FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Paster, BJ Boches, SK Galvin, JL Ericson, RE Lau, CN Levanos, VA Sahasrabudhe, A Dewhirst, FE AF Paster, BJ Boches, SK Galvin, JL Ericson, RE Lau, CN Levanos, VA Sahasrabudhe, A Dewhirst, FE TI Bacterial diversity in human subgingival plaque SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DENTOALVEOLAR ABSCESSES; PERIODONTAL-DISEASE; SEQUENCE-ANALYSIS; PCR; MICROORGANISMS; IDENTIFICATION; ENDOCARDITIS; ENVIRONMENT; INFECTIONS; CREVICE AB The purpose of this study was to determine the bacterial diversity in the human subgingival plaque by using culture-independent molecular methods as part of an ongoing effort to obtain full 16S rRNA sequences for all cultivable and not-yet-cultivated species of human oral bacteria. Subgingival plaque was analyzed from healthy subjects and subjects with refractory periodontitis, adult periodontitis, human immunodeficiency virus periodontitis, and acute necrotizing ulcerative gingivitis. 16S ribosomal DNA (rDNA) bacterial genes from DNA isolated from subgingival plaque samples were PCR amplified with all-bacterial or selective primers and cloned into Escherichia coli. The sequences of cloned 16S rDNA inserts were used to determine species identity or closest relatives by comparison with sequences of known species. A total of 2,522 clones were analyzed. Nearly complete sequences of approximately 1,500 bases were obtained for putative new species. About 60% of the clones fell into 132 known species, 70 of which were identified from multiple subjects. About 40% of the clones were novel phylotypes. Of the 215 novel phylotypes, 75 were identified from multiple subjects. Known putative periodontal pathogens such as Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola were identified from multiple subjects, but typically as a minor component of the plaque as seen in cultivable studies. Several phylotypes fell into two recently described phyla previously associated with extreme natural environments, for which there are no cultivable species. A number of species or phylotypes were found only in subjects with disease, and a few were found only in healthy subjects. The organisms identified only from diseased sites deserve further study as potential pathogens. Based on the sequence data in this study, the predominant subgingival microbial community consisted of 347 species or phylotypes that fall into 9 bacterial phyla. Based on the 347 species seen in our sample of 2,522 clones, we estimate that there are 68 additional unseen species, for a total estimate of 415 species in the subgingival plaque. When organisms found on other oral surfaces such as the cheek, tongue, and teeth are added to this number, the best estimate of the total species diversity in the oral cavity is approximately 500 species, as previously proposed. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Biol, Boston, MA 02115 USA. RP Paster, BJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [R01 DE011443, DE-10374, DE-11443, R01 DE010374] NR 53 TC 1004 Z9 1079 U1 10 U2 95 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 2001 VL 183 IS 12 BP 3770 EP 3783 DI 10.1128/JB.183.12.3770-3783.2001 PG 14 WC Microbiology SC Microbiology GA 437KG UT WOS:000168990400027 PM 11371542 ER PT J AU Dong, Z Venkatachalam, MA Wang, JZ Patel, Y Saikumar, P Semenza, GL Force, T Nishiyama, J AF Dong, Z Venkatachalam, MA Wang, JZ Patel, Y Saikumar, P Semenza, GL Force, T Nishiyama, J TI Up-regulation of apoptosis inhibitory protein IAP-2 by hypoxia - HIF-1-independent mechanisms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCIBLE FACTOR 1-ALPHA; OXYGEN-SENSING PATHWAY; CYTOCHROME-C RELEASE; CELL-DEATH; CASPASE ACTIVATION; PUTATIVE MEMBERS; GENE-EXPRESSION; ERYTHROPOIETIN; COMPLEX; CANCER AB Hypoxia is a key determinant of tissue pathology during tumor development and organ ischemia. However, little is known regarding hypoxic regulation of genes that are directly involved in cell death or death resistance. Here we report the striking induction by severe hypoxia of the anti-apoptotic protein IAP-2. Hypoxic cells with IAP-2 up-regulation became resistant to apoptosis. IAP-2 was induced by hypoxia per se rather than by the secondary effects of hypoxia, including ATP depletion and cell injury. The inductive response did not relate to alterations of cellular redox status or arrest of mitochondrial respiration. On the other hand, IAP-2 induction was attenuated by actinomycin D, suggesting a role for gene transcription. In vitro nuclear run-on assays demonstrated specific increases in IAP-2 transcriptional activity after hypoxia exposure. HIF-1, the primary transcription factor that is responsible for multiple gene activation under hypoxia, does not have a role in IAP-2 expression. HIF-1 and IAP-2 were induced by different degrees of hypoxia; severe hypoxia or anoxia was required for IAP-2 induction. Moreover, cobalt chloride and desferrioxamine activated HIF-1 but not IAP-2. Finally, IAP-2 was induced by severe hypoxia in mouse embryonic stem cells that were deficient of HIF-1. Thus, this study not only provides the first demonstration of hypoxic regulation of an anti-apoptotic gene but also suggests the participation of novel hypoxia-responsive transcription mechanisms. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21287 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charleston, MA 02129 USA. RP Dong, Z (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [R01 DK054472, R01 DK054472-02] NR 59 TC 110 Z9 118 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 JUN 1 PY 2001 VL 276 IS 22 BP 18702 EP 18709 DI 10.1074/jbc.M011774200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000009 PM 11278985 ER PT J AU Yang, HL Reinherz, EL AF Yang, HL Reinherz, EL TI Dynamic recruitment of human CD2 into lipid rafts - Linkage to T cell signal transduction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYMPHOCYTE-T; CYTOPLASMIC DOMAIN; MEMBRANE DOMAINS; TYROSINE KINASE; ERYTHROPOIETIN RECEPTOR; BIOLOGICAL-MEMBRANES; ANTIGEN RECOGNITION; PLASMA-MEMBRANE; N-GLYCANS; ACTIVATION AB CD2 mediates T cell adhesion via its ectodomain and signal transduction utilizing its 117-amino acid cytoplasmic tail. Here we show that a significant fraction of human CD2 molecules is inducibly recruited into lipid rafts upon CD2 cross-linking by a specific pair of mitogenic anti-CD2 monoclonal antibodies (anti-T11(2), + anti-T11(3)) or during cellular conjugate formation by CD58, the physiologic ligand expressed on antigen-presenting cells. Translocation to lipid microdomains is independent of the T cell receptor (TCR) and, unlike inducible TCR-raft association, requires no tyrosine phosphorylation. Structural integrity of rafts is necessary for CDS stimulated elevation of intracellular free calcium and tyrosine phosphorylation of cellular substrates, Whereas murine CD2 contains two membrane-proximal intracellular cysteines, partitioning CD2 into cholesterol-rich lipid rafts constitutively, human CD2 has no cytoplasmic cysteines. Mapping studies using CD2 point mutation, deletion, and chimeric molecules suggest that conformational change in the CD2 ectodomain participates in inducible raft association and excludes the membrane-proximal N-linked glycans, the transmembrane segment, and the CD2 cytoplasmic region (residues 8-117) as necessary for translocation. Translocation of CD2 into lipid rafts may reorganize the membrane into an activation-ready state prior to TCR engagement by a peptide associated with a major histocompatibility complex molecule, accounting for synergistic T cell stimulation by CD2 and the TCR. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI21226] NR 80 TC 42 Z9 42 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 JUN 1 PY 2001 VL 276 IS 22 BP 18775 EP 18785 DI 10.1074/jbc.M009852200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000019 PM 11376005 ER PT J AU Choi, EK Zaidi, NF Miller, JS Crowley, AC Merriam, DE Lilliehook, C Buxbaum, JD Wasco, W AF Choi, EK Zaidi, NF Miller, JS Crowley, AC Merriam, DE Lilliehook, C Buxbaum, JD Wasco, W TI Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM-BINDING PROTEIN; NEURONAL CA2+ SENSOR-1; IN-VIVO; BETA-CATENIN; GUANYLATE-CYCLASE; NERVOUS-SYSTEM; CELLS; APOPTOSIS; ENDOPROTEOLYSIS; STAUROSPORINE AB Calsenilin is a member of the recoverin family of neuronal calcium-binding proteins that we have previously shown to interact with presenilin 1 (PS1) and presenilin 2 (PS2) holoproteins. The expression of calsenilin can regulate the levels of a proteolytic product of PS2 (Buxbaum, J. D., Choi, E, K., Luo, Y., Lilliehook, C., Crowley, A. C., Merriam, D. E., and Wasco, W. (1998) Not. Med. 4, 1177-1181) and reverse the presenilin-mediated enhancement of calcium signaling (Leissring, M. A., Yamasaki, T. R., Wasco, W., Buxbaum, J. I)., Parker, I., and LaFerla, F. M. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 8590-8593). Here, we have used cultured mammalian cells that transiently or stably express calsenilin to extend the characterization of calsenilin and of the calsenilin-PS2 interaction. We have found that calsenilin has the ability to interact with endogenous 25-kDa C-terminal fragment (CTF) that is a product of regulated endoproteolytic cleavage of PS2 and that the presence of the N141I PS2 mutation does not significantly alter the interaction of calsenilin with PS2. Interestingly, when the 25-kDa PS2 CTF and the 20-kDa PS2 CTF are both present, calsenilin preferentially interacts with the 20-kDa CTF. Increases in the 20-kDa fragment are associated with the presence of familial Alzheimer's disease-associated mutations (Kim, T., Pettingell, W, H., Jung, Y., Kovacs, D. M., and Tanzi, R. E. (1997) Science 277, 373-376). However, the finding that the production of the 20-kDa fragment is regulated by the phosphorylation of PS2 (Walter, J., Schindzielorz, A., Grunberg, J., and Haass, C, (1999) Proc. Natl. Acad Sci. U.S.A. 96, 1391-1396) suggests that it is a regulated physiological event that also occurs in the absence of the familial Alzheimer's disease-associated mutations in PS2. Finally, we have demonstrated that calsenilin is a substrate for caspase-3, and we have used site-directed mutagenesis to map the caspase-3 cleavage site to a region that is proximal to the calcium binding domain of calsenilin. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. Mt Sinai Sch Med, Dept Psychiat & Neurobiol, New York, NY 10029 USA. RP Wasco, W (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, 114 16th St, Charlestown, MA 02129 USA. OI Buxbaum, Joseph/0000-0001-8898-8313 FU NIA NIH HHS [AG05138, AG15801, AG16361]; NINDS NIH HHS [NS35975] NR 64 TC 58 Z9 62 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 JUN 1 PY 2001 VL 276 IS 22 BP 19197 EP 19204 DI 10.1074/jbc.M008597200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000076 PM 11278424 ER PT J AU Parks, WT Frank, DB Huff, C Haft, CR Martino, J Meng, XW de Caestecker, MP McNally, JG Reddi, A Taylor, SI Roberts, AB Wang, TW Lechleider, RJ AF Parks, WT Frank, DB Huff, C Haft, CR Martino, J Meng, XW de Caestecker, MP McNally, JG Reddi, A Taylor, SI Roberts, AB Wang, TW Lechleider, RJ TI Sorting nexin 6, a novel SNX, interacts with the transforming growth factor-beta family of receptor serine-threonine kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I RECEPTORS; SMAD PROTEINS; ACTIVIN; COMPLEX; ACTIVATION; MEMBRANE; CLONING; IDENTIFICATION; BIOSYNTHESIS; RESPONSES AB Sorting nexins (SNX) comprise a family of proteins with homology to several yeast proteins, including Vps5p and Mvp1p, that are required for the sorting of proteins to the yeast vacuole. Human SNX1, -2, and -4 have been proposed to play a role in receptor trafficking and have been shown to bind to several receptor tyrosine kinases, including receptors for epidermal growth factor, platelet-derived growth factor, and insulin as well as the long form of the leptin receptor, a glycoprotein 130-associated receptor. We now describe a novel member of this family, SNX6, which interacts with mem bers of the transforming growth factor-p family of receptor serine-threonine kinases. These receptors belong to two classes: type II receptors that bind ligand, and type I receptors that are subsequently recruited to transduce the signal. Of the type II receptors, SNX6 was found to interact strongly with ActRIIB and more moderately with wild type and kinase-defective mutants of T beta RII. Of the type I receptors, SNX6 was found to interact only with inactivated T beta RI. SNXs 1-4 also interacted with the transforming growth factor-p receptor family, showing different receptor preferences. Conversely, SNX6 behaved similarly to the other SNX proteins in its interactions with receptor tyrosine kinases. Strong heteromeric interactions were also seen among SNX1, -2, -4, and -6, suggesting the formation in vivo of oligomeric complexes. These findings are the first evidence for the association of the SNX family of molecules with receptor serine-threonine kinases. C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Surg, Boston, MA 02114 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. OI Parks, W. Tony/0000-0001-7341-3277 NR 36 TC 93 Z9 99 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 JUN 1 PY 2001 VL 276 IS 22 BP 19332 EP 19339 DI 10.1074/jbc.M100606200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000093 PM 11279102 ER PT J AU Herrera, C Morimoto, C Blanco, J Mallol, J Arenzana, F Lluis, C Franco, R AF Herrera, C Morimoto, C Blanco, J Mallol, J Arenzana, F Lluis, C Franco, R TI Comodulation of CXCR4 and CD26 in human lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CD26/DIPEPTIDYL PEPTIDASE-IV; HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL ACTIVATION; ADENOSINE-DEAMINASE; HIV-1 ENTRY; FACTOR 1-ALPHA; SURFACE; RECEPTOR; EXPRESSION; BINDING AB We provide convergent and multiple evidence for a CD26/CXCR4 interaction. Thus, CD26 codistributes with CXCR4, and both coimmunoprecipitate from membranes of T (CD4(+)) and B (CD4(-)) cell lines. Upon induction with stromal cell-derived factor 1 alpha (SDF-1 alpha), CD26 is cointernalized with CXCR4. CXCR4-mediated downregulation of CD26 is not induced by antagonists or human immunodeficiency virus (HIV)-1 gp120. SDF-1 alpha -mediated down-regulation of CD26 is not blocked by pertussis toxin but does not occur in cells expressing mutant CXCR4 receptors unable to internalize. Codistribution and cointernalization also occurs in peripheral blood lymphocytes. Since CD26 is a cell surface endopeptidase that has the capacity to cleave SDF-1 alpha, the CXCR4CD26 complex is likely a functional unit in which CD26 may directly modulate SDF-1 alpha -induced chemotaxis and antiviral capacity. CD26 anchors adenosine deaminase (ADA) to the lymphocyte cell surface, and this interaction is blocked by HIV-1 gp120. Here we demonstrate that gp120 interacts with CD26 and that gp120-mediated disruption of ADA/CD26 interaction is a consequence of a first interaction of gp120 with a domain different from the ADA binding site. SDF-1 alpha and gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 colocalize and in which ADA is not present. The physical association of CXCR4 and CD26, direct or part of a supramolecular structure, suggests a role on the function of the immune system and the pathophysiology of HIV infection. C1 Univ Barcelona, Dept Bioquim & Biol Mol, Fac Chem, E-08028 Barcelona, Spain. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Biol, Boston, MA 02115 USA. Natl Inst Infect Dis, Ctr AIDS Res, Tokyo 1620052, Japan. Inst Pasteur, Dept SIDA Retrovirus, F-75724 Paris, France. Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Inst Recerca SIDA IRSI Caixa Fdn, Badalona 08916, Spain. RP Franco, R (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, Fac Chem, Marti Franques 1, E-08028 Barcelona, Spain. RI Blanco, Julia/A-5347-2008; Franco, Rafael/C-3694-2015 OI Blanco, Julia/0000-0002-2225-0217; Franco, Rafael/0000-0003-2549-4919 NR 38 TC 64 Z9 65 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 JUN 1 PY 2001 VL 276 IS 22 BP 19532 EP 19539 DI 10.1074/jbc.M004586200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 439BM UT WOS:000169091000116 PM 11278278 ER PT J AU Weaver, DR Capodice, CE AF Weaver, DR Capodice, CE TI Postmortem stability of melatonin receptor binding and clock-relevant mRNAs in mouse suprachiasmatic nucleus SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE suprachiasmatic nucleus; clock genes; mRNA stability; receptor stability; melatonin; sleep ID VASOPRESSIN MESSENGER-RNA; RAT-BRAIN; SLEEP PROPENSITY; CIRCADIAN PACEMAKER; BIOLOGICAL CLOCK; EXPRESSION; TEMPERATURE; GENE; AGE; MECHANISMS AB The stability of receptor proteins and mRNAs in brain tissue is variable after death. As a prelude to quantitative studies of melatonin receptor density and clock gene expression in the human brain, the stability of these macromolecules was examined in the mouse brain under simulated postmortem conditions using the model of Spokes and Koch. In the mouse suprachiasmatic nucleus (SCN), melatonin receptor binding was significantly reduced after 18 to 24 h under postmortem conditions. Two mRNAs that are rhythmically expressed in the SCN, mPer1 and prepropressophysin (AVP), also decreased significantly over the interval studied, and mPer1 declined more rapidly than AVP. Both mPer1 and AVP mRNA levels in the SCN declined more rapidly in vivo than under postmortem conditions, suggesting that the degradation of these mRNAs is an active process. The results indicate that quantitative studies of melatonin receptor density on human postmortem material are feasible and that detection of rhythmic gene expression in the human SCN will likely require collection of specimens with a rather short (< 8 h) interval from death to tissue collection. The relative stability of melatonin receptor binding in the SCN also suggests that receptor binding may be a reliable marker for the location of the SCN in studies assessing clock gene expression in postmortem material. C1 Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. RP Weaver, DR (reprint author), Univ Massachusetts, Sch Med, Dept Neurobiol, 55 Lake Ave N, Worcester, MA 01655 USA. FU NIA NIH HHS [P01 AG 09975]; NINDS NIH HHS [R01 NS 39303] NR 45 TC 7 Z9 8 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD JUN PY 2001 VL 16 IS 3 BP 216 EP 223 DI 10.1177/074873001129001926 PG 8 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 482WH UT WOS:000171599900004 PM 11407781 ER PT J AU Deirmengian, CA Lee, SGP Jupiter, JB AF Deirmengian, CA Lee, SGP Jupiter, JB TI Neuropathic arthropathy of the elbow - A report of five cases SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID JOINT; DIAGNOSIS; DISEASE; BONE AB Background: Neuropathic arthropathy of the elbow is rare and characterized by a painless but unstable articulation. The functional capacity of patients with this condition has not been reviewed in detail. Methods: Five male patients, with an average age of fifty-one years, were treated for neuropathic arthropathy of the elbow. The underlying conditions associated with the arthropathy included syringomyelia, insulin-dependent diabetes mellitus, end-stage renal failure, and two cases of polyneuropathy of unknown cause. Four patients sought medical attention after a specific traumatic event. Peripheral sensory and motor dysfunction was present in each patient. Radiographs of the elbow revealed dislocation, fracture fragmentation, and heterotopic ossification. Our management of the neuropathic elbows centered on maintenance of a functional are of motion through physical therapy aimed at regaining muscle strength and the use of orthoses for support. Operative treatment was performed for an associated ulnar or radial nerve compression syndrome in three patients, and an open reduction and internal fixation of an unstable proximal ulnar nonunion associated with loose implants was performed in one. Results: The patients were followed for an average of nineteen months, with a range of twelve to thirty-six months. All patients had a pain-free elbow with a functional range of motion at the most recent follow-up examination, and none wished to have further treatment. The operatively treated ulnar nonunion united successfully. All three patients treated surgically for an associated nerve compression syndrome had recovery of nerve function. Conclusion: In the face of instability and gross distortion of the joint, the patients in this series demonstrated remarkably good function. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Deirmengian, CA (reprint author), Univ Penn, Sch Med, 3400 Spruce St, Philadelphia, PA 19104 USA. NR 27 TC 21 Z9 23 U1 0 U2 0 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 JUN PY 2001 VL 83A IS 6 BP 839 EP 844 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 440DF UT WOS:000169160100005 PM 11407791 ER PT J AU Deng, WJ Stashenko, P Chen, W Liang, YQ Shimizu, K Li, YP AF Deng, WJ Stashenko, P Chen, W Liang, YQ Shimizu, K Li, YP TI Characterization of mouse Atp6i gene, the gene promoter, and the gene expression SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 78th General Session of the International-and-American-Associations-for-Dental-Research CY APR 05-09, 2000 CL WASHINGTON, D.C. SP Int Assoc Dent Res, Amer Assoc Dent Res DE osteoclast gene; characterization of Atp6i gene promoter; gene expression pattern; gene organization ID MEDIATED EXTRACELLULAR ACIDIFICATION; VACUOLAR H+-ATPASE; OSTEOCLAST DIFFERENTIATION; MOLECULAR-CLONING; BONE-RESORPTION; GELATINASE-B; PROTON PUMP; 3 ISOFORMS; OSTEOPETROSIS; SUBUNIT AB Solubilization of bone mineral by osteoclasts depends on the formation of an acidic extracellular compartment through the action of a V-type ATPase, We previously cloned a gene encoding a putative osteoclast-specific proton pump subunit, termed OC-116 kDa, approved mouse Atp6i (ATPase, Ht transporting, [vacuolar proton pump] member I), The function of Atp6i as osteoclast-specific proton pump subunit was confirmed in our mouse knockout study.:However, the transcription regulation of Atp6i remains largely unknown. In this study, the gene encoding mouseiitp6i and the promoter have been isolated and completely sequenced. In addition, the temporal and spatial expressions of Atp6i have been characterized. Intrachromosomal mapping studies revealed that the gene contains 20 exons and 19 introns spanning similar to 11 kilobases (kb) of genomic DNA, Alignment of the mouse Atp6i gene exon sequence and predicted amino acid sequence to that of the human reveals a strong homology at both the nucleotide (82%) and the amino acid (80%) levels. Primer extension assay indicates that there is one transcription start site at 48 base pairs (bp) upstream of the initiator Met codon, Analysis of 4 kb of the putative promoter region indicates that this gene lacks canonical TATA and CAAT boxes and contains multiple putative transcription regulatory elements. Northern blot analysis of RNAs from a number of mouse tissues reveals that Atp6i is expressed predominantly in osteoclasts, and this predominant expression was confirmed by reverse-transcription polymerase chain reaction (RT-PCR) assay and immunohistochemical analysis. Whole-mount in situ hybridization shows that Atp6i- expression is detected initially in the headfold region and posterior region in the somite stage of mouse embryonic development (E8.5) and becomes progressively restricted to anterior regions and the limb bud by E9.5, The expression level of Atp6i is largely reduced after E10.5. This is the first report of the characterizations of Atp6i gene,its promoter, and its gene expression patterns during mouse development. This study may provide valuable insights into the function of Atp6i, its osteoclast-selective expression, regulation, and the molecular mechanisms responsible for osteoclast activation. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Forsyth Dept Oral Biol, Forsyth Dent Ctr, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Li, YP (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR44741]; NIDCR NIH HHS [DE-07378] NR 26 TC 13 Z9 13 U1 1 U2 1 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 JUN PY 2001 VL 16 IS 6 BP 1136 EP 1146 DI 10.1359/jbmr.2001.16.6.1136 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 433XX UT WOS:000168786900018 PM 11393791 ER PT J AU Maslow, AD Mashikian, J Haering, JM Heindel, S Douglas, P Levine, R AF Maslow, AD Mashikian, J Haering, JM Heindel, S Douglas, P Levine, R TI Transesophageal echocardiographic evaluation of native aortic valve area: Utility of the double-envelope technique SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE echocardiography; transesophageal; aortic valve; stenosis; double envelope; planimetry ID VENTRICULAR EJECTION FRACTION; CONTINUOUS-WAVE DOPPLER; ORIFICE AREA; CARDIAC-OUTPUT; PRESSURE RECOVERY; PROSTHETIC VALVE; GORLIN FORMULA; STENOSIS; MULTIPLANE; FLOW AB Objective: To assess the accuracy of aortic valve area (AVA) calculations using the continuity equation with data obtained from the double envelope (DE) (simultaneously obtained left ventricular outflow tract [V-1]) and aortic valve [V-2] velocities) during intraoperative transesophageal echocardiography (IEE). Design:Prospective study; measurements were performed on-line. Setting: University hospital. Participants:Cardiac and noncardiac surgical patients (n = 75) with recent aortic valve assessment (<3 months) undergoing general anesthesia or endotracheal intubation. Interventions: Intraoperative AVA was measured by the continuity equation using the DE technique (DE/TEE) and by planimetry (PL/TEE). Left ventricular outflow tract diameter was obtained from midesophageal views, whereas subvalvular (V-1) and valvular (V-2) velocities were obtained simultaneously using continuous-wave Doppler from transgastric views. V-1 was also obtained using pulsed-wave Doppler. Measurements were compared with AVA obtained preoperatively by the Gorlin equation during cardiac catheterization (G/CATH) or by transthoracic echocardiography using the traditional continuity equation (C/TTE) (nonsimultaneously obtained V-1 and V-2) Measurements and Main Results: A DE was obtained in 73 of 75 patients (97%). Four patients had atrial fibrillation at the time of the examination, whereas the rest were in sinus rhythm. PL/TEE was performed in 54 of 71 patients with sinus rhythm (76%). Agreement was good between DE/TEE and G/CATH (mean bias, 0.02 cm(2) [SD, 0.24 cm(2)]), and C/TTE (mean bias, -0.05 cm(2) [SD, 0.16 cm(2)]). Agreement was not as good between PL/TEE and G/CATH (mean bias, -0.07 cm(2) [SD, 0.28 cm(2)]) and C/TTE (mean bias, -0.13 cm(2) [SD, 0.30 cm(2)]). V-1 obtained by pulsed-wave Doppler and with DE closely agreed (mean bias, 0.01 m/sec [SD, 0.05 m/sec]). Conclusion: TEE evaluation of native AVA using the DE technique is feasible and in good agreement with that obtained by C/TTE and G/CATH. Compared with DE/TEE, PL/ TEE did not agree as well. Use of DE/TEE should simplify the continuity equation and may minimize errors resulting from beat-to-beat variability in stroke volume. Copyright (C) 2001 by W.B. Saunders Company. C1 Beth Israel Deaconess Med Ctr, Dept Anesthesia, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Cardiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Maslow, AD (reprint author), Rhode Isl Hosp, Dept Anesthesia, 593 Eddy St,Davol 129, Providence, RI 02903 USA. NR 43 TC 10 Z9 10 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 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD JUN PY 2001 VL 15 IS 3 BP 293 EP 299 DI 10.1053/jcan.2001.23272 PG 7 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 446JK UT WOS:000169510000004 PM 11426358 ER PT J AU Spinella-Jaegle, S Rawadi, G Kawai, S Gallea, S Faucheu, C Mollat, P Courtois, B Bergaud, B Ramez, V Blanchet, AM Adelman, G Baron, R Roman-Roman, S AF Spinella-Jaegle, S Rawadi, G Kawai, S Gallea, S Faucheu, C Mollat, P Courtois, B Bergaud, B Ramez, V Blanchet, AM Adelman, G Baron, R Roman-Roman, S TI Sonic hedgehog increases the commitment of pluripotent mesenchymal cells into the osteoblastic lineage and abolishes adipocytic differentiation SO JOURNAL OF CELL SCIENCE LA English DT Article DE sonic hedgehog; bone morphogenetic protein 2; osteoblast; adipocyte; differentiation ID TRABECULAR BONE; INDIAN HEDGEHOG; PPAR-GAMMA; PROTEINS; RECEPTOR; MARROW; SIGNAL; ADIPOGENESIS; EXPRESSION; C3H10T1/2 AB The proteins of the hedgehog (Hh) family regulate various aspects of development. Recently, members of this family have been shown to regulate skeletal formation in vertebrates and to control both chondrocyte and osteoblast differentiation. In the present study, we analyzed the effect of Sonic hedgehog (Shh) on the osteoblastic and adipocytic commitment/differentiation. Recombinant N-terminal Shh (N-Shh) significantly increased the percentage of both the pluripotent mesenchymal cell lines C3H10T112 and ST2 and calvaria cells responding to bone morphogenetic protein 2 (BMP-2), in terms of osteoblast commitment as assessed by measuring alkaline phosphatase (ALP) activity. This synergistic effect was mediated, at least partly, through the positive modulation of the transcriptional output of BMPs via Smad signaling, Furthermore, N-Shh was found to abolish adipocytic differentiation of C3H10T1/2 cells both in the presence or absence of BMP-2, A short treatment with N-Shh was sufficient to dramatically reduce the levels of the adipocytic-related transcription factors C/EBP alpha and PPAR gamma in both C3H10T1/2 and calvaria cell cultures. Given the inverse relationship between marrow adipocytes and osteoblasts with aging, agonists of the Hh signaling pathway might constitute potential drugs for preventing and/or treating osteopenic disorders. C1 Hoechst Marion Roussel, Dept Biotechnol, Bone Dis Grp, F-93230 Romainville, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Orthopaed, New Haven, CT 06510 USA. RP Roman-Roman, S (reprint author), Hoechst Marion Roussel, Dept Biotechnol, Bone Dis Grp, 111 Route Noisy, F-93230 Romainville, France. RI Roman-Roman, Sergio/K-9993-2014 OI Roman-Roman, Sergio/0000-0001-6459-2613 NR 38 TC 168 Z9 180 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN PY 2001 VL 114 IS 11 BP 2085 EP 2094 PG 10 WC Cell Biology SC Cell Biology GA 444GV UT WOS:000169392500013 PM 11493644 ER PT J AU Bostic, JQ Prince, J Brown, K Place, S AF Bostic, JQ Prince, J Brown, K Place, S TI A retrospective study of citalopram in adolescents with depression SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID JUVENILE MOOD DISORDERS; MAJOR DEPRESSION; OPEN-LABEL; FLUOXETINE TREATMENT; OPEN TRIAL; CHILDREN; SERTRALINE; MULTICENTER; PAROXETINE; EFFICACY AB Recent evidence suggests that the selective serotonin reuptake inhibitors are safe and efficacious in treating juveniles with depression. However, citalopram has not been reported in adolescents with depression. This study assessed the effectiveness and tolerability of citalopram in all adolescents with depressive disorders treated naturalistically in a community mental health center during a 1-year interval. Medical charts were retrospectively reviewed for 21 adolescents treated with citalopram for major depression (n = 14), bipolar depression (n = 4), or dysthymia (n = 3). An independent rater compared last visit to baseline depression using the Clinical Global Impression (CGI) Severity and Improvement scales. Adolescents received citalopram for an average of 128.5 +/- 84 days at a final average dose of 26.5 +/- 13.1 mg/day. Sixteen of these 21 adolescents (76%) exhibited much to very much improvement as measured by the CGI, and severity of depression diminished significantly (z = 3.007, p <0.0026). Mild side effects, including headaches, dizziness, nausea, sedation, agitation, and sweating were reported by 7 (33%) of the patients. These data suggest that citalopram may be effective, safe, and well tolerated in the treatment of adolescents with depressive disorders and that controlled trials are warranted in this population. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Child Psychiat,WACC 725, Boston, MA 02114 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. CLM Behav Hlth, Salem, NH USA. RP Bostic, JQ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Child Psychiat,WACC 725, 15 Parkman St, Boston, MA 02114 USA. NR 35 TC 16 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD SUM PY 2001 VL 11 IS 2 BP 159 EP 166 DI 10.1089/104454601750284063 PG 8 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 445JV UT WOS:000169455100006 PM 11436955 ER PT J AU Faraone, SV Pliszka, SR Olvera, RL Skolnik, R Biederman, J AF Faraone, SV Pliszka, SR Olvera, RL Skolnik, R Biederman, J TI Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: A reanalysis using drug-placebo and drug-drug response curve methodology SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DSM-III-R; DEFICIT/HYPERACTIVITY DISORDER; AUTISTIC DISORDER; CHILDREN; TRIALS AB Because methylphenidate (MPH) is currently the most widely prescribed medication for attention deficit hyperactivity disorder (ADHD), several studies have used this as the touchstone for evaluating the efficacy of a newer stimulant, Adderall. In a parallel-groups study of MPH (n = 20), Adderall (n = 20), and placebo (n = 18), Pliszka et al. (2000) reported that both medications were superior to placebo in improving parent, teacher, and clinician ratings of ADHD and associated behaviors. Compared with MPH, Adderall led to significantly more improvements in teacher and clinician ratings. The present study extends these results by addressing the issue of clinical significance using drug-placebo and drug-drug response curve analyses of the same data. The goal of this method is to answer the following questions about drug-placebo or drug-drug differences: Is the effect clinically meaningful? What does the effect tell us about individual responses? Is the effect due to symptom improvement, the prevention of worsening, or both? Our results show that the efficacy of Adderall to improve functioning is seen throughout the full range of improvement scores. In contrast, MPH showed a substantial effect for "mildly" and "much improved" but not for "very much improved." Our analyses also show that both Adderall and MPH prevent worsening of symptoms. They further suggest that, compared with the Conners Teacher Rating Scale, the Clinical Global Impressions scale may be more sensitive to improvements at the "well end" of the spectrum of functioning. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit ACC 725, 15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 16 TC 13 Z9 13 U1 1 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD SUM PY 2001 VL 11 IS 2 BP 171 EP 180 DI 10.1089/104454601750284081 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 445JV UT WOS:000169455100008 PM 11436957 ER PT J AU Palmert, MR Boepple, PA AF Palmert, MR Boepple, PA TI Variation in the timing of puberty: Clinical spectrum and genetic investigation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID GONADOTROPIN-RELEASING-HORMONE; SINGLE-NUCLEOTIDE POLYMORPHISMS; FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; HYPOGONADOTROPIC HYPOGONADISM; PRECOCIOUS PUBERTY; LINKAGE DISEQUILIBRIUM; RHESUS-MONKEY; YOUNG GIRLS; DEFICIENCY AB Human puberty begins with the reemergence of GnRH secretion from its relative quiescence during childhood, activating a cascade of pituitary-gonadal maturation. This transition begins across a wide range of ages, and the rate of subsequent sexual maturation can be quite varied. The factors that regulate the hypothalamic-pituitary-gonadaI axis and modulate the timing of puberty remain elusive, but it is clear that some regulation is under genetic control. Here, we discuss how new advances in genetic research may provide the tools to help unravel this long-standing mystery. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Boepple, PA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 5,Fruit St, Boston, MA 02114 USA. NR 40 TC 117 Z9 117 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2001 VL 86 IS 6 BP 2364 EP 2368 DI 10.1210/jc.86.6.2364 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000006 PM 11397824 ER PT J AU Miller, KK AF Miller, KK TI Androgen deficiency in women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID BONE-MINERAL DENSITY; HORMONE-BINDING GLOBULIN; POST-MENOPAUSAL WOMEN; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION; SEX STEROIDS; SURGICAL MENOPAUSE; RANCHO-BERNARDO; DEHYDROEPIANDROSTERONE-SULFATE; HYPOTHALAMIC AMENORRHEA AB Physiological and pathological processes as well as iatrogenic interventions may result in androgen deficiency compared with levels in young healthy women. Whether relative androgen deficiency results in a clinical syndrome similar to that reported in men, including osteopenia, increased fat mass, decreased libido, and diminished quality of life, has not been definitively established. However, preliminary data in postmenopausal women suggest that physiological androgen replacement therapy, which involves substantially lower doses than those used in men, may result in increased bone mineral density, increased libido, and improved quality of life. The safety of androgen preparations that result in supraphysiological levels has not been established in women and would be expected to result in hirsutism, acne, and virilization with chronic use. Androgen preparations that avoid liver metabolism and result in physiological serum androgen levels in women with androgen deficiency are not currently available, but are in development. Therefore, although widespread screening and hormone replacement for androgen deficiency cannot be recommended yet, increasing interest in this topic makes consideration of the available data important. C1 Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Miller, KK (reprint author), Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM kkmiller@partners.org FU NCRR NIH HHS [M01-RR-01066-24S2] NR 73 TC 39 Z9 43 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2001 VL 86 IS 6 BP 2395 EP 2401 DI 10.1210/jc.86.6.2395 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000011 PM 11397829 ER PT J AU Gill, S Taylor, AE Martin, KA Welt, CK Adams, JM Hall, JE AF Gill, S Taylor, AE Martin, KA Welt, CK Adams, JM Hall, JE TI Specific factors predict the response to pulsatile gonadotropin-releasing hormone therapy in polycystic ovarian syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NORMOGONADOTROPIC OLIGOAMENORRHEIC INFERTILITY; FOLLICLE-STIMULATING-HORMONE; CLOMIPHENE CITRATE INDUCTION; LUTEINIZING-HORMONE; INHIBIN-B; OVULATION INDUCTION; HYPOTHALAMIC AMENORRHEA; INSULIN-RESISTANCE; DISEASE PATIENTS; YOUNG-WOMEN AB Ovulation induction is particularly challenging in patients with polycystic ovarian syndrome (PCOS) and may be complicated by multifollicular development. Pulsatile GnRH stimulates monofollicular development in women with anovulatory infertility; however, ovulation rates are considerably lower in the subgroup of patients with PCOS. The aim of this retrospective study was to determine specific hormonal, metabolic, and ovarian morphological characteristics that predict an ovulatory response to pulsatile GnRH therapy in patients with PCOS. Subjects with PCOS were defined by chronic amenorrhea or oligomenorrhea and clinical and/or biochemical hyperandrogenism in the absence of an adrenal or pituitary disorder. At baseline; gonadotropin dynamics were assessed by 10-min blood sampling, insulin resistance by fasting insulin levels, ovarian morphology by transvaginal ultrasound, and androgen production by total testosterone levels. Intravenous pulsatile GnRH was then administered. During GnRH stimulation, daily blood samples were analyzed for gonadotropins, estradiol (E(2)), progesterone, inhibin B, and androgen levels, and serial ultrasounds were performed. Forty-one women with PCOS underwent a total of 144 ovulation induction cycles with pulsatile GnRH. Fifty-six percent of patients ovulated with 40% of ovulatory patients achieving pregnancy. Among the baseline characteristics, ovulatory cycles mere associated with lower body mass index (P < 0.05), lower fasting insulin (P = 0.02), lower 17-hydroxyprogesterone and testosterone responses to hCG (P < 0.03) and higher FSH (P < 0.05). In the first week of pulsatile GnRH treatment, E(2) and the size of the largest follicle were higher (P < 0.03), whereas androstenedione was lower (P < 0.01) in ovulatory compared with anovulatory patients. Estradiol levels of 230 pg/mL (844 pmol/L) or more and androstenedione levels of 2.5 ng/mL (8.7 nmoL/L) or less on day 4 and follicle diameter of 11 mm or more by day 7 of pulsatile GnRH treatment had positive predictive values for ovulation of 86.4%, 88.4%, and 99.6%, respectively. Ovulatory patients who conceived had lower free testosterone levels at baseline (P < 0.04). In conclusion, pulsatile GnRH is an effective and safe method of ovulation induction in a subset of patients with PCOS. Patient characteristics associated with successful ovulation in response to pulsatile GnRH include lower body mass index and fasting insulin levels, lower androgen response to hCG, and higher baseline FSH. In ovulatory patients, high free testosterone is negatively associated with pregnancy. A trial of pulsatile GnRH therapy may be useful in all PCOS patients, as E(2) and androstenedione levels on day 4 or follicle diameter on day 7 of therapy are highly predictive of the ovulatory response in this group of patients. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Hall, JE (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX-5, Boston, MA 02114 USA. EM hall.janet@mgh.harvard.edu OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-1066]; NICHD NIH HHS [P30-HD-28138, U54-HD-29164] NR 56 TC 9 Z9 11 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2001 VL 86 IS 6 BP 2428 EP 2436 DI 10.1210/jc.86.6.2428 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000016 PM 11397835 ER PT J AU Pitteloud, N Boepple, PA DeCruz, S Valkenburgh, SB Crowley, WF Hayes, FJ AF Pitteloud, N Boepple, PA DeCruz, S Valkenburgh, SB Crowley, WF Hayes, FJ TI The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: Spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GNRH-DEFICIENT MEN; FREE ALPHA-SUBUNIT; FOLLICLE-STIMULATING-HORMONE; ADRENAL HYPOPLASIA CONGENITA; LUTEINIZING-HORMONE; KALLMANNS-SYNDROME; INHIBIN-B; SECRETION; GENE; TESTOSTERONE AB Mutations in the GnRH receptor (GnRH-R) gene have been reported to cause idiopathic hypogonadotropic hypogonadism (IHH). Herein, we describe a 26-yr-old male with a mild phenotypic form of IHH, the fertile eunuch syndrome (IHH in the presence of normal testicular; size and some degree of spermatogenesis), associated with a homozygous mutation (Gln106Arg) in the GnRH-R. This mutation, located in the first extracellular loop of the GnRH-R, has been previously shown to decrease but not eliminate GnRH binding. The proband had hypogonadal testosterone levels, detectable but apulsatile gonadotropin secretion, and a normal adult male testicular size of 17 mL at baseline. After only 4 months of treatment with hCG alone, he developed sperm in his ejaculate and his wife conceived; Following cessation of hCG therapy, the patient demonstrated reversal of his hypogonadotropism as evidenced by normal adult male testosterone levels and the appearance of pulsatile luteinizing hormone secretion. This case thus expands the emerging clinical spectrum of GnRH-R mutations, provides the first genetic basis for the fertile eunuch variant of IHH. and documents the occurrence of reversible IHH in a patient with a GnRH-R mutation. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Bartlett Hall Extens 5, Boston, MA 02114 USA. EM npitteloud@partners.org RI PITTELOUD, Nelly/K-2709-2014 FU NCRR NIH HHS [MO1-RR-01066]; NICHD NIH HHS [R01-HD-15788-15, P30 HD028138, R01 HD015788, U54 HD028138, U54 HD029164]; NIDDK NIH HHS [DK-07028-24]; PHS HHS [2U54H028138] NR 41 TC 70 Z9 72 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2001 VL 86 IS 6 BP 2470 EP 2475 DI 10.1210/jc.86.6.2470 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000023 PM 11397842 ER PT J AU Welt, CK Smith, ZA Pauler, DK Hall, JE AF Welt, CK Smith, ZA Pauler, DK Hall, JE TI Differential regulation of inhibin A and inhibin B by luteinizing hormone, follicle-stimulating hormone, and stage of follicle development SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN MENSTRUAL-CYCLE; RAT GRANULOSA-CELLS; DIMERIC INHIBIN; ACTIVIN-A; OVARIAN FOLLICLES; IN-VITRO; GONADOTROPIN; SUBUNIT; WOMEN; FSH AB Inhibin B and inhibin A exhibit unique patterns of secretion across the follicular phase of the menstrual cycle. To test the hypothesis that the distinct patterns of inhibin B and inhibin A secretion result from differential regulation by LH and FSH, a series of controlled experiments was designed to dissect the specific effects of LH and FSH at distinct stages of follicle development. After GnRH agonist desensitization, women with small antral follicles were treated with recombinant human LH (rhLH), rhFSH, or rhFSH and estradiol (E(2)). rhLH or rhFSH was also administered when follicles reached the preovulatory stage in gonadotropin-stimulated or spontaneous cycles. At the small antral stage of development, rhFSH, but not rhLH, administration increased inhibin B (17.4 +/- 4.6 to 321.0 +/- 97.0 pg/mL; < 0.05), inhibin A (0.6 +/- 0.1 to 2.6 +/- 0.6 IU/mL; P < 0.05), and E(2) [15.8 +/- 3.6 to 95.3 +/- 26.9 pg/mL (58.0 +/- 13.2 to 349.8 +/- 98.7 pmol/L); P < 0.05]. The inhibin B increase preceded inhibin A by 48 h. Addition of E(2) to FSH resulted in a greater increase in inhibin B (23.2 +/- 6.4 to 865.2 +/- 294.5 pg/mL; P < 0.05) than FSH alone (P < 0.05). At the preovulatory stage, rhLH administration increased inhibin A (15.9 +/- 10.3 to 21.5 +/- 13.7 IU/mL; P < 0.05) and E(2) [669.4 +/- 285.5 to 943.6 +/- 388.1 pg/mL (2457.4 +/- 1048.1 to 3464.0 +/- 1424.7 pmol/L); P < 0.05], but not inhibin B, as did rhFSH administration in spontaneous cycles [E(2): 226.4 +/- 102.7 to 264.7 +/- 121.0 pg/mL (831.1 +/- 377.0 to 971.7 +/- 444.2 pmol/L); P < 0.05; inhibin A: 2.6 +/- 1.3 to 3.7 +/- 1.9 IU/mL; P < 0.05; and inhibin B: 76.3 +/- 32.2 to 77.6 +/- 32.8 pg/mL; P = NS]. These findings suggest that increases in both FSH and E(2) in the early follicular phase result in increased inhibin B secretion at early stages of follicle development, whereas the selective LH rise in the late follicular phase favors inhibin A secretion from more mature follicles. Thus, both differential secretion of LH and FSH and the stage of follicle development determine the patterns of inhibin A and inhibin B secretion in the normal menstrual cycle. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Dept Med, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Reprod Endocrine Sci Ctr, BHX 511,Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [K24-HD-01290, P30-HD-28138, U54-HD-29164] NR 31 TC 49 Z9 52 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2001 VL 86 IS 6 BP 2531 EP 2537 DI 10.1210/jc.86.6.2531 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000032 PM 11397851 ER PT J AU Aguiar, RCT Cox, G Pomeroy, SL Dahia, PLM AF Aguiar, RCT Cox, G Pomeroy, SL Dahia, PLM TI Analysis of the SDHD gene, the susceptibility gene for familial paraganglioma syndrome (PGL1), in pheochromocytomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID SUCCINATE-UBIQUINONE OXIDOREDUCTASE; TUMOR-SUPPRESSOR GENE; COMPLEX-II; HEREDITARY PARAGANGLIOMAS; RET PROTOONCOGENE; CHROMOSOME 11Q23; IMPRINTED GENE; CYTOCHROME-B; SHORT ARM; HETEROZYGOSITY AB Pheochromocytomas are neural crest-derived tumors that occur mostly sporadically, but may also be part of inherited syndromes. The molecular pathogenesis of sporadic pheochromocytomas remains unknown. Recently, the susceptibility gene for familial paraganglioma syndrome, a disorder embryologically related to pheochromocytomas, was characterized and shown to encode the small subunit of succinate dehydrogenase (SDHD), which is part of the mitochondrial complex II. This complex regulates oxygen-sensing signals. Importantly, hypoxic signals also appear to be related to the pathogenesis of pheothromocytomas associated with von Hippel-Lindau syndrome. We sequenced the entire coding region of the SDHD gene in a series of pheochromocytomas. Although we did not find mutations in the gene, we identified a new intronic single nucleotide polymorphism in 15% of the samples (g.97739A-->G). We also confirmed the existence of a sequence highly homologous to the SDHD complementary DNA in chromosome 1p34-36, a region commonly deleted in pheochromocytomas. Full analysis of this sequence revealed a heterozygous single base substitution in 70% of our samples that was also present in the germline. This sequence does not appear to be transcribed and is probably a processed pseudogene. Therefore, despite its chromosomal location, it is unlikely that this sequence is a target of loss of heterozygosity in pheochromocytomas. In conclusion, mutations of the SDHD gene are not a common event in this series of sporadic pheochromocytomas. The existence of SDHD pseudogenes should be considered when analyzing complementary DNA-based samples. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Dahia, PLM (reprint author), Dana Farber Canc Inst, Dept Canc Biol Adult Oncol, 44 Binney St,SM1010, Boston, MA 02115 USA. EM patricia_dahia@dfci.harvard.edu FU NICHD NIH HHS [P30-HD-18655]; NINDS NIH HHS [NS35701] NR 34 TC 41 Z9 43 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2001 VL 86 IS 6 BP 2890 EP 2894 DI 10.1210/jc.86.6.2890 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444QX UT WOS:000169412000086 PM 11397905 ER PT J AU Choo, PW Rand, CS Inui, TS Lee, MLT Canning, C Platt, R AF Choo, PW Rand, CS Inui, TS Lee, MLT Canning, C Platt, R TI Derivation of adherence metrics from electronic dosing records SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE antihypertensive agents; hypertension; patient compliance; adherence; health behavior; electronic medication monitors ID DRUG REGIMEN COMPLIANCE; MEDICATION COMPLIANCE; THERAPY; FREQUENCY AB Numerous adherence variables have been created from electronic dosing records hindering synthesis of the vast body of adherence research. To elucidate the mathematical foundation for electronic adherence monitoring and to understand how diverse electronic adherence metrics are related to each other and the underlying construct of adherence behavior. Several representative adherence metrics are derived mathematically and their relationship to the underlying consumption (or dosing event) rate analyzed. Data from a 3-month study of 286 individuals on single-drug antihypertensive therapy are then used to empirically study the statistical properties of several of these electronic adherence metrics. As suggested by their common link to the consumption (or dosing event) rate, the analyzed electronic adherence metrics were generally strongly correlated (r <-.6 and > .4). The lowest correlation (r =.15) involved the ratio of the observed number of doses to the recommended number (called average adherence), which tended to emphasize quantity consumed, and the ratio of the observed to maximum mean squared rate deviation (MSRD ratio), which focused more on dose timing. Despite their different formulations, electronic adherence variables are generally closely correlated. Adherence metrics that average the consumption rate over multiple doses (by summing up the number of doses and dividing by the monitored time) may be less sensitive to short-term fluctuations in medication intake. Metrics that are more sensitive to timing variability may thus be preferable when timing as well as quantity of dosing are of interest. (C) 2001 Elsevier Science Inc. Although reserved. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Pilgrim Hlth Care, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Choo, PW (reprint author), 181 Longwood Ave,Room 433, Boston, MA 02115 USA. FU AHRQ HHS [HS07821] NR 27 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD JUN PY 2001 VL 54 IS 6 BP 619 EP 626 DI 10.1016/S0895-4356(00)00348-6 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 437AC UT WOS:000168967200011 PM 11377123 ER PT J AU Antin, JH AF Antin, JH TI Acute graft-versus-host disease: inflammation run amok? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID MARROW 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, Boston, MA USA. RP Antin, JH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUN PY 2001 VL 107 IS 12 BP 1497 EP 1498 DI 10.1172/JCI13259 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 445TN UT WOS:000169474800003 PM 11413153 ER PT J AU Shen, Z Feng, Y Dewhirst, FE Fox, JG AF Shen, Z Feng, Y Dewhirst, FE Fox, JG TI Coinfection of enteric Helicobacter spp. and Campylobacter spp. in cats SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FLEXISPIRA-RAPPINI BACTEREMIA; SP-NOV; HOMOSEXUAL MEN; HUMAN FECES; UPSALIENSIS; GASTROENTERITIS; PREVALENCE; ANIMALS; JEJUNI; ORGANISMS AB During a 6-year period, 64 of 227 commercially reared cats had microaerobic bacteria isolated from their feces. All the isolates were initially identified as Campylobacter-like organisms based on biochemical and phenotypic characteristics. DNA extractions from 51 of these isolates were subjected to PCR using primers specific for Helicobacter spp. and Campylobacter spp. Of the isolates, 92% (47 of 51 isolates) were positive for Campylobacter spp,, 41% (21 of 51 isolates) were positive for Helicobacter spp., 33% (17 of 51 isolates) were positive for both genera, 59% (30 of 51 isolates) were positive only for Campylobacter spp., and 8% (4 of 51) were positive only for Helicobacter spp. Sixteen of the 47 Campylobacter-positive cultures were positive for more than one Campylobacter. spp. Based on a species-specific PCR assay, 83% of the isolates were identified as Campylobacter helveticus, 47% of the isolates were identified as Campylobacter upsaliensis, and 6% of the isolates were classified as Campylobacter jejuni. The 1.2-kb PCR products of the 16S rRNA genes of 19 Helicobacter species isolates were subjected to restriction fragment length polymorphism (RFLP) analysis. Of the five different RFLP patterns obtained, two clustered with Helicobacter ("Flexispira") taxon 8, one clustered with Helicobacter bilis, one clustered with Helicobacter canis, and the remaining pattern was closely related to a novel Helicobacter sp. strain isolated from a woodchuck. The sequence data for the 16S rRNA genes of 10 Helicobacter spp. validated the RFLP-based identification of these isolates. This study demonstrated that biochemical and phenotypic characteristics of microaerobic organisms in cat feces were insufficient to characterize mixed Helicobacter and Campylobacter infections. Molecular structure-based diagnostics using genus- and species-specific PCR, RFLP analysis, and 16S rRNA sequence analysis enabled the identification of multiple microaerobic species in individual animals. The clinical relevance of enteric Helicobacter and Campylobacter coinfection in cats will require further studies. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Dent Med, Dept Oral Biol, Boston, MA 02115 USA. Forsyth Inst, Dept Mol Genet, Boston, MA USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16 Rm 825, Cambridge, MA 02139 USA. FU NCI NIH HHS [CA-67529, R01 CA067529]; NCRR NIH HHS [RR-01046]; NIDCR NIH HHS [DE-10374, R01 DE010374]; NIDDK NIH HHS [DK-52413, R01 DK052413, R56 DK052413] NR 57 TC 53 Z9 54 U1 0 U2 3 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 JUN PY 2001 VL 39 IS 6 BP 2166 EP 2172 DI 10.1128/JCM.39.6.2166-2172.2001 PG 7 WC Microbiology SC Microbiology GA 439ED UT WOS:000169097100021 PM 11376052 ER PT J AU Mattos-Graner, RO Li, YH Caufield, PW Duncan, M Smith, DJ AF Mattos-Graner, RO Li, YH Caufield, PW Duncan, M Smith, DJ TI Genotypic diversity of mutans streptococci in Brazilian nursery children suggests horizontal transmission SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INITIAL ACQUISITION; CARIES EXPERIENCE; DENTAL-CARIES; PREVALENCE; FAMILIES; COLONIZATION; ASSOCIATION; INFECTION; FIDELITY; INFANTS AB Streptococcus mutans strains were isolated from cohorts of Brazilian nursery school children and genotyped by arbitrarily primed PCR and restriction fragment length polymorphism analysis. Of 24 children,vith two to five S. mutans isolates, 29% carried two or more genotypes. The presence of matching genotypes of S. mutans among children attending one nursery suggests horizontal transmission. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Univ Alabama, Sch Dent, Dept Oral Biol, Birmingham, AL 35294 USA. RP Smith, DJ (reprint author), Forsyth Inst, Dept Immunol, 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 DE006153] NR 26 TC 55 Z9 68 U1 0 U2 3 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 JUN PY 2001 VL 39 IS 6 BP 2313 EP 2316 DI 10.1128/JCM.39.6.2313-2316.2001 PG 4 WC Microbiology SC Microbiology GA 439ED UT WOS:000169097100049 PM 11376080 ER PT J AU Gabrilove, JL Cleeland, CS Livingston, RB Sarokhan, B Winer, E Einhorn, LH AF Gabrilove, JL Cleeland, CS Livingston, RB Sarokhan, B Winer, E Einhorn, LH TI Clinical evaluation of once-weekly dosing of epoetin alfa in chemotherapy patients: Improvements in hemoglobin and quality of life are similar to three-times-weekly dosing SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; OF-LIFE; FUNCTIONAL ASSESSMENT; COMMUNITY ONCOLOGY; CANCER; ANEMIA; THERAPY; OUTCOMES; FATIGUE; IMPACT AB purpose: To prospectively evaluate the effectiveness, safety, and clinical benefit. of once-weekly epoetin alfa therapy as an adjunct to chemotherapy in anemic cancer patients. Patients and Methods: A total of 3,012 patients with nonmyeloid malignancies who received chemotherapy were enrolled onto this multicenter, open-label, nonrandomised study conducted in 600 United States community-based practices. patients received epoetin alfa 60,000 U once weekly, which could be increased to 50,000 U once weekly after 4 weeks dependent on hemoglobin response. Treatment was continued for a maximum of 16 weeks. Results: Among the 2,964 patients assessable for efficacy, epoetin alfa therapy resulted in significant increases in hemoglobin levels, decreases in transfusion requirements, and improvements in functional status and fatigue as assessed by the linear analog scale assessment (energy level, ability to perform daily activities, and overall quality of life) and the anemia subscale of the Functional Assessment of Cancer Therapy-Anemia questionnaire. Improvements in quality-of-life parpameters correlated significantly (P < .001) with increased hemoglobin levels. The direct relationship between hemoglobin and quality-of-life improvement was sustained during the 16-week study period, which is similar to findings of large community-based trials of three-times-weekly dosing. Once-weekly epoetin alfa was well tolerated, with most adverse events attributed to the underlying disease or concomitant chemotherapy, Conclusion: The results from this large, prospective, community-based trial suggest that once-weekly epoetin alfa therapy increases hemoglobin levels, decreases transfusion requirements, and improves quality of life in patients with cancer and anemia who undergo concomitant chemotherapy, Based on the results of this study, the clinical benefits and the adverse event profile of once-weekly epoetin alfa therapy in community-based practice are similar to there observed in the historical experience with the three-times-weekly dosage schedule. C1 Mt Sinai Med Ctr, New York, NY 10029 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Washington, Seattle, WA 98195 USA. Ortho Biotech Prod LP, Raritan, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. RP Gabrilove, JL (reprint author), Mt Sinai Med Ctr, 1 Gustave L Levy Pl, New York, NY 10029 USA. NR 19 TC 431 Z9 445 U1 0 U2 1 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 JUN 1 PY 2001 VL 19 IS 11 BP 2875 EP 2882 PG 8 WC Oncology SC Oncology GA 438BN UT WOS:000169034000015 PM 11387360 ER PT J AU Tolcher, AW Eckhardt, SG Kuhn, J Hammond, L Weiss, G Rizzo, J Aylesworth, C Hidalgo, M Patnaik, A Schwartz, G Felton, S Campbell, E Rowinsky, EK AF Tolcher, AW Eckhardt, SG Kuhn, J Hammond, L Weiss, G Rizzo, J Aylesworth, C Hidalgo, M Patnaik, A Schwartz, G Felton, S Campbell, E Rowinsky, EK TI Phase I and pharmacokinetic study of NSC 655649, a rebeccamycin analog with topoisomerase inhibitory properties SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BODY-SURFACE AREA; ANTIMICROBIAL PROPERTIES; DNA; ANTITUMOR; INDOLOCARBAZOLES; CLEAVAGE AB Purpose: To assess the feasibility of administering NSC 655649, a water-soluble, rebeccamycin analog with topoisomerase inhibitory properties, as a brief intravenous (IV) infusion once every 3 weeks and to determine the maximum-tolerated dose (MTD) of NSC 655649, characterize its pharmacokinetic behavior, and seek preliminary evidence of antitumor activity. Patients and Methods: Patients with advanced solid malignancies were treated with escalating doses of NSC 655649 administered over 30 to 60 minutes IV once every 3 weeks. An accelerated dose-escalation method was used to guide dose escalation. After three patients were treated at the first dose level, doses were escalated in increments that ranged up to 150% using single patient cohorts until moderate toxicity was observed, when a more conservative dose-escalation scheme was invoked. MTD was defined as the highest dose level at which the incidence of dose-limiting toxicity did not exceed 20%. MTD was determined for both minimally pretreated (MP) and heavily pretreated (HP) patients. plasma and urine were sampled to characterize the pharmacokinetic and excretory behavior of NSC 655649. Results: Forty-five patients were treated with 130 courses of NSC 655649 at doses ranging from 20 mg/m(2) to 744 mg/m(2). Myelosuppression was the principal toxicity. Severe neutropenia, which was often associated with thrombocytopenia, was unacceptably high in HP and MP patients treated at 572 mg/m(2) and 744 mg/m(2), respectively. Nausea, vomiting, and diarrhea were common but rarely severe. The pharmacokinetics of NSC 655649 were dose dependent and fit a three-compartment model, The clearance and terminal elimination half-lives for NSC 655649 averaged 7.57 (SD = 4.2) L/h/m(2) and 48.85 (50 = 23.65) hours, respectively. Despite a heterogeneous population of MP and HP patients, the magnitude of drug exposure correlated well with the severity of myelosuppression. Antitumor activity was observed in two HP ovarian cancer patients and one patient with a soft tissue sarcoma refractory to etoposide and doxorubicin, Conclusion: Recommended phase II doses are 500 mg/m(2) and 572 mg/m(2) IV once every 3 weeks for HP and MP patients, respectively. The absence of severe nonhematologic toxicities, the encouraging antitumor activity in HP patients, and the unique mechanism of antineoplastic activity of NSC 655649 warrant further clinical development. (C) 2001 by American Society of Clinical Oncology. C1 Inst Drug Dev, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Brooke Army Med Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. RP Tolcher, AW (reprint author), Inst Drug Dev, Canc Therapy & Res Ctr, 8122 Datapoint Dr,Ste 250, San Antonio, TX 78229 USA. RI HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 FU NCI NIH HHS [5P30 CA54174, U01 CA69853]; NCRR NIH HHS [MO1 RR01346-19] NR 19 TC 29 Z9 29 U1 0 U2 2 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 JUN 1 PY 2001 VL 19 IS 11 BP 2937 EP 2947 PG 11 WC Oncology SC Oncology GA 438BN UT WOS:000169034000022 PM 11387367 ER PT J AU Polyak, K Riggins, GJ AF Polyak, K Riggins, GJ TI Gene discovery using the serial analysis of gene expression technique: Implications for cancer research SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; C-MYC; COLORECTAL-CANCER; DENDRITIC CELLS; HUMAN MONOCYTES; BREAST-CANCER; BETA-CATENIN; P53 PATHWAY; CYCLIN D1; SAGE AB Cancer is a genetic disease. As such, our understanding of the pathobiology of tumors derives from analyses of the genes whose mutations are responsible for those tumors. The cancer phenotype, however, likely reflects the changes in the expression patterns of hundreds or even thousands of genes that occur as a consequence of the primary mutation of an oncogene or a tumor suppressor gene. Recently developed functional genomic approaches, such as DNA microarrays and serial analysis of gene expression (SAGE), have enabled researchers to determine the expression level of every gene in a given cell population, which represents that cell population's entire transcriptome, The most attractive feature of SAGE is its ability to evaluate the expression pattern of thousands of genes in a quantitative manner without prior sequence information. This feature has been exploited in three extremely powerful applications of the technology: the definition of transcriptomes, the analysis of differences between the gene expression patterns of cancer cells and their normal counterparts, and the identification of downstream targets of oncogenes and tumor suppressor genes, Comprehensive analyses of gene expression not only will further understanding of growth regulatory pathways and the processes of tumorigenesis but also may identify new diagnostic and prognostic markers as well as potential targets for therapeutic intervention. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. FU PHS HHS [S98-146A] NR 74 TC 86 Z9 94 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 JUN 1 PY 2001 VL 19 IS 11 BP 2948 EP 2958 PG 11 WC Oncology SC Oncology GA 438BN UT WOS:000169034000023 PM 11387368 ER PT J AU Craig, RG Boylan, R Yip, J Bamgboye, P Koutsoukos, J Mijares, D Ferrer, J Imam, M Socransky, SS Haffajee, AD AF Craig, RG Boylan, R Yip, J Bamgboye, P Koutsoukos, J Mijares, D Ferrer, J Imam, M Socransky, SS Haffajee, AD TI Prevalence and risk indicators for destructive periodontal diseases in 3 urban American minority populations SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE ethnicity; periodontal diseases; subgingival microbiota; risk indicators; social economic status ID DWELLING OLDER ADULTS; ATTACHMENT LOSS; SUBGINGIVAL MICROBIOTA; UNITED-STATES; CIGARETTE-SMOKING; CLINICAL STATUS; TOOTH LOSS; RACE; PLAQUE; SUPRAGINGIVAL AB Background, aims: Destructive periodontal diseases have been reported disproportionately more prevalent and severe in African-Americans relative to other American populations. Differences in subgingival microbiota and host immune response have also been reported for African-Americans, implying that risk factors for disease progression may also differ for these populations. Since it is not clear whether these differences are truly genetic or due to confounding variables such as social economic status, we examined a series of clinical, environmental, demographic, and microbiologic features associated with periodontal disease status in a group of 185 urban minority subjects resident within the greater New York metropolitan area. Methods: The study population consisted of 56 Asian-American, 7 1 African-American and 58 Hispanic subjects. Clinical data recorded included pocket depth, attachment level, gingival erythema, bleeding upon probing, suppuration, and the presence of supragingival plaque. Environmental and demographic data recorded included smoking history, years resident in the United states, whether the subject reported a private dentist and occupational status. subgingival plaque was sampled from the mesial aspect of all teeth exclusive of third molars and the levels of 40 subgingival species enumerated using checkerboard DNA-DNA hybridization. Results: The African-American group had more missing teeth, deeper periodontal pocket depth and more attachment loss than the Asian-American or Hispanic groups. However, the African-American group were less likely to report having a private dentist, had a greater proportion of smokers and a greater proportion of unskilled individuals. The profile of subgingival species differed among the three ethnic/racial groups with A. actinomycetemcomitans, N. mucosa, S. noxia and T. socranskii significantly elevated in the Asian-American group and P. micros significantly elevated in the African-American group. When subset by occupational status, numbers of missing teeth, pocket depth, attachment level and prior disease activity were all found increased in the unskilled relative to the professional group. Local factors including the mean % of sites with plaque, marginal gingival erythema, bleeding upon probing and suppuration were also elevated in the unskilled group. The microbial profile differed among the 3 occupational groups with the unskilled group having elevated numbers of species associated with destructive periodontal diseases. Conclusions: Although greater destructive periodontal disease prevalence and severity were found in the African-American group, these results suggest that environmental and demographic variables, such as occupational status, may have a greater influence on risk indicators associated with disease prevalence and progression in these populations. C1 NYU, Coll Dent, Div Basic & Surg Sci, New York, NY 10010 USA. Forsyth Inst, Div Basic & Surg Sci, Boston, MA USA. RP Craig, RG (reprint author), NYU, Coll Dent, Div Basic & Surg Sci, 345 East 24th St, New York, NY 10010 USA. FU NIDCR NIH HHS [DE 04881, P20 DE 10593] NR 49 TC 44 Z9 46 U1 0 U2 3 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 JUN PY 2001 VL 28 IS 6 BP 524 EP 535 DI 10.1034/j.1600-051x.2001.028006524.x PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 434GX UT WOS:000168807700004 PM 11350519 ER PT J AU Niederman, R Westernoff, T Lee, C Mark, LL Kawashima, N Ullman-Culler, M Dewhirst, FE Paster, BJ Wagner, DD Mayadas, T Hynes, RO Stashenko, P AF Niederman, R Westernoff, T Lee, C Mark, LL Kawashima, N Ullman-Culler, M Dewhirst, FE Paster, BJ Wagner, DD Mayadas, T Hynes, RO Stashenko, P TI Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE transgenic/knockout; adhesion molecules; infectious immunity; bacteria; cytokines ID RAPIDLY PROGRESSIVE PERIODONTITIS; LEUKOCYTE ADHESION DEFICIENCY; GINGIVAL CREVICULAR FLUID; DOUBLE MUTANT MICE; P-SELECTIN; BONE LOSS; SUBGINGIVAL MICROFLORA; MYOCARDIAL-INFARCTION; NEUTROPHIL FUNCTION; MOUSE AB Background: Retrospective and correlation studies suggest that early-onset periodontal disease may be due to a deficiency in phagocyte function, a pathogenic oral biofilm, and/or dysregulated gingival cytokine expression. Increased susceptibility to periodontal disease is therefore thought to result from multiple risk factors. Methods: We tested this hypothesis prospectively using PIE-selectin adhesion molecule deficient mice that mimic the human syndrome leukocyte adhesion deficiency II. Results: Our studies demonstrate that, in comparison to wild type animals, P/E-/- mice exhibit: spontaneous, early onset alveolar bone loss which is significant by 6 weeks of age; a in-fold elevation in bacterial colonization of their oral cavities; and elevated gingival tissue levels of the bone resorptive cytokine IL-1 alpha. Alveolar bone loss is completely prevented by prophylactic antibiotic therapy. Conclusions: These experiments provide the first prospective evidence for the multiple risk factor hypothesis of periodontal disease, and validate the first animal model for early onset periodontitis in which both the microbiota and host response can be systematically manipulated. P/E-/- animals should be useful in testing the virulence of putative periodontal pathogens, in determining the role of host resistance factors in periodontitis, in exploring the proposed relationship(s) between infection mediated alveolar bone loss and systemic health disorders, and exploring their genetic relationships. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Periodontol, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Ctr Canc Res, Dept Biol, Cambridge, MA USA. Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Niederman, R (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 The Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE09018, DE11664]; PHS HHS [P0141484] NR 47 TC 34 Z9 36 U1 0 U2 3 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 JUN PY 2001 VL 28 IS 6 BP 569 EP 575 DI 10.1034/j.1600-051x.2001.028006569.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 434GX UT WOS:000168807700010 PM 11350525 ER PT J AU Fava, M Dunner, DL Greist, JH Preskorn, SH Trivedi, MH Zajecka, J Cohen, M AF Fava, M Dunner, DL Greist, JH Preskorn, SH Trivedi, MH Zajecka, J Cohen, M TI Efficacy and safety of mirtazapine in major depressive disorder patients after SSRI treatment failure: An open-label trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 152nd Annual Meeting of the American-Psychiatric-Association CY MAY 15-20, 1999 CL WASHINGTON, D.C. SP Amer Psychiat Assoc ID QUESTIONNAIRE; TOLERABILITY AB Objective: To evaluate the efficacy and safety of mirtazapine in depressed outpatients who have shown nonresponse or intolerance to selective serotonin reuptake inhibitor (SSRI) therapy. Method: In this open-label, 8-week; study, the efficacy and safety of mirtazapine among 103 outpatients with DSM-IV major depressive disorder who had failed previous therapy with an SSRI (fluoxetine, paroxetine, or sertraline) were evaluated. The primary efficacy measure was the 17-item Hamilton Rating Scale for Depression (HAM-D-17), and safety assessments included reported adverse events, routine laboratory assessments, physical examinations, and assessments of vital signs. A 4-day washout period followed by mirtazapine treatment was compared with an immediate switch from the SSRI to mirtazapine. Results: Based un mean HAM-D-17 scores at endpoint and response rates of 48% based on the criterion of greater than or equal to 50% reduction in HAM-D-17 score, mirtazapine was found to be an effective treatment fur a substantial proportion of patients for whom an SSRI was ineffective and/or poorly tolerated. Mirtazapine was well tolerated, with sedation and appetite increase/weight gain the most commonly reported adverse events. In addition, no difference in efficacy, safety, or tolerability was observed fur patients undergoing an immediate switch from an SSRI (after having been tapered to the minimal effective dose) to mirtazapine, compared with those undergoing the imposition of a 4-day drug-free washout. Conclusion: These results suggest that an immediate switch to mirtazapine may be a valid therapeutic option among patients who cannot tolerate or do not respond to SSRIs. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Healthcare Technol Syst LLC, Madison, WI USA. Inst Psychiat Res, Wichita, KS USA. Univ Texas, SW Med Sch, Dept Psychiat, Dallas, TX 75230 USA. Rush Presbyterian Hosp, Chicago, IL USA. Organon Inc, W Orange, NJ USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, ACC 812,15 Parkman St, Boston, MA 02114 USA. RI Preskorn, Sheldon/L-9839-2016 NR 13 TC 66 Z9 67 U1 0 U2 2 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2001 VL 62 IS 6 BP 413 EP 420 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 453MD UT WOS:000169918900003 PM 11465517 ER PT J AU Smith, SR Hilsenroth, MJ AF Smith, SR Hilsenroth, MJ TI Discriminative validity of the MacAndrew Alcoholism Scale with cluster B personality disorders SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT Midwinter Meeting of the Society-for-Personality-Assessment CY FEB, 1998 CL BOSTON, MASSACHUSETTS SP Soc Personal Assessment DE MacAndrew Alcoholism Scale; personality disorders; MMPI-2 ID SUBSTANCE-ABUSE; ANTISOCIAL PERSONALITY; COMORBIDITY; INPATIENTS; DIAGNOSIS; MMPI-2 AB This study was designed to assess the ability of the Minnesota Multiphasic Personality Inventory (MMPI-2) MacAndrew Alcoholism Scale (MAC-R) to differentiate between outpatients with personality disorders with Substance-Related Disorders (SRDs) and without SRDs. MMPI-2 validity clinical, and MAC-R scale scores were compared in an SRD Cluster B group (comprised of Narcissistic. Antisocial. Borderline, and Histrionic: n = 15), a non-SRD Cluster B group (n = 33), and a non-SRD group with personality disorders from Clusters A and C (n = 18). Results revealed that the substance-abusing Cluster B group scored significantly higher on the MAC-R (p < .0001) as well as the Psychopathic Deviate scale (p < .01). Dimensional analyses illustrated that MAC-R scores were related to the presence of an SRD diagnosis (rpb = .70, p < .0001) and diagnostic criteria for Antisocial Personality Disorder (r = .60. p < .0001). Stepwise regression revealed that (in order of magnitude) the presence of a substance-abuse diagnosis followed by diagnostic criteria for Antisocial and Histrionic Personality Disorders were most related to MAC-R scores(R = .78. R-2 = .60). This indicates that the MAC-R may be more related to the presence of an SRD than has been suggested, and when used in outpatient settings as MacAndrew (1965) intended, the MAC-R may be useful as a screening device for assessing SRD among outpatients with Axis Il psychopathology. (C) 2001 John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Arkansas, Fayetteville, AR 72701 USA. RP Smith, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,ACC 812, Boston, MA 02114 USA. NR 36 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD JUN PY 2001 VL 57 IS 6 BP 801 EP 813 DI 10.1002/jclp.1050 PG 13 WC Psychology, Clinical SC Psychology GA 436PK UT WOS:000168944100008 PM 11344466 ER PT J AU Murphy, CM O'Farrell, TJ Fals-Stewart, W Feehan, M AF Murphy, CM O'Farrell, TJ Fals-Stewart, W Feehan, M TI Correlates of intimate partner violence among male alcoholic patients SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID MARITAL VIOLENCE; DOMESTIC VIOLENCE; NEWLYWED COUPLES; DRINKING; AGGRESSION; BEHAVIOR; SCALES; QUESTIONNAIRE; RELIABILITY; ADJUSTMENT AB Male-to-female partner violence was investigated in heterosexual couples with an alcoholic male partner. Partner violent (PV) alcoholic patients (n = 183), when compared with nonviolent (NV) alcoholic patients (n = 120), had more antisocial personality characteristics, greater alcohol problem severity, greater use of other drugs, higher relationship distress, and stronger beliefs in the link between alcohol consumption and relationship problems. Demographic factors did not account for these PV-NV differences. Relationship distress and alcohol problem severity had independent associations with partner violence. Relationship adjustment and drug use remained significantly associated with partner violence, whereas alcohol problem severity did not. after controlling for patient antisocial traits. Beliefs in the link between drinking and relationship problems were associated with partner violence independent of other clinical factors. C1 Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21250 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. VA Boston Healthcare Syst, Brockton, MA USA. SUNY Buffalo, Res Inst Addict, Buffalo, NY 14260 USA. RP Murphy, CM (reprint author), Univ Maryland Baltimore Cty, Dept Psychol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. FU NIAAA NIH HHS [AA10356, AA10796, AA08637] NR 78 TC 79 Z9 81 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD JUN PY 2001 VL 69 IS 3 BP 528 EP 540 DI 10.1037//0022-006X.69.3.528 PG 13 WC Psychology, Clinical SC Psychology GA 470LB UT WOS:000170872500018 PM 11495182 ER PT J AU Pontius, AA AF Pontius, AA TI Two bankrobbers with "antisocial" and "schizoid/avoidant" personality disorders, comorbid with partial seizures: Temporal lobe epilepsy and limbic psychotic trigger reaction, respectively SO JOURNAL OF DEVELOPMENTAL AND PHYSICAL DISABILITIES LA English DT Article DE antisocial and schizoid/avoidant personality disorders; diagnostic overshadowing; partial temporo-limbic seizures; atavistic regression; criminality; childhood head injury ID DEVELOPMENTAL-DISABILITIES; PSYCHIATRIC-DISORDERS; QUESTIONABLE ASPECTS; HOMICIDE AB "Diagnostic overshadowing" is illustrated by, two cases of unplanned, motiveless bank robbery, initially merely attributed to "antisocoial" or "schizoid/ avoidant" (loner) personality disorder, respectively. Both disorders, however, were comorbid with their potentially unobservable counterparts, with brief partial seizures, supported by both men's abnormal scalp-EEG's, their symptomatology with psychosis, and their histories of closed head injury in childhood. Such injuries are known to render particularly the temporo-limbic brain system susceptible to Inter partial seizure: Mr. A. had temporal lobe epilepsy (TLE) with stereotypic auditory command hallucinations and clouding of consciousness. (His past "antisocial" aggressive behavior might also have reflected TLE-related inter-ictal events.) Mr. B. had the symptomatology proposed as limbic psychotic trigger reaction (LPTR). Mr. B, a social loner, typically ruminated on past intermittent moderate stresses, a specific precondition of seizure kindling ultimately, elicited by a specific stimulus, resembling his past hurts. As is typical for LPTR, Mr B. had no clouding of consciousness and no amnesia for his atavistically regressive acts, committed with pat affect, nausea, and fleeting delusions of grandeur (being gifted like Rembrandt). C1 Harvard Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Pontius, AA (reprint author), Waldschmidt St 6, D-60316 Frankfurt, Germany. NR 18 TC 7 Z9 7 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1056-263X J9 J DEV PHYS DISABIL JI J. Dev. Phys. Disabil. PD JUN PY 2001 VL 13 IS 2 BP 191 EP 197 DI 10.1023/A:1016617526205 PG 7 WC Rehabilitation SC Rehabilitation GA 434VX UT WOS:000168837500007 ER PT J AU Frank, MS Schultz, T Dreyer, K AF Frank, MS Schultz, T Dreyer, K TI Integrating digital educational content created and stored within disparate software environments: An extensible markup language (XML) solution in real-world use SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Computer-Applications-in-Radiology CY MAY 03-06, 2001 CL SALT LAKE CITY, UTAH SP Soc Comp Applicat Radiol AB Objective: To provide a standardized and scaleable mechanism for exchanging digital radiologic educational content between software systems that use disparate authoring, storage, and presentation technologies. Materials/Methods: Our institution uses two distinct software systems for creating educational content for radiology. Each system is used to create in-house educational content as well as commercial educational products. One system is an authoring and viewing application that facilitates the input and storage of hierarchical knowledge and associated imagery, and is capable of supporting a variety of entity relationships. This system is primarily used for the production and subsequent viewing of educational CD-ROMS. Another software system is primarily used for radiologic education on the world wide web. This system facilitates input and storage of interactive knowledge and associated imagery, delivering this content over the internet in a Socratic manner simulating in-person interaction with an expert. A subset of knowledge entities common to both systems was derived. An additional subset of knowledge entities that could be bidirectionally mapped via algorithmic transforms was also derived. An extensible markup language (XML) object model and associated lexicon were then created to represent these knowledge entities and their interactive behaviors. Forward-looking attention was exercised in the creation of the object model in order to facilitate straight-forward future integration of other sources of educational content. XML generators and interpreters were written for both systems. Results: Deriving the XML object model and lexicon was the most critical and time-consuming aspect of the project. The coding of the XML generators and interpreters required only a few hours for each environment. Subsequently, the transfer of hundreds of educational cases and thematic presentations between the systems can now be accomplished in a matter of minutes. The use of algorithmic transforms results in nearly 100% transfer of context as well as content, thus providing "presentation-ready" outcomes. Conclusion:The automation of knowledge exchange between dissimilar digital teaching environments magnifies the efforts of educators and enriches the learning experience for participants. XML is a powerful end useful mechanism for transfering educational content, as well as the context and interactive behaviors of such content, between disparate systems. Copyright (C) 2001 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Frank, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 0 Emerson Pl,Suite 3E, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD JUN PY 2001 VL 14 IS 2 SU 1 BP 92 EP 97 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 444MX UT WOS:000169404200024 PM 11442133 ER PT J AU Frank, MS Schultz, T Dreyer, K AF Frank, MS Schultz, T Dreyer, K TI Integrating digital teaching-file systems with off-the-shelf presentation software to facilitate speaker-led conferences SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Computer-Applications-in-Radiology CY MAY 03-06, 2001 CL SALT LAKE CITY, UTAH SP Soc Comp Applicat Radiol ID DATABASE AB Objective: Develop methods for automated transfer of images and associated text from a teaching-file repository into presentation material for speaker-led conferences. Materials/Methods: Our institution uses a Microsoft Windows (Microsoft Corp, Redmond, WA) software application to maintain a digital teaching-file database that can store and retrieve content in a case-centric fashion. Virtually any number of images can be stored with any given case. Cases and their associated images can be retrieved via a module that supports searches by American College of Radiology (ACR) code and by free-text Boolean queries on the history, findings, diagnosis, and discussion components of a case. In addition to the software system serving directly as an interactive teaching tool, the digital teaching file itself serves as an image repository and resource for attending radiologists who create their own presentations and lectures. To better support this use, software modules were developed for interprocess communication and automated creation of Powerpoint slides. These modules are fully integrated with the teaching-file software application. A single image or a set of selected images can be automatically made into individual slides with two mouse clicks. Images are automatically centered and optimally sized. A slide title is automatically rendered from the user's preference of the case history or diagnosis (stored with the case), or via the entry of free-form text. We describe the programming techniques that are used, as well as how several features of the operating system and Powerpoint itself can be integrated with a customized software application to facilitate this objective. Results: The creation of presentation-ready Powerpoint slides is fully automated from within our teaching-file application, and the time required to create a presentation compared to the conventional method of manually seeking and inserting files from within Powerpoint itself, on a per-slide basis, is drastically reduced. The benefits are magnified by having all imagery stored within an organized end searchable database system so that desired images can be easily located. Conclusion: A digital teaching-file system can serve as a useful image repository for purposes ancillary to direct computerized instruction. Software that supports these uses, such as the automated creation of presentation material for speaker-led conferences, facilitates the radiologist's role as an educator. Copyright (C) 2001 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Frank, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 0 Emerson Pl,Suite 3E, Boston, MA 02114 USA. NR 3 TC 3 Z9 4 U1 3 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD JUN PY 2001 VL 14 IS 2 SU 1 BP 98 EP 101 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 444MX UT WOS:000169404200025 PM 11442134 ER PT J AU Frank, MS Dreyer, K AF Frank, MS Dreyer, K TI Beyond the electronic textbook model: Software techniques to make on-line educational content dynamic SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Computer-Applications-in-Radiology CY MAY 03-06, 2001 CL SALT LAKE CITY, UTAH SP Soc Comp Applicat Radiol AB Objective: We describe a working software technology that enables educators to incorporate their expertise and teaching style into highly interactive and Socratic educational material for distribution on the world wide web. Materials/Methods: A graphically oriented interactive authoring system was developed to enable the computer novice to create and store within a database his or her domain expertise in the form of electronic knowledge. The authoring system supports and facilitates the input and integration of several types of content, including free-form, stylized text, miniature and full-sized images, audio, and interactive questions with immediate feedback. The system enables the choreography and sequencing of these entities for display within a web page as well as the sequencing of entire web pages within a case-based or thematic presentation. Images or segments of text can be hyperlinked with point-and-click to other entities such as adjunctive web pages, audio, or other images, cases, or electronic chapters. Miniature (thumbnail) images are automatically linked to their full-sized counterparts. The authoring system contains a graphically oriented word processor, an image editor, and capabilities to automatically invoke and use external image-editing software such as Photo-shop. The system works in both local area network (LAN) and internet-centric environments. An internal metalanguage (invisible to the author but stored with the content) was invented to represent the choreographic directives that specify the interactive delivery of the content on the world wide web. A database schema was developed to objectify and store both this electronic knowledge and its associated choreographic metalanguage. A database engine was combined with page-rendering algorithms in order to retrieve content from the database and deliver it on the web in a Socratic style, assess the recipient's current fund of knowledge, and provide immediate feedback, thus stimulating in-person interaction with a human expert. Results: This technology enables the educator to choreograph a stylized, interactive delivery of his or her message using multimedia components assembled in virtually any order, spanning any number of web pages for a given case or theme. An educator can thus exercise precise influence on specific learning objectives, embody his or her personal teaching style within the content, and ultimately enhance its educational impact. Conclusion: The described technology amplifies the efforts of the educator and provides a more dynamic and enriching learning environment for web-based education. Copyright (C) 2001 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Frank, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Zero Emerson Pl,Suite 3E, Boston, MA 02114 USA. NR 0 TC 11 Z9 11 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 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD JUN PY 2001 VL 14 IS 2 SU 1 BP 108 EP 112 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 444MX UT WOS:000169404200028 PM 11442066 ER PT J AU Frank, MS Dreyer, K AF Frank, MS Dreyer, K TI Empowering radiologic education on the Internet: A new virtual website technology for hosting interactive educational content on the world wide web SO JOURNAL OF DIGITAL IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Computer-Applications-in-Radiology CY MAY 03-06, 2001 CL SALT LAKE CITY, UTAH SP Soc Comp Applicat Radiol AB Objective: We describe a virtual web site hosting technology that enables educators in radiology to emblazon and make available for delivery on the world wide web their own interactive educational content, free from dependencies on in-house resources and policies. Materials/Methods: This suite of technologies includes a graphically oriented software application, designed for the computer novice, to facilitate the input, storage, and management of domain expertise within a database system. The database stores this expertise as choreographed and interlinked multimedia entities including text, imagery, interactive questions, and audio. Case-based presentations or thematic lectures can be authored locally, previewed locally within a web browser, then uploaded at will as packaged knowledge objects to an educator's (or department's) personal web site housed within a virtual server architecture. This architecture can host an unlimited number of unique educational web sites for individuals or departments in need of such service. Each virtual site's content is stored within that site's protected back-end database connected to Internet Information Server (Microsoft Corp, Redmond WA) using a suite of Active Server Page (ASP) modules that incorporate Microsoft's Active Data Objects (ADO) technology. Each person's or department's electronic teaching material appears as an independent web site with different levels of access- controlled by a username-password strategy-for teachers and students. There is essentially no static hypertext markup language (HTML). Rather, all pages displayed for a given site are rendered dynamically from case-based or thematic content that is fetched from that virtual site's database. The dynamically rendered HTML is displayed within a web browser in a Socratic fashion that can assess the recipient's current fund of knowledge while providing instantaneous user-specific feedback. Each site is emblazoned with the logo and identification of the participating institution. Individuals with teacher-level access can use a web browser to upload new content as well as manage content already stored on their virtual site. Each virtual site stores, collates, and scores participants' responses to the interactive questions posed on line. Conclusion: This virtual web site strategy empowers the educator with an end-to-end solution for creating interactive educational content and hosting that content within the educator's personalized and protected educational site on the world wide web, thus providing a valuable outlet that can magnify the impact of his or her talents and contributions. Copyright (C) 2001 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Frank, MS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Zero Emerson Pl,Suite 3E, Boston, MA 02114 USA. NR 0 TC 12 Z9 12 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 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD JUN PY 2001 VL 14 IS 2 SU 1 BP 113 EP 116 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 444MX UT WOS:000169404200029 PM 11442067 ER PT J AU Jonsson, KB Mannstadt, M Miyauchi, A Yang, IM Stein, G Ljunggren, O Juppner, H AF Jonsson, KB Mannstadt, M Miyauchi, A Yang, IM Stein, G Ljunggren, O Juppner, H TI Extracts from tumors causing oncogenic osteomalacia inhibit phosphate uptake in opossum kidney cells SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID X-LINKED HYPOPHOSPHATEMIA; PEX GENE; P-I; HORMONE; TRANSPORT; MICE; BIOACTIVITY; RICKETS; MOUSE AB In oncogenic osteomalacia (OOM), a tumor produces an unknown substance that inhibits phosphate reabsorption in the proximal tubules. This causes urinary phosphate wasting and, as a consequence, hypophosphatemic osteomalacia. To characterize this poorly understood biological tumor activin we generated aqueous extracts from several OOM tumors. Extracts from three of four tumors inhibited, dose- and time-dependently, P-32-orthophosphate uptake by opossum kidney (OK) cells; maximum inhibition was about 45% of untreated control Further characterization revealed that the factor is resistant to heat and several proteases, and that it has a low molecular weight. The tumor extracts also stimulated cAMP accumulation in OK cells, but not in osteoblastic ROS 17/2.8 and UMR106 cells, or in LLC-PK1 kidney cells expressing the parathyroid hormone (PTH)/PTH-related peptide receptor or the PTH-2 receptor. HPLC: separation of low molecular weight fractions of the tumor extracts revealed that the flow-through of all three positive tumor extracts inhibited P-32 uptake and stimulated cAMP accumulation in OK cells. Additionally, a second peak with inhibitory activity on phosphate transport, but without cAMP stimulatory activity, was identified in the most potent tumor extract. We have concluded that several low molecular weight molecules with the ability to inhibit phosphate transport in OK cells can he found in extracts from OOM tumors. It remains uncertain, however, whether these are related to the long-sought phosphaturic factor responsible for the phosphate wasting seen in OOM patients. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. Hyogo Chuo Hosp, Natl Sanatorium, Sanda 6691515, Japan. Kobe Univ, Sch Med, Dept Med, Chuo Ku, Kobe, Hyogo 650, Japan. Kuyunghee Univ, Dept Internal Med, Seoul, South Korea. Univ Jena, Innere Med Klin, D-6900 Jena, Germany. Univ Uppsala, Dept Med Sci, S-75185 Uppsala, Sweden. RP Jonsson, KB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, 50 Blossom St,WEL 501, Boston, MA 02114 USA. NR 30 TC 24 Z9 24 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUN PY 2001 VL 169 IS 3 BP 613 EP 620 DI 10.1677/joe.0.1690613 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 440TT UT WOS:000169190900022 PM 11375132 ER PT J AU Chiao, CC Hanlon, RT AF Chiao, CC Hanlon, RT TI Cuttlefish camouflage: Visual perception of size, contrast and number of white squares on artificial checkerboard substrata initiates disruptive coloration SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE camouflage; visual perception; sensory; colour patterns; disruptive coloration; cuttlefish; Sepia pharaonis AB We investigated some visual background features that influence young cuttlefish, Sepia pharaonis, to change their skin patterning from 'general resemblance' of the substratum to disruptive coloration that breaks up their body form. Using computer-generated black/white checkerboard patterns as substrata, we first found that the size of the white squares had to be within a certain narrow range (relative to the size of the cuttlefish 'white square') for the animal to exhibit disruptive skin patterning. Second, given the appropriate size of checker, cuttlefish regulated their disruptive skin patterns according to the contrast between white and black squares, Third, by manipulating the number of white squares on a black background, we found that as few as four white squares among 316 black squares (or 1.25 %) produced disruptive patterning, yet increasing the number of white squares to 20, 40 or 80 did not increase the frequency of appearance of the cuttlefish 'white square', but only its clarity of expression, These results demonstrate that the size, contrast and number of white objects in the surrounding substratum influence the production and expression of disruptive skin patterns in young cuttlefish. C1 Marine Biol Lab, Marine Resources Ctr, Woods Hole, MA 02543 USA. RP Chiao, CC (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. RI Hanlon, Roger/Q-8687-2016 OI Hanlon, Roger/0000-0003-0004-5674 NR 18 TC 74 Z9 74 U1 1 U2 47 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 J9 J EXP BIOL JI J. Exp. Biol. PD JUN PY 2001 VL 204 IS 12 BP 2119 EP 2125 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 451KH UT WOS:000169800900008 PM 11441053 ER PT J AU Stone, VE Mansourati, FF Poses, RM Mayer, KH AF Stone, VE Mansourati, FF Poses, RM Mayer, KH TI Relation of physician specialty and HIV/AIDS experience to choice of guideline-recommended antiretroviral therapy SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE HIV/AIDS; physician specialty; antiretroviral therapy ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PNEUMOCYSTIS-CARINII PNEUMONIA; ACUTE MYOCARDIAL-INFARCTION; PRIMARY-CARE PHYSICIANS; HIV-INFECTED PERSONS; SOCIETY USA PANEL; VIRUS INFECTION; UPDATED RECOMMENDATIONS; HEART-FAILURE; DRUG-THERAPY AB Background: Controversy exists regarding who should provide care for those with HIV/AIDS. While previous studies have found an association between physician HIV experience and patient outcomes, less is known about the relationship of physician specialty to HIV/AIDS outcomes or quality of care. Objective: To examine the relationship between choice of appropriate antiretroviral therapy (ART) to physician specialty and HIV/AIDS experience. Design: Self-administered physician survey. Participants: Random sample of 2,478 internal medicine (IM) and infectious disease (ID) physicians. Measurements: Choice of guideline-recommended ART. Results: Two patients with HIV disease, differing only by CD4+ count and HIV RNA load, were presented, Respondents were asked whether ART was indicated, and if so, what ART regimen they would choose. Respondents' ART choices were categorized as "recommended" or not by Department of Health and Human Services guidelines. Respondents' HIV/AIDS experience was categorized as moderate to high (MOD/HI) or none to low (NO/LO). For Case 1, 72.9% of responding physicians chose recommended ART. Recommended ART was more Likely (P<.01) to be chosen by ID physicians (88.2%) than by IM physicians (57.1%). Physicians with MOD/HI experience were also more likely (P <.01) to choose recommended ART than those with NO/LO experience. Finally, choice of ART was examined using logistic regression: specialty and HIV experience were found to be independent predictors of choosing recommended ART (for ID physicians, odds ratio [OR], 4.66; 95% confidence interval [95% CI], 3.15 to 6.90; and for MOD/HI experience, OR, 2.05; 95% CI, 1.33 to 3.16). Results for Case 2 were similar. When the analysis was repeated excluding physicians who indicated they would refer the HIV "patient," specialty and HIV experience were not significant predictors of choosing recommended ART. Conclusions: Guideline-recommended ART appears to be less likely to be chosen by generalists and physicians with less HIV/AIDS experience, although many of these physicians report they would refer these patients in clinical practice. These results lend support to current recommendations for routine expert consultant input in the management of those with HIV/AIDS. C1 Brown Univ, Mem Hosp Rhode Isl, Dept Med, Div Gen Internal Med, Providence, RI 02912 USA. Brown Univ, Mem Hosp Rhode Isl, Dept Med, Div Infect Dis, Providence, RI 02912 USA. RP Stone, VE (reprint author), Massachusetts Gen Hosp, Gen Med Unit, 50 Staniford St,9th Flr, Boston, MA 02114 USA. NR 37 TC 50 Z9 51 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2001 VL 16 IS 6 BP 360 EP 368 DI 10.1046/j.1525-1497.2001.016006360.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 443QE UT WOS:000169351200002 PM 11422632 ER PT J AU Nelson, K Cunningham, W Andersen, R Harrison, G Gelberg, L AF Nelson, K Cunningham, W Andersen, R Harrison, G Gelberg, L TI Is food insufficiency associated with health status and health care utilization among adults with diabetes? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE food insufficiency; diabetes; health status ID SELF-RATED HEALTH; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; UNITED-STATES; HOSPITALIZED-PATIENTS; SOCIOECONOMIC-STATUS; MEDICAL-CARE; HUNGER; POPULATION; MALNUTRITION AB Objectives: Preliminary studies have shown that among adults with diabetes, food insufficiency has adverse health consequences, including hypoglycemic episodes and increased need for health care services. The purpose of this study was to determine the prevalence of food insufficiency and to describe the association of food insufficiency with health status and health care utilization in a national sample of adults with diabetes. Methods: We analyzed data from adults with diabetes (n = 1,503) interviewed in the Third National Health and Nutrition Examination Survey. Bivariate and multivariate analyses were used to examine the relationship of food insufficiency to self-reported health status and health care utilization. Results: Six percent of adults with diabetes reported food insufficiency, representing more than 568,600 persons nationally (95% confidence interval, 368,400 to 768,800). Food insufficiency was more common among those with incomes below the federal poverty level (17% vs 4%, P less than or equal to .001). Adults with diabetes who were food insufficient were more likely to report fair or poor health status than those who were not (63% vs 43%; odds ratio, 2.2; P =.05). In a multivariate analysis, fair or poor health status was independently associated with poverty, nonwhite race, low educational achievement, and number of chronic diseases, but not with food insufficiency. Diabetic adults who were food insufficient reported more physician encounters, either in clinic or by phone, than those who were food secure (12 vs 7, P <.05). In a multivariate linear regression, food insufficiency remained independently associated with increased physician utilization among adults with diabetes. There was no association between food insufficiency and hospitalization in bivariate analysis. Conclusions: Food insufficiency is relatively common among low-income adults with diabetes and was associated with higher physician utilization. C1 Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Community Hlth Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Family Med, Los Angeles, CA USA. RP Nelson, K (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, 1660 S Columbian Wy, Seattle, WA 98108 USA. NR 66 TC 48 Z9 53 U1 2 U2 8 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2001 VL 16 IS 6 BP 404 EP 411 DI 10.1046/j.1525-1497.2001.016006404.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 443QE UT WOS:000169351200008 PM 11422638 ER PT J AU Cooper, DKC AF Cooper, DKC TI Christiaan Barnard and his contributions to heart transplantation SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Review ID BRAIN-DEATH; CARDIAC TRANSPLANTATION; HYPOTHERMIC PERFUSION; DONOR HEART; THERAPY; STORAGE; BYPASS AB Christiaan (Chris) Barnard was born in South Africa in 1922 and qualified in medicine at the University of Cape Town in 1946. Following surgical training in Cape Town and Minneapolis, Barnard established a successful open heart surgery program at Groote Schuur Hospital. In 1967, he led the team that performed the world's first human-to-human heart transplant. Although his first patient survived only 18 days, 4 of his first 10 patients survived for more than 1 year, 2 living for 13 and 23 years, respectively. With his junior colleague, Jaques Losman, Barnard then developed the operation of heterotopic heart transplantation. In 1981, his group was the first to successfully transport donor hearts using a hypothermic perfusion storage device. Several studies on the hemodynamic and metabolic sequelae of brain death were carried out in his department. Barnard retired from the University of Cape Town in 1983 at the age of 61. Now in his 79th year, he continues to pursue his interest in writing for the public. In the words of one of his former colleagues, he is a "surgical visionary and simply the most unforgettable character of the second generation of cardiac surgeons." C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH East,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 26 TC 9 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD JUN PY 2001 VL 20 IS 6 BP 599 EP 610 DI 10.1016/S1053-2498(00)00245-X PG 12 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 441PW UT WOS:000169239600001 PM 11404164 ER PT J AU Maatta, M Virtanen, I Burgeson, R Autio-Harmainen, H AF Maatta, M Virtanen, I Burgeson, R Autio-Harmainen, H TI Comparative analysis of the distribution of laminin chains in the basement membranes in some malignant epithelial tumors: The alpha 1 chain of laminin shows a selected expression pattern in human carcinomas SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE carcinoma; invasion; laminin; immunohistochemistry ID IN-SITU HYBRIDIZATION; A-CHAIN; RESTRICTED DISTRIBUTION; CELL-MIGRATION; GAMMA-2 CHAIN; CHROMOSOMAL ASSIGNMENT; MONOCLONAL-ANTIBODIES; LARYNGEAL CARCINOMAS; GASTRIC-CARCINOMA; LUNG-CARCINOMA AB Laminins (Ln), together with Type IV collagen and nidogen-l, form the structural integrity of the basement membranes (BM). In this study we used immunohistochemistry to show the distribution of laminin chains alpha1, alpha3, alpha5, beta1, beta2, beta3, gamma1, gamma2, as well as Type IV collagen, in various types of carcinomas and in normal tissues. Except for diffuse gastric carcinomas and infiltrative breast carcinomas, the malignant epithelial tumor clusters were surrounded by quite a continuous BM in most tumors. These BMs comprised most abundantly Ln alpha5, beta1, and gamma1 chains. Conversely, the Ln alpha1 chain, a component of laminins-1 and -3, showed the most restricted distribution in BMs of both normal tissues and malignancies, being moderately present in carcinomas of thyroid gland and ovary and in intraductal carcinomas of breast. In other types of carcinomas, immunoreactivity for Ln oil chain was found more randomly and was practically negative in carcinomas of tongue, stomach, and colon. These findings were comparable to those observed by in situ hybridization, which showed that carcinomas of thyroid gland and intraductal carcinomas of breast constitutively expressed Ln alpha1 mRNA and that the epithelial tumor cells were the main producers of it. The results suggest that epithelial malignancies, except for infiltrative breast and diffuse gastric carcinomas, produce more notable amounts of BM macromolecules in their growth substratum than has previously been anticipated. Corroborating their widespread distribution in normal epithelial tissues, the chains of Lns-5 and -10 are the most abundant Ln molecules in the corresponding carcinomas. C1 Univ Oulu, Dept Pathol, Oulu 90014, Finland. Univ Helsinki, Dept Anat, Inst Biomed, Helsinki, Finland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Maatta, M (reprint author), Univ Oulu, Dept Pathol, POB 5000,Aapistie 5, Oulu 90014, Finland. NR 56 TC 61 Z9 65 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUN PY 2001 VL 49 IS 6 BP 711 EP 725 PG 15 WC Cell Biology SC Cell Biology GA 441MC UT WOS:000169233300005 PM 11373318 ER PT J AU Brander, C Matter-Reissmann, UB Jones, NG Walker, BD Sachs, DH Seebach, JD AF Brander, C Matter-Reissmann, UB Jones, NG Walker, BD Sachs, DH Seebach, JD TI Inhibition of human NK cell-mediated cytotoxicity by exposure to ammonium chloride SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE human; NK cells; CTL; cytotoxicity; xenotransplantation ID NATURAL-KILLER-CELLS; LYSOSOMAL-ENZYMES; CONCANAMYCIN-A; PLASMA-CELLS; PERFORIN; PATHWAYS; CHLOROQUINE; TARGET; HETEROGENEITY; BIOSYNTHESIS AB Ammonium-chloride-containing solutions (AC) are routinely used to lyse red blood cells during preparation of PBMC. Although exposure to AC has been described to affect the ultrastructural appearance of large granular lymphocytes and to temporarily inhibit cytolytic activity of PBMC preparations, the cellular basis of this phenomenon has not been studied. Hen, the inhibitory effect of BC. on human CTL and NK-mediated cytotoxicity has been analyzed in 4-h Cr-51-release assays. The results show that NIC killing of K562 leukemia cells and xenogeneic endothelial cells is inhibited by AC exposure. The effect is dose-dependent and reversible, because recovery of cytotoxicity is observed within 15 h of re-culturing. AC dues not reduce the viability of NK cells and the inhibitory effect is not mediated by the exhaustive release of granzymes upon AC treatment. In contrast, antigen-specific CTL. killing of EBV-transformed B-lymphoblastoid cell lines and xenogeneic PHA lymphoblasts was less sensitive to AC and data are presented suggesting that Fast-induced apoptosis is not inhibited by AC, In conclusion, perforin-mediated NK killing is AC-sensitive whereas CTL killing and Fast-mediated killing appear to be AC-resistant. Therefore, AC represents a powerful tool to study different mechanisms of cell-mediated cytotoxicity and may be helpful in assessing antigen-specific CTL cytotoxicity without the influence of NK cell-mediated background killing. (C) 2001 Elsevier science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, AIDS Res Ctr, Boston, MA 02129 USA. Univ Zurich Hosp, Dept Internal Med, Lab Transplantat Immunol, CH-8091 Zurich, Switzerland. RP Seebach, JD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL63430]; NIAID NIH HHS [5P01 AI39755] NR 52 TC 8 Z9 8 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 1 PY 2001 VL 252 IS 1-2 BP 1 EP 14 DI 10.1016/S0022-1759(01)00326-X PG 14 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 428KF UT WOS:000168460300001 PM 11334960 ER PT J AU Su, M He, CF West, CA Mentzer, SJ AF Su, M He, CF West, CA Mentzer, SJ TI Cytolytic peptides induce biphasic permeability changes in mammalian cell membranes SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE cytolysis; melittin; gramicidin; vital dyes; calcein; trypan blue ID CYTO-TOXICITY; TRYPAN BLUE; MELITTIN; CARBOXYFLUORESCEIN; FLUORESCENCE; RELEASE; ASSAY; RETENTION; MOLECULE; LINE AB The cytolytic peptides melittin and gramicidin S are naturally occurring agents that provide a comparative model for studies of complement, immunotoxin and cell-mediated membrane permeability. Most attempts to characterize cytolytic peptides have used model membrane systems including phospholipid vesicles or erythrocytes. Membrane vesicles permit the use of self-quenching concentrations of fluorescent permeability markers. while erythrocytes release measurable hemoglobin. Attempts at measuring early membrane permeability changes in nucleated mammalian cells have been limited. To measure the kinetics of mammalian cell membrane permeability changes induced by cytolytic peptides, we developed a 96-well fluorescence cytolysis assay using the cytoplasmic fluorescent dye calcein as the membrane permeability marker. To facilitate rapid assessment of membrane permeability, trypan blue was added to the assay solution to quench (a) released fluorescence and (b) retained intracellular fluorescence. Trypan blue also provided a complementary visual assessment of cell viability. Using this assay, a detailed kinetic analysis demonstrated permeability of the cell membranes within seconds of exposure to the cytolytic peptides. The rapid permeabilization of the cell membranes was confirmed by flow cytometry using the calcium indicator dye fluo-3, The assay also demonstrated a second slower phase of marker release over the next several hours. The fluorescence cytolysis assay was able to reliably detect the biphasic permeability changes associated with the melittin and gramicidin S peptides suggesting the potential utility of this assay in the assessment of other cytolytic agents. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Dana Farber Canc Inst, Immunophysiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Surg Res Labs, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Dana Farber Canc Inst, Immunophysiol Lab, Room G09,JFB,44 Binney St, Boston, MA 02115 USA. NR 30 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 1 PY 2001 VL 252 IS 1-2 BP 63 EP 71 DI 10.1016/S0022-1759(01)00334-9 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 428KF UT WOS:000168460300007 PM 11334966 ER PT J AU Pertl, U Luster, AD Varki, NM Homann, D Gaedicke, G Reisfeld, RA Lode, HN AF Pertl, U Luster, AD Varki, NM Homann, D Gaedicke, G Reisfeld, RA Lode, HN TI IFN-gamma-inducible protein-10 is essential for the generation of a protective tumor-specific CD8 T cell response induced by single-chain IL-12 gene therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID X-C CHEMOKINE; INTERFERON-GAMMA; IN-VIVO; CXC CHEMOKINES; MURINE NEUROBLASTOMA; ANTITUMOR-ACTIVITY; DENDRITIC CELLS; INTERLEUKIN-12; ANGIOGENESIS; IP-10 AB The successful induction of T cell-mediated protective immunity against poorly immunogenic malignancies remains a major challenge for cancer immunotherapy. Here, we demonstrate that the induction of tumor-protective immunity by IL-12 in a murine neuroblastoma model depends entirely on the CXC chemokine IFN-gamma -inducible protein 10 (IP-10). This was established by in vivo depletion of IP-10 with mAbs in mice vaccinated against NXS2 neuroblastoma by gene therapy with a linearized, single-chain (sc) version of the heterodimeric cytokine IL-12 (scIL-12). The efficacy of IP-10 depletion was indicated by the effective abrogation of scIL-12-mediated antiangiogenesis and T cell chemotaxis in mice receiving s.c. injections of scIL-12-producing NXS2 cells. These findings were extended by data demonstrating that IP-10 is directly involved in the generation of a tumor-protective CD8(+) T cell-mediated immune response during the early immunization phase. Four lines of evidence support this contention: First, A/J mice vaccinated with NXS2 scIL-12 and depleted of IP-10 by, two different anti-IP-10 mAbs revealed an abrogation of systemic-protective immunity against disseminated metastases. Second, CD8(+) T cell-mediated MHC class I Ag-restricted tumor cell lysis was inhibited in such mice. Third, intracellular IFN-gamma expressed by proliferating CD8(+) T cells was substantially inhibited in IP-10-depleted, scIL-12 NXS2-vaccinated mice. Fourth, systemic tumor protective Immunity was completely abrogated in mice depleted of IP-10 in the early immunization phase, but not if IP-10 was depleted only in the effector phase. These findings suggest that IP-10 plays a crucial role during the early immunization phase in the induction of immunity against neuroblastoma by scIL-12 gene therapy. C1 Charite Childrens Hosp, D-13353 Berlin, Germany. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis,Div Rheumatol Alle, Charlestown, MA 02129 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. RP Lode, HN (reprint author), Charite Childrens Hosp, Augustenburgerpl 1, D-13353 Berlin, Germany. FU NCI NIH HHS [CA69212, CA83140] NR 41 TC 86 Z9 93 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2001 VL 166 IS 11 BP 6944 EP 6951 PG 8 WC Immunology SC Immunology GA 471VG UT WOS:000170948900061 PM 11359856 ER PT J AU Mangano, A Gonzalez, E Dhanda, R Catano, G Bamshad, M Bock, A Duggirala, R Williams, K Mummidi, S Clark, RA Ahuja, SS Dolan, MJ Bologna, R Sen, L Ahuja, SK AF Mangano, A Gonzalez, E Dhanda, R Catano, G Bamshad, M Bock, A Duggirala, R Williams, K Mummidi, S Clark, RA Ahuja, SS Dolan, MJ Bologna, R Sen, L Ahuja, SK TI Concordance between the CC chemokine receptor 5 genetic determinants that alter risks of transmission and disease progression in children exposed perinatally to human immunodeficiency virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PEDIATRIC HIV-1 INFECTION; PLASMA VIRAL LOAD; CELL-SURFACE CCR5; VERTICAL TRANSMISSION; RHEUMATOID-ARTHRITIS; TYPE-1 TRANSMISSION; AIDS PROGRESSION; DENDRITIC CELLS; NATURAL-HISTORY; CLINICAL COURSE AB If CC chemokine receptor 5 (CCR5)-dependent mechanisms at the time of initial virus exposure are important determinants of virus entry and disease outcome, then the polymorphisms in CCR5 that influence risk of transmission and disease progression should be similar; this hypothesis was tested in a cohort of 649 Argentinean children exposed perinatally to human immunodeficiency virus type 1 (HIV-1). Two lines of evidence support this hypothesis. First, CCR5 haplotype pairs associated with enhanced risk of transmission were the chief predictors of a faster disease course. Second, some of the haplotype pairs associated with altered rates of transmission and disease progression in children were similar to those that we previously found influenced outcome in European American adults. This concordance suggests that CCR5 haplotypes may serve as genetic rheostats that influence events occurring shortly after initial virus exposure, dictating not only virus entry but, by extension, also the extent of early viral replication. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. Hosp Pediat JP Garrahan, Lab Biol Celular & Retrovirus, Buenos Aires, DF, Argentina. Hosp Pediat JP Garrahan, Serv Infectol, Buenos Aires, DF, Argentina. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Div Infect Dis, San Antonio, TX USA. Wilford Hall USAF Med Ctr, Dept Med, Infect Dis Serv, Lackland AFB, TX 78236 USA. Purdue Pharma, Stamford, CT USA. Univ Utah, Eccles Inst Human Genet, Dept Pediat, Salt Lake City, UT USA. RP Ahuja, SK (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr,Mail Code 7880, San Antonio, TX 78229 USA. RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 FU NIAID NIH HHS [AI-43279, AI-4632] NR 85 TC 67 Z9 67 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 1 PY 2001 VL 183 IS 11 BP 1574 EP 1585 DI 10.1086/320705 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 430XZ UT WOS:000168601900004 PM 11335892 ER PT J AU Tian, WD Gillies, R Brancaleon, L Kollias, N AF Tian, WD Gillies, R Brancaleon, L Kollias, N TI Aging and effects of ultraviolet A exposure may be quantified by fluorescence excitation spectroscopy in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE photoageing; skin fluorescence ID MELANOGENESIS ACTION SPECTRA; COLLAGEN CROSS-LINKING; HUMAN-SKIN; REACTION-PRODUCTS; THYMINE DIMERS; IN-VIVO; WAVELENGTH; DEPENDENCE; GLYCATION; OXIDATION AB The fluorescence properties of skin chromophores such as tryptophan and collagen cross-links might be useful markers of aging and photoaging. As the fluorescence of pepsin-digestible collagen cross-links was found to increase with aging and decrease with photoaging we investigated the characteristics of this dependence. In vivo fluorescence excitation spectra (emission at 380 nm) of SKH hairless mouse model skin are characterized by two bands centered near 295 nm and 335 nm due, respectively, to epidermal tryptophan moieties and pepsin-digestible collagen cross-links, Several groups of hairless mice were followed over a period of 18 mo to document changes in skin fluorescence with aging. Other groups of animals were exposed to either broad band or narrowband ultraviolet A radiation to determine the effects of ultraviolet A exposure on the fluorescence of the dermal collagen cross-links and to determine an action spectrum for the induced changes. We also found that the intensity of pepsin-digestible collagen cross-links in vivo increases linearly with age and that the fluorescence of epidermal tryptophan decreases linearly with age. We found that the fluorescence of pepsin-digestible collagen cross-links decreases immediately following exposure to ultraviolet A whereas epidermal tryptophan fluorescence increases. Both changes were dose dependent but the increase in tryptophan fluorescence occurred exclusively in young animals (2-6 mo old). We found that the ultraviolet-induced fluorescence decrease of pepsin-digestible collagen cross-links is wavelength specific. The action spectrum for the ultraviolet A effect on the in vivo fluorescence of pepsin-digestible collagen cross-links shows a distinct maximum at 335 nm that corresponds to the maximum in the fluorescence excitation spectrum due to pepsin-digestible collagen cross-links. Our results seem to indicate that in vivo fluorescence of epidermal tryptophan moieties and collagen cross-links in the dermal matrix may serve as markers for skin aging, for photoaging, and for immediate assessment of exposure to ultraviolet A radiation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Brancaleon, L (reprint author), Ninewells Hosp, Dept Dermatol & Photobiol Unit, Dundee DD1 9SY, Scotland. RI Brancaleon, Lorenzo/B-5625-2009 NR 36 TC 24 Z9 25 U1 0 U2 3 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 JUN PY 2001 VL 116 IS 6 BP 840 EP 845 DI 10.1046/j.1523-1747.2001.01361.x PG 6 WC Dermatology SC Dermatology GA 443QA UT WOS:000169350800002 PM 11407969 ER PT J AU Huzaira, M Rius, F Rajadhyaksha, M Anderson, RR Gonzalez, S AF Huzaira, M Rius, F Rajadhyaksha, M Anderson, RR Gonzalez, S TI Topographic variations in normal skin, as viewed by in vivo reflectance confocal microscopy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE aging; dermis; stratum corneum ID SCANNING LASER MICROSCOPY; HUMAN STRATUM-CORNEUM; IN-VIVO; HUMAN-EPIDERMIS; REGIONAL DIFFERENCES; ROUTINE HISTOLOGY; TIME; THICKNESS; CONTRAST AB Near-infrared confocal microscopy is a new tool that provides skin images in vivo, with high resolution and contrast at a specific depth. Regional variations in live human skin viewed by confocal microscope have not been studied so far. In vivo reflectance confocal microscopy was performed in 10 adults (eight males, two females) of various skin phototypes. Six topographic sites were studied in each subject: forehead, cheek, inner and outer forearm surfaces, lower back and leg. Epidermal thickness at suprapapillary epidermal plates and rete pegs was measured during real-time imaging and the number and diameter of epidermal keratinocytes in each epidermal cell layer as well as the characteristics of dermal papillae were defined from the grabbed images. Stratum corneum appeared brighter in sun-exposed than in sun-protected areas and particularly pronounced in heavily pigmented individuals. The epidermal thickness at rete pegs, but not the suprapapillary epidermal plate, was greater in sun-exposed areas than in sun-protected sites except forearm flexor surface. The en face numerical density of granular keratinocytes is greater on the face as compared with all other sites, whereas the surface density of spinous keratinocytes is greater on sun-protected sites. Additionally, the number of basal keratinocytes per millimeter length of dermoepidermal junction is greater in sun exposed areas. Interestingly, the dermal papillae shape varies and their sizes increase in circumference from sun-exposed to sun-protected sites, as observed at a specific depth below the stratum corneum, In summary, our results demonstrate that near infra-red reflectance confocal microscopy is a feasible tool for microscopic analysis of skin morphometry in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Univ Malaga, Fac Med, Dept Prevent Med & Publ Hlth, E-29071 Malaga, Spain. Lucid Inc, Henrietta, NY USA. RP Gonzalez, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, 40 Blossom St,Bartlett Hall 814, Boston, MA 02114 USA. NR 30 TC 144 Z9 153 U1 2 U2 13 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 JUN PY 2001 VL 116 IS 6 BP 846 EP 852 DI 10.1046/j.0022-202x.2001.01337.x PG 7 WC Dermatology SC Dermatology GA 443QA UT WOS:000169350800003 PM 11407970 ER PT J AU Read, J Pearce, J Li, XC Muirhead, H Chirgwin, J Davies, C AF Read, J Pearce, J Li, XC Muirhead, H Chirgwin, J Davies, C TI The Crystal Structure of Human Phosphoglucose Isomerase at 1.6 angstrom resolution: Implications for catalytic mechanism, cytokine activity and haemolytic anaemia SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE aldose-ketose isomerases; neuroleukin; cytokine; haemolytic anaemia; X-ray crystallography ID GLUCOSE PHOSPHATE ISOMERASE; AUTOCRINE MOTILITY FACTOR; HEMOLYTIC-ANEMIA; GLUCOSE-6-PHOSPHATE ISOMERASE; GLUCOSEPHOSPHATE ISOMERASE; TRIOSEPHOSPHATE ISOMERASE; PHOSPHOHEXOSE ISOMERASE; NEUROTROPHIC FACTOR; FACTOR NEUROLEUKIN; MOLECULAR-CLONING AB Phosphoglucose isomerase (PGI) is a multifunctional protein, which, inside the cell, functions as a housekeeping enzyme of glycolysis and gluconeogenesis and, outside the cell, exerts wholly unrelated cytokine properties. We have determined the structure of human PGI to a resolution of 1.6 Angstrom using X-ray crystallography. The structure is highly similar to other PGIs, especially the architecture of the active site. Fortuitous binding of a sulphate molecule from the crystallisation solution has facilitated an accurate description of the substrate phosphate-binding site. Comparison with both native and inhibitor-bound rabbit PCI structures shows that two loops move closer to the active site upon binding inhibitor. Interestingly, the human structure most closely resembles the inhibitor-bound structure, suggesting that binding of the phosphate moiety of the substrate may trigger this conformational change. We suggest a new mechanism for catalysis that uses Glu357 as the base catalyst for the isomerase reaction rather than His388 as proposed previously. The human PGI structure has also provided a detailed framework with which to map mutations associated with non-spherocytic haemolytic anaemia. (C) 2001 Academic Press. C1 Univ Sussex, Sch Biol Sci, Brighton BN1 9QG, E Sussex, England. Univ Bristol, Sch Med Sci, Bristol BS8 1TD, Avon, England. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Vet Adm Med Ctr, Res Serv, San Antonio, TX 78229 USA. RP Davies, C (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. NR 70 TC 70 Z9 72 U1 1 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 1 PY 2001 VL 309 IS 2 BP 447 EP 463 DI 10.1006/jmbi.2001.4680 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 442CB UT WOS:000169266700009 PM 11371164 ER PT J AU Allinquant, B Bertrand, E Brouillet, E Caille, I Bouillot, C Cole, GM Prochiantz, A AF Allinquant, B Bertrand, E Brouillet, E Caille, I Bouillot, C Cole, GM Prochiantz, A TI A short cytoplasmic domain of the amyloid precursor protein induces apoptosis in vitro and in vivo SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Ecole Normale Super, CNRS, UMR 8542, F-75230 Paris 05, France. VA Greater LA, GRECC 2E, Sepulveda, CA 91343 USA. RI Brouillet, Emmanuel/B-4784-2014 OI Brouillet, Emmanuel/0000-0001-6322-7403 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2001 VL 77 SU 1 MA P0120 BP 24 EP 24 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 441RL UT WOS:000169243300081 ER PT J AU Lu, XY Wyszynski, M Sheng, M Baudry, M AF Lu, XY Wyszynski, M Sheng, M Baudry, M TI Proteolysis of glutamate receptor-interacting protein by calpain in rat brain: implications for synaptic plasticity SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calpain; glutamate; GRIP; receptor; synaptic plasticity ID LONG-TERM POTENTIATION; CULTURED HIPPOCAMPAL SLICES; MEDIATED TRUNCATION; AMPA RECEPTORS; POSTSYNAPTIC MEMBRANE; IONOTROPIC RECEPTORS; AXOSPINOUS SYNAPSES; EXCITATORY SYNAPSES; ACID RECEPTORS; SPINE SYNAPSES AB Activation of the calcium-dependent protease calpain has been proposed to be a key step in synaptic plasticity in the hippocampus. However, the exact pathway through which calpain mediates or modulates changes in synaptic function remains to be clarified, Here we report that glutamate receptor-interacting protein (GRIP) is a substrate of calpain, as calpain-mediated GRIP degradation was demonstrated using three different approaches: (i) purified calpain I digestion of synaptic membranes, (ii) calcium treatment of frozen-thawed brain sections, and (iii) NMDA-stimulated organotypic hippocampal slice cultures. More importantly, calpain activation resulted in the disruption of GRIP binding to the GluR2 subunit of alpha -amino-3-hydroxy-5-methylisoxazole-4propionate (AMPA) receptors. Because GRIP has been proposed to function as an AMPA receptor-targeting and synaptic-stabilizing protein, as well as a synaptic-organizing molecule, calpain-mediated degradation of GRIP and disruption of AMPA receptor anchoring are likely to play important roles in the structural and functional reorganization accompanying synaptic modifications in long-term potentiation and long-term depression. C1 Univ So Calif, Program Neurosci, Los Angeles, CA 90089 USA. Massachusetts Gen Hosp, Dept Neurobiol, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Baudry, M (reprint author), Univ So Calif, Program Neurosci, HNB 124, Los Angeles, CA 90089 USA. FU NIA NIH HHS [AG-14751] NR 56 TC 43 Z9 45 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2001 VL 77 IS 6 BP 1553 EP 1560 DI 10.1046/j.1471-4159.2001.00359.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 444GU UT WOS:000169392400012 PM 11413238 ER PT J AU Taber, KH Murphy, DD Blurton-Jones, MM Hurley, RA AF Taber, KH Murphy, DD Blurton-Jones, MM Hurley, RA TI An update on estrogen: Higher cognitive function, receptor mapping, neurotrophic effects SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID MESSENGER-RNA EXPRESSION; DENDRITIC SPINE DENSITY; CEREBRAL BLOOD-FLOW; REPLACEMENT THERAPY; ALZHEIMERS-DISEASE; CHOLINE-ACETYLTRANSFERASE; ESTRADIOL INCREASES; GENDER DIFFERENCES; BRAIN INJURY; WOMEN C1 Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Baylor Coll Med, Dept Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Herbert J Frensley Ctr Imaging Res, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Psychiat Serv, Houston, TX USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Taber, KH (reprint author), Baylor Coll Med, Dept Radiol, 1 Baylor Plaza, Houston, TX 77030 USA. OI Blurton-Jones, Mathew/0000-0002-7770-7157 NR 41 TC 17 Z9 18 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 2001 VL 13 IS 3 BP 313 EP 317 DI 10.1176/appi.neuropsych.13.3.313 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 462RP UT WOS:000170433800001 PM 11514636 ER PT J AU Mendez, MF Lipton, A AF Mendez, MF Lipton, A TI Emergent neuroleptic hypersensitivity as a herald of presenile dementia SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID FRONTOTEMPORAL DEMENTIA; LEWY BODIES; PARKINSONS-DISEASE; CLINICAL CHARACTERISTICS; FAMILIAL AGGREGATION; ALZHEIMERS-DISEASE; SENSITIVITY; FTDP-17; CHROMOSOME-17; MUTATION AB Neuroleptic hypersensitivity is characteristic of dementia with Lewy bodies (DLB) but not Of other dementias. The authors report 5 patients with psychotic mood disorders and long-standing antipsychotic drug therapy. As they reached 50 to 60 years of age, they unexpectedly developed hypersensitivity to these medications, with rigidity, muteness, or the neuroleptic malignant syndrome. Nearly coincident with this reaction, they developed progressive cognitive deficits consistent with frontotemporal dementia. These patients illustrate emergent neuroleptic hypersensitivity as an early manifestation of other dementias. The predisposition to neuroleptic hypersensitivity could result from depleted nigral dopaminergic neurons suggested by "smudging" of the substantia nigra pars compacta on magnetic resonance imaging. C1 W Los Angeles VA Med Ctr, Neurobehav Unit, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Biobehav Sci, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), W Los Angeles VA Med Ctr, Neurobehav Unit, Psychiat Serv, 691 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 32 TC 8 Z9 9 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 2001 VL 13 IS 3 BP 347 EP 356 DI 10.1176/appi.neuropsych.13.3.347 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 462RP UT WOS:000170433800006 PM 11514641 ER PT J AU Hsueh, YP Roberts, AM Volta, M Sheng, M Roberts, RG AF Hsueh, YP Roberts, AM Volta, M Sheng, M Roberts, RG TI Bipartite interaction between neurofibromatosis type I protein (neurofibromin) and syndecan transmembrane heparan sulfate proteoglycans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NF1; RasGAP; postsynaptic density; axon; yeast two-hybrid analysis; CASK/LIN-2 ID EPITHELIAL-CELLS; BASOLATERAL MEMBRANE; LOCALIZATION; CASK/LIN-2; NEURONS; GENE; NF1; DROSOPHILA; ACTIVATION; EXPRESSION AB The neurofibromatosis type 1 (NF1) gene encodes a large tumor suppressor protein (neurofibromin). Although it is known to possess Ras GTPase-activating protein (GAP) activity, the cellular role of neurofibromin remains unclear. Here we used yeast two-hybrid screening to identify neurofibromin-interacting proteins. Syndecan-2, a transmembrane heparan sulfate proteoglycan (HSPG), was isolated as a binding partner for two distinct regions of the neurofibromin protein. We subsequently found that neurofibromin can bind all four mammalian syndecans. NF1 interaction requires the transmembrane domain and a membrane-proximal region of the cytoplasmic tail of syndecan, but not the C terminus of syndecan known to bind to CASK, a membrane-associated guanylate kinase (MAGUK). Neurofibromin, syndecans, and CASK have overlapping subcellular distributions in axons and synapses of neurons, as shown by biochemical fractionation and immunostaining. Moreover, neurofibromin exists in a complex with syndecan and CASK in vivo, as evidenced by their coimmunoprecipitation from rat brain. Our findings suggest that interaction with different members of the syndecan family may be a mechanism for localizing neurofibromin to specialized domains of the plasma membrane. C1 Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Guys Kings & St Thomas Med Sch, Div Med & Mol Genet, London SE1 9RT, England. RP Sheng, M (reprint author), Acad Sinica, Inst Mol Biol, Taipei 115, Taiwan. RI Roberts, Roland/C-3596-2009; Volta, Manuela/D-2147-2012; OI Volta, Manuela/0000-0001-8468-0346; Roberts, Roland/0000-0001-6636-1579; Hsueh, Yi-Ping/0000-0002-0866-6275 NR 29 TC 50 Z9 52 U1 0 U2 3 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 JUN 1 PY 2001 VL 21 IS 11 BP 3764 EP 3770 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 436VY UT WOS:000168957600011 PM 11356864 ER PT J AU Rao, VLR Bowen, KK Rao, AM Dempsey, RJ AF Rao, VLR Bowen, KK Rao, AM Dempsey, RJ TI Up-regulation of the peripheral-type benzodiazepine receptor expression and [H-3]PK11195 binding in gerbil hippocampus after transient forebrain ischemia SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE forebrain ischemia; immunohistochemistry; mRNA; RT-PCR; mitochondrial benzodiazepine receptor; PK11195 binding ID TUMOR-NECROSIS-FACTOR; RAT-BRAIN; GLOBAL-ISCHEMIA; PK11195 BINDING; NEURONAL DEATH; MESSENGER-RNA; FACTOR-ALPHA; H-3 PK11195; SITES; LIGAND AB In mammalian CNS, the peripheral-type benzodiazepine receptor (PTBR) is localized on the outer mitochondrial membrane within the astrocytes and microglia. The main function of PTBR is to transport cholesterol across the mitochondrial membrane to the site of neurosteroid biosynthesis. The present study evaluated the changes in the PTBR density, gene expression and immunoreactivity in gerbil hippocampus as a function of reperfusion time after transient forebrain ischemia, Between 3 to 7 days of reperfusion, there was a significant increase in the maximal binding site density (B-max) of the PTBR antagonist [H-3]PK11195 (by 94-156%; P < 0.01) and PTBR mRNA levels (by 1.8- to 2.9-fold; P < 0.01). At 7 days of reperfusion, in the hippocampal CA1 (the brain region manifesting selective neuronal death), PTBR immunoreactivity increased significantly. Increased PTBR expression after transient forebrain ischemia may lead to increased neurosteroid biosynthesis, and thus may play a role in the ischemic pathophysiology, (C) 2001 Wiley-Liss, Inc. C1 Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA. Univ Wisconsin, Cardiovasc Res Ctr, Madison, WI 53792 USA. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Rao, VLR (reprint author), Univ Wisconsin, Dept Neurol Surg, F4-309 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA. FU NINDS NIH HHS [NS31220, NS28000] NR 52 TC 30 Z9 31 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 1 PY 2001 VL 64 IS 5 BP 493 EP 500 DI 10.1002/jnr.1101 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 438AZ UT WOS:000169032700007 PM 11391704 ER PT J AU Cariani, P AF Cariani, P TI Temporal codes, timing nets, and music perception SO JOURNAL OF NEW MUSIC RESEARCH LA English DT Review ID COMPLEX TONES; AUDITORY-SYSTEM; PITCH PERCEPTION; VIRTUAL PITCH; PHASE SENSITIVITY; OCTAVE TEMPLATES; COMPUTER-MODEL; TIME; PERIODICITY; MEMORY AB Temporal codes and neural temporal processing architectures (neural timing nets) that potentially subserve perception of pitch and rhythm are discussed. We address 1) propel-ties of neural interspike interval representations that may underlie basic aspects of musical tonality (e.g., octave similarities), 2) implementation of pattern-similarity comparisons between interval representations using feedforward timing nets, and 3) representation of rhythmic patterns in recurrent timing nets. Computer simulated interval-patterns produced by harmonic complex tones whose fundamentals are related through simple ratios showed higher correlations than for more complex ratios. Similarities between interval-patterns produced by notes and chords resemble similarity-judgements made by human listeners in probe tone studies. Feedforward timing nets extract common temporal patterns from their inputs, so as to extract common pitch irrespective of timbre and vice versa. Recurrent timing nets build up complex temporal expectations over time through repetition, providing a means of representing rhythmic patterns. They constitute alternatives to oscillators and clocks, with which they share many common functional properties. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. EM cariani@mac.com NR 122 TC 19 Z9 20 U1 1 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0929-8215 J9 J NEW MUSIC RES JI J. New Music Res. PD JUN PY 2001 VL 30 IS 2 SI SI BP 107 EP 135 DI 10.1076/jnmr.30.2.107.7115 PG 29 WC Computer Science, Interdisciplinary Applications; Music SC Computer Science; Music GA 541JH UT WOS:000174981100002 ER PT J AU Pittman, TJ O'Connor, MD Millar, S Erickson, JI AF Pittman, TJ O'Connor, MD Millar, S Erickson, JI TI Patient education - Designing a state-of-the-art consumer health information library SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID ACCESS C1 Massachusetts Gen Hosp, Patient & Family Learning Ctr, Boston, MA 02114 USA. RP Pittman, TJ (reprint author), Massachusetts Gen Hosp, Patient & Family Learning Ctr, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD JUN PY 2001 VL 31 IS 6 BP 316 EP 323 DI 10.1097/00005110-200106000-00010 PG 8 WC Nursing SC Nursing GA 443XE UT WOS:000169367600009 PM 11417171 ER PT J AU Christiani, DC Sharp, RR Collman, GW Suk, WA AF Christiani, DC Sharp, RR Collman, GW Suk, WA TI Applying genomic technologies in environmental health research: Challenges and opportunities SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID LUNG-CANCER; SOCIAL IMPLICATIONS; P53 MUTATIONS; SMOKING; GENES; PROJECT; SUSCEPTIBILITY; EXPOSURE; LEGAL; ADENOCARCINOMA AB Recent discoveries in molecular biology and genetics have made it possible for environmental health researchers to examine how genetic characteristics affect response to environmental exposures. Understanding such gene-environment interactions offers exciting possibilities for the prevention and control of environmentally induced diseases. Despite these potential benefits, the collection and analysis of genetic information in environmental health research presents many of the same ethical, legal, and social (ELSI) challenges found in other types of genetic research. In this article, we describe a number of ELSI challenges in environmental genomic research and the opportunities and responsibilities that accompany this research. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NIEHS, Off Sci Director, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Div Extramural Res, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Ctr Study Med Eth & Humanities, Durham, NC 27706 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES00002, ES05947] NR 45 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUN PY 2001 VL 43 IS 6 BP 526 EP 533 DI 10.1097/00043764-200106000-00003 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 440CT UT WOS:000169158900002 PM 11411324 ER PT J AU Todd, R Donoff, RB Kim, Y Wong, DTW AF Todd, R Donoff, RB Kim, Y Wong, DTW TI From the chromosome to DNA: Restriction fragment length polymorphism analysis and its clinical application SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DENTINOGENESIS-IMPERFECTA; FIELD CANCERIZATION; MOLECULAR-GENETICS; CANCER; LINKAGE; DEFECTS; GENES AB Understanding how chromosomal alterations contribute to acquired and inherited human disease requires the ability to manage the enormous physical and informational complexity of the deoxyribonucleic acid (DNA) packaged within. Important concepts and techniques involved in the analysis of DNA include restriction enzymes, Southern blotting, and restriction fragment length polymorphism/linkage analysis. These techniques have been essential in the understanding and diagnosis of several syndromes associated with the head and neck. The purpose of this article is to introduce DNA structure, describe some techniques fundamental to DNA analysis, and provide a brief overview of the clinical applications of this technology with respect to dentinogenesis imperfecta and oral field cancerization. (C) 2001 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Pathol, Boston, MA 02115 USA. RP Todd, R (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, 188 Longwood Ave, Boston, MA 02115 USA. NR 27 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUN PY 2001 VL 59 IS 6 BP 660 EP 667 DI 10.1053/joms.2001.22707 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 438AC UT WOS:000169030700015 PM 11381391 ER PT J AU Jones, GB Hynd, G Wright, JM Purohit, A Plourde, GW Huber, RS Mathews, JE Li, AW Kilgore, MW Bubley, GJ Yancisin, M Brown, MA AF Jones, GB Hynd, G Wright, JM Purohit, A Plourde, GW Huber, RS Mathews, JE Li, AW Kilgore, MW Bubley, GJ Yancisin, M Brown, MA TI Target-directed enediynes: Designed estramycins SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID HORMONE RECEPTOR SUPERFAMILY; HUMAN ESTROGEN-RECEPTOR; PROTEIN; BINDING; CHEMISTRY; COMPLEXES; AGENTS; ESTRADIOL; RADICALS; LIGANDS C1 Northeastern Univ, Dept Chem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Clemson Univ, GHS CU Biomed Cooperat, Clemson, SC 29634 USA. RP Jones, GB (reprint author), Northeastern Univ, Dept Chem, Boston, MA 02115 USA. OI Brown, Myles/0000-0002-8213-1658 FU NIGMS NIH HHS [R01 GM57123] NR 46 TC 54 Z9 55 U1 0 U2 1 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 JUN 1 PY 2001 VL 66 IS 11 BP 3688 EP 3695 DI 10.1021/jo0055842 PG 8 WC Chemistry, Organic SC Chemistry GA 435ZD UT WOS:000168911300006 PM 11374986 ER PT J AU Cornford, EM Cornford, ME Wright, EM Bruckner, DA Sampogna, S Hirayama, BA AF Cornford, EM Cornford, ME Wright, EM Bruckner, DA Sampogna, S Hirayama, BA TI Human cerebral cysticercosis: Immunolocalization of a sodium-dependent glucose cotransporter (SGLT) in larval and adult tapeworms SO JOURNAL OF PARASITOLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; MOLECULAR MIMICRY; IMMUNOHISTOCHEMICAL LOCALIZATION; HYMENOLEPIS-DIMINUTA; TRANSPORTER PROTEINS; RAT TAPEWORM; EXPRESSION; MEMBRANE; PARASITE; NEUROCYSTICERCOSIS AB Light microscopic immunocytochemistry was used to examine human brain cysticerci resected from the fourth ventricles of patients who had not been treated with anthelminthic drugs. Tissues were examined from 3 different patients undergoing surgery for treatment of hydrocephalus. A rabbit polyclonal antiserum to the peptide corresponding to amino acids 564-575 unique to the rabbit sodium-dependent, SGLT1 glucose cotransporter labeled with immunoperoxidase, localized immunoreactive SGLT epitopes. This antibody localizes SGLT1 in the apical brush borders of human enterocytes, but is negative in cytoplasm, as well as lateral and basal enterocyte membranes. Taenia solium neurocysticerci were SGLT positive; transporter protein was highly expressed on the surface microvilli of the external cyst wall. The well-developed network of small and larger osmoregulatory ducts within racemose larval cystcerci displayed high expression of SGLT cotransporter, consistent with a resorptive function for this system of tubules. Because water is cotransported with glucose molecules by the SGLT protein, its high expression in neurocysticerci may contribute to the expansive growth of these larvae in subarachnoid and intraventricular sites. The SGLT epitopes were also immunolocalized in gravid proglottids of Taenia saginata, indicating that cotransporter expression persisted in intestinal-dwelling, adult tapeworms. Cotransporter antibody was abundantly localized at the proglottid tegumentary surface and in the lateral osmoregulatory ducts, analogous to the SGLT localization in cysticerci. Furthermore, high expression of this cotransporter was seen in the branches of the uterus, suggesting that SGLT-mediated absorption of glucose and water has an important functional role within the reproductive system of adult tapeworms. C1 Univ Calif Los Angeles, Sch Med, Brain Res Inst, Dept Neurol, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, SW Reg VA Epilepsy Ctr, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Serv Neurol, SW Reg VA Epilepsy Ctr, Los Angeles, CA 90073 USA. RP Cornford, EM (reprint author), Univ Calif Los Angeles, Sch Med, Brain Res Inst, Dept Neurol, Los Angeles, CA 90095 USA. EM cornford@ucla.edu FU NIDDK NIH HHS [DK 19567]; NIGMS NIH HHS [GM 2094]; NINDS NIH HHS [NS 37360] NR 69 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD JUN PY 2001 VL 87 IS 3 BP 510 EP 521 PG 12 WC Parasitology SC Parasitology GA 444GP UT WOS:000169392000006 PM 11426712 ER PT J AU Rapaport, R Nuzzo, J Schatz, D Maclaren, N AF Rapaport, R Nuzzo, J Schatz, D Maclaren, N TI Intervention to delay the onset of diabetes mellitus in very young siblings of children with type 1 diabetes mellitus SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 9th International Beilinson-Schneider Symposium on Children with Parents or Siblings with Diabetes CY SEP 22-25, 2000 CL GALILEE, ISRAEL DE diabetes mellitus; delay; prevention; young; siblings ID PREVENTION; INSULIN; RISK; TIME; AGE C1 CUNY Mt Sinai Sch Med, Mt Sinai Diabet Ctr, Div Pediat Endocrinol & Diabet, New York, NY 10029 USA. St Barnabas Med Ctr, Joslin Diabet Ctr, Div Pediat, Livingston, NJ USA. Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32611 USA. Cornell Univ, Weill Med Coll, Dept Pediat Endocrinol, New York, NY USA. RP Rapaport, R (reprint author), CUNY Mt Sinai Sch Med, Mt Sinai Diabet Ctr, Div Pediat Endocrinol & Diabet, 1200 5th Ave,Box 1616, New York, NY 10029 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD JUN PY 2001 VL 14 SU 1 BP 623 EP 626 PG 4 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 435QU UT WOS:000168893200009 PM 11393554 ER PT J AU Anderson, BJ AF Anderson, BJ TI Children with diabetes mellitus and family functioning: Translating research into practice SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 9th International Beilinson-Schneider Symposium on Children with Parents or Siblings with Diabetes CY SEP 22-25, 2000 CL GALILEE, ISRAEL DE diabetes mellitus management; children; adolescents; family; development; psychosocial research ID METABOLIC CONTROL; GLYCEMIC CONTROL; ADOLESCENTS; MANAGEMENT; INVOLVEMENT; ADHERENCE; CHILDHOOD; DEFICITS; MOTHERS; SUPPORT AB The specific challenges of living with diabetes mellitus (DM) which the child and parent must confront at each developmental stage are identified from infancy through adolescence. This discussion is divided into four developmental stages: 1) DM in infancy (0-2 years of age); 2) DM in toddlers and preschoolers (2-5 years); 3) DM in the school-age child (6-11 years); and 4) DM during early- to mid-adolescence (12-16 years). The central milestones of normal psychosocial development are reviewed and a summary is provided of recent research at each developmental stage with an emphasis on clinical implications for pediatric diabetes care teams. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. RP Anderson, BJ (reprint author), 1920 Albans Rd, Houston, TX 77005 USA. FU NIDDK NIH HHS [DK-46887] NR 50 TC 16 Z9 16 U1 1 U2 4 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD JUN PY 2001 VL 14 SU 1 BP 645 EP 652 PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 435QU UT WOS:000168893200013 PM 11393558 ER PT J AU La Greca, AM Bearman, KJ Delamater, A Patino, AM Blumberg, M Marks, J Johnson, SB Shatz, D Anderson, B AF La Greca, AM Bearman, KJ Delamater, A Patino, AM Blumberg, M Marks, J Johnson, SB Shatz, D Anderson, B TI Early life stress and disease among offspring and siblings of individuals with type 1 diabetes mellitus SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 9th International Beilinson-Schneider Symposium on Children with Parents or Siblings with Diabetes CY SEP 22-25, 2000 CL GALILEE, ISRAEL DE stress; disease; type 1 diabetes mellitus; siblings; offspring ID CHILD-BEHAVIOR PROFILE; AGED 6-11; ADOLESCENTS; ILLNESS; PSYCHOPATHOLOGY; ADJUSTMENT; SUPPORT; FAMILY AB Major life events, recent life stressors, and childhood diseases were examined among children and adolescents who were offspring, siblings, or other relatives of persons with type 1 diabetes mellitus (DM), All youth were recruited as part of a multi-site nationwide trial on the prevention of type 1 DM; parents of 347 children (4 to 18 yr) completed measures that asked about children's life events, recent stressors, and childhood illnesses. Analyses compared age groups (young child, preadolescent, adolescent) and relative type (offspring, sibling, other relative), Findings revealed offspring and siblings did not differ from "other relatives" in terms of life events, recent life stress, and disease/illness variables. However, siblings were reported to have fewer major life events and fewer life stressors in the past 12 months than offspring; siblings also had fewer infectious diseases during the first two years of life compared to offspring. Few age-related differences were found, Overall, results suggest that offspring and siblings of persons with type 1 DM are not at a disadvantage in terms of early life stress or disease in comparison to youth who have other family members with diabetes. However, siblings may have some advantages relative to children who are offspring. The mechanisms underlying these relationships require further elucidation and study. C1 Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. Univ Florida, Gainesville, FL 32611 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP La Greca, AM (reprint author), Univ Miami, Dept Psychol, POB 249229, Coral Gables, FL 33124 USA. NR 23 TC 0 Z9 0 U1 2 U2 5 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD JUN PY 2001 VL 14 SU 1 BP 661 EP 668 PG 8 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 435QU UT WOS:000168893200015 PM 11393560 ER PT J AU Giannobile, WV Lee, CS Tomala, MP Tejeda, KM Zhu, ZM AF Giannobile, WV Lee, CS Tomala, MP Tejeda, KM Zhu, ZM TI Platelet-derived growth factor (PDGF) gene delivery for application in periodontal tissue engineering SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE growth factors, platelet-derived; periodontium/growth; osteogenesis, dental cementum/growth and development; gene therapy ID IN-VITRO; LIGAMENT CELLS; BONE-FORMATION; WOUND REPAIR; FACTOR-BB; THERAPY; REGENERATION; VIVO; EXPRESSION; CEMENTOBLASTS AB Background: A challenge in the reconstruction of periodontal structures is the targeted delivery of growth-promoting molecules to the tooth root surface. Polypeptide growth factors such as platelet-derived growth factor (PDGF) stimulate both cementogenesis and osteogenesis. Recent advances in gene therapy offer the advantage of delivering recombinant proteins to tissues for extended periods of time in vivo. Methods: Recombinant adenoviral vectors encoding for the PDGF-A gene were constructed to allow delivery of PDGF transgenes to cells. The recombinant adenoviruses were assembled using the viral backbone of Ad2/CMV/EGFP and replacing GFP (reporter gene encoding green fluorescent protein driven by the cytomegalovirus promoter [CMV] within adenovirus type 2) with the PDGF-A gene. Root lining cells (cloned cementoblasts) were transduced with Ad2/PDGF-A and evaluated for gene expression, DNA synthesis, and cell proliferation. PDGF-inducible genes, c-myc and osteopontin, were also evaluated following gene delivery of Ad2/PDGF-A. Results: The results revealed high level transduction of cementoblasts by gene transfer for 7 days as evidenced by flow cytometry and Northern blotting. Cementoblast DNA synthesis and subsequent proliferation were stimulated by Ad2/PDGF-A at levels equal to or greater than continuous rhPDGF-AA application. Strong message for the PDGF-A gene and protein as evidenced by Northern blotting and immunocytochemistry was noted. Furthermore, the potent induction of c-myc and osteopontin mRNA was found after PDGF gene delivery to cementoblasts. Conclusions: These findings demonstrate that gene delivery of platelet-derived growth factor stimulates cementoblast activity that is sustained above that of rhPDGF-AA application. The use of gene therapy as a mode of growth factor delivery offers a novel approach to periodontal tissue engineering. C1 Univ Michigan, Dept Periodont Prevent Geriatr, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Biorestorat Oral Hlth, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Giannobile, WV (reprint author), Univ Michigan, Dept Periodont Prevent Geriatr, 1011 N Univ Ave, Ann Arbor, MI 48109 USA. OI Giannobile, William/0000-0002-7102-9746 FU NIDCR NIH HHS [R01 DE013397-01, DE13397, T35 DE007101, R29 DE011960, R01 DE013397, R29 DE011960-03, 5T35 DE07101, T35 DE007101-19, DE11960] NR 47 TC 60 Z9 71 U1 0 U2 1 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD JUN PY 2001 VL 72 IS 6 BP 815 EP 823 DI 10.1902/jop.2001.72.6.815 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 446AT UT WOS:000169491300016 PM 11453245 ER PT J AU Keuthen, NJ Wilhelm, S Deckersbach, T Engelhard, IM Forker, AE Baer, L Jenike, MA AF Keuthen, NJ Wilhelm, S Deckersbach, T Engelhard, IM Forker, AE Baer, L Jenike, MA TI The Skin Picking Scale - Scale construction and psychometric analyses SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE excoriation; self-report scale; skin picking ID MGH HAIRPULLING SCALE; TRICHOTILLOMANIA; CLOMIPRAMINE; RELIABILITY; DESIPRAMINE; DISORDER; SYMPTOM AB Objective: This paper reports on the development of the Skin Picking Scale (SPS), a six-item paper-and-pencil measure for the assessment of skin picking. Methods: 28 severe self-injurious and 77 non-self-injurious skin pickers initially completed an eight-item severity scale modeled after the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Results: Group comparisons and part-whole correlations for individual scale items resulted in a six-item scale with a total score range of 0-24. A Cronbach's alpha coefficient of .80 indicated moderate internal consistency for the scale. Construct validity was demonstrated by significant correlations between SPS total scale scores and self-reported average duration of skin picking episodes. Significant correlations were also reported between SPS total scale scores and both Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) scores, as well as self-reported intensity of emotions during the picking process. Lastly, sensitivity and specificity analyses suggest that a SPS cut-off score of 7 differentiates severe self-injurious and non-self-injurious skin pickers. Conclusion: The SPS is a valid and reliable self-report scale for the assessment of severity in medical and psychiatric patients who endorse skin picking. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp E 9106, OCD Clin & Res Unit, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp E 9106, OCD Clin & Res Unit, Dept Psychiat, 149 13th St, Charlestown, MA 02129 USA. RI Citations, TLC SAB/C-4006-2011 NR 24 TC 46 Z9 46 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD JUN PY 2001 VL 50 IS 6 BP 337 EP 341 DI 10.1016/S0022-3999(01)00215-X PG 5 WC Psychiatry SC Psychiatry GA 447BH UT WOS:000169548300006 PM 11438115 ER PT J AU Mattos-Graner, RO Correa, MSNP Latorre, MDD Peres, RCR Mayer, MPA AF Mattos-Graner, RO Correa, MSNP Latorre, MDD Peres, RCR Mayer, MPA TI Mutans streptococci oral colonization in 12-30-month-old Brazilian children over a one-year follow-up period SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE children; mutans streptococci; dental caries; diet; dental plaque ID DENTAL-CARIES; INITIAL ACQUISITION; YOUNG-CHILDREN; INFANTS; PREVALENCE; LACTOBACILLI; EXPERIENCE; MOTHERS; OLD AB Objectives: The infection levels of mutans streptococci were investigated during a one-year follow-up in children aged 12 to 30 months attending school nurseries where a sucrose-rich diet was provided. Methods: Oral levels of mutans streptococci obtained from 101 children at baseline and after a one-year follow-up were compared by age, number of teeth, feeding habits, and presence of visible plaque at baseline. Baseline predictors and changes in mutans streptococci levels during the study were compared to caries incidence after one year Results: Fluctuations in mutans streptococci levels during the follow-up period were not related to feeding habits or presence of visible plaque. Mutans streptococci levels increased after one year among children aged 12 to 24 months, while a significantly higher proportion of those aged 25-30 months showed a decrease in mutans streptococci levels during the study. Multiple logistic regression analysis suggested that high levels of mutans streptococci (greater than or equal to 100 cfu) at baseline were associated with a higher caries increment, while reduction in mutans streptococci was negatively associated with caries incidence. Conclusions: Our data suggest that despite early mutans streptococci infection and high exposure to sucrose, mutans streptococci may achieve relatively stable levels after 2 years of age. Heavy colonization by mutans streptococci in an early age was related to an extremely high caries incidence during childhood, while decreasing levels of mutans streptococci can be associated to the decrease in caries activity. C1 Sch Dent Sao Paulo, Dept Pediat Dent, Sao Paulo, Brazil. Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, Brazil. Univ Sao Paulo, Sch Publ Hlth, Dept Epidemiol, Sao Paulo, Brazil. Univ Campinas, Dept Pediat Dent, Sch Dent Piracicaba, Piracicaba, Brazil. RP Mattos-Graner, RO (reprint author), Forsyth Inst, Dept Immunol, 140 The Fenway, Boston, MA 02115 USA. RI Mattos-Graner, Renata/C-9410-2012; Mayer, Marcia/D-4645-2012; Latorre, Maria/J-5780-2014 OI Mattos-Graner, Renata/0000-0001-8309-8135; Mayer, Marcia/0000-0002-5910-8433; Latorre, Maria/0000-0002-5189-3457 NR 21 TC 22 Z9 22 U1 0 U2 6 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SUM PY 2001 VL 61 IS 3 BP 161 EP 167 DI 10.1111/j.1752-7325.2001.tb03384.x PG 7 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 472FU UT WOS:000170973500006 PM 11642222 ER PT J AU Finkelstein, DM Schoenfeld, DA AF Finkelstein, DM Schoenfeld, DA TI Comparing treatment strategies using a synthesized clinical trial: an analysis of late versus early use of trimethoprim-sulfamethoxazole for AIDS patients SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE survival; progression; semi-Markov; AIDS ID RISK; ALLOCATION AB This paper applies methodology of Finkelstein and Schoenfeld [Stat. Med. 13 (1994) 1747.] to consider new treatment strategies in a synthetic clinical trial. The methodology is an approach for estimating survival functions as a composite of subdistributions defined by an auxiliary event which is intermediate to the failure. The subdistributions are usually calculated utilizing all subjects in a study, by taking into account the path determined by each individual's auxiliary event. However, the method can be used to get a composite estimate of failure from different subpopulations of patients. We utilize this application of the methodology to test a new treatment strategy, that changes therapy at later stages of disease, by combining subdistributions from different treatment arms of a clinical trial that was conducted to test therapies for prevention of pneumocystis carinii pneumonia. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, MGH Biostat Ctr, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUN 1 PY 2001 VL 96 IS 1 SI SI BP 179 EP 189 DI 10.1016/S0378-3758(00)00334-7 PG 11 WC Statistics & Probability SC Mathematics GA 430RL UT WOS:000168589300012 ER PT J AU Greene, RW Biederman, J Faraone, SV Monuteaux, MC Mick, E DuPre, EP Fine, CS Goring, JC AF Greene, RW Biederman, J Faraone, SV Monuteaux, MC Mick, E DuPre, EP Fine, CS Goring, JC TI Social impairment in girls with ADHD: Patterns, gender comparisons, and correlates SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; social impairment; psychiatric comorbidity ID ATTENTION-DEFICIT HYPERACTIVITY; PSYCHIATRIC-DISORDERS; ADJUSTMENT INVENTORY; CHILDREN; ADOLESCENTS; BOYS; DISABILITY; PROBANDS; FAMILY AB Objective: To investigate social impairment in girls with attention-deficit/hyperactivity disorder (ADHD), compare the social functioning of boys and girls with ADHD, and explore the association between social dysfunction and conditions comorbid with ADHD. Method: Four groups of index children were studied: 267 children (127 girls) with ADHD and 234 non-ADHD comparison children (114 girls). Groups were compared on social functioning. psychopathology, and demographic characteristics. Results: Girls with ADHD manifested significant deficits in interpersonal functioning compared with girls without ADHD and evidenced a similar degree of social impairment compared with boys with ADHD. ADHD and associated comorbid disorders were significant correlates of specific domains of social dysfunction in boys and girls with ADHD. Conclusions: Interpersonal deficits are a major correlate of ADHD, irrespective of gender, and appear to stem from the behaviors associated with ADHD as well as behaviors characteristic of conditions comorbid with ADHD. C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Greene, RW (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, ACC-725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-50657-04] NR 27 TC 74 Z9 78 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 2001 VL 40 IS 6 BP 704 EP 710 DI 10.1097/00004583-200106000-00016 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 433XR UT WOS:000168786400016 PM 11392349 ER PT J AU Schmidt, U Han, RO DiSalvo, TG Guerrero, JL Gold, HK Zapol, WM Bloch, KD Semigran, MJ AF Schmidt, U Han, RO DiSalvo, TG Guerrero, JL Gold, HK Zapol, WM Bloch, KD Semigran, MJ TI Cessation of platelet-mediated cyclic canine coronary occlusion after thrombolysis by combining nitric oxide inhalation with phosphodiesterase-5 inhibition SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID S-NITROSOHEMOGLOBIN; BLEEDING-TIME; AGGREGATION; THERAPY; NITROSOTHIOLS; DIPYRIDAMOLE; ASPIRIN AB OBJECTIVES We sought to evaluate the ability of type 5 phosphodiesterase (PDE5) inhibitors to augment the antithrombotic effects of inhaled nitric oxide (NO) in a canine model of platelet-mediated coronary thrombosis after thrombolysis. BACKGROUND Type 5 phosphodiesterase inhibitors potentiate the ability of NO to inhibit platelet aggregation in vitro by preventing platelet cyclic guanosine monophosphate catabolism. We previously reported that breathing low concentrations of NO gas attenuated, but did not prevent, cyclic flow reductions (CFRs) in a canine model of coronary thrombosis after thrombolysis. METHODS Cyclic flow reductions were induced after creation of a left anterior descending coronary artery stenosis, endothelial injury, thrombus formation and thrombolysis. Dogs were either untreated or treated with inhaled NO (20 ppm by volume), intravenous zaprinast, intravenous dipyridamole or the combination of inhaled NO with either PDE5 inhibitor (n = 4 per group). RESULTS Cyclic flow reductions ceased, and complete coronary patency was achieved in all dogs after they breathed NO combined with zaprinast (by 12.0 +/- 4.7 min [mean +/- SEM]) or dipyridamole (by 9.8 +/- 4.7 min). The frequency of CFRs was unaffected by NO, dipyridamole or zaprinast alone. Systemic arterial blood pressure and bleeding time were unchanged with any treatment. Ex vivo thrombin-induced platelet aggregation in dogs breathing NO and receiving dipyidamole was reduced by 75 +/- 7% (p < 0.05). CONCLUSIONS The PDE5 inhibitors potentiated the antithrombotic properties of inhaled NO in a canine model of platelet-mediated coronary artery thrombosis after thrombolysis, without prolonging the bleeding time or causing systemic hypotension. (J Am Coll Cardiol 2001;37:1981-8) (C) 2001 by the American College of Cardiology. C1 Massachusetts Gen Hosp, Div Cardiol, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Anesthesia & Crit Care, Bigelow 626, Boston, MA 02114 USA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 FU NHLBI NIH HHS [HL-55377, HL-04021, HL-42397] NR 30 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 1 PY 2001 VL 37 IS 7 BP 1981 EP 1988 DI 10.1016/S0735-1097(01)01270-0 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 439EE UT WOS:000169097200035 PM 11401142 ER PT J AU Simon, JA Hudes, ES Tice, JA AF Simon, JA Hudes, ES Tice, JA TI Relation of serum ascorbic acid to mortality among US adults SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE antioxidants; ascorbic acid; cancer; cardiovascular disease; mortality; vitamin C ID ENDOTHELIUM-DEPENDENT VASODILATION; LOW-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; VITAMIN-E CONSUMPTION; CARDIOVASCULAR-DISEASE; LIPID-PEROXIDATION; DIABETES-MELLITUS; AORTIC RINGS; C STATUS; PLASMA AB Purpose: To examine the relation between serum ascorbic acid (SAA), a marker of dietary intake (including supplements), and cause-specific mortality. Subjects and Methods: We analyzed data from a probability sample of 8,453 Americans age greater than or equal to 30 years at baseline enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), who were followed for mortality endpoints. We calculated relative hazard ratios as measures of disease association comparing the mortality rates in three biologically relevant SAA categories. Results: participants with normal to high SAA levels had a marginally significant 21% to 25% decreased risk of fatal cardiovascular disease (CVD) (p for trend = 0.09) and a 25% to 29% decreased risk of all-cause mortality (p for trend < 0.001) compared to participants with low levels. Because we determined that gender modified the association between SAA levels and cancer death, we analyzed these associations stratified by gender. Among men, normal to high SAA levels were associated with an approximately 30% decreased risk of cancer deaths, whereas such SAA levels were associated with an approximately two-fold increased risk of cancer deaths among women. This association among women persisted even after adjustment for baseline prevalent cancer and exclusion for early cancer death or exclusion for prevalent cancer. Conclusions: Low SAA levels were marginally associated with an increased risk of fatal CVD and significantly associated with an increased risk for all-cause mortality. Low SAA levels were also a risk factor for cancer death in men, bur unexpectedly were associated with a decreased risk of cancer death in women. If the association between low SAA levels and all-cause mortality is causal, increasing the consumption of ascorbic acid, and thereby SAA levels, could decrease the risk of death among Americans with low ascorbic acid intakes. C1 San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, Med Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Simon, JA (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, Med Serv, 4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [HL53479] NR 58 TC 50 Z9 51 U1 1 U2 1 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD JUN PY 2001 VL 20 IS 3 BP 255 EP 263 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 448KH UT WOS:000169625700008 PM 11444422 ER PT J AU Mathisen, DJ AF Mathisen, DJ TI What's new in general thoracic surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID CELL LUNG-CANCER; VOLUME-REDUCTION SURGERY; POSTOPERATIVE ADJUVANT THERAPY; POSITRON-EMISSION-TOMOGRAPHY; ISCHEMIA-REPERFUSION INJURY; LONG-TERM SURVIVAL; STAGE-II; ESOPHAGEAL CANCER; SEVERE EMPHYSEMA; TRANSPLANTATION C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 1109,32 Fruit St, Boston, MA 02114 USA. NR 62 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD JUN PY 2001 VL 192 IS 6 BP 737 EP 749 DI 10.1016/S1072-7515(01)00933-4 PG 13 WC Surgery SC Surgery GA 438FT UT WOS:000169043500011 PM 11400968 ER PT J AU Skates, SJ Pauler, DK Jacobs, IJ AF Skates, SJ Pauler, DK Jacobs, IJ TI Screening based on the risk of cancer calculation from Bayesian hierarchical changepoint and mixture models of longitudinal markers SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE longitudinal CA125; Markov chain Monte Carlo; mixtures; ovarian cancer; screening ID OVARIAN-CANCER; SERUM CA-125; IDENTIFICATION; TIME AB The standard approach to early detection of disease with a quantitative marker is to set a population-based fixed reference level for making further individual screening or referral decisions. For many types of disease, including prostate and ovarian cancer, additional information is contained in the subject-specific temporal behavior of the marker, which exhibits a characteristic alteration early in the course of the disease. In this article we derive a Bayesian approach to screening based on calculation of the posterior probability of disease given longitudinal marker levels. The method is motivated by a randomized ovarian cancer screening trial in the United Kingdom comprising 22,000 women screened over 4 years with an additional 5 years of follow-up on average. Levels of the antigen CA125 were recorded annually in the screened arm. CA125 profiles of cases and controls from the U.K. trial are modeled using hierarchical changepoint and mixture models, posterior distributions are calculated using Markov chain Monte Carlo methods, and the model is used to calculate the Bayesian posterior risk of having ovarian cancer given a new subject's single or multiple longitudinal CA125 levels. A screening strategy based on the risk calculation is then evaluated using data from an independent screening trial of 5,550 women performed in Sweden. A longitudinal CA125 screening strategy based on calculation of the risk of ovarian cancer is proposed. Simulations of a prospective trial using a strategy based on the risk calculated from longitudinal CA125 values indicate potentially large increases in sensitivity for a given specificity compared to the standard approach based on a fixed CA125 reference level for all subjects. C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ London Queen Mary & Westfield Coll, St Bartholomews & Royal London Sch Med, London EC1A 7BE, England. RP Skates, SJ (reprint author), Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RI Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 30 TC 71 Z9 72 U1 0 U2 14 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 2001 VL 96 IS 454 BP 429 EP 439 DI 10.1198/016214501753168145 PG 11 WC Statistics & Probability SC Mathematics GA 437HN UT WOS:000168986400007 ER PT J AU Wong, WR Kossodo, S Kochevar, IE AF Wong, WR Kossodo, S Kochevar, IE TI Influence of cytokines on matrix metalloproteinases produced by fibroblasts cultured in monolayer and collagen gels SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Article DE photoaging; matrix metalloproteinase; collagen gel; cytokines ID NECROSIS-FACTOR-ALPHA; HUMAN DERMAL FIBROBLASTS; ELASTIN GENE-EXPRESSION; HUMAN SKIN FIBROBLASTS; HUMAN KERATINOCYTES; ULTRAVIOLET-LIGHT; IN-VITRO; INTERLEUKIN-10; STIMULATION; IRRADIATION AB Background: Extracellular matrix metalloproteinases (MMPs) are crucial factors involved in connective tissue remodeling that accompanies ultraviolet radiation-induced actinic damage. This study investigated whether the cytokines tumor necrosis factor (TNF)-alpha. interleukin (IL)-1 beta, and IL-10 modulate the expression of MMPs in cultured human newborn skin fibroblasts. Methods: Different c concentrations of TNF-alpha, IL-1 beta, and IL-10 were added to human dermal fibroblasts grown in monolayers or embedded in three-dimensional (3D) collagen gels, a model closer to skin. Supernatant from the fibroblast cell culture was collected 24 hours later. The concentrations of MMP-1 and MMP-3 were assaysed by enzyme-linked immunosorbent assay (ELISA) while the concentrations of MMP-2 and MMP-9 were analysed by zymography. Results: Basal production of MMPs was significantly greater in fibroblasts grown in 3D gels than in cells grown as monolayers. TNF-alpha and IL-1 beta induced increases in the concentrations of MMP-1, MMP-3. and MMP-9, but not in MMP-2 or tissue inhibitor of matrix metalloproteinase (TIMP)-1 or -2. The inducibility of MMP secretion is more significant in 3D gels. IL-10 did not significantly modulate MMPs. Conclusion: This study demonstrated that basal concentrations of MMPs are higher in fibroblasts cultured in 3D gels and their response to cytokines is different to that of cells grown as monolayers. Cytokines can increase the collagenolytic and gelatinolytic activity involved in extracellular matrix remodeling and hence contributing to photoaging. C1 Chang Gung Mem Hosp, Dept Dermatol, Taipei 10591, Taiwan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02115 USA. RP Wong, WR (reprint author), Chang Gung Mem Hosp, Dept Dermatol, 199 Tung Hwa N Rd, Taipei 10591, Taiwan. NR 43 TC 28 Z9 33 U1 0 U2 0 PU EXCERPTA MEDICA ASIA LTD PI CHAI WAN PA 19/F, EIGHT COMMERCIAL TOWER, 8 SUN YIP ST, CHAI WAN, HONG KONG SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD JUN PY 2001 VL 100 IS 6 BP 377 EP 382 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 451JQ UT WOS:000169799300003 PM 11480246 ER PT J AU Brewster, DC AF Brewster, DC TI Presidential address: What would you do if it were your father? Reflections on endovascular abdominal aortic aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Editorial Material ID POPULATION-BASED ANALYSIS; STENT-GRAFT TREATMENT; LIFE-TABLE ANALYSIS; VASCULAR-SURGERY; ENDOLUMINAL REPAIR; PERIPROSTHETIC LEAK; INITIAL EXPERIENCE; SURGICAL REPAIR; CLINICAL-TRIAL; UNITED-STATES C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Cambridge, MA USA. RP Brewster, DC (reprint author), 1 Hawthorne Pl,Suite 111, Boston, MA 02114 USA. NR 105 TC 19 Z9 21 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2001 VL 33 IS 6 BP 1139 EP 1147 DI 10.1067/mva.2001.115374 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 444TR UT WOS:000169416600001 PM 11389410 ER PT J AU Lauterbach, SR Cambria, RP Brewster, DC Gertler, JP LaMuraglia, GM Isselbacher, EM Hilgenberg, AD Moncure, AC AF Lauterbach, SR Cambria, RP Brewster, DC Gertler, JP LaMuraglia, GM Isselbacher, EM Hilgenberg, AD Moncure, AC TI Contemporary management of aortic branch compromise resulting from acute aortic dissection SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID PERIPHERAL VASCULAR COMPLICATIONS; STENT-GRAFT PLACEMENT; ISCHEMIC COMPLICATIONS; BALLOON FENESTRATION; FOLLOW-UP; ANEURYSMS; MALPERFUSION AB Purpose: In an earlier report, we documented the incidence and impact of aortic branch compromise complicating acute aortic dissection (AD) over a 21-year interval (1965-1986). In the current study, management of peripheral vascular complications (PVCs) of AD over the past decade was reviewed. Methods: Medical records of patients treated for AD over the interval January 1, 1990, to December 31, 1999, were reviewed. Patients with branch compromise confirmed with radiography or operation and patients with spinal cord ischemia that was based on results of a physical examination defined the study group. Comparisons between subgroups with and without PVC over a 30-year interval were analyzed with the chi (2) test. Results: A total of 187 patients (101 proximal and 86 distal) were treated for AD over the study interval. A total of 53 (28%) of these patients had clinical evidence of organ or limb malperfusion (7 cerebral, 3 upper extremity, 5 spinal cord, II mesenteric, 12 renal, and 24 lower extremity [sites inclusive]), and one of three (17 patients) of these underwent specific peripheral vascular intervention. The remaining 65% (36) of the PVC group had complete or partial malperfusion resolution after central aortic therapy (medical or surgical) alone. Open techniques for treating PVC included aortic fenestration (9), femorofemoral grafting (2), and aortofemoral grafting (1). All had favorable outcomes with no mortality. Endovascular procedures in five patients included abdominal aortic fenestration (3) or stenting of the renal (2), mesenteric (2), and iliac (1) arteries with clinical success in three patients and two deaths. The in-hospital mortality rate for the entire group of 187 patients was 18% (15% for proximal aortic operation, 8% in medically treated patients). The presence of aortic branch compromise was not a statistically significant predictor of the patient mortality rate (23% with and 16% without; P =.26). Overall mortality rate in the current study (18% vs 37%; P =.000006) and the mortality rate with PVC (23% vs 51%; P =.001), in particular with mesenteric ischemia (36% vs 87%; P =.026), decreased significantly when compared with prior experience. Conclusions: The overall mortality rate from AD during the past decade has decreased significantly. Similar trends were noted in patients with PVCs, a previously identified high-risk subgroup. Increased awareness and prompt, specific management of PVCs, in particular when visceral ischemia is present, have contributed to improved outcomes in patients with AD. C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, 15 Parkman St,WAC 458, Boston, MA 02114 USA. NR 31 TC 86 Z9 99 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2001 VL 33 IS 6 BP 1185 EP 1192 DI 10.1067/mva.2001.115377 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 444TR UT WOS:000169416600011 PM 11389416 ER PT J AU Casey, PJ Dattilo, JB Dai, GH Albert, JA Tsukurov, OI Orkin, RW Gertler, JP Abbott, WM AF Casey, PJ Dattilo, JB Dai, GH Albert, JA Tsukurov, OI Orkin, RW Gertler, JP Abbott, WM TI The effect of combined arterial hemodynamics on saphenous venous endothelial nitric oxide production SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY OCT 04-07, 2000 CL BOSTON, MASSACHUSETTS SP New England Soc Vasc Surg ID AUTOGENOUS VEIN GRAFTS; FLUID SHEAR-STRESS; INTIMAL HYPERPLASIA; CYCLIC STRAIN; VASCULAR WALL; L-ARGININE; IN-VITRO; CELLS; PHYSIOLOGY; FLOW AB Introduction: Evidence exists that an ideal bypass conduit should have a functional endothelial cell surface combined with mechanical properties similar to those of native arteries. We hypothesized that the effect of combined arterial levels of pulsatile shear stress, flow, and cyclic strain would enhance saphenous venous endothelial cell nitric oxide (NO) production, and that variations in these "ideal" conditions could impair this function. We studied NO production as a measure of endothelial function in response to different hemodynamic conditions. Methods: Human adult saphenous venous endothelial cells were cultured in 10-cm silicone tubes, similar in diameter (5 mm) and compliance (6%) to a medium-caliber peripheral artery (eg, popliteal). Tube cultures were exposed to arterial conditions: a combined pressure (120/80 mm/Hg; mean, 100 mm/Hg), flow (mean, 115 mL/min) and cyclic strain (2%), with a resultant pulsatile shear stress of 4.8 to 9.4 dyne/cm(2) (mean, 7.1). Identical tube cultures were used to study variations in these conditions. Modifications of the system included a noncompliant system, a model with non-pulsatile flow, and a final group exposed to pulsatile pressure with no flow NO levels were measured with, fluorometric nitrite assay of conditioned media collected at 0, 0.25, 0.5, 1, 2, and 4 hours. Experimental groups were compared with cells exposed to nonpulsatile, nonpressurized low flow (shear stress 0.1 dyne/cm(2)) and static cultures. Results: Ah experimental groups had greater rates of NO production than cells under static conditions (P < .05). Cells exposed to ideal conditions produced the greatest levels of NO. Independent decreases in compliance, flow, and pulsatility resulted in significantly lower rates of NO production than those in the group with these conditions intact (vs noncompliant P < .05, vs nonflow P < .05, and vs nonpulsatile P < .05). Conclusions: Our results show that in the absence of physiologically normal pulsatility, cyclic strain, and Volume flow endothelial NO production does not reach the levels seen under ideal conditions. Pulsatile flow and compliance (producing flow with cyclic stretch) play a key role in NO production by vascular endothelium in a three-dimensional hemodynamically active model. This correlates biologically with clinical experience linking graft inflow and runoff and the mechanical properties of the conduit to long-term patency. C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. RP Abbott, WM (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, 15 Parkman St,WAC 458, Boston, MA 02114 USA. OI Dai, Guohao/0000-0001-7346-2685 FU PHS HHS [52183] NR 29 TC 28 Z9 29 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 2001 VL 33 IS 6 BP 1199 EP 1204 DI 10.1067/mva.2001.115571 PG 6 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 444TR UT WOS:000169416600015 PM 11389418 ER PT J AU Chiba, S Okada, K Lee, K Segre, GV Neer, RM AF Chiba, S Okada, K Lee, K Segre, GV Neer, RM TI Molecular analysis of defect healing in rat diaphyseal bone SO JOURNAL OF VETERINARY MEDICAL SCIENCE LA English DT Article DE bone defect healing; bone formation; bone resorption; in situ hybridization; osteoblast ID SYSTEMIC ACCELERATORY PHENOMENON; PARATHYROID-HORMONE; IN-VIVO; EXPRESSION; CELLS AB Spatial expression of messenger ribonucleic acid (mRNA) for osteoblastic marker in drill hole defect healing of adult male rats was analyzed by in situ hybridization. The defect was filled with hematoma 3 days after surgery, expressing Type I collagen mRNA. Hematoma was replaced with fibrous tissue on day 7, and then with new trabecular bone on day 10, originated from the intra-medullary space. respectively. mRNA for Type I collagen, parathyroid hormone 1 receptor (PTH1R), and alkaline phosphatase (ALP) were expressed in the same cell population of fibrous tissue adjacent to newly-formed trabecular bone, and in osteoblasts lining the newly-formed trabecular bone. Hematopoietic marrow with osteoclasts subsequently invaded the region. also from the intra-medullary space, replacing all the new trabecular bone by day 21, except for a thin sub-periosteal layer. mRNA for Type I collagen, PTH1R and ALP was expressed on the periosteal surface of thin layer. Although cartilage formation was not histologically visible, mRNA for Type II collagen was weakly detected in the majority of osteoblasts lining the newly-formed trabecular bone. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Iwate Univ, Fac Agr, Dept Vet Pathol, Morioka, Iwate 0208550, Japan. RP Chiba, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Fruit St, Boston, MA 02114 USA. NR 14 TC 11 Z9 11 U1 0 U2 0 PU JAPAN SOC VET SCI PI TOKYO PA UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO, 103, JAPAN SN 0916-7250 J9 J VET MED SCI JI J. Vet. Med. Sci. PD JUN PY 2001 VL 63 IS 6 BP 603 EP 608 DI 10.1292/jvms.63.603 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 452FN UT WOS:000169847000003 PM 11459005 ER PT J AU Bacheler, L Jeffrey, S Hanna, G D'Aquila, R Wallace, L Logue, K Cordova, B Hertogs, K Larder, B Buckery, R Baker, D Gallagher, K Scarnati, H Tritch, R Rizzo, C AF Bacheler, L Jeffrey, S Hanna, G D'Aquila, R Wallace, L Logue, K Cordova, B Hertogs, K Larder, B Buckery, R Baker, D Gallagher, K Scarnati, H Tritch, R Rizzo, C TI Genotypic correlates of phenotypic resistance to efavirenz in virus isolates from patients failing nonnucleoside reverse transcriptase inhibitor therapy SO JOURNAL OF VIROLOGY LA English DT Article ID ANTIRETROVIRAL DRUGS; ANTIVIRAL ACTIVITY; TYPE-1; HIV-1; MUTATIONS; PROTEASE; ZIDOVUDINE; INFECTION; SUSCEPTIBILITIES; COMBINATION AB Efavirenz (also known as DMP 266 or SUSTIVA) is a potent nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity and of HIV-1 replication in vitro and in vivo. Most patients on efavirenz-containing regimens have sustained antiviral responses; however, rebounds in plasma viral load have been observed in some patients in association with the emergence of mutant strains of HIV-1, Virus isolates from the peripheral blood mononuclear cells (PBMCs) of patients with such treatment failures, as well as recombinant viruses incorporating viral sequences derived from patient plasma, show reduced in vitro susceptibility to efavirenz in association with mutations in the RT gene encoding K103N, Y188L, or G190S/E substitutions. Patterns of RT gene mutations and in vitro susceptibility were similar in plasma virus and in viruses isolated from PBMCs. Variant strains of HIV-1 constructed by site-directed mutagenesis confirmed the role of K103N, G190S, and Y188L substitutions in reduced susceptibility to efavirenz. Further, certain secondary mutations (V106I, V108I, Y181C, Y188H, P225H, and F227L) conferred little resistance to efavirenz as single mutations but enhanced the level of resistance of viruses carrying these mutations in combination with K103N or Y188L. Viruses with K103N or Y188L mutations, regardless of the initial selecting nonnucleoside RT inhibitor (NNRT1), exhibited cross-resistance to all of the presently available NNRT1s (efavirenz, nevirapine, and delavirdine). Some virus isolates from nevirapine or delavirdine treatment failures that lacked K103N or Y188L mutations remained susceptible to efavirenz in vitro, although the clinical significance of this finding is presently unclear. C1 Dupont Merck Pharmaceut Co, Expt Stn E33636B, Wilmington, DE 19880 USA. Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Virco UK, Cambridge, England. Virco NV, Mechelen, Belgium. RP Bacheler, L (reprint author), Dupont Merck Pharmaceut Co, Expt Stn E33636B, Wilmington, DE 19880 USA. NR 33 TC 170 Z9 180 U1 1 U2 7 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 JUN PY 2001 VL 75 IS 11 BP 4999 EP 5008 DI 10.1128/JVI.75.11.4999-5008.2001 PG 10 WC Virology SC Virology GA 430UJ UT WOS:000168593600006 PM 11333879 ER PT J AU Bultmann, A Muranyi, W Seed, B Haas, J AF Bultmann, A Muranyi, W Seed, B Haas, J TI Identification of two sequences in the cytoplasmic tail of the human immunodeficiency virus type 1 envelope glycoprotein that inhibit cell surface expression SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL MESSENGER-RNA; TRANS-GOLGI NETWORK; INTRACELLULAR-TRANSPORT; TRANSMEMBRANE PROTEIN; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; ENDOPROTEOLYTIC CLEAVAGE; INTRACYTOPLASMIC DOMAIN; ENV GLYCOPROTEIN; FUSION ACTIVITY AB During synthesis and export of protein, the majority of the human immunodeficiency virus type 1 (HIV-1) Env glycoprotein gp160 is retained in the endoplasmic reticulum (ER) and subsequently ubiquitinated and degraded by proteasomes. Only a small fraction of gp160 appears to be correctly folded and processed and is transported to the cell surface, which makes it difficult to identify negative sequence elements regulating steady-state surface expression of Env at the post-ER level. Moreover, poorly localized mRNA retention sequences inhibiting the nucleocytoplasmic transport of viral transcripts interfere with the identification of these sequence elements. Using two heterologous systems with CD4 or immunoglobulin extracellular/transmembrane domains in combination with the gp160 cytoplasmic domain, we were able to identify two membrane-distal, neighboring motifs, is1 (amino acids 750 to 763) and is2 (amino acids 764 to 785), which inhibited surface expression and induced Golgi localization of the chimeric proteins. To prove that these two elements act similarly in the homologous context of the Env glycoprotein, we generated a synthetic gp160 gene with synonymous codons, the transcripts of which are not retained within the nucleus. In accordance with the results in heterologous systems, an internal deletion of both elements considerably increased surface expression of gp160. C1 Univ Munich, Genzentrum, Max von Pettenkofer Inst, D-81377 Munich, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. RP Haas, J (reprint author), Univ Munich, Genzentrum, Max von Pettenkofer Inst, Feodor Lynen Str 25, D-81377 Munich, Germany. NR 74 TC 43 Z9 43 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 JUN PY 2001 VL 75 IS 11 BP 5263 EP 5276 DI 10.1128/JVI.75.11.5263-5276.2001 PG 14 WC Virology SC Virology GA 430UJ UT WOS:000168593600035 PM 11333908 ER PT J AU Gruener, NH Lechner, F Jung, MC Diepolder, H Gerlach, T Lauer, G Walker, B Sullivan, J Phillips, R Pape, GR Klenerman, P AF Gruener, NH Lechner, F Jung, MC Diepolder, H Gerlach, T Lauer, G Walker, B Sullivan, J Phillips, R Pape, GR Klenerman, P TI Sustained dysfunction of antiviral CD8(+) T lymphocytes after infection with hepatitis C virus SO JOURNAL OF VIROLOGY LA English DT Article ID CHORIOMENINGITIS VIRUS; QUANTITATIVE-ANALYSIS; EFFECTOR FUNCTION; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; VIRAL CLEARANCE; IN-VIVO; CELLS; PERSISTENCE; SPECIFICITY AB Hepatitis C virus (HCV) sets up persistent infection in the majority of those exposed. It is likely that, as with other persistent viral infections, the efficacy of T-lymphocyte responses influences long-term outcome. However, little is known about the functional capacity of HCV-specific T-lymphocyte responses induced after acute infection. We investigated this by using major histocompatibility complex class I-peptide tetrameric complexes (tetramers), which allow direct detection of specific CD8(+) T lymphocytes ex vivo, independently of function. Here we show that, early after infection, virus-specific CD8(+) T lymphocytes detected with a panel of four such tetramers are abnormal in terms of their synthesis of antiviral cytokines and lytic activity. Furthermore, this phenotype is commonly maintained long term, since large sustained populations of HCV-specific CD8+ T Lymphocytes were identified, which consistently had very poor antiviral cytokine responses as measured in vitro. Overall, HCV-specific CD8(+) T lymphocytes show reduced synthesis of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) after stimulation with either mitogens or peptides, compared to responses to Epstein-Barr virus and/or cytomegalovirus. This behavior of antiviral CD8(+) T lymphocytes induced after HCV infection may contribute to viral persistence through failure to effectively suppress viral replication. C1 John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. Klinikum Grosshadern, Dept Med 2, D-81366 Munich, Germany. Inst Immunol, D-80336 Munich, Germany. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Australian Red Cross Blood Serv, Sydney, NSW 2000, Australia. RP Klenerman, P (reprint author), John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. NR 33 TC 354 Z9 366 U1 1 U2 7 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 JUN PY 2001 VL 75 IS 12 BP 5550 EP 5558 DI 10.1128/JVI.75.12.5550-5558.2001 PG 9 WC Virology SC Virology GA 435JF UT WOS:000168877800013 PM 11356962 ER PT J AU Etemad-Moghadam, B Rhone, D Steenbeke, T Sun, Y Manola, J Gelman, R Fanton, JW Racz, P Tenner-Racz, K Axthelm, MK Letvin, NL Sodroski, J AF Etemad-Moghadam, B Rhone, D Steenbeke, T Sun, Y Manola, J Gelman, R Fanton, JW Racz, P Tenner-Racz, K Axthelm, MK Letvin, NL Sodroski, J TI Membrane-fusing capacity of the human immunodeficiency virus envelope proteins determines the efficiency of CD4(+) T-cell depletion in macaques infected by a simian-human immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID HTLV-III/LAV ENVELOPE; AIDS-LIKE DISEASE; RHESUS-MONKEYS; LYMPH-NODES; HIV-1 INFECTION; ANTIRETROVIRAL THERAPY; PERSISTENT INFECTION; SYNCYTIUM FORMATION; ATOMIC-STRUCTURE; VIRAL BURDEN AB The mechanism of the progressive loss of CD4(+) T lymphocytes, which underlies the development of AIDS in human immunodeficiency virus (HTV-1)-infected individuals, is unknown. Animal models, such as the infection of Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae, can assist studies of HIV-1 pathogenesis, Serial in vivo passage of the nonpathogenic SHIV-89.6 generated a virus, SHIV-89.6P, that causes rapid depletion of CD4(+) T lymphocytes and AIDS-like illness in monkeys. SHIV-KB9, a molecularly cloned virus derived from SHIV-89.6P, also caused CD4(+) T-cell decline and AIDS in inoculated monkeys. It has been demonstrated that changes in the envelope glycoproteins of SHIV-89.6 and SHIV-KB9 determine the degree of CD4(+) T-cell loss that accompanies a given level of virus replication in the host animals (G, B, Karlsson et. al., J. Exp. Med. 188:1159-1171, 1998). The envelope glycoproteins of the pathogenic SHIV mediated membrane fusion more efficiently than those of the parental, nonpathogenic virus. Here we show that the minimal envelope glycoprotein region that specifies this increase in membrane-fusing capacity is sufficient to convert SHIV-89.6 into a virus that causes profound CD4+ T-lymphocyte depletion in monkeys. We also studied two single amino acid changes that decrease the membrane-fusing ability of the SHIV-KB9 envelope glycoproteins by different mechanisms. Each of these changes attenuated the CD4(+) T-cell destruction that accompanied a given level of virus replication in SHIV-infected monkeys. Thus, the ability of the HIV-1 envelope glycoproteins to fuse membranes, which has been implicated in the induction of viral cytopathic effects in vitro, contributes to the capacity of the pathogenic SHIV to deplete CD4(+) T lymphocytes in vivo. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol,Div Viral Pathogenesis, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Bernhard Nocht Inst Trop Med, Dept Pathol, D-20359 Hamburg, Germany. Bernhard Nocht Inst Trop Med, Korber Lab, D-20359 Hamburg, Germany. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI28691, AI33832, P30 AI028691, R01 AI033832] NR 78 TC 57 Z9 58 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 JUN PY 2001 VL 75 IS 12 BP 5646 EP 5655 DI 10.1128/JVI.75.12.5646-5655.2001 PG 10 WC Virology SC Virology GA 435JF UT WOS:000168877800023 PM 11356972 ER PT J AU Rubenstein, LZ Harker, JO Salva, A Guigoz, Y Vellas, B AF Rubenstein, LZ Harker, JO Salva, A Guigoz, Y Vellas, B TI Screening for undernutrition in geriatric practice: Developing the Short-Form Mini-Nutritional Assessment (MNA-SF) SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID INDEX; PROGRESS; CARE; RISK AB Background. The Mini-Nutritional Assessment (MNA) is a validated assessment instrument for nutritional problems, but its length limits its usefulness for screening. We sought to develop a screening version of this instrument, the MNA-SF, that retains good diagnostic accuracy. Methods, We reanalyzed data from France that were used to develop the original MNA and combined these with data collected in Spain and New Mexico. Of the 881 subjects with complete MNA data, 151 were from France, 400 were from Spain. and 330 were from New Mexico. Independent ratings of clinical nutritional status were available for 142 of the French subjects. Overall. 73.8% were community dwelling, and mean age was 76.4 years. Items were chosen for the MNA-SF on the basis of item correlation with the total MNA score and with clinical nutritional status, internal consistency, reliability, completeness, and ease of administration. Results. After testing multiple versions, we identified an optimal six-item MNA-SF total score ranging from 0 to 14. The cut-point score for MNA-SF was calculated using clinical nutritional status as the gold standard (n = 142) and using the total MNA score (n = 881). The MNA-SF was strongly correlated with the total MNA score (r = .945). Using an MNA-SF score of,ll as normal, sensitivity was 97.9%, specificity was 100%, and diagnostic accuracy was 98.7% for predicting undernutrition. Conclusions. The MNA-SF can identify persons with undernutrition and can be used in a two-step screening process in which persons, identified as "at risk" on the MNA-SF, would receive additional assessment to confirm the diagnosis and plan interventions. C1 VA Greater Los Angeles Hlthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Serv Catala Salut, Programe Vida Als Anys, Barcelona, Spain. Nestle Res Ctr, CH-1000 Lausanne, Switzerland. Hop Toulouse, Serv Med Interne & Gerontol Clin, Toulouse, France. RP Rubenstein, LZ (reprint author), VA Greater Los Angeles Hlthcare Syst, Ctr Geriatr Res Educ & Clin, 1611 Plummer St, Sepulveda, CA 91343 USA. NR 17 TC 333 Z9 354 U1 8 U2 24 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 JUN PY 2001 VL 56 IS 6 BP M366 EP M372 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 439NV UT WOS:000169124200016 PM 11382797 ER PT J AU Gibson, KD Caps, MT Kohler, TR Hatsukami, TS Gillen, DL Aldassy, M Sherrard, DJ Stehman-Breen, CO AF Gibson, KD Caps, MT Kohler, TR Hatsukami, TS Gillen, DL Aldassy, M Sherrard, DJ Stehman-Breen, CO TI Assessment of a policy to reduce placement of prosthetic hemodialysis access SO KIDNEY INTERNATIONAL LA English DT Article DE vascular access; access patency; dialysis access; autogenous condiuts; graft patency; fistulas ID TRANSPOSED BASILIC VEIN; BRACHIAL ARTERIOVENOUS-FISTULA; VASCULAR ACCESS; UNITED-STATES; DIALYSIS; POLYTETRAFLUOROETHYLENE; COMPLICATIONS; ANGIOACCESS; EXPERIENCE; MATURATION AB Background. The aim of this study was to evaluate the determinants of access patency and revision, including the effects of reducing the placement of prosthetic hemodialysis access. Methods. A retrospective cohort study of all hemodialysis accesses placed at the Veteran's Administration Puget Sound Health Care System between 1992 and 1999 was conducted. A policy was instituted in 1996 that maximized the use of autogenous hemodialysis access. The impacts of the policy change, demographics, and comorbid factors on access type and patency, were examined. Primary and secondary patency rates were examined using the Kaplan-Meier method, and factors associated with failure and revision were examined using Cox proportional hazard models and Poisson regression. Results. During the study, 104 accesses (61 prosthetic grafts and 43 autogenous fistulas) were placed prior to 1996, and 118 (31 prosthetic grafts and 87 autogenous fistulas) were placed after 1996. There was a significant increase in autogenous fistulas placed after 1996 (87 out of 118) compared with before 1996 (43 out of 104, P < 0.001). At one year, autogenous fistulas demonstrated superior primary patency (56 vs. 36%, P = 0.001) and secondary patency (72 vs. 58%, P = 0.003) compared with prosthetic grafts. After adjustment for age, race, side of access placement, and history of prior access placement, patients with a prosthetic graft were estimated to experience a 78% increase in the risk of primary access failure when compared with similar patients having an autogenous access [adjusted relative risk (aRR) = 1.78, 95% CI 1.21-2.62, P = 0.003)]. Similarly, the adjusted relative risk of secondary access failure for comparing prosthetic grafts with autogenous fistulas was estimated to be 2.21 (95% CI 1.38-3.54, P = 0.001). The adjusted risk of access revision was 2.89-fold higher for prosthetic grafts than for autogenous fistulas (95% CI 1.88-4.44, P < 0.001). Conclusions. Autogenous conduits demonstrated superior performance when compared with prosthetic grafts in terms of primary and secondary patency and number of revisions. A policy emphasizing the preferential placement of autogenous fistulas over prosthetic grafts may result in improved patency and a reduction in the number of procedures required to maintain dialysis access patency. C1 Univ Washington, Sch Med, Dept Vasc Surg, Seattle, WA USA. Univ Washington, Sch Med, Dept Biostat, Seattle, WA USA. Univ Washington, Sch Med, Dept Med, Div Nephrol, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Kaiser Permanente, Dept Vasc Surg, Honolulu, HI USA. RP Gibson, KD (reprint author), Univ Washington, Dept Surg, Box 356410,1959 NE Pacific St, Seattle, WA 98195 USA. FU NIDDK NIH HHS [DK07721-6] NR 36 TC 73 Z9 75 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2001 VL 59 IS 6 BP 2335 EP 2345 DI 10.1046/j.1523-1755.2001.0590062335.x PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 431ER UT WOS:000168619300036 PM 11380838 ER PT J AU Alessandri, G Girelli, M Taccagni, G Colombo, A Nicosia, R Caruso, A Baronio, M Pagano, S Cova, L Parati, E AF Alessandri, G Girelli, M Taccagni, G Colombo, A Nicosia, R Caruso, A Baronio, M Pagano, S Cova, L Parati, E TI Human vasculogenesis ex vivo: Embryonal aorta as a tool for isolation of endothelial cell progenitors SO LABORATORY INVESTIGATION LA English DT Article ID STEM-CELLS; IN-VITRO; ANGIOGENESIS INVITRO; DIFFERENTIATION; CULTURE; ASSAY AB Vasculogenesis, the de novo formation of new blood vessels from undifferentiated precursor cells or angioblasts, has been studied with experimental in vivo and ex vivo animal models, but its mechanism is poorly understood, particularly in humans. We used the aortic ring assay to investigate the angioforming capacity of aortic explants from 11- to 12-week-old human embryos. After being embedded in collagen gels, the aorta rings produced branching capillary-like structures formed by mesenchymal spindle cells that lined a capillary-like lumen and expressed markers of endothelial differentiation (CD31, CD34, von Willebrand factor [VWF], and fms-like tyrosine kinase-1 [Flk-1]/vascular endothelial growth factor receptor 2 [VEGFR2]). The cell linings of these structures showed ultrastructural evidence of endothelial differentiation. The neovascular proliferation occurred primarily in the outer aspects of aortic rings, thus suggesting that the new vessels mainly arose from immature endothelial precursor cells localized in the outer layer of the aortic stroma, ie, a process of vasculogenesis rather than angiogenesis. The undifferentiated mesenchymal cells (CD34+/CD31-), isolated and cultured on collagen-fibronectin, differentiated into endothelial cells expressing GD31 and VWF. Furthermore, the CD34+/CD31+ cells were capable of forming a network of capillary-like structures when cultured on Matrigel. This is the first reported study showing the ex vivo formation of human microvessels by vasculogenesis. Our findings indicate that the human embryonic aorta is a rich source of CD34+/CD31- endothelial progenitor cells (angioblasts), and this information may prove valuable in studies of vascular regeneration and tissue bioengineering. C1 Ist Nazl Neurol C Besta, I-20133 Milan, Italy. Univ Brescia, Microbiol Lab, Brescia, Italy. Civic Hosp, Ctr Scompenso Cardiaco, Brescia, Italy. San Raffaele Hosp & Sci Inst, Dept Pathol, Milan, Italy. Inst Obstet & Gynaecol L Mangiagalli, Milan, Italy. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Parati, E (reprint author), Ist Nazl Neurol C Besta, Via Celoria 11, I-20133 Milan, Italy. RI Parati, Eugenio/G-8765-2011; Cova, Lidia/K-6459-2016 OI Cova, Lidia/0000-0002-1504-1556 FU NHLBI NIH HHS [HL52585] NR 24 TC 55 Z9 63 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 2001 VL 81 IS 6 BP 875 EP 885 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 443JM UT WOS:000169338100009 PM 11406648 ER PT J AU Wang, MB Yip, HT Srivatsan, ES AF Wang, MB Yip, HT Srivatsan, ES TI Antisense cyclin D1 enhances sensitivity of head and neck cancer cells to cisplatin SO LARYNGOSCOPE LA English DT Article DE antisense cyclin D1; cisplatin; head and neck cancer ID CHROMOSOME 11Q13 AMPLIFICATION; POOR-PROGNOSIS; DRUG-RESISTANCE; CROSS-LINKS; IN-VITRO; CARCINOMA; INHIBITION; RAS; EXPRESSION; GROWTH AB Objectives: Cyclin D1 is a cell cycle regulatory factor that modulates a critical step in cell cycle control. Cyclin DI is overexpressed in a significant proportion of head and neck cancers and correlates with a poor prognosis, Abrogation of cyclin D1 action through antisense cyclin DI shows promise as an antitumor therapy, with an inhibitory effect in head and neck squamous cell carcinoma both in vitro and in vivo, The suppressive effect of antisense cyclin DI in head and neck cancer xenografts in nude mice is incomplete, however, suggesting that combination with another antitumor agent is necessary for complete tumor eradication. Cisplatin is a widely used chemotherapeutic agent in head and neck cancer, and is particularly effective in combination with radiation therapy, In this study, we investigate whether antisense cyclin D1 enhances the sensitivity of head and neck cancer cells to cisplatin, Such an enhancement of sensitivity mould suggest that combination therapy using antisense cyclin D1 and cisplatin would be an effective treatment modality far head and neck. cancer. Study Design: Antisense cyclin DI was transfected into the head and neck squamous cell carcinoma cell line CCL23 using a plasmid vector, Both the parental CCL23 cells and the antisense cyclin D1-transfected C(CCL23 cells (CCL23AS) were treated with cisplatin at increasing concentrations, The dosage of cisplatin ranged from 1 mug/mL to 10 mug/mL. Initial exposure to cisplatin was for 2 hours, with increasing exposure times in succeeding experiments, Cell viability assays were done following cisplatin exposure. Dose response curves for the two cell lines were plotted and compared. Western blot analyses were done on the cisplatin-treated cell lines to determine levels of cyclin DI expression. Results: Increasing concentrations of cisplatin resulted in significantly higher rates of cell killing in the antisense cyclin D1-transfected cells than in the parental cells. The ID50 values for the parental CCL23 cells and the antisense cyclin D1-transfected CCL23 cells were 7 mug/mL and 3 mug/mL, respectively, indicating significant enhancement of sensitivity to cisplatin in the antisense cyclin D1-transfected cells, Western blot analyses demonstrated decreased expression of cyclin D1 in the CCL23AS cells with increasing doses of cisplatin, compared with the parental CCL23 cells. Conclusions: Antisense cyclin D1-transfected CCL23 cells demonstrate an enhanced sensitivity to the effects of cisplatin compared with the parental cell Line. Although the mechanism for this phenomenon is not completely understood, the data suggests the potential use of combination therapy using antisense cyclin D1 and cisplatin for head and neck cancers. While neither agent alone can completely eradicate head and neck cancers, the synergistic effect of the two may be an effective therapeutic protocol for refractory head and neck cancers. Future investigation into the combination of antisense cyclin D1 with cisplatin for treatment of head and neck cancer is needed. C1 Univ Calif Los Angeles, Div Head & Neck Surg, Sch Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, Div Head & Neck Surg, Sch Med, CHS 62-132,10833 LeConte Ave, Los Angeles, CA 90095 USA. NR 39 TC 18 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD JUN PY 2001 VL 111 IS 6 BP 982 EP 988 DI 10.1097/00005537-200106000-00010 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 439GR UT WOS:000169102900009 PM 11404608 ER PT J AU Fonseca, R Oken, MM Harrington, D Bailey, RJ Van Wier, SA Henderson, KJ Kay, NE Van Ness, B Greipp, PR Dewald, GW AF Fonseca, R Oken, MM Harrington, D Bailey, RJ Van Wier, SA Henderson, KJ Kay, NE Van Ness, B Greipp, PR Dewald, GW TI Deletions of chromosome 13 in multiple myeloma identified by interphase FISH usually denote large deletions of the q arm or monosomy SO LEUKEMIA LA English DT Article DE multiple myeloma; chromosome deletion; paraproteinemias; in situ hybridization ID CHRONIC LYMPHOCYTIC-LEUKEMIA; IN-SITU HYBRIDIZATION; COMPARATIVE GENOMIC HYBRIDIZATION; PLASMA-CELL LEUKEMIA; CYTOGENETIC ABNORMALITIES; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; GENETIC INSTABILITY; 13Q14; TRANSLOCATIONS AB Deletions of the long arm of chromosome 13 (13q-) are observed in patients with multiple myeloma (MM), are rarely observed in the monoclonal gammopathy of undetermined significance (MGUS) and have been associated with a worsened prognosis in MM. However, no minimally deleted region in the 13q arm has been defined at 13q, and consequently no tumor suppressor genes have yet been identified that are important for disease pathogenesis. We attempted to characterize these chromosome 13q deletions at the molecular cytogenetic level. We studied 351 newly diagnosed patients, entered into the E9486/E9487 clinical study of the Eastern Cooperative Oncology Group. Fluorescent in situ hybridization (FISH) combined with immune fluorescent detection (clg-FISH) of clonal plasma cells (PC) and cytomorphology were used to analyze interphase, bone marrow (BM) cell, cytospin slides. We simultaneously used DNA probes for the following locus specific probes (LSI); LSI 13 (Rb) and D13S319, which hybridize to 13q14. We subsequently studied distal deletions using the D13S25 probe (13q14.3) and a subtelomeric probe (13qSTP) for the 13q-arm (D13S327) in 40 cases with documented LSI 13 (Rb)/D13S319 deletion and 40 without deletion of these loci. Of 325 evaluable patients, we found 13q deletions in 176 (54%) using LSI 13 (Rb) and D13S319 probes. Of 40 patients with LSI 13(Rb)/D13S319 deletions, 34 (85%) had coexistent deletion of both D13S25/13qSTP. These results indicate that chromosome 13 deletions in MM involve loss of most if not all of the 13q arm perhaps even indicating monosomy. In six cases the 13qSTP signal was conserved, but D13S25 was lost indicating large interstitial deletions involving 13q14. In 39 of the 40 cases without LSI 13 (Rb)/D13S319 deletions, the normal pattern of two pairs of signals was observed for D13S25/13qSTP. Deletions involving 13q14 are very common in MM as detected by clg-FISH. These deletions appear to predominantly involve loss of large segments of the 13q arm or monosomy 13, and only occasionally represent an interstitial deletion. C1 Mayo Clin, Dept Hematol & Internal Med, Dept Lab Med & Pathol, Minneapolis, MN USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Dana Farber Canc Inst, ECOG Stat Ctr, Boston, MA 02115 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. RP Fonseca, R (reprint author), Div Hematol & Internal Med, Mayo Bldg W10B, Rochester, MN 55905 USA. OI Fonseca, Rafael/0000-0002-5938-3769 FU NCI NIH HHS [CA21115-25C, P01 CA62242, R01 CA83724-01] NR 35 TC 85 Z9 90 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2001 VL 15 IS 6 BP 981 EP 986 DI 10.1038/sj.leu.2402125 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 441DA UT WOS:000169214700017 PM 11417487 ER PT J AU Marshall, D Simpson, KN Earle, CC Chu, CW AF Marshall, D Simpson, KN Earle, CC Chu, CW TI Potential cost-effectiveness of one-time screening for lung cancer (LC) in a high risk cohort SO LUNG CANCER LA English DT Article DE cost-effectiveness analysis; lung cancer screening; helical computed-tomography; Early Lung Cancer Action Project ID DIAGNOSIS; SURVIVAL; PROJECT; STAGE AB The development of low-dose helical computed-tomography (CT) scanning to detect nodules as small as a few mm has sparked renewed interest in lung cancer (LC) screening. The objective of this study was to assess the potential health effects and cost-effectiveness of a one-time low-dose helical CT scan to screen for LC. We created a decision analysis model using baseline results from the Early Lung Cancer Action Project (ELCAP); Surveillance, Epidemiology and End Results (SEER) registry public-use database: screening program costs estimated from 1999 Medicare reimbursement rates: and annual costs of managing cancer and non-cancer patients from Riley et al. (1995) [Med Care 1995:33(8):828-841] and Taplin et al. (1995) [J Nail Cancer Inst 1995:87(6):417-26], The main outcome measures included years of life, cost estimates of baseline diagnostic screening and Follow up, and cost-effectiveness of screening. We found that in a very high-risk cohort (LC prevalence of 2.7%) of patients between 60 and 74 years of age. a one-time screen appears to be cost-effective at $5940 per life year saved. In a lower risk general population of smokers (LC prevalence of 0.7%), a one-time screen appears to be cost-effective at $23 100 per life year. Even when a lead-time bias of 1 year is incorporated into the model for a low risk population, the cost-effectiveness is estimated at $58 183 per life year. Based on the assumptions embedded in this model, one-time screening of elderly high-risk patients for LC appears to be cost-effective. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Bayer Diagnost, Emeryville, CA USA. Med Univ S Carolina, Charleston, SC 29425 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Marshall, D (reprint author), McMaster Univ, St Josephs Hosp, Ctr Evaluat Med, 50 Charlton Ave,E H-304, Hamilton, ON L8N 4A6, Canada. RI Marshall, Deborah/J-7248-2015 OI Marshall, Deborah/0000-0002-8467-8008 NR 30 TC 52 Z9 52 U1 0 U2 4 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 JUN PY 2001 VL 32 IS 3 BP 227 EP 236 DI 10.1016/S0169-5002(00)00239-7 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 441ZX UT WOS:000169260400002 PM 11390004 ER PT J AU Skarin, AT Herbst, RS Leong, TL Bailey, A Sugarbaker, D AF Skarin, AT Herbst, RS Leong, TL Bailey, A Sugarbaker, D TI Lung cancer in patients under age 40 SO LUNG CANCER LA English DT Article DE lung cancer; lung cancer under age 40; adenocarcinoma; squamous cell carcinoma; small cell lung cancer; large cell lung cancer ID YOUNG-ADULTS; BRONCHOGENIC-CARCINOMA; RISK-FACTORS; SMOKING AB A retrospective review of patients < 40 years (n = 91) seen at the Dana-Farber Cancer Institute and Brigham and Women's Hospital from January I, 1983-January 1, 1993 was carried out. Of 91 patients, there were 43 men and 48 women with a median age of 36 years (range 28-39). Eighty percent of patients were cigarette smokers for a tnedian of 25 pack years (range 2-68). Ninety-one percent were symptomatic at presentation. The ECOG performance status (PS) was 0 or 1 in 83%.. At the time of diagnosis 15% had stage I/II, 17% stage IIIA, 22% stage IIIB and 45% stage IV disease. The most common histopathology was adenocarcinoma (46%). followed by small cell carcinoma (14%) squamous cell carcinoma (12%), large cell undifferentiated (8%) and other types (20%). The median survival for all 91 patients was 1 year with 2 and 5 year survivals of 30% and 18% respectively. Five year survival was related to stage of disease: 60% for patients with stage I. 58%, for stage II. 36% for stage IIIA, 10% L for stags 111B, and 3% for stage IV disease. Factors that had no significant effect on overall survival included gender, histologic subtype. degree of differentiation, presence or absence of symptoms, and sites of metastases. Factors that adversely affected survival by univariate analysis included advanced stage of disease, poor PS. duration of symptoms for more than 3 months, and 5% or greater body weight loss. By multivariate analysis only stage (P < 0.001) and weight loss (P = 0.02) affected survival. This data plus results of other published studies show that young patients under age 40 with lung cancer. compared to the more common older patients, have an increased percentage of women, have a longer duration of symptoms, more often have adenocarcinoma with lower frequency of squamous cell carcinoma and sometimes small cell carcinoma, and more often present with advanced disease. Despite these differences, overall patient survival remains poor and is similar to that of older patients. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, 75 Francis St, Boston, MA 02115 USA. EM arthur_skarin@dfci.harvard.edu NR 37 TC 32 Z9 46 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 EI 1872-8332 J9 LUNG CANCER JI Lung Cancer PD JUN PY 2001 VL 32 IS 3 BP 255 EP 264 DI 10.1016/S0169-5002(00)00233-6 PG 10 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 441ZX UT WOS:000169260400005 PM 11390007 ER PT J AU Sachs, RK Hlatky, LR Hahnfeldt, P AF Sachs, RK Hlatky, LR Hahnfeldt, P TI Simple ODE models of tumor growth and anti-angiogenic or radiation treatment SO MATHEMATICAL AND COMPUTER MODELLING LA English DT Article DE radiotherapy and chemotherapy; tumor growth kinetics; angiogenic inhibitors; time factors ID LINEAR-QUADRATIC MODEL; MATHEMATICAL-MODELS; DIFFUSION-MODEL; CELL-SURVIVAL; REPAIR MODEL; RADIOTHERAPY; PARAMETERS; CANCER; REDISTRIBUTION; FORMULATION AB Models of tumor growth and treatment based on one or two ordinary differential equations are heavily used in practice because they are simple but can often still capture the essence of complicated interactions. Currently relevant examples of such models are given here: some classic growth equations, an ODE pair for the interplay between tumor and neovascularization during cancer growth or therapy, and an ODE pair for response to ionizing radiation. Mathematically more sophisticated generalizations of various kinds, usually more realistic but less practical, are mentioned very briefly. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, DFCI, Boston, MA 02115 USA. RP Sachs, RK (reprint author), Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. EM sachs@math.berkeley.edu NR 57 TC 96 Z9 99 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-7177 J9 MATH COMPUT MODEL JI Math. Comput. Model. PD JUN PY 2001 VL 33 IS 12-13 BP 1297 EP 1305 DI 10.1016/S0895-7177(00)00316-2 PG 9 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA 431DE UT WOS:000168615900009 ER PT J AU Parmigiani, G Skates, S AF Parmigiani, G Skates, S TI Estimating distribution of the age of onset of detectable asymptomatic cancer SO MATHEMATICAL AND COMPUTER MODELLING LA English DT Article DE deconvolution; breast cancer screening; preclinical cancer ID BREAST-CANCER; NATURAL-HISTORY; DISEASE; DURATION; TIME AB In this paper, we develop a model and a deconvolution technique to estimate the distribution of the age of onset of detectable preclinical cancer, using incidence data and information about cancer growth rate. Our approach considers the effect of age on both the growth rate and competing causes of death. We illustrate our methodology using data on breast cancer, and discuss implications for breast cancer screening. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Biostat, Baltimore, MD 21205 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Parmigiani, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, 550 N Broadway,Suite 1103, Baltimore, MD 21205 USA. NR 32 TC 6 Z9 6 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-7177 J9 MATH COMPUT MODEL JI Math. Comput. Model. PD JUN PY 2001 VL 33 IS 12-13 BP 1347 EP 1360 DI 10.1016/S0895-7177(00)00320-4 PG 14 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Mathematics, Applied SC Computer Science; Mathematics GA 431DE UT WOS:000168615900013 ER PT J AU Ntziachristos, V Chance, B AF Ntziachristos, V Chance, B TI Accuracy limits in the determination of absolute optical properties using time-resolved NIR spectroscopy SO MEDICAL PHYSICS LA English DT Article DE NIR spectroscopy; time-resolved measurements; sensitivity analysis; temporal resolution ID NEAR-INFRARED SPECTROSCOPY; BOUNDARY-CONDITIONS; TISSUE; REFLECTANCE; INSTRUMENT AB We assess typical systematic experimental errors involved in a time-resolved measurement as applied to NIR diffuse optical spectroscopy and investigate their effect on the quantification accuracy of the absorption and the reduced scattering coefficient. We demonstrate that common systematic experimental uncertainties may lead to quantification errors of 10% or more, even when excellent. signal to noise ratio conditions exist and accurate photon propagation models are employed. We further demonstrate that the accuracy of the calculation depends nonlinearly on the optical properties of the medium measured. High scattering and low absorbing media can be quantified more accurately than media with low scattering or high absorption using measurements of the same signal to noise ratio. We further discuss curve-shape fitting schemes that aid in improving the quantification accuracy in the presence of experimental errors. Finally, we identify uncertainties that set quantification accuracy limits and we find temporal resolution as the ultimate limiting factor in the quantification accuracy achieved. Our findings suggest that temporal resolution of the order of 10 ps is necessary for quantifying the absorption and reduced scattering coefficient of diffuse media with accuracy better than 5% using curve fitting methods. In that sense this analysis can be used in time-resolved system design and in predicting the expected errors given the technology selected for time-resolved measurements. (C) 2001 American Association of Physicists in Medicine. C1 Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Univ Penn, Dept Biochem Biophys, Philadelphia, PA 19104 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149 13th St 5406, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA60182] NR 23 TC 50 Z9 50 U1 0 U2 6 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2001 VL 28 IS 6 BP 1115 EP 1124 DI 10.1118/1.1373674 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 445DU UT WOS:000169443500026 PM 11439481 ER PT J AU Harada, ND Chiu, V King, AC Stewart, AL AF Harada, ND Chiu, V King, AC Stewart, AL TI An evaluation of three self-report physical activity instruments for older adults SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE measurement; aging; exercise ID HEALTH SURVEY SF-36; ACTIVITY SCALE; ELDERLY PASE; ZUTPHEN; FATNESS; QUALITY; INDEX AB Purpose: To assess the known-groups and construct validity of measures from the CHAMPS Physical Activity Questionnaire, Physical Activity Survey for the Elderly BASE), and the Yale. Physical Activity Survey (YPAS). Methods: The three questionnaires were administered to a convenience sample of older adults (N = 87) recruited from community centers and retirement homes. Validation measures included the SF-36 measures of physical Functioning general health, mental health, and pain; body mass index; performance-based tests of lower body functioning and endurance; and Mini-Logger activity monitor data from ankle and waist sensors. Validity was estimated by testing hypotheses about associations between physical activity and validation measures. Results: As hypothesized, differences in activity levels on all measures were found between older adults in retirement homes (less active) and community centers (more active) (P-values < 0.0001). Correlations of physical activity measures with performance-based measures ranged from 0.44 to 0.68, conforming to hypotheses; hypotheses regarding associations with the SF-36 measures were also confirmed. Body mass index was not correlated with any of the physical activity measures, contrary to hypotheses. Correlations of physical activity measures with Mini-Logger counts ranged from 0.36 to 0.59 (ankle) and 0.42 to 0.61 (waist) as hypothesized. Correlations among the measures from the three instruments ranged from 0.58 to 0.68. Conclusions: The PASE, YPAS, and CHAMPS each demonstrated acceptable validity, as all measures met nearly all hypotheses. Higher validity coefficients were found for subgroups (men, 65-74 yr, retirement home), suggesting that these instruments may perform better for certain segments of the older adult population. C1 VA Greater Los Angeles Healthcare Syst, GRECC 11G, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, UCLA VA RAND MEDTEP Ctr, Los Angeles, CA USA. Stanford Univ, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94143 USA. RP Harada, ND (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC 11G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIA NIH HHS [AG09931] NR 29 TC 256 Z9 263 U1 4 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JUN PY 2001 VL 33 IS 6 BP 962 EP 970 DI 10.1097/00005768-200106000-00016 PG 9 WC Sport Sciences SC Sport Sciences GA 439UL UT WOS:000169135900016 PM 11404662 ER PT J AU Tatlidil, R Mandelkern, M AF Tatlidil, R Mandelkern, M TI FDG-PET in the detection of gastrointestinal metastases in melanoma SO MELANOMA RESEARCH LA English DT Article DE FDG; melanoma; PET ID POSITRON-EMISSION-TOMOGRAPHY; MALIGNANT-MELANOMA; TRACT; MANAGEMENT AB We report six cases of malignant melanoma metastatic to the small bowel in which the information obtained from fluorodeoxyglucose positron emission tomography (FDG-PET) contributed significantly to the management of the patients. In each of these cases the conventional diagnostic work-up missed findings that were important for treatment planning. We conclude that FDG-PET is a valuable modality in melanoma patients with suspected gastrointestinal involvement. It is also a sensitive technique for the diagnosis of other intra-abdominal as well as extra-abdominal metastases. (C) 2001 Lippincott Williams & Wilkins. C1 VA Greater Los Angeles Hlth Care Syst, Dept Nucl Med, Los Angeles, CA USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92717 USA. RP Tatlidil, R (reprint author), 1362 Sokak 14-A, TR-35230 Izmir, Turkey. NR 13 TC 11 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD JUN PY 2001 VL 11 IS 3 BP 297 EP 301 DI 10.1097/00008390-200106000-00012 PG 5 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 445ZX UT WOS:000169489400012 PM 11468519 ER PT J AU Proctor, SP Harley, R Wolfe, J Heeren, T White, RF AF Proctor, SP Harley, R Wolfe, J Heeren, T White, RF TI Health-related quality of life in Persian Gulf War veterans SO MILITARY MEDICINE LA English DT Article ID OF-LIFE; MEDICAL CONDITIONS; SURVEY SF-36; QUESTIONNAIRE; STRESS; CARE; ILLNESSES; RELIABILITY; AGREEMENT; OUTCOMES AB Objective: The objective of this investigation is to describe the health-related quality of life of Persian Gulf War (GW) veterans and to examine the effects of current chronic medical conditions and psychiatric status on physical functioning. Methods: To measure health-related quality of life, the Medical Outcomes Short Form Survey (SF36) was administered approximately 4 years after the GW to a stratified, random sample of New England-area GW-deployed veterans and a group of military personnel deployed to Germany during the GW. The SF36 scores for the GW-deployed study population (N = 141) were compared with those for the Germany-deployed group [N = 46) and with published U.S. population norms. Multiple linear regression analyses were performed to identify risk factors associated with lower physical health functioning in the GW-deployed study group. Results: Functional health status was significantly lower in the GW-deployed group compared with the Germany-deployed group for each of the SP36 subscales and the two summary scores (Physical Component Summary [PCS] and Mental Component Summary). Compared with the general U.S. population, the GW-deployed group median was between the 25th and 50th percentile for the Physical Functioning subscale and the PCS score. Within the GW-deployed group, lower education, psychological symptomatology, and a higher number of chronic self-reported medical conditions were significant predictors of the PCS score. Conclusion: GW-deployed veterans report lower functional health status compared with a group of Germany-deployed veterans and published general U.S. population norms. Within the group of GW-deployed veterans, several current medical and psychological conditions predictive of lower physical functioning levels were identified. C1 VA Boston Healthcare Syst, Boston Environ Hazards Ctr, Boston, MA USA. VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Odense Univ, Dept Environm Med, Odense, Denmark. RP Proctor, SP (reprint author), VA Boston Healthcare Syst, Boston Environ Hazards Ctr, Boston, MA USA. NR 58 TC 26 Z9 32 U1 1 U2 1 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUN PY 2001 VL 166 IS 6 BP 510 EP 519 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 653DC UT WOS:000181419100012 PM 11413729 ER PT J AU Johansen, LM Iwama, A Lodie, TA Sasaki, K Felsher, DW Golub, TR Tenen, DG AF Johansen, LM Iwama, A Lodie, TA Sasaki, K Felsher, DW Golub, TR Tenen, DG TI C-Myc is a critical target for C/EBP alpha in granulopoiesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BINDING-PROTEIN-ALPHA; STIMULATING FACTOR-RECEPTOR; RNA INHIBITS PROLIFERATION; TRANSCRIPTION FACTOR PU.1; GENE-EXPRESSION; DNA-BINDING; MYELOID-LEUKEMIA; CELL-GROWTH; IN-VIVO; ADIPOCYTE DIFFERENTIATION AB CCAAT/enhancer binding protein alpha (C/EBP alpha) is an integral factor in the granulocytic developmental pathway, as myeloblasts from C/EBP alpha -null mice exhibit an early block in differentiation. Since mice deficient for known C/EBP alpha target genes do not exhibit the same block in granulocyte maturation, we sought to identify additional C/EBP alpha target genes essential for myeloid cell development. To identify such genes, we used both representational difference analysis and oligonucleotide array analysis with RNA derived from a C/EBP alpha -inducible myeloid cell line. From each of these independent screens, we identified c-Myc as a C/EBP alpha negatively regulated gene. We mapped an E2F binding site in the c-Myc promoter as the cis-acting element critical for C/EBP alpha negative regulation. The identification of c-Myc as a C/EBP alpha target gene is intriguing, as it has been previously shown that down-regulation of c-Myc can induce myeloid differentiation. Here we show that stable expression of c-Myc from an exogenous promoter not responsive to C/EBP alpha -mediated down-regulation forces myeloblasts to remain in an undifferentiated state. Therefore, C/EBP alpha negative regulation of c-Myc is critical for allowing early myeloid precursors to enter a differentiation pathway. This is the first report to demonstrate that C/EBP alpha directly affects the level of c-Myc expression and, thus, the decision of myeloid blasts to enter into the granulocytic differentiation pathway. C1 Harvard Univ, Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Tsukuba, Dept Immunol, Tsukuba, Ibaraki 305, Japan. Stanford Univ, Sch Med, Stanford, CA USA. RP Tenen, DG (reprint author), Harvard Univ, Inst Med, Room 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL056745, HL56745]; NIDDK NIH HHS [F32 DK009892, F32DK09892] NR 75 TC 170 Z9 179 U1 0 U2 4 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 JUN PY 2001 VL 21 IS 11 BP 3789 EP 3806 DI 10.1128/MCB.21.11.3789-3806.2001 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 432QF UT WOS:000168706600017 PM 11340171 ER PT J AU Belyamani, M Gangolli, EA Idzerda, RL AF Belyamani, M Gangolli, EA Idzerda, RL TI Reproductive function in protein kinase inhibitor-deficient mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID A MUTANT MICE; CATALYTIC SUBUNIT; GENE-EXPRESSION; BETA-ISOFORMS; MOUSE SPERM; RAT TESTIS; ALPHA; MOTILITY; MONOPHOSPHATE; CAPACITATION AB The protein kinase inhibitor (PKI) family includes three genes encoding small, heat-stable inhibitors of the cyclic AMP-dependent kinase PKA. Each PKI isoform contains a PKA inhibitory domain and a nuclear export domain, enabling PKI to both inhibit PKA and remove it from the nucleus. The PKI beta isoform, also known as testis PKI, is highly expressed in germ cells of the testis and is found at more modest levels in other tissues. In order to investigate its physiological role, we have generated PKI beta knockout mice by gene targeting. These mice exhibit a partial loss of PKI activity in testis but remain fertile with normal testis development and function. PKI beta knockout females also reproduce normally. The PKI beta mutants were crossed,vith our previously derived PKI alpha mutants to obtain double-knockout mice. Remarkably, these mice are also viable and fertile with no obvious physiological defects in either males or females. C1 Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Idzerda, RL (reprint author), Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Box 357138, Seattle, WA 98195 USA. FU NICHD NIH HHS [HD 33057]; NIDDK NIH HHS [T32 DK07247, T32 DK007247] NR 24 TC 8 Z9 8 U1 0 U2 0 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 JUN PY 2001 VL 21 IS 12 BP 3959 EP 3963 DI 10.1128/MCB.21.12.3959-3963.2001 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 436XY UT WOS:000168962200010 PM 11359903 ER PT J AU Suominen, L Roos, C Lortet, G Paulin, L Lindstrom, K AF Suominen, L Roos, C Lortet, G Paulin, L Lindstrom, K TI Identification and structure of the Rhizobium galegae common nodulation genes: Evidence for horizontal gene transfer SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE legumes; Rhizobium; phylogeny; nodulation genes; host constraint ID TRANSPOSON TN5 MUTAGENESIS; HOST-SPECIFICITY; NUCLEOTIDE-SEQUENCE; SIGNAL MOLECULES; PLANT-SIGNAL; DNA-SEQUENCE; FATTY-ACIDS; NOD FACTORS; MELILOTI; BACTERIA AB Rhizobia are soil bacteria able to fix atmospheric nitrogen in symbiosis with leguminous plants. In response to a signal cascade coded by genes of both symbiotic partners, a specific plant organ, the nodule, is formed. Rhizobial nodulation (nod) genes trigger nodule formation through the synthesis of Nod factors, a family of chitolipooligo-saccharides that are specifically recognized by the host plant at the first stages of the nodulation process. Here, we present the organization and sequence of the common nod genes from Rhizobium galegae, a symbiotic member of the Rhizobiaceae. This species has an intriguing phylogenetic position, being symbiotic among pathogenic agrobacteria, which induce tumors instead of nodules in plant shoots or roots. This apparent incongruence raises special interest in the origin of the symbiotic apparatus of R. galegae. Our analysis of DNA sequence data indicated that the organization of the common nod gene region of R. galegae was similar to that of Sinorhizobium meliloti and Rhizobium leguminosarum, with nodIJ downstream of nodABC and the regulatory nodD gene closely linked to the common nod operon. Moreover, phylogenetic analyses of the nod gene sequences showed a close relationship especially between the common nodA sequences of R. galegae, S. meliloti, and R. leguminosarum biovars viciae and trifolii. This relationship in structure and sequence contrasts with the phylogeny based on 16S rRNA, which groups R. galegae close to agrobacteria and separate from most other rhizobia. The topology of the nodA tree was similar to that of the corresponding host plant tree. Taken together, these observations indicate that lateral nod gene transfer occurred from fast-growing rhizobia toward agrobacteria, after which the symbiotic apparatus evolved under host plant constraint. C1 Univ Helsinki, Bioctr 1, Div Microbiol, Dept Appl Chem & Microbiol, FIN-00014 Helsinki, Finland. Univ Helsinki, Inst Biotechnol, FIN-00014 Helsinki, Finland. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Suominen, L (reprint author), Univ Helsinki, Bioctr 1, Div Microbiol, Dept Appl Chem & Microbiol, POB 56, FIN-00014 Helsinki, Finland. EM leena.suominen@helsinki.fi NR 69 TC 42 Z9 44 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUN PY 2001 VL 18 IS 6 BP 907 EP 916 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 440MZ UT WOS:000169180200002 PM 11371578 ER PT J AU Scheuner, D Song, BB McEwen, E Liu, C Laybutt, R Gillespie, P Saunders, T Bonner-Weir, S Kaufman, RJ AF Scheuner, D Song, BB McEwen, E Liu, C Laybutt, R Gillespie, P Saunders, T Bonner-Weir, S Kaufman, RJ TI Translational control is required for the unfolded protein response and in vivo glucose homeostasis SO MOLECULAR CELL LA English DT Article ID WOLCOTT-RALLISON-SYNDROME; ENDOPLASMIC-RETICULUM; TRANSMEMBRANE PROTEIN; MOLECULAR MECHANISMS; REGULATED PROTEINS; STRESS-RESPONSE; MESSENGER-RNA; C/EBP-ALPHA; KINASE; CELLS AB The accumulation of unfolded protein in the endoplasmic reticulum (ER) attenuates protein synthesis initiation through phosphorylation of the cu subunit of eukaryotic translation initiation factor 2 (eIF2 alpha) at Ser51. Subsequently, transcription of genes encoding adaptive functions including the glucose-regulated proteins is induced. We show that eIF2 alpha. phosphorylation is required for translation attenuation, transcriptional induction, and survival in response to ER stress. Mice with a homozygous mutation at the eIF2 alpha phosphorylation site (Ser51Ala) died within 18 hr after birth due to hypoglycemia associated with defective gluconeogenesis. In addition, homozygous mutant embryos and neonates displayed a deficiency in pancreatic P cells. The results demonstrate that regulation of translation through eIF2 alpha phosphorylation is essential for the ER stress response and in vivo glucose homeostasis. C1 Univ Michigan, Med Ctr, Dept Biol Chem, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Transgen Anim Model Core, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kaufman, RJ (reprint author), Univ Michigan, Med Ctr, Dept Biol Chem, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Liu, Andrew/B-3548-2009 OI Liu, Andrew/0000-0003-1927-0900 FU NIAID NIH HHS [AI 42394] NR 51 TC 778 Z9 791 U1 2 U2 24 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JUN PY 2001 VL 7 IS 6 BP 1165 EP 1176 DI 10.1016/S1097-2765(01)00265-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 447AY UT WOS:000169547400005 PM 11430820 ER PT J AU Pru, JK Tilly, JL AF Pru, JK Tilly, JL TI Programmed cell death in the ovary: Insights and future prospects using genetic technologies SO MOLECULAR ENDOCRINOLOGY LA English DT Review ID MESSENGER-RIBONUCLEIC-ACID; DOUBLE-STRANDED-RNA; CORPUS-LUTEUM; CASPASE ACTIVATION; OOCYTE APOPTOSIS; CRE RECOMBINASE; GRANULOSA-CELLS; FAMILY MEMBERS; MOUSE OOCYTES; CYTOCHROME-C AB Programmed cell death (PCD) plays a prominent role in development of the fetal ovaries and in the postnatal ovarian cycle. As is the case with other major organ systems, an evolutionarily conserved framework of genes and signaling pathways has been implicated in determining whether or not ovarian germ cells and somatic cells will die in response to either developmental cues or pathological insults. However, the identification of increasing numbers of potential ovarian cell death regulatory factors over the past several years has underscored the need for studies to now separate correlation (e.g. endogenous gene expression) from function (e.g. requirement of the gene product for the execution of PCD). In this regard, genetic technologies have recently been used to examine the functional significance of specific proteins and signaling molecules to the regulation of PCD in the female gonad in vivo. In addition to the more classic approaches, such as the use of genetic null and transgenic mice, methods that achieve cell lineage-selective and/or developmentally timed gene targeting are on the horizon for use by reproductive biologists to more accurately dissect the mechanisms by which PCD is controlled in the ovary. This minireview will highlight some of the advances that have already been made using gene knockout and transgenic mice, as well as provide an overview of the current and future status of cell lineage-selective gene disruption, in the context of PCD and ovarian function. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Vincent Ctr Reprod Biol, Dept Obstet & Gynecol, VBK137C-GYN,55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG-12279]; NICHD NIH HHS [R01-HD-34226]; NIEHS NIH HHS [R01-ES-08430] NR 81 TC 70 Z9 72 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2001 VL 15 IS 6 BP 845 EP 853 DI 10.1210/me.15.6.845 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436GR UT WOS:000168928600001 PM 11376105 ER PT J AU Clarke, TR Hoshiya, Y Yi, SE Liu, XH Lyons, KM Donahoe, PK AF Clarke, TR Hoshiya, Y Yi, SE Liu, XH Lyons, KM Donahoe, PK TI Mullerian inhibiting substance signaling uses a bone morphogenetic protein (BMP)-like pathway mediated by ALK2 and induces Smad6 expression SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TGF-BETA SIGNALS; II RECEPTOR; DEVELOPMENTAL EXPRESSION; MOUSE EMBRYOGENESIS; MESENCHYMAL CELLS; GENETIC-ANALYSIS; DUCT REGRESSION; MESSENGER-RNA; HOMEOBOX GENE; LEYDIG-CELLS AB Signal reception of Mullerian inhibiting substance (MIS) in the mesenchyme around the embryonic Mullerian duct in the male is essential for regression of the duct. Deficiency of MIS or of the MIS type II receptor, MISRII, results in abnormal reproductive development in the male due to the maintenance of the duct. MIS is a member of the transforming growth factor-beta (TGF beta) superfamily of secreted protein hormones that signal through receptor complexes of type I and type II serine/threonine kinase receptors. To investigate candidate MIS type I receptors, we examined reporter construct activation by MIS. The bone morphogenetic protein (BMP)-responsive Tlx2 and Xvent2 promoter-driven reporter constructs were stimulated by MIS but the TGF beta /activin-induced p3TP-lux or CAGA-luc reporter constructs were not. The induction of Tlx2-luc was dependent upon the kinase activity of MISRII and was blocked by a dominant negative truncated ALK2 (tALK2) receptor but not by truncated forms of the other BMP type I receptors ALK1, ALK3, or ALK6. MIS induced activation of a Gal4DBD-Smad1 but not a Gal4DBD-Smad2 fusion protein. This activation could also be blocked by tALK2. The BMP-induced inhibitory Smad, Smad6, was up-regulated by MIS endogenously in Leydig cell-derived lines and is expressed in male but not female Mullerian duct mesenchyme. ALK6 has been shown to function as an MIS type I receptor. Investigation of the pattern of ALK2, MISRII, and ALK6 in the developing urogenital system demonstrated overlapping expression of ALK2 and MISRII in the mesenchyme surrounding the duct while ALK6 was observed only in the epithelium. Examination of ALK6-/- male animals revealed no defect in duct regression. The reporter construct analysis, pattern of expression of the receptors, and analysis of ALK6-deficient animals suggest that ALK2 is the MIS type I receptor involved in Mullerian duct regression. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Orthopaed Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Mol Cellular & Dev Biol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Dept Surg, Warren 11, Boston, MA 02114 USA. RI Lyons, Karen/P-1843-2014 OI Lyons, Karen/0000-0001-9420-5813 FU NCI NIH HHS [CA-17393]; NIAMS NIH HHS [AR-44528, R01 AR044528]; NICHD NIH HHS [HD-32112, HD-28138] NR 72 TC 119 Z9 125 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2001 VL 15 IS 6 BP 946 EP 959 DI 10.1210/me.15.6.946 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 436GR UT WOS:000168928600009 PM 11376113 ER PT J AU Weeks, DL Sachs, G AF Weeks, DL Sachs, G TI Sites of pH regulation of the urea channel of Helicobacter pylori SO MOLECULAR MICROBIOLOGY LA English DT Article ID STREPTOCOCCUS-SALIVARIUS; CAMPYLOBACTER-PYLORI; ACID RESISTANCE; PROTEIN; WATER; TRANSPORTERS; METABOLISM; EXPRESSION; GLYCEROL; OOCYTES AB Helicobacter pylori (Hp) and Streptococcus salivarius (Ss) require intrabacterial urease for acid resistance and express a urea channel, UreI. The presence of UreI was shown to increase urea permeability approximate to 300-fold over that of a non-polar ureI deletion mutant. Expression of SsUreI in Xenopus oocytes increased urea uptake pH independently, whereas HpUreI shows an acidic pH dependence, half-maximal at pH 6.0. Mutagenesis of all histidines, aspartates, glutamates and the lysine in the periplasmic domain of HpUreI showed that His-123, His-131, Asp-129, Asp-140, Glu-138 and Lys-132 in the second periplasmic loop (PL2) and His-193 in the C-terminus (Ct) were important for activation of transport. With the exception of a lysine that was shown to substitute for His-193 in HpUreI, these charged amino acids are absent in SsUreI. A chimera in which PL1 of HpUreI was replaced by PL1 of SsUreI retained activity at acidic pH and gained partial activity at neutral pH. Exchange of PL2 inactivated transport, whereas exchange of Ct had no effect. Chimeras, in which either PL1 or PL2 of HpUreI replaced those of SsUreI, retained wild-type transport, but replacement of the Ct or both loops inactivated transport. PL1 appears to be important for restricting transport through HpUreI at neutral pH, whereas protonation of three histidines in PL2 and Ct and the presence of three dicarboxylic amino acids in PL2 appears to be necessary to activate HpUreI at acidic pH. C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90073 USA. RP Sachs, G (reprint author), VA Greater Los Angeles Hlth Care Syst, Bldg 113,Room 324, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK46917, DK41301, DK17294, DK53462] NR 30 TC 44 Z9 54 U1 1 U2 11 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUN PY 2001 VL 40 IS 6 BP 1249 EP 1259 DI 10.1046/j.1365-2958.2001.02466.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 447NY UT WOS:000169580400002 PM 11442825 ER PT J AU Kucherlapati, R DePinho, RA AF Kucherlapati, R DePinho, RA TI Cancer - Telomerase meets its mismatch SO NATURE LA English DT Editorial Material ID MAINTENANCE; YEAST C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kucherlapati, R (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. NR 11 TC 6 Z9 10 U1 0 U2 1 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN PY 2001 VL 411 IS 6838 BP 647 EP 648 DI 10.1038/35079715 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 439JC UT WOS:000169112500025 PM 11395749 ER PT J AU Ranger, AM Malynn, BA Korsmeyer, SJ AF Ranger, AM Malynn, BA Korsmeyer, SJ TI Mouse models of cell death SO NATURE GENETICS LA English DT Article ID BCL-2 PROTEIN EXPRESSION; FAS-MEDIATED APOPTOSIS; CYTOCHROME-C; DEFICIENT MICE; IN-VIVO; EMBRYONIC LETHALITY; CASPASE ACTIVATION; MURINE DEVELOPMENT; BAX; MITOCHONDRIA AB Cell death is critical for the development and orderly maintenance of cellular homeostasis in metazoans. Developmental genetics in model systems, including Caenorhabditis elegans and Drosophila melanogaster, have helped to identify and order the components of cell-death pathways. An even more complex network of apoptotic pathways has evolved in higher organisms that possess homologs within each set of cell-death regulators. Whereas biochemical studies provide details of molecular mechanisms, genetic models reveal the essential physiologic roles. Transgenic and gene-ablated mice have helped to elucidate mammalian apoptotic pathways and identify the principal effect of each cell death regulator. Here, we review the details of the apoptotic machinery as revealed by mice deficient in critical components of cell-death pathways; we concentrate on cell-death regulators classified as members of the caspase and Bcl2 families or, broadly, as adaptors and mitochondrial released factors. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol & Med, Boston, MA USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Dept Pathol & Med, Boston, MA USA. NR 65 TC 196 Z9 202 U1 0 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 2001 VL 28 IS 2 BP 113 EP 118 DI 10.1038/88815 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 437UK UT WOS:000169011800007 PM 11381252 ER PT J AU Ueki, Y Tiziani, V Santanna, C Fukai, N Maulik, C Garfinkle, J Ninomiya, C doAmaral, C Peters, H Habal, M Rhee-Morris, L Doss, JB Kreiberg, S Olsen, BR Reichenberger, E AF Ueki, Y Tiziani, V Santanna, C Fukai, N Maulik, C Garfinkle, J Ninomiya, C doAmaral, C Peters, H Habal, M Rhee-Morris, L Doss, JB Kreiberg, S Olsen, BR Reichenberger, E TI Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism SO NATURE GENETICS LA English DT Article ID IDENTIFICATION; 4P16.3; MAPS AB Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws(1) followed by development of fibrous tissue masses, which causes a characteristic facial swelling. Here we describe seven mutations in the SH3-binding protein SH3BP2 (MIM 602104) on chromosome 4p16.3 that cause cherubism. C1 Harvard Univ, Sch Med, Harvard Forsyth Dept Oral Biol, Harvard Sch Dent Med, Boston, MA USA. Harvard Univ, Sch Med, Forsyth Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Univ Fed Sao Paulo, EPM, Campinas, SP, Brazil. SOBRAPAR, Inst Cirug Plast Craniofacial, Campinas, SP, Brazil. Humboldt Univ, Inst Med Genet, Sch Med, Berlin, Germany. Tampa Craniofacial Ctr, Tampa, FL USA. Univ Calif Davis, Sacramento, CA 95817 USA. So Maine Oral & Maxillofacial Surg, S Portland, ME USA. Univ Copenhagen, Sch Dent, Dept Pediat Dent, Copenhagen, Denmark. RP Reichenberger, E (reprint author), Harvard Univ, Sch Med, Harvard Forsyth Dept Oral Biol, Harvard Sch Dent Med, Boston, MA USA. FU NIAMS NIH HHS [AR36819, AR36820] NR 8 TC 164 Z9 174 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 2001 VL 28 IS 2 BP 125 EP 126 DI 10.1038/88832 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 437UK UT WOS:000169011800011 PM 11381256 ER PT J AU Sklar, P Schwab, SG Williams, NM Daly, M Schaffner, S Maier, W Albus, M Trixler, M Eichhammer, P Lerer, B Hallmayer, J Norton, N Williams, H Zammit, S Cardno, AG Jones, S McCarthy, G Milanova, V Kirov, G O'Donovan, MC Lander, ES Owen, MJ Wildenauer, DB AF Sklar, P Schwab, SG Williams, NM Daly, M Schaffner, S Maier, W Albus, M Trixler, M Eichhammer, P Lerer, B Hallmayer, J Norton, N Williams, H Zammit, S Cardno, AG Jones, S McCarthy, G Milanova, V Kirov, G O'Donovan, MC Lander, ES Owen, MJ Wildenauer, DB TI Association analysis of NOTCH4 loci in schizophrenia using family and population-based controls SO NATURE GENETICS LA English DT Article ID SUSCEPTIBILITY AB A genetic association between NOTCH4 and schizophrenia has previously been proposed(1). Unsing all markers previously shown to be associated, we found no evidence for such in three independent family-based samples (n=519 parent-offspring trios), and a case-control sample derived from the same ethnic background as the original observaton, These data strongly suggest that NOTCH4 is not a significant susceptibility allele for schizophrenia. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Univ Bonn, Dept Psychiat, Genet Mol Lab, D-53111 Bonn, Germany. Univ Wales Coll Med, Dept Psychol Med, Cardiff CF4 4XN, S Glam, Wales. Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany. Mental State Hosp, D-85529 Haar, Germany. Univ Pecs, Sch Med, Dept Psychiat, H-7623 Pecs, Hungary. Univ Regensburg, Dept Psychiat, D-93042 Regensburg, Germany. Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Psychiat, IL-91120 Jerusalem, Israel. Univ Western Australia, Graylands Hosp, Ctr Clin Res Neuropscyhiat, Mtr Claremont, WA 6010, Australia. Med Univ Sofia, Dept Psychiat, Sofia 1431, Bulgaria. RP Sklar, P (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RI turton, miranda/F-4682-2011; Schaffner, Stephen/D-1189-2011; OI O'Donovan, Michael/0000-0001-7073-2379 NR 5 TC 53 Z9 55 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 2001 VL 28 IS 2 BP 126 EP 128 DI 10.1038/88836 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 437UK UT WOS:000169011800012 PM 11381257 ER PT J AU Walker, BD Korber, BT AF Walker, BD Korber, BT TI Immune control of HIV: the obstacles of HLA and viral diversity SO NATURE IMMUNOLOGY LA English DT Editorial Material ID T-LYMPHOCYTE RESPONSES; INFECTION; VIREMIA; CD8(+); IDENTIFICATION C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02114 USA. Univ Calif Los Alamos Natl Lab, Los Alamos, NM 87545 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. OI Korber, Bette/0000-0002-2026-5757 NR 27 TC 129 Z9 132 U1 1 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUN PY 2001 VL 2 IS 6 BP 473 EP 475 DI 10.1038/88656 PG 3 WC Immunology SC Immunology GA 438WV UT WOS:000169078000004 PM 11376327 ER PT J AU Lee, KH Wucherpfennig, KW Wiley, DC AF Lee, KH Wucherpfennig, KW Wiley, DC TI Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type I diabetes SO NATURE IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; GLUTAMIC-ACID DECARBOXYLASE; MYELIN BASIC-PROTEIN; T-CELL EPITOPE; HLA-DQ; PEPTIDE-BINDING; CELIAC-DISEASE; CRYSTAL-STRUCTURE; NOD MOUSE; SELF-PEPTIDES AB The class II major histocompatibility complex (MHC) glycoproteins HLA-DQ8 and HLA-DQ2 in humans and I-A(g7) in nonobese diabetic (NOD) mice are the major risk factors for increased susceptibility to type I diabetes. using X-ray crystallography, we have determined the three-dimen-sional structure of DQ8 complexed with an immunodominant peptide from insulin. The similarity of the DQ8, DQ2 and I-A(g7) peptide-binding pockets suggests that diabetes is caused by the same antigen-presentation event(s) in humans and NOD mice. Correlating type I diabetes epidemiology and MHC sequences with the DQ8 structure suggests that other structural features of the P9 pocket in addition to position 57 contribute to susceptibility to type I diabetes. C1 Childrens Hosp, Dept Med, Mol Med Lab, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Wiley, DC (reprint author), Childrens Hosp, Dept Med, Mol Med Lab, 320 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [P01 AI039619, P01 AI39619] NR 73 TC 248 Z9 254 U1 0 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUN PY 2001 VL 2 IS 6 BP 501 EP 507 DI 10.1038/88694 PG 7 WC Immunology SC Immunology GA 438WV UT WOS:000169078000012 PM 11376336 ER PT J AU Bremer, C Tung, CH Weissleder, R AF Bremer, C Tung, CH Weissleder, R TI In vivo molecular target assessment of matrix metalloproteinase inhibition SO NATURE MEDICINE LA English DT Article ID IV COLLAGENASE; TISSUE INHIBITORS; CATHEPSIN-B; CANCER; EXPRESSION; METASTASIS; GELATINASE; BLOOD; CELLS; SPECIFICITY AB A number of different matrix metalloproteinase (MMP) inhibitors have been developed as cytostatic and anti-angiogenic agents and are currently in clinical testing. One major hurdle in assessing the efficacy of such drugs has been the inability to sense or image anti-proteinase activity directly and non-invasively in vivo. We show here that novel, biocompatible near-infrared fluorogenic MMP substrates can be used as activatable reporter probes to sense MMP activity in intact tumors in nude mice. Moreover, we show for the first time that the effect of MMP inhibition can be directly imaged using this approach within hours after initiation of treatment using the potent MMP inhibitor, prinomastat (AC3340). The developed probes, together with novel near-infrared fluorescence imaging technology will enable the detailed analysis of a number of proteinases critical for advancing the therapeutic use of clinical proteinase inhibitors. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Tung, CH (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [CA088365] NR 43 TC 485 Z9 497 U1 7 U2 75 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 2001 VL 7 IS 6 BP 743 EP 748 DI 10.1038/89126 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 438YH UT WOS:000169081500045 PM 11385514 ER PT J AU Francis, NJ Kingston, RE AF Francis, NJ Kingston, RE TI Mechanisms of transcriptional memory SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID POLYCOMB-GROUP PROTEINS; CHROMATIN REMODELING COMPLEX; DROSOPHILA BITHORAX COMPLEX; CHROMOSOME-BINDING-SITES; HOMEOTIC GENE-EXPRESSION; TRITHORAX GROUP PROTEINS; SWI-SNF COMPLEX; RESPONSE ELEMENT; TARGET GENES; IN-VIVO AB How can the same gene remember that it is 'off' in one cell lineage and 'on' in another? Studies of how homeotic genes are regulated in Drosophila melanogaster have uncovered a transcriptional maintenance system, encoded by the Polycomb and trithorax group genes, that preserves expression patterns across development. Here we try to formulate a broad framework for the types of molecular mechanism used by the Polycomb and trithorax proteins. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 119 TC 262 Z9 268 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD JUN PY 2001 VL 2 IS 6 BP 409 EP 421 DI 10.1038/35073039 PG 13 WC Cell Biology SC Cell Biology GA 440FP UT WOS:000169165500013 PM 11389465 ER PT J AU Jeon, H Meng, WY Takagi, J Eck, MJ Springer, TA Blacklow, SC AF Jeon, H Meng, WY Takagi, J Eck, MJ Springer, TA Blacklow, SC TI Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID LIPOPROTEIN RECEPTORS; CRYSTAL-STRUCTURE; ATOMIC-STRUCTURE; TERMINAL DOMAIN; PROTEIN MODELS; VLDL RECEPTOR; GENE; BINDING; REFINEMENT; DROSOPHILA AB The low-density lipoprotein receptor (LDLR) is the primary mechanism for uptake of cholesterol-carrying particles into cells. The region of the LDLR implicated in receptor recycling and lipoprotein release at low pH contains a pair of calcium-binding EGF-like modules, followed by a series of six YWTD repeats and a third EGP-like module. The crystal structure at 1.5 Angstrom resolution of a receptor fragment spanning the YWTD repeats and its two flanking EGF modules reveals that the YWTD repeats form a six-bladed Beta-propeller that packs tightly against the C-terminal EGF module, whereas the EGF module that precedes the propeller is disordered in the crystal. Numerous point mutations of the LDLR that result in the genetic disease familial hypercholesterolemia (FH) alter side chains that form conserved packing and hydrogen bonding interactions in the interior and between propeller blades. A second subset of FK mutations are located at the interface between the propeller and the C-terminal EGF module, suggesting a structural requirement for maintaining the integrity of the interdomain interface. C1 Brigham & Womens Hosp, 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. Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Blacklow, SC (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM sblacklow@rics.bwh.harvard.edu NR 39 TC 143 Z9 148 U1 1 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD JUN PY 2001 VL 8 IS 6 BP 499 EP 504 DI 10.1038/88556 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 436EV UT WOS:000168924300011 PM 11373616 ER PT J AU Chun, WJ Lesort, M Tucholski, J Faber, PW MacDonald, ME Ross, CA Johnson, GVW AF Chun, WJ Lesort, M Tucholski, J Faber, PW MacDonald, ME Ross, CA Johnson, GVW TI Tissue transglutaminase selectively modifies proteins associated with truncated mutant huntingtin in intact cells SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntington's disease; huntingtin; tissue transglutaminase; polyamination; polyglutamine; immunocytochemistry ID NEURONAL INTRANUCLEAR INCLUSIONS; DIFFERENTIATED PC12 CELLS; NEURODEGENERATIVE DISEASES; POLYGLUTAMINE TRACT; GLUTAMINE REPEATS; CROSS-LINKING; EXPANDED POLYGLUTAMINE; ALZHEIMERS-DISEASE; BRAIN; INTERACTS AB The cause of Huntington's disease (HD) is a pathological expansion of the polyglutamine domain within the N-terminal region of huntingtin. Neuronal intranuclear inclusions and cytoplasmic aggregates composed of the mutant huntingtin within certain neuronal populations are a characteristic hallmark of HD. However, how the expanded polyglutamine repeats of mutant huntingtin cause HD is not known. Because in vitro expanded polyglutamine repeats are excellent glutaminyl-donor substrates of tissue transglutaminase (tTG), it has been hypothesized that tTG may contribute to the formation of these aggregates in HD. However, an association between huntingtin and tTG or modification of huntingtin by tTG has not been demonstrated in cells. To examine the interactions between tTG and huntingtin human neuroblastoma SH-SY5Y cells were stably transfected with full-length huntingtin containing 23 (FL-Q23) (wild type) or 82 (FL-Q82) (mutant) glutamine repeats or a truncated N-terminal huntingtin construct containing 23 (Q23) (wild type) or 62 (Q62) (mutant) glutamine repeats. Aggregates were rarely observed in the cells expressing full-length mutant huntingtin, and no specific colocalization of full-length huntingtin and tTG was observed. In contrast, in cells expressing truncated mutant huntingtin (Q62) there were numerous complexes of truncated mutant huntingtin and many of these complexes co-localized with tTG. However, the complexes were not insoluble structures. Further, truncated huntingtin coimmunoprecipitated with tTG, and this association increased when tTG was activated. Activation of tTG did not result in the modification of either truncated or full-length huntingtin, however proteins that were associated with truncated mutant huntingtin were selectively modified by tTG. This study is the first to demonstrate that tTG specifically interacts with a truncated form of huntingtin, and that activated tTG selectively modifies mutant huntingtin-associated proteins. These data suggest that proteolysis of full-length mutant huntingtin likely precedes its interaction with tTG and this process may facilitate the modification of huntingtin-associated proteins and thus contribute to the etiology of HD. (C) 2001 Academic Press. C1 Univ Alabama, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Neurosci, Baltimore, MD 21205 USA. RP Johnson, GVW (reprint author), Univ Alabama, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. RI Johnson, Gail/K-4723-2012; Ross, Christopher/H-8395-2013 OI Johnson, Gail/0000-0003-3464-0404; FU NIA NIH HHS [AG12396] NR 58 TC 27 Z9 29 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2001 VL 8 IS 3 BP 391 EP 404 DI 10.1006/nbdi.2001.0390 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 445LM UT WOS:000169459000003 PM 11442349 ER PT J AU Andreassen, OA Dedeoglu, A Ferrante, RJ Jenkins, BG Ferrante, KL Thomas, M Friedlich, A Browne, SE Schilling, G Borchelt, DR Hersch, SM Ross, CA Beal, MF AF Andreassen, OA Dedeoglu, A Ferrante, RJ Jenkins, BG Ferrante, KL Thomas, M Friedlich, A Browne, SE Schilling, G Borchelt, DR Hersch, SM Ross, CA Beal, MF TI Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntington's; transgenic; creatine; N-acetylaspartate; diabetes; NMR spectroscopy ID NMR MAGNETIZATION-TRANSFER; ENERGY-METABOLISM; NEURODEGENERATIVE DISEASES; REPEAT LENGTH; MOUSE MODEL; IN-VIVO; INTRANUCLEAR INCLUSIONS; NEURONAL DEATH; CAG REPEAT; MITOCHONDRIAL AB There is substantial evidence for bioenergetic defects in Huntington's disease (HD). Creatine administration increases brain phosphocreatine levels and it stabilizes the mitochondrial permeability transition. We examined the effects of creatine administration in a transgenic mouse model of HD produced by 82 polyglutamine repeats in a 171 amino acid N-terminal fragment of huntingtin (N171-82Q), Dietary supplementation of 2% creatine significantly improved survival, slowed the development of motor symptoms, and delayed the onset of weight loss. Creatine lessened brain atrophy and the formation of intranuclear inclusions, attenuated reductions in striatal N-acetylaspartate as assessed by NMR spectroscopy, and delayed the development of hyperglycemia. These results are similar to those observed using dietary creatine supplementation in the R6/2 transgenic mouse model of HD and provide further evidence that creatine may exert therapeutic effects in HD. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Neurochem Lab, Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. Boston Univ, Sch Med, Dept Neurol Pathol & Psychiat, Boston, MA 02118 USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Neurol & Neurosci, New York, NY USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD USA. RP Andreassen, OA (reprint author), Massachusetts Gen Hosp, Neurochem Lab, Neurol Unit, Boston, MA 02114 USA. RI Ross, Christopher/H-8395-2013 FU NCCIH NIH HHS [AT00613]; NIA NIH HHS [AG12992, AG13846]; NINDS NIH HHS [NS16375, NS35255, NS37102, NS38144, NS38180] NR 48 TC 182 Z9 187 U1 1 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN PY 2001 VL 8 IS 3 BP 479 EP 491 DI 10.1006/nbdi.2001.0406 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 445LM UT WOS:000169459000010 PM 11447996 ER PT J AU Barbieri, R Frank, LM Quirk, MC Wilson, MA Brown, EN AF Barbieri, R Frank, LM Quirk, MC Wilson, MA Brown, EN TI Diagnostic methods for statistical models of place cell spiking activity SO NEUROCOMPUTING LA English DT Article; Proceedings Paper CT 9th Annual Computational Neuroscience Meeting (CNS*00) CY JUL, 2000 CL BRUGGE, BELGIUM DE hippocampal place cells; interspike interval distribution; inhomogeneous gamma process; inhomogeneous inverse gaussian process; quantile-quantile plot; intensity-rescaling transformation ID RAT AB We analyze the stochastic structure of CA1 hippocampal place cell spiking activity with stimulus-response models based on inhomogeneous Poisson (IP), inhomogeneous gamma (IG) and inhomogeneous inverse Gaussian (IIG) interspike interval probability densities that have Markov dependence. We present a technique based on quantile-quantile (Q-Q) plots derived from the intensity-rescaling transformation, and use it along with Akaike's (AIC) and Bayesian (BIC) information critieria to assess model goodness of fit. The Q-Q plots give readily interpretable, graphical diagnostic methods of the model fits, and show that the IG and IIG models give more accurate descriptions of place cell spiking activity than the IP model. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp,Div Hlth Sci & Technol, Sch Med,MIT,Neurosci Stat Res Lab, Dept Anesthesia & Crit Care,Clin 3, Boston, MA 02114 USA. MIT, Neurosci Res Ctr, RIKEN, Ctr Learning & Memory,Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Barbieri, R (reprint author), Harvard Univ, Massachusetts Gen Hosp,Div Hlth Sci & Technol, Sch Med,MIT,Neurosci Stat Res Lab, Dept Anesthesia & Crit Care,Clin 3, 55 Fruit St, Boston, MA 02114 USA. OI Barbieri, Riccardo/0000-0001-9381-3833; Frank, Loren/0000-0002-1752-5677 NR 6 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-2312 J9 NEUROCOMPUTING JI Neurocomputing PD JUN PY 2001 VL 38 BP 1087 EP 1093 DI 10.1016/S0925-2312(01)00450-7 PG 7 WC Computer Science, Artificial Intelligence SC Computer Science GA 439QU UT WOS:000169129200144 ER PT J AU Gschossmann, JM Coutinho, SV Miller, JC Huebel, K Naliboff, B Wong, HC Walsh, JH Mayer, EA AF Gschossmann, JM Coutinho, SV Miller, JC Huebel, K Naliboff, B Wong, HC Walsh, JH Mayer, EA TI Involvement of spinal calcitonin gene-related peptide in the development of acute visceral hyperalgesia in the rat SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE CGRP; colorectal distension; h-CGRP8-37; visceral hyperalgesia ID GUINEA-PIG HEART; SUBSTANCE-P; CENTRAL SENSITIZATION; COLORECTAL DISTENSION; EXPERIMENTAL COLITIS; URINARY-BLADDER; SENSORY NEURONS; NEUROPEPTIDE-Y; FLEXOR REFLEX; DORSAL HORN AB This study aimed to characterize the role of the neuropeptide calcitonin gene-related peptide (CGRP) in the development of mechanically induced visceral hyperalgesia. Tonic colorectal distension (CRD) was performed in fasted, conscious male Sprague-Dawley rats. The visceromotor reflex associated with noxious CRD was determined as the number of contractions during each of two consecutive tonic distensions (10 min at 60 mmHg), which were separated by a series of phasic distensions (repeated 15-s distensions to 80 mmHg at 30-s intervals). The effect of the CGRP receptor antagonist h-CGRP(8-37) given intrathecally (i.t.) (0.03-3 nmol rat(-1)) or intravenously (i.v.) (20 mug kg(-1) bodyweight [bw]) on the visceromotor response was evaluated. The dose for i.v. administration was chosen based on previous results from similar studies. In addition, the effect of a CGRP monoclonal antibody (6 mg kg(-1) bw) given intravenously was evaluated. Compared to the baseline response, a significant increase in the number of abdominal contractions was observed during the second tonic distension. The i.t. application of h-CGRP(8-37) dose-dependently reduced the numbers of abdominal contractions both during the first and the second tonic distension period, with a maximum effect observed at a peptide concentration of 3 nmol. Intravenous administration of h-CGRP(8-37) or of the CGRP antiserum produced a small reduction of the visceromotor response induced by the second tonic distension and had no effect on colonic compliance. The development of mechanically induced colorectal hyperalgesia by repeated tonic distension involves the spinal release of CGRP, while peripheral release of CGRP plays only a minor role. C1 Univ Calif Los Angeles, Sch Med, Dept Med, CURE Digest Dis Res Ctr,Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Anim Models Core, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. Vet Adm Wadsworth Med Ctr, Los Angeles, CA 90073 USA. RP Mayer, EA (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, UCLA CURE Neuroenter Dis Program, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-40919, DK-41301] NR 53 TC 29 Z9 32 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JUN PY 2001 VL 13 IS 3 BP 229 EP 236 DI 10.1046/j.1365-2982.2001.00262.x PG 8 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 456VG UT WOS:000170102500007 PM 11437985 ER PT J AU Bonmassar, G Schwartz, DP Liu, AK Kwong, KK Dale, AM Belliveau, JW AF Bonmassar, G Schwartz, DP Liu, AK Kwong, KK Dale, AM Belliveau, JW TI Spatiotemporal brain imaging of visual-evoked activity using interleaved EEG and fMRI recordings SO NEUROIMAGE LA English DT Article DE fMRI; visual-evoked potentials; VEPs; source localization; inverse problem; forward problem; weighted minimum norm; bipolar montage; checkerboard; Hall effect ID TRIGGERED FUNCTIONAL MRI; SURFACE-BASED ANALYSIS; SENSORY STIMULATION; CORTICAL ACTIVITY; CORTEX; MAGNETOENCEPHALOGRAPHY; MEG; LOCALIZATION; POTENTIALS; HUMANS AB Combined analysis of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) has the potential to provide higher spatiotemporal resolution than either method alone. In some situations, in which the activity of interest cannot be reliably reproduced (e,g., epilepsy, learning, sleep states), accurate combined analysis requires simultaneous acquisition of EEG and fMRI. Simultaneous measurements ensure that the EEG and fMRI recordings reflect the exact same brain activity state. We took advantage of the spatial filtering properties of the bipolar montage to allow recording of very short (125-250 ms) visual-evoked potentials (VEPs) during fMRI, These EEG and fMRI measurements are of sufficient quality to allow source localization of the cortical generators. m addition, our source localization approach provides a combined EEG/fMRI analysis that does not require any manual selection of fMRI activations or placement of source dipoles, The source of the VEP was found to be located in the occipital cortex, Separate analysis of EEG and fMRI data demonstrated good spatial overlap of the observed activated sites. ks expected, the combined EEG/fMRI analysis provided better spatiotemporal resolution than either approach alone. The resulting spatiotemporal movie allows for the millisecond-to-millisecond display of changes in cortical activity caused by visual stimulation. These data reveal two peaks in activity corresponding to the N75 and the P100 components. This type of simultaneous acquisition and analysis allows for the accurate characterization of the location and timing of neurophysiological activity in the human brain, (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Univ Rennes 1, Lab SIM, Rennes, France. RP Bonmassar, G (reprint author), Bldg 149,13th St, Charlestown, MA 02129 USA. EM giorgio@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41 RR14075]; NINDS NIH HHS [R01 NS37462] NR 46 TC 112 Z9 113 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 BP 1035 EP 1043 DI 10.1006/nimg.2001.0754 PN 1 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 438MA UT WOS:000169056500009 PM 11352609 ER PT J AU Ahveninen, J Kahkonen, S Pennanen, S Liesivuori, J Jaaskelainen, IP AF Ahveninen, J Kahkonen, S Pennanen, S Liesivuori, J Jaaskelainen, IP TI Serotonin modulates human involuntary attention SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Helsinki, Cotnit Brain Res Unit, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, BioMag Lab, Helsinki, Finland. Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RI Jaaskelainen, Iiro/C-7392-2012; Liesivuori, Jyrki/O-2519-2013 OI Jaaskelainen, Iiro/0000-0001-6001-6950; NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S294 EP S294 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300295 ER PT J AU Becerra, L Breiter, H Gonzalez, RG Borsook, D AF Becerra, L Breiter, H Gonzalez, RG Borsook, D TI Noxious heat stimuli activate nucleus accumbens SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S381 EP S381 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300382 ER PT J AU Blackwell, ML Hoge, RD Davis, TL Rosen, BR AF Blackwell, ML Hoge, RD Davis, TL Rosen, BR TI Noise propagation in nonlinear BOLD signal models: Implications for MRI-based CMRO2 measurements SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S81 EP S81 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300082 ER PT J AU Bonmassar, G Van De Moortele, PF Purdon, P Jaaskelainen, I Ives, JR Vaughan, TJ Uguribil, K Belliveau, JW AF Bonmassar, G Van De Moortele, PF Purdon, P Jaaskelainen, I Ives, JR Vaughan, TJ Uguribil, K Belliveau, JW TI 7 tesla interleaved EEG and fMRI recordings: BOLD measurements SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02129 USA. Univ Minneapolis, CMRR, Minneapolis, MN 55455 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RI Jaaskelainen, Iiro/C-7392-2012; Van de Moortele, Pierre-Francois/H-5087-2011 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Van de Moortele, Pierre-Francois/0000-0002-6941-5947 NR 2 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S4 EP S4 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300005 ER PT J AU Burggren, A Small, G Sabb, F Bookheimer, SY AF Burggren, A Small, G Sabb, F Bookheimer, SY TI An attentional task in subjects at genetic risk for Alzheimer's disease SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Interdepartmental Neurosci PhD Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S643 EP S643 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300644 ER PT J AU Bush, G Vogt, BA Holmes, J Dale, A Greve, D Jenike, M Rosen, BR AF Bush, G Vogt, BA Holmes, J Dale, A Greve, D Jenike, M Rosen, BR TI Integrative model of dorsal anterior cingulate cortex supported by reward-based decision-making task and event-related FMRI SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Vogt, Brent/C-4038-2015 OI Vogt, Brent/0000-0003-1228-4410 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S303 EP S303 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300304 ER PT J AU Chen, YI Hui, KK Kong, J Kwong, KK Jenkins, BG AF Chen, YI Hui, KK Kong, J Kwong, KK Jenkins, BG TI Forepaw Electrical Stimulation at a classical acupuncture point modulates cerebral dopaminergic tone - a phMRI study SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S976 EP S976 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300975 ER PT J AU Clarke, RJ Parker, AJ Kensinger, EA Growdon, JH Corkin, S AF Clarke, RJ Parker, AJ Kensinger, EA Growdon, JH Corkin, S TI Neuroanatomical correlates of semantic memory impairment seen in normal aging and early Alzheimer's disease, as measured by functional MRI. SO NEUROIMAGE LA English DT Meeting Abstract C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S650 EP S650 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300651 ER PT J AU Fischer, H Tillfors, M Furmark, T Fredrikson, M AF Fischer, H Tillfors, M Furmark, T Fredrikson, M TI Pessimism and amygdala activity: A PET study SO NEUROIMAGE LA English DT Meeting Abstract C1 Uppsala Univ, Dept Psychol, Uppsala, Sweden. Massachusetts Gen Hosp, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Uppsala Univ, PET Ctr, Uppsala, Sweden. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S398 EP S398 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300399 ER PT J AU Hawley, ML Melcher, JR Halpin, CF AF Hawley, ML Melcher, JR Halpin, CF TI Representation of sound bandwidth in the human auditory system SO NEUROIMAGE LA English DT Meeting Abstract C1 MIT, HST Speech & Hearing Sci, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S890 EP S890 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300889 ER PT J AU Hoge, R Mandeville, JB Banzett, B Binks, A Rosen, B AF Hoge, R Mandeville, JB Banzett, B Binks, A Rosen, B TI BOLD sensitivity to systemic masking effects; comparison with flow-based fMRI SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S16 EP S16 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300017 ER PT J AU Jaaskelainen, IP Ahveninen, J May, P Tiitinen, H AF Jaaskelainen, IP Ahveninen, J May, P Tiitinen, H TI Repetitiveness of auditory environment is not required for mismatch SO NEUROIMAGE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Univ Helsinki, Cognit Brain Res Unit, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, BioMag Lab, Helsinki, Finland. Univ Helsinki, Dept Psychol, Appercept & Cort Dynam Res Team, Helsinki, Finland. RI Jaaskelainen, Iiro/C-7392-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950 NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S687 EP S687 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300687 ER PT J AU Jaaskelainen, IP Bonmassar, G Melchers, J Stufflebeam, S Hawley, M May, P Wald, L Tiitinen, H Belliveau, JW AF Jaaskelainen, IP Bonmassar, G Melchers, J Stufflebeam, S Hawley, M May, P Wald, L Tiitinen, H Belliveau, JW TI Cortical mechanisms of pre-attentive auditory "Gating" SO NEUROIMAGE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, MGH, NMR Ctr, Charlestown, MA USA. Univ Helsinki, Dept Psychol, SF-00100 Helsinki, Finland. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RI Jaaskelainen, Iiro/C-7392-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S321 EP S321 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300322 ER PT J AU Jenkins, BG Chen, IYI Brownell, AL Mandeville, JB Isacson, O AF Jenkins, BG Chen, IYI Brownell, AL Mandeville, JB Isacson, O TI Mapping dopamine receptors in the rodent and primate brain with IRON MRI: Comparisons with dopamine receptor sub-type distributions. SO NEUROIMAGE LA English DT Meeting Abstract C1 MGH NMR Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S985 EP S985 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300984 ER PT J AU Kahkonen, S Ahveninen, J Pennanen, S Liesivuori, J Jaaskelainen, I AF Kahkonen, S Ahveninen, J Pennanen, S Liesivuori, J Jaaskelainen, I TI Serotonin modulates early cortical processing in healthy subjects. Evidence from MEG study with tryptophan depletion SO NEUROIMAGE LA English DT Meeting Abstract ID MALES; MOOD C1 Univ Helsinki, Cent Hosp, BioMag Lab, Helsinki, Finland. Univ Helsinki, Cognit Brain Res Unit, Helsinki, Finland. Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland. Harvard Univ, Sch Med, NMR Ctr, Massachusetts Gen Hosp, Charlestown, MA USA. RI Jaaskelainen, Iiro/C-7392-2012; Liesivuori, Jyrki/O-2519-2013 OI Jaaskelainen, Iiro/0000-0001-6001-6950; NR 4 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1063 EP S1063 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301062 ER PT J AU Kraft, E Flaherty, AW Chen, A Kwong, KK Jenkins, BG AF Kraft, E Flaherty, AW Chen, A Kwong, KK Jenkins, BG TI Laterality and temporal influences on brain activation during sequential finger movement SO NEUROIMAGE LA English DT Meeting Abstract C1 Univ Ulm, Ulm, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1205 EP S1205 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301204 ER PT J AU Ledden, P Wald, L Hadjikhani, N Dale, A AF Ledden, P Wald, L Hadjikhani, N Dale, A TI High sensitivity RF coil system for visual fMRI studies at 3T SO NEUROIMAGE LA English DT Meeting Abstract C1 Nova Med Inc, Wakefield, MA USA. Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA USA. RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 NR 2 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S25 EP S25 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300026 ER PT J AU Lin, FH McIntosh, AR Agnew, J Zeffiro, TA Belliveau, JW AF Lin, FH McIntosh, AR Agnew, J Zeffiro, TA Belliveau, JW TI Multiple subject effective connectivity analysis of voluntary movement SO NEUROIMAGE LA English DT Meeting Abstract ID VISUAL PATHWAYS C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Boston, MA 02114 USA. Univ Toronto, Rotman Res Inst, Baycrest Ctr, Toronto, ON, Canada. Georgetown Univ, Ctr Study Learning, Gottingen, Germany. RI McIntosh, Anthony/G-4955-2011; Lin, Fa-Hsuan/G-6988-2012 OI Lin, Fa-Hsuan/0000-0002-9539-1731 NR 4 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1211 EP S1211 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301210 ER PT J AU Lin, FH Ahlfors, SP Witzel, T Dale, AM Fischl, BR Liu, AK Belliveau, JW Halgren, E AF Lin, FH Ahlfors, SP Witzel, T Dale, AM Fischl, BR Liu, AK Belliveau, JW Halgren, E TI Cancellation of MEG and EEG signals with distributed source activation on realistic cortical surface SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Boston, MA 02114 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10461 USA. RI Lin, Fa-Hsuan/G-6988-2012; Witzel, Thomas/P-1402-2014; Ahlfors, Seppo/P-3644-2016 OI Lin, Fa-Hsuan/0000-0002-9539-1731; NR 3 TC 1 Z9 1 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S186 EP S186 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300187 ER PT J AU Makris, N Jenkins, BG Vonsattel, JP Sorensen, AG Papadimitriou, GM Melrose, RJ Wu, O Cudkowicz, ME Rosen, BR Caviness, VS Kennedy, DN AF Makris, N Jenkins, BG Vonsattel, JP Sorensen, AG Papadimitriou, GM Melrose, RJ Wu, O Cudkowicz, ME Rosen, BR Caviness, VS Kennedy, DN TI Progressive Degeneration of corticospinal tract in ALS: a DTI single case longitudinal study SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol Neuropathol & Radiol, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S812 EP S812 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300811 ER PT J AU Makris, N Sahin, NT Bates, JW Patti, MR Meyer, JW Caplan, DN Caviness, VS Kennedy, DN AF Makris, N Sahin, NT Bates, JW Patti, MR Meyer, JW Caplan, DN Caviness, VS Kennedy, DN TI MRI-based volumetric analysis of anatomical consequences of stroke SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Ctr Morphometr Anal, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S813 EP S813 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300812 ER PT J AU Manoach, DS Greve, DN Lindgren, KA Dale, AM AF Manoach, DS Greve, DN Lindgren, KA Dale, AM TI Isolating the neural basis of working memory components using fMRI SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S708 EP S708 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300708 ER PT J AU Marteinsdottir, I Furmark, T Tillfors, M Agren, H Hartvig, P Fredrikson, M Langstrom, B Fischer, H Antoni, G Hagberg, G AF Marteinsdottir, I Furmark, T Tillfors, M Agren, H Hartvig, P Fredrikson, M Langstrom, B Fischer, H Antoni, G Hagberg, G TI Presynaptic serotonin imaging in social phobia using [3-11C]-5-hydroxy-L-tryptophan and PET SO NEUROIMAGE LA English DT Meeting Abstract C1 Uppsala Univ, Dept Neurosci, Uppsala, Sweden. Uppsala Univ, Dept Psychol, Uppsala, Sweden. Huddinge Univ Hosp, Div Psychiat, Dept NEUROTEC, Karolinska Inst, Stockholm, Sweden. Uppsala Univ, PET Ctr, Uppsala, Sweden. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Psychiat Neuroimaging Res Grp, Boston, MA 02114 USA. Fdn Santa Lucia, IRCCS, Lab Funct Neuroimaging, Rome, Italy. NR 5 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1070 EP S1070 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301069 ER PT J AU Salat, DH Buckner, RL Snyder, AZ Desikan, R Morris, JC Dale, AM Fischl, B AF Salat, DH Buckner, RL Snyder, AZ Desikan, R Morris, JC Dale, AM Fischl, B TI Regional cortical thinning of the aging brain SO NEUROIMAGE LA English DT Meeting Abstract ID SURFACE-BASED ANALYSIS; COORDINATE SYSTEM; PREFRONTAL GRAY; MATTER C1 Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Washington Univ, St Louis, MO 63130 USA. RI Morris, John/A-1686-2012 NR 9 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S831 EP S831 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300830 ER PT J AU Schnyer, DM Giovanello, KS West, WC Halgren, E Verfaellie, M Celli, S AF Schnyer, DM Giovanello, KS West, WC Halgren, E Verfaellie, M Celli, S TI An fMRI examination of semantic priming in a patient with semantic dementia SO NEUROIMAGE LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02118 USA. Boston DVA Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, MGH NMR Ctr, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S737 EP S737 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300736 ER PT J AU Senkfor, A Gabrieli, J AF Senkfor, A Gabrieli, J TI Episodic action memories: Recapitulation of action events revealed by fMRI SO NEUROIMAGE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Cambridge, MA 02138 USA. Stanford Univ, Stanford, CA 94305 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S739 EP S739 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300738 ER PT J AU Sigalovsky, I Hawley, ML Harms, MP Melcher, JR AF Sigalovsky, I Hawley, ML Harms, MP Melcher, JR TI Sound level representations in the human auditory pathway investigated using fMRI SO NEUROIMAGE LA English DT Meeting Abstract C1 Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S939 EP S939 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300938 ER PT J AU Sitnikova, T West, WC Holcomb, PJ AF Sitnikova, T West, WC Holcomb, PJ TI Semantic processing of pictures of animals and tools: Electrophysiological evidence on the organization of knowledge in the human brain SO NEUROIMAGE LA English DT Meeting Abstract C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuropsychol Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S604 EP S604 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300605 ER PT J AU Sperling, R Greve, D Dale, A Killiany, R Rosen, B Holmes, J Rosas, HD Cocchiarella, A Firth, P Lange, N Routledge, C Albert, M AF Sperling, R Greve, D Dale, A Killiany, R Rosen, B Holmes, J Rosas, HD Cocchiarella, A Firth, P Lange, N Routledge, C Albert, M TI Effects of lorazepam and scopolamine on encoding face-name associations: A pharmacologic fMRI trial SO NEUROIMAGE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S743 EP S743 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300742 ER PT J AU Strangman, G Bonmassar, G West, WC Hadjikhani, N Belliveau, JW Boas, DA AF Strangman, G Bonmassar, G West, WC Hadjikhani, N Belliveau, JW Boas, DA TI Simultaneous NIRS and EEG recording duffing visual stimulation SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. RI Hadjikhani, Nouchine/C-2018-2008 OI Hadjikhani, Nouchine/0000-0003-4075-3106 NR 4 TC 1 Z9 1 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S46 EP S46 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300047 ER PT J AU van der Kouwe, A Dale, A AF van der Kouwe, A Dale, A TI Real-time motion correction using octant navigators SO NEUROIMAGE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Cambridge, MA 02138 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S48 EP S48 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300049 ER PT J AU Weiss, AP Rauch, SL Alpert, NM Schacter, DL Heckers, S AF Weiss, AP Rauch, SL Alpert, NM Schacter, DL Heckers, S TI Effect of stimulus repetition and encoding strategy on subsequent episodic memory retrieval SO NEUROIMAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S759 EP S759 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300758 ER PT J AU West, WC Sitnikova, T Holcomb, PJ Caplan, D Dale, AM AF West, WC Sitnikova, T Holcomb, PJ Caplan, D Dale, AM TI Semantic processing of pictures of animals and tools: Event-related fMRI evidence on the organization of knowledge in the human brain SO NEUROIMAGE LA English DT Meeting Abstract ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; COORDINATE SYSTEM C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuropsychol Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Cambridge, MA 02138 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. NR 6 TC 1 Z9 1 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S760 EP S760 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300759 ER PT J AU Witzel, T Halgren, E Fischl, BR Liu, AK Ahlfors, SP Dale, AM AF Witzel, T Halgren, E Fischl, BR Liu, AK Ahlfors, SP Dale, AM TI Spatiotemporal imaging of brain activation using FreeSurfer SO NEUROIMAGE LA English DT Meeting Abstract ID SURFACE-BASED ANALYSIS C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. RI Witzel, Thomas/P-1402-2014; Ahlfors, Seppo/P-3644-2016 NR 6 TC 1 Z9 1 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S286 EP S286 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300287 ER PT J AU Cherny, RA Atwood, CS Xilinas, ME Gray, DN Jones, WD McLean, CA Barnham, KJ Volitakis, I Fraser, FW Kim, YS Huang, XD Goldstein, LE Moir, RD Lim, JT Beyreuther, K Zheng, H Tanzi, RE Masters, CL Bush, AI AF Cherny, RA Atwood, CS Xilinas, ME Gray, DN Jones, WD McLean, CA Barnham, KJ Volitakis, I Fraser, FW Kim, YS Huang, XD Goldstein, LE Moir, RD Lim, JT Beyreuther, K Zheng, H Tanzi, RE Masters, CL Bush, AI TI Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice SO NEURON LA English DT Article ID A-BETA; MOUSE MODEL; FREE-RADICALS; PEPTIDE; PLAQUES; PROTEIN; AGGREGATION; CLIOQUINOL; PATHOLOGY; BRAINS AB Inhibition of neocortical beta -amyloid (A beta) accumulation may be essential in an effective therapeutic intervention for Alzheimer's disease (AD). Cu and Zn are enriched in A beta deposits in AD, which are solubilized by Cu/Zn-selective chelators in vitro. Here we report a 49% decrease in brain A beta deposition (-375 mug/g wet weight, p = 0.0001) in a blinded study of APP2576 transgenic mice treated orally for 9 weeks with clioquinol, an antibiotic and bioavailable Cu/Zn chelator. This was accompanied by a modest increase in soluble A beta (1.45% of total cerebral A beta); APP, synaptophysin, and GFAP levels were unaffected. General health and body weight parameters were significantly more stable in the treated animals. These results support targeting the interactions of Cu and Zn with A beta as a novel therapy for the prevention and treatment of AD. C1 Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat Biol Genet, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Aging Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Univ Gothenburg, Sahlgrenska Univ Sjukhuset, Psychiat Sect, Inst Clin Neurosci, Molndal, Sweden. Biomol Res Inst, Parkville, Vic 3052, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Genet, Charlestown, MA 02129 USA. Univ Heidelberg, ZMBH, D-69120 Heidelberg, Germany. Baylor Coll Med, Huffington Ctr Aging, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Bush, AI (reprint author), Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RI Jones, Walton/A-2417-2011; Bush, Ashley/A-1186-2007 OI Jones, Walton/0000-0001-8642-627X; Bush, Ashley/0000-0001-8259-9069 NR 49 TC 879 Z9 918 U1 9 U2 116 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN PY 2001 VL 30 IS 3 BP 665 EP 676 DI 10.1016/S0896-6273(01)00317-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 446HY UT WOS:000169508900008 PM 11430801 ER PT J AU Tan, EK Nagamitsu, S Matsuura, T Khajavi, M Jankovic, J Ondo, W Ashizawa, T AF Tan, EK Nagamitsu, S Matsuura, T Khajavi, M Jankovic, J Ondo, W Ashizawa, T TI Alcohol dehydrogenase polymorphism and Parkinson's disease SO NEUROSCIENCE LETTERS LA English DT Article DE alcohol dehydrogenase; non-amyloid component of plaque; gene; polymorphism; Parkinson's disease; Huntington's disease ID ALPHA-SYNUCLEIN; CANDIDATE GENES; METAANALYSIS; TREMOR; ASSOCIATION; MUTATION AB a particular alcohol dehydrogenase (ADH) polymorphism (allele A1) in the promoter region of the gene has been recently demonstrated to be associated with increased risk of Parkinson's disease (PD). In a case control study, we examine frequencies of ADH A1 allele in 100 PD patients (i.e. 200 alleles), 100 diseased controls (i.e. 200 alleles), and 194 healthy controls (i.e. 388 alleles). In addition, we study possible association of a combined non-amyloid component of plaque (NACP-Rep 1) allele and ADH A1 allele with risk of PD. There was no statistical significance of the frequencies of BDH A1 allele between PD patients 12/200 (6%), diseased controls 13/200 (6.5%), and healthy controls 20/388 (5.2%). No strong evidence of an association was found between ADH A1 allele and PD susceptibility in our study patients, There was also no suggestion of linkage disequilibrium between NACP-Rep 1 and ADH A1 alleles. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Baylor Coll Med, Dept Neurol, VA Med Ctr, Houston, TX 77030 USA. RP Ashizawa, T (reprint author), Baylor Coll Med, Dept Neurol, VA Med Ctr, 6550 Fannin,Smith 1801, Houston, TX 77030 USA. NR 19 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUN 1 PY 2001 VL 305 IS 1 BP 70 EP 72 DI 10.1016/S0304-3940(01)01770-0 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 439LH UT WOS:000169118000018 PM 11356310 ER PT J AU Weaver, F Hynes, D Goldberg, JM Khuri, S Daley, J Henderson, W AF Weaver, F Hynes, D Goldberg, JM Khuri, S Daley, J Henderson, W TI Hysterectomy in Veterans Affairs Medical Centers SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SURGICAL CARE; RISK ADJUSTMENT; UNITED-STATES; REPRODUCTIVE AGE; QUALITY; COMPLICATIONS; WOMEN AB Objective: To examine the indications and surgical morbidity for women veterans who underwent hysterectomies in Department of Veterans Affairs Medical Centers (VAs). Methods: Data on hysterectomies performed in VAs from 1991 to 1997 were abstracted from a surgical quality improvement program. Results: Records of 1722 women who had hysterectomies in VAs over 6 years were examined. Women were predominately white (62%) and their average age was 42.5 years. Operations included abdominal (74%), vaginal (22%), and laparoscopic-assisted (4%) methods. The most common indications for surgery included uterine leiomyomas (31%), abnormal uterine bleeding (14%), and endometriosis (11%). Indications differed by race (P < .01); nonwhite women were most likely to have surgery for leiomyoma (51%), whereas white women had hysterectomies for leiomyomas (19%), abnormal bleeding (15%), endometriosis (13%), and genital prolapse (11%). The mean postoperative stay was significantly longer for abdominal hysterectomies (4.51 days) than either vaginal or laparoscopic-assisted hysterectomies (2.92 and 2.21 days, respectively; P < .001). The overall complication rate within 30 days was 9%, and the most frequent complication was urinary tract infection (3.3%). Conclusion: Women who underwent hysterectomies in VAs had low complication rates, comparable to hysterectomy complication rates in the United States generally. (Obstet Gynecol 2001;97:880-4. (C) 2001 by The American College of Obstetricians and Gynecologists.). C1 Edward Hines Vet Adm Med Ctr, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Edward Hines Vet Adm Med Ctr, Cooperat Studies Coordinating Ctr, Hines, IL 60141 USA. Edward Hines Vet Adm Med Ctr, VA Informat Resource Ctr, Hines, IL 60141 USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Evanston, IL USA. Loyola Univ Chicago, Dept Med, Maywood, IL USA. Univ Illinois, Coll Med, Chicago, IL USA. Boston VA Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Weaver, F (reprint author), Edward Hines Vet Adm Med Ctr, Midwest Ctr Hlth Serv & Policy Res, POB 5000 151H, Hines, IL 60141 USA. NR 23 TC 21 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2001 VL 97 IS 6 BP 880 EP 884 DI 10.1016/S0029-7844(01)01350-3 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 440ZJ UT WOS:000169206300003 PM 11384689 ER PT J AU Chen, TC Ang, RT Grosskreutz, CL Pasquale, LR Fan, JT AF Chen, TC Ang, RT Grosskreutz, CL Pasquale, LR Fan, JT TI Brimonidine 0.2% versus apraclonidine 0.5% for prevention of intraocular pressure elevations after anterior segment laser surgery SO OPHTHALMOLOGY LA English DT Article ID POSTERIOR CAPSULOTOMY; NEODYMIUM-YAG; ARGON; TRABECULOPLASTY; RISE; IRIDOTOMY; GLAUCOMA; COMPLICATIONS; 1-PERCENT; EFFICACY AB Objective: To compare the efficacy of brimonidine 0.2% with apraclonidine 0.5% in preventing intraocular pressure (IOP) elevations after anterior segment laser surgery. Design: Double-masked, randomized clinical trial. Participants: Sixty-six patients underwent either laser peripheral iridotomy, argon laser trabeculoplasty, or neodymium:yttrium-aluminum-garnet laser capsulotomy. Intervention: Eyes received either one drop of brimonidine 0.2% or apraclonidine 0.5% before laser surgery. Main Outcome Measures: Intraocular pressure, heart rate, and blood pressure were measured before laser surgery and at 1 hour, 3 hours, 24 hours, and 1 week after laser surgery. Results: Before the laser treatment, 33 patients (50.0%) received brimonidine 0.2% and 33 patients (50.0%) received apraclonidine 0.5%. Eight of 33 patients (24.2%) in the brimonidine-treated group and 9 of 33 patients (27.3%) in the apraclonidine group had postoperative IOP increases of 5 mmHg or more. This was not statistically different (P = 0.80). By the time of last follow-up examination, 3 of 33 patients (9.1%) in the brimonidine-treated group and 3 of 33 patients (9.1%) in the apraclonidine group had IOP increases of 10 mmHg or more. This was also not statistically different (P greater than or equal to 0.95). The mean IOP reduction from baseline in the brimonidine group (-2.8 +/- 2.8 mmHg) was not statistically different (P = 0.55) compared with the mean IOP reduction in the apraclonidine group (-3.6 +/- 3.3 mmHg). There were no statistically significant changes in mean heart rate or blood pressure in either group except for a slight reduction in diastolic blood pressure at 1 hour(P = 0.005) in the brimonidine group (-5.2 +/- 7.4 mmHg) compared with the apraclonidine group (-0.2 +/- 6.4 mmHg). There were no clinically significant side effects noted in either group. Conclusions: A single preoperative drop of brimonidine 0.2% is as effective as apraclonidine 0.5% in preventing IOP elevation immediately after anterior segment laser surgery. Ophthalmology 2001;108:1033-1038 (C) 2001 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv,Dept Ophthalmol, Boston, MA 02114 USA. Permanente Med Grp, Anaheim, CA USA. RP Chen, TC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 36 TC 18 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 2001 VL 108 IS 6 BP 1033 EP 1038 DI 10.1016/S0161-6420(01)00545-0 PG 6 WC Ophthalmology SC Ophthalmology GA 437YN UT WOS:000169027100028 PM 11382625 ER PT J AU Samson, CM Waheed, N Baltatzis, S Foster, CS AF Samson, CM Waheed, N Baltatzis, S Foster, CS TI Methotrexate therapy for chronic noninfectious uveitis - Analysis of a case series of 160 patients SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 24-27, 1999 CL ORLANDO, FLORIDA SP Amer Acad Ophthalmol ID LOW-DOSE METHOTREXATE; JUVENILE RHEUMATOID-ARTHRITIS; INFLAMMATORY DISEASE; PULSE METHOTREXATE; EFFICACY; MECHANISM; INTERLEUKIN-1; SAFETY; CELLS; TRIAL AB Purpose: To evaluate the outcomes of patients with chronic noninfectious uveitis unresponsive to conventional antiinflammatory therapy who were treated with methotrexate. Design: Retrospective noncomparative interventional case series. Participants: All patients with chronic noninfectious uveitis treated with methotrexate at a single institution from 1985 to 1999, Methods: Charts of patients seen on the Ocular Immunology & Uveitis Service at the Massachusetts Eye & Ear Infirmary were reviewed. Patients with chronic uveitis of noninfectious origin treated with methotrexate were included in the study. Main Outcome Measures: Control of inflammation, steroid-sparing effect, visual acuity, adverse reactions. Results: A total of 160 patients met the inclusion criteria, Control of inflammation was achieved in 76.2% of patients. Steroid-sparing effect was achieved in 56% of patients, Visual acuity was maintained or improved in 90% of patients. Side effects requiring discontinuation of medication occurred in 18% of patients, Potentially serious adverse reactions occurred in only 8.1% of patients. There was neither long-term morbidity nor mortality caused by methotrexate. Conclusions: Methotrexate is effective in the treatment of chronic noninfectious uveitis that fails to respond to conventional steroid treatment. It is an effective steroid-sparing immunomodulator, is a safe medication, and is well tolerated. Ophthalmology 2001;108:1134-1139 (C) 2001 by the American Academy of Ophthalmology. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ocular Immunol & Uveitis Serv, Boston, MA 02116 USA. Univ Athens, Dept Ophthalmol, Athens, Greece. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02116 USA. NR 31 TC 128 Z9 132 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 2001 VL 108 IS 6 BP 1134 EP 1139 DI 10.1016/S0161-6420(01)00576-0 PG 6 WC Ophthalmology SC Ophthalmology GA 437YN UT WOS:000169027100045 PM 11382642 ER PT J AU Zhao, HZ Liang, R Li, DC Cao, M AF Zhao, HZ Liang, R Li, DC Cao, M TI Practical common-path heterodyne surface profiling interferometer with automatic focusing SO OPTICS AND LASER TECHNOLOGY LA English DT Article DE common-path heterodyne interferometer; automatic focusing; phase measurement ID ROUGHNESS; PROFILOMETRY AB In modern semiconductor and optics industries, there is a strong demand for a highly sensitive and non-contact surface profilometer. This paper describes a practical heterodyne surface profiling interferometer for on-line non-contact measurement which has been developed recently. The essential feature of the profilometer is a newly designed common-path configuration to minimize the effects caused by vibration, air turbulence and other environmental variations. A single-mode frequency-stabilized laser diode (780 nm) serves as the light source to make the whole system compact (total volume 250L x 200W x 100H mm). A powerful signal processing scheme is also developed, which includes three parts: automatic voltage control, phase measurement with wide range and automatic focusing control. All these make the repeatability and stability of the profiling interferometer greatly improved. The system has vertical resolution of 0.39 nm and lateral resolution of 0.73 mum. During approximately an hour, the stability is within 1.95 nm(3 sigma). (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Tsing Hua Univ, Dept Precis Instruments, Beijing 100084, Peoples R China. RP Zhao, HZ (reprint author), Massachusetts Gen Hosp, Wellman Lab, BAR 713,40 Blossom St, Boston, MA 02114 USA. NR 14 TC 11 Z9 12 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0030-3992 J9 OPT LASER TECHNOL JI Opt. Laser Technol. PD JUN PY 2001 VL 33 IS 4 BP 259 EP 265 DI 10.1016/S0030-3992(01)00035-4 PG 7 WC Optics; Physics, Applied SC Optics; Physics GA 444WW UT WOS:000169423900011 ER PT J AU Redding, SW Bailey, CW Lopez-Ribot, JL Kirkpatrick, WR Fothergill, AW Rinaldi, MG Patterson, TF AF Redding, SW Bailey, CW Lopez-Ribot, JL Kirkpatrick, WR Fothergill, AW Rinaldi, MG Patterson, TF TI Candida dubliniensis in radiation-induced oropharyngeal candidiasis SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article; Proceedings Paper CT 78th General Session of the International-Association-for-Dental-Research CY MAR-APR -, 2000 CL WASHINGTON, D.C. SP Int Assoc Dent Res ID ELECTROPHORETIC KARYOTYPE; ORAL CANDIDIASIS; ALBICANS; SUSCEPTIBILITY; FLUCONAZOLE; AIDS; COLONIZATION AB Candida dubliniensis is a recently described species that has been shown to cause oropharyngeal candidiasis in patients with HIV. We present a detailed evaluation of a patient undergoing head and neck radiation for oral cancer who developed oropharyngeal candidiasis from a mixed infection of C dubliniensis and Candida albicans. To our knowledge, this is the first described case of C dubliniensis contributing to oropharyngeal candidiasis in this patient population. C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Gen Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Pathol, San Antonio, TX 78229 USA. RP Redding, SW (reprint author), Univ Texas, Hlth Sci Ctr, S Texas Vet Healthcare Syst, Dept Gen Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. RI Lopez-Ribot, Jose/D-2048-2010 FU NIDCR NIH HHS [R01DE11381] NR 12 TC 11 Z9 13 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUN PY 2001 VL 91 IS 6 BP 659 EP 662 DI 10.1067/moe.2001.112946 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 445LB UT WOS:000169458000010 PM 11402278 ER PT J AU Wang, SJ Mintz, LE Natarajan, V Lee, NJ Srivatsan, ES Wang, MB AF Wang, SJ Mintz, LE Natarajan, V Lee, NJ Srivatsan, ES Wang, MB TI Third Place-Resident Research Competition, AAO-2000 - Antisense cyclin D1 inhibits growth of head and neck cancer xenografts in nude mice SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 24-29, 2000 CL WASHINGTON, D.C. SP Amer Acad Otolaryngol Head & Neck Surg ID SQUAMOUS-CELL CARCINOMA; CHROMOSOME 11Q13 AMPLIFICATION; HUMAN ESOPHAGEAL CANCER; POOR-PROGNOSIS; GENE; PHOSPHORYLATION; TUMORIGENICITY; PROLIFERATION; ASSOCIATION; EXPRESSION AB PROBLEM: Cyclin DI is a regulatory factor essential in the progression of the cell cycle from G1 through S phase. Amplification and overexpression of cyclin DI have been observed in many human cancers including head and neck squamous cell carcinoma (HNSCC). We have previously transfected a HNSCC control cell line (CCL23) with an antisense cyclin DI plasmid and demonstrated inhibition of cell proliferation in vitro. In this study, we examine whether antisense cyclin DT could inhibit tumor growth in vivo. METHODS/MEASURES: The CCL23 and its antisense cyclin D1 transfected clone (CCL23 AS) were injected into the flanks of nude mice. Tumor growth was monitored weekly, After 5 weeks, tumors were removed and studied for tumor size, cyclin D1 expression, cyclin D1-dependent kinase activity, and retinoblastoma (Rb) phosphorylation. RESULTS: Compared with the control tumors, 11 of 19 antisense tumors were smaller, 7 tumors were of equal size, and I tumor was larger. Immunohistochemical analysis with an anti-cyclin D1 antibody demonstrated decreased cyclin D1 expression in CCL23 AS and the smaller antisense tumors. Cyclin D1-dependent kinase activity was reduced in CCL23 AS and the smaller anti-sense tumors, and this was accompanied by a relative decrease in phosphorylated Rb in these samples. CONCLUSION: Antisense cyclin D1 inhibits growth of HNSCC tumors. Cyclin D1 expression, cyclin D1-dependent kinase activity, and Rb phosphorylation: are decreased in these tumors. CLINICAL SIGNIFICANCE: These findings lend support for the potential use of antisense cyclin D1 as gene therapy for HNSCC. C1 Univ Calif Los Angeles, Med Ctr, Div Head & Neck Surg, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90024 USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, Med Ctr, Div Head & Neck Surg, Sch Med, CHS 62-132,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 21 TC 6 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 2001 VL 124 IS 6 BP 656 EP 662 DI 10.1067/mhn.2001.116039 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 442CX UT WOS:000169268600010 PM 11391257 ER PT J AU Casarett, DJ Karlawish, J AF Casarett, DJ Karlawish, J TI Beyond informed consent: The ethical design of pain research SO PAIN MEDICINE LA English DT Article DE pain; ethics; research ethics; informed consent ID CONTROLLED-RELEASE OXYCODONE; QUALITY-OF-LIFE; CANCER-PATIENTS; CLINICAL RESEARCH; ORAL MORPHINE; DOUBLE-BLIND; TRANSDERMAL FENTANYL; SATISFACTION; TRIALS; MANAGEMENT AB In the wake of the rapid development of medical research over the past 50 years, investigators, clinicians, and ethicists have raised numerous concerns about the ethical conduct of research. Perhaps the single most important protective mechanism to emerge from the fray has been flue requirement of informed consent. Certainly it has the longest history. however, even th ugh informed consent has become the most widely recognized mechanism of protecting human subjects in research, there are limits to what the informed consent process can accomplish. Another, anti more tar-reaching, way to protect human subjects involved in research is to ensure that the study design is as consistent as possible with patients' preferences and goals. That is, pain investigators have a significant opportunity to improve the ethical rigor of their work by designing a study that offers a subject what is a reasonable balance of risks and benefits. This article suggests some specific: ways in which investigators may design research that is more consistent with patient preferences. We describe several aspects of the ethical design of clinical pain research that appear to be important to patients, including the potential benefits for subjects, the benefits for future patients, the risks anti burdens of research participation, and the voluntariness of a subject's choice whether to enroll. We conclude fy discussing ways in which the ethical design of research might make the informed consent process more robust. C1 Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Inst Aging, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. RP Casarett, DJ (reprint author), Univ Penn, Philadelphia VA Med Ctr, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 61 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD JUN PY 2001 VL 2 IS 2 BP 138 EP 146 DI 10.1046/j.1526-4637.2001.002002138.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 458YQ UT WOS:000170223400010 PM 15102303 ER PT J AU Albers, S Marsden, D Quackenbush, E Stark, AR Levy, HL Irons, M AF Albers, S Marsden, D Quackenbush, E Stark, AR Levy, HL Irons, M TI Detection of neonatal carnitine palmitoyltransferase II deficiency by expanded newborn screening with tandem mass spectrometry SO PEDIATRICS LA English DT Article DE fatty acid oxidation; dysmorphic; calcification; neonatal death ID DYSGENESIS; MUSCLE AB The introduction of tandem mass spectrometry to newborn screening has substantially expanded our ability to diagnose metabolic diseases in the newborn period. We report the first case of neonatal carnitine palmitoyltransferase deficiency II detected by expanded newborn screening with tandem mass spectrometry. The neonate presented with dysmorphic facial features, structural malformations, renal failure, seizures, and cardiac arrythmias and died on the third day of life. This experience illustrates the importance of expanded newborn screening to avoid missing a metabolic diagnosis in early infantile death. C1 Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Boston, MA 02125 USA. New England Newborn Screening Program, Boston, MA USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Albers, S (reprint author), Childrens Hosp, Div Genet, 300 Longwood Ave, Boston, MA 02115 USA. FU NHGRI NIH HHS [R0I HG02085]; PHS HHS [5H 46 MC 00158-02] NR 18 TC 13 Z9 13 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2001 VL 107 IS 6 BP art. no. EP e103 DI 10.1542/peds.107.6.e103 PG 4 WC Pediatrics SC Pediatrics GA 439HJ UT WOS:000169105500018 PM 11389301 ER PT J AU Germano, PM Stalter, J Le, SV Wu, M Yamaguchi, DJ Scott, D Pisegna, JR AF Germano, PM Stalter, J Le, SV Wu, M Yamaguchi, DJ Scott, D Pisegna, JR TI Characterization of the pharmacology, signal transduction and internalization of the fluorescent PACAP ligand, fluor-PACAP, on NIH/3T3 cells expressing PAC1 SO PEPTIDES LA English DT Article DE PACAP; confocal microscopy; fluo-PACAP; PAC1; NIH; 3T3 cells; pharmacology ID CYCLASE-ACTIVATING POLYPEPTIDE; ADENYLATE-CYCLASE; I RECEPTOR; RAT-BRAIN; PITUITARY; PEPTIDE; LOCALIZATION; CLONING; TISSUE AB Fluor-PACAP, a fluorescent derivative of PACAP-27, has been confirmed to share a high affinity for PACl receptors transfected into NIH/3T3 cells and to have comparable pharmacological characteristics to the unconjugated, native form. Through competitive binding with I-125-PACAP-27, the two ligands exhibited similar dose- dependent inhibition. Additional examination of the efficacy of activating adenylyl cyclase revealed that both ligands analogously stimulated the production of cyclic AMP. Furthermore, PACl internalization visualized by our Fluor-PACAP, is compareable to that performed with the radioligand, I-125-PACAP-27, with maximal internalization achieved within thirty minutes. Thus, Fluor-PACAP exhibits intracellular signaling abilities homologous to the native ligand. (C) 2001 Elsevier Science Inc. All rights reserved. C1 VA Greater Los Angeles Hlth Care Syst, CURE VA UCLA Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Hlth Care Syst, CURE VA UCLA Digest Dis Res Ctr, Los Angeles, CA 90073 USA. NR 17 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUN PY 2001 VL 22 IS 6 BP 861 EP 866 DI 10.1016/S0196-9781(01)00410-7 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 440NT UT WOS:000169181800002 PM 11390014 ER PT J AU Orsi, A Sherman, O Woldeselassie, Z AF Orsi, A Sherman, O Woldeselassie, Z TI Simvastatin-associated memory loss SO PHARMACOTHERAPY LA English DT Article ID COA REDUCTASE INHIBITORS; PRAVASTATIN; HYPERCHOLESTEROLEMIA; LOVASTATIN AB The statins are widely used to treat dyslipidemias. They are generally associated with mild adverse effects, but rarely, more serious reactions may occur. A 51-year-old man experienced delayed-onset, progressive memory loss while receiving simvastatin for hypercholesterolemia. His therapy was switched to pravastatin, and memory loss resolved gradually over the next month, with no recurrence of the adverse effect. C1 Bronx Vet Adm Med Ctr, Pharm Program, Bronx, NY 10468 USA. Bronx Vet Adm Med Ctr, Primary Care Patient Care Ctr, Bronx, NY 10468 USA. RP Sherman, O (reprint author), Bronx Vet Adm Med Ctr, Pharm Program, 119,130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 14 TC 45 Z9 49 U1 0 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUN PY 2001 VL 21 IS 6 BP 767 EP 769 DI 10.1592/phco.21.7.767.34577 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 470AX UT WOS:000170849200013 PM 11401190 ER PT J AU Pfefer, TJ Schomacker, KT Nishioka, NS AF Pfefer, TJ Schomacker, KT Nishioka, NS TI Long-term effects of photodynamic therapy on fluorescence spectroscopy in the human esophagus SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID HIGH-GRADE DYSPLASIA; BARRETTS-ESOPHAGUS; PROTOPORPHYRIN-IX; CANCER-DIAGNOSIS; AUTOFLUORESCENCE; TISSUE; PHOTOFRIN; BIOLOGY AB Clinical interest in laser-induced fluorescence (LIF) spectroscopy and photodynamic therapy (PDT) is growing rapidly and may ultimately lead to close parallel use of these techniques. However, variations in LIF due to photosensitizer retention as well as tissue damage and healing processes may interfere with autofluorescence-based diagnostic methods. We have investigated the compatibility of these two techniques by quantifying PDT-induced changes in LIF in the human esophagus. Fluorescence spectra were collected endoscopically at excitation wavelengths (lambda (ex)) of 337, 400 and 410 nm in 32 patients. Measurements were performed immediately before and after PDT treatment with porfimer sodium and during follow-up procedures. In the months following PDT regions of reepithelialized squamous showed reduced autofluorescence in comparison with untreated squamous regions (P = 0.0007). Photosensitizer fluorescence was undetectable with lambda (ex) = 337 nm during follow-up procedures, whereas for lambda (ex) = 400 and 410 nm porfimer sodium fluorescence was noted for nearly a year after treatment, Therefore, residual photosensitizer fluorescence is likely to affect certain LIF-based diagnostic techniques during a period when patients are at high risk for tumor recurrence. Modification of LIF systems and/or the use of alternative photosensitizers may be required to optimize the detection of lesions in the post-PDT patient. Given the potential of LIF as a method for surveillance following cancer therapy, further investigation of the compatibility of specific LIF approaches with cancer pharmaceuticals may be warranted. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Gastrointestinal Unit, Boston, MA USA. RP Nishioka, NS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Bartlett 708,55 Fruit St, Boston, MA 02114 USA. RI Pfefer, Josh/I-9055-2012 NR 27 TC 6 Z9 6 U1 0 U2 4 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 2001 VL 73 IS 6 BP 664 EP 668 DI 10.1562/0031-8655(2001)073<0664:LTEOPT>2.0.CO;2 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 441TY UT WOS:000169246700013 PM 11421073 ER PT J AU Barton, JK Rollins, A Yazdanfar, S Pfefer, TJ Westphal, V Izatt, JA AF Barton, JK Rollins, A Yazdanfar, S Pfefer, TJ Westphal, V Izatt, JA TI Photothermal coagulation of blood vessels: a comparison of high-speed optical coherence tomography and numerical modelling SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PORT-WINE STAINS; LASER TREATMENT; IRRADIATION; TISSUE; PULSE; NM AB Optical-thermal models that can accurately predict temperature rise and damage in blood vessels and surrounding tissue may be used to improve the treatment of vascular disorders. Verification of these models has been hampered by the lack of time- and depth-resolved experimental data. In this preliminary study, an optical coherence tomography system operating at 4-30 frames per second was used to visualize laser irradiation of cutaneous (hamster dorsal skin flap) blood vessels. An argon laser was utilized with the following parameters: pulse duration 0.1-2.0 s, spot size 0.1-1.0 mm, power 100-400 mW. Video microscopy images were obtained before and after irradiations, and optical-thermal modelling was performed on two irradiation cases. Time-resolved optical coherence tomography and still images were compared with predictions of temperature rise and damage using Monte Carlo and finite difference techniques. In general, predicted damage agreed with the actual blood vessel and surrounding tissue coagulation seen in images. However, limitations of current optical-thermal models were identified. such as the inability to model the dynamic changes in blood vessel diameter that were seen in the optical coherence tomography images. C1 Univ Arizona, Div Biomed Engn, Tucson, AZ 85721 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Barton, JK (reprint author), Univ Arizona, Div Biomed Engn, 1230 E Speedway Blvd, Tucson, AZ 85721 USA. RI Yazdanfar, Siavash/A-9013-2009; Tewatia, Dinesh/D-5897-2012; Pfefer, Josh/I-9055-2012 OI Yazdanfar, Siavash/0000-0003-2768-6199; NR 26 TC 28 Z9 31 U1 0 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JUN PY 2001 VL 46 IS 6 BP 1665 EP 1678 DI 10.1088/0031-9155/46/6/306 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 441XD UT WOS:000169254100006 PM 11419626 ER PT J AU Jander, G Cui, JP Nhan, B Pierce, NE Ausubel, FM AF Jander, G Cui, JP Nhan, B Pierce, NE Ausubel, FM TI The TASTY locus on chromosome 1 of Arabidopsis affects feeding of the insect herbivore Trichoplusia ni SO PLANT PHYSIOLOGY LA English DT Article ID QUANTITATIVE GENETIC-VARIATION; RECOMBINANT INBRED LINES; CABBAGE-LOOPER; TRAIT LOCI; THALIANA; RESISTANCE; DEFENSE; LEPIDOPTERA; POPULATIONS; DETERRENCY AB The generalist insect herbivore Trichoplusia ni (cabbage looper) readily consumes Arabidopsis and can complete its entire life cycle on this plant. Natural isolates (ecotypes) of Arabidopsis are not equally susceptible to T. ni feeding. While some are hardly touched by T. ni, others are eaten completely to the ground. Comparison of two commonly studied Arabidopsis ecotypes in choice experiments showed that Columbia is considerably more resistant than Landsberg erecta. In no-choice experiments, where larvae were confined on one or the other ecotype, weight gain was more rapid on Landsberg erects than on Columbia. Genetic mapping of this difference in insect susceptibility using recombinant inbred lines resulted in the discovery of the TASTY locus near 85 cM on chromosome 1 of Arabidopsis. The resistant allele of this locus is in the Columbia ecotype, and an F, hybrid has a sensitive phenotype that is similar to that of Landsberg erecta. The TASTY locus is distinct from known genetic differences between Columbia and Landsberg erecta that affect glucosinolate content, trichome density, disease resistance, and flowering time. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. EM ausubel@frodo.mgh.harvard.edu FU NIGMS NIH HHS [F32 GM018735, R01 GM048707, GM18735, R37 GM048707, GM48707] NR 47 TC 62 Z9 63 U1 3 U2 11 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 EI 1532-2548 J9 PLANT PHYSIOL JI Plant Physiol. PD JUN PY 2001 VL 126 IS 2 BP 890 EP 898 DI 10.1104/pp.126.2.890 PG 9 WC Plant Sciences SC Plant Sciences GA 442QT UT WOS:000169297000044 PM 11402216 ER PT J AU Abrahm, JL Snyder, L AF Abrahm, JL Snyder, L TI Pain assessment and management SO PRIMARY CARE LA English DT Review ID TRANSMUCOSAL FENTANYL CITRATE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CONTROLLED-RELEASE MORPHINE; COOPERATIVE-ONCOLOGY-GROUP; CONTROLLED CLINICAL-TRIAL; SPINAL-CORD COMPRESSION; CANCER PAIN; BREAKTHROUGH PAIN; BONE METASTASES; NURSING-HOME AB Assessment and management of pain is crucial to the success of any program of care for dying patients and their families. With appropriate assessment and management, often using home health or hospice teams, pain can be controlled in more than 90% of patients. This article focuses on the symptomatic care of patients who are dying. The legal and regulatory issues that may inhibit delivery of adequate opioid therapy are also reviewed. C1 Amer Coll Phys, Ctr Eth & Professionalism, Amer Soc Internal Med, Philadelphia, PA USA. Univ Penn, Ctr Bioeth, Dept Bioeth, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Palliat Care Programs, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Abrahm, JL (reprint author), Dana Farber Canc Inst, Palliat Care Programs, 44 Binney St, Boston, MA 02115 USA. NR 144 TC 3 Z9 3 U1 4 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-4543 J9 PRIMARY CARE JI Primary Care PD JUN PY 2001 VL 28 IS 2 BP 269 EP + DI 10.1016/S0095-4543(05)70022-1 PG 30 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 452JQ UT WOS:000169854900004 PM 11406435 ER PT J AU Navon, M Nelson, D Pagano, M Murphy, M AF Navon, M Nelson, D Pagano, M Murphy, M TI Use of the pediatric symptom checklist in strategies to improve preventive behavioral health care SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-HEALTH; PSYCHOSOCIAL DYSFUNCTION; FUNCTIONAL IMPAIRMENT; RISK-FACTORS; CHILDREN; COMMUNITY; PSYCHOPATHOLOGY; MALADJUSTMENT; DISORDERS; MORBIDITY AB Obiective: The purpose of this study was to examine the utility of the Pediatric Symptom Checklist (PSC) in identifying youth at risk of behavioral health problems and to develop strategies to meet their mental health needs. Methods: The PSC was completed by the parents of 570 children aged two to 18 years at three urban health centers in Massachusetts. Follow-up interviews were conducted with the parents of 95 of the children. Multidisciplinary teams held case conferences to review the cases of 43 of the 95 children who were interviewed and who were determined to have moderate to severe behavioral health problems. Results: Of the 570 children in the screening sample, 144 (25 percent) had moderate to severe behavioral health problems, as indicated by a positive score on the PSC, and 2 percent had a serious emotional disturbance. Of the 297 pre-school-aged children (younger than six years), 67 (23 percent) received a positive score. Of the 283 school-aged children (age six and older) from both English- and Spanish-speaking families, 77 (27 percent) received a positive score. About one-third of the severely emotionally disturbed youth were receiving some mental health treatment, but only 20 percent were rated by the multidisciplinary team as receiving adequate treatment. Conclusions: The study provided further support for the validity and reliability of the PSC and confirmed the results of earlier studies that found a high level of unmet needs for mental health services among this population. Use of the PSC in this study promoted an increase in referrals for children in need. C1 Neighborhood Hlth Plan, Boston, MA USA. Lightbridge Inc, Burlington, MA USA. Beacon Hlth Strategies, Woburn, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Navon, M (reprint author), 8 Jackson Rd, Marblehead, MA 01945 USA. FU NIAAA NIH HHS [L30 AA014994-01, L30 AA014994] NR 26 TC 35 Z9 36 U1 2 U2 7 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD JUN PY 2001 VL 52 IS 6 BP 800 EP 804 DI 10.1176/appi.ps.52.6.800 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 438RG UT WOS:000169066800012 PM 11376228 ER PT J AU Alterman, AI Bovasso, GB Cacciola, JS McDermott, PA AF Alterman, AI Bovasso, GB Cacciola, JS McDermott, PA TI A comparison of the predictive validity of four sets of baseline ASI summary indices SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article ID ADDICTION SEVERITY INDEX; RELIABILITY AB This study compared the long-term predictive validity of original and new baseline Addiction Severity Index summary scores in methadone patients. The indices included the original Interviewer Severity Ratings (ISRs) and the new Clinical Indices (CIs), which use both lifetime and recent problem information, and the original Composite Scores (CSs) and Evaluation Indices (EIs), based on recent problems only. Outcomes were medical hospitalization, employment, alcohol intoxication, drug hospitalization, and psychiatric hospitalization in Months 7-24 poststudy entry and criminal charges in Months 0-24. Hierarchical logistic regression analyses were used in which 1 index was entered first and the other in the 2nd step. The reverse order of entry was used in a 2nd analysis. A final analysis set compared the best predictor from each of the 2 prior analysis sets, The Cls were superior to the other indices in predicting 3 of 6 outcomes (psychiatric hospitalization, drug hospitalization, and criminal char.-es); the EI was the best predictor of alcohol intoxication, and the CS the best predictor of unemployment. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Grad Sch Educ, Philadelphia, PA 19104 USA. RP Alterman, AI (reprint author), Univ Penn, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. NR 9 TC 31 Z9 31 U1 2 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD JUN PY 2001 VL 15 IS 2 BP 159 EP 162 DI 10.1037/0893-164X.15.2.159 PG 4 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 472DD UT WOS:000170967300011 PM 11419233 ER PT J AU White, SM Held, KD Palmer, MR Yanch, JC AF White, SM Held, KD Palmer, MR Yanch, JC TI Biological dosimetry for epithermal neutron beams SO RADIATION RESEARCH LA English DT Article ID CAPTURE THERAPY; IN-VITRO AB The radiobiological effectiveness of an epithermal neutron beam is described using cell survival as the end point. The M67 epithermal neutron beam at the Nuclear Reactor Laboratory, Massachusetts Institute of Technology, that was used for clinical trials of boron neutron capture therapy was used to irradiate Chinese hamster ovary cells at seven depths in a water-filled phantom that simulated healthy tissue. No boron was added to the samples. Therefore, this experiment evaluates the biological effectiveness of the neutron and photon components, which comprise 80-95% of the dose to healthy tissue. Cell survival was dependent upon the depth in the phantom, as a result of moderation and attenuation of the epithermal neutron beam components by the overlying water. The results were compared with 250 kVp X irradiations to determine relative biological effectiveness values. Cell survival as a function of the dose delivered was lowest at the most shallow depth of 0.5 cm, and increased at depths of 1.5, 3, 4, 5.6, 6.6 and 8.1 cm. The gradual increase in cell survival with increasing depth in the phantom is due to the exponential drop of the fast-neutron intensity of the beam. These results are applicable to clinical boron neutron capture therapy Phase VII trials in which healthy tissue toxicity was an end point. (C) 2001 by Radiation Research Society. C1 MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP White, SM (reprint author), MIT, Dept Nucl Engn, NW14-2321,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM smwhite@mit.edu NR 22 TC 2 Z9 2 U1 0 U2 2 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 2001 VL 155 IS 6 BP 778 EP 784 DI 10.1667/0033-7587(2001)155[0778:BDFENB]2.0.CO;2 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 437KX UT WOS:000168991800003 PM 11352759 ER PT J AU Stone, ME AF Stone, ME TI Gay and lesbian families: A bibliography, no. 57. SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Ref Serv, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Ref Serv, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD SUM PY 2001 VL 40 IS 4 BP 386 EP 387 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 457GC UT WOS:000170127900027 ER PT J AU Craig, WA AF Craig, WA TI Re-evaluating current antibiotic therapy SO RESPIRATORY MEDICINE LA English DT Article DE bacteriological eradication; nasopharyngeal carriage; pharmacodynamics; pharmacokinetics; pneumococcal resistance; susceptibility breakpoints ID ACUTE OTITIS-MEDIA; RESISTANT STREPTOCOCCUS-PNEUMONIAE; AMOXICILLIN-CLAVULANATE; PNEUMOCOCCAL RESISTANCE; CLINICAL EFFICACY; WORKING GROUP; RISK-FACTORS; PHARMACODYNAMICS; MANAGEMENT; CARRIAGE AB Pharmacokinetic/pharmacodynamic (PK/PD) parameters derived from animal and clinical models of infection are used to predict bacteriological efficacy. Growing evidence from the clinical setting supports the validity of these parameters in guiding antimicrobial therapy. For example, in otitis media and sinusitis, high bacteriological cure rates are obtained when serum concentrations of beta -lactams and macrolides exceed the MIC of the infecting pathogen for at least 40% of the dosing interval. Likewise, the 24-hour AUC/MIC ratio is a good predictor of both bacteriological and clinical efficacy for azithromycin in otitis media and fluoroquinolones in bacterial pneumonia. The value of PK/PD relationships has been recognized by the National Committee for Clinical Laboratory Standards (NCCLS) as another important factor to consider when establishing susceptibility breakpoints. Recent changes to NCCLS breakpoints for oral beta -lactams for Streptococcus pneumoniae reflect this. Also, PK/PD parameters may play a role in predicting the impact of an antibiotic on the development and spread of resistant organisms. In an era of increasing resistance, we should select agents and doses that provide drug concentrations that exceed the magnitude of the PK/PD parameter required both for efficacy and to combat the emergence and spread of bacterial resistance. C1 William S Middleton Mem Vet Adm Hosp, Madison, WI USA. RP Craig, WA (reprint author), D-2221,2500 Overlook Terrace, Madison, WI 53705 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JUN PY 2001 VL 95 SU A BP S14 EP S21 DI 10.1053/rmed.2001.1088 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 441RK UT WOS:000169243200004 ER PT J AU Craig, WA AF Craig, WA TI Bacterial respiratory infections: closing in on antibiotic effectiveness... and ineffectiveness - Introduction SO RESPIRATORY MEDICINE LA English DT Editorial Material DE antibiotic consumption; antibiotic resistance; community-acquired respiratory tract infections; prevalence ID COMMUNITY-ACQUIRED PNEUMONIA; SUSCEPTIBILITY C1 William S Middleton Mem Vet Adm Hosp, Madison, WI USA. RP Craig, WA (reprint author), D-2221,2500 Overlook Terrace, Madison, WI 53705 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD JUN PY 2001 VL 95 SU A BP S4 EP S6 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 441RK UT WOS:000169243200002 ER PT J AU DePinho, RA Jacks, T AF DePinho, RA Jacks, T TI Tumor induction in suppressor gene knockout mice - Introduction SO SEMINARS IN CANCER BIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD JUN PY 2001 VL 11 IS 3 BP 175 EP 176 DI 10.1006/scbi.2000.0369 PG 2 WC Oncology SC Oncology GA 447YW UT WOS:000169600900001 PM 11407942 ER PT J AU Bardeesy, N Sharpless, NE DePinho, RA Merlino, G AF Bardeesy, N Sharpless, NE DePinho, RA Merlino, G TI The genetics of pancreatic adenocarcinoma: a roadmap for a mouse model SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE pancreatic cancer; transgenic mouse; genetics ID TRANSFORMING-GROWTH-FACTOR; TUMOR-SUPPRESSOR GENE; PEUTZ-JEGHERS-SYNDROME; TRANSGENIC MICE; EXOCRINE PANCREAS; FACTOR-BETA; CANCER-CELLS; TGF-BETA; TELOMERASE ACTIVITY; JUVENILE POLYPOSIS AB Pancreatic cancer is among the leading causes of cancer death. Although a genetic profile for pancreatic cancer is emerging, many biological aspects of this disease are poorly understood. Indeed fundamental questions regarding progenitor cell lineages, host stromal milieu, and the role of specific genetic alterations in tumor progression remain unresolved. A mouse model engineered with signature mutations would provide a powerful ally in the study of pancreatic cancer biology and may guide improved prognostic assessment and treatment for the human disease. In this review, we discuss the molecular basis for normal pancreatic development and the genetics of human pancreatic adenocarcinoma in the hope of charting a course for the development of a faithful mouse model for this lethal cancer. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Bardeesy, N (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 151 TC 24 Z9 25 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD JUN PY 2001 VL 11 IS 3 BP 201 EP 218 DI 10.1006/scbi.2000.0371 PG 18 WC Oncology SC Oncology GA 447YW UT WOS:000169600900004 PM 11407945 ER PT J AU Chang, S Khoo, C DePinho, RA AF Chang, S Khoo, C DePinho, RA TI Modeling chromosomal instability and epithelial carcinogenesis in the telomerase-deficient mouse SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE mouse models; telomere; telomerase; carcinoma; genomic instability; p53; cancer; non-reciprocal translocations; fusion-bridge-breakage translocation ID COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN-DIPLOID FIBROBLASTS; CATALYTIC SUBUNIT GENE; LI-FRAUMENI-SYNDROME; NORMAL HUMAN-CELLS; CARCINOMA IN-SITU; LARGE T-ANTIGEN; WILD-TYPE P53; COLORECTAL-CANCER; CELLULAR SENESCENCE AB Human carcinomas are intimately linked to advancing age. These cancers have complex cytogenetic profiles, including aneuploidy and chromosomal structural aberrations. While aged humans sustain a high rate of carcinomas,,nice bearing common tumor suppressor gene mutations typically develop soft tissue sarcomas and lymphomas. One marked species distinction between human and mouse that bears on the predisposition to carcinogenesis lies in the radical differences in length and regulation of the telomere, nucleoprotein complexes that cap the ends of eukaryotic chromosomes. Recent cancer modeling studies in the telomerase knockout p53 mutant mice revealed that telomere dynamics might be relevant to carcinogenesis. In these mice there is a shift in the tumor spectrum towards epithelial carcinomas, and these cancers emerge with complex cytogenetic profiles classical for human carcinomas. In this m,iau, we suggest that the mechanism of fusion-bridge-breakage-translocation triggered by critically short telomeres, may be one of the generators of genomic instability commonly seen in human carcinomas. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIA NIH HHS [K08 AG001019] NR 117 TC 56 Z9 57 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD JUN PY 2001 VL 11 IS 3 BP 227 EP 238 DI 10.1006/scbi.2000.0374 PG 12 WC Oncology SC Oncology GA 447YW UT WOS:000169600900006 PM 11407947 ER PT J AU Yang, FC Merlino, G Chin, L AF Yang, FC Merlino, G Chin, L TI Genetic dissection of melanoma pathways in the mouse SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE melanoma; mouse model; 16(INK4a); p19(ARF); INK4; p53; RB; H-RAS(V12G) ID HUMAN-MALIGNANT MELANOMA; TUMOR-SUPPRESSOR GENE; HUMAN MELANOCYTIC LESIONS; CLINIC-BASED POPULATION; CUTANEOUS MELANOMA; CELL-CYCLE; FAMILIAL MELANOMA; P53 GENE; ULTRAVIOLET-RADIATION; GERMLINE MUTATIONS AB The frequent loss of the INK4a/ARF locus, encoding for both p16(INK4a) and p19(ARF) in, human melanoma, raises the question as to which INK4a/ARF gene product functions to suppress melanoma-genesis in vivo. Studies in the mouse have shown that activated RAS mutation can cooperate with INK4a(Delta2/3) deficiency (null for both p16(INK4a) and P19(ARF)) to promote development of melanoma, and these melanomas retain wild-type p53. Given the functional link between p19(ARF) and p53, we have shown shown that activated RAS can also cooperate with p53 deficiency to produce melanoma in the mouse Moreover, genome-wide analysis of RAS-induced p53 mutant melanomas reveals alterations of key components governing RB-regulated G1/S transition, such as c-Myc. These experimental findings suggest that both RE and p53 pathways function to suppress melanocyte transformation in vivo in the mouse. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Mayer448, Boston, MA 02115 USA. NR 73 TC 15 Z9 16 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD JUN PY 2001 VL 11 IS 3 BP 261 EP 268 DI 10.1006/scbi.2000.0376 PG 8 WC Oncology SC Oncology GA 447YW UT WOS:000169600900009 PM 11407950 ER PT J AU Lynch, TJ AF Lynch, TJ TI Review of two phase III randomized trials of single-agent docetaxel in previously treated advanced non-small cell lung cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID CHEMOTHERAPY; VINORELBINE; CISPLATIN C1 Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. RP Lynch, TJ (reprint author), Cox Bldg, Boston, MA 02114 USA. NR 18 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2001 VL 28 IS 3 SU 9 BP 5 EP 9 DI 10.1053/sonc.2001.24601 PG 5 WC Oncology SC Oncology GA 446DY UT WOS:000169498700002 PM 11444253 ER PT J AU Tejima, E Katayama, Y Suzuki, Y Kano, T Lo, EH AF Tejima, E Katayama, Y Suzuki, Y Kano, T Lo, EH TI Hemorrhagic transformation after fibrinolysis with tissue plasminogen activator - Evaluation of role of hypertension with rat thromboembolic stroke model SO STROKE LA English DT Article DE cerebral hemorrhage; fibrinolysis; hypertension; stroke; rats ID CEREBRAL INFARCTION; EMBOLIC STROKE; URGENT THERAPY; BLOOD; THROMBOLYSIS; MINUTES AB Background and Purpose - We used a rat model of thromboembolic stroke to evaluate whether hypertension increases the incidence of hemorrhage after fibrinolysis with tissue plasminogen activator (tPA). Methods - In this model, a microclot suspension was injected into the middle cerebral artery territory to induce focal ischemia. Reperfusion was induced in spontaneously hypertensive rats (SHR) by administering tPA (10 mg/kg) intravenously at 2 hours or 6 hours after the onset of thromboembolic focal ischemia. In untreated control rats, saline was administered at 2 hours after ischemia. Results - Hemorrhagic transformation was observed only in rats that received tPA at 6 hours (6 of 8 rats [75%]). Reduction of mean arterial blood pressure from 122 +/-3 to 99 +/-2 mm Hg with hydralazine, given to SHR for 1 week before ischemia, significantly decreased the incidence of hemorrhage in 2 of 11 rats (18%), tPA reduced infarct volumes, but cotreatment with hydralazine did not result in further protection. Conclusions - This study demonstrates that in this rat thromboembolic model of stroke, tPA-induced hemorrhage is dependent on blood pressure and that pharmacological reduction of hypertension during fibrinolysis can reduce the risk of hemorrhagic transformation. C1 Nihon Univ, Sch Med, Dept Neurol Surg, Tokyo, Japan. Massachusetts Gen Hosp, Neuroprotect Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Kano, T (reprint author), 30-1 Oyaguchi Kamimachi,Itabashi Ku, Tokyo 1738610, Japan. FU NINDS NIH HHS [R01-NS38731, R01-NS37074, R29-NS32806] NR 20 TC 36 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2001 VL 32 IS 6 BP 1336 EP 1340 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 440PZ UT WOS:000169184600021 PM 11387496 ER PT J AU Sarr, MG Warshaw, AL AF Sarr, MG Warshaw, AL TI Duplicate publication/duplicate submission - unfortunately still a problem SO SURGERY LA English DT Article C1 Mayo Clin & Mayo Fdn, Div Gastroenterol & Gen Surg, GI Res Unit, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Sarr, MG (reprint author), Mayo Clin & Mayo Fdn, Div Gastroenterol & Gen Surg, GI Res Unit, 200 1st St SW,A1 2-435, Rochester, MN 55905 USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2001 VL 129 IS 6 BP 653 EP 654 DI 10.1067/msy.2001.114551 PG 2 WC Surgery SC Surgery GA 440PR UT WOS:000169183900001 PM 11391359 ER PT J AU Stephen, AE Berger, DL AF Stephen, AE Berger, DL TI Carcinoma in the porcelain gallbladder: A relationship revisited SO SURGERY LA English DT Article ID ULTRASOUND; CANCER AB Background, Gallbladder cancer is the most common biliary tract malignancy. Calcification of the gallbladder wall is reported to be associated with gallbladder cancer In the literature, the incidence is quoted to be between 12% and 61%. This study, aims to clarify the msh of cancer in a calcified gallbladder. Methods. The charts and pathology reports at the Massachusetts General Hospital were reviewed and patients with either gallbladder cancer or a calcified gallbladder were included in the study. The Fisher exact test was used to test for the association between cancer and gallbladder wall calcifications. Results. From 1962 to 1999, there were approximately 25,900 gallbladder specimens analyzed at the Massachusetts General Hospital. There were 150 patients with gallbladder cancer and 44 patients with calcified gallbladders. Two types of calcified gallbladders were noted: those with complete intramural calcification (n = 17) and those With selective mucosal calcification (n = 27). The incidence of cancer arising in, a gallbladder with selective mucosal wall calcification was approximately 7%. There was a significant association between gallbladder cancer and selective mucosal calcification with an odds ratio of 13.89 (P = .01). There were no patients with diffuse intramural calcification and cancer. Conclusions. A calcified gallbladder is associated with an increased msk of gallbladder cancer, but at a much lower rate than previously estimated. The incidence of cancer depends on the pattern of calcification; selective mucosal calcification poses a significant risk of cancer whereas diffuse intramural calcification does not. C1 Massachusetts Gen Hosp, Dept Surg, ACC 465, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, ACC 465, 15 Parkman St, Boston, MA 02114 USA. NR 14 TC 81 Z9 83 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2001 VL 129 IS 6 BP 699 EP 703 DI 10.1067/msy.2001.113888 PG 5 WC Surgery SC Surgery GA 440PR UT WOS:000169183900009 PM 11391368 ER PT J AU Werner, J Saghir, M Castillo, CFD Warshaw, AL Laposata, M AF Werner, J Saghir, M Castillo, CFD Warshaw, AL Laposata, M TI Linkage of oxidative and nonoxidative ethanol metabolism in the pancreas and toxicity of nonoxidative ethanol metabolites for pancreatic acinar cells SO SURGERY LA English DT Article ID ACID ETHYL-ESTERS; TRYPSINOGEN-ACTIVATION PEPTIDES; LOW-DENSITY-LIPOPROTEIN; WHITE BLOOD-CELLS; ALCOHOL-DEHYDROGENASE; PROTEIN-SYNTHESIS; FATTY-ACIDS; RAT; ACETALDEHYDE; CHOLECYSTOKININ AB Background. Alcohol abuse is a major cause of pancreatic damage. Recent experimental evidence suggests that fatty acid ethyl esters (FAEE), nonoxidative ethanol metabolites, injure pancreatic acinar cells. Linkage between oxidative and nonoxidative metabolism of ethanol in the pancreas may contribute to increased FAEE levels. Methods. To study the association between oxidative and nonoxidative ethanol metabolism, FAEE concentration and FAEE synthase activity in rat pancreatic and liver homogenates incubated with ethanol were evaluated with and without inhibitors of oxidative ethanol metabolism. For toxicity studies, trypsinogen activation peptide synthesis as a measure of pancreatic cell injury was quantitated in unstimulated and cerulein-stimulated isolated pancreatic acinar cells incubated with ethanol or FAEE. Results. Inhibition of oxidative ethanol metabolism results in a 2- to 3-fold increase in nonoxidative ethanol metabolism to FAEE in pancreas and in liver. Both ethanol and FAEE induce increased intracellular trypsinogen activation by more than 50% in the presence of physiologic concentrations of cerulein in vitro. Conclusions. These findings demonstrate that the inhibition of oxidative ethanol metabolism results in an increase in flux through the nonoxidative pathway and support the proposition that alcohol-induced pancreatic injury is mediated at least in part by FAEE, which are important products of pancreatic ethanol metabolism. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, Room 506,White Bldg,55 Fruit St, Boston, MA 02114 USA. NR 53 TC 31 Z9 31 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2001 VL 129 IS 6 BP 736 EP 744 DI 10.1067/msy.2001.113891 PG 9 WC Surgery SC Surgery GA 440PR UT WOS:000169183900014 PM 11391373 ER PT J AU Nasser, SM Choudry, UH Nielsen, GP Ott, MJ AF Nasser, SM Choudry, UH Nielsen, GP Ott, MJ TI A leukemoid reaction in a patient with a dedifferentiated liposarcoma SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Ott, MJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, 626 Cox Bldg,100 Blossom St, Boston, MA 02114 USA. NR 4 TC 11 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD JUN PY 2001 VL 129 IS 6 BP 765 EP 767 DI 10.1067/msy.2001.109498 PG 3 WC Surgery SC Surgery GA 440PR UT WOS:000169183900020 PM 11391379 ER PT J AU Brown, JR Kuter, DJ AF Brown, JR Kuter, DJ TI The effect of unfractionated vs. low molecular weight heparin on tissue factor pathway inhibitor levels in hospital inpatients SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE heparin; dalteparin; tissue factor pathway inhibitor; extrinsic pathway; low molecular weight heparin ID COAGULATION INHIBITOR; FACTOR-XA; POSSIBLE MECHANISM; ENDOTHELIAL-CELLS; UNSTABLE ANGINA; ANTIGEN LEVELS; HUMAN-PLASMA; RELEASE; TFPI; THROMBOSIS AB Although heparin is widely used as an antithrombotic agent, its multiple mechanisms of action an not fully defined. Recent work has suggested that tissue factor pathway inhibitor (TFPI) may contribute to the antithrombotic activity of heparin by inhibiting the extrinsic pathway of coagulation. We have investigated the effect of heparin on TFPI and have found that when unfractionated heparin is given by continuous intravenous infusion to hospitalized inpatients. TFPI levels increase 2.3-fold and remain high as long as heparin is continued, but return to baseline levels soon after the infusion is stopped. In contrast, therapeutic doses of the low molecular weight heparin, dalteparin, resulted in significantly less TFPI induction. Given the increasing number of studies establishing the clinical efficacy of low molecular weight heparins as antithrombotic agents, these results suggest that TFPI may not be a major contributor to the antithrombotic effect of heparin. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Brown, JR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Med Housestaff,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL54838, HL61222] NR 39 TC 9 Z9 11 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 43, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUN PY 2001 VL 85 IS 6 BP 979 EP 985 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 446EM UT WOS:000169500000006 PM 11434705 ER PT J AU Snydman, DR Falagas, ME Avery, R Perlino, C Ruthazer, R Freeman, R Rohrer, R Fairchild, R O'Rourke, E Hibberd, P Werner, BG AF Snydman, DR Falagas, ME Avery, R Perlino, C Ruthazer, R Freeman, R Rohrer, R Fairchild, R O'Rourke, E Hibberd, P Werner, BG TI Use of combination cytomegalovirus immune globulin plus ganciclovir for prophylaxis in CMV-seronegative liver transplant recipients of a CMV-seropositive donor organ: A multicenter, open-label study SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT XXth Congress of the Scandinavian-Transplantation-Society CY MAY 11-12, 2001 CL HELSINKI, FINLAND SP Scandinavian Transplantat Soc ID HIGH-DOSE ACYCLOVIR; RANDOMIZED TRIAL; RISK-FACTORS; DISEASE; PREVENTION; INFECTION; THERAPY; ANTIBODY C1 New England Med Ctr, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Emory Univ, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts State Lib Inst, Boston, MA USA. RP Snydman, DR (reprint author), New England Med Ctr, 750 Washington St,Box 238, Boston, MA 02111 USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 22 TC 24 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD JUN PY 2001 VL 33 IS 4 BP 2571 EP 2575 DI 10.1016/S0041-1345(01)02101-7 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 445DL UT WOS:000169442800050 PM 11406251 ER PT J AU Albers, DS Augood, SJ AF Albers, DS Augood, SJ TI New insights into progressive supranuclear palsy SO TRENDS IN NEUROSCIENCES LA English DT Review ID RICHARDSON-OLSZEWSKI SYNDROME; ALPHA-SYNUCLEIN GENE; PARKINSONS-DISEASE; NEURODEGENERATIVE DISEASES; NITRIC-OXIDE; TAU-PROTEIN; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; NEUROFIBRILLARY DEGENERATION; CORTICOBASAL DEGENERATION AB Increased oxidative damage and mitochondrial dysfunction have been suggested to play crucial roles in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. In this review, we will focus on progressive supranuclear palsy (PSP), a rare parkinsonian disorder with tau pathology. Particular emphasis is placed on the genetic and biochemical data that has emerged, offering new perspectives into the pathogenesis of this devastating disease, especially the contributory roles of oxidative damage and mitochondrial dysfunction. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Albers, DS (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. NR 76 TC 41 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUN PY 2001 VL 24 IS 6 BP 347 EP 352 DI 10.1016/S0166-2236(00)01794-X PG 6 WC Neurosciences SC Neurosciences & Neurology GA 433NK UT WOS:000168766300026 PM 11356507 ER PT J AU Barry, MJ AF Barry, MJ TI Impact of medical therapy on transurethral resection of the prostate: A decade of change - Editorial comment SO UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD JUN PY 2001 VL 57 IS 6 BP 1085 EP 1086 DI 10.1016/S0090-4295(01)01019-6 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 435MB UT WOS:000168884300019 ER PT J AU Ma, ZF Wang, ZY Zhang, JR Gong, P Chen, HL AF Ma, ZF Wang, ZY Zhang, JR Gong, P Chen, HL TI Carcinogenic potential of duodenal reflux juice from patients with long-standing postgastrectomy SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PROTEIN-KINASE-C; PEPTIC-ULCER SURGERY; STOMACH-CANCER; BILE-ACIDS; SIGNAL TRANSDUCTION; CELL-TRANSFORMATION; PARTIAL GASTRECTOMY; BENIGN CONDITIONS; AMSTERDAM COHORT; GASTRIC-SURGERY AB AIM To determine whether study on the carcinogenic potential of reflux juice from patients with remote gastrectomy could clarify the inherent relationship between duodenal reflux and gastric stump cancer. METHODS A total of 37 reflux juice samples (13 Billroth I. 24 Billroth II) were employed in the present study. A two - stage transformation assay using BALB/c 3T3 cells was carried out to test the initiating or promoting activity of these samples. RESULTS Two of IS ( 11. 1%) ref lux samples exerted initiating activities. whereas 9/ 19 (47. 4%) samples enhanced the MNNG-initiating cell transformation, suggesting the duodenal reflux juice might more frequently possess the tumor-promoter activity (P = 0. 029). In addition, there was no difference in initiating activities of the samples irrespective of surgical procedures (P=0. 488), while Billroth II samples exhibited stronger tumor-promoter activity than Billroth I samples (P = 0. 027). Furthermore, the promoter activities were well correlated with the histological changes of the stomas ( r(s) = 0. 625, P = 0. 004), but neither their cytotoxicities nor initiating activities had this correlation ( Probabilities were 0. 523 and 0. 085, respectively). CONCLUSION The duodenal reflux juice from patients with remote postgastrectomy did have carcinogenic potential, and suggested that tumor-promoting activity should principally account for the high incidence of gastric cancer in gastrectomy patients. In contrast, it is difficult to explain the high stump-cancer incidence with the " N-nitroso compounds " theory-a popular theory for the intact stomach carcinogenesis, and it seemed to be justified to focus chemoprevention of this cancer on the tumor-promoting potential of reflux juice. C1 Dalian Med Univ, Hosp 1, Dept Gen Surg, Dalian 116011, Peoples R China. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Ma, ZF (reprint author), Dalian Med Univ, Hosp 1, Dept Gen Surg, Dalian 116011, Peoples R China. NR 51 TC 9 Z9 11 U1 0 U2 1 PU W J G PRESS PI BEIJING PA PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JUN PY 2001 VL 7 IS 3 BP 376 EP 380 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 461NU UT WOS:000170371000015 PM 11819793 ER PT J AU Harris, RS Mark, EJ AF Harris, RS Mark, EJ TI A 42-year-old man with multiple pulmonary cysts and recurrent respiratory infections. Sjogren's syndrome involving the lungs, with follicular bronchiolitis, air trapping with cyst formation, and deposition of amyloid-like material. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LYMPHOCYTIC INTERSTITIAL PNEUMONIA; HIGH-RESOLUTION CT; BRONCHIAL HYPERREACTIVITY; MALIGNANT-LYMPHOMA; DISEASE; INVOLVEMENT; SCLEROSIS; BULLAE C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Harris, RS (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 31 PY 2001 VL 344 IS 22 BP 1701 EP 1708 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 436YG UT WOS:000168963000008 ER PT J AU Yildiz, A Sachs, GS Dorer, DJ Renshaw, PF AF Yildiz, A Sachs, GS Dorer, DJ Renshaw, PF TI P-31 Nuclear magnetic resonance spectroscopy findings in bipolar illness: a meta-analysis SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE phosphomonoesters; phosphodiesters; brain phosphorous metabolism ID BRAIN PHOSPHORUS-METABOLISM; HIGH-ENERGY PHOSPHATE; TEMPORAL LOBES; MOOD DISORDERS; SCHIZOPHRENIA; LESIONS; MANIA; REDUCTION; REGION; CORTEX AB Published literature comparing P-31 MR brain spectra of bipolar patients to healthy controls was evaluated, focusing on phosphomonoester (PME)/phosphodiester (PDE) resonance areas because these metabolites are related to membrane phospholipids and membrane defects in bipolar disorder have been suggested. Studies comparing PME: and/or PDE values of bipolar subjects to values observed in healthy controls were reviewed. Data from the studies meeting our inclusion criteria (8 reports involving 139 bipolar and 189 comparison subjects) were grouped according to the mood state of the subjects. Meta-analyses of data were performed to compare PME and PDE levels of euthymic bipolar patients to healthy controls, as well as comparing PME levels during euthymia in bipolar subjects to values observed during manic and depressed states. The PME values of euthymic bipolar patients were found to be significantly lower than PME values of healthy controls. Depressed bipolar patients had significantly higher PME values in comparison to euthymic bipolar patients. No significant difference could be detected between the PDE values of bipolars and controls. This meta-analysis found support for trait- and possibly state-dependent abnormalities of membrane phospholipid metabolism, which may reflect a dysregulation in brain signal transduction systems of relevance in bipolar illness. (C) 2001 Elsevier Science Ireland Ltd. All rights: reserved. C1 Dokuz Eylul Med Sch, Dept Psychiat, Izmir, Turkey. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bipolar Program, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. RP Yildiz, A (reprint author), 170 Sok Guller Apt 8-8,PK 35360, Izmir, Turkey. FU NIMH NIH HHS [MH 58681] NR 44 TC 45 Z9 46 U1 1 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD MAY 30 PY 2001 VL 106 IS 3 BP 181 EP 191 DI 10.1016/S0925-4927(01)00082-8 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 442PA UT WOS:000169293100004 PM 11382540 ER PT J AU Cardenas, VA Ezekiel, F Di Sclafani, V Gomberg, B Fein, G AF Cardenas, VA Ezekiel, F Di Sclafani, V Gomberg, B Fein, G TI Reliability of tissue volumes and their spatial distribution for segmented magnetic resonance images SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE K-means clustering; magnetic resonance image; brain; image processing; tissue classification ID POSITRON-EMISSION-TOMOGRAPHY; GRAY-MATTER; AUTOMATED ALGORITHM; MR-IMAGES; BRAIN; VALIDATION; CLASSIFICATION; REGISTRATION AB Before using MRI tissue segmentation in clinical studies as a dependent variable or as a means to correct functional data for differential tissue contribution, we must first establish the volume reliability and spatial distribution reproducibility of the segmentation method. Although several reports of volume reliability can be found in the literature, there are no articles assessing the reproducibility of the spatial distribution of tissue. In this report, we examine the validity, volume reliability, and spatial distribution reproducibility for our K-means cluster segmentation. Validation was examined by classifying gray matter, white matter, and CST: on images constructed using an MRI simulator and digital brain phantom, with percentage volume differences of less than 5% and spatial distribution overlaps greater than 0.94 (1.0 is perfect). We also segmented repeat scan MRIs from 10 healthy subjects, with intraclass correlation coefficients greater than 0.92 for cortical gray matter, white matter, sulcal CSF, and ventricular CSF. The original scans were also coregistered to the repeat scan of the same subject, and the spatial overlap for each tissue was then computed. Our overlaps ranged from 0.75 to 0.86 fur these tissues. Our results support the use of K-means cluster segmentation, and the use of segmented structural MRIs to guide the analysis of functional and other images. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Penn, Med Ctr, Dept Bioengn, Philadelphia, PA 19004 USA. Neurobehav Res Inc, Corte Madera, CA 94925 USA. RP Univ Calif San Francisco, Dept Radiol, 4150 Clement St, San Francisco, CA 94121 USA. EM valerie@itsa.ucsf.edu FU NIA NIH HHS [AG12435]; NIAAA NIH HHS [P01AA11493]; NIDA NIH HHS [R01DA08365] NR 25 TC 37 Z9 39 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 EI 1872-7506 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD MAY 30 PY 2001 VL 106 IS 3 BP 193 EP 205 DI 10.1016/S0925-4927(01)00075-0 PG 13 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 442PA UT WOS:000169293100005 PM 11382541 ER PT J AU Farley, RA Elquza, E Muller-Ehmsen, J Kane, DJ Nagy, AK Kasho, VN Faller, LD AF Farley, RA Elquza, E Muller-Ehmsen, J Kane, DJ Nagy, AK Kasho, VN Faller, LD TI (18)O-exchange evidence that mutations of arginine in a signature sequence for P-type pumps affect inorganic phosphate binding SO BIOCHEMISTRY LA English DT Article ID FLUORESCEIN 5'-ISOTHIOCYANATE MODIFICATION; SITE-DIRECTED MUTAGENESIS; PLASMA-MEMBRANE ATPASE; SARCOPLASMIC-RETICULUM; AMINO-ACIDS; ADENOSINE-TRIPHOSPHATASE; FUNCTIONAL CONSEQUENCES; STEREOCHEMICAL COURSE; ENERGY TRANSDUCTION; ANGSTROM RESOLUTION AB We have proposed a model for part of the catalytic site of P-type pumps in which arginine in a signature sequence functions like lysine in P-loop-containing enzymes that catalyze adenosine 5'-triphosphate hydrolysis [Smirnova, I. N., Kasho, V. N., and Faller, L. D. (1998) FEES Lett. 431, 309-314]. The model originated with evidence from site-directed mutagenesis that aspartic acid in the DPPR sequence of Na,K-ATPase binds Mg(2+) [Farley, R. A., et al. (1997) Biochemistry 36, 941-951]. It was developed by assuming that the catalytic domain of P-type pumps evolved from enzymes that catalyze phosphoryl group transfer. The functions of the positively charged amino group in P-loops are to bind substrate and to facilitate nucleophilic attack upon phosphorus by polarizing the gamma -phosphorus-oxygen bond. To test the prediction that the positively charged guanidinium group of R596 in human alpha (1) Na,K-ATPase participates in phosphoryl group transfer, the charge was progressively decreased by site-directed mutagenesis. Mutants R596K, -Q, -T, -M, -A, -G, and -E were expressed in yeast membranes, and their ability to catalyze phosphorylation with inorganic phosphate was evaluated by following (18)O exchange. R596K, in which the positive charge is retained, resembled the wild type. Substitution of a negative charge (R596E) resulted in complete loss of activity. The remaining mutants with uncharged side chains had both lowered affinity for inorganic phosphate and altered phosphate isotopomer distributions, consistent with increased phosphate-off rate constants compared to that of the wild type. Therefore, mutations of R596 strengthen our hypothesis that the oppositely charged side chains of the DPPR peptide in Na,K-ATPase form a quaternary complex with magnesium phosphate. C1 Univ Calif Los Angeles, Sch Med, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ So Calif, Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Faller, LD (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. EM lfaller@ucla.edu FU NIDDK NIH HHS [DK52802] NR 52 TC 6 Z9 6 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 29 PY 2001 VL 40 IS 21 BP 6361 EP 6370 DI 10.1021/bi010270 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 436GC UT WOS:000168927300020 PM 11371198 ER PT J AU Oesterle, SN Reifart, N Hauptmann, E Hayase, M Yeung, AC AF Oesterle, SN Reifart, N Hauptmann, E Hayase, M Yeung, AC TI Percutaneous in situ coronary venous arterialization - Report of the first human catheter-based coronary artery bypass SO CIRCULATION LA English DT Article ID TRANSMYOCARDIAL LASER REVASCULARIZATION; REFRACTORY ANGINA; RANDOMIZED TRIAL; MEDICAL THERAPY; GENE-THERAPY; ANGIOGENESIS; MYOCARDIUM; DISEASE AB Diffuse coronary artery disease is frequently untreatable by coronary artery bypass or angioplasty. Many such "no-option" patients have been subjects for trials of angiogenesis using growth factor manipulation or laser injury. We think these novel revascularization strategies are limited by insufficient inflow to putative areas of new microvasculature and thus seek a more mechanical solution. We report the use of a catheter-based system for arterializing the adjacent anterior cardiac vein in a patient with chronic total occlusion of the left anterior descending coronary artery. A composite catheter system (phased-array ultrasound imaging system mounted on a catheter with extendable nitinol needle) was used to deliver an exchange-length intracoronary guidewire from the proximal left anterior descending coronary artery into the parallel anterior interventricular vein. Using standard angioplasty techniques, a fistula was then constructed from the proximal artery to the coronary vein using a self-expanding connector. The proximal vein was blocked with a novel self-expanding "blocker," thus precluding "steal" through the coronary sinus and forcing retroperfusion of the anterior wall. The procedure was completed without complication, and a follow-up angiogram at 3 months confirmed continued patency of the arteriovenous connection. This patient, who had severe angina before the procedure, has been asymptomatic for 12 months, Percutaneous in situ venous arterialization may be an effective therapy for diffuse, "untreatable" coronary disease by supplying a robust inflow of arterialized blood via retroperfusion to severely ischemic myocardium. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Invas Cardiol Serv, Boston, MA 02114 USA. Kardiol Inst, Bad Soden, Germany. Krankenhaus Barmherzigen Bruder, Trier, Germany. Toyohashi Heart Ctr, Toyohashi, Aichi, Japan. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Oesterle, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Invas Cardiol Serv, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 24 TC 44 Z9 52 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2001 VL 103 IS 21 BP 2539 EP 2543 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 437UW UT WOS:000169012800014 PM 11382720 ER PT J AU Friederich, PW Levi, M Bauer, KA Vlasuk, GP Rote, WE Breederveld, D Keller, T Spataro, M Barzegar, S Buller, HR AF Friederich, PW Levi, M Bauer, KA Vlasuk, GP Rote, WE Breederveld, D Keller, T Spataro, M Barzegar, S Buller, HR TI Ability of recombinant factor VIIa to generate thrombin during inhibition of tissue factor in human subjects SO CIRCULATION LA English DT Article DE anticoagulants; coagulation; thrombosis; drugs; inhibitors ID FACTOR PATHWAY INHIBITOR; ACTIVATED FACTOR-VII; HUMAN ATHEROSCLEROTIC PLAQUES; FACTOR-IX; FACTOR-X; BLOOD-COAGULATION; PROTEIN-C; MECHANISM; HEMOPHILIA; PATIENT AB Background-In view of the central role of the tissue factor-factor VIIa pathway in the initiation of blood coagulation, novel therapeutic strategies aimed at inhibiting this catalytic complex are currently being evaluated. A limitation of this new class of anticoagulants may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs. The aim of this study was to investigate the in vivo potential of recombinant factor VIIa (rVIIa) to induce thrombin generation in healthy subjects pretreated with recombinant nematode anticoagulant protein c2, a specific inhibitor of the tissue factor-factor VIIa complex, in a double-blind randomized crossover study. Methods and Results-Administration of nematode anticoagulant protein c2 (3.5 mug/kg) caused a prolongation of the prothrombin time from 13.7+/-0.6 to 16.9+/-1.2 seconds. The subsequent injection of rVIIa (90 mug/kg) resulted in an immediate and complete correction of the prothrombin time and a marked generation of thrombin, reflected by increased levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes from 0.75+/-0.64 to 3.29+/-6.3 nmol/L and from 2.4+/-0.6 to 10.7+/-3.9 mug/mL, respectively. Factor X and IX activation peptides showed a 3.5-fold and a 3.8-fold increase, respectively, after the administration of rVIIa in the presence of nematode anticoagulant protein c2. Conclusions-During treatment with an inhibitor of the tissue factor-factor VIIa complex, the infusion of rVIIa resulted in thrombin generation. Our results indicate that rVIIa may be a good candidate as an antidote for inhibitors of tissue factor. C1 Univ Amsterdam, Acad Med Ctr, Dept Vasc Med & Internal Med F4, NL-1105 AZ Amsterdam, Netherlands. Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Corvas Int Inc, San Diego, CA USA. RP Levi, M (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Vasc Med & Internal Med F4, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. NR 29 TC 62 Z9 63 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2001 VL 103 IS 21 BP 2555 EP 2559 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 437UW UT WOS:000169012800017 PM 11382723 ER PT J AU Scalia, R Gooszen, ME Jones, SP Hoffmeyer, M Rimmer, DM Trocha, SD Huang, PL Smith, MB Lefer, AM Lefer, DJ AF Scalia, R Gooszen, ME Jones, SP Hoffmeyer, M Rimmer, DM Trocha, SD Huang, PL Smith, MB Lefer, AM Lefer, DJ TI Simvastatin exerts both anti-inflammatory and cardioprotective effects in apolipoprotein E-deficient mice SO CIRCULATION LA English DT Article DE endothelium; hypercholesterolemia; reperfusion; nitric oxide ID NITRIC-OXIDE SYNTHASE; REDUCTASE INHIBITORS; P-SELECTIN; ACUTE HYPERCHOLESTEROLEMIA; CHOLESTEROL; ENDOTHELIUM; DISEASE; RABBITS; REPERFUSION; STATINS AB Background-Simvastatin attenuates ischemia and reperfusion in normocholesterolemic animals by stabilizing endothelial nitric oxide synthase activity and inhibiting neutrophil-mediated injury. Because endothelial dysfunction is a detrimental effect of hypercholesterolemia, we examined whether short-term treatment with simvastatin could inhibit leukocyte-endothelium interaction and attenuate myocardial ischemia-reperfusion injury in apoE-deficient (apoE(-/-)) mice fed a high-cholesterol diet. Methods and Results-We studied leukocyte-endothelium interactions in apoE(-/-) mice fed a normal or a high-cholesterol diet after short-term (ie, 18 hours) simvastatin treatment. We also studied simvastatin treatment in myocardial ischemia-reperfusion injury by subjecting apoE(-/-) mice to 30 minutes of ischemia and 24 hours of reperfusion. ApoE(-/-) mice fed a high-cholesterol diet exhibited higher blood cholesterol levels, which were not affected by short-term simvastatin treatment. However, the increased leukocyte rolling and adherence that occurred in cholesterol-fed apoE(-/-) mice (P<0.001 versus control diet) were significantly attenuated by simvastatin treatment (P<0.01 versus vehicle). Cholesterol-fed apoE(-/-) mice subjected to myocardial ischemia-reperfusion also experienced increased myocardial necrosis (P<0.01 versus control diet), which was significantly attenuated by simvastatin (P<0.01 versus vehicle). Simvastatin therapy also significantly increased vascular nitric oxide production in apoE(-/-) mice. Conclusions-Simvastatin attenuates leukocyte-endothelial cell interactions and ameliorates ischemic injury in hypercholesterolemic mice independently of lipid-lowering actions. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Physiol, Philadelphia, PA 19107 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA USA. RP Lefer, DJ (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, 1501 Kings Highway, Shreveport, LA 71130 USA. RI Lefer, David/A-6372-2012; Jones, Steven/D-5092-2009 OI Jones, Steven/0000-0001-5376-8089 FU NHLBI NIH HHS [R01-HL-60849]; NIDDK NIH HHS [P01-DK-43785] NR 29 TC 152 Z9 163 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 29 PY 2001 VL 103 IS 21 BP 2598 EP 2603 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 437UW UT WOS:000169012800024 PM 11382730 ER PT J AU Chen, SY Wilkemeyer, MF Sulik, KK Charness, ME AF Chen, SY Wilkemeyer, MF Sulik, KK Charness, ME TI Octanol antagonism of ethanol teratogenesis SO FASEB JOURNAL LA English DT Article DE fetal alcohol syndrome; L1 cell adhesion molecule; alcohol, ethyl; fetal development; apoptosis ID FETAL ALCOHOL SYNDROME; CEREBELLAR GRANULE NEURONS; ADHESION MOLECULES L1; CELL-CELL ADHESION; NEURAL CREST CELLS; POTASSIUM CHANNELS; FREE-RADICALS; DEATH; INHIBITION; APOPTOSIS AB Alcohol may cause birth defects in part by disrupting the developmentally critical L1 cell adhesion molecule. Because 1-octanol antagonizes ethanol inhibition of L1-mediated cell adhesion, we asked whether 1-octanol also prevents ethanol teratogenicity. L1 was detected in control mouse embryos as early as gestational day 8 (GD8), an early stage of vulnerability to ethanol teratogenesis. Culture of GD8 embryos with ethanol increased apoptotic cell death and decreased numbers of somite pairs. 1-Octanol markedly reduced both ethanol effects. The paradoxical inhibition of ethanol teratogenicity by a longer chain 1-alcohol suggests a strategy for developing compounds that prevent alcohol-related birth defects. C1 Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. VA Boston Healthcare Syst, Neurol Serv, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Charness, ME (reprint author), Harvard Med Sch, VA Boston Healthcare Syst, Dept Neurol 127, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM mcharness@hms.harvard.edu NR 41 TC 42 Z9 42 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY 29 PY 2001 VL 15 IS 7 BP 1649 EP + DI 10.1096/fj.00-0862fje PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 519CQ UT WOS:000173707700011 PM 11427515 ER PT J AU Womer, KL Sayegh, MH Auchincloss, H AF Womer, KL Sayegh, MH Auchincloss, H TI Involvement of the direct and indirect pathways of allorecognition in tolerance induction SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Review DE direct pathway; indirect pathway; tolerance; transplantation; MHC peptides; allorecognition ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL RECOGNITION; ACQUIRED THYMIC TOLERANCE; ANTIGEN-PRESENTING CELLS; HOST DENDRITIC CELLS; RAT-LIVER ALLOGRAFTS; TOXIC LYMPHOCYTES-T; CLASS-I PEPTIDE; MHC PEPTIDES; TRANSPLANTATION TOLERANCE AB It is generally accepted that there are two pathways of allorecognition, direct and indirect, that together contribute to allograft rejection. Although it has been suggested that the direct pathway predominates during early acute rejection and that the indirect pathway provides a continuous supply of alloantigen responsible for chronic rejection, the true relative contribution of each pathway to the overall rejection process is still not entirely known. It is clear, however, that any strategies designed to achieve the ultimate goal in transplantation, the induction of tolerance, will need to take into account both pathways. This review seeks to explore the involvement of the direct and indirect pathways of allorecognition on a mechanistic level as it relates to the induction of tolerance. A brief historical perspective is included for each pathway as well as a comprehensive review of the mechanisms felt to be active during tolerance induction. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Renal,Lab Immunogenet & Transplantat, Boston, MA 02115 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, GRB 504, Boston, MA 02114 USA. NR 103 TC 25 Z9 25 U1 1 U2 2 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD MAY 29 PY 2001 VL 356 IS 1409 BP 639 EP 647 DI 10.1098/rstb.2001.0843 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 443TT UT WOS:000169357600005 PM 11375067 ER PT J AU Sykes, M Sachs, DH AF Sykes, M Sachs, DH TI Mixed chimerism SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Review DE tolerance; mixed chimera; bone marrow transplantation; xenotransplantation; natural antibodies; natural killer cells ID BONE-MARROW TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL DEPLETION; TOTAL LYMPHOID IRRADIATION; HEMATOPOIETIC STEM-CELLS; DONOR-SPECIFIC TOLERANCE; NATURAL-KILLER-CELLS; PORCINE ENDOTHELIAL-CELLS; WHOLE-BODY IRRADIATION; VS-HOST DISEASE AB Induction of mixed chimerism has the potential to overcome the current limitations of transplantation, namely chronic rejection, complications of immunosuppressive e therapy and the need for xenografts to overcome the current shortage of allogeneic organs. Successful achievement of mixed chimerism had been shown to tolerize T cells, B cells and possibly natural killer cells, the lymphocyte subsets that pose major barriers to allogeneic and xenogeneic transplants. Current understanding of the mechanisms involved in tolerization of each cell type is reviewed. Considerable advances have bet II made in reducing the potential toxicity of conditioning regimens required for the induction of mixed chimerism in rodent models, and translation of these strategies to large animal models and in a patient are important advances toward more widespread clinical application of the mixed chimerism approach for tolerance induction. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Surg Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Surg Serv, Boston, MA 02129 USA. FU NHLBI NIH HHS [P01 HL186461, R0HL63430, R01HL54038, R01HL63474, R01HL49915]; NIAID NIH HHS [R01AI37692] NR 194 TC 46 Z9 52 U1 0 U2 0 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD MAY 29 PY 2001 VL 356 IS 1409 BP 707 EP 726 DI 10.1098/rstb.2001.0853 PG 20 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 443TT UT WOS:000169357600012 PM 11375074 ER PT J AU Womer, KL Lee, RS Madsen, JC Sayegh, MH AF Womer, KL Lee, RS Madsen, JC Sayegh, MH TI Tolerance and chronic rejection SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Review DE chronic allograft nephropathy; chronic allograft dysfunction; transplantation; tolerance; chronic rejection; alloantigen ID RENAL-ALLOGRAFT REJECTION; KIDNEY-TRANSPLANT RECIPIENTS; ANTIGEN-SPECIFIC HYPOREACTIVITY; COLD ISCHEMIA/REPERFUSION INJURY; CONVERTING ENZYME-INHIBITION; LIVING UNRELATED DONORS; HUMAN CYTOMEGALO-VIRUS; T-CELL APOPTOSIS; IN-VIVO; MONOCLONAL-ANTIBODY AB The most common cause of chronic allograft loss is an incompletely understood clinicopathological entity called chronic rejection (CR). Recent reports suggest an improvement in long-term renal allograft survival, although it is not clear from these data whether a true reduction of biopsy-proven CR has occurred. Although newer immunosupressive medications have e greatly reduced the incidence of acute rejection (AR) in the early post-transplantation period the ideal therapy for both AR and CR would be to achieve a state of tolerance. By definition, such a state should allow for indefinite allograft survival, with no histopathological evidence of CR, despite immunocompetence in the host (i.e. without the need for chronic immunosupression). Although several experimental studies are able to achieve tolerance, with clear improvement in allograft survival, detailed studies on graft function and morphology are often not included. This review will discuss possible ways that tolerance induction could lead to a CR-free state. General mechanisms of CR and transplantation tolerance induction are discussed as well as the difficulties in translating small animals studies into large animals and humans. C1 Brigham & Womens Hosp, Div Renal, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Sayegh, MH (reprint author), Brigham & Womens Hosp, Div Renal, Lab Immunogenet & Transplantat, 75 Francis St, Boston, MA 02115 USA. NR 143 TC 26 Z9 30 U1 1 U2 1 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD MAY 29 PY 2001 VL 356 IS 1409 BP 727 EP 738 DI 10.1098/rstb.2001.0852 PG 12 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 443TT UT WOS:000169357600013 PM 11375075 ER PT J AU Richardson, RD Engel, CC McFall, M McKnight, K Boehnlein, JK Hunt, SC AF Richardson, RD Engel, CC McFall, M McKnight, K Boehnlein, JK Hunt, SC TI Clinician attributions for symptoms and treatment of Gulf War-related health concerns SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Conference on Identifying Effective Treatments for Gulf War Veterans Health Problems CY AUG 14, 2000 CL WASHINGTON, D.C. ID UNEXPLAINED SYMPTOMS; MEDICAL-CARE; CHRONIC PAIN; PATIENT; ILLNESS; PHYSICIAN; FATIGUE; ABUSE AB Background: Several clinical syndromes are defined solely on the basis of symptoms, absent an identifiable medical etiology. When evaluating and treating individuals with these syndromes, clinicians' beliefs might shape decisions regarding referral, diagnostic testing, and treatment. To assess clinician beliefs about the etiology and treatment of "Gulf War illness," we surveyed a sample of general internal medicine clinicians (GIMCs) and mental health clinicians (MHCs). Methods: Clinicians (77 GIMCs and 214 MHCs) at the Veterans Affairs Puget Sound Health Care System, Seattle, Wash, and the Veterans Affairs Medical Center in Portland, Ore, responded to a mailed survey of their beliefs about Gulf War illness. Results: Compared with GIMCs, MHCs were more likely to believe that Gulf War illness was the result of a "physical disorder" and that symptoms resulted from viruses or bacteria, immunizations, exposure to toxins, chemical weapons, or a combination of toxins and stress (P < .05). Conversely, GIMCs were more likely than MHCs to believe that Gulf War illness was a "mental disorder" and that symptoms were due to stress or posttraumatic stress disorder (P<.05). In addition, MHCs were more likely to endorse biological interventions to treat Gulf War illness (P.01), whereas GIMCs were more likely to endorse psychological interventions. Conclusion: Clinicians' beliefs about the etiology and effective treatment of Gulf War illness vary and thus might contribute to the multiple referrals often reported by Gulf War veterans. Health care models for Gulf War veterans and others with symptom-based disorders necessitate collaborative,interdisciplinary approaches. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Deployment Hlth Clin Ctr, Washington, DC 20307 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. Vet Affairs Med Ctr, Portland, OR USA. RP Richardson, RD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 23 TC 15 Z9 15 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 28 PY 2001 VL 161 IS 10 BP 1289 EP 1294 DI 10.1001/archinte.161.10.1289 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 434JN UT WOS:000168811500004 PM 11371256 ER PT J AU Asch, SM Kerr, EA Lapuerta, P Law, A McGlynn, EA AF Asch, SM Kerr, EA Lapuerta, P Law, A McGlynn, EA TI A new approach for measuring quality of care for women with hypertension SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Cardiology CY MAR 12-15, 2000 CL ANAHEIM, CALIFORNIA SP Amer Coll Cardiol ID BLOOD-PRESSURE; UNITED-STATES; HEALTH-CARE; SYSTEM; MANAGEMENT; POPULATION; PHYSICIANS AB Background: Guidelines for care of hypertensive patients have proliferated recently, yet quality assessment remains difficult in the absence of well-defined measurement systems. Existing systems have not always linked process measures to blood pressure outcomes. Methods: A quality measurement system was developed and tested on hypertensive women in a West Coast health plan. An expert panel selected clinically detailed, evidence-explicit indicators using a modified Delphi method. Thirteen indicators (1 screening, 5 diagnostic, 5 treatment, and 2 follow-up indicators) were selected by this process. Trained nurses used a laptop-based tool to abstract data from medical records for the most recent 2 years of care. Results: Of 15 004 eligible patients with hypertensive and other chronic disease codes, 613 patients were sampled, all eligible for the screening indicator. Of these, 234 women with an average blood pressure of 140/90 mm Hg or more, or a documented diagnosis of hypertension, were studied for the remaining indicators. The average woman received 64% of the recommended care. Most patients did not receive adequate initial history, physical examination, or laboratory tests. Only 37% of hypertensive women with persistent elevations to more than 160/90 mm Hg had changes in therapy or lifestyle recommended. The average adherence proportion to all indicators was lower in patients with uncontrolled blood pressure (> 140/90 mm Hg) than in those with controlled blood pressure (54% vs 73%; P < .001). Conclusions: Quality of hypertensive care falls short of indicators based on randomized controlled trials and national guidelines. Poor performance in essential care processes is associated with poor blood pressure control. C1 RAND Corp, Ctr Res Qual Hlth Care, Santa Monica, CA 90407 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. Vet Affairs Ctr Practice Management & Outcomes Re, Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Western Univ Hlth Sci, Pomona, CA USA. RP Asch, SM (reprint author), RAND Corp, Ctr Res Qual Hlth Care, 1700 Main St, Santa Monica, CA 90407 USA. NR 21 TC 39 Z9 40 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 28 PY 2001 VL 161 IS 10 BP 1329 EP 1335 DI 10.1001/archinte.161.10.1329 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 434JN UT WOS:000168811500010 PM 11371262 ER PT J AU Utsugi, R Barth, RN Lee, RS Kitamura, H LaMattina, JC Ambroz, J Sachs, DH Yamada, K AF Utsugi, R Barth, RN Lee, RS Kitamura, H LaMattina, JC Ambroz, J Sachs, DH Yamada, K TI Induction of transplantation tolerance with a short course of tacrolimus (FK506) I. Rapid and stable tolerance to two-haplotype fully MHC-mismatched kidney allografts in miniature swine SO TRANSPLANTATION LA English DT Article ID CLASS-II GENES; PRIMARILY VASCULARIZED ALLOGRAFTS; MAJOR HISTOCOMPATIBILITY COMPLEX; DISPARATE RENAL-ALLOGRAFTS; LIVER-TRANSPLANTATION; ORGAN-TRANSPLANTATION; RANDOMIZED TRIAL; T-CELLS; CYCLOSPORINE; SURVIVAL AB Background. Inbred miniature swine provide a large animal model in which the effects of selective major histocompatibility complex (MHC) matching can be reproducibly studied. We have previously demonstrated that although a 12-day course of cyclosporine uniformly induces tolerance to class I-mismatched renal allografts, it does not induce tolerance across full MHC barriers. In this study, we assessed whether and at what dose tacrolimus might permit allografts to induce tolerance across different MHC barriers. Methods. Recipients of MHC disparate renal allografts were treated with a 12-day course of tacrolimus by continuous intravenous infusion, Groups were divided as follows: (1) class I-mismatched kidneys with 0.3 mg/kg/day tacrolimus (n=3); (2) fully MHC-mismatched kidneys with 0.3 mg/kg/day tacrolimus (n=2); and (3) fully MHC-mismatched kidneys with 0.12-0.16 mg/kg/day tacrolimus (n=4). Results. In groups 1 and 2, recipients with tacrolimus levels of 45-80 ng/ml accepted renal allografts long-term with stable renal function. Donor-specific hyporesponsiveness was demonstrated by cell-mediated lymphocytotoxicity and mixed lymphocyte response, and subsequent donor-matched grafts were also accepted, without further immunosuppression (n=4), confirming systemic tolerance, In group 3, recipients that, achieved tacrolimus levels of 35 ng/ml (n=2) accepted their grafts without chronic changes, whereas recipients with levels of 20-26 ng/ml (n=2) developed chronic allograft glomerulopathy, suggesting 35 ng/ml as the threshold blood level for tolerance induction. In vitro assays demonstrated that peripheral blood lymphocytes from tolerant animals produced inhibitory cytokines, suggesting the involvement of regulatory mechanisms. Conclusions. To our knowledge, this study represents the first demonstration of the induction of transplant tolerance across a two-haplotype full MHC barrier with a short course of immunosuppression in a large animal model. These studies may also have clinical applicability, because the time course required to induce tolerance was sufficiently short that the high drug levels required might be expected to be tolerated clinically with only transient toxicity. C1 Harvard Univ, Transplatat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Yamada, K (reprint author), Harvard Univ, Transplatat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. RI Barth, Rolf/B-2542-2014; LaMattina, John/B-2976-2014 OI LaMattina, John/0000-0001-7016-0382 FU NHLBI NIH HHS [2PO1 HL18646-23]; NIAID NIH HHS [2RO1 AI31046-10] NR 50 TC 51 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 27 PY 2001 VL 71 IS 10 BP 1368 EP 1379 DI 10.1097/00007890-200105270-00003 PG 12 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 439DK UT WOS:000169095400003 PM 11391221 ER PT J AU Huang, JS Rietschel, P Hadigan, CM Rosenthal, DI Grinspoon, S AF Huang, JS Rietschel, P Hadigan, CM Rosenthal, DI Grinspoon, S TI Increased abdominal visceral fat is associated with reduced bone density in HIV-infected men with lipodystrophy SO AIDS LA English DT Article DE HIV; antiretroviral therapy; lipodystrophy; bone density ID IMMUNODEFICIENCY-VIRUS INFECTION; ANTIRETROVIRAL THERAPY; QUANTITATIVE CT; MINERAL DENSITY; WOMEN AB Objective: To examine the relationship between bone density and changes in regional and whole body composition in HIV-infected men with and without lipodystrophy. Design: Cross-sectional, observational study of HIV-infected men with and without lipodystrophy and matched HIV-negative controls. Setting: Tertiary care academic medical institution. Patients: A total of 59 men, belonging to three different groups: HIV-positive men with lipodystrophy (n = 21), HIV-positive men without lipodystrophy (n = 20), and age-matched and body mass index-matched HIV-negative controls (n = 18). Methods: Bone density, markers of bone turnover and indices of calcium metabolism were measured in all subjects. Quantitative computed tomography was used both to determine volumetric bone density of the spine and to quantify abdominal visceral fat. Dual energy X-ray absorptiometry was used to determine whole body composition and bone density. Statistical comparisons were performed according to lipodystrophy categorization and protease inhibitor exposure. Results: Men with HIV-associated lipodystrophy had reduced lumbar spine bone density compared with both HIV-infected non-lipodystrophic men (mean +/- SD, 132 +/- 29 versus 154 +/- 30 mg/cm(3); P = 0.021 and HIV-negative controls (mean +/- SD 132 +/- 29 versus 148 +/- 18) mg/cm(3); P = 0.04). Lumbar spine bone density was reduced significantly in HIV lipodystrophy patients independently of protease inhibitor use. In an analysis among all HIV-infected subjects, increased visceral abdominal fat area was associated with decreased lumbar spine bone density (r, -0.47; P = 0.002). The association between visceral fat and bone density remained significant (P = 0.007) after controlling for age, body mass index, lowest body weight, protease inhibitor use, and extremity fat in a multivariate regression model. Markers of bone turnover were not related to bone density or lipodystrophy status. Conclusions: Lumbar spine bone density is reduced in association with increased visceral fat in HIV-infected men with lipodystrophy. Further studies are needed to determine the mechanisms of osteopenia in HIV lipodystrophy and whether increased marrow fat occurs in such patients and affects bone density. (C) 2001 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL457B,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [DK07477, DK 49302, R02 DK 59535] NR 28 TC 82 Z9 85 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 25 PY 2001 VL 15 IS 8 BP 975 EP 982 DI 10.1097/00002030-200105250-00005 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 436HH UT WOS:000168930100004 PM 11399979 ER PT J AU Ganesh, S Agarwala, KL Amano, K Suzuki, T Delgado-Escueta, AV Yamakawa, K AF Ganesh, S Agarwala, KL Amano, K Suzuki, T Delgado-Escueta, AV Yamakawa, K TI Regional and developmental expression of Epm2a gene and its evolutionary conservation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Laforin; Lafora's disease; epilepsy; dual-specificity phosphatase; homologue; expression; conservation; evolution ID PROGRESSIVE MYOCLONUS EPILEPSY; MOUSE; MUTATIONS; LAFORIN; MAP; RAT AB Lafora's disease, an autosomal recessive progressive myoclonus epilepsy, is caused by mutations in the EPM2A gene encoding a dual-specificity phosphatase (DSP) named laforin, Here, we analyzed the developmental and regional expression of murine Epm2a and discussed its evolutionary conservation. A phylogenetic analysis indicated that laforin is evolutionarily distant from other DSPs, Southern zoo blot analysis suggested that conservation of Epm2a gene is limited to mammals. Laforin orthologs (human, mouse, and rat) display more than 94% similarity. All missense mutations known in Lafora disease patients affect conserved residues, suggesting that they may be essential for laforin's function. Epm2a is expressed widely in various organs but not homogeneously in brain, The levels of Epm2a transcripts in mice brains increase postnatally, attaining its highest level in adults. The most intense signal was detected in the cerebellum, hippocampus, cerebral cortex, and the olfactory bulb. Our results suggest that Epm2a is functionally conserved in mammals and is involved in growth and maturation of neural networks. (C) 2001 Academic Press. C1 RIKEN, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 3510198, Japan. Univ Calif Los Angeles, Sch Med, Epilepsy Genet Genom Labs, Comprehens Epilepsy Program, Los Angeles, CA USA. VA GLAHS W Los Angeles Med Ctr, 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 19 TC 29 Z9 32 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 MAY 25 PY 2001 VL 283 IS 5 BP 1046 EP 1053 DI 10.1006/bbrc.2001.4914 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 438LZ UT WOS:000169056400008 PM 11355878 ER PT J AU Adler, B Ashkar, S Cantor, H Weber, GF AF Adler, B Ashkar, S Cantor, H Weber, GF TI Costimulation by extracellular matrix proteins determines the response to TCR ligation SO CELLULAR IMMUNOLOGY LA English DT Article DE T-cell; costimulation; integrin; extracellular matrix protein; vitronectin; osteopontin; apoptosis; interleukin-2d ID T-CELL ACTIVATION; IMMUNODEFICIENCY-VIRUS TYPE-1; IN-VITRO; MEDIATED ACTIVATION; KINASE ACTIVATION; RECEPTOR LIGATION; SIGNALING PATHWAY; GENE-EXPRESSION; TAT PROTEIN; OSTEOPONTIN AB Although ligation of the T-cell antigen receptor (TCR) is central to the responsiveness and antigen specificity of T-cells, it is insufficient to elicit a response. To determine whether the need for costimulation reflects inadequate strength of signal transduction through the TCR or an absolute block of signaling in the absence of a coligand, we studied T-cell activation under serum-free conditions eliminating costimulation by various extracellular matrix proteins which otherwise have an omnipresent and frequently overlooked effect. Engagement of the TCR leads to induction of Fas, but not to measurable IL-2 secretion or apoptosis. Those activation parameters are induced by costimulation through integrin alpha (v)beta (3). Furthermore, T-cell survival or elimination is determined by the type of ligand binding to this coreceptor with vitronectin, fibronectin, and fibrinogen efficiently inducing apoptosis and IL-2 production while osteopontin and entactin mediate IL-2 secretion comparably without causing programmed cell death. Consistent with the cytokine properties of these ligands, differential costimulation depends on their presentation in soluble rather than immobilized form. The determination of elimination versus survival of activated T-cells by coligation of beta (3)-integrins may have bearing on the fundamental postthymic mechanisms that shape the T-cell repertoire. (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. Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Orthoped Surg, Lab Skeletal Disorders & Rehabil, Boston, MA 02115 USA. RP Weber, GF (reprint author), Tufts Univ, Sch Med, New England Med Ctr, 750 Washington St,NEMC 824, Boston, MA 02111 USA. FU NCI NIH HHS [CA76176]; NIAID NIH HHS [AI12184] NR 58 TC 21 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC 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 MAY 25 PY 2001 VL 210 IS 1 BP 30 EP 40 DI 10.1006/cimm.2001.1800 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 463VP UT WOS:000170498200005 PM 11485350 ER PT J AU Sidis, Y Schneyer, AL Sluss, PM Johnson, LN Keutmann, HT AF Sidis, Y Schneyer, AL Sluss, PM Johnson, LN Keutmann, HT TI Follistatin: Essential role for the N-terminal domain in activin binding and neutralization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BONE-MORPHOGENETIC PROTEIN; EARLY XENOPUS EMBRYO; CELL-LINE PA-1; II RECEPTORS; HEPARAN-SULFATE; GROWTH-FACTOR; INHIBIN; AGRIN; SITE; IDENTIFICATION AB Follistatin is recognized to be an important regulator of cellular differentiation and secretion through its potent ability to bind and bioneutralize activin with which it is colocalized in many tissue systems. The 288-residue follistatin molecule is comprised of a 63-residue N-terminal segment followed by three repeating 10-cysteine "follistatin domains" also represented in several extracellular matrix proteins. We have used chemical modifications and mutational analyses to define structural requirements for follistatin bioactivity that previously have not been investigated systematically. Mutant follistatins were stably expressed fi om Chinese hamster ovary cell cultures and assayed for activin binding in a solid-phase competition assay. Biological activities were determined by inhibition of activin-mediated transcriptional activity and by suppression of follicle-stimulating hormone secretion by cultured anterior pituitary cells. Deletion of the entire N-terminal domain, disruption of N-terminal disulfides, and deletion of the first two residues each reduced activin binding to <5 % of expressed wild-type follistatin and abolished the ability of the respective mutants to suppress activin-mediated responses in both bioassay systems. Hence, the three follistatin domains inherently lack the ability to bind or neutralize activin. Activin binding was impaired after oxidation of at least one tryptophan, at position 4, in FS-288, Mutation of Trp to Ala or Asp at either positions 4 or 36 eliminated activin binding and bioactivity, Mutation of a third hydrophobic residue, Phe-52, reduced binding to 20% whereas substitutions for the individual Lys and Arg residues in the N-terminal region were tolerated. These results establish that hydrophobic residues within the N-terminal domain constitute essential activin-binding determinants in the follistatin molecule. The correlation among the effects of mutation on activin binding, activin transcriptional responses, and follicle-stimulating hormone secretion substantiates the concept that, at least in the pituitary, the biological activity of follistatin is attributable to its ability to bind and bioneutralize activin. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Keutmann, HT (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 501, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-53828] NR 50 TC 47 Z9 53 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 MAY 25 PY 2001 VL 276 IS 21 BP 17718 EP 17726 DI 10.1074/jbc.M100736200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500015 PM 11279126 ER PT J AU Yamada, A Takaki, S Hayashi, F Georgopoulos, K Perlmutter, RM Takatsu, K AF Yamada, A Takaki, S Hayashi, F Georgopoulos, K Perlmutter, RM Takatsu, K TI Identification and characterization of a transcriptional regulator for the lck proximal promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTIONAL DISSECTION; THYMOCYTE DEVELOPMENT; BINDING PROTEIN; GENE-EXPRESSION; FACTOR ZBP-89; IKAROS GENE; T-CELLS; FINGER; ENHANCER; RECEPTOR AB The lck gene encodes a protein-tyrosine kinase that plays a key role in signaling mediated through T cell receptor (TCR) and pre-TCR complexes. Transcription of the lck gene is regulated by two independent promoter elements: the proximal and distal promoters. Previous studies employing transgenic mice demonstrated that the sequence between -584 and -240 from the transcription start site in the mouse lck proximal promoter is required for its tissue-specific expression in the thymus, In this study, we demonstrate that a Kruppel-like zinc finger protein, mt beta (BFCOL1, BERF-1, ZBP-89, ZNF148), previously cloned as a protein that binds to the CD3 delta gene enhancer, binds to the -365 to -328 region of the lck proximal promoter. mt beta is ubiquitously expressed in various cell lines and mouse tissues. Overexpressed mt beta is more active in T-lineage cells than B-lineage cells for transactivating an artificial promoter consisting of the mt beta binding site and a TATA box. Activity of the lck proximal promoter was significantly impaired by mutating the mt beta binding site or by reducing mt beta protein expression level by using antisense mRNA. Our results indicate that mt beta activity is regulated in a tissue-specific manner and that mt beta is a critical transactivator for the lck proximal promoter. C1 Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Immunol,Minato Ku, Tokyo 1088639, Japan. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. AMGEN, Thousand Oaks, CA 91320 USA. RP Takaki, S (reprint author), Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Immunol,Minato Ku, Tokyo 1088639, Japan. NR 38 TC 25 Z9 25 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 MAY 25 PY 2001 VL 276 IS 21 BP 18082 EP 18089 DI 10.1074/jbc.M008387200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500063 PM 11278409 ER PT J AU Ito, Y Pandey, P Sathyanarayana, P Ling, P Rana, A Weichselbaum, R Tan, TH Kufe, D Kharbanda, S AF Ito, Y Pandey, P Sathyanarayana, P Ling, P Rana, A Weichselbaum, R Tan, TH Kufe, D Kharbanda, S TI Interaction of hematopoietic progenitor kinase 1 and c-abl tyrosine kinase in response to genotoxic stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-TERMINAL KINASE; ACTIVATED PROTEIN-KINASE; GERMINAL CENTER KINASE; TUMOR-NECROSIS-FACTOR; BETA SIGNAL-TRANSDUCTION; DAMAGE-INDUCED APOPTOSIS; DNA-DAMAGE; IONIZING-RADIATION; 1-BETA-D-ARABINOFURANOSYLCYTOSINE INCORPORATION; CELLULAR-RESPONSE AB The c-Abl protein tyrosine kinase is activated by certain DNA-damaging agents and regulates induction of the stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). The hematopoietic progenitor kinase 1 (HPK1) has also been shown to act upstream to the SAPK/JNK signaling pathway. We report here that exposure of hematopoietic Jurkat T cells to genotoxic agents is associated with activation of HPK1. The results demonstrate that exposure of Jurkat cells to DNA-damaging agents is associated with translocation of active c-Abl from nuclei to cytoplasm and binding of c-Abl to HPK1. Our findings also demonstrate that c-Abl phosphorylates HPK1 in cytoplasm and stimulates HPK1 activity. The functional significance of the c-Abl-HPK1 interaction is supported by the demonstration that this complex regulates SAPK/JNK activation. Overexpression of c-Abl(K-R) inhibits HPK1-induced activation of SAPK/JNK. Conversely, the dominant negative mutant of HPK1 blocks c-Abl-mediated induction of SAPK/JNK. These findings indicate that activation of HPK1 and formation of HPK1/c-Abl complexes are functionally important in the stress response of hematopoietic cells to genotoxic agents. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,Diabet Res Lab, Boston, MA 02114 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. RP Kharbanda, S (reprint author), ILEX Oncol Inc, 20 Overland St, Boston, MA 02215 USA. RI Tan, Tse-Hua/E-3983-2010 OI Tan, Tse-Hua/0000-0003-4969-3170 FU NCI NIH HHS [CA 29431, CA 55241, CA75216]; NIAID NIH HHS [AI8738649] NR 61 TC 12 Z9 15 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 MAY 25 PY 2001 VL 276 IS 21 BP 18130 EP 18138 DI 10.1074/jbc.M007294200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500070 PM 11278340 ER PT J AU Maranda, B Brown, D Bourgoin, S Casanova, JE Vinay, P Ausiello, DA Marshansky, V AF Maranda, B Brown, D Bourgoin, S Casanova, JE Vinay, P Ausiello, DA Marshansky, V TI Intra-endosomal pH-sensitive recruitment of the Arf-nucleotide exchange factor ARNO and Arf6 from cytoplasm to proximal tubule endosomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; GTP-BINDING PROTEIN; RECEPTOR-MEDIATED ENDOCYTOSIS; COP-COATED VESICLES; PLASMA-MEMBRANE; GUANINE-NUCLEOTIDE; GOLGI MEMBRANES; PHOSPHOLIPASE-D; INTRACELLULAR-TRANSPORT; REGULATED EXOCYTOSIS AB Kidney proximal tubule epithelial cells have an extensive apical endocytotic apparatus that is critical for the reabsorption and degradation of proteins that traverse the glomerular filtration barrier and that is also involved in the extensive recycling of functionally important apical plasma membrane transporters. We show here that an Arf-nucleotide exchange factor, ARNO (ADP-ribosylation factor nucleotide site opener) as well as Arf6 and Arf1 small GTPases are located in the kidney proximal tubule receptor-mediated endocytosis pathway, and that ARNO and Arf6 recruitment from cytosol to endosomes is pH-dependent. In proximal tubules in situ, ARNO and Arf6 partially co-localized with the V-ATPase in apical endosomes in proximal tubules, Arf1 was localized both at the apical pole of proximal tubule epithelial cells, but also in the Golgi, By Western blot analysis ARNO, Arf6, and Arf1 were detected both in purified endosomes and in proximal tubule cytosol, A translocation assay showed that ATP-driven endosomal acidification triggered the recruitment of ARNO and Arf6 from proximal tubule cytosol to endosomal membranes. The translocation of both ARNO and Arf6 was reversed by V-type ATPase inhibitors and by uncouplers of endosomal intralumenal pH, and was correlated with the magnitude of intra-endosomal acidification. Our data suggest that V-type ATPase-dependent acidification stimulates the selective recruitment of ARNO and Arf6 to proximal tubule early endosomes, This mechanism may play an important role in the pa-dependent regulation of receptor-mediated endocytosis in proximal tubules in situ. C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. Univ Montreal, GRTM, Montreal, PQ H2L 4M1, Canada. Univ Montreal, CHUM, LC Simard Res Ctr, Lab Renal Biochem, Montreal, PQ H2L 4M1, Canada. Univ Laval, CHUL, Ctr Rech, Ctr Rech Rhumatol & Immunol, Quebec City, PQ G1V 4G2, Canada. Univ Virginia, Hlth Sci Ctr, Dept Cell Biol, Charlottesville, VA 22908 USA. RP Marshansky, V (reprint author), Harvard Univ, Massachusetts Gen Hosp E, Sch Med, Program Membrane Biol, 149 13th St, Boston, MA 02129 USA. FU NIDDK NIH HHS [DK42956, DK38452] NR 67 TC 99 Z9 99 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 MAY 25 PY 2001 VL 276 IS 21 BP 18540 EP 18550 DI 10.1074/jbc.M011577200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 435FJ UT WOS:000168866500123 PM 11278939 ER PT J AU Kaufman, KM Kelly, J Gray-McGuire, C Asundi, N Ya, H Reid, J Baird, T Hutchings, D Bruner, G Scofield, RH Moser, K Harley, JB AF Kaufman, KM Kelly, J Gray-McGuire, C Asundi, N Ya, H Reid, J Baird, T Hutchings, D Bruner, G Scofield, RH Moser, K Harley, JB TI Linkage analysis of angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and systemic lupus erythematosus SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Biological Communications Symposium CY JUN 16-17, 2000 CL MED COLL, AUGUSTA, GEORGIA HO MED COLL DE systemic lupus erythematosus; linkage; angiotensin-converting enzyme (ACE) ID DELETION POLYMORPHISM; SUSCEPTIBILITY GENES; REVISED CRITERIA; ASSOCIATION; CLASSIFICATION; FAMILIES; TRAIT; LOCUS AB Previous studies have suggested an association between systemic lupus erythematosus (SLE) and an insertion/deletion polymorphism in the angiotensin-converting enzyme gene (ACE). This polymorphism consists of a 250-bp insertion/deletion of an alu repeat in the 16th intron of the ACE gene. Individuals homozygous for the deletion have a higher level of circulating enzyme. Due to the important role of this enzyme in regulating the renin-angiotensin and kallikrein-kininogen systems, it is possible that the ACE insertion/deletion may play a role in SLE, which can include vasculitis and vascular changes. Using primers flanking the insertion/deletion site, we have examined the ACE gene in lupus patients and family members using genomic DNA obtained from the Lupus Multiplex Registry and Repository (LMRR). We were unable to detect significant linkage or genetic association between the ACE gene and SLE. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. Univ Minnesota, Sch Med, Div Rheumatol, Oklahoma City, OK USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Kaufman, KM (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAID NIH HHS [AI31584]; NIAMS NIH HHS [AR24717, AR42474, AR42460] NR 21 TC 41 Z9 42 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAY 25 PY 2001 VL 177 IS 1-2 BP 81 EP 85 DI 10.1016/S0303-7207(01)00424-5 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 442EQ UT WOS:000169272600011 PM 11377823 ER PT J AU Daley, J AF Daley, J TI A 58-year-old woman dissatisfied with her care SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-General-Internal Medicine CY MAY 05-06, 2000 CL BOSTON, MASSACHUSETTS SP Soc Gen Internal Med ID PATIENT SATISFACTION; HEALTH-CARE; SELF-MANAGEMENT; HOSPITAL-CARE; MEDICAL-CARE; QUALITY; OUTCOMES; EDUCATION; SERVICE; IMPROVE C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Partners Healthcare Syst, Dept Med, Inst Hlth Policy,Ctr Hlth Syst Design & Evaluat, Boston, MA 02114 USA. RP Daley, J (reprint author), Care of Hartman EE, Beth Israel Deaconess Med Ctr, Div Gen Med, 330 Brookline Ave,LY318, Boston, MA 02215 USA. NR 65 TC 15 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 23 PY 2001 VL 285 IS 20 BP 2629 EP 2635 DI 10.1001/jama.285.20.2629 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 433LY UT WOS:000168761900030 PM 11368737 ER PT J AU Wallhaus, TR Taylor, M DeGrado, TR Russell, DC Stanko, P Nickles, RJ Stone, CK AF Wallhaus, TR Taylor, M DeGrado, TR Russell, DC Stanko, P Nickles, RJ Stone, CK TI Myocardial free fatty acid and glucose use after carvedilol treatment in patients with congestive heart failure SO CIRCULATION LA English DT Article DE fatty acids; glucose; metabolism; heart failure ID LEFT-VENTRICULAR FUNCTION; BETA-ADRENERGIC-BLOCKADE; DOUBLE-BLIND; RAT-HEART; DILATED CARDIOMYOPATHY; OXYGEN-CONSUMPTION; METABOLISM; METOPROLOL; OXIDATION; PLASMA AB Background-Use of beta -adrenoreceptor blockade in the treatment of heart failure has been associated with a reduction in myocardial oxygen consumption and an improvement in myocardial energy efficiency. One potential mechanism for this beneficial effect is a shift in myocardial substrate use from increased free fatty acid (FFA) oxidation to increased glucose oxidation, Methods and Results-We studied the effect of carvedilol therapy on myocardial FFA and glucose use in 9 patients with stable New York Heart Association functional class III ischemic cardiomyopathy (left ventricular ejection fraction less than or equal to 35%) using myocardial positron emission tomography studies and resting echocardiograms before and 3 months after carvedilol treatment. Myocardial uptake of the novel long chain fatty acid metabolic tracer 14(R, S)-[F-18]fluoro-6-thiaheptadecanoic acid ([F-18]-FTHA) was used to determine myocardial FFA use, and [F-18] fluoro-2-deoxy-glucose ([F-18]-FDG) was used to determine myocardial glucose use. After carvedilol treatment, the mean myocardial uptake rate for [F-18]-FTHA decreased (from 20.4+/-8.6 to 9.7+/-2.3 ml . 100 g(-1) . min(-1); P<0.005), mean fatty acid use decreased (from 19.3+/-7.0 to 8.2+/-1.8 moL . 100 g(-1) . min(-1); P<0.005), the mean myocardial uptake rate for [F-18]-FDG was unchanged (from 1.4+/-0.4 to 2.4+/-0.8 mL . 100 g(-1) . min(-1); P=0.14), and mean glucose use was unchanged (from 11.1+/-3.1 to 18.7+/-6.0 moL . 100 g(-1) . min(-1); P=0.12), Serum FFA and glucose concentrations were unchanged, and mean left ventricular ejection fraction improved (from 26+/-2% to 37+/-4%; P<0.05), Conclusions-Carvedilol treatment in patients with heart failure results in a 57% decrease in myocardial FFA use without a significant change in glucose use. These metabolic changes could contribute to the observed improvements in energy efficiency seen in patients with heart failure. C1 William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. Duke Univ, Dept Med Phys, Durham, NC USA. Univ Wisconsin, Dept Med, Madison, WI USA. RP Wallhaus, TR (reprint author), Univ Wisconsin Hosp & Clin, Dept Med, Cardiol Sect, 600 Highland Ave,H6-349, Madison, WI 53792 USA. FU NCRR NIH HHS [RR03186] NR 39 TC 163 Z9 167 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 22 PY 2001 VL 103 IS 20 BP 2441 EP 2446 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 436KC UT WOS:000168934200005 PM 11369683 ER PT J AU Oliveira, J Ezzeddine, MA Segal, AZ Buonanno, FS Chang, Y Ogilvy, CS Rordorf, G Schwamm, LH Koroshetz, WJ McDonald, CT AF Oliveira, J Ezzeddine, MA Segal, AZ Buonanno, FS Chang, Y Ogilvy, CS Rordorf, G Schwamm, LH Koroshetz, WJ McDonald, CT TI Fever in subarachnoid hemorrhage - Relationship to vasospasm and outcome SO NEUROLOGY LA English DT Article ID CEREBRAL VASOSPASM; MODERATE HYPOTHERMIA; MILD HYPOTHERMIA; BODY-TEMPERATURE; BRAIN INJURY; ANEURYSMS; ISCHEMIA; STROKE; RAT; HYPERTHERMIA AB Objective: To investigate the causes of fever in subarachnoid hemorrhage (SAH) and examine its relationship to outcome. Background: Fever adversely affects outcome in stroke. Patients with SAH are at risk for cerebral ischemia due to vasospasm (VSP). In these patients, fever may he both caused by, and potentiate, VSP-mediated brain injury. Methods: The authors prospectively studied patients admitted to a neurologic intensive care unit with nontraumatic SAH, documenting Hunt-Hess grade, Fisher group, Glasgow Coma Score, bacterial culture data, daily transcranial Doppler mean velocities, and maximum daily temperatures. Patients were classified as febrile (temperature above 38.3 degreesC for at least 2 consecutive days) or afebrile (no fever or isolated episodes of temperature above 38.3 degreesC). VSP was verified by either transcranial Doppler or angiographic criteria. Rankin scale scores on discharge were dichotomized into good (0 to 2) or poor (3 to 6) outcomes. Results: Ninety-two consecutive patients were studied. Thirty-eight patients were classified as febrile. No source for infection was found in 10 of 38 (26%) patients. In a multivariate analysis, three variables independently predicted fever occurrence: ventriculostomy (OR, 8.5 [CI, 2.4 to 29.7]), symptomatic VSP (OR, 5.0 [CI, 1.03 to 24.5]), and older age (OR, 1.75 per 10 years [CI, 1.02 to 3.0]). Poor outcome was I elated to fever (OR, 1.4 per each day febrile [CI, 1.1 to 1.88]), older age (OR, 1.64 per 10 years [CI, 1.04 to 2.58]), and intubation (OR, 21.8 [CI, 5.6 to 84.5]). Conclusion: Fever in SAH is associated with vasospasm and poor outcome independently of hemorrhage severity or presence of infection. C1 Massachusetts Gen Hosp, Neurocrit Care Unit, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McDonald, CT (reprint author), Massachusetts Gen Hosp, Neurocrit Care Unit, Dept Neurol, Stroke Serv, 55 Fruit St,Blake 1291, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 FU NINDS NIH HHS [5 P50 NS108288-22, 5 RO1 NS35284, R01-NS28371] NR 33 TC 137 Z9 140 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY 22 PY 2001 VL 56 IS 10 BP 1299 EP 1304 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 433CV UT WOS:000168738500012 PM 11376177 ER PT J AU Payami, H Lee, N Zareparsi, S McNeal, MG Camicioli, R Bird, TD Sexton, G Gancher, S Kaye, J Calhoun, D Swanson, PD Nutt, J AF Payami, H Lee, N Zareparsi, S McNeal, MG Camicioli, R Bird, TD Sexton, G Gancher, S Kaye, J Calhoun, D Swanson, PD Nutt, J TI Parkinson's disease, CYP2D6 polymorphism, and age SO NEUROLOGY LA English DT Article ID HYDROXYLASE GENE POLYMORPHISM; ALPHA-SYNUCLEIN GENE; APOLIPOPROTEIN-E; ALLELIC FREQUENCIES; ALZHEIMERS-DISEASE; HUMAN LONGEVITY; EARLY-ONSET; E GENOTYPE; 2D6 GENE; DEBRISOQUINE AB Objective: PD may be caused by genetic susceptibility to neurotoxins. CYP2D6 is a candidate gene for PD because it regulates drug and toxin metabolism, but association studies have been inconsistent. The aim of this study was to test if the CYP2D6*4 allele (poor metabolizer phenotype) is associated with earlier age at onset. Methods: Five hundred seventy-six patients with PD and 247 subjects without PD were studied using standard diagnostic, genotyping, and statistical techniques. Results: Surprisingly, mean onset age was significantly later in *4-positive patients. Frequency of *4 was significantly higher in late-onset FD than early-onset PD. When early- and late-onset PD were analyzed separately, *4 had no effect on onset age; hence, the association with delayed onset was likely an artifact of an elevated *4 frequency in late-onset PD. Contrary to a common assumption that CYP2D6 frequencies do not change with age, *4 frequency rose significantly with advancing age, both in patients with PD (from 0.16 at mean age of 56.5 years to 0.21 at mean age of 72) and subjects without PD (from 0.09 at mean age of 45.5 years to 0.21 act mean age of 72). *4 Frequencies in patients with early- and late-onset PD, although different from each other, were in agreement with similarly aged subjects without PD, suggesting the elevated *4 frequency in late-onset PD was likely an age effect, unrelated to PD. Conclusion: The CYP2D6*4 allele is not associated with earlier PD onset. *4 May be associated with survival. Inconsistent results from allelic association studies may have been due to an unrecognized age effect. C1 Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Kaiser Permanente, Portland, OR USA. Oregon Hlth Sci Univ, Dept Publ Hlth & Preventat Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. RP Payami, H (reprint author), Oregon Hlth Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,CR131, Portland, OR 97201 USA. OI Kaye, Jeffrey/0000-0002-9971-3478; Camicioli, Richard/0000-0003-2977-8660 FU NCRR NIH HHS [5MO1 RR00334]; NIA NIH HHS [AG0817]; NINDS NIH HHS [R01 NS36960] NR 54 TC 23 Z9 24 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 MAY 22 PY 2001 VL 56 IS 10 BP 1363 EP 1370 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 433CV UT WOS:000168738500024 PM 11376189 ER PT J AU Shimaoka, M Lu, CF Palframan, RT von Andrian, UH McCormack, A Takagi, J Springer, TA AF Shimaoka, M Lu, CF Palframan, RT von Andrian, UH McCormack, A Takagi, J Springer, TA TI Reversibly locking a protein fold in an active conformation with a disulfide bond: Integrin alpha L I domains with high affinity and antagonist activity in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; INTERCELLULAR-ADHESION MOLECULE-1; CRYSTAL-STRUCTURE; CYTOPLASMIC DOMAIN; INSERTED DOMAIN; LIGAND-BINDING; CROSS-LINKING; A-DOMAIN; LFA-1; RECEPTOR AB The integrin alphaL beta2 has three different domains in its headpiece that have been suggested to either bind ligand or to regulate ligand binding. One of these, the inserted or I domain, has a fold similar to that of small G proteins. The I domain of the alphaM and alpha subunits has been crystallized in both open and closed conformations; however, the cut I domain has been crystallized in only the closed conformation. We hypothesized that the cut domain also would have an open conformation, and that this would be the ligand binding conformation. Therefore, we introduced pairs of cysteine residues to form disulfides that would lock the at I domain in either the open or closed conformation. Locking the I domain open resulted in a 9,000-fold increase in affinity to intercellular adhesion molecule-1 (ICAM-1), which was reversed by disulfide reduction. By contrast, the affinity of the locked closed conformer was similar to wild type. Binding completely depended on Mg2+. Orders of affinity were ICAM-1 > ICAM-2 > ICAM-3. The k(on), k(off), and K-D Values for the locked open I domain were within l,5-fold of values previously determined for the alphaL beta2 complex, showing that the I domain is sufficient for full affinity binding to ICAM-1. The locked open I domain antagonized alphaL beta2-dependent adhesion in vitro, lymphocyte homing in vivo, and firm adhesion but not rolling on high endothelial venules. The ability to reversibly lock a protein fold in an active conformation with dramatically increased affinity opens vistas in therapeutics and proteomics. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NCI NIH HHS [R37 CA031798, CA31798, R01 CA031798]; NHLBI NIH HHS [HL54936, HL62524, R01 HL054936] NR 44 TC 165 Z9 169 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2001 VL 98 IS 11 BP 6009 EP 6014 DI 10.1073/pnas.101130498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 435LV UT WOS:000168883700016 PM 11353828 ER PT J AU Santambrogio, L Belyanskaya, SL Fischer, FR Cipriani, B Brosnan, CF Ricciardi-Castagnoli, P Stern, LJ Strominger, JL Riese, R AF Santambrogio, L Belyanskaya, SL Fischer, FR Cipriani, B Brosnan, CF Ricciardi-Castagnoli, P Stern, LJ Strominger, JL Riese, R TI Developmental plasticity of CNS microglia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MHC CLASS-II; COLONY-STIMULATING FACTOR; ANTIGEN-PRESENTING CELLS; IMMATURE DENDRITIC CELLS; CENTRAL-NERVOUS-SYSTEM; MYELIN BASIC-PROTEIN; CATHEPSIN-S; MOUSE-BRAIN; OP/OP MICE; PEPTIDE AB Microglia arise from CD45(+) bone marrow precursors that colonize the fetal brain and play a key role in central nervous system inflammatory conditions. We report that parenchymal microglia are uncommitted myeloid progenitors of immature dendritic cells and macrophages by several criteria, including surface expression of "empty" class II MHC protein and their cysteine protease (cathepsin) profile. Microglia express receptors for stem cell factor and can be skewed toward more dendritic cell or macrophage-like profiles in response to the lineage growth factors granulocyte/macrophage colony-stimulating factor or macrophage colony-stimulating factor. Thus, in contrast to other organs, where terminally differentiated populations of resident dendritic cells and/or macrophages outnumber colonizing precursors, the majority of microglia within the brain remain in an undifferentiated state. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. Univ Milano Bicocca, Dept Biotechnol & Biosci, I-20126 Milan, Italy. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Santambrogio, L (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RI Castagnoli, Paola/E-8288-2010 FU NCI NIH HHS [5R35-CA47554, R01-CA67416]; NIAID NIH HHS [K08-AI01555, N01-AI45198, R01 AI038996, R01-AI38996] NR 33 TC 215 Z9 220 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2001 VL 98 IS 11 BP 6295 EP 6300 DI 10.1073/pnas.111152498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 435LV UT WOS:000168883700065 PM 11371643 ER PT J AU Todo, T Martuza, RL Rabkin, SD Johnson, PA AF Todo, T Martuza, RL Rabkin, SD Johnson, PA TI Oncolytic herpes simplex virus vector with enhanced MHC class I presentation and tumor cell killing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYPE-1 MUTANT G207; ANTIGEN PRESENTATION; INFILTRATING LYMPHOCYTES; ANTITUMOR IMMUNITY; PROTEIN-SYNTHESIS; SAFETY EVALUATION; MALIGNANT GLIOMA; BRAIN-TUMORS; REPLICATION; GENE AB Oncolytic herpes simplex virus type 1 (HSV-1) vectors are promising therapeutic agents for cancer. Their efficacy depends on the extent of both intratumoral viral replication and induction of a host antitumor immune response. To enhance these properties while employing ample safeguards, two conditionally replicating HSV-1 vectors, termed C47 Delta and R47 Delta, have been constructed by deleting the alpha 47 gene and the promoter region of US11 from gamma 34.5deficient HSV-1 vectors, G207 and R3616, respectively. Because the alpha 47 gene product is responsible for inhibiting the transporter associated with antigen presentation (TAP), its absence led to increased MHC class I expression in infected human cells. Moreover, some G47 Delta -infected human melanoma cells exhibited enhanced stimulation of matched antitumor T cell activity. The deletion also places the late US11 gene under control of the immediate-early alpha 47 promoter, which suppresses the reduced growth properties of gamma 34.5-deficient mutants. G47 Delta and R47 Delta showed enhanced viral growth in a variety of cell lines, leading to higher virus yields and enhanced cytopathic effect in tumor cells. G47 Delta was significantly more efficacious in vivo than its parent G207 at inhibiting tumor growth in both immune-competent and immune-deficient animal models. Yet, when inoculated into the brains of HSV-1-sensitive A/J mice at 2 x 10(6) plaque forming units, G47 Delta was as safe as G207. These results suggest that G47 Delta may have enhanced antitumor activity in humans. C1 MediGene Inc, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurosurg Lab,Dept Neurosurg, Charlestown, MA 02129 USA. RP Todo, T (reprint author), Massachusetts Gen Hosp East, Mol Neurosurg Lab, 149 13th St,Box 17, Charlestown, MA 02129 USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NINDS NIH HHS [NS32677, R01 NS032677] NR 39 TC 175 Z9 191 U1 2 U2 14 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 MAY 22 PY 2001 VL 98 IS 11 BP 6396 EP 6401 DI 10.1073/pnas.101136398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 435LV UT WOS:000168883700082 PM 11353831 ER PT J AU Mitsuhashi, T Aoki, Y Eksioglu, YZ Takahashi, T Bhide, PG Reeves, SA Caviness, VS AF Mitsuhashi, T Aoki, Y Eksioglu, YZ Takahashi, T Bhide, PG Reeves, SA Caviness, VS TI Overexpression of p27(Kip1) lengthens the G(1) phase in a mouse model that targets inducible gene expression to central nervous system progenitor cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID G1 PHASE; PROLIFERATIVE EPITHELIUM; CEREBRAL-CORTEX; MICE LACKING; CYCLE; PROGRESSION; SPECIFICATION; HYPERPLASIA; GROWTH; ARREST AB We describe a mouse model in which p27(Kip1) transgene expression is spatially restricted to the central nervous system neuroepithelium and temporally controlled with doxycycline. Transgenespecific transcripts are detectable within 6 h of doxycycline administration, and maximum nonlethal expression is approached within 12 h, After 18-26 h of transgene expression, the G(1) phase of the cell cycle is estimated to increase from 9 to 13 h in the neocortical neuroepithelium, the maximum G(1) phase length attainable in this proliferative population in normal mice. Thus our data establish a direct link between p27(Kip1) and control of G(1) phase length in the mammalian central nervous system and unveil intrinsic mechanisms that constrain the G(1) phase length to a putative physiological maximum despite ongoing p27(Kip1) transgene expression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dev Neurobiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cent Nervous Syst Signaling Lab,Ctr Aging Genet &, Charlestown, MA 02129 USA. RP Reeves, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cent Nervous Syst Signaling Lab,Ctr Aging Genet &, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01 NS035996, NS12005, NS32657, NS35996, R01 NS012005] NR 32 TC 79 Z9 83 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 MAY 22 PY 2001 VL 98 IS 11 BP 6435 EP 6440 DI 10.1073/pnas.111051398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 435LV UT WOS:000168883700089 PM 11371649 ER PT J AU Kumari, S Bhol, KC Rehman, F Foster, CS Ahmed, AR AF Kumari, S Bhol, KC Rehman, F Foster, CS Ahmed, AR TI Interleukin 1 components in cicatricial pemphigoid. Role in intravenous immunoglobulin therapy SO CYTOKINE LA English DT Article DE intravenous immunoglobulin; interleukin 1 alpha; interleukin 1 beta; interleukin 1 receptor antagonist; cicatricial pemphigoid ID INFLAMMATORY BOWEL-DISEASE; IL-1 RECEPTOR ANTAGONIST; NECROSIS-FACTOR-ALPHA; POOLED HUMAN-IGG; IMMUNE GLOBULIN; CYTOKINE PRODUCTION; MONONUCLEAR-CELLS; IN-VIVO; MONOCYTES; EXPRESSION AB Interleukin (IL-)1 is an important mediator of inflammatory responses and plays an important role in the pathogenesis of various autoimmune diseases. Cicatricial pemphigoid (CP) is a multisystem autoimmune inflammatory disease. We have studied the role of IL-1 in its pathogenesis. We have investigated the serum levels of IL-1 components (IL-1 alpha, IL-1 beta, and IL-1Ra), and determined the role of intravenous immunoglobulin (IVIg) therapy in patients,vith CP, Serum levels of IL-1 alpha and beta were significantly higher in untreated patients with active disease compared to levels in patients in prolonged clinical remission and normal human controls (P<0.0001). The serum levels of IL-1Ra were higher in patients in prolonged clinical remission compared to patients with active disease (P=0.002), Hence elevated levels of IL-1 and beta and low levels of IL-1Ra correlate with disease activity, The levels of IL-1 alpha and beta were statistically significantly higher in sera of CP patients with active disease pre-IVIg therapy compared to post-IVIg therapy (P<0.0001). Statistically significantly higher levels of IL-1Ra were present in post-IVIg treatment serum samples when compared to levels in pre-IVIg treatment (P<0.0001). In the in vitro experiments, the levels of IL-1 alpha and beta produced by the peripheral blood mononuclear cells (PBMC) isolated from patients before IVIg therapy were significantly higher when compared to the PBMC isolated from post-IVIg patients (P<0.0001). Significantly higher levels of IL-1Ra were observed in the supernatants of PBMC collected from pre-IVIg patients and cultured with exogenously added IVIg, when compared to the levels of PBMC to which IVIg was not added (P<0.0001). IL-1 may be an important cytokine involved in the pathogenesis of CP, The regulation of IL-1 could be one of the mechanisms, amongst others, by which IVIg may exert its beneficial effect in the treatment of CP. (C) Academic Press. C1 Harvard Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. New England Baptist Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Ahmed, AR (reprint author), Harvard Sch Dent Med, Dept Oral Med & Diagnost Sci, 188 Longwood Ave, Boston, MA 02115 USA. FU NEI NIH HHS [EY08379] NR 44 TC 17 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAY 21 PY 2001 VL 14 IS 4 BP 218 EP 224 DI 10.1006/cyto.2001.0877 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 448AA UT WOS:000169603600004 PM 11448121 ER PT J AU Varghese, S Newsome, JT Rabkin, SD McGeagh, K Mahoney, D Nielsen, P Todo, T Martuza, RL AF Varghese, S Newsome, JT Rabkin, SD McGeagh, K Mahoney, D Nielsen, P Todo, T Martuza, RL TI Preclinical safety evaluation of G207, a replication-competent herpes simplex virus type 1, inoculated intraprostatically in mice and nonhuman primates SO HUMAN GENE THERAPY LA English DT Article ID EXPERIMENTAL BRAIN-TUMORS; PROSTATE-SPECIFIC ANTIGEN; CANCER GENE-THERAPY; ANTITUMOR IMMUNITY; MUTANT G207; ONCOLYTIC THERAPY; MALIGNANT GLIOMAS; VECTOR G207; ADENOVIRUS; MODEL AB C207, a replication-competent herpes simplex virus type 1 (HSV-1) virus, has been previously shown to be effective against human prostate cancer xenografts in mice, This study assesses its safety in the prostate of two animal models known for their sensitivity to HSV-1, BALB/c mice were injected intraprostatically with either HSV-1 G207 or strain F and observed for 5 months. None of the G207-injected animals exhibited any clinical signs of disease or died, However, 50% of strain F-injected mice displayed sluggish, hunched behavior and died by day 13. Histopathologically, the C207-injected prostates were normal whereas strain F-injected prostates showed epithelial flattening, sloughing, and stromal edema. Four Aotus nancymae monkeys were also Injected with G207 intraprostatically and observed short term (up to 21 days) and long term (56 days). Safety was assessed on the basis of clinical observations, viral biodistribution, virus shedding, and histopathology. None of the injected monkeys displayed evidence of clinical disease, shedding of infectious virus, or spread of the virus into other organs. Except for minor histological changes unrelated to the study, no significant abnormalities were observed. These results demonstrate that C207 can be safely inoculated into the prostate and should be considered for human trials for the treatment of prostate cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Neurosurg,Mol Neurosurg Lab, Charlestown, MA 02129 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Div Lab Anim Resources, Pittsburgh, PA 15261 USA. Georgetown Univ Hosp, Dept Urol, Washington, DC 20007 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Martuza, RL (reprint author), Massachusetts Gen Hosp, Dept Surg, Neurosurg Serv, WHT-502,55 Fruit St, Boston, MA 02114 USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 47 TC 46 Z9 48 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY 20 PY 2001 VL 12 IS 8 BP 999 EP 1010 DI 10.1089/104303401750195944 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 437EW UT WOS:000168978900012 PM 11387063 ER PT J AU Moonga, BS Davidson, R Sun, L Adebanjo, OA Moser, J Abedin, M Zaidi, N Huang, CLH Zaidi, M AF Moonga, BS Davidson, R Sun, L Adebanjo, OA Moser, J Abedin, M Zaidi, N Huang, CLH Zaidi, M TI Identification and characterization of a sodium/calcium exchanger, NCX-1, in osteoclasts and its role in bone resorption SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Na+/Ca2+ exchange; osteoclasts; osteoporosis; bone resorption ID RECEPTOR ACTIVATION; INTRACELLULAR PH; RAT OSTEOCLASTS; CYTOPLASMIC PH; NEONATAL RAT; CALCIUM; CALCITONIN; TRANSPORT; MECHANISM; PUMPS AB We provide the first demonstration for a Na+/Ca2+ exchanger, NCX-1, in the osteoclast. We speculate that by using Na+ exchange, NCX-1 couples H+ extrusion with Ca2+ fluxes during bone resorption. Microspectrofluorimetry of fura-a-loaded osteoclasts revealed a rapid and sustained, but reversible, cytosolic Ca2+ elevation upon Na+ withdrawal. This elevation was abolished by the cytosolic introduction (by gentle permeabilization) of a highly specific Na+/Ca2+ exchange inhibitor peptide, XIP, but not its inactive analogue, sXIP. Confocal microscopy revealed intense plasma membrane immunofluorescence with an isoform-specific monoclonal anti-NCX-1 antibody applied to gently permeabilized osteoclasts. Electrophysiological studies using excised outside-in membrane patches showed a low-conductance, Na+-selective, dichlorobenzamil-sensitive, amiloride-insensitive channel that we tentatively assigned as being an NCX. Finally, to examine for physiological relevance, an osteoclast resorption (pit) assay was performed. There was a dramatic reduction of bone resorption following NCX-1 inhibition by dichlorobenzamil and XIP (but not with S-XIP). Together, the results suggest that a functional NCX, likely NCX-1, is involved in the regulation of osteoclast cytosolic Ca2+ and bone resorption. (C) 2001 Academic Press. C1 Mt Sinai Sch Med, Mt Sinai Bone Program, Dept Med, New York, NY 10029 USA. Mt Sinai Sch Med, Mt Sinai Bone Program, Dept Geriatr, New York, NY 10029 USA. Bronx Vet Affairs Geriatr Res Educ & Clin Ctr, New York, NY USA. NYU, David Kriser Sch Dent, New York, NY USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. Univ Cambridge, Physiol Lab, Cambridge CB2 3EG, England. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Zaidi, M (reprint author), Mt Sinai Sch Med, Mt Sinai Bone Program, Dept Med, POB 1055,1 Gustav Levy Pl, New York, NY 10029 USA. RI Huang, Christopher/A-6248-2008 FU NIA NIH HHS [R01-AG14917-05] NR 28 TC 15 Z9 16 U1 0 U2 2 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 MAY 18 PY 2001 VL 283 IS 4 BP 770 EP 775 DI 10.1006/bbrc.2001.4870 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 436GP UT WOS:000168928400009 PM 11350050 ER PT J AU Schuyler, SC Pellman, D AF Schuyler, SC Pellman, D TI Microtubule "plus-end-tracking proteins": The end is just the beginning SO CELL LA English DT Review ID YEAST; CLIP-170; DYNAMICS C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Schuyler, SC (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 20 TC 281 Z9 291 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 18 PY 2001 VL 105 IS 4 BP 421 EP 424 DI 10.1016/S0092-8674(01)00364-6 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 434XG UT WOS:000168840700002 PM 11371339 ER PT J AU Hamazaki, T Iiboshi, Y Oka, M Papst, PJ Meacham, AM Zon, LI Terada, N AF Hamazaki, T Iiboshi, Y Oka, M Papst, PJ Meacham, AM Zon, LI Terada, N TI Hepatic maturation in differentiating embryonic stem cells in vitro SO FEBS LETTERS LA English DT Article DE embryonic stem cell; hepatocyte; in vitro differentiation; SEK1; tyrosine aminotransferase ID ACTIVATED PROTEIN-KINASE; VISCERAL YOLK-SAC; LIVER DEVELOPMENT; HUMAN BLASTOCYSTS; GENE-EXPRESSION; MOUSE EMBRYOS; MICE LACKING; ONCOSTATIN-M; FETAL-RAT; IN-VITRO AB We investigated the potential of mouse embryonic stem (ES) cells to differentiate into hepatocytes in vitro. Differentiating ES cells expressed endodermal-specific genes, such as alpha -fetoprotein, transthyretin, a l-anti-trypsin and albumin, when cultured without additional growth factors and late differential markers of hepatic development, such as tyrosine aminotransferase (TAT) and glucose-6-phosphatase (G6P). when cultured in the presence of growth factors critical for late embryonic liver development. Further, induction of TAT and G6P expression was induced regardless of expression of the functional SEK1 gene, which is thought to provide a survival signal for hepatocytes during an early stage of liver morphogenesis, The data indicate that the in vitro ES differentiation system has a potential to generate mature hepatocytes. The system has also been found useful in analyzing the role of growth factors and intracellular signaling molecules in hepatic development. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Univ Florida, Coll Med, Dept Pathol, Gainesville, FL 32610 USA. Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Florida, Coll Med, Program Stem Cell Biol, Shands Canc Ctr, Gainesville, FL 32610 USA. RP Terada, N (reprint author), Univ Florida, Coll Med, Dept Pathol, POB 100275, Gainesville, FL 32610 USA. FU NIDDK NIH HHS [DK-59699] NR 40 TC 297 Z9 335 U1 2 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 18 PY 2001 VL 497 IS 1 BP 15 EP 19 DI 10.1016/S0014-5793(01)02423-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 435NV UT WOS:000168888300003 PM 11376655 ER PT J AU Wang, WH Lee, SB Palmer, R Ellisen, LW Haber, DA AF Wang, WH Lee, SB Palmer, R Ellisen, LW Haber, DA TI A functional interaction with CBP contributes to transcriptional activation by the Wilms tumor suppressor WT1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR-PROTEIN CBP; FACTOR-A-CHAIN; GENE-PRODUCT; KIDNEY-CELLS; BINDING; P53; REPRESSION; APOPTOSIS; RECEPTOR; E1A AB The Wilms tumor gene WT1 encodes a zinc finger transcription factor that is required for normal kidney development. WT1 was identified as a transcriptional repressor, based on its suppression of promoter reporters, but analysis of native transcripts using high density microarrays has uncovered transcriptional activation, rather than repression, of potential target genes. We report here that WT1 binds to the transcriptional coactivator CBP, leading to synergistic activation of a physiologically relevant promoter. The physical interaction between WT1 and CBP is evident in vitro and in vivo, and the two proteins are co-immunoprecipitated from embryonic rat kidney cells. The WT1-CBP association requires the first two zinc fingers of WT1 and the adenovirus 5 E1A-binding domain of CBP. Overexpression of this domain of CBP is sufficient to inhibit WT1-mediated transcriptional activation of a promoter reporter, as is co-transfection of Elk Retrovirally driven expression of either the CBP fragment or of E1A in human hematopoietic cells suppresses the induction by WT1 of its endogenous target gene, p21(Cip1). These observations support a model of WT1 as a transcriptional activator of genes required for cellular differentiation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY 7,Bldg 149,13 St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA58595] NR 49 TC 31 Z9 31 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 MAY 18 PY 2001 VL 276 IS 20 BP 16810 EP 16816 DI 10.1074/jbc.M009687200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432ZG UT WOS:000168730400030 PM 11278547 ER PT J AU Kumar, S Bharti, A Mishra, NC Raina, D Kharbanda, S Saxena, S Kufe, D AF Kumar, S Bharti, A Mishra, NC Raina, D Kharbanda, S Saxena, S Kufe, D TI Targeting of the c-Ab1 tyrosine kinase to mitochondria in the necrotic cell death response to oxidative stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVATED PROTEIN-KINASE; C-ABL; DNA-DAMAGE; APOPTOTIC RESPONSE; GENERATION; NUCLEAR; P73 AB The ubiquitously expressed c-Abl tyrosine kinase is activated in the response of cells to genotoxic and oxidative stress. The present study demonstrates that reactive oxygen species (ROS) induce targeting of c-Abl to mitochondria. We show that ROS-induced localization of c-Abl to mitochondria is dependent on activation of protein kinase C (PKC)S and the c-Abl kinase function. Targeting of c-Abl to mitochondria is associated with ROS-induced loss of mitochondrial transmembrane potential. The results also demonstrate that c-Abl is necessary for ROS-induced depletion of ATP and the activation of a necrosis-like cell death. These findings indicate that the c-Abl kinase targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Lovelace Resp Res Inst, Albuquerque, NM 87115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42802] NR 28 TC 81 Z9 89 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 MAY 18 PY 2001 VL 276 IS 20 BP 17281 EP 17285 DI 10.1074/jbc.M101414200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432ZG UT WOS:000168730400091 PM 11350980 ER PT J AU Mukhin, YV Vlasova, T Jaffa, AA Collinsworth, G Bell, JL Tholanikunnel, BG Pettus, T Fizgibbon, W Ploth, DW Raymond, JR Garnovskaya, MN AF Mukhin, YV Vlasova, T Jaffa, AA Collinsworth, G Bell, JL Tholanikunnel, BG Pettus, T Fizgibbon, W Ploth, DW Raymond, JR Garnovskaya, MN TI Bradykinin B-2 receptors activate Na+/H+ exchange in mIMCD-3 cells via Janus kinase 2 aHld Ca2+/calmodulin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-STIMULATED PHOSPHORYLATION; EPIDERMAL-GROWTH-FACTOR; COLLECTING DUCT CELLS; PROTEIN-KINASE; TYROSINE RESIDUES; 5-HT1A RECEPTOR; ISOFORM-1 NHE1; CALMODULIN; SITES; IDENTIFICATION AB We used a cultured murine cell model of the inner medullary collecting duct (mIMCD-3 cells) to examine the regulation of the ubiquitous sodium-proton exchanger, Na+/H+ exchanger isoform 1 (NHE-1), by a prototypical G protein-coupled receptor, the bradykinin B, receptor. Bradykinin rapidly activates NHE-1 in a concentration-dependent manner as assessed by proton microphysiometry of quiescent cells and by 2'-7'-bis[2-carboxymethyl]-5(6)-carboxyfluorescein fluorescence measuring the accelerated rate of pH, recovery from an imposed acid load. The activation of NHE-1 is blocked by inhibitors of the bradykinin B, receptor, phospholipase C, Ca2+/calmodulin (CaM), and Janus kinase 2 (Jak2), but not by pertussis toxin or by inhibitors of protein kinase C and phosphatidylinositol 3'-kinase, Immunoprecipitation studies showed that bradykinin stimulates the assembly of a signal transduction complex that includes CaM, Jak2, and NHE-1, CaM appears to be a direct substrate for phosphorylation by Jak2 as measured by an in vitro kinase assay. We propose that Jak2 is a new indirect regulator of NHE-1 activity, which modulates the activity of NHE-1 by increasing the tyrosine phosphorylation of Ca2+ and most likely by increasing the binding of CaM to NHE-1. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Div Endocrinol, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. RP Garnovskaya, MN (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Rm 829 CSB,171 Ashley Ave, Charleston, SC 29425 USA. FU NCRR NIH HHS [S10 RR13005]; NIDDK NIH HHS [DK52448, K01-DK02694] NR 51 TC 25 Z9 25 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 MAY 18 PY 2001 VL 276 IS 20 BP 17339 EP 17346 DI 10.1074/jbc.M010834200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432ZG UT WOS:000168730400099 PM 11278760 ER PT J AU Fukumoto, S Hsieh, CM Maemura, K Layne, RD Yet, SF Lee, KH Matsui, T Rosenzweig, A Taylor, WG Rubin, JS Perrella, MA Lee, ME AF Fukumoto, S Hsieh, CM Maemura, K Layne, RD Yet, SF Lee, KH Matsui, T Rosenzweig, A Taylor, WG Rubin, JS Perrella, MA Lee, ME TI Akt participation in the Wnt signaling pathway through dishevelled SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3-BETA; BETA-CATENIN STABILITY; PROTEIN-KINASE-B; PC12 CELLS; CYCLIN D1; GENE; ACTIVATION; EXPRESSION; WINGLESS; AXIN AB Inactivation of glycogen synthase kinase 3 beta (GSKS beta) and the resulting stabilization of free beta -catenin are critical steps in the activation of Wnt target genes. While Akt regulates GSK3 alpha/beta in the phosphatidylinositide 3-OH kinase signaling pathway, its role in Wnt signaling is unknown. Here we report that expression of Wnt or Dishevelled (Dvl) increased Akt activity. Activated Akt bound to the Axrin-GSK3 beta complex in the presence of Dvl, phosphorylated GSK3 beta and increased free beta -catenin levels. Furthermore, in Wnt-overexpressing PC12 cells, dominant-negative Akt decreased free beta -catenin and derepressed nerve growth factor-induced differentiation. Therefore, Akt acts in association with Dvl as an important regulator of the Wnt signaling pathway. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Perrella, MA (reprint author), Brigham & Womens Hosp, Dept Med, Div Pulm, 75 Francis St,Thorn Bldg,Rm TH1133, Boston, MA 02115 USA. RI Yet, Shaw-Fang/B-1067-2010; OI Yet, Shaw-Fang/0000-0001-9097-3962 FU NHLBI NIH HHS [HL57977, HL60788]; NIGMS NIH HHS [GM53249] NR 35 TC 213 Z9 220 U1 0 U2 8 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 MAY 18 PY 2001 VL 276 IS 20 BP 17479 EP 17483 DI 10.1074/jbc.C000880200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 432ZG UT WOS:000168730400119 PM 11278246 ER PT J AU Wen, Y Ibaraki, N Reddy, VN Sachs, G AF Wen, Y Ibaraki, N Reddy, VN Sachs, G TI Functional analysis of the promoter and chromosomal localization for human LEP503, a novel lens epithelium gene SO GENE LA English DT Article DE cDNA cloning; transcription factor binding site; inherited cataract; gene expression ID CELL MESSENGER-RNA; RAT LENS; TRANSCRIPTION FACTORS; CATARACT FORMATION; EXPRESSION; DIFFERENTIATION; CLONING; PROTEIN AB LEP503 is a novel gene product isolated from lens epithelial cells by a subtractive cDNA cloning strategy. It is highly conserved in different vertebrate species and developmentally regulated in postnatal rat lens, suggesting that LEP503 may be an important lens epithelium gene involved in the processes of lens epithelial cell differentiation. The expression of LEP503 is highly restricted to lens epithelial cells in vivo. To investigate the molecular mechanisms regulating the promoter of the human LEP503, we cloned and characterized the promoter of the human LEP503 gene, The transcription start site was localized to a nucleotide C 22 base pairs (bp) 5' of the initiation methionine codon. By reporter gene transfection experiments, we found that similar to2.5-kb of LEP503 5'-flanking sequence directed high level luciferase activity in human lens epithelial cells; further deletion analysis revealed positive regulatory element between bp -401 and +22, Mutation analysis in each of the seven potential binding sites for transcription factors within the region between -401 and +22 showed that the AP-1 element at -131 and the Spl element at -48 are the most important sites for the tissue-specific expression of LEP503. Consistent with lens epithelial cell-restricted expression of LEP503 mRNA, we found that the similar to2.5-kb 5'-flanking sequence directed high-level promoter activity in lens epithelial cells but not in other cell types. Understanding the LEP503 promoter will allow us to investigate lens epithelial cell-specific gene regulation and to uncover methods for targeting gene delivery specifically to lens epithelial cells. The LEP503 gene is mapped to human chromosome 1q22, the same location to which zonular pulverulent cataract was previously mapped. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Physiol, Membrane Biol Lab, Los Angeles, CA 90073 USA. Chiba Hokusoh Hosp, Dept Ophthalmol, Nippon Med Sch, Chiba 2701694, Japan. Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI USA. RP Wen, Y (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. FU NEI NIH HHS [EY07003, EY00484]; NIDDK NIH HHS [DK41301, DK46917, DK53462, DK58333] NR 30 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 16 PY 2001 VL 269 IS 1-2 BP 61 EP 71 DI 10.1016/S0378-1119(01)00439-5 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 440AP UT WOS:000169151100007 PM 11376938 ER PT J AU Gillman, MW Rifas-Shiman, SL Camargo, CA Berkey, CS Frazier, AL Rockett, HRH Field, AE Colditz, GA AF Gillman, MW Rifas-Shiman, SL Camargo, CA Berkey, CS Frazier, AL Rockett, HRH Field, AE Colditz, GA TI Risk of overweight among adolescents who were breastfed as infants SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEYS; CHILDHOOD OBESITY; FOLLOW-UP; ENDOCRINE RESPONSES; FEEDING PRACTICES; YOUNG ADULTHOOD; NATIONAL-HEALTH; CHILDREN; GROWTH AB Context Overweight during adolescence predicts short- and long-term morbidity as well as obesity in adulthood. The prevalence of overweight among adolescents is high and continues to increase. Physiological and behavioral mechanisms and preliminary epidemiologic data suggest that breastfeeding could lower the risk of subsequent obesity in adolescence. Objective To examine the extent to which overweight status among adolescents is associated with the type of infant feeding (breast milk vs infant formula) and duration of breastfeeding. Design, Setting, and Subjects Survey of 8186 girls and 7155 boys, aged 9 to 14 years, who are participants in the Growing Up Today Study, a nationwide cohort study of diet, activity, and growth. In the fall of 1996 we mailed a questionnaire to each of the subjects, and in the spring of 1997, we mailed a supplemental questionnaire to their mothers, who are participants in the Nurses' Health Study II. Main Outcome Measure Overweight status defined as body mass index exceeding the 95th percentile for age and sex from US national data. Results In the first 6 months of life, 9553 subjects (62%) were only or mostly fed breast milk, and 4744 (31%) were only or mostly fed infant formula. A total of 7186 subjects (48%) were breastfed for at least 7 months while 4613 (31%) were breastfed for 3 months or less. At ages 9 to 14 years, 404 girls (5%) and 635 boys (9%) were overweight. Among subjects who had been only or mostly fed breast milk, compared with those only or mostly fed formula, the odds ratio (OR) for being overweight was 0.78 (95% confidence interval [CI], 0.66-0.91), after adjustment for age, sex, sexual maturity, energy intake, time watching television, physical activity, mother's body mass index, and other variables reflecting social, economic, and lifestyle factors. Compared with subjects who had been breastfed for 3 months or less, those who had been breastfed for at least 7 months had an adjusted OR for being overweight of 0.80 (95% CI, 0.67-0.96). Timing of introduction of solid foods, infant formula, or cow's milk was not related to risk of being overweight, Conclusion Infants who were fed breast milk more than infant formula, or who were breastfed for longer periods, had a lower risk of being overweight during older childhood and adolescence. C1 Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Dept Amulatory Care & Prevent, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA. RP Gillman, MW (reprint author), Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Dept Amulatory Care & Prevent, 126 Brookline Ave,Suite 200, Boston, MA 02215 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 50385]; NIDDK NIH HHS [DK 46834] NR 52 TC 391 Z9 414 U1 4 U2 30 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 MAY 16 PY 2001 VL 285 IS 19 BP 2461 EP 2467 DI 10.1001/jama.285.19.2461 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 429ZC UT WOS:000168547600027 PM 11368698 ER PT J AU Kawamura, A Abrell, LM Maggiali, F Berova, N Nakanishi, K Labutti, J Magil, S Haupert, GT Hamlyn, JM AF Kawamura, A Abrell, LM Maggiali, F Berova, N Nakanishi, K Labutti, J Magil, S Haupert, GT Hamlyn, JM TI Biological implication of conformational flexibility in ouabain: Observations with two ouabain phosphate isomers SO BIOCHEMISTRY LA English DT Article ID DEPENDENT ADENOSINE-TRIPHOSPHATASE; CARDIAC GLYCOSIDE COMPLEXES; ADRENOCORTICAL-CELLS; CARDIOTONIC STEROIDS; ENDOGENOUS OUABAIN; RATE CONSTANTS; MDCK; INHIBITION; ATPASE; STATE AB Ouabain is a highly polar acid unusually potent sodium pump inhibitor that possesses uncommon conformational flexibility in its steroid A-ring moiety. The biological significance of ring flection in the cardiotonic steroids has not been described. Accordingly, we prepared ouabain 1,5,19- and 1,11,19-phosphates. The former stabilizes the steroid A-ring chair conformation and the latter locks the A-ring in the half-boat conformation and decreases flection of the ABC-ring moiety. Using a dog kidney cell line (MDCK) in a pH microphysiometer (Cytosensor), ouabain and its 1,5,19-phosphate at 10(-5) M reduced the rate of extracellular acidification by 15-20%. During inhibitor washout, the rate of recovery from the 1,5,19-phosphate analogue was similar to3 times faster than ouabain. The 1,11,19-phosphate at 10(-4) M elicited a weak (similar to7%) response, and the effects reversed similar to 44-fold faster than ouabain. Studies with purified Na+,K+-ATPase showed that ouabain and its 1,5,19-phosphate analogue were of similar efficacy (EC50 = 1.1 and 5.2 x 10(-7) M, respectively) and > 100-fold more potent than the 1,11,19-phosphate analogue. Studies of the binding kinetics showed that the 1,5,19-phosphate analogue bound 3-fold and dissociated 16-fold faster from the purified Na+,K+-ATPase than ouabain, Both analogues were competitive inhibitors of H-3-ouabain binding. Taken together, these results suggest that the marked conformational flexibility of the A-ring in ouabain ordinarily slows the initial binding of this steroid to the sodium pump. However, once ouabain is bound, flection of the steroidal A- and BC-rings is critical for the maintenance of high affinity binding. Our results indicate that the ouabain-binding site is comprised of structurally mobile elements and highlight the roles that synchronization between receptor and ligand dynamics play as determinants of biological activity in this system. C1 Columbia Univ, Dept Chem, New York, NY 10027 USA. BION Inc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv,Renal Unit, Charlestown, MA 02129 USA. Univ Maryland, Dept Physiol, Baltimore, MD 21201 USA. RP Nakanishi, K (reprint author), Columbia Univ, Dept Chem, New York, NY 10027 USA. OI Abrell, Leif/0000-0003-2490-1180 FU NHLBI NIH HHS [HL52282]; NIAID NIH HHS [AI10187]; NIDDK NIH HHS [DK 53492] NR 25 TC 24 Z9 24 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 15 PY 2001 VL 40 IS 19 BP 5835 EP 5844 DI 10.1021/bi0101751 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 431MV UT WOS:000168635900028 PM 11341849 ER PT J AU Planas-Silva, MD Shang, YF Donaher, JL Brown, M Weinberg, RA AF Planas-Silva, MD Shang, YF Donaher, JL Brown, M Weinberg, RA TI AIB1 enhances estrogen-dependent induction of cyclin D1 expression SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER CELLS; STEROID-RECEPTOR COACTIVATOR-1; RETINOBLASTOMA PROTEIN; PROGESTERONE-RECEPTOR; E-CDK2 ACTIVATION; GENE-EXPRESSION; IN-SITU; GROWTH; MCF-7; TRANSCRIPTION AB AIB1 was isolated as a gene amplified in breast cancer and encodes a protein that acts as a steroid receptor coactivator, The role of steroid receptor coactivators such as AIB1 in breast cancer development is not clear. It is possible that AIB1 cooperates with estrogen receptor a in regulating estrogen-dependent cell proliferation. Ectopic expression of the estrogen receptor a in different cell lines does not confer estrogen-induced proliferation, This inability of the estrogen receptor to drive proliferation has been recently correlated with a lack of estrogen-dependent cyclin D1 expression in cells engineered to express the estrogen receptor. In this study, we evaluated whether high levels of AIB1 enable the estrogen receptor to direct the transcription of cyclin D1, We show here that AIB1 and other steroid receptor coactivators can enhance the functional interaction of the estrogen receptor with the cyclin D1 promoter. Increases of AIB1 levels in breast cancer cells by amplification and/or overexpression may represent one way to confer estrogen-dependent mitogenic stimulation to breast cancer cells. C1 MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Weinberg, RA (reprint author), MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [P01 CA 80111] NR 25 TC 93 Z9 95 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 MAY 15 PY 2001 VL 61 IS 10 BP 3858 EP 3862 PG 5 WC Oncology SC Oncology GA 436HC UT WOS:000168929600003 PM 11358796 ER PT J AU Akewanlop, C Watanabe, M Singh, B Walker, M Kufe, DW Hayes, DF AF Akewanlop, C Watanabe, M Singh, B Walker, M Kufe, DW Hayes, DF TI Phagocytosis of breast cancer cells mediated by anti-MUC-1 monoclonal antibody, DF3, and its bispecific antibody SO CANCER RESEARCH LA English DT Article ID DEPENDENT CELLULAR CYTOTOXICITY; FC-GAMMA-RI; HUMAN-MONOCYTES; TUMOR-CELLS; EXPRESSION; REACTIVITY; INDUCTION; PROTEIN; ANTIGEN; THERAPY AB Human epithelial mucin, MUC-1, is commonly expressed in adenocarcinoma including 80% of breast cancers, erbB-2 is overexpressed in similar to 30% of breast cancers. Expression of MUC-1 and erbB-2 may be partially overlapping but discoordinate, Therefore, combined use of antibodies directed against these two antigens might increase the number of patients who benefit from immunotherapy, Monoclonal antibody (MAb) DF3 recognizes the MUC-1 tandem repeat, We investigated phagocytosis and cytolysis of cultured human breast cancer cells by monocyte-derived macrophages mediated by MAb DF3 and its bispecific antibody (BsAb) DF3xH22 with the second epitope directed against the Fe component of phagocytic cells. Purified monocytes from healthy donors were cultured with granulocyte macrophage colony-stimulating factor with or without IFN-gamma, antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent cellular cytotoxicity (ADCC) assays were performed with these macrophages and MUC-1-expressing target cells (ZR75-1) in the presence of MAb DF3 and BsAb DF3xH22. ADCP was measured by two-color fluorescence flow cytometry using PKH2 (green fluorescent dye) and R-phytoerythrin (RPE) (red)-conjugated MAb against human CD14 and CD11b and was confirmed by confocal microscopy, ADCC was measured by Cr-51 release assay. Immunohistochemical staining studies of MUG-I and erbB-2 were performed on 67 primary breast cancer tissues. Expression of MUG-I and erbB-2 was partially overlapping but discoordinate in 67 consecutive breast cancers. Both MAb DF3 and BsAb DF3xH22 mediated ADCP, However, ADCP mediated by MAb DF3 was greater than that mediated by BsAb DF3xH22. ADCC as detected by Cr-51 release was not seen with either antibody. The addition of IFN-gamma to monocyte-derived macrophage cultures inhibited ADCP compared to granulocyte macrophage colony-stimulating factor alone. Given the partially overlapping but discoordinate expression of MUG-I and erbB-2 in breast cancer, therapy directed toward both antigens should be considered. MAb DF3 and the BsAb DF3xH22, can effectively mediate phagocytosis of MUG-I-expressing target cells. Further investigations are needed to determine whether this antibody-induced phagocytosis results in long-term specific T-cell activation against MUC-1. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Breast Canc Program, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pathol, Washington, DC 20007 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hayes, DF (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Breast Canc Program, Res Bldg Room E-504,3970 Reservoir Rd,NW, Washington, DC 20007 USA. FU NCI NIH HHS [CA64057, P30-CA-51008] NR 24 TC 31 Z9 36 U1 0 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 MAY 15 PY 2001 VL 61 IS 10 BP 4061 EP 4065 PG 5 WC Oncology SC Oncology GA 436HC UT WOS:000168929600033 PM 11358826 ER PT J AU Xu, GW Nutt, CL Zlatescu, MC Keeney, M Chin-Yee, I Cairncross, JG AF Xu, GW Nutt, CL Zlatescu, MC Keeney, M Chin-Yee, I Cairncross, JG TI Inactivation of p53 sensitizes U87MG glioma cells to 1,3-bis(2-chloroethy1)-1-nitrosourea SO CANCER RESEARCH LA English DT Article ID ANTICANCER AGENTS; GLIOBLASTOMA CELLS; MALIGNANT GLIOMA; CYCLE ARREST; DNA-DAMAGE; S-PHASE; GENE; EXPRESSION; CISPLATIN; CANCER AB We examined the effect of p53 inactivation on the response of U87MG glioma cells to 1,3-bis(2-chloroethy)-1-nitrosourea (BCNU). These studies were motivated by three observations: (a) some human astrocytomas are sensitive to BCNU and some are resistant; (b) chemosensitive astrocytomas are more likely to be found in young adults whose tumors are more likely to harbor a p53 mutation; and (c) mouse astrocytes lacking the p53 gene are more sensitive to BCNU than wild-type cells. Here, we observed that p53 inactivation by transfection with pCMV-E6 sensitized U87MG cells to BCNU. Compared with control U87MG-neo cells with intact p53 Function, the clonogenic survival of U87MG-E6 cells exposed to BCNU was reduced significantly. In U87MG-E6 cells, sensitization to BCNU was associated with failure of p21(WAF1) induction, transient cell cycle arrest in S phase, accumulation of polyploid cells, and significant cell death. In contrast, resistance to BCNU in U87MG-neo cells was associated with upregulation of p53, prolonged induction of p21(WAF1), sustained cell cycle arrest in S phase, and enhancement of DNA repair. U87MG cells with disrupted p53 function were less able to repair BCNU-induced DNA damage and survive this chemotherapeutic insult. The question arises of,whether p53 dysfunction might be a chemosensitizing genetic alteration in human astrocytic gliomas. C1 London Reg Canc Ctr, Canc Res Lab, London, ON N6A 4L6, Canada. Univ Western Ontario, Dept Oncol, London, ON N6A 3K7, Canada. Univ Western Ontario, Dept Med, London, ON N6A 3K7, Canada. Univ Western Ontario, Neurosci Program, London, ON N6A 3K7, Canada. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Cairncross, JG (reprint author), London Reg Canc Ctr, Canc Res Lab, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. RI Nutt, Catherine/K-8794-2012 NR 25 TC 28 Z9 30 U1 0 U2 0 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 MAY 15 PY 2001 VL 61 IS 10 BP 4155 EP 4159 PG 5 WC Oncology SC Oncology GA 436HC UT WOS:000168929600046 PM 11358839 ER PT J AU Wang, VW Bell, DA Berkowitz, RS Mok, SC AF Wang, VW Bell, DA Berkowitz, RS Mok, SC TI Whole genome amplification and high-throughput allelotyping identified five distinct deletion regions on chromosomes 5 and 6 in microdissected early-stage ovarian tumors SO CANCER RESEARCH LA English DT Article ID MOLECULAR-GENETIC CHANGES; ALLELIC LOSS; SINGLE-CELL; LOW-GRADE; CANCER; HETEROZYGOSITY; CARCINOMAS; DNA; PCR; MUTATIONS AB Investigation of genetic changes in tumors by loss of heterozygosity is a powerful technique for identifying chromosomal regions that may contain tumor suppressor genes. In this study, we determined allelic loss on chromosomes 5 and 6 in 29 primary early-stage epithelial ovarian carcinomas including 3 microscopically identified adenocarcinomas using a high-throughput PCR-based method combined with laser capture microdissection and whole genome amplification techniques. Twenty microsatellite markers spanning chromosomes 5 and 6 at an average distance of 20 cM were examined. High frequencies of loss on chromosome 5 were identified at loci D5S428 (48 %), D5S424 (32 %), and D5S630 (32 %). Our study also showed that chromosome 6 exhibited high frequencies of loss of heterozygosity at loci D6S1574 (46 %), D6S287 (42 %), D6S441 (45 %), D6S264 (60 %), and D6S281 (35 %). These results suggest that multiple tumor suppressor genes are located on five distinct regions on chromosomes 5 and 6, i.e., 5p15.2, 5q13-21, 6p24-25, 6q21-23, and 6q25.1-27, and may be involved in the early development of ovarian carcinomas. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Harvard Canc Ctr, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Harvard Canc Ctr, Div Gynecol Oncol,Lab Gynecol Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Harvard Canc Ctr,Dept Pathol, Boston, MA 02114 USA. RP Mok, SC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Harvard Canc Ctr, Dept Obstet Gynecol & Reprod Biol, 221 Longwood Ave,BLI-449, Boston, MA 02115 USA. NR 34 TC 38 Z9 44 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 MAY 15 PY 2001 VL 61 IS 10 BP 4169 EP 4174 PG 6 WC Oncology SC Oncology GA 436HC UT WOS:000168929600048 PM 11358841 ER PT J AU Genbacev, O Krtolica, A Kaelin, W Fisher, SJ AF Genbacev, O Krtolica, A Kaelin, W Fisher, SJ TI Human cytotrophoblast expression of the von Hippel-Lindau protein is downregulated during uterine invasion in situ and upregulated by hypoxia in vitro SO DEVELOPMENTAL BIOLOGY LA English DT Article DE pVHL; hypoxia; HIF2 alpha; cytotrophoblast; human placenta; fibronectin ID TUMOR-SUPPRESSOR PROTEIN; ADHESION RECEPTORS; DEFICIENT MICE; HUMAN PLACENTA; IN-VITRO; DIFFERENTIATION; TROPHOBLAST; BINDING; OXYGEN; GENE AB The von Hippel-Lindau tumor-suppressor protein (pVHL) regulates the stability of HIF1 alpha and HIF2 alpha and thus is pivotal in cellular responses to changes in oxygen tension. Paradoxically, human cytotrophoblasts proliferate under hypoxic conditions comparable to those measured in the early gestation placenta (2% O-2), but differentiate into tumorlike invasive cells under well-oxygenated conditions such as those found in the uterus. We sought to explain this phenomenon in terms of pVHL expression. In situ, pVHL immunolocalized to villous cytotrophoblast stem cells, and expression was enhanced at sites of cell column initiation; in both of these relatively hypoxic locations, cytoplasmic staining for HIF2a was also detected. As cytotrophoblasts attached to and invaded the uterus, which results in their increased exposure to oxygen, pVHL staining was abruptly downregulated concordant with localization of HIF2a to the nucleus. In vitro, hypoxia (2% O-2) upregulated cytotrophoblast pVHL expression together with HIF2 alpha, which localized to the cytoplasm; culture under well-oxygenated conditions greatly reduced levels of both molecules. These results, together with the placental defects previously observed in VHL-/- mice, suggest that pVHL is a component of the mechanism that transduces local differences in oxygen tension at the maternal-fetal interface to changes in the biological behavior of cytotrophoblasts. Furthermore, these data provide the first example of oxygen-dependent changes in pVHL abundance. (C) 2001 Academic Press. C1 Univ Calif San Francisco, Dept Stomatol, Div Oral Biol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Dept Cell & Mol Biol, Berkeley, CA 94720 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fisher, SJ (reprint author), Univ Calif San Francisco, Dept Stomatol, Div Oral Biol, HSW 604,513 Parnassus Ave, San Francisco, CA 94143 USA. FU NCI NIH HHS [CA68490]; NHLBI NIH HHS [HL64597]; NICHD NIH HHS [HD26732, HD30367] NR 46 TC 58 Z9 59 U1 0 U2 1 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 MAY 15 PY 2001 VL 233 IS 2 BP 526 EP 536 DI 10.1006/dbio.2001.0231 PG 11 WC Developmental Biology SC Developmental Biology GA 436JB UT WOS:000168931800020 PM 11336512 ER PT J AU Long, CM Suh, HH Catalano, PJ Koutrakis, P AF Long, CM Suh, HH Catalano, PJ Koutrakis, P TI Using time- and size-resolved particulate data to quantify indoor penetration and deposition behavior SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID AERODYNAMIC PARTICLE SIZER; OUTDOOR RELATIONSHIPS; PERSONAL EXPOSURE; IONIC SUBSTANCES; FINE PARTICLES; AIR-POLLUTION; MASS; CALIFORNIA; MORTALITY; SURFACES AB Because people spend approximately 85-90% of their time indoors, it is widely recognized that a significant portion of total personal exposures to ambient particles occurs in indoor environments. Although penetration efficiencies and deposition rates regulate indoor exposures to ambient particles, few data exist on the levels or variability of these infiltration parameters, in particular for time- and size-resolved data. To investigate ambient particle infiltration, a comprehensive particle characterization study was conducted in nine nonsmoking homes in the metropolitan Boston area. Continuous indoor and outdoor PM2.5 and size distribution measurements were made in each of the study homes over weeklong periods. Data for nighttime, nonsource periods were used to quantify infiltration factors for PM2.5 as well as for 17 discrete particle size intervals between 0.02 and 10 mum. Infiltration factors for PM2.5 exhibited large intra- and interhome variability, which was attributed to seasonal effects and home dynamics. As expected, minimum infiltration factors were observed for ultrafine and coarse particles. A physical-statistical model was-used. to estimate size-specific penetration efficiencies and deposition rates for these study homes. Our data show that the penetration efficiency depends on particle size, as well as home characteristics. These results provide new insight on the protective role of the building shell in reducing indoor exposures to ambient particles, especially for tighter (e.g., winterized) homes and for particles with diameters greater than 1 mum. C1 Gradient Corp, Cambridge, MA 02142 USA. Harvard Univ, Dept Environm Hlth, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Long, CM (reprint author), Gradient Corp, 238 Main St, Cambridge, MA 02142 USA. EM clong@gradientcorp.com NR 43 TC 229 Z9 233 U1 19 U2 91 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X EI 1520-5851 J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD MAY 15 PY 2001 VL 35 IS 10 BP 2089 EP 2099 DI 10.1021/es001477d PG 11 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 433LA UT WOS:000168759800027 PM 11393992 ER PT J AU Ludwig, T Fisher, P Ganesan, S Efstratiadis, A AF Ludwig, T Fisher, P Ganesan, S Efstratiadis, A TI Tumorigenesis in mice carrying a truncating Brca1 mutation SO GENES & DEVELOPMENT LA English DT Article DE Brca1; mouse mutant; mammary tumors ID SUPPRESSOR GENE BRCA1; TUMOR-FORMATION; MAMMARY-GLAND; MOUSE AB We generated mouse mutants carrying in the Brca1 locus a modification (Brca1(tr)) that eliminates the C-terminal half of the protein product and obtained results indicating that, depending on genetic background, the missing BRCT and/or other domains are dispensable for survival, but essential for tumor suppression. Most of the apparently hypomorphic Brca1(tr/tr) mutants developed various tumors. Lymphomas were detected at all ages, whereas sarcomas and carcinomas, including breast cancer, appeared after a long latency. The mammary tumors showed striking variability in histopathological patterns suggesting stochastic engagement of tumorigenic pathways in their progression, to which the Brca1(tr/tr) mutation was apparently a late participant. C1 Columbia Univ, Dept Anat & Cell Biol, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, Dept Genet & Dev, New York, NY 10032 USA. Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. RP Ludwig, T (reprint author), Columbia Univ, Dept Anat & Cell Biol, New York, NY 10032 USA. RI Ludwig, Thomas/Q-6484-2016 OI Ludwig, Thomas/0000-0003-3461-2585 FU NCI NIH HHS [R21 CA66224, P01 CA75553] NR 15 TC 93 Z9 96 U1 0 U2 3 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 MAY 15 PY 2001 VL 15 IS 10 BP 1188 EP 1193 DI 10.1101/gad.879201 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 436HN UT WOS:000168930600003 PM 11358863 ER PT J AU Burstein, HJ Kuter, I Campos, SM Gelman, RS Tribou, L Parker, LM Manola, J Younger, J Matulonis, U Bunnell, CA Partridge, AH Richardson, PG Clarke, K Shulman, LN Winer, EP AF Burstein, HJ Kuter, I Campos, SM Gelman, RS Tribou, L Parker, LM Manola, J Younger, J Matulonis, U Bunnell, CA Partridge, AH Richardson, PG Clarke, K Shulman, LN Winer, EP TI Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FIRST-LINE CHEMOTHERAPY; PHASE-II TRIAL; MONOCLONAL-ANTIBODY; INTRAVENOUS VINORELBINE; NAVELBINE; CARCINOMA; RECEPTOR; THERAPY; AGENT AB Purpose: To determine the response rate and toxicity profile of trastuzumab administered concurrently with weekly vinorelbine in women with HER2-overexpressing advanced breast cancer. Patients and Methods: Forty women with HER2-positive (+3 by immunohistochemistry, n = 30; +2 or positive, n = 10) breast cancer were enrolled onto a study of trastuzumab (4 mg/kg x 1, 2 mg/kg weekly thereafter) and vinorelbine (25 mg/m(2) weekly, with dose adjusted each week for neutrophil count). Eighty-two percent of women had received prior chemotherapy as part of adjuvant (30%), metastatic (25%), oh both (28%) treatment, including substantial portions of patients who had previously received either anthracyclines (20%), taxanes (15%), or both types (38%) of chemotherapy. Results: Responses were observed in 30 of 40 patients (overall response rate, 75%, conditional corrected 95% confidence interval, 57% to 89%). The response rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive patients. High response rates were also seen in women treated with second- or third-line therapy, and among patients previously treated with anthracyclines and/or taxanes. Combination therapy was feasible; patients received concurrent trastuzumab and vinorelbine in 93% of treatment weeks. Neutropenia was the only grade 4 toxicity. No patients herd symptomatic heart failure. Grade 2 cardiac toxicity was observed in three patients. Prior cumulative doxorubicin dose in excess of 240 mg/m2 and borderline pre-existing cardiac function were associated with grade 2 cardiac toxicity. Conclusion: Trastuzumab in combination with vinorelbine is highly active in women with HER2-overexpressing advanced breast cancer and is well tolerated. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Div Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 31 TC 263 Z9 273 U1 1 U2 8 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 MAY 15 PY 2001 VL 19 IS 10 BP 2722 EP 2730 PG 9 WC Oncology SC Oncology GA 433JX UT WOS:000168757200016 PM 11352965 ER PT J AU Sekine, H Reilly, CM Molano, ID Garnier, G Circolo, A Ruiz, P Holers, VM Boackle, SA Gilkeson, GS AF Sekine, H Reilly, CM Molano, ID Garnier, G Circolo, A Ruiz, P Holers, VM Boackle, SA Gilkeson, GS TI Complement component C3 is not required for full expression of immune complex glomerulonephritis in MRL/lpr mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; DECAY-ACCELERATING FACTOR; HUMAN MESANGIAL CELLS; GLOMERULAR EPITHELIAL-CELLS; CD59 REGULATE COMPLEMENT; WIRE-LOOP LESIONS; CULTURED RAT; BASEMENT-MEMBRANE; 3RD COMPONENT; EXTRAHEPATIC EXPRESSION AB Complement activation and tissue deposition of complement fragments occur during disease progression in lupus nephritis. Genetic deficiency of some complement components (e.g., Factor B) and infusion of complement inhibitors (e.g., Crry, anti-C5 Ab) protect against inflammatory renal disease. Paradoxically, genetic deficiencies of early components of the classical complement pathway (e.g., C1q, C4, and C2) are associated with an increased incidence of lupus in humans and lupus-like disease in murine knockout strains. Complement protein C3 is the converging point for activation of all three complement pathways and thus plays a critical role in biologic processes mediated by complement activation. To define the role of C3 in lupus nephritis, mice rendered C3 deficient by targeted deletion were backcrossed for eight generations to MRL/lpr mice, a mouse strain that spontaneously develops lupus-like disease. We derived homozygous knockout (C3(-/-)), heterozygous (C3(+/-)), and C3 wild-type (C3(+/+)) MRL/lpr nice. Serum levels of autoantibodies and circulating immune complexes were similar among the three groups. However, there was earlier and significantly greater albuminuria in the C3(-/-) mice compared with the other two groups. Glomerular IgG deposition was also significantly greater in the C3(-/-) mice than in the other two groups, although overall pathologic renal scores were similar. These results indicate that C3 and/or activation of C3 is not required for full expression of immune complex renal disease fn MRL/lpr mice and may in fact play a beneficial role via clearance of immune complexes. C1 Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29425 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL 33125 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. RP Gilkeson, GS (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, 96 Jonathon Lucas St,Suite 912,POB 25063, Charleston, SC 29425 USA. NR 66 TC 89 Z9 89 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 2001 VL 166 IS 10 BP 6444 EP 6451 PG 8 WC Immunology SC Immunology GA 471VC UT WOS:000170948500075 PM 11342671 ER PT J AU Dhond, RP Buckner, RL Dale, AM Marinkovic, K Halgren, E AF Dhond, RP Buckner, RL Dale, AM Marinkovic, K Halgren, E TI Spatiotemporal maps of brain activity underlying word generation and their modification during repetition priming SO JOURNAL OF NEUROSCIENCE LA English DT Article DE word-stem completion; magnetoencephalography; temporal lobe; planum temporale; prefrontal cortex; language; occipital lobe; word form ID POSITRON EMISSION TOMOGRAPHY; DEPTH-RECORDED POTENTIALS; TEMPORAL LANGUAGE AREA; LEFT PREFRONTAL CORTEX; SURFACE-BASED ANALYSIS; FUNCTIONAL MRI; CORTICAL ACTIVITY; FACE PERCEPTION; WORKING-MEMORY; NEURAL SYSTEM AB Spatiotemporal maps of brain activity based on magnetoencephalography were used to observe sequential stages in language processing and their modification during repetition priming. Subjects performed word- stem completion and produced either novel or repeated (primed) words across trials. Activation passes from primary visual cortex (activated at similar to 100 msec after word presentation), to left anteroventral occipital (similar to 180 msec), to cortex in and near Wernicke's (similar to 210 msec) and then Broca's (similar to 370 msec) areas. In addition, a posteroventral temporal area is activated simultaneously with posterosuperior temporal cortex. This area shows an early (similar to 200-245 msec) increase in activation to repeated word stems. In contrast, prefrontal and anterior temporal regions showed activity reductions to repeated word stems late (similar to 365-500 msec) in processing. These results tend to support classical models of language and suggest that an effect of direct item repetition is to allow word-form processing to increase its contribution to task performance while concurrently allowing reductions in time-consuming frontal temporal processing. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Univ Utah, Dept Radiol, Salt Lake City, UT 84105 USA. Washington Univ, Howard Hughes Med Inst, Dept Psychol Radiol & Anat & Neurobiol, St Louis, MO 63130 USA. RP Halgren, E (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NIMH NIH HHS [MH57506]; NINDS NIH HHS [NS18741, R01 NS018741, R01 NS018741-22] NR 61 TC 84 Z9 84 U1 0 U2 0 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 MAY 15 PY 2001 VL 21 IS 10 BP 3564 EP 3571 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 427MQ UT WOS:000168409400031 PM 11331385 ER PT J AU Chen, JF Xu, K Petzer, JP Staal, R Xu, YH Beilstein, M Sonsalla, PK Castagnoli, K Castagnoli, N Schwarzschild, MA AF Chen, JF Xu, K Petzer, JP Staal, R Xu, YH Beilstein, M Sonsalla, PK Castagnoli, K Castagnoli, N Schwarzschild, MA TI Neuroprotection by caffeine and A(2A) adenosine receptor inactivation in a model of Parkinson's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE adenosine receptor; methylxanthine; neurotoxin; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; dopamine transporter; Parkinson's disease; knock-out; mice ID INDUCED NEUROTOXICITY; ANTAGONIST; MICE; ACTIVATION; PROTECTION; RATS; EXCITOTOXICITY; MONKEYS; COFFEE; POTENT AB Recent epidemiological studies have established an association between the common consumption of coffee or other caffeinated beverages and a reduced risk of developing Parkinson's disease (PD). To explore the possibility that caffeine helps prevent the dopaminergic deficits characteristic of PD, we investigated the effects of caffeine and the adenosine receptor subtypes through which it may act in the 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) neurotoxin model of PD. Caffeine, at doses comparable to those of typical human exposure, attenuated MPTP-induced loss of striatal dopamine and dopamine transporter binding sites. The effects of caffeine were mimicked by several A(2A) antagonists (7-(2-phenylethyl)-5-amino-2-(2- furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261), 3,7-dimethyl-1-propargylxanthine, and (E)-1,3-diethyl-8 (KW-6002)-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6- dione) (KW-6002) and by genetic inactivation of the A2A receptor, but not by A(1) receptor blockade with 8-cyclopentyl-1,3-dipropylxanthine, suggesting that caffeine attenuates MPTP toxicity by A(2A) receptor blockade. These data establish a potential neural basis for the inverse association of caffeine with the development of PD, and they enhance the potential of A(2A) antagonists as a novel treatment for this neurodegenerative disease. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Charlestown, MA 02129 USA. Virginia Tech, Dept Chem, Harvey W Peters Ctr, Blacksburg, VA 24061 USA. Univ Med & Dent New Jersey, Dept Neurol, Piscataway, NJ 08854 USA. RP Schwarzschild, MA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, MGH E,Bldg 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG08479, AG18167]; NINDS NIH HHS [NS373403] NR 31 TC 208 Z9 208 U1 6 U2 28 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 MAY 15 PY 2001 VL 21 IS 10 BP art. no. EP RC143 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 427MQ UT WOS:000168409400001 PM 11319241 ER PT J AU Hamilton, ML Guo, ZM Fuller, CD Van Remmen, H Ward, WF Austad, SN Troyer, DA Thompson, I Richardson, A AF Hamilton, ML Guo, ZM Fuller, CD Van Remmen, H Ward, WF Austad, SN Troyer, DA Thompson, I Richardson, A TI A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CHROMATOGRAPHY MASS-SPECTROMETRY; HPLC-ELECTROCHEMICAL DETECTION; ENDOGENOUS OXIDATIVE DAMAGE; BASE DAMAGE; RAT-LIVER; CALORIC RESTRICTION; DIFFERENT TISSUES; ANIMAL-MODELS; C57BL/6 MICE; HUMAN-CELLS AB A major controversy in the area of DNA biochemistry concerns the actual in vivo levels of oxidative damage in DNA. We show here that 8-oxo-2-deoxyguanosine (oxo8dG) generation during DNA isolation is eliminated using the sodium iodide (Nal) isolation method and that the level of oxo8dG in nuclear DNA (nDNA) is almost one-hundredth of the level obtained using the classical phenol method. We found using Nal that the ratio of oxo8dG/10(5) deoxyguanosine (dG) in nDNA isolated from mouse tissues ranged from 0.032 +/- 0.002 for liver to 0.015 +/- 0.003 for brain. We observed a significant increase (10-fold) in oxo8dG in nDNA isolated from liver tissue after 2 Gy of gamma -irradiation when Nal was used to isolate DNA. The turnover of oxo8da in nDNA was rapid, e.g. disappearance of oxo8da in the mouse liver in vivo after gamma -irradiation had a half-life of 11 min. The levels of oxo8da in mitochondrial DNA isolated from liver, heart and brain were 6-, 16- and 23-fold higher than nDNA from these tissues. Thus, our results showed that the steady-state levels of oxo8da in mouse tissues range from 180 to 360 lesions in the nuclear genome and from one to two lesions in 100 mitochondrial genomes. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, Div Urol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Idaho, Dept Biol Sci, Moscow, ID 83844 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Physiol, MSC-7756, San Antonio, TX 78229 USA. OI Fuller, Clifton/0000-0002-5264-3994 FU NIA NIH HHS [P01AG14674, P30 AG013319, R01-AG13319] NR 59 TC 122 Z9 127 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 15 PY 2001 VL 29 IS 10 BP 2117 EP 2126 DI 10.1093/nar/29.10.2117 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 433GW UT WOS:000168752700014 PM 11353081 ER PT J AU Culver, JP Ntziachristos, V Holboke, MJ Yodh, AG AF Culver, JP Ntziachristos, V Holboke, MJ Yodh, AG TI Optimization of optode arrangements for diffuse optical tomography: A singular-value analysis SO OPTICS LETTERS LA English DT Article ID PHOTON DENSITY WAVES; DIFFRACTION TOMOGRAPHY; TURBID MEDIA; BREAST; MRI AB We develope a method to optimize the resolution of diffuse optical tomographic instruments. Singular-value analysis of the tomographic weight matrix associated with specific data types, geometries, and optode arrangements is shown to provide a measure of image resolution. We achieve optimization of device configuration by monitoring the resolution measure described. We introduce this idea and demonstrate its utility by optimizing the spatial sampling interval and field-of-view parameters in the parallel-plane transmission geometry employed for diffuse optical breast imaging. We also compare resolution in transmission and remission geometries. (C) 2001 Optical Society of America. C1 Univ Penn, Dept Phys, Philadelphia, PA 19104 USA. Univ Penn, Dept Astron, Philadelphia, PA 19104 USA. RP Culver, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 14 TC 114 Z9 114 U1 0 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAY 15 PY 2001 VL 26 IS 10 BP 701 EP 703 DI 10.1364/OL.26.000701 PG 3 WC Optics SC Optics GA 431FZ UT WOS:000168622300014 PM 18040425 ER PT J AU Atlas, SJ Keller, RB Chang, YC Deyo, RA Singer, DE AF Atlas, SJ Keller, RB Chang, YC Deyo, RA Singer, DE TI Surgical and nonsurgical management of sciatica secondary to a lumbar disc herniation - Five-year outcomes from the Maine Lumbar Spine Study SO SPINE LA English DT Article DE sciatica; herniated lumbar disc; prospective cohort study; outcome research; lumbar disc surgery; natural history ID LOW-BACK-PAIN; SURGERY; WORKPLACE; STENOSIS; RATES AB Study Design. A prospective cohort study. Objective. To assess 5-year outcomes for patients with sciatica caused by a lumbar disc herniation treated surgically or nonsurgically. Summary of Background Data. There is limited knowledge about long-term treatment outcomes of sciatica caused by a lumbar disc herniation, particularly the relative benefits of surgical and conservative therapy in contemporary clinical practice. Methods. Eligible, consenting patients recruited from the practices of orthopedic surgeons, neurosurgeons, and occupational medicine physicians throughout Maine had baseline interviews with mailed follow-up questionnaires at 3, 6, and 12 months and annually thereafter. Clinical data were obtained at baseline from a physician questionnaire. Outcomes included patient-reported symptoms of leg and back pain, functional status, satisfaction, and employment and compensation status. Results. Of 507 patients initially enrolled, 5-year outcomes were available for 402 (79.3%) patients: 220 (80%) treated surgically and 182 (78.4%) treated nonsurgically. Surgically treated patients had worse baseline symptoms and functional status than those initially treated nonsurgically. By 5 years 19% of surgical patients had undergone at least one additional lumbar spine operation, and 16% of nonsurgical patients had opted for at least one lumbar spine operation. Overall, patients treated initially with surgery reported better outcomes. At the 5-year follow-up, 70% of patients initially treated surgically reported improvement in their predominant symptom (back or leg pain) versus 56% of those initially treated nonsurgically (P < 0.001). Similarly, a larger proportion of surgical patients reported satisfaction with their current status (63% vs. 46%, P < 0.001). These differences persisted after adjustment for other determinants of outcome. The relative advantage of surgery was greatest early in follow-up and narrowed over 5 years. There was no difference in the proportion of patients receiving disability compensation at the 5-year follow-up. The least symptomatic patients at baseline did well regardless of initial treatment, although function improved more in the surgical group. Conclusions. For patients with moderate or severe sciatica, surgical treatment was associated with greater improvement than nonsurgical treatment at 5 years. However, patients treated surgically were as likely to be receiving disability compensation, and the relative benefit of surgery decreased over time. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr,Med Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA 02114 USA. Maine Med Assessment Fdn, Augusta, GA USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Practices Evaluat Ctr,Med Serv, 50 Staniford St, Boston, MA 02114 USA. FU AHRQ HHS [HS-06344, HS-08194, HS-09804] NR 28 TC 122 Z9 134 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAY 15 PY 2001 VL 26 IS 10 BP 1179 EP 1187 DI 10.1097/00007632-200105150-00017 PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 432FU UT WOS:000168682200015 PM 11413434 ER PT J AU Steinman, TI Becker, BN Frost, AE Olthoff, KM Smart, FW Suki, WN Wilkinson, AH AF Steinman, TI Becker, BN Frost, AE Olthoff, KM Smart, FW Suki, WN Wilkinson, AH TI Guidelines for the referral and management of patients eligible for solid organ transplantation SO TRANSPLANTATION LA English DT Review ID HEPATITIS-C-VIRUS; STAGE RENAL-DISEASE; CHILD-TURCOTTE CLASSIFICATION; QUALITY-OF-LIFE; PEDIATRIC LIVER-TRANSPLANTATION; PANCREAS-KIDNEY TRANSPLANTATION; IDIOPATHIC PULMONARY FIBROSIS; CLINICAL-PRACTICE GUIDELINES; HEPATOCELLULAR-CARCINOMA; CYSTIC-FIBROSIS AB Members of the Clinical Practice Committee, American Society of Transplantation, have attempted to define referral criteria for solid organ transplantation. Work done by the Clinical Practice Committee does not represent the official position of the American Society of Transplantation. Recipients for solid organ transplantation are growing in numbers, progressively outstripping the availability of organ donors. As there may be discrepancies in referral practice and, therefore, inequity may exist in terms of access to transplantation, there needs to be uniformity about who should be referred to transplant centers so the system is fair for all patients. A review of the literature that is both generic and organ specific has been conducted so referring physicians can understand the criteria that make the patient a suitable potential transplant candidate, The psychosocial milieu that needs to be addressed is part of the transplant evaluation. Early intervention and evaluation appear to play a positive role in maximizing quality of life for the transplant recipient. There is evidence, especially in nephrology, that the majority of patients with progressive failure are referred to transplant centers at a late stage of disease, Evidence-based medicine forms the basis for medical decision-making about accepting the patient as a transplant candidate. The exact criteria for each organ are detailed, These guidelines reflect consensus opinions, synthesized by the authors after extensive literature review and reflecting the experience at their major transplant centers. These guidelines can be distributed by transplant centers to referring physicians, to aid them in understanding who is potentially an acceptable candidate for transplantation. The more familiar physicians are with the exact criteria for specific organ transplantation, the more likely they are to refer patients at an appropriate stage. Individual transplant centers will make final decisions on acceptability for transplantation based on specific patient factors, It is hoped that this overview will assist insurers/payers in reimbursing transplant centers for solid organ transplantation, based on criteria for acceptability by the transplant community. The selection and management of patients with end-stage organ failure are constantly changing, and future advances may make obsolete some of the criteria mentioned in the guidelines. Most importantly, these are intended to be guidelines, not rules. C1 Harvard Univ, Sch Med, BIDMC, Dialysis Unit, Boston, MA 02215 USA. RP Steinman, TI (reprint author), Harvard Univ, Sch Med, BIDMC, Dialysis Unit, 330 Brookline Ave FD 220, Boston, MA 02215 USA. NR 101 TC 106 Z9 108 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 2001 VL 71 IS 9 BP 1189 EP 1204 DI 10.1097/00007890-200105150-00001 PG 16 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 439DJ UT WOS:000169095300001 PM 11397947 ER PT J AU Vallhonrat, H Williams, WW Dec, GW Keck, S Schoenfeld, D Cosimi, AB Pascual, M AF Vallhonrat, H Williams, WW Dec, GW Keck, S Schoenfeld, D Cosimi, AB Pascual, M TI Complement activation products in plasma after heart transplantation in humans SO TRANSPLANTATION LA English DT Article ID RENAL-ALLOGRAFT REJECTION; CORONARY-ARTERY DISEASE; HUMORAL REJECTION; CARDIAC ALLOGRAFTS; C4D; DEPOSITION; RECIPIENTS; GENERATION; BIOPSIES; INJURY AB Background Complement activation has recently been implicated as a contributing factor to early and late allograft dysfunction in cardiac transplantation. The current study was designed to determine whether measurement of plasma complement fragments C4d and SC5b-9 would be useful in detecting acute rejection or accelerated graft atherosclerosis (AGA) in cardiac allograft recipients. Methods. We measured complement activation products, C4d (classical pathway) and SC5b-9 (terminal pathway), at the time of routine endomyocardial biopsy in heart transplant recipients. Ten patients in the immediate posttransplantation period (0-100 days) and 19 patients more than 6 months after transplantation were studied. Results, No correlation was found between plasma levels of complement activation fragments and the presence of biopsy-proven acute allograft rejection or AG;A (assessed by coronary angiography), However, plasma C4d and SC5b-9 were significantly elevated in 9 of 10 and 7 of 10 patients, respectively, in the immediate posttransplantation period, This was followed by progressive decrease in the levels of C4d and SC5b-9 fragments during the first 4-6 weeks after transplantation. Conclusion, We conclude that measuring plasma levels of fragments C4d and SC5b-9 is not a useful noninvasive method for detecting acute rejection or AGA after heart transplantation However, this study provides further evidence that early complement activation after heart transplantation may play a pathogenic role in allograft injury. C1 Massachusetts Gen Hosp, Renal Unit, Heart Failure & Cardiac Transplantat Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Heart Failure & Cardiac Transplantat Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Heart Failure & Cardiac Transplantat Ctr, Box MZ70, Boston, MA 02114 USA. NR 18 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 2001 VL 71 IS 9 BP 1308 EP 1311 DI 10.1097/00007890-200105150-00022 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 439DJ UT WOS:000169095300022 PM 11397968 ER PT J AU Narod, SA Sun, P Ghadirian, P Lynch, H Isaacs, C Garber, J Weber, B Karlan, B Fishman, D Rosen, B Tung, N Neuhausen, SL AF Narod, SA Sun, P Ghadirian, P Lynch, H Isaacs, C Garber, J Weber, B Karlan, B Fishman, D Rosen, B Tung, N Neuhausen, SL CA Hereditary Ovarian Canc Clinical TI Tubal ligation and risk of ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study SO LANCET LA English DT Article ID BREAST-CANCER; WOMEN; HYSTERECTOMY AB Background In several case-control and prospective studies, tubal ligation has been associated with a decreased risk of invasive epithelial ovarian cancer. We aimed to assess the potential of tubal ligation in reducing the risk of ovarian cancer in women who carry predisposing mutations in the BRCA1 or BRCA2 genes. Methods We did a matched case-control study among women from Canada, the USA, and the UK who had undergone genetic testing and who carried a pathogenic mutation in BRCA1 or BRCA2. Cases were 232 women with a history of invasive ovarian cancer, and controls were 232 women without ovarian cancer, and who had both ovaries intact. Cases and controls were matched for year of birth, country of residence, and mutation (BRCA1 or BRCA2). The odds ratio for developing ovarian cancer was estimated for tubal ligation, adjusting for oral contraceptive use, parity, history of breast cancer, and ethnic group. Findings In an unadjusted analysis among BRCA1 carriers, significantly fewer cases than controls had ever had tubal ligation (30 of 173 [18%] vs 60 of 173 [35%], odds ratio 0.37 [95% CI 0.21-0.63]; p=0.0003). After adjustment for oral contraceptive use, parity, history of breast cancer and ethnic group, the odds ratio was 0.39 (p=0.002). Combination of tubal ligation and past use of an oral contraceptive was associated with an odds ratio of 0.28 (0.15-0.52). No protective effect of tubal ligation was seen among carriers of the BRCA2 mutation. Interpretation Tubal ligation is a feasible option to reduce the risk of ovarian cancer in women with BRCA1 mutations who have completed childbearing. C1 Univ Toronto, Ctr Res Womens Hlth, Toronto, ON M5G 1N8, Canada. Hotel Dieu, CHUM, Epidemiol Res Unit, Montreal, PQ, Canada. Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Hlth Network, Dept Obstet & Gynecol, Toronto, ON, Canada. Beth Israel Deaconess Hosp, Boston, MA USA. Univ Utah, Dept Med Informat, Salt Lake City, UT 84112 USA. RP Narod, SA (reprint author), Univ Toronto, Ctr Res Womens Hlth, 790 Bay St,Room 750, Toronto, ON M5G 1N8, Canada. FU NCI NIH HHS [1RO1 CA 63682, CA 57601, CA 63678, CA61231, CA74415, N01-CN-67000] NR 21 TC 99 Z9 106 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 12 PY 2001 VL 357 IS 9267 BP 1467 EP 1470 DI 10.1016/S0140-6736(00)04642-0 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 431CL UT WOS:000168614300008 PM 11377596 ER PT J AU Walker, RH Brin, MF Sandu, D Gujjari, P Hof, PR Olanow, CW Shashidharan, P AF Walker, RH Brin, MF Sandu, D Gujjari, P Hof, PR Olanow, CW Shashidharan, P TI Distribution and immunohistochemical characterization of torsinA immunoreactivity in rat brain SO BRAIN RESEARCH LA English DT Article DE torsinA; DYT1; dystonia; immunohistochemistry; rat ID DYSTONIA GENE DYT1; MESSENGER-RNA; PARKIN; EXPRESSION; CLONING AB A mutation of the DYT1 gene on chromosome 9q34 has recently been identified as the cause of one form of autosomal-dominantly inherited dystonia. TorsinA, the protein product of this gene, has homology with the family of heat shock proteins, and is found in many peripheral tissues and brain regions. We used a polyclonal antibody to torsinA, developed in our laboratory, to systematically examine the regional distribution of torsinA in rat brain. We find that neurons in all examined structures are immunoreactive for this protein. There is intense immunoreactivity in most neuronal nuclei, with slightly less labeling of cytoplasm and proximal processes. Terminals also are labeled, especially in striatum, neocortex and hippocampus. Double-labeling fluorescence immunohistochemistry using antibodies to neurotransmitters and other neurochemical markers demonstrated that the majority of neurons of all studied neurochemical types are immunoreactive for torsinA. Our findings indicate that torsinA is widely distributed in the central nervous system implicating additional, localized factors, perhaps within the basal ganglia, in the development of dystonia. Many other proteins have a similar widespread distribution, including some which have been implicated in other movement disorders and neurodegenerative processes, such as parkin, alpha -synuclein. ubiquitin and huntingtin. The distribution of torsinA in rat brain as demonstrated by immunohistochemistry contrasts with the results of in situ hybridization studies of torsinA mRNA in human postmortem brain in which a more limited distribution was found. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Bronx Vet Affairs Med Ctr, Dept Neurol 127, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Dept Neurol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, Kastor Neurobiol Aging Labs, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Ophthalmol, New York, NY 10029 USA. RP Walker, RH (reprint author), Bronx Vet Affairs Med Ctr, Dept Neurol 127, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 15 TC 32 Z9 32 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 11 PY 2001 VL 900 IS 2 BP 348 EP 354 DI 10.1016/S0006-8993(01)02302-2 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 429BQ UT WOS:000168496500027 PM 11334819 ER PT J AU Jonsson, ZO Dhar, SK Narlikar, GJ Auty, R Wagle, N Pellman, D Pratt, RE Kingston, R Dutta, A AF Jonsson, ZO Dhar, SK Narlikar, GJ Auty, R Wagle, N Pellman, D Pratt, RE Kingston, R Dutta, A TI Rvb1p and Rvb2p are essential components of a chromatin remodeling complex that regulates transcription of over 5% of yeast genes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RUVB-LIKE PROTEIN; SACCHAROMYCES-CEREVISIAE; SWI/SNF COMPLEX; NUCLEOSOME ARRAYS; BETA-CATENIN; DNA HELICASE; SWI-SNF; EXPRESSION; BINDING; HOMOLOG AB Eukaryotic Rvb1p and Rvb2p are two highly conserved proteins related to the helicase subset of the AAA+ family of ATPases. Conditional mutants in both genes show rapid changes in the transcription of over 5% of yeast genes, with a similar number of genes being repressed and activated. Both Rvb1p and Rvb2p are required for maintaining the induced state of many inducible promoters. ATP binding and hydrolysis by Rvb1p and Rvb2p is individually essential in vivo, and the two proteins are associated with each other in a high molecular weight complex that shows ATP-dependent chromatin remodeling activity in vitro. Our findings show that Rvb1p and Rvb2p are essential components of a chromatin remodeling complex and determine genes regulated by the complex. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Dutta, A (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RI Jonsson, Zophonias/E-1960-2015; Dutta, Anindya/P-3203-2016 FU NCI NIH HHS [CA60499] NR 39 TC 69 Z9 71 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 MAY 11 PY 2001 VL 276 IS 19 BP 16279 EP 16288 DI 10.1074/jbc.M011523200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 431GH UT WOS:000168623100095 PM 11278922 ER PT J AU Neer, RM Arnaud, CD Zanchetta, JR Prince, R Gaich, GA Reginster, JY Hodsman, AB Eriksen, EF Ish-Shalom, S Genant, HK Wang, OH Mitlak, BH AF Neer, RM Arnaud, CD Zanchetta, JR Prince, R Gaich, GA Reginster, JY Hodsman, AB Eriksen, EF Ish-Shalom, S Genant, HK Wang, OH Mitlak, BH TI Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; VITAMIN-D SUPPLEMENTATION; VERTEBRAL FRACTURES; SALMON-CALCITONIN; CALCIUM; INTERMITTENT; ALENDRONATE; RISK; HYPERPARATHYROIDISM; CALCITRIOL AB Background: Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. Methods: We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 mug of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. Results: New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-mug and 40-mug parathyroid hormone groups; the respective relative risks of fracture in the 20-mug and 40-mug groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.86]). As compared with placebo, the 20-mug and 40-mug doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-mug dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache). Conclusions: Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-mug dose increased bone mineral density more than the 20-mug dose but had similar effects on the risk of fracture and was more likely to have side effects. (N Engl J Med 2001;344:1434-41.) Copyright (C) 2001 Massachusetts Medical Society. C1 Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Fdn Invest Metab, Buenos Aires, DF, Argentina. Univ Western Australia, Perth, WA 6009, Australia. Sir Charles Gairdner Hosp, Perth, WA, Australia. Policlin Univ L Brull, Liege, Belgium. St Josephs Hlth Ctr, London, ON, Canada. Aarhus Kommune Hosp, Aarhus, Denmark. Rambam Med Ctr, Haifa, Israel. RP Mitlak, BH (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. NR 31 TC 2194 Z9 2319 U1 18 U2 133 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 10 PY 2001 VL 344 IS 19 BP 1434 EP 1441 DI 10.1056/NEJM200105103441904 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 430BQ UT WOS:000168554000004 PM 11346808 ER PT J AU Peters, DG Klucher, KM Perlingeiro, RCR Dessain, SK Koh, EY Daley, GQ AF Peters, DG Klucher, KM Perlingeiro, RCR Dessain, SK Koh, EY Daley, GQ TI Autocrine and paracrine effects of an ES-cell derived, BCR/ABL-transformed hematopoietic cell line that induces leukemia in mice SO ONCOGENE LA English DT Article DE BCR/ABL; embryonic stem cell; chronic myeloid leukemia; interleukin-3 ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; COLONY-STIMULATING FACTOR; EMBRYONIC STEM-CELLS; BCR-ABL; IN-VITRO; DIFFERENTIATION; GROWTH; EXPRESSION; ONCOGENE AB During differentiation in vitro, Embryonic Stem (ES) cells generate both primitive erythroid and definitive myeloid lineages in a process that mimics hematopoiesis in the mammalian yolk sac, To investigate leukemic transformation of these embryonic hematopoietic progenitors, we infected differentiating cultures of ES cells with the Chronic Myeloid Leukemia-specific BCR/ABL oncoprotein. Following a period of liquid culture, we isolated two transformed subclones, EB57 and EB67, that retained characteristics of embryonic hematopoietic progenitors and induced a fatal leukemia in mice characterized by massive splenomegaly and granulocytosis, Histopathology of the spleen revealed an abundance of undifferentiated blast-like cells. Investigation of the clonal origins of the granulocytes in the peripheral blood demonstrated that the injected donor cells contributed modestly to the granulocyte population while the majority were host-derived, EB57 secretes IL-3 and unidentified cytokines that can stimulate autocrine and paracrine cell proliferation, presumably accounting for the reactive granulocytosis in diseased mice. These BCR/ABL transformed hematopoietic derivatives of ES cells recapitulate the relationship of BCR/ABL expression to IL-3 production that has been described for primitive hematopoietic progenitors from human CML patients, and illustrates the potential for autocrine and paracrine effects of BCR/ABL-infected cells in murine models. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Whitehead Inst, Cambridge, MA 02142 USA. RP Daley, GQ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [CA76418-01, CA86991-01]; NHLBI NIH HHS [K08 HL 04463] NR 35 TC 33 Z9 34 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 10 PY 2001 VL 20 IS 21 BP 2636 EP 2646 DI 10.1038/sj.onc.1204374 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 431VN UT WOS:000168652600004 PM 11420675 ER PT J AU Go, AS Hylek, EM Phillips, KA Chang, YC Henault, LE Selby, JV Singer, DE AF Go, AS Hylek, EM Phillips, KA Chang, YC Henault, LE Selby, JV Singer, DE TI Prevalence of diagnosed atrial fibrillation in adults - National implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID POPULATION AB Context Atrial fibrillation is the most common arrhythmia in elderly persons and a potent risk factor for stroke. However, recent prevalence and projected future numbers of persons with atrial fibrillation are not well described. Objective To estimate prevalence of atrial fibrillation and US national projections of the numbers of persons with atrial fibrillation through the year 2050, Design, Setting, and Patients Cross-sectional study of adults aged 20 years or older who were enrolled in a large health maintenance organization in California and who had atrial fibrillation diagnosed between July 1, 1996, and December 31, 1997, Main Outcome Measures Prevalence of atrial fibrillation in the study population of 1.89 million; projected number of persons in the United States with atrial fibrillation between 1995-2050. Results A total of 17974 adults with diagnosed atrial fibrillation were identified during the study period; 45% were aged 75 years or older. The prevalence of atrial fibrillation was 0.95% (95% confidence interval, 0.94%-0.96%). Atrial fibrillation was more common in men than in women (1.1% vs 0.8%; P<.001). Prevalence increased from 0.1% among adults younger than 55 years to 9.0% in persons aged 80 years or older. Among persons aged 50 years or older, prevalence of atrial fibrillation was higher in whites than in blacks (2.2% vs 1.5%; P<.001). We estimate approximately 2.3 million US adults currently have atrial fibrillation. We project that this will increase to more than 5.6 million (lower bound, 5.0; upper bound, 6.3) by the year 2050, with more than 50% of affected individuals aged 80 years or older. Conclusions Our study confirms that atrial fibrillation is common among older adults and provides a contemporary basis for estimates of prevalence in the United States. The number of patients with atrial fibrillation is likely to increase 2.5-fold during the next 50 years, reflecting the growing proportion of elderly individuals. Coordinated efforts are needed to face the increasing challenge of optimal stroke prevention and rhythm management in patients with atrial fibrillation. C1 Kaiser Permanente No Calif, Div Res, Oakland, CA 94611 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Go, AS (reprint author), Kaiser Permanente No Calif, Div Res, 3505 Boradway,12th Floor, Oakland, CA 94611 USA. FU NIA NIH HHS [AG15478] NR 17 TC 2823 Z9 2961 U1 21 U2 97 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 MAY 9 PY 2001 VL 285 IS 18 BP 2370 EP 2375 DI 10.1001/jama.285.18.2370 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 427NB UT WOS:000168411200029 PM 11343485 ER PT J AU Mann, MB Wu, SJ Rostamkhani, M Tourtellotte, W MacMurray, J Comings, DE AF Mann, MB Wu, SJ Rostamkhani, M Tourtellotte, W MacMurray, J Comings, DE TI Phenylethanolamine N-methyltransferase (PNMT) gene and early-onset Alzheimer disease SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Alzheimer disease; PNMT; norepinephrine; epinephrine ID CHOLINERGIC NEURONS; CEREBRAL-CORTEX; SENILE DEMENTIA; MESSENGER-RNA; EPINEPHRINE; BRAIN; IMMUNOREACTIVITY; ASSOCIATION; EXPRESSION; NUCLEUS AB The activity of human phenylethanolamine N-methyltransferase (PNMT) is reduced in the neurons of those cells in many subcortical areas of the brain that are known to undergo neurodegeneration in Alzheimer disease (AD). Others have reported that PNMT is decreased in brains of persons with AD and that the decrease in enzymatic activity is due to a reduced amount of the enzyme protein. We have previously described two polymorphisms, G-353A and G-148A, in the promoter region of the gene coding for PNMT. These markers were tested for their association with the occurrence of sporadic AD. Genotyping of 131 necropsy confirmed AD cases, and 947 adult nondemented controls were completed. We observed a significant association between both of the PNMT gene polymorphisms and early-onset AD (EOAD) (P less than or equal to 0.007), but not in late-onset AD (LOAD). These data suggest that genetic variation in the promoter of the PNMT gene is associated with increased susceptibility to the sporadic form of EOAD. (C) 2001 Wiley-Liss, Inc. C1 City Hope Natl Med Ctr, Dept Med Genet, Duarte, CA 91010 USA. Calif State Polytech Univ Pomona, Dept Biol Sci, Pomona, CA 91768 USA. Los Angeles Vet Affairs Med Ctr, Dept Neurol, Los Angeles, CA USA. MGI Appl Gemomics, Dept Genomics, Long Beach, CA USA. RP Comings, DE (reprint author), City Hope Natl Med Ctr, Dept Med Genet, 1500 E Duarte Rd, Duarte, CA 91010 USA. OI Mann, Michael/0000-0002-7515-6515 NR 27 TC 21 Z9 21 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 8 PY 2001 VL 105 IS 4 BP 312 EP 316 DI 10.1002/ajmg.1363 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 439KN UT WOS:000169116200002 PM 11378842 ER PT J AU McNamara, DM Holubkov, R Starling, RC Dec, GW Loh, E Torre-Amione, G Gass, A Janosko, K Tokarczyk, T Kessler, P Mann, DL Feldman, AM AF McNamara, DM Holubkov, R Starling, RC Dec, GW Loh, E Torre-Amione, G Gass, A Janosko, K Tokarczyk, T Kessler, P Mann, DL Feldman, AM CA Intervention Myocarditis Acute Car TI Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy SO CIRCULATION LA English DT Article DE cardiomyopathy; immune system; myocarditis; biopsy ID GAMMA-GLOBULIN; MYOCARDITIS; THERAPY; TRANSPLANTATION AB Background-This prospective placebo-controlled trial was designed to determine whether intravenous immune globulin (IVIG) improves left ventricular ejection fraction (LVEF) in adults with recent onset of idiopathic dilated cardiomyopathy or myocarditis. Methods and Results-Sixty-two patients (37 men, 25 women: mean age +/-SD 43.0+/-12.3 years) with recent onset (less than or equal to6 months of symptoms) of dilated cardiomyopathy and LVEF less than or equal to0.40 were randomized to 2 g/kg IVIG or placebo. All underwent an endomyocardial biopsy before randomization, which revealed cellular inflammation in 16%. The primary outcome was change in LVEF at 6 and 12 months after randomization. Overall, LVEF improved from 0.25+/-0.08 to 0.41+/-0.17 at 6 months (P<0.001) and 0.42+/-0.14 (P<0.001 versus baseline) at 12 months. The increase was virtually identical in patients receiving IVIG and those given placebo (6 months: IVIG 0.14+/-0.12, placebo 0.14+/-0.14; 12 months: IVIG 0.16+/-0.12, placebo 0.15+/-0.16). Overall, 31 (56%) of 55 patients at 1 year had an increase in LVEF greater than or equal to0.10 from study entry, and 20 (36%) of 56 normalized their ejection fraction (greater than or equal to0.50). The transplant-free survival rate was 92% at 1 year and 88% at 2 years. Conclusions-These results suggest that for patients with recent-onset dilated cardiomyopathy, IVIG does not augment the improvement in LVEF. However, in this overall cohort, LVEF improved significantly during follow-up, and the short-term prognosis remains favorable. C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Baylor Methodist Hosp, Houston, TX USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Vet Adm Med Ctr, Cardiol Sect, Houston, TX 77211 USA. Vet Adm Med Ctr, Dept Med, Houston, TX 77211 USA. Baylor Coll Med, Houston, TX USA. RP McNamara, DM (reprint author), Univ Pittsburgh, Med Ctr, Heart Failure Sect, S-558 Scaife Hall,200 Lothrop St, Pittsburgh, PA 15213 USA. OI Mann, Douglas /0000-0002-2516-0145 NR 16 TC 242 Z9 253 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 8 PY 2001 VL 103 IS 18 BP 2254 EP 2259 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 431RN UT WOS:000168644500015 PM 11342473 ER PT J AU Chandrasekar, B Smith, JB Freeman, GL AF Chandrasekar, B Smith, JB Freeman, GL TI Ischemia-reperfusion of rat myocardium activates nuclear factor-kappa B and induces neutrophil infiltration via lipopolysaccharide-induced CXC chemokine SO CIRCULATION LA English DT Article DE ischemia; reperfusion; chemokines; inflammation ID GRANULOCYTE CHEMOTACTIC PROTEIN-2; MACROPHAGE INFLAMMATORY PROTEIN-2; FUNCTIONAL-CHARACTERIZATION; POSTISCHEMIC MYOCARDIUM; IN-VIVO; EXPRESSION; INDUCTION; INJURY; INTERLEUKIN-8; CYTOKINE AB Background-Mechanisms by which neutrophils are attracted to the myocardium in ischemia/reperfusion are not fully defined. Lipopolysaccharide-induced CXC chemokine (LIX), cytokine-induced neutrophil chemoattractant (KC), and macrophage inflammatory protein-2 (MIP-2) are rodent chemokines with potent neutrophil-chemotactic activity. The goals of the present study were to evaluate the roles of these chemokines in a rat model of ischemia/reperfusion and to examine the mechanisms of chemokine induction by oxidative stress and cytokines in cultured cardiomyocytes. Methods and Results-Male Wistar-Kyoto rats underwent 45 minutes of ligation of the left anterior descending coronary artery, followed by reperfusion for various periods. Compared with sham-operated controls, myocardium from reperfused animals had higher levels of free radicals, increased neutrophil infiltration evidenced histologically and by elevated myeloperoxidase activity, and increased nuclear factor (NF)-kappaB DNA binding activity. Ischemia-reperfusion also induced the expression of interleukin-1 beta, tumor necrosis factor (TNF)-alpha, LIX, KC, and MIP-2 mRNA and protein. LIX expression was localized to resident myocardial cells, whereas KC and MIP-2 were expressed only in infiltrating inflammatory cells. Neutralization of LIX inhibited 79% of neutrophil infiltration into previously ischemic myocardium. In contrast, neutralization of KC acid MIP-2 reduced neutrophil infiltration by only 28% and 37%, respectively. In cultured cardiomyocytes, LIX expression was induced by oxidative stress or TNF-alpha and was blocked by the NF-kappaB inhibitor pyrrolidinedithiocarbamate. Conclusions-LIX is expressed by resident myocardial cells during ischemia-reperfusion and is induced in cultured cardiomyocytes by oxidative stress or TNF-alpha via NF-kappaB activation. Although KC and MIP-2 are expressed by inflammatory cells infiltrating the myocardium during reperfusion after ischemia, neutrophil recruitment to reperfused rat myocardium is mainly due to cardiomyocyte expression of LTX. C1 Univ Texas, Hlth Sci Ctr, Dept Med, S Texas Vet Healthcare Syst,Audie Murphy Div, San Antonio, TX 78229 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. RP Chandrasekar, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, S Texas Vet Healthcare Syst,Audie Murphy Div, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL-57008] NR 34 TC 145 Z9 161 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 8 PY 2001 VL 103 IS 18 BP 2296 EP 2302 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 431RN UT WOS:000168644500022 PM 11342480 ER PT J AU O'Rourke, RA Chaudhuri, T Shaw, L Berman, DS AF O'Rourke, RA Chaudhuri, T Shaw, L Berman, DS TI Resolution of stress-induced myocardial ischemia during aggressive medical therapy as demonstrated by single photon emission computed tomography imaging SO CIRCULATION LA English DT Editorial Material C1 Univ Texas, Hlth Sci Ctr, Div Cardiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Nucl Med Serv, San Antonio, TX USA. Emory Univ, Dept Hlth Policy & Management, Atlanta, GA 30322 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP O'Rourke, RA (reprint author), Univ Texas, Hlth Sci Ctr, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 0 TC 15 Z9 16 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 MAY 8 PY 2001 VL 103 IS 18 BP 2315 EP 2315 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 431RN UT WOS:000168644500025 PM 11342483 ER PT J AU Rordorf, G Koroshetz, WJ Ezzeddine, MA Segal, AZ Buonanno, FS AF Rordorf, G Koroshetz, WJ Ezzeddine, MA Segal, AZ Buonanno, FS TI A pilot study of drug-induced hypertension for treatment of acute stroke SO NEUROLOGY LA English DT Article ID THERAPY; SAFETY AB The aim of this pilot study was to determine whether the use of induced hypertension in acute stroke is feasible and associated with neurologic improvement. Phenylephrine was used to raise the systolic blood pressure in patients with acute stroke by 20%, not to exceed 200 mmHg. Of 13 patients treated, 7 improved by 2 points on the NIH Stroke Scale. No systemic or neurologic complications were seen. The authors conclude that induced hypertension in acute stroke is feasible and likely safe and can improve the neurologic examination in some patients. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Cornell Univ, Med Ctr, Stroke Serv, New York, NY 10021 USA. RP Rordorf, G (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Blake 1291,55 Fruit St, Boston, MA 02114 USA. NR 9 TC 109 Z9 117 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 MAY 8 PY 2001 VL 56 IS 9 BP 1210 EP 1213 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 428ZU UT WOS:000168492200017 PM 11342689 ER PT J AU Egan, RA Thompson, CR MacCollin, M Lessell, S AF Egan, RA Thompson, CR MacCollin, M Lessell, S TI Monocular elevator paresis in neurofibromatosis type 2 SO NEUROLOGY LA English DT Article ID IMPAIRMENT AB A retrospective review of 29 consecutive unselected patients referred for neuro-ophthalmic evaluation after the diagnosis of neurofibromatosis type 2 (NF2) showed that four of them had a monocular elevator paresis. Ln two of the four MRI demonstrated lesions, presumed to be schwannomas, of the third nerve. These findings indicate that monocular elevator paresis is a common neuro-ophthalmic finding in NF2, which the authors suspect is probably a sign of third nerve infiltration or compression by a schwannoma. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lessell, S (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 9 TC 7 Z9 7 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 MAY 8 PY 2001 VL 56 IS 9 BP 1222 EP 1224 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 428ZU UT WOS:000168492200021 PM 11342693 ER PT J AU Zhang, D Beresford, PJ Greenberg, AH Lieberman, J AF Zhang, D Beresford, PJ Greenberg, AH Lieberman, J TI Granzymes A and B directly cleave lamins and disrupt the nuclear lamina during granule-mediated cytolysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ISOLATED THYMOCYTE NUCLEI; TOXIC LYMPHOCYTES-T; DNA CLEAVAGE; CYTOTOXIC LYMPHOCYTES; APOPTOTIC THYMOCYTES; DISTINCT SUBSTRATE; SERINE PROTEASES; CDC2 KINASE; CELL-DEATH; DEGRADATION AB Cytotoxic T lymphocytes (CTL) induce apoptosis by engaging death receptors or by exocytosis of cytolytic granules containing granzyme (Gzm) proteases and perforin. The lamins, which maintain the structural integrity of the nuclear envelope, are cleaved by caspases during caspase-mediated apoptosis, Although death receptor engagement and GzmB activate caspases, CTL also induce apoptosis during caspase blockade. Both GzmA and GzmB directly and efficiently cleave laminB in vitro, in situ in isolated nuclei and in cells loaded with perforin and Gzms, even in the presence of caspase inhibitors. LaminB is cleaved by GzmA at concentrations of 3 nM, but GzmB is 50 times less active. GzmA cuts laminB at R392; GzmB cuts at the caspase VEVD231 site. Characteristic laminB fragments generated by Gzm proteolysis also are observed during CTL lysis, even in the presence of caspase inhibitors or in cells overexpressing bcl-2. Lamins A/C are direct substrates of GzmA, but not GzmB. GzmA and GzmB therefore directly target critical caspase substrates in caspase-resistant cells. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Manitoba, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [R56 AI045587, AI45587, R01 AI045587] NR 46 TC 98 Z9 103 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 MAY 8 PY 2001 VL 98 IS 10 BP 5746 EP 5751 DI 10.1073/pnas.101329598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 431GK UT WOS:000168623300068 PM 11331782 ER PT J AU Motyckova, G Weilbaecher, KN Horstmann, M Rieman, DJ Fisher, DZ Fisher, DE AF Motyckova, G Weilbaecher, KN Horstmann, M Rieman, DJ Fisher, DZ Fisher, DE TI Linking osteopetrosis end pycnodysostosis: Regulation of cathepsin K expression by the microphthalmia transcription factor family SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BONE-RESORPTION; OSTEOCLAST DIFFERENTIATION; MOUSE; GENE; LIGAND; MICE; DEGRADATION; ACTIVATION; MUTATIONS; PROTEIN AB Various genetic conditions produce dysfunctional osteoclasts resulting in osteopetrosis or osteosclerosis. These include human pycnodysostosis, an autosomal recessive syndrome caused by cathepsin K mutation, cathepsin K-deficient mice, and miff mutant rodent strains. Cathepsin K is a highly expressed cysteine protease in osteoclasts that plays an essential role in the degradation of protein components of bone matrix. Cathepsin K also is expressed in a significant fraction of human breast cancers where it could contribute to tumor invasiveness. Mitf is a member of a helix-loop-helix transcription factor subfamily, which contains the potential dimerization partners TFE3, TFEB, and TFEC. In mice, dominant negative, but not recessive, mutations of miff, produce osteopetrosis, suggesting a functional requirement for other family members. Miff also has been found-and TFE3 has been suggested-to modulate age-dependent changes in osteoclast function. This study identifies cathepsin K as a transcriptional target of Miff and TFE3 via three consensus elements in the cathepsin K promoter. Additionally, cathepsin K mRNA and protein were found to be deficient in mitf mutant osteoclasts, and overexpression of wild-type Mitf dramatically up-regulated expression of endogenous cathepsin K in cultured human osteoclasts. Cathepsin K promoter activity was disrupted by dominant negative, but not recessive, mouse alleles of mitf in a pattern that closely matches their osteopetrotic phenotypes. This relationship between cathepsin K and the Mitf family helps explain the phenotypic overlap of their corresponding deficiencies in pycnodysostosis and osteopetrosis and identifies likely regulators of cathepsin K expression in bone homeostasis and human malignancy. C1 Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. SmithKline Beecham Pharmaceut, Dept Bone & Cartilage Biol, King Of Prussia, PA 19406 USA. Univ Massachusetts, Med Ctr, Dept Cardiol, Worcester, MA 01655 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Div Pediat Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. NR 29 TC 142 Z9 148 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 8 PY 2001 VL 98 IS 10 BP 5798 EP 5803 DI 10.1073/pnas.091479298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 431GK UT WOS:000168623300077 PM 11331755 ER PT J AU Yoshimura, S Takagi, Y Harada, J Teramoto, T Thomas, SS Waeber, C Bakowska, JC Breakefield, XO Moskowitz, MA AF Yoshimura, S Takagi, Y Harada, J Teramoto, T Thomas, SS Waeber, C Bakowska, JC Breakefield, XO Moskowitz, MA TI FGF-2 regulation of neurogenesis in adult hippocampus after brain injury SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fibroblast growth factor; cerebral ischemia; seizure; gene delivery ID FIBROBLAST-GROWTH-FACTOR; FOCAL CEREBRAL-ISCHEMIA; TRANSIENT GLOBAL-ISCHEMIA; KAINATE-INDUCED SEIZURES; HERPES-SIMPLEX VIRUS; DENTATE GYRUS; PLASMINOGEN-ACTIVATOR; RAT-BRAIN; CORTICAL NEUROGENESIS; GENE-TRANSFER AB Fibroblast growth factor-2 (FGF-2) promotes proliferation of neuroprogenitor cells in culture and is up-regulated within brain after injury, Using mice genetically deficient in FGF-2 (FGF-2(-/-) mice), we addressed the importance of endogenously generated FGF-2 on neurogenesis within the hippocampus, a structure involved in spatial, declarative, and contextual memory, after seizures or ischemic injury. BrdUrd incorporation was used to mark dividing neuroprogenitor cells and NeuN expression to monitor their differentiation into neurons. In the wild-type strain, hippocampal FGF-2 increased after either kainic acid injection or middle cerebral artery occlusion, and the numbers of BrdUrd/NeuN-positive cells significantly increased on days 9 and 16 as compared with the controls. In FGF-2(-/-) mice, BrdUrd labeling was attenuated after kainic acid or middle cerebral artery occlusion, as was the number of neural cells colabeled with both BrdUrd and NeuN. After FGF2(-/-) mice were injected intraventricularly with a herpes simplex virus-1 amplicon vector carrying FGF-2 gene, the number of BrdUrd-labeled cells increased significantly to values equivalent to wild-type littermates after kainate seizures. These results indicate that endogenously synthesized FGF-2 is necessary and sufficient to stimulate proliferation and differentiation of neuroprogenitor cells in the adult hippocampus after brain insult. C1 Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurosurg & Neurol, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit,Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02129 USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Dept Neurosurg & Neurol, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NIMH NIH HHS [MH60587]; NINDS NIH HHS [5 P50 NS10828, NS24279, P01 NS024279, P50 NS010828] NR 52 TC 314 Z9 353 U1 1 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 MAY 8 PY 2001 VL 98 IS 10 BP 5874 EP 5879 DI 10.1073/pnas.101034998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 431GK UT WOS:000168623300090 PM 11320217 ER PT J AU Furuta, GT Turner, JR Taylor, CT Hershberg, RM Comerford, K Narravula, S Podolsky, DK Colgan, SP AF Furuta, GT Turner, JR Taylor, CT Hershberg, RM Comerford, K Narravula, S Podolsky, DK Colgan, SP TI Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE epithelium; gastrointestinal disease; transcription factor; intestinal permeability; endothelium ID UBIQUITIN-PROTEASOME PATHWAY; ELEMENT-BINDING PROTEIN; GENE-EXPRESSION; EPITHELIAL-CELLS; FACTOR 1-ALPHA; FACTOR-I; SURFACE; OXYGEN; ACTIVATION; GROWTH AB Mucosal organs such as the intestine are supported by a rich and complex underlying vasculature. For this reason, the intestine, and particularly barrier-protective epithelial cells. are susceptible to damage related to diminished blood flow and concomitant tissue hypoxia. We sought to identify compensatory mechanisms that protect epithelial barrier during episodes of intestinal hypoxia. Initial studies examining T84 colonic epithelial cells revealed that barrier function is uniquely resistant to changes elicited by hypoxia. A search for intestinal-specific. barrier-protective factors revealed that the human intestinal trefoil factor (ITF) gene promoter bears a previously unappreciated binding site for hypoxia-inducible factor (HIF)-1. Hypoxia resulted in parallel induction of ITF mRNA and protein. Electrophoretic mobility shift assay analysis using ITF-specific, HIF-1 consensus motifs resulted in a hypoxia-inducible DNA binding activity, and loading cells with antisense oligonucleotides directed against the alpha chain of HIF-1 resulted in a loss of ITF hypoxia inducibility. Moreover, addition of anti-ITF antibody resulted in a loss of barrier function in epithelial cells exposed to hypoxia, and the addition of recombinant. human ITF to vascular endothelial cells partially protected endothelial cells from hypoxia-elicited barrier disruption. Extensions of these studies in vivo revealed prominent hypoxia-elicited increases in intestinal permeability in ITF null mice. HIF-1-dependent induction of ITF may provide an adaptive link for maintenance of barrier function during hypoxia. C1 Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Childrens Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. RP Colgan, SP (reprint author), Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Thorn Bldg 704,20 Shattuck St, Boston, MA 02115 USA. RI Colgan, Sean/B-4573-2009; Turner, Jerrold/A-6895-2009 OI Turner, Jerrold/0000-0003-0627-9455 FU NHLBI NIH HHS [HL60569, R01 HL060569]; NIDDK NIH HHS [DK02503, DK02564, DK02682, DK50189, P30 DK043351, R01 DK050189, R29 DK050189, R37 DK050189] NR 44 TC 204 Z9 217 U1 0 U2 11 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 MAY 7 PY 2001 VL 193 IS 9 BP 1027 EP 1034 DI 10.1084/jem.193.9.1027 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 432DX UT WOS:000168677900005 PM 11342587 ER PT J AU Farzan, M Schnitzler, CE Vasilieva, N Leung, D Kuhn, J Gerard, C Gerard, NP Choe, H AF Farzan, M Schnitzler, CE Vasilieva, N Leung, D Kuhn, J Gerard, C Gerard, NP Choe, H TI Sulfated tyrosines contribute to the formation of the C5a docking site of the human C5a anaphylatoxin receptor SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE C5a; C5aR; tyrosine sulfation; chemotactic receptors; CD88 ID N-TERMINAL REGION; HIV-1 ENTRY; ENVELOPE GLYCOPROTEIN; LIGAND-BINDING; CCR5; IDENTIFICATION; MUTAGENESIS; RESIDUES; DOMAIN; ANTIBODIES AB The complement anaphylatoxin C5a and its seven-transmembrane segment (7TMS) receptor play an important role in host defense and in a number of inflammation-associated pathologies. The NH2-terminal domain of the C5a receptor (C5aR/CD88) contributes substantially to its ability to bind C5a. Here we show that the tyrosines at positions 11 and 14 of the C5aR are posttranslationally modified by the addition of sulfate groups. The sulfate moieties of each of these tyrosines are critical to the ability of the C5aR to bind C5a and to mobilize calcium. A C5aR variant lacking these sulfate moieties efficiently mobility calcium in response to a small peptide agonist, but not to C5a, consistent with a two-site model of ligand association in which the tyrosine-sulfated region of the C5aR mediates the initial docking interaction. A peptide based on the NH2 terminal of the C5aR and sulfated at these two tyrosines, but not its unsulfated analogue or a doubly sulfated control peptide, partially inhibited C5a association with its receptor. These observations clarify structural and mutagenic studies of the C5a/C5aR association and suggest that related 7TMS receptors are also modified by functionally important sulfate groups on their NH2-terminal tyrosines. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Med,Perlmutter Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Choe, H (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Med,Perlmutter Lab, Boston, MA 02115 USA. RI Kuhn, Jens H./B-7615-2011; Schnitzler, Christine/G-8733-2013; Leung, Doris/R-5447-2016 OI Kuhn, Jens H./0000-0002-7800-6045; Leung, Doris/0000-0002-2558-7798 FU NHLBI NIH HHS [R01 HL036162, HL36162, R37 HL036162]; NIAID NIH HHS [AI28691, AI41851, AI43891, P30 AI028691, R01 AI041851, R01 AI043891] NR 28 TC 57 Z9 60 U1 0 U2 5 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 MAY 7 PY 2001 VL 193 IS 9 BP 1059 EP 1065 DI 10.1084/jem.193.9.1059 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 432DX UT WOS:000168677900008 PM 11342590 ER PT J AU Mathew, A MacLean, JA DeHaan, E Tager, AM Green, FHY Luster, AD AF Mathew, A MacLean, JA DeHaan, E Tager, AM Green, FHY Luster, AD TI Signal transducer and activator of transcription 6 controls chemokine production and T helper cell type 2 cell trafficking in allergic pulmonary inflammation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE asthma; cytokines; eosinophil; transcription factor; knockout mouse ID INDUCED AIRWAY HYPERRESPONSIVENESS; VASCULAR ENDOTHELIAL-CELLS; TH2 CELLS; CC-CHEMOKINE; EPITHELIAL-CELLS; EOTAXIN EXPRESSION; LUNG INFLAMMATION; T-HELPER-2 CELLS; MUCUS PRODUCTION; P-SELECTIN AB Antigen-specific CD4 T helper type 2 (Th2) cells play a pivotal role in the induction of allergic asthma, but the mechanisms regulating their recruitment into the airways are unknown. Signal transducer and activator of transcription factor (Stat)6 is a transcription factor essential for Th2 cell differentiation. Here we show that Stat6 also controls Th2 cell recruitment and effector function in allergic inflammation in vivo. To isolate the role of Stat6 in regulating Th2 cell trafficking and effector function from its role in Th2 cell differentiation, we used a murine model of asthma in which in vitro-differentiated Stat6(+/+) antigen-specific Th2 cells were adoptively transferred into naive Stat6(-/-) and Stat6(+/+) mice followed by aerosol antigen challenge. We found that all of the features of asthma, including Th2 cell accumulation, Th2 and eosinophil-active chemokine production, and airway eosinophilia, mucus production, and hyperresponsiveness seen in Stat6(+/+) mice, were dramatically absent in Stat6(-/-) mice that received Stat6(+/+) antigen-specific Th2 cells. Our findings establish Stat6 as essential for the Th2 cell trafficking and effector function and suggest that interruption of Stat6 signaling in resident cells of the lung is a novel approach to asthma therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Univ Calgary, Dept Pathol, Calgary, AB T2N 1N4, Canada. RP Luster, AD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Bldg 149,13th St, Boston, MA 02114 USA. FU NHLBI NIH HHS [F32-HL10375-01, F32 HL010375]; NIAID NIH HHS [R01-AI40618] NR 47 TC 134 Z9 147 U1 0 U2 5 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 MAY 7 PY 2001 VL 193 IS 9 BP 1087 EP 1096 DI 10.1084/jem.193.9.1087 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 432DX UT WOS:000168677900011 PM 11342593 ER PT J AU Baekkevold, ES Yamanaka, T Palframan, RT Carlsen, HS Reinholt, FP von Andrian, UH Brandtzaeg, P Haraldsen, G AF Baekkevold, ES Yamanaka, T Palframan, RT Carlsen, HS Reinholt, FP von Andrian, UH Brandtzaeg, P Haraldsen, G TI The CCR7 ligand ELC (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE chemokines; lymphocyte trafficking; vascular endothelium; lymphoid tissue; plt/plt mice ID SECONDARY LYMPHOID ORGANS; DENDRITIC CELLS; IMMUNE-RESPONSE; CHEMOKINES; LYMPHOCYTES; MIGRATION; ARREST; MOUSE; NODES; MICROENVIRONMENTS AB Lymphocyte homing to secondary lymphoid tissue is defined by a multistep sequence of interactions between lymphocytes and endothelial cells in high endothelial venules (HEVs). After initial selectin-mediated tethering and rolling, firm adhesion of lymphocytes requires rapid up-regulation of lymphocyte integrin adhesiveness. This step is mediated in part by the HEV-derived chemokine SLC (secondary lymphoid-tissue chemokine, or CCL21) that binds to the CC chemokine receptor (CCR)7 on lymphocytes. However, the CC chemokine ELC (Epstein-Barr virus-induced molecule 1 ligand chemokine, or CCL19) shares the same receptor, and ELC transcripts have been observed in the T cell areas of lymphoid organs. Here, we show that perivascular ELC is transcytosed to the luminal surfaces of HEVs and enables efficient T cell homing to lymph nodes. In situ hybridization on sections of human tonsil showed no ELC mRNA in HEVs, but immunostaining revealed ELC protein in cytoplasmic vesicles of HEV cells. Furthermore, ELC injected into the footpads of mice entered the draining lymph nodes and was presented by HEVs. Finally, intracutaneous injections of ELC in mice lacking functionally relevant ELC and SLC (plt/plt mice) restored T cell trafficking to draining lymph nodes as efficiently as SLC. We conclude that perivascular ELC is transcytosed to the luminal surfaces of HEVs and participates in CCR7-mediated triggering of lymphocyte arrest. C1 Univ Oslo, Rikshosp, Lab Immunohistochem & Immunopathol, N-0027 Oslo, Norway. Univ Oslo, Rikshosp, Inst Pathol, Electron Microscopy Lab, N-0027 Oslo, Norway. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Baekkevold, ES (reprint author), Univ Oslo, Rikshosp, Lab Immunohistochem & Immunopathol, N-0027 Oslo, Norway. RI von Andrian, Ulrich/A-5775-2008; Haraldsen, Guttorm/I-2680-2013 FU NHLBI NIH HHS [HL54936, HL56946, HL62524, P01 HL056949, R01 HL054936] NR 29 TC 239 Z9 242 U1 0 U2 4 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 MAY 7 PY 2001 VL 193 IS 9 BP 1105 EP 1111 DI 10.1084/jem.193.9.1105 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 432DX UT WOS:000168677900013 PM 11342595 ER PT J AU Tapon, N Ito, N Dickson, BJ Treisman, JE Hariharan, IK AF Tapon, N Ito, N Dickson, BJ Treisman, JE Hariharan, IK TI The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation SO CELL LA English DT Article ID EKER RAT MODEL; TSC2 GENE; CYCLIN-E; S-PHASE; PHOSPHOINOSITIDE 3-KINASE; IMAGINAL DISC; PRODUCT; SIZE; HAMARTIN; EYE AB The inherited human disease tuberous sclerosis, characterized by hamartomatous tumors, results from mutations in either TSC1 or TSC2. We have characterized mutations in the Drosophila Tsc1 and Tsc2/gigas genes. Inactivating mutations in either gene cause an identical phenotype characterized by enhanced growth and increased cell sire with no change in ploidy. Overall, mutant cells spend less time in G1. Coexpression of both Tsc1 and Tsc2 restricts tissue growth and reduces cell size and cell proliferation. This phenotype is modulated by manipulations in cyclin levels. In postmitotic mutant cells, levels of Cyclin E and Cyclin A are elevated. This correlates with a tendency for these cells to reenter the cell cycle inappropriately as is observed in the human lesions. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Mol Neurogenet Unit, Charlestown, MA 02129 USA. Res Inst Mol Pathol, A-1030 Vienna, Austria. NYU, Med Ctr, Skirball Inst Biomol Med, New York, NY 10016 USA. NYU, Med Ctr, Dept Cell Biol, New York, NY 10016 USA. RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NEI NIH HHS [EY11632]; NIGMS NIH HHS [GM61672] NR 46 TC 392 Z9 401 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 4 PY 2001 VL 105 IS 3 BP 345 EP 355 DI 10.1016/S0092-8674(01)00332-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 429KL UT WOS:000168515900004 PM 11348591 ER PT J AU Lu, CF Takagi, J Springer, TA AF Lu, CF Takagi, J Springer, TA TI Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; INTERCELLULAR-ADHESION MOLECULE-1; POLYMERASE CHAIN-REACTION; I-DOMAIN; CELL-ADHESION; MAC-1 CD11B/CD18; LIGAND-BINDING; T-CELL; CR3-DEPENDENT ADHESION; MONOCLONAL-ANTIBODY AB The adhesiveness of integrins is regulated through a process termed "inside-out" signaling. To understand the molecular mechanism of integrin inside-out signaling, we generated K562 stable cell lines that expressed LFA-1 (alpha (L)beta (2)) Or Mac-1 (alpha (M)beta (2)) with mutations in the cytoplasmic domain. Complete truncation of the beta (2) cytoplasmic domain, but not a truncation that retained the membrane proximal eight residues, resulted in constitutive activation of alpha (L)beta (2) and alpha (M)beta (2) demonstrating the importance of this membrane proximal region in the regulation of integrin adhesive function. Furthermore, replacement of the alpha (L) and beta (2) cytoplasmic domains with acidic and basic peptides that form an alpha -helical coiled coil caused inactivation of alpha (L)beta (2). Association of these artificial cytoplasmic domains was directly demonstrated. By contrast, replacement of the alpha (L) and beta (2) cytoplasmic domains with two basic peptides that do not form an alpha -helical coiled coil activated alpha (L)beta (2). Induction of ligand binding by the activating cytoplasmic domain mutations correlated with the induction of activation epitopes in the extracellular domain. Our data demonstrate that cytoplasmic, membrane proximal association between integrin alpha and beta subunits, constrains an integrin in the inactive conformation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NCI NIH HHS [CA31799, CA31798] NR 50 TC 128 Z9 133 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 MAY 4 PY 2001 VL 276 IS 18 BP 14642 EP 14648 DI 10.1074/jbc.M100600200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 429QQ UT WOS:000168528800018 PM 11279101 ER PT J AU Mizuguchi, G Vassilev, A Tsukiyama, T Nakatani, Y Wu, C AF Mizuguchi, G Vassilev, A Tsukiyama, T Nakatani, Y Wu, C TI ATP-dependent nucleosome remodeling and histone hyperacetylation synergistically facilitate transcription of chromatin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID RNA-POLYMERASE-II; SOLUBLE NUCLEAR FRACTION; SWI-SNF COMPLEX; IN-VITRO; ACETYLTRANSFERASE COMPLEXES; DROSOPHILA EMBRYOS; SACCHAROMYCES-CEREVISIAE; ACTIVATION DOMAIN; SWI/SNF COMPLEX; GENE-EXPRESSION AB Drosophila nucleosome remodeling factor (NURF) is an ISWI-containing protein complex that facilitates nucleosome mobility and transcriptional activation in an ATP-dependent manner. Numerous studies have implicated histone acetylation in transcriptional activation. We investigated the relative contributions of these two chromatin modifications to transcription in vitro of a chromatinized adenovirus E4 minimal promoter that contains binding sites for the GAL4-VP16 activator. We found that NURF could remodel chromatin and stimulate transcription irrespective of the acetylation status of histones, In contrast, hyperacetylation of histones in the absence of NURF was unable to stimulate transcription, suggesting that NURF-dependent chromatin remodeling is an obligatory step in E4 promoter activation. When chromatin templates were first hyperacetylated and then incubated with NURF, significantly greater transcription stimulation was observed. The results suggest that changes in chromatin induced by acetylation of histones and the mobilization of nucleosomes by NURF combine synergistically to facilitate transcription. Experiments using single and multiple rounds of transcription indicate that these chromatin modifications stimulate transcription preinitiation as well as reinitiation. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Kyoto Univ, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068502, Japan. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 104 TC 48 Z9 48 U1 2 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 MAY 4 PY 2001 VL 276 IS 18 BP 14773 EP 14783 DI 10.1074/jbc.M100125200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 429QQ UT WOS:000168528800034 PM 11279013 ER PT J AU Fitzgerald, ML Mendez, AJ Moore, KJ Andersson, LP Panjeton, HA Freeman, MW AF Fitzgerald, ML Mendez, AJ Moore, KJ Andersson, LP Panjeton, HA Freeman, MW TI ATP-binding cassette transporter A1 contains an NH2-terminal signal anchor sequence that translocates the protein's first hydrophilic domain to the exoplasmic space SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TANGIER-DISEASE; CHOLESTEROL EFFLUX; MONOCLONAL-ANTIBODIES; CELLULAR CHOLESTEROL; HDL CHOLESTEROL; ABCA1 GENE; MUTATIONS; RECEPTOR; PROMOTER; CLONING AB Mutations in the ATP-binding cassette transporter A1 (ABCA1) transporter are associated with Tangier disease and a defect in cellular cholesterol efflux, The amino terminus of the ABCA1 transporter has two putative in-frame translation initiation sites, 60 amino acids apart. A cluster of hydrophobic amino acids form a potentially cleavable signal sequence in this 60-residue extension. We investigated the functional role of this extension and found that it was required for stable protein expression of transporter constructs containing any downstream transmembrane domains. The extension directed transporter translocation across the ER membrane with an orientation that resulted in glycosylation of amino acids immediately distal to the signal sequence. Neither the native signal sequence nor a green fluorescent protein tag, fused at the amino terminus, was cleaved from ABCA1. The green fluorescent protein fusion protein had efflux activity comparable with wild type ABCA1 and demonstrated a predominantly plasma membrane distribution in transfected cells. These data establish a requirement for the upstream 60 amino acids of ABCA1. This region contains an uncleaved signal anchor sequence that positions the amino terminus in a type II orientation leading to the extracellular presentation of an similar to 600-amino acid loop in which loss-of-function mutations cluster in Tangier disease patients. C1 Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Miami, Sch Med, Diabet Res Inst, Miami, FL 33101 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [UO1-HL-66678, HL10398, HL53451, HL56985, HL45098] NR 39 TC 87 Z9 90 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 MAY 4 PY 2001 VL 276 IS 18 BP 15137 EP 15145 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 429QQ UT WOS:000168528800082 PM 11328826 ER PT J AU Calvert, PD Govardovskii, VI Krasnoperova, N Anderson, RE Lem, J Makino, CL AF Calvert, PD Govardovskii, VI Krasnoperova, N Anderson, RE Lem, J Makino, CL TI Membrane protein diffusion sets the speed of rod phototransduction SO NATURE LA English DT Article ID PHOTORECEPTOR LIGHT ADAPTATION; LATERAL DIFFUSION; OUTER SEGMENT; LIPID BILAYERS; RETINAL RODS; IN-VIVO; RHODOPSIN; TRANSDUCIN; PHOTORESPONSE; ACTIVATION AB Retinal rods signal the activation of a single receptor molecule by a photon(1). To ensure efficient photon capture, rods maintain about 10(9) copies of rhodopsin densely packed into membranous disks(2). But a high packing density of rhodopsin may impede other steps in phototransduction that take place on the disk membrane(3), by restricting the lateral movement of, and hence the rate of encounters between, the molecules involved(4-6). Although it has been suggested that lateral diffusion of proteins on the membrane sets the rate of onset of the photoresponse(7), it was later argued that the subsequent processing of the complexes was the main determinant of this rate(8,9). The effects of protein density on response shut-off have not been reported. Here we show that a roughly 50% reduction in protein crowding achieved by the hemizygous knockout of rhodopsin in transgenic mice accelerates the rising phases and recoveries of flash responses by about 1.7-fold in vivo. Thus, in rods the rates of both response onset and recovery are set by the diffusional encounter frequency between proteins on the disk membrane. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. New England Med Ctr, Dept Ophthalmol, Mol Cardiol Res Inst, Boston, MA 02111 USA. New England Med Ctr, Dept Genet, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Dean A McGee Eye Inst, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Dean A McGee Eye Inst, Oklahoma City, OK 73104 USA. RP Calvert, PD (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. NR 30 TC 120 Z9 121 U1 1 U2 7 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 3 PY 2001 VL 411 IS 6833 BP 90 EP 94 DI 10.1038/35075083 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 427XY UT WOS:000168432800049 PM 11333983 ER PT J AU Barry, MJ AF Barry, MJ TI Prostate-specificy-antigen testing for early diagnosis of prostate cancer. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; MULTICENTER CLINICAL-TRIAL; DIGITAL RECTAL EXAMINATION; 4.0 NG/ML; MEN 50; PSA; EJACULATION; HYPERPLASIA; UROLOGISTS; MORTALITY C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, 50 Staniford St,9th Fl, Boston, MA 02114 USA. FU AHRQ HHS [HS 08397] NR 37 TC 199 Z9 202 U1 1 U2 12 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 3 PY 2001 VL 344 IS 18 BP 1373 EP 1377 DI 10.1056/NEJM200105033441806 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 427NY UT WOS:000168413500006 PM 11333995 ER PT J AU Jadvar, H Fischman, AJ AF Jadvar, H Fischman, AJ TI Evaluation of pancreatic carcinoma with FDG PET SO ABDOMINAL IMAGING LA English DT Article DE PET; FDG; CT; CA 19-9; pancreas; cancer ID POSITRON EMISSION TOMOGRAPHY; PHASE HELICAL CT; F-18 FLUORODEOXYGLUCOSE; PREOPERATIVE ASSESSMENT; DUCTAL ADENOCARCINOMA; CANCER; DIAGNOSIS; GEMCITABINE; DISEASE; CA19-9 AB Background: To assess the diagnostic usefulness and clinical impact of positron emission tomography with [F-18]fluorodeoxyglucose (FDG PET) on the management of patients with known or suspected pancreatic carcinoma. Methods: Attenuation-corrected FDG PET was performed in 20 patients (12 male, eight female) with pancreatic carcinoma at the time of initial diagnosis (n = 7), for tumor surveillance after Whipple surgery (n = 11), and for reevaluation after chemoradiation therapy (n = 2). Visual analysis of PET images were correlated with the results of abdominal computed tomography (CT) and carbohydrate antigen (CA) 19-9 serum tumor marker level that were obtained within 1 month of the PET study. Diagnostic validation was by histology in nine patients and by clinical or radiologic follow-up (5-48 months) in 11 patients. Changes in therapeutic management that were prompted by PET were tabulated. Results: PET was concordant with the findings of abdominal CT in 14 patients (13 true positive, 1 true negative). PET detected clinically unsuspected lung lesions, confirmed subsequently by a chest CT, in one of these 14 patients. PET was discordant with CT in six patients. PET detected tumor recurrence in three patients in this group (15% of total) with nondiagnostic CT findings and elevated CA 19-9 serology. In two of these three patients, chemotherapy with gemcitabine was initiated based on PET localization of disease. Tumor was confirmed in the remaining one of the three patients at autopsy shortly after the PET study. FDG localization in a displaced loop of bowel resulted in an apparent false-positive hepatic lesion in one of six patients in the discordant group. PET underestimated the extent of metastatic disease in the remaining two of six patients due to hyperglycemia, Conclusion: In patients with suspected pancreatic carcinoma at the time of initial presentation, PET is complementary to abdominal CT and allows detection of unsuspected distant metastases. In patients with suspected recurrent pancreatic carcinoma, based on elevated or rising CA 19-9 serology, PET can localize the disease when abdominal CT is nondiagnostic as a result of posttherapy anatomic alteration. Imaging evaluation with PET may impact the clinical management of patients with pancreatic carcinoma. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Nucl Med, Boston, MA 02114 USA. RP Jadvar, H (reprint author), Univ So Calif, Keck Sch Med, Dept Radiol, Div Nucl Med, 1200 N State St,GNH 5250, Los Angeles, CA 90033 USA. NR 40 TC 33 Z9 36 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD MAY-JUN PY 2001 VL 26 IS 3 BP 254 EP 259 DI 10.1007/s002610000159 PG 6 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 428PR UT WOS:000168470500004 PM 11429948 ER PT J AU Crowley, WF Thier, SO AF Crowley, WF Thier, SO TI A program to facilitate clinical research in an AHC: The first five years SO ACADEMIC MEDICINE LA English DT Article AB The authors describe the first five years, 1996-2000, of the Clinical Research Program (CRP) at the Massachusetts General Hospital (MC;H). The CRP was established to improve the quality and increase the quantity of clinical research within the MGH, and has concentrated on three areas: translational research, clinical trials, and outcomes research/epidemiology. The authors describe the CRP's efforts and strategies in these areas in detail, and explain the nature of the workforce, training, resources, and other factors that the CRP has brought to bear in fostering the goals in each area. The CRP's organization is also described, focusing on its administrative core and five units (e.g., the Education Unit), each of which has a distinct function in fostering clinical research. The success of the GRP's work can be measured in several ways, including greatly increased revenues from clinical trials and a large jump in the numbers of registrants for CRP courses. The authors state that CRP-type programs are essential for academic health centers (AHCs) that wish to maintain a balanced portfolio in clinical investigation in the future. They believe that AHCs that can afford to should invest in fostering their unique ability to train clinical investigators and generate new therapies for the future. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Partners HealthCare Inc, Boston, MA USA. RP Crowley, WF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bartlett Hall,Extens 5, Boston, MA 02114 USA. NR 1 TC 11 Z9 11 U1 1 U2 2 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 MAY PY 2001 VL 76 IS 5 BP 403 EP 409 DI 10.1097/00001888-200105000-00006 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 430JU UT WOS:000168571400005 PM 11346512 ER PT J AU Gordon, JA Wilkerson, WM Shaffer, DW Armstrong, EG AF Gordon, JA Wilkerson, WM Shaffer, DW Armstrong, EG TI "Practicing" medicine without risk: Students' and educators' responses to high-fidelity patient simulation SO ACADEMIC MEDICINE LA English DT Article AB Purpose. To understand the responses of medical students and educators to high-fidelity patient simulation, a new technology allowing "practice without risk." Method. Pilot groups of students (n = 27) and educators (n = 33) were exposed to a simulator session, then surveyed with multiple-choice and open-ended questions. Open-ended comments were transcribed and coded. They were analyzed for recurring themes and tested for interrater agreement. An independent focus group subsequently performed higher-level thematic analysis. Results. Overall, 85% of the students rated the session excellent and 85% of the educators rated it excellent or very good. Over 80% of both groups thought that simulator-based training should be required for all medical students. Analytic categories derived from written comments were: Overall Assessment (i.e., "generally good experience"); Process Descriptors (i.e., "very realistic"); Teaching Utility (i.e., "broad educational tool"); Pedagogic Efficacy (i.e., "promotes critical thinking"); and Goals for Future Use (i.e., "more practice sessions"). Thirty percent of students and 38% of educators were impressed by the realism of the simulator, and they (37% and 25%, respectively) identified the ability to "practice" medicine as the primary advantage of simulation The focus group rated cost as the major current disadvantage (66%). Conclusions. Students' and educators' responses to high-fidelity patient simulation were very positive. The ability to practice without risk must be weighed against the cost of this new technology. C1 Partners HealthCare Syst, Ctr Med Simulat, Boston, MA USA. Harvard Univ, Macy Inst, Boston, MA 02115 USA. Univ Michigan, Hlth Syst, Med Readiness Trainer Team, Dept Emergency Med,Med Educ Scholars Program, Ann Arbor, MI 48109 USA. Harvard Univ, Grad Sch Educ, Technol Educ Program, Cambridge, MA 02138 USA. Ctr Integrat Med & Innovat Technol, Boston, MA USA. RP Gordon, JA (reprint author), Harvard Univ, Sch Med, Dept Emergency Med, Massachusetts Gen Hosp,Div Emergency Med, 55 Fruit St,CLN 115, Boston, MA 02114 USA. NR 10 TC 145 Z9 147 U1 1 U2 11 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 MAY PY 2001 VL 76 IS 5 BP 469 EP 472 DI 10.1097/00001888-200105000-00019 PG 4 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 430JU UT WOS:000168571400016 PM 11346525 ER PT J AU Peters, AS Feins, A Rubin, R Seward, S Schnaidt, K Fletcher, RH AF Peters, AS Feins, A Rubin, R Seward, S Schnaidt, K Fletcher, RH TI The longitudinal primary care clerkship at Harvard Medical School SO ACADEMIC MEDICINE LA English DT Article AB The primary care clerkship (PCC) at Harvard medical School was established in 1997, The goals are to provide students with longitudinal experiences with patients and to include modem themes in the curriculum: managing illness and clinical relationships over time; finding the best available answers to clinical questions; preventing illness and promoting health; dealing with clinical uncertainty; getting the best outcomes with available resources; working in a health care team; and sharing decision making with patients. The PCC, a required course in the clinical years, meets one afternoon a week for nine months, Students spend three afternoons per month in primary care practices, where they see three to five patients per session and follow at least one patient ("longitudinal patient") over time. Classroom sessions, in both large- and small-group formats, promote a common educational philosophy and experience, and reinforce habits of problem-based learning established in the preclinical years, The students rated 74% of their preceptors excellent, especially praising their ability to facilitate and support good interpersonal relationships with patients, their ability to encourage students' independent evaluation of patients (as opposed to shadowing) and their enthusiasm for teaching, Students san their longitudinal patients a mean of 4.8 times; 83% saw their patients at least three times, The PCC complements the curriculum of block clerkships in hospitals, and because the two are offered concurrently, students are required to come to terms with two substantially different cultures within medicine, Other medical schools are beginning to develop longitudinal clerkships to ensure that students have essential educational experiences that are difficult to achieve in block, hospital-based clerkships. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Peters, AS (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 126 Brookline Ave,Suite 201, Boston, MA 02215 USA. NR 10 TC 16 Z9 18 U1 1 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 MAY PY 2001 VL 76 IS 5 BP 484 EP 488 DI 10.1097/00001888-200105000-00023 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 430JU UT WOS:000168571400020 PM 11346529 ER PT J AU Chou, C AF Chou, C TI Case-based teaching of perioperative medicine SO ACADEMIC MEDICINE LA English DT Article C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Chou, C (reprint author), San Francisco Vet Affairs Med Ctr, 4150 Clement St 111, San Francisco, CA 94121 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 MAY PY 2001 VL 76 IS 5 BP 558 EP 559 DI 10.1097/00001888-200105000-00105 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 430JU UT WOS:000168571400102 PM 11346611 ER PT J AU Chou, C Jain, S Glick, S AF Chou, C Jain, S Glick, S TI A curriculum to teach residents to teach in the ambulatory setting SO ACADEMIC MEDICINE LA English DT Article C1 Univ Calif San Francisco, VA PRIME Program, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Cook Cty Hosp, Chicago, IL 60612 USA. RP Chou, C (reprint author), Univ Calif San Francisco, VA PRIME Program, San Francisco Vet Affairs Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2001 VL 76 IS 5 BP 571 EP 571 DI 10.1097/00001888-200105000-00122 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 430JU UT WOS:000168571400119 PM 11346629 ER PT J AU Wagenaar, DJ Weissleder, R Hengerer, A AF Wagenaar, DJ Weissleder, R Hengerer, A TI Glossary of molecular imaging terminology SO ACADEMIC RADIOLOGY LA English DT Article C1 Siemens Med Syst, Nucl Med Grp, Hoffman Estates, IL 60195 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Siemens Med Solut, Basic Res & Dev, Erlangen, Germany. RP Wagenaar, DJ (reprint author), Siemens Med Syst, Nucl Med Grp, 2501 N Barrington Rd, Hoffman Estates, IL 60195 USA. NR 0 TC 20 Z9 23 U1 0 U2 3 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAY PY 2001 VL 8 IS 5 BP 409 EP 420 DI 10.1016/S1076-6332(03)80549-4 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 427EE UT WOS:000168391200007 PM 11345272 ER PT J AU Zhukareva, V Newell, KL Lee, VMY Trojanowski, JQ AF Zhukareva, V Newell, KL Lee, VMY Trojanowski, JQ TI Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer's disease SO ACTA NEUROPATHOLOGICA LA English DT Article DE tauopathies; traumatic brain injury; punch drunk syndrome ID TRAUMATIC BRAIN INJURY; AMYLOID PRECURSOR PROTEIN; HEAD-INJURY; AXONAL INJURY; BETA-PROTEIN; DEPOSITION; EPITOPES; SITES AB Insights into mechanisms of familial Alzheimer's disease (AD) caused by genetic mutations have emerged rapidly compared to sporadic AD. Indeed, despite identification of several sporadic AD risk factors, it remains enigmatic how or why they predispose to neurodegenerative disease. For example, traumatic brain injury (TBI) predisposes to AD, and recurrent TBI in career boxers may cause a progressive memory disorder associated with AD-like brain pathology known as dementia pugilistica (DP). Although the reasons for this are unknown, repeated TBI may cause DP by mechanisms similar to those involved in AD. To investigate this possibility, we compared the molecular profile of tau pathologies in DP with those in AD and showed that the same tau epitopes map to filamentous tau inclusions in AD and DP brains, while the abnormal tau proteins isolated from DP brains are indistinguishable from the six abnormally phosphorylated brain tau isoforms in AD brains. Thus, these data suggest that recurrent TBI may cause DP by activating pathological mechanisms similar to those that cause brain degeneration due to accumulations of filamentous tau lesions in AD, and similar, albeit attenuated, activation of these processes by a single TBI may increase susceptibility to sporadic AD decades after the event. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Trojanowski, JQ (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Ctr Neurodegenerat Dis Res, 3rd Floor HUP,Maloney Bldg,3600 Spruce St, Philadelphia, PA 19104 USA. NR 32 TC 1 Z9 1 U1 0 U2 6 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 MAY PY 2001 VL 101 IS 5 BP 518 EP 524 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 446UU UT WOS:000169533200013 ER PT J AU Barnett, PG Rodgers, JH Bloch, DA AF Barnett, PG Rodgers, JH Bloch, DA TI A meta-analysis comparing buprenorphine to methadone for treatment of opiate dependence SO ADDICTION LA English DT Article ID OPIOID DEPENDENCE; MAINTENANCE TREATMENT; HEROIN-ADDICTS; CONTROLLED TRIAL; ABUSE AB Background. The unique pharmacological properties of buprenorphine may make it a useful maintenance therapy for opiate addiction. This meta-analysis considers the effectiveness of buprenorphine relative to methadone. Methods. A systematic literature search identified five randomized clinical trials comparing buprenorphine to methadone. Data from these trials were obtained. Retention in treatment was analyzed with a Cox proportional hazards regression. Urinalyses for opiates were studied with analysis of variance and a common method of handling missing values. A meta-analysis was used to combine these results. Results. Subjects who received 8-12 mg/day buprenorphine had 1.26 times the relative risk of discontinuing treatment (95% confidence interval 1.01-1.57) and 8.3% more positive urinalyses (95% confidence interval 2.7-14%) than subjects receiving 50-80 mg/day methadone. Buprenophrine was more effective than 20-35 mg/day methadone. There was substantial variation in outcomes in the different trials. Conclusions. The variation between trials may be due to differences in dose levels, patient exclusion criteria and provision of psychosocial treatment. The difference in the effectiveness of buprenorphine and methadone may be statistically significant, but the differences are small compared to the wide variance in outcomes achieved in different methadone treatment programs. Further research is needed to determine if buprenorphine treatment is more effective than methadone in particular settings or in particular subgroups of patients. C1 US Dept Vet Affairs, Cooperat Studies Program, VA Palo Alto Hlth Care Syst, Menlo Park, CA 94025 USA. US Dept Vet Affairs, Hlth Econ Resource Ctr, VA Palo Alto Hlth Care Syst, Menlo Park, CA 94025 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. RP Barnett, PG (reprint author), US Dept Vet Affairs, Cooperat Studies Program, VA Palo Alto Hlth Care Syst, 795 Willow Rd,152 MPD, Menlo Park, CA 94025 USA. FU NIDA NIH HHS [1-Y01-DA-40032] NR 22 TC 95 Z9 95 U1 1 U2 8 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAY PY 2001 VL 96 IS 5 BP 683 EP 690 DI 10.1046/j.1360-0443.2001.9656834.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 425VR UT WOS:000168312800004 PM 11331027 ER PT J AU Crabb, DW Pinairs, J Hasanadka, R Fang, M Leo, MA Lieber, CS Tsukamoto, H Motomura, K Miyahara, T Ohata, M Bosron, W Sanghani, S Kedishvili, N Shiraishi, H Yokoyama, H Miyagi, M Ishii, H Bergheim, I Menzl, I Parlesak, A Bode, C AF Crabb, DW Pinairs, J Hasanadka, R Fang, M Leo, MA Lieber, CS Tsukamoto, H Motomura, K Miyahara, T Ohata, M Bosron, W Sanghani, S Kedishvili, N Shiraishi, H Yokoyama, H Miyagi, M Ishii, H Bergheim, I Menzl, I Parlesak, A Bode, C TI Alcohol and retinoids SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Japanese-Medical-Society-of-Alcohol-and-Drug-Studie/10th International-Society-for-Biomedical-Research-on-Alcoholism CY JUL 02-08, 2000 CL YOKOHAMA, JAPAN SP Japanese Med Soc Alcohol & Drug Studies, Int Soc Biomed Res Alcoholism DE retinoic acid; retinoid receptors; vitamin A; beta-carotene; hepatic stellate cells; aldehyde dehydrogenases; alcohol dehydrogenases ID HEPATIC VITAMIN-A; ALDEHYDE DEHYDROGENASE-2 PROMOTER; CHRONIC ETHANOL-CONSUMPTION; CAROTENE CANCER PREVENTION; CHRONIC HYPERVITAMINOSIS-A; ITO CELL-PROLIFERATION; BETA-CAROTENE; LIVER-DISEASE; ALPHA-TOCOPHEROL; BINDING-PROTEINS AB This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hirokazu Yokoyama and David Crabb. The presentations were (1) Roles of vitamin A, retinoic acid, and retinoid receptors in the expression of liver ALDH2, by J. Pinaire, R. Hasanadka, M. Fang, and David W. Crabb; (2) Alcohol, vitamin A, and p-carotene: Adverse interactions, by M. A. Leo and Charles S. Lieber; (3) Retinoic acid, hepatic stellate cells, and Kupffer cells, by Hidekazu Tsukamoto, K, Motomura, T. Miyahara, and M. Ohata; (4) Retinoid storage and metabolism in liver, by William Bosron, S. Sanghani, and N. Kedishvili; (5) Characterization of oxidation pathway from retinol to retinoic acid in esophageal mucosa, by Haruko Shiraishi, Hirokazu Yokoyama, Michiko Miyagi, and Hiromasa Ishii; and (6) Ethanol in an inhibitor of the cytosolic oxidation of retinol in the liver and the large intestine of rats as well as in the human colon mucosa, by Ina Bergheim, Ina Menzl, Alexandr Parlesak, and Christiane Bode. C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Mt Sinai Med Ctr, Alcohol Res Ctr, New York, NY 10029 USA. Bronx VA Med Ctr, Alcohol Res Ctr, New York, NY 10029 USA. Univ So Calif, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90089 USA. Sepulveda VA Med Ctr, VA Greater Los Angeles HealthCare Syst, Sepulveda, CA USA. Univ Missouri, Kansas City, MO 64110 USA. Keio Univ, Dept Internal Med, Tokyo, Japan. Univ Hohenheim, Dept Physiol Nutr, D-7000 Stuttgart, Germany. RP Crabb, DW (reprint author), Indiana Univ, Sch Med, Dept Med, 545 Barnhill Dr,Emerson 317, Indianapolis, IN 46202 USA. RI Parlesak, Alexandr/K-6310-2013 OI Parlesak, Alexandr/0000-0002-8973-3467 NR 94 TC 24 Z9 24 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2001 VL 25 IS 5 SU 1 BP 207S EP 217S DI 10.1111/j.1530-0277.2001.tb02398.x PG 11 WC Substance Abuse SC Substance Abuse GA 434ZP UT WOS:000168846000034 PM 11391073 ER PT J AU Haber, P Nakamura, M Tsuchimoto, K Ishii, H Keogh, GW Apte, MV Moran, CS Stewart, NL Crawford, DHG Pirola, RC McCaughan, GW Ramm, GA Wilson, JS Nishino, H Kohno, M Aizawa, R Tajima, N Maruyama, K Takahashi, H Matsushita, S Okuyama, K Yokoyama, A Nakamura, Y Shirakura, K Ishii, H Conigrave, KM Hu, BF Camargo, CA Stampfer, MJ Willett, WC Rimm, EB AF Haber, P Nakamura, M Tsuchimoto, K Ishii, H Keogh, GW Apte, MV Moran, CS Stewart, NL Crawford, DHG Pirola, RC McCaughan, GW Ramm, GA Wilson, JS Nishino, H Kohno, M Aizawa, R Tajima, N Maruyama, K Takahashi, H Matsushita, S Okuyama, K Yokoyama, A Nakamura, Y Shirakura, K Ishii, H Conigrave, KM Hu, BF Camargo, CA Stampfer, MJ Willett, WC Rimm, EB TI Alcohol and the pancreas SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Japanese-Medical-Society-of-Alcohol-and-Drug-Studie/10th International-Society-for-Biomedical-Research-on-Alcoholism CY JUL 02-08, 2000 CL YOKOHAMA, JAPAN SP Japanese Med Soc Alcohol & Drug Studies, Int Soc Biomed Res Alcoholism DE ethanol-induced pancreatic injury; pancreatic stellate cells; pancreatic enzyme secretion; type 2 diabetes ID INSULIN SENSITIVITY; STELLATE CELLS; DIABETES-MELLITUS; RISK-FACTORS; ETHANOL; MEN; CONSUMPTION; POLYMORPHISMS; FIBROGENESIS; HYPOGLYCEMIA AB This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama, Japan. The presentations were (1) Phenotypic alteration of myofibroblast during ethanol-induced pancreatic injury: its relation to bFGF, by Masahiko Nakamura, Kanji Tsuchimoto, and Hiromasa Ishii; (2) Activation of pancreatic stellate: cells in pancreatic fibrosis, by Paul S. Haber, Gregory W. Keogh, Minoti V. Apte, Corey S. Moran, Nancy L. Stewart, Darrell H.G. Crawford, Romano C. Pirola, Geoffrey W. McCaughan, Grant A. Ramm, and Jeremy S. Wilson; (3) Pancreatic blood flow and pancreatic enzyme secretion on acute ethanol infusion in anesthetized RAT, by H. Nishino, M. Kohno, R. Aizawa, and N. Tajima; (4) Genotype difference of alcohol-metabolizing enzymes in relation to chronic alcoholic pancreatitis between the alcoholic in the National Institute on Alcoholism and patients in other general hospitals in Japan, by K. Maruyama, II. Takahashi, S. Matsushita, K. Okuyama, A. Yokoyama, Y. Nakamura, K. Shirakura, and H. Ishii; and (5) Alcohol consumption and incidence of type 2 diabetes, by Katherine M. Conigrave, B. Frank Hu, Carlos A. Camargo Jr, Meir J. Stampfer, Waiter C. Willett, and Eric B. Rimm. C1 Royal Prince Alfred Hosp, Drug & Alcohol Dept, Camperdown, NSW 2050, Australia. Prince Wales Hosp, Dept Gastroenterol, Pancreat Res Grp, Sydney, NSW, Australia. Prince Wales Hosp, Dept Surg, Sydney, NSW, Australia. Univ New S Wales, Sydney, NSW, Australia. Queensland Inst Med Res, Clin Sci Unit, Hepat Fibrosis Grp, Brisbane, Qld 4006, Australia. Kitasato Inst, Ctr Basic Res, Tokyo, Japan. Kitasato Inst Hosp, Tokyo, Japan. Keio Univ, Sch Med, Dept Internal Med, Tokyo, Japan. Jijei Univ, Sch Med, Dept Internal Med 3, Tokyo, Japan. Kurihama Natl Hosp, Natl Inst Alcoholism, Kanagawa, Japan. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. Royal Prince Alfred Hosp, Durg & Alcohol Dept, Camperdown, NSW 2050, Australia. Univ Sydney, Dept Med, Sydney, NSW 2006, Australia. Univ Sydney, Dept Publ Hlth & Commun Med, Sydney, NSW 2006, Australia. Univ Sydney, Dept Psychol Med, Sydney, NSW 2006, Australia. RP Haber, P (reprint author), Royal Prince Alfred Hosp, Drug & Alcohol Dept, Missenden Rd, Camperdown, NSW 2050, Australia. RI Crawford, Darrell/F-2157-2010; Apte, Minoti/F-3063-2010; Ramm, Grant/G-2669-2013; Wilson, Jeremy/I-4586-2013 OI Wilson, Jeremy/0000-0003-2355-8632 NR 39 TC 12 Z9 13 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2001 VL 25 IS 5 SU 1 BP 244S EP 250S DI 10.1111/j.1530-0277.2001.tb02403.x PG 7 WC Substance Abuse SC Substance Abuse GA 434ZP UT WOS:000168846000039 PM 11391078 ER PT J AU Hall, PDM Lieber, CS DeCarli, LM French, SW Lindros, KO Jarvelainen, H Bode, C Parlesak, A Bode, JC AF Hall, PDM Lieber, CS DeCarli, LM French, SW Lindros, KO Jarvelainen, H Bode, C Parlesak, A Bode, JC TI Models of alcoholic liver disease in rodents: A critical evaluation SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Japanese-Medical-Society-of-Alcohol-and-Drug-Studie/10th International-Society-for-Biomedical-Research-on-Alcoholism CY JUL 02-08, 2000 CL YOKOHAMA, JAPAN SP Japanese Med Soc Alcohol & Drug Studies, Int Soc Biomed Res Alcoholism DE alcoholic liver disease; alcoholic liver injury; rat diet; endotoxin-ethanol interactions; jejunoileal bypass ID JEJUNOILEAL-BYPASS; DIETARY-FAT; RAT-LIVER; VITAMIN-A; ITO CELL; ETHANOL; CIRRHOSIS; FIBROSIS; METABOLISM; NECROSIS AB This article represents the proceedings of a workshop at the 2000 ISBRA Meeting in Yokohama. Japan. The chairs were J. Christian Bode and Hiroshi Fukui. The presentations were (1) Essentials and the course of the pathological spectrum of alcoholic liver disease in humans, by P. de la M. nail; (2) Lieber-DeCarli liquid diet for alcohol-induced liver injury in rats, by C. S. Lieber and L. M. DeCarli; (3) Tsukamoto-French model of alcoholic liver injury, by S. W. French; (4) Animal models to study endotoxin-ethanol interactions. by K. O. Lindros and H. Jarvelainen; and (5) Jejunoileal bypass operation in rats-A model for alcohol-induced liver injury? by Christiane Bode, Alexandr Parlesak, and J. Christian Bode. C1 Univ Cape Town, Dept Anat Pathol, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. Robert Bosch Krankenhaus, Dept Internal Med, Stuttgart, Germany. Nara Med Univ, Dept Internal Med 3, Kashihara, Nara 634, Japan. Bronx Vet Affairs Med Ctr, New York, NY USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Pathol, Torrance, CA 90509 USA. Natl Publ Hlth Inst, Alcohol Res Ctr, Helsinki, Finland. Univ Hohenheim, Dept Physiol Nutr, D-7000 Stuttgart, Germany. RP Hall, PDM (reprint author), Univ Cape Town, Dept Anat Pathol, Fac Hlth Sci, Room 144,Falmouth Bldg,Anzio Rd, ZA-7925 Cape Town, South Africa. RI Parlesak, Alexandr/K-6310-2013 OI Parlesak, Alexandr/0000-0002-8973-3467 NR 59 TC 31 Z9 32 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAY PY 2001 VL 25 IS 5 SU 1 BP 254S EP 261S DI 10.1111/j.1530-0277.2001.tb02405.x PG 8 WC Substance Abuse SC Substance Abuse GA 434ZP UT WOS:000168846000041 ER PT J AU Kahn, JA Parsons, SK Pizzo, PA Newburger, JW Homer, CJ AF Kahn, JA Parsons, SK Pizzo, PA Newburger, JW Homer, CJ TI Work-family issues and perceptions of stress among pediatric faculty and house staff SO AMBULATORY PEDIATRICS LA English DT Article DE pediatric; stress; work-family ID OCCUPATIONAL STRESS; WOMEN; CAREER; PHYSICIANS; MEDICINE; ILLNESS AB Objectives.-To examine work-family balance issues and predictors of stress related to work-family balance among pediatric house staff and faculty. Methods.-Data were. obtained through an anonymous mail survey. Univariate analyses assessed associations between work-family issues (work-related factors that affect work-family balance, perceived support, work-family-related stress, and proposed solutions) and the following variables: gender, parental status, working status of spouse, and academic rank. Multiple linear regression examined independent predictors of perceived stress. Results.-Fifty percent of the 327 respondents cared for dependent children, and 20% expected to care for an elderly person in the next 5 years. Only 5% strongly agreed that their division or department was concerned about supporting members' work-family balance, and 4% strongly agreed that existing programs supported their needs. Eighty-three percent reported feeling stressed as a result of efforts to balance work and family. Independent predictors of stress included perceived need to choose between career and family, increasing age, dependent children, less support from colleagues and supervisors, and female gender. Conclusions.-Work-family balance issues are responsible for substantial perceived stress. Academic departments should consider a commitment to supporting faculty who are struggling with these issues, including creation of work-family policies and programs, development of mentoring systems, and reexamination of existing expectations for work practices. C1 Childrens Hosp, Med Ctr, Div Adolescent Med, Cincinnati, OH 45229 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. RP Kahn, JA (reprint author), Childrens Hosp, Med Ctr, Div Adolescent Med, 3333 Burnet Ave, Cincinnati, OH 45229 USA. NR 37 TC 8 Z9 8 U1 2 U2 3 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 MAY-JUN PY 2001 VL 1 IS 3 BP 141 EP 149 DI 10.1367/1539-4409(2001)001<0141:WFIAPO>2.0.CO;2 PG 9 WC Pediatrics SC Pediatrics GA 473YJ UT WOS:000171076700005 PM 11888391 ER PT J AU Giugliano, RP McCabe, CH Antman, EM Cannon, CP Van de Werf, F Wilcox, RG Braunwald, E AF Giugliano, RP McCabe, CH Antman, EM Cannon, CP Van de Werf, F Wilcox, RG Braunwald, E CA Thrombolysis Myocardial Infarction TI Lower-dose heparin with fibrinolysis is associated with lower rates of intracranial hemorrhage SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; TISSUE-PLASMINOGEN-ACTIVATOR; PRACTICE GUIDELINES COMMITTEE; PARTIAL THROMBOPLASTIN TIME; EARLY INTRAVENOUS HEPARIN; GUSTO-I TRIAL; THROMBOLYTIC THERAPY; CORONARY THROMBOLYSIS; INTRACEREBRAL HEMORRHAGE; THROMBIN INHIBITION AB Background The optimal heparin dose as an adjunct to fibrinolysis and its role in causing intracranial hemorrhage (ICH) is unclear. Methods We reviewed the heparin regimens and rates of ICH in 3 sets of recent fibrinolytic trials: (1) studies with accelerated recombinant tissue plasminogen activator (TPA, alteplase) plus intravenous heparin, in which the heparin regimen was changed during the course of the trial; (2) phase III trials with accelerated TPA plus intravenous heparin; and (3) trials of new single-bolus fibrinolytic agents. Results lower rates of ICH were observed among studies of accelerated TPA that reduced the heparin dose mid-trial (TIMI 9A --> 9B: 1.87% --> 1.07%, GUSTO-IIa --> IIb: 0.92% --> 0.71%, TIMI 10B: 2.80% --> 1.16%). Rates of ICH with accelerated TPA gradually increased from GUSTO-I (0.72%) in 1990 to 1993 to ASSENT-2 (0.94%) in 1997 to 1998. However, this trend was reversed in InTIME-II, which used the lowest heparin dose and most aggressive activated partial thromboplastin time monitoring and observed an ICH rate of 0.64% with accelerated TPA. lower ICH rates were also observed when the heparin dose was reduced with single-bolus tenecteplase (TNK-TPA) and lanoteplase. Conclusions Nonrandomized comparisons with accelerated TPA suggest that lower doses of intravenous heparin are associated with lower rates of ICH. This observation also appears to apply to single-bolus TNK-TPA and novel plasminogen activator. A lower-dose, weight-adjusted heparin regimen (60 U/kg bolus; maximum, 4000 U; 12 U/kg per hour infusion; maximum, 1000 U/h) with earlier monitoring of activated partial thromboplastin time is currently recommended in the revised American College of Cardiology/American Heart Association myocardial infarction guidelines and should be used in clinical practice. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp,TIMI Study Off, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium. Univ Nottingham Hosp, Dept Cardiovasc Med, Nottingham NG7 2UH, England. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp,TIMI Study Off, 333 Longwood Ave, Boston, MA 02115 USA. NR 52 TC 35 Z9 38 U1 1 U2 4 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 MAY PY 2001 VL 141 IS 5 BP 742 EP 750 DI 10.1067/mhj.2001.114975 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 427YC UT WOS:000168433500008 PM 11320361 ER PT J AU Grinspoon, S Thomas, L Miller, K Pitts, S Herzog, D Klibanski, A AF Grinspoon, S Thomas, L Miller, K Pitts, S Herzog, D Klibanski, A TI Changes in regional fat redistribution and the effects of estrogen during spontaneous weight gain in women with anorexia nervosa SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID BODY-COMPOSITION; MECHANISMS; POPULATION; PREVALENCE; THERAPY; WAIST AB Background: Anorexia nervosa is a disease of severe acquired undernutrition with a high and increasing prevalence among young women in the United States, Objective: The objective was to investigate the effects of spontaneous outpatient weight recovery and estrogen administration on fat distribution in patients with anorexia nervosa. Design: Twenty-seven amenorrheic women aged 26.6 +/- 1.2 y with anorexia nervosa were identified through an outpatient study of bone loss and were randomly assigned to receive or not receive estrogen without any dietary intervention other than calcium and multivitamin supplements. Body composition was measured at baseline and at 6 and 9 mo and was compared with cross-sectional values obtained in 20 healthy, eumenorrheic, age-matched (25.4 +/- 0.5 y) control subjects. Results: Twenty of the 27 patients with anorexia aged 27.0 +/- 1.3 y spontaneously gained weight (4.1 +/- 0.9 kg); body mass index (in kg/m(2)) increased from 16.1 +/- 0.3 to 17.5 +/- 0.4, Fat mass and lean mass accounted for 68% and 32% of the gain in total body mass, respectively With spontaneous weight gain, there was a significant increase in the percentage of trunk far from 32.4 +/- 1.3% at baseline to 36.5 +/- 1.0% at 9 mo (P = 0.03), which correlated with urinary free cortisol (r = 0.66, P = 0.003), Estrogen treatment was not protective against the gain in trunk fat with spontaneous weight gain. Conclusions: ln women with anorexia nervosa, spontaneous weight gain is associated with a significant increase in trunk adiposity, and estrogen administration may not protect against the accumulation of central far with weight gain. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [R01-DK52625, P32-DK07028]; NIMH NIH HHS [MH38333] NR 21 TC 63 Z9 66 U1 1 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 2001 VL 73 IS 5 BP 865 EP 869 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 426QM UT WOS:000168359900004 PM 11333838 ER PT J AU Kearney, DJ AF Kearney, DJ TI Retreatment of Helicobacter pylori infection after initial treatment failure SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID RANITIDINE BISMUTH CITRATE; PRETREATMENT ANTIBIOTIC-RESISTANCE; 1-WEEK TRIPLE THERAPIES; PEPTIC-ULCER DISEASE; METRONIDAZOLE RESISTANCE; CLARITHROMYCIN RESISTANCE; ERADICATION THERAPY; CLINICAL RELEVANCE; TREATMENT REGIMENS; QUADRUPLE THERAPY AB OBJECTIVES: Helicobacter pylori treatment regimens fail to cure the infection in at least 10-20% of patients undergoing initial treatment. Retreatment strategies for patients who have failed initial treatment for H. pylori infection remain poorly described. METHODS: The literature describing the Frequency of H. pylori treatment failure and factors leading to failure is reviewed. The role of antibiotic resistance is discussed and clinical studies assessing success rates according to antibiotic resistance are described. Clinical trials evaluating the treatment success rates for a second episode of treatment are discussed. RESULTS: The literature describing retreatment of failed H. pylori infection remains limited. The existing data support the use of bismuth-based quadruple therapy or ranitidine bismuth citrate (RBC)-based triple therapy as the preferred agents after initial treatment failure. CONCLUSION: Further studies are needed to better define the optimal second treatment regimen after failed H. pylori treatment. (C) 2001 by Am. Cell. of Gastroenterology. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA USA. RP Kearney, DJ (reprint author), VAMC, 111GI,1660 S Columbian Way, Seattle, WA 98108 USA. NR 65 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2001 VL 96 IS 5 BP 1335 EP 1339 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 430WW UT WOS:000168599300011 PM 11374665 ER PT J AU Dore, MP Sepulveda, AR El-Zimaity, H Yamaoka, Y Osato, MS Mototsugu, K Nieddu, AM Realdi, G Graham, DY AF Dore, MP Sepulveda, AR El-Zimaity, H Yamaoka, Y Osato, MS Mototsugu, K Nieddu, AM Realdi, G Graham, DY TI Isolation of Helicobacter pylori from sheep - Implications for transmission to humans SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROSPIRILLUM-HOMINIS; CAMPYLOBACTER-PYLORI; ABATTOIR WORKERS; INFECTION; SUSCEPTIBILITY; GASTRITIS; SURVIVAL; ANIMALS; STAIN; FOOD AB OBJECTIVES: When and how Helicobacter pylori (H. pylori) originally entered the human population as well as how the infection is transmitted in different communities is unknown. We previously showed that Sardinian shepherds had almost a 100% prevalence of H. pylori and that the prevalence was higher than that of their same-household siblings. AIM: To examine whether H. pylori infection might be transmitted from sheep. METHODS: Milk and gastric tissue were cultured and analyzed by PCR amplification using three sets of primers Helicobacter genus-specific 16S rRNA and two sets of primers specific for H. pylori vacA gene. RESULTS: Helicobacter DNA was demonstrated in 60% (38/63) of milk samples and in 30% (6/20) of sheep tissue samples. H. pylori vacA gene was amplified in five of 38 milk samples, and in two of six sheep tissue samples respectively. H. pylori were cultured from sheep milk and tissue samples and confirmed as H. pylori on the basis of colony morphology, positive biochemical reactions, and negative Gram stain. Sequence analysis of 16S rRNA PCR products from these isolates demonstrated 99% identity with H. pylori. CONCLUSIONS: Together, the presence of Il. pylori in sheep stomach in the absence of associated gastritis and recovery of H. pylori from sheep milk and gastric tissue suggest that sheep may be a natural host for Il. pylori. (C) 2001 by Am. Cell. of Gastroenterology. C1 Univ Sassari, Ist Clin Med, Dept Internal Med, I-07100 Sassari, Italy. Univ Sassari, Inst Veterinarian Pathol Anat, I-07100 Sassari, Italy. VA Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Dore, MP (reprint author), Univ Sassari, Ist Clin Med, Dept Internal Med, Viale San Pietro 8, I-07100 Sassari, Italy. NR 31 TC 61 Z9 69 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2001 VL 96 IS 5 BP 1396 EP 1401 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 430WW UT WOS:000168599300020 PM 11374673 ER PT J AU Applebaum-Shapiro, SE Peters, JA O'Connell, JA Aston, CE Whitcomb, DC AF Applebaum-Shapiro, SE Peters, JA O'Connell, JA Aston, CE Whitcomb, DC TI Motivations and concerns of patients with access to genetic testing for hereditary pancreatitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CATIONIC TRYPSINOGEN GENE; BREAST-CANCER; MUTATIONS; SUSCEPTIBILITY; HETEROGENEITY; WOMEN; MAPS; RISK AB OBJECTIVES: Direct DNA testing is now available for hereditary pancreatitis (HP). This study aimed to identify the factors that motivated individuals to participate in research and to determine how research participants used their genetic test results. METHODS: A survey was mailed to 247 participants (110 male, 137 female) who were greater than or equal to 18 yr of age and living in the US. Data analysis was primarily a description of frequency distribution of the responses. RESULTS: Ninety-one of 247 participants (37%) completed the survey. Of the 55 female and 36 male respondents, 60% were 31-55 yr old, and a total of 54% tested positive for HP. The most common reason for participating in research was "to help a relative/family member" (61%), and genetic testing was pursued because of "the disturbance of seeing affected relatives" (48%) and "the desire to help future generations" (33%). Perceived risk of developing HP in the future was the least important motivating factor in seeking genetic testing. Sixty-two percent of respondents had received their genetic test results. All but one chose to share their results with at least one person: most often with family members (96%) and physicians (62%), and least often with insurance companies (4%). The most common influential factor in withholding information was "the fear of insurance discrimination" (23%). CONCLUSIONS: The major motivations to participate in the HP genetic research study were to obtain genetic testing and to help current family members and future generations. The major concern was insurance discrimination. Participants clearly appreciate the availability of genetic testing for HP. These results suggest that a mechanism to disclose results to research participants should be considered, and effective ways to protect at-risk individuals from insurance discrimination must remain a genetics health care priority. (C) 2001 by Am. Cell. of Gastroenterology. C1 Univ Pittsburgh, Dept Med GI, Ctr Genom Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Physiol & Cell Biol, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Applebaum-Shapiro, SE (reprint author), Univ Pittsburgh, Dept Med GI, Ctr Genom Sci, 3550 Terrace St,560A Scaife Hall, Pittsburgh, PA 15261 USA. FU NIDDK NIH HHS [DK51954, DK54709] NR 34 TC 23 Z9 23 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 2001 VL 96 IS 5 BP 1610 EP 1617 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 430WW UT WOS:000168599300055 PM 11374708 ER PT J AU Bastepe, M Lane, AH Yuppner, H AF Bastepe, M Lane, AH Yuppner, H TI Paternal uniparental isodisomy of chromosome 20q - and the resulting changes in GNAS1 methylation - as a plausible cause of pseudohypoparathyroidism SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GS-ALPHA GENE; HEREDITARY OSTEODYSTROPHY; LOCUS; IB; NEURONATIN; TRANSCRIPT; ANTISENSE; PROTEINS; CLUSTER; HORMONE AB Heterozygous inactivating mutations in the GNAS1 exons (20q13.3) that encode the alpha -subunit of the stimulatory G protein (Gs alpha) are found in patients with pseudohypoparathyroidism type Ia (PHP-Ia) and in patients with pseudopseudohypoparathyroidism (pPHP). However, because of paternal imprinting, resistance to parathyroid hormone (PTH)-and, sometimes, to other hormones that require Gs alpha signaling-develops only if the defect is inherited from a female carrier of the disease gene. An identical mode of inheritance is observed in kindreds with pseudohypoparathyroidism type Ib (PHP-Ib), which is most likely caused by mutations in regulatory regions of the maternal GNAS1 gene that are predicted to interfere with the parent-specific methylation of this gene. We report a patient with PTH-resistant hypocalcemia and hyperphosphatemia but without evidence for Albright hereditary osteodystrophy who has paternal uniparental isodisomy of chromosome 20q and lacks the maternal-specific methylation pattern within GNAS1. Since studies in the patient's fibroblasts did not reveal any evidence of impaired Gs alpha protein or activity, it appears that the loss of the maternal GNAS1 gene and the resulting epigenetic changes alone can lead to PTH resistance in the proximal renal tubules and thus lead to impaired regulation of mineral-ion homeostasis. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. SUNY Stony Brook, Stony Brook Sch Med, Dept Pediat, Div Pediat Endocrinol, Stony Brook, NY 11794 USA. RP Yuppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Wellman 5, Boston, MA 02114 USA. FU PHS HHS [R01 46718-06] NR 26 TC 115 Z9 120 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2001 VL 68 IS 5 BP 1283 EP 1289 DI 10.1086/320117 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 423HZ UT WOS:000168171200022 PM 11294659 ER PT J AU Dryja, TP Adams, SM Grimsby, JL McGee, TL Hong, DH Li, TS Andreasson, S Berson, EL AF Dryja, TP Adams, SM Grimsby, JL McGee, TL Hong, DH Li, TS Andreasson, S Berson, EL TI Null RPGRIP1 alleles in patients with Leber congenital amaurosis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PIGMENTOSA GTPASE REGULATOR; LINKED RETINITIS-PIGMENTOSA; NUCLEOTIDE-EXCHANGE FACTOR; GENE; MUTATIONS; CRX; HOMOLOGY; RCC1 AB We isolated and characterized the entire coding sequence of a human gene encoding a protein that interacts with RPGR, a protein that is absent or mutant in many cases of X-linked retinitis pigmentosa. The newly identified gene, called "RPGRIP1" for RPGR-interacting protein (MIM 605446), is located within 14q11, and it encodes a protein predicted to contain 1, 259 amino acids. Previously published work showed that both proteins, RPGR and RPGRIP1, are present in the ciliary structure that connects the inner and outer segments of rod and cone photoreceptors. We surveyed 57 unrelated patients who had Leber congenital amaurosis for mutations in RPGRIP1 and found recessive mutations involving both RPGRIP1 alleles in 3 (6%) patients. The mutations all create premature termination codons and are likely to be null alleles. Patients with RPGRIP1 mutations have a degeneration of both rod and cone photoreceptors, and, early in life, they experience a severe loss of central acuity, which leads to nystagmus. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Univ Lund Hosp, Dept Ophthalmol, S-22185 Lund, Sweden. RP Dryja, TP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY00169, EY08683, R01 EY000169, R01 EY008683, R37 EY000169] NR 19 TC 180 Z9 181 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 2001 VL 68 IS 5 BP 1295 EP 1298 DI 10.1086/320113 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 423HZ UT WOS:000168171200024 PM 11283794 ER PT J AU Hauser, R Eisen, EA Pothier, L Christiani, DC AF Hauser, R Eisen, EA Pothier, L Christiani, DC TI A prospective study of lung function among boilermaker construction workers exposed to combustion particulates SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE boilermakers; lung function; combustion particulates; welding; occupational health; respiratory diseases; natural gas ID FUEL-OIL ASH; SPIROMETRIC VALUES; FLY-ASH; COAL; FLOW AB Background Given the evidence of both acute cross-shift and short-term decrements in lung function in boilermaker construction workers following occupational exposure to combustion particulates, we sought to determine whether exposure is associated with an annual loss in lung function. Methods As part of an ongoing investigation, we conducted a 2-year longitudinal study of lung function among 118 boilermakers. Exposure was assessed with a work history questionnaire. Spirometry measurements were performed annually. Results We found an association between annual FEV1 and hours worked at a gas-fired plant during the previous year, beta = -9.8 mls/100 hours worked (85% CI:-16.0,-3.5) after adjustment for age, baseline FEV1 and cigarette smoking status. The adjusted association between FEV1 and "ever" worked at a gas-fired plant was -99.7 mls (95% CI: -154.8, -44.5). There was also evidence of a negative association between FEV1 and "ever" worked and hours worked at oil and coal-fired plants. Conclusions These data suggest an association between annual lung function loss and working at gas, coal and oil-fired plants. Further follow-up of this cohort of boilermakers is in progress. Am. J. Ind. Med. 39:454-462, 2001. (C) 2001 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Univ Massachusetts, Dept Work Environm, Lowell, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES05497, ES00002]; NIOSH CDC HHS [OH00152] NR 20 TC 13 Z9 13 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 2001 VL 39 IS 5 BP 454 EP 462 DI 10.1002/ajim.1039 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 428FF UT WOS:000168450500002 PM 11333407 ER PT J AU Tsuji-Hayashi, Y Fitts, SS Takai, I Nakai, S Shinzato, T Miwa, M Green, J Young, BA Hosoya, T Maeda, K Blagg, CR Fukuhara, S AF Tsuji-Hayashi, Y Fitts, SS Takai, I Nakai, S Shinzato, T Miwa, M Green, J Young, BA Hosoya, T Maeda, K Blagg, CR Fukuhara, S TI Health-related quality of life among dialysis patients in Seattle and Aichi SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE quality of life (QOL); 36-item Short Form Health Survey (SF-36); dialysis ID STAGE RENAL-DISEASE; OF-LIFE; FUNCTIONAL HEALTH; SURVIVAL; HEMODIALYSIS; PREDIALYSIS; JAPAN AB We used the 36-item Short-Form Health Survey to compare health-related quality of life (HRQOL) between 104 dialysis patients in Seattle, WA, and 2,178 patients in Aichi, Japan. Compared with Aichi patients, Seattle patients had lower scores on three scales related to physical HRQOL: Physical Functioning (PF; P = 0.03), Role-Physical (RP; P = 0.004), and Vitality (VT; P < 0.001). However, scores related to mental HRQOL were higher for Seattle patients compared with those of Aichi patients, which included scores for Role-Emotional (RE; P = 0.005) and Mental Health (MH; P < 0.001). Scores for Bodily Pain, General Health Perception, and Social Functioning did not differ significantly between the two groups. These differences persisted even after potential confounding factors were controlled for. However, after taking into account national norm data for the United States and Japan, differences in PF and VT disappeared, whereas differences in RP, RE, and MH persisted. These results suggest that the higher scores for PF and VT in Aichi patients were partly explained by the higher physical HRQOL of the Japanese general population. Although these data may not be representative of the total dialysis populations in the United States and Japan, they suggest potential differences in HRQOL between patients in the two countries. Additional research is needed to confirm these results and understand the factors associated with these differences. The findings suggest the need for further attention to the physical limitations of US dialysis patients and the mental health of Japanese dialysis patients. (C) 2001 by the National Kidney Foundation, Inc. C1 NW Kidney Ctr, Seattle, WA 98122 USA. Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98195 USA. Univ Tokyo, Grad Sch Med, Tokyo, Japan. Jikei Univ, Dept Hypertens & Nephrol, Tokyo, Japan. Nagoya Univ, Sch Med, Daiko Med Ctr, Dept Internal Med, Nagoya, Aichi 466, Japan. Kyoto Univ, Dept Epidemiol & Outcome Res, Grad Sch Med & Publ Hlth, Kyoto, Japan. RP Tsuji-Hayashi, Y (reprint author), NW Kidney Ctr, 700 Broadway, Seattle, WA 98122 USA. NR 33 TC 8 Z9 9 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAY PY 2001 VL 37 IS 5 BP 987 EP 996 DI 10.1053/ajkd.2001.23639 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 427AW UT WOS:000168383500015 PM 11325681 ER PT J AU Lee, C Fowler, DJ Lemyre, E Sandstrom, MM Holmes, LB Morton, CC AF Lee, C Fowler, DJ Lemyre, E Sandstrom, MM Holmes, LB Morton, CC TI Prenatal diagnosis and molecular cytogenetics in a case of partial trisomy 14 and monosomy 21 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE ventriculomegaly; cleft palate; FISH; haploinsufficiency ID CHROMOSOME-21; DELETION AB We report an unbalanced translocation involving chromosomes 14 and 21 which presented as fetal ventriculomegaly at 33 weeks gestation. Second trimester ultrasound had indicated normal fetal anatomy, including normal intracranial structures. Parental karyotypes showed a paternal balanced translocation: 46,XY,t(14;21)(q12;q21). The unbalanced translocation in the fetus resulted in trisomy for 14pter --> q12 and monosomy for 21pter --> q21. Postnatal examination showed that the male infant had a cleft palate, but no cleft lip, and mild dysmorphic features. Postnatal MRI revealed bilateral and symmetric dilatation of the occipital horns, atria, and temporal horns of the lateral ventricles. Molecular cytogenetic techniques were used to delineate further the breakpoint on chromosome 14 to a site distal of the D14S1071 locus and the breakpoint on chromosome 21 to a region between D21S1918 and D21S1902. More precise definitions of chromosomal breakpoints in such clinical cases should provide more accurate prognosis for individuals with unbalanced karyotypes and assist in the identification of putative developmentally important genes. (C) 2001 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Gynecol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Reprod Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Morton, CC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 1 PY 2001 VL 100 IS 3 BP 246 EP 250 DI 10.1002/1096-8628(20010501)100:3<246::AID-AJMG1254>3.0.CO;2-N PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 423UB UT WOS:000168195200012 PM 11343311 ER PT J AU Steinman, MA Shlipak, MG McPhee, SJ AF Steinman, MA Shlipak, MG McPhee, SJ TI Of principles and pens: Attitudes and practices of medicine housestaff toward pharmaceutical industry promotions SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-General-Internal Medicine CY MAY 05-06, 2000 CL BOSTON, MASSACHUSETTS SP Soc Gen Internal Med ID SALES REPRESENTATIVES; RESIDENCY PROGRAMS; DRUG COMPANIES; PHYSICIANS; FACULTY; BEHAVIOR; POLICIES; GIFTS AB PURPOSE: little is known about the factors that influence housestaff attitudes toward pharmaceutical industry promotions or, how such attitudes correlate with physician behaviors. We studied these attitudes and practices among internal medicine housestaff: SUBJECTS AND METHODS: Confidential surveys about attitudes and behaviors toward industry gifts were distributed to 1st- and 2nd-year residents at a university-based internal medicine residency program. RESULTS: Ninety percent of the residents (105 of 117) completed the survey. A majority of respondents considered seven of nine types of promotions appropriate. Residents judged the appropriateness of promotions on the basis of their cost (median percentage of items considered appropriate 100% for inexpensive items vs. 60% for expensive ones) more than on the basis of their educational value (80% for educational items vs. 75% for noneducational ones; P < .001 for comparison of appropriateness based on cost vs. educational value). Behaviors were often inconsistent with altitudes; every resident who considered conference lunches (n = 13) and pens (n = 18) inappropriate had accepted these gifts. Most respondents (61%) stated that industry promotions and contacts did not influence their own prescribing, but only 16% believed other physicians were similarly unaffected (P < .0001). Nonetheless, more than two thirds of residents agreed that it is appropriate for a medical institution to have rules on industry interactions with residents and faculty. CONCLUSIONS: Residents hold generally positive attitudes toward gifts from industry, believe they are not influenced by them, and report behaviors that are often inconsistent with their attitudes. Thoughtful education and policy programs may help residents learn to critically appraise these gifts. (C) 2001 by Excerpta Medica, Inc. C1 San Francisco Vet Affairs Med Ctr, VA Natl Qual Scholars Program, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, Div Gen Internal Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. RP Steinman, MA (reprint author), San Francisco Vet Affairs Med Ctr, VA Natl Qual Scholars Program, VA Box 111G,Clement St, San Francisco, CA 94121 USA. FU NIA NIH HHS [1 P30 AG15272]; PHS HHS [5 D28 HP 19179-18] NR 23 TC 149 Z9 152 U1 2 U2 7 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 2001 VL 110 IS 7 BP 551 EP 557 DI 10.1016/S0002-9343(01)00660-X PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 430CM UT WOS:000168556000006 PM 11347622 ER PT J AU Romo, LV Curtin, HD AF Romo, LV Curtin, HD TI Anomalous facial nerve canal with cochlear malformations SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID INNER-EAR AB BACKGROUND AND PURPOSE: Anteromedial "migration" of the fil st segment of the facial nerve canal has been previously identified in a patient with a non-Mondini-type cochlear malformation. In this study, several patients with the same facial nerve canal anomaly were reviewed to assess for the association and type of cochlear malformation. METHODS: CT scans of the temporal bone of 15 patients with anteromedial migration of the first segment of the facial nerve canal were collected from routine departmental examinations, In seven patients, the anomalous course was bilateral, for a total of 22 cases. The migration was graded relative to normal as either mild/moderate or pronounced, The cochlea in each of these cases was examined for the presence and size of the basilar, second, and apical turns, The turns were either absent, small, normal, or enlarged, The CT scans of five patients with eight Mondini malformations were examined for comparison. RESULTS: The degree of the facial nerve migration was pronounced in nine cases and mild/ moderate in 13. All 22 of these cases had associated cochlear abnormalities of the non-Mondini variety, These included common cavity anomalies with lack of definition between the cochlea and vestibule (five cases), cochleae with enlarged basilar turns and absent second or third turns (five cases), and cochleae with small or normal basilar turns with small or absent second or third turns (12 cases). None of the patients with Mondini-type cochlear malformations had anteromedial migration of the facial nerve canal. CONCLUSIONS: Anteromedial migration of the facial nerve canal occurs in association with some cochlear malformations, It did not occur in association with the Mondini malformations. A cochlea with a Mondini malformation, being similar in size to a normal cochlea, may physically prohibit such a deviation in course. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Romo, LV (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. NR 20 TC 19 Z9 24 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 MAY PY 2001 VL 22 IS 5 BP 838 EP 844 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 432FM UT WOS:000168681600009 PM 11337325 ER PT J AU Costa, JR Krause, M Freidman, E D'Amico, DJ AF Costa, JR Krause, M Freidman, E D'Amico, DJ TI Central retinal vein occlusion in a patient with thrombotic thrombocytopenic purpura SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To describe the occurrence of central retinal vein occlusion in a patient with thrombotic thrombocytopenic purpura, METHODS: Case report. RESULTS: A 52-year-old woman developed central retinal vein occlusion in the acute phase of thrombotic thrombocytopenic purpura, followed by iris neovascularization only 1 month after the onset of central retinal vein occlusion. Color Doppler imaging of the affected eye showed an increased resistive index of the central retinal artery and reduced blood flow velocity of the central retinal vein compared to the fellow eye. CONCLUSION: We describe a rare association between central retinal vein occlusion and thrombotic thrombocytopenic purpura with rapid evolution of iris neovascularization. Our case demonstrates that close ophthalmologic attention is important in thrombotic thrombocytopenic purpura. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. RP D'Amico, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY PY 2001 VL 131 IS 5 BP 669 EP 671 DI 10.1016/S0002-9394(00)00875-8 PG 3 WC Ophthalmology SC Ophthalmology GA 431AN UT WOS:000168609900025 PM 11336953 ER PT J AU Musi, N Hayashi, T Fujii, N Hirshman, MF Witters, LA Goodyear, LJ AF Musi, N Hayashi, T Fujii, N Hirshman, MF Witters, LA Goodyear, LJ TI AMP-activated protein kinase activity and glucose uptake in rat skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE adenosine 5 '-monophosphate-activated protein kinase; contraction ID ACETYL-COA CARBOXYLASE; TRANSPORTER TRANSLOCATION; GLUT4 TRANSLOCATION; EXERCISE INTENSITY; MALONYL-COA; INSULIN; CONTRACTION; METABOLISM; MECHANISM; ISOFORM AB The AMP-activated protein kinase (AMPK) has been hypothesized to mediate contraction and 5-aminoimidazole-4-carboxamide 1-beta -D-ribonucleoside (AICAR)-induced increases in glucose uptake in skeletal muscle. The purpose of the current study was to determine whether treadmill exercise and isolated muscle contractions in rat skeletal muscle increase the activity of the AMPK alpha1 and AMPK alpha2 catalytic subunits in a dose-dependent manner and to evaluate the effects of the putative AMPK inhibitors adenine 9-beta -D-arabinofuranoside (ara-A), 8-bromo-AMP, and iodotubercidin on AMPK activity and 3-O-methyl-D-glucose (3-MG) uptake. There were dose-dependent increases in AMPK alpha2 activity and 3-MG uptake in rat epitrochlearis muscles with treadmill running exercise but no effect of exercise on AMPK alpha1 activity. Tetanic contractions of isolated epitrochlearis muscles in vitro significantly increased the activity of both AMPK isoforms in a dose-dependent manner and at a similar rate compared with increases in 3-MG uptake. In isolated muscles, the putative AMPK inhibitors ara-A, 8-bromo-AMP, and iodotubercidin fully inhibited AICAR-stimulated AMPK alpha2 activity and 3-MG uptake but had little effect on AMPK alpha1 activity, in contrast, these compounds had absent or minimal effects on contraction-stimulated AMPK alpha1 and -alpha2 activity and 3-MG uptake. Although the AMPK alpha1 and -alpha2 isoforms are activated during tetanic muscle contractions in vitro, in fast-glycolytic fibers, the activation of AMPK alpha2-containing complexes may be more important in regulating exercise-mediated skeletal muscle metabolism in vivo. Development of new compounds will be required to study contraction regulation of AMPK by pharmacological inhibition. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Dartmouth Med Sch, Dept Med & Biochem, Endocrine Metab Div, Hanover, NH USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR-42338, AR-45670]; NIDDK NIH HHS [DK-35712] NR 44 TC 152 Z9 156 U1 0 U2 3 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 MAY PY 2001 VL 280 IS 5 BP E677 EP E684 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 422NU UT WOS:000168125800001 PM 11287349 ER PT J AU Steil, GM Trivedi, N Jonas, JC Hasenkamp, WM Sharma, A Bonner-Weir, S Weir, GC AF Steil, GM Trivedi, N Jonas, JC Hasenkamp, WM Sharma, A Bonner-Weir, S Weir, GC TI Adaptation of beta-cell mass to substrate oversupply: enhanced function with normal gene expression SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE insulin resistance; insulin secretion; beta-cell; mitosis; maturity onset diabetes of the young ID STIMULATED INSULIN-SECRETION; DEPENDENT DIABETES-MELLITUS; INVIVO GLUCOSE INFUSIONS; CIRCULATING FATTY-ACIDS; CHRONIC HYPERGLYCEMIA; IN-VIVO; PANCREAS DEVELOPMENT; NORMAL RATS; TRANSCRIPTION; PATHOGENESIS AB Although type 2 diabetes mellitus is associated with insulin resistance, many individuals compensate by increasing insulin secretion. Putative mechanisms underlying this compensation were assessed in the present study by use of 4-day glucose (GLC; 35% Glc, 2 ml/h) and lipid (LIH; 10% Intralipid + 20 U/ml heparin; 2 ml/h) infusions to rats. Within 2 days of beginning the infusion of either lipid or glucose, plasma glucose profiles were normalized (relative to saline-infused control rats; SAL; 0.45% 2 ml/h). During glucose infusion, plasma glucose was maintained in the normal range by an approximately twofold increase in plasma insulin and an similar to 80% increase in beta -cell mass. During LIH infusion, glucose profiles were also maintained in the normal range. Plasma insulin responses during feeding were doubled, and beta -cell mass increased 54%. For both groups, the increase in beta -cell mass was associated with increased beta -cell proliferation (98% increase during GLC and 125% increase during LIH). At the end of the 4-day infusions, no significant changes were observed in islet-specific gene transcription (i.e., the expression of islet hormone genes, glucose metabolism genes, and insulin transcription factors were unaffected). Two days after termination of the infusions, the glucose-stimulated plasma insulin response was increased similar to 67% in glucose-infused animals. No sustained effect on insulin secretory capacity was observed in the LIH animals. The increase in plasma insulin response after glucose infusion was achieved in the absence of any change in insulin clearance. We conclude that, in rats, an increase in insulin demand after an increase in glucose appearance or free fatty acid leads to an increase in beta -cell mass, mediated in part by an increase in beta -cell proliferation, and that these compensatory changes lead to increased insulin secretion, normal plasma glucose levels, and the maintenance of normal islet gene expression. C1 Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Steil, GM (reprint author), MiniMed Inc, 18000 Devonshire St, Northridge, CA 91325 USA. RI Jonas, Jean-Christophe/C-6766-2011 OI Jonas, Jean-Christophe/0000-0001-9882-5438 FU NIDDK NIH HHS [DK-35449, DK-36836, DK-44523] NR 50 TC 102 Z9 104 U1 0 U2 7 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 MAY PY 2001 VL 280 IS 5 BP E788 EP E796 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 422NU UT WOS:000168125800014 PM 11287362 ER PT J AU Miampamba, M Yang, H Sharkey, KA Tache, Y AF Miampamba, M Yang, H Sharkey, KA Tache, Y TI Intracisternal TRH analog induces Fos expression in gastric myenteric neurons and glia in conscious rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE RX-77368; immediate-early gene; atropine; hexamethonium; vesicular acetylcholine transporter; enteric nervous system ID THYROTROPIN-RELEASING-HORMONE; ENTERIC NERVOUS-SYSTEM; VESICULAR ACETYLCHOLINE TRANSPORTER; DORSAL MOTOR NUCLEUS; PIG SMALL-INTESTINE; GUINEA-PIG; C-FOS; GENE-EXPRESSION; IMMUNOHISTOCHEMICAL LOCALIZATION; CHOLINE-ACETYLTRANSFERASE AB Activation of gastric myenteric cells by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368, at a dose inducing near maximal vagal cholinergic stimulation of gastric functions, was investigated in conscious rats. Fos immunoreactivity was assessed in gastric longitudinal muscle-myenteric plexus whole mount preparations 90 min after intracisternal injection. Fos-immunoreactive cells were rare in controls (similar to1 cell/ganglion), whereas intracisternal RX-77368 (50 ng) increased the number to 24.8 +/- 1.8 and 26.8 +/- 2.2 cells/ganglion in the corpus and antrum, respectively. Hexamethonium (20 mg/kg sc) prevented Fos expression by 90%, whereas atropine (2 mg/kg sc) had no effect. The neuronal marker protein gene product 9.5 and the glial markers S-100 and glial fibrillary acidic proteins showed that RX-77368 induced Fos in both myenteric neurons and glia. Vesicular ACh transporter and calretinin were detected around the activated myenteric neurons. These results indicated that central vagal efferent stimulation by intracisternal RX-77368 activates gastric myenteric neurons as well as glial cells mainly through nicotinic ACh receptors in conscious rats. C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Univ Calgary, Dept Physiol & Biophys, Neurosci Res Grp, Calgary, AB T2N 4N1, Canada. RP Miampamba, M (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-33061] NR 53 TC 33 Z9 33 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 MAY PY 2001 VL 280 IS 5 BP G979 EP G991 PG 13 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 424CK UT WOS:000168214400025 PM 11292608 ER PT J AU Chandrasekar, B Nelson, JF Colston, JT Freeman, GL AF Chandrasekar, B Nelson, JF Colston, JT Freeman, GL TI Calorie restriction attenuates inflammatory responses to myocardial ischemia-reperfusion injury SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cytokines; free radicals; glutathione; energy intake ID FACTOR-KAPPA-B; TUMOR-NECROSIS-FACTOR; OXIDATIVE STRESS; FOOD RESTRICTION; ANTIOXIDANT DEFENSES; ADRENOCORTICOTROPIC HORMONE; PROINFLAMMATORY CYTOKINE; POSTISCHEMIC MYOCARDIUM; SUPEROXIDE-DISMUTASE; DIETARY RESTRICTION AB The life-prolonging effects of calorie restriction (CR) may be due to reduced damage from cumulative oxidative stress. Our goal was to determine the long-term effects of moderate dietary CR on the myocardial response to reperfusion after a single episode of sublethal ischemia. Male Fisher 344 rats were fed either an ad libitum (AL) or CR (40% less calories) diet. At age 12 mo the animals were anaesthetized and subjected to thoracotomy and a 15-min left-anterior descending coronary artery occlusion. The hearts were reperfused for various periods. GSH and GSSG levels, nuclear factor-kappaB (NF-kappaB) DNA binding activity, cytokine, and antioxidant enzyme expression were assessed in the ischemic zones. Sham-operated animals served as controls. Compared with the AL diet, chronic CR limited oxidative stress as seen by rapid recovery in GSH levels in previously ischemic myocardium. CR reduced DNA binding activity of NF-kappaB. The kappaB-responsive cytokines interleukin-1 beta and tumor necrosis factor-alpha were transiently expressed in the CR group but persisted longer in the AL group. Furthermore, expression of manganese superoxide dismutase, a key antioxidant enzyme, was significantly delayed in the AL group. Collectively these data indicate that CR significantly attenuates myocardial oxidative stress and the postischemic inflammatory response. C1 Univ Texas, Hlth Sci Ctr, Div Cardiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Div Physiol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Nelson, JF (reprint author), Univ Texas, Hlth Sci Ctr, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [AG-01188-18] NR 43 TC 56 Z9 58 U1 0 U2 1 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 MAY PY 2001 VL 280 IS 5 BP H2094 EP H2102 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 420WE UT WOS:000168027600021 PM 11299211 ER PT J AU Huang, Y Tracy, R Walsberg, GE Makkinje, A Fang, P Brown, D Van Hoek, AN AF Huang, Y Tracy, R Walsberg, GE Makkinje, A Fang, P Brown, D Van Hoek, AN TI Absence of aquaporin-4 water channels from kidneys of the desert rodent Dipodomys merriami merriami SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE freeze fracture electron microscopy; immunocytochemistry; Merriam's kangaroo rat; in situ hybridization ID MICE; GLYCEROL; PERMEABILITY; EXPRESSION; PHYSIOLOGY; MEMBRANES; PROTEINS; FAMILY; MUSCLE; BRAIN AB Recently, we found that aquaporin-4 (AQP4) is expressed in the S3 segment of renal proximal tubules of mice but not in rat proximal tubules. Because mice have relatively larger papillae than rats, it was proposed that the renal distribution of AQP4 in various species could be related to their maximum urinary concentrating ability. Therefore, kidneys and other tissues of Merriam's desert kangaroo rat, Dipodomys merriami merriami, which produce extremely concentrated urine (up to 5,000 mosmol/kgH(2)O), were examined for AQP4 expression and localization. Contrary to our expectation, AQP4 immunostaining was undetectable in any region of the kidney, and the absence of AQP4 protein was confirmed by Western blotting. By freeze fracture electron microscopy, orthogonal arrays of intramembraneous particles (OAPs) were not detectable in plasma membranes of principal cells and proximal tubules. However, AQP4 protein was readily detectable in gastric parietal and brain astroglial cells. Northern blotting failed to detect AQP4 mRNA in kangaroo rat kidneys, whereas both in situ hybridization and RT-PCR experiments did reveal AQP4 mRNA in collecting ducts and proximal tubules of the S3 segment. These results suggest that renal expression of AQP4 in the kangaroo rat kidney is regulated at the transcriptional or translational level, and the absence of AQP4 may be critical for the extreme urinary concentration that occurs in this species. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Arizona State Univ, Dept Biol, Tempe, AZ 85287 USA. Massachusetts Gen Hosp, Diabet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Van Hoek, AN (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM vanhoek@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK-38452, KO1 DK-02655, R01-DK-55864] NR 32 TC 22 Z9 23 U1 1 U2 18 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 MAY PY 2001 VL 280 IS 5 BP F794 EP F802 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 418VJ UT WOS:000167914600007 PM 11292621 ER PT J AU Rifas-Shiman, SL Gillman, MW Field, AE Frazier, AL Berkey, CS Tomeo, CA Colditz, GA AF Rifas-Shiman, SL Gillman, MW Field, AE Frazier, AL Berkey, CS Tomeo, CA Colditz, GA TI Comparing physical activity questionnaires for youth - Seasonal vs annual format SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE adolescence; exercise; questionnaires; seasons ID REDUCED RISK; REPRODUCIBILITY; VALIDITY; CANCER; ADOLESCENTS; POPULATION; CHILDREN AB Background: In large cohort studies of older children, self-report is the only practical way to assess physical activity. Assessing usual activity over the entire year is desirable, but children and adolescents may overestimate activities with high seasonal variability. Use of questionnaires in which individuals report each activity by season may improve accuracy. Methods: A total of 6782 girls and 5110 boys, aged 9-14 years in 1996, completed self-administered activity questionnaires in 1996 and in 1997. In 1996, participants reported the average time spent in each of 17 activities during the previous 12 months; in 1997, we also asked for the average time spent in the previous year, but within each of the four seasons. Results: Girls reported a median of 12.8 hours/week total activity in 1996 and 10.4 hours/week in 1997. For boys, the estimates were 15.5 hours/week and 13.4 hours/week, respectively. Girls and boys within 1-year age strata (e.g., comparison of 10-year olds in 1996 with 10-year olds in 1997) reported an average of 3.7 and 3.1 fewer hours per week, respectively, on the 1997 seasonal format versus the 1996 annual format questionnaire. In longitudinal analyses, the difference between the annual and the seasonal estimates was greater if participants did the activity in fewer seasons in 1997. Conclusions: In comparison to an annual format questionnaire, a seasonal format questionnaire may improve accuracy of self-report of physical activity by reducing over-reporting of activities in which pre-adolescents and adolescents engage in fewer seasons. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Gillman, MW (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 126 Brookline Ave,Suite 200, Boston, MA 02215 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NHLBI NIH HHS [HL 03533]; NIDDK NIH HHS [DK 46834] NR 16 TC 43 Z9 43 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY PY 2001 VL 20 IS 4 BP 282 EP 285 DI 10.1016/S0749-3797(01)00296-3 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 426LV UT WOS:000168351400007 PM 11331117 ER PT J AU Barsky, AJ Ahern, DK Bailey, ED Saintfort, R Liu, EB Peekna, HM AF Barsky, AJ Ahern, DK Bailey, ED Saintfort, R Liu, EB Peekna, HM TI Hypochondriacal patients' appraisal of health and physical risks SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID III-R HYPOCHONDRIASIS; UNREALISTIC OPTIMISM; SOMATOSENSORY AMPLIFICATION; PERCEPTIONS; SUSCEPTIBILITY; ILLNESS; DISEASE AB Objective: The authors' goal was to assess the degree to which hypochondriasis is accompanied by a heightened sense of risk of disease and other physical hazards. Method: Fifty-six patients meeting DSM-III-R criteria for hypochondriasis were compared with 127 nonhypochondriacal patients from the same primary care setting. Both groups completed a self-report questionnaire assessing the degree to which they felt at risk of developing various medical diseases or being subject to injury from accidents or criminal assault. Results: Both groups of patients exhibited an optimistic bias in that they considered themselves to be less at risk than others of their age and sex. However, the hypochondriacal group had a significantly higher total risk score than did the nonhypochondriacal group. In large part, this intergroup difference was the result of the hypochondriacal patients' perception that they were likely to develop various diseases. The hypochondriacal group did not score significantly higher than the comparison group in estimating their risk of succumbing to accidents and criminal victimization. Perceived risk was significantly associated with the self-reported tendency to amplify benign bodily sensa ions. Conclusions: An exaggerated appraisal of risk, jeopardy, and vulnerability to disease may be part of the cognitive distortion seen in hypochondriasis. If this is confirmed, cognitive and behavioral therapies for hypochondriasis may need to include a focus on these patients' understanding and appraisal of risk. C1 Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. RP Barsky, AJ (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. FU NIMH NIH HHS [MH-40487] NR 24 TC 36 Z9 38 U1 2 U2 9 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 2001 VL 158 IS 5 BP 783 EP 787 DI 10.1176/appi.ajp.158.5.783 PG 5 WC Psychiatry SC Psychiatry GA 428UD UT WOS:000168479000020 PM 11329402 ER PT J AU Ard, CF Natowicz, MR AF Ard, CF Natowicz, MR TI A seat at the table: Membership in federal advisory committees evaluating public policy in genetics SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HUMAN-GENOME-PROJECT; ACCOUNTABILITY AB Objectives. This study examined who participates in federal government advisory committees regarding public policy in human and medical genetics, what parties they represent, and to what extent the general public is meaningfully represented. Methods. Analysis focused on 7 federal government documents published from January 1990 to February 1995. Advisors were categorized into 4 groups based on the professional affiliations that were listed in the publications. After a search of several references and databases, the study examined whether these individuals also had other affiliations not listed in the government publications, Results. Individuals whose principal affiliations were with academia (n= 32, 44%) or industry (n= 19; 26%) represented nearly three fourths of the sample, followed by government employees (n= 13; 18%) and consumer advocates (n = 8; 11 %). At least 16% of the advisors serving the federal committees, mostly members of academia, had a dual affiliation. Conclusions. These data indicate that the public has modest representation on key federal advisory committees making policy recommendations regarding human genetics technology and clinical practice and that there is ample room for additional public participation. C1 Eunice Kennedy Shriver Ctr Mental Retardat Inc, Div Med Genet, Waltham, MA 02452 USA. Brandeis Univ, Florence Heller Grad Sch Adv Studies Social Welf, Waltham, MA 02254 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Natowicz, MR (reprint author), Eunice Kennedy Shriver Ctr Mental Retardat Inc, Div Med Genet, 200 Trapelo Rd, Waltham, MA 02452 USA. FU PHS HHS [MCJ-251003-09-00] NR 43 TC 9 Z9 9 U1 2 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 2001 VL 91 IS 5 BP 787 EP 790 DI 10.2105/AJPH.91.5.787 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BP UT WOS:000170345300021 PM 11344888 ER PT J AU Chao, S Mullins, ME Gallagher, L Slanetz, PJ AF Chao, S Mullins, ME Gallagher, L Slanetz, PJ TI Primary non-Hodgkin's lymphoma of the femur SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID BONE C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Mullins, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders House, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 2001 VL 176 IS 5 BP 1160 EP 1160 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 424AA UT WOS:000168208900012 PM 11312172 ER PT J AU Werner, SL Gill, TJ Murray, TA Cook, TD Hawkins, RJ AF Werner, SL Gill, TJ Murray, TA Cook, TD Hawkins, RJ TI Relationships between throwing mechanics and shoulder distraction in professional baseball pitchers SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article ID BIOMECHANICS; ELBOW AB The extreme forces and torques and the high speeds and excessive ranges of motion of baseball pitching place tremendous stress on the soft tissues of the throwing shoulder. Little is known about the relationship between pitching mechanics and shoulder joint stress, especially in professional athletes. The purpose of this study was to quantify joint loads and kinematic parameters of pitching mechanics at the major league level and to study their relationships. Three-dimensional, high-speed video data were collected on 40 professional pitchers during the 1998 Cactus League spring training. A clinically significant distraction force was calculated at the shoulder joint, which reached an average peak value of 947 +/- 162 N (108% +/- 16% body weight). Descriptive statistics and a multiple linear regression analysis were used to relate shoulder distraction to kinematic and kinetic parameters of pitching mechanics. This study was undertaken not only to investigate the peak forces and torques on the shoulder, but also to identify potential areas of intervention that might prevent throwing injuries. Knowledge of joint ranges of motion, angular velocities, and joint-reaction forces can provide a scientific basis for improved preventive and rehabilitative protocols for baseball pitchers. C1 Steadman Hawkins Sports Med Fdn, Steadman Hawkins Clin, Vail, CO 81657 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Hawkins, RJ (reprint author), Steadman Hawkins Sports Med Fdn, Steadman Hawkins Clin, 181 W Meadow Dr,Suite 400, Vail, CO 81657 USA. NR 13 TC 84 Z9 84 U1 6 U2 15 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD MAY-JUN PY 2001 VL 29 IS 3 BP 354 EP 358 PG 5 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 435JQ UT WOS:000168878700017 PM 11394608 ER PT J AU Slater, MS Holland, J Faigel, DO Sheppard, BC Deveney, CW AF Slater, MS Holland, J Faigel, DO Sheppard, BC Deveney, CW TI Does neoadjuvant chemoradiation downstage esophageal carcinoma? SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 10-11, 2000 CL COEURD ALENE, IDAHO SP N Pacific Surg Assoc DE esophageal carcinoma; chemoradiotherapy ID SQUAMOUS-CELL CARCINOMA; COMBINED-MODALITY THERAPY; RADIATION-THERAPY; ENDOSCOPIC ULTRASONOGRAPHY; TRANSHIATAL ESOPHAGECTOMY; CANCER; CHEMOTHERAPY; ADENOCARCINOMA; RESECTION; SURGERY AB Background: Neoadjuvant chemoradiotherapy is administered to patients with esophageal carcinoma with the belief that this will both downstage the tumor and improve survival. Endoscopic ultrasound (EUS) is currently the most accurate method of staging esophageal cancer for tumor (T) and lymph node (N) status. Because both EUS and neoadjuvant therapy for esophageal carcinoma are relatively new, there are few data examining the relationship between EUS stage and histological stage (the stage after resection) in patients receiving neoadjuvant therapy. Methods: To determine the effect of neoadjuvant chemoradiotherapy on T and N stage as determined by EUS,we retrospectively compared two groups of patients with esophageal cancer staged by EUS. One group (33 patients) underwent neoadjuvant therapy (Walsh protocol: 5-fluorouracil, cisplatin, and 4000 mds of external beam radiation) followed by resection. The second group (22 patients), a control group, underwent resection without neoadjuvant therapy. We then compared histological stage to determine if there was a downstaging in the patients receiving neoadjuvant therapy. Survival was evaluated as well. Results: EUS accurately predicted histologic stage. In the control group EUS overestimated T stage in 3 of 22 (13%), underestimated N stage in 2 of 22 (9%), and overestimated N stage in 2 of 22 (9%) of patients. Preoperative radiochemotherapy downstaged (preoperative EUS stage versus pathologic specimen) 12 of 33 (36%) Of patients whereas only 1 of 22 (5%) of patients in the control group was downstaged. Complete response (no tumor found in the surgical specimen) was observed in 5 of 33 (15%) of patients receiving radiochemotherapy. Survival was prolonged significantly in patients receiving radiochemotherapy: 20.6 months versus 9.6 months for those (stage II or III) patients not receiving radiochemotherapy (P < 0.01). Operative time, operative blood loss, and length of stay were not significantly different between groups. Perioperative mortality was higher in the radiochemotherapy group (13%) compared with the no radiochemotherapy group (5%) but did not achieve statistical significance. Conclusions: EUS accurately stages esophageal carcinoma. Neoadjuvant radiochemotherapy downstages esophageal carcinoma for T and N status. In our nonrandomized study, neoadjuvant therapy conferred a significant survival advantage. Operative risk appears to be increased in patients receiving neoadjuvant radiochemotherapy prior to esophagectomy. (C) 2001 Excerpta Medica, Inc. All rights reserved. C1 Portland VA Med Ctr, Vet Adm Hosp, Surg Serv, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Surg Serv, Portland, OR 97207 USA. RP Deveney, CW (reprint author), Portland VA Med Ctr, Vet Adm Hosp, Surg Serv, P3SURG,POB 1034, Portland, OR 97207 USA. NR 26 TC 35 Z9 38 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 2001 VL 181 IS 5 BP 440 EP 444 DI 10.1016/S0002-9610(01)00601-8 PG 5 WC Surgery SC Surgery GA 451WQ UT WOS:000169825800012 PM 11448438 ER PT J AU Luna, G Adye, B Haun-Hood, M Berry, M Taylor, L Thorn, R AF Luna, G Adye, B Haun-Hood, M Berry, M Taylor, L Thorn, R TI Intentional injury treated in community hospitals SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 10-11, 2000 CL COEURD ALENE, IDAHO SP N Pacific Surg Assoc DE injury; trauma; intentional; violent; community; cost ID FIREARMS; COSTS AB Background: The impact of intentional injury in major metropolitan trauma centers has been established. Nonaccidental injury has become an increasingly important component of trauma care in mid-sized urban areas. To determine the medical and economic impact of personal violence in the Spokane, Washington, community we undertook a 5-year retrospective review. Patients and methods: Trauma registries were used to identify all victims of intentional injury admitted between May 1, 1994, and April 31, 1999. Demographic data, blood alcohol, mechanism, injury severity, hospital course, and outcome were abstracted from the registries. Financial data were obtained from hospital financial offices. Setting: Spokane, Washington, has a population of 200,000 with 400,000 in the metropolitan area. Trauma patients are triaged to hospitals according to Washington Administrative Code guidelines, supervised by central medical control. The two level ii and two level m facilities are staffed by private practice surgeons and serve a referral area of 650,000. Results: Five hundred eighty-one intentional injury patients were admitted. This represented 15% of all significant injuries. Males accounted for 80% of the patients and 84% were Caucasian. The mean patient age was 30 years, only one quarter were listed as employed. Sixteen percent of the injuries were self-inflicted, gunshot was the most common mechanism (39%). Alcohol was involved in one half of the injuries. Sixty-three patients died, 39 died prior to intensive care unit admission. Hospital stay averaged 6.4 days, with a mean hospital charge of $18,000. Hospitals were reimbursed at 67%. Surgeons collected 31% of billed fees. Fewer than one third of patients had any form of private insurance. Conclusions: Intentional injury is a significant component of trauma care in our community. Patients are seriously injured and the fatality rate is high. Care is expensive and poorly funded. (C) 2001 Excerpta Medica, Inc. All rights reserved. C1 Holy Family Hosp, Sacred Heart Med Ctr, Deaconess Med Ctr, Spokane, WA 99204 USA. RP Luna, G (reprint author), Holy Family Hosp, Sacred Heart Med Ctr, Deaconess Med Ctr, 104 West Fifth,Suite 350 East, Spokane, WA 99204 USA. NR 13 TC 9 Z9 9 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 2001 VL 181 IS 5 BP 463 EP 465 DI 10.1016/S0002-9610(01)00598-0 PG 3 WC Surgery SC Surgery GA 451WQ UT WOS:000169825800018 PM 11448444 ER PT J AU Rabkin, JM de la Melena, V Orloff, SL Corless, CL Rosen, HR Olyaei, AJ AF Rabkin, JM de la Melena, V Orloff, SL Corless, CL Rosen, HR Olyaei, AJ TI Late mortality after orthotopic liver transplantation SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the North-Pacific-Surgical-Association CY NOV 10-11, 2000 CL COEURD ALENE, IDAHO SP N Pacific Surg Assoc DE liver transplantation; survival; late mortality; allograft failure ID RENAL-FAILURE; RISK-FACTORS; RETRANSPLANTATION; CYCLOSPORINE; INFECTIONS; RECIPIENTS; REJECTION; HEPATITIS AB Background: Mortality within the first year after orthotopic liver transplantation (OLTx) is usually due to infection or allograft failure. Late complications leading to death after OLTx have not been extensively evaluated. The aim of this study was to determine the incidence of late mortality and to identify the most common causes and risk factors associated with late mortality after OLTx. Methods: A total of 479 OLTx were performed in 459 patients (320 males, 139 females; mean age 47 years, range 13 to 69) between September 1991 and April 2000. All patient deaths among liver transplant recipients who survived more than 1 year after transplantation (follow-up mean 3.4 years, median 3, range 1 to 8.6) were reviewed. Results: In all, 122 allografts (24%) were lost in 109 patients during the study period (24%). Seventy-five allografts were lost in 69 patients by 1 year (15%), Forty-seven allografts were lost in 40 patients who survived at least 1 year (9.6%). Actuarial survivals at 2 years, 5 years, and 9 years were 95%, 85%, and 80%, respectively (based on 100% survival at 1 year). The causes of the late mortality were malignancy (9 patients), disease recurrence (8), late infection (6), renal failure complications (5), cardiovascular complications (4), chronic rejection (3), gastrointestinal hemorrhage (2), medication noncompliance (1), and unknown (2). Conclusions: Malignancy and disease recurrence are the major causes of late mortality among adult OLTx recipients. Pharmacologic immunosuppression is associated with many of the causes of late mortality. Advances in immunosuppression with less toxicity may improve long-term survival after OLTx. (C) 2001 Excerpta Medica, Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Surg, Div Abdominal Organ Transplantat, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. RP Rabkin, JM (reprint author), Oregon Hlth Sci Univ, Dept Surg, Div Abdominal Organ Transplantat, 3181 SW Sam Jackson Pk Road,L590, Portland, OR 97201 USA. NR 25 TC 75 Z9 81 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 2001 VL 181 IS 5 BP 475 EP 479 DI 10.1016/S0002-9610(01)00595-5 PG 5 WC Surgery SC Surgery GA 451WQ UT WOS:000169825800021 PM 11448447 ER PT J AU Baker, PM Oliva, E Young, RH Talerman, A Scully, RE AF Baker, PM Oliva, E Young, RH Talerman, A Scully, RE TI Ovarian mucinous carcinoids including some with a carcinomatous component - A report of 17 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE mucinous carcinoid; goblet cell carcinoid; ovarian neoplasm; mucinous carcinoid with carcinoma; prognostic factors ID BILATERAL KRUKENBERG TUMORS; CLINICOPATHOLOGIC ANALYSIS; NEUROENDOCRINE CARCINOMA; ADENOCARCINOID TUMOR; VERMIFORM APPENDIX; CELL-CARCINOMA; METASTASIS; TISSUE AB Only rare primary mucinous (goblet cell) carcinoids of the ovary have been reported, and their clinicopathologic features have not been well delineated. The authors studied 17 tramples From patients 14 to 74 years of age. The clinical presentations were similar to those of ovarian neoplasms in general. The tumors ranged from 0.8 to 30 cm in diameter. In six cases the tumor was in the wall of a mature cystic tetatoma, appearing grossly as solid nodules or areas of thickening in four of them, six tumors were entirely solid, and five were solid associated with other types of cystic tumor. The tumors were divided into three groups on the basis of their microscopic features. Six neoplasms, designated "well differentiated," were composed of small glands, many of which floated in pools of mucin. The glands were lined by goblet cells and columnar cells, some of which were of neuroendocrine type. Three turners, designated "atypical," were characterized by crowded glands, some of which were confluent, small islands with a cribriform pattern. and scattered microcystic glands. The glands were lined by cuboidal to columnar cells, some of them neuroendocrine. admixed with goblet cells. Eight tumors, designated "carcinoma arising in mucinous carcinoid," contained islands and larger nodules of tumor cells, or closely packed glands, as well as single cells, mainly of the signet ring cell type. Most of the calls were devoid of mucin and were severely atypical with marked mitotic activity. Necrosis was present in all eight rumors. Seven of the right tumors with a carcinomatous component contained at least minor foci of well-differentiated mucinous carcinoid, the eighth contained only foci of atypical mucinous carcinoid. The neuroendocrine nature of a variable proportion of the cells in all three groups was demonstrated by staining for neuroendocrine markers. The mucinous nature of other cells was confirmed by mucicarmine or Alcian blue stains. The ovary contained an intrinsic component of trabecular and insular carcinoid. and of strumal carcinoid in one case each, an adjacent mature cystic teratoma in six cases, mucinous cystadenocarcinoma in three cases, and borderline mucinous cystic tumor, borderline Brenner tumor, and epidermoid cyst in one case each. Fifteen tumors were stage I, one was stage II, and one was stage III. The last two tumors had a carcinomatous component. Follow-up data were available for 15 patients, 12 were alive and free of tumor 2.3 to 14 years (average, 4.7 years) after the ovarian tumor was excised. One patient. whose rumor had a carcinomatous component, died 3 years postoperatively of unrelated causes. Two patients, both of whom had a carcinomatous component in their tumor, died 9 and 12 months postoperatively. Primary mucinous carcinoids must be distinguished from metastatic mucinous carcinoid tumors from the appendix or elsewhere. Features supporting an ovarian origin are the additional presence in the specimen of teratoma or an ovarian surface epithelial tumor, an absence of blood vessel or lymphatic space invasion, and confinement to a single ovary. Similar features help to distinguish mucinous carcinoids from Krukenberg rumors. Mucinous carcinoids should also he distinguished from strumal carcinoids, which can contain mucinous glands, and insular carcinoid tumors that arise rarely in the wall of a mucinous cystic neoplasm. Although the number of cases in this series is small, the follow-up data suggest that the degree of differentiation, particularly the presence of frank carcinoma, is an important prognostic factor. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Thomas Jefferson Univ Hosp, Dept Pathol, Philadelphia, PA 19107 USA. RP Oliva, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. NR 46 TC 57 Z9 65 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 MAY PY 2001 VL 25 IS 5 BP 557 EP 568 DI 10.1097/00000478-200105000-00001 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 427RD UT WOS:000168418500001 PM 11342766 ER PT J AU Cates, JM Rosenberg, AE O'Connell, JX Nielsen, GP AF Cates, JM Rosenberg, AE O'Connell, JX Nielsen, GP TI Chondroblastoma-like chondroma of soft tissue - An underrecognized variant and its differential diagnosis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE soft-tissue chondroma; chondroblastoma; chondroblastoma-like chondroma ID EXTRASKELETAL MYXOID CHONDROSARCOMA; GIANT-CELL TUMOR; TENDON SHEATH; METASTATIC CHONDROBLASTOMA; BENIGN; BONE; REARRANGEMENTS; ABNORMALITIES; DEPOSITION; LESIONS AB Soft-tissue chondromas are usually composed entirely of mature hyaline cartilage. Infrequently, however. they may exhibit morphologic features that result in diagnostic difficulty. The authors report a series of eight hypercellular soft-tissue chondromas composed of enlarged chondrocytes within a variable amount of chondroid matrix that often demonstrated delicate calcifications and contained numerous osteoclast-like multinucleated giant cells. This histologic appearance closely resembles that of chondroblastoma of bone. However, its extraosseous location, dense cellularity, and poorly formed cartilage can cause confusion with more aggressive chondroid neoplasms of soft tissue. The clinicopathologic features of these chondroblastoma-like chondromas are discussed, emphasizing the characteristics that facilitate their accurate identification. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Lab, Boston, MA 02114 USA. Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RI Cates, Justin/D-5927-2014 OI Cates, Justin/0000-0002-7336-5196 NR 58 TC 9 Z9 9 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 MAY PY 2001 VL 25 IS 5 BP 661 EP 666 DI 10.1097/00000478-200105000-00015 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 427RD UT WOS:000168418500015 PM 11342780 ER PT J AU Auchincloss, H AF Auchincloss, H TI In search of the elusive holy grail: The mechanisms and prospects for achieving clinical transplantation tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Review DE deletional; macrochimerism; mechanisms; nondeletional; thymus; tolerance ID BONE-MARROW TRANSPLANTATION; ALLOGRAFT TOLERANCE; CLONAL DELETION; DENDRITIC CELLS; CD95 LIGAND; CHIMERISM; INDUCTION; SURVIVAL; BLOCKING; PATHWAYS C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Transplantat Unit, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Transplantat Unit, Boston, MA 02114 USA. NR 38 TC 48 Z9 48 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 MAY PY 2001 VL 1 IS 1 BP 6 EP 12 DI 10.1034/j.1600-6143.2001.010103.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 512PM UT WOS:000173332800003 PM 12095040 ER PT J AU Holzman, RS Riley, LE Aron, E Fetherston, J AF Holzman, RS Riley, LE Aron, E Fetherston, J TI Perioperative care of a patient with acute fatty liver of pregnancy SO ANESTHESIA AND ANALGESIA LA English DT Article ID PREECLAMPSIA; MANAGEMENT; RECURRENCE; DISEASE C1 Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Newton Wellesley Hosp, Dept Anesthesia, Newton, MA USA. Massachusetts Gen Hosp, Maternal Fetal Med Serv, Boston, MA 02114 USA. Newton Wellesley Hosp, Dept Obstet & Gynecol, Boston, MA USA. RP Holzman, RS (reprint author), Childrens Hosp, Dept Anesthesia, 300 Longwood Ave, Boston, MA 02115 USA. NR 15 TC 7 Z9 8 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 MAY PY 2001 VL 92 IS 5 BP 1268 EP 1270 PG 3 WC Anesthesiology SC Anesthesiology GA 426EB UT WOS:000168335900035 PM 11323360 ER PT J AU Goudsouzian, NG AF Goudsouzian, NG TI Rapacuronium and bronchospasm SO ANESTHESIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goudsouzian, NG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 6 TC 29 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2001 VL 94 IS 5 BP 727 EP 728 DI 10.1097/00000542-200105000-00006 PG 2 WC Anesthesiology SC Anesthesiology GA 428YA UT WOS:000168488200002 PM 11388519 ER PT J AU Goddon, S Fujino, Y Hromi, JM Kacmarek, RM AF Goddon, S Fujino, Y Hromi, JM Kacmarek, RM TI Optimal mean airway pressure during high-frequency oscillation - Predicted by the pressure-volume curve SO ANESTHESIOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; CONVENTIONAL MECHANICAL VENTILATION; LUNG INJURY; FAILURE; RECRUITMENT; SURFACTANT; TRIAL; ATELECTASIS; RABBIT AB Background: A number of groups have recommended setting positive end-expiratory pressure during conventional mechanical ventilation in adults at 2 cm H2O above the lower corner pressure (P-CL) of the inspiratory pressure-volume (P-V) curve of the respiratory system. No equivalent recommendations for the setting of the mean airway pressure (P-aw) during high-frequency oscillation (HFO) exist. The authors questioned if the P-aw resulting in the best oxygenation without hemodynamic compromise during HFO is related to the static P-V curve in a large animal model of acute respiratory distress syndrome. Methods: Saline lung lavage was performed in seven sheep (28 +/- 5 kg, mean +/- SD) until the arterial oxygen partial pressure/fraction of inspired oxygen ratio decreased to 85 +/- 27 mmHg at a positive end-expiratory pressure of 5 cm H2O (initial injury). The P-CL (20 +/- 1 cm H2O) on the inflation Limb and the point of maximum curvature change (PMC; 26 +/- 1 cm H2O) on the deflation limb of the static P-V curve were determined. The sheep were subjected to four 1-h cycles of HFO at different levels of P-aw (P-CL + 2, + 6, + 10, + 14 cm H2O), applied in random order. Each cycle was preceded by a recruitment maneuver at a sustained P-aw of 50 cm H2O for 60 s. Results: High-frequency oscillation with a P-aw of 6 cm H2O above P-CL (P-CL + 6) resulted in a significant improvement in oxygenation (P < 0.01 vs. initial injury). No further improvement in oxygenation was observed with higher P-aw, but cardiac output decreased, pulmonary vascular resistance increased, and oxygen delivery decreased at P-aw greater than P-CL + 6. The PMC on the deflation limb of the P-V curve was equal to the P-CL + 6 (r = 0.77, P < 0.05). Conclusion: In this model of acute respiratory distress syndrome, optimal P-aw during HFO is equal to P-CL + 6, which correlates with the PMC. C1 Massachusetts Gen Hosp, Resp Care Dept Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Dept Lab, Ellison 401, Boston, MA 02114 USA. NR 25 TC 38 Z9 40 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAY PY 2001 VL 94 IS 5 BP 862 EP 869 DI 10.1097/00000542-200105000-00026 PG 8 WC Anesthesiology SC Anesthesiology GA 428YA UT WOS:000168488200022 PM 11388539 ER PT J AU Shank, ES Muth, CM AF Shank, ES Muth, CM TI Diver with decompression injury elevation of serum transaminase levels, and rhabdomyolysis SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID EMBOLISM AB A 43-year-old female recreational scuba diver presented to the emergency department 1 hour after a rapid, uncontrolled ascent. Her presentation included progressing confusion, slow and slurred speech, and complaints of headache and hypesthesia over her forearms and anterior thighs bilaterally. Differential diagnosis included arterial gas embolism and decompression sickness. She underwent recompression therapy with US Navy Table 6 within 120 minutes of her ascent. After recompression therapy, the patient had signs and symptoms consistent with severe rhabdomyolysis, including creatine kinase levels of 36,000 U/L and myoglobinuria. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Hyperbar Med, Boston, MA 02114 USA. Univ Hosp Ulm, Dept Anesthesiol & Intens Care Med, Ulm, Germany. RP Shank, ES (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 3,32 Fruit St, Boston, MA 02114 USA. NR 14 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAY PY 2001 VL 37 IS 5 BP 533 EP 536 DI 10.1067/mem.2001.114320 PG 4 WC Emergency Medicine SC Emergency Medicine GA 429BC UT WOS:000168495300013 PM 11326189 ER PT J AU Lorenz, KA Shapiro, MF Asch, SM Bozzette, SA Hays, RD AF Lorenz, KA Shapiro, MF Asch, SM Bozzette, SA Hays, RD TI Associations of symptoms and health-related quality of life: Findings from a national study of persons with HIV infection SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; OF-LIFE; SERVICES UTILIZATION; PALLIATIVE CARE; UNITED-STATES; COST; AIDS AB Background: Health-related quality of life refers to how well people are able to perform daily activities (functioning) and how they feel about their lives (well-being). The relationship between symptoms and health-related quality of life has not been fully explored, Objective: To estimate the association of HIV symptoms with health-related quality of life and with disability days. Design: Prospective cohort study. Setting: HIV providers in 28 urban and 24 rural randomly selected sites throughout the United States. Patients: Nationally representative sample of 2267 adults with known HIV infection who were interviewed in 1996 and again between 1997 and 1998. Measurements: Symptoms, two single-item global measures of health-related quality of life (perceived health and perceived quality of life), and disability days. Results: White patches in the mouth; nausea or loss of appetite; persistent cough, difficulty breathing, or difficulty catching one's breath; and weight loss were associated with more disability days and worse scores on both health-related quality-of-life measures. Headache; pain in the mouth, lips, or gums; dry mouth; and sinus infection, pain, or discharge were associated with worse perceived health, Pain in the mouth, lips, or gums; trouble with eyes; pain, numbness, or tingling of hands or feet; and diarrhea or loose or watery stools were associated with worse perceived quality of life. Headache and fever, sweats, or chills were associated with more disability days. Conclusions: Several symptoms are associated with worse health-related quality of life and more disability days in persons with HIV infection. In such patients, targeting specific symptoms may improve health-related quality of life and reduce disability. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Div Gen Internal Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Lorenz, KA (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Div Gen Internal Med, 11303 Wilshire Blvd,Code 111-G, Los Angeles, CA 90073 USA. RI Hays, Ronald/D-5629-2013 FU AHRQ HHS [HS08578]; ASC OASH HHS [R01AS10227] NR 20 TC 99 Z9 102 U1 1 U2 10 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 MAY 1 PY 2001 VL 134 IS 9 SU S BP 854 EP 860 PN 2 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 429XK UT WOS:000168543100009 PM 11346321 ER PT J AU Xu, JW Nazzal, J Peretti, GM Kirchhoff, CH Randolph, MA Yaremchuk, MJ AF Xu, JW Nazzal, J Peretti, GM Kirchhoff, CH Randolph, MA Yaremchuk, MJ TI Tissue-engineered cartilage composite with expanded polytetrafluoroethylene membrane SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons CY SEP 14-16, 2000 CL MONTREAL, CANADA SP NE Soc Plast Surgeons ID CHONDROCYTES; RECONSTRUCTION; EAR; GRAFTS; MATRIX AB The authors report a new approach using expanded polytetrafluoroethylene (ePTFE) membrane as pseudoperichondrium to support engineered cartilage. Swine auricular chondrocytes were isolated and mixed with fibrin glue to achieve a final concentration of 40 x 10(6) cells per milliliter. The fibrin glue-cell suspension was assembled with ePTFE and the constructs were implanted into the dorsal subcutaneous pockets of nude mice for 12 weeks. Two experimental groups were prepared in this study: (1) ePTFE placed in the central part of the specimen in group 1 and (2) ePTFE placed on the outside surfaces in group 2, All specimens were subjected to histological and gross mechanical evaluation. Histological results showed neocartilage formation in both groups. The integration between neocartilage and ePTFE forms a tight bond. Gross mechanical testing revealed that the flexibility of specimens in group 2 were similar to that of native cartilage with intact perichondrium, whereas the flexibility of specimens in group 1 were poor. From these results the authors conclude that it is possible to produce a tissue-engineered cartilage framework using ePTFE as a support material to simulate the perichondrium. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg,Dept Plast Surg, Boston, MA 02114 USA. Shanghai Med Univ, Zhongshan Hosp, Dept Plast & Reconstruct Surg, Shanghai 200032, Peoples R China. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg,Dept Plast Surg, WAC 453,15 Parkman St, Boston, MA 02114 USA. RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 NR 21 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 2001 VL 46 IS 5 BP 527 EP 532 DI 10.1097/00000637-200105000-00012 PG 6 WC Surgery SC Surgery GA 431AZ UT WOS:000168610900022 PM 11352427 ER PT J AU Peretti, GM Randolph, MA Zaporojan, V Bonassar, LJ Xu, JW Fellers, JC Yaremchuk, MJ AF Peretti, GM Randolph, MA Zaporojan, V Bonassar, LJ Xu, JW Fellers, JC Yaremchuk, MJ TI A biomechanical analysis of an engineered cell-scaffold implant for cartilage repair SO ANNALS OF PLASTIC SURGERY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the Northeastern-Society-of-Plastic-Surgeons CY SEP 14-16, 2000 CL MONTREAL, CANADA SP NE Soc Plast Surgeons ID ARTICULAR-CARTILAGE; DEFECTS; MATRIX; MODEL AB This study evaluated the biomechanical and physical properties of newly formed cartilage engineered from isolated chondrocytes in combination with matrix components. Four groups of constructs were studied. Group A consisted of lyophilized articular cartilage chips mixed with a cell-fibrinogen solution and thrombin to obtain constructs made of fibrin glue, chondrocytes, and cartilage chips. Group B constructs were prepared using fibrin glue and cartilage chips without cells. Group C contained chondrocytes in fibrin glue without chips, and group D comprised constructs of fibrin glue alone. Specimens were implanted in the subcutaneous tissue of nude mice for 9 weeks. At necropsy the specimens were examined grossly, physically, biomechanically, and histologically, The original, preimplantation mass of the constructs was retained only in experimental group A. Histological analysis of specimens in experimental groups A and C demonstrated the presence of newly formed cartilaginous matrix, whereas only fibrotic tissue was observed in control groups B and D. Biomechanical analysis demonstrated higher mean values of equilibrium modulus in the experimental samples of group A with respect to all control groups. This study demonstrated that adding lyophilized cartilage chips to a fibrin glue-engineered cartilage construct maintains the biomechanical properties and the original mass after medium-/long-term in vivo transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Ctr Tissue Engn, Worcester, MA USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WACC 453,15 Parkman St, Boston, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016; Peretti, Giuseppe/K-6358-2016 OI Bonassar, Lawrence/0000-0003-1094-6433; Peretti, Giuseppe/0000-0001-9341-7187 FU NIAMS NIH HHS [R03 AR45059] NR 13 TC 49 Z9 54 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 2001 VL 46 IS 5 BP 533 EP 537 DI 10.1097/00000637-200105000-00013 PG 5 WC Surgery SC Surgery GA 431AZ UT WOS:000168610900024 PM 11352428 ER PT J AU Z'graggen, K Warshaw, AL Werner, J Graeme-Cook, F Jimenez, RE Castillo, CFD AF Z'graggen, K Warshaw, AL Werner, J Graeme-Cook, F Jimenez, RE Castillo, CFD TI Promoting effect of a high-fat/high-protein diet in DMBA-induced ductal pancreatic cancer in rats SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 112th Annual Meeting of the Southern-Surgical-Association CY DEC 04-06, 2000 CL PALM BEACH, FLORIDA SP SO Surg Assoc ID K-RAS MUTATIONS; EXOCRINE PANCREAS; COLON-CANCER; HIGH-FAT; CARCINOGENESIS; DNA; 7,12-DIMETHYLBENZ(A)ANTHRACENE; ADENOCARCINOMA; PROGRESSION; TUMORS AB Objective To investigate whether a high-fat/high-protein diet (HFPD) acts as a promoter of the natural course of cancer growth in the 7,12-dimethylbenzanthracene (DMBA)-induced ductal pancreatic cancer model in rats. Summary Background Data DMBA implantation to the rat pancreas induces ductal adenocarcinoma. Information regarding the effects of diet and the presence of K-ras mutation in this model is not available. Methods Rats were randomly assigned to regular rat chow or a diet with a 30% content in fat and protein (HFPD). The presentation of cancer, the histologic spectrum of neoplasia at 1 and 9 months, and the prevalence of cancer in relation to diet were assessed. Histologic specimens comprising normal ducts, hyperplasia, dysplasia/carcinoma in situ, or carcinoma were designated by a pathologist and microdissected. Genomic DNA was extracted. and K-ras and H-ras gene mutations were determined by a mutant-enriched polymerase chain reaction assay and direct sequencing. Results Rats fed HFPD increased their weight significantly compared with controls. DMBA induced characteristic stages of neoplasia at the implant site but not elsewhere. Macroscopic cancers of the pancreatic head presented regularly with common bile duct and gastric outlet obstruction. The prevalence of K-ras mutations was proportional to the degree of epithelial abnormality. K-ras mutations were significantly more frequent in cancer than in normal and hyperplastic ducts. H-ras mutations were not found. At 1 month in the HFPD-fed rats, the prevalence of cancer (16%) and dysplasia (16%) was not significantly different from the prevalence of cancer (29%) and dysplasia (8%) in the chow-fed rats. At 9 months the prevalence of cancer in the HFPD-fed rats increased to 29%, whereas that in the chow-fed rats decreased to 17%. The combined prevalence of cancer and dysplasia at 9 months in the HFPD-fed rats (34%) significantly exceeded that in the chow-fed rats. Conclusions DMBA induces characteristic stages of neoplasia in the evolution of ductal pancreatic cancer in rats. K-ras mutations occur progressively in the ladder of oncogenesis, as in human pancreatic neoplasms. The addition of a diet with a high fat and protein content acts as a promoter of carcinogenesis, possibly by interfering with repair mechanisms and natural regression of early lesions. C1 Massachusetts Gen Hosp, Dept Surg, WACC 336, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, WACC 336, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Castillo, CFD (reprint author), Massachusetts Gen Hosp, Dept Surg, WACC 336, Boston, MA 02114 USA. NR 21 TC 19 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 2001 VL 233 IS 5 BP 688 EP 694 DI 10.1097/00000658-200105000-00013 PG 7 WC Surgery SC Surgery GA 428NJ UT WOS:000168467500024 PM 11323507 ER PT J AU Wain, JC Kaiser, LR Johnstone, DW Yang, SC Wright, CD Friedberg, JS Feins, RH Heitmiller, RF Mathisen, DJ Selwyn, MR AF Wain, JC Kaiser, LR Johnstone, DW Yang, SC Wright, CD Friedberg, JS Feins, RH Heitmiller, RF Mathisen, DJ Selwyn, MR TI Trial of a novel synthetic sealant in preventing air leaks after lung resection SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 31-FEB 02, 2000 CL FT LAUDERDALE, FLORIDA SP Soc Thorac Surg ID FIBRIN GLUE; LOBECTOMY AB Background. Postoperative air leaks are a major cause of morbidity after lung resections. This study was designed to evaluate the efficacy and safety of a new synthetic, bioresorbable surgical sealant in preventing air leaks after pulmonary resection. Methods. In a multicenter trial, 172 patients undergoing thoracotomy were randomized intraoperatively in a 2:1 ratio to receive surgical sealant applied to sites at risk for air leak after standard methods of lung closure (treatment group) or to have standard lung closure only (control group). The primary outcome variable was the percentage of patients free of air leakage throughout hospitalization. Secondary outcome variables were the control of air leaks intraoperatively and the time to postoperative air leak cessation. Time to chest tube removal, time to hospital discharge, and safety outcomes were also evaluated. Results. Air leaks were identified before randomization in 89 of 117 patients in the treatment group and in 39 of 55 patients in the control group. Application of the sealant resulted in control of air leaks in 92% of treated patients (p less than or equal to 0.001). A significantly higher percentage of treated patients than control patients remained free of air leaks during hospitalization (39% versus 11%, p less than or equal to 0.001). The mean times to last observable air leak were 30.9 hours in the treatment group and 52.3 hours in the control group (p = 0.006). In the treatment group, trends were observed for reduced time to chest tube removal and earlier discharge. No significant difference was identified in postoperative morbidity and mortality between the two groups. Conclusions. Air leaks after lung resection occur in most patients. The application of this novel surgical sealant appears to be effective and safe in preventing postoperative air leaks. (Ann Thorac Surg 2001;71:1623-9) (C) 2001 by The Society of Thoracic Surgeons. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Thorac Surg,Div Gen Thorac Surg, Boston, MA 02114 USA. Univ Rochester, Strong Mem Hosp, Med Ctr, Dept Cardiothorac Surg, Rochester, NY 14642 USA. Hosp Univ Penn, Dept Gen Thorac Surg, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Div Thorac Surg, Baltimore, MD USA. Stat Unltd, Savannah, GA USA. RP Wain, JC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Thorac Surg,Div Gen Thorac Surg, Balke 1570,55 Fruit St, Boston, MA 02114 USA. NR 13 TC 84 Z9 86 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2001 VL 71 IS 5 BP 1623 EP 1629 DI 10.1016/S0003-4975(01)02537-1 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 433AZ UT WOS:000168734300040 PM 11383811 ER PT J AU Dinh, MHT Galvin, JM Aretz, TH Torchiana, DF AF Dinh, MHT Galvin, JM Aretz, TH Torchiana, DF TI Left ventricular hamartoma associated with ventricular tachycardia SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID MATURE CARDIAC MYOCYTES AB Cardiac hamartomas are a rare type of benign tumor affecting the heart. We describe a 33-year-old patient who presented with a wide complex tachycardia. Diagnostic imaging revealed a mass in the patient's left ventricular wall, near the apex of the heart. The mass was surgically resected and appeared benign. Its pathology was that of a hamartoma of mature cardiac myocytes. Postoperative electrophysiology evaluation showed no inducible focus and the patient remains alive and asymptomatic after 2 years of follow-up. (Ann Thorac Surg 2001;71:1673-5) (C) 2001 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Electrophysiol, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Massachusetts Gen Hosp, Dept Cardiac Surg, 55 Fruit St, Boston, MA 02114 USA. NR 12 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 2001 VL 71 IS 5 BP 1673 EP 1675 DI 10.1016/S0003-4975(00)02312-2 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 433AZ UT WOS:000168734300050 PM 11383821 ER PT J AU Barchiesi, F Schimizzi, AM Najvar, LK Bocanegra, R Caselli, F Di Cesare, S Giannini, D Di Francesco, LF Giacometti, A Carle, F Scalise, G Graybill, JR AF Barchiesi, F Schimizzi, AM Najvar, LK Bocanegra, R Caselli, F Di Cesare, S Giannini, D Di Francesco, LF Giacometti, A Carle, F Scalise, G Graybill, JR TI Interactions of posaconazole and flucytosine against Cryptococcus neoformans SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AMPHOTERICIN-B; COMBINATION THERAPY; MURINE MODEL; IN-VITRO; INVASIVE ASPERGILLOSIS; FUNGICIDAL ACTIVITY; FLUCONAZOLE; MENINGITIS; ITRACONAZOLE; CANDIDIASIS AB A checkerboard methodology, based on standardized methods proposed by the National Committee for Clinical Laboratory Standards for broth microdilution antifungal susceptibility testing, was applied to study the in vitro interactions of flucytosine (FC) and posaconazole (SCH 56592) (FC-SCH) against 15 isolates of Cryptococcus neoformans, Synergy, defined as a fractional inhibitory concentration (FIC) index of <0.50, was observed for 33% of the isolates tested. When synergy was not achieved, there was still a decrease in the MIC of one or both drugs when they were used in combination. Antagonism, defined as a FIC of >4.0, was not observed. The in vitro efficacy of combined therapy was confirmed by quantitative determination of the CFU of C, neoformans 486, an isolate against which the FC-SCH association yielded a synergistic interaction. To investigate the potential beneficial effects of this combination therapy in vivo, we established two experimental murine models of cryptococcosis by intracranial or intravenous injection of cells of C. neoformans 486. At 1 day postinfection, the mice were randomized into different treatment groups. One group each received each drug alone, and one group received the drugs in combination, While combination therapy was not found to be significantly more effective than each single drug in terms of survival, tissue burden experiments confirmed the potentiation of antifungal activity with the combination. Our study demonstrates that SCH and FC combined are significantly more active than either drug alone against C. neoformans in vitro as well in vivo. These findings suggest that this therapeutic approach could be useful in the treatment of cryptococcal infections. C1 Univ Ancona, Ctr Interdipartimentale Epidemiol Biostat & Infor, Ancona, Italy. Univ Ancona, Ist Malattie Infett & Med Pubbl, Ancona, Italy. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Austin, TX USA. RP Barchiesi, F (reprint author), Azienda Osped Umberto 1, Ist Malattie Infectt & Med Pubbl, Via Conca Torrette, I-60020 Ancona, Italy. NR 29 TC 28 Z9 36 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 2001 VL 45 IS 5 BP 1355 EP 1359 DI 10.1128/AAC.45.5.1355-1359.2001 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 424PH UT WOS:000168240300006 PM 11302795 ER PT J AU LaBranche, CC Galasso, G Moore, JP Bolognesi, DP Hirsch, MS Hammer, SM AF LaBranche, CC Galasso, G Moore, JP Bolognesi, DP Hirsch, MS Hammer, SM TI HIV fusion and its inhibition SO ANTIVIRAL RESEARCH LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; SMALL-MOLECULE INHIBITOR; SYNCYTIUM-INDUCING PHENOTYPE; GP41 CORE STRUCTURE; MEMBRANE-FUSION; RECEPTOR-BINDING; IN-VIVO; TYPE-1 INFECTION; MONOCLONAL-ANTIBODIES C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Macrae Grp, Rockville, MD USA. Cornell Univ, Weill Med Coll, New York, NY USA. Trimeris Inc, Durham, NC USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP LaBranche, CC (reprint author), Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NR 130 TC 102 Z9 106 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2001 VL 50 IS 2 BP 95 EP 115 DI 10.1016/S0166-3542(01)00130-9 PG 21 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 444GQ UT WOS:000169392100001 PM 11369431 ER PT J AU Liyanage, H Kashket, S Young, M Kashket, ER AF Liyanage, H Kashket, S Young, M Kashket, ER TI Clostridium beijerinckii and Clostridium difficile detoxify methylglyoxal by a novel mechanism involving glycerol dehydrogenase SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; IN-VIVO; SOLVENT PRODUCTION; MAILLARD REACTION; ACETOBUTYLICUM; PROTEIN; GLUTATHIONE; PATHWAY; GROWTH; 1,2-PROPANEDIOL AB In contrast to gram-negative bacteria, little is known about the mechanisms by which gram-positive bacteria degrade the toxic metabolic intermediate methylglyoxal (MG). Clostridium beijerinckii BR54, a Tn1545 insertion mutant of the NCIMB 8052 strain, formed cultures that contained significantly more (free) h-lc than wild-type cultures, Moreover, BR54 was more sensitive to growth inhibition by added MG than the wild type, suggesting that it has a reduced ability to degrade MG. The single copy of Tn1545 in this strain lies just downstream from gldA, encoding glycerol dehydrogenase. As a result of antisense RN;I production, cell extracts of BR54 possess significantly less glycerol dehydrogenase activity than wild-type cell extracts (H, Liyanage, ill, Young, and E, R, Kashket, J, Mel. Microbiol. Biotechnol, 2:87-93, 2000), Inactivation of gldA in both C, beijerinckii and Clostridium difficile gave rise to pinpoint colonies that could not be subcultured, indicating that glycerol dehydrogenase performs an essential function in both organisms. We propose that this role is detoxification of MG. To our knowledge, this is the first report of targeted gene disruption in the C. difficile chromosome. C1 Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. Forsyth Inst, Boston, MA 02115 USA. Univ Wales, Inst Biol Sci, Aberystwyth SY23 3DD, Dyfed, Wales. RP Kashket, ER (reprint author), Boston Univ, Sch Med, Dept Microbiol, 715 Albany St, Boston, MA 02118 USA. NR 44 TC 29 Z9 31 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAY PY 2001 VL 67 IS 5 BP 2004 EP 2010 DI 10.1128/AEM.67.5.2004-2010.2001 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 428YC UT WOS:000168488400003 PM 11319074 ER PT J AU North, PE Waner, M Mizeracki, A Mrak, RE Nicholas, R Kincannon, J Suen, JY Mihm, MC AF North, PE Waner, M Mizeracki, A Mrak, RE Nicholas, R Kincannon, J Suen, JY Mihm, MC TI A unique microvascular phenotype shared by juvenile hemangiomas and human placenta SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 13th International Workshop on Vascular Anomalies CY MAY 10, 2000 CL MONTREAL, CANADA ID CONGENITAL MUSCULAR-DYSTROPHY; ENDOTHELIAL GROWTH-FACTOR; GLUCOSE TRANSPORTER GLUT-1; MONOCLONAL-ANTIBODY; ANTIGEN EXPRESSION; MEROSIN DEFICIENCY; TERM PLACENTA; LAMININ; CELLS; APOPTOSIS AB Background: Juvenile hemangiomas are common, benign tumors, distinctive for their perinatal presentation, rapid growth during the first year of life, and subsequent involution. We recently reported that endo thelia of hemangiomas highly express GLUT1, a glucose transporter normally restricted to endothelia with blood-tissue barrier function, as in brain and placenta. Objective: To investigate possible further similarities between hemangioma and placental vessels. Design: In a retrospective study of a variety of vascular tumors and anomalies, we assessed lesional immunoreactivities for the placenta-associated vascular antigens Fc gamma RII, Lewis Y antigen (LeY), merosin, and GLUT1. Setting: A university-affiliated pediatric hospital. Main Outcome Measure: Immunoreactivities scored for each antigen were summarized according to lesional type, compared with those of normal skin, brain, and placenta, and correlated with patient age, sex, and lesional location. Results: All of 66 hemangiomas (patients aged 22 days to 7 years) showed intense immunoreactivity for Fc gamma RII, merosin, LeY, and GLUT1. No immunoreactivities for these markers were seen in any of 26 vascular malformations, 4 granulation tissue specimens, 13 pyogenic granulomas, or in the tumor vasculature of 6 malignant tumors of nonvascular origin. Microvascular immunoreactivity for all 4 markers was observed in placental chorionic villi, but was absent in microvessels of normal skin and subcutis. Brain microvessels expressed only GLUT1 and merosin. Conclusions: A distinct constellation of tissue-specific markers is uniquely coexpressed by hemangiomas and placental microvessels. These findings imply a unique relationship between hemangioma and the placenta and suggest new hypotheses concerning the origin of these tumors. C1 Arkansas Childrens Hosp, Dept Pediat Pathol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Otolaryngol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Orthoped Surg, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Dermatol, Little Rock, AR 72205 USA. Dept Vet Affairs Med Ctr, Little Rock, AR USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP North, PE (reprint author), Arkansas Childrens Hosp, Dept Pediat Pathol, 800 Marshall St, Little Rock, AR 72202 USA. NR 58 TC 209 Z9 234 U1 0 U2 5 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 MAY PY 2001 VL 137 IS 5 BP 559 EP 570 PG 12 WC Dermatology SC Dermatology GA 434JY UT WOS:000168812400003 PM 11346333 ER PT J AU Bartzokis, G Beckson, M Lu, PH Nuechterlein, KH Edwards, N Mintz, J AF Bartzokis, G Beckson, M Lu, PH Nuechterlein, KH Edwards, N Mintz, J TI Age-related changes in frontal and temporal lobe volumes in men - A magnetic resonance imaging study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID BRAIN MORPHOLOGY; GRAY-MATTER; IN-VIVO; CEREBRAL-CORTEX; WHITE-MATTER; MRI; CHILDHOOD; ADOLESCENCE; HIPPOCAMPUS; MYELINATION AB Background? Imaging and postmortem studies provide converging evidence that, beginning in adolescence, gray matter volume declines linearly until old age, while cerebrospinal fluid volumes are stable in adulthood (age 20-50 years). Given the fixed volume of the cranium in adulthood, it is surprising that most studies observe no white matter volume expansion after approximately age 20 years. We examined the effects of the aging process on the frontal and temporal lobes. Methods: Seventy healthy adult men aged 19 to 76 years underwent magnetic resonance imaging. Coronal images focused on the frontal and temporal lobes were acquired using pulse sequences that maximized gray vs white matter contrast. The volumes of total frontal and temporal lobes as well as the gray and white matter subcomponents were evaluated. Results: Age-related linear loss in gray matter volume in both frontal(r=-0.62, P<.001) and temporal (r=-0.48, P<.001) lobes was confirmed. However, the quadratic function best represented the relationship between age and white matter volume in the frontal (P<.001) and temporal (P<.001) lobes. Secondary analyses indicated that white matter volume increased until age 44 years for the frontal lobes and age 47 years for the temporal lobes and then declined. Conclusions: The changes in white matter suggest that the adult brain is in a constant state of change roughly defined as periods of maturation continuing into the fifth decade of life followed by degeneration. Pathological states that interfere with such maturational processes could result in neurodevelopmental arrests in adulthood. C1 Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. Cent Arkansas Vet healthcare Syst, Mental Hlth Serv Line, Little Rock, AR USA. Greater Los Angeles VA Healthcare Syst, W Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. RP Bartzokis, G (reprint author), Cent Arkansas Vet Healthcare Syst, 2200 Ft Roots Dr,Bldg 170 116A-NLR, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 FU NIDA NIH HHS [1YO1 DA 50038]; NIMH NIH HHS [MH-37705, MH-51928] NR 31 TC 375 Z9 383 U1 1 U2 10 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 MAY PY 2001 VL 58 IS 5 BP 461 EP 465 DI 10.1001/archpsyc.58.5.461 PG 5 WC Psychiatry SC Psychiatry GA 428UE UT WOS:000168479100005 PM 11343525 ER PT J AU Letko, E Stechschulte, SU Kenyon, KR Sadeq, N Romero, TR Samson, CM Nguyen, QD Harper, SL Primack, JD Azar, DT Gruterich, M Dohlman, CH Baltatzis, S Foster, CS AF Letko, E Stechschulte, SU Kenyon, KR Sadeq, N Romero, TR Samson, CM Nguyen, QD Harper, SL Primack, JD Azar, DT Gruterich, M Dohlman, CH Baltatzis, S Foster, CS TI Amniotic membrane inlay and overlay grafting for corneal epithelial defects and stromal ulcers SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BASEMENT-MEMBRANE; SURFACE RECONSTRUCTION; OCULAR SURFACE; TRANSPLANTATION; EXPRESSION; DIFFERENTIATION; ULCERATION; CELLS; COLLAGEN; SURGERY AB Objectives: To determine the effect of amniotic membrane transplantation (AMT) on persistent corneal epithelial defects (PEDs) and to compare the efficacy between inlay and overlay techniques. Methods: Thirty patients (30 eyes) underwent AMT for FED. The use of AMT was restricted to patients in whom all previous measures, including bandage contact lens and tarsorrhaphy, had failed. The amniotic membrane was placed on the surface of the cornea in overlay (group A) or inlay (group B) fashion. Results: The FED healed after the first AMT in 21 eyes (70%) within an average of 25.5 days after surgery and recurred in 6 eyes (29%). Among the 22 eyes treated with an overlay AMT (group A), the FED healed after the first AMT in 14 eyes (64%) within an average of 24.5 days and recurred in 4 eyes (29%). Among the 8 eyes treated with an inlay AMT (group B), the FED healed within an average of 27.4 days after AMT, which did not statistically significantly differ from group A (P = .72). The FED healed after the first AMT in 7 eyes (88%) and recurred in 2 (29%) of 7 eyes. Conclusions: The AMT can be helpful in the treatment of FED in which all other conventional management has failed. However, the success rate in our study was not as high as that previously reported, and our results showed a high incidence of recurrences of epithelial defects. We did not find any difference between overlay and inlay techniques in terms of healing time and recurrence rate. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA USA. Cornea Consultants, Boston, MA USA. Univ Munich, Augenklin, D-8000 Munich, Germany. IBN Sina Hosp, Al Bahar Ophthalmol Ctr, Safat, Kuwait. Univ Athens, Gen Hosp, Sch Med, Eye Clin, Athens, Greece. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Serv Immunol, 243 Charles St, Boston, MA 02114 USA. NR 37 TC 73 Z9 81 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 2001 VL 119 IS 5 BP 659 EP 663 PG 5 WC Ophthalmology SC Ophthalmology GA 429KF UT WOS:000168515400002 PM 11346392 ER PT J AU Weymuller, EA Alsarraf, R Yueh, B Deleyiannis, FWB Coltrera, MD AF Weymuller, EA Alsarraf, R Yueh, B Deleyiannis, FWB Coltrera, MD TI Analysis of the performance characteristics of the University of Washington Quality of Life instrument and its modification (UW-QOL-R) SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID OF-LIFE; NECK-CANCER; HEAD; DEPRESSION AB Background: During a 5-year period, we analyzed 3 patient subsets from the University of Washington Quality of Life (UW-QOL) Registry and published the results. In each instance, editorial review has raised legitimate concerns regarding the UW-QOL instrument that deserve public comment. We present our response to these criticisms. Since our original publication (1993), we have added domains to the original UW-QOL instrument. These additions reflected our concern that we might be missing important elements in the spectrum of disease-specific response to treatment. Using the data we have accumulated in the last 5 years, we present an analysis of the internal consistency of the UW-QOL. We have identified those domains that are responsive (or not responsive) to treatment effect and have revised the UW-QOL accordingly to create the UW-QOL-R, which is recommended for future use. Design: The project began January 1, 1993, after approval by the UW Human Subjects Committee. Critical comments offered by external review were collated and responded to. Internal consistency was evaluated by interitem correlation matrix (Cronbach alpha) testing. Subjects: All new patients presenting to the UW Medical Center (Seattle) with a diagnosis of head and neck cancer were asked to participate in a prospective analysis of QOL changes during and after treatment. Intervention: Patients completed the pretreatment QOL questionnaire on the day of their initial workup. The format for the pretreatment test was an interviewer-supervised self-administered test; the subsequent tests were self-administered and were completed at 3, 6, 12, 24, and 36 months. Other data entered for each patient included site, stage, treatment, histologic classification, reconstruction, and current status. A QOL registrar was responsible for patient follow-up, data collection, and collation. All data were entered into the departmental relational database. Results: Criticisms by external review included the following: "it is improper to call it [UW-QOL] a measure of quality of life"; "the summary scale is problematic because it implies that each of the subscales are weighted or 'valued' equally"; "some domain questions relate to surgery specific issues...while others are specific to radiation";"we were confused by the scoring"; and "the UW-QOL index does not specifically address the psychological impact of the disease and its treatment." After evaluation of internal consistency, the UW-QOL was modified by removing 2 domains that correlated poorly with the others. This resulted in a 10-item instrument (UW-QOL-R) with an overall internal consistency score of 0.85. Conclusions: The UW-QOL can be effectively and accurately used to compare treatment effects in the management of head and neck cancer. With this revised instrument, the 10 items appear to measure the domains of overall QOL in a highly consistent and reliable fashion over time. C1 Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. RP Weymuller, EA (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, Box 356515, Seattle, WA 98195 USA. OI Yueh, Bevan/0000-0003-1380-1053 NR 12 TC 106 Z9 107 U1 0 U2 3 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 MAY PY 2001 VL 127 IS 5 BP 489 EP 493 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 429KC UT WOS:000168515000001 PM 11346422 ER PT J AU Cooper, RA Fitzgerald, SG Boninger, ML Prins, K Rentschler, AJ Arva, J O'Connor, TJ AF Cooper, RA Fitzgerald, SG Boninger, ML Prins, K Rentschler, AJ Arva, J O'Connor, TJ TI Evaluation of a pushrim-activated, power-assisted wheelchair SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE activities of daily living; ergonomics; rehabilitation; wheelchairs ID MANUAL WHEELCHAIRS; PROPULSION; EFFICIENCY; RESPONSES AB Objective: To evaluate a novel pushrim-activated, power-assisted wheelchair (PAPAW) for compliance with wheelchair standards, metabolic energy cost during propulsion, and ergonomics during selected activities of daily living (ADLs). Design: A 3-phase study, the second and third of which were repeated-measures designs. Setting: A rehabilitation engineering center within a Veterans Affairs medical center. Patients: Eleven full-time, community-dwelling, manual wheelchair users (4 women, 6 men) with spinal cord injuries or multiple sclerosis. Interventions: Phase 1: Compliance testing, with a test dummy, in accordance with the wheelchair standards of the American National Standards Institute and the Rehabilitation Engineering and Assistive Technology Society of North America. Phase 2: Metabolic energy consumption testing-at 2 speeds and 3 resistance levels-in subjects' manual wheelchair and the PAPAW. Phase 3. Evaluation of ability to perform ADLs and ergonomics of the PAPAW compared with the subjects personal wheelchair. Main Outcome Measures: Phase 1. The PAPAW's static stability, static strength, impact strength, fatigue strength, environmental response, obstacle climbing ability, range, maximum speed, and braking distance. Phase 2. Subjects' oxygen consumption per minute, minute ventilation, and heart rate during different speeds and workloads with a PAPAW and their own wheelchairs. Phase 3: Subject ratings of perceived comfort and basic ergonomics while performing selected ADLs. Completion time, stroke frequency, and heart rate during each ADL. Results: Phase 1: The PAPAW was found to be in compliance with wheelchair standards. Phase 2: With the PAPAW, the user had a significantly lower oxygen consumption ((V) over dotO(2)mL/min: p < .0001; (V) over dotO(2)mL/kg x min: p < .0001) and heart rate (p < .0001) when compared with a manual wheelchair at different speeds. Phase 3: The PAPAW had a significantly higher mean ergonomic evaluation (p < .01) than the subjects' personal wheelchairs. The results of comparing the ratings of the car transfer between the PAPAW and the subjects' personal wheelchair showed a significant difference in the task of taking the wheels off (p < .001) and putting the wheels back on (p = .001), with the PAPAW receiving lower ratings. Conclusion: This study indicated that the PAPAW is compliant with wheelchair standards, reduces the energy demand placed on the user during propulsion, and that subjects rated its ergonomics favorably when compared with their personal wheelchair. PAPAWs may provide manual wheelchairs with a less physiologically stressful means of mobility with few adaptations to the vehicle or home environment. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1, VA REhabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1, VA REhabil Res & Dev Ctr, 7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 25 TC 49 Z9 51 U1 2 U2 13 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 MAY PY 2001 VL 82 IS 5 BP 702 EP 708 DI 10.1053/apmr.2001.20836 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 429RR UT WOS:000168531200025 PM 11346854 ER PT J AU Bilimoria, MM Lauwers, GY Doherty, DA Nagorncy, DM Belghiti, J Do, KA Regimbeau, JM Ellis, LM Curley, SA Ikai, I Yamaoka, Y Vauthey, JN AF Bilimoria, MM Lauwers, GY Doherty, DA Nagorncy, DM Belghiti, J Do, KA Regimbeau, JM Ellis, LM Curley, SA Ikai, I Yamaoka, Y Vauthey, JN TI Underlying liver disease, not tumor factors, predicts long-term survival alter resection of hepatocellular carcinoma SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 108th Scientific Session of the Western-Surgical-Association CY NOV 13-14, 2000 CL DANA POINT, CALIFORNIA SP Western Surg Assoc ID CHRONIC ACTIVE HEPATITIS; PROGNOSTIC FACTORS; CLINICOPATHOLOGICAL FEATURES; CIRRHOSIS; HEPATECTOMY; RECURRENCE; SURGERY; ALPHA AB Hypothesis: A subset of patients can be identified who will survive without recurrence beyond 5 years after hepatic resection for hepatocellular carcinoma (HCC). Design: A retrospective review of a multi-institutional database of 591 patients who had undergone hepatic resection for HCC and on-site reviews of clinical records and pathology slides. Setting: All patients had been treated in academic referral centers within university-based hospitals. Patients: We identified 145 patients who had survived for 5 years or longer after hepatic resection for HCC. Main Outcome Measures: Clinical and pathologic factors, as well as scoring of hepatitis and fibrosis in the surrounding liver parenchyma, were assessed for possible association with survival beyond 5 years and cause of death among the 145 five-year survivors. Results: Median additional survival duration longer than 5 years was 4.1 years. Women had significantly longer median additional survival durations than did men (81 months vs 38 months, respectively, after the 5-year mark) (P=.008). Surgical margins, type of resection, an elevated preoperative alpha -fetoprotein level, and the presence of multiple tumors or microscopic vascular invasion had no bearing on survival longer than 5) ears. However, patients who survived for 5 years who also had normal underlying liver or minimal fibrosis (score, 0-2) at surgery had significantly longer additional survival than did patients with moderate fibrosis (score, 3-4) or severe fibrosis/cirrhosis (score, 5-6) (P < .001). Conclusions: Death caused by HCC is rare beyond 5) ears after resection of I-ICC in the absence of fibrosis or cirrhosis. The data suggest that chronic liver disease acts as a field of cancerization contributing to new HCC. These patients may benefit from therapies directed at the underlying liver disease. C1 Univ Texas, MD Anderson Canc Ctr, Int Cooperat Study Grp Hepatocellular Carinoma, Dept Surg Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Int Cooperat Study Grp Hepatocellular Carinoma, Dept Biostat, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Mayo Clin, Dept Surg, Rochester, MN USA. Hop Beaujon, Dept Surg, Paris, France. Kyoto Univ, Grad Sch Med, Dept Surg, Kyoto, Japan. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Int Cooperat Study Grp Hepatocellular Carinoma, Dept Surg Oncol, 1515 Holcombe Blvd,Box 106, Houston, TX 77030 USA. NR 32 TC 122 Z9 134 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 2001 VL 136 IS 5 BP 528 EP 534 DI 10.1001/archsurg.136.5.528 PG 7 WC Surgery SC Surgery GA 428PZ UT WOS:000168471200009 PM 11343543 ER PT J AU James, JA Neas, BR Moser, KL Hall, T Bruner, GR Sestak, AL Harley, JB AF James, JA Neas, BR Moser, KL Hall, T Bruner, GR Sestak, AL Harley, JB TI Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATOID-ARTHRITIS; PEPTIDE IMMUNIZATION; REVISED CRITERIA; SM B/B'; INFECTION; CLASSIFICATION; AUTOIMMUNITY; SERA AB Objective. The possible molecular mimicry of the Epstein-Barr virus (EBV) peptide PPPGRRP by the peptide PPPGMRPP from Sm B'/B of the human spliceosome is consistent with the possibility that EBV infection is related to the origin of systemic lupus erythematosus (SLE) in some patients. Association of EBV exposure with SLE was therefore tested for and subsequently found in children and adolescents (odds ratio [OR] 49.9, 95% confidence interval [95% CI] 9.3-1,025, P < 10(-11)). These results were confirmed at the level of EBV DNA (OR > 10, 95% CI 2.53-infinity, P < 0.002). Much smaller seroconversion rate differences were found against 4 other herpes viruses. Herein, we extend these studies to adults and test the hypothesis that EBV infection is associated with adult SLE. Methods. We selected 196 antinuclear antibody-positive adult SLE patients (age 20 years) and 2 age-, race-, and sex-matched controls per patient. SLE patients and matched controls were tested for evidence of previous infection with EBV, cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), or varicella-zoster virus (VZV) by standardized enzyme-linked immunosorbent assays. Results. Of the 196 lupus patients tested, all but 1 had been exposed to EBV, while 22 of the 392 controls did not have antibodies consistent with previous EBV exposure (OR 9.35, 95% Cl 1.45-infinity, P = 0.014). No differences were observed between SLE patients and controls in the seroconversion rate against CMV, HSV-2, or VZV. Conclusion. These new data from adults, along with the many suggestive features of EBV infection, are consistent with the contribution of this infection to the etiology of SLE. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. US Dept Vet Affairs, Oklahoma City, OK USA. RP James, JA (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAID NIH HHS [AI-31584]; NIAMS NIH HHS [AR-01981, AR-42474] NR 20 TC 185 Z9 194 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 MAY PY 2001 VL 44 IS 5 BP 1122 EP 1126 DI 10.1002/1529-0131(200105)44:5<1122::AID-ANR193>3.0.CO;2-D PG 5 WC Rheumatology SC Rheumatology GA 485JJ UT WOS:000171751000018 PM 11352244 ER PT J AU Elangovan, L Shinaberger, CS Kraut, JA Shinaberger, AH AF Elangovan, L Shinaberger, CS Kraut, JA Shinaberger, AH TI HEMO equilibrated Kt/V coals are difficult to achieve in large male patients SO ASAIO JOURNAL LA English DT Article ID UREA REDUCTION RATIO; HEMODIALYSIS-PATIENTS; CARDIOPULMONARY RECIRCULATION; DIALYSIS; MORTALITY; SURVIVAL; EFFICIENCY; MORBIDITY; WEIGHT AB The long-term outcome of chronic hemodialysis patients is influenced by the adequacy of dialysis treatment. A major objective of the ongoing US HEMO Study is to determine ii a higher target value of treatment as measured by the equilibrated Kt/V (eKt/V), a calculation of dialysis adequacy developed for the study, of 1.45 results in a better outcome than the presently accepted target value for eKt/V of 1.05 (approximately equal to spKt/V of 1.2). eKt/V corrects for urea rebound and gives a better estimate of actual treatment received. To examine the feasibility of achieving the higher eKt/V in large hemodialysis patients, a retrospective analysis of 389 monthly eKt/V values from 65 men on chronic hemodialysis of larger than average size dialyzed at high blood and dialysate flows (QB 400, QD 800 ml/min) with large dialyzers (1.8-2.2 m(2)) for longer than 4 hours three times weekly was performed. A total of 278 treatments considered optimal by a blood water urea clearance estimate were included in the final analyses. The mean body weight and Chertow water volume were 84.3 +/- 16.5 kgm and 50.0 +/- 6.7 L, respectively. The mean sp Kt/V was 1.29 +/- 0.17. The mean eKt/V was 1.16 +/- 0.14 and was inversely correlated with weight and water volume (p < 0.0001). Despite the large dialyzers and high blood and dialysate flow rates, no patient weighing more than 80 kgm or with body water volume exceeding 46 liters achieved an eKt/V of 1.45. This study suggests that creative dialyses will be required to achieve the HEMO "high arm" target in large patients. C1 W Los Angeles VA Hlth Care Ctr, Nephrol Sect 111L, Med Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Hlth, Div Epidemiol, Los Angeles, CA 90024 USA. RP Shinaberger, AH (reprint author), W Los Angeles VA Hlth Care Ctr, Nephrol Sect 111L, Med Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 33 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD MAY-JUN PY 2001 VL 47 IS 3 BP 235 EP 239 DI 10.1097/00002480-200105000-00015 PG 5 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 431HQ UT WOS:000168626100012 PM 11374764 ER PT J AU Huang, Y Song, LX Wu, S Fan, F Lopes-Virella, MF AF Huang, Y Song, LX Wu, S Fan, F Lopes-Virella, MF TI Oxidized LDL differentially regulates MMP-1 and TIMP-1 expression in vascular endothelial cells SO ATHEROSCLEROSIS LA English DT Article DE oxidized LDL; metalloproteinases; tissue inhibitor of metalloproteinases; endothelium ID LOW-DENSITY-LIPOPROTEIN; GROWTH-FACTOR EXPRESSION; HUMAN CORONARY-ARTERIES; TISSUE INHIBITOR; HUMAN-FIBROBLASTS; POSTTRANSCRIPTIONAL REGULATION; OXIDATIVE MODIFICATION; GENE-EXPRESSION; COLLAGENASE; METALLOPROTEINASES AB We have reported recently that oxidized low-density lipoprotein (oxLDL) stimulates matrix metalloproteinase-1 (MMP-1) expression in human vascular endothelial cells. Thr: present study was conducted to examine the effect of oxLDL on expression of Tissue inhibitor of metalloproteinase-1 (TIMP-1), an endogenous inhibitor of MMPs, in human vascular endothelial cells. Our enzyme-linked immunosorbent assay and Northern blot analysis showed that oxLDL inhibited TIMP-1 secretion and expression by human umbilical vein endothelial cells. In contrast. PMA stimulated TIMP-1 expression and secretion. Both oxLDL and PMA increased MMP-1 expression and secretion significantly as previously reported. Inhibition by oxLDL of TIMP-1 expression was also observed in human aortic endothelial cells. Collagenase activity as detected by an enzymatic activity assay demonstrated, as expected, an increase in collagenase activity in the culture medium from oxLDL-treated cells as compared with that from untreated cells. The presented data indicates that oxLDL differentially regulates TIMP-1 and MMP-1 expression, whereas PMA coordinately regulates TIMP-1 and MMP-1 in vascular endothelial cells. The lack of coordination in the secretion of MMP-1 and TIMP-1 induced by oxLDL leads to an increased collagen-degrading activity that may contribute to destabilization of atherosclerotic plaques. Published by Elsevier Science Ireland Ltd. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29401 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 114 Doughty St, Charleston, SC 29403 USA. FU NHLBI NIH HHS [HL-55782] NR 32 TC 35 Z9 39 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD MAY PY 2001 VL 156 IS 1 BP 119 EP 125 DI 10.1016/S0021-9150(00)00638-9 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 438BU UT WOS:000169034500014 PM 11369004 ER PT J AU Suter, J Hendry, IR Ndjountche, L Obholz, K Pru, JK Davis, JS Rueda, BR AF Suter, J Hendry, IR Ndjountche, L Obholz, K Pru, JK Davis, JS Rueda, BR TI Mediators of interferon gamma-initiated signaling in bovine luteal cells SO BIOLOGY OF REPRODUCTION LA English DT Article DE corpus luteum; corpus luteum function; cytokines; signal transduction ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; GRANULOSA-CELLS; FACTOR-ALPHA; SYNTHETIC CAPACITY; CORPUS-LUTEUM; IFN-GAMMA; ACTIVATION; INDUCTION; EXPRESSION AB Interferon gamma (IFN gamma) has been implicated as a mediator of luteal steroidogenesis and cell fate. IFN gamma -initiated signaling events, although implied by studies in cell lines, have yet to be described in primary luteal cells. The objective of these studies was to begin to characterize IFN gamma -initiated signaling within luteal cells. Dispersed bovine luteal cell cultures were challenged with increasing levels of bovine recombinant IFN gamma (0-1000 U) or IFN gamma (200 U) in the presence or absence of tumor necrosis factor cu (TNF alpha, 10 ng/ml) over time (short term, 0-60 min; long term, 0, 24, 48 h). Fractionated or total cell lysates were evaluated by the Western blotting technique to determine the changes in the levels of signal transducers and activators of transcription (STAT), interferon regulatory factor 1 (IRF-1), and I kappa B alpha (I kappaB-alpha). Utilizing antibodies that recognize the nonphosphorylated forms of STAT-1 and STAT-3, it was determined that levels of STAT-1 and STAT-3 in total cell lysates were constitutively expressed and did not change in response to treatment with IFN gamma or TNFa. In contrast, nuclear levels of STAT-1 and phosphorylated STAT-3 were elevated in a time-dependent manner in response to IFN gamma treatment. Furthermore, IFN gamma and TNF alpha treatment elevated levels of IRF-1 within 2 h. TNF alpha -induced increases in the levels of IRF-1 were transient, whereas the levels of IRF-1 in response to IFN gamma treatment remained elevated at 48 h. These data suggest that IFN gamma treatment can activate members of the STAT pathway, resulting in increased levels of IRF-1. TNF alpha treatment induced a rapid decrease in the levels of I kappaB-alpha. IFN gamma treatment did not alter the levels of 1 kappaB-alpha and failed to inhibit the TNF alpha -initiated decrease in the levels of I kappaB-alpha, The present experiment demonstrates that the steroidogenic cells of the corpus luteum have the capacity to respond to IFN gamma via activation of STAT and IRF-1, providing further evidence that IFN gamma may be involved in the luteolytic process, These data also suggest that IFN gamma does not signal through the nuclear factor kappa B cell survival signaling pathway. C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Womens Res Inst, Wichita, KS 67214 USA. Univ Kansas, Sch Med, Dept Obstet & Gynecol, Wichita, KS 67214 USA. Vet Affairs Med Ctr, Wichita, KS 67218 USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, VBK137E-BYN,55 Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [R01-HD35934] NR 39 TC 10 Z9 10 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 2001 VL 64 IS 5 BP 1481 EP 1486 DI 10.1095/biolreprod64.5.1481 PG 6 WC Reproductive Biology SC Reproductive Biology GA 426TQ UT WOS:000168364800025 PM 11319155 ER PT J AU Tajima, F Deguchi, T Laver, JH Zeng, HQ Ogawa, M AF Tajima, F Deguchi, T Laver, JH Zeng, HQ Ogawa, M TI Reciprocal expression of CD38 and CD34 by adult murine hematopoietic stem cells SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR AB The effects of activation of adult murine stem cells on their expression of CD38 were studied using a murine transplantation model. First, the published finding that the majority of long-term engrafting cells from normal adult steady-state marrow are CD38(+) was confirmed. Next, it was determined that the majority of stem cells activated in vivo by injection of 5-fluorouracil (5-FU) or mobilized by granulocyte colony-stimulating factor are CD38(-). Stem cells that were activated in culture with interleukin-II and steel factor were also CD38-. Previous studies have shown that expression of CD34 by adult stem cells is also modulated by in vivo or in vitro activation. To determine whether there is reciprocal expression of CD38 and CD34, 4 populations of post-5-FU marrow cells were analyzed. The majority of the stem cells were in the CD38(-)CD34(+) fraction. However, secondary transplantation experiments indicated that when the bone marrow reaches steady state, the majority of the stem cells become CD38(+)CD34(-). In addition, the minority populations of CD34(+) stem cells that occur in steady-state bone marrow are CD38-. This reversible and reciprocal expression of CD38 and CD34 by murine stem cells may have implications for the phenotypes of human stem cells. (Blood, 2001;97:2618-2624) (C) 2001 by The American Society of Hematology. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 18 TC 52 Z9 54 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 MAY 1 PY 2001 VL 97 IS 9 BP 2618 EP 2624 DI 10.1182/blood.V97.9.2618 PG 7 WC Hematology SC Hematology GA 429KP UT WOS:000168516200016 PM 11313250 ER PT J AU Schmaltz, C Alpdogan, O Horndasch, KJ Muriglan, SJ Kappel, BJ Teshima, T Ferrara, JLM Burakoff, SJ van den Brink, MRM AF Schmaltz, C Alpdogan, O Horndasch, KJ Muriglan, SJ Kappel, BJ Teshima, T Ferrara, JLM Burakoff, SJ van den Brink, MRM TI Differential use of Fas ligand and perforin cytotoxic pathways by donor T cells in graft-versus-host disease and graft-versus-leukemia effect SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; MEDIATED CYTOTOXICITY; CYTOLYTIC ACTIVITY; DEPENDENT PATHWAY; DOWN-REGULATION; DEFICIENT MICE; APOPTOSIS; MECHANISMS; DEATH AB In allogeneic bone marrow transplantation (BMT) donor T cells are primarily responsible for antihost activity, resulting in graft-versus-host disease (GVHD), and for antileukemia activity, resulting in the graft-versus-leukemia (GVL) effect. The relative contributions of the Fas ligand (Fast) and perforin cytotoxic pathways in GVHD and GVL activity were studied by using FasL-defective or perforin-deficient donor T cells in murine parent --> F1 models for allogeneic bone marrow transplantation. It was found that FasL-defective B6.gld donor T cells display diminished GVHD activity but have intact GVL activity. In contrast, perforin-deficient B6.pfp(-/-) donor T cells have intact GVHD activity but display diminished GVL activity. Splenic T cells from recipients of B6,gld or B6.pfp(-/-) T cells had identical proliferative and cytokine responses to host antigens; however, splenic T cells from recipients of B6.pfp-/- T cells had no cytolytic activity against leukemia cells in a cytotoxicity assay, In experiments with selected CD4(+) or CD8(+) donor T cells, the FasL pathway was important for GVHD activity by both CD4(+) and CD8+ T cells, whereas the perforin pathway was required for CD8-mediated GVL activity. These data demonstrate in a murine model for allogeneic bone marrow transplantation that donor T cells mediate GVHD activity primarily through the FasL effector pathway and GVL activity through the perforin pathway. This suggests that donor T cells make differential use of cytolytic pathways and that the specific blockade of one cytotoxic pathway may be used to prevent GVHD without interfering with GVL activity. (Blood. 2001;97: 2886-2895) (C) 2001 by The American Society of Hematology. C1 Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. RP van den Brink, MRM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Lettering 1118,Mailbox 111,1275 York Ave, New York, NY 10021 USA. RI teshima, takanori/G-1671-2012 FU NCI NIH HHS [5PO1 CA39542] NR 56 TC 139 Z9 143 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 MAY 1 PY 2001 VL 97 IS 9 BP 2886 EP 2895 DI 10.1182/blood.V97.9.2886 PG 10 WC Hematology SC Hematology GA 429KP UT WOS:000168516200051 PM 11313285 ER PT J AU Kawada, H Ogawa, M AF Kawada, H Ogawa, M TI Hematopoietic progenitors and stem cells in murine muscle SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE hematopoietic progenitors and stem cells; mouse; skeletal muscle; cell culture; cell transplantation ID MARROW STROMAL CELLS; BONE-MARROW; IN-VIVO; NONHEMATOPOIETIC TISSUES; SKELETAL-MUSCLE; BRAIN; MICE; HEPATOCYTES; EXPRESSION; BLOOD AB We investigated hematopoietic capabilities of murine skeletal muscle using methylcellulose culture and transplantation into lethally irradiated mice. Muscle mononuclear cells (MNC) contained colony-forming cells and long-term engrafting cells. Studies using chimeric mice indicated a bone marrow origin of the hematopoietic cells in the muscle. We then separated muscle MNC by FACS sorting into Ly-5-positive cells and Ly-5-negative cells and analyzed their hematopoietic capability in vitro and in vivo. The hematopoietic progenitors and stem cells were present only in the Ly-5-positive fraction. (C) 2001 Academic Press. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 18 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAY-JUN PY 2001 VL 27 IS 3 BP 605 EP 609 DI 10.1006/bcmd.2001.0426 PG 5 WC Hematology SC Hematology GA 461QK UT WOS:000170374800006 PM 11482874 ER PT J AU Bianco, P Kuznetuov, SA Riminucci, M Ziran, N Calvi, L Kronenberg, HM Robey, PG Schipani, E AF Bianco, P Kuznetuov, SA Riminucci, M Ziran, N Calvi, L Kronenberg, HM Robey, PG Schipani, E TI Signaling via the PTH/PTHrP receptor negatively regulates the formation of hematopoietic marrow SO BONE LA English DT Meeting Abstract C1 Univ La Sapienza, Rome, Italy. NIH, NIDCR, CSDB, Bethesda, MD USA. Univ Aquila, I-67100 Laquila, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2001 VL 28 IS 5 SU S BP S83 EP S83 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 434PL UT WOS:000168825000074 ER PT J AU Kraemer, DF Nelson, HD Bauer, DC Helfand, M AF Kraemer, DF Nelson, HD Bauer, DC Helfand, M TI Economic comparison of diagnostic approaches for evaluating osteoporosis in older women SO BONE LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2001 VL 28 IS 5 SU S BP S241 EP S242 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 434PL UT WOS:000168825000770 ER PT J AU Kuizon, BD Salusky, IB Shoback, D Cambay, E Jueppner, H Goodman, WG AF Kuizon, BD Salusky, IB Shoback, D Cambay, E Jueppner, H Goodman, WG TI Increased calcium-sensing receptor expression in calcium-supplemented rats with renal failure SO BONE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Med Ctr, Endocrine Res Unit, San Francisco, CA USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2001 VL 28 IS 5 SU S BP S134 EP S134 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 434PL UT WOS:000168825000290 ER PT J AU Peters, JH Carsons, S Kalunian, K Yoshida, M Ko, F McDougall, S Hahn, TJ AF Peters, JH Carsons, S Kalunian, K Yoshida, M Ko, F McDougall, S Hahn, TJ TI The alternatively spliced EIIIA segment is preferentially exposed to antibody recognition in an osteoarthritic synovial fluid fibronectin fragment species SO BONE LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, GRECC, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Sacramento VA Med Ctr, Mather, CA USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2001 VL 28 IS 5 SU S BP S108 EP S108 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 434PL UT WOS:000168825000176 ER PT J AU Spitzer, TR AF Spitzer, TR TI Engraftment syndrome following hematopoietic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Review DE engraftment syndrome; stem cell transplantation ID BONE-MARROW TRANSPLANTATION; DIFFUSE ALVEOLAR HEMORRHAGE; VERSUS-HOST DISEASE; CAPILLARY LEAKAGE SYNDROME; HIGH-DOSE CHEMOTHERAPY; NECROSIS-FACTOR-ALPHA; THERAPY; RECIPIENTS; SUPPORT; MANIFESTATIONS AB During neutrophil recovery following hematopoietic stem cell transplantation, a constellation of symptoms and signs including fever, erythrodermatous skin rash, and noncardiogenic pulmonary edema often occur, These clinical findings have usually been referred to as engraftment syndrome, or, reflecting the manifestations of increased capillary permeability, capillary leak syndrome. While described most often following autologous stem cell transplantation, a similar clinical syndrome has been observed followed allogeneic stem cell transplantation. Distinction from graft-versus-host disease in the allogeneic setting however, has been difficult. Recent experience with non-myeloablative conditioning for stem cell transplantation, however, reveals that an engraftment syndrome independent of GVHD may occur. In some cases, this engraftment syndrome may be a manifestation of a host-versus-graft reaction (graft rejection). While cellular and cytokine interactions are believed to be responsible for these clinical findings, a distinct effector cell population and cytokine profile have not been defined, Engraftment syndromes are likely associated with an increased transplant-related mortality, mostly from pulmonary and associated multiorgan failure, Corticosteroid therapy is often dramatically effective for engraftment syndrome, particularly for the treatment of the pulmonary manifestations. A proposal for a more uniform definition of engraftment syndrome has been developed in order to allow for a reproducible method of reporting of this complication and for evaluating prophylactic and therapeutic strategies. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. NR 43 TC 175 Z9 186 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 2001 VL 27 IS 9 BP 893 EP 898 DI 10.1038/sj.bmt.1703015 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 440XK UT WOS:000169201800001 PM 11436099 ER PT J AU Schultze, JL Anderson, KC Gilleece, MH Gribben, JG Nadler, LM AF Schultze, JL Anderson, KC Gilleece, MH Gribben, JG Nadler, LM TI A pilot study of combined immunotherapy with autologous adoptive tumour-specific T-cell transfer, vaccination with CD40-activated malignant B cells and interleukin 2 SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE adoptive cell transfer; plasmacytic leukaemia; haematological malignancies; CD40 antigen; T cells ID BONE-MARROW; LYMPHOMA; LYMPHOCYTES; IMMUNITY AB Most B-cell malignancies are incurable diseases and therefore warrant new therapeutic approaches. In a pilot study, we tested the feasibility and safety of combined immunotherapy consisting of adoptive transfer of autologous tumour-specific T cells, low-dose interleukin 2 (IL-2) and a cellular vaccine of CD40-activated plasma cell leukaemia (PCL) cells in a patient who failed tandem repeat stem cell transplantation and idiotype vaccination. Autologous tumour-specific T cells for adoptive T-cell transfer were propagated in vitro by repetitive stimulation with autologous ex vivo CD40-activated PCL cells. CD40-activated PCL cells for vaccination were similarly generated ex vivo by co-culture with CD40 ligand transfectants. Autologous T cells (5 x 10(8) and 2.5 x 10(9) for two separate treatment cycles) generated ex vivo and cytotoxic against autologous tumours were infused and well tolerated by the patient. Fever and myalgias were closely related to IL-2 injections and no other adverse effects were observed. A temporary decrease of PCL cells in peripheral blood was seen after the first cycle of adoptive T-cell therapy, tumour cell vaccination and low-dose IL-2. Tumour progression was associated with tumour cells that (1) expressed a complex karyotype, (2) demonstrated loss of MHC class II, and (3) did not induce autologous tumour-specific T-cell lines ex vivo. We demonstrated the safety and feasibility in combining autologous tumour-specific T-cell therapy with low-dose IL-2 and that clinical trials based on the use of CD40-activated autologous tumour cell vaccines are warranted in patients with CD40-activated autologous tumour cells, either as a vaccine or for ex vivo stimulation of autologous T cells. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schultze, JL (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,D540C, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [CA66996, CA78378] NR 19 TC 24 Z9 25 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2001 VL 113 IS 2 BP 455 EP 460 DI 10.1046/j.1365-2141.2001.02760.x PG 6 WC Hematology SC Hematology GA 439AG UT WOS:000169086100030 PM 11380416 ER PT J AU Gritli, S Omar, S Tartaglini, E Guannouni, S Fleming, JC Steinkamp, MP Berul, CI Hafsia, R Baltagi-Ben Jilani, S Belhani, A Hamdi, M Neufeld, EJ AF Gritli, S Omar, S Tartaglini, E Guannouni, S Fleming, JC Steinkamp, MP Berul, CI Hafsia, R Baltagi-Ben Jilani, S Belhani, A Hamdi, M Neufeld, EJ TI A novel mutation in the SLC19A2 gene in a Tunisian family with thiamine-responsive megaloblastic anaemia, diabetes and deafness syndrome SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myelodysplasia; diabetes; deafness; cardiomyopathy; thiamine transporter ID ANEMIA SYNDROME; SENSORINEURAL DEAFNESS; MELLITUS; TRANSPORTER; LOCALIZATION; DEFICIENCY; DISORDER AB Thiamine-responsive megaloblastic anaemia (TRMA) syndrome with. diabetes and deafness was found in two patients from a Tunisian kindred. The proband was homozygous for a novel mutation, 287delG, in the high-affinity thiamine transporter gene, SLC19A2. We demonstrated that fibroblasts from this patient exhibited defective thiamine transport. These data confirm that the SLC19A2 gene is the high-affinity thiamine carrier and that this novel mutation is responsible for TRMA syndrome. C1 Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Hop Charles Nicolle, Div Genet & Immunol, Dept Pathol, Tunis, Tunisia. Hop Mongi Slim, Serv Cardiol, La Marsa, Tunisia. Hop Aziza Othmana, Hematol Lab, Tunis, Tunisia. Univ Ancona, Ist Biochim, Ancona, Italy. Hop Mil, Serv Pediat, Tunis, Tunisia. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Div Hematol & Oncol, Enders 720,300 Longwood Ave, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011; OI Steinkamp, Mara/0000-0003-1226-9325 FU NHLBI NIH HHS [HL04184, T32 HL07574] NR 35 TC 18 Z9 19 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 2001 VL 113 IS 2 BP 508 EP 513 DI 10.1046/j.1365-2141.2001.02774.x PG 6 WC Hematology SC Hematology GA 439AG UT WOS:000169086100038 PM 11380424 ER PT J AU Tavakkolizadeh, A Stephen, AE Kaihara, S Mooney, DL Kim, BS Ashley, SW Vacanti, JP Whang, EE AF Tavakkolizadeh, A Stephen, AE Kaihara, S Mooney, DL Kim, BS Ashley, SW Vacanti, JP Whang, EE TI Tissue-engineered intestine: assessment of morphology and enterocyte dynamics SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract C1 W Suffolk Hosp, Bury St Edmunds, Suffolk, England. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD MAY PY 2001 VL 88 SU 1 BP 15 EP 15 PG 1 WC Surgery SC Surgery GA 430YL UT WOS:000168603000049 ER PT J AU Ades, T Gansler, T Miller, M Rosenthal, DS AF Ades, T Gansler, T Miller, M Rosenthal, DS TI PC-SPES: Current evidence and remaining questions SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID PROSTATE-CANCER; SUPPLEMENT; EFFICACY C1 Amer Canc Soc, Atlanta, GA 30329 USA. Harvard Univ, Harvard Univ Hlth Serv, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Zakim Ctr Integrated Therapies, Cambridge, MA USA. RP Ades, T (reprint author), Amer Canc Soc, Atlanta, GA 30329 USA. NR 9 TC 5 Z9 5 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAY-JUN PY 2001 VL 51 IS 3 BP 199 EP 204 PG 6 WC Oncology SC Oncology GA 434YZ UT WOS:000168844600008 PM 11577497 ER PT J AU Kiel, DP Kauppila, LI Cupples, LA Hannan, MT O'Donnell, CJ Wilson, PWF AF Kiel, DP Kauppila, LI Cupples, LA Hannan, MT O'Donnell, CJ Wilson, PWF TI Bone loss and the progression of abdominal aortic calcification over a 25 year period: The Framingham Heart Study SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE osteoporosis; pathologic calcification; vascular disease; cohort study; aged ID POSTMENOPAUSAL WOMEN; ATHEROSCLEROTIC PLAQUES; ARTERIAL CALCIFICATION; MINERAL DENSITY; DEFICIENT MICE; MESSENGER-RNA; OSTEOPOROSIS; EXPRESSION; OSTEOPONTIN; PROTEIN AB Vascular calcification and osteoporosis are common age-related processes that are prominently displayed on routine lateral lumbar spine radiographs as dense calcium mineral deposits of the aorta that lie adjacent to osteopenic vertebrae. Using a population-based cohort of older men and women, we tested the hypothesis that the progression of vascular calcification of the abdominal aorta should be greatest in those individuals with the greatest amount of bone loss. From the original population-based Framingham Heart Study cohort, 364 women and 190 men had lateral lumbar spine and hand radiographs performed between 1966 and 1970 and repeated between 1992 and 1993. The lateral lumbar films were read for the presence of aortic calcification using a semiquantitative method, and the hand films were read for second metacarpal relative cortical area (MCA). Using multivariate regression techniques, the 25-year progression of the abdominal aortic calcification index was examined in relation to the change in the MCA, while adjusting for recognized risk factors for atherosclerotic cardiovascular disease. During the 25 years of followup, the MCA decreased by 22.4% in women (from 79.6 +/- 7.8 (SD) to 61.8 +/- 10.3) and by 13.3% in men (from 80.6 +/- 6.9 to 69.9 +/- 8.3), The aortic calcification score increased over eightfold in women (from 1.2 +/- 2.7 (SD) to 9.9 +/- 6.7) and sixfold in men (from 1.6 +/- 2.8 to 9.6 +/- 6.3). There was a significant association between percent change in MCA and change in aortic calcification index (P = 0.01) in women after controlling for all potential confounders. No association was observed in men (P = 0.50), including the 50% of men with the greatest bone loss. This is the first longitudinal study to show that women with the greatest magnitude of bone loss also demonstrate the most severe progression of abdominal aortic calcification, suggesting that the two processes may be related. C1 Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Kiel, DP (reprint author), Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. OI Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-38038]; NIAMS NIH HHS [R01 AR/AG 41398] NR 37 TC 274 Z9 288 U1 0 U2 8 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD MAY PY 2001 VL 68 IS 5 BP 271 EP 276 DI 10.1007/BF02390833 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 439CN UT WOS:000169093400002 PM 11683533 ER PT J AU Laham, R AF Laham, R TI Angiogenesis (clinical trials) SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 4th Meeting of the Canadian-Vascular-Biology-Working-Group CY AUG, 2000 CL CHARLEVOIX, CANADA SP Canadian Vasc Biol Working Grp DE angiogenesis; clinical trials; collateral circulation; coronary disease; growth substances; ischemia ID FIBROBLAST-GROWTH-FACTOR; CHRONIC MYOCARDIAL-ISCHEMIA; INCOMPLETE REVASCULARIZATION; BYPASS SURGERY; GENE-THERAPY; IN-VITRO; DELIVERY; DISEASE; MODEL; PIGS AB Therapeutic angiogenesis may play a role in the treatment of patients with vascular disease who have no other treatment option (those who are not candidates for bypass surgery or angioplasty). The first published clinical trial results appeared in 1998 and additional trials have since been completed or are ongoing. Results of several of these trials are reviewed. Studies of angiogenesis with basic fibroblast growth factor and human vascular endothelial growth factor suggest that these growth factors can induce functionally significant angiogenesis. Evolving delivery modalities and strategies are also highlighted. C1 Harvard Univ, Sch Med, Angiogenesis Res Ctr, BIDMC, Boston, MA 02215 USA. RP Laham, R (reprint author), Harvard Univ, Sch Med, Angiogenesis Res Ctr, BIDMC, 330 Brookline Ave, Boston, MA 02215 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD MAY PY 2001 VL 17 SU A BP 29A EP 32A PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 437NR UT WOS:000168998200008 PM 11381293 ER PT J AU Cady, B Michaelson, JS AF Cady, B Michaelson, JS TI The life-sparing potential of mammographic screening SO CANCER LA English DT Editorial Material ID CARCINOMA IN-SITU; TERM FOLLOW-UP; BREAST-CANCER; NATURAL-HISTORY; RECURRENCE; DIAGNOSIS; INTERVAL; BIOPSY; TRIAL; WOMEN C1 Brown Univ, Women & Infants Hosp, Breast Hlth Ctr, Providence, RI 02905 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cady, B (reprint author), Brown Univ, Women & Infants Hosp, Breast Hlth Ctr, 101 Dudley St, Providence, RI 02905 USA. NR 30 TC 43 Z9 43 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 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 2001 VL 91 IS 9 BP 1699 EP 1703 DI 10.1002/1097-0142(20010501)91:9<1699::AID-CNCR1186>3.0.CO;2-W PG 5 WC Oncology SC Oncology GA 425NT UT WOS:000168297900001 PM 11335893 ER PT J AU Michaud, DS Giovannucci, E Willett, WC Colditz, GA Fuchs, CS AF Michaud, DS Giovannucci, E Willett, WC Colditz, GA Fuchs, CS TI Coffee and alcohol consumption and the risk of pancreatic cancer in two prospective United States cohorts SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DIABETES-MELLITUS; TEA CONSUMPTION; QUESTIONNAIRE; CAFFEINE; EPIDEMIOLOGY; SMOKING; HISTORY; MEN AB Although most prospective cohort studies do not support an association between coffee consumption and pancreatic cancer, the findings for alcohol are inconsistent. Recently, a large prospective cohort study of women reported statistically significant elevations in risk of pancreatic cancer for both coffee and alcoholic beverage consumption. We obtained data on coffee, alcohol, and other dietary factors using semiquantitative food frequency questionnaires administered at baseline (1986 in the Health Professionals Follow-Up Study and 1980 in the Nurses' Health Study) and in subsequent follow-up questionnaires. Data on other risk factors for pancreatic cancer, including cigarette smoking, were also available. Individuals with a history of cancer at study initiation were excluded from all of the analyses. During the 1,907,222 person years of follow-up, 288 incident cases of pancreatic cancer were diagnosed. The data were analyzed separately for each cohort, and results were pooled to compute overall relative risks (RR), Neither coffee nor alcohol intakes were associated with an increased risk of pancreatic cancer in either cohort or after pooling the results (pooled RR, 0.62; 95% confidence interval, 0.27-1.43, for >3 cups of coffee/day versus none; and pooled RR, 1.00; 95% confidence interval, 0.57-1.76, for greater than or equal to 30 grams of alcohol/day versus none). The associations did not change with analyses examining different latency periods for coffee and alcohol. Similarly, no statistically significant associations were observed for intakes of tea, decaffeinated coffee, total caffeine, or alcoholic beverages. Data from these two large cohorts do not support any overall association between coffee intake or alcohol intake and risk of pancreatic cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Michaud, DS (reprint author), NCI, 6120 Execut Blvd,EPS Room 7026, Rockville, MD 20852 USA. RI Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 40356, CA 55075, CA 86102] NR 34 TC 80 Z9 84 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2001 VL 10 IS 5 BP 429 EP 437 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 433CM UT WOS:000168737800002 PM 11352851 ER PT J AU Zhou, W Thurston, SW Liu, G Xu, LL Miller, DP Wain, JC Lynch, TJ Su, L Christiani, DC AF Zhou, W Thurston, SW Liu, G Xu, LL Miller, DP Wain, JC Lynch, TJ Su, L Christiani, DC TI The interaction between microsomal epoxide hydrolase polymorphisms and cumulative cigarette smoking in different histological subtypes of lung cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; GENETIC-POLYMORPHISM; METABOLIZING-ENZYMES; RISK; SUSCEPTIBILITY; ASSOCIATION; EXPRESSION; CYP1A1; GENOTYPES; CARCINOMA AB Microsomal epoxide hydrolase (mEH) is involved in the metabolism of environmental and tobacco carcinogens. Smaller studies found inconsistent results in the relationship between mEH polymorphisms and lung cancer risk. We investigated the two polymorphisms of mEH in 974 Caucasian lung cancer patients and 1142 controls using PCR-RFLP techniques. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates, There was no overall relationship between mEH genotypes and lung cancer risk. The adjusted odds ratio (OR) of the very low activity genotype versus that of other genotypes combined was 1.00 [95% confidence interval (CT), 0.73-1.34]. However, gene-environment interaction analyses revealed that the ORs decreased as cumulative smoking (defined as square root of pack-years) increased. When pack-years = 0, the OR was 1.89 (95% CI, 1.08-3.28), When pack-years = 28.5, the OR was 1.00 (95% CI, 0.76-1.32), and when pack-years = 80, the OR decreased to 0.65 (95% CI, 0.42-1.00). When cases were stratified according to histological subtypes, the interaction between mEH genotype and cumulative smoking was statistically significant (P < 0.01) for the 222 squamous cell carcinoma cases, whereas it was not significant (P 0.18) for the 432 adenocarcinoma cases. In conclusion, cumulative cigarette smoking plays a pivotal role in the association between mEH polymorphisms and lung cancer risk, altering the direction of risk (in the case of the very low activity genotype) from a risk factor in nonsmokers to a relatively protective factor in heavy smokers. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Liu, Geoffrey/N-4421-2016 FU FIC NIH HHS [TW 00828]; NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES00002, ES/CA 06409] NR 35 TC 77 Z9 84 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2001 VL 10 IS 5 BP 461 EP 466 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 433CM UT WOS:000168737800006 PM 11352855 ER PT J AU Pauler, DK Menon, U McIntosh, M Symecko, HL Skates, SJ Jacobs, IJ AF Pauler, DK Menon, U McIntosh, M Symecko, HL Skates, SJ Jacobs, IJ TI Factors influencing serum CA125II levels in healthy postmenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CA 125 LEVELS; OVARIAN-CANCER; CA-125 LEVELS; GYNECOLOGIC PATIENTS; ANTIGEN; MODELS; ASSAY; RISK AB Our objective was to identify factors that correlate with CA125 concentrations in healthy postmenopausal women and to introduce recommendations for reporting and interpreting individual CA125 assay results. We analyzed repeated serum CA125 levels, as measured by the CA125II assay, in 18,748 postmenopausal women who participated in the St. Bartholomew's/Royal London Hospital Ovarian Cancer screening trial from 1986 to 1994 and were not diagnosed with ovarian cancer during the l2-year follow-up period. We found that race is a substantial predictor of normal levels of CA125, with average CA125II concentration from African (median, 9.0; 95% range, 4.0-26.0 units/ml) and Asian women (median, 13.0; range, 5.9-33.3 units/ml) lower than that in Caucasian women (median, 14.2; range, 6.0-41.0 units/ml; P < 0.001). Women with a hysterectomy have lower CA125II values (median, 13.6; range 5.5-39.0 units/ml; P < 0.001), and women with a prior cancer diagnosis other than ovarian cancer have higher levels of CA125 II (median, 16.0; range, 6.0-49.0 units/ml; P < 0.003), Regular smoking and caffeine consumption decrease CA125 levels (P < 0.001). A woman's age, age at menarche, age at menopause, and history of a previous ovarian cyst (P < 0.05) are also predictive of baseline CA125 levels. Parity, history of hormone replacement therapy or unilateral oopherectomy, and previous use of oral contraceptives or talcum powder are not significant predictors of CA125 concentrations (P > 0,05). We concluded that clinically significant differences in individual patient characteristics need to be reflected in the screening algorithms that use CA125II so that designed performance characteristics (sensitivity and specificity) are maintained in practice. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. St Bartholomews & Royal London Hosp, London, England. RP Pauler, DK (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,MP-557,POB 19024, Seattle, WA 98109 USA. RI Menon, Usha/C-4716-2008; Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 FU NCI NIH HHS [CA57693] NR 32 TC 65 Z9 69 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2001 VL 10 IS 5 BP 489 EP 493 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 433CM UT WOS:000168737800010 PM 11352859 ER PT J AU Alyea, EP Anderson, KC AF Alyea, EP Anderson, KC TI Allotransplantation for multiple myeloma SO CANCER JOURNAL LA English DT Article ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; CYTOTOXIC T-LYMPHOCYTES; GRAFT-VERSUS-MYELOMA; HIGH-DOSE THERAPY; ALLOGENEIC TRANSPLANTATION; DENDRITIC CELLS; MONOCLONAL GAMMOPATHIES; IDIOTYPE VACCINATION; ANTITUMOR IMMUNITY C1 Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Alyea, EP (reprint author), Dana Farber Canc Inst, Div Adult Oncol, 44 Binney St, Boston, MA 02215 USA. FU NCI NIH HHS [CA 78378] NR 55 TC 0 Z9 0 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAY-JUN PY 2001 VL 7 IS 3 BP 166 EP 174 PG 9 WC Oncology SC Oncology GA 444AG UT WOS:000169375300001 PM 11419023 ER PT J AU Cusack, JC Liu, R Houston, M Abendroth, K Elliott, PJ Adams, J Baldwin, AS AF Cusack, JC Liu, R Houston, M Abendroth, K Elliott, PJ Adams, J Baldwin, AS TI Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: Implications for systemic nuclear factor-kappa B inhibition SO CANCER RESEARCH LA English DT Article ID INDUCED APOPTOSIS; INDUCIBLE CHEMORESISTANCE; CANCER-THERAPY; CELLS; ACTIVATION; ALPHA; P53; PROTEOLYSIS; INDUCTION; INSIGHTS AB Inducible activation of nuclear factor-kappaB (NF-kappaB) inhibits the apoptotic response to chemotherapy and irradiation. Activation of NF-kappaB via phosphorylation of an inhibitor protein I kappaB leads to degradation of I kappaB through the ubiquitin-proteasome pathway. We hypothesized that inactivation of proteasome function will inhibit inducible NF-kappaB activation, thereby increasing levels of apoptosis in response to chemotherapy and enhancing antitumor effects, To assess the effects of proteasome inhibition on chemotherapy response, human colorectal cancer cells were pretreated with the dipeptide boronic acid analogue PS-341 (1 muM) prior to exposure to SN-38, the active metabolite of the topoisomerase I inhibitor, CPT-11, Inducible activation of NF-kappaB and growth response were evaluated in vitro and in vivo. Effects on p53, p21, p27 and apoptosis were determined. Pretreatment with PS-341 inhibited activation of NF-kappaB induced by SN-38 and resulted in a significantly higher level of growth inhibition (64-75%) compared with treatment with PS-341 alone (20-30%) or SN-38 alone (24-47%; P < 0.002). Combination therapy resulted in a 94% decrease in tumor size compared with the control group and significantly improved tumoricidal response to treatment compared with all treatment groups (P = 0.02). The level of apoptosis was 80-90% in the treatment group that received combination treatment compared with treatment with single agent alone (10%), Proteasome inhibition blocks chemotherapy-induced NF-B activation, leading to a dramatic augmentation of chemosensitivity and enhanced apoptosis, Combining proteasome inhibition with chemotherapy has significant potential to overcome the high incidence of chemotherapy resistance. Clinical studies are currently in development to evaluate the role of proteasome Inhibition as an important adjuvant to systemic chemotherapy. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. RP Cusack, JC (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Cox Bldg,Room 626,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA72771, CA73756, CA75080, CA75528, CA58223] NR 29 TC 469 Z9 492 U1 1 U2 14 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 MAY 1 PY 2001 VL 61 IS 9 BP 3535 EP 3540 PG 6 WC Oncology SC Oncology GA 428WV UT WOS:000168485400001 PM 11325813 ER PT J AU Chansky, HA Hu, M Hickstein, DD Yang, L AF Chansky, HA Hu, M Hickstein, DD Yang, L TI Oncogenic TLS/ERG and EWS/Fli-1 fusion proteins inhibit RNA splicing mediated by YB-1 protein SO CANCER RESEARCH LA English DT Article ID BINDING-PROTEIN; POLYMERASE-II; EWINGS-SARCOMA; GENE; TRANSCRIPTION; TRANSLOCATION; INTERACTS; LIPOSARCOMA; EXPRESSION; TLS/FUS AB The translocation liposarcoma protein TLS has recently been shown to function as an adapter molecule coupling gene transcription to RNA splicing. Here we demonstrate that YB-1, a protein known to play important roles in transcription and translation, interacts with the COOH-terminal domains of TLS and the structurally related Ewing's sarcoma protein EWS. Through this interaction, YB-1 is recruited to RNA polymerase II and promotes splicing of E1A pre-mRNA to the 13S isoform, This splicing function of YB-1 is inhibited by exogenous TLS/ERG or EWS/ Fli-1 fusion proteins, which bind to RNA polymerase II but fail to recruit the YB-1 protein. In Ewing's sarcoma cells that express endogenous EWS/Fli-1, this linkage between YB-1 and RNA pol II via EWS (or TLS) was found to be defective. Together, these results suggest that TLS and EWS fusion proteins may contribute to malignant transformation through disruption of RNA splicing mediated by TLS- and EWS-binding proteins such as YB-1. C1 Univ Washington, Sch Med, Dept Orthoped, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. NCI, Bethesda, MD 20892 USA. RP Yang, L (reprint author), Univ Washington, Sch Med, Dept Orthoped, GMR-151,1660 S Columbian Way, Seattle, WA 98108 USA. NR 20 TC 114 Z9 124 U1 1 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 MAY 1 PY 2001 VL 61 IS 9 BP 3586 EP 3590 PG 5 WC Oncology SC Oncology GA 428WV UT WOS:000168485400012 PM 11325824 ER PT J AU Albert, CM Ruskin, JN AF Albert, CM Ruskin, JN TI Risk stratifiers for sudden cardiac death (SCD) in the community: primary prevention of SCD SO CARDIOVASCULAR RESEARCH LA English DT Review DE epidemiology; sudden death; ventricular arrhythmias ID CORONARY HEART-DISEASE; POLYUNSATURATED FATTY-ACIDS; FACTOR INTERVENTION TRIAL; TIME PHYSICAL-ACTIVITY; MYOCARDIAL-INFARCTION; FISH CONSUMPTION; ARTERY DISEASE; RATE-VARIABILITY; LEISURE-TIME; VENTRICULAR DYSFUNCTION C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. RP Albert, CM (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. NR 84 TC 15 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAY PY 2001 VL 50 IS 2 BP 186 EP 196 DI 10.1016/S0008-6363(00)00319-9 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 432GU UT WOS:000168684500003 PM 11334822 ER PT J AU Zang, Y Beard, RL Chandraratna, RAS Kang, JX AF Zang, Y Beard, RL Chandraratna, RAS Kang, JX TI Evidence of a lysosomal pathway for apoptosis induced by the synthetic retinoid CD437 in human leukemia HL-60 cells SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE CD437; apoptosis; lysosomes; cathepsin D; free radicals ID LUNG-CARCINOMA CELLS; FACTOR-II RECEPTOR; CATHEPSIN-D; POSTTRANSCRIPTIONAL REGULATION; INTERFERON-GAMMA; GROWTH ARREST; IN-VITRO; INDUCTION; ACID; DEATH AB The novel synthetic retinoid 6-[3-(1-adamantyl)-4-hydroxy- phenyl]-2-naphtalene carboxylic acid (AHPN/CD437) has been proven to be a potent inducer of apoptosis in a variety of tumor cell types. However, the mechanism of its action remains to be elucidated, Recent studies suggest that the lysosomal protease cathepsin D, when released from lysosomes to the cytosol, can initiate apoptosis, In this study, we examined whether cathepsin D and free radicals are involved in the CD437-induced apoptosis. Exposure of human leukemia HL-60 cells to CD437 resulted in rapid induction of apoptosis as indicated by caspase activation, phosphatidylserine exposure, mitochondrial alterations and morphological changes. Addition of the antioxidants alpha -tocopherol acetate effectively inhibited the CD437-induced apoptosis. Measurement of the intracellular free radicals indicated a rise in oxidative stress in CD437-treated cells, which could be attenuated by alpha -tocopherol acetate, Interestingly, pretreatment of cells with the cathepsin D inhibitor pepstatin A blocked the CD437-induced free radical formation and apoptotic effects, suggesting the involvement of cathepsin D, However, Western blotting revealed no difference in cellular quantity of any forms of cathepsin D between control cells and CD437-treated cells, whereas immunofluorescence analysis of the intracellular distribution of cathepsin D showed release of the enzyme from lysosomes to the cytosol, Labeling of lysosomes with lysosomotropic probes confirmed that CD437 could induce lysosomal leakage. The CD437-induced relocation of cathepsin D could not be prevented by a-tocopherol acetate, suggesting that the lysosomal leakage precedes free radical formation. Furthermore, a retinoic acid nuclear receptor (RAR) antagonist failed to block these effects of CD437, suggesting that the action of CD437 is RAR-independent, Taken together, these data suggest a novel lysosomal pathway for CD437 induced apoptosis, in which lysosomes are the primary target and cathepsin D and free radicals act as death mediators. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Allergan Pharmaceut, Retinoid Res, Irvine, CA 92713 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Room 4433,149 13th St, Charlestown, MA USA. FU NCI NIH HHS [CA-79553] NR 32 TC 95 Z9 99 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAY PY 2001 VL 8 IS 5 BP 477 EP 485 DI 10.1038/sj.cdd.4400843 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 429UF UT WOS:000168534800005 PM 11423908 ER PT J AU Lindsey, M Wedin, K Brown, MD Keller, C Evans, AJ Smolen, J Burns, AR Rossen, RD Michael, L Entman, M AF Lindsey, M Wedin, K Brown, MD Keller, C Evans, AJ Smolen, J Burns, AR Rossen, RD Michael, L Entman, M TI Matrix-dependent mechanism of neutrophil-mediated release and activation of matrix metalloproteinase 9 in myocardial ischernia/reperfusion SO CIRCULATION LA English DT Article DE metalloproteinases; ischemia; reperfusion; blood cells ID ISCHEMIC MYOCARDIUM; INHIBITOR BLOCKS; EARLY REPERFUSION; ALPHA RECEPTORS; CARDIAC LYMPH; GROWTH-FACTOR; TNF RECEPTOR; CELL BIOLOGY; NECROSIS; INJURY AB Background-A key component of reperfusion of myocardial infarction is an immediate inflammatory response. which enhances tissue repair. Matrix turnover is crucial to tissue repair, and matrix metalloproteinases (MMPs) are key enzymes involved in matrix degradation. The hypothesis tested is that one inflammation-based effector of tissue repair is the secretion and activation of MMP-9 by infiltrating neutrophils, Methods and Results-Cardiac lymph and tissue were assayed for latent and active MMP-2 and MMP-9 by zymography and immunochemistry. Dual-labeling immunofluorescence determined the cellular source of MMP-9 protein. Isolated canine neutrophils were incubated with preischemic and postischemic cardiac lymph in the presence and absence of collagen-fibronectin pads, and the supernatants were assayed for latent and active MMP-9. MMP-9 increased during the first hours of reperfusion in both lymph supernatants and myocardial extracts, and this increase was of neutrophil origin. MMP-9 in the cardiac lymph remained latent but was activatable, In contrast, MMP-9 in the myocardium was in both latent and active forms. In situ zymography demonstrated that activated MMP-9 surrounded the infiltrated neutrophils. When postischemic cardiac lymph was incubated with neutrophils in vitro, MMP-9 secretion and activation occurred only in the presence of a collagen-fibronectin substrate; preischemic cardiac lymph did nor induce significant secretion or activation. Conclusions-Infiltrating neutrophils are an early source of MMP-9 after reperfusion, and a portion of MMP-9 in the myocardium is active. Infiltrating neutrophils may localize MMP-9 activation by secreting MMP-9 and as a source of activating proteases. C1 Houston VA Med Ctr, Res Ctr AIDS & HIV Infect, Houston, TX USA. Texas Childrens Hosp, Speros P Martel Lab Leukocyte Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Methodist Hosp, Cardiovasc Sci Sect, Dept Med, DeBakey Heart Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Immunol Res Lab, Houston, TX USA. RP Entman, M (reprint author), Baylor Coll Med, Dept Med, 1Baylor Plaza,MS F602, Houston, TX 77030 USA. RI Lindsey, Merry/B-2650-2012 FU NHLBI NIH HHS [1-T32-HL-07816-03, P01-HL-42550] NR 45 TC 147 Z9 160 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 2001 VL 103 IS 17 BP 2181 EP 2187 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 430PQ UT WOS:000168583700011 PM 11331260 ER PT J AU Yang, JM Lewandrowski, KB AF Yang, JM Lewandrowski, KB TI Urine drugs of abuse testing at the point-of-care: clinical interpretation and programmatic considerations with specific reference to the Syva Rapid Test (SRT) SO CLINICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 18th International Symposium on Critical Care Testing in the New Millennium: the Integration of Point-of-Care Testing CY JUN 01-04, 2000 CL HELSINGOR, DENMARK SP Abbott Labs, Bayer corp, HemoCue Inc, Instrumentat Lab Co, Radiometer Med, Roche Diag Corp, A&T Corp, ALV Med Instruments Nordic, Beckman Coulter Inc, Biokit Co Ltd, Bionostics, Daiichi Pure Chem Co Ltd, Denka Seiken Co Ltd, Fresenius Corp Germany, Int Reagents Corp, Iatron Labs Inc, Kanto Chem Co Inc, Medica Corp, Nova Biomed Corp, Olympus Opt Co Ltd, Ono Pharmaceut Co Ltd, Radiometer Trading KK, Wako Pure Chem Ind Ltd DE point-of-care; drugs of abuse screening AB We evaluated a new point-of-care (POC) device for urine drugs of abuse (DOA) screening including appropriate clinical interpretation and potential benefits in a large academic medical center. Two hundred consecutive urine samples were tested using Syva Rapid Test (SRT) and existing laboratory methods (Syva EMIT II). Agreement between methods was acceptable with some considerations. Threshold concentration differences, drug interferences, and cross-reactivity profiles of the class-specific assays resulted in performance differences between the POC and central laboratory methods. Clinical interpretation of POC results requires an understanding of these issues as well as the limitations of urine testing. While urine-based screening is used in workplace testing and in a variety of clinical applications, quantitative blood measurements of some drugs (e.g. ethanol, acetaminophen, salicylate, +/-tricyclic antidepressants) will remain important in the emergent setting. Performance of the SRT method takes approximately 10 min. Consequently, the major advantage over laboratory methods is rapid turnaround time. At the Massachusetts General Hospital, the most important application is for samples from the emergency department (about 1700/year). Each institution should assess its own needs and capabilities with regard to POC versus laboratory-based testing for DOA. (C) 2001 Published by Elsevier Science B.V. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 2 TC 7 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAY PY 2001 VL 307 IS 1-2 BP 27 EP 32 DI 10.1016/S0009-8981(01)00457-0 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 439CM UT WOS:000169093300006 PM 11369333 ER PT J AU Lewandrowski, E Mac Millan, D Misiano, D Tochka, L Lewandrowski, K AF Lewandrowski, E Mac Millan, D Misiano, D Tochka, L Lewandrowski, K TI Process improvement for bedside capillary glucose testing in a large academic medical center: the impact of new technology on point-of-care testing SO CLINICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 18th International Symposium on Critical Care Testing in the New Millennium: the Integration of Point-of-Care Testing CY JUN 01-04, 2000 CL HELSINGOR, DENMARK SP Abbott Labs, Bayer corp, HemoCue Inc, Instrumentat Lab Co, Radiometer Med, Roche Diag Corp, A&T Corp, ALV Med Instruments Nordic, Beckman Coulter Inc, Biokit Co Ltd, Bionostics, Daiichi Pure Chem Co Ltd, Denka Seiken Co Ltd, Fresenius Corp Germany, Int Reagents Corp, Iatron Labs Inc, Kanto Chem Co Inc, Medica Corp, Nova Biomed Corp, Olympus Opt Co Ltd, Ono Pharmaceut Co Ltd, Radiometer Trading KK, Wako Pure Chem Ind Ltd DE point-of-care; capillary glucose testing; bedside testing; process improvement ID BLOOD-GLUCOSE AB Point-of-care testing (POCT) for the management of patients with diabetes has become a standard of care. Originally, diabetic monitoring was accomplished by manual urine dipsticks. The development of hand-held, battery-operated capillary glucose monitors radically improved the ability of physicians and nurses to monitor diabetic patients during their hospital stay. Capillary glucose meters have been shown to provide accurate results under controlled conditions, but a number of early meters had issues with the quality of testing when used by non-laboratory personnel. Bedside capillary glucose testing was first initiated in our hospital in 1990, using a first-generation glucose meter that could measure a glucose value within 2 min. Operator errors were common because the glucose strips required wiping and the testing required timing. Furthermore, these early meters had no data storage or data management capabilities. In 1995, we transitioned to a second-generation meter with a rudimentary data management and storage capability that could be downloaded to a portable laptop. A log of quality control (QC) data could be derived from the download. A major problem with this device was the need to bring the instruments and laptop together, which was labor intensive and difficult to sustain over long periods of time in a large institution. We recently implemented a third-generation instrument (the Abbott Precision PCx) with a data management system (Precision NET). This device significantly expands the data management and networking capabilities of the bedside glucose meter, as shown in Table 5. Glucose Values can now be performed in a fraction of the time of the first-generation meters, the need to wipe the glucose strips has been eliminated, and only certified operators can use the instrument. Networking technology allows for centralized quality control management, and the ability to network with other point-of-care technologies using intranet and in the near future internet applications. Collectively, these developments have radically improved the efficiency and quality of bedside capillary glucose testing, and have significantly enhanced the ability to manage this important technology. (C) 2001 Published by Elsevier Science B.V. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Lewandrowski, K (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 5 Chem, Boston, MA 02114 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAY PY 2001 VL 307 IS 1-2 BP 175 EP 179 DI 10.1016/S0009-8981(01)00462-4 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 439CM UT WOS:000169093300027 PM 11369354 ER PT J AU McGibbon, CA Puniello, MS Krebs, DE AF McGibbon, CA Puniello, MS Krebs, DE TI Mechanical energy transfer during gait in relation to strength impairment and pathology in elderly women SO CLINICAL BIOMECHANICS LA English DT Article DE gait analysis; mechanical energy transfer; muscle strength; elderly; functional limitations ID MUSCLE STRENGTH; POWER; KINEMATICS; EXERCISE; BALANCE; FALLS; MEN; AGE AB Objective: To examine the relationships among strength impairment, pathology and the mechanical energy transfers across the leg and low-back joints in a sample of frail elderly women with functional limitations. Background: Past studies suggest mechanical energy analyses may be useful for identifying compensatory strategies used by elders during gait, but also suggest that age and strength are not the only factors that determine the extent of compensatory strategy use. Methods: Gait data for 75 functionally limited women 60-90 years of age were analyzed. Subjects were categorized by strength and pathology diagnoses. Inverse dynamics was used to compute concentric (positive) and eccentric (negative) mechanical energy expenditures of the ankle, knee, hip and low-back during the stance phase of gait. Joint mechanical energy expenditures were compared between strength and diagnoses groups, and relationships among joint mechanical energy expenditures examined within groups. Results: Weaker subjects demonstrated lower concentric ankle and eccentric knee mechanical energy expenditures, and higher eccentric low-back mechanical energy expenditures, than stronger subjects. Subjects with orthopaedic impairments demonstrated higher eccentric low-back mechanical energy expenditures than subjects with other impairments. Inverse correlations were found between ankle mechanical energy expenditures and hip and low-back mechanical energy expenditures for subjects with orthopaedic impairments. Conclusion: Elders with weak leg muscles and orthopaedic impairments increased hip and low-back mechanical energy expenditures, apparently to compensate for reduced ankle and knee mechanical energy expenditures. Further research is warranted to determine what long-term influences these compensatory strategies have on function and disability. C1 Massachusetts Gen Hosp, MGH Inst Hlth Profess, Biomot Lab, Dept Orthopaed,RSH 010, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, MGH Inst Hlth Profess, Biomot Lab, Dept Orthopaed,RSH 010, 40 Parkman St, Boston, MA 02114 USA. FU NIA NIH HHS [P50-AG11669, R01-AG12561] NR 23 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD MAY PY 2001 VL 16 IS 4 BP 324 EP 333 DI 10.1016/S0268-0033(01)00004-3 PG 10 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA 435RW UT WOS:000168895800008 PM 11358620 ER PT J AU Laposata, M AF Laposata, M TI Point-of-care coagulation testing: Stepping gently forward SO CLINICAL CHEMISTRY LA English DT Editorial Material ID PATIENT SELF-MANAGEMENT; ORAL ANTICOAGULATION; CONTROLLED TRIAL; WARFARIN C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Div Lab Med, Boston, MA 02114 USA. RP Laposata, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Div Lab Med, Gray Bldg,Rm 235, Boston, MA 02114 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 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 MAY PY 2001 VL 47 IS 5 BP 801 EP 802 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 427AT UT WOS:000168383200001 PM 11325878 ER PT J AU Wilson, ME Lorente, CA Allen, JE Eberhard, ML AF Wilson, ME Lorente, CA Allen, JE Eberhard, ML TI Gongylonema infection of the mouth in a resident of Cambridge, Massachusetts SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB We report a case of Gongylonema infection of the mouth, which caused a migrating, serpiginous tract in a resident of Massachusetts. This foodborne infection, which is acquired through accidental ingestion of an infected insect, such as a beetle or a roach, represents the 11th such case reported in the United States. C1 CDCP, Div Parasit Dis F13, Natl Ctr Infect Dis, PHS,US Dept HHS, Atlanta, GA 30341 USA. Harvard Univ, Sch Med, Boston, MA USA. Mt Auburn Hosp, Cambridge, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Harvard Vanguard Med Associates, Boston, MA USA. RP Eberhard, ML (reprint author), CDCP, Div Parasit Dis F13, Natl Ctr Infect Dis, PHS,US Dept HHS, 4770 Buford Hwy NE, Atlanta, GA 30341 USA. EM mle1@cdc.gov NR 7 TC 24 Z9 25 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2001 VL 32 IS 9 BP 1378 EP 1380 DI 10.1086/319991 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 429LF UT WOS:000168517900016 PM 11303277 ER PT J AU Hornicek, FJ Zych, GA Huston, JJ Malinin, TI AF Hornicek, FJ Zych, GA Huston, JJ Malinin, TI TI Salvage of humeral nonunions with onlay bone plate allograft augmentation SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FRACTURES AB Eight women and one man were treated for 10 established diaphyseal humeral nonunions, Six patients sustained fractures in motor vehicle accidents and two patients sustained fractures in a fall. Two of the fractures were open. One patient with multiple myeloma originally was treated conservatively and received local radiation, followed by open reduction and internal plate fixation, The other patients previously were treated with fracture braces, intramedullary nails, dynamic compression plates, or a combination of these techniques. After removal of the surgical hardware and fibrous tissue at the nonunion site, stable fixation was accomplished using a cortical long bone plate allograft (femoral and tibial) or fibular shaft allograft and a dynamic compression plate. All humeral nonunions had united at an average of 2.9 months. Radiographic incorporation of the allograft cortical hone plate and fibular shaft into the host cortex occurred in all but one patient by 3 months. Graft to host junction healing was accomplished by incorporation of the cortical allograft plate into the host cortex, resulting in an increased diameter of the bone. Cortical allograft bone plates and fibular grafts provide structural and probably osteoinductive support to enhance healing of these nonunions. C1 Univ Miami, Sch Med, Tissue Bank, Miami, FL USA. Univ Miami, Sch Med, Dept Orthopaed & Rehabil, Miami, FL USA. RP Hornicek, FJ (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol Unit, GRB 604A,55 Fruit St, Boston, MA 02114 USA. NR 15 TC 25 Z9 26 U1 0 U2 2 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 MAY PY 2001 IS 386 BP 203 EP 209 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 427ZY UT WOS:000168437700026 PM 11347837 ER PT J AU Kubaska, S Sahani, DV Saini, S Hahn, PF Halpern, E AF Kubaska, S Sahani, DV Saini, S Hahn, PF Halpern, E TI Dual contrast enhanced magnetic resonance imaging of the liver with superparamagnetic iron oxide followed by gadolinium for lesion detection and characterization SO CLINICAL RADIOLOGY LA English DT Article DE iron oxide; gadolinium; liver; MRI; signal intensity ID FOCAL HEPATIC-LESIONS; SPIN-ECHO; DIFFERENTIAL-DIAGNOSIS; MR; CT; METASTASES; TUMORS; FERUMOXIDES; EFFICACY; CHELATE AB AIM: Iron oxide contrast agents are useful for lesion detection, and extracellular gadolinium chelates are advocated for lesion characterization. We undertook a study to determine if dual contrast enhanced liver imaging with sequential use of ferumoxides particles and gadolinium (Gd)-DTPA can be performed in the same imaging protocol. MATERIALS AND METHODS: Sixteen patients underwent dual contrast magnetic resonance imaging (MRT) of the liver for evaluation of known/suspected focal lesions which included, metastases (n = 5), hepatocellular carcinoma (HCC; n = 3), cholangiocharcinoma (n = 1) and focal nodular hyperplasia (FNH; n = 3). Pre- and post-iron oxide T1-weighted gradient recalled echo (GRE) and T2-weighted fast spin echo (FSE) sequences were obtained, followed by post-Gd-DTPA (0.1 mmol/kg) multi-phase dynamic T1-weighted out-of-phase GRE imaging. Images were analysed in a blinded fashion by three experts using a three-point scoring system for lesion conspicuity on pre- and post-iron oxide T1 images as well as for reader's confidence in characterizing liver lesions on post Gd-DTPA T1 images. RESULTS: No statistically significant difference in lesion conspicuity was observed on pre- and post-iron oxide T1-GRE images in this small study cohort. The presence of iron oxide did not appreciably diminish image quality of post-gadolinium sequences and did not prevent characterization of liver lesions. CONCLUSION: Our results suggest that characterization of focal liver lesion with Gd-enhanced liver MRI is still possible following iron oxide enhanced imaging. Radiology, 56, 410-415 (C) 2001 The Royal College of Radiology. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Ellison 234-E,55 Fruit St, Boston, MA 02114 USA. NR 19 TC 33 Z9 37 U1 1 U2 7 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD MAY PY 2001 VL 56 IS 5 BP 410 EP 415 DI 10.1053/crad.2000.0673 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 437TY UT WOS:000169010700013 PM 11384141 ER PT J AU Vojta, C Kinosian, B Glick, H Altshuler, L Bauer, MS AF Vojta, C Kinosian, B Glick, H Altshuler, L Bauer, MS TI Self-reported quality of life across mood states in bipolar disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID DYSPHORIC MANIA; FOLLOW-UP; PSYCHOPATHOLOGY; HYPOMANIA; ILLNESS; LITHIUM AB In distinction to the classic conceptualization of mania and hypomania, a growing body of work indicates that these episodes are not typically characterized by euphoric mood and sense of increased well-being, but rather by significant dysphoric symptoms. However, few data exist concerning self-perceived quality of life in mania or hypomania. Such data are important both for better understanding of the illness, and are particularly important for developing appropriate cost-utility studies. Accordingly, we hypothesized that two measures of self-reported quality of life, the mental subscale of the Short Form-12 (SF-12) and the Euro-Qol, would show reduced quality of life in patients in manic/hypomanic or mixed episodes, compared to those who were euthymic. Eighty-six patients with bipolar disorder from four Department of Veterans Affairs (VA) medical centers were assessed in a cross-sectional design. Mood state was categorized by physician diagnosis and separately by patient self-report using the Internal State Scale (ISS). Self-reported quality of life was quantified using the SF-12 and EuroQol. Findings were identical regardless of how mood state was determined. The SF-12 mental subscale and EuroQol differed significantly across mood states. Patients with mania/hypomania were either less than (SF-12 mental subscale) or equal to (EuroQol) euthymic patients, while patients in a mixed episode resembled those in a depressive episode on both indices. In contrast, SF-12 physical subscale scores showed no intergroup differences. These quality-of-life data provide further support for the conceptualization that mania and hypomania are syndromes characterized by reduced, rather than increased, sense of well-being and quality of life. Moreover, depressive symptoms appear to be the primary determinant of quality of life in bipolar disorder, although other factors may be associated with both depression and reduced quality of life in bipolar disorder. Copyright (C) 2001 by W.B. Saunders Company. C1 VAMC, Providence, RI 02908 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Bauer, MS (reprint author), VAMC, 116R, Providence, RI 02908 USA. NR 25 TC 92 Z9 97 U1 1 U2 5 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 MAY-JUN PY 2001 VL 42 IS 3 BP 190 EP 195 DI 10.1053/comp.2001.23143 PG 6 WC Psychiatry SC Psychiatry GA 428NL UT WOS:000168467700002 PM 11349236 ER PT J AU Ichinose, F Erana-Garcia, J Hromi, J Raveh, Y Jones, R Krim, L Clark, MWH Winkler, JD Bloch, KD Zapol, WM AF Ichinose, F Erana-Garcia, J Hromi, J Raveh, Y Jones, R Krim, L Clark, MWH Winkler, JD Bloch, KD Zapol, WM TI Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension SO CRITICAL CARE MEDICINE LA English DT Article DE pulmonary hypertension; pulmonary vasodilator; nitric oxide; 3,5-cyclic guanosine monophosphate phosphodiesterase; phosphodiesterase inhibitor; sildenafil; aerosol drug therapy; respiratory therapy; inhalation drug administration; sheep ID INHALED NITRIC-OXIDE; RESPIRATORY-DISTRESS-SYNDROME; AWAKE LAMBS; ZAPRINAST; VASOCONSTRICTION; THERAPY AB Objective: To determine whether inhalation of aerosolized sildenafil with and without inhaled nitric oxide (NO) causes selective pulmonary vasodilation in a sheep model of pulmonary hypertension. Design: A controlled laboratory study in instrumented, awake, spontaneously breathing lambs. Setting: Animal research laboratory affiliated with a university hospital. Subject: Twenty Suffolk lambs. Interventions: Lambs were instrumented with a carotid artery catheter, a pulmonary artery catheter, and a tracheostomy tube and studied awake. After baseline measurements, pulmonary hypertension was induced by the continuous infusion of U46619, a thromboxane A(2) analog. After breathing three concentrations of inhaled NO (2, 5, and 20 ppm), lambs were divided into two groups. Group 1 (n = 7) breathed aerosols containing 1, 10, and 30 mg of sildenafil alone, and group 2 (n = 4) simultaneously breathed NO (2 and 5 ppm) and aerosols containing 10 mg of sildenafil. Hemodynamic measurements were obtained before and at the end of each drug administration. Venous admixture was calculated, and plasma cyclic guanosine monophosphate and sildenafil concentrations were measured. Measurements and Main Results: Aerosols containing 10 mg and 30 mg of sildenafil selectively decreased the pulmonary artery pressure by 21% +/- 3% and 26% +/- 3%, respectively (p < .05 vs. baseline pulmonary hypertension). When 10 mg of sildenafil was inhaled while simultaneously breathing 2 ppm and 5 ppm NO, the pulmonary artery pressure decreased by 35% +/- 3% and 43% +/- 2% (p < .05 vs. baseline pulmonary hypertension). Inhaled sildenafil did not impair systemic oxygenation, increase right-to-left intrapulmonary shunting, or impair the ability of inhaled NO to reduce right-to-left shunting. Conclusions: Nebulized sildenafil is a selective pulmonary vasodilator that can potentiate the pulmonary vasodilating effects of inhaled NO. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA USA. Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. Pfizer Cent Res, Sandwich, Kent, England. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL42397] NR 19 TC 114 Z9 118 U1 0 U2 0 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 MAY PY 2001 VL 29 IS 5 BP 1000 EP 1005 DI 10.1097/00003246-200105000-00024 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 431DB UT WOS:000168615700016 PM 11378612 ER PT J AU Robinson, DR AF Robinson, DR TI Clinical therapeutics SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Arthritis Unit, Boston, MA 02114 USA. RP Robinson, DR (reprint author), Massachusetts Gen Hosp, Arthritis Unit, Bullfinch 165,32 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAY PY 2001 VL 13 IS 3 BP 157 EP 158 DI 10.1097/00002281-200105000-00001 PG 2 WC Rheumatology SC Rheumatology GA 431CQ UT WOS:000168614700001 ER PT J AU Rahman, MU Poe, DS Choi, HK AF Rahman, MU Poe, DS Choi, HK TI Autoimmune vestibulo-cochlear disorders SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review ID INNER-EAR DISEASE; SENSORINEURAL HEARING-LOSS; T-CELL LINE; ENDOLYMPHATIC SAC; MENIERES-DISEASE; SYSTEMIC CIRCULATION; METHOTREXATE; ANTIBODIES; HEAT-SHOCK-PROTEIN-70; AUTOANTIBODIES AB Autoimmune vestibulo-cochlear disorders (AVCD) represent a group of syndromes with overlapping clinical features, manifesting as sensorineural hearing loss, often associated with vertigo, tinnitus, and aural fullness, and believed to be caused by an autoimmune mechanism. Although definitive evidence of a classic "autoimmune process" is still lacking, substantial indirect evidence has accumulated to strongly indicate such a pathogenesis. Rapidly progressing AVCD is analogous to rapidly progressive glomerulonephritis in that inner ear inflammation progresses to severe, irreversible damage within 3 months of onset (and often much more quickly). Thus patients with rapidly progressive AVCD are treated with a sense of urgency. Prompt treatment with corticosteroids and other antirheumatic/immunosuppressive agents can preserve hearing and vestibular functions. We are not aware of any randomized controlled clinical trials evaluating the efficacy of antirheumatic/immunosuppressive agents in AVCD. In this article we review reports of various therapies that have been tried in this condition and our experience of etanercept therapy in AVCD. (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Massachusetts Gen Hosp, Rheumatol Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rahman, MU (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Dept Med, Bullfinch 165,Fruit St, Boston, MA 02114 USA. NR 58 TC 27 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAY PY 2001 VL 13 IS 3 BP 184 EP 189 DI 10.1097/00002281-200105000-00006 PG 6 WC Rheumatology SC Rheumatology GA 431CQ UT WOS:000168614700006 PM 11333346 ER PT J AU Maldonado, I Reginato, AM Reginato, AJ AF Maldonado, I Reginato, AM Reginato, AJ TI Familial calcium crystal diseases: what have we learned? SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review ID FIBRODYSPLASIA OSSIFICANS PROGRESSIVA; POSTERIOR LONGITUDINAL LIGAMENT; DIHYDRATE DEPOSITION DISEASE; COFFIN-LOWRY-SYNDROME; SPONDYLOEPIPHYSEAL DYSPLASIA; PRECOCIOUS OSTEOARTHRITIS; ARTERIAL CALCIFICATION; ALKALINE-PHOSPHATASE; CHROMOSOME 5P; GENE COL2A1 AB The spectrum of heterotopic calcification or ossification is expanding because of the reports of several kindreds with calcium pyrophosphate deposition disease, apatite deposition disease, and others with less common syndromes associated with extracellular matrix calcification, such as fibrodysplasia ossificans progressiva and related syndromes. Genomic DNA studies in both humans and mice provide a shortcut to understanding the genetic basis of promotion and prevention of ECM calcification. Mutation in the COL2A1 gene has been identified in one family with spondyloepiphyseal dysplasia and calcium pyrophosphate and apatite crystalline deposits. In another kindred with precocious osteoarthritis without spondyloepiphyseal dysplasia, the phenotype was linked to markers of chromosome 8. In four other kindreds, the phenotypes were linked to an area of chromosome 5p. Two genes located in this region, which are expressed in articular cartilage, are being investigated as possible calcium pyrophosphate deposition disease genes. The results of linkage studies in three kindreds with articular/periarticular ADD with the COL2A1 gene were noninformative. Two different mouse mutations, the ank/ank and the ttw/ttw mice, are associated with intra-articular and ligament apatite deposits caused by a decrease in extracellular pyrophosphate concentrations, mimicking human arthritis caused by apatite deposition disease. Mutations in the matrix GLA protein, both in mice and in humans, are also associated with vascular and articular calcification. These mouse mutations provide cutting-edge information in the investigation of the mechanisms of apatite deposition in humans, (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Univ Oriente, Hosp Ruiz & Paez, Dept Med, Ciudad Bolivar, Venezuela. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Med Ctr, Robert Wood Johnson Med Sch, Cooper Hosp, Dept Med,Div Rheumatol, Camden, NJ USA. RP Reginato, AJ (reprint author), Div Rheumatol, Educ & Res Bldg,Suite 262,401 Haddon Ave, Camden, NJ 08103 USA. NR 74 TC 9 Z9 11 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAY PY 2001 VL 13 IS 3 BP 225 EP 233 DI 10.1097/00002281-200105000-00014 PG 9 WC Rheumatology SC Rheumatology GA 431CQ UT WOS:000168614700014 PM 11333354 ER PT J AU Schlesinger, N Schumacher, HR AF Schlesinger, N Schumacher, HR TI Goat: can management be improved? SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review ID URATE LOWERING DRUGS; INTRAVENOUS COLCHICINE; TRANSPLANT RECIPIENTS; GOUTY-ARTHRITIS; TRIAMCINOLONE ACETONIDE; INTERVAL GOUT; SERUM URATE; HYPERURICEMIA; LEVEL; AZATHIOPRINE AB Ongoing reviews of Cochrane collaboration show that there is still very little reliable information based on randomized controlled trials on which to base treatment decisions in acute and chronic gout, Recent studies have stressed that avoidance of factors contributing to development of gouty attacks such as diuretic therapy, weight gain, and alcohol consumption may lead to a decrease in gouty arthritis. Attention to minidose aspirin and its effect on serum uric acid levels was addressed. A low carbohydrate, high protein and unsaturated fat diet was recommended for gouty patients since they all enhance insulin sensitivity and therefore may promote a reduction in serum uric acid levels. Treatment of gout in transplant recipients brings into focus some of the issues regarding management of gout, because gout is a common problem among transplant patients. (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Rheumatol Sect, Dept Med, Newark, NJ 07103 USA. Univ Penn, Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Schlesinger, N (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Rheumatol Sect, Dept Med, 185 S Orange Ave,MSB 1-506, Newark, NJ 07103 USA. NR 41 TC 39 Z9 42 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAY PY 2001 VL 13 IS 3 BP 240 EP 244 DI 10.1097/00002281-200105000-00016 PG 5 WC Rheumatology SC Rheumatology GA 431CQ UT WOS:000168614700016 PM 11333356 ER PT J AU Levine, S Goldstein, AE Dahdouh, M Blank, P Hoffman, C Gropper, CA AF Levine, S Goldstein, AE Dahdouh, M Blank, P Hoffman, C Gropper, CA TI Cutaneous Acanthamoeba in a patient with AIDS: A case study with a review of new therapy SO CUTIS LA English DT Article ID OPPORTUNISTIC AMEBAS; INFECTION AB Cutaneous Acanthamoeba infection is a rare opportunistic infection in immunocompromised persons. We report a case of a patient with AIDS who developed disseminated Acanthamoeba secondary to chronic acanthamoebic sinusitis and review recent literature regarding new treatments for this relatively hard-to-treat disease. C1 St Barnabas Hosp, Dept Dermatol, Bronx, NY USA. St Barnabas Hosp, Dept Infect Dis, Bronx, NY USA. Mt Sinai Med Ctr, Dept Dermatol, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Levine, S (reprint author), 1717 86th St, Brooklyn, NY 11214 USA. NR 11 TC 9 Z9 9 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0011-4162 J9 CUTIS JI Cutis PD MAY PY 2001 VL 67 IS 5 BP 377 EP 380 PG 4 WC Dermatology SC Dermatology GA 458YC UT WOS:000170222200005 PM 11381852 ER PT J AU Dobens, LL Martin-Blanco, E Martinez-Arias, A Kafatos, FC Raftery, LA AF Dobens, LL Martin-Blanco, E Martinez-Arias, A Kafatos, FC Raftery, LA TI Drosophila puckered regulates Fos/Jun levels during follicle cell morphogenesis SO DEVELOPMENT LA English DT Article DE Drosophila oogenesis; epithelial migrations; JNK signaling; dual specificity phosphatase; small GTPase ID ACTIVATED PROTEIN-KINASES; AMINO-TERMINAL KINASE; DORSAL CLOSURE; RAS TRANSFORMATION; SIGNALING PATHWAY; DISTINCT ROLES; SMALL GTPASES; C-JUN; ACTIN CYTOSKELETON; SHEET MOVEMENT AB puckered (puc) encodes a VH1-like phosphatase that down-regulates Jun kinase (JNK) activity during dorsal closure of the Drosophila embryo. We report a role for puc in follicle cell morphogenesis during oogenesis, puc mRNA accumulates preferentially in the centripetally migrating follicle cells and cells of the elongating dorsal appendages. Proper levels of Puc activity in the follicle cells are critical for the production of a normal egg: either reduced or increased Puc activity result in incomplete nurse cell dumping and aberrant dorsal appendages. Phenotypes associated with puc mutant follicle cells include altered DE-cadherin expression in the follicle cells and a failure of nurse cell dumping to coordinate with dorsal appendage elongation, leading to the formation of cup-shaped egg chambers. The JNK pathway target A251-IacZ showed cell-type-specific differences in its regulation by puc and by the small GTPase DRacl. puc mutant cells displayed region-specific ectopic expression of the A251-lacZ enhancer trap whereas overexpression of a transgene encoding Puc was sufficient to suppress lacZ expression in a cell autonomous fashion. Strikingly, decreased or increased puc function leads to a corresponding increase or decrease, respectively, of Fos and Jun protein levels. Taken together, these data indicate that puc modulates gene expression responses by antagonizing a Rho GTPase signal transduction pathway that stabilizes the AP-1 transcription factor. Consistent with this, overexpression of a dominant negative DRacl resulted in lower levels of Fos/Jun. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England. European Mol Biol Lab, Heidelberg, Germany. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Dobens, LL (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI Martinez Arias, Alfonso/F-1966-2010; Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NIGMS NIH HHS [R01 GM060501] NR 57 TC 27 Z9 28 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 MAY PY 2001 VL 128 IS 10 BP 1845 EP 1856 PG 12 WC Developmental Biology SC Developmental Biology GA 438MJ UT WOS:000169057400012 PM 11311164 ER PT J AU Musi, N Fujii, N Hirshman, MF Ekberg, I Froberg, S Ljungqvist, O Thorell, A Goodyear, LJ AF Musi, N Fujii, N Hirshman, MF Ekberg, I Froberg, S Ljungqvist, O Thorell, A Goodyear, LJ TI AMP-activated protein kinase (AMPK) is activated in muscle of subjects with type 2 diabetes during exercise SO DIABETES LA English DT Article ID ACETYL-COA CARBOXYLASE; OBESE ZUCKER RAT; HUMAN SKELETAL-MUSCLE; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; RECEPTOR SUBSTRATE-1 PHOSPHORYLATION; GLUCOSE-TRANSPORTER TRANSLOCATION; INSULIN-RESISTANCE; GLUT4 TRANSLOCATION; MALONYL-COA; IN-VITRO AB Insulin-stimulated GLUT4 translocation is impaired in people with type 2 diabetes. In contrast, exercise results in a normal increase in GLUT4 translocation and glucose uptake in these patients. Several groups have recently hypothesized that exercise increases glucose uptake via an insulin-independent mechanism mediated by the activation of AMP-activated protein kinase (AMPK). If this hypothesis is correct, people with type 2 diabetes should have normal AMPK activation in response to exercise. Seven subjects with type 2 diabetes and eight matched control subjects exercised on a cycle ergometer for 45 min at 10% of maximum workload. Biopsies of vastus lateralis muscle were taken before exercise, after 20 and 45 min of exercise, and at 30 min postexercise. Blood glucose concentrations decreased from 7.6 to 4.77 mmol/l with 45 min of exercise in the diabetic group and did not change in the control group. Exercise significantly increased AMPK alpha2 activity 2.7-fold over basal at 20 min in both groups and remained elevated throughout the protocol, but there was no effect of exercise on AMPK alpha1 activity. Subjects with type 2 diabetes had similar protein expression of AMPK alpha1, alpha2, and beta1 in muscle compared with control subjects. AMPK alpha2 was shown to represent approximately two-thirds of the total alpha mRNA in the muscle from both groups. In conclusion, people with type 2 diabetes have normal exercise-induced AMPK alpha2 activity and normal expression of the alpha1, alpha2 and beta1 isoforms. Pharmacological activation of AMPK may be an attractive target for the treatment of type 2 diabetes. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Karolinska Inst, Ersta Hosp, Ctr Gastrointestinal Dis, Stockholm, Sweden. Huddinge Univ Hosp, Dept Surg, S-14186 Huddinge, Sweden. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR42338, AR45670] NR 57 TC 213 Z9 222 U1 1 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2001 VL 50 IS 5 BP 921 EP 927 DI 10.2337/diabetes.50.5.921 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 427EN UT WOS:000168392000002 PM 11334434 ER PT J AU Wrobel, JS Mayfield, JA Reiber, GE AF Wrobel, JS Mayfield, JA Reiber, GE TI Geographic variation of lower-extremity major amputation in individuals with and without diabetes in the Medicare population SO DIABETES CARE LA English DT Article ID HEALTH-CARE-DELIVERY; ARTERIAL RECONSTRUCTION; FOOT CARE; RATES AB OBJECTIVE - To describe geographic variation in rates of lower-limb major amputation in Medicare patients with and without diabetes. RESEARCH DESIGN AND METHODS - This cross-sectional population-based study used national fee-for-service Medicare claims from 1996 through 1997. The unit of analysis was 306 hospital referral regions (HRRs) representing health care markets for their respective tertiary medical centers Numerators were calculated rising nontraumatic major amputations and the diabetes code (250.x) for individuals with diabetes. Denominators for individuals with diabetes were created by multiplying the regional prevalence of diabetes (as determined using a 5% sample of Medicare Part B data identifying at least two visits with a diabetes code for 1995-1996) by the regional Medicare population. Denominators for individuals without diabetes were the remaining Medicare beneficiaries. Rates of major amputations were adjusted for age, sex, and race. RESULTS - Rates of major amputations per year were 3.83 per 1,000 (95% CI 3.60-4.06) individuals with diabetes compared with 0.38 per 1.000 (95% CI 0.35-0.41) individuals with out diabetes. Marked geographic variation was observed for individuals with and without diabetes: however, patterns were distinct between the two populations. Rates were high in the Southern and Atlantic states for individuals without diabetes. In contrast, rates for individuals with diabetes were widely varied. Variation across HRRs fur individuals with diabetes was 8.6-fold compared with 6.7-fold in individuals without diabetes for major amputations. CONCLUSIONS - Diabetes-related amputation rates exhibit high regional variation. even after age, sex, and race adjustment. Future work should be directed to exploring sources of this variation. C1 Vet Affairs Med & Reg Off Ctr, White River Junction, VT USA. Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH USA. Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Ctr Excellence Amputat Prosthet & Limb Loss Preve, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv & Epidemiol, Seattle, WA 98195 USA. RP Wrobel, JS (reprint author), VA White River Junct, Surg Serv 12, White River Junction, VT 05009 USA. NR 28 TC 99 Z9 103 U1 5 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2001 VL 24 IS 5 BP 860 EP 864 DI 10.2337/diacare.24.5.860 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 425VN UT WOS:000168312500013 PM 11347744 ER PT J AU Chalmers, K AF Chalmers, K TI The role of the certified diabetes educator in telephone counseling - Practical application SO DIABETES EDUCATOR LA English DT Article C1 Joslin Clin, Boston, MA 02215 USA. RP Chalmers, K (reprint author), Joslin Clin, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 2001 VL 27 IS 3 BP 379 EP 379 PG 1 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 438VE UT WOS:000169074300006 ER PT J AU Rosen, P Nawroth, PP King, G Moller, W Tritschler, HJ Packer, L AF Rosen, P Nawroth, PP King, G Moller, W Tritschler, HJ Packer, L TI The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Review DE oxidative stress; diabetes mellitus; vascular complications; neuropathy; insulin resistance ID PROTEIN-KINASE-C; ALPHA-LIPOIC ACID; LOW-DENSITY-LIPOPROTEIN; ENDOTHELIAL GROWTH-FACTOR; GLYCATION END-PRODUCTS; RANDOMIZED CONTROLLED TRIAL; IMPAIRED GLUCOSE-TOLERANCE; GLOMERULAR MESANGIAL CELLS; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B AB This review summarises the results and discussions of an UNESCO-MCBN supported symposium on oxidative stress and its role in the onset and progression of diabetes. There is convincing experimental and clinical evidence that the generation of reactive oxygen species (ROI) is increased in both types of diabetes and that the onset of diabetes is closely associated with oxidative stress. Nevertheless there is controversy about which markers of oxidative stress are most reliable and suitable for clinical practice. There are various mechanisms that contribute to the formation of ROI. It is generally accepted that vascular cells and especially the endothelium become one major source of ROI. An important role of oxidative stress for the development of vascular and neurological complications is suggested by experimental and clinical studies. The precise mechanisms by which oxidative stress may accelerate the development of complications in diabetes are only partly known. There is however evidence for a role of protein kinase C, advanced glycation end products (AGE) and activation of transcription factors such as NF kappaB, but the exact signalling pathways and the interactions with ROI remain a matter of discussion. Additionally, results of very recent studies suggest a role for ROI in the development of insulin resistance. ROI interfere with insulin signalling at various levels and are able to inhibit the translocation of GLUT4 in the plasma membrane. Evidence for a protective effect of antioxidants has been presented in experimental studies, but conclusive evidence from patient studies is missing. Large-scale clinical trials such as the DCCT Study or the UKPDS Study are needed to evaluate the long-term effects of antioxidants in diabetic patients and their potential to reduce the medical and socio-economic burden of diabetes and its complications. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Diabet Forschungsinst, D-40250 Dusseldorf, Germany. Univ Tubingen, Med Klin, D-7400 Tubingen, Germany. Joslin Diabet Ctr, Boston, MA 02215 USA. ASTA Med, Frankfurt, Germany. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Rosen, P (reprint author), Diabet Forschungsinst, Hennekamp 65, D-40250 Dusseldorf, Germany. NR 304 TC 523 Z9 546 U1 4 U2 28 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1520-7552 J9 DIABETES METAB RES JI Diabetes-Metab. Res. Rev. PD MAY-JUN PY 2001 VL 17 IS 3 BP 189 EP 212 DI 10.1002/dmrr.196 PG 24 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 444ZA UT WOS:000169431200004 PM 11424232 ER PT J AU Tatarkiewicz, K Garcia, M Omer, A Weir, GC De Vos, P AF Tatarkiewicz, K Garcia, M Omer, A Weir, GC De Vos, P TI C-peptide responses alter meal challenge in mice transplanted with microencapsulated rat islets SO DIABETOLOGIA LA English DT Article DE microencapsulation; transplantation; pancreatic islet; C peptide; meal challenge; diabetic mice ID PORCINE ISLETS; PANCREATIC-ISLETS; BIOARTIFICIAL PANCREAS; XENOGRAFT SURVIVAL; INSULIN-SECRETION; DIABETIC RATS; IN-VITRO; NOD MICE; REVERSAL; IMMUNOSUPPRESSION AB Aims/hypothesis. This study aimed to assess a response of microencapsulated rat islets to a meal challenge after being transplanted intraperitoneally into diabetic mice. Methods. Microencapsulated rat: islets or control naked syngeneic mouse islets were transplanted intraperitoneally into mice with streptozotocin-induced diabetes. Meal challenges were done 3, 6 and 9 weeks after transplantation. Glucose-induced insulin secretion from microencapsulated islets before and after transplantation was assessed in vitro. Results. Within the first week, all animals transplanted with either microencapsulated rat islets or with syngeneic murine islets became normoglycaemic ( < 11 mmol/l), At 4 and 6 weeks, body weight was less than normal in the non-diabetic control mice. Mice with the encapsulated rat islets had lower fasting glucose concentrations and more rapid glucose clearance after a meal challenge than the control mice, The group of mice with transplanted syngeneic islets had similar glucose profiles to control mice, except for slightly accelerated glucose clearance, The C peptide responses of mice with either microencapsulated or naked islets were clearly lower than the controls, An increase of C peptide appeared as early as 20 min in the plasma of the group with encapsulated islets, but this was considerably slower than in the other two groups, Microencapsulated rat islets retrieved 9 weeks after transplantation did not lose their ability to respond to glucose, but their output was less than half of the pretransplant control islets, Conclusions/interpretation. The delivery of C peptide and presumably the accompanying insulin are delayed by restrictions of the capsules and the peritoneal location, However, this delay in reaching peripheral target organs does not prevent microencapsulated grafts from efficiently clearing glucose after a meal. C1 Harvard Univ, Div Res, Sect Islet Transplantat & Cell Biol, Joslin Diabet Ctr,Med Sch, Boston, MA 02215 USA. Univ Groningen, Dept Surg, Groningen, Netherlands. RP Weir, GC (reprint author), Harvard Univ, Div Res, Sect Islet Transplantat & Cell Biol, Joslin Diabet Ctr,Med Sch, 1 Joslin Pl, Boston, MA 02215 USA. RI de Vos, Paul/A-3170-2013 FU NIDDK NIH HHS [DK 50657, DK-36836] NR 36 TC 24 Z9 25 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 2001 VL 44 IS 5 BP 646 EP 653 DI 10.1007/s001250051672 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 429PZ UT WOS:000168527300015 PM 11380084 ER PT J AU Hsu, SIH Yang, CML Sim, KG Hentschel, DM O'Leary, E Bonventre, JV AF Hsu, SIH Yang, CML Sim, KG Hentschel, DM O'Leary, E Bonventre, JV TI TRIP-Br: a novel family of PHD zinc finger- and bromodomain-interacting proteins that regulate the transcriptional activity of E2F-1/DP-1 SO EMBO JOURNAL LA English DT Article DE bromodomain; cell cycle; E2F-1; gene transcription; PHD zinc finger ID RETINOBLASTOMA GENE-PRODUCT; CELL-CYCLE PROGRESSION; NUCLEAR RECEPTORS; REPRESSOR DOMAIN; TRANSACTIVATION; IDENTIFICATION; EXPRESSION; BINDING; CLONING; RING AB We report the isolation of TRIP-Br1, a transcriptional regulator that interacts with the PHD-bromodomain of co-repressors of Kruppel-associated box (KRAB)-mediated repression, KRIP-1(TIF1 beta) and TIF1 alpha, as well as the co-activator/adaptor p300/CBP, TRIP-Br1 and the related protein TRIP-Br2 possess transactivation domains. Like MDM2, which has a homologous transactivation domain, TRIP-Br proteins functionally contact DP-1, stimulating E2F-1/DP-1 transcriptional activity. KRIP-1 potentiates TRIP-Br protein co-activation of E2F-1/DP-1, TRIP-Brl is a component of a multiprotein complex containing E2F-1 and DP-1. Co-expression of the retinoblastoma gene product (RB) abolishes baseline E2F-1/DP-1 transcriptional activity as well as TRIP-Br/KRIP-1 coactivation, both of which are restored by the adenovirus E1A once-protein. These features suggest that TRIP-Br proteins function at E2F-responsive promoters to integrate signals provided by PHD- and/or bromodomain-containing transcription factors. TRIP-Brl is identical to the cyclin-dependent kinase 4 (cdk4)-binding protein p34(SEI-1), which renders the activity of cyclin D/cdk4 resistant to the inhibitory effect of p16(INK4a) during late G(1). TRIP-Br1(p34(SEI-1)) is differentially overexpressed during the G1 and S phases of the cell cycle, consistent with a dual role for TRIP-Br1(p34(SEI-1)) in the regulation of cell cycle progression through sequential effects on the transcriptional activity of E2F-responsive promoters during G1 and S phases. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Natl Univ Singapore, Inst Mol & Cell Biol, Singapore 119260, Singapore. RP Bonventre, JV (reprint author), 149 13th St,Suite 4002, Charlestown, MA 02129 USA. RI ASTAR, IMCB/E-2320-2012 FU NIDDK NIH HHS [DK39773, R01 DK039773, R37 DK039773, T32 DK007540, T32 DK07540] NR 39 TC 72 Z9 78 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 2001 VL 20 IS 9 BP 2273 EP 2285 DI 10.1093/emboj/20.9.2273 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 430WC UT WOS:000168597600016 PM 11331592 ER PT J AU Meininger, G Grinspoon, S AF Meininger, G Grinspoon, S TI Regulation of the growth hormone/insulin-like growth factor-I axis in HIV disease SO ENDOCRINOLOGIST LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLACEBO-CONTROLLED TRIAL; MUSCLE PROTEIN-SYNTHESIS; IGF-BINDING PROTEINS; HORMONE SECRETION; ANOREXIA-NERVOSA; INFECTION; MEN; FAT; OBESITY AB The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis is significantly affected in human immunodeficiency virus (HIV) disease. Most often, physiologic regulation of the GH/IGF-I axis is linked closely to unique changes in nutritional status and body composition that are characteristic of HIV disease. Acquired growth hormone resistance, marked by increased growth hormone concentrations, occurs as a function of diminished weight and lean body mass in the acquired immunodeficiency syndrome (AIDS) wasting syndrome. Conversely, reduced growth hormone concentrations result from increased abdominal visceral adiposity in patients with the HIV lipodystrophy syndrome. Significant interest has focused on the use of growth hormone as a therapeutic strategy to increase muscle mass and weight in AIDS wasting and to reduce fat mass in HIV lipodystrophy. In this article, we review the physiologic regulation of the GH/IGF-I axis in HIV disease with a special emphasis on nutritional and body composition factors determining GH secretion and action in this population of patients. The use of growth hormone as an anabolic and lipolytic agent in HIV disease is also reviewed. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B, Boston, MA 02114 USA. NR 52 TC 2 Z9 2 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 MAY-JUN PY 2001 VL 11 IS 3 BP 188 EP 195 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 442RU UT WOS:000169299400005 ER PT J AU Klibanski, A Ho, K Freda, PU Clemmons, DR Barkan, AL Kleinberg, DL Trainer, PJ Swearingen, B Molitch, ME Wass, JAH Thorner, MO Melmed, S Strasburger, CJ Frohman, LA AF Klibanski, A Ho, K Freda, PU Clemmons, DR Barkan, AL Kleinberg, DL Trainer, PJ Swearingen, B Molitch, ME Wass, JAH Thorner, MO Melmed, S Strasburger, CJ Frohman, LA TI State-of-the-art strategies for the diagnosis and management of acromegaly SO ENDOCRINOLOGIST LA English DT Article ID SLOW-RELEASE LANREOTIDE; TRANSSPHENOIDAL SURGERY; FOLLOW-UP; THERAPY; OCTREOTIDE; DISEASE AB Elevation of blood levels of insulin-like growth factor I (IGF-I) is the most reliable diagnostic marker of growth hormone hypersecretion, and normalization of IGF-I levels is the principal criterion for documenting biochemical remission in patients with acromegaly. Levels of insulin like growth hormone-binding protein 3 also may be useful in the assessment of patients whose IGF-I levels are not definitively diagnostic of active disease. When surgical therapy for acromegaly is not curative, drugs such as the dopamine agonists and somatostatin analogues can be used to manage the disease; the somatostatin analogues are more effective than the dopamine agonists. In addition, a new class of agents for the medical management of acromegaly, the growth hormone receptor antagonists, may soon be available. The importance of biochemical control of acromegaly is suggested by a study of 149 acromegalic patients who had undergone transsphenoidal surgery; for those who were not cured, a 3.5-fold increase in the relative death risk was associated with each year of active disease compared with a year in biochemical remission. Moreover, primary drug therapy, rather than surgery, may be preferred in some circumstances; for example, when surgical cure is unlikely and no acute mass effects are present. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Garvan Inst Med Res, Dept Endocrinol, Sydney, NSW, Australia. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Univ N Carolina, Sch Med, Dept Med, Div Endocrinol & Metab, Chapel Hill, NC USA. Univ Michigan, Med Ctr, Div Endocrinol & Metab, Ann Arbor, MI USA. NYU Med Ctr, VA Med Ctr, Dept Med, New York, NY 10016 USA. Christie Hosp, Manchester, Lancs, England. Univ S Manchester Hosp, Manchester M20 8LR, Lancs, England. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Northwestern Univ, Sch Med, Ctr Endocrinol Metab Mol Med, Chicago, IL USA. Radcliffe Infirm, Dept Endocrinol, Oxford OX2 6HE, England. Univ Virginia, Hlth Sci Ctr, Dept Internal Med, Charlottesville, VA 22908 USA. Univ Calif Los Angeles, Sch Med, Cedars Sinai Res Inst, Dept Endocrinol Metab, Los Angeles, CA USA. Univ Munich, Innenstadt Hosp, Dept Med, Munich, Germany. Univ Illinois, Dept Med, Chicago, IL USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457,32 Fruit St, Boston, MA 02114 USA. RI Ho, Ken/E-5832-2011; OI Trainer, Peter/0000-0003-0146-3835 NR 28 TC 3 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD MAY-JUN PY 2001 VL 11 IS 3 BP 223 EP 232 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 442RU UT WOS:000169299400009 ER PT J AU Trivedi, N Hollister-Lock, J Lopez-Avalos, MD O'Neil, JJ Keegan, M Bonner-Weir, S Weir, GC AF Trivedi, N Hollister-Lock, J Lopez-Avalos, MD O'Neil, JJ Keegan, M Bonner-Weir, S Weir, GC TI Increase in beta-cell mass in transplanted porcine neonatal pancreatic cell clusters is due to proliferation of beta-cells and differentiation of duct cells SO ENDOCRINOLOGY LA English DT Article ID ISLET CELLS; NUDE-MICE; ENDOCRINE PANCREAS; RAT; GROWTH; REPLICATION; APOPTOSIS; ADULT; MODEL AB A 20-fold increase in beta -cell mass has been found after transplantation of porcine neonatal pancreatic cell clusters (NPCCs). Here the mechanisms leading to this increased beta -cell mass were studied. NPCCs (4000 islet equivalents) generated after 8 days culture of digested neonatal pig pancreas were transplanted beneath the renal capsule of streptozotocin (STZ) diabetic and normoglycemic nude mice. Grafts were removed at 10 days, 6 weeks, and 20 weeks after transplantation for immunostaining and insulin content. Proliferation of beta -cells and duct cells was assessed morphometrically using double immunostaining for Ki-67 with insulin or cytokeratin 7 (CK7). Graft maturation was assessed with double immunostaining of CK7 and insulin. Apoptosis was determined using propidium iodide staining. beta -cell proliferation in NPCCs was higher after 8 days of culture compared with that found in neonatal pig pancreas. After transplantation, beta -cell proliferation remained high at 10 days, decreased somewhat at 6 weeks, and was much lower 20 weeks after transplantation. Diabetic recipients not cured at 6 weeks after transplantation had significantly higher beta -cell proliferation compared with those cured and to normoglycemic recipients. The size of individual beta -cells, as determined by cross-sectional area, increased as the grafts matured. Graft insulin content was 20-fold increased at 20 weeks after transplantation compared with 8 days cultured NPCCs. The proliferation index of duct cells was significantly higher in neonatal pig pancreas than in 8 days cultured NPCCs and in 10-day-old grafts. The incidence of apoptosis in duct cells appeared to be low. About 20% of duct cells 10 days post transplantation showed costaining for CK7 and insulin, a marker of protodifferentiation. In conclusion, the increase in beta -cell mass after transplantation of NPCCs is due to both proliferation of differentiated beta -cells and differentiation of duct cells into beta -cells. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. NR 34 TC 52 Z9 52 U1 1 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 2001 VL 142 IS 5 BP 2115 EP 2122 DI 10.1210/en.142.5.2115 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 427YN UT WOS:000168434500052 PM 11316779 ER PT J AU Krahl, SE Senanayake, SS Handforth, A AF Krahl, SE Senanayake, SS Handforth, A TI Destruction of peripheral C-fibers does not alter subsequent vagus nerve stimulation-induced seizure suppression in rats SO EPILEPSIA LA English DT Article DE VNS; capsaicin; fibers; pentylenetetrazol; anticonvulsant; epilepsy ID CAPSAICIN; EPILEPSY; NEURONS AB Purpose: Early animal studies of the therapeutic mechanisms of vagus nerve stimulation (VNS) suggested that seizure suppression requires maximal activation of small, unmyelinated vagal C fibers. However, effective therapeutic stimulation parameters appear to be subthreshold for these fibers in humans, and there are no clinical reports of the autonomic side effects that would be expected if these fibers were maximally activated. We report here that selective destruction of C fibers with capsaicin does not affect VNS-induced seizure suppression in rats. Methods: Rats were pretreated with capsaicin or vehicle in three injections over a 2-day period. A cuff electrode was later implanted on the left cervical vagus nerve. Two days after surgery. VNS was given to half of the capsaicin- and vehicle- treated rats. The remaining rats were connected to the stimulator bur. did not receive VNS. Thirty seconds after VNS onset, seizures were induced by pentylenetetrazol (PTZ), and seizure severity was measured. Two days later, the reciprocal VNS treatment was: given, and PTZ-induced seizure severity was again measured. Results: VNS effectively reduced seizure severity in both capsaicin- and vehicle-treated rats as compared with their non-VHS baselines. Conclusions: These results indicate that activation of vagal C fibers is not necessary for VNS-induced seizure suppression. C1 VA Greater Los Angeles Healthcare Syst, Neurol Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Div Neurosurg, Los Angeles, CA USA. RP Krahl, SE (reprint author), VA Greater Los Angeles Healthcare Syst, Neurol Serv, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 14 TC 90 Z9 94 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY PY 2001 VL 42 IS 5 BP 586 EP 589 DI 10.1046/j.1528-1157.2001.09700.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 434VV UT WOS:000168837300002 PM 11380564 ER PT J AU Holmes, LB Pierce, MW AF Holmes, LB Pierce, MW TI Discussion: Assessment of teratogenic risk design and status of the North American Antiepileptic drug registry SO EPILEPSY RESEARCH LA English DT Editorial Material C1 Pfizer Global Res & Dev, Ann Arbor, MI 48105 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pierce, MW (reprint author), Pfizer Global Res & Dev, 2800 Plymouth Rd, Ann Arbor, MI 48105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAY PY 2001 VL 45 IS 1-3 SI SI BP 175 EP 176 DI 10.1016/S0920-1211(01)00249-2 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 442RF UT WOS:000169298200046 ER PT J AU Sayin, U Rutecki, PA Mellanby, J Sutula, TP AF Sayin, U Rutecki, PA Mellanby, J Sutula, TP TI Gamma-vinyl GABA reduces paired pulse inhibition in the rat dentate gyrus in vivo and in vitro SO EPILEPSY RESEARCH LA English DT Article DE vigabatrin; GABA; hippocampus; inhibition; dentate gyrus; GVG ID ANTIEPILEPTIC DRUGS; SINGLE-BLIND; IN-VIVO; VIGABATRIN; SEIZURES; PHARMACOLOGY; BRAIN; HIPPOCAMPUS; GABAPENTIN; PENTYLENETETRAZOL AB Gamma vinyl GABA (GVG), an irreversible GABA transaminase inhibitor, has anticonvulsant effects. GVG increases GABA levels in the brain by blocking its degradation, and is presumed to enhance GABAergic inhibition, however, in some cases it exacerbates seizures. We investigated the effects of GVG in vivo and in vitro on paired pulse inhibition (PPI) recorded in the rat dentate gyrus (DG) evoked by perforant path stimulation. At 2.5 h and 24 h after administration of GVG (1 g/kg, i.p.), there was a loss of PPI at both 15- and 25-ms interpulse intervals (IPI). Activation of presynaptic GABA(B) autoreceptors could explain this in vivo effect. We therefore further investigated the effects of co-application of GVG with the GABA(B) antagonists 2-OH saclofen (saclofen) or CCP 35348 (CGP) on PPI in hippocampal slices by in vitro study. Bath application of GVG (400 and 500 muM) not only resulted in a loss of perforant path evoked PPI at a 15-ms IPI, but produced facilitation of the second population spike relative to the first. Go-application of saclofen (250 muM) with GVG (500 muM) prevented facilitation of the second response of a paired-pulse. The facilitation of the second stimulation response produced by GVG (400 muM) was converted to inhibition by bath application of CGP 35348 (400 muM). These results suggest that activation of presynaptic GABA(B) receptors by increased extracellular GABA may be one of the contributing factors to the apparent paradoxical effect of GVG on PPI in the DG. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Wisconsin Hosp & Clin, Dept Neurol, Madison, WI 53792 USA. Univ Wisconsin Hosp & Clin, William S Middleton Mem Vet Adm Hosp, Neurosci Training Program, Dept Neurol, Madison, WI 53792 USA. Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. Univ Wisconsin, Dept Anat, Madison, WI 53706 USA. Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. RP Sayin, U (reprint author), Univ Wisconsin Hosp & Clin, Dept Neurol, H6-574,600 Highland Ave, Madison, WI 53792 USA. FU NINDS NIH HHS [NS25020, NS 28580] NR 39 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAY PY 2001 VL 44 IS 2-3 BP 109 EP 117 DI 10.1016/S0920-1211(01)00200-5 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 438YE UT WOS:000169081200003 PM 11325567 ER PT J AU Antman, EM de Lemos, JA Braunwald, E AF Antman, EM de Lemos, JA Braunwald, E TI Epicardial flow and myocardial reperfusion following abciximab and low-dose thrombolytic therapy for acute myocardial infarction SO EUROPEAN HEART JOURNAL SUPPLEMENTS LA English DT Article; Proceedings Paper CT International Symposium on Early Intervention and Abciximab - Preserving Myocardium CY MAY 23-26, 2000 CL PARIS, FRANCE DE abciximab; GP IIb/IIIa receptor; TIMI 14; perfusion; microvascular; ST-segment resolution ID PLASMINOGEN-ACTIVATOR; CORONARY THROMBOLYSIS; PERFUSION PATTERNS; RETEPLASE; TRIAL; ALTEPLASE; RESISTANCE; RESOLUTION; EXTENT; LYSIS AB Recent evidence from the Thrombolysis in Myocardial Infarction (TIMI) 14 trial suggests that combining reduced-dose fibrinolytic therapy with the potent platelet inhibition afforded by a glycoprotein (GP) IIb/IIIa receptor antagonist can help overcome the limitations of fibrinolytic therapy alone. The TIMI 14 investigators found that low-dose alteplase in combination with abciximab significantly increased the incidence of TIMI 3 flow at 60 and 90 min compared with full-dose alteplase. The use of abciximab emerged as one of the three principal determinants of TIMI 3 flow, along with time to treatment and location of the occlusive thrombus. Complete ST-segment resolution, reflecting perfusion at the myocardial tissue level, was a significant predictor of 30-day survival in the TIMI 14 study. Patients treated with abciximab plus reduced-dose fibrinolytic therapy had significantly greater median ST-segment resolution and a significantly higher rate of complete ST-segment resolution than patients given fibrinolytic therapy alone. Similar benefits were observed in TIMI 14 patients who underwent early adjunctive percutaneous coronary intervention following combined therapy with abciximab and reduced-dose fibrinolysis. These findings indicate that a strategy coupling abciximab with reduced-dose fibrinolytic therapy not only enhances epicardial flow but also improves myocardial reperfusion following acute myocardial infarction. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 75 Francis St, Boston, MA 02115 USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1520-765X J9 EUR HEART J SUPPL JI Eur. Heart J. Suppl. PD MAY PY 2001 VL 3 IS A BP A8 EP A13 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 436PP UT WOS:000168944500003 ER PT J AU Grossman, SR AF Grossman, SR TI p300/CBP/p53 interaction and regulation of the p53 response SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Review DE p53; p300; CBP; transactivation; degradation; acetylation; MDM2 ID CELL-CYCLE ARREST; DNA-DAMAGE; TRANSCRIPTIONAL ADAPTER; TUMOR-SUPPRESSOR; PROTEIN P300; MDM2; PHOSPHORYLATION; E1A; CBP; ACTIVATION AB Substantial evidence points to a critical role for the p300/CREB binding protein (CBP) coactivators in p53 responses to DNA damage. p300/CBP and the associated protein P/CAF bind to and acetylate p53 during the DNA damage response, and are needed for full p53 transactivation as well as downstream p53 effects of growth arrest and/or apoptosis. Beyond this simplistic model, p300/CBP appear to be complex integrators of signals that regulate p53, and biochemically, the multipartite p53/p300/CBP interaction is equally complex. Through physical interaction with p53, p300/CBP can both positively and negatively regulate p53 transactivation, as well as p53 protein turnover depending on cellular context and environmental stimuli, such as DNA damage. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grossman, SR (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 50 TC 138 Z9 144 U1 3 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD MAY PY 2001 VL 268 IS 10 BP 2773 EP 2778 DI 10.1046/j.1432-1327.2001.02226.x PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 437AP UT WOS:000168968300003 PM 11358491 ER PT J AU Ellisen, LW Palmer, RE Maki, RG Truong, VB Tamayo, P Oliner, JD Haber, DA AF Ellisen, LW Palmer, RE Maki, RG Truong, VB Tamayo, P Oliner, JD Haber, DA TI Cascades of transcriptional induction during human lymphocyte activation SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE gene expression profiling; cluster analysis; lymphocyte activation; signal transduction; transcription factors ID HUMAN T-CELLS; NF-KAPPA-B; GENE-EXPRESSION; INDUCED APOPTOSIS; RECEPTOR; ALPHA; DIFFERENTIATION; INTERLEUKIN-1; FRACTALKINE; PHOSPHATASE AB Lymphocyte activation is known to be associated with the induction of genes implicated in cytokine signaling and cellular proliferation. High-density microarrays offer the means to monitor global cellular expression profiles, temporal relationships between classes of transcripts, and alterations associated with human disease or immunosuppression, We sought to determine whether microarray analysis would accurately reflect the normal pattern of gene expression following human T cell activation, and whether the complex expression patterns identified could be analyzed to produce a functional profile of lymphocyte activation. We examined a time course of sequential expression profiles for 6800 cellular transcripts in human lymphocytes activated with concanavalin A. Expression patterns were grouped using clustering analysis and validated using Northern blotting. Genes known to be induced following T cell activation were accurately identified, and the qualitative patterns of gene expression were well correlated between Northern and microarray analyses. Quantitative differences in gene expression levels were less well correlated between these two techniques, Expression profile analysis revealed the sequential induction of groups of functionally similar genes, whose temporal coregulation underscores known cellular events during T cell activation, This functional "fingerprint" of lymphocyte activation may prove useful for comparisons of lymphocyte responses under experimental conditions and in disease states. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Affymetrix, Santa Clara, CA 95051 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA58596, CA82831] NR 36 TC 26 Z9 27 U1 0 U2 1 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAY PY 2001 VL 80 IS 5 BP 321 EP 328 DI 10.1078/0171-9335-00162 PG 8 WC Cell Biology SC Cell Biology GA 444DZ UT WOS:000169384900001 PM 11432721 ER PT J AU Tateno, H Nakamura, H Minematsu, N Amakawa, K Terashima, T Fujishima, S Luster, AD Lilly, CM Yamaguchi, K AF Tateno, H Nakamura, H Minematsu, N Amakawa, K Terashima, T Fujishima, S Luster, AD Lilly, CM Yamaguchi, K TI Eotaxin and monocyte chemoattractant protein-1 in chronic eosinophilic pneumonia SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE bronchoalveolar lavage; chronic eosinophilic pneumonia; eotaxin; interleukin-5; interstitial lung disease; monocyte chemoattractant protein-1 ID ACTIVATED T-CELLS; BRONCHOALVEOLAR LAVAGE; ALLERGIC INFLAMMATION; AIRWAY HYPERRESPONSIVENESS; LUNG-DISEASES; CHEMOKINES; EXPRESSION; CYTOKINES; IL-5; ASTHMA AB Chronic eosinophilic pneumonia (CEP) is characterized by chronic or recurrent pulmonary infiltrates with eosinophils, but the precise mechanism of eosinophil accumulation has not been fully elucidated. Eotaxin is one of the CC chemokines that selectively recruits eosinophils and contributes to the pathogenesis of allergic airway diseases including asthma, but its roles in pathogenesis of CEP have not been fully elucidated. The authors measured concentrations of eotaxin and other CC chemokines monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted, macrophage inflammatory protein-la, and the eosinophil activating Th2 cytokine interleukin (IL)-5 in bronchoalveolar lavage (BAL) fluid from CEP patients (n=11), and compared these concentrations with those from control subjects (n=6). The eotaxin (904 +/- 203 versus 29 +/-7 pg.mL(-1), p=0.0001), MCP-1 (194 +/- 57 versus 15 +/-2 pg.mL(-1), p <0.05), and IL-5 (7.8 +/-2.0 versus 2.7 +/-0.6 pg.mL(-1), p <6.05) levels,were significantly higher for cases with CEP in comparison to those serving as controls. Proportions of eosinophil and lymphocyte counts were greater in BAL fluid from CEP patients. Eotaxin and IL-5 levels correlated with the proportion of eosinophils in BAL fluid from CEP patients. MCP-I correlated with the relative lymphocyte numbers. In short, eotaxin, interleukin-5, and monocyte chemoattractant protein-1 levels were higher in the BAL fluid of CEP patients and these levels may contribute to eosinophil and lymphocyte recruitment and activation in the airways as found with this disorder. C1 Keio Univ, Sch Med, Dept Med, Cardiopulm Div,Shinjuku ku, Tokyo 1608582, Japan. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Nakamura, H (reprint author), Keio Univ, Sch Med, Dept Med, Cardiopulm Div,Shinjuku ku, 35 Shinanomachi, Tokyo 1608582, Japan. RI Fujishima, Seitaro/G-6155-2011 OI Fujishima, Seitaro/0000-0001-8823-8440 NR 26 TC 20 Z9 21 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146, WEST ST, STE 2.4 HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD MAY PY 2001 VL 17 IS 5 BP 962 EP 968 DI 10.1183/09031936.01.17509620 PG 7 WC Respiratory System SC Respiratory System GA 458RU UT WOS:000170209000021 PM 11488333 ER PT J AU Shomer, NH Dangler, CA Schrenzel, MD Whary, MT Xu, SL Feng, Y Paster, BJ Dewhirst, FE Fox, JG AF Shomer, NH Dangler, CA Schrenzel, MD Whary, MT Xu, SL Feng, Y Paster, BJ Dewhirst, FE Fox, JG TI Cholangiohepatitis and inflammatory dowel disease induced by a novel urease-negative Helicobacter species in A/J and Tac : ICR : HascidfRF mice SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE Helicobacter; mouse; typhlocolitis; cholangiohepatitis ID CHRONIC ACTIVE HEPATITIS; BOWEL-DISEASE; SCID MICE; SP-NOV; CAMPYLOBACTER-CINAEDI; BACTERIAL-INFECTION; INTESTINAL FLORA; PYLORI; BILIS; MOUSE AB Helicobacter bills and H. hepaticus, both urease-positive intestinal helicobacters of mice, have been shown experimentally to induce proliferative typhlocolitis in scid mice. We recently isolated a urease-negative Helicobacter sp. (H. sp.) that also induced proliferative typhlocolitis in pilot studies in scid mice, To determine the pathogenic potential of H. sp, in immunocompromised and immunocompetent mice, 5-week old male A/J or Tac:lcr:Ha(ICR)-scidfRF mice were inoculated by intraperitoneal (IP) injection with similar to 3 x 10(7) colony-forming units (CFU) of H. so, Mice were necropsied at various time points postinoculation (PI), Sham-inoculated mice had no clinical, gross, or histopathological lesions, In contrast, scid mice inoculated IP with H. sp. had severe hemorrhagic diarrhea and decreased weight gain at 2, 7, and 18 weeks postinoculation (PI), with severe proliferative typhlocolitis, phlebothrombosis, and hepatitis. A/J mice had no clinical signs, but had mild to moderate proliferative typhlocolitis and moderate to marked cholangiohepatitis at 7 and 24 weeks PI, A/J mice infected with H. sp. developed robust immune responses of a predominant Th1 type. This report demonstrates that infection with a urease-negative helicobacter can cause inflammatory bower disease (IBD) and hepatitis in scid and immunocompetent A/J mice, These results provide a new model of IBD and cholangiohepatitis associated with a specific urease-negative, novel H. species. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Room 825C, Cambridge, MA 02139 USA. FU NCI NIH HHS [P01CA26731, R01CA67529]; NIDDK NIH HHS [R01DK52413] NR 40 TC 21 Z9 21 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 MAY PY 2001 VL 226 IS 5 BP 420 EP 428 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 429XD UT WOS:000168542500005 PM 11393169 ER PT J AU Yates, KE Mizuno, S Glowacki, J AF Yates, KE Mizuno, S Glowacki, J TI Early shifts in gene expression during chondroinduction of human dermal fibroblasts SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE chondroinduction; chondroblast; differentiation; cytoskeleton; demineralized bone; 3-D collagen sponge; human fibroblast ID REPRESENTATIONAL DIFFERENCE ANALYSIS; HUMAN VIGILIN GENE; CHROMOSOMAL LOCALIZATION; DEMINERALIZED BONE; TRANSFER-RNA; 3-DIMENSIONAL CULTURE; BINDING PROTEIN; JOINT FORMATION; MESSENGER-RNA; VI COLLAGEN AB Treatment options for damaged articular cartilage are limited because of that. tissue's poor capacity for repair. Possible approaches to this problem are to stimulate, cartilage matrix production in situ or to engineer replacement tissue. Both of these approaches would benefit from a detailed understanding of the molecular mechanisms of chondroblast differentiation, In previous studies, we described a novel in vitro model of postnatal chondroblast differentiation. That model of induced chondrogenesis was used to test the hypothesis that cellular interactions with demineralized bone powder (DBP) would induce specific, early shifts in gene expression, prior to the expression of cartilage matrix genes. Differentially expressed genes were identified by representational difference analysis of human dermal fibroblasts cultured for 3 days with DBP in three-dimensional collagen sponges. Genes that were upregulated by DBP comprised several functional classes, including cytoskeletal elements, protein synthesis and trafficking, and transcriptional regulation. kinetic analysis of gene expression over 21 days showed that vigilin was transiently upregulated on day 3. In contrast, expression of cartilage signature genes continued to increase. These results are an important step toward complete characterization of the mechanisms by which DBP induces chondroblastic differentiation in postnatal cells. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Yates, KE (reprint author), Massachusetts Gen Hosp, Skeletal Biol Res Ctr, 149 13th St,Code 5031, Charlestown, MA 02129 USA. FU NIAMS NIH HHS [AR44873] NR 50 TC 22 Z9 26 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 2001 VL 265 IS 2 BP 203 EP 211 DI 10.1006/excr.2001.5192 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 427YM UT WOS:000168434400003 PM 11302685 ER PT J AU Mashour, GA Moulding, HD Chalavi, A Khan, GA Rabkin, SD Martuza, RL Driever, PH Kurtz, A AF Mashour, GA Moulding, HD Chalavi, A Khan, GA Rabkin, SD Martuza, RL Driever, PH Kurtz, A TI Therapeutic efficacy of G207 in a novel peripheral nerve sheath tumor model SO EXPERIMENTAL NEUROLOGY LA English DT Article DE nerve sheath tumors; neuroblastoma; neurofibromatosis; viral therapy; HSV ID HERPES-SIMPLEX VIRUS; NEUROFIBROMATOSIS TYPE-1; MALIGNANT GLIOMAS; NF1 GENE; NEUROBLASTOMA; MOUSE; MUTANT; GROWTH; CELLS AB Nerve involvement poses a significant obstacle for the management of peripheral nervous system tumors, and nerve injury provides a frequent source of postoperative morbidity, The lack of suitable animal models for peripheral nerve tumors has impeded the development of alternative nerve-sparing therapies. To evaluate the effect of a multimutated replication-competent herpes simplex virus (G207) on the growth of peripheral nerve tumors and on nerve function, we developed a novel peripheral nerve sheath tumor model. Human neuroblastoma-derived cells injected into murine sciatic nerve consistently caused tumor development within the nerve sheath after 2 weeks followed by increasingly severe impairment of nerve function. Tumor treatment by a single intratumoral injection of G207 resulted in significant reduction of functional impairment, inhibition of tumor growth and prolonged survival. Direct injection of G207 viral particles into the healthy nerve sheath caused no obvious neurologic sequelae, whereas injections of wildtype virus resulted in uniform lethality. The results indicate that viral therapy might be considered as a safe alternative to surgical removal of tumors with peripheral nerve involvement. (C) 2001 Academic Press. C1 Georgetown Univ, Dept Neurosurg, Washington, DC 20007 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Mashour, GA (reprint author), Georgetown Univ, Dept Neurosurg, 3970 Reservoir Rd NW, Washington, DC 20007 USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NINDS NIH HHS [R29NS37895-01] NR 33 TC 18 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2001 VL 169 IS 1 BP 64 EP 71 DI 10.1006/exnr.2001.7641 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 431KD UT WOS:000168629600008 PM 11312559 ER PT J AU Iwakiri, D Podolsky, DK AF Iwakiri, D Podolsky, DK TI Keratinocyte growth factor promotes goblet cell differentiation through regulation of goblet cell silencer inhibitor SO GASTROENTEROLOGY LA English DT Article ID INTESTINAL TREFOIL FACTOR; INFLAMMATORY BOWEL-DISEASE; FACTOR GENE; MOLECULAR-CLONING; HOMEOBOX GENE; EXPRESSION; PROTEIN; IDENTIFICATION; TRANSCRIPTION; SEQUENCE AB dBackground & Aims: Keratinocyte growth factor (KGF) is an epithelial cell-specific growth factor. Previous reports demonstrated that HGF induces differentiation of epithelial cells of gastrointestinal tract in vivo, especially goblet cell-specific lineage stimulation. Intestinal trefoil factor (ITF) is selectively expressed in intestinal goblet cells and its expression correlates with intestinal goblet cell differentiation. In this study, we analyzed the mechanism of HGF modulation of goblet cell differentiation through characterization of its effects on ITF gene expression. Methods: Subclone H2 of the human colonic epithelial cell line HT-29, which can be induced to intestinal goblet cells, was treated with KGF and characterized by Northern and Western blot analyses, transient transfection assays, and electrophoretic mobility shift assays (EMSAs). Results: KGF promoted differentiation of H2 cells to goblet cells as reflected by induced ITF expression, Transient transfection assays revealed that HGF regulates mouse ITF transcription through the goblet cell silencer inhibitor (GCSI) element, which is essential for goblet cell-specific expression of ITF. EMSAs showed that KGF induces GCSI binding protein (GCSI-BP). Conclusions: HGF promotes goblet cell differentiation through the induction of GCSI-BP, a goblet cell-specific transcription factor. GCSI-BP may play a central role in intestinal goblet cell differentiation. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Iwakiri, D (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43351, DK46906] NR 38 TC 45 Z9 46 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2001 VL 120 IS 6 BP 1372 EP 1380 DI 10.1053/gast.2001.24029 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 439LX UT WOS:000169119300011 PM 11313307 ER PT J AU Faigel, DO AF Faigel, DO TI EUS in patients with benign and malignant lymphadenopathy SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT EUS 2000 Meeting CY 2000 CL MONTE CAROL, MONACO ID FINE-NEEDLE ASPIRATION; LYMPH-NODE METASTASES; ENDOSCOPIC ULTRASONOGRAPHY; ESOPHAGEAL CANCER; ULTRASOUND; ACCURACY; ENDOSONOGRAPHY; CARCINOMA; DIAGNOSIS; FEATURES AB Background: The EUS appearance of lymph nodes in patients undergoing evaluation for malignancy was studied. Methods: In 378 patients EUS characteristics were assessed: size of tumor, largest lymph node size, number of lymph nodes, distance of lymph nodes from the tumor, and on a 5-point visual analogue scale(1 = least malignant to 5 = most malignant), roundness, homogeneity, and echogenicity, A morphology score (sum of roundness, homogeneity, and echogenicity) was calculated. Findings were compared with fine needle aspiration or surgical histopathology in 238 patients. Results: When using multivariate analysis, only lymph node size (1.4 +/- 0.1 cm vs. 1.7 +/- 0.1 cm, p = 0.001), distance from tumor (3.1 +/- 0.4 cm vs. 1.6 +/- 0.4 cm, p = 0.013), and morphology score (9.9 +/- 0.3 vs. 11.9 +/- 0.3, p = 0.001) for benign versus malignant lymph nodes (mean +/- SEM) were significant. Lymph node size was significant for esophageal cancer (p = 0.006) and other mediastinal lymph nodes (p = 0.007) but not for pancreaticobiliary malignancies (p = 0.1) or celiac lymph nodes (p = 0.4). Distance from the tumor was significant for pancreaticobiliary (p = 0.01) but not esophageal cancers (p = 0.7). Morphology was significant for all sites. The presence of at least one lymph node of 1 cm or greater within 1 cm of the tumor and with a morphology score of 14 or greater had a positive predictive value of 81% (prevalence = 13%). A morphology score of 6 or less had a negative predictive value of 92% (prevalence = 12%). Conclusions: Patients with malignant adenopathy have lymph nodes that are larger, closer to the primary tumor, rounder, darker, and more homogeneous than those of patients without malignant adenopathy. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Med, Div Gastroenterol, Portland, OR 97201 USA. RP Faigel, DO (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Med, Div Gastroenterol, P3G1,3710 SW Vet Hosp Rd, Portland, OR 97201 USA. NR 23 TC 53 Z9 55 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAY PY 2001 VL 53 IS 6 BP 593 EP 598 DI 10.1067/mge.2001.114060 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 428DN UT WOS:000168446200010 PM 11323584 ER PT J AU Kommoss, F Oliva, E Young, RH Bittinger, F Kirkpatrick, CJ Schmidt, D AF Kommoss, F Oliva, E Young, RH Bittinger, F Kirkpatrick, CJ Schmidt, D TI Expression of mullerian inhibiting substance, CD99 and HEA125 in ovarian tumors SO GEBURTSHILFE UND FRAUENHEILKUNDE LA English DT Article ID GRANULOSA-CELL TUMORS; CORD-STROMAL TUMORS; MESSENGER-RIBONUCLEIC-ACID; SURFACE GLYCOPROTEIN; MR 34,000; MARKER; CARCINOMA; ANTIBODY; ORIGIN; ALPHA AB Objective: The expression of Mullerian inhibiting substance (MIS), CD99 (MIC-2 gene product), and HEA125 in ovarian tumors is potentially useful for diagnostic purposes. Methods: We studied the expression of MIS, CD99, and an epithelial cell-associated antigen recognized by antibody HEA125 in a series of 179 ovarian tumors using monoclonal or polyclonal antibodies and standard immunohistochemical techniques. Results: MIS was consistently detected in primary and metastatic sex cord tumors with annular tubules (SCTAT) (n=9). 3 of 9 adult granulosa cell tumors (AGCT) 4 of 8 juvenile granulosa cell tumors (JGCT), 3 of 9 Sertoli cell tumors (SCT), 2 of 2 unclassified sex cord tumors, 2 of 7 steroid cell tumors, 1 of 1 gonadoblastoma (sex cord cells positive, germ cells negative), 3 of S female adnexal tumors of probable wolffian origin (FATPWO), and 2 of 4 small cell carcinomas of the hypercalcemic type (SCCHCT) were also MIS positive. In contrast, 9 thecomas, 10 fibromas, 10 fibrosarcomas, S sclerosing stromal tumors (SST), and 6 Sertoli-Leydig cell tumors (SLCT) were MIS negative. All 11 primary and metastatic JGCT were CD19 positive. In addition, 1 of 13 AGCTs, 3 of II thecomas, 3 of II SSTs, 3 of 11 SCTs, 2 of 10 SLCTs, 2 of 12 SCTATs, 1 of 1 gynandroblastoma, 1, of 2 unclassified sex cord tumors, and 4 of 12 SCCHCTs were also CD99 positive. However, 11 fibromas, 10 fibrosarcomas, 9 steroid cell tumors, 5 gonadoblastomas, and 10 FATPWOs were CD99 negative. Likewise, except for weak focal CD99 immunostaining in 1 of 3 yolk sac tumors (YST), all 16 remaining germ cell tumors and all 18 borderline or malignant epithelial-stromal tumors were negative. HEA125 immunoreactivity was detected in 2 of 11 thecomas, 1 of 11 SCTs, 4 of 10 SLCTs, 1 of 2 unclassified sex cord tumors, 1 of 10 FATPWOs, 4 of 12 SCCHCTs as well as in most germ cell tumors and epithelial-stromal tumors. 13 AGCTs, 11 JGCTs, 11 fibromas, 10 fibrosarcomas, 11 SSTs, 12 SCTATs, 1 gynandroblastoma, 9 steroid cell tumors, and 5 gonadoblastomas were HEA125 negative. Conclusion: Our findings indicate that MIS is a marker of sex-cord differentiation and may be useful as a serum tumor marker for certain sex cord tumors, especially SCTAT. Although the detection of MIS and CD99 in some SCCHCTs and FATPWOs might argue in favor of a sex cord origin, the histogenesis of these tumors remains unclear. Although inhibin-cr has previously been shown to be a more sensitive marker of sex-cord differentiation, a panel of immunohistochemical markers including MIS, CD99 and HEA125 may be helpful in the differential diagnosis of certain ovarian neoplasms. C1 Referenzzentrum Gynakopathol, Inst Pathol, D-68159 Mannheim, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Kliniken Mainz, Inst Pathol, Mainz, Germany. RP Kommoss, F (reprint author), Referenzzentrum Gynakopathol, Inst Pathol, A2,2, D-68159 Mannheim, Germany. NR 25 TC 4 Z9 4 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0016-5751 J9 GEBURTSH FRAUENHEILK JI Geburtshilfe Frauenheilkd. PD MAY PY 2001 VL 61 IS 5 BP 274 EP 279 DI 10.1055/s-2001-14147 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 432WK UT WOS:000168718600005 ER PT J AU Chaturvedi, P Warren, CD Altaye, M Morrow, AL Ruiz-Palacios, G Pickering, LK Newburg, DS AF Chaturvedi, P Warren, CD Altaye, M Morrow, AL Ruiz-Palacios, G Pickering, LK Newburg, DS TI Fucosylated human milk oligosaccharides vary between individuals and over the course of lactation SO GLYCOBIOLOGY LA English DT Article DE human milk; oligosaccharide; lactation; HPLC ID RAT SMALL-INTESTINE; ESCHERICHIA-COLI; NONIMMUNOGLOBULIN FRACTION; DEVELOPMENTAL-CHANGES; CELLS; INHIBITION; COMPONENTS; COLOSTRUM; ADHESION; IDENTIFICATION AB Specific human milk oligosaccharides, especially fucosylated neutral oligosaccharides, protect infants against specific microbial pathogens. To study the concentrations of individual neutral oligosaccharides during lactation, a total of 84 milk samples were obtained from 12 women at 7 time periods during weeks 1-49 postpartum. The neutral oligosaccharides from each sample were isolated, perbenzoylated, resolved, and quantified by reversed-phase highperformance liquid chromatography, The resultant oligosaccharide peaks, identified by co-elution with authentic standards and mass spectrometry, ranged in size from trito octasaccharides, The total concentration of oligosaccharides declined over the course of lactation; the mean concentration at 1 year was less than half that in the first few weeks postpartum One of the 12 donors produced milk fucosyloligosaccharides that were essentially devoid of alpha1,2 linkages (but contained alpha1,3- and alpha1,4-linked fucose) until late in lactation, consistent with the nonsecretor phenotype, In milk samples from the remaining 11 donors, fucosyloligosaccharides containing alpha1,2-linked fucose were prevalent, and their profiles were distinct from those of fucosyloligosaccharides devoid of alpha1,2-linked fucose, The ratio of al,2-linked oligosaccharide concentrations to oligosaccharides devoid of al,2-1inked fucose changed during the first year of lactation from 5:1 to 1:1, Furthermore, the absolute and the relative concentrations of individual oligosaccharides varied substantially, both between individual donors and over the course of lactation for each individual. The patterns of milk oligosaccharides among individuals suggest the existence of many genotype subpopulations. This variation in individual oligosaccharide concentrations suggests that the protective activities of human milk could also vary among individuals and during lactation. C1 Shriver Ctr Mental Retardat, Waltham, MA 02452 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Eastern Virginia Med Sch, Norfolk, VA 23510 USA. Inst Nacl Ciecias Med & Nutr, Mexico City 14000, DF, Mexico. RP Newburg, DS (reprint author), Shriver Ctr Mental Retardat, Waltham, MA 02452 USA. RI Altaye, Mekibib/N-5274-2015 FU NICHD NIH HHS [HD 13021] NR 37 TC 150 Z9 162 U1 10 U2 30 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD MAY PY 2001 VL 11 IS 5 BP 365 EP 372 DI 10.1093/glycob/11.5.365 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 447HV UT WOS:000169566600005 PM 11425797 ER PT J AU Tillmann, HL Chen, DF Trautwein, C Kliem, V Grundey, A Berning-Haag, A Boker, K Kubicka, S Pastucha, L Stangel, W Manns, MP AF Tillmann, HL Chen, DF Trautwein, C Kliem, V Grundey, A Berning-Haag, A Boker, K Kubicka, S Pastucha, L Stangel, W Manns, MP TI Low frequency of HLA-DRBI*11 in hepatitis C virus induced end stage liver disease SO GUT LA English DT Article DE hepatitis C; HLA; liver cirrhosis; immunogenetics; hepatocellular carcinoma; genotype ID POLYMERASE CHAIN-REACTION; ANTI-D IMMUNOGLOBULIN; CLASS-II GENOTYPE; VIRAL CLEARANCE; HLA ANTIGENS; RNA LEVELS; B VIRUS; INFECTION; ASSOCIATION; ALLELES AB Hepatitis C virus (HCV) infection becomes chronic in more than 70% of patients, leading to endstage liver disease in about 20-30% of these patients. Apart from the virus itself,host factors that modulate the immune response are likely to be involved in determining the outcome of HCV infection. Studies on the association of human leucocyte antigens (HLAs) and HCV infection have shown inconsistent results. Selection of patient subgroups may be crucial. However, any association relevant to HCV disease progression will become evident, especially in those patients with end stage liver disease. Therefore, we analysed the phenotype frequencies of HLA antigens in two groups of 69 and 39 patients with HCV induced liver cirrhosis who had received a transplant or were awaiting liver transplantation, The first group was typed serologically and compared with 331 blood and Liver donors. The second; group, prospectively HLA typed by a polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) procedure for HLA-DRB and DQB alleles, was compared with another 170 PCR-SSO typed and randomly selected blood donors. Decreased frequencies for HLA-DR5 and HLA-DQ3 were found in one group of patients with HCV induced liver cirrhosis compared with the control groups. In the second analysis comparing 39 patients with end stage liver cirrhosis with blood donors, we confirmed the significant decrease in HLA-DRB1*11 and HLA-DQB1*03, which corresponded to serological HLA-DR5 and HLA-DQ3 antigens, respectively. Our results show that the presence of HLA-DRB1*11 and HLA-DQB1*03 alleles is associated with a reduced risk for the development of HCV induced end stage liver disease. C1 Med Hsch Hannover, Dept Gastroenterol & Hepatol, D-30625 Hannover, Germany. Med Hsch Hannover, Dept Transfus Med, D-30625 Hannover, Germany. Med Hsch Hannover, Dept Nephrol, D-30625 Hannover, Germany. Ctr Blood Res, HLA Lab, Boston, MA 02115 USA. RP Manns, MP (reprint author), Med Hsch Hannover, Dept Gastroenterol & Hepatol, Carl Neuberg Str 1, D-30625 Hannover, Germany. NR 52 TC 43 Z9 44 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD MAY PY 2001 VL 48 IS 5 BP 714 EP 718 DI 10.1136/gut.48.5.714 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 425XR UT WOS:000168317400028 PM 11302974 ER PT J AU Campos, SM Penson, RT Mays, AR Berkowitz, RS Fuller, AF Goodman, A Matulonis, UA Muzikansky, A Seiden, MV AF Campos, SM Penson, RT Mays, AR Berkowitz, RS Fuller, AF Goodman, A Matulonis, UA Muzikansky, A Seiden, MV TI The clinical utility of liposomal doxorubicin in recurrent ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-18, 1999 CL ATLANTA, GEORGIA SP Amer Soc Clin Oncol DE ovarian cancer; liposomal doxorubicin; Doxil; HER-2/neu; recurrent disease; cardiac toxicity ID PLATINUM-RESISTANT; ORAL ETOPOSIDE; POLYETHYLENE-GLYCOL; PHASE-II; PACLITAXEL; CARCINOMA; THERAPY; TOPOTECAN; ONCOGENE; BREAST AB Objectives. The aim of this study was to determine the efficacy and toxicity of single agent off-protocol, liposomal doxorubicin (Doxil Alza), in consecutive patients with recurrent ovarian cancer and to investigate the influence of HER-2/neu expression on response to liposomal doxorubicin, Patients and methods, Retrospective analysis of 72 consecutive patients treated, typically with liposomal doxorubicin 40 mg/m(2) q28 days between January 1997 and December 1998. Results. Twenty-nine patients (40%) had platinum- and taxane-resistant tumors. Nineteen patients (27%) responded with clinical or radiological evidence of response with reduction in CA-125 of > 50%. One complete response (CR) and 7 partial responses (PRs) occurred in platinum- and taxane-resistant patients (radiological response (RR) 29%) and 8 PRs occurred in patients with visceral metastases (RR 28%), Time to progression was 5.3 (2.1-12.1) months. Only 7 dose delays (3%) and 20 dose reductions (8%) were necessary in 265 cycles of treatment. Hematological toxicity was generally mild with grade (Gr) greater than or equal to III neutropenia in 1 (2%), Gr greater than or equal to III thrombocytopenia in 1 (1%), and Or greater than or equal to III anemia in 8 patients (11%). One patient (1%) was admitted with fever and neutropenia. Other toxicity was minimal with Gr greater than or equal to III mucositis occurring in 3 patients (4%), Gr greater than or equal to III cutaneous toxicity was seen in 6 patients (8%). Three patients (4%) had a > 10% fall in ejection fraction but there was no unequivocal clinical heart failure, Conclusions. The data suggest that liposomal doxorubicin is an active drug in both taxane- and platinum-sensitive and resistant recurrent ovarian cancer. Liposomal doxorubicin is associated with tolerable toxicity and is particularly well tolerated in patients with multiple prior lines of treatment. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Seiden, MV (reprint author), Div Hematol Oncol, Cox Bldg 640,100 Blossom St, Boston, MA 02114 USA. NR 31 TC 72 Z9 73 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 MAY PY 2001 VL 81 IS 2 BP 206 EP 212 DI 10.1006/gyno.2001.5980 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 431QV UT WOS:000168642800014 PM 11330951 ER PT J AU Katarincic, JA AF Katarincic, JA TI Thumb kinematics and their relevance to function SO HAND CLINICS LA English DT Article ID TRAPEZIOMETACARPAL JOINT AB The prehensile ability of the thumb enables intricate hand movements. Despite this dexterity, extremely high forces are transmitted across the thumb. Forces are magnified up to thirteen times from the thumb pulp to the trapeziometacarpal (TM) joint. A knowledge of the bony anatomy, ligamentous anatomy, and musculotendinous forces across the TM joint help to explain the stability of the thumb during these activities. C1 Mayo Med Sch, Dept Orthopaed Surg, Rochester, MN USA. Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. RP Katarincic, JA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 16 TC 20 Z9 20 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 0749-0712 J9 HAND CLIN JI Hand Clin. PD MAY PY 2001 VL 17 IS 2 BP 169 EP + PG 7 WC Orthopedics SC Orthopedics GA 456TJ UT WOS:000170098100003 PM 11478039 ER PT J AU Ring, D Herndon, JH AF Ring, D Herndon, JH TI Implant arthroplasty of the metacarpophalangeal joint of the thumb SO HAND CLINICS LA English DT Article AB Thumb metacarpophalangeal arthritis may affect overall hand function more than expected because pain and instability compromise pinch and grip strength. Implant arthroplasty represents one option in the treatment of deformity destruction, and instability at the metacarpophalangeal joint level. Appropriate use of implant arthroplasty requires careful evaluation of the overall deformity and the status of the interphalangeal joint. If the interphalangeal joint is likely to require fusion-either simultaneous with metacarpophalangeal surgery or subsequently-then implant arthroplasty may be the best treatment option for the metacarpophalangeal joint. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hand Surg Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), 11 Hancock St 4, Boston, MA 02114 USA. NR 13 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 0749-0712 J9 HAND CLIN JI Hand Clin. PD MAY PY 2001 VL 17 IS 2 BP 271 EP + PG 4 WC Orthopedics SC Orthopedics GA 456TJ UT WOS:000170098100013 PM 11478049 ER PT J AU Schouten, R AF Schouten, R TI Law and psychiatry: What should our residents learn? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article C1 Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. RP Schouten, R (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, Fruit St, Boston, MA 02114 USA. NR 2 TC 6 Z9 6 U1 1 U2 3 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 MAY-JUN PY 2001 VL 9 IS 3 BP 136 EP 138 DI 10.1080/713854866 PG 3 WC Psychiatry SC Psychiatry GA 426TM UT WOS:000168364500005 PM 11287408 ER PT J AU Mohr, L Yoon, SK Eastman, SJ Chu, Q Scheule, RK Scaglioni, PP Geissler, M Heintges, T Blum, HE Wands, JR AF Mohr, L Yoon, SK Eastman, SJ Chu, Q Scheule, RK Scaglioni, PP Geissler, M Heintges, T Blum, HE Wands, JR TI Cationic liposome-mediated gene delivery to the liver and to hepatocellular carcinomas in mice SO HUMAN GENE THERAPY LA English DT Article ID CYTOSINE DEAMINASE GENE; THYMIDINE KINASE GENE; TRANSFER IN-VIVO; MOUSE-LIVER; RECOMBINANT ADENOVIRUSES; DNA DELIVERY; PLASMID DNA; THERAPY; EXPRESSION; CELLS AB The potential of cationic liposomes as nonviral vectors for in vivo gene delivery to the liver and to intrahepatic hepatocellular carcinoma (HCC) was investigated. Mice were injected via the tail vein or portal vein with a cationic lipid complexed to plasmid DNA (pDNA) encoding the chloramphenicol acetyltransferase (CAT) reporter gene at various cationic lipid:pDNA molar ratios to analyze the efficiency of gene delivery after intravenous administration. Tail vein injection resulted in high CAT expression levels in lung and spleen and low levels in the liver. Portal vein injection, by comparison, significantly enhanced hepatic reporter gene expression but also resulted in pronounced hepatic toxicity. Gene delivery to intrahepatic tumors produced by intrahepatic injection of human HCC cells was analyzed in nude mice. Tail vein injection as well as portal vein injection resulted in low levels of gene expression in intrahepatic tumors. By comparison, high levels of gene expression were achieved by direct, intratumoral injection of liposome-pDNA complexes, with only minimal expression in the surrounding normal liver. Therefore, direct liposome-pDNA complex injection appears far superior to systemic or portal intravenous administration for gene therapy of localized intrahepatic tumors, and may be a useful adjunct in the treatment of human HCCs. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Mol Hepatol Lab, Charlestown, MA 02129 USA. Univ Hosp, Dept Med 2, D-79106 Freiburg, Germany. Genzyme Corp, Framingham, MA 01701 USA. Rhode Isl Hosp, Liver Res Ctr, Providence, RI 02903 USA. RP Mohr, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Mol Hepatol Lab, Charlestown, MA 02129 USA. OI Scaglioni, Pier Paolo/0000-0002-6036-5138 FU NCI NIH HHS [CA35711]; NIAAA NIH HHS [AA-08169] NR 55 TC 40 Z9 44 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 2001 VL 12 IS 7 BP 799 EP 809 DI 10.1089/104303401750148748 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 428YB UT WOS:000168488300006 PM 11339896 ER PT J AU Hoffman, MA Ohh, M Yang, HF Klco, JM Ivan, M Kaelin, WG AF Hoffman, MA Ohh, M Yang, HF Klco, JM Ivan, M Kaelin, WG TI von Hippel-Lindau protein mutants linked to type 2C VHL disease preserve the ability to downregulate HIF SO HUMAN MOLECULAR GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; RENAL-CARCINOMA CELLS; CENTRAL-NERVOUS-SYSTEM; GERMLINE MUTATIONS; FACTOR-ALPHA; CAPILLARY HEMANGIOBLASTOMA; FAMILIAL PHEOCHROMOCYTOMA; FACTOR RECEPTOR; MESSENGER-RNAS AB von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by germ line mutation of the von Hippel-Lindau tumor suppressor gene(VHL). Tumors observed in this disorder include retinal and central nervous system hemangioblastomas, clear cell renal carcinomas and pheochromocytomas, The VHL gene product, pVHL, is a component of a ubiquitin ligase which targets the transcription factor known as hypoxia-inducible factor (HIF) for degradation in the presence of oxygen. pVHL also plays roles in the control of extracellular matrix formation and cell-cycle exit. Different VHL mutations confer different site-specific risks of cancer, Type 2C VHL mutations confer an increased risk of pheochromocytoma without the other stigmata of VHL disease. Here we report that the products of such type 2C VHL alleles retain the ability to down regulate HIF but are defective for promotion of fibronectin matrix assembly. Furthermore, pVHL L188V, a well studied type 2C mutant, retained the ability to suppress renal carcinoma growth in vivo. These studies strengthen the notion that HIF deregulation plays a causal role in hemangioblastoma and renal carcinoma, and raises the possibility that abnormal fibronectin matrix assembly contributes to pheochromocytoma pathogenesis in the setting of VHL disease. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. RI Ivan, Mircea/A-8109-2012; OI Klco, Jeffery/0000-0003-2961-6960 NR 62 TC 252 Z9 258 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2001 VL 10 IS 10 BP 1019 EP 1027 DI 10.1093/hmg/10.10.1019 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 433RN UT WOS:000168773700002 PM 11331612 ER PT J AU Cariappa, A Tang, M Parng, C Nebelitskiy, E Carroll, M Georgopoulos, K Pillai, S AF Cariappa, A Tang, M Parng, C Nebelitskiy, E Carroll, M Georgopoulos, K Pillai, S TI The follicular versus marginal zone B lymphocyte cell fate decision is regulated by Aiolos, Btk, and CD21 SO IMMUNITY LA English DT Article ID POSITIVE SELECTION; ANTI-IG; MICE; RECEPTOR; EXPRESSION; IMMUNOGLOBULIN; ACTIVATION; PROTEIN; SPLEEN; MOUSE AB Most splenic B cells in mice that lack Aiolos are mature IgD(hi)IgM(lo) follicular lymphocytes, suggesting that maturation signals delivered via the BCR are enhanced in the absence of Aiolos. The enhanced maturation of follicular B cells is accompanied by the absence of MZ B lymphocytes and the downregulation of CD21 expression in follicular B cells, all of which depend on the generation of signals via Btk, which is in epistasis to Aiolos. The inverse relationship between the strength of BCR signaling and MZ B cell development is supported by an examination of MZ B cells in CD21 null mice. These data support the view that antigens tin contrast to "tonic" signals) drive the development of naive B cells. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. FU NCI NIH HHS [CA69618]; NIAID NIH HHS [AI33507, AI42254] NR 43 TC 223 Z9 225 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2001 VL 14 IS 5 BP 603 EP 615 DI 10.1016/S1074-7613(01)00135-2 PG 13 WC Immunology SC Immunology GA 435KP UT WOS:000168880900012 PM 11371362 ER PT J AU Chen, T Nakayama, K Belliveau, L Duncan, MJ AF Chen, T Nakayama, K Belliveau, L Duncan, MJ TI Porphyromonas gingivalis gingipains and adhesion to epithelial cells SO INFECTION AND IMMUNITY LA English DT Article ID PROTEINASE ARG-GINGIPAIN; CYSTEINE PROTEINASE; STRUCTURAL CHARACTERIZATION; MOLECULAR-CLONING; MATRIX PROTEINS; PROTEASE; FIMBRIAE; BINDING; COMPLEXES; VIRULENCE AB Porphyromonas gingivalis is one of the principal organisms associated with adult periodontitis, Bacterial surface proteins such as fimbriae and gingipain hemagglutinin domains have been implicated as adhesins that actuate colonization of epithelium lining the gingival sulcus, We investigated the genetics of P, gingivalis adhesion to monolayers of epithelial cells using wild-type and gingipain mutant strains. These experiments suggested that arginine-specific gingipain (Rgp) catalytic activity modulated adhesion. From the data obtained with rgp mutants, we constructed a working hypothesis predicting that attachment and detachment of P. gingivalis to epithelial cells were mediated by gingipain adhesin and Rgp catalytic domains, respectively. A membrane-based epithelial cell binding assay used to locate adhesins in extracellular fractions of wild type and mutant strains, recognized gingipain peptides as adhesins rather than fimbriae. We developed a capture assay that demonstrated the binding of gingipain adhesin peptides to oral epithelial cells. The adherence of fimbrillin to epithelial cells was detected after heat denaturation of fell fractions. The prediction that Rgp catalytic activities mediated detachment was substantiated when the high level of attachment of an rgp mutant was reduced in the presence of wild-type cell fractions that contained gingipain catalytic activities. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Nagasaki Univ, Fac Dent, Dept Microbiol, Nagasaki 852, Japan. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [R01 DE10510, R01 DE010510] NR 42 TC 85 Z9 92 U1 0 U2 3 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 MAY PY 2001 VL 69 IS 5 BP 3048 EP 3056 DI 10.1128/IAI.69.5.3048-3056.2001 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 423CT UT WOS:000168158400036 PM 11292723 ER PT J AU Smith, DJ King, WF Godiska, R AF Smith, DJ King, WF Godiska, R TI Passive transfer of immunoglobulin Y antibody to Streptococcus mutans glucan binding protein B can confer protection against experimental dental caries SO INFECTION AND IMMUNITY LA English DT Article ID EGG-YOLK; MONOCLONAL-ANTIBODIES; SEQUENCE-ANALYSIS; IMMUNIZATION; SOBRINUS; GLUCOSYLTRANSFERASE; GENE; PLAQUE; RATS; IMMUNOTHERAPY AB Active immunization with Streptococcus mutans glucan binding protein B (GBP-B) lias been shown to induce protection against experimental dental caries. This protection presumably results from continuous secretion of salivary antibody to GBP-B, which inhibits accumulation of S, mutans within the oral biofilm. The purpose of this st;dy was to explore the influence of short-term (9- or 24-day) passive oral administration of antibody to S, mutans GBP-B on the longer term accumulation and cariogenicity of S, mutans in a rat model of dental caries. Preimmune chicken egg yolk immunoglobulin Y (IgY) or IgY antibody to S. mutans GBP-B was supplied in loner (experiment I) and higher (experiment 2) concentrations in the diet and drinking water of rats for 9 (experiment 1) or 24 (experiment) days. During the first 3 days of IgY feeding, all animals were challenged with 5 x 10(6) streptomycin-resistant S, mutans strain SJ-r organisms. Rats remained infected with S, mutans for 78 days, during which rat molars were sampled far the accumulation of S, mutans SJ-r bacteria and total streptococci. Geometric mean levels of S, mutans SJ-r accumulation on molar surfaces were significantly lower in antibody-treated rats on days 16 and 78 of experiment 2 and were lower on all but the initial (day 5) swabbing occasions in both experiments. Relative to controls, the extent of molar dental caries measured on day 78 was also significantly decreased. The decrease in molar caries correlated with the amount and duration of antibody administration. This is the first demonstration that passive antibody to S, mutans GBP-B can have a protective effect against cariogenic S. mutans infection and disease. Furthermore, this decrease in infection and disease did not require continuous antibody administration for the duration of the infection period. This study also indicates that antibody to components putatively involved only in cellular aggregation can have a significant effect on the incorporation of mutans streptococci in dental biofilm. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Ophidian Pharmaceut Inc, Madison, WI 53711 USA. RP Smith, DJ (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. OI Godiska, Ronald/0000-0003-0101-6365 FU NIDCR NIH HHS [DE-06153, R37 DE006153] NR 32 TC 50 Z9 62 U1 0 U2 3 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 MAY PY 2001 VL 69 IS 5 BP 3135 EP 3142 DI 10.1128/IAI.69.5.3135-3142.2001 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 423CT UT WOS:000168158400046 PM 11292733 ER PT J AU Venkatesan, MM Goldberg, MB Rose, DJ Grotbeck, EJ Burland, V Blattner, FR AF Venkatesan, MM Goldberg, MB Rose, DJ Grotbeck, EJ Burland, V Blattner, FR TI Complete DNA sequence and analysis of the large virulence plasmid of Shigella flexneri SO INFECTION AND IMMUNITY LA English DT Article ID ENTEROINVASIVE ESCHERICHIA-COLI; COMPLETE GENOME SEQUENCE; GROUP-II INTRON; PATHOGENICITY ISLAND; INCFII PLASMID-NR1; BASIC REPLICON; ANTIGEN GENES; IN-VITRO; EVOLUTION; PROTEINS AB The complete sequence analysis of the 210-kb Shigella flexneri 5a virulence plasmid was determined. Shigella spp. cause dysentery and diarrhea by invasion and spread through the colonic mucosa. Most of the known Shigella virulence determinants are encoded on a large plasmid that is unique to virulent strains of shigella and enteroinvasive Escherichia coli; these known genes account for approximately 30 to 35% of the virulence plasmid. In the complete sequence of the virulence plasmid, 286 open reading frames (ORFs) were identified. An astonishing 153 (53%) of these were related to known and putative insertion sequence (IS) elements; no known bacterial plasmid has previously been described with such a high proportion of IS elements. Pour new IS elements were identified. Fifty putative proteins show no significant homology to proteins of known function; of these, 18 have a G+C content of less than 40%, typical of known virulence genes on the plasmid. These 18 constitute potentially unknown virulence genes, Two alleles of shet2 and five alleles of ipaH were also identified on the plasmid, Thus, the plasmid sequence suggests a remarkable history of IS mediated acquisition of DNA across bacterial species. The complete sequence sill permit targeted characterization of potential new Shigella virulence determinants. C1 Walter Reed Army Inst Res, Dept Enter Infect, Div Communicable Dis & Immunol, Silver Spring, MD 20910 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. RP Venkatesan, MM (reprint author), Walter Reed Army Inst Res, Dept Enter Infect, Div Communicable Dis & Immunol, 503 Robert Forney Dr, Silver Spring, MD 20910 USA. EM Malabi.Venkatesan@NA.AMEDD.ARMY.MIL; mgoldberg1@partners.org FU NIAID NIH HHS [AI43562] NR 75 TC 122 Z9 182 U1 1 U2 10 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 MAY PY 2001 VL 69 IS 5 BP 3271 EP 3285 DI 10.1128/IAI.69.5.3271-3285.2001 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 423CT UT WOS:000168158400063 PM 11292750 ER PT J AU Sands, BE Tremaine, WJ Sandborn, WJ Rutgeerts, PJ Hanauer, SB Mayer, L Targan, SR Podolsky, DK AF Sands, BE Tremaine, WJ Sandborn, WJ Rutgeerts, PJ Hanauer, SB Mayer, L Targan, SR Podolsky, DK TI Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: A pilot study SO INFLAMMATORY BOWEL DISEASES LA English DT Article DE infliximab; monoclonal antibody; steroid-refractory; tumor necrosis factor alpha; ulcerative colitis ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY BOWEL-DISEASE; MONOCLONAL-ANTIBODY CA2; CROHNS-DISEASE; FACTOR-ALPHA; INTESTINAL BIOPSIES; TNF-ALPHA; CYCLOSPORINE; CYTOKINES; THERAPY AB We report the experience of 11 patients (of 60 planned patients) enrolled in a double-blind, placebo-controlled clinical trial of infliximab in patients with severe, active steroid-refractory ulcerative colitis. The study was terminated prematurely because of slow enrollment. Patients having active disease for at least 2 weeks and receiving at least 5 days of intravenous corticosteroids were eligible to receive a single intravenous infusion of infliximab at 5, 10, or 20 mg/kg body weight. The primary endpoint used in this study was treatment failure at 2 weeks after infusion. Treatment failure was defined as 1) unachieved clinical response as defined by a modified Truelove and Witts severity score, 2) increase in corticosteroid dosage, 3) addition of immunosuppressants, 4) colectomy, or 5) death. Safety evaluations included physical examination, clinical chemistry and hematology laboratory tests, and occurrence of adverse experiences. Four of 8 patients (50%) who received infliximab were considered treatment successes at 2 weeks. compared with none of 3 patients who received placebo. Improvement in erythrocyte sedimentation rates and serum concentrations of C-reactive protein and interleukin-6 correlated with the clinical response observed in patients receiving infliximab. Infusion with infliximab produced no significant adverse events. Infliximab was well tolerated and may provide clinical benefit fur some patients with steroid-refractory ulcerative colitis. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Univ Chicago, Chicago, IL 60637 USA. Mt Sinai Hosp, New York, NY 10029 USA. Cedars Sinai Hosp, Los Angeles, CA USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,GRJ 825, Boston, MA 02114 USA. FU NIDDK NIH HHS [1 K23 DK02850-01K23] NR 22 TC 261 Z9 279 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 2001 VL 7 IS 2 BP 83 EP 88 DI 10.1097/00054725-200105000-00001 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 430GV UT WOS:000168566900001 PM 11383595 ER PT J AU Zietman, A Moughan, J Owen, J Hanks, G AF Zietman, A Moughan, J Owen, J Hanks, G TI The patterns of care survey of radiation therapy in localized prostate cancer: Similarities between the practice nationally and in minority-rich areas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; radiation therapy; racial minorities ID RADICAL PROSTATECTOMY; DOSE-ESCALATION; ANTIGEN VALUES; ONCOLOGY GROUP; MEDICAL-CARE; BLACK; ACCESS; RACE; SURVIVAL AB Purpose: Over the last two decades, the chance for the cure of localized prostate cancer by radiation has been improved by the widespread use of PSA for early detection and by a number of technical advances in treatment delivery. This study was designed to determine whether the stage of presentation and the quality of radiation treatment delivered are comparable between Caucasian and minority patients nationally and within minority-rich areas. Methods and Materials: A random survey conducted for the Patterns of Care Study in Radiation Oncology of 80 facilities treating patients with radiation in the USA. Of these, 67 comprise the "National Survey" and 13 a "Minority-Rich" survey (>40% of treated patients are minorities). Nine hundred twenty-six men with localized prostate cancer were treated in 1994, Five hundred ninety-five were in the national and 331 in the minority-rich survey. The main outcome measures were the clinical features of Caucasian and minority men at presentation and technical characteristics of the treatment delivered to them. Results: African-American men presented with more advanced disease (higher-presenting PSA and T-stage) than Caucasians in both the national and the minority-rich surveys. Hispanics also presented with later disease and could be grouped with African-American men rather than Caucasians, Overall the stage and PSA at presentation was earlier than seen in the previous Patterns of Care Study survey of 1989, The quality of treatment delivered has improved since 1989, with no distinction seen between those facilities sampled nationally and those within minority-rich areas. Conclusion: African-American and Hispanic men with prostate cancer present for therapy at a later stage than Caucasian men, but when they do, the treatment received is of comparable quality. (C) 2001 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Amer Coll Radiol, Philadelphia, PA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Zietman, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [CA 65435] NR 18 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2001 VL 50 IS 1 BP 75 EP 80 DI 10.1016/S0360-3016(00)01569-8 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 425XD UT WOS:000168316200010 PM 11316549 ER PT J AU Gieschen, HL Spiro, IJ Suit, HD Ott, MJ Rattner, DW Ancukiewicz, M Willett, CG AF Gieschen, HL Spiro, IJ Suit, HD Ott, MJ Rattner, DW Ancukiewicz, M Willett, CG TI Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE retroperitoneal sarcoma; radiation therapy; intraoperative radiation therapy ID RADIATION-THERAPY; MANAGEMENT AB Purpose: This study assesses the long-term outcome of patients with retroperitoneal sarcoma treated by preoperative external beam radiotherapy, resection, and intraoperative electron beam radiation (IOERT), Methods and Materials: From 1980 to 1996, 37 patients were treated with curative intent for primary or recurrent retroperitoneal soft tissue sarcoma, All patients underwent external beam radiotherapy with a median dose of 45 Gy, This was followed by laparotomy, resection, and IOERT, if feasible. Twenty patients received 10-20 Gy of IOERT with 9-15 MeV electrons. These patients were compared to a group of 17 patients receiving preoperative irradiation without IOERT, Results: The 5-yr actuarial overall survival (OS), disease-free survival, local control (LC), and freedom from distant disease of all 37 patients was 50%, 38%, 59%, and 54%, respectively, After preoperative irradiation, 29 patients (78%) underwent gross total resection, For 16 patients undergoing gross total resection and IOERT, OS and LC were 74% and 83%, respectively. In contrast, these results were less satisfactory for 13 patients undergoing gross total resection without IOERT, For these patients, OS and LC were 30% and 61%, respectively. Four patients experienced treatment-related morbidity, Conclusions: In selected patients, IOERT results in excellent local control and disease-free survival with acceptable morbidity, (C) 2001 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA 02114 USA. Cape Cod Hosp, Reg Canc Ctr, Hyannis, MA USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 11 TC 100 Z9 109 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 MAY 1 PY 2001 VL 50 IS 1 BP 127 EP 131 DI 10.1016/S0360-3016(00)01589-3 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 425XD UT WOS:000168316200016 PM 11316555 ER PT J AU Russo, SM Tepper, JE Baldwin, AS Liu, R Adams, J Elliott, P Cusack, JC AF Russo, SM Tepper, JE Baldwin, AS Liu, R Adams, J Elliott, P Cusack, JC TI Enhancement of radiosensitivity by proteasome inhibition: Implications for a role of NF-kappa B SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiation; apoptosis; NF-kappa B; I kappa B; proteasome inhibitor PS-341 ID IMMEDIATE-EARLY GENES; CANCER-THERAPY; TRANSCRIPTION; RADIATION; INDUCTION; PS-341; ACTIVATION; APOPTOSIS; AGENT; CELLS AB Purpose: NF-kappaB is activated by tumor necrosis factor, certain chemotherapeutic agents, and ionizing radiation, leading to inhibition of apoptosis, NF-kappaB activation is regulated by phosphorylation of I kappaB inhibitor molecules that are subsequently targeted for degradation by the ubiquitin-proteasome pathway. PS-341 is a specific and selective inhibitor of the proteasome that inhibits NF-kappaB activation and enhances cytotoxic effects of chemotherapy in vitro and in vivo, The objective of this study was to determine if proteasome inhibition leads to enhanced radiation sensitivity. Methods and Materials: Inhibition of NF-kappaB activation in colorectal cancer cells was performed by treatment of LOVO cells with PS-341 or infection with an adenovirus encoding I kappaB super-repressor, a selective NF-kappaB inhibitor. Cells were irradiated at 0, 2, 4, 6, 8, and 10 Gy with or without inhibition of NF-kappaB, NF-kappaB activation was determined by electrophoretic mobility gel shift assay, and apoptosis was evaluated using the TUNEL assay, Growth and clonogenic survival data were obtained to assess effects of treatment on radiosensitization, In vitro results were tested in vivo using a LOVO xenograft model, Results: NF-kappaB activation was induced by radiation and inhibited by pretreatment with either PS-341 or I kappaB alpha super-repressor in all cell lines. Inhibition of radiation-induced NF-kappaB activation resulted in increased apoptosis and decreased cell growth and clonogenic survival, A 7-41% increase in radiosensitivity was observed for cells treated with PS-341 or I kappaB alpha, An 84% reduction in initial tumor volume was obtained in LOVO xenografts receiving radiation and PS-341, Conclusions: Inhibition of NF-kappaB activation increases radiation-induced apoptosis and enhances radiosensitivity in colorectal cancer cells in vitro and in vivo. Results are encouraging for the use of PS-341 as a radiosensitizing agent in the treatment of colorectal cancer. (C) 2001 Elsevier Science Inc. C1 Univ N Carolina, Sch Med, Dept Radiat Oncol, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Surg, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. Millennium Pharmaceut, Cambridge, MA USA. RP Cusack, JC (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Cox 626,100 Blossom St, Boston, MA 02114 USA. NR 30 TC 263 Z9 277 U1 0 U2 5 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 MAY 1 PY 2001 VL 50 IS 1 BP 183 EP 193 DI 10.1016/S0360-3016(01)01446-8 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 425XD UT WOS:000168316200024 PM 11316563 ER PT J AU Wyss, C Dewhirst, FE Gmur, R Thurnheer, T Xue, Y Schupbach, P Guggenheim, B Paster, BJ AF Wyss, C Dewhirst, FE Gmur, R Thurnheer, T Xue, Y Schupbach, P Guggenheim, B Paster, BJ TI Treponema parvum sp nov., a small, glucuronic or galacturonic acid-dependent oral spirochaete from lesions of human periodontitis and acute necrotizing ulcerative gingivitis SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article DE Treponema; oral spirochaetes; periodontitis; ANUG; glucuronidase ID SACCHAROLYTIC SPIROCHETE; OUTER-MEMBRANE; PECTINOVORUM; DIVERSITY; PHYLOGENY; DENTICOLA; TISSUE; PLAQUE; GROWTH; FLORA AB Small oral spirochaetes with a strict dependence on either glucuronic acid (GluA) or galacturonic acid (GalA) were isolated from European patients with periodontitis and from Chinese patients with either gingivitis or acute necrotizing ulcerative gingivitis (ANUG). Thirteen such isolates were similar phenotypically to Treponema pectinovorum ATCC 33768(T) and this classification was confirmed by 16S rRNA sequencing. However, four isolates differed from T. pectinovorum by their small cell size, by a prominent beta -glucuronidase activity, by a distinct protein and antigen profile, by an inability to grow on pectin as sole source of carbohydrate and by a markedly enhanced growth rate when supplied with a second carbohydrate (L-arabinose, D-galactose, D-glucose, D-fructose, D-mannitol, D-mannose, pectin, D-ribose or D-xylose) in addition to the essential GluA/GalA. By 16S rRNA sequencing these four isolates clustered in the recently described phylotype 'Smibert-2'. T. pectinovorum (14 strains) and 'Smibert-2' (four isolates with beta -glucuronidase activity) could each be subdivided into two serotypes based on immunoblot reactivity with two mAbs. Representatives of the two groups, including T. pectinovorum ATCC 33768T, showed a 1:2:1-type periplasmic flagellar arrangement. 'Smibert-2' is described as a novel species, Treponema parvum sp, nov., with isolate OMZ 833(T) (= ATCC 700770(T)) proposed as the type strain and OMZ 842 (= ATCC 700773) as reference strain for a second serotype. C1 Univ Zurich, Inst Orale Mikrobiol & Allgemeine Immunol, Zentrum Zahn Mund & Kieferheilkunde, CH-8028 Zurich, Switzerland. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Wyss, C (reprint author), Univ Zurich, Inst Orale Mikrobiol & Allgemeine Immunol, Zentrum Zahn Mund & Kieferheilkunde, Plattenstr 11, CH-8028 Zurich, Switzerland. FU NIDCR NIH HHS [DE-10374, DE-11443] NR 32 TC 26 Z9 27 U1 0 U2 7 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD MAY PY 2001 VL 51 BP 955 EP 962 PN 3 PG 8 WC Microbiology SC Microbiology GA 435UP UT WOS:000168900000028 PM 11411720 ER PT J AU Woody, GE VanEtten-Lee, ML McKirnan, D Donnell, D Metzger, D Seage, G Gross, M AF Woody, GE VanEtten-Lee, ML McKirnan, D Donnell, D Metzger, D Seage, G Gross, M CA HIVNET VPS 001 Protocol Team TI Substance use among men who have sex with men: Comparison with a national household survey SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE substance use; MSM ID HOMOSEXUAL MEN; DRUG-USE; RISK BEHAVIOR; NITRITE INHALANTS; HIV-INFECTION; GAY MEN; AIDS; ALCOHOL; SEROCONVERSION; EPIDEMIOLOGY AB Objective: Compare substance use among men who have sex with men (MSM) at high risk for HIV infection to a nationally representative sample of heterosexual men. Methods: Compare data from surveys of 3,212 MSM recruited for participation in a Vaccine Preparedness Study (VPS) with an age-standardized group of 2481 single, urban-dwelling men from the 1995 National Household Survey on Drug Abuse (NHSDA). Results: Except for alcohol, relative risk (RR [95% confidence interval (CI)I) for use of any substance was higher in the VPS than the National Household Survey on Drug Abuse (NHSDA) (3.64 [3.01-4.42]). Drugs with the highest relative risks were "poppers" (21.6 [15.2-30.8]), sedatives (6.98 [2.46-19.8]), hallucinogens (6.14 [4.61-8.17]), tranquilizers (4.99 [2.96-8.42]), and stimulants (4.47 [3.58-5.58]), RR was higher for weekly use of poppers (33.5 [12.5-89.6]), stimulants (2.75 [1.79-4.22]), marijuana (2.37 [1.93-2.92]), and cocaine (2.24 [1.32-3.79]); and for daily use of marijuana (1.49 [1.08-2.05]). Conclusions: Participants in the VPS used more substances than a group of age-standardized, single, urban-dwelling men from the NHSDA. In view of previous data showing that substance use can be associated with unprotected sex, assessing substance use among MSM at high risk for HIV infection is an important component of risk reduction efforts. C1 Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Chicago, Chicago, IL 60637 USA. Howard Brown Hlth Ctr, Chicago, IL USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. ABT Associates Inc, Cambridge, MA 02138 USA. ABT Associates Inc, Bethesda, MD USA. Univ Washington, Seattle, WA 98195 USA. Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Sacramento, CA 95814 USA. Denver Hlth & Hosp, Denver, CO USA. Fenway Community Hlth Ctr, Boston, MA USA. New York Blood Ctr, New York, NY 10021 USA. NYU, Med Ctr, New York, NY 10016 USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Penn, Philadelphia, PA 19104 USA. RP Woody, GE (reprint author), Treatment Res Inst, 600 Publ Ledger Bldg,1500 Independence Mall W, Philadelphia, PA 19106 USA. RI Metzger, David/D-9499-2012; OI Donnell, Deborah/0000-0002-0587-7480 FU NCRR NIH HHS [MO1RR00096]; NIAID NIH HHS [AI27742, N01-AI-35176, N01-AI-45200]; NIDA NIH HHS [5T32DA07292, DA05593, P50DA05186, T32 DA07292] NR 20 TC 38 Z9 38 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD MAY 1 PY 2001 VL 27 IS 1 BP 86 EP 90 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 442YJ UT WOS:000169312300013 PM 11404525 ER PT J AU Wozniak, J Biederman, J Faraone, SV Blier, H Monuteaux, MC AF Wozniak, J Biederman, J Faraone, SV Blier, H Monuteaux, MC TI Heterogeneity of childhood conduct disorder: further evidence of a subtype of conduct disorder linked to bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE mania; bipolar disorder; conduct disorder; comorbidity; children ID DEFICIT HYPERACTIVITY DISORDER; LA-TOURETTES SYNDROME; GENETIC-RELATIONSHIP; AGGRESSIVE-CHILDREN; MULTIPLE THRESHOLDS; JUVENILE MANIA; RELIABILITY; COMORBIDITY; ADOLESCENTS; INTERVIEW AB Background: Although a small literature suggests that conduct disorder (CD) co-occurs with bipolar disorder (BPD), little is known about this overlap. Thus, we investigated the familial association of antisocial disorders (CD and/or antisocial personality disorder (ASPD)) and BPD among the first degree relatives of children with CD with and without comorbid BPD. Methods: We compared relatives of four proband groups defined by the presence or absence of CD and BPD in the proband: (1) CD + BPD (N = 26 probands, 92 relatives; (2) BPD without CD (BPD) (N = 19 probands, 53 relatives); (3) CD without BPD (CD) (N = 16 probands, 58 relatives); and (4) controls without BPD or CD (N = 102 probands, 338 relatives). All subjects were evaluated with structured diagnostic interviews. Diagnoses of relatives were made blind to the diagnoses of probands. Results: The results show high rates of antisocial disorders and BPD in relatives of children with CD + BPD. Moreover, antisocial disorders and BPD cosegregated among the relatives of children with CD + BPD. While relatives of both CD proband groups with and without BPD had high rates of CD/ASPD, the combined condition CD/ASPD + BPD was found exclusively among relatives of probands with CD + BPD. Limitations: Since we pooled two datasets, subjects were not all evaluated;It the same time. Also, the lack of direct psychiatric interviews with children younger than 12 may have decreased the sensitivity of some diagnoses. Conclusions: These family-genetic findings suggest that CD and BPD represent separate disorders. Furthermore, they suggest that the comorbid condition of CD + BPD may be a distinct nosological entity. This suggests that clinicians treating CD or BPD children should consider the treatment implications of this comorbid condition. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Child Psychiat Serv, Boston, MA USA. RP Wozniak, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH50657*05] NR 41 TC 36 Z9 37 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 2001 VL 64 IS 2-3 BP 121 EP 131 DI 10.1016/S0165-0327(00)00217-2 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 431DC UT WOS:000168604400002 PM 11313079 ER PT J AU Shipherd, JC Beck, JG Ohtake, PJ AF Shipherd, JC Beck, JG Ohtake, PJ TI Relationships between the anxiety sensitivity index, the suffocation fear scale, and responses to CO2 inhalation SO JOURNAL OF ANXIETY DISORDERS LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Advancement-of-Behavior-Therapy CY NOV 05-08, 1998 CL WASHINGTON, D.C. SP Assoc Adv Beh Therapy DE anxiety sensitivity index; panic disorder; suffocation fear scare; respiratory challenge ID CARBON-DIOXIDE CHALLENGE; BREATH-HOLDING DURATION; PANIC DISORDER; TRAIT ANXIETY; ENRICHED AIR; HYPERVENTILATION; CLAUSTROPHOBIA; PREDICTORS; REDUCTION AB Interest in documenting ways to predict anxious responding in panic disorder (PD) patients has proliferated recently in the literature. In the current study, two self-report measures were assessed to determine their relative utility in predicting responses to a panicogenic challenge. The Anxiety Sensitivity Index (ASI) and the Suffocation Fear Scale (SFS) were evaluated by correlating scores on these measures with reactions to inhalation of 35% carbon dioxide (CO2), assessed via anxiety ratings, panic symptom intensity, tidal volume (V-T) and respiratory rate (RR). A sample of 14 PD patients and 14 matched control (MC) participants demonstrated that the relationship between ASI scores and responses to 35% CO2 were stronger than the relationship between SFS scores and responses to CO2. Specifically, both respiratory responses (V-T and RR) and self-reported reactions (anxiety and symptom intensity) were significantly correlated with scores on the ASI, In contrast, scores on the SFS were significantly correlated with only one measure of respiratory change (V-T). Although preliminary, these data indicate that the ASI may be a more useful tool than the SFS in predicting self-reported and respiratory responses to CO2 challenges. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Boston VA Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. SUNY Buffalo, Dept Phys Therapy Exercise & Nutr Sci, Buffalo, NY 14260 USA. RP Shipherd, JC (reprint author), Boston VA Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA. NR 35 TC 17 Z9 17 U1 5 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAY-JUN PY 2001 VL 15 IS 3 BP 247 EP 258 DI 10.1016/S0887-6185(00)00050-5 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 443KR UT WOS:000169340800008 PM 11442142 ER PT J AU Wucherpfennig, KW AF Wucherpfennig, KW TI Structural basis of molecular mimicry SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT International Symposium on Autoimmunity Induced by Infection or Immunization CY NOV 28-DEC 01, 2000 CL LES PENSIERES, FRANCE SP Merieux Fdn ID T-CELL CLONES; MHC CLASS-II; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MULTIPLE-SCLEROSIS PATIENTS; CRYSTAL-STRUCTURE; PROTEIN PEPTIDE; RELAPSING PARALYSIS; ANTIGENIC PEPTIDE; SELF-PEPTIDES AB Infectious agents are thought to play an important role in the development of autoimmune diseases. Sequence similarity between infectious agents and self-proteins (molecular mimicry) has been proposed as a mechanism for the induction of autoimmunity [1]. However, it has been difficult to identify microbial peptides that activate autoreactive T cells using conventional sequence alignments. This chapter reviews progress made in the identification of such microbial peptides based on the analysis of structural features that are important for TCR recognition of MHC-bound peptides [2]. (C) 2001 Academic Press. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Room D1410, Boston, MA 02115 USA. FU NINDS NIH HHS [R01 NS39096] NR 58 TC 64 Z9 67 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD MAY PY 2001 VL 16 IS 3 SI SI BP 293 EP 302 DI 10.1006/jaut.2000.0499 PG 10 WC Immunology SC Immunology GA 431XG UT WOS:000168656600016 PM 11334495 ER PT J AU Panoutsakopoulou, V Cantor, H AF Panoutsakopoulou, V Cantor, H TI On the relationship between viral infection and autoimmunity SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT International Symposium on Autoimmunity Induced by Infection or Immunization CY NOV 28-DEC 01, 2000 CL LES PENSIERES, FRANCE SP Merieux Fdn ID CENTRAL-NERVOUS-SYSTEM; THEILERS MURINE ENCEPHALOMYELITIS; T-CELL RESPONSES; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; (TMEV)-INDUCED DEMYELINATING DISEASE; HERPES STROMAL KERATITIS; SIMPLEX VIRUS TYPE-1; DIABETIC NOD MICE; TRANSGENIC MICE C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, SM 722,44 Binney St, Boston, MA 02115 USA. OI Panoutsakopoulou, Vily/0000-0002-1569-1508 FU NIAID NIH HHS [AI48125, AI12184, AI37562] NR 63 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD MAY PY 2001 VL 16 IS 3 SI SI BP 341 EP 345 DI 10.1006/jaut.2000.0480 PG 5 WC Immunology SC Immunology GA 431XG UT WOS:000168656600023 PM 11334502 ER PT J AU Mankin, HJ Rosenthal, DI Xavier, R AF Mankin, HJ Rosenthal, DI Xavier, R TI Gaucher disease - New approaches to an ancient disease SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID ENZYME REPLACEMENT THERAPY; MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; BONE-MARROW; SKELETAL COMPLICATIONS; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; MEDIATED TRANSFER; INVOLVEMENT; PATIENT; RESPONSES C1 Massachusetts Gen Hosp, Orthopaed Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Serv, Boston, MA 02114 USA. NR 98 TC 25 Z9 30 U1 0 U2 0 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 MAY PY 2001 VL 83A IS 5 BP 748 EP 762 PG 15 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 433KD UT WOS:000168757800016 PM 11379747 ER PT J AU Choi, SJ Han, JH Roodman, GD AF Choi, SJ Han, JH Roodman, GD TI ADAM8: A novel osteoclast stimulating factor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE ADAM8; macrophage colony-stimulating factor; polymerase chain reaction; osteoclasts ID LARGE T-ANTIGEN; BCL-X-L; BONE-RESORPTION; METALLOPROTEASE DOMAIN; MEMBRANE-PROTEINS; DISINTEGRIN; FAMILY; CELL; GENE; IDENTIFICATION AB We used polymerase chain reaction (PCR)-selective complementary DNA (cDNA) subtraction hybridization with an immortalized murine osteoclast (OCL) precursor cell line to identify genes that are highly expressed in OCLs compared with OCL precursors and which map be involved in the OCL differentiation process. ADAM8 was one of the 50 genes identified. ADAM (a disintegrin and metalloproteinase) peptides are membrane-bound proteins that can act as cell-to-cell and cell-to-matrix adhesion molecules, degrade the extracellular matrix, and play a role in tissue morphogenesis, Addition of antisense (AS) S-oligonucleotides for ADAM8 (1-10 nM) to mouse bone marrow cultures treated with 10(-9) Ri 1,25-dihgdroxyvitamin D-3 [1,25(OH)(2)D-3] significantly inhibited OCL formation compared with treatment with the control S-oligonucleotide, Furthermore, conditioned media from 293 cells transiently transfected with a secretable form of the ADAM8 cDNA increased OCL formation in a dose-dependent manner. In addition, treatment of OCLs with soluble ADAM8 conditioned media significantly increased pit formation per dentin slice compared with control OCLs. Time course studies indicated that ADAM8 increased OCL formation only when it was present during days 4-7 of the 7-day culture period. Structural analysis, using truncated constructs of ADAM8, showed that the cysteine-rich/disintegrin domain was responsible for its OCL stimulatory activity, Western blot analysis confirmed that the soluble form of ADAM8 is present in normal marrow cultures, These data suggest that ADAM8 plays an important role in OCL formation and acts primarily at the later stages of OCL differentiation. C1 Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Hematol, San Antonio, TX USA. RP Roodman, GD (reprint author), Audie L Murphy Mem Vet Hosp, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI Han, J/G-4671-2010 NR 22 TC 76 Z9 79 U1 0 U2 3 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 MAY PY 2001 VL 16 IS 5 BP 814 EP 822 DI 10.1359/jbmr.2001.16.5.814 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 423WV UT WOS:000168201500003 PM 11341326 ER PT J AU Sheridan, R Shapiro, A Kay, D Petras, L Lydon, M AF Sheridan, R Shapiro, A Kay, D Petras, L Lydon, M TI Initial experience with a prototype staple detector SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Burn-Association CY MAR 14-17, 2000 CL LAS VEGAS, NEVADA SP Amer Burn Assoc AB Stainless steel staples can be overgrown by granulation tissue or skin grafts and become buried in tissue. Although they are generally asymptomatic, they can on rare occasion erode to the surface or complicate the radiographic evaluation of pain not related to the staples. A device to facilitate detection of retained staples would be desirable, but it has been difficult to develop because stainless steel staples have poor magnetic and conductive properties. A prototype device, based on the presence of metal disturbing a low-power electromagnetic field, was developed. With human studies committee approval, this miniaturized detector was used in 13 burn patients to detect staples during planned removal of large numbers of staples. Staples were first removed using visual inspection and palpation of the wounds. This was followed by use of the staple detector. The age of the patients was 10.8 +/- 3.3 years, and burn size was 54.6 +/- 8.8% of the body surface. In 8 (62%) of the patients one or more additional staples were detected by the device that would otherwise have been overlooked. In 4 (31%) of the patients there was a false-positive signal, possibly related to topical silver in the wounds, that required additional focused physical examination. A portable staple detector has been developed. Initial experience with the device is favorable and warrants an expanded trial, which is in the planning stages. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Nav Biomes, Boston, MA USA. RP Sheridan, R (reprint author), Shriners Burns Hosp, 51 Blosson St, Boston, MA 02114 USA. NR 1 TC 4 Z9 4 U1 0 U2 1 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 MAY-JUN PY 2001 VL 22 IS 3 BP 232 EP 234 DI 10.1097/00004630-200105000-00009 PG 3 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 606TP UT WOS:000178749800006 PM 11403246 ER PT J AU Hilgenberg, AD Logan, DL AF Hilgenberg, AD Logan, DL TI Results of aortic arch repair with hypothermic circulatory arrest and retrograde cerebral perfusion SO JOURNAL OF CARDIAC SURGERY LA English DT Article AB Background: Repair of aortic arch pathology is reliably performed with hypothermic circulatory arrest, but the best method of brain protection is controversial. Methods: We reviewed a consecutive series of 67 patients who had aortic arch repair with hypothermic circulatory arrest. Retrograde perfusion of arterial blood into the superior vena cava (SVC) during systemic arrest was used in 87%. Average age was 65 years. Acute dissection was present in 25%. Average circulatory arrest time was 37 minutes, and average temperature 17.7degrees C. Results: Hospital mortality was 1.5%. Strokes occurred in 4.5%. Temporary neurological dysfunction occurred in 16%. Multivariate logistic regression analysis showed that acute dissection was the only independent predictor of the combined risk of stroke and temporary neurological dysfunction (odds ratio 8.5). Duration of circulatory arrest and patient age were not risk factors for adverse neurological outcome. Conclusion: Continuous arterial perfusion of the SVC during hypothermic circulatory arrest provides excellent cerebral protection for aortic arch repair. Acute dissection is an independent risk factor for adverse neurological outcome. Arrest time is not a predictor of neurological dysfunction. C1 Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hilgenberg, AD (reprint author), Massachusetts Gen Hosp, Thorac Aort Ctr, Warren 735, Boston, MA 02114 USA. NR 19 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD MAY-JUN PY 2001 VL 16 IS 3 BP 246 EP 251 DI 10.1111/j.1540-8191.2001.tb00515.x PG 6 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA V3376 UT WOS:000186228400010 PM 11824671 ER PT J AU Fairfield, WP Finkelstein, JS Klibanski, A Grinspoon, SK AF Fairfield, WP Finkelstein, JS Klibanski, A Grinspoon, SK TI Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; BIOCHEMICAL MARKERS; ANOREXIA-NERVOSA; BONE METABOLISM; INFECTION; HIV; WOMEN; TESTOSTERONE; RESORPTION AB Multiple endocrine and metabolic consequences of human immunodeficiency virus (HN) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting. Prior studies have not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men. To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% IBW or weight loss > 10% from preillness baseline) to receive either testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance training (3 times/week) or no training in a 2 x 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur, and total body; lean body mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 us. 1.084 +/- 0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 us. 1.070 +/- 0.019 g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 us. - 0.07 +/- 0.23, P = 0.05) and total hip (- 0.65 +/- 0.11 us. +0.20 +/- 0.014, P < 0.0001). Total hip T scores were less than - 1.0 in 33% of men with AIDS wasting. Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD. Serum osteocalcin levels were lower(3.63 +/- 0.29 vs. 4.54 +/- 0.31 nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5 us. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting than in controls. Lumbar spine BMD, as assessed on regional total body dual energy x-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone os, placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0 vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men. Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [F32-DK-09218, R01-DK-49302, K24-DK02759] NR 27 TC 53 Z9 54 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2001 VL 86 IS 5 BP 2020 EP 2026 DI 10.1210/jc.86.5.2020 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432ZV UT WOS:000168731600032 PM 11344201 ER PT J AU Ohta, K Endo, T Haraguchi, K Hershman, JM Onaya, T AF Ohta, K Endo, T Haraguchi, K Hershman, JM Onaya, T TI Ligands for peroxisome proliferator-activated receptor gamma inhibit growth and induce apoptosis of human papillary thyroid carcinoma cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CANCER CELLS; IN-VITRO; C-MYC; EXPRESSION; DIFFERENTIATION; FIBROBLASTS; MANAGEMENT; LINES AB Ligands for peroxisome proliferator-activated receptor gamma (PPAR gamma) induce apoptosis and exert antiproliferative effects on several carcinoma cell lines. The present study investigates the expression of PPAR gamma and the possibility that agonists for PPAR gamma, also inhibit the growth of human thyroid carcinoma cells. We examined this hypothesis using six cell lines, designated BHP thyroid carcinoma cells, which originated from patients with papillary thyroid carcinoma. RT-PCR analysis revealed that the thyroid carcinoma cell lines BHP2-7, 7-13, 10-3, and 18-21 express PPAR gamma. More PPAR gamma was expressed in carcinoma than in adjacent normal thyroid tissue in three of six samples of human papillary carcinoma of the thyroid. PPAR gamma -positive thyroid carcinoma cells were treated with agonists of PPAR gamma, troglitazone, BRL 49653, and 15-deoxy-Delta 12,14-prostaglandin J2. Troglitazone (10 mu mol/L), BRL 49653 (10 mu mol/L), and 15-deoxy-Delta 12,14-prostaglandin J2 (1 mug/mL) decreased [(3)H]thymidine incorporation and reduced cell number, respectively, in BHP carcinoma cell lines that expressed PPAR gamma. Under low serum conditions, ligands for PPAR gamma induced condensation of the nucleus and fragmentation of chromatin into nucleosome ladders. These findings indicate that the death of thyroid carcinoma cells is a form of apoptosis. To investigate the molecular mechanism of the apoptosis, we assessed expression of the apoptosis-regulatory genes bcl-2, bar, and c-myc. Troglitazone significantly increased the expression of c-myc messenger RNA but had no effect on the expression of bcl-2 and bar in thyroid carcinoma cells. These results suggest that, at least in part, the induction of apoptosis in human papillary thyroid carcinoma cells may be due to an increase of c-myc. Troglitazone (500 mg/kg.day) significantly inhibited tumor growth and prevented distant metastasis of BHP18-21 tumors in nude mice in vivo. Taken together, these results suggest that PPAR gamma agonist inhibit cell growth of some types of human thyroid cancer. C1 Yamanashi Med Univ, Dept Internal Med 3, Yamanashi 4093898, Japan. W Los Angeles Vet Affairs Med Ctr, Endocrine Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. RP Onaya, T (reprint author), Yamanashi Med Univ, Dept Internal Med 3, 1110 Shimo Kato Tamaho, Yamanashi 4093898, Japan. EM onayat@res.yamanashi-med.ac.jp NR 23 TC 164 Z9 173 U1 0 U2 4 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 MAY PY 2001 VL 86 IS 5 BP 2170 EP 2177 DI 10.1210/jc.86.5.2170 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432ZV UT WOS:000168731600053 PM 11344222 ER PT J AU Kim, SH Warram, JH Krolewski, AS Doria, A AF Kim, SH Warram, JH Krolewski, AS Doria, A TI Mutation screening of the neurogenin-3 gene in autosomal dominant diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID ONSET; PANCREAS; MELLITUS; MODY AB We investigated whether genetic variability in neurogenin-3, a basic helix-loop-helix transcription factor that is expressed in the developing pancreas, contributes to the etiology of maturity-onset diabetes of the young or other forms of autosomal dominant diabetes. Ninety-one probands of families with autosomal dominant diabetes were screened for neurogenin-3 mutations by dideoxy fingerprinting. Three sequence differences were identified: a polymorphism not affecting the amino acid sequence (L75L), a CA insertion/deletion in intron 1 (-44ins/del), and a C to T transition causing a serine to phenylalanine substitution (S199F). None of these sequence differences were more frequent in the family probands than in 179 nondiabetic controls. In contrast, allele 199F was weakly, but significantly, associated with common type 2 diabetes (199F frequencies = 0.436 in 132 cases with type 2 diabetes us. 0.346 in the family probands and 0.346 in controls; P = 0.05). The relative risk of type 2 diabetes for 199F carriers was 1.7 (95% confidence interval, 1.04-2.7). We conclude that sequence differences in the neurogenin-3 gene do not play a major role in the development of autosomal dominant diabetes. Rather, they might contribute to common type 2 diabetes, although this finding must be replicated in other populations. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu FU NIDDK NIH HHS [DK-55523, DK-47475, DK-36836] NR 9 TC 9 Z9 10 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2001 VL 86 IS 5 BP 2320 EP 2322 DI 10.1210/jc.86.5.2320 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432ZV UT WOS:000168731600076 PM 11344245 ER PT J AU Imanishi, Y Hosokawa, Y Yoshimoto, K Schipani, E Mallya, S Papanikolaou, A Kifor, O Tokura, T Sablosky, M Ledgard, F Gronowicz, G Wang, TC Schmidt, EV Hall, C Brown, EM Bronson, R Arnold, A AF Imanishi, Y Hosokawa, Y Yoshimoto, K Schipani, E Mallya, S Papanikolaou, A Kifor, O Tokura, T Sablosky, M Ledgard, F Gronowicz, G Wang, TC Schmidt, EV Hall, C Brown, EM Bronson, R Arnold, A TI Primary hyperparathyroidism caused by parathyroid-targeted overexpression of cyclin D1 in transgenic mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FAMILIAL HYPOCALCIURIC HYPERCALCEMIA; NEONATAL SEVERE HYPERPARATHYROIDISM; CA2+-SENSING RECEPTOR GENE; CALCIUM-SENSING RECEPTOR; EXPRESSION; ADENOMAS; HORMONE; TISSUE; TUMORS; CELLS AB The relationship between abnormal cell proliferation and aberrant control of hormonal secretion is a fundamental and poorly understood issue in endocrine cell neoplasia. Transgenic mice with parathyroid-targeted overexpression of the cyclin D1 oncogene, modeling a gene rearrangement found in human tumors, were created to determine whether a primary defect in this cell-cycle regulator can cause an abnormal relationship between serum calcium and parathyroid hormone response, as is typical of human primary hyperparathyroidism. We also sought to develop an animal model of hyperparathyroidism and to examine directly cyclin Dl's role in parathyroid tumorigenesis, Parathyroid hormone gene regulatory region-cyclin D1 (PTH-cyclin D1) mice not only developed abnormal parathyroid cell proliferation, but also developed chronic biochemical hyperparathyroidism with characteristic abnormalities in bone and, notably, a shift in the relationship between serum calcium and PTH, Thus, this animal model of human primary hyperparathyroidism provides direct experimental evidence that overexpression of the cyclin D1 oncogene can drive excessive parathyroid cell proliferation and that this proliferative defect need not occur solely as a downstream consequence of a defect in parathyroid hormone secretory control by serum calcium, as had been hypothesized. Instead, primary deregulation of cell-growth pathways carl cause both the hypercellularity and abnormal control of hormonal secretion that are almost inevitably linked together in this common disorder. C1 Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Univ Connecticut, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. EM aarnold@nso2.uchc.edu OI Gronowicz, Gloria/0000-0001-7158-3598 FU NIAMS NIH HHS [P01 AR038933, AR-38933]; NIDDK NIH HHS [DK-11794, DK-48330, DK-52005, P01 DK011794, R01 DK048330, R01 DK052005] NR 40 TC 124 Z9 126 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2001 VL 107 IS 9 BP 1093 EP 1102 DI 10.1172/JCI10523 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 430FT UT WOS:000168564400009 PM 11342573 ER PT J AU Veves, A King, GL AF Veves, A King, GL TI Can VEGF reverse diabetic neuropathy in human subjects? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; NERVE BLOOD-FLOW; PROTEIN-KINASE-C; RATS; ISCHEMIA; STREPTOZOTOCIN; ANGIOGENESIS; TRIAL C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [R01 EY 05110, EY 09178]; NIDDK NIH HHS [DK 59725, DK 36836] NR 21 TC 34 Z9 35 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2001 VL 107 IS 10 BP 1215 EP 1218 DI 10.1172/JCI13038 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 435FU UT WOS:000168867400003 PM 11375408 ER PT J AU Kirkwood, JM Ibrahim, JG Sosman, JA Sondak, VK Agarwala, SS Ernstoff, MS Rao, U AF Kirkwood, JM Ibrahim, JG Sosman, JA Sondak, VK Agarwala, SS Ernstoff, MS Rao, U TI High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with the GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: Results of Intergroup trial E1694/S9512/C509801 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTATIC MALIGNANT-MELANOMA; AMERICAN JOINT COMMITTEE; CD8(+) T-CELLS; CUTANEOUS MELANOMA; ADJUVANT THERAPY; GM2 GANGLIOSIDE; CLINICAL-TRIAL; IN-VITRO; LYMPHOCYTES; IMMUNOTHERAPY AB Purpose: Vaccine alternatives to high-dose interferon alfa-2b therapy (HDI), the current standard adjuvant therapy for high-risk melanoma, are of interest because of toxicity associated with HDI. The GM2 ganglioside is a well-defined melanoma antigen, and anti-GM2 antibodies have been associated with improved prognosis. We conducted a prospective, randomized, intergroup trial to evaluate the efficacy of HDI for 1 year versus vaccination with GM2 conjugated to keyhole limpet hemocyanin and administered with Q5-21 (GMK) for 96 weeks (weekly x 4 then every 12 weeks x 8). Patients and Methods: Eligible patients had resected stage IIB/III melanoma. patients were stratified by sex and number of positive nodes. Primary end points were relapse-free survival (RFS) and overall survival (OS). Results: Eight hundred eighty patients were randomized (440 per treatment group); 774 patients were eligible for efficacy analysis. The trial was closed after interim analysis indicated inferiority of GMK compared with HDI. For eligible patients, HDI provided a statistically significant RFS benefit (hazard ratio [HR] = 1.47, P = .0015) and OS benefit (HR = 1.52, P = .009) for GMK versus HDI. Similar benefit was observed in the intent-to-treat analysis [RFS HR = 1.49; OS HR = 1.38). HDI was associated with a treatment benefit in all subsets of patients with zero to greater than or equal to four positive nodes, but the greatest benefit was observed in the node-negative subset (RFS HR = 2.07; OS HR = 2.71 [eligible population)). Antibody responses to GM2 (ie, titers greater than or equal to 1:80) at days 29, 85, 365, and 720 were associated with a trend toward improved RFS and OS (P-2 = .068 at day 29). Conclusion: This trial demonstrated a significant treatment benefit of HDI versus GMK in terms of RFS and OS in melanoma patients at high risk of recurrence. J Clin Oncol 19:2370-2380. (C) 2001 by American Society of Clinical Oncology. C1 Univ Pittsburgh, Inst Canc, Sch Med, Melanoma Ctr,Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Div Hematol Oncol, Melanoma Ctr, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Inst Canc, Dept Pathol, Melanoma Ctr, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Illinois, Coll Med, Chicago, IL USA. Univ Michigan, Dept Surg, Div Surg Oncol, Ann Arbor, MI 48109 USA. Dartmouth Hitchcock Med Ctr, Div Hematol Oncol, Lebanon, NH 03766 USA. Eastern Cooperat Oncol Grp, Boston, MA USA. SW Oncol Grp, San Antonio, TX USA. RP Kirkwood, JM (reprint author), Univ Pittsburgh, Inst Canc, Sch Med, Melanoma Ctr,Dept Med, 200 Lothrop St, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [CA 39229-16, R03 CA75950-02] NR 42 TC 529 Z9 548 U1 0 U2 4 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 MAY 1 PY 2001 VL 19 IS 9 BP 2370 EP 2380 PG 11 WC Oncology SC Oncology GA 428WE UT WOS:000168484000002 PM 11331315 ER PT J AU Demark-Wahnefried, W Peterson, BL Winer, EP Marks, L Aziz, N Marcom, PK Blackwell, K Rimer, BK AF Demark-Wahnefried, W Peterson, BL Winer, EP Marks, L Aziz, N Marcom, PK Blackwell, K Rimer, BK TI Changes in weight, body composition, and factors influencing energy balance among premenopausal breast cancer patients receiving adjuvant chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEALTH TRIAL FEASIBILITY; QUALITY-OF-LIFE; MINORITY POPULATIONS; MEGESTROL-ACETATE; GAIN; WOMEN; DIAGNOSIS; EXERCISE; THERAPY; REHABILITATION AB Purpose: Weight gain is a common problem among breast cancer patients who receive adjuvant chemotherapy (CT). We undertook a study to determine the causes of this energy imbalance. Patients and Methods: Factors related to energy balance were assessed at baseline (within 3 weeks of diagnosis) and throughout 1 year postdiagnosis among 53 premenopausal women with operable breast carcinoma, Thirty-six patients received CT and 17 received only localized treatment (LT). Measures included body composition (dual energy x-ray absorptiometry), resting energy expenditure (REE; indirect calorimetry), dietary intake (2-day dietary recalls and food frequency questionnaires) and physical activity (physical activity records). Results: Mean weight gain in the LT patients was 1.0 kg versus 2.1 kg in the CT group (P = .02), No significant differences between groups in trend over time were observed for REE and energy intake; however, a significant difference was noted for physical activity (P = .01). Several differences between groups in 1-year change scores were detected. The mean change (+/- SE) in LT versus CT groups and P values for uncontrolled/ controlled (age, race, radiation therapy, baseline body mass index, and end point under consideration) analysis are as follows: percentage of body fat (-0.1 +/- 0.4 v +2.2 +/- 0.6%; P = .001/0.04); fat mass (+0.1 +/- 9.3 v +2.3 +/- 0.7 kg; P = .002/0.04); lean body mass (+0.8 +/- 0.2 v +/- 0.4 +/- 0.3 kg; P = .02/0.30); and leg lean mass (+/- 0.5 +/- 0.1 v -0.2 +/- 0. 1 kg; P = .01/0.11). Conclusion: These data do not support overeating as a cause of weight gain among breast cancer patients who receive CT. The data suggest, however, that CT-induced weigh, gain is distinctive and indicative of sarcopenic obesity (weight gain in the presence of lean tissue loss or absence of lean tissue gain). The development of sarcopenic obesity with evidence of reduced physical activity supports the need for interventions focused on exercise, especially resistance training in the lower body, to prevent weight gain. J Clin Oncol 19:2381-2389. (C) 2001 by American Society of Clinical Oncology. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Demark-Wahnefried, W (reprint author), Duke Univ, Med Ctr, Box 2619, Durham, NC 27710 USA. FU NCI NIH HHS [1K07-CA62215] NR 50 TC 225 Z9 227 U1 2 U2 14 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 MAY 1 PY 2001 VL 19 IS 9 BP 2381 EP 2389 PG 9 WC Oncology SC Oncology GA 428WE UT WOS:000168484000003 PM 11331316 ER PT J AU O'Dwyer, PJ Manola, J Valone, FH Ryan, LM Hines, JD Wadler, S Haller, DG Arbuck, SG Weiner, LM Mayer, RJ Benson, AB AF O'Dwyer, PJ Manola, J Valone, FH Ryan, LM Hines, JD Wadler, S Haller, DG Arbuck, SG Weiner, LM Mayer, RJ Benson, AB TI Fluorouracil modulation in colorectal cancer: Lack of improvement with N-phosphonoacetyl-l-aspartic acid or oral leucovorin or interferon, but enhanced therapeutic index with weekly 24-hour infusion schedule - An Eastern Cooperative Oncology Group/Cancer and Leukemia Group B study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE LEUCOVORIN; MULTICENTER RANDOMIZED TRIAL; FIRST-LINE TREATMENT; PHASE-II TRIAL; BIOCHEMICAL MODULATION; CLINICAL-TRIALS; FOLINIC ACID; N-(PHOSPHONACETYL)-L-ASPARTIC ACID; 5-FLUOROURACIL; CARCINOMA AB Purpose: To investigate mechanism-directed regimens in maximizing the efficacy of fluorouracil (5-FU) in advanced colorected cancer. Patients and Methods: Based on promising phase II data, a randomized comparison of various methods for the biochemical modulation of 5-FU was undertaken in patients with advanced colorectal cancer. The control group received single-agent 5-FU as a 24-hour infusion weekly. Patients (N = 1,120)with no prior chemotherapy for metastatic disease were randomized to one of the following arms: arm A, 5-FU 2,600 mg/m(2) by 24-hour infusion, weekly arm B, N-phosphonoacetyl-l-aspartic acid 250 mg/m(2) day 1, 5-FU 2,500 mg/m(2) by 24-hour infusion day 2, weekly; arm C, 5-FU 600 mg/m2 with oral leucovorin (LV) 125 mg/m(2) hourly for the preceding 4 hours, weekly; arm D, 5-FU 600 mg/m(2) with intravenous (IV) LV 609 mg/m(2), weekly; arm E, 5-fU 750 mg/m(2)/d IV by continuous infusion for 5 days, then 750 mg/m2 weekly, and recombinant interferon alfa-2a 9 million units subcutaneously three times weekly. Median follow-up was 4.8 years. Results: Of the 1,098 assessable patients, 57% had measurable disease. The toxicity of all the regimens was tolerable. Grade 4 or worse toxicity occurred in 11%, 11%, 30%, 24%, and 22% on each arm, respectively; diarrhea was the most common adverse effect. These toxicity patterns favored significantly (P < .001) the 24-hour infusion arms. Median survival (months) by arm was A, 14.8; B, 11.9; C, 13.5; D, 13.6; and E, 15.2. These survival durations did not differ significantly. Conclusion: We conclude that a weekly infusion regimen of 5-FU is significantly less toxic than and as effective as 5-FU bolus regimens modulated by either LV or interferon in patients with metastatic colorectal cancer, J Clin Oncol 19:2413-2421. (C) 2001 by American Society of Clinical Oncology. C1 Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Eastern Cooperat Oncol Grp, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Dartmouth Hitchcock Med Ctr, Hanover, NH USA. Cleveland Metropolitan Gen Hosp, Cleveland, OH 44109 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. New York State Dept Hlth, Roswell Pk Mem Inst, Buffalo, NY 14263 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Chicago, IL 60611 USA. RP O'Dwyer, PJ (reprint author), Univ Penn, Ctr Canc, 51 N 39th St,MAB 103, Philadelphia, PA 19104 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NCI NIH HHS [CA31946, CA14548, CA15488, CA17145, CA21115, CA23318, CA27525, CA37027, CA66636, CACA14958] NR 49 TC 47 Z9 48 U1 0 U2 1 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 MAY 1 PY 2001 VL 19 IS 9 BP 2413 EP 2421 PG 9 WC Oncology SC Oncology GA 428WE UT WOS:000168484000007 PM 11331320 ER PT J AU Burstein, HJ Swanson, SJ Christian, RL McMenamin, ME AF Burstein, HJ Swanson, SJ Christian, RL McMenamin, ME TI Unusual aspects of breast cancer - Case 2. Synchronous bilateral lung and breast cancers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Burstein, HJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 2 Z9 2 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 MAY 1 PY 2001 VL 19 IS 9 BP 2571 EP 2573 PG 3 WC Oncology SC Oncology GA 428WE UT WOS:000168484000025 PM 11331338 ER PT J AU Haffajee, AD Socransky, SS AF Haffajee, AD Socransky, SS TI Relationship of cigarette smoking to the subgingival microbiota SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE smoking; periodontal diseases; periodontitis; pocket depth; attachment level; dental plaque; biofilms; microbial ecology ID EARLY-ONSET PERIODONTITIS; DWELLING OLDER ADULTS; RISK INDICATORS; ATTACHMENT LOSS; DISEASE; PATHOGENS; SMOKERS; INDIVIDUALS; NONSMOKERS; THERAPY AB Background: The relationship of cigarette smoking to the composition of the subgingival microbiota is not clear. Some studies indicated higher levels of certain species in smokers, while other studies failed to detect differences in the microbiota between subjects with different smoking histories. Thus, the purpose of the present investigation was to examine the prevalence, proportions and levels of the subgingival species in adult subjects who were current, past or never smokers. Method: 272 adult subjects ranging in age from 20-86 years with at least 20 teeth were recruited for study. Smoking history was obtained using a questionnaire. Clinical measures were taken at 6 sites per tooth at all teeth excluding third molars at a baseline visit. Subgingival plaque samples tr;ere taken from the mesial surface of all teeth excluding third molars in each subject at baseline and assayed individually for counts of 29 subgingival species using checkerboard DNA-DNA hybridization. Subjects were subset according to smoking history into never (n = 124), past (n = 98) and current smokers (n = 50). Uni-variate and multi-variate analyses were used to seek associations between smoking category and the counts, proportions and prevalence of subgingival species. Results: Greater differences were observed for the prevalence (% of sites colonized) of the test species in the 3 smoking groups than were observed for counts or proportions of total counts. Members of the orange and red complexes including E. nodatum, F. nucleatum ss vincentii, P. intermedia, P. micros, P. nigrescens, B. forsythus, P. gingivalis and T. denticola were significantly more prevalent in current smokers than in the other 2 groups. The difference in prevalence between smokers and non-smokers was due to greater colonization at sites with pocket depth <4 mm. Stepwise multiple linear regression analysis indicated that combinations of the prevalence of 5 microbial species and pack years accounted for 44% of the variance for mean packet depth (p < 0.000001), while the prevalence of 3 microbial taxa along with age, pack years, current smoking and gender accounted for 31% of the variance in mean attachment level (p < 0.000001). The difference in prevalence between current and never smokers of all members of the red complex and 8 of 12 members of the orange complex was significantly greater in the maxilla than in the mandible. Conclusions: The major difference between the subgingival microbiota in subjects with different smoking history nas in the prevalence of species rather than counts or proportions. The greater extent of colonization in smokers appeared to be due to greater colonization at pocket depths <4 mm. Differences in colonization patterns between current and never smokers were greater in the maxilla than in the mandible. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-12108, DE-10977, DE-12861] NR 34 TC 139 Z9 152 U1 1 U2 14 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 MAY PY 2001 VL 28 IS 5 BP 377 EP 388 DI 10.1034/j.1600-051x.2001.028005377.x PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 429QY UT WOS:000168529500001 PM 11350499 ER PT J AU Serino, G Rosling, B Ramberg, P Hellstrom, MK Socransky, SS Lindhe, J AF Serino, G Rosling, B Ramberg, P Hellstrom, MK Socransky, SS Lindhe, J TI The effect of systemic antibiotics in the treatment of patients with recurrent periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE antibiotics; recurrent periodontitis; clinical trial ID ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; SUBGINGIVAL MICROBIOTA; METRONIDAZOLE THERAPY; TETRACYCLINE THERAPY; PLAQUE CONTROL; DISEASE; AMOXICILLIN; GINGIVALIS; SITES AB Background: Subjects with periodontal disease exist who either (i) respond poorly to initial mechanical therapy ("refractory" periodontitis) or (ii) fail to adopt adequate self-performed plaque control techniques and hence develop recurrent disease ("recurrent" periodontitis) at multiple sites during the supportive treatment phase (SPT). Various systemic antibiotic regimens have been tried as adjuncts to the mechanical (re-) treatment of such "difficult to treat"-patients. While most studies indicated a positive outcome of the adjunctive therapy, some clinical investigators reported that this additional measure provided little or no benefit. Aim: The aim of the present investigation was to study the more long term effect of adjunctive antibiotic therapy in the re-treatment of patients with a well defined history of recurrent periodontitis. Material and Methods: 17 subjects with recurrent advanced periodontal disease were, following a baseline examination, subjected to non-surgical therapy including the use of systemic antibiotics (amoxicillin and metronidazole). They were placed in a careful SPT program and re-examined after 1, 3 and 5 years. The examinations included both clinical and microbiological assessments. Results: it was demonstrated that in subjects with advanced and recurrent periodontitis, re-treatment including (i) comprehensive scaling and root planing (SRP), (ii) systemic administration of antibiotics and (iii) meticulous supragingival plaque control by both mechanical and chemical means established periodontal conditions that in the short term (3 years) and in the majority of subjects could be properly maintained by traditional SPT measures. Between 3 and 5 years, however, only 5 of the 17 subjects exhibited stable periodontal attachment levels. Conclusions: Some deep pockets and furcations were most likely inadequately instrumented during the active treatment phase. Microorganisms residing in biofilms left in such locations were probably not sufficiently affected by the 2 weeks of adjunctive antibiotic therapy. It is suggested that removal of certain subgingival deposits, therefore, may require surgical intervention. C1 Univ Gothenburg, Inst Odontol, Dept Periodontol, Gothenburg, Sweden. Forsyth Inst, Boston, MA USA. RP Serino, G (reprint author), Univ Gothenburg, Inst Odontol, Dept Periodontol, Gothenburg, Sweden. FU NIDCR NIH HHS [DE-12861] NR 32 TC 20 Z9 21 U1 0 U2 2 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 MAY PY 2001 VL 28 IS 5 BP 411 EP 418 DI 10.1034/j.1600-051x.2001.028005411.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 429QY UT WOS:000168529500005 PM 11350503 ER PT J AU Ramberg, P Rosling, B Serino, G Hellstrom, MK Socransky, SS Lindhe, J AF Ramberg, P Rosling, B Serino, G Hellstrom, MK Socransky, SS Lindhe, J TI The long-term effect of systemic tetracycline used as an adjunct to non-surgical treatment of advanced periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE adult periodontitis; antibiotics; basic therapy; clinical trial; scaling - root planing; supportive therapy ID PLAQUE CONTROL; 3 MODALITIES; POCKET DEPTH; TOOTH TYPE; THERAPY; DISEASE; ATTACHMENT AB Aim: In the present study both the short- and the long-term effects were evaluated of a treatment that, during the phase of basic therapy, included administration of systemic tetracycline and non-surgical intervention. Material and Methods: 35 adult human subjects with advanced periodontitis, 19 females and 16 males, aged between 24 and 60 years, were included in a test group. 80 age- and sex-matched adult periodontitis subjects were recruited for a control group (42 females and 38 males). A baseline examination included assessment of the following parameters: number of teeth, plaque, bleeding on probing, probing attachment level, probing pocket depth. In radiographs, the distance between the cemento-enamel junction and the alveolar bone crest was determined at all interproximal sites. The subjects were given oral hygiene instruction. The members of the test group were provided with tablets with 250 mg of tetracycline hydrochloride and were instructed to take 1 tablet 4x per day for a period of 3 weeks. No antibiotic was given to the subjects in the control group. During the 3-week interval. all participants received 4-6 sessions of non-surgical periodontal therapy. All subjects were subsequently enrolled in a maintenance care program and were provided with supportive periodontal therapy (SPT) 3-4X per year. Clinical re-examinations were performed after 1, 3, 5 and 13 years. Results: The present investigation demonstrated that tetracycline administered during a 3-week period concomitant with non-surgical treatment enhanced the outcome of mechanical therapy. At the re-examination 1 year after active therapy, there was in the test group an average gain in probing attachment that was almost 3x higher than the gain that occurred in an age and sex matched Control group. Re-examinations after 3. 5. and 13 years of SPT disclosed that this short-term benefit was not maintained in the longer perspective. Conclusion: The beneficial effect of systemically administered tetracycline on probing attachment level occurred in the first year post-therapy. Annual rates. of probing attachment level change from 1 to 13 years did not differ between groups. C1 Univ Gothenburg, Fac Odontol, Dept Periodontol, Gothenburg, Sweden. Forsyth Inst, Boston, MA USA. RP Ramberg, P (reprint author), Univ Gothenburg, Fac Odontol, Dept Periodontol, Gothenburg, Sweden. FU NIDCR NIH HHS [DE-12861] NR 28 TC 27 Z9 27 U1 0 U2 1 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 MAY PY 2001 VL 28 IS 5 BP 446 EP 452 DI 10.1034/j.1600-051x.2001.028005446.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 429QY UT WOS:000168529500010 PM 11350508 ER PT J AU Pollack, MH Zaninelli, R Goddard, A McCafferty, JP Bellew, KM Burnham, DB Iyengar, MK AF Pollack, MH Zaninelli, R Goddard, A McCafferty, JP Bellew, KM Burnham, DB Iyengar, MK TI Paroxetine in the treatment of generalized anxiety disorder: Results of a placebo-controlled, flexible-dosage trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID PANIC DISORDER; PRIMARY-CARE; EXTENDED-RELEASE; DEPRESSION SCALE; DOUBLE-BLIND; OUTPATIENTS; IMIPRAMINE; DISABILITY; BUSPIRONE; EFFICACY AB Background: The objective of this randomized, double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with generalized anxiety disorder (GAD). Method: Male and female outpatients 18 years and older who met DSM-IV criteria for GAD and had baseline scores of at least 20 on the Hamilton Rating Scale for Anxiety (HAM-A) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 8 weeks. The primary efficacy variable was the mean change from baseline in the total score of the HAM-A. Additional key efficacy variables were the change from baseline in the scores of the HAM-A items anxious mood and tension, the anxiety subscale of the Hospital Anxiety and Depression Scale, and the Sheehan Disability Scale (SDS). The proportions of patients fulfilling response and remission criteria at week 8 were also determined. Results: The intent-to-treat population included 324 patients. At week 8, compared with the placebo group (N = 163), the paroxetine group (N = 161) had a significantly greater reduction of GAD symptoms on all of the above-mentioned efficacy variables. On the HAM-A anxious mood item, which encompasses the cardinal symptoms of GAD, significantly greater efficacy was observed from week 1 and on the SDS significantly greater improvement was documented in the domain "social life" as early as week 4 for paroxetine compared with placebo. In both the last-observation-carried-forward and completer data sets, significantly greater proportions of paroxetine-treated patients achieved response or remission by week 8. Treatment with paroxetine was well tolerated, and the number and type of adverse events recorded in the paroxetine group correspond to the known safety profile of this medication. Conclusion: Paroxetine in doses of 20 to 50 mg once daily is effective in the treatment of patients with GAD. Improvement of core symptoms of GAD occurs early and is associated with significant reduction in disability after only 8 weeks of treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Anxiety Disorders Program, Boston, MA 02114 USA. GlaxoSmithKline, Res & Dev, Collegeville, PA USA. Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, New Haven, CT 06508 USA. RP Pollack, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Anxiety Disorders Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. NR 44 TC 165 Z9 168 U1 2 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2001 VL 62 IS 5 BP 350 EP 357 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 440YD UT WOS:000169203500008 PM 11411817 ER PT J AU Safren, SA Rogers, T AF Safren, SA Rogers, T TI Cognitive-behavioral therapy with gay, lesbian, and bisexual clients SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE cognitive-behavioral therapy; lesbian, gay, bisexual clients; coming-out; social phobia ID SOCIAL PHOBIA; PSYCHOTHERAPY AB Cognitive-behavioral therapy (CBT) can be adapted to a wide range of clinical difficulties and presenting problems that face lesbians. gay men, and bisexual persons. The following article presents general guidelines for and two case examples of the use of CBT. The first case is a gay male struggling with social phobia. This case is an example of how to adapt a structured, empirically supported cognitive-behavioral treatment focusing on social phobia to situations that are associated with his sexual orientation. The second is a woman struggling with multiple issues including coming out. This case provides an example of how to add specific cognitive-behavioral techniques to coming-out issues within the context of a more eclectic. longer-term therapy. (C) 2001 John Wiley & Sons, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Fenway Community Hlth, Boston, MA USA. RP Safren, SA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, WACC-815,15 Parkman St, Boston, MA 02114 USA. NR 23 TC 24 Z9 25 U1 0 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD MAY PY 2001 VL 57 IS 5 BP 629 EP 643 DI 10.1002/jclp.1033 PG 15 WC Psychology, Clinical SC Psychology GA 435FG UT WOS:000168866300003 PM 11304703 ER PT J AU Vogels, R Biederman, I Bar, M Lorincz, A AF Vogels, R Biederman, I Bar, M Lorincz, A TI Inferior temporal neurons show greater sensitivity to nonaccidental than to metric shape differences SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID INFEROTEMPORAL CORTEX; VIEWPOINT INVARIANCE; OBJECT RECOGNITION; SPATIAL DISCRIMINATIONS; FEATURES; VISION; IMAGES; MONKEY AB It has long been known that macaque inferior temporal (IT) neurons tend to fire more strongly to some shapes than to others, and that different IT neurons can show markedly different shape preferences. Beyond the discovery that these preferences can be elicited by features of moderate complexity, no general principle of (nonface) object recognition had emerged by which this enormous variation in selectivity could be understood. Psychophysical, as well as computational work, suggests that one such principle is the difference between viewpoint-invariant, nonaccidental (NAP) and view-dependent, metric shape properties (MPs). We measured the responses of single IT neurons to objects differing in either a NAP (namely, a change in a geon) or an MP of a single part, shown at two orientations in depth. The cells were more sensitive to changes in NAPs than in MPs, even though the image variation (as assessed by wavelet-like measures) produced by the former were smaller than the latter. The magnitude of the response modulation from the rotation itself was, on average, similar to that produced by the NAP differences, although the image changes from the rotation were much greater than that produced by NAP differences. Multidimensional scaling of the neural responses indicated a NAP/MP dimension, independent of an orientation dimension. The present results thus demonstrate that a significant portion of the neural code of IT cells represents differences in NAPs rather than MPs. This code may enable immediate recognition of novel objects at new views. C1 Katholieke Univ Leuven, Fac Geneeskunde, Neuro & Psychofysiol Lab, B-3000 Louvain, Belgium. Univ So Calif, Los Angeles, CA 90089 USA. Eotvos Lorand Univ, Budapest, Hungary. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vogels, R (reprint author), Katholieke Univ Leuven, Fac Geneeskunde, Neuro & Psychofysiol Lab, Campus Gasthuisberg,Herestr, B-3000 Louvain, Belgium. EM rufin.vogels@med.kuleuven.ac.be RI Lorincz, Andras/H-4125-2012 OI Lorincz, Andras/0000-0002-1280-3447 NR 32 TC 67 Z9 67 U1 0 U2 4 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAY PY 2001 VL 13 IS 4 BP 444 EP 453 DI 10.1162/08989290152001871 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 438TV UT WOS:000169071100003 PM 11388918 ER PT J AU Aquino, SL Shepard, JAO Ginns, LC Moore, RH Halpern, E Grillo, HC McLoud, TC AF Aquino, SL Shepard, JAO Ginns, LC Moore, RH Halpern, E Grillo, HC McLoud, TC TI Acquired tracheomalacia: Detection by expiratory CT scan SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE trachea; computed tomography; tracheomalacia; trachial stenosis; airway obstruction; diagnosis, computer-assisted ID TRACHEA; DIMENSIONS; CHILDREN AB Purpose: The put-pose of this work was to determine whether cross-sectional area and coronal and sagittal diameter measurements of the trachea between inspiration and end-expiration on CT are significantly different between patients with acquired tracheomalacia and those without this condition. Method: Inspiratory and end-expiratory CT scans of the trachea of 23 normal patients and 10 patients with acquired tracheomalacia were analyzed. Percent changes in cross-sectional area, coronal, and sagittal diameters were calculated. Results: For patients with tracheomalacia, mean percent changes in the upper and middle trachea between inspiration and expiration were 49 and 44% : mean changes in the coronal and sagittal diameters in the upper and middle tracheal were 4 and 10% and 39 and 54%, respectively. Control group mean percent changes in the upper and middle tracheal area were 12 and 14%, respectively, and mean changes in the coronal and sagittal diameters in the upper and middle trachea were 4 and 4% and 11 and 13%, respectively. Significant differences were calculated for changes in cross-sectional area and sagittal diameter between groups (p < 10(-5)). Based on receiver operator curve analysis, a > 18% change in the upper trachea and 28% change in the midtrachea between inspiration and expiration were observed: the probability of tracheomalacia was 89-100%. The probability of tracheomalacia was > 89%, especially if the change in sagittal diameter was > 28%. Conclusion: By measuring changes in tracheal cross-sectional area and sagittal diameters between inspiratory and end-expiratory CT, a significant difference can be identified between normal patients and those with acquired tracheomalacia. C1 Dept Radiol, Boston, MA USA. Dept Pulm & Crit Care Med, Boston, MA USA. Dept Gen Thorac Surg, Boston, MA USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Tilton 201, Boston, MA 02114 USA. NR 13 TC 48 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2001 VL 25 IS 3 BP 394 EP 399 DI 10.1097/00004728-200105000-00011 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 430KN UT WOS:000168573200011 PM 11351189 ER PT J AU Aquino, SL Duncan, G Taber, KH Sharma, A Hayman, LA AF Aquino, SL Duncan, G Taber, KH Sharma, A Hayman, LA TI Reconciliation of the anatomic, surgical, and radiographic classifications of the mediastinum SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE mediastinum; classifications, anatomic; classifications, surgical; classifications, radiographic AB The mediastinum is a complex region that is variously subdivided by radiologists, surgeons and anatomists. This paper describes the most popular of these classifications and color-codes the radiologic and surgical divisions on 22 labeled axial sections of the chest. This allows the reader to quickly name the appropriate location of a lesion on any section. C1 Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Cellular & Mol Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Frensley Ctr Imaging Res, Houston, TX 77030 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Hayman, LA (reprint author), Baylor Coll Med, Dept Radiol, 1 Baylor Plaza, Houston, TX 77030 USA. NR 15 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2001 VL 25 IS 3 BP 489 EP 492 DI 10.1097/00004728-200105000-00026 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 430KN UT WOS:000168573200026 PM 11351204 ER PT J AU Risken, MJ Nadel, ES Brown, DFM AF Risken, MJ Nadel, ES Brown, DFM TI Back pain in a pregnant patient SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID ABRUPTIO PLACENTAE C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2001 VL 20 IS 4 BP 403 EP 406 DI 10.1016/S0736-4679(01)00293-1 PG 4 WC Emergency Medicine SC Emergency Medicine GA 430BR UT WOS:000168554100011 PM 11348822 ER PT J AU Barret, JE Williams, JW Oxman, TE Frank, E Katon, W Sullivan, M Hegel, MT Cornell, JE Sengupta, AS AF Barret, JE Williams, JW Oxman, TE Frank, E Katon, W Sullivan, M Hegel, MT Cornell, JE Sengupta, AS TI Treatment of dysthymia and minor depression in primary care - A randomized trial in patients aged 18 to 59 years SO JOURNAL OF FAMILY PRACTICE LA English DT Article DE depressive disorder; monor depression [non-MESH]; dysitymia [non-MESH]; paroxetine; behavioral treatment [non-MESH]; depression; behavioral treatment paroxetine ID PROBLEM-SOLVING TREATMENT; MAJOR DEPRESSION; MEDICAL OUTCOMES; DISORDERS; PREVALENCE; COMORBIDITY; DISABILITY; PHYSICIANS; PLACEBO; HEALTH AB OBJECTIVE We evaluated the effectiveness of paroxetine and Problem-Solving Treatment for Primary Care (PST-PC) for patients with minor depression or dysthymia. STUDY DESIGN This was an 11-week randomized placebo-controlled trial conducted in primary care practices in 2 communities (Lebanon, NH, and Seattle, Wash). Paroxetine (n=80) or placebo (n=81) therapy was started at 10 mg per day and increased to a maximum 40 mg per day, or PST-PC was provided (n=80). There were 6 scheduled visits for all treatment conditions. POPULATION We included a total of 241 primary care patients with minor depression (n=114) or dysthymia (n=127). Of these, 191 patients (79.3%) completed all treatment visits. OUTCOMES We measured depressive symptoms using the 20-item Hopkins Depression Scale (HSCL-D-20). Remission was scored on the Hamilton Depression Rating Scale (HDRS) as less than or equal to 6 at 11 weeks. We measured functional status with the physical health component (PHC) and mental health component (MHC) of the 36-item Medical Outcomes Study Short Form. RESULTS All treatment conditions showed a significant decline in depressive symptoms over the Ii-week period. There were no significant differences between the interventions or by diagnosis. For dysthymia the remission rate for paroxetine (80%) and PST-PC (57%) was significantly higher than for placebo (44%, P=.008). The remission rate was high for minor depression (64%) and similar for each treatment group, For the MHC there were significant outcome differences related to baseline level for paroxetine compared with placebo, For the PHC there were no significant differences between the treatment groups. CONCLUSIONS For dysthymia, paroxetine and PST-PC improved remission compared with placebo plus nonspecific clinical management. Results varied for the other outcomes measured. For minor depression, the 3 interventions were equally effective; general clinical management (watchful waiting) is an appropriate treatment option. C1 Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03755 USA. Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03755 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Gen Internal Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Geriatr, San Antonio, TX USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Barret, JE (reprint author), Dartmouth Med Sch, Dept Community & Family Med, 7250 Strasenburgh, Hanover, NH 03755 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 36 TC 123 Z9 124 U1 1 U2 10 PU DOWDEN PUBLISHING CORP PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD MAY PY 2001 VL 50 IS 5 BP 405 EP 412 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 431JL UT WOS:000168628000003 PM 11350703 ER PT J AU Silva, JA Leong, GB Weinstock, R Ruiz-Sweeney, M AF Silva, JA Leong, GB Weinstock, R Ruiz-Sweeney, M TI Delusional misidentification and aggression in Alzheimer's disease SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; Capgras syndrome; syndrome of intermetamorphosis; delusional misidentification; aggression; violence; dementia; Alzheimer's disease; psychosis ID CAPGRAS-SYNDROME; BEHAVIORAL DISTURBANCES; PSYCHOTIC SYMPTOMS; DEMENTIA SUFFERERS; FREGOLI SYNDROME; CLASSIFICATION; PHENOMENOLOGY; RISPERIDONE; PREVALENCE; AGITATION AB Alzheimer's disease has: been associated with serious behavioral disturbances including aggressive behaviors and agitation. Aggression in dementia of the Alzheimer's type may be associated with psychotic symptoms, particularly delusional misidentification phenomena. These phenomena are complex and varied in Alzheimer's disease and so far have been only rudimentarily described. In this paper, we explore the association of delusional misidentification and aggression in an individual suffering from Alzheimer's disease. C1 Palo Alto Vet Hlth Care Syst, Palo Alto, CA USA. Western State Hosp, Ctr Forens Serv, Tacoma, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Los Angles Vet Hlth Care Syst, Los Angeles, CA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. RP Silva, JA (reprint author), Palo Alto Vet Hlth Care Syst, Palo Alto, CA USA. NR 60 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAY PY 2001 VL 46 IS 3 BP 581 EP 585 PG 5 WC Medicine, Legal SC Legal Medicine GA 451JC UT WOS:000169798100015 PM 11372992 ER PT J AU Bulkley, G Carr-Locke, DL DiMagno, EP Fernandez-del Castillo, C Fink, AS Helton, WS Lillemoe, K Lindor, K AF Bulkley, G Carr-Locke, DL DiMagno, EP Fernandez-del Castillo, C Fink, AS Helton, WS Lillemoe, K Lindor, K CA SSAT AGE ASGE Consensus Panel TI Management of the biliary tract in acute necrotizing pancreatitis SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Atlanta Vet Adm Med Ctr, Decatur, GA USA. Univ Illinois, Chicago, IL USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, ACC-336, Boston, MA 02114 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY-JUN PY 2001 VL 5 IS 3 BP 221 EP 222 PG 2 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 438JK UT WOS:000169049700001 ER PT J AU Robbins, CJ Bradley, EH Spicer, M AF Robbins, CJ Bradley, EH Spicer, M TI Developing leadership in healthcare administration: A competency assessment tool SO JOURNAL OF HEALTHCARE MANAGEMENT LA English DT Article ID MANAGEMENT; CARE AB Despite the many graduate programs that specialize in health administration, healthcare leaders and practitioners have expressed concern about the quality of preparation of health administration graduates. The purpose of this study was to facilitate one part of an integrated approach to leadership development that spans academic and practitioner settings. The approach was to design a competency assessment tool for early careerists who have two to five years of postgraduate experience and who aspire to fill senior leadership positions in complex, provider-based healthcare organizations. Open-ended interviews with key informants and a comprehensive review of relevant literature were done to identify and categorize a set of competencies relevant to early careerists. Based on data from key informants, specific work experiences and academic courses were mapped to each competency, indicating where and how such competencies might be developed. A simple rating system was then added to assess each competency, which resulted in the completion of the tool. Finally, the tool was piloted in a practitioner setting at the Massachusetts General Hospital Administrative Fellowship Program and in an academic setting at the Yale University Health Management Program. The resulting tool includes 52 competencies categorized into four domains: (1) technical skills (operations, finance, information resources, human resources, and strategic planning/external affairs); (2) industry knowledge (clinical process and healthcare institutions); (3) analytic and conceptual reasoning; and (4) interpersonal and emotional intelligence. Early experience with the tool suggests that it can facilitate career planning among graduate students, early careerists, and their mentors. Further, the tool can help directors of both academic and practitioner programs identify strengths and gaps in their existing curricula or training programs. By offering specific competencies linked to work experiences and graduate courses, the tool is an initial step toward promoting collaborative efforts between academic and practitioner programs. C1 Brandeis Univ, Waltham, MA 02254 USA. Yale Sch Publ Hlth, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Robbins, CJ (reprint author), Brandeis Univ, Waltham, MA 02254 USA. NR 35 TC 12 Z9 12 U1 1 U2 19 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 USA SN 1096-9012 J9 J HEALTHC MANAG JI J. Healthc. Manag. PD MAY-JUN PY 2001 VL 46 IS 3 BP 188 EP 199 PG 12 WC Health Policy & Services SC Health Care Sciences & Services GA 431BV UT WOS:000168612800010 PM 11372221 ER PT J AU Lu, CF Ferzly, M Takagi, J Springer, TA AF Lu, CF Ferzly, M Takagi, J Springer, TA TI Epitope mapping of antibodies to the C-terminal region of the integrin beta(2) subunit reveals regions that become exposed upon receptor activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; POLYMERASE CHAIN-REACTION; CYSTEINE-RICH REPEATS; LIGAND-BINDING REGION; MONOCLONAL-ANTIBODY; LEUKOCYTE-ADHESION; A-DOMAIN; PROPELLER DOMAIN; I-DOMAIN; CR3-DEPENDENT ADHESION AB The cysteine-rich repeats in the stalk region of integrin beta subunits appear to convey signals impinging on the cytoplasmic domains to the ligand-binding headpiece of integrins. We have examined the functional properties of mAbs to the stalk region and mapped their epitopes, providing a structure-function map. Among a panel of 14 mAbs to the beta (2) subunit, one, KIM127, preferentially bound to alpha (L)beta (2) that was activated by mutations in the cytoplasmic domains, and by Mn2+. KIM127 also bound preferentially to the free beta (2) subunit compared with resting alpha (L)beta (2). Activating beta (2) Mutations also greatly enhanced binding of KIM127 to integrins alpha (M)beta (2) and alpha (x)beta (2). Thus, the KIM127 epitope is shielded by the alpha subunit and becomes reexposed upon receptor activation. Three other mAbs, CBR LFA-1/2, MEM48, and KIM185, activated alpha (L)beta (2) and bound equally well to resting and activated alpha (L)beta (2), differentially recognized resting alpha (M)beta (2) and alpha (x)beta (2), and bound fully to activated alpha (M)beta (2) and alpha (x)beta (2). The KIM127 epitope localizes within cysteine-rich repeat 2, to residues 504, 506, and 508. By contrast, the two activating mAbs CBR LFA-1/2 and MEM48 bind to overlapping epitopes involving residues 534,536,541, 543, and 546 in cysteine-rich repeat 3, and the activating mAb KIM185 maps near the end of cysteine-rich repeat 4. The nonactivating mAbs, 6.7 and CBR LFA-1/7, map more N-terminal, to subregions 344-432 and 432-487, respectively. We thus define five different beta (2) stalk subregions, mAb binding to which correlates with effect on activation, and define regions in an interface that becomes exposed upon integrin activation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, 200 Longwood Ave,Room 251, Boston, MA 02115 USA. FU NCI NIH HHS [CA31798] NR 58 TC 117 Z9 117 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 MAY 1 PY 2001 VL 166 IS 9 BP 5629 EP 5637 PG 9 WC Immunology SC Immunology GA 487YH UT WOS:000171906500037 PM 11313403 ER PT J AU Fedyk, ER Jones, D Critchley, HOD Phipps, RP Blieden, TM Springer, TA AF Fedyk, ER Jones, D Critchley, HOD Phipps, RP Blieden, TM Springer, TA TI Expression of stromal-derived factor-1 is decreased by IL-1 and TNF and in dermal wound healing SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; HEMATOPOIETIC PROGENITOR CELLS; HUMAN ENDOTHELIAL-CELLS; LYMPHOCYTE CHEMOATTRACTANT; SDF-1; ANGIOGENESIS; LYMPHOPOIESIS; LOCALIZATION; MYELOPOIESIS; LESTR/FUSIN AB Stromal-derived factor-1 (SDF-1) is a CXC chemokine that is believed to be constitutively expressed by stromal cells of numerous tissues. In this report, we demonstrate that dermal fibroblasts and vessels of noninflamed tissues express SDF-1. Unexpectedly, we found that expression of SDF-1 is regulated by inflammation. Expression of SDF-1 by primary cultures of human gingival fibroblasts is potently inhibited by activated macrophages via secretion of IL-1 alpha and TNF-alpha. Levels of SDF-1 mRNA also decrease in acutely inflamed mouse dermal wounds. We propose that SDF-1 functions as a homeostatic regulator of tissue remodeling, whose expression stabilizes existing dermal architecture. C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. Univ Edinburgh, Ctr Reprod Biol, Dept Reprod & Dev Sci, Edinburgh EH3 9EW, Midlothian, Scotland. Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Environm Med, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Ctr Canc, Rochester, NY 14642 USA. Univ Rochester, Eastman Dent Ctr, Dept Periodontol, Rochester, NY 14627 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, 200 Longwood Ave,Room 251, Boston, MA 02115 USA. RI Jones, Daniel/I-7399-2015 FU NCI NIH HHS [CA1198, T32CA72320]; NHLBI NIH HHS [HL48675, HL56002]; NIDCR NIH HHS [DE11390, DE11785] NR 23 TC 106 Z9 119 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2001 VL 166 IS 9 BP 5749 EP 5754 PG 6 WC Immunology SC Immunology GA 487YH UT WOS:000171906500052 PM 11313418 ER PT J AU Treon, SP Mitsiades, C Mitsiades, N Young, G Doss, D Schlossman, R Anderson, KC AF Treon, SP Mitsiades, C Mitsiades, N Young, G Doss, D Schlossman, R Anderson, KC TI Tumor cell expression of CD59 is associated with resistance to CD20 serotherapy in patients with B-cell malignancies SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE rituximab; drug resistance; complement; CD59; CD55; CD46; multiple myeloma; Fas ligand; MUC1; TRAIL; Waldenstrom macroglobulinemia ID ANTI-CD20 MONOCLONAL-ANTIBODY; NON-HODGKINS-LYMPHOMA; MULTIPLE-MYELOMA CELLS; COMPLEMENT-REGULATORY PROTEINS; FAS APO-1/CD95 LIGAND; LOW-GRADE; WALDENSTROMS MACROGLOBULINEMIA; PROTECTIN CD59; HUMAN-MELANOMA; IN-VIVO AB The anti-CD20 chimeric monoclonal antibody rituximab (Rituxan) is used to treat patients with various B-cell tumors, including patients with plasma cell dyscrasias who have CD20(+) disease. Many patients with CD20(+) disease have either primary unresponsive disease or progress after initially responding to rituximab; therefore, understanding how tumor cells are, or become, resistant to rituximab is of clinical relevance. In this report, we determined whether tumor cells express antigens that block complement-mediated lysis or antibody-dependent cell-mediated cytotoxicity (ADCC) and thereby contribute to rituximab resistance. We demonstrate that expression of the complement regulator CD59 is associated with resistance to rituximab-mediated complement lysis of multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) cell lines. Moreover, neutralization of CD59 using a blocking monoclonal antibody reversed resistance to rituximab-mediated complement lysis of CD20(++) CD59(++) ARH-77 MM cells. In addition, we demonstrate the presence of CD59 and rituximab binding on viable tumor cells from patients with MM and Waldenstrom's macroglobulinemia with progressive disease despite rituximab therapy. Last, we also examined MM and NHL B-cell lines, as well as patient tumor cells, for the expression of other antigens that may have a role in blocking ADCC activity, such as Fas ligand (FasL), MUC1, or TRAIL. FasL, MUC1, and/or TRAIL were coexpressed with complement regulators on many of these cells. These studies therefore show that complement regulators, particularly CD59 and antigens that may block ADCC, are present on various B-cell tumors and associated with rituximab resistance in patients. A prospective, clinical study is assessing the role of these antigens in mediating rituximab resistance. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, M555,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P0-1 CA 78378] NR 43 TC 149 Z9 154 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2001 VL 24 IS 3 BP 263 EP 271 DI 10.1097/00002371-200105000-00011 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 436ZY UT WOS:000168966800011 PM 11394505 ER PT J AU Treon, SP Agus, TB Link, B Rodrigues, G Molina, A Lacy, MQ Fisher, DC Emmanouilides, M Richards, AI Clark, B Lucas, MS Schlossman, R Schenkein, D Lin, B Kimby, E Anderson, KC Byrd, JC AF Treon, SP Agus, TB Link, B Rodrigues, G Molina, A Lacy, MQ Fisher, DC Emmanouilides, M Richards, AI Clark, B Lucas, MS Schlossman, R Schenkein, D Lin, B Kimby, E Anderson, KC Byrd, JC TI CD20-directed antibody-mediated immunotherapy induces responses and facilitates hematologic recovery in patients with Waldenstrom's macroglobulinemia SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE serotherapy; antibody-mediated immunotherapy Waldenstrom's macroglobulinemia lymphoplasmacytic lymphoma; rituximab ID ANTI-CD20 MONOCLONAL-ANTIBODY; B-CELLS; MULTIPLE-MYELOMA; LOW-GRADE; PHASE-II; LYMPHOMA; THERAPY; ORIGIN; CD20 AB Waldenstrom's macroglobulinemia (WM, lymphoplasmacytic lymphoma) is a B-cell lymphoproliferative disorder in which CD20 is expressed on tumor cells from most patients. Several small studies have suggested a benefit from the anti-CD20 monoclonal antibody rituximab (Rituxan, MabThera) in patients with WM. In this retrospective study, we examined the outcome of 30 previously unreported patients with WM who received treatment with single-agent rituximab (median age 60; range 32-83 years old). The median number of prior treatments for these patients was 1 (range 0-6), and 14 patients (47%) received a nucleoside analogue before rituximab therapy. Patients received a median of 4.0 (1-11.3) infusions of rituximab (375 mg/m(2)). Three patients received steroids with their infusions for prophylaxis of rituximab-related infusion syndrome. Overall, treatment was well tolerated. Median immunoglobulin M (IgM) levels for all patients declined from 2,403 mg/dL (range 720-7639 mg/dL) to 1,525 mg/dL (range 177-5,063 mg/dL) after rituximab therapy (p = 0.001), with 8 of 30 (27%) and 18 of 30 (60%) patients demonstrating >50% and >25% decline in IgM, respectively. Median bone marrow lymphoplasmacytic (BM LPC) cell involvement declined from 60% (range 5-90%) to 15% (range 0-80%) for 17 patients for whom pre- and post-BM biopsies were performed (p < 0.001). Moreover, 19 of 30 (63%) and 15 of 30 (50%) patients had an increase in their hematocrit (HCT) and platelet (PLT) counts, respectively. Before rituximab therapy, 7 of 30 (23.3%) patients were either transfusion or erythropoietin dependent, whereas only 1/30 (3.3%) patients required transfusions (no erythropoietin) after rituximab. Overall responses after treatment with rituximab were as follows: 8 (27%) and 10 (33%) of the patients achieved a partial (PR) and a minor (MR) response, respectively, and an additional 9 (30%) of patients demonstrated stable disease (SD). No patients attained a complete response. The median time to treatment failure for responding (PR and MR) patients was 8.0 months (mean 8.4; range 3-20+ months), and 5.0 months (mean 6.1; range 3-12+ months) for patients with SD, These studies therefore demonstrate that rituximab is an active agent in WM. Marked increases in HCT and PLT counts were noted for most patients, including patients with WM who had MR or SD. A prospective clinical trial to more completely define the benefit of single-agent rituximab in patients with WM has been initiated by many of our centers. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Mayo Clin, Rochester, MN USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Cincinnati, Cincinnati, OH USA. Kaiser Permanente, Vallejo, CA USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. New England Med Ctr, Boston, MA 02111 USA. Huddinge Univ Hosp, S-14186 Huddinge, Sweden. RP Treon, SP (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, M555,44 Binney St, Boston, MA 02115 USA. NR 20 TC 106 Z9 108 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2001 VL 24 IS 3 BP 272 EP 279 DI 10.1097/00002371-200105000-00012 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 436ZY UT WOS:000168966800012 PM 11394506 ER PT J AU Willsky, GR Goldfine, AB Kostyniak, PJ McNeill, JH Yang, LQ Khan, HR Crans, DC AF Willsky, GR Goldfine, AB Kostyniak, PJ McNeill, JH Yang, LQ Khan, HR Crans, DC TI Effect of vanadium(IV) compounds in the treatment of diabetes: in vivo and in vitro studies with vanadyl sulfate and bis(maltolato)oxovandium(IV) SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article; Proceedings Paper CT Annual Meeting of the Canadian-Chemistry-Society CY MAY 28-31, 2000 CL CALGARY, CANADA SP Canadian Chem Soc DE vanadyl sulfate; bis(maltolato)oxovandium(IV); BMOV; diabetes; EPR ID INSULIN MIMETIC AGENT; FREE COPPER; IN-VITRO; COMPLEXES; MELLITUS; SERUM; TRANSFERRIN; METABOLISM; CHEMISTRY; STABILITY AB Vanadyl sulfate (VOSO4) was given orally to 16 subjects with type 2 diabetes mellitus for 6 weeks at a dose of 25, 50, or 100 mg vanadium (V) daily [Goldfine et al., Metabolism 49 (2000) 1-12]. Elemental V was determined by graphite furnace atomic absorption spectrometry (GFAAS). There was no correlation of V in serum with clinical response, determined by reduction of mean fasting blood glucose or increased insulin sensitivity during euglycemic clamp. To investigate the effect of administering a coordinated V, plasma glucose levels were determined in streptozotocin (STZ)-induced diabetic rats treated with the salt (VOSO4) or the coordinated V compound bis(maltolato)oxovandium(IV) (abbreviated as VO(malto)(2)) administered by intraperitoneal (i.p.) injection. There was no relationship of blood V concentration with plasma glucose levels in the animals treated with VOSO4, similar to our human diabetic patients. However, with VO(malto)(2) treatment, animals with low plasma glucose tended to have high blood V. To determine if V binding to serum proteins could diminish biologically active serum V, binding of both VOSO4 and VO(malto)(2) to human serum albumin (HSA), human apoTransferrin (apoHTf) and pig immunoglobulin (IgG) was studied with EPR spectroscopy. Both VOSO4 and VO(malto)(2) bound to HSA and apoHTf forming different V-protein complexes, while neither V compound bound to the IgG. VOSO4 and VO(malto)(2) showed differences when levels of plasma glucose and blood V in diabetic rodents were compared, and in the formation of V-protein complexes with abundant serum proteins. These data suggest that binding of V compounds to ligands in blood, such as proteins, may affect the available pool of V for biological effects. (C) 2001 Elsevier Science B.V. All rights reserved. C1 SUNY Buffalo, Sch Med & Biomed Sci, Toxicol Res Ctr, Buffalo, NY 14214 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada. Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA. RP Willsky, GR (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Toxicol Res Ctr, Buffalo, NY 14214 USA. FU NCRR NIH HHS [M01 RR-02635-15]; NIDDK NIH HHS [R01 DK47462-05]; NIGMS NIH HHS [R01 GM40525] NR 32 TC 136 Z9 140 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD MAY PY 2001 VL 85 IS 1 BP 33 EP 42 DI 10.1016/S0162-0134(00)00226-9 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 440YY UT WOS:000169205300005 PM 11377693 ER PT J AU Rosand, J Schwamm, LH AF Rosand, J Schwamm, LH TI Management of brain edema complicating stroke SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Review ID CEREBRAL BLOOD-FLOW; CONVERTING ENZYME-INHIBITION; INTRA-CRANICAL PRESSURE; ACUTE ISCHEMIC STROKE; INTRACRANIAL-PRESSURE; HEMISPHERIC INFARCTION; AUTO-REGULATION; DECOMPRESSIVE CRANIECTOMY; BARRIER PERMEABILITY; PERFUSION-PRESSURE AB Ischemic brain edema, the accumulation of fluid within the brain parenchyma following stroke, is a predictable consequence of both ischemic and hemorrhagic strokes. Its development is the result of injury to both brain parenchyma and the blood vessels supplying the parenchyma Ischemic stroke produces both cytotoxic (intracellular) edema, which develops when cells are damaged, and vasogenic (extracellular) edema, which arises from injury to structures essential to blood-brain barrier integrity. An understanding of the distinction between cytotoxic and vasogenic edema is essential in preventing secondary brain injury, since the treatments for the two entities differ. The development of new brain imaging technologies has advanced our understanding of brain edema. Both computed tomograph! (CT) and magnetic resonance imaging (MRI) can detect edema. Specific MRI sequences such as diffusion-weighted imaging can distinguish cytotoxic and vasogenic subtypes, and thereby detect ischemic cell injury within minutes of the onset of symptoms. Brain edema causes neurologic deterioration predominantly through its mass effect, which leads to distortion of the intracranial contents and impairment of both regional and global cerebral blood flow (CBF). Edema may also cause local tissue dysfunction. Management of the intracranial hypertension and tissue shifts caused by ischemic brain swelling is based on the fundamental relationship between pressure, now, and resistance. Interventions are directed at preserving CBF and preventing secondary brain injury. Strategies include reducing intracranial blood volume with hypocapnia, reducing brain volume with osmotic agents, reducing cerebral metabolism with hypothermia and barbiturates, reducing resistance with rheologic agents, increasing blood pressure with vasoconstrictors, and expanding the cranial vault with decompressive surgery. All individual therapies must be used as part of a structured approach that involves frequent serial neurologic assessments, quantitative measures of pressure, non; and resistance, and prespecified protocols for intervention. C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK-915, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 104 TC 5 Z9 5 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0885-0666 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD MAY-JUN PY 2001 VL 16 IS 3 BP 128 EP 141 DI 10.1046/j.1525-1489.2001.00128.x PG 14 WC Critical Care Medicine SC General & Internal Medicine GA 437EZ UT WOS:000168979200003 ER PT J AU Webster, C Tiribelli, C Ostrow, JD AF Webster, C Tiribelli, C Ostrow, JD TI An improved method for isolation of unconjugated bilirubin from rat and dog bile SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID BINDING AB Radiolabeled unconjugated bilirubin (UCB) is currently prepared by biosynthetic labeling of bilirubin in fistula bile from precursor-labeled delta -aminolevulinic acid (ALA) in rats or dogs. With existing methods, yields of labeled UCB from the bile are generally less than 50%. We here report modifications of the original method of Ostrow et al (Ostrow JD: Hammaker L, Schmid R. The preparation of crystalline bilirubin-C-14. J Clin invest 1961;40: 1442-52) that result in improvement of yields to 72% from both dog and rat bile. The modifications include the initial deproteination of bile with a reverse-phase C18 cartridge, removal of ethanol before alkaline hydrolysis to avoid esterification of UCB, and adjustments for the high proportion of non-glucuronide UCB conjugates in dog bile not precipitated as lead salts. These improvements should save significantly on both costs and animal usage. C1 Northwestern Univ, Div Gastroenterol Hepatol, Chicago, IL 60611 USA. Vet Affairs Lakeside Med Ctr, Res Serv, Chicago, IL USA. Univ Trieste, Dept Biochem Biophys & Chem Macromol, Trieste, Italy. Univ Amsterdam, Acad Med Ctr, Dept Gastroenterol Hepatol, NL-1105 AZ Amsterdam, Netherlands. RP Ostrow, JD (reprint author), VA Puget Sound Hlth Care Syst, Res Serv, GI Hepatol Lab, Seattle Div, 151L,1660 S Columbian Way, Seattle, WA 98108 USA. NR 17 TC 7 Z9 8 U1 0 U2 4 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 MAY PY 2001 VL 137 IS 5 BP 370 EP 373 DI 10.1067/mlc.2001.114544 PG 4 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 432JT UT WOS:000168689000009 PM 11329535 ER PT J AU Fox, JG Handt, L Xu, SL Shen, ZL Dewhirst, FE Paster, BJ Dangler, C Lodge, K Motzel, S Klein, H AF Fox, JG Handt, L Xu, SL Shen, ZL Dewhirst, FE Paster, BJ Dangler, C Lodge, K Motzel, S Klein, H TI Novel Helicobacter species isolated from rhesus monkeys with chronic idiopathic colitis SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; TAMARINS SAGUINUS-OEDIPUS; SP-NOV; CAMPYLOBACTER-FENNELLIAE; COLON-CANCER; INBRED MICE; HEPATICUS; INFECTION; DIARRHEA; BILIS AB Chronic, idiopathic diffuse colitis is a well recognised clinical and pathological entity in captive rhesus monkeys, Six rhesus monkeys were diagnosed with clinically debilitating, chronic diarrhoea, Histologically; colonic tissues were characterised as chronic, moderate to severe colitis and typhlitis, with diffuse mononuclear inflammation of lamina propria, reactive lymphoid hyperplasia and multifocal micro-abscesses. Colonic tissues were cultured for Salmonella spp, and Shigella spp,; all results were negative. Samples were negative for Clostridium difficile A and B toxins, and special stains of colonic tissue for acid-fast bacteria were also negative. The sis diarrhoeic monkeys tested gave negative results for serum IgG antibodies to herpes B virus, STLV SRV and SIV. Colonic tissue from the six diarrhoeic and two clinically normal monkeys with histologically confirmed colitis from the same colony were also subjected to micro-aerobic culture. Micro-aerobic cultures from all eight monkeys incubated at 37 degreesC and 42 degreesC revealed pinpoint or spreading colonies on antibiotic-containing media. Bacteria were identified as gramnegative, oxidase positive and urease negative. Of the nine strains characterised biochemically; two separate biotypes (corresponding to different species by 16S rRNA analysis) mere identified. One biotype (type 1), from non-diarrhoeic monkeys and the second biotype (type 2) from diarrhoeic animals with subclinical chronic colonic inflammation, differed by catalase activity, ability to reduce nitrate to nitrite and sensitivity to cephalothin, Complete 16S rRNA analysis of five of the nine strains characterised biochemically indicated that the organisms isolated were two novel Helicobacter spp, By electron microscopy, these novel helicobacters had spiral morphology with bipolar sheathed flagella, This is the first report describing the isolation of novel Helicobacter spp, from inflamed colons of rhesus monkeys. Studies are needed to determine whether these novel Helicobacter spp, play a causal role in the initiation and progression of chronic colitis in macaques, Further microbiological and histological analysis of this chronic idiopathic colitis syndrome in macaques may prove useful in understanding the aetiology and pathogenesis of inflammatory bowel disease in man. C1 MIT, Cambridge, MA 02139 USA. Merck Res Labs, W Point, PA USA. Forsyth Inst, Boston, MA USA. RP Fox, JG (reprint author), MIT, Cambridge, MA 02139 USA. FU NCI NIH HHS [CA67529]; NIDCR NIH HHS [DE10374]; NIDDK NIH HHS [R01 DK 52413] NR 35 TC 38 Z9 38 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-2615 J9 J MED MICROBIOL JI J. Med. Microbiol. PD MAY PY 2001 VL 50 IS 5 BP 421 EP 429 PG 9 WC Microbiology SC Microbiology GA 426FQ UT WOS:000168339500005 PM 11339249 ER PT J AU Davia, K Bernobich, E Ranu, HK del Monte, F Terracciano, CMN MacLeod, KT Adamson, DL Chaudhri, B Hajjar, RJ Harding, SE AF Davia, K Bernobich, E Ranu, HK del Monte, F Terracciano, CMN MacLeod, KT Adamson, DL Chaudhri, B Hajjar, RJ Harding, SE TI SERCA2a overexpression decreases the incidence of aftercontractions in adult rabbit ventricular myocytes SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE sarcoplasmic reticulum; SERCA2a; adenovirus; myocyte; gene therapy; beta-adrenoceptor; aftercontractions ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; ADENOVIRAL GENE-TRANSFER; STAGE HEART-FAILURE; GUINEA-PIG; CARDIAC MYOCYTES; RAT; EXPRESSION; CALCIUM; CARDIOMYOCYTES; MYOCARDIUM AB Slow relaxation and poor contractile response to increasing stimulation frequency in failing human heart have been strongly linked to a decrease in the activity of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a). Restoration of SERCA2a levels using gene transfer has beneficial effects on contractile function but, like beta -adrenoceptor stimulation. could potentially produce excess SR Ca2-. arrhythmias and cell death, We have examined the effects of SERCA2a overexpression in adult rabbit cardiac myocytes. and compared changes in relaxation with those following beta -adrenoceptor stimulation. Myocytes were infected with an adenovirus carrying both SERCA2a and green fluorescent protein (GFP) for positive identification of infected cells. Myocyte survival was significantly enhanced in the infected cultures, There was a reduction in both time-to-peak contraction and time-to-50%, relaxation (R50) 48 h after infection. Time-to-90%, relaxation (R90) was particularly improved (noninfected 516 +/- 41 ms. AD.SERCA2a-GFP 230 +/- 23 ms, n = 7 preparations P < 0.001). There was also a decreased incidence of aftercontractions in Ad.SERCA2a-GFP infected myocytes (21 +/- 5% v 41 +/- 4% in controls. P < 0.01). This contrasts with beta -adrenoceptor stimulation, which reduced R50 but prolonged R90 by 158 +/- 76 ms (P < 0.02. n = 16). At higher stimulation frequencies (2-3 Hz) contraction amplitude and SR calcium content were increased and diastolic contracture was reduced following SERCA2a overexpression. Overall, increasing levels of SERCA2a resulted in an improvement in systolic and diastolic function and a reduction in cell death and arrhythmic aftercontractions. SERCA2a overexpression therefore lacks the detrimental effects associated with some other inotropic interventions. (C) 2001 Academic Press. C1 Imperial Coll, Natl Heart & Lung Inst, Sch Med, London SW3 6LY, England. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harding, SE (reprint author), Imperial Coll, Natl Heart & Lung Inst, Sch Med, Dovehouse St, London SW3 6LY, England. EM sian.harding@ic.ac.uk FU NHLBI NIH HHS [HL 50361, HL 57623] NR 39 TC 54 Z9 59 U1 1 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2001 VL 33 IS 5 BP 1005 EP 1015 DI 10.1006/jmcc.2001.1368 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 433PP UT WOS:000168769200014 PM 11343422 ER PT J AU Kawamata, H McLean, PJ Sharma, N Hyman, BT AF Kawamata, H McLean, PJ Sharma, N Hyman, BT TI Interaction of alpha-synuclein and synphilin-1: effect of Parkinson's disease-associated mutations SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE FRET; human neuroglioma cells; Parkinson's disease; synphilin-1; alpha-synuclein ID RESONANCE ENERGY-TRANSFER; LEWY BODIES; AGGREGATION; INCLUSIONS; DEMENTIA AB alpha -Synuclein is a major component of Lewy bodies, a neuropathological feature of Parkinson's disease. Two alpha -synuclein mutations, Ala53Thr and Ala30Pro, are associated with early onset, familial forms of the disease. Recently, synphilin-1, a protein found to interact with alpha -synuclein by yeast two hybrid techniques, was detected in Lewy bodies. In this study we report the interaction of alpha -synuclein and synphilin-1 in human neuroglioma cells using a sensitive fluorescence resonance energy transfer technique. We demonstrate that the C-terminus of alpha -synuclein is closely associated with the C-terminus of synphilin-1. A weak interaction occurs between the N-terminus of alpha -synuclein and synphilin-1. The familial Parkinson's disease associated mutations of alpha -synuclein (Ala53Thr and Ala30Pro) also demonstrate a strong interaction between their C-terminal regions and synphilin-1. However, compared with wild-type alpha -synuclein, significantly less energy transfer occurs between the C-terminus of Ala53Thr alpha -synuclein and synphilin-1, suggesting that the Ala53Thr mutation alters the conformation of alpha -synuclein in relation to synphilin-1. C1 Massachusetts Gen Hosp East, Dept Neurol, Alzheimers Dis Res Unit, Boston, MA 02129 USA. RP Hyman, BT (reprint author), 149 13th St,Room 6405, Charlestown, MA 02129 USA. NR 14 TC 48 Z9 52 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2001 VL 77 IS 3 BP 929 EP 934 DI 10.1046/j.1471-4159.2001.00301.x PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 429WX UT WOS:000168541900022 PM 11331421 ER PT J AU Lenz, G Goncalves, D Luo, ZJ Avruch, J Rodnight, R Neary, JT AF Lenz, G Goncalves, D Luo, ZJ Avruch, J Rodnight, R Neary, JT TI Extracellular ATP stimulates an inhibitory pathway towards growth factor-induced cRaf-1 and MEKK activation in astrocyte cultures SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ATP; cross-talk; ERK; FGF; MAP kinase; Raf ID PROTEIN-KINASE-C; RAT CORTICAL ASTROCYTES; CELL-CYCLE ARREST; MAP KINASE; EXCHANGE FACTOR; PURINERGIC RECEPTORS; SIGNALING PATHWAYS; P-2Y PURINOCEPTOR; TROPHIC ACTIONS; JUN KINASE AB ATP, acting via P2Y, G protein-coupled receptors (GPCRs), is a mitogenic signal and also synergistically enhances fibroblast growth factor-2 (FGF-2)-induced proliferation in astrocytes. Here, we have examined the effects of ATP and FGF-2 cotreatment on the main components of the extracellular-signal regulated protein kinase (ERK) cascade, cRaf-1, MAP/ERK kinase (MEK) and ERK, key regulators of cellular proliferation. Surprisingly, ATP inhibited activation of cRaf-1 by FGF-2 in primary cultures of rat cortical astrocytes. The inhibitory effect did not diminish MEK and ERK activation; indeed, cotreatment resulted in a greater initial activation of ERK. ATP inhibition of cRaf-1 activation was not mediated by an increase in cyclic AMP levels or by protein kinase C activation. ATP also inhibited the activation of cRaf-1 by other growth factors, epidermal growth factor and platelet-derived growth factor, as well as other MEK1 activators stimulated by FGF-2, MEK kinase 1 (MEKK1) and MEKK2, Serotonin, an agonist of another GPCR coupled to ERK, did not inhibit FGF-2-induced cRaf-1 activation, thereby indicating specificity in the ATP-induced inhibitory cross-talk. These findings suggest that ATP stimulates an inhibitory activity that lays upstream of MEK activators and inhibits growth factor-induced activation of cRaf-1 and MEKKs. Such a mechanism might serve to integrate the actions of receptor tyrosine kinases and P2Y-GPCRs. C1 Vet Affairs Med Ctr, Res Serv 151, Miami, FL 33125 USA. Univ Fed Rio Grande Sul, Dept Biofis, Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Dept Bioquim, Porto Alegre, RS, Brazil. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL USA. Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL USA. RP Neary, JT (reprint author), Vet Affairs Med Ctr, Res Serv 151, 1201 NW 16th St, Miami, FL 33125 USA. RI Lenz, Guido/A-7618-2008 NR 49 TC 24 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2001 VL 77 IS 4 BP 1001 EP 1009 DI 10.1046/j.1471-4159.2001.00299.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 433QQ UT WOS:000168771600005 PM 11359865 ER PT J AU Qiu, ZH Strickland, DK Hyman, BT Rebeck, GW AF Qiu, ZH Strickland, DK Hyman, BT Rebeck, GW TI Elevation of LDL receptor-related protein levels via ligand interactions in Alzheimer disease and in vitro SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE alpha 2-macroglobulin; amyloid precursor protein; apolipoprotein E; astrocyte; immunoblot; lipoprotein ID AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E RECEPTOR; NEURITE OUTGROWTH; GROWTH-FACTOR; HUMAN BRAIN; ALPHA(2)-MACROGLOBULIN RECEPTOR; CEREBROSPINAL-FLUID; GENETIC ASSOCIATION; CYTOSOLIC ADAPTER; BETA-PROTEIN AB The low-density lipoprotein (LDL) receptor-related protein (LRP) is a multifunctional receptor in the CNS that binds both apolipoprotein E (apoE) and activated alpha2-macroglobulin (alpha 2M*); all 3 proteins are genetically associated with Alzheimer disease (AD). In this study we found an 85% increase in LRP levels in human AD brain frontal cortex, along with an increased level of the LRP ligands, apoE. and (alpha 2M. We speculated that LRP levels might be increased in response to the increased levels of its ligands, apoE, and alpha 2M*. To test this hypothesis we examined the effects of alpha 2M* on LRP in primary cultures. Treatment of neurons with alpha 2M* significantly increased LRP levels (by 92%). This increase was prevented by coculture with receptor-associated protein (RAP), which blocks binding of LRP ligands to LRP. Native alpha 2M or RAP alone did not change LRP levels in vitro. We also found that alpha 2M* stimulated activation of astrocytes in vitro and promoted the levels of LRP by 65%. These data indicate 1) the LRP ligand alpha 2M* increases levels of LRP in primary neuronal and astrocytic cultures, 2) alpha 2M*-induction of LRP levels in vitro depends on binding to LRP, and 3) LRP levels are increased in AD brain, perhaps in response to the increased levels of alpha 2M. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimer Res Unit, Charlestown, MA 02129 USA. Amer Red Cross, Holland Lab, Rockville, MD USA. RP Rebeck, GW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimer Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG12406, AG14473] NR 61 TC 31 Z9 32 U1 0 U2 0 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 MAY PY 2001 VL 60 IS 5 BP 430 EP 440 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 433XW UT WOS:000168786800004 PM 11379818 ER PT J AU Louis, DN Sasaki, H Zlatescu, MC Cairncross, JG AF Louis, DN Sasaki, H Zlatescu, MC Cairncross, JG TI Histopathological-molecular genetic correlations in referral pathologist-diagnosed "low-grade oligodendroglioma". SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. London Reg Canc Ctr, London, ON N6A 4L6, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2001 VL 60 IS 5 MA 123 BP 534 EP 534 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 433XW UT WOS:000168786800134 ER PT J AU Cortez, S Vonsattel, JP Stopa, EG Chang, HT AF Cortez, S Vonsattel, JP Stopa, EG Chang, HT TI Familial Pick's disease without pick bodies: A report of 2 cases with severe cerebral atrophy. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Brown Univ, Sch Med, Providence, RI 02912 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2001 VL 60 IS 5 MA 177 BP 547 EP 547 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 433XW UT WOS:000168786800187 ER PT J AU McGibbon, CA Krebs, DE AF McGibbon, CA Krebs, DE TI Age-related changes in lower trunk coordination and energy transfer during gait SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MECHANICAL ENERGY; EXPENDITURE PROBLEM; FRACTIONS APPROACH; HUMAN LOCOMOTION; MOTOR PATTERNS; HUMAN WALKING; LINK SYSTEM; MUSCLE; BALANCE; MOVEMENTS AB The effects of aging on lower trunk (trunk-low-back joint-pelvis) coordination and energy transfer during locomotion has received little attention; consequently, there are scant biomechanical data available for comparison with patient populations whose upper body movements may be impaired by orthopaedic or neurologic disorders. To address this problem, we analyzed gait data from a cross-sectional sample of healthy adults (n = 93) between 20 and 90 yr old (n = 44 elderly, >50 yr old; n = 49 young, <50 yr old). Gait characteristics of elders were mostly typical: gait speed of elders (1.13 +/- 0.20 m/s) was significantly (P = 0.007) lower than gait speed of young subjects (1.20 +/- 0.18 m/s). Although elders had less low-back (trunk relative to pelvis) range of motion (ROM; P = 0.013) during gait than young subjects, no age-related differences were detected in absolute trunk and pelvis ROM or peak pitch angles during gait. Despite similar upper body postures, there was a strong association between age and pelvis-trunk angular velocity phase angle (r = 0.48, P < 0.001) with zero phase occurring at approximately 55 yr of age; young subjects lead with the pelvis while elderly subjects lead with the trunk. Age related changes in gait speed and low-back ROM were unable to explain the above findings. The trunk-leading strategy used by elders resulted in a sense reversal of the low-back joint power curve and increased (P = 0.013) the mechanical energy expenditure required for eccentric control of the lower trunk musculature during stance phase of gait. These data suggest an age-related change in the control of lower trunk movements during gait that preserves upper body posture and walking speed but requires a leading trunk and higher mechanical energy demands of lower trunk musculature-two factors that may reduce the ability to recover from dynamic instabilities. The behavioral and motor control aspects of these findings may be important for understanding locomotor impairment compensations in aging humans and in quantifying falls risk. C1 Massachusetts Gen Hosp, Biomot Lab, Dept Orthopaed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Biomot Lab, Dept Orthopaed, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG-11255] NR 53 TC 47 Z9 49 U1 2 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2001 VL 85 IS 5 BP 1923 EP 1931 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 432DC UT WOS:000168675100013 PM 11353009 ER PT J AU Brownell, AL Chen, YI Canales, K Owen, C Livni, E Cicchetti, F Sanchec-Pernaute, R Isacson, O AF Brownell, AL Chen, YI Canales, K Owen, C Livni, E Cicchetti, F Sanchec-Pernaute, R Isacson, O TI Is there a coupling between dopaminergic function and oxidative metabolism in Parkinson's disease? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. McLean Hosp, Neurogenerat Lab, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 50 BP 14P EP 14P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900051 ER PT J AU Babich, JW Smith, MP Kozikowski, AP Bonab, AA Livni, E Fischman, AJ AF Babich, JW Smith, MP Kozikowski, AP Bonab, AA Livni, E Fischman, AJ TI CNS pharmacodynamics of a novel cocaine medication: Pet studies with C-11 cocaine. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Biostream Inc, Cambridge, MA USA. Georgetown Univ, Washington, DC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 55 BP 15P EP 16P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900056 ER PT J AU Dragotakes, SC Callahan, RJ AF Dragotakes, SC Callahan, RJ TI A rapid gas chromatographic method for the detection of tetrabutylammonium bicarbonate in preparations of FDG. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 66 BP 19P EP 19P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900067 ER PT J AU Aquino, SL Asmuth, J Weise, S Fischman, AJ AF Aquino, SL Asmuth, J Weise, S Fischman, AJ TI Evaluation of mediastinal disease in post therapy cancer patients by non linear automatic registration of thoracic CT and PET datasets. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Sarnoff Corp, Princeton, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 128 BP 35P EP 35P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900129 ER PT J AU Carter, EA Burker, M Tompkins, RG Fischman, AJ AF Carter, EA Burker, M Tompkins, RG Fischman, AJ TI Effect of burn injury to rats on bone uptake of Tc-99m MDP, F-18, I-125 tetracycline and (18)FDG. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Shriners Hosp Children, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 147 BP 39P EP 40P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900148 ER PT J AU Correia, JA Burnham, CA Kaufman, DE Fischman, AJ AF Correia, JA Burnham, CA Kaufman, DE Fischman, AJ TI An LSO-based detector element for a multiplanar small-animal PET instrument. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 208 BP 56P EP 56P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900209 ER PT J AU Bogdanov, AA Simonova, ML Sergeyev, NS Weissleder, R AF Bogdanov, AA Simonova, ML Sergeyev, NS Weissleder, R TI Cell-surface targeted metallothionein mutants in nuclear imaging of marker protein expression. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 286 BP 77P EP 77P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900287 ER PT J AU Bonab, AA Alpert, NM Livni, E Meltzer, PC Madras, BK Fischman, AJ AF Bonab, AA Alpert, NM Livni, E Meltzer, PC Madras, BK Fischman, AJ TI Human DAT binding measurement with C-11-Altropane. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 794 BP 184P EP 184P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900695 ER PT J AU Bonab, AA Meltzer, PC Alpert, NM Burker, M Dragotakes, SD Barrow, SB Madras, BK Fischman, AJ AF Bonab, AA Meltzer, PC Alpert, NM Burker, M Dragotakes, SD Barrow, SB Madras, BK Fischman, AJ TI Human brain spect imaging with a highly selective DAT ligand Tc-99m-(15)O05t. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Organix Inc, Woburn, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 896 BP 210P EP 210P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900795 ER PT J AU Madras, BK Meltzer, PC Babich, JW Bonab, AA Fischman, AJ AF Madras, BK Meltzer, PC Babich, JW Bonab, AA Fischman, AJ TI Occupancy of the dopamine transporter by a transport inhibitor, as measured by PET imaging, is predictive of therapeutic efficacy for Parkinsonism. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 898 BP 210P EP 210P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900797 ER PT J AU Brownell, AL Chen, YI Canales, KE Powers, RT Dedeoglu, A Jenkins, BG AF Brownell, AL Chen, YI Canales, KE Powers, RT Dedeoglu, A Jenkins, BG TI Coupling of glucose utilization to neuronal toxicity - An ultra high resolution PET study. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 919 BP 215P EP 216P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900818 ER PT J AU Tokareva, E Alpert, NM Weise, S Barrow, SA Fischman, AJ AF Tokareva, E Alpert, NM Weise, S Barrow, SA Fischman, AJ TI Chronic statin treatment enhances endothelial nitric oxide synthase-dependent cerebral blood flow augmentation by L-arginine. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 918 BP 215P EP 215P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900817 ER PT J AU Fakhri, GE Kijewski, MF Moore, SC Hilson, JB Becker, JA Killiany, R Albert, MS Johnson, KA AF Fakhri, GE Kijewski, MF Moore, SC Hilson, JB Becker, JA Killiany, R Albert, MS Johnson, KA TI Discrimination between normal controls and precilincal Alzheimer's disease using quantitative brain SPECT with OSEM reconstruction. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 945 BP 222P EP 222P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900844 ER PT J AU Ranch, SL Shin, LM Dougherty, DD Alpert, NM Baer, L Jenike, MA Fischman, AJ AF Ranch, SL Shin, LM Dougherty, DD Alpert, NM Baer, L Jenike, MA Fischman, AJ TI Regional cerebral blood flow during symptom provocation in obsessive-compulsive disorder: Predictors of response to pharmacotherapy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 1007 BP 238P EP 238P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900906 ER PT J AU Ranch, SL Dougherty, DD Cosgrove, GR Cassem, EH Alpert, NM Price, BH Nierenberg, AA Mayberg, HS Baer, L Jenike, MA Fischman, AJ AF Ranch, SL Dougherty, DD Cosgrove, GR Cassem, EH Alpert, NM Price, BH Nierenberg, AA Mayberg, HS Baer, L Jenike, MA Fischman, AJ TI Cerebral metabolic predictors of response to anterior cingulotomy for obsessive-compulsive disorder. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 1006 BP 238P EP 238P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900905 ER PT J AU Maresca, KP Kronauge, JF Babich, JW Burker, MA McCusker, CD Fischman, AJ AF Maresca, KP Kronauge, JF Babich, JW Burker, MA McCusker, CD Fischman, AJ TI Infection imaging with novel chemotactic peptide antagonists. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Biostream Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI McCusker, Catherine/G-2795-2010 OI McCusker, Catherine/0000-0001-9580-3612 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 1107 BP 263P EP 264P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821901004 ER PT J AU Callahan, RJ Dragotakes, SC Barrow, SA Burker, MA Tokareva, EA Fischman, AJ AF Callahan, RJ Dragotakes, SC Barrow, SA Burker, MA Tokareva, EA Fischman, AJ TI A phase I clinical trial of the DAT ligand Tc-99m-O(15)O5T. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 1125 BP 268P EP 268P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821901022 ER PT J AU Livni, E Burker, M Hillier, S Rubin, RH Fischman, AJ AF Livni, E Burker, M Hillier, S Rubin, RH Fischman, AJ TI Tissue pharmacokinetics of C-11 labeled stavudine. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 1386 BP 334P EP 334P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821901282 ER PT J AU Fischman, AJ Hsu, H Carter, EA Yu, YM Guerrero, JL Young, VR Alpert, NM Tompkins, RG AF Fischman, AJ Hsu, H Carter, EA Yu, YM Guerrero, JL Young, VR Alpert, NM Tompkins, RG TI Measurement of canine skeletal muscle blood flow by positron emission tomography with (H2O)-O-15. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 1404 BP 339P EP 339P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821901300 ER PT J AU Alpert, NM Yu, YM Young, VR Tompkins, RG Fischman, AJ AF Alpert, NM Yu, YM Young, VR Tompkins, RG Fischman, AJ TI Local protein synthesis rate in skeletal muscle: Measurements in normal subjects and burn patients. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 2001 VL 42 IS 5 SU S MA 1420 BP 342P EP 343P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821901316 ER PT J AU Schecter, A Dai, LC Papke, O Prange, J Constable, JD Matsuda, M Thao, VD Piskac, AL AF Schecter, A Dai, LC Papke, O Prange, J Constable, JD Matsuda, M Thao, VD Piskac, AL TI Recent dioxin contamination from Agent Orange in residents of a southern Vietnam city SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID DIABETES-MELLITUS; DIBENZOFURAN LEVELS; CHLORINATED DIOXIN; SERUM DIOXIN; EXPOSURE; VETERANS; WORKERS; MORTALITY; SAMPLES; COHORT AB Marked elevation of dioxin associated with the herbicide Agent Orange was recently found in 19 of 20 blood samples from persons living in Bien Hoa, a large city in southern Vietnam. This city is located near an air base that was used for Agent Orange spray missions between 1962 and 1970. A spill of Agent Orange occurred at this air base more than 30 years before blood samples were collected in 1999. Samples were collected, frozen, and sent to a World Health Organization-certified dioxin laboratory fm congener-specific analysis as part of a Vietnam Red Cross project. Previous analyses of more than 2200 pooled blood samples collected in the 1990s identified Bien Hoa as one of several southern Vietnam areas with persons having elevated blood dioxin levels from exposure to Agent Orange. In sharp contrast to this study, our previous research showed decreasing tissue dioxin levels over time since 1970. Only the dioxin that contaminated Agent Orange, 2,3, 7, 8-tetrachlmodibenzo-p-dioxin (TCDD), was elevated in the blood of 19 of 20 persons sampled from Bien Hoa. A comparison pooled sample from 100 residents of Hanoi, where Agent Orange was not used, measured blood TCDD levels of 2 parts per trillion (ppt). TCDD levels of up to 271 ppt, a 135-fold increase, were found in Bien Hoa residents. TCDD contamination was also found in some nearby soil and sediment samples. Persons new to this region and children born after Agent Orange spraying ended also had elevated TCDD levels. This TCDD uptake was recent and occurred decades after spraying ended. We hypothesize that a major route of current and past exposures is from the movement of dioxin from soil into river sediment, then into fish, and from fish consumption into people. C1 Univ Texas, Houston Sch Publ Hlth, Dallas Satellite,Environm Sci Discipline, SW Med Ctr, Dallas, TX 75390 USA. Viet Nam Red Cross, Hanoi, Vietnam. ERGO Lab, Hamburg, Germany. Griffith Univ, Natl Res Ctr Environm Toxicol, Brisbane, Qld 4111, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Ehime Univ, Matsuyama, Ehime, Japan. Hanoi Univ Technol, Inst Environm Sci & Technol, Hanoi, Vietnam. RP Schecter, A (reprint author), Univ Texas, Houston Sch Publ Hlth, Dallas Satellite,Environm Sci Discipline, SW Med Ctr, 6011 Harry Hines Blvd, Dallas, TX 75390 USA. NR 35 TC 54 Z9 61 U1 6 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAY PY 2001 VL 43 IS 5 BP 435 EP 443 DI 10.1097/00043764-200105000-00002 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 432MA UT WOS:000168694600002 PM 11382178 ER PT J AU Troulis, MJ Kaban, LB AF Troulis, MJ Kaban, LB TI Endoscopic approach to the ramus/condyle unit: Clinical applications SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID MANAGEMENT; FRACTURES; OSTEOTOMY; SURGERY AB Purpose: The purpose of this report is to describe use of an endoscopic technique for exposure of the mandibular ramus/condyle unit (RCU) to facilitate reconstructive jan: procedures. Patients and Methods: This is a retrospective evaluation of 10 patients with diagnoses of idiopathic condylar resorption (n = 2), subcondylar fracture (n = 5), mandibular prognathism (n = 1), condylar hyperplasia (n = 1), and mandibular asymmetry (n = 1), who underwent endoscopic exposure of the RCU. Results: All 10 patients had successful reconstruction of the RCU using the endoscopic approach. The procedures performed included the following: condylectomy (n = 5 sides), costochondral graft reconstruction (n = 4 sides), reduction of subcondylar fracture (n = 5 sides), and mandibular ramus osteotomy (n = 4 sides), Mean operating time was 84 minutes. No patients had marginal mandibular nerve weakness or other complications. Conclusion: This case series demonstrates the feasibility of endoscopic access to the RCU. The procedures can be performed with no increase in operative time and with minimal morbidity. (C) 2001 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Sch Dent Med, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Harvard Univ, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, Sch Dent Med, Warren Bldg 1201,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 49 Z9 54 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2001 VL 59 IS 5 BP 503 EP 509 DI 10.1053/joms.2001.22706 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 428AK UT WOS:000168438800008 PM 11326371 ER PT J AU Seldin, EB AF Seldin, EB TI Mandibular distraction force: Laboratory data and clinical correlation SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Seldin, EB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2001 VL 59 IS 5 BP 544 EP 545 DI 10.1053/joms.2001.22873 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 428AK UT WOS:000168438800018 ER PT J AU Dentinger, CM Heinrich, NL Bell, BP Fox, LM Katz, DJ Culver, DH Shapiro, CN AF Dentinger, CM Heinrich, NL Bell, BP Fox, LM Katz, DJ Culver, DH Shapiro, CN TI A prevalence study of hepatitis A virus infection in a migrant community: Is hepatitis A vaccine indicated? SO JOURNAL OF PEDIATRICS LA English DT Article ID OUTBREAK AB Background: The Advisory Committee on Immunization Practices recommends routine hepatitis A vaccination of children living in communities with high rates of hepatitis A. Rates among children living in migrant farm worker families are unknown. Methods: Participants recruited from the 1243 migrant children aged 2 to 18 years in Okeechobee County, Florida, were administered a questionnaire. A blood sample was taken for testing for antibodies to hepatitis A virus (anti-HAV), and hepatitis A vaccine was administered. Results: Of 244 (20%) participating children, 125 (51%) were anti-HAV-positive. Seropositivity increased with age from 34% (2- to 5-year-olds) to 81% (greater than or equal to 14-year-olds) (P < .0001). In multivariate analysis, age (odds ratio [OR] = 1.2/year; 95% CI = 1.1 to 1.3), having a Mexican-born father (OR = 12.2; 95% CI = 2.2 to 227.9), and age on moling to the United States (OR = 1.3/year; 95% CI = 1.0 to 1.6) were independently associated with anti-HAV positivity. Among US-born children aged 2 to 5 years who had never left the United States, 33% were anti-HAV-positive. Conclusions: Anti-HAV prevalence among migrant children in Okeechobee County including the youngest US-born children, is high, indicating ongoing transmission of HAV. Children in this and other US migrant communities may benefit from hepatitis A vaccination. C1 CDCP, Hepatitis Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. CDCP, Epidem Intelligence Serv, Epidemiol Program Off, Atlanta, GA USA. Okeechobee Cty Hlth Dept, Okeechobee, FL USA. Florida Dept Hlth, Miami, FL USA. Massachusetts Gen Hosp, Dept Pediat, HST, Serv Pediat, Boston, MA 02114 USA. RP Bell, BP (reprint author), CDCP, Hepatitis Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Mailstop G-37,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 14 TC 11 Z9 11 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2001 VL 138 IS 5 BP 705 EP 709 DI 10.1067/mpd.2001.112652 PG 5 WC Pediatrics SC Pediatrics GA 431LY UT WOS:000168633800021 PM 11343047 ER PT J AU Dluhy, RG Anderson, B Harlin, B Ingelfinger, J Lifton, R AF Dluhy, RG Anderson, B Harlin, B Ingelfinger, J Lifton, R TI Glucocorticoid-remediable aldosteronism is associated with severe hypertension in early childhood SO JOURNAL OF PEDIATRICS LA English DT Article ID DIAGNOSIS; SYNTHASE AB Objectives: To review the childhood course of glucocorticoid-remediable aldosteronism (GRA) in order to provide management guidelines for hypertension in children. Methods: Records for 20 children with GRA (aged 1 month to 18 years; 16 with hypertension) were retrospectively reviewed. Results: Of the 16 children with GRA who del eloped hypertension, 50% had moderate-severe hypertension (blood pressure [BP] >99th centile for age and sex); 32% had mild hypertension (BP >95th and <99th centile), and 18% had borderline normal BP (BP >90th and <95th centile). Eight of 16 children with hypertension who received directed monotherapy (glucocorticoid suppression or aldosterone receptor/sodium epithelial channel antagonists) maintained BP below the 90th centile. Three additional subjects receiving a combination of directed therapies or a combination of directed therapies and nifedipine were unable to achieve BP control. At GRA diagnosis, 5 of 8 children were normokalemic, and plasma renin activity was suppressed in 5 of 5 subjects. Conclusions: Clinicians should have a high index of suspicion for GRA, especially in children with severe hypertension and a positive family history of early-onset hypertension and/or premature hemorrhagic stroke. Directed monotherapy is often successful in controlling BP in GRA. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol & Hypertens, Boston, MA 02115 USA. MassGen Hosp Children, Div Pediat Nephrol, Boston, MA USA. Yale Univ, Sch Med, Dept Genet Internal Med & Mol Biophys & Biochem, New Haven, CT USA. RP Dluhy, RG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol & Hypertens, 221 Longwood Ave, Boston, MA 02115 USA. NR 11 TC 31 Z9 32 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2001 VL 138 IS 5 BP 715 EP 720 DI 10.1067/mpd.2001.112648 PG 6 WC Pediatrics SC Pediatrics GA 431LY UT WOS:000168633800023 PM 11343049 ER PT J AU Tarazi, FI Zhang, K Baldessarini, RJ AF Tarazi, FI Zhang, K Baldessarini, RJ TI Long-term effects of olanzapine, risperidone, and quetiapine on dopamine receptor types in regions of rat brain: Implications for antipsychotic drug treatment SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MESSENGER-RNA EXPRESSION; DIFFERENTIAL REGULATION; D-4 RECEPTORS; SCHIZOPHRENIA; CLOZAPINE; HALOPERIDOL; CORTEX; NEUROLEPTICS; HIPPOCAMPUS; OCCUPANCY AB Changes in members of the dopamine (DA) D-1-like (D-1, D-5) and D-2-like (D-2, D-3, D-4) receptor families in rat forebrain regions were compared by quantitative in vitro receptor autoradiography after prolonged treatment (28 days) with the atypical antipsychotics olanzapine, risperidone, and quetiapine. Olanzapine and risperidone, but not quetiapine, significantly increased D-2 binding in medial prefrontal cortex (MPC; 67% and 34%), caudate-putamen (CPu; average 42%, 25%), nucleus accumbens (NAc; 37%, 28%), and hippocampus (HIP; 53%, 30%). Olanzapine and risperidone, but not quetiapine, produced even greater up-regulation of D-4 receptors in CPu (61%, 37%), NAc (65%, 32%), and HIP (61%, 37%). D-1-like and D-3 receptors in all regions were unaltered by any treatment, suggesting their minimal role in mediating actions of these antipsychotics. The findings support the hypothesis that antipsychotic effects of olanzapine and risperidone are partly mediated by D-2 receptors in MPC, NAc, or HIP, and perhaps D-4 receptors in CPu, NAc, or HIP, but not in cerebral cortex. Selective up-regulation of D-2 receptors by olanzapine and risperidone in CPu may reflect their ability to induce some extrapyramidal effects. Inability of quetiapine to alter DA receptors suggests that nondopaminergic mechanisms contribute to its antipsychotic effects. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA USA. Harvard Univ, Sch Med, Psychiat & Neurosci Program, Consolidated Dept, Boston, MA USA. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-34006, MH-47370] NR 49 TC 73 Z9 74 U1 1 U2 5 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 MAY PY 2001 VL 297 IS 2 BP 711 EP 717 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 422FM UT WOS:000168107900032 PM 11303062 ER PT J AU Caplan, D AF Caplan, D TI Functional neuroimaging studies of syntactic processing SO JOURNAL OF PSYCHOLINGUISTIC RESEARCH LA English DT Article; Proceedings Paper CT 13th Annual CUNY Conference on Human Sentence Processing CY MAR 30-APR 01, 2000 CL LA JOLLA, CALIFORNIA SP CUNY DE functional neuroanatomy; syntactic processing ID VERBAL WORKING-MEMORY; SENTENCE COMPREHENSION; PET; LOCALIZATION; ACTIVATION; COMPONENTS; LANGUAGE; BRAIN; FMRI; FORM AB This paper reviews studies of the functional neuroanatomy of syntactic processing using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), focusing on interpretability of studies and the model of functional neuroanatomy that emerges from existing work. It is argued that existing studies suggest a specialization for one aspect of syntactic processing in the left inferior frontal cortex in proficient language users, with variability in this localization across the entire population. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. FU NIA NIH HHS [AG09661]; NIDCD NIH HHS [DC02146] NR 29 TC 67 Z9 69 U1 2 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6905 J9 J PSYCHOLINGUIST RES JI J. Psycholinguist. Res. PD MAY PY 2001 VL 30 IS 3 BP 297 EP 320 DI 10.1023/A:1010495018484 PG 24 WC Linguistics; Psychology, Experimental SC Linguistics; Psychology GA 463VB UT WOS:000170497000007 PM 11523276 ER PT J AU Sangeorzan, BJ AF Sangeorzan, BJ TI Guest editorial - Limb loss prevention and prosthetic engineering SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material C1 VA Puget Sound Hlth Care Syst, Limb Loss Ctr Excellence, Seattle, WA 98108 USA. RP Sangeorzan, BJ (reprint author), VA Puget Sound Hlth Care Syst, Limb Loss Ctr Excellence, 1660 S Columbian Way,152, Seattle, WA 98108 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2001 VL 38 IS 3 BP VI EP VII PG 2 WC Rehabilitation SC Rehabilitation GA 445HM UT WOS:000169452100001 PM 11440268 ER PT J AU Choudhury, SR Reiber, GE Pecoraro, JA Czerniecki, JM Smith, DG Sangeorzan, BJ AF Choudhury, SR Reiber, GE Pecoraro, JA Czerniecki, JM Smith, DG Sangeorzan, BJ TI Postoperative management of transtibial amputations in VA hospitals SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE immediate postoperative prostheses; removable rigid dressings; rigid dressings; soft dressings; transtibial amputations AB Rigid plaster dressings and immediate postoperative prostheses (IPOP) in patients undergoing transtibial amputations have been reported to reduce pain and healing time, prevent knee flexion contractures, and expedite early ambulation compared to soft dressings. Yet, despite the reported benefits, surgical adoption of (conventional) rigid dressings a.nd IPOP has been inconsistent. The purpose of this study was to determine the current postoperative transtibial amputation dressing practices in VA hospitals. A six-item questionnaire was sent to 134 surgeons at the 117 VA hospitals where transtibial amputations were performed in fiscal year 1999. Responses were received from 83% of the surgeons. During the 1999 study year, surgeons performing transtibial amputations used soft dressings on 67% of patients, conventional rigid dressings with no intent to apply a foot attachment on 14% of patients, removable rigid dressings on 14% of patients, and IPOP (almost exclusively without a foot) on 5% of patients. The application of a rigid dressing or IPOP did not correlate well with the total number of transtibial amputations performed by the surgeon, hospital bed size, or academic affiliation. C1 VA Puget Sound Health Care Syst, Hlth Serv R&D 152, Seattle, WA 98108 USA. VA Puget Sound Health Care Syst, VA Ctr Excellence Limb Loss Prevent & Prosthet En, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Orthopaed, Seattle, WA 98195 USA. Univ Washington, Dept Sports Med & Rehabil, Seattle, WA 98195 USA. RP Reiber, GE (reprint author), VA Puget Sound Health Care Syst, Hlth Serv R&D 152, Seattle, WA 98108 USA. NR 30 TC 14 Z9 15 U1 4 U2 4 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2001 VL 38 IS 3 BP 293 EP 298 PG 6 WC Rehabilitation SC Rehabilitation GA 445HM UT WOS:000169452100003 PM 11440260 ER PT J AU Reiber, GE Smith, DG Carter, J Fotieo, G Deery, HG Sangeorzan, JA Lavery, L Pugh, J Peter-Riesch, B Assal, JP del Aguila, M Diehr, P Patrick, DL Boyko, EJ AF Reiber, GE Smith, DG Carter, J Fotieo, G Deery, HG Sangeorzan, JA Lavery, L Pugh, J Peter-Riesch, B Assal, JP del Aguila, M Diehr, P Patrick, DL Boyko, EJ TI A comparison of diabetic foot ulcer patients managed in VHA and non-VHA settings SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE amputation; diabetes mellitus; diabetic foot; foot ulcers; treatment; wound healing ID LOWER-EXTREMITY AMPUTATIONS; RISK-FACTORS; LIMB AMPUTATION; MELLITUS AB Objective: To compare patients with diabetes and new onset foot ulcers treated in Veterans Health Administration (VHA) and non-VHA settings. Methods: The treatment of patients with new onset diabetic foot ulcers was prospectively monitored in three VHA and three non-VHA hospitals and outpatient settings until ulcer healing, amputation, or death. Results: Of the 302 individuals enrolled in this study, 47% were veterans receiving VHA care. There: were no significant differences between veterans and nonveterans in baseline wound classification, diabetes severity, or comorbid conditions. Veterans received significantly fewer sharp debridements, total contact casts, and custom inserts than their nonveteran counterparts, and they had significantly more x-rays, local saline irrigations, IV antibiotics, and prescriptions for bed rest. The percentage of amputations was higher in veterans but did not achieve statistical significance. Conclusions: Many commonly held stereotypes of veteran men were not found. Veterans and nonveterans with foot ulcers were similar in terms of health and foot history, diabetes severity, and comorbid conditions. There was considerable variation in treatment of diabetic foot ulcers between VHA and non-VHA care. Yet this variation did not result in statistically significant differences in ulcer outcomes. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Reiber, GE (reprint author), VA Puget Sound Hlth Care Syst, 152,1660 S Columbian Way, Seattle, WA 98108 USA. OI Pugh, Jacqueline/0000-0003-4933-141X NR 21 TC 14 Z9 14 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2001 VL 38 IS 3 BP 309 EP 317 PG 9 WC Rehabilitation SC Rehabilitation GA 445HM UT WOS:000169452100005 PM 11440262 ER PT J AU Legro, MW Reiber, GE Czerniecki, JM Sangeorzan, BJ AF Legro, MW Reiber, GE Czerniecki, JM Sangeorzan, BJ TI Recreational activities of lower-limb amputees with prostheses SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE lower-limb amputee; lower-limb prosthesis; physical function; recreational activities AB Ninety-two (92) persons with lower-limb amputations who regularly used prostheses responded to a survey that included questions about preferred recreational activities. This article describes the variety of activities selected by these men and women aged 20 to 87 years. Of the activities that were of high importance, 74% to 88% could be performed. Those activities assigned moderate to low importance were less often reported as able to be performed. The activities that require high energy level were more problematic for performance. The diversity of identified activities (n = 166) underscores the value of learning about amputees' activity preferences when making prosthetic prescription decisions. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. VA Ctr Excellence Limb Loss Prevent & Prosthet En, RR&D, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. HSR&D, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Phys Med & Rehabil, Seattle, WA USA. Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98195 USA. RP Legro, MW (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,152, Seattle, WA 98108 USA. NR 5 TC 25 Z9 28 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2001 VL 38 IS 3 BP 319 EP 325 PG 7 WC Rehabilitation SC Rehabilitation GA 445HM UT WOS:000169452100006 PM 11440263 ER PT J AU Digiovanni, CW Holt, S Czerniecki, JM Ledoux, WR Sangeorzan, BJ AF Digiovanni, CW Holt, S Czerniecki, JM Ledoux, WR Sangeorzan, BJ TI Can the presence of equinus contracture be established by physical exam alone? SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE contracture; equinus; gastrocnemius ID LIMITED JOINT MOBILITY; DIABETIC FOOT ULCERATION; CEREBRAL-PALSY; ANKLE; NEUROPATHY; PRESSURES; DEFORMITY; CHILDREN; STRENGTH; MUSCLE AB The condition in which ankle dorsiflexion is restricted is known as equinus contracture (EC). Equinus contracture is purported to be associated with a number of clinical conditions. However, there are no data to support or refute a clinician's ability to diagnose EC by clinical exam. We prospectively evaluated the maximum ankle dorsiflexion with the knee fully extended in 68 people (34 patients with isolated fore- or midfoot pain and 34 asymptomatic subjects) both by clinical exam and by a custom-designed ankle goniometer. We compared the likelihood of agreement of the clinical impression (equinus, no equinus) to the maximum ankle dorsiflexion measured with the instrument at two different numerical definitions of EC (less than or equal to5 degrees and less than or equal to 10 degrees of maximum dorsiflexion). When all subjects were included and equinus defined as less than or equal to5 degrees of ankle dorsiflexion, a clinician's ability to detect the equinus when it is truly present is 77.8%. If equinus is defined as less than or equal to 10 degrees, this ability increases to 97.2%. Alternatively, if equinus is not present, as defined by less than or equal to5 degrees, then a clinician's ability to correctly diagnose no equinus is 93.8%. If equinus is defined to less than or equal to 10 degrees, this ability decreases to 68.8%. C1 RR&D Ctr Excellence Limb Loss Prevent & Prosthet, Seattle, WA 98108 USA. Univ Washington, Dept Orthoped & Sports Med, Seattle, WA 98195 USA. RP Sangeorzan, BJ (reprint author), VA Puget Sound Hlth Care Syst, Limb Loss Ctr Excellence, 1660 S Columbian Way,152, Seattle, WA 98108 USA. RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 36 TC 14 Z9 14 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2001 VL 38 IS 3 BP 335 EP 340 PG 6 WC Rehabilitation SC Rehabilitation GA 445HM UT WOS:000169452100008 PM 11440265 ER PT J AU Mayfield, JA Reiber, GE Maynard, C Czerniecki, JM Caps, MT Sangeorzan, BJ AF Mayfield, JA Reiber, GE Maynard, C Czerniecki, JM Caps, MT Sangeorzan, BJ TI Survival following lower-limb amputation in a veteran population SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE amputation; cardiovascular disease; diabetes; epidemiology; race; renal disease; survival; veterans ID LOWER-EXTREMITY; MORTALITY; AMPUTEES; GANGRENE; AFFAIRS AB Goal: We sought to describe the common demographic and comorbid conditions that affect survival following nontraumatic amputation. Methods: Veterans Administration hospital discharge records for 1992 were linked with death records. The most proximal level during the first hospitalization in 1992 was used for analysis. Demographic information (age, race) and comorbid diagnosis (cardiovascular, cerebrovascular, and renal disease) were used for Kaplan-Meier curves to describe survival following amputation. Main Outcome Measure: Death. Results: Mortality risk increased with advanced age, more proximal amputation level, and renal and cardiovascular disease, and decreased for African Americans. No increased risk for persons: with diabetes was noted in the first year following amputation but the risk increased thereafter A higher risk of mortality in the first year was noted for renal disease, cardiovascular disease,;md proximal amputation level. Conclusion: Survival following lower-limb amputation is impaired by advancing age, cardiovascular and renal disease, and proximal amputation level. Also, a small survival advantage is seen for African Americans and those with diabetes. C1 Puget Sound Hlth Care Syst, Ctr Excellence Amputat Prosthet & Limb Loss Preve, Seattle, WA USA. Seattle Epidemiol Res Informat Ctr, Seattle, WA USA. RP Sangeorzan, BJ (reprint author), VA Puget Sound Hlth Care Syst, Limb Loss Ctr Excellence, 1660 S Columbia Way 152, Seattle, WA 98108 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 18 TC 68 Z9 70 U1 1 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2001 VL 38 IS 3 BP 341 EP 345 PG 5 WC Rehabilitation SC Rehabilitation GA 445HM UT WOS:000169452100009 PM 11440266 ER PT J AU Mayfield, JA Caps, MT Reiber, GE Maynard, C Czerniecki, JM Sangeorzan, BJ AF Mayfield, JA Caps, MT Reiber, GE Maynard, C Czerniecki, JM Sangeorzan, BJ TI Trends in peripheral vascular procedures in the Veterans Health Administration, 1989-1998 SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE angioplasty; diabetes; epidemiology; vascular bypass; veterans ID DEPENDENT DIABETES-MELLITUS; LOWER-EXTREMITY AMPUTATION; BYPASS-SURGERY; UNITED-STATES; RISK-FACTORS; DISEASE; AFFAIRS AB Objective: To assess trends in peripheral vascular procedures performed in Veterans Health Administration (VHA) facilities. Methods: All discharges with peripheral vascular procedures recorded for 1989-1998 were analyzed. The VHA user population was used to calculate age-specific rates. Trends were evaluated using frequency tables and Poisson regression. Results: The VHA had 55,916 discharges with peripheral vascular procedures performed almost exclusively in men. Indications included peripheral vascular disease (53.7%), gangrene (19.3%), surgical complications (13.3%), and ulcers and infection (9.6%). The VHA age- specific rates were higher than US population rates for persons 45 to 64 years, similar for those 65 to 74 years, and lower for those 75 years and older. The age-specific rates declined slightly over the 10 years of observation, with the greatest decline noted in men age 45 to 65. Conclusion: The VHA provides almost 8% of all US peripheral vascular procedures in males. The WA age-specific rates differ from the US rates with a shift to younger patients. The rates decreased for all age groups between 1989-1998. C1 Puget Sound Hlth Care Syst, Ctr Excellence Prosthet Engn & Limb Loss Prevent,, Seattle, WA USA. VA Epidemiol Res & Informat Ctr, ERIC, Seattle, WA USA. RP Sangeorzan, BJ (reprint author), VA Puget Sound Hlth Care Syst, Limb Loss Ctr Excellence, 1660 S Columbian Way,152, Seattle, WA 98108 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 19 TC 1 Z9 1 U1 1 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2001 VL 38 IS 3 BP 347 EP 356 PG 10 WC Rehabilitation SC Rehabilitation GA 445HM UT WOS:000169452100010 PM 11440267 ER PT J AU Harper, SL Letko, E Samson, CM Zafirakis, P Sangwan, V Nguyen, Q Yu, H Baltatzis, S Foster, CS AF Harper, SL Letko, E Samson, CM Zafirakis, P Sangwan, V Nguyen, Q Yu, H Baltatzis, S Foster, CS TI Wegener's granulomatosis: The relationship between ocular and systemic disease SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE Wegener's granulomatosis; eye; vasculitis ID PULMONARY ANGIITIS; DIAGNOSTIC-VALUE; LIMITED FORMS; CYCLOPHOSPHAMIDE; MANIFESTATIONS; CLASSIFICATION; EXPERIENCE; SCLERITIS; THERAPY; ANCA AB Objective, Wegener's granulomatosis (WG) is an etiologically obscure entity with multiple systemic manifestations;. Ocular involvement is present in up to 58% of patients with WG. We describe a series of patients with ocular manifestations of WG to evaluate the presence of ocular lesions in the setting of systemic WG and to determine the value of ocular inflammation in the diagnosis of WG. Methods. A computerized database was used to generate a list of patients cared for in the Ocular Immunology Service of the Massachusetts Eye and Ear Infirmary during the 10 year period 1988-98 with a diagnosis of Wegener's granulomatosis. A detailed chart review was undertaken to determine demographic characteristics, history, initial manifestation of WG, initial ocular presentation, biopsy results, laboratory testing results, treatment, total followup period, and final outcome. Results, Forty-seven patients diagnosed with WG were identified. Twenty-eight were women (59.6%) 19 were men (40.4%). The average age was 53 years (range 18-90). Patients were divided into 4 groups. Group I included 27 patients (57.4%) who had systemic disease first and who subsequently developed an ocular lesion. Group II included 3 patients (6.3%) who had ocular inflammation first and who then subsequently developed systemic manifestations of WG. Group III included 3 patients (6.3%) who presented due to ocular symptoms but, on initial evaluation by us, were found to have occult systemic manifestations consistent with WG or biopsy evidence of WG. Group IV included 14 patients (30%) with ocular lesions and no history or presence of systemic disease at their last followup visit. Conclusion. Ocular inflammation can occur with or without obvious systemic manifestations of We. It may represent the first sign of WG that enables the knowledgeable physician to diagnose this potentially lethal disease. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Uveitis & Immunol Serv, Boston, MA USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Serv Immunol, 243 Charles St, Boston, MA 02114 USA. OI Sangwan, Virender/0000-0002-8229-4158 NR 31 TC 54 Z9 63 U1 0 U2 2 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2001 VL 28 IS 5 BP 1025 EP 1032 PG 8 WC Rheumatology SC Rheumatology GA 428XX UT WOS:000168487900018 PM 11361183 ER PT J AU Gill, TJ McIrvin, E Mair, SD Hawkins, RJ AF Gill, TJ McIrvin, E Mair, SD Hawkins, RJ TI Results of biceps tenotomy for treatment of pathology of the long head of the biceps brachii SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID TENDON AB Historically, the surgical treatment of bicipital pathology has been a variety of tenodesis techniques. The purpose of this study is to report the results of simple biceps tenotomy for the treatment of bicipital pathology. Thirty shoulders in 30 consecutive patients who had a simple arthroscopic biceps tendon release were reviewed. Data was collected according to the method of the American Shoulder and Elbow Surgeons (ASES) shoulder evaluation form. Outcome was assessed with the rating system of the ASES. The mean ASES shoulder score was 81.8. There was a significant reduction in pain and improvement in function after the procedure. The complication rate was 13.3%. Bicipital pathology is a significant cause of morbidity around the shoulder. The results of this study demonstrate that functional outcome as measured by the ASES scoring system can be very good with an arthroscopic biceps tendon release for the treatment of biceps tendon pathology. C1 Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. Steadman Hawkins Sports Med Fdn, Vail, CO USA. Univ Kentucky Sports Med, Kentucky Clin, Lexington, KY USA. RP Hawkins, RJ (reprint author), Steadman Hawkins Clin, 181 W Meadow Dr,Suite 400, Vail, CO 81647 USA. NR 12 TC 108 Z9 116 U1 0 U2 3 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 MAY-JUN PY 2001 VL 10 IS 3 BP 247 EP 249 DI 10.1067/mse.2001.114259 PG 3 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 450NA UT WOS:000169749000009 PM 11408906 ER PT J AU Shera, CA AF Shera, CA TI Frequency glides in click responses of the basilar membrane and auditory nerve: Their scaling behavior and origin in traveling-wave dispersion SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID COCHLEAR HAIR-CELLS; 3-DIMENSIONAL MODEL; ELECTRICAL RESONANCE; MOSSBAUER TECHNIQUE; CHINCHILLA COCHLEA; IMPULSE RESPONSES; FIBER RESPONSES; TIME-DOMAIN; STIMULI; FORM AB Frequency modulations (or glides), reported in impulse responses of both the auditory nerve and the basilar membrane, represent a change over time in the instantaneous frequency of oscillation of the response waveform, Although the near invariance of glides with stimulus intensity indicates that they are not the consequence of nonlinear or active processes in the inner ear, their origin has remained otherwise obscure. This paper combines theory with experimental data to explore the basic phenomenology of glides. When expressed in natural dimensionless form, glides are shown to have a universal form nearly independent of cochlear location for characteristic frequencies (CFs) above approximately 1.5 kHz (the ''scaling region''). In the apex of the cochlea, by contrast, glides appear to depend strongly on CF. In the scaling region, instantaneous-frequency trajectories are shown to be approximately equal to the "inverse group delays" of basilar-membrane transfer functions measured at the same locations. The inverse group delay, obtained by functionally inverting the transfer-function group-delay-versus-frequency curve, specifies the frequency component of a broadband stimulus expected to be driving the cochlear partition at the measurement point as a function of time. The approximate empirical equality of the two functions indicates that glides are closely related to cochlear traveling-wave dispersion and suggests that they originate primarily through the time dependence of the effective driving pressure force at the measurement location. Calculations in a one-dimensional cochlear model based on solution to the inverse problem in squirrel monkey [Zweig, J. Acoust. Sec. Am. 89, 1229-1254 (1991)] support this conclusion. In contrast to previous models for glides. which locate their origin in the differential build-up and decay of multiple micromechanical resonances local to each radial cross section of the organ of Corti, the model presented here identifies glides as the global consequence of the dispersive character of wave propagation in the cochlea. (C) 2001 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu FU NIDCD NIH HHS [R01 DC003687, R01 DC03687] NR 64 TC 37 Z9 37 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2001 VL 109 IS 5 BP 2023 EP 2034 DI 10.1121/1.1366372 PN 1 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 431AC UT WOS:000168608700026 PM 11386555 ER PT J AU Menaker, GM Chiang, JK Tabila, B Moy, RL AF Menaker, GM Chiang, JK Tabila, B Moy, RL TI Rapid HMB-45 staining in Mohs micrographic surgery for melanoma in situ and invasive melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SURGICAL MARGINS; CUTANEOUS MELANOMA; LOCAL RECURRENCE; NEVI; SECTIONS AB Background: Accurate interpretation of frozen sections in the treatment of melanoma by Mohs micrographic surgery may be difficult. Objective: Our purpose was to review the literature on the role of Mohs micrographic surgery in the treatment of melanoma and to demonstrate the added benefits of using rapid HMB-45 staining in Mohs micrographic surgery for the treatment of melanoma. Methods: Twenty cases of melanoma were included in our study. Histologic diagnosis in each case was made by means of excisional biopsy specimens and permanent sections. Mohs micrographic surgery was performed with 3-mm margins used for each stage. Each Mohs frozen section was stained with HMB-45. In addition, routine frozen sections stained with hematoxylin-eosin were also prepared for comparison. All tissues were also sent for permanent sections. These permanent sections were cut similarly to Mohs oriented sections because they were sectioned horizontally. Since they were serving as the standard, no staining with HMB-45 was performed on these permanent sections. Further stages with 3-mm margins were taken until tissues stained negative. Frozen sections were compared with permanent sections at each stage of resection. Results: Eleven of the 20 cases stained positive with HMB-45 antibody on the first Mohs stage. These results were consistent with findings on permanent sections. Ten of the 11 cases were cleared by the first stage. One of the 11 cases required 3 stages because margins were not cleared and the specimens stained HMB-45 positive. However, permanent sections in this case revealed no tumor in the second stage. Nine of 20 cases did not stain with HMB-45 on the first layer of Mohs excision. This was consistent with findings on permanent sections. Conclusion: HMB-45 staining serves as a rapid technique to aid in the interpretation of frozen sections during Mohs micrographic surgery in the treatment of melanoma. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Surg Unit, Boston, MA USA. Vanderbilt Univ, Dept Dermatol, Nashville, TN USA. Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Menaker, GM (reprint author), 15 Parkman St,WACC 481, Boston, MA 02114 USA. NR 18 TC 16 Z9 17 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2001 VL 44 IS 5 BP 833 EP 836 DI 10.1067/mjd.2001.111634 PG 4 WC Dermatology SC Dermatology GA 427VL UT WOS:000168426100016 PM 11312433 ER PT J AU Friedlander, AH Mahler, ME AF Friedlander, AH Mahler, ME TI Major depressive disorder - Psychopathology, medical management and dental implications SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; BURNING MOUTH SYNDROME; CHRONIC FACIAL-PAIN; PSYCHOSOCIAL FACTORS; TEMPOROMANDIBULAR PAIN; DYSFUNCTION SYNDROME; DRUG-INTERACTIONS; SUBSTANCE-ABUSE; INDUCED BRUXISM; LATE-LIFE AB Background. Major depressive disorder, or MDD, is a psychiatric illness in which mood, thoughts and behavioral patterns are impaired for long periods. The illness distresses the person and impairs his or her social functioning and quality of life. MDD is characterized by marked sadness or a loss of interest or pleasure in daily activities, and is accompanied by weight change, sleep disturbance, fatigue, difficulty concentrating, physical impairment and a high suicide rate. In 2000, the World Health Organization, or WHO, identified MDD as the fourth ranked cause of disability and premature death in the world. WHO projected that by 2020, MDD would rise in disease burden to be second only to ischemic heart disease. The disorder is common in the United States, with a life-time prevalence rate of 17 percent and a recurrence rate of more than 50 percent. Conclusions. MDD may be associated with extensive dental disease, and people may seek dental treatment before becoming aware of their psychiatric illness. MDD frequently is associated with a disinterest in performing appropriate oral hygiene techniques, a cariogenic diet, diminished salivary flow, rampant dental caries, advanced periodontal disease and oral dysesthesias. Many medications used-to treat the disease magnify the xerostomia-and increase the incidence of dental disease. Appropriate dental management requires a vigorous dental education program, the use of saliva substitutes and anticaries agents containing fluoride, and special precautions when prescribing or administering analgesics and local anesthetics. Clinical Implications. Dentists cognizant of these signs and symptoms have occult MDD. After confirmation of the diagnosis and institution of treatment by a mental health practitioner, dentists usually can provide a full range of services that may enhance patients' self-esteem and contribute to the psychotherapeutic aspect of management. C1 Vet Affairs Greater Los Angeles Healthcare Syst 1, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Hosp Dent Serv, Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst 1, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 74 TC 30 Z9 32 U1 0 U2 4 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAY PY 2001 VL 132 IS 5 BP 629 EP 638 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 431UT UT WOS:000168650700018 PM 11367967 ER PT J AU Espino, DV Lichtenstein, MJ Palmer, RF Hazuda, HP AF Espino, DV Lichtenstein, MJ Palmer, RF Hazuda, HP TI Ethnic differences in Mini-Mental State Examination (MMSE) scores: Where you live makes a difference SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE Mexican Americans; Mini-Mental State Examination (MMSE); ethnic differences ID MEXICAN-AMERICANS; SOCIOCULTURAL STATUS; DEMENTIA; POPULATION; DEPRESSION; ASSOCIATION; VALIDATION; EDUCATION; VERSION; HEALTH AB OBJECTIVES: To examine differences in correlates of the Mini-Mental State Examination (MMSE) in a population-based sample of older Mexican Americans and European Americans and to provide empirical validation of the MMSE as an indicator of cognitive impairment in survey research in older Mexican Americans by comparing MMSE classification against performance on timed tasks with varying levels of cognitive demand. DESIGN: A population-based cross-sectional study. SETTING: Trained bilingual staff administered the MMSE as part of the San Antonio Longitudinal Study of Aging (SALSA) home-based assessment battery. PARTICIPANTS: 827 community-dwelling Mexican Americans and European Americans, 65 and older, residing in three socioeconomically and culturally distinct neighborhoods (barrio, transitional, suburban). MEASUREMENTS: The MMSE was compared against a variety of demographic, biomedical, and sociocultural variables ascertained by self-report and against performance-based measures of functional tasks representing varying levels of cognitive demand (Structured Assessment of Independent Living Skills (SAILS) subscales for food manipulation and money management). RESULTS: Mexican Americans were 2.2 times more likely than European Americans to have MMSE scores < 24, Multiple logistic regression analysis revealed that neighborhood was an independent predictor of low MMSE scores in Mexican Americans, with the relationship between ethnic group and MMSE explained by neighborhood. After adjusting for neighborhood type, no differences were noted between Mexican Americans and European Americans. Independent of other factors examined, low education was associated with low MMSE scores in both Mexican Americans and European Americans. Mexican Americans with MMSE scores < 24 took significantly longer to complete four out of: five performance-based food manipulation tasks and all three money management tasks. CONCLUSIONS: Neighborhood typo was a predictor of cognitive impairment. Education affected MMSE scores similarly in both ethnic groups. MMSE scores < 24, indicative of cognitive impairment, were uniformly associated with functional impairment in both the Mexican Americans and European Americans. Among older Mexican Americans, MMSE-classified cognitive impairment was significantly associated with poorer performance on timed tasks with varying levels of cognitive demand independent of ether correlates. A similar pattern of association was observed in European Americans. Thus, the MMSE appears to be a valid indicator of cognitive impairment in survey research in both older Mexican Americans and European Americans. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Family Practice, Div Commun Geriatr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Med, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX USA. RP Hazuda, HP (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Epidemiol, 7703 Floyd Curl Dr,MC 7873, San Antonio, TX 78229 USA. FU NCRR NIH HHS [MO1-RR-01346]; NIA NIH HHS [1-ROI-AG10444] NR 38 TC 74 Z9 76 U1 2 U2 13 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 MAY PY 2001 VL 49 IS 5 BP 538 EP 548 DI 10.1046/j.1532-5415.2001.49111.x PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 436DV UT WOS:000168922000005 PM 11380745 ER PT J AU Hourigan, LA Burstow, DJ Pohlner, P Clarke, BE Donnelly, JE AF Hourigan, LA Burstow, DJ Pohlner, P Clarke, BE Donnelly, JE TI Transesophageal echocardiographic abnormalities in a case of cardiac sarcoidosis SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Editorial Material ID SYSTEMIC SARCOIDOSIS AB Sarcoidosis is a granulomatous disease that may involve multiple organ systems, including the heart. Manifestations include atrial and ventricular arrhythmias, conduction abnormalities, congestive cardiac failure, pericarditis, and sudden death. Whereas cardiac involvement is a relatively common finding at autopsy, antemortem diagnosis is often missed because the clinical manifestations are nonspecific, and die sensitivity and specificity of investigations are low. We report a case of a 62-year-old woman who had clinically significant cardiac sarcoidosis associated with echocardiographic abnormalities that had not been reported previously in association with this condition. C1 Prince Charles Hosp, Dept Cardiol, Brisbane, Qld 4032, Australia. Prince Charles Hosp, Dept Cardiothorac Surg, Brisbane, Qld 4032, Australia. Prince Charles Hosp, Dept Pathol, Brisbane, Qld 4032, Australia. RP Hourigan, LA (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Grey Bldg,Room 645,55 Fruit St, Boston, MA 02114 USA. RI Burstow, Darryl/C-9434-2011 NR 11 TC 6 Z9 6 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD MAY PY 2001 VL 14 IS 5 BP 399 EP 402 DI 10.1067/mje.2001.110785 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 432QP UT WOS:000168707400011 PM 11337687 ER EF