 27513 USA. NR 24 TC 53 Z9 58 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD NOV PY 2001 VL 54 IS 2 BP 115 EP 128 DI 10.1016/S0168-8227(01)00278-9 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 493HK UT WOS:000172216400006 PM 11640995 ER PT J AU Schlozman, SC AF Schlozman, SC TI The shrink in the classroom - Coping with the unthinkable SO EDUCATIONAL LEADERSHIP LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD NOV PY 2001 VL 59 IS 3 BP 86 EP 88 PG 3 WC Education & Educational Research SC Education & Educational Research GA 499DJ UT WOS:000172555500020 ER PT J AU Morra, M Lu, J Poy, F Martin, M Sayos, J Calpe, S Gullo, C Howie, D Rietdijk, S Thompson, A Coyle, AJ Denny, C Yaffe, MB Engel, P Eck, MJ Terhorst, C AF Morra, M Lu, J Poy, F Martin, M Sayos, J Calpe, S Gullo, C Howie, D Rietdijk, S Thompson, A Coyle, AJ Denny, C Yaffe, MB Engel, P Eck, MJ Terhorst, C TI Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells SO EMBO JOURNAL LA English DT Article DE antigen-presenting cells; crystal structure; EAT-2; SAP; XLP ID LINKED LYMPHOPROLIFERATIVE-DISEASE; EPSTEIN-BARR-VIRUS; AFFINITY PHOSPHOTYROSYL PEPTIDE; HUMAN B-LYMPHOCYTES; NATURAL-KILLER; PROTEIN EXPRESSION; CRYSTAL-STRUCTURES; ENCODING GENE; CUTTING EDGE; ACTIVATION AB The T and natural killer (NK) cell-specific gene SAP (SH2D1A) encodes a 'free SH2 domain' that binds a specific tyrosine motif in the cytoplasmic tail of SLAM (CD150) and related cell surface proteins. Mutations in SH2D1A cause the X-linked lymphoproliferative disease, a primary immunodeficiency. Here we report that a second gene encoding a free SH2 domain, EAT-2, is expressed in macrophages and B lympho cytes. The EAT-2 structure in complex with a phosphotyrosine peptide containing a sequence motif with Tyr281 of the cytoplasmic tail of CD150 is very similar to the structure of SH2D1A complexed with the same peptide. This explains the high affinity of EAT-2 for the pTyr motif in the cytoplasmic tail of CD150 but, unlike SH2D1A, EAT-2 does not bind to non-phosphorylated CD150. EAT-2 binds to the phosphorylated receptors CD84, CD150, CD229 and CD244, and acts as a natural inhibitor, which interferes with the recruitment of the tyrosine phosphatase SHP-2. We conclude that EAT-2 plays a role in controlling signal transduction through at least four receptors expressed on the surface of professional antigen-presenting cells. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Millennium Pharmaceut Inc, Inflammat Div, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Univ Barcelona, Fac Med, Dept Cellular Biol & Pathol, E-08007 Barcelona, Spain. RP Morra, M (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. RI Sayos, Joan/B-6119-2009; OI Sayos, Joan/0000-0002-4664-3461; Martin, Margarita/0000-0002-9245-4899 FU NIAID NIH HHS [P01 AI035714, P01-AI-35714] NR 51 TC 91 Z9 97 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 1 PY 2001 VL 20 IS 21 BP 5840 EP 5852 DI 10.1093/emboj/20.21.5840 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 491HY UT WOS:000172104000004 PM 11689425 ER PT J AU Brown, DFM AF Brown, DFM TI Treatment options for deep venous thrombosis SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article ID MOLECULAR-WEIGHT HEPARINS; INTRAVENOUS UNFRACTIONATED HEPARIN; VEIN-THROMBOSIS; INITIAL TREATMENT; PULMONARY-EMBOLISM; UPPER-EXTREMITY; ANTICOAGULANT-THERAPY; THROMBOLYTIC THERAPY; OUTPATIENT MANAGEMENT; SUBCUTANEOUS HEPARIN AB Once the diagnosis of deep venous; thrombosis (DVT) has been established the focus shifts to management of the disease, The goals of acute treatment of DVT are several: arrest growth of the thrombus, dissolve or remove the thrombus, and prevent embolizations of the thrombus. Although these goals have remained constant, the initial management of DVT has undergone a series of evolutions during the past decade, affecting both acute treatment and disposition decisions. As this article discusses, emergency medicine is at the cutting edge of these changes. C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02114 USA. NR 67 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8627 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD NOV PY 2001 VL 19 IS 4 BP 913 EP + DI 10.1016/S0733-8627(05)70226-1 PG 12 WC Emergency Medicine SC Emergency Medicine GA 498TA UT WOS:000172525500007 PM 11762279 ER PT J AU Hassani, S Braunstein, GD Seibel, MJ Brickman, AS Geola, F Pekary, AE Hershman, JM AF Hassani, S Braunstein, GD Seibel, MJ Brickman, AS Geola, F Pekary, AE Hershman, JM TI Alendronate therapy of primary hyperparathyroidism SO ENDOCRINOLOGIST LA English DT Article ID BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; PARATHYROID SURGERY; CALCIUM; DIPHOSPHONATE; OSTEOPOROSIS; REPLACEMENT AB There is a growing interest in preventing bone loss through medical treatment of patients with primary hyperparathyroidism who have mild asymptomatic disease or who are not candidates for surgical parathyroidectomy. Bisphosphonates are inhibitors of bone resorption and could be useful to improve the bone resorption of hyperparathyroidism. There fore, we conducted a controlled trial of alendronate therapy in patients with primary hyperparathyroidism. Participants were 45 asymptomatic patients with primary hyperparathyroidism who either had mild disease or a coexistent disease making surgical therapy hazardous or who refused parathyroidectomy. Their femoral bone mineral density (BMD) was in the osteoporotic or osteopenic range. Eight assigned to alendronate therapy had complete biochemical studies performed prospectively before therapy, then after 1 month, and every 2 months for 1 year. Another 37 patients were assigned as: 11 to the alendronate group and 26 to the nonalendronate or control group; all of them had regular follow-up with their endocrinologists. All the patients administered the alendronate therapy were administered 10 mg/d of alendronate for 1 year. Bone mineral density was measured by dual-energy x-ray absorptiometry at the lumbar spine and proximal femur initially and at 12 months in all patients. Eight patients had measurement of BMD of the radius and a complete biochemical profile. By 12 months, patients using alendronate had a significant increase in BMD at the lumbar spine by 3.38% and at the femoral neck by 3.05%. In contrast, the control group had losses of 1.41% at the lumbar spine and 0.80% at the femoral neck. The markers of bone turnover (urine pyridinoline and deoxypyridinoline) decreased in the eight patients using alendronate at 1 to 4 months. The serum total alkaline phosphatase level decreased significantly at 6 months and remained decreased at 12 months. Serum calcium, phosphorus, intact parathyroid hormone, 1,25-dihydroxyvitamin D-3. and 25-hydroxyvitamin D levels did not change significantly, but there was a small increase in ionized calcium at 6 months. We conclude that in patients with hyperparathyroidism, alendronate prevents bone loss and significantly improves BMD at the lumbar spine and femoral neck. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Kaiser Permanente Med Ctr, Woodland Hills, CA USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. Concord Hosp, Dept Endocrinol & Metab, Sydney, NSW, Australia. W Los Angeles VA Med Ctr, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Hershman, JM (reprint author), VA Greater Los Angeles Healthcare Syst, Endocrinol-111D,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 28 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD NOV-DEC PY 2001 VL 11 IS 6 BP 459 EP 464 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 501EC UT WOS:000172669000005 ER PT J AU Llevadot, J Giugliano, RP Antman, EM Wilcox, RG Gurfinkel, EP Henry, T McCabe, CH Charlesworth, A Thompson, S Nicolau, JC Tebbe, U Sadowski, Z Braunwald, E AF Llevadot, J Giugliano, RP Antman, EM Wilcox, RG Gurfinkel, EP Henry, T McCabe, CH Charlesworth, A Thompson, S Nicolau, JC Tebbe, U Sadowski, Z Braunwald, E CA InTIME II Investigators TI Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction SO EUROPEAN HEART JOURNAL LA English DT Article DE myocardial infarction; fibrinolysis; availability of on-site catheterization; outcomes ID CORONARY-ANGIOGRAPHY; UNITED-STATES; CARDIAC PROCEDURES; CARDIOGENIC-SHOCK; EARLY REVASCULARIZATION; SUCCESSFUL THROMBOLYSIS; II-TRIAL; HOSPITALS; FACILITIES; MANAGEMENT AB Aims To compare management and clinical outcomes in hospitals stratified by the availability or on-site catheterization in InTIME-II, a multicentre trial comparing alteplase with lanoteplase for acute myocardial infarction. Methods and Results We studied 15 078 patients enrolled in 35 countries and 855 hospitals. Thirty-one percent of hospitals had 24-h. 25% day-only, and 44% no on-site catheterization facilities. Rates of cardiac angiography (57%, 38%, 26%) and revascularization (37%, 21%, 17%) were higher in hospitals with increasing access to on-site facilities (P <0.0001). The presence of a 24-h on-site facility was the strongest predictor of angiography during the index admission (odds ratio 4.17, 95% CI 3.85-4.54). There were no major differences in patient outcomes at 30 days when hospitals were stratified by availability of on-site catheterization. Adjusted 1-year mortality was similar between groups of hospitals (odds ratio for day-only 0.94 [0.80-1.09] and odds ratio for no availability 0.95 [0.83-1.10] compared to hospitals with 24-h facilities). Conclusions There is a marked variation in procedure use by the availability of on-site catheterization with no major differences in patient outcomes. There is a need for additional randomized trials in the Current era to address both the appropriate selection of patients and timing of invasive procedures in ST-elevation acute myocardial infarction. (C) 2001 The European Society of Cardiology. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Queens Med Ctr, Div Cardiovasc Med, Nottingham NG7 2UH, England. Fdn Favaloro, Buenos Aires, DF, Argentina. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Nottingham Clin Res Grp, Nottingham, England. Inst Coracao, Sao Paulo, Brazil. Klinikum Lippe Detmold, Detmold, Germany. Klin Choroby Wiencowej, Warsaw, Poland. RP Giugliano, RP (reprint author), TIMI Study Off, 333 Longwood Ave,Suite 402, Boston, MA 02115 USA. RI Nicolau, Jose/E-1487-2012 NR 41 TC 19 Z9 19 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD NOV PY 2001 VL 22 IS 22 BP 2104 EP 2115 DI 10.1053/euhj.2001.2622 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 492XA UT WOS:000172191800012 PM 11686667 ER PT J AU Suzue, K Reinherz, EL Koyasu, S AF Suzue, K Reinherz, EL Koyasu, S TI Critical role of NK but not NKT cells in acute rejection of parental bone marrow cells in F1 hybrid mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE hybrid resistance; gamma(c) knockout mouse; Rag-2 knockout mouse ID NATURAL-KILLER-CELLS; RECEPTOR-GAMMA CHAIN; T-CELL; GRAFT-REJECTION; RESISTANCE; MOLECULES; CLONING; LY-49; SPECIFICITY; RECOGNITION AB F1 hybrid mice vigorously reject transplanted parental bone marrow (BM) cells, which is a phenomenon called "hybrid resistance (HR)". Since NK1.1(+) cells play crucial role in HR, both NK1.1(+)CD3(+) NKT cells and NK1.1(+)CD3(-) NK cells have been possible candidates of effector cells. To elucidate the major effector cells in HR, we employed Rag-2(-/-) mice devoid of T, B, and NKT cells and cytokine receptor common gamma subunit and Rag-2 double-deficient (gamma (-/-(y))(c)-Rag-2(-/-)) mice lacking all lymphoid cells including NK cells. Rag-2(-/-) F1 hybrid mice rejected parental BM cells to the extent similar to wild-type (WT) F1 hybrids. In contrast, male gammaC(-/y)-Rag-2(-/-) F1 hybrid mice were unable to reject parental BM cells. After reconstitution with NK but not NKT cells, male gamma (-/y)(c)-Rag-2(-/-) F1 hybrid mice restored the ability to reject parental BM cells. Collectively, it is concluded that NKT cells play little role, if any, and NK cells are the only cells involved in HR. C1 Keio Univ, Sch Med, Dept Immunol & Microbiol, Shinjuku Ku, Tokyo 1608582, Japan. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Koyasu, S (reprint author), Keio Univ, Sch Med, Dept Immunol & Microbiol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. RI Koyasu, Shigeo/J-5583-2015 OI Koyasu, Shigeo/0000-0001-9585-3038 FU NIAID NIH HHS [R01 AI19807] NR 26 TC 21 Z9 21 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2001 VL 31 IS 11 BP 3147 EP 3152 DI 10.1002/1521-4141(200111)31:11<3147::AID-IMMU3147>3.0.CO;2-F PG 6 WC Immunology SC Immunology GA 494JD UT WOS:000172278000003 PM 11745331 ER PT J AU Kaur, A Alexander, L Staprans, SI Denekamp, L Hale, CL McClure, HM Feinberg, MB Desrosiers, RC Johnson, RP AF Kaur, A Alexander, L Staprans, SI Denekamp, L Hale, CL McClure, HM Feinberg, MB Desrosiers, RC Johnson, RP TI Emergence of cytotoxic T lymphocyte escape mutations in nonpathogenic simian immunodeficiency virus infection SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE simian immunodeficiency virus; sooty mangabey; CTL escape ID SOOTY MANGABEYS; IN-VIVO; SELECTION; VARIANTS; IMMUNODOMINANT; REPLICATION; PROGRESSION; RESPONSES; PRESSURE; DYNAMICS AB Although CTL escape has been well documented in pathogenic simian immunodeficiency virus (SIV) infection, there is no information on CTL escape in nonpathogenic SIV infection in nonhuman primate hosts like the sooty mangabeys. CTL responses and sequence variation in the SIV nef gene were evaluated in one sooty mangabey and one rhesus macaque inoculated together with the same stock of cloned SIVmac239. Each animal developed an immunodominant response to a distinct CTL epitope in Nef, aa 157-167 in the macaque and aa. 20-28 in the mangabey. Nonsynonymous mutations in their respective epitopes were observed in both animals and resulted in loss of CTL recognition. These mutations were present in the majority of proviral DNA sequences at 16 weeks post infection in the macaque and >2 years post infection in the mangabey. These results document the occurrence of CTL escape in a host that does not develop AIDS, and adds to the growing body of evidence that CTL exert significant selective pressure in SIV infection. C1 Harvard Univ, Div Immunol, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Harvard Univ, Dept Microbiol, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Emory Univ, Yerkes Reg Primate Res Ctr, Div Res Resources, Atlanta, GA 30322 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Emory Univ, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. RP Kaur, A (reprint author), Harvard Univ, Div Immunol, Sch Med, New England Reg Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR00168, RR00165]; NIAID NIH HHS [AI44763, AI38559, AI25328]; NIDA NIH HHS [DA12121] NR 22 TC 46 Z9 46 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2001 VL 31 IS 11 BP 3207 EP 3217 DI 10.1002/1521-4141(200111)31:11<3207::AID-IMMU3207>3.0.CO;2-H PG 11 WC Immunology SC Immunology GA 494JD UT WOS:000172278000009 PM 11745337 ER PT J AU Scardino, A Alves, P Gross, DA Tourdot, S Graff-Dubois, S Angevin, E Firat, H Chouaib, S Lemonier, F Nadler, LM Cardoso, AA Kosmatopoulos, K AF Scardino, A Alves, P Gross, DA Tourdot, S Graff-Dubois, S Angevin, E Firat, H Chouaib, S Lemonier, F Nadler, LM Cardoso, AA Kosmatopoulos, K TI Identification of HER-2/neu immunogenic epitopes presented by renal cell carcinoma and other human epithelial tumors SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE immunotherapy; tumor antigen; HER-2/neu; CTL; renal cell carcinoma ID CYTOTOXIC T-LYMPHOCYTES; OVARIAN-CANCER; INFILTRATING LYMPHOCYTES; METASTATIC MELANOMA; BREAST-CANCER; NEU ONCOGENE; CTL EPITOPES; ANTIGEN; PEPTIDE; IMMUNOTHERAPY AB HER-2/neu is a tumor-associated antigen overexpressed in a large variety of human tumors. Eight HER-2/neu peptides displaying HLA-A*0201 anchoring motifs were selected and tested for their binding affinity to HLA-A*0201 and their capacity to elicit cytotoxic T lymphocyte (CTL) responses in both HLA-A*0201 transgenic mice and in HLA-A*0201(+) healthy donors. Two high-affinity (p5 and p48) and one intermediate-affinity (p1023) peptides triggered CTL responses in both transgenic mice and humans, comparable to those observed for the well-known HER2/neu dominant peptide p369. CTL induced in transgenic mice lysed HLA-A*0201(+) RMA cells infected with recombinant HER-2/neu but not cells infected with wild-type vaccinia virus. Human CTL lysed HLA-A*0201 HER-2/neu tumor cells of different origins (breast, colon, lung and renal cancer) irrespective of the expression levels of HER-2/neu. Importantly, primed CTL specific for these epitopes were detected in freshly isolated tumor-infiltrating lymphocytes from three renal cell carcinoma patients. Therefore, the HER2/neu peptides p5, p48 and p1023 may be good candidates for immunotherapy of a broad spectrum of tumors, including renal cell carcinoma. C1 Inst Gustave Roussy, INSERM 487, F-94805 Villejuif, France. Inst Gustave Roussy, Clin Immunol Lab, Villejuif, France. CNRS, URA 1923, Genethon 3, Evry, France. Inst Pasteur, Dept Sida Retrovirus, Unite Immun Cellulaire Antivirale, Paris, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Kosmatopoulos, K (reprint author), Inst Gustave Roussy, INSERM 487, 39 Rue Camille Desmoulins, F-94805 Villejuif, France. RI Chouaib, Salem/F-7939-2016; OI ANGEVIN, Eric/0000-0001-6249-7209 FU NCI NIH HHS [P01-CA68484] NR 35 TC 29 Z9 30 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2001 VL 31 IS 11 BP 3261 EP 3270 DI 10.1002/1521-4141(200111)31:11<3261::AID-IMMU3261>3.0.CO;2-4 PG 10 WC Immunology SC Immunology GA 494JD UT WOS:000172278000015 PM 11745343 ER PT J AU Petersen, A Hansson, O Puschban, Z Sapp, E Romero, N Castilho, RF Sulzer, D Rice, M DiFiglia, M Przedborski, S Brundin, P AF Petersen, A Hansson, O Puschban, Z Sapp, E Romero, N Castilho, RF Sulzer, D Rice, M DiFiglia, M Przedborski, S Brundin, P TI Mice transgenic for exon 1 of the Huntington's disease gene display reduced striatal sensitivity to neurotoxicity induced by dopamine and 6-hydroxydopamine SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE cell death; Huntington's disease; oxidative stress; striatum ID MOUSE MODEL; INTRASTRIATAL INJECTION; NEUROLOGICAL PHENOTYPE; OXIDATIVE STRESS; CELL-DEATH; MUTATION; EXPRESSION; GLUTAMATE; TOXICITY; NEURONS AB Huntington's disease is an autosomal dominant hereditary neurodegenerative disorder characterized by severe striatal cell loss. Dopamine (DA) has been suggested to play a role in the pathogenesis of the disease. We have previously reported that transgenic mice expressing exon 1 of the human Huntington gene (R6 lines) are resistant to quinolinic acid-induced striatal toxicity. In this study we show that with increasing age, R6/1 and R6/2 mice develop partial resistance to DA- and 6-hydroxydopamine-mediated toxicity in the striatum. Using electron microscopy, we found that the resistance is localized to the cell bodies and not to the neuropil. The reduction of dopamine and cAMP regulated phosphoprotein of a molecular weight of 32 kDa (DARPP-32) in R6/2 mice does not provide the resistance, as DA-Induced striatal lesions are not reduced in size in DARPP-32 knockout mice. Neither DA receptor antagonists nor a N-methyl-D-aspartate (NMDA) receptor blocker reduce the size of DA-induced striatal lesions, suggesting that DA toxicity is not dependent upon DA- or NMDA receptor-mediated pathways. Moreover, superoxide dismutase-1 overexpression, monoamine oxidase inhibition and the treatment with the free radical scavenging spin-trap agent phenyl-butyl-tert-nitrone (PBN) also did not block DA toxicity. Levels of the antioxidant molecules, glutathione and ascorbate were not increased in R6/1 mice, Because damage to striatal neurons following intrastriatal injection of 6-hydroxydopamine was also reduced in R6 mice, a yet-to-be identified antioxidant mechanism may provide neuroprotection in these animals. We conclude that striatal neurons of R6 mice develop resistance to DA-induced toxicity with age. C1 Lund Univ, Wallenberg Neurosci Ctr, Sect Neuronal Servival, S-22100 Lund, Sweden. Columbia Univ, Dept Neurol, New York, NY 10027 USA. Columbia Univ, Dept Pathol, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NYU, Sch Med, Dept Neurosurg, New York, NY USA. NYU, Sch Med, Dept Physiol & Neurosci, New York, NY USA. RP Petersen, A (reprint author), Lund Univ, Wallenberg Neurosci Ctr, Sect Neuronal Servival, S-22100 Lund, Sweden. RI Petersen, Asa/E-6064-2011; Castilho, Roger/G-3906-2012; Hansson, Oskar/A-7134-2013 OI Hansson, Oskar/0000-0001-8467-7286 FU NINDS NIH HHS [P50 NS38370, R01 NS38586, R29 NS37345] NR 55 TC 29 Z9 29 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2001 VL 14 IS 9 BP 1425 EP 1435 DI 10.1046/j.0953-816x.2001.01765.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 496XJ UT WOS:000172423400002 PM 11722604 ER PT J AU Hazzard, WR AF Hazzard, WR TI Clinical investigation: But why? SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Hazzard, WR (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,S-GEC-182, Seattle, WA 98108 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 0037-9727 J9 EXP BIOL MED JI Exp. Biol. Med. PD NOV PY 2001 VL 226 IS 10 BP 871 EP 872 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 487RU UT WOS:000171889700001 PM 11682692 ER PT J AU Allport, JR Weissleder, R AF Allport, JR Weissleder, R TI In vivo imaging of gene and cell therapies SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE MICROSCOPY; RAY COMPUTED-TOMOGRAPHY; DIFFUSE OPTICAL TOMOGRAPHY; IRON-OXIDE PARTICLES; TRAFFICKING IN-VIVO; LIVING ANIMALS; TRANSGENE EXPRESSION; TUMOR ANGIOGENESIS; NERVOUS-SYSTEM AB Molecular imaging can be broadly defined as the in vivo characterization and measurement of biological processes at the cellular and molecular level. In contrast to commonly used clinical imaging, it sets forth to probe the molecular abnormalities that are the basis of disease, rather than imaging the end effects of these molecular alterations. Development of new imaging technologies requires a multidisciplinary collaboration between biologists, chemists, physicists, and imaging scientists to create novel agents, signal amplification strategies, and imaging techniques that successfully address these questions. In this article we attempt to present some of the recent developments and show how molecular imaging can be used, at least experimentally, to assess specific molecular targets for gene- and cell-based therapies. In particular, we place emphasis on the development and use of experimental small-animal models, which are particularly inclined toward this approach, primarily in combination with magnetic resonance (MR), radionuclide, and optical imaging. In the future, specific imaging of disease targets will allow earlier detection and characterization of disease, as well as earlier and direct molecular assessment of treatment efficacy. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Harvard Univ, CMIR, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Charlestown, MA 02129 USA. RP Allport, JR (reprint author), Harvard Univ, CMIR, Sch Med, Massachusetts Gen Hosp,Dept Radiol, 149 13th St,Room 5416, Charlestown, MA 02129 USA. NR 100 TC 75 Z9 84 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD NOV PY 2001 VL 29 IS 11 BP 1237 EP 1246 DI 10.1016/S0301-472X(01)00739-1 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 490QA UT WOS:000172061500001 PM 11698119 ER PT J AU Bracy, JL Chase, CM Russell, PS Mauiyyedi, S Colvin, RB Iacomini, J AF Bracy, JL Chase, CM Russell, PS Mauiyyedi, S Colvin, RB Iacomini, J TI Induction of molecular chimerism by gene therapy prevents antibody-mediated heart transplant rejection SO GENE THERAPY LA English DT Article DE tolerance; antibodies; xenotransplantation; gene therapy ID NATURAL ANTIBODIES; MIXED CHIMERISM; MICE; TOLERANCE; CELLS; MOUSE; XENOTRANSPLANTATION; ALLOGRAFTS; MODEL AB In order for xenotransplantation to become a clinical reality, and fulfill its promise of overcoming shortages of human organs and tissues, rejection mediated by the host's immune system must first be overcome. In primates, preformed natural antibodies that bind the carbohydrate antigen Gal alpha1-3Gal beta1-4GlcNAc-R (alpha Gal), which is synthesized by UDP galactose:beta -D-galactosyl-1,4-N-acetyl-D-glucosaminide alpha (1-3)galactosyltransferase (E.C. 2.4.1.151) or simply alpha GT, mediate rigorous rejection of transplanted pig organs and tissues. In alpha GT knockout mice (GT(0) mice), which like humans contain in their serum antibodies that bind aGal, expression of a retrovirally transduced alpha GT in bone marrow-derived cells is sufficient to prevent production of alpha Gal-reactive antibodies. Here, we demonstrate that reconstitution of lethally irradiated GT(0) mice with alpha GT-transduced bone marrow cells from GT(0) littermates prevents antibody-mediated rejection of cardiac transplants from wild-type mice. These data suggest that gene therapy can be used to induce immunological tolerance to defined antigens and thereby overcome transplant rejection. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Surg, Transplant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149 13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [T32 AI 07529, AI43619, AI44268] NR 29 TC 13 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD NOV PY 2001 VL 8 IS 22 BP 1738 EP 1744 DI 10.1038/sj.gt.3301581 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 501DB UT WOS:000172666700009 PM 11892842 ER PT J AU Hinton, D Chau, H Nguyen, L Nguyen, M Pham, T Quinn, S Tran, M AF Hinton, D Chau, H Nguyen, L Nguyen, M Pham, T Quinn, S Tran, M TI Panic disorder among Vietnamese refugees attending a psychiatric clinic: Prevalence and subtypes SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Vietnamese refugees; panic disorder; panic disorder subtypes; trauma; catastrophic cognitions ID POSTTRAUMATIC-STRESS-DISORDER; SOUTHEAST-ASIAN REFUGEES; ANXIETY SENSITIVITY; PRIMARY-CARE; HEART-RATE; WAR; VETERANS; SYMPTOMS; TORTURE; SUFFOCATION AB This study surveys Vietnamese refugees attending two psychiatric clinics to determine both the prevalence of panic disorder (PD) as well as panic attack subtypes in those suffering PD. A culturally valid adaptation of the SCID-panic module (the Vietnamese Panic Disorder Survey or VPDS) was administered to 100 Vietnamese refugees attending two psychiatric clinics. Utilizing culturally sensitive panic probes, the VPDS provides information regarding both the presence of PD and panic attack subtypes during the month prior to interview. Of 100 patients surveyed, 50 (50%) currently suffered PD. Among the 50, patients suffering PD, the most common panic attack subtypes during the previous month were the following: "orthostatic dizziness" (74% of the 50 panic disorder patients [PDPs]), headache (50% of PDPs), wind-induced/temperature-shift-induced (24% of PDPs), effort-induced (18% of PDPs), gastro-intestinal (16% of PDPs), micturition-induced (8% of PDPs), out-of-the-blue palpitations (24% of PDPs), and out-of-the-blue shortness of breath (16% of PDPs). Five mechanisms are adduced to account for this high PD prevalence as well as the specific profile of subtypes: 1) a trauma-caused panic attack diathesis; 2) trauma-event cues; 3) ethnic differences in physiology; 4) catastrophic cognitions generated by cultural syndromes; and 5) a modification of Clark's spiral of panic. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. N Suffolk Mental Hlth Ctr, SE Asian Clin, E Boston, MA USA. Arbour Counseling, Lowell, MA USA. RP Hinton, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. FU NIMH NIH HHS [K23 MH066253, K23 MH066253-05, R01 MH094312] NR 65 TC 31 Z9 31 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0163-8343 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2001 VL 23 IS 6 BP 337 EP 344 DI 10.1016/S0163-8343(01)00163-3 PG 8 WC Psychiatry SC Psychiatry GA 498UW UT WOS:000172529700006 PM 11738465 ER PT J AU Schipani, E Ryan, HE Didrickson, S Kobayashi, T Knight, M Johnson, RS AF Schipani, E Ryan, HE Didrickson, S Kobayashi, T Knight, M Johnson, RS TI Hypoxia in cartilage: HIF-1 alpha is essential for chondrocyte growth arrest and survival SO GENES & DEVELOPMENT LA English DT Article DE hypoxia; cartilage ID INDUCIBLE FACTOR 1-ALPHA; GENE-EXPRESSION; TUMOR-GROWTH; PHOSPHOGLYCERATE KINASE-1; O-2 HOMEOSTASIS; TARGET GENES; ANGIOGENESIS; DIFFERENTIATION; APOPTOSIS; BONE AB Breakdown or absence of vascular oxygen delivery is a hallmark of many common human diseases, including cancer, myocardial infarction, and stroke. The chief mediator of hypoxic response in mammalian tissues is the transcription factor hypoxia-inducible factor 1 (HIF-1), and its oxygen-sensitive component HIF-1 alpha. A key question surrounding HIF-1 alpha and the hypoxic response is the role of this transcription factor in cells removed from a functional vascular bed, in this regard there is evidence indicating that it can act as either a survival factor or induce growth arrest and apoptosis. To study more closely how HIF-1 alpha functions in hypoxia in vivo, we used tissue-specific targeting to delete HIF-1 alpha in an avascular tissue: the cartilaginous growth plate of developing bone. We show here the first evidence that the developmental growth plate in mammals is hypoxic, and that this hypoxia occurs in its interior rather than at its periphery. As a result of this developmental hypoxia, cells that lack HIF-1 alpha in the interior of the growth plate die. This is coupled to decreased expression of the CDK inhibitor p57, and increased levels of BrdU incorporation in HIF-1a null growth plates, indicating defects in HIF-1 alpha -regulated growth arrest occurs in these animals. Furthermore, we find that VEGF expression in the growth plate is regulated through both HIF-1 alpha -dependent and -independent mechanisms. In particular, we provide evidence that VEGF expression is up-regulated in a HIF-1 alpha -independent manner in chondrocytes surrounding areas of cell death, and this in turn induces ectopic angiogenesis. Altogether, our findings have important implications for the role of hypoxic response and HIF-1 alpha in development, and in cell survival in tissues challenged by interruption of vascular flow; they also illustrate the complexities of HIF-1 alpha response in vivo, and they provide new insights into mechanisms of growth plate development. C1 Univ Calif San Diego, Div Biol, Mol Biol Sect, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Johnson, RS (reprint author), Univ Calif San Diego, Div Biol, Mol Biol Sect, La Jolla, CA 92093 USA. FU NCI NIH HHS [CA82515, R01 CA082515]; NIAMS NIH HHS [AR44855, P50 AR044855] NR 38 TC 441 Z9 466 U1 4 U2 38 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 2001 VL 15 IS 21 BP 2865 EP 2876 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 489WT UT WOS:000172016000009 PM 11691837 ER PT J AU Hamlet, MRJ Perkins, LA AF Hamlet, MRJ Perkins, LA TI Analysis of corkscrew signaling in the drosophila epidermal growth factor receptor pathway during myogenesis SO GENETICS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; DORSAL-VENTRAL AXIS; EGF-RECEPTOR; TRANSCRIPTION FACTORS; EMBRYONIC MESODERM; DOCKING PROTEIN; EYE DEVELOPMENT; CELL FATES; MAP KINASE; TORSO RTK AB The Drosophila nonreceptor protein tyrosine phosphatase, Corkscrew (Csw), functions positively in multiple receptor tyrosine kinase (RTK) pathways, including signaling by the epidermal growth factor receptor (EGFR). Detailed phenotypic analyses of csw mutations have revealed that Csw activity is required in many of the same developmental processes that require EGFR function. However, it is still unclear where in the signaling hierarchy Csw functions relative to other proteins whose activities are also required downstream of the receptor. To address this issue, genetic interaction experiments were performed to place csw gene activity relative to the EGFR spitz (spi), rhomboid (rho), daughter of sevenless (DOS). kinase-suppressor of ras (ksr), ras1, D-raf, pointed (pnt), and moleskin. We followed the EGFR-dependent formation of VA2 muscle precursor cells as a sensitive assay for these genetic interaction studies. First, we established that Csw has a positive function during mesoderm development. Second, we found that tissue-specific expression of a gain-of-function csw, construct rescues loss-of-function mutations in other positive signaling genes upstream of rolled (rl)/MAPK in the EGFR pathway. Third, we were able to infer levels of EGFR signaling in various mutant backgrounds during myogenesis. This work extends previous Studies of Csw during Torso and Sevenless RTK signaling to include an in-depth analysis of the role of Csw in the EGFR signaling pathway. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Charlestown, MA 02129 USA. RP Perkins, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Rm 2425,114 16th St, Charlestown, MA 02129 USA. NR 55 TC 21 Z9 21 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD NOV PY 2001 VL 159 IS 3 BP 1073 EP 1087 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 501CR UT WOS:000172665800015 ER PT J AU Quiroz-Mercado, H Sanchez-Buenfil, E Guerrero-Naranjo, JL Ochoa-Contreras, D Ruiz-Cruz, M Marcellino, G D'Amico, DJ AF Quiroz-Mercado, H Sanchez-Buenfil, E Guerrero-Naranjo, JL Ochoa-Contreras, D Ruiz-Cruz, M Marcellino, G D'Amico, DJ TI Successful erbium: YAG laser-induced chorioretinal venous anastomosis for the management of ischemic central retinal vein occlusion - A report of two cases SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 23rd Meeting of the Club Jules Gonin CY SEP 06, 2000 CL TAORMINA, ITALY ID CYSTOID MACULAR EDEMA; MEMBRANE AB Background: Central retinal vein occlusion (CRVO) is a disorder with potentially blinding complications, particularly when associated with retinal ischemia. There is no reliable treatment for ischemic CRVO. Methods: We developed a new approach for ischemic cases of CRVO consisting of vitrectomy, posterior hyaloid detachment, and four erbium:YAG laser-induced chorioretinal anastomoses, one in each quadrant. Results: We report two cases of ischemic CRVO treated with this approach, with initial visual acuity of count fingers at 30 cm and hand movements respectively. After the surgery, there was resolution of hemorrhages and macular edema and visual improvement to 20/400 in the first case and to 20/180 in the second case. In both cases, there was successful creation of chorioretinal anastomoses. and there was no anterior segment neovascularization or other complications related to the surgery. Conclusion: This treatment shows promise in the management of the ischemic cases of CRVO, and further evaluation is justified. C1 Hosp Dr Luis Sanchez Bulnes, Retina Serv, APEC, Mexico City 04200, DF, Mexico. Coherent Med, Palo Alto, CA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Dept, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Quiroz-Mercado, H (reprint author), Hosp Dr Luis Sanchez Bulnes, Retina Serv, APEC, Vicente Garcia Torres 46, Mexico City 04200, DF, Mexico. NR 13 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD NOV PY 2001 VL 239 IS 11 BP 872 EP 875 DI 10.1007/s004170100338 PG 4 WC Ophthalmology SC Ophthalmology GA 503KF UT WOS:000172797100010 PM 11789869 ER PT J AU Meyer, JH Lembo, A Elashoff, JD Fass, R Mayer, EA AF Meyer, JH Lembo, A Elashoff, JD Fass, R Mayer, EA TI Duodenal fat intensifies the perception of heartburn SO GUT LA English DT Article DE gastro-oesophageal reflux disease; heartburn; perception; fat ID LOWER ESOPHAGEAL SPHINCTER; NUTRIENT-DRIVEN SATIETY; GASTROESOPHAGEAL-REFLUX; ACID EXPOSURE; SMALL-INTESTINE; MEALS; MECHANOSENSITIVITY; MODULATION; HUMANS AB Background-Patients with gastrooesophageal reflux disease (GORD) frequently report that meals high in fat worsen heartburn. Nevertheless, studies to determine whether high fat meals promote gastro-oesophageal reflux have produced conflicting and equivocal conclusions. Patients and methods-To determine, alternatively, whether fat in the small intestinal lumen intensifies the perception of heartburn, we studied 11 patients with typical heartburn from GORD. After being placed on omeprazole to suppress endogenous acid, these fasting subjects underwent oesophageal perfusions with graded doses of HCl at pH values of 1.0, 1.5, 2.0, and 2.5. Oesophageal perfusions were conducted while the duodenum was perfused with saline (control) and again with fat at 8 g/h. Results-Time to onset, intensity, and severity of heartburn varied with dose of oesophageal acid (p < 0.01). Time to onset was significantly (p < 0.01) shorter, and intensity and severity of heartburn significantly (p < 0.05) greater, during duodenal perfusion with fat. Conclusion-We conclude that duodenal fat intensifies the perception of heartburn. C1 Univ Calif Los Angeles, Sch Med,Dept Med,Div Gastroenterol, W Los Angeles Healthcare Syst, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, CURE, Neuroenter Dis Program, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Biostat Core Res Inst, Los Angeles, CA USA. RP Mayer, EA (reprint author), W Los Angeles Vet Affairs Med Ctr, Rm 223,Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM emayer@ucla.edu NR 27 TC 30 Z9 34 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD NOV PY 2001 VL 49 IS 5 BP 624 EP 628 DI 10.1136/gut.49.5.624 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 483PX UT WOS:000171645500009 PM 11600463 ER PT J AU Mutter, GL Baak, JPA Fitzgerald, JT Gray, R Neuberg, D Kust, GA Gentleman, R Gullans, SR Wei, LJ Wilcox, M AF Mutter, GL Baak, JPA Fitzgerald, JT Gray, R Neuberg, D Kust, GA Gentleman, R Gullans, SR Wei, LJ Wilcox, M TI Global expression changes of constitutive and hormonally regulated genes during endometrial neoplastic transformation SO GYNECOLOGIC ONCOLOGY LA English DT Article DE endometrial carcinoma; gene expression; steroid hormones; bioinformatics; microarray ID MICROSATELLITE INSTABILITY; ATYPICAL HYPERPLASIA; PROSTATE-CANCER; PTEN EXPRESSION; CELL-LINES; CARCINOMA; MUTATIONS; PROTEIN; MICROARRAYS; PROGESTIN AB Objective. Endometrioid endometrial carcinoma is caused by a combination of mutational events and hormonal factors. We used large-scale messenger RNA expression analysis to discover genes that distinguish neoplastic transformation and examine the patterns of tumor expression of those genes which are normally regulated during the menstrual cycle. Methods. Expression of approximately 6000 unique genes was quantified in 4 normal (2 proliferative, 2 secretory) and 10 malignant endometria using Affymetrix Hu6800 GeneChip probe arrays. Expression differences between normal and malignant tissue groups were measured by a test of statistical significance comparing the individual t statistic for each gene to the distribution of maximum t statistics among all genes following 1001 permutations of the tissue group assignments (Permax test). Hormonally responsive genes, selected by comparison of proliferative and secretory subsets of normal endometria using a combination of filters applied to the group means and t test rankings, were then examined in the tumors. Results. Fifty genes with a Permax <0.50 provided excellent discrimination between normal and malignant groups and were predominantly characterized by diminished expression levels in the cancers. We found that 100 genes which are hormonally regulated in normal tissues are expressed in a disordered and heterogeneous fashion in cancers, with tumors resembling proliferative more than secretory endometrium. Conclusion. Neoplastic transformation is accompanied by predominant loss of activity of many genes constitutively expressed in normal source tissues and absence of expression profiles which characterize the antitumorigenic progestin response. (C) 2001 Academic Press. C1 Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Med Centrum Alkmaar, Dept Pathol, Alkmaar, Netherlands. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Mutter, GL (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. RI Mutter, George/C-5819-2009 NR 33 TC 97 Z9 98 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 NOV PY 2001 VL 83 IS 2 BP 177 EP 185 DI 10.1006/gyno.2001.6352 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 490JW UT WOS:000172049600002 PM 11606070 ER PT J AU Duska, LR Garrett, A Rueda, BR Haas, J Chang, YC Fuller, AF AF Duska, LR Garrett, A Rueda, BR Haas, J Chang, YC Fuller, AF TI Endometrial cancer in women 40 years old or younger SO GYNECOLOGIC ONCOLOGY LA English DT Article ID PREMENOPAUSAL WOMEN; HER-2 NEU; CARCINOMA; AGE; OVEREXPRESSION; ADENOCARCINOMA; EXPRESSION; PROGESTIN; SURVIVAL; P53 AB Objective. The aim of this study was to characterize endometrial cancer in women 40 years of age and younger, with special attention toward body-mass index (BMI). Methods. A retrospective review of women age 40 and under with endometrial cancer was performed. Patients were identified via tumor registry data as well as a search of pathology department diagnoses over the dates 1980-1998. Data were abstracted regarding tumor grade and histology, stage, treatment, smoking, use of oral contraceptives, BMI, medical and family history, parity, and survival. Data were also collected with regard to uterine conservation and pregnancies following endometrial cancer diagnoses. Results. Ninety-five patients were identified. The age range was 24-40 years (median 37) with BMI ranging from 17.5 to 63.6 (median 28.4). Forty-eight patients (52%) were not obese, with BMI < 30. Seventy-six patients (80%) had stage I disease and 60 patients (63%) had grade 1 disease. All but 4 patients had endometrioid histology. Women with BMI < 25 were more likely to have advanced disease (P = 0.04) and more likely to have highrisk histology (P = 0.02). Of the 4 patients with high-risk histology (clear cell or serous papillary), all had BMI < 25. Twelve patients were treated medically rather than surgically, and 4 patients achieved pregnancy, with 5 live births. Conclusion. Women under 40 who are not obese are at higher risk of both advanced disease and high-risk histology. Further study at the molecular and genetic level is ongoing in our laboratory to determine whether the mechanism of disease is different in slender woman. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vincent Gynecol Serv, Div Gynecol Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Cox 120,100 Blossom St, Boston, MA 02114 USA. NR 24 TC 86 Z9 94 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 NOV PY 2001 VL 83 IS 2 BP 388 EP 393 DI 10.1006/gyno.2001.6434 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 490JW UT WOS:000172049600034 PM 11606102 ER PT J AU Seiden, MV Spitzer, TR McAfee, S Fuller, AF AF Seiden, MV Spitzer, TR McAfee, S Fuller, AF TI Successful pregnancy after high-dose cyclophosphamide, carboplatinum, and taxol with peripheral blood stem cell transplant in a young woman with ovarian carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian carcinoma; high-dose therapy; pregnancy ID BONE-MARROW TRANSPLANTATION; CHEMOTHERAPY; CANCER AB Background. Both ovarian carcinoma and high-dose chemotherapy tend to preclude future pregnancies. Case. We report a case of a young woman with borderline ovarian carcinoma and invasive tumor implants who underwent surgical debulking with preservation of future fertility followed by carboplatinum, paclitaxel (Taxol), and subsequent high-dose chemotherapy with subsequent peripheral blood stem cell rescue as part of a phase I clinical trial. After a brief period of amenorrhea, the patient had a successful pregnancy that was complicated by a spontaneous abortion in the first trimester. Several months later she conceived and delivered a healthy baby at term. Conclusions. To our knowledge this is the first reported case of pregnancy, after high-dose chemotherapy with stem cell transplant in a woman with ovarian carcinoma. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), 100 Blossom St,Cox 640, Boston, MA 02114 USA. NR 10 TC 6 Z9 7 U1 1 U2 1 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 NOV PY 2001 VL 83 IS 2 BP 412 EP 414 DI 10.1006/gyno.2001.6373 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 490JW UT WOS:000172049600039 PM 11606107 ER PT J AU Severus, WE Littman, AB Stoll, AL AF Severus, WE Littman, AB Stoll, AL TI Omega-3 fatty acids, homocysteine, and the increased risk of cardiovascular mortality in major depressive disorder SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID PLACEBO-CONTROLLED TRIAL; CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; AMERICAN-HEART-ASSOCIATION; ORAL S-ADENOSYLMETHIONINE; HEALTH-CARE PROFESSIONALS; SUDDEN CARDIAC DEATH; ALPHA-LINOLENIC ACID; BLOOD-CELL MEMBRANES; PLASMA HOMOCYSTEINE AB Depression Is associated with elevated rates of cardiovascular morbidity and mortality. This elevation seems to be due to a significantly increased risk of coronary artery disease and myocardial infarction and, once the ischemic heart disease is established, sudden cardiac death. Recent data suggest that the increased rates of cardiovascular disease in patients with depression may be the result of one or more still-unrecognized underlying physiological factors that predispose a patient to both depression and cardiovascular disease. Two possibly related factors that may have a causal relation with both depressive disorders and cardiovascular disease are an omega-3 fatty acid deficiency and elevated homocysteine levels. We present the available data connecting cardiovascular disease, depression, omega-3 fatty acids, and homocysteine. In addition, we suggest research strategies and some preliminary treatment recommendations that may reduce the increased risk of cardiovascular mortality in patients with major depressive disorder. C1 Univ Hosp Benjamin Franklin, Dept Psychiat, D-14050 Berlin, Germany. McLean Hosp, Psychopharmacol Res Lab, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Behav Med Div Prevent Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Severus, WE (reprint author), Univ Hosp Benjamin Franklin, Dept Psychiat, Eschenallee 3, D-14050 Berlin, Germany. FU NCCIH NIH HHS [IR01 AT00161-01] NR 101 TC 76 Z9 78 U1 4 U2 9 PU MOSBY, 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 NOV-DEC PY 2001 VL 9 IS 6 BP 280 EP 293 DI 10.1093/hrp/9.6.280 PG 14 WC Psychiatry SC Psychiatry GA 486RW UT WOS:000171831600002 PM 11600487 ER PT J AU Cutrer, FM AF Cutrer, FM TI Antiepileptic drugs: How they work in headache SO HEADACHE LA English DT Article DE GABA; gabapentin; glutamate; migraine; topiramate; valproate ID MIGRAINE PROPHYLAXIS; CALCIUM-CHANNEL; GABAPENTIN; VALPROATE; TOPIRAMATE; MECHANISMS; EPILEPSY; ANTICONVULSANT; SUBUNIT; MODEL AB Antiepileptic drugs (AEDs) are promising agents for the prevention of migraine and: other head pain. Migraine and epilepsy share several clinical features and respond to many of the same pharmacologic agents, suggesting that similar mechanisms may be involved in their pathophysiology. The mechanisms of action of AEDs are not fully understood, and a single drug may have more than one mechanism, both in epilepsy and in, migraine. Valproate, topiramate, and gabapentin are likely to affect nociception by modulating gamma-aminobutyric acid(GABA-) and/or glutamate-mediated neurotransmission. All three AEDs enhance GABA-mediated inhibition. Valproate and gabapentin interfere with GABA metabolism to prevent its ultimate conversion to succinate, and topiramate potentiates GABA-mediated inhibition by facilitating the action of GABA receptors. In addition, topiramate acts directly on non-N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate glutamate receptors. Valproate, topiramate, and possibly, gabapentin inhibit sodium ion channels. All three drugs modulate calcium ion channel activity.,Valproate blocks T-type calcium ion channels; topiramate inhibits high-voltage-activated L-type calcium ion channels; and gabapentin binds to the alpha (2)delta subunit of L-type calcium ion channels. AEDs may be useful in migraine prevention through such mechanisms as modulating the biochemical phenomena of aura or acting directly on the nociceptive system. Further evaluations of AEDs in migraine models will provide a better understanding of the pathophysiology and prevention of migraine. C1 Massachusetts Gen Hosp, Headache Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Cutrer, FM (reprint author), Massachusetts Gen Hosp, Headache Ctr, VBK-G05, Boston, MA 02114 USA. NR 24 TC 39 Z9 43 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0017-8748 J9 HEADACHE JI Headache PD NOV-DEC PY 2001 VL 41 SU 1 BP S3 EP S10 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 506KA UT WOS:000172968400001 PM 11903534 ER PT J AU Vernig, PG Schumacher, TA AF Vernig, PG Schumacher, TA TI Nuclear medicine survey recommendations for a changing regulatory environment SO HEALTH PHYSICS LA English DT Article DE operational topic; radiopharmaceuticals; surveys; regulations AB The revision of 10 CFR 35 approved on 23 September 2000 and due for implementation in 2001, reduces the number of required radiation and contamination surveys to one ambient radiation survey each day when art administration requiring a written directive is used. This paper compares the current requirements in 10 CFR 35; the single, remaining, specific requirement in the revised part 35; the Nuclear Regulatory Commission's guidance in the proposed NUREG SR1556 and the general requirement for surveys to demonstrate compliance with 10 CFR 20. We also make recommendations on what periodic surveys are prudent. C1 Denver VA Med Ctr, Denver, CO USA. RP Vernig, PG (reprint author), 1055 Clermont St, Denver, CO 80220 USA. EM peter.vernig@med.va.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD NOV PY 2001 VL 81 IS 5 SU S BP S70 EP S74 DI 10.1097/00004032-200111001-00012 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 485PD UT WOS:000171762000013 PM 11669196 ER PT J AU Sperling, RA Bates, JF Cocchiarella, AJ Schacter, DL Rosen, BR Albert, MS AF Sperling, RA Bates, JF Cocchiarella, AJ Schacter, DL Rosen, BR Albert, MS TI Encoding novel face-name associations: A functional MRI study SO HUMAN BRAIN MAPPING LA English DT Article DE memory; hippocampus; magnetic resonance imaging; prefrontal cortex; human ID MEDIAL TEMPORAL-LOBE; POSITRON EMISSION TOMOGRAPHY; WORKING-MEMORY; HIPPOCAMPAL-FORMATION; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; EPISODIC MEMORY; BRAIN ACTIVITY; SYSTEM; FMRI AB The process of forming new associations between previously unrelated items of information, such as a name and a face, likely requires the integration of activity within multiple brain regions. The hippocampus and related structures in the medial temporal lobe are thought to be particularly critical in binding together items of information. We studied eight healthy young subjects with functional magnetic resonance imaging (fMRI) during the encoding of novel face-name associations compared to viewing repeated face-name pairs. A consistent pattern of activation was observed in the hippocampus, pulvinar nucleus of the thalamus, fusiform and dorsolateral prefrontal. cortices across individual subjects. The location of the activation within the hippocampus was more anterior than previously reported in studies using similar novel vs. repeated paradigms with stimuli that did not specifically require relational processing among unrelated items. These data suggest that the process of forming new face-name associations is supported by a distributed network of brain regions, and provide additional evidence for the essential role of the hippocampus in associative memory processes. (C) 2001 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Memory Disorders Unit, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Sperling, RA (reprint author), Brigham & Womens Hosp, Memory Disorders Unit, Dept Neurol, 221 Longwood Ave, Boston, MA 02115 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [P01-AG04953]; NINDS NIH HHS [K23-NS02189, NS60941] NR 64 TC 165 Z9 166 U1 0 U2 13 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD NOV PY 2001 VL 14 IS 3 BP 129 EP 139 DI 10.1002/hbm.1047 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 485TN UT WOS:000171780100001 PM 11559958 ER PT J AU Pfefer, TJ Schomacker, KT Ediger, MN Nishioka, NS AF Pfefer, TJ Schomacker, KT Ediger, MN Nishioka, NS TI Light propagation in tissue during fluorescence spectroscopy with single-fiber probes SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE computational modeling; fiberoptic; fluorescence spectroscopy; Monte Carlo ID LASER-INDUCED FLUORESCENCE; HUMAN COLON TISSUE; IN-VIVO; TURBID MEDIA; SPECTRAL-CHARACTERIZATION; PHOTODYNAMIC THERAPY; BARRETTS-ESOPHAGUS; OPTICAL-PROPERTIES; AUTOFLUORESCENCE; MODEL AB Fluorescence spectroscopy systems designed for clinical use commonly employ fiberoptic probes to deliver excitation light to a tissue site and collect remitted fluorescence. Although a wide variety of probes have been implemented, there is little known about the influence of probe design on light propagation and the origin of detected signals. In this study, we examined the effect of optical fiber diameter, probe-tissue spacing and numerical aperture on light propagation during fluorescence spectroscopy with a single-fiber probe. A Monte Carlo model was used to simulate light transport in tissue. Two distinct sets of excitation-emission wavelength pairs were studied (337/450 nm and 400/630 nm). Simulation results indicated that increasing fiber diameter or fiber-tissue spacing increased the mean excitation-emission photon pair pathlength and produced a transition from high selectivity for superficial fluorophores to a more homogeneous probing with depth. Increasing numerical aperture caused an increase in signal intensity, but axial emission profiles and pathlengths were not significantly affected for numerical aperture values less than 0.8. Tissue optics mechanisms and implications for probe design are discussed. This study indicates that single-fiber probe parameters can strongly affect fluorescence detection and should be considered in the design of optical diagnostic devices. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RI Pfefer, Josh/I-9055-2012 NR 40 TC 39 Z9 39 U1 0 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD NOV-DEC PY 2001 VL 7 IS 6 BP 1004 EP 1012 AR PII S1077-260X(01)11251-7 DI 10.1109/2944.983306 PG 9 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 523BM UT WOS:000173931500021 ER PT J AU Boas, DA Brooks, DH Miller, EL DiMarzio, CA Kilmer, M Gaudette, RJ Zhang, Q AF Boas, DA Brooks, DH Miller, EL DiMarzio, CA Kilmer, M Gaudette, RJ Zhang, Q TI Imaging the body with diffuse optical tomography SO IEEE SIGNAL PROCESSING MAGAZINE LA English DT Review ID PHOTON-DENSITY WAVES; BORN ITERATIVE METHOD; TURBID MEDIA; SCATTERING MEDIA; HUMAN BRAIN; SIMULTANEOUS RECONSTRUCTION; MULTIPLE-SCATTERING; BIOLOGICAL TISSUES; RADIATIVE-TRANSFER; PULSE OXIMETRY C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northeastern Univ, Biomed Signal Proc Lab, Boston, MA 02115 USA. Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Tufts Univ, Dept Math, Medford, MA 02155 USA. Agilent Technol, Loveland, CO USA. RP Boas, DA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Miller, Eric/B-2546-2008; Magazine, Signal Processing/E-9947-2015 OI Miller, Eric/0000-0002-3156-6002; NR 113 TC 345 Z9 354 U1 5 U2 34 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1053-5888 J9 IEEE SIGNAL PROC MAG JI IEEE Signal Process. Mag. PD NOV PY 2001 VL 18 IS 6 BP 57 EP 75 DI 10.1109/79.962278 PG 19 WC Engineering, Electrical & Electronic SC Engineering GA 486VC UT WOS:000171836800008 ER PT J AU Goulder, PJR Pasquier, C Holmes, EC Liang, B Tang, YH Izopet, J Saune, K Rosenberg, ES Burchett, SK McIntosh, K Barnardo, M Bunce, M Walker, BD Brander, C Phillips, RE AF Goulder, PJR Pasquier, C Holmes, EC Liang, B Tang, YH Izopet, J Saune, K Rosenberg, ES Burchett, SK McIntosh, K Barnardo, M Bunce, M Walker, BD Brander, C Phillips, RE TI Mother-to-child transmission of HIV infection and CTL escape through HLA-A2-SLYNTVATL epitope sequence variation SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 3rd International Meeting on Immunological Correlates of Protection from HIV Infection and Disease CY NOV 30-DEC 03, 2000 CL LEVANTE, ITALY SP European Unions Qual Life & Management Living Resource Programme, NIH, Off AIDS Res, SmithKline Beecham Biol, Merck Res Labs, WHO, AIDS DE vertical transmission; escape; CTL; phylogenetic tree; Gag mutations ID HUMAN-IMMUNODEFICIENCY-VIRUS; LYMPHOCYTE RESPONSES; HETEROSEXUAL TRANSMISSION; VIRAL LOAD; TYPE-1; SELECTION; AIDS; PEPTIDES; RISK; IMMUNODOMINANT AB Cytotoxic T lymphocytes (CTL) play a central role in containment of HIV infection. Evasion of the immune response by CTL escape is associated with progression to disease. It is therefore hypothesised that transmitted viruses encode escape mutations within epitopes that are required for successful control of viraemia. In order to test this hypothesis, escape through the dominant HLA-A2-restricted CTL epitope SLYNTVATL (p17 Gag residues 77-85 SL9) in the setting of mother-to-child-transmission (MTCT) was investigated. Initial data from two families in which the HIN-infected mother expressed HLA-A*0201 and had transmitted the virus to other family members were consistent with this hypothesis. In addition, analysis of the gag sequence phylogeny in one family demonstrated that CTL escape variants can be successfully transmitted both horizontally and vertically. To test the hypothesis further, a larger cohort of transmitting mothers (n = 8) and non-transmitters (n = 14) were studied. Variation within the SL9 epitope was associated with expression of HLA-A2 (P = 0.04) but overall no clear link between variation from the SL9 consensus sequence and MTCT was established. However, the high level of background diversity within p17 Gag served to obscure any possible association between escape and MTCT. In conclusion, these studies highlighted the obstacles to demonstrating CTL escape arising at this particular epitope. Alternative strategies likely to be more definitive are discussed. (C) 2001 Published by Elsevier Science B.V. C1 John Radcliffe Hosp, Nuffield Dept Med, Dept Paediat, Oxford OX3 9DU, England. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Toulouse Univ Hosp, Dept Virol, Toulouse, France. Univ Oxford, Dept Zool, Oxford OX3 8FH, England. Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. Churchill Hosp, Oxford Transplant Ctr, Oxford OX3 7LJ, England. RP Goulder, PJR (reprint author), John Radcliffe Hosp, Nuffield Dept Med, Dept Paediat, Level 7,Room 7615, Oxford OX3 9DU, England. RI IZOPET, Jacques/L-5756-2014; Saune, Karine/K-4509-2014; OI Holmes, Edward/0000-0001-9596-3552 FU NIAID NIH HHS [AI 01541, AI28568, AI30914, AI46995] NR 35 TC 33 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD NOV 1 PY 2001 VL 79 IS 1-2 BP 109 EP 116 DI 10.1016/S0165-2478(01)00272-3 PG 8 WC Immunology SC Immunology GA 489PP UT WOS:000172000500016 PM 11595297 ER PT J AU Mattos-Graner, RO Jin, S King, WF Chen, T Smith, DJ Duncan, MJ AF Mattos-Graner, RO Jin, S King, WF Chen, T Smith, DJ Duncan, MJ TI Cloning of the Streptococcus mutans gene encoding glucan binding protein B and analysis of genetic diversity and protein production in clinical isolates SO INFECTION AND IMMUNITY LA English DT Article ID WATER-INSOLUBLE GLUCAN; GRAM-POSITIVE BACTERIA; LISTERIA-MONOCYTOGENES; SEQUENCE-ANALYSIS; BIOFILM FORMATION; SURFACE-PROTEINS; SEROTYPE-C; CARIES; GLUCOSYLTRANSFERASE; IDENTIFICATION AB Streptococcus mutans, the primary etiological agent of dental caries, produces several activities that promote its accumulation within the dental biofilm. These include glucosyltransferases, their glucan products, and proteins that bind glucan. At least three glucan binding proteins have been identified, and GbpB, the protein characterized in this study, appears to be novel. The gbpB gene was cloned and the predicted protein sequence contained several unusual features and shared extensive homology with a putative peptidoglycan hydrolase from group B streptococcus. Examination of gbpB genes from clinical isolates of S. mutans revealed that DNA polymorphisms, and hence amino acid changes, were limited to the central region of the gene, suggesting functional conservation within the amino and carboxy termini of the protein. The GbpB produced by clinical isolates and laboratory strains showed various distributions between cells and culture medium, and amounts of protein produced by individual strains correlated positively with their ability to grow as biofilms in an in vitro assay. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. RI Mattos-Graner, Renata/C-9410-2012 OI Mattos-Graner, Renata/0000-0001-8309-8135 FU NIDCR NIH HHS [R37 DE-06153, R37 DE006153] NR 35 TC 66 Z9 71 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2001 VL 69 IS 11 BP 6931 EP 6941 DI 10.1128/IAI.69.11.6931-6941.2001 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 485DX UT WOS:000171739200046 PM 11598068 ER PT J AU Nickerson, CA Goodwin, TJ Terlonge, J Ott, CM Buchanan, KL Uicker, WCD Emami, K LeBlanc, CL Ramamurthy, R Clarke, MS Vanderburg, CR Hammond, T Pierson, DL AF Nickerson, CA Goodwin, TJ Terlonge, J Ott, CM Buchanan, KL Uicker, WCD Emami, K LeBlanc, CL Ramamurthy, R Clarke, MS Vanderburg, CR Hammond, T Pierson, DL TI Three-dimensional tissue assemblies: Novel models for the study of Salmonella enterica serovar typhimurium pathogenesis SO INFECTION AND IMMUNITY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; FLUID SECRETION; BACTERIAL INVASION; MOLECULAR-BASIS; HOST-CELL; APOPTOSIS; INHIBITION; INDUCTION; VIRULENCE; PROTEIN AB The lack of readily available experimental systems has limited knowledge pertaining to the development of Salmonella-induced gastroenteritis and diarrheal disease in humans. We used a novel low-shear stress cell culture system developed at the National Aeronautics and Space Administration in conjunction with cultivation of three-dimensional (3-D) aggregates of human intestinal tissue to study the infectivity of Salmonella enterica serovar Typhimurium for human intestinal epithelium. Immunohistochemical characterization and microscopic analysis of 3-D aggregates of the human intestinal epithelial cell line Int-407 revealed that the 3-D cells more accurately modeled human in vivo differentiated tissues than did conventional monolayer cultures of the same cells. Results from infectivity studies showed that Salmonella established infection of the 3-D cells in a much different manner than that observed for monolayers. Following the same time course of infection with Salmonella, 3-D Int-407 cells displayed minimal loss of structural integrity compared to that of Int-407 monolayers. Furthermore, Salmonella exhibited significantly lower abilities to adhere to, invade, and induce apoptosis of 3-D Int-407 cells than it did for infected Int-407 monolayers. Analysis of cytokine expression profiles of 3-D Int-407 cells and monolayers following infection with Salmonella revealed significant differences in expression of interleukin 1 alpha- (IL-1 alpha), IL-1 beta, IL-6, IL-1Ra, and tumor necrosis factor alpha mRNAs between the two cultures. In addition, uninfected 3-D Int-407 cells constitutively expressed higher levels of transforming growth factor beta1 mRNA and prostaglandin E-2 than did uninfected Int-407 monolayers. By more accurately modeling many aspects of human in vivo tissues, the 3-D intestinal cell model generated in this study offers a novel approach for studying microbial infectivity from the perspective of the host-pathogen interaction. C1 Tulane Univ, Sch Med, Dept Microbiol & Immunol, Program Mol Pathogenesis & Immun, New Orleans, LA 70112 USA. NASA, Life Sci Res Labs, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. NASA, EASI Wyle Labs, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. Univ Space Res Assoc, Div Space Life Sci, Houston, TX 77058 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tulane Univ, Med Ctr, Nephrol Sect, New Orleans, LA 70112 USA. RP Nickerson, CA (reprint author), Tulane Univ, Sch Med, Dept Microbiol & Immunol, Program Mol Pathogenesis & Immun, SL38,1430 Tulane Ave, New Orleans, LA 70112 USA. NR 47 TC 83 Z9 85 U1 2 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2001 VL 69 IS 11 BP 7106 EP 7120 DI 10.1128/IAI.69.11.7106-7120.2001 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 485DX UT WOS:000171739200065 PM 11598087 ER PT J AU Small, GW Chen, ST Komo, S Ercoli, L Miller, K Siddarth, P Kaplan, A Dorsey, D Lavretsky, H Saxena, S Bookheimer, SY AF Small, GW Chen, ST Komo, S Ercoli, L Miller, K Siddarth, P Kaplan, A Dorsey, D Lavretsky, H Saxena, S Bookheimer, SY TI Memory self-appraisal and depressive symptoms in people at genetic risk for Alzheimer's disease SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE subjective memory; apolipoprotein E-4; depressive symptoms; memory self-appraisal; age-related cognitive decline; memory complaint ID LATE-ONSET DEPRESSION; LATE-LIFE DEPRESSION; E ALLELE EPSILON-4; APOLIPOPROTEIN-E; OLDER ADULTS; FUNCTIONING QUESTIONNAIRE; COGNITIVE CHANGE; ASSOCIATION; COMMUNITY; PERFORMANCE AB Objective A previous study found that subjective memory loss in middle-aged and older persons is associated with the major genetic risk for Alzheimer's disease, the apolipoprotein E-4 (APOE-4) allele. No previous study has focused on subjective memory complaints and depressive symptoms in the same subject population at genetic risk for Alzheimer's disease. Method Sixty-six persons (mean age = 64 years, range = 43 to 82 years) without major depression or dementia but with mild age-related memory complaints were rated for severity of depressive symptoms, using the Hamilton Depression Rating Scale, and assessed for the presence of the APOE-4 allele. Severity of subjective memory loss was assessed using the Memory Functioning Questionnaire, which measures four memory domains: frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics usage. Results Depressive symptoms were significantly associated with subjective memory loss in subjects without the APOE-4 allele, for retrospective functioning (perceived change in memory) and mnemonics usage, but not in APOE-4 carriers. The same significant associations were found when the analysis was limited to the 44 subjects in the mid-age range (55-74 years), wherein APOE-4 confers its greatest effects on risk for Alzheimer's disease. Conclusions These results confirm that mild depressive symptoms are related to subjective memory loss, but for some forms of memory complaint, the relationship holds true only for people without the major known genetic risk for Alzheimer's disease. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Alzheimers Dis Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Aging, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Small, GW (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 760 Westwood Plaza,Room 88-201, Los Angeles, CA 90024 USA. RI Lavretsky, Helen/M-5711-2015 OI Lavretsky, Helen/0000-0001-9990-5085 FU CSR NIH HHS [RG2-96-051]; NCRR NIH HHS [M01 RR00856-21]; NIA NIH HHS [AG11268, AG05128, AG10123, AG13308]; NIMH NIH HHS [MH52453]; NINDS NIH HHS [NS26630, NS31153] NR 31 TC 21 Z9 21 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD NOV PY 2001 VL 16 IS 11 BP 1071 EP 1077 DI 10.1002/gps.481 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 494RW UT WOS:000172300500009 PM 11746653 ER PT J AU Colevas, AD Read, R Thornhill, J Adak, S Tishler, R Busse, P Li, Y Posner, M AF Colevas, AD Read, R Thornhill, J Adak, S Tishler, R Busse, P Li, Y Posner, M TI Hypothyroidism incidence after multimodality treatment for stage III and IV squamous cell carcinomas of the head and neck SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE hypothyroidism; thyroid; radiation; thyroid-stimulating hormone ID INDUCTION CHEMOTHERAPY; THYROID ABNORMALITIES; CANCER; FLUOROURACIL; LEUCOVORIN; CISPLATIN; RADIATION; DOCETAXEL; TRIAL AB Purpose: Treatment of head-and-neck cancer patients with surgery, radiotherapy (RT), and chemotherapy has been associated with posttherapy hypothyroidism (HT). We evaluated the rate of posttherapy HT in patients with locally advanced squamous cell carcinoma of the head and neck, treated with multimodality therapy to determine which factors might predict this condition and at what interval the condition developed. Methods: We reviewed the prospectively collected thyroid function data of patients treated with sequential chemotherapy, RT, and neck dissection. The incidence of posttherapy HT was estimated. The patients tumor, and treatment factors possibly associated with HT were evaluated. Results: Of 203 patients, 118 had data adequate for evaluation. HT developed in 45% at a median of 24.4 months after therapy. HT occurred in 14% and 27% of patients at 6 months and 1 year after treatment, respectively. Univariate and multivariate analyses of sex, age, RT dose, RT fractionation, T and N stage, tumor site, and neck dissection failed to identify a clinically relevant risk factor. Conclusions: A high number of patients undergoing aggressive organ-sparing multimodality therapy for advanced squamous cell carcinoma of the head and neck are at risk for subsequent HT. We recommend that all patients definitively irradiated to the head and neck region undergo frequent serum thyroid-stimulating hormone screening for HT, beginning 6 months after RT. (C) 2001 Elsevier Science Inc. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Colevas, AD (reprint author), NCI, Canc Therapy Evaluat Program, DCTD, Invest Drug Branch, Execut Plaza N,Room 7131,6130 Execut Blvd, Rockville, MD 20852 USA. OI Thornhill, John/0000-0002-2923-0059 NR 17 TC 44 Z9 44 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 NOV 1 PY 2001 VL 51 IS 3 BP 599 EP 604 DI 10.1016/S0360-3016(01)01688-1 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 487TX UT WOS:000171892800004 PM 11597798 ER PT J AU Schmahmann, JD AF Schmahmann, JD TI The cerebrocerebellar system: anatomic substrates of the cerebellar contribution to cognition and emotion SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Review ID POSTERIOR PARIETAL CORTEX; FRONTAL EYE FIELD; FASTIGIAL NUCLEUS PROJECTIONS; SUPERIOR TEMPORAL SULCUS; RHESUS-MONKEY; EFFERENT CONNECTIONS; CINGULATE CORTEX; MACAQUE MONKEY; BASIS PONTIS; NEUROPSYCHOLOGICAL CONSEQUENCES AB The contribution of the cerebellum to the modulation of cognition and emotion is facilitated by the connections between the cerebellum and brain structures known to be associated with a wide array of non-motor behaviors. The cerebellum has interconnections with brainstem and thalamic reticular systems that subserve arousal. Autonomic activity is supported by the reciprocal interconnections with the hypothalamus. Limbic and paralimbic connections include the hypothalamus, septal region, hippocampus, and cingulate gyrus. Associative connections consist of both feedforward and feedback limbs. The basilar pons receives inputs from the prefrontal, posterior parietal, superior temporal, parahippocampal, and cingulate cortices, as well as from the sensorimotor cortices. This information is conveyed from the pons to cerebellum, before it is relayed back via thalamus to the associative and paralimbic regions of the cerebral cortex. The anatomical arrangement of segregated loops of cerebral cortical connections stands in contrast to the cerebellar cortical architecture that is essentially uniform. This has theoretical and clinical ramifications. It is the anatomical basis for the dysmetria of thought hypothesis that postulates a universal cerebellar transform, in which the cerebellum performs its unique computation in a topographically precise manner on diverse streams of information relating to almost all aspects of behavior including cognition and emotion. It provides an anatomic basis for the observations of cerebellar activation by cognitive and affective paradigms in functional neuroimaging experiments. It helps explain the clinical phenomena that characterize the cerebellar cognitive affective syndrome, and it provides an anatomic basis for a causal relationship between cerebellar pathology and psychiatric and neurobehavioral conditions. Knowledge of these anatomical pathways is critical to the further development of hypotheses, experimental approaches, and clinical questions that can advance the understanding of the contribution of the cerebellum to cognition and to disorders of intellect and emotion. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Burnham 823,Fruit St, Boston, MA 02114 USA. NR 156 TC 47 Z9 48 U1 1 U2 11 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD NOV PY 2001 VL 13 IS 4 BP 247 EP 260 DI 10.1080/09540260120082092 PG 14 WC Psychiatry SC Psychiatry GA 490UR UT WOS:000172071000003 ER PT J AU Schmahmann, JD AF Schmahmann, JD TI The cerebellar cognitive affective syndrome: clinical correlations of the dysmetria of thought hypothesis SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Article ID POSTERIOR-FOSSA TUMORS; DEFICIT HYPERACTIVITY DISORDER; POSITRON-EMISSION-TOMOGRAPHY; WHOLE-BRAIN RADIOTHERAPY; SUBSEQUENT DYSARTHRIA; MENTAL SKILLS; CHILDREN; MUTISM; CONTRIBUTES; ATTENTION AB The description of deficits in higher order behaviors in patients with focal cerebellar lesions has provided pivotal clinical corroboration of a cerebellar role in cognition and emotion. This paper reviews the principal observations of the cerebellar cognitive affective syndrome (CCAS) of Schmahmann & Sherman (1998) in both adults and children, namely deficits in executive, visual-spatial, linguistic and affective behaviors. Postoperative mutism and personality changes that characterize the posterior fossa syndrome, other reports describing an association between cerebellar abnormalities and intellectual deficits and psychotic behaviors, and reports of cerebellar pathology in traditionally psychiatric diseases including schizophrenia and autism are discussed. These higher order cognitive/emotional/ psychotic deficits are considered to be clinical manifestations of the dysmetria of thought hypothesis (Schmahmann, 1991) that addresses the fundamental contribution of the cerebellum to nervous system function. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Burnham 823,Fruit St, Boston, MA 02114 USA. NR 73 TC 24 Z9 25 U1 2 U2 9 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD NOV PY 2001 VL 13 IS 4 BP 313 EP 322 DI 10.1080/09540260120082164 PG 10 WC Psychiatry SC Psychiatry GA 490UR UT WOS:000172071000010 ER PT J AU Joussen, AM Huang, S Poulaki, V Camphausen, K Beecken, WD Kirchhof, B Adamis, AP AF Joussen, AM Huang, S Poulaki, V Camphausen, K Beecken, WD Kirchhof, B Adamis, AP TI In vivo retinal gene expression in early diabetes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PROTEIN-KINASE-C; NITRIC-OXIDE; INDUCED APOPTOSIS; CELLS; ACTIVATION; PHOSPHORYLATION; PERICYTES; INDUCTION; ADENOSINE AB Purpose. Studies have demonstrated a causal role for specific molecules in the pathogenesis of diabetic retinopathy. Among the implicated mediators are growth factors such as vascular endothelial growth factor (VEGF) as well as adhesion molecules and proliferation- and apoptosis-related genes. However, a coordinated large-scale investigation of gene expression in the diabetic retina has not yet been reported. Here the retinal gene expression profile of diabetic and nondiabetic animals using cDNA microarrays were analyzed and compared. Methods. Long-Evans rats were made diabetic with streptozotocin. Retinal gene expression was analyzed over 3 weeks using high-density nylon filter-based cDNA arrays. Genes were sorted into clusters according to their temporal expression profiles. They were also grouped according to their potential pathophysiological significance. The in vivo gene expression profiles of selected genes were verified via RNase protection assay. Results. The rat GeneFilter contains a total of 5147 genes, of which 1691 are known genes and 3456 are expressed sequence tags (ESTs). On day 3, the expression of 27 known genes was increased by more than twofold. On days 7 and 21, the corresponding numbers were 60 and 12, respectively. A transient upregulation (>2-fold) in expression was seen in 627 of 5147 total genes. A subset of 926 genes exhibited a modest (<2-fold) decrease in expression. No genes showed a greater than twofold decrease in expression. Overall, the identity of the genes that were upregulated suggests that the response of the retina to the diabetic challenge contains an inflammatory component. Moreover, most regulatory activity occurs during the first week of diabetes. Conclusions. The development of a rational therapy for diabetic retinopathy will be assisted by detailed knowledge regarding the molecular pathophysiology of the disease. Here, an expression profile of an underlying retinal inflammatory process in early diabetes was extracted. Beyond providing insight into the general nature of the response to a pathogenic challenge, gene expression profiling may also allow the efficient identification of potential drug targets and markers for monitoring the course of disease. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Surg Res Labs, Boston, MA USA. Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, Cologne, Germany. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Res Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY11627, R01 EY12611] NR 77 TC 59 Z9 65 U1 0 U2 1 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 NOV PY 2001 VL 42 IS 12 BP 3047 EP 3057 PG 11 WC Ophthalmology SC Ophthalmology GA 488ZK UT WOS:000171967100045 PM 11687554 ER PT J AU Robinson-Whelen, S Tada, Y MacCallum, RC McGuire, L Kiecolt-Glaser, JK AF Robinson-Whelen, S Tada, Y MacCallum, RC McGuire, L Kiecolt-Glaser, JK TI Long-term caregiving: What happens when it ends? SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID BECK DEPRESSION INVENTORY; OLDER-ADULTS; CHRONIC STRESS; BEREAVEMENT SUPPORT; ALZHEIMERS-DISEASE; SOCIAL SUPPORT; FAMILY; SYMPTOMS; DEMENTIA; DEATH AB Data from a longitudinal study were used to examine what happens to caregivers in the years after their cognitively impaired spouse dies. Comparisons of 42 current caregivers, 49 former caregivers, and 52 noncaregivers over a 4-year period showed that former caregivers did not improve on several measures of psychological well-being. Although former caregivers experienced decreases in stress and negative affect, their scores on depression, loneliness, and positive affect did not rebound to levels comparable to noncaregivers and, in fact, remained similar to those of current caregivers up to 3 years after caregiving had ceased. The most consistent predictors of postcaregiving outcomes were social support and intrusive-avoidant thinking about caregiving. The data suggest that some consequences of long-term caregiving may be long-term as well. The needs of former spousal caregivers warrant greater attention both in research and in practice. C1 Houston VAMC, Ctr Excellence Healthy Aging Disabil, Houston, TX 77030 USA. Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA. Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. RP Robinson-Whelen, S (reprint author), Houston VAMC, Ctr Excellence Healthy Aging Disabil, 153, Houston, TX 77030 USA. EM susanrw@bcm.tmc.edu RI Kiecolt-Glaser, Janice/A-3236-2009 OI Kiecolt-Glaser, Janice/0000-0003-4900-9578 FU NIA NIH HHS [P01 AG11585]; NIMH NIH HHS [R01 MH50538, K02 MH01467, R37 MH42096] NR 58 TC 58 Z9 62 U1 3 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2001 VL 110 IS 4 BP 573 EP 584 DI 10.1037//0021-843X.110.4.573 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 491KK UT WOS:000172107400008 PM 11727947 ER PT J AU Weinger, K O'Donnell, KA Ritholz, MD AF Weinger, K O'Donnell, KA Ritholz, MD TI Adolescent views of diabetes-related parent conflict and support: A focus group analysis SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescent; type 1 diabetes; focus groups; diabetes-related parent conflict; diabetes-related parent support ID LONGITUDINAL FOLLOW-UP; METABOLIC CONTROL; GLYCEMIC CONTROL; MELLITUS; FAMILY; ADHERENCE; CHILDREN; MANAGEMENT; CARE; INTERVENTION AB Purpose: To increase understanding of adolescent-parent diabetes-related conflicts and supports in the management of type 1 diabetes by means of a focus group research approach. Methods: Twenty-four adolescents (10 boys and 14 girls, age 13-15 years; 97% white) participated in three same-sex focus groups at two diabetes summer camps. The focus group leader used a prepared set of open-ended questions to guide the 90-minute sessions. Sessions were tape-recorded, transcribed, and analyzed by a set procedure for qualitative analysis to identify the adolescents' perspectives on parent-adolescent sources of diabetes-related conflict and support. Results: Adolescents reported the following sources of diabetes-related conflict: parental worry and intrusive behaviors; parental lack of understanding and blaming behaviors, and the parents focus on the future vs. the adolescent focus on the present. With regard to diabetes-related support, the teens identified parental understanding of the demands of diabetes and parental provision of reassurance about their child's illness and normative functioning. Conclusions: Adolescents' perceptions of parental worry, lack of understanding, and resulting intrusive and blaming behaviors are major areas of conflict that need to be addressed in the management of type 1 diabetes. (C) Society for Adolescent Medicine, 2001. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Behav & Mental Hlth, Boston, MA 02215 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. Dartmouth Coll Sch Med, Hanover, NH USA. RP Weinger, K (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Behav & Mental Hlth, Room 350,1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK042315]; NINR NIH HHS [F32 NR007157, F32 NR07157]; PHS HHS [42315] NR 38 TC 52 Z9 56 U1 5 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD NOV PY 2001 VL 29 IS 5 BP 330 EP 336 DI 10.1016/S1054-139X(01)00270-1 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 491LH UT WOS:000172109500005 PM 11691594 ER PT J AU Amory, JK Anawalt, BD Bremner, WJ Matsumoto, AM AF Amory, JK Anawalt, BD Bremner, WJ Matsumoto, AM TI Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: Implications for male contraceptive development SO JOURNAL OF ANDROLOGY LA English DT Article DE contraception; gonadotropins; azoospermia ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; SPERM PRODUCTION; SPERMATOGENESIS; ENANTHATE; COMBINATION; SUPPRESSION; EFFICACY AB Weekly intramuscular administration of testosterone esters such as testosterone enanthate (TE) suppresses gonadotropins and spermatogenesis and has been studied as a male contraceptive. For unknown reasons, however, some men fail to achieve azoospermia with such regimens. We hypothesized that either 1) daily circulating serum fluoroimmunoreactive gonadotropins were higher or testosterone levels were lower during the weekly injection interval, or 2) monthly circulating bioactive gonadotropin levels were higher in nonazoospermic men. We therefore analyzed daily testosterone and fluoroimmunoreactive gonadotropin levels as well as pooled monthly bioactive and fluoroimmunoreactive gonadotropin levels in normal men receiving chronic TE injections and correlated these levels with sperm production. After a 3-month control period, 51 normal men were randomly assigned to receive intramuscular TE at 25 mg (n = 10), 50 mg (n = 9), 100 mg (n = 10), 300 mg (n = 10), or placebo (n = 12) weekly for 6 months. After 5 months of testosterone administration, morning testosterone and fluoroimmunoreactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured daily for a 1-week period between TE injections. In addition, fluoroimmunoreactive and bioactive FSH and LH levels were measured in pooled monthly blood samples drawn just before the next TE injection. In the 100-mg and 300-mg TE groups, mean monthly fluoroimmunoreactive FSH and LH levels were suppressed by 86%-97%, bioactive FSH and LH levels by 62%-80%, and roughly half the subjects became azoospermic. In the 1-week period of month 6, daily testosterone levels between TE injections were within the normal range in men receiving placebo, or 25 or 50 mg of weekly TE, but were significantly elevated in men receiving 100 or 300 mg of weekly TE. At no point during treatment, however, were there significant differences in daily testosterone or fluoroimmunoreactive gonadotropin levels, or monthly bioactive gonadotropin levels between men achieving azoospermia and those with persistent spermatogenesis. This study, therefore, demonstrates that neither monthly nor daily differences in serum testosterone, or fluoroimmunoreactive or bioactive gonadotropins explain why some men fail to completely suppress their sperm counts to zero with weekly TE administration. Innate differences in the testicle's ability to maintain spermatogenesis in a low-gonadotropin environment may explain persistent spermatogenesis in some men treated with androgen-based contraceptive regimens. C1 Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Populat Ctr Res Reprod, Seattle, WA USA. Univ Washington, Clin Res Ctr, Seattle, WA 98195 USA. RP Univ Washington, Sch Med, Dept Med, Box 356429,1959 NE Pacific St, Seattle, WA 98195 USA. EM jamory@u.washington.edu FU NCRR NIH HHS [RR-37]; NICHD NIH HHS [P-50-HD-12629] NR 18 TC 27 Z9 27 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 EI 1939-4640 J9 J ANDROL JI J. Androl. PD NOV-DEC PY 2001 VL 22 IS 6 BP 1053 EP 1060 PG 8 WC Andrology SC Endocrinology & Metabolism GA 487FU UT WOS:000171863600016 PM 11700852 ER PT J AU Cradock, J Young, AS Sullivan, G AF Cradock, J Young, AS Sullivan, G TI The accuracy of medical record documentation in schizophrenia SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH LA English DT Article ID MENTAL-HEALTH; RATING-SCALE; QUALITY; CARE; DEPRESSION; AGREEMENT; SERVICES AB Medical records are commonly used to measure quality of care. However, little is known about how accurately they reflect patients' clinical condition. Even less is understood about what influences the accuracy of provider's documentation and whether patient characteristics impact documentation habits. Discrepancies between symptoms and side effects evaluated by direct assessment and medical records were examined for 224 patients with schizophrenia at two public mental health clinics. Multivariate regression was used to study the relationship between patient, provider; and treatment characteristics and documentation accuracy. Overall, documentation of symptoms and side effects was frequently absent. Documentation varied substantially between clinics, and it was generally less likely for patients who were severely ill, black, or perceived as noncompliant. The accuracy and consistency of medical record documentation should be demonstrated before using it to evaluate care at public mental health clinics. C1 W Lost Angeles Vet Healthcare Ctr, VISN MIRECC 22, Los Angeles, CA 90073 USA. Dept Vet Affairs, VISN MIRECC 22, Hlth Serv Unit, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Dept Vet Affairs, VISN MIRECC 16, Little Rock, AR USA. RP Cradock, J (reprint author), W Lost Angeles Vet Healthcare Ctr, VISN MIRECC 22, 11301 Wilshire Blvd,Bldg 210A, Los Angeles, CA 90073 USA. RI Young, Alexander/A-1523-2009 OI Young, Alexander/0000-0002-9367-9213 FU NIMH NIH HHS [P50 MH-54623] NR 28 TC 34 Z9 34 U1 0 U2 0 PU ASPEN PUBL INC PI GAITHERSBURG PA 200 ORCHARD RIDGE DR, STE 200, GAITHERSBURG, MD 20878 USA SN 1094-3412 J9 J BEHAV HEALTH SER R JI J. Behav. Health Serv. Res. PD NOV PY 2001 VL 28 IS 4 BP 456 EP 465 DI 10.1007/BF02287775 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 492NX UT WOS:000172175400006 PM 11732247 ER PT J AU Katz, JN Losina, E Barrett, J Phillips, CB Mahomed, NN Lew, RA Guadagnoli, E Harris, WH Poss, R Baron, JA AF Katz, JN Losina, E Barrett, J Phillips, CB Mahomed, NN Lew, RA Guadagnoli, E Harris, WH Poss, R Baron, JA TI Association between hospital and surgeon procedure volume and outcomes of total hip replacement in the United States Medicare population SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID NEW-YORK-STATE; CORONARY ANGIOPLASTY VOLUME; BYPASS GRAFT-SURGERY; SHORT-TERM MORTALITY; KNEE REPLACEMENT; ELDERLY PATIENTS; SURGICAL VOLUME; REGIONALIZATION; COMPLICATIONS; OPERATIONS AB Background: The mortality and complication rates of many surgical procedures are inversely related to hospital procedure volume. The objective of this study was to determine whether the volumes of primary and revision total hip replacements performed at hospitals and by surgeons are associated with rates of mortality and complications. Methods: We analyzed claims data of Medicare recipients who underwent elective primary total hip replacement (58,521 procedures) or revision total hip replacement (12,956 procedures) between July 1995 and June 1996. We assessed the relationship between surgeon and hospital procedure volume and mortality, dislocation, deep infection, and pulmonary embolus in the first ninety days postoperatively. Analyses were adjusted for age, gender, arthritis diagnosis, comorbid conditions, and income. Analyses of hospital volume were adjusted for surgeon volume, and analyses of surgeon volume were adjusted for hospital volume. Results: Twelve percent of all primary total hip replacements and 49% of all revisions were performed in centers in which ten or fewer of these procedures were carried out in the Medicare population annually. In addition, 52% of the primary total hip replacements and 77% of the revisions were performed by surgeons who carried out ten or fewer of these procedures annually. Patients treated with primary total hip replacement in hospitals in which more than 100 of the procedures were performed per year had a lower risk of death than those treated with primary replacement in hospitals in which ten or fewer procedures were performed per year (mortality rate, 0.7% compared with 1.3%; adjusted odds ratio, 0.58; 95% confidence interval, 0.38, 0.89). Patients treated with primary total hip replacement by surgeons who performed more than fifty of those procedures in Medicare beneficiaries per year had a lower risk of dislocation than those who were treated by surgeons who performed five or fewer of the procedures per year (dislocation rate, 1.5% compared with 4.2%; adjusted odds ratio, 0.49; 95% confidence interval, 0.34, 0.69). Patients who had revision total hip replacement done by surgeons who performed more than ten such procedures per year had a lower rate of mortality than patients who were treated by surgeons who performed three or fewer of the procedures per year (mortality rate, 1.5% compared with 3.1%; adjusted odds ratio, 0.65; 95% confidence interval, 0.44, 0.96). Conclusions: Patients treated at hospitals and by surgeons with higher annual caseloads of primary and revision total hip replacement had lower rates of mortality and of selected complications. These analyses of Medicare claims are limited by a lack of key clinical information such as operative details and preoperative functional status. C1 Brigham & Womens Hosp, Robert B Bringham Multipurpose Arthrit & Musculos, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Toronto Western Hosp, Musculoskeletal Hlth & Arthrit Program, Toronto, ON M5T 2S8, Canada. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dept Med, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Family & Community Med, Hanover, NH 03755 USA. RP Katz, JN (reprint author), Brigham & Womens Hosp, Robert B Bringham Multipurpose Arthrit & Musculos, 75 Francis St, Boston, MA 02115 USA. FU AHRQ HHS [1R01 HS09775-01]; NIAMS NIH HHS [K24 AR 02123, P01 AR36308] NR 37 TC 367 Z9 373 U1 1 U2 11 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 NOV PY 2001 VL 83A IS 11 BP 1622 EP 1629 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 490YR UT WOS:000172081700003 PM 11701783 ER PT J AU Klein, RF Carlos, AS Vartanian, KA Chambers, VK Turner, RJ Phillips, TJ Belknap, JK Orwoll, ES AF Klein, RF Carlos, AS Vartanian, KA Chambers, VK Turner, RJ Phillips, TJ Belknap, JK Orwoll, ES TI Confirmation and fine mapping of chromosomal regions influencing peak bone mass in mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE bone mineral density; osteoporosis; heredity; quantitative trait; quantitative trait locus analysis ID QUANTITATIVE TRAIT LOCI; RECOMBINANT INBRED STRAINS; GENETIC DISSECTION; COMPLEX TRAITS; MINERAL DENSITY; MOUSE STRAINS; LINKAGE; QTL; OSTEOPENIA; FRACTURE AB Bone mineral density (BMD) is determined by both environmental influences and polygenic inheritance. The extreme difficulty of dissecting out environmental factors from genetic ones in humans has motivated the investigation of animal models. Previously, we used quantitative trait locus (QTL) analysis to examine peak BMD in 24 recombinant inbred (RI) mouse strains, derived from a cross between C57BL/6 (B6) and DBA/2 (D2) progenitors (RI-BXD). The distribution of BMD values among these strains indicated strong genetic influences and a number of chromosomal sites linked to BMD were identified provisionally. Using three additional independent mapping populations derived from the same progenitors, we have confirmed loci on chromosomes 1, 2, and 4, and 11 that contain genes that influence peak BMD. Using a novel fine-mapping approach (RI segregation testing [RIST]), we have substantially narrowed two of the BMD-related chromosomal regions and in the process eliminated a number of candidate genes. The homologous regions in the human genome for each of these murine QTLs have been identified in recent human genetic studies. In light of this, we believe that findings in mice should aid in the identification of specific candidate genes for study in humans. C1 Oregon Hlth Sci Univ, Dept Med, Bone & Mineral Res Unit, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Dept Med, Bone & Mineral Res Unit, Portland, OR USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Dept Behav Neurosci, Portland, OR USA. RP Klein, RF (reprint author), Oregon Hlth Sci Univ, Dept Med, Bone & Mineral Res Unit, Portland, OR 97201 USA. OI Orwoll, Eric/0000-0002-8520-7355 NR 35 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2001 VL 16 IS 11 BP 1953 EP 1961 DI 10.1359/jbmr.2001.16.11.1953 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 484NE UT WOS:000171695800003 ER PT J AU Orwoll, ES Belknap, JK Klein, RF AF Orwoll, ES Belknap, JK Klein, RF TI Gender specificity in the genetic determinants of peak bone mass SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE quantitative trait; gender; osteoporosis; bone mineral density; mouse ID QUANTITATIVE TRAIT LOCI; RECOMBINANT INBRED STRAINS; MINERAL DENSITY; OLDER WOMEN; MICE; SEX; RATS; IDENTIFICATION; LINKAGE; OSTEOPOROSIS AB Peak bone mass is a major determinant of osteoporotic fracture risk. Gender differences in peak bone mass acquisition are well recognized in humans and may account for a substantial share of the increased prevalence of fragility fractures in women compared with men. Skeletal development is regulated by both heritable and environmental factors. Experimental animal models provide a means to circumvent complicating environmental factors. In this study we examined the heritability of peak bone mineral density (BMD) in genetically distinct laboratory mouse strains raised under strict environmental control and sought to identify genetic loci that may contribute to gender differences in this skeletal phenotype. Peak whole body BMD of male and female mice from a panel of 18 recombinant inbred (RI) strains derived from a cross between C57BL/6 and DBA/2 progenitors (BXD) was measured by dual-energy X-ray absorptiometry (DXA). A, highly significant relationship existed between body weight and BMD in the BXD RI mice (r(2) = 0.25; p = 1 x 10(-43)). To allow for comparison between male and female RI strains, whole body BMD values were corrected for the influence of body weight. The distribution of weight-corrected BMD (WC-BMD) values among the strains indicated the presence of strong genetic influences in both genders, with an estimated narrow sense heritability of 45% and 22% in male and female mice, respectively. Comparison of RI strain results by two-way analysis of variance (ANOVA) revealed a significant strain-by-gender interaction (F-1,F-17,F-479 = 6.13; p < 0.0001). Quantitative trait locus (QTL) analysis of the BXD RI strain series provisionally identified nine chromosomal sites linked to peak bone mass development in males and seven regions in females. In two cases, the provisional chromosomal loci were shared between genders, but in most cases they were distinct (five female-specific QTLs and six male-specific QTLs). QTL analysis of a genetically heterogeneous F-2 population derived from the B6 and D2 progenitor strains provided additional support for the gender specificity of two loci. A significant phenotype-genotype correlation was only observed in male F-2 mice at microsatellite marker D7Mit114 on chromosome 7, and a correlation at D2Mit94 on chromosome 2 was only observed in female F-2 mice. The present data highlight the important role of gender in the genetic basis of peak bone mass in laboratory mice. Because the male phenotype is associated with considerable fracture risk reduction, an elucidation of the nature of that effect could provide the basis for novel diagnostic, preventative, or therapeutic approaches. C1 Oregon Hlth Sci Univ, Dept Med, Bone & Mineral Res Unit, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Bone & Mineral Res Unit, Dept Med, Portland, OR USA. Portland Vet Affairs Med Ctr, Dept Behav Neurosci, Portland, OR USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Orwoll, ES (reprint author), Oregon Hlth Sci Univ, Dept Med, Bone & Mineral Res Unit, Portland, OR 97201 USA. OI Orwoll, Eric/0000-0002-8520-7355 FU NIAAA NIH HHS [AA 10760]; NIAMS NIH HHS [R01 AR044659, AR 44659, R01 AR044659-08] NR 48 TC 143 Z9 145 U1 0 U2 5 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2001 VL 16 IS 11 BP 1962 EP 1971 DI 10.1359/jbmr.2001.16.11.1962 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 484NE UT WOS:000171695800004 PM 11697792 ER PT J AU Miller, SF McDonald-Smith, GP AF Miller, SF McDonald-Smith, GP TI Computer-related activities at the 2001 ABA Annual Meeting SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article C1 Wright State Univ DOS, Dayton, OH 45409 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Miller, SF (reprint author), Wright State Univ DOS, 1 Wyoming St,Suite 7000 CHE, Dayton, OH 45409 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 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD NOV-DEC PY 2001 VL 22 IS 6 BP 425 EP 428 DI 10.1097/00004630-200111000-00013 PG 4 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 606TW UT WOS:000178750500010 PM 11761395 ER PT J AU Minshew, NJ Goldstein, G AF Minshew, NJ Goldstein, G TI The pattern of intact and impaired memory functions in autism SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE Autistic Disorder; memory; learning; abstract reasoning; concept formation; information processing ID DIAGNOSTIC INTERVIEW; INFANTILE-AUTISM; CHILDREN; INDIVIDUALS; DISORDER AB A battery of tests of auditory and visual memory was used to investigate memory function in 52 high-functioning adolescents and young adults with autism and 40 group-matched normal controls. It was hypothesized that memory dysfunction is present in autism but is not modality specific and is produced by poor utilization of organizing strategies. It was therefore hypothesized that memory impairment in autism would become more prominent as task complexity was increased. The participants with autism performed as well as controls on short-term memory and paired-associate learning tasks, but performed significantly less well than controls on a list learning task. They also performed significantly more poorly on immediate and delayed recall of a story and of a complex geometric figure. On a maze learning task, their performance became progressively worse relative to controls as the complexity of the maze increased. On a series of span tasks, they did not differ from controls on letter span, but did significantly worse on word span and sentences of increasing complexity. These findings indicate a lack of modality specificity and a failure to initiate organizing strategies as evidenced by inefficiency in new learning, poor utilization of contextual cues in story and complex pattern recall, and greater impairment with increasing complexity of the material. C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Minshew, NJ (reprint author), Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St,Suite 430,Bellefield Towers Bldg, Pittsburgh, PA 15213 USA. FU NICHD NIH HHS [HD35469]; NINDS NIH HHS [NS33355] NR 36 TC 108 Z9 108 U1 1 U2 11 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD NOV PY 2001 VL 42 IS 8 BP 1095 EP 1101 DI 10.1111/1469-7610.00808 PG 7 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 515FM UT WOS:000173484800013 PM 11806691 ER PT J AU Phillips, SA Rotman-Pikielny, P Lazar, J Ando, S Hauser, P Skarulis, MC Brucker-Davis, F Yen, PM AF Phillips, SA Rotman-Pikielny, P Lazar, J Ando, S Hauser, P Skarulis, MC Brucker-Davis, F Yen, PM TI Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RECEPTOR-BETA GENE; GENERALIZED RESISTANCE; TRANSCRIPTIONAL REGULATION; BINDING DOMAIN; LIGAND-BINDING; MUTATION; FAMILIES; MICE; EXPRESSION; PHENOTYPE AB Resistance to thyroid hormone (RTH) is a syndrome in which patients have elevated thyroid hormone (TH) levels and decreased sensitivity to its action. We describe a child with extreme RTH and a severe phenotype. A 22-month-old female presented to the NIH with goiter, growth retardation, short stature, and deafness. Additionally, the patient had hypotonia, mental retardation, visual impairment, and a history of seizures. Brain magnetic resonance imaging showed evidence of demyelination and bilateral ventricular enlargement. The patient had markedly elevated free T(3) and free T(4) levels of more than 2000 pg/dl (normal, 230-420 pg/dl) and more than 64 pmol/liter (normal, 10.3-20.6 pmol/liter), respectively, and TSH of 6.88 mU/liter (normal, 0.6-6.3 mU/liter). These are the highest TH levels reported for a heterozygous RTH patient. A T(3) stimulation test confirmed the diagnosis of RTH in the pituitary and peripheral tissues. Molecular analyses of the patient's genomic DNA by PCR identified a single base deletion in exon 10 of her TR beta gene that resulted in a frameshift and early stop codon. This, in turn, encoded a truncated receptor that lacked the last 20 amino acids. Cotransfection studies showed that the mutant TR was transcriptionally inactive even in the presence of 10(-6) M T(3) and had strong dominant negative activity over the wild-type receptor. It is likely that the severely defective TR beta mutant contributed to the extreme RTH phenotype and resistance in our patient. C1 NIDDKD, Clin Endocrinol Branch, Mol Regulat & Neuroendocrinol Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Univ Nice, Ctr Hosp, Dept Med, Nice, France. RP Yen, PM (reprint author), NIDDKD, Clin Endocrinol Branch, Mol Regulat & Neuroendocrinol Sect, NIH, Bldg 10,Room 8D12, Bethesda, MD 20892 USA. EM pauly@intra.niddk.nih.gov NR 34 TC 14 Z9 16 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5142 EP 5147 DI 10.1210/jc.86.11.5142 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600008 PM 11701667 ER PT J AU Maianu, L Keller, SR Garvey, WT AF Maianu, L Keller, SR Garvey, WT TI Adipocytes exhibit abnormal subcellular distribution and translocation of vesicles containing glucose transporter 4 and insulin-regulated aminopeptidase in type 2 diabetes mellitus: Implications regarding defects in vesicle trafficking SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUT4 GLUCOSE TRANSPORTERS; SKELETAL-MUSCLE; 3T3-L1 ADIPOCYTES; MEMBRANE AMINOPEPTIDASE; PRETRANSLATIONAL SUPPRESSION; PLASMA-MEMBRANE; ADIPOSE-CELLS; RESISTANCE; PROTEIN; OBESITY AB Insulin resistance in type 2 diabetes is due to impaired stimulation of the glucose transport system in muscle and fat. Different defects are operative in these two target tissues because glucose transporter 4 (GLUT 4) expression is normal in muscle but markedly reduced in fat. In muscle, GLUT 4 is redistributed to a dense membrane compartment, and insulin-mediated translocation to plasma membrane (PM) is impaired. Whether similar trafficking defects are operative in human fat is unknown. Therefore, we studied subcellular localization of GLUT4 and insulin-regulated aminopeptidase (IRAP; also referred to as vp165 or gp160), which is a constituent of GLUT4 vesicles and also translocates to PM in response to insulin. Subcutaneous fat was obtained from eight normoglycemic control subjects (body mass index, 29 +/- 2 kg/m(2)) and eight type 2 diabetic patients (body mass index, 30 +/- 1 kg/m(2); fasting glucose, 14 +/- 1 mm). In adipocytes isolated from diabetics, the basal 3-O-methylglucose transport rate was decreased by 50% compared with controls (7.1 +/- 2.9 vs. 14.1 +/- 3.7 mmol/mm(2) surface area/min), and there was no increase in response to maximal insulin (7.9 +/- 2.7 vs. 44.5 +/- 9.2 in controls). In membrane subfractions from controls, insulin led to a marked increase of IRAP in the PM from 0.103 +/- 0.04 to 1.00 +/- 0.33 relative units/mg protein, concomitant with an 18% decrease in low-density microsomes and no change in high-density microsomes (HDM). In type 2 diabetes, IRAP overall expression in adipocytes was similar to that in controls; however, two abnormalities were observed. First, in basal cells, IRAP was redistributed away from low-density microsomes, and more IRAP was recovered in HDM (1.2-fold) and PM (4.4-fold) from diabetics compared with controls. Second, IRAP recruitment to PM by maximal insulin was markedly impaired. GLUT4 was depleted in all membrane subfractions (43-67%) in diabetes, and there was no increase in PM GLUT4 in response to insulin. Type 2 diabetes did not affect the fractionation of marker enzymes. We conclude that in human adipocytes: 1) IRAP is expressed and translocates to PM in response to insulin; 2) GLUT4 depletion involves all membrane subfractions in type 2 diabetes, although cellular levels of IRAP are normal; and 3) in type 2 diabetes, IRAP accumulates in membrane vesicles cofractionating with HDM and PM under basal conditions, and insulin-mediated recruitment to PM is impaired. Therefore, in type 2 diabetes, adipocytes express defects in trafficking of GLUT4/IRAP-containing vesicles similar to those causing insulin resistance in skeletal muscle. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Univ Virginia, Sch Med, Dept Med, Charlottesville, VA 22908 USA. RP Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, CSB323,96 Jonathan Lucas St, Charleston, SC 29425 USA. EM garveywt@musc.edu FU NCRR NIH HHS [M01-RR-1070]; NIDDK NIH HHS [DK-25336, DK-38764] NR 43 TC 54 Z9 59 U1 0 U2 2 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5450 EP 5456 DI 10.1210/jc.86.11.5450 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600056 PM 11701721 ER PT J AU Hayes, FJ Pitteloud, N DeCruz, S Crowley, WF Boepple, PA AF Hayes, FJ Pitteloud, N DeCruz, S Crowley, WF Boepple, PA TI Importance of inhibin B in the regulation of FSH secretion in the human male SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; GONADOTROPIN-RELEASING-HORMONE; MONKEY MACACA-MULATTA; DOSE KETOCONAZOLE THERAPY; RECOMBINANT HUMAN INHIBIN; CLINICAL RESEARCH-CENTER; SEX STEROID CONTROL; FREE ALPHA-SUBUNIT; LUTEINIZING-HORMONE; FEEDBACK-CONTROL AB Regulation of FSH secretion in the male involves a complex balance between stimulation by GnRH from the hypothalamus, inhibitory feedback by sex steroids (T and E2) and inhibin B (Inh B) from the gonads, and autocrine/paracrine modulation by activin and follistatin within the pituitary. The aim of the present study was to delineate the feedback control of FSH in the human male with specific reference to the relative roles of sex steroids vs. Inh B. Two experimental human models were used: 1) normal (NL) men subjected to acute sex steroid withdrawal (-T, -E2, + Inh B), and 2) functional castrate males (-T, -E2, -Inh B). Nine NL men (age range, 25-45 yr) and three castrate males (age range, 23-47 yr) were studied. The NL men underwent acute sex steroid suppression using high dose ketoconazole (1-g loading dose, followed by 400 mg, orally, four times daily for 150 h). Gonadotropin secretion was characterized by frequent blood sampling every 10 min for 12 h at baseline and on d 3 and 6 of sex steroid ablation. In the three castrate subjects, blood sampling was performed every 5 min for 24 h 8 wk after discontinuing androgen replacement therapy. In the NL men, treatment with ketoconazole resulted in a decline to castrate levels in T (451 +/- 20 to 38 +/- 7 ng/dl; P < 0.0005) and E2 (39 +/- 4 to 15 +/- 2 pg/ml; P < 0.005) and a modest, but significant, decline in Inh B levels, which remained within the normal range (183 +/- 19 to 136 +/- 13 pg/ml; P < 0.005). This suppression of sex steroids was associated with a more marked increase in mean LH (9.5 +/- 0.9 to 24.9 +/- 2.0 IU/liter; P < 0.0001) than FSH levels (5.1 +/- 0.7 to 10.0 +/- 1.5 IU/liter; P < 0.005), with the latter not exceeding the normal adult male range. The castrate subjects had a mean T level of 66 +/- 8 ng/dl, an E2 level of 20 +/- 1 pg/ml, and undetectable Inh B levels. Despite a similar sex steroid milieu, the mean FSH levels observed in NL men after acute sex steroid ablation were approximately 6-fold lower than those seen in the castrate subjects (10.0 +/- 1.5 vs. 59.5 +/- 17.7 IU/liter; P < 0.0005). In contrast, mean LH levels in the NL men were less than 3-fold lower than those in castrate subjects (24.9 +/- 2.0 vs. 66.8 +/- 20.1 IU/liter; P < 0.005). From this human model of acute sex steroid withdrawal, we conclude that Inh B is likely to be the major feedback regulator of FSH secretion in the human male. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Fruit St, Boston, MA 02114 USA. EM hayes.frances@mgh.harvard.edu RI PITTELOUD, Nelly/K-2709-2014 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [U54 HD029164, P30 HD028138, P30-HD-28138, R01 HD015788, R01-HD-15788-15, U54 HD028138]; NIDDK NIH HHS [DK-07028-24] NR 60 TC 40 Z9 40 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2001 VL 86 IS 11 BP 5541 EP 5546 DI 10.1210/jc.86.11.5541 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 491YK UT WOS:000172137600068 PM 11701733 ER PT J AU Prasad, SR Sahani, D Saini, S AF Prasad, SR Sahani, D Saini, S TI Clinical applications of magnetic resonance cholangiopancreatography SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE magnetic resonance cholangiopancreatography; endoscopic retrograde cholangiopancreatography; biliary obstruction; pancreatic duct abnormalities ID ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; PRIMARY SCLEROSING CHOLANGITIS; MR CHOLANGIOPANCREATOGRAPHY; LAPAROSCOPIC CHOLECYSTECTOMY; SECRETIN STIMULATION; DIAGNOSTIC-ACCURACY; PANCREAS DIVISUM; BILIARY-TRACT; SPIN-ECHO; CHOLANGIOGRAPHY AB Magnetic resonance cholangiopancreatography (MRCP) is a novel imaging technique used for noninvasive work-up of patients with pancreaticobiliary disease. Magnetic resonance cholangiopancreatography is useful in the evaluation of a host of pancreaticobiliary disorders, such as congenital disorders, calculus disease, biliary strictures, sclerosing cholangitis, chronic pancreatitis, and cystic pancreatic lesions. It not only provides useful preoperative information to surgeons and gastroenterologists but also serves as a valuable tool in the assessment of postoperative pancreaticobiliary ductal anatomy. Recent refinement of techniques allows faster imaging with superior image resolution. This review summarizes the role of MRCP in clinical practice. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 37 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD NOV-DEC PY 2001 VL 33 IS 5 BP 362 EP 366 DI 10.1097/00004836-200111000-00004 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 486NM UT WOS:000171823900004 PM 11606850 ER PT J AU Rollins, BJ AF Rollins, BJ TI Chemokines and atherosclerosis: what Adam Smith has to say about vascular disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID RECEPTOR-DEFICIENT MICE; REDUCES ATHEROSCLEROSIS; MONOCYTE; ADHESION; MCP-1; INTERLEUKIN-8; ENDOTHELIUM; ABSENCE C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 23 Z9 25 U1 1 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2001 VL 108 IS 9 BP 1269 EP 1271 DI 10.1172/JCI14273 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 490KM UT WOS:000172051100006 PM 11696568 ER PT J AU Burne, MJ Daniels, F El Ghandour, A Mauiyyedi, S Colvin, RB O'Connell, MP Rabb, H AF Burne, MJ Daniels, F El Ghandour, A Mauiyyedi, S Colvin, RB O'Connell, MP Rabb, H TI Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACUTE TUBULAR-NECROSIS; ISCHEMIA/REPERFUSION INJURY; REPERFUSION INJURY; ADHESION-MOLECULES; LYMPHOCYTES; LIVER; MICE; INTERLEUKIN-10; INHIBITION; LEUKOCYTES AB Leukocytes have been implicated in the pathogenesis of ischemic acute renal failure (ARF), but the roles of the individual cell types involved are largely unknown. Recent indirect evidence suggests that T cells may play an important role in a murine model of ARF. In the current study, we found that mice deficient in T cells (nu/nu mice) are both functionally and structurally protected from postischemic renal injury. Reconstitution of nu/nu mice with wild-type T cells restored postischemic injury. We then analyzed the contribution of the individual T cell subsets to postischemic injury and found that mice deficient in CD4(+) T cells, but not mice deficient in CD8(+) T cells, were significantly protected from ARF. Direct evidence for a pathophysiologic role of the CD4(+) T cell was obtained when reconstitution of CD4-deficient mice with wild-type CD4(+) T cells restored postischemic injury. In addition, adoptive transfers of CD4(+) T cells lacking either the costimulatory molecule CD28 or the ability to produce IFN-gamma were inadequate to restore injury phenotype. These results demonstrate that the CD4(+) T cell is an important mediator of ischemic ARF, and targeting this cell may yield novel therapies. C1 Univ Minnesota, Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Rabb, H (reprint author), Johns Hopkins Univ, Sch Med, Ross Bldg,Room 970,720 Rutland Ave, Baltimore, MD 21205 USA. FU NIDDK NIH HHS [R01 DK054770, R01DK-54770] NR 24 TC 266 Z9 277 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2001 VL 108 IS 9 BP 1283 EP 1290 DI 10.1172/JCI12080 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 490KM UT WOS:000172051100010 PM 11696572 ER PT J AU Franklin, CL Gorelick, PL Riley, LK Dewhirst, FE Livingston, RS Ward, JM Beckwith, CS Fox, JG AF Franklin, CL Gorelick, PL Riley, LK Dewhirst, FE Livingston, RS Ward, JM Beckwith, CS Fox, JG TI Helicobacter typhlonius sp nov., a novel murine urease-negative Helicobacter species SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; CHRONIC ACTIVE HEPATITIS; SCID MICE; SYRIAN-HAMSTERS; CAMPYLOBACTER-CINAEDI; BACTERIAL-INFECTION; LABORATORY MICE; BILIS; IDENTIFICATION; GASTRITIS AB Over the past decade, several Helicobacter species have been isolated from rodents. With the advent of PCR for the diagnosis of infectious agents, it has become clear that several previously uncharacterized Helicobacter species also colonize rodents. In this report, we describe a novel urease-negative helicobacter, Helicobacter typhlonius sp. nov., which was isolated from colonies of laboratory mice independently by two laboratories. Infection of immunodeficient mice by this bacterium resulted in typhlocolitis similar to that observed with other helicobacter infections. H. typhlonius is genetically most closely related to H. hepaticus. Like H. hepaticus, it is a spiral bacterium with bipolar sheathed flagella. However, this novel species contains a large intervening sequence in its 16S rRNA gene and is biochemically distinct from H. hepaticus. Notably, H. typhlonius does not produce urease or H2S nor does it hydrolize indoxyl-acetate. Compared to other Helicobacter species that commonly colonize rodents, H. typhlonius was found to be less prevalent than H. hepaticus and H. rodentium but as prevalent as H. bilis. H. typhlonius joins a growing list of helicobacters that colonize mice and are capable of inducing enteric disease in various strains of immunodeficient mice. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Univ Missouri, Dept Vet Pathobiol, Res Anim Diagnost & Investigat Lab, Columbia, MO 65211 USA. NCI, Anim Hlth Diagnost Lab, Lab Anim Sci Program, FCRDC,Sci Applicat Int Corp, Frederick, MD 21701 USA. Forsyth Inst, Boston, MA 02115 USA. Natl Canc Inst, Vet & Tumor Pathol Sect, Ctr Canc Res, Boston, MA 02115 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, Bldg 16-825C,77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NCI NIH HHS [R01 CA067529, R01CA67529]; NCRR NIH HHS [P41RR0600] NR 48 TC 40 Z9 41 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2001 VL 39 IS 11 BP 3920 EP 3926 DI 10.1128/JCM.39.11.3920-3926.2001 PG 7 WC Microbiology SC Microbiology GA 488KK UT WOS:000171934200017 PM 11682508 ER PT J AU Mayer, RJ AF Mayer, RJ TI Oral versus intravenous fluoropyrimidines for advanced colorectal cancer: By either route, it's all the same SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID 5-FLUOROURACIL C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 16 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2001 VL 19 IS 21 BP 4093 EP 4096 PG 4 WC Oncology SC Oncology GA 487WB UT WOS:000171901100001 PM 11689576 ER PT J AU Colleoni, M Gelber, S Coates, AS Castiglione-Gertsch, M Gelber, RD Price, K Rudenstam, CM Lindtner, J Collins, J Thurlimann, B Holmberg, SB Cortes-Funes, H Simoncini, E Murray, E Fey, M Goldhirsch, A AF Colleoni, M Gelber, S Coates, AS Castiglione-Gertsch, M Gelber, RD Price, K Rudenstam, CM Lindtner, J Collins, J Thurlimann, B Holmberg, SB Cortes-Funes, H Simoncini, E Murray, E Fey, M Goldhirsch, A CA Int Breast Canc Study Grp TI Influence of endocrine-related factors on response to perioperative chemotherapy for patients with node-negative breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LIGAND-BINDING ASSAY; ESTROGEN-RECEPTOR; ADJUVANT CHEMOTHERAPY; C-ERBB-2 EXPRESSION; ANGIOGENIC ACTIVITY; TUMOR-GROWTH; CELL-LINES; THERAPY; STIMULATION; REMOVAL AB Purpose: We investigated tumor- and patient-related features that might influence the response to perioperative chemotherapy (PeCT) compared with no adjuvant therapy for patients with node-negative breast cancer. Patients and Methods: A total of 1,275 patients were randomized to either no adjuvant treatment (427 patients) or PeCT (848 patients). The following variables thought to have prognostic significance were evaluated: grade, tumor size, estrogen (ER) and progesterone receptor (PgR) content (absent; low, 1 to 9 fmol/mg cytosol protein; or positive, greater than or equal to 10 fmol/mg cytosol protein), c-erbB-2 overexpression, menopausal status, and age. Cox proportional hazards regression models were used to assess the relative influence of these factors to predict the effect of PeCT on disease-free survival (DFS). Median follow-up was 13.5 years. Results: The 10-year DFS percentage for 692 premenopausal patients did not significantly differ be-tween the PeCT and no-adjuvant-treatment groups: 61% and 59%, respectively (relative risk [RR], 0.95; 95% confidence interval [Cl], 0.75 to 1.20; P = .70). No predictive factors were identified. For 583 postmenopausal patients, 10-year DFS percentages for the groups were 63% and 58%, respectively (RR, 0.75; 95% Cl, 0.58 to 0.93; P = .03). The absence of expression of ER, PgR, or both ER and PgR was the most important factor predicting improved outcome with PeCT among postmenopausal patients. The 10-year DFS percentages were 85% and 53% for the steroid hormone receptor-absent cohort of treated and untreated patients, respectively (RR, 0.18; 95% Cl, 0.06 to 0.49; P = .0009). Conclusion: The role of PeCT should be explored for patients whose primary tumors do not express steroid hormone receptors, because it is likely that early initiation of treatment is exclusively relevant for such patients. J Clin Oncol 79.4747-4149. (C) 2001 by American Society of Clinical Oncology. C1 Ist Europeo Oncol, Div Med Oncol, I-20141 Milan, Italy. Spedali Civil Brescia, Fondaz Beretta, I-25125 Brescia, Italy. Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Australian Can Soc, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Univ Melbourne, Anticanc Council Victoria, Melbourne, Vic, Australia. Univ Bern, Inselspital, Inst Med Oncol, CH-3010 Bern, Switzerland. Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. Kantonsspital, St Gallen, Switzerland. Osped Civ, Inst So Switzerland, Lugano, Switzerland. Sahlgrens Univ Hosp, Western Swedish Breast Canc Study Grp, S-41345 Gothenburg, Sweden. Inst Oncol, Ljubljana, Slovenia. Hosp Seguridad Social, Madrid, Spain. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. RP Colleoni, M (reprint author), Ist Europeo Oncol, Div Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. FU NCI NIH HHS [CA-75362] NR 38 TC 57 Z9 59 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2001 VL 19 IS 21 BP 4141 EP 4149 PG 9 WC Oncology SC Oncology GA 487WB UT WOS:000171901100007 PM 11689582 ER PT J AU Rosling, B Hellstrom, MK Ramberg, R Socransky, SS Lindhe, J AF Rosling, B Hellstrom, MK Ramberg, R Socransky, SS Lindhe, J TI The use of PVP-iodine as an adjunct to non-surgical treatment of chronic periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE maintenance; non-surgical therapy; periodontitis; ultrasonic device ID STAGE FULL-MOUTH; EARLY-ONSET PERIODONTITIS; POVIDONE-IODINE; CHRONIC ADULT; DISINFECTION; DISEASE; GINGIVITIS; MANAGEMENT; THERAPY; PLAQUE AB Objective: The present study was performed to assess the effect of topically-applied PVP-iodine, used as an adjunct both during basic non-surgical therapy and at re-treatment during the long-term maintenance of patients with advanced periodontal disease. Material and Methods: 223 patients with advanced destructive periodontitis were recruited. The participants met the following inclusion criteria: (i) a minimum of 8 non-molar teeth, (ii) probing pocket depth of greater than or equal to6 mm at greater than or equal to2 teeth in each dentate quadrant, and radiographic bone loss exceeding 40% at the same teeth, A baseline I examination included assessment of plaque, gingivitis, probing pocket depth (PPD), probing attachment level (PAL) and radiographic bone height (RXBL). Following baseline I, the patients were stratified into 2 treatment groups; 2 subjects out of 3 were included in a control group and I in a test group. All participants, on an individual basis, received a case presentation and were instructed in proper self-performed plaque control measures. Non-surgical therapy was performed by the use of an ultrasonic device. The instrumentation in the test group was combined with the administration of 0.1% PVP-iodine. All subjects were recalled for comprehensive examinations 3, 6 and 12 months (baseline 11) after baseline I and then after 3, 5 and 13 years of maintenance therapy. PAL determinations were performed annually. Subjects (losers) who at the re-examinations after 1, 2 and 3 years of maintenance demonstrated an annual further loss of PAL greater than or equal to2 mm at greater than or equal to4 teeth were exited from the study and referred for retreatment. There were 9 losers in the test and 31 in the control group. In addition, 8 subjects in the test and 25 subjects in the control group withdrew from the trial for reasons unrelated to the study. These 73 subjects were not included in the data presentation from the various examinations. Results: It was demonstrated that non-surgical periodontal therapy resulted in (i) improved gingival conditions, (ii) reduced PPD, (iii) gain in PAL. It was also documented that the topical application of 0.1% PVP-iodine in conjunction with the mechanical root debridement established conditions which further improved the outcome of therapy. This was evidenced by the fact that at the 3, 6, and 12 months re-examinations after baseline 1, the test group had significantly lower mean PPD values and significantly more gain of PAL than the control group. During the 12 years of SPT, it was possible for most subjects in both groups to maintain shallow pockets and to avoid marked further loss of PAL. There were, however, a larger number of losers in the control than in the test group. Conclusion: PVP-iodine, topically applied during subgingival instrumentation, may improve the outcome of non-surgical periodontal therapy. C1 Gothenburg Univ, Fac Odontol, Dept Periodontol, SE-40530 Gothenburg, Sweden. Forsyth Inst, Boston, MA USA. RP Rosling, B (reprint author), Gothenburg Univ, Fac Odontol, Dept Periodontol, Box 450, SE-40530 Gothenburg, Sweden. FU NIDCR NIH HHS [DE-12861] NR 30 TC 37 Z9 39 U1 0 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD NOV PY 2001 VL 28 IS 11 BP 1023 EP 1031 DI 10.1034/j.1600-051X.2001.281106.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 487AD UT WOS:000171850800006 PM 11686823 ER PT J AU Payne, TL Skobe, Z Yelick, PC AF Payne, TL Skobe, Z Yelick, PC TI Regulation of tooth development by the novel type I TGF beta family member receptor Alk8 SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE tooth specification and development; bone morphogenetic protein (Bmp) family member signaling; activin-like-kinase (Alk) receptors; bone morphogenetic proteins (BMPs); epithelial-mesenchymal cell interactions ID BRANCHIAL ARCH MUTANTS; DANIO-RERIO TELEOSTEI; MOUSE EMBRYOGENESIS; ZEBRAFISH; CYPRINIDAE; MORPHOGENESIS; ACTIVIN; DIFFERENTIATION; GASTRULATION; REPLACEMENT AB We have recently identified, in zebrafish, a novel type I receptor of the TGFbeta family, alk8, that participates in Bmp signaling pathways to mediate early dorsoventral patterning of neurectodermal and mesendodermal tissues. Since Bmps play significant roles in tooth specification, initiation, and differentiation, we hypothesized that alk-8 may play a role in directing the Bmp-mediated epithelial mesenchymal cell interactions regulating tooth development. Immunohistochemical analysis demonstrates that Alk-8 is expressed in developing zebrafish and mouse teeth. Examination of tooth development in zebrafish with disrupted alk8 signaling revealed specific defects in tooth development. Ectopic expression of constitutively active Alk8 results in the formation of elongated tooth structures, while expression of dominant-negative Alk8 results in arrested tooth development at the bud stage. These results are consistent with the established requirements for Bmp signaling in tooth development and demonstrate that Alk8 is a key regulator of tooth development. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Forsyth Dept Oral Biol, Boston, MA 02115 USA. Dept Biomineralizat, Boston, MA 02115 USA. RP Yelick, PC (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 The Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE05736, DE12024, DE12076] NR 29 TC 16 Z9 16 U1 1 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2001 VL 80 IS 11 BP 1968 EP 1973 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 536DB UT WOS:000174684500004 PM 11759004 ER PT J AU Chuang, SK Tian, L Wei, LJ Dodson, TB AF Chuang, SK Tian, L Wei, LJ Dodson, TB TI Kaplan-Meier analysis of dental implant survival: A strategy for estimating survival with clustered observations SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE dental implant; survival analysis; Kaplan-Meier Estimator; consistency; asymptotic variance; dependency; correlation ID PARTIALLY EDENTULOUS JAWS; PROSPECTIVE MULTICENTER; ITI-IMPLANTS; LIFE TABLE AB The study's purposes were to estimate dental implant survival in a statistically valid mariner and to compare three models for estimating survival. We estimated survival using three different statistical models: (1) randomly selecting one implant per patient; (2) utilizing all implants, assuming independence among implants from the same subject; and (3) utilizing all implants, assuming dependence among implants from the same subject. The cohort was composed of 660 patients who had 2286 implants placed. Due to the high success rates of implants, the five-year survival point and standard error estimates varied little among the three models. Patients at high risk for implant failure (smokers) manifested greater variation in the standard error estimates among the three models, 8.2%, 4.0%, and 5.6%, respectively. To obtain statistically valid survival confidence intervals when per-forming Kaplan-Meier survival analyses, we recommend adjusting for dependence when there are multiple observations within the same subject. C1 Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP POB 67376,Chestnut Hill Stn, Chestnut Hill, MA 02467 USA. EM schuang@hsph.harvard.edu FU NCI NIH HHS [R01 CA56844]; NIDCR NIH HHS [K16 DE00275, K24 DE00448] NR 25 TC 81 Z9 82 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2001 VL 80 IS 11 BP 2016 EP 2020 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 536DB UT WOS:000174684500013 PM 11759013 ER PT J AU Lucenti, MJ Nadel, ES Brown, DFM AF Lucenti, MJ Nadel, ES Brown, DFM TI Right lower quadrant pain SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID COMPUTED-TOMOGRAPHY; ACUTE APPENDICITIS; DIAGNOSIS C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Cambridge, MA 02138 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2001 VL 21 IS 4 BP 431 EP 434 DI 10.1016/S0736-4679(01)00420-6 PG 4 WC Emergency Medicine SC Emergency Medicine GA 497BE UT WOS:000172432200015 PM 11728774 ER PT J AU Gerber, A Masquelet, AC AF Gerber, A Masquelet, AC TI Anatomy and intracompartmental pressure measurement technique of the pronator quadratus compartment SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE compartment syndrome; pronator quadratus; pressure measurement AB The compartment of the pronator quadratus muscle in 25 cadaver specimens is described. Defined by the radius, ulna, and distal interosseous membrane dorsally and the pronator quadratus fascia on the palmar side, the osteofibrous walls of the compartment confine the pronator quadratus muscle within a noncompliant space. A safe and reliable location for compartment pressure measurement was defined at a site 4 cm proximal to the scaphoid tubercule, on the radial side of the flexor carpi radialis tendon and on the ulnar side of the radial artery. These clear anatomic definitions might be useful in diagnosis of compartment syndrome of the pronator quadratus; a clinical investigation may be justified on the basis of pressure measurements made using this technique. Copyright (C) 2001 by the American Society for Surgery of the Hand. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02114 USA. Univ Paris 13, Dept Orthoped Surg & Traumatol, Hop Avicenne, Bobigny, France. RP Gerber, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, 275 Cambridge St,POB 403, Boston, MA 02114 USA. RI Gerber Popp, Ariane/O-2781-2014 OI Gerber Popp, Ariane/0000-0002-6798-3676 NR 11 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 2001 VL 26A IS 6 BP 1129 EP 1134 DI 10.1053/jhsu.2001.26656 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 496TJ UT WOS:000172412500023 PM 11721264 ER PT J AU Grunenfelder, J Akins, CW Hilgenberg, AD Vlahakes, GJ Torchiana, DF Madsen, FC MacGillivray, TE AF Grunenfelder, J Akins, CW Hilgenberg, AD Vlahakes, GJ Torchiana, DF Madsen, FC MacGillivray, TE TI Long-term results and determinants of mortality after surgery for native and prosthetic valve endocarditis SO JOURNAL OF HEART VALVE DISEASE LA English DT Article; Proceedings Paper CT 1st Biennial Meeting of the Society-for-Heart-Valve-Disease CY JUN 15-18, 2001 CL LONDON, ENGLAND SP Soc Heart Valve Dis ID ACTIVE INFECTIVE ENDOCARDITIS; SURGICAL-TREATMENT; BACTERIAL-ENDOCARDITIS; NECROPSY PATIENTS; REPLACEMENT; BIOPROSTHESES; EXPERIENCE; REPAIR AB Background and aim of the study: The study aim was to describe the long-term results and determinants of mortality after operative treatment of native and prosthetic valve endocarditis at a single institution. Methods: Between March 1985 and October 1999,171 patients underwent surgery for native (NVE) or prosthetic valve endocarditis (PVE). NVE was present in 98 patients (57%), and PVE in 73 patients (43%). Mean follow up was 5.6 +/- 3.9 years (range: 0 to 15 years). Results: Overall hospital mortality was 9.9% (n = 17). Hospital mortality was higher among patients with PVE (15.1%) than those with NVE (6.1%; p = 0.05). Overall survival at 10 years was 46 +/- 5%. Patients with NVE had a higher 10-year survival rate (53 +/- 7%) than those with PVE (37 +/- 7%; p = 0.02). At 10 years, overall freedom from any late complication was 47 +/- 6% and from residual or recurrent endocarditis was 78 +/- 5%. Predictors of hospital death were emergency surgery (p <0.003) and preoperative renal insufficiency (p <0.008). Predictors of late death were age > 70 years (p <0.002), renal failure (p <0.03) and fungal endocarditis (p <0.04). Conclusion: These findings demonstrate the increased perioperative, as well as postoperative, risks associated with PVE versus NVE. Cardiac and extracardiac manifestations of the disease, as well as fungal organisms, but not the activity of the endocarditis, were significant adverse determinants of late outcome. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. Univ Zurich Hosp, Clin Cardiovasc Surg, Zurich, Switzerland. RP Akins, CW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Surg Unit, 55 Fruit St, Boston, MA 02114 USA. NR 27 TC 22 Z9 22 U1 0 U2 0 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD, ENGLAND HA6 2ET SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD NOV PY 2001 VL 10 IS 6 BP 694 EP 700 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 496YZ UT WOS:000172427100001 PM 11767173 ER PT J AU Parhami-Seren, B Viswanathan, M Strong, RK Margolies, MN AF Parhami-Seren, B Viswanathan, M Strong, RK Margolies, MN TI Structural analysis of mutants of high-affinity and low-affinity p-azophenylarsonate-specific antibodies generated by alanine scanning of heavy chain complementarity-determining region 2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; ARS-A ANTIBODIES; IMMUNE-RESPONSE; VARIABLE REGION; 3-DIMENSIONAL STRUCTURE; JUNCTIONAL DIVERSITY; SOMATIC MUTATIONS; GERMINAL-CENTERS; B-CELLS; EXPRESSION AB Alanine scanning was used to determine the affinity contributions of 10 side chain amino acids (residues at position 50-60 inclusive) of H chain complementarity-determining region 2 (HCDR2) of the somatically mutated high-affinity anti-p-azophenylarsonate Ab, 36-71. Each mutated H chain gene was expressed in the context of mutated (36-71L) and the unmutated (36-65L) L chains to also assess the contribution of L chain mutations to affinity. Combined data from fluorescence quenching, direct binding, inhibition, and capture assays indicated that mutating H:Tyr(50) and H:Tyr(57) to Ala in the 36-71 H chain results in significant loss of binding with both mutated (36-71L) or unmutated (36-65L) L chain, although the decrease was more pronounced when unmutated L chain was used. All other HCDR2 mutations in 36-71 had minimal effect on Ab affinity when expressed with 36-71 L chain. However, in the context of unmutated L chain, of H:Gly(54) to Ala resulted in significant loss of binding, while Abs containing Asn(52) to Ala, Pro(53) to Ala, or Ile(58) to Ala mutation exhibited 4.3- to 7.1-fold reduced affinities. When alanine scanning was performed instead on certain HCDR2 residues of the germline-encoded (unmutated) 36-65 Ab and expressed with unmutated L chain as Fab in bacteria, these mutants exhibited affinities similar to or slightly higher than the wild-type 36-65. These findings indicate an important role of certain HCDR2 side chain residues on Ab affinity and the constraints imposed by L chain mutations in maintaining Ag binding. C1 Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. Massachusetts Gen Hosp, Dept Surg, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Parhami-Seren, B (reprint author), Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. FU NCI NIH HHS [CA24432]; NHLBI NIH HHS [HL52282, HL47415]; NIAID NIH HHS [AI33175] NR 38 TC 2 Z9 3 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2001 VL 167 IS 9 BP 5129 EP 5135 PG 7 WC Immunology SC Immunology GA 487DN UT WOS:000171858500045 PM 11673524 ER PT J AU Bergwitz, C Prochnau, A Mayr, B Kramer, FJ Rittierodt, M Berten, HL Hausamen, JE Brabant, G AF Bergwitz, C Prochnau, A Mayr, B Kramer, FJ Rittierodt, M Berten, HL Hausamen, JE Brabant, G TI Identification of novel CBFA1/RUNX2 mutations causing cleidocranial dysplasia SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID OSTEOBLAST DIFFERENTIATION; BONE-DEVELOPMENT; CBFA1; GENE; MICE; OSF2/CBFA1; CHILDREN; BINDING; GROWTH; LOCUS AB Core binding factor A1 (CBFA1/RUNX2) is a runt-like transcription factor essential for osteoblast differentiation. Haplotype insufficiency causes cleidocranial dysplasia (CCD), a syndrome featuring supernumerary tooth buds, delayed tooth eruption, patent fontanels, Wormian bones, short stature, dysplasia of the clavicles, growth retardation and hypoplasia of the distal phalanges. We identified novel CBFA1/RUNX2 mutations after PCR and direct sequencing of patient leukocyte DNA. In family 1 mother and son are affected by CCD. Both carry the missense mutation R190W (CGG > TGG). This nucleotide change introduced a BsmI restriction site, which was used to independently confirm the mutation. It was absent in healthy members of the family. Family 2, in which father and daughter are affected by CCD, shows a deletion of nucleotide C821. This deletion causes a frameshift mutation with premature stop after the insertion of 18 aberrant amino acids. Healthy family members did not have this mutation. The clavicular dysplasia was more pronounced with the R190W mutation, while the bone density was markedly reduced in individuals with either mutation, suggesting a previously underemphasized increased risk for osteoporosis in CCD. C1 Hannover Med Sch, Abt Klin Endokrinol, Hannover, Germany. Hannover Med Sch, Neurochirurg Klin, Hannover, Germany. Hannover Med Sch, Klin & Poliklin Mund Kiefer & Gesichtschirurg, Hannover, Germany. Hannover Med Sch, Klin Kieferorthopadie, Hannover, Germany. RP Bergwitz, C (reprint author), Massachusetts Gen Hosp, Dept Med, Blossom St, Boston, MA 02114 USA. RI Mayr, Bernhard/F-6936-2012 OI Mayr, Bernhard/0000-0002-8973-4494 NR 28 TC 21 Z9 25 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD NOV PY 2001 VL 24 IS 6 BP 648 EP 656 DI 10.1023/A:1012758925617 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 492KV UT WOS:000172168300004 PM 11768584 ER PT J AU Lange-Asschenfeldt, B Velasco, P Streit, M Hawighorst, T Pike, SE Tosato, G Detmar, M AF Lange-Asschenfeldt, B Velasco, P Streit, M Hawighorst, T Pike, SE Tosato, G Detmar, M TI The angiogenesis inhibitor vasostatin does not impair wound healing at tumor-inhibiting doses SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE calreticulin; cancer; endothelium; tissue repair ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-VESSEL MATURATION; ENDOGENOUS INHIBITOR; VASCULAR DEVELOPMENT; FACTOR EXPRESSION; TRANSGENIC MICE; SKIN; CALRETICULIN; ENDOSTATIN; THROMBOSPONDIN-2 AB Inhibition of tumor angiogenesis represents a promising new approach for the treatment of human cancers. It has remained unclear, however, whether inhibition of tumor angiogenesis may also result in impaired wound healing, a process thought to be angiogenesis dependent. To determine the effects of the angiogenesis inhibitor vasostatin, a 180 amino acid calreticulin fragment, on wound healing at tumor inhibiting doses, full-thickness wounds were generated on the back of nude mice that were also injected intradermally with CA46 Burkitt lymphoma cells. Mice were treated with daily injections of vasostatin or vehicle control at a site between the wounds and the transplanted tumor cells over 14 d. Vasostatin potently inhibited tumor growth and significantly reduced tumor angiogenesis, as measured by computer-assisted image analysis of CD31-stained tumor sections. Moreover, vasostatin treatment resulted in an increased fraction of mature tumor-associated blood vessels. In contrast, no impairment of wound healing was observed in vasostatin-treated mice, despite a significantly reduced vascularity of the wound granulation tissue. Our results reveal a different sensitivity of malignant tumor growth and physiologic wound healing to inhibition of angiogenesis, and they suggest that therapeutic inhibition of tumor angiogenesis may be achieved without impairment of tissue repair. C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Bldg 149,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [CA69184, CA86410] NR 38 TC 31 Z9 34 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 NOV PY 2001 VL 117 IS 5 BP 1036 EP 1041 DI 10.1046/j.0022-202x.2001.01519.x PG 6 WC Dermatology SC Dermatology GA 492ZX UT WOS:000172198500002 PM 11710910 ER PT J AU Rajadhyaksha, M Menaker, G Flotte, T Dwyer, PJ Gonzalez, S AF Rajadhyaksha, M Menaker, G Flotte, T Dwyer, PJ Gonzalez, S TI Confocal examination of nonmelanoma cancers in thick skin excisions to potentially guide mohs micrographic surgery without frozen histopathology SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE dermatology; lasers; optical imaging; optical microscopy; scanning; surgical pathology ID SCANNING LASER MICROSCOPY; IN-VIVO; POLARIZATION; SCATTERING; TISSUE; LIGHT AB Precise removal of nonmelanoma cancers with minimum damage to the surrounding normal skin is guided by the histopathologic examination of each excision during Mohs micrographic surgery. The preparation of frozen histopathology sections typically requires 20-45 min per excision. Real-time confocal reflectance microscopy offers an imaging method potentially to avoid frozen histopathology and prepare noninvasive (optical) sections within 5 min. Skin excisions (approximate to 1 mm thick) from Mohs surgeries were washed with 5% acetic acid and imaged with a confocal cross-polarized microscope. The confocal images were compared with the corresponding histopathology. Acetic acid causes compaction of chromatin that increases light back-scatter and makes the nuclei bright and easily detectable. Crossed-polarization strongly enhances the contrast of the nuclei because the compacted chromatin depolarizes the illumination light whereas the surrounding cytoplasm and normal dermis does not. Fast low-resolution examination of cancer lobules in wide fields of view followed by high-resolution inspection of nuclear morphology in small fields of view is possible; this is similar to the procedure for examining histopathology sections. Both the Mohs surgeon and the patient will potentially save several hours per day in the operating room. Fast confocal reflectance microscopic examination of excisions (of any thickness) may improve the management of surgical pathology and guide microsurgery of any human tissue. C1 Lucid Inc, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Dermatol Serv, Boston, MA 02114 USA. RP Rajadhyaksha, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Dermatol Serv, Barlett Extens 630, Boston, MA 02114 USA. NR 27 TC 106 Z9 107 U1 1 U2 2 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 NOV PY 2001 VL 117 IS 5 BP 1137 EP 1143 DI 10.1046/j.0022-202x.2001.01524.x PG 7 WC Dermatology SC Dermatology GA 492ZX UT WOS:000172198500016 PM 11710924 ER PT J AU Bayon, JE Pascolo, L Gonzalo-Orden, JM Altonaga, JR Gonzalez-Gallego, J Webster, C Haigh, WG Stelzner, M Pekow, C Tiribelli, C Ostrow, JD AF Bayon, JE Pascolo, L Gonzalo-Orden, JM Altonaga, JR Gonzalez-Gallego, J Webster, C Haigh, WG Stelzner, M Pekow, C Tiribelli, C Ostrow, JD TI Pitfalls in preparation of H-3-unconjugated bilirubin by biosynthetic labeling from precursor H-3-5-aminolevulinic acid in the dog SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID 5-AMINOLEVULINIC ACID; AMINOLEVULINIC-ACID; AQUEOUS-SOLUTION; UNCONJUGATED BILIRUBIN; NATIVE BILE; RAT; ANESTHESIA; MODEL; ISOFLURANE; METABOLISM AB We report problems encountered during preparation of tritium-labeled unconjugated bilirubin (H-3-UCB) from precursor H-3-5-aminolevulinic acid (H-3-ALA) in 2 dogs with external biliary drainage installed into the animals under general anesthesia. Under prolonged sedation, 12.9 or 14.0 mCi of H-3-ALA was administered intravenously in two divided doses, and bile was collected for 9 hours. In one animal, taurocholate (TC) infusion was needed to maintain bile flow. H-3-UCB was isolated from the bile and recrystallized with the improved method of Webster et al (Webster CC, Tiribelii! C, Ostrow JD. J Lab Clin Med 2001; 137:370-3). Based on radioactivity and pigment content, hourly bile collections were pooled to optimize specific activities. Surprisingly, in the first dog, only 2.9% of injected radioactivity was recovered in bile and only 14.1% in urine, and the specific activities of the crystalline H-3-UCB from the two pools were only 39.5 and 30.0 x 10(3) dpm/mug. High-performance liquid chromatography analysis revealed that only 4% of ALA degraded during 5 minutes in injection solution at pH 6.8. The low incorporation of H-3-ALA and low specific activity of H-3-UCB was apparently caused mainly by prior degradation and exchange of labile tritium of the H-3-ALA and probably by enhanced endogenous ALA synthesis caused by the anesthetic/sedative agents. Revised procedures in the second dog improved the incorporation of H-3-ALA to 11.9% excreted in bile and the specific activity of the crystalline H-3-UCB to 122.0 and 50.8 x 10(3) dpm/mug, while urinary excretion of tritium increased to 28.5%. These experiences emphasize possible pitfalls in preparing H-3-UCB by biosynthetic labeling from H-3-ALA administered to dogs. C1 Univ Leon, Dept Physiol, E-24071 Leon, Spain. Univ Leon, Dept Anim Pathol, E-24071 Leon, Spain. Univ Trieste, Dept Biochem Biophys & Chem Macromol, Trieste, Italy. Dept Vet Affairs Lakeside Med Ctr, Res Serv, Chicago, IL USA. Northwestern Univ, Div Gastroenterol Hepatol, Chicago, IL 60611 USA. Vet Affairs Puget Sound Hlth Care Syst, Res Serv, Gastroenterol Hepatol Lab, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Vet Med Unit, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Comparat Med, Seattle, WA USA. Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol Hepatol, NL-1105 AZ Amsterdam, Netherlands. RP Gonzalez-Gallego, J (reprint author), Univ Leon, Dept Physiol, E-24071 Leon, Spain. RI Gonzalez-Gallego, Javier/D-8219-2012; OI Gonzalez-Gallego, Javier/0000-0002-4386-9342 NR 36 TC 11 Z9 11 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD NOV PY 2001 VL 138 IS 5 BP 313 EP 321 DI 10.1067/mlc.2001.118746 PG 9 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 494KE UT WOS:000172280700003 PM 11709655 ER PT J AU Boedeker, JC Doolittle, MH White, AL AF Boedeker, JC Doolittle, MH White, AL TI Differential effect of combined lipase deficiency (cld/cld) on human hepatic lipase and lipoprotein lipase secretion SO JOURNAL OF LIPID RESEARCH LA English DT Article DE calnexin; castanospermine; endoplasmic reticulum; fetal hepatocytes; glucosidase enzymes ID ENDOPLASMIC-RETICULUM; BROWN ADIPOCYTES; MOUSE; MICE; EXPRESSION; METABOLISM; CALNEXIN; PLASMA; GENE; CLD AB Combined lipase deficiency (cld) is a recessively inherited disorder in mice associated with a deficiency of LPL and hepatic lipase (HL) activity. LPL is synthesized in cld tissues but is retained in the endoplasmic reticulum (ER), whereas mouse HL (mHL) is secreted but inactive. In this study we investigated the effect of cld on the secretion of human HL (hHL) protein mass and activity. Differentiated liver cell lines were derived from cld mice and their normal heterozygous (het) littermates by transformation of hepatocytes with SV40 large T antigen. After transient transfection with lipase expression constructs, secretion of hLPL activity from cld cells was only 12% of that from het cells. In contrast, the rate of secretion of hHL activity and protein mass per unit of expressed hHL mRNA was identical for the two cell lines. An intermediate effect was observed for mHL, with a 46% reduction in secretion of activity from cld cells. The ER glucosidase inhibitor, castanospermine, decreased secretion of both hLPL and hHL from het cells by similar to 70%, but by only similar to 45% from cld cells. This is consistent with data suggesting that cld may result from a reduced concentration of the ER chaperone calnexin. In conclusion, our results demonstrate a differential effect of cld on hLPL, mHL, and hHL secretion, suggesting differential requirements for activation and exit of the enzymes from the ER. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75390 USA. W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. RP White, AL (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. NR 28 TC 10 Z9 11 U1 0 U2 0 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 NOV PY 2001 VL 42 IS 11 BP 1858 EP 1864 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 498NQ UT WOS:000172517900015 PM 11714855 ER PT J AU Chen, YCI Mandeville, JB Nguyen, TV Talele, A Cavagna, F Jenkins, BG AF Chen, YCI Mandeville, JB Nguyen, TV Talele, A Cavagna, F Jenkins, BG TI Improved mapping of (pharmacologically induced neuronal activation using the IRON technique with superparamagnetic blood pool agents SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE CBV; CFT; BOLD; IRON; superparamagnetic; pharmacological MRI ID RAT FOREPAW STIMULATION; HUMAN BRAIN ACTIVITY; MAGNETIC-SUSCEPTIBILITY; PHARMACOLOGICAL MRI; SENSORY STIMULATION; FUNCTIONAL MRI; SIGNAL CHANGES; CONTRAST; OXIDE; FMRI AB The use of functional magnetic resonance imaging (fMRI) techniques for evaluation of pharmacologic stimuli has great potential for understanding neurotransmitter dynamics for a number of brain disorders, such as drug abuse, schizophrenia, epilepsy, or neurodegeneration. Unfortunately, blood oxygenation level-dependent (BOLD) imaging at common fields strengths, such as 1.5 or 3 T, has very low sensitivity and contrast-to-noise ratios (CNRs). We demonstrate here the utility of using an intravascular superparamagnetic iron oxide contrast agent with a long plasma half-life for evaluation of hemodynamic changes related to dopaminergic stimuli using amphetamine or the cocaine analog 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT). We refer to this technique as increased relaxation with iron oxide nanoparticles (IRON). Results obtained here show that even at field strengths as high as 4.7 T, one can obtain increases in CNR by factors of 2-3 over BOLD imaging that lead to greater than an order of magnitude increase in statistical power with greatly increased sensitivity to hemodynamic changes in brain regions difficult to observe using BOLD imaging. Furthermore, use of the intravascular contrast agent allows for a meaningful physiologic parameter to be measured (relative cerebral blood volume (rCBV)), compared to conventional BOLD imaging. (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiobiochem, Charlestown, MA 02129 USA. RP Jenkins, BG (reprint author), Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiobiochem, Charlestown, MA 02129 USA. NR 38 TC 51 Z9 53 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2001 VL 14 IS 5 BP 517 EP 524 DI 10.1002/jmri.1215 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 537LD UT WOS:000174759200003 PM 11747003 ER PT J AU Rogers, MP Orav, J Black, PM AF Rogers, MP Orav, J Black, PM TI The use of a simple Likert scale to measure quality of life in brain tumor patients SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE brain; tumor; quality of life; Likert scale ID LONG-TERM SURVIVORS; LOW-GRADE GLIOMAS; OF-LIFE; RADIATION-THERAPY; MALIGNANT ASTROCYTOMAS; MOOD DISORDERS; CANCER; ADULT AB The use of a self-administered 10-Point Likert self-assessment quality of life scale was explored in a convenience sample of patients attending a brain tumor clinic. The original scale, developed by Priestman, was modified to be more brain-tumor specific. A total of 430 patients completed the scale at 535 different points of measurement. The patients had a variety of brain tumors ranging from meningiomas to high-grade gliomas. The Total Score of the original scale and the Modified Total Score of the brain-specific version were explored in relationship to patient demographics and available clinical characteristics: age, gender, severity of tumor, location of tumor, survival rates, prior surgery, radiation, radiosurgery, and chemotherapy. We also examined the relationship between sub-scales and these variables. On a scale of 10-100, the average Total Score was 67.83, not significantly different from the Modified Score. There were no differences between bilateral, midline, or left- versus right-sided lesions. Patients with the worst prognosis in terms of tumor type were 5-6 points lower in quality of life than patients with intermediate or relatively good prognosis. In a multiple regression model, adjusted for age, the overall score was related only to tumor severity and to gender, with women having significantly poorer functional status than men by 4 points. Both the Modified and Total Scores were significantly associated with higher mortality risk, and more specifically, poor scores on well-being, mood, physical function, house/job performance, self-care, concentration, and energy all predicted higher mortality risk. We suggest that the simplicity of this instrument may make it particularly useful for longitudinal assessment of quality of life in brain tumor patients. C1 Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Brigham & Womens Hosp, Brain Tumor Ctr, Dana Farber Canc Inst, Joint Ctr Radiat Therapy,Childrens Hosp Med Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Rogers, MP (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. NR 24 TC 19 Z9 20 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD NOV PY 2001 VL 55 IS 2 BP 121 EP 131 DI 10.1023/A:1013381816137 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 504MV UT WOS:000172861200007 PM 11817703 ER PT J AU Koedel, U Paul, R Winkler, F Kastenbauer, S Huang, PL Pfister, HW AF Koedel, U Paul, R Winkler, F Kastenbauer, S Huang, PL Pfister, HW TI Lack of endothelial nitric oxide synthase aggravates murine pneumococcal meningitis SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE CNS inflammation; endothelial nitric oxide synthase; meningitis; mouse model; nitric oxide; Streptococcus pneumoniae ID BLOOD-BRAIN-BARRIER; TUMOR-NECROSIS-FACTOR; BACTERIAL-MENINGITIS; OXIDATIVE STRESS; GENE-EXPRESSION; ENDOTOXIN-SHOCK; TISSUE-DAMAGE; MICE LACKING; IN-VIVO; RAT AB Nitric oxide (NO) plays a central role in the pathogenesis of bacterial meningitis. However, the role of NO produced by endothelial NO synthase (eNOS) in meningitis is still unclear. We investigated the influence of eNOS depletion on the inflammatory host response, intracranial complications, and outcome in experimental pneumococcal meningitis. Leukocyte accumulation in the cerebrospinal fluid was more, pronounced in infected eNOS-deficient mice than in infected wild type mice. This effect could be attributed to an increased expression of P-selectin, macrophage inflammatory protein-2, keratinocyte-derived cytokine, and interleukin (IL)-1 beta in the brain of infected eNOS-deficient mice. However, no differences in the cerebral expression of intercellular adhesion molecule-1, tumor necrosis factor-alpha, and IL-6 as well as of neuronal NOS and inducible NOS could be detected between infected wild type and mutant mice. In addition to enhanced leukocyte infiltration into the CSF, meningitis-associated intracranial complications including blood-brain barrier disruption and the rise in intracranial pressure were significantly augmented in infected eNOS-deficient mice. The aggravation of intracranial complications was paralleled by a worsening of the disease, as evidenced by a more pronounced hypothermia, an enhanced weight reduction, and an increased death rate. The current data indicate that eNOS deficiency is detrimental in bacterial meningitis. This effect seems to be related to an increased expression of (certain) cytokines/chemokines and adhesion molecules; thus leading to increased meningeal inflammation and, subsequently, to aggravated intracranial complications. C1 Univ Munich, Klinikum Grosshadern, Dept Neurol, D-81377 Munich, Germany. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pfister, HW (reprint author), Univ Munich, Klinikum Grosshadern, Dept Neurol, Marchioninistr 15, D-81377 Munich, Germany. NR 72 TC 44 Z9 46 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 2001 VL 60 IS 11 BP 1041 EP 1050 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 487FV UT WOS:000171863700003 PM 11706934 ER PT J AU Brown, MC AF Brown, MC TI Response adaptation of medial olivocochlear neurons is minimal SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID AUDITORY-NERVE FIBERS; ANTEROVENTRAL COCHLEAR NUCLEUS; SHORT-TERM ADAPTATION; GUINEA-PIG COCHLEA; ELECTRICAL-STIMULATION; REGULARITY ANALYSIS; EFFERENT NEURONS; HAIR CELLS; CAT; RECOVERY AB Response adaptation is a general characteristic of neurons. A number of studies have investigated the adaptation characteristics of auditory-nerve fibers, which send information to the brain about sound stimuli. However, there have been no previous adaptation studies of olivocochlear neurons, which provide efferent fibers to hair cells and auditory nerve dendrites in the auditory periphery. To study adaptation in efferent fibers, responses of single olivocochlear neurons were recorded to characteristic-frequency tones and noise, using anesthetized guinea pigs. To measure short-term adaptation, stimuli of 500 ms duration were presented, and the responses were displayed as peristimulus time histograms. These histograms showed regular peaks, indicating a "chopping" pattern of response. The rate during each chopping period as well as the general trend of the histogram could be well fit by an equation that expresses the firing rate as a sum of 1) a short-term adaptive rate that decays exponentially with time and 2) a constant steady-state rate. For the adaptation in medial olivocochlear (MOC) neurons, the average exponential time constant was 47 ms, which is roughly similar to that for short-term adaptation in auditory-nerve fibers. The amount of adaptation (expressed as a percentage decrease of onset firing rate), however, was substantially less in MOC neurons (average 31%) than in auditory-nerve fibers (average 63%). To test for adaptation over longer periods, we used noise and tones of 10 s duration. After the short-term adaptation, the responses of MOC neurons were almost completely sustained (average long-term adaptation 3%). However, in the same preparations, significant long-term adaptation was present in auditory-nerve fibers. These results indicate that the MOC response adaptation is minimal compared with that of auditory-nerve fibers. Such sustained responses may enable the MOC system to produce sustained effects in the periphery, supporting a role for this efferent system during ongoing stimuli of long duration. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard MIT Div Hlth Sci & Technol, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC-01089] NR 61 TC 8 Z9 8 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 NOV PY 2001 VL 86 IS 5 BP 2381 EP 2392 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 489VH UT WOS:000172012800024 PM 11698528 ER PT J AU Kinoshita, A Whelan, CM Smith, CJ Mikhailenko, I Rebeck, GW Strickland, DK Hyman, BT AF Kinoshita, A Whelan, CM Smith, CJ Mikhailenko, I Rebeck, GW Strickland, DK Hyman, BT TI Demonstration by fluorescence resonance energy transfer of two sites of interaction between the low-density lipoprotein receptor-related protein and the amyloid precursor protein: Role of the intracellular adapter protein Fe65 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amyloid precursor protein; APP; low-density lipoprotein; receptor-related protein; LRP; adaptor protein Fe65; fluorescent resonance energy transfer; FRET; protein-protein interaction; secretory pathway; immunocytochemistry; confocal microscopy ID ALPHA-2-MACROGLOBULIN RECEPTOR; ALZHEIMERS-DISEASE; NEUROFIBRILLARY TANGLES; DISTINCT SITES; SURFACE; ASSOCIATION; BINDING; DOMAIN; CELLS; COMPARTMENT AB Amyloid-beta, the major constituent of senile plaques in Alzheimer's disease, is derived from the amyloid precursor protein (APP) by proteolysis. Kunitz protease inhibitor (KPI) containing forms of APP (APP751/770) interact with a multifunctional endocytic receptor, the low-density lipoprotein receptor-related protein (LRP), which modulates its proteolytic processing affecting production of amyloid-beta. We used fluorescence resonance energy transfer (FRET) using labeled LRP and APP in H4 cell line to examine the subcellular localization and the molecular domains involved in the APP-LRP interaction. KPI-containing forms of APP (APP770) demonstrated FRET with LRP that was sensitive to the LRP inhibitor receptor-associated protein (RAP), suggesting an interaction between the extracellular domains of APP770 and LRP. APP695 also interacts with LRP to lesser degree (as measured by extracellular domain probes), and this ectodomain interaction is not altered by RAP. By using C-terminally tagged LRP and APP, we demonstrate a second site of interaction between the C termini of both APP695 and APP770 and the C terminus of LRP, and that the interactions at these regions are not sensitive to RAP. We next examined the possibility that the C-termini APP-LRP interaction was mediated by Fe65, an adaptor protein that interacts with the cytoplasmic tails of LRP and APP. FRET studies confirmed a close proximity between the amino Fe65 phosphotyrosine binding (PTB) domain and LRP cytoplasmic domain and between the carboxyl Fe65 PTB domain and the APP cytoplasmic domain. These findings demonstrate that LRP interaction with APP occurs via both extracellular and intracellular protein interaction domains. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Lab, Alzheimers Dis Res Unit, Charlestown, MA 02129 USA. Amer Red Cross, Holland Lab, Dept Vasc Biol, Rockville, MD 20855 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Lab, Alzheimers Dis Res Unit, 114 16th St,Room 2009, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL50784]; NIA NIH HHS [AG12406, AG14473] NR 31 TC 124 Z9 126 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2001 VL 21 IS 21 BP 8354 EP 8361 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 482ZL UT WOS:000171608600014 PM 11606623 ER PT J AU Lim, GP Chu, T Yang, FS Beech, W Frautschy, SA Cole, GM AF Lim, GP Chu, T Yang, FS Beech, W Frautschy, SA Cole, GM TI The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's disease; inflammation; oxidative damage; anti-oxidant; microglia; plaque; interleukin-1 beta; Tg2576; APPswedish ID APOLIPOPROTEIN-E; LIPID-PEROXIDATION; IN-VIVO; PRECURSOR PROTEIN; BETA-PROTEIN; ALPHA-TOCOPHEROL; FIBRIL FORMATION; OXYGEN RADICALS; FATTY-ACIDS; DISEASE AB Inflammation in Alzheimer's disease (AD) patients is characterized by increased cytokines and activated microglia. Epidemiological studies suggest reduced AD risk associates with long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed inflammation and plaque-related pathology in an Alzheimer transgenic APPSw mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I can cause gastrointestinal, liver, and renal toxicity. One alternative NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an extensive history as a food additive and herbal medicine in India and is also a potent polyphenolic antioxidant. To evaluate whether it could affect Alzheimer-like pathology in the APPSw mice, we tested a low (160 ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation, oxidative damage, and plaque pathology. Low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1 beta, a proinflammatory cytokine elevated in the brains of these mice. With low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP was reduced, and insoluble beta -amyloid (A beta), soluble A beta, and plaque burden were significantly decreased by 43-50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced. Microgliosis was also suppressed in neuronal layers but not adjacent to plaques. In view of its efficacy and apparent low toxicity, this Indian spice component shows promise for the prevention of Alzheimer's disease. C1 Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Ctr Geriatr Res Educ & Clin, Dept Med,San Fernando Valley Program, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. RP Cole, GM (reprint author), Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Ctr Geriatr Res Educ & Clin, Dept Med,San Fernando Valley Program, GRECC11E,16111 Plummer St, Sepulveda, CA 91343 USA. FU NIA NIH HHS [AG13471, R01 AG013741, U01 AG028583] NR 73 TC 816 Z9 861 U1 18 U2 132 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2001 VL 21 IS 21 BP 8370 EP 8377 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 482ZL UT WOS:000171608600016 PM 11606625 ER PT J AU Tolias, AS Smirnakis, SM Augath, MA Trinath, T Logothetis, NK AF Tolias, AS Smirnakis, SM Augath, MA Trinath, T Logothetis, NK TI Motion processing in the macaque: Revisited with functional magnetic resonance imaging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fMRI; motion; V1; MT; monkey; adaptation ID VISUAL AREA MT; DIRECTION SELECTIVITY; EXTRASTRIATE CORTEX; PERCEPTUAL DECISION; STRIATE CORTEX; MONKEY; NEURONS; CELLS; ADAPTATION; ORIENTATION AB A great deal is known about the response properties of single neurons processing sensory information. In contrast, less is understood about the collective characteristics of networks of neurons that may underlie sensory capacities of animals. We used functional magnetic resonance imaging to study the emergent properties of populations of neurons processing motion across different brain areas. Using a visual adaptation paradigm, we localized a distributed network of visual areas that process information about the direction of motion as expected from single-cell recording studies. However, we found an apparent discrepancy between the directional signals in certain visual areas as measured with blood oxygenation level-dependent imaging compared with an estimate based on the spiking of single neurons. We propose a hypothesis that may account for this difference based on the postulate that neuronal selectivity is a function of the state of adaptation. Consequently, neurons classically thought to lack information about certain attributes of the visual scene may nevertheless receive and process this information. We further hypothesize that this adaptation-dependent selectivity may arise from intra- or interarea cellular connections, such as feedback from higher areas. This network property may be a universal principle the computational goal of which is to enhance the ability of neurons in earlier visual areas to adapt to statistical regularities of the input and therefore increase their sensitivity to detect changes along these stimulus dimensions. C1 Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02114 USA. RP Tolias, AS (reprint author), Max Planck Inst Biol Cybernet, Spermannstr 38, D-72076 Tubingen, Germany. NR 46 TC 76 Z9 76 U1 2 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 2001 VL 21 IS 21 BP 8594 EP 8601 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 482ZL UT WOS:000171608600038 PM 11606647 ER PT J AU August, M Chung, K Chang, Y Glowacki, J AF August, M Chung, K Chang, Y Glowacki, J TI Influence of estrogen status on endosseous implant osseointegration SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgery CY SEP, 2000 CL SAN FRANSICAO, CALIFORNIA SP Amer Assoc Oral & Maxillofacial Surg ID POSTMENOPAUSAL WOMEN; MINERAL DENSITY; OSTEOPOROSIS; BONE; PHARMACOKINETICS; ABSORPTIOMETRY; ESTRADIOL; THERAPY; DISEASE AB Purpose: This retrospective study tested the hypothesis that postmenopausal women have lower rates of osseointegration of endosseous implants than premenopausal women and male controls. The role of estrogen replacement therapy (ERT) was also evaluated. Patients and Methods: Review of medical records allowed identification of patients who had received endosseous implants. Patients with concurrent illness, a smoking or ethanol use history, or metabolic bone disease were excluded. Five groups of subjects were identified: 1) 168 postmenopausal women without ERT; 2) 75 postmenopausal women supplemented with ERT; 3) 114 premenopausal women; 4) 59 men younger than 50 years; and 5) 110 men older than 50 years. Successful osseointegration was defined as stability at uncovering using a manual torque wrench and was confirmed radiographically. Failure rate comparisons were made between groups using both Fisher's exact tests and Poisson regression models. Results: Postmenopausal women without ERT had the highest maxillary failure rate (13.6%) which was significantly greater than for premenopausal women (6.3%, P = .039) and for men older than 50 (7.6%, P = .051). Although the maxillary failure rate of unsupplemented postmenopausal women was greater than for ERT supplemented women (8.1%), the comparison did not reach statistical significance (P = .17). The maxillary failure rate was similar between men younger than 50 years and those older than 50 years (6.3 vs 7.6%, not significant) Mandibular implant failures in all groups showed no statistically significant differences. Conclusion: The effect of postmenopausal estrogen status on compromised implant healing was shown in the maxilla but not in the mandible. Unsupplemented postmenopausal women had the highest failure rate. Although a statistical difference was not achieved, ERT reduced the maxillary failure rate by 41%. These results suggest that estrogen deficiency and the resultant bony changes associated with menopause may be risk factors for endosseous implant failure in the maxilla. (C) 2001 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Med Practices Evaluat Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. RP August, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. NR 29 TC 49 Z9 51 U1 0 U2 4 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 NOV PY 2001 VL 59 IS 11 BP 1285 EP 1289 DI 10.1053/joms.2001.27515 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 489YN UT WOS:000172020800008 PM 11688027 ER PT J AU Higuchi, LM Joffe, T Neufeld, EJ Weisdorf, S Rosh, J Murch, S Devenyi, A Thompson, JF Lewis, JD Bousvaros, A AF Higuchi, LM Joffe, T Neufeld, EJ Weisdorf, S Rosh, J Murch, S Devenyi, A Thompson, JF Lewis, JD Bousvaros, A TI Inflammatory bowel disease associated with immune thrombocytopenic purpura in children SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE inflammatory bowel disease; ulcerative colitis; Crohn's disease; thrombocytopenia; immune thrombocytopenic purpura ID ULCERATIVE-COLITIS; CROHNS-DISEASE; MANIFESTATIONS; NEUTROPENIA AB Objective: Previous reports suggest an association between inflammatory bowel disease (IBD) and immune thrombocytopenic purpura (ITP) in adults. To date, only five children with both diseases have been described. The aim of the study was to describe the characteristics of children with IBD and ITP. Methods: Cases were obtained from the pediatric gastroenterology community by means of the pediatric gastroenterology internet bulletin board in June 1999. Eight cases were submitted from seven medical centers. Medical records were reviewed by two pediatric gastroenterologists and a pediatric hematologist. Results: The age range of the patients was 2.1 to 16.5 years, with a mean age of 9.6 +/-5.2 years. Four children had ulcerative colitis, three had Crohn disease, and one had indeterminate colitis. All had colonic involvement of IBD. Of eight patients, three had IBD first, three had ITP first, and two had both simultaneously. At ITP diagnosis, platelet count was less than 10,000/mL in five children, 17,000/mL in one child, and 50,000 to 60,000/mL in two children. Of the three children diagnosed with ITP first, two initially had rectal bleeding at the time of ITP diagnosis. Bone marrow evaluations, performed in six of eight children, were consistent with ITP. Six of the eight children had chronic ITP, including three children who were 5 years of age or younger. Therapy for ITP included steroids (n=6), intravenous immunoglobulin (n=6), Rh (D) intravenous immunoglobulin (n=2), and splenectomy (n=1). Conclusions: The authors describe the largest pediatric case series of children with IBD and ITP. More than 50% of the children had the chronic form of ITP. Most patients responded to conventional therapy for ITP and IBD. C1 Childrens Hosp, Div Gastroenterol & Nutr, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Sch Med, Div Pediat Gastroenterol & Nutr, Minneapolis, MN 55455 USA. Atlantic Hlth Syst, Morristown, NJ USA. UCL Royal Free & Univ Coll Sch Med, Univ Dept Paediat Gastroenterol, London, England. Reg Gastroenterol Associates Lancaster Ltd, Lancaster, PA USA. Univ Miami, Sch Med, Div Pediat Gastroenterol & Nutr, Miami, FL USA. Childrens Ctr Digest Hlth Care, Atlanta, GA USA. RP Higuchi, LM (reprint author), Childrens Hosp, Div Gastroenterol & Nutr, Combined Program Pediat Gastroenterol & Nutr, Hunnewell Bldg,Ground Floor,300 Longwood Ave, Boston, MA 02115 USA. EM leslie.higuchi@tch.harvard.edu RI Neufeld, Ellis/F-9331-2011; CPRD, CPRD/B-9594-2017; OI Joffe, Steven/0000-0002-0667-7384 FU NHLBI NIH HHS [T32 HL 07574-19, HL 04184] NR 18 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2001 VL 33 IS 5 BP 582 EP 587 DI 10.1097/00005176-200111000-00013 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 502LK UT WOS:000172744900013 PM 11740233 ER PT J AU Jones, M Campbell, KA Duggan, C Young, G Bousvaros, A Higgins, L Mullen, E AF Jones, M Campbell, KA Duggan, C Young, G Bousvaros, A Higgins, L Mullen, E TI Multiple micronutrient deficiencies in a child fed an elemental formula SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article AB Children with developmental disabilities are at risk for malnutrition as a result of oropharyngeal dysphagia, interactions between nutrients and medications, altered energy and nutrient requirements, and their reliance on others to feed them. Several studies have documented alterations in weight and height parameters in these children (1). Recently, technologic advances such as percutaneous gastrostomy tube placement have significantly improved the nutritional status of many of these patients. In addition, a variety of proprietary formulas are being increasingly used to provide these patients with nutritional support. We describe a patient with developmental delay who received an elemental formula through a gastrostomy tube and who, despite normal energy balance and macronutrient status, developed signs and symptoms consistent with scurvy. He had severe vitamin C deficiency and deficiencies of vitamin A and zinc. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Mullen, E (reprint author), Dana Farber Canc Inst, Div Pediat Hematol & Oncol, Dana 3,44 Binney St, Boston, MA 02115 USA. NR 11 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 2001 VL 33 IS 5 BP 602 EP 605 DI 10.1097/00005176-200111000-00016 PG 4 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 502LK UT WOS:000172744900016 PM 11740236 ER PT J AU Williams, RC Paquette, DW Offenbacher, S Adams, DF Armitage, GC Bray, K Caton, J Cochran, DL Drisko, CH Fiorellini, JP Giannobile, WV Grossi, S Guerrero, DA Johnson, GK Lamster, IB Magnusson, I Oringer, RJ Persson, GR Van Dyke, TE Wolff, LF Santucci, EA Rodda, BE Lessem, J AF Williams, RC Paquette, DW Offenbacher, S Adams, DF Armitage, GC Bray, K Caton, J Cochran, DL Drisko, CH Fiorellini, JP Giannobile, WV Grossi, S Guerrero, DA Johnson, GK Lamster, IB Magnusson, I Oringer, RJ Persson, GR Van Dyke, TE Wolff, LF Santucci, EA Rodda, BE Lessem, J TI Treatment of periodontitis by local administration of minocycline microspheres: A controlled trial SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE minocycline/therapeutic use; periodontitis/drug therapy; multi-center studies; planing; scaling ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; CYTOMEGALOVIRUS-INFECTION; ADULT PERIODONTITIS; DENTAL INFECTIONS; RISK-FACTOR; ASSOCIATION; ATHEROSCLEROSIS; INFLAMMATION; FIBRINOGEN AB Background: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. Methods: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. Results: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. Conclusions: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients. C1 Univ N Carolina, Sch Dent, Dept Periodontol, Chapel Hill, NC 27599 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Missouri, Kansas City, MO 64110 USA. Eastman Dent Ctr, Rochester, NY 14620 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ Louisville, Louisville, KY 40292 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. SUNY Coll Buffalo, Buffalo, NY 14222 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Univ Iowa, Iowa City, IA USA. Columbia Univ, New York, NY USA. Univ Florida, Gainesville, FL USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Washington, Seattle, WA 98195 USA. Boston Univ, Boston, MA 02215 USA. Univ Minnesota, Minneapolis, MN USA. OraPharma Inc, Warminster, PA USA. RP Williams, RC (reprint author), Univ N Carolina, Sch Dent, Dept Periodontol, CB 7450, Chapel Hill, NC 27599 USA. EM ray_willams@dentistry.unc.edu RI Persson, Rutger/H-4901-2014; OI Giannobile, William/0000-0002-7102-9746 NR 44 TC 108 Z9 116 U1 1 U2 15 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 EI 1943-3670 J9 J PERIODONTOL JI J. Periodont. PD NOV PY 2001 VL 72 IS 11 BP 1535 EP 1544 DI 10.1902/jop.2001.72.11.1535 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 496TC UT WOS:000172411700010 PM 11759865 ER PT J AU Penson, RT Joel, SP Clark, S Gloyne, A Slevin, ML AF Penson, RT Joel, SP Clark, S Gloyne, A Slevin, ML TI Limited phase I study of morphine-3-glucuronide SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE morphine; morphine-3-glucuronide; toxicity; pharmacokinetics ID HEALTHY-VOLUNTEERS; MORPHINE; MORPHINE-6-GLUCURONIDE; PHARMACOKINETICS; METABOLITES; RAT; GLUCURONIDES; BINDING; HUMANS; PAIN AB The toxicity of morphine-3-glucuronide (M3G) has been investigated in an open, uncontrolled, single-blinded, single dose study over a limited range of doses. Three cohorts each of three healthy volunteers received 7.5, 15, and 30 mg/70 kg intravenous (IV) M3G. Blood sampling was undertaken for the following 24 h. Subjective toxicity was recorded on visual analogue scales and plasma M3G concentrations measured by a specific HPLC assay. Virtually no effects and no change in cardiovascular or respiratory parameters were seen. The pharmacokinetics fitted a two-compartment model. The mean elimination half-life (+/-S.D.) of M3G was 1.66 (+/-0.47) h. Mean AUC standardized to a dose of 1 mg/70 kg was 228 (+/- 62) eta molL(-1).h. Mean M3G clearance was 169 (+/- 48) mLmin(-1) and the mean volume of distribution was 23.1 (+/-4.8) liters. At the doses investigated there were no clear neuroexcitatory effects, no opioid effects, and the pharmacokinetics were very similar to those of morphine-6-glucuronide (M6G). (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. St Bartholomews Hosp, Dept Med Oncol, London EC1A 7BE, England. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 640, Boston, MA 02114 USA. NR 32 TC 40 Z9 40 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD NOV PY 2001 VL 90 IS 11 BP 1810 EP 1816 DI 10.1002/jps.1131.abs PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 491JP UT WOS:000172105500013 PM 11745739 ER PT J AU Fiedler, J Simon, FR Iwahashi, M Murphy, RC AF Fiedler, J Simon, FR Iwahashi, M Murphy, RC TI Effect of peroxisome proliferator-activated receptor a activation on leukotriene B-4 metabolism in isolated rat hepatocytes SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID OMEGA-OXIDATION; PPAR-ALPHA; ADULT-RAT; IDENTIFICATION; INFLAMMATION; EXPRESSION; ETHANOL; 5-LIPOXYGENASE; DEGRADATION; CHEMOTAXIS AB Leukotriene B-4 (LTB4) is a potent mediator of inflammation that recruits granulocytes to the site of injury during the inflammatory response. The biological activity of LTB4 is terminated by its metabolism into inactive metabolites. Recent studies have suggested that LTB4 may have additional activity as an endogenous ligand for the transcription factor peroxisome proliferator-activated receptor alpha (PPAR alpha). Based on the data presented, a model was proposed in which LTB4 acts in a negative feedback manner by inducing the transcription of genes involved its own metabolism. In the present study the effect of PPAR alpha activation on LTB4 metabolism was directly investigated. Primary cultures of rat hepatocytes were treated with LTB4 or the PPAR alpha agonist WY-14,643, and LTB4 metabolism was assessed by measuring levels of LTB4 and the formation of LTB4 metabolites. In addition, the effect of PPARa activation on levels of acyl-CoA oxidase mRNA and expression of CYP4F proteins, which are specific omega -hydroxylases for LTB4, was determined. Treatment of hepatocytes with WY-14,643, but not LTB4, was found to increase acyl-CoA oxidase mRNA and enhance expression of rat hepatic CYP4F proteins and CYP4A1. Neither WY-14,643 nor LTB4 caused an increase of the basal levels of LTB4 metabolism, and no novel metabolites were observed. These results do not support the hypothesis that a pathway of negative feedback regulation of LTB4 metabolism involving PPAR alpha exists in hepatocytes, because activation of PPAR alpha by LTB4 or other PPAR alpha agonists did not correlate with an increase in LTB4 metabolism. C1 Natl Jewish Med & Res Ctr, Div Cell Biol, Denver, CO 80206 USA. Univ Colorado, Hlth Sci Ctr, Div Gastroenterol, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Murphy, RC (reprint author), Natl Jewish Med & Res Ctr, Div Cell Biol, 1400 Jackson St, Denver, CO 80206 USA. FU NHLBI NIH HHS [HL25785]; NIDDK NIH HHS [DK15851] NR 34 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2001 VL 299 IS 2 BP 691 EP 697 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 485PU UT WOS:000171764100035 PM 11602682 ER PT J AU Alge, C Baxter, RM Doyle, ME Moor, ACE Brissette, JL Ortel, B AF Alge, C Baxter, RM Doyle, ME Moor, ACE Brissette, JL Ortel, B TI PUVA downregulates whn expression in primary mouse keratinocytes SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE gene expression; 8-methoxypsoralen; ultraviolet A; keratinocyte ID IN-VITRO; TRANSGENIC MICE; DIFFERENTIATION; CELLS; 8-METHOXYPSORALEN; PSORIASIS; GROWTH; BIOAVAILABILITY; TRANSCRIPTION; ULTRAVIOLET AB Psoralen photochemotherapy (PUVA) is one of the most efficient treatment regimens for psoriasis and other skin diseases. In order to evaluate keratinocyte-specific PUVA effects, we investigated the impact of clinically relevant PUVA doses on whn, the 'nude' gene. This transcription factor plays an important role in epidermal homeostasis, and epidermal whn over-expression results in a psoriasis-like phenotype. We demonstrated a persistent down-regulation of whn mRNA 48-72 h after PUVA treatment but not after UVA alone. Using transgenic animals, we also demonstrated dose-dependent down-regulation of whn promoter activity. Finally, whn-null ('nude') keratinocytes were more resistant to PUVA-induced suppression of DNA synthesis than wild-type cells. Our results suggest that whn suppression may be involved in mediating the anti-proliferative effect of PUVA on keratinocytes. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA 02199 USA. Harvard Univ, Sch Med, Charlestown, MA 02199 USA. Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. RP Ortel, B (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD NOV 1 PY 2001 VL 64 IS 1 BP 75 EP 81 DI 10.1016/S1011-1344(01)00219-6 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 494WQ UT WOS:000172309200010 PM 11705733 ER PT J AU Chaudhri, B Hajjar, RJ Harding, SE Terracciano, CMN AF Chaudhri, B Hajjar, RJ Harding, SE Terracciano, CMN TI Effects of over-expression of SERCA2a on action potential duration, Ca2+ entry and sarcoplasmic reticulum Ca2+ content in rabbit ventricular myocytes SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract CT Scientific Meeting of the Physiological-Society CY SEP 05-07, 2001 CL UNIV BRISTOL, BRISTOL, ENGLAND SP Physiolog Soc HO UNIV BRISTOL C1 Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV PY 2001 VL 536 SU S BP 74P EP 74P PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 606ZP UT WOS:000178766200087 ER PT J AU Malament, KA Socransky, SS AF Malament, KA Socransky, SS TI Survival of Dicor glass-ceramic dental restorations over 16 years. Part III: Effect of luting agent and tooth or tooth-substitute core structure SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID COMPRESSIVE STRENGTH; FRACTURE-RESISTANCE; CROWNS; THICKNESS AB Statement of problem. The influence of different types of restorative design features on the long-term survival of Dicor glass-ceramic restorations is only partially understood. Purpose. This study examined the effect of different types of luting agents and preparation core structures on the survival of Dicor glass-ceramic restorations functioning in vivo. Material and methods. A total of 1444 Dicor glass-ceramic restorations were placed on the teeth of 417 adults. Failure was defined as a restoration that required remake because of material fracture. The survival of restorations of different types, with different luting agents and preparation core structures, was described with Kaplan-Meier survival functions. The significance of differences in survival between different tooth or tooth-substitute preparation core structures and different luting agents was determined with the log-rank test. Results. The probability of survival of a typical acid-etched Dicor restoration luted to gold preparation core structures was 91% at 16 years compared with 75% for dentin preparation core structures (P < .01). The survival of acid-etched Dicor restorations luted to dentin preparations,vas significantly better than nonacid-etched restorations luted to dentin. Acid-etched Dicor restorations luted with resin composite exhibited a more favorable survival function than those luted with glass ionomer P < .01) and zinc phosphate ( P < .05). Differences between restorations luted with glass ionomer or zinc phosphate agents were not significant. Conclusion. Acid-etched Dicor restorations luted to gold preparation core structures exhibited significantly better intraoral survival than restorations luted to dentin. Acid-etched Dicor restorations survived better than nonacid-etched restorations when luted to dentin preparations. Acid-etched Dicor restorations luted with resin composite exhibited more favorable survivor functions than restorations luted with glass ionomer or zinc phosphate agents. C1 Tufts Univ, Sch Dent Med, Boston, MA USA. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Malament, KA (reprint author), Tufts Univ, Sch Dent Med, Boston, MA USA. NR 25 TC 101 Z9 104 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD NOV PY 2001 VL 86 IS 5 BP 511 EP 519 DI 10.1067/mpr.2001.119415 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 499FZ UT WOS:000172561600009 PM 11725279 ER PT J AU Henry, C Mitropoulou, V New, AS Koenigsberg, HW Silverman, J Siever, LJ AF Henry, C Mitropoulou, V New, AS Koenigsberg, HW Silverman, J Siever, LJ TI Affective instability and impulsivity in borderline personality and bipolar II disorders: similarities and differences SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE borderline personality disorder; bipolar disorder; affective instability; affective intensity; aggression; impulsiveness ID DSM-III; DEPRESSION; INTERVIEW; RELIABILITY; COMORBIDITY; INTENSITY; BEHAVIOR; VALIDITY; TRAITS AB Objectives: many studies have reported a high degree of comorbidity between mood disorders, among which are bipolar disorders, and borderline personality disorder and some studies have suggested that these disorders are co-transmitted in families. However. few studies have compared personality traits between these disorders to determine whether there is a dimensional overlap between the two diagnoses. The aim of this study was to compare impulsivity, affective lability and intensity in patients with borderline personality and bipolar II disorder and in subjects with neither of these diagnoses. :Methods: patients with borderline personality but without bipolar disorder (n=29), patients with bipolar II disorder without borderline personality but with other personality disorders (n= 14), patients with both borderline personality and bipolar II disorder (n= 12), and patients with neither borderline personality nor bipolar disorder but other personality disorders (OPD: n=93) were assessed using the Affective Lability Scale (ALS), the Affect Intensity Measure (AIM), the Buss-Durkee Hostility Inventory (BDHI) and the Barratt Impulsiveness Scale (BIS-7B). Results: borderline personality patients had significantly higher ALS total scores (P <0.05) and bipolar II patients tended to have higher ALS scores than patients with OPD (P <0.06). On one of the ALS subscales, the borderline patients displayed significant higher affective lability between euthymia and anger (P <0.002), whereas patients with bipolar II disorder displayed affective lability between euthymia and depression (P <0.04), or elation (P <0.01) or between depression and elation (P < 0.01). A significant interaction between borderline personality and bipolar II disorder was observed for lability between anxiety and depression (P <0.01) with the ALS. High scores for impulsiveness (BISTOT, P <0.001) and hostility (BDHL P <0.05) were obtained for borderline personality patients only and no significant interactions between diagnoses were observed. Only borderline personality patients tended to have higher affective intensity (AIM, P <0.07). Conclusions: borderline personality disorder and bipolar II disorder appear to involve affective lability, which may account for the efficacy of mood stabilizers treatments in both disorders. However, our results suggest that borderline personality disorder cannot be viewed as an attenuated group of affective disorders. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Ctr Hosp Charles Perrens, Serv Univ Psychiat, F-33076 Bordeaux, France. Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. INSERM, U394, F-33077 Bordeaux, France. RP Siever, LJ (reprint author), Bronx Vet Adm Med Ctr, 116A,130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NCRR NIH HHS [5 M01 RR00071]; NIMH NIH HHS [R01-MH-41131] NR 39 TC 213 Z9 219 U1 1 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD NOV-DEC PY 2001 VL 35 IS 6 BP 307 EP 312 DI 10.1016/S0022-3956(01)00038-3 PG 6 WC Psychiatry SC Psychiatry GA 502EU UT WOS:000172731400001 PM 11684137 ER PT J AU Ring, D McKee, MD Perey, BH Jupiter, JB Moody, P AF Ring, D McKee, MD Perey, BH Jupiter, JB Moody, P TI The use of a blade plate and autogenous cancellous bone graft in the treatment of ununited fractures of the proximal humerus SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID FIXATION AB Stable internal fixation is essential to obtain healing of an ununited fracture of the proximal humerus. Standard plate and screw fixation may be inadequate to secure a small, osteopenic proximal fragment. We used blade plates and autogenous cancellous bone graft to repair ununited fractures of the proximal humerus in 25 patients (19 women and 6 men) with a mean age of 61 years. Healing was documented in 23 of 25 patients (92%). Objective and subjective instruments documented substantial functional improvement in patients with healed fractures. The results were classified as good or excellent in 20 of 25 patients, and few complications were encountered. Blade plate fixation facilitates successful treatment of ununited fractures of the proximal humerus. C1 Massachusetts Gen Hosp, Hand Surg Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed, Boston, MA 02115 USA. Univ Toronto, St Michaels Hosp, Div Orthoped, Dept Surg, Toronto, ON M5B 1W8, Canada. Eagle Ridge Hosp, Port Moody, BC, Canada. RP Ring, D (reprint author), Massachusetts Gen Hosp, Hand Surg Serv, Dept Orthopaed Surg, ACC 525,15, Boston, MA 02114 USA. NR 20 TC 31 Z9 34 U1 1 U2 2 PU MOSBY, 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 NOV-DEC PY 2001 VL 10 IS 6 BP 501 EP 507 DI 10.1067/mse.2001.118414 PG 7 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 505LG UT WOS:000172913800001 PM 11743526 ER PT J AU Warner, JJP Parsons, IM AF Warner, JJP Parsons, IM TI Latissimus dorsi tendon transfer: A comparative analysis of primary and salvage reconstruction of massive, irreparable rotator cuff tears SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID REPAIR AB On the basis of a modified Constant scoring system, we compared outcomes for 16 patients who underwent latissimus dorsi transfer as a salvage reconstruction for a failed prior rotator cuff repair with outcomes for 6 patients who underwent a primary reconstruction for an irreparable cuff defect. There was a statistically significant difference in Constant score between groups, which measured 55% for the salvage group compared with 70% for the primary group (P < .05). Poor tendon quality, stage 4 muscle fatty degeneration, and detachment of the deltoid insertion each had a statistically significant effect on the Constant score (P < .05). Late rupture of the tendon transfer occurred in 44% of patients in the salvage group compared with 17% in the primary group at a mean of 19 months postoperatively. Rupture had a statistically significant effect on the Constant score, which declined by a mean of 14% (P < .05). We conclude that salvage reconstruction of failed prior rotator cuff repairs yields more limited gains in satisfaction and function than primary latissimus dorsi transfer. C1 Harvard Univ, Shoulder Serv, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Dept Orthopaed Surg, Pittsburgh, PA 15260 USA. RP Warner, JJP (reprint author), Harvard Univ, Shoulder Serv, Massachusetts Gen Hosp, Profess Off Bldg,Suite 403,275 Cambridge St, Boston, MA 02114 USA. NR 21 TC 101 Z9 102 U1 0 U2 4 PU MOSBY, 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 NOV-DEC PY 2001 VL 10 IS 6 BP 514 EP 521 DI 10.1067/mse.2001.118629 PG 8 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 505LG UT WOS:000172913800003 PM 11743528 ER PT J AU Bradley, KA Maynard, C Kivlahan, DR McDonell, MB Fihn, SD AF Bradley, KA Maynard, C Kivlahan, DR McDonell, MB Fihn, SD CA Ambulatory Care Quality Improvemen TI The relationship between alcohol screening questionnaires and mortality among male veteran outpatients SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID IDENTIFICATION TEST AUDIT; PRIMARY-CARE PATIENTS; ALL-CAUSE MORTALITY; USE DISORDERS; CONSUMPTION QUESTIONS; PROBLEM DRINKING; ADULTS; CAGE; POPULATION; WOMEN AB Objective: This study evaluated whether responses to alcohol screening questionnaires predicted mortality in a Department of Veterans Affairs (VA) primary care population. Method: This study involved 5,703 male outpatients (mean age = 64) who were enrolled in General Internal Medicine clinics at three Veterans Affairs (VA) medical centers and returned mailed questionnaires in 1993-94. The two questionnaires included the CAGE and Alcohol Use Disorders Identification Test (AUDIT) alcohol screening tests. Mortality was ascertained using the VA Beneficiary Identification and Record Locator System. Five-year crude and adjusted mortality rates were calculated for patients who screened positive and patients who screened negative on each alcohol screening test. Results: The risk of mortality was increased among drinkers who scored greater than or equal to8 on the full AUDIT (hazard ratio: 1.47; 95% confidence interval [Cl]: 1.08-2.00) or the three AUDIT consumption questions (1.59; 1.11-2.27), after adjusting for age, smoking, sociodemographic characteristics and chronic illnesses. The risk of mortality was also increased among drinkers who reported drinking greater than or equal to3 drinks daily (1.69; 1.28-2.22) or prior alcohol treatment (1.66; 1.27-2.17), in "fully adjusted" models. A positive CAGE score ( greater than or equal to2) was associated with significantly increased risk of mortality among drinkers in a model adjusted only for age and smoking (1.27; 1.02-1.58). Among nondrinkers, neither a positive CAGE score ( greater than or equal to2) nor report of prior alcohol treatment was associated with increased risk of mortality. Conclusions: VA outpatients who reported drinking during the previous year and who had a positive result on an alcohol screening test experienced higher mortality over the subsequent 5 years than did patients who screened negative. C1 VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. RP Bradley, KA (reprint author), VA Puget Sound Hlth Care Syst, NW Hlth Serv Res & Dev Ctr Excellence, Mail Stop 152,1660 S Columbian Way, Seattle, WA 98108 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU NIAAA NIH HHS [K23 AA00313] NR 25 TC 29 Z9 29 U1 1 U2 1 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD NOV PY 2001 VL 62 IS 6 BP 826 EP 833 PG 8 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 517JU UT WOS:000173608000016 PM 11838920 ER PT J AU Baskaran, H Toner, M Yarmush, ML Berthiaume, F AF Baskaran, H Toner, M Yarmush, ML Berthiaume, F TI Poloxamer-188 improves capillary blood flow and tissue viability in a cutaneous burn wound SO JOURNAL OF SURGICAL RESEARCH LA English DT Article ID RHEOTHRX INJECTION; THERMAL-INJURY; REPERFUSION; PERMEABILITY; REDUCTION; ADHERENCE; MODEL; SKIN AB After cutaneous burn injury, an area of tissue 1-2 min thick surrounding the wound is the site of a pronounced inflammatory response where blood flow is reduced. This "zone of stasis" undergoes progressive necrosis within 24-48 h, resulting in an expansion of the burn wound. Poloxamer-188 (P-188) is a surfactant that has been shown to prevent cell death due to electrical injury in vivo and heat shock in vitro. In this study, we investigated the effect of P-188 on blood flow within and around a burn wound and on the expansion of the wound area within 24 h after administration of a full-thickness burn injury. Results show that immediately (0-2 h) after the burn, red blood cell speed decreased to zero in a zone extending up to 1 min from the center of the burn in both P-188 (200 mg/kg)- and saline (0.9%)-treated animals. Between 1 and 3 min from the center of the burn, red blood cell speed decreased to 50% of preburn levels in saline controls (n = 5), while no decrease occurred in P-188-treated animals (n = 5). Beyond 3 min from the center of the burn, red blood speed was equal to the preburn levels in saline controls, while it increased by about 10% in P-188 animals. Twenty-four hours after administration of burn, the "zero red blood cell speed zone," termed as the zone of coagulation, became smaller in P-188-treated animals, with an area of 2.4 +/- 0.5 mm(2) (n = 5) compared to 3.5 +/- 0.5 mm(2) (n = 4) in saline controls (P < 0.01). These results suggest that P-188 prevented the formation of a zone of stasis within 24 h after the burn injury and reduced the area of coagulation observed 24 h after cutaneous burn injury. (C) 2001 Academic Press. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Berthiaume, F (reprint author), 51 Blossom St, Boston, MA 02114 USA. NR 24 TC 24 Z9 25 U1 1 U2 4 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 NOV PY 2001 VL 101 IS 1 BP 56 EP 61 DI 10.1006/jsre.2001.6262 PG 6 WC Surgery SC Surgery GA 490KQ UT WOS:000172051400009 PM 11676555 ER PT J AU Bloomstone, J Isaacson, K AF Bloomstone, J Isaacson, K TI If an operative complication occurs and no one reports it, does it really occur? SO JOURNAL OF THE AMERICAN ASSOCIATION OF GYNECOLOGIC LAPAROSCOPISTS LA English DT Editorial Material ID AIR-EMBOLISM; GAS EMBOLISM; HYSTEROSCOPY C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Reprod Endocrinol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Isaacson, K (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Dept Reprod Endocrinol, 15 Parkman St,Suite 231, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL AMER ASSOC GYNECOLOGIC LAPAROSCOPISTS PI SANTA FE SPRINGS PA 13021 EAST FLORENCE AVE, SANTA FE SPRINGS, CA 90670-4505 USA SN 1074-3804 J9 J AM ASSOC GYN LAP JI J. Am. Assoc. Gynecol. Laparoscopists PD NOV PY 2001 VL 8 IS 4 BP 467 EP 469 DI 10.1016/S1074-3804(05)60604-4 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 551RD UT WOS:000175574300001 PM 11677320 ER PT J AU Watts, D Damasco-Ty, E Ryan, F Goodman, B AF Watts, D Damasco-Ty, E Ryan, F Goodman, B TI Geriatricians Health Survey 2000 SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE geriatrician; vitamin supplements; behavior ID CARDIOVASCULAR-DISEASE; MULTIVITAMIN USE; UNITED-STATES; OLDER ADULTS; PHYSICIANS; STROKE; WOMEN; RISK; SUPPLEMENTATION; ANTIOXIDANTS AB OBJECTIVES: To characterize geriatricians' preventive health behaviors including vitamin/supplement use, exercise, smoking, alcohol use, and weight control. DESIGN: Mailed questionnaire. SETTING: United States. PARTICIPANTS: Two thousand six hundred eleven U.S. physicians certified as having added qualifications in geriatric medicine and who were members in the American Geriatrics Society; 1,524 returned completed questionnaires (58%). MEASUREMENTS: Rates of supplement use and recommendations, preventive health visits, advance directive completion, exercise, religious service attendance, smoking, alcohol use, and amount of adult weight gain. RESULTS: Most responding geriatricians took at least one vitamin supplement: 50% vitamin E, 50% a multivitamin (MVI), and 31% vitamin C. Calcium ingestion was common among women. Other supplement use was uncommon: ginkgo compounds were consumed by 47 (3%), and 77 (5%) took a variety of other nonvitamin supplements. Over 90% recommended vitamins, especially multivitamins and vitamin E, at least sometimes. Recommendations for ginkgo (38%) and St. John's wort (33%) were also common. Almost half of respondents had completed a formal advance directive. Exercise was practiced at least weekly by 88%. Cigarette smoking was rare (1%), but at least occasional alcohol use was common (85%). Most of respondents were men (74%), and 35% had completed fellowship training. CONCLUSION: Vitamin/supplement use was common among responding geriatricians but not universal. Respondents often recommended MVI, vitamin E, and vitamin C, but were less likely to consume or recommend other supplements. The most common preventive health behavior among our respondents was exercise. C1 Univ Wisconsin, Sch Med, Dept Med, Sect Geriatr & Gerontol, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Watts, D (reprint author), Univ Wisconsin, Sch Med, Dept Med, Sect Geriatr & Gerontol, 2870 Univ Ave,Suite 100, Madison, WI 53705 USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2001 VL 49 IS 11 BP 1535 EP 1538 DI 10.1046/j.1532-5415.2001.4911250.x PG 4 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 490MF UT WOS:000172055100019 PM 11890595 ER PT J AU Hazzard, WR AF Hazzard, WR TI What heterogeneity among centenarians can teach us about genetics, aging, and longevity SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID APOLIPOPROTEIN-E; E PHENOTYPES; DYSBETALIPOPROTEINEMIA; POLYMORPHISM; DISEASE C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Hazzard, WR (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2001 VL 49 IS 11 BP 1568 EP 1569 DI 10.1046/j.1532-5415.2001.4911256.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 490MF UT WOS:000172055100026 PM 11890602 ER PT J AU Binder, LM Storzbach, D Campbell, KA Rohlman, DS Anger, WK AF Binder, LM Storzbach, D Campbell, KA Rohlman, DS Anger, WK CA Portland Env Hazards Res Center TI Neurobehavioral deficits associated with chronic fatigue syndrome in veterans with Gulf War unexplained illnesses SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE chronic fatigue syndrome; cognitive function; Gulf War unexplained illnesses ID SYMPTOMS; PERFORMANCE; COMPUTER AB Gulf War unexplained illnesses (GWUI) are a heterogeneous collection of symptoms of unknown origin known to be more common among veterans of the Gulf War than among nonveterans. In the present study we focused on one of these unexplained il I nesses, We tested the hypothesis that in a sample of Persian Gulf War veterans chronic fatigue syndrome (CFS) was associated with cognitive deficits on computerized cognitive testing after controlling for the effects of premorbid cognitive differences. We obtained Armed Forces Qualification Test (AFQT) data acquired around the date of induction into the military on 94 veterans of the Gulf War, 32 with CFS and 62 healthy controls. Controls performed better than participants diagnosed with CFS on the AFQT. Cognitive deficits were associated with CFS on 3 of 8 variables after the effect of premorbid AFQT scores was removed with ANCOVA. C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Binder, LM (reprint author), 4900 SW Griffith Dr,Suite 244, Beaverton, OR 97005 USA. NR 20 TC 16 Z9 16 U1 3 U2 6 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD NOV PY 2001 VL 7 IS 7 BP 835 EP 839 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 496YV UT WOS:000172426700006 PM 11771626 ER PT J AU Zietman, AL Thakral, H Wilson, L Schellhammer, P AF Zietman, AL Thakral, H Wilson, L Schellhammer, P TI Conservative management of prostate cancer in the prostate specific antigen era: The incidence and time course of subsequent therapy SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostate-specific antigen; survival ID EXPECTANT MANAGEMENT; NATURAL-HISTORY; DIAGNOSIS AB Purpose: The long natural history of early stage prostate cancer is well recognized and a conservative approach to the treatment of elderly men is often encouraged. We assessed the ability of patients and physicians to adhere to a policy of watchful waiting in the prostate specific antigen (PSA) era. Materials and Methods: We retrospectively reviewed the records of all 199 men with stages T1-2 prostate cancer and PSA less than 20 ng./ml. who in our practice elected watchful waiting. Median followup in the population overall was 3.4 years. We performed Kaplan-Meier actuarial analysis of overall and disease specific survival, and most pertinent survival free from therapy. A questionnaire was administered to record the attitude of patients who ultimately proceeded to treatment to determine how therapy was triggered. Results: Median patient age was 71 years and median PSA was 6.6 ng./ml. The tumor was impalpable in 52% of patients, Gleason sum was 6 or less in 80% and 11% used some form of herbal remedy or nutritional supplementation. Of the 37 men who died during observation, including 35 of co-morbid illness, only 6 underwent treatment. Overall survival at 5 and 7 years was 77% and 63% but disease specific survival was 98% and 98%, respectively. A total of 64 patients underwent treatment and actuarial freedom from treatment was 56% at 5 years, including 51% and 73% in those younger and older than 75 years at diagnosis. The likelihood of being alive and free from treatment was 43% at 5 years and 26% at 7. Of the 63 men treated 48 (76%) underwent radical therapy (brachytherapy in 17, external beam radiotherapy in 29 and prostatectomy in 2), while only 24% received androgen deprivation. The median PSA increase from diagnosis to treatment in treated patients was 2.9 ng./ml., and it was 0.9 ng./ml. from diagnosis to the last followup in those not treated. Of the treated patients 81% believed that the physician had initiated therapy due to a PSA increase or a nodule. However, physicians recorded having advocated treatment in only 24% of cases. Conclusions: When patients do not die of co-morbid illness, they are likely to proceed to therapy well within the first decade after diagnosis (57% by 5 years and 74% by 7). Therapy was usually definitive (radical) and triggered by slight, inevitable PSA increases. The patient perception was that the physicians initiated therapy in response to increasing PSA. However, the physicians more often perceived that treatment was initiated by patients. Therefore, watchful waiting in the PSA era often represents radical therapy delayed by a few years. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Sentara Canc Ctr Inst, Dept Urol, Norfolk, VA USA. Sentara Canc Ctr Inst, Virginia Prostate Ctr, Norfolk, VA USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. RP Zietman, AL (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, 100 Blossom St,COX 302, Boston, MA 02114 USA. NR 17 TC 51 Z9 52 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 NOV PY 2001 VL 166 IS 5 BP 1702 EP 1706 DI 10.1016/S0022-5347(05)65657-1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 481YC UT WOS:000171547200022 PM 11586206 ER PT J AU Paige, NM Hays, RD Litwin, MS Rajfer, J Shapiro, MF AF Paige, NM Hays, RD Litwin, MS Rajfer, J Shapiro, MF TI Improvement in emotional well-being and relationships of users of sildenafil SO JOURNAL OF UROLOGY LA English DT Article DE impotence; quality of life; questionnaires ID QUALITY-OF-LIFE; ERECTILE DYSFUNCTION; INDEX; MEN AB Purpose: We estimated the association of sildenafil use with erectile function, relationship with sexual partner, functional status and emotional well-being in men with erectile dysfunction. Materials and Methods: Letters were mailed to eligible patients at a university hospital urology and internal medicine clinic, and university affiliated community primary care clinics by the primary care provider or urologist inviting them to participate in the study. Of the eligible sample 124 men (53%) completed and returned a survey, including 85 who reported current sildenafil use. Change scores in these patients were calculated using the International Index of Erectile Function, marital interaction scale from the Cancer Rehabilitation Evaluation System Short Form, 5-item emotional well-being scale of the RAND 36-Item Health Survey and 12-Item Short Form Health Survey. Results: Sildenafil users reported an 88% increase in erectile function scores, 60% increase in overall sexual satisfaction and 36% increase in intercourse satisfaction related to the use of sildenafil (p <0.001). Of the respondents 38% indicated that using sildenafil had definitely improved quality of life. Likewise 29% of respondents indicated that using sildenafil had definitely improved the relationship with their partner. With sildenafil there was a statistically significant improvement in the scores of erectile and sexual function (p <0.001), sexual partner relationship (p = 0.007) and emotional well-being (p <0.001). In a multivariate model improved erectile function and sexual partner relationship were each significantly associated with improved emotional well-being (R-2 = 0.20, p <0.001). Conclusions: Sildenafil users reported significant improvements in erectile and sexual function that were associated with positive changes in emotional well-being and the sexual partner relationships with their sexual partner. C1 Univ Calif Los Angeles, Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA USA. RP Paige, NM (reprint author), Univ Calif Los Angeles, Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. RI Hays, Ronald/D-5629-2013 NR 22 TC 52 Z9 52 U1 1 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 NOV PY 2001 VL 166 IS 5 BP 1774 EP 1778 DI 10.1016/S0022-5347(05)65673-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 481YC UT WOS:000171547200041 PM 11586222 ER PT J AU Collins, MM O'Leary, MP Calhoun, EA Pontari, MA Adler, A Eremenco, S Chang, CH Odom, L Litwin, MS AF Collins, MM O'Leary, MP Calhoun, EA Pontari, MA Adler, A Eremenco, S Chang, CH Odom, L Litwin, MS CA Chronic Prostatitis Collaborative TI The Spanish National Institutes of Health-Chronic Prostatitis Symptom Index: Translation and linguistic validation SO JOURNAL OF UROLOGY LA English DT Article DE prostate; questionnaires; prostatitis; quality of life; translations ID FUNCTIONAL ASSESSMENT AB Purpose: The prominence of health related quality of life end points in international clinical research underscores the importance of well validated and translated measures to enable cross-cultural comparison. The National Institutes of Health (NIH)-Chronic Prostatitis Symptom Index (CPSI) assesses symptoms and health related quality of life in men with chronic nonbacterial, NIH type III prostatitis. To expand its use to Spanish speaking patients we performed a translation and linguistic validation. Materials and Methods: The 9-item NIH-CPSI was translated into Spanish according to a standard methodology of 2 forward translations, 1 reconciled version, back translation of the reconciled version and 3 independent reviews by bilingual experts. The purpose of this methodology was to create a single universal Spanish version that would be acceptable to native Spanish speakers inside and outside of the United States. After the translation process the Spanish version was pre-tested in Argentina, Mexico, Spain and the United States. Patient responses were analyzed to identify necessary modifications. The internal consistency of the CPSI was evaluated using Cronbach's alpha. Pearson's product moment correlations were used to evaluate construct validity. Results: Data were collected from chronic prostatitis patients, including 15 in Argentina, 15 in Mexico, 4 in the United States and 3 in Spain. The translation had high reliability overall and in all subscales (Cronbach's coefficient alpha = 0.81 to 0.94), and the subscales correlated well with each other (r = 0.76 to 0.97). However, patients expressed difficulty in distinguishing the response categories "a menudo" ("often") from "normalmente" ("usually") in question 3. We revised "a menudo" to "muchas veces" ("much of the time") and "normalmente" to "casi siempre" ("almost always") to improve the distinctiveness of response categories. Conclusions: The Spanish NIH-CPSI has high reliability as well as face and construct validity in Spanish speaking men from various countries. The Spanish NIH-CPSI permits cross-cultural comparisons of men with chronic nonbacterial prostatitis. C1 Massachusetts Gen Hosp, Div Gen Med, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Northwestern Univ, Inst Hlth Serv & Hlth Policy Studies, Chicago, IL 60611 USA. Evanston Northwestern Healthcare, Ctr Outcomes Res & Educ, Evanston, IL USA. Temple Univ, Sch Med, Dept Urol, Philadelphia, PA 19122 USA. Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Hlth Serv, Los Angeles, CA USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Div Gen Med, Med Serv, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01 DK53736, R01 DK53752, R01 DK53730, R01 DK53734, R01 DK53732, R01 DK53746] NR 10 TC 20 Z9 24 U1 1 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 NOV PY 2001 VL 166 IS 5 BP 1800 EP 1803 DI 10.1016/S0022-5347(05)65678-9 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 481YC UT WOS:000171547200046 PM 11586227 ER PT J AU McHutchison, JG Shad, JA Gordon, SC Morgan, TR Ling, MH Garaud, JJ Albrecht, JK Dienstag, JL AF McHutchison, JG Shad, JA Gordon, SC Morgan, TR Ling, MH Garaud, JJ Albrecht, JK Dienstag, JL TI Predicting response to initial therapy with interferon plus ribavirin in chronic hepatitis C using serum HCV RNA results during therapy SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE HCV; HCV RNA; interferon; prediction of nonresponse and response; ribavirin ID CONTROLLED TRIAL; VIRUS; INFECTION; MULTICENTER; COMBINATION; PLACEBO AB In patients with chronic hepatitis C, 48 weeks of therapy with interferon (IFN) plus ribavirin results in a sustained virologic response of 40%. Preliminary analysis suggests that measuring HCV RNA at week 24, rather than week 12, might provide the best prediction of treatment response. To assess the clinical utility of serum HCV RNA determinations at different times during therapy as a predictor of a sustained virologic response we evaluated 912 treatment-naive patients. Patients were randomized to receive IFN-alpha 2b, 3 million units (MU) three times weekly (tiw), for 24 or 48 weeks with either ribavirin or placebo, and then followed for 24 weeks. Serum HCV RNA was measured at weeks 4 and 12 in patients treated for 24 weeks; at 4, 12, and 24 weeks during therapy in those treated for 48 weeks, and week 24 post-therapy in all patients. Sustained response was defined as loss of serum HCV RNA at week 24 follow-up. Other patients were considered virologic nonresponders. For patients receiving 48 weeks of combination therapy, detectable serum HCV RNA at week 24 predicted nonresponse (positive predictive value) in 99% of patients compared to 89% at week 12. In patients treated for 24 weeks, testing at week 12 was more predictive of nonresponse than testing at week 4 in the combination-therapy croup but not in the monotherapy group. Hence, for combination therapy, testing for serum HCV RNA as a predictor of nonresponse is most accurate at week 24 of therapy; a positive test correctly identified 99% of nonresponders. C1 Scripps Clin, Div Gastroenterol & Hepatol, La Jolla, CA 92037 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Vet Affairs Med Ctr, Long Beach, CA USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP McHutchison, JG (reprint author), Scripps Clin, Div Gastroenterol & Hepatol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NCRR NIH HHS [MO1-RR00833, MO1-RR01006] NR 25 TC 43 Z9 44 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD NOV PY 2001 VL 8 IS 6 BP 414 EP 420 DI 10.1046/j.1365-2893.2001.00312.x PG 7 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 495LG UT WOS:000172342200004 PM 11703572 ER PT J AU Gorry, PR Bristol, G Zack, JA Ritola, K Swanstrom, R Birch, CJ Bell, JE Bannert, N Crawford, K Wang, H Schols, D De Clercq, E Kunstman, K Wolinsky, SM Gabuzda, D AF Gorry, PR Bristol, G Zack, JA Ritola, K Swanstrom, R Birch, CJ Bell, JE Bannert, N Crawford, K Wang, H Schols, D De Clercq, E Kunstman, K Wolinsky, SM Gabuzda, D TI Macrophage tropism of human immunodeficiency virus type 1 isolates from brain and lymphoid tissues predicts neurotropism independent of coreceptor specificity SO JOURNAL OF VIROLOGY LA English DT Review ID MONOCYTE-DERIVED MACROPHAGES; CHEMOKINE RECEPTORS CCR3; PROTEIN-COUPLED RECEPTOR; CENTRAL-NERVOUS-SYSTEM; HIV-1 ENTRY; DIVERSE HUMAN; IN-VIVO; V3 LOOP; BIOLOGICAL CHARACTERIZATION; ANTIRETROVIRAL THERAPY AB The viral determinants that underlie human immunodeficiency virus type 1 (HIV-1) neurotropism are unknown, due in part to limited studies on viruses isolated from brain. Previous studies suggest that brain-derived viruses are macrophage tropic (M-tropic) and principally use CCR5 for virus entry. To better understand HIV-1 neurotropism, we isolated primary viruses from autopsy brain, cerebral spinal fluid, blood, spleen, and lymph node samples from AIDS patients with dementia and HIV-1 encephalitis. Isolates were characterized to determine coreceptor usage and replication capacity in peripheral blood mononuclear cells (PBMC), monocyte-derived macrophages (MDM), and microglia. Env V1/V2 and V3 heteroduplex tracking assay and sequence analyses were performed to characterize distinct variants in viral quasispecies. Viruses isolated from brain, which consisted of variants that were distinct from those in lymphoid tissues, used CCR5 (R5), CXCR4 (X4), or both coreceptors (R5X4). Minor usage of CCR2b, CCR3, CCR8, and Apj was also observed. Primary brain and lymphoid isolates that replicated to high levels in MDM showed a similar capacity to replicate in microglia. Six of 11 R5 isolates that replicated efficiently in PBMC could not replicate in MDM or microglia due to a block in virus entry. CD4 overexpression in microglia transduced with retroviral vectors had no effect on the restricted replication of these virus strains. Furthermore, infection of transfected cells expressing different amounts of CD4 or CCR5 with M-tropic and non-M-tropic R5 isolates revealed a similar dependence on CD4 and CCR5 levels for entry, suggesting that the entry block was not due to low levels of either receptor. Studies using TAK-779 and AMD3100 showed that two highly M-tropic isolates entered microglia primarily via CXCR4. These results suggest that HIV-1 tropism for macrophages and microglia is restricted at the entry level by a mechanism independent of coreceptor specificity. These findings provide evidence that M-tropism rather than CCR5 usage predicts HIV-1 neurotropism. 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 Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA 90024 USA. Univ N Carolina, Chapel Hill, NC USA. Victorian Infect Dis Reference Lab, Melbourne, Vic, Australia. Univ Edinburgh, Dept Pathol, Edinburgh, Midlothian, Scotland. Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JF816, Boston, MA 02115 USA. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NCI NIH HHS [CA79458]; NIAID NIH HHS [AI28691, AI28697, AI36059, AI36554, AI44667, P30 AI028691, P30 AI028697, R01 AI036554, R01 AI044667, R37 AI036059, R37 AI044667, T32 AI007419, T32-AI07419, U01 AI035039, U01 AI35039]; NICHD NIH HHS [HD37260]; NIDA NIH HHS [DA13127]; NINDS NIH HHS [R01 NS037277, NS35734, NS37277, R01 NS035734] NR 110 TC 207 Z9 211 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2001 VL 75 IS 21 BP 10073 EP 10089 DI 10.1128/JVI.75.21.10073-10089.2001 PG 17 WC Virology SC Virology GA 480DZ UT WOS:000171447900007 PM 11581376 ER PT J AU Montefiori, DC Hill, TS Vo, HTT Walker, BD Rosenberg, ES AF Montefiori, DC Hill, TS Vo, HTT Walker, BD Rosenberg, ES TI Neutralizing antibodies associated with viremia control in a subset of individuals after treatment of acute human immunodeficiency virus type 1 infection SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1/SIV CHIMERIC VIRUS; IMMUNE-RESPONSES; T-LYMPHOCYTES; HIV; COMBINATION; MACAQUES; SEROCONVERSION; ZIDOVUDINE; LAMIVUDINE AB Immediate treatment of acute human immunodeficiency virus type 1 (HIV-1) infection has been associated with subsequent control of viremia in a subset of patients after therapy cessation, but the immune responses contributing to control have not been fully defined. Here we examined neutralizing antibodies as a correlate of viremia control following treatment interruption in HIV-1-infected individuals in whom highly active antiretriviral therapy (HAART) was initiated during early seroconversion and who remained on therapy for 1 to 3 years. Immediately following treatment interruption, neutralizing antibodies were undetectable with T-cell-line adapted, strains and the autologous primary HIV-1 isolate in seven of nine subjects. Env- and Gag-specific antibodies as measured by enzyme-linked immunosorbent assay were also low or undetectable at this time. Despite this apparent poor maturation of the virus-specific B-cell response during HAART, autologous neutralizing antibodies emerged rapidly and correlated with a spontaneous downregulation in rebound viremia following treatment interruption in three subjects. Control of rebound viremia was seen in other subjects in the absence of detectable neutralizing antibodies. The results indicate that virus-specific B-cell priming occurs despite the early institution of HAART, allowing rapid secondary neutralizing-antibody production following treatment interruption in a subset of individuals. Since early HAART limits viral diversification, we hypothesize that potent neutralizing-antibody responses to autologous virus are able to mature and that in some persons these responses contribute to the control of plasma viremia after treatment cessation. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Montefiori, DC (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2926, Durham, NC 27710 USA. FU NIAID NIH HHS [AI01541, AI40237] NR 39 TC 73 Z9 76 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2001 VL 75 IS 21 BP 10200 EP 10207 DI 10.1128/JVI.75.21.10200-10207.2001 PG 8 WC Virology SC Virology GA 480DZ UT WOS:000171447900019 PM 11581388 ER PT J AU Veazey, RS Gauduin, MC Mansfield, KG Tham, IC Altman, JD Lifson, JD Lackner, AA Johnson, RP AF Veazey, RS Gauduin, MC Mansfield, KG Tham, IC Altman, JD Lifson, JD Lackner, AA Johnson, RP TI Emergence and kinetics of simian immunodeficiency virus-specific CD8(+) T cells in the intestines of macaques during primary infection SO JOURNAL OF VIROLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; CYTOTOXIC LYMPHOCYTES-T; PRIMARY IMMUNE-RESPONSE; RHESUS-MONKEYS; DISEASE PROGRESSION; PERIPHERAL-BLOOD; SIV INFECTION; CEREBROSPINAL-FLUID; PATHOGENIC SIV; PLASMA VIREMIA AB In this report, three Mamu-A*01(+) rhesus macaques were examined to compare the emergence of simian immunodeficiency virus (SIV)-specific CD8(+) T cells in the intestines and blood in early SIV infection using a major histocompatibility complex class I tetramer complexed with the Gag(181-189) peptide. Fourteen days after intravenous inoculation with SIVmac251, large numbers of SrV Gag(181-189)-specific CD8(+) T cells were detected in the intestinal mucosa (3.1 to 11.5% of CD3(+) CD8(+) lymphocytes) as well as in the blood (3.1 to 13.4%) of all three macaques. By 21 days postinoculation, levels of tetramer-binding cells had dropped in both the intestines and blood. At day 63, however, levels of SIV Gag(181-189)- specific CD8(+) T cells in the intestines had rebounded in all three macaques to levels that were higher (8.6 to 18.7%) than those at day 21. In contrast, percentages of tetramer-binding cells in the peripheral blood remained comparatively stable (2.5 to 4.5%) at this time point. In summary, SFV Gag(181-189)-specific CD8(+) T cells appeared in both the intestinal mucosa and peripheral blood at a comparable rate and magnitude in primary SIV infection. Given that the intestine is a major site of early viral replication as well as the site where most of the total body lymphocyte pool resides, these data indicate that it is also an early and important site of development of antiviral immune responses. C1 Tulane Univ, Tulane Reg Primate Res Ctr, Covington, LA 70433 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Emory Univ, Sch Med, Emory Vaccine Ctr Yerkes, Atlanta, GA 30322 USA. NCI, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Veazey, RS (reprint author), Tulane Univ, Tulane Reg Primate Res Ctr, 18703 3 Rivers Rd, Covington, LA 70433 USA. FU NCI NIH HHS [N01-CO-56000]; NCRR NIH HHS [P51 RR000168, RR00168, K26 RR000168]; NIAID NIH HHS [AI45314, AI49080, R01 AI049080]; NICHD NIH HHS [HD36310]; NIDDK NIH HHS [DK50550, R01 DK050550] NR 39 TC 51 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2001 VL 75 IS 21 BP 10515 EP 10519 DI 10.1128/JVI.75.21.10515-10519.2001 PG 5 WC Virology SC Virology GA 480DZ UT WOS:000171447900054 PM 11581423 ER PT J AU Bannert, N Farzan, M Friend, DS Ochi, H Price, KS Sodroski, J Boyce, JA AF Bannert, N Farzan, M Friend, DS Ochi, H Price, KS Sodroski, J Boyce, JA TI Human mast cell progenitors can be infected by macrophagetropic human immunodeficiency virus type 1 and retain virus with maturation in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID DENDRITIC CELLS; HIV-INFECTION; LYMPH-NODES; CCR5; RECEPTORS; CXCR4; DIFFERENTIATION; REPLICATION; MONOCYTES; MICROGLIA AB Mast cells are critical components of innate and adaptive immunity that differentiate in tissues in situ from circulating committed progenitor cells. We now demonstrate that human cord blood-derived mast cell Progenitors are susceptible to infection with macrophagetropic (M-tropic) and dualtropic human immunodeficiency virus type 1 (HIV-1) isolates but not with T-cell-tropic (T-tropic) strains. Mast cell progenitors (c-kit(+) CD13(+) cells with chloroacetate esterase activity) were purified from 4-week-old cultures of cord blood mononuclear cells maintained in stem cell factor, interleukin-6 (IL-6), and IL-10 using a CD14 depletion column. These progenitors expressed CCR3, CCR5, and CXCR4, as well as low levels of CD4. When infected in vitro with viruses pseudotyped with different HIV and simian immunodeficiency virus envelope glycoproteins, only M-tropic and dualtropic, but not T-tropic, viruses were able to enter mast cell progenitors. Both the CCR5-specific monoclonal antibody 2D7 and TAK-779, a nonpeptide inhibitor of CCR5-mediated viral entry, blocked HIV-1 strain ADA infection by > 80%. Cultures infected with replication-competent virus produced progressively increasing amounts of virus for 21 days as indicated by p24 antigen detection. Mast cell progenitors that were exposed to an M-tropic, green fluorescent protein-expressing HIV-1 strain exhibited fluorescence indicative of viral entry and replication on a single-cell level and retained virus production during differentiation. The trafficking of mast cell progenitors to multiple tissues, combined with the long life span of mature mast cells, suggests that they could provide a widespread and persistent HIV reservoir in AIDS. C1 Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Partners Asthma Ctr, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Boyce, JA (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Smith Bldg,Rm 618,1 Jimmy Fund Way, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-36110, P01 HL036110]; NIAID NIH HHS [AI-01305, AI-22531, AI-31599, P01 AI031599, U19 AI031599] NR 34 TC 51 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2001 VL 75 IS 22 BP 10808 EP 10814 DI 10.1128/JVI.75.22.10808-10814.2001 PG 7 WC Virology SC Virology GA 483TV UT WOS:000171652700025 PM 11602722 ER PT J AU Hioe, CE Tuen, M Chien, PC Jones, G Ratto-Kim, S Norris, PJ Moretto, WJ Nixon, DF Gorny, MK Zolla-Pazner, S AF Hioe, CE Tuen, M Chien, PC Jones, G Ratto-Kim, S Norris, PJ Moretto, WJ Nixon, DF Gorny, MK Zolla-Pazner, S TI Inhibition of human immunodeficiency virus type 1 gp120 presentation to CD4 T cells by antibodies specific for the CD4 binding domain of gp120 SO JOURNAL OF VIROLOGY LA English DT Article ID ALLOGENEIC BONE-MARROW; ENVELOPE GLYCOPROTEIN; PROLIFERATIVE RESPONSES; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; CELLULAR-IMMUNITY; HIV-1 INFECTION; ANTIGEN; LYMPHOCYTE; INDIVIDUALS AB Human immunodeficiency virus (HIV)-specific CD4 T-cell responses, particularly to the envelope glycoproteins of the virus, are weak or absent in most HIV-infected patients. Although these poor responses can be attributed simply to the destruction of the specific CD4 T cells by the virus, other factors also appear to contribute to the suppression of these virus-specific responses. We previously showed that human monoclonal antibodies (MAbs) specific for the CD4 binding domain of gp120 (gp120(CD4BD)), when complexed with gp120, inhibited the proliferative responses of gp120-specific CD4 T-cells. MAbs to other gp120 epitopes did not exhibit this activity. The present study investigated the inhibitory mechanisms of the anti-gp120(CD4BD) MAbs. The anti-gp120(CD4BD) MAbs complexed with gp120 suppressed gamma interferon production as well as proliferation of gp120-specific CD4 T cells. Notably, the T-cell responses to gp120 were inhibited only when the MAbs were added to antigen-presenting cells (APCs) during antigen pulse; the addition of the MAbs after pulsing caused no inhibition. However, the anti-gp120(CD4BD) MAbs by themselves, or as MAb/gp120 complexes, did not affect the presentation of gp120-derived peptides by the APCs to T cells. These MAb/gp120 complexes also did not inhibit the ability of APCs to process and present unrelated antigens. To test whether the suppressive effect of anti-gp120(CD4BD) antibodies is caused by the antibodies' ability to block gp120-CD4 interaction, APCs were treated during antigen pulse with anti-CD4 MAbs. These treated APCs remained capable of presenting gp120 to the T cells. These results suggest that anti-gp120(CD4BD) Abs inhibit gp120 presentation by altering the uptake and/or processing of gp120 by the APCs but their inhibitory activity is not due to blocking of gp120 attachment to CD4 on the surface of APCs. C1 Vet Adm Med Ctr, New York, NY 10010 USA. NYU, Sch Med, New York, NY 10010 USA. Chelsea & Westminster Hosp, Dept Immunol, London SW10 0NH, England. Walter Reed Army Inst Res, Henry M Jackson Fdn, Rockville, MD 20850 USA. Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94141 USA. RP Hioe, CE (reprint author), Vet Adm Med Ctr, 423 E 23rd St,Room 18-124 N, New York, NY 10010 USA. RI Jones, Gareth/C-6270-2011; OI Nixon, Douglas/0000-0002-2801-1786 FU NHLBI NIH HHS [HL59725, R01 HL059725]; NIAID NIH HHS [AI 27742, AI43224, K08 AI001698, P30 AI027742] NR 37 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2001 VL 75 IS 22 BP 10950 EP 10957 DI 10.1128/JVI.75.22.10950-10957.2001 PG 8 WC Virology SC Virology GA 483TV UT WOS:000171652700038 PM 11602735 ER PT J AU Soares, CN Cohen, LS Otto, MW Harlow, BL AF Soares, CN Cohen, LS Otto, MW Harlow, BL TI Characteristics of women with premenstrual dysphoric disorder (PMDD) who did or did not report history of depression: A preliminary report from the Harvard Study of Moods and Cycles SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID SOCIAL-ADJUSTMENT; PHASE; FLUOXETINE; SYMPTOMS; SMOKING AB We examined the characteristics of 33 women with a diagnosis of premenstrual dysphoric disorder (PMDD) who did (n = 19) or did not (n = 14) report a history of major depression. Five hundred thirteen older premenopausal women (ages 36-44) from a community-based sample completed a prospective evaluation of PMDD with daily records. The diagnosis of PMDD was confirmed in 33 women (6.3%), and 14 subjects met criteria for PMDD with no history of depression. Demographic characteristics, cigarette smoking, and menstrual and reproductive history of subjects with PMDD who did or did not report a history of depression were compared. Women with PMDD and no history of depression were more educated and more frequently had a marital disruption (p < 0.05). No significant differences were observed with respect to reproduction-related characteristics or past cigarette smoking. These preliminary data suggest the existence of characteristics particularly related to women who meet criteria for PMDD and have no history of depression. Given the significant psychosocial impairment commonly associated with PMDD symptoms and the existing data that support its classification and adequate treatment as a distinct clinical entity, further studies are needed to better identify predictors of this syndrome unrelated to a lifetime history of depression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA USA. RP Soares, CN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. FU NIMH NIH HHS [R01-MH-50013] NR 24 TC 24 Z9 27 U1 3 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD NOV PY 2001 VL 10 IS 9 BP 873 EP 878 DI 10.1089/152460901753285778 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 500LY UT WOS:000172630100009 PM 11747682 ER PT J AU Covinsky, KE Eng, C Lui, LY Sands, LP Sehgal, AR Walter, LC Wieland, D Eleazer, GP Yaffe, K AF Covinsky, KE Eng, C Lui, LY Sands, LP Sehgal, AR Walter, LC Wieland, D Eleazer, GP Yaffe, K TI Reduced employment in caregivers of frail elders: Impact of ethnicity, patient clinical characteristics, and caregiver characteristics SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LONG-TERM-CARE; OLDER ADULTS; HEALTH; MODEL; PREFERENCES; DISABILITY; PREVALENCE; FAMILIES; DEMENTIA; COSTS AB Background. Without family caregivers, many frail elders who live at home would require nursing home care. However, providing care to frail elders requires a large time commitment that may interfere with the caregiver's ability to work. Our goal was to determine the patient and caregiver characteristics associated with the reduction of employment hours in caregivers of frail elders. Methods. This was a cross-sectional study of 2806 patients (mean age 78, 73% women, 29% African American, 12% Hispanic, 54% with dementia) with at least one potentially working caregiver (defined as one who is either currently employed or who would have been employed if they had not been providing care) and their 4592 potentially working caregivers. Patients were enrollees at I I sites of the Program of All-Inclusive Care for the Elderly (PACE). Social workers interviewed patients and caregivers at the time of PACE enrollment. Caregivers were asked if they had reduced the hours they worked or had stopped working to care for the patient. Nurses interviewed patients and caregivers to assess independence in activities of daily living (ADLs) and the presence of behavioral disturbances. Comorbid conditions were assessed by physicians during enrollment examinations. Results. A total of 604 (22%) of the 2806 patients had at least one caregiver who either reduced the number of hours they worked or quit working to care for the patient. Patient characteristics independently associated with a caregiver reducing hours or quitting work were ethnicity (odds ratio [OR] = 1.42, 95% confidence interval [CI] 1.14-1.78 for African American; OR = 1.90, 95% CI 1.43-2.52 for Hispanic), ADL function below the median (OR = 1.76,95% CI 1.44-2.15), a diagnosis of dementia (OR = 1.68, 95% CI = 1.31-2.17 if associated with a behavioral disturbance; OR = 1.31, 95% CI 1.06-1.63 if not associated with a behavioral disturbance), or a history of stroke (OR = 1.42, 95% CI 1.16-1.73). After controlling for these patient characteristics, caregiver characteristics associated with reducing work hours included being the daughter or daughter-in-law of the patient (OR = 1.69, 95% CI 1.37-2.08) and living with the patient (OR = 4.66, 95% CI 3.65-5.95 if no other caregiver lived at home, OR = 2.53, 95% CI 2.03-3.14 if another caregiver lived at home). Conclusions. Many caregivers reduce the number of hours they work to care for frail elderly relatives. The burden of reduced employment is more likely to be incurred by the families of ethnic minorities and of patients with specific clinical characteristics. Daughters and caregivers who Eve with the patient are more likely to reduce work hours than other caregivers. Future research should examine the impact of lost caregiver employment on patients' families and the ways in which the societal responsibility of caring for frail elders can be equitably shared. C1 San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. On Lok Senior Hlth Serv, San Francisco, CA USA. Case Western Reserve Univ, Metrohlth Med Ctr, Div Nephrol, Cleveland, OH 44106 USA. Univ S Carolina, Sch Med, Div Geriatr, Columbia, SC 29208 USA. Palmetto Hlth Alliance, Columbia, SC USA. RP Covinsky, KE (reprint author), San Francisco VA Med Ctr, Div Geriatr, 111G,4150 Clement St,Bldg 1, San Francisco, CA 94121 USA. RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU PHS HHS [K02H500006-01] NR 31 TC 52 Z9 54 U1 6 U2 16 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 NOV PY 2001 VL 56 IS 11 BP M707 EP M713 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 489LG UT WOS:000171992400014 PM 11682579 ER PT J AU Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Gingerich, R Egan, JM Elahi, D AF Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Gingerich, R Egan, JM Elahi, D TI Glucagon-like peptide-1 (7-37) augments insulin-mediated glucose uptake in elderly patients with diabetes SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID RAT SKELETAL-MUSCLE; GLYCOGEN-SYNTHASE; GLP-I; MELLITUS; HORMONE; AMIDE; GLP-1(7-36)AMIDE; HEPATOCYTES; METABOLISM; ADIPOCYTES AB Background. Glucagon-Like peptide-1 (GLP-1) is an intestinal insulinotropic hormone that augments glucose-induced insulin secretion in patients with type 2 diabetes. It has also been proposed that a substantial component of the glucose-lowering effects of GLP-1 occurs because this hormone enhances insulin-mediated glucose disposal. However, interpretations of the studies have been controversial. This study determines the effect of GLP-1 on insulin-mediated glucose disposal in elderly patients with type 2 diabetes. Methods. Studies were conducted on 8 elderly patients with type 2 diabetes (age range, 76 +/- 1 years; body mass index, 28 +/- 1 kg/m(2)). Each subject underwent two 180-minute euglycemic (insulin infusion rate, 40 mU/m(2)/min) insulin clamps in random order. Glucose production (Ra) and disposal (Rd) rates were measured using tritiated. glucose methodology. In one study, glucose and insulin alone were infused. In the other study, a primed-continuous infusion of GLP-1 was administered at a final rate of 1.5 pmol . ka(-1) . min(-1) from 30 to 180 minutes. Results. Glucose values were similar between the control and GLP-1 infusion studies. 120- to 180-minute insulin values appeared to be higher during the GLP-1 infusion study (control, 795 +/- 63 pmol/l; GLP-1, 1140 +/- 275 pmol/l; p = not significant [NS]). The higher insulin values were largely due to 2 subjects who had substantial insulin responses to GLP-1 despite euglycemia and hyperinsulinemia. The 120- to 180-minute insulin values were similar in the other 6 subjects (Control, 746 +/- 35 pmol/l; GLP-1, 781 +/- 41 pmol/l; p = NS). Basal (control, 2.08 +/- 0.05 mg/kg/min; GLP-1, 2.13 +/- 0.04 mg/kg/min; p = NS) and 120- to 180-minute (control, 0.50 +/- 0.18 mg/kg/min; GLP-1, 0.45 +/- 0.14 mg/kg/min; p = NS) Ra was similar between studies. The 120- to 180-minute Rd values were higher during the GLP-1 infusion studies (control. 4.73 +/- 0.39 mg/kg/min; GLP-1, 5.52 +/- 0.43 mg/kg/min; p < 0.1). When the 2 subjects who had significant insulin responses to GLP-1 during the euglycemic clamp were excluded, the 120- to 180-minute Rd values were still higher in the GLP-1 infusion study (control, 5.22 +/- 0.32 mg/kg/min; GLP-1, 6.05 +/- 037 mg/kg/min; p < .05). Conclusions. We conclude that GLP-1 may enhance insulin sensitivity in elderly patients with diabetes. C1 Univ British Columbia, Dept Med, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Physiol, Vancouver, BC V5Z 1M9, Canada. Harvard Univ, Sch Med, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02115 USA. Linco Res, St Charles, MO USA. NIA, Lab Clin Physiol, Gerontol Res Ctr, NIH, Baltimore, MD USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Meneilly, GS (reprint author), Vancouver Hosp & Hlth Sci Ctr, Room S169,UBC Site,2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. NR 26 TC 20 Z9 20 U1 0 U2 1 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 NOV PY 2001 VL 56 IS 11 BP M681 EP M685 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 489LG UT WOS:000171992400010 PM 11682575 ER PT J AU Brady, CB Spiro, A McGlinchey-Berroth, R Milberg, W Gaziano, JM AF Brady, CB Spiro, A McGlinchey-Berroth, R Milberg, W Gaziano, JM TI Stroke risk predicts verbal fluency decline in healthy older men: Evidence from the normative aging study SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID COGNITIVE PERFORMANCE; VASCULAR DEMENTIA; FRONTAL-LOBE; ALZHEIMERS-DISEASE; DYSFUNCTION; LESIONS; MEMORY AB Risk factors for stroke cause ischemic changes in the cerebral white matter that may affect frontal lobe functions more than other brain functions. Therefore, stroke risk could specifically affect performance on behavioral indexes traditionally associated with frontal lobe function such as verbal fluency. The authors examined this hypothesis in 235 healthy older men (mean age = 66.41 years) who received concurrent medical and neuropsychological examinations twice at a 3-year interval. Relations between stroke risk and decline in verbal fluency, memory, and visuospatial performance were analyzed through regression, controlling for age and education. Age was associated with decline in all cognitive functions; stroke risk was associated with decline only on verbal fluency. The relation between stroke risk and fluency decline was 80% as large as that between age and fluency decline. These results suggest that stroke risk rivals the effects of aging on verbal fluency performance. C1 VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr 182, Boston, MA 02130 USA. VA Boston Healthcare Syst, Normat Aging Study, Boston, MA 02130 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. Harvard Univ, Dept Psychiat, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. RP Brady, CB (reprint author), VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr 182, 150 S Huntington Ave, Boston, MA 02130 USA. RI McGlinchey, Regina/R-1971-2016 FU NIA NIH HHS [AG13000]; NIAAA NIH HHS [AA08941]; NINDS NIH HHS [5R01NS29342-05] NR 42 TC 28 Z9 28 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD NOV PY 2001 VL 56 IS 6 BP P340 EP P346 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 489MR UT WOS:000171995600003 PM 11682587 ER PT J AU Rosen, HR AF Rosen, HR TI Hepatitis B and C in the liver transplant recipient: Current understanding and treatment SO LIVER TRANSPLANTATION LA English DT Article; Proceedings Paper CT Meeting of the American-Association-for-the-Study-of-Liver-Diseases/International-Liver -Transplantation-Society CY NOV 09, 2001 CL DALLAS, TEXAS SP Amer Assoc Stud Liver Dis, Internat Liver Transplant Soc ID IMMUNE GLOBULIN; LAMIVUDINE THERAPY; GRAFT REINFECTION; INFECTED PATIENTS; INTERFERON-ALPHA; VIRUS RECURRENCE; SURFACE-ANTIGEN; UNITED-STATES; FOLLOW-UP; PROPHYLAXIS AB 1. Liver disease related to chronic viral hepatitis is the leading indication for orthotopic liver transplantation (OLT) worldwide. 2. The natural history of hepatitis B virus infection has been dramatically modified, and outcome has improved substantially in the last decade with the use of hepatitis B immunoglobulin and lamivudine. 3. Hepatitis C virus (HCV) recurrence, defined by histological injury, is almost universal, and a subset of patients (20% to 30%) develops allograft cirrhosis by the fifth year post-OLT. 4. Unfortunately, antiviral therapy for hepatitis C post-OLT, even when initiated preemptively before the development of histological recurrence in the first few weeks post-OLT, has failed to alter the natural history of HCV disease recurrence. 5. HCV-related allograft cirrhosis is associated with a high rate of decompensation and mortality. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. Portland Vet Adm, Liver Transplantat Program, Portland, OR USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Div Gastroenterol Hepatol, POB 1034,P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. NR 75 TC 16 Z9 16 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 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2001 VL 7 IS 11 SU 1 BP S87 EP S98 DI 10.1053/jlts.2001.28519 PG 12 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 492JU UT WOS:000172165300012 PM 11689781 ER PT J AU Clark, JI Kancharla, K Qamar, R Fisher, S Hantel, A Panganiban, J Millbrandt, L Albain, KS AF Clark, JI Kancharla, K Qamar, R Fisher, S Hantel, A Panganiban, J Millbrandt, L Albain, KS TI Pilot study of sequential vinorelbine and cisplatin followed by docetaxel for selected IIIB and stage IV non-small cell lung cancer SO LUNG CANCER LA English DT Article DE sequential therapy; pilot study; non-small cell lung cancer ID SOUTHWEST-ONCOLOGY-GROUP; RANDOMIZED TRIAL; CHEMOTHERAPY; IFOSFAMIDE; SURVIVAL; P53 AB Vinorelbine, cisplatin and docetaxel are known to be efficacious in non-small cell lung cancer (NSCLC). This limited institution pilot study evaluated the novel strategy of sequencing active first line agents prior to progression. The primary objective of this study was to assess the toxicity profile in anticipation of a larger cooperative group standard phase If study. Patients with selected stage IIIB and IV NSCLC, Southwest Oncology Group (SWOG) performance status (PS) of I or less and measurable or evaluable disease were eligible. Treatment was cisplatin 100 mg/ml(2) day I and 29, vinorelbine 25 mg/m(2) weekly for 8 weeks, followed by docetaxel 100 mg/m(2) every 21 days for four cycles if no progression. If grade IV neutropenia developed, G-CSF 5 mcg/kg/day was used in subsequent cycles. Of IS eligible patients, 17 patients had stage IV disease with a median age of 66 years (range 48-80). Eight patients had a SWOG PS of 1, 10 had a PS of zero. Six of eighteen patients received all 8 weeks of vinorelbine/cisplatin and six of eight patients who went on to receive docetaxel received all four planned cycles; only two patients overall received all planned therapy. One grade III/IV event each of cardiotoxicity myocardial infarction), renal toxicity (acute renal failure), anemia and thrombocytopenia occurred with vinorelbine and cisplatin, and 2 Grade IV hypersensitivity reactions, manifested by severe back pain with docetaxel occurred. Three deaths occurred during the study, all during treatment with vinorelbine and cisplatin: one due to neutropenic sepsis, one from a pulmonary embolism; and one secondary to severe hypoglycemia in a diabetic patient. Of the 16 patients evaluable for response after vinorelbine/cisplatin, there were two complete responses (12.5%) and three partial responses (19%) for an overall response rate of 31% (95% CI 8 - 58). One additional patient who received docetaxel experienced a partial response. Two patients remain alive (21 + and 18 + months, respectively). The 1-year survival was 44%. Conclusion: This sequence, as defined, was tolerated marginally well in patients with advanced NSCLC. Granulocytopenia was the major toxicity requiring dose adjustments throughout the sequence. Based on response rates and tolerability that were somewhat comparable to other regimens in this disease setting, a modified version of this program, adjusted to decrease the incidence of grade III and IV toxicity, was selected as one arm of a recent randomized phase II trial in the Southwest Oncology Group (SWOG), S9806, evaluating sequential therapy in advanced NSCLC. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Edward Hosp, Naperville, IL USA. RP Clark, JI (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. RI qamar, raheel/D-4543-2012 NR 23 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD NOV PY 2001 VL 34 IS 2 BP 271 EP 277 DI 10.1016/S0169-5002(01)00251-3 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 498KP UT WOS:000172509000013 PM 11679186 ER PT J AU Karakousis, PC Page, KR Varello, MA Howlett, PJ Stieritz, DD AF Karakousis, PC Page, KR Varello, MA Howlett, PJ Stieritz, DD TI Waterhouse-Friderichsen syndrome after infection with group A streptococcus SO MAYO CLINIC PROCEEDINGS LA English DT Article ID SPLENECTOMY; BACTEREMIA; PATIENT; DISEASE AB We report a case of Waterhouse-Friderichsen syndrome associated with group A streptococcus (GAS) toxic shock syndrome in a previously healthy man. The patient presented with neck pain and fevers of 2 days' duration. Computed tomography of the neck revealed a mass in the retropharyngeal space, suggesting an abscess. Despite prompt treatment with appropriate antibiotics, the patient experienced a fulminant course and died within 8 hours of presentation. Antemortem blood cultures grew GAS positive for exotoxins A, B, and C. Postmortem examination revealed bilateral adrenal hemorrhage, consistent with Waterhouse-Friderichsen syndrome. Immunohistochemical analysis of the adrenal glands revealed the presence of GAS antigens. However, no disseminated intravascular coagulation was evident. This case demonstrates that adrenal hemorrhage can occur without associated coagulopathy and may result directly from the action of bacterial toxins. C1 Hosp Univ Penn, Dept Internal Med, Philadelphia, PA 19104 USA. Philadephia Vet Affairs Med Ctr, Dept Pathol, Philadelphia, PA USA. RP Karakousis, PC (reprint author), 1823 Pine St 2, Philadelphia, PA 19103 USA. NR 18 TC 14 Z9 15 U1 0 U2 0 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD NOV PY 2001 VL 76 IS 11 BP 1167 EP 1170 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 488WN UT WOS:000171960000014 PM 11702906 ER PT J AU Rhew, DC Weingarten, SR AF Rhew, DC Weingarten, SR TI Achieving a safe and early discharge for patients with community-acquired pneumonia SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID RESPIRATORY-TRACT INFECTIONS; SEQUENTIAL ANTIMICROBIAL THERAPY; IN-HOSPITAL OBSERVATION; LOW-RISK PATIENTS; EARLY SWITCH; INTRAVENOUS ANTIBIOTICS; CEFUROXIME AXETIL; ORAL ANTIBIOTICS; ECONOMIC-IMPACT; INTERVENTIONAL TRIAL AB Methods to achieve a safe and early discharge for patients with community-acquired pneumonia may include. early switch from parenteral to oral antibiotics and early discharge once a patient achieves clinical stability (e.g., systolic blood pressure 90 mm Hg or more, heart rate 100 beats per minute or less, respiratory rate 24 breaths per minute or fewer, temperature 38.3 degreesC [101 degreesF] or lower, oxygen saturation 90% or more, able to eat, and stable mental status) or fulfills appropriate criteria. For many patients, this may occur on day three of hospitalization. Elimination of in-hospital observation for patients who do not have an obvious reason for continued hospitalization is another method. Improved efficiency of care by implementing critical pathways, identifying and correcting causes of medically unnecessary hospital days, initiating early discharge planning, enlisting the services of a discharge coordinator, and organizing outpatient parenteral antibiotic treatment programs are also methods that can be used. These strategies are effective in many but not in all patients, and their application should be tempered with careful clinical judgment. C1 Zynx Hlth Inc, Beverly Hills, CA 90212 USA. Univ Calif Los Angeles, Sch Med, Greater Los Angeles Vet Affairs Healthcare Syst, Div Infect Dis,Dept Med, Los Angeles, CA 90024 USA. RP Rhew, DC (reprint author), Zynx Hlth Inc, 9100 Wilshire Blvd,Suite 655,East Tower, Beverly Hills, CA 90212 USA. NR 76 TC 9 Z9 9 U1 2 U2 3 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 NOV PY 2001 VL 85 IS 6 BP 1427 EP + DI 10.1016/S0025-7125(05)70389-8 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA 483DA UT WOS:000171617400008 PM 11686189 ER PT J AU Zygmanski, P Kung, JH AF Zygmanski, P Kung, JH TI Method of identifying dynamic multileaf collimator irradiation that is highly sensitive to a systematic MLC calibration error SO MEDICAL PHYSICS LA English DT Article DE intensity modulated radiotherapy; multileaf collimator; quality assurance ID INTENSITY-MODULATED RADIOTHERAPY; QUALITY ASSURANCE; CONFORMAL RADIOTHERAPY; GENERATION; DOSIMETRY AB In intensity modulated radiotherapy (IMRT), radiation is delivered in a multiple of multileaf collimator (MLC) subfields. A subfield with a small leaf-to-leaf opening is highly sensitive to a leaf-positional error. We introduce a method of identifying and rejecting IMRT plans that are highly sensitive to a systematic MLC gap error (sensitivity to possible random leaf-positional errors is not addressed here). There are two sources of a systematic MLC gap error: centerline mechanical offset (CMO) and, in the case of a rounded end MLC, radiation field offset (RFO). In IMRT planning system, using an incorrect value of RFO introduces a systematic error Delta RFO that results in all leaf-to-leaf gaps that are either too large or too small by (2 . Delta RFO), whereas assuming that CMO is zero introduces systematic error Delta CMO that results in all gaps that are too large by Delta CMO=CMO. We introduce a concept of the average leaf pair Opening (ALPO) that can be calculated from a dynamic MLC delivery file. We derive an analytic formula for a fractional average fluence error resulting from a systematic gap error of Ax and show that it is inversely proportional to ALPO; explicitly it is equal to Deltax/(ALPO+ 2 . RFO + epsilon), in which epsilon is generally of the order of 1 mm and Deltax = 2 . Delta RFO + CMO. This analytic relationship is verified with independent numerical calculations. (C) 2001 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Zygmanski, P (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 16 TC 20 Z9 20 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2001 VL 28 IS 11 BP 2220 EP 2226 DI 10.1118/1.1408284 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 496KY UT WOS:000172395800005 PM 11764025 ER PT J AU Orban, T Landaker, E Ruan, Z Cordeman, TP Weitgasser, R Bonner-Weir, S Jackson, RA Patti, ME AF Orban, T Landaker, E Ruan, Z Cordeman, TP Weitgasser, R Bonner-Weir, S Jackson, RA Patti, ME TI High-fructose diet preserves beta-cell mass and prevents diabetes in nonobese diabetic mice: A potential role for increased insulin receptor substrate-2 expression SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID ANTIGEN EXPRESSION; FUNCTIONAL-STATE; RAT; SENSITIVITY; METABOLISM; MELLITUS; GLUCOSE; OBESE; SUPPLEMENTATION; TRANSPLANTATION AB We demonstrate that a high-fructose diet reduces the incidence of diabetes in nonobese diabetic (NOD) mice (31.2% v 57.1% on regular chow (RC); P =.009). In a second cohort of mice, we evaluated potential mechanisms for the protective effect of the high-fructose (HF) diet and whether the metabolic changes are strain-specific. Sixty NOD and 60 Balb/c mice were randomized at weaning into HF- and RC-fed groups (30 mice each) and followed for 28 weeks. Glucose tolerance testing demonstrated improved glucose tolerance in HF diet groups (P =.001 in Balb/c, P =.04 in NOD mice at 6 months). beta -cell mass was preserved in NOD mice on the HF diet, but remained unchanged in Balb/c mice. In NOD mice, hepatic insulin receptor substrate (IRS)-2 protein expression increased by 2-fold (P =.01 for 2 v 6 months) in HF-fed mice and was 53% +/- 15% higher (P =.01) in the HF diet versus RC groups at 6 months of age. IRS-2 expression was also increased in skeletal muscle of NOD mice and in both liver and muscle of Balb/c mice. Our data suggest that a HF diet improves glucose tolerance in both NOD and Balb/c mice. The improved glucose tolerance may be related to increased IRS-2 expression and, in NOD mice, preservation of beta -cell mass. Copyright (C) 2001 by W.B. Saunders Company. C1 Joslin Diabet Ctr, Immunol Sect, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. Joslin Diabet Ctr, Sect Islet Transplantat & Cellular Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Orban, T (reprint author), Joslin Diabet Ctr, Immunol Sect, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 02526-03] NR 41 TC 7 Z9 8 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 2001 VL 50 IS 11 BP 1369 EP 1376 DI 10.1053/meta.2001.27191 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 490XE UT WOS:000172078300019 PM 11699059 ER PT J AU Eischen, CM Roussel, MF Korsmeyer, SJ Cleveland, JL AF Eischen, CM Roussel, MF Korsmeyer, SJ Cleveland, JL TI Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE ARREST; TUMOR-SUPPRESSOR P53; BCL-2 FAMILY-MEMBERS; C-MYC; HEMATOPOIETIC MALIGNANCIES; TRANSGENIC MICE; P53-DEPENDENT APOPTOSIS; FRAMESHIFT MUTATIONS; GENE-EXPRESSION; DEFICIENT MICE AB The ARF and p53 tumor suppressors mediate Myc-induced apoptosis and suppress lymphoma development in E mu -myc transgenic mice. Here we report that the proapoptotic Bcl-2 family member Bax also mediates apoptosis triggered by Myc and inhibits Myc-induced lymphomagenesis. Bax-deficient primary pre-B cells are resistant to the apoptotic effects of Myc, and Bax loss accelerates lymphoma development in E mu -myc transgenics in a dose-dependent fashion. Eighty percent of lymphomas arising in wild-type E mu -myc transgenics have alterations in the ARF-Mdm2-p53 tumor suppressor pathway characterized by deletions in ARF, mutations or deletions of p53, and overexpression of Mdm2. The absence of Bax did not alter the frequency of biallelic deletion of ARF in lymphomas arising in E mu -myc transgenic mice or the rate of tumorigenesis in ARF-null mice. Furthermore, Mdm2 was overexpressed at the same frequency in lymphomas irrespective of Bax status, suggesting that Bax resides in a pathway separate from ARF and Mdm2. Strikingly, lymphomas from Bax-null E mu -myc transgenics lacked p53 alterations, whereas 27% of the tumors in Bax(+/-) E mu -myc transgenic mice contained p53 mutations or deletions. Thus, the loss of Bax eliminates the selection of p53 mutations and deletions, but not ARF deletions or Mdm2 overexpression, during Myc-induced tumorigenesis, formally demonstrating that Myc-induced apoptotic signals through ARF/Mdm2 and p53 must bifurcate: p53 signals through Bax, whereas this is not necessarily the case for ARF and Mdm2. C1 St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Tumor Cell Biol, Memphis, TN 38105 USA. Univ Tennessee, Dept Mol Sci, Memphis, TN 38163 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Eischen, CM (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc, 986805 Nebraska Med Ctr, Omaha, NE 68198 USA. EM ceischen@unmc.edu FU NCI NIH HHS [CA56819, CA21765, CA71907, CA76379, CA81695, F32 CA081695, P01 CA071907, P30 CA021765, R01 CA076379]; NIDDK NIH HHS [DK44158, R01 DK044158] NR 63 TC 125 Z9 128 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2001 VL 21 IS 22 BP 7653 EP 7662 DI 10.1128/MCB.21.22.7653-7662.2001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 485CW UT WOS:000171736800012 PM 11604501 ER PT J AU Bertrand, E Brouillet, E Caille, I Bouillot, C Cole, GM Prochiantz, A Allinquant, B AF Bertrand, E Brouillet, E Caille, I Bouillot, C Cole, GM Prochiantz, A Allinquant, B TI A short cytoplasmic domain of the amyloid precursor protein induces apoptosis in vitro and in vivo SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID ALZHEIMERS-DISEASE; WILD-TYPE; DNA FRAGMENTATION; TRANSGENIC MICE; BETA-PEPTIDE; CELLS; BRAIN; DEGENERATION; NEURONS; SIGNAL AB The amyloid precursor protein presents several cleavage sites leading to the release of its entire C-terminal domain into the cytoplasm. During apoptosis, this C-terminal domain can be cleaved at amino acid 664 by caspases 3, 6, and 8 and can thus generate two peptides N- and C-terminal to amino acid 664 (C31). Recently, it was shown that the C31 induces apoptosis after transfection into N2A and 293 T cell lines. We have analyzed here, by internalization into neurons, the physiological consequences of the entire C-terminal domain (APP-Cter) and of its membrane proximal sequence corresponding to the N-terminal peptide unmasked after caspase cleavage. We find that whereas micromolar concentrations of APP-Cter are harmless, the peptide extending from the membrane (amino acid 649) to the caspase cleavage site (amino acid 664) in the same range of concentrations induces DNA fragmentation, cleavage of actin at a caspase-sensitive site, and activates caspase 3. A mutated version of this sequence (tyrosine 653 replaced by an aspartate) abolishes the effect in vitro and in vivo. Taken together, this report suggests the existence of a new mechanism contributing to Alzheimer's Disease-associated cell death. C1 Ecole Normale Super, CNRS, UMR 8542, F-75230 Paris 05, France. VA Greater LA, GRECC 11E, Sepulveda, CA 91343 USA. RP Bertrand, E (reprint author), Ecole Normale Super, CNRS, UMR 8542, 46 Rue Ulm, F-75230 Paris 05, France. RI Brouillet, Emmanuel/B-4784-2014 OI Brouillet, Emmanuel/0000-0001-6322-7403 FU NIA NIH HHS [AG13471] NR 37 TC 55 Z9 58 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD NOV PY 2001 VL 18 IS 5 BP 503 EP 511 DI 10.1006/mcne.2001.1030 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 498QN UT WOS:000172522100005 PM 11922141 ER PT J AU D'Andrea, AD Garcia-Higuera, I Lane, WS Xu, B Kastan, MB Taniguchi, T AF D'Andrea, AD Garcia-Higuera, I Lane, WS Xu, B Kastan, MB Taniguchi, T TI Differential activation of the Fanconi Anemia protein, FANCD2, by monoubiquitination and phosphorylation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Harvard Microchem & Proteom Anal Facil, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 27 BP 5A EP 6A PG 2 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372500028 ER PT J AU Thomas, SM Chen, GC Turano, B Hagel, M Settleman, J AF Thomas, SM Chen, GC Turano, B Hagel, M Settleman, J TI Genetic interactions between the cytoskeletal adaptor, paxillin, and Rho family GTPases SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 22 BP 5A EP 5A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372500023 ER PT J AU Egelhoff, TT Steimle, PA Yumura, S Cote, CP Medley, QG Leppert, B AF Egelhoff, TT Steimle, PA Yumura, S Cote, CP Medley, QG Leppert, B TI Recruitment of myosin heavy chain kinase activity to actin-rich cortical structures SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Case Western Reserve Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. Univ N Carolina, Greensboro, NC 27412 USA. Yamaguchi Univ, Dept Biol, Yamaguchi, Japan. Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 200 BP 36A EP 36A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372500201 ER PT J AU Ku, NO Darling, J Wright, TL Krams, S Omary, MB AF Ku, NO Darling, J Wright, TL Krams, S Omary, MB TI Keratin 8 and 18 mutations associate with a broad range of human liver diseases SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Palo Alto VA Med Ctr, Dept Med, Palo Alto, CA 94304 USA. Stanford Univ, Palo Alto, CA 94304 USA. San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. Stanford Univ, Med Ctr, Dept Surg, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 303 BP 56A EP 56A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372500304 ER PT J AU Toivola, DM Ku, NO Nelson, DR Wright, TL Omary, MB AF Toivola, DM Ku, NO Nelson, DR Wright, TL Omary, MB TI Keratin hyperphosphorylation as a marker of human liver disease SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Palo Alto VA Med Ctr, Dept Med, Palo Alto, CA 94304 USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Florida, Coll Med, Gainesville, FL USA. San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 304 BP 56A EP 56A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372500305 ER PT J AU Gotte, M Joussen, AM Klein, C Andre, P Wagner, DD Hinkes, MT Adamis, AP Bernfield, M AF Gotte, M Joussen, AM Klein, C Andre, P Wagner, DD Hinkes, MT Adamis, AP Bernfield, M TI Lack of Syndecan-1 promotes leukocyte-endothelial interactions SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Hosp Munster, D-48149 Munster, Germany. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, 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 AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 332 BP 61A EP 61A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372500333 ER PT J AU Singh, IS Calderwood, S He, JR Hasday, JD AF Singh, IS Calderwood, S He, JR Hasday, JD TI A high affinity HSF-1 binding site in the 5 '-untranslated region of the marine Tumor Necrosis Factor-alpha gene is a transcriptional repressor SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 600 BP 110A EP 110A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372500600 ER PT J AU Bearer, EL Satpute, PS Schlief, ML Breakefield, XO Schuback, D Reese, TS AF Bearer, EL Satpute, PS Schlief, ML Breakefield, XO Schuback, D Reese, TS TI Direct video observation of anterograde transport of human herpes simplex virus in the giant axon of the squid: A model for anterograde axonal transport SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Brown Univ, Dept Pathol & Med, Providence, RI 02912 USA. Brown Univ, Providence, RI 02912 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Anat, St Louis, MO USA. Washington Univ, Sch Med, Neurobiol Ctr Study Nervous Syst Injury, St Louis, MO USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 900 BP 166A EP 166A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372500900 ER PT J AU Yang, XW Claas, C Kraeft, SK Chen, LB Hemler, ME AF Yang, XW Claas, C Kraeft, SK Chen, LB Hemler, ME TI Palmitoylation supports tetraspanin protein associations SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, 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 AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 1112 BP 205A EP 205A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372501112 ER PT J AU Francis, SA McCarthy, KM McCormack, JM Lynch, RD Schneeberger, EE AF Francis, SA McCarthy, KM McCormack, JM Lynch, RD Schneeberger, EE TI Depletion of membrane cholesterol (CH) alters detergent solubility, phosphorylation and susceptibility to proteolysis of tight junction (TJ) proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Lowell, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 1183 BP 217A EP 217A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372501183 ER PT J AU Lu, J Pazin, M Ravid, K AF Lu, J Pazin, M Ravid, K TI Properties of Ets-1 binding to chromatin: Its role in megakaryocyte gene expression SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Massachusetts Gen Hosp, CBRC, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 1223 BP 224A EP 224A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372501223 ER PT J AU Burton, K Wang, XY AF Burton, K Wang, XY TI A rapid light microscopic method for quantifying the positions of cells in 3D matrices SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2001 VL 12 SU S MA 1423 BP 260A EP 260A PG 1 WC Cell Biology SC Cell Biology GA 496AL UT WOS:000172372501420 ER EF