FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Marino, M
   Chiovato, L
   Lisi, S
   Pinchera, A
   McCluskey, RT
AF Marino, M
   Chiovato, L
   Lisi, S
   Pinchera, A
   McCluskey, RT
TI Binding of the low density lipoprotein receptor-associated protein (RAP)
   to thyroglobulin (Tg): Putative role of RAP in the Tg secretory pathway
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID THYROID-HORMONE RELEASE; ENDOPLASMIC-RETICULUM; ENDOCYTIC RECEPTOR;
   MEGALIN GP330; CELLS; TRANSCYTOSIS; FAMILY; BIP
AB The 39-44 kDa protein known as the receptor-associated protein binds to members of the low density lipoprotein receptor family and is found within cells that express these receptors. The receptor-associated protein has been shown to prevent premature binding of ligands to the receptors in the endoplasmic reticulum and to promote proper folding and transport of the receptors in the secretory pathway. In the thyroid, megalin (a low-density lipoprotein receptor family member) serves as an endocytic receptor for thyroglobulin. Here we present evidence that the receptor-associated protein can bind to thyroglobulin, which suggests a novel function of the receptor-associated protein, namely binding of certain megalin ligands possibly during the biosynthetic pathway.
   In solid-phase assays thyroglobulin was shown to bind to the receptor-associated protein with moderately high affinity (mean between Kd and K-i = 39.8 nM), in a calcium-dependent and saturable manner. The receptor-associated protein also bound to a native carboxyl-terminal 230-kDa thyroglobulin polypeptide, which markedly reduced binding of intact thyroglobulin to the receptor-associated protein, indicating that the receptor-associated protein binding sites of thyroglobulin are located in the carboxyl-terminal portion of the molecule. In addition to thyroglobulin, the receptor-associated protein specifically bound to another megalin ligand, namely lipoprotein lipase. Because lipoprotein lipase markedly reduced receptor-associated protein binding to thyroglobulin, we concluded that the receptor-associated protein uses the same binding site/s to bind to thyroglobulin and lipoprotein lipase. Evidence of thyroglobulin binding to the receptor-associated protein was also obtained in vivo and in cultured thyroid cells. Thus, anti-receptor-associated protein antibodies precipitated intact thyroglobulin from extracts prepared from rat thyroids and cultured thyroid cells (FRTL-5 cells). Chase experiments after inhibition of protein synthesis in FRTL-5 cells showed that thyroglobulin interacts with the receptor-associated protein shortly after the beginning of thyroglobulin biosynthesis.
C1 Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Res Lab, Boston, MA 02129 USA.
RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy.
FU NIDDK NIH HHS [DK 46301]
NR 26
TC 10
Z9 10
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 OCT
PY 2001
VL 15
IS 10
BP 1829
EP 1837
DI 10.1210/me.15.10.1829
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 477DL
UT WOS:000171267800016
PM 11579214
ER

PT J
AU Wright, DL
   Jones, EL
   Mayer, JF
   Oehninger, S
   Gibbons, WE
   Lanzendorf, SE
AF Wright, DL
   Jones, EL
   Mayer, JF
   Oehninger, S
   Gibbons, WE
   Lanzendorf, SE
TI Characterization of telomerase activity in the human oocyte and
   preimplantation embryo
SO MOLECULAR HUMAN REPRODUCTION
LA English
DT Article; Proceedings Paper
CT 56th Annual Meeting of the American-Society-for-Reproductive-Medicine
CY OCT 21-26, 2000
CL SAN DIEGO, CALIFORNIA
SP Amer Soc Reprod Med
DE embryo; human; oocyte; telomerase; TRAP
ID STEM-CELL LINES; IN-VITRO; IMMORTAL CELLS; HEPATOCELLULAR-CARCINOMA;
   CATALYTIC SUBUNIT; MESSENGER-RNA; EXPRESSION; TISSUES; DIAGNOSIS;
   PREGNANCY
AB Telomerase, a ribonucleoprotein, has been described as an essential component of highly proliferative cells as it stabilizes the telomeres and avoids cellular senescence. The objective of this study was to modify the polymerase chain reaction-based telomeric repeat amplification protocol to detect telomerase activity in the single cell and to characterize the activity expressed in the human oocyte through to the blastocyst stage embryo. A comparative evaluation of telomerase activity and developmental stage was conducted using discarded or donated human oocytes and embryos. Telomerase activity was detected in all developmental stages evaluated from immature oocytes through to blastocyst stage embryos. Immature oocytes and blastocysts had similar levels of telomerase activity; however, both groups had significantly (P < 0.05) higher activity than zygote through to pre-morula stage embryos. Seventy-five thawed zygotes were cultured to day 3, biopsied by removing 1-2 cells, and the biopsied embryos were cultured to blastocyst stage. There was no difference (P < 0.05) in telomerase activity between cells biopsied from embryos that reached the blastocyst stage and cells from those that arrested in growth. This study has shown that human oocytes through to blastocyst stage embryos express telomerase activity, but that the level of telomerase activity in biopsied blastomeres, of the day 3 cleavage stage embryo, is not predictive of embryonic growth potential.
C1 Eastern Virginia Med Sch, Jones Inst Reprod Med, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Norfolk, VA USA.
   Eastern Virginia Med Sch, Jones Inst Reprod Med, Technol Dev Ctr, Norfolk, VA USA.
RP Wright, DL (reprint author), Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Vincent Mem Obstet & Gynecol Serv, 55 Fruit St VBK 225, Boston, MA 02114 USA.
NR 45
TC 39
Z9 41
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1360-9947
J9 MOL HUM REPROD
JI Mol. Hum. Reprod.
PD OCT
PY 2001
VL 7
IS 10
BP 947
EP 955
DI 10.1093/molehr/7.10.947
PG 9
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA 480RE
UT WOS:000171475200005
PM 11574663
ER

PT J
AU Gryllos, L
   Cywes, C
   Shearer, MH
   Cary, M
   Kennedy, RC
   Wessels, MR
AF Gryllos, L
   Cywes, C
   Shearer, MH
   Cary, M
   Kennedy, RC
   Wessels, MR
TI Regulation of capsule gene expression by group A Streptococcus during
   pharyngeal colonization and invasive infection
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID HYALURONIC-ACID CAPSULE; GROUP-A STREPTOCOCCUS; GREEN FLUORESCENT
   PROTEIN; THROAT COLONIZATION; VIRULENCE FACTORS; HOST-CELLS; IN-VITRO;
   PYOGENES; KERATINOCYTES; OPERON
AB Capsular polysaccharide production by group A Streptococcus (GAS) is controlled by transcription of the has operon that encodes the enzymes uniquely required for synthesis of the hyaluronic acid polysaccharide. To investigate the regulation of capsule gene expression during infection, we developed a reporter strain of GAS in which the has operon promoter directed transcription of green fluorescent protein (GFP). Gfp expression was triggered within minutes after introduction of the reporter strain into the peritoneal cavity of mice, as evidenced by the recovery of highly fluorescent GAS from the peritoneum 1 h after challenge. Capsule gene expression was also stimulated in the bloodstream of infected mice, as intensely fluorescent bacteria were observed in blood samples collected after either intraperitoneal or intravenous challenge. Using a similar approach, we also observed rapid induction of capsule gene expression in bacteria inoculated into the pharynx of baboons. Compared to the inoculum, increased green fluorescence was recorded in bacteria recovered from throat swabs collected 1 h after inoculation in all five animals studied. We conclude that introduction of GAS into the pharynx or into deep tissues results in rapid induction of has operon expression, a critical adaptive response that enhances GAS survival in the infected host.
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA.
   Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA.
   Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73190 USA.
   Harvard Univ, Childrens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA.
RP Wessels, MR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA.
NR 38
TC 7
Z9 8
U1 1
U2 1
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 OCT
PY 2001
VL 42
IS 1
BP 61
EP 74
PG 14
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 482PY
UT WOS:000171585500007
ER

PT J
AU Ibebunjo, C
   Martyn, J
AF Ibebunjo, C
   Martyn, J
TI Disparate dysfunction of skeletal muscles located near and distant from
   burn site in the rat
SO MUSCLE & NERVE
LA English
DT Article; Proceedings Paper
CT 30th Annual Meeting of the American-Burn-Association
CY MAR 18-21, 1998
CL CHICAGO, ILLINOIS
SP Amer Burn Assoc
DE contractility; gene expression; membrane acetylcholine receptors;
   thermal injury; tibialis anterior muscle
ID CONGENITAL MYASTHENIC SYNDROMES; ACETYLCHOLINE-RECEPTOR;
   NEUROMUSCULAR-JUNCTION; D-TUBOCURARINE; INJURY; EXPRESSION; MEMBRANE;
   ATROPHY; SUBUNIT; IMMOBILIZATION
AB This study tested the hypotheses that burn-induced change in muscle function varies at sites local and distant from burn and is related to changes in expression of acetylcholine receptors (AChRs) and muscle mass. In anesthetized rats, similar to4% burn was inflicted over the tibialis anterior muscle of one limb. The contralateral leg served as control. In another study, a similar to 45% body surface area burn was produced on the trunk; controls were body sham-burned rats. The evoked twitch tensions of tibialis anterior muscles in both legs were measured together with AChR proteins and their transcripts. Compared with the contralateral leg, absolute tensions in the burned leg declined at days 1, 4, and 7 without loss of muscle mass so that tension per unit wet muscle mass (specific tension) decreased; at day 14, the tension decreased with muscle atrophy so that specific tension was unchanged. Membrane AChRs and/or the immature subunit transcript, AChR gamma messenger ribonucleic acid (mRNA) increased at days 4, 7, and 14, and both were inversely related to evoked tension (r = .43, P < .01 and r = .01, P < .0001, respectively). There was a direct correlation between AChR and AChR gamma mRNA (r = .82, P < .001), suggesting that the upregulated AChRs may contain the immature gamma -subunit isoform. After similar to 45% body burn, AChRs and mRNA did not change and the evoked tensions did not decline, but there was relative loss of muscle mass at days 7 and 14 so that specific tension increased. Burn trauma initially causes weakness of muscles directly under the burn, and this weakness may be partially related to increased expression of immature AChRs and later to muscle atrophy. (C) 2001 John Wiley & Sons, Inc.
C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
   Shriners Burns Hosp, Anesthesia Serv, Boston, MA USA.
RP Martyn, J (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Fruit St, Boston, MA 02114 USA.
FU NIGMS NIH HHS [GM55082-05, GM61411-02, GM31569-18]
NR 39
TC 22
Z9 25
U1 1
U2 1
PU JOHN WILEY & SONS INC
PI NEW YORK
PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0148-639X
J9 MUSCLE NERVE
JI Muscle Nerve
PD OCT
PY 2001
VL 24
IS 10
BP 1283
EP 1294
DI 10.1002/mus.1146
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 477PR
UT WOS:000171293900004
PM 11562907
ER

PT J
AU Randow, F
   Seed, B
AF Randow, F
   Seed, B
TI Endoplasmic reticulum chaperone gp96 is required for innate immunity but
   not cell viability
SO NATURE CELL BIOLOGY
LA English
DT Article
ID HEAT-SHOCK-PROTEIN; TOLL-LIKE RECEPTOR-4; HSP90 MOLECULAR CHAPERONE;
   IN-VIVO FUNCTION; CRYSTAL-STRUCTURE; ATP BINDING; TLR4;
   LIPOPOLYSACCHARIDE; HYDROLYSIS; MUTATIONS
AB Chaperone proteins are thought to promote the correct folding and assembly of newly synthesized proteins and to facilitate restoration of the folded state under environmental conditions that favour protein denaturation. They are among the most ubiquitous and highly conserved of all proteins. The eukaryotic endoplasmic reticulum (ER) chaperone gp96 in particular has long been thought to be indispensable for cell survival. Here we report that a screen for genes required for the immune response to bacterial endotoxins has identified a B-cell line deficient in gp96. Absence of gp96 is compatible with cellular survival even under stress conditions and causes a defect in the formation of only a small subset of cell surface receptors. Toll-like receptors are retained intracellularly in the absence of gp96, explaining the unresponsiveness of the mutant to microbial stimuli.
C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA.
NR 32
TC 214
Z9 216
U1 0
U2 6
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD OCT
PY 2001
VL 3
IS 10
BP 891
EP 896
DI 10.1038/ncb1001-891
PG 6
WC Cell Biology
SC Cell Biology
GA 479GJ
UT WOS:000171396400013
PM 11584270
ER

PT J
AU Snapper, SB
   Takeshima, F
   Anton, I
   Liu, CH
   Thomas, SM
   Nguyen, D
   Dudley, D
   Fraser, H
   Purich, D
   Lopez-Ilasaca, M
   Klein, C
   Davidson, L
   Bronson, R
   Mulligan, RC
   Southwick, F
   Geha, R
   Goldberg, MB
   Rosen, FS
   Hartwig, JH
   Alt, FW
AF Snapper, SB
   Takeshima, F
   Anton, I
   Liu, CH
   Thomas, SM
   Nguyen, D
   Dudley, D
   Fraser, H
   Purich, D
   Lopez-Ilasaca, M
   Klein, C
   Davidson, L
   Bronson, R
   Mulligan, RC
   Southwick, F
   Geha, R
   Goldberg, MB
   Rosen, FS
   Hartwig, JH
   Alt, FW
TI N-WASP deficiency reveals distinct pathways for cell surface projections
   and microbial actin-based motility
SO NATURE CELL BIOLOGY
LA English
DT Article
ID WISKOTT-ALDRICH-SYNDROME; ARP2/3 COMPLEX; SYNDROME PROTEIN;
   SHIGELLA-FLEXNERI; LISTERIA-MONOCYTOGENES; DEPOLYMERIZING PROTEIN;
   FILOPODIUM FORMATION; WASP/SCAR PROTEINS; FAMILY PROTEIN; POLYMERIZATION
AB The Wiskott-Aldrich syndrome protein (WASP) family of molecules integrates upstream signalling events with changes in the actin cytoskeleton. N-WASP has been implicated both in the formation of cell-surface projections (filopodia) required for cell movement and in the actin-based motility of intracellular pathogens. To examine N-WASP function we have used homologous recombination to inactivate the gene encoding murine N-WASP. Whereas N-WASP-deficient embryos survive beyond gastrulation and initiate organogenesis, they have marked developmental delay and die before embryonic day 12. N-WASP is not required for the actin-based movement of the intracellular pathogen Listeria but is absolutely required for the motility of Shigella and vaccinia virus. Despite these distinct defects in bacterial and viral motility, N-WASP-deficient fibroblasts spread by using lamellipodia and can protrude filopodia. These results imply a crucial and non-redundant role for N-WASP in murine embryogenesis and in the actin-based motility of certain pathogens but not in the general formation of actin-containing structures.
C1 Ctr Blood Res, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA.
   Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
   Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
   Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA.
   Beth Israel Deaconess Hosp, Div Hematol, Boston, MA 02215 USA.
   Univ Florida, Coll Med, Dept Infect Dis, Gainesville, FL 32601 USA.
   Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Snapper, SB (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA.
RI Anton, Ines/G-6090-2015
FU NIAID NIH HHS [R01 AI023262, R01 AI034276]
NR 50
TC 227
Z9 229
U1 0
U2 4
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD OCT
PY 2001
VL 3
IS 10
BP 897
EP 904
DI 10.1038/ncb1001-897
PG 8
WC Cell Biology
SC Cell Biology
GA 479GJ
UT WOS:000171396400014
PM 11584271
ER

PT J
AU Puglielli, L
   Konopka, G
   Pack-Chung, E
   Ingano, LAM
   Berezovska, O
   Hyman, BT
   Chang, TY
   Tanzi, RE
   Kovacs, DM
AF Puglielli, L
   Konopka, G
   Pack-Chung, E
   Ingano, LAM
   Berezovska, O
   Hyman, BT
   Chang, TY
   Tanzi, RE
   Kovacs, DM
TI Acyl-coenzyme A : cholesterol acyltransferase modulates the generation
   of the amyloid beta-peptide
SO NATURE CELL BIOLOGY
LA English
DT Article
ID HAMSTER OVARY CELLS; PRECURSOR PROTEIN; ACAT INHIBITOR;
   SIGNAL-TRANSDUCTION; ALZHEIMERS-DISEASE; PLASMA-MEMBRANE; SITE-2
   PROTEASE; LIVER; ESTERIFICATION; TRAFFICKING
AB The pathogenic event common to all forms of Alzheimer's disease is the abnormal accumulation of the amyloid beta -peptide (A beta). Here we provide strong evidence that intracellular cholesterol compartmentation modulates the generation of A beta. Using genetic, biochemical and metabolic approaches, we found that cholesteryl-ester levels are directly correlated with A beta production. Acyl-coenzyme A:cholesterol acyltransferase (ACAT), the enzyme that catalyses the formation of cholesteryl esters, modulates the generation of A beta through the tight control of the equilibrium between free cholesterol and cholesteryl esters. We also show that pharmacological inhibitors of ACAT, developed for the treatment of atherosclerosis, are potent modulators of A beta generation, indicating their potential for use in the treatment of Alzheimer's disease.
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Alzheimer Res Unit, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA.
   Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA.
RP Kovacs, DM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Bldg 114,16th St, Charlestown, MA 02129 USA.
OI Chang, Ta-Yuan/0000-0002-3249-0468
NR 50
TC 281
Z9 292
U1 0
U2 5
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD OCT
PY 2001
VL 3
IS 10
BP 905
EP 912
DI 10.1038/ncb1001-905
PG 8
WC Cell Biology
SC Cell Biology
GA 479GJ
UT WOS:000171396400015
PM 11584272
ER

PT J
AU Tsukiyama-Kohara, K
   Poulin, F
   Kohara, M
   DeMaria, CT
   Cheng, A
   Wu, ZD
   Gingras, AC
   Katsume, A
   Elchebly, M
   Spiegelman, BM
   Harper, ME
   Tremblay, ML
   Sonenberg, N
AF Tsukiyama-Kohara, K
   Poulin, F
   Kohara, M
   DeMaria, CT
   Cheng, A
   Wu, ZD
   Gingras, AC
   Katsume, A
   Elchebly, M
   Spiegelman, BM
   Harper, ME
   Tremblay, ML
   Sonenberg, N
TI Adipose tissue reduction in mice lacking the translational inhibitor
   4E-BP1
SO NATURE MEDICINE
LA English
DT Article
ID MITOCHONDRIAL UNCOUPLING PROTEIN; ADAPTIVE THERMOGENESIS; 4E-BINDING
   PROTEIN-1; BODY-WEIGHT; WHITE FAT; PHAS-I; GENE; OBESITY; EXPRESSION;
   PHOSPHORYLATION
AB All nuclear-encoded mRNAs contain a 5' cap structure (m(7)GpppN, where N is any nucleotide), which is recognized by the eukaryotic translation initiation factor 4E (eIF4E) subunit of the eIF4F complex. The elF4E-binding proteins constitute a family of three polypeptides that reversibly repress cap-dependent translation by binding to eIF4E, thus preventing the formation of the eIF4F complex. We investigated the biological function of 4E-BP1 by disrupting its gene (Eif4ebp1) in the mouse. Eif4ebp1(-/-) mice manifest markedly smaller white fat pads than wild-type animals, and knockout males display an increase in metabolic rate. The males' white adipose tissue contains cells that exhibit the distinctive multilocular appearance of brown adipocytes, and expresses the uncoupling protein 1 (UCP1), a specific marker of brown fat. Consistent with these observations, translation of the peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC1), a transcriptional co-activator implicated in mitochondrial biogenesis and adaptive thermogenesis, is increased in white adipose tissue of Eif4ebp1(-/-) mice. These findings demonstrate that 4E-BP1 is a novel regulator of adipogenesis and metabolism in mammals.
C1 McGill Univ, Dept Biochem, Montreal, PQ, Canada.
   McGill Univ, Ctr Canc, Montreal, PQ H3G 1Y6, Canada.
   Tokyo Metropolitan Inst Med Sci, Dept Microbiol & Cell Biol, Tokyo 113, Japan.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Chugai Pharmaceut Co Ltd, Fuji Gotemba Res Labs, Shizuoka, Japan.
   Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada.
   Univ Tokyo, Inst Med Sci, Tokyo, Japan.
RP Sonenberg, N (reprint author), McGill Univ, Dept Biochem, Montreal, PQ, Canada.
RI Gingras, Anne-Claude/E-9982-2010; Cheng, Alan/M-9319-2013; 
OI Gingras, Anne-Claude/0000-0002-6090-4437; Cheng,
   Alan/0000-0001-7897-4751; Harper, Mary-Ellen/0000-0003-3864-5886
NR 29
TC 240
Z9 246
U1 1
U2 9
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 OCT
PY 2001
VL 7
IS 10
BP 1128
EP 1132
DI 10.1038/nm1001-1128
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 481NA
UT WOS:000171524500034
PM 11590436
ER

PT J
AU Lu, QR
   Cai, L
   Rowitch, D
   Cepko, CL
   Stiles, CD
AF Lu, QR
   Cai, L
   Rowitch, D
   Cepko, CL
   Stiles, CD
TI Ectopic expression of Olig1 promotes oligodendrocyte formation and
   reduces neuronal survival in developing mouse cortex
SO NATURE NEUROSCIENCE
LA English
DT Article
ID DIFFERENTIATION; PROTEINS; GENES
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA.
RP Cepko, CL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA.
NR 15
TC 89
Z9 94
U1 2
U2 6
PU NATURE AMERICA INC
PI NEW YORK
PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD OCT
PY 2001
VL 4
IS 10
BP 973
EP 974
DI 10.1038/nn718
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA 478CR
UT WOS:000171325800007
PM 11574831
ER

PT J
AU Watson, FL
   Heerssen, HM
   Bhattacharyya, A
   Klesse, L
   Lin, MZ
   Segal, RA
AF Watson, FL
   Heerssen, HM
   Bhattacharyya, A
   Klesse, L
   Lin, MZ
   Segal, RA
TI Neurotrophins use the Erk5 pathway to mediate a retrograde survival
   response
SO NATURE NEUROSCIENCE
LA English
DT Article
ID TRANSCRIPTION FACTOR; SYMPATHETIC NEURONS; CELL-SURVIVAL; CREB
   PHOSPHORYLATION; SIGNALING PATHWAY; NERVOUS-SYSTEM; GROWTH-FACTOR; NGF;
   KINASE; RAS
AB Growth factors synthesized and released by target tissues promote survival and differentiation of innervating neurons. This retrograde signal begins when growth factors bind receptors at nerve terminals. Activated receptors are then endocytosed and transported through the axon to the cell body. Here we show that the mitogen-activated protein kinase (MAPK) signaling pathways used by neurotrophins during retrograde signaling differ from those used following direct stimulation of the cell soma. During retrograde signaling, endocytosed neurotrophin receptors (Trks) activate the extracellular signal-related protein kinase S (Erk5) pathway, leading to nuclear translocation of Erk5, phosphorylation of CREB, and enhanced neuronal survival. In contrast, Erk1/2, which mediates nuclear responses following direct cell body stimulation, does not transmit a retrograde signal. Thus, the Erk5 pathway has a unique function in retrograde signaling. Differential activation of distinct MAPK pathways may enable an individual growth factor to relay information that specifies the location and the nature of stimulation.
C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX 75390 USA.
   Childrens Hosp, Div Neurosci, Boston, MA 02115 USA.
RP Segal, RA (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA.
FU NINDS NIH HHS [NS35148]
NR 38
TC 305
Z9 313
U1 1
U2 10
PU NATURE AMERICA INC
PI NEW YORK
PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD OCT
PY 2001
VL 4
IS 10
BP 981
EP 988
DI 10.1038/nn720
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 478CR
UT WOS:000171325800011
PM 11544482
ER

PT J
AU Nagler-Anderson, C
AF Nagler-Anderson, C
TI Man the barrier! Strategic defences in the intestinal mucosa
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID INFLAMMATORY-BOWEL-DISEASE; THYMUS-EXPRESSED CHEMOKINE; TOLL-LIKE
   RECEPTORS; FOLLICLE-ASSOCIATED EPITHELIUM; HEAT-LABILE ENTEROTOXIN;
   PATCH DENDRITIC CELLS; PEYERS PATCH; IN-VIVO; T-CELLS; IMMUNE-SYSTEM
AB Immunologists typically study the immune responses induced in the spleen or peripheral lymph nodes after parenteral immunization with antigen and poorly defined experimental adjuvants. However, most antigens enter the body through mucosal surfaces. It is now clear that the microenvironment in these mucosal barriers has a marked influence on the immune response that ultimately ensues. Nowhere is the microenvironment more influential than in the gut-associated lymphoid tissue (GALT). The GALT must constantly distinguish harmless antigens that are present in food or on commensal bacteria from pathogenic assault by microbes. It is perhaps not surprising, then, that the GALT contains more lymphocytes than all of the secondary lymphoid organs combined.
C1 Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Nagler-Anderson, C (reprint author), Massachusetts Gen Hosp, Dept Pediat, Bldg 114,16th St,Room 3600, Charlestown, MA 02129 USA.
NR 98
TC 202
Z9 210
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD OCT
PY 2001
VL 1
IS 1
BP 59
EP 67
DI 10.1038/35095573
PG 9
WC Immunology
SC Immunology
GA 635KK
UT WOS:000180397900024
PM 11905815
ER

PT J
AU Akbarian, S
   Chen, RZ
   Gribnau, J
   Rasmussen, TP
   Fong, HF
   Jaenisch, R
   Jones, EG
AF Akbarian, S
   Chen, RZ
   Gribnau, J
   Rasmussen, TP
   Fong, HF
   Jaenisch, R
   Jones, EG
TI Expression pattern of the Rett syndrome gene MeCP2 in primate prefrontal
   cortex
SO NEUROBIOLOGY OF DISEASE
LA English
DT Article
DE transcriptional repression; gene silencing; DNA methylation; Old World
   monkey; Macaca mulatta; frontal lobe; autism
ID CPG-BINDING PROTEIN-2; HISTONE MACROH2A1; MUTATIONS; NEURONS; BRAIN;
   METHYLATION; CHROMOSOME; NEOCORTEX; CELLS
AB Dysfunction of the prefrontal cortex may contribute to the autistic features and mental retardation of Rett syndrome, a neuropsychiatric condition caused by mutations of the gene encoding methyl-CpG-binding protein 2 (MeCP2). Because nothing is known about the expression of MeCP2 and other chromatin-associated factors in primate brain, we studied in monkey prefrontal cortex and murine cerebral cortex expression patterns of MeCP2 and of macrohistone H2A (MacroH2A), which like MeCP2 is associated with transcriptionally silent chromatin. In both species, MeCP2 and MacroH2A appeared to be ubiquitously expressed by cortical neurons, including projection neurons and GABAergic interneurons. In the adult monkey, MeCP2 expression was robust throughout all layers of the prefrontal cortex but it was limited in fetal monkeys at embryonic day 110 to the deeper cortical layers and the subplate. These results suggest that MeCP2 may be important for neuronal maintenance in the developing and in the mature primate prefrontal cortex, consistent with the previously reported phenotype of MeCP2-null mutant mice. (C) 2001 Academic Press.
C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
   MIT, Dept Biol, Cambridge, MA 02142 USA.
   Univ Calif Davis, Ctr Neurosci, Livermore, CA 95616 USA.
RP Akbarian, S (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
FU NCI NIH HHS [CA 44339]; NINDS NIH HHS [NS21377]
NR 27
TC 73
Z9 76
U1 2
U2 4
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 OCT
PY 2001
VL 8
IS 5
BP 784
EP 791
DI 10.1006/nbdi.2001.0420
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 486QH
UT WOS:000171828100005
PM 11592848
ER

PT J
AU Purdon, PL
   Solo, V
   Weisskoff, RM
   Brown, EN
AF Purdon, PL
   Solo, V
   Weisskoff, RM
   Brown, EN
TI Locally regularized spatiotemporal modeling and model comparison for
   functional MRI
SO NEUROIMAGE
LA English
DT Article
DE functional MRI; regularization; spatiotemporal modeling; system
   identification; model comparison
ID TIME-SERIES ANALYSIS; IMAGING DATA; FMRI; ACTIVATION; DOMAIN; NOISE
AB In this work we treat fMRI data analysis as a spatiotemporal system identification problem and address issues of model formulation, estimation, and model comparison. We present a new model that includes a physiologically based hemodynamic response and an empirically derived low-frequency noise model. We introduce an estimation method employing spatial regularization that improves the precision of spatially varying noise estimates. We call the algorithm locally regularized spatiotemporal (LRST) modeling. We develop, anew model selection criterion and compare our model to the SPM-GLM method. Our findings suggest that our method offers a better approach to identifying appropriate statistical models for fMRI studies. (C) 2001 Academic Press.
C1 Massachusetts Gen Hosp NMR Ctr, Charlestown, MA USA.
   Univ New S Wales, Sch Elect Engn, Sydney, NSW, Australia.
   Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
   Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Purdon, PL (reprint author), Massachusetts Gen Hosp NMR Ctr, Charlestown, MA USA.
FU NCRR NIH HHS [P41 RR14075]; NIMH NIH HHS [KO2 MH61637]
NR 41
TC 82
Z9 84
U1 2
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 OCT
PY 2001
VL 14
IS 4
BP 912
EP 923
DI 10.1006/nimg.2001.0870
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
   Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 478EK
UT WOS:000171329800013
PM 11554810
ER

PT J
AU Ali, SO
   Denicoff, KD
   Altshuler, LL
   Hauser, P
   Li, XM
   Conrad, AJ
   Smith-Jackson, EE
   Leverich, GS
   Post, RM
AF Ali, SO
   Denicoff, KD
   Altshuler, LL
   Hauser, P
   Li, XM
   Conrad, AJ
   Smith-Jackson, EE
   Leverich, GS
   Post, RM
TI Relationship between prior course of illness and neuroanatomic
   structures in bipolar disorder - A preliminary study
SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY
LA English
DT Article; Proceedings Paper
CT 151st Annual Meeting of the American-Psychiatric-Association
CY MAY 30-JUN 05, 1998
CL TORONTO, CANADA
SP Amer Psychiat Assoc
ID MAJOR DEPRESSION; MOOD DISORDERS; BRAIN CHANGES; MRI; SCHIZOPHRENIA;
   PERFORMANCE; REDUCTION; VOLUME
AB Objective: In this preliminary study, we examined the relationships between prior course and severity of illness and size of the hippocampus, temporal lobes, and third and lateral ventricles in patients with bipolar disorder. Background: The few studies that have investigated relationships between course of illness measures and neuroanatomic structures in patients with bipolar disorder found divergent results. Method: Twenty-six outpatients, who met Diagnostic and Statistical Manual, Third Edition - Revised (DSM-III-R) criteria for bipolar disorder, received a magnetic resonance imaging (MRI) scan. from which volumes of the temporal lobes. hippocampi, third ventricle, and areas of the lateral ventricles were calculated. Prior course of illness variables were determined using the NIMH Life-Chart Method and were correlated to the volumetric measures of neuroanatomic structures using multiple regression analyses. Results: A longer duration of illness was paradoxically associated with a larger left temporal lobe volume whether patients with a history of substance abuse were removed from the analyses. Conclusions: Additional studies are needed to both replicate and further examine the association of prior course of illness and larger hippocampal and ventricular volumes in bipolar disorder.
C1 NIMH, Biol Psychiat Branch, NIH, Psychol Sect, Bethesda, MD 20892 USA.
   Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
   W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA.
   Portland Vet Affairs Med Ctr, Dept Psychiat, Portland, OR USA.
   Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA.
   Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA.
   Natl Inst Genet, Los Angeles, CA USA.
RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Psychol Sect, 9000 Rockville Pike,Bldg 10,Room 3S239, Bethesda, MD 20892 USA.
OI Ali, Syed/0000-0003-3131-3299
NR 31
TC 28
Z9 29
U1 3
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-878X
J9 NEUROPSY NEUROPSY BE
JI Neuropsychiatr. Neuropsychol. Behav. Neurol.
PD OCT-DEC
PY 2001
VL 14
IS 4
BP 227
EP 232
PG 6
WC Clinical Neurology; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA 491QF
UT WOS:000172119300005
PM 11725216
ER

PT J
AU Seidman, LJ
   Biederman, J
   Monuteaux, MC
   Doyle, AE
   Faraone, SV
AF Seidman, LJ
   Biederman, J
   Monuteaux, MC
   Doyle, AE
   Faraone, SV
TI Learning disabilities and executive dysfunction in boys with
   attention-deficit/hyperactivity disorder
SO NEUROPSYCHOLOGY
LA English
DT Article
ID DEFICIT-HYPERACTIVITY DISORDER; CLINICALLY REFERRED SAMPLE; OSTERRIETH
   COMPLEX FIGURE; READING-DISABILITY; NEUROPSYCHOLOGICAL FUNCTION;
   SUSTAINED ATTENTION; GENETIC ETIOLOGY; CHILDREN; ADHD; COMORBIDITY
AB The effect of comorbid reading or arithmetic learning disabilities (LDs) on neuropsychological function in attention-deficit/hyperactivity disorder (ADHD) was studied. Participants were young males diagnosed with ADHD, with and without LD, and non-ADHD, non-LD male controls of similar age. LD was defined by combined regression-based and low-achievement classifications. Analyses adjusted for the effect of psychiatric comorbidity, age, and socioeconomic status on neuropsychological function. Children who had both ADHD and LD were significantly more impaired on both executive, and nonexecutive functions than ADHD children without LD. Neuropsychological performance was most impaired in ADHD with combined arithmetic and reading disability. These data indicate that comorbid LD, especially arithmetic disability, significantly increases the severity of executive function impairment in ADHD.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit,Dept Psychiat, Boston, MA 02114 USA.
   Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA.
   McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA.
   Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA.
   Massachusetts Gen Hosp, Dept Epidemiol, Boston, MA 02114 USA.
RP Seidman, LJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit,Dept Psychiat, ACC 725,15 Parkman St, Boston, MA 02114 USA.
OI Faraone, Stephen/0000-0002-9217-3982
FU NIMH NIH HHS [R01MH-41314]
NR 72
TC 97
Z9 106
U1 6
U2 15
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD OCT
PY 2001
VL 15
IS 4
BP 544
EP 556
DI 10.1037/0894-4105.15.4.544
PG 13
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA 494KQ
UT WOS:000172281800014
PM 11761044
ER

PT J
AU Kahkonen, S
   Ahveninen, J
   Jaaskelainen, IP
   Kaakkola, S
   Naatanen, R
   Huttunen, J
   Pekkonen, E
AF Kahkonen, S
   Ahveninen, J
   Jaaskelainen, IP
   Kaakkola, S
   Naatanen, R
   Huttunen, J
   Pekkonen, E
TI Effects of haloperidol on selective attention - A combined whole-head
   MEG and high-resolution EEG study
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE auditory; D2 receptors; electroencephalography (EEG); haloperidol;
   magnetoencephalography (MEG); selective attention
ID MISMATCH NEGATIVITY; PROCESSING NEGATIVITY; AUDITORY ATTENTION;
   HUMAN-BRAIN; RECEPTORS; MODULATION; TRANSMISSION; SUPPRESSION;
   VOLUNTEERS; DOPAMINE
AB We used 122-channel magnetoencephalography (MEG) and 64-channel electroencephalogrphy (EEG) simultaneously to study the effects of dopaminergic transmission on human selective attention in a randomized, double-blind placebo-controlled cross-over design. A single dose of dopamine D2 receptor antagonist haloperidol (2 mg) or placebo was given orally to 12 right-handed healthy volunteers 3 hours before measurement. In a dichotic selective attention task, subjects were presented with two trains of standard (700 Hz to the left ear, 1,100 Hz to the right ear) and deviant (770 and 1,210 Hz, respectively) tones. Subjects were instructed to count the tones presented to one ear; whereas, the tones presented to the other ear were to be ignored. Haloperidol significantly attenuated processing negativity (PN), an event-related potential (ERP) component elicited by selectively attended standard tones at 300-500 ins after stimulus presentation. These results, indicating impaired selective attention by a blockade of dopamine D2 receptors, were further accompanied with increased mismatch negativity (MMN), elicited by involuntary detection of task-irrelevant deviants. Taken together, haloperidol seemed to induce functional changes in neural networks accounting for both selective and involuntary attention, suggesting modulation of these functions by dopamine D2 receptors.
C1 Univ Helsinki, Cent Hosp, Med Engn Ctr, BioMag Lab, FIN-00029 HUS, Finland.
   Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, SF-00100 Helsinki, Finland.
   Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland.
   Univ Helsinki, Cent Hosp, Dept Clin Neurophysiol, Helsinki, Finland.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA.
RP Kahkonen, S (reprint author), Univ Helsinki, Cent Hosp, Med Engn Ctr, BioMag Lab, POB 340, FIN-00029 HUS, Finland.
RI Jaaskelainen, Iiro/C-7392-2012
OI Jaaskelainen, Iiro/0000-0001-6001-6950
NR 38
TC 61
Z9 62
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 0893-133X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD OCT
PY 2001
VL 25
IS 4
BP 498
EP 504
DI 10.1016/S0893-133X(01)00255-X
PG 7
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 471YV
UT WOS:000170957000005
PM 11557163
ER

PT J
AU Subramanian, S
   Clark, MA
   Isaacson, K
AF Subramanian, S
   Clark, MA
   Isaacson, K
TI Outcome and resource use associated with myomectomy
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID ABDOMINAL HYSTERECTOMY; ECONOMIC-EVALUATION; MENORRHAGIA; COST;
   RECURRENCE; LEIOMYOMAS; CHARGES
AB OBJECTIVE: To evaluate the outcomes and cost of myomectomy through retrospective claims data analysis.
   METHODS: The study was performed using a retrospective database of private insurance claims from 1995 to 1997. Records were selected for analysis based on the presence of ICD-9-CM procedure and/or CPT-4 codes associated with myomectomy. In addition, diagnosis of uterine leiomyoma and related symptoms for these patients were confirmed through ICD-9-CM diagnosis codes. Inpatient, outpatient, and physician costs were estimated. All cost data were converted into 1997 dollars.
   RESULTS: A total of 4394 women, between the ages of 14 and 70, were available for analysis. Of these, 3305 were classified by type of myomectomy procedure, and complete data were available on 820 at 1 year and 236 at 2 years. Abdominal myomectomies were the most common procedures, followed by hysteroscopic and laparoscopic myomectomies. Conversion to a more invasive procedure occurred in 5.4% of the patients. The rate of additional surgeries was 8.3% in 6 months, 10.6% in 1 year, and 16.5% in 2 years. Overall cost increased from an initial $6,737 per patient to $7,575 in 1 year and to $8,001 in 2 years.
   CONCLUSION: The repeat procedures required after the initial myomectomy add significantly to total cost and highlight the importance of assessing post-procedure health care use. This comprehensive analysis facilitates the systematic evaluation of myomectomy with current and emerging alternative treatments for uterine leiomyomas. (C) 2001 by the American College of Obstetricians and Gynecologists.
C1 Boston Sci Corp, Natick, MA 01760 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Clark, MA (reprint author), Boston Sci Corp, 1 Boston Sci Pl, Natick, MA 01760 USA.
NR 15
TC 34
Z9 36
U1 1
U2 1
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 OCT
PY 2001
VL 98
IS 4
BP 583
EP 587
DI 10.1016/S0029-7844(01)01523-X
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 478XT
UT WOS:000171374400010
PM 11576571
ER

PT J
AU Subak, LL
   Waetjen, LE
   van den Eeden, S
   Thom, DH
   Vittinghoff, E
   Brown, JS
AF Subak, LL
   Waetjen, LE
   van den Eeden, S
   Thom, DH
   Vittinghoff, E
   Brown, JS
TI Cost of pelvic organ prolapse surgery in the United States
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
AB OBJECTIVE: To estimate the annual direct cost to society of pelvic organ prolapse operations in the United States.
   METHODS: We multiplied the number of pelvic organ prolapse operations identified in the 1997 National Hospital Discharge Survey by national average Medicare reimbursement for physician services and hospitalizations. Although this reimbursement does not estimate the actual cost, it is a proxy for cost, which estimates what society pays for the procedures.
   RESULTS: In 1997, direct costs of pelvic organ prolapse surgery were $1012 million (95% confidence interval [CI] $775, 1251 million), including $494 million (49%) for vaginal hysterectomy, $279 million (28%) for cystocele and rectocele repair, and $135 million (13%) for abdominal hysterectomy. Physician services accounted for 29% ($298 million) of total costs, and hospitalization accounted for 71% ($714 million). Twenty-one percent of pelvic organ prolapse operations included urinary incontinence procedures ($218 million). If all operations were reimbursed by non-Medicare sources, the annual estimated cost would increase by 52% to $1543 million.
   CONCLUSION: The annual direct costs of operations for pelvic organ prolapse are substantial. (C) 2001 by the American College of Obstetricians and Gynecologists.)
C1 Univ Calif San Francisco, Mt Zion Womens Hlth, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
   San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA USA.
   Kaiser Permanente Med Ctr, Div Res, Oakland, CA USA.
   San Francisco Vet Affairs med Ctr, Gen Internal Med Sect, Oakland, CA USA.
   Stanford Univ, Div Family & Community Med, Palo Alto, CA 94304 USA.
RP Subak, LL (reprint author), Univ Calif San Francisco, Mt Zion Womens Hlth, Dept Obstet Gynecol & Reprod Sci, 2330 Post St,Suite 200, San Francisco, CA 94143 USA.
FU NIA NIH HHS [1K08AG00710-01A1]; NICHD NIH HHS [K12 HD01262-02]
NR 15
TC 249
Z9 269
U1 0
U2 6
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 OCT
PY 2001
VL 98
IS 4
BP 646
EP 651
DI 10.1016/S0029-7844(01)01472-7
PG 6
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 478XT
UT WOS:000171374400021
PM 11576582
ER

PT J
AU Li, W
   Fan, JH
   Woodley, DT
AF Li, W
   Fan, JH
   Woodley, DT
TI Nck/Dock: an adapter between cell surface receptors and the actin
   cytoskeleton
SO ONCOGENE
LA English
DT Review
DE Src-homology domains; adapters; tyrosine kinases; signal transduction;
   cytoskeleton
ID GROWTH-FACTOR RECEPTOR; PROTEIN-TYROSINE-PHOSPHATASE; GUANINE-NUCLEOTIDE
   EXCHANGE; INTRACELLULAR SIGNAL-TRANSDUCTION; PHOTORECEPTOR AXON
   GUIDANCE; SMOOTH-MUSCLE CELLS; SH2 DOMAIN PROTEINS; P21-ACTIVATED
   KINASE; EPH RECEPTORS; PHOSPHATIDYLINOSITOL 3-KINASE
AB In response to extracellular signals, cell surface receptors engage in connections with multiple intracellular signaling pathways, leading to the cellular responses such as survival, migration, proliferation and differentiation. The 'pY --> SH2/SH3 --> effector' connection is a frequently used scheme by many cell surface receptors, in which SH2/SH3-containing adapters connect protein tyrosine phosphorylation to a variety of downstream effector pathways. Following the initial landmark finding that Grb2 adapter links the receptors to the Ras pathway leading to DNA synthesis, recent studies have revealed that the biological function of the SH2/SH3 adapter Nck/Dock is to link cell surface receptors to the actin cytoskeleton. For example, in the evolutionarily-conserved signaling network, GEF-Rae-Nck-Pak, Nck 'fixes up' the interaction of Pak with its upstream activator, Rac. The activated Pak then regulates the cytoskeletal dynamics. The fact that the majority of the more than 20 Nck-SH3-associated effectors are regulators of the actin cytoskeleton suggests that Nck/Dock regulates, via binding to distinct effectors, various cell type-specific motogenic responses. This review focuses on our current understanding of Nck/Dock function. Due to the number and complexity of the terminologies used in this review, a 'Glossary of Terms' is provided to help reduce confusions.
C1 Univ So Calif, Sch Med, Dept Med, Div Dermatol, Los Angeles, CA 90033 USA.
   Univ So Calif, Sch Med, Norris Cotton Canc Ctr, Los Angeles, CA 90033 USA.
   Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA.
RP Li, W (reprint author), Univ So Calif, Sch Med, Dept Med, Div Dermatol, Los Angeles, CA 90033 USA.
FU NCI NIH HHS [CA65567]; NIAMS NIH HHS [AR46538]
NR 124
TC 108
Z9 109
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD OCT 1
PY 2001
VL 20
IS 44
BP 6403
EP 6417
DI 10.1038/sj.onc.1204782
PG 15
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 483NF
UT WOS:000171640600014
PM 11607841
ER

PT J
AU Jafarnia, K
   Gabel, GT
   Morrey, BF
AF Jafarnia, K
   Gabel, GT
   Morrey, BF
TI Triceps tendinitis
SO OPERATIVE TECHNIQUES IN SPORTS MEDICINE
LA English
DT Article
DE triceps tendinitis; olecranon spur
ID ELBOW
AB Elbow extension is very critical for the throwing athlete. The extensor mechanism of the elbow is a relatively uncommon source of clinical dysfunction. However, two primary processes may affect the triceps tendon, triceps tendonitis, and triceps avulsion injuries. Triceps tendonitis, the more common of the two, is manifested by chronic posterior elbow pain with extension activities. It occurs almost exclusively in males, usually in the fourth decade of life, and especially in individuals who perform forceful repetitive extension activities, eg, throwing athletes. Two distinct subsets of patients exist: those with and those without an olecranon traction spur. Conservative management involves avoidance of repetitive forceful elbow extension, nonsteroidal anti-inflammatories, and time. Splinting in 45 degrees of elbow flexion may be useful if tolerated. Counterforce bracing is typically unsuccessful because the cross-section of the arm changes with biceps contraction. Corticosteroid injection is contraindicated. Although conservative management is limited in scope, it is usually successful in triceps tendonitis in the absence of an olecranon traction spur. The presence of an olecranon traction spur is associated with a higher failure rate of conservative treatment necessitating surgical intervention. Surgical management, when required, involves subperiosteal exposure and excision of the spur and the olecranon tip and formal repair of the triceps tendon.
C1 Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA.
   Baylor Coll Med, Dept Orthoped Surg, Houston, TX 77030 USA.
   Mayo Clin, Dept Orthoped Surg, Rochester, MN USA.
RP Jafarnia, K (reprint author), Harvard Univ, Sch Med, Dept Orthoped Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA.
OI jafarnia, kourosh/0000-0002-8106-4705
NR 5
TC 5
Z9 5
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 1060-1872
J9 OPER TECHN SPORT MED
JI Oper. Tech. Sports Med.
PD OCT
PY 2001
VL 9
IS 4
BP 217
EP 221
DI 10.1053/otsm.2001.26782
PG 5
WC Sport Sciences; Surgery
SC Sport Sciences; Surgery
GA 490AA
UT WOS:000172024500005
ER

PT J
AU Lin, AL
   Johnson, DA
   Patterson, TF
   Wu, Y
   Lu, DL
   Shi, Q
   Yeh, CK
AF Lin, AL
   Johnson, DA
   Patterson, TF
   Wu, Y
   Lu, DL
   Shi, Q
   Yeh, CK
TI Salivary anticandidal activity and saliva composition in an HIV-infected
   cohort
SO ORAL MICROBIOLOGY AND IMMUNOLOGY
LA English
DT Article
DE saliva composition; HIV/AIDS; anticandidal activity
ID HISTIDINE-RICH POLYPEPTIDES; HUMAN PAROTID-SALIVA; CANDIDA-ALBICANS;
   DEFENSE-MECHANISMS; ORAL CANDIDIASIS; HEALTHY-ADULTS; AIDS PATIENTS;
   HISTATINS; PROTEINS; ANTIBODIES
AB This study investigated salivary anticandidal activity and salivary composition in stimulated whole saliva of 18 advanced HIV-infected patients and compared these values to healthy controls. Stimulated whole saliva from HIV-infected patients showed decreased anticandidal activity. The flow rate was reduced by 40% as compared with controls. The saliva flow rate for HIV-infected patients who had recoverable yeast in their saliva was reduced as compared to HIV-infected patients without recoverable yeast. For HIV-infected patients, the saliva concentrations of lactoferrin, secretory IgA and Cl- were increased while the secretion rate of lysozyme, total protein and K+ were reduced. There was no difference in any parameter as a function of taking the antifungal drug fluconazole. There was no association between salivary anticandidal activity and any salivary component. This study shows reduced anticandidal activity and salivary flow rate in HIV-infected patients. These alterations may contribute to their increased incidence of oral candidal infections.
C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78284 USA.
   Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX USA.
   Univ Texas, Hlth Sci Ctr, Dept Community Dent, San Antonio, TX USA.
   Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX USA.
RP Yeh, CK (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78284 USA.
FU NIDCR NIH HHS [DE-11381, DE-12188]
NR 42
TC 31
Z9 31
U1 2
U2 6
PU MUNKSGAARD INT PUBL LTD
PI COPENHAGEN
PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK
SN 0902-0055
J9 ORAL MICROBIOL IMMUN
JI Oral Microbiol. Immunol.
PD OCT
PY 2001
VL 16
IS 5
BP 270
EP 278
DI 10.1034/j.1399-302x.2001.016005270.x
PG 9
WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology
SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology
GA 470CZ
UT WOS:000170854000003
PM 11555303
ER

PT J
AU Duncan, CP
   Rubash, HE
AF Duncan, CP
   Rubash, HE
TI Instability after major joint replacement - Preface
SO ORTHOPEDIC CLINICS OF NORTH AMERICA
LA English
DT Editorial Material
C1 Univ British Columbia, Dept Orthopaed, Vancouver, BC V5Z 4R3, Canada.
   Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA.
RP Duncan, CP (reprint author), Univ British Columbia, Dept Orthopaed, 3rd Floor,910 W 10th Ave, Vancouver, BC V5Z 4R3, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 0030-5898
J9 ORTHOP CLIN N AM
JI Orthop. Clin. North Am.
PD OCT
PY 2001
VL 32
IS 4
BP XIII
EP XIII
PG 1
WC Orthopedics
SC Orthopedics
GA 501KZ
UT WOS:000172685000001
ER

PT J
AU Gerber, A
   Ghalambor, N
   Warner, JJP
AF Gerber, A
   Ghalambor, N
   Warner, JJP
TI Instability of shoulder arthroplasty - Balancing mobility and stability
SO ORTHOPEDIC CLINICS OF NORTH AMERICA
LA English
DT Article
ID HUMERAL HEAD
AB Avoidance of instability after shoulder arthroplasty is based on an appreciation of normal articular anatomy and its restoration, as well as adequate soft tissue release and secure repair of subscapularis. Errors in restoration of articular anatomy, or disruption of soft tissues about the joint, are the principal reasons for instability. Revision in such cases can be challenging because of difficulties in restoring normal articular position and orientation, as well as reconstruction of deficient soft tissues.
C1 Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, Boston, MA 02114 USA.
RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Shoulder Serv, 275 Cambridge St, Boston, MA 02114 USA.
RI Gerber Popp, Ariane/O-2781-2014
OI Gerber Popp, Ariane/0000-0002-6798-3676
NR 44
TC 9
Z9 9
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 0030-5898
J9 ORTHOP CLIN N AM
JI Orthop. Clin. North Am.
PD OCT
PY 2001
VL 32
IS 4
BP 661
EP +
DI 10.1016/S0030-5898(05)70235-2
PG 11
WC Orthopedics
SC Orthopedics
GA 501KZ
UT WOS:000172685000012
PM 11689378
ER

PT J
AU Ring, D
   Koris, M
   Jupiter, JB
AF Ring, D
   Koris, M
   Jupiter, JB
TI Instability after total elbow arthroplasty
SO ORTHOPEDIC CLINICS OF NORTH AMERICA
LA English
DT Article
ID RHEUMATOID-ARTHRITIS; TOTAL REPLACEMENT; JOINT; DISLOCATION; PROSTHESIS;
   STABILITY
AB Resurfacing total elbow arthroplasty is occasionally unstable. Instability may be related to insufficiency of the ligaments or improper tensioning and implant positioning at the time of surgery. Ligament reconstruction has produced mixed results; however, attempts to reconstruct the ligaments are probably worthwhile because conversion of a freshly cemented resurfacing implant to a semiconstrained hinge is very challenging.
C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand Surg Serv, Boston, MA 02114 USA.
   Brigham & Womens Hosp, Dept Orthopaed Surg, Upper Extrem Serv, Boston, MA 02115 USA.
RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand Surg Serv, ACC 525,15 Parkman St, Boston, MA 02114 USA.
NR 46
TC 9
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 0030-5898
J9 ORTHOP CLIN N AM
JI Orthop. Clin. North Am.
PD OCT
PY 2001
VL 32
IS 4
BP 671
EP +
DI 10.1016/S0030-5898(05)70236-4
PG 8
WC Orthopedics
SC Orthopedics
GA 501KZ
UT WOS:000172685000013
PM 11689379
ER

PT J
AU Santosham, M
   Englund, JA
   McInnes, P
   Croll, J
   Thompson, CM
   Croll, L
   Glezen, WP
   Siber, GR
AF Santosham, M
   Englund, JA
   McInnes, P
   Croll, J
   Thompson, CM
   Croll, L
   Glezen, WP
   Siber, GR
TI Safety and antibody persistence following Haemophilus influenzae type b
   conjugate or pneumococcal polysaccharide vaccines given before pregnancy
   in women of childbearing age and their infants
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE antibody; Haemophilus influenzae type b conjugate; vaccine; pneumococcal
   polysaccharide vaccine; prepregnancy vaccination
ID HIGH-RISK INFANTS; CAPSULAR POLYSACCHARIDE; MATERNAL IMMUNIZATION; SERUM
   ANTIBODIES; TOXOID CONJUGATE; IMMUNE GLOBULIN; CHILDREN
AB Background. Immunization of healthy women before pregnancy is a potential approach to providing increased levels of maternal antibody to newborns to protect them from infections occurring during the perinatal period and first months of life.
   Methods. Healthy nonpregnant Pima Indian women of childbearing age were randomized to receive one of two Haemophilus influenzae type b (Hib) conjugate vaccines [HbOC or Hib-meningococcal outer membrane protein complex (OMP)] or a 23-valent pneumococcal polysaccharide vaccine (PnPs). Infants received Hib-OMP vaccine at 2, 4 and 12 months of age. Vaccine safety and immunogenicity was evaluated in the women and their infants.
   Results. Anti-polyribose ribitol phosphate antibody titers were significantly higher in women in both Hib conjugate vaccine groups than in the pneumococcal vaccine group throughout the 37-month observation period. Antibody responses to HbOC vaccine were significantly higher than those to Hib-OMP. A subsequent booster dose of each Hib conjugate vaccine induced reactions and antibody responses similar to those of the first dose. Infants born to mothers immunized with Hib vaccines compared with PnPs had significantly higher polyribose ribitol phosphate-specific IgG antibody titers at birth and 2 months of age but lower antibody responses to Hib-OMP at 6 months and similar titers before and after boosting with Hib-OMP at 1 year of age. By contrast women immunized with PnPs did not have significantly elevated concentrations of pneumococcal-specific antibody at delivery, and their infants had pneumococcal antibody titers similar to those of infants born to mothers who did not receive pneumococcal vaccine before pregnancy.
   Conclusion. Hib conjugate vaccine given to women before pregnancy significantly increased the proportion of infants who had protective Hib antibody levels at birth and 2 months of age.
C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Ctr Amer Indian & Alaskan Nat Hlth, Baltimore, MD 21205 USA.
   Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
   NIAID, NIH, Bethesda, MD 20892 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA.
   Wyeth Lederle Vaccines & Pediat, Pearl River, NY USA.
RP Santosham, M (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth, Ctr Amer Indian & Alaskan Nat Hlth, 615 N Wolfe St,B Suite E8132, Baltimore, MD 21205 USA.
RI Sandall, Jane/D-4146-2009
OI Sandall, Jane/0000-0003-2000-743X
NR 25
TC 23
Z9 24
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0891-3668
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD OCT
PY 2001
VL 20
IS 10
BP 931
EP 940
DI 10.1097/00006454-200110000-00005
PG 10
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA 481PX
UT WOS:000171529500003
PM 11642626
ER

PT J
AU Wolraich, ML
   Greenhill, LL
   Pelham, W
   Swanson, J
   Wilens, T
   Palumbo, D
   Atkins, M
   McBurnett, K
   Bukstein, O
   August, G
AF Wolraich, ML
   Greenhill, LL
   Pelham, W
   Swanson, J
   Wilens, T
   Palumbo, D
   Atkins, M
   McBurnett, K
   Bukstein, O
   August, G
CA Concerta Study Grp
TI Randomized, controlled trial of OROS methylphenidate once a day in
   children with attention-deficit/hyperactivity disorder
SO PEDIATRICS
LA English
DT Article
DE attention-deficit/hyperactivity disorder; methylphenidate; OROS;
   Concerta
ID PLACEBO-CONTROLLED EVALUATION
AB Objective. A new once-a-day methylphenidate (MPH) formulation, Concerta (methylphenidate HCl) extended-release tablets (OROS MPH), has been developed. This study was conducted to determine the safety and efficacy of OROS MPH in a multicenter, randomized, clinical trial.
   Methods. Children with attention-deficit/hyperactivity disorder (ADHD; n = 282), all subtypes, ages 6 to 12 years, were randomized to placebo (n = 90), immediate-release methylphenidate (IR MPH) 3 times a day (tid; dosed every 4 hours; n = 97), or OROS MPH once a day (qd; n = 95) in a double-blind, 28-day trial. Outcomes in multiple domains were assessed, and data were analyzed using analysis of variance and Kaplan Meier product limit estimates for time to study cessation. The primary time point for analysis was the last available patient visit using last observation carried forward.
   Results. Children in the OROS and IR MPH groups showed significantly greater reductions in core ADHD symptoms than did children on placebo. This was true both at the end of week 1 and at the end of treatment on the basis of mean teacher and parent IOWA Conners ratings. IR MPH tid and OROS MPH qd did not differ significantly on any direct comparisons. Forty-eight percent of the placebo group discontinued early compared with 14% and 16% in the IR MPH and OROS MPH groups, respectively.
   Conclusions. For the treatment of core ADHD symptoms, OROS MPH dosed qd and IR MPH dosed tid were superior to placebo and were not significantly different from each other.
C1 Vanderbilt Univ, Nashville, TN USA.
   New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
   SUNY Buffalo, Buffalo, NY 14260 USA.
   Univ Calif Irvine, Irvine, CA USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Univ Rochester, Rochester, MN USA.
   Univ Illinois, Chicago, IL USA.
   Univ Chicago, Chicago, IL 60637 USA.
   Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA.
   Univ Minnesota, Rochester, MN USA.
RP Wolraich, ML (reprint author), Ctr Child Study, 1100 NE 13th St, Oklahoma City, OK 73117 USA.
NR 21
TC 217
Z9 224
U1 1
U2 20
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 OCT
PY 2001
VL 108
IS 4
BP 883
EP 892
DI 10.1542/peds.108.4.883
PG 10
WC Pediatrics
SC Pediatrics
GA 478AC
UT WOS:000171319600029
PM 11581440
ER

PT J
AU Kuhlthau, K
   Ferris, TGG
   Beal, AC
   Gortmaker, SL
   Perrin, JM
AF Kuhlthau, K
   Ferris, TGG
   Beal, AC
   Gortmaker, SL
   Perrin, JM
TI Who cares for Medicaid-enrolled children with chronic conditions?
SO PEDIATRICS
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Pediatric-Academic-Societies
CY MAY 01-04, 1999
CL SAN FRANCISCO, CALIFORNIA
SP Pediat Acad Soc
DE children; chronic conditions; Medicaid; subspecialist; generalist;
   primary care; referral; Supplemental Security Income
ID HOSPITALIZATION; PEDIATRICIANS; ADOLESCENTS; GENERALIST; PHYSICIANS;
   PREVALENCE; CHILDHOOD; DISEASE; IMPACT; VOLUME
AB Objective. To estimate generalist, pediatric subspecialist, and any subspecialist use by Medicaid-enrolled children with chronic conditions and to determine the correlates of use.
   Methods. We analyzed Medicaid claims data collected from 1989 to 1992 from 4 states for 57 328 children and adolescents with 11 chronic conditions. We calculated annual rates of generalist, subspecialist, and pediatric subspecialist use. We used logistic regression to determine the association of demographics, urban residence, and case-mix (Adjusted Clinical Groups) with the use of relevant pediatric and any subspecialist care.
   Results. Most children with chronic conditions had visits to generalists (range per condition: 78%-90% for children with Supplemental Security Income [SSI] and 85%-94% for children without SSI) during the year studied. Fewer children visited any relevant subspecialists (24%-59% for children with SSI and 13%-56% for children without SSI) or relevant pediatric subspecialists (10%-53% for children with SSI and 3%-37% for children without SSI). In general, children who were more likely to use pediatric subspecialists were younger, lived in urban areas, were white (only significant for non-SSI children), and had higher Adjusted Clinical Groups scores. Use of any subspecialists followed a similar pattern except that urban residence is statistically significant only for children with SSI and the youngest age group does not differ from the oldest age group for children without SSI.
   Conclusions. Children who had chronic conditions and were enrolled in Medicaid received a majority of their care from generalist physicians. For most conditions, a majority of children did not receive any relevant subspecialty care during the year and many of these children did not receive care form providers with pediatric-specific training.
C1 MassGen Hosp Children, Ctr Child & Adolescent Hlth, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Massachusetts Gen Hosp, Inst Hlth Policy, Div Gen Med, Boston, MA 02114 USA.
   Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA.
RP Kuhlthau, K (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth, 50 Staniford St,Suite 901, Boston, MA 02114 USA.
FU NICHD NIH HHS [HD00850]
NR 21
TC 71
Z9 71
U1 1
U2 3
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 OCT
PY 2001
VL 108
IS 4
BP 906
EP 912
DI 10.1542/peds.108.4.906
PG 7
WC Pediatrics
SC Pediatrics
GA 478AC
UT WOS:000171319600032
PM 11581443
ER

PT J
AU McGuirk, CK
   Westgate, MN
   Holmes, LB
AF McGuirk, CK
   Westgate, MN
   Holmes, LB
TI Limb deficiencies in newborn infants
SO PEDIATRICS
LA English
DT Article
DE limb deficiency; vascular disruption
ID FIRST-TRIMESTER; REDUCTION DEFECTS; PREGNANCY; ABNORMALITIES;
   MALFORMATIONS; DISRUPTION; MUTATIONS; ANOMALIES; TRAUMA
AB Objective. The prevalence rate of all types of limb reduction defects in general and those that potentially are caused by vascular disruption in particular is needed to provide a baseline for the evaluation of infants who are exposed in utero to teratogens that cause vascular disruption. The objective of this study was to determine this prevalence rate.
   Methods. All infants with any limb deficiency among 161252 liveborn and stillborn infants and elective terminations were identified in a hospital-based Active Malformations Surveillance Program in Boston in the years 1972 to 1974 and 1979 to 1994. An extensive search was made to identify infants who were missed by the Surveillance Program; an additional 8 infants (7.3% of total) were identified. The limb reduction defects were classified in 3 ways: 1) by the anatomic location of the defect, that is longitudinal, terminal, intercalary, etc; 2) for infants with absence/hypoplasia of fingers or toes, a tabulation of which digit or digits were affected; and 3) by apparent cause.
   Results. The prevalence rate for all types of limb deficiency was 0.69/1000. The apparent causes included single mutant genes, familial occurrence, and known syndromes (24%); chromosome abnormalities (6%); teratogens (4%); vascular disruption (35%); and unknown cause (32%).
   Conclusions. A hospital-based surveillance program can be used to establish the prevalence of limb reduction defects, if ascertainment is extended to include elective terminations for fetal abnormalities. An apparent cause can be established for most limb defects when the clinical findings are used rather than reliance only on the International Classification of Diseases, Ninth Revision, codes of the discharge diagnoses. The prevalence rate of limb reduction defects as a result of presumed vascular disruption was 0.22/1000.
C1 Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA.
   Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP McGuirk, CK (reprint author), Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Warren 801,55 Fruit St, Boston, MA 02114 USA.
FU NICHD NIH HHS [HD 33222]
NR 26
TC 55
Z9 57
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 OCT
PY 2001
VL 108
IS 4
BP art. no.
EP e64
DI 10.1542/peds.108.4.e64
PG 7
WC Pediatrics
SC Pediatrics
GA 478AC
UT WOS:000171319600007
PM 11581472
ER

PT J
AU Pestonjamasp, VK
   Huttner, KH
   Gallo, RL
AF Pestonjamasp, VK
   Huttner, KH
   Gallo, RL
TI Processing site and gene structure for the murine antimicrobial peptide
   CRAMP
SO PEPTIDES
LA English
DT Article
DE innate immunity; neutrophils; antibiotic; mouse
ID TRACHEAL EPITHELIAL-CELLS; ANTIBACTERIAL PEPTIDE; BONE-MARROW; BOVINE
   NEUTROPHILS; BINDING PROTEIN; HOST-DEFENSE; HUMAN CAP18; EXPRESSION;
   PR-39; LL-37
AB Cathelicidins are a mammalian gene family notable for the presence of an antibiotic peptide encoded at the carboxy-terminal domain of the nascent pre-pro-protein. Following proteolytic release, this peptide has direct antimicrobial activity. To understand the function and regulation of cathelicidin we investigated the peptide processing site and gene structure of the mouse cathelicidin CRAMP. Amino acid sequencing of the purified native 5 kDa peptide identified the functionally critical amino terminal sequence of mature CRAMP. Characterization of the CRAMP gene (Cnlp) showed homology in structure and sequence identity in several potential transcription factors binding sites found in the human cathelicidin LL-37. Overall, CRAMP shows striking similarities with LL-37, making it a useful model for study of human cathelicidin function and regulation. (C) 2001 Elsevier Science Inc. All rights reserved.
C1 Univ Calif San Diego, Div Dermatol, San Diego, CA 92103 USA.
   VA San Diego, Healthcare Syst, San Diego, CA USA.
   Massachusetts Gen Hosp, Div Newborn Med, Boston, MA 02114 USA.
RP Gallo, RL (reprint author), Univ Calif San Diego, Div Dermatol, San Diego, CA 92103 USA.
RI Gallo, Richard/A-8931-2009
FU NIAID NIH HHS [AI-48176]; NIAMS NIH HHS [AR-44379]
NR 50
TC 42
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 0196-9781
J9 PEPTIDES
JI Peptides
PD OCT
PY 2001
VL 22
IS 10
BP 1643
EP 1650
DI 10.1016/S0196-9781(01)00499-5
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
   Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
   Pharmacology & Pharmacy
GA 480ZE
UT WOS:000171492600013
PM 11587792
ER

PT J
AU Good, CB
AF Good, CB
TI Topical beta-blockers in patients with co-existing conditions: is this a
   cause for concern?
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Editorial Material
ID DEPRESSION; HYPERTENSION; ASSOCIATION; TIMOLOL
C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA.
RP Good, CB (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr C, Pittsburgh, PA 15240 USA.
NR 14
TC 3
Z9 3
U1 0
U2 0
PU JOHN WILEY & SONS LTD
PI W SUSSEX
PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND
SN 1053-8569
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD OCT-NOV
PY 2001
VL 10
IS 6
BP 509
EP 510
DI 10.1002/pds.633
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 514EX
UT WOS:000173426600005
PM 11828832
ER

PT J
AU Runnebaum, IB
   Wang-Gohrke, S
   Vesprini, D
   Kreienberg, R
   Lynch, H
   Moslehi, R
   Ghadirian, P
   Weber, B
   Godwin, AK
   Risch, H
   Garber, J
   Lerman, C
   Olopade, OI
   Foulkes, WD
   Karlan, B
   Warner, E
   Rosen, B
   Rebbeck, T
   Tonin, P
   Dube, MP
   Kieback, DG
   Narod, SA
AF Runnebaum, IB
   Wang-Gohrke, S
   Vesprini, D
   Kreienberg, R
   Lynch, H
   Moslehi, R
   Ghadirian, P
   Weber, B
   Godwin, AK
   Risch, H
   Garber, J
   Lerman, C
   Olopade, OI
   Foulkes, WD
   Karlan, B
   Warner, E
   Rosen, B
   Rebbeck, T
   Tonin, P
   Dube, MP
   Kieback, DG
   Narod, SA
TI Progesterone receptor variant increases ovarian cancer risk in BRCA1 and
   BRCA2 mutation carriers who were never exposed to oral contraceptives
SO PHARMACOGENETICS
LA English
DT Article
DE progesterone receptor; oral contraception; hereditary ovarian cancer;
   hereditary breast cancer
ID BREAST-CANCER; POLYMORPHISM; REPEAT; GENE
AB Oral contraceptives have been shown to be protective against hereditary ovarian cancer. The variant progesterone receptor allele named PROGINS is characterized by an Alu insertion into intron G and two additional mutations in exons 4 and 5. The PROGINS allele codes for a progesterone receptor with increased stability and increased hormone-induced transcriptional activity. We studied the role of the PROGINS allele as a modifying gene in hereditary breast and ovarian cancer. The study included 195 BRCA1 and BRCA2 carriers with a prior diagnosis of ovarian cancer, 392 carriers with a diagnosis of breast cancer and 249 carriers with neither cancer. Fifty-eight women had both forms of cancer. Five hundred and ninety-five women had a BRCA1 mutation and 183 women had a BRCA2 mutation. Overall, there was no association between disease status and the presence of the PROGINS allele. Information on oral contraception use was available for 663 of the 778 carriers of BRCA1 or BRCA2 mutations. Among the 449 subjects with a history of oral contraceptive use (74 cases and 365 controls), no modifying effect of PROGINS was observed [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.5-1.3]. Among the 214 carriers with no past exposure to oral contraceptives, the presence of one or more PROGINS alleles was associated with an OR of 2.4 for ovarian cancer, compared to women without ovarian cancer and with no PROGINS allele (P = 0.004; 95% Cl 1.4-4.3). The association was present after adjustment for ethnic group and for year of birth. Pharmacogenetics 11:635-638 (C) 2001 Lippincott Williams & Wilkins.
C1 Univ Toronto, Ctr Res Womens Hlth, Toronto, ON M5G 1N8, Canada.
   Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
   Univ Freiburg, Dept Obstet & Gynecol, Freiburg, Germany.
   Creighton Univ, Omaha, NE 68178 USA.
   Ctr Hosp Univ Montreal, Montreal, PQ H3C 3J7, Canada.
   Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA.
   Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
   Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
   Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA.
   Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA.
   Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Div Med Sci, New Haven, CT 06510 USA.
   Dana Farber Canc Inst, Div Med Sci, Boston, MA 02115 USA.
   Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Div Med Sci, Washington, DC 20007 USA.
   Univ Chicago, Dept Med, Hematol Oncol Sect, Div Med Sci, Chicago, IL 60637 USA.
   McGill Univ, Dept Med, Div Med Sci, Montreal, PQ, Canada.
   McGill Univ, Dept Human Genet & Oncol, Div Med Sci, Montreal, PQ, Canada.
   Cedars Sinai Med Ctr, Div Med Sci, Los Angeles, CA USA.
   Toronto Sunnybrook Reg Canc Ctr, Div Med Sci, Toronto, ON, Canada.
   Toronto Hosp, Dept Obstet & Gynecol, Div Med Sci, Toronto, ON M5T 2S8, Canada.
RP Narod, SA (reprint author), Univ Toronto, Ctr Res Womens Hlth, 790 Bay St, Toronto, ON M5G 1N8, Canada.
RI Dube, Marie-Pierre/B-9364-2008
OI Dube, Marie-Pierre/0000-0001-8442-4393
NR 8
TC 32
Z9 32
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0960-314X
J9 PHARMACOGENETICS
JI Pharmacogenetics
PD OCT
PY 2001
VL 11
IS 7
BP 635
EP 638
DI 10.1097/00008571-200110000-00010
PG 4
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
   & Pharmacy
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology
   & Pharmacy
GA 483LF
UT WOS:000171636300010
PM 11668223
ER

PT J
AU Hsu, SIH
AF Hsu, SIH
TI Biopsy-proved acute tubulointerstitial nephritis and toxic epidermal
   necrolysis associated with vancomycin
SO PHARMACOTHERAPY
LA English
DT Article
ID ACUTE INTERSTITIAL NEPHRITIS; PHARMACOKINETICS; HEMODIALYSIS;
   METHICILLIN; THERAPY
AB A 70-year-old man receiving vancomycin for a methicillin-resistant Staphylococcus aureus (MRSA) abscess developed a drug-induced hypersensitivity reaction with rash, eosinophilia, and acute renal failure requiring dialysis. Renal biopsy revealed diffuse and marked interstitial and tubular infiltration by mononuclear cells and eosinophils; acute tubulointerstitial nephritis (TIN) was diagnosed. The rash progressed to erythema multiforme major after rechallenge with vancomycin in the setting of MRSA peritoneal catheter-related peritonitis and then to fatal toxic epidermal necrolysis in the setting of steroid taper and persistent serum vancomycin levels. This case further implicates vancomycin as a drug that infrequently can cause severe acute TIN and exfoliative dermatitis. When a renally excreted drug such as vancomycin is administered, serum drug levels should be serially monitored and high-dosage steroids be maintained or tapered slowly until serum drug levels become undetectable.
C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Hsu, SIH (reprint author), Natl Univ Singapore Hosp, Dept Med, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore.
FU NIDDK NIH HHS [T32 DK07540]
NR 35
TC 25
Z9 26
U1 0
U2 0
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 OCT
PY 2001
VL 21
IS 10
BP 1233
EP 1239
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 478QN
UT WOS:000171357000012
PM 11601669
ER

PT J
AU Shen, QX
   Gomez-Cadenas, A
   Zhang, PG
   Walker-Simmons, MK
   Sheen, J
   Ho, THD
AF Shen, QX
   Gomez-Cadenas, A
   Zhang, PG
   Walker-Simmons, MK
   Sheen, J
   Ho, THD
TI Dissection of abscisic acid signal transduction pathways in barley
   aleurone layers
SO PLANT MOLECULAR BIOLOGY
LA English
DT Article
DE ABA signal transduction; ABI1; alpha-amylase; barley aleurone layer;
   PKABA1; VP1
ID PROTEIN PHOSPHATASE 2C; ALPHA-AMYLASE GENE; RESPONSE COMPLEX; NEGATIVE
   REGULATOR; SEED MATURATION; HIGHER-PLANTS; EXPRESSION; GIBBERELLIN;
   PROMOTER; MAIZE
AB Abscisic acid (ABA) induces genes that are highly expressed during late embryogenesis, but suppresses gibberellin (GA)-responsive genes essential for seed germination and seedling growth. Promoter elements necessary and sufficient for ABA up- and down-regulation of gene expression have been previously defined in barley aleurone layers. We have studied the effect of a protein phosphatase 2C, ABI1, an ABA-inducible protein kinase, PKABA1, and a transcription factor, VP1, on ABA action in a barley aleurone transient expression system. The observations have allowed us to dissect ABA signal transduction pathways leading to either induction or suppression of gene expression. The ABA induction of embryogenesis genes is highly inhibited in the presence of a mutated protein phosphatase 2C, encoded by the abi1-1 dominant mutant gene that is known to block ABA responses in Arabidopsis. However, the abi1-1 gene product has no effect on the ABA suppression of a GA-responsive alpha -amylase gene. On the other hand, PKABA1 suppresses the expression of alpha -amylase genes, but has little effect on ABA up-regulated genes. Therefore, it appears that ABA induction and suppression follow two separate signal transduction pathways with the former inhibited by ABI1 and the latter modulated by PKABA1. The presence of VP1 enhances the ABA induction of late embryogenesis genes, but also suppresses germination specific genes. A schematic model based on these observations is presented to explain the effect of these regulatory proteins on ABA-mediated gene expression.
C1 Washington Univ, Dept Biol, Div Biol & Biomed Sci, Plant Biol Program, St Louis, MO 63130 USA.
   Washington State Univ, USDA ARS, Pullman, WA 99164 USA.
   Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Ho, THD (reprint author), Washington Univ, Dept Biol, Div Biol & Biomed Sci, Plant Biol Program, Campus Box 1137, St Louis, MO 63130 USA.
RI Gomez-Cadenas, Aurelio/K-6084-2012
OI Gomez-Cadenas, Aurelio/0000-0002-4598-2664
NR 51
TC 28
Z9 40
U1 0
U2 4
PU KLUWER ACADEMIC PUBL
PI DORDRECHT
PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
SN 0167-4412
J9 PLANT MOL BIOL
JI Plant Mol.Biol.
PD OCT
PY 2001
VL 47
IS 3
BP 437
EP 448
DI 10.1023/A:1011667312754
PG 12
WC Biochemistry & Molecular Biology; Plant Sciences
SC Biochemistry & Molecular Biology; Plant Sciences
GA 468ZE
UT WOS:000170787400009
PM 11587514
ER

PT J
AU Lee, WPA
   Butler, PEM
   Randolph, MA
   Yaremchuk, MJ
AF Lee, WPA
   Butler, PEM
   Randolph, MA
   Yaremchuk, MJ
TI Donor modification leads to prolonged survival of limb allografts
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID VASCULARIZED BONE ALLOGRAFTS; EXPERIMENTAL SKIN ALLOGRAFTS; EPIDERMAL
   LANGERHANS CELLS; SKELETAL TISSUE ALLOGRAFTS; LONG-TERM SURVIVAL;
   CYCLOSPORIN-A; IMMUNOLOGICAL-UNRESPONSIVENESS; INDEFINITE SURVIVAL;
   NERVE ALLOGRAFTS; TRANSPLANTATION
AB Chronic immunosuppression is essential for maintaining human hand transplant survival because composite tissue allografts are as susceptible to rejection as visceral organ allografts. Limb allografts comprise different types of tissues with varying antigenicities, and the immunosuppressive doses required for these allografts are as high or higher than those required for solid organ allotransplantation. In particular, bone marrow is all early target of the host immune response. This study reports on donor limb modification of the marrow compartment leading to prolonged survival of limb allografts.
   Chimeric limb allografts comprising a Lewis rat vascularized allograft and Brown Norway rat bone marrow were created. These chimeric limbs were transplanted into three recipients: (1) Buffalo rats (n = 12), where the chimeric limb was allogeneic for both vascular graft and bone marrow; (2) Lewis rats (n = 12), where the limb was allogeneic for marrow alone; and (3) Brown Norway rats (n = 12), where the limb was allogeneic for graft alone.
   This study found that Brown Norway recipients elicited significantly reduced cell-mediated and humoral immune responses in comparison with the Buffalo and Lewis recipients (p < 0.001 and p < 0.01, respectively). The Buffalo and Lewis recipients both elicited high cell-mediated and humoral responses. The Brown Norway recipients also had prolonged survival of limb tissue allograft ill comparison with the other experimental groups.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA.
RP Lee, WPA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WAC 453,15 Parkman St, Boston, MA 02114 USA.
NR 44
TC 19
Z9 21
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD OCT
PY 2001
VL 108
IS 5
BP 1235
EP 1241
DI 10.1097/00006534-200110000-00021
PG 7
WC Surgery
SC Surgery
GA 479XJ
UT WOS:000171428900021
PM 11604625
ER

PT J
AU Wong, GB
   Mulliken, JB
   Benacerraf, BR
AF Wong, GB
   Mulliken, JB
   Benacerraf, BR
TI Prenatal sonographic diagnosis of major craniofacial anomalies
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Review
ID TREACHER-COLLINS-SYNDROME; SAETHRE-CHOTZEN SYNDROME; FETAL BIPARIETAL
   DIAMETER; DANDY-WALKER SYNDROME; APERT-SYNDROME; CROUZON SYNDROME;
   HEMIFACIAL MICROSOMIA; PFEIFFER-SYNDROME; MANDIBULOFACIAL DYSOSTOSIS;
   STICKLER SYNDROME
C1 Childrens Hosp, Div Plast Surg, Boston, MA 02115 USA.
   Childrens Hosp, Craniofacial Ctr, Boston, MA 02115 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA.
RP Mulliken, JB (reprint author), Childrens Hosp, Div Plast Surg, 300 Longwood Ave, Boston, MA 02115 USA.
NR 118
TC 11
Z9 11
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD OCT
PY 2001
VL 108
IS 5
BP 1316
EP 1333
DI 10.1097/00006534-200110000-00036
PG 18
WC Surgery
SC Surgery
GA 479XJ
UT WOS:000171428900036
PM 11604640
ER

PT J
AU Park, E
   Eaton, CA
   Goldstein, MG
   DePue, J
   Niaura, R
   Guadagnoli, E
   Gross, NM
   Dube, C
AF Park, E
   Eaton, CA
   Goldstein, MG
   DePue, J
   Niaura, R
   Guadagnoli, E
   Gross, NM
   Dube, C
TI The development of a decisional balance measure of physician smoking
   cessation interventions
SO PREVENTIVE MEDICINE
LA English
DT Article
DE physician; decisional balance; smoking cessation; counseling;
   motivation; primary care
ID PRIMARY-CARE; SMOKERS; MODEL; MAMMOGRAPHY; PREVENTION; BEHAVIORS;
   SERVICES; PATTERNS; CANCER; ADVICE
AB Background. Decreasing the prevalence of smoking is an important health care goal, and there is evidence that physicians' advice to quit is an important motivator for patients. However, fewer than half of smokers report that they have ever been advised to quit. This study was conducted to develop a decisional balance measure for physician delivery of smoking cessation interventions.
   Methods. This study included a convenience sample of 155 primary care physicians. A decisional balance measure was developed using item generation and development, pilot testing, and principal components analyses. Validity was established by relating the deci-sional balance measure to a previously validated item of counseling behavior and to physician stage of readi-ness to deliver smoking cessation counseling.
   Results. Based on principal components analyses and item analyses, the final measure consisted of 10 Pro and 10 Con items with coefficient a of 0.83 and 0.86. The Pros and Cons scales were significantly associated with self-reported counseling to patients who smoke and to stage of readiness to deliver smoking cessation counseling.
   Conclusions. A decisional balance measure of physician smoking cessation interventions can be used to assist investigators in developing effective interventions to enhance the delivery of smoking cessation interventions in primary care settings. (C) 2001 American Health Foundation and Academic Press.
C1 Brown Univ, Sch Med, Ctr Behav & Prevent Med, Providence, RI 02912 USA.
   Brown Univ, Miriam Hosp, Ctr Behav & Prevent Med, Providence, RI 02912 USA.
   Bayer Inst Hlth Care Commun, Clin Educ & Res, Boston, MA USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Park, E (reprint author), Massachusetts Gen Hosp, 50 Staniford St,Room 904A, Boston, MA 02114 USA.
FU NCI NIH HHS [P01CA50087]
NR 44
TC 24
Z9 24
U1 1
U2 2
PU ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
J9 PREV MED
JI Prev. Med.
PD OCT
PY 2001
VL 33
IS 4
BP 261
EP 267
DI 10.1006/pmed.2001.0879
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 477JC
UT WOS:000171279500005
PM 11570829
ER

PT J
AU Simon, NM
   Sharma, SG
   Worthington, JJ
   Marzol, PC
   Pollack, MH
AF Simon, NM
   Sharma, SG
   Worthington, JJ
   Marzol, PC
   Pollack, MH
TI Citalopram for social phobia: A clinical case series
SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE citalopram; social anxiety; social phobia
ID ANXIETY DISORDER
AB 1. Social anxiety disorder is a common illness with significant associated disability. Serotonin selective reuptake inhibitors (SSRIs) have become first-line treatment given their improved tolerability; however, there are few reports on the use of citalopram.
   2. Nine consecutive patients with a primary diagnosis of DSM-IV generalized social phobia were prospectively treated with citalopram.
   3. Citalopram was generally well-tolerated, and seven patients achieved responder status.
   4. This series of patients improved significantly on all measures. Results suggest that citalopram may be a safe and effective treatment for social anxiety disorder.
C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA.
RP Simon, NM (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, 15 Parkman St,WAC 815, Boston, MA 02114 USA.
NR 17
TC 8
Z9 8
U1 4
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0278-5846
J9 PROG NEURO-PSYCHOPH
JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry
PD OCT
PY 2001
VL 25
IS 7
BP 1469
EP 1474
DI 10.1016/S0278-5846(01)00189-0
PG 6
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 458KY
UT WOS:000170194600011
PM 11513360
ER

PT J
AU Wulfkuhle, JD
   McLean, KC
   Paweletz, CP
   Sgroi, DC
   Trock, BJ
   Steeg, PS
   Petricoin, EF
AF Wulfkuhle, JD
   McLean, KC
   Paweletz, CP
   Sgroi, DC
   Trock, BJ
   Steeg, PS
   Petricoin, EF
TI New approaches to proteomic analysis of breast cancer
SO PROTEOMICS
LA English
DT Review
DE breast cancer; surface-enhanced laser desorption/ionization
   two-dimensional polyacrylamide gel electrophoresis; laser capture
   microdissection pharmacoproteomics; review
ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; LASER CAPTURE MICRODISSECTION;
   MAMMARY EPITHELIAL-CELLS; PROTEIN EXPRESSION; POLYPEPTIDE EXPRESSION;
   DUCTAL CARCINOMA; RISK; HYPERPLASIA; PROGRESSION; DISEASE
AB Proteomic based approaches are beginning to be utilized to study the natural history and treatment of breast cancer. A variety of proteomics approaches are under study, and are summarized herein. Two-dimensional gel electrophoresis (2D-PAGE) is still the foundation of most proteomics studies. We present an analysis of 2D-PAGE studies reported to date in breast cancer, including those examining normal/tumor differences and selected populations of breast cells. Newer technologies such as laser capture microdissection and highly sensitive mass spectrometry methods are currently being used together to identify greater numbers of lower abundance proteins that are differentially expressed between defined cell populations. Novel technologies still in developmental phases will enable identification of validated targets in small biopsy specimens, including high density protein arrays, antibody arrays and lysate arrays. Surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) analysis enables the high throughput characterization of lysates from very few tumor cells and may be best suited for clinical biomarker studies. We present SELDI-TOF data herein to show the accuracy of the method in a small cohort of breast tumors, as well as its potential discriminatory capability. Such technologies are expected to supplement our armamentarium of mRNA-based assays, and provide critical information on protein levels and post-translational modifications.
C1 US FDA, NCI,CBER, Div Therapeut Prod, Clin Proteom Program, Bethesda, MD 20892 USA.
   NCI, Canc Res Ctr, Pathol Lab, Womens Canc Sect, Bethesda, MD 20892 USA.
   NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA.
   Georgetown Univ, Dept Chem, Washington, DC 20057 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA.
   Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA.
RP Petricoin, EF (reprint author), US FDA, NCI,CBER, Div Therapeut Prod, Clin Proteom Program, Bldg 29A,Room 2B02,8800 Rockville Pike, Bethesda, MD 20892 USA.
NR 62
TC 151
Z9 154
U1 1
U2 13
PU WILEY-V C H VERLAG GMBH
PI BERLIN
PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY
SN 1615-9853
J9 PROTEOMICS
JI Proteomics
PD OCT
PY 2001
VL 1
IS 10
BP 1205
EP 1215
DI 10.1002/1615-9861(200110)1:10<1205::AID-PROT1205>3.3.CO;2-O
PG 11
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 486WF
UT WOS:000171839400004
PM 11721633
ER

PT J
AU Petersen, T
   Gordon, JA
   Kant, A
   Fava, M
   Rosenbaum, JF
   Nierenberg, AA
AF Petersen, T
   Gordon, JA
   Kant, A
   Fava, M
   Rosenbaum, JF
   Nierenberg, AA
TI Treatment resistant depression and Axis I co-morbidity
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
ID ANTIDEPRESSANT RESPONSE; REFRACTORY DEPRESSION; SEROTONERGIC FUNCTION;
   MAJOR DEPRESSION; DRUG RESPONSE; PREDICTORS; IMIPRAMINE; UNIPOLAR
AB Background. Treatment resistant depression (TRD) continues to present a formidable challenge to clinicians, accounts for over half of the annual costs associated with treatment for depression and causes great frustration to patients. Although there have been studies attempting to define TRD, little information is available as to the cause of TRD. One suggestion is that patients with TRD have a greater frequency of co-morbid psychiatric disorders, which explains their resistance to standard antidepressant treatments. The objective of this study was to compare the co-morbidity of Axis I disorders between a sample of TRD patients and a sample of non-TRD patients.
   Methods. TRD and non-TRD patients, recruited from two separate antidepressant treatment studies, were assessed for Axis I co-morbidity using the SCID-P for the DSM-III-R. Patients for the two samples were then matched for baseline HAM-D-17 total score and gender.
   Results. Results reveal that non-TRD patients had a higher rate of both lifetime and current generalized anxiety disorder co-morbidity than did the TRD patients. No other statistically significant differences in Axis I co-morbidity were found.
   Conclusions. These findings do not support the idea that current or lifetime Axis I co-morbidity is more common in TRD than non-TRD patients. In fact, the only statistical difference showed non-TRD patients with higher co-morbidity rates.
C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA.
RP Petersen, T (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA.
FU NIMH NIH HHS [R01-MH48483, R29-MH46952]
NR 30
TC 37
Z9 38
U1 0
U2 2
PU CAMBRIDGE UNIV PRESS
PI PORT CHESTER
PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA
SN 0033-2917
J9 PSYCHOL MED
JI Psychol. Med.
PD OCT
PY 2001
VL 31
IS 7
BP 1223
EP 1229
PG 7
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 484AV
UT WOS:000171668800009
PM 11681548
ER

PT J
AU Leszczynski, D
   Pitsillides, CM
   Pastila, RK
   Anderson, RR
   Lin, CP
AF Leszczynski, D
   Pitsillides, CM
   Pastila, RK
   Anderson, RR
   Lin, CP
TI Laser-beam-triggered microcavitation: A novel method for selective cell
   destruction
SO RADIATION RESEARCH
LA English
DT Article
ID TUMOR VASCULATURE; OXIDATIVE STRESS; CATHEPSIN-D; APOPTOSIS;
   ANGIOGENESIS; PROTEASES; INHIBITOR; AUTOIMMUNITY; ABSORPTION; RADIATION
AB We describe a new method of cell destruction that may have potential for use in antitumor therapy. Cells are loaded by phagocytosis with microparticles (<1 pm) and irradiated with short laser pulses. Absorption of laser energy by the microparticles causes localized vaporization of the fluid surrounding the microparticles, leading to the generation of transient vapor bubbles (microcavitation) around the microparticles. Using cultures of bovine aortic endothelial cells, we demonstrate that induction of intralysosomal microcavitation is an efficient, rapid and selective method of cell killing that is dependent on the number of microparticles, the number of laser pulses, and the fluence of the laser pulses. Cell killing by microcavitation is a very selective process that is restricted to cells containing microparticles, leaving other cells unaffected. Intracytoplasmic release of lysosomal hydrolases is, in part, responsible for cell death, because the protease inhibitors E64d and TLCK diminished cell killing. Using the broad-specificity caspase inhibitor Z-VAD-fmk, we determined that lysosomal hydrolases could induce apoptosis in a caspase-independent manner. We also examined the possibility of microcavitation-induced delayed effects in the cells that survived the treatment. Using flow cytometry, we determined that there was no delayed cell death between 1 and 4 days after microcavitation. Moreover, we did not observe changes in the cell cycle, in expression of the proteins BCL2, HSP70 and HSP27, or in PARP degradation. In conclusion, microcavitation induces rapid and specific cells death (limited only to cells containing microparticles), without producing delayed effects mong the surviving cells. (C) 2001 by Radiation Research Society
C1 STUK, Radiat & Nucl Safety Author, Dept Res & Environm Surveillance, Bio NIR Res Grp,Lab Radiobiol, FIN-00880 Helsinki, Finland.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA.
RP Leszczynski, D (reprint author), STUK, Radiat & Nucl Safety Author, Dept Res & Environm Surveillance, Bio NIR Res Grp,Lab Radiobiol, Laippatie 4, FIN-00880 Helsinki, Finland.
NR 25
TC 36
Z9 36
U1 0
U2 3
PU RADIATION RESEARCH SOC
PI OAK BROOK
PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD OCT
PY 2001
VL 156
IS 4
BP 399
EP 407
DI 10.1667/0033-7587(2001)156[0399:LBTMAN]2.0.CO;2
PG 9
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
   Nuclear Medicine & Medical Imaging
GA 478DE
UT WOS:000171327000007
PM 11554851
ER

PT J
AU Michael, BD
   Held, KD
   Schettino, G
   Folkard, M
   Prise, KM
   Vojnovic, B
AF Michael, BD
   Held, KD
   Schettino, G
   Folkard, M
   Prise, KM
   Vojnovic, B
TI Charged-particle and focused soft X-ray microbeams for investigating
   individual and collective radiation responses of cells
SO RADIATION RESEARCH
LA English
DT Meeting Abstract
C1 Mt Vernon Hosp, Gray Lab, Northwood HA6 2JR, Middx, England.
   Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RI Prise, Kevin/N-7872-2015
OI Prise, Kevin/0000-0001-6134-7946
NR 0
TC 2
Z9 3
U1 0
U2 0
PU RADIATION RESEARCH SOC
PI OAK BROOK
PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA
SN 0033-7587
J9 RADIAT RES
JI Radiat. Res.
PD OCT
PY 2001
VL 156
IS 4
BP 439
EP 440
PG 2
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
   Nuclear Medicine & Medical Imaging
GA 478DE
UT WOS:000171327000020
ER

PT J
AU Copen, WA
   Schwamm, LH
   Gonzalez, RG
   Wu, O
   Harmath, CB
   Schaefer, PW
   Koroshetz, WJ
   Sorensen, AG
AF Copen, WA
   Schwamm, LH
   Gonzalez, RG
   Wu, O
   Harmath, CB
   Schaefer, PW
   Koroshetz, WJ
   Sorensen, AG
TI Ischemic stroke: Effects of etiology and patient age on the time course
   of the core apparent diffusion coefficient
SO RADIOLOGY
LA English
DT Article
DE aging; brain, diffusion; brain, infarction; brain, MR; magnetic
   resonance (MR), diffusion study
ID FOCAL CEREBRAL-ISCHEMIA; NEONATAL RAT-BRAIN; WEIGHTED MRI;
   COPENHAGEN-STROKE; HYPERACUTE STROKE; WATER DIFFUSION; GLOBAL-ISCHEMIA;
   VOLUME; EVOLUTION; INJURY
AB PURPOSE: To determine whether the evolution of the core apparent diffusion coefficient (ADC) of water in ischemic stroke varies with patient age or infarct etiology.
   MATERIALS AND METHODS: One hundred forty-seven patients with stroke underwent 236 diffusion-weighted magnetic resonance imaging examinations. Etiologies of lesions were classified according to predefined criteria; in 224 images, the diagnosis of lacune could be firmly established or excluded. ADC was measured in the center of each lesion and in contralateral normal-appearing brain. A model was used to describe the time course of relative ADC (rADC), which is calculated by dividing the lesion ADC by the contralateral ADC, and to test for age- or etiology-related differences in this time course.
   RESULTS: Transition from decreasing to increasing rADC was estimated at 18.5 hours after stroke onset. In subgroup analysis, transition was earlier in nonlacunes than in lacunes (P =.02). There was a trend toward earlier transition in patients older than the median age of 66.0 years, compared with younger patients (P =.06). Pseudonormalization was estimated at 216 hours. Among nonlacunes, the rate of subsequent rADC increase was more rapid in younger patients than in older patients (P =.001). Within the smaller sample of lacunes, however, no significant age-related difference in this rate was found.
   CONCLUSION: Differences in ADC depending on the patient's age and infarct etiology suggest differing rates of ADC progression.
C1 Harvard Univ, Sch Med, Boston, MA 02129 USA.
   Massachusetts Gen Hosp, Div Neuroradiol, NMR Ctr, Dept Neurol, Boston, MA 02129 USA.
RP Sorensen, AG (reprint author), Harvard Univ, Sch Med, 13th St,Bldg 149,Mail Code 2301, Boston, MA 02129 USA.
OI Schwamm, Lee/0000-0003-0592-9145
FU NCRR NIH HHS [5P41-RR14075]; NINDS NIH HHS [R01NS8477-01]
NR 44
TC 62
Z9 64
U1 0
U2 3
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD OCT
PY 2001
VL 221
IS 1
BP 27
EP 34
DI 10.1148/radiol.2211001397
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 474QT
UT WOS:000171118900006
PM 11568317
ER

PT J
AU Grant, PE
   He, J
   Halpern, EF
   Wu, O
   Schaefer, PW
   Schwamm, LH
   Budzik, RF
   Sorensen, AG
   Koroshetz, WJ
   Gonzalez, RG
AF Grant, PE
   He, J
   Halpern, EF
   Wu, O
   Schaefer, PW
   Schwamm, LH
   Budzik, RF
   Sorensen, AG
   Koroshetz, WJ
   Gonzalez, RG
TI Frequency and clinical context of decreased apparent diffusion
   coefficient reversal in the human brain
SO RADIOLOGY
LA English
DT Article
DE brain, infarction; magnetic resonance (MR), diffusion study
ID ISCHEMIC RAT-BRAIN; TRANSIENT GLOBAL AMNESIA; FOCAL CEREBRAL-ISCHEMIA;
   ACUTE STROKE; WEIGHTED MR; STATUS EPILEPTICUS; SIGNAL INTENSITY;
   RESONANCE; PERFUSION; INJURY
AB PURPOSE: To determine the probability that regions of decreased apparent diffusion coefficient (ADC) return to normal without persistent symptoms or T2 change and the settings in which these ADC reversals occur.
   MATERIALS AND METHODS: Three hundred magnetic resonance (MR) imaging studies were selected at random from a database of 7,147 examinations to determine the probability of a pathologically decreased ADC. In cases with decreased ADC, the clinical history was recorded and, if available, follow-up MR imaging findings were evaluated. Five cases of ADC reversal became known during the same period and were evaluated to determine the initial ADC decrease, clinical outcome, and findings at follow-up imaging.
   RESULTS: Findings in 116 of 300 MR imaging studies revealed regions of decreased ADC. In 49 of 116 studies, follow-up MR imaging examinations were performed at least 4 weeks after the onset of symptoms; ADC did not reverse. Five cases of ADC reversal were identified in the same period, giving an estimated 0.2%-0.4% probability of ADC reversal. Clinical settings were venous sinus thrombosis and seizure (n = 3), hemiplegic migraine (n = 1), and hyperacute arterial infarction (n = 1). Both white matter (n = 3) and gray matter (n = 3) regions were involved.
   CONCLUSION: Reversal of ADC lesions is rare, occurs in complicated clinical settings, and can involve white or gray matter.
C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Grant, PE (reprint author), Massachusetts Gen Hosp, Dept Radiol, Gray 2,Rm B285,55 Fruit St, Boston, MA 02114 USA.
OI Schwamm, Lee/0000-0003-0592-9145
FU NCI NIH HHS [CA83159]; NCRR NIH HHS [RR13213]; NINDS NIH HHS [NS3462,
   R01NS8477-01]
NR 42
TC 77
Z9 78
U1 0
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD OCT
PY 2001
VL 221
IS 1
BP 43
EP 50
DI 10.1148/radiol.2211001523
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 474QT
UT WOS:000171118900008
PM 11568319
ER

PT J
AU McMahon, PM
   Halpern, EF
   Fernandez-del Castillo, C
   Clark, JW
   Gazelle, GS
AF McMahon, PM
   Halpern, EF
   Fernandez-del Castillo, C
   Clark, JW
   Gazelle, GS
TI Pancreatic cancer: Cost-effectiveness of imaging technologies for
   assessing resectability
SO RADIOLOGY
LA English
DT Article
DE cost-effectiveness; pancreas; neoplasms; radiology and radiologists,
   socioeconomic issues
ID MAGNETIC-RESONANCE; CONSECUTIVE PANCREATICODUODENECTOMIES; LAPAROSCOPIC
   ULTRASONOGRAPHY; BILIARY DRAINAGE; RANDOMIZED-TRIAL; HELICAL CT;
   CARCINOMA; SURVIVAL; TUMOR; DIAGNOSIS
AB PURPOSE: To evaluate the cost-effectiveness of imaging strategies for the assessment of resectability in patients with pancreatic cancer.
   MATERIALS AND METHODS: A decision model was developed to calculate costs and benefits (survival) accruing to hypothetical cohorts of patients with known or suspected pancreatic cancer. Results are presented as cost per life-year gained under various scenarios and assumptions of diagnostic test characteristics, surgical mortality, disease characteristics, and costs.
   RESULTS: With best estimates for all data inputs, the strategy of computed tomography (CT) followed by laparoscopy and laparoscopic ultrasonography (US) had an incremental cost-effectiveness ratio of $87,502 per life-year gained, compared with best supportive care. This strategy was significantly more cost-effective than CT followed by magnetic resonance (MR) imaging and was significantly less expensive than other imaging strategies while providing a statistically and clinically insignificant difference in life-year gains. A strategy involving no imaging (immediate surgery) was more expensive but less effective than all imaging strategies. A hypothetical perfect test with cost equal to that of CT followed by MR had an incremental cost-effectiveness ratio of $64,401 per life-year gained, compared to best supportive care.
   CONCLUSION: Most available imaging tests for assessing resectability of pancreatic cancer do not differ in effectiveness, but a strategy of CT, laparoscopy, and laparoscopic US would consistently result in significantly lower costs than other imaging tests under a wide range of scenarios.
C1 Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Oncol, Boston, MA 02114 USA.
   Harvard Univ, Program Hlth Policy, Cambridge, MA 02138 USA.
   Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Zero Emerson Pl,Suite 2H, Boston, MA 02114 USA.
EM scott@the-data-group.org
NR 79
TC 28
Z9 34
U1 0
U2 0
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD OCT
PY 2001
VL 221
IS 1
BP 93
EP 106
DI 10.1148/radiol.2211001656
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 474QT
UT WOS:000171118900015
PM 11568326
ER

PT J
AU Muradin, GSR
   Bosch, JL
   Stijnen, T
   Hunink, MGM
AF Muradin, GSR
   Bosch, JL
   Stijnen, T
   Hunink, MGM
TI Balloon dilation and stent implantation for treatment of femoropopliteal
   arterial disease: Meta-analysis
SO RADIOLOGY
LA English
DT Article; Proceedings Paper
CT 86th Scientific Assembly and Annual Meeting of the
   Radiological-Society-of-North-America (RSNA)
CY NOV 26-DEC 01, 2000
CL CHICAGO, ILLINOIS
SP Radiol Soc N Amer
DE arteries, femoral; arteries, grafts and prostheses; arteries, popliteal;
   arteries, stenosis or obstruction; arteries, transluminal angioplasty;
   radiology and radiologists, outcomes studies; stents and prostheses
ID SUPERFICIAL FEMORAL-ARTERY; PERCUTANEOUS TRANSLUMINAL ANGIOPLASTY;
   FOLLOW-UP; PALMAZ STENT; POPLITEAL ARTERIES; OCCLUSIVE LESIONS;
   ISCHEMIA; PATENCY; REVASCULARIZATION; ATHERECTOMY
AB PURPOSE: To perform a meta-analysis of long-term results of balloon dilation and stent implantation in the treatment of femoropopliteal arterial disease.
   MATERIALS AND METHODS: The English-language literature was searched for studies published between 1993 and 2000. Inclusion criteria for articles were presentation of long-term primary patency rates, standard errors (explicitly reported or derivable), and baseline characteristics of the study population. Two reviewers independently able) extracted data, and discrepancies were resolved by consensus. Primary patency rates were combined by using a technique that allows adjustment for differences across study populations. Analyses were adjusted for lesion type and clinical indication.
   RESULTS: Nineteen studies met the inclusion criteria, representing 923 balloon dilations and 473 stent implantations. Combined 3-year patency rates after balloon dilation were 61% (standard error, 2.2% for stenoses and claudication, 48% (standard error, 3.3%) for occlusions and claudication, 43% (standard error, 4.1%) for stenoses and critical ischemia, and 30% (standard error, 3.7%) for occlusions and critical ischemia. The 3-year patency rates after stent implantation were 63%-66% (standard error, 4.1%) and were independent of clinical indication and lesion type. Funnel plots demonstrated an asymmetric distribution of the data points associated with stent studied.
   CONCLUSION: Balloon dilation and stent implantation for claudication and stenosis yield similar long-term patency rates. For more severe femoropopliteal disease, the results of stent implantation seem more favorable. Publication bias could not be ruled out.
C1 Erasmus Univ, Med Ctr Rotterdam, Dept Radiol, NL-3015 GE Rotterdam, Netherlands.
   Erasmus Univ, Med Ctr Rotterdam, Program Assessment Radiol Technol, NL-3015 GE Rotterdam, Netherlands.
   Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol & Biostat, NL-3015 GE Rotterdam, Netherlands.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA.
   Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Hunink, MGM (reprint author), Erasmus Univ, Med Ctr Rotterdam, Dept Radiol, Dr Molewaterpl 50,Rm EE21-40A, NL-3015 GE Rotterdam, Netherlands.
NR 35
TC 137
Z9 152
U1 0
U2 2
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD OCT
PY 2001
VL 221
IS 1
BP 137
EP 145
DI 10.1148/radiol.2211010039
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 474QT
UT WOS:000171118900019
PM 11568332
ER

PT J
AU Solbiati, L
   Livraghi, T
   Goldberg, SN
   Ierace, T
   Meloni, F
   Dellanoce, M
   Cova, L
   Halpern, EF
   Gazelle, GS
AF Solbiati, L
   Livraghi, T
   Goldberg, SN
   Ierace, T
   Meloni, F
   Dellanoce, M
   Cova, L
   Halpern, EF
   Gazelle, GS
TI Percutaneous radio-frequency ablation of hepatic metastases from
   colorectal cancer: Long-term results in 117 patients
SO RADIOLOGY
LA English
DT Article; Proceedings Paper
CT 86th Scientific Assembly and Annual Meeting of the
   Radiological-Society-of-North-America (RSNA)
CY NOV 26-DEC 01, 2000
CL CHICAGO, ILLINOIS
SP Radiol Soc N Amer
DE liver neoplasms, secondary; liver neoplasms, therapy; radiofrequency
   (RF) ablation
ID RADIOFREQUENCY TISSUE ABLATION; PERIOPERATIVE BLOOD-TRANSFUSION;
   UNTREATED LIVER METASTASES; CARCINOMA METASTASES; NATURAL-HISTORY;
   THERMAL ABLATION; RESECTION; SURVIVAL; EXPERIENCE; ELECTRODE
AB PURPOSE: To describe the results of an ongoing radio-frequency (RF) ablation study in patients with hepatic metastases from colorectal carcinoma.
   MATERIALS AND METHODS: In 117 patients, 179 metachronous colorectal carcinoma hepatic metastases (0.9-9.6 cm in diameter) were treated with RF ablation by using 17-gauge internally cooled electrodes. Computed, tomographic follow-up was performed every 4-6 months. Recurrent tumors were retreated when feasible. Time to new metastases and death for each patient and time to local recurrence for individual lesions were modeled with Kaplan-Meier analysis. Modeling determined the effect of number of metastases on the time to new metastases and death and effect of tumor size on local recurrence.
   RESULTS: Estimated median survival was 36 months (95% Cl; 28, 52 months). Estimated 1, 2, and 3-year survival rates were 93%, 69%, and 46%, respectively. Survival was not significantly related to number of metastases treated. In 77 (66%) of 117 patients, new metastases were observed at follow-up. Estimated median time until new metastases was 12 months (95% Cl; 10, 18 months). Percentages of patients with no new metastases after initial treatment at 1 and 2 years were 49% and 35%, respectively. Time to new metastases was not significantly related to number of metastases. Seventy (39%) of 179 lesions developed local recurrence after treatment. Of these, 54 were observed by 6 months and 67 by 1 year. No local recurrence was observed after 18 months. Frequency and time to local recurrence were related to lesion size (P less than or equal to .001).
   CONCLUSION: RF ablation is an effective method to treat hepatic metastases from colorectal carcinoma.
C1 Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA.
   Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
   Osped Gen, Dept Radiol, Busto Arsizio, Italy.
   Osped Civile, Dept Radiol, Vimercate, Italy.
   Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA.
RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Zero Emerson Pl,Suite 2H, Boston, MA 02114 USA.
OI meloni, maria franca/0000-0001-7485-7400; Solbiati,
   Luigi/0000-0002-3109-1449
NR 72
TC 593
Z9 627
U1 4
U2 21
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD OCT
PY 2001
VL 221
IS 1
BP 159
EP 166
DI 10.1148/radiol.2211001624
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 474QT
UT WOS:000171118900021
PM 11568334
ER

PT J
AU Bureau, NJ
   Kaplan, PA
   Dussault, RG
AF Bureau, NJ
   Kaplan, PA
   Dussault, RG
TI Lumbar facet joint synovial cyst: Percutaneous treatment with steroid
   injections and distention - Clinical and imaging follow-up in 12
   patients
SO RADIOLOGY
LA English
DT Article; Proceedings Paper
CT 86th Scientific Assembly and Annual Meeting of the
   Radiological-Society-of-North-America (RSNA)
CY NOV 26-DEC 01, 2000
CL CHICAGO, ILLINOIS
SP Radiol Soc N Amer
DE computed tomography (CT), guidance; spine, cysts; spine, facet joints;
   spine, interventional procedure; steroids
ID NERVE ROOT COMPRESSION; 10-YEAR EXPERIENCE; DIAGNOSIS; SPINE
AB PURPOSE: To determine the imaging characteristics of lumbar facet joint synovial cysts after percutaneous treatment with steroid injections and distention of the cyst and to correlate these findings with the clinical outcome.
   MATERIALS AND METHODS: Clinical outcome and imaging findings were retrospectively studied in 12 patients (four men, eight women) aged 45-79 years (mean, 60 years) with a symptomatic lumbar facet joint synovial cyst treated with percutaneous steroid injections. At varying times after the procedure, patients were contacted for clinical follow-up, and repeat imaging was performed to verify the status of the cyst.
   RESULTS: Excellent pain relief was achieved in nine (75%) of 12 patients. At follow-up imaging, the cyst completely regressed in six (67%) of these nine patients, partially regressed in two (22%) patients, and was unchanged in one (11%) patient. One (8%) of the 12 patients had transient pain relief, with recurrence of symptoms at short intervals after each of three injections. No pain relief was achieved in two (17%) of 12 patients.
   CONCLUSION: Image-guided percutaneous steroid injections are often effective in the treatment of lumbar facet joint synovial cysts and may result in complete regression of the cyst.
C1 Univ Montreal, Hop St Luc, Ctr Hosp, Dept Radiol, Montreal, PQ H2X 3J4, Canada.
   Massachusetts Gen Hosp, Dept Bone & Joint Radiol, Boston, MA 02114 USA.
RP Bureau, NJ (reprint author), Univ Montreal, Hop St Luc, Ctr Hosp, Dept Radiol, 1058 St Denis St, Montreal, PQ H2X 3J4, Canada.
RI Bureau, Nathalie/G-1506-2015
OI Bureau, Nathalie/0000-0003-3710-9280
NR 25
TC 48
Z9 49
U1 0
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD OCT
PY 2001
VL 221
IS 1
BP 179
EP 185
DI 10.1148/radiol.2211010213
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 474QT
UT WOS:000171118900024
PM 11568337
ER

PT J
AU Moore, A
   Josephson, L
   Bhorade, RM
   Basilion, JP
   Weissleder, R
AF Moore, A
   Josephson, L
   Bhorade, RM
   Basilion, JP
   Weissleder, R
TI Human transferrin receptor gene as a marker gene for MR imaging
SO RADIOLOGY
LA English
DT Article
DE experimental study; neoplasms, experimental studies; neoplasms,
   radionuclide studies; genes and genetics
ID VIRUS THYMIDINE KINASE; SODIUM/IODIDE SYMPORTER GENE;
   POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; CONTRAST AGENT;
   ASIALOGLYCOPROTEIN RECEPTORS; ADENOVIRAL VECTOR; THERAPY MODEL;
   EXPRESSION; REPORTER
AB PURPOSE: To quantitate and characterize the expression of an engineered human transferrin receptor (ETR) as a marker gene by using magnetic resonance (MR) imaging.
   MATERIALS AND METHODS: Rat gliosarcoma 9L cells stably expressing ETR (ETR+) were used, with nontransfected (ETR-) cells serving as controls. A conjugate of transferrin and monocrystalline iron oxide (Tf-MION) nanoparticles was synthesized to probe for the activity of ETR. Accumulation of Tf-MION was examined by using cell internalization in culture and MR (n = 6) and nuclear (n = 4) imaging in a mouse model with ETR+ and ETR- tumors implanted in the opposite flanks. Autoradiographic and histopathologic results were correlated with MR findings.
   RESULTS: Tf-MION was internalized by ETR+ cells at 37 degreesC but not at 4 degreesC. Rhodamine-labeled Tf-MION and fluorescein-labeled antibody to ETR colocalized in small vesicle-like structures in the cytoplasm. Both findings were consistent with accumulation by the receptor-mediated endocytosis mechanism of ETR. Compared with ETR- tumors, ETR+ tumors accumulated more Tf-MION and had higher signal intensity on T1-weighted MR images and lower signal intensity on T2-weighted images. Autoradiographic findings showed a spatial correlation between MR signal intensity and TF-MION accumulation.
   CONCLUSION: ETR+ tumors internalize the MR imaging probe through the action of transferrin receptor in amounts that can be detected with MR imaging.
C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Moore, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Bldg 149,13th St,Rm 5419, Charlestown, MA 02129 USA.
NR 42
TC 114
Z9 125
U1 1
U2 8
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD OCT
PY 2001
VL 221
IS 1
BP 244
EP 250
DI 10.1148/radiol.2211001784
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 474QT
UT WOS:000171118900034
PM 11568347
ER

PT J
AU Sorensen, G
AF Sorensen, G
TI Worksite tobacco control programs: the role of occupational health
SO RESPIRATION PHYSIOLOGY
LA English
DT Article; Proceedings Paper
CT Conference on Susceptibility Factors for Respiratory Diseases
CY OCT 03-06, 2000
CL SANTA FE, NEW MEXICO
SP Lovelace Respiratory Res Inst
DE control; worksite smoking; health; tobacco smoke; worksite control;
   mammals; humans; tobacco; worksite control
ID WHITE-COLLAR WORKERS; PROMOTION PROGRAMS; CIGARETTE-SMOKING; WELLWORKS
   PROJECT; CANCER PREVENTION; WORKPLACE; INTERVENTION; PROTECTION;
   COMMUNITY; BEHAVIOR
AB Worksite tobacco control initiatives face a crucial challenge: the growing occupational disparity in smoking prevalence. Blue-collar workers are more likely to be smokers than workers are in white-collar jobs. Blue-collar workers also experience a high prevalence of hazardous exposures on the job. Given these multiple risks, it is imperative that successful comprehensive programs be developed to promote and protect the health of blue-collar workers. Although evidence is still accruing about the efficacy of workplace interventions integrating tobacco control and occupational health, it is possible to identify promising intervention strategies by drawing on the preliminary evidence on effective worksite interventions. The effectiveness of worksite tobacco control interventions will be enhanced when coordinated interventions aim to promote cessation among individual smokers, build social support for quitting and social norms that support non-smoking, engage management in assuring a healthy work environment, involve workers' families in non-smoking initiatives, and provide links to community and public policy initiatives that support tobacco control as well as a broader effort promoting worker health. (C) 2001 Elsevier Science B.V. All rights reserved.
C1 Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP Sorensen, G (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, 677 Huntington Ave, Boston, MA 02115 USA.
FU NCI NIH HHS [1 PO1 CA75308, 5 RO1 CA68087]; NIOSH CDC HHS [R01 OH04012]
NR 65
TC 15
Z9 16
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0034-5687
J9 RESP PHYSIOL
JI Respir. Physiol.
PD OCT
PY 2001
VL 128
IS 1
BP 89
EP 102
DI 10.1016/S0034-5687(01)00268-7
PG 14
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 477LB
UT WOS:000171284100012
PM 11535266
ER

PT J
AU Griffin, J
AF Griffin, J
TI The biology of signal transduction inhibition: Basic science to novel
   therapies
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID TYROSINE KINASE INHIBITOR; HEMATOPOIETIC-CELL LINES; ABL-POSITIVE CELLS;
   BCR-ABL; C-KIT; LEUKEMIA-CELLS; IN-VITRO; GROWTH; PROTEIN; STI571
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP Griffin, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA.
NR 22
TC 54
Z9 56
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 OCT
PY 2001
VL 28
IS 5
SU 17
BP 3
EP 8
DI 10.1053/sonc.2001.29182
PG 6
WC Oncology
SC Oncology
GA 501EZ
UT WOS:000172670900002
PM 11740801
ER

PT J
AU Schneider, JW
   Chang, AY
   Rocco, TP
AF Schneider, JW
   Chang, AY
   Rocco, TP
TI Cardiotoxicity in signal transduction therapeutics: ErbB2 antibodies and
   the heart
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID HUMAN-BREAST-CANCER; TRASTUZUMAB HERCEPTIN; NEUREGULIN RECEPTOR; CARDIAC
   DEVELOPMENT; DOXORUBICIN; HYPERTROPHY; EXPRESSION; SURVIVAL; FAILURE;
   KINASES
C1 VA Boston Healthcare Syst, Dept Med, Div Cardiol, W Roxbury, MA 02132 USA.
   Harvard Univ, Sch Med, W Roxbury, MA USA.
   Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Schneider, JW (reprint author), VA Boston Healthcare Syst, Dept Med, Div Cardiol, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
NR 24
TC 47
Z9 49
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 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD OCT
PY 2001
VL 28
IS 5
SU 16
BP 18
EP 26
DI 10.1053/sonc.2001.28546
PG 9
WC Oncology
SC Oncology
GA 492JJ
UT WOS:000172164400004
PM 11706392
ER

PT J
AU Demetri, GD
AF Demetri, GD
TI Targeting c-kit mutations in solid tumors: Scientific rationale and
   novel therapeutic options
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID GASTROINTESTINAL STROMAL TUMORS; TYROSINE KINASE INHIBITOR;
   INTERSTITIAL-CELLS; IN-VITRO; RECEPTOR; LIGAND; CAJAL; LEIOMYOSARCOMAS;
   GROWTH; DOMAIN
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RP Demetri, GD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Suite G-530, Boston, MA 02115 USA.
NR 41
TC 126
Z9 130
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 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD OCT
PY 2001
VL 28
IS 5
SU 17
BP 19
EP 26
DI 10.1053/sonc.2001.29181
PG 8
WC Oncology
SC Oncology
GA 501EZ
UT WOS:000172670900004
PM 11740803
ER

PT J
AU George, D
AF George, D
TI Platelet-derived growth factor receptors: A therapeutic target in solid
   tumors
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID FACTOR-B CHAINS; PROSTATE-CANCER; TYROSINE KINASE; BETA-RECEPTOR;
   FACTOR-A; PDGF RECEPTORS; ALPHA-RECEPTOR; IN-VITRO; EXPRESSION; PROTEINS
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
RP George, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, 44 Binney St,Room D-1230, Boston, MA 02115 USA.
NR 32
TC 109
Z9 115
U1 1
U2 8
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 OCT
PY 2001
VL 28
IS 5
SU 17
BP 27
EP 33
DI 10.1053/sonc.2001.29185
PG 7
WC Oncology
SC Oncology
GA 501EZ
UT WOS:000172670900005
PM 11740804
ER

PT J
AU Monto, A
   Wright, TL
AF Monto, A
   Wright, TL
TI The epidemiology and prevention of hepatocellular carcinoma
SO SEMINARS IN ONCOLOGY
LA English
DT Review
ID HEPATITIS-C VIRUS; B SURFACE-ANTIGEN; TERM-FOLLOW-UP; RISK-FACTORS;
   LIVER-TRANSPLANTATION; POSITIVE PATIENTS; INTERFERON-ALPHA;
   RANDOMIZED-TRIAL; UNITED-STATES; CIRRHOSIS
C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
RP Monto, A (reprint author), San Francisco VA Med Ctr, Mailstop 111B,4150 Clement St, San Francisco, CA 94121 USA.
NR 66
TC 96
Z9 101
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0093-7754
J9 SEMIN ONCOL
JI Semin. Oncol.
PD OCT
PY 2001
VL 28
IS 5
BP 441
EP 449
DI 10.1053/sonc.2001.26947
PG 9
WC Oncology
SC Oncology
GA 480NM
UT WOS:000171467900002
PM 11685737
ER

PT J
AU Chmura, SJ
   Gupta, N
   Advani, SJ
   Kufe, DW
   Weichselbaum, RR
AF Chmura, SJ
   Gupta, N
   Advani, SJ
   Kufe, DW
   Weichselbaum, RR
TI Prospects for viral-based strategies enhancing the anti-tumor effects of
   ionizing radiation
SO SEMINARS IN RADIATION ONCOLOGY
LA English
DT Article
ID HERPES-SIMPLEX VIRUS; TYPE-1 THYMIDINE KINASE; SUICIDE GENE-THERAPY;
   MALIGNANT BRAIN-TUMORS; STRAND BREAK REPAIR; CELL LUNG-CANCER; PHASE-I
   TRIAL; HSV-TK GENE; P53 GENE; CYTOSINE DEAMINASE
C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA.
   Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA.
   Dana Farber Canc Inst, Div Canc Pharmacol, Boston, MA 02115 USA.
RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA.
NR 94
TC 6
Z9 8
U1 0
U2 0
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 1053-4296
J9 SEMIN RADIAT ONCOL
JI Semin. Radiat. Oncol.
PD OCT
PY 2001
VL 11
IS 4
BP 338
EP 345
DI 10.1053/srao.2001.26019
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 482DK
UT WOS:000171559400008
PM 11677658
ER

PT J
AU Rattner, DW
   Apelgren, KN
   Eubanks, WS
AF Rattner, DW
   Apelgren, KN
   Eubanks, WS
TI The need for training opportunities in advanced laparoscopic surgery -
   The residents' perspective
SO SURGICAL ENDOSCOPY-ULTRASOUND AND INTERVENTIONAL TECHNIQUES
LA English
DT Article
DE laparoscopic surgery; resident education; surgical fellowship; surgical
   training
ID LEARNING-CURVE; SPLENECTOMY; FELLOWSHIPS
AB Background: There is controversy regarding the amount of training necessary to safely perform advanced laparoscopic surgery. General surgical residency often provides only a low volume of advanced laparoscopic cases and there is growing interest in nonaccredited fellowships focused on laparoscopic surgery.
   Objective: To assess surgical residents' perception of the need for training in advanced laparoscopic surgery in addition to that provided in a standard general surgical residency.
   Methods: A 15-item questionnaire was mailed to 985 physicians who either were Society of American Gastrointestinal Endoscopic Surgeons (SAGES) candidate members or had attended a SAGES resident course in 1998 or 1999. For the purposes of the survey, laparoscopic Nissen fundoplication, laparoscopic herniorrhaphy, laparoscopic splenectomy, and laparoscopic colectomy were chosen as advanced procedures.
   Results: Of the 85 responses obtained, 81% were from respondents who were at the postgraduate fourth-year (PG4) level or higher. Furthermore, 58% of the respondents had taken a course in advanced laparoscopic surgery outside their residency program. The respondents believed that to perform the procedures safely and with confidence on entering practice, they needed to do at least eight each of the selected laparoscopic procedures. As reported, 45% of the respondents had performed three or fewer laparoscopic hernias; 60% had performed three or fewer laparoscopic Nissen fundoplications; 81% had performed three or fewer laparoscopic colectomies; and 86% had performed three or fewer splenectomies. Only 32% of the residents expected to perform more than 10 laparoscopic Nissen fundoplications, only 10% expected to perform more than 10 colectomies, and only 4% expected to perform more than 10 splenectomies before completing their residency. Many respondents (65%) said they would pursue an additional year of advanced laparoscopic training if it were available. In programs unaffiliated with a fellowship in advanced laparoscopic surgery, 65% of the residents were concerned that such a fellowship would interfere with residency training in laparoscopic surgery. In comparison, only 24% of the residents in programs affiliated with a fellowship in advanced laparoscopic surgery believed that the fellowship interfered with their training, whereas 47% of the residents in programs affiliated with a fellowship in advanced laparoscopic surgery thought that the fellowship had no impact on their training
   Conclusions: Residents clearly perceive a need for additional training in advanced laparoscopic surgery. Residents from programs without a laparoscopic fellowship are concerned about a negative impact on their experience from a laparoscopic fellow, but residents from programs with a laparoscopic fellowship are neutral about the impact of a fellow.
C1 Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA.
   Michigan State Univ, Sch Med, Dept Surg, Lansing, MI USA.
   Duke Univ, Sch Med, Dept Surg, Durham, NC USA.
RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA.
NR 19
TC 78
Z9 79
U1 1
U2 1
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0930-2794
J9 SURG ENDOSC-ULTRAS
JI Surg. Endosc.-Ultrason. Interv. Tech.
PD OCT
PY 2001
VL 15
IS 10
BP 1066
EP 1070
DI 10.1007/s004640080021
PG 5
WC Surgery
SC Surgery
GA 479NP
UT WOS:000171410700003
PM 11727071
ER

PT J
AU Holmes, LB
AF Holmes, LB
TI Looking for long-term effects from prenatal exposures to anticonvulsants
SO TERATOLOGY
LA English
DT Editorial Material
ID FETAL HYDANTOIN SYNDROME; MALE EPILEPTIC PATIENTS; WOMEN; MEDICATION;
   HORMONES; DRUGS
C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA.
RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA.
NR 17
TC 3
Z9 3
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 0040-3709
J9 TERATOLOGY
JI Teratology
PD OCT
PY 2001
VL 64
IS 4
BP 175
EP 176
DI 10.1002/tera.1061
PG 2
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA 477LA
UT WOS:000171284000001
PM 11598922
ER

PT J
AU Singh, N
   Weisler, SL
   Hershman, JM
AF Singh, N
   Weisler, SL
   Hershman, JM
TI The acute effect of calcium carbonate on the intestinal absorption of
   levothyroxine
SO THYROID
LA English
DT Article
ID ALUMINUM HYDROXIDE; THYROXINE; HYPOTHYROIDISM; THERAPY; SUCRALFATE;
   EFFICACY
AB To determine the acute effect of calcium, we measured levothyroxine absorption after ingestion of thyroxine (T4) with and without simultaneous ingestion of calcium (as calcium carbonate) in seven volunteers without thyroid disease. Serum total T-4, total triiodothyronine (T-3), free T-4, and thyrotropin (TSH) levels were measured after ingestion of 1,000 mug of levothyroxine on two separate visits at 4-week intervals: (1) levothyroxine alone and (2) levothyroxine together with 2.0 g of calcium as calcium carbonate. The amount of absorbed levothyroxine was calculated as the incremental rise in serum T-4 level during the first 6 hours multiplied by the volume of distribution for the hormone. When 1,000 mug of levothyroxine alone was given to subjects, the maximum average total T-4 absorption was 837 mug (83.7% of the dose ingested) at 120 minutes. When levothyroxine was coadministered with 2.0 g of calcium (as calcium carbonate), the maximum average T-4 absorption decreased to 579 mug (57.9% of the dose ingested) at 240 minutes. The total levothyroxine absorption over 6 hours was Significantly greater with thyroxine than that with thyroxine and calcium (p = 0.02). The administration of calcium and levothyroxine in these subjects was associated with a significant reduction in the peak increment in serum total T-4 (P = 0.02) and free T-4 levels (p = 0.03), as well as a significant reduction in the overall increment in serum total T-4 (p = 0.003), free T-4 (p = 0.002), and total T-3 levels (p = 0.01) over four time points (120 minutes, 240 minutes, 360 minutes, 1,440 minutes). In summary, this pharmacokinetic study in seven volunteers indicates that calcium carbonate acutely reduces T-4 absorption.
C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Endocrinol & Metab, Los Angeles, CA 90073 USA.
RP Singh, N (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Internal Med, 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
NR 23
TC 33
Z9 34
U1 1
U2 2
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 1050-7256
J9 THYROID
JI Thyroid
PD OCT
PY 2001
VL 11
IS 10
BP 967
EP 971
DI 10.1089/105072501753211046
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 486WB
UT WOS:000171839000011
PM 11716045
ER

PT J
AU Vonderheide, RH
AF Vonderheide, RH
TI From cancer genomics to cancer immunotherapy: toward second-generation
   tumor antigens (vol 22, pg 516, 2001)
SO TRENDS IN IMMUNOLOGY
LA English
DT Correction
C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Vonderheide, RH (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD OCT
PY 2001
VL 22
IS 10
BP 581
EP 581
PG 1
WC Immunology
SC Immunology
GA 485YM
UT WOS:000171791100015
ER

PT J
AU Koerner, FC
   Oyama, T
   Maluf, H
AF Koerner, FC
   Oyama, T
   Maluf, H
TI Morphological observations regarding the origins of atypical cystic
   lobules (low-grade clinging carcinoma of flat type)
SO VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY
LA English
DT Article
DE breast; ductal carcinoma in situ; lobule; cyst; pathogenesis
ID IN-SITU; MAMMARY EPITHELIUM; BREAST; ESTROGEN; CELLS; ACTIVATION;
   SNOUTS; LESION; GENE
AB This study seeks to define the morphological pathogenesis of a form of cystic transformation of lobules referred to as atypical cystic lobule or low-grade clinging carcinoma of flat type. We collected 25 examples that seem to represent the early stages in the formation of atypical cystic lobules and made a careful study of their morphology. Our observations indicate that this lesion arises from pre-existing, structurally normal terminal duct-lobular units and that it seems to develop by the direct transformation of indigenous luminal cells. The transformed cells first become evident in the small duct or terminal ductule, where they appear as slightly enlarged columnar cells containing atypical nuclei. In more advanced examples, these alterations affect all luminal cells of the terminal duct-lobular unit, but the cells of the terminal ductule continue to show more pronounced changes than the cells lining the acini. The atypical cells within the lobule do not seem to displace the normal acinar cells. Instead, the cells form a continuum, making it impossible to define the point at which atypical cells and normal cells meet. Within the small duct, however, the atypical epithelium comes to an abrupt halt as the duct courses towards the nipple. Considering these observations, we ascribe the formation of atypical cystic lobules to the accumulation of atypical cells in pre-existing terminal duct-lobular units.
C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   Gunma Univ, Sch Med, Gunma Univ Hosp, Pathol Lab,Dept Path 2, Gunma, Japan.
   Washington Univ, Sch Med, Barnes Hosp, Lauren V Ackerman Lab Pathol,Div Surg Pathol, St Louis, MO USA.
RP Koerner, FC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Fruit St, Boston, MA 02114 USA.
NR 15
TC 18
Z9 18
U1 0
U2 0
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0945-6317
J9 VIRCHOWS ARCH
JI Virchows Arch. Int. J. Pathol.
PD OCT
PY 2001
VL 439
IS 4
BP 523
EP 530
PG 8
WC Pathology
SC Pathology
GA 483AD
UT WOS:000171610800004
PM 11710639
ER

PT J
AU Rue, M
   Roque, M
   Sola, J
   Macia, M
AF Rue, M
   Roque, M
   Sola, J
   Macia, M
CA Working Grp Severtiy Measure Corpo
TI Probabilistic models of mortality for patients admitted in conventional
   hospital units
SO MEDICINA CLINICA
LA Spanish
DT Article
DE severity of illness index; quality of health care; outcome assessment;
   risk adjustment; logistic models
ID ACUTE PHYSIOLOGY; MPM-II; SEVERITY; CARE; INFORMATION; PNEUMONIA;
   ILLNESS; QUALITY; APACHE; SYSTEM
AB BACKGROUND: We have developed a tool to measure disease severity of patients hospitalized in conventional units in order to evaluate and compare the effectiveness and quality of health care in our setting.
   PATIENTS AND METHOD: A total of 2,274 adult patients admitted consecutively to inpatient units from the Medicine, Surgery and Orthopaedic Surgery, and Trauma Departments of the Corporacio Sanitaria Parc Tauli of Sabadell, Spain, between November 1, 1997 and September 30, 1998 were included. The following variables were collected: demographic data, previous health state, substance abuse, comorbidity prior to admission, characteristics of the admission, clinical parameters within the first 24 hours of admission, laboratory results and data from the Basic Minimum Data Set of hospital discharges. Multiple logistic regression analysis was used to develop mortality probability models during the hospital stay.
   RESULTS: The mortality probability model at admission (MPMHOS.O) contained 7 variables associated with mortality during hospital stay: age, urgent admission, chronic cardiac insufficiency, chronic respiratory insufficiency, chronic liver disease, neoplasm, and dementia syndrome. The mortality probability model at 24-48 hours from admission (MPMHOS.24) contained 9 variables: those included in the MPMHOS.O plus two statistically significant laboratory variables: hemoglobin and creatinine.
   CONCLUSIONS: Severity measures, in particular those presented in this study, can be helpful for the interpretation of hospital mortality rates and can guide mortality or quality committees at the time of investigating health care-related problems.
C1 Corp Sanitaria Parc Tauli, Barcelona, Spain.
RP Rue, M (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA.
RI Rue, Montserrat/B-5663-2009
OI Rue, Montserrat/0000-0002-7862-9365
NR 25
TC 6
Z9 6
U1 0
U2 1
PU EDICIONES DOYMA S/L
PI BARCELONA
PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN
SN 0025-7753
J9 MED CLIN-BARCELONA
JI Med. Clin.
PD SEP 29
PY 2001
VL 117
IS 9
BP 326
EP 331
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 480NZ
UT WOS:000171469200002
PM 11749903
ER

PT J
AU Faradji, RN
   Havari, E
   Chen, Q
   Gray, J
   Tornheim, K
   Corkey, BE
   Mulligan, RC
   Lipes, MA
AF Faradji, RN
   Havari, E
   Chen, Q
   Gray, J
   Tornheim, K
   Corkey, BE
   Mulligan, RC
   Lipes, MA
TI Glucose-induced toxicity in insulin-producing pituitary cells that
   coexpress GLUT2 and glucokinase - Implications for metabolic engineering
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID PANCREATIC BETA-CELL; NON-ISLET CELLS; TURBO DESIGN; EXPRESSION;
   SECRETION; GLYCOLYSIS; RELEASE; PHOSPHORYLATION; CYCLE; LIVER
AB We have shown that intermediate lobe (IL) pituitary cells can be engineered to produce sufficient amounts of insulin (ins) to cure diabetes in nonobese diabetic mice but, unlike transplanted islets, ILins cells evade immune attack. To confer glucose-sensing capabilities into these cells, they were further modified with recombinant adenoviruses to express high levels of GLUT2 and the beta -cell isoform of glucokinase (GK). Although expression of GLUT2 alone had negligible effects on glucose usage and lactate production, expression of GK alone resulted in similar to2-fold increase in glycolytic flux within the physiological (3-20 mM) glucose range. GLUT2/GK coexpression further increased glycolytic flux at 20 mM glucose but disproportionately increased flux at 3 mM glucose. Despite enhanced glycolytic fluxes, GLUT2/GK-coexpressing cells showed glucose dose-dependent accumulation of hexose phosphates, depletion of intracellular ATP, and severe apoptotic cell death. These studies demonstrate that glucose-sensing properties can be introduced into non-islet cells by the single expression of GK and that glucose responsiveness can be augmented by the coexpression of GLUT2. However, in the metabolic engineering of surrogate beta cells, it is critical that the levels of the components be closely optimized to ensure their physiological function and to avoid the deleterious consequences of glucose-induced toxicity.
C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA.
   Boston Univ, Med Ctr, Dept Biochem, Boston, MA 02118 USA.
   Boston Univ, Med Ctr, Obes Res Ctr, Boston, MA 02118 USA.
   Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02215 USA.
RP Lipes, MA (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Med, 1 Joslin Pl,Rm 495, Boston, MA 02215 USA.
FU NIDDK NIH HHS [DK53064, DK53281, DK35914]
NR 39
TC 20
Z9 21
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 SEP 28
PY 2001
VL 276
IS 39
BP 36695
EP 36702
DI 10.1074/jbc.M102542200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 475XF
UT WOS:000171194500085
PM 11443115
ER

PT J
AU Morra, M
   Simarro-Grande, M
   Martin, M
   Chen, ASI
   Lanyi, A
   Silander, O
   Calpe, S
   Davis, J
   Pawson, T
   Eck, MJ
   Sumegi, J
   Engel, P
   Li, SC
   Terhorst, C
AF Morra, M
   Simarro-Grande, M
   Martin, M
   Chen, ASI
   Lanyi, A
   Silander, O
   Calpe, S
   Davis, J
   Pawson, T
   Eck, MJ
   Sumegi, J
   Engel, P
   Li, SC
   Terhorst, C
TI Characterization of SH2D1A missense mutations identified in X-linked
   lymphoproliferative disease patients
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID EPSTEIN-BARR-VIRUS; T-CELL ACTIVATION; CUTTING EDGE; ENCODING GENE;
   PROTEIN SAP; RECEPTOR; SLAM; INFECTION; 2B4; EXPRESSION
AB X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency characterized by extreme susceptibility to Epstein-Barr virus. The XLP disease gene product SH2D1A (SAP) interacts via its SH2 domain with a motif (TIYXXV) present in the cytoplasmic tail of the cell-surface receptors CD150/SLAM, CD84, CD229/Ly-9, and CD244/2B4. Characteristically, the SH2D1A three-pronged interaction with Tyr(281) of CD150 can occur in absence of phosphorylation. Here we analyze the effect of SH2D1A protein missense mutations identified in 10 XLP families. Two sets of mutants were found: (i) mutants with a marked decreased protein half-life (e.g. Y7C, S28R, Q99P, P101L, V102G, and X129R) and (ii) mutants with structural changes that differently affect the interaction with the four receptors. In the second group, mutations that disrupt the interaction between the SH2D1A hydrophobic cleft and Val +3 of its binding motif (e.g. T68I) and mutations that interfere with the SH2D1A phosphotyrosine-binding pocket (e.g. C42W) abrogated SH2D1A binding to all four receptors. Surprisingly, a mutation in SH2D1A able to interfere with Thr -2 of the CD150 binding motif (mutant T53I) severely impaired non-phosphotyrosine interactions while preserving unaffected the binding of SH2D1A to phosphorylated CD150. Mutant T53I, however, did not bind to CD229 and CD224, suggesting that SH2D1A controls several critical signaling pathways in T and natural killer cells. Because no correlation is present between identified types of mutations and XLP patient clinical presentation, additional unidentified genetic or environmental factors must play a strong role in XLP disease manifestations.
C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
   Univ Barcelona, Fac Med, Dept Cellular Biol & Pathol, Barcelona 08036, Spain.
   Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA.
   Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
   Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5G 1X5, Canada.
   Univ Western Ontario, Fac Med & Dent, Dept Biochem, London, ON N6A 5C1, Canada.
RP Terhorst, C (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Immunol, RE-204,330 Brookline Ave, Boston, MA 02215 USA.
RI Pawson, Tony/E-4578-2013; Simarro, Maria/M-3947-2015; 
OI Simarro, Maria/0000-0001-8917-7328; Silander, Olin/0000-0003-4105-8316;
   Martin, Margarita/0000-0002-9245-4899
FU NIAID NIH HHS [P01-AI-35714]
NR 40
TC 54
Z9 59
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 SEP 28
PY 2001
VL 276
IS 39
BP 36809
EP 36816
DI 10.1074/jbc.M101305200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 475XF
UT WOS:000171194500100
PM 11477068
ER

PT J
AU Kim, M
   Sun, ZYJ
   Byron, O
   Campbell, G
   Wagner, G
   Wang, JH
   Reinherz, EL
AF Kim, M
   Sun, ZYJ
   Byron, O
   Campbell, G
   Wagner, G
   Wang, JH
   Reinherz, EL
TI Molecular dissection of the CD2-CD58 counter-receptor interface
   identifies CD2 Tyr86 and CD58 Lys34 residues as the functional "hot
   spot"
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
DE adhesion complexes; analytical ultracentrifugation; CD2-CD58; isothermal
   titration calorimetry; protein structure
ID T-CELL ACTIVATION; PROTEIN-PROTEIN RECOGNITION; CRYSTAL-STRUCTURE;
   ADHESION DOMAIN; GLYCOPROTEIN CD2; LIGAND; SURFACE; LFA-3; AFFINITY;
   RESOLUTION
AB The heterophilic CD2-CD58 adhesion interface contains interdigitating residues that impart high specificity and rapid binding kinetics. To define the hot spot of this counter-receptor interaction, we characterized CD2 adhesion domain variants harboring a single mutation of the central Tyr86 or of each amino acid residue forming a salt link/hydrogen bond. Alanine mutations at D31, D32 and K34 on the C strand and K43 and R48 on the C' strand reduce affinity for CD58 by 47-127-fold as measured by isothermal titration calorimetry. The Y86A mutant reduces affinity by similar to 1000-fold, whereas Y86F is virtually without effect, underscoring the importance of the phenyl ring rather than the hydroxyl moiety. The CD2CD58 crystal structure offers a detailed view of this kev functional epitope: CD2 D31 and D32 orient the side-chain of CD58 Kj4 such that CD2 Y86 makes hydrophobic contact with the extended aliphatic component of CD58 K34 between CD2 Y86 and CD58 F46. The elucidation of this hot spot provides a new target for rational design of immunosuppressive compounds and suggests a general approach for other receptors. (C) 2001 Academic Press.
C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Biol Chem, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA.
   Univ Glasgow, Inst Biomed & Life Sci, Div Infect & Immun, Glasgow G12 8QQ, Lanark, Scotland.
   Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
RP Wang, JH (reprint author), Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA.
FU NIAID NIH HHS [AI21226, AI37581]; NIGMS NIH HHS [GM56008]
NR 50
TC 37
Z9 38
U1 0
U2 2
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 SEP 28
PY 2001
VL 312
IS 4
BP 711
EP 720
DI 10.1006/jmbi.2001.4980
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 481TP
UT WOS:000171536600012
PM 11575926
ER

PT J
AU Downing, PE
   Jiang, YH
   Shuman, M
   Kanwisher, N
AF Downing, PE
   Jiang, YH
   Shuman, M
   Kanwisher, N
TI A cortical area selective for visual processing of the human body
SO SCIENCE
LA English
DT Article
ID TEMPORAL CORTEX; BIOLOGICAL MOTION; PERCEPTION; BRAIN; REPRESENTATION;
   RECOGNITION; OBJECTS; PARTS
AB Despite extensive evidence for regions of human visual cortex that respond selectively to faces, few studies have considered the cortical representation of the appearance of the rest of the human body. We present a series of functional magnetic resonance imaging (fMRI) studies revealing substantial evidence for a distinct cortical region in humans that responds selectively to images of the human body, as compared with a wide range of control stimuli. This region was found in the lateral occipitotemporal cortex in all subjects tested and apparently reflects a specialized neural system for the visual perception of the human body.
C1 Univ Wales, Ctr Cognit Neurosci, Sch Psychol, Bangor LL57 2AS, Gwynedd, Wales.
   MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA.
   Massachusetts Gen Hosp, Nucl Magnet Resonance Imaging Ctr, Charlestown, MA 02129 USA.
RP Downing, PE (reprint author), Univ Wales, Ctr Cognit Neurosci, Sch Psychol, Bangor LL57 2AS, Gwynedd, Wales.
NR 21
TC 947
Z9 956
U1 13
U2 57
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD SEP 28
PY 2001
VL 293
IS 5539
BP 2470
EP 2473
DI 10.1126/science.1063414
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PD
UT WOS:000171237200052
PM 11577239
ER

PT J
AU Woolf, CJ
AF Woolf, CJ
TI Patrick D. Wall (1925-2001) - Obituary
SO NATURE
LA English
DT Biographical-Item
C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St, Charlestown, MA 02129 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 27
PY 2001
VL 413
IS 6854
BP 378
EP 378
DI 10.1038/35096680
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 475UY
UT WOS:000171188700039
PM 11574873
ER

PT J
AU Hwang, I
   Sheen, J
AF Hwang, I
   Sheen, J
TI Two-component circuitry in Arabidopsis cytokinin signal transduction
SO NATURE
LA English
DT Article
ID 2-COMPONENT RESPONSE REGULATOR; MAP KINASE CASCADE; HISTIDINE KINASE;
   ASP PHOSPHORELAY; LEAF SENESCENCE; PROTEIN-KINASES; PLANTS; THALIANA;
   YEAST; TRANSFORMATION
AB Cytokinins are essential plant hormones that are involved in shoot meristem and leaf formation, cell division, chloroplast biogenesis and senescence. Although hybrid histidine protein kinases have been implicated in cytokinin perception in Arabidopsis, the action of histidine protein kinase receptors and the downstream signalling pathway has not been elucidated to date. Here we identify a eukaryotic two-component signalling circuit that initiates cytokinin signalling through distinct hybrid histidine protein kinase activities at the plasma membrane. Histidine phosphotransmitters act as signalling shuttles between the cytoplasm and nucleus in a cytokinin-dependent manner. The short signalling circuit reaches the nuclear target genes by enabling nuclear response regulators ARR1, ARR2 and ARR10 as transcription activators. The cytokinin-inducible ARR4, ARR5, ARR6 and ARR7 genes encode transcription repressors that mediate a negative feedback loop in cytokinin signalling. Ectopic expression in transgenic Arabidopsis of ARR2, the rate-limiting factor in the response to cytokinin, is sufficient to mimic cytokinin in promoting shoot meristem proliferation and leaf differentiation, and in delaying leaf senescence.
C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Sheen, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
NR 48
TC 462
Z9 504
U1 7
U2 55
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 27
PY 2001
VL 413
IS 6854
BP 383
EP 389
DI 10.1038/35096500
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 475UY
UT WOS:000171188700044
PM 11574878
ER

PT J
AU Smith, MR
   McGovern, FJ
   Zietman, AL
   Fallon, MA
   Hayden, DL
   Schoenfeld, DA
   Kantoff, PW
   Finkelstein, JS
AF Smith, MR
   McGovern, FJ
   Zietman, AL
   Fallon, MA
   Hayden, DL
   Schoenfeld, DA
   Kantoff, PW
   Finkelstein, JS
TI Pamidronate to prevent bone loss during androgen-deprivation therapy for
   prostate cancer.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MINERAL DENSITY; HORMONE AGONISTS; POSTMENOPAUSAL OSTEOPOROSIS;
   INTRAVENOUS PAMIDRONATE; MEN; FRACTURES; CARCINOMA; TRIAL; WOMEN;
   HYPOGONADISM
AB Background: Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer. We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist.
   Methods: In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks). Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography. Forty-one men completed the study.
   Results: In men treated with leuprolide alone, the mean (+/-SE) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine, 2.1+/-0.6 percent in the trochanter, and 1.8+/-0.4 percent in the total hip, and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent (P<0.001 for each comparison with the base-line value). In contrast, the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate. There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine (P<0.001), trochanter (P=0.003), total hip (P=0.005), and trabecular bone of the lumbar spine (P=0.02).
   Conclusions: Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist. (N Engl J Med 2001;345:948-55.) Copyright (C) 2001 Massachusetts Medical Society.
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Smith, MR (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA.
FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [K24 DK02759]
NR 29
TC 431
Z9 439
U1 1
U2 4
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD SEP 27
PY 2001
VL 345
IS 13
BP 948
EP 955
DI 10.1056/NEJMoa010845
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 475NF
UT WOS:000171170000003
PM 11575286
ER

PT J
AU Rahman, MU
   Fan, CM
   Choi, HK
   McCluskey, RT
   Niles, J
AF Rahman, MU
   Fan, CM
   Choi, HK
   McCluskey, RT
   Niles, J
TI A 22-year-old man with hyperthyroidism, fever, abdominal pain, and
   arthralgia. Vasculitis associated with antineutrophil cytoplasmic
   antibodies.
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID POSITIVE CRESCENTIC GLOMERULONEPHRITIS; MICROSCOPIC POLYARTERITIS;
   GRAVES-DISEASE; PROPYLTHIOURACIL; ANCA; CLASSIFICATION; PREVALENCE;
   THERAPY; NODOSA
C1 Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Rahman, MU (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA.
NR 24
TC 2
Z9 2
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD SEP 27
PY 2001
VL 345
IS 13
BP 981
EP 986
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 475NF
UT WOS:000171170000008
ER

PT J
AU Mullan, PB
   Quinn, JE
   Gilmore, PM
   McWilliams, S
   Andrews, H
   Gervin, C
   McCabe, N
   McKenna, S
   White, P
   Song, YH
   Maheswaran, S
   Liu, E
   Haber, DA
   Johnston, PG
   Harkin, DP
AF Mullan, PB
   Quinn, JE
   Gilmore, PM
   McWilliams, S
   Andrews, H
   Gervin, C
   McCabe, N
   McKenna, S
   White, P
   Song, YH
   Maheswaran, S
   Liu, E
   Haber, DA
   Johnston, PG
   Harkin, DP
TI BRCA1 and GADD45 mediated G2/M cell cycle arrest in response to
   antimicrotubule agents
SO ONCOGENE
LA English
DT Article
DE BRCA1; GADD45; antimicrotubule agents; G2/M arrest; cell death
ID DNA-DAMAGE RESPONSE; TRANSCRIPTION-COUPLED REPAIR; POLYMERASE-II
   HOLOENZYME; GENE-EXPRESSION; PROTEIN; PHOSPHORYLATION; ASSOCIATION;
   ACTIVATION; CHECKPOINT; INDUCTION
AB BRCA1 is a tumour suppressor gene implicated in the predisposition to early onset breast and ovarian cancer. We have generated cell lines with inducible expression of BRCA1 to evaluate its role in mediating the cellular response to various chemotherapeutic drugs commonly used in the treatment of breast and ovarian cancer. Induction of BRCA1 in the presence of Taxol and Vincristine resulted in a dramatic increase in cell death; an effect that was preceded by an acute arrest at the G2/M phase of the cell cycle and which correlated with BRCA1 mediated induction of GADD45. A proportion of the arrested cells were blocked in mitosis suggesting activation of both a G2 and a mitotic spindle checkpoint. In contrast, no specific interaction was observed between BRCA1 induction and treatment of cells with a range of DNA damaging agents including Cisplatin and Adriamycin. Inducible expression of GADD45 in the presence of Taxol induced both G2 and mitotic arrest in these cells consistent with a role for GADD45 in contributing to these effects. Our results support a role for both BRCA1 and GADD45 in selectively regulating a G2/M checkpoint in response to antimicrotubule agents and raise the possibility that their expression levels in cells may contribute to the toxicity observed with these compounds.
C1 Queens Univ Belfast, Canc Res Ctr, Dept Oncol, Belfast BT9 7AB, Antrim, North Ireland.
   Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Charlestown, MA 02129 USA.
   Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA.
   NIH, Div Clin Sci, Bethesda, MD 20892 USA.
RP Harkin, DP (reprint author), Queens Univ Belfast, Belfast City Hosp, Canc Res Ctr, Dept Oncol, Univ Floor,Lisburn Rd, Belfast BT9 7AB, Antrim, North Ireland.
RI Liu, Edison/C-4141-2008
NR 40
TC 116
Z9 120
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 SEP 27
PY 2001
VL 20
IS 43
BP 6123
EP 6131
DI 10.1038/sj.onc.1204712
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 476BL
UT WOS:000171206300003
PM 11593420
ER

PT J
AU Alevizos, I
   Mahadevappa, M
   Zhang, X
   Ohyama, H
   Kohno, Y
   Posner, M
   Gallagher, GT
   Varvares, M
   Cohen, D
   Kim, D
   Kent, R
   Donoff, RB
   Todd, R
   Yung, CM
   Warrington, JA
   Wong, DTW
AF Alevizos, I
   Mahadevappa, M
   Zhang, X
   Ohyama, H
   Kohno, Y
   Posner, M
   Gallagher, GT
   Varvares, M
   Cohen, D
   Kim, D
   Kent, R
   Donoff, RB
   Todd, R
   Yung, CM
   Warrington, JA
   Wong, DTW
TI Oral cancer in vivo gene expression profiling assisted by laser capture
   microdissection and microarray analysis
SO ONCOGENE
LA English
DT Article
DE oral cancer; gene expression; laser capture microdissection; microarrays
ID SQUAMOUS-CELL CARCINOMA; NEUROMEDIN-U; PROGNOSTIC-SIGNIFICANCE;
   OLIGONUCLEOTIDE ARRAYS; METABOLIZING-ENZYMES; CATHEPSIN-L; HUMAN HEAD;
   NECK; IDENTIFICATION; DIFFERENTIATION
AB Large scale gene expression profiling was carried out on laser capture microdissected (LCM) tumor and normal oral epithelial cells and analysed on high-density oligonucleotide microarrays. About 600 genes were found to be oral cancer associated. These oral cancer associated genes include oncogenes, tumor suppressors, transcription factors, xenobiotic enzymes, metastatic proteins, differentiation markers, and genes that have not been implicated in oral cancer. The database created provides a verifiable global profile of gene expression during oral carcinogenesis, revealing the potential role of known genes as well as genes that have not been previously implicated in oral cancer.
C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Biol, Boston, MA 02115 USA.
   Affymetrix Inc, Santa Clara, CA 95051 USA.
   China Med Univ, Dept Biol, Shenyang 110001, Peoples R China.
   Dana Farber Canc Inst, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA.
   Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02115 USA.
   Univ Nebraska, Coll Dent, Ctr Med, Lincoln, NE 68583 USA.
   Forsyth Inst, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
   Chung Shan Med & Dent Coll, Taichung, Taiwan.
RP Wong, DTW (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Biol, 188 Longwood Ave, Boston, MA 02115 USA.
FU NIDCR NIH HHS [P01 DE12467, P30 DE11814, R29 DE11983]
NR 47
TC 150
Z9 164
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD SEP 27
PY 2001
VL 20
IS 43
BP 6196
EP 6204
DI 10.1038/sj.onc.1204685
PG 9
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 476BL
UT WOS:000171206300011
PM 11593428
ER

PT J
AU Baid, S
   Cosimi, AB
   Farrell, ML
   Schoenfeld, DA
   Feng, S
   Chung, RT
   Tolkoff-Rubin, N
   Pascual, M
AF Baid, S
   Cosimi, AB
   Farrell, ML
   Schoenfeld, DA
   Feng, S
   Chung, RT
   Tolkoff-Rubin, N
   Pascual, M
TI Posttransplant diabetes mellitus in liver transplant recipients: Risk
   factors, temporal relationship with hepatitis C virus allograft
   hepatitis, and impact on mortality
SO TRANSPLANTATION
LA English
DT Article
ID INFECTION; PREVALENCE; ASSOCIATION; DISEASE; HCV; CIRRHOSIS; RNA
AB Background. Recent studies suggest an association between diabetes mellitus and hepatitis C virus (HCV) infection. Our aim was to determine (1) the prevalence and determinants of new onset posttransplant diabetes mellitus (PTDM) in HCV (+) liver transplant (OLT) recipients, (2) the temporal relationship between recurrent allograft hepatitis and the onset of PTDM, and (3) the effects of antiviral therapy on glycemic control.
   Methods. Between January of 1991 and December of 1998, of 185 OLTs performed in 176 adult patients, 47 HCV (+) cases and 111 HCV (-) controls were analyzed. We reviewed and analyzed the demographics, etiology of liver failure, pretransplant alcohol abuse, prevalence of diabetes mellitus, and clinical characteristics of both groups. In HCV (+) patients, the development of recurrent allograft hepatitis and its therapy were also studied in detail.
   Results. The prevalence of pretransplant diabetes was similar in the two groups, whereas the prevalence of PTDM was significantly higher in HCV (+) than in HCV (-) patients (64% vs. 28%, P=0.0001). By multivariate analysis, HCV infection (hazard ratio 2.5, P=0.001) and methylprednisolone boluses (hazard ratio 1.09 per bolus,, P=0.02) were found to be independent risk factors for the development of PTDM. Development of PTDM was found to be an independent risk factor for mortality (hazard ratio 3.67, P <0.0001). The cumulative mortality in HCV (+) PTDM (+) versus HCV (+) PTDM (-) patients was 56% vs. 14% (P=0.001). In HCV (+) patients with PTDM, we could identify two groups based on the temporal relationship between the allograft hepatitis and the onset of PTDM: 13 patients developed PTDM either before or in the absence of hepatitis (group A), and 12 concurrently with the diagnosis of hepatitis (group B). In gr. B, 11 of 12 patients received antiviral therapy. Normalization of liver function tests with improvement in viremia was achieved in 4 of 11 patients, who also demonstrated a marked improvement in their glycemic control.
   Conclusion. We found a high prevalence of PTDM in HCV (+) recipients. PTDM after OLT was associated with significantly increased mortality. HCV infection and methylprednisolone boluses were found to be independent risk factors for the development of PTDM. In approximately half of the HCV (+) patients with PTDM, the onset of PTDM was related to the recurrence of allograft hepatitis. Improvement in glycemic control was achieved in the patients who responded to antiviral therapy.
C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Baid, S (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA.
FU NIDDK NIH HHS [R01DK57857]
NR 34
TC 165
Z9 172
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0041-1337
J9 TRANSPLANTATION
JI Transplantation
PD SEP 27
PY 2001
VL 72
IS 6
BP 1066
EP 1072
DI 10.1097/00007890-200109270-00015
PG 7
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 476QD
UT WOS:000171239500015
PM 11579302
ER

PT J
AU Shekelle, PG
   Ortiz, E
   Rhodes, S
   Morton, SC
   Eccles, MP
   Grimshaw, JM
   Woolf, SH
AF Shekelle, PG
   Ortiz, E
   Rhodes, S
   Morton, SC
   Eccles, MP
   Grimshaw, JM
   Woolf, SH
TI Validity of the agency for healthcare research and quality clinical
   practice guidelines - How quickly do guidelines become outdated?
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
AB Context Practice guidelines need to be up-to-date to be useful to clinicians. No published methods are available for assessing whether existing practice guidelines are still valid, nor does any empirical information exist regarding how often such assessments need to be made.
   Objectives To assess the current validity of 17 clinical practice guidelines published by the US Agency for Healthcare Research and Quality (AHRQ) that are still in circulation, and to use this information to estimate how quickly guidelines become obsolete.
   Design, Setting, and Participants We developed criteria for defining when a guideline needs updating, mailed surveys to members of the original AHRQ guideline panels (n = 170; response rate, 71%), and searched the literature for evidence through March 2000 (n = 6994 titles yielding 173 articles plus 159 new guidelines on the same topics).
   Main Outcome Measures Identification of new evidence calling for a major, minor, or no update of the 17 guidelines; survival analysis of the rate at which guidelines became outdated.
   Results For 7 guidelines, new evidence and expert judgment indicated that a major update is required; 6 were found to be in need of a minor update; 3 were judged as still valid; and for 1 guideline, we could reach no conclusion. Survival analysis indicated that about half the guidelines were outdated in 5.8 years (95% confidence interval [CI], 5.0-6.6 years). The point at which no more than 90% of the guidelines were still valid was 3.6 years (95% CI, 2.6-4.6 years).
   Conclusions More than three quarters of the AHRQ guidelines need updating. As a general rule, guidelines should be reassessed for validity every 3 years.
C1 RAND Corp, Hlth Div, So Calif Evidence Based Pratice Ctr, Santa Monica, CA 90401 USA.
   Greater Los Angeles Vet Affairs Hlth Care Syst, Los Angeles, CA USA.
   Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
   San Diego Vet Affairs Hlth Care Syst, San Diego, CA USA.
   Univ Newcastle Upon Tyne, Ctr Hlth Serv Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
   Univ Aberdeen, Hlth Serv Res Unit, Aberdeen, Scotland.
   Virginia Commonwealth Univ, Dept Family Practice, Richmond, VA USA.
RP Shekelle, PG (reprint author), RAND Corp, Hlth Div, So Calif Evidence Based Pratice Ctr, 1700 Main St,POB 2138, Santa Monica, CA 90401 USA.
RI Grimshaw, Jeremy/D-8726-2013; 
OI Grimshaw, Jeremy/0000-0001-8015-8243
FU PHS HHS [290-97-0001]
NR 6
TC 268
Z9 282
U1 1
U2 7
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 SEP 26
PY 2001
VL 286
IS 12
BP 1461
EP 1467
DI 10.1001/jama.286.12.1461
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 475UX
UT WOS:000171188600023
PM 11572738
ER

PT J
AU Rosas, HD
   Goodman, J
   Chen, YI
   Jenkins, BG
   Kennedy, DN
   Makris, N
   Patti, M
   Seidman, LJ
   Beal, MF
   Koroshetz, WJ
AF Rosas, HD
   Goodman, J
   Chen, YI
   Jenkins, BG
   Kennedy, DN
   Makris, N
   Patti, M
   Seidman, LJ
   Beal, MF
   Koroshetz, WJ
TI Striatal volume loss in HD as measured by MRI and the influence of CAG
   repeat
SO NEUROLOGY
LA English
DT Article
ID BASAL GANGLIA VOLUME; MAGNETIC-RESONANCE IMAGES; HUNTINGTONS-DISEASE;
   MORPHOMETRIC ANALYSIS; TOURETTES-SYNDROME; HUMAN BRAIN; AGE
AB Background: Hunting-ton's disease (HD) is an autosomal dominant neurodegenerative disease that results from the expansion of a trinucleotide (CAG) repeat on chromosome 4. Progressive degeneration of the striatum is the pathologic hallmark of the disease. Little is known about the regional selectivity of the neurodegeneration and its relationship to the genetic expansion. Methods: The authors used high-resolution MRI to determine the relationship between the genetic expansion and the degree of striatal degeneration. Morphometric analyses of the striatum from high-resolution MR images from 27 subjects with HD were compared with those of 24 healthy control subjects. Results and conclusions: Striatal volumes were reduced in subjects with HD as compared with control subjects, in agreement with previously published reports. Left-sided volumes were smaller than right-sided volumes in subjects with HD; in healthy subjects, right-sided volumes were smaller. Finally, volume loss was significantly correlated with CAG repeat number. These results have potential implications for the design and assessment of therapeutic agents in the future.
C1 Massachusetts Gen Hosp, Neurol Serv, Dept Neurol, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA USA.
   Harvard Univ, Sch Med, Charlestown, MA USA.
RP Rosas, HD (reprint author), Massachusetts Gen Hosp, Neurol Serv, Dept Neurol, Warren 408,82 Fruit St, Boston, MA 02114 USA.
RI Kennedy, David/H-3627-2012
FU NIMH NIH HHS [MH00976, MH43518, MH56956]
NR 25
TC 80
Z9 81
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD SEP 25
PY 2001
VL 57
IS 6
BP 1025
EP 1028
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 474PK
UT WOS:000171115900017
PM 11571328
ER

PT J
AU DeStefano, AL
   Golbe, LI
   Mark, MH
   Lazzarini, AM
   Maher, NE
   Saint-Hilaire, M
   Feldman, RG
   Guttman, M
   Watts, RL
   Suchowersky, O
   Lafontaine, AL
   Labelle, N
   Lew, MF
   Waters, CH
   Growdon, JH
   Singer, C
   Currie, LJ
   Wooten, GF
   Vieregge, P
   Pramstaller, PP
   Klein, C
   Hubble, JP
   Stacy, M
   Montgomery, E
   MacDonald, ME
   Gusella, JF
   Myers, RH
AF DeStefano, AL
   Golbe, LI
   Mark, MH
   Lazzarini, AM
   Maher, NE
   Saint-Hilaire, M
   Feldman, RG
   Guttman, M
   Watts, RL
   Suchowersky, O
   Lafontaine, AL
   Labelle, N
   Lew, MF
   Waters, CH
   Growdon, JH
   Singer, C
   Currie, LJ
   Wooten, GF
   Vieregge, P
   Pramstaller, PP
   Klein, C
   Hubble, JP
   Stacy, M
   Montgomery, E
   MacDonald, ME
   Gusella, JF
   Myers, RH
TI Genome-wide scan for Parkinson's disease: The GenePD study
SO NEUROLOGY
LA English
DT Article
ID POLYMORPHISM; LOCUS
AB A genome-wide scan for idiopathic PD in a sample of 113 PD-affected sibling pairs is reported. Suggestive evidence for linkage was found for chromosomes 1 (214 cM, lod = 1.20), 9 (136 cM, lod = 1.30), 10 (88 cM, lod = 1.07), and 16 (114 cM, lod = 0.93). The chromosome 9 region overlaps the genes for dopamine P-hydroxylase and torsion dystonia. Although no strong evidence for linkage was found for any locus, these results may be of value in comparison with similar studies by others.
C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
   Boston Univ, Sch Med, Dept Epidemiol & Biostat, Boston, MA 02118 USA.
   Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA.
   Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA 02118 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
   Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA.
   Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA.
   Univ So Calif, Dept Neurol, Los Angeles, CA USA.
   Univ Miami, Dept Neurol, Coral Gables, FL 33124 USA.
   Univ Virginia, Hlth Syst, Dept Neurol, Charlottesville, VA USA.
   Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA.
   Barrow Clin, Dept Neurol, Phoenix, AZ USA.
   Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA.
   Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA.
   Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany.
   Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada.
   Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada.
   Univ Calgary, Dept Med Genet, Calgary, AB T2N 1N4, Canada.
RP Myers, RH (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B-603, Boston, MA 02118 USA.
RI Pramstaller, Peter/C-2357-2008
FU NINDS NIH HHS [R0-1 NS36711-01]
NR 10
TC 58
Z9 58
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 SEP 25
PY 2001
VL 57
IS 6
BP 1124
EP 1126
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA 474PK
UT WOS:000171115900040
PM 11571351
ER

PT J
AU Takagi, J
   Beglova, N
   Yalamanchili, P
   Blacklow, SC
   Springer, TA
AF Takagi, J
   Beglova, N
   Yalamanchili, P
   Blacklow, SC
   Springer, TA
TI Definition of EGF-like, closely interacting modules that bear activation
   epitopes in integrin beta subunits
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID LIGAND-BINDING SITE; CR3-DEPENDENT ADHESION; CONFORMATIONAL-CHANGES;
   GENOMIC ORGANIZATION; MONOCLONAL-ANTIBODY; I-DOMAIN; PROTEINS;
   GLYCOPROTEIN; HOMOLOGY; CLONING
AB Integrin beta subunits contain four cysteine-rich repeats in a long extracellular stalk that connects the headpiece to the membrane. Most mAbs to integrin activation epitopes map to these repeats, and they are important in propagating conformational signals from the membrane/cytosol to the ligand-binding headpiece. Sequence analysis of a protein containing only 10 integrin-like, cysteine-rich repeats suggests that these repeats start one cysteine earlier than previously reported. By using the new repeat boundaries, statistically significant sequence homology to epidermal growth factor-like domains is found, and a disulfide bond connectivity of the eight cysteines is predicted that differs in three of four disulfides from a previous prediction of epidermal growth factor-like modules [Berg, R. W., Leung, E., Gough, S., Morris, C., Yao, W.-P., Wang, S.-x., Ni, J. & Krissansen, G. W. (1999) Genomics 56, 169-178]. N-terminally truncated beta2 integrin stalk fragments were well expressed and secreted from 293 T cells when they began at repeat boundaries but not when they began one cysteine earlier or later. Furthermore, peptides that correspond to module 3 or modules 2 + 3 were expressed in bacteria and refolded. The module 2 + 3 fragment was as reactive with three mAbs to activation epitopes as a beta2 fragment expressed in eukaryotic cells, indicating a native fold. Only one residue intervenes between the last cysteine of one module and the first cysteine of the next. This arrangement is consistent with a tight intermodule connection, a prerequisite for signal propagation from the membrane to the ligand binding headpiece.
C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Brigham & Womens Hosp, 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, 200 Longwood Ave, Boston, MA 02115 USA.
FU NCI NIH HHS [CA31798, R01 CA031798, R37 CA031798]; NHLBI NIH HHS
   [HL54936, HL61001, R01 HL054936, R01 HL061001]
NR 45
TC 37
Z9 38
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 SEP 25
PY 2001
VL 98
IS 20
BP 11175
EP 11180
DI 10.1073/pnas.201420198
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PC
UT WOS:000171237100038
PM 11572973
ER

PT J
AU Geng, LP
   Pfister, S
   Kraeft, SK
   Rudd, CE
AF Geng, LP
   Pfister, S
   Kraeft, SK
   Rudd, CE
TI Adaptor FYB (Fyn-binding protein) regulates integrinmediated adhesion
   and mediator release: Differential involvement of the FYBSH3 domain
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID AFFINITY IGE RECEPTOR; FC-EPSILON-RI; BASOPHILIC LEUKEMIA-CELLS;
   TYROSINE PHOSPHORYLATION; MAST-CELLS; T-CELLS; SIGNAL TRANSDUCTION;
   MOLECULAR-CLONING; RBL-2H3 CELLS; KINASE
AB Aggregation of the high-affinity IgE receptor (Fc epsilon RI) on mast cells activates a tyrosine phosphorylation cascade that is required for adhesion and degranulation events leading to the release of histamine and other inflammatory mediators. The full range of intracellular mediators that regulate this process is unknown. Recent studies have identified a group of immune cell-specific adaptor proteins that include linker for activation of T-cell (LAT), SH2-domain-containing leukocyte protein (SLP-76), and Fyn-T-binding protein (FYB)/SLP-76-associated protein (SLAP). In this study, we demonstrate that FYB can up-regulate integrin-mediated adhesion to fibronectin and mediator release in RBL-2H3 mast cells. The regulation of these two events could be distinguished from each other by the requirement of the FYB SH3 domain in beta -hexosaminidase release, but not adhesion, and the up-regulation of mediator release by FYB in nonadherent cells. Fc epsilon RI aggregation increased FYB tyrosine phosphorylation, whereas confocal immunofluorescence microscopy showed that FYB colocalizes with Factin in membrane ruffles and plaques. our findings identify FYB as a regulator of integrin-mediated adhesion and degranulation events, which, in the case of mast cells, has potential applications to inflammatory and allergic responses.
C1 Harvard Univ, Sch Med, Div Tumor Immunol, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Haematol, Sch Med, London W12 0NN, England.
RP Rudd, CE (reprint author), Harvard Univ, Sch Med, Div Tumor Immunol, Dept Canc Immunol & AIDS,Dana Farber Canc Inst, Boston, MA 02115 USA.
RI Wan, Daniel/F-4689-2010; Pfister, Stefan/F-6860-2013
OI Pfister, Stefan/0000-0002-5447-5322
FU NIAID NIH HHS [AI39021]
NR 46
TC 59
Z9 60
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 SEP 25
PY 2001
VL 98
IS 20
BP 11527
EP 11532
DI 10.1073/pnas.191378198
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PC
UT WOS:000171237100098
PM 11553777
ER

PT J
AU Kwabi-Addo, B
   Giri, D
   Schmidt, K
   Podsypanina, K
   Parsons, R
   Greenberg, N
   Ittmann, M
AF Kwabi-Addo, B
   Giri, D
   Schmidt, K
   Podsypanina, K
   Parsons, R
   Greenberg, N
   Ittmann, M
TI Haploinsufficiency of the Pten tumor suppressor gene promotes prostate
   cancer progression
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID FREQUENT INACTIVATION; PTEN/MMAC1 GENE; COWDEN-DISEASE; CELL-LINES;
   BREAST; 10Q23; EXPRESSION; MICE; ADENOCARCINOMAS; ANGIOGENESIS
AB The PTEN gene encodes a lipid phosphatase that negatively regulates the phosphatidylinositol 3-kinase pathway and is inactivated in a wide variety of malignant neoplasms. High rates of loss of heterozygosity are observed at the 10q23.3 region containing the human PTEN gene in prostate cancer and other human malignancies, but the demonstrated rate of biallelic inactivation of the PTEN gene by mutation or homozygous deletion is significantly lower than the rate of loss of heterozygosity. The transgenic adenocarcinoma of mouse prostate model is a well characterized animal model of prostate cancer. Analysis of prostate cancer progression in transgenic adenocarcinoma of mouse prostate mice bred to Pten(+/-) heterozygous mice, coupled with analysis of the Pten gene and protein in the resulting tumors, reveals that haploinsufficiency of the Pten gene promotes the progression of prostate cancer in this model system. This observation provides a potential explanation for the discordance in rates of loss of heterozygosity at 10q23 and biallelic PTEN inactivation observed in prostate cancer and many human malignancies.
C1 Houston VAMC, Res Serv, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA.
   Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA.
   Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA.
RP Ittmann, M (reprint author), Houston VAMC, Res Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA.
RI Kwabi-Addo, Bernard/A-6993-2016
OI Kwabi-Addo, Bernard/0000-0003-3692-6350
NR 33
TC 208
Z9 211
U1 1
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 25
PY 2001
VL 98
IS 20
BP 11563
EP 11568
DI 10.1073/pnas.201167798
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PC
UT WOS:000171237100104
PM 11553783
ER

PT J
AU Namura, S
   Iihara, K
   Takami, S
   Nagata, I
   Kikuchi, H
   Matsushita, K
   Moskowitz, MA
   Bonventre, JV
   Alessandrini, A
AF Namura, S
   Iihara, K
   Takami, S
   Nagata, I
   Kikuchi, H
   Matsushita, K
   Moskowitz, MA
   Bonventre, JV
   Alessandrini, A
TI Intravenous administration of MEK inhibitor U0126 affords brain
   protection against forebrain ischemia and focal cerebral ischemia
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; CULTURED CORTICAL-NEURONS; SIGNAL-REGULATED
   KINASE; TYROSINE PHOSPHORYLATION; NITRIC-OXIDE; CELL-LINE; DIFFERENTIAL
   ACTIVATION; INJURY; RECEPTOR; DEATH
AB Brain subjected to acute ischemic attack caused by an arterial blockage needs immediate arterial recanalization. However, restoration of cerebral blood flow can cause tissue injury, which is termed reperfusion injury. It is important to inhibit reperfusion injury to achieve greater brain protection. Because oxidative stress has been shown to activate mitogen-activated protein kinases (MAPKs), and because oxidative stress contributes to reperfusion injury, MAPK may be a potential target to inhibit reperfusion injury after brain ischemia. Here, we demonstrate that reperfusion after forebrain ischemia dramatically increases phosphorylation level of extracellular signal-regulated kinase 2 (ERK2) in the gerbil hippocampus. In addition, i.v. administration of U0126 (100-200 mg/kg), a specific inhibitor of MEK (MAPK/ERK kinase), protects the hippocampus against forebrain ischemia. Moreover, treatment with U0126 at 3 h after ischemia significantly reduces infarct volume after transient (3 h) focal cerebral ischemia in mice. This protection is accompanied by reduced phosphorylation level of ERK2, substrates for MEK, in the damaged brain areas. Furthermore, U0126 protects mouse primary cultured cortical neurons against oxygen deprivation for 9 h as well as nitric oxide toxicity. These results provide further evidence for the role of MEK/ERK activation in brain injury resulting from ischemia/reperfusion, and indicate that MEK inhibition may increase the resistance of tissue to ischemic injury.
C1 Natl Cardiovasc Ctr, Res Inst, Suita, Osaka 5658565, Japan.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA.
RP Namura, S (reprint author), Natl Cardiovasc Ctr, Res Inst, 5-7-1 Fujishirodai, Suita, Osaka 5658565, Japan.
RI Moskowitz, Michael/D-9916-2011
NR 37
TC 276
Z9 300
U1 0
U2 6
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 SEP 25
PY 2001
VL 98
IS 20
BP 11569
EP 11574
DI 10.1073/pnas.181213498
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PC
UT WOS:000171237100105
PM 11504919
ER

PT J
AU Vaina, LM
   Solomon, J
   Chowdhury, S
   Sinha, P
   Belliveau, JW
AF Vaina, LM
   Solomon, J
   Chowdhury, S
   Sinha, P
   Belliveau, JW
TI Functional neuroanatomy of biological motion perception in humans
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID HUMAN VISUAL-CORTEX; INFERIOR TEMPORAL CORTEX; FUSIFORM FACE AREA; HUMAN
   BRAIN; INFEROTEMPORAL CORTEX; RESPONSIVE REGIONS; POLYSENSORY AREA;
   MACAQUE MONKEY; CORTICAL AREAS; FROM-MOTION
AB We used whole brain functional MRI to investigate the neural network specifically engaged in the recognition of "biological motion" defined by point-lights attached to the major joints and head of a human walker. To examine the specificity of brain regions responsive to biological motion, brain activations obtained during a "walker vs. non-walker" discrimination task were compared with those elicited by two other tasks: (i) non-rigid motion (NRM), involving the discrimination of overall motion direction in the same "point-lights" display, and (ii) face-gender discrimination, involving the discrimination of gender in briefly presented photographs of men and women. Brain activity specific to "biological motion" recognition arose in the lateral cerebellum and in a region in the lateral occipital cortex presumably corresponding to the area KO previously shown to be particularly sensitive to kinetic contours. Additional areas significantly activated during the biological motion recognition task involved both, dorsal and ventral extrastriate cortical regions. In the ventral regions both face-gender discrimination and biological motion recognition elicited activation in the lingual and fusiform gyri and in the Brodmann areas 22 and 38 in superior temporal sulcus (STS). Along the dorsal pathway, both biological motion recognition and non-rigid direction discrimination gave rise to strong responses in several known motion sensitive areas. These included Brodmann areas 19/37, the inferior (Brodmann Area 39), and superior parietal lobule (Brodmann Area 7). Thus, we conjecture that, whereas face (and form) stimuli activate primarily the ventral system and motion stimuli primarily the dorsal system, recognition of biological motion stimuli may activate both systems as well as their confluence in STS. This hypothesis is consistent with our findings in stroke patients, with unilateral brain lesions involving at least one of these areas, who, although correctly reporting the direction of the point-light walker, fail on the biological motion task.
C1 Boston Univ, Brain & Vis Res Lab, Dept Biomed Engn & Neurol, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA.
   MIT, Dept Cognit Sci, Cambridge, MA 02215 USA.
   Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02129 USA.
   Sensor Syst Inc, Sterling, VA 20164 USA.
RP Vaina, LM (reprint author), Boston Univ, Brain & Vis Res Lab, Dept Biomed Engn & Neurol, 44 Cummington St, Boston, MA 02215 USA.
FU NCRR NIH HHS [P41 RR014075, P41-RR14075]; NEI NIH HHS [EY2-RO1-07861,
   R01 EY007861]; NINDS NIH HHS [R01 NS037462, R01 NS37462]
NR 54
TC 299
Z9 303
U1 1
U2 16
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 SEP 25
PY 2001
VL 98
IS 20
BP 11656
EP 11661
DI 10.1073/pnas.191374198
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PC
UT WOS:000171237100120
PM 11553776
ER

PT J
AU Tuch, DS
   Wedeen, VJ
   Dale, AM
   George, JS
   Belliveau, JW
AF Tuch, DS
   Wedeen, VJ
   Dale, AM
   George, JS
   Belliveau, JW
TI Conductivity tensor mapping of the human brain using diffusion tensor
   MRI
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID ELECTRICAL-CONDUCTIVITY; MAGNETIC-RESONANCE; FINITE-ELEMENT; TISSUE;
   MODEL; ANISOTROPY; FIELDS; FLUID; MEDIA; ROCKS
AB Knowledge of the electrical conductivity properties of excitable tissues is essential for relating the electromagnetic fields generated by the tissue to the underlying electrophysiological currents. Efforts to characterize these endogenous currents from measurements of the associated electromagnetic fields would significantly benefit from the ability to measure the electrical conductivity properties of the tissue noninvasively. Here, using an effective medium approach, we show how the electrical conductivity tensor of tissue can be quantitatively inferred from the water selfdiffusion tensor as measured by diffusion tensor magnetic resonance imaging. The effective medium model indicates a strong linear relationship between the conductivity and diffusion tensor eigenvalues (respectively, sigma and d) in agreement with theoretical bounds and experimental measurements presented here (sigma /d approximate to 0.844 +/- 0.0545 S.s/mm(3), r(2) = 0.945). The extension to other biological transport phenomena is also discussed.
C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA.
   MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   MIT, Dept Nucl Engn, Cambridge, MA 02139 USA.
   Los Alamos Natl Lab, Biophys Grp, Los Alamos, NM 87545 USA.
RP Tuch, DS (reprint author), Massachusetts Gen Hosp, NMR Ctr, 149 13th St, Charlestown, MA 02129 USA.
RI Dale, Anders/A-5180-2010
FU NIMH NIH HHS [MH 60993-04]
NR 37
TC 198
Z9 206
U1 3
U2 18
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 25
PY 2001
VL 98
IS 20
BP 11697
EP 11701
DI 10.1073/pnas.171473898
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PC
UT WOS:000171237100127
PM 11573005
ER

PT J
AU Blood, AJ
   Zatorre, RJ
AF Blood, AJ
   Zatorre, RJ
TI Intensely pleasurable responses to music correlate with activity in
   brain regions implicated in reward and emotion
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID NUCLEUS-ACCUMBENS DOPAMINE; FRONTAL-LOBE DAMAGE; HUMAN AMYGDALA;
   MECHANISMS; PERCEPTION; COCAINE; PITCH; RATS; TRANSMISSION; ACTIVATION
AB We used positron emission tomography to study neural mechanisms underlying intensely pleasant emotional responses to music. Cerebral blood flow changes were measured in response to subject-selected music that elicited the highly pleasurable experience of "shivers-down-the-spine" or "chills." Subjective reports of chills were accompanied by changes in heart rate, electromyogram, and respiration. As intensity of these chills increased, cerebral blood flow increases and decreases were observed in brain regions thought to be involved in reward/motivation, emotion, and arousal, including ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex. These brain structures are known to be active in response to other euphoria-inducing stimuli, such as food, sex, and drugs of abuse. This finding links music with biologically relevant, survival-related stimuli via their common recruitment of brain circuitry involved in pleasure and reward.
C1 McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada.
RP Blood, AJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, CNY 149-2301,13th St, Charlestown, MA 02129 USA.
NR 40
TC 859
Z9 886
U1 41
U2 219
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 SEP 25
PY 2001
VL 98
IS 20
BP 11818
EP 11823
DI 10.1073/pnas.191355898
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 476PC
UT WOS:000171237100148
PM 11573015
ER

PT J
AU Dedier, J
   Singer, DE
   Chang, YC
   Moore, M
   Atlas, SJ
AF Dedier, J
   Singer, DE
   Chang, YC
   Moore, M
   Atlas, SJ
TI Processes of care, illness severity, and outcomes in the management of
   community-acquired pneumonia at academic hospitals
SO ARCHIVES OF INTERNAL MEDICINE
LA English
DT Article; Proceedings Paper
CT 23rd Annual Meeting of the Society-for-General-Internal Medicine
CY MAY 04-06, 2000
CL BOSTON, MASSACHUSETTS
SP Soc Gen Internal Med
ID QUALITY; GUIDELINES
AB Background: Prompt antibiotic administration, oxygenation measurement, and blood cultures are generally considered markers of high-quality care in the inpatient management of community-acquired pneumonia (CAP). However, few studies have examined the relationship between prompt achievement of process-of-care markers and outcomes for patients with CAP. We examined whether antibiotic administration within 8 hours of hospital arrival, a blood culture within 24 hours, an oxygenation measurement within 24 hours, or performing blood cultures before giving antibiotics was associated with the following: (1) reaching clinical stability within 48 hours of hospital admission, (2) a decreased length of hospital stay, or (3) fewer inpatient deaths.
   Methods: A retrospective medical record review identified 1062 eligible patients discharged from the hospital with a diagnosis of CAP between December 1, 1997, and February 28, 1998, among 38 US academic hospitals. We assessed the independent relationship between each process marker and the 3 clinical outcomes, controlling for the Pneumonia Severity Index on admission. We also examined the relationship of pneumonia severity on admission to process marker achievement and clinical outcomes.
   Results: Overall, there was no consistent or statistically significant relationship between achieving process markers and better clinical outcomes (P > .40 for all). We did observe that performing blood cultures within 24 hours was related to not achieving clinical stability within 48 hours (odds ratio, 1.62; 95% confidence interval, 1.13-2.33). However, this finding likely reflects residual confounding by severity of illness, since increasing pneumonia seventy on admission was associated with blood culture performance (P=.009) and with shorter times to antibiotic administration (P=.04).
   Conclusions: Achieving process-of-care markers was not associated with improved outcomes, but was related to the severity of pneumonia as assessed on admission. Our results highlight the difficulty in demonstrating a link between process-of-care markers and outcomes in observational studies of CAP. Randomized studies are needed to objectively evaluate the impact of process-of-care markers on CAP outcomes.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gen Med Div,Clin Epidemiol Unit, Boston, MA USA.
   Univ Healthsyst Consortium, Oak Brook, IL USA.
RP Dedier, J (reprint author), Boston Med Ctr, Sect Gen Internal Med Res Unit, Dept Med, 91 E Concord St,Suite 200, Boston, MA 02118 USA.
NR 20
TC 72
Z9 72
U1 0
U2 0
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 SEP 24
PY 2001
VL 161
IS 17
BP 2099
EP 2104
DI 10.1001/archinte.161.17.2099
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 473QJ
UT WOS:000171056600004
PM 11570938
ER

PT J
AU Carding, P
   Hillman, R
AF Carding, P
   Hillman, R
TI More randomised controlled studies in speech and language therapy -
   Complex behavioural interventions can be evaluated
SO BRITISH MEDICAL JOURNAL
LA English
DT Editorial Material
ID CONTROLLED TRIALS; HEALTH
C1 Univ Newcastle Upon Tyne, Freeman Hosp, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England.
   Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Carding, P (reprint author), Univ Newcastle Upon Tyne, Freeman Hosp, Newcastle Upon Tyne NE7 7DN, Tyne & Wear, England.
NR 12
TC 8
Z9 8
U1 2
U2 2
PU BRITISH MED JOURNAL PUBL GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0959-535X
J9 BRIT MED J
JI Br. Med. J.
PD SEP 22
PY 2001
VL 323
IS 7314
BP 645
EP 646
DI 10.1136/bmj.323.7314.645
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA 476LP
UT WOS:000171228800003
PM 11566815
ER

PT J
AU Li, YQ
   Ren, J
   Yu, WH
   Li, Q
   Kuwahara, H
   Yin, L
   Carraway, KL
   Kufe, D
AF Li, YQ
   Ren, J
   Yu, WH
   Li, Q
   Kuwahara, H
   Yin, L
   Carraway, KL
   Kufe, D
TI The epidermal growth factor receptor regulates interaction of the human
   DF3/MUC1 carcinoma antigen with c-Src and beta-catenin
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID TYROSINE KINASES; ASSOCIATION; PROTEIN; TRANSFORMATION; CELLS; GRB2; DF3
AB The DF3/MUC1 mucin-like, transmembrane glycoprotein is aberrantly overexpressed in most human carcinomas. The MUC1 cytoplasmic domain interacts with the c-Src tyrosine kinase and thereby increases binding of MUC1 and beta -catenin. In the present work, coimmunoprecipitation studies demonstrate that MUC1 associates constitutively with the epidermal growth factor receptor (EGF-R) in human ZR-75-1 breast carcinoma cells. Immunofluorescence studies show that EGF-R and MUC1 associate at the cell membrane. We also show that the activated EGF-R phosphorylates the MUC1 cytoplasmic tail on tyrosine at a YEKV motif that functions as a binding site for the c-Src SH2 domain. The results demonstrate that EGF-R-mediated phosphorylation of MUC1 induces binding of MUC1 to c-Src in cells. Moreover, in vitro and in vivo studies demonstrate that EGF-R increases binding of MUC1 and beta -catenin. These findings support a novel role for EGF-R in regulating interactions of MUC1 with c-Src and beta -catenin.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Childrens Hosp, Sch Med, Div New Born Med, Boston, MA 02115 USA.
   Univ Calif Davis, Dept Biol Chem, Sacramento, CA 95817 USA.
   Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA.
RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
OI Yu, Wei-Hsuan/0000-0002-1782-3738
FU NCI NIH HHS [CA87421]
NR 20
TC 197
Z9 201
U1 1
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 SEP 21
PY 2001
VL 276
IS 38
BP 35239
EP 35242
DI 10.1074/jbc.C100359200
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 474LU
UT WOS:000171109300005
PM 11483589
ER

PT J
AU Boujaoude, LC
   Bradshaw-Wilder, C
   Mao, CG
   Cohn, J
   Ogretmen, B
   Hannun, YA
   Obeid, LM
AF Boujaoude, LC
   Bradshaw-Wilder, C
   Mao, CG
   Cohn, J
   Ogretmen, B
   Hannun, YA
   Obeid, LM
TI Cystic fibrosis transmembrane regulator regulates uptake of sphingoid
   base phosphates and lysophosphatidic acid - Modulation of cellular
   activity of spingosine 1-phosphate
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; COUPLED RECEPTOR EDG-1;
   SACCHAROMYCES-CEREVISIAE; GENE; SPHINGOSINE-1-PHOSPHATE; RESISTANCE;
   IDENTIFICATION; EXPRESSION; CANCER; CELLS
AB Sphingolipids have been implicated in the regulation of cell growth, differentiation, and programmed cell death. Sphingosine 1-phosphate (SPP) has recently emerged as an important lipid messenger and a ligand for the endothelial differentiation gene receptor family of proteins through which it mediates its biologic effects. Recent studies in Saccharomyces cerevisiae in our laboratory implicated the yeast oligomycin resistance gene (YOR1), a member of the ATP binding cassette family of proteins, in the transport of SPP. The cystic fibrosis transmembrane regulator is a unique member of the ATP binding cassette transporter family and has high homology with YOR1. We therefore set out to investigate if this member of the family can regulate SPP transport. We demonstrate that C127/cystic fibrosis transmembrane regulator (CFTR) cells, expressing wild type CFTR, exhibited significantly higher uptake of sphingosine 1-phosphate than either cells expressing a mutant CFTR C127/Delta F508 or C127/mock-transfected cells. This effect was specific, dose-dependent, and competed off by dihydrosphingosine 1-phosphate and lysophosphatidic acid. There was no difference in uptake of sphingosine, C16-ceramide, sphingomyelin, lysophingomyelin, phosphatidylcholine, lysophosphatidylcholine, or phosphatidic acid among the different cell lines. Pretreatment with forskolin or isobutylmethylxanthine to stimulate cAMP did not affect the uptake in any of the cell lines. Moreover, we found that mitogen-activated protein kinase activation by SPP was less responsive in C127/CFTR as compared with C127/mock-transfected cells, suggesting that uptake of SPP by CFTR may divert it from interacting with its cell surface receptors and attenuate signaling functions. Taken together, these data implicate CFTR in uptake of SPP and the related phosphorylated lipids dihydrosphingosine 1-phosphate and lysophosphatidic acid. This uptake influences the availability of SPP to modulate biologic activity via endothelial differentiation gene receptors. These studies may have important implications to cystic fibrosis.
C1 Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA.
   Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA.
   Med Univ S Carolina, Div Pediat Gastroenterol & Nutr, Charleston, SC 29425 USA.
   Ralph H Johnson Vet Adm Hosp, Div Gen Internal Med, Charleston, SC 29401 USA.
   Duke Univ, Med Ctr, Dept Internal Med, Durham, NC 27710 USA.
RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, Div Gen Internal Med, 114 Doughty St,Rm 604 STB,POB 250779, Charleston, SC 29425 USA.
FU NIGMS NIH HHS [R01-GM43825, R01-GM62887]
NR 29
TC 100
Z9 100
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 SEP 21
PY 2001
VL 276
IS 38
BP 35258
EP 35264
DI 10.1074/jbc.M105442200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 474LU
UT WOS:000171109300009
PM 11443135
ER

PT J
AU Yehia, G
   Schlotter, F
   Razavi, R
   Alessandrini, A
   Molina, CA
AF Yehia, G
   Schlotter, F
   Razavi, R
   Alessandrini, A
   Molina, CA
TI Mitogen-activated protein kinase phosphorylates and targets inducible
   cAMP early repressor to ubiquitin-mediated destruction
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ELEMENT-BINDING PROTEIN; CYCLIC-AMP; GENE-EXPRESSION; TRANSCRIPTION
   FACTORS; MICE LACKING; CELL-CYCLE; MAP KINASE; CREM GENE; ICER; PATHWAY
AB Inducible cAMP early repressor (ICER) is an important mediator of cAMP antiproliferative activity that acts as a putative tumor suppressor gene product. In this study, we examined the regulation of ICER protein by phosphorylation and ubiquitination in human choriocarcinoma JEG-3 and mouse pituitary AtT20 cells. We found that cAMP stabilized ICER protein by inhibiting the mitogen-activated protein kinase (MAPK) cascade. Activation of the MAPK pathway increased ICER phosphorylation. ICER phosphorylation was abrogated by inhibition of the MAPK pathway either by cAMP or directly by the MAPK inhibitor PD098059. The MAPKs extracellular signal-regulated kinases 1 and 2 physically interact with ICER and mediated the phosphorylation of ICER on a critical serine residue (Ser-41). A mutant form of ICER in which Ser-41 was substituted by alanine had a half-life 4-5 h longer than its wild-type counterpart. This alteration in stability was due to the inability of the Ser-41-mutant ICER to be efficiently ubiquitinated and degraded via the ubiquitin-proteasome pathway. These results present a novel cell signaling crosstalk mechanism at the cell nucleus between the MAPK and cAMP pathways, whereby MAPK targets a repressor of the cAMP-dependent gene expression for ubiquitination and proteasomal degradation.
C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet Gynecol & Womens Hlth, Newark, NJ 07103 USA.
   Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA.
   Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA.
RP Molina, CA (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Obstet Gynecol & Womens Hlth, 185 S Orange Ave, Newark, NJ 07103 USA.
FU NCI NIH HHS [CA69316]
NR 42
TC 37
Z9 37
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 SEP 21
PY 2001
VL 276
IS 38
BP 35272
EP 35279
DI 10.1074/jbc.M105404200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 474LU
UT WOS:000171109300011
PM 11466319
ER

PT J
AU Jonas, JC
   Laybutt, DR
   Steil, GM
   Trivedi, N
   Pertusa, JG
   Van de Casteele, M
   Weir, GC
   Henquin, JC
AF Jonas, JC
   Laybutt, DR
   Steil, GM
   Trivedi, N
   Pertusa, JG
   Van de Casteele, M
   Weir, GC
   Henquin, JC
TI High glucose stimulates early response gene c-Myc expression in rat
   pancreatic beta cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INSULIN-SECRETION; CHRONIC HYPERGLYCEMIA; TRANSCRIPTION FACTOR; GROWTH;
   ACTIVATION; APOPTOSIS; ISLETS; INHIBITION; RELEASE; TARGET
AB Glucose-induced insulin secretion from hyperglycemic 90% pancreatectomized rats is markedly impaired, possibly because of loss of beta cell differentiation. Association of these changes with beta cell hypertrophy, increased mRNA levels of the transcription factor c-Myc, and their complete normalization by phlorizin treatment suggested a link between chronic hyperglycemia, increased c-Myc expression, and altered beta cell function. In this study, we tested the effect of hyperglycemia on rat pancreatic islet c-Myc expression both in vivo and in vitro. Elevation of plasma glucose for 1-4 days (glucose infusion/clamp) was followed by parallel increases in islet mRNA levels (relative to TATA-binding protein) of c-Myc and two of its target genes, ornithine decarboxylase and lactate dehydrogenase A. Similar changes were observed in vitro upon stimulation of cultured islets or purified beta cells with 20 and 30 mmol(.)liter(-1) glucose for 18 h. These effects of high glucose were reproduced by high potassium-induced depolarization or dibutyryl-cAMP and were inhibited by agents decreasing cytosolic Ca2+ or cAMP concentrations. In conclusion, the expression of the early response gene c-Myc in rat pancreatic beta cells is stimulated by high glucose in a Ca2+ -dependent manner and by cAMP. c-Myc could therefore participate to the regulation of beta cell growth, apoptosis, and differentiation under physiological or pathophysiological conditions.
C1 Univ Catholique Louvain, Unit Endocrinol & Metab, B-1200 Brussels, Belgium.
   Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA.
   Free Univ Brussels, Diabet Res Ctr, Brussels, Belgium.
RP Jonas, JC (reprint author), Ave Hippocrate 55, B-1200 Brussels, Belgium.
RI Jonas, Jean-Christophe/C-6766-2011
OI Jonas, Jean-Christophe/0000-0001-9882-5438
FU NIDDK NIH HHS [DK-35449]
NR 35
TC 74
Z9 77
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 SEP 21
PY 2001
VL 276
IS 38
BP 35375
EP 35381
DI 10.1074/jbc.M105020200
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 474LU
UT WOS:000171109300024
PM 11457846
ER

PT J
AU Nishiyama, R
   Sakaguchi, T
   Kinugasa, T
   Gu, XB
   MacDermott, RP
   Podolsky, DK
   Reinecker, HC
AF Nishiyama, R
   Sakaguchi, T
   Kinugasa, T
   Gu, XB
   MacDermott, RP
   Podolsky, DK
   Reinecker, HC
TI Interleukin-2 receptor beta subunit-dependent and -independent
   regulation of intestinal epithelial tight junctions
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID INFLAMMATORY-BOWEL-DISEASE; INTEGRAL MEMBRANE-PROTEIN; ACTIVATED
   KILLER-CELLS; TYROSINE PHOSPHORYLATION; INTRAEPITHELIAL LYMPHOCYTES;
   BARRIER FUNCTION; POSSIBLE INVOLVEMENT; ULCERATIVE-COLITIS;
   CROHNS-DISEASE; DIRECT BINDING
AB Interleukin (IL)-15 is able to regulate tight junction formation in intestinal epithelial cells. However, the mechanisms that regulate the intestinal barrier function in response to IL-15 and the involved subunits of the IL-15 ligand-receptor system are unknown. We determined the IL-2R beta subunit and IL-15-dependent regulation of tight junction-associated proteins in the human intestinal epithelial cell line T-84. The IL-2R beta subunit was expressed and induced signal transduction in caveolin enriched rafts in intestinal epithelial cells. IL-15-mediated tightening of intestinal epithelial monolayers correlated with the enhanced recruitment of tight junction proteins into Triton X-100-insoluble protein fractions. IL-15-mediated up-regulation of ZO-1 and ZO-2 expression was independent of the IL-2R beta subunit, whereas the phosphorylation of occludin and enhanced membrane association of claudin-1 and claudin-2 by IL-15 required the presence of the IL-2R beta subunit. Recruitment of claudins and hyperphosphorylated occludin into tight junctions resulted in a more marked induction of tight junction formation in intestinal epithelial cells than the up-regulation of ZO-1 and ZO-2 by itself. The regulation of the intestinal epithelial barrier function by IL-15 involves IL-2R beta -dependent and -independent signaling pathways leading to the recruitment of claudins, hyperphosphorylated occludin, ZO-1, and ZO-2 into the tight junctional protein complex.
C1 Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02114 USA.
   Albany Med Coll, Div Gastroenterol, Albany, NY 12208 USA.
RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Dept Med, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Jackson Bldg R711,32 Fruit St, Boston, MA 02114 USA.
FU NIDDK NIH HHS [DK 54427, DK 21474, DK 41557, DK 43351, DK 51003, P01 DK
   33506]
NR 70
TC 50
Z9 51
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 SEP 21
PY 2001
VL 276
IS 38
BP 35571
EP 35580
DI 10.1074/jbc.M106013200
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 474LU
UT WOS:000171109300050
PM 11466322
ER

PT J
AU Choudhury, GG
AF Choudhury, GG
TI Akt serine threonine kinase regulates platelet-derived growth
   factor-induced DNA synthesis in glomerular mesangial cells - Regulation
   of c-fos and p27(kip1) gene expression
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; BREAST-CANCER CELLS; DEPENDENT KINASE;
   PHOSPHATIDYLINOSITOL 3-KINASE; INHIBITOR P27(KIP1); INDUCED
   PHOSPHORYLATION; PDGF RECEPTOR; CYCLIN D1; SURVIVAL; RAS
AB Proliferation of mesangial cells requires platelet-derived growth factor receptor beta (PDGFR)-mediated signal transduction. We have previously shown that activation of phosphatidylinositol (PI) 3-kinase is necessary for PDGFR-induced DNA synthesis in these cells. The mechanism by which PI 3-kinase stimulates DNA synthesis is not known. One target of PI 3-kinase, Akt serine threonine kinase, regulates survival of many cells by inhibiting the actions of certain proapoptotic proteins. In this study, we investigated the role of Akt in PDGF-induced DNA synthesis in mesangial cells. PDGF increased Akt serine threonine kinase activity in a time- and PI 3-kinase-dependent manner. Expression of dominant negative Akt by adenovirus-mediated gene transfer blocked PDGF-induced activation of endogenous Akt in mesangial cells, resulting in complete inhibition of DNA synthesis. On the other hand, inhibition of MAPK attenuated PDGF-induced DNA synthesis only partially. Inhibition of Akt also attenuated PDGF-induced c-fos gene transcription, with concomitant inhibition of Elk-1-dependent transcription, indicating positive regulation of this early response gene by Akt. To further determine the role of Akt in PDGF-induced DNA Synthesis, we investigated its effect on cyclin-dependent kinase 2 (CDK2). PDGF stimulated CDK2 activity in mesangial cells and decreased the level of p27(kip1) cyclin kinase inhibitor protein. Expression of dominant negative Akt increased p27(kip1) protein and resulted in inhibition of CDK2 activity. The increase in p27(kip1) expression in response to Akt kinase inhibition was due to increased transcription of the p27(kip1) gene. p27(kip1) transcription similarly was decreased by expression of constitutively active Akt kinase in mesangial cells. These data provide the first evidence that Akt kinase regulates PDGF-induced DNA synthesis by regulating CDK2 activity and define Akt-mediated inhibition of transcription of p27(kip1) as one of the mechanisms for PDGF-induced DNA synthesis in mesangial cells.
C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA.
   S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA.
RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
FU NIDDK NIH HHS [DK-50190, DK-55815]
NR 74
TC 66
Z9 67
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 SEP 21
PY 2001
VL 276
IS 38
BP 35636
EP 35643
DI 10.1074/jbc.M100946200
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 474LU
UT WOS:000171109300058
PM 11470779
ER

PT J
AU Williams, JA
   Su, HS
   Bernards, A
   Field, J
   Sehgal, A
AF Williams, JA
   Su, HS
   Bernards, A
   Field, J
   Sehgal, A
TI A circadian output in Drosophila mediated by neurofibromatosis-1 and
   Ras/MAPK
SO SCIENCE
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; PATHWAY; CLOCK; RAS; SEVENLESS; RHYTHMS; SON;
   PHOSPHORYLATION; MELANOGASTER; GENES
AB Output from the circadian clock controls rhythmic behavior through poorly understood mechanisms. In Drosophila, null mutations of the neurofibromatosis-1 (Nf1) gene produce abnormalities of circadian rhythms in locomotor activity. Mutant flies show normal oscillations of the clock genes period (per) and timeless (tim) and of their corresponding proteins, but altered oscillations and levels of a clock-controlled reporter. Mitogen-activated protein kinase (MAPK) activity is increased in Nf1 mutants, and the circadian phenotype is rescued by loss-of-function mutations in the Ras/MAPK pathway. Thus, Nf1 signals through Ras/MAPK in Drosophila. Immunohistochemical staining revealed a circadian oscillation of phospho-MAPK in the vicinity of nerve terminals containing pigment-dispersing factor (PDF), a secreted output from clock cells, suggesting a coupling of PDF to Ras/MAPK signaling.
C1 Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA.
   Univ Penn, Sch Med, Ctr Sleep & Resp Neurobiol, Philadelphia, PA 19104 USA.
   Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA.
   Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
RP Sehgal, A (reprint author), Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA.
NR 26
TC 133
Z9 139
U1 0
U2 13
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD SEP 21
PY 2001
VL 293
IS 5538
BP 2251
EP 2256
DI 10.1126/science.1063097
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 475AL
UT WOS:000171139400043
PM 11567138
ER

PT J
AU Griffiths, EK
   Krawczyk, C
   Kong, YY
   Raab, M
   Hyduk, SJ
   Bouchard, D
   Chan, VS
   Kozieradzki, I
   Oliveira-Dos-Santos, AJ
   Wakeham, A
   Ohashi, PS
   Cybulsky, MI
   Rudd, CE
   Penninger, JM
AF Griffiths, EK
   Krawczyk, C
   Kong, YY
   Raab, M
   Hyduk, SJ
   Bouchard, D
   Chan, VS
   Kozieradzki, I
   Oliveira-Dos-Santos, AJ
   Wakeham, A
   Ohashi, PS
   Cybulsky, MI
   Rudd, CE
   Penninger, JM
TI Positive regulation of T cell activation and integrin adhesion by the
   adapter Fyb/Slap
SO SCIENCE
LA English
DT Article
ID INTERLEUKIN-2 PRODUCTION; ENA/VASP PROTEINS; TYROSINE KINASES;
   IMMUNE-SYSTEM; DRIVING-FORCE; RECEPTOR; SLP-76; FYN; SLAP-130; CLONING
AB The molecular adapter Fyb/Slap regulates signaling downstream of the T cell receptor (TCR), but whether it plays a positive or negative role is controversial. We demonstrate that Fyb/Slap-deficient T cells exhibit defective proliferation and cytokine production in response to TCR stimulation. Fyb/Slap is also required in vivo for T cell-dependent immune responses. Functionally, Fyb/Slap has no apparent role in the activation of known TCR signaling pathways, F-actin polymerization, or TCR clustering. Rather, Fyb/Slap regulates TCR-induced integrin clustering and adhesion. Thus, Fyb/Slap is the first molecular adapter to be identified that couples TCR stimulation to the avidity modulation of integrins governing T cell adhesion.
C1 Amgen Inst, Toronto, ON M5G 2C1, Canada.
   Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M9, Canada.
   Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M9, Canada.
   Univ Toronto, Dept Immunol, Toronto, ON M5G 2M9, Canada.
   Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   Univ Toronto, Toronto Gen Hosp, Res Inst, Dept Lab Med & Pathobiol, Toronto, ON M5G 1L7, Canada.
RP Penninger, JM (reprint author), Amgen Inst, 620 Univ Ave, Toronto, ON M5G 2C1, Canada.
RI Penninger, Josef/I-6860-2013
OI Penninger, Josef/0000-0002-8194-3777
NR 26
TC 216
Z9 221
U1 0
U2 6
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
J9 SCIENCE
JI Science
PD SEP 21
PY 2001
VL 293
IS 5538
BP 2260
EP 2263
DI 10.1126/science.1063397
PG 4
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 475AL
UT WOS:000171139400045
PM 11567140
ER

PT J
AU Teixeira, CA
   Sena-Esteves, M
   Lopes, L
   Miranda, MCS
   Ribeiro, MG
AF Teixeira, CA
   Sena-Esteves, M
   Lopes, L
   Miranda, MCS
   Ribeiro, MG
TI Retrovirus-mediated transfer and expression of beta-hexosaminidase
   alpha-chain cDNA in human fibroblasts from G(M2)-gangliosidosis B1
   variant
SO HUMAN GENE THERAPY
LA English
DT Article
ID TAY-SACHS-DISEASE; GENE-TRANSFER; CULTURED FIBROBLASTS; ACTIVATOR
   PROTEIN; LYSOSOMAL-ENZYMES; CELLS; GM2-GANGLIOSIDOSIS; BIOSYNTHESIS;
   GENERATION; DEFECT
AB Mutations in the alpha -chain of lysosomal hexosaminidase (EC 3.2.1.52) underlie two distinct biochemical phenotypes known as variant B and variant B1 of G(M2) gangliosidosis. This paper shows that the transduction of human B1-type fibroblasts (producing catalytically inactive alpha -chains) with a retroviral vector encoding the human hexosaminidase alpha -chain leads to a complete correction of HexA (alpha beta dimer) activity with both synthetic and natural substrates. The alpha -subunit overexpression leads to a partial HexB (beta beta dimer) depletion corresponding to about 10% of control HexB activity. The newly synthesized enzyme is correctly processed and targeted to the lysosomes in transduced cells. The high levels of recombinant enzyme correctly produced the metabolic defect, enabling the cells efficiently to degrade the accumulated storage product present in lysosomes. The transduced fibroblasts are also able to secrete HexA efficiently into the culture medium. Moreover, transfer of the human transgene product to B1-type deficient fibroblasts lead to an increase of activity against 4MUGS, the alpha -chain specific synthetic substrate, up to 30% of the control mean activity level. This level of activity might be sufficient to restore the normal ganglioside G(M2) metabolism in recipient cells. The data obtained demonstrate that B1-type phenotype can be efficiently corrected by retrovirus-mediated gene transfer.
C1 Inst Biol Mol & Celular, Unidade Neurobiol Genet, P-4150180 Oporto, Portugal.
   Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA.
   Inst Med Genet, Unidade Enzimol, Oporto, Portugal.
RP Ribeiro, MG (reprint author), Inst Biol Mol & Celular, Unidade Neurobiol Genet, R Campo Alegre 823, P-4150180 Oporto, Portugal.
RI sa Miranda, Maria Clara/K-3920-2013; Ribeiro, Maria Gil/B-6467-2013; 
OI sa Miranda, Maria Clara/0000-0003-0123-5525; Ribeiro, Maria
   Gil/0000-0001-9365-6057; Teixeira, Carla/0000-0001-6277-6400
NR 28
TC 9
Z9 9
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 SEP 20
PY 2001
VL 12
IS 14
BP 1771
EP 1783
DI 10.1089/104303401750476267
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA 475UH
UT WOS:000171186100006
PM 11560770
ER

PT J
AU Moberg, KH
   Bell, DW
   Wahrer, DCR
   Haber, DA
   Hariharan, IK
AF Moberg, KH
   Bell, DW
   Wahrer, DCR
   Haber, DA
   Hariharan, IK
TI Archipelago regulates Cyclin E levels in Drosophila and is mutated in
   human cancer cell lines
SO NATURE
LA English
DT Article
ID EYE IMAGINAL DISC; CONTROLS S-PHASE; F-BOX; PROLIFERATION; EXPRESSION;
   PROTEINS; ELEGANS; BREAST; ARREST; FAMILY
AB During Drosophila development and mammalian embryogenesis, exit from the cell cycle is contingent on tightly controlled downregulation of the activity of Cyclin E-Cdk2 complexes that normally promote the transition from G1 to S phase(1,2). Although protein degradation has a crucial role in downregulating levels of Cyclin E, many of the proteins that function in degradation of Cyclin E have not been identified. In a screen for Drosophila mutants that display increased cell proliferation, we identified archipelago, a gene encoding a protein with an F-box and seven tandem WD (tryptophan-aspartic acid) repeats. Here we show that archipelago mutant cells have persistently elevated levels of Cyclin E protein without increased levels of cyclin E RNA. They are under-represented in G1 fractions and continue to proliferate when their wild-type neighbours become quiescent. The Archipelago protein binds directly to Cyclin E and probably targets it for ubiquitin-mediated degradation. A highly conserved human homologue is present and is mutated in four cancer cell lines including three of ten derived from ovarian carcinomas. These findings implicate archipelago in developmentally regulated degradation of Cyclin E and potentially in the pathogenesis of human cancers.
C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA.
NR 22
TC 316
Z9 329
U1 0
U2 5
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 20
PY 2001
VL 413
IS 6853
BP 311
EP 316
DI 10.1038/35095068
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 473KB
UT WOS:000171040500040
PM 11565033
ER

PT J
AU Hideshima, T
   Nakamura, N
   Chauhan, D
   Anderson, KC
AF Hideshima, T
   Nakamura, N
   Chauhan, D
   Anderson, KC
TI Biologic sequelae of interleukin-6 induced P13-K/Akt signaling in
   multiple myeloma
SO ONCOGENE
LA English
DT Article
DE multiple myeloma; IL-6; SHP2; P13-K; Akt; apoptosis; caspase-9
ID PROTEIN-KINASE-B; DEXAMETHASONE-INDUCED APOPTOSIS; PLECKSTRIN-HOMOLOGY
   DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE/AKT; CELL-GROWTH; TRANSDUCTION
   PATHWAY; INHIBITS APOPTOSIS; PLASMA-CELLS; PHOSPHORYLATION; ACTIVATION
AB Previous studies demonstrate that interleukin-6 (IL-6) mediates growth and survival in human multiple myeloma (MM) cells via the MEK/MAPK and JAK/STAT signaling pathways, respectively. IL-6 also confers protection against Dexamethasone (Dex)-induced apoptosis via activation of protein tyrosine phosphatase (SHP2). In the current study, we characterized IL-6 triggered phophatidylinositol-3 kinase/Akt kinase (PI3K/Akt) signaling in MM cells. IL-6 induces Akt/PKB phosphorylation in a time and dose dependent manner in MMAS MM cells. IL-6 also induced phosphorylation of downstream targets of Akt, including Bad, GSK-3 beta, and FKHR, confirming Akt activation. Inhibition of Akt activation by the PI3-K inhibitor LY294002 partially blocked IL-6 triggered MEK/MAPK activation and proliferation in MMAS cells, suggesting cross-talk between PI3-K and MEK signaling. We demonstrate that Dex-induced apoptosis in MM.1S cells is mediated by downstream activation of caspase-9, with resultant caspase-3 cleavage; and conversely, that IL-6 triggers activation of PI3-K and its association with SHP2, inactivates caspase-9, and protects against Dex-induced apoptosis. LY294002 completely abrogates this signaling cascade, further confirming the importance of PI3-K/Akt signaling in conferring the protective effect of IL-6 against Dex-induced apoptosis. Finally, we show that IL-6 triggered PI3-K/Akt signaling in MMAS cells inactivates forkhead transcriptional factor (FKHR), with related G1/S phase transition, whereas LY294002 blocks this signaling, resulting in upregulation of p27(KIPI) and G1 growth arrest. Our data therefore suggest that PI3-K/ Akt signaling mediates growth, survival, and cell cycle regulatory effects of IL-6 in MM.
C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, M557,44 Binney St, Boston, MA 02115 USA.
FU NIMH NIH HHS [P01 MH 78378, R01 MH 50947]
NR 50
TC 315
Z9 323
U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD SEP 20
PY 2001
VL 20
IS 42
BP 5991
EP 6000
DI 10.1038/sj.onc.1204833
PG 10
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 473QF
UT WOS:000171056300006
PM 11593406
ER

PT J
AU Chantarujikapong, SI
   Scherrer, JF
   Xian, H
   Eisen, SA
   Lyons, MJ
   Goldberg, J
   Tsuang, M
   True, WR
AF Chantarujikapong, SI
   Scherrer, JF
   Xian, H
   Eisen, SA
   Lyons, MJ
   Goldberg, J
   Tsuang, M
   True, WR
TI A twin study of generalized anxiety disorder symptoms, panic disorder
   symptoms and post-traumatic stress disorder in men
SO PSYCHIATRY RESEARCH
LA English
DT Article
DE twin study; anxiety disorder; panic disorder; post-traumatic stress
ID NATIONAL-COMORBIDITY-SURVEY; PSYCHIATRIC-DISORDERS; GENETIC-FACTORS; VET
   REGISTRY; POPULATION; FAMILY; TELEPHONE; LIFETIME; VETERANS; ATTACKS
AB Generalized anxiety disorder (GAD), panic disorder (PD) and post-traumatic stress disorder (PTSD) often co-occur. We investigated whether and to what degree genetic and environmental contributions overlap among symptoms of GAD, symptoms of PD and PTSD. Subjects were 3327 monozygotic and dizygotic male-male twin pair members of the Vietnam Era Twin Registry who participated in a 1992 telephone administration of the Diagnostic Interview Schedule Version 3 Revised (DIS3R). Genetic model fitting was performed to estimate the magnitude of genetic and environmental contributions to the lifetime co-occurrence of GAD symptoms, PD symptoms and PTSD. The liability for GAD symptoms was due to a 37.9% additive genetic contribution common to PD symptoms and PTSD. Liability for PD symptoms was clue to a 20.7% additive genetic contribution common to GAD symptoms and PTSD, and a 20.1% additive genetic influence specific to PD symptoms. Additive genetic influences common to symptoms of GAD and PD accounted for 21.3% of the genetic variance in PTSD. Additive genetic influences specific to PTSD accounted for 13.6% of the genetic variance in PTSD. Remaining variance for all three disorders was due to unique environmental factors both common and specific to each phenotype. These results suggest that these disorders each have etiologically distinct components and also have significant genetic and unique environmental contributions in common. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
C1 St Louis VAMC, Res Serv 151 JC, St Louis, MO 63106 USA.
   St Louis Univ, Hlth Sci Ctr, Sch Publ Hlth, St Louis, MO 63108 USA.
   Washington Univ, Sch Med, Div Gen Med Sci, Dept Internal Med, St Louis, MO USA.
   St Louis VAMC, Med Serv, St Louis, MO 63106 USA.
   Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA 02401 USA.
   Boston Univ, Dept Psychol, Boston, MA 02215 USA.
   US Dept Vet Affairs, Hlth Serv Res & Dev & Cooperat Studies Program, Hines, IL 60141 USA.
   Univ Illinois, Sch Publ Hlth, Program Epidemiol, Chicago, IL USA.
   Harvard Univ, Sch Publ Hlth, Training Program Psychiat Epidemiol & Biostat, Boston, MA 02115 USA.
RP True, WR (reprint author), St Louis VAMC, Res Serv 151 JC, 915 N Grand Blvd, St Louis, MO 63106 USA.
RI Lyons, Michael/B-6119-2011; 
OI Lyons, Michael/0000-0001-6516-9219
FU NIAAA NIH HHS [AA07728, AA10339, AA11822]; NIDA NIH HHS [DA00272,
   DA4604, DAO72261-01]; NIMH NIH HHS [MH-37685, MH-31302]
NR 42
TC 77
Z9 79
U1 1
U2 5
PU ELSEVIER SCI IRELAND LTD
PI CLARE
PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE,
   IRELAND
SN 0165-1781
J9 PSYCHIAT RES
JI Psychiatry Res.
PD SEP 20
PY 2001
VL 103
IS 2-3
BP 133
EP 145
DI 10.1016/S0165-1781(01)00285-2
PG 13
WC Psychiatry
SC Psychiatry
GA 477BA
UT WOS:000171262200004
PM 11549402
ER

PT J
AU Levinsky, NG
   Yu, W
   Ash, A
   Moskowitz, M
   Gazelle, G
   Saynina, O
   Emanuel, EJ
AF Levinsky, NG
   Yu, W
   Ash, A
   Moskowitz, M
   Gazelle, G
   Saynina, O
   Emanuel, EJ
TI Influence of age on medicare expenditures and medical care in the last
   year of life
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID ILL HOSPITALIZED ADULTS; SERIOUSLY ILL; DEATH; MORBIDITY; DECISIONS
AB Context Expenditures for Medicare beneficiaries in the last year of life decrease with increasing age. The cause of this phenomenon is uncertain.
   Objectives To examine this pattern in detail and evaluate whether decreases in aggressiveness of medical care explain the phenomenon.
   Design, Setting, and Patients Analysis of sample Medicare data for beneficiaries aged 65 years or older from Massachusetts (n=34131) and California (n=19064) who died in 1996.
   Main Outcome Measure Medical expenditures during the last year of life, analyzed by age group, sex, race, place and cause of death, comorbidity, and use of hospital services.
   Results For Massachusetts and California, respectively, Medicare expenditures per beneficiary were $35300 and $27800 among those aged 65 through 74 years vs $22000 and $21600 for those aged 85 years or older. The pattern of decreasing Medicare expenditures with age is pervasive, persisting throughout the last year of life in both states for both sexes, for black and white beneficiaries, for persons with varying levels of comorbidity, and for those receiving hospice vs conventional care, regardless of cause and site of death. The aggressiveness of medical care in both Massachusetts and California also decreased with age, as judged by less frequent hospital and intensive care unit admissions and by markedly decreasing use of cardiac catheterization, dialysis, ventilators, and pulmonary artery monitors, regardless of cause of death. Decrease in the cost of hospital services accounts for approximately 80% of the decrease in Medicare expenditures with age in both states.
   Conclusions Medicare expenditures in the last year of life decrease with age, especially for those aged 85 years or older. This is in large part because the aggressiveness of medical care in the last year of life decreases with increasing age.
C1 Boston Univ, Med Ctr, Sch Med, Dept Med,Sect Gen Internal Med,Hlth Care Res Unit, Boston, MA 02118 USA.
   US Dept Vet Affairs, Hlth Econ Resource Ctr Hlth Sci, Res Serv, Menlo Pk, CA USA.
   US Dept Vet Affairs, Hlth Econ Resource Ctr Hlth Sci, Dev Serv, Menlo Pk, CA USA.
   US Dept Vet Affairs, Ctr Cooperat Studies Hlth Serv, Menlo Pk, CA USA.
   Harvard Vanguard Med Associates, Palliat & Support Med Program, Boston, MA USA.
   Natl Bur Econ Res, Palo Alto, CA USA.
   NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA.
RP Levinsky, NG (reprint author), Boston Univ, Med Ctr, Sch Med, Dept Med,Sect Gen Internal Med,Hlth Care Res Unit, 715 Albany St, Boston, MA 02118 USA.
NR 14
TC 121
Z9 121
U1 0
U2 1
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 SEP 19
PY 2001
VL 286
IS 11
BP 1349
EP 1355
DI 10.1001/jama.286.11.1349
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 473DJ
UT WOS:000171024500028
PM 11560540
ER

PT J
AU Whiting, P
   Bagnall, AM
   Sowden, AJ
   Cornell, JE
   Mulrow, CE
   Ramirez, G
AF Whiting, P
   Bagnall, AM
   Sowden, AJ
   Cornell, JE
   Mulrow, CE
   Ramirez, G
TI Interventions for the treatment and management of chronic fatigue
   syndrome - A systematic review
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID RANDOMIZED CONTROLLED TRIAL; PLACEBO-CONTROLLED TRIAL;
   COGNITIVE-BEHAVIOR THERAPY; LOW-DOSE HYDROCORTISONE; ESSENTIAL
   FATTY-ACIDS; DOUBLE-BLIND; INTRAVENOUS IMMUNOGLOBULIN; MYALGIC
   ENCEPHALOMYELITIS; CROSSOVER TRIAL; GRADED-EXERCISE
AB Context A variety of interventions have been used in the treatment and management of chronic fatigue syndrome (CFS). Currently, debate exists among health care professionals and patients about appropriate strategies for management.
   Objective To assess the effectiveness of all interventions that have been evaluated for use in the treatment or management of CFS in adults or children.
   Data Sources Nineteen specialist databases were searched from inception to either January or July 2000 for published or unpublished studies in any language. The search was updated through October 2000 using PubMed. Other sources included scanning citations, Internet searching, contacting experts, and online requests for articles.
   Study Selection Controlled trials (randomized or non randomized) that evaluated interventions inpatients diagnosed as having CFS according to any criteria were included. Study inclusion was assessed independently by 2 reviewers. Of 350 studies initially identified, 44 met inclusion criteria, including 36 randomized controlled trials and 8 controlled trials.
   Data Extraction Data extraction was conducted by 1 reviewer and checked by a second. Validity assessment was carried out by 2 reviewers with disagreements resolved by consensus. A qualitative synthesis was carried out and studies were grouped according to type of intervention and outcomes assessed.
   Data Synthesis The number of participants included in each trial ranged from 12 to 326, with a total of 2801 participants included in the 44 trials combined. Across the studies, 38 different outcomes were evaluated using about 130 different scales or types of measurement. Studies were grouped into 6 different categories. In the behavioral category, graded exercise therapy and cognitive behavioral therapy showed positive results and also scored highly on the validity assessment. In the immunological category, both immunoglobulin and hydrocortisone showed some limited effects but, overall, the evidence was inconclusive. There was insufficient evidence about effectiveness in the other 4 categories (pharmacological, supplements, complementary/alternative, and other interventions).
   Conclusions Overall, the interventions demonstrated mixed results in terms of effectiveness. All conclusions about effectiveness should be considered together with the methodological inadequacies of the studies. Interventions which have shown promising results include cognitive behavioral therapy and graded exercise therapy. Further research into these and other treatments is required using Standardized outcome measures.
C1 Univ York, Natl Hlth Serv Ctr Reviews & Disseminat, York YO10 5DD, N Yorkshire, England.
   Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio Evidence Based Practice Ctr, San Antonio, TX 78284 USA.
   S Texas Vet Hlth Care Syst, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA.
   S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA.
RP Whiting, P (reprint author), Univ York, Natl Hlth Serv Ctr Reviews & Disseminat, York YO10 5DD, N Yorkshire, England.
FU PHS HHS [290-97-0012]
NR 57
TC 267
Z9 271
U1 1
U2 34
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 SEP 19
PY 2001
VL 286
IS 11
BP 1360
EP 1368
DI 10.1001/jama.286.11.1360
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 473DJ
UT WOS:000171024500030
PM 11560542
ER

PT J
AU Hylek, EM
   Regan, S
   Go, AS
   Hughes, RA
   Singer, DE
   Skates, SJ
AF Hylek, EM
   Regan, S
   Go, AS
   Hughes, RA
   Singer, DE
   Skates, SJ
TI Clinical predictors of prolonged delay in return of the international
   normalized ratio to within the therapeutic range after excessive
   anticoagulation with warfarin
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID RISK-FACTORS; BLEEDING COMPLICATIONS; DRUG-METABOLISM; PROTEIN-BINDING;
   AGE; LIVER; DISCONTINUATION; OUTPATIENTS; CLEARANCE
AB Background: An elevated international normalized ratio (INR) increases the risk for major hemorrhage during warfarin therapy. Optimal management of patients with asymptomatic elevations in INR is hampered by the lack of understanding of the time course of INR decay after cessation of warfarin therapy.
   Objective: To identify predictors of the rate of INR normalization after excessive anticoagulation.
   Design: Retrospective cohort study.
   Setting: Outpatient anticoagulant therapy unit.
   Patients: Outpatients with an INR greater than 6.0 were identified from August 1993 to September 1998. Patients in whom two doses of warfarin were withheld and a follow-up INR was obtained on the second calendar day were enrolled. No patient received vitamin K-tau.
   Measurements: The INR was measured 2 days after an INR greater than 6.0 was recorded.
   Results: Of 633 study patients with an initial INR greater than 6.0, 232 (37%) still had an INR of 4.0 or greater after two doses of warfarin were withheld. Patients who required larger weekly maintenance doses of warfarin were less likely to have an INR of 4.0 or greater on day 2 (adjusted odds ratio per 10 mg of warfarin, 0.87 [95% Cl, 0.79 to 0.97]). Other risk factors for having an INR of 4.0 or greater on day 2 included age (odds ratio per decade of life, 1.18 [Cl, 1.01 to 1.38]), index INR (odds ratio per unit, 1.25 [Cl, 1.14 to 1.37]), decompensated congestive heart failure (odds ratio, 2.79 [Cl, 1.30 to 5.98]), and active cancer (odds ratio, 2.48 [Cl, 1.11 to 5.57]).
   Conclusions: Steady-state warfarin dose, advanced age, and extreme elevation in INR are risk factors for prolonged delay in return of the INR to within the therapeutic range. Decompensated congestive heart failure and active cancer greatly increase this risk.
C1 Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Kaiser Permanente Med Care Program, Oakland, CA USA.
   Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Hylek, EM (reprint author), Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
FU NIA NIH HHS [AG15478]
NR 39
TC 107
Z9 111
U1 0
U2 3
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 SEP 18
PY 2001
VL 135
IS 6
BP 393
EP 400
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 472FH
UT WOS:000170972500001
PM 11560452
ER

PT J
AU Hays, JT
   Hurt, RD
   Rigotti, NA
   Niaura, R
   Gonzales, D
   Durcan, MJ
   Sachs, DPL
   Wolter, TD
   Buist, AS
   Johnston, JA
   White, JD
AF Hays, JT
   Hurt, RD
   Rigotti, NA
   Niaura, R
   Gonzales, D
   Durcan, MJ
   Sachs, DPL
   Wolter, TD
   Buist, AS
   Johnston, JA
   White, JD
TI Sustained-release bupropion for pharmacologic relapse prevention after
   smoking cessation - A randomized, controlled trial
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID NICOTINE PATCH; DEPENDENCE
AB Background: Smoking relapse is common after successful pharmacologic treatment for smoking cessation. No previous studies have examined long-term drug therapy used expressly for prevention of smoking relapse.
   Objective: To evaluate the efficacy of bupropion to prevent smoking relapse.
   Design: Randomized, placebo-controlled trial.
   Participants: 784 healthy community volunteers who were motivated to quit smoking and who smoked at least 15 cigarettes per day.
   Intervention: The participants received open-label, sustained-release bupropion, 300 mg/d, for 7 weeks. Participants who were abstinent throughout week 7 of open-label treatment were randomly assigned to receive bupropion, 300 mg/d, or placebo for 45 weeks and were subsequently followed for an additional year after the conclusion of the medication phase. Participants were briefly counseled at all follow-up visits. At the end of open-label bupropion treatment, 461 of 784 participants (58.8%) were abstinent from smoking.
   Measurement: Self-reported abstinence was confirmed by an expired air carbon monoxide concentration of 10 parts per million or less.
   Results: The point prevalence of smoking abstinence was significantly higher in the bupropion group than in the placebo group at the end (week 52) of drug therapy (55.1% vs. 42.3%, respectively; P = 0.008) and at week 78 (47.7% vs. 37.7%; P = 0.034) but did not differ at the final (week 104) follow-up visit (41.6% vs. 40.0%). The median time to relapse was significantly greater for bupropion recipients than for placebo recipients (156 days vs. 65 days; P = 0.021). The continuous abstinence rate was higher in the bupropion group than in the placebo group at study week 24 (17 weeks after randomization) (52.3% vs. 42.3%; P = 0.037) but did not differ between groups after week 24. Weight gain was significantly less in the bupropion group than in the placebo group at study weeks 52 (3.8 kg vs. 5.6 kg; P = 0.002) and 104 (4.1 kg vs. 5.4 kg; P = 0.016).
   Conclusions: in persons who stopped smoking with 7 weeks of bupropion treatment, sustained-release bupropion for 12 months delayed smoking relapse and resulted in less weight gain.
C1 Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Brown Univ, Providence, RI 02912 USA.
   Oregon Hlth Sci Univ, Portland, OR 97201 USA.
   Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA.
   Palo Alto Ctr Pulm Dis Prevent, Palo Alto, CA USA.
   Stanford Univ, Sch Med, Stanford, CA 94305 USA.
RP Hays, JT (reprint author), Mayo Clin, Nicotine Res Ctr, 200 1st St SW, Rochester, MN 55905 USA.
NR 26
TC 232
Z9 236
U1 3
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 SEP 18
PY 2001
VL 135
IS 6
BP 423
EP 433
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA 472FH
UT WOS:000170972500004
PM 11560455
ER

PT J
AU Mukamal, KJ
   Jadhav, PP
   D'Agostino, RB
   Massaro, JM
   Mittleman, MA
   Lipinska, I
   Sutherland, PA
   Matheney, T
   Levy, D
   Wilson, PWF
   Ellison, RC
   Silbershatz, H
   Muller, JE
   Tofler, GH
AF Mukamal, KJ
   Jadhav, PP
   D'Agostino, RB
   Massaro, JM
   Mittleman, MA
   Lipinska, I
   Sutherland, PA
   Matheney, T
   Levy, D
   Wilson, PWF
   Ellison, RC
   Silbershatz, H
   Muller, JE
   Tofler, GH
TI Alcohol consumption and hemostatic factors Analysis of the Framingham
   Offspring cohort
SO CIRCULATION
LA English
DT Article
DE alcohol; fibrinogen; fibrinolysis; thrombosis; plasminogin activators;
   von Willebrand factor
ID CORONARY HEART-DISEASE; PLASMINOGEN-ACTIVATOR INHIBITOR; ACUTE
   MYOCARDIAL-INFARCTION; VON-WILLEBRAND-FACTOR; RISK-FACTORS;
   PLASMA-FIBRINOGEN; FACTOR-VIII; FIBRINOLYTIC-ACTIVITY;
   PLATELET-AGGREGATION; BODY-WEIGHT
AB Background-Moderate alcohol consumers have lower rates of cardiovascular disease than abstainers. One proposed mechanism is a beneficial effect on hemostatic parameters, but previous studies have provided conflicting results.
   Methods and Results-We measured levels of fibrinogen, plasma viscosity, von Willebrand factor, factor VII, plasminogen activator inhibitor antigen-1, and tissue plasminogen activator antigen in a cross-sectional analysis of 3223 adults free of cardiovascular disease enrolled in the Framingham Offspring Study. We assessed their alcohol consumption with a standardized questionnaire. Light-to-moderate alcohol consumption was associated with lower levels of fibrinogen, plasma viscosity, von Willebrand factor, and factor VII. This association was most pronounced for consumers of 3 to 7 drinks weekly for viscosity and 7 to 21 drinks weekly for the other hemostatic measures. Alcohol intake of 7 to 21 drinks weekly or more was associated with impaired fibrinolytic potential, reflected by higher levels of plasminogen activator inhibitor antigen-1 and tissue plasminogen activator antigen. Wine drinkers had lower plasminogen activator inhibitor antigen-1 levels than other drinkers, particularly at 3 to 21 drinks weekly, but beverage type did not otherwise consistently affect the results.
   Conclusions-Light-to-moderate alcohol consumption is associated with lower levels of coagulatory factors, but higher intake is associated with impaired fibrinolytic potential. These findings are consistent with the hypothesis that a balance between hemostatic and fibrinolytic activity may contribute to the complex relation of alcohol use with coronary heart disease.
C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
   Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA.
   Boston Univ, Dept Math & Stat, Boston, MA USA.
   NHLBI, Framingham Heart Study, Framingham, MA USA.
   Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA.
   Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
   Royal N Shore Hosp, Div Cardiol, Sydney, NSW, Australia.
RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 330 Brookline Ave,Libby-303, Boston, MA 02215 USA.
FU NHLBI NIH HHS [R01-HL-48157]; NIAAA NIH HHS [K23-AA00299]
NR 49
TC 126
Z9 136
U1 0
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 SEP 18
PY 2001
VL 104
IS 12
BP 1367
EP 1373
DI 10.1161/hc3701.096067
PG 7
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 474XB
UT WOS:000171131200009
PM 11560851
ER

PT J
AU del Monte, F
   Williams, E
   Lebeche, D
   Schmidt, U
   Rosenzweig, A
   Gwathmey, JK
   Lewandowski, ED
   Hajjar, RJ
AF del Monte, F
   Williams, E
   Lebeche, D
   Schmidt, U
   Rosenzweig, A
   Gwathmey, JK
   Lewandowski, ED
   Hajjar, RJ
TI Improvement in survival and cardiac metabolism after gene transfer of
   sarcoplasmic reticulum Ca2+-ATPase in a rat model of heart failure
SO CIRCULATION
LA English
DT Article
DE gene therapy; heart failure; calcium; excitation; contractility
ID FAILING HUMAN MYOCARDIUM; DILATED CARDIOMYOPATHY; VENTRICULAR-FUNCTION;
   PROTEIN-LEVELS; PHOSPHOLAMBAN; PHOSPHORYLATION; SERCA2A; THERAPY
AB Background-In heart failure, sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling and contractile dysfunction. We have previously shown that increasing SERCA2a expression by gene transfer improves ventricular function in a rat model of heart failure created by ascending aortic constriction.
   Methods and Results-In this study, we tested the effects of gene transfer of SERCA2a on survival, left ventricular (LV) volumes, and metabolism. By 26 to 27 weeks after aortic banding, all animals developed heart failure (as documented by > 25% decrease in fractional shortening) and were randomized to receive either an adenovirus carrying the SERCA2a gene (Ad.SERCA2a) or control virus (Ad.beta gal-GFP) by use of a catheter-based technique. Sham-operated rats, uninfected or infected with either Ad.beta gal-GFP or Ad.SERCA2a, served as controls. Four weeks after gene transfer, survival in rats with heart failure treated with Ad.beta gal-GFP was 9%, compared with 63% in rats receiving Ad.SERCA2a. LV volumes were significantly increased in heart failure (0.64 +/-0.05 versus 0.35 +/-0.03 mL, P <0.02). Overexpression of SERCA2a normalized LV volumes (0.46 +/-0.07 mL) in the failing hearts. P-31 NMR analysis showed a reduced ratio of phosphocreatine to ATP content in failing+ Ad.beta gal-GFP compared with sham+Ad.beta gal-GFP (0.82 +/-0.13 versus 1.38 +/-0.14, P <0.01). Overexpression of SERCA2a in failing hearts improved the phosphocreatine/ ATP ratio (1.23 +/-0.28).
   Conclusions-In this study, we show that unlike inotropic agents that improve contractile function at the expense of increased mortality and worsening metabolism, gene transfer of SERCA2a improves survival and the energy potential in failing hearts.
C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
   Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Univ Illinois, Coll Med, Dept Physiol & Biophys, Chicago, IL 60680 USA.
RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,CNY-4, Charlestown, MA 02129 USA.
FU NHLBI NIH HHS [R01 HL049574-06S1, HL-49574, HL-50361, HL-57623,
   HL-59521, HL-61557, HL-62702, R01 HL049574-05, R01 HL049574-05S1, R01
   HL049574-06, R01 HL049574-07, R01 HL049574-08, R01 HL059521, R01
   HL061557, R01 HL062702]
NR 22
TC 231
Z9 236
U1 1
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-7322
J9 CIRCULATION
JI Circulation
PD SEP 18
PY 2001
VL 104
IS 12
BP 1424
EP 1429
DI 10.1161/hc3601.095574
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 474XB
UT WOS:000171131200018
PM 11560860
ER

PT J
AU Sun, T
   Echelard, Y
   Lu, R
   Yuk, DI
   Kaing, S
   Stiles, CD
   Rowitch, DH
AF Sun, T
   Echelard, Y
   Lu, R
   Yuk, DI
   Kaing, S
   Stiles, CD
   Rowitch, DH
TI Olig bHLH proteins interact with homeodomain proteins to regulate cell
   fate acquisition in progenitors of the ventral neural tube
SO CURRENT BIOLOGY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; HELIX TRANSCRIPTION FACTORS; SPINAL-CORD;
   EXPRESSION PATTERNS; DEVELOPING CNS; NEURONAL FATE; FAMILY; GENES;
   IDENTITY; IDENTIFICATION
AB Background: Organizing signals such as Sonic hedgehog are thought to specify neuronal subtype identity by regulating the expression of homeodomain proteins in progenitors of the embryonic neural tube. One of these, Nkx2.2, is necessary and sufficient for the development of V3 interneurons.
   Results: We report that Olig genes, encoding basic helix-loop-helix (bHLH) proteins, are expressed in a subset of Nkx2.2 progenitors before the establishment of interneurons and oligodendroglial precursors. Gain-of-function analysis in transgenic mouse embryos indicates that Olig genes specifically inhibit the establishment of Sim1-expressing V3 interneurons. Moreover, coexpression of Olig2 with Nkx2.2 in the chick neural tube generated cells expressing Sox10, a marker of oligodendroglial precursors. Colocalization of Olig and Nkx2.2 proteins at the dorsal extent of the Nkx2.2 expression domain is consistent with regulatory interactions that define the potential of progenitor cells in the border region.
   Conclusions: Interactions between homeodomain and Olig bHLH proteins evidently regulate neural cell fate acquisition and diversification in the ventral neural tube. In particular, interactions between Olig and Nkx2.2 proteins inhibit V3 interneuron development and promote the formation of alternate cell types, including those expressing Sox10.
C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   Genzyme Transgen Corp, Framingham, MA 01702 USA.
   Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA.
RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
FU NINDS NIH HHS [NS4051]
NR 33
TC 99
Z9 103
U1 0
U2 1
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD SEP 18
PY 2001
VL 11
IS 18
BP 1413
EP 1420
DI 10.1016/S0960-9822(01)00441-9
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 473VY
UT WOS:000171070500016
PM 11566099
ER

PT J
AU Walker, AK
   Rothman, JH
   Shi, Y
   Blackwell, TK
AF Walker, AK
   Rothman, JH
   Shi, Y
   Blackwell, TK
TI Distinct requirements for C-elegans TAF(II)s in early embryonic
   transcription
SO EMBO JOURNAL
LA English
DT Article
DE C. elegans; gene regulation; TAF(II)s; TFIID; transcription
ID RNA-POLYMERASE-II; CELL-CYCLE PROGRESSION; HISTONE-LIKE TAFS; TBP-LIKE
   FACTOR; CAENORHABDITIS-ELEGANS; IN-VIVO; TAF(II)-CONTAINING COMPLEX;
   DROSOPHILA-MELANOGASTER; ACETYLASE COMPLEX; GENE-EXPRESSION
AB TAF(II)s are conserved components of the TFIID, TFTC and SAGA-related mRNA transcription complexes. In yeast (y), yTAF(II)17 is required broadly for transcription, but various other TAF(II)s appear to have more specialized functions. It is important to determine how TAF(II)s contribute to transcription in metazoans, which have larger and more diverse genomes. We have examined TAF(II) functions in early Caenorhabditis elegans embryos, which can survive without transcription for several cell generations. We show that taf-10 (yTAF(II)7) and taf-11 (yTAF(II)25) are required for a significant fraction of transcription, but apparently are not needed for expression of multiple developmental and other metazoan-specific genes. In contrast, taf-5 (yTAF(II)48; human TAF(II)130) seems to be required for essentially all early embryonic mRNA transcription. We conclude that TAF-10 and TAF-11 have modular functions in metazoans, and can be bypassed at many metazoan-specific genes. The broad involvement of TAF-5 in mRNA transcription in vivo suggests a requirement for either TFIID or a TFTC-like complex.
C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA.
   Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA.
RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA.
FU NICHD NIH HHS [R01 HD037487, HD37487]; NIDDK NIH HHS [F32 DK0946]; NIGMS
   NIH HHS [R01 GM58012, R01 GM058012]
NR 72
TC 36
Z9 70
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0261-4189
J9 EMBO J
JI Embo J.
PD SEP 17
PY 2001
VL 20
IS 18
BP 5269
EP 5279
DI 10.1093/emboj/20.18.5269
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 477LN
UT WOS:000171285200023
PM 11566890
ER

PT J
AU Asahi, M
   Sumii, T
   Fini, ME
   Itohara, S
   Lo, EH
AF Asahi, M
   Sumii, T
   Fini, ME
   Itohara, S
   Lo, EH
TI Matrix metalloproteinase 2 gene knockout has no effect on acute brain
   injury after focal ischemia
SO NEUROREPORT
LA English
DT Article
DE extracellular matrix; mouse; neuroprotection; reperfusion injury;
   proteolysis; stroke
ID CEREBRAL-ISCHEMIA; MATRIX-METALLOPROTEINASE-9; INHIBITION; EXPRESSION;
   RAT; REPERFUSION; GELATINASE; HEMORRHAGE; INCREASE; MMP-2
AB Matrix metalloproteinases (MMPs) may contribute to tissue damage after cerebral ischemia. In this study, wildtype and MMP-2 knockout mice were subjected to permanent and transient (2 h) occlusions of the middle cerebral artery. Gelatin zymography showed that MMP-9 levels were increased in all brains after ischemia. MMP-2 levels did not show a significant increase in wildtype mice, and were not detectable in knockout mice. Laser doppler flowmetry demonstrated equivalent ischemic reductions in pet-fusion in wildtype and knockout mice. In both permanent and transient occlusion paradigms, there were no statistically significant differences between wildtype and knockout mice in terms of 24 h ischemic lesion volumes. These data suggest that MMP-2 does not contribute to acute tissue damage in this model of focal ischemia. NeuroReport 12:3003-3007 (C) 2001 Lippincott Williams & Wilkins.
C1 Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
   Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA.
   Tufts Univ, New England Eye Ctr, Vis Res Labs, Medford, MA 02155 USA.
   RIKEN, Brain Sci Inst, Lab Behav Genet, Wako, Saitama, Japan.
RP Lo, EH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, MGH E 149-2322, Charlestown, MA 02129 USA.
RI Itohara, Shigeyoshi/I-8769-2012
OI Itohara, Shigeyoshi/0000-0002-2410-9989
FU NEI NIH HHS [R01-EY12651]; NINDS NIH HHS [R01-NS40529, R01-NS37074,
   R01-NS38731]
NR 22
TC 120
Z9 131
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-4965
J9 NEUROREPORT
JI Neuroreport
PD SEP 17
PY 2001
VL 12
IS 13
BP 3003
EP 3007
DI 10.1097/00001756-200109170-00050
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 475JX
UT WOS:000171161700045
PM 11588620
ER

PT J
AU Mukherjee, S
AF Mukherjee, S
TI Heal thyself
SO NEW REPUBLIC
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Mukherjee, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NEW REPUBLIC INC
PI WASHINGTON
PA 1220 19TH ST NW SUITE 600, WASHINGTON, DC 20036 USA
SN 0028-6583
J9 NEW REPUBLIC
JI New Repub.
PD SEP 17
PY 2001
VL 225
IS 12
BP 57
EP 57
PG 1
WC Political Science
SC Government & Law
GA 471EA
UT WOS:000170913600017
ER

PT J
AU Sanchez, PL
   Harrell, LC
   Salas, RE
   Palacios, IF
AF Sanchez, PL
   Harrell, LC
   Salas, RE
   Palacios, IF
TI Learning curve of the Inoue technique of percutaneous mitral balloon
   valvuloplasty
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID FOLLOW-UP; VALVOTOMY; COMMISSUROTOMY; IMMEDIATE; REGURGITATION; CATHETER
AB There is controversy as to whether the double-balloon or the Inoue technique of percutaneous mitral balloon valvuloplasty (PMBV) provides superior immediate and long-term results. This study was undertaken to analyze the effect of the learning curve of the Inoue technique of PMBV in the immediate and long-term outcome of PMBV. The learning curve of Inoue PMBV was analyzed in 233 Inoue PMBVs divided into 2 groups: "early experience" (n = 100) and "late experience" (n = 133). The results of the overall Inoue technique were compared with those of 659 PMBVs performed with the double-balloon technique. Baseline clinical and morphologic characteristics between early and late experience Inoue groups were similar. Post-PMBV mitral valve area (1.89 +/- 0.56 vs 1.69 +/- 0.57 cm(2); p = 0.008) and success rate (60% vs 75.9%; p = 0.009) were significantly higher in the late experience Inoue group. Furthermore, there was a trend for less incidence of severe post-PMBV mitral regurgitation greater than or equal to3+ in the late experience group (6.8% vs 12%; p = 0.16). Although the post-PMBV mitral valve area was larger with the double-balloon technique (1.94 +/- 0.72 vs 1.81 +/- 0.58 cm(2); p = 0.01), the success rate (71.3% vs 69.1%; p = NS), incidence of greater than or equal to3+ mitral regurgitation (9% vs 9%), in-hospital complications, and long-term and event-free survival were similar with both techniques. In conclusion, there is a significant learning curve of the Inoue technique of PMBV. Both the Inoue and the double-balloon techniques are equally effective techniques of PMBV because they resulted in similar immediate success, in-hospital adverse events, and long-term and event-free survival. (C) 2001 by Excerpta Medica, Inc.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Cardiac Catherizat Lab,Cardiac Unit, Boston, MA 02114 USA.
RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Cardiac Catherizat Lab,Cardiac Unit, Bullfinch 105,55 Fruit St, Boston, MA 02114 USA.
OI Sanchez, Pedro L/0000-0002-4288-345X
NR 20
TC 15
Z9 16
U1 0
U2 0
PU EXCERPTA MEDICA INC
PI NEW YORK
PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD SEP 15
PY 2001
VL 88
IS 6
BP 662
EP 667
DI 10.1016/S0002-9149(01)01810-0
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 471KA
UT WOS:000170927500012
PM 11564391
ER

PT J
AU Januzzi, JL
   Sabatine, MS
   Choi, JC
   Abernethy, WB
   Isselbacher, EM
AF Januzzi, JL
   Sabatine, MS
   Choi, JC
   Abernethy, WB
   Isselbacher, EM
TI Refractory systemic hypertension following type B aortic dissection
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID MANAGEMENT
C1 Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Thorac Aort Ctr, 15 Parkman St,WAC-469, Boston, MA 02114 USA.
NR 15
TC 11
Z9 14
U1 0
U2 0
PU EXCERPTA MEDICA INC
PI NEW YORK
PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD SEP 15
PY 2001
VL 88
IS 6
BP 686
EP 688
DI 10.1016/S0002-9149(01)01818-5
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 471KA
UT WOS:000170927500020
PM 11564399
ER

PT J
AU Stone, WS
   Faraone, SV
   Seidman, LJ
   Green, AI
   Wojcik, JD
   Tsuang, MT
AF Stone, WS
   Faraone, SV
   Seidman, LJ
   Green, AI
   Wojcik, JD
   Tsuang, MT
TI Concurrent validation of schizotaxia: A pilot study
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE schizotaxia; negative symptoms; neuropsychological deficits;
   schizophrenia
ID SCHIZOPHRENIC-PATIENTS; NONPSYCHOTIC RELATIVES; DIAGNOSTIC INTERVIEW;
   HIPPOCAMPAL VOLUME; EYE-TRACKING; ATTENTION; COMORBIDITY; DISORDERS;
   SIBLINGS; ACCURACY
AB Background: Many first-degree relatives of patients with schizophrenia show deficits in clinical, neuropsychological, neurobiological and social domains, in the absence of psychosis. We recently reformulated Meehl's concept of schizotaxia to conceptualize the liability to schizophrenia, and we proposed preliminary criteria based on the presence of negative symptoms and neuropsychological deficits. Here we investigate the concurrent validity of schizotaxia by comparing a group of subjects who met criteria for schizotaxia with a group who did not on independent measures of clinical function, and on lifetime rates of selected comorbid psychiatric disorders.
   Methods: Twenty-seven adults who were first-degree, biological relatives of patients with schizophrenia were evaluated for schizotaxia based on our predetermined criteria involving negative symptoms and neuropsychological deficits. Subjects also received portions of the Diagnostic Interview for Genetic Studies, the Structured Interview for Schizotypy, the Family Interview for Genetic Studies, the DSM-IV Global Assessment of Functioning, the Physical Anhedonia Scale, the Social Adjustment Scale and the Symptom Checklist-90-Revised. Subjects who met criteria for schizotaxia were compared with those who did not on each of the clinical measures, and on their rates of comorbid DSM-IV psychiatric diagnoses.
   Results: Eight subjects met criteria for schizotaxia, and 19 did not. Subjects with schizotaxia showed significantly lower levels of function on each of the clinical scales. Differences in comorbid psychiatric diagnoses were not significant, although the rate of lifetime substance abuse diagnoses in the schizotaxic group (50%) approached levels that are often seen in schizophrenia.
   Conclusions: These findings provide the first evidence of concurrent validation for a proposed syndrome of schizotaxia. They, are also consistent with the view that the vulnerability to schizophrenia may be defined, at least partially, although larger studies to assess both the concurrent and predictive validity schizotaxia will be required to confirm these results. Biol Psychiatry 2001; 50:434-440 (C) 2001 Society of Biological Psychiatry.
C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA.
   Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Brockton W Roxbury Vet Affairs Med Ctr, Dept Psychiat, Boston, MA USA.
   Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA.
   Massachusetts Mental Hlth Ctr, Commonwealth Res Ctr, Boston, MA 02115 USA.
RP Stone, WS (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA.
OI Faraone, Stephen/0000-0002-9217-3982
FU NIMH NIH HHS [1R01 MH41879-01, 1R37 MH43518-01, 1RO1 MH49891, 1RO1
   MH52386, 5U01 MH46318-02]
NR 40
TC 22
Z9 25
U1 3
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 0006-3223
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD SEP 15
PY 2001
VL 50
IS 6
BP 434
EP 440
DI 10.1016/S0006-3223(01)01116-7
PG 7
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 473GL
UT WOS:000171032100005
PM 11566160
ER

PT J
AU Lieberman, J
   Shankar, P
   Manjunath, N
   Andersson, J
AF Lieberman, J
   Shankar, P
   Manjunath, N
   Andersson, J
TI Dressed to kill? A review of why antiviral CD8 T lymphocytes fail to
   prevent progressive immunodeficiency in HIV-1 infection
SO BLOOD
LA English
DT Review
ID RECEPTOR ZETA-CHAIN; BLOOD DENDRITIC CELLS; CLASS-I MOLECULES;
   VIRUS-INFECTION; INHIBITORY RECEPTORS; PERIPHERAL-BLOOD;
   IMMUNE-RESPONSES; IFN-GAMMA; SEROPOSITIVE INDIVIDUALS; DISEASE
   PROGRESSION
AB CD8 T cells play an important role in protection and control of HIV-1 by direct cytolysis of infected cells and by suppression of viral replication by secreted factors. However, although HIV-1-infected individuals have a high frequency of HIV-1-specific CD8 T cells, viral reservoirs persist and progressive immunodeficiency generally ensues in the absence of continuous potent antiviral drugs. Freshly isolated HIV-specific CD8 T cells are often unable to lyse HIV-1-infected cells. Maturation into competent cytotoxic T lymphocytes may be blocked during the initial encounter with antigen because of defects in antigen presentation by interdigitating dendritic cells or HIV-Infected macrophages. The molecular basis for impaired function is multifactorial, due to incomplete T-cell signaling and activation (in part related to CD3 zeta and CD28 down-modulation), reduced perforin expression, and inefficient trafficking of HIV-specific CD8 T cells to lymphoid sites of infection. CD8 T-cell dysfunction can partially be corrected in vitro with short-term exposure to interleukin 2, suggesting that impaired HIV-specific CD4 T helper function may play a significant causal or exacerbating role. Functional defects are qualitatively different and more severe with advanced disease, when interferon gamma production also becomes compromised. (C) 2001 by The American Society of Hematology.
C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   Huddinge Univ Hosp, Karolinska Inst, Ctr Infect Med, Div Infect Dis, Stockholm, Sweden.
RP Lieberman, J (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA.
RI Lieberman, Judy/A-2717-2015
FU NIAID NIH HHS [AI-41536, AI-42519, AI-45406]
NR 180
TC 188
Z9 193
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 15
PY 2001
VL 98
IS 6
BP 1667
EP 1677
DI 10.1182/blood.V98.6.1667
PG 11
WC Hematology
SC Hematology
GA 471UV
UT WOS:000170947800008
PM 11535496
ER

PT J
AU Migone, TS
   Humbert, M
   Rascle, A
   Sanden, D
   D'Andrea, A
   Johnston, JA
AF Migone, TS
   Humbert, M
   Rascle, A
   Sanden, D
   D'Andrea, A
   Johnston, JA
TI The deubiquitinating enzyme DUB-2 prolongs cytokine-induced signal
   transducers and activators of transcription activation and suppresses
   apoptosis following cytokine withdrawal
SO BLOOD
LA English
DT Article
ID JAK-STAT PATHWAY; T-CELL LEUKEMIA; CONSTITUTIVE ACTIVATION; JAK/STAT
   PATHWAY; TRANSGENIC MICE; ABL ONCOGENE; C-MYC; PROLIFERATION; RECEPTOR;
   PROTEINS
AB Cytokines, such as interleukin-2 (IL-2), activate intracellular signaling pathways via rapid tyrosine phosphorylation of their receptors, resulting in the activation of many genes involved in cell growth and survival. The deubiquitinating enzyme DUB-2 is induced in response to IL-2 but as yet its function has not been determined. The results of this study show that DUB-2 is expressed in human T-cell lymphotropic virus-I(HTLV-1)-transformed T cells that exhibit constitutive activation of the IL-2 JAK/STAT (signal transducers and activators of transcription) pathway, and when expressed in Ba/F3 cells DUB-2 markedly prolonged IL-2-induced STAT5 phosphorylation. Although DUB-2 did not enhance IL-2-mediated proliferation, when withdrawn from growth factor, cells expressing DUB-2 had sustained STAT5 phosphorylation and enhanced expression of IL-2-induced genes cis and c-myc. Moreover, DUB-2 expression markedly inhibited apoptosis induced by cytokine withdrawal allowing cells to survive. Taken together these data suggest that DUB-2 can enhance signaling through the JAK/STAT pathway, prolong lymphocyte survival, and, when constitutively expressed, may contribute to the activation of the JAK/STAT pathway observed in some transformed cells.
C1 DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA USA.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol & Cellular & Mol Biol, Boston, MA 02115 USA.
RP Johnston, JA (reprint author), Queens Univ Belfast, Dept Immunol, Whitia Med Bldg,97 Lisburn Rd, Belfast BT9 7BL, Antrim, North Ireland.
NR 40
TC 36
Z9 38
U1 0
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 15
PY 2001
VL 98
IS 6
BP 1935
EP 1941
DI 10.1182/blood.V98.6.1935
PG 7
WC Hematology
SC Hematology
GA 471UV
UT WOS:000170947800046
PM 11535532
ER

PT J
AU Zlatescu, MC
   TehraniYazdi, A
   Sasaki, H
   Megyesi, JF
   Betensky, RA
   Louis, DN
   Cairncross, JG
AF Zlatescu, MC
   TehraniYazdi, A
   Sasaki, H
   Megyesi, JF
   Betensky, RA
   Louis, DN
   Cairncross, JG
TI Tumor location and growth pattern correlate with genetic signature in
   oligodendroglial neoplasms
SO CANCER RESEARCH
LA English
DT Article
ID SUCCESSFUL CHEMOTHERAPY; PREDICTORS; SURVIVAL
AB Molecular genetic subsets of anaplastic oligodendroglioma behave in biologically distinct ways, in both their rates of growth and their responses to standard therapies. In a series of 64 cases, we evaluated whether allelic loss of chromosomal arms lp and 19q, an early molecular event in the genesis of chemosensitive oligodendrogliomas, is related to tumor location and extent of tumor spread in the brain. We observed that tumor genotype was closely associated with tumor location (P < 0.001). Anaplastic oligo dendrogliomas located in the frontal, parietal, and occipital lobes were significantly more likely to harbor allelic loss of chromosomal arms lp and 19q than histologically indistinguishable tumors arising in the temporal lobe, insula, and diencephalon (P < 0.001). In addition, loss of heterozygosity for lp and 19q was significantly associated with a bilateral pattern of growth (P = 0.037); all seven bilaterally distributed anaplastic oligodendrogliomas had lp and 19q allelic loss. We conclude, therefore, that molecular subtypes of oligodendrogliomas may arise preferentially in certain lobes of the brain and have differential patterns of growth, with tumors having allelic loss of chromosomes lp and 19q occurring most frequently in the frontal lobes and having a tendency for widespread growth across the midline. These findings encourage inquiries into the biological basis of such marked differences and already have implications for the current management of these neoplasms.
C1 London Reg Canc Ctr, London, ON N6A 4L6, Canada.
   Univ Western Ontario, Dept Oncol, London, ON N6A 4L6, Canada.
   Univ Western Ontario, Dept Clin Neurol Sci, London, ON N6A 4L6, Canada.
   Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA.
RP Cairncross, JG (reprint author), London Reg Canc Ctr, 790 Commissioners Rd E, London, ON N6A 4L6, Canada.
FU NCI NIH HHS [CA57683]
NR 12
TC 145
Z9 150
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 SEP 15
PY 2001
VL 61
IS 18
BP 6713
EP 6715
PG 3
WC Oncology
SC Oncology
GA 474LK
UT WOS:000171108400019
PM 11559541
ER

PT J
AU Mylonakis, E
   Koutkia, P
   Grinspoon, S
AF Mylonakis, E
   Koutkia, P
   Grinspoon, S
TI Diagnosis and treatment of androgen deficiency in human immunodeficiency
   virus-infected men and women
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID HIV-INFECTION; WEIGHT-LOSS; TESTOSTERONE REPLACEMENT; TESTICULAR
   ATROPHY; CONTROLLED TRIAL; HYPOGONADAL MEN; POSITIVE MEN; THERAPY;
   ENDOCRINE; SYSTEM
AB Androgen deficiency is a common endocrine abnormality among men and women with human immunodeficiency virus (HIV) infection. Low testosterone concentrations are associated with lower CD4 cell count, advanced stage of illness, medication use, and weight loss. Signs and symptoms may be nonspecific. The most useful laboratory indicator is the serum bioavailable (free) testosterone concentration. A number of different testosterone preparations for treatment of androgen deficiency in HIV-infected men now exist. Administration of im testosterone significantly increases weight and lean body mass, energy, quality of life, and depression scores in HIV-infected men with low testosterone levels. Newer transdermal and gel preparations provide more-consistent steady-state dosing but are not as well tested, and sufficient testosterone concentrations may not be achieved with their use. Androgen deficiency is also common among HIV-infected women. Preliminary studies suggest that use of physiological testosterone administration, to achieve testosterone levels within the normal range, is of benefit in HIV-infected women, but further studies are necessary to define the therapeutic role of androgen therapy in this population.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA.
   Boston Univ, Med Ctr, Dept Diabet Endocrinol & Metab, Boston, MA USA.
RP Grinspoon, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA.
NR 38
TC 35
Z9 35
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP 15
PY 2001
VL 33
IS 6
BP 857
EP 864
DI 10.1086/322695
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 472PZ
UT WOS:000170994700020
PM 11512091
ER

PT J
AU Stone, VE
AF Stone, VE
TI Strategies for optimizing adherence to highly active antiretroviral
   therapy: Lessons from research and clinical practice
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID PROTEASE INHIBITOR THERAPY; VIROLOGICAL FAILURE; REPORTED ADHERENCE;
   PATIENT COMPLIANCE; DRUG-RESISTANCE; HIV-INFECTION; VIRAL LOAD;
   REGIMENS; HIV/AIDS; INTERVENTIONS
AB Successful treatment of human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) with highly active antiretroviral therapy (HAART) requires that patients maintain nearly perfect adherence to the prescribed regimen. Suboptimal adherence to antiretroviral therapy is clearly the most common cause of virologic failure of HAART regimens. Given the critical role of adherence in successful antiretroviral therapy, it is essential that providers of care for patients with HIV infection have a strategy that proactively assists and supports their patients' efforts to adhere to medication regimens. This review endeavors to provide a clinically focused approach to optimizing adherence of patients to HAART.
C1 Brown Univ, Sch Med, Mem Hosp Rhode Isl, Dept Med, Providence, RI 02912 USA.
RP Stone, VE (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
NR 47
TC 132
Z9 139
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP 15
PY 2001
VL 33
IS 6
BP 865
EP 872
DI 10.1086/322698
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 472PZ
UT WOS:000170994700021
PM 11512092
ER

PT J
AU Craig, WA
AF Craig, WA
TI Does the dose matter?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT Meeting of the American-Academy-of-Arts-and-Sciences
CY DEC, 1999
CL CAMBRIDGE, MA
SP Amer Acad Arts Sci
ID RESPIRATORY-TRACT INFECTIONS; ACUTE OTITIS-MEDIA;
   STREPTOCOCCUS-PNEUMONIAE; INTRAVENOUS CIPROFLOXACIN;
   AMOXICILLIN-CLAVULANATE; STAPHYLOCOCCUS-AUREUS; ILL-PATIENTS; IN-VIVO;
   PHARMACODYNAMICS; MODEL
AB Pharmacokinetic/pharmacodynamic (PK/PD) parameters, such as the ratio of peak to minimum inhibitory concentration (peak/MIC ratio), ratio of 24-hour area under the curve to MIC (24-h AUC/MIC ratio), and the time above MIC, are good indicators of the drug dose-organism interaction. Time above the MIC is the important determinant of the activity of beta -lactams, macrolides, clindamycin, and linezolid. Free drug serum levels of these drugs should be above the MIC for at least 40%-50% of the dosing interval to produce adequate clinical and microbiological efficacy. Peak/MIC and 24-h AUC/MIC ratios are major determinants of the activity of aminoglycosides and fluoroquinolones. In general, peak/MIC ratios should exceed 8 and 24-h AUC/MIC values should be >100 to successfully treat gram-negative bacillary infections and to prevent the emergence of resistant organisms during therapy. The successful treatment of pneumococcal infections with fluoroquinolones and azithromycin appear to require 24-h AUC/MIC ratios of only 25-35. Mutation prevention concentrations are being reported for various fluoroquinolones with different pathogens, but their clinical significance has not yet been established. More information is needed on the role of PK/PD parameters and their magnitude for preventing mutations and the emergence of resistant organisms for most classes of antibiotics.
C1 Univ Wisconsin, Dept Med, Madison, WI USA.
RP Craig, WA (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA.
EM wac@medicine.wisc.edu
NR 30
TC 111
Z9 113
U1 1
U2 5
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 SEP 15
PY 2001
VL 33
SU 3
BP S233
EP S237
DI 10.1086/321854
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 473TG
UT WOS:000171063700022
PM 11524724
ER

PT J
AU Ferraro, MJ
AF Ferraro, MJ
TI Should we reevaluate antibiotic breakpoints?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT Meeting of the American-Academy-of-Arts-and-Sciences
CY DEC, 1999
CL CAMBRIDGE, MASSACHUSETTS
SP Amer Acad Arts Sci
AB The breakpoints used to interpret antimicrobial susceptibility tests should be carefully determined initially, using microbiological, pharmacokinetic, pharmacodynamic, and clinical data, and then reevaluated periodically as changes in bacterial resistance, susceptibility test methods, or antibiotic formulations occur. Throughout the world, different governmental agencies and professional organizations have responsibility for the initial establishment of antibiotic susceptibility breakpoints. In the United States, the National Committee for Clinical Laboratory Standards has a mechanism in place to establish breakpoints initially and to review and publish updates on an annual basis. There should be a continued effort to coordinate both susceptibility testing methods and breakpoint determinations in various parts of the world.
C1 Massachusetts Gen Hosp, Clin Microbiol Lab, GRB 526, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Ferraro, MJ (reprint author), Massachusetts Gen Hosp, Clin Microbiol Lab, GRB 526, Boston, MA 02114 USA.
NR 4
TC 16
Z9 17
U1 0
U2 0
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP 15
PY 2001
VL 33
SU 3
BP S227
EP S229
DI 10.1086/321852
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 473TG
UT WOS:000171063700020
PM 11524723
ER

PT J
AU Hooper, DC
AF Hooper, DC
TI Minimizing potential resistance: The molecular view - A comment on
   Courvalin and Trieu-Cuot
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT Meeting of the American-Academy-of-Arts-and-Sciences
CY DEC, 1999
CL CAMBRIDGE, MASSACHUSETTS
SP Amer Acad Arts Sci
ID MULTIDRUG EFFLUX SYSTEMS; STAPHYLOCOCCUS-AUREUS;
   STREPTOCOCCUS-PNEUMONIAE; ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI;
   METHICILLIN RESISTANCE; PSEUDOMONAS-AERUGINOSA; BINDING PROTEINS;
   TOPOISOMERASE-IV; DNA GYRASE
AB The complexity of bacterial resistance to antimicrobial agents is driven by the interplay of many mechanistic and epidemiologic factors. Mechanistically, resistance by target alteration, reduced permeation, and drug inactivation can occur by both chromosomal mutation and acquisition of new genetic elements. Epidemiologically, exposure to antimicrobial agents provides a growth or persistence advantage for any existing resistant bacteria, generally irrespective of the mechanism. When a single chromosomal mutation is sufficient to cause resistance, any such exposure provides a risk of selection, as long as a sufficiently large bacterial population is exposed. Transmission of resistant bacteria can also amplify resistance of any type, but it is particularly important for complex resistance mechanisms that have evolved over time and for mechanisms that depend on infrequent biological events in nature. Because true biological barriers to the development of resistance are likely to be elusive, multiple approaches that address both the use of antimicrobial agents and transmission are necessary to slow the advance of resistance.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA.
RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA.
NR 29
TC 9
Z9 9
U1 0
U2 2
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP 15
PY 2001
VL 33
SU 3
BP S157
EP S160
DI 10.1086/321842
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 473TG
UT WOS:000171063700010
PM 11524713
ER

PT J
AU Goldfine, AB
AF Goldfine, AB
TI Type 2 diabetes: New drugs, new perspectives
SO HOSPITAL PRACTICE
LA English
DT Article
AB Detection at younger ages is rapidly increasing. Although diet and exercise remain the mainstays of therapy, physicians can now choose from among a variety of medications targeting different pathophysiologic facets of the disease. The newest drugs are the thiazolidinediones, a totally novel class of insulin sensitizers.
C1 Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Goldfine, AB (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA.
NR 6
TC 2
Z9 2
U1 0
U2 0
PU MCGRAW HILL HEALTHCARE PUBLICATIONS
PI MINNEAPOLIS
PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA
SN 8750-2836
J9 HOSP PRACT
JI Hosp. Pract.
PD SEP 15
PY 2001
VL 36
IS 9
BP 29
EP 36
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 472WB
UT WOS:000171007000004
PM 11565740
ER

PT J
AU Muratoglu, OK
   Harris, WH
AF Muratoglu, OK
   Harris, WH
TI Identification and quantification of irradiation in UHMWPE through
   trans-vinylene yield
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
LA English
DT Article
DE UHMWPE; crosslinking; trans-vinylene unsaturation; radiation dose; gamma
   and e-beam irradiation
ID MOLECULAR-WEIGHT POLYETHYLENE; MODEL
AB trans-Vinylene unsaturations generated in ultrahigh-molecular-weight polyethylene (UHMWPE) after radiation treatment scales linearly with the absorbed dose level, and can serve as an internal dosimeter for determining the radiation dose level for sterilizing or crosslinking UHMWPE. We measured the trans-vinylene concentration using infrared spectroscopy and generated calibration curves for ultrahigh-molecular-weight polyethylene (ram-extruded GUR 1050) after cold e-beam, cold gamma, and warm e-beam irradiations. The trans-vinylene content increased linearly with the absorbed dose level in all cases except with cold gamma irradiation at dose levels higher than similar to 70 kGy. At that dose level the trans-vinylene content of the warm irradiated samples was higher than those of the cold irradiated samples. Following postirradiation melting, the trans-vinylene content of the gamma irradiated samples increased. Such trans-vinylene quantification can be an internal dosimeter for crosslinked UHMWPE when radiation is used for improving its wear resistance or sterilizing the device made thereof. It can also be utilized to assess the spatial uniformity of the absorbed radiation dose level. (C) 2001 John Wiley & Sons, Inc.
C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA.
RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA.
NR 22
TC 30
Z9 31
U1 0
U2 5
PU JOHN WILEY & SONS INC
PI NEW YORK
PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0021-9304
J9 J BIOMED MATER RES
JI J. Biomed. Mater. Res.
PD SEP 15
PY 2001
VL 56
IS 4
BP 584
EP 592
DI 10.1002/1097-4636(20010915)56:4<584::AID-JBM1131>3.0.CO;2-Y
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 447EZ
UT WOS:000169559500015
PM 11400137
ER

PT J
AU Goldhirsch, A
   Glick, JH
   Gelber, RD
   Coates, AS
   Senn, HJ
AF Goldhirsch, A
   Glick, JH
   Gelber, RD
   Coates, AS
   Senn, HJ
TI Meeting highlights: International consensus panel on the treatment of
   primary breast cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID SURGICAL-ADJUVANT-BREAST; RANDOMIZED CONTROLLED TRIAL; BRCA2 MUTATION
   CARRIERS; HIGH-DOSE CHEMOTHERAPY; SENTINEL-NODE BIOPSY; CARCINOMA
   IN-SITU; QUALITY-OF-LIFE; HIGH-RISK; PROPHYLACTIC MASTECTOMY; SERUM
   ESTRADIOL
C1 Oncol Inst So Switzerland, Int Breast Canc Study Grp, Lugano, Switzerland.
   Zentrum Tumordiagnost & Pravent, St Gallen, Switzerland.
   European Inst Oncol, Int Breast Canc Study Grp, I-20141 Milan, Italy.
   Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA.
   Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA.
   Australian Canc Soc, E Sydney, Australia.
   Univ Sydney, E Sydney, Australia.
RP Goldhirsch, A (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Via Ripamonti 435, I-20141 Milan, Italy.
NR 83
TC 484
Z9 503
U1 1
U2 6
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 SEP 15
PY 2001
VL 19
IS 18
BP 3817
EP 3827
PG 11
WC Oncology
SC Oncology
GA 473KR
UT WOS:000171043400005
PM 11559719
ER

PT J
AU Soignet, SL
   Frankel, SR
   Douer, D
   Tallman, MS
   Kantarjian, H
   Calleja, E
   Stone, RM
   Kalaycio, M
   Scheinberg, DA
   Steinherz, P
   Sievers, EL
   Coutre, S
   Dahlberg, S
   Ellison, R
   Warrell, RP
AF Soignet, SL
   Frankel, SR
   Douer, D
   Tallman, MS
   Kantarjian, H
   Calleja, E
   Stone, RM
   Kalaycio, M
   Scheinberg, DA
   Steinherz, P
   Sievers, EL
   Coutre, S
   Dahlberg, S
   Ellison, R
   Warrell, RP
TI United States multicenter study of arsenic trioxide in relapsed acute
   promyelocytic leukemia
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article; Proceedings Paper
CT 42nd Annual Meeting of the American-Society-of-Hematology
CY DEC 01-05, 2000
CL SAN FRANCISCO, CALIFORNIA
SP Amer Soc Hematol
ID TRANS-RETINOIC ACID; PML-RAR-ALPHA; POLYMERASE CHAIN-REACTION; MINIMAL
   RESIDUAL DISEASE; CHEMOTHERAPY; EXPRESSION; THERAPY; TRANSLOCATION;
   LEUKOCYTOSIS; T(15-17)
AB Purpose: To determine the safety and efficacy of arsenic trioxide (ATO) in patients with relapsed acute promyelocytic leukemia (APL).
   Patients and Methods: Forty patients experiencing first (n = 21) or greater than or equal to second (n = 19) relapse were treated with daily infusions of ATO to a maximum of 60 doses or until all leukemic cells in bone marrow were eliminated. Patients who achieved a complete remission (CR) were offered one consolidation course of ATO that began 3 to 4 weeks later. Patients who remained in CR were eligible to receive further cycles of ATO therapy on a maintenance study.
   Results: Thirty-four patients (85%) achieved a CR. Thirty-one patients (91%) with CRs had posttreatment cytogenetic tests negative for t(15;17). Eighty-six percent of the patients who were assessable by reverse transcriptase polymerase chain reaction converted from positive to negative for the promyelocytic leukemia/retinoic acid receptor-alpha transcript by the completion of their consolidation therapy. Thirty-two patients received consolidation therapy, and 18 received additional ATO as maintenance. Eleven patients underwent allogeneic (n = 8) or autologous (n = 3) transplant after ATO treatment. The 18-month overall and relapse-free survival (RFS) estimates were 66% and 56%, respectively. Twenty patients (50%) had leukocytosis (> 10,000 WBC/muL) during induction therapy. Ten patients developed signs or symptoms suggestive of the APL syndrome and were effectively treated with dexamethasone. Electrocardiographic QT prolongation was common (63%). One patient had an absolute QT interval of > 500 msec and had an asymptomatic 7-beat run of torsades de pointe. Two patients died during induction, neither from drug-related causes.
   Conclusion: This study establishes ATO as a highly effective therapy for patients with relapsed APL. J Clin Oncol 19:3852-3860. (C) 2001 by American Society of Clinical Oncology.
C1 Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia & Dev Chemotherapy Serv, New York, NY 10021 USA.
   Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA.
   Cornell Univ, Joan & Sanford Weill Med Coll, New York, NY USA.
   Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA.
   Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
   Univ So Calif, Univ So Calif Keck Sch Med, Los Angeles, CA USA.
   Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
   Northwestern Univ, Sch Med, Chicago, IL USA.
   Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Cleveland Clin Fdn, Cleveland, OH 44195 USA.
   Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
   Cell Therapeut Inc, Seattle, WA USA.
RP Soignet, SL (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia & Dev Chemotherapy Serv, 1275 York Ave, New York, NY 10021 USA.
FU NCI NIH HHS [CA87441]
NR 26
TC 498
Z9 523
U1 2
U2 7
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 SEP 15
PY 2001
VL 19
IS 18
BP 3852
EP 3860
PG 9
WC Oncology
SC Oncology
GA 473KR
UT WOS:000171043400009
PM 11559723
ER

PT J
AU Das, A
   Asatryan, L
   Reddy, MA
   Wass, CA
   Stins, MF
   Joshi, S
   Bonventre, JV
   Kim, KS
AF Das, A
   Asatryan, L
   Reddy, MA
   Wass, CA
   Stins, MF
   Joshi, S
   Bonventre, JV
   Kim, KS
TI Differential role of cytosolic phospholipase A(2) in the invasion of
   brain microvascular endothelial cells by Escherichia coli and Listeria
   monocytogenes
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 39th Interdisciplinary Conference on Antimicrobial Agents and
   Chemotherapy (ICAAC)
CY SEP 26-29, 1999
CL SAN FRANCISCO, CALIFORNIA
ID CALCIUM-INDEPENDENT PHOSPHOLIPASE-A2; MEMBRANE PROTEIN-A; BISCOCLAURINE
   ALKALOIDS; BACTERIAL-MENINGITIS; INHIBITION; ACID; MACROPHAGE;
   ACTIVATION; EXPRESSION; PLATELETS
AB Invasion of brain microvascular endothelial cells (BMECs) is a key step in the pathogenesis of meningitis due to Escherichia coli and Listeria monocytogenes. Although host cell actin cytoskeletal rearrangements are essential in BMEC invasion by E. coli K1 and L. monocytogenes, the underlying signaling mechanisms remain unclear. This study demonstrates that host cell cytosolic phospholipase A(2) (cPLA(2)) contributes to E. coli K1 invasion of BMECs but not to L. monocytogenes invasion of BMECs. This difference was observed with 4-bromophenacyl bromide, a nonselective PLA(2) inhibitor, and arachidonyl trifluoromethyl ketone, a selective cPLA(2) inhibitor, and was confirmed with BMEC derived from cPLA(2) knockout mice. Activation of cPLA(2) leads to generation of intracellular arachidonic acid, which is metabolized via cyclooxygenase (COX) and lipo-oxygenase (LOX) pathways into eicosanoids. COX and LOX inhibitors also significantly inhibit E. coli K1 invasion of BMECs.
C1 Childrens Hosp Los Angeles, Div Infect Dis, Los Angeles, CA 90027 USA.
   Childrens Hosp Los Angeles, Div Hematol & Oncol, Los Angeles, CA 90027 USA.
   Massachusetts Gen Hosp, Dept Med, Charlestown, MA USA.
RP Das, A (reprint author), Childrens Hosp Los Angeles, Div Infect Dis, 4650 Sunset Blvd,Mail Stop 51, Los Angeles, CA 90027 USA.
FU NHLBI NIH HHS [HL-61951]; NIAID NIH HHS [AI-47225]; NINDS NIH HHS
   [NS-26310]
NR 36
TC 28
Z9 30
U1 0
U2 0
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 SEP 15
PY 2001
VL 184
IS 6
BP 732
EP 737
DI 10.1086/322986
PG 6
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 472PE
UT WOS:000170992000009
PM 11517434
ER

PT J
AU Fernandez, IM
   Silva, M
   Schuch, R
   Walker, WA
   Siber, AM
   Maurelli, AT
   McCormick, BA
AF Fernandez, IM
   Silva, M
   Schuch, R
   Walker, WA
   Siber, AM
   Maurelli, AT
   McCormick, BA
TI Cadaverine prevents the escape of Shigella flexneri from the
   phagolysosome: A connection between bacterial dissemination and
   neutrophil transepithelial signaling
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
ID POLYMORPHONUCLEAR LEUKOCYTE TRANSMIGRATION; INTESTINAL EPITHELIAL
   MONOLAYERS; INVASION PLASMID ANTIGENS; HELA-CELLS; CYTOSKELETAL
   REARRANGEMENTS; VIRULENCE PLASMID; ACTIN-FILAMENTS; FUNCTIONAL-ROLE; IPA
   INVASINS; F-ACTIN
AB Shigella flexneri causes bacillary dysentery in humans by invading epithelial cells of the colon, which is characterized by an acute polymorphonuclear leukocyte (PMNL)-rich inflammation. Our recent studies demonstrated that cadaverine, a polyamine, specifically acts to abrogate transepithelial signaling to PMNL induced by S. flexneri. Here, insight is provided into the cellular mechanisms by which cadaverine attenuates the ability of Shigella species to induce PMNL signaling. It was found that cadaverine retards the lysis of the Shigella species-containing vacuole, suggesting that a blockade is established, in which the pathogen is prevented from adequately interacting with the cytoskeleton. Furthermore, an IcsA mutant of S. flexneri that cannot interact with the cytoskeleton and spreads intercellularly fails to induce transmigration of PMNL. Results indicate that cadaverine-induced compartmentalization of Shigella species to the phagolysosome might be a protective response of the host that directly contributes to the diminished ability of PMNL to transmigrate across model intestinal epithelia.
C1 Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Labs, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA.
RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Labs, 114 16th St 114-3503, Charlestown, MA 02129 USA.
FU NIAID NIH HHS [AI-24656]; NICHD NIH HHS [HD-12437, HD-31852]; NIDDK NIH
   HHS [DK-50989, DK-33506]
NR 51
TC 32
Z9 32
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 SEP 15
PY 2001
VL 184
IS 6
BP 743
EP 753
DI 10.1086/323035
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 472PE
UT WOS:000170992000011
PM 11517436
ER

PT J
AU Giovannini, MG
   Blitzer, RD
   Wong, T
   Asoma, K
   Tsokas, P
   Morrison, JH
   Iyengar, R
   Landau, EM
AF Giovannini, MG
   Blitzer, RD
   Wong, T
   Asoma, K
   Tsokas, P
   Morrison, JH
   Iyengar, R
   Landau, EM
TI Mitogen-activated protein kinase regulates early phosphorylation and
   delayed expression of Ca2+/calmodulin-dependent protein kinase II in
   long-term potentiation
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE long-term potentiation; mitogen-activated protein kinase; Erk;
   Ca2+/calmodulin-dependent protein kinase II; beta-adrenergic receptors;
   rat hippocampus; phosphorylation; protein synthesis
ID CYTOSOLIC PHOSPHOLIPASE A(2); THETA-FREQUENCY STIMULATION;
   ELEMENT-BINDING PROTEIN; HIPPOCAMPAL CA1 NEURONS; EPIDERMAL
   GROWTH-FACTOR; D-ASPARTATE RECEPTOR; MESSENGER-RNA; IN-VIVO;
   PHOSPHATASE-ACTIVITY; SYNAPTIC PLASTICITY
AB Activation of mitogen-activated protein kinase (MAPK) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) are required for numerous forms of neuronal plasticity, including long-term potentiation (LTP). We induced LTP in rat hippocampal area CA1 using theta-pulse stimulation (TPS) paired with beta -adrenergic receptor activation [isoproterenol (ISO)], a protocol that may be particularly relevant to normal patterns of hippocampal activity during learning. This stimulation resulted in a transient phosphorylation of p42 MAPK, and the resulting LTP was MAPK dependent. In addition, CaMKII was regulated in two, temporally distinct ways after TPS-ISO: a transient rise in the fraction of phosphorylated CaMKII and a subsequent persistent increase in CaMKII expression. The increases in MAPK and CaMKII phosphorylation were strongly colocalized in the dendrites and cell bodies of CA1 pyramidal cells, and both the transient phosphorylation and delayed expression of CaMKII were prevented by inhibiting p42/p44 MAPK. These results establish a novel bimodal regulation of CaMKII by MAPK, which may contribute to both post-translational modification and increased gene expression.
C1 Mt Sinai Sch Med, Dept Pharmacol, New York, NY 10029 USA.
   Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA.
   Mt Sinai Sch Med, Neurobiol Aging Labs, New York, NY 10029 USA.
   Bronx Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY 10468 USA.
   Univ Florence, Dipartimento Farmacol Preclin & Clin, Florence, Italy.
RP Blitzer, RD (reprint author), Mt Sinai Sch Med, Dept Pharmacol, Box 1215,1 Gustave Levy Pl, New York, NY 10029 USA.
RI Morrison, John/F-9229-2012
FU NIA NIH HHS [AG06647]; NIGMS NIH HHS [GM5408]; NINDS NIH HHS [NS33646]
NR 76
TC 79
Z9 82
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 SEP 15
PY 2001
VL 21
IS 18
BP 7053
EP 7062
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 471HM
UT WOS:000170922800009
PM 11549715
ER

PT J
AU Wilhelmi, BJ
   Snyder, N
   Verbesey, JE
   Ganchi, PA
   Lee, WPA
AF Wilhelmi, BJ
   Snyder, N
   Verbesey, JE
   Ganchi, PA
   Lee, WPA
TI Trigger finger release with hand surface landmark ratios: An anatomic
   and clinical study
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article; Proceedings Paper
CT 69th Annual Meeting of the
   American-Society-of-Plastic-and-Reconstructive-Surgeons
CY OCT 14-18, 2000
CL LOS ANGELES, CALIFORNIA
SP Amer Soc Plast & Reconstruct Surgeons
AB The purpose of this study was to identify surface landmark ratios to locate the Al pulley and clarify the controversy of differing anatomic descriptions of the Al, CO, and A pulleys. Minimally invasive and percutaneous approaches to Al pulley release maybe facilitated with surface landmark ratios, which identify, and predict the proximal and distal margins of the Al pulley. Two-hundred fifty-sixty fingers were dissected in 64 preserved cadaver hands. Measurements of Al pulley lengths and pulley margins in relation to surface landmarks were obtained. Ve found that the distance from the palmar digital crease to the proximal interphalangeal crease (mean, 2.42 +/- 0.03 cin) corresponds to the distance of the proximal edge of the Al pulley from the palmar digital crease (mean, 2.45 +/- 0.03 cm). The mean absolute difference between these two, measured distances in each finger was 0.13 cm, with a 95 percent confidence interval of 0.11 to 0.14 cm. Thus, the distance between the palmar digital crease and the proximal interphalangeal crease can be used to predict the distance between the palmar digital crease and the Al pulley proximal edge with reasonable accuracy. Al pulley length averaged 0.98 +/- 0.02 cm for the small finger and 1.17 +/- 0.02 cm for the index, middle, and ring fingers. The length of the Al pulley was significantly shorter (p < 0.001) for the small finger than for the index, middle, and ring fingers. Additionally, a cruciate (CO) pulley was consistently located between the Al and A2 pulleys, an average of 0.46 cin proximal to the palmar digital crease, which can serve as guide for concluding the release of the Al pulley. Clinically, hand surface landmark ratios were used to release 32 trigger fingers with a minimally invasive technique, without a complication during 4- to 30-week follow-up. We conclude that hand surface landmark ratios can serve to locate the proximal Al pulley edge, thus facilitating complete trigger finger release by either open or minimally invasive techniques. Additionally, our study clarifies the discrepancy of prior smaller reports of the pulley system anatomy regarding the existence of the CO pulley between the Al and A2 pulleys. The cruciate fibers of this CO pulley can serve as the distal boundary for release of trigger finger.
C1 So Illinois Univ, Sch Med, Plast Surg Inst, Div Plast Surg, Springfield, IL 62794 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA.
RP Wilhelmi, BJ (reprint author), So Illinois Univ, Sch Med, Plast Surg Inst, Div Plast Surg, 747 N Rutledge,POB 19653, Springfield, IL 62794 USA.
NR 28
TC 30
Z9 36
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0032-1052
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD SEP 15
PY 2001
VL 108
IS 4
BP 908
EP 915
DI 10.1097/00006534-200109150-00014
PG 8
WC Surgery
SC Surgery
GA 470YY
UT WOS:000170901100014
PM 11547146
ER

PT J
AU Gargollo, P
   Yamada, K
   Esnaola, N
   Fuchimoto, Y
   Newell, KL
   Sachs, DH
   Huang, CA
AF Gargollo, P
   Yamada, K
   Esnaola, N
   Fuchimoto, Y
   Newell, KL
   Sachs, DH
   Huang, CA
TI Neuropathy in miniature swine after administration of the mutant
   diphtheria toxin-based immunotoxin, pCD3-CRM9.
SO TRANSPLANTATION
LA English
DT Article
ID EPIDERMAL GROWTH-FACTOR; LARGE-ANIMAL-MODEL; T-CELL DEPLETION; MIXED
   CHIMERISM; BINDING; TOLERANCE; RECEPTOR; EGF; IRRADIATION; ANTIBODIES
AB Background. Effective in vivo T-cell depletion is a critical component of many transplantation tolerance protocols. We have previously demonstrated T-cell depletion in miniature swine using a CRM9-based CD3-immunotoxin, pCD3-CRM9. CRM9 is a mutant form of diphtheria toxin (DT) that binds less efficiently than wild-type DT to the DT receptor (proHB-EGF) of primates. In this report, we describe and characterize the dose-dependent neurotoxicity associated with CRM9-based immunotoxin administration in swine.
   Methods. Miniature swine were treated with varying doses of pCD3-CRM9 followed by daily monitoring for symptoms of neuropathy, including limb weakness, paresis, sluggishness, and/or respiratory distress. Animals demonstrating severe respiratory distress were euthanized and peripheral nerve, spinal cord, and skeletal muscle tissue samples were obtained at autopsy for microscopic examination. Unconjugated CRM9 was administered to one animal to define its toxicity independent of the effects of T-cell depletion.
   Results. Excellent T-cell depletion was obtained using doses of pCD3-CRM9 greater than 0.1 mg/kg. However, neurotoxicity was observed at these doses, as manifested by transient muscle weakness or paresis, which in some cases progressed to respiratory failure and death. Dorsal root ganglia samples revealed pathological changes typical of diphtheritic polyneuropathy. The animal receiving unconjugated CRM9 exhibited the same neurotoxic side effects as those receiving the pCD3-CRM9 conjugate.
   Conclusions. Administration of pCD3-CRM9 immunotoxin provides excellent T-cell depletion in miniature swine but is associated with significant dose-dependent neurotoxicity. A possible reason for CRM9-associated neurotoxicity in swine, but not primates, is suggested on the basis of a known amino acid difference in the exodomain of the DT receptor (proHB-EGF) of swine compared with that of primates.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA.
   Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Huang, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH-East,Bldg 149-9019,13th St, Boston, MA 02129 USA.
FU NHLBI NIH HHS [1R01 HL63430-01]; NIAID NIH HHS [P01 AI39755]
NR 27
TC 5
Z9 5
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 SEP 15
PY 2001
VL 72
IS 5
BP 818
EP 822
DI 10.1097/00007890-200109150-00013
PG 5
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA 474AW
UT WOS:000171083000013
PM 11571443
ER

PT J
AU Yoon, JC
   Puigserver, P
   Chen, GX
   Donovan, J
   Wu, ZD
   Rhee, J
   Adelmant, G
   Stafford, J
   Kahn, CR
   Granner, DK
   Newgard, CB
   Spiegelman, BM
AF Yoon, JC
   Puigserver, P
   Chen, GX
   Donovan, J
   Wu, ZD
   Rhee, J
   Adelmant, G
   Stafford, J
   Kahn, CR
   Granner, DK
   Newgard, CB
   Spiegelman, BM
TI Control of hepatic gluconeogenesis through the transcriptional
   coactivator PGC-1
SO NATURE
LA English
DT Article
ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; GLUCOSE-6-PHOSPHATASE CATALYTIC
   SUBUNIT; RECEPTOR-GAMMA COACTIVATOR-1; RESPONSE UNIT; GLUCOCORTICOID
   RESPONSE; NUCLEAR RECEPTORS; METABOLIC IMPACT; CAMP INDUCTION;
   BINDING-SITES; GTP GENE
AB Blood glucose levels are maintained by the balance between glucose uptake by peripheral tissues and glucose secretion by the liver. Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. Here we show that the transcriptional coactivator PGC-1 is strongly induced in liver in fasting mice and in three mouse models of insulin action deficiency: streptozotocin-induced diabetes, ob/ob genotype and liver insulin-receptor knockout. PGC-1 is induced synergistically in primary liver cultures by cyclic AMP and glucocorticoids. Adenoviral-mediated expression of PGC-1 in hepatocytes in culture or in vivo strongly activates an entire programme of key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, leading to increased glucose output. Full transcriptional activation of the PEPCK promoter requires coactivation of the glucocorticoid receptor and the liver-enriched transcription factor HNF-4 alpha (hepatic nuclear factor-4 alpha) by PGC-1. These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   Univ Texas, SW Med Ctr, Touchstone Ctr Diabet Res, Dept Biochem, Dallas, TX USA.
   Univ Texas, SW Med Ctr, Touchstone Ctr Diabet Res, Dept Internal Med, Dallas, TX USA.
   Vanderbilt Univ, Dept Mol Biol & Biophys, Sch Med, Nashville, TN 37232 USA.
   Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
NR 33
TC 1080
Z9 1133
U1 8
U2 75
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 13
PY 2001
VL 413
IS 6852
BP 131
EP 138
DI 10.1038/35093050
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 471FU
UT WOS:000170918800038
PM 11557972
ER

PT J
AU Herzig, S
   Long, FX
   Jhala, US
   Hedrick, S
   Quinn, R
   Bauer, A
   Rudolph, D
   Schutz, G
   Yoon, C
   Puigserver, P
   Spiegelman, B
   Montminy, M
AF Herzig, S
   Long, FX
   Jhala, US
   Hedrick, S
   Quinn, R
   Bauer, A
   Rudolph, D
   Schutz, G
   Yoon, C
   Puigserver, P
   Spiegelman, B
   Montminy, M
TI CREB regulates hepatic gluconeogenesis through the coactivator PGC-1
SO NATURE
LA English
DT Article
ID PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE; CAMP RESPONSE ELEMENT; GTP GENE;
   LEPTIN RECEPTOR; BINDING PROTEIN; TRANSCRIPTION; GLUCOCORTICOIDS;
   PROMOTER; MICE; IDENTIFICATION
AB When mammals fast, glucose homeostasis is achieved by triggering expression of gluconeogenic genes in response to glucagon and glucocorticoids. The pathways act synergistically to induce gluconeogenesis (glucose synthesis), although the underlying mechanism has not been determined(1-4). Here we show that mice carrying a targeted disruption of the cyclic AMP (cAMP) response element binding (CREB) protein gene, or overexpressing a dominant-negative CREB inhibitor, exhibit fasting hyperglycaemia and reduced expression of gluconeogenic enzymes. CREB was found to induce expression of the gluconeogenic programme through the nuclear receptor coactivator PGC-1, which is shown here to be a direct target for CREB regulation in vivo. Overexpression of PGC-1 in CREB-dercient mice restored glucose homeostasis and rescued expression of gluconeogenic genes. In transient assays, PGC-1 potentiated glucocorticoid induction of the gene for phosphoenolpyruvate carboxykinase (PEPCK), the rate-limiting enzyme in gluconeogenesis. PGC-1 promotes cooperativity between cyclic AMP and glucocorticoid signalling pathways during hepatic gluconeogenesis. Fasting hyperglycaemia is strongly correlated with type II diabetes, so our results suggest that the activation of PGC-1 by CREB in liver contributes importantly to the pathogenesis of this disease.
C1 Salk Inst Biol Studies, Peptide Biol Labs, La Jolla, CA 92037 USA.
   Joslin Diabet Ctr, Boston, MA 02215 USA.
   Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA.
RP Montminy, M (reprint author), Salk Inst Biol Studies, Peptide Biol Labs, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA.
OI Herzig, Stephan/0000-0003-3950-3652
NR 29
TC 772
Z9 794
U1 5
U2 48
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 13
PY 2001
VL 413
IS 6852
BP 179
EP 183
DI 10.1038/35093131
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 471FU
UT WOS:000170918800050
PM 11557984
ER

PT J
AU Chung, RT
   Varghese, JC
   Berger, DL
AF Chung, RT
   Varghese, JC
   Berger, DL
TI A 44-year-old woman with chills, fever, jaundice, and hepatic abscesses.
   Recurrent pyogenic cholangitis (Oriental cholangiohepatitis).
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID PRIMARY SCLEROSING CHOLANGITIS; ULCERATIVE-COLITIS; ASSOCIATION;
   DISEASE; GALLSTONES
C1 Massachusetts Gen Hosp, Liver Transplant Program, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Chung, RT (reprint author), Massachusetts Gen Hosp, Liver Transplant Program, Boston, MA 02114 USA.
NR 30
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD SEP 13
PY 2001
VL 345
IS 11
BP 817
EP 823
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 471BK
UT WOS:000170906800008
ER

PT J
AU Linder, JA
   Stafford, RS
AF Linder, JA
   Stafford, RS
TI Antibiotic treatment of adults with sore throat by community primary
   care physicians - A national survey, 1989-1999
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article; Proceedings Paper
CT 24th Annual Meeting of the Society-of-General-Internal-Medicine
CY MAY   04, 2001
CL SAN DIEGO, CALIFORNIA
SP Soc Gen Internal Med
ID RESPIRATORY-TRACT INFECTIONS; GROUP-A STREPTOCOCCI; ERYTHROMYCIN
   RESISTANCE; PHARYNGITIS; SUSCEPTIBILITY; MANAGEMENT; BRONCHITIS;
   PENICILLIN; DIAGNOSIS; PYOGENES
AB Context Most sore throats are due to viral upper respiratory tract infections. Group A beta -hemolytic streptococci (GABHS), the only common cause of sore throat warranting antibiotics, is cultured in 5% to 17% of adults with sore throat. The frequency of antibiotic use for pharyngitis has greatly exceeded the prevalence of GABHS, but less is known about specific classes of antibiotics used. Only penicillin and erythromycin are recommended as first-line antibiotics against GABHS.
   Objectives To measure trends in antibiotic use for adults with sore throat and to determine predictors of antibiotic use and nonrecommended antibiotic use.
   Design, Setting, and Subjects Retrospective analysis of 2244 visits to primary care physicians in off ice-based practices in the National Ambulatory Medical Care Survey, 1989-1999, by adults with a chief complaint of sore throat.
   Main Outcome Measures Treatment with antibiotics and treatment with nonrecommended antibiotics, extrapolated to US annual national rates.
   Results There were an estimated 6.7 million annual visits in the United States by adults with sore throat between 1989 and 1999. Antibiotics were used in 73% (95% confidence interval [CI] 70%-76%) of visits. Patients treated with antibiotics were given nonrecommended antibiotics in 68% (95% CI, 64%-72%) of visits. From 1989 to 1999, there was a significant decrease in use of penicillin and erythromycin and an increase in use of nonrecommended antibiotics, especially extended-spectrum macrolides and extended-spectrum fluoroquinolones (P<.001 for all trends). In multivariable modeling, increasing patient age (odds ratio [OR], 0.86 per decade; 95% CI, 0.79-0.94) and general practice specialty (OR, 1.54 compared with family practice specialty; 95% CI, 1.10-2.14) were independent predictors of antibiotic use. Among patients receiving antibiotics, nonrecommended antibiotic use became more frequent over time (OR, 1.17 per year; 95% CI, 1.11-1.24).
   Conclusions More than half of adults are treated with antibiotics for sore throat by community primary care physicians. Use of nonrecommended, more expensive, broader-spectrum antibiotics is frequent.
C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
   Stanford Univ, Sch Med, Stanford Ctr Res Dis Prevent, Palo Alto, CA 94304 USA.
RP Linder, JA (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
FU BHP HRSA HHS [5T32PE11001-12]; NHLBI NIH HHS [K08-HL03548]
NR 34
TC 112
Z9 119
U1 1
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610 USA
SN 0098-7484
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD SEP 12
PY 2001
VL 286
IS 10
BP 1181
EP 1186
DI 10.1001/jama.286.10.1181
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA 471CR
UT WOS:000170910400027
PM 11559262
ER

PT J
AU Rinaldi, MJ
   Piana, RN
   Caputo, RP
   Gordon, PC
   Lopez, JJ
   Dauerman, HL
   Hammes, LN
   Holmes, DR
   Shaikh, SR
   Ryan, T
   Warner, JJ
   Zidar, JP
   Kiernan, FJ
   Moussa, I
   Palacios, IF
   Cox, DA
   Lim, J
   Murphy, S
   Cutlip, DE
   Ho, KKL
   Gibson, M
   Cohen, DJ
AF Rinaldi, MJ
   Piana, RN
   Caputo, RP
   Gordon, PC
   Lopez, JJ
   Dauerman, HL
   Hammes, LN
   Holmes, DR
   Shaikh, SR
   Ryan, T
   Warner, JJ
   Zidar, JP
   Kiernan, FJ
   Moussa, I
   Palacios, IF
   Cox, DA
   Lim, J
   Murphy, S
   Cutlip, DE
   Ho, KKL
   Gibson, M
   Cohen, DJ
TI Multicenter study of stent thrombosis in the modern era.
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
   Vanderbilt Univ, Med Ctr, Nashville, TN USA.
   SJH Cardiol Associates, Syracuse, NY USA.
   Miriam Hosp, Providence, RI 02906 USA.
   Univ Iowa, Med Ctr, Iowa City, IA USA.
   Univ Massachusetts, Med Ctr, Worcester, MA USA.
   Mayo Clin, Rochester, MN USA.
   Maine Med Ctr, Portland, ME 04102 USA.
   Duke Univ, Med Ctr, Durham, NC USA.
   Hartford Hosp, Hartford, CT 06115 USA.
   Lenox Hill Hosp, New York, NY 10021 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Presbyterian Hosp, Charlotte, NC USA.
   Perfuse Core Lab, Boston, MA USA.
   Harvard Univ, Clin Res Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU EXCERPTA MEDICA INC
PI NEW YORK
PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD SEP 11
PY 2001
VL 88
IS 5A
SU S
MA TCT11
BP 4G
EP 5G
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 470WF
UT WOS:000170893600013
ER

PT J
AU Harding, SA
   Hourigan, LA
   Walters, DL
   Keck, SA
   Dec, GW
   Semigran, MJ
AF Harding, SA
   Hourigan, LA
   Walters, DL
   Keck, SA
   Dec, GW
   Semigran, MJ
TI Percutaneous coronary intervention for cardiac transplant vasculopathy
   improves left ventricular function despite a high rate of restenosis.
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Meeting Abstract
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU EXCERPTA MEDICA INC
PI NEW YORK
PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD SEP 11
PY 2001
VL 88
IS 5A
SU S
MA TCT312
BP 121G
EP 122G
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 470WF
UT WOS:000170893600311
ER

PT J
AU Scherrer-Crosbie, M
   Ullrich, R
   Bloch, KD
   Nakajima, H
   Nasseri, B
   Aretz, HT
   Lindsey, ML
   Vancon, AC
   Huang, PL
   Lee, RT
   Zapol, WM
   Picard, MH
AF Scherrer-Crosbie, M
   Ullrich, R
   Bloch, KD
   Nakajima, H
   Nasseri, B
   Aretz, HT
   Lindsey, ML
   Vancon, AC
   Huang, PL
   Lee, RT
   Zapol, WM
   Picard, MH
TI Endothelial nitric oxide synthase limits left ventricular remodeling
   after myocardial infarction in mice
SO CIRCULATION
LA English
DT Article
DE echocardiography; ventricles; hypertrophy
ID ISCHEMIA-REPERFUSION INJURY; ECHOCARDIOGRAPHIC ASSESSMENT; GENE; RATS;
   POLYMORPHISM; DYSFUNCTION; INHIBITOR; SURVIVAL; SIZE; NO
AB Background-To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling after myocardial infarction (MI), the impact of left anterior descending coronary artery ligation on IV size and function was compared in 2- to 4-month-old wild-type (WT) and NOS3-deficient mice (NOS3(-/-)).
   Methods and Results-Two days after MI, both strains of mice had a similar LV size, fractional shortening, and ejection fraction by echocardiography. Twenty-eight days after MI, both strains had dilated LVs with decreased fractional shortening and lower ejection fractions. Although the infarcted fraction of the LV was similar in both strains, LV end-diastolic internal diameter, end-diastolic volume, and mass were greater, but fractional shortening, ejection fraction, and the maximum rate of developed LV pressure (dP/dt(max)) were lower in NOS3(-/-) than in WT mice. Impairment of diastolic function, as measured by the time constant of isovolumic relaxation (tau) and the maximum rate of LV pressure decay (dP/dt(min)), was more marked in NOS3(-/-) than in WT mice. Mortality after MI was greater in NOS3(-/-) than in WT mice. Long-term administration of hydralazine normalized blood pressure in NOS3(-/-) mice, but it did not prevent the IV dilatation, impaired systolic and diastolic function, and increased LV mass that followed MI. In WT mice, capillary density and myocyte width in the nonischemic portion of the IV did not differ before and 28 days after MI, whereas in NOS3(-/-) mice, capillary density decreased and myocyte width increased after MI, whether or not hydralazine was administered.
   Conclusions-These results suggest that the presence of NOS3 limits LV dysfunction and remodeling in a murine model of MI by an afterload-independent mechanism, in part by decreasing myocyte hypertrophy in the remote myocardium.
C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
   Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 32 Fruit St, Boston, MA 02114 USA.
RI Lindsey, Merry/B-2650-2012; 
OI Picard, Michael/0000-0002-9264-3243
FU NHLBI NIH HHS [HL-42397, HL-57172]
NR 27
TC 202
Z9 213
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 SEP 11
PY 2001
VL 104
IS 11
BP 1286
EP 1291
DI 10.1161/hc3601.094298
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 472TC
UT WOS:000171000200024
PM 11551881
ER

PT J
AU Miller, BL
   Seeley, WW
   Mychack, P
   Rosen, HJ
   Mena, I
   Boone, K
AF Miller, BL
   Seeley, WW
   Mychack, P
   Rosen, HJ
   Mena, I
   Boone, K
TI Neuroanatomy of the self - Evidence from patients with frontotemporal
   dementia
SO NEUROLOGY
LA English
DT Article
ID EPISODIC MEMORY; FRONTAL-LOBE; ALZHEIMERS-DISEASE; RETROGRADE-AMNESIA;
   INFORMATION; DEGENERATION; KNOWLEDGE; EMERGENCE; PET
AB Objective: To evaluate the frequency and types of change in "self" seen in frontotemporal dementia (FTD) and to determine the relative involvement of the nondominant and dominant frontal and temporal brain regions in FTD patients with or without changes in a sense of self using neuropsychology tests and neuroimaging. Background: The self has been defined as "the total, essential, or particular being of a person" involving "the essential qualities distinguishing one person from another." Some suggest that the frontal lobes play a dominant role in maintaining the self FTD affects anterior frontal and temporal areas and can be associated with a loss of self. Methods: Seventy-two consecutive FTD patients were evaluated with neuropsychiatric, neuropsychologic, and behavioral measures. Patients were imaged with MRI and SPECT. Charts were reviewed by a social psychologist to determine patients who exhibited a dramatic change in their self as defined by changes in political, social, or religious values. The brain areas with the most severe atrophy or hypoperfusion on neuroimaging were noted. Results: Seven of 72 patients exhibited a dramatic change in self. In six of the seven, the selective dysfunction involved the nondominant frontal region. In contrast, only one of the other 65 patients without selective nondominant frontal dysfunction showed a change in self. Conclusions: FTD patients with asymmetric loss of function in the nondominant frontal lobe often exhibit a diminished maintenance of previously learned self-concepts despite intact memory and language. Normal nondominant frontal function is important for the maintenance of the self.
C1 UCSF, Sch Med, Dept Neurol, San Francisco, CA 94117 USA.
   Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
   Clin Las Condes, Dept Nucl Med, Santiago, Chile.
   Univ Calif Los Angeles, Sch Med, Harbor UCLA Med Ctr, Dept Psychiat, Torrance, CA 90509 USA.
   UCSF, Memory & Aging Clin, San Francisco, CA USA.
RP Miller, BL (reprint author), UCSF, Sch Med, Dept Neurol, 350 Parnassus Ave,Suite 800, San Francisco, CA 94117 USA.
EM bmiller@memory.ucsf.edu
NR 33
TC 128
Z9 129
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD SEP 11
PY 2001
VL 57
IS 5
BP 817
EP 821
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA 470TE
UT WOS:000170886600014
PM 11552010
ER

PT J
AU Lederkremer, GZ
   Cheng, YF
   Petre, BM
   Vogan, E
   Springer, S
   Schekman, R
   Walz, T
   Kirchhausen, T
AF Lederkremer, GZ
   Cheng, YF
   Petre, BM
   Vogan, E
   Springer, S
   Schekman, R
   Walz, T
   Kirchhausen, T
TI Structure of the Sec23p/24p and Sec13p/31p complexes of COPII
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID ENDOPLASMIC-RETICULUM; VESICLE FORMATION; COAT PROTEINS; MEMBRANE; ER
AB COPII-coated vesicles carry proteins from the endoplasmic reticulum to the Golgi complex. This vesicular transport can be reconstituted by using three cytosolic components containing five proteins: the small GTPase Sar1p, the Sec23p/24p complex, and the Sec13p/Sec31p complex. We have used a combination of biochemistry and electron microscopy to investigate the molecular organization and structure of Sec23p/24p and Sec13p/31p complexes. The three-dimensional reconstruction of Sec23p/24p reveals that it has a bone-shaped structure, (17 nm in length), composed of two similar globular domains, one corresponding to Sec23p and the other to Sec24p. Sec13p/31p is a heterotetramer composed of two copies of Sec13p and two copies of Sec31p. It has an elongated shape, is 28-30 nm in length, and contains five consecutive globular domains linked by relatively flexible joints. Putting together the architecture of these Sec complexes with the interactions between their subunits and the appearance of the coat in COPII-coated vesicles, we present a model for COPII-coat organization.
C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Biochem Chem & Mol Pharmacol, Boston, MA 02115 USA.
   Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
   Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
FU NIGMS NIH HHS [GM36548, GM62580-01, P01 GM062580, R01 GM036548]
NR 19
TC 94
Z9 100
U1 0
U2 4
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 11
PY 2001
VL 98
IS 19
BP 10704
EP 10709
DI 10.1073/pnas.191359398
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 472CZ
UT WOS:000170966800039
PM 11535824
ER

PT J
AU Staunton, JE
   Slonim, DK
   Coller, HA
   Tamayo, P
   Angelo, MJ
   Park, J
   Scherf, U
   Lee, JK
   Reinhold, WO
   Weinstein, JN
   Mesirov, JP
   Lander, ES
   Golub, TR
AF Staunton, JE
   Slonim, DK
   Coller, HA
   Tamayo, P
   Angelo, MJ
   Park, J
   Scherf, U
   Lee, JK
   Reinhold, WO
   Weinstein, JN
   Mesirov, JP
   Lander, ES
   Golub, TR
TI Chemosensitivity prediction by transcriptional profiling
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID ANTICANCER DRUG SCREEN; MOLECULAR CLASSIFICATION; CELL LINES;
   EXPRESSION; CANCER; PHARMACOLOGY; DISCOVERY
AB in an effort to develop a genomics-based approach to the prediction of drug response, we have developed an algorithm for classification of cell line chemosensitivity based on gene expression profiles alone. Using oligonucleotide microarrays, the expression levels of 6,817 genes were measured in a panel of 60 human cancer cell lines (the NCl-60) for which the chemosensitivity profiles of thousands of chemical compounds have been determined. We sought to determine whether the gene expression signatures of untreated cells were sufficient for the prediction of chemosensitivity. Gene expression-based classifiers of sensitivity or resistance for 232 compounds were generated and then evaluated on independent sets of data. The classifiers were designed to be independent of the cells' tissue of origin. The accuracy of chemosensitivity prediction was considerably better than would be expected by chance. Eighty-eight of 232 expression-based classifiers performed accurately (with P < 0.05) on an independent test set, whereas only 12 of the 232 would be expected to do so by chance. These results suggest that at least for a subset of compounds genomic approaches to chemosensitivity prediction are feasible.
C1 Whitehead MIT, Ctr Genome Res, Cambridge, MA 02139 USA.
   NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA.
   MIT, Dept Biol, Cambridge, MA 02139 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Lander, ES (reprint author), Whitehead MIT, Ctr Genome Res, Cambridge, MA 02139 USA.
EM lander@wi.mit.edu; golub@genome.wi.mit.edu
NR 16
TC 439
Z9 459
U1 0
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 SEP 11
PY 2001
VL 98
IS 19
BP 10787
EP 10792
DI 10.1073/pnas.191368598
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 472CZ
UT WOS:000170966800053
PM 11553813
ER

PT J
AU Wang, JH
   Meijers, R
   Xiong, Y
   Liu, JH
   Sakihama, T
   Zhang, RG
   Joachimiak, A
   Reinherz, EL
AF Wang, JH
   Meijers, R
   Xiong, Y
   Liu, JH
   Sakihama, T
   Zhang, RG
   Joachimiak, A
   Reinherz, EL
TI Crystal structure of the human CD4 N-terminal two-domain fragment
   complexed to a class II MHC molecule
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID T-CELL ACTIVATION; IMMUNODEFICIENCY-VIRUS GP120; ENVELOPE GLYCOPROTEIN;
   BETA-CHAINS; BINDING; RECEPTOR; ANTIGENS; ALPHA; CD8-ALPHA-ALPHA;
   OLIGOMERIZATION
AB The structural basis of the interaction between the CD4 coreceptor and a class II major histocompatibility complex (MHC) is described. The crystal structure of a complex containing the human CD4 N-terminal two-domain fragment and the murine I-A(k) class II MHC molecule with associated peptide (pMHCII) shows that only the "top corner" of the CD4 molecule directly contacts pMHCII. The CD4 Phe-43 side chain extends into a hydrophobic concavity formed by MHC residues from both alpha2 and beta2 domains. A ternary model of the CD4-pMHCII-T-cell receptor (TCR) reveals that the complex appears V-shaped with the membrane-proximal pMHCII at the apex. This configuration excludes a direct TCR-CD4 interaction and suggests how TCR and CD4 signaling is coordinated around the antigenic pMHCII complex. Human CD4 binds to HIV gp120 in a manner strikingly similar to the way in which CD4 interacts with pMHCII. Additional contacts between gp120 and CD4 give the CD4-gp120 complex a greater affinity. Thus, ligation of the viral envelope glycoprotein to CD4 occludes the pMHCII-binding site on CD4, contributing to immunodeficiency.
C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Mol Pharmacol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA.
   Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA.
RP Wang, JH (reprint author), Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA.
RI Meijers, Rob/D-5521-2011; 
OI Meijers, Rob/0000-0003-2872-6279
NR 47
TC 156
Z9 163
U1 0
U2 3
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD SEP 11
PY 2001
VL 98
IS 19
BP 10799
EP 10804
DI 10.1073/pnas.191124098
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 472CZ
UT WOS:000170966800055
PM 11535811
ER

PT J
AU Lu, QR
   Park, JK
   Noll, E
   Chan, JA
   Alberta, J
   Yuk, D
   Alzamora, MG
   Louis, DN
   Stiles, CD
   Rowitch, DH
   Black, PM
AF Lu, QR
   Park, JK
   Noll, E
   Chan, JA
   Alberta, J
   Yuk, D
   Alzamora, MG
   Louis, DN
   Stiles, CD
   Rowitch, DH
   Black, PM
TI Oligodendrocyte lineage genes (OLIG) as molecular markers for human
   glial brain tumors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID SONIC HEDGEHOG; SUCCESSFUL CHEMOTHERAPY; PROGENITOR-CELL;
   NERVOUS-SYSTEM; PRECURSOR CELL; GLIOMAS; EXPRESSION; CEREBELLUM;
   SURVIVAL; ANTIGENS
AB The most common primary tumors of the human brain are thought to be of glial cell origin. However, glial cell neoplasms cannot be fully classified by cellular morphology or with conventional markers for astrocytes, oligodendrocytes, or their progenitors. Recent insights into central nervous system tumorigenesis suggest that novel molecular markers might be found among factors that have roles in glial development. Oligodendrocyte lineage genes (Olig1/2)encode basic helix-loop-helix transcription factors. In the rodent central nervous system, they are expressed exclusively in oligodendrocytes and oligodendrocyte progenitors, and Olig1 can promote formation of an chondroitin sulfate proteoglycon-positive glial progenitor. Here we show that human OLIG genes are expressed strongly in oligodendroglioma, contrasting absent or low expression in astrocytoma. Our data provide evidence that neoplastic cells of oligodendroglioma resemble oligodendrocytes or their progenitor cells and may derive from cells of this lineage. They further suggest the diagnostic potential of OLIG markers to augment identification of oligodendroglial tumors.
C1 Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Dept Canc Biol, Program Neurooncol, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Dept Pediat Oncol, Program Neurooncol, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Dept Neuropathol, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA.
   Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA.
   Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA.
RP Stiles, CD (reprint author), Dana Farber Canc Inst, Dana Farber Harvard Canc Ctr, Dept Canc Biol, Program Neurooncol, 44 Binney St, Boston, MA 02115 USA.
FU NCI NIH HHS [R01 CA057683, CA 57683]; NICHD NIH HHS [HD24296]; NINDS NIH
   HHS [NS41764]
NR 33
TC 119
Z9 125
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 SEP 11
PY 2001
VL 98
IS 19
BP 10851
EP 10856
DI 10.1073/pnas.181340798
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 472CZ
UT WOS:000170966800064
PM 11526205
ER

PT J
AU Garsin, DA
   Sifri, CD
   Mylonakis, E
   Qin, X
   Singh, KV
   Murray, BE
   Calderwood, SB
   Ausubel, FM
AF Garsin, DA
   Sifri, CD
   Mylonakis, E
   Qin, X
   Singh, KV
   Murray, BE
   Calderwood, SB
   Ausubel, FM
TI A simple model host for identifying Gram-positive virulence factors
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
   AMERICA
LA English
DT Article
ID ENTEROCOCCUS-FAECALIS ENDOPHTHALMITIS; BACTERIAL SEX-PHEROMONE;
   CAENORHABDITIS-ELEGANS; PSEUDOMONAS-AERUGINOSA; STREPTOCOCCUS-MUTANS;
   AGGREGATION SUBSTANCE; PATHOGENESIS; HEMOLYSIN; ENDOCARDITIS;
   PERITONITIS
AB We demonstrate the use of the nematode Caenorhabditis elegans as a facile and inexpensive model host for several Gram-positive human bacterial pathogens. Enterococcus faecalis, Streptococcus pneumoniae, and Staphylococcus aureus, but not Bacillus subtilis, Enterococcus faecium, or Streptococcus pyogenes, kill adult C elegans. Focusing our studies on the enterococcal species, we found that both E. faecalis and E. faecium kill C elegans eggs and hatchlings, although only E. faecalis kills the adults. In the case of adults, a low inoculum of E, faecalis grows to a high titer in the C elegans intestine, resulting in a persistent infection that cannot be eradicated by prolonged feeding on E. faecium. Interestingly, a high titer of E. faecium also accumulates in the nematode gut, but does not affect the longevity of the worms. Two E. faecalis virulence-related factors that play an important role in mammalian models of infection, tsr, a putative quorum-sensing system, and cytolysin, are also important for nematode killing. We exploit the apparent parallels between Gram-positive infection in simple and more complex organisms by using the nematode to identify an E. faecalis virulence factor, ScrB, which is relevant to mammalian pathogenesis.
C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
   Univ Texas, Sch Med, Dept Med, Div Infect Dis, Houston, TX 77030 USA.
   Univ Texas, Sch Med, Dept Microbiol & Mol Genet, Houston, TX 77030 USA.
   Univ Texas, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Houston, TX 77030 USA.
   Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
FU NIAID NIH HHS [AI47923, AI42399, R01 AI042399, R01 AI047923, R37
   AI047923, R56 AI042399]
NR 27
TC 310
Z9 319
U1 3
U2 19
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 SEP 11
PY 2001
VL 98
IS 19
BP 10892
EP 10897
DI 10.1073/pnas.191378698
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 472CZ
UT WOS:000170966800071
PM 11535834
ER

PT J
AU Ferguson, DO
   Alt, FW
AF Ferguson, DO
   Alt, FW
TI DNA double strand break repair and chromosomal translocation: Lessons
   from animal models
SO ONCOGENE
LA English
DT Article
DE translocation; non-homologous end joining; homologous recombination;
   double strand break repair; loss of heterozygosity; oncogenesis
ID END-JOINING PATHWAY; V(D)J RECOMBINATION; NONRECIPROCAL TRANSLOCATIONS;
   GENOMIC STABILITY; VERTEBRATE CELLS; MAMMALIAN-CELLS; TUMOR-FORMATION;
   TUMORIGENESIS; PROTEINS; MICE
AB The maintenance of genomic stability is one of the most important defenses against neoplastic transformation. This objective must be accomplished despite a constant barrage of spontaneous DNA double strand breaks. These dangerous lesions are corrected by two primary pathways of double strand break repair; non homologous end joining and homologous recombination. Recent studies employing mouse models have shown that absence of either pathway leads to genomic instability, including potentially oncogenic translocations. Because translocations involve the union of different chromosomes, cellular machinery must exist that creates these structures in the context of unrepaired double strand breaks. Evidence is mounting that the pathways of double strand break repair that are so important for survival may themselves be the culprits that generate potentially fatal translocations. Evidence and models for the dual roles of double strand break repair in both preventing, and generating, oncogenic karyotypic changes are discussed.
C1 Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Enders Bldg,Room 861,Mail Stop EN-334,320 Longwoo, Boston, MA 02115 USA.
NR 52
TC 215
Z9 229
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD SEP 10
PY 2001
VL 20
IS 40
BP 5572
EP 5579
DI 10.1038/sj.onc.1204767
PG 8
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 470TP
UT WOS:000170887500001
PM 11607810
ER

PT J
AU Seidel, MG
   Look, AT
AF Seidel, MG
   Look, AT
TI E2A-HLF usurps control of evolutionarily conserved survival pathways
SO ONCOGENE
LA English
DT Article
DE apoptosis; acute leukemia; chromosomal translocation; circadian rhythm;
   hepatic leukemia factor; developmental cell fate
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; LOOP-HELIX PROTEINS; ZINC-FINGER PROTEIN;
   CHIMERIC TRANSCRIPTION FACTOR; LEUCINE-ZIPPER PROTEINS; PROGRAMMED
   CELL-DEATH; DNA-BINDING PROTEINS; FUSION MESSENGER-RNA; PRO-B
   LYMPHOCYTES; C-ELEGANS
AB E2A-HLF, the chimeric fusion protein resulting from the leukemogenic translocation t(17;19), appears to employ evolutionarily conserved signaling cascades for its transforming and antiapoptotic functions. These arise from both impairment of normal E2A function and activation of a survival pathway triggered through the HLF bZip DNA binding and dimerization domain. Recent reports identify wild-type E2A as a tumor suppressor in T lymphocytes. Moreover, E2A-HLF has been shown to activate SLUG, a mammalian homologue of the cell death specification protein CES-1 in Caenorhabditis elegans, which appears to regulate an evolutionarily conserved cell survival program. Recently, several key mouse models have been generated, enabling further elucidation of these pathways on a molecular genetic level in vivo. In this review, we discuss the characteristics of both components of the fusion protein with regard to their contribution to the regulation of cell fate and the oncogenic potential of E2A-HLF.
C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,M-630, Boston, MA 02115 USA.
NR 97
TC 23
Z9 24
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD SEP 10
PY 2001
VL 20
IS 40
BP 5718
EP 5725
DI 10.1038/sj.onc.1204591
PG 8
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 470TP
UT WOS:000170887500012
PM 11607821
ER

PT J
AU Choudhury, GG
   Zhang, JH
   Ghosh-Choudhury, N
   Abboud, HE
AF Choudhury, GG
   Zhang, JH
   Ghosh-Choudhury, N
   Abboud, HE
TI Ceramide blocks PDGF-induced DNA synthesis in mesangial cells via
   inhibition of Akt kinase in the absence of apoptosis
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE PDGF; PI 3 kinase; Akt kinase; ceramide; c-fos; apoptosis
ID GROWTH-FACTOR RECEPTORS; NECROSIS-FACTOR-ALPHA; PROTEIN PHOSPHATASE;
   PHOSPHATIDYLINOSITOL-3 KINASE; SPHINGOMYELIN TURNOVER;
   CELLULAR-RESPONSES; PHOSPHORYLATION; ACTIVATION; DEATH; DIFFERENTIATION
AB The mechanism of action of ceramide in glomerular mesangial cells has not been studied. We investigated the effect of C2 ceramide on the mitogenic signal transduction pathways induced by PDGF in mesangial cells. Increasing concentrations of C2 ceramide inhibited PDGF-induced DNA synthesis in a dose-dependent manner with maximum inhibition at 15 muM. This inhibition of DNA synthesis was associated with attenuation of PDGF-induced early response gene c-fos transcription. PDGF receptor beta immunecomplex kinase assay showed no inhibitory effect of C2 ceramide on PDGF receptor tyrosine kinase activity. We have recently shown that the mitogenic effect of PDGF is mediated by the enzyme phosphatidylinositol (PI) 3 kinase in mesangial cells. C2 ceramide had no effect on PDGF-induced PDGFR-associated PI 3 kinase activity. These data indicate that inhibitory effect of C2 on PDGF-induced DNA synthesis is likely due to post-receptor and post-PI 3 kinase events. To address the mechanism of C2-mediated inhibition of DNA synthesis, we investigated the downstream target of PI 3 kinase, Akt. PDGF time-dependently increased Akt kinase activity in a PI 3 kinase-dependent manner. Incubation of mesangial cells with C2 ceramide inhibited PDGF-induced Akt activity. Akt kinase inhibits apoptosis of cells via phosphorylation of multiple pro-apoptotic proteins. However, inhibition of Akt activity by C2 ceramide did not induce apoptosis in mesangial cells. These data provide the first evidence that in mesangial cells, ceramide cross-talks with PI 3 kinase-dependent Akt kinase to inhibit PDGF-induced DNA synthesis without inducing apoptosis. (C) 2001 Academic Press.
C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA.
   Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA.
   Audie L Murphy Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA.
   S Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM choudhuryg@uthscsa.edu
NR 57
TC 6
Z9 6
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD SEP 7
PY 2001
VL 286
IS 5
BP 1183
EP 1190
DI 10.1006/bbrc.2001.5483
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 472CT
UT WOS:000170966200052
ER

PT J
AU Hietakangas, V
   Elo, I
   Rosenstrom, H
   Coffey, ET
   Kyriakis, JM
   Eriksson, JE
   Sistonen, L
AF Hietakangas, V
   Elo, I
   Rosenstrom, H
   Coffey, ET
   Kyriakis, JM
   Eriksson, JE
   Sistonen, L
TI Activation of the MKK4-JNK pathway during erythroid differentiation of
   K562 cells is inhibited by the heat shock factor 2-beta isoform
SO FEBS LETTERS
LA English
DT Article
DE heat shock factor 2; JNK/SAPK; erythroid differentiation; hemin; K562
   cell; mitogen-activated protein kinase
ID GENE-EXPRESSION; C-JUN; MAP KINASE; LINE K562; JNK; ERYTHROPOIETIN
AB In this study we report the activation of e-Jun terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
C1 Univ Turku, Abo Akad Univ, Turku Ctr Biotechnol, FIN-20521 Turku, Finland.
   Univ Turku, Dept Biochem & Food Chem, Turku, Finland.
   Abo Akad Univ, Dept Biol, SF-20500 Turku, Finland.
   Univ Turku, Dept Biol, SF-20500 Turku, Finland.
   Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA 02129 USA.
RP Sistonen, L (reprint author), Univ Turku, Abo Akad Univ, Turku Ctr Biotechnol, POB 123, FIN-20521 Turku, Finland.
NR 26
TC 5
Z9 7
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
J9 FEBS LETT
JI FEBS Lett.
PD SEP 7
PY 2001
VL 505
IS 1
BP 168
EP 172
DI 10.1016/S0014-5793(01)02810-1
PG 5
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 474BJ
UT WOS:000171084200033
PM 11557063
ER

PT J
AU Silverman, GA
   Bird, PI
   Carrell, RW
   Church, FC
   Coughlin, PB
   Gettins, PGW
   Irving, JA
   Lomas, DA
   Luke, CJ
   Moyer, RW
   Pemberton, PA
   Remold-O'Donnell, E
   Salvesen, GS
   Travis, J
   Whisstock, JC
AF Silverman, GA
   Bird, PI
   Carrell, RW
   Church, FC
   Coughlin, PB
   Gettins, PGW
   Irving, JA
   Lomas, DA
   Luke, CJ
   Moyer, RW
   Pemberton, PA
   Remold-O'Donnell, E
   Salvesen, GS
   Travis, J
   Whisstock, JC
TI The serpins are an expanding superfamily of structurally similar but
   functionally diverse proteins - Evolution, mechanism of inhibition,
   novel functions, and a revised nomenclature
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID PLASMINOGEN-ACTIVATOR INHIBITOR-2; CROSS-CLASS INHIBITION; ELASTASE
   INHIBITOR; INDUCED APOPTOSIS; POTENT INHIBITOR; TYPE-2; IDENTIFICATION;
   ANGIOGENESIS; NEUROSERPIN; INSERTION
C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Div Newborn Med, Boston, MA 02115 USA.
   Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic 3800, Australia.
   Univ Cambridge, Wellcome Trust Ctr Mol Mechanisms Dis, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 2XY, England.
   Univ Cambridge, Wellcome Trust Ctr Mol Mechanisms Dis, Cambridge Inst Med Res, Dept Med, Cambridge CB2 2XY, England.
   Univ N Carolina, Div Hematol Oncol Med, Chapel Hill, NC 27599 USA.
   Monash Univ, Box Hill Hosp, Dept Med, Melbourne, Vic 3128, Australia.
   Univ Illinois, Dept Biochem & Mol Biol, Chicago, IL 60612 USA.
   Univ Florida, Coll Med, Dept Microbiol & Mol Genet, Gainesville, FL 32610 USA.
   Arriva Pharmaceut, Alameda, CA 94501 USA.
   Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA.
   Burnham Inst, La Jolla, CA 92037 USA.
   Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA.
RP Silverman, GA (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Div Newborn Med, 300 Longwood Ave,Enders 970, Boston, MA 02115 USA.
RI Irving, James/I-8467-2015
NR 41
TC 785
Z9 811
U1 5
U2 53
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 SEP 7
PY 2001
VL 276
IS 36
BP 33293
EP 33296
DI 10.1074/jbc.R100016200
PG 4
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 471CP
UT WOS:000170910200001
PM 11435447
ER

PT J
AU Thompson, PR
   Kurooka, H
   Nakatani, Y
   Cole, PA
AF Thompson, PR
   Kurooka, H
   Nakatani, Y
   Cole, PA
TI Transcriptional coactivator protein p300 - Kinetic characterization of
   its histone acetyltransferase activity
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID SEROTONIN N-ACETYLTRANSFERASE; CATALYTIC MECHANISM; P300/CBP-ASSOCIATED
   FACTOR; FACTOR GATA-1; ACETYLATION; CBP; BINDING; SUBSTRATE; SITES; PCAF
AB The p300/cAMP response element-binding protein-binding protein (CBP) family members include human p300 and cAMP response element-binding protein-binding protein, which are both important transcriptional coactivators and histone acetyltransferases. Although the role of these enzymes in transcriptional regulation has been extensively documented, the molecular mechanisms of p300 and CBP histone acetyltransferase catalysis are poorly understood. Herein, we describe the first detailed kinetic characterization of p300 using full-length purified recombinant enzyme. These studies have employed peptide substrates to systematically examine the substrate specificity requirements and the kinetic mechanism of this enzyme. The importance of nearby positively charged residues in lysine targeting was demonstrated. The strict structural requirement of the lysine side chain was shown. The catalytic mechanism of p300 was shown to follow a ping-pong kinetic pathway and viscosity experiments revealed that product release and/or a conformational change were likely rate-limiting in catalysis. Detailed analysis of the p300 selective inhibitor Lys-CoA showed that it exhibited slow, tight-binding kinetics.
C1 Johns Hopkins Univ, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Cole, PA (reprint author), Johns Hopkins Univ, Dept Pharmacol & Mol Sci, 725 N Wolfe St, Baltimore, MD 21205 USA.
NR 51
TC 92
Z9 93
U1 0
U2 5
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 SEP 7
PY 2001
VL 276
IS 36
BP 33721
EP 33729
DI 10.1074/jbc.M104736200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 471CP
UT WOS:000170910200059
PM 11445580
ER

PT J
AU Aalfs, JD
   Narlikar, GJ
   Kingston, RE
AF Aalfs, JD
   Narlikar, GJ
   Kingston, RE
TI Functional differences between the human ATP-dependent nucleosome
   remodeling proteins BRG1 and SNF2H
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID YEAST SWI/SNF COMPLEX; HUMAN SWI-SNF; HISTONE OCTAMER;
   SACCHAROMYCES-CEREVISIAE; IN-VITRO; HO GENE; CHROMATIN; ISWI;
   TRANSCRIPTION; BINDING
AB ATP-dependent nucleosome remodeling complexes can be grouped into several classes that may differ in their biochemical remodeling activities and biological roles. Although there are a number of biochemical studies of each class of remodeler, there are very little data directly comparing the biochemical activities of remodelers from different classes. We have purified two ATP-hydrolyzing proteins, SNF2H and BRG1, which are members of complexes from two different classes of remodelers. Consistent with previous reports, these two homogeneous proteins can perform remodeling functions. We show significant functional differences between SNF2H and BRG1 in vitro; although both SNF2H and BRG1 hydrolyze ATP and remodel linear arrays of nucleosomes, only BRG1 can remodel mononucleosomes. Also, only BRG1 can alter the topology of nucleosomal plasmids. We propose that these functional differences reflect significant mechanistic differences between the two remodeler classes that will impact their biological roles.
C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
RP Kingston, RE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
NR 51
TC 60
Z9 61
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 SEP 7
PY 2001
VL 276
IS 36
BP 34270
EP 34278
DI 10.1074/jbc.M104163200
PG 9
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 471CP
UT WOS:000170910200130
PM 11435432
ER

PT J
AU Sharpless, NE
   Bardeesy, N
   Lee, KH
   Carrasco, D
   Castrillon, DH
   Aguirre, AJ
   Wu, EA
   Horner, JW
   DePinho, RA
AF Sharpless, NE
   Bardeesy, N
   Lee, KH
   Carrasco, D
   Castrillon, DH
   Aguirre, AJ
   Wu, EA
   Horner, JW
   DePinho, RA
TI Loss of p16(Ink4a) with retention of p19(Arf) predisposes mice to
   tumorigenesis
SO NATURE
LA English
DT Article
ID PLASMACYTOMA SUSCEPTIBILITY; TUMOR SUPPRESSION; G(1) CONTROL; INK4A
   LOCUS; MOUSE SKIN; IN-VIVO; IMMORTALIZATION; CELLS; GENE; FIBROBLASTS
AB The cyclin-dependent kinase inhibitor p16(INK4a) can induce senescence of human cells, and its loss by deletion, mutation or epigenetic silencing is among the most frequently observed molecular lesions in human cancer(1,2). Overlapping reading frames in the INK4A/ARF gene encode p16(INK4a) and a distinct tumour-suppressor protein, p19(ARF) (ref. 3). Here we describe the generation and characterization of a p16(Ink4a)-specific knockout mouse that retains normal p19(Arf) function. Mice lacking p16(Ink4a) were born with the expected mendelian distribution and exhibited normal development except for thymic hyperplasia. T cells deficient in p16(Ink4a) exhibited enhanced mitogenic responsiveness, consistent with the established role of p16(Ink4a) in constraining cellular proliferation. In contrast to mouse embryo fibroblasts (MEFs) deficient in p19(Arf) (ref. 4), p16(Ink4a)-null MEFs possessed normal growth characteristics and remained susceptible to Ras-induced senescence. Compared with wild-type MEFs, p16(Ink4a) null MEFs exhibited an increased rate of immortalization, although this rate was less than that observed previously for cells null for Ink4a/Arf, p19(Arf) or p53 (refs 4, 5). Furthermore, p16(Ink4a) deficiency was associated with an increased incidence of spontaneous and carcinogen-induced cancers. These data establish that p16(Ink4a), along with p19(Arf), functions as a tumour suppressor in mice.
C1 Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA.
NR 30
TC 501
Z9 513
U1 1
U2 14
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
J9 NATURE
JI Nature
PD SEP 6
PY 2001
VL 413
IS 6851
BP 86
EP 91
DI 10.1038/35092592
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 469EG
UT WOS:000170801200044
PM 11544531
ER

PT J
AU Chen, EY
   Nguyen, TD
AF Chen, EY
   Nguyen, TD
TI Gallbladder sludge
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
C1 Univ Washington, Seattle, WA 98195 USA.
   Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA.
RP Chen, EY (reprint author), Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC/NEJM
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD SEP 6
PY 2001
VL 345
IS 10
BP E2
EP E2
DI 10.1056/ENEJMicm010154
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 468RX
UT WOS:000170772900006
PM 11547762
ER

PT J
AU DeSalle, LM
   Latres, E
   Lin, D
   Graner, E
   Montagnoli, A
   Baker, RT
   Pagano, M
   Loda, M
AF DeSalle, LM
   Latres, E
   Lin, D
   Graner, E
   Montagnoli, A
   Baker, RT
   Pagano, M
   Loda, M
TI The de-ubiquitinating enzyme Unp interacts with the retinoblastoma
   protein
SO ONCOGENE
LA English
DT Article
DE Unp; retinoblastoma; isopeptidase; ubiquitin
ID FAT FACETS GENE; DEUBIQUITINATING ENZYME; MOUSE GENE; DEGRADATION;
   EXPRESSION; ENCODES; PROTOONCOGENE; ISOPEPTIDASE; PROTEASOME; SEQUENCES
AB The ubiquitin pathway is involved in the proteolytic turnover of many short-lived cellular regulatory proteins. Since selective degradation of substrates of this system requires the covalent attachment of a polyubiquitin chain to the substrates, degradation could be counteracted by de-ubiquitinating enzymes (or isopeptidases) which selectively remove the polyubiquitin chain. Unp is a human isopeptidase with still poorly understood biological functions. Here, we show that cellular Unp specifically interacts with the retinoblastoma gene product (pRb).
C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
   NYU, Med Ctr, Dept Pathol, New York, NY 10016 USA.
   NYU, Med Ctr, Caplan Comprehens Canc Ctr, New York, NY 10016 USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia.
RP Pagano, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
RI Graner, Edgard/K-4411-2012
FU NCI NIH HHS [5RO1-CA81755, P30-CA16087, R01-CA76584, R21-CA66229]; NIGMS
   NIH HHS [R01-GM57587]
NR 29
TC 26
Z9 31
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 0950-9232
J9 ONCOGENE
JI Oncogene
PD SEP 6
PY 2001
VL 20
IS 39
BP 5538
EP 5542
DI 10.1038/sj.onc.1204824
PG 5
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
   Heredity
GA 468WL
UT WOS:000170781100015
PM 11571652
ER

PT J
AU Blumenthal, D
   Gokhale, M
   Campbell, EG
   Weissman, JS
AF Blumenthal, D
   Gokhale, M
   Campbell, EG
   Weissman, JS
TI Preparedness for clinical practice - Reports of graduating residents at
   academic health centers
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID INTERNAL-MEDICINE; MANAGED CARE; EDUCATION; PHYSICIANS; FACULTY; VIEWS
AB Context Medical educators are seeking improved measures to assess the clinical competency of residents as they complete their graduate medical education.
   Objective To assess residents' perceptions of their preparedness to provide common clinical services during their last year of graduate medical education.
   Design, Setting, and Participants A 1998 national survey of residents completing their training in 8 specialties (internal medicine, pediatrics, family practice, obstetrics/gynecology, general surgery, orthopedic surgery, psychiatry, and anesthesiology) at academic health centers in the United States. A total of 2626 residents responded (response rate, 65%).
   Main Outcome Measures Residents' reports of their preparedness to perform clinical and nonclinical tasks relevant to their specialties.
   Results Residents in all specialties rated themselves as prepared to manage most of the common conditions they would encounter in their clinical career. However, more than 10% of residents in each specialty reported that they felt unprepared to undertake 1 or more tasks relevant to their disciplines, such as caring for patients with human immunodeficiency virus/acquired immunodeficiency syndrome or substance abuse (family practice) or nursing home patients (internal medicine); performance of spinal surgery (orthopedic surgery) or abdominal aortic aneurysm repair (general surgery); and management of chronic pain (anesthesiology).
   Conclusions Overall, residents in their last year of training at academic health centers rate their clinical preparedness as high. However, opportunities for improvement exist in preparing residents for clinical practice.
C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA.
   Partners Hlth Care Syst, Boston, MA USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
   Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor,Suite 901, Boston, MA 02114 USA.
NR 30
TC 124
Z9 125
U1 1
U2 6
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 SEP 5
PY 2001
VL 286
IS 9
BP 1027
EP 1034
DI 10.1001/jama.286.9.1027
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 469EW
UT WOS:000170802500015
PM 11559286
ER

PT J
AU Branch, WT
   Kern, D
   Haidet, P
   Weissmann, P
   Gracey, CF
   Mitchell, G
   Inui, T
AF Branch, WT
   Kern, D
   Haidet, P
   Weissmann, P
   Gracey, CF
   Mitchell, G
   Inui, T
TI Teaching the human dimensions of care in clinical settings
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID BEDSIDE CASE PRESENTATIONS; MEDICAL-STUDENTS; ROLE MODELS;
   PROFESSIONAL-DEVELOPMENT; RESIDENTS; EDUCATION; CURRICULUM; PHYSICIAN;
   PERCEPTIONS; EXPERIENCE
AB Despite repeated calls to emphasize the humanistic dimensions of care during medical education, these are few known techniques for effective teaching of humanism. We describe the barriers that inhibit humanistic teaching and suggest pragmatic teaching methods to overcome such barriers and teach humanistic care in clinical settings. We began by asking participants at a conference on patient-physician communications sponsored by the American Academy on Physician and Patient in June 1 1998, "What can we do in the patient's presence to improve and teach the human dimensions of care? Please provide one or more examples of approaches you found to be effective. " We augmented this information with suggestions from a number of colleagues in other settings. In a series of iterations, we analyzed all their suggestions to identify key teaching methods. We found that barriers to teaching humanism largely consist of elements of the informal and hidden curricula in medical schools. We then defined methods to help teachers overcome these barriers. Specific methods fall into the 3 categories of taking advantage of seminal events, role modeling, and using active learning skills. We believe that formal courses and other well-motivated endeavors that take place away from patients fall to foster humanistic care. In contrast, we present pragmatic teaching methods that can be used in the fast-paced setting of the clinical environment.
C1 Emory Univ, Sch Med, Dept Med, Div Gen Med, Atlanta, GA 30322 USA.
   Johns Hopkins Univ Sch, Bayview Med Ctr, Baltimore, MD USA.
   Baylor Coll Med, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA.
   Univ Minnesota, Sch Med, Fairview, MN USA.
   Univ Rochester, Sch Med, Dept Med, Rochester, NY USA.
   Indiana Univ, Sch Med, Indianapolis, IN USA.
   Fetzer Inst, Kalamazoo, MI USA.
RP Branch, WT (reprint author), Emory Univ, Sch Med, Dept Med, Div Gen Med, 1525 Clifton Rd, Atlanta, GA 30322 USA.
NR 56
TC 133
Z9 137
U1 0
U2 11
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 SEP 5
PY 2001
VL 286
IS 9
BP 1067
EP 1074
DI 10.1001/jama.286.9.1067
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 469EW
UT WOS:000170802500021
PM 11559292
ER

PT J
AU Mizuno, S
   Allemann, F
   Glowacki, J
AF Mizuno, S
   Allemann, F
   Glowacki, J
TI Effects of medium perfusion on matrix production by bovine chondrocytes
   in three-dimensional collagen sponges
SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH
LA English
DT Article
DE perfusion; 3D collagen sponge; in vitro; chondrocyte; tissue engineering
ID HUMAN DERMAL FIBROBLASTS; IN-VITRO; 3-DIMENSIONAL CULTURE; ELECTRICAL
   MIGRATION; DEMINERALIZED BONE; FLUID-FLOW; CARTILAGE; CELLS; GROWTH;
   CHONDROINDUCTION
AB Various culture systems have been used for examining the anabolic and catabolic functions of isolated chondrocytes as well as for tissue engineering purposes. Perfusion or frequent medium change is beneficial for three-dimensional (3D) cultures of many cell types. In this study, bovine articular chondrocytes (bACs) were grown in 3D collagen sponges with or without medium perfusion (0.33 mL/min) for up to 15 days. The influence of medium perfusion was evaluated using markers of cartilage matrix accumulation, synthesis, and gene expression. Metachromatic matrix, collagen type II, and hyaluronan accumulated around the cells within the collagen sponges. Sulfated glycosaminoglycans (S-GAGs) that accumulated in the sponge exposed to nonperfused control were 130% of that in the perfused sponge at day 7. S-GAG accumulation after 15 days in the nonperfused control was 230% more than at day 7 (p < 0.01). S-35-sulfate incorporation during the final 18 h of culture in the sponge exposed to nonperfusion was 180% greater than that in the perfused sponge (p < 0.01). Quantitative analyses show that at day 7, aggrecan and collagen type II gene expression were 350% and 240% greater, respectively, in the nonperfused culture than in the perfused one. These results indicate that perfused conditions that are beneficial for other cell types inhibit chondrogenesis by articular chondrocytes in 3D culture. (C) 2001 John Wiley & Sons, Inc.
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA USA.
RP Mizuno, S (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA.
FU NIAMS NIH HHS [AR44873, AR45793]
NR 35
TC 81
Z9 86
U1 1
U2 6
PU JOHN WILEY & SONS INC
PI NEW YORK
PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0021-9304
J9 J BIOMED MATER RES
JI J. Biomed. Mater. Res.
PD SEP 5
PY 2001
VL 56
IS 3
BP 368
EP 375
DI 10.1002/1097-4636(20010905)56:3<368::AID-JBM1105>3.0.CO;2-V
PG 8
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 442DV
UT WOS:000169270700007
PM 11372054
ER

PT J
AU Andriani, F
   Nan, B
   Yu, J
   Li, XY
   Weigel, NL
   McPhaul, MJ
   Kasper, S
   Kagawa, S
   Fang, BL
   Matusik, RJ
   Denner, L
   Marcelli, M
AF Andriani, F
   Nan, B
   Yu, J
   Li, XY
   Weigel, NL
   McPhaul, MJ
   Kasper, S
   Kagawa, S
   Fang, BL
   Matusik, RJ
   Denner, L
   Marcelli, M
TI Use of the probasin promoter ARR(2)PB to express Bax in androgen
   receptor-positive prostate cancer cells
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HUMAN ADENOVIRUS TYPE-5; PROAPOPTOTIC GENE BAX; TRANSCRIPTION
   ACTIVATION; INDUCED APOPTOSIS; BINDING DOMAIN; LNCAP CELLS; LINE LNCAP;
   IN-VIVO; CARCINOMA; CASPASE-7
AB Background: Adenovirus-mediated overexpression of the apoptosis-inducing protein Bax can induce apoptosis in prostate cancer cell lines. Constitutive overexpression of Bax could result in unwanted apoptosis in every site of accidental Bax accumulation in vivo. Therefore, we developed an adenoviral construct (Av-ARR(2)PB-Bax) in which the probasin promoter, modified to contain two androgen response elements, drives Bax expression. This promoter would be expected to limit expression of Bax to cells expressing the androgen receptor. Methods: A variety of androgen receptor (AR)-positive and -negative cell lines of prostatic or nonprostatic origin were infected with Av-ARR2PB-Bax or a control virus, Av-ARR(2)PB-CAT, in which the same promoter drives expression of the chloramphenicol acetyl transferase-reporter gene. Bax expression and apoptosis in vitro were assessed by western blot analysis. Tumor size and apoptosis in vivo were assessed after four weekly injections of Av-ARR(2)PB-Bax or Av-ARR(2)PB-CAT into subcutaneous LNCaP xenografts growing in uncastrated male mice. All statistical tests were two-sided. Results: Bax was overexpressed in an androgen-dependent way in AR-positive cell lines of prostatic origin but not in AR-positive cells of nonprostatic origin or in AR-negative cell lines of either prostatic or nonprostatic origin. The androgen dihydrotestosterone activated apoptosis in LNCaP cells infected with Av-ARR2PB-Bax but not in those infected with Av-ARR(2)-PB-CAT. Av-ARR(2)PB-Bax-injected LNCaP xenograft tumors decreased in tumor size from 34.1 mm(3) (95% confidence interval [CI] = 25.1 mm(3) to 43.1 mm(3)) to 24.6 mm(3) (95% CI = -2.5 mm(3) to 51.7 mm(3)), but the difference was not statistically significant (P = .5). Tumors injected with Av-ARR(2)PB-CAT increased in size, from 28.9 mm(3) (95% CI = 12.7 mm(3) to 45.1 mm(3)) to 206 mm(3) (95% CI = 122 mm(3) to 290 mm(3)) (P = .002) and contained statistically significant more apoptotic cells (23.3% [95% CI = 21.1% to 25.6%] versus 9.5% [95% CI = 8.0% to 11.1]) (P < .001). Conclusions: Av-ARR2PB-Bax induces androgen-dependent therapeutic apoptosis in vitro and in vivo by activating apoptosis in AR-positive cells derived specifically from prostatic epithelium and does not affect nonprostatic cells.
C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
   VA Med Ctr, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
   Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75230 USA.
   Vanderbilt Univ, Ctr Med, Dept Urol Surg, Nashville, TN 37232 USA.
   Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Cardiovasc Surg, Houston, TX 77030 USA.
   Texas Biotechnol Corp, Houston, TX USA.
RP Marcelli, M (reprint author), Baylor Coll Med, Dept Med, 2002 Holcombe,Bldg 109,Rm 217, Houston, TX 77030 USA.
RI KAGAWA, Shunsuke/B-2189-2011; Andriani, Francesca/D-4898-2017
OI Andriani, Francesca/0000-0002-6178-7789
FU NIDDK NIH HHS [R01DK03892, R01DK55748]
NR 43
TC 30
Z9 31
U1 0
U2 1
PU NATL CANCER INSTITUTE
PI BETHESDA
PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD SEP 5
PY 2001
VL 93
IS 17
BP 1314
EP 1324
DI 10.1093/jnci/93.17.1314
PG 11
WC Oncology
SC Oncology
GA 467ZU
UT WOS:000170734300010
PM 11535706
ER

PT J
AU Ma, J
   Giovannucci, E
   Pollak, M
   Chan, JM
   Gaziano, JM
   Willett, W
   Stampfer, MJ
AF Ma, J
   Giovannucci, E
   Pollak, M
   Chan, JM
   Gaziano, JM
   Willett, W
   Stampfer, MJ
TI Milk intake, circulating levels of insulin-like growth factor-I, and
   risk of colorectal cancer in men
SO JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID EPITHELIAL-CELL PROLIFERATION; PROMOTED COLON CARCINOGENESIS;
   IGF-BINDING-PROTEINS; FACTOR (IGF)-I; VITAMIN-D; CIGARETTE-SMOKING;
   FACTOR-ALPHA; DAIRY FOODS; DIETARY-FAT; CALCIUM
AB Background: Milk and dietary calcium may have antiproliferative effects against colorectal cancer, but milk intake also raises serum levels of insulinlike growth factor-I (IGF-I). A high ratio of IGF-I to IGF-binding protein-3 (IGFBP-3) has been linked to an increased risk of colorectal cancer. Methods: In a case-control study nested in the Physicians' Health Study, plasma samples were collected from the period 1982 through 1983 from 14 916 men, aged 40-84 years, who also answered dietary questionnaires. Circulating levels of IGF-I and IGFBP-3 were assayed among 193 men who developed colorectal cancer during 13 years of follow-up and 318 age- and smoking-matched cancer-free control men. Conditional logistic regression was used to assess relative risks (RRs) of colorectal cancer for tertiles of IGF-I/IGFBP-3 and dietary factors. Statistical tests were two-sided. Results: Overall, there was a moderate but statistically nonsignificant inverse association between intake of low-fat milk or calcium from dairy food and colorectal cancer risk. Intake of dairy food (especially low-fat milk) was also positively and moderately associated with plasma levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 among control men. We observed a statistically significant interaction between low-fat milk intake and IGF-I/IGFBP-3 in association with risk of colorectal cancer (P-interaction = .03). Nondrinkers with IGF-I/IGFBP-3 in the highest tertile had a threefold higher risk than nondrinkers with IGF-I/IGFBP-3 in the lowest tertile (RR = 3.05; 95% confidence interval [CI] = 1.29 to 7.24), but no such increase was seen among frequent low-fat milk drinkers (RR = 1.05; 95% CI = 0.41 to 2.69). Conversely, among men with high IGF-I/IGFBP-3, frequent low-fat milk drinkers had a 60% lower risk (95% CI = 0.17 to 0.87; P-trend = .02) than nondrinkers. Conclusion: Intake of dairy products was associated with a modest increase in circulating IGF-I levels, but intake of low-fat milk was associated with lower risk of colorectal cancer, particularly among individuals with high IGF-I/IGFBP-3. This subpopulation, which is at increased risk of colorectal cancer, might benefit the most from specific dietary intervention.
C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Publ Adm, Dept Nutr & Epidemiol, Boston, MA 02115 USA.
   Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ, Canada.
   Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Oncol, Montreal, PQ, Canada.
   McGill Univ, Montreal, PQ H3A 2T5, Canada.
   Univ Calif San Francisco, Dept Epidemiol & Biostat & Urol, San Francisco, CA 94143 USA.
   Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA.
   VA Boston Healthcare Syst, Moss Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
RP Ma, J (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 75 Francis St, Boston, MA 02115 USA.
RI Pollak, Michael/G-9094-2011
OI Pollak, Michael/0000-0003-3047-0604
FU NCI NIH HHS [CA40360, CA42182, CA78293]
NR 45
TC 108
Z9 111
U1 1
U2 8
PU NATL CANCER INSTITUTE
PI BETHESDA
PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0027-8874
J9 J NATL CANCER I
JI J. Natl. Cancer Inst.
PD SEP 5
PY 2001
VL 93
IS 17
BP 1330
EP 1336
DI 10.1093/jnci/93.17.1330
PG 7
WC Oncology
SC Oncology
GA 467ZU
UT WOS:000170734300012
PM 11535708
ER

PT J
AU Schneider, EC
   Leape, LL
   Weissman, JS
   Piana, RN
   Gatsonis, C
   Epstein, AM
AF Schneider, EC
   Leape, LL
   Weissman, JS
   Piana, RN
   Gatsonis, C
   Epstein, AM
TI Racial differences in cardiac revascularization rates: Does "overuse"
   explain higher rates among white patients?
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID BYPASS GRAFT-SURGERY; NEW-YORK-STATE; TRANSLUMINAL CORONARY ANGIOPLASTY;
   ARTERY DISEASE; CLUSTERED DATA; APPROPRIATENESS; ANGIOGRAPHY; UNDERUSE;
   ACCESS; RACE
AB Background: coronary artery bypass graft (CABG) surgery and percutaneous transluminal coronary angioplasty (PTCA) are well-established treatments for symptomatic coronary artery disease. Previous studies have documented racial differences in rates of use of these cardiac revascularization procedures. Other studies suggest that these procedures are overused: that is, they are done for patients with clinically inappropriate indications.
   Objective: To test the hypothesis that the higher rate of cardiac revascularization among white patients is associated with a higher prevalence of overuse (revascularization for clinically inappropriate indications) among white patients than among African-American patients.
   Design: Observational cohort study using Medicare claims and medical record review.
   Setting: 173 hospitals in five U.S. states.
   Participants: A stratified, weighted, random sample of 3960 Medicare beneficiaries who underwent coronary angiography during 1991 and 1992; 1692 of these patients underwent 1711 revascularization procedures within 90 days.
   Measurements: The proportion of CABG and PTCA procedures rated appropriate, uncertain, and inappropriate according to RAND criteria, and the multivariate odds of undergoing inappropriate revascularization among African-American patients and white patients.
   Results: After angiography, rates of PTCA (23% vs. 19%) and CABG surgery (29% vs. 17%) were significantly higher among white patients than among African-American patients. The respective rates of inappropriate PTCA and CABG surgery were 14% and 10%. Among the study states, rates of inappropriate use ranged from 4% to 24% for PTCA and 0% to 14% for CABG surgery. White patients were more likely than African-American patients to receive inappropriate PTCA (15% vs. 9%; different 6 percentage points [95% CI, -0.4 to 12.7 percentage points]), and difference by race was statistically significant among men (20% vs. 8%; difference, 12 percentage points [CI, 1.2 to 21.7 percentage points]). Rates of inappropriate CABG surgery did not differ by race (10% in both groups).
   Conclusions: Among a large and diverse sample of Medicare beneficiaries in five U.S. states, overuse of PTCA was greater among white men than among other groups, but this difference did not fully account for racial disparities in revascularization. Overuse of cardiac revascularization varied significantly by geographic region.
C1 Harvard Univ, Sch Publ Hlth, Brigham & Womens Hosp, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Brown Univ, Providence, RI 02912 USA.
RP Schneider, EC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA.
OI Schneider, Eric/0000-0002-1132-5084
FU AHRQ HHS [5-RO-HS07098-02S1]
NR 28
TC 106
Z9 106
U1 1
U2 1
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD SEP 4
PY 2001
VL 135
IS 5
BP 328
EP 337
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA 468WF
UT WOS:000170780600003
PM 11529696
ER

PT J
AU Kressin, NR
   Petersen, LA
AF Kressin, NR
   Petersen, LA
TI Racial differences in the use of invasive cardiovascular procedures:
   Review of the literature and prescription for future research
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Review
ID ACUTE MYOCARDIAL-INFARCTION; OF-VETERANS-AFFAIRS;
   CORONARY-REVASCULARIZATION PROCEDURES; ARTERY BYPASS-SURGERY;
   HEALTH-CARE SYSTEM; PATIENT-PHYSICIAN RELATIONSHIP;
   ISCHEMIC-HEART-DISEASE; CARDIAC PROCEDURES; ETHNIC-DIFFERENCES;
   DECISION-MAKING
AB Purpose: The cause of racial disparities in the use of invasive cardiac procedures remains unclear. To summarize, evaluate, and clarify gaps in the literature, studies examining racial differences in cardiac catheterization, percutaneous transluminal coronary angioplasty (PTCA), and coronary artery bypass grafting (CABG) were reviewed.
   Data Sources: MEDLINE search for English-language articles published from 1966 to May 2000.
   Study Selection: Empirical studies of adults.
   Data Extraction: The odds ratios for procedure use by race were examined for each study; cohorts and covariates were also documented.
   Data Synthesis: Literature was classified as one of three groups on the basis of study design. For the first group, which used administrative data, odds ratios (ORs) for African-American patients compared with white patients ranged from 0.41 to 0.94 for cardiac catheterization, from 0.32 to 0.80 for PTCA, and from 0.23 to 0.68 for CABG. Procedure rates were also lower for Hispanic and Asian patients. In the second group, which used detailed clinical data, African-American patients remained disproportionately less likely to receive cardiac catheterization (OR, 0.03 to 0.85), PTCA (OR, 0.20 to 0.87), and CABG (OR, 0.22 to 0.68). A few studies noted that Hispanic and Asian patients were also disproportionately less likely to receive such procedures. The third group used survey methods but found conflicting results regarding patient refusals as a source of racial variation. Less-educated patients and patients who were not as experienced with the procedure were more likely to decline PTCA. Physician bias was also associated with racial variation in recommendations for treatment.
   Conclusions: Racial differences in invasive cardiac procedure use were found even after adjustment for disease severity. Future studies should comprehensively and simultaneously examine the full range of patient, physician, and health care system variables related to racial differences in the provision of invasive cardiac procedures.
C1 Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA.
   Boston Univ, Sch Publ Hlth, Boston, MA USA.
   Houston Vet Affairs Med Ctr, Houston, TX USA.
   Baylor Coll Med, Houston, TX 77030 USA.
RP Kressin, NR (reprint author), Vet Affairs Med Ctr, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70 152, Bedford, MA 01730 USA.
NR 93
TC 269
Z9 269
U1 2
U2 5
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD SEP 4
PY 2001
VL 135
IS 5
BP 352
EP 366
PG 15
WC Medicine, General & Internal
SC General & Internal Medicine
GA 468WF
UT WOS:000170780600006
PM 11529699
ER

PT J
AU Molnar, G
   Dagher, MC
   Geiszt, M
   Settleman, J
   Ligeti, E
AF Molnar, G
   Dagher, MC
   Geiszt, M
   Settleman, J
   Ligeti, E
TI Role of prenylation in the interaction of Rho-family small GTPases with
   GTPase activating proteins
SO BIOCHEMISTRY
LA English
DT Article
ID NADPH OXIDASE; NUCLEOTIDE EXCHANGE; ALUMINUM FLUORIDE;
   CRYSTAL-STRUCTURE; ARACHIDONIC-ACID; BINDING PROTEINS; STRUCTURAL BASIS;
   RAS; COMPLEX; DOMAIN
AB The role of prenylation in the interaction of Rho-family small GTPases with their GTPase activating proteins (GAPs) was investigated. Prenylated and nonprenylated small GTPases were expressed in Sf9 insect cells and Escherichia coli. respectively. Nucleotide binding to and hydrolysis by prenylated and nonprenylated proteins were identical, but three major differences were observed in their reactions with GAPs. (1) Membrane-associated GAPs accelerate GTP hydrolysis only on prenylated Rac1 and RhoA, but they are inactive on the nonprenylated form of these proteins. The difference is independent of the presence of detergents. In contrast to Rac1 and RhoA, nonprenylated Cdc42 is able to interact with membrane-localized GAPs. (2) Full-length p50RhoGAP and p190RhoGAP react less intensely with nonprenylated Rac1 than with the prenylated protein, whereas no difference was observed in the reaction of isolated GAP domains of either p50RhoGAP or Bcr with the different types of Rac1. (3) Fluoride exerts a significant inhibitory effect only on the interaction of prenylated Rac1 with the isolated GAP domains of p50RhoGAP or Bet. The effect of fluoride is not influenced by addition or chelation of Al3+. This is the first detailed study demonstrating that prenylation of the small GTPase is an important factor in determining its reaction with GAPs. It is suggested that both intramolecular interactions and membrane targeting of GAP proteins represent potential mechanisms regulating Rac signaling.
C1 Semmelweis Univ, Dept Physiol, H-1444 Budapest, Hungary.
   CEA Grenoble, Lab DBMS BBSI, F-38054 Grenoble 9, France.
   Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA.
   Harvard Univ, Sch Med, Charlestown, MA USA.
RP Ligeti, E (reprint author), Semmelweis Univ, Dept Physiol, POB 259, H-1444 Budapest, Hungary.
EM Ligeti@puskin.sote.hu
NR 46
TC 48
Z9 48
U1 0
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD SEP 4
PY 2001
VL 40
IS 35
BP 10542
EP 10549
DI 10.1021/bi011158e
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 467YT
UT WOS:000170731900015
PM 11523996
ER

PT J
AU Bateman, J
   Reddy, RS
   Saito, H
   Van Vactor, D
AF Bateman, J
   Reddy, RS
   Saito, H
   Van Vactor, D
TI The receptor tyrosine phosphatase Dlar and integrins organize actin
   filaments in the Drosophila follicular epithelium
SO CURRENT BIOLOGY
LA English
DT Article
ID MOTOR AXON GUIDANCE; CELL POLARITY; OVARIAN FOLLICLES; PS2 INTEGRIN;
   GERM-LINE; PROTEIN; LAMININ; MORPHOGENESIS; MICROFILAMENT; OOGENESIS
AB Background: Regulation of actin structures is instrumental in maintaining proper cytoarchitecture in many tissues. In the follicular epithelium of Drosophila ovaries, a system of actin filaments is coordinated across the basal surface of cells encircling the oocyte. These filaments have been postulated to regulate oocyte elongation; however, the molecular components that control this cytoskeletal array are not yet understood.
   Results: We find that the receptor tyrosine phosphatase (RPTP) Dlar and integrins are involved in organizing basal actin filaments in follicle cells. Mutations in Dlar and the common beta -integrin subunit mys cause a failure in oocyte elongation, which is correlated with a loss of proper actin filament organization. Immunolocalization shows that early in oogenesis Dlar is polarized to membranes where filaments terminate but becomes generally distributed late in development, at which time beta -integrin and Enabled specifically associate with actin filament terminals. Rescue experiments point to the early period of polar Dlar localization as critical for its function. Furthermore, clonal analysis shows that loss of Dlar or mys influences actin filament polarity in wild-type cells that surround mutant tissues, suggesting that communication between neighboring cells regulates cytoskeletal organization. Finally, we find that two integrin a subunits encoded by mew and if are required for proper oocyte elongation, implying that multiple components of the ECM are instructive in coordinating actin fiber polarity.
   Conclusions: Dlar cooperates with integrins to coordinate actin filaments at the basal surface of the follicular epithelium. To our knowledge, this is the first direct demonstration of an RPTP's influence on the actin cytoskeleton.
C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Canc, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Van Vactor, D (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
FU NIGMS NIH HHS [GM53415]; NINDS NIH HHS [NS35909, NS40043]
NR 53
TC 77
Z9 77
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA
SN 0960-9822
J9 CURR BIOL
JI Curr. Biol.
PD SEP 4
PY 2001
VL 11
IS 17
BP 1317
EP 1327
DI 10.1016/S0960-9822(01)00420-1
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 469WN
UT WOS:000170839200017
PM 11553324
ER

PT J
AU Gibbons, D
   Douglas, NC
   Barber, DF
   Liu, Q
   Sullo, R
   Geng, LP
   Fehling, HJ
   von Boehmer, H
   Hayday, AC
AF Gibbons, D
   Douglas, NC
   Barber, DF
   Liu, Q
   Sullo, R
   Geng, LP
   Fehling, HJ
   von Boehmer, H
   Hayday, AC
TI The biological activity of natural and mutant pT alpha alleles
SO JOURNAL OF EXPERIMENTAL MEDICINE
LA English
DT Article
DE pre-TCR; thymocyte development; alpha/beta T cells; allelic exlusion;
   transgenic
ID T-CELL-RECEPTOR; BETA-CHAIN; THYMOCYTE DEVELOPMENT; IN-VIVO; EXPRESSION;
   DOMAIN; GENE; EXCLUSION; SURFACE; LOCUS
AB beta selection is a major checkpoint in early thymocyte differentiation, mediated by successful expression of the pre-T cell receptor (TCR) comprising the TCR beta chain, CD3 proteins, and a surrogate TCR alpha chain, pT alpha. The mechanism of action of the pre-TCR is unresolved. In humans and mice, the pT alpha gene encodes two RNAs, pT alpha (a), and a substantially truncated form, pT alpha (b). This study shows that both are biologically active in their capacity to rescue multiple thymocyte defects in pT alpha (-/-) mice. Further active alleles of pT alpha include one that lacks both the major ectodomain and much of the long cytoplasmic tail (which is unique among antigen receptor chains), and another in which the cytoplasmic tail is substituted with the short tail of TCR C alpha. Thus, very little of the pT alpha chain is required for function. These data support a hypothesis that the primary role of pT alpha is to stabilize the pre-TCR, and that much of the conserved structure of pT alpha probably plays a critical regulatory role.
C1 Univ London Kings Coll, Guys Hosp, GKT Sch Med, Peter Gorer Dept Immunobiol, London SE1 9RT, England.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Univ Clin Ulm, Fac Med, Dept Immunol, D-89070 Ulm, Germany.
   Yale Univ, Dept Mol Cell & Dev Biol, New Haven, CT 06520 USA.
RP Hayday, AC (reprint author), Univ London Kings Coll, Guys Hosp, GKT Sch Med, Peter Gorer Dept Immunobiol, 3rd Floor New Guys House, London SE1 9RT, England.
EM adrian.hayday@kcl.ac.uk
RI Barber, Domingo/G-1257-2010
OI Barber, Domingo/0000-0001-8824-5405
FU NIGMS NIH HHS [GM37759]
NR 39
TC 25
Z9 25
U1 0
U2 0
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA
SN 0022-1007
J9 J EXP MED
JI J. Exp. Med.
PD SEP 3
PY 2001
VL 194
IS 5
BP 695
EP 703
DI 10.1084/jem.194.5.695
PG 9
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA 470LP
UT WOS:000170873700016
PM 11535637
ER

PT J
AU Branas, CC
   Knudson, MM
AF Branas, CC
   Knudson, MM
TI Helmet laws and motorcycle rider death rates
SO ACCIDENT ANALYSIS AND PREVENTION
LA English
DT Article
DE injury; motor vehicles; motorcycle helmets; health policy
ID ALCOHOL-USE; INJURIES; HEAD; SAFETY; FATALITIES; SEVERITY; DRIVERS;
   CRASHES; COSTS; TEXAS
AB We investigated motorcycle rider death rates between states with full motorcycle helmet laws and those without. This was done using both unadjusted bivariate analyses and multivariate random-effects generalized least squares regression models of rider death rates. Multivariate models were adjusted for the competing influences of several explanatory variables, including the existence of a motorcycle helmet law. From 1994 to 1996, states with helmet laws experienced a median death rate of 6.20 riders per 10000 registered motorcycles and states without helmet laws experienced a median death rate of 5.07 riders per 10000 registered motorcycles (P = 0.008). After controlling for other factors that affect motorcycle rider fatalities (most notably population density and temperature), death rates in states with full helmet laws were shown to be lower on average than deaths rates in states without full helmet laws (P = 0.740). Our study weakens the claim that rider death rates are significantly lower in states without full motorcycle helmet laws. (C) 2001 Elsevier Science Ltd. All rights reserved.
C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
   Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
   Univ Calif San Francisco, San Francisco Gen Hosp, Dept Surg, San Francisco, CA 94110 USA.
RP Branas, CC (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, 807 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
FU PHS HHS [R49CCR903697]
NR 30
TC 52
Z9 52
U1 0
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0001-4575
J9 ACCIDENT ANAL PREV
JI Accid. Anal. Prev.
PD SEP
PY 2001
VL 33
IS 5
BP 641
EP 648
DI 10.1016/S0001-4575(00)00078-6
PG 8
WC Ergonomics; Public, Environmental & Occupational Health; Social
   Sciences, Interdisciplinary; Transportation
SC Engineering; Public, Environmental & Occupational Health; Social
   Sciences - Other Topics; Transportation
GA 457HD
UT WOS:000170130300007
PM 11491244
ER

PT J
AU Tondo, L
   Hennen, J
   Baldessarini, RJ
AF Tondo, L
   Hennen, J
   Baldessarini, RJ
TI Lower suicide risk with long-term lithium treatment in major affective
   illness: a meta-analysis
SO ACTA PSYCHIATRICA SCANDINAVICA
LA English
DT Review
DE bipolar disorder; depression; lithium; mania; meta-analysis; suicide;
   treatment
ID MANIC-DEPRESSIVE ILLNESS; MAINTENANCE TREATMENT; BIPOLAR DISORDER;
   PROPHYLACTIC LITHIUM; MOOD DISORDERS; MORTALITY; POPULATION; BEHAVIOR;
   DISCONTINUATION; ANTIDEPRESSANTS
AB Objective: To compare suicide rates with vs. without long-term lithium treatment in major affective disorders.
   Method: Broad searching yielded 22 studies providing suicide rates during lithium maintenance, 13 also provide rates without such treatment. Study quality was scored, between-study variance tested, and suicide rates on vs. off lithium examined by meta-analyses using random-effects regression methods to model risk ratios.
   Results: Among 5647 patients (33 473 patient-years of risk) in 22 studies, suicide was 82% less frequent during lithium-treatment (0.159 vs. 0.875 deaths/100 patient-years). The computed risk-ratio in studies with rates on/off lithium was 8.85 (95% CI, 4.12-19.1; P < 0.0001). Higher rates off-lithium were not accounted for by treatment-discontinuation.
   Conclusion: Suicide risk was consistently lower during long-term treatment of major affective illnesses with lithium in all studies in the meta-analysis, including the few involving treatment-randomization.
C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorders Res, Bipolar & Psychot Disorders Program, Belmont, MA USA.
   Univ Cagliari, Ctr Lucio Bini, Stanley Fdn, Res Ctr, Sardinia, Italy.
   Univ Cagliari, Dept Psychol, Sardinia, Italy.
RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA.
FU NIMH NIH HHS [MH-47370]
NR 74
TC 138
Z9 140
U1 0
U2 3
PU MUNKSGAARD INT PUBL LTD
PI COPENHAGEN
PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK
SN 0001-690X
J9 ACTA PSYCHIAT SCAND
JI Acta Psychiatr. Scand.
PD SEP
PY 2001
VL 104
IS 3
BP 163
EP 172
DI 10.1034/j.1600-0447.2001.00464.x
PG 10
WC Psychiatry
SC Psychiatry
GA 466BZ
UT WOS:000170625600002
PM 11531653
ER

PT J
AU Libet, JM
   Frueh, BC
   Pellegrin, KL
   Gold, PB
   Santos, AB
   Arana, GW
AF Libet, JM
   Frueh, BC
   Pellegrin, KL
   Gold, PB
   Santos, AB
   Arana, GW
TI Absenteeism and productivity among mental health employees
SO ADMINISTRATION AND POLICY IN MENTAL HEALTH
LA English
DT Article
DE absenteeism; employees; sick leave
AB We examined archival data to test the hypothesis that absenteeism is inversely related to work productivity among mental health employees at a Veterans Affairs Medical Center outpatient clinic. Results provided partial support for this hypothesis in that there was an inverse correlation between one measure of productivity and the percentage of sick and family care leave taken on Mondays and Fridays (r=.54). No significant relationship between work productivity and total sick and/or family care leave was found, although there was a trend in that direction (r=.34). These data suggest that mental health clinicians who use high levels of sick and/or family care leave are not necessarily unproductive workers. However, high percentages of absenteeism. on Mondays and Fridays may represent a red flag for identifying under-performing clinicians. Examination of absenteeism patterns may prove useful for administrators. Management policy strategies to reduce absenteeism are suggested.
C1 Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA.
   Med Univ S Carolina, Dept Psychiat & Behav Sci, Columbia, SC 29208 USA.
RP Libet, JM (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA.
FU NIMH NIH HHS [K08-MH01660-01]
NR 9
TC 3
Z9 3
U1 0
U2 1
PU KLUWER ACADEMIC-HUMAN SCIENCES PRESS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA
SN 0894-587X
J9 ADM POLICY MENT HLTH
JI Adm. Policy. Ment. Health
PD SEP
PY 2001
VL 29
IS 1
BP 41
EP 50
DI 10.1023/A:1013116931570
PG 10
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA 512LJ
UT WOS:000173325600003
PM 11811772
ER

PT J
AU Sarr, AD
   Lu, YC
   Sankale, JL
   Eisen, G
   Popper, S
   Mboup, S
   Kanki, PJ
   Cao, HY
AF Sarr, AD
   Lu, YC
   Sankale, JL
   Eisen, G
   Popper, S
   Mboup, S
   Kanki, PJ
   Cao, HY
TI Robust HIV type 2 cellular immune response measured by a modified
   anthrax toxin-based enzyme-linked immunospot assay
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID CYTOTOXIC T-CELLS; PROTECTIVE ANTIGEN; MEDIATED DELIVERY; PEPTIDE
   ANTIGENS; IN-VITRO; VIRUS; INFECTION; LYMPHOCYTES; EPITOPE; PROTEIN
AB Evaluation of immune mechanisms responsible for control of viral replication is critical to understanding HIV-2 attenuated biological characteristics in pathogenesis and transmission. Evaluation of the cellular immune response is often based on labor-intensive techniques that limit the scope of most studies performed. A simple and rapid anthrax toxin-based ELISPOT method to assess HIV-2 cellular immune response was developed. The modified anthrax toxin-based antigen presentation process performed better than a recombinant vaccinia system and the ELISPOT method significantly enhanced the ease and simplicity of the assay. Using this method, a robust HIV-2 cellular immune response directed toward the p26 core protein was exhibited in 21 of 24 (87.5%) infected women, and all 8 seronegative subjects were negative in both assays. Cellular immune responses were associated with low HIV-2 viral load. This simple and rapid modified anthrax toxin-based ELISPOT method allowed us to demonstrate, strong cellular immune responses that may be critical determinants in the HIV-2 attenuated phenotype.
C1 Harvard Univ, Sch Publ Hlth, Harvard AIDS Inst, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
   CheiKh Anta Diop Univ, Dept Bacteriol & Virol, Dakar, Senegal.
   Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Calif Dept Hlth Serv, Berkeley, CA 94704 USA.
RP Kanki, PJ (reprint author), Harvard Univ, Sch Publ Hlth, Harvard AIDS Inst, Dept Immunol & Infect Dis, 651 Huntington Ave, Boston, MA 02115 USA.
FU FIC NIH HHS [5D43 TW00004]; PHS HHS [A1 46274, A1 43754]
NR 38
TC 7
Z9 7
U1 0
U2 1
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 0889-2229
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD SEP
PY 2001
VL 17
IS 13
BP 1257
EP 1264
DI 10.1089/088922201750461311
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 471HN
UT WOS:000170923900005
PM 11559425
ER

PT J
AU Reoux, JP
   Saxon, AJ
   Malte, CA
   Baer, JS
   Sloan, KL
AF Reoux, JP
   Saxon, AJ
   Malte, CA
   Baer, JS
   Sloan, KL
TI Divalproex sodium in alcohol withdrawal: A randomized double-blind
   placebo-controlled clinical trial
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the Research-Society-on-Alcoholism
CY JUN 26-JUL 01, 1999
CL SANTA BARBARA, CALIFORNIA
SP Res Soc Alcoholism
DE alcoholism; substance withdrawal; valproic acid
ID VALPROIC ACID; BENZODIAZEPINES; CARBAMAZEPINE; ANTICONVULSANTS;
   DISORDERS; TOXICITY; OXAZEPAM
AB Background: Divalproex sodium, an anticonvulsant and antikindling agent and gamma -aminobutyric acid enhancer, has been proposed as an alternative to benzodiazepines for treating alcohol withdrawal. This study reports on a randomized, double-blind, placebo-controlled trial of divalproex sodium in acute alcohol withdrawal.
   Methods: Thirty-six hospitalized patients experiencing moderate alcohol withdrawal as measured by a score of at least 10 on the revised Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWA-Ar) were randomized to receive either divalproex sodium 500 mg three times per day for 7 days or matched placebo in a double-blind manner. All subjects received a baseline dose of oxazepam. and had additional oxazepam available as a rescue medication in accordance with a standard, symptom-triggered detoxification protocol. Mean total milligrams of oxazepam received, progression of withdrawal symptoms, psychological distress as measured by the Symptom Checklist-90, side effects, and adverse outcomes were compared between groups.
   Results: Use of divalproex sodium resulted in less use of oxazepam (p < 0.033). Group differences seemed primarily driven by those subjects who experienced symptoms above threshold level (CIWA-Ar <greater than or equal to>10) after 12 hr. The progression in severity of withdrawal symptoms (increase in CIWA-Ar above baseline) was also significantly greater in the placebo group (p < 0.05).
   Conclusions: This placebo-controlled pilot study suggests that divalproex sodium significantly affects the course of acute alcohol withdrawal and reduces the need for treatment with a benzodiazepine. A more aggressive loading dose strategy may demonstrate a more robust or earlier response.
C1 VA Puget Sound Hlth Care Syst, Addict Treatment Ctr 116ATC, Seattle, WA 98108 USA.
   Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA.
RP Reoux, JP (reprint author), VA Puget Sound Hlth Care Syst, Addict Treatment Ctr 116ATC, 1660 S Columbin Way, Seattle, WA 98108 USA.
NR 26
TC 63
Z9 64
U1 1
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 SEP
PY 2001
VL 25
IS 9
BP 1324
EP 1329
DI 10.1111/j.1530-0277.2001.tb02354.x
PG 6
WC Substance Abuse
SC Substance Abuse
GA 473LE
UT WOS:000171044800012
PM 11584152
ER

PT J
AU Myrick, H
   Henderson, S
   Anton, RF
AF Myrick, H
   Henderson, S
   Anton, RF
TI Utility of a new assay for carbohydrate-deficient transferrin (BIORAD
   %CDT TIA) to monitor abstinence during a treatment outcome study
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE alcoholism; transferrin; gamma-glutamyltransferase; treatment outcome
ID GAMMA-GLUTAMYL-TRANSFERASE; ALCOHOL-CONSUMPTION; LABORATORY MARKERS;
   DETECTING RELAPSE; DRINKING; SERUM; ABUSE; TRANSPLANTATION;
   TRANSPEPTIDASE; ETHANOL
AB Background: The ability to reliably detect heavy alcohol use is important in both clinical and research populations. The current study evaluates the utility of the newest method of measuring carbohydrate deficient transferrin (CDT) in monitoring the abstinence during a treatment outcome study.
   Methods: Blood from 40 alcohol dependent individuals was obtained at baseline and at weeks 4, 8, and 12 of treatment. Differences in percent of baseline GGT and %CDT levels were analyzed in people who remained abstinent throughout treatment (abstainers) and in those who consumed alcohol during treatment (drinkers).
   Results: There was a significant decrease in the percent of baseline %CDT levels in the subjects who abstained at week 4 and a trend at weeks 8 and 12. Conversely, there were no significant differences in percent of baseline GGT levels between drinkers and abstainers at any time point.
   Conclusions: Although small in nature, this study provides preliminary evidence for the use of the relatively new Biorad %CDT assay to monitor drinking status during treatment outcome studies. This study is also consistent with previously reported findings that GGT appears to be less sensitive than %CDT in detecting the consumption of alcohol. A larger trial focusing on sex differences in the utility of % CDT to monitor outcome would be of interest.
C1 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA.
   Med Univ S Carolina, Alcohol Res Ctr, Charleston, SC 29425 USA.
RP Myrick, H (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA.
FU NIAAA NIH HHS [K23 AA00314-01]
NR 24
TC 9
Z9 14
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 SEP
PY 2001
VL 25
IS 9
BP 1330
EP 1334
DI 10.1111/j.1530-0277.2001.tb02355.x
PG 5
WC Substance Abuse
SC Substance Abuse
GA 473LE
UT WOS:000171044800013
PM 11584153
ER

PT J
AU Kessova, IG
   Leo, MA
   Lieber, CS
AF Kessova, IG
   Leo, MA
   Lieber, CS
TI Effect of beta-carotene on hepatic cytochrome P-450 in ethanol-fed rats
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE beta-carotene; ethanol; cytochrome p-450; liver; microsomes
ID LUNG-CANCER; ALCOHOL; ALPHA; LIVER; HEPATOTOXICITY; HYDROXYLATION;
   ANTIOXIDANT; NITROPHENOL; MICROSOMES; CYP2E1
AB Background: Hepatotoxicity of ethanol is increased by beta -carotene in both rodents and nonhuman primates. Furthermore, in smokers who are also drinkers, beta -carotene increases the incidence of pulmonary cancer. The hepatotoxicity was associated with proliferation of the membranes of the smooth endoplasmic reticulum, suggesting the involvement of cytochromes P-450. Therefore, the aim of the present study was to assess the effect of beta -carotene and ethanol treatment on rodent hepatic cytochromes P-450.
   Methods and Results: Weanling male Sprague-Dawley rats were pair-fed beta -carotene (56.5 mg/l of diet) for 8 weeks, with and without ethanol (Lieber-DeCarli, 1994 liquid diet). As expected, ethanol increased CYP2E1 (measured by Western blots) from 67 +/- 8 to 317 +/- 27 densitometric units (p < 0.001). Furthermore, <beta>-carotene potentiated the ethanol induction to 442 +/- 38 densitometric units (p < 0.01) with a significant interaction (p = 0.012). The rise was confirmed by a corresponding increase in the hydroxylation of p-nitrophenol, a specific substrate for CYP2E1, and by the inhibition with diethyl dithiocarbamate (50 <mu>M). beta -Carotene alone also significantly induced CYP4A1 protein (328 +/- 49 vs. 158 +/- 17 densitometric units, p < 0.05). The corresponding CYP4A1 mRNA (measured by Northern blots) was also increased (p < 0.05) and there was a significant interaction of the two treatments (p = 0.015). The combination of ethanol and beta -carotene had no significant effect on either total cytochrome P-450 or CYP1A1/2, CYP2B, CYP3A, and CYP4A2/3 contents.
   Conclusions: beta -Carotene potentiates the CYP2E1 induction by ethanol in rat liver and also increases CYP4A1, which may, at least in part, explain the associated hepatotoxicity.
C1 Bronx Vet Adm Med Ctr, Ctr Alcohol Res & Treatment, Bronx, NY 10468 USA.
   Mt Sinai Sch Med, New York, NY USA.
RP Lieber, CS (reprint author), Bronx Vet Adm Med Ctr, Ctr Alcohol Res & Treatment, 130 W Kingsbridge Rd, Bronx, NY 10468 USA.
FU NIAAA NIH HHS [AA07275, AA11160]
NR 24
TC 10
Z9 10
U1 0
U2 1
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 SEP
PY 2001
VL 25
IS 9
BP 1368
EP 1372
DI 10.1111/j.1530-0277.2001.tb02360.x
PG 5
WC Substance Abuse
SC Substance Abuse
GA 473LE
UT WOS:000171044800018
PM 11584158
ER

PT J
AU Ferris, TG
   Crain, EF
   Oken, EM
   Wang, L
   Clark, S
   Camargo, CA
AF Ferris, TG
   Crain, EF
   Oken, EM
   Wang, L
   Clark, S
   Camargo, CA
CA MARC Investigators
TI Insurance and quality of care for children with acute asthma
SO AMBULATORY PEDIATRICS
LA English
DT Article
DE asthma; children; emergency department; insurance; managed care;
   Medicaid; primary care; quality; uninsured
ID HEALTH MAINTENANCE ORGANIZATION; MANAGEMENT-PRACTICES; RISK;
   HOSPITALIZATION; EMERGENCY; MEDICAID; ADULTS; ACCESS
AB Background- Increasing attention has been paid to the role of insurance in determining quality and outcomes of care. Pressures to reduce health costs and to improve quality have prompted attempts by managed care organizations to decrease the use of the emergency department (ED) for acute asthma, but performance comparisons between insurance types remain rare.
   Methods.-We used prospective data from the; Multicenter Airway Research Collaboration on 965 children with acute asthma presenting to 36 EDs. We compared measures of quality of pre-ED care, acute severity and short-term outcomes (length of stay, percent relapse, and percent with ongoing symptoms) across 4 different insurance categories: managed care, indemnity, Medicaid, and uninsured. We used multivariate regression to control for differences in education, estimated income, race/ethnicity, and chronic asthma: severity and acute asthma characteristics.
   Results.-Children with managed care and indemnity had similar demographic and asthma characteristics, but these children differed significantly from Medicaid and uninsured patients. Managed care and indemnity insured children had similar ratings on all 7 quality measures, with Medicaid and uninsured children ranking significantly lower on most measures, including (1) percent with primary care provider (PCP) (P < .001), (2) percent using ED as usual site of asthma care (P < .001), (3) percent using ED for prescriptions (P < .001), (4) percent with a ratio of >1 of ED visits to acute office visits within the past year (P =.003). and (5) percent visiting their PCP within the week prior to ED visit (P < .001). Children with managed care were more acutely ill than: were indemnity, Medicaid, or uninsured children on presentation to the ED (pulmonary index of 4.6, 4.0, 4.2, and 3.9, respectively, P =.007). There were no significant differences in length of hospital stay, relapse, and ongoing exacerbation.
   Conclusions.-Our results indicate similar quality of care, greater severity of acute asthma, and no worse outcomes for children with managed care compared to children with indemnity insurance. We found uninsured children to have consistently poorer quality of care than insured patients.
C1 Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, MARC Coordinating Ctr,Sch Med, Boston, MA 02114 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med,Med & Pediat Serv, Inst Hlth Policy,Ctr Child & Adolescent Hlth Poli, Boston, MA 02114 USA.
   Albert Einstein Coll Med, Jacobi Med Ctr, Dept Pediat, Div Emergency Med, Bronx, NY 10467 USA.
   Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA.
RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Emergency Med, MARC Coordinating Ctr,Sch Med, Clin Bldg 397,55 Fruit St, Boston, MA 02114 USA.
FU NHLBI NIH HHS [HL-03533, HL-63253]
NR 30
TC 28
Z9 28
U1 2
U2 4
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 SEP-OCT
PY 2001
VL 1
IS 5
BP 267
EP 274
DI 10.1367/1539-4409(2001)001<0267:IAQOCF>2.0.CO;2
PG 8
WC Pediatrics
SC Pediatrics
GA 501HE
UT WOS:000172678600008
PM 11888414
ER

PT J
AU Sabatine, MS
   Januzzi, JL
   Snapinn, S
   Theroux, P
   Jang, IK
AF Sabatine, MS
   Januzzi, JL
   Snapinn, S
   Theroux, P
   Jang, IK
TI A risk score system for predicting adverse outcomes and magnitude of
   benefit with glycoprotein IIb/IIIa inhibitor therapy in patients with
   unstable angina pectoris
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; ST-SEGMENT
   ELEVATION; INTERNATIONAL TRIAL; III REGISTRY; STRATIFICATION;
   ELECTROCARDIOGRAM; THROMBOLYSIS; PROGNOSIS; DEATH
AB Clinical outcomes of patients with unstable angina are variable. We sought to identify predictors of adverse clinical outcomes in patients with unstable angina and to investigate whether these factors would predict the magnitude of benefit achieved with platelet glycoprotein Ilb/IIIa inhibition. We analyzed 20 variables in the 1,915 patients enrolled in the Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. Five independent predictors were identified: age > 65 years, prior coronary artery bypass grafting, antecedent aspirin use, antecedent beta -blocker use, and ST depressions on the presenting electrocardiogram. A risk score system was created using these predictors in which patients were assigned 1 point for the presence of each risk factor. There was a progressive increase in the rate of the composite end point of death, myocardial infarction, or refractory ischemia at 7 days with an increasing number of risk factors. For patients treated with heparin alone, the composite end point event rate was 6.5% in the group with 0 or 1 predictor, 14.6% in the group with 2 predictors, 22.7% in the group with 3 predictors, and 37.1% in the group with 4 or 5 predictors (p < 0.00001). When dividing patients into low- (0 or 1 point), medium(2 or 3 points), and high-risk (4 or 5 points) groups, the addition of tirofiban to heparin therapy was associated with no significant benefit in the low-risk group, a 5.2% absolute reduction in the medium-risk group (p = 0.05), and a 16% absolute reduction in the high-risk group (p = 0.0055). Thus, we have developed a risk score system using 5 variables that can be used to identify patients at high risk for death and cardiac ischemic events and who experience the greatest benefit from the addition of a glycoprotein IIb/IIIa inhibitor to their treatment regimen. (C) 2001 by Excerpta Medica, Inc.
C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02114 USA.
   Merck Res Labs, W Point, PA USA.
   Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA.
NR 21
TC 15
Z9 15
U1 0
U2 0
PU EXCERPTA MEDICA INC
PI NEW YORK
PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA
SN 0002-9149
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD SEP 1
PY 2001
VL 88
IS 5
BP 488
EP 492
DI 10.1016/S0002-9149(01)01724-6
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 466NV
UT WOS:000170652400005
PM 11524055
ER

PT J
AU Mulsant, BH
   Pollock, BG
   Nebes, R
   Miller, MD
   Sweet, RA
   Stack, J
   Houck, PR
   Bensasi, S
   Mazumdar, S
   Reynolds, CF
AF Mulsant, BH
   Pollock, BG
   Nebes, R
   Miller, MD
   Sweet, RA
   Stack, J
   Houck, PR
   Bensasi, S
   Mazumdar, S
   Reynolds, CF
TI A twelve-week, double-blind, randomized comparison of nortriptyline and
   paroxetine in older depressed inpatients and outpatients
SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY
LA English
DT Article; Proceedings Paper
CT 40th Annual Meeting of the New-Clinical-Drug-Evaluation-Unit
CY MAY 30-JUN 02, 2000
CL BOCA RATON, FL
SP New Clin Drug Evaluat Unit
ID SEROTONIN REUPTAKE INHIBITORS; ISCHEMIC-HEART-DISEASE; LATE-LIFE
   DEPRESSION; MAJOR DEPRESSION; ELDERLY-PATIENTS; CONTROLLED MULTICENTER;
   COMPARATIVE EFFICACY; CLINICAL-RESPONSE; RATING-SCALE; ANTIDEPRESSANTS
AB Selective serotonin reuptake inhibitors may be less efficacious than tricyclic antidepressants in the treatment of severe depression in older patients. The authors compared the 12-week clinical outcome of older depressed patients treated with nortriptyline or paroxetine in a double-blind randomized comparison in 116 psychiatric inpatients and outpatients (mean age: 72 +/-8 years) who presented with a major depressive episode or melancholic depression. Discontinuation and response rates were compared inpatients who began or who completed treatment. The discontinuation rate due to side effects was significantly higher with nortriptyline than with paroxetine (33% Vs. 16%). There were no significant differences between the rates of response in the Intent-to-Treat analysis (nortriptyline: 57% vs. paroxetine: 55%), or the Completer analysis (nortriptyline: 78% vs. paroxetine: 84%). Altbough paroxetine appears to be better tolerated than nortriptyline, the efficacy of these two drugs does not appear to differ in the acute treatment of older depressed patients, including hospitalized patients and those with melancholic features.
C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Intervent Res Ctr Study Latelife Mood Disorders, Pittsburgh, PA 15260 USA.
   VA Pittsburgh Hlth Care Syst, Educ & Clin Ctr, Pittsburgh, PA USA.
RP Mulsant, BH (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin E837, 3811 Ohara St, Pittsburgh, PA 15213 USA.
EM mulsantbh@msx.upmc.edu
FU NIA NIH HHS [AG 05133]; NIMH NIH HHS [MH 01509, MH 00295, MH 01613, MH
   37869, MH 52247, MH43832]
NR 45
TC 70
Z9 71
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1064-7481
EI 1545-7214
J9 AM J GERIAT PSYCHIAT
JI Am. J. Geriatr. Psychiatr.
PD FAL
PY 2001
VL 9
IS 4
BP 406
EP 414
DI 10.1176/appi.ajgp.9.4.406
PG 9
WC Geriatrics & Gerontology; Gerontology; Psychiatry
SC Geriatrics & Gerontology; Psychiatry
GA 484PF
UT WOS:000171698200009
PM 11739067
ER

PT J
AU Niida, Y
   Stemmer-Rachamimov, AO
   Logrip, M
   Tapon, D
   Perez, R
   Kwiatkowski, DJ
   Sims, K
   MacCollin, M
   Louis, DN
   Ramesh, V
AF Niida, Y
   Stemmer-Rachamimov, AO
   Logrip, M
   Tapon, D
   Perez, R
   Kwiatkowski, DJ
   Sims, K
   MacCollin, M
   Louis, DN
   Ramesh, V
TI Survey of somatic mutations in tuberous sclerosis complex (TSC)
   hamartomas suggests different genetic mechanisms for pathogenesis of TSC
   lesions
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID X-CHROMOSOME INACTIVATION; ALLELIC LOSS; EKER RAT; GERMLINE MUTATIONS;
   UNRELATED PATIENTS; GROWTH SUPPRESSOR; TUMOR SUPPRESSION; PRODUCT
   TUBERIN; HUMAN BRAIN; KIDNEY
AB Tuberous sclerosis complex (TSC), an autosomal dominant disease caused by mutations in either TSC1 or TSC2, is characterized by the development of hamartomas in a variety of organs. Concordant with the tumor-suppressor model, loss of heterozygosity (LOH) is known to occur in these hamartomas at loci of both TSC1 and TSC2. LOH has been documented in renal angiomyolipomas (AMLs), but loss of the wild-type allele in cortical tubers appears to be very uncommon. Analysis of second, somatic events in tumors for which the status of both TSC1 and TSC2 is known is essential for exploration of the pathogenesis of TSC-lesion development. We analyzed 24 hamartomas from 10 patients for second-hit mutations, by several methods, including LOH, scanning of all exons of both TSC1 and TSC2, promoter methylation of TSC2, and clonality analysis. Our results document loss of the wild-type allele in six of seven AMLs, without evidence of the inactivation of the second allele in many of the other lesions, including tumors that appear to be clonally derived. Laser-capture microdissection further demonstrated loss of the second allele in all three cellular components of an AML. This study thus provides evidence that, in both TSC1 and TSC2, somatic mutations resulting in the loss of wild-type alleles may not be necessary in some tumor types-and that other mechanisms may contribute to tumorigenesis in this setting.
C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
   Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA USA.
   Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA.
   Kanazawa Univ, Fac Med, Sch Med, Dept Pediat, Kanazawa, Ishikawa 920, Japan.
   Brigham & Womens Hosp, Div Hematol, Genet Lab, Boston, MA 02115 USA.
RP Ramesh, V (reprint author), Bldg 149,13th St, Charlestown, MA 02129 USA.
EM ramesh@helix.mgh.harvard.edu
FU NINDS NIH HHS [NS31535, NS24279, P01 NS024279, R01 NS031535, R37
   NS031535]
NR 50
TC 122
Z9 127
U1 0
U2 5
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 SEP
PY 2001
VL 69
IS 3
BP 493
EP 503
DI 10.1086/321972
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 459VD
UT WOS:000170271400003
PM 11468687
ER

PT J
AU Siegel, D
   Lopez, J
   Meier, J
   Cunningham, F
AF Siegel, D
   Lopez, J
   Meier, J
   Cunningham, F
TI Changes in the pharmacologic treatment of hypertension in the department
   of veterans affairs 1997-1999: Decreased use of calcium antagonists and
   increased use of beta-blockers and thiazide diuretics
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE adrenergic beta-antagonists; angiotensin converting enzyme inhibitors;
   calcium channel blockers; cost control; diuretics; health care costs;
   hypertension
ID ANTIHYPERTENSIVE DRUGS; MYOCARDIAL-INFARCTION; CHANNEL BLOCKERS;
   BLOOD-PRESSURE; UNITED-STATES; TRENDS; THERAPY; HEALTH; CARE; RISK
AB Older studies of antihypertensive treatment have shown that prescribing patterns are not consistent with recommendations from expert national panels. We determined whether prescribing patterns for antihypertensive drugs changed recently in the largest integrated health care system in the United States. Specifically, we determine 1) patterns of antihypertensive medication use at all Department of Veterans Affairs (VA) medical facilities for fiscal years 1997 to 1999, 2) the cost of this care, and 3) savings associated with changes in treatment patterns. Data were aggregated by individual medication as well as by antihypertensive drug class. Estimates of VA national antihypertensive drug costs are based on the median cost and the number of units for each dosage form of each medication dispensed at all facilities.
   At VA medical facilities, calcium antagonist use went from 33% to 29.3% of antihypertensive treatment days between 1997 and 1999, angiotensin converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB) use from 36.4% to 36.8%, beta -blockers from 19.1% to 21.1%, and thiazide diuretic use from at 11.5% to 12.8%. If treatment patterns had remained the same between 1997 and 1999 in terms of the proportion of medications from each drug class, an additional six million dollars would have been spent on antihypertensive medications in 1999.
   Although calcium antagonists and ACE inhibitors/ARB remained the most commonly dispensed antihypertensives at VA facilities from 1997 to 1999, there was a proportional decrease in calcium antagonist use and an increase in the use of thiazide diuretics and beta -blockers. These changes were consistent with improved compliance with VA national guidelines. The cost implications of these changes in practice patterns were considerable. Am J Hypertens 2001; 14:957-962 (C) 2001 American Journal of Hypertension, Ltd.
C1 No Calif Hlth Care Syst, Dept Vet Affairs, Med Serv, Mather, CA 95655 USA.
   Univ Calif Davis, Sch Med, Dept Med, Davis, CA 95616 USA.
   No Calif Hlth Care Syst, Serv Pharm, Dept Vet Affairs, Martinez, CA USA.
   Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA.
   Univ Pacific, Sch Pharm, Stockton, CA 95211 USA.
   US Dept Vet Affairs, Pharm Benefits Management Strateg Hlth Grp, Hines, IL 60141 USA.
RP Siegel, D (reprint author), No Calif Hlth Care Syst, Dept Vet Affairs, Med Serv, 111,10535 Hosp Way, Mather, CA 95655 USA.
NR 25
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 0895-7061
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD SEP
PY 2001
VL 14
IS 9
BP 957
EP 962
DI 10.1016/S0895-7061(01)02185-9
PN 1
PG 6
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 473KY
UT WOS:000171044100017
PM 11587164
ER

PT J
AU Whitsel, EA
   Boyko, EJ
   Matsumoto, AM
   Anawalt, BD
   Siscovick, DS
AF Whitsel, EA
   Boyko, EJ
   Matsumoto, AM
   Anawalt, BD
   Siscovick, DS
TI Intramuscular testosterone esters and plasma lipids in hypogonadal men:
   A meta-analysis
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEIN; HORMONE-BINDING GLOBULIN; CLINICAL
   RESEARCH-CENTER; ENDOGENOUS SEX-HORMONES; REPLACEMENT THERAPY;
   CHOLESTEROL LEVELS; CARDIOVASCULAR-DISEASE; SYSTEMATIC REVIEWS;
   PUBLICATION BIAS; BODY-COMPOSITION
AB PURPOSE: It is unclear whether intramuscular administration of testosterone esters to hypogonadal men is associated with changes in plasma lipids. We therefore analyzed 19 studies published between 1987 and 1999 that focused on male subjects with nonexperimental hypogonadism, treated subjects with an intramuscular testosterone ester and reported pretreatment and post-treatment concentrations of total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol, or total triglyceride.
   METHODS: We calculated study-specific, post-treatment minus pretreatment differences in each plasma lipid concentration (mean [95% confidence interval]). After testing of between-study homogeneity, we combined the study-specific differences. We then determined whether heterogeneity of differences could be explained in models of the differences on study and patient characteristics (mean +/- SE) before and after excluding extreme values using a multiple outlier procedure.
   RESULTS: The studies represented 272 hypogonadal men (age 44 +/- 4 years; 20% with hypergonadotropic hypogonadism; total testosterone 0.5 0.2 ng/mL) who received, on average, 179 +/- 13 mg intramuscular testosterone ester every 16 +/- 1 days for 6 +/- 1 months, Fixed-effects estimates of post-treatment minus pretreatment differences were -14 [ -17 to -11] mg/dL (total cholesterol), -1 [ - 8 to -1 ] mg/dL (LDL cholesterol), -4 [ - 5 to -2] mg/dL (HDL cholesterol), and -1 [-6 to + 4] mg/dL (triglyceride). Decreases in HDL cholesterol were larger at lower dosages of testosterone ester (r = -0.54, P = 0.055), but were not explained by attrition, regression to the mean, dosing frequency or duration, concomitant elevation of plasma total testosterone, aromatization of testosterone to estradiol, or other study and patient characteristics.
   CONCLUSION: Intramuscular administration of testosterone esters to hypogonadal men is associated with a small, dosage dependent decrease in HDL cholesterol and concomitant declines in total cholesterol and LDL cholesterol. The aggregate effect of these changes on cardiovascular risk remains unknown but deserves further study. (C) 2001 by Excerpta Medica, Inc.
C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Cardiovasc Dis Program, Chapel Hill, NC 27514 USA.
   Univ N Carolina, Sch Publ Hlth, Dept Med, Cardiovasc Dis Program, Chapel Hill, NC 27514 USA.
   Univ N Carolina, Sch Med, Dept Epidemiol, Cardiovasc Dis Program, Chapel Hill, NC 27514 USA.
   Univ N Carolina, Sch Med, Dept Med, Cardiovasc Dis Program, Chapel Hill, NC 27514 USA.
   Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA USA.
   Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA.
   Cardiovasc Hlth Res Unit, Seattle, WA USA.
   Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
   Univ Washington, Sch Med, Dept Epidemiol, Seattle, WA 98195 USA.
   Univ Washington, Sch Publ Hlth, Dept Med, Seattle, WA 98195 USA.
   Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
RP Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Cardiovasc Dis Program, Bank Amer Ctr,Suite 306,137 E Franklin St, Chapel Hill, NC 27514 USA.
FU NHLBI NIH HHS [5T32-HL-07055]
NR 65
TC 123
Z9 126
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD SEP
PY 2001
VL 111
IS 4
BP 261
EP 269
DI 10.1016/S0002-9343(01)00833-6
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA 476VE
UT WOS:000171248800002
PM 11566455
ER

PT J
AU DiSalvo, TG
   Normand, SLT
   Hauptman, PJ
   Guadagnoli, E
   Palmer, H
   McNeil, SJ
AF DiSalvo, TG
   Normand, SLT
   Hauptman, PJ
   Guadagnoli, E
   Palmer, H
   McNeil, SJ
TI Pitfalls in assessing the quality of care for patients with
   cardiovascular disease
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE; MEDICARE PATIENTS;
   HEART-FAILURE; MANAGED CARE; PRIVACY; INFORMATION; PROJECT;
   COMPLICATIONS; LEGISLATION
AB PURPOSE: There are no clinical performance measures for cardiovascular diseases that span the continuum of hospital through postdischarge ambulatory care. We tested the feasibility of developing and implementing such measures for patients with acute myocardial infarction, congestive heart failure, or hypertension.
   SUBJECTS AND METHODS: After reviewing practice guidelines and the medical literature, we developed potential measures related to therapy, diagnostic evaluation, and communication. We tested the feasibility of implementing the selected measures for 518 patients with myocardial infarction, 396 with heart failure, and 601 with hypertension who were enrolled in four major U.S. managed care plans at six geographic sites, using data from administrative claims, medical records, and patient surveys.
   RESULTS: Difficulties in obtaining timely data and small numbers of cases adversely affected measurement. We encountered 6- to 12-month delays, disagreement between principal discharge diagnosis as coded in administrative and records data (for 9% of myocardial infarction and 21 % of heart failure patients), missing medical records (20% for both myocardial infarction and heart failure patients), and problems in identifying physicians accountable for care. Low rates of performing key diagnostic tests (e.g., ejection fraction) excluded many cases from measures of appropriate therapy that were conditional on test results. Patient survey response rates were low.
   CONCLUSIONS: Constructing meaningful clinical performance measures is straightforward, but implementing them on a large scale will require improved data systems. Lack of standardized data captured at the point of clinical care and low rates of eligibility for key measures hamper measurement of quality of care. (C) 2001 by Excerpta Medica, Inc.
C1 Massachusetts Gen Hosp, Heart Failure Ctr, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA.
   Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA.
   Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Cambridge, MA 02138 USA.
   Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
   St Louis Univ Hosp, Cardiac Unit, St Louis, MO 63110 USA.
RP DiSalvo, TG (reprint author), Massachusetts Gen Hosp, Heart Failure Ctr, Bigelow 630,Fruit St, Boston, MA 02114 USA.
FU AHRQ HHS [HS 09487]
NR 30
TC 15
Z9 15
U1 0
U2 0
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 SEP
PY 2001
VL 111
IS 4
BP 297
EP 303
DI 10.1016/S0002-9343(01)00842-7
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA 476VE
UT WOS:000171248800008
PM 11583014
ER

PT J
AU Costenbader, KH
   Kievel, RI
   Anderson, RJ
AF Costenbader, KH
   Kievel, RI
   Anderson, RJ
TI Eosinophilic fasciitis presenting as pitting edema of the extremities
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
   Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
   Boston Univ, Sch Med, Rheumatol & Gastroenterol Associates, Brockton, MA USA.
RP Costenbader, KH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, 55 Fruit St, Boston, MA 02114 USA.
NR 8
TC 10
Z9 10
U1 0
U2 0
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 SEP
PY 2001
VL 111
IS 4
BP 318
EP 320
DI 10.1016/S0002-9343(01)00839-7
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA 476VE
UT WOS:000171248800011
PM 11566463
ER

PT J
AU Louis, DN
   Holland, EC
   Cairncross, JG
AF Louis, DN
   Holland, EC
   Cairncross, JG
TI Glioma classification - A molecular reappraisal
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID GLIOBLASTOMA-MULTIFORME; OLIGODENDROGLIAL TUMORS; SUCCESSFUL
   CHEMOTHERAPY; ASTROCYTIC TUMORS; GENETIC-ANALYSIS; IN-VIVO; 1P;
   SURVIVAL; CELLS; 19Q
C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA.
   Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10021 USA.
   Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA.
   Mem Sloan Kettering Canc Ctr, Dept Cell Biol, New York, NY 10021 USA.
   Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada.
   Univ Western Ontario, Dept Oncol, London, ON, Canada.
   London Reg Canc Ctr, London, ON N6A 4L6, Canada.
RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, 149 13th St, Charlestown, MA 02129 USA.
FU NCI NIH HHS [CA894314, R01 CA057683, CA57683]
NR 40
TC 192
Z9 205
U1 0
U2 6
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2001
VL 159
IS 3
BP 779
EP 786
DI 10.1016/S0002-9440(10)61750-6
PG 8
WC Pathology
SC Pathology
GA 470LA
UT WOS:000170872400001
PM 11549567
ER

PT J
AU Skobe, M
   Hamberg, LM
   Hawighorst, T
   Schirner, M
   Wolf, GL
   Alitalo, K
   Detmar, M
AF Skobe, M
   Hamberg, LM
   Hawighorst, T
   Schirner, M
   Wolf, GL
   Alitalo, K
   Detmar, M
TI Concurrent induction of lymphangiogenesis, angiogenesis, and macrophage
   recruitment by vascular endothelial growth factor-C in melanoma
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID LIGAND VEGF-C; BREAST-CANCER; LYMPHATIC ENDOTHELIUM; INITIAL LYMPHATICS;
   TYROSINE KINASES; TRANSGENIC MICE; KAPOSIS-SARCOMA; RECEPTORS KDR; FLUID
   VOLUME; HUMAN SKIN
AB Interactions of tumor cells with lymphatic vessels are of paramount importance for tumor progression, however, the underlying molecular mechanisms are poorly understood. Whereas enlarged lymphatic vessels are frequently observed at the periphery of malignant melanomas, it has remained unclear whether intratumoral lymphangiogenesis occurs within these tumors. Here, we demonstrate the presence of intratumoral lymphatics and enlargement of lymphatic vessels at the tumor periphery in vascular endothelial growth factor (VEGF)-C-overexpressing human melanomas transplanted onto nude mice. VEGF-C expression also resulted in enhanced tumor angiogenesis, indicating a coordinated regulation of lymphangiogenesis and angiogenesis in melanoma progression. The specific biological effects of VEGF-C were critically dependent on its proteolytic processing in vivo. Furthermore, VEGF-C induced chemotaxis of macrophages in vitro and in vivo, revealing a potential function of VEGF-C as an immunomodulator. Taken together, our results identify VEGF-C as multifunctional factor involved in regulating tumor lymphangiogenesis, angiogenesis, and immune response.
C1 Massachusetts Gen Hosp, Dept Dermatol, CBRC, Charlestown, MA 02129 USA.
   Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA.
   Harvard Univ, Sch Med, Charlestown, MA USA.
   Schering AG, D-1000 Berlin, Germany.
   Univ Helsinki, Haartman Inst, Helsinki, Finland.
RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA.
RI Alitalo, Kari/J-5013-2014
OI Alitalo, Kari/0000-0002-7331-0902
FU NCI NIH HHS [CA69184, CA86410, R01 CA069184, R01 CA086410]
NR 66
TC 282
Z9 308
U1 0
U2 8
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2001
VL 159
IS 3
BP 893
EP 903
DI 10.1016/S0002-9440(10)61765-8
PG 11
WC Pathology
SC Pathology
GA 470LA
UT WOS:000170872400016
PM 11549582
ER

PT J
AU Gisselsson, D
   Hibbard, MK
   Dal Cin, P
   Sciot, R
   Hsi, BL
   Kozakewich, HP
   Fletcher, JA
AF Gisselsson, D
   Hibbard, MK
   Dal Cin, P
   Sciot, R
   Hsi, BL
   Kozakewich, HP
   Fletcher, JA
TI PLAG1 alterations in lipoblastoma - Involvement in varied mesenchymal
   cell types and evidence for alternative oncogenic mechanisms
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID ADIPOSE-TISSUE TUMORS; FACTOR HMGI-C; MYXOID LIPOSARCOMA; RING
   CHROMOSOMES; BINDING PROTEIN; SOLID TUMORS; GENE; FUSION; CHOP;
   DIFFERENTIATION
AB Lipoblastomas are rare soft tissue tumors that occur primarily in young children. They typically contain variably differentiated adipocytes, primitive mesenchymal cells, myxoid matrix, and fibrous trabeculae. Abnormalities in chromosome 8, leading to rearrangements of the PLAG1 gene, were demonstrated recently in four lipoblastomas. In the present report, we determine the frequency of PLAG1 alterations in 16 lipoblastomas from children aged 13 years or younger, and we also evaluate the stages of lipoblastoma differentiation at which PLAG1 genomic alterations are found. Eleven lipoblastomas (69%), including those with either classic or lipoma-like histology, had rearrangements of the 8q12 PLAG1 region. Another three lipoblastomas had polysomy for chromosome 8 In the absence of PLAG1 rearrangement. Only two cases (13%) lacked a chromosome 8 abnormality. Notably, the lipoblastomas with chromosome 8 polysomy had up to five copies of chromosome 8 as an isolated cytogenetic finding in an otherwise diploid cell. We also demonstrate that PLAG1 alterations are found in a spectrum of mesenchymal cell types in lipoblastomas, including lipoblasts, mature adipocytes, primitive mesenchymal cells, and fibroblastlike cells. This finding is consistent with neoplastic origin in a primitive mesenchymal precursor and with variable differentiation to a mature adipocyte end-point. Hence, our studies provide biological validation for the clinical observation that lipoblastomas can evolve into mature, lipoma-like, lesions. They also suggest that PLAG1 dosage alterations caused by polysomy 8 might represent an alternative oncogenic mechanism in lipoblastoma.
C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
   Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   Univ Hosp, Dept Clin Genet, Lund, Sweden.
   Univ Hosp, Dept Pathol, Louvain, Belgium.
RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
NR 28
TC 66
Z9 69
U1 0
U2 0
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2001
VL 159
IS 3
BP 955
EP 962
DI 10.1016/S0002-9440(10)61771-3
PG 8
WC Pathology
SC Pathology
GA 470LA
UT WOS:000170872400022
PM 11549588
ER

PT J
AU Deng, A
   Irizarry, MC
   Nitsch, RM
   Growdon, JH
   Rebeck, GW
AF Deng, A
   Irizarry, MC
   Nitsch, RM
   Growdon, JH
   Rebeck, GW
TI Elevation of cystatin C in susceptible neurons in Alzheimer's disease
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID HEREDITARY CEREBRAL-HEMORRHAGE; ENDOSOMAL-LYSOSOMAL SYSTEM; AMYLOID
   PRECURSOR PROTEIN; GAMMA-TRACE; BETA DEPOSITION; TRANSGENIC MICE;
   UP-REGULATION; GENE; RAT; EXPRESSION
AB A common polymorphism in the cystatin C gene is associated with increased risk of developing Alzheimer's disease (AD). To explore possible neuropathological consequences of this genetic association, we examined expression of cystatin C in brains from 22 AD and 11 control patients by immunohistochemistry. In the temporal cortex of aft AD brains, there was strong cystatin C immunostaining of neurons and activated glia, whereas staining was absent or minimal in 7 of the 11 control brains. Neuronal staining of cystatin C in AD brains was primarily limited to pyramidal neurons in cortical layers III and V, which are the neurons most susceptible to cell death in AD. The increase in cystatin C staining in AD was independent of cystatin C genotype. Immunostaining of cystatin C within neurons showed a punctate distribution, which co-localized with the endosomal/lysosomal proteinase, cathepsin B. A primarily glial source for cystatin C was suggested by parallel studies using in situ hybridization of mouse brain. In human AD brain, there was little co-localization of cystatin C with parenchymal A beta deposits, although a small fraction of cerebral blood vessels and neurofibrillary tangles were cystatin C-positive. The regional distribution of cystatin C neuronal immunostaining also duplicated the pattern of neuronal susceptibility in AD brains: the strongest staining was found in the entorhinal cortex, in the hippocampus, and in the temporal cortex; fewer pyramidal neurons were stained in frontal, parietal, and occipital lobes. These neuropathological observations reinforce the association between cystatin C and AD, and support a model of cystatin C involvement in the process of neuronal death in AD.
C1 Massachusetts Gen Hosp, Dept Neurol, Memory Disorders Clin, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Neurol, Alzheimers Res Unit, Boston, MA 02114 USA.
   Univ Zurich, Div Psychiat Res, Zurich, Switzerland.
RP Rebeck, GW (reprint author), Alzheimer Res Unit, 114 16th St, Charlestown, MA 02129 USA.
FU NIA NIH HHS [P50 AG005134]
NR 32
TC 69
Z9 70
U1 1
U2 8
PU AMER SOC INVESTIGATIVE PATHOLOGY, INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD SEP
PY 2001
VL 159
IS 3
BP 1061
EP 1068
DI 10.1016/S0002-9440(10)61781-6
PG 8
WC Pathology
SC Pathology
GA 470LA
UT WOS:000170872400032
PM 11549598
ER

PT J
AU Pantukosit, S
   Petchkrua, W
   Stiens, SA
AF Pantukosit, S
   Petchkrua, W
   Stiens, SA
TI Intersection syndrome in Buriram Hospital - A 4-yr prospective study
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE intersection syndrome; cumulative trauma disorder; overuse syndromes;
   regional musculoskeletal disorders; repetitive motion disorders
ID CUMULATIVE TRAUMA DISORDERS; UPPER EXTREMITY; INJURIES; FOREARM; WORK;
   HAND
AB Objective: To determine the prevalence, demographic characteristics, symptoms, treatment, and outcome of patients who presented to Buriram Provincial hospital and were diagnosed with intersection syndrome.
   Design: This was a 4-yr prospective study that included all patients with new complaints of forearm and hand pain who presented to Buriram hospital as inpatients or outpatients.
   Results: The prevalence of intersection syndrome was found to be 0.37% of all patients (8080) with arm or hand pain. Of the 30 patients presenting with intersection syndrome, all had forearm pain, 22 (73.3%) had swelling, and 12 (40%) had crepitus noted in the intersected region. Fourteen (46.7%) patients reported pain provoked with twisting hand motions with radial deviations, 4 (13.3%) with pulling, and 12 (40%) with combinations of multiple hand movements (threshing, planting, hammering, hand washing, spraying and cementing). The majority of the patients were male (70%) farmers (60%). Twenty-nine patients received nonoperative treatment, including modified work activities to reduce stress on the wrist, nonsteroidal anti-inflammatory, and analgesic medications. One patient received only analgesic medication. One patient additionally required a resting hand splint. Every patient was seen for follow-up within the next 7 days. By 12-18 months posttreatment, there were only 14 patients (46.6%) remaining in follow-up, none with any symptom recurrence.
   Conclusion: Intersection syndrome is a relatively uncommon, overused syndrome that is associated with repeated radial deviation of the wrist and responds favorably to conservative treatment.
C1 Buriram Provincial Hosp, Dept Orthoped, Buriram, Thailand.
   Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
   Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
RP Petchkrua, W (reprint author), Bangkok Gen Hosp, Bangkok Rehabil Ctr, 1 Soi Soonvijai 7,New Petchburi Rd, Bangkok 10320, Thailand.
NR 26
TC 13
Z9 15
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD SEP
PY 2001
VL 80
IS 9
BP 656
EP 661
DI 10.1097/00002060-200109000-00005
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 464ZW
UT WOS:000170564100005
PM 11523968
ER

PT J
AU Boninger, ML
   Chan, L
   Harvey, R
   Pine, ZM
   Helkowski, W
   Garrison, CJ
   Tran, T
   Levin, H
   Levy, CE
AF Boninger, ML
   Chan, L
   Harvey, R
   Pine, ZM
   Helkowski, W
   Garrison, CJ
   Tran, T
   Levin, H
   Levy, CE
TI Resident research education in physical medicine and rehabilitation - A
   practical approach
SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION
LA English
DT Article
DE research; education; rehabilitation; residency training
ID CLINICAL RESEARCH; MANAGED CARE; JOURNAL CLUB; USERS GUIDES; PROGRAMS;
   PUBLICATIONS; ATTITUDES; DECISION; FACULTY; IMPACT
AB The Accreditation Council for Graduate Medical Education includes training in research as a required component of physical medicine and rehabilitation residency programs. Unfortunately, there is a lack of practical information on how to meet this requirement. In this paper, information is provided for individuals involved in resident education on how to teach residents about research.
C1 Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15213 USA.
   VA Pittsburgh Healthcare Syst, VA Ctr Excellence Wheelchairs & Related Technol, Human Engn Res Labs, Pittsburgh, PA USA.
   Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA.
   Rehabil Inst Chicago, Dept Phys Med & Rehabil, Chicago, IL 60611 USA.
   Univ Calif San Francisco, Mt Zion Med Ctr, Dept Med, Div Geriatr, San Francisco, CA 94120 USA.
   Ctr Excellence Acad Geriatr, San Francisco, CA USA.
   Baylor Univ, Med Ctr, Dept Phys Med & Rehabil, Dallas, TX USA.
   Baylor Coll Med, Dept Phys Med & Rehabil, Dallas, TX USA.
   N Florida S Georgia Vet Hlth Syst, Phys Med & Rehabil Serv, Gainesville, FL USA.
   Univ Florida, Dept Orthopaed & Rehabil, Gainesville, FL USA.
RP Boninger, ML (reprint author), Univ Pittsburgh, Dept Phys Med & Rehabil, 201 Kaufmann Bldg,3471 5th Ave, Pittsburgh, PA 15213 USA.
OI Boninger, Michael/0000-0001-6966-919X
NR 51
TC 8
Z9 8
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0894-9115
J9 AM J PHYS MED REHAB
JI Am. J. Phys. Med. Rehabil.
PD SEP
PY 2001
VL 80
IS 9
BP 706
EP 712
DI 10.1097/00002060-200109000-00013
PG 7
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 464ZW
UT WOS:000170564100011
PM 11523974
ER

PT J
AU Livingston, EH
   Lee, S
AF Livingston, EH
   Lee, S
TI Body surface area prediction in normal-weight and obese patients
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE body height; body weight; anthropometry; biological models
ID HEIGHT; CURVES
AB None of the equations frequently used to predict body surface area (BSA) has been validated for obese patients. We applied the principles of body size scaling to derive an improved equation predicting BSA solely from a patient's weight. Forty-five patients weighing from 51.3 to 248.6 kg had their height and weight measured on a calibrated scale and their BSA calculated by a geometric method. Data were combined with a large series of published BSA estimates. BSA prediction with the commonly used Du Bois equation underestimated BSA in obese patients by as much as 20%. The equation we derived to relate BSA to body weight was a power function: BSA (m(2)) = 0.1173 x Wt (kg)(0.6466). Below 10 kg, this equation deviated significantly from the BSA vs. body weight curve, necessitating a different set of coefficients: BSA (m(2)) = 0.1037 x Wt (kg)(0.6724). Covariance of height and weight for patients weighing <80 kg reduced the Du Bois BSA-predicting equation to a power function, explaining why it provides good BSA predictions for normal-size patients but fails with obesity.
C1 Vet Affairs Med Ctr, VA Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA 90073 USA.
   Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA 90073 USA.
RP Livingston, EH (reprint author), Vet Affairs Med Ctr, VA Greater Los Angeles Hlth Care Syst, Dept Surg, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
NR 13
TC 75
Z9 77
U1 1
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 SEP
PY 2001
VL 281
IS 3
BP E586
EP E591
PG 6
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 465BZ
UT WOS:000170569900020
PM 11500314
ER

PT J
AU Motomura, K
   Ohata, M
   Satre, M
   Tsukamoto, H
AF Motomura, K
   Ohata, M
   Satre, M
   Tsukamoto, H
TI Destabilization of TNF-alpha mRNA by retinoic acid in hepatic
   macrophages: implications for alcoholic liver disease
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE Kupffer cells; tumor necrosis factor-alpha mRNA stability; retinoic acid
   receptors; retinoid X receptors; retinoic acid response element
ID TUMOR-NECROSIS-FACTOR; VITAMIN-A; GENE-EXPRESSION; ALL-TRANS; KUPFFER
   CELLS; X-RECEPTOR; PERITONEAL-MACROPHAGES; RESPONSE ELEMENT;
   BINDING-PROTEINS; STELLATE CELLS
AB Retinoic acid (RA) inhibits hepatic macrophage (HM) cytokine expression, and retinoids are depleted in alcoholic liver disease (ALD). However, neither the causal link between the two nor the mechanism underlying RA-mediated HM inhibition is known. The aim of the present study was to determine the mechanism of RA-induced inhibition of HM tumor necrosis factor (TNF)-alpha expression and the relevance of this regulation to ALD. Treatment with all-trans RA (500 nM) caused a 50% inhibition in lipopolysaccharide (LPS)-stimulated TNF-alpha expression by cultured normal rat HM. The mRNA levels for inducible nitric oxide synthase, interleukin (IL)-6, IL-1 alpha, and IL-1 beta were also reduced, whereas those for transforming growth factor-beta1, MMP-9, and membrane cofactor protein-1 were unaffected. The inhibitory effect on TNF-alpha expression was reproduced by LG268, a retinoid X receptor (RXR)-specific ligand, but not by TTNPB, an RA receptor (RAR)-specific ligand. RA did not alter LPS-stimulated NF-kB and activation protein-1 binding but significantly decreased TNF-alpha mRNA stability in HM. HM isolated from the ALD model showed significant decreases in all-trans RA (-48%) and 9-cis RA (-61%) contents, RA response element (RARE) binding, and mRNA levels for RAR beta, RYR alpha, and cytosolic retinol binding protein-1, whereas TNF-alpha mRNA expression was induced. TNF-alpha mRNA stability was increased in these cells, and an ex vivo treatment with all-trans RA normalized both RAR beta and TNF-alpha mRNA levels. These results demonstrate the RA-induced destabilization of TNF-alpha mRNA by cultured HM and the association of RA depletion with increased TNF-alpha mRNA stability in HM from experimental ALD. These findings suggest that RA depletion primes HM for proinflammatory cytokine expression in ALD, at least in part, via posttranscriptional regulation.
C1 Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA.
   Univ So Calif, Sch Med, Dept Med, Los Angeles, CA 90033 USA.
   Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA.
   Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA 91343 USA.
RP Tsukamoto, H (reprint author), Univ So Calif, Keck Sch Med, Dept Pathol, MMR 402,1333 San Pablo St, Los Angeles, CA 90033 USA.
FU NIAAA NIH HHS [R37-AA-06603, P50-AA-11999]; NIDDK NIH HHS [P30-DK-48522]
NR 55
TC 28
Z9 30
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 SEP
PY 2001
VL 281
IS 3
BP E420
EP E429
PG 10
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 465BZ
UT WOS:000170569900002
PM 11500296
ER

PT J
AU Tawfeek, HAW
   Che, J
   Qian, F
   Abou-Samra, AB
AF Tawfeek, HAW
   Che, J
   Qian, F
   Abou-Samra, AB
TI Parathyroid hormone receptor internalization is independent of protein
   kinase A and phospholipase C activation
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE parathyroid hormone/parathyroid hormone-related peptide receptor; G
   protein-coupled receptor; cytoplasmic loops; extracelluar domains;
   internalization; green fluorescent protein
ID MESSENGER RIBONUCLEIC-ACIDS; OSTEOBLAST-LIKE CELLS; OPOSSUM
   KIDNEY-CELLS; SMOOTH-MUSCLE CELLS; PEPTIDE RECEPTOR; DOWN-REGULATION;
   PTH/PTHRP RECEPTOR; COUPLED RECEPTOR; PHORBOL ESTER; BETA(2)-ADRENERGIC
   RECEPTOR
AB Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) binding to their common receptor stimulates second messenger accumulation, receptor phosphorylation, and internalization. LLC-PK1 cells expressing a green fluorescent protein-tagged PTH/PTHrP receptor show time- and dose-dependent receptor internalization. The internalized receptors colocalize with clathrin-coated pits. Internalization is stimulated by PTH analogs that bind to and activate the PTH/PTHrP receptor. Cell lines expressing a mutant protein kinase A regulatory subunit that is resistant to cAMP and/or a mutant receptor (DSEL mutant) that does not activate phospholipase C internalize their receptors normally. In addition, internalization of the wild-type receptor and the DSEL mutant is stimulated by the PTH analog [Gly(1),Arg(19)]hPTH-(1-28), which does not stimulate phospholipase C. Forskolin, IBMX, and the active phorbol ester, phorbol-12-myristate-13-acetate, did not promote receptor internalization or increase PTH-induced internalization. These data indicate that ligand-induced internalization of the PTH/PTHrP receptor requires both ligand binding and receptor activation but does not involve stimulation of adenylate cyclase/protein kinase A or phospholipase C/protein kinase C.
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Abou-Samra, AB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA.
FU NIDDK NIH HHS [DK-11794-26, DK-10087-01]
NR 76
TC 17
Z9 17
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD SEP
PY 2001
VL 281
IS 3
BP E545
EP E557
PG 13
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA 465BZ
UT WOS:000170569900016
PM 11500310
ER

PT J
AU Van Remmen, H
   Williams, MD
   Guo, ZM
   Estlack, L
   Yang, H
   Carlson, EJ
   Epstein, CJ
   Huang, TT
   Richardson, A
AF Van Remmen, H
   Williams, MD
   Guo, ZM
   Estlack, L
   Yang, H
   Carlson, EJ
   Epstein, CJ
   Huang, TT
   Richardson, A
TI Knockout mice heterozygous for Sod2 show alterations in cardiac
   mitochondrial function and apoptosis
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE permeability transition; oxidative stress
ID MANGANESE SUPEROXIDE-DISMUTASE; PERMEABILITY TRANSITION PORE;
   ADENINE-NUCLEOTIDE TRANSLOCASE; TUMOR-NECROSIS-FACTOR; FOCAL
   CEREBRAL-ISCHEMIA; MNSOD GENE-EXPRESSION; CYCLOSPORINE-A; CYTOCHROME-C;
   CELL-DEATH; GLUTATHIONE-PEROXIDASE
AB Heart mitochondria from heterozygous (Sod2(-/+)) knockout mice have a 50% reduction in manganese superoxide dismutase (MnSOD) activity. The decrease in MnSOD activity was associated with increased mitochondrial oxidative damage as demonstrated by a decrease in the activities of iron sulfhydryl proteins sensitive to oxygen stress (aconitase and reduced nicotinamide adenine dinucleotide-oxidoreductase). Mitochondrial function was altered in the Sod2(-/+) mice, as shown by decreased respiration by complex I and an increase in the sensitivity of the permeability transition to induction by calcium and t-butylhydroperoxide. The increased induction of the permeability transition in heart mitochondria from Sod2(-/+) mice was associated with increased release of cytochrome c and an increase in DNA fragmentation. Cardiomyocytes isolated from neonatal Sod2(-/+) and Sod2(-/-) mice were more sensitive to cell death than cardiomyocytes from Sod2(+/+) mice after t-butylhydroperoxide treatment, and this increased sensitivity was prevented by inhibiting the permeability transition with cyclosporin A. These experiments demonstrate that MnSOD may play an important role in the induction of the mitochondrial pathway of apoptosis in the heart, and this appears to occur primarily through the permeability transition.
C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA.
   S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78284 USA.
   Univ Calif San Francisco, Sam & Ann Barshop Ctr Longev & Aging Studies, San Francisco, CA 94143 USA.
   Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
RP Van Remmen, H (reprint author), Audie Murphy VA Hosp, GRECC 182,7400 Merton Minter Blvd, San Antonio, TX 78229 USA.
FU NIA NIH HHS [AG-15908, AG-16998, P03-AG-13319]
NR 68
TC 132
Z9 135
U1 0
U2 2
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 SEP
PY 2001
VL 281
IS 3
BP H1422
EP H1432
PG 11
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
   Disease
SC Cardiovascular System & Cardiology; Physiology
GA 467LR
UT WOS:000170705100055
PM 11514315
ER

PT J
AU Wetzel, RK
   Sweadner, KJ
AF Wetzel, RK
   Sweadner, KJ
TI Immunocytochemical localization of Na-K-ATPase alpha- and gamma-subunits
   in rat kidney
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE immunofluorescence; confocal microscopy; nephron; colocalization; sodium
   pump
ID RENAL MAGNESIUM LOSS; NEPHRON SEGMENTS; COLLECTING DUCT; SODIUM-PUMP;
   INSITU HYBRIDIZATION; INTERCALATED CELLS; ANTIGEN RETRIEVAL;
   GENE-EXPRESSION; CULTURED-CELLS; NA,K-ATPASE
AB The gamma -subunit of the Na-K-ATPase is a single-span membrane protein that alters the kinetic properties of the enzyme. It is expressed in the kidney, but our initial observations indicated that it is not present in all nephron segments (Arystarkhova E, Wetzel RK, Asinovski NK, and Sweadner KJ. J Biol Chem 274: 33183-33185, 1999). Here we used triple-label confocal immunofluorescence microscopy in rat kidney with antibodies to Na-KATPase alpha1- and gamma -subunits and nephron segment-specific markers. Na-K-ATPase alpha1-subunit stain was low but unambiguous in proximal segments, moderate in macula densa, connecting tubules, and cortical collecting ducts, high in thick ascending limb and distal convoluted tubules, and nearly undetectable in glomeruli, descending and ascending thin limb, and medullary collecting ducts. The gamma -subunit colocalized at staining levels similar to al-subunit, in basolateral membranes in all segments except cortical thick ascending limb and cortical collecting ducts, which had alpha1-subunit but no detectable gamma -subunit stain. Selective gamma -subunit expression may contribute to the variations in Na-K-ATPase properties in different renal segments.
C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA.
RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, 149 13th St, Charlestown, MA 02129 USA.
EM sweadner@helix.mgh.harvard.edu
FU NHLBI NIH HHS [5R01-HL-36271]
NR 51
TC 70
Z9 72
U1 3
U2 3
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 SEP
PY 2001
VL 281
IS 3
BP F531
EP F545
PG 15
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 471BN
UT WOS:000170907100019
PM 11502602
ER

PT J
AU Goff, DC
   Coyle, JT
AF Goff, DC
   Coyle, JT
TI The emerging role of glutamate in the pathophysiology and treatment of
   schizophrenia
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Review
ID METHYL-D-ASPARTATE; PHENCYCLIDINE-INDUCED DEFICITS; EMISSION-TOMOGRAPHY
   PET; TREATMENT-RESISTANT SCHIZOPHRENIA; RECEPTOR SUBUNIT EXPRESSION;
   GLYCINE ADJUVANT THERAPY; PLACEBO-CONTROLLED TRIAL; LONG-TERM
   POTENTIATION; MESSENGER-RNA LEVELS; HIGH-DOSE GLYCINE
AB Objective: Research has implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of schizophrenia. This review evaluates evidence from preclinical and clinical studies that brain glutamatergic neurotransmission is altered in schizophrenia, may affect symptom expression, and is modulated by antipsychotic drugs.
   Method: A comprehensive review of scientific articles published over the last decade that address the role of glutamate in the pathophysiology of schizophrenia was carried out.
   Results: Glutamatergic neurons are the major excitatory pathways linking the cortex, limbic system, and thalamus, regions that have been implicated in schizophrenia. Postmortem studies have revealed alterations in pre- and postsynaptic markers for glutamatergic neurons in several brain regions in schizophrenia. The N-methyl-D-aspartic acid (NMDA) subtype of glutamate receptor may be particularly important as blockade of this receptor by the dissociative anesthetics reproduces in normal subjects the symptomatic manifestations of schizophrenia, including negative symptoms and cognitive impairments, and increases dopamine release in the mesolimbic system. Agents that indirectly enhance NMDA receptor function via the glycine modulatory site reduce negative symptoms and variably improve cognitive functioning in schizophrenic subjects receiving typical antipsychotics.
   Conclusions. Dysfunction of glutamatergic neurotransmission may play an important role in the pathophysiology of schizophrenia, especially of the negative symptoms and cognitive impairments associated with the disorder, and is a promising target for drug development.
C1 Harvard Univ, Sch Med, Consolidated Dept Psychiat, Belmont, MA 02478 USA.
   Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA.
RP Coyle, JT (reprint author), Harvard Univ, Sch Med, Consolidated Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA.
FU NIMH NIH HHS [MH-51290, MH-54245, MH-57708, MH-606450]
NR 148
TC 564
Z9 580
U1 4
U2 44
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 SEP
PY 2001
VL 158
IS 9
BP 1367
EP 1377
DI 10.1176/appi.ajp.158.9.1367
PG 11
WC Psychiatry
SC Psychiatry
GA 468QP
UT WOS:000170769900002
PM 11532718
ER

PT J
AU Dracheva, S
   Marras, SAE
   Elhakem, SL
   Kramer, FR
   Davis, KL
   Haroutunian, V
AF Dracheva, S
   Marras, SAE
   Elhakem, SL
   Kramer, FR
   Davis, KL
   Haroutunian, V
TI N-methyl-D-aspartic acid receptor expression in the dorsolateral
   prefrontal cortex of elderly patients with schizophrenia
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID IONOTROPIC GLUTAMATE RECEPTORS; POST-MORTEM BRAINS; NMDA RECEPTORS;
   POSTSYNAPTIC DENSITY; ALZHEIMER-DISEASE; MOLECULAR BEACONS;
   CEREBRAL-CORTEX; BINDING-SITES; MULTIPLEX DETECTION; HUMAN HIPPOCAMPUS
AB Objective: The N-methyl-D-aspartic acid (NMDA) class of glutamate receptors has received attention in the pathophysiology of schizophrenia because of the similarity between some schizophrenic symptoms and symptoms caused by NMDA antagonists. To determine if NMDA receptor abnormalities were present at the mRNA level, expression of NMDA receptor (NR) subunits NR1, NR2A, and NR2B Was measured in specimens from the dorsolateral prefrontal cortex and the occipital cortex of elderly patients with schizophrenia and normal elderly subjects.
   Method: Postmortem specimens from antemortem assessed and diagnosed elderly patients with schizophrenia (N=26) were compared with those from a neuropathologically and neuropsychiatrically normal elderly comparison group (N=13) and from patients with Alzheimer's disease (N=10). The mRNA expression of the NR1, NR2A, and NR2B subunits and of postsynaptic density 95 (PSD-95), a protein associated with postsynaptic NMDA receptors, was studied with quantitative real-time reverse transcriptase polymerase chain reaction.
   Results: Expression of NR1 and NR2A but not NR2B subunits was higher in the dorsolateral prefrontal cortex and the occipital cortex of patients with schizophrenia than in the normal and Alzheimer's disease groups. In contrast, NR1 expression was significantly lower in the Alzheimer's disease group. Occipital cortex expression of PSD-95 was higher in the schizophrenic subjects and correlated strongly with the expression of NR2A and NR2B in both cortical regions and with expression of NR1 in the occipital cortex, These results were not influenced by neuroleptic exposure history, postmortem interval, or age of the subject,
   Conclusions: NMDA receptor subunits are abnormally expressed in elderly patients with schizophrenia, The disproportionate expression of the NR1 and NR2A subunits relative to NR2B expression may have implications for the pathophysiology of schizophrenia and the sensitivity of schizophrenic patients to glutamate and glutamatergic drugs.
C1 Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA.
   Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
   Publ Hlth Res Inst, Dept Mol Genet, New York, NY USA.
RP Haroutunian, V (reprint author), Bronx Vet Adm Med Ctr, 130 W Kings Bridge Rd, Bronx, NY 10468 USA.
FU NHLBI NIH HHS [HL-43521]; NIMH NIH HHS [MH-45212]
NR 96
TC 134
Z9 137
U1 0
U2 8
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 SEP
PY 2001
VL 158
IS 9
BP 1400
EP 1410
DI 10.1176/appi.ajp.158.9.1400
PG 11
WC Psychiatry
SC Psychiatry
GA 468QP
UT WOS:000170769900008
PM 11532724
ER

PT J
AU Franko, DL
   Blais, MA
   Becker, AE
   Delinsky, SS
   Greenwood, DN
   Flores, AT
   Ekeblad, ER
   Eddy, KT
   Herzog, DB
AF Franko, DL
   Blais, MA
   Becker, AE
   Delinsky, SS
   Greenwood, DN
   Flores, AT
   Ekeblad, ER
   Eddy, KT
   Herzog, DB
TI Pregnancy complications and neonatal outcomes in women with eating
   disorders
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID ANOREXIA-NERVOSA; BULIMIA-NERVOSA; IMPACT; REPRODUCTION; DEPRESSION;
   BEHAVIOR
AB Objective: This study reported pregnancy complications and neonatal outcomes for 49 live births in a group of women with eating disorders who were prospectively followed.
   Method: Subjects were recruited from 246 women participating in a longitudinal study of anorexia nervosa and bulimia nervosa, now in its 12th year. Subjects were interviewed by trained assistants and completed a brief self-report instrument that assessed both birth statistics and birth-related complications. Medical records and/or self-report data describing the neonates' birth status were obtained.
   Results: The majority of the women with eating disorders had normal pregnancies, resulting in healthy babies. Across the group, the mean length of pregnancy was 38.7 weeks, the mean birth weight was 7.6 lb, and mean Apgar scores at 1 and 5 minutes after birth were 8.2 and 9.0, respectively. Most outcomes were positive; however, three babies (6.1%) had birth defects, and 17 (34.7%) of the women experienced postpartum depression. The mean number of obstetric complications in the group was 1.3, and 13 (26.5%) of the women delivered by cesarean section. Women who showed symptoms of either anorexia nervosa or bulimia nervosa during pregnancy had a higher frequency of birth by cesarean section and postpartum depression than did nonsymptomatic women.
   Conclusions: Pregnant women with active eating disorders appear to be at greater risk for delivery by cesarean section and for postpartum depression. Pregnant women with past or current eating disorders should be viewed as being at high risk and monitored closely both during and after pregnancy to optimize maternal and fetal outcomes.
C1 Harvard Univ, Massachusetts Gen Hosp, Eating Disorders Unit, Sch Med,Dept Psychiat, Boston, MA 02114 USA.
RP Herzog, DB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Eating Disorders Unit, Sch Med,Dept Psychiat, 15 Parkman St,725ACC, Boston, MA 02114 USA.
FU NIMH NIH HHS [MH-38333]
NR 21
TC 88
Z9 90
U1 0
U2 10
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 SEP
PY 2001
VL 158
IS 9
BP 1461
EP 1466
DI 10.1176/appi.ajp.158.9.1461
PG 6
WC Psychiatry
SC Psychiatry
GA 468QP
UT WOS:000170769900016
PM 11532732
ER

PT J
AU Barbeau, EM
   Li, Y
   Sorensen, G
   Conlan, KM
   Youngstrom, R
   Emmons, K
AF Barbeau, EM
   Li, Y
   Sorensen, G
   Conlan, KM
   Youngstrom, R
   Emmons, K
TI Coverage of smoking cessation treatment by union health and welfare
   funds
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID COST-EFFECTIVENESS; CIGARETTE-SMOKING
AB Objectives. This study determined the level of insurance coverage for smoking cessation treatment and factors associated with coverage among health and welfare funds affiliated with a large labor union.
   Methods. A self-administered written survey was mailed to fund and union officials. Analyses were conducted by chi (2) tests.
   Results. Twenty-nine percent of funds provided coverage for some type of smoking cessation treatment,with the odds of coverage significantly increased among funds whose administrators reported having received members' requests for smoking cessation treatment in the past year (odds ratio = 4.9, P = .05).
   Conclusions. Coverage for smoking cessation services is low, comparable to coverage offered by other health insurers. Interventions with union members and fund officials are needed to provide union members with access to affordable and effective smoking cessation treatments.
C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
   Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA.
   Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA.
   Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   Laborers Hlth & Safety Fund N Amer, Washington, DC USA.
RP Barbeau, EM (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA.
NR 19
TC 17
Z9 17
U1 2
U2 2
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 SEP
PY 2001
VL 91
IS 9
BP 1412
EP 1415
DI 10.2105/AJPH.91.9.1412
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 466MY
UT WOS:000170650400027
PM 11527772
ER

PT J
AU Schackman, BR
   Goldie, SJ
   Weinstein, MC
   Losina, E
   Zhang, H
   Freedberg, KA
AF Schackman, BR
   Goldie, SJ
   Weinstein, MC
   Losina, E
   Zhang, H
   Freedberg, KA
TI Cost-effectiveness of earlier initiation of antiretroviral therapy for
   uninsured HIV-infected adults
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID UNITED-STATES; PLUS INDINAVIR; CARE; AIDS; PLASMA; VIRUS; ZIDOVUDINE;
   LAMIVUDINE; DISEASE; PEOPLE
AB Objectives. This study was designed to examine the societal cost-effectiveness and the impact on government payers of earlier initiation of antiretroviral therapy for uninsured HIV-infected adults.
   Methods. A state-transition simulation model of HIV disease was used. Data were derived from the Multicenter AIDS Cohort Study, published randomized trials, and medical care cost estimates for all government payers and for Massachusetts, New York, and Florida.
   Results, Quality-adjusted life expectancy increased from 7.64 years with therapy initiated at 200 CD4 cells/muL to 8.21 years with therapy initiated at 500 CD4 cells/muL. Initiating therapy at 500 CD4/muL was a more efficient use of resources than initiating therapy at 200 CD4/muL and had an incremental cost-effectiveness ratio of $17 300 per quality-adjusted life-year gained, compared with no therapy. Costs to state payers in the first 5 years ranged from $5 500 to $24 900 because of differences among the states in the availability of federal funds for AIDS drug assistance programs.
   Conclusions. Antiretroviral therapy initiated at 500 CD4 cells/mul. is cost-effective from a societal perspective compared with therapy initiated later. States should consider Medicaid waivers to expand access to early therapy.
C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Risk Anal, Boston, MA 02115 USA.
   Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA.
   Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
RP Schackman, BR (reprint author), Cornell Univ, Weill Med Coll, Dept Publ Hlth, 411 E 69th St, New York, NY 10021 USA.
FU NIAID NIH HHS [R01 AI042006, R01AI42006]; NLM NIH HHS [LM0709207, T15
   LM007092]; PHS HHS [U64/CCU 1114927]
NR 41
TC 39
Z9 39
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 SEP
PY 2001
VL 91
IS 9
BP 1456
EP 1463
DI 10.2105/AJPH.91.9.1456
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 466MY
UT WOS:000170650400037
PM 11527782
ER

PT J
AU Barr, RG
   Diez-Roux, AV
   Knirsch, CA
   Pablos-Mendez, A
AF Barr, RG
   Diez-Roux, AV
   Knirsch, CA
   Pablos-Mendez, A
TI Neighborhood poverty and the resurgence of tuberculosis in New York
   City, 1984-1992
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; FOREIGN-BORN PERSONS; UNITED-STATES;
   RESISTANT TUBERCULOSIS; RISK-FACTOR; TRANSMISSION; EPIDEMIOLOGY;
   DEPRIVATION; ENGLAND; NOTIFICATIONS
AB Objectives. The resurgence of tuberculosis (TB) in New York City has been attributed to AIDS and immigration; however the role of poverty in the epidemic is unclear. We assessed the relation between neighborhood poverty and TB at the height of the epidemic and longitudinally from 1984 through 1992.
   Methods. Census block groups were used as proxies for neighborhoods. For each neighborhood, we calculated TB and AIDS incidence in 1984 and 1992 with data from the Bureaus of Tuberculosis Control and AIDS Surveillance and obtained poverty rates from the census.
   Results. For 1992, 3343 TB cases were mapped to 5482 neighborhoods, yielding a mean incidence of 46.5 per 100000. Neighborhood poverty was associated with TB (relative risk = 1.33; 95% confidence interval = 1.30, 1.36 per 10% increase in poverty). This association persisted after adjustment for AIDS, proportion foreign-born, and race/ethnicity. Neighborhoods with declining income from 1980 to 1990 had larger increases in TB incidence than did neighborhoods with increasing income.
   Conclusions. Leading up to and at the height of the TB epidemic in New York City, neighborhood poverty was strongly associated with TB incidence. Public health interventions should target impoverished areas.
C1 Columbia Univ Coll Phys & Surg, Columbia Presbyterian Med Ctr, Div Gen Med, New York, NY 10032 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA.
   Columbia Univ, Sch Publ Hlth, Div Epidemiol, New York, NY USA.
   Columbia Univ Coll Phys & Surg, Div Infect Dis, New York, NY 10032 USA.
   Rockefeller Fdn, New York, NY USA.
RP Barr, RG (reprint author), Columbia Univ Coll Phys & Surg, Columbia Presbyterian Med Ctr, Div Gen Med, PH-9 East,622 W 168th St, New York, NY 10032 USA.
EM rgb9@columbia.edu
FU BHP HRSA HHS [PE-11001]
NR 43
TC 74
Z9 76
U1 0
U2 3
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD SEP
PY 2001
VL 91
IS 9
BP 1487
EP 1493
DI 10.2105/AJPH.91.9.1487
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 466MY
UT WOS:000170650400041
PM 11527786
ER

PT J
AU O'Neill, MJ
   Weissleder, R
   Gervais, DA
   Hahn, PF
   Mueller, PR
AF O'Neill, MJ
   Weissleder, R
   Gervais, DA
   Hahn, PF
   Mueller, PR
TI Tunneled peritoneal catheter placement under sonographic and
   fluoroscopic guidance in the palliative treatment of malignant ascites
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
ID DIALYSIS CATHETERS; COMPLICATIONS; EXPERIENCE; SHUNT
AB OBJECTIVE. We present a treatment for recurrent, symptomatic ascites in patients with malignant disease. This report summarizes our experience with percutaneous tunneled peritoneal catheters in 24 patients.
   SUBJECTS AND METHODS. Of the 40 consecutive patients who presented with at least four therapeutic paracenteses in a 4-week period, 24 patients underwent the percutaneous tunneled procedure. All had malignant ascites.
   RESULTS. All 24 patients had successful insertion of a permanent tunneled peritoneal drainage catheter. Eighteen were outpatients and six were inpatients. All patients were relieved of their clinical symptoms, including abdominal distention and dyspnea, and were relieved of lower extremity discomfort. The mean life span after catheter placement was 7.2 weeks. Twenty (83%) of the 24 patients were treated at home with their catheters in place. Three patients experienced minor complications from bacterial peritonitis, which responded to antibiotics. One patient had to have his catheter removed.
   CONCLUSION. Percutaneous placement of specialized tunneled catheters appears to be a viable and safe technique in patients who have symptomatic ascites that require frequent therapeutic paracentesis for relief of symptoms.
C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP O'Neill, MJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA.
NR 13
TC 24
Z9 26
U1 0
U2 2
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 SEP
PY 2001
VL 177
IS 3
BP 615
EP 618
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 466XT
UT WOS:000170672000018
PM 11517056
ER

PT J
AU Hinkin, CH
   Castellon, SA
   Dickson-Fuhrman, E
   Daum, G
   Jaffe, J
   Jarvik, L
AF Hinkin, CH
   Castellon, SA
   Dickson-Fuhrman, E
   Daum, G
   Jaffe, J
   Jarvik, L
TI Screening for drug and alcohol abuse among older adults using a modified
   version of the CAGE
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Article
ID SUBSTANCE-ABUSE; QUESTIONNAIRE; DISORDERS; DRINKING
AB This study examined the sensitivity, specificity, and receiver operating characteristics (ROC) curves of a modified version of the CAGE, a screening measure used in the detection of older alcohol- and drug-abusing individuals. In a retrospective review of clinical records of 976 patients screened by a geriatric substance abuse program, the authors examined patients' responses on a modified version of the CAGE that included queries regarding drug use. The CAGE was administered to individuals age 50 or over drawn from three diagnostic groups: alcohol abuse/dependence, drug abuse/dependence, and normal controls. Analysis of variance and discriminant function analyses revealed that the modified CAGE was able to discriminate both alcohol and drug abusers from controls. Analyses examining test sensitivity, specificity, and ROC curves revealed the CAGE to demonstrate excellent sensitivity but poor specificity. Omitting the "cut down" item from the CAGE significantly improved specificity with only a modest drop in sensitivity. Given the ease of administration and sensitivity to both alcohol and drug abuse, these data suggest that the modified CAGE is well suited as a screening instrument for geriatric drug and alcohol abuse.
C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
   VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
   Univ Maryland, Dept Psychiat, Baltimore, MD USA.
RP Hinkin, CH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA.
NR 22
TC 28
Z9 28
U1 0
U2 2
PU BRUNNER-ROUTLEDGE
PI PHILADELPHIA
PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA
SN 1055-0496
J9 AM J ADDICTION
JI Am. J. Addict.
PD FAL
PY 2001
VL 10
IS 4
BP 319
EP 326
PG 8
WC Substance Abuse
SC Substance Abuse
GA 507UP
UT WOS:000173049900007
PM 11783746
ER

PT J
AU Hohn, DJ
   Deschler, DG
   Tucker, JA
AF Hohn, DJ
   Deschler, DG
   Tucker, JA
TI Central incisor width as a predictor of appropriate curette size in
   adenoidectomy
SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY
LA English
DT Article
DE adenoidectomy; central incisor width; eustachian tube dysfunction;
   inter-tubarius width
ID TONSILLECTOMY
AB As inadvertent eustachian tube injury during adenoidectomy can have serious short- and long-term implications, a simple anatomic correlate that could predict the optimal curette choice for adenoidectomy, especially in severely hypertrophic cases, is beneficial. This study evaluates the correlation of the distance between the lateral borders of the upper central incisors and the distance between the tori tubarius in the nasopharynx. One hundred one consecutive patients undergoing adenoidectomy at a pediatric tertiary care hospital were enrolled in this study. The patients ranged in age from 7 months to 15 years. No complications were noted in any of the procedures. During the operation, the distance between the central upper incisors was measured in millimeters, as was the inter-tubarius width (ITW). A multiple regression analysis was completed to assess the correlation between central incisor width and ITW Age and inter-incisor width were positively correlated with ITW in a statistically significant manner (p =.007 and p =.006, respectively). The distance between the lateral borders of the upper central incisors predicts the distance between the tori tubarius in the nasopharynx. Therefore, an adenoid curette the window of which does not overlap the lateral aspects of the central upper incisors can be used relatively safely, even in fields with poor visualization.
C1 St Christophers Hosp Children, Dept Pediat Otolaryngol Head & Neck Surg, Philadelphia, PA 19134 USA.
   Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
RP Hohn, DJ (reprint author), St Christophers Hosp Children, Dept Pediat Otolaryngol Head & Neck Surg, Erie Ave & Front St, Philadelphia, PA 19134 USA.
NR 9
TC 0
Z9 2
U1 1
U2 1
PU ANNALS PUBL CO
PI ST LOUIS
PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA
SN 0003-4894
J9 ANN OTO RHINOL LARYN
JI Ann. Otol. Rhinol. Laryngol.
PD SEP
PY 2001
VL 110
IS 9
BP 841
EP 843
PG 3
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 474GD
UT WOS:000171097200007
PM 11558760
ER

PT J
AU Merchant, SN
   McKenna, MJ
   Baldwin, CT
   Milunsky, A
   Nadol, JB
AF Merchant, SN
   McKenna, MJ
   Baldwin, CT
   Milunsky, A
   Nadol, JB
TI Otopathology in a case of type I Waardenburg's syndrome
SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY
LA English
DT Article
DE gene mutation; histopathology; temporal bone; Waardenburg's syndrome
ID HUP2 PAIRED DOMAIN; INNER-EAR; HUMAN HOMOLOG; HEARING-LOSS; PAX-3;
   MELANOCYTES; MUTATIONS; GENE
AB We report a case of type I Waardenburg's syndrome that provides insight into the etiopathogenesis of sensorineural hearing loss (SNHL) in this syndrome. The subject, a 76-year-old woman with type I Waardenburg's syndrome (dystopia canthorum, heterochromia irides, and white hair), had congenital low-frequency SNHL in her right ear only, which had remained relatively stable throughout her life. Blood leukocyte DNA studies revealed a PAX-3 mutation with a I base pair C-to-A substitution in exon 5 at base 602. Light microscopic studies of the right cochlea showed intact neurosensory structures in only the lower basal turn, with the remainder of the cochlea showing absence of melanocytes, absence of stria vascularis, missing hair cells, dysmorphogenesis. of the rectorial membrane, and lack of peripheral processes of the spiral ganglion cells. There was pathological alteration of the vestibular dark cells with marked reduction of melanocytes associated with these dark cells. The left inner ear was normal, with a full complement of neurosensory structures, including melanocytes. Because the PAX-3 gene is involved in neural crest development and melanocytes migrate from the neural crest to the ear, the findings in this case are consistent with the hypothesis that defective melanocyte migration or defective melanocyte function results in defective development of the stria vascularis (and perhaps other structures of the ear), leading to SNHL.
C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
   Massachusetts Eye & Ear Infirm, Otopathol Lab, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
   Boston Univ, Sch Med, Ctr Human Genet, Boston, MA 02118 USA.
RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
FU NIDCD NIH HHS [5 R01 DC03401]
NR 27
TC 12
Z9 12
U1 0
U2 2
PU ANNALS PUBL CO
PI ST LOUIS
PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA
SN 0003-4894
J9 ANN OTO RHINOL LARYN
JI Ann. Otol. Rhinol. Laryngol.
PD SEP
PY 2001
VL 110
IS 9
BP 875
EP 882
PG 8
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 474GD
UT WOS:000171097200013
PM 11558766
ER

PT J
AU Nadol, JB
   Shiao, JY
   Burgess, BJ
   Ketten, DR
   Eddington, DK
   Gantz, BJ
   Kos, I
   Montandon, P
   Coker, NJ
   Roland, JT
   Shallop, JK
AF Nadol, JB
   Shiao, JY
   Burgess, BJ
   Ketten, DR
   Eddington, DK
   Gantz, BJ
   Kos, I
   Montandon, P
   Coker, NJ
   Roland, JT
   Shallop, JK
TI Histopathology of cochlear implants in humans
SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY
LA English
DT Article
DE cochlear implantation; electrode trauma; neo-osteogenesis; spiral
   ganglion
ID DEAFENED GUINEA-PIG; HUMAN TEMPORAL BONES; ELECTRICAL-STIMULATION;
   SPIRAL GANGLION; INSERTION TRAUMA; ELECTRODE INSERTION; PATIENT;
   SURVIVAL; NERVE; ARRAY
AB The insertion of an intrascalar electrode array during cochlear implantation causes immediate damage to the inner ear and may result in delayed onset of additional damage that may interfere with neuronal stimulation. To date, there have been reports on fewer than 50 temporal bone specimens from patients who had undergone implantation during life. The majority of these were single-channel implants, whereas the majority of implants inserted today are multichannel systems. This report presents the histopathologic findings in temporal bones from 8 individuals who in life had undergone multichannel cochlear implantation, with particular attention to the type and location of trauma and to long-term changes within the cochlea. The effect of these changes on spiral ganglion cell counts and the correlation between speech comprehension and spiral ganglion cell counts were calculated. In 4 of the 8 cases, the opposite, unimplanted ear was available for comparison. In 3 of the 4 cases, there was no significant difference between the spiral ganglion cell counts on the implanted and unimplanted sides. In addition, in this series of 8 cases, there was an apparent negative correlation between residual spiral ganglion cell count and hearing performance during life as measured by single-syllable word recognition. This finding suggests that abnormalities in the central auditory pathways are at least as important as spiral ganglion cell loss in limiting the performance of implant users.
C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
   Univ Iowa Hosp & Clin, Dept Otolaryngol, Iowa City, IA 52242 USA.
   Baylor Coll Med, Dept Otolaryngol & Commun Sci, Houston, TX 77030 USA.
   NYU, Med Ctr, Dept Otolaryngol, New York, NY 10016 USA.
   Mayo Clin, Dept Otolaryngol, Rochester, MN USA.
   Univ Hosp Geneva, Dept Otolaryngol, Geneva, Switzerland.
   Taichung Vet Gen Hosp, Dept Otolaryngol, Taichung, Taiwan.
RP Nadol, JB (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
FU NIDCD NIH HHS [P50 DC000242]
NR 33
TC 150
Z9 152
U1 1
U2 4
PU ANNALS PUBL CO
PI ST LOUIS
PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA
SN 0003-4894
J9 ANN OTO RHINOL LARYN
JI Ann. Otol. Rhinol. Laryngol.
PD SEP
PY 2001
VL 110
IS 9
BP 883
EP 891
PG 9
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 474GD
UT WOS:000171097200014
PM 11558767
ER

PT J
AU Netscher, DT
   Eladoumikdachi, F
   Goodman, CM
AF Netscher, DT
   Eladoumikdachi, F
   Goodman, CM
TI Rectus abdominis muscle flaps used successfully for median sternotomy
   wounds after ipsilateral internal mammary artery ligation
SO ANNALS OF PLASTIC SURGERY
LA English
DT Article
ID RECONSTRUCTION; MEDIASTINITIS; INFECTIONS
AB Use of the rectus abdominis muscle for reconstruction based on its superior blood supply has been said by some to be contraindicated if the ipsilateral internal mammary artery (IMA) has been divided for reasons such as coronary artery bypass grafting. The authors describe 5 patients in whom either both IMAs were used for coronary revascularization or in whom there was a contralateral subcostal incision, and they were thus compelled to perform sternal reconstruction using at least one rectus abdominis muscle ipsilateral to prior IMA ligation. In all patients the muscle flap was used to reconstruct an open median sternotomy wound successfully. An injection study as well as a fresh cadaveric dissection revealed rich collateral circulation to the superior epigastric vascular pedicle through the musculophrenic artery as well as through the lower intercostal arteries. This case report and the series of 5 patients indicate that if elevation of the rectus muscle and division of the lateral segmental vessels is done only up to the costal margin, one can reliably maintain a viable rectus muscle flap, even in the face of prior ipsilateral IMA ligation. This enables useful reconstruction to the lower half of a sternal wound using the rectus abdominis muscle, requiring a pectoralis major muscle flap for the superior part of the wound.
C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA.
   Dept Vet Affairs Med Ctr, Houston, TX USA.
RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA.
NR 18
TC 13
Z9 17
U1 0
U2 0
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 SEP
PY 2001
VL 47
IS 3
BP 223
EP 228
DI 10.1097/00000637-200109000-00001
PG 6
WC Surgery
SC Surgery
GA 472EM
UT WOS:000170970600001
PM 11562023
ER

PT J
AU Balcom, JH
   Keck, T
   Warshaw, AL
   Antoniu, B
   Graeme-Cook, F
   Fernandez-del Castillo, C
AF Balcom, JH
   Keck, T
   Warshaw, AL
   Antoniu, B
   Graeme-Cook, F
   Fernandez-del Castillo, C
TI Telomerase activity in periampullary tumors correlates with aggressive
   malignancy
SO ANNALS OF SURGERY
LA English
DT Article; Proceedings Paper
CT 121st Annual Meeting of the American-Surgical-Association
CY APR 26-28, 2001
CL COLORADO SPRINGS, COLORADO
SP Amer Surg Assoc
ID RAS ONCOGENE ACTIVATION; PANCREATIC-CARCINOMA; HUMAN FIBROBLASTS; POINT
   MUTATIONS; BREAST-CANCER; LUNG CANCERS; ADENOCARCINOMA; CELLS;
   ASSOCIATION; DIAGNOSIS
AB Objective To determine the presence of telomerase activity in a variety of periampullary malignancies and pancreatic diseases and quantify its activity to establish any association with the stage or aggressiveness of malignancy.
   Summary Background Data Progressive shortening of telomeres, repetitive DNA sequences at the ends of chromosomes, plays a role in cell senescence. Telomerase catalyzes conservation of telomeric repeats and may promote cell immortality and hence malignancy. It is absent in normal tissues but upregulated in more than 80% of cancers.
   Methods Fresh specimens of 62 periampullary tumors were snap-frozen in liquid nitrogen and adjacent tissue was formalin-fixed for histopathology. The telomerase repeat amplification protocol (TRAP) was used to obtain telomerase DNA products. These were separated with gel electrophoresis, stained with SYBR green, and quantified by densitometry. Findings were confirmed with a fluorometric TRAP assay in which fluorescent primers specific for telomerase were selectively amplified in its presence.
   Results Telomerase activity was upregulated in 26 of 33 periampullary malignancies (79%): 17 of 21 pancreatic adenocarcinomas (81%), 2 of 2 cholangiocarcinomas, 2 of 2 duodenal carcinomas, and 5 of 8 ampullary carcinomas (63%). Poorly differentiated periampullary tumors had significantly higher telomerase activity than well-differentiated tumors, and tumors larger than 2 cm had significantly higher telomerase activity than those 2 cm or smaller. Pancreatic ductal adenocarcinomas with lymph node metastases had significantly greater activity than node-negative cancers. Two of 11 intraductal papillary mucinous tumors were positive for telomerase activity, but only in foci of invasive carcinoma. Chronic pancreatitis (n = 7), serous cystadenomas (n = 5), benign mucinous cystic neoplasms (n = 4), neuroendocrine cancer (n = 1), and acinar cell carcinoma (n = 1) had no detectable telomerase activity.
   Conclusion Telomerase activity is common in periampullary carcinomas. The magnitude of activity correlates with aggressiveness in pancreatic adenocarcinoma and may prove useful as a molecular index for biologic staging.
C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, WACC 336,55 Fruit St, Boston, MA 02114 USA.
NR 49
TC 18
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 SEP
PY 2001
VL 234
IS 3
BP 344
EP 350
DI 10.1097/00000658-200109000-00008
PG 7
WC Surgery
SC Surgery
GA 470LH
UT WOS:000170873100014
PM 11524587
ER

PT J
AU Khuri, SF
   Najjar, SF
   Daley, J
   Krasnicka, B
   Hossain, M
   Henderson, WG
   Aust, JB
   Bass, B
   Bishop, MJ
   Demakis, J
   DePalma, R
   Fabri, PJ
   Fink, A
   Gibbs, J
   Grover, F
   Hammermeister, K
   McDonald, G
   Neumayer, L
   Roswell, RH
   Spencer, J
   Turnage, RH
AF Khuri, SF
   Najjar, SF
   Daley, J
   Krasnicka, B
   Hossain, M
   Henderson, WG
   Aust, JB
   Bass, B
   Bishop, MJ
   Demakis, J
   DePalma, R
   Fabri, PJ
   Fink, A
   Gibbs, J
   Grover, F
   Hammermeister, K
   McDonald, G
   Neumayer, L
   Roswell, RH
   Spencer, J
   Turnage, RH
CA VA Natl Surgical Quality Improveme
TI Comparison of surgical outcomes between teaching and nonteaching
   hospitals in the Department of Veterans Affairs
SO ANNALS OF SURGERY
LA English
DT Article; Proceedings Paper
CT 121st Annual Meeting of the American-Surgical-Association
CY APR 26-28, 2001
CL COLORADO SPRINGS, COLORADO
SP Amer Surg Assoc
ID ACADEMIC MEDICAL-CENTERS; RISK ADJUSTMENT; POSTOPERATIVE MORBIDITY;
   CARE; QUALITY; MORTALITY; BENEFICIARIES; SEVERITY; PROGRAM; LENGTH
AB Objective To determine whether the investment in postgraduate education and training places patients at risk for worse outcomes and higher costs than if medical and surgical care was delivered in nonteaching settings.
   Summary Background Data The Veterans Health Administration (VA) plays a major role in the training of medical students, residents, and fellows.
   Methods The database of the VA National Surgical Quality Improvement Program was analyzed for all major noncardiac operations performed during fiscal years 1997, 1998, and 1999. Teaching status of a hospital was determined on the basis of a background and structure questionnaire that was independently verified by a research fellow. Stepwise logistic regression was used to construct separate models predictive of 30-day mortality and morbidity for each of seven surgical specialties and eight operations. Based on these models, a severity index for each patient was calculated, Hierarchical logistic regression models were then created to examine the relationship between teaching versus nonteaching hospitals and 30-day postoperative mortality and morbidity, after adjusting for patient severity.
   Results Teaching hospitals performed 81% of the total surgical workload and 90% of the major surgery workload. In most specialties in teaching hospitals, the residents were the primary surgeons in more than 90% of the operations. Compared with nonteaching hospitals, the patient populations in teaching hospitals had a higher prevalence of risk factors, underwent more complex operations, and had longer operation times. Risk-adjusted mortality rates were not different between the teaching and nonteaching hospitals in the specialties and operations studied. The unadjusted complication rate was higher in teaching hospitals in six of seven specialties and four of eight operations. Risk adjustment did not eliminate completely these differences, probably reflecting the relatively poor predictive validity of some of the risk adjustment models for morbidity. Length of stay after major operations was not consistently different between teaching and nonteaching hospitals.
   Conclusion Compared with nonteaching hospitals, teaching hospitals in the VA perform the majority of complex and high-risk major procedures, with comparable risk-adjusted 30-day mortality rates. Risk-adjusted 30-day morbidity rates in teaching hospitals are higher in some specialties and operations than in nonteaching hospitals. Although this may reflect the weak predictive validity of some of the risk adjustment models for morbidity, it may also represent suboptimal processes and structures of care that are unique to teaching hospitals. Despite good quality of care in teaching hospitals, as evidenced by the 30-day mortality data, efforts should be made to examine further the structures and processes of surgical care prevailing in these hospitals.
C1 VA Boston Healthcare Syst, Surg Serv, W Roxbury, MA 02132 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Brigham & Womens Hosp, Boston, MA 02115 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy,Partners HealthCare Syst, Boston, MA USA.
   Hines VA Cooperat Studies Program, Coordinating Ctr, Hines, IL USA.
   Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78284 USA.
   Univ Maryland, VA Maryland Hlth Care Syst, Baltimore, MD 21201 USA.
   Univ Washington, VA Puget Hlth Care Syst, Natl Anesthesia Serv, Seattle, WA 98195 USA.
   Dept Vet Affairs Headquarters, Hlth Serv Res & Dev Serv, Washington, DC USA.
   Univ S Florida, Coll Med, Tampa VA Med Ctr, Tampa, FL USA.
   Emory Univ, Sch Med, Atlanta, GA USA.
   Atlanta VA Med Ctr, Decatur, GA USA.
   Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO USA.
   Univ Utah, Med Ctr, VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA.
   Vet Integrated Serv Network 8, Bay Pines, FL USA.
   Univ Texas, SW Med Sch, VA N Texas Hlth Care Syst, Dallas, TX 75230 USA.
RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Surg Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA.
NR 34
TC 125
Z9 127
U1 1
U2 7
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 SEP
PY 2001
VL 234
IS 3
BP 370
EP 382
DI 10.1097/00000658-200109000-00011
PG 13
WC Surgery
SC Surgery
GA 470LH
UT WOS:000170873100020
PM 11524590
ER

PT J
AU Parsons, SK
   Fishman, SJ
   Hoorntje, LE
   Jaramillo, D
   Marcus, KC
   Perez-Atayde, AR
   Kozakewich, HP
   Grier, HE
   Shamberger, RC
AF Parsons, SK
   Fishman, SJ
   Hoorntje, LE
   Jaramillo, D
   Marcus, KC
   Perez-Atayde, AR
   Kozakewich, HP
   Grier, HE
   Shamberger, RC
TI Aggressive multimodal treatment of pleuropulmonary blastoma
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID PULMONARY BLASTOMA; MANAGEMENT; CHILDHOOD
AB Pleuropulmonary blastoma is a rare intrathoracic neoplasm almost solely confined to childhood. Survival is poor. The authors report 2 children with extensive intrathoracic disease who are long term survivors after multimodal therapy. Both children received multiagent neoadjuvant chemotherapy, followed by surgical resection to remove all gross tumor. Postoperative chemotherapy was given to both children; radiotherapy was also given in the second case because of a question of positive tumor margins. Experience supports the use of multimodal therapy, including an aggressive surgical approach in the potentially curative treatment of this tumor. (C) 2001 by The Society of Thoracic Surgeons.
C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
   Childrens Hosp, Dept Surg, Boston, MA 02115 USA.
   Childrens Hosp, Dept Radiol, Boston, MA 02115 USA.
   Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
   Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Parsons, SK (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
NR 8
TC 17
Z9 19
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 SEP
PY 2001
VL 72
IS 3
BP 939
EP 942
DI 10.1016/S0003-4975(00)02411-5
PG 4
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA 469LV
UT WOS:000170817900080
PM 11565696
ER

PT J
AU Rehring, TF
   Brewster, DC
   Kaufman, JA
   Fan, CM
   Geller, SC
AF Rehring, TF
   Brewster, DC
   Kaufman, JA
   Fan, CM
   Geller, SC
TI Regression of perianeurysmal fibrosis and ureteral dilation following
   endovascular repair of inflammatory abdominal aortic aneurysm
SO ANNALS OF VASCULAR SURGERY
LA English
DT Article
ID RETROPERITONEAL APPROACH; OBSTRUCTION
AB An inflammatory component to abdominal aortic aneurysms (AAA) is thought to occur in approximately 5% of cases. Accompanying ureteral entrapment may be involved in 20% of these. Transabdominal repair of inflammatory AAA with ureterolysis may result in increased complications. Many authorities have recommended a retroperitoneal approach to decrease dissection. Similarly, an endovascular approach has been utilized. We report here the results of a patient with an inflammatory AAA with bilateral ureteral obstruction successfully treated with endovascular stent graft repair and bilateral ureteral stents with exclusion of the aneurysm and resolution of hydronephrosis.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Radiol, Boston, MA USA.
RP Brewster, DC (reprint author), 1 Hawthorne Pl,Suite 111, Boston, MA 02114 USA.
NR 24
TC 13
Z9 14
U1 0
U2 0
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0890-5096
J9 ANN VASC SURG
JI Ann. Vasc. Surg.
PD SEP
PY 2001
VL 15
IS 5
BP 591
EP 593
DI 10.1007/s10016-001-0019-6
PG 3
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 479LA
UT WOS:000171404800017
PM 11665449
ER

PT J
AU Choi, CJ
   Nghiem, P
AF Choi, CJ
   Nghiem, P
TI Tacrolimus ointment in the treatment of chronic cutaneous graft-vs-host
   disease - A case series of 18 patients
SO ARCHIVES OF DERMATOLOGY
LA English
DT Article
ID ATOPIC-DERMATITIS; EXTRACORPOREAL PHOTOCHEMOTHERAPY; FK506;
   CYCLOSPORINE; PSORALEN; TRIAL; PUVA
AB Background: Tacrolimus (formerly FK 506) is an immunosuppressive drug that works by inhibiting calcineurin, a calcium-dependent protein phosphatase required for immune function. Tacrolimus has been shown to be effective topically in atopic dermatitis and systemically in psoriasis and graft-vs-host disease (GVHD). However, its efficacy in treating cutaneous GVHD when applied topically has not been reported.
   Objective: To assess the therapeutic efficacy of 0.1% tacrolimus ointment on chronic cutaneous GVHD in patients with symptoms refractory to systemic corticosteroid therapy.
   Results: Tacrolimus ointment effectively treated pruritus and/or erythema in 13 (72%) of 18 patients with chronic GVHD. Responding patients had a rapid effect within several hours to days. Effectiveness was measured by means of patient report, results of physical examination, side-by-side comparisons of tacrolimus vs a vehicle control, and temporal flares of the cutaneous symptoms of the disease in the context of stopping tacrolimus ointment therapy. Because of the progression of GVHD and in 2 cases, loss of drug efficacy, all patients eventually went on to receive more aggressive treatment, including increases in steroid dosage, psoralen-UV-A therapy, and extracorporeal photopheresis.
   Conclusions: This case series suggests that tacrolimus ointment has efficacy in treating the erythema and pruritus of steroid-refractory, chronic cutaneous GVHD in most patients, The rapid response of tacrolimus ointment may provide a useful therapeutic bridge to systemic therapies that have slower onset, such as psoralen-UV-A therapy or extracorporeal photopheresis.
C1 Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA.
   Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Nghiem, P (reprint author), Harvard Univ, Dept Chem & Biol Chem, 12 Oxford St, Cambridge, MA 02138 USA.
RI Nghiem, Paul/A-9210-2011
OI Nghiem, Paul/0000-0003-2784-963X
NR 25
TC 53
Z9 55
U1 0
U2 1
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 SEP
PY 2001
VL 137
IS 9
BP 1202
EP 1206
PG 5
WC Dermatology
SC Dermatology
GA 471RN
UT WOS:000170942600009
PM 11559218
ER

PT J
AU Salat, DH
   Kaye, JA
   Janowsky, JS
AF Salat, DH
   Kaye, JA
   Janowsky, JS
TI Selective preservation and degeneration within the prefrontal cortex in
   aging and Alzheimer disease
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID CEREBRAL-CORTEX; RHESUS-MONKEY; HIPPOCAMPAL-FORMATION; CORTICAL
   AFFERENTS; ENTORHINAL CORTEX; TEMPORAL-LOBE; GRAY-MATTER; IN-VIVO;
   VOLUME; PATHOLOGY
AB Background: The prefrontal cortex (PFC) is a heterogeneous cortical structure that supports higher cognitive functions, including working memory and verbal abilities. The PFC is vulnerable to neurodegeneration with healthy aging and Alzheimer disease (AD).
   Objective: We used volumetric magnetic resonance imaging to determine whether any region within the PFC is more vulnerable to deterioration with late aging or AD.
   Methods: Volumetric analysis of PFC regions was performed on younger healthy elderly subjects (n = 26; 14 men and 12 women [mean age, 71.7 years] for aging analysis; 12 men and 14 women [mean age, 71.4 years] for AD analysis), oldest healthy elderly (OHE) subjects (n = 22 [11 men and 11 women]; mean age, 88.9 years), and patients with AD (n=22 [12 men and 10 women]; mean age, 69.8 years).
   Results: The OHE subjects had less PFC white matter than did young healthy elderly subjects. The orbital region was selectively preserved relative to other PFC regions in the OHE subjects. Subjects with AD had less total PFC gray matter than did age-matched healthy subjects and significantly less volume in the inferior PFC region only.
   Conclusions: Orbital PFC is selectively preserved in OHE subjects. In contrast, degeneration within the PFC with AD is most prominent in the inferior PFC region. Thus, degeneration within the PFC has a regionally distinct pattern in healthy aging and AD.
C1 Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA.
   Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
   Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA.
RP Salat, DH (reprint author), Athinoula A Martinos Ctr, Dept Radiol, Bldg 149,13th St,Mail Code 149 2301, Charlestown, MA 02129 USA.
EM salat@nmr.mgh.harvard.edu
OI Kaye, Jeffrey/0000-0002-9971-3478
FU NIA NIH HHS [AG08017, AG12611]; NIMH NIH HHS [MH11855]
NR 28
TC 114
Z9 120
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD SEP
PY 2001
VL 58
IS 9
BP 1403
EP 1408
DI 10.1001/archneur.58.9.1403
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA 471RQ
UT WOS:000170942800008
PM 11559311
ER

PT J
AU Sukonick, DL
   Pollock, BG
   Sweet, RA
   Mulsant, BH
   Rosen, J
   Klunk, WE
   Kastango, KB
   DeKosky, ST
   Ferrell, RE
AF Sukonick, DL
   Pollock, BG
   Sweet, RA
   Mulsant, BH
   Rosen, J
   Klunk, WE
   Kastango, KB
   DeKosky, ST
   Ferrell, RE
TI The 5-HTTPR*S/*L polymorphism and aggressive behavior in Alzheimer
   disease
SO ARCHIVES OF NEUROLOGY
LA English
DT Article
ID SEROTONIN TRANSPORTER GENE; PROMOTER POLYMORPHISM; ALLELIC VARIATION;
   DEMENTIA; SUICIDE; REGION; ONSET; SUSCEPTIBILITY; EXPRESSION; DEPRESSION
AB Background: Aggressive behavior in Alzheimer disease (AD) has been linked to dysfunction of serotonin neurotransmission. Homozygosity for the long variant (*L) of an identified biallelic polymorphism of the serotonin transporter promoter region (5-HTTPR) is associated with increased expression of the transporter protein and increased speed of response to serotonin reuptake inhibitor treatment.
   Objective: To determine whether the *L/*L genotype and the *L allele are associated with an increased risk of aggressive symptoms in patients with AD.
   Design: Case-control study.
   Setting: University hospital geriatric psychiatry inpatient program and Alzheimer disease research center.
   Subjects: Fifty-eight patients with AD with a history of aggressive behavior and 79 never-aggressive patients with AD with comparable severity of cognitive impairment.
   Main Outcome Measures: The 5-HTTPR genotype and allele frequency.
   Results: The *L/*L genotype was significantly associated with aggression in patients with AD (odds ratio, 2.8; 95% confidence interval, 1.2-6.5). Similar results were obtained for *L allele frequency.
   Conclusion: The 5-HTTPR*L allele and *L/*L genotype may predispose patients with AD to develop aggressive behavior.
C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
   Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.
   Univ Pittsburgh, Dept Psychiat, Div Geriatr & Neuropsychiat, Pittsburgh, PA USA.
   Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
RP Sweet, RA (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA.
OI Klunk, William/0000-0001-5512-0251
FU NIA NIH HHS [AG05133]; NIMH NIH HHS [MH01603, MH01509, MH52247, MH59666]
NR 37
TC 59
Z9 59
U1 2
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610 USA
SN 0003-9942
J9 ARCH NEUROL-CHICAGO
JI Arch. Neurol.
PD SEP
PY 2001
VL 58
IS 9
BP 1425
EP 1428
DI 10.1001/archneur.58.9.1425
PG 4
WC Clinical Neurology
SC Neurosciences & Neurology
GA 471RQ
UT WOS:000170942800011
PM 11559314
ER

PT J
AU Silva, HCCR
   Coletta, RD
   Jorge, J
   Bolzani, G
   de Almeida, OP
   Graner, E
AF Silva, HCCR
   Coletta, RD
   Jorge, J
   Bolzani, G
   de Almeida, OP
   Graner, E
TI The effect of cyclosporin A on the activity of matrix metalloproteinases
   during the healing of rat molar extraction wounds
SO ARCHIVES OF ORAL BIOLOGY
LA English
DT Article
DE cyclosporin A; dental extraction; matrix metalloproteinases; wound
   healing; zymography
ID INDUCED GINGIVAL OVERGROWTH; TOOTH EXTRACTION; FIBROBLASTS; EXPRESSION;
   GROWTH; MMP-1
AB Cyclosporin A (CyA) is a cyclic peptide used as an immunosuppressive agent because it can block the synthesis of interleukin-2 and other cytokines produced by CD4+ lymphocytes. It is widely used for the prevention of allograft rejection and treatment of autoimmune diseases. Several side-effects of CyA treatment have been reported, among which are chronic nephrotoxicity, hepatotoxicity and neurotoxicity, lymphoproliferative neoplasms, hypertension, thromboembolic complications and gingival overgrowth. Here, using a rat molar model, it is demonstrated that CyA immunosuppression inhibits the activity of matrix metalloproteinases 2 and 9 in the early phase of granulation tissue in the healing dental socket. These observations suggest that CyA may interfere with the wound healing following dental extractions. (C) 2001 Elsevier Science Ltd. All rights reserved.
C1 UNICAMP, Dept Oral Pathol & Genet, Sch Dent Piracicaba, BR-13414018 Piracicaba, SP, Brazil.
RP Graner, E (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Room D-742,44 Binney St, Boston, MA 02115 USA.
RI Graner, Edgard/K-4411-2012; Coletta, Ricardo/B-4909-2015
OI Coletta, Ricardo/0000-0001-5285-3046
NR 28
TC 16
Z9 16
U1 2
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0003-9969
J9 ARCH ORAL BIOL
JI Arch. Oral Biol.
PD SEP
PY 2001
VL 46
IS 9
BP 875
EP 879
DI 10.1016/S0003-9969(01)00045-0
PG 5
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 463DT
UT WOS:000170462100012
PM 11420061
ER

PT J
AU Kenna, MA
   Wu, BL
   Cotanche, DA
   Korf, BR
   Rehm, HL
AF Kenna, MA
   Wu, BL
   Cotanche, DA
   Korf, BR
   Rehm, HL
TI Connexin 26 studies in patients with sensorineural hearing loss
SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article; Proceedings Paper
CT 15th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology
CY MAY 16-19, 2000
CL ORLANDO, FLORIDA
SP Amer Soc Pediat Otolaryngol
ID CHILDHOOD DEAFNESS; GENE GJB2; GAP-JUNCTIONS; MUTATIONS; IMPAIRMENT;
   JAPANESE
AB Objective: To determine the spectrum of connexin 26 (Cx26) mutations and their phenotypes in children with sensorineural hearing loss (SNHL) or mixed hearing loss (MHL).
   Design: Children with SNHL or MHL were prospectively tested for mutations in the entire coding region of the Cx26 gene.
   Patients: Children with SNHL or MHL with no obvious etiology for the hearing loss.
   Results: Between December 1, 1998, and July 1, 2000, 107 patients with SNHL or MHL from 99 families underwent Cx26 testing. Most patients were aged 1 week to 16 years (61 boys and 46 girls). Thirty (30%) of 99 probands had Cx26 mutations: biallelic mutations were detected in 18 (9 homozygous and 9 compound heterozygous) and single mutations were detected in 12. Twelve previously reported mutations (35delG, 167delT, E47X, L90P, M34T, G12V, V37I, R143W, V84L, V153I, V27I, and 310del14) and 3 novel mutations (E129K, T8M, and N206S) were found. Hearing loss in patients with biallelic Cx26 mutations ranged from unilateral high frequency to bilateral profound. Four children, 2 with biallelic mutations, had temporal bone abnormalities.
   Conclusions: Connexin 26 mutations are common in children with SNHL, and it is likely that the homozygous and compound heterozygous mutations cause the SNHL. However, pathogenicity is less certain where only a single Cx26 mutation is present. Patients with biallelic Cx26 mutations had a slightly higher incidence of milder hearing loss than ire previous studies. Children with SNHL or MHL should be tested for Cx26 mutations early in their evaluation.
C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
   Childrens Hosp, Dept Otolaryngol & Commun Disorders, Boston, MA 02115 USA.
   Childrens Hosp, Genet Diagnost Lab, Boston, MA 02115 USA.
   Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA.
   Childrens Hosp, Lab Cellular & Mol Hearing Res, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners Ctr Human Genet, Boston, MA USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA USA.
RP Kenna, MA (reprint author), Childrens Hosp, Dept Otolaryngol, 300 Longwood Ave, Boston, MA 02115 USA.
OI Cotanche, Douglas/0000-0001-7972-0446
NR 25
TC 102
Z9 108
U1 0
U2 1
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 SEP
PY 2001
VL 127
IS 9
BP 1037
EP 1042
PG 6
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 471XK
UT WOS:000170953800001
PM 11556849
ER

PT J
AU Bhattacharyya, N
   Vyas, DK
   Fechner, FP
   Gliklich, RE
   Metson, R
AF Bhattacharyya, N
   Vyas, DK
   Fechner, FP
   Gliklich, RE
   Metson, R
TI Tissue eosinophilia in chronic sinusitis - Quantification techniques
SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID EXPRESSION
AB Objective: To ascertain the reliability of a proposed method for quantifying tissue eosinophilia in sinus mucosa.
   Design: Prospective cohort study.
   Interventions and Outcome Measures: Pathology slides from patients undergoing endoscopic sinus surgery for chronic rhinosinusitis were independently assessed by 2 reviewers. Using a proposed systematic counting method, the degree of tissue eosinophilia was quantified. Disease severity was assessed by computed tomographic (CT) staging. Intrarater, interrater, and intrapatient reliability was determined using correlational reliability analysis. The degree of correlation between tissue eosinophilia and CT stage was determined.
   Results: One hundred thirty-two slides from 65 patients were reviewed. The mean (SD) eosinophil density was 23.4 (37.2) eosinophils per high-power field. Only 12 patients (18%) had no eosinophils on histopathologic analysis. Strong intrarater (r greater than or equal to0.91 for each rater, P<.001) and interrater reliability (r<greater than or equal to>0.82 between raters, P<.001) was noted for the quantification method. A moderate degree of correlation was found between CT scan stage and degree of tissue eosinophilia (Spearman <rho>=0.62, P<.001).
   Conclusions: The proposed method for quantifying tissue eosinophilia in sinus mucosa is reliable and valid. A relatively strong correlation exists between CT scan stage and tissue eosinophilia in chronic rhinosinusitis.
C1 Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02114 USA.
   Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol, 333 Longwood Ave, Boston, MA 02114 USA.
NR 11
TC 31
Z9 34
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60610 USA
SN 0886-4470
J9 ARCH OTOLARYNGOL
JI Arch. Otolaryngol. Head Neck Surg.
PD SEP
PY 2001
VL 127
IS 9
BP 1102
EP 1105
PG 4
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA 471XK
UT WOS:000170953800013
PM 11556861
ER

PT J
AU Scully, RE
   Antman, KH
AF Scully, RE
   Antman, KH
CA Coll Amer Pathologists Members Can
TI Protocol for the examination of specimens from patients with tumors of
   the peritoneum - A basis for checklists
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID SEROUS BORDERLINE TUMORS; CARCINOMA; OVARY; WOMEN
C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA.
   Columbia Presbyterian Med Ctr, Div Med Oncol, New York, NY 10032 USA.
RP Scully, RE (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA.
NR 12
TC 1
Z9 1
U1 0
U2 0
PU COLLEGE AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD SEP
PY 2001
VL 125
IS 9
BP 1174
EP 1176
PG 3
WC Medical Laboratory Technology; Medicine, Research & Experimental;
   Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
   Pathology
GA 472EQ
UT WOS:000170970900006
PM 11520266
ER

PT J
AU Weiler, H
   Lindner, V
   Kerlin, B
   Isermann, BH
   Hendrickson, SB
   Cooley, BC
   Meh, DA
   Mosesson, MW
   Shworak, NW
   Post, MJ
   Conway, EM
   Ulfman, LH
   von Andrian, UH
   Weitz, JI
AF Weiler, H
   Lindner, V
   Kerlin, B
   Isermann, BH
   Hendrickson, SB
   Cooley, BC
   Meh, DA
   Mosesson, MW
   Shworak, NW
   Post, MJ
   Conway, EM
   Ulfman, LH
   von Andrian, UH
   Weitz, JI
TI Characterization of a mouse model for thrombomodulin deficiency
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE transgenic mice; thrombomodulin; thrombosis; inflammation; thrombosis
   modifier genes
ID ACTIVATED PROTEIN-C; HUMAN MONONUCLEAR PHAGOCYTES;
   MYOCARDIAL-INFARCTION; ESCHERICHIA-COLI; CAROTID-ARTERY; SOLUBLE
   THROMBOMODULIN; THROMBOEMBOLIC-DISEASE; NEOINTIMA FORMATION;
   ANTITHROMBIN-III; GENE-MUTATIONS
AB Mutations in the gene encoding thrombomodulin (TM), a thrombin regulator, are suspected risk factors for venous and arterial thrombotic disease. We have previously described the generation of TMPro/Pro mice carrying a TM gene mutation that disrupts the TM-dependent activation of protein C. Here, it is shown that inbred C57BL/6J TMPro/Pro mice exhibit a hypercoagulable state and an increased susceptibility to thrombosis and sepsis. Platelet thrombus growth after FeCl3-induced acute endothelial injury was accelerated in mutant mice. Vascular stasis after permanent ligation of the carotid artery precipitated thrombosis in mutant but not in normal mice. Mutant mice showed increased mortality after exposure to high doses of endotoxin and demonstrated altered cytokine production in response to low-dose endotoxin. The severity of the hypercoagulable state and chronic microvascular thrombosis caused by the TMPro mutation is profoundly influenced by mouse strain-specific genetic differences between C57BL/6 and 129SvPas mice. These data demonstrate that in mice, TM is a physiologically relevant regulator of platelet- and coagulation-driven large-vessel thrombosis and modifies the response to endotoxin-induced inflammation. The phenotypic penetrance of the TMPro mutation is determined by as-yet-uncharacterized genetic modifiers of thrombosis other than TM.
C1 Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53226 USA.
   Blood Res Inst, Milwaukee, WI USA.
   Maine Med Ctr, Res Inst, Portland, ME 04102 USA.
   Beth Israel Deaconess Med Ctr, Div Cardiovasc, Angiogenesis Res Ctr, Boston, MA 02215 USA.
   Univ Leuven VIB, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium.
   Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   McMaster Univ, Hamilton, ON, Canada.
   Hamilton Civ Hosp, Res Ctr, Hamilton, ON, Canada.
   Med Coll Wisconsin, Milwaukee, WI 53226 USA.
RP Weiler, H (reprint author), Blood Ctr SE Wisconsin Inc, Blood Res Inst, 8727 Watertown Plank Rd, Milwaukee, WI 53226 USA.
EM hweiler@besew.edu
RI von Andrian, Ulrich/A-5775-2008; Kerlin, Bryce/E-3369-2011; 
OI Kerlin, Bryce/0000-0002-1756-8271; Conway, Edward/0000-0003-0081-0305
FU NHLBI NIH HHS [HL-60655, HL-62524, HL-62572, HL54936]
NR 43
TC 104
Z9 108
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD SEP
PY 2001
VL 21
IS 9
BP 1531
EP 1537
DI 10.1161/hq0901.094496
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 472RW
UT WOS:000170999600026
PM 11557684
ER

PT J
AU Russo, GT
   Meigs, JB
   Cupples, LA
   Demissie, S
   Otvos, JD
   Wilson, PWF
   Lahoz, C
   Cucinotta, D
   Couture, P
   Mallory, T
   Schaefer, EJ
   Ordovas, JM
AF Russo, GT
   Meigs, JB
   Cupples, LA
   Demissie, S
   Otvos, JD
   Wilson, PWF
   Lahoz, C
   Cucinotta, D
   Couture, P
   Mallory, T
   Schaefer, EJ
   Ordovas, JM
TI Association of the Sst-I polymorphism at the APOC3 gene locus with
   variations in lipid levels, lipoprotein subclass profiles and coronary
   heart disease risk: the Framingham offspring study
SO ATHEROSCLEROSIS
LA English
DT Article
DE apoC3; triglycerides; polymorphisms; lipoprotein particle size; insulin
   resistance
ID APOLIPOPROTEIN-C-III; HIGH-DENSITY-LIPOPROTEIN; FAMILIAL COMBINED
   HYPERLIPIDEMIA; INSULIN-RESPONSE ELEMENT; CIII GENE; A-I; DNA
   POLYMORPHISMS; ARTERY DISEASE; PLASMA-LIPOPROTEINS; JAPANESE POPULATION
AB Apolipoprotein (apo) CIII participates in the regulation of the metabolism of triglyceride-rich lipoproteins and it is a major component of chylomicrons and VLDL. The APOC3 gene is on chromosome 11q23 and is highly polymorphic. The less common allele (S2) of the SstI polymorphism on the 3' untranslated region of the APOC3 gene has been previously associated with increased triglycerides, total cholesterol (TC), and apoCIII levels and cardiovascular risk on several, but not all, studies. The aim of this study was to examine the association of this polymorphism with plasma lipid levels, lipoprotein subfractions and coronary heart disease (CHD) risk in a population-based study: The Framingham Offspring Study. The frequency of the S2 allele was 0.086, consistent with previous reports in Caucasian populations. In men, the S2 allele was associated with lower concentrations of high-density lipoprotein cholesterol (HDL-C; P < 0.04) and HDL2-C (P < 0.02) and a significant increase in apoCIII non-HDL (P < 0.05). TG levels were higher in men carriers of the S2 allele, but this association did not reach statistical significance (P = 0.30). Conversely, in women, the S2 allele was associated with increased TC (P < 0.03), low-density lipoprotein cholesterol (LDL-C; P < 0.03), and ApoB levels (P < 0.04). Lipoproteins subfractions were also examined using nuclear magnetic resonance (NMR) spectroscopy. S2 male carriers had significantly lower concentrations of large LDL and a significant reduction in LDL particle size (P < 0.04). In women, there was a significant increase in intermediate LDL particles (P < 0.05) with no significant effect on lipoprotein diameters. We also examined the associations between the S2 allele and biochemical markers of glucose metabolism. In men, the S2 allele was associated with elevated fasting insulin concentrations (P < 0.04), whereas no significant associations were observed in women. Despite the described associations with lipid and glucose metabolism related risk factors, we did not find any significant increase in CHD risk associated with the S2 allele in this population. ((C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
C1 Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Lipid Metab Lab, Boston, MA 02111 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   N Carolina State Univ, Boston Univ, Sch Publ Hlth, Raleigh, NC 27695 USA.
   N Carolina State Univ, Dept Biochem, Raleigh, NC 27695 USA.
   NHLBI, Framingham Heart Study, Framingham, MA 01701 USA.
   Univ Messina, Dept Internal Med, Messina, Italy.
   Wako Diagnost, Richmond, VA USA.
RP Ordovas, JM (reprint author), Tufts Univ, USDA, Jean Mayer Human Nutr Res Ctr Aging, Lipid Metab Lab, 711 Washington St, Boston, MA 02111 USA.
RI cucinotta, domenico/F-4832-2014; 
OI Ordovas, Jose/0000-0002-7581-5680
FU NHLBI NIH HHS [HL54776, HL35243, N01 HL38038]
NR 67
TC 86
Z9 90
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 SEP
PY 2001
VL 158
IS 1
BP 173
EP 181
DI 10.1016/S0021-9150(01)00409-9
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 466YK
UT WOS:000170673600022
PM 11500189
ER

PT J
AU Fals-Stewart, W
   O'Farrell, TJ
   Hooley, JM
AF Fals-Stewart, W
   O'Farrell, TJ
   Hooley, JM
TI Relapse among married or cohabiting substance-abusing patients: The role
   of perceived criticism
SO BEHAVIOR THERAPY
LA English
DT Article
ID EXPRESSED EMOTION; DYADIC ADJUSTMENT; DRUG-ABUSE; THERAPY; ALCOHOLISM;
   BEHAVIOR; PARTNERS; VALIDITY; COUPLES
AB The purpose of the present investigation was to examine the contribution of perceived criticism (PC) to the prediction of relapse among married or cohabiting heterosexual male substance-abusing patients (N = 106) entering outpatient treatment. After controlling for sociodemographic variables and substance abuse problem severity, higher levels of patients' PC by their spouses were significantly associated with greater likelihood of relapse, fewer days abstinent, and shorter time to relapse. PC continued to make a significant unique contribution to relapse variables even when level of relationship satisfaction was also controlled.
C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
   VA Boston Healthcare Syst, Boston, MA USA.
   SUNY Buffalo, Buffalo, NY 14260 USA.
RP Fals-Stewart, W (reprint author), Res Inst Addict, 1021 Main St, Buffalo, NY 14203 USA.
RI Hooley, Jill/A-3945-2013
OI Hooley, Jill/0000-0002-1162-3540
NR 29
TC 35
Z9 35
U1 0
U2 2
PU ASSOC ADV BEHAVIOR THERAPY
PI NEW YORK
PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA
SN 0005-7894
J9 BEHAV THER
JI Behav. Therapy
PD FAL
PY 2001
VL 32
IS 4
BP 787
EP 801
DI 10.1016/S0005-7894(01)80021-6
PG 15
WC Psychology, Clinical
SC Psychology
GA 542YE
UT WOS:000175072600011
ER

PT J
AU Miller, MW
   Patrick, CJ
AF Miller, MW
   Patrick, CJ
TI Trait differences in affective and attentional responding to threat
   revealed by emotional stroop interference and startle reflex modulation
SO BEHAVIOR THERAPY
LA English
DT Article
ID FEAR-POTENTIATED STARTLE; INDIVIDUAL-DIFFERENCES; SOCIAL PHOBIA;
   ANXIETY; EYEBLINK; STIMULI; STRESS; PROBE; INFORMATION; PSYCHOPATH
AB This study utilized startle reflex and reaction time (RT) measures to examine the hypothesis that anxious individuals exhibit an attentional bias for threatening information. High and low trait-anxious (HTA; LTA) participants performed an emotional Stroop task in which pleasant, neutral, and threat words were presented under conditions of anticipation, or no anticipation, of electric shock. Acoustic startle probes were presented during the interval between word presentation and production of the color-naming response. HTA participants showed longer color-naming RT for threat words than pleasant words under both shock anticipation and safe conditions of the procedure. Under safe conditions, startle patterns paralleled these effects with HTA participants exhibiting smaller blink responses - indicating greater allocation of processing resources - for threat words than pleasant words. Under shock anticipation conditions, HTA individuals showed an opposite response pattern: startle blinks were potentiated for threat words relative to pleasant, indicating that the emotional impact of the threat words was enhanced by the aversive mood state. Despite evidence that the startle response effects were limited by habituation to the first half (ISO trials) of the procedure, these findings support the hypothesis that HTA individuals possess an attentional bias for threatening information and exhibit greater defensive emotional reactivity to threat cues during states of heightened negative affectivity than low anxious individuals.
C1 Florida State Univ, Tallahassee, FL 32306 USA.
   Univ Minnesota, Minneapolis, MN 55455 USA.
RP Miller, MW (reprint author), Boston VA Med Ctr, Natl Ctr PTSD, 150 S Huntington Ave, Boston, MA 02130 USA.
RI Miller, Mark/G-7322-2011
OI Miller, Mark/0000-0001-6393-8563
NR 54
TC 3
Z9 3
U1 3
U2 10
PU ASSOC ADV BEHAVIOR THERAPY
PI NEW YORK
PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA
SN 0005-7894
J9 BEHAV THER
JI Behav. Therapy
PD FAL
PY 2001
VL 31
IS 4
BP 757
EP 776
PG 20
WC Psychology, Clinical
SC Psychology
GA 473VG
UT WOS:000171068600011
ER

PT J
AU Cook, RJ
   Brumback, BB
   Wigg, MB
   Ryan, LM
AF Cook, RJ
   Brumback, BB
   Wigg, MB
   Ryan, LM
TI Synthesis of evidence from epidemiological studies with
   interval-censored exposure due to grouping
SO BIOMETRICS
LA English
DT Article
DE dose-response effect; exposure variable; interval censoring;
   meta-analysis; polychotomous logistic regression
ID DOSE-RESPONSE DATA; LIMB REDUCTION DEFECTS; PRENATAL-DIAGNOSIS;
   FOLLOW-UP; VILLUS; METAANALYSIS; AMNIOCENTESIS; EXPERIENCE;
   ABNORMALITIES; ANOMALIES
AB We describe a method for assessing dose-response effects from a series of case-control and cohort studies in which the exposure information is interval censored. The interval censoring of the exposure variable is dealt with through the use of retrospective models in which the exposure is treated as a multinomial response and disease status as a binary covariate. Polychotomous logistic regression models are adopted in which the dose-response relationship between exposure and disease may be modeled in a discrete or continuous fashion. Partial conditioning is possible to eliminate some of the nuisance parameters. The methods are applied to the motivating study of the relationship between chorionic villus sampling and the occurrence of terminal transverse limb reduction.
C1 Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada.
   Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
   Harvard Univ, Sch Publ Hlth, Dept Biostat, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Cook, RJ (reprint author), Univ Waterloo, Dept Stat & Actuarial Sci, 200 Univ Ave W, Waterloo, ON N2L 3G1, Canada.
RI Ryan, Louise/A-4562-2009
OI Ryan, Louise/0000-0001-5957-2490
FU NCI NIH HHS [CA-48061]; NICHD NIH HHS [HD-33222]
NR 48
TC 6
Z9 6
U1 0
U2 0
PU INTERNATIONAL BIOMETRIC SOC
PI WASHINGTON
PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD SEP
PY 2001
VL 57
IS 3
BP 671
EP 680
DI 10.1111/j.0006-341X.2001.00671.x
PG 10
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology; Mathematics
GA 467YY
UT WOS:000170732400002
PM 11550914
ER

PT J
AU Xu, RH
   Harrington, DP
AF Xu, RH
   Harrington, DP
TI A semiparametric estimate of treatment effects with censored data
SO BIOMETRICS
LA English
DT Article
DE average regression effect; estimating equation; G(rho) family;
   Kaplan-Meier estimate; time-varying effects model; transformation models
ID MAXIMUM-LIKELIHOOD-ESTIMATION; PROPORTIONAL HAZARDS MODEL;
   SURVIVAL-DATA; ODDS MODEL; REGRESSION; HETEROGENEITY; INFERENCE
AB A semiparametric estimate of an average regression effect with right-censored failure time data has recently been proposed under the Cox-type model where the regression effect beta (t) is allowed to vary with time. In this article, we derive a simple algebraic relationship between this average regression effect and a measurement of group differences in k-sample transformation models when the random error belongs to the GP family of Harrington and Fleming (1982, Biometrika 69, 553 566), the latter being equivalent to the conditional regression effect in a gamma frailty model. The models considered here are suitable for the attenuating hazard ratios that often arise in practice. The results reveal ail interesting connection among the above three classes of models as alternatives to the proportional hazards assumption and add to our understanding of the behavior of the partial likelihood estimate under nonproportional hazards. The algebraic relationship provides a simple estimator under the transformation model. We develop a variance estimator based on the empirical influence function that is much easier to compute than the previously suggested resampling methods. When there is truncation in the right tail of the failure times, we propose a method of bias correction to improve the coverage properties of the confidence intervals. The estimate, its estimated variance, and the bias correction term call all be calculated with minor modifications to standard software for proportional hazards regression.
C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Xu, RH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
FU NCI NIH HHS [CA39929]
NR 36
TC 8
Z9 8
U1 0
U2 2
PU INTERNATIONAL BIOMETRIC SOC
PI WASHINGTON
PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD SEP
PY 2001
VL 57
IS 3
BP 875
EP 885
DI 10.1111/j.0006-341X.2001.00875.x
PG 11
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology; Mathematics
GA 467YY
UT WOS:000170732400028
PM 11550940
ER

PT J
AU Schoenfeld, DA
AF Schoenfeld, DA
TI A simple algorithm for designing group sequential clinical trials
SO BIOMETRICS
LA English
DT Article
DE acute respiratory distress syndrome; clinical trials; futility stopping
   rules; group sequential designs; hypothesis test; numerical integration
ID BOUNDARIES
AB This article describes a simple algorithm for calculating probabilities associated with group sequential trials. This allows the choice of boundaries that may not be among those implemented in available software.
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Schoenfeld, DA (reprint author), Massachusetts Gen Hosp, 50 Staniford St, Boston, MA 02114 USA.
FU NCI NIH HHS [CA-78784]; NHLBI NIH HHS [HR-46064]
NR 13
TC 9
Z9 9
U1 0
U2 0
PU INTERNATIONAL BIOMETRIC SOC
PI WASHINGTON
PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA
SN 0006-341X
J9 BIOMETRICS
JI Biometrics
PD SEP
PY 2001
VL 57
IS 3
BP 972
EP 974
DI 10.1111/j.0006-341X.2001.00972.x
PG 3
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology; Mathematics
GA 467YY
UT WOS:000170732400040
PM 11550952
ER

PT J
AU Kuter, DJ
   Goodnough, LT
   Romo, J
   DiPersio, J
   Peterson, R
   Tomita, D
   Sheridan, W
   McCullough, J
AF Kuter, DJ
   Goodnough, LT
   Romo, J
   DiPersio, J
   Peterson, R
   Tomita, D
   Sheridan, W
   McCullough, J
TI Thrombopoietin therapy increases platelet yields in healthy platelet
   donors
SO BLOOD
LA English
DT Article
ID HUMAN MEGAKARYOCYTE GROWTH; TRANSFUSION MEDICINE; ADVANCED CANCER; 2
   PARTS; BLOOD; CHEMOTHERAPY; COLLECTION; CYTOKINE; RECEPTOR; PROGRESS
AB The recombinant thrombopoietins have been shown to be effective stimulators of platelet production in cancer patients. It was therefore of interest to determine if one of these, pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), could be used to increase platelet counts and consequently platelet yields from apheresis in healthy platelet donors. In a blinded, 2-cycle, crossover study, 59 platelet donors were randomized to receive a single subcutaneous injection of PEG-rHuMGDF (1 mug/kg or 3 mug/kg) or placebo and 15 days later undergo platelet apheresis. Donors treated with placebo had a median peak platelet count after PEG-rHuMGDF injection of 248 x 10(9)/L compared with 366 x 10(9)/L in donors treated with 11 mug/kg PEG-rHuMGDF and 602 x 10(9)/L in donors treated with 3 mug/kg PEG-rHuMGDF. The median maximum percentage that platelet counts increased from baseline was 10% in donors who received placebo compared with 70% in donors who received 1 mug/kg and 167% in donors who received 3 mug/kg PEG-rHuMGDF. There was a direct relationship between the platelet yield and the preapheresis platelet count: Placebo-treated donors provided 3.8 x 10(11) (range 1.3 x 10(11)-7.9 x 1011) platelets compared with 5.6 x 10(11) (range 2.6 x 10(11)-12.5 x 10(11)) or 11.0 x 10(11) (range 7.1 x 10(11)-18.3 x 10(11)) in donors treated with I mug/kg or 3 mug/kg PEG-rHuMGDF, respectively. Substandard collections (<3 x 10(11) platelets) were obtained from 26%, 4%, and 0% of the placebo, 1 mug/kg, and 3 mug/kg donors, respectively. No serious adverse events were reported; nor were there events that met the criteria for dose-limiting toxicity. Thrombopoietin therapy can increase platelet counts in healthy donors to provide a median 3-fold more apheresis platelets compared with untreated donors. (C) 2001 by The American Society of Hematology.
C1 Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA.
   Washington Univ, St Louis, MO USA.
   Univ Minnesota, Minneapolis, MN USA.
   Amgen Inc, Thousand Oaks, CA USA.
RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, COX 640,100 Blossom St, Boston, MA 02114 USA.
FU NHLBI NIH HHS [HL54838]
NR 29
TC 56
Z9 58
U1 1
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 1
PY 2001
VL 98
IS 5
BP 1339
EP 1345
DI 10.1182/blood.V98.5.1339
PG 7
WC Hematology
SC Hematology
GA 467DH
UT WOS:000170685000012
PM 11520780
ER

PT J
AU Goodnough, LT
   Kuter, DJ
   McCullough, J
   Slichter, SJ
   DiPersio, J
   Romo, J
   Peterson, R
   Smith, KJ
   Raife, T
   Tomita, D
   Armstrong, S
AF Goodnough, LT
   Kuter, DJ
   McCullough, J
   Slichter, SJ
   DiPersio, J
   Romo, J
   Peterson, R
   Smith, KJ
   Raife, T
   Tomita, D
   Armstrong, S
TI Prophylactic platelet transfusions from healthy apheresis platelet
   donors undergoing treatment with thrombopoietin
SO BLOOD
LA English
DT Article
ID COLONY-STIMULATING FACTOR; HUMAN MEGAKARYOCYTE GROWTH; BLOOD STEM-CELLS;
   PERIPHERAL-BLOOD; NORMAL INDIVIDUALS; EMERGING ISSUES; TRANSPLANTATION;
   COLLECTION; THERAPY; COUNTS
AB Many patients receiving dose-intensive chemotherapy acquire thrombocytopenia and need platelet transfusions. A study was conducted to determine whether platelets harvested from healthy donors treated with thrombopoietin could provide larger increases In platelet counts and thereby delay time to next platelet transfusion compared to routinely available platelets given to thrombocytopenic patients. Community platelet donors received either 1 or 3 mug/kg pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) or placebo and then donated platelets 10 to 15 days later. One hundred sixty-six of these platelet concentrates were then transfused to 120 patients with platelets counts 25 x 10(9)/L or lower. Pretransfusion platelet counts (11 x 10(9)/L) were similar for recipients of placebo-derived and PEG-rHuMGDF-derived platelets. Early after transfusion, the median platelet count increment was higher In patients receiving PEG-rHuMGDF-derived platelets: 19 (range, -12-66) x 10(9)/L, 41 (range, 5-133) x 10(9)/L, and 82 (range, -4-188) x 10(9)/L for placebo-, 1-mug/kg-, and 3-mu /kg-derived platelets, respectively. This difference was maintained 18 to 24 hours after transfusion. Transfusion-free Intervals were 1.72, 2.64, and 3.80 days for the recipients of the placebo-, 1-mug/kg-, and 3-mu /kg-derived platelets, respectively. The rate of transfusion-related adverse events was not different In recipients of placebo-derived and PEG-rHuMGDF-derived platelets. Therefore, when transfused Into patients with thrombocytopenia, platelets collected from healthy donors undergoing thrombopoietin therapy were safe and resulted In significantly greater platelet count increments and longer transfusion-free intervals than platelets obtained from donors treated with placebo. (C) 2001 by The American Society of Hematology.
C1 Washington Univ, Sch Med, Dept Pathol & Med, St Louis, MO 63110 USA.
   Massachusetts Gen Hosp, Dept Pathol & Med, Boston, MA 02114 USA.
   Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA.
   Univ Washington, Sch Med, Seattle, WA 98195 USA.
   Puget Sound Blood Ctr, Seattle, WA 98104 USA.
   Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA.
   Blood Ctr SE Wisconsin Inc, Milwaukee, WI 53233 USA.
   Amgen Inc, Thousand Oaks, CA USA.
RP Goodnough, LT (reprint author), Washington Univ, Sch Med, Dept Pathol & Med, Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA.
NR 24
TC 63
Z9 66
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 SEP 1
PY 2001
VL 98
IS 5
BP 1346
EP 1351
DI 10.1182/blood.V98.5.1346
PG 6
WC Hematology
SC Hematology
GA 467DH
UT WOS:000170685000013
PM 11520781
ER

PT J
AU Methia, N
   Andre, P
   Denis, CV
   Economopoulos, M
   Wagner, DD
AF Methia, N
   Andre, P
   Denis, CV
   Economopoulos, M
   Wagner, DD
TI Localized reduction of atherosclerosis in von Willebrand
   factor-deficient mice
SO BLOOD
LA English
DT Article
ID LATE ANTIGEN-4 INTEGRIN; FATTY STREAK FORMATION; LAMINAR SHEAR-STRESS;
   P-SELECTIN; ENDOTHELIAL-CELLS; VONWILLEBRAND DISEASE; DIET; ARTERIOLES;
   MECHANISMS; EXPRESSION
AB To examine the role of the platelet adhesion molecule von Willebrand factor (vWf) In atherogenesis, vWf-deficient mice (vWf-/-) were bred with mice lacking the low-density lipoprotein receptor (LDLR-/-) on a C57BL/6J background. LDLR-/-vWf+/+ and LDLR-/-vWf-/- mice were placed on a diet rich In saturated fat and cholesterol for different lengths of time. The atherogenic diet stimulated leukocyte rolling in the mesenteric venules in both genotypes, Indicating an Increase in P-selectin-mediated adhesion to the endothelium. After 8 weeks on the atherogenic diet, the fatty streaks formed in the aortic sinus of LDLR -/-vWf-/- mice of either sex were 40% smaller and contained fewer monocytes than those In LDLR-/-vWf+/+ mice. After 22 weeks on the atherogenic diet (early fibrous plaque stage), the difference In lesion size in the aortic sinus persisted. Interestingly, the lesion distribution in the aortas of LDLR-/-vWf-/- animals was different from that of LDLR-/-vWf+/+ animals. In vWf-positive mice, half of all lesions were located at the branch points of the renal and mesenteric arteries, whereas lesions in this area were not as prominent In the vWf-negative mice. These results indicate that the absence of vWf primarily affects the regions of the aorta with disturbed flow that are prone to atherosclerosis. Thus, vWf may recruit platelets/leukocytes to the lesion in a flow-dependent manner or may be part of the mechano-transduction pathway regulating endothelial response to shear stress. (C) 2001 by The American Society of Hematology.
C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA.
RI Denis , Cecile/A-7649-2011
OI Denis , Cecile/0000-0001-5152-9156
FU NHLBI NIH HHS [R01 HL041002, R37 HL41002]
NR 41
TC 105
Z9 107
U1 0
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA
SN 0006-4971
J9 BLOOD
JI Blood
PD SEP 1
PY 2001
VL 98
IS 5
BP 1424
EP 1428
DI 10.1182/blood.V98.5.1424
PG 5
WC Hematology
SC Hematology
GA 467DH
UT WOS:000170685000023
PM 11520791
ER

PT J
AU Kiani, A
   Garcia-Cozar, FJ
   Habermann, I
   Laforsch, S
   Aebischer, T
   Ehninger, G
   Rao, A
AF Kiani, A
   Garcia-Cozar, FJ
   Habermann, I
   Laforsch, S
   Aebischer, T
   Ehninger, G
   Rao, A
TI Regulation of interferon-gamma gene expression by nuclear factor of
   activated T cells
SO BLOOD
LA English
DT Article
ID TRANSCRIPTION FACTOR NFAT1; NF-KAPPA-B; FUNCTIONAL-CHARACTERIZATION;
   INTERLEUKIN-3 LOCUS; LEISHMANIA-MAJOR; BINDING PROTEIN; TH1 DEVELOPMENT;
   CYCLOSPORINE-A; NATURAL-KILLER; DEFICIENT MICE
AB Transcription factors of the nuclear factor of activated T cells (NFAT) family are thought to regulate the expression of a variety of inducible genes such as Interleukin-2 (IL-2), IL-4, and tumor necrosis factor-alpha. However, It remains unresolved whether NFAT proteins play a role In regulating transcription of the Interferon-gamma (IFN-gamma) gene. Here it is shown that the transcription factor NFAT1 (NFATc2) is a major regulator of IFN-gamma production in vivo. Compared with T cells expressing NFAT1, T cells lacking NFAT1 display a substantial IL-4-independent defect in expression of IFN-gamma mRNA and protein. Reduced IFN-gamma production by NFAT1(-/-)x IL-4(-/-) T cells is observed after primary in vitro stimulation of naive CD4(+) T cells, Is conserved through at least 2 rounds of T-helper cell differentiation, and occurs by a cell-intrinsic mechanism that does not depend on overexpression of the Th2-specific factors GATA-3 and c-Maf. Concomitantly, NFAT1(-/-) x IL-4(-/-) mice show increased susceptibility to infection with the intracellular parasite Leishmania major. Moreover, IFN-gamma production in a murine T-cell clone Is sensitive to the selective peptide inhibitor of NFAT, VIVIT. These results suggest that IFN-gamma production by T cells is regulated by NFAT1, most likely at the level of gene transcription. (C) 2001 by The American Society of Hematology.
C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA.
   Dresden Univ Technol, Dept Med 1, Hosp Carl Gustav Carus, D-8027 Dresden, Germany.
   Max Planck Inst Infect Biol, Berlin, Germany.
RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA.
RI Garcia-Cozar, Francisco/A-6212-2013
OI Garcia-Cozar, Francisco/0000-0003-3720-259X
FU NCI NIH HHS [R01 CA-42471]; NIAID NIH HHS [P01 AI-35297]
NR 83
TC 73
Z9 74
U1 0
U2 5
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 SEP 1
PY 2001
VL 98
IS 5
BP 1480
EP 1488
DI 10.1182/blood.V98.5.1480
PG 9
WC Hematology
SC Hematology
GA 467DH
UT WOS:000170685000030
PM 11520798
ER

PT J
AU Barata, JT
   Cardoso, AA
   Nadler, LM
   Boussiotis, VA
AF Barata, JT
   Cardoso, AA
   Nadler, LM
   Boussiotis, VA
TI Interleukin-7 promotes survival and cell cycle progression of T-cell
   acute lymphoblastic leukemia cells by down-regulating the
   cyclin-dependent kinase inhibitor p(27kip1)
SO BLOOD
LA English
DT Article
ID RECEPTOR-DEFICIENT MICE; SEVERE COMBINED IMMUNODEFICIENCY;
   RETINOBLASTOMA PROTEIN; GROWTH-FACTOR; P27(KIP1); BCL-2; TRANSCRIPTION;
   EXPRESSION; APOPTOSIS; ANERGY
AB In normal T-cell development interleukin-7 (IL-7) functions as an antiapoptotic factor by regulating bcl-2 expression in Immature thymocytes and mature T cells. Similar to what occurs in normal immature thymocytes, prevention of spontaneous apoptosis by IL-7 in precursor T-cell acute lymphoblastic leukemia (T-ALL) cells correlates with up-regulation of bcl-2. IL-7 is also implicated in leukemogenesis because IL-7 transgenic mice develop lymphoid malignancies, suggesting that IL-7 may regulate the generation and expansion of malignant cells. This study shows that in the presence of IL-7, T-ALL cells not only up-regulated bcl-2 expression and escaped apoptosis but also progressed In the cell cycle, resulting in sequential induction of cyclin D2 and cyclin A. Down-regulation of p27(kip1) was mandatory for IL-7-mediated cell cycle progression and temporally coincided with activation of cyclin-dependent kinase (cdk)4 and cdk2 and hyperphosphorylation of Rb. Strikingly, forced expression of P27(kip1) in T-ALL cells not only prevented cell cycle progression but also reversed IL-7-mediated up-regulation of bcl-2 and promotion of viability. These results show for the first time that a causative link between IL-7-mediated proliferation and p27(kip1) down-regulation exists in malignant T cells. Moreover, these results suggest that p27(kip1) may function as a tumor suppressor gene not only because it is a negative regulator of cell cycle progression but also because it Is associated with Induction of apoptosis of primary malignant cells. (C) 2001 by The American Society of Hematology.
C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Med Oncol,Dept Med, Boston, MA 02115 USA.
RP Boussiotis, VA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer 547,44 Binney St, Boston, MA 02115 USA.
RI Barata, Joao/D-9181-2015
OI Barata, Joao/0000-0002-4826-8976
FU NCI NIH HHS [CA 68484]; NHLBI NIH HHS [HL 54785]; NIAID NIH HHS [AI
   41584, AI 43552]
NR 52
TC 110
Z9 114
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 SEP 1
PY 2001
VL 98
IS 5
BP 1524
EP 1531
DI 10.1182/blood.V98.5.1524
PG 8
WC Hematology
SC Hematology
GA 467DH
UT WOS:000170685000035
PM 11520803
ER

PT J
AU Elias, AD
   Richardson, P
   Avigan, D
   Ibrahim, J
   Joyce, R
   McDermott, D
   Levine, J
   Warren, D
   McCauley, M
   Wheeler, C
   Frei, E
AF Elias, AD
   Richardson, P
   Avigan, D
   Ibrahim, J
   Joyce, R
   McDermott, D
   Levine, J
   Warren, D
   McCauley, M
   Wheeler, C
   Frei, E
TI A short course of induction chemotherapy followed by two cycles of
   high-dose chemotherapy with stem cell rescue for chemotherapy naive
   metastatic breast cancer: sequential phase I/II studies
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE metastatic breast cancer; hematopoietic stem cell support; double
   transplant
ID SUPPORT; SURVIVAL; TRIAL
AB Two cycles of high-dose chemotherapy with stem cell support (HDC) may increase the total dose delivered and dose intensity. A brief induction phase and different non-cross-resistant agents for each HDC cycle were used to avoid drug resistance. Twenty-six women with metastatic BC had induction and stem cell mobilization with two cycles of doxorubicin/G-CSF given every 14 days. Patients with stable disease or better after induction received HD CTCb followed by HD melphalan and dose-escalated paclitaxel. At 475 mg/m(2) of paclitaxel by 24-h infusion, dose-limiting transient peripheral sensory neuropathy was encountered. No toxic deaths occurred. Complete and near complete response after completion of therapy was achieved in 22 (85%) of 26 patients. The median EFS was 38 months. The median OS has not yet been reached. At a median follow-up of 33 (25-43) months, actuarial EFS and OS were 54% (95% confidence interval (CI), 39-69%) and 69% (95% CI, 56-79%), respectively. This double transplant approach lasts only 14 weeks and is feasible, safe, and tolerable. Whilst selection biases may in part contribute to favorable EFS and OS, a randomized comparison of standard therapy vs double transplant in both metastatic and locally advanced breast cancer is warranted.
C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA.
   Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02115 USA.
RP Elias, AD (reprint author), Univ Colorado, Hlth Sci Ctr, Breast Canc Res Program, 4200 E 9th Ave, Denver, CO 80220 USA.
FU NCI NIH HHS [CA 13849]
NR 25
TC 2
Z9 2
U1 0
U2 1
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 SEP
PY 2001
VL 28
IS 5
BP 447
EP 454
DI 10.1038/sj.bmt.1703148
PG 8
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 473VT
UT WOS:000171069900004
PM 11593317
ER

PT J
AU Sanz, MJ
   Hickey, MJ
   Johnston, B
   McCafferty, DM
   Raharjo, E
   Huang, PL
   Kubes, P
AF Sanz, MJ
   Hickey, MJ
   Johnston, B
   McCafferty, DM
   Raharjo, E
   Huang, PL
   Kubes, P
TI Neuronal nitric oxide synthase (NOS) regulates leukocyte-endothelial
   cell interactions in endothelial NOS deficient mice
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
DE NO; eNOS; nNOS; leukocyte; endothelium; hydrogen peroxide; eNOS mice;
   intravital microscopy
ID ADHESION; RAT; INHIBITION; LACKING; MICROCIRCULATION; SUPEROXIDE;
   OXIDANTS; CORONARY
AB 1 The present study was designed to examine the possible role of neuronal nitric oxide synthase (nNOS) in regulation of leukocyte-endothelial cell interactions in the absence of endothelial nitric oxide synthase (eNOS), using intravital microscopy of the cremasteric microcirculation of eNOS mice.
   2 Baseline leukocyte rolling and adhesion revealed no differences between wild-type and eNOS mice in either the cremasteric or intestinal microcirculations.
   3 Superfusion with L-NAME (100 muM) caused a progressive and significant increase in leukocyte adhesion in both wild-type and eNOS mice, without detecting differences between the two strains of mice.
   4 Superfusion with 7-nitroindazole (100 muM), a selective inhibitor of nNOS, had no effect on leukocyte adhesion in wild-type animals. However, it increased leukocyte adhesion significantly in eNOS (-) mice, which was reversed by systemic L-arginine pre-administration.
   5 Stimulation of the microvasculature with H2O2 (100 muM) induced a transient elevation in leukocyte rolling in wild-type mice. Conversely, the effect persisted during the entire 60 min of experimental protocol in eNOS(-) (-) mice either with or without 7-nitroindazole.
   6 Semi-quantitative analysis by RT-PCR of the mRNA for nNOS levels in eNOS(-) and wildtype animals, showed increased expression of nNOS in both brain and skeletal muscle of eNOS(-) mice.
   7 In conclusion, we have demonstrated that leukocyte-endothelial cell interactions are predominantly modulated by eNOS isoform in postcapillary venules of normal mice, whereas nNOS appears to assume the same role in eNOS(- -) mice. Interestingly, unlike eNOS there was insufficient NO produced by nNOS to overcome leukocyte recruitment elicited by oxidative stress, suggesting that nNOS cannot completely compensate for eNOS.
C1 Univ Calgary, Immunol Res Grp, Calgary, AB T2N 4N1, Canada.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
RP Sanz, MJ (reprint author), Univ Valencia, Fac Med, Dept Farmacol, Av Blasco Ibanez,15-17, Valencia 46010, Spain.
RI Hickey, Michael/A-5429-2012; Johnston, Brent/E-2607-2013
OI Hickey, Michael/0000-0003-2354-357X; 
NR 31
TC 40
Z9 40
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 0007-1188
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD SEP
PY 2001
VL 134
IS 2
BP 305
EP 312
DI 10.1038/sj.bjp.0704234
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 476MQ
UT WOS:000171231200010
PM 11564648
ER

PT J
AU Penson, RT
   Supko, JG
   Seiden, MV
   Fuller, AF
   Berkowitz, RS
   Goodman, A
   Campos, SM
   MacNeill, KM
   Cook, S
   Matulonis, UA
AF Penson, RT
   Supko, JG
   Seiden, MV
   Fuller, AF
   Berkowitz, RS
   Goodman, A
   Campos, SM
   MacNeill, KM
   Cook, S
   Matulonis, UA
TI A Phase I-II study of 96-hour infusional topotecan and paclitaxel for
   patients with recurrent Mullerian tumors
SO CANCER
LA English
DT Article; Proceedings Paper
CT 35th Annual Meeting of the American-Society-of-Clinical-Oncologists
CY MAY 13-18, 1999
CL ATLANTA, GEORGIA
SP Amer Soc Clin Oncol
DE ovarian carcinoma; chemotherapy; clinical trials; pharmacokinetics
ID COLONY-STIMULATING FACTOR; EPITHELIAL OVARIAN-CARCINOMA; 24-HOUR
   CONTINUOUS-INFUSION; GYNECOLOGIC-ONCOLOGY-GROUP; METASTATIC
   BREAST-CANCER; CELL LUNG-CANCER; SALVAGE THERAPY; HUMAN PLASMA; TRIAL;
   TAXOL
AB BACKGROUND. Topotecan and paclitaxel are schedule dependent chemotherapeutic agents with activity against ovarian carcinoma. A Phase I-II study in which both drugs were administered concurrently by 96-hour, continuous, intravenous infusion was performed to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and efficacy of the combination.
   METHODS. Women with ovarian or primary peritoneal carcinoma and documented recurrent disease were eligible for the study. The dose of topotecan was escalated from 1.6 mg/m(2) while maintaining the paclitaxel dose constant at 100 mg/m(2). Plasma concentrations of both drugs were monitored daily during the first cycle of therapy.
   RESULTS. Forty-five patients with a median age of 54 years (range, 42-70 years) received 181 cycles of therapy. Five patients were recruited to each of four dose levels (topotecan 1.6 mg/m(2), 2.0 mg/m(2), 2.8 mg/m(2), and 3.6 mg/m(2)), and an additional 25 patients were treated at the MTD (Phase II). Neutropenia and thrombocytopenia became dose limiting toxicities (DLT) at the fourth dose level. Emesis, mucositis, peripheral neuropathy, diarrhea, and alopecia were mild. Twenty patients (44%) had line-related occlusion, thrombosis, or infection. The mean values (+/- standard deviation) of the apparent steady-state plasma concentrations at the Phase II doses were 2.3 nM +/- 0.5 nM for topotecan lactone, 5.6 nM +/- 2.1 nM for total topotecan, and 40.1 nM +/- 16.8 nM for paclitaxel. There were seven partial responses (Phase II) contributing to an objective response rate of 28% and a median survival time of 11.7 months (range, 0.6-20.1 months).
   CONCLUSIONS. Topotecan at a dose of 2.8 mg/m(2) and paclitaxel at a dose of 100 mg/m(2) administered by concurrent, 96-hour, continuous intravenous infusions shows activity against tumors of Mullerian origin. (C) 2001 American Cancer Society.
C1 Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA.
   Brigham & Womens Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Div Adult Oncol, Dept Med, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA.
RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Cox Bldg 640,100 Blossom St, Boston, MA 02114 USA.
NR 52
TC 7
Z9 8
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI NEW YORK
PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD SEP 1
PY 2001
VL 92
IS 5
BP 1156
EP 1167
DI 10.1002/1097-0142(20010901)92:5<1156::AID-CNCR1434>3.0.CO;2-G
PG 12
WC Oncology
SC Oncology
GA 472FC
UT WOS:000170972000014
PM 11571729
ER

PT J
AU Vargas, SO
   French, CA
   Faul, PN
   Fletcher, JA
   Davis, IJ
   Dal Cin, P
   Perez-Atayde, AR
AF Vargas, SO
   French, CA
   Faul, PN
   Fletcher, JA
   Davis, IJ
   Dal Cin, P
   Perez-Atayde, AR
TI Upper respiratory tract carcinoma with chromosomal translocation 15;19 -
   Evidence for a distinct disease entity of young patients with a rapidly
   fatal course
SO CANCER
LA English
DT Article
DE carcinoma; thymic carcinoma; cytogenetics; chromosome 15; chromosome 19;
   laryngeal carcinoma; nasopharyngeal carcinoma; lymphoepithelioma;
   salivary gland carcinoma; translocation
ID COMPARATIVE GENOMIC HYBRIDIZATION; LYMPHOEPITHELIOMA-LIKE CARCINOMAS;
   COPY NUMBER LOSSES; UNDIFFERENTIATED CARCINOMA; NASOPHARYNGEAL
   CARCINOMA; LARYNGEAL CARCINOMA; THYROID-CARCINOMA; CELL CARCINOMA;
   TUMORS; LARYNGOHYPOPHARYNX
AB BACKGROUND. Carcinoma of the upper respiratory tract is rare in childhood, and cytogenetic aberrations have not been characterized in this population. The chromosomal translocation 15;19 has been reported four times previously. All patients were young and had tumors arising in the thorax. The three reports that provide clinical follow-up all describe superior vena cava syndrome and death soon after presentation. Ali tumors were diagnosed as carcinoma (three undifferentiated, one mucoepidermoid), and the authors suggested thymus, lung, or germ cell origin.
   METHODS. The authors investigated the clinical and pathologic findings in two patients with poorly differentiated carcinoma showing evidence of t(15;19). This included a 13-year-old girl with a rapidly growing epiglottic mass, leading to superior vena cava syndrome and death and a 12-year-old girl with an aggressive nasopharyngeal. mass showing intracranial extension.
   RESULTS. The laryngeal tumor was poorly differentiated, with vesicular nuclei, prominent nucleoli, extensive necrosis, and a lymphoplasmacytic infiltrate; cells were positive for cytokeratin and negative for lymphoma, melanoma, germ cell, and endocrine markers. Electron microscopy showed rare intermediate junctions and basal lamina. The nasopharyngeal tumor was poorly differentiated with areas of obvious squamous differentiation observed histologically, immunophenotypically, and ultrastructurally. Cytogenetic and fluorescent in situ hybridization studies were consistent with t(15;19)(q13;p13.1) in both cases. Both children received chemo- and radiotherapy. The first child died of disease after 36 weeks; autopsy revealed tumor in the larynx with spread to the skin/subcutis (neck and thorax) and lymph nodes (cervical, subcarinal, and pulmonary hilar). The second child developed widespread bony metastes and died of disease after 13 weeks.
   CONCLUSIONS. in conjunction with previous reports, the authors' findings show that t(15;19) is part of a distinct clinicopathologic entity characterized by young age, midline carcinoma of the neck or upper thorax, and a rapidly fatal course. Female gender and superior vena cava syndrome are common. The histogenesis of these distinctive tumors is unknown. The authors' findings suggest origin in the upper airway, perhaps from submucosal glands. (C) 2001 American Cancer Society.
C1 Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   Childrens Hosp, Dept Med, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Vargas, SO (reprint author), Childrens Hosp, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA.
NR 50
TC 50
Z9 52
U1 0
U2 1
PU JOHN WILEY & SONS INC
PI NEW YORK
PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD SEP 1
PY 2001
VL 92
IS 5
BP 1195
EP 1203
DI 10.1002/1097-0142(20010901)92:5<1195::AID-CNCR1438>3.0.CO;2-3
PG 9
WC Oncology
SC Oncology
GA 472FC
UT WOS:000170972000018
PM 11571733
ER

PT J
AU Billingsley, KG
   Maynard, C
   Schwartz, DL
   Dominitz, JA
AF Billingsley, KG
   Maynard, C
   Schwartz, DL
   Dominitz, JA
TI The use of trimodality therapy for the treatment of operable esophageal
   carcinoma in the veteran population - Patient survival and outcome
   analysis
SO CANCER
LA English
DT Article
DE esophageal neoplasms; surgery; radiation therapy; chemotherapy
ID SQUAMOUS-CELL CARCINOMA; PREOPERATIVE RADIOTHERAPY; CANCER STATISTICS;
   RADIATION-THERAPY; SURGERY; CHEMOTHERAPY; TRIAL; MULTICENTER; INDEX
AB BACKGROUND. in an effort to improve the cure rates associated with surgical therapy, neoadjuvant chemoradiotherapy is being used with increasing frequency before resection (trimodality therapy). A variety of clinical trials have reviewed this approach, but only one study to the authors' knowledge has shown a survival benefit for trimodality therapy. The extent to which trimodality therapy has gained acceptance in general practice is not clear. The objective of the current study was to determine the extent to which both surgery and trimodality therapy are used for the management of esophageal carcinoma within a large, national health care system and to determine the outcome of patients treated with these treatment approaches.
   METHODS. The current study was a retrospective cohort study. The study population was comprised of all veterans who underwent either surgery alone or trimodality therapy for operable esophageal carcinoma between the fiscal years of 1993 and 1997. Data were obtained from the Veterans Administration Patient Treatment File, Outpatient Clinic File, and the Beneficiary Identification Record Locator System. The main outcome measures were perioperative mortality and patient survival.
   RESULTS. During the study period, 695 patients underwent either surgery alone or trimodality therapy for esophageal carcinoma. Five hundred thirty-four (77%) patients were treated with surgery only. One hundred sixty-one (23%) patients underwent surgery after induction ch emo radiotherapy (trimodality therapy). Patients selected for trimodality therapy were younger (mean age, 60.8 years vs. 65.6 years), had fewer comorbidities, and were more likely to have a midesophageal tumor. The median survival for all patients was 15.2 months. The type of treatment had no apparent effect on survival. Favorable prognostic factors included younger age, a distal esophageal tumor, and the absence of metastases. The overall perioperative mortality was 13.7%. The use of trimodality therapy did not increase perioperative mortality.
   CONCLUSIONS. Trimodality therapy is commonly used within the VA system. The nonrandomized nature of this study does not allow comparison of trimodality therapy to surgery alone, but the overall survival was limited for all patients. The predictors of survival are related to the biology of the disease, and they include patient age, tumor location, and stage at diagnosis. Published 2001 by the American Cancer Society.
C1 Univ Washington, Sch Med, Dept Surg, Seattle, WA 98108 USA.
   Vet Affairs Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA 98108 USA.
   Univ Washington, Sch Med, Dept Hlth Serv Res, Seattle, WA 98108 USA.
   Vet Affairs Puget Sound Hlth Care Syst, Dept Hlth Serv Res, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
   Univ Washington, Sch Med, Dept Radiat Oncol, Seattle, WA 98108 USA.
   Vet Affairs Puget Sound Hlth Care Syst, Dept Radiat Oncol, Seattle, WA USA.
   Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA.
   Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Dept Med, Div Gastroenterol, Seattle, WA USA.
RP Billingsley, KG (reprint author), Univ Washington, Sch Med, Dept Surg, 112,1660 S Columbian Way, Seattle, WA 98108 USA.
RI Maynard, Charles/N-3906-2015
OI Maynard, Charles/0000-0002-1644-7814
NR 22
TC 7
Z9 7
U1 2
U2 2
PU JOHN WILEY & SONS INC
PI NEW YORK
PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0008-543X
J9 CANCER
JI Cancer
PD SEP 1
PY 2001
VL 92
IS 5
BP 1272
EP 1280
DI 10.1002/1097-0142(20010901)92:5<1272::AID-CNCR1448>3.0.CO;2-A
PG 9
WC Oncology
SC Oncology
GA 472FC
UT WOS:000170972000028
PM 11571743
ER

PT J
AU Supko, JG
   Garcia-Carbonero, R
   Puchalski, TA
   Malspeis, L
AF Supko, JG
   Garcia-Carbonero, R
   Puchalski, TA
   Malspeis, L
TI Plasma pharmacokinetics and bioavailability of
   1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea after intravenous and
   oral administration to mice and dogs
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE antineoplastic agents; nitrosoureas; pharmacokinetics; preclinical
   studies
ID AMINO-ACID AMIDES; GLIOMA CELL-LINE; TRANSPORT; SK-MG-1; BCNU;
   CHLOROETHYLNITROSOUREA; SARCOSINAMIDE; CONGENERS; SYSTEM; ASSAY
AB Purpose: Chloroethylnitrosoureas are among the most widely used chemotherapeutic agents for the treatment of brain tumors. SarCNU (1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea) is an investigational nitrosourea analogue that has shown greater antitumor activity and a more favorable toxicity profile than 1,3-bis(2-chloroethyl)-1-nitrosourea in preclinical studies. The purpose of the present study was to characterize the plasma pharmacokinetics and oral bioavailability of SarCNU in mice and dogs treated by intravenous infusion and gastric intubation. Methods: SarCNU was administered to mice by i.v. injection or orally at doses ranging from 10 to 100 mg/kg. Plasma samples were obtained from groups of five animals at each time-point at intervals ranging from 3 min to 2.5 h after dosing. A group of three male beagle dogs were treated with Sar CNU 10 mg/kg given both by i.v. infusion and orally in a crossover design. The concentration of SarCNU in plasma was measured by high-performance liquid chromatography. Results: During the initial 90 min after i.v. injection to mice, SarCNU was eliminated from plasma in a monoexponential manner with a mean half-life of 9.8 +/- 0.8 min. The total plasma clearance was 47.3 +/- 8.7 ml/min per kg and the apparent volume of distribution was 0.7 +/- 0.11/kg. SarCNU exhibited linear pharmacokinetic behavior following both i.v. and oral administration of doses ranging from approximately 10 to 100 mg/kg. Peak plasma levels provided by it dose of 100 mg/kg given by the i.v. and oral routes were 142.4 mug/ml (0.5 min) and 27.8 mug/ml (9.8 min), respectively. The mean oral bioavailability of the drug was 57.3 +/- 12.6% in mice. In comparison, the disposition of SarCNU in dogs after rapid i.v. injection was biexponential, with half-lives of 5.4 +/- 8.4 min and 40.8 +/- 9.0 min for the initial and terminal disposition phases. respectively. Mean values of the total plasma clearance and apparent volume of distribution were 17.8 +/- 1.8 ml/min per kg and 1.1 +/- 0.3 l/kg, respectively. The C-max was 18.5 +/- 6.5 mug/ml after i.v. injection and 8.5 +/- 0.4 mug/ml after oral administration of it 10 mg/kg dose. Oral bioavailability or the drug in dogs (71.7 +/- 21.2%) was greater than that observed in mice. Conclusions: SarCNU exhibited linear and consistent pharmacokinetics in mice and dogs with very good oral bioavailability in both species. These findings support the rationale for evaluating SarCNU given by the oral route of administration in phase I clinical trials.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02114 USA.
   NCI, Lab Pharmaceut Chem, Dev Therapeut Program, Div Canc Treatment,NIH, Bethesda, MD 20892 USA.
RP Supko, JG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, 55 Fruit St, Boston, MA 02114 USA.
NR 26
TC 2
Z9 2
U1 0
U2 0
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0344-5704
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD SEP
PY 2001
VL 48
IS 3
BP 202
EP 208
DI 10.1007/s002800100326
PG 7
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 476XZ
UT WOS:000171255200004
PM 11592341
ER

PT J
AU Martuza, RL
AF Martuza, RL
TI Development of herpes vectors for cancer therapy
SO CANCER GENE THERAPY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 0929-1903
J9 CANCER GENE THER
JI Cancer Gene Ther.
PD SEP
PY 2001
VL 8
IS 9
MA 21
BP 690
EP 690
PG 1
WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
   Medicine, Research & Experimental
SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity;
   Research & Experimental Medicine
GA 475QM
UT WOS:000171175600029
ER

PT J
AU D'Amico, AV
AF D'Amico, AV
TI Perineural invasion as a predictor of PSA outcome following local
   therapy for patients with clinically localized prostate cancer
SO CANCER JOURNAL
LA English
DT Editorial Material
ID RADICAL PROSTATECTOMY; PATHOLOGICAL STAGE; NEEDLE-BIOPSY; ADENOCARCINOMA
C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA.
NR 8
TC 9
Z9 9
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 SEP-OCT
PY 2001
VL 7
IS 5
BP 375
EP 376
PG 2
WC Oncology
SC Oncology
GA 485BZ
UT WOS:000171734800004
PM 11693895
ER

PT J
AU Rao, PS
   Palacios, IF
   Bach, RG
   Bitar, SR
   Sideris, EB
AF Rao, PS
   Palacios, IF
   Bach, RG
   Bitar, SR
   Sideris, EB
TI Platypnea-orthodeoxia: Management by transcatheter buttoned device
   implantation
SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
LA English
DT Article; Proceedings Paper
CT 49th Annual Scientific Session of the American-College-of-Cardiology
CY MAR 12-15, 2000
CL ANAHEIM, CALIFORNIA
SP Amer Coll Cardiol
DE atrial septal defect; buttoned device; interatrial right-to-left shunt;
   nonsurgical closure; patent foramen ovale; platypnea-orthodeoxia;
   transcatheter occlusion
ID ATRIAL SEPTAL-DEFECT; PATENT FORAMEN OVALE; LEFT INTERATRIAL SHUNT;
   STRETCHED DIAMETER; OCCLUSION; CLOSURE; PNEUMONECTOMY; PRESSURES;
   AMIODARONE; EXPERIENCE
AB Dyspnea and arterial desaturation on upright position in elderly subjects is described as platypnea-orthodeoxia syndrome (POS) and in some patients it is due to right-to-left shunt across the atrial septal defect (ASD)/patent foramen ovale (PFO). Surgical closure of ASD/PFO has been the only available treatment option. Buttoned device has been used for occlusion of ostium secundum ASD, PFO associated with presumed paradoxical embolism and cerebrovascular accidents and ASD/PFO in association with other congenital heart defects causing right-to-left shunt. The objective of this article is to describe the use of buttoned device in effectively occluding ASD/PFO to relieve hypoxemia of POS. During a 4-year period ending January 2000, 10 patients, ages 71 +/- 9 (range 60-83) years with POS underwent buttoned device closure of their ASD/PFO. Echocardiographic and balloon-stretched atrial defect sizes were 8 +/- 3 mm and 12 +/- 3 mm, respectively. The ASD/PFO were occluded with devices ranging in size from 25 to 40 mm delivered via 9 French, long, blue Cook sheaths; eight had an additional 25- or 35-mm occluder placed on the right atrial side. The oxygen saturation increased (P < 0.001) from 76 +/- 7% (range 69-86%) to 95 +/- 2% (range 92-98%). No complications were encountered. Relief of symptoms was seen in all patients. Follow-up of 1-36 months (median 12 months) revealed persistent improvement of symptoms. Buttoned device occlusion of ASD/PFO to relieve hypoxemia of POS is feasible, safe, and effective and is an excellent alternative to surgery. (C) 2001 Wiley-Liss, Inc.
C1 St Louis Univ, Sch Med, St Louis, MO 63104 USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA.
   Athenian Inst Pediat Cardiol, Athens, Greece.
RP Rao, PS (reprint author), St Louis Univ, Sch Med, 1462 S Grand Blvd, St Louis, MO 63104 USA.
NR 49
TC 23
Z9 23
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 1522-1946
J9 CATHETER CARDIO INTE
JI Catheter. Cardiovasc. Interv.
PD SEP
PY 2001
VL 54
IS 1
BP 77
EP 82
DI 10.1002/ccd.1243
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 474KH
UT WOS:000171105300016
PM 11553954
ER

PT J
AU Yang, HF
   Kaelin, WG
AF Yang, HF
   Kaelin, WG
TI Molecular pathogenesis of the von Hippel-Lindau hereditary cancer
   syndrome: Implications for oxygen sensing
SO CELL GROWTH & DIFFERENTIATION
LA English
DT Review
ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA;
   CENTRAL-NERVOUS-SYSTEM; SPORADIC CEREBELLAR HEMANGIOBLASTOMAS;
   BIOLOGICALLY-ACTIVE PRODUCT; POLYCYSTIC KIDNEY-DISEASE;
   HYPOXIA-INDUCIBLE FACTORS; UBIQUITIN LIGASE COMPLEX; FACTOR-ALPHA
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
   Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St,Mayer Bldg Room 457, Boston, MA 02115 USA.
NR 131
TC 28
Z9 30
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 1044-9523
J9 CELL GROWTH DIFFER
JI Cell Growth Differ.
PD SEP
PY 2001
VL 12
IS 9
BP 447
EP 455
PG 9
WC Cell Biology
SC Cell Biology
GA 476HL
UT WOS:000171220100001
PM 11571227
ER

PT J
AU Majumder, PK
   Mishra, NC
   Sun, XG
   Bharti, A
   Kharbanda, S
   Saxena, S
   Kufe, D
AF Majumder, PK
   Mishra, NC
   Sun, XG
   Bharti, A
   Kharbanda, S
   Saxena, S
   Kufe, D
TI Targeting of protein kinase C delta to mitochondria in the oxidative
   stress response
SO CELL GROWTH & DIFFERENTIATION
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOCHROME-C; ACTIVATION; APOPTOSIS;
   CELLS; TRANSLOCATION; REQUIREMENT; NUCLEAR; DNA
AB The cellular response to oxidative stress includes the release of mitochondrial cytochrome c and the induction of apoptosis. Here we show that treatment of diverse cells with hydrogen peroxide (H2O2) induces the targeting of protein kinase C delta (PKC delta) to mitochondria. The results demonstrate that H2O2-induced activation of PKC delta is necessary for translocation of PKC delta from the cytoplasm to the mitochondria. The results also show that mitochondrial targeting of PKC delta Is associated with the loss of mitochondrial transmembrane potential and release of cytochrome c. The functional importance of this event is also supported by the demonstration that H2O2-induced apoptosis is blocked by the inhibition of PKC delta activation and translocation to mitochondria. These findings indicate that mitochondrial targeting of PKC delta is required, at least in part, for the apoptotic response of cells to oxidative stress.
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 24
TC 133
Z9 136
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 1044-9523
J9 CELL GROWTH DIFFER
JI Cell Growth Differ.
PD SEP
PY 2001
VL 12
IS 9
BP 465
EP 470
PG 6
WC Cell Biology
SC Cell Biology
GA 476HL
UT WOS:000171220100003
PM 11571229
ER

PT J
AU Hayes, DF
   Yamauchi, H
   Broadwater, G
   Cirrincione, CT
   Rodrigue, SP
   Berry, DA
   Younger, J
   Panasci, LL
   Millard, F
   Duggan, DB
   Norton, L
   Henderson, IC
AF Hayes, DF
   Yamauchi, H
   Broadwater, G
   Cirrincione, CT
   Rodrigue, SP
   Berry, DA
   Younger, J
   Panasci, LL
   Millard, F
   Duggan, DB
   Norton, L
   Henderson, IC
TI Circulating HER-2/erbB-2/c-neu (HER-2) extracellular domain as a
   prognostic factor in patients with metastatic breast cancer: Cancer and
   leukemia group B study 8662
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID C-ERBB-2 ANTIGEN LEVELS; ADJUVANT THERAPY; TUMOR-MARKERS; PHASE-II;
   COMBINATION CHEMOTHERAPY; TAMOXIFEN RESISTANCE; ENDOCRINE THERAPY;
   PREDICTIVE-VALUE; NEU-ONCOGENE; EXPRESSION
AB Purpose: The HER-2/erbB-2/c-neu (HER-2) proto-oncogene is a M(r) 185,000 transmembrane tyrosine kinase that is amplified and/or overexpressed by 20-40% of breast cancers. HER-2 has been associated with worse prognosis and resistance or sensitivity to specific treatment. We evaluated circulating levels of extracellular domain of HER-2 (ECD/HER-2) in metastatic breast cancer patients and investigated the prognostic and predictive significance of circulating HER-2 levels regarding endocrine therapy or chemotherapy.
   Experimental Design: Plasma samples from 242 patients were assayed for circulating ECD/HER-2 levels, using a sandwich enzyme immunoassay. ECD/HER-2 was correlated with clinical data gathered from these patients while they were participating in prospective Cancer and Leukemia Group B (CALGB) therapeutic protocols for metastatic breast cancer.
   Results: Eighty-nine (37%) of 242 patients had elevated ECD/HER-2 levels (greater than or equal to 10.5 ng/ml). ECD/HER-2 was significantly associated with tumor burden, progesterone receptor levels, and presence of visceral metastases. Patients with elevated pretreatment levels had a significantly shorter OS but not time-to-progression than did those with ECD/HER-2 levels < 10.5ng/ml in univariate analysis. In univariate but not multivariate subset analyses, among patients treated with endocrine therapy (megestrol acetate), elevated initial ECD/HER-2 was associated with worse OS compared with nonelevated patients. However, among patients treated with chemotherapy (mainly anthracycline-containing regimens), OS did not differ significantly. Rates of response to either endocrine therapy or chemotherapy were similar for patients with elevated and nonelevated ECD/HER-2 levels.
   Conclusions: ECD/HER-2 levels are elevated in 35-40% of patients with metastatic breast cancer. Elevated ECD/HER-2 levels are associated with a poorer prognosis in these patients. However, no predictive role for ECD/HER-2 was identified, either for endocrine therapy or for anthracycline-based chemotherapy in the metastatic setting.
C1 Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA.
   CALGB Stat Ctr, Durham, NC 27710 USA.
   Down E Orthoped Assoc, Bangor, ME 04401 USA.
   Univ Texas, MD Anderson Canc Ctr, Houston, TX 77080 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   McGill Dept Oncol, Montreal, PQ, Canada.
   Naval Hosp, San Diego, CA 92134 USA.
   SUNY, Upstate Med Ctr, Syracuse, NY 13210 USA.
   Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
   Univ Calif San Francisco, San Francisco, CA 94114 USA.
RP Hayes, DF (reprint author), 6312 CCGC,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA.
FU NCI NIH HHS [CA47642, CA02599, CA03927, CA04326, CA04457, CA07968,
   CA08025, CA11028, CA11789, CA12046, CA12449, CA16450, CA21060, CA26806,
   CA31809, CA31946, CA31983, CA32291, CA33601, CA35406, CA37135, CA37447,
   CA41287, CA45374, CA45389, CA45400, CA45418, CA45564, CA45808, CA47545,
   CA47555, CA47559, CA47577, CA54697, CA74811, CA77298, CA77406, CA77440,
   CA77597, CA77651, R03CA53336]; PHS HHS [60138]
NR 56
TC 76
Z9 84
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP
PY 2001
VL 7
IS 9
BP 2703
EP 2711
PG 9
WC Oncology
SC Oncology
GA 473GD
UT WOS:000171031400015
PM 11555582
ER

PT J
AU Shintani, S
   Mihara, M
   Terakado, N
   Nakahara, Y
   Matsumura, T
   Kohno, Y
   Ohyama, H
   McBride, J
   Kent, R
   Todd, R
   Tsuji, T
   Wong, DTW
AF Shintani, S
   Mihara, M
   Terakado, N
   Nakahara, Y
   Matsumura, T
   Kohno, Y
   Ohyama, H
   McBride, J
   Kent, R
   Todd, R
   Tsuji, T
   Wong, DTW
TI Reduction of p12(DOC-1) expression is a negative prognostic indicator in
   patients with surgically resected oral squamous cell carcinoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; CYCLIN D1 EXPRESSION; NECK-CANCER;
   MOLECULAR-BIOLOGY; NUCLEAR ANTIGEN; HEAD; PROTEIN; P53; CLASSIFICATION;
   PROLIFERATION
AB Purpose: p12(DOC-1) is a growth suppressor that negatively regulates cyclin-dependent kinase 2 (CDK2) activities. Expression of p12(DOC-1) is reduced and/or lost in tumor tissues. The purpose of this study is to correlate in vivo the expression of p12(DOC-1) in oral cancer tissues by immunohistochemistry with clinical and pathological parameters.
   Experimental Design: Twenty-five cases of normal oral mucosa and 127 cases of oral squamous cell carcinomas were evaluated. Patients' charts were reviewed for clinical, pathological, and 10-year survival data. Because p12(DOC-1) is a growth suppressor and associates with CDK2, parallel immunostaining was done for proliferating cell nuclear antigen and CDK2 to evaluate cell proliferation and potential correlation with CDK2.
   Results: Our results showed that strong p12(DOC-1) staining was uniformly seen in normal oral mucosa. p12(DOC-1) staining was reduced or absent in 81 cases (63.8%) of oral squamous cell carcinomas. Decreased p12(DOC-1) staining (< 25% of cells stained) correlated with tumor mode of invasion (P = 0.001) and higher proliferating cell nuclear antigen (P = 0.0028) and CDK2 (P = 0.0020) expression. Survival analysis showed significant correlation of low p12(DOC-1) expression with the risk of cervical lymph node metastasis (P = 0.001) and patients' 10-year survival status (P = 0.0214).
   Conclusions: These results allow us to conclude that reduction of P12(DOC-1) protein expression is a frequent event in oral cancers. Intratumor immunohistochemical evaluation of p12(DOC-1) expression can be an adjunctive prognostic indicator for patients with oral cancer.
C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Pathol,Lab Mol Pathol, Boston, MA 02115 USA.
   Forsyth Inst, Boston, MA 02115 USA.
   Okayama Univ, Sch Dent, Dept Oral & Maxillofacial Surg 2, Okayama 700, Japan.
RP Wong, DTW (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Pathol,Lab Mol Pathol, 188 Longwood Ave, Boston, MA 02115 USA.
FU NIDCR NIH HHS [R29 DE11983, P01 DE 12467]
NR 26
TC 41
Z9 46
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP
PY 2001
VL 7
IS 9
BP 2776
EP 2782
PG 7
WC Oncology
SC Oncology
GA 473GD
UT WOS:000171031400025
PM 11555592
ER

PT J
AU Kataoka, A
   Sadanaga, N
   Mimori, K
   Ueo, H
   Barnard, GF
   Sugimachi, K
   Auclair, D
   Chen, LB
   Mori, M
AF Kataoka, A
   Sadanaga, N
   Mimori, K
   Ueo, H
   Barnard, GF
   Sugimachi, K
   Auclair, D
   Chen, LB
   Mori, M
TI Overexpression of HRad17 mRNA in human breast cancer: Correlation with
   lymph node metastasis
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CHECKPOINT CONTROL GENE; HUMAN HOMOLOG; CARCINOMA; ACCUMULATION;
   PROTEIN; MARKER; 4Q
AB Purpose: A novel human gene, designated HRad17, was identified as the human homologue of the Rad17 of Schizosaccharomyces pombe and Rad24 of Saccharomyces cerevisiae. In yeast, these genes play a critical role in maintaining genomic stability. The aim of this study was to evaluate the expression of HRad17 in human breast cancer.
   Experimental Design: We investigated HRad17 mRNA expression in 64 cases of human breast cancer by means of reverse-transcription-PCR in situ hybridization, and immunohistochemistry.
   Results: The HRad17 mRNA was overexpressed in 35 cases (54.7%). Twenty-four (68.6%) of 35 cases with HRad17 overexpression in cancer tissues were node-positive, whereas only 8 (27.6%) of 29 cases without HRad17 overexpressions were node-positive. The expression of HRad17 mRNA correlated with both lymph node metastasis (P = 0.001) and high Ki67 labeling index (P = 0.006). Although not significantly different, expression of HRad17 mRNA tended to correlate with tumor size (P = 0.06) and expression of mutant p53 protein (P = 0.10). Furthermore, expression of HRad17 mRNA was an independent predictor of axillary lymph node metastasis as well as of lymphatic permeation by multivariate analysis (P < 0.0001).
   Conclusions: Our study demonstrates that HRad17 might be related to the development of lymph node metas, tasis in human breast cancers. Although its function still remains unclear, the expression of HRad17 mRNA could open up a new window for the diagnostic staging and treatment of human breast cancers.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   Kyushu Univ, Med Inst Bioregulat, Dept Surg, Beppu, Oita 8740838, Japan.
   Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Inst, Philadelphia, PA 19107 USA.
   Oita Prefectural Hosp, Dept Surg, Oita 8708511, Japan.
   Univ Massachusetts, Med Ctr, Div Digest Dis & Nutr, Worcester, MA 01655 USA.
   Kyushu Univ, Fac Med, Dept Surg 2, Fukuoka 8128582, Japan.
RP Mori, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
RI U-ID, Kyushu/C-5291-2016
NR 27
TC 7
Z9 13
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI BIRMINGHAM
PA PO BOX 11806, BIRMINGHAM, AL 35202 USA
SN 1078-0432
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD SEP
PY 2001
VL 7
IS 9
BP 2815
EP 2820
PG 6
WC Oncology
SC Oncology
GA 473GD
UT WOS:000171031400031
PM 11555598
ER

PT J
AU Pappas, PG
   Perfect, JR
   Cloud, GA
   Larsen, RA
   Pankey, GA
   Lancaster, DJ
   Henderson, H
   Kauffman, CA
   Haas, DW
   Saccente, M
   Hamill, RJ
   Holloway, MS
   Warren, RM
   Dismukes, WE
AF Pappas, PG
   Perfect, JR
   Cloud, GA
   Larsen, RA
   Pankey, GA
   Lancaster, DJ
   Henderson, H
   Kauffman, CA
   Haas, DW
   Saccente, M
   Hamill, RJ
   Holloway, MS
   Warren, RM
   Dismukes, WE
TI Cryptococcosis in human immunodeficiency virus-negative patients in the
   era of effective azole therapy
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 4th International Conference on Cryptococcus and Cryptococcosis
CY SEP 12-17, 1999
CL LONDON, ENGLAND
ID CELL-MEDIATED-IMMUNITY; PULMONARY CRYPTOCOCCOSIS; AMPHOTERICIN-B;
   MENINGITIS; FLUCONAZOLE; NEOFORMANS; AIDS; FLUCYTOSINE; INFECTION
AB We conducted a case study of human immunodeficiency virus (HIV)-negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age greater than or equal to 60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality.
C1 Univ Alabama, Birmingham Med Ctr, Birmingham, AL 35294 USA.
   Duke Univ, Med Ctr, Durham, NC USA.
   Univ So Calif, Med Ctr, Los Angeles, CA USA.
   Oschner Clin, New Orleans, LA USA.
   Methodist Hosp, Memphis, TN USA.
   Vanderbilt Univ, Med Ctr, Nashville, TN USA.
   Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
   Univ Michigan, Ann Arbor, MI 48109 USA.
   Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA.
   Univ Arkansas, Med Ctr, Little Rock, AR 72204 USA.
   Baylor Coll Med, Houston, TX 77030 USA.
   Houston Vet Affairs Med Ctr, Houston, TX USA.
RP Pappas, PG (reprint author), Univ Alabama, Birmingham Med Ctr, 1900 Univ Blvd,229 Tinsley Harrison Tower, Birmingham, AL 35294 USA.
FU PHS HHS [N01-A1-65296]
NR 32
TC 263
Z9 281
U1 0
U2 8
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP
PY 2001
VL 33
IS 5
BP 690
EP 699
DI 10.1086/322597
PG 10
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 459VB
UT WOS:000170271200014
PM 11477526
ER

PT J
AU Hadigan, C
   Jeste, S
   Anderson, EJ
   Tsay, R
   Cyr, H
   Grinspoon, S
AF Hadigan, C
   Jeste, S
   Anderson, EJ
   Tsay, R
   Cyr, H
   Grinspoon, S
TI Modifiable dietary habits and their relation to metabolic abnormalities
   in men and women with human immunodeficiency virus infection and fat
   redistribution
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
ID ANTIRETROVIRAL THERAPY HAART; INSULIN-RESISTANCE; DIABETES-MELLITUS;
   GLUCOSE-TOLERANCE; LIPODYSTROPHY
AB We assessed the relationship between dietary intake, body composition, and metabolic parameters in 85 consecutive human immunodeficiency virus (HIV)-infected patients with fat redistribution. Dietary history and values for fasting glucose, insulin, lipids, and oral glucose tolerance were obtained for 62 men and 23 women with HIV infection and fat redistribution (mean age standard error of the mean [SEM], 43.5 +/- 0.9 years; mean body mass index [BMI] +/- SEM, 26.3 +/- 0.5 kg/m(2)). A multivariate regression analysis was used to predict insulin area under the curve (AUC) following the oral glucose tolerance test; this included age, sex, BMI, waist-to-hip ratio, kilocalories, duration of protease inhibitor (PI) use, fat redistribution pattern, alcohol intake, dietary fiber intake, and polyunsaturated-to-saturated (P: S) fat ratio. Only age (P=.004), PI use duration (P=.02), and P: S fat ratio (P=.003) were positively associated with insulin AUC. Dietary fiber intake was inversely associated with the insulin AUC (P=.001). In a similar analysis, alcohol consumption was a significant positive predictor of low-density lipoprotein cholesterol. Polyunsaturated fats, fiber, and alcohol are strongly associated with insulin resistance and hyperlipidemia in this population and may be important targets for dietary modification.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Neuroendocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Clin Res Ctr, Boston, MA 02114 USA.
   MIT, Clin Res Ctr, Boston, MA USA.
RP Hadigan, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Neuroendocrine Unit, 55 Fruit St,BUL457-B, Boston, MA 02114 USA.
FU NCRR NIH HHS [M01-RR01066, M01-RR300088]; NIDDK NIH HHS [K23-DK02844,
   R01-DK59535, T32-DK07703]
NR 23
TC 45
Z9 45
U1 0
U2 1
PU UNIV CHICAGO PRESS
PI CHICAGO
PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA
SN 1058-4838
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD SEP
PY 2001
VL 33
IS 5
BP 710
EP 717
DI 10.1086/322680
PG 8
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 459VB
UT WOS:000170271200017
PM 11486294
ER

PT J
AU Batchelor, T
   Leahy, N
   Kaufman, D
AF Batchelor, T
   Leahy, N
   Kaufman, D
TI High-dose methotrexate for isolated central nervous system relapse in
   patients with testicular non-Hodgkin's lymphoma
SO CLINICAL LYMPHOMA
LA English
DT Article
DE high-dose methotrexate; CNS relapse; testicular non-Hodgkin's lymphoma
ID INTRATHECAL CHEMOTHERAPY; INTRAVENOUS-INFUSION; INVOLVEMENT; RECURRENCE
AB Four consecutive patients with testicular non-Hodgkin's lymphoma who initially achieved a complete response to treatment with standard combination therapy later developed isolated central nervous system (CNS) relapses. At the time of CNS relapse, staging evaluations were negative for lymphoma outside the nervous system in all 4 patients. These patients were treated with high-dose intravenous methotrexate alone, and a complete remission was achieved in all 4 patients.
C1 Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA.
RP Batchelor, T (reprint author), Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, 100 Blossom St, Boston, MA 02114 USA.
NR 18
TC 18
Z9 20
U1 0
U2 0
PU CANCER INFORMATION GROUP, LP
PI DALLAS
PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA
SN 1526-9655
J9 CLIN LYMPHOMA
JI Clin. Lymphoma
PD SEP
PY 2001
VL 2
IS 2
BP 116
EP 119
DI 10.3816/CLM.2001.n.017
PG 4
WC Oncology
SC Oncology
GA 480RX
UT WOS:000171477200008
PM 11707852
ER

PT J
AU Manning, K
   Jacobson, AF
AF Manning, K
   Jacobson, AF
TI Dehydration-induced renal dysfunction identified on a bone scan
SO CLINICAL NUCLEAR MEDICINE
LA English
DT Article
DE acute tubular necrosis; bone scan; renal activity
C1 VA Puget Sound Hlth Care Syst, Med Sect, Seattle, WA 98108 USA.
   Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA.
RP Jacobson, AF (reprint author), VA Puget Sound Hlth Care Syst, Med Sect, S-113-NUC,1660 S Columbian Way, Seattle, WA 98108 USA.
NR 4
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0363-9762
J9 CLIN NUCL MED
JI Clin. Nucl. Med.
PD SEP
PY 2001
VL 26
IS 9
BP 802
EP 802
DI 10.1097/00003072-200109000-00023
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 482YK
UT WOS:000171604700023
PM 11507312
ER

PT J
AU Warner, JJP
AF Warner, JJP
TI Dedication to Dr. Richard Caspari
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Biographical-Item
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Warner, JJP (reprint author), Massachusetts Gen Hosp, 275 Cambridge St,4th Floor, Boston, MA 02114 USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
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 SEP
PY 2001
IS 390
BP 3
EP 4
PG 2
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 468VJ
UT WOS:000170778600002
ER

PT J
AU Mayfield, JB
   Carter, C
   Wang, C
   Warner, JJP
AF Mayfield, JB
   Carter, C
   Wang, C
   Warner, JJP
TI Arthroscopic shoulder reconstruction - Fast-track recovery and
   outpatient treatment
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Article
ID BRACHIAL-PLEXUS BLOCK; AMBULATORY SURGERY; PULMONARY-FUNCTION;
   ANESTHESIA; PACU
AB Arthroscopic shoulder reconstructive surgery has been handled in many different ways. However, there currently is significant evidence and experience to show that doing this surgery on an outpatient basis is not only cost-effective and efficient, but safe and beneficial to patients. New arthroscopic surgical techniques and the use of regional interscalene anesthesia have been shown to provide effective and comfortable intraoperative conditions, while allowing for prolonged analgesia and quicker recovery with minimal side effects. The authors will discuss their approach to surgery, anesthesia, and recovery for outpatient shoulder reconstruction.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 275 Cambridge St,4th Floor, Boston, MA 02114 USA.
NR 19
TC 4
Z9 4
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0009-921X
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD SEP
PY 2001
IS 390
BP 10
EP 16
PG 7
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 468VJ
UT WOS:000170778600005
PM 11550855
ER

PT J
AU Harisinghani, MG
   Jhaveri, KS
   Weissleder, R
   Schima, W
   Saini, S
   Hahn, PF
   Mueller, PR
AF Harisinghani, MG
   Jhaveri, KS
   Weissleder, R
   Schima, W
   Saini, S
   Hahn, PF
   Mueller, PR
TI MRI contrast agents for evaluating focal hepatic lesions
SO CLINICAL RADIOLOGY
LA English
DT Review
DE liver; MRI; contrast agents
ID SUPERPARAMAGNETIC IRON-OXIDE; MALIGNANT LIVER-LESIONS; EUROPEAN
   PHASE-III; HEPATOCELLULAR-CARCINOMA; MN-DPDP; PATHOLOGICAL CORRELATION;
   NODULAR HYPERPLASIA; METASTASES; EFFICACY; IMAGES
AB Contrast-enhanced magnetic resonance imaging (MRI) has become an important tool in the detection and characterization of focal hepatic lesions especially when other investigations such as ultrasound (US) and computed tomography (CT) are inconclusive. The purpose of this pictorial review is to briefly summarize the properties of various MRI contrast agents used in hepatic imaging and to highlight their role in evaluation of focal hepatic lesions. (C) 2001 The Royal College of Radiologists.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA.
   Univ Vienna, Dept Radiol, Vienna, Austria.
RP Harisinghani, MG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Imaging & Intervent, White 270, Boston, MA 02114 USA.
NR 35
TC 20
Z9 21
U1 2
U2 9
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 SEP
PY 2001
VL 56
IS 9
BP 714
EP 725
DI 10.1053/crad.2001.0764
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 479FM
UT WOS:000171394400003
PM 11585393
ER

PT J
AU Verfaellie, M
   Keane, MM
   Cook, SP
AF Verfaellie, Mieke
   Keane, Margaret M.
   Cook, Shaun P.
TI The role of explicit memory processes in cross-modal priming: An
   investigation of stem completion priming in amnesia
SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE
LA English
DT Article
AB To clarify the role of explicit memory processes in cross-modal priming, two experiments examined the status of cross-modal stem completion priming in amnesia. Experiment 1 used a standard behavioral paradigm in which stems corresponding to studied and unstudied words were intermixed. Amnesic patients showed intact within- and cross-modal priming, but, in contrast to controls, they recognized very few of their completions as having been on the study list. This finding suggests that memorial awareness is not necessary for cross-modal priming to occur. Experiment 2 used a paradigm modeled after functional imaging studies, in which stems corresponding to studied and unstudied words were blocked. Amnesic patients showed intact within-modal priming, but impaired cross-modal priming. This finding is consistent with the notion that a blocked format induces voluntary retrieval strategies in normal participants.
C1 [Verfaellie, Mieke; Keane, Margaret M.; Cook, Shaun P.] Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA.
   [Verfaellie, Mieke; Keane, Margaret M.; Cook, Shaun P.] Boston Univ, Sch Med, Boston, MA 02118 USA.
   [Keane, Margaret M.] Wellesley Coll, Wellesley, MA 02181 USA.
RP Verfaellie, M (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr 151A, 150 S Huntington Ave, Boston, MA 02130 USA.
EM verf@bu.edu
FU NINDS [NS26985]; NIMH [MH57681]; Medical Research Service of the VA
   Healthcare System
FX This research was supported by NINDS Program Project Grant NS26985 and
   NIMH Grant MH57681 to Boston University and by the Medical Research
   Service of the VA Healthcare System. Correspondence should be addressed
   to M. Verfaellie, Memory Disorders Research Center (151A), Boston VA
   Healthcare System, 150 S. Huntington Avenue, Boston, MA 02130 (e-mail:
   verf@bu.edu).
NR 33
TC 5
Z9 5
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1530-7026
EI 1531-135X
J9 COGN AFFECT BEHAV NE
JI Cogn. Affect. Behav. Neurosci.
PD SEP
PY 2001
VL 1
IS 3
BP 222
EP 228
DI 10.3758/CABN.1.3.222
PG 7
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA V32LZ
UT WOS:000208954000002
PM 12467122
ER

PT J
AU Henin, A
   Otto, MW
   Reilly-Harrington, NA
AF Henin, A
   Otto, MW
   Reilly-Harrington, NA
TI Introducing flexibility in manualized treatments: Application of
   recommended strategies to the cognitive-behavioral treatment of bipolar
   disorder
SO COGNITIVE AND BEHAVIORAL PRACTICE
LA English
DT Article
ID WELL-BEING THERAPY; CLINICAL-PRACTICE; PANIC DISORDER; LIFE EVENTS;
   COMORBIDITY; PSYCHOTHERAPIES; DISCONTINUATION; DISSEMINATION;
   DEPRESSION; ILLNESS
AB Well-controlled treatment outcome studies have provided a wealth of evidence for the efficacy of specific manualized treatments for psychiatric disorders. In the face of these triumphs, there has been renewed attention to way, of modifying treatment manuals to better address the diverse needs of individuals, In this article we report on the application of recent recommendations for enhancing flexibility in manualized treatments. In particular we discuss the use of phases and modules of treatment applied according to case-formulation worksheets to address the needs of patients with bipolar disordor. Case examples are used to illustrate the application of this modular treatment approach.
C1 Massachusetts Gen Hosp, Bipolar Disorders Res Program, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Henin, A (reprint author), Massachusetts Gen Hosp, Bipolar Disorders Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA.
NR 40
TC 11
Z9 11
U1 0
U2 1
PU ASSOC ADV BEHAVIOR THERAPY
PI NEW YORK
PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA
SN 1077-7229
J9 COGN BEHAV PRACT
JI Cogn. Behav. Pract.
PD FAL
PY 2001
VL 8
IS 4
BP 317
EP 328
DI 10.1016/S1077-7229(01)80004-3
PG 12
WC Psychology, Clinical
SC Psychology
GA 639LV
UT WOS:000180631200004
ER

PT J
AU Tang, Y
   Yamashita, Y
   Abe, Y
   Namimoto, T
   Tsuchigame, T
   Takahashi, M
AF Tang, Y
   Yamashita, Y
   Abe, Y
   Namimoto, T
   Tsuchigame, T
   Takahashi, M
TI Congenital anomalies of the pancreaticobiliary tract: findings on MR
   cholangiopancreatography (MRCP) using half-Fourier-acquisition
   single-shot turbo spin-echo sequence (HASTE)
SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS
LA English
DT Article
DE magnetic resonance cholangiopancreatography; half-Fourier acquisition
   single-shot turbo spin-echo; pancreaticobiliary tract; congenital
   anomaly
ID CHOLEDOCHAL CYST; BILE-DUCT; CHOLANGIOGRAPHY; PANCREATITIS; ERCP
AB The clinical significance of magnetic resonance cholangiopancreatography (MRCP) using half-Fourier acquisition sin-le-shot turbo spine-cho (HASTE) in the evaluation of congenital anomalies of pancreaticobiliary tract was demonstrated in 56 patients (man: 31, women: 25; age: 0-60 years old, mean 15 years old) with suspected congenital anomalies of pancreaticobiliary tract. The image quality and characteristics were assessed. MRCP using HASTE with a phased array coil can be used as a non-invasive method for the evaluation of congenital anomalies of the pancreaticobiliary tracts. (C) 2001 Elsevier Science Ltd. All rights reserved.
C1 Kumamoto Univ, Sch Med, Dept Radiol, Kumamoto 860, Japan.
RP Tang, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Ctr Mol Imaging Res, Bldg 149,13th St,5408,CNY-5, Boston, MA 02129 USA.
NR 19
TC 4
Z9 4
U1 1
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-6111
J9 COMPUT MED IMAG GRAP
JI Comput. Med. Imaging Graph.
PD SEP-OCT
PY 2001
VL 25
IS 5
BP 423
EP 431
DI 10.1016/S0895-6111(00)00070-7
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 464DU
UT WOS:000170518600008
PM 11390197
ER

PT J
AU Mendez, MF
AF Mendez, MF
TI Visuospatial deficits with preserved reading ability in a patient with
   posterior cortical atrophy
SO CORTEX
LA English
DT Article
DE posterior cortical atrophy; dementia; alexia; reading; visual agnosia;
   spatial disorientation
ID PROGRESSIVE VISUAL AGNOSIA; ALZHEIMERS-DISEASE; BALINTS-SYNDROME; PURE
   ALEXIA; WORD-FORM; DEMENTIA; PATHWAYS; DISCONNECTION; IMPAIRMENT;
   DYSLEXIA
AB Visuospatial deficits are characteristic of posterior cortical atrophy (PCA). A 58 year old woman had progressive dressing apraxia and environmental disorientation but continued to read voraciously. Positron emission tomography revealed hypometabolism. of the occipitoparietal regions bilaterally, consistent with PCA. The symptoms suggested predominant dysfunction of the dorsal ("where") stream with abnormalities in visual localization and visuospatial integration; however, the patient also had a less pronounced apperceptive object agnosia. Further analysis of her preserved reading ability was performed. Familiar irregular words were read rapidly, but nonsense words were read slowly in a letter-by- letter fashion. She had a word superiority effect for embedded words and words with obscured letters but had difficulty reading stylized script or printing in unusual fonts. These findings suggested a dissociation between reading routes. Although the patient had a phonological dyslexia, her visuospatial processing was sufficient for access to preserved visual word forms for efficient lexical reading.
C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA.
   Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
   W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA.
RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Med Ctr, Neurobehav Unit, 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
NR 40
TC 13
Z9 13
U1 2
U2 4
PU MASSON DIVISIONE PERIODICI
PI MILAN
PA VIA FRATELLI BRESSAN 2, 20126 MILAN, ITALY
SN 0010-9452
J9 CORTEX
JI Cortex
PD SEP
PY 2001
VL 37
IS 4
BP 535
EP 543
DI 10.1016/S0010-9452(08)70592-6
PG 9
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 487AG
UT WOS:000171851100007
PM 11721864
ER

PT J
AU DeVita, MA
   Webb, SA
   Hurford, WE
   Truog, RD
   Wlody, GS
   Hayden, CT
   Sprung, CL
   Brilli, RJ
   Beals, DA
   Rothenberg, DM
   Friedman, AL
   Silverstein, DS
   Kaufman, DC
   Perkin, RM
   Rosenbaum, SH
   Cist, AFM
   Samotowka, M
   Teres, D
   Unkle, DW
   Burns, JP
   Wallace, TE
AF DeVita, MA
   Webb, SA
   Hurford, WE
   Truog, RD
   Wlody, GS
   Hayden, CT
   Sprung, CL
   Brilli, RJ
   Beals, DA
   Rothenberg, DM
   Friedman, AL
   Silverstein, DS
   Kaufman, DC
   Perkin, RM
   Rosenbaum, SH
   Cist, AFM
   Samotowka, M
   Teres, D
   Unkle, DW
   Burns, JP
   Wallace, TE
CA Ethics Comm Amer Coll Critical C
TI Recommendations for nonheartbeating organ donation
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE nonheartbeating organ donation; organ transplantation; ethics;
   end-of-life care; pediatric organ donation; death determination
ID TIME
C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
   Childrens Hosp, Charleston, SC USA.
   Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
   Vet Adm Med Ctr, Phoenix, AZ USA.
   Qual Management Dept, Phoenix, AZ USA.
   Hadassah Hebrew Univ Med Ctr, Dept Anesthesiol & Crit Care Med, Jerusalem, Israel.
   Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH USA.
   Univ Kentucky, Med Ctr, Lexington, KY USA.
   Rush Presbyterian St Lukes Med Ctr, Dept Anesthesiol, Chicago, IL 60612 USA.
   Yale Univ, Sch Med, Div Transplant Surg, New Haven, CT USA.
   Jersey Shore Med Ctr, Trauma SICU, Ctr Trauma, Neptune, NJ USA.
   Strong Mem Hosp, Surg ICU, Rochester, NY USA.
   E Carolina Univ, Brody Sch Med, Dept Pediat, Greenville, NC USA.
   Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06510 USA.
   Massachusetts Gen Hosp, Dept Pulm & Crit Care Med, Boston, MA 02114 USA.
   Trauma Surg Associates, Huntsville, AL USA.
   Astra ZENECA Pharmaceut, Westborough, MA USA.
   Int SOS, Trevose, PA USA.
   Childrens Hosp, Div Pediat Crit Care, MICU, Boston, MA 02115 USA.
   OSF St Anthony Med Ctr, Med Serv, Rockford, IL USA.
RP DeVita, MA (reprint author), Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
RI Hurford, William/G-6386-2013
OI Hurford, William/0000-0003-1201-0313
NR 28
TC 114
Z9 115
U1 0
U2 5
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 SEP
PY 2001
VL 29
IS 9
BP 1826
EP 1831
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA 472TE
UT WOS:000171000400029
ER

PT J
AU Chen, T
   Acker, JP
   Eroglu, A
   Cheley, S
   Bayley, H
   Fowler, A
   Toner, ML
AF Chen, T
   Acker, JP
   Eroglu, A
   Cheley, S
   Bayley, H
   Fowler, A
   Toner, ML
TI Beneficial effect of intracellular trehalose on the membrane integrity
   of dried mammalian cells
SO CRYOBIOLOGY
LA English
DT Article; Proceedings Paper
CT 38th Annual Meeting of the Society-for-Cryobiology
CY JUL   29, 2001
CL EDINBURGH, SCOTLAND
SP Soc Cryobiol
ID DESICCATION TOLERANCE; DRY LIPOSOMES; L-929 CELLS; WATER; STABILIZATION;
   VITRIFICATION; PRESERVATION; ANHYDROBIOSIS; STABILITY; MATRICES
AB Recently, there has been much interest in using trehalose and other small carbohydrates to preserve mammalian cells in the dried state as an alternative to cryopreservation. Here, we report on the successful preservation of plasma membrane integrity after drying, as a first step toward full preservation of mammalian cells. Trehalose was introduced into cells using a genetically engineered version of alpha-hemolysin, a pore-forming protein; the cells were then dried and stored for weeks at different temperatures with similar to90% recovery of the intact plasma membrane, we show that protection of the plasma membrane by internal trehalose is dose dependent and estimate the amount of internal trehalose required for adequate protection to be similar to10(10) molecules/cell, In addition, a minimal amount of water (similar to15 wt%) appears to be necessary. These results show that a key component of mammalian cells can be preserved in a dried state for weeks under mild conditions (-20degreesC and 5% relative humidity) and thereby suggest new approaches to preserving mammalian cells. (C) 2001 Elsevier Science (USA).
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn & Surg Serv, Boston, MA 02114 USA.
   Shriners Hosp Children, Boston, MA 02114 USA.
   Texas A&M Univ, Hlth Sci Ctr, Dept Med Biochem & Genet, College Stn, TX 77843 USA.
   Univ Massachusetts, Dept Mech Engn, Dartmouth, MA 02747 USA.
RP Chen, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn & Surg Serv, Boston, MA 02114 USA.
FU NIDDK NIH HHS [DK 46270]
NR 39
TC 112
Z9 126
U1 3
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0011-2240
J9 CRYOBIOLOGY
JI Cryobiology
PD SEP
PY 2001
VL 43
IS 2
BP 168
EP 181
DI 10.1006/cryo.2001.2360
PG 14
WC Biology; Physiology
SC Life Sciences & Biomedicine - Other Topics; Physiology
GA 525UP
UT WOS:000174092700008
PM 11846471
ER

PT J
AU Hinton, D
   Um, K
   Ba, P
AF Hinton, D
   Um, K
   Ba, P
TI A unique panic-disorder presentation among Khmer refugees: The sore-neck
   syndrome
SO CULTURE MEDICINE AND PSYCHIATRY
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; SOUTHEAST-ASIAN REFUGEES;
   ATAQUES-DE-NERVIOS; CAMBODIAN REFUGEES; PSYCHIATRIC-DIAGNOSIS;
   DEPRESSION; TRAUMA; SOMATIZATION; ANTHROPOLOGY; EXPERIENCES
AB This article describes a previously unreported cultural syndrome among Khmer refugees. This common presentation of distress centers on the complaint of a sore neck, the sufferer fearing that wind-and-blood pressure may burst the vessels in this area. During an acute episode, a Khmer endures many - if not all - of the following neck-and-head complaints: headache, blurry vision, a buzzing in the ear, and dizziness. While in the throes of the sore-neck attack, the patient frequently experiences palpitations as well as other symptoms of autonomic arousal, such as diaphoresis, shortness of breath, and trembling. A sufferer of sore-neck episodes often meets panic disorder criteria. In a clinic survey, thirty-five out of eighty-five patients (41%) were found to currently suffer the ``sore-neck syndrome'' (i.e., to have endured at least one episode in the last month), with almost all of these thirty-five patients (80%) fearing death during the acute event. The sore-neck syndrome represents a common and important way in which distress becomes embodied. The clinician must learn this body language; otherwise, the patient's communication of psychic, interpersonal, and physical pain goes unheard - and grave somatic suffering and disability unattended to - discounted as puzzling somatic complaints and unreasonable obsessionalism about blood pressure.
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,N Suffolk Counseling Ctr, Revere, MA 02151 USA.
RP Hinton, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,N Suffolk Counseling Ctr, Revere Site, Revere, MA 02151 USA.
NR 43
TC 39
Z9 39
U1 1
U2 7
PU KLUWER ACADEMIC PUBL
PI DORDRECHT
PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS
SN 0165-005X
J9 CULT MED PSYCHIAT
JI Cult. Med. Psychiatr.
PD SEP
PY 2001
VL 25
IS 3
BP 297
EP 316
DI 10.1023/A:1011848808980
PG 20
WC Anthropology; Psychiatry; Social Sciences, Biomedical
SC Anthropology; Psychiatry; Biomedical Social Sciences
GA 472PD
UT WOS:000170991900003
PM 11680477
ER

PT J
AU Kolodgie, FD
   Burke, AP
   Farb, A
   Gold, HK
   Yuan, JY
   Narula, J
   Finn, AV
   Virmani, R
AF Kolodgie, FD
   Burke, AP
   Farb, A
   Gold, HK
   Yuan, JY
   Narula, J
   Finn, AV
   Virmani, R
TI The thin-cap fibroatheroma: a type of vulnerable plaque - The major
   precursor lesion to acute coronary syndromes
SO CURRENT OPINION IN CARDIOLOGY
LA English
DT Review
ID UNSTABLE ANGINA-PECTORIS; ACUTE MYOCARDIAL-INFARCTION; SUDDEN ISCHEMIC
   DEATH; SMOOTH-MUSCLE CELLS; ATHEROSCLEROTIC LESIONS; CARDIAC DEATH;
   ANGIOGRAPHIC MORPHOLOGY; RISK-FACTORS; THROMBOSIS; EXPRESSION
AB While the concept of plaque 'vulnerability' implies a propensity towards thrombosis, the term vulnerable was originally intended to provide a morphologic description consistent with plaques that are prone to rupture. It is now known that the etiology of coronary thrombi is diverse and can arise from entities of plaque erosion or calcified nodules. These findings have prompted the search for more definitive terminology to describe precursor lesions associated with rupture, now referred to as thin-cap fibroatheromas. This review focuses on the thin-cap fibroatheroma, as a specific cause of acute coronary syndromes. To put these issues into current perspective, we need to revisit some of the older literature describing plaque morphology in stable and unstable angina, acute myocardial infarction, and sudden coronary death. The morphology, frequency, and precise location of these thin-cap fibroatheromas are further discussed in detail. Potential mechanisms of fibrous cap thinning are also addressed, in particular emerging data, which suggests the role of cell death "apoptosis" in cap atrophy. (C) 2001 Lippincott Williams & Wilkins, Inc.
C1 Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Washington, DC 20306 USA.
   Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA.
   Med Coll Penn & Hahnemann Univ, Dept Mol Cardiol, Philadelphia, PA USA.
   Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Virmani, R (reprint author), Armed Forces Inst Pathol, Dept Cardiovasc Pathol, 6825,16th St NW, Washington, DC 20306 USA.
FU NHLBI NIH HHS [R01 HL61799-02]
NR 54
TC 309
Z9 336
U1 1
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0268-4705
J9 CURR OPIN CARDIOL
JI Curr. Opin. Cardiol.
PD SEP
PY 2001
VL 16
IS 5
BP 285
EP 292
DI 10.1097/00001573-200109000-00006
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 481XE
UT WOS:000171545100006
PM 11584167
ER

PT J
AU Harding, SA
   Walters, DL
   Palacios, IF
   Oesterle, SN
AF Harding, SA
   Walters, DL
   Palacios, IF
   Oesterle, SN
TI Adjunctive pharmacotherapy for coronary stenting
SO CURRENT OPINION IN CARDIOLOGY
LA English
DT Review
ID THROMBOTIC THROMBOCYTOPENIC PURPURA; MULTICENTER RANDOMIZED TRIAL;
   ACTIVATED COAGULATION TIME; LOW-DOSE HEPARIN; ANTIPLATELET THERAPY;
   BALLOON ANGIOPLASTY; ISCHEMIC COMPLICATIONS; IIB/IIIA BLOCKADE;
   TICLOPIDINE TRIAL; PLATELET-FUNCTION
AB The use of coronary stents improves the outcomes of percutaneous coronary intervention (PCI). This has led to a rapid increase in their use. Coronary stenting is not without problems and is complicated by both early ischemic events and late restenosis. The combination of anticoagulation with unfractionated heparin (UFH) and the use of antiplatelet agents including aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors has led to a major reduction in early ischemic events after stenting. Low molecular weight heparin (LMWH) and direct thrombin inhibitors have a number of theoretical advantages over UFH. Their role as an adjunct to coronary stenting is still under investigation. Trials of systemic pharmacotherapy aimed at reducing in-stent restenosis have been consistently disappointing. Preliminary results of stents coated with agents that inhibit neointimal proliferation are extremely promising. The results of ongoing phase III trials of these coated stents are eagerly awaited. (C) 2001 Lippincott Williams & Wilkins, Inc.
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Oesterle, SN (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Bulfinch 105, Boston, MA 02114 USA.
RI Walters, Darren/A-7069-2011
NR 75
TC 17
Z9 17
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0268-4705
J9 CURR OPIN CARDIOL
JI Curr. Opin. Cardiol.
PD SEP
PY 2001
VL 16
IS 5
BP 293
EP 299
DI 10.1097/00001573-200109000-00007
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 481XE
UT WOS:000171545100007
PM 11584168
ER

PT J
AU Walters, DL
   Harding, SA
   Palacios, IF
   Oesterle, SN
AF Walters, DL
   Harding, SA
   Palacios, IF
   Oesterle, SN
TI The use of mechanical devices as adjuncts to intracoronary stenting
SO CURRENT OPINION IN CARDIOLOGY
LA English
DT Review
ID DIRECTIONAL CORONARY ATHERECTOMY; EXTRACTION CATHETER ATHERECTOMY;
   OPTICAL COHERENCE TOMOGRAPHY; SAPHENOUS-VEIN GRAFTS; INTRAVASCULAR
   ULTRASOUND; ROTATIONAL ATHERECTOMY; ARTERY DISEASE; BIFURCATION LESIONS;
   LUMEN SIZE; ANGIOGRAPHY
AB A number of mechanical adjuncts to intracoronary stenting are now available to the interventional cardiologist. These devices have assisted in the development of a safer and more effective stenting practice. Intravascular ultrasound-guided stenting has been shown to reduce the rate of subacute thrombosis and subsequent restenosis. It allows a greater appreciation of lesion structure and severity so that an appropriate intervention strategy can be devised. Debulking techniques may allow the optimal deployment of stents so that restenosis is reduced; however, the results of large randomized studies are still awaited. The use of thrombectomy and distal embolization protection devices is emerging as a safer alternate to stenting alone in difficult patient subsets, such as those with thrombus-laden lesions and degenerated vein grafts. Doppler and pressure wires may be useful in determining optimal stent deployment and predict subsequent patient outcomes. An understanding of the indications and limitations of these devices is of increasing importance to the interventional cardiologist as the coming decade threatens to yield an impressive array of high-tech innovations. (C) 2001 Lippincott Williams & Wilkins, Inc.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA.
RP Oesterle, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Bulfinch,105,55 Fruit St, Boston, MA 02114 USA.
RI Walters, Darren/A-7069-2011
NR 83
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0268-4705
J9 CURR OPIN CARDIOL
JI Curr. Opin. Cardiol.
PD SEP
PY 2001
VL 16
IS 5
BP 300
EP 305
DI 10.1097/00001573-200109000-00008
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 481XE
UT WOS:000171545100008
PM 11584169
ER

PT J
AU Lee, SP
   Ko, CW
AF Lee, SP
   Ko, CW
TI Gallstones
SO CURRENT OPINION IN GASTROENTEROLOGY
LA English
DT Article
ID ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; UNENHANCED HELICAL CT;
   GALL STONE DISEASE; GALLBLADDER-DISEASE; LAPAROSCOPIC CHOLECYSTECTOMY;
   MR CHOLANGIOGRAPHY; DEOXYCHOLIC-ACID; COFFEE CONSUMPTION;
   NATURAL-HISTORY; BILE
AB Gallstones are estimated to affect over 20 million people in the United States. Recent studies have clarified the role of various dietary components in gallstone disease. Also, insulin resistance has been demonstrated to be a risk factor for gallstones. Other research has focused on the pathophysiology of gallstones and on clarifying the underlying mechanisms of previously noted risk factors for gallstones. New techniques for the noninvasive diagnosis of bile duct stones continue to be developed and tested. These techniques include computed tomography and magnetic resonance cholangiography. The impact and appropriateness of laparoscopic cholecystectomy continue to debated, and studies point to both overuse and underuse of this operation in the management of the disease. Curr Opin Gastroenterol 2001, 17:463-467 (C) 2001 Lippincott Williams & Wilkins, Inc.
C1 VA Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA 98108 USA.
RP Lee, SP (reprint author), VA Puget Sound Hlth Care Syst, Div Gastroenterol, S-111-Gastro,1660 S Columbian Way, Seattle, WA 98108 USA.
NR 45
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0267-1379
J9 CURR OPIN GASTROEN
JI Curr. Opin. Gastroenterol.
PD SEP
PY 2001
VL 17
IS 5
BP 463
EP 467
DI 10.1097/00001574-200109000-00011
PG 5
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 466UG
UT WOS:000170664100011
PM 17031202
ER

PT J
AU Faller, DV
   Mentzer, SJ
   Perrine, SP
AF Faller, DV
   Mentzer, SJ
   Perrine, SP
TI Induction of the Epstein-Barr virus thymidine kinase gene with
   concomitant nucleoside antivirals as a therapeutic strategy for
   Epstein-Barr virus-associated malignancies
SO CURRENT OPINION IN ONCOLOGY
LA English
DT Review
ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; SOLID
   ORGAN-TRANSPLANTATION; ORAL HAIRY LEUKOPLAKIA; HUMAN LYMPHOCYTES-B;
   SODIUM-BUTYRATE; ACQUIRED IMMUNODEFICIENCY; RENAL-TRANSPLANTATION;
   HODGKINS-DISEASE; VIRAL-DNA; ACYCLOVIR THERAPY
AB Lymphoproliferative diseases (LPDs) associated with the Epstein-Barr virus (EBV) include non-Hodgkin lymphomas, which occur in the setting of immunosuppression, including that induced by human immunodeficiency virus, and posttransplant lymphoproliferative disorders. These LPDs are characterized by actively proliferating, latently infected EBV-positive B lymphocytes and often follow a rapidly progressive fatal clinical course. Pharmacologic treatment for herpesvirus infections has targeted the virus-specific enzyme, thymidine kinase (TK), with nucleoside analogs. The lack of viral TK expression in EBV-positive tumors, caused by viral latency, however, makes antiviral therapy alone ineffective as an antineoplastic therapy. Arginine butyrate selectively activates the EBV TK gene in latently infected EBV-positive tumor cells. We have developed a strategy for treatment of EBV-associated lymphomas using pharmacologic induction of the latent viral TK gene and enzyme in tumor cells using arginine butyrate, followed by treatment with ganciclovir. A phase I/II trial, using an intrapatient dose escalation of arginine butyrate combined with ganciclovir, is underway. This combination therapy has produced complete clinical responses in 5 of 10 previously refactory patients, with partial responses occurring in 2 additional patients. This virus-targeted antitumor strategy may provide a new therapeutic approach to EBV-associated neoplasms. Curr Opin Oncol 2001, 13:360-367 (C) 2001 Lippincott Williams & Wilkins, Inc.
C1 Boston Univ, Sch Med, Canc Res Ctr, Boston, MA 02118 USA.
   Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
   Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Faller, DV (reprint author), Boston Univ, Sch Med, Canc Res Ctr, K-701,715 Albany St, Boston, MA 02118 USA.
FU NCI NIH HHS [CA84193, CA85687]
NR 101
TC 53
Z9 56
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8746
J9 CURR OPIN ONCOL
JI Curr. Opin. Oncol.
PD SEP
PY 2001
VL 13
IS 5
BP 360
EP 367
DI 10.1097/00001622-200109000-00008
PG 8
WC Oncology
SC Oncology
GA 466UK
UT WOS:000170664400008
PM 11555713
ER

PT J
AU James, JA
   Harley, JB
   Scofield, RH
AF James, JA
   Harley, JB
   Scofield, RH
TI Role of viruses in systemic lupus erythematosus and Sjogren syndrome
SO CURRENT OPINION IN RHEUMATOLOGY
LA English
DT Review
ID EPSTEIN-BARR-VIRUS; HEPATITIS-C VIRUS; PARVOVIRUS B19 INFECTION;
   I-ASSOCIATED MYELOPATHY; EXTRAHEPATIC MANIFESTATIONS;
   CYTOMEGALOVIRUS-INFECTION; HUMAN RETROVIRUS-5; SALIVARY-GLANDS;
   SICCA-SYNDROME; RISK-FACTORS
AB Systemic lupus erythematosus and Sjogren syndrome remain elusive in the description of their underlying etiologic causes and pathogenic mechanisms. Although underlying genetic predisposition appears to contribute to both diseases based on twin and other genetic studies, additional factors must play a role. Over the decades additional factors, such as hormonal influence, UV light, environmental exposures (eg, silica, solvents), and infectious agents have been postulated to play a role. Over the past few years additional information has been published concerning roles of various infectious agents in both lupus and Sjogren syndrome. Although the understanding of this field is still incomplete, significant advances are being made.(C) 2001 Lippincott Williams & Wilkins, Inc.
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 Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 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 [AI31584]; NIAMS NIH HHS [AR01981, AR45084, AR45451]
NR 81
TC 51
Z9 54
U1 1
U2 2
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 SEP
PY 2001
VL 13
IS 5
BP 370
EP 376
DI 10.1097/00002281-200109000-00005
PG 7
WC Rheumatology
SC Rheumatology
GA 477AY
UT WOS:000171262000005
PM 11604590
ER

PT J
AU Sheridan, RL
AF Sheridan, RL
TI In brief
SO CURRENT PROBLEMS IN SURGERY
LA English
DT Editorial Material
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Shriners Burns Hosp, Burn Surg Serv, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Sheridan, RL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY, INC
PI ST LOUIS
PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA
SN 0011-3840
J9 CURR PROB SURG
JI Curr. Probl. Surg.
PD SEP
PY 2001
VL 38
IS 9
BP 647
EP 656
PG 10
WC Surgery
SC Surgery
GA 479BP
UT WOS:000171384300002
ER

PT J
AU Sheridan, RL
AF Sheridan, RL
TI Comprehensive treatment of burns
SO CURRENT PROBLEMS IN SURGERY
LA English
DT Review
ID TOXIC EPIDERMAL NECROLYSIS; RESUSCITATION FLUID VOLUME;
   HYPERBARIC-OXYGEN THERAPY; GRAFT DONOR SITES; CULTURED AUTOLOGOUS
   KERATINOCYTES; POSITIVE PRESSURE VENTILATION; THERMALLY INJURED
   PATIENTS; ACUTE INHALATION INJURY; MULTIPLE ORGAN FAILURE; LARGE
   CUTANEOUS BURNS
C1 Massachusetts Gen Hosp, Div Trauma & Burns, Boston, MA 02114 USA.
   Shriners Burns Hosp, Burn Surg Serv, Boston, MA USA.
   Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
RP Sheridan, RL (reprint author), Massachusetts Gen Hosp, Div Trauma & Burns, Boston, MA 02114 USA.
NR 323
TC 17
Z9 19
U1 0
U2 3
PU MOSBY, INC
PI ST LOUIS
PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA
SN 0011-3840
J9 CURR PROB SURG
JI Curr. Probl. Surg.
PD SEP
PY 2001
VL 38
IS 9
BP 657
EP 756
DI 10.1016/S0011-3840(01)70019-6
PG 100
WC Surgery
SC Surgery
GA 479BP
UT WOS:000171384300003
PM 11568825
ER

PT J
AU Navarro, RE
   Shim, EY
   Kohara, Y
   Singson, A
   Blackwell, TK
AF Navarro, RE
   Shim, EY
   Kohara, Y
   Singson, A
   Blackwell, TK
TI cgh-1, a conserved predicted RNA helicase required for gametogenesis and
   protection from physiological germline apoptosis in C-elegans
SO DEVELOPMENT
LA English
DT Article
DE germline; apoptosis; RNA helicase; oocyte; Caenorhabditis elegans; P
   granules; germ plasm
ID SEX-DETERMINATION GENE; DEAD-BOX PROTEIN; CAENORHABDITIS-ELEGANS;
   SACCHAROMYCES-CEREVISIAE; CELL-DEATH; DROSOPHILA; OOCYTES; LINE;
   INTERFERENCE; GRANULES
AB A high frequency of apoptosis is a conserved hallmark of oocyte development. In C. elegans, about half of all developing oocytes are normally killed by a physiological germline-specific apoptosis pathway, apparently so that they donate cytoplasm to the survivors. We have investigated the functions of CGH-1, the C. elegans ortholog of the predicted RNA helicase ste13/ME31B/RCK/p54, which is germline-associated in metazoans and required for sexual reproduction in yeast. We show that CGH-1 is expressed specifically in the germline and early embryo, and is localized to P granules and other possible mRNA-protein particles. cgh-1 is required for oocyte and sperm function. It is also needed to prevent the physiological germline apoptosis mechanism killing essentially all developing oocytes, making lack of cgh-1 function the first stimulus identified that can trigger this mechanism. We conclude that cgh-1 and its orthologs may perform conserved functions during gametogenesis, that in C. elegans certain aspects of oocyte development are monitored by the physiological germline apoptosis pathway, and that similar surveillance mechanisms may contribute to germline apoptosis in other species.
C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA.
   Rutgers State Univ, Waksman Inst, Piscataway, NJ 08854 USA.
   Japan Sci & Technol Corp, Genome Biol Lab, Natl Inst Genet, Mishima, Shizuoka 4118540, Japan.
RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02215 USA.
NR 57
TC 104
Z9 107
U1 0
U2 2
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 SEP
PY 2001
VL 128
IS 17
BP 3221
EP 3232
PG 12
WC Developmental Biology
SC Developmental Biology
GA 480TJ
UT WOS:000171478600001
PM 11546739
ER

PT J
AU Lin, YF
   Liu, AP
   Zhang, SB
   Ruusunen, TJ
   Kreidberg, JA
   Peltoketo, H
   Drummond, I
   Vainio, S
AF Lin, YF
   Liu, AP
   Zhang, SB
   Ruusunen, TJ
   Kreidberg, JA
   Peltoketo, H
   Drummond, I
   Vainio, S
TI Induction of ureter branching as a response to Wnt-2b signaling during
   early kidney organogenesis
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE Wnt signaling; inductive interactions; epithelial-mesenchymal
   interactions; kidney development; branching morphogenesis
ID EPITHELIAL TRANSFORMATION; METANEPHRIC MESENCHYME; EMBRYONIC KIDNEY;
   SONIC-HEDGEHOG; GENE FAMILY; EXPRESSION; MOUSE; MORPHOGENESIS; PATHWAY;
   TUBULE
AB Epithellial-mesenchymal tissue interactions play a central role in vertebrate organogenesis, but the molecular mediators and mechanisms of these morphogenetic interactions are still not well characterized. We report here on the expression pattern of Wnt-2b during mouse organogenesis and on tests of its function in epithelial-mesenchymal interactions during kidney development. Wnt-2b is expressed in numerous developing organs in the mouse embryo, including the kidney, lung, salivary gland, gut, pancreas, adrenal gland, and genital tubercle. Additional sites of expression include the branchial arches and craniofacial placodes such as the eye and ear. The data suggest that the expression of Wnt-2b is associated with organs regulated by epithelial-mesenchymal interactions. It is typically localized in the capsular epithelium or peripheral mesenchymal cells of organ rudiments, e.g., the perinephric mesenchymal cells in the region of the presumptive renal stroma in the developing kidney at E11.5. Functional studies of the kidney demonstrate that cells expressing Wnt-2b are not capable of inducing tubule formation but instead stimulate ureter development. Incubation of isolated ureteric buds on such cells supports bud growth and branching. In addition, recombination of Wnt-2b-pretreated ureteric bud tissue with isolated nephrogenic mesenchyme results in a recovery of organogenesis and the expression of epithelial genes within the reconstituted organ explant. Lithium, a known activator of Wnt signaling (Hedgepeth et al. [1997] Dev Biol 185:82-91), is also sufficient to promote ureter branching in the reconstituted kidney in a comparable manner to Wnt-2b signaling, whereas Wnt-4, which induces tubules, neither supports the growth of a ureteric bud nor leads to reconstitution of the ureteric bud with the kidney mesenchyme. We conclude that Wnt-2b may act in the mouse kidney as an early mesenchymal signal controlling morphogenesis of epithelial tissue, and that the Wnt pathway may regulate ureter branching directly. In addition, Wnt signals in the kidney differ qualitatively and are specific to either the epithelial ureteric bud or the kidney mesenchyme. (C) 2001 Wiley-Liss, Inc.
C1 Oulu Univ, Dept Biochem, FIN-90014 Oulu, Finland.
   Oulu Univ, Bioctr, Oulu, Finland.
   Massachusetts Gen Hosp, Renal Unit, CNY 8000, Charlestown, MA USA.
   Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA USA.
   Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   Oulu Univ, Fac Sci, Dept Biochem, Oulu, Finland.
   Oulu Univ, Fac Med, Dept Biochem, Oulu, Finland.
RP Vainio, S (reprint author), Oulu Univ, Dept Biochem, POB 3000, FIN-90014 Oulu, Finland.
EM Seppo.Vainio@oulu.fi
FU NIDDK NIH HHS [DK54711, DK53093]
NR 48
TC 45
Z9 46
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 1058-8388
J9 DEV DYNAM
JI Dev. Dyn.
PD SEP
PY 2001
VL 222
IS 1
BP 26
EP 39
DI 10.1002/dvdy.1164
PG 14
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA 465LA
UT WOS:000170589400003
PM 11507767
ER

PT J
AU El Mkadem, SA
   Lautier, C
   Macari, F
   Molinari, N
   Lefebvre, P
   Renard, E
   Gris, JC
   Cros, G
   Daures, JP
   Bringer, J
   White, MF
   Grigorescu, F
AF El Mkadem, SA
   Lautier, C
   Macari, F
   Molinari, N
   Lefebvre, P
   Renard, E
   Gris, JC
   Cros, G
   Daures, JP
   Bringer, J
   White, MF
   Grigorescu, F
TI Role of allelic variants Gly972Arg of IRS-1 and Gly1057Asp of IRS-2 in
   moderate-to-severe insulin resistance of women with polycystic ovary
   syndrome
SO DIABETES
LA English
DT Article
ID RECEPTOR SUBSTRATE-2; GENE; PATHOGENESIS; POLYMORPHISM; MUTATIONS;
   SECRETION; PROMOTER; SYSTEM
AB To assess the role of insulin receptor, insulin receptor substrate (IRS)-1, and IRS-2 genes in insulin resistance, we explored the genomic DNA in women with polycystic ovary syndrome (PCOS) and a variable degree (mean +/- SE) of insulin resistance (homeostasis model assessment index for insulin resistance [HOMA(IR)] 3.2 +/- 0.6, n = 53; control subjects 1.56 +/- 0.34, n = 102) using direct sequencing. Whereas no novel mutations were found in these genes, gene-dosage effects were found on fasting insulin for the Gly972Arg IRS-1 variant and on 2-h plasma glucose for the GIy1057Asp IRS-2 variant. The Gly972Arg IRS-1 variant was more prevalent in insulin-resistant patients compared with non-insulin-resistant individuals or control subjects (39.3 vs. 4.0 and 16.6%, P < 0.0031, respectively). A multivariate model that included BMI as a variable revealed significant effects of the Gly1057Asp IRS-2 variant on insulin resistance (P < 0.016, odds ratio [OR] 7.2, 95% CI 1.29-43.3). HOMA(IR) was higher in carriers of both IRS variants than in those with IRS-2 mutations only or those with wild-type variants (6.2 +/- 2.3, 2.8 +/- 0.5, and 1.8 +/- 0.2, respectively; P < 0.01), and it was significantly associated with this genotype (P < 0.0085, OR 1.7, 95% CI 1.09-2.99). We conclude that polymorphic alleles of both IRS-1 and IRS-2, alone or in combination, may have a functional impact on the insulin-resistant component of PCOS.
C1 Univ Montpellier, Inst Rech Clin, Mol Endocrinol Lab, F-34093 Montpellier 5, France.
   Lapeyronie Hosp, Dept Endocrinol, Montpellier, France.
   Joslin Diabet Ctr, Boston, MA 02215 USA.
RP Grigorescu, F (reprint author), Univ Montpellier, Inst Rech Clin, Mol Endocrinol Lab, 641 Ave Doyen Gaston Giraud, F-34093 Montpellier 5, France.
RI macari, francoise/E-9941-2014
NR 20
TC 81
Z9 85
U1 0
U2 0
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA
SN 0012-1797
J9 DIABETES
JI Diabetes
PD SEP
PY 2001
VL 50
IS 9
BP 2164
EP 2168
DI 10.2337/diabetes.50.9.2164
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 466QU
UT WOS:000170656900027
PM 11522686
ER

PT J
AU Wolpert, HA
   Anderson, B
AF Wolpert, HA
   Anderson, B
TI Young adults with diabetes - Need for a new treatment paradigm
SO DIABETES CARE
LA English
DT Editorial Material
ID SELF-CARE; MELLITUS; TRANSITION
C1 Joslin Diabet Ctr, Sect Adult Diabet, Boston, MA 02215 USA.
   Joslin Diabet Ctr, Mental Hlth & Behav Res Unit, Boston, MA 02215 USA.
RP Wolpert, HA (reprint author), Joslin Diabet Ctr, Sect Adult Diabet, 1 Joslin Pl, Boston, MA 02215 USA.
NR 12
TC 27
Z9 27
U1 1
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA
SN 0149-5992
J9 DIABETES CARE
JI Diabetes Care
PD SEP
PY 2001
VL 24
IS 9
BP 1513
EP 1514
DI 10.2337/diacare.24.9.1513
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 466QT
UT WOS:000170656800001
PM 11522689
ER

PT J
AU Zrebiec, J
AF Zrebiec, J
TI A national job analysis of certified diabetes educators by the National
   Certification Board for Diabetes Educators
SO DIABETES EDUCATOR
LA English
DT Article
AB Purpose. The job analysis described in this report was conducted by the National Certification Board for Diabetes Educators (NCBDE) to (1) provide a basis for documenting the continuing validity of the certified diabetes educator examination (CDE), (2) define areas that should be assessed in future certification examinations, and (3) ensure that the content of certification examinations is job related.
   Methods A diabetes educator job task list was developed and used to create a job analysis survey. The survey was distributed randomly to 1079 CDEs throughout the United States.
   Results Of the 1079 surveys that were distributed, 327 were suitable for analysis, with relevant demographic subgroups adequately represented. An examination matrix and detailed content outline were constructed from the survey data that will be used by the NCBDE to assemble future test forms.
   Conclusions Specifications for the CDE examination were developed that were directly related to the important activities that diabetes educators perform. Future forms of the CDE examination will be matched to job-related, criterion-referenced test specifications and will have strong evidence of content validity. Future fortes of the exam will contain 200 items at specified cognitive levels with a representative sampling of tasks within 4 core areas front the detailed content outline.
C1 Natl Certificat Board Diabet Educators, Arlington Hts, IL USA.
RP Zrebiec, J (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
NR 3
TC 2
Z9 2
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 SEP-OCT
PY 2001
VL 27
IS 5
BP 694
EP 702
DI 10.1177/014572170102700510
PG 9
WC Endocrinology & Metabolism; Public, Environmental & Occupational Health
SC Endocrinology & Metabolism; Public, Environmental & Occupational Health
GA 473WU
UT WOS:000171072600009
PM 12212019
ER

PT J
AU Elliott, D
   Pitman, MB
AF Elliott, D
   Pitman, MB
TI Malignant melanoma with a myxoid stroma: A diagnostic pitfall on
   fine-needle aspiration biopsy
SO DIAGNOSTIC CYTOPATHOLOGY
LA English
DT Article
DE cytology; myxoid; melanoma; sarcoma; pitfall
ID METASTATIC MELANOMA; SOFT-TISSUE; S100 PROTEIN; CYTOLOGY;
   IMMUNOCYTOCHEMISTRY; LESIONS; TUMORS
AB Malignant melanoma (MM), both primary and metastatic, may be associated with a prominent myxoid stromal reaction causing diagnostic confusion on fine-needle aspiration biopsy (FNAB), most often with sarcomas that demonstrate a myxoid stroma, particularly malignant peripheral nerve sheath tumor (MPNST). We present a case of a 32-yr-old man with no past medical history who presented with a unilateral neck mass clinically suspicious for lymphoma. FNAB produced a specimen composed of large sheets of anaplastic cells encased in a my-void stroma that was S100 and vimentin-positive but HMB-45-negative. A diagnosis of MPNST was made. Excision demonstrated a metastatic MM of unknown primary, with a prominent myxoid stromal reaction. A repeat HMB-45 was again negative. Electron microscopy demonstrated intracytoplasmic melanasomes and cisternae of rough endoplasmic reticulum with intracisternal parallel tubules, confirming the diagnosis. Although HMB-45 is typically negative in both tumors, S100 should be strongly positive in myxoid MM and only focal in MPNST. (C) 2001 Wiley-Liss, Inc.
C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Pitman, MB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 14 Fruit St, Boston, MA 02114 USA.
NR 32
TC 8
Z9 8
U1 0
U2 0
PU WILEY-LISS
PI NEW YORK
PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 8755-1039
J9 DIAGN CYTOPATHOL
JI Diagn. Cytopathol.
PD SEP
PY 2001
VL 25
IS 3
BP 185
EP 190
DI 10.1002/dc.2034
PG 6
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 467HB
UT WOS:000170695400009
PM 11536443
ER

PT J
AU Lark, RL
   Saint, S
   Chenoweth, C
   Zemencuk, JK
   Lipsky, BA
   Plorde, JJ
AF Lark, RL
   Saint, S
   Chenoweth, C
   Zemencuk, JK
   Lipsky, BA
   Plorde, JJ
TI Four-year prospective evaluation of community-acquired bacteremia:
   Epidemiology, microbiology, and patient outcome
SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
LA English
DT Article
ID POSITIVE BLOOD CULTURES; CENTRAL VENOUS CATHETERS; URINARY-TRACT
   INFECTION; CLINICAL-SIGNIFICANCE; COMPREHENSIVE ANALYSIS; STREAM
   INFECTION; 500 EPISODES; FUNGEMIA; ADULTS; METAANALYSIS
AB The objectives of this study were to (1) describe the epidemiology and microbiology of community-acquired bacteremia; (2) determine the crude mortality associated with such infections; and (3) identify independent predictors of mortality. All patients with clinically significant community-acquired bacteremia admitted to a university-affiliated Veterans Affairs medical center from January 1994 through December 1997 were evaluated. During the study period, 387 bacteremic episodes occurred in 334 patients. Staphylococcus aureus, Escherichia coli, and coagulase-negative staphylococci were the most commonly isolated organisms, the most frequent sources were the urinary tract and intravascular catheters. Approximately 14% of patients died. Patient characteristics independently associated with increased mortality included shock (OR 3.7, p = 0.02) and renal failure (OR 4.0, p = 0.003). The risk of death was also higher in those whose source was pneumonia (OR 6.3, p = 0.03) or an intra-abdominal site (OR 10.7, p = 0.02), or if multiple sources were identified (OR 13.4, p = 0.003). Community-acquired bacteremia is often device-related and may be preventable. Strategies that have been successful in preventing nosocomial device-related bacteremia should be adapted to the outpatient setting. (C) 2001 Elsevier Science Inc. All rights reserved.
C1 Univ Michigan, Dept Internal Med, Div Internal Med, Ann Arbor, MI 48109 USA.
   Univ Michigan, Dept Control & Epidemiol, Ann Arbor, MI 48109 USA.
   Vet Affairs Puget Sound Healthcare Syst, Seattle Div, Seattle, WA USA.
   Univ Washington, Dept Med, Div Infect Dis, Seattle, WA 98195 USA.
   Ann Arbor VA Hlth Serv Res & Dev Program, Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA.
   Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA.
   Univ Michigan, Dept Internal Med, Div Gen Med, Ann Arbor, MI 48109 USA.
RP Chenoweth, C (reprint author), Univ Michigan, Dept Internal Med, Div Internal Med, Ann Arbor, MI 48109 USA.
OI Lipsky, Benjamin A./0000-0001-9886-5114
NR 18
TC 50
Z9 50
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 0732-8893
J9 DIAGN MICR INFEC DIS
JI Diagn. Microbiol. Infect. Dis.
PD SEP-OCT
PY 2001
VL 41
IS 1-2
BP 15
EP 22
DI 10.1016/S0732-8893(01)00284-X
PG 8
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA 488LY
UT WOS:000171937700002
PM 11687309
ER

PT J
AU Meyer, JH
   Lake, R
   Elashoff, JD
AF Meyer, JH
   Lake, R
   Elashoff, JD
TI Postcibal gastric emptying of pancreatin pellets - Effects of dose and
   meal oil
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE pancreatic insufficiency; steatorrhea; treatment
ID CYSTIC-FIBROSIS; COATED MICROSPHERES; ENZYME SUPPLEMENTS; TREATED
   PATIENTS; SOLID-LIQUID; CANINE MODEL; INSUFFICIENCY; FAT; COLONOPATHY;
   ABSORPTION
AB To treat pancreatic exocrine insufficiency, physicians often prescribe enterically coated pellets of pancreatin to be taken with meals. The pellets are only partially effective in correcting the digestion and absorption of fat. We sought to determine in normal subjects whether emptying of pellets from the postcibal stomach was dose-related and whether the gastric emptying of lipophilic Creon-20 or Pancrease was altered by the presence or the absence of oil in a meal. Gastric emptying of pellets surface-labeled with In-113m or Tc-99m was followed with a gamma camera for 300 min after isocaloric meals. From our observations, we concluded that gastric emptying of 0.28-1.12 g of 1-mm or 2-mm pellets was dose-related (P < 0.01) and emptying of neither Creon-20 nor Pancrease was much affected by oil in the meal.
C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA.
   VA Greater Los Angeles Healthcare Syst, Dept Nucl Med, Los Angeles, CA USA.
   Cedars Sinai Med Ctr, Biostat Core Res Inst, Los Angeles, CA 90048 USA.
   Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
RP Meyer, JH (reprint author), W Los Angeles Vet Affairs Med Ctr, Rm 105,Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
NR 32
TC 4
Z9 4
U1 1
U2 5
PU KLUWER ACADEMIC/PLENUM PUBL
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD SEP
PY 2001
VL 46
IS 9
BP 1846
EP 1852
DI 10.1023/A:1010666510755
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 474PN
UT WOS:000171116200005
PM 11575435
ER

PT J
AU Huerta, S
   Srivatsan, ES
   Venkatasan, N
   Livingston, EH
AF Huerta, S
   Srivatsan, ES
   Venkatasan, N
   Livingston, EH
TI Human colon cancer cells deficient in DCC produce abnormal transcripts
   in progression of carcinogenesis
SO DIGESTIVE DISEASES AND SCIENCES
LA English
DT Article
DE DCC; colon cancer; SW620; SW480
ID ADHESION MOLECULE; COLORECTAL-CANCER; TUMOR PROGRESSION; GENE;
   EXPRESSION; PROTEIN; METASTASES; CARCINOMA; PROGNOSIS
AB Expressive loss of the tumor suppressor deleted in colon cancer (DCC) may be superior to lymph node status in predicting patient survival for intermediate stage colon cancer. A polymerase chain reaction (PCR)-based method for detecting DCC would be ideal as a prognostic indicator. DCC is an alternatively spliced molecule; thus, reliability of a PCR test for DCC will depend on amplifying only those regions of the molecule that are lost in the progression of colon cancer. For this reason, we studied a colon cancer cell line model at different stages of tumor progression to determine the alternative splice pattern for DCC. A commercially available colon cancer cell line system at different stages of tumor progression was used to identify which DCC exons are lost by western blot analysis, PCR, and RT-PCR techniques. Colon cancers express abnormal DCC transcripts. The proximal and distal exons are present (exons 2 and 28-29). Exons located in the center of the molecule are absent (6-7 and 18-23). This correlated to DCC protein loss in the cell lines. For clinical utility as a disease marker, exons in the middle portion of the DCC molecule that are spliced out should be utilized. Amplification of the proximal and distal regions will result in falsely concluding that DCC is present when its protein product is not expressed.
C1 W Los Angeles UCLA Sch Med, VAGLAHS, Div Gen Surg, Los Angeles, CA USA.
RP Livingston, EH (reprint author), W Los Angeles Vet Affairs Med Ctr, Surg Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
NR 27
TC 10
Z9 12
U1 0
U2 0
PU KLUWER ACADEMIC/PLENUM PUBL
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0163-2116
J9 DIGEST DIS SCI
JI Dig. Dis. Sci.
PD SEP
PY 2001
VL 46
IS 9
BP 1884
EP 1891
DI 10.1023/A:1010626929411
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 474PN
UT WOS:000171116200010
PM 11575440
ER

PT J
AU Cuajungco, MP
   Leyne, M
   Mull, J
   Gill, SP
   Gusella, JF
   Slaugenhaupt, SA
AF Cuajungco, MP
   Leyne, M
   Mull, J
   Gill, SP
   Gusella, JF
   Slaugenhaupt, SA
TI Cloning, characterization, and genomic structure of the mouse Ikbkap
   gene
SO DNA AND CELL BIOLOGY
LA English
DT Article
ID POLYMERASE-II HOLOENZYME; NF-KAPPA-B; IKK COMPLEX; PROTEIN; ELONGATOR;
   COMPONENT; IKAP
AB Our laboratory recently reported that mutations in the human I-kappaB kinase-associated protein (IKBYAP) gene are responsible for familial dysautonomia (FD). Interestingly, amino acid substitutions in the IKAP correlate with increased risk for childhood bronchial asthma. Here, we report the cloning and genomic characterization of the mouse Ikbkap gene, the homolog of human IKBKAP. Like its human counterpart, Ikbkap encodes a protein of 1332 amino acids with a molecular weight of approximately 150 kDa. The Ikbkap gene product, Ikap, contains 37 exons that span approximately 51 kb. The protein shows 80% amino acid identity with human IKAP. It shows very high conservation across species and is homologous to the yeast Elp1/Iki3p protein, which is a member of the Elongator complex. The Ikbkap gene maps to chromosome 4 in a region that is syntenic to human chromosome 9q31.3. Because no animal model of FD currently exists, cloning of the mouse Ikbkap gene is an important first step toward creating a mouse model for FD. In addition, cloning of Ikbkap is crucial to the characterization of the putative mammalian Elongator complex.
C1 Harvard Inst Human Genet, Boston, MA USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Slaugenhaupt, SA (reprint author), HIM Bldg,Rm 422,77 Ave Louis Pasteur, Boston, MA 02115 USA.
RI Cuajungco, Math/B-2647-2008
OI Cuajungco, Math/0000-0003-0749-9564
FU NINDS NIH HHS [NS36326]
NR 15
TC 19
Z9 20
U1 0
U2 1
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 1044-5498
J9 DNA CELL BIOL
JI DNA Cell Biol.
PD SEP
PY 2001
VL 20
IS 9
BP 579
EP 586
DI 10.1089/104454901317094990
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity
GA 490BU
UT WOS:000172031000006
PM 11747609
ER

PT J
AU Schlozman, SC
AF Schlozman, SC
TI Too sad to learn?
SO EDUCATIONAL LEADERSHIP
LA English
DT Article
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
   Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA.
RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT
PI ALEXANDRIA
PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0013-1784
J9 EDUC LEADERSHIP
JI Educ. Leadership
PD SEP
PY 2001
VL 59
IS 1
BP 80
EP 81
PG 2
WC Education & Educational Research
SC Education & Educational Research
GA 499DF
UT WOS:000172555200016
ER

PT J
AU Davy, A
   Bello, P
   Thierry-Mieg, N
   Vaglio, P
   Hitti, J
   Doucette-Stamm, L
   Thierry-Mieg, D
   Reboul, J
   Boulton, S
   Walhout, AJM
   Coux, O
   Vidal, M
AF Davy, A
   Bello, P
   Thierry-Mieg, N
   Vaglio, P
   Hitti, J
   Doucette-Stamm, L
   Thierry-Mieg, D
   Reboul, J
   Boulton, S
   Walhout, AJM
   Coux, O
   Vidal, M
TI A protein-protein interaction map of the Caenorhabditis elegans 26S
   proteasome
SO EMBO REPORTS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; PROTEOLYSIS; COMPLEX; LINK
AB The ubiquitin-proteasome proteolytic pathway is pivotal in most biological processes. Despite a great level of information available for the eukaryotic 26S proteasome-the protease responsible for the degradation of ubiquitylated proteins-several structural and functional questions remain unanswered. To gain more insight into the assembly and function of the metazoan 26S proteasome, a two-hybrid-based protein interaction map was generated using 30 Caenorhabditis elegans proteasome subunits. The results recapitulate interactions reported for other organisms and reveal new potential interactions both within the 19S regulatory complex and between the 19S and 20S subcomplexes. Moreover, novel potential proteasome interactors were identified, including an E3 ubiquitin ligase, transcription factors, chaperone proteins and other proteins not yet functionally annotated. By providing a wealth of novel biological hypotheses, this interaction map constitutes a framework for further analysis of the ubiquitin-proteasome pathway in a multicellular organism amenable to both classical genetics and functional genomics.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
   CRBM, CNRS UPR 1086, IFR 24, F-34293 Montpellier, France.
   IMAG, Lab LSR, F-38041 Grenoble, France.
   Genome Therapeut Corp, Waltham, MA 02453 USA.
   NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Vidal, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
RI Coux, Olivier/B-3406-2010; Thierry-Mieg, Nicolas/M-6007-2014; Reboul,
   Jerome/P-9103-2016; 
OI Coux, Olivier/0000-0001-8455-3849; Reboul, Jerome/0000-0002-5513-4546;
   Vaglio, Philippe/0000-0003-2900-5596; Walhout,
   Marian/0000-0001-5587-3608
FU NCI NIH HHS [7R33 CA81658-02, P01 CA080111, P01CA80111-02]; NHGRI NIH
   HHS [R01 HG001715, 5R01HG01715-02]; PHS HHS [232]
NR 30
TC 128
Z9 138
U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD SEP
PY 2001
VL 2
IS 9
BP 821
EP 828
DI 10.1093/embo-reports/kve184
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 477MM
UT WOS:000171287400018
PM 11559592
ER

PT J
AU Chen, HC
AF Chen, HC
TI Intravenous calcium replacement for asymptomatic hypocalcemia of
   critical illness
SO ENDOCRINOLOGIST
LA English
DT Review
ID ADMINISTRATION INCREASES; MORTALITY; SHOCK; RATS
AB Background: No studies have been performed to determine if intravenous calcium replacement in critically ill patients with mild, asymptomatic hypocalcemia improves clinical outcome.
   Methods: Case-control study of patients in the medical surgical intensive care unit of the San Francisco Veterans Affairs Medical Center. Two groups of patients were studied; one group consisting of all 15 patients who received intravenous calcium infusions in May 1999, and a control group consisting of an equal number of patients matched for severity of illness, as determined by Simplified Acute Physiology Score (SAPS II). Length of hospital stay and in-hospital mortality were calculated for each group. Results: The two groups did not differ significantly in baseline characteristics or severity of illness. The two groups also did not differ in mean serum calcium concentrations or degree of hypocalcemia during their hospital course. The calcium replacement group, however, had a longer hospital stay (20.7 vs. 12.4 days, p = 0.02). Conclusions: Intravenous calcium. replacement in mild, asymptomatic hypocalcemia of critical illness does not seem to benefit patients and may be associated with longer hospital stays.
C1 Univ Calif San Francisco, J David Gladstone Inst, San Francisco, CA 94141 USA.
   San Francisco VA Med Ctr, Div Endocrinol, San Francisco, CA USA.
RP Chen, HC (reprint author), Univ Calif San Francisco, J David Gladstone Inst, POB 419100, San Francisco, CA 94141 USA.
NR 8
TC 1
Z9 1
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 SEP-OCT
PY 2001
VL 11
IS 5
BP 364
EP 367
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 485CL
UT WOS:000171735900005
ER

PT J
AU Klibanski, A
AF Klibanski, A
TI Neuroendocrinology - Preface
SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
LA English
DT Editorial Material
C1 Harvard Univ, Sch Med, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
RP Klibanski, A (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 0889-8529
J9 ENDOCRIN METAB CLIN
JI Endocrinol. Metabol. Clin. North Amer.
PD SEP
PY 2001
VL 30
IS 3
BP XI
EP XII
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 472YW
UT WOS:000171013400001
ER

PT J
AU Hall, JE
   Gill, S
AF Hall, JE
   Gill, S
TI Neuroendocrine aspects of aging in women
SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
LA English
DT Article
ID GONADOTROPIN-RELEASING-HORMONE; FOLLICLE-STIMULATING-HORMONE; FREE
   ALPHA-SUBUNIT; PITUITARY-OVARIAN FUNCTION; LUTEINIZING-HORMONE;
   POSTMENOPAUSAL WOMEN; GENE-EXPRESSION; LH-SECRETION; MENOPAUSAL
   TRANSITION; HYPOTHALAMIC FUNCTION
AB Recent evidence indicates that age-related neuroendocrine changes occur in women that are independent of those caused by the loss of ovarian feedback accompanying menopause. Studies suggest that both hypothalamic and pituitary changes contribute to the decrease in gonadotropin secretion that occurs with aging. The response to estrogen-negative feedback at the hypothalamus is preserved with aging, whereas the response to estrogen-positive feedback may decrease with aging, although this has not been fully investigated in women. The information to be gained from ongoing studies of the effects of aging on the hypothalamic-pituitary axis will not only provide insights into the process of menopause, but will also contribute to our understanding of general mechanisms underlying the age-related deterioration of other neuroendocrine systems.
C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA.
RP Hall, JE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, BHX-5,55 Fruit St, Boston, MA 02114 USA.
FU NCRR NIH HHS [M01 RR01066]; NIA NIH HHS [R01 AG13241, R01 AG013241]
NR 81
TC 19
Z9 20
U1 0
U2 1
PU W B SAUNDERS CO
PI PHILADELPHIA
PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA
   19106-3399 USA
SN 0889-8529
J9 ENDOCRIN METAB CLIN
JI Endocrinol. Metabol. Clin. North Amer.
PD SEP
PY 2001
VL 30
IS 3
BP 631
EP +
DI 10.1016/S0889-8529(05)70205-X
PG 18
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 472YW
UT WOS:000171013400007
PM 11571934
ER

PT J
AU Anawalt, BD
   Merriam, GR
AF Anawalt, BD
   Merriam, GR
TI Neuroendocrine aging in men - Andropause and somatopause
SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
LA English
DT Article
ID BONE-MINERAL DENSITY; GROWTH-FACTOR-I; HORMONE-RELEASING HORMONE;
   CORONARY HEART-DISEASE; AGE-RELATED-CHANGES; HEALTHY OLDER MEN; ELDERLY
   MEN; LUTEINIZING-HORMONE; BODY-COMPOSITION; TESTOSTERONE REPLACEMENT
AB Testosterone and growth hormone (GH) rise markedly at puberty and contribute to maturational changes in body composition and muscle strength. Both tropic hormones plateau in adult life, and then, because of a combination of central and testicular changes, decline progressively with aging, accompanied by loss of muscle and strength and an increase in body fat that resembles partial hypogonadism or GH deficiency. These parallels have led to speculation and then to clinical studies to test whether supplementing testosterone, GH, or the two together could reverse these age-related changes, boost strength and physical function, and prolong the capacity for independent living. Studies conducted so far encourage this possibility, especially for androgens in men with very low testosterone levels, but published reports are too limited to recommend the general clinical use of androgens, GH, or GH secretagogues in most healthy older men.
C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA.
   Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Dept Obstet & Gynecol, Seattle, WA USA.
RP Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Res A-151, Lakewood, WA 98493 USA.
FU NIA NIH HHS [R01-AG10943]; NIMH NIH HHS [R01-MH53575]
NR 96
TC 46
Z9 52
U1 0
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8529
EI 1558-4410
J9 ENDOCRIN METAB CLIN
JI Endocrinol. Metabol. Clin. North Amer.
PD SEP
PY 2001
VL 30
IS 3
BP 647
EP +
DI 10.1016/S0889-8529(05)70206-1
PG 24
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 472YW
UT WOS:000171013400008
PM 11571935
ER

PT J
AU Szot, P
   White, SS
   McCarthy, EB
   Turella, A
   Rejniak, SX
   Schwartzkroin, PA
AF Szot, P
   White, SS
   McCarthy, EB
   Turella, A
   Rejniak, SX
   Schwartzkroin, PA
TI Behavioral and metabolic features of repetitive seizures in immature and
   mature rats
SO EPILEPSY RESEARCH
LA English
DT Article
DE repetitive seizure; immature brain; flurothyl; c-fos; 2-deoxyglucose;
   hippocampus; ventromedial hypothalamus; pediatric epilepsy
ID KAINIC ACID SEIZURES; STATUS EPILEPTICUS; RECURRENT SEIZURES; NEONATAL
   SEIZURES; ACADEMIC-ACHIEVEMENT; BRAIN-DEVELOPMENT; SUSCEPTIBILITY;
   EPILEPSY; CHILDREN; PENTYLENETETRAZOL
AB Seizure incidence varies significantly with age, with seizure susceptibility particularly high during the first few years of life. Of significant concern is what effects do brief, repetitive seizures have on the developing brain. We approached this issue by examining the change in seizure threshold, and related markers of neuronal activity and metabolic activity (c-fos mRNA and 2-deoxyglucose [2DG]), as a function of repetitive seizure episodes in immature and mature rats. Starting on postnatal day 15 (P15) (immature) or P60 (adult) rats were given two flurothyl seizures a day for 5 days (nine or ten seizures). The seizure latency profile. our measure of threshold, in immature versus adult rats across the 5-day testing period was different. In immature rats. threshold for the second seizure on each day was significantly lower than for the first seizure, suggesting that there was little refractoriness after the first seizure of the day. In contrast, the mature animal had a significantly longer threshold latency to the second seizure for the first 3 days of testing. The immature animal was also more likely than the adult to exhibit tonic extension as a feature of the first seizure of the day. Following repetitive seizures. more regions of the CNS showed c-fos mRNA expression in the immature animal than adults, suggesting that repetitive seizures in the immature animal activated a greater percentage of the brain. Compared with the effects of a single seizure, repetitive seizures resulted in less 2DG labeling in most regions of the brain (except the hippocampus); in the immature brain this difference was more distinct than in adults. The consequences of repetitive seizures in the immature animal results in distinctly different seizure behavior and neuronal activity pattern (c-fos expression) than that observed in the mature animal. (C) 2001 Published by Elsevier Science B.V.
C1 VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA 98108 USA.
   Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
   Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA.
   Univ Washington, Dept Physiol Biophys, Seattle, WA 98195 USA.
RP Szot, P (reprint author), VA Puget Sound Hlth Care Syst, GRECC, 182B,1660 S Columbian Way, Seattle, WA 98108 USA.
FU NINDS NIH HHS [NS-18895]
NR 48
TC 8
Z9 8
U1 2
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-1211
J9 EPILEPSY RES
JI Epilepsy Res.
PD SEP
PY 2001
VL 46
IS 3
BP 191
EP 203
DI 10.1016/S0920-1211(01)00285-6
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA 470QN
UT WOS:000170882800001
PM 11518622
ER

PT J
AU Messas, E
   Chow, CCM
   Sagie, A
   Rudski, L
   Gilon, D
   Levine, R
AF Messas, E
   Chow, CCM
   Sagie, A
   Rudski, L
   Gilon, D
   Levine, R
TI A new noninvasive bedside haemodynamic index of early prognosis after
   acute myocardial infarction
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 Hop Europeen Georges Pompidou, Paris, France.
   Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA USA.
NR 0
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 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD SEP
PY 2001
VL 22
SU S
BP 71
EP 71
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 472MQ
UT WOS:000170988300270
ER

PT J
AU Carroll, DL
   Hamilton, GA
AF Carroll, DL
   Hamilton, GA
TI Health status and quality of life at initial treatment in two cohorts of
   survivors of life-threatening arrhythmias
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Patient Care Serv, Boston, MA USA.
   Univ Oslo, Oslo, Norway.
NR 0
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 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD SEP
PY 2001
VL 22
SU S
BP 212
EP 212
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 472MQ
UT WOS:000170988300822
ER

PT J
AU Ammer, R
   Keane, D
   Aretz, T
   Ruskin, JN
AF Ammer, R
   Keane, D
   Aretz, T
   Ruskin, JN
TI Persistent atrial fibrillation in goats induces apoptosis in atrial
   myocytes and Bcl-2 upregulation in ventricular myocytes
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 German Heart Ctr, Dept Cardiol, D-8000 Munich, Germany.
   Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
NR 0
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 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD SEP
PY 2001
VL 22
SU S
BP 490
EP 490
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 472MQ
UT WOS:000170988301877
ER

PT J
AU Mehta, RH
   Eagle, KA
   Williams, D
   Maroto, LC
   Cooper, J
   Nienaber, CA
   Fattori, R
   Isselbacher, E
AF Mehta, RH
   Eagle, KA
   Williams, D
   Maroto, LC
   Cooper, J
   Nienaber, CA
   Fattori, R
   Isselbacher, E
TI Percutaneous therapeutic procedures in acute aortic dissection: lessons
   from international registry of acute aortic dissection
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 Univ Michigan, Dept Cardiol, Ann Arbor, MI 48109 USA.
   Univ Hosp Eppendorf, Hamburg, Germany.
   Univ Hosp S Orsola, Bologna, Italy.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
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 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD SEP
PY 2001
VL 22
SU S
BP 599
EP 599
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 472MQ
UT WOS:000170988302284
ER

PT J
AU Sinnaeve, P
   Gillijns, H
   Van Pelt, N
   Chiche, JD
   Bloch, K
   Collen, D
   Janssens, S
AF Sinnaeve, P
   Gillijns, H
   Van Pelt, N
   Chiche, JD
   Bloch, K
   Collen, D
   Janssens, S
TI Overexpression of a mutant, cGMP-independent protein kinase reduces
   restenosis in stented porcine coronary arteries
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 Univ Hosp Gasthuisberg, Dept Cardiol, B-3000 Louvain, Belgium.
   Hop Bichat, Dept Anesthesiol, F-75877 Paris, France.
   Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
   Katholieke Univ Leuven, CTG, Louvain, Belgium.
NR 0
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 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD SEP
PY 2001
VL 22
SU S
BP 626
EP 626
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 472MQ
UT WOS:000170988302388
ER

PT J
AU Gerszten, RE
   Friedrich, EB
   Rosenzweig, A
   Force, T
AF Gerszten, RE
   Friedrich, EB
   Rosenzweig, A
   Force, T
TI Activation of PI 3-kinase is sufficient to induce adhesion of monocytes
   under laminar flow conditions
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Charlestown, MA USA.
   Massachusetts Gen Hosp, CIID, Charlestown, MA USA.
   Tufts Univ, Mol Cardiol Res Inst, Boston, MA 02111 USA.
NR 0
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 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD SEP
PY 2001
VL 22
SU S
BP 643
EP 643
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 472MQ
UT WOS:000170988302457
ER

PT J
AU Giugliano, RP
   Llevadot, J
   Wilcox, RG
   Gurfinkel, EP
   McCabe, CH
   Charlesworth, A
   Thompson, SL
   Antman, EM
   Braunwald, E
AF Giugliano, RP
   Llevadot, J
   Wilcox, RG
   Gurfinkel, EP
   McCabe, CH
   Charlesworth, A
   Thompson, SL
   Antman, EM
   Braunwald, E
CA InTIME II Investigators
TI Geographic variation in patient and hospital characteristics,
   management, and clinical outcomes in ST-elevation myocardial infarction
   treated with fibrinolysis - Results from InTIME-II
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE myocardial infarction; fibrinolysis; geographic variation; management;
   outcomes
ID ACUTE CORONARY SYNDROMES; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION
   TASK-FORCE; UNITED-STATES; CARDIAC PROCEDURES; UNSTABLE ANGINA;
   INTERREGIONAL DIFFERENCES; ACC/AHA GUIDELINES; BETA-BLOCKADE; TRIAL
AB Aims We examined the geographic variations in InTIME-II, a randomized double-blind trial comparing alteplase with lanoteplase for myocardial infarction.
   Methods and Results We compared baseline characteristics management, and outcomes in four re.-ions (Western Europe, Eastern Europe, North America, and Latin America) and in countries with historically different management approaches (Germany vs the U.K., the U.S. vs Canada). Thirty-day mortality in Western Europe, Eastern Europe, North America and Latin America was 6.7%, 7.3%, 5.7%, 10.1%, P<0.0001. Adjusted mortality for Europe was intermediate between North America and Latin America (odds ratios (OR) [95% confidence intervals (CI)] compared to Western Europe: North America 0.84 [0.67-1.0], Eastern Europe 1.2 [1.0-1.4], and Latin America 1.8 [1.3-2.7]). Revascularization rates varied 10-fold but did not explain regional mortality differences. Germany and the U.K. had similar adjusted 1-year mortality (OR for the U.K. 1.16 [0.92-1.5]), although invasive procedures were four- to 10-fold more common in Germany. Similarly the U.S. and Canada had equal adjusted 1-year mortality (OR for Canada 0.85 [0.61-1.17]) despite three-fold higher use of invasive procedures in the U.S.
   Conclusions Significant geographic variations in practice and adjusted mortality following fibrinolysis persist despite recent guidelines. These findings have important implications in the design and interpretation of international studies, identify under- and over-utilized therapies, and support further study of treatments with marked worldwide variations.
C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Queens Med Ctr, Div Cardiovasc Med, Nottingham NG7 2UH, England.
   Fdn Favaloro, Buenos Aires, DF, Argentina.
   Nottingham Clin Res Grp, Nottingham, England.
RP Giugliano, RP (reprint author), TIMI Study Off, 333 Longwood Ave,Suite 402, Boston, MA 02115 USA.
NR 31
TC 42
Z9 43
U1 0
U2 0
PU W B SAUNDERS CO LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD SEP
PY 2001
VL 22
IS 18
BP 1702
EP 1715
DI 10.1053/euhj.2001.2583
PG 14
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 472JH
UT WOS:000170980200009
PM 11511120
ER

PT J
AU Fuchs, KP
   Bommer, G
   Dumont, E
   Christoph, B
   Vidal, M
   Kremmer, E
   Kempkes, B
AF Fuchs, KP
   Bommer, G
   Dumont, E
   Christoph, B
   Vidal, M
   Kremmer, E
   Kempkes, B
TI Mutational analysis of the J recombination signal sequence binding
   protein (RBP-J)/Epstein-Barr virus nuclear antigen 2 (EBNA2) and
   RBP-J/Notch interaction
SO EUROPEAN JOURNAL OF BIOCHEMISTRY
LA English
DT Article
DE protein-protein interaction; EBNA2; Notch; RBP-J; reverse yeast
   two-hybrid
ID EPSTEIN-BARR-VIRUS; J-KAPPA; TRANSCRIPTION FACTOR; REVERSE 2-HYBRID;
   DOMAIN; DNA; NOTCH; RECEPTOR; PROMOTER; CBF1
AB Epstein-Barr virus nuclear antigen 2 (EBNA2) and the Notch protein both function within the nucleus as transcriptional adaptor proteins. EBNA2 plays a key role during the immortalization of primary B-cells by Epstein-Barr virus (EBV). Notch proteins are involved in lymphomagenesis as well as in multiple cell fate decisions during tissue differentiation and development. Both, EBNA2 and Notch interact with the DNA binding protein RBP-J and thereby gain access to the promoter of their target genes. In order to identify regions within the J recombination signal sequence binding protein (RBP-J), that are relevant for either the Notch or the EBNA2 interaction, we have performed a mutational analysis of RBP-J. A library of RBP-J mutants was screened by a reverse two-hybrid system for alleles that fail to bind to either EBNA2 or Notch. The sequence analysis of these alleles reveals that a limited and particularly distinct number of amino-acid positions are relevant for either interaction only. Given the important role of RBP-J in B-cell immortalization, the EBNA2/RBP-J protein-protein interaction could be a candidate target for therapeutic intervention in EBV related diseases.
C1 GSF Forschungszentrum Umwelt & Gesundheit, Inst Klin Mol Biol & Tumorgenet, D-81377 Munich, Germany.
   GSF Forschungszentrum Umwelt & Gesundheit, Munich, Germany.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
RP Kempkes, B (reprint author), GSF Forschungszentrum Umwelt & Gesundheit, Inst Klin Mol Biol & Tumorgenet, Marchioninistr 25, D-81377 Munich, Germany.
RI Kempkes, Bettina/B-3322-2013; 
OI Bommer, Guido/0000-0001-6898-4884
NR 40
TC 16
Z9 17
U1 0
U2 1
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 SEP
PY 2001
VL 268
IS 17
BP 4639
EP 4646
DI 10.1046/j.1432-1327.2001.02387.x
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 470ZZ
UT WOS:000170903500005
PM 11532000
ER

PT J
AU Marshall, D
   Simpson, KN
   Earle, CC
   Chu, CW
AF Marshall, D
   Simpson, KN
   Earle, CC
   Chu, CW
TI Economic decision analysis model of screening for lung cancer
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE lung cancer screening; cost-effectiveness; decision analysis; helical
   computed tomography
ID COST-EFFECTIVENESS; SURVIVAL; PROSTATE; PROJECT; STAGE; VIEW; AGE
AB The objective of this study was to evaluate the potential clinical and economic implications of an annual lung cancer screening programme based on helical computed tomography (CT), A decision analysis model was created using combined data from the Surveillance, Epidemiology and End Results (SEER) registry public-use database and published results from the Early Lung Cancer Action Project (ELCAP). We found that under optimal conditions in a high risk cohort of patients between 60 and 74 years of age, annual I-Ling cancer screening over a period of 5 years appears to be cost effective at approximately $19 000 per life year saved. A sensitivity analysis of the model to account for a 1-year decrease in survival benefit and changes in assumptions for incidence rate and costs generated cost effectiveness estimates ranging from approximately $10 800 to $62 000 per life year saved. Based on the assumptions embedded in this model, annual screening of high risk elderly patients for lung cancer may be cost effective under optimal conditions, but longer term data are needed to confirm if this will be borne out in practice. (C) 2001 Elsevier Science Ltd. All rights reserved.
C1 McMaster Univ, St Josephs Hosp, Ctr Evaluat Med, Hamilton, ON L8N 1G6, Canada.
   Med Univ S Carolina, Charleston, SC 29425 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Bayer Diagnost, Emeryville, CA USA.
RP Marshall, D (reprint author), McMaster Univ, St Josephs Hosp, Ctr Evaluat Med, 105 Main St E,Level P1, Hamilton, ON L8N 1G6, Canada.
RI Marshall, Deborah/J-7248-2015
OI Marshall, Deborah/0000-0002-8467-8008
NR 32
TC 60
Z9 60
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0959-8049
J9 EUR J CANCER
JI Eur. J. Cancer
PD SEP
PY 2001
VL 37
IS 14
SI SI
BP 1759
EP 1767
DI 10.1016/S0959-8049(01)00205-2
PG 9
WC Oncology
SC Oncology
GA 470BV
UT WOS:000170851300005
PM 11549429
ER

PT J
AU Correia-Neves, M
   Mathis, D
   Benoist, C
AF Correia-Neves, M
   Mathis, D
   Benoist, C
TI A molecular chart of thymocyte positive selection
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE T cell differentiation; TCR; T cell repertoire; TCR transgenic mice;
   recombination
ID T-CELL-RECEPTOR; CD4/CD8 LINEAGE COMMITMENT; CD8 LINEAGE; CD4+8+
   THYMOCYTES; TRANSGENIC MICE; EXPRESSION; DIFFERENTIATION; MODEL;
   MATURATION; THYMUS
AB As a new slant on T lymphocyte repertoire selection, we have examined batteries of TCR sequences in thymi from transgenic, mice engineered to exhibit limited, focussed TCR diversity. We have tracked the fate of differentiating thymocytes expressing a set of particular TCR through the positive selection process. Subtly different TCR sequences can promote different maturation pathways and commitment choices. Two distinct routes are followed by CD8-lineage cells interacting with MHC class I molecules, via TCRhi CD4(+)CD8(+) or CD4(+)CD8(int) intermediates, while CD4-lineage cells mature exclusively via a CD4(+)CD8(int) stage. The CD8-lineage routes are partially exclusive, indicating that the latter cell type is not always preceded by the former. The distribution of sequences also indicates that CD4/CD8-lineage commitment is not strictly correlated with the class of MHC molecule engaged, and that some mechanism prevents mismatched intermediates from achieving full maturity.
C1 ULP, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, CU Strasbourg, France.
RP Mathis, D (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA.
RI Correia-Neves, Margarida/C-9122-2009
OI Correia-Neves, Margarida/0000-0002-2202-5431
NR 32
TC 17
Z9 18
U1 0
U2 0
PU WILEY-V C H VERLAG GMBH
PI BERLIN
PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD SEP
PY 2001
VL 31
IS 9
BP 2583
EP 2592
DI 10.1002/1521-4141(200109)31:9<2583::AID-IMMU2583>3.0.CO;2-Z
PG 10
WC Immunology
SC Immunology
GA 474EH
UT WOS:000171092400007
PM 11536156
ER

PT J
AU Moody, AM
   Xiong, Y
   Chang, HC
   Reinherz, EL
AF Moody, AM
   Xiong, Y
   Chang, HC
   Reinherz, EL
TI The CD8 alpha beta co-receptor on double-positive thymocytes binds with
   differing affinities to the products of distinct class I MHC loci
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE thymic selection; H-2K(b); H-2D(b); cell fate; MHCl alpha 3 domain
   chimera
ID T-CELL RECEPTOR; CYTOTOXIC LYMPHOCYTES-T; CD8 CORECEPTOR FUNCTION;
   ALPHA-3 DOMAIN; CRYSTAL-STRUCTURE; SELECTION; COMPLEX; EXPRESSION;
   MOLECULES; MICE
AB The CD8 co-receptor is essential for TCR-dependent immune recognition and T cell development involving peptides bound to MHC class I (MHCI) molecules. The dominant interaction of CD8 alpha alpha and alpha beta co-receptors is with the alpha3 domain of an MHCI molecule. Whether this interaction is different for the products of various MHCI loci is currently unknown. Here we examine the interaction between H-2K(b) and H-2D(b), the two MHCI molecules in the C57BL/6 mouse, and CD8 using H-2K(b) and H-2D(b) tetramers. The MHCI molecules bind to the CD8 alpha beta co-receptor on double-positive thymocytes with different avidities (H-2K(b)>D-b). The differences are linked to their respective alpha3 domains. Hence, an H-2D(b)K(b) tetramer comprising D(b)alpha1-alpha2 and K(b)alpha3 domains shows more binding than H-2D(b). We also quantitated the monomeric affinities of CD8 alpha alpha and CD8 alpha beta for H-2K(b) and H-2D(b). The H-2K(b) interaction with CD8 alpha alpha and CD8 alpha beta is stronger than that of H-2D(b). Given that T cell repertoire selection of DP thymocytes is a function of both TCR-pMHCI and CD8 alpha beta -pMHCI avidities, these differences may explain the dominant role of H-2K(b) as compared to H-2D(b) in CD8 T cell development of C57BL/6 mice. The influence of allelic, and non-allelic alpha3 polymorphisms. on thymic selection processes are discussed.
C1 Dana Farber Canc Inst, Immunobiol Lab, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA.
FU NIAID NIH HHS [AI45789, AI45022]
NR 29
TC 30
Z9 30
U1 0
U2 2
PU WILEY-V C H VERLAG GMBH
PI BERLIN
PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY
SN 0014-2980
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD SEP
PY 2001
VL 31
IS 9
BP 2791
EP 2799
DI 10.1002/1521-4141(200109)31:9<2791::AID-IMMU2791>3.0.CO;2-X
PG 9
WC Immunology
SC Immunology
GA 474EH
UT WOS:000171092400029
PM 11536178
ER

PT J
AU Kojika, S
   Griffin, JD
AF Kojika, S
   Griffin, JD
TI Notch receptors and hematopoiesis
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Review
ID DROSOPHILA-MELANOGASTER SUPPRESSOR; T-CELL LEUKEMIA; SIGNALING PATHWAY;
   TRANSCRIPTIONAL REPRESSION; KAPPA-B; NEURONAL DIFFERENTIATION;
   CAENORHABDITIS-ELEGANS; NUCLEAR TRANSLOCATION; PROGENITOR CELLS; ANKYRIN
   REPEATS
AB Notch receptors are involved in a variety of cell-fate decisions that affect the development and function of many organs, including hematopoiesis and the immune system. There are four mammalian Notch receptors that have only partially overlapping functions despite sharing similar structures and ligands. The ligands for Notch are transmembrane proteins expressed on adjacent cells, including Jagged and Delta, and it is quite possible that signaling is bidirectional. A large Notch precursor protein is proteolytically cleaved to form the mature cell-surface receptor. Ligand binding induces additional proteolytic events followed by translocation of the intracellular domain to the nucleus. There, Notch interacts with transcription factors such as RBPJ kappa, activating transcription of basic helix-loop-helix genes such as HES1. These in turn regulate expression of tissue-specific transcription factors that influence lineage commitment and other events. In this review, the details of Notch signaling will be discussed, with a focus on what is known about the role of Notch in hematopoiesis. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med,Dept Adult Oncol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA.
NR 151
TC 88
Z9 97
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD SEP
PY 2001
VL 29
IS 9
BP 1041
EP 1052
DI 10.1016/S0301-472X(01)00676-2
PG 12
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 468WY
UT WOS:000170782200002
PM 11532344
ER

PT J
AU Alcantara, O
   Kalidas, M
   Baltathakis, I
   Boldt, DH
AF Alcantara, O
   Kalidas, M
   Baltathakis, I
   Boldt, DH
TI Expression of multiple genes regulating cell cycle and apoptosis in
   differentiating hematopoietic cells is dependent on iron
SO EXPERIMENTAL HEMATOLOGY
LA English
DT Article
ID NITRIC-OXIDE SYNTHASE; T-CELLS; KINASE; PROGRESSION; TRANSFERRIN;
   LYMPHOCYTES; METABOLISM; INDUCTION; ACID; P53
AB Objective. Iron plays critical roles in many biological processes including hematopoietic cell growth and differentiation. Iron is essential for the differentiation of HL-60 promonocytes. HL-60 cells stimulated with phorbol myristate acetate (PMA) undergo G1/S phase cell-cycle arrest and differentiate to monocyte/macrophages. With iron deprivation, PMA-induced HL-60 cells bypass differentiation and undergo apoptosis. To investigate the molecular basis underlying this observation, we used commercially available gene microarrays to evaluate expression of multiple genes involved in the regulation of cell cycling and apoptosis.
   Methods. We treated HL-60 cells with PMA +/- desferrioxamine (DF), a potent iron chelator, to produce iron deprivation. Cells were cultured for 48 hours, and cDNA was prepared and radiolabeled with alpha-P-32 dCTP, then hybridized to gene arrays containing specific cDNA fragments.
   Results. Expression of 11 of 43 genes was inhibited greater than 50% by iron deprivation. These genes were Rb; p2l (WAF1/CIP1); bad; cdk2; cyclins A, D3, El; c-myc; egr-1; iNOS; and FasL. For each gene the microarray results were confirmed by RT-PCR and/or Northern or Western blotting. Nuclear transcription assays indicated that the role of iron in Rb expression was to support gene transcription. Addition of ferrioxamine (iron saturated DF) instead of DF to PMA-induced cells did not affect gene expression, indicating that diminished expression was due to iron deprivation, not nonspecific toxicity.
   Conclusion. Iron supports expression of multiple cell cycle-regulatory and apoptosis-related genes during HL-60 cell differentiation, and, in this way, is involved in regulation of a critical cell decision point-the decision to pursue a differentiation-related or apoptotic pathway. (C) 2001 International Society for Experimental Hematology. Published by Elsevier Science Inc.
C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA.
   S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA.
RP Boldt, DH (reprint author), Univ Texas, Hlth Sci Ctr, Mail Code 7880,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
FU NIDDK NIH HHS [R01 DK5042]
NR 27
TC 37
Z9 43
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 0301-472X
J9 EXP HEMATOL
JI Exp. Hematol.
PD SEP
PY 2001
VL 29
IS 9
BP 1060
EP 1069
DI 10.1016/S0301-472X(01)00683-X
PG 10
WC Hematology; Medicine, Research & Experimental
SC Hematology; Research & Experimental Medicine
GA 468WY
UT WOS:000170782200004
PM 11532346
ER

PT J
AU Melby, PC
   Tabares, A
   Restrepo, BI
   Cardona, AE
   McGuff, HS
   Teale, JM
AF Melby, PC
   Tabares, A
   Restrepo, BI
   Cardona, AE
   McGuff, HS
   Teale, JM
TI Leishmania donovani: Evolution and architecture of the splenic cellular
   immune response related to control of infection
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE protozoa; Leishmania donovani; T cells; cytokines
ID EXPERIMENTAL VISCERAL LEISHMANIASIS; TRANSFORMING GROWTH FACTOR-BETA-1;
   DENDRITIC CELLS; IFN-GAMMA; CUTANEOUS LEISHMANIASIS; MURINE
   LEISHMANIASIS; INTERFERON-GAMMA; LANGERHANS CELLS; PRODUCE IL-12; TH1
   CELLS
AB Infection with the protozoan Leishmania donovani in humans is usually subclinical. Parasites probably persist for the life of the host and the low-level infection is controlled by the cellular immune response. To better understand the mechanisms related to the control of infection, we studied the evolution and architecture of the splenic cellular immune response in a murine model that is most representative of human subclinical infection. Following systemic inoculation with L. donovani, the parasites were primarily localized to the macrophage-rich splenic red pulp. There was art initial increase in the numbers of T cells and dendritic cells in the periarteriolar lymphoid sheath and marginal zone, but the red pulp (where parasitized macrophages were prominent) remained free of these cells until later in the course of infection. Thus, T cells did not colocalize with parasitized red pulp macrophages until later in the course of infection. Early in the course of infection, IL-10 production within the marginal zone and TGF-beta production by cells in the red pulp were prominent. These macrophage-inhibitory cytokines may contribute to the establishment of the infection and early parasite replication. By day 28 of infection, when the visceral parasite burden began to decline, the number of IL-10-producing spleen cells was back to the baseline level, but IFN-gamma production was higher and the number of IL-12-producing cells was increased dramatically. At this time T cells and dendritic cells had moved out of the lymphoid follicle and marginal zone into the red pulp where the parasites were located. These findings therefore suggest that control of infection is associated with IFN-gamma and IL-12 production and migration of T cells and dendritic cells to the site of chronic parasitism. (C) 2001 Academic Press.
C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA.
   Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78229 USA.
   Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA.
   S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Med Serv, San Antonio, TX 78229 USA.
RP Melby, PC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA.
RI Cardona, Astrid/K-4749-2013
OI Cardona, Astrid/0000-0002-5093-8078
NR 43
TC 33
Z9 33
U1 0
U2 1
PU ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
J9 EXP PARASITOL
JI Exp. Parasitol.
PD SEP
PY 2001
VL 99
IS 1
BP 17
EP 25
DI 10.1006/expr.2001.4640
PG 9
WC Parasitology
SC Parasitology
GA 497JW
UT WOS:000172452600003
PM 11708830
ER

PT J
AU Gorin, Y
   Kim, NH
   Feliers, D
   Bhandari, B
   Choudhury, GG
   Abboud, HE
AF Gorin, Y
   Kim, NH
   Feliers, D
   Bhandari, B
   Choudhury, GG
   Abboud, HE
TI Angiotensin II activates Akt/protein kinase B by an arachidonic
   acid/redox-dependent pathway and independent of phosphoinositide
   3-kinase
SO FASEB JOURNAL
LA English
DT Article
DE kidney; mesangium; hypertrophy; Akt/PKB; Ang II
ID SMOOTH-MUSCLE CELLS; GLOMERULAR MESANGIAL CELLS; NF-KAPPA-B; CYTOSOLIC
   PHOSPHOLIPASE A(2); GLYCOGEN-SYNTHASE KINASE-3; TUBULAR
   EPITHELIAL-CELLS; PROTEIN-KINASE; NADPH OXIDASE; GROWTH-FACTOR;
   ENDOTHELIAL-CELLS
AB Angiotensin II (Ang II) exerts contractile and trophic effects in glomerular mesangial cells (MCs). One potential downstream target of Ang II is the protein kinase Akt/protein kinase B (PKB). We investigated the effect of Ang II on Akt/PKB activity in MCs. Ang II causes rapid activation of Akt/PKB (5-10 min) but delayed activation of phosphoinositide 3-kinase (PI3-K) (30 min). Activation of Akt/PKB by Ang II was not abrogated by the PI3-K inhibitors or by the introduction of a dominant negative PI3-K, indicating that in MCs, PI3-K is not an upstream mediator of Akt/PKB activation by Ang II. Incubation of MCs with phospholipase A(2) Inhibitors also blocked Akt/PKB activation by Ang II. AA mimicked the effect of Ang II. Inhibitors of cyclooxygenase-, lipoxyogenase-, and cytochrome P450-dependent metabolism did not influence AA-induced Akt/PKB activation. However, the antioxidants N-acetylcysteine and diphenylene iodonium inhibited both AA- and Ang II-induced Akt/PKB activation. Dominant negative mutant of Akt/PKB or antioxidants, but not the dominant negative form of PI3-K, inhibited Ang II-induced protein synthesis and cell hypertrophy. These data provide the first evidence that Ang II induces protein synthesis and hypertrophy in MCs through AA/redox-dependent pathway and Akt/PKB activation independent of PI3-K.
C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol MC 7882, San Antonio, TX 78229 USA.
   S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX 78229 USA.
RP Abboud, HE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol MC 7882, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM abboud@uthscsa.edu
FU NIDDK NIH HHS [DK 50190, DK 43988]
NR 51
TC 85
Z9 85
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD SEP
PY 2001
VL 15
IS 11
BP 1909
EP 1920
DI 10.1096/fj..01-0165com
PG 12
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
   Topics; Cell Biology
GA 478XE
UT WOS:000171372700006
PM 11532971
ER

PT J
AU Chen, Z
   Mercedat, N
   Hauser, RB
AF Chen, Z
   Mercedat, N
   Hauser, RB
TI Temporal trend in pH in human semen.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Harvard Univ, Sch Publ Hlth, Boston, MA 02115 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 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2001
VL 76
IS 3
SU 3
MA P398
BP S245
EP S245
DI 10.1016/S0015-0282(01)02726-1
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 470HA
UT WOS:000170863900686
ER

PT J
AU Laufer, MR
   Upton, J
   Schuster, S
   Grier, H
   Emans, S
   Diller, L
AF Laufer, MR
   Upton, J
   Schuster, S
   Grier, H
   Emans, S
   Diller, L
TI Axillary oophoropexy for girls receiving abdominal/pelvic radiation with
   over 20 year follow-up.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 Childrens Hosp, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2001
VL 76
IS 3
SU 3
MA P424
BP S253
EP S254
DI 10.1016/S0015-0282(01)02760-1
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 470HA
UT WOS:000170863900711
ER

PT J
AU McLellan, ST
   Panagoulopoulos, C
   Dickinson, KA
   Wright, DL
   Toth, TL
   Lanzendorf, SE
AF McLellan, ST
   Panagoulopoulos, C
   Dickinson, KA
   Wright, DL
   Toth, TL
   Lanzendorf, SE
TI Effect of incubator air filtration system on IVF outcomes.
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Eastern Virginia Med Sch, Norfolk, VA 23501 USA.
NR 0
TC 3
Z9 3
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2001
VL 76
IS 3
SU 3
MA O271
BP S103
EP S103
DI 10.1016/S0015-0282(01)02303-2
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 470HA
UT WOS:000170863900272
ER

PT J
AU Nakad, TI
   Pru, JK
   Hendry, IR
   Davis, JS
   Rueda, BR
AF Nakad, TI
   Pru, JK
   Hendry, IR
   Davis, JS
   Rueda, BR
TI Fas and ceramide inhibition of the phosphatidylinositol-3-kinase (PI3K)
   cell survival pathway in human granulosa luteal cells (hGLC).
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02115 USA.
   Vet Affairs Med Ctr, Wichita, KS USA.
   Univ Kansas, Sch Med, Womens Res Inst, Wichita, KS 67214 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 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2001
VL 76
IS 3
SU 3
MA P297
BP S209
EP S210
DI 10.1016/S0015-0282(01)02625-5
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 470HA
UT WOS:000170863900585
ER

PT J
AU Wright, DL
   Jones, EL
   Mayer, JF
   Muasher, SJ
   Oehninger, SC
   Lanzendorf, SE
AF Wright, DL
   Jones, EL
   Mayer, JF
   Muasher, SJ
   Oehninger, SC
   Lanzendorf, SE
TI Telomerase activity in biopsied blastomeres of human day three embryos
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
   Eastern Virginia Med Sch, Jones Inst Reprod Med, Norfolk, VA 23501 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 0015-0282
J9 FERTIL STERIL
JI Fertil. Steril.
PD SEP
PY 2001
VL 76
IS 3
SU 3
MA P455
BP S263
EP S264
DI 10.1016/S0015-0282(01)02790-X
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 470HA
UT WOS:000170863900741
ER

PT J
AU Boyko, EJ
   Ahroni, JH
   Stensel, VL
AF Boyko, EJ
   Ahroni, JH
   Stensel, VL
TI Tissue oxygenation and skin blood flow in the diabetic foot: Responses
   to cutaneous warming
SO FOOT & ANKLE INTERNATIONAL
LA English
DT Article
AB We previously reported an unexpected statistically significant decline in the mean transcutaneous partial pressure of oxygen (TcPO2) with cutaneous warming from 37 degreesC to 44 degreesC on the plantar diabetic foot, as opposed to the expected increase seen at the dorsal sites. To elucidate this relationship we compared changes with cutaneous warming in TcPO2 and skin circulation measured by laser Doppler flowmetry on the right plantar foot surface of 20 consecutive subjects.
   Neuropathy by monofilament testing was present in 55% of the cases. Right dorsal foot TcPO2 increased with cutaneous warming from 37 degreesC to 44 degrees by a mean change of +43.6 +/- 20.7 mmHg (+/- standard deviation) in 95% of the cases. In 42% of cases right plantar first metatarsal head TcPO2 fell with warming from 37 degreesC to 44 degreesC by a mean change of -10.7 +/- 7.6 mmHg. In the remaining 58% of cases right plantar first metatarsal head TcPO2 rose by 6.8 +/- 6.3 mmHg. In 95% of cases right plantar great toe laser Doppler perfusion units (LDPU) increased with warming from 36 degreesC to 44 degreesC by a mean change of +50.4 +/- 37.1. Blood flow measured by laser Doppler flowmetry increased in 95% of the subjects with heating.
   The finding that blood flow was increased with warming contradicts the hypothesis that arterioles in the plantar great toe cannot vasodilate in response to thermal stimuli. This finding supports the hypothesis that the decline in TcPO2 with warming might be due to an increase in epidermal oxygen consumption that exceeds the increase in oxygen delivery due to increased blood flow. The pathological mechanisms behind microvascular dysfunction in skin microcirculation in the diabetic foot need further investigation.
C1 Vet Affairs Puget Sound Hlth Care Syst, ERIC, Seattle, WA 98108 USA.
   Univ Washington, Dept Med, Seattle, WA USA.
   Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA.
   Univ Washington, Sch Nursing, Clin Fac, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA.
RP Boyko, EJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, ERIC, S-111-GIMC,1660 S Columbian Way, Seattle, WA 98108 USA.
NR 8
TC 11
Z9 12
U1 0
U2 0
PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC
PI SEATTLE
PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA
SN 1071-1007
J9 FOOT ANKLE INT
JI Foot Ankle Int.
PD SEP
PY 2001
VL 22
IS 9
BP 711
EP 714
PG 4
WC Orthopedics
SC Orthopedics
GA 474EW
UT WOS:000171094200004
PM 11587386
ER

PT J
AU Reid, AE
AF Reid, AE
TI Nonalcoholic steatohepatitis
SO GASTROENTEROLOGY
LA English
DT Review
ID FATTY LIVER-DISEASE; NON-ALCOHOLIC STEATOHEPATITIS; TOTAL
   PARENTERAL-NUTRITION; HEPATIC IRON OVERLOAD; INSULIN-RESISTANCE;
   NATURAL-HISTORY; RAT HEPATOCYTES; MORBID-OBESITY; MESSENGER-RNA;
   RISK-FACTORS
AB Nonalcoholic steatohepatitis (NASH) is a condition characterized by hepatomegaly, elevated serum aminotransferase levels, and a histologic picture similar to alcoholic hepatitis in the absence of alcohol abuse. Most patients with NASH are obese women, and many have diabetes mellitus, hypercholesterolemia, or hypertriglyceridemia. NASH has also been associated with a number of metabolic conditions, surgical procedures, and drug treatments. Most patients are asymptomatic. The most common sign of NASH is hepatomegaly. Stigmata of chronic liver disease are rare. Laboratory abnormalities include a 2-4-fold elevation of serum aminotransferase levels; other liver function test results are usually normal. Histologically, there is moderate to severe macrovesicular steatosis and lobular hepatitis with necrosis or ballooning degeneration and/or fibrosis. The pathogenesis of NASH is poorly understood, but lipid peroxidation and oxidative stress are the leading culprits. The natural history of NASH is unknown, but NASH seems to be a stable disease in most patients. Treatment of NASH is unproven, but weight reduction is recommended in obese patients. Small pilot studies of several drugs have shown promise, but large randomized clinical trials are awaited. Orthotopic liver transplantation is the treatment of choice for end-stage liver disease secondary to NASH.
C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
RP Massachusetts Gen Hosp, Gastrointestinal Unit, GJ 724,55 Fruit St, Boston, MA 02114 USA.
EM areid@partners.org
NR 116
TC 315
Z9 333
U1 5
U2 22
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD SEP
PY 2001
VL 121
IS 3
BP 710
EP 723
DI 10.1053/gast.2001.27126
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 468GY
UT WOS:000170750800025
PM 11522755
ER

PT J
AU Akerkar, GA
   Yee, J
   Hung, R
   McQuaid, K
AF Akerkar, GA
   Yee, J
   Hung, R
   McQuaid, K
TI Patient experience and preferences toward colon cancer screening: a
   comparison of virtual colonoscopy and conventional colonoscopy
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article; Proceedings Paper
CT Digestive Disease Week/101st Annual Meeting of the
   American-Gastroenterological-Association
CY MAY 21-24, 2000
CL SAN DIEGO, CALIFORNIA
SP Amer Gastroenterol Assoc
ID COLORECTAL-CANCER
AB Background. Virtual colonoscopy has excellent sensitivity for the detection of cancer and polyps greater than 1 cm in diameter. For virtual colonoscopy to succeed as a screening test for colorectal neoplasia, it must be well tolerated and accepted by patients. Patients' experiences with virtual colonoscopy and conventional colonoscopy were assessed and compared.
   Methods: Patients referred to the GI clinic for colonoscopy for any indication were recruited to undergo virtual colonoscopy before conventional colonoscopy. Patients were asked to complete a questionnaire twice: after virtual colonoscopy and after completing both tests. Three variables, overall pain, discomfort, and lack of respect, were assessed by using a 7-point Liken scale with higher scores denoting a worse experience. Patients' preferences for virtual colonoscopy versus conventional colonoscopy were determined with a time tradeoff technique. To verify response stability, patients were asked to return an additional questionnaire by mail at 24 hours.
   Results: Two hundred ninety-five patients completed the questionnaire immediately after the procedures, and 83 patients completed the questionnaire at 24 hours. At both 0 and 24 hours, patients reported more pain, discomfort, and less respect after virtual colonoscopy than conventional colonoscopy (p < 0.01). The overall agreement (Kappa statistic) between times 0 and 24 hours was fair. Patients reported that they preferred conventional colonoscopy and would wait longer for conventional colonoscopy (mean = 4.9 weeks) than undergo a virtual colonoscopy (p < 0.01).
   Conclusions: Patients tolerate both virtual colonoscopy and conventional colonoscopy, although they report more pain, discomfort, and less respect undergoing virtual colonoscopy. Efforts to improve patient experience during virtual colonoscopy need to be investigated.
C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Gastroenterol, San Francisco, CA USA.
   Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Radiol, San Francisco, CA USA.
RP Akerkar, GA (reprint author), 3 Alumni Dr, Exeter, NH 03833 USA.
NR 12
TC 87
Z9 90
U1 0
U2 1
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 SEP
PY 2001
VL 54
IS 3
BP 310
EP 315
DI 10.1067/mge.2001.117595
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 468XZ
UT WOS:000170784600006
PM 11522970
ER

PT J
AU Rost, KM
   Duan, NH
   Rubenstein, LV
   Ford, DE
   Sherbourne, CD
   Meredith, LS
   Wells, KB
AF Rost, KM
   Duan, NH
   Rubenstein, LV
   Ford, DE
   Sherbourne, CD
   Meredith, LS
   Wells, KB
CA Quality Improvement Depression Con
TI The Quality Improvement for Depression Collaboration: general analytic
   strategies for a coordinated study of quality improvement in depression
   care
SO GENERAL HOSPITAL PSYCHIATRY
LA English
DT Article
DE depression; quality improvement; primary care; meta-analysis
ID RANDOMIZED CONTROLLED TRIAL; MAJOR DEPRESSION; MEDICAL OUTCOMES;
   METAANALYSIS; MANAGEMENT; INTERVENTION; GUIDELINES; PHYSICIANS;
   EDUCATION; SYMPTOMS
AB It is difficult to evaluate the promise of primary care quality-improvement interventions for depression because published studies have evaluated diverse interventions by using different research designs in dissimilar populations. Preplanned meta-analysis provides an alternative to derive more precise and generalizable estimates of intervention effects; however, this approach requires the resolution of analytic challenges resulting from design differences that threaten internal and external validity. This paper describes the four-project Quality Improvement for Depression (QID) collaboration specifically designed for preplanned meta-analysis of intervention effects on outcomes. This paper summarizes the interventions the four projects tested, characterizes commonalities and heterogeneity in the research designs used to evaluate these interventions, and discusses the implications of this heterogeneity for preplanned meta-analysis. (C) 2001 Elsevier Science Inc. All rights reserved.
C1 Univ Colorado, Hlth Sci Ctr, Dept Family Med, Denver, CO 80220 USA.
   Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA.
   Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA.
   Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA.
   VA Greater Los Angeles Healthcare Syst, Dept Med, Sepulveda, CA 91343 USA.
   RAND Corp, Hlth Program, Santa Monica, CA 90407 USA.
   Johns Hopkins Univ, Sch Med, Dept Gen Internal Med, Baltimore, MD 21205 USA.
RP Rost, KM (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Family Med, 1800 Clermont St,Campus Box B155, Denver, CO 80220 USA.
FU AHRQ HHS [HS08349]; NIMH NIH HHS [MH54443, MH54623, MH54444, MH63651,
   MH50732]
NR 53
TC 50
Z9 51
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 0163-8343
J9 GEN HOSP PSYCHIAT
JI Gen. Hosp. Psych.
PD SEP-OCT
PY 2001
VL 23
IS 5
BP 239
EP 253
DI 10.1016/S0163-8343(01)00157-8
PG 15
WC Psychiatry
SC Psychiatry
GA 483CL
UT WOS:000171616100001
PM 11600165
ER

PT J
AU Hua, J
   Grisafi, P
   Cheng, SH
   Fink, GR
AF Hua, J
   Grisafi, P
   Cheng, SH
   Fink, GR
TI Plant growth homeostasis is controlled by the Arabidopsis BON1 and BAP1
   genes
SO GENES & DEVELOPMENT
LA English
DT Article
DE homeostasis; bonzai1; copine; BAP1; temperature; size
ID PLASMA-MEMBRANE; FREEZING TOLERANCE; COLD-ACCLIMATION; N-COPINE;
   TRANSFORMATION; EXPRESSION; THALIANA; PROTEINS; DOMAIN; YEAST
AB Wild-type Arabidopsis plants maintain a relatively constant size over a wide range of temperatures. Here we show that this homeostasis requires the BONZAI1 (BON1) gene because bon1 null mutants make miniature fertile plants at 22 degreesC but have wild-type appearance at 28 degreesC. The expression of BON1 and a BON1-associated protein (BAP1) is modulated by temperature. Thus BON1 and BAP1 may have a direct role in regulating cell expansion and cell division at lower temperatures. BON1 contains a Ca2+-dependent phospholipid-binding domain and is associated with the plasma membrane. It belongs to the copine gene family, which is conserved from protozoa to humans. Our data suggest that this gene family may function in the pathway of membrane trafficking in response to external conditions.
C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA.
   MIT, Dept Biol, Cambridge, MA 02142 USA.
RP Fink, GR (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
NR 30
TC 86
Z9 95
U1 4
U2 14
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 SEP 1
PY 2001
VL 15
IS 17
BP 2263
EP 2272
DI 10.1101/gad.918101
PG 10
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA 470GT
UT WOS:000170863100009
PM 11544183
ER

PT J
AU de Faria, JML
   Katsumi, O
   Cagliero, E
   Nathan, D
   Hirose, T
AF de Faria, JML
   Katsumi, O
   Cagliero, E
   Nathan, D
   Hirose, T
TI Neurovisual abnormalities preceding the retinopathy in patients with
   long-term type 1 diabetes mellitus
SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
LA English
DT Article
ID CONTRAST SENSITIVITY FUNCTION; VISUAL-EVOKED-RESPONSES; OSCILLATORY
   POTENTIALS; OBJECTIVE ASSESSMENT; ELECTRORETINOGRAM; ACUITY; RETINA;
   PATTERN; DYSFUNCTION; INSULIN
AB Background: Changes in the retina caused by diabetes may lead to visual impairment in dim light, even with good visual acuity and visual fields. To evaluate the visual abnormalities preceding the retinopathy in patients with type 1 diabetes mellitus (DM), we applied electrophysiological methods. Methods: The visual evoked responses were recorded with sinusoidally modulated vertical gratings at 10 spatial frequencies presented sequentially on a high-resolution monitor in patients with type 1 DM and in normal volunteers. Similarly, the contrast visual evoked responses of 10 contrast levels were recorded at five spatial frequencies. Both amplitudes at the second harmonic were calculated by discrete Fourier transform. The visual acuity and contrast thresholds were determined objectively. Results: There was dissociation between the Snellen and the estimated visual evoked response acuity measurements in patients with diabetes (r(2)=0.077, P=0.44). The saturation phenomena were observed at lower levels of contrast stimuli than in normal individuals at. 1.0, 2.0, 4.0 and 8.0 cycles per degree (P=0.0001). The contrast sensitivity function was deeply abnormal in all tested patients despite the metabolic control. The values of the area under the curve of the visual evoked response amplitude-contrast level function at five spatial frequencies were smaller in patients with DM than in the control group (P <0.05) at all spatial frequencies tested. Conclusions: Patients with type 1 DM without retinopathy showed significant lower amplitude of the visual evoked responses at all spatial frequencies tested, with the saturation phenomena observed at lower level of contrast stimuli. In addition, there was a dissociation between the sweep visual evoked responses and the Snellen acuity measurements. A significant and nonselective neuronal visual loss involving the visual pathway precedes the ophthalmoscopically detectable retinopathy in patients with type 1 DM.
C1 Harvard Univ, Sch Med,Schepens Retina Associates, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA.
   State Univ Campinas, UNICAMP, Fac Med Sci, Dept Ophthalmol, Sao Paulo, Brazil.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med,Diabet Unit, Boston, MA USA.
RP Hirose, T (reprint author), Harvard Univ, Sch Med,Schepens Retina Associates, Schepens Eye Res Inst, Dept Ophthalmol, 100 Charles River Plaza,2nd Floor, Boston, MA 02114 USA.
RI Lopes de Faria, Jacqueline /B-3851-2013
OI Lopes de Faria, Jacqueline /0000-0002-4783-4665
NR 42
TC 24
Z9 25
U1 0
U2 1
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0721-832X
J9 GRAEF ARCH CLIN EXP
JI Graefes Arch. Clin. Exp. Ophthalmol.
PD SEP
PY 2001
VL 239
IS 9
BP 643
EP 648
PG 6
WC Ophthalmology
SC Ophthalmology
GA 480UQ
UT WOS:000171481500002
ER

PT J
AU Dore, MP
   Graham, DY
   Mele, R
   Marras, L
   Nieddu, S
   Pisanu, G
   Manca, A
   Realdi, G
AF Dore, MP
   Graham, DY
   Mele, R
   Marras, L
   Nieddu, S
   Pisanu, G
   Manca, A
   Realdi, G
TI Twice day quadruple therapy for Helicobacter pylori infection as primary
   or salvage therapy in a population with a high antibiotic-resistance
   background
SO GUT
LA English
DT Meeting Abstract
C1 Univ Sassari, Inst Internal Med, I-07100 Sassari, Italy.
   Univ Sassari, Inst Histopathol, I-07100 Sassari, Italy.
   VA Med Ctr, Houston, TX USA.
   Baylor Coll Med, Houston, TX 77030 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
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 SEP
PY 2001
VL 49
SU 2
MA 1544
BP A93
EP A94
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476NB
UT WOS:000171232500331
ER

PT J
AU Dore, MP
   Sepulveda, AR
   Cherchi, G
   Marras, L
   Bacciu, PP
   Piccolo, D
   Manca, M
   Graham, DY
   Realdi, G
AF Dore, MP
   Sepulveda, AR
   Cherchi, G
   Marras, L
   Bacciu, PP
   Piccolo, D
   Manca, M
   Graham, DY
   Realdi, G
TI Helicobacter pylori DNA is not detected in atherosclerotic plaques of
   dyspeptic patients
SO GUT
LA English
DT Meeting Abstract
C1 Univ Sassari, Inst Internal Med, I-07100 Sassari, Italy.
   Dept Pathol, Pittsburgh, PA USA.
   Osped SS Annunziata, Lab Pluridisciplinare, Sassari, Italy.
   Univ Sassari, Dept Vasc Surg, I-07100 Sassari, Italy.
   Baylor Coll Med, Houston, TX 77030 USA.
   VA Med Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 SEP
PY 2001
VL 49
SU 2
MA 1301
BP A71
EP A71
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476NB
UT WOS:000171232500247
ER

PT J
AU Dore, MP
   Sanna, G
   Cherchi, GP
   Negrini, R
   Marras, S
   Marras, L
   Simula, L
   Graham, DY
   Realdi, G
AF Dore, MP
   Sanna, G
   Cherchi, GP
   Negrini, R
   Marras, S
   Marras, L
   Simula, L
   Graham, DY
   Realdi, G
TI Helicobacter pylori in sheep and sheep-dogs
SO GUT
LA English
DT Meeting Abstract
C1 Univ Sassari, Inst Internal Med, I-07100 Sassari, Italy.
   Zooprophylact Inst, Brescia, Italy.
   Osped SS Annunziata, Lab Pluridisciplinare, Sassari, Italy.
   Spedali Civil Brescia, Brescia, Italy.
   Baylor Coll Med, Houston, TX 77030 USA.
   VA Med Ctr, Houston, TX USA.
NR 0
TC 1
Z9 1
U1 1
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 SEP
PY 2001
VL 49
SU 2
MA 618
BP A35
EP A35
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476NB
UT WOS:000171232500123
ER

PT J
AU El-Zimaity, HMT
   Katsuyama, T
   Ota, H
   Watanabe, H
   Hattori, T
   Graham, DY
AF El-Zimaity, HMT
   Katsuyama, T
   Ota, H
   Watanabe, H
   Hattori, T
   Graham, DY
TI Gastric histology in patients with carcinoma at the gastro-esophageal
   junction
SO GUT
LA English
DT Meeting Abstract
C1 Baylor Coll Med, Houston, TX 77030 USA.
   Shinshu Univ Hosp, Matsumoto, Nagano, Japan.
   Niigata Univ, Niigata, Japan.
   Shiga Univ, Shiga, Japan.
   VA Med Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 SEP
PY 2001
VL 49
SU 2
MA 1119
BP A65
EP A65
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476NB
UT WOS:000171232500233
ER

PT J
AU Graham, DY
   Opekun, AR
   El-Zimaity, HMT
   Qureshi, W
   Peterson, LH
AF Graham, DY
   Opekun, AR
   El-Zimaity, HMT
   Qureshi, W
   Peterson, LH
TI Interactions between Helicobacter pylori and NSAIDs with regard to the
   healing rates of acute gastric ulcers
SO GUT
LA English
DT Meeting Abstract
C1 Baylor Coll Med, Houston, TX 77030 USA.
   VA Med Ctr, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 SEP
PY 2001
VL 49
SU 2
MA 1106
BP A62
EP A62
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476NB
UT WOS:000171232500220
ER

PT J
AU Hanninen, M
   Utriainen, M
   Happonen, I
   Dewhirst, FE
AF Hanninen, M
   Utriainen, M
   Happonen, I
   Dewhirst, FE
TI Helicobacter rappinii a novel Helicobacter species including the type
   strains of Helicobacter species flexispira taxons 1, 4 and 5
SO GUT
LA English
DT Meeting Abstract
C1 Fac Med Vet, Helsinki, Finland.
   Forsyth Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 SEP
PY 2001
VL 49
SU 2
MA 902
BP A51
EP A51
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476NB
UT WOS:000171232500180
ER

PT J
AU Malaty, H
   Sedlackova, M
   Graham, DY
   Marx, D
   Reddy, S
   Volf, V
AF Malaty, H
   Sedlackova, M
   Graham, DY
   Marx, D
   Reddy, S
   Volf, V
TI Helicobacter pylori infection in symptomatic and asymptomatic children
   in the Czech republic
SO GUT
LA English
DT Meeting Abstract
C1 Baylor Coll Med, Houston, TX 77030 USA.
   Charles Univ, Prague, Czech Republic.
   VA Med Ctr, Houston, TX USA.
NR 0
TC 1
Z9 1
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 SEP
PY 2001
VL 49
SU 2
MA 1423
BP A80
EP A80
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476NB
UT WOS:000171232500284
ER

PT J
AU Pena, JA
   McNeil, K
   Fox, JG
   Versalovic, J
AF Pena, JA
   McNeil, K
   Fox, JG
   Versalovic, J
TI Molecular evidence of Helicobacter cinaedi-like organisms in human
   gastric biopsies
SO GUT
LA English
DT Meeting Abstract
C1 Northeastern Univ, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   MIT, Cambridge, MA 02139 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 SEP
PY 2001
VL 49
SU 2
MA 912
BP A53
EP A53
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476NB
UT WOS:000171232500190
ER

PT J
AU Whary, MT
   Shi, H
   White, H
   Nagler-Anderson, C
   Fox, JG
AF Whary, MT
   Shi, H
   White, H
   Nagler-Anderson, C
   Fox, JG
TI Th2 responses to the helminth Heligmosomoides polygyrus reduce
   Th1-promoted epithelial hyperplasia in a mouse model of Helicobacter
   hepaticus-associated inflammatory bowel disease (IBD)
SO GUT
LA English
DT Meeting Abstract
C1 MIT, Cambridge, MA 02139 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 2
U2 2
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 SEP
PY 2001
VL 49
SU 2
MA 901
BP A51
EP A51
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 476NB
UT WOS:000171232500179
ER

PT J
AU Feltmate, CM
   Genest, DR
   Wise, L
   Bernstein, MR
   Goldstein, DP
   Berkowitz, RS
AF Feltmate, CM
   Genest, DR
   Wise, L
   Bernstein, MR
   Goldstein, DP
   Berkowitz, RS
TI Placental site trophoblastic tumor: A 17-year experience at the New
   England Trophoblastic Disease Center
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE placental site trophoblastic tumor; prognostic indicators
ID MR APPEARANCE; CHEMOTHERAPY; PSEUDOTUMOR
AB Objective. We reviewed cases of placental site trophoblastic tumors from the New England Trophoblastic Disease Center (NETDC) database from 1982-1999 in an effort to identify prognostic factors for recurrent disease.
   Methods. A chart review was performed utilizing patients identified from the NETDC database. Data obtained included patient age at diagnosis, antecedent pregnancy, duration and extent of disease, presenting symptoms, pre- and posttreatment hCG levels, diagnostic and therapeutic procedures, treatment and outcome of patients. Statistical analysis was performed using Student's t test and chi (2) test when appropriate.
   Results. Thirteen patients were identified. All ultimately underwent hysterectomy although initial treatment of 1 patient was uterine resection. There were 5 recurrences (43%)-3 among the 9 patients who had no metastases on presentation (33%) and 2 of 3 patients who presented with metastases (66%). The 5 patients who recurred were among 8 who had received peri- or postoperative chemotherapy (62.5%). Treatment of recurrences included continued or alternate chemotherapy, radiotherapy, and/or excision of locally recurrent disease. Follow up time averaged 56.2 months (range 12-182 months). One of the 4 patients receiving chemotherapy less than or equal to1 week after hysterectomy recurred, whereas all 4 patients who received chemotherapy 3 weeks or more after hysterectomy recurred. Uterine tumor volume was significantly greater, 154.1 cm(3), in patients with initial metastases versus 42.3 cm(3) in patients without initial metastases (P = 0.04). Mitotic index (P = 0.04) was significantly increased in patients who developed recurrent disease.
   Conclusion. High mitotic index appears to be an adverse prognostic indicator for recurrence. Hysterectomy remains the mainstay of treatment. Chemotherapy is indicated for patients with metastases and may be indicated when the mitotic index is >5 mitoses/10 HPF. Radiation treatment may play a role in recurrent disease but must be evaluated on a case-by-case basis. (C) 2001 Academic Press.
C1 Harvard Univ, Brigham & Womens Hosp,Div Gynecol Oncol, Sch Med,New England Trophoblast Dis Ctr, Dana Farber Canc Inst,Gillette Ctr Womens Canc, Boston, MA 02115 USA.
   Harvard Univ, Brigham & Womens Hosp,Epidemiol Ctr,Dept Obstet &, Sch Med,New England Trophoblast Dis Ctr, Dana Farber Canc Inst,Gillette Ctr Womens Canc, Boston, MA 02115 USA.
   Harvard Univ, Brigham & Womens Hosp,Dept Pathol, Sch Med,New England Trophoblast Dis Ctr, Dana Farber Canc Inst,Gillette Ctr Womens Canc, Boston, MA 02115 USA.
RP Feltmate, CM (reprint author), Harvard Univ, Brigham & Womens Hosp,Div Gynecol Oncol, Sch Med,New England Trophoblast Dis Ctr, Dana Farber Canc Inst,Gillette Ctr Womens Canc, Boston, MA 02115 USA.
OI Wise, Lauren/0000-0003-2138-3752
NR 12
TC 64
Z9 72
U1 0
U2 1
PU ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD SEP
PY 2001
VL 82
IS 3
BP 415
EP 419
DI 10.1006/gyno.2001.6265
PG 5
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 470UC
UT WOS:000170888700002
PM 11520134
ER

PT J
AU Nogueira, IP
   Biggs, PJ
AF Nogueira, IP
   Biggs, PJ
TI Measurement of scatter factors for 4, 6, 10 and 23 MV X rays at
   scattering angles between 30 degrees and 135 degrees
SO HEALTH PHYSICS
LA English
DT Article
DE shielding; photons; radiation therapy; National Council on Radiation
   Protection and Measurements
ID IONIZATION-CHAMBER; RECOMBINATION; COLLECTION
AB NCRP Report No. 49, published in 1976, describes how to calculate the shielding for the medical use of x rays and gamma rays for energies up to 10 MV, including primary, scattered, and leakage radiation. However, in that report, data for scattered radiation for linear accelerators exist only for 6 MV, and leakage radiation is assumed, incorrectly, to be equivalent to primary radiation. Since the publication of that report, linear accelerators with energies up to 25 MV have been widely used in the radiation therapy community. Thus, there is a need to measure additional data for all energies in the range 4-25 MV. In this study, measurements were made of the "a" factor for 4, 6, 10, and 23 MV x rays at scattering angles between 30 degrees and 135 degrees. The results show that the 6 and 10 MV "a" factor data are consistent with published data, and the 23 MV data are also consistent with recently published data at 18 and 25 MV. The data show that, in general, the "a" factor decreases with energy; the exception is that 23 MV data show a sharp increase at low scattering angles, much greater than at other energies.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Biggs, PJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
EM pjbiggs@partners.org
NR 15
TC 4
Z9 4
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0017-9078
EI 1538-5159
J9 HEALTH PHYS
JI Health Phys.
PD SEP
PY 2001
VL 81
IS 3
BP 330
EP 340
DI 10.1097/00004032-200109000-00014
PG 11
WC Environmental Sciences; Public, Environmental & Occupational Health;
   Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
   Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
   Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
   Medical Imaging
GA 462JT
UT WOS:000170417500014
PM 11513466
ER

PT J
AU Le Doux, JM
   Landazuri, N
   Yarmush, ML
   Morgan, JR
AF Le Doux, JM
   Landazuri, N
   Yarmush, ML
   Morgan, JR
TI Complexation of retrovirus with cationic and anionic polymers increases
   the efficiency of gene transfer
SO HUMAN GENE THERAPY
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; MURINE LEUKEMIA; HIGH-TITER; PROTEOGLYCANS;
   INFECTION; THERAPY; GLYCOSAMINOGLYCANS; PARTICLES; MEMBRANE; VECTORS
AB Previously, we have demonstrated that chondroitin sulfate proteoglycans and glycosaminoglycans inhibit retrovirus transduction. While studying the mechanism of inhibition, we found that the combined addition of equal-weight concentrations (80 mug/ml) of Polybrene and chondroitin sulfate C to retrovirus stocks resulted in the formation of a high-molecular-weight retrovirus-polymer complex that could be pelleted by low-speed centrifugation. The pelleted complex contained more than 80% of the virus particles, but less than 0.3% of the proteins that were originally present in the virus stock. Surprisingly, the virus in the complex remained active and could be used to transduce cells. The titer of the pelleted virus, when resuspended in cell culture medium to the starting volume, was three-fold greater than the original virus stock. The selectivity (CFU/mg protein) of the process with respect to virus activity was more than 1000-fold. When the pelleted virus-polymer complex was resuspended in one-eighth of the original volume and used to transduce NIH 3T3 murine fibroblasts and primary human fibroblasts, gene transfer was increased 10- to 20-fold over the original unconcentrated retrovirus stock. The implications of our findings for the production, processing, and use of retrovirus stocks for human gene therapy protocols are discussed.
C1 Georgia Tech Emory, Dept Biomed Engn, Atlanta, GA 30332 USA.
   Shriners Hosp Children, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA.
RP Morgan, JR (reprint author), Shriners Hosp Children, 51 Blossom St,Room 221, Boston, MA 02114 USA.
OI Morgan, Jeffrey/0000-0002-7546-3443
FU NICHD NIH HHS [HD-28528]
NR 31
TC 60
Z9 62
U1 0
U2 3
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 SEP
PY 2001
VL 12
IS 13
BP 1611
EP 1621
DI 10.1089/10430340152528110
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
   Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
   Experimental Medicine
GA 468PT
UT WOS:000170766400002
PM 11535165
ER

PT J
AU Haataja, R
   Marttila, R
   Uimari, P
   Lofgren, J
   Ramet, M
   Hallman, M
AF Haataja, R
   Marttila, R
   Uimari, P
   Lofgren, J
   Ramet, M
   Hallman, M
TI Respiratory distress syndrome: evaluation of genetic susceptibility and
   protection by transmission disequilibrium test
SO HUMAN GENETICS
LA English
DT Article
ID SURFACTANT PROTEIN-A; LINKAGE DISEQUILIBRIUM; SP-B; ASSOCIATION;
   COLLECTINS; DISEASE; LOCUS
AB Based on epidemiological data and genetic association studies, neonatal respiratory distress syndrome (RDS) is a complex disease with a multigenic background. The genes coding for surfactant proteins (SP) A and B have been assigned as the most likely genes in the etiology of RDS. The major factor predisposing to RDS is prematurity, and thus the phenotype of a very premature newborn infant that does not develop the disease can be regarded as hypernormal. Altogether 107 father-mother-offspring trios were divided into two sets according to the proband's phenotype, to evaluate familial segregation of candidate gene polymorphisms by the transmission disequilibrium test. A set of 76 trios were analyzed for transmission disequilibrium from parents to affected offspring. Another set of 31 trios were studied for allele transmission from parents to hypernormal offspring born very prematurely before the gestational age of 32 weeks. SP-A1-A2 haplotype 6A(2)-1A(0) showed significant excess transmission to affected infants and SP-A1 allele 6A(2) decreased transmission to the hypernormals. The present family study provides strong support for a direct or indirect role of the SP-A alleles as genetic predisposers to RIDS in premature infants. The inclusion of parent-hypernormal offspring trios in transmission disequilibrium test is a useful approach to test for genetic protection against a disease.
C1 Univ Oulu, Dept Pediat, Oulu 90014, Finland.
   Bioctr Oulu, Oulu 90014, Finland.
   Cent Hosp So Ostrobothnia, Seinajoki, Finland.
   CSC Sci Comp Ltd, Espoo, Finland.
   Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Hallman, M (reprint author), Univ Oulu, Dept Pediat, POB 5000, Oulu 90014, Finland.
OI Uimari, Pekka/0000-0002-5349-3932
NR 25
TC 32
Z9 36
U1 0
U2 0
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0340-6717
J9 HUM GENET
JI Hum. Genet.
PD SEP
PY 2001
VL 109
IS 3
BP 351
EP 355
DI 10.1007/s004390100574
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 483UY
UT WOS:000171655300014
PM 11702216
ER

PT J
AU Yunis, JJ
   Yunis, EJ
   Yunis, E
AF Yunis, JJ
   Yunis, EJ
   Yunis, E
TI Genetic relationship of the Guambino, Paez, and Ingano Amerindians of
   southwest Colombia using major histocompatibility complex class II
   haplotypes and blood groups
SO HUMAN IMMUNOLOGY
LA English
DT Article; Proceedings Paper
CT HLA and Anthropology Workshop Conjoint Meeting of the
   Human-Biology-Association/American-Association-of-Physical-Anthropologis
   ts
CY MAR   28, 2001
CL KANSAS CITY, MISSOURI
SP Human Biol Assoc, Amer Assoc Phys Anthropol
DE Amerindians; blood groups; Colombia; HLA; MHC; PCR
ID AMERICAN-INDIAN TRIBE; HLA-B ALLELES; MOLECULAR ANALYSIS; LOWER
   AMAZONIA; POLYMORPHISM; POPULATIONS; SYSTEM; LOCI; EVOLUTION; ANTIGENS
AB We analyzed the Amerindian tribes, Guambiano, Ingano, and Paez of the southwest section of Colombia by major histocompatibility complex class II typing and blood group analysis in order to establish their genetic relationship. In addition, genetic admixture with Caucasian and African ancestry were determined based on blood group typing. The Paez showed admixture with Caucasian populations (22.4%), while the Ingano and Guambiano showed some admixture with Black populations (9.2 and 4.6%, respectively), The Ingano had MHC class II haplotypes found mainly in Amerindian and Asian Populations with no evidence of class II haplotypes of African origin. MHC class II haplotypes of Amerindian and Asian populations and some haplotypes frequently found in European Caucasians and Asians and haplotypes of European Caucasians were found in Guambiano and Paez tribes. We compared our results with those previously reported for four Amerindian tribes on Northern Colombia. The presence of some MHC class II haplotypes in the Guambiano, Paez, and Ingano tribes and their absence in the Chibcha speaking groups of Northern Colombia suggest that these tribes originated, together with other Amerindians, from a separate migration or by genetic drift from an ancestral population. Therefore they are genetically distant from Chibcha speaking tribes of Colombia. Human Immunology 62, 970-978 (2001). (C) American Society for Histocompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.
C1 Univ Nacl Colombia, Fac Med, Inst Genet, Dept Pathol, Bogota, DC, Colombia.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Yunis, JJ (reprint author), Univ Nacl Colombia, Fac Med, Inst Genet, Dept Pathol, Bogota, DC, Colombia.
FU NHLBI NIH HHS [HL-29582, HL-59838]
NR 52
TC 11
Z9 13
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 0198-8859
J9 HUM IMMUNOL
JI Hum. Immunol.
PD SEP
PY 2001
VL 62
IS 9
BP 970
EP 978
DI 10.1016/S0198-8859(01)00295-6
PG 9
WC Immunology
SC Immunology
GA 469UY
UT WOS:000170835500012
PM 11543899
ER

PT J
AU Chae, CU
   Lee, RT
   Rifai, N
   Ridker, PM
AF Chae, CU
   Lee, RT
   Rifai, N
   Ridker, PM
TI Blood pressure and inflammation in apparently healthy men
SO HYPERTENSION
LA English
DT Article
DE blood pressure; cell adhesion molecules; inflammation; interleukins;
   risk factors
ID INTERCELLULAR-ADHESION MOLECULE-1; FUTURE MYOCARDIAL-INFARCTION;
   CARDIOVASCULAR-DISEASE; PLASMA-CONCENTRATION; ENDOTHELIAL-CELLS;
   ANGIOTENSIN-II; HYPERTENSION; INTERLEUKIN-6; EXPRESSION; ATHEROSCLEROSIS
AB Inflammation plays an important role in the development of atherosclerosis, but the specific stimuli governing cytokine release in atherogenesis are unknown. We examined the hypothesis that hypertension may increase the risk of atherosclerosis via proinflammatory effects. In a cross-sectional study involving 508 apparently healthy men, we studied the association between blood pressure and baseline plasma concentrations of 2 inflammatory markers, intercellular adhesion molecule-1 (sICAM-1) and interleukin-6 (IL-6). Increase in systolic blood pressure (SBP) (P=0.003), pulse pressure (PP) (P=0.019), and mean arterial pressure (P=0.014) was significantly associated with levels of sICAM-1. All of these measures of blood pressure, as well as diastolic blood pressure (DBP), were significantly associated with levels of IL-6 (all, P less than or equal to0.001). In multiple linear regression models controlled for age and other cardiac risk factors, SBP (7.6 ng/mL per 10 mm Hg, P=0.016) and PP (8.13 ng/mL per 10 mm Hg, P=0.038) were significantly associated with sICAM-1 levels, whereas SBP (0.11 pg/mL per 10 mm Hg, P<0.001), DBP (0.11 pg/mL per 10 mm Hg, P=0.008), PP (0.10 pg/mL per 10 mm Hg, P=0.009), and mean arterial pressure (0.15 pg/mL per 10 nim Hg, P<0.001) had similar strong relationships with log-transformed IL-6 levels. Therefore, in apparently healthy men, we observed. significant graded relationships between blood pressure and levels of sICAM-1 as well as IL-6. These data suggest that increased blood pressure may be a stimulus for inflammation and that this is a possible mechanism underlying the well-established role of hypertension as a risk factor for atherosclerotic disease.
C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Brigham & Womens Hosp, Leducq Ctr Mol & Genet Epidemiol Cardiovasc Disor, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiol, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Childrens Hosp, Med Ctr, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02215 USA.
RP Chae, CU (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA.
FU NHLBI NIH HHS [HL58755, HL63292, K08 HL 04154-01]
NR 25
TC 375
Z9 412
U1 1
U2 11
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0194-911X
J9 HYPERTENSION
JI Hypertension
PD SEP
PY 2001
VL 38
IS 3
BP 399
EP 403
PG 5
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 476KR
UT WOS:000171226700019
PM 11566912
ER

PT J
AU Mahata, SK
   Mahapatra, NR
   Mahata, M
   Wang, TC
   O'Connor, DT
AF Mahata, SK
   Mahapatra, NR
   Mahata, M
   Wang, TC
   O'Connor, DT
TI Stimulus-transcription coupling during sympathetic outflow in vivo: A
   novel transgenic promoter/photoprotein approach.
SO HYPERTENSION
LA English
DT Meeting Abstract
C1 Univ Calif San Diego, San Diego, CA 92103 USA.
   Massachusetts Gen Hosp, 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 0194-911X
J9 HYPERTENSION
JI Hypertension
PD SEP
PY 2001
VL 38
IS 3
MA P104
BP 508
EP 508
PG 1
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 476KR
UT WOS:000171226700229
ER

PT J
AU Shimada, SD
   Cooper, RA
   Boninger, ML
   Koontz, AM
   Corfman, TA
AF Shimada, SD
   Cooper, RA
   Boninger, ML
   Koontz, AM
   Corfman, TA
TI Comparison of three different models to represent the wrist during
   wheelchair propulsion
SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
LA English
DT Article
DE biomechanics; modeling; wheelchair; wrist
ID CARPAL-TUNNEL SYNDROME; KINEMATICS; MOTION; BIOMECHANICS; INDUSTRY;
   ANGLES
AB Due to the high incidence of secondary wrist injury among manual wheelchair users, recent emphasis has been placed on the investigation of wheelchair propulsion biomechanics. Accurate representation of wrist activity during wheelchair propulsion may help to elucidate the mechanisms contributing to the development of wrist injuries. Unfortunately, no consensual wrist biomechanical model has been established. In order to determine if different methodologies obtain similar results, this investigation created and compared three different wrist models: 1) a fixed joint center placed between the styloids (midstyloid joint center); 2) a joint center with 2 degrees of freedom computed from de Leva's joint center data; and 3) a floating joint center. Results indicate that wrist flexion and extension angles are highly consistent between models, however, radial and ulnar deviation angles vary considerably. Mean maximum right flexion angles were found to be 3.5 degrees, 2.2 degrees, and 5.0 degrees for the midstyloid, de Leva, and floating joint center models, respectively. Extension angles were 22.3 degrees, 23.6 degrees, and 23.6 degrees, respectively. Mean maximum right radial deviation angles for the midstyloid, de Leva, and floating joint center models were 26.0 degrees, 26.9 degrees, and 45.1 degrees, respectively, and ulnar deviation angles were found to be 30.5 degrees, 38.8 degrees, and 10.2 degrees, respectively. This information is useful when comparing kinematic studies and further supports the need for consensual methodology.
C1 Biomech Consulting, Davis, CA 95616 USA.
   Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA.
   Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15261 USA.
   Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA.
   VA Pittsburgh Healthcare Syst, VA Ctr Excellence Wheelchairs & Related Technol, Human Engn Res Labs, Pittsburgh, PA 15206 USA.
RP Shimada, SD (reprint author), Biomech Consulting, Davis, CA 95616 USA.
OI Boninger, Michael/0000-0001-6966-919X
FU NICHD NIH HHS [P01 HD33989-01]
NR 34
TC 9
Z9 9
U1 0
U2 2
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI NEW YORK
PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA
SN 1534-4320
J9 IEEE T NEUR SYS REH
JI IEEE Trans. Neural Syst. Rehabil. Eng.
PD SEP
PY 2001
VL 9
IS 3
BP 274
EP 282
DI 10.1109/7333.948455
PG 9
WC Engineering, Biomedical; Rehabilitation
SC Engineering; Rehabilitation
GA 472CK
UT WOS:000170965500004
PM 11561663
ER

PT J
AU Johnson, JR
   O'Bryan, TT
   Kuskowski, M
   Maslow, JN
AF Johnson, JR
   O'Bryan, TT
   Kuskowski, M
   Maslow, JN
TI Ongoing horizontal and vertical transmission of virulence genes and papA
   alleles among Escherichia coli blood isolates from patients with
   diverse-source bacteremia
SO INFECTION AND IMMUNITY
LA English
DT Article
ID MULTILOCUS ENZYME ELECTROPHORESIS; URINARY-TRACT INFECTIONS;
   PATHOGENICITY ISLAND; NEONATAL MENINGITIS; CLONAL RELATIONSHIPS;
   NATURAL-POPULATIONS; ACUTE CYSTITIS; CLASS-I; STRAINS; SEQUENCES
AB The phylogenetic distributions of multiple putative virulence factors (VFs) and papA (P fimbrial structural subunit) alleles among 182 Escherichia coli blood isolates from patients with diverse-source bacteremia were defined. Phylogenetic correspondence among these strains, the E. coli Reference (ECOR) collection, and other collections of extraintestinal pathogenic E. coli (ExPEC) was assessed. Although among the 182 bacteremia isolates phylogenetic group B2 predominated, exhibited the greatest concentration of individual VFs, and contained the largest number of familiar virulent clones, other phylogenetic groups exhibited greater concentrations of certain VFs than did group B2 and included several additional virulent clones. Certain of the newly detected VF genes, e.g., fyuA (yersiniabactin; 76%) and focG (F1C fimbriae; 25%), were as prevalent or more prevalent than their more familiar traditional counterparts, e.g., iut (aerobactin; 57%) and sfaS (S fimbriae; 14%), thus possibly offering additional useful targets for preventive interventions. Considerable diversity of VF profiles was observed at every level within the phylogenetic tree, including even within individual lineages. This suggested that many different pathways can lead to extraintestinal virulence in E. coli and that the evolution of ExPEC, which involves extensive horizontal transmission of VFs and continuous remodeling of pathogenicity-associated islands, is a highly active, ongoing process.
C1 Minneapolis VA Med Ctr, Med Serv, Minneapolis, MN 55417 USA.
   Minneapolis VA Med Ctr, Geriatr REs Educ & Clin Ctr, Minneapolis, MN 55417 USA.
   Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
   Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
   Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
   Philadelphia VA Med Ctr, Med Serv, Philadelphia, PA USA.
RP Johnson, JR (reprint author), Minneapolis VA Med Ctr, Med Serv, 111F,1 Veterans Dr, Minneapolis, MN 55417 USA.
FU NIDDK NIH HHS [DK-47504]
NR 80
TC 75
Z9 75
U1 1
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 SEP
PY 2001
VL 69
IS 9
BP 5363
EP 5374
DI 10.1128/IAI.69.9.5363-5374.2001
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 464PB
UT WOS:000170540000019
PM 11500406
ER

PT J
AU Matute-Bello, G
   Frevert, CW
   Liles, WC
   Nakamura, M
   Ruzinski, JT
   Ballman, K
   Wong, WA
   Vathanaprida, C
   Martin, TR
AF Matute-Bello, G
   Frevert, CW
   Liles, WC
   Nakamura, M
   Ruzinski, JT
   Ballman, K
   Wong, WA
   Vathanaprida, C
   Martin, TR
TI Fas/Fas ligand system mediates epithelial injury, but not pulmonary host
   defenses, in response to inhaled bacteria
SO INFECTION AND IMMUNITY
LA English
DT Article
ID ACUTE LUNG INJURY; FAS LIGAND; ESCHERICHIA-COLI; APOPTOSIS; CELLS;
   EXPRESSION; RECEPTOR; MICE; ACTIVATION; MECHANISMS
AB The Fas/Fas ligand (FasL) system has been implicated in alveolar epithelial cell apoptosis during pulmonary fibrosis and acute respiratory distress syndrome. However, Fas ligation can also lead to cell activation and cytokine production. The goal of this study was to determine the role of the Fas/FasL system in host defenses against Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae. We administered bacteria by aerosolization into the lungs of Fas-deficient (lpr) mice and wild-type (C57BL/6) mice and measured bacterial clearance at 6 and 12 h. One hour prior to euthanasia, the mice received an intraperitoneal injection of human serum albumin (HSA) for alveolar permeability determinations. At all times after bacterial challenges, the lungs of the lpr mice contained similar or lower numbers of bacteria than those of the C57BL/6 mice. Alveolar permeability changes, as determined by bronchoalveolar lavage fluid HSA concentrations, were less severe in the lpr mice 6 h after the challenges. In response to E. coli, the lpr mice had significantly more polymorphonuclear leukocytes (PMN) and macrophage inflammatory protein 2 in the lungs, whereas histopathologic changes were less severe. In contrast, in response to the gram-positive cocci, the lpr animals had similar or lower numbers of PMN. We conclude that the Fas/FasL system contributes to the development of permeability changes and tissue injury during-gram negative bacterial pneumonia. The Fas/FasL system did not have a major role in the clearance of aerosolized bacteria from the lungs at the bacterial doses tested.
C1 Univ Washington, Sch Med, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA.
   Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA.
   VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA USA.
RP Martin, TR (reprint author), Pulm Res Lab, 151L,1660 S Columbian Way, Seattle, WA 98108 USA.
FU NHLBI NIH HHS [R01 HL062995, HL30542, HL 62995]
NR 30
TC 53
Z9 53
U1 0
U2 1
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 SEP
PY 2001
VL 69
IS 9
BP 5768
EP 5776
DI 10.1128/IAI.69.9.5768-5776.2001
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 464PB
UT WOS:000170540000067
PM 11500454
ER

PT J
AU Zachary, KC
   Bayne, PS
   Morrison, VJ
   Ford, DS
   Silver, LC
   Hooper, DC
AF Zachary, KC
   Bayne, PS
   Morrison, VJ
   Ford, DS
   Silver, LC
   Hooper, DC
TI Contamination of gowns, gloves, and stethoscopes with
   vancomycin-resistant enterococci
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article
ID INTENSIVE-CARE UNIT; FAECIUM; EPIDEMIOLOGY; BACTEREMIA; INFECTION;
   OUTBREAK; STRAINS; RISK
AB OBJECTIVE: To measure directly the rate of contamination, during routine patient examination, of gowns, gloves, and stethoscopes with vancomycin-resistant enterococci (VRE).
   SETTING: A large, academic, tertiary-care hospital.
   PATIENTS: Between January 1997 and December 1998, 49 patients colonized or infected with VRE were entered in the study.
   DESIGN: After routine examination, the examiner's glove fingertips, gown (the umbilical region and the cuffs), and stethoscope diaphragm were pressed onto Columbia colistin-nalidixic acid (CNA) agar plates with 5% sheep blood plus vancomycin 6 mug/mL. The stethoscope diaphragm was sampled again after cleaning with a 70% isopropanol wipe.
   RESULTS: VRE were isolated from at least 1 examiner site (gloves, gowns, or stethoscope) in 33 (67%) of 49 cases. Gloves were contaminated in 63%, gowns in 37%, and stethoscopes in 31%. All three items were positive for VRE in 24%. One case each had stethoscope and gown contamination without glove contamination. Only 1 (2%) of 49 stethoscopes was positive after wiping with an alcohol swab. Contamination at any site was more likely when the patient had a colostomy or ileostomy. Patients identified by rectal-swab culture alone were as likely to contaminate their examiners as were those identified by clinical specimens.
   CONCLUSIONS: Our study revealed a high rate of examiner contamination with VRE. The similar risk of contamination identified by surveillance and clinical cases reinforces concerns that patients not known to be colonized with VRE could serve as sources for dissemination. Wiping with alcohol is effective in decontaminating stethoscopes (Infect Control Hosp Epidemiol 2001;22:560-564).
C1 Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Infect Control Unit, Boston, MA 02114 USA.
RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, 55 Fruit St,GRJ 504, Boston, MA 02114 USA.
NR 17
TC 76
Z9 78
U1 0
U2 2
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0899-823X
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD SEP
PY 2001
VL 22
IS 9
BP 560
EP 564
DI 10.1086/501952
PG 5
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 493NV
UT WOS:000172230300006
PM 11732785
ER

PT J
AU Kahn, SE
AF Kahn, SE
TI Beta cell failure: causes and consequences
SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE
LA English
DT Article; Proceedings Paper
CT Symposium on Control of Postprandial Peaks and Hypoglycaemic Valleys of
   Diabetes
CY MAR, 2001
CL TELFES, AUSTRIA
SP Eli Lilly & Co
ID IMPAIRED GLUCOSE-TOLERANCE; DEPENDENT DIABETES-MELLITUS; INTRAVENOUS
   GLUCOSE; INSULIN-RESISTANCE; SECRETION; SENSITIVITY; RELEASE
AB In recent years a great deal of discussion has focused on the relative roles of insulin resistance and beta -cell dysfunction in the pathogenesis of type 2 diabetes. When considering their relative importance it is critical that the two variables are considered in concert. Alterations in insulin secretion are present in patients with type 2 diabetes and can be demonstrated in high risk individuals well before diagnosis. Loss of the early phase of insulin secretion can be demonstrated following oral or intravenous glucose administration. The relationship of early insulin secretion to insulin sensitivity in normal individuals is represented by a hyperbolic curve in keeping with the existence of a feedback loop. Deviations from standardised curves demonstrate defects in both insulin secretion and sensitivity in individuals who are at risk of developing diabetes. The reduction in the early phase insulin response results in impaired suppression of hepatic glucose production. Glucose output by the liver is not inversely proportionate to glucose influx, resulting in postprandial hyperglycaemia. Therapeutic approaches must address defects in both the early insulin response and insulin sensitivity. New oral agents that stimulate early insulin secretion and rapid-acting insulin analogues are targeting this early insulin secretion defect.
C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA.
   Univ Washington, Seattle, WA 98195 USA.
RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA.
OI Kahn, Steven/0000-0001-7307-9002
NR 22
TC 8
Z9 10
U1 0
U2 0
PU MEDICOM INTERNATIONAL
PI SURREY
PA CHURSTON HOUSE, PORTSMOUTH RD, ESHER, SURREY KT10 9AD, ENGLAND
SN 1368-5031
J9 INT J CLIN PRACT
JI Int. J. Clin. Pract.
PD SEP
PY 2001
SU 123
BP 13
EP 18
PG 6
WC Medicine, General & Internal; Pharmacology & Pharmacy
SC General & Internal Medicine; Pharmacology & Pharmacy
GA 478VA
UT WOS:000171365000004
PM 11594291
ER

PT J
AU Asea, A
   Mallick, R
   Lechpammer, S
   Ara, G
   Teicher, BA
   Fiorentino, S
   Stevenson, MA
   Calderwood, SK
AF Asea, A
   Mallick, R
   Lechpammer, S
   Ara, G
   Teicher, BA
   Fiorentino, S
   Stevenson, MA
   Calderwood, SK
TI Cyclooxygenase inhibitors are potent sensitizers of prostate tumours to
   hyperthermia and radiation
SO INTERNATIONAL JOURNAL OF HYPERTHERMIA
LA English
DT Article
DE cyclooxygenase; hyperthermia; prostate cancer; non-steroidal
   anti-inflammatory drugs; radiation; thermotolerance
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NF-KAPPA-B; HEAT-SHOCK RESPONSE;
   SODIUM-SALICYLATE; GENE-TRANSCRIPTION; MAMMALIAN-CELLS; CARCINOMA-CELLS;
   HUMAN MONOCYTES; EXPRESSION; THERMOTOLERANCE
AB It has previously been demonstrated that hyperthermia can activate prostaglandin synthesis and that prostaglandins are protective against hyperthermia. This study examined the use of inhibitors of prostaglandin synthesis on the response of prostate tumours to hyperthermia. The non-steroidal anti-inflammatory drugs (NSAID) ibuprofen and sulindac, known cyclooxygenase inhibitors that inhibit prostaglandin production, were effective hyperthermia sensitizers and augmented growth delay of DU-145 and PC-3 prostate tumours to combined radiation and hyperthermia treatment protocols. Pre-treatment of mice with ibuprofen and sulindac at hyperthermia sensitizing doses resulted in significant (p < 0.01) inhibition of hyperthemia-induced serum prostaglandin E-2. These findings indicate that NSAID may have both sensitizing effects on prostate tumour growth and may function by inhibiting prostaglandin synthesis.
C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   Hosp St Louis, Unite Lymphocyte & Canc, INSERM,U462, Inst Univ Hematol, Paris, France.
   Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Boston, MA 02215 USA.
RP Calderwood, SK (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA.
RI Asea, Alexzander/I-4112-2013; 
OI Asea, Alexzander/0000-0003-3592-3481; FIORENTINO,
   SUSANA/0000-0002-4664-0682
FU NCI NIH HHS [3PO1CA31303]
NR 32
TC 8
Z9 8
U1 0
U2 0
PU TAYLOR & FRANCIS LTD
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
SN 0265-6736
J9 INT J HYPERTHER
JI Int. J. Hyperthermia
PD SEP
PY 2001
VL 17
IS 5
BP 401
EP 414
PG 14
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 469UU
UT WOS:000170835100003
PM 11587078
ER

PT J
AU Lui, WO
   Tanenbaum, DM
   Larsson, C
AF Lui, WO
   Tanenbaum, DM
   Larsson, C
TI High level amplification of 1p32-33 and 2p22-24 in small cell lung
   carcinomas
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE comparative genomic hybridization; small cell lung cancer; high level
   amplification
ID COMPARATIVE GENOMIC HYBRIDIZATION; FAMILY DNA AMPLIFICATION;
   TUMOR-SUPPRESSOR GENES; C-MYC ONCOGENE; CYTOGENETIC ABNORMALITIES; 3P
   DELETION; ALLELE LOSS; SHORT ARM; N-MYC; CANCER
AB Small cell lung cancer (SCLC) is a frequently occurring, highly aggressive tumor with a generally poor clinical outcome. In order to approach the genetic mechanisms behind the tumor progression, a general screen for DNA copy number alterations was performed using comparative genomic hybridization (CGH). In the series of 23 cases analyzed, CGH alterations were frequently detected ranging from 9 to 22 abnormalities in the individual tumors. The most frequent losses were detected on chromosome arms 3p (23/23), 13q14-21 (23/23), 4p (20/23), 4q (20/23), and 2q22-24 (18/23), while gains preferentially involved chromosome arms 19p (18/23), 19q (17/23), 1p31-35 (15/23), 17q22-25 (11/23), and 5p14-15.3 (9/23). In addition, high level amplification at chromosome arms 1p32-33 and 2p22-24 were found in three and two cases, respectively. Candidate genes for these amplifications include the I-MYC (1p32) and n-MYC (2p24.1) oncogenes, which have been previously found to be overexpressed in SCLC. Taken together, the findings demonstrate a high level of chromosomal instability in SCLC, which is well in agreement with the highly malignant phenotype of this tumor type. Subchromosomal regions involved in gains and losses were delineated and the amplifications of 1p32-33 and 2p22-24 were demonstrated, thus providing starting points for the exact characterization of molecular events involved in SCLC tumor progression.
C1 Karolinska Hosp, Dept Mol Med, Endocrine Tumor Unit, SE-17176 Stockholm, Sweden.
   Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA.
RP Lui, WO (reprint author), Karolinska Hosp, Dept Mol Med, Endocrine Tumor Unit, CMM L8-01, SE-17176 Stockholm, Sweden.
RI Lui, Weng-Onn/G-6703-2013
OI Lui, Weng-Onn/0000-0003-4717-4473
FU NCI NIH HHS [5T34 CA72320-03]
NR 59
TC 13
Z9 13
U1 0
U2 1
PU PROFESSOR D A SPANDIDOS
PI ATHENS
PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE
SN 1019-6439
J9 INT J ONCOL
JI Int. J. Oncol.
PD SEP
PY 2001
VL 19
IS 3
BP 451
EP 457
PG 7
WC Oncology
SC Oncology
GA 462KF
UT WOS:000170418700002
PM 11494021
ER

PT J
AU Paganetti, H
   Goitein, M
AF Paganetti, H
   Goitein, M
TI Biophysical modelling of proton radiation effects based on amorphous
   track models
SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
LA English
DT Article
ID RELATIVE BIOLOGICAL EFFECTIVENESS; LOW-ENERGY PROTONS; CELLULAR
   RADIOSENSITIVITY PARAMETERS; ULTRASOFT X-RAYS; V79 CELLS; HIGH-LET;
   MAMMALIAN-CELLS; INACTIVATION; SURVIVAL; THERAPY
AB Purpose: To define a photon-equivalent dose in charged particle therapy one needs to know the RBE (Relative Biological Effectiveness) in the target region as well as in the surrounding tissue. RBE estimates are difficult since both the physical input parameters, i.e. LET distributions, and. even more so, the biological input parameters, i.e. cell nucleus size and local response, are not known in general. Track structure theory provides a basis for predicting close response curves for particle irradiation. There are (at least) two somewhat different algorithms: the Amorphous Track Partition model (ATP) and the Amorphous Track Local effect model (ATL). Both have been reported to give good agreement with observed radiobiological data. Ve were interested in a general comparison and in the predictive power of these models for protons.
   Materials and methods: We compared the principles of the two track structure approaches. The general dependencies of the model predictions on the input parameters are investigated. The model predictions for protons with respect to cell survival of V79 cells are compared with measurements.
   Results: Although based on similar assumptions, the application of track structure theory in terms of the computational procedure is different for the two models. The ATP model provides a set of equations to predict inter- and intratrack radiation response,whereas the ATL model is based on Monte Carlo simulations. One conceptual difference is the use of average doses in subtargets in the ATP model compared with the use of local doses in infinitesimal compartments in the ATL model. The ATP concept introduces an empirical scaling of the cross-section from subcellular to cellular response. The ATL concept inherently requires a critical adjustment of parameters handling the high local dose region near the track centre. The models predict proton survival curves reasonably well but neither shows good agreement With experimental data over the entire range of proton energy and absorbed dose considered.
   Conclusion: Designed for heavy ion applications, the models show weaknesses in the prediction of proton radiation effects. Amorphous track models arc based on assumptions about the properties of the biological target and the radiation field that can lie questioned. In particular, the assumption of subtargets and the multitarget/single-hit response function on one hand and the parameterization of radial dose and high dose cellular response on the other hand leave question marks.
C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
FU NCI NIH HHS [CA21239]
NR 70
TC 42
Z9 42
U1 0
U2 3
PU TAYLOR & FRANCIS LTD
PI LONDON
PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND
SN 0955-3002
J9 INT J RADIAT BIOL
JI Int. J. Radiat. Biol.
PD SEP
PY 2001
VL 77
IS 9
BP 911
EP 928
DI 10.1080/09553000110066059
PG 18
WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine &
   Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Nuclear Science &
   Technology; Radiology, Nuclear Medicine & Medical Imaging
GA 475TX
UT WOS:000171184900001
PM 11576451
ER

PT J
AU Zissiadis, Y
   Dutton, S
   Kieran, M
   Goumnerova, L
   Scott, RM
   Kooy, HM
   Tarbell, NJ
AF Zissiadis, Y
   Dutton, S
   Kieran, M
   Goumnerova, L
   Scott, RM
   Kooy, HM
   Tarbell, NJ
TI Stereotactic radiotherapy for pediatric intracranial germ cell tumors
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE intracranial germ cell tumor; stereotactic radiation therapy
ID CENTRAL NERVOUS-SYSTEM; RADIATION-THERAPY; IRRADIATION; PINEAL;
   COMPLICATIONS; CHEMOTHERAPY; EXPERIENCE; DEPRESSION; GERMINOMA; LEUKEMIA
AB Purpose: Intracranial germ cell tumors are rare, radiosensitive tumors seen most commonly in the second and third decades of life. Radiotherapy alone has been the primary treatment modality for germinomas, and is used with chemotherapy for nongerminomatous tumors. Stereotactic radiotherapy techniques minimize the volume of surrounding normal tissue irradiated and, hence, the late radiation morbidity. This study reports our experience with stereotactic radiotherapy in this group of tumors.
   Methods and Materials: Between December 1992 and December 1998, 18 patients with intracranial germ cell tumors were treated with stereotactic radiotherapy. A total of 23 histologically proven tumors were treated. Thirteen patients had a histologic diagnosis of germinoma, and 5 patients had germinoma with nongerminomatous elements. Of those patients with a histologic diagnosis of germinoma, 5 had multiple midline tumors. The median age of the patients was 12.9 years (range, 5.6-17.5 years).
   Results: A boost using stereotactic radiotherapy was delivered to 19 tumors following whole-brain radiation in 8 cases and craniospinal radiation in 11 cases. Three tumors were treated with stereotactic radiotherapy to the tumor volume alone following chemotherapy, and 1 tumor received a boost using stereotactic radiosurgery following craniospinal radiation. A median dose of 2520 cGy (range, 1500-3600) cGy was given to the whole brain, and a median dose of 2160 (range, 2100-2600) cGy was given to the spinal field. The median boost dose to the tumor was 2600 (range, 2160-3600) cGy, given by stereotactic radiotherapy delivered to the 95% isodose line. At a median follow-up time of 40 (range, 12-73) months, no local or marginal recurrences were reported in patients with germinoma. Two patients with nongerminomatous tumors have relapsed. One had elevation of tumor markers only at 37 months following treatment, and the other had persistent disease following chemotherapy and radiation therapy. Eight patients documented pituitary-hypothalamic dysfunction; in 7 (87.5%) of these patients, the dysfunction was present before commencing radiotherapy. Four patients (22%) developed newly diagnosed diabetes insipidus following surgery. Three patients (17%) received antidepressant medication at follow-up.
   Conclusion: Our series shows that stereotactic radiotherapy is achievable and well tolerated in this group of patients. Longer follow-up is required to fully assess the impact on long-term toxicity. Psychologic assessment of mood and affect should be performed as part of routine follow-up in this group of adolescent children. (C) 2001 Elsevier Science Inc.
C1 Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
   Prince Wales Hosp, Dept Radiat Oncol, Randwick, NSW 2031, Australia.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Dutton, S (reprint author), Childrens Hosp, Dept Radiat Oncol, 300 Longwood Ave, Boston, MA 02115 USA.
OI Kieran, Mark/0000-0003-2184-7692
NR 26
TC 16
Z9 16
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 SEP 1
PY 2001
VL 51
IS 1
BP 108
EP 112
DI 10.1016/S0360-3016(01)01569-3
PG 5
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 468EM
UT WOS:000170745200017
PM 11516859
ER

PT J
AU Fitzek, MM
   Thornton, AF
   Harsh, G
   Rabinov, JD
   Munzenrider, JE
   Lev, M
   Ancukiewicz, M
   Bussiere, M
   Hedley-Whyte, ET
   Hochberg, FH
   Pardo, FS
AF Fitzek, MM
   Thornton, AF
   Harsh, G
   Rabinov, JD
   Munzenrider, JE
   Lev, M
   Ancukiewicz, M
   Bussiere, M
   Hedley-Whyte, ET
   Hochberg, FH
   Pardo, FS
TI Dose-escalation with proton/photon irradiation for Daumas-Duport
   lower-grade glioma: Results of an institutional phase I/II trial
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
DE dose escalation; glioma; protons; radiation therapy
ID THERAPY-ONCOLOGY-GROUP; RADIATION-THERAPY; MALIGNANT GLIOMAS;
   GLIOBLASTOMA-MULTIFORME; ANAPLASTIC ASTROCYTOMA; CHEMOTHERAPY;
   MANAGEMENT; RADIOTHERAPY; PATTERNS
AB Purpose: The role of dose escalation with proton/photon radiotherapy in lower-grade gliomas was assessed in a prospective Phase I/II trial. We report the results in terms of local control, toxicity, and survival.
   Materials and Methods: Twenty patients with Grade 2/4 (n = 7) and Grade 3/4 (n = 13) gliomas according to the Daumai-Duport classification were treated on a prospective institutional protocol at Massachusetts General Hospital/Harvard Cyclotron Laboratory between 1993 and 1996. Doses prescribed to the target volumes were 68.2 cobalt Gray equivalent (CGE, 1 proton Gray = 1.1 CGE) to gross tumor in Grade 2 lesions and 79.7 CGE in Grade 3 lesions. Fractionation was conventional, with 1.8 to 1.92 CGE once per day. Eligibility criteria included age between 18 and 70 years, biopsy-proven Daumas-Duport Grade 2/4 or 3/4 malignant glioma, Karnofsky performance score of 70 or greater, and supratentorial tumor. Median age of the patient population at diagnosis was 35.9 years (range 19-49). Ten tumors were mixed gliomas, one an oligodendroglioma.
   Results: Five patients underwent biopsy, 12 a subtotal resection, and 3 a gross total resection. Median interval from surgery to first radiation treatment was 2.9 months. Actuarial 5-year survival rate for Grade 2 lesions was 71% as calculated from diagnosis (median survival not yet reached); actuarial 5-year survival for Grade 3 lesions was 23% (median 29 months). Median follow-up is 61 months and 55 months for 4 patients alive with Grade 2 and 3 patients alive with Grade 3 lesions, respectively. Three patients with Grade 2 lesions died from tumor recurrence, whereas 2 of the 4 survivors have evidence of radiation necrosis. Eight of 10 patients who have died with Grade 3 lesions died from tumor recurrence, 1 from pulmonary embolus, and 1 most likely from radiation necrosis. One of 3 survivors in this group has evidence of radiation necrosis.
   Conclusion: Tumor recurrence was neither prevented nor noticeably delayed in our patients relative to published series on photon irradiation. Dose escalation using this fractionation scheme and total dose delivered failed to improve outcome for patients with Grade 2 and 3 gliomas. (C) 2001 Elsevier Science Inc.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
RP Fitzek, MM (reprint author), Univ Essen Gesamthsch, Dept Radiat Oncol, Hufelandstr 55, D-45122 Essen, Germany.
FU NCI NIH HHS [P01 CA 21239]
NR 24
TC 28
Z9 32
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 SEP 1
PY 2001
VL 51
IS 1
BP 131
EP 137
DI 10.1016/S0360-3016(01)01589-9
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA 468EM
UT WOS:000170745200020
PM 11516862
ER

PT J
AU Dewhirst, FE
   Paster, BJ
   Tzellas, N
   Coleman, B
   Downes, J
   Spratt, DA
   Wade, WG
AF Dewhirst, FE
   Paster, BJ
   Tzellas, N
   Coleman, B
   Downes, J
   Spratt, DA
   Wade, WG
TI Characterization of novel human oral isolates and cloned 16S rDNA
   sequences that fall in the family Coriobacteriaceae: description of
   Olsenella gen. nov., reclassification of of Lactobacillus uli as
   Olsenella uli comb. nov and description of Olsenella profusa sp nov.
SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY
LA English
DT Article
DE Atopobium; Coriobacteriaceae; Olsenella; rRNA; phylogeny
ID PHENOTYPIC EVIDENCE; ATOPOBIUM
AB The diversity of organisms present in the subgingival pockets of patients with periodontitis and acute necrotizing ulcerative gingivitis (ANUG) were examined previously. The 16S rRNA genes of subgingival plaque bacteria were amplified using PCR with a universal forward primer and a spirochaete-selective reverse primer. The amplified DNA was cloned into Escherichia coli. In one subject with ANUG, 70 clones were sequenced. Seventy-five per cent of the clones were spirochaetal, as expected. Twelve of the remaining clones fell into two clusters that represent novel phylotypes in the family Coriobacteriaceae. The first novel phylotype was most closely related to Atopobium rimae (98% similarity). The phylotype probably represents a novel Atopobium species, but will not be named until cultivable strains are obtained. The second novel phylotype was only 91% similar to described Atopobium species and 84% similar to Coriobacterium glomerans. The 16S rRNA sequences of the type strain of Lactobacillus uli and a strain representing the Moores' Eubacterium group D52 were determined as part of on ongoing sequence analysis of oral bacteria. The sequence for L. uli was more than 99.8% similar to sequences for the second clone phylotype. it therefore appears that the second clone phylotype and L. uli represent the same species. The sequence for the Eubacterium D52 strain was 95.6% similar to that of L. uli. The G+C content of the DNA of L. uli and Eubacterium D52 is 63-64 mol%. These organisms are thus distinct from the neighbouring genus Atopobium, which has a DNA G+C content of 35-46 mol%. A new genus, Olsenella gen. nov., is proposed for these two species on the basis of phenotypic characteristics and 16S rRNA sequence analysis to include Olsenella uli comb. nov. and Olsenella profusa sp. nov.
C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Oral Biol, Boston, MA 02115 USA.
   Univ London Kings Coll, Guys Hosp, Guys Kings & St Thomas Dent Inst, Dept Oral Microbiol, London SE1 9RT, England.
RP Dewhirst, FE (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA.
RI Spratt, David/B-6237-2009
FU NIDCR NIH HHS [DE11443, DE-10374]
NR 24
TC 61
Z9 63
U1 0
U2 9
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 SEP
PY 2001
VL 51
BP 1797
EP 1804
PN 5
PG 8
WC Microbiology
SC Microbiology
GA 475KH
UT WOS:000171162800023
PM 11594611
ER

PT J
AU Afshari, NA
   Azar, NF
   Afshari, MA
   Azar, DT
AF Afshari, NA
   Azar, NF
   Afshari, MA
   Azar, DT
TI Corneal transplantation in children
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID PENETRATING KERATOPLASTY; PEDIATRIC KERATOPLASTY; INFANTS; SURVIVAL
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Afshari, NA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 26
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 1
EP 7
DI 10.1097/00004397-200110000-00003
PG 7
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500002
PM 11698731
ER

PT J
AU Graham, MAR
   Azar, NF
   Dana, MR
AF Graham, MAR
   Azar, NF
   Dana, MR
TI Visual rehabilitation in children with congenital hereditary endothelial
   dystrophy
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID PENETRATING KERATOPLASTY; LINKAGE
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Graham, MAR (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 23
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 9
EP 18
DI 10.1097/00004397-200110000-00004
PG 10
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500003
PM 11698732
ER

PT J
AU Lit, ES
   Azar, NF
   Jakobiec, FA
AF Lit, ES
   Azar, NF
   Jakobiec, FA
TI Pediatric ophthalmology: A subspecialty perspective - Preface
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Editorial Material
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP XVII
EP XVII
DI 10.1097/00004397-200110000-00002
PG 1
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500001
ER

PT J
AU Primack, JD
   Azar, NF
   Azar, DT
AF Primack, JD
   Azar, NF
   Azar, DT
TI Pediatric refractive surgery
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID IN-SITU KERATOMILEUSIS; LASER PHOTOREFRACTIVE KERATECTOMY;
   EXCIMER-LASER; HIGH MYOPIA; RADIAL KERATOTOMY; MODERATE MYOPIA;
   CHILDREN; HYPEROPIA; EPIKERATOPHAKIA; ASTIGMATISM
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Primack, JD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 45
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 19
EP 34
DI 10.1097/00004397-200110000-00005
PG 16
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500004
PM 11698735
ER

PT J
AU Faberowski, N
   Green, J
   Walton, DS
AF Faberowski, N
   Green, J
   Walton, DS
TI Angle closure in children
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID ECTOPIA LENTIS; GLAUCOMA
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Faberowski, N (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 14
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 35
EP 41
DI 10.1097/00004397-200110000-00006
PG 7
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500005
PM 11698736
ER

PT J
AU Garza, G
   Fay, A
   Rubin, PAD
AF Garza, G
   Fay, A
   Rubin, PAD
TI Treatment of pediatric vascular lesions of the eyelid and orbit
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID PORT-WINE STAINS; INTRALESIONAL CORTICOSTEROID INJECTION; PERIOCULAR
   CAPILLARY HEMANGIOMA; PULSED-DYE-LASER; VENOUS MALFORMATIONS;
   KIMURAS-DISEASE; CHILDREN; INFANCY; CLASSIFICATION; LYMPHANGIOMA
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Garza, G (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
NR 64
TC 9
Z9 11
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 43
EP 55
DI 10.1097/00004397-200110000-00007
PG 13
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500006
PM 11698737
ER

PT J
AU Tan, AD
   Rubin, PAD
   Sutula, FC
   Remulla, HD
AF Tan, AD
   Rubin, PAD
   Sutula, FC
   Remulla, HD
TI Congenital nasolacrimal duct obstruction
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID DACRYOCYSTORHINOSTOMY; INTUBATION; CHILDREN; SUCCESS; AGE
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Tan, AD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 41
TC 8
Z9 10
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 57
EP 69
DI 10.1097/00004397-200110000-00008
PG 13
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500007
PM 11698738
ER

PT J
AU Jain, A
   Rubin, PAD
AF Jain, A
   Rubin, PAD
TI Orbital cellulitis in children
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID SUBPERIOSTEAL ABSCESS; COMPUTERIZED-TOMOGRAPHY; DEFEROXAMINE THERAPY;
   VISUAL-LOSS; MANAGEMENT; RETINOBLASTOMA; MUCORMYCOSIS; INFECTIONS;
   DIAGNOSIS; CHILDHOOD
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Jain, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 55
TC 34
Z9 40
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 71
EP 86
DI 10.1097/00004397-200110000-00009
PG 16
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500008
PM 11698739
ER

PT J
AU Chandler, DB
   Rubin, PAD
AF Chandler, DB
   Rubin, PAD
TI Developments in the understanding and management of pediatric orbital
   fractures
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID BLOW-OUT FRACTURES; CRANIOFACIAL SURGERY; MIDFACIAL FRACTURES;
   COMPUTED-TOMOGRAPHY; FACIAL FRACTURES; RIGID FIXATION; TRAUMA; FLOOR;
   CHILDREN; INJURY
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Chandler, DB (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 36
TC 12
Z9 12
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 87
EP 104
DI 10.1097/00004397-200110000-00010
PG 18
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500009
PM 11698740
ER

PT J
AU Shivaram, SM
   Engle, EC
   Petersen, RA
   Robb, RM
AF Shivaram, SM
   Engle, EC
   Petersen, RA
   Robb, RM
TI Congenital fibrosis syndromes
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID DUANES RETRACTION SYNDROME; EXTRAOCULAR-MUSCLES; CHROMOSOME-12;
   OCULOMOTOR; ABSENCE; MAPS
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Shivaram, SM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 22
TC 2
Z9 6
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 105
EP 113
DI 10.1097/00004397-200110000-00011
PG 9
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500010
PM 11698741
ER

PT J
AU Newman-Toker, DE
   Rizzo, JF
AF Newman-Toker, DE
   Rizzo, JF
TI Neuro-ophthalmic diseases masquerading as benign strabismus
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID IDIOPATHIC INTRACRANIAL HYPERTENSION; SERIOUS NEUROLOGICAL DISEASE;
   ACQUIRED COMITANT ESOTROPIA; ONSET CONCOMITANT ESOTROPIA; ARNOLD-CHIARI
   MALFORMATION; DIVERGENCE PARALYSIS; I MALFORMATION; SIGN; DYSFUNCTION;
   EXOTROPIA
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Newman-Toker, DE (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
RI Newman-Toker, David/C-6083-2008
OI Newman-Toker, David/0000-0003-2789-4115
NR 59
TC 2
Z9 2
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 115
EP 127
DI 10.1097/00004397-200110000-00012
PG 13
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500011
PM 11698742
ER

PT J
AU Afshari, MA
   Hart, L
   Afshari, NA
   Mukai, S
AF Afshari, MA
   Hart, L
   Afshari, NA
   Mukai, S
TI Ophthalmic ultrasonography in children
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID ULTRASOUND; RETINOPATHY; PREMATURITY; SONOGRAPHY; EYES
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Afshari, MA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 24
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 153
EP 164
DI 10.1097/00004397-200110000-00014
PG 12
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500013
PM 11698744
ER

PT J
AU Youssri, AI
   Miller, JW
AF Youssri, AI
   Miller, JW
TI Best's macullar dystrophy
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID VITELLIFORM DYSTROPHY; DISEASE; GENE; LINKAGE; MUTATIONS; PROTEIN;
   FAMILY; VMD2; HOLE
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Youssri, AI (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 41
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 165
EP 171
DI 10.1097/00004397-200110000-00015
PG 7
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500014
PM 11698745
ER

PT J
AU Gauthier, D
   D'Amico, DJ
   Mukai, S
AF Gauthier, D
   D'Amico, DJ
   Mukai, S
TI von Hippell-Lindau disease
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID TUMOR-SUPPRESSOR GENE; ANGIOMATOSIS RETINAE; NATURAL-HISTORY;
   MANIFESTATIONS; LESIONS; FEATURES; FAMILIES
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Gauthier, D (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 35
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 173
EP 187
DI 10.1097/00004397-200110000-00016
PG 15
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500015
PM 11698746
ER

PT J
AU Jones, JH
   Kroll, AJ
   Lou, PL
   Ryan, EA
AF Jones, JH
   Kroll, AJ
   Lou, PL
   Ryan, EA
TI Coats' disease
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID RETINOBLASTOMA; DIAGNOSIS; LESIONS
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Jones, JH (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 19
TC 18
Z9 20
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 189
EP 198
DI 10.1097/00004397-200110000-00017
PG 10
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500016
PM 11698747
ER

PT J
AU Samson, CM
   Ekong, A
   Foster, CS
AF Samson, CM
   Ekong, A
   Foster, CS
TI Uveitis in children: Diagnosis and management
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID BEHCETS-DISEASE; SIMULATING RETINOBLASTOMA; CONGENITAL TOXOPLASMOSIS;
   OCULAR TOXOCARIASIS; CHILDHOOD; EYE; TUBERCULOSIS
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Samson, CM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 47
TC 4
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 199
EP 216
DI 10.1097/00004397-200110000-00018
PG 18
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500017
PM 11698748
ER

PT J
AU Yao, LJ
   Foster, CS
AF Yao, LJ
   Foster, CS
TI Tubulointerstitial nephritis and uveitis syndrome
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID ACUTE INTERSTITIAL NEPHRITIS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES;
   SYNDROME TINU SYNDROME; ANTERIOR UVEITIS; ASSOCIATION; GRANULOMAS;
   DISORDER; ADULT
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Yao, LJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 26
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 217
EP 221
DI 10.1097/00004397-200110000-00019
PG 5
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500018
PM 11698749
ER

PT J
AU Waheed, NK
   Miserocchi, E
   Foster, CS
AF Waheed, NK
   Miserocchi, E
   Foster, CS
TI Ocular concerns in juvenile rheumatoid arthritis
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID INTRAOCULAR-LENS IMPLANTATION; ANTERIOR UVEITIS; IRIDOCYCLITIS; THERAPY;
   METHOTREXATE; CHLORAMBUCIL; AMYLOIDOSIS; LATANOPROST; MANAGEMENT;
   SECONDARY
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Waheed, NK (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 53
TC 6
Z9 7
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 223
EP 234
DI 10.1097/00004397-200110000-00020
PG 12
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500019
PM 11698750
ER

PT J
AU Remulla, JF
   Tolentino, FI
AF Remulla, JF
   Tolentino, FI
TI Retinal detachment in Marfan's syndrome
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID SURGERY
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Remulla, JF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 23
TC 10
Z9 11
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 235
EP 240
DI 10.1097/00004397-200110000-00021
PG 6
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500020
PM 11698751
ER

PT J
AU Pantcheva, MB
   Mukai, S
AF Pantcheva, MB
   Mukai, S
TI Stem cells in ophthalmology
SO INTERNATIONAL OPHTHALMOLOGY CLINICS
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; NEURAL PROGENITOR CELLS; BONE-MARROW;
   TRANSPLANTATION; RETINA; RAT; DIFFERENTIATION; NEURONS; BRAIN; MOUSE
C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Pantcheva, MB (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
NR 59
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0020-8167
J9 INT OPHTHALMOL CLIN
JI Int. Ophthalmol. Clin.
PD FAL
PY 2001
VL 41
IS 4
BP 241
EP 254
DI 10.1097/00004397-200110000-00022
PG 14
WC Ophthalmology
SC Ophthalmology
GA 485QW
UT WOS:000171768500021
PM 11698752
ER

PT J
AU Berson, EL
   Grimsby, JL
   Adams, SM
   McGee, TL
   Sweklo, E
   Pierce, EA
   Sandberg, MA
   Dryja, TP
AF Berson, EL
   Grimsby, JL
   Adams, SM
   McGee, TL
   Sweklo, E
   Pierce, EA
   Sandberg, MA
   Dryja, TP
TI Clinical features and mutations in patients with dominant retinitis
   pigmentosa-1 (RP1)
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID GENE; EXPRESSION; FAMILY; LOCUS
AB PURPOSE. To survey patients with dominant retinitis pigmentosa (RP) for mutations in the RP1 gene to determine the spectrum of dominant mutations in this gene, to estimate the proportion of dominant RP caused by this gene, and to determine whether the clinical features of patients with PPI mutations differ from features of those with rhodopsin mutations.
   METHODS. A set of 241 patients who did not have mutations in the rhodopsin gene (based on previous work) formed the basis for the study. Of these patients, 117 had also been previously evaluated and were found not to carry mutations in the RDS gene. The single-strand conformation polymorphism (SSCP) method was used to search for sequence variants, which were then directly sequenced. The relatives of selected patients were recruited for segregation analyses. Clinical evaluations of patients included a measurement of Snellen visual acuity, final dark adaptation thresholds, visual fields, and ERGS. Clinical data were compared with those obtained earlier from a study of 128 patients with dominant rhodopsin mutations.
   RESULTS. Of the 241 patients, all were screened for the most common RP1 mutation (Arg677Ter), and 10 patients were found to have this mutation. In addition, an evaluation of a subset of 189 patients in whom the entire coding sequence was evaluated revealed the following mutations: Gln679Ter (1 case), Gly723Ter (2 cases), Glu729(1-bp del) (1 case), Leu762(5-bp del) (2 cases), and Asn763(4-bp del) (1 case). All of these mutations cosegregated with RP in the families of the index patients. Nine missense mutations that were each found in six or fewer patients were encountered. The segregation of eight of these was evaluated in the respective patients' families, and only one segregated with dominant RP. This cosegregating missense change was in cis with the nonsense mutation Gln679Ter. Although patients with RP1 mutations had, on average, slightly better visual acuity than patients with rhodopsin mutations, there was no statistically significant difference in final dark-adaptation thresholds, visual field diameters, or cone electroretinogram (ERG) amplitudes. Comparably aged patients with P-PI mutations had visual function that varied by approximately two orders of magnitude, based on visual fields and ERG amplitudes.
   CONCLUSIONS. Dominant RP1 alleles typically have premature nonsense codons occurring in the last exon of the gene and would be expected to encode mutant proteins that are only approximately one third the size of the wild-type protein, suggesting that a dominant negative effect rather than haplo-insufficiency is the mechanism leading to RP caused by RP1 mutations. On average, patients with RP1 mutations have slightly better visual acuity than patients with dominant rhodopsin mutations; otherwise, they have similarly severe disease. The wide range in severity among patients with RP1 mutations indicates that other genetic or environmental factors modulate the effect of the primary mutation.
C1 Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Cambridge, MA 02138 USA.
   Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA USA.
   Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Ocular Mol Genet Inst, Cambridge, MA 02138 USA.
RP Berson, EL (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
FU NEI NIH HHS [EY00169, EY08683]
NR 15
TC 41
Z9 46
U1 0
U2 2
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2001
VL 42
IS 10
BP 2217
EP 2224
PG 8
WC Ophthalmology
SC Ophthalmology
GA 469FL
UT WOS:000170803900011
PM 11527933
ER

PT J
AU Briggs, CE
   Rucinski, D
   Rosenfeld, PJ
   Hirose, T
   Berson, EL
   Dryja, TP
AF Briggs, CE
   Rucinski, D
   Rosenfeld, PJ
   Hirose, T
   Berson, EL
   Dryja, TP
TI Mutations in ABCR (ABCA4) in patients with Stargardt macular
   degeneration or cone-rod degeneration
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID DISEASE GENE ABCR; FUNDUS-FLAVIMACULATUS; RETINITIS-PIGMENTOSA;
   TRANSPORTER GENE; DYSTROPHY; MAPS; CLASSIFICATION; IDENTIFICATION;
   PROTEIN; ALLOWS
AB PURPOSE. To determine the spectrum of ABCR mutations associated with Stargardt macular degeneration and cone-rod degeneration (CRD).
   METHODS. One hundred eighteen unrelated patients with recessive Stargardt macular degeneration and eight with recessive CRD were screened for mutations in ABCR (ABCA4) by single-strand conformation polymorphism analysis. Variants were characterized by direct genomic sequencing. Segregation analysis was performed on the families of 20 patients in whom at least two or more likely pathogenic sequence changes were identified.
   RESULTS. The authors found 77 sequence changes likely to be pathogenic: 21 mill mutations (15 novel), 55 missense changes (26 novel), and one deletion of a consensus glycosylation site (also novel). Fifty-two patients with Stargardt macular degeneration (44% of those screened) and five with CRD each had two of these sequence changes or were homozygous for one of them. Segregation analyses in the families of 19 of these patients were informative and revealed that the index cases and all available affected siblings were compound heterozygotes or homozygotes. The authors found one instance of an apparently de novo mutation, Ile824Thr, in a patient. Thirty-seven (31%) of the 118 patients with Stargardt disease and one with CRD had only one likely pathogenic sequence change. Twenty-nine patients with Stargardt disease (25%) and two with CRD had no identified sequence changes.
   CONCLUSIONS. This report of 42 novel mutations brings the growing number of identified likely pathogenic sequence changes in ABCR. to approximately 250.
C1 Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA.
   Univ Miami, Sch Med, Bascom Palmer Eye Inst, Coral Gables, FL 33124 USA.
   Schepens Retina Associates, Boston, MA USA.
   Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA.
RP Dryja, TP (reprint author), Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA.
FU NEI NIH HHS [EY00169, EY08683]
NR 35
TC 87
Z9 90
U1 0
U2 3
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2001
VL 42
IS 10
BP 2229
EP 2236
PG 8
WC Ophthalmology
SC Ophthalmology
GA 469FL
UT WOS:000170803900013
PM 11527935
ER

PT J
AU Qaum, T
   Xu, QW
   Joussen, AM
   Clemens, MW
   Qin, WY
   Miyamoto, K
   Hassessian, H
   Wiegand, SJ
   Rudge, J
   Yancopoulos, GD
   Adamis, AP
AF Qaum, T
   Xu, QW
   Joussen, AM
   Clemens, MW
   Qin, WY
   Miyamoto, K
   Hassessian, H
   Wiegand, SJ
   Rudge, J
   Yancopoulos, GD
   Adamis, AP
TI VEGF-initiated blood-retinal barrier breakdown in early diabetes
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR-PERMEABILITY FACTOR; UP-REGULATION;
   IN-VIVO; CELLS; RAT; EXPRESSION; NEOVASCULARIZATION; HYPERPERMEABILITY;
   INFLAMMATION
AB PURPOSE. The objectives of this study were to (1) determine whether endogenous vascular endothelial growth factor (VEGF) triggers diabetic blood-retinal barrier breakdown, and (2) identify the site as well as phenotype of the hyperpermeable diabetic retinal vessels.
   METHODS. Retinal VEGF mRNA levels were quantified in I-week diabetic rats using the RNase protection assay. VEGF bioactivity was blocked via the systemic administration of a highly specific VEGF-neutralizing soluble Flt/F-c construct (VEGF TrapA.(10)). An inactive IL6 receptor/F-c construct (IL6R Trap) was used as an isotype control. Blood-retinal barrier breakdown was quantified using the Evans blue technique and was spatially localized with fluorescent microspheres.
   RESULTS. Retinal VEGF mRNA levels in 1-week diabetic animals were 3.2-fold higher than in nondiabetic controls (P < 0.0001). Similarly, retinal vascular permeability in 8-day diabetic animals was 1.8-fold higher than in normal nondiabetic controls (P < 0.05). Diabetes-induced blood-retinal barrier breakdown was dose-dependently inhibited with VEGF TrapA(40), with 25 mg/kg producing complete inhibition of the diabetes-induced increases (P < 0.05). Blood-retinal barrier breakdown in diabetic animals treated with solvent alone or IL6R Trap did not differ significantly from untreated diabetic animals (P <greater than> 0.05). Spatially, early blood-retinal barrier break-down was localized to the retinal venules and capillaries of the superficial retinal vasculature.
   CONCLUSIONS. Early blood-retinal barrier breakdown in experimental diabetes is VEGF dependent and is restricted, in part, to the venules and capillaries of the superficial inner retinal vasculature. VEGF inhibition should prove a useful therapeutic approach in the treatment of early diabetic blood-retinal barrier breakdown.
C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
   Harvard Univ, Childrens Hosp, Sch Med, Dept Surg Res, Boston, MA 02115 USA.
   Jining Med Coll, Affiliated Hosp, Dept Ophthalmol, Shandong, Peoples R China.
   Univ Cologne, Ctr Ophthalmol, Dept Viteoretinal Surg, D-5000 Cologne, Germany.
   Penn State Coll Med, Hershey, PA USA.
   Hop Maisonneuve Resemont, Ctr Rech Guy Bernier, Montreal, PQ, Canada.
   Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
   Regeneron Pharmaceut, Tarrytown, NY USA.
RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
FU NEI NIH HHS [EY11627, EY12611]
NR 33
TC 272
Z9 301
U1 3
U2 8
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0146-0404
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD SEP
PY 2001
VL 42
IS 10
BP 2408
EP 2413
PG 6
WC Ophthalmology
SC Ophthalmology
GA 469FL
UT WOS:000170803900035
PM 11527957
ER

PT J
AU Kujawa, SG
   Liberman, MC
AF Kujawa, SG
   Liberman, MC
TI Effects of olivocochlear feedback on distortion product otoacoustic
   emissions in guinea pig
SO JARO
LA English
DT Article
DE olivocochlear; otoacoustic emissions; outer hair cells; guinea pig;
   distortion products; reflex
ID COMPOUND ACTION-POTENTIALS; COCHLEAR DE-EFFERENTATION; AUDITORY-NERVE
   FIBERS; CONTRALATERAL SOUND; ACOUSTIC INJURY; RESPONSE PROPERTIES;
   HAIR-CELLS; STIMULATION; RECEPTOR; NEURONS
AB Activation of ipsilaterally responsive olivocochlear (OC) neurons by sound produces rapid, post-onset alterations in the 2f(1)-f(2) distortion product otoacoustic emission (DPOAE). The present study investigates the frequency and level dependence of this ipsilateral OC effect in the anesthetized guinea pig, compares its magnitude and sign to OC effects elicited by contralateral sound ("contralateral" OC effect), and characterizes the influence of such activity on steady-state DPOAE amplitude. DPOAEs were measured with fine time resolution in response to primary stimuli varied systematically in frequency and level. DPOAEs showed rapid and remarkably stereotyped post-onset amplitude alterations. These ipsilateral OC effects were greater for high (8-12 kHz) than for low (2-4 kHz) f(2) primary frequencies and for higher primary levels (70-80 dB SPL). For any f(2)/f(1) pair, the sign as well as the magnitude of the ipsilateral effects varied with primary level ratio. For example, with L-1 fixed at 75 and L-2 varied in 1-dB steps from 60 to 75 dB SPL, DPOAE amplitude underwent a stereotyped progresssion from post-onset increases at the lowest levels of the f(2) primary to post-onset decreases at the highest levels. At intermediate levels, near the region of sign change (L-2 = 5-10 dB below L-1), post-onset effects were often particularly large (as great as 20 dB). These large ipsilateral OC effects were always associated with "dips" in the DPOAE amplitude vs. level functions, and both disappeared after OC section. Although smaller in magnitude, contralateral OC effects were identical to ipsilateral effects in frequency and level dependence and in form.
C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otol & Laryngol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA.
RP Kujawa, SG (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA.
FU NIDCD NIH HHS [F32 DC00180, R01 DC00188, P30 DC005209]
NR 38
TC 55
Z9 59
U1 1
U2 2
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 1525-3961
J9 JARO
JI JARO
PD SEP
PY 2001
VL 2
IS 3
BP 268
EP 278
DI 10.1007/s101620010047
PG 11
WC Neurosciences; Otorhinolaryngology
SC Neurosciences & Neurology; Otorhinolaryngology
GA 476FU
UT WOS:000171216200007
PM 11669399
ER

PT J
AU Wilkes, W
   Fink, J
   Dhand, R
AF Wilkes, W
   Fink, J
   Dhand, R
TI Selecting an accessory device with a metered-dose inhaler: Variable
   influence of accessory devices on fine particle dose, throat deposition,
   and drug delivery with asynchronous actuation from a metered-dose
   inhaler
SO JOURNAL OF AEROSOL MEDICINE-DEPOSITION CLEARANCE AND EFFECTS IN THE LUNG
LA English
DT Article
DE aerosol; albuterol; bronchodilator; cascade impactor; inhalation therapy
ID AEROSOL DELIVERY; HOLDING CHAMBER; SPACER DEVICES; ASTHMA; SIZE
AB Accessory devices reduce common problems with metered-dose inhalers (MDIs), namely high oropharyngeal deposition of aerosol and incoordination between actuation and inhalation by the patient. The objective of this study was to systematically compare the performance of various accessory devices in vitro. MDIs were tested alone or in combination with four spacers (Toilet paper roll, Ellipse, Optihaler, Myst Assist) and five holding chambers (Aerochamber, Optichamber, Aerosol Cloud Enhancer, Medispacer, and Inspirease). An Anderson cascade impactor was used to measure aerosol mass median aerodynamic diameter (MMAD) and fine particle dose (MMAD < 4.7 mum). In separate experiments, the influence of asynchronous MDI actuation on drug delivery was determined with a simulated spontaneous breathing model. Compared with the MDI alone, all of the accessory devices reduced aerosol MMAD and increased lung-throat ratio (fine particle dose/throat impaction; p < 0.05 for both parameters). The fine particle dose of albuterol was 40% higher with the Ellipse (p < 0.01), was equivalent with the Toilet Paper Roll, Aerochamber, Optichamber, and Medispacer, and was 33-56% lower with the Optihaler, Myst Assist, Aerosol Cloud Enhancer, and Inspirease (p < 0.03). MDI actuation in synchrony with inspiration produced highest drug delivery; when MDI actuation occurred I-sec before inspiration or during exhalation, decrease in drug delivery with holding chambers (10-40% reduction) was less than that with spacers (40-90% reduction). Accessory device selection is complicated by variability in performance between devices, and in the performance of each device in different clinical settings. In vitro characterization of a MDI and accessory device could guide appropriate device selection in various clinical settings.
C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA.
RP Dhand, R (reprint author), Hines VA Hosp, Div Pulm & Crit Care Med, 111N,5th & Roosevelt Rd, Hines, IL 60141 USA.
NR 29
TC 23
Z9 27
U1 1
U2 2
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 0894-2684
J9 J AEROSOL MED
JI J. Aerosol Med.-Depos. Clear. Eff. Lung
PD FAL
PY 2001
VL 14
IS 3
BP 351
EP 360
DI 10.1089/089426801316970312
PG 10
WC Public, Environmental & Occupational Health; Respiratory System
SC Public, Environmental & Occupational Health; Respiratory System
GA 469MC
UT WOS:000170818600009
PM 11693847
ER

PT J
AU Geys, H
   Regan, MM
   Catalano, PJ
   Molenberghs, G
AF Geys, H
   Regan, MM
   Catalano, PJ
   Molenberghs, G
TI Two latent variable risk assessment approaches for mixed continuous and
   discrete outcomes from developmental toxicity data
SO JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS
LA English
DT Article
DE benchmark dose; clustered data; correlated probit models; Dale model;
   generalized estimating equations; odds ratio; pseudolikelihood
ID LONGITUDINAL DATA-ANALYSIS; GENERALIZED LINEAR-MODELS; TOXICOLOGY;
   BIVARIATE; REGRESSION; BINARY
AB Measurements of both continuous and discrete outcomes are encountered in many statistical problems. Here we consider the particular context of teratology studies, where quantitative risk assessment is aimed at determining the effect of dose on the probability that an individual fetus is malformed or of low birth weight, both being important measures of teratogenicity. We will introduce two different joint marginal mean models for outcomes of a mixed nature. First, we propose the Plackett-Dale approach, where for each binary outcome it is assumed that there exists an underlying latent variable. The latent malformation outcomes are then assumed to follow a Plackett distribution. The second approach we consider is a probit approach. Here it is assumed that there exists an underlying continuous variable for each binary outcome, so the joint distribution for weight and malformation can be assumed to follow a multivariate normal distribution. In both cases, specification of the full distribution will be avoided using pseudolikelihood and generalized estimating equations methodology, respectively. Quantitative risk assessment is illustrated using data from two developmental toxicology experiments.
C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Limburgs Univ Ctr, B-3590 Diepenbeek, Belgium.
NR 23
TC 18
Z9 18
U1 0
U2 1
PU AMER STATISTICAL ASSOC & INTERNATIONAL BIOMETRIC SOC
PI WASHINGTON
PA 1444 I ST NW, STE 700, WASHINGTON, DC 20005 USA
SN 1085-7117
J9 J AGRIC BIOL ENVIR S
JI J. Agric. Biol. Environ. Stat.
PD SEP
PY 2001
VL 6
IS 3
BP 340
EP 355
DI 10.1198/108571101317096550
PG 16
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
   Biology; Mathematics
GA 496RF
UT WOS:000172409200003
ER

PT J
AU Sriraman, V
   Niu, E
   Matias, JR
   Donahoe, PK
   MacLaughlin, DT
   Hardy, MP
   Lee, MM
AF Sriraman, V
   Niu, E
   Matias, JR
   Donahoe, PK
   MacLaughlin, DT
   Hardy, MP
   Lee, MM
TI Mullerian inhibiting substance inhibits testosterone synthesis in adult
   rats
SO JOURNAL OF ANDROLOGY
LA English
DT Article; Proceedings Paper
CT 25th Annual Meeting of the American-Society-of-Andrology
CY 2000
CL BOSTON, MA
SP Amer Soc Androl
DE Anti-Mullerian hormone; primary Leydig cells; p450c17; testis; androgen
   biosynthesis; steroidogenesis
ID MESSENGER-RIBONUCLEIC-ACID; FOLLICLE-STIMULATING-HORMONE; SIDE-CHAIN
   CLEAVAGE; LEYDIG-CELLS; LUTEINIZING-HORMONE; II RECEPTOR;
   SEXUAL-DIFFERENTIATION; STEROIDOGENIC ENZYMES; AUTOCRINE REGULATION;
   EXPRESSION
AB Mullerian inhibiting substance (MIS) is a gonadal hormone that causes regression of the Mullerian ducts during male sexual differentiation. Postnatally, MIS inhibits the proliferation and differentiation of immature Leydig cells, and transgenic mice that overexpress MIS have decreased serum testosterone concentrations. To elucidate the effects of MIS on androgen regulation in the postnatal testis, we examined testosterone synthesis in adult Sprague-Dawley rats following intratesticular and intraperitoneal injections of MIS. Intratesticular MIS injection achieved high local concentrations of MIS (574.0 +/- 60.0 ng/mL) at 4 hours, with a corresponding decline in serum testosterone concentrations to 0.7 +/-0.1 ng/mL, compared to 1.1 +/-0.2 ng/mL with intraperitoneal MIS and 1.6 +/-0.1 ng/mL with intratesticular vehicle (IT-Veh) (P<.001). Intratesticular administration of MIS (IT-MIS) resulted in much higher serum and testicular interstitial fluid MIS concentrations than the intraperitoneal route. To directly examine the testosterone production rate in MIS-treated animals, we isolated Leydig cells from MIS and vehicle-injected testes. Primary Leydig cells exposed to MIS had a lower testosterone production rate and decreased expression of p450c17 (hydroxylase/lyase) and luteinizing hormone (LH) receptor mRNAs than that of vehicle-injected controls or the noninjected contralateral testis. In conclusion, intratesticular administration of MIS caused a decline in serum testosterone concentrations by decreasing the rate of testosterone biosynthesis, confirming that MIS can regulate adult Leydig cell androgen production. The ability of MIS to down-regulate mRNA expression of the p450c17 and LH receptor genes suggests that this effect is mediated transcriptionally. These data indicate that, in addition to its role in embryonic differentiation of the male reproductive tract, MIS has a regulatory function in the postnatal testis. We conclude that one such function is for MIS to directly inhibit adult Leydig cell steroidogenesis.
C1 Duke Univ, Med Ctr, Div Pediat Endocrinol, Dept Pediat, Durham, NC 27710 USA.
   Rockefeller Univ, New York, NY 10021 USA.
   Populat Council, New York, NY 10021 USA.
   Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA.
RP Duke Univ, Med Ctr, Div Pediat Endocrinol, Dept Pediat, 308 Bell Bldg,Box 3080, Durham, NC 27710 USA.
EM Lee00l40@mc.duke.edu
OI Lee, Mary/0000-0002-7204-4884
FU NICHD NIH HHS [R01 HD32588, K02 HD01367, R29 HD36768]
NR 48
TC 38
Z9 40
U1 0
U2 2
PU AMER SOC ANDROLOGY, INC
PI LAWRENCE
PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA
SN 0196-3635
EI 1939-4640
J9 J ANDROL
JI J. Androl.
PD SEP-OCT
PY 2001
VL 22
IS 5
BP 750
EP 758
PG 9
WC Andrology
SC Endocrinology & Metabolism
GA 464RZ
UT WOS:000170546700008
PM 11545286
ER

PT J
AU Clohisy, JC
   Harris, WH
AF Clohisy, JC
   Harris, WH
TI Matched-pair analysis of cemented and cementless acetabular
   reconstruction in primary total hip arthroplasty
SO JOURNAL OF ARTHROPLASTY
LA English
DT Article
DE total hip arthroplasty; acetabular fixation; aseptic loosening
ID REPLACEMENT; COMPONENT
AB In a matched-pair study of primary total hip arthroplasty, 45 all-polyethylene cemented acetabular components were compared with 45 cementless, hemispheric, titanium acetabular components. At 9 to 12 years, I of the cemented acetabular components was revised for aseptic loosening, and 14 (31%) were radiographically loose. Nine (20%) cemented acetabular components had pelvic osteolysis. In the cementless acetabular component group, 2 well-fixed components were revised. No components were radiographically loose, and 3 (7%) had pelvic osteolysis. Thirty-eight (97%) of the patients in each group were satisfied with the surgery. The clinical results of the cemented and cementless components were excellent. The cementless components had less loosening (P < .001) than the cemented components.
C1 Washington Univ, Sch Med, Dept Orthopaed Surg, St Louis, MO USA.
RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, GrJ 1126,35 Fruit St, Boston, MA 02114 USA.
NR 36
TC 26
Z9 30
U1 0
U2 0
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 0883-5403
J9 J ARTHROPLASTY
JI J. Arthroplast.
PD SEP
PY 2001
VL 16
IS 6
BP 697
EP 705
DI 10.1054/arth.2001.24447
PG 9
WC Orthopedics
SC Orthopedics
GA 469GF
UT WOS:000170805700003
PM 11547367
ER

PT J
AU Abboud, SL
   Woodruff, K
   Ghosh-Choudhury, N
AF Abboud, SL
   Woodruff, K
   Ghosh-Choudhury, N
TI Role of CSF-1 in breast cancer cell-mediated osteolytic lesions.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA.
   S Texas Vet Hlth Care Syst, San Antonio, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC 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 SEP
PY 2001
VL 16
SU 1
BP S453
EP S453
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001324
ER

PT J
AU Aikawa, T
   Koike, T
   Segre, GV
   Colvin, J
   Ornitz, D
   Lee, K
AF Aikawa, T
   Koike, T
   Segre, GV
   Colvin, J
   Ornitz, D
   Lee, K
TI FGF signaling through FGFR1 or FGFR2 is a negative regulator of
   chondrocytic growth in fetal growth plate.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02114 USA.
   Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S188
EP S188
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000208
ER

PT J
AU Aikawa, T
   Segre, GV
   Lee, K
AF Aikawa, T
   Segre, GV
   Lee, K
TI FGF inhibits chondrocytic growth through induction of p21 and subsequent
   inactivation of cyclin E-cdk2.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA USA.
   Harvard Univ, Sch Med, Endocrine Unit, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S188
EP S188
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000207
ER

PT J
AU Bastepe, M
   Pincus, JE
   Juppner, H
AF Bastepe, M
   Pincus, JE
   Juppner, H
TI Positional dissociation between the genetic mutation responsible for
   pseudohypoparathyroidism type Ib and the associated methylation defect
   at exon A/B: Evidence for a long-range regulatory element within the
   imprinted GNAS1 locus.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S417
EP S417
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001174
ER

PT J
AU Battaglino, R
   Kim, D
   Stashenko, P
AF Battaglino, R
   Kim, D
   Stashenko, P
TI c-myc is required for osteoclastogenesis.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Forsyth Inst, Boston, MA USA.
   Harvard Univ, Sch Dent Med, Boston, MA 02115 USA.
RI battaglino, ricardo/D-2892-2015
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S153
EP S153
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000070
ER

PT J
AU Calvi, LM
   Shin, HI
   Knight, MC
   Saxton, JM
   Kronenberg, HM
   Schipani, E
AF Calvi, LM
   Shin, HI
   Knight, MC
   Saxton, JM
   Kronenberg, HM
   Schipani, E
TI In vivo expression of a constitutively active PTH/PTHrP receptor (PPR)
   in odontoblasts (ODs) alters OD and ameloblast (AB) function and
   maturation.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
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 SEP
PY 2001
VL 16
SU 1
BP S547
EP S547
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001736
ER

PT J
AU Chen, C
   Sakai, Y
   Demay, MB
AF Chen, C
   Sakai, Y
   Demay, MB
TI Alopecia in VDR null mice is secondary to a keratinocyte defect and can
   be prevented by targeting expression of the human VDR to keratinocytes
   in vivo.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S183
EP S183
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000186
ER

PT J
AU Chung, U
   Long, F
   McMahon, J
   McMahon, A
   Kronenberg, H
AF Chung, U
   Long, F
   McMahon, J
   McMahon, A
   Kronenberg, H
TI Smoothened is required for osteogenesis in endochondral bone
   development.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S144
EP S144
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000032
ER

PT J
AU Divieti, P
   John, MR
   Juppner, H
   Bringhurst, FR
AF Divieti, P
   John, MR
   Juppner, H
   Bringhurst, FR
TI In vitro inhibition of bone resorption by human PTH(7-84).
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S307
EP S307
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000695
ER

PT J
AU Eckstein, F
   Mueller, R
   Lochmuller, EM
AF Eckstein, F
   Mueller, R
   Lochmuller, EM
TI Experimental determination of mechanical failure loads at the femur,
   spine and radius, and their correlation with DXA, QCT, pQCT, and
   quantitative ultrasound.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Inst Anat, Musculoskeletal Res Grp, Munich, Germany.
   Harvard Univ, Sch Med, Boston, MA USA.
   OBL, BIDMC, Boston, MA USA.
   LMU, UFK, Munich, Germany.
RI Eckstein, Felix/E-1585-2011
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S166
EP S166
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000120
ER

PT J
AU Garner, LW
   Cox, KA
   Hattersley, G
   Rosen, V
AF Garner, LW
   Cox, KA
   Hattersley, G
   Rosen, V
TI Functional analysis of GDF-6/BMP-13 during skeletogenesis.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Genet Inst Inc, Cambridge, MA 02140 USA.
   Millenium Pharmaceut, Cambridge, MA 02140 USA.
   Forsyth Inst, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
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 SEP
PY 2001
VL 16
SU 1
BP S164
EP S164
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000112
ER

PT J
AU Gensure, RC
   Gardella, TJ
   Juppner, H
AF Gensure, RC
   Gardella, TJ
   Juppner, H
TI Bpa at position 28 of PTHrP(1-36) crosslinks to the amino-terminal
   extracellular domain of the PTH/PTHrP receptor and thereby assists in
   predicting a tertiary structure for this receptor region.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Boston, MA USA.
   Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S308
EP S308
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000700
ER

PT J
AU Gori, F
   Demay, MB
AF Gori, F
   Demay, MB
TI Identification of a novel BMP-2 induced gene, which dramatically
   accelerates osteoblast differentiation.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S145
EP S145
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000035
ER

PT J
AU Gouveia, CHA
   Schultz, J
   Brent, GA
AF Gouveia, CHA
   Schultz, J
   Brent, GA
TI Thyroid hormone mediates the activation of vitamin D through the
   induction of 1-alpha hydroxylase in osteoblast-like cells.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Univ Sao Paulo, Dept Hystol, BR-05508 Sao Paulo, Brazil.
   Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
   W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA.
   W Los Angeles VA Med Ctr, Dept Physiol, Los Angeles, CA USA.
   Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S555
EP S555
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001776
ER

PT J
AU Grinspoon, SK
   Warren, MP
   Miller, KK
   Friedman, AJ
   Olson, WH
   Oei, TB
AF Grinspoon, SK
   Warren, MP
   Miller, KK
   Friedman, AJ
   Olson, WH
   Oei, TB
TI Effects of triphasic norgestimate/ethinyl estradiol (NGM/EE) on
   biochemical markers of bone metabolism in women with osteopenia
   secondary to hypothalamic amenorrhea.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Columbia Univ, Dept OB GYN & Med, New York, NY USA.
   Ortho McNeil Pharmaceut, Raritan, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S537
EP S537
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001691
ER

PT J
AU Guo, J
   Chung, U
   Bringhurst, FR
   Kronenberg, HM
AF Guo, J
   Chung, U
   Bringhurst, FR
   Kronenberg, HM
TI Phospholipase C signaling via the PTH/PTHrP receptor is required for
   normal hypertrophic differentiation during endochondral bone formation.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
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 SEP
PY 2001
VL 16
SU 1
BP S228
EP S228
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000374
ER

PT J
AU Huang, W
   Carlsen, B
   Rudkin, G
   Shah, N
   Ishida, K
   Yamaguchi, DT
   Miller, TA
AF Huang, W
   Carlsen, B
   Rudkin, G
   Shah, N
   Ishida, K
   Yamaguchi, DT
   Miller, TA
TI Characterization of senescence-related genes in MC3T3-E1 preosteoblastic
   cells identified by microarray analysis.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 VA Greater LA Healthcare Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S366
EP S366
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000948
ER

PT J
AU Inada, M
   Wang, Y
   Byrne, MH
   Miyaura, C
   Krane, SM
AF Inada, M
   Wang, Y
   Byrne, MH
   Miyaura, C
   Krane, SM
TI Mice with null mutation in collagenase-3 (matrix
   metalloproteinase[MMP]-13) exhibit altered bone remodeling and increased
   bone mass.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Tokyo Univ Pharm & Life Sci, Tokyo, Japan.
NR 0
TC 8
Z9 9
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S149
EP S149
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000053
ER

PT J
AU Jonsson, KB
   Rubin, DA
   Juppner, H
AF Jonsson, KB
   Rubin, DA
   Juppner, H
TI Identification of regions within the type 3 zebrafish PTH-receptor that
   prevent activation of the phospholipase C signaling pathway.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Boston, MA USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC 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 SEP
PY 2001
VL 16
SU 1
BP S549
EP S549
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001749
ER

PT J
AU Jonsson, KB
   Pragnell, M
   Larsson, T
   White, K
   Econs, M
   Schiavi, S
AF Jonsson, KB
   Pragnell, M
   Larsson, T
   White, K
   Econs, M
   Schiavi, S
TI Recombinant FGF-23 interacts in vitro with FGF receptors 2 and 4.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Genzyme, Appl Genom, Framingham, MA USA.
   Indiana Univ, Sch Med, Indianapolis, IN USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S251
EP S251
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000468
ER

PT J
AU Kearns, AE
   Donohue, MM
   Sanyal, B
   Demay, MB
AF Kearns, AE
   Donohue, MM
   Sanyal, B
   Demay, MB
TI Identification of a novel BMP-2 inducible kinase that impairs
   mineralization in vitro.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Mayo Clin, Rochester, MN USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
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 SEP
PY 2001
VL 16
SU 1
BP S373
EP S373
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000980
ER

PT J
AU Kobayashi, T
   McMahon, AP
   Kronenberg, HM
AF Kobayashi, T
   McMahon, AP
   Kronenberg, HM
TI Targeted expression of constitutively active BMP receptor 1A in
   chondrocytes causes lethal skeletal dysplasia with shortening of growth
   plate.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
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 SEP
PY 2001
VL 16
SU 1
BP S142
EP S142
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000023
ER

PT J
AU Kondo, H
   Guo, J
   Chung, U
   Kronenberg, HM
   Bringhurst, FR
AF Kondo, H
   Guo, J
   Chung, U
   Kronenberg, HM
   Bringhurst, FR
TI Roles of PTH/PTHrP receptor generated-signals in RANKL-induced
   osteoclastogenesis.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
NR 0
TC 1
Z9 1
U1 0
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 SEP
PY 2001
VL 16
SU 1
BP S228
EP S228
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000373
ER

PT J
AU Leder, BZ
   Schoenfeld, DA
   LeBlanc, K
   Finkelstein, JS
AF Leder, BZ
   Schoenfeld, DA
   LeBlanc, K
   Finkelstein, JS
TI Both estradiol and testosterone play fundamental roles in the
   maintenance of normal bone turnover in men.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S171
EP S171
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000141
ER

PT J
AU Liu, B
   Wu, P
   Bringhurst, R
   Wang, J
AF Liu, B
   Wu, P
   Bringhurst, R
   Wang, J
TI Estrogen inhibition of parathyroid hormone-stimulated osteoclast
   formation and attachment in vitro: Involvement of both PKA and PKC.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Natl Taiwan Univ, Sch Dent, Taipei, Taiwan.
   Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S508
EP S508
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001565
ER

PT J
AU MacLean, HE
   Cobrinik, D
   Zhang, P
   Kronenberg, HM
AF MacLean, HE
   Cobrinik, D
   Zhang, P
   Kronenberg, HM
TI p57(Kip2), and p107 & p130, regulate chondrocyte proliferation in vivo,
   and may be targets of PTHrP action.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Boston, MA USA.
   Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Columbia Univ, Coll Phys & Surg, New York, NY USA.
   Baylor Coll Med, Houston, TX 77030 USA.
NR 0
TC 0
Z9 0
U1 0
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 SEP
PY 2001
VL 16
SU 1
BP S161
EP S161
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000100
ER

PT J
AU Mahon, MJ
   Donowitz, M
   Segre, GV
AF Mahon, MJ
   Donowitz, M
   Segre, GV
TI Direct binding of the PTH/PTHrP receptor (PTH1R) to the Na-H exchange
   regulatory factor 2 (NHERF2) selectively transfers signaling from
   adenylate cyclase to phospholipase C pathways.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA.
   Johns Hopkins Univ, Dept Gastroenterol, Baltimore, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S159
EP S159
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000091
ER

PT J
AU Ogata, N
   Aikawa, T
   Seki, K
   Tanaka, S
   Segre, GV
   Lee, K
AF Ogata, N
   Aikawa, T
   Seki, K
   Tanaka, S
   Segre, GV
   Lee, K
TI Activation of MEK1 inhibits hypertrophic differentiation of
   chondrocytes.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA.
   Univ Tokyo, Tokyo, Japan.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S324
EP S324
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000764
ER

PT J
AU Patterson, E
   Watson, PH
   Canaff, LE
   Hendy, GN
   Bringhurst, R
   Hodsman, AB
   Fraher, LJ
AF Patterson, E
   Watson, PH
   Canaff, LE
   Hendy, GN
   Bringhurst, R
   Hodsman, AB
   Fraher, LJ
TI Transient expression of GFP-PTH/PTHrP receptor constructs in LLC-PK1
   (clone 46) cells.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Univ Western Ontario, London, ON N6A 3K7, Canada.
   McGill Univ, Calcium Res Lab, Montreal, PQ, Canada.
   Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
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 SEP
PY 2001
VL 16
SU 1
BP S549
EP S549
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001747
ER

PT J
AU Schipani, E
   Ryan, HE
   Kobayashi, T
   Knight, M
   Johnson, RS
AF Schipani, E
   Ryan, HE
   Kobayashi, T
   Knight, M
   Johnson, RS
TI Essential role of HIF-1alpha in growth plate development.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA.
   Univ Calif San Diego, Div Biol, San Diego, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S137
EP S137
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000003
ER

PT J
AU Seki, K
   Aikawa, T
   Ogata, N
   Fujimori, T
   Segre, GV
   Lee, K
AF Seki, K
   Aikawa, T
   Ogata, N
   Fujimori, T
   Segre, GV
   Lee, K
TI Regulation of chondrocyte differentiation by Snail-related
   transcriptional repressors in endochondral bone development.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
   Kyoto Univ, Dept Pathol & Tumor Biol, Kyoto, Japan.
RI Fujimori, Toshihiko/L-7711-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S324
EP S324
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000765
ER

PT J
AU Seton, M
   Sebaldt, R
   Cooper, C
AF Seton, M
   Sebaldt, R
   Cooper, C
TI New England Registry for Paget's disease of bone.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
   McMaster Univ, Hamilton, ON, Canada.
   MRC, Environm Epidemiol Unit, Southampton, Hants, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S302
EP S302
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000676
ER

PT J
AU Shimada, M
   Chen, X
   Cvrk, T
   Hilfiker, H
   Parfenova, M
   Segre, GV
AF Shimada, M
   Chen, X
   Cvrk, T
   Hilfiker, H
   Parfenova, M
   Segre, GV
TI Purification and characterization of solubilized human PTH/PTHrP
   receptors (PTH1R).
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S548
EP S549
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001745
ER

PT J
AU Shimizu, K
   Chen, W
   Liang, Y
   Isoda, R
   Deng, W
   Li, Y
AF Shimizu, K
   Chen, W
   Liang, Y
   Isoda, R
   Deng, W
   Li, Y
TI CNBP enhances bone formation by promoting osteoblast cell proliferation
   and inhibiting osteocalcin expression.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S205
EP S205
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000274
ER

PT J
AU Shimizu, N
   Petroni, BD
   Gardella, TJ
AF Shimizu, N
   Petroni, BD
   Gardella, TJ
TI Functional evidence that the amino acid sidechains at positions 6 and 10
   of PTH interact when the ligand is bound to the PTH-1 receptor.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S546
EP S547
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001735
ER

PT J
AU Shimizu, N
   Guo, J
   Gardella, TJ
AF Shimizu, N
   Guo, J
   Gardella, TJ
TI PTH(1-14) analogs conformationally constrained with
   alpha-aminoisobutyric acid exhibit full potency on the P1R.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S546
EP S546
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001734
ER

PT J
AU Smith, MR
   McGovern, EJ
   Zietman, AL
   Fallon, MA
   Hayden, DL
   Schoenfeld, DA
   Kantoff, PW
   Finkelstein, JS
AF Smith, MR
   McGovern, EJ
   Zietman, AL
   Fallon, MA
   Hayden, DL
   Schoenfeld, DA
   Kantoff, PW
   Finkelstein, JS
TI Pamidronate to prevent bone loss in men receiving gonadotropin-releasing
   hormone agonist therapy for prostate cancer.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER 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 SEP
PY 2001
VL 16
SU 1
BP S147
EP S147
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000044
ER

PT J
AU Solomon, DH
   Finkelstein, JS
   Wang, PS
   Avorn, J
AF Solomon, DH
   Finkelstein, JS
   Wang, PS
   Avorn, J
TI Statin lipid-lowering drugs and bone density.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S293
EP S293
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000637
ER

PT J
AU Solomon, DH
   Connelly, M
   Dawson-Hughes, B
   Rosen, CJ
   Kiel, DP
   Greenspan, SL
   Leib, E
   Miguel, AH
   Finkelstein, JS
AF Solomon, DH
   Connelly, M
   Dawson-Hughes, B
   Rosen, CJ
   Kiel, DP
   Greenspan, SL
   Leib, E
   Miguel, AH
   Finkelstein, JS
TI Why don't primary care physicians screen for osteoporosis?
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Brigham & Womens Hosp, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Tufts Univ, USDA, Nutr Ctr, Boston, MA 02111 USA.
   Maine Ctr Osteoporosis Res, Bangor, ME USA.
   Univ Pittsburgh, Pittsburgh, PA USA.
   Univ Vermont, Burlington, VT USA.
   Procter & Gamble, Cincinnati, OH USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S243
EP S243
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000436
ER

PT J
AU Sooy, K
   Demay, MB
AF Sooy, K
   Demay, MB
TI Transcriptional repression of osteocalcin gene expression by delta EF1.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S176
EP S176
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000159
ER

PT J
AU Tou, L
   Quibria, N
   Alexander, JM
AF Tou, L
   Quibria, N
   Alexander, JM
TI Transcriptional regulation of the cloned human cbfa1 gene promoter by
   bone morphogenetic protein-7.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Boston, MA USA.
   BIDMC, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S321
EP S321
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000752
ER

PT J
AU Vallarta-Ast, NL
   Krueger, DC
   Binkley, NC
AF Vallarta-Ast, NL
   Krueger, DC
   Binkley, NC
TI Densitometric diagnosis of osteoporosis in men: Effect of measurement
   site and normative database.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 William S Middleton Mem Vet Adm Med Ctr, Dept Radiol, Madison, WI 53705 USA.
   Univ Wisconsin, Inst Aging, Madison, WI 53706 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S283
EP S283
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000597
ER

PT J
AU von Stechow, D
   Alexander, JM
   Fish, S
   Chorev, M
   Mueller, R
   Rosenblatt, M
   Illiucci, J
   Wang, Y
   Metcalf, C
   Keenan, T
   Sundaramoorthi, R
   Shakespeare, W
   van Schravendijk, MR
   Dalgamo, D
   Sawyer, T
AF von Stechow, D
   Alexander, JM
   Fish, S
   Chorev, M
   Mueller, R
   Rosenblatt, M
   Illiucci, J
   Wang, Y
   Metcalf, C
   Keenan, T
   Sundaramoorthi, R
   Shakespeare, W
   van Schravendijk, MR
   Dalgamo, D
   Sawyer, T
TI Novel Src tyrosine kinase inhibitors prevent ovariectomy-induced bone
   loss in a Swiss-Webster mouse model of post-menopausal osteoporosis.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA.
   ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S223
EP S223
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000351
ER

PT J
AU Wali, R
   Kong, J
   Demay, MB
   Brasitus, TA
   Bissonnette, M
   Li, YC
AF Wali, R
   Kong, J
   Demay, MB
   Brasitus, TA
   Bissonnette, M
   Li, YC
TI The vitamin D receptor is not required for the rapid activation of PKC
   and rise in intracellular calcium induced by 1,25-dihydroxyvitamin D3 in
   mouse osteoblasts.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Univ Chicago, Chicago, IL 60637 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
NR 0
TC 4
Z9 4
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S229
EP S229
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000379
ER

PT J
AU Wang, Y
   Byrne, MH
   Inada, M
   Rahman, MU
   Krane, SM
AF Wang, Y
   Byrne, MH
   Inada, M
   Rahman, MU
   Krane, SM
TI Null mutation in collagenase-3 (matrix metalloproteinase[MMP]-13)
   affects maturation of growth plates.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S141
EP S141
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000020
ER

PT J
AU Wu, Y
   Chesler, DA
   Ackerman, JL
   Wang, J
   Glimcher, MJ
AF Wu, Y
   Chesler, DA
   Ackerman, JL
   Wang, J
   Glimcher, MJ
TI Solid components of bone matrix measured by proton magnetic resonance
   imaging.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Childrens Hosp, Dept Orthopaed Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S463
EP S463
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709001367
ER

PT J
AU Wu, Y
   Ackerman, JL
   Glimcher, MJ
AF Wu, Y
   Ackerman, JL
   Glimcher, MJ
TI In situ identification of a Ca-organic phosphate complex by 31P solid
   state NMR spectroscopy at onset of mineralization.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Boston, MA USA.
   Childrens Hosp, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S323
EP S323
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000761
ER

PT J
AU Yates, KE
   Glowacki, J
AF Yates, KE
   Glowacki, J
TI Identification and tissue-specific expression of connective tissue genes
   that are upregulated in postnatal chondroinduced human dermal
   fibroblasts.
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Meeting Abstract
C1 Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Charlestown, MA USA.
   Brigham & Womens Hosp, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC BONE & MINERAL RES
PI WASHINGTON
PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA
SN 0884-0431
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD SEP
PY 2001
VL 16
SU 1
BP S238
EP S238
PG 1
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 467MU
UT WOS:000170709000413
ER

PT J
AU Appel, JZ
   Buhler, L
   Cooper, DKC
AF Appel, JZ
   Buhler, L
   Cooper, DKC
TI The pig as a source of cardiac xenograffts
SO JOURNAL OF CARDIAC SURGERY
LA English
DT Review
AB The inadequate availability of human donor hearts and other organs has inspired interest in the field of xenotransplantation. Historically, ten attempts to transplant animal hearts into human recipients have been reported. Those who received hearts from nonhuman primates (i.e., baboons and chimpanzees) survived rather longer than did those who received hearts from nonprimates (i.e., sheep and pigs). Nevertheless, current opinion is that the pig is the best candidate as a source of hearts for humans despite the considerable immunologic disparity between the two species. Pigs are available in large numbers and can be bred easily and rapidly. They grow to appropriate sizes and their cardiovascular system is similar to that of humans. Substantial knowledge has been accumulated regarding both genetic engineering and tolerance induction in pigs, two strategies that may help to overcome the existing immunologic barriers. Concern has been raised, however, with regard to the potential for the transfer of a porcine infection with the pig organ to the human recipient. This brief review addresses these and other aspects of the use of the pig as a source of hearts for patients with end-stage cardiac disease.
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 01129 USA.
   Harvard Univ, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA.
RP Cooper, DKC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 01129 USA.
EM David.Cooper@tbrc.mgh.harvard.edu
NR 84
TC 15
Z9 19
U1 0
U2 2
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 SEP-OCT
PY 2001
VL 16
IS 5
BP 345
EP 356
DI 10.1111/j.1540-8191.2001.tb00534.x
PG 12
WC Cardiac & Cardiovascular Systems; Surgery
SC Cardiovascular System & Cardiology; Surgery
GA V3378
UT WOS:000186228700001
PM 11885765
ER

PT J
AU Fishman, JA
AF Fishman, JA
TI Infection in xenotransplantation
SO JOURNAL OF CARDIAC SURGERY
LA English
DT Article
AB Advances in transplantation immunology have enhanced the possibility of xenotransplantation as a therapeutic option for end-stage organ failure. The potential spread of animal-derived pathogens to the recipient and to the general population, termed "xenosis," is a potential complication of interspecies transplantation. Recognition of such novel infections may be complicated by infections due to altered microbiologic behavior and clinical symptomatology of these organisms, particularly in the immunocompromised xenograft recipient. Particular concern exists over the activation of latent viruses, including retroviruses, from xenograft tissues. Based on experience with human allogeneic transplantation" those pathogens considered most likely to cause human disease can be excluded prospectively from herds of animals developed for organ donation. Research is needed into the activation and behavior of retroviruses and other potential pathogens in xenotransplantation. Xenotransplantation may also provide unique opportunities not only for the care of patients with organ failure, but in the therapy of individuals with chronic infections to which the xenograft may be resistant. Clinical. protocols must be developed so as to enhance the safety of the recipient and of the community-at-large.
C1 Massachusetts Gen Hosp, Div Infect Dis, Infect Dis Unit, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA.
EM jfishman@partners.org
NR 40
TC 25
Z9 25
U1 0
U2 1
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 SEP-OCT
PY 2001
VL 16
IS 5
BP 363
EP 373
DI 10.1111/j.1540-8191.2001.tb00536.x
PG 11
WC Cardiac & Cardiovascular Systems; Surgery
SC Cardiovascular System & Cardiology; Surgery
GA V3378
UT WOS:000186228700003
PM 11885767
ER

PT J
AU Keane, D
AF Keane, D
TI Irrigated radiofrequency catheter ablation
SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY
LA English
DT Editorial Material
ID REENTRY CIRCUIT SITES; VENTRICULAR-TACHYCARDIA; MYOCARDIAL-INFARCTION;
   ELECTRODE SIZE; HEART-DISEASE; LESION SIZE; TIP; ENTRAINMENT; DELIVERY;
   ENERGY
C1 Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Keane, D (reprint author), Massachusetts Gen Hosp, Gray 109,55 Fruit St, Boston, MA 02114 USA.
NR 29
TC 3
Z9 3
U1 0
U2 0
PU FUTURA PUBL CO
PI ARMONK
PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA
SN 1045-3873
J9 J CARDIOVASC ELECTR
JI J. Cardiovasc. Electrophysiol.
PD SEP
PY 2001
VL 12
IS 9
BP 1043
EP 1045
DI 10.1046/j.1540-8167.2001.01043.x
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 470MF
UT WOS:000170875200013
PM 11573695
ER

PT J
AU Frazier, JA
   Biederman, J
   Tohen, M
   Feldman, PD
   Jacobs, TG
   Toma, V
   Rater, MA
   Tarazi, RA
   Kim, GS
   Garfield, SB
   Sohma, M
   Gonzalez-Heydrich, J
   Risser, RC
   Nowlin, ZM
AF Frazier, JA
   Biederman, J
   Tohen, M
   Feldman, PD
   Jacobs, TG
   Toma, V
   Rater, MA
   Tarazi, RA
   Kim, GS
   Garfield, SB
   Sohma, M
   Gonzalez-Heydrich, J
   Risser, RC
   Nowlin, ZM
TI A prospective open-label treatment trial of olanzapine monotherapy in
   children and adolescents with bipolar disorder
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID RATING-SCALE; MOOD DISORDERS; DOUBLE-BLIND; ACUTE MANIA; PLACEBO;
   RELIABILITY; LITHIUM; ONSET; AKATHISIA; VALIDITY
AB Objective: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents.
   Methods: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale).
   Results: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of greater than or equal to 30% decline in the YMRS and a CGI-S Mania score of less than or equal to3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001).
   Conclusions: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.
C1 McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA.
   Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Pediat Psychopharmacol Clin, Boston, MA USA.
   Lilly Res Labs, Indianapolis, IN USA.
   Childrens Hosp, Boston, MA 02115 USA.
RP Frazier, JA (reprint author), McLean Hosp, Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA.
FU NIMH NIH HHS [K08-MH-01573]
NR 37
TC 140
Z9 145
U1 3
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 FAL
PY 2001
VL 11
IS 3
BP 239
EP 250
DI 10.1089/10445460152595568
PG 12
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA 478NF
UT WOS:000171351700004
PM 11642474
ER

PT J
AU Spencer, T
   Biederman, J
   Heiligenstein, J
   Wilens, T
   Faries, D
   Prince, J
   Faraone, SV
   Rea, J
   Witcher, J
   Zervas, S
AF Spencer, T
   Biederman, J
   Heiligenstein, J
   Wilens, T
   Faries, D
   Prince, J
   Faraone, SV
   Rea, J
   Witcher, J
   Zervas, S
TI An open-label, dose-ranging study of atomoxetine in children with
   attention deficit hyperactivity disorder
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID DOPAMINE D4 RECEPTOR; DEFICIT/HYPERACTIVITY DISORDER; STIMULANT
   MEDICATION; CONTROLLED TRIAL; DOUBLE-BLIND; ADHD; METHYLPHENIDATE;
   ADULTS; GENE; DESIPRAMINE
AB Objective: The goal of this study was to evaluate the tolerability and effectiveness of the experimental, noradrenergic specific reuptake inhibitor atomoxetine in the treatment of children with attention deficit hyperactivity disorder (ADHD).
   Methods: This was an open, prospective, dose-ranging study of atomoxetine monotherapy in the treatment of 30 children with ADHD between the ages of 7 and 14 years. Atomoxetine was started at 10-20 mg/day and titrated weekly up to 90 mg over 11 weeks, depending on response and adverse effects. Twenty-two children completed the full 11 weeks. We assessed efficacy with weekly clinician and parent ratings of ADHD and oppositional symptoms and monitored adverse effects, laboratory findings, and cardiovascular parameters.
   Results: Treatment with atomoxetine (mean final, total daily dose of 1.9 mg/kg/day) was very well tolerated without meaningful adverse effects. Atomoxetine significantly reduced core symptoms of ADHD (ADHD-Rating Scale-IV; 38.6% decrease vs. baseline, p < 0.001) with significant improvement (p < 0.05) in all but 1 of the 18 individual items in the ADHD-Rating Scale-IV. More than 75% of subjects who completed 10 weeks of treatment showed > 25% decrease in ADHD symptoms.
   Conclusions: These findings extend to children the positive results previously reported in adults diagnosed with ADHD who were treated with atomoxetine. These results support additional controlled trials of atomoxetine in cases of pediatric ADHD.
C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA.
   Lilly Res Labs, Indianapolis, IN USA.
RP Spencer, T (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC-725,15 Parkman St, Boston, MA 02114 USA.
OI Faraone, Stephen/0000-0002-9217-3982
FU NIMH NIH HHS [R29MH57511]
NR 38
TC 89
Z9 92
U1 3
U2 5
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 FAL
PY 2001
VL 11
IS 3
BP 251
EP 265
DI 10.1089/10445460152595577
PG 15
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA 478NF
UT WOS:000171351700005
PM 11642475
ER

PT J
AU Grinspoon, S
   Corcoran, C
   Stanley, T
   Rabe, J
   Wilkie, S
AF Grinspoon, S
   Corcoran, C
   Stanley, T
   Rabe, J
   Wilkie, S
TI Mechanisms of androgen deficiency in human immunodeficiency
   virus-infected women with the wasting syndrome
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ADRENOCORTICAL FUNCTION; ADRENAL ANDROGEN; MEN; GONADOTROPIN; HEALTHY;
   ILLNESS; BODY; OLD
AB Although prior studies suggest reduced androgen levels in women with acquired immune deficiency syndrome wasting, little is known regarding the regulation of adrenal and ovarian androgen secretion in such patients. We investigated ovarian and adrenal function in 13 human immunodeficiency virus-infected women with acquired immune deficiency syndrome wasting and 21 age- and body mass index-matched healthy control subjects studied in the early follicular phase. Subjects received hCG (5000 U, im) on d 1 and Cosyntropin (0.25 mg, iv) on d 3 after dexamethasone (1 mg, orally, at 2400 h) pretreatment on d 2. At baseline, human immunodeficiency virus-infected subjects demonstrated significantly reduced T [18 +/- 2 vs. 25 +/- 2 ng/dl (0.6 +/- 0.1 vs. 0.9 +/- 0.1 nmol/liter); P = 0.02], free T [1.5 +/- 0.1 vs. 2.4 +/- 0.2 pg/ml (5.3 +/- 0.5 vs. 8.3 +/- 0.6 pmol/liter); P = 0.001], androstenedione [119 +/- 6 vs. 162 +/- 14 ng/dl (4.16 +/- 0.20 vs. 5.66 +/- 0.48 nmol/liter); P = 0.02], and dehydroepiandrosterone sulfate [0.96 +/- 0.17 vs. 1.55 +/- 0.19 mug/ml (2.6 +/- 0.5 vs. 4.2 +/- 0.5 mu mol/liter); P = 0.047) levels compared with the control subjects. T [8 +/- 2 vs. 6 +/- 2 ng/dI (0.3 +/- 0.1 vs. 0.2 +/- 0.1 nmol/liter); P = 0.48], free T [0.5 +/- 0.2 vs. 0.4 +/- 0.1 pg/ml (1.7 +/- 0.7 vs. 1.5 +/- 0.5 pmol/liter); P = 0.85], 17-hydroxyprogesterone [0.5 0.2 vs. 0.7 0.2 mug/liter (1.6 +/- 0.6 vs. 2.0 +/- 0.6 nmol/liter); P = 0.63], and androstenedione [-1 +/- 12 vs. 8 +/- 11 ng/dl (-0.03 +/- 0.42 vs. 0.28 +/- 0.39 nmol/liter), P = 0.61] responses to hCG were not different between the groups. Cortisol responses were increased and dehydroepiandrosterone sulfate responses were decreased in the human immunodeficiency virus-infected vs. control subjects after ACTH stimulation. The ratio of DHEA to cortisol was significantly decreased at 60 (71 +/- 11 vs. 107 +/- 10; P = 0.02) and 90 (63 +/- 8 vs. 102 +/- 9; P = 0.004) min post-ACTH in the human immunodeficiency virus-infected patients compared with control subjects. Baseline urinary free cortisol levels were not different between the groups [36 +/- 9 vs. 36 +/- 5 mug/24 h (99 +/- 26 vs. 100 +/- 13 nmol/d)]. The DHEA to cortisol ratio correlated with the CD4 count (r = 0.67; P = 0.01). These data demonstrate significant shunting of adrenal steroid metabolism away from androgenic pathways and toward cortisol production in human immunodeficiency virus-infected women with the wasting syndrome. In contrast, our data suggest intact ovarian androgen responsivity to hCG stimulation. Further studies of the mechanism of adrenal steroid shunting and the efficacy of androgen replacement in human immunodeficiency virus-infected women are necessary.
C1 Massachusetts Gen Hosp, Neuroendocrinol Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02114 USA.
RP Massachusetts Gen Hosp, Neuroendocrinol Unit, Bulfinch 457B, Boston, MA 02114 USA.
EM sgrinspoon@partners.org
FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [R01-DK-54167, T32-DK-07703]
NR 24
TC 22
Z9 22
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD SEP
PY 2001
VL 86
IS 9
BP 4120
EP 4126
DI 10.1210/jc.86.9.4120
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 471WL
UT WOS:000170951600014
PM 11549636
ER

PT J
AU Fujiwara, T
   Sidis, Y
   Welt, C
   Lambert-Messerlian, G
   Fox, J
   Taylor, A
   Schneyer, A
AF Fujiwara, T
   Sidis, Y
   Welt, C
   Lambert-Messerlian, G
   Fox, J
   Taylor, A
   Schneyer, A
TI Dynamics of inhibin subunit and follistatin mRNA during development of
   normal and polycystic ovary syndrome follicles
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID MESSENGER-RIBONUCLEIC-ACID; ACTIVIN-BINDING PROTEIN; GRANULOSA-LUTEAL
   CELLS; HUMAN MENSTRUAL-CYCLE; FOLLICULAR-FLUID; STIMULATING-HORMONE;
   DIMERIC INHIBIN; IMMUNOHISTOCHEMICAL LOCALIZATION; HEPARAN-SULFATE;
   WOMEN
AB To further explore the developmental dynamics and possible roles of inhibin, activin, and follistatin in the development of human antral follicles as well as the relationship between mRNA and protein levels of these hormones within follicles, quantitative competitive RT-PCR assays were established to determine mRNA levels for the inhibin/activin subunits and both follistatin splice variants. Granulosa cell RNA was obtained by transvaginally aspirating follicles (6-23 mm) from carefully characterized normal women at different times of the follicular phase. alpha- and beta (A)-subunit mRNA levels increased significantly with follicle diameter (r = 0.56; P < 0.01 and r = 0.45; P < 0.05, respectively) and follicle maturity (r = 0.65; P < 0.001 and r = 0.58; P < 0.01, respectively), but beta (B) mRNA levels, which were at least 10-fold lower than levels of the other subunits, showed no relationship to size or maturity. Both follistatin 315 and 288 transcripts were detected in granulosa cells, but neither follistatin transcript varied significantly across the range of follicle sizes analyzed. In addition, granulosa cells contained three follistatin 315 mRNA transcripts for each follistatin 288 transcript, and the follistatin 315/288 ratio did not vary with follicle size. a-Subunit mRNA levels were positively associated with dimeric inhibin A protein in human follicular fluid from the same follicle aspirates (r = 0.71; P < 0.001). Similarly, <beta>(A)-subunit mRNA was associated with inhibin A (r = 0.59; P < 0.01), and <beta>(B) mRNA was associated with inhibin B (r = 0.67; P < 0.005) in these samples. Thus, the increase in inhibin subunit transcription and protein synthesis with follicle size suggests that inhibin biosynthesis might be important for continued development of the dominant follicle.
   To explore this hypothesis further, we compared mRNA levels for each of these transcripts in follicles obtained from six polycystic ovary syndrome patients (eight follicles) and compared the results to those from a group (n = 5) of normal follicles matched for mean diameter. Comparisons were also performed for a subset of polycystic ovary syndrome follicles (n = 5) matched for diameter and size range with the normal group. <alpha>-Subunit mRNA levels were 16-fold lower in both polycystic ovary syndrome follicle groups relative to size-matched normal follicles (P < 0.02), whereas <beta>(A)-subunit mRNA was significantly lower only when all polycystic ovary syndrome follicles were compared. beta (B)-Subunit and follistatin mRNA levels and the follistatin 315/288 ratio were not statistically different for any group. These results suggest that insufficient production of inhibin alpha and possibly beta (A)-subunits, but not follistatin, is associated with follicular arrest in polycystic ovary syndrome follicles.
C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Natl Ctr Infertil Res & Reprod Endocrine Unit, Boston, MA 02114 USA.
   Women & Infants Hosp Rhode Isl, Dept Pathol & Lab Med, Providence, RI 02903 USA.
   Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA.
RP Schneyer, A (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX-5, Boston, MA 02114 USA.
EM schneyer.alan@mgh.harvard.edu
OI Welt, Corrine/0000-0002-8219-5504; Messerlian,
   Geralyn/0000-0002-9440-3411
FU NIDDK NIH HHS [R01-DK-55838]
NR 47
TC 28
Z9 32
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 SEP
PY 2001
VL 86
IS 9
BP 4206
EP 4215
DI 10.1210/jc.86.9.4206
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 471WL
UT WOS:000170951600028
PM 11549651
ER

PT J
AU Palmert, MR
   Hayden, DL
   Mansfield, MJ
   Crigler, JF
   Crowley, WF
   Chandler, DW
   Boepple, PA
AF Palmert, MR
   Hayden, DL
   Mansfield, MJ
   Crigler, JF
   Crowley, WF
   Chandler, DW
   Boepple, PA
TI The longitudinal study of adrenal maturation during gonadal suppression:
   Evidence that adrenarche is a gradual process
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID CENTRAL PRECOCIOUS PUBERTY; DEHYDROEPIANDROSTERONE-SULFATE;
   3-BETA-HYDROXYSTEROID DEHYDROGENASE; DEVELOPMENTAL-CHANGES; PREMATURE
   ADRENARCHE; PREPUBERTAL GIRLS; PLASMA-LEVELS; SEX STEROIDS; ANDROGEN;
   ADRENOCORTICOTROPIN
AB The physical changes that herald the onset of puberty result from the combination of adrenarche and gonadarche. To examine adrenal maturation and associated changes in growth without the confounding effects of changes in the gonadal steroid milieu, we performed a longitudinal study in 14 young girls with idiopathic central precocious puberty during longterm pituitary-gonadal suppression. Beginning at the mean age of 2.9 yr, dehydroepiandrosterone sulfate levels, linear growth, skeletal maturation, body mass index, and secondary sexual development were evaluated at 3- to 6-month intervals for up to 12.3 yr. In 12 of the girls, levels of dehydroepiandrosterone, androstenedione, 17-hydroxypregnenolone, and 17 alpha -hydroxyprogesterone were determined before and after acute ACTH stimulation every 6 months to investigate the maturation of adrenal steroidogenic enzyme activity.
   Serum dehydroepiandrosterone sulfate levels rose progressively throughout the study. An exponential model fit the longitudinal datasets well and indicated that dehydroepiandrosterone sulfate levels increased approximately 22%/yr from the youngest age onward. Increasing activity of 17-20 lyase (CYP17) and decreasing activity of 3 beta -hydroxysteroid dehydrogenase were also evident in preadrenarchal subjects. When controlled for chronological age, no significant associations were noted between weight, body mass index, or body surface area and dehydroepiandrosterone sulfate levels. However, similar analyses revealed modest correlations of both height and growth velocity with dehydroepiandrosterone sulfate levels.
   Our results suggest that adrenarche is not the result of sudden rapid changes in adrenal enzyme activities or adrenal androgen concentrations; rather, adrenarche may be a gradual maturational process that begins in early childhood.
C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA.
   Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA.
   Childrens Hosp, Dept Med, Div Adolescent Med, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Gen Clin Res Ctr, Ctr Biostat, Boston, MA 02114 USA.
   Esoterix Endocrinol Inc, Calabasas Hills, CA 91301 USA.
RP Boepple, PA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 5,Fruit St, Boston, MA 02114 USA.
EM boepple.paul@mgh.harvard.edu
FU NCRR NIH HHS [RR-02172, RR-01066, K23-RR-15544-01]; NICHD NIH HHS
   [HD-18169]
NR 40
TC 81
Z9 86
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 SEP
PY 2001
VL 86
IS 9
BP 4536
EP 4542
DI 10.1210/jc.86.9.4536
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 471WL
UT WOS:000170951600076
PM 11549704
ER

PT J
AU Meigs, JB
   Mohr, B
   Barry, MJ
   Collins, MM
   McKinlay, JB
AF Meigs, JB
   Mohr, B
   Barry, MJ
   Collins, MM
   McKinlay, JB
TI Risk factors for clinical benign prostatic hyperplasia in a
   community-based population of healthy aging men
SO JOURNAL OF CLINICAL EPIDEMIOLOGY
LA English
DT Article; Proceedings Paper
CT 93rd Annual Meeting of the American-Urological-Association
CY MAY 30-JUN 04, 1998
CL SAN DIEGO, CALIFORNIA
SP Amer Urol Assoc
DE benign prostatic hyperplasia; BPH; risk factors; epidemiology; cohort
   studies
ID ACUTE URINARY RETENTION; MIDDLE-AGED MEN; CIGARETTE-SMOKING;
   PHYSICAL-ACTIVITY; NATURAL-HISTORY; HORMONE LEVELS; SEX-HORMONES;
   HYPERTROPHY; DISEASE; ASSOCIATION
AB We defined risk factors for a clinical diagnosis of benign prostatic hyperplasia (BPH) among subjects of the population-based Massachusetts Male Aging Study. In 1987-89 1709 men aged 40-70 provided baseline risk factor data and were followed for a mean of 9 years; 1019 men without prostate cancer provided follow-up data. We classified men with clinical BPH at follow-up if they reported (1) frequent or difficulty urinating and were told by a health professional that they had an enlarged or swollen prostate or (2) if they reported having surgery for BPH. At follow-up the prevalence of clinical BPH was 19.4%, increasing from 8.4% of men aged 38-49 years to 33.5% of men aged 60-70 years (P < 0.001 for trend). Elevated free PSA levels (age- and total PSA-adjusted OR, top vs. bottom quartile ng/mL 4.4, 95% Cl 1.9-10.5). heart disease (age-adjusted OR 2.1, CI 1.3-3.3), and use of beta-blocker medications (OR 1.8, CI 1.1-3.0) increased odds for BPH, while current cigarette smoking (OR 0.5, CI 0.3-0.8) and high levels of physical activity (top vs. bottom quartile kcals/day OR 0.5, CI 0.3-0.9) decreased odds of BPH. All but the medication effects persisted in fully adjusted multivariable models. Total or fat calorie intake, sexual activity level, alcohol intake, body mass index, waist-hip ratio, diastolic blood pressure, a history of diabetes, hypertension, vasectomy, or serum levels of androgens or estrogens did not individually predict clinical BPH. We conclude that physical exercise and cigarette smoking appear to protect against development of clinical BPH. Elevated free PSA levels predict clinical BPH independent of total PSA levels. Risk associated with heart disease does not appear to be due solely to detection bias or to effects of heart disease medications. A wide variety of other characteristics appear to have no influence on risk for clinical BPH. (C) 2001 Elsevier Science Inc. All rights reserved.
C1 Massachusetts Gen Hosp, Med Serv, Gen Med Unit, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA 02114 USA.
   New England Res Inst, Watertown, MA 02172 USA.
RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Med Serv, Gen Med Unit, 50 Staniford St, Boston, MA 02114 USA.
FU AHRQ HHS [HS 08397]; NIA NIH HHS [AG 04673]; NIDDK NIH HHS [DK 44995, DK
   51345]
NR 35
TC 201
Z9 222
U1 0
U2 6
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 SEP
PY 2001
VL 54
IS 9
BP 935
EP 944
DI 10.1016/S0895-4356(01)00351-1
PG 10
WC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
   Health
GA 465RE
UT WOS:000170603100011
PM 11520654
ER

PT J
AU Reddick, BH
   Catlin, E
   Jellinek, M
AF Reddick, BH
   Catlin, E
   Jellinek, M
TI Crisis within crisis: Recommendations for defining, preventing, and
   coping with stressors in the NICU
SO JOURNAL OF CLINICAL ETHICS
LA English
DT Article
ID INTENSIVE-CARE UNIT; HOUSE STAFF; DEATH; GRIEF
C1 Massachusetts Gen Hosp, Dept Child & Adolescent Psychol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Neonatol, Cambridge, MA 02138 USA.
   Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA.
NR 23
TC 4
Z9 4
U1 0
U2 2
PU UNIV PUBLISHING GROUP
PI HAGERSTOWN
PA 17100 COLE RD #312, HAGERSTOWN, MD 21740-6901 USA
SN 1046-7890
J9 J CLIN ETHIC
JI J. Clin. Ethics
PD FAL
PY 2001
VL 12
IS 3
BP 254
EP 265
PG 12
WC Ethics; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Biomedical Social Sciences
GA 506JL
UT WOS:000172966600009
PM 11789069
ER

PT J
AU Opitz, OG
   Suliman, Y
   Hahn, WC
   Harada, H
   Blum, HE
   Rustgi, AK
AF Opitz, OG
   Suliman, Y
   Hahn, WC
   Harada, H
   Blum, HE
   Rustgi, AK
TI Cyclin D1 overexpression and p53 inactivation immortalize primary oral
   keratinocytes by a telomerase-independent mechanism
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID SQUAMOUS-CELL CARCINOMA; HUMAN-DIPLOID FIBROBLASTS; LIFE-SPAN; LACKING
   TELOMERASE; HUMAN CANCER; EXPRESSION; SENESCENCE; LENGTH; MICE; GENE
AB The immortalization of human cells is a critical step in multistep carcinogenesis. Oral-esophageal carcinomas, a model system to investigate molecular mechanisms underlying squamous carcinogenesis, frequently involve cyclin D1 overexpression and inactivation of the p53 tumor suppressor. Therefore, our goal was to establish the functional role of cyclin D I overexpression and p53 inactivation in the immortalization of primary human oral squamous epithelial cells (keratinocytes) as an important step toward malignant transformation. Cyclin D I overexpression alone was found to induce extension of the replicative life span of normal oral keratinocytes, whereas the combination of cyclin DI overexpression and p53 inactivation led to their immortalization. This study also demonstrates that immortalization of oral keratinocytes can be independent of telomerase activation, involving an alternative pathway of telomere maintenance (ALT).
C1 Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA.
   Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA USA.
   Univ Freiburg, Dept Med, D-7800 Freiburg, Germany.
   Whitehead Inst Biomed Res, Cambridge, MA 02142 USA.
   Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA.
   Univ Penn, Dept Genet, Philadelphia, PA 19104 USA.
RP Rustgi, AK (reprint author), Univ Penn, Div Gastroenterol, 600A CRB,415 Curie Blvd, Philadelphia, PA 19104 USA.
FU NIDCR NIH HHS [P01-DE12467, P01 DE012467]; NIDDK NIH HHS [R01-DK53377]
NR 50
TC 51
Z9 58
U1 1
U2 4
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2001
VL 108
IS 5
BP 725
EP 732
DI 10.1172/JCI11909
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 469MF
UT WOS:000170818900014
PM 11544278
ER

PT J
AU Manjunath, N
   Shankar, P
   Wan, J
   Weninger, W
   Crowley, MA
   Hieshima, K
   Springer, TA
   Fan, X
   Shen, H
   Lieberman, J
   von Andrian, UH
AF Manjunath, N
   Shankar, P
   Wan, J
   Weninger, W
   Crowley, MA
   Hieshima, K
   Springer, TA
   Fan, X
   Shen, H
   Lieberman, J
   von Andrian, UH
TI Effector differentiation is not prerequisite for generation of memory
   cytotoxic T lymphocytes
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID IN-VIVO; VIRAL-INFECTION; VIRUS-INFECTION; IMMUNOLOGICAL MEMORY;
   CELL-DIFFERENTIATION; PROTECTIVE IMMUNITY; APOPTOSIS; HOMEOSTASIS;
   EXPRESSION; ANTIGEN
AB The lineage relationship between short-lived effector T cells and long-lived memory cells is not fully understood. We have described T-GFP mice previously, in which naive and early activated T cells express GFP uniformly, whereas cells that have differentiated into effector cytotoxic T cells selectively lose GFP expression. Here we studied antigen-specific CD8 T cell differentiation using T GFP mice crossed to the TCR transgenic (Tg) mice P14 (specific for the lymphocytic choriomeningitis virus glycoprotein peptide, gp33-41). After activation with antigenic peptide, P14XT-GFP CD8(+) T cells cultured in high-dose IL-2 developed into cells with effector phenotype and function: they were blastoid, lost GFP expression, expressed high levels of activation and effector markers, and were capable of immediate cytotoxic function. In contrast, cells cultured in IL-15 or low-dose IL-2 never developed into full-fledged effector cells. Rather, they resembled memory cells: they were smaller, were GFP(+), did not express effector markers, and were incapable of immediate cytotoxicity. However, they mediated rapid-recall responses in vitro. After adoptive transfer, they survived in vivo for at least 10 weeks and mounted a secondary immune response after antigen rechallenge that was as potent as endogenously generated memory cells. In addition to providing a simple means to generate memory cells in virtually unlimited numbers, our results suggest that effector differentiation is not a prerequisite for memory cell generation.
C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
   Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA.
RP Manjunath, N (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA.
RI von Andrian, Ulrich/A-5775-2008; Lieberman, Judy/A-2717-2015
FU NHLBI NIH HHS [HL-54936, HL-56949, P01 HL056949, R01 HL054936]; NIAID
   NIH HHS [AI-45025, AI-45406, AI-46566, AI-5911, R01 AI045025, R01
   AI045406, R01 AI046566, R21 AI046566]
NR 44
TC 302
Z9 309
U1 2
U2 9
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD SEP
PY 2001
VL 108
IS 6
BP 871
EP 878
DI 10.1172/JCI13296
PG 8
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 473LB
UT WOS:000171044500014
PM 11560956
ER

PT J
AU Flannery, B
   Costa, D
   Carvalho, FP
   Guerreiro, H
   Matsunaga, J
   Da Silva, ED
   Ferreira, AGP
   Riley, LW
   Reis, MG
   Haake, DA
   Ko, AI
AF Flannery, B
   Costa, D
   Carvalho, FP
   Guerreiro, H
   Matsunaga, J
   Da Silva, ED
   Ferreira, AGP
   Riley, LW
   Reis, MG
   Haake, DA
   Ko, AI
TI Evaluation of recombinant Leptospira antigen-based enzyme-linked
   immunosorbent assays for the serodiagnosis of leptospirosis
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID INTERNATIONAL MULTICENTER EVALUATION; OUTER-MEMBRANE PROTEIN; HUMAN
   IMMUNE-RESPONSE; IMMUNOGLOBULIN-M; DIPSTICK ASSAY; PATHOGENIC
   LEPTOSPIRA; PULMONARY HEMORRHAGE; MAMMALIAN INFECTION;
   MOLECULAR-CLONING; SEQUENCE-ANALYSIS
AB There is an urgent need for development of new serodiagnostic strategies for leptospirosis, an emerging zoonosis with worldwide distribution. We have evaluated the diagnostic utility of five recombinant antigens in enzyme-linked immunosorbent assays (ELISAs) for serodiagnosis of leptospirosis. Sera from 50 healthy residents of a high-incidence region were used to determine cutoff values for 96% specificity. In paired sera from 50 cases of leptospirosis confirmed by the microscopic agglutination test, immunoglobulin G (IgG) but not IgM reacted with the recombinant leptospiral proteins. The recombinant LipL32 IgG ELISA had the highest sensitivities in the acute (56%) and convalescent (94%) phases of leptospirosis. ELISAs based on recombinant OmpL1, LipL41, and Hsp58 had sensitivities of 16, 24, and 18% during the acute phase and 72, 44, and 32% during convalescence, respectively. Compared to sera from healthy individuals, patient sera did not react significantly with recombinant LipL36 (P > 0.05). Recombinant LipL32 IgG ELISA demonstrated 95% specificity among 100 healthy individuals, and specificities ranging from 90 to 97% among 30 dengue patients, 30 hepatitis patients, and 16 patients with diseases initially thought to be leptospirosis. Among 39 Venereal Disease Research Laboratory test-positive individuals and 30 Lyme disease patients, 13 and 23% of sera, respectively, reacted positively with the rLipL32 antigen. These findings indicate that rLipL32 may be an useful antigen for the serodiagnosis of leptospirosis.
C1 Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, BR-40295001 Salvador, BA, Brazil.
   Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
   Univ Fed Bahia, Sch Pharm, Salvador, BA, Brazil.
   Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA.
   Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA.
   Brazilian Minist HLth, Oswaldo Cruz Fdn, Rio De Janeiro, Brazil.
   Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, New York, NY 10021 USA.
RP Ko, AI (reprint author), Minist Hlth, Oswaldo Cruz Fdn, Goncalo Moniz Res Ctr, Rua Waldemar Falcao 121, BR-40295001 Salvador, BA, Brazil.
RI Ko, Albert/P-2343-2015
FU FIC NIH HHS [D43 TW000905, D43 TW000919, TW-00905, TW-00919]; NIAID NIH
   HHS [AI-01605, AI-34431, R01 AI034431, R21 AI034431, R21 AI034431-06,
   R29 AI034431]
NR 51
TC 108
Z9 122
U1 1
U2 8
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 SEP
PY 2001
VL 39
IS 9
BP 3303
EP 3310
DI 10.1128/JCM.39.9.3303-3310.2001
PG 8
WC Microbiology
SC Microbiology
GA 469VV
UT WOS:000170837500045
PM 11526167
ER

PT J
AU Stewart, AK
   Vescio, R
   Schiller, G
   Ballester, O
   Noga, S
   Rugo, H
   Freytes, C
   Stadtmauer, E
   Tarantolo, S
   Sahebi, F
   Stiff, P
   Meharchard, J
   Schlossman, R
   Brown, R
   Tully, H
   Benyunes, M
   Jacobs, C
   Berenson, R
   White, M
   DiPersio, J
   Anderson, KC
   Berenson, J
AF Stewart, AK
   Vescio, R
   Schiller, G
   Ballester, O
   Noga, S
   Rugo, H
   Freytes, C
   Stadtmauer, E
   Tarantolo, S
   Sahebi, F
   Stiff, P
   Meharchard, J
   Schlossman, R
   Brown, R
   Tully, H
   Benyunes, M
   Jacobs, C
   Berenson, R
   White, M
   DiPersio, J
   Anderson, KC
   Berenson, J
TI Purging of autologous peripheral-blood stem cells using CD34 selection
   does not improve overall or progression-free survival after high-dose
   chemotherapy for multiple myeloma: Results of a multicenter randomized
   controlled trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; CIRCULATING CLONAL CELLS; PLASMA-CELLS;
   BREAST-CANCER; HEMATOPOIETIC PROGENITORS; POSITIVE SELECTION;
   MESSENGER-RNA; THERAPY; RELAPSE; ENGRAFTMENT
AB Purpose: Although high-dose chemotherapy supported by autologous peripheral-blood progenitor-cell (PBPC) transplantation improves response rates and survival for patients with multiple myeloma, all patients eventually develop progressive disease after transplantation. It has been hypothesized that depletion of malignant plasma cells from autografts may improve outcome by reducing infused cells contributing to relapse.
   Patients and Methods: A randomized phase III study using the CEPRATE SC System (Cellpro, Bothell, WA) to enrich CD34(+) autograft cells and passively purge malignant plasma cells was completed in 190 myeloma patients randomized to receive an autograft of CD34-selected or unselected PBPCs.
   Results: After CD34 selection, tumor burden was reduced by 1.6 to 6.0 logs (median, 3.1), with 54% of CD34-enriched products having no detectable tumor. Median time to count recovery, number of transfusions, transplantation-related mortality, and days in hospital were equivalent between the two transplantation arms. With a median follow-up of 37 months, 33 patients (36%) in the selected and 34 patients (35%) in the unselected arm had died (P = .784). Median overall survival in the selected arm was reached at 50 months and is not reached at this time in the unselected arm (P = .78). Median disease-free survival was 100 versus 104 weeks (P = .82), with 67% of patients in the selected arm and 66% of patients in the unselected arm relapsing.
   Conclusion: This phase III trial demonstrates that although CD34 selection significantly reduces myeloma cell contamination in PBPC collections, no improvement in disease-free or overall survival was achieved.
C1 Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada.
   Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA.
   CellPro Inc, Bothell, WA USA.
   Dana Farber Canc Inst, Boston, MA 02115 USA.
   Dana Farber Canc Inst, St Louis, MO USA.
   Washington Univ, Sch Med, St Louis, MO USA.
   Loyola Univ, Chicago, IL 60611 USA.
   Univ Nebraska, Omaha, NE 68182 USA.
   Univ Penn, Philadelphia, PA 19104 USA.
   Univ Texas San Antonio, San Antonio, TX 78285 USA.
   Johns Hopkins Univ, Baltimore, MD USA.
   Univ S Florida, Miami, FL USA.
   Univ Calif San Francisco, San Francisco, CA 94143 USA.
   So Calif Kaiser Permanente Med Grp, Los Angeles, CA USA.
RP Stewart, AK (reprint author), Princess Margaret Hosp, 610 Univ Ave,Rm 5-126, Toronto, ON M5G 2M9, Canada.
EM k.stewart@uhnres.utoronto.ca
NR 33
TC 127
Z9 130
U1 0
U2 0
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD SEP 1
PY 2001
VL 19
IS 17
BP 3771
EP 3779
PG 9
WC Oncology
SC Oncology
GA 467WW
UT WOS:000170727600011
PM 11533101
ER

PT J
AU Alpert, NM
   Berdichevsky, D
   Levin, Z
   Thangaraj, V
   Gonzalez, G
   Lev, MH
AF Alpert, NM
   Berdichevsky, D
   Levin, Z
   Thangaraj, V
   Gonzalez, G
   Lev, MH
TI Performance evaluation of an automated system for registration and
   postprocessing of CT scans
SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
LA English
DT Article
DE computed tomography; computed tomography, techniques; computed
   tomography, angiography
ID IMAGE REGISTRATION; MR-IMAGES; BRAIN; PET; ALGORITHM; ACCURACY
AB A prototype system optimized for automatic registration of CT scans and applications such as subtraction enhancement and CT angiography was evaluated. Co-registration was performed on 50 studies of various types, including CT angiograms. Mean registration speed was 109 s; accuracy was 2.0 mm. Examples of subtraction enhancement and automatic extraction of the vascular tree are provided. Unattended registration was demonstrated in routine application. Subtraction-enhanced images and extraction of the vascular tree may be useful in clinical practice.
C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA.
   Integrated Med Imaging Syst Inc, Watertown, MA USA.
RP Alpert, NM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Fruit St, Boston, MA 02114 USA.
NR 15
TC 11
Z9 11
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 SEP-OCT
PY 2001
VL 25
IS 5
BP 747
EP 752
DI 10.1097/00004728-200109000-00013
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 473MH
UT WOS:000171047700013
PM 11584235
ER

PT J
AU Harisinghani, MG
   Saini, S
   Weissleder, R
   Rubin, D
   deLange, E
   Harms, S
   Weinreb, J
   Small, W
   Sukerkar, A
   Brown, JJ
   Zelch, J
   Lucas, M
   Morris, M
   Hahn, PF
AF Harisinghani, MG
   Saini, S
   Weissleder, R
   Rubin, D
   deLange, E
   Harms, S
   Weinreb, J
   Small, W
   Sukerkar, A
   Brown, JJ
   Zelch, J
   Lucas, M
   Morris, M
   Hahn, PF
TI Splenic imaging with ultrasmall superparamagnetic iron oxide
   ferumoxtran-10 (AMI-7227): Preliminary observations
SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY
LA English
DT Article
DE magnetic resonance imaging; spleen; contrast agents; ferumoxtran-10
ID CONTRAST AGENTS; ENHANCEMENT PATTERNS; MR-IMAGES; SPLEEN; LIVER;
   LESIONS; EXPERIENCE; METASTASES; TUMORS; RATS
AB Purpose: Ferumoxtran-10 (ultrasmall superparamagnetic iron oxide: Combidex. AMI-7227) is a long-circulating MR contrast agent with reticuloendothelial uptake known to enhance tissue TI and T2 relaxation rates. The purpose of this study was to assess the effect of ferumoxtran-10-enhanced MRI in evaluating focal splenic lesions.
   Method: Eighteen patients underwent MR evaluation of the spleen. Two of these patients with exophytic normal splenic tissue (splenules) and 13 of these patients with 24 focal splenic lesions (7 cysts. 2 hemangiomas, 7 metastases, I infarct, 7 lymphoma) were assessed by T1-weighted gradient echo and T2-weighted fast SE MRI following intravenous administration of ferumoxtran-10 (1.1 mg of Fe/kg). Qualitative analysis involving improved lesion detection and/or characterization. additional information from postcontrast images affecting staging, and patient management was performed. Quantitative measurements of lesion-to-spleen contrast-to-noise ratio were also performed.
   Results: Additional information was provided by ferumoxtran-10-enhanced images in 15 of 18 patients. In 8 of 15 (53%) patients, improved lesion detection (i.e,, number of lesions) was obtained on contrast-enhanced images. Improved lesion visualization (i.e.. conspicuity) was noted in I I of 15 (73%) of patients. In 10 of 15 (67%) patients, postcontrast imaging provided additional information leading to lesion characterization. Staging of disease and patient management were affected in 5 of 15 (33%) and 6 of 15 (40%) patients. respectively.
   Conclusion: Ferumoxtran-10 is a promising contrast agent for the evaluation of focal splenic lesions.
C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Good Samaritan Hosp, San Jose, CA USA.
   Univ Virginia, Hlth Sci Ctr, Lee St & New Hosp, Charlottesville, VA USA.
   Univ Arkansas, Little Rock, AR 72204 USA.
   NYU Med Ctr, New York, NY 10016 USA.
   Emory Univ Hosp, Atlanta, GA 30322 USA.
   Illinois Masonic Med Ctr, Chicago, IL 60657 USA.
   Washington Univ, Med Ctr, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
   Reg MRI Mentor, Mentor, OH USA.
   Adv Magnet Inc, Princeton, NJ USA.
RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, White 270, Boston, MA 02114 USA.
NR 29
TC 15
Z9 17
U1 0
U2 2
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 SEP-OCT
PY 2001
VL 25
IS 5
BP 770
EP 776
DI 10.1097/00004728-200109000-00017
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 473MH
UT WOS:000171047700017
PM 11584239
ER

PT J
AU Gao, XJ
   Fan, Y
   Kent, RL
   Van Houte, J
   Margolis, HC
AF Gao, XJ
   Fan, Y
   Kent, RL
   Van Houte, J
   Margolis, HC
TI Association of caries activity with the composition of dental plaque
   fluid
SO JOURNAL OF DENTAL RESEARCH
LA English
DT Article
DE dental plaque fluid; dental caries; enamel demineralization
ID DEMINERALIZATION IN-VITRO; ENAMEL DEMINERALIZATION; CALCIUM; PH;
   SUCROSE; SALIVA; SATURATION; PHOSPHATE; KINETICS; BACTERIA
AB This study tests the hypothesis that caries activity is associated with lower degrees of saturation with respect to enamel mineral in dental plaque fluid following sucrose exposure. Plaque fluids were obtained from caries-free, caries-positive, and caries-active subjects. Samples were collected before and at 3 and 7 min after a sucrose rinse on consecutive weeks and analyzed for organic acids, inorganic ions, pH, calcium activity, and, in selected samples, total protein. After sucrose, pH values were significantly lower in the caries-active group in comparison with the caries-free and caries-positive groups. Total and free calcium concentrations increased with decreasing pH, with free calcium being about one-third of total calcium. The caries-active group exhibited significantly lower degrees of saturation with respect to enamel mineral, after sucrose, and had significantly higher mutans streptococci levels in plaque than did the caries-free samples. Thus, saturation levels in post-sucrose plaque fluids reflect the cariogenic potential of dental plaque.
C1 Forsyth Inst, Boston, MA 02115 USA.
RP Margolis, HC (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA.
FU NIDCR NIH HHS [DE-07493]
NR 27
TC 30
Z9 35
U1 0
U2 4
PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R
PI ALEXANDRIA
PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA
SN 0022-0345
J9 J DENT RES
JI J. Dent. Res.
PD SEP
PY 2001
VL 80
IS 9
BP 1834
EP 1839
PG 6
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 536CX
UT WOS:000174684100012
PM 11926243
ER

PT J
AU Boyko, EJ
   Ahroni, JH
   Stensel, VL
AF Boyko, EJ
   Ahroni, JH
   Stensel, VL
TI Skin temperature in the neuropathic diabetic foot
SO JOURNAL OF DIABETES AND ITS COMPLICATIONS
LA English
DT Article
DE diabetic foot; peripheral neuropathy; skin temperature; autonomic
   neuropathy
ID BLOOD-FLOW; MELLITUS; RISK
AB Several authors have reported higher skin temperature in the feet of diabetic subjects with autonomic neuropathy. We reexamined this association in a cross-sectional study of 712 veterans with diabetes mellitus. Potential subjects included all diabetic patients enrolled in a general internal medicine clinic at a veterans affairs healthcare system. Sensory neuropathy was defined as any pedal insensitivity to the 5.07 monofilament. Autonomic neuropathy was determined using standard cardiovascular reflex tests. An infrared surface scanner was used to measure foot skin temperature at multiple sites. Subjects with sensory neuropathy had lower mean plantar foot skill temperature than those without (28.4 degreesC vs. 28.9 degreesC, P=.0101). Autonomic neuropathy as a dichotomous variable was unrelated to foot skill temperature. Foot skill temperature, though, negatively correlated with greater drop in systolic blood pressure with standing, which is an indicator of autonomic neuropathy (r=-.08, P=.0385). Adjustment for potential confounding factors using multiple linear regression analysis resulted in diminution of the associations between foot skin temperature and sensory neuropathy or orthostatic blood pressure drop, but the latter association remained statistically significant in the right foot. Diabetic veterans with sensory or autonomic neuropathy do not have higher foot skin temperature. Our results suggest that skin temperature may be slightly lower with higher orthostatic blood pressure fall. Other causes exist for the frequently observed differences in skill temperature in the feet of diabetic subjects. (C) 2001 Elsevier Science Inc. All rights reserved.
C1 Vet Affairs Puget Sound Hlth Care Syst, Gen Internal Med Sect, Seattle, WA 98108 USA.
   Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA.
   Univ Washington, Dept Med, Seattle, WA USA.
   Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA.
   Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Clin Fac, Seattle, WA 98195 USA.
RP Boyko, EJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Gen Internal Med Sect, 1660 S Columbian Way, Seattle, WA 98108 USA.
NR 16
TC 14
Z9 14
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA
SN 1056-8727
J9 J DIABETES COMPLICAT
JI J. Diabetes Complications
PD SEP-OCT
PY 2001
VL 15
IS 5
BP 260
EP 264
DI 10.1016/S1056-8727(01)00156-8
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 468VL
UT WOS:000170778800007
PM 11522501
ER

PT J
AU Gouveia, CH
   Schultz, JJ
   Bianco, AC
   Brent, GA
AF Gouveia, CH
   Schultz, JJ
   Bianco, AC
   Brent, GA
TI Thyroid hormone stimulation of osteocalcin gene expression in ROS 17/2.8
   cells is mediated by transcriptional and post-transcriptional mechanisms
SO JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID RAT OSTEOBLASTIC CELLS; VITAMIN-D-RECEPTOR; MESSENGER-RNA; DEFICIENT
   MICE; 1,25-DIHYDROXYVITAMIN D-3; POSTNATAL-DEVELOPMENT; RESPONSE
   ELEMENT; BONE-RESORPTION; DIFFERENTIATION; TRANSACTIVATION
AB We investigated the mechanism of thyroid hormone regulation of osteocalcin (OC) gene expression in osteoblast-like cells (ROS 17/2.8). Treatment with triiodothyronine (T-3) (10(-8) M) increased OC mRNA levels by similar to3-fold after 24h and reached a maximum, similar to5.4-fold, after 48 h. The mRNA levels of other bone-specific genes, alkaline phosphatase and osteopontin, were not affected by T-3 treatment. Interestingly, T3 induction of OC mRNA varied according to cell density: similar to4-fold at similar to1 x 10(5) cells/dish and 1.5-fold at 40-60 x 10(5) cells/ dish. The magnitude of OC mRNA induction by T-3 was similar to 40% lower than induction by 1,25 dihydroxyvitamin D-3 (1,25D(3)) alone, and the combination of T-3 + 1,25D(3) did not further stimulate OC mRNA levels. T-3 induction of OC mRNA was not affected by treatment with cycloheximide (10 mug/ml) for 5 li indicating that new protein synthesis is not required for the response. To study the half-life of OC mRNA, ROS 17/2.8 cells were incubated with actinomycin D. The basal half-life of OC mRNA (means +/- S.E.M.) was 6.4 +/- 0.2 h which was increased significantly with either T-3 or 1,25D(3) treatment to 10.9 +/- 0.6 h and 13.5 +/- 0.4 h respectively. T3 modestly up-regulated the rate of OC gene transcription (1.7 +/- 0.2fold) as determined by run-off assay. T3 did not induce a reporter construct containing the rat OC gene (rOC) 5'-flanking region (to -1750 bp) or the previously described rOC vitamn D response element, when transfected into ROS 17/2.8 cells. In conclusion, T3 up-regulates the OC mRNA expression in ROS 17/2.8 cells in a dose-, time- and cell confluence-dependent fashion, and does so by transcriptional and posttranscriptional mechanisms. The greater T3 induction of OC expression in ROS 17/2.8 cells at low cell density is consistent with findings of thyroid hormone action on bone development.
C1 VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Los Angeles, CA 90073 USA.
   Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA.
   Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA.
   Univ Sao Paulo, Dept Physiol, Sao Paulo, Brazil.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thyroid, Boston, MA 02115 USA.
RP Brent, GA (reprint author), VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
RI Bianco, Antonio/A-4965-2008
OI Bianco, Antonio/0000-0001-7737-6813
FU NIDDK NIH HHS [DK 43714]
NR 50
TC 37
Z9 40
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 SEP
PY 2001
VL 170
IS 3
BP 667
EP 675
DI 10.1677/joe.0.1700667
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 472PB
UT WOS:000170991700020
PM 11524248
ER

PT J
AU Kim, B
   Lyons, TM
   Parada, JP
   Uphold, DR
   Yarnold, PR
   Hounshell, JB
   Sipler, AM
   Goetz, MB
   DeHovitz, JA
   Weinstein, RA
   Campo, RE
   Bennett, CL
AF Kim, B
   Lyons, TM
   Parada, JP
   Uphold, DR
   Yarnold, PR
   Hounshell, JB
   Sipler, AM
   Goetz, MB
   DeHovitz, JA
   Weinstein, RA
   Campo, RE
   Bennett, CL
TI HIV-related Pneumocystis carinii pneumonia in older patients
   hospitalized in the early HAART era
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE HIV; Pneumocystis carinii pneumonia; age; quality of care; outcomes
ID IMMUNODEFICIENCY-VIRUS INFECTION; AIDS; CARE; MORTALITY; ADULTS
AB OBJECTIVE: To determine whether older age continues to Influence patterns of care and in-hospital mortality for hospitalized persons with BW-related Pneumocystis carinii pneumonia (PCP), as determined In our prior study from the 1980s.
   DESIGN. Retrospective chart review.
   PATIENTS/SETTING: Patients (1,861) with HIV-related PCP at 78 hospitals In 8 cities from 1995 to 1997.
   MEASUREMENTS: Medical record notation of possible HIV infection; alveolar-arterial oxygen gradient; CD4 lymphocyte count; presence or absence of wasting; timely use of anti-PCP medications; In-hospital mortality.
   MAIN RESULTS: Compared to younger patients, patients greater than or equal to 50 years of age were less likely to have HIV mentioned in their progress notes (70% vs 82%, P <.001), have mild or moderately severe PCP cases at admission (89% vs 96%, P <.002), receive anti-PCP medications within the first 2 days of hospitalization (86% vs 93%, P <.002), and survive hospitalization (82% vs 90%, P <.003). However, age was not a significant predictor of mortality after adjustment for severity of PCP and timeliness of therapy.
   CONCLUSIONS: While inpatient PCP mortality has Improved by 50% In the past decade, 2-fold age-related mortality differences persist. As in the 1980s, these differences are associated with lower rates of recognition of HIV, Increased severity of illness at admission, and delays in initiation of PCP-specific treatments among older individuals - factors suggestive of delayed recognition of HIV infection, pneumonia, and PCP, respectively. Continued vigilance for the possibility of HIV and HIV-related PCP among persons greater than or equal to 50 years of age who present with new pulmonary symptoms should be encouraged.
C1 VA Chicago Hlth Care Syst, Lakeside Div, Chicago, IL 60611 USA.
   Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA.
   Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA.
   US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midw Ctr Hlth Serv Res & Policy, Hines, IL 60141 USA.
   Malcolm Randall VA Med Ctr, Brain Rehabil Res Ctr, Gainesville, FL USA.
   VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA.
   Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
   SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA.
   Cook Cty Hosp, Dept Med, Chicago, IL 60612 USA.
   Rush Med Coll, Chicago, IL 60612 USA.
   Univ Miami, Sch Med, Div Infect Dis, Miami, FL USA.
RP Bennett, CL (reprint author), VA Chicago Hlth Care Syst, Lakeside Div, 400 E Ontario St,Suite 205, Chicago, IL 60611 USA.
OI Goetz, Matthew/0000-0003-4542-992X
FU NIDA NIH HHS [5R01DA10628-02]
NR 23
TC 8
Z9 8
U1 0
U2 0
PU BLACKWELL SCIENCE INC
PI MALDEN
PA 350 MAIN ST, MALDEN, MA 02148 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD SEP
PY 2001
VL 16
IS 9
BP 583
EP 589
DI 10.1046/j.1525-1497.2001.016009583.x
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 475TV
UT WOS:000171184700002
PM 11556938
ER

PT J
AU Levin, KP
   Hanusa, BH
   Rotondi, A
   Singer, DE
   Coley, CM
   Marrie, TJ
   Kapoor, WN
   Fine, MJ
AF Levin, KP
   Hanusa, BH
   Rotondi, A
   Singer, DE
   Coley, CM
   Marrie, TJ
   Kapoor, WN
   Fine, MJ
TI Arterial blood gas and pulse oximetry in initial management of patients
   with community-acquired pneumonia
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE community-acquired pneumonia; hypoxemia; blood gas analysis; oximetry
ID RELIABILITY; OUTCOMES; COHORT; CARE
AB OBJECTIVE: To identify the factors associated with the use of arterial blood gas (ABG) and pulse oximetry (PO) In the initial management of patients with community-acquired pneumonia (CAP) and arterial hypoxemia at presentation.
   PARTICIPANTS: A total of 944 outpatients and 1,332 inpatients with clinical and radiographic evidence of CAP prospectively enrolled from 5 study sites in the United States and Canada. ANALYSES: Separate multivariate logistic regression analyses were used to 1) compare measurement of ABG and PO within 48 hours of presentation across sites while controlling for patient differences, and 2) Identify factors associated with arterial hypoxemia (PaO2 <60 MM Hg Or SaO(2) <90% for non - African Americans and <92% for African Americans) while breathing room air.
   RESULTS: Range of ABG use by site was from 0% to 6.4% (P =.06) for outpatients and from 49.2% to 77.3% for inpatients (P <.001), while PO use ranged from 9.4% to 57.8% for outpatients (P <.001) and from 47.9% to 85.1% for inpatients (P <.001). Differences among sites remained after controlling for patient demographic characteristics, comorbidity, and illness severity. In patients with 1 or more measurements of oxygenation at presentation, hypoxemia was independently associated with 6 risk factors: age >30 years (odds ratio (OR], 3.2; 95% confidence Interval [CII, 1.7 to 5.9), chronic obstructive pulmonary disease (OR, 1.9; 95% CI, 1.4 to 2.6), congestive heart failure (OR, 1.5; 95% CI. 1.0 to 2.1), respiratory rate >24 per minute (OR, 2.3; 95% CI, 1.8 to 3.0), altered mental status (OR, 1.6; 95% Cl, 1.1 to 2.3). and chest radiographic infiltrate involving >1 lobe (OR, 2.2; 95% Cl, 1.7 to 2.9). The prevalence of hypoxemia among those tested ranged from 13% for Inpatients with no risk factors to 54.6% for inpatients with greater than or equal to 3 risk factors. Of the 210 outpatients who had greater than or equal to2 of these risk factors, only 64 (30.5%) had either an ABG or PO performed. in the 48 outpatients tested without supplemental O-2 with greater than or equal to2 risk factors 8.3% were hypoxemic.
   CONCLUSIONS: In the initial management of CAP, use of ABG and PO varied widely across sites. Increasing the assessment of arterial oxygenation among patients with CAP Is likely to increase the detection of arterial hypoxemia, particularly among outpatients.
C1 VA Pittsburgh Med Ctr, VA Pittsburgh Ctr Hlth Serv Res, Pittsburgh, PA 15240 USA.
   Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA.
   Univ Pittsburgh, Ctr Res Hlth Care, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA USA.
   Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Univ Alberta, Dept Med, Edmonton, AB, Canada.
RP Fine, MJ (reprint author), VA Pittsburgh Med Ctr, VA Pittsburgh Ctr Hlth Serv Res, 130-U,Univ Dr C,11th Floor,11E127, Pittsburgh, PA 15240 USA.
FU AHRQ HHS [R01 HSO6468]
NR 16
TC 29
Z9 31
U1 0
U2 1
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 SEP
PY 2001
VL 16
IS 9
BP 590
EP 598
DI 10.1046/j.1525-1497.2001.016009590.x
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 475TV
UT WOS:000171184700003
PM 11556939
ER

PT J
AU Halm, EA
   Switzer, GE
   Mittman, BS
   Walsh, MB
   Chang, CCH
   Fine, MJ
AF Halm, EA
   Switzer, GE
   Mittman, BS
   Walsh, MB
   Chang, CCH
   Fine, MJ
TI What factors influence physicians' decisions to switch from intravenous
   to oral antibiotics for community-acquired pneumonia?
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE antibiotic therapy; streamlining; pneumonia; physician attitudes
ID IN-HOSPITAL OBSERVATION; ANTIMICROBIAL THERAPY; PRACTICE GUIDELINES;
   OUTCOMES; LENGTH; STAY; MANAGEMENT; DISCHARGE; ATTITUDES; PATIENT
AB OBJECTIVE: One of the major factors influencing length of stay for patients with community-acquired pneumonia is the timing of conversion from intravenous to oral antibiotics. We measured physician attitudes and beliefs about the antibiotic switch decision and assessed physician characteristics associated with practice beliefs.
   DESIGN: Written survey assessing attitudes about the antibiotic conversion decision.
   SETTING: Seven teaching and non-teaching hospitals in Pittsburgh, Pa.
   PARTICIPANTS: Three hundred forty-five generalist and specialist attending physicians who manage pneumonia in 7 hospitals.
   MEASUREMENTS AND RESULTS: Factors rated as "very important" to the antibiotic conversion decision were: absence of suppurative infection (93%), ability to maintain oral intake (79%), respiratory rate at baseline (64%), no positive blood cultures (63%), normal temperature (62%). oxygenation at baseline (55%). and mental status at baseline (50%). The median thresholds at which physicians believed a typical patient could be converted to oral therapy were: temperature less than or equal to 100 degreesF (37.8 degreesC), respiratory rate less than or equal to 20 breaths/ minute, heart rate less than or equal to 100 beats/minute, systolic blood pressure greater than or equal to 100 mm Hg, and room air oxygen saturation greater than or equal to 90%. Fifty-eight percent of physicians felt that "patients should be afebrile for 24 hours before conversion to oral antibiotics," and 19% said, "patients should receive a standard duration of Intravenous antibiotics." In univariate analyses, pulmonary and infectious diseases physicians were the most predisposed towards early conversion to oral antibiotics, and other medical specialists were the least predisposed, with generalists being intermediate (P <.019). In multivariate analyses, practice beliefs were associated with age, Inpatient care activities, attitudes about guidelines. and agreeableness on a personality inventory scale.
   CONCLUSIONS: Physicians believed that patients could be switched to oral antibiotics once vital signs and mental status had stabilized and oral intake was possible. However, there was considerable variation in several antibiotic practice beliefs. Guidelines and pathways to streamline antibiotic therapy should include educational strategies to address some of these differences In attitudes.
C1 CUNY Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA.
   CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA.
   Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA.
   Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA.
   VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA.
   RAND Corp, Santa Monica, CA USA.
   VA Pittsburgh Healthcare Syst, VA Pittsburgh Ctr Hlth Serv Res, Pittsburgh, PA USA.
RP Halm, EA (reprint author), CUNY Mt Sinai Sch Med, Dept Hlth Policy, Box 1077,1 Gustave L Levy Pl, New York, NY 10029 USA.
FU AHRQ HHS [R01 HS08282-02]
NR 27
TC 29
Z9 30
U1 0
U2 0
PU BLACKWELL SCIENCE INC
PI MALDEN
PA 350 MAIN ST, MALDEN, MA 02148 USA
SN 0884-8734
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD SEP
PY 2001
VL 16
IS 9
BP 599
EP 605
DI 10.1046/j.1525-1497.2001.016009599.x
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA 475TV
UT WOS:000171184700004
PM 11556940
ER

PT J
AU Rosowsky, A
   Fu, HN
   Queener, SF
AF Rosowsky, A
   Fu, HN
   Queener, SF
TI Synthesis of new 2,4-diamino-7H-pyrrolo[2,3-d]pyrimidines via the Taylor
   ring transformation/ring annulation strategy
SO JOURNAL OF HETEROCYCLIC CHEMISTRY
LA English
DT Article
ID DIHYDROFOLATE-REDUCTASE; PNEUMOCYSTIS-CARINII; TOXOPLASMA-GONDII;
   INHIBITORS; PYRROLO<2,3-D>PYRIMIDINES; POTENT
AB Selected examples 2,4-diamino-7H-pyrrolo[2,3-d]pyrimidines with a phenyl or benzyl group at the 5-position were synthesized as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii and Toxoplasma gondii, two potentially life-threatening opportunistic pathogens associated with AIDS and other disorders of the immune system. Aldol condensation of paraformaldehyde with substituted benzaldehydes or with phenylacetaldehyde afforded alpha -hydroxyketones with a phenyl or benzyl group at the 4-position. Further reaction of the hydroxyketones with malononitrile afforded 2-aminofuran-3-carbonitriles, which upon heating with guanidine underwent ring transformation/ring annulation to produce 2,4-diamino-7H-pyrrolo[2,3-d]pyrimidines rather than 2,4-diaminofuro[2,3-d]pyrimidines. One of the target compounds obtained in this manner, 2,4-diamino-5-(3,4,5-trimethoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine (1d), may be viewed as a conformationally restricted analogue of trimethoprim, an antimicrobial agent widely used in combination with a sulfa drug to treat P. carinii and T. gondii opportunistic infections in patients with AIDS. Compound Id inhibited P. carinii and T gondii DHFR with IC50 values of 8.3 and 14 muM, respectively. This potency was somewhat greater than that of trimethoprim. However, because this compound was also more potent than trimethoprim against mammalian (rat liver) DHFR rat liver it lacked species selectivity. The other 2,4-diamino-7H-pyrrolo[2,3-d]pyrimidines synthesized were neither potent nor selective.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
   Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA.
RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
NR 13
TC 9
Z9 10
U1 1
U2 2
PU HETERO CORPORATION
PI ODESSA
PA PO BOX 993, ODESSA, FL 33556-0993 USA
SN 0022-152X
J9 J HETEROCYCLIC CHEM
JI J. Heterocycl. Chem.
PD SEP-OCT
PY 2001
VL 38
IS 5
BP 1197
EP 1202
PG 6
WC Chemistry, Organic
SC Chemistry
GA 484TB
UT WOS:000171704700026
ER

PT J
AU Verschoor, A
   Brockman, MA
   Knipe, DM
   Carroll, MC
AF Verschoor, A
   Brockman, MA
   Knipe, DM
   Carroll, MC
TI Cutting edge: Myeloid complement C3 enhances the humoral response to
   peripheral viral infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HERPES-SIMPLEX VIRUS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; FOLLICULAR
   DENDRITIC CELLS; TUBULAR EPITHELIAL-CELLS; TYPE-1 GLYCOPROTEIN GC;
   IMMUNE-RESPONSE; IFN-GAMMA; NERVOUS-SYSTEM; MICE DEFICIENT; COMPONENT C3
AB HSV-1 is the causative agent of cutaneous lesions, commonly referred to as cold sores. Primary exposure to the virus ordinarily occurs through the periphery, in particular through abraded skin or mucosal membranes. Under certain circumstances (e.g., in neonatals or AIDS patients), the infection becomes disseminated, often with severe consequences. Spread of HSV-1 is limited by virus-specific Ab. The development of an efficient Immoral response to the virus is dependent on innate immunity component complement C3. The liver is the major source of C3, but there are also extrahepatic origins of C3 such as lymphoid macrophages. In the present study, the significance of C3 synthesis by bone marrow-derived cells was assessed by the transfer of wild-type bone marrow into irradiated C3-deficient mice. Using these chimeric mice, extrahepatic C3 was determined sufficient to initiate specific Ab and memory responses to a peripheral HSV-1 infection.
C1 Ctr Blood Res, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA.
   Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA.
   Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Cambridge, MA 02138 USA.
RP Carroll, MC (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA.
OI Brockman, Mark/0000-0001-6432-1426
FU NIAID NIH HHS [AI-42257]
NR 56
TC 46
Z9 48
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 SEP 1
PY 2001
VL 167
IS 5
BP 2446
EP 2451
PG 6
WC Immunology
SC Immunology
GA 496JE
UT WOS:000172391800003
PM 11509581
ER

PT J
AU Altfeld, M
   Addo, MM
   Eldridge, RL
   Yu, XG
   Thomas, S
   Khatri, A
   Strick, D
   Phillips, MN
   Cohen, GB
   Islam, SA
   Kalams, SA
   Brander, C
   Goulder, PJR
   Rosenberg, ES
   Walker, BD
AF Altfeld, M
   Addo, MM
   Eldridge, RL
   Yu, XG
   Thomas, S
   Khatri, A
   Strick, D
   Phillips, MN
   Cohen, GB
   Islam, SA
   Kalams, SA
   Brander, C
   Goulder, PJR
   Rosenberg, ES
   Walker, BD
CA HIV Study Collaboration
TI Vpr is preferentially targeted by CTL during HIV-1 infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE RESPONSES; CELL-CYCLE
   ARREST; NUCLEAR-LOCALIZATION; MUTATIONAL ANALYSIS; VIF PROTEIN; VIRION
   INCORPORATION; FINE SPECIFICITY; PROVIRAL DNA; G(2) ARREST
AB The HIV-1 accessory proteins Vpr, Vpu, and Vif are essential for viral replication, and their cytoplasmic production suggests that they should be processed for recognition by CTLs. However, the extent to which these proteins are targeted in natural infection, as well as precise CTL epitopes within them, remains to be defined. In this study, CTL responses against HIV-1 Vpr, Vpu, and Vif were analyzed in 60 HIV-1-infected individuals and 10 HIV-1-negative controls using overlapping peptides spanning the entire proteins. Peptide-specific IFN-gamma production was measured by ELISPOT assay and flow-based intracellular cytokine quantification. HLA class I restriction and cytotoxic activity were confirmed after isolation of peptide-specific CD8(+) T cell lines. CD8(+) T cell responses against Vpr, Vpu, and Vif were found in 45%, 2%, and 33% of HIV-1-infected individuals, respectively. Multiple CTL epitopes were identified in functionally important regions of HIV-1 Vpr and Vif. Moreover, in infected individuals in whom the breadth of HIV-1-specific responses was assessed comprehensively, Vpr and p17 were the most preferentially targeted proteins per unit length by CD8(+) T cells. These data indicate that despite the small size of these proteins Vif and Vpr are frequently targeted by CTL in natural HIV-1 infection and contribute importantly to the total HIV-1-specific CD8(+) T cell responses. These findings will be important in evaluating the specificity and breadth of immune responses during acute and chronic infection, and in the design and testing of candidate HIV vaccines.
C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA.
   Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA.
   Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA.
   Harvard Univ, Sch Med, Boston, MA 02129 USA.
   China Med Univ, Affiliated Hosp 1, Ctr AIDS Res, Shenyang, Peoples R China.
   John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England.
   Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   Fenway Community Hlth Ctr, Boston, MA 02116 USA.
RP Walker, BD (reprint author), Massachusetts Gen Hosp E, CNY 5212,149 13th St, Charlestown, MA 02129 USA.
OI Thomas, Seddon/0000-0003-0075-0744
FU NIAID NIH HHS [R01 AI30914, R01 AI40873, R01 AI44656, R37 AI128568, U01
   AI41531, U01 AI41535]
NR 65
TC 90
Z9 92
U1 1
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
J9 J IMMUNOL
JI J. Immunol.
PD SEP 1
PY 2001
VL 167
IS 5
BP 2743
EP 2752
PG 10
WC Immunology
SC Immunology
GA 496JE
UT WOS:000172391800040
PM 11509618
ER

PT J
AU Ryan, ET
   Bridges, EA
   Crean, TI
   Gausia, K
   Hamadani, JD
   Aziz, A
   Hawkes, S
   Begum, M
   Bogaerts, J
   Faruque, SM
   Salam, MA
   Fuchs, GJ
   Calderwoods, SB
AF Ryan, ET
   Bridges, EA
   Crean, TI
   Gausia, K
   Hamadani, JD
   Aziz, A
   Hawkes, S
   Begum, M
   Bogaerts, J
   Faruque, SM
   Salam, MA
   Fuchs, GJ
   Calderwoods, SB
TI Local production of anti-Vibrio cholerae mucosal antibody in
   reproductive tract tissues after cholera
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article; Proceedings Paper
CT 49th Annual Meeting of the
   American-Society-of-Tropical-Medicine-and-Hygiene
CY OCT 29-NOV 02, 2000
CL HOUSTON, TEXAS
SP Amer Soc Trop Med & Hyg
ID FEMALE GENITAL-TRACT; TOXIN-B-SUBUNIT; ESCHERICHIA-COLI; IMMUNIZATION;
   SECRETIONS; INDUCTION; RESPONSES; IMMUNITY; VACCINE; DISEASE
AB To investigate whether intestinal presentation of an antigen by Vibrio cholerae, a noninvasive organism, could induce an anatomically distant mucosal immune response in reproductive tract tissues, the endocervical immune responses of women in Bangladesh were evaluated after cholera. Endocervical secretions were analyzed for secretory IgA (sIgA) antibody against the B subunit of cholera toxin (CtxB) in 9 women with cholera and 8 women with diarrhea caused by neither V. cholerae nor heat labile enterotoxin-producing Escherichia coli. Women infected with V. cholerae developed significant sIgA anti-CtxB responses in endocervical samples (P less than or equal to .02). Antibody subtype analysis of endocervical IgA was consistent with local mucosal production (P less than or equal to .001). Women with cholera did not develop sIgA anti-CtxB responses in serum. The ability to generate specific mucosal immune responses in reproductive tract tissues after intestinal presentation of antigen could facilitate development of vaccines effective against reproductive tract pathogens.
C1 Massachusetts Gen Hosp, Div Infect Dis, Trop & Geog Med Ctr, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
   Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA.
   Louisiana State Univ, Sch Med, Dept Pediat, New Orleans, LA USA.
   ICDDR B, Ctr Hlth & Populat Res, Dhaka, Bangladesh.
RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Trop & Geog Med Ctr, Jackson 504,55 Fruit St, Boston, MA 02114 USA.
OI Gausia, Kaniz/0000-0003-2499-1403
FU NIAID NIH HHS [AI-40725, R01 AI040725, AI-01332]; NICHD NIH HHS [U01
   HD039165, HD-39165]
NR 15
TC 1
Z9 6
U1 0
U2 0
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 SEP 1
PY 2001
VL 184
IS 5
BP 643
EP 647
DI 10.1086/322807
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 462PR
UT WOS:000170429400018
PM 11494170
ER

PT J
AU Astuti, D
   Latif, F
   Dallol, A
   Dahia, PLM
   Douglas, F
   Skoldberg, F
   Husebye, ES
   Eng, C
   Maher, ER
AF Astuti, D
   Latif, F
   Dallol, A
   Dahia, PLM
   Douglas, F
   Skoldberg, F
   Husebye, ES
   Eng, C
   Maher, ER
TI Mutations in the mitochondrial complex II subunit SDHB cause
   susceptibility to familial phaeochromocytoma and paraganglioma.
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Meeting Abstract
C1 Univ Birmingham, Sect Med & Mol Genet, Dept Paediat & Child Hlth, Birmingham B15 2TT, W Midlands, England.
   Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
   Royal Victoria Infirm, No Reg Genet Serv, Newcastle Upon Tyne NE2, Tyne & Wear, England.
   Univ Uppsala, Dept Med Sci, S-75105 Uppsala, Sweden.
   Ohio State Univ, Clin Canc Genet Program, Columbus, OH 43210 USA.
   Ohio State Univ, Human Canc Genet Program, Columbus, OH 43210 USA.
   Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA.
   Ohio State Univ, Dept Internal Med, Div Human Genet, Columbus, OH 43210 USA.
   CRC, Human Canc Genet Res Grp, Cambridge, England.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU BRITISH MED JOURNAL PUBL GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
J9 J MED GENET
JI J. Med. Genet.
PD SEP
PY 2001
VL 38
SU 1
MA SP42
BP S22
EP S22
PG 1
WC Genetics & Heredity
SC Genetics & Heredity
GA 473NV
UT WOS:000171051200041
ER

PT J
AU Mann, DL
AF Mann, DL
TI Interleukin-6 and viral myocarditis: The Yin-Yang of cardiac innate
   immune responses
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Editorial Material
DE myocarditis; innate immunity; tumor necrosis factor; interleukin-6
ID TUMOR-NECROSIS-FACTOR; MICE; IL-6; RECEPTOR; TNF
C1 Houston Vet Adm Med Ctr, Houston, TX 77030 USA.
   Baylor Coll Med, Dept Med, Cardiol Sect, Winters Ctr Heart Failure Res, Houston, TX 77030 USA.
RP Mann, DL (reprint author), Houston Vet Adm Med Ctr, 151C,2002 Holcombe Blvd, Houston, TX 77030 USA.
EM dmann@bcm.tmc.edu
OI Mann, Douglas /0000-0002-2516-0145
FU NHLBI NIH HHS [R01 HL58081-01, P50 HL-06H, HL-42250-10/10, R01
   HL61543-01]
NR 15
TC 7
Z9 7
U1 0
U2 1
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 SEP
PY 2001
VL 33
IS 9
BP 1551
EP 1553
DI 10.1006/jmcc.2001.1432
PG 3
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA 471FX
UT WOS:000170919100001
PM 11549335
ER

PT J
AU Stanislaus, R
   Singh, AK
   Singh, I
AF Stanislaus, R
   Singh, AK
   Singh, I
TI Amelioration of experimental allergic encephalomyelitis in Lewis rats by
   Lovastatin: a novel role for statins.
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
C1 Ralph H Johnson VA Med Ctr, Dept Pathol & Lab Med, Charleston, SC USA.
   Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 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 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD SEP
PY 2001
VL 78
SU 1
BP 47
EP 47
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 469AF
UT WOS:000170789800165
ER

PT J
AU Reddy, RD
   Keshavan, MS
   Yao, JK
AF Reddy, RD
   Keshavan, MS
   Yao, JK
TI Altereded plasma antioxidant status in first-episode schizophrenic
   patients
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
C1 Univ Pittsburgh, Med Ctr, WPIC, Pittsburgh, PA 15238 USA.
   VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 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 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD SEP
PY 2001
VL 78
SU 1
BP 79
EP 79
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 469AF
UT WOS:000170789800278
ER

PT J
AU Yao, JK
   Leonard, S
   Reddy, RD
AF Yao, JK
   Leonard, S
   Reddy, RD
TI Increased nitric oxide radicals and mercaptans in postmortem brains from
   schizophrenic patients
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA.
   Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15206 USA.
   Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 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 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD SEP
PY 2001
VL 78
SU 1
BP 89
EP 89
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 469AF
UT WOS:000170789800317
ER

PT J
AU Bush, AI
AF Bush, AI
TI Abnormal catalytic redox activity of A beta in Alzheimer's disease, and
   SOD in ALS
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Oxidat Biol, Charlestown, MA USA.
   Univ Melbourne, Mental Hlth Res Inst, Melbourne, Vic, Australia.
RI Bush, Ashley/A-1186-2007
OI Bush, Ashley/0000-0001-8259-9069
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 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD SEP
PY 2001
VL 78
SU 1
BP 103
EP 103
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 469AF
UT WOS:000170789800363
ER

PT J
AU Dwyer, A
   Sekiguchi, J
   Frank, K
   Okada, A
   McConnell, SK
   Alt, FW
   Rathbun, GA
AF Dwyer, A
   Sekiguchi, J
   Frank, K
   Okada, A
   McConnell, SK
   Alt, FW
   Rathbun, GA
TI Linkage of DNA end joining components and embryonic neurogenesis
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU 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 SEP
PY 2001
VL 78
SU 1
BP 118
EP 118
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 469AF
UT WOS:000170789800410
ER

PT J
AU Yao, JK
   van Kammen, DP
   Peters, JL
   Gurklis, JA
AF Yao, JK
   van Kammen, DP
   Peters, JL
   Gurklis, JA
TI CSF serine levels in schizophrenia
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA.
   Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15206 USA.
   RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 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 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD SEP
PY 2001
VL 78
SU 1
BP 158
EP 158
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 469AF
UT WOS:000170789800565
ER

PT J
AU Hagerty, T
   Fernandez, E
   Lynch, K
   Wang, SS
   Morgan, WW
   Strong, R
AF Hagerty, T
   Fernandez, E
   Lynch, K
   Wang, SS
   Morgan, WW
   Strong, R
TI Interaction of a glucocorticoid-responsive element with regulatory
   sequences in the promoter region of the mouse tyrosine hydroxylase gene
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE cyclic AMP-responsive element; cyclic AMP-dependent protein kinase; gene
   promoter; gene transcription; glucocorticoid response element; tyrosine
   hydroxylase
ID DOPAMINE BETA-HYDROXYLASE; CYCLIC-AMP; PROTEIN-KINASE; MEMBRANE
   DEPOLARIZATION; TRANSCRIPTION FACTORS; MESSENGER-RNA; PC12 CELLS;
   EXPRESSION; INDUCTION; RAT
AB The purpose of the work reported here was to determine whether the tyrosine hydroxylase glucocorticoid-responsive element (TH-GRE) interacts with the cyclic AMP pathway and the CRE in regulating mouse TH promoter activity, and whether an additional, previously identified downstream GRE-like element also participates in the function of the TH-GRE and CRE. To determine the role of the cAMP pathway on TH-GRE function, we compared the effects of forskolin and dexamethasone on TH mRNA, TH gene transcription and TH promoter activity in a mutant PC12 cell line (A126-1B2) deficient in cAMP-dependent protein kinase A (PKA) with their effects in the wild-type parental strain. Forskolin treatment increased TH mRNA content, transcriptional activity and the activity of a chimeric gene with 3.6 kb of the TH promoter in wild-type cells, but not in PKA-deficient cells. In contrast, dexamethasone treatment stimulated equivalent increases in TH mRNA, TH gene transcription and TH promoter activity in each cell type. Mutation of the CRE in chimeric constructs containing 3.6 kb of the 5 ' flanking sequence of the mouse TH gene or coexpression of a dominant-negative mutant of CREB prevented the stimulation of TH promoter activity by forskolin. However, neither the mutation of the CRE nor inhibition of CREB influenced basal or dexamethasone-stimulated promoter activity. Site-directed mutagenesis of the TH-GRE eliminated the response of the promoter to dexamethasone. However, the mutagenesis of a more proximal 15-bp region with a GRE-like sequence had no demonstrable effect on the ability of dexamethasone to stimulate TH promoter activity. Neither mutagenesis of the TH-GRE or the downstream GRE-like sequence had an effect on the ability of forskolin to activate this chimeric gene. Taken together, these results provide evidence that a single GRE is sufficient for maximal induction of transcriptional activity by glucocorticoids and that the CRE is not required for either partial or full activity of this upstream GRE sequence.
C1 Audie L Murphy Vet Hosp, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78284 USA.
   Audie L Murphy Vet Hosp, Res Serv, San Antonio, TX 78284 USA.
   Univ Texas, Ctr Hlth Sci, Dept Pharmacol, San Antonio, TX USA.
   Univ Texas, Ctr Hlth Sci, Dept Cellular & Struct Biol, San Antonio, TX USA.
RP Strong, R (reprint author), Audie L Murphy Vet Hosp, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA.
FU NIDDK NIH HHS [DK 52543]
NR 37
TC 30
Z9 30
U1 0
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 SEP
PY 2001
VL 78
IS 6
BP 1379
EP 1388
DI 10.1046/j.1471-4159.2001.00521.x
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 474LF
UT WOS:000171107900019
PM 11579146
ER

PT J
AU Taber, KH
   Rashid, A
   Hurley, RA
AF Taber, KH
   Rashid, A
   Hurley, RA
TI Functional anatomy of central pain
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Article
ID CENTRAL POSTSTROKE PAIN; MOTOR CORTEX STIMULATION; NEUROPATHIC PAIN;
   MECHANISM; THALAMUS; NUCLEUS; STROKE; BRAIN; MRI
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.
RP Taber, KH (reprint author), Baylor Coll Med, Dept Radiol, 1 Baylor Plaza, Houston, TX 77030 USA.
NR 34
TC 2
Z9 2
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 FAL
PY 2001
VL 13
IS 4
BP 437
EP 440
DI 10.1176/appi.neuropsych.13.4.437
PG 4
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 501VX
UT WOS:000172707700001
PM 11748313
ER

PT J
AU Nahas, Z
   Teneback, HC
   Kozel, A
   Speer, AM
   DeBrux, C
   Molloy, M
   Stallings, L
   Spicer, KM
   Arana, G
   Bohning, DE
   Risch, SC
   George, MS
AF Nahas, Z
   Teneback, HC
   Kozel, A
   Speer, AM
   DeBrux, C
   Molloy, M
   Stallings, L
   Spicer, KM
   Arana, G
   Bohning, DE
   Risch, SC
   George, MS
TI Brain effects of TMS delivered over prefrontal cortex in depressed
   adults: Role of stimulation frequency and coil-cortex distance
SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Article
ID TRANSCRANIAL MAGNETIC STIMULATION; LONG-TERM POTENTIATION; MOTOR CORTEX;
   MAJOR DEPRESSION; ANTIDEPRESSANT RESPONSE; RTMS; MOOD; PET;
   EXCITABILITY; CONNECTIVITY
AB Relative regional brain blood flow was measured in 23 clinically depressed adults by using ECD SPECT at baseline and again during actual prefrontal transcranial magnetic stimulation (TMS) following 5 daily sessions of TMS. TMS over prefrontal cortex caused increased activity in cortex directly under the stimulation (inversely correlated with distance from scalp to cortex) and decreased activity in remote regions (anterior cingulate and anterior temporal poles). High-frequency rTMS (20 Hz) caused more relative flow immediately below the TMS coil than did low-frequency rTMS (5 Hz). Confirming the hypotheses tested, repeated daily TMS over the prefrontal cortex in medication-free depressed adults appears to change both local and remote blood flow in a manner that may also depend on the frequency of stimulation and coil to outer cortex distance.
C1 Med Univ S Carolina, Dept Radiol, Funct Neuroimaging Res Div, Brain Simulat Lab, Charleston, SC 29425 USA.
   Med Univ S Carolina, Dept Psychiat, Funct Neuroimaging Res Div, Brain Simulat Lab, Charleston, SC 29425 USA.
   Med Univ S Carolina, Dept Neurol, Funct Neuroimaging Res Div, Brain Simulat Lab, Charleston, SC 29425 USA.
   Ralph H Johnson Vet Hosp, Charleston, SC USA.
RP Nahas, Z (reprint author), Med Univ S Carolina, Dept Radiol, Funct Neuroimaging Res Div, Brain Simulat Lab, 171 Ashley Ave, Charleston, SC 29425 USA.
NR 60
TC 77
Z9 79
U1 1
U2 2
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 FAL
PY 2001
VL 13
IS 4
BP 459
EP 470
DI 10.1176/appi.neuropsych.13.4.459
PG 12
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 501VX
UT WOS:000172707700003
PM 11748315
ER

PT J
AU Li, MT
   Linseman, DA
   Allen, MP
   Meintzer, MK
   Wang, XM
   Laessig, T
   Wierman, ME
   Heidenreich, KA
AF Li, MT
   Linseman, DA
   Allen, MP
   Meintzer, MK
   Wang, XM
   Laessig, T
   Wierman, ME
   Heidenreich, KA
TI Myocyte enhancer factor 2A and 2D undergo phosphorylation and
   caspase-mediated degradation during apoptosis of rat cerebellar granule
   neurons
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE MEF2; neurons; apoptosis; transcription; caspase; cerebellum
ID TRANSCRIPTION FACTOR MEF2; ACTIVATED PROTEIN-KINASE;
   CENTRAL-NERVOUS-SYSTEM; EXPRESSION; MUSCLE; SKELETAL; CELLS; GENE;
   DIFFERENTIATION; SURVIVAL
AB Myocyte enhancer factor 2 (MEF2) proteins are important regulators of gene expression during the development of skeletal, cardiac, and smooth muscle. MEF2 proteins are also present in brain and recently have been implicated in neuronal survival and differentiation. In this study we examined the cellular mechanisms regulating the activity of MEF2s during apoptosis of cultured cerebellar granule neurons, an established in vitro model for studying depolarization-dependent neuronal survival. All four MEF2 isoforms (A, B, C, and D) were detected by immunoblot analysis in cerebellar granule neurons. Endogenous MEF2A and MEF2D, but not MEF2B or MEF2C, were phosphorylated with the induction of apoptosis. The putative sites that were phosphorylated during apoptosis are functionally distinct from those previously reported to enhance MEF2 transcription. The increased phosphorylation of MEF2A and MEF2D was followed by decreased DNA binding, reduced transcriptional activity, and caspase-dependent cleavage to fragments containing N-terminal DNA binding domains and C-terminal transactivation domains. Expression of the highly homologous N terminus of MEF2A (1-131 amino acids) antagonized the transcriptional activity and prosurvival effects of a constitutively active mutant of MEF2D (MEF2D-VP16). We conclude that MEF2A and MEF2D are prosurvival factors with high transcriptional activity in postmitotic cerebellar granule neurons. When these neurons are induced to undergo apoptosis by lowering extracellular potassium, MEF2A and MEF2D are phosphorylated, followed by decreased DNA binding and cleavage by a caspase-sensitive pathway to N-terminal fragments lacking the transactivation domains. The degradation of MEF2D and MEF2A and the generation of MEF2 fragments that have the potential to act as dominant-inactive transcription factors lead to apoptotic cell death.
C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA.
   Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA.
   Denver Vet Affairs Med Ctr, Denver, CO 80262 USA.
RP Heidenreich, KA (reprint author), Denver Vet Affairs Med Ctr 111H, 1055 Clermont St, Denver, CO 80220 USA.
FU NINDS NIH HHS [NS38619-01A1]
NR 33
TC 89
Z9 90
U1 1
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 SEP 1
PY 2001
VL 21
IS 17
BP 6544
EP 6552
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 467FC
UT WOS:000170690900012
PM 11517243
ER

PT J
AU Ko, J
   Humbert, S
   Bronson, RT
   Takahashi, S
   Kulkarni, AB
   Li, E
   Tsai, LH
AF Ko, J
   Humbert, S
   Bronson, RT
   Takahashi, S
   Kulkarni, AB
   Li, E
   Tsai, LH
TI p35 and p39 are essential for cyclin-dependent kinase 5 function during
   neurodevelopment
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE p35; p39; Cdk5; development; lamination; neuronal migration; Nudel;
   neurofilaments
ID CDK5 ACTIVATOR P35; SONIC HEDGEHOG; NERVOUS-SYSTEM; CORTICAL
   DEVELOPMENT; REGULATORY SUBUNIT; LISSENCEPHALY GENE; INFERIOR OLIVE;
   P35(-/-) MICE; KDA SUBUNIT; NEUROFILAMENT
AB Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in brain development and neuronal migration. Cdk5 is abundant in postmitotic, terminally differentiated neurons. The ability of Cdk5 to phosphorylate substrates is dependent on activation by its neuronal-specific activators p35 and p39. There exist striking differences in the phenotypic severity of Cdk5-deficient mice and p35-deficient mice. Cdk5-null mutants show a more severe disruption of lamination in the cerebral cortex, hippocampus, and cerebellum. In addition, Cdk5-null mice display perinatal lethality, whereas p35-null mice are viable. These discrepancies have been attributed to the function of other Cdk5 activators, such as p39. To understand the roles of p39 and p35, we created p39-null mice and p35/p39 compound-mutant mice. Interestingly, p39-null mice show no obvious detectable abnormalities, whereas p35(-/-)p39(-/-) double-null mutants are perinatal lethal. We show here that the p35(-/-)p39(-/-) mutants exhibit phenotypes identical to those of the Cdk5-null mutant mice. Other compound-mutant mice with intermediate phenotypes allow us to determine the distinct and redundant functions between p35 and p39. Our data strongly suggest that p35 and p39 are essential for Cdk5 activity during the development of the nervous system. Thus, p35 and p39 are likely to be the principal, if not the only, activators of Cdk5.
C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02215 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA.
   Ctr Univ Orsay, Inst Curie, CNRS, Unite Mixte Rech 146, F-91405 Orsay, France.
   Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA.
   Natl Inst Dent & Craniofacial Res, Funct Genom Unit, NIH, Bethesda, MD 20892 USA.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA.
RP Tsai, LH (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 200 Longwood Ave, Boston, MA 02215 USA.
RI Humbert, Sandrine/S-2981-2016
FU NIGMS NIH HHS [GM53049]
NR 64
TC 256
Z9 276
U1 2
U2 4
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD SEP 1
PY 2001
VL 21
IS 17
BP 6758
EP 6771
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 467FC
UT WOS:000170690900033
PM 11517264
ER

PT J
AU Labow, BI
   Souba, WW
   Abcouwer, SF
AF Labow, BI
   Souba, WW
   Abcouwer, SF
TI Mechanisms governing the expression of the enzymes of glutamine
   metabolism - Glutaminase and glutamine synthetase
SO JOURNAL OF NUTRITION
LA English
DT Article; Proceedings Paper
CT Symposium on Glutamine
CY OCT, 2000
CL BERMUDA
DE glutamine; glutamine synthetase; 26S proteosome
ID PHOSPHATE-DEPENDENT GLUTAMINASE; RAT HEPATIC GLUTAMINASE; MESSENGER-RNA;
   RENAL GLUTAMINASE; ORNITHINE DECARBOXYLASE; GENE-EXPRESSION;
   MITOCHONDRIAL GLUTAMINASE; PRIMARY CULTURES; SKELETAL-MUSCLE;
   ZETA-CRYSTALLIN
AB Whether on the scale of a single cell, organ or organism, glutamine homeostasis is to a large extent determined by the activities of glutaminase (GA, EC 3.5.1.2) and glutamine synthetase (GS, EC 6.3.1.2), the two enzymes that are the focus of this report. GA and GS each provide examples of regulation of gene expression at many different levels. In the case of GA, two different genes (hepatic- and kidney-type GA) encode isoforms of this enzyme. The expression of hepatic GA mRNA is increased during starvation, diabetes and high protein diet through a mechanism involving increased gene transcription. In contrast, the expression of kidney GA mRNA is increased post-transcriptionally by a mechanism that increases mRNA stability during acidosis. We found recently that several isoforms of rat and human kidney-type GA are formed by tissue-specific alternative RNA splicing. Although the implications of this post-transcriptional processing mechanism for GA activity are not yet clear, it allows for the expression of different GA isoforms in different tissues and may limit the expression of GA activity in muscle tissues by diverting primary RNA transcripts to a spliceform that produces a nonfunctional translation product. The expression of GS enzyme is also regulated by both transcriptional and post-transcriptional mechanisms. For example, the GS gene is transcriptionally activated by glucocorticoid hormones in a tissue-specific fashion. This hormonal response allows GS mRNA levels to increase in selected organs during catabolic states. However, the ultimate level of GS enzyme expression is further governed by a post-transcriptional mechanism regulating GS protein stability. In a unique form of product feedback, GS protein turnover is increased by glutamine. This mechanism appears to provide a means to index the production of glutamine to its intracellular concentration and, therefore, to its systemic demand. Herein, we also provide experimental evidence that GS protein turnover is dependent upon the activity of the 26S proteosome.
C1 Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA.
   Penn State Univ, F Edward Herbert Sch Med, Dept Surg, Hershey, PA USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA.
RP Abcouwer, SF (reprint author), Univ New Mexico, Sch Med, Dept Biochem & Mol Biol, Albuquerque, NM 87131 USA.
FU NCI NIH HHS [R29 CA72772]; NHLBI NIH HHS [R01 HL44986]
NR 75
TC 59
Z9 62
U1 1
U2 5
PU AMER INST NUTRITION
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
J9 J NUTR
JI J. Nutr.
PD SEP
PY 2001
VL 131
IS 9
SU S
BP 2467S
EP 2474S
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 472MT
UT WOS:000170988500004
PM 11533295
ER

PT J
AU Gruber, HE
   Ma, DF
   Hanley, EN
   Ingram, J
   Yamaguchi, DT
AF Gruber, HE
   Ma, DF
   Hanley, EN
   Ingram, J
   Yamaguchi, DT
TI Morphologic and molecular evidence for gap junctions and connexin 43 and
   45 expression in annulus fibrosus cells from the human intervertebral
   disc
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
ID INTERCELLULAR COMMUNICATION; DEGENERATION; LINE
AB Data are presented which provide evidence for gap junction formation and connexin (Cx) 43 and 45 gene expression in human intervertebral disc cells in vivo and in vitro. These findings in cells from the annulus are important in conjunction with the well-recognized loss of disc cells during aging and disc degeneration. As a result of this loss of cells, cell-cell communication, which we propose is an important, but as yet poorly understood, mechanism which links and coordinates cellular function throughout the entire population of disc cells, is also disrupted. These studies provide additional information on the fundamental cell biology of the disc cell and provide an additional framework for understanding aging, degeneration and potential repair of the human disc. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
C1 Carolinas Med Ctr, Charlotte, NC 28232 USA.
   Vet Adm Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA.
   Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
RP Gruber, HE (reprint author), Carolinas Med Ctr, POB 32861, Charlotte, NC 28232 USA.
NR 18
TC 15
Z9 18
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0736-0266
J9 J ORTHOPAED RES
JI J. Orthop. Res.
PD SEP
PY 2001
VL 19
IS 5
BP 985
EP 989
DI 10.1016/S0736-0266(00)00072-3
PG 5
WC Orthopedics
SC Orthopedics
GA 468RC
UT WOS:000170771100034
PM 11562151
ER

PT J
AU Winter, HS
AF Winter, HS
TI Transcending therapeutic conventions: Biologic treatment of Crohn's
   disease - Preface
SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
LA English
DT Editorial Material
C1 MassGen Hosp Children, Boston, MA USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Winter, HS (reprint author), MassGen Hosp Children, Boston, MA 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 0277-2116
J9 J PEDIATR GASTR NUTR
JI J. Pediatr. Gastroenterol. Nutr.
PD SEP
PY 2001
VL 33
SU 1
BP S1
EP S2
DI 10.1097/00005176-200109001-00001
PG 2
WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics
GA 481KU
UT WOS:000171519100001
ER

PT J
AU Purucker, P
   Mertes, H
   Goodson, JM
   Bernimoulin, JP
AF Purucker, P
   Mertes, H
   Goodson, JM
   Bernimoulin, JP
TI Local versus systemic adjunctive antibiotic therapy in 28 patients with
   generalized aggressive periodontitis
SO JOURNAL OF PERIODONTOLOGY
LA English
DT Article
DE antibiotics/therapeutic use; periodontal diseases/therapy;
   periodontitis/therapy; tetracycline/therapeutic use
ID TETRACYCLINE FIBER THERAPY; ACTINOMYCETEMCOMITANS-ASSOCIATED
   PERIODONTITIS; RAPIDLY PROGRESSIVE PERIODONTITIS; REFRACTORY
   PERIODONTITIS; MULTICENTER EVALUATION; ADULT PERIODONTITIS;
   CLINICAL-RESPONSE; METRONIDAZOLE; DELIVERY; AMOXYCILLIN
AB Background: Although the use of systemic antibiotics has been studied in patients with generalized aggressive periodontitis (formerly rapidly progressive periodontitis), the use of adjunctive tetracycline fibers in these patients has not been reported. The purpose of the present study was to compare the clinical response of local versus systemic antibiotic treatment as adjuncts to scaling and root planing in patients with GAgP.
   Methods: After initial therapy and full-mouth scaling and root planing (SRP), 30 patients were randomly assigned to 1 of 2 antibiotic treatment groups. Probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were recorded with an automated probe prior to SRP at baseline (BL) and 15, 30, 41, and 54 weeks later. Three months after SRP, the patients were treated with amoxicillin/clavulanic acid (500 mg tid; SRP + AUG group) or with local tetracycline fiber in pockets with PD greater than or equal to5 mm (SRP + TCF group).
   Results: In both treatment groups, PD decreased significantly from BL to week 54 (6.2 +/- 1.5 mm to 4.7 +/- 1.4 mm for SRP + TCF and 6.5 +/- 1.4 mm to 4.2 +/- 0.6 mm for SRP + AUG). However, there was no statistically significant difference between the 2 groups in pocket reduction. Similarly, in both treatment groups, there were small but significant gains in CAL from BL to week 54 (12.0 +/- 1.8 mm to 11.3 +/- 1.8 mm for SRP + TCF and 12.3 +/- 1.5 mm to 11.2 +/- 1.2 mm for SRP + AUG). The difference in CAL gain between the 2 groups was not statistically significant. At the final examination, both groups showed significant PD reduction and CAL gain (P <0.001) compared to BL. The frequency and percentage of bleeding sites decreased significantly in both groups. At week 54, this decrease was significantly greater in the SRP + AUG group (31.67% for SRP + TCF versus 3.85% for SRP + AUG).
   Conclusions: These results indicate that the local delivery of tetracycline by a fiber or the systemic administration of amoxicillin/clavulanic acid given 3 months after scaling and root planing produced similar clinical outcomes over the 9-month observation period.
C1 Forsyth Inst, Dept Periodontol, Boston, MA USA.
   Humboldt Univ, Univ Hosp Charite, Dept Periodontol & Synopt Dent, Berlin, Germany.
RP Purucker, P (reprint author), Humboldt Univ, Univ Hosp Charite, Dept Periodontol, Augustenburger Pl 1, D-13353 Berlin, Germany.
NR 29
TC 15
Z9 17
U1 1
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 SEP
PY 2001
VL 72
IS 9
BP 1241
EP 1245
DI 10.1902/jop.2000.72.9.1241
PG 5
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 475UP
UT WOS:000171187700015
PM 11577957
ER

PT J
AU Aravagiri, M
   Marder, SR
AF Aravagiri, M
   Marder, SR
TI Simultaneous determination of clozapine and its N-desmethyl and N-oxide
   metabolites in plasma by liquid chromatography/electrospray tandem mass
   spectrometry and its application to plasma level monitoring in
   schizophrenic patients.
SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
LA English
DT Article
DE clozapine; norclozapine; clozapine N-oxide; simultaneous determination;
   LC-MS-MS; electrospray; plasma level monitoring
ID SOLID-PHASE EXTRACTION; ULTRAVIOLET DETECTION; HUMAN SERUM
AB A liquid chromatography tandem mass spectrometry (LC-MS-MS) assay method for the simultaneous determination of clozapine and its N-desmethyl (norclozapine) and N-oxide metabolites in human plasma is described, The compounds were extracted from plasma by a single step liquid-liquid extraction procedure and analyzed using a high performance liquid chromatography electrospray tandem mass spectrometer system. The compounds were eluted isocratically on a C-18 column. ionized using positive ion atmospheric pressure electrospray ionization method by a TurboIonspray source and analyzed using multiple reaction monitoring mode. The ion transitions monitored were m/z 327 --> m/z 270 for clozapine, m/z 313 --> m/z 192 for norclozapine, m/z 343 --> m/z 256 for clozapine-N-oxide and m/z 421 --> m/z 201 for internal standard. The standard curves of clozapine, norclozapine and clozapine-N-oxide were linear over the range of 1 ng/ml to 1000 ng/ml when 0.5 ml of plasma was used for the analysis (r(2) > 0.998). Three pooled plasma samples collected from patients who were treated with clozapine were used as long-term quality control samples to check the validity of spiked standard curve samples made at various times. The intra- and inter-assay variations for the spiked standard curve and quality control samples were less than 14%. These variations for the long-term patient quality control samples were less than 11%. The LC-MS-MS assay for simultaneous determination of clozapine, norclozapine and clozapine-N-oxide reported here is highly specific. sensitive, accurate and rapid. This method is currently being used for the plasma level monitoring of clozapine and its N-desmethyl and N-oxide metabolites in patients treated with clozapine. The plasma levels of clozapine. norclozapine and clozapine-N-oxide varied widely within and among patients. The data revealed that the norclozapine and clozapine N-oxide metabolites were present at about 58% +/- 14% and 17% +/- 6% of clozapine concentrations in plasma. respectively. (C) 2001 Elsevier Science B.V. All rights reserved.
C1 VA Greater Los Angeles Hlth Care Syst, Psychopharmacol Unit, Los Angeles, CA 90073 USA.
RP Aravagiri, M (reprint author), VA Greater Los Angeles Hlth Care Syst, Psychopharmacol Unit, 11301 Wilshire Blvd,Rm 4 B151H Bldg 210, Los Angeles, CA 90073 USA.
FU NIMH NIH HHS [MH41573]
NR 31
TC 42
Z9 44
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0731-7085
J9 J PHARMACEUT BIOMED
JI J. Pharm. Biomed. Anal.
PD SEP
PY 2001
VL 26
IS 2
BP 301
EP 311
DI 10.1016/S0731-7085(01)00410-1
PG 11
WC Chemistry, Analytical; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA 464ZE
UT WOS:000170562600014
PM 11470207
ER

PT J
AU Lovich, MA
   Creel, C
   Hong, K
   Hwang, CW
   Edelman, ER
AF Lovich, MA
   Creel, C
   Hong, K
   Hwang, CW
   Edelman, ER
TI Carrier proteins determine local pharmacokinetics and arterial
   distribution of paclitaxel
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE paclitaxel; solubility; diffusion; carrier protein-mediated transport;
   vascular pharmacokinetics
ID MUSCLE CELL-PROLIFERATION; DRUG-DELIVERY; VASCULAR INJURY; TISSUE
   UPTAKE; RAT; HEPARIN; TRANSPORT; BINDING; TAXOL; ANGIOPLASTY
AB The growing use of local drug delivery to vascular tissues has increased interest in hydrophobic compounds. The binding of these drugs to serum proteins raises their levels in solution, but hinders their distribution through tissues. Inside the arterial interstitium, viscous and steric forces and binding interactions impede drug motion. As such, this might be the ideal scenario for increasing the amount of drug delivered to, and residence time within, arterial tissues. We quantified carrier-mediated transport for paclitaxel, a model hydrophobic agent with potential use in proliferative vascular diseases, by determining, in the presence or absence of carrier proteins, the maximum concentration of drug in aqueous solution, the diffusivity in free solution, and the diffusivity in arterial tissues. Whereas solubility of paclitaxel was raised 8.1-, 21-, and 57-fold by physiologic levels of alpha (1)-acid glycoproteins, bovine serum albumin, and calf serum over that in protein-free solution, diffusivity of paclitaxel in free solution was reduced by 41, 49, and 74%, respectively. When paclitaxel mixed in these solutions was applied to arteries both in vitro and in vivo, drug was more abundant at the tissue interface, but protein carriers tended to retain drug in the lumen. Once within the tissue, these proteins did not affect the rate at which drug traverses the tissue because this hydrophobic drug interacted with the abundant fixed proteins and binding sites. The protein binding properties of hydrophobic compounds allow for beneficial effects on transvascular transport, deposition, and distribution, and may enable prolonged effect and rationally guide local and systemic strategies for their administration. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.
C1 MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
   Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA.
RP Edelman, ER (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Room 16-343, Cambridge, MA 02139 USA.
FU NIGMS NIH HHS [GM/HL 49039, GM/HL 60407]
NR 45
TC 83
Z9 85
U1 1
U2 12
PU JOHN WILEY & SONS INC
PI NEW YORK
PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0022-3549
J9 J PHARM SCI
JI J. Pharm. Sci.
PD SEP
PY 2001
VL 90
IS 9
BP 1324
EP 1335
DI 10.1002/jps.1085
PG 12
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
   Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA 472LT
UT WOS:000170986200012
PM 11745785
ER

PT J
AU Cogswell, LP
   Raines, DE
   Parekh, S
   Jonas, O
   Maggio, JE
   Strichartz, GR
AF Cogswell, LP
   Raines, DE
   Parekh, S
   Jonas, O
   Maggio, JE
   Strichartz, GR
TI Development of a novel probe for measuring drug binding to the F1*S
   variant of human alpha 1-acid glycoprotein
SO JOURNAL OF PHARMACEUTICAL SCIENCES
LA English
DT Article
DE alpha 1-acid glycoprotein; drug binding; genetic variants; probes;
   methods
ID HUMAN ALPHA-1-ACID GLYCOPROTEIN; HUMAN ALPHA(1)-ACID GLYCOPROTEIN; HUMAN
   SERUM-ALBUMIN; GENETIC-VARIANTS; AFFINITY ADSORBENT; PROTEIN BINDING;
   FLUORESCENCE; CHROMATOGRAPHY; FRACTIONATION; EXPRESSION
AB A novel probe was developed to measure drug association with the F1*S variant of the human serum protein alpha I-acid glycoprotein (AGP). The molecule 2-hydroxy-3,5-diiodo-N-[2(diethylamino)ethyl]benzamide (DEDIC) binds to AGP, quenching its native fluorescence. This quenching was fitted to a two-site model giving apparent dissociation constants of 0.049 +/- 0.005 and 12 +/- 2 muM (mean +/- SEM). Quenching of each of the separate variants of AGP by DEDIC was itself described by a two-site model, giving for the F1*S variant K-D(F1*s)(1)= 0.041 +/- 0.010 muM and K-D(F1*S)(2) = 29 +/- 7 muM; and for the A variant K-D(A)(1) = 0.31 +/- 0.18 muM and K-D(A)(2) = 8.8 +/- 0.7 muM. The utility of DEDIC in probing drug interactions with isolated variants was demonstrated in competition experiments with the model drugs amitriptyline and bupivacaine. In addition, the selectivity of DEDIC for variant F1*S rendered it capable of probing the binding of drugs (including the variant A-selective drug amitriptyline) to F1*S in a mixture of variants, such as occurs naturally in whole AGP. DEDIC is unique as an F1*S variant-selective probe of drug binding to whole AGP that is also sufficiently soluble to serve as a probe of drug binding to the lower affinity sites on isolated A and F1*S variants. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.
C1 Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Pain Res Ctr, Boston, MA 02115 USA.
   Harvard Univ, Harvard Biophys Program, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Dept Anesthesia & Crit Care Med, Boston, MA 02114 USA.
   Brown Univ, Sch Med, Providence, RI 02912 USA.
   Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA.
   Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
RP Strichartz, GR (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Pain Res Ctr, 75 Francis St, Boston, MA 02115 USA.
NR 27
TC 13
Z9 13
U1 0
U2 0
PU JOHN WILEY & SONS INC
PI NEW YORK
PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA
SN 0022-3549
J9 J PHARM SCI
JI J. Pharm. Sci.
PD SEP
PY 2001
VL 90
IS 9
BP 1407
EP 1423
DI 10.1002/jps.1093
PG 17
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology &
   Pharmacy
SC Pharmacology & Pharmacy; Chemistry
GA 472LT
UT WOS:000170986200020
PM 11745793
ER

PT J
AU Brown, D
   Marshansky, V
AF Brown, D
   Marshansky, V
TI Role of endosomal pH and the vacuolar H+-ATPase in coat protein (ARF6
   and ARNO) recruitment: implications for proximal tubule function and
   Fanconi syndrome
SO JOURNAL OF PHYSIOLOGY-LONDON
LA English
DT Meeting Abstract
CT Meeting of the Physiological-Society
CY JUL 03-04, 2001
CL UNIV SHEFFIELD, SHEFFIELD, ENGLAND
SP Physiolog Soc
HO UNIV SHEFFIELD
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.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA
SN 0022-3751
J9 J PHYSIOL-LONDON
JI J. Physiol.-London
PD SEP
PY 2001
VL 535
SU S
BP 11S
EP 12S
PG 2
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 606ZN
UT WOS:000178766100074
ER

PT J
AU Cruz, GD
   Xue, XN
   LeGeros, RZ
   Halpert, N
   Galvis, DL
   Tavares, M
AF Cruz, GD
   Xue, XN
   LeGeros, RZ
   Halpert, N
   Galvis, DL
   Tavares, M
TI Dental caries experience, tooth loss, and factors associated with unmet
   needs of Haitian immigrants in New York City
SO JOURNAL OF PUBLIC HEALTH DENTISTRY
LA English
DT Article; Proceedings Paper
CT 78th General Session of the
   International-Association-for-Dental-Research
CY APR 05-09, 2000
CL WASHINGTON, D.C.
SP Int Assoc Dent Res
DE dental caries; Haitian immigrants; tooth loss; unmet need
ID ETHIOPIA
AB Objective: The aim of this study was to characterize the dental caries experience, tooth loss, and unmet need of a group of Haitian immigrant residents of New York City. Methods: A purposive sample of 523 adults was obtained through community outreach activities during 1997-98. Clinical examinations were performed by calibrated examiners, according to NIDCR criteria. A comprehensive survey also was administered to all the participants. Results: For the whole group, the mean number of missing teeth was 2.64 (SD=4.12), the mean DMFT=6.05 (SD=5.26), the mean DMFS=18.80 (SD=21.04), and the mean DFS=5.58 (SD=6.17). Seventeen percent of the subjects had all their teeth sound, 59 percent had at least one tooth missing, 60 percent had at least one decayed tooth, and only 38 percent had restorations. Multivariate analyses showed that age, sex, education, dental insurance, frequency of dental visits, and dental floss use were predictors of unmet need. Conclusions: Although results showed a relatively low caries experience among this group of Haitian immigrants, the unmet need was very high. Furthermore, the tooth loss experience was relatively high for all age groups, further denoting a lack of access to preventive and restorative services.
C1 NYU, Coll Dent, Dept Epidemiol & Hlth Promot, New York, NY 10010 USA.
   NYU, Sch Med, Dept Environm Med, New York, NY 10010 USA.
   NYU, Coll Dent, Minor Oral Hlth Res Ctr, New York, NY 10010 USA.
   Forsyth Inst, Boston, MA USA.
RP Cruz, GD (reprint author), NYU, Coll Dent, Dept Epidemiol & Hlth Promot, 345 E 24th St,Room 806, New York, NY 10010 USA.
FU NIDCR NIH HHS [DE10593-S1]
NR 41
TC 9
Z9 9
U1 0
U2 2
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 FAL
PY 2001
VL 61
IS 4
BP 203
EP 209
DI 10.1111/j.1752-7325.2001.tb03392.x
PG 7
WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational
   Health
SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational
   Health
GA 507MW
UT WOS:000173033100003
PM 11822112
ER

PT J
AU Weaver, K
   Price, R
   Czerniecki, J
   Sangeorzan, B
AF Weaver, K
   Price, R
   Czerniecki, J
   Sangeorzan, B
TI Design and validation of an instrument package designed to increase the
   reliability of ankle range of motion measurements
SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT
LA English
DT Article
DE ankle; contracture; equinus; goniometer reliability
ID GONIOMETRIC MEASUREMENTS
AB Objective: To validate a novel device termed the equinometer, which is designed to accurately measure ankle dorsiflexion. Design: Test retest reliability analysis using serial measurements of dorsiflexion endpoint in a group of normal individuals, Setting: Motion analysis laboratory. Participants: Ten healthy individuals. Primary Outcome Measure: The mean and standard deviation of the absolute difference in dorsiflexion endpoint for the group. Results: The mean absolute change in dorsiflexion endpoint for the group was 0.45 degrees with a standard deviation of 0.43 degrees. Conclusions: With the use of the device described, the mean change in dorsiflexion endpoint was well within acceptable clinical limits. The reliability of measurements obtained with the equinometer exceeds that which has been published with other techniques and devices.
C1 Univ Washington, Harborview Med Ctr, Dept Rehabil Med, Seattle, WA 98104 USA.
   Univ Washington, Med Ctr, Seattle, WA 98195 USA.
   VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Weaver, K (reprint author), Univ Washington, Harborview Med Ctr, Dept Rehabil Med, 325 9th Ave,Box 359740, Seattle, WA 98104 USA.
NR 16
TC 12
Z9 12
U1 0
U2 2
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 SEP-OCT
PY 2001
VL 38
IS 5
BP 471
EP 475
PG 5
WC Rehabilitation
SC Rehabilitation
GA 493WZ
UT WOS:000172247600004
PM 11732825
ER

PT J
AU Henry, JA
   Flick, CL
   Gilbert, A
   Ellingson, RM
   Fausti, SA
AF Henry, JA
   Flick, CL
   Gilbert, A
   Ellingson, RM
   Fausti, SA
TI Comparison of two computer-automated procedures for tinnitus pitch
   matching
SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT
LA English
DT Article
DE hearing disorders; pitch perception; reliability of results; tinnitus
AB Clinical assessment of the perceptual characteristics of tinnitus usually includes an attempt to match the pitch of tinnitus to a pure tone. A standardized clinical protocol for tinnitus pitch matching does not yet exist, and there is a history of unsuccessful attempts to obtain such measures reliably. The present study was designed to evaluate new protocols for identifying the perceived pitch of tinnitus, with the objectives of reducing testing time and improving test-retest reliability. Two protocols ("Octave" and "Binary") were developed, each of which was patterned after the testing procedure previously developed at the Oregon Tinnitus Clinic and used to assess thousands of tinnitus patients. Both protocols use computer-automation to conduct testing; the protocols differ according to their specific testing algorithms. Twenty subjects with nonfluctuating tinnitus were each tested over two sessions. Results of testing revealed that both protocols could obtain pitch matches within 20 to 25 min. Reliability of responses was good for some subjects but not others, and the Binary protocol generally provided more reliable results.
C1 Portland VA Med Ctr, NCRAR, VA Rehabil Res & Dev, Portland, OR 97207 USA.
   Oregon Hlth Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA.
RP Henry, JA (reprint author), Portland VA Med Ctr, NCRAR, VA Rehabil Res & Dev, POB 1034, Portland, OR 97207 USA.
NR 22
TC 20
Z9 21
U1 1
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 SEP-OCT
PY 2001
VL 38
IS 5
BP 557
EP 566
PG 10
WC Rehabilitation
SC Rehabilitation
GA 493WZ
UT WOS:000172247600012
PM 11732833
ER

PT J
AU Henry, JA
   Flick, CL
   Gilbert, A
   Ellingson, RM
   Fausti, SA
AF Henry, JA
   Flick, CL
   Gilbert, A
   Ellingson, RM
   Fausti, SA
TI Reliability of hearing thresholds: Computer-automated testing with ER-4B
   canal Phone (TM) earphones
SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT
LA English
DT Article
DE auditory; threshold; hearing; reliability of results
ID HIGH-FREQUENCY AUDIOMETRY; INSERT EARPHONES; ADULTS; ATTENUATION;
   VARIABILITY
AB This study was conducted to document test-retest reliability of hearing thresholds using our computer-automated tinnitus matching technique and Etymotic ER-4B Canal Phone (TM) insert earphones. The research design involved repeated threshold measurements both within and between sessions, and testing to evaluate the potential effect of eartip removal and reinsertion. Twenty normal-hearing subjects were evaluated over two testing sessions with the use of a fully automated ;protocol for determining thresholds with 1-dB precision. Thresholds were first obtained at 0.5-16.0 kHz, in one-third octave frequency steps (16 test frequencies). The octave frequencies were then retested, first without removing the eartips, then after eartip removal and replacement. Responses between sessions differed by an average of 2.5 dB across all 16 test frequencies, and 91.5 percent of the repeated thresholds varied within +/-5 dB (98.1 percent within +/- 10 dB). Reliability of within-sessions thresholds was also good, and there was no effect of eartip removal and replacement.
C1 Portland VA Med Ctr, Natl VA Rehabil Res & Dev Ctr Rehabilitat Auditor, Portland, OR USA.
   Oregon Hlth Sci Univ, Dept Otolaryngol, Portland, OR 97201 USA.
RP Henry, JA (reprint author), VA Med Ctr, NCRAR, RR&D Ctr Rehabil Auditory Res, POB 1034, Portland, OR 97207 USA.
NR 60
TC 16
Z9 16
U1 1
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 SEP-OCT
PY 2001
VL 38
IS 5
BP 567
EP 581
PG 15
WC Rehabilitation
SC Rehabilitation
GA 493WZ
UT WOS:000172247600013
PM 11732834
ER

PT J
AU Koerner, F
   Oyama, T
   Kurosumi, M
   Maluf, H
AF Koerner, F
   Oyama, T
   Kurosumi, M
   Maluf, H
TI Ovarian hormone receptors in human mammary stromal cells
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE estrogen receptors; progesterone receptors; fibroblast; adipocyte;
   breast
ID ESTROGEN-RECEPTOR; HUMAN-BREAST; PROGESTERONE RECEPTORS; ADIPOSE-TISSUE;
   GLAND; IDENTIFICATION; EXPRESSION; ALPHA; GENE; BETA
AB Mesenchymal cells of the rodent breast express both estrogen and progesterone receptors. Searches for these molecules in the human breast have yielded conflicting results. Following immunohistochemical staining of samples of normal human breast tissue, the authors detected estrogen receptor cc protein and progesterone receptor protein in extralobular (non-specialized) fibroblasts and estrogen receptor a protein in adipocytes. Tissues from young teenage girls and pregnant women contained the greatest number of receptor positive fibroblasts. These observations confirm prior reports of the presence of ovarian hormone receptors in mammary fibroblasts. The findings also illustrate similarities in the organization of the rodent and human breasts and thereby suggest that regulation of the gland by ovarian hormones involves similar mechanisms in both species. (C) 2001 Published by Elsevier Science Ltd.
C1 Harvard Univ, Sch Med, Dept Pathol,James Homer Wright Lab Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Gunma Univ Hosp, Sch Med, Dept Pathol 2, Pathol Lab, Gunma, Japan.
   Saitama Canc Ctr Hosp, Dept Clin Pathol, Saitama, Japan.
   Univ Washington, Sch Med, Barnes Hosp, Lauren V Ackerman Lab Pathol,Div Surg Pathol, Seattle, WA USA.
RP Koerner, F (reprint author), Harvard Univ, Sch Med, Dept Pathol,James Homer Wright Lab Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 17
TC 9
Z9 11
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD SEP
PY 2001
VL 78
IS 3
BP 285
EP 290
DI 10.1016/S0960-0760(01)00095-4
PG 6
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 487XP
UT WOS:000171904800009
PM 11595509
ER

PT J
AU Maisto, SA
   Conigliaro, J
   McNeil, M
   Kraemer, K
   Conigliaro, RL
   Kelley, ME
AF Maisto, SA
   Conigliaro, J
   McNeil, M
   Kraemer, K
   Conigliaro, RL
   Kelley, ME
TI Effects of two types of brief intervention and readiness to change on
   alcohol use in hazardous drinkers
SO JOURNAL OF STUDIES ON ALCOHOL
LA English
DT Article
ID PRIMARY-CARE; SUBSTANCE-ABUSE; PHYSICIAN; DRINKING; CONSUMPTION;
   MOTIVATION; TRIALS; AUDIT; SCALE; RISK
AB Objective: Brief interventions for hazardous and low-dependent drinkers in the primary care setting have considerable empirical support. The purpose of this study was to (1) evaluate the effects of brief advice (BA) and motivational enhancement (ME) interventions on alcohol consumption. In addition, a hindsight matching design was used to (2) study the moderator effects of patient readiness to change (alcohol use) on alcohol consumption. Method: The subjects (N = 301, 70% men) were patients 21 years of age or older who presented for treatment at one of 12 primary care clinics. After screening for eligibility and providing consent to participate in the study, the patients completed a baseline assessment and were randomly assigned to the BA, ME or standard care (SC) interventions condition. Follow-up assessments were completed at 1-, 3-, 6-, 9- and 12-months postbaseline assessment. Results: Evaluation of the first hypothesis (n = 232 for these analyses) showed that all participants tended to reduce their alcohol use considerably between the baseline and 12-month assessments. In addition, evaluation of the second hypothesis showed a moderator effect of readiness to change in predicting the number of drinks at 12 months, such that the BA intervention seemed more effective for patients relatively low in readiness to change compared to those higher in readiness. Readiness to change did not seem to be related to changes in drinking of participants in the SC or ME conditions. Conclusions: The results confirm that, among primary care patients, substantial changes in alcohol consumption are possible. They further suggest that matching studies of patient readiness to change their alcohol use, as well as other variables, are warranted.
C1 Syracuse Univ, Ctr Hlth & Behav, Dept Psychol, Syracuse, NY 13244 USA.
   VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA.
   Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA.
RP Maisto, SA (reprint author), Syracuse Univ, Ctr Hlth & Behav, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA.
FU NIAAA NIH HHS [5K01-AA00235, AA1029]
NR 36
TC 61
Z9 61
U1 12
U2 15
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 0096-882X
J9 J STUD ALCOHOL
JI J. Stud. Alcohol
PD SEP
PY 2001
VL 62
IS 5
BP 605
EP 614
PG 10
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA 485BP
UT WOS:000171733900008
PM 11702799
ER

PT J
AU Voss, SE
   Rosowski, JJ
   Merchant, SN
   Peake, WT
AF Voss, SE
   Rosowski, JJ
   Merchant, SN
   Peake, WT
TI Middle-ear function with tympanic-membrane perforations. I. Measurements
   and mechanisms
SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
LA English
DT Article
ID TYMPANOSTOMY TUBES; INPUT IMPEDANCE; EARPHONES; CAT
AB Sound transmission through ears with tympanic-membrane (TM) perforations is not well understood. Here. measurements on human-cadaver ears are reported that describe sound transmission through the middle ear with experimentally produced perforations, which range from 0.5 to 5.0 mm in diameter. Three response variables were measured with acoustic stimulation at the TM: stapes velocity, middle-ear cavity sound pressure, and acoustic impedance at the TM. The stapes-velocity measurements show that perforations cause frequency-dependent losses; at low frequencies losses are largest and increase as perforation size increases. Measurements of middle-ear cavity pressure coupled with the stapes-velocity measurements indicate that the dominant mechanism for loss with TM perforations is reduction in pressure difference across the TM; changes in TM-to-ossicular coupling generally contribute less than 5 dB to the loss. Measurements of middle-ear input impedance indicate that for low frequencies. the input impedance with a perforation approximates the impedance of the middle-ear cavity; as the perforation size increases, the similarity to the cavity's impedance extends to higher frequencies. The collection of results suggests that the effects of perforations can be represented by the path for air-volume flow from the ear canal to the middle-car cavity. The quantitative description of perforation-induced losses may help clinicians determine, in an ear with a perforation, whether poor hearing results only from the perforation or whether other pathology should be expected. (C) 2001 Acoustical Society of America.
C1 Smith Coll, Picker Engn Program, Northampton, MA 01063 USA.
   Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA.
   Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
   Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA.
   Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
   MIT, Elect Res Lab, Cambridge, MA 02139 USA.
   MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
   MIT, Elect Res Lab, Cambridge, MA 02139 USA.
RP Voss, SE (reprint author), Smith Coll, Picker Engn Program, 51 Coll Lane, Northampton, MA 01063 USA.
NR 43
TC 43
Z9 48
U1 2
U2 8
PU AMER INST PHYSICS
PI MELVILLE
PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA
SN 0001-4966
J9 J ACOUST SOC AM
JI J. Acoust. Soc. Am.
PD SEP
PY 2001
VL 110
IS 3
BP 1432
EP 1444
DI 10.1121/1.1394195
PN 1
PG 13
WC Acoustics; Audiology & Speech-Language Pathology
SC Acoustics; Audiology & Speech-Language Pathology
GA 471XH
UT WOS:000170953600024
PM 11572354
ER

PT J
AU Voss, SE
   Rosowski, JJ
   Merchant, SN
   Peake, WT
AF Voss, SE
   Rosowski, JJ
   Merchant, SN
   Peake, WT
TI Middle-ear function with tympanic-membrane perforations. II. A simple
   model
SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
LA English
DT Article
ID ACOUSTIC MECHANISMS; EARPHONES
AB A quantitative model of the human middle ear with a tympanic-membrane (TM) perforation is developed. The model is constrained by several types of acoustic measurements made on human cadaver ears, which indicate that perforation-induced changes in transmission result primarily from changes in driving pressure across the TM and that perforation-induced change in the structure of the TM and its coupling to the ossicles contributes a substantially smaller component. The model represents the effect of a perforation on the pressure difference across the TM by inclusion of a path for sound coupling through the perforation from the ear canal to the middle-ear cavity. The model implies that hearing loss with perforations depends primarily on three quantities: the perforation diameter, sound frequency, and the volume of air in the middle-car cavity. For the conditions that produce the largest hearing loss (low frequency and large perforation), the model yields a simple dependence of loss on frequency, perforation diameter, and middle-ear cavity volume. Predictions from this model may be useful to clinicians in determining whether, in particular cases, hearing losses are explainable by the observed perforations or if additional pathology must be involved. (C) 2001 Acoustical Society of America.
C1 Smith Coll, Picker Engn Program, Northampton, MA 01063 USA.
   Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA.
   Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
   Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA.
   Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
   MIT, Elect Res Lab, Cambridge, MA 02139 USA.
RP Voss, SE (reprint author), Smith Coll, Picker Engn Program, 51 Coll Lane, Northampton, MA 01063 USA.
NR 24
TC 23
Z9 28
U1 0
U2 4
PU AMER INST PHYSICS
PI MELVILLE
PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA
SN 0001-4966
J9 J ACOUST SOC AM
JI J. Acoust. Soc. Am.
PD SEP
PY 2001
VL 110
IS 3
BP 1445
EP 1452
DI 10.1121/1.1394196
PN 1
PG 8
WC Acoustics; Audiology & Speech-Language Pathology
SC Acoustics; Audiology & Speech-Language Pathology
GA 471XH
UT WOS:000170953600025
PM 11572355
ER

PT J
AU Langley, RGB
   Rajadhyaksha, M
   Dwyer, PJ
   Sober, AJ
   Flotte, TJ
   Anderson, RR
AF Langley, RGB
   Rajadhyaksha, M
   Dwyer, PJ
   Sober, AJ
   Flotte, TJ
   Anderson, RR
TI Confocal scanning laser microscopy of benign and malignant melanocytic
   skin lesions in vivo
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
ID INVIVO EPILUMINESCENCE MICROSCOPY; CLINICAL-DIAGNOSIS; IN-VIVO; MELANOMA
AB Background: The ability of physicians for early diagnosis of cutaneous melanomas is less than perfect, prompting research into noninvasive methods for diagnosis.
   Objective: Our purpose was to evaluate confocal scanning laser microscopy (CSLM) for noninvasive imaging of benign and malignant melanocytic lesions in vivo.
   Methods: Forty pigmented skin lesions (including adjacent normal skin as control) in vivo were imaged with near-infrared CSLM. The confocal images were correlated to histopathology.
   Results: Nuclear, cellular, and architectural detail in the epidermis and-superficial dermis is imaged with high resolution and contrast. Melanin causes the cytoplasm of pigmented cells to appear bright. Melanocytic nevi had cohesive nests of uniformly circular cells and increased microvascular blood flown Melanomas had a polymorphous cytologic structure, containing atypical, pleomorphic cells in disarray and irregular dendritic cells.
   Conclusion: CSLM is capable of identifying distinct patterns and cytologic features of benign and malignant pigmented skin lesions in vivo. CSLM maybe useful to noninvasively discriminate benign and malignant lesions in vivo.
C1 Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
   Harvard Univ, Sch Med, Dermatopathol Unit, Wellman Labs Photomed,Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
RP Langley, RGB (reprint author), QEII Hlth Sci Ctr, Dept Med, Div Dermatol, 1278 Tower Rd,4195 Dickson Bldg, Halifax, NS B3H 1V8, Canada.
NR 13
TC 139
Z9 149
U1 2
U2 3
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 SEP
PY 2001
VL 45
IS 3
BP 365
EP 376
DI 10.1067/mjd.2001.117395
PG 12
WC Dermatology
SC Dermatology
GA 468TC
UT WOS:000170773400002
PM 11511832
ER

PT J
AU Steinbacher, DM
   Glick, M
AF Steinbacher, DM
   Glick, M
TI The dental patient with asthma - An update and oral health
   considerations
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Article
ID SALIVARY FLOW-RATE; BETA-2-ADRENOCEPTOR AGONISTS; NONASTHMATIC ADULTS;
   SULFITE SENSITIVITY; CARIES DEVELOPMENT; CHILDREN; THERAPY; GROWTH;
   IMMUNOTHERAPY; TECHNICIANS
AB Overview. Asthma is a serious global health problem that has steadily increased in prevalence during the past two decades. New classification and treatment guidelines have been published, and dental providers need to be aware of these, changes.
   Literature Reviewed. The authors searched textbooks and MEDLINE looking Or the most updated medical information. on asthma, as well as for previous, publications on treatment of asthmatic patients in a dental setting.
   Results. More than 9,000 articles on asthma were published in English,between 1997 and 2000. From 1960 until 2000, approximately 40 articles specifically addressed asthma. and dental care. The authors reviewed more than 300 articles om the medical literature and all articles. after 1980 that directly focused on oral health issues for importance and relevance.
   Conclusions. Recent information regarding the etiology, pathogenesis and treatment of asthma had not been adequately addressed in the dental literature. Dental care of asthmatic patients may considerations beyond what was previously been published in the dental literature.
   Clinical Implications. In the treatment of asthma, as with treatment of most medical conditions, oral health care providers play a role that is important in terms of both the patient's overall health and the systemic condition's effect on oral health. This article provides dentists with a timely update-on-asthma-a-nd the relation between asthma and oral health, and it offers suggestions for safe and appropriate dental care.
C1 Univ Penn, Sch Dent Med, Programs Med Complex Patients, Philadelphia, PA 19104 USA.
   Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
RP Steinbacher, DM (reprint author), Univ Penn, Sch Dent Med, Programs Med Complex Patients, Philadelphia, PA 19104 USA.
NR 82
TC 21
Z9 24
U1 1
U2 13
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 SEP
PY 2001
VL 132
IS 9
BP 1229
EP 1239
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 474FV
UT WOS:000171096400016
PM 11665347
ER

PT J
AU Delahanty, LM
   Sonnenberg, LM
   Hayden, D
   Nathan, DM
AF Delahanty, LM
   Sonnenberg, LM
   Hayden, D
   Nathan, DM
TI Clinical and cost outcomes of medical nutrition therapy for
   hypercholesterolemia: A controlled trial
SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION
LA English
DT Article
ID DENSITY-LIPOPROTEIN CHOLESTEROL; SERUM-CHOLESTEROL; HDL-CHOLESTEROL;
   HEART-DISEASE; DIET; PROGRAM; ASSAY; MEN
AB Objective To compare the results and cost-effectiveness of a cholesterol lowering protocol implemented by registered dietitians with cholesterol lowering advice by physicians.
   Design Six month randomized controlled trial, cost-effectiveness analysis. Subjects included 90 ambulatory care patients (60 men, 30 women), age range 21 to 65 years, with hypercholesterolemia and not taking hypolipidemic drugs. Patients were randomly assigned to receive medical nutrition therapy (MNT) from dietitians using a NCEP based lowering protocol or usual care (UC) from physicians. Outcome measures were plasma lipid profiles, dietary intake, weight, activity, patient satisfaction, and costs of MNT. Changes from baseline for each variable of interest were compared between treatment groups using analysis of covariance controlling for baseline value of the variable and gender.
   Results MNT achieved a 6% decrease in total and LDL cholesterol levels at 3 and 6 months compared with a 1% increase and a 2% decrease in both values at 3 and 6 months with UC (P < .001 and P < .05, respectively). Weight loss (1.9 vs 0 kg, P < .001) and dietary intake of saturated fat (7% of energy vs 10%, P < .001) were better in the MNT than the UC group. The additional costs of MNT were $217 per patient to achieve a 6% reduction in cholesterol and $98 per patient to sustain the reduction. The cost-effectiveness ratio for MNT was $36 per 1% decrease in cholesterol and LDL level.
   Applications/conclusions MNT from registered dietitians is a reasonable investment of resources because it results in significantly better lipid, diet, activity, weight, and patient satisfaction outcomes than UC.
C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Ambulatory Nutr Serv, Boston, MA 02114 USA.
RP Delahanty, LM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St,Suite 340, Boston, MA 02114 USA.
FU NCRR NIH HHS [M01RR01066]
NR 26
TC 48
Z9 49
U1 0
U2 1
PU AMER DIETETIC ASSOC
PI CHICAGO
PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA
SN 0002-8223
J9 J AM DIET ASSOC
JI J. Am. Diet. Assoc.
PD SEP
PY 2001
VL 101
IS 9
BP 1012
EP +
DI 10.1016/S0002-8223(01)00250-4
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 499BW
UT WOS:000172552000014
PM 11573752
ER

PT J
AU Ramos, LR
   Simoes, EJ
   Albert, MS
AF Ramos, LR
   Simoes, EJ
   Albert, MS
TI Dependence in activities of daily living and cognitive impairment
   strongly predicted mortality in older urban residents in Brazil: A
   2-year follow-up
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the
   American-Geriatrics-Society/American-Federation-for-Aging-Research
CY MAY 06-10, 1998
CL SEATTLE, WASHINGTON
SP Amer Geriatr Soc, Amer Federat Aging Res
DE mortality rate; risk factors; dependence on daily living; cognitive
   status; functional capacity; older residents
ID SELF-RATED HEALTH; HOUSEHOLD SURVEY; ELDERLY PEOPLE; SURVIVAL;
   POPULATION; DECLINE; COUNTY; ADULTS; COHORT; RISK
AB OBJECTIVES: To identify a set of predictors of mortality among residents in the community, before any physical, biochemical, or image examination is performed, that could be collected on a routine standardized basis, to help the clinician define a patient follow-up strategy and the health planner make decisions regarding the care of older people.
   DESIGN: A household follow-up study, with an evaluation at baseline and 2 years later.
   SETTING: Residential area, with a low rate of in- and outmigration, in Sao Paulo a large industrialized urban center in southeastern Brazil.
   PARTICIPANTS: One thousand six hundred sixty-seven older urban residents in the community (65+), from different socioeconomic backgrounds, enrolled after a study area census.
   INTERVENTION: Structured home interview with Brazilian Older Americans Resources and Services Multidimensional Functional Assessment Questionnaire, previously validated in Portuguese.
   MEASUREMENTS: A logistic regression model for the risk of dying in the period was developed, having as independent variables, sociodemographic characteristics plus six other dimensions: subjective self-evaluation of health, past medical history, use of health services, dependence in activities of daily living (ADLs), mental health, and cognitive status.
C1 Univ Fed Sao Paulo, Div Geriatr, Ctr Study Aging, Sao Paulo, Brazil.
   Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
   St Louis Univ, Missouri Dept Hlth, Div Chron Dis Prevent & Hlth Promot, St Louis, MO 63103 USA.
   St Louis Univ, Sch Publ Hlth, St Louis, MO 63103 USA.
RP Ramos, LR (reprint author), UNIFESP EPM, Ctr Estudos Envelhecimento, Rua Ottonis 731, BR-04025002 Sao Paulo, SP, Brazil.
RI Ramos, Luiz/E-5343-2012; 
OI Simoes, Eduardo/0000-0003-4371-4305
NR 43
TC 72
Z9 94
U1 3
U2 9
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 SEP
PY 2001
VL 49
IS 9
BP 1168
EP 1175
DI 10.1046/j.1532-5415.2001.49233.x
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 474DR
UT WOS:000171090700005
PM 11559375
ER

PT J
AU Hazzard, WR
AF Hazzard, WR
TI Depressed albumin and high-density lipoprotein cholesterol: Signposts
   along the final common pathway of frailty
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Editorial Material
ID INFLAMMATION; DISEASE
C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Hazzard, WR (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA.
NR 7
TC 16
Z9 16
U1 0
U2 3
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 SEP
PY 2001
VL 49
IS 9
BP 1253
EP 1254
DI 10.1046/j.1532-5415.2001.49245.x
PG 2
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 474DR
UT WOS:000171090700018
PM 11559388
ER

PT J
AU Lovis, C
   Chapko, MK
   Martin, DP
   Payne, TH
   Baud, RH
   Hoey, PJ
   Fihn, SD
AF Lovis, C
   Chapko, MK
   Martin, DP
   Payne, TH
   Baud, RH
   Hoey, PJ
   Fihn, SD
TI Evaluation of a command-line parser-based order entry pathway for the
   Department of Veterans Affairs electronic patient record
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID SYSTEM; SATISFACTION; LEGIBILITY; PHYSICIANS; STUDENTS; IMPACT; ERRORS;
   TIME; TEXT
AB Objective: To improve and simplify electronic order entry in an existing electronic patient record, the authors developed an alternative system for entering orders, which is based on a command-line interface using robust and simple natural-language techniques.
   Design: The authors conducted a randomized evaluation of the new entry pathway, measuring time to complete a standard set of orders, and users' satisfaction measured by questionnaire. A group of 16 physician volunteers from the staff of the Department of Veterans Affairs Puget Sound Health Care System-Seattle Division participated in the evaluation.
   Results: Thirteen of the 16 physicians (81 %) were able to enter medical orders more quickly using the natural-language-based entry system than the standard graphical user interface that uses menus and dialogs (mean time spared, 16.06 +/- 4.52 minutes; P = 0.029). Compared with the graphical user interface, the command-line-based pathway was perceived as easier to learn (P < 0.01), was considered easier to use and faster (P < 0.01), and was rated better overall (P < 0.05).
   Conclusion: Physicians found the command-line interface easier to learn and faster to use than the usual menu-driven system. The major advantage of the system is that it combines an intuitive graphical user interface with the power and speed of a natural-language analyzer.
C1 Univ Hosp Geneva, Div Med Informat, Integrated Elect Patient Record Grp, CH-1211 Geneva 4, Switzerland.
   Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
   Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Lovis, C (reprint author), Univ Hosp Geneva, Div Med Informat, Integrated Elect Patient Record Grp, 21 Micheli du Crest, CH-1211 Geneva 4, Switzerland.
RI Lovis, Christian/D-2634-2012
OI Lovis, Christian/0000-0002-2681-8076
NR 33
TC 16
Z9 16
U1 1
U2 2
PU HANLEY & BELFUS INC
PI PHILADELPHIA
PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD SEP-OCT
PY 2001
VL 8
IS 5
BP 486
EP 498
PG 13
WC Computer Science, Information Systems; Computer Science,
   Interdisciplinary Applications; Information Science & Library Science;
   Medical Informatics
SC Computer Science; Information Science & Library Science; Medical
   Informatics
GA 473GC
UT WOS:000171031300007
PM 11522769
ER

PT J
AU Prelack, K
   Sheridan, RL
AF Prelack, K
   Sheridan, RL
TI Micronutrient supplementation in the critically ill patient: Strategies
   for clinical practice
SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE
LA English
DT Review
ID RETINOL-BINDING-PROTEIN; VITAMIN-A-DEFICIENCY;
   RESPIRATORY-DISTRESS-SYNDROME; TOTAL PARENTERAL-NUTRITION; ENDOGENOUS
   MEDIATOR LEM; URINARY ZINC EXCRETION; ACUTE-PHASE RESPONSE;
   THERMAL-INJURY; LIPID-PEROXIDATION; CONTROLLED-TRIAL
C1 Massachusetts Gen Hosp, Burn Serv, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Trauma Serv, Boston, MA 02114 USA.
   Shriners Hosp Children, Boston, MA USA.
   Tufts Univ, Boston, MA 02111 USA.
   Harvard Univ, Boston, MA 02115 USA.
RP Sheridan, RL (reprint author), Massachusetts Gen Hosp, Burn Serv, MGH-GRB 1302,55 Fruit St, Boston, MA 02114 USA.
NR 170
TC 12
Z9 14
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5282
EI 1529-8809
J9 J TRAUMA
JI J. Trauma-Injury Infect. Crit. Care
PD SEP
PY 2001
VL 51
IS 3
BP 601
EP 620
DI 10.1097/00005373-200109000-00037
PG 20
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA 471WW
UT WOS:000170952500038
PM 11535921
ER

PT J
AU Bromley, B
   Roberts, DJ
   Tracy, EE
   Greene, MF
   Shipp, TD
   Benacerraf, BR
AF Bromley, B
   Roberts, DJ
   Tracy, EE
   Greene, MF
   Shipp, TD
   Benacerraf, BR
TI Fibroepithelial bladder polyp and renal tubular dysgenesis - An unusual
   cause of third-trimester oligohydramnios
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Article
ID SIBLINGS; FETAL; ONSET
C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA USA.
   Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynec, Boston, MA USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA USA.
   Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Womens & Perinatal Pathol,Dept Pathol, Boston, MA USA.
RP Bromley, B (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA.
NR 13
TC 2
Z9 2
U1 0
U2 0
PU AMER INST ULTRASOUND MEDICINE
PI LAUREL
PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906
   USA
SN 0278-4297
J9 J ULTRAS MED
JI J. Ultrasound Med.
PD SEP
PY 2001
VL 20
IS 9
BP 1015
EP 1019
PG 5
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA 467TA
UT WOS:000170718800013
PM 11549150
ER

PT J
AU Weissman, JS
   Campbell, EG
   Gokhale, M
   Blumenthal, D
AF Weissman, JS
   Campbell, EG
   Gokhale, M
   Blumenthal, D
TI Residents' preferences and preparation for caring for underserved
   populations
SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE
LA English
DT Article
ID MARKET COMPETITION; MEDICAL-EDUCATION; INTERNAL-MEDICINE; PHYSICIANS
   VIEWS; UNITED-STATES; CARE; VIOLENCE; FACULTY; SERVICE; RACE
AB Access to care by low-income persons and residents of rural and poor inner-city areas is a persistent Problem, yet Physicians tend to be maldistributed relative to need. The objectives were to describe preferences of resident physicians to locate in underserved areas and to assess their preparedness to provide service to low-income populations. A national survey was made of residents completing their training in eight specialties at 162 US academic health center hospitals in 1998, with 2,626 residents responding. (Of 4,832 sampled, 813 had invalid addresses or were no longer in the residency program. Among the valid sample of 4,019, the response rate was 65%.) The percentage of residents ranking public hospitals, rural areas, and poor inner-city areas as desirable employment locations and the Percentage feeling prepared to provide specified services associated with indigent populations were ascertained. Logistic regressions were used to calculate adjusted percentages, controlling for sex, race/ethnicity, international medical graduate (IMG) status, plans to subspecialize, ownership of hospital, specialty, and exposure to underserved patients during residency. Only, one third of residents rated public hospitals as desirable settings, although there were large variations by specialty. Desirability was not associated with having trained in a public hospital or having greater exposure to underserved populations. Only about one quarter of respondents ranked rural (26%) or poor inner-city (25%) areas as desirable. Men (29%, P<.01) and noncitizen IMGs (43%, P<.01)were more likely than others to prefer rural settings. Residents who were more likely to rate poor inner-city settings as desirable included women (28%, P=.03), noncitizen IMGS (35%, P=.01), and especially underrepresented minorities (52%, P<.01). Whereas about 90% or more of residents felt prepared to treat common clinical conditions, only 67% of residents in four primary care specialties felt prepared to counsel patients about domestic violence or to care for human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) or substance abuse patients (all 67%). Women were more likely than men to feel prepared to counsel patients about domestic violence (70% vs. 63%, P=.002) and depression (83% vs. 75%, P<.01). Underrepresented minority residents were more likely than other residents to feel prepared to counsel patients about domestic violence (P<.01) and compliance with care (P=.04). Residents with greater exposure to underserved groups were more prepared to counsel patients about domestic violence (P=.01), substance abuse (P=.01), and to treat patients with HIV/AIDS (P=.01) or with substance abuse problems (P<.01). This study demonstrates the need to expose graduate trainees to underserved populations and suggests a continuing role of minorities, women, and noncitizen physicians in caring for low-income populations.
C1 Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
   Partners Healthcare Syst, Boston, MA 02199 USA.
   Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA.
RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
NR 41
TC 34
Z9 34
U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1099-3460
J9 J URBAN HEALTH
JI J. Urban Health
PD SEP
PY 2001
VL 78
IS 3
BP 535
EP 549
DI 10.1093/jurban/78.3.535
PG 15
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 471GF
UT WOS:000170919900011
PM 11564855
ER

PT J
AU Zietman, AL
AF Zietman, AL
TI High dose radiation delivered by intensity modulated conformal
   radiotherapy improves the outcome of localized prostate cancer -
   Editorial comment
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA.
NR 2
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD SEP
PY 2001
VL 166
IS 3
BP 881
EP 881
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 463AA
UT WOS:000170453600020
ER

PT J
AU Barry, MJ
AF Barry, MJ
TI Patient reported complications after prostate brachytherapy - Editorial
   comment
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
ID OUTCOMES; CANCER
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 2
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-5347
J9 J UROLOGY
JI J. Urol.
PD SEP
PY 2001
VL 166
IS 3
BP 957
EP 957
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA 463AA
UT WOS:000170453600042
ER

PT J
AU Nakajima, N
   Lu, R
   Engelman, A
AF Nakajima, N
   Lu, R
   Engelman, A
TI Human immunodeficiency virus type 1 replication in the absence of
   integrase-mediated DNA recombination: Definition of permissive and
   nonpermissive T-Cell lines
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LONG TERMINAL REPEAT; STRUCTURE-BASED MUTAGENESIS; HIV-1 TAT PROTEIN;
   GENE-EXPRESSION; PRODUCTIVE INFECTION; VIRAL REPLICATION;
   MAMMALIAN-CELLS; HIGH-TITER; IN-VIVO; ACTIVATION
AB Functional retroviral integrase protein is thought to be essential for productive viral replication. Yet, previous studies differed on the extent to which integrase mutant viruses expressed human immunodeficiency virus type 1 (HIV-1) genes from unintegrated DNA. Although one reason for this difference was that class II integrase mutations pleiotropically affected the viral life cycle, another reason apparently depended on the identity of the infected cell. Here, we analyzed integrase mutant viral infectivities in a variety of cell types. Single-round infectivity of class I integration-specific mutant HIV-1 ranged from <0.03 to 0.3% of that of the wild type (WT) across four different T-cell lines. Based on this approximately 10-fold influence of cell type on mutant gene expression, we examined class I and class II mutant replication kinetics in seven different cell lines and two primary cell types. Unexpectedly, some cell lines supported productive class I mutant viral replication under conditions that restricted class II mutant growth. Cells were defined as permissive, semipermissive, or nonpermissive based on their ability to support the continual passage of class I integration-defective HIV-1. Mutant infectivity in semipermissive and permissive cells as quantified by 50% tissue culture infectious doses, however, was only 0.0006 to 0.005% of that of WT. Since the frequencies of mutant DNA recombination in these lines ranged from 0.023 to <0.093% of the WT, we conclude that productive replication in the absence of integrase function most likely required the illegitimate integration of HIV-1 into host chromosomes by cellular DNA recombination enzymes.
C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA.
FU NIAID NIH HHS [AI45313]
NR 62
TC 72
Z9 73
U1 0
U2 1
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 SEP
PY 2001
VL 75
IS 17
BP 7944
EP 7955
DI 10.1128/JVI.75.17.7944-7955.2001
PG 12
WC Virology
SC Virology
GA 461AZ
UT WOS:000170343900018
PM 11483739
ER

PT J
AU Geiben-Lynn, R
   Kursar, M
   Brown, NV
   Kerr, EL
   Luster, AD
   Walker, BD
AF Geiben-Lynn, R
   Kursar, M
   Brown, NV
   Kerr, EL
   Luster, AD
   Walker, BD
TI Noncytolytic inhibition of X4 virus by bulk CD8(+) cells from human
   immunodeficiency virus type 1 (HIV-1)-Infected persons and
   HIV-1-Specific cytotoxic T lymphocytes is not mediated by
   beta-chemokines
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HIV-1 INFECTION; REVERSE TRANSCRIPTION; FINE SPECIFICITY; CC-CHEMOKINE;
   SUPPRESSION; REPLICATION; LESTR/FUSIN; INDIVIDUALS; RESISTANCE;
   EXPRESSION
AB Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) mediate immunologic selection pressure by both cytolytic and noncytolytic mechanisms. Non cytolytic mechanisms include the release of beta -chemokines blocking entry of R5 HIV-1 strains. In addition, CD8(+) cells inhibit X4 virus isolates via release of as yet poorly characterized soluble factors. To further characterize these factors, we performed detailed analysis of CTL as well as bulk CD8+ T lymphocytes from six HIV-1-infected individuals and from six HIV-1-seronegative individuals. Kinetic studies revealed that secreted suppressive activities of HIV-1-specific CTL and bulk CD8(+) T lymphocytes from all HIV-1-infected persons are significantly higher than that of supernatants from seronegative controls. The suppressive activity could be blocked by monensin and brefeldin A, was heat labile, and appeared in a pattern different from that of secretion of chemokines (MDC, I-309, MIP-1 alpha, MIP-1 beta, and RANTES), cytokines (gamma interferon, tumor necrosis factor alpha, and granulocytemacrophage colony-stimulating factor), and interleukins (interleukin-13 and interleukin-16). This suppression activity was characterized by molecular size exclusion centrifugation and involves a suppressive activity of > 50 kDa which could be bound to heparin and a nonbinding inhibitory activity of < 50 kDa. Our data provide a functional link between CD8(+) cells and CTL in the noncytolytic inhibition of HIV-1 and suggest that suppression of X4 virus is mediated through proteins. The sizes of the proteins, their affinity for heparin, and the pattern of release indicate that these molecules are not chemokines.
C1 Partners AIDS Res Ctr, Charlestown, MA 02129 USA.
   Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA.
   Harvard Univ, Sch Med, Boston, MA 02129 USA.
RP Walker, BD (reprint author), Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA.
FU NIAID NIH HHS [R37 AI028568, AI46999, AI30914, AI28568, R01 AI028568,
   R01 AI030914, R01 AI046999]
NR 39
TC 31
Z9 31
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 SEP
PY 2001
VL 75
IS 17
BP 8306
EP 8316
DI 10.1128/JVI.75.17.8306-8316.2001
PG 11
WC Virology
SC Virology
GA 461AZ
UT WOS:000170343900055
PM 11483776
ER

PT J
AU Holmberg, EB
   Hillman, RE
   Hammarberg, B
   Sodersten, M
   Doyle, P
AF Holmberg, EB
   Hillman, RE
   Hammarberg, B
   Sodersten, M
   Doyle, P
TI Efficacy of a behaviorally based voice therapy protocol for vocal
   nodules
SO JOURNAL OF VOICE
LA English
DT Article
DE efficacy; voice therapy; vocal nodules; perceptual evaluations; voice
   quality
ID IMPACT STRESS; AIR-FLOW; QUALITY; PRESSURE; PERCEPTION; PHONATION;
   FRAMEWORK; FEMALE
AB The aim of this study was to assess the effects on vocal function of voice therapy for vocal nodules. Perceptual and physiological progressive changes were examined during a strictly structured, behaviorally based voice therapy protocol in which I I women with vocal nodules participated. Randomized audio recordings from pretherapy and from each of the therapy approaches (vocal hygiene, respiration, direct facilitation, carryover) were used for perceptual evaluations. Six speech-language pathologists rated ten voice quality parameters. Two evaluation procedures were performed and compared. Inter-listener reliability was sufficiently high in both tests. Significant effects of therapy were found for decreased overall dysphonia, press, instability, gratings, roughness, vocal fry, and "scrape." Nonsignificant group effects were found for breathiness, aphonic instances, and lack of sonority. No significant parameter changes occurred between baseline assessment and the completion of the initial (vocal hygiene) phase of therapy. Significant changes were found following the direct facilitation and respiration phases of therapy. Video stroboscopic evaluations made by two laryngologists showed that in no case were the nodules completely resolved. However, the nodules had decreased in size and edema was reduced after therapy for all clients, but one. Combined results suggest: (1) Alterations in vocal function were reflected in perceptual parameters, and (2) the voice therapy had a positive effect on voice quality, vocal status, and vocal function for the majority of the vocal nodule clients.
C1 Huddinge Univ Hosp, Karolinska Inst, Dept Logoped & Phoniatr, SE-14186 Stockholm, Sweden.
   Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA.
   Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA.
RP Holmberg, EB (reprint author), Huddinge Univ Hosp, Karolinska Inst, Dept Logoped & Phoniatr, SE-14186 Stockholm, Sweden.
EM Eva.Holmberg@klinvet.ki.se
FU NIDCD NIH HHS [R01 DC00266-15]
NR 71
TC 76
Z9 79
U1 1
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0892-1997
J9 J VOICE
JI J. Voice
PD SEP
PY 2001
VL 15
IS 3
BP 395
EP 412
DI 10.1016/S0892-1997(01)00041-8
PG 18
WC Otorhinolaryngology
SC Otorhinolaryngology
GA 473PR
UT WOS:000171055000009
PM 11575636
ER

PT J
AU Milliken, N
   Freund, K
   Pregler, J
   Reed, S
   Carlson, K
   Derman, R
   Zerr, A
   Battistini, M
   Bowman, S
   Magnus, JH
   Sarto, GE
   Chambers, JT
   McLaughlin, M
AF Milliken, N
   Freund, K
   Pregler, J
   Reed, S
   Carlson, K
   Derman, R
   Zerr, A
   Battistini, M
   Bowman, S
   Magnus, JH
   Sarto, GE
   Chambers, JT
   McLaughlin, M
TI Academic models of clinical care for women: The National Centers of
   Excellence in Women's Health
SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE
LA English
DT Article
ID SEX
AB Between 1996 and 1999, 18 academic health centers were awarded the designation of National Center of Excellence (CoE) in Women's Health by the Office on Women's Health within the Department of Health and Human Services and were provided with seed monies to develop model clinical services for women. Although the model has evolved in various forms, core characteristics that each nationally designated CoE has adopted include comprehensive, women-friendly, women-focused, women-relevant, integrated, multidisciplinary care. The permanent success of these comprehensive clinical programs resides in the ability to garner support of leaders of the academic health centers who understand both the importance of multidisciplinary programs to the clinical care they provide women and the education they offer to the future providers of women's healthcare.
C1 Univ Calif San Francisco, San Francisco, CA 94143 USA.
   Boston Univ, Med Ctr, Boston, MA USA.
   Univ Calif Los Angeles, Los Angeles, CA USA.
   Univ Washington, Sch Med, Seattle, WA USA.
   Massachusetts Gen Hosp, Boston, MA 02114 USA.
   Univ Illinois, Chicago, IL USA.
   Indiana Univ, Indianapolis, IN 46204 USA.
   Univ Penn, Philadelphia, PA 19104 USA.
   Med Coll Penn & Hahnemann Univ, Philadelphia, PA USA.
   Tulane Univ, New Orleans, LA 70118 USA.
   Univ Wisconsin, Madison, WI USA.
   St Lukes Roosevelt Hosp, New York, NY 10025 USA.
   St Catherines Coll, Minneapolis, MN USA.
RP Milliken, N (reprint author), Univ Calif San Francisco, 505 Parnassus Ave,M1476, San Francisco, CA 94143 USA.
OI Freund, Karen/0000-0002-9049-5574
NR 23
TC 15
Z9 15
U1 0
U2 0
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 1524-6094
J9 J WOMEN HEALTH GEN-B
JI J. WOMENS HEALTH GENDER-BASED MED.
PD SEP
PY 2001
VL 10
IS 7
BP 627
EP 636
DI 10.1089/15246090152563506
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
   Medicine; Obstetrics & Gynecology; Women's Studies
GA 474MN
UT WOS:000171111200004
PM 11571092
ER

PT J
AU Bonds, DE
   Freedberg, KA
AF Bonds, DE
   Freedberg, KA
TI Cost-effectiveness of prenatal screening for postpartum thyroiditis
SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE
LA English
DT Article; Proceedings Paper
CT 21st Annual Meeting of the Society-of-General-Internal-Medicine
CY APR 23-25, 1998
CL CHICAGO, ILLINOIS
SP Soc Gen Internal Med
ID DEPENDENT DIABETES-MELLITUS; TERM FOLLOW-UP; DYSFUNCTION;
   AUTOANTIBODIES; DEPRESSION; ANTIBODIES; PREGNANCY; WOMEN;
   HYPOTHYROIDISM; ASSOCIATION
AB Five percent of all pregnant women and 25% of pregnant women with insulin-dependent diabetes mellitus (IDDM) develop postpartum thyroiditis (PPT) during the first year after delivery. PPT has significant morbidity and can be predicted prenatally by the presence of thyroid peroxidase (TPO) antibody. Our objective was to estimate the cost-effectiveness of screening pregnant women for the TPO antibody versus the current strategy of no screening test or an alternative strategy of a thyroid-stimulating hormone (TSH) test 6 weeks postpartum. We performed cost-effectiveness analysis using a decision tree model that accounted for cases of PPT detected, medical outcomes of screening, and costs of screening and care. Hypothetical cohorts of 1000 pregnant women with uncomplicated pregnancies and 1000 pregnant women with IDDM were used to determine direct medical costs, quality-adjusted life years, and cases of PPT detected. The cost of testing 1000 pregnant women for TSH at the 6 week postpartum visit was $75,000, with an effectiveness of 995.2 quality-adjusted life years resulting in a cost-effectiveness ratio of $48,000 per quality-adjusted life year. Checking a TPO antibody was more effective (995.5 quality-adjusted life years) but also more expensive ($93,000). The incremental cost-effectiveness ratio of the TPO antibody strategy was $60,000 per quality-adjusted life year. Results were most sensitive to changes in the test characteristics, incidence of disease, and percentage of women with PPT who were symptomatic. A separate analysis for women with IDDM resulted in an incremental cost-effectiveness ratio of $13,000 per quality-adjusted life year for the TSH strategy and $32,000 per quality-adjusted life year for the TPO strategy. Screening for PPT is likely to be reasonably cost-effective and should be considered for inclusion as part of routine pregnancy care.
C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Sect Gen Med, Winston Salem, NC 27103 USA.
   Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Gen Internal Med, Boston, MA USA.
   Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA.
RP Bonds, DE (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Gen Internal Med Sect, Bowman Gray Campus,Med Ctr Blvd, Winston Salem, NC 27157 USA.
NR 38
TC 8
Z9 8
U1 0
U2 3
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 1524-6094
J9 J WOMEN HEALTH GEN-B
JI J. WOMENS HEALTH GENDER-BASED MED.
PD SEP
PY 2001
VL 10
IS 7
BP 649
EP 658
DI 10.1089/15246090152563524
PG 10
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
   Medicine; Obstetrics & Gynecology; Women's Studies
GA 474MN
UT WOS:000171111200006
PM 11571094
ER

PT J
AU Regestein, QR
   Friebely, J
   Shifren, J
   Schiff, I
AF Regestein, QR
   Friebely, J
   Shifren, J
   Schiff, I
TI Neuropsychological effects of methyltestosterone in women using
   menopausal hormone replacement
SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE
LA English
DT Article
ID POSTMENOPAUSAL WOMEN; SURGICAL MENOPAUSE; ANDROGEN; TESTOSTERONE;
   ESTROGEN; DEHYDROEPIANDROSTERONE; QUESTIONNAIRE; PROGESTIN; SYMPTOMS;
   BEHAVIOR
AB To observe the effects of androgen replacement on neuropsychological measures in menopausal women, healthy menopausal women already using replacement estrogen were studied in a randomized, double-blind, active placebo-controlled, crossover comparison between two 8-week periods of treatment with (1) 0.625 mg oral esterified estrogen (E) alone and (2) in combination with 1.25 mg oral methyltestosterone (meT). After an initial baseline session, data were gathered at the end of two treatment periods. Scores on standardized psychological tests and computerized reaction times were compared between treatments, as was an overall outcome score that combined all measures. Added meT significantly improved scores on a test of complex information processing, the Switching Attention Test, but not on other tests. Mean outcome score showed no net change and wide variation. Fourteen subjects had outcome scores > 1 SD from the mean, and 21 had no change. In the estrogen alone condition, three measures predicted favorable outcome with added meT: surgically compromised ovarian function, fewer physical symptoms, and higher score on a self-image measure of creativity. Added meT treatment may improve complex information processing. Despite wide disparities in outcome, an increased chance of overall improvement may be predicted by specific pretreatment measures.
C1 Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA.
   Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA.
RP Regestein, QR (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA.
NR 32
TC 18
Z9 18
U1 0
U2 0
PU MARY ANN LIEBERT INC PUBL
PI LARCHMONT
PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA
SN 1524-6094
J9 J WOMEN HEALTH GEN-B
JI J. WOMENS HEALTH GENDER-BASED MED.
PD SEP
PY 2001
VL 10
IS 7
BP 671
EP 676
DI 10.1089/15246090152563542
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
   Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
   Medicine; Obstetrics & Gynecology; Women's Studies
GA 474MN
UT WOS:000171111200008
PM 11571096
ER

PT J
AU DiNuzzo, AR
   Black, SA
   Lichtenstein, MJ
   Markides, KS
AF DiNuzzo, AR
   Black, SA
   Lichtenstein, MJ
   Markides, KS
TI Prevalance of functional blindness, visual impairment, and related
   functional deficits among elderly Mexican Americans
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
   SCIENCES
LA English
DT Article
ID OLDER ADULTS; POPULATION; PREVALENCE; COMMUNITY; PROJECT; VISION
AB Background. This report describes the prevalence and correlates of functional blindness and visual impairment among older Mexican Americans, using data on 2800 respondents from the Hispanic Established Populations for the Epidemiological Study of the Elderly.
   Methods. Bivariate and multivariate logistic regression analyses were used to examine the associations between corrected bilateral distant vision and sociodemographic characteristics, selected health conditions, self-reported health status. health care utilization, and functional dependence on the basis of assistance needed for basic and instrumental activities of daily living (ADLs).
   Results. Using a modified Snellen test for distance visual acuity, 5% of older Mexican Americans were found to be functionally blind. and 13.5% were found to be visually impaired. Vision loss was significantly associated with older age, lower education, hypertension, diabetes, poor self-rated health, and hospitalization during the year prior to the interview. Over 50% of functionally blind subjects required assistance with at least one basic ADL, compared with 15% of those who were visually impaired and 8% of those who were not visually impaired.
   Conclusions. The prevalence of functional blindness in this sample of elderly Mexican Americans was higher than reported for the general elderly population, yet they also have higher rates of adequate vision because of the low prevalence of visual impairment, The results suggest a need for more research on the prevalence and impact of functional blindness and Visual impairment on the health of older Mexican Americans.
C1 Univ Texas, Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77555 USA.
   Univ Texas, Med Branch, Ctr Aging, Galveston, TX 77555 USA.
   Univ Texas, Med Branch, Dept Internal Med, Galveston, TX 77555 USA.
   Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78285 USA.
   S Texas Vet Hlth Syst, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, San Antonio, TX USA.
RP Markides, KS (reprint author), Univ Texas, Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77555 USA.
FU NIA NIH HHS [AG10939]; NIDDK NIH HHS [DK51261-A]; PHS HHS [P60 A6-17231]
NR 18
TC 13
Z9 13
U1 6
U2 6
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 SEP
PY 2001
VL 56
IS 9
BP M548
EP M551
PG 4
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 468GK
UT WOS:000170749600009
PM 11524446
ER

PT J
AU Bruecher-Encke, B
   Griffin, JD
   Neel, BG
   Lorenz, U
AF Bruecher-Encke, B
   Griffin, JD
   Neel, BG
   Lorenz, U
TI Role of the tyrosine phosphatase SHP-1 in K562 cell differentiation
SO LEUKEMIA
LA English
DT Article
DE tyrosine phosphatase; differentiation; leukemia; erythroid lineage;
   myeloid lineage
ID CHRONIC MYELOGENOUS LEUKEMIA; PHOSPHOTYROSINE PHOSPHATASE;
   PHILADELPHIA-CHROMOSOME; C-ABL; KINASE-ACTIVITY; SH2 DOMAIN;
   SIGNAL-TRANSDUCTION; BCR GENE; PROTEIN; EXPRESSION
AB The erythro-megakaryoblastic leukemia cell line K562 undergoes erythroid or myeloid differentiation in response to treatment with various inducing agents. We observed that expression of the SH2-containing protein tyrosine phosphatase SHP-1 was induced upon exposure of K562 cells to differentiating agents. Under the same conditions, expression of SHP-2, a close relative of SHP-1, and the more distantly related PTP-1B remained unchanged. Induction of SHP-1 expression correlates with dephosphorylation of a specific and limited set of tyrosyl phosphoproteins, suggesting that dephosphorylation of these proteins may be important for the differentiation process. Importantly, expression of exogenous SHP-1 inhibits K562 proliferation and alters the adhesion properties of these cells, indicating a more differentiated phenotype. Moreover, SHP-1 is found in a complex with both p210 Bcr-Abl and p190 Bcr-Abl, suggesting that it may regulate Bcr-Abl or Bcr-Abl-associated phosphotyrosyl proteins. Our results indicate that induction of SHP-1 expression is important for K562 differentiation in response to various inducers and raise the possibility that functional inactivation of SHP-1 may play a role in progression to blast crisis in chronic myelogenous leukemia.
C1 Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
   Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Dept Canc Biol, Boston, MA 02215 USA.
   Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
   Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
RP Lorenz, U (reprint author), Univ Virginia, Dept Microbiol, Jordan Hall 7-46,1300 Jefferson Pk Ave, Charlottesville, VA 22908 USA.
FU NIDDK NIH HHS [P01 DK50654]
NR 47
TC 37
Z9 43
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 0887-6924
J9 LEUKEMIA
JI Leukemia
PD SEP
PY 2001
VL 15
IS 9
BP 1424
EP 1432
DI 10.1038/sj.leu.2402214
PG 9
WC Oncology; Hematology
SC Oncology; Hematology
GA 466HJ
UT WOS:000170639900013
PM 11516103
ER

PT J
AU Poorkaj, P
   Kas, A
   D'Souza, I
   Zhou, Y
   Pham, Q
   Stone, M
   Olson, MV
   Schellenberg, GD
AF Poorkaj, P
   Kas, A
   D'Souza, I
   Zhou, Y
   Pham, Q
   Stone, M
   Olson, MV
   Schellenberg, GD
TI A genomic sequence analysis of the mouse and human
   microtubule-associated protein tau
SO MAMMALIAN GENOME
LA English
DT Article
ID PROGRESSIVE SUPRANUCLEAR PALSY; MOLECULAR-WEIGHT TAU; INHERITED DEMENTIA
   FTDP-17; CENTRAL-NERVOUS-SYSTEM; LOCUS-CONTROL REGIONS; MESSENGER-RNA;
   ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; ANTISENSE OLIGONUCLEOTIDES;
   CORTICOBASAL DEGENERATION
AB Microtubule associated protein tau (MAPT) encodes the microtubule associated protein tau, the primary component of neurofibrillary tangles found in Alzheimer's disease and other neurodegenerative disorders. Mutations in the coding and intronic sequences of MAPT cause autosomal dominant frontotemporal dementia (FTDP-17). MAPT is also a candidate gene for progressive supranuclear palsy and hereditary dysphagic dementia. A human PAC (201 kb) and a mouse BAC (161 kb) containing the entire MAPT and Mtapt genes, respectively, were identified and sequenced. Comparative DNA sequence analysis revealed over 100 conserved non-repeat potential cis-acting regulatory sequences in or close to MAPT. Those islands with greater than 67% nucleotide identity range in size from 20 to greater than 1700 nucleotides. Over 90 single nucleotide, polymorphisms were identified in MAPT that are candidate susceptibility alleles for neurodegenerative disease. The 5' and 3' flanking genes for MAPT are the corticotrophin-releasing factor receptor (CRFR) gene and KIAA1267, a gene of unknown function expressed in brain.
C1 Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle Div, Seattle, WA 98108 USA.
   Univ Washington, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA.
   Univ Washington, Dept Med, Seattle, WA 98195 USA.
   Univ Washington, Dept Genet, Seattle, WA 98195 USA.
   Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
   Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
RP Schellenberg, GD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, GRECC 182B, Seattle Div, 1660 S Columbian Way, Seattle, WA 98108 USA.
FU NIA NIH HHS [R01-AG11762]; PHS HHS [P010135316]
NR 65
TC 41
Z9 46
U1 1
U2 5
PU SPRINGER-VERLAG
PI NEW YORK
PA 175 FIFTH AVE, NEW YORK, NY 10010 USA
SN 0938-8990
J9 MAMM GENOME
JI Mamm. Genome
PD SEP
PY 2001
VL 12
IS 9
BP 700
EP 712
DI 10.1007/s00335-001-2044-8
PG 13
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
   Genetics & Heredity
GA 468CG
UT WOS:000170740100005
PM 11641718
ER

PT J
AU Sullivan, EK
   Weirich, CS
   Guyon, JR
   Sif, S
   Kingston, RE
AF Sullivan, EK
   Weirich, CS
   Guyon, JR
   Sif, S
   Kingston, RE
TI Transcriptional activation domains of human heat shock factor 1 recruit
   human SWI/SNF
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID RNA-POLYMERASE-II; CHROMATIN REMODELING COMPLEX; TATA-BINDING PROTEIN;
   NUCLEOSOMAL TEMPLATES; FACILITATED BINDING; GENE-TRANSCRIPTION; NUCLEAR
   RECEPTORS; REGULATORS; ELONGATION; ENHANCEMENT
AB Chromatin remodeling complexes such as SWI/SNF use the energy of ATP hydrolysis to remodel nucleosomal DNA and increase transcription of nucleosomal templates. Human heat shock factor one (hHSF1) is a tightly regulated activator that stimulates transcriptional initiation and elongation using different portions of its activation domains. Here we demonstrate that hHSF1 associates with BRG1, the ATPase subunit of human SWI/SNF (hSWI/SNF) at endogenous protein concentrations. We also show that hHSF1 activation domains recruit hSWI/SNF to a chromatin template in a purified system. Mutation of hHSF1 residues responsible for activation of transcriptional elongation has the most severe effect on recruitment of SWI/SNF and association of hHSF1 with BRG1, suggesting that recruitment of chromatin remodeling activity might play a role in stimulation of elongation.
C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.
RP Sullivan, EK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA.
NR 58
TC 68
Z9 70
U1 0
U2 2
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 SEP
PY 2001
VL 21
IS 17
BP 5826
EP 5837
DI 10.1128/MCB.21.17.5826-5837.2001
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 461DP
UT WOS:000170349900013
PM 11486022
ER

PT J
AU Dang, JJ
   Inukai, T
   Kurosawa, H
   Goi, K
   Inaba, T
   Lenny, NT
   Downing, JR
   Stifani, S
   Look, T
AF Dang, JJ
   Inukai, T
   Kurosawa, H
   Goi, K
   Inaba, T
   Lenny, NT
   Downing, JR
   Stifani, S
   Look, T
TI The E2A-HLF oncoprotein activates Groucho-related genes and suppresses
   Runx1
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID CHIMERIC TRANSCRIPTION FACTOR; ACUTE MYELOID-LEUKEMIA;
   DROSOPHILA-ENHANCER; CHROMOSOMAL TRANSLOCATIONS; COREPRESSOR GROUCHO;
   MESSENGER-RNA; SPLIT COMPLEX; TARGET GENES; WD-REPEAT; PROTEINS
AB The E2A-HLF fusion gene, formed by the t(17;19)(q22;p13) chromosomal translocation in leukemic pro-B cells, encodes a chimeric transcription factor consisting of the transactivation domain of E2A linked to the bZIP DNA-binding and protein dimerization domain of hepatic leukemia factor (HLF). This oncoprotein blocks apoptosis induced by growth factor deprivation or irradiation, but the mechanism for this effect remains unclear. We therefore performed representational difference analysis (RDA) to identify downstream genetic targets of E2A-HLF, using a murine FL5.12 pro-B cell line that had been stably transfected with E2A-HLF cDNA under the control of a zinc-regulated metallothionein promoter. Two RDA clones, designated RDA1 and RDA3, were differentially upregulated in E2A-HLF-positive cells after zinc induction. The corresponding cDNAs encoded two WD40 repeat-containing proteins, Grg2 and Grg6. Both are related to the Drosophila protein Groucho, a transcriptional corepressor that lacks DNA-binding activity on its own but can act in concert with other proteins to regulate embryologic development of the fly. Expression of both Grg2 and Grg6 was upregulated 10- to 50-fold by E2A-HLF. Immunoblot analysis detected increased amounts of two additional Groucho-related proteins, Grg1 and Grg4, in cells expressing E2A-HLF. A mutant E2A-HLF protein with a disabled DNA-binding region also mediated pro-B cell survival and activated Groucho-related genes. Among the transcription factors known to interact with Groucho-related protein, only RUNX1 was appreciably downregulated by E2A-HLF. Our results identify a highly conserved family of transcriptional corepressors that are activated by E2A-HLF, and they suggest that downregulation of RUNX1 may contribute to E2A-HLF-mediated leukemogenesis.
C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   St Jude Childrens Res Hosp, Dept Expt Oncol, Memphis, TN 38105 USA.
   St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
   Jichi Med Sch, Dept Mol Biol & Hematol, Minami Kawachi, Tochigi 32904, Japan.
   McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2B4, Canada.
RP Look, T (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer 630, Boston, MA 02115 USA.
EM thomas_look@dfci.harvard.edu
FU NCI NIH HHS [CA21765, CA59571, P30 CA021765, R01 CA059571]
NR 54
TC 32
Z9 34
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 SEP
PY 2001
VL 21
IS 17
BP 5935
EP 5945
DI 10.1128/MCB.21.17.5935-5945.2001
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 461DP
UT WOS:000170349900023
PM 11486032
ER

PT J
AU Lu, XD
   Magrane, G
   Yin, CY
   Louis, DN
   Gray, J
   Van Dyke, T
AF Lu, XD
   Magrane, G
   Yin, CY
   Louis, DN
   Gray, J
   Van Dyke, T
TI Selective inactivation of p53 facilitates mouse epithelial tumor
   progression without chromosomal instability
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID WILD-TYPE P53; CELL-CYCLE CONTROL; COMPARATIVE GENOMIC HYBRIDIZATION;
   TRANSGENIC MICE; P53-DEFICIENT MICE; GENE AMPLIFICATION; SUPPRESSOR
   GENE; POINT MUTATIONS; APOPTOSIS; CHECKPOINT
AB We examined the selective pressure for, and the impact of, p53 inactivation during epithelial tumor evolution in a transgenic brain tumor model. In TgT(121) Mice, cell-specific inactivation of the pRb pathway in brain choroid plexus epithelium initiates tumorigenesis and induces p53-dependent apoptosis. We previously showed that p53 deficiency accelerates tumor growth due to diminished apoptosis. Here we show that in a p53(+/-) background, slow-growing dysplastic tissue undergoes clonal progression to solid angiogenic tumors in all animals. p53 is inactivated in all progressed tumors, with loss of the wild-type allele occurring in 90% of tumors. Moreover, similar progression occurs in 38% of TgT(121)p53(+/+) mice, also with loss of at least one p53 allele and inactivation of p53. Thus, the selective pressure for p53 inactivation, likely based on its apoptotic function, is high. Yet, in all cases, p53 inactivation correlates with progression beyond apoptosis reduction, from dysplasia to solid vascularized tumors. Hence, p53 suppresses tumor progression in this tissue by multiple mechanisms. Previous studies of fibroblasts and hematopoietic cells show that p53 deficiency can be associated with chromosomal instability, a mechanism that may drive tumor progression. To determine whether genomic gains or losses are present in tumors that progress in the absence of p53, we performed comparative genomic hybridization analysis. Surprisingly, the only detectable chromosomal imbalance was partial or complete loss of chromosome 11, which harbors the p53 gene and is thus the selected event. Flow cytometry confirmed that the majority of tumor cells were diploid. These studies indicate that loss of p53 function is frequent under natural selective pressures and furthermore that p53 loss can facilitate epithelial tumor progression by a mechanism in addition to apoptosis reduction and distinct from chromosomal instability.
C1 Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
   Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
   Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab, Charlestown, MA 02129 USA.
RP Van Dyke, T (reprint author), Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
FU NCI NIH HHS [R01 CA046283, 1R01 CA46283, 5U01 CA84314, U01 CA084314]
NR 75
TC 46
Z9 46
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 SEP
PY 2001
VL 21
IS 17
BP 6017
EP 6030
DI 10.1128/MCB.21.17.6017-6030.2001
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 461DP
UT WOS:000170349900030
PM 11486039
ER

PT J
AU Ito, Y
   Pandey, P
   Mishra, N
   Kumar, S
   Narula, N
   Kharbanda, S
   Saxena, S
   Kufe, D
AF Ito, Y
   Pandey, P
   Mishra, N
   Kumar, S
   Narula, N
   Kharbanda, S
   Saxena, S
   Kufe, D
TI Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic
   reticulum stress-induced Apoptosis
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID N-LINKED GLYCOSYLATION; GLUCOSE-REGULATED PROTEINS; DNA-DAMAGE;
   CELLULAR-RESPONSE; POLY(ADP-RIBOSE) POLYMERASE; APOPTOTIC RESPONSE;
   CYTOCHROME-C; ACTIVATION; CELLS; INDUCTION
AB The ubiquitously expressed c-Abl tyrosine kinase localizes to the nucleus and cytoplasm. Using confocal microscopy, we demonstrated that c-Abl colocalizes with the endoplasmic reticulum (ER)-associated protein grp78. Expression of c-Abl in the ER was confirmed by immunoelectron microscopy. Subcellular fractionation studies further indicate that over 20% of cellular c-Abl is detectable in the ER. The results also demonstrate that induction of ER stress with calcium ionophore A23187, brefeldin A, or tunicamycin is associated with translocation of ER-associated c-Abl to mitochondria. In concert with targeting of c-Abl to mitochondria, cytochrome c is released in the response to ER stress by a c-Abl-dependent mechanism, and ER stress-induced apoptosis is attenuated in c-Abl-deficient cells. These findings indicate that c-Abl is involved in signaling from the ER to mitochondria and thereby the apoptotic response to ER stress.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
   Lovelace Resp Res Inst, Albuquerque, NM 87115 USA.
   Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM Donald_Kufe@dfci.harvard.edu
FU NCI NIH HHS [CA42803, R01 CA042802]
NR 42
TC 94
Z9 103
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 SEP
PY 2001
VL 21
IS 18
BP 6233
EP 6242
DI 10.1128/MCB.21.18.6233-6242.2001
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 466AN
UT WOS:000170622300015
PM 11509666
ER

PT J
AU Francis, NJ
   Saurin, AJ
   Shao, ZH
   Kingston, RE
AF Francis, NJ
   Saurin, AJ
   Shao, ZH
   Kingston, RE
TI Reconstitution of a functional core polycomb repressive complex
SO MOLECULAR CELL
LA English
DT Article
ID CHROMATIN REMODELING COMPLEX; CHROMOSOME-BINDING-SITES; YEAST SWI/SNF
   COMPLEX; GROUP PROTEINS; GROUP GENES; TRANSCRIPTIONAL REPRESSION;
   DROSOPHILA-MELANOGASTER; SWI-SNF; TRITHORAX; ENCODES
AB The opposing actions of polycomb (PcG) and trithorax group (trxG) gene products maintain essential gene expression patterns during Drosophila development. PcG proteins are thought to establish repressive chromatin structures, but the mechanisms by which this occurs are not known. Polycomb repressive complex 1 (PRC1) contains several PcG proteins and inhibits chromatin remodeling by trxG-related SWI/SNF complexes. We have defined a functional core of PRC1 by reconstituting a stable complex using four recombinant PcG proteins. One subunit, PSC, can also inhibit chromatin remodeling on its own. These PcG proteins create a chromatin structure that has normal nucleosome organization and is accessible to nucleases but excludes hSWI/SNF.
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 46
TC 235
Z9 245
U1 1
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD SEP
PY 2001
VL 8
IS 3
BP 545
EP 556
DI 10.1016/S1097-2765(01)00316-1
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 476WJ
UT WOS:000171251500010
PM 11583617
ER

PT J
AU Cheng, EHYA
   Wei, MC
   Weiler, S
   Flavell, RA
   Mak, TW
   Lindsten, T
   Korsmeyer, SJ
AF Cheng, EHYA
   Wei, MC
   Weiler, S
   Flavell, RA
   Mak, TW
   Lindsten, T
   Korsmeyer, SJ
TI BCL-2, BCL-X-L sequester BH3 domain-only molecules preventing BAX- and
   BAK-mediated mitochondrial apoptosis
SO MOLECULAR CELL
LA English
DT Article
ID PROGRAMMED CELL-DEATH; CYTOCHROME-C; PROTEIN; FAMILY; ACTIVATION;
   BCL-X(L); MEMBRANE; ELEGANS; RELEASE; DIMERIZATION
AB Critical issues in apoptosis include the importance of caspases versus organelle dysfunction, dominance of anti- versus proapoptotic BCL-2 members, and whether commitment occurs upstream or downstream of mitochondria. Here, we show cells deficient for the downstream effectors Apaf-1, Caspase-9, or Caspase-3 display only transient protection from "BH3 domain-only" molecules and die a caspase-independent death by mitochondrial dysfunction. Cells with an upstream defect, lacking "multidomain" BAX, BAK demonstrate long-term resistance to all BH3 domain-only members, including BAD, BIM, and NOXA. Comparison of wild-type versus mutant BCL-2, BCL-X-L indicates these antiapoptotics sequester BH3 domain-only molecules in stable mitochondrial complexes, preventing the activation of BAX, BAK. Thus, in mammals, BH3 domain-only molecules activate multidomain proapoptotic members to trigger a mitochondrial pathway, which both releases cytochrome c to activate caspases and initiates caspase-independent mitochondrial dysfunction.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA.
   Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06520 USA.
   Ontario Canc Inst, Div Cellular & Mol Biol, Amgen Inst, Toronto, ON M5G 2M9, Canada.
   Univ Penn, Dept Pathol & Lab Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA.
RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA.
FU NCI NIH HHS [R01CA50239]
NR 35
TC 1098
Z9 1152
U1 9
U2 63
PU CELL PRESS
PI CAMBRIDGE
PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA
SN 1097-2765
J9 MOL CELL
JI Mol. Cell
PD SEP
PY 2001
VL 8
IS 3
BP 705
EP 711
DI 10.1016/S1097-2765(01)00320-3
PG 7
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 476WJ
UT WOS:000171251500024
PM 11583631
ER

PT J
AU Fleming, JC
   Steinkamp, MP
   Kawatsuji, R
   Tartaglini, E
   Pinkus, JL
   Pinkus, GS
   Fleming, MD
   Neufeld, EJ
AF Fleming, JC
   Steinkamp, MP
   Kawatsuji, R
   Tartaglini, E
   Pinkus, JL
   Pinkus, GS
   Fleming, MD
   Neufeld, EJ
TI Characterization of a murine high-affinity thiamine transporter, Slc19a2
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
ID RESPONSIVE MEGALOBLASTIC-ANEMIA; GENE; MUTATIONS; DEAFNESS
AB Thiamine-responsive megaloblastic anemia with deafness and diabetes (TRMA) is a rare autosomal recessive disorder of thiamine transport. Previous studies have demonstrated that the disease is caused by mutations in the SLC19A2 gene encoding a high-affinity thiamine transporter. We hypothesize that thiamine transport, mediated by SLC19A2, plays a role in the development and or maintenance of several organ systems, in particular the erythropoietic, auditory, and glucose homeostasis systems. To investigate the transporter further, we cloned the murine Slc19a2 locus and characterized the resulting protein. Murine Slc19a2 is a 498 amino acid protein, with 12 predicted transmembrane domains. The gene spans similar to 13kb with 6 exons, structurally identical to that of the human homolog. We localized the Slc19a2 gene to mouse chromosome 1, a region syntenic to human chromosome 1q23 that contains the TRMA locus. Transient expression of Slc19a2 in HEK293T cells resulted in specific uptake of [H-3] thiamine, confirming a thiamine transporter function. Western blot analysis of mouse tissues reveals a wide distribution of Slc19a2 protein. Immunohistochemistry studies indicate that Slc19a2 is expressed on the cell surface and intracellularly, and is specifically localized to a subpopulation of cells in cochlea, small intestine, and pancreas. (C) 2001 Academic Press.
C1 Childrens Hosp, Div Hematol, Dana Farber Canc Inst, Boston, MA 02115 USA.
   Harvard Univ, Sch Med, Boston, MA 02115 USA.
   Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
   Childrens Hosp, Dept Pathol, Boston, MA 02115 USA.
RP Neufeld, EJ (reprint author), Childrens Hosp, Div Hematol, Dana Farber Canc Inst, 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 [K24 HL04184]
NR 14
TC 24
Z9 26
U1 0
U2 2
PU ACADEMIC PRESS INC
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD SEP-OCT
PY 2001
VL 74
IS 1-2
BP 273
EP 280
DI 10.1006/mgme.2001.3241
PG 8
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
   Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
   Medicine
GA 480NW
UT WOS:000171468700025
PM 11592824
ER

PT J
AU Gibson, ME
   Han, BH
   Choi, JJ
   Knudson, CM
   Korsmeyer, SJ
   Parsadanian, M
   Holtzman, DM
AF Gibson, ME
   Han, BH
   Choi, JJ
   Knudson, CM
   Korsmeyer, SJ
   Parsadanian, M
   Holtzman, DM
TI BAX contributes to apoptotic-like death following neonatal
   hypoxia-ischemia: Evidence for distinct apoptosis pathways
SO MOLECULAR MEDICINE
LA English
DT Article
ID CYTOCHROME-C RELEASE; TRANSIENT FOREBRAIN ISCHEMIA; IN-SITU
   IMMUNODETECTION; PERINATAL BRAIN INJURY; DEVELOPING RAT-BRAIN;
   CELL-DEATH; CEREBRAL-ISCHEMIA; NEURONAL DEATH; NERVOUS-SYSTEM; CASPASE-3
   ACTIVATION
AB Background: Hypoxic-ischemic (H-I) injury to the neonatal brain has been shown to result in rapid cell death with features of acute excitotoxicity/necrosis as well as prominent delayed cell death with features of apoptosis such as marked caspase-3 activation. BAX, a pro-apoptotic molecule, has been shown to be required for apoptotic neuronal cell death during normal development but the contribution of endogenous BAX in cell death pathways following H-I injury to the developing or adult brain has not been studied.
   Materials and Methods: Bax +/+, +/-, and -/- mice at post-natal day 7 were subjected to unilateral carotid ligation followed by exposure to 45 minutes of 8% oxygen. At different timepoints following H-I, brain tissue was studied by conventional histology, immunohistochemistry, immunofluorescence, Western blotting, and enzymatic assay to determine the extent and type of cell injury as well as the amount of caspase activation.
   Results: We found that bax -/- mice had significantly less (38%) hippocampal tissue loss than mice expressing bax. Some of the remaining cell death in bax -/- mice, however, still had features of apoptosis including evidence of nuclear shrinkage and caspase-3 activation. Though bax -/- mice had significantly decreased caspase-3 activation as compared to bax expressing mice following H-I, the density of cells with activated caspase-8 in the CA3 region of the hippocampus did not differ between bax +/- and bax -/- mice.
   Conclusions: These findings demonstrate that endogenous BAX plays a role in regulating cell death in the central nervous system (CNS) following neonatal H-I. a model of cerebral palsy. in addition, while BAX appears to modulate the caspase-3 activation following neonatal H-I, caspase-8 which is linked to death receptor activation, may contribute to apoptotic-like neuronal death in a BAX-independent manner.
C1 Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
   Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA.
   Washington Univ, Sch Med, Ctr Study Nervous Syst Injury, St Louis, MO 63110 USA.
   Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA.
   Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med, Boston, MA 02115 USA.
RP Holtzman, DM (reprint author), Washington Univ, Sch Med, Dept Neurol, 660 S Euclid Ave,Box 8111, St Louis, MO 63110 USA.
FU NINDS NIH HHS [NS35902]
NR 78
TC 82
Z9 91
U1 0
U2 1
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
   21218-4319 USA
SN 1076-1551
J9 MOL MED
JI Mol. Med.
PD SEP
PY 2001
VL 7
IS 9
BP 644
EP 655
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 481PQ
UT WOS:000171528900008
PM 11778654
ER

PT J
AU Yorgey, P
   Rahme, LG
   Tan, MW
   Ausubel, FM
AF Yorgey, P
   Rahme, LG
   Tan, MW
   Ausubel, FM
TI The roles of mucD and alginate in the virulence of Pseudomonas
   aeruginosa in plants, nematodes and mice
SO MOLECULAR MICROBIOLOGY
LA English
DT Article
ID ESCHERICHIA-COLI SURVIVAL; STRESS-RESPONSE PROTEIN; SIGMA-FACTOR;
   CYSTIC-FIBROSIS; CAENORHABDITIS-ELEGANS; BRUCELLA-ABORTUS;
   HIGH-TEMPERATURE; SERINE-PROTEASE; EXTRACYTOPLASMIC STRESS; MACROPHAGE
   PHAGOCYTOSIS
AB We are exploiting the broad host range of the human opportunistic pathogen Pseudomonas aeruginosa strain PA14 to elucidate the molecular basis of bacterial virulence in plants, nematodes, insects and mice. In this report, we characterize the role that two PA14 gene products, MucD and AlgD, play in virulence. MucD is orthologous to the Escherichia coli periplasmic protease and chaperone DegP. DegP homologues are known virulence factors that play a protective role in stress responses in various species. AlgD is an enzyme involved in the biosynthesis of the exopolysaccharide alginate, which is hyperinduced in mucD mutants. A PA14 mucD mutant was significantly impaired in its ability to cause disease in Arabidopsis thaliana and mice and to kill the nematode Caenorhabditis elegans. Moreover, MucD was found to be required for the production of an extracellular toxin involved in C. elegans killing. In contrast, a PA14 algD mutant was not impaired in virulence in plants, nematodes or mice. A mucDalgD double mutant had the same phenotype as the mucD single mutant in the plant and nematode pathogenesis models. However, the mucDalgD double mutant was synergistically reduced in virulence in mice, suggesting that alginate can partially compensate for the loss of MucD function in mouse pathogenesis.
C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
   Shriners Burn Inst, Boston, MA 02114 USA.
   Harvard Univ, Soc Fellows, Cambridge, MA 02138 USA.
RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA.
FU NIGMS NIH HHS [T32 GM07035]
NR 70
TC 63
Z9 67
U1 1
U2 16
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 SEP
PY 2001
VL 41
IS 5
BP 1063
EP 1076
DI 10.1046/j.1365-2958.2001.02580.x
PG 14
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA 477YQ
UT WOS:000171314500010
PM 11555287
ER

PT J
AU Akbarian, S
   Bates, B
   Liu, RJ
   Skirboll, SL
   Pejchal, T
   Coppola, V
   Sun, LD
   Fan, G
   Kucera, J
   Wilson, MA
   Tessarollo, L
   Kosofsky, BE
   Taylor, JR
   Bothwell, M
   Nestler, EJ
   Aghajanian, GK
   Jaenisch, R
AF Akbarian, S
   Bates, B
   Liu, RJ
   Skirboll, SL
   Pejchal, T
   Coppola, V
   Sun, LD
   Fan, G
   Kucera, J
   Wilson, MA
   Tessarollo, L
   Kosofsky, BE
   Taylor, JR
   Bothwell, M
   Nestler, EJ
   Aghajanian, GK
   Jaenisch, R
TI Neurotrophin-3 modulates noradrenergic neuron function and opiate
   withdrawal
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE locus coeruleus; morphine; addiction; norepinephrine; cre recombinase;
   pons; medulla
ID MESSENGER-RNA EXPRESSION; LOCUS-COERULEUS; RAT-BRAIN; ANTEROGRADE
   TRANSPORT; TRANSGENIC MICE; NERVOUS-SYSTEM; PROTEIN-KINASE; NT-3;
   CERULEUS; TRKC
AB Somatic symptoms and aversion of opiate withdrawal, regulated by noradrenergic signaling, were attenuated in mice with a CNS-wide conditional ablation of neurotrophin-3. This occurred in conjunction with altered cAMP-mediated excitation and reduced upregulation of tyrosine hydroxylase in A6 (locus coeruleus) without loss of neurons. Transgene-derived NT-3 expressed by noradrenergic neurons of conditional mutants restored opiate withdrawal symptoms. Endogenous NT-3 expression, strikingly absent in noradrenergic neurons of postnatal and adult brain, is present in afferent sources of the dorsal medulla and is upregulated after chronic morphine exposure in noradrenergic projection areas of the ventral forebrain. NT-3 expressed by noncatecholaminergic neurons may modulate opiate withdrawal and noradrenergic signalling.
C1 Whitehead Inst, Cambridge, MA 02142 USA.
   Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
   Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
   Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
   Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA.
   NCI, Frederick, MD 21701 USA.
   MIT, Dept Biol, Cambridge, MA USA.
   Boston Univ, Dept Neurol, Boston, MA 02215 USA.
RP Jaenisch, R (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA.
RI Coppola, Vincenzo/E-2917-2011; 
OI Coppola, Vincenzo/0000-0001-6163-1779; Fan, Guoping/0000-0001-5235-6410
FU NCI NIH HHS [5-R35-CA44339]; NIDA NIH HHS [1-K08-DA00479]
NR 50
TC 20
Z9 22
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI BASINGSTOKE
PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND
SN 1359-4184
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD SEP
PY 2001
VL 6
IS 5
BP 593
EP 604
DI 10.1038/sj.mp.4000897
PG 12
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA 461CG
UT WOS:000170346900014
PM 11526474
ER

PT J
AU Pellman, D
   Christman, MF
AF Pellman, D
   Christman, MF
TI Separase anxiety: dissolving the sister bond and more
SO NATURE CELL BIOLOGY
LA English
DT Article
ID CHROMATID SEPARATION; CUT2 PROTEOLYSIS; BUDDING YEAST; FISSION YEAST;
   MITOTIC EXIT; ANAPHASE; SPINDLE; ESP1; DUPLICATION; CHROMOSOME
AB Separase is a protease that cleaves the bonds between sister chromatids during cell division. Until now, separase was thought to be a somewhat repressed protease, cleaving only a few substrates in a very controlled fashion. New findings in this issue raise the possibility that separase has some of the atavistic impulses that characterize caspases, its more destructive relatives.
C1 Dana Farber Canc Inst, Boston, MA 02115 USA.
   Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA.
RP Pellman, D (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
NR 21
TC 5
Z9 6
U1 0
U2 1
PU MACMILLAN PUBLISHERS LTD
PI LONDON
PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD SEP
PY 2001
VL 3
IS 9
BP E207
EP E209
DI 10.1038/ncb0901-e207
PG 3
WC Cell Biology
SC Cell Biology
GA 472JC
UT WOS:000170979600005
PM 11533673
ER

PT J
AU Benoist, C
   Mathis, D
AF Benoist, C
   Mathis, D
TI Autoimmunity provoked by infection: how good is the case for T cell
   epitope mimicry?
SO NATURE IMMUNOLOGY
LA English
DT Review
ID SURFACE PROTEIN-A; HERPES STROMAL KERATITIS; RESISTANT LYME ARTHRITIS;
   SIMPLEX VIRUS TYPE-1; BORRELIA-BURGDORFERI; MOLECULAR MIMICRY; DISEASE;
   IDENTIFICATION; ASSOCIATION; REACTIVITY
AB Autoimmune diseases remain one of the mysteries that perplex immunologists. What makes the immune system, which has evolved to protect an organism from foreign invaders, turn on the organism itself? A popular answer to this question involves the lymphoid network's primordial function: autoimmunity is a by-product of the immune response to microbial infection. For decades there have been tantalizing associations between infectious agents and autoimmunity: beta -hemolytic streptococci and rheumatic fever; B3 Coxsackieviruses and myocarditis; Trypanosoma cruzi and Chagas' disease; diverse viruses and multiple sclerosis; Borrelia burgdorfii and Lyme arthritis; and B4 Coxsackievirus, cytomegalovirus or rubella and type I diabetes, to name the most frequently cited examples'. In addition, animal models have provided direct evidence that infection with a particular microbe can incite a particular autoimmune disease(2). Nonetheless, many of the associations appear less than convincing and, even for those that seem to be on solid footing' there is no real understanding of the underlying mechanism(s).
C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02115 USA.
RP Mathis, D (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02115 USA.
NR 41
TC 272
Z9 286
U1 1
U2 22
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 SEP
PY 2001
VL 2
IS 9
BP 797
EP 801
DI 10.1038/ni0901-797
PG 5
WC Immunology
SC Immunology
GA 468WM
UT WOS:000170781200014
PM 11526389
ER

PT J
AU Gounari, F
   Aifantis, I
   Khazaie, K
   Hoeflinger, S
   Harada, N
   Taketo, MM
   von Boehmer, H
AF Gounari, F
   Aifantis, I
   Khazaie, K
   Hoeflinger, S
   Harada, N
   Taketo, MM
   von Boehmer, H
TI Somatic activation of beta-catenin bypasses pre-TCR signaling and TCR
   selection in thymocyte development
SO NATURE IMMUNOLOGY
LA English
DT Article
ID T-CELL-RECEPTOR; LYMPHOCYTE DEVELOPMENT; GAMMA-CHAIN; ALPHA GENE; BCL-2;
   MICE; DIFFERENTIATION; PROGENITORS; EXPRESSION; DEFICIENT
AB Mutation or ablation of T cell factor I and lymphocyte enhancer factor I indicated involvement of the Wnt pathway in thymocyte development. The central effector of the Wnt pathway is beta -catenin, which undergoes stabilization upon binding of Wnt ligands to frizzled receptors. We report here that conditional stabilization of beta -catenin in immature thymocytes resulted in the generation of single positive T cells that lacked the alpha beta TCR and developed in the absence of pre-TCR signaling and TCR selection. Although active beta -catenin induced differentiation in the absence of TCRs, its action was associated with reduced proliferation and survival when compared to developmental changes induced by the pre-TCR or the alpha beta TCR.
C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA.
   Merck, Banyu Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan.
   Kyoto Univ, Grad Sch Med, Dept Pharmacol, Sakyo Ku, Kyoto 6068501, Japan.
RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, 44 Binney St, Boston, MA 02115 USA.
FU NIAID NIH HHS [R01AI47281, R01AI45846]
NR 34
TC 143
Z9 146
U1 0
U2 3
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 SEP
PY 2001
VL 2
IS 9
BP 863
EP 869
DI 10.1038/ni0901-863
PG 7
WC Immunology
SC Immunology
GA 468WM
UT WOS:000170781200027
PM 11526403
ER

PT J
AU Jain, RK
AF Jain, RK
TI Normalizing tumor vasculature with anti-angiogenic therapy: A new
   paradigm for combination therapy
SO NATURE MEDICINE
LA English
DT Editorial Material
ID ENDOTHELIAL GROWTH-FACTOR; BLOOD-VESSELS; SOLID TUMORS; CANCER;
   CHEMOTHERAPY; ABLATION; DELIVERY
C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA.
   Harvard Univ, Sch Med, Boston, MA USA.
RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA 02114 USA.
NR 28
TC 1127
Z9 1181
U1 9
U2 60
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 SEP
PY 2001
VL 7
IS 9
BP 987
EP 989
DI 10.1038/nm0901-987
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
   Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
   Medicine
GA 470CR
UT WOS:000170853300012
PM 11533692
ER

PT J
AU Masland, RH
AF Masland, RH
TI The fundamental plan of the retina
SO NATURE NEUROSCIENCE
LA English
DT Review
ID LATERAL GENICULATE-NUCLEUS; GANGLION-CELL TYPE; MACAQUE MONKEY RETINA;
   STARBURST AMACRINE CELLS; ACCESSORY OPTIC-SYSTEM; HUMAN COLOR-VISION;
   INNER PLEXIFORM LAYER; CONE BIPOLAR CELLS; RABBIT RETINA; CAT RETINA
AB The retina, like many other central nervous system structures, contains a huge diversity of neuronal types. Mammalian retinas contain approximately 55 distinct cell types, each with a different function. The census of cell types is nearing completion, as the development of quantitative methods makes it possible to be reasonably confident that few additional types exist. Although much remains to be learned, the fundamental structural principles are now becoming clear. They give a bottom-up view of the strategies used in the retina's processing of visual information and suggest new questions for physiological experiments and modeling.
C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA.
RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Wellman 429, Boston, MA 02114 USA.
EM masland@helix.mgh.harvard.edu
NR 125
TC 564
Z9 580
U1 11
U2 91
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD SEP
PY 2001
VL 4
IS 9
BP 877
EP 886
DI 10.1038/nn0901-877
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 467JL
UT WOS:000170698600013
PM 11528418
ER

PT J
AU Passafaro, M
   Piech, V
   Sheng, M
AF Passafaro, M
   Piech, V
   Sheng, M
TI Subunit-specific temporal and spatial patterns of AMPA receptor
   exocytosis in hippocampal neurons
SO NATURE NEUROSCIENCE
LA English
DT Article
ID LONG-TERM DEPRESSION; DOMAIN-CONTAINING PROTEINS; GLUTAMATE RECEPTORS;
   SYNAPTIC PLASTICITY; BREFELDIN-A; MEMBRANE; SYNAPSES; GLUR2; LTP;
   REDISTRIBUTION
AB Using a thrombin cleavage assay in cultured hippocampal neurons, we studied the kinetics, regulation and site of AMPA receptor surface delivery. Surface insertion of the GluR1 subunit occurs slowly in basal conditions and is stimulated by NMDA receptor activation and insulin, whereas GluR2 exocytosis is constitutively rapid. Although both subunits ultimately concentrate in synapses, GluR1 and GluR2 show different spatial patterns of surface accumulation, consistent with GluR1 being inserted initially at extrasynaptic sites and GluR2 being inserted more directly at synapses. The spatiotemporal pattern of surface accumulation is determined by the cytoplasmic tails of GluR subunits, and in heteromeric receptors, GluR1 acts dominantly over GluR2. We propose that GluR1 controls the exocytosis and GluR2/3, the recycling and endocytosis of AMPA receptors.
C1 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.
RP Sheng, M (reprint author), MIT, Ctr Learning & Memory, E18-215,77 Massachusetts Ave, Cambridge, MA 02139 USA.
FU NINDS NIH HHS [NS 35050]
NR 43
TC 422
Z9 438
U1 1
U2 8
PU NATURE AMERICA INC
PI NEW YORK
PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA
SN 1097-6256
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD SEP
PY 2001
VL 4
IS 9
BP 917
EP 926
DI 10.1038/nn0901-917
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 467JL
UT WOS:000170698600018
PM 11528423
ER

PT J
AU Matsuda, C
   Hayashi, YK
   Ogawa, M
   Aoki, M
   Murayama, K
   Nishino, I
   Nonaka, I
   Arahata, K
   Brown, RH
AF Matsuda, C
   Hayashi, YK
   Ogawa, M
   Aoki, M
   Murayama, K
   Nishino, I
   Nonaka, I
   Arahata, K
   Brown, RH
TI The sarcolemmal proteins dysferlin and caveolin-3 interact in skeletal
   muscle
SO NEUROMUSCULAR DISORDERS
LA English
DT Meeting Abstract
DE dysferlin; caveolin-3; LGMD1C
C1 AIST, Res Inst Neurosci, Mol Neurobiol Grp, Osaka, Japan.
   Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Kodaira, Tokyo, Japan.
   Tohoku Univ, Sch Med, Dept Neurol, Sendai, Miyagi 980, Japan.
   Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Ultrastruct Res, Kodaira, Tokyo, Japan.
   Massachusetts Gen Hosp East, Day Neuromuscular Res Lab, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD SEP
PY 2001
VL 11
IS 6-7
BP 626
EP 626
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 469NQ
UT WOS:000170822100053
ER

PT J
AU Blevins, JE
   Eakin, TJ
   Murphy, JA
   Schwartz, MW
   Baskin, DG
AF Blevins, JE
   Eakin, TJ
   Murphy, JA
   Schwartz, MW
   Baskin, DG
TI Oxytocin innervation of caudal brainstem areas activated by
   cholecystokinin
SO OBESITY RESEARCH
LA English
DT Meeting Abstract
C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA.
   Univ Washington, Seattle, WA 98195 USA.
RI Schwartz, Michael/H-9950-2012
NR 0
TC 1
Z9 1
U1 0
U2 1
PU NORTH AMER ASSOC STUDY OBESITY
PI ROCHESTER
PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW,
   ROCHESTER, MN 55905 USA
SN 1071-7323
J9 OBES RES
JI Obes. Res.
PD SEP
PY 2001
VL 9
SU 3
BP 56S
EP 56S
PG 1
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 473YF
UT WOS:000171076300014
ER

PT J
AU Cornier, MA
   Donahoo, W
   Black, J
   Stephens, E
   Hill, J
   Eckel, R
   Draznin, B
AF Cornier, MA
   Donahoo, W
   Black, J
   Stephens, E
   Hill, J
   Eckel, R
   Draznin, B
TI Insulin sensitivity determines the effectiveness of macronutrient
   composition of the diet on weight loss
SO OBESITY RESEARCH
LA English
DT Meeting Abstract
C1 Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA.
   Denver VA Med Ctr, Denver, CO USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NORTH AMER ASSOC STUDY OBESITY
PI ROCHESTER
PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW,
   ROCHESTER, MN 55905 USA
SN 1071-7323
J9 OBES RES
JI Obes. Res.
PD SEP
PY 2001
VL 9
SU 3
BP 79S
EP 79S
PG 1
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 473YF
UT WOS:000171076300108
ER

PT J
AU Stavrou, P
   Baltatzis, S
   Letko, E
   Samson, CM
   Christen, W
   Foster, CS
AF Stavrou, P
   Baltatzis, S
   Letko, E
   Samson, CM
   Christen, W
   Foster, CS
TI Pars plana vitrectomy in patients with intermediate uveitis
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Article
DE pars plana vitrectomy; intermediate uveitis
ID PLANITIS; COMPLICATIONS; MANAGEMENT; FEATURES
AB Objective: To describe the effect of pars plana vitrectomy in patients with intermediate uveitis. Methods: Retrospective analysis of the clinical course and visual outcome following pars plana vitrectomy in patients with intermediate uveitis. Results: Thirty-two patients (43 eyes) were included in the study. Pars plana vitrectomy was combined with cataract surgery in 22 of 43 eyes. The intermediate uveitis was associated with sarcoidosis in 16 eyes and multiple sclerosis in five eyes, and was idiopathic in 22 eyes. The mean (+/- SD) follow-up was 45.6 (+/- 38) months (range: 6-146 months). In 19 of 43 eyes (44.1%), there was improvement in the course of uveitis, allowing the discontinuation of immunosuppressive treatment in seven patients. Cystoid macular edema resolved in 12 of 37 eyes (32.4%). Forty of 43 eyes achieved a better or retained their initial visual acuity. The remaining three eyes deteriorated by two or more lines in the Snellen chart due to the progression of cataract, chronic cystoid macular edema, and glaucomatous optic atrophy, respectively. Conclusions: The results of this study suggest that pars plana vitrectomy may have a beneficial effect on the course of uveitis and the associated complications of cystoid macular edema, thereby reducing the need for long-term immunosuppression. Pars plana vitrectomy combined with simultaneous cataract surgery can improve the visual outcome in these patients.
C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Serv Immunol, Boston, MA 02114 USA.
RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Serv Immunol, 243 Charles St, Boston, MA 02114 USA.
NR 27
TC 16
Z9 19
U1 0
U2 0
PU SWETS ZEITLINGER PUBLISHERS
PI LISSE
PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD SEP
PY 2001
VL 9
IS 3
BP 141
EP 151
DI 10.1076/ocii.9.3.141.3965
PG 11
WC Ophthalmology
SC Ophthalmology
GA 505FJ
UT WOS:000172902500003
PM 11815883
ER

PT J
AU Akpek, EK
   Baltatzis, S
   Yang, J
   Foster, CS
AF Akpek, EK
   Baltatzis, S
   Yang, J
   Foster, CS
TI Long-term immunosuppressive treatment of serpiginous choroiditis
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Article
DE serpiginous choroiditis; long-term treatment; immunosuppression
ID LOW-DOSE CYCLOSPORINE; INTRAOCULAR INFLAMMATORY DISEASE;
   BEHCETS-SYNDROME; CLINICAL COURSE; THERAPY; UVEITIS; AZATHIOPRINE;
   NEOVASCULARIZATION; CHOROIDOPATHY; SCLERITIS
AB Objective: To determine the efficacy of immunosuppressive treatment in serpiginous choroiditis. Design: The clinical courses were reviewed of six consecutive patients (12 eyes) with vision-threatening, steroid-dependent/resistant serpiginous choroiditis treated with a combination of immunosuppressive agents including azathioprine, cyclosporine, and cyclophosphamide. All patients underwent treatment for at least 12 months. Results: The follow-up period ranged from 17 to 105 months (mean 57, median 43). All patients were able to taper oral steroids. Five patients discontinued all immunosuppressive medications after a treatment period of 12 to 69 months (mean 39 months). Immunosuppressive treatment was continued in one patient at a 'low' maintenance dose. Ten eyes had improved visual acuities, while vision remained impaired in two due to macular scars. Recurrence was noted in two patients when an attempt was made to decrease the dose of immunosuppressive medication. Two patients experienced side effects which were reversed by decreasing the dose of the medications. Conclusion: Long-term immunosuppressive treatment appears to prolong remission and preserve vision in patients with serpiginous choroiditis.
C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA.
   Univ Athens, Dept Ophthalmol, Athens, Greece.
RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol Serv, 243 Charles St, Boston, MA 02114 USA.
NR 55
TC 19
Z9 20
U1 0
U2 0
PU SWETS ZEITLINGER PUBLISHERS
PI LISSE
PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD SEP
PY 2001
VL 9
IS 3
BP 153
EP 167
DI 10.1076/ocii.9.3.153.3962
PG 15
WC Ophthalmology
SC Ophthalmology
GA 505FJ
UT WOS:000172902500004
PM 11815884
ER

PT J
AU Uy, HS
   Christen, WG
   Foster, CS
AF Uy, HS
   Christen, WG
   Foster, CS
TI HLA-B27-associated uveitis and cystoid macular edema
SO OCULAR IMMUNOLOGY AND INFLAMMATION
LA English
DT Article
DE uveitis; HLA-B27; cystoid macular edema; vitreous cells
ID ACUTE ANTERIOR UVEITIS; BLOOD-RETINAL BARRIER; EXPERIMENTAL AUTOIMMUNE
   UVEORETINITIS; CLINICAL-FEATURES; INTRAOCULAR INFLAMMATION; HLA-B27;
   PERMEABILITY; ALPHA
AB Objective: To determine which ocular and systemic characteristics are associated with cystoid macular edema (CME) in patients with HLA-B27-associated uveitis. Methods: The authors reviewed the records of 129 patients (157 eyes) with HLA-B27-associated uveitis seen at the Massachusetts Eye and Ear Infirmary from June 1980 to June 1995. Data obtained from the records included: age, gender, duration of uveitis, follow-up duration, ocular and systemic findings, presence of CME, therapeutic intervention, and visual outcome. Results: Twenty-one of 157 eyes (13.4%) with HLA-B27-associated uveitis presented with or subsequently developed CME. In 14 (67%) eyes with CME, vitreous cells were noted either at presentation or during follow-up. Forty-nine of 136 eyes (36%) without CME had vitreous cells at presentation or developed vitreous cells during follow-up. The estimated odds ratio for developing CME associated with the presence of vitreous cells was 2.9 (95% confidence interval: 1.0-8.3). No other demographic, ocular, or systemic characteristics appeared to be associated with the presence of CME. Conclusion:The presence of vitreous cells in patients with HLA-B27-associated uveitis may indicate an increased risk of CME development.
C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA.
   Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA.
NR 24
TC 11
Z9 14
U1 0
U2 0
PU SWETS ZEITLINGER PUBLISHERS
PI LISSE
PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS
SN 0927-3948
J9 OCUL IMMUNOL INFLAMM
JI Ocul. Immunol. Inflamm.
PD SEP
PY 2001
VL 9
IS 3
BP 177
EP 183
DI 10.1076/ocii.9.3.177.3963
PG 7
WC Ophthalmology
SC Ophthalmology
GA 505FJ
UT WOS:000172902500006
PM 11815886
ER

PT J
AU Barker, FG
AF Barker, FG
TI Considerations in the diagnosis and management of brain metastases - The
   Sawaya article reviewed
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID PROPHYLACTIC CRANIAL IRRADIATION; CELL LUNG-CANCER; TUMORS
C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA.
RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA.
NR 8
TC 0
Z9 0
U1 0
U2 0
PU P R R INC
PI MELVILLE
PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD SEP
PY 2001
VL 15
IS 9
BP 1158
EP +
PG 2
WC Oncology
SC Oncology
GA 525LA
UT WOS:000174070500013
ER

EF