FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rutecki, PA Yang, YL AF Rutecki, PA Yang, YL TI Ictal epileptiform activity in the CA3 region of hippocampal slices produced by pilocarpine SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ELECTROGRAPHIC SEIZURES; ENTORHINAL CORTEX; EXTRACELLULAR POTASSIUM; GABAERGIC INTERNEURONS; RAT HIPPOCAMPUS; PYRAMIDAL CELLS; THETA-RHYTHM; IN-VITRO; NEURONS; EXCITATION AB Pilocarpine, a muscarinic agonist, produces status epilepticus that is associated with the later development of chronic recurrent seizures. When applied to rat hippocampal slices, pilocarpine (10 mu M) produced brief (<200 ms) epileptiform discharges that resembled interictal activity that occurs between seizures, as well as more prolonged synchronous neuronal activation that lasted seconds (3-20 s), and was comparable to ictal or seizures-like discharges. We assessed the factors that favored ictal patterns of activity and determined the biophysical properties of the ictal discharge. The probability of observing ictal discharges was increased when extracellular potassium ([K+](o)) was increased from 5 to 7.5 mM. Raising [K+](o) to 10 mM resulted in loss of ictal patterns and, in 20 of 34 slices, desynchronization of epileptiform activity. Making the artificial cerebrospinal fluid (ACSF) hyposmotic favored ictal discharges at 5 mM [K+](o), but shifted 7.5 mM [K+](o) ACSF patterns to interictal discharges or desynchronized activity. Conversely, increasing osmolality suppressed ictal patterns. The pilocarpine-induced ictal discharges were blocked by atropine (1 mu M, n = 5), a muscarinic antagonist, and pirenzepine (1 mu M, n = 6), a selective MI receptor antagonist. Kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor blockade stopped all epileptiform activity (n = s).The N-methyl-D-aspartate antagonist D,L-2-amino-5-phosphonovaleric acid (100 mu M, n = 34) did not change the pattern of epileptiform activity but significantly increased the rate of interictal discharges and prolonged the duration of ictal discharges. The ictal discharge was characterized intracellularly by a depolarization that was associated with action potential generation and persisted as a membrane oscillation of 4-10 Hz. The ictal oscillations reversed in polarity at -22.7 +/- 2.2 mV (n = 11) with current-clamp recordings and -20.9 +/- 3.1 mV (n = 7) with voltage-clamp recordings. The reversal potential of the ictal discharge in the presence of the gamma-aminobutyric acid-A blocker bicuculline (10 mu M, n = 6) was -2.2 +/- 2.6 mV and was significantly different from that measured without bicuculline. Bicuculline added to 7.5 mM [K+](o) and 10 mu M pilocarpine did not cause epileptiform activity to change pattern but significantly increased the rate of interictal discharges and prolonged the ictal discharge duration. Both synaptic and nonsynaptic mechanisms are important for the generation of ictal patterns of epileptiform activity. Although the synchronous epileptiform activity produced by pilocarpine required fast glutamate-mediated synaptic transmission, the transition from an interictal to ictal pattern of activity depended on [K+](o) and could be influenced by extracellular space. C1 Univ Wisconsin, Sch Med, William S Middleton Mem Vet Adm Hosp, Dept Neurol, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, William S Middleton Mem Vet Adm Hosp, Dept Neurosurg, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, William S Middleton Mem Vet Adm Hosp, Dept Neurosci,Training Program, Madison, WI 53705 USA. RP Rutecki, PA (reprint author), Univ Wisconsin, Sch Med, William S Middleton Mem Vet Adm Hosp, Dept Neurol Neurosurg & Neurosci,Training Program, 2500 Overlook Tr, Madison, WI 53705 USA. FU NINDS NIH HHS [NS-28580] NR 46 TC 29 Z9 30 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1998 VL 79 IS 6 BP 3019 EP 3029 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZV958 UT WOS:000074359400017 PM 9636105 ER PT J AU Brown, MC Kujawa, SG Duca, ML AF Brown, MC Kujawa, SG Duca, ML TI Single olivocochlear neurons in the guinea pig. I. Binaural facilitation of responses to high-level noise SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID AUDITORY-NERVE FIBERS; ELECTRICAL-STIMULATION PARAMETERS; PRODUCT OTOACOUSTIC EMISSIONS; COMPOUND ACTION-POTENTIALS; CONTRALATERAL SOUND; COCHLEAR EFFERENT; ACOUSTIC STIMULATION; MASKED TONES; BUNDLE; DEPENDENCE AB Single medial olivocochlear (MOC) neurons were recorded from the cochlea of the anesthetized guinea pig. We used tones and noise presented monaurally and binaurally and measured responses for sounds up to 105 dB sound pressure level (SPL). For monaural sound, MOC neuron firing rates were usually higher for noise bursts than tone bursts, a situation not observed for afferent fibers of the auditory nerve that were sampled in the same preparations. MOC neurons also differed from afferent fibers in having less saturation of response. Some MOC neurons had responses that continued to increase even at high sound levels. Differences between MOC and afferent responses suggest that,there is convergence in the pathway to olivocochlear neurons, possibly a combination of inputs that are at the characteristic frequency (CF) with others that are off the CF. Opposite-ear noise almost always facilitated the responses of MOC neurons to sounds in the main ear, the ear that best drives the unit. This binaural facilitation depends on several characteristics that pertain to the main ear: it is higher in neurons having a contralateral main ear (contra units), it is higher at main-ear sound levels that are moderate (similar to 65 dB SPL), and it is higher in neurons with low discharge rates to main-ear stimuli. Facilitation also depends on parameters of the opposite-ear sound: facilitation increases with noise level in the opposite ear until saturating, is greater for continuous noise than noise bursts, and is usually greater for noise than for tones. Using optimal opposite-ear facilitators and high-level stimuli, the firing rates of olivocochlear neurons range up to 140 spikes/s, whereas for moderate-level monaural stimuli the rates are <80 spikes/s. At hi,oh sound levels, firing rates of olivocochlear neurons increase with CF, an increase that may compensate for the known lower effectiveness of olivocochlear synapses on outer hair cells responding to high frequencies. Overall, our results demonstrate a high MOC response for binaural noise and suggest a prominent role for the MOC system in environments containing binaural noise of high level. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA 02114 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC-00180, DC-01089] NR 52 TC 28 Z9 28 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1998 VL 79 IS 6 BP 3077 EP 3087 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZV958 UT WOS:000074359400021 PM 9636109 ER PT J AU Brown, MC Kujawa, SG Liberman, MC AF Brown, MC Kujawa, SG Liberman, MC TI Single olivocochlear neurons in the guinea pig. II. Response plasticity due to noise conditioning SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MIDDLE-EAR MUSCLES; REDUCES AUDITORY DESENSITIZATION; RECEPTIVE-FIELD PLASTICITY; INDUCED HEARING-LOSS; EFFERENT NEURONS; THRESHOLD SHIFT; ELECTRICAL-STIMULATION; COCHLEAR EFFERENTS; SPONTANEOUS RATES; NERVE RESPONSE AB Previous studies have shown that daily, moderate-level sound exposure, or conditioning, can reduce injury from a subsequent high-level noise exposure. We tested the hypothesis that this conditioning produces an increased activity in the olivocochlear efferent reflex, a reflex known to provide protection to the cochlea. Guinea pigs were conditioned by a 10-day intermittent exposure to 2-4 kHz noise at 85 dB sound pressure level. This conditioning is known to reduce damage from a subsequent high-level exposure to the same noise band. Responses to monaural and binaural sound were recorded from single medial olivocochlear (MOC) efferent neurons, and data from conditioned animals were compared with those obtained from unexposed controls. MOC neurons were classified by their response to noise bursts in the ipsilateral or contralateral ears as ipsi units, contra units, or either-ear units. There were no significant differences in the distributions of these unit types between control and conditioned animals. There were also no differences in other responses to monaural stimuli, including the distribution of characteristic frequencies (CFs), the sharpness of tuning, or thresholds at the CF. For binaural sound at high levels, particularly relevant to sound-evoked activation of the MOC reflex during acoustic overstimulation, the firing rates of MOC neurons with CFs just above the conditioning band showed slight (but statistically significant) elevations relative to control animals. Frequency regions just above the conditioning band also demonstrated maximum conditioning-related protection; thus protection could be due, in part, to long-term changes in MOC discharge rates. For binaural sound at low levels, MOC firing rates in conditioned animals also were increased significantly relative to controls. Again, increases were largest for neurons with CFs just above the conditioning band. For equivalent monaural sound, rates were not significantly increased; thus, conditioning appears to increase binaural facilitation by opposite-ear sound. These data indicate that MOC neurons show long-term plasticity in acoustic responsiveness that is dependent on their acoustic history. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, Boston, MA 02114 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC-00188, DC-01089, DC-00180] NR 55 TC 26 Z9 27 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1998 VL 79 IS 6 BP 3088 EP 3097 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZV958 UT WOS:000074359400022 PM 9636110 ER PT J AU Levy, ML Cummings, JL Fairbanks, LA Masterman, D Miller, BL Craig, AH Paulsen, JS Litvan, I AF Levy, ML Cummings, JL Fairbanks, LA Masterman, D Miller, BL Craig, AH Paulsen, JS Litvan, I TI Apathy is not depression SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; POSITRON EMISSION; DIAGNOSIS; DEMENTIA; RELIABILITY; CRITERIA; VALIDITY; SCALE AB If depression is associated with apathy, then they should be expressed together in different dementia syndromes and should co-occur at varying levels of disease severity. The authors performed a cross-sectional comparison of neuropsychiatric symptoms in 30 Alzheimer's disease, 28 frontotemporal dementia, 40 Parkinson's disease, 34 Huntington's disease, and 22 progressive supranuclear palsy patients, using a standardized rating scale (the Neuropsychiatric Inventory). Apathy did not correlate with depression in the combined sample; apathy (r = -0.40, P<0.0001), but not depression, correlated with lower cognitive function as measured by the Mini-Mental State Examination. The relationship of apathy to depression also varied across diagnostic groups. Apathy is a specific neuropsychiatric syndrome that is distinct from depression. Distinguishing these two syndromes has therapeutic implications. C1 Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. Harbor Univ Calif Los Angeles Med Ctr, Los Angeles, CA USA. Univ Iowa, Coll Med, Dept Psychiat, Iowa City, IA 52242 USA. NINDS, Bethesda, MD 20892 USA. RP Cummings, JL (reprint author), Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Psychiat & Biobehav Sci, 710 Westwood Pl, Los Angeles, CA 90095 USA. OI Litvan, Irene/0000-0002-3485-3445 FU NIA NIH HHS [AG10123] NR 37 TC 333 Z9 343 U1 2 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1998 VL 10 IS 3 BP 314 EP 319 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 106GJ UT WOS:000075121300007 PM 9706539 ER PT J AU Bondareff, W Matsuyama, SS Dell'Albani, P AF Bondareff, W Matsuyama, SS Dell'Albani, P TI Production of paired helical filament, tau-like proteins by PC12 cells: A model of neurofibrillary degeneration SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE tau; Alzheimer's disease; neurofibrillary degeneration ID ALZHEIMERS-DISEASE; ABNORMAL PHOSPHORYLATION; TANGLES; LOCALIZATION; DETERMINANTS; PATHOLOGY; DEMENTIA; ISOFORMS; EPITOPE; KINASE AB Neuron-like cells derived from a rat pheochronaocytoma cell line (PC12) and differentiated with nerve growth factor produce a paired helical filament (PRF)like antigen when they are subjected to heat shock (Wallace et al,: Mol Brain Res 19:149-155, 1993), Tt accumulates in a localized region of the perinuclear cytoplasm and reacts with monoclonal antitau antibodies, which identify epitopes in the N- and C-terminal halves and the microtubule-binding domain of tau protein. The observed profile of immunoreactivity suggests the presence of full-length and C-terminally truncated tau in a region of perinuclear cytoplasm in which no structurally intact PHFs could be demonstrated by conventional transmission electron microscopy. The accumulated tan protein colocalized with antibodies raised against mitochondrial outer membrane proteins and was associated with the presence of numerous mitochondrial profiles that were demonstrated with electron microscopy, Because differentiated PC12 cells pretreated with colcemid or Taxol prior to heat shock fail to exhibit perinuclear PNF-like immunoreactivity, the reported response to heat shock appears to require an intact system of intracellular microtubules. This PC12 system provides a model in which the metabolic and molecular biological underpinnings of neuronal degeneration in Alzheimer's disease can be manipulated. The system may eventually be applicable to the development of pharmaceutical agents that interfere with formation and/or degeneration of PHF-tau in Alzheimer's disease. (C) 1998 Wiley-Liss, Inc. C1 Univ So Calif, Sch Med, Dept Psychiat & Behav Sci, Div Geriatr Psychiat, Los Angeles, CA 90033 USA. W Los Angeles Vet Affairs Med Ctr, Brentwood Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA. RP Bondareff, W (reprint author), Univ So Calif, Sch Med, Dept Psychiat, Div Geriatr Psychiat, Hlth Sci Campus,MOL-202, Los Angeles, CA 90033 USA. RI Dell'Albani, Paola/B-7781-2015 OI Dell'Albani, Paola/0000-0003-4349-0276 NR 45 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 1 PY 1998 VL 52 IS 5 BP 498 EP 504 DI 10.1002/(SICI)1097-4547(19980601)52:5<498::AID-JNR2>3.3.CO;2-M PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZQ760 UT WOS:000073900300002 PM 9632306 ER PT J AU Furukawa, KS Guo, Q Schellenberg, GD Mattson, MP AF Furukawa, KS Guo, Q Schellenberg, GD Mattson, MP TI Presenilin-1 mutation alters NGF-induced neurite outgrowth, calcium homeostasis, and transcription factor (AP-1) activation in PC12 cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Alzheimer's disease; apoptosis; c-fos; endoplasmic reticulum; fura-2; growth cones; inositol trisphosphate; voltage-dependent calcium channels ID NERVE-GROWTH-FACTOR; FAMILIAL ALZHEIMERS-DISEASE; GENE-EXPRESSION; IN-VIVO; NEURONS; DIFFERENTIATION; PATHWAYS AB Mutations in the presenilin-1 (PS-1) gene are responsible for many cases of autosomal dominant early-onset inherited Alzheimer's disease (AD), PS-1 is expressed in neurons where it is localized primarily to the endoplasmic reticulum (ER); the normal function of PS-1 and its pathogenic mechanism in AD are not known, We now report that expression of an AD-linked human PS-1 mutation (L286V) in PC12 cells results in aberrant differentiation responses to nerve growth factor (NGF). The extent of neurite outgrowth during a 10-day period of exposure to NGF was significantly reduced In lines stably expressing mutant PS-1. NGF induced a prolonged elevation of intracellular calcium levels which was significantly enhanced in cells expressing mutant PS-1. Induction of DNA binding activity of the transcription factor AP-1 by NGF was markedly suppressed in cells expressing mutant PS-1. Collectively, these findings demonstrate that a PS-1 mutation alters cellular signaling systems associated with NGF-induced differentiation in PC12 cells. Altered responsivity to neurotrophic factors could play a role in the pathogenesis of neuritic degeneration and cell death in human carriers of PS-1 mutations. (C) 1998 Wiley-Liss, Inc. C1 Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA USA. Univ Washington, Dept Pharmacol, Seattle, WA USA. RP Mattson, MP (reprint author), Univ Kentucky, Sanders Brown Res Ctr Aging, 211 Sanders Brown Bldg, Lexington, KY 40536 USA. EM mmattson@aging.coa.uky.edu RI Mattson, Mark/F-6038-2012 FU NIA NIH HHS [AG05119, AG05144, AG14554] NR 38 TC 47 Z9 47 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 1 PY 1998 VL 52 IS 5 BP 618 EP 624 DI 10.1002/(SICI)1097-4547(19980601)52:5<618::AID-JNR14>3.0.CO;2-Y PG 7 WC Neurosciences SC Neurosciences & Neurology GA ZQ760 UT WOS:000073900300014 PM 9632318 ER PT J AU Westmoreland, SV Halpern, E Lackner, AA AF Westmoreland, SV Halpern, E Lackner, AA TI Simian immunodeficiency virus encephalitis in rhesus macaques is associated with rapid disease progression SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE AIDS; HIV encephalitis; epidemiology; neurovirulence ID INDUCED AIDS ENCEPHALITIS; CENTRAL-NERVOUS-SYSTEM; CELLULAR-LOCALIZATION; VIRAL REPLICATION; LYMPHOID-TISSUES; HIV-INFECTION; MONKEYS; SIV; PATHOGENESIS; EXPRESSION AB Central nervous system (CNS) disease is a major feature of simian immunodeficiency virus (SIV) infection of macaques. To define the spectrum of CNS lesions in SIV-infected macaques and the potential associations with viral strain and disease course, we performed a retrospective analysis of necropsies on 124 macaques with SIV-induced AIDS. Histologic evidence of CNS disease was observed in 71 (57.3%) of the 124 animals. SIV encephalitis was the most common CNS lesion occurring in 43.7% (31/71) of the animals with CNS disease and 25% of all animals. The incidence of SIVE correlated significantly with shortened survival (P=0.0207). In addition, SIVE was seen in 42.9% (15/35) of rapid progressors (animals that died within 200 days) compared to only 18% (16/89) of normal progressors (animals that lived longer than 200 days) (P=0.011). Animals with SIVE had higher viral loads in peripheral blood than those that did not, but this difference did not reach statistical significance. Similarly, while animals infected with uncloned SIVmac251 had a higher incidence of SIVE (27.5%; 14/51) than animals infected with molecularly cloned SIVmac239 and its T-cell tropic derivatives (18.5%; 10/54) this difference was not statistically significant. In this study rapid disease progression and SIVE were highly correlated making separation of viral determinants of virulence from those of neurovirulence difficult. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, CIPR, Charlestown, MA 02129 USA. RP Lackner, AA (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. FU NINDS NIH HHS [NS30769, NS35732, NS33820] NR 37 TC 84 Z9 84 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 1998 VL 4 IS 3 BP 260 EP 268 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA ZQ961 UT WOS:000073920700003 PM 9639069 ER PT J AU Shi, B Raina, J Lorenzo, AE Busciglio, J Gabuzda, D AF Shi, B Raina, J Lorenzo, AE Busciglio, J Gabuzda, D TI Neuronal apoptosis induced by HIV-1 Tat protein and TNF-alpha: potentiation of neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE apoptosis; brain; central nervous system; HIV-1; Tat; TNF-alpha ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; POLYMERASE CHAIN-REACTION; CORTICAL CELL-CULTURES; CENTRAL-NERVOUS-SYSTEM; METHYL-D-ASPARTATE; AIDS DEMENTIA; NEOCORTICAL DAMAGE; BASIC DOMAIN; HUMAN BRAIN AB Apoptosis of neurons and non-neuronal cells has been demonstrated in the brain of AIDS patients with dementia. Previous studies suggest that the apoptotic stimuli are likely to be soluble factors. Several candidates for the soluble factors that lead to neuronal apoptosis in HIV-1 infection have been proposed, including the HIV-1 Tat protein and TNF-alpha. The mechanisms that lead to neuronal apoptosis in the brain of AIDS patients in vivo, may involve the combined effects of more than one pro-apoptotic factor. In this study, we examine whether exposure of primary human neurons to the combination of HIV-1 Tat and TNF-alpha can potentiate the induction of neuronal apoptosis compared with exposure to either factor alone. TNF-alpha was shown to potentiate the induction of neuronal apoptosis by HIV-1 Tat via a mechanism that involves increased oxidative stress. Antioxidants inhibited, but did not completely abolish the induction of neuronal apoptosis by Tat, suggesting that other mechanisms are also likely to be involved. These findings suggest that soluble HIV-1 Tat and TNF-alpha may play a role in neuronal apoptosis induced by HIV-1 infection of the CNS, particularly when present in combination. Our findings further suggest that one mechanism whereby combinations of pro-apoptotic factors may potentiate the induction of neuronal apoptosis in the brain of AIDS patients is by increasing oxidative stress. Understanding the role of oxidative stress and other mechanisms that lead to apoptosis in HIV-1 infection of the CNS may advance the development of new therapeutic strategies to prevent neuronal cell death and improve neurologic function in AIDS patients. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Immunodiagnost Inc, Bedford, MA 01730 USA. Childrens Hosp, Med Ctr, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. FU NIAID NIH HHS [AI28691]; NINDS NIH HHS [NS35734] NR 56 TC 144 Z9 149 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 1998 VL 4 IS 3 BP 281 EP 290 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA ZQ961 UT WOS:000073920700005 PM 9639071 ER PT J AU Jones, K Johnson, KA Becker, JA Spiers, PA Albert, MS Holman, BL AF Jones, K Johnson, KA Becker, JA Spiers, PA Albert, MS Holman, BL TI Use of singular value decomposition to characterize age and gender differences in SPECT cerebral perfusion SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE SPECT; technetium-99m hexamethyl propyleneamine oxime; aging; gender differences ID POSITRON EMISSION TOMOGRAPHY; GLUCOSE-UTILIZATION; ALZHEIMERS-DISEASE; SEX-DIFFERENCES; METABOLISM; PATTERNS; ATROPHY; VOLUME; CAMERA; STATE AB The main objective of this study was to characterize changes in brain perfusion associated with normal aging and gender. Methods: Perfusion SPECT images using Tc-99m-hexamethyl propyleneamine oxime (HMPAO) were obtained from 152 healthy subjects (67 men, 85 women) aged 50-92 yr. An automated method was developed to objectively assess image data from a large number of brain regions. Image data were reduced with singular value decomposition (SVD), which produced 20 eigenvectors capturing 97.05% of the total information content of 4320 regions from each subject. Subjects were scored individually on each vector. Results: Multivariate analyses demonstrated that there were no significant differences in whole-brain HMPAO uptake with age, but age-related regional declines were seen in lateral ventricular regions. Women had higher HMPAO uptake than men in estimates of global perfusion and regional perfusion in the midcingulate/corpus callosum, inferior temporal and inferior parietal areas. Conclusion: These discriminations demonstrate that singular value deomposition of SPECT data may be used to assess differences in perfusion patterns between groups of subjects. They replicate several previous findings, both with respect to age-related changes in perfusion and with respect to gender differences. In addition, they identify a previously unreported gender difference in biparietal regions. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Brandeis Univ, Florence Heller Sch Adv Studies Social Welf, Waltham, MA 02254 USA. RP Albert, MS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychiat Gerontol 149-9124,Bldg 149 13th St, Charlestown, MA 02129 USA. NR 43 TC 36 Z9 36 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUN PY 1998 VL 39 IS 6 BP 965 EP 973 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZR993 UT WOS:000074036900014 PM 9627327 ER PT J AU Bate, GW Varro, A Dimaline, R Wang, TC Koh, TJ Dockray, GJ AF Bate, GW Varro, A Dimaline, R Wang, TC Koh, TJ Dockray, GJ TI Control of entero chromaffin-like (ECL) cell function in transgenic mice expressing gastrin in pancreatic beta-cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract C1 Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUN PY 1998 VL 509P SI SI BP 10P EP 10P PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZZ634 UT WOS:000074750300011 ER PT J AU Shimada, SD Robertson, RN Bonninger, ML Cooper, RA AF Shimada, SD Robertson, RN Bonninger, ML Cooper, RA TI Kinematic characterization of wheelchair propulsion SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE biomechanics; kinematics; kinetics; stroke patterns; wheelchairs ID INDUSTRY; KINETICS AB Rehabilitation scientists and biomedical engineers have been investigating wheelchair propulsion biomechanics in order to prevent musculoskeletal injuries. Several studies have investigated wheelchair propulsion biomechanics; however, few have examined wheelchair propulsion stroke patterns. The purpose of this study was to characterize wheelchair propulsion stroke patterns by investigating joint accelerations, joint range of motions, wheelchair propulsion phases, and stroke efficiency. Seven experienced wheelchair users (5 males, 2 females) were filmed using a three-camera motion analysis system. Each subject pushed a standard wheelchair fitted with a force-sensing pushrim (SMART(Wheel)) at two speeds (1.3 and 2.2 m/s). The elbow angle was analyzed in the sagittal plane, while the shoulder joint was analyzed in the sagittal and frontal planes. Three distinctly different stroke patterns: semi-circular (SC), single looping-over-propulsion (SLOP), and double looping-over-propulsion (DLOP), were identified from the kinematic analysis. Through our analysis of these patterns, we hypothesized that SC was more biomechanically efficient than the other stroke patterns. Future studies using a larger number of subjects and strokes may reveal more significant distinctions in efficiency measures between stroke patterns. C1 Univ Pittsburgh, Med Ctr, Div Phys Med & Rehabil, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Pittsburgh, PA 15206 USA. RP Shimada, SD (reprint author), VA Med Ctr 151-RI, Human Engn Res Lab, Highland Dr, Pittsburgh, PA 15206 USA. EM shimadas@hhsserver.hhs.csus.edu NR 27 TC 46 Z9 47 U1 1 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUN PY 1998 VL 35 IS 2 BP 210 EP 218 PG 9 WC Rehabilitation SC Rehabilitation GA ZV685 UT WOS:000074330700008 PM 9651893 ER PT J AU Goldstein, G Beers, SR Shemansky, WJ Longmore, S AF Goldstein, G Beers, SR Shemansky, WJ Longmore, S TI An assistive device for persons with severe amnesia SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE amnesia; assistive devices; memory ID MEMORY-IMPAIRED PATIENTS; RETENTION; ACQUISITION; KNOWLEDGE AB Five persons with severe amnesia were trained to use a device containing items of information relevant to daily activities. The training consisted of a procedure in which requests for information were paired with a tone, and the subject was required to access the device and respond with the answer to the request. The tone was gradually faded, with the goal of having the subject respond to a question alone. All of the subjects learned to consistently access the device and provide correct responses following a request for information. Generalization across requesters and settings in which the requests were made was also achieved. The findings are discussed in regard to the utility of exploiting the relatively well-preserved procedural memory system for rehabilitation of persons with severe amnesia. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15261 USA. RP Goldstein, G (reprint author), VA Med Ctr 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 20 TC 12 Z9 12 U1 0 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUN PY 1998 VL 35 IS 2 BP 238 EP 244 PG 7 WC Rehabilitation SC Rehabilitation GA ZV685 UT WOS:000074330700012 PM 9651897 ER PT J AU Randell, AG Bhalerao, N Nguyen, TV Sambrook, PN Eisman, JA Silverman, SL AF Randell, AG Bhalerao, N Nguyen, TV Sambrook, PN Eisman, JA Silverman, SL TI Quality of life in osteoporosis: Reliability, consistency, and validity of the osteoporosis assessment questionnaire SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE quality of life; reliability; statistics; osteoporosis ID IMPACT MEASUREMENT SCALES; MEASURING HEALTH-STATUS; OF-LIFE; FRACTURES; ARTHRITIS AB Objective. To determine the reliability, consistency, and clinical utility of the Osteoporosis Assessment Questionnaire (OPAQ), an AIMS2 based self-assessment questionnaire. Methods. Reliability of individual questions, scales, and domains were evaluated in 40 subjects by test-retest and intraclass correlation coefficients and internal consistency by Cronbach's alpha. Construct validity was evaluated by disease state. The relationships between domains and scales were modeled by confirmatory factor analysis. Results. Mean kappa (79 questions) and intraclass correlation (18 health scales) coefficients were 0.58 +/- 0.16 (mean +/- SD) and 0.82 +/- 0.07, respectively. Internal consistency was greater than 0.8 in all but 3 scales. Construct validity was confirmed. Patients with hip fracture recorded lower OPAQ scores than patients with vertebral fracture. Correlation and confirmatory factor analyses grouped the 18 health scales into 7 domains. Conclusion. These findings suggest that OPAQ is a reliable, consistent, and valid instrument capable of distinguishing hierarchy of functional loss in disease states in osteoporosis. C1 St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Program, Sydney, NSW 2010, Australia. Royal N Shore Hosp, Dept Rheumatol, St Leonards, NSW 2065, Australia. W Los Angeles Vet Adm Hosp, Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Randell, AG (reprint author), St Vincents Hosp, Garvan Inst Med Res, Bone & Mineral Res Program, 384 Victoria St, Sydney, NSW 2010, Australia. EM a.randell@garvan.unsw.edu RI Nguyen, Tuan/B-6147-2008; Eisman, John/C-2886-2014 OI Nguyen, Tuan/0000-0002-3246-6281; NR 20 TC 65 Z9 68 U1 3 U2 5 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 1998 VL 25 IS 6 BP 1171 EP 1179 PG 9 WC Rheumatology SC Rheumatology GA ZQ554 UT WOS:000073879700024 PM 9632082 ER PT J AU Easson, AM Bode, BP Fischer, CP Souba, WW AF Easson, AM Bode, BP Fischer, CP Souba, WW TI Effects of endotoxin challenge on hepatic amino acid transport during cancer SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE endotoxin; cancer; amino acid transport; liver; glutamine ID TUMOR-NECROSIS-FACTOR; BONE-MARROW TRANSPLANTATION; TOTAL PARENTERAL-NUTRITION; PLASMA-MEMBRANE VESICLES; ISOLATED RAT HEPATOCYTES; GLUTAMINE-METABOLISM; SKELETAL-MUSCLE; ADAPTIVE REGULATION; HORMONAL-REGULATION; PROTEIN-METABOLISM AB Background. The hepatic uptake of amino acids is increased in both sepsis and cancer, and this response appears to be both global and essential in the catabolic host. Because immunocompromised cancer patients are susceptible to episodes of gram-negative sepsis, we examined the capacity of hepatocytes from normal and tumor-influenced livers to respond to the additional challenge of endotoxemia via increases in the Na+-dependent uptake of glutamine and zwitterionic amino acids by System N and System A, respectively. Materials and methods. Fischer 344 rats were implanted with methylcholanthrene-induced fibrosarcomas. Control rats were sham-operated and pair-fed. Animal pairs (tumor burden = 8-32% carcass weight) were injected intraperitoneally with either Escherichia coli endotoxin (10 mg/kg) or PBS, and after 4 h, hepatocytes were isolated from the livers of the animals via collagenase perfusion and placed in primary culture. Three hours later, amino acid transport rates were measured using radiolabeled glutamine for System N and alpha-methylaminoisobutyric acid (MeAIB), a nonmetabolizable substrate specific for System A. Results. Cancer - independent of tumor size - and endotoxin each elicited similar 1.5- to 2-fold inductions of System N activity. When combined, their effects mere additive rather than synergistic. In contrast, endotoxin induced an insignificant increase in System A activity, whereas cancer stimulated this carrier 2-fold in either the-absence or the presence of endotoxin. Conclusions. The primary glutamine and alanine carriers in hepatocytes are differentially influenced during catabolic states, and the tumor-influenced liver is competent to further increase glutamine uptake in response to additional catabolic insults. (C) 1998 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Easson, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. FU NCI NIH HHS [CA57690] NR 43 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 EI 1095-8673 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1998 VL 77 IS 1 BP 29 EP 34 DI 10.1006/jsre.1998.5323 PG 6 WC Surgery SC Surgery GA 108LH UT WOS:000075267500006 PM 9698528 ER PT J AU Roesler, JM Livingston, EH Srivatsan, E Chang, P Wang, MB AF Roesler, JM Livingston, EH Srivatsan, E Chang, P Wang, MB TI Deletion of P15 (MTS2) in head and neck squamous cell carcinomas SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE p15; MTS2; head and neck cancer; squamous cell carcinoma ID TUMOR-SUPPRESSOR GENES; HOMOZYGOUS DELETIONS; FREQUENT; CYCLE; CDKN2; P15(INK4B)/MTS2; PROGRESSION; CANCER; BRAIN; LINES AB Introduction. The purpose of this study was to determine whether the multiple tumor suppressor 2 (MTS2) gene, encoding an inhibitor (p15) of cyclin D-dependent kinases 4 and 6 (cdk4, cdk8), is deleted in head and neck squamous cell carcinomas (HNSCC). There is a high frequency of LOH for the 9p21-p22 region in HNSCCs, as well as in gliomas, leukemias, and cell lines from multiple tumor types; thus, this region is suspected to contain a tumor suppressor gene or genes. P16 (MTS1), an inhibitor of cdk4 and cdk6, resides within the deleted 9p21 region in these tumors. A neighboring gene, p15 (MTS2), has biochemical properties similar to those of p16, but has not been characterized in HNSCC. Methods. Twenty-one head and neck squamous cell carcinomas and their proximal margins were snap frozen at the time of surgical resection. DNA isolation was performed using standard phenol and chloroform extraction. Standard PCR methods were used with primers P15-1F and P15-1R, specific for exon 1 of the p15 gene, as described previously. All samples were amplified for beta-Globin as a positive control. PCR products were stained with ethidium bromide and run on 6% polyacrylamide gels. Expected sizes for the PCR products were p15, 532 bp, and beta-globin, 238 bp. Results. Of 21 proximal margins, all demonstrated normal amplification of p15 DNA, all having a visible 532bp PCR product. Of 21 HNSCC tumors, 9 showed no amplification of the p15 gene; none of these 9 neoplasms had visible PCR products. All proximal margins and head and neck squamous cell carcinomas demonstrated amplification of the beta-globin gene, indicating that the DNA used was of good quality. Conclusions. Although PCR is not a quantitative technique, densitometric analysis of PCR products showed it was unlikely that the p15 gene was present in more than a small fraction of the tumor cells. The amount of the p15 PCR product in these cells was less than 3% of that observed in reactions containing an equal amount of DNA from normal cells. We are the first to show an absence of normal p15 exon 1 gene amplification in nearly 50% of HNSCCs studied. Loss of the MTS2 gene product, p15, may contribute to the loss of cell cycle and growth regulation seen in HNSCC. (C) 1998 Academic Press. C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Div Head & Neck Surg,Mol Biol Res Lab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Dept Gen Surg,Mol Biol Res Lab, Los Angeles, CA 90095 USA. RP Roesler, JM (reprint author), Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Div Head & Neck Surg,Mol Biol Res Lab, Los Angeles, CA 90095 USA. NR 27 TC 8 Z9 13 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 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUN PY 1998 VL 77 IS 1 BP 50 EP 54 DI 10.1006/jsre.1998.5337 PG 5 WC Surgery SC Surgery GA 108LH UT WOS:000075267500010 PM 9698532 ER PT J AU Nickman, SL AF Nickman, SL TI The spirit of open adoption. SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Child Psychiat Clin, Adopt & Custody Unit, Boston, MA 02114 USA. RP Nickman, SL (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1998 VL 37 IS 6 BP 676 EP 678 DI 10.1097/00004583-199806000-00022 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZR457 UT WOS:000073978700023 ER PT J AU Drake, L Babel, D Stewart, DM Rich, P Ling, MR Breneman, D Scher, RK Martin, AG Pariser, DM Pariser, RJ Ellis, CN Kang, SW Katz, HI McDonald, CJ Muglia, J Savin, RC Webster, G Elewski, BE Leyden, JJ Bucko, AD Tschen, EH Hanifin, JM Morman, MR Shupack, JL Levine, N Lowe, NJ Bergfeld, WF Camisa, C Feingold, DS Konnikov, N Odom, RB Aly, R Greer, DL AF Drake, L Babel, D Stewart, DM Rich, P Ling, MR Breneman, D Scher, RK Martin, AG Pariser, DM Pariser, RJ Ellis, CN Kang, SW Katz, HI McDonald, CJ Muglia, J Savin, RC Webster, G Elewski, BE Leyden, JJ Bucko, AD Tschen, EH Hanifin, JM Morman, MR Shupack, JL Levine, N Lowe, NJ Bergfeld, WF Camisa, C Feingold, DS Konnikov, N Odom, RB Aly, R Greer, DL TI Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID EFFICACY; AGENTS AB Background: Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of fungal infections. Objective: The purpose of this study was to assess the safety and efficacy of oral fluconazole 150, 300, and 450 mg administered once weekly compared with placebo in the treatment of distal subungual onychomycosis of the fingernail caused by dermatophytes. Methods: This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 349 patients with onychomycosis of the fingernails. Clinical and mycologic efficacy as well as measures of safety were assessed monthly for a maximum of 9 months of treatment, with additional safety visits occurring at weeks 2 and 6. For inclusion, patients were required to have clinically and mycologically documented onychomycosis of the fingernail caused by dermatophytes with at least 25% involvement of the target fingernail. After end of therapy, patients with improved or cured fingernails entered a blinded 6-month follow-up without drug treatment during which efficacy was assessed every 2 months. Efficacy was assessed by clinical (visual) and mycologic (microscopic and culture) measures. Clinical measures included assessments of the percentage of target nail involvement, measurement of the distance from the nail fold to the proximal onychomycotic border, and signs and symptoms of onychomycosis. Results: Fluconazole was significantly superior to placebo in eradicating clinical and mycologic symptoms of onychomycosis, both at the end of active treatment and at 6 months after treatment (p = 0.0001 for all efficacy measures). At the end of therapy, 91% to 100% of patients in the fluconazole groups were judged clinical successes, defined as reduction of the affected area of the target nail to less than 25% or cure, compared with 8% for placebo. Clinical cure rates at end of therapy were 76%, 85%, and 90% for fluconazole 150, 300, and 450 mg, respectively, compared with 3% for placebo. These clinical success and cure rates were largely maintained or improved during follow-up. Clinical relapse in cured patients during the follow-up period was very low (1.5% to 3.3%). Fluconazole demonstrated mycologic eradication rates of 89% to 100% at the end of treatment and 90% to 99% at the end of follow-up; for placebo the rates were 8% and 12%, respectively. Conclusion: Fluconazole administered once weekly is safe and effective in eradicating distal subungual onychomycosis of the fingernail caused by dermatophytes. C1 Massachusetts Gen Hosp, Dermatol Clin Invest Unit, Boston, MA 02114 USA. RP Drake, L (reprint author), Massachusetts Gen Hosp, Dermatol Clin Invest Unit, 40 Blossom St, Boston, MA 02114 USA. NR 18 TC 21 Z9 23 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUN PY 1998 VL 38 IS 6 SU S BP S87 EP S94 DI 10.1016/S0190-9622(98)70491-8 PN 2 PG 8 WC Dermatology SC Dermatology GA ZU675 UT WOS:000074221900003 PM 9631990 ER PT J AU Simon, JA Hudes, ES AF Simon, JA Hudes, ES TI Relation of serum ascorbic acid to serum lipids and lipoproteins in US adults SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE ascorbic acid; cholesterol; lipids; vitamin C ID ISCHEMIC-HEART-DISEASE; VITAMIN-E CONSUMPTION; GUINEA-PIGS; ELDERLY POPULATION; HDL-CHOLESTEROL; PLASMA-LIPIDS; METABOLISM; RISK; WOMEN; DEFICIENCY AB Objective: To examine the relation of serum ascorbic acid level to serum lipid and lipoprotein levels among a random sample of the US adult population. Methods: Using linear regression, the relation of serum ascorbic acid level to serum lipid and lipoprotein levels was examined among 5,412 women and 5,116 men enrolled in the Second National Health and Nutrition Examination Survey (NHANES II), 1976-1980. Age, race, body mass index, level of physical activity, level of education, alcohol intake, and dietary energy, cholesterol, and fat intakes, and other potential confounders were included in the multivariate models. Results: Serum ascorbic acid level was independently associated with high-density lipoprotein cholesterol (HDL-C) among women; each 1 mg/dl increase in serum ascorbic acid level (range 0.1 to 2.7 mg/dl) was associated with a 2 mg/dl increase in HDL-C level (p=0.001). Because other investigators have demonstrated an inverse relation between ascorbic acid intake or blood levels and total serum cholesterol in individuals with elevated total serum cholesterol levels, we analyzed four subgroups of NHANES II participants with total serum cholesterol levels >200 mg/dl. Among women with total serum cholesterol levels greater than or equal to 200 mg/dl, each 1 mg/dl increase in serum ascorbic acid level was independently associated with an increase of 2 to 3 mg/dl in HDL-C level (p less than or equal to 0.05). Serum ascorbic acid level was not significantly associated with other serum lipids or lipoproteins. Conclusions: If the observed associations are linked causally, they would suggest that ascorbic acid is a factor in cholesterol homeostasis among women and may be particularly important for women at increased risk for coronary heart disease. C1 San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, Med Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Simon, JA (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, Med Serv, 4150 Clement St, San Francisco, CA 94121 USA. FU NHLBI NIH HHS [HL53479] NR 52 TC 14 Z9 14 U1 0 U2 0 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD JUN PY 1998 VL 17 IS 3 BP 250 EP 255 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZT512 UT WOS:000074095300008 PM 9627911 ER PT J AU Stuart-Tilley, AK Shmukler, BE Brown, D Alper, SL AF Stuart-Tilley, AK Shmukler, BE Brown, D Alper, SL TI Immunolocalization and tissue-specific splicing of AE2 anion exchanger in mouse kidney SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID INTERCALATED CELLS; CL-/HCO3 EXCHANGER; CULTURED-CELLS; MESSENGER-RNAS; CDNA; IDENTIFICATION; TRANSLATION; PROTEINS; CLONING; BAND-3 AB In this study, an epitope-unmasking technique was used to immunolocalize AE2 anion exchanger polypeptide to basolateral plasma membranes of tubular epithelial cells in mouse kidney. Kidney AE2 immunostaining in mouse kidney was less prominent than in rat, consistent with the relative levels of AE2 mRNA and polypeptide in these two species. Glomeruli showed faint but consistent AE2 immunostaining, whereas proximal tubules were generally unstained. Macula densa epithelial cells displayed bright AE2 immunostaining, and cortical thick limbs were stained at a lower intensity. AE2 immunostaining was weak or absent in type B intercalated cells and principal cells of the cortical collecting duct, but increased in intensity in principal cells of the inner stripe of the outer medulla. AE2 staining in medullary thick Limbs was also of greater intensity than in cortical thick limbs. AE2 staining was strong and uniform in the epithelial cells of the inner medullary collecting duct, and in epithelial cells of the papillary surface, the ureter, and the urinary bladder. Extratubular and epithelial cells of the inner medulla also showed punctate intracellular AE2 staining in a Golgi-like distribution that: in contrast to cell surface staining, was sodium dodecyl sulfate-sensitive. Golgi localization of AE2 epitope was confirmed by immunoperoxidase electron microscopy. Reverse transcription-PCR analysis of mouse kidney RNA detected AE2a, AE2b, and an AE2c2 transcript, but an AE2c1 transcript was absent. Unlike in rat, the mouse AE2c2 mRNA splice variant encoded a polypeptide with a novel predicted N-terminal amino acid sequence. C1 Beth Israel Deaconess Med Ctr, Mol Med Unit RW763, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Renal Unit, Boston, MA 02215 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Alper, SL (reprint author), Beth Israel Deaconess Med Ctr, Mol Med Unit RW763, 330 Brookline Ave, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK42956, DK34854, DK43495] NR 35 TC 48 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 1998 VL 9 IS 6 BP 946 EP 959 PG 14 WC Urology & Nephrology SC Urology & Nephrology GA ZQ957 UT WOS:000073920200002 PM 9621277 ER PT J AU Blumenthal, D Thier, SO AF Blumenthal, D Thier, SO TI Leveling the playing field: A report of the Commonwealth Fund Task Force on academic health centers SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article; Proceedings Paper CT Academy Sesquicentennial Symposium on Toward an Urban Health Agenda CY NOV 17-18, 1997 CL NEW YORK ACAD MED, NEW YORK, NEW YORK SP New York Acad Med HO NEW YORK ACAD MED ID INDUSTRY C1 Partners HealthCare Syst Inc, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Commonwealth Fund, Task Force Acad Hlth Ctr, New York, NY USA. RP Blumenthal, D (reprint author), Hlth Policy Res & Dev Unit, 50 Staniford St, Boston, MA 02114 USA. NR 18 TC 1 Z9 1 U1 3 U2 3 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 JUN PY 1998 VL 75 IS 2 BP 330 EP 346 DI 10.1007/BF02345101 PG 17 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 104ZJ UT WOS:000075046900017 PM 9684245 ER PT J AU Koenig, F McGovern, FJ Enquist, H Larne, R Deutsch, TF Schomacker, KT AF Koenig, F McGovern, FJ Enquist, H Larne, R Deutsch, TF Schomacker, KT TI Autofluorescence guided biopsy for the early diagnosis of bladder carcinoma SO JOURNAL OF UROLOGY LA English DT Article DE carcinoma; bladder; fluorescence; diagnosis; lasers ID FLUORESCENCE; CANCER AB Purpose: We validate the usefulness of laser-induced autofluorescence for the detection of bladder carcinoma. Materials and Methods: We obtained and analyzed fluorescence spectra from 75 patients in whom bladder cancer was suspected. Tissue fluorescence was excited by a nitrogen laser using a quartz optical fiber placed in gentle contact with the area of interest. The laser-induced autofluorescence spectrum was recorded using an intensified optical multichannel analyzer system. Spectra were corrected for the spectral response of the optical system, and the ratios of laser-induced autofluorescence intensities (I) at 385 and 455 nm. (I-385/I-455) were determined. We had previously established this ratio as a diagnostic algorithm. We included only suspicious bladder lesions (erythematous, edematous, raised and so forth) that were difficult to diagnose by cystoscopy as well as areas from which random biopsies were obtained. The fluorescence ratio algorithm was applied to 130 bladder areas. Results: Of the 130 biopsies obtained during routine cystoscopy 107 (82%) were nonmalignant by histological classification. In contrast, because laser-induced autofluorescence effectively guides biopsies towards malignant lesions, only 30 biopsies (72% fewer) would have been obtained from nonmalignant tissue if the fluorescence ratio that identifies 95% of malignant lesions (95th percentile) had been selected as the decision criterion during standard cystoscopy. Conclusions: By guiding the surgeon to suspicious lesions that are most likely to be malignant, laser-induced autofluorescence substantially decreases the number of biopsies obtained from nonmalignant tissue during cystoscopy to diagnose bladder carcinoma. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Koenig, F (reprint author), Humboldt Univ, Charite Med Sch, Dept Urol, Schumannstr 20-21, D-10117 Berlin, Germany. NR 10 TC 43 Z9 48 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1998 VL 159 IS 6 BP 1871 EP 1875 DI 10.1016/S0022-5347(01)63183-5 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA ZM868 UT WOS:000073584400025 PM 9598478 ER PT J AU Wasson, JH Fowler, FJ Barry, MJ AF Wasson, JH Fowler, FJ Barry, MJ TI Androgen deprivation therapy for asymptomatic advanced prostate cancer in the prostate specific antigen era: A national survey of urologist beliefs and practices SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; androgens; physician's practice patterns; urology ID ENDOCRINE THERAPY; CARCINOMA AB Purpose: The use of androgen deprivation for prostate cancer without symptomatic metastases to the skeleton is controversial. However, by 1995 the use of medical androgen deprivation by injection was the thirteenth largest category of physician reimbursement by Medicare. To what degree do urologist attitudes towards androgen deprivation account for this growth? Materials and Methods: A survey was mailed to 582 United States urologists practicing at least 20 hours per week in 1995 which asked about use of androgen deprivation therapy when prostate specific antigen (PSA) levels rise after primary therapy (surgery or radiation). They were also asked whether they believed androgen deprivation provided a survival benefit for patients with asymptomatic stages C and D disease. Results: The response rate was 68%. Of the respondents 68% reported that they recommend androgen deprivation at least half of the time for men whose PSA is newly or persistently elevated following radical prostatectomy. Most (81%) urologists who believe that androgen deprivation offers a survival benefit for stage C disease said they prescribed it but more than half (53%) who do not believe in the efficacy of this treatment also said they still prescribe it. Conclusions: Many urologists maintain an inclination to prescribe androgen deprivation for a rising or elevated PSA despite the absence of information about the benefit of this approach and their own conflicting beliefs. C1 Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Dartmouth Med Sch, Hanover, NH 03756 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Wasson, JH (reprint author), Dartmouth Med Sch, Hanover, NH 03756 USA. FU AHRQ HHS [HS 08397] NR 22 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1998 VL 159 IS 6 BP 1993 EP 1996 DI 10.1016/S0022-5347(01)63223-3 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA ZM868 UT WOS:000073584400065 PM 9598505 ER PT J AU Fallat, ME Siow, Y Klar, EA Belker, AM Maclaughlin, DT AF Fallat, ME Siow, Y Klar, EA Belker, AM Maclaughlin, DT TI The presence of Mullerian inhibiting substance binding sites in human sperm SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the American-Society-of-Andrology CY MAR 31-APR 04, 1995 CL RALEIGH, NORTH CAROLINA SP Amer Soc Androl DE MIS binding; sperm ID TYROSINE KINASE-ACTIVITY; EPIDERMAL GROWTH-FACTOR; ACROSOME REACTION; GRANULOSA-CELLS; FACTOR-BETA; RECEPTOR; FETAL; EXPRESSION; HORMONE; PHOSPHORYLATION AB Purpose: The binding of Mullerian inhibiting substance (MIS) to human sperm was investigated using immunohistological techniques. Materials and Methods: Sperm from 5 normal donors and 6 subfertile men were studied. Whole or thin-sectioned sperm were incubated without or with recombinant human MIS (0.5 mu g./ml.). MIS binding was identified under light microscopy (LM) using rabbit anti-human MIS antibodies tagged with goat IgG-horseradish peroxidase and diaminobenzidine as substrate, or by scanning and transmission electron microscopy (SEM and TEM) using gold labeled goat IgG. Intracellular MIS binding in sperm sections was examined by TEM. Antibodies were omitted in the controls. Results: Under LM, DAB staining was present on sperm incubated with or without MIS and absent on controls. Using SEM, gold particles were found primarily on the surfaces of the sperm head with less binding to the tail. With TEM, the clustering of gold particles around the head of sperm represents MIS binding, but very few or no gold particles could be found associated with the sperm tail. MIS binding was also found associated with intracellular structures, but only within the head of the sperm. Overall, less gold particle binding was present in subfertile compared with normal sperm. Conclusions: These results suggest that MIS is bound to the sperm surface and sperm from normally fertile men have increased MIS binding. The function of MIS in sperm is unknown, but the presence of MIS binding suggests a direct role(s) in sperm function. C1 Univ Louisville, Dept Surg, Louisville, KY 40292 USA. Jewish Hosp, Louisville, KY USA. Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Fallat, ME (reprint author), Kosair Childrens Hosp, POB 35070, Louisville, KY 40232 USA. NR 37 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1998 VL 159 IS 6 BP 2210 EP 2214 DI 10.1016/S0022-5347(01)63307-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA ZM868 UT WOS:000073584400149 PM 9598571 ER PT J AU Hampel, OZ Kattan, MW Yang, G Haidacher, SJ Saleh, GY Thompson, TC Wheeler, TM Marcelli, M AF Hampel, OZ Kattan, MW Yang, G Haidacher, SJ Saleh, GY Thompson, TC Wheeler, TM Marcelli, M TI Quantitative immunohistochemical analysis of insulin-like growth factor binding protein-3 in human prostatic adenocarcinoma: A prognostic study SO JOURNAL OF UROLOGY LA English DT Article DE IGFBP-3; prostate adenocarcinoma; cancer biology; IGF axis; immunocytochemistry ID BREAST-CANCER CELLS; FACTOR IGF; CATHEPSIN-D; MESSENGER-RNA; I RECEPTOR; CARCINOMA; BENIGN; EXPRESSION; TISSUE; LOCALIZATION AB Purpose: We sought to characterize and quantitate the expression of IGFBP-3 in adenocarcinoma of the prostate and to test whether it correlated with tumor differentiation determined by Gleason grade. We also investigated the potential of using IGFBP-3 as a prognostic indicator of clinically localized prostate cancer. Materials and Methods: Initially we evaluated the expression of IGFBP-3 in six normal and twenty neoplastic prostates using standard immunohistochemical techniques (study 1). We then obtained radical prostatectomy specimens from twenty-four patients with a preoperative diagnosis of clinically localized prostate adenocarcinoma and five year follow up information, and nine normal prostates from organ donors or from patients undergoing cystoprostatectomy (study 2). All specimens were immunostained with a polyclonal anti-human IGFBP-3 antibody. A single pathologist reviewed all sections and assigned a Gleason grade to each cancer focus. Using computer-assisted video image analysis, we quantified the intensity of IGFBP-3 immunostaining of each cancer focus and of normal controls. Results: Normal prostatic epithelium showed intense cytoplasmic IGFBP-3 staining. The stromal compartment showed less intense staining, although there were occasional areas with strong immunoreactivity. The cellular distribution of IGFBP-3 staining in prostatic adenocarcinoma was comparable to normal tissue; however, the intensity of detectable staining in neoplastic epithelial cells was significantly decreased. Two foci of prostatic intraepithelial neoplasia (PIN) demonstrated IGFBP-3 immunoreactivity decreased in comparison to normal epithelium, but greater than prostatic adenocarcinoma. Histologically normal epithelium surrounding cancer foci also showed decreased immunostaining for IGFBP-3 compared with normal prostate. The marked decrease in immunostaining intensity of IGFBP-3 in prostate adenocarcinoma was not associated with Gleason grade or with clinical outcome. Conclusion: Malignant transformation of prostatic epithelium was associated with a significant decrease in the amount of immunoreactive IGFBP-3 (p < 0.0001); however, this parameter did not correlate with Gleason grade of the tumor or with patient outcome. The decrease in immunostaining intensity of IGFBP-3 in all Gleason grades and in PIN suggests that lower expression of IGFBP-3 is an early event in prostatic carcinogenesis. The finding that decreased IGFBP-3 immunostaining did not correlate with clinical outcome suggests that this parameter is not a therapy-guiding prognostic indicator for clinically localized prostate cancer. C1 Baylor Coll Med, VA Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Scott Dept Urol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Informat Technol Program, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. RP Marcelli, M (reprint author), Baylor Coll Med, VA Med Ctr, Dept Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 48 TC 34 Z9 35 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1998 VL 159 IS 6 BP 2220 EP 2225 DI 10.1016/S0022-5347(01)63309-3 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA ZM868 UT WOS:000073584400151 PM 9598573 ER PT J AU Brewster, DC Geller, SC Kaufman, JA Cambria, RP Gertler, JP LaMuraglia, GM Atamian, S Abbott, WM AF Brewster, DC Geller, SC Kaufman, JA Cambria, RP Gertler, JP LaMuraglia, GM Atamian, S Abbott, WM TI Initial experience with endovascular aneurysm repair: Comparison of early results with outcome of conventional open repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the New England Society-for-Vascular-Surgery CY SEP 18-19, 1997 CL BOLTON LANDING, NEW YORK SP New England Soc Vasc Surg ID ABDOMINAL AORTIC-ANEURYSM; ENDOLUMINAL REPAIR; GRAFT PLACEMENT; EXCLUSION; MANAGEMENT; LESIONS AB Purpose: To determine the safety, effectiveness, and problems encountered with endovascular repair of abdominal aortic aneurysm (AAA). Initial experience with endoluminal stent grafts was examined and compared With outcome for a matched concurrent control group undergoing conventional operative repair of AAA. Methods: Over a a-year period, 30 patients underwent attempts at endovascular repair of infrarenal AAA. Of the 28 (93%) successfully implanted endografts, 8 were tube endografts, 8 bifurcated grafts, and 12 aortouniiliac grafts combined with femorofemoral bypass. Most of the procedures were performed in the past year because the availability of bifurcated and aortoiliac endografts markedly expanded the percentage of patients with AAA who might be treated with endoluminal methods. The follow-up period ranged from 1 to 44 months, with a mean value of 11 months. Results: Endovascular procedures demonstrated significant advantages with respect to reduced blood loss (408 versus 1287 ml), use of an intensive care unit (0.1 versus 1.75 days), length of hospitalization (3.9 versus 10.3 days), and quicker recovery (11 versus 47 days). Although the total number of postoperative complications was identical for the two groups, the nature of the complications differed considerably. Local and vascular complications characteristic of endovascular repair could frequently be corrected at the time of the procedure and tended to be less severe than systemic or remote complications, which predominated among the open surgical repair group. On an intent-to-treat basis, 23 (77%) of the 30 AAAs were successfully managed with endoluminal repair. The seven (23%) failures were attributable to two immediate conversions caused by access problems, three persistent endoleaks, one late conversion caused by AAA expansion, and one late rupture. Conclusions: Although less definitive than those for conventional operations, these early results suggest that endovascular AAA repair offers considerable benefits for appropriate patients. The results justify continued application of this method of AAA repair, particularly in the treatment of older persons at high risk. C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Sect Vasc Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Brewster, DC (reprint author), 1 Hawthorne Pl, Boston, MA 02114 USA. NR 46 TC 197 Z9 201 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 1998 VL 27 IS 6 BP 992 EP 1003 DI 10.1016/S0741-5214(98)70002-3 PG 12 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA ZV729 UT WOS:000074335200002 PM 9652461 ER PT J AU Wirthlin, DJ Buradagunta, S Edwards, RA Brewster, DC Cambria, RP Gertler, JP LaMuraglia, GM Jordan, DE Kvedar, JC Abbott, WM AF Wirthlin, DJ Buradagunta, S Edwards, RA Brewster, DC Cambria, RP Gertler, JP LaMuraglia, GM Jordan, DE Kvedar, JC Abbott, WM TI Telemedicine in vascular surgery: Feasibility of digital imaging for remote management of wounds SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the New England Society-for-Vascular-Surgery CY SEP 18-19, 1997 CL BOLTON LANDING, NEW YORK SP New England Soc Vasc Surg ID CLINICAL DECISION-MAKING; SAPHENOUS-VEIN; BYPASS; COMPLICATIONS; VARIABILITY AB Purpose: Telemedicine coupled with digital photography could potentially improve the quality of outpatient wound care and decrease medical cost by allowing home care nurses to electronically transmit images of patients' wounds to treating surgeons. To determine the feasibility of this technology, we compared bedside wound examination by onsite surgeons with viewing digital images of wounds by remote surgeons. Methods: Over 6 weeks, 38 wounds in 24 inpatients were photographed with a Kodak DC50 digital camera (resolution 756 x 504 pixels/in(2)). Agreements regarding wound description (edema, erythema, cellulitis, necrosis, gangrene, ischemia, and granulation) and wound management (presence of healing problems, need for emergent evaluation, need for antibiotics, and need for hospitalization) were calculated among onsite surgeons and between onsite and remote surgeons. Sensitivity and specificity of remote wound diagnosis compared with bedside examination were calculated. Potential correlates of agreement, level of surgical training, certainty of diagnosis, and wound type were evaluated by multivariate analysis. Results: Agreement between onsite and remote surgeons (66% to 95% for wound description and 64% to 95% for wound management) matched agreement among onsite surgeons (64% to 85% for wound description and 63% to 91% for wound management). Moreover, when onsite agreement was low (i.e., 64% for erythema) agreement between onsite and remote surgeons was similarly low (i.e., 66% for erythema). Sensitivity of remote diagnosis ranged from 78% (gangrene) to 98% (presence of wound healing problem), whereas specificity ranged from 27% (erythema) to 100% (ischemia). Agreement was influenced by wound type (p < 0.01) but not by certainty of diagnosis (p > 0.01) or level of surgical training (p > 0.01). Conclusions Wound evaluation on the basis of viewing digital images is comparable with standard wound examination and renders similar diagnoses and treatment in the majority of cases. Digital imaging for remote wound management is feasible and holds significant promise for improving outpatient vascular wound care. C1 Massachusetts Gen Hosp, Dept Surg, Div Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners Telemed Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wirthlin, DJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Vasc Surg, WAC 458, Boston, MA 02114 USA. RI Edwards, Roger/C-9736-2010 NR 33 TC 70 Z9 71 U1 2 U2 5 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUN PY 1998 VL 27 IS 6 BP 1089 EP 1099 DI 10.1016/S0741-5214(98)70011-4 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA ZV729 UT WOS:000074335200022 PM 9652471 ER PT J AU Sullivan, N Sun, Y Sattentau, Q Thali, M Wu, D Denisova, G Gershoni, J Robinson, J Moore, J Sodroski, J AF Sullivan, N Sun, Y Sattentau, Q Thali, M Wu, D Denisova, G Gershoni, J Robinson, J Moore, J Sodroski, J TI CD4-induced conformational changes in the human immunodeficiency virus type 1 gp120 glycoprotein: Consequences for virus entry and neutralization SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; SOLUBLE CD4 BINDING; EXTERIOR ENVELOPE GLYCOPROTEIN; RECEPTOR-MEDIATED ACTIVATION; MEMBRANE-FUSION; SYNCYTIUM FORMATION; HIV-1 GP120; INFLUENZA HEMAGGLUTININ; EPITOPE EXPOSURE; SYNDROME AIDS AB Human immunodeficiency virus type 1 (HIV-1) entry into target cells involves sequential binding of the gp120 exterior envelope glycoprotein to CD4 and to specific chemokine receptors. Soluble CD4 (sCD4) is thought to mimic membrane-anchored CD4, and its binding alters the conformation of the HIV-1 envelope glycoproteins. Two cross-competing monoclonal antibodies, 17b and CG10, that recognize CD4-inducible gp120 epitopes and that block gp120-chemokine receptor binding were used to investigate the nature and functional significance of gp120 conformational changes initiated by CD4 binding. Envelope glycoproteins derived from both T-cell line-adapted and primary HIV-1 isolates exhibited increased binding of the 17b antibody in the presence of sCD4. CD4-induced exposure of the 17b epitope on the oligomeric envelope glcoprotein complex occurred over a wide range of temperatures and involved movement of the gp120 V1/V2 variable loops. Amino acid changes that reduced the efficiency of 17b epitope exposure following CD4 binding invariably compromised the ability of the HIV-1 envelope glycoproteins to form syncytia or to support virus entry. Comparison of the CD4 dependence and neutralization efficiencies of the 17b and CG10 antibodies suggested that the epitopes for these antibodies are minimally accessible following attachment of gp120 to cell surface CD4. These results underscore the functional importance of these CD-l-induced changes in gp120 conformation and illustrate viral strategies for sequestering chemokine receptor-binding regions from the humoral immune response. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Pathol,Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Ctr Immunol, F-13288 Marseille, France. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Cell Res & Immunol, IL-69978 Tel Aviv, Israel. Tulane Univ, Sch Med, Dept Pediat, New Orleans, LA 70112 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. RP Sodroski, J (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Pathol,Div Human Retrovirol, JFB824,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R37 AI024755, AI 39420, AI 36082, R01 AI039420, R37 AI036082, R01 AI031783, AI 24755] NR 74 TC 244 Z9 247 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1998 VL 72 IS 6 BP 4694 EP 4703 PG 10 WC Virology SC Virology GA ZM029 UT WOS:000073497600017 PM 9573233 ER PT J AU Carnes, M McMurray, J Allen, C Foster, S Middleton, WS AF Carnes, M McMurray, J Allen, C Foster, S Middleton, WS TI Development of a women's health fellowship. SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 Univ Wisconsin, Madison, WI 53705 USA. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1059-7115 J9 J WOMENS HEALTH JI J. Womens Health PD JUN PY 1998 VL 7 IS 5 BP 630 EP 630 PG 1 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 ZW759 UT WOS:000074445500066 ER PT J AU Herak-Kramberger, CM Brown, D Sabolic, I AF Herak-Kramberger, CM Brown, D Sabolic, I TI Cadmium inhibits vacuolar H+-ATPase and endocytosis in rat kidney cortex SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Conference on Forefronts in Nephrology - Genes and Genetics in Hypertension and Vascular Disease CY SEP 04-07, 1997 CL GROSS DOLLN, GERMANY DE proximal tubule; brush border; endocytosis; adenosine triphosphatase; vacuolar H+-ATPase; cadmium nephropathy; nephrotoxicity ID BORDER MEMBRANE-VESICLES; PROXIMAL CONVOLUTED TUBULES; INTOXICATED RATS; METALLOTHIONEIN CDMT; CULTURED-CELLS; TREATED RATS; TRANSPORT; DEGRADATION; ENDOSOMES; CHLORIDE AB The mechanism of cadmium (Cd)-induced damage in the mammalian proximal tubule that is manifested by defects in reabsorption of various compounds, is poorly understood. A vacuolar H+-ATPase (V-ATPase) in proximal tubule (PT) brush border and intracellular vesicles may be affected by Cd, and this may influence intracellular vesicle trafficking and reabsorption of the filtered proteins. We studied the effects of Cd on V-ATPase and endocytosis in rat renal PT in vivo and on acidification mechanisms in isolated renal cortical organelles in vitro. The V-ATPase activity in brush border membrane (BBM) from Cd-intoxicated rats was 40% lower compared to that in control animals. Immunofluorescence studies in cortical tissue sections and Western blot studies in BBM from Cd-treated rats showed a strongly decreased abundance of the 31 kDa and 70 kDa V-ATPase subunits. Functional studies in vivo showed a dramatically diminished endocytosis of fluorescein-labeled dextran in PT cells from Cd-treated animals, whereas morphological studies revealed a loss of endocytic invaginations and subapical vesicles in the same cells. In studies in vitro, Cd inhibited V-ATPase activity in a concentration-and time-dependent manner in both BBM and endocytic vesicles, whereas in endocytic vesicles, Cd inhibited ATP-driven intravesicular acidification and accelerated the dissipation of transmembrane pH gradients. We conclude that Cd may impair acidification in cell organelles by (a) causing a loss of V-ATPase protein in their limiting membranes, (b) inhibiting the intrinsic V-ATPase activity, and (c) dissipating the transmembrane pH gradient. This may inhibit endocytosis of filtered proteins and impair vesicle-mediated recycling of some membrane transporters, thus contributing to the loss of reabsorptive capacity of the PT. C1 Inst Med Res & Occupat Hlth, Zagreb 10001, Croatia. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sabolic, I (reprint author), Inst Med Res & Occupat Hlth, Ksaverska Cesta 2,POB 291, Zagreb 10001, Croatia. EM sabolic@imi.hr FU FIC NIH HHS [1-R03-TW00512-A-01-A1]; PHS HHS [DW 42956] NR 48 TC 47 Z9 48 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1998 VL 53 IS 6 BP 1713 EP 1726 DI 10.1046/j.1523-1755.1998.00914.x PG 14 WC Urology & Nephrology SC Urology & Nephrology GA ZN892 UT WOS:000073694000035 PM 9607204 ER PT J AU Stone, M AF Stone, M TI Panic free: Eliminate anxiety/panic attacks without drugs and take control of your life. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, M (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JUN 1 PY 1998 VL 123 IS 10 BP 134 EP 134 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA ZR997 UT WOS:000074037300137 ER PT J AU Stone, M AF Stone, M TI Overcoming panic disorder: A woman's guide. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, M (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD JUN 1 PY 1998 VL 123 IS 10 BP 134 EP 134 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA ZR997 UT WOS:000074037300138 ER PT J AU Balin, BJ Gerard, HC Arking, EJ Appelt, DM Branigan, PJ Abrams, JT Whittum-Hudson, JA Hudson, AP AF Balin, BJ Gerard, HC Arking, EJ Appelt, DM Branigan, PJ Abrams, JT Whittum-Hudson, JA Hudson, AP TI Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain SO MEDICAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Chlamydia; Alzheimer's disease; inflammation; dementia; infection ID FIBRILLARY ACIDIC PROTEIN; POLYMERASE CHAIN-REACTION; PAIRED HELICAL FILAMENTS; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; HERPES-SIMPLEX VIRUS; APOLIPOPROTEIN-E; STRAIN TWAR; CARDIOVASCULAR-DISEASE; REITERS-SYNDROME AB We assessed whether the intracellular bacterium Chlamydia pneumoniae was present in post-mortem brain samples from patients with and without late-onset Alzheimer's disease (AD), since some indirect evidence seems to suggest that infection with the organism might be associated with the disease. Nucleic acids prepared from those samples were screened by polymerase chain reaction (PCR) assay for DNA sequences from the bacterium, and such analyses showed that brain areas with typical AD-related neuropathology were positive for the organism in 17/19 AD patients. Similar analyses of identical brain areas of 18/19 control patients were PCR-negative. Electron- and immunoelectron-microscopic studies of tissues from affected AD brain regions identified chlamydial elementary and reticulate bodies, but similar examinations of non-AD brains were negative for the bacterium. Culture studies of a subset of affected AD brain tissues for C. pneumoniae were strongly positive, while identically performed analyses of non-AD brain tissues were negative. Reverse transcription (RT)-PCR assays using RNA from affected areas of AD brains confirmed that transcripts from two important C. pneumoniae genes were present in those samples but not in controls. Immunohistochemical examination of AD brains, but not those of controls, identified C. pneumoniae within pericytes, microglia, and astroglia. Further immunolabelling studies confirmed the organisms' intracellular presence primarily in areas of neuropathology in the AD brain, Thus, C. pneumoniae is present, viable, and transcriptionally active in areas of neuropathology in the AD brain, possibly suggesting that infection with the organism is a risk factor for late-onset AD. C1 Allegheny Univ Hlth Sci, Dept Pathol & Lab Med, MCP Hahnemann Sch Med, Philadelphia, PA 19102 USA. Allegheny Univ Hlth Sci, Dept Microbiol & Immunol, MCP Hahnemann Sch Med, Philadelphia, PA 19129 USA. Vet Affairs Med Ctr, Dept Med Res, Philadelphia, PA 19104 USA. Allegheny Univ Hlth Sci, Dept Dermatol, MCP Hahnemann Sch Med, Philadelphia, PA 19102 USA. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Ocular Immunol Labs, Baltimore, MD 21287 USA. RP Hudson, AP (reprint author), Wayne State Univ, Sch Med, Dept Immunol & Microbiol, Gordon H Scott Hall,540 E Canfield Ave, Detroit, MI 48201 USA. EM ahudson@med.wayne.edu FU NEI NIH HHS [EY-03324]; NIA NIH HHS [AG-10160]; NIAMS NIH HHS [AR-42541] NR 97 TC 236 Z9 245 U1 0 U2 8 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0300-8584 J9 MED MICROBIOL IMMUN JI Med. Microbiol. Immunol. PD JUN PY 1998 VL 187 IS 1 BP 23 EP 42 DI 10.1007/s004300050071 PG 20 WC Immunology; Microbiology SC Immunology; Microbiology GA 114KQ UT WOS:000075608700005 PM 9749980 ER PT J AU Restrepo, MI Najvar, LK Fothergill, AW Graybill, JR AF Restrepo, MI Najvar, LK Fothergill, AW Graybill, JR TI Pradimicin therapy of disseminated Candida tropicalis infection in the mouse SO MEDICAL MYCOLOGY LA English DT Article DE BMS; Candida tropicalis; fluconazole; mouse model; pradimicin ID FLUCONAZOLE; ANTIFUNGAL; MICE AB EMS 181184 (BMS), an analogue of pradimicin, was administered intravenously to neutropenic mice infected with either a fluconazole-susceptible or a fluconazole-resistant clinical isolate of Candida tropicalis. EMS prolonged survival at doses >3 mg kg(-1) day(-1), and at higher doses reduced tissue counts in mice. EMS was less potent mg for mg than amphotericin B. Combined EMS and amphotericin B were no more effective than either of the individual drugs. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Div Infect Dis 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI Restrepo, Marcos/H-4442-2014 NR 6 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD JUN PY 1998 VL 36 IS 3 BP 181 EP 184 DI 10.1080/02681219880000271 PG 4 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 105XL UT WOS:000075100600008 PM 9776832 ER PT J AU Jiroutek, MR Chen, MH Johnston, CC Longcope, C AF Jiroutek, MR Chen, MH Johnston, CC Longcope, C TI Changes in reproductive hormones and sex hormone-binding globulin in a group of postmenopausal women measured over 10 years SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article DE hormones; menopause; estrogens; androgens; SHBG; gonadotropins ID POST-MENOPAUSAL WOMEN; BONE MASS; ESTROGEN DYNAMICS; STEROIDS; OVARIAN; ANDROGEN; REPRODUCIBILITY; PERIMENOPAUSAL; PREMENOPAUSAL; PROFILES AB Objective: As part of a study on hormones and bone density in older women, we measured a number of steroid and polypeptide hormones at 4- to 6-month intervals in 32 women over a 10-year period. Design: All women were postmenopausal during this time and all measurements from 12 months after the menopause to the end were used in the analysis. To determine whether there was a significant trend in steroid or polypeptide hormones over the years, the data were analyzed by random coefficient linear regression against number of months since menopause. Results: There was no significant trend in the concentrations of estrone, estrone sulfate, dehydroepiandrosterone, and follicle stimulating hormone. There was a significant decline in the concentrations of estradiol, dihydrotestosterone, dehydroepiandrosterone sulfate, and luteinizing hormone. There was a rise in the levels of androstenedione and testosterone. Conclusions: The changes in the concentration of sex hormone-binding globulin could be fitted to a quadratic equation with an initial rise in the concentration followed by a decline. Thus, the trend in hormone concentrations shows no set pattern with aging in the postmenopausal years. (C) 1998, The North American Menopause Society. C1 Univ Massachusetts, Sch Med, Dept Obstet Gynecol, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Indiana Med Sch, Dept Med, Indianapolis, IN USA. RP Longcope, C (reprint author), Univ Massachusetts, Sch Med, Dept Obstet Gynecol, Worcester, MA 01655 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 29 TC 37 Z9 40 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD SUM PY 1998 VL 5 IS 2 BP 90 EP 94 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ZV440 UT WOS:000074304800006 PM 9689202 ER PT J AU Sepulveda, JL Belaguli, N Nigam, V Chen, CY Nemer, M Schwartz, RJ AF Sepulveda, JL Belaguli, N Nigam, V Chen, CY Nemer, M Schwartz, RJ TI GATA-4 and Nkx-2.5 coactivate Nkx-2 DNA binding targets: Role for regulating early cardiac gene expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SERUM RESPONSE FACTOR; THYROID TRANSCRIPTION FACTOR-1; ZINC-FINGER; HOMEODOMAIN PROTEINS; COOPERATIVE INTERACTION; NEGATIVE REGULATION; DEVELOPING HEART; TINMAN HOMOLOG; CELL LINEAGES; FACTOR FAMILY AB The cardiogenic homeodomain factor Nkx-2.5 and serum response factor (SRF) provide strong transcriptional coactivation of the cardiac alpha-actin (alpha CA) promoter in fibroblasts (C. Y. Chen and R. J. Schwartz, Mol. Cell. Biol. 16:6372-6384, 1996). We demonstrate here that Nkx-2.5 also cooperates with GATA-4, a dual C-4 zinc finger transcription factor expressed in early cardiac progenitor cells, to activate the alpha CA promoter and a minimal promoter, containing only multimerized Nkx-2.5 DNA binding sites (NKEs), in heterologous CV-1 fibroblasts. Transcriptional activity requires the N-terminal activation domain of Nkx-2.5 and Nkx-2.5 binding activity through its homeodomain but does not require GATA-4's activation domain, The minimal interactive regions were mapped to the homeodomain of Nkx-2.5 and the second zinc finger of GATA-4. Removal of Nkx-2.5's C-terminal inhibitory domain stimulated robust transcriptional activity, comparable to the effects of GATA-4 on wild-type Nkx-2.5, which in part facilitated Nkx-2.5 DNA binding activity. We postulate the following simple model: GATA-4 induces a conformational change in Nkx-2.5 that displaces the C-terminal inhibitory domain, thus eliciting transcriptional activation of promoters containing Nkx-2.5 DNA binding targets. Therefore, alpha Ca promoter activity appears to be regulated through the combinatorial interactions of at least three cardiac tissue-enriched transcription factors, Nkx-2.5, GATA-4, and SRF. C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. VA Med Ctr, Houston, TX 77030 USA. Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. Clin Res Inst Montreal, Lab Dev & Differentiat Cardiaques, Montreal, PQ H2W 1R7, Canada. RP Schwartz, RJ (reprint author), Baylor Coll Med, Dept Cell Biol, 1 Baylor Plaza, Houston, TX 77030 USA. FU NHLBI NIH HHS [P01 HL049953, P01 HL49953, R01 HL50422] NR 65 TC 239 Z9 244 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1998 VL 18 IS 6 BP 3405 EP 3415 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZN267 UT WOS:000073628800031 PM 9584181 ER PT J AU Ohh, M Yauch, RL Lonergan, KM Whaley, JM Stemmer-Rachamimov, AO Louis, DN Gavin, BJ Kley, N Kaelin, WG Iliopoulos, O AF Ohh, M Yauch, RL Lonergan, KM Whaley, JM Stemmer-Rachamimov, AO Louis, DN Gavin, BJ Kley, N Kaelin, WG Iliopoulos, O TI The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix SO MOLECULAR CELL LA English DT Article ID POLYCYSTIC KIDNEY-DISEASE; ENDOTHELIAL GROWTH-FACTOR; RENAL-CARCINOMA CELLS; GENE-PRODUCT; VHL GENE; MUTATIONS; ADHESION; INTEGRIN; BINDING; TRANSFORMATION AB Fibronectin coimmunoprecipitated with wild-type von Hippel-Lindau protein (pVHL) but not tumor-derived pVHL mutants. Immunofluorescence and biochemical fractionation experiments showed that fibronectin colocalized with a fraction of pVHL associated with the endoplasmic reticulum, and cold competition experiments suggested that complexes between fibronectin and pVHL exist in intact cells. Assembly of an extracellular fibronectin matrix by VHL-/- renal carcinoma cells, as determined by immunofluorescence and ELISA assays, was grossly defective compared with VHL+/+ renal carcinoma cells. Reintroduction of wildtype, but not mutant, pVHL into VHL-/- renal carcinoma cells partially corrected this defect. Finally, extracellular fibronectin matrix assembly by VHL-/- mouse embryos and mouse embryo fibroblasts (MEFs), unlike their VHL+/+ counterparts, was grossly impaired. These data support a direct role of pVHL in fibronectin matrix assembly. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ 08543 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Genome Therapeut Corp, Waltham, MA 02154 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 53 TC 334 Z9 342 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD JUN PY 1998 VL 1 IS 7 BP 959 EP 968 DI 10.1016/S1097-2765(00)80096-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZW235 UT WOS:000074389200003 PM 9651579 ER PT J AU Scherer, PE Bickel, PE Kotler, M Lodish, HF AF Scherer, PE Bickel, PE Kotler, M Lodish, HF TI Cloning of cell-specific secreted and surface proteins by subtractive antibody screening SO NATURE BIOTECHNOLOGY LA English DT Article DE differential expression; adipocyte ID HIGH-DENSITY-LIPOPROTEIN; MONOCLONAL-ANTIBODIES; EXPRESSION CLONING; 3T3-L1 ADIPOCYTES; AMINE OXIDASE; VI COLLAGEN; GLYCOPROTEIN; SEQUENCE; VIGILIN; RAT AB To identify and clone genes that encode cell-or tissue-specific secreted and surface proteins, a polyclonal antiserum was raised against a complex mixture of surface or secreted proteins from the target cell, followed by immunodepletion of antibodies that recognize proteins from a nontarget cell or tissue. The depleted antiserum is used to screen bacteriophage cDNA expression libraries. Because of our interest in how adipocytes communicate with other cells, we have used this method to clone cDNAs encoding secreted and plasma membrane proteins that are induced during adipocyte differentiation. We describe several of these, including a novel plasma membrane-associated protein, S3-12. C1 Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Lodish, HF (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NIDDK NIH HHS [DK02219, DK47618] NR 47 TC 86 Z9 88 U1 0 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 1998 VL 16 IS 6 BP 581 EP 586 DI 10.1038/nbt0698-581 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA ZR049 UT WOS:000073930600037 PM 9624692 ER PT J AU Kolquist, KA Ellisen, LW Counter, CM Meyerson, M Tan, LK Weinberg, RA Haber, DA Gerald, WL AF Kolquist, KA Ellisen, LW Counter, CM Meyerson, M Tan, LK Weinberg, RA Haber, DA Gerald, WL TI Expression of TERT in early premalignant lesions and a subset of cells in normal tissues SO NATURE GENETICS LA English DT Article ID TELOMERASE ACTIVITY; HUMAN BREAST; CANCER; RNA AB Activation of telomerase, the enzyme that synthesizes the telomere ends of linear chromosomes, has been implicated in human cell immortalization and cancer cell pathogenesis. Enzyme activity is undetectable in most normal cells and tissues, but present in immortal cells and cancer tissues(1-3). While expression of TERC, the RNA component of telomerase, is widespread(4-6), the restricted expression pattern of TERT, the telomerase catalytic subunit gene, is correlated with telomerase activity(7-9), and its ectopic expression in telomerase-negative cells is sufficient to reconstitute telomerase activity(10-12) and extend cellular lifespan(13). We have used in situ hybridization to study TERT expression at the single-cell level in normal tissues and in various stages of tumour progression. In normal tissues, including some that are known to be telomerase-negative, TERT mRNA was present in specific subsets of cells thought to have long-term proliferative capacity. This included mitotically inactive breast lobular epithelium in addition to some actively regenerating cells such as the stratum basale of the skin. TERT expression appeared early during tumorigenesis in vivo, beginning with early pre-invasive changes in human breast and colon tissues and increasing mRNA present within individual cells and in the number of expressing cells within a neoplastic lesion. The physiological expression of TERT within normal epithelial cells that retain of tumorigenesis have implications for the regulation of telomerase expression and for the identification of cells that may be targets for malignant transformation. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. MIT, Whitehead Inst Biomed Res, Dept Biol, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Gerald, WL (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. EM geraldw@mskcc.org RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [CA 39826, CA 58596, CA 68273] NR 30 TC 311 Z9 337 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1998 VL 19 IS 2 BP 182 EP 186 DI 10.1038/554 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA ZQ468 UT WOS:000073865100029 PM 9620778 ER PT J AU Jain, RK AF Jain, RK TI The next frontier of molecular medicine: Delivery of therapeutics SO NATURE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. FU NCI NIH HHS [R35-CA-56591] NR 9 TC 280 Z9 288 U1 1 U2 21 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 1998 VL 4 IS 6 BP 655 EP 657 DI 10.1038/nm0698-655 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZR733 UT WOS:000074008300020 PM 9623964 ER PT J AU Lee, SJ Liyanage, U Bickel, PE Xia, WM Lansbury, PT Kosik, KS AF Lee, SJ Liyanage, U Bickel, PE Xia, WM Lansbury, PT Kosik, KS TI A detergent-insoluble membrane compartment contains A beta in vivo SO NATURE MEDICINE LA English DT Article ID DISEASE BRAIN; CAVEOLAE; DOMAINS; PROTEIN AB Ordered assembly of the amyloid-beta protein (A beta) into amyloid fibrils is a critical step in Alzheimer's disease (AD). To release the amyloidogenic peptide A beta from the Alzheimer amyloid precursor protein (APP), two secretases act sequentially: first, beta-secretase cleaves close to the membrane within the ectodomain and then gamma-secretase cuts within the transmembrane domain(1). The sites of gamma-secretase cleavage are after residues 40 or 42 of A beta. Except in those rare cases of AD caused by a mutation, levels of secreted A beta are not elevated; thus, the secretory pathway may be unaffected, and factors other than the extracellular concentration of A beta may contribute to the aggregation properties of the peptide. A beta is also present in intracellular compartments(2-5). The two gamma-secretase cleavage products, A beta 42 and A beta 40, were found in different compartments: A beta 42 in the endoplasmic reticulum (ER)/intermediate compartment(3-5), and A beta 40 in the trans-Golgi network(2,4) (TGN). The cellular compartments that harbor A beta are target sites for therapeutic intervention. Here we report that in the brain, the principal compartment in which A beta resides is a detergent-insoluble glycolipid-enriched membrane domain (DIG). Also present in the DIC fractions are the endoproteolytic fragments of presenilin-1 (PS1) and APP. The presence of these proteins, which all contribute to the generation of A beta, indicates that the DIG fraction is probably where the intramembranous cleavage of APP occurs. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kosik, KS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, 77 Ave Louis Pasteur,HIM, Boston, MA 02115 USA. EM lansbury@cnd.bwh.harvard.edu; Kosik@cnd.bwh.harvard.edu RI xia, weiming/E-5465-2016; OI xia, weiming/0000-0002-7463-3295; Lee, Seung-Jae/0000-0002-5155-5335 FU NIA NIH HHS [AG08470, AG06501] NR 35 TC 332 Z9 337 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 1998 VL 4 IS 6 BP 730 EP 734 DI 10.1038/nm0698-730 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZR733 UT WOS:000074008300043 PM 9623986 ER PT J AU Coggins, CH Lewis, JB Caggiula, AW Castaldo, LS Klahr, S Wang, SR AF Coggins, CH Lewis, JB Caggiula, AW Castaldo, LS Klahr, S Wang, SR TI Differences between women and men with chronic renal disease SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE gender; glomerular filtration rate; progression; renal disease ID DIETARY-PROTEIN RESTRICTION; BLOOD-PRESSURE CONTROL; FOLLOW-UP; PROGRESSION; HEALTH; FRAMINGHAM; IMPACT AB Background. The purpose of the present study was to compare the participation of women and men in the protocols of the Modification of Diet in Renal Disease (MDRD) study, a multicenter prospective randomized clinical trial, and to assess gender differences in their renal outcomes. Methods. Of the 840 participants in the MDRD study, 332 (39.5%) were women who were assigned randomly to the dietary protein and blood pressure groups and followed for a median of 2.2 years. A subgroup analysis of the MDRD study database was carried out to compare women and men participants in recruitment, baseline characteristics, adherence to protocol requirements, safety and outcomes, and progression of renal disease and its response to dietary and blood pressure interventions. Results. Adherence by women to the requirements of the protocol including diet, record keeping, office visits, glomerular filtration rate (GFR) measurements and urine collections was equivalent to that of men. Women had different renal diagnoses, less proteinuria and lower serum creatinine levels for given GFRs than men. When participants were grouped above and below age 52, the younger women had lower mean arterial pressure than did the men. Older women compared with younger had higher mean arterial pressure, body weight and body mass index, and total low density lipoprotein cholesterol. These differences were not seen between males of the same two age groups. During follow-up, the rate of GFR fall was slower in women, especially in the younger group. However, the association between gender and the rate of fall in GFR was attenuated and became non-significant after adjusting for differences in blood pressure, proteinuria and high density lipoprotein cholesterol. In analyses of the full cohort, there were no significant differences between women and men in the effects of the low protein or low blood pressure intervention in patients with either moderate (study A) or advanced (study B) renal disease. However, in subgroup analyses of patients in study A, there was some evidence of a lesser effect in women than in men. Conclusions. This exploratory analysis of the MDRD study indicates a slower mean GFR decline in women as compared with men. The slower mean GFR decline and suggestive evidence of a lesser beneficial effect of the low protein diet and low blood pressure interventions in women suggest that gender differences should be considered in trials of the effects of these interventions on the progression of renal disease. Also, the participation of women in the MDRD study was excellent and equivalent to that of men. C1 Cleveland Clin Fdn, Dept Biostat & Epidemiol, MDRD, Study Data Coordinating Ctr, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Vanderbilt Univ, Nashville, TN USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. RP Coggins, CH (reprint author), Cleveland Clin Fdn, Dept Biostat & Epidemiol, MDRD, Study Data Coordinating Ctr, P88,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 25 TC 74 Z9 77 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JUN PY 1998 VL 13 IS 6 BP 1430 EP 1437 DI 10.1093/ndt/13.6.1430 PG 8 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA ZR911 UT WOS:000074028300022 PM 9641172 ER PT J AU Endres, M Kaps, M Moskowitz, MA AF Endres, M Kaps, M Moskowitz, MA TI Apoptosis and cerebral ischemia SO NERVENARZT LA German DT Review DE apoptosis; cerebral ischemia; programmed cell death ID PROGRAMMED CELL-DEATH; INTERLEUKIN-1-BETA CONVERTING-ENZYME; NEURONAL APOPTOSIS; CYSTEINE PROTEASE; DNA FRAGMENTATION; IL-1-BETA-CONVERTING ENZYME; SUPEROXIDE-DISMUTASE; ICE/CED-3 PROTEASE; C-ELEGANS; BRAIN AB Apoptosis and programmed cell death have attracted major scientific interest during the last few years. Apoptosis can be differentiated from necrosis by means of morphological, biochemical, molecular and pharmacological parameters.Several molecular pathways leading to apoptosis have been elucidated over the last few years. Apoptosis is not only important for physiological cell turnover, but also plays a role in many pathological processes. Recently, a number of laboratories have found evidence of apoptotic cell death in cerebral ischemia in animal models.Quantitatively,apoptosis seems to be important in the border zone of the infarction,the so-called penumbra.Since parts of the apoptotic cascade can be inhibited, pharmacological treatment seems feasible. The so-called caspase inhibitors are promising therapeutic agents for the treatment of acute stroke and may be administered with other neuroprotective medications in humans in the near future. C1 Med Univ Lubeck, Neurol Klin, D-23538 Lubeck, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Neurol & Neurosurg Ser, Charlestown, MA USA. RP Endres, M (reprint author), Med Univ Lubeck, Neurol Klin, Ratzeburger Allee 160, D-23538 Lubeck, Germany. RI Moskowitz, Michael/D-9916-2011 NR 74 TC 1 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD JUN PY 1998 VL 69 IS 6 BP 459 EP 464 DI 10.1007/s001150050298 PG 14 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZW653 UT WOS:000074433200001 PM 9673968 ER PT J AU Martin, KA Welt, CK Taylor, AE Smith, JA Crowley, WF Hall, JE AF Martin, KA Welt, CK Taylor, AE Smith, JA Crowley, WF Hall, JE TI Is GnRH reduced at the midcycle surge in the human? Evidence from a GnRH-deficient model SO NEUROENDOCRINOLOGY LA English DT Article DE gonadotropins; gonadotropin-releasing hormone; gonadal steroids; estrous cycle; clinical neuroendocrinology ID GONADOTROPIN-RELEASING-HORMONE; HUMAN MENSTRUAL-CYCLE; RAT ESTROUS-CYCLE; LUTEINIZING-HORMONE; RHESUS-MONKEY; OVARIECTOMIZED EWES; PITUITARY-RESPONSIVENESS; PERIOVULATORY PERIOD; PULSATILE RELEASE; PULSE FREQUENCY AB Recent studies indicate that the midcycle gonadotropin surge in the human occurs without an increase in hypothalamic gonadotropin-releasing hormone (GnRH) pulse frequency. In addition, previous studies employing a GnRH antagonist to provide a semiquantitative estimate of endogenous GnRH secretion suggest that the overall amount of GnRH secreted is decreased at the time of the surge. To investigate the hypothesis that a normal gonadotropin surge can be generated in the human with a decreased amount of GnRH at the midcycle, 7 GnRH-deficient subjects underwent two cycles of a physiologic regimen of intravenous pulsatile GnRH therapy. In the control cycle, 75 ng/kg/bolus of GnRH, a dose known to be sufficient for folliculogenesis, was administered throughout the cycle, using physiological frequencies. In a second cycle, the bolus dose of GnRH was decreased by one-half log order to 25 ng/kg just prior to the luteinizing hormone surge and returned to 75 ng/kg after documented ovulation, All cycles were ovulatory. The peak luteinizing hormone level (77.4 +/- 9.7 vs. 67.5 +/- 17.6 IU/l) did not differ between the control and decreased GnRH cycles. There was no difference in the peak serum estradiol level (475.8 +/- 144.1 vs. 493.2 +/- 93.0 pg/ml), follicular phase length (15.0 +/- 1.3 vs. 14.8 +/- 0.6 days), or progesterone level (22.4 +/- 5.1 vs. 34.8 +/- 5.7 ng/ml) on day 6 of the luteal phase in the control and decreased GnRH cycles, respectively. Three pregnancies were achieved in each of the control and reduced GnRH cycles. We conclude that a decreased overall amount of GnRH generates a normal midcycle gonadotropin surge and has no significant impact on luteal phase adequacy or fertility. These results provide further evidence that a decrease in endogenous hypothalamic GnRH secretion may occur at the midcycle in normal women. This study also provides evidence that the GnRH requirements for normal follicular and luteal phase dynamics may well be greater than those required for generation of a normal midcycle gonadotropin surge and ovulation in women. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Natl Ctr Infertil Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. RP Martin, KA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Natl Ctr Infertil Res, Bartlett Hall,Fruit St, Boston, MA 02114 USA. OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [P30 HD028138, R01 HD015788, R01-HD-15080, T32 HD007396, U54-HD29164] NR 51 TC 12 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUN PY 1998 VL 67 IS 6 BP 363 EP 369 DI 10.1159/000054334 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA ZW636 UT WOS:000074431500001 PM 9662715 ER PT J AU Filley, CM AF Filley, CM TI The behavioral neurology of cerebral white matter SO NEUROLOGY LA English DT Review ID PROGRESSIVE MULTIPLE-SCLEROSIS; CENTRAL NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; TOLUENE ABUSE; MRI FINDINGS; DEMENTIA; CONDUCTION; DISORDERS; REMYELINATION; INVOLVEMENT AB Behavioral neurology has primarily focused on brain-behavior relations as revealed by disorders of the cerebral cortex and subcortical gray matter. Disorders of cerebral white matter have received less attention. This article considers the contribution of cerebral white matter to normal behavioral function and the effects of white matter disorders on behavior. Diffuse dysfunction is more common than focal impairment, and the term white matter dementia has been proposed as a clinical entity. Conventional neuroimaging has enabled more accurate identification of white matter regions participating in neurobehavioral operations, and newer imaging techniques may define white matter connectivity within and between the hemispheres. As an essential component of neural networks, cerebral white matter contributes to cognitive and emotional functions, and lesions of white matter disconnect these networks to produce neurobehavioral syndromes. C1 Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Filley, CM (reprint author), Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, UCHSC B-183,4200 E 9th Ave, Denver, CO 80262 USA. NR 54 TC 107 Z9 108 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1998 VL 50 IS 6 BP 1535 EP 1540 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA ZU712 UT WOS:000074226700006 PM 9633691 ER PT J AU Johnson, KA Jones, K Holman, BL Becker, JA Spiers, PA Satlin, A Albert, MS AF Johnson, KA Jones, K Holman, BL Becker, JA Spiers, PA Satlin, A Albert, MS TI Preclinical prediction of Alzheimer's disease using SPECT SO NEUROLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; APOLIPOPROTEIN-E; RHESUS-MONKEY; BLOOD-FLOW; HIPPOCAMPAL; DEMENTIA; ALLELE; MEMORY; ABNORMALITIES AB Background: Regional cerebral perfusion measured by single photon emission computed tomography (SPECT) was examined as a preclinical predictor of the development of Alzheimer's disease (AD). Methods: Singular value decomposition was used to produce 20 SPECT factors (known as vectors) (n = 152). Vector scores were then computed for four groups (n = 136), differing in cognitive status: Group 1-normal controls at both baseline and follow-up; Group 2-subjects with "questionable" AD at both baseline and follow-up; Group 3-subjects with questionable AD at baseline who converted to AD on follow-up (Converters); Group 4-subjects with AD at baseline. All SPECT data in the analyses were gathered at baseline. Results: The four groups could be distinguished on the basis of their baseline SPECT data (p less than or equal to 0.00005; hit rate = 83%), Regional decreases in perfusion were most prominent among Converters in the hippocampalamygdaloid complex, the posterior cingulate, the anterior thalamus, and the anterior cingulate. Inclusion of apolipoprotein E status did not significantly improve the discrimination. Conclusions: SPECT data gathered and analyzed in this manner may be useful as one aspect of the preclinical prediction of AD. Three of the four brain regions important for discriminating Converters from normal controls involve a distributed brain network pertaining to memory, suggesting that this network may be selectively affected in the earliest stages of AD. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Boston, MA USA. Brandeis Univ, Florence Heller Sch Adv Studies Social Welf, Waltham, MA 02254 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. RP Johnson, KA (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. FU NCRR NIH HHS [M01RR00088]; NIA NIH HHS [P01-AG04953, R01-AG09301] NR 60 TC 340 Z9 356 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1998 VL 50 IS 6 BP 1563 EP 1571 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA ZU712 UT WOS:000074226700010 PM 9633695 ER PT J AU Tracey, I Hamberg, LM Guimaraes, AR Hunter, G Chang, I Navia, BA Gonzalez, RG AF Tracey, I Hamberg, LM Guimaraes, AR Hunter, G Chang, I Navia, BA Gonzalez, RG TI Increased cerebral blood volume in HIV-positive patients detected by functional MRI SO NEUROLOGY LA English DT Article ID AIDS DEMENTIA COMPLEX; IMMUNODEFICIENCY-VIRUS-INFECTION; POSITRON-EMISSION-TOMOGRAPHY; NITRIC-OXIDE SYNTHASE; D-ASPARTATE RECEPTORS; COMPUTED-TOMOGRAPHY; NEOCORTICAL DAMAGE; FRONTAL-CORTEX; BRAIN; FLOW AB Objective: To study changes in cerebral hemodynamics related to HIV infection. Background: Cerebral injury is a well-known manifestation of HIV infection. Physiologic changes in the HIV brain may precede structural changes and may be detected by functional MRI (fMRI). Methods: Dynamic contrast fMRI was used to measure the cerebral blood volume (CBV) in 13 patients infected with HIV and in 7 healthy control subjects. Results: Significant increases in dynamic CBV were found in the deep (p < 0.001) and cortical gray matter (p < 0.05) of HIV-positive (HIV+) patients. Patients with definite cognitive impairment showed significantly greater increases in CBV in the deep gray matter (DGM) compared with those without impairment. In one patient with rapidly progressive cognitive impairment, these abnormalities reversed and paralleled clinical improvement after initiation of zidovudine monotherapy. Conclusions: This study supports the hypothesis that HIV infection is associated with significant cerebral hemodynamic changes, particularly in the DGM, that may contribute to cognitive dysfunction in AIDS. Functional MRI may be useful for early detection of cerebral injury and for the assessment of novel therapies. C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Serv Neurol, Boston, MA USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB285,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR13212]; NINDS NIH HHS [NS34626] NR 45 TC 49 Z9 51 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1998 VL 50 IS 6 BP 1821 EP 1826 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA ZU712 UT WOS:000074226700049 PM 9633734 ER PT J AU Hollenbach, E Ackermann, S Hyman, BT Rebeck, GW AF Hollenbach, E Ackermann, S Hyman, BT Rebeck, GW TI Confirmation of an association between a polymorphism in exon 3 of the low-density lipoprotein receptor-related protein gene and Alzheimer's disease SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E AB C766T, a polymorphism in exon 3 of the gene for the low-density lipoprotein receptor-related protein (LRP), was found to be associated with late-onset Alzheimer's disease (AD). We developed a PCR-restriction enzyme-based assay to analyze this allele in 234 AD patients and 103 controls. We confirmed that the LRP C766T polymorphism was in disequilibrium with AD-the C/C genotype was present in 76% of AD patients and 60% of controls (p < 0.01); however, the LRP polymorphism did not influence age at onset of AD. C1 Massachusetts Gen Hosp, Alzheimers Res Unit, Charlestown, MA 02129 USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimers Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG05134, AG12406, AG14473] NR 10 TC 100 Z9 105 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1998 VL 50 IS 6 BP 1905 EP 1907 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA ZU712 UT WOS:000074226700074 PM 9633759 ER PT J AU Shafqat, S Elkind, MSV Chiocca, EA Takeoka, M Koroshetz, WJ AF Shafqat, S Elkind, MSV Chiocca, EA Takeoka, M Koroshetz, WJ TI Petroclival meningioma presenting with pathological laughter SO NEUROLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Shafqat, S (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurol ACC 835, Boston, MA 02114 USA. NR 7 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1998 VL 50 IS 6 BP 1918 EP 1919 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA ZU712 UT WOS:000074226700079 PM 9633764 ER PT J AU Woolf, CJ Mannion, RJ Neumann, S AF Woolf, CJ Mannion, RJ Neumann, S TI Null mutations lacking substance: Elucidating pain mechanisms by genetic pharmacology SO NEURON LA English DT Review ID MOLECULAR CHARACTERIZATION; FUNCTIONAL CDNA; P RECEPTOR; HYPERSENSITIVITY; ANTAGONISTS; NEURONS C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown Navy Yard, Charlestown, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. NR 19 TC 43 Z9 43 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN PY 1998 VL 20 IS 6 BP 1063 EP 1066 DI 10.1016/S0896-6273(00)80487-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ZY493 UT WOS:000074627300003 PM 9655494 ER PT J AU Zylka, MJ Shearman, LP Weaver, DR Reppert, SM AF Zylka, MJ Shearman, LP Weaver, DR Reppert, SM TI Three period homologs in mammals: Differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain SO NEURON LA English DT Article ID EXPRESSION; RHYTHMS AB We have cloned and characterized the mouse cDNA of a third mammalian homolog of the Drosophila period gene and designated it mPer3. The mPER3 protein shows similar to 37% amino acid identity with mPER1 and mPER2 proteins. The three mammalian PER proteins share several regions of sequence homology, and each contains a protein dimerization PAS domain. mPer3 RNA levels oscillate in the suprachiasmatic nuclei (SCN) and eyes. In the SCN, mPer3 RNA levels are not acutely altered by light exposure at different times during subjective night. This contrasts with the acute induction by light of mPer1 and mPer2 RNA levels during early and late subjective night. mPer3 is widely expressed in tissues outside of brain. In liver, skeletal muscle, and testis, mPer RNAs exhibit prominent, synchronous circadian oscillations. The results highlight the differential light responses among the three mammalian Per genes in the SCN and raise the possibility of circadian oscillators in mammals outside of brain and retina. C1 Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. OI Weaver, David/0000-0001-7941-6719 FU NICHD NIH HHS [R37 HD14427]; NIMH NIH HHS [MH11547] NR 24 TC 641 Z9 651 U1 0 U2 25 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN PY 1998 VL 20 IS 6 BP 1103 EP 1110 DI 10.1016/S0896-6273(00)80492-4 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZY493 UT WOS:000074627300007 PM 9655499 ER PT J AU Garcia-Anoveros, J Garcia, JA Liu, JD Corey, DP AF Garcia-Anoveros, J Garcia, JA Liu, JD Corey, DP TI The nematode degenerin UNC-105 forms ion channels that are activated by degeneration- or hypercontraction-causing mutations SO NEURON LA English DT Article ID SENSITIVE NA+ CHANNEL; CAENORHABDITIS-ELEGANS; ESCHERICHIA-COLI; K+ CHANNELS; C-ELEGANS; NEURONAL DEGENERATION; MOLECULAR-CLONING; SODIUM-CHANNEL; CATION CHANNEL; HAIR-CELLS AB Nematode degenerins have been implicated in touch sensitivity and other forms of mechanosensation. Certain mutations in several degenerin genes cause the swelling, vacuolation, and death of neurons, and other mutations in the muscle degenerin gene unc-105 cause hypercontraction. Here, we confirm that unc-105 encodes an ion channel and show that it is constitutively active when mutated. These mutations disrupt different regions of the channel and have different effects on its gating. The UNC-105 channels are permeable to small monovalent cations but show voltage-dependent block by Ca2+ and Mg2+. Amiloride also produces voltage-dependent block, consistent with a single binding site 65% into the electric field. Mammalian cells expressing the mutant channels accumulate membranous whorls and multicompartment vacuoles, hallmarks of degenerin-induced cell death across species. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Neurobiol, Boston, MA 02114 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. RP Corey, DP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Neurobiol, Boston, MA 02114 USA. OI Corey, David/0000-0003-4497-6016 NR 66 TC 69 Z9 74 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN PY 1998 VL 20 IS 6 BP 1231 EP 1241 DI 10.1016/S0896-6273(00)80503-6 PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZY493 UT WOS:000074627300018 PM 9655510 ER PT J AU Yamada, K Shrier, DA Tanaka, H Numaguchi, Y AF Yamada, K Shrier, DA Tanaka, H Numaguchi, Y TI A case of subacute combined degeneration: MRI findings SO NEURORADIOLOGY LA English DT Article DE spine; cervical spinal cord; posterior column; subacute combined degeneration; vitamin B12 deficiency; degenerative process; magnetic resonance imaging ID SPINAL-CORD; COBALAMIN AB The specific spinal cord lesion caused by vitamin B12 deficiency is known as subacute combined degeneration (SCD). Neuropathological studies of SCD show lesions mainly in the posterior and lateral columns, involving the cortico-spinal and spine-cerebellar tracts. We report a case of SCD in a 19-year-old man who presented with 4 weeks history of gradually progressing tingling in both hands. MRI of the cervical spine demonstrated symmetrical areas of T2 signal abnormality involving the dorsal columns of the cervical cord from the C2 through C5 levels associated with spinal cord expansion. He was treated with vitamin B12 supplements and experienced gradual improvement in his clinical symptoms. Repeat MRI of the cervical spine after 2 months revealed slight decrease in the area of abnormal signal. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Univ Rochester, Med Ctr, Dept Diagnost Radiol, Rochester, NY 14642 USA. RP Yamada, K (reprint author), Massachusetts Gen Hosp, NMR Ctr, 13th St,Bldg 149, Charlestown, MA 02129 USA. NR 11 TC 25 Z9 28 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD JUN PY 1998 VL 40 IS 6 BP 398 EP 400 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZY487 UT WOS:000074626700014 PM 9689633 ER PT J AU Amin-Hanjani, S Ogilvy, CS Ojemann, RG Crowell, RM AF Amin-Hanjani, S Ogilvy, CS Ojemann, RG Crowell, RM TI Risks of surgical management for cavernous malformations of the nervous system SO NEUROSURGERY LA English DT Article DE cavernous malformation; hemorrhage; seizure; surgical risk ID CEREBRAL VASCULAR MALFORMATIONS; BRAIN-STEM; SPINAL-CORD; NATURAL-HISTORY; ANGIOMAS; RESECTION AB OBJECTIVE: As more information evolves regarding the natural history of cavernous malformations (CMs), the risks of operative intervention must be balanced against nonoperative management. in an attempt to better delineate the surgical risks for operable CMs, we undertook a retrospective analysis of 94 patients with 97 CMs surgically excised at the Massachusetts General Hospital. METHODS: Data regarding surgical complications and outcome measures, including neurological status and seizure outcome, were analyzed. RESULTS: The incidence of transient neurological morbidity was 20.6%, but only 4 of the 97 operations (4.1%) resulted in persistent disabling neurological complications and 2 (2.1%) in nondisabling deficits. There was no operative mortality. Brain stem lesions (n = 14) were associated with the highest incidence of neurological complications, both transient and persistent (odds ratio, 4.8; 95% confidence interval, 1.5-15.7). The overall neurological outcome was excellent or good in 89.7% of all lesions: 96.8% of lobar CMs (n = 63), 64.2% of brain stem CMs (n = 14), 87.5% of cerebellar CMs (n = 8), 100% of cranial nerve CMs (n = 4), and 75% of spinal cord CMs (n = 8). Patients with brain stem and spinal cord CMs were in poorer preoperative neurological condition than were patients with CMs in other locations and therefore had a significantly reduced level of function after surgery (P < 0.01). There was improvement in 35.7% of the patients with brain stem lesions and 62.5% of the patients with spinal cord lesions after surgery. In the 38 patients presenting with seizures, 97% were seizure-free after surgery. CONCLUSION: The risks of operative management of CMs varies based on location. When evaluating patients with operable CMs for surgery, the incidence of complications as well as final neurological outcome should be carefully weighed against the existing knowledge of the natural history of lesions managed expectantly. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Neurosurg Serv, Worcester, MA USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, VBK 710,32 Fruit St, Boston, MA 02114 USA. NR 40 TC 70 Z9 75 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1998 VL 42 IS 6 BP 1220 EP 1227 DI 10.1097/00006123-199806000-00007 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZR050 UT WOS:000073930700007 PM 9632179 ER PT J AU Amin-Hanjani, S Ogilvy, CS Candia, GJ Lyons, S Chapman, PH AF Amin-Hanjani, S Ogilvy, CS Candia, GJ Lyons, S Chapman, PH TI Stereotactic radiosurgery for cavernous malformations: Kjellberg's experience with proton beam therapy in 98 cases at the Harvard cyclotron SO NEUROSURGERY LA English DT Article DE cavernous malformation; hemorrhage; neurological disability; proton beam; seizure; stereotactic radiosurgery ID OCCULT VASCULAR MALFORMATIONS; BRAIN-STEM; NATURAL-HISTORY; ANGIOMAS; MANAGEMENT; DIAGNOSIS AB OBJECTIVE: The lack of treatment options for surgically inaccessible cavernous malformations has made radiosurgery a possible alternative to conservative management. The few previous reports of radiosurgical efficacy have been limited by small numbers, short follow-up, or lack of attention to the full spectrum of end points, including neurological disability. In an attempt to elucidate the risk-to-benefit ratio of radiosurgery for cavernous malformations, we undertook a retrospective analysis of of 95 patients with 98 lesions treated by the late Raymond N. Kjellberg. METHODS: Patients were followed for an average of 5.4 years (range, 0.3-12.3 yr), and data regarding hemorrhage, seizure, neurological disability, and incidence of radiation-induced complications were gathered. RESULTS: The analysis revealed a drop in annual hemorrhage rates from 17.3% per lesion per year before treatment to 4.5% per lesion per year after a latency period of 2 years. Improvement in seizure control was evident. However, a 16% incidence of permanent neurological deficit and a 3% mortality rate were attributable to radiographically confirmed radiation-induced complications. Neurological disability scores, measured by the modified Rankin disability scale, indicated a significant decline in neurological functioning during the follow-up interval, a result of the combined effects of radiation-related injury, hemorrhage, and clinical progression of the lesion. CONCLUSION: We conclude that although radiosurgery does seem to reduce hemorrhage, there is potential for complications and continued lesion progression after radiosurgery. These risks and benefits must be carefully balanced against the natural history of untreated lesions if the use of radiosurgery is considered. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, VBK 710,32 Fruit St, Boston, MA 02114 USA. NR 32 TC 110 Z9 115 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1998 VL 42 IS 6 BP 1229 EP 1236 DI 10.1097/00006123-199806000-00013 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZR050 UT WOS:000073930700012 PM 9632180 ER PT J AU Butler, WE Piaggio, CM Constantinou, C Niklason, L Gonzalez, RG Cosgrove, GR Zervas, NT AF Butler, WE Piaggio, CM Constantinou, C Niklason, L Gonzalez, RG Cosgrove, GR Zervas, NT TI A mobile computed tomographic scanner with intraoperative and intensive care unit applications SO NEUROSURGERY LA English DT Article DE head fixation; instrumentation; intraoperative computed tomography AB INTRODUCTION: A mobile computed tomographic scanner has been developed in which the scan plane is selected by means of gantry translation, rather than by translation of the patient table. This permits computed tomographic scanning in situ of any patient who is positioned on a radiolucent surface that fits within the inner diameter of the gantry. We report the design of and initial experience with this scanner as used with adapters for intraoperative and bedside computed tomography (CT). METHODS: The scanner is equipped with wheels, draws power from wall outlets (120 V, 20 A) in combination with batteries, and has a translating gantry. Preclinical studies of image quality were performed with phantoms. An operating table adapter was built for use with a radiolucent cranial fixation device. A bedside adapter was built that holds the head and shoulders of a patient in the intensive care unit. RESULTS: The preclinical phantom studies showed satisfactory image spatial resolution (0.8 mm) and low-contrast resolution signal-to-noise relative standard deviation (0.37%). Experience to date with 12 patients has confirmed the feasibility of intraoperative CT on demand. Experience to date with 26 patients has confirmed the feasibility of routine bedside CT in the intensive care unit. CONCLUSION: With these adaptations, mobile CT may increase the efficiency of intraoperative scanning by making it available to multiple operating rooms without committing it to any room for an entire operation and may increase the efficiency and safety of CT of critically ill patients who currently need to leave the intensive cave unit to travel to a fixed CT installation and back. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Butler, WE (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Wang 331,15 Parkman St, Boston, MA 02114 USA. NR 10 TC 81 Z9 81 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JUN PY 1998 VL 42 IS 6 BP 1304 EP 1310 DI 10.1097/00006123-199806000-00064 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZR050 UT WOS:000073930700060 PM 9632189 ER PT J AU Okano, M Xie, SP Li, E AF Okano, M Xie, SP Li, E TI Dnmt2 is not required for de novo and maintenance methylation of viral DNA in embryonic stem cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; METHYLTRANSFERASE; ACTIVATION; MISMATCHES; BASE; HHAI AB We have shown previously that de novo methylation activities persist in mouse embryonic stem (ES) cells homozygous for a null mutation of Dnmt1 that encodes the major DNA cytosine methyltransferase. In this study, we have cloned a putative mammalian DNA methyltransferase gene, termed Dnmt2, that is homologous to pmt1 of fission yeast. Different from pmt1 in which the catalytic Pro-Pro-Cys (PPC) motif is 'mutated' to Pro-Ser-Cys, Dnmt2 contains all the conserved methyltransferase motifs, thus likely encoding a functional cytosine methyltransferase. However, baculovirus-expressed Dnmt2 protein failed to methylate DNA in vitro. To investigate whether Dnmt2 functions as a DNA methyltransferase in vivo, we inactivated the Dnmt2 gene by targeted deletion of the putative catalytic PPC motif in ES cells. We showed that endogenous virus was fully methylated in Dnmt2-deficient mutant ES cells. Furthermore, newly integrated retrovirus DNA was methylated de novo in infected mutant ES cells as efficiently as in wild-type cells. These results indicate that Dnmt2 is not essential for global de novo or maintenance methylation of DNA in ES cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Li, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM en@cvrc.mgh.harvard.edu FU NIGMS NIH HHS [GM52106] NR 24 TC 265 Z9 284 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUN 1 PY 1998 VL 26 IS 11 BP 2536 EP 2540 DI 10.1093/nar/26.11.2536 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZU005 UT WOS:000074151700004 PM 9592134 ER PT J AU Haas, LB AF Haas, LB TI Pathophysiology of diabetes mellitus SO NURSE PRACTITIONER FORUM-CURRENT TOPICS AND COMMUNICATIONS LA English DT Article ID BETA-CELL; INSULIN-RESISTANCE; GLUCOSE TOXICITY AB The most common types of diabetes observed in a primary care practice are type 1,type 2, and gestational diabetes. Type 1 diabetes is an autoimmune disease characterized by total destruction of the pancreatic beta cells, whereas insulin resistance, impaired insulin secretion, and inappropriate hepatic glucose secretion characterize type 2 diabetes. Gestational diabetes is similar to type 2 diabetes, but is first diagnosed during pregnancy. This is a US government work. There are no restrictions on its use. C1 VA Puget Sound HCS, Seattle Div, Seattle, WA 98108 USA. RP Haas, LB (reprint author), VA Puget Sound HCS, Seattle Div, 1660 S Columbian Way,118, Seattle, WA 98108 USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1045-5485 J9 NURS PRACT FORUM JI Nurse Pract. Forum-Curr. Top. Commun. PD JUN PY 1998 VL 9 IS 2 BP 42 EP 45 PG 4 WC Nursing SC Nursing GA 106JR UT WOS:000075126600004 PM 9752116 ER PT J AU Scully, RE AF Scully, RE TI Extraovarian primary peritoneal carcinoma SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID SEROUS BORDERLINE TUMORS C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Scully, RE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUN PY 1998 VL 12 IS 6 BP 820 EP + PG 2 WC Oncology SC Oncology GA ZX680 UT WOS:000074543200008 ER PT J AU Alino, AM Perry, HD Kanellopoulos, AJ Donnenfeld, ED Rahn, EK AF Alino, AM Perry, HD Kanellopoulos, AJ Donnenfeld, ED Rahn, EK TI Conjunctival flaps SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of American-Academy-of-Ophthalmology CY OCT 29-NOV 02, 1995 CL ATLANTA, GEORGIA SP Amer Acad Ophthalmol ID MANAGEMENT; ULCERS AB Purpose: The authors reviewed their experience with total conjunctival flaps (TCF) and partial conjunctival flaps (PCF) for the past 5 years in 61 patients. Methods: Forty-eight patients had TCF and 13 had PCF. Diagnoses for surgery included severe bullous keratopathy for chronic graft failure (not candidates for keratoplasty) (19), herpes tester ophthalmicus (7), chronic ulcerative keratitis (14), neurotrophic keratitis (2), and herpes simplex keratitis (9). Results: There were seven complications. Four flap retractions occurred in the TCF group, requiring resuturing in two. Three complications occurred in the PCF group. One patient had two flap retractions and recurrent ulceration, requiring tarsorrhaphy. One patient with PCF suffered a perforation after flap retraction, necessitating penetrating keratoplasty. Conclusion: The authors believe conjunctival flaps are underused and should be considered seriously for bullous keratopathy, neurotrophic keratitis, recalcitrant keratitis, and persistent nonhealing epithelial defects. C1 N Shore Univ Hosp, Lions Eye Bank Long Isl, Manhasset, NY 11030 USA. Nassau Cty Med Ctr, Dept Ophthalmol, E Meadow, NY 11554 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. New York Univ Hosp, New York, NY USA. New York Eye & Ear Infirm, Dept Ophthalmol, New York, NY 10003 USA. Manhattan Eye Ear & Throat Hosp, Dept Ophthalmol, New York, NY 10021 USA. RP Perry, HD (reprint author), N Shore Univ Hosp, Lions Eye Bank Long Isl, 300 Community Dr, Manhasset, NY 11030 USA. NR 16 TC 40 Z9 44 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JUN PY 1998 VL 105 IS 6 BP 1120 EP 1123 DI 10.1016/S0161-6420(98)96017-1 PG 4 WC Ophthalmology SC Ophthalmology GA ZR726 UT WOS:000074007600047 PM 9627666 ER PT J AU Dibart, S Eftimiadi, C Socransky, S Taubman, MA Van Dyke, TE AF Dibart, S Eftimiadi, C Socransky, S Taubman, MA Van Dyke, TE TI Rapid evaluation of serum and gingival crevicular fluid immunoglobulin G subclass antibody levels in patients with early-onset periodontitis using checkerboard immunoblotting SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE early-onset periodontitis; Actinobacillus actinomycetemcomitans; IgG subclass ID LOCALIZED JUVENILE PERIODONTITIS; GENERALIZED SEVERE PERIODONTITIS; HUMAN IMMUNE-RESPONSES; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; ORAL MICROORGANISMS; YOUNG-ADULTS; DISEASE; ANTIGENS; TITERS AB A method was developed to evaluate the presence of immunoglobulin G (IgC) subclass (1-4) antibody to Actinobacillus actinomycetemcomitans, serotype b (strain Y4) in patients with early-onset periodontitis on a single nitrocellulose membrane. Sera from 30 early-onset periodontitis patients and gingival crevicular fluid samples from 2 patients were collected and tested with four different preparations of A. actinomycetemcomitans (Y4). The principle steps of the assay are: a) binding of the bacterial antigen (Y4) and the anti-human IgG antibody (capture antibody) in parallel lanes on nitrocellulose membranes; b) incubation of known concentrations of the IgC subclasses 1, 2, 3 and 4, as well as a dilution of serum and/or gingival crevicular fluid from patients in lanes perpendicular to the antigen lanes; c) incubation of the membranes with the corresponding peroxidase conjugated anti-human IgG subclass secondary antibody; d) detection of positive signals by enhanced chemiluminescence. The blots were evaluated by visual comparison to a series of blots containing known concentrations of IgG subclasses. The method was used to rapidly screen a relatively large number of patient sera and gingival crevicular fluid samples for IgG subclasses in a cost-effective assay. The predominant IgG subclass found in early-onset periodontitis was IgG2. C1 Boston Univ, Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. Univ Genoa, Sch Dent, Dept Periodontol, Genoa, Italy. Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RP Dibart, S (reprint author), Boston Univ, Sch Dent Med, Dept Periodontol & Oral Biol, 100 E Newton St, Boston, MA 02118 USA. RI Eftimiadi, Costantino/F-3491-2015 OI Eftimiadi, Costantino/0000-0003-1510-4614 FU NIDCR NIH HHS [DE-03420, DE-06436, DE-04881] NR 29 TC 12 Z9 12 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD JUN PY 1998 VL 13 IS 3 BP 166 EP 172 DI 10.1111/j.1399-302X.1998.tb00728.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA ZU722 UT WOS:000074227800005 PM 10093531 ER PT J AU Jainkittivong, A Johnson, DA Yeh, CK AF Jainkittivong, A Johnson, DA Yeh, CK TI The relationship between salivary histatin levels and oral yeast carriage SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE histatins; Candida; yeast; saliva ID HISTIDINE-RICH-POLYPEPTIDES; HUMAN-PAROTID-SALIVA; CANDIDA-ALBICANS; HIV-1 INFECTION; FLOW-RATE; SECRETION; PROTEINS; VARIANTS AB Candida species are common commensal inhabitants of the oral cavity. Human saliva contains antifungal proteins called histatins. We tested the hypothesis that oral yeast status is related to salivary histatin levels. Thirty subjects were divided into two groups based on the presence (n=15) or absence (n=15) of yeast on oral mucosa surfaces. Unstimulated and stimulated submandibular and sublingual and parotid saliva was collected from each subject. Salivary flow rates were measured and histatin concentrations were determined in the stimulated saliva samples. The yeast colony positive group showed lower median unstimulated parotid saliva flow rates as well as lower median concentrations of total histatins in submandibular and sublingual saliva. There was a negative correlation between yeast colony-forming units and unstimulated parotid saliva flow rates and between yeast colony-forming units and submandibular and sublingual saliva histatin concentration and secretion. The results suggest that oral yeast status may be influenced by unstimulated parotid saliva flow rates and by submandibular and sublingual histatin concentration and secretion. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78284 USA. Chulalongkorn Univ, Fac Dent, Dept Oral Med, Bangkok, Thailand. 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. RP Yeh, CK (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIDCR NIH HHS [DE 10756] NR 32 TC 30 Z9 32 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD JUN PY 1998 VL 13 IS 3 BP 181 EP 187 DI 10.1111/j.1399-302X.1998.tb00730.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA ZU722 UT WOS:000074227800007 PM 10093533 ER PT J AU McGrory, BJ Estok, DM Harris, WH AF McGrory, BJ Estok, DM Harris, WH TI Follow-up of intertrochanter osteotomy of the hip during a 25-year period SO ORTHOPEDICS LA English DT Article AB In 1984, in reporting follow-up on 67 hips in 61 patients who underwent intertrochanteric osteotomies for osteoarthritis of the hip, we found that between 12 and 15 years after osteotomy, 34% (23) of the 67 hips remained functional and the remainder had been converted to an arthroplasty. We now report on the fate of those osteotomies over a 25-year period. Ten patients with 10 osteotomies did not require an arthroplasty, having died without requiring conversion to total hip arthroplasty at an average of 18.3 years after osteotomy (range: 11 to 24.1 years). Two others were living at an average of 25.2 years after osteotomy without requiring conversion. Thus, for 18% of the hips, no further hip surgery was performed. For the remaining 55 hips in 49 patients, the osteotomy had served for an average of 9.8 years (range: 1.3 to 26.1 years) before requiring arthroplasty. The cumulative probability of osteotomy survival was 57.8% (standard error: 6.0%) at 10 years, 20.0% (standard error: 4.9%) at 20 years, and 5.7% (standard error: 2.9%) at 25 years by Kaplan-Meier survivorship analysis. C1 Orthopaed Associates Portland PA, Portland, ME USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, GrJ 1126,32 Fruit St, Boston, MA 02114 USA. NR 6 TC 9 Z9 9 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD JUN PY 1998 VL 21 IS 6 BP 651 EP 653 PG 3 WC Orthopedics SC Orthopedics GA ZV532 UT WOS:000074314200005 PM 9642703 ER PT J AU Dray, TG Hillel, AD Miller, RM AF Dray, TG Hillel, AD Miller, RM TI Dysphagia caused by neurologic deficits SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID AMYOTROPHIC LATERAL SCLEROSIS; LARYNGEAL NERVE PARALYSIS; BRAIN-STEM STROKE; MULTIPLE-SCLEROSIS; PARKINSONS-DISEASE; MYASTHENIA-GRAVIS; DISORDERS; PHYSIOLOGY; MANAGEMENT; ASPIRATION AB This article provides a brief review of the neurophysiology behind the normal swallow. The examination and work-up of a patient with dysphagia is then detailed. Finally, the major neurologic conditions associated with dysphagia are considered. C1 VA Puget Sound Hlth Care Syst, Dept Speech Pathol & Audiol, Seattle, WA 98108 USA. Univ Washington, Med Ctr, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. RP Miller, RM (reprint author), VA Puget Sound Hlth Care Syst, Dept Speech Pathol & Audiol, 1660 Columbia Way S, Seattle, WA 98108 USA. NR 62 TC 27 Z9 31 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD JUN PY 1998 VL 31 IS 3 BP 507 EP + DI 10.1016/S0030-6665(05)70067-0 PG 19 WC Otorhinolaryngology SC Otorhinolaryngology GA ZZ594 UT WOS:000074745800009 PM 9628947 ER PT J AU Whittemore, KR Merchant, SN Rosowski, JJ AF Whittemore, KR Merchant, SN Rosowski, JJ TI Acoustic mechanisms: Canal wall-up versus canal wall-down mastoidectomy SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID MIDDLE-EAR; CHOLESTEATOMA; IMPEDANCE AB The contribution of the middle ear air spaces to sound transmission through the middle ear in canal wall-up and canal wall-down mastoidectomy was studied in human temporal bones by measurements of middle ear input impedance and sound pressure difference across the tympanic membrane for the frequency range 50 Hz to 5 kHz. These measurements indicate that, relative to canal wall-up procedures, canal wall-down mastoidectomy results in a 1 to 5 dB decrease in middle ear sound transmission below 1 kHz, a 0 to 10 dB increase between 1 and 3 kHz, and no change above 3 kHz, These results are consistent with those reported by Gyo et at. (Arch Otolaryngol Head Neck Surg 1986; 112:1262-8), in which umbo displacement was used as a measure of sound transmission, A model analysis suggests that the reduction in sound transmission below 1 kHz can be explained by the smaller middle ear air space volume associated with the canal wall-down procedure. We conclude that as long as the middle ear air space is aerated and has a volume greater than 0.7 ml, canal wall-down mastoidectomy should generally cause less than 10 dB changes in middle ear sound transmission relative to the canal wall-up procedure. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [K08-DC00088, P01-DC00119] NR 16 TC 22 Z9 23 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 1998 VL 118 IS 6 BP 751 EP 761 DI 10.1016/S0194-5998(98)70264-5 PG 11 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA ZT295 UT WOS:000074070200004 PM 9627232 ER PT J AU Elenberg, E Norling, LL Kleinman, RE Ingelfinger, JR AF Elenberg, E Norling, LL Kleinman, RE Ingelfinger, JR TI Feeding problems in cystinosis SO PEDIATRIC NEPHROLOGY LA English DT Article DE cystinosis; feeding problems; gastrointestinal dysfunction; nutrition support; treatment of gastrointestinal problems ID NEPHROPATHIC CYSTINOSIS; GROWTH-HORMONE; RENAL-FUNCTION; CYSTEAMINE; INDOMETHACIN; CHILDREN; RAT AB Nephropathic cystinosis, a rare autosomal recessive storage disease characterized by intracellular storage of free cystine due to a defect in lysosomal cystine transport, is the most common cause of Fanconi syndrome in childhood. Although manifestations of extrarenal organ involvement during the course of the disease are diverse, the spectrum of gastrointestinal (GI) problems has not yet been examined. In responses to a questionnaire from 70 (35%) of the 200 registered members of the Cystinosis Foundation, we found that GI symptoms are more common, more diverse, and occur at a younger age in patients with cystinosis than previously recognized. Ninety-three percent of interviewed subjects had GI symptoms at initial presentation, and the overall lifetime prevalence of GI problems in this group was 100%. Thirty percent have received gastric/jejunal tube feedings, and 7% required continuous or intermittent total parenteral nutrition. Fifty percent have been formally tested for GI abnormalities, and among these 77% have documented functional abnormalities (reflux/dysmotility, pseudo-obstruction, swallowing dysfunction). Early recognition and aggressive therapy of GI problems in cystinotic patients may ameliorate or prevent the development of disabling symptoms. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Div Nephrol, Boston, MA 02114 USA. RP Ingelfinger, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Div Nephrol, ACC-709,Fruit St, Boston, MA 02114 USA. NR 14 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JUN PY 1998 VL 12 IS 5 BP 365 EP 370 PG 6 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA ZZ510 UT WOS:000074736600004 PM 9686953 ER PT J AU Bergeron, BP AF Bergeron, BP TI The effect of technology on the written tradition of medicine SO PERSPECTIVES IN BIOLOGY AND MEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Med Informat Lab, Boston, MA 02114 USA. RP Bergeron, BP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Med Informat Lab, Fruit St, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0031-5982 J9 PERSPECT BIOL MED JI Perspect. Biol. Med. PD SUM PY 1998 VL 41 IS 4 BP 572 EP 578 PG 7 WC History & Philosophy Of Science; Medicine, Research & Experimental SC History & Philosophy of Science; Research & Experimental Medicine GA 113WK UT WOS:000075576700011 ER PT J AU Harmar, AJ Arimura, A Gozes, I Journot, L Laburthe, M Pisegna, JR Rawlings, SR Robberecht, P Said, SI Sreedharan, SP Wank, SA Waschek, JA AF Harmar, AJ Arimura, A Gozes, I Journot, L Laburthe, M Pisegna, JR Rawlings, SR Robberecht, P Said, SI Sreedharan, SP Wank, SA Waschek, JA TI International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide SO PHARMACOLOGICAL REVIEWS LA English DT Review ID DIFFERENTIAL SIGNAL-TRANSDUCTION; IN-SITU HYBRIDIZATION; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; PACAP RECEPTOR; MESSENGER-RNA; SPLICE VARIANTS; BINDING-SITES; VIP RECEPTOR; RAT-BRAIN C1 Royal Edinburgh & Associated Hosp, MRC, Brain Metab Unit, Edinburgh, Midlothian, Scotland. Tulane Univ, Med Ctr, US Japan Biomed Res Labs, Belle Chasse, LA USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, Ramat Aviv, Israel. CCIPE, CNRS, UPR 9023, F-34094 Montpellier, France. Univ Paris 07, INSERM, U410, Paris, France. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, UCAL DDRC, CURE VA, Los Angeles, CA USA. Life Sci Resources, Cambridge, England. Free Univ Brussels, Lab Chim Biol & Nutr, Brussels, Belgium. SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. Univ Calif San Francisco, Dept Med, Div Allergy & Immunol, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA. NIDDK, Digest Dis Branch, NIH, Bethesda, MD USA. RP Univ Edinburgh, Dept Pharmacol, MRC, Brain Metab Unit, 1 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland. EM Tony.Harmar@ed.ac.uk RI LABURTHE, Marc/C-1875-2012; OI Harmar, Anthony/0000-0002-3838-9264 NR 82 TC 613 Z9 630 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 EI 1521-0081 J9 PHARMACOL REV JI Pharmacol. Rev. PD JUN PY 1998 VL 50 IS 2 BP 265 EP 270 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZW733 UT WOS:000074442300003 PM 9647867 ER PT J AU Finkelstein, RR Wang, ML Lynch, TJ Rao, S Goodman, HM AF Finkelstein, RR Wang, ML Lynch, TJ Rao, S Goodman, HM TI The Arabidopsis abscisic acid response locus ABI4 encodes an APETALA2 domain protein SO PLANT CELL LA English DT Article ID DNA-BINDING PROTEINS; SEED DEVELOPMENT; POSTTRANSCRIPTIONAL REGULATION; SIGNAL-TRANSDUCTION; DISEASE RESISTANCE; MESSENGER-RNA; GENE; THALIANA; EXPRESSION; ABA AB Arabidopsis abscisic acid (ABA)-insensitive abi4 mutants have pleiotropic defects in seed development, including decreased sensitivity to ABA inhibition of germination and altered seed-specific gene expression. This phenotype is consistent with a role for ABI4 in regulating seed responses to ABA and/or seed-specific signals. We isolated the ABI4 gene by positional cloning and confirmed its identity by complementation analysis. The predicted protein product shows homology to a: plant-specific family of transcriptional regulators characterized by a conserved DNA binding domain, the APETALA2 domain. The single mutant allele identified has a single base pair deletion, resulting in a frameshift that should disrupt the C-terminal half of the protein but leave the presumed DNA binding domain intact. Expression analyses showed that despite the seed-specific nature of the mutant phenotype, ABI4 expression is not seed specific. C1 Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Finkelstein, RR (reprint author), Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. EM finkelst@lifesci.lscf.ucsb.edu NR 68 TC 382 Z9 399 U1 2 U2 29 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD JUN PY 1998 VL 10 IS 6 BP 1043 EP 1054 DI 10.1105/tpc.12.4.599 PG 12 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA ZX908 UT WOS:000074567500016 PM 9634591 ER PT J AU King, DW Leskin, GA King, LA Weathers, FW AF King, DW Leskin, GA King, LA Weathers, FW TI Confirmatory factor analysis of the Clinician-Administered PTSD Scale: Evidence for the dimensionality of posttraumatic stress disorder SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID INTRUSION; INDEXES AB The Clinician-Administered PTSD Scale (CAPS; Blake et al., 1990) is a structured interview that assesses the 17 key symptoms of posttraumatic stress disorder (PTSD) as established in the Diagnostic and Statistical Manual of Menial Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994). CAPS data from 524 treatment-seeking male military veterans were submitted to confirmatory factor analysis to test a series of nested models reflecting alternative representations of PTSD dimensionality: (a) a 4-factor, 1st-order solution; (b) a 2-factor, higher order solution; (c) a single-factor, higher order solution; and (d) a single-factor, Ist-order solution. The model of best fit was the 4-factor, Ist-order solution, containing moderately to highly correlated yet distinct Ist-order factors corresponding to the reexperiencing, effortful avoidance, emotional numbing, and hyperarousal aspects of PTSD. Implications for theory, assessment, and future research are presented in this article. C1 Boston Dept Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, Behav Sci Div 116B2, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston Dept Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, Boston, MA 02130 USA. Tufts Univ, Sch Med, Medford, MA 02155 USA. Auburn Univ, Dept Psychol, Auburn, AL 36849 USA. RP King, DW (reprint author), Boston Dept Vet Affairs Med Ctr, Natl Ctr Posttraumat Stress Disorder, Behav Sci Div 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. NR 31 TC 435 Z9 443 U1 6 U2 33 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD JUN PY 1998 VL 10 IS 2 BP 90 EP 96 DI 10.1037/1040-3590.10.2.90 PG 7 WC Psychology, Clinical SC Psychology GA ZW310 UT WOS:000074397400002 ER PT J AU Eisenthal, S Stoeckle, JD AF Eisenthal, S Stoeckle, JD TI Medical residents evaluate their medical school training in psychosocial care SO PSYCHOLOGICAL REPORTS LA English DT Article ID SKILLS AB A questionnaire was sent to all 77 general medical residents at one teaching hospital (18 primary care and 59 the traditional program), to investigate retrospectively their psychosocial training in medical school. 62 complete surveys (81%) were returned. The training was rated good by 62% of the residents and important for psychosocial practice by 45%. In ambulatory settings, supervisors were rated as supporting the doctor-patient relationship (79%) and spending rime on psychosocial problems (65%). In inpatient settings, spending lime on psychosocial problems was not widely supported (36%). Training to interview was rated far from optimal by 49% of the residents. Psychosocial attitudes in residency did not have substantial correlations with training. In the choice of residency program, what distinguished residents in primary care from those in the traditional program was the positive ratings given their supervisors' psychosocial orientation, but not the supervisors' nor the residents' psychosocial competency or weeks spent in training. In sum, the two most potent influences on psychosocial orientation appear to be positive role models and the clinical setting. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Eisenthal, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St, Boston, MA 02114 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU PSYCHOLOGICAL REPORTS PI MISSOULA PA P O BOX 9229, MISSOULA, MT 59807 USA SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD JUN PY 1998 VL 82 IS 3 BP 1375 EP 1386 PN 2 PG 12 WC Psychology, Multidisciplinary SC Psychology GA 106VP UT WOS:000075171400043 PM 9709539 ER PT J AU Hilsenroth, MJ Holdwick, DJ Castlebury, FD Blais, MA AF Hilsenroth, MJ Holdwick, DJ Castlebury, FD Blais, MA TI The effects of DSM-IV cluster B personality disorder symptoms on the termination and continuation of psychotherapy SO PSYCHOTHERAPY LA English DT Article ID COLLABORATIVE RESEARCH-PROGRAM; OBSESSIVE-COMPULSIVE DISORDER; AXIS-II DIAGNOSES; TERM FOLLOW-UP; BORDERLINE PERSONALITY; INTERPERSONAL PROBLEMS; MAJOR DEPRESSION; PANIC DISORDER; OUTPATIENT POPULATION; THERAPEUTIC-COMMUNITY AB This study investigates the relationship between therapy attendance with DSM-IV criteria for the cluster B personality disorders (antisocial [ANPD]; borderline [BPD]; histrionic [HPD]; and narcissistic [NPD]). Ninety patients who were found to meet DSM-IV criteria for an Axis II disorder (cluster A personality disorders = 10; ANPD = 20, BPD = 25, HPD = 5, NPD = 14; cluster C personality disorders = 16). Total number of DSM-IV criteria for BPD (r = .33, p = .001) and ANPD (r = -.22, p = .04) were significantly related to the number of psychotherapy sessions attended by a patient. Stepwise regression indicated that the 5 individual criteria BPD-1, NPD-4, BPD-8, HPD-8, and ANPD-7 (in order of entry into the regression equation) were independent and nonredundant predictors that explained 31% of variance found in the number of psychotherapy sessions attended by patients. The presence or absence of three of these individual criteria provided a good balance of positive predictive power (.78-.95) and overall correct classification rate (.53-.69) for therapy continuation. Clinical and research implications of personality characteristics are discussed in relation to the termination and continuation of psychotherapy. C1 Univ Arkansas, Dept Psychol, Fayetteville, AR 72701 USA. Univ Tennessee, Knoxville, TN 37996 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hilsenroth, MJ (reprint author), Univ Arkansas, Dept Psychol, 216 Mem Hall, Fayetteville, AR 72701 USA. EM hils@comp.uark.edu NR 87 TC 35 Z9 36 U1 5 U2 7 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI PHOENIX PA 3900 E CAMELBACK RD #200, PHOENIX, AZ 85018 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD SUM PY 1998 VL 35 IS 2 BP 163 EP 176 DI 10.1037/h0087845 PG 14 WC Psychology, Clinical SC Psychology GA 179KK UT WOS:000079325700003 ER PT J AU McLoud, TC AF McLoud, TC TI Should cutting needles replace needle aspiration of lung lesions? SO RADIOLOGY LA English DT Editorial Material DE biopsies, technology,; editorials; lung, biopsy,; lung neoplasms, diagnosis ID BIOPSY C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP McLoud, TC (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ-FND 216,POB 9657,55 Fruit St, Boston, MA 02114 USA. NR 10 TC 8 Z9 10 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1998 VL 207 IS 3 BP 569 EP 570 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZN534 UT WOS:000073655500004 PM 9609875 ER PT J AU Jaramillo, D Connolly, SA Mulkern, RV Shapiro, F AF Jaramillo, D Connolly, SA Mulkern, RV Shapiro, F TI Developing epiphysis: MR imaging characteristics and histologic correlation in the newborn lamb SO RADIOLOGY LA English DT Article DE bones, epiphyses; bones, growth and development; cartilage MR; knee; knee, anatomy; knee, MR ID BOVINE ARTICULAR-CARTILAGE; GROWTH PLATE; MAGNETIZATION-TRANSFER; HYALINE CARTILAGE; SIGNAL INTENSITY; IN-VIVO; SEQUENCES; APPEARANCE; AGE; OSTEOCHONDROSIS AB PURPOSE: To correlate magnetic resonance (MR) signal characteristics of developing regions at the end of bones with the histologic findings. MATERIALS AND METHODS: In 36 newborn lamb epiphyses (including cartilage of the epiphysis and physis, and bone of the secondary ossification center and juxtaphyseal metaphysis), signal intensity and thickness of cartilaginous regions seen on MR images were correlated with architecture and thickness of zones shown in corresponding histologic sections. Possible effects of T2, magnetization transfer, fat or water content, chemical shift, and anisotropy on differences in regional signal intensity were evaluated. RESULTS: MR imaging depicted five regions between the secondary ossification center and the metaphysis corresponding histologically to (a) zone of provisional calcification of the secondary ossification center, (b) physis of the secondary ossification center, (c) epiphyseal cartilage, (d) physis, and (e) zone of provisional calcification. The thickness of regions shown on T1- and T2-weighted images correlated with that of histologic zones (r = .9). T2 signal intensity and relaxation time were greater in physeal than in epiphyseal cartilage (P < .01). No regional differences due to fat or water content, magnetization transfer, chemical shift, or anisotropy were found. CONCLUSION: MR imaging findings differentiate epiphyseal and physeal regions and correlate with histologic findings. T2 is slower in physeal than in epiphyseal cartilage, probably reflecting differences in water binding. C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Jaramillo, D (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAMS NIH HHS [AR42396-02] NR 38 TC 39 Z9 45 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1998 VL 207 IS 3 BP 637 EP 645 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZN534 UT WOS:000073655500014 PM 9609885 ER PT J AU Stone, M AF Stone, M TI Encyclopedia of family health SO REFERENCE & USER SERVICES QUARTERLY LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Stone, M (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER LIBRARY ASSOC PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 USA SN 1094-9054 J9 REF USER SERV Q JI Ref. User Serv. Q. PD SUM PY 1998 VL 37 IS 4 BP 376 EP 376 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 176KF UT WOS:000079149700072 ER PT J AU Curry, MA Burton, D Fields, J AF Curry, MA Burton, D Fields, J TI The prenatal psychosocial profile: A research and clinical tool SO RESEARCH IN NURSING & HEALTH LA English DT Article DE psychosocial; pregnancy; psychometrics ID SOCIAL SUPPORT; PREGNANCY OUTCOMES; MATERNAL STRESS; BIRTH OUTCOMES; WOMEN; WEIGHT AB This report summarizes five studies of culturally diverse women who were administered the Prenatal Psychosocial Profile (PPP). These data from 3,444 rural and urban women of all childbearing ages support the validity and reliability of the PPP as a measure of stress, support from partner, and support from others. The self-esteem scale is a valid and reliable measure for Caucasian and African American women. However, the cultural appropriateness of the self-esteem scale for Native American women is questionable, and it is neither valid nor culturally appropriate for traditional Hispanic women. The mean scores for stress, partner support, and other support were similar for all groups except for scales expected to differ by sample groups. Thus, suggested cutoff scores should be useful for screening purposes. The PPP provides a brief, yet comprehensive profile that is accepted by participants and useful to researchers and clinicians. (C) 1998 John Wiley & Sons, Inc. C1 Oregon Hlth Sci Univ, Sch Nursing, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Curry, MA (reprint author), Oregon Hlth Sci Univ, Sch Nursing, 3181 Sam Jackson Pk Rd, Portland, OR 97201 USA. FU NINR NIH HHS [R01-NR02696-04, R01-NR02410-01]; PHS HHS [NIH 02686-01] NR 23 TC 59 Z9 59 U1 1 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD JUN PY 1998 VL 21 IS 3 BP 211 EP 219 DI 10.1002/(SICI)1098-240X(199806)21:3<211::AID-NUR4>3.0.CO;2-K PG 9 WC Nursing SC Nursing GA ZP766 UT WOS:000073786300004 PM 9609506 ER PT J AU Lalani, T Bhol, K Khan, IU Ahmed, AR AF Lalani, T Bhol, K Khan, IU Ahmed, AR TI The scarring processes in mucosal tissues after immune injury SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE fibrosis; autoimmune disorders; cutaneous; mucosa ID EPIDERMOLYSIS-BULLOSA-ACQUISITA; GROWTH-FACTOR-BETA; INTERCELLULAR-ADHESION MOLECULE-1; PORPHYRIA CUTANEA-TARDA; FAT-STORING CELLS; SYSTEMIC-SCLEROSIS; ENDOTHELIAL-CELLS; LOCALIZED SCLERODERMA; FIBROBLAST SUBPOPULATIONS; CONNECTIVE-TISSUE AB Objectives: An important feature of the healing processes is scar formation which may be necessary for organism survival. If it proceeds to the pathological state, it may impair normal function. The purpose of this review is to focus on some of the factors that may influence this process after immune injury, comparing it in the skin and mucosa. Methods: A detailed literature search of peer-reviewed journals was conducted. Studies reported in all languages considered relevant and important were used, including humans, animals, and tissue culture. Results: Analysis of the data indicate that the scarring process is mainly dependent on (1) the type of the lesion, (2) the cause and duration of injury, and (3) the tissue involved and its microenvironment. Equally important is the large spectrum and heterogenicity in the biological activity of fibroblasts and their role in scar formation. Conclusions: The process of scar formation is complex and multistep process and is affected and influenced by local and systemic factors. Although it appears irreversible, there are pharmacological agents available, and under investigation, that may minimize its detrimental effects. Copyright (C) 1998 by W.B. Saunders Company. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NEI NIH HHS [EYO 8379] NR 120 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD JUN PY 1998 VL 27 IS 6 BP 371 EP 381 DI 10.1016/S0049-0172(98)80017-6 PG 11 WC Rheumatology SC Rheumatology GA ZW869 UT WOS:000074456500005 PM 9662756 ER PT J AU Gabuzda, D He, JL Ohagen, A Vallat, AV AF Gabuzda, D He, JL Ohagen, A Vallat, AV TI Chemokine receptors in HIV-1 infection of the central nervous system SO SEMINARS IN IMMUNOLOGY LA English DT Review DE HIV-1; chemokine receptor; chemokines; microglia; brain ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-COUPLED RECEPTOR; BLOOD-BRAIN-BARRIER; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; POLYMERASE CHAIN-REACTION; CD4-INDEPENDENT INFECTION; MOLECULAR-CLONING; EOTAXIN RECEPTOR; FUSION COFACTOR; V3 LOOP AB Several members of the chemokine receptor are used as coreceptors for HIV-1 infection in the central nervous system (CNS). CCR5 and CCR3 are coreceptors together with CD4 for HIV-1 infection of microglia, the major target for HIV-1 infection in the CNS. Microglia express CXCR4, but their infection by HIV-1 viruses that use only CXCR4 as a coreceptor is relatively inefficient. CXCR4 is also expressed in subpopulations of neurons that are resistant to HIV-1 infection. Additional orphan chemokine receptors that can mediate HIV-1 or SIV entry are expressed in the brain or neurally-derived cell lines, but their role in CNS infection has not been defined. The pattern of chemokine receptor expression in the brain is likely to determine the tropism of HIV-1 for particular CNS target cells and to impact inflammatory and degenerative mechanisms associated with CNS infection. C1 Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Div Human Retrovirol, JF712,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI07386]; NINDS NIH HHS [NS35734] NR 105 TC 60 Z9 62 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD JUN PY 1998 VL 10 IS 3 BP 203 EP 213 DI 10.1006/smim.1998.0133 PG 11 WC Immunology SC Immunology GA 131NG UT WOS:000076581700006 PM 9653047 ER PT J AU Choe, H Martin, KA Farzan, M Sodroski, J Gerard, NP Gerard, C AF Choe, H Martin, KA Farzan, M Sodroski, J Gerard, NP Gerard, C TI Structural interactions between chemokine receptors, gp120 Env and CD4 SO SEMINARS IN IMMUNOLOGY LA English DT Review DE seven transmembrane segment receptors; viral infection; receptor binding; CCR5; CXCR4 ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 ENTRY; ENVELOPE GLYCOPROTEIN; CD4-POSITIVE CELLS; T-LYMPHOCYTES; AIDS VIRUS; INFECTION; CCR5; TYPE-1; CORECEPTOR AB Seven transmembrane segment (7TMS) receptors for chemokines and related molecules have been demonstrated to be essential, in addition to CD4, for HIV and SIV infection. The beta-chemokine receptor CCR5 is the primary, perhaps sole, co-receptor for HIV-1 during the early and chronic phases of infection and supports infection by most primary HIV-1 and many SN isolates. Late-stage primary and laboratory-adapted HIV-1, HIV-2, and SIV isolates can use other 7TMS receptors. CXCR4 appears especially important in late-stage HN infection; several related receptors can also be used. The specificity of SIV viruses is similar. Commonalities among these receptors, combined with analyses of mutated molecules, indicate that discrete, conformationally-dependent sites on the chemokine receptors determine their association with the third variable and conserved regions of viral envelope glycoproteins. These studies are useful for elucidating the mechanism and molecular determinants of HIV-1 entry, and of inhibitors to that entry. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Childrens Hosp, Ina Sue Perlmutter Lab, Boston, MA 02115 USA. Beth Israel Deaconess Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Hosp, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Choe, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol,Div Human Retrovirol, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL36162, HL51366]; NIAID NIH HHS [AI41581] NR 37 TC 45 Z9 46 U1 2 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD JUN PY 1998 VL 10 IS 3 BP 249 EP 257 DI 10.1006/smim.1998.0127 PG 9 WC Immunology SC Immunology GA 131NG UT WOS:000076581700010 PM 9653051 ER PT J AU O'Malley, ME Boland, GW Wood, BJ Mueller, PR AF O'Malley, ME Boland, GW Wood, BJ Mueller, PR TI Helical CT angiography of the peripancreatic vessels SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Review DE pancreas; CT; helical angiography; pancreatic cancer ID SPIRAL CT; PANCREATIC ADENOCARCINOMA; CLINICAL-APPLICATIONS; ABDOMEN; ARTERIOGRAPHY; DEPICTION; DIAGNOSIS; TUMORS; CANCER AB Helical computer tomography (CT) scanning allows for acquisition of a volume of data in a relatively short period of time. When data acquisition is timed to peak vascular enhancement, postprocessing of the data can be performed to optimally display vascular anatomy. This CT scanning technique is known as CT angiography (CTA). This article reviews the fundamentals of helical CTA and it's application to the peripancreatic vessels. Emphasis is placed on the role of helical CTA in patients with pancreatic cancer. C1 Massachusetts Gen Hosp, Dept Radiol, Abdominal Imaging & Intervent Radiol Div, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Abdominal Imaging & Intervent Radiol Div, 32 Fruit St, Boston, MA 02114 USA. NR 28 TC 1 Z9 1 U1 1 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PD JUN PY 1998 VL 15 IS 2 BP 113 EP 121 DI 10.1055/s-2008-1057040 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 172RU UT WOS:000078938700003 ER PT J AU Graybill, JR AF Graybill, JR TI Itraconazole: Managing mycotic complications in immunocompromised patients SO SEMINARS IN ONCOLOGY LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MULTIPLE-DOSE PHARMACOKINETICS; BONE-MARROW TRANSPLANTATION; INVASIVE ASPERGILLOSIS; AMPHOTERICIN-B; FUNGAL-INFECTIONS; ORAL SOLUTION; FLUCONAZOLE; THERAPY; HISTOPLASMOSIS C1 Univ Texas, Hlth Sci Ctr, Audie L Murphy Vet Hosp, Infect Dis Sect 111F, San Antonio, TX 78284 USA. RP Graybill, JR (reprint author), Univ Texas, Hlth Sci Ctr, Audie L Murphy Vet Hosp, Infect Dis Sect 111F, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 54 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 1998 VL 25 IS 3 SU 7 BP 58 EP 63 PG 6 WC Oncology SC Oncology GA ZZ831 UT WOS:000074771500013 PM 9671333 ER PT J AU Tan, G Monga, U Thornby, J Monga, T AF Tan, G Monga, U Thornby, J Monga, T TI Sexual functioning, age, and depression revisited SO SEXUALITY AND DISABILITY LA English DT Article ID PARKINSONS-DISEASE; DYSFUNCTION; IMPOTENCE; CANCER; MEN C1 VA Med Ctr, Radiotherapy Serv, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Phys Med & Rehabil Serv, Houston, TX USA. VA Med Ctr, Psychol Serv, Houston, TX USA. RP Tan, G (reprint author), Vet Affairs Med Ctr, Psychiat Serv 116B, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 27 TC 8 Z9 8 U1 1 U2 3 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD SUM PY 1998 VL 16 IS 2 BP 77 EP 86 DI 10.1023/A:1023023924804 PG 10 WC Rehabilitation SC Rehabilitation GA ZV979 UT WOS:000074361500002 ER PT J AU Nelles, G Cramer, SC Schaechter, JD Kaplan, JD Finklestein, SP AF Nelles, G Cramer, SC Schaechter, JD Kaplan, JD Finklestein, SP TI Quantitative assessment of mirror movements after stroke SO STROKE LA English DT Article; Proceedings Paper CT 23rd International Joint Conference on Stroke and Cerebral Circulation CY FEB 05-07, 1998 CL ORLANDO, FLORIDA DE dynamometer, computerized; mirror movements; motor activity; stroke, outcome ID HEMIPLEGIC CEREBRAL-PALSY; CENTRAL MOTOR PATHWAYS; CORTEX; REORGANIZATION; HEMIPARESIS; INFARCTION; HANDEDNESS; CHILDREN; PATTERNS; LESIONS AB Background and Purpose-Mirror movements (MM) are involuntary synchronous movements of one limb during voluntary unilateral movements of the opposite limb. We measured MM in stroke and control subjects and evaluated whether MM after stroke are related to motor function. Methods-Twenty-three patients and 16 control subjects were studied. A computerized dynamometer was used during two squeezing tasks to measure intended movements from the active hand as well as MM from the opposite hand. Motor deficits were measured with the arm motor component of the Fugl-Meyer scale. Results-During paretic hand squeezing, MM in the unaffected hand were detected in 70% (repetitive squeeze) to 78% (sustained squeeze) of stroke patients. For both tasks, this was significantly (P<0.05) greater than the incidence of MM in the paretic hand or in either hand of control subjects (17% to 44%), except when compared with the incidence of MM in the dominant hand of control subjects (56%; P=0.17), The incidence of MM in the paretic hand was not significantly different from that seen in either hand of control subjects. Patients with MM in the unaffected hand had significantly greater motor deficit than patients without MM. Patients with MM in the paretic hand had significantly better motor function than patients without MM. Conclusions-Simultaneously recording motor performances of both hands provides precise information to characterize MM, MM in the unaffected hand and in the paretic hand are associated with different degrees of motor deficit after stroke. Evaluation of MM may be useful for studying mechanisms of stroke recovery. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. Northeastern Univ, Bouve Coll Pharm & Hlth Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp Spaulding, NeuroRecovery Program, Boston, MA USA. Harvard Mit Div Hlth Sci & Technol, Clin Investigator Training Program, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Nelles, G (reprint author), Univ Essen Gesamthsch, Philippusstift & Neurol Klin, Neurol Therapiezentrum, Laarmannstr 14, D-45359 Essen, Germany. EM gereon.nelles@uni-essen.de NR 35 TC 74 Z9 76 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 1998 VL 29 IS 6 BP 1182 EP 1187 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZR468 UT WOS:000073979900017 PM 9626292 ER PT J AU Madras, BK Meltzer, PC Liang, AY Elmaleh, DR Babich, J Fischman, AJ AF Madras, BK Meltzer, PC Liang, AY Elmaleh, DR Babich, J Fischman, AJ TI Altropane, a SPECT or PET imaging probe for dopamine neurons: I. Dopamine transporter binding in primate brain SO SYNAPSE LA English DT Article DE dopamine transporter; dopamine neurons; Parkinson's disease; cocaine; WIN 35,428; aging; SPECT imaging; PET imaging ID COCAINE RECOGNITION SITES; POSITRON EMISSION TOMOGRAPHY; CFT WIN 35,428; PARKINSONS-DISEASE; HIGH-AFFINITY; MONKEY BRAIN; H-3 CFT; NONHUMAN-PRIMATES; I-125 RTI-55; BETA-CIT AB Increasing evidence suggests that the dopamine transporter is an important marker for physiological and pathological changes in dopamine neurons. Potent dopamine transport inhibitors of the phenyltropane series (e.g., WIN 35,428 or CFT) are particularly suitable for PET (positron emission tomography) or SPECT (single photon emission computed tomography) imaging of the dopamine transporter in living brain. We investigated whether altropane, an N-iodoallyl analog of WIN 35,428 (IACFT:E-N-iodoallyl-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane), displayed in vitro properties suitable for evaluation as a SPECT imaging agent. In brain striatum of cynomolgus monkey (Macaca fascicularis), the unlabeled E-isomer (IC50: 6.62 +/- 0.78 nM) was more potent than the Z-isomer (IC50: 52.6 +/- 0.3 mM) and displayed a relatively high dopamine:serotonin transporter selectivity (28-fold). In radiolabeled form, [I-125]altropane bound to sites in the striatum with a single high affinity (K-D: 5.33 +/- 0.55 nM) and with a site density (B-MAX: 301 pmol/g original wet tissue weight) that was within the density range reported previously for the dopamine transporter in striatum. Drugs inhibited [I-125] altropane binding with a rank order of potency that corresponded closely to their potencies for inhibiting [H-3]WIN 35,428 binding (r(2): 0.99; P < 0.0001) to the blocking dopamine transport. The favorable binding properties of altropane, together with its rapid entry into primate brain and highly localized distribution in dopamine-rich brain regions, suggest it is a suitable iodinated probe for monitoring the dopamine transporter in vitro and in vivo by SPECT or PET imaging. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Psychiat, Southborough, MA 01772 USA. Organix Inc, Woburn, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Madras, BK (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Psychiat, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM bmadras@warren.med.harvard.edu FU NIDA NIH HHS [DA06303, DA09462]; NINDS NIH HHS [NS30556] NR 73 TC 30 Z9 32 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUN PY 1998 VL 29 IS 2 BP 93 EP 104 DI 10.1002/(SICI)1098-2396(199806)29:2<93::AID-SYN1>3.0.CO;2-5 PG 12 WC Neurosciences SC Neurosciences & Neurology GA ZK687 UT WOS:000073351100001 PM 9593100 ER PT J AU Madras, BK Gracz, LM Meltzer, PC Liang, AY Elmaleh, DR Kaufman, MJ Fischman, AJ AF Madras, BK Gracz, LM Meltzer, PC Liang, AY Elmaleh, DR Kaufman, MJ Fischman, AJ TI Altropane, a SPECT or PET imaging probe for dopamine neurons: II. distribution to dopamine-rich regions of primate brain SO SYNAPSE LA English DT Article DE dopamine transporter; dopamine neurons; Parkinson's disease; cocaine; WIN 35,428; aging; SPECT imaging; PET imaging; neurodegenerative diseases ID COCAINE RECOGNITION SITES; C-11 BETA-CIT; HIGH-AFFINITY; IN-VIVO; PARKINSONS-DISEASE; I-125 RTI-55; SEROTONIN TRANSPORTERS; NUCLEUS-ACCUMBENS; MONKEY BRAIN; RAT-BRAIN AB The dopamine transporter in brain, localized almost exclusively on dopamine neurons, is an effective window on dopamine neurons. SPECT or PET imaging of the transporter in brain requires selective imaging agents that display appropriate pharmacokinetic properties. We previously reported that [I-125]altropane ([I-125]IACFT,2 beta-carbomethoxy-3 beta-(4-fluoraphenyl)-n-(1-iodoprop-1-en-3-yl)nortropane) bound with high affinity (Kd: 5.33 nM) to a single site on the dopamine transporter and was selective for dopamine over the serotonin transporter in homogenates of monkey striatum. To determine whether the selective binding of [I-125]altropane is reflected in its brain distribution, the in vitro and ex vivo distribution of [I-125]altropane in squirrel monkey (Saimiri sciureus) brain was determined by quantitative autoradiography of coronal. brain sections. In vitro, [I-125]altropane (2 nM) distribution was discrete and was detectable primarily in the dopamine-rich putamen, caudate nucleus, and nucleus accumbens. The resulting putamen:cerebellum ratio exceeded 120:1 (n = 3). The selective in vitro binding of [I-125]altropane to the dopamine transporter, at concentrations approaching its Kd value (Kd: 5.33 nM, a single high affinity site), highlight its suitability for investigating the density of the dopamine transporter in various brain regions in vitro. Ex vivo autoradiography was conducted in monkeys to determine whether the brain distribution of [I-125]altropane in vitro was predictive of its brain distribution pattern after intravenous administration. Thirty minutes after intravenous injection, highest levels of [I-125]altropane (0.3 nmol/kg) were detected in the caudate-putamen and nucleus accumbens and lowest levels in the cerebellum and cortex. The putamen or caudate:cerebellum ratio was ?. SPECT imaging of the brain within 30 min of i.v. injection confirmed the rapid and selective accumulation of [I-123]altropane to the striatum. The selective binding of altropane to the dopamine-rich striatum within 30 min of i.v. administration indicates that it is uniquely suited for SPECT or PET imaging of the dopamine transporter and associated dopamine neurons. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Psychiat, Southborough, MA 01772 USA. Organix Inc, Woburn, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Madras, BK (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Psychiat, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM bmadras@warren.med.harvard.edu FU NIDA NIH HHS [DA09462, DA06303]; NINDS NIH HHS [NS30556] NR 60 TC 34 Z9 35 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUN PY 1998 VL 29 IS 2 BP 105 EP 115 DI 10.1002/(SICI)1098-2396(199806)29:2<105::AID-SYN2>3.0.CO;2-B PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZK687 UT WOS:000073351100002 PM 9593101 ER PT J AU Madras, BK Gracz, LM Fahey, MA Elmaleh, D Meltzer, PC Liang, AY Stopa, EG Babich, J Fischman, AJ AF Madras, BK Gracz, LM Fahey, MA Elmaleh, D Meltzer, PC Liang, AY Stopa, EG Babich, J Fischman, AJ TI Altropane, a SPECT or PET imaging probe for dopamine neurons: III. Human dopamine transporter in postmortem normal and Parkinson's diseased brain SO SYNAPSE LA English DT Article DE dopamine transporter; SPECT imaging; dopamine neurons; Parkinson's disease; cocaine; neurodegenerative diseases ID COCAINE RECOGNITION SITES; CFT WIN 35,428; HIGH-AFFINITY; MONKEY BRAIN; BETA-CIT; H-3 CFT; BINDING-SITES; IN-VIVO; SEROTONIN TRANSPORTERS; CAUDATE-NUCLEUS AB Increasing evidence suggests that the dopamine transporter is situated almost exclusively on dopamine neurons. Accordingly, it is an valuable marker for Parkinson's disease and other pathological states of dopamine neurons. We previously demonstrated that the potent dopamine transport inhibitor [I-125]altropane (IACFT:E-N-iodoallyl-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane) is a high affinity selective probe for the dopamine transporter in monkey brain and an effective SPECT imaging agent in nonhuman primate brain. We now report the binding properties of [I-125]altropane in postmortem tissue of normal human brain and compare the findings to Parkinson's diseased brain. In homogenates of human brain putamen, [I-125]altropane bound with high affinity (K-D: 4.96 +/- 0.38 nM, n = 4) and site density (B-MAX: 212 +/- 41.1 pmol/g original wet tissue weight) well within the density range reported previously for the dopamine transporter in this brain region. Drugs inhibited [I-125]altropane binding with a rank order of potency that corresponded closely to their rank order for blocking dopamine transport (r 0.98, P < 0.001). In postmortem Parkinson's diseased brain, bound [I-125]altropane (1 nM) was markedly reduced (89%, 99% in putamen, depending on measures of nonspecific binding) compared with normal aged-matched controls (normal putamen: 49.2 +/- 8.1 pmol/g; Parkinson's diseased putamen: 0.48 +/- 0.33 pmol/g; n = 4). In vitro autoradiography, conducted in tissue sections at a single plane of the basal ganglia, revealed high levels of [I-125]altropane binding the caudate nucleus and putamen, but lower levels (73% of the caudate-putamen) in the nucleus accumbens (n = 7). In Parkinson's diseased brains (n = 4), [I-125]altropane binding was 13% of the levels detected in normal putamen, 17% of normal values in the caudate nucleus, and 25% of normal levels in nucleus accumbens. The association of [I-125]altropane to the dopamine transporter in human postmortem tissue, the marked reduction of [I-125]altropane binding in Parkinson's diseased brains, its rapid entry into brain and highly localized distribution in dopamine-rich brain regions, support its use as a probe for monitoring the dopamine transporter in vitro and in vivo by SPECT imaging. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Psychiat, Southborough, MA 01772 USA. Organix Inc, Woburn, MA USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Madras, BK (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Psychiat, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM bmadras@warren.med.harvard.edu FU NIDA NIH HHS [DA00304, DA06303]; NINDS NIH HHS [NS30556] NR 68 TC 49 Z9 51 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUN PY 1998 VL 29 IS 2 BP 116 EP 127 DI 10.1002/(SICI)1098-2396(199806)29:2<116::AID-SYN3>3.0.CO;2-A PG 12 WC Neurosciences SC Neurosciences & Neurology GA ZK687 UT WOS:000073351100003 PM 9593102 ER PT J AU Fischman, AJ Bonab, AA Babich, JW Palmer, EP Alpert, NM Elmaleh, DR Callahan, RJ Barrow, SA Graham, W Meltzer, PC Hanson, RN Madras, BK AF Fischman, AJ Bonab, AA Babich, JW Palmer, EP Alpert, NM Elmaleh, DR Callahan, RJ Barrow, SA Graham, W Meltzer, PC Hanson, RN Madras, BK TI Rapid detection of Parkinson's disease by SPECT with altropane: A selective ligand for dopamine transporters SO SYNAPSE LA English DT Article DE dopamine transporter; dopamine neurons; Parkinson's disease; movement disorders; cocaine; neurodegenerative diseases; SPECT imaging; PET imaging; aging; WIN 35,428 ID POSITRON EMISSION TOMOGRAPHY; COCAINE RECOGNITION SITES; I-123 BETA-CIT; MONOAMINE REUPTAKE SITES; BRAIN TRANSFER CONSTANTS; HEALTHY-HUMAN SUBJECTS; TIME UPTAKE DATA; GRAPHICAL EVALUATION; PRIMATE BRAIN; C-11 CFT AB Increasing evidence indicates that dopamine (DA) transporter density declines in Parkinson's disease (PD). 2 beta-Carbomethoxy-3 beta-(4-fluorophenyl)-n-(1-iodoprop-1-en-3-yl) nortropane (IACFT, Altropane(TM)) is a cocaine analog with high affinity and selectivity for dopamine transporter (DAT) sites in the striatum. In this study, single photon emission computed tomography (SPECT) with [I-123]altropane was used to measure DAT density in seven healthy volunteers (five males, age 37-75, and two females, ages 26 and 39) and eight male patients with Parkinson's disease (age 14-79, Hoehn and Yahr stage: 1.5-3 (n = 5) and 4-5 (n = 3)). Dynamic SPECT images and arterial blood samples were acquired over 1.5-2 hr and plasma radioactivity was analyzed chromatographically to obtain metabolite corrected arterial input functions. Binding potential (BP, B'(max)/K-D) for striatal (Str) DAT sites was calculated by two methods using occipital cortex (Occ) as a reference. In the first method, tissue time-activity curves (TAC) and metabolite corrected arterial input functions were analyzed by a linear graphical method developed for reversible receptor ligands. In the second method, the expression(Str(TAC) - Occ(TAC)) was fitted to a gamma variate function and the maximum divided by Occ(TAC) at the same time was used to estimate BP. In five of the PD patients, the SPECT data were compared with the results of PET with [F-18] B-fluoro DOPA (FD-PET). Plasma analysis indicated that [I-123]altropane is rapidly converted to polar metabolites. SPECT images in healthy volunteers showed that [I-123] altropane accumulated rapidly and selectively in the striatum and yielded excellent quality images within 1 h after injection. Both methods of analysis revealed a 7.6%/decade reduction in BP and average striatal values (corrected to age 25) were 1.83 +/- 0.22 and 2.09 +/- 0.20 by methods 1 and 2. In all the PD patients, striatal accumulation was markedly reduced and the pattern of loss was similar to that reported for DA; most profound in the posterior putamen with relative sparing of the caudate nuclei. A comparable pattern was observed with ED-PET For total striatum, age-corrected BP was significantly (P < 0.001) reduced; 0.83 +/- 0.06 (method 1), 0.84 +/- 0.07 (method 2). BPs measured by the two methods were remarkably similar and highly correlated r(2) = 0.88,(P < 0.001). These results indicate that [I-123]altropane is an excellent SPECT ligand for imaging the DAT/DA neurons in human brain. The high selectivity and rapid striatal accumulation of the ligand allows for accurate quantitation of DAT sites in less than 2 hr. The results further demonstrate that [I-123]altropane is an effective marker for PD. (C) 1998 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Lahey Clin, Dept Neurol, Burlington, MA USA. Organix Inc, Boston, MA USA. Northeastern Univ, Dept Chem, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 32 Fruit St, Boston, MA 02114 USA. EM fischman@petw6.mgh.harvard.edu FU NIDA NIH HHS [DA86303]; NINDS NIH HHS [NS30556] NR 54 TC 96 Z9 98 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUN PY 1998 VL 29 IS 2 BP 128 EP 141 DI 10.1002/(SICI)1098-2396(199806)29:2<128::AID-SYN4>3.0.CO;2-9 PG 14 WC Neurosciences SC Neurosciences & Neurology GA ZK687 UT WOS:000073351100004 PM 9593103 ER PT J AU Chen, DF Seibert, I Chen, HY Herbst-Kiene, I Pastucha, LT Stangel, W AF Chen, DF Seibert, I Chen, HY Herbst-Kiene, I Pastucha, LT Stangel, W TI Improvement of HLA class I and class II PCR-SSP typing by using timed-release activity of DNA polymerase SO TISSUE ANTIGENS LA English DT Article DE HLA typing; hot start PCR; PCR-SSP; timed-release activity of DNA polymerase AB Variable amounts of non-specific amplification may occur in HLA PCR-SSP typing, and this can be significantly reduced by the use of AmpliTaq Gold. Tn an effort to achieve an optimal balance between specificity and efficiency of the PCR amplification for both HLA alleles and the internal control, we designed a system of timed-release activity by combining two different Tao DNA polymerases. The reaction was started at a relatively low level of enzyme activity and as thermal cycling progressed more and more Ampli-Taq Gold was slowly activated for the reaction to continue. We applied this system to ail routine HLA PCR-SSP typing. The number of repeat typings due to non-specific amplification and/or amplification failure of the internal control was remarkably reduced. C1 Hannover Med Univ, Dept Bloodbank Immunohematol & Transfus Med, Hannover, Germany. RP Chen, DF (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, HLA CBRL, 800 Huntington Ave, Boston, MA 02115 USA. NR 4 TC 1 Z9 2 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUN PY 1998 VL 51 IS 6 BP 645 EP 648 DI 10.1111/j.1399-0039.1998.tb03007.x PG 4 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA ZY723 UT WOS:000074652900008 PM 9694357 ER PT J AU Churchill, WH McGurk, S Chapman, RH Wallace, EL Bertholf, MF Goodnough, LT Kao, KJ Olson, JD Woodson, RD Surgenor, DM AF Churchill, WH McGurk, S Chapman, RH Wallace, EL Bertholf, MF Goodnough, LT Kao, KJ Olson, JD Woodson, RD Surgenor, DM TI The Collaborative Hospital Transfusion Study: variations in use of autologous blood account for hospital differences in red cell use during primary hip and knee surgery SO TRANSFUSION LA English DT Article ID COST-EFFECTIVENESS; ALLOGENEIC TRANSFUSION; CONTROVERSIES; REPLACEMENT; MEDICINE AB BACKGROUND: Red cell use in patients undergoing Diagnosis Related Group (DRG) 209 procedures (major joint and limb reconstruction procedures of the lower extremities) has been shown to have large, unexplained interhospital variations. STUDY DESIGN AND METHODS: Abstracted records of 2590 consecutive DRG 209 patients at five university hospitals from January 1992 to December 1993 were stratified by procedure and preoperative blood deposit status. Patient characteristics and transfusion and in-hospital outcomes were compared across hospitals. RESULTS: Blood use among patients who did not preoperatively deposit blood was similar across hospitals. Significant differences were found across hospitals for total hip replacement patients in the percentage of patients preoperatively depositing blood (59-80%), percentage of patients receiving transfusion(s) (51 to >99%), the mean number of units collected per patient (1.6-2.9), and the mean number of unused autologous units per 100 patients (1-185). No significant differences were found in the percentage of those who deposited blood and then required allogeneic units. There was little variability in length of hospital stay or in last hematocrits. Findings were similar for total knee replacement patients. CONCLUSIONS: Interhospital variations in red cell use for primary total hip and knee reconstruction are primarily due to hospital-specific differences in autologous blood collection and transfusion. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Ctr Management Syst, Snowmass Village, CO USA. Univ Florida, Shands Hosp, Dept Pathol & Lab Med, Gainesville, FL USA. Barnes Hosp, Div Lab Med, St Louis, MO 63110 USA. Univ Iowa Hosp & Clin, Dept Pathol, Iowa City, IA 52242 USA. Univ Wisconsin Hosp, Hematol Sect, Madison, WI 53792 USA. RP Churchill, WH (reprint author), Brigham & Womens Hosp, Blood Bank, Div Clin Labs, Div Hematol Oncol, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-33774] NR 21 TC 25 Z9 26 U1 1 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 1998 VL 38 IS 6 BP 530 EP 539 DI 10.1046/j.1537-2995.1998.38698326332.x PG 10 WC Hematology SC Hematology GA ZX852 UT WOS:000074561900003 PM 9661686 ER PT J AU Kunschak, M Engl, W Maritsch, F Rosen, FS Eder, G Zerlauth, G Schwarz, HP AF Kunschak, M Engl, W Maritsch, F Rosen, FS Eder, G Zerlauth, G Schwarz, HP TI A randomized, controlled trial to study the efficacy and safety of C1 inhibitor concentrate in treating hereditary angioedema SO TRANSFUSION LA English DT Article ID C1-INHIBITOR; THERAPY AB BACKGROUND: No effective treatment exists in the United Stales for acute attacks of hereditary angioedema (HAE). STUDY DESIGN AND METHODS: To evaluate the efficacy and safety of C1 inhibitor concentrate in treating HAE, a large primary care and referral center hospital conducted a randomized, placebo-controlled, double-blind trial with intent-to-treat analysis. Of the 36 patients enrolled in the study, 23 received treatment, and 22 completed the trial. C1 inhibitor concentrate or albumin (placebo) infusions were administered in a blind fashion to HAE patients who came to the hospital for treatment no later than 5 hours after an attack began. RESULTS: Relief was almost twice as fast in persons receiving C1 inhibitor concentrate than in the controls: 7.62 hours (mean; SD 7.08) versus 15.35 hours (mean; SD 8.31), respectively. The difference for time-to-relief was highly significant (p = 0.007, Mann-Whitney U test). The median time-to-relief was 6.17 hours (interquartile range 0.33-15.35) in the treatment, group and 15.35 hours (interquartile range 14.00-22.83) in the control group. Resolution of symptoms was one-third faster in the C1 inhibitor concentrate group than in the placebo group: 23.98 hours (mean; SO 14.81) and 34.58 hours (mean; SD 13.56), respectively (p = 0.09, Mann-Whitney U test). Recovery of functional C1 inhibitor was 119.65 percent (mean; SD 50.80), and half-life was 37.87 hours (mean; SD 19.75). Recovery of antigenic C1 inhibitor was 147.75 percent (mean; SD 97.68), and half-life was 24.01 hours (mean; SD 9.70).There were no viral infections or serious adverse effects from the drug after 70 attacks in the treatment group and 96 attacks in the control group. CONCLUSIONS: C1 inhibitor concentrate is a safe, effective treatment for acute attacks of HAE. C1 Immuno AG, Res & Dev, A-1221 Vienna, Austria. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Immunol, Ctr Blood Res, Boston, MA 02115 USA. RP Schwarz, HP (reprint author), Immuno AG, Res & Dev, Ind Str 67, A-1221 Vienna, Austria. FU FDA HHS [FD-R-000659]; NCRR NIH HHS [RR-02172] NR 21 TC 112 Z9 114 U1 0 U2 3 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 1998 VL 38 IS 6 BP 540 EP 549 DI 10.1046/j.1537-2995.1998.38698326333.x PG 10 WC Hematology SC Hematology GA ZX852 UT WOS:000074561900004 PM 9661687 ER PT J AU Gonzalez, CH Marques-Dias, MJ Kim, CA Sugayama, SMM Da Paz, JA Huson, SM Holmes, LB AF Gonzalez, CH Marques-Dias, MJ Kim, CA Sugayama, SMM Da Paz, JA Huson, SM Holmes, LB TI Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy SO LANCET LA English DT Article ID PARAPLEGIA; ABORTION; SEQUENCE AB Background Misoprostol is commonly used to induce abortion in Brazil, and in other countries in South and Central America where abortions are illegal. However, misoprostol is not very effective in inducing abortions, and exposure to the drug in utero can cause abnormalities in the fetus. We aimed to define the common phenotypical effects of exposure to the drug. Methods We studied 42 infants from Sao Paulo, Brazil, who were exposed to misoprostol during the first 3 months of gestation, and then born with congenital abnormalities. We interviewed each of the infants' mothers to find out about misoprostol exposure and dosage. Each infant was physically examined by a geneticist or a neuropaediatrician. Findings 17 of the infants had equinovarus with cranial-nerve defects. Ten children had equinovarus as part of more extensive arthrogryposis. The most distinctive phenotypes were arthrogryposis confined to the legs (five cases) and terminal transverse-limb defects (nine cases) with or without Mobius sequence. The most common dose of misoprostol taken was 800 mu g (range 200-16 000 mu g). Interpretation Deformities attributed to vascular disruption were found in these children. We suggest that the uterine contractions induced by misoprostol cause vascular disruption in the fetus, including brain-stem ischaemia. Information on the effects of taking misoprostol during pregnancy should be made more widely available, to dissuade women from misusing the drug. C1 Massachusetts Gen Hosp, Genet & Teratol Univ, Boston, MA 02115 USA. Univ Sao Paulo, Fac Med, Inst Crianca, Sao Paulo, Brazil. Oxford Radcliffe Hosp, Dept Clin Genet, Oxford, England. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Univ, Warren 801,55 Fruit St, Boston, MA 02115 USA. FU NICHD NIH HHS [R0I HD 33222] NR 24 TC 131 Z9 144 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 30 PY 1998 VL 351 IS 9116 BP 1624 EP 1627 DI 10.1016/S0140-6736(97)12363-7 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA ZR900 UT WOS:000074026600010 PM 9620717 ER PT J AU Moradpour, D Wakita, T Wands, JR Blum, HE AF Moradpour, D Wakita, T Wands, JR Blum, HE TI Tightly regulated expression of the entire hepatitis C virus structural region in continuous human cell lines SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CORE PROTEIN; TRANS-SUPPRESSION; GENE-EXPRESSION; REPLICATION; GENOME; HEPATOCYTES; SELECTION AB Investigation of the hepatitis C virus (HCV) life cycle is limited by the lack of an efficient cell culture system. Employing a tetracycline-regulated gene expression system we generated a panel of continuous human cell lines allowing the inducible expression and faithful processing of HCV structural proteins as well as of a functional NS2-3 autoprotease. HCV proteins were found in the cytoplasm in a pattern characteristic for the endoplasmic reticulum. High-level expression of HCV proteins was found to be cytotoxic. These cell lines represent a unique in vitro system in which to further investigate the structural proteins of HCV and to evaluate novel antiviral strategies against hepatitis C in a well-defined and reproducible cellular context. (C) 1998 Academic Press. C1 Univ Freiburg, Dept Med 2, D-79106 Freiburg, Germany. Tokyo Metropolitan Inst Med Sci, Dept Microbiol, Tokyo 113, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Canc Ctr,Mol Hepatol Lab, Boston, MA 02129 USA. RP Blum, HE (reprint author), Univ Hosp Freiburg, Dept Med 2, Hugstetter Str 55, D-79106 Freiburg, Germany. NR 24 TC 29 Z9 29 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 29 PY 1998 VL 246 IS 3 BP 920 EP 924 DI 10.1006/bbrc.1998.8727 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZT218 UT WOS:000074061900062 PM 9618312 ER PT J AU Neville, CM Choe, YH Lee, YS Spinner, D Tsay, HJ Schmidt, J AF Neville, CM Choe, YH Lee, YS Spinner, D Tsay, HJ Schmidt, J TI The E protein CTP4 and acetylcholine receptor expression in development and denervation supersensitivity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOOP-HELIX PROTEINS; DIRECT GENE-TRANSFER; DNA-BINDING; ELECTRICAL-ACTIVITY; SKELETAL-MUSCLE; TRANSCRIPTIONAL-ACTIVATION; MESSENGER-RNA; SUBUNIT GENE; MYOGENIN; MYOD AB Motor activity blocks the extrasynaptic expression of many genes in skeletal muscle, including those encoding ion channels, receptors, and adhesion molecules. Denervation reinduces transcription throughout the multinucleated myofiber, restoring the developmental pattern of expression, especially of the genes coding for the acetylcholine receptor. A screen for trans-acting factors binding to the enhancer region of the cu-subunit gene of the acetylcholine receptor identified CTF4, a ubiquitously expressed and alternatively spliced chicken homologue of the human E protein transcription factor HTF4/HEB, Expression of the CTF4 locus closely parallels that of myogenin and acetylcholine receptor during development and maturation of skeletal muscle, but transcription is not similarly regulated by neuronal cues. Alternative splicing within the region encoding the transactivation domain generates two CTF4 isoforms with different tissue distributions, but similar binding affinities for the acetylcholine receptor cu-subunit enhancer and similar transcriptional potential when complexed to myogenin, Direct injection of a myogenin, but not a MyoD, antisense expression vector into denervated skeletal muscle caused a significant decrease in the transcriptional activation of a depolarization-sensitive reporter gene. Similarly, injection of a CTF4, but less so of an E12, antisense expression vector impaired the denervation response, further implicating the involvement of a myogenin/CTF4 heterodimer in the expression of AChR genes in vivo. C1 SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Samsung Biomed Res Inst, Seoul 135230, South Korea. Yang Ming Med Univ, Inst Neurosci, Taipei 112, Taiwan. RP Schmidt, J (reprint author), SUNY Stony Brook, Dept Biochem & Cellular Biol, Stony Brook, NY 11794 USA. FU NINDS NIH HHS [NS20233] NR 48 TC 9 Z9 9 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 29 PY 1998 VL 273 IS 22 BP 14046 EP 14052 DI 10.1074/jbc.273.22.14046 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZQ947 UT WOS:000073919100095 PM 9593756 ER PT J AU Altare, F Durandy, A Lammas, D Emile, JF Lamhamedi, S Le Deist, F Drysdale, P Jouanguy, E Doffinger, R Bernaudin, F Jeppsson, O Gollob, JA Meinl, E Segal, AW Fischer, A Kumararatne, D Casanova, JL AF Altare, F Durandy, A Lammas, D Emile, JF Lamhamedi, S Le Deist, F Drysdale, P Jouanguy, E Doffinger, R Bernaudin, F Jeppsson, O Gollob, JA Meinl, E Segal, AW Fischer, A Kumararatne, D Casanova, JL TI Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency SO SCIENCE LA English DT Article ID IFN-GAMMA PRODUCTION; HUMAN T-CELLS; INFECTION; CYTOKINE; RESISTANCE; COMPLEX; PROTEIN; MICE AB In humans, interferon gamma (IFN-gamma) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas. Interleukin-12 (IL-12) receptor deficiency was found in otherwise healthy individuals with mycobacterial infections. Mature granulomas were seen, surrounded by T cells and centered with epithelioid and multinucleated giant cells, yet reduced IFN-gamma concentrations were found to be secreted by activated natural killer and T cells. Thus, IL-12-dependent IFN-gamma secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12-independent IFN-gamma secretion. C1 Hop Necker Enfants Malad, Unite Immunol & Hematol Pediat, F-75015 Paris, France. Hop Necker Enfants Malad, INSERM, U429, F-75015 Paris, France. UCL, Dept Med, London WC1 E6JJ, England. Univ Erlangen Nurnberg, D-91054 Erlangen, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Hosp, Dept Pediat, S-14501 Norsborg, Sweden. Ctr Hosp Intercommunal, Serv Pediat, F-94010 Creteil, France. Hop Paul Brousse, Serv Anatomopathol, F-94804 Villejuif, France. Univ Birmingham, Sch Med, Dept Immunol, Birmingham B15 2TT, W Midlands, England. RP Casanova, JL (reprint author), Hop Necker Enfants Malad, INSERM, U429, F-75015 Paris, France. EM casanova@ceylan.necker.fr OI Segal, Anthony/0000-0001-7602-9043 NR 39 TC 570 Z9 580 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 MAY 29 PY 1998 VL 280 IS 5368 BP 1432 EP 1435 DI 10.1126/science.280.5368.1432 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZQ591 UT WOS:000073883400055 PM 9603732 ER PT J AU Kogan, MD Martin, JA Alexander, GR Kotelchuck, M Ventura, SJ Frigoletto, FD AF Kogan, MD Martin, JA Alexander, GR Kotelchuck, M Ventura, SJ Frigoletto, FD TI The changing pattern of prenatal care utilization in the United States, 1981-1995, using different prenatal care indices SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LOW-BIRTH-WEIGHT; GESTATIONAL-AGE; PREGNANCY; MEDICAID; HEALTH; ADEQUACY; INDEXES; ULTRASOUND; LITIGATION; EXPANSION AB Context.-Two measures traditionally used to examine adequacy of prenatal care indicate that prenatal care utilization remained unchanged through the 1980s and only began to rise slightly in the 1990s. In recent years, new measures have been developed that include a category for women who receive more than the recommended amount of care (intensive utilization). Objective.-To compare the older and newer indices in the monitoring of prenatal care trends in the United States from 1981 to 1995, for the overall population and for selected subpopulations. Second, to examine factors associated with receiving intensive utilization. Design.-Cross-sectional and trend analysis of national birth records. Setting.-The United States. Subjects.-All live births between 1981 and 1995 (N=54 million). Main Outcome Measures.-Trends in prenatal care utilization, according to 4 indices (the older indices: the Institute of Medicine Index and the trimester that care began, and the newer indices: the R-GINDEX and the Adequacy of Prenatal Care Utilization Index). Multiple logistic regression was used to assess the risk of intensive prenatal care use in 1981 and 1995. Results.-The newer indices showed a steadily increasing trend toward more prenatal care use throughout the study period (R-GINDEX, intensive or adequate use, 32.7% in 1981 to 47.1% in 1995; the Adequacy of Prenatal Care Utilization Index, intensive use, 18.4% in 1981 to 28.8% in 1995), especially for intensive utilization. Women having a multiple birth were much more likely to have had intensive utilization in 1995 compared with 1981 (R-GINDEX, 22.8% vs 8.5%). Teenagers were more likely to begin care later than adults, but similar proportions of teens and adults had intensive utilization. Intensive use among low-risk women also increased steadily each year. Factors associated with a greater likelihood of receiving intensive use in 1981 and 1995 were having a multiple birth, primiparity, being married, and maternal age of 35 years or older. Conclusions.-The proportion of women who began care early and received at least the recommended number of visits increased between 1981 and 1995. This change was undetected by more traditional prenatal care indices. These increases have cost and practice implications and suggest a paradox since previous studies have shown that rates of preterm delivery and low birth weight did not improve during this time. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Univ Alabama, Dept Maternal & Child Hlth, Birmingham, AL USA. Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Obstet, Boston, MA USA. RP Kogan, MD (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 6525 Belcrest Rd,Room 820, Hyattsville, MD 20782 USA. NR 56 TC 141 Z9 144 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 27 PY 1998 VL 279 IS 20 BP 1623 EP 1628 DI 10.1001/jama.279.20.1623 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZP489 UT WOS:000073758600031 PM 9613911 ER PT J AU Mahmarian, JJ Moye, LA Chinoy, DA Sequeira, RF Habib, GB Henry, WJ Jain, A Chaitman, BR Weng, CSW Morales-Ballejo, H Pratt, CM AF Mahmarian, JJ Moye, LA Chinoy, DA Sequeira, RF Habib, GB Henry, WJ Jain, A Chaitman, BR Weng, CSW Morales-Ballejo, H Pratt, CM TI Transdermal nitroglycerin patch therapy improves left ventricular function and prevents remodeling after acute myocardial infarction - Results of a multicenter prospective randomized, double-blind, placebo-controlled trial SO CIRCULATION LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-Heart-Association CY NOV 09-18, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Heart Assoc, Natl Inst Alcohol Abuse & Alcoholism DE remodeling; myocardial infarction; nitroglycerin ID INTRAVENOUS NITROGLYCERIN; RADIONUCLIDE ANGIOGRAPHY; SIZE; CAPTOPRIL; DYSFUNCTION; EXPANSION; DILATION; ENLARGEMENT; TOPOGRAPHY; SURVIVAL AB Background-Nitrates are widely used in the treatment of angina in patients with acute myocardial infarction (AMI). Short-term administration prevents left ventricular (LV) dilation and infarct expansion. However, little information is available regarding their long-term effects on LV remodeling in patients surviving Q-wave AMI. Methods and Results-This was a randomized, double-blind, placebo-controlled trial designed to investigate the long-term (6-month) efficacy of intermittent transdermal nitroglycerin (NTG) patches on LV remodeling in 291 survivors of AMI. Patients meeting entry criteria had baseline gated radionuclide angiography (RNA) followed by randomization to placebo or active NTG patches delivering 0.4-, 0.8-, or 1.6-mg/h, RNA was repeated at 6 months and 6.5 days after withdrawal of double-blind medication. The primary study end point was the change in end-systolic volume index (ESVI), Both ESVI and end-diastolic volume index (EDVI) were significantly reduced with 0.4-mg/h NTG patches (-11.4 and -11.6 mL/m(2), respectively, P<.03). This beneficial effect was observed primarily in patients with a baseline LV ejection fraction less than or equal to 40% (Delta ESVI, -31 mL/m(2); Delta EDVI, -33 mL/m(2); both P<.05) and only at the 0.4-mg/h dose. After NTG patch withdrawal, ESVI significantly increased but did not reach pretreatment values. Conclusions-Transdermal NTG patches prevent LV dilation in patients surviving AMI, The beneficial effects are limited to patients with depressed LV function and only at the lowest (0.4-mg/h) dose. Continued administration is necessary to maintain efficacy. Whether these remodeling effects confer a clinical or survival advantage will need to be addressed in an adequately powered cardiac event trial. C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Ctr Controlled Clin Trials, Sch Publ Hlth, Houston, TX USA. Cardiovasc Clin, Jacksonville, FL USA. Univ Miami, Jackson Mem Hosp, Coral Gables, FL 33124 USA. Baylor Coll Med, Vet Adm Med Ctr, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. St Louis Univ, Sch Med, St Louis, MO 63103 USA. Schering Plough Corp, Kenilworth, NJ 07033 USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Mahmarian, JJ (reprint author), 6550 Fannin St,SM-1246, Houston, TX 77030 USA. EM johnj@bcm.tmc.edu NR 31 TC 33 Z9 34 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 26 PY 1998 VL 97 IS 20 BP 2017 EP 2024 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZP475 UT WOS:000073757200005 PM 9610531 ER PT J AU Matthews, AN Friend, DS Zimmerrmann, N Sarafi, MN Luster, AD Pearlman, E Wert, SE Rothenberg, ME AF Matthews, AN Friend, DS Zimmerrmann, N Sarafi, MN Luster, AD Pearlman, E Wert, SE Rothenberg, ME TI Eotaxin is required for the baseline level of tissue eosinophils SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHEMOATTRACTANT CYTOKINE; ALLERGIC INFLAMMATION; TRANSGENIC MICE; MESSENGER-RNA; BONE-MARROW; EXPRESSION; LUNG; RECRUITMENT; RECEPTOR; CELLS AB Eotaxin is an eosinophil-selective chemokine that is constitutively expressed in a variety of organs such as the intestine. Previous studies have demonstrated that the recruitment of eosinophils during inflammation is partially dependent on eotaxin, but the function of constitutive eotaxin during homeostasis has not been examined. To elucidate the biological role of this molecule, we now examine tissue levels of eosinophils in healthy states in wild-type and eotaxin-deficient mice. The lamina propria of the jejunum of wild-type mice is demonstrated to express eotaxin mRNA, but not mRNA for the related monocyte chemoattractant proteins. Wild-type mice contained readily detectable eosinophils in the lamina propria of the jejunum. In contrast, mice genetically deficient in eotaxin had a large selective reduction in the number of eosinophils residing in the jejunum. The reduction of tissue eosinophils was not limited to the jejunum,:because a loss of thymic eosinophils was also observed in eotaxin-deficient mice. These studies demonstrate that eotaxin is a fundamental regulator of the physiological trafficking of eosinophils during healthy states. Because a variety of chemokines are constitutively expressed, their involvement in the baseline trafficking of leukocytes into nonhematopoietic tissue should now be considered. C1 Childrens Hosp, Med Ctr, Dept Pediat, Div Pulm Med Allergy & Clin Immunol, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Dept Pediat, Div Neonatol & Pulm Biol, Cincinnati, OH 45229 USA. Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Infect Dis Unit, Boston, MA 02114 USA. Case Western Reserve Univ, Sch Med, Div Geog Med, Cleveland, OH 44106 USA. RP Rothenberg, ME (reprint author), Childrens Hosp, Med Ctr, Dept Pediat, Div Pulm Med Allergy & Clin Immunol, Cincinnati, OH 45229 USA. NR 37 TC 180 Z9 182 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 26 PY 1998 VL 95 IS 11 BP 6273 EP 6278 DI 10.1073/pnas.95.11.6273 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZQ352 UT WOS:000073852600076 PM 9600955 ER PT J AU Gong, JL Chen, DS Kashiwaba, M Li, YQ Chen, L Takeuchi, H Qu, H Rowse, GJ Gendler, SJ Kufe, D AF Gong, JL Chen, DS Kashiwaba, M Li, YQ Chen, L Takeuchi, H Qu, H Rowse, GJ Gendler, SJ Kufe, D TI Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELLS; ANTITUMOR IMMUNITY; HUMAN-MILK; PROTEIN; DF3; LYMPHOCYTES; REACTIVITY; INDUCTION; PEPTIDE AB Immunological unresponsiveness established by the elimination or anergy of self-reactive lymphocyte clones is of importance to immunization against tumor-associated antigens, In this study, we have investigated induction of immunity against the human MUC1 carcinoma-associated antigen in MUC1 transgenic mice unresponsive to MUC1 antigen. Immunization of adult MUC1 transgenic mice with irradiated MUC1-positive tumor cells was unsuccessful in reversing unresponsiveness to MUC1, By contrast, fusions of dendritic cells with MUC1-positive tumor cells induced cellular and humoral immunity against MUC1. Immunization with the dendritic cell fusions that express MUC1 resulted in the rejection of established metastases and no apparent autoimmunity against normal tissues. These findings demonstrate that unresponsiveness to the MUC1 tumor-associated antigen is reversible by immunization with heterokaryons of dendritic cells and MUC1-positive carcinoma cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Scottsdale, AZ 85259 USA. RP Gong, JL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 30 TC 196 Z9 198 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 MAY 26 PY 1998 VL 95 IS 11 BP 6279 EP 6283 DI 10.1073/pnas.95.11.6279 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZQ352 UT WOS:000073852600077 PM 9600956 ER PT J AU Zhang, CG Xu, YH Gu, JJ Schlossman, SF AF Zhang, CG Xu, YH Gu, JJ Schlossman, SF TI A cell surface receptor defined by a mAb mediates a unique type of cell death similar to oncosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DOMAIN-CONTAINING RECEPTOR; TUMOR-NECROSIS-FACTOR; MONOCLONAL-ANTIBODY; APOPTOSIS; FAS; IDENTIFICATION; DISEASE; MEMBER; FAMILY; CD95 AB Cell death is mediated by distinct pathways including apoptosis and oncosis in response to various death signals. To characterize molecules involved in cell death, a panel of mAbs was raised by immunizing mice with apoptotic cells. One of these antibodies, designated anti-Porimin (for pro-oncosis receptor inducing membrane injury), was found to directly induce a unique type of cell death in Jurkat cells. Anti-Porimin defines a 110-kDa cell surface receptor on Jurkat cells. Functionally, anti-Porimin alone rapidly mediates pore formation on the plasma membrane and induces cell death without participation of complement. Both the cellular expression and functional characteristics of the Porimin antigen indicate that it is distinct from the CD95 (Fas/Apo-1) and other cell receptors known to induce apoptosis. Anti-Porimin-mediated cell death was preceded by cell aggregation, formation of plasma membrane pores, and the appearance of membrane blebs. More important, these cells show neither DNA fragmentation nor apoptotic bodies, but display lethal damage of the cell membrane. Cell death by anti-Porimin is distinct from complement-dependent cytolysis or complement-independent apoptosis but is similar to that described for oncosis, a form of cell death accompanied by the membrane damage followed by karyolysis. The induction of cell death by anti-Porimin may represent a unique cell surface receptor-mediated pathway of cell death in the human lymphoid system. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Zhang, CG (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 12069] NR 34 TC 39 Z9 48 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 26 PY 1998 VL 95 IS 11 BP 6290 EP 6295 DI 10.1073/pnas.95.11.6290 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZQ352 UT WOS:000073852600079 PM 9600958 ER PT J AU Karet, FE Gainza, FJ Gyory, AZ Unwin, RJ Wrong, O Tanner, MJA Nayir, A Alpay, H Santos, F Hulton, SA Bakkaloglu, A Ozen, S Cunningham, MJ di Pietro, A Walker, WG Lifton, RP AF Karet, FE Gainza, FJ Gyory, AZ Unwin, RJ Wrong, O Tanner, MJA Nayir, A Alpay, H Santos, F Hulton, SA Bakkaloglu, A Ozen, S Cunningham, MJ di Pietro, A Walker, WG Lifton, RP TI Mutations in the chloride-bicarbonate exchanger gene AE1 cause autosomal dominant but not autosomal recessive distal renal tubular acidosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANION-TRANSPORT PROTEIN; HEREDITARY SPHEROCYTOSIS; LINKAGE ANALYSIS; COLLECTING DUCT; DNA; CONFORMATION; SEQUENCE; CHILDREN; TRAITS; MAP AB Primary distal renal tubular acidosis (dRTA) is characterized by reduced ability to acidify urine, variable hyperchloremic hypokalemic metabolic acidosis, nephrocalcinosis, and nephrolithiasis. Kindreds showing either autosomal dominant or recessive transmission are described. Mutations in the chloride-bicarbonate exchanger AE1 have recently been reported in four autosomal dominant dRTA kindreds, three of these altering codon Arg589. We have screened 26 kindreds with primary dRTA for mutations in AE1. Inheritance was autosomal recessive in seventeen kindreds, autosomal dominant in one, and uncertain due to unknown parental phenotype or sporadic disease in eight kindreds. No mutations in AE1 were detected in any of the autosomal recessive kindreds, and analysis of linkage showed no evidence of linkage of recessive dRTA to AE1. In contrast, heterozygous mutations in AE1 were identified in the one known dominant dRTA kindred, in one sporadic case, and one kindred with two affected brothers. In the dominant kindred, the mutation Arg-589/Ser cosegregated with dRTA in the extended pedigree. An Arg-589/His mutation in the sporadic case proved to be a de novo mutation. In the third kindred, affected brothers both have an intragenic 13-bp duplication resulting in deletion of the last 11 amino acids of AE1. These mutations were not detected in 80 alleles from unrelated normal individuals. These findings underscore the key role of Arg-589 and the C terminus in normal AE1 function, and indicate that while mutations in AE1 cause autosomal dominant dRTA, defects in this gene are not responsible for recessive disease. C1 Yale Univ, Sch Med, Dept Med, Boyer Ctr Mol Med,Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Genet, Boyer Ctr Mol Med,Howard Hughes Med Inst, New Haven, CT 06510 USA. Hosp Cruces, Baracaldo, Basque Country, Spain. Univ Sydney, Royal N Shore Hosp, St Leonards, NSW 2065, Australia. UCL, Inst Urol & Nephrol, London W1N 8AA, England. Univ Bristol, Dept Biochem, Bristol BS8 LTD, Avon, England. Univ Istanbul, Dept Pediat Nephrol, Istanbul, Turkey. Univ Oviedo, Div Pediat Nephrol, Oviedo, Spain. Childrens Hosp, Dept Nephrol, Birmingham B16 8ET, W Midlands, England. Hacettepe Univ, Childrens Hosp, Dept Pediat Nephrol, Ankara, Turkey. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Serv Osped Rilievo Nazl, Naples, Italy. Johns Hopkins Univ, Baltimore, MD 21205 USA. RP Lifton, RP (reprint author), Yale Univ, Sch Med, Dept Med, Boyer Ctr Mol Med,Howard Hughes Med Inst, Room 154,295 Congress Ave, New Haven, CT 06510 USA. EM richard_lifton@qm.yale.edu RI GAINZA, FRANCISCO/B-5385-2008 OI GAINZA, FRANCISCO/0000-0002-6695-6270 FU Wellcome Trust NR 34 TC 170 Z9 174 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 26 PY 1998 VL 95 IS 11 BP 6337 EP 6342 DI 10.1073/pnas.95.11.6337 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZQ352 UT WOS:000073852600087 PM 9600966 ER PT J AU Rosenzweig, M DeMaria, M Harper, DM Friedrich, S Jain, RK Johnson, RP AF Rosenzweig, M DeMaria, M Harper, DM Friedrich, S Jain, RK Johnson, RP TI Increased rates of CD4(+) and CD8(+) T lymphocyte turnover in simian immunodeficiency virus-infected macaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HIV-1 INFECTION; CELLS; TELOMERES; DEATH; AIDS AB Defining the rate at which T cells turn over has important implications for our understanding of T lymphocyte homeostasis and AIDS pathogenesis, yet little information on T cell turnover is available. We used the nucleoside analogue bromodeoxyuridine (BrdUrd) in combination with five-color flow cytometric analysis to evaluate T lymphocyte turnover rates in normal and simian immunodeficiency virus (SIV)-infected rhesus macaques, T cells in normal animals turned over at relatively rapid rates, with memory cells turning over more quickly than naive cells, In SIV-infected animals, the labeling and elimination rates of both CD4(+) and CD8(+) BrdUrd-labeled cells were increased by 2-to 3-fold as compared with normal controls. In normal and SIV-infected animals, the rates of CD4(+) T cell BrdUrd-labeling and decay were closely correlated with those of CD8(+) T cells, The elimination rate of BrdUrd-labeled cells was accelerated in both naive and memory T lymphocytes in SIV-infected animals. Our results provide direct evidence for increased rates of both CD4(+) and CD8(+) T cell turnover in AIDS virus infection and have important implications for our understanding of T cell homeostasis and the mechanisms responsible for CD4(+) T cell depletion in AIDS. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Charlestown, MA 02129 USA. RP Rosenzweig, M (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, POB 9102,1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCRR NIH HHS [K26 RR000168, RR-00168, P51 RR000168]; NIAID NIH HHS [AI-36550] NR 36 TC 83 Z9 85 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 26 PY 1998 VL 95 IS 11 BP 6388 EP 6393 DI 10.1073/pnas.95.11.6388 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZQ352 UT WOS:000073852600096 PM 9600975 ER PT J AU Cha, JHJ Kosinski, CM Kerner, JA Alsdorf, SA Mangiarini, L Davies, SW Penney, JB Bates, GP Young, AB AF Cha, JHJ Kosinski, CM Kerner, JA Alsdorf, SA Mangiarini, L Davies, SW Penney, JB Bates, GP Young, AB TI Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human Huntington disease gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID METABOTROPIC GLUTAMATE RECEPTORS; BINDING-SITES; QUANTITATIVE AUTORADIOGRAPHY; QUINOLINIC ACID; NERVOUS-SYSTEM; BASAL GANGLIA; MESSENGER-RNA; RAT; STRIATUM; 6-HYDROXYDOPAMINE AB Loss of neurotransmitter receptors, especially glutamate and dopamine receptors, is one of the pathologic hallmarks of brains of patients with Huntington disease (HD). Transgenic mice that express exon 1 of an abnormal human HD gene (line R6/2) develop neurologic symptoms at 9-11 weeks of age through an unknown mechanism. Analysis of glutamate receptors (GluRs) in symptomatic 12-week-old R6/2 mice revealed decreases compared with age-matched littermate controls in the type 1 metabotropic GluR (mGluR1), mGluR2, mGluR3, but not the mGluR5 subtype of G protein-linked mGluR, as determined by [(3)H]glutamate receptor binding, protein immunoblotting, and in situ hybridization. Ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors were also decreased, while N-methyl-D-aspartic acid receptors were not different compared with controls. Other neurotransmitter receptors known to be affected in HD were also decreased in R6/2 mice, including dopamine and muscarinic cholinergic, but not gamma-aminobutyric acid receptors. D(1)-like and D(2)-like dopamine receptor binding was drastically reduced to one-third of control in the brains of 8- and 12-week-old R6/2 mice. In situ hybridization indicated that mGluR and D(1) dopamine receptor mRNA were altered as early as 4 weeks of age, long prior to the onset of clinical symptoms. Thus, altered expression of neurotransmitter receptors precedes clinical symptoms in R6/2 mice and may contribute to subsequent pathology. C1 Massachusetts Gen Hosp, Serv Neurol, Dept Neurol, Boston, MA 02114 USA. Guys Hosp, UMDS, Div Med & Mol Genet, London SE1 9RT, England. UCL, Dept Anat & Dev Biol, London WC1E 6BY, England. RP Young, AB (reprint author), Massachusetts Gen Hosp, Serv Neurol, Dept Neurol, VBK 915, Boston, MA 02114 USA. EM young@helix.mgh.harvard.edu RI Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 FU NIA NIH HHS [AG 11337, R01 AG013617, R37 AG013617]; NINDS NIH HHS [NS01916, NS31579] NR 45 TC 369 Z9 373 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 26 PY 1998 VL 95 IS 11 BP 6480 EP 6485 DI 10.1073/pnas.95.11.6480 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZQ352 UT WOS:000073852600113 PM 9600992 ER PT J AU Han, XQ Kubota, I Feron, O Opel, DJ Arstall, MA Zhao, YY Huang, P Fishman, MC Michel, T Kelly, RA AF Han, XQ Kubota, I Feron, O Opel, DJ Arstall, MA Zhao, YY Huang, P Fishman, MC Michel, T Kelly, RA TI Muscarinic cholinergic regulation of cardiac myocyte ICa-L is absent in mice with targeted disruption of endothelial nitric oxide synthase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PIG VENTRICULAR MYOCYTES; MAMMALIAN HEART-RATE; CA2+ CURRENT; INOTROPIC RESPONSE; SIGNALING SYSTEM; CALCIUM CHANNELS; MUSCLE-CELLS; ION CHANNELS; ACETYLCHOLINE; MODULATION AB Cardiac myocytes have been shown to express constitutively endothelial nitric oxide synthase (eNOS) (nitric oxide synthase 3), the activation of which has been implicated in the regulation of myocyte L-type voltage-sensitive calcium channel current (ICa-L) and myocyte contractile responsiveness to parasympathetic nervous system signaling, although this implication remains controversial. Therefore, we examined the effect of the muscarinic cholinergic agonist carbachol (CCh) on ICa-L and contractile amplitude in isoproterenol (ISO)-prestimulated ventricular myocytes isolated from adult mice, designated eNOS(null) mice, with targeted disruption of the eNOS gene. Although both eNOS(null) and wild type (WT) ventricular myocytes exhibited similar increases in ICa-L in response to ISO, there was no measurable suppression of ICa-L by CCh in cells from eNOS(null) mice, in contrast to cells from WT mice. These results were reflected in the absence of an effect of CCh on the positive inotropic effect of ISO in eNOS(null) myocytes. Also, unlike myocytes from WT animals, eNOS(null) myocytes failed to exhibit an increase in cGMP content in response to CCh. Nevertheless, the pharmacologic nitric oxide donors 3-morpholino-sydnonimine and S-nitroso acetyl-cystein increased cGMP generation and suppressed ISO-augmented ICa-L in eNOS(null) cells, suggesting that the signal transduction pathway(s) downstream of eNOS remained intact. Of importance, activation of the acetylcholine-activated K+ channel by CCh was unaffected in atrial and ventricular eNOS(null) myocytes. These results confirm the obligatory role of eNOS in coupling muscarinic receptor activation to cGMP-dependent control of ICa-L in cardiac myocytes. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Inst, Boston, MA 02115 USA. RP Han, XQ (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM xhan@bustoff.bwh.harvard.edu; rakelly@bics.bwh.harvard.edu FU NHLBI NIH HHS [HL52320, P50 HL052320] NR 47 TC 122 Z9 126 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 MAY 26 PY 1998 VL 95 IS 11 BP 6510 EP 6515 DI 10.1073/pnas.95.11.6510 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZQ352 UT WOS:000073852600118 PM 9600997 ER PT J AU Giugliano, RP Camargo, CA Lloyd-Jones, DM Zagrodsky, JD Alexis, JD Eagle, KA Fuster, V O'Donnell, CJ AF Giugliano, RP Camargo, CA Lloyd-Jones, DM Zagrodsky, JD Alexis, JD Eagle, KA Fuster, V O'Donnell, CJ TI Elderly patients receive less aggressive medical and invasive management of unstable angina - Potential impact of practice guidelines SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; RANDOMIZED CLINICAL-TRIALS; DOUBLE-BLIND; UNITED-STATES; THROMBOLYTIC THERAPY; HEART-DISEASE; CARE UNIT; NEW-HAVEN; ASPIRIN AB Background: The Agency for Health Care Policy and Research (AHCPR) released a practice guideline on the diagnosis and management of unstable angina in 1994. Objective: To examine practice variation across the age spectrum in the management of patients hospitalized with unstable angina 2 years before release of the AHCPR guideline. Design: Retrospective cohort. Setting: Urban academic hospital. Patients: All nonreferral patients diagnosed as having unstable angina who were hospitalized directly from the emergency department to the intensive care or telemetry unit between October 1, 1991, and September 30, 1992. Measurements: Percentage of eligible patients receiving medical treatment concordant with 8 important AHCPR guideline recommendations. Results: Half of the 280 patients were older than 66 years; women were older than men on average (70 vs 64 years; P<.001). After excluding those with contraindications to therapy, patients in the oldest quartile (age, 75.20-93.37 years) were less likely than younger patients to receive aspirin (P<.009), P-blockers (P<.04), and referral for cardiac catheterization (P<.001). Overall guideline concordance weighted for the number of eligible patients declined with increasing age (87.4%, 87.4%, 84.0%, and 74.9% for age quartiles 1 to 4, respectively; chi(2), P<.001). Increasing age, the presence of congestive heart failure at presentation, a history of congestive heart failure, previous myocardial infarction, increasing comorbidity, and elevated creatinine concentration were associated with care that was less concordant with AHCPR guideline recommendations; only age and congestive heart failure at presentation remained significant in the multivariate analysis (odds ratios, 1.28 per decade [95% confidence interval, 1.02-1.61] and 3.16 [95% confidence interval, 1.57-6.36], respectively). Conclusions: Older patients were less likely to receive standard therapies for unstable angina before release of the 1994 AHCPR guideline. Patients presenting with congestive heart failure also received care that was more discordant with guideline recommendations. The AHCPR guideline allows identification of patients who receive nonstandard care and, if applied to those patients with the greatest likelihood to benefit, could lead to improved health care delivery. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA. Univ Michigan, Med Ctr, Div Cardiol, Ann Arbor, MI 48109 USA. Mt Sinai Med Ctr, Cardiovasc Res Inst, New York, NY 10029 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Giugliano, RP (reprint author), Brigham & Womens Hosp, TIMI Study Chairmans Off, 75 Francis St, Boston, MA 02115 USA. EM rgiugliano@rics.bwh.harvard.edu RI Lloyd-Jones, Donald/C-5899-2009; Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 FU NHLBI NIH HHS [HL-03533, HL-07575] NR 69 TC 79 Z9 79 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 25 PY 1998 VL 158 IS 10 BP 1113 EP 1120 DI 10.1001/archinte.158.10.1113 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA ZP307 UT WOS:000073739200008 PM 9605783 ER PT J AU Passani, L Elkabes, S Coyle, JT AF Passani, L Elkabes, S Coyle, JT TI Evidence for the presence of N-acetylaspartylglutamate in cultured oligodendrocytes and LPS activated microglia SO BRAIN RESEARCH LA English DT Article DE N-acetylaspartylglutamate; oligodendrocyte; microglia; Alzheimer's disease; Huntington's disease; excitatory amino acid; peptide ID ACETYL-ASPARTYL-GLUTAMATE; MURINE BRAIN; RELEASE; BETA; SURVIVAL; NEURONS; CELLS AB The levels of N-acetylaspartylglutamate (NAAG) were determined by HPLC in untreated or lipopolysaccharide (LPS) activated pure astrocyte, oligodendrocyte, and microglial cultures derived from developing rat brain. Oligodendrocyte cultures expressed 1.52 +/- 0.12 nmol/mu g protein of NAAG, whereas astrocyte cultures (0.04 +/- 0.08 nmol/mu g protein) and untreated microglial cultures (0.05 +/- 0.09 nmol/mu g protein) contained only trace amounts of the dipeptide. After stimulation of microglial cultures for 24 h with LPS, NAAG levels increased significantly to 0.37 +/- 0.12 SD nmol/mu g protein. NAAG levels in astrocyte and oligodendrocyte cultures remained unchanged after LPS treatment. The findings indicate that NAAG is localized to specific glial cell types. Further our results suggest that NAAG biosynthesis is induced in microglia, activated by specific stimuli. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Charlestown, MA 02129 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurosci & Cell Biol, Piscataway, NJ 08854 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. RP Coyle, JT (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. EM jcoyle@warren.med.harvard.edu FU NIMH NIH HHS [MH-572901] NR 22 TC 25 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 25 PY 1998 VL 794 IS 1 BP 143 EP 145 DI 10.1016/S0006-8993(98)00308-4 PG 3 WC Neurosciences SC Neurosciences & Neurology GA ZX048 UT WOS:000074475000016 PM 9630582 ER PT J AU Kee, KS Kern, RS Marshall, BD Green, MF AF Kee, KS Kern, RS Marshall, BD Green, MF TI Risperidone versus haloperidol for perception of emotion in treatment-resistant schizophrenia: preliminary findings SO SCHIZOPHRENIA RESEARCH LA English DT Article DE risperidone; haloperidol; emotion perception; schizophrenia ID GENERALIZED POOR PERFORMANCE; SOCIAL SKILL; RECOGNITION; DISORDERS AB Currently, little is known about the pharmacological effects of the new generation of antipsychotic medications on perception of emotion in schizophrenia. The present study was designed to compare the effects of risperidone versus haloperidol on the ability to perceive emotion in 20 treatment-resistant schizophrenia patients, using a double-blind design. Measures of emotion perception included a facial emotion identification test (still photographs presented on videotape), a voice emotion identification test (audiotape), and an affect perception lest (brief interpersonal vignettes presented on videotape). These measures were administered during the final week of baseline and after 8 weeks of double-blind medication. Risperidone treatment produced a greater effect cn patients' ability to perceive emotion compared with haloperidol treatment. Additionally, all patients who received risperidone demonstrated improvement in performance between baseline and retest, compared with four of the nine patients who received haloperidol. When changes in positive symptoms were statistically controlled, the results remained significant. These findings suggest that risperidone may facilitate patients' ability to accurately perceive emotion, an effect which may be mediated either directly by risperidone's pharmacological action or perhaps indirectly by its influence on basic neurocognition. (C) 1998 Elsevier Science B.V. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Camarillo State Hosp & Dev Ctr, Camarillo, CA USA. RP Kee, KS (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,116AR,Bldg 208, Los Angeles, CA 90073 USA. EM kee@ucla.edu FU NIMH NIH HHS [MH-14584] NR 24 TC 76 Z9 77 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAY 25 PY 1998 VL 31 IS 2-3 BP 159 EP 165 DI 10.1016/S0920-9964(98)00026-7 PG 7 WC Psychiatry SC Psychiatry GA ZX838 UT WOS:000074560500010 PM 9689720 ER PT J AU Weitkamp, LR Tackels, DC Hunter, AGW Holmes, LB Schwartz, CE AF Weitkamp, LR Tackels, DC Hunter, AGW Holmes, LB Schwartz, CE TI Heterozygote advantage of the MTHFR gene in patients with neural-tube defect and their relatives SO LANCET LA English DT Article ID REDUCTASE C1 Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Div Genet, Rochester, NY 14642 USA. Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA. Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. RP Weitkamp, LR (reprint author), Univ Rochester, Sch Med & Dent, Dept Psychiat, Rochester, NY 14642 USA. FU NICHD NIH HHS [HD-24560]; PHS HHS [U85/CCU408774] NR 4 TC 25 Z9 25 U1 1 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY 23 PY 1998 VL 351 IS 9115 BP 1554 EP 1555 DI 10.1016/S0140-6736(05)61119-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZQ497 UT WOS:000073868000014 PM 10326541 ER PT J AU Atwood, CS Moir, RD Huang, XD Scarpa, RC Bacarra, NME Romano, DM Hartshorn, MK Tanzi, RE Bush, AI AF Atwood, CS Moir, RD Huang, XD Scarpa, RC Bacarra, NME Romano, DM Hartshorn, MK Tanzi, RE Bush, AI TI Dramatic aggregation of Alzheimer A beta by Cu(II) is induced by conditions representing physiological acidosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID AMYLOID PROTEIN DEPOSITION; C-REACTIVE PROTEIN; SEVERE HEAD-INJURY; CEREBROSPINAL-FLUID; APOLIPOPROTEIN-E; RAT-BRAIN; DENSITY-LIPOPROTEIN; HUMAN TRANSFERRIN; BINDING SITES; HIGH-AFFINITY AB The cortical deposition of A beta is an event that occurs in Alzheimer's disease, Down's syndrome, head injury, and normal aging. Previously, in appraising the effects of different neurochemical factors that impact upon the solubility of A beta, we observed that Zn2+ was the predominant bioessential metal to induce the aggregation of soluble A beta at pH 7.4 in vitro and that this reaction is totally reversible with chelation. We now report that unlike other biometals tested at maximal biological concentrations, marked Cu2+-induced aggregation of A beta(1-40) emerged as the solution pH was lowered from 7.4 to 6.8 and that the reaction was completely reversible with either chelation or alkalinization. This interaction was comparable to the pH-dependent effect of Cu2+ On insulin aggregation but was not seen for aprotinin or albumin. A beta(1-40) bound three to four Cu2+ ions when precipitated at pH 7.0. Rapid, pH-sensitive aggregation occurred at low nanomolar concentrations of both A beta(1-40) and A beta(1-42) with submicromolar concentrations of Cu2+. Unlike A beta(1-40) AP(1-42) was precipitated by submicromolar Cu2+ concentrations at pH 7.4, Rat A beta(1-40) and histidine-modified human A beta(1-40) were not aggregated by Zn2+, Cu2+, Or Fe3+, indicating that histidine residues are essential for metal-mediated A beta assembly. These results indicate that H+-induced conformational changes unmask a metal-binding site on A beta that mediates reversible assembly of the peptide. Since a mildly acidic environment together with increased Zn2+ and Cu2+ are common features of inflammation, we propose that AP aggregation by these factors may be a response to local injury. Cu2+, Zn2+ and Fe3+ association with A beta explains the recently reported enrichment of these metal ions in amyloid plaques in Alzheimer's disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Bush, AI (reprint author), Massachusetts Gen Hosp E, Ctr Neurosci, Genet & Aging Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. EM bush@helix.mgh.harvard.edu RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [1R29AG1268601] NR 106 TC 768 Z9 793 U1 4 U2 92 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 22 PY 1998 VL 273 IS 21 BP 12817 EP 12826 DI 10.1074/jbc.273.21.12817 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZP588 UT WOS:000073768500020 PM 9582309 ER PT J AU Endres, M Scott, G Namura, S Salzman, AL Huang, PL Moskowitz, MA Szabo, C AF Endres, M Scott, G Namura, S Salzman, AL Huang, PL Moskowitz, MA Szabo, C TI Role of peroxynitrite and neuronal nitric oxide synthase in the activation of poly(ADP-ribose) synthetase in a murine model of cerebral ischemia-reperfusion SO NEUROSCIENCE LETTERS LA English DT Article DE neuronal nitric oxide synthase; peroxynitrite; poly(ADP-ribose) synthetase; cerebral ischemia; reperfusion ID DNA STRAND BREAKAGE; NEUROTOXICITY AB Poly(ADP-ribose) synthetase (PARS) activation, a downstream event of nitric oxide (NO) neurotoxicity has been implicated in cerebral reperfusion injury. The aim of our study was to identify the trigger of PARS activation during stroke. Formation of poly(ADP-ribose) profoundly increased in the early phase of reperfusion. Poly(ADP-ribose) formation was attenuated in mice deficient for neuronal NO synthase (nNOS). We next tested in glioma cells whether NO, or peroxynitrite (a cytotoxic oxidant formed from NO and superoxide) is the actual trigger of PARS activation. Peroxynitrite, but not various NO donors, activated PARS and suppressed cellular viability in a PARS-dependent fashion. Thus, nNOS is responsible for PARS activation in stroke. PARS activation, however, is not a direct result of NO production, but it occurs via peroxynitrite formation. (C) 1998 Elsevier Science Ireland Ltd. C1 Childrens Hosp, Med Ctr, Div Crit Care, Cincinnati, OH 45229 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Szabo, C (reprint author), Childrens Hosp, Med Ctr, Div Crit Care, 3333 Burnet Ave, Cincinnati, OH 45229 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828] NR 21 TC 84 Z9 85 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 22 PY 1998 VL 248 IS 1 BP 41 EP 44 DI 10.1016/S0304-3940(98)00224-9 PG 4 WC Neurosciences SC Neurosciences & Neurology GA ZT774 UT WOS:000074124300011 PM 9665659 ER PT J AU Kawasaki, H Eckner, R Yao, TP Taira, K Chiu, R Livingston, DM Yokoyama, KK AF Kawasaki, H Eckner, R Yao, TP Taira, K Chiu, R Livingston, DM Yokoyama, KK TI Distinct roles of the co-activators p300 and CBP in retinoic-acid-induced F9-cell differentiation SO NATURE LA English DT Article ID 300 KDA PROTEIN; TRANSCRIPTIONAL ADAPTER; COACTIVATOR; CELLS; APOPTOSIS; ANTIGEN; TARGET; E1A AB The related proteins p300 and CBP (cAMP-response-element-binding protein (CREB)-binding protein)) are transcriptional co-activators that act with other factors to regulate gene expression(1-5) and play roles in many cell-differentiation add signal transduction pathways(6-10). Both proteins have intrinsic histone-acetyltransferase activity(11,12) and may act directly on chromatin, of which histone is a component, to facilitate transcription. They are also involved in growth control pathways, as shown by their interaction with the tumour-suppressor p53 (refs 13-15) and the viral oncogenes E1A (refs 1, 2, 16) and SV40 T antigen(5). Here we report functional differences of p300 and CBP in vivo. We examined their roles during retinoic-acid-induced differentiation, cell-cycle exit and programmed cell death (apoptosis) of embryonal carcinoma F9 cells(17,20), using hammerhead ribozymes capable of cleaving either p300 or CBP messenger RNAs. F9 cells expressing a p300-specific ribozyme became resistant to retinoic-acid-induced differentiation, whereas cells expressing a CBP-specific ribozyme were unaffected. Similarly, retinoic-acid-induced transcriptional upregulation of the cell-cycle inhibitor p21(Cip1) required normal levels of p300, but not CBP, whereas the reverse was true for p27(Kip1). In contrast, both ribozymes blocked retinoic-acid-induced apoptosis, indicating that both co-activators are required for this process. Thus, despite their similarities, p300 and CBP have distinct functions during retinoic-acid-induced differentiation of F9 cells. C1 Inst Phys & Chem Res, Tsukuba Life Sci Ctr, Tsukuba Sci City 3050074, Japan. Univ Tsukuba, Inst Appl Biochem, Tsukuba Sci City 3050006, Japan. Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Dept Surg Oncol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Yokoyama, KK (reprint author), Inst Phys & Chem Res, Tsukuba Life Sci Ctr, 3-1-1 Koyadai, Tsukuba Sci City 3050074, Japan. NR 28 TC 271 Z9 274 U1 1 U2 4 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 21 PY 1998 VL 393 IS 6682 BP 284 EP 289 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZP513 UT WOS:000073761000058 PM 9607768 ER PT J AU Bazzino, O Barrero, C Garre, L Sosa, A Aylward, P Slany, J Beaudry, P Bedard, J DeLarochelliere, R Nguyen, M Bogaty, P Boudreault Jr Diodati, JG Dupuis, J Fitchett, D Fung, A Gervais, P Gossard, D Grandmont, D Huynh, T Kouz, S Langer, A Laramee, P Lemay, M Maillette, S Maranda, C Nasmith, J Pesant, Y Phanuef, D Proulx, G Ruel, M Thompson, C Corbalan, R Botero, R Husted, S Heikkila, J Charbonnier, B Moguel, R Commerford, P Landless, P Weich, D Maritz, F Marx, J Fernandes, F Lidon, R Sanz, G Bosch X Moccetti, T Ali, N Anderson, HV Bajwa, T Borzak, S Boyek, T Brewer, D Cambier, P Chivukula, S Corder, C Ezekowitz, M Feldman, R Glickman, L Jang, IK Klein, M Korn, D Kraus, S Kwan, T Mann, JT Marshall, J Martin, J Monrad, ES Mueller, H Penny, W Schmedtje, J Strony, J Armstrong, P DeCani, J Hirsh, J Pepine, C Ryan, TJ Theroux, P Catella-Lawson, F Diodati, J Roy, L Willerson, JT Yusuf, S Zhao X Sax, FL Harris, KH Pelletier, G Davies, R Flather, M Gosselin, G Herrmann, H Kells, C Knudtson, M Thadani, U Snapinn, SM Ghannam, A Haggert, B Watson, A Lis, J Brancato, C Fong, D AF Bazzino, O Barrero, C Garre, L Sosa, A Aylward, P Slany, J Beaudry, P Bedard, J DeLarochelliere, R Nguyen, M Bogaty, P Boudreault, JR Diodati, JG Dupuis, J Fitchett, D Fung, A Gervais, P Gossard, D Grandmont, D Huynh, T Kouz, S Langer, A Laramee, P Lemay, M Maillette, S Maranda, C Nasmith, J Pesant, Y Phanuef, D Proulx, G Ruel, M Thompson, C Corbalan, R Botero, R Husted, S Heikkila, J Charbonnier, B Moguel, R Commerford, P Landless, P Weich, D Maritz, F Marx, J Fernandes, F Lidon, R Sanz, G Bosch, X Moccetti, T Ali, N Anderson, HV Bajwa, T Borzak, S Boyek, T Brewer, D Cambier, P Chivukula, S Corder, C Ezekowitz, M Feldman, R Glickman, L Jang, IK Klein, M Korn, D Kraus, S Kwan, T Mann, JT Marshall, J Martin, J Monrad, ES Mueller, H Penny, W Schmedtje, J Strony, J Armstrong, P DeCani, J Hirsh, J Pepine, C Ryan, TJ Theroux, P Catella-Lawson, F Diodati, J Roy, L Willerson, JT Yusuf, S Zhao, X Sax, FL Harris, KH Pelletier, G Davies, R Flather, M Gosselin, G Herrmann, H Kells, C Knudtson, M Thadani, U Snapinn, SM Ghannam, A Haggert, B Watson, A Lis, J Brancato, C Fong, D CA PRISM PLUS Investigators TI Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED TRIAL; HEPARIN; CLASSIFICATION; MECHANISMS; ANTAGONIST; DISEASE; ASPIRIN; MK-383 AB Background Antithrombotic therapy improves the prognosis of patients with acute coronary syndromes, yet the syndromes remain a therapeutic challenge. We evaluated tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor, in the treatment of unstable angina and non-Q-wave myocardial infarction. Methods A total of 1915 patients were randomly assigned in a double-blind manner to receive tirofiban, heparin, or tirofiban plus heparin. Patients received aspirin if its use was not contraindicated. The study drugs were infused for a mean (+/-SD) of 71.3+/-20 hours, during which time coronary angiography and angioplasty were performed when indicated after 48 hours. The composite primary end point consisted of death, myocardial infarction, or refractory ischemia within seven days after randomization. Results The study was stopped prematurely for the group receiving tirofiban alone because of excess mortality at seven days (4.6 percent, as compared with 1.1 percent for the patients treated with heparin alone). The frequency of the composite primary end point at seven days was lower among the patients who received tirofiban plus heparin than among those who received heparin alone (12.9 percent vs, 17.9 percent; risk ratio, 0.68; 95 percent confidence interval, 0.53 to 0.88; P=0.004). The rates of the composite end point in the tirofiban-plus-heparin group were also lower than those in the heparin-only group at 30 days (18.5 percent vs. 22.3 percent, P=0.03) and at 6 months (27.7 percent vs, 32.1 percent, P=0.02). At seven days, the frequency of death or myocardial infarction was 4.9 percent in the tirofiban-plus-heparin group, as compared with 8.3 percent in the heparin-only group (P=0.006). The comparable figures at 30 days were 8.7 percent and 11.9 percent (P=0.03), respectively, and those at 6 months were 12.3 percent and 15.3 percent (P=0.06). The benefit was consistent in the various subgroups of patients and in those treated medically as well as those treated with angioplasty. Major bleeding occurred in 3.0 percent of the patients receiving heparin alone and 4.0 percent of the patients receiving combination therapy (P=0.34). Conclusions When administered with heparin and aspirin, the platelet glycoprotein IIb/IIIa receptor inhibitor tirofiban was associated with a lower incidence of ischemic events in patients with acute coronary syndromes than in patients who received only heparin and aspirin. (C) 1998, Massachusetts Medical Society. C1 Italian Hosp, Buenos Aires, DF, Argentina. Clin Bazterrica, Buenos Aires, DF, Argentina. Hosp Naval, Buenos Aires, DF, Argentina. Sanatorio Bartoleme, Buenos Aires, DF, Argentina. Flinders Med Ctr, Flinders, SA, Australia. Krankenanstalt Rudolfstiftung Wien, Vienna, Austria. Cent Hosp Ste Marie, Trois Rivieres, PQ, Canada. Ctr Hosp Sherbrooke, Sherbrooke, PQ, Canada. Laval Hosp, Quebec City, PQ, Canada. Hop Enfants Jesus, Quebec City, PQ, Canada. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. McGill Univ, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. Vancouver Gen Hosp, Vancouver, BC, Canada. Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. Ctr Hosp Honore Mercier, St Hyacinthe, PQ, Canada. Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. Ctr Hosp Reg Lanaudiere, Joliette, PQ, Canada. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Montreal, Notre Dame Hosp, Montreal, PQ H3C 3J7, Canada. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Ctr Hosp Pierre Boucher, Longueuil, PQ, Canada. Queen Elizabeth Hosp, Montreal, PQ, Canada. Sacre Coeur Hosp, Montreal, PQ, Canada. Hotel Dieu St Jerome, St Jerome, PQ, Canada. Hotel Dieu Montreal, Montreal, PQ, Canada. Hotel Dieu Quebec, Quebec City, PQ, Canada. Hop St Luc, Montreal, PQ H2X 1P1, Canada. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Hosp Clin Univ Catolica, Santiago, Chile. Cardiovasc Clin, Medellin, Colombia. Ctr Med Fdn Valle Lili, Cali, Colombia. Skejby Hosp, Aarhus, Denmark. Helsinki Univ Hosp, Helsinki, Finland. Ctr Hosp Univ Trousseau, Tours, France. Hosp Reg Octubre, Mexico City, DF, Mexico. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Johannesburg Hosp, Parktown, South Africa. Tygerberg Hosp, Cape Town, South Africa. Univ Hosp, Bloemfontein, South Africa. Serv Cardiol, Valladolid, Spain. Hosp Gen Valle Hebron, Barcelona, Spain. Hosp Clin Barcelona, Barcelona, Spain. Osped Civico, Lugano, Switzerland. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Sch Med, Houston, TX USA. Sinai Samaritan Med Ctr, Milwaukee, WI USA. Henry Ford Hosp, Detroit, MI 48202 USA. Chester Cty Hosp, W Chester, PA USA. St Francis Hosp, Tulsa, OK USA. Madigan Army Med Ctr, Tacoma, WA 98431 USA. Lower Bucks Hosp, Bristol, PA USA. Oklahoma Fdn Cardiovasc Res, Oklahoma City, OK USA. W Haven Vet Affairs Med Ctr, New Haven, CT USA. Monroe Med Ctr, Ocala, FL USA. Mercer Med Ctr, Trenton, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Med Ctr, Boston, MA USA. Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. Albuquerque Med Ctr, Albuquerque, NM USA. SUNY Brooklyn, Brooklyn, NY USA. Wake Heart Associates, Raleigh, NC USA. Atlanta Vet Affairs Med Ctr, Atlanta, GA USA. Bryn Mawr Hosp, Bryn Mawr, PA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Montefiore Hosp, Bronx, NY USA. Univ Calif San Diego, Vet Affairs Med Ctr, San Diego, CA 92161 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Theroux, P (reprint author), Montreal Heart Inst, 5000 Belanger St E, Montreal, PQ H1T 1C8, Canada. RI Dupuis, Jocelyn/B-3898-2009; Bosch, Xavier/E-7890-2014; Dupuis, Jocelyn/C-6613-2013 OI Dupuis, Jocelyn/0000-0002-3193-1014 NR 28 TC 1157 Z9 1183 U1 1 U2 17 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 21 PY 1998 VL 338 IS 21 BP 1488 EP 1497 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA ZN943 UT WOS:000073699100002 ER PT J AU Sax, PE Trotman-Dickenson, B Klein, RS Mark, EJ AF Sax, PE Trotman-Dickenson, B Klein, RS Mark, EJ TI Pneumonia and the acute respiratory distress syndrome in a 24-year-old man - Psittacosis, causing the acute respiratory distress syndrome. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COMMUNITY-ACQUIRED PNEUMONIA; LEGIONNAIRES-DISEASE; REQUIRING HOSPITALIZATION; RADIOGRAPHIC FEATURES; TRACT INFECTIONS; Q-FEVER; ETIOLOGY; DIAGNOSIS; TULAREMIA; ADULTS C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sax, PE (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. NR 53 TC 1 Z9 1 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 21 PY 1998 VL 338 IS 21 BP 1527 EP 1535 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA ZN943 UT WOS:000073699100008 ER PT J AU Brunet, JS Ghadirian, P Rebbeck, TR Lerman, C Garber, JE Tonin, PN Abrahamson, J Foulkes, WD Daly, M Wagner-Costalas, J Godwin, A Olopade, OI Moslehi, R Liede, A Futreal, PA Weber, BL Lenoir, GM Lynch, HT Narod, SA AF Brunet, JS Ghadirian, P Rebbeck, TR Lerman, C Garber, JE Tonin, PN Abrahamson, J Foulkes, WD Daly, M Wagner-Costalas, J Godwin, A Olopade, OI Moslehi, R Liede, A Futreal, PA Weber, BL Lenoir, GM Lynch, HT Narod, SA TI Effect of smoking on breast cancer in carriers of mutant BRCA1 or BRCA2 genes SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GROWTH-FACTOR-I; CIGARETTE-SMOKING; RISK; WOMEN; ESTROGENS; HORMONE; WEIGHT; AGE; SEX AB Background: Smoking has carcinogenic effects, and possibly antiestrogenic effects as well, but it has not been found to be a risk factor for breast cancer in women in the general population. However, hereditary breast cancer is primarily a disease of premenopausal women, and interactions between genes and hormonal and environmental risk factors may be particularly important in this subgroup. Methods: We conducted a matched case-control study of breast cancer among women who have been identified to be carriers of a deleterious mutation in either the BRCA1 or the BRCA2 gene. These women were assessed for genetic risk at one of several genetic counseling programs for cancer in North America, Information about lifetime smoking history was derived from a questionnaire routinely administered to women who were found to carry a mutation in either gene. Smoking histories of case subjects with breast cancer and age-matched healthy control subjects were compared. Odds ratios for developing breast cancer were determined for smokers versus non-smokers by use of conditional logistic regression for matched sets after adjustment for other known risk factors. Results: Subjects with BRCA1 or BRCA2 gene mutations and breast cancer were significantly more likely to have been nonsmokers than were subjects with mutations and without breast cancer (two-sided P = .007). In a multivariate analysis, subjects with BRCA1 or BRCA2 mutations who had smoked cigarettes for more than 4 pack-years (i.e., number of packs per day multiplied by the number of years of smoking) were found to have a lower breast cancer risk (odds ratio = 0.46, 95% confidence interval = 0.27-0.80; two-sided P = .006) than subjects with mutations who never smoked. Conclusions: This study raises the possibility that smoking reduces the risk of breast cancer in carriers of BRCA1 or BRCA2 gene mutations. C1 Womens Coll Hosp, Ctr Res Womens Hlth, Dept Med, Toronto, ON M5G 1N8, Canada. Hotel Dieu, Epidemiol Res Unit, Res Ctr, Montreal, PQ, Canada. Univ Penn, Dept Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. Dana Farber Canc Inst, Div Canc Epidemiol & Control, Boston, MA 02115 USA. McGill Univ, Dept Med, Div Med Genet, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Univ Chicago, Dept Med, Canc Risk Clin, Chicago, IL 60637 USA. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. Duke Univ, Med Ctr, Dept Surg, Div Gynecol Oncol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. Int Agcy Res Canc, F-69372 Lyon, France. Creighton Univ, Sch Med, Dept Prevent Med & Publ Hlth, Omaha, NE USA. RP Narod, SA (reprint author), Womens Coll Hosp, Ctr Res Womens Hlth, Dept Med, 790 Bay St,Rm 750, Toronto, ON M5G 1N8, Canada. FU NCI NIH HHS [1RO1CA63678-01, CA57601, CA61231] NR 28 TC 93 Z9 96 U1 0 U2 3 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 MAY 20 PY 1998 VL 90 IS 10 BP 761 EP 766 DI 10.1093/jnci/90.10.761 PG 6 WC Oncology SC Oncology GA ZN919 UT WOS:000073696700011 PM 9605646 ER PT J AU Yamaguchi, T Olozak, I Chattopadhyay, N Butters, RR Kifor, O Scadden, DT Brown, EM AF Yamaguchi, T Olozak, I Chattopadhyay, N Butters, RR Kifor, O Scadden, DT Brown, EM TI Expression of extracellular calcium (Ca-o(2+))-sensing receptor in human peripheral blood monocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID OSTEOBLASTIC MC3T3-E1 CELLS; INTERLEUKIN-1; PROLIFERATION; OSTEOPOROSIS; RELEASE AB The calcium-sensing receptor (CaR) is a G protein-coupled receptor playing key roles in extracellular calcium ion (Ca-o(2+)) homeostasis in parathyroid gland and kidney. Macrophage-like mononuclear cells appear at sites of osteoclastic bone resorption during bone turnover and may play a role in the "reversal" phase of skeletal remodelling that follows osteoclastic resorption and precedes osteoblastic bone formation. Bone resorption produces substantial local increases in Ca-o(2+) that could provide a signal for such mononuclear cells present locally within the bone marrow microenvironment. Indeed, previous studies by other investigators have shown that raising Ca-o(2+) either in vivo or in vitro stimulated the release of interleukin-6 (IL-6) from human peripheral blood monocytes, suggesting that these cells express a Ca-o(2+)-sensing mechanism. In these earlier studies, however, the use of revel se transcription-polymerase chain reaction (RT-PCR) failed to detect transcripts for the CaR previously cloned from parathyroid and kidney in peripheral blood monocytes. Since we recently found that non specific esterase-positive, putative monocytes isolated from murine bone marrow express the CaR, we reevaluated the expression of this receptor in human peripheral blood monocytes. Immunocytochemistry, how cytometry, and Western blot analysis, performed using a polyclonal antiserum specific for the CaR, detected CaR protein in human monocytes. In addition, the use of RT-PCR with CaR-specific primers, followed by nucleotide sequencing of the amplified products, identified CaR transcripts in the cells. Therefore, taken together, our data show that human peripheral blood monocytes possess both CaR protein and mRNA very similar if not identical to those expressed in parathyroid and kidney that could mediate the previously described, direct effects of Ca-o(2+) on these cells. Furthermore, since mononuclear cells isolated from bone marrow also express the CaR, the latter might play some role in the "reversal" phase of bone remodelling, sensing local changes in Ca-o(2+) resulting from osteoclastic bone resorption and secreting osteotropic cytokines or performing other Ca-o(2+)-regulated functions that contribute to the control of bone turnover. (C) 1998 Academic Press. C1 Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Yamaguchi, T (reprint author), Brigham & Womens Hosp, Dept Med, Div Endocrine Hypertens, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK 50234] NR 16 TC 56 Z9 56 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 19 PY 1998 VL 246 IS 2 BP 501 EP 506 DI 10.1006/bbrc.1998.8648 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZP870 UT WOS:000073796900039 PM 9610391 ER PT J AU Kluwe, L MacCollin, M Tatagiba, M Thomas, S Hazim, W Haase, W Mautner, VF AF Kluwe, L MacCollin, M Tatagiba, M Thomas, S Hazim, W Haase, W Mautner, VF TI Phenotypic variability associated with 14 splice-site mutations in the NF2 gene SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE neurofibromatosis type 2; splice-site mutations; vestibular schwannomas; meningiomas; geno-phenotype correlation ID NEUROFIBROMATOSIS TYPE-2 GENE; GERM-LINE MUTATIONS; SPORADIC MENINGIOMAS; SOMATIC MUTATIONS; SCHWANNOMAS; IDENTIFICATION; ABNORMALITIES; FREQUENCY; SPECTRUM; SEVERITY AB Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder caused by mutations in the NF2 gene. Patients carrying NF2 mutations are predisposed to cerebral and spinal tumors with bilateral vestibular schwannomas as the hallmark. Using single strand conformation polymorphism and temperature gradient gel electrophoresis analysis, we have screened 87 unrelated NF2 patients for mutations in the NF2 gene. In this study, we report phenotypes associated with 14 splice-site mutations carried by 14 propositi and 11 relatives. The mutations were distributed in exons 2, 3, 5, 7, 8, 14, and 15. These splice-site mutations were associated with various phenotypes, from severe to asymptomatic. Phenotypic variation was also observed within families. Mutations downstream from exon 8 resulted more often in mild phenotypes. No meningiomas were found in any of 13 affected or mutation bearing individuals from three families with splice-site mutations of exons 14 and 15, These data suggest that splice-site alteration is a relatively common cause of NF2, and that unlike other mutations the clinical outcomes of splice-site mutations in the NF2 gene are variable. These results add to the growing body of information on genotype-phenotype correlation in NF2. (C) 1998 Wiley-Liss, Inc. C1 Univ Hamburg, Hosp Eppendorf, Dept Neurosurg, Lab Brain Tumor Biol, D-20246 Hamburg, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Hamburg, Hosp Eppendorf, Dept Ophthalmol, D-20246 Hamburg, Germany. Nordstadtkrankenhaus Hannover, Dept Neurosurg, Hannover, Germany. Gen Hosp Ochsenzoll, Dept Neurol, Hamburg, Germany. RP Kluwe, L (reprint author), Univ Hamburg, Hosp Eppendorf, Dept Neurosurg, Lab Brain Tumor Biol, Martinistr 52, D-20246 Hamburg, Germany. EM kluwe@uke.uni-hamburg.de NR 29 TC 51 Z9 52 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 18 PY 1998 VL 77 IS 3 BP 228 EP 233 DI 10.1002/(SICI)1096-8628(19980518)77:3<228::AID-AJMG8>3.0.CO;2-L PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZL219 UT WOS:000073410700008 PM 9605590 ER PT J AU Deboer, T Sanford, LD Ross, RJ Morrison, AR AF Deboer, T Sanford, LD Ross, RJ Morrison, AR TI Effects of electrical stimulation in the amygdala on ponto-geniculo-occipital waves in rats SO BRAIN RESEARCH LA English DT Article DE amygdala; electrical stimulation; PGO wave; rapid-eye-movement sleep; sleep ID SINGLE-UNIT-ACTIVITY; SLEEP-WAKING CYCLE; LOCUS COERULEUS; BEHAVING RATS; PGO SPIKES; ALBINO-RAT; NEURONS; AROUSAL; CATS; NUCLEUS AB We examined the role of the amygdala in the modulation of sleep and ponto-geniculo-occipital (PGO) waves in the rat. The amygdala projects massively, via its central nucleus, into brainstem regions involved in alerting and in the generation of rapid-eye movement (REM) sleep and PGO waves. Electrical stimulation of the central nucleus of the amygdala during REM sleep increased PGO wave amplitude. Stimulation during non-REM sleep decreased PGO wave frequency. The results indicate that the amygdala has a role in modulating brainstem neural mechanisms underlying alerting during sleep. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Univ Penn, Sch Vet Med, Dept Anim Biol, Lab Study Brain Sleep, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Sanford, LD (reprint author), Univ Penn, Sch Vet Med, Dept Anim Biol, Lab Study Brain Sleep, 3800 Spruce St, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [MH42903]; NINDS NIH HHS [NS35281] NR 39 TC 33 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 18 PY 1998 VL 793 IS 1-2 BP 305 EP 310 DI 10.1016/S0006-8993(98)00178-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA ZX807 UT WOS:000074557400034 PM 9630691 ER PT J AU Lloyd-Jones, D Camargo, CA Lapuerta, P Giugliano, RP O'Donnell, CJ AF Lloyd-Jones, D Camargo, CA Lapuerta, P Giugliano, RP O'Donnell, CJ TI Electrocardiographic and clinical predictors of acute myocardial infarction in patients with unstable angina pectoris SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; RISK STRATIFICATION; DEPRESSION; MECHANISMS; PROGNOSIS AB Among patients with unstable angina pectoris (UAP), those who have non-ST-elevatian acute myocardial infarction (AMI) are at higher risk for subsequent adverse events. To determine predictors of AMI in patients with UAP, we studied consecutive nonreferral patients with UAP or AMI admitted from the emergency department to the intensive care or telemetry units of an urban teaching hospital over 1 year. There were 280 study patients (mean age 66 years, 1/3 women); 24% had AMI at presentation, whereas 76% had UAP without evidence of AMI. Thresholds of greater than or equal to 3 involved leads (odds ratio [OR] 3.3; 95% confidence intervals [CI] 1.6 to 6.9) and greater than or equal to 0.2 mV (OR 5.1; 95% CI 2.2 to 11.6) of ST depression on the presenting electrocardiogram were strongly associated with AMI. The multivariate predictors of AMI were reported duration of symptoms > 4 hours (OR 3.8; 95% CI 1.9 to 7.3), absence of prior revascularization (OR 3.5; 95% CI 1.6 to 7.5), absence of beta-blocker use before presentation (OR 2.8; 95% CI 1.3 to 5.8), and presence of new ST depression (OR 2.8; 95% CI 1.4 to 5.7). Using the 4 multivariate predictors, a prediction rule was developed. The percentages of patients with AMI when 0, 1, 2, 3, or 4 characteristics were present, respectively, were 7%, 6%, 24%, 46%, and 83% (p < 0.001). A similar prediction rule developed from the Thrombolysis in Myocardial Ischemia ill trial was validated in our cohort. Among patients with UAP, electrocardiographic and clinical variables can help immediately identify those at high risk for AMI at presentation. (C) 1998 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Univ So Calif, Sch Med, Div Gen Internal Med, Los Angeles, CA USA. RP Lloyd-Jones, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [HL-03533, HL-07575] NR 21 TC 42 Z9 42 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 1998 VL 81 IS 10 BP 1182 EP 1186 DI 10.1016/S0002-9149(98)00155-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN230 UT WOS:000073622900003 PM 9604942 ER PT J AU Stadius, ML Lehmann, KG AF Stadius, ML Lehmann, KG TI Structural constriction of the artery wall contributes to stenosis severity in unstable angina SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY; WOUND CONTRACTION; DISEASE AB Eight consecutive patients with unstable angina underwent intravascular ultrasound imaging of the culprit artery with measurements recorded at the stenosis and at an adjacent reference site. In all patients, total artery cross-sectional area was smaller at the stenosis site than at the reference site, indicating that a structural change in the artery wall due to a constrictive process appears to contribute to the worsening of stenosis severity associated with unstable angina. C1 Vet Adm Med Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Stadius, ML (reprint author), Vet Adm Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 1998 VL 81 IS 10 BP 1196 EP + DI 10.1016/S0002-9149(98)00088-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN230 UT WOS:000073622900005 PM 9604944 ER PT J AU Alyea, EP Soiffer, RJ Canning, C Neuberg, D Schlossman, R Pickett, C Collins, H Wang, YL Anderson, KC Ritz, J AF Alyea, EP Soiffer, RJ Canning, C Neuberg, D Schlossman, R Pickett, C Collins, H Wang, YL Anderson, KC Ritz, J TI Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; ADOPTIVE IMMUNOTHERAPY; SELECTIVE DEPLETION; T-CELLS; LEUKOCYTE TRANSFUSIONS; PREVENTION; CD8+; RECOGNITION AB Donor lymphocyte infusions (DLI) can induce remissions in patients who have relapsed after allogeneic bone marrow transplantation (BMT). However, DLI frequently also result in significant acute and/or chronic graft-versus-host disease (GVHD). Several clinical and experimental lines of evidence have suggested that CD8(+) T cells play a critical role in the pathogenesis of GVHD. To develop methods to reduce the incidence of GVHD associated with DLI, we administered defined numbers of CD4(+) donor T cells after ex vivo depletion of CD8(+) lymphocytes to 40 patients with relapsed hematologic malignancies after allogeneic BMT Cohorts of patients received 0.3, 1.0, or 1.5 x 10(8) CD4(+) cells/kg. Overall, 12 of 38 patients (32%) evaluable for toxicity developed acute or chronic GVHD. However, 6 of 27 patients (22%) receiving 0.3 x 10(8) CD4 cells/kg developed GVHD compared with 6 of 11 patients (55%) who received greater than or equal to 1.0 x 10(8) CD4 cells/kg (P = .07). Treatment-related mortality was low (3%), with 1 death related to infection in the setting of immunosuppression for GVHD. Disease responses after CD4(+) DLI were documented in 15 of 19 patients (79%) with early-phase chronic myelogenous leukemia (CML) relapse, 5 of 6 patients (83%) with relapsed multiple myeloma, and 1 patient with myelodysplasia. For patients with early-phase CML relapse, the Kaplan-Meier probability of achieving complete cytogenetic remission was 87% and the probability of complete molecular response was 78% at 1 year after DLI. The median time to complete cytogenetic response and molecular response in patients with CML was 13 weeks (range, 9 to 30 weeks) and 34 weeks (range, 10 to 56 weeks), respectively. The median time to response in patients with multiple myeloma was 26 weeks (range, 15 to 62 weeks). All patients in this trial who developed GVHD demonstrated tumor regression, but the presence of GVHD was not required for patients to achieve a response, because 48% of responding patients never developed evidence of GVHD. Two patients with CML who did not respond at dose level 1 subsequently achieved complete cytogenetic remission after a second infusion of CD8-depleted cells at dose level 2. In patients with evidence of mixed hematopoietic chimerism who achieved a complete remission after DLI, cytogenetic analysis of marrow cells also demonstrated conversion to complete donor hematopoiesis in all evaluable patients. These studies suggest that relatively low numbers of CD8-depleted donor lymphocytes are effective in inducing complete remissions in patients with stable-phase CML and multiple myeloma who have relapsed after allogeneic BMT. Because of the relatively low risk of toxicity associated with the infusion of defined numbers of CD4(+) donor cells, further studies can be undertaken in the setting of persistent minimal residual disease to prevent relapse after allogeneic BMT. (C) 1998 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. RP Alyea, EP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA01730]; NIAID NIH HHS [AI29530] NR 51 TC 222 Z9 229 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1998 VL 91 IS 10 BP 3671 EP 3680 PG 10 WC Hematology SC Hematology GA ZM210 UT WOS:000073515700016 PM 9573003 ER PT J AU Shimizu, Y Ogawa, M Kobayashi, M Almeida-Porada, G Zanjani, ED AF Shimizu, Y Ogawa, M Kobayashi, M Almeida-Porada, G Zanjani, ED TI Engraftment of cultured human hematopoietic cells in sheep SO BLOOD LA English DT Article ID EX-VIVO EXPANSION; MURINE MARROW-CELLS; STEM-CELLS; PROGENITOR CELLS; EXVIVO EXPANSION; TRANSPLANTATION; MAINTENANCE; ABILITY; IL-3; ERYTHROPOIETIN AB In an effort to expand human hematopoietic progenitors and stem cells in vitro, we cultured human CD34(+)c-kit(low) bone marrow cells in suspension in the presence of KIT ligand, FLK2/FLT3 ligand, interleukin-6 (IL-6), and erythropoietin with or without IL-3 and tested their engrafting capabilities by injecting them into sheep fetuses. As markers for engraftment, we analyzed CD45(+) cells and karyotypes of the colonies grown in methylcellulose culture. In three separate experiments, day-60 engraftment in the bone marrow was seen with both fresh cells and cells cultured in the presence or absence of IL-3. When fetuses were allowed to be born and analyzed for CD45(+) cells, no long-term engraftment was seen with cultured cells. We then pooled the CD45(+) cells of the fetal samples and transplanted them into secondary recipient fetuses. Day-60 engraftment in the secondary recipients was again noted when transplantation in the primary recipients was initiated with fresh cells. There were 3 cases in which cultured cells showed signs of engraftment in the secondary recipients, but the remaining 24 cases showed no signs of engraftment. These data documented that suspension culture for 2 weeks of enriched adult human bone marrow cells can maintain short-term (2 months) engrafting cells, but may not maintain longer term engrafting cells. This sheep/human xenograft model may serve as an excellent method for the evaluation of the engraftment potential of in vitro-expanded cells. (C) 1998 by The American Society of Hematology. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Dept Vet Affairs Med Ctr, Charleston, SC USA. Dept Vet Affairs Med Ctr, Reno, NV USA. RP Ogawa, M (reprint author), Ralph H Johnson Dept Vet Affairs Hosp, 109 Bee St, Charleston, SC 29401 USA. FU NHLBI NIH HHS [HL 48714]; NIDDK NIH HHS [DK 32294, DK 48714] NR 28 TC 44 Z9 47 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 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1998 VL 91 IS 10 BP 3688 EP 3692 PG 5 WC Hematology SC Hematology GA ZM210 UT WOS:000073515700018 PM 9573005 ER PT J AU Thompson, MA Ransom, DG Pratt, SJ MacLennan, H Kieran, MW Detrich, HW Vail, B Huber, TL Paw, B Brownlie, AJ Oates, AC Fritz, A Gates, MA Amores, A Bahary, N Talbot, WS Her, H Beier, DR Postlethwait, JH Zon, LI AF Thompson, MA Ransom, DG Pratt, SJ MacLennan, H Kieran, MW Detrich, HW Vail, B Huber, TL Paw, B Brownlie, AJ Oates, AC Fritz, A Gates, MA Amores, A Bahary, N Talbot, WS Her, H Beier, DR Postlethwait, JH Zon, LI TI The cloche and spadetail genes differentially affect hematopoiesis and vasculogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE zebrafish; hematopoiesis; blood; Danio rerio ID TRANSCRIPTION FACTOR GATA-2; YOLK-SAC; CARDIOVASCULAR DEVELOPMENT; EMBRYONIC-DEVELOPMENT; XENOPUS-LAEVIS; CELL LINEAGES; MICE LACKING; STEM-CELLS; FATE MAP; C-MYB AB In vertebrates, hematopoietic and vascular progenitors develop from ventral mesoderm. The first primitive wave of hematopoiesis yields embryonic red blood cells, whereas progenitor cells of subsequent definitive waves form all hematopoietic cell Lineages. In this report we examine the development of hematopoietic and vasculogenic cells in normal zebrafish and characterize defects in cloche and spadetail mutant embryos. The zebrafish homologs of lmo2, c-myb, fli1, flk1, and flt4 have been cloned and characterized in this study. Expression of these genes identifies embryonic regions that contain hematopoietic and vascular progenitor cells. The expression of c-myb also identifies definitive hematopoietic cells in the ventral wall of the dorsal aorta. Analysis of b316 mutant embryos that carry a deletion of the c-myb gene demonstrates that c-myb is not required for primitive erythropoiesis in zebrafish even though it is expressed in these cells. Both cloche and spadetail mutant embryos have defects in primitive hematopoiesis and definitive hematopoiesis. The cloche mutants also have significant decreases in vascular gene expression, whereas spadetail mutants expressed normal levels of these genes. These studies demonstrate that the molecular mechanisms that regulate hematopoiesis and vasculogenesis have been conserved throughout vertebrate evolution and the clo and spt genes are key regulators of these programs. (C) 1998 Academic Press. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Northeastern Univ, Dept Biol, Boston, MA 02115 USA. Royal Melbourne Hosp, Ludwig Inst Canc Res, Cytokine Biol Lab, Melbourne, Vic 3050, Australia. Univ Oregon, Dept Biol, Eugene, OR 97403 USA. NYU, Med Ctr, Skirball Inst, Dev Genet Program, New York, NY 10016 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Zon, LI (reprint author), Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM zon@rascal.med.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU NHLBI NIH HHS [HL09773, HL48801]; NIDDK NIH HHS [DK49216] NR 55 TC 351 Z9 358 U1 1 U2 11 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 15 PY 1998 VL 197 IS 2 BP 248 EP 269 DI 10.1006/dbio.1998.8887 PG 22 WC Developmental Biology SC Developmental Biology GA ZT234 UT WOS:000074064000009 PM 9630750 ER PT J AU Noirot, P Kolodner, RD AF Noirot, P Kolodner, RD TI DNA strand invasion promoted by Escherichia coli RecT protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HOMOLOGOUS RECOMBINATION; GENETIC-RECOMBINATION; BREAK REPAIR; INTRAMOLECULAR RECOMBINATION; EXONUCLEASE; EXCHANGE; IDENTIFICATION; REPLICATION; MUTATIONS; BINDING AB The RecT protein of Escherichia coli is a DNA-pairing protein required for the RecA-independent recombination events promoted by the RecE pathway. The RecT protein was found to bind to both single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in the absence of Mg2+. In the presence of Mg2+, RecT binding to dsDNA was inhibited drastically, whereas binding to ssDNA was inhibited only to a small extent. RecT promoted the transfer of a single-stranded oligonucleotide into a supercoiled homologous duplex to form a D (displacement)-loop. D-loop formation occurred in the absence of Mg2+ and at 1 mM Mg2+ but was inhibited by increasing concentrations of Mg2+ and did not require a high energy cofactor. Strand transfer was mediated by a RecT-ssDNA nucleoprotein complex reacting with a naked duplex DNA and was prevented by the formation of RecT-dsDNA nucleoprotein complexes. Finally, RecT mediated the formation of joint molecules between a supercoiled DNA and a linear dsDNA substrate with homologous 3'-single-stranded tails. Together these results indicate that RecT is not a helix-destabilizing protein promoting a reannealing reaction but rather is a novel type of pairing protein capable of promoting recombination by a DNA strand invasion mechanism. These results are consistent with the observation that RecE (exonuclease VIII) and RecT can promote RecA-independent double-strand break repair in E. coli. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Human Canc Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Kolodner, RD (reprint author), INRA, CRJJ, F-78352 Jouy En Josas, France. FU NIGMS NIH HHS [GM26017] NR 41 TC 50 Z9 50 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 1998 VL 273 IS 20 BP 12274 EP 12280 DI 10.1074/jbc.273.20.12274 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZN277 UT WOS:000073629800043 PM 9575178 ER PT J AU Matthews, JB Hassan, I Meng, SF Archer, SY Hrnjez, BJ Hodin, RA AF Matthews, JB Hassan, I Meng, SF Archer, SY Hrnjez, BJ Hodin, RA TI Na-K-2Cl cotransporter gene expression and function during enterocyte differentiation - Modulation of Cl(-) secretory capacity by butyrate SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE intestinal mucosa; fatty acids; colitis; bumetanide; cystic fibrosis transmembrane conductance regulator ID TRANSMEMBRANE CONDUCTANCE REGULATOR; INTESTINAL EPITHELIAL-CELLS; CYSTIC-FIBROSIS; MESSENGER-RNA; HT-29 CELLS; CELLULAR-DIFFERENTIATION; ELECTROLYTE TRANSPORT; MOLECULAR-CLONING; SODIUM-BUTYRATE; RAT INTESTINE AB The basolateral Na-K-2Cl cotransporter (NKCC1) is a key component of the intestinal crypt cell secretory apparatus. Its fate during the transition to absorptive enterocyte and the potential impact of its altered expression on secretory output have not been addressed. In this report, NKCC1 mRNA was found to be expressed in rat jejunal crypt but not villus cells. Butyrate treatment of intestinal epithelial HT29 cells induced a differentiation pattern that recapitulated the rat intestinal crypt-villus axis, with NKCC1 mRNA levels decreasing in a time-and dose-dependent fashion in parallel with upregulation of apical brush-border markers. Butyrate but not acetate or proprionate decreased basal and cAMP-stimulated bumetanide-sensitive K(+) ((86)Rb) uptake in both HT29 cells and the Cl(-)-secreting T84 line. Butyrate markedly decreased transepithelial Cl(-) secretion in confluent T84 monolayers without effect on cAMP-regulated apical Cl(-) efflux. We conclude that NKCC1 regulation during enterocyte differentiation occurs at the level of gene expression, and that selective downregulation of NKCC1 gene expression and function by butyrate leads to a profound decrease in transepithelial Cl(-) secretion. These data emphasize the importance of NKCC1 in determining epithelial secretory capacity and suggest the possibility of modulation of the enterocytic transport phenotype as therapy for diarrheal disorders. C1 Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Matthews, JB (reprint author), Beth Israel Deaconess Med Ctr, Dept Surg, Div Gen Surg, 330 Brookline Ave,East Campus, Boston, MA 02215 USA. EM jmatthew@bidmc.harvard.edu FU NIDDK NIH HHS [DK-47186, DK-48010, DK-51630] NR 52 TC 56 Z9 56 U1 0 U2 2 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 MAY 15 PY 1998 VL 101 IS 10 BP 2072 EP 2079 DI 10.1172/JCI1042 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZP981 UT WOS:000073808800006 PM 9593763 ER PT J AU Pontoglio, M Sreenan, S Roe, M Pugh, W Ostrega, D Doyen, A Pick, AJ Baldwin, A Velho, G Froguel, P Levisetti, M Bonner-Weir, S Bell, GI Yaniv, M Polonsky, KS AF Pontoglio, M Sreenan, S Roe, M Pugh, W Ostrega, D Doyen, A Pick, AJ Baldwin, A Velho, G Froguel, P Levisetti, M Bonner-Weir, S Bell, GI Yaniv, M Polonsky, KS TI Defective insulin secretion in hepatocyte nuclear factor 1 alpha-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE diabetes; insulin secretion; hepatocyte nuclear factor 1 alpha; maturity-onset diabetes of the young; beta cell ID BETA-CELL MASS; ALBUMIN GENE; GLUCOSE; EXPRESSION; MUTATIONS; GROWTH; MODY3; RAT AB Mutations in the gene for the transcription factor hepatocyte nuclear factor (HNF) 1 alpha cause maturity-onset diabetes of the young (MODY) 3, a form of diabetes that results from defects in insulin secretion. Since the nature of these defects has not been defined, we compared insulin secretory function in heterozygous [HNF-1 alpha (+/-)] or homozygous [HNF-1 alpha (-/-)] mice with null mutations in the HNF-1 alpha gene with their wild-type littermates [HNF-1 alpha (+/+)]. Blood glucose concentrations were similar in HNF-1 alpha (+/+) and (+/-) mice (7.8+/-0.2 and 7.9+/-0.3 mM), but were significantly higher in the HNF-1 alpha (-/-) mice (13.1+/-0.7 mM, P < 0.001). Insulin secretory responses to glucose and arginine in the perfused pancreas and perifused islets from HNF-1 alpha( (-/-) mice were < 15% of the values in the other two groups and were associated with similar reductions in intracellular Ca2+ responses, These defects were not due to a decrease in glucokinase or insulin gene transcription. P cell mass adjusted for body weight was not reduced in the (-/-) animals, although pancreatic insulin content adjusted for pancreas weight was slightly lower (0.06+/-0.01 vs. 0.10+/-0.01 mu g/mg, P < 0.01) than in the (+/+) animals. In summary, a null mutation in the HNF-1 alpha gene in homozygous mice leads to diabetes due to alterations in the pathways that regulate beta cell responses to secretagogues including glucose and arginine, These results provide further evidence in support of a key role for HNF-1 alpha in the maintenance of normal beta cell function. C1 Univ Chicago, Pritzker Sch Med, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Howard Hughes Med Inst, Chicago, IL 60637 USA. Inst Pasteur, CNRS, Unite Rech Associee 1644, Dept Biotechnol, F-75015 Paris, France. Joslin Diabet Ctr, Boston, MA 02215 USA. Hop St Vincent de Paul, INSERM, U342, F-75014 Paris, France. Inst Pasteur, F-59019 Lille, France. RP Polonsky, KS (reprint author), Univ Chicago, Pritzker Sch Med, Dept Med, 5841 S Maryland Ave,MC 1027, Chicago, IL 60637 USA. FU NIDDK NIH HHS [DK-31842, DK-44840, DK-20595] NR 22 TC 223 Z9 226 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 15 PY 1998 VL 101 IS 10 BP 2215 EP 2222 DI 10.1172/JCI2548 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZP981 UT WOS:000073808800020 PM 9593777 ER PT J AU Brandon, EP Logue, SF Adams, MR Qi, M Sullivan, SP Matsumoto, AM Dorsa, DM Wehner, JM McKnight, GS Idzerda, RL AF Brandon, EP Logue, SF Adams, MR Qi, M Sullivan, SP Matsumoto, AM Dorsa, DM Wehner, JM McKnight, GS Idzerda, RL TI Defective motor behavior and neural gene expression in RII beta protein kinase A mutant mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cAMP-dependent protein kinase; PKA; knockout; mouse; striatum; dopamine; amphetamine; locomotion; rotarod; sensitization; fos; dynorphin ID RAT STRIATAL NEURONS; REGULATORY SUBUNIT; MESSENGER-RNA; NUCLEUS-ACCUMBENS; BASAL GANGLIA; C-FOS; TARGETED DISRUPTION; DOPAMINE-RECEPTORS; PRODYNORPHIN GENE; AGED RATS AB Motor behavior is modulated by dopamine-responsive neurons in the striatum, where dopaminergic signaling uses G-protein-coupled pathways, including those that result in the activation of cAMP-dependent protein kinase (PKA). The RII beta isoform of PKA is highly enriched in the striatum, and targeted disruption of the RII beta gene in mice leads to a dramatic reduction in total PKA activity in this region. Although the mutant mice show typical locomotor responses after acute administration of dopaminergic drugs, they display abnormalities in two experience-dependent locomotor behaviors: training on the rotarod task and locomotor sensitization to amphetamine. In addition, amphetamine induction of fos is absent, and the basal expression of dynorphin mRNA is reduced in the striatum. These results demonstrate that motor learning and the regulation of neuronal gene expression require RII beta PKA, whereas the acute locomotor effects of dopaminergic drugs are relatively unaffected by this PKA deficiency. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Pharmacol, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. RP Univ Washington, Dept Pharmacol, Box 356650, Seattle, WA 98195 USA. FU NIAAA NIH HHS [AA-00141]; NIDA NIH HHS [DA-10156]; NIGMS NIH HHS [GM-07108] NR 74 TC 107 Z9 107 U1 3 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 15 PY 1998 VL 18 IS 10 BP 3639 EP 3649 PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZL895 UT WOS:000073484300016 PM 9570795 ER PT J AU Namura, S Zhu, JM Fink, K Endres, M Srinivasan, A Tomaselli, KJ Yuan, JY Moskowitz, MA AF Namura, S Zhu, JM Fink, K Endres, M Srinivasan, A Tomaselli, KJ Yuan, JY Moskowitz, MA TI Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ischemia; caspase; CED-3/ICE proteases; mouse brain; apoptosis; caspase-3 cleavage; caspase-like enzyme activity; TUNEL; CNS development ID PROGRAMMED CELL-DEATH; INTERLEUKIN-1-BETA CONVERTING-ENZYME; DNA FRAGMENTATION; ICE/CED-3 PROTEASE; CYSTEINE PROTEASE; GENETIC-CONTROL; MICE DEFICIENT; NEURONAL DEATH; C-ELEGANS; CED-3 AB We examined the expression, activation, and cellular localization of caspase-3 (CPP32) using immunohistochemistry, immunoblots, and cleavage of the fluorogenic substrate N-benzyloxycarbonyl-Asp-Glu-Val-Asp-7-amino-4-trifluoromethyl methyl coumarin (zDEVD-afc) in adult mouse brain after temporary (2 hr) middle cerebral artery occlusion produced by filament insertion into the carotid artery. Immunoreactive caspase-3p32 but not its cleavage product caspase-3p20 was constitutively expressed in neurons throughout brain and was most prominent in neuronal perikarya within piriform cortex. Caspase-like enzyme activity was elevated in brain homogenate 0-3 hr after reperfusion and reached a peak within 30 to 60 min. Caspase-3p20 immunoreactivity became prominent in neuronal perikarya within the middle cerebral artery territory at the time of reperfusion and on immunoblots 1-12 hr later. DNA laddering (agarose gels) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL)stained cells were detected 6-24 hr after reperfusion, At 12-24 hr, immunoreactive p20 was visualized in TUNEL-positive cells, a finding also observed in apoptotic mouse cerebellar granule cells on postnatal day 5. Together, these observations suggest the existence of a time-dependent evolution of ischemic injury characterized by the close correspondence between caspase-like enzyme activation and an associated increase in immunoreactive product (caspase-3p20) beginning at or before reperfusion and followed several hours later by morphological and biochemical features of apoptosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. IDUN Pharmaceut Inc, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Neurosurg Serv, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS10828] NR 51 TC 657 Z9 688 U1 4 U2 26 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 15 PY 1998 VL 18 IS 10 BP 3659 EP 3668 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZL895 UT WOS:000073484300018 PM 9570797 ER PT J AU Walsh, EJ McGee, J McFadden, SL Liberman, MC AF Walsh, EJ McGee, J McFadden, SL Liberman, MC TI Long-term effects of sectioning the olivocochlear bundle in neonatal cats SO JOURNAL OF NEUROSCIENCE LA English DT Article DE efferent; olivocochlear; cochlea; development; superior olivary complex; hearing; auditory; deefferentation ID OUTER HAIR-CELLS; PERIPHERAL AUDITORY NEURONS; TEMPORARY THRESHOLD SHIFTS; COCHLEAR DE-EFFERENTATION; GUINEA-PIG COCHLEA; POSTNATAL-DEVELOPMENT; NERVE-FIBERS; 2-TONE STIMULI; TUNING CURVES; ELECTRICAL-STIMULATION AB The olivocochlear bundle (OCB) was cut in neonatal cats to evaluate its role in the development of normal cochlear function. Approximately 1 year after deefferentation, acute auditory nerve fiber (ANF) recordings were made from lesioned animals, lesion shams, and normal controls. The degree of deefferentation was quantified via light microscopic evaluation of the density of OCB fascicles in the tunnel of Corti, and selected cases were analyzed via electron microscopy. In the most successful cases, the deefferentation was virtually complete. ANFs from successfully lesioned animals exhibited significant pathophysiology compared with normals and with other animals in which the surgery failed to interrupt the OCB. Thresholds at the characteristic frequency (CF), the frequency at which ANFs are most sensitive, were elevated across the CF range, with maximal effects for CFs in the 10 kHz region. Frequency threshold or tuning curves displayed reduction of tip-to-tail ratios (the difference between CF and low-frequency "tail" thresholds) and decreased sharpness of tuning. These pathological changes are generally associated with outer hair cell (OHC) damage. However, light microscopic histological analysis showed minimal hair cell loss and no significant differences between normal and deefferented groups. Spontaneous discharge rates (SRs) were lower than normal; however, those fibers with the highest SRs remained more sensitive than those with lower SRs. Findings suggest that the interaction between OC efferents and OHCs early in development may be critical for full expression of active mechanical processes. C1 Boys Town Natl Res Hosp, Dev Auditory Physiol Lab, Omaha, NE 68131 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Walsh, EJ (reprint author), Boys Town Natl Res Hosp, Dev Auditory Physiol Lab, 555 N 30th St, Omaha, NE 68131 USA. FU NIDCD NIH HHS [DC00034, DC00188, DC00215] NR 100 TC 92 Z9 94 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 15 PY 1998 VL 18 IS 10 BP 3859 EP 3869 PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZL895 UT WOS:000073484300036 PM 9570815 ER PT J AU Kelly, K AF Kelly, K TI Peace & war: Reminiscences of a life on the frontiers of science. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp, Treadwell Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD MAY 15 PY 1998 VL 123 IS 9 BP 108 EP 108 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA ZN720 UT WOS:000073674900189 ER PT J AU van Orsouw, NJ Dhanda, RK Rines, RD Smith, WM Sigalas, I Eng, C Vijg, J AF van Orsouw, NJ Dhanda, RK Rines, RD Smith, WM Sigalas, I Eng, C Vijg, J TI Rapid design of denaturing gradient-based two-dimensional electrophoretic gene mutational scanning tests SO NUCLEIC ACIDS RESEARCH LA English DT Article ID STRAND CONFORMATION POLYMORPHISM; GEL-ELECTROPHORESIS; DNA FRAGMENTS; GC-CLAMP; SINGLE; SUBSTITUTIONS; CLEAVAGE; SEQUENCE; ARRAYS; LONG AB With the current rapid pace at which human disease genes are identified there is a need for practical, cost-efficient genetic screening tests. Two-dimensional electrophoretic separation of PCR-amplified gene fragments on the basis of size and base pair sequence, in non-denaturing and denaturing gradient polyacrylamide gels respectively, provides a rapid parallel approach to gene mutational scanning. Accuracy of the denaturing gradient gel electrophoresis (DGGE) component of this system strongly depends on the design of the PCR primers and the melting characteristics of the fragments they encompass. We have developed a fully automated generally applicable procedure to generate optimal two-dimensional test designs at a minimum amount of time and effort. Designs were generated for the RB1, TP53, MLH1 and BRCA1 genes that can be readily implemented in research and clinical laboratories as low cost genetic screening tests. C1 Beth Israel Deaconess Med Ctr, Dept Med, Gerontol Div, Mol Genet Sect, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Human Canc Genet Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP van Orsouw, NJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Gerontol Div, Mol Genet Sect, Boston, MA 02115 USA. EM nvanorso@bidmc.harvard.edu OI Eng, Charis/0000-0002-3693-5145 FU NIA NIH HHS [1P30AG13314-01] NR 30 TC 26 Z9 27 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 15 PY 1998 VL 26 IS 10 BP 2398 EP 2406 DI 10.1093/nar/26.10.2398 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZP804 UT WOS:000073790100021 PM 9580692 ER PT J AU Li, N Oberley, TD Oberley, LW Zhong, WX AF Li, N Oberley, TD Oberley, LW Zhong, WX TI Overexpression of manganese superoxide dismutase in DU145 human prostate carcinoma cells has multiple effects on cell phenotype SO PROSTATE LA English DT Article DE reactive oxygen species; mitochondria; redox ID GLUTATHIONE-PEROXIDASE-ACTIVITY; ANTIOXIDANT ENZYMES; CU,ZN-SUPEROXIDE DISMUTASE; PARAQUAT RESISTANCE; HAMSTER-KIDNEY; FREE-RADICALS; RAT-LIVER; EXPRESSION; RADIATION; GROWTH AB BACKGROUND. Recent studies suggest that the gene for manganese superoxide dismutase (MnSOD) is a candidate turner-suppressor gene. The present study was designed to study the effect of overexpression of MnSOD on cultured human prostate carcinoma cells. METHODS. DU145 human prostate carcinoma cells were transfected with the cDNA for manganese superoxide dismutase (MnSOD), and two clones overexpressing MnSOD activity were subsequently characterized by comparison with parental and plasmid control-transfected cells. RESULTS. One clone overexpressing MnSOD had no change in other antioxidant enzymes (AEs) (nonadapted), while a second clone showed an increase in catalase activity (adapted). Sensitivity of parental, plasmid control-transfected, and MnSOD cDNA-transfected cells to agents that generate oxidative stress correlated with AE profiles. Both clones overexpressing MnSOD activity showed increased reactive oxygen species levels under basal cell culture conditions. Both clones overexpressing MnSOD activity showed inhibition of cell growth in vitro and in vivo compared with parental and plasmid control-transfected cells. Flow cytometry studies using mitochondrial-specific probes showed equal mitochondrial mass in all cell lines, but altered mitochondrial membrane potential in MnSOD-overexpressing clones compared with parental or plasmid control-transfected cells. CONCLUSIONS. Our results suggest novel mechanisms by which MnSOD overexpression may modulate the malignant phenotype, with potential applications in developing new therapies for prostate cancer. (C) 1998 Wiley-Liss, Inc. C1 William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI USA. Univ Iowa, Radiat Res Lab, Iowa City, IA 52242 USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. FU NCI NIH HHS [CA 41267] NR 50 TC 123 Z9 126 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD MAY 15 PY 1998 VL 35 IS 3 BP 221 EP 233 DI 10.1002/(SICI)1097-0045(19980515)35:3<221::AID-PROS8>3.0.CO;2-J PG 13 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA ZL815 UT WOS:000073474300008 PM 9582091 ER PT J AU Di Cunto, F Topley, G Calautti, E Hsiao, J Ong, L Seth, PK Dotto, GP AF Di Cunto, F Topley, G Calautti, E Hsiao, J Ong, L Seth, PK Dotto, GP TI Inhibitory function of p21(Cip1/WAF1) in differentiation of primary mouse keratinocytes independent of cell cycle control SO SCIENCE LA English DT Article ID P21(WAF1/CIP1) EXPRESSION; TERMINAL DIFFERENTIATION; GROWTH; P21; PROTEIN; PROGRESSION; WAF1/CIP1; CALCIUM; PCNA AB The cyclin-dependent kinase inhibitor p21(Cip1/WAF1) has been implicated as an inducer of differentiation. However, although expression of p21 is increased in postmitotic cells immediately adjacent to the proliferative compartment, its expression is decreased in cells further along the differentiation program. Expression of the p21 protein was decreased in terminally differentiated primary keratinocytes of mice, and this occurred by a proteasome-dependent pathway. Forced expression of p21 in these cells inhibited the expression of markers of terminal differentiation at both the protein and messenger RNA levels. These inhibitory effects on differentiation were not observed with a carboxyl-terminal truncation mutant or with the unrelated cyclin-dependent kinase inhibitor p16(INK4a), although all these molecules exerted similar inhibition of cell growth. These findings reveal an inhibitory role of p21 in the late stages of differentiation that does not result from the effects of p21 on the cell cycle. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Turin, Dept Genet Biol & Med Chem, Torino, Italy. NCI, Med Branch, Breast Canc Sect, Bethesda, MD 20892 USA. RP Dotto, GP (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 13th St, Charlestown, MA 02129 USA. EM Paolo_Dotto@cbrc.mgh.harvard.edu OI CALAUTTI, Vincenzo/0000-0002-4439-9709; di cunto, ferdinando/0000-0001-9367-6357 FU NCI NIH HHS [CA16038]; NIAMS NIH HHS [AR39190] NR 24 TC 222 Z9 224 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 15 PY 1998 VL 280 IS 5366 BP 1069 EP 1072 DI 10.1126/science.280.5366.1069 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZN615 UT WOS:000073663600045 PM 9582119 ER PT J AU Rosen, HR Gretch, DR Oehlke, M Flora, KD Benner, KG Rabkin, JM Corless, CL AF Rosen, HR Gretch, DR Oehlke, M Flora, KD Benner, KG Rabkin, JM Corless, CL TI Timing and severity of initial hepatitis C recurrence as predictors of long-term liver allograft injury SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 08-15, 1996 CL CHICAGO, ILLINOIS SP Amer Assoc Study Liver Dis ID VIRUS-INFECTION; TRANSPLANT RECIPIENTS; MAJOR GENOTYPES; CLASSIFICATION; QUANTITATION; FEATURES; SUBTYPES; REGION AB Background. The majority of patients infected with hepatitis C virus (HCV) undergoing liver transplantation develop evidence of histologic recurrence, and multiple mechanisms are likely poised to affect long-term allograft injury, The purpose of this analysis was to study the hypothesis that histologic and biochemical features at the onset of HCV recurrence predict the long-term evolution of allograft hepatitis. Methods. We studied 34 consecutive liver transplant recipients with evidence of histologic HCV recurrence and with a minimal histologic follow-up of 1 year (up to 6.2 years; mean: 696+/-83.2 days), Two-hundred and seventy-eight serial allograft biopsies (mean: 6.85+/-0.62 per patient, range: 4-21) were analyzed. The hepatic activity index was utilized to quantitate piecemeal necrosis, intralobular degeneration, portal inflammation, and hepatic fibrosis, The presence of hepatocyte ballooning degeneration and cholestasis was also assessed. Results, Although there was no significant difference with regard to initial hepatic activity index scores between patients who ultimately developed allograft cirrhosis (group 1; n=8) versus those with milder hepatitis (group 2; n=26), the finding of ballooning degeneration/cholestasis was more frequent in the former group (P=0.04), The distribution of HCV genotypes, the mean follow-up after orthotopic liver transplantation, the mean number of allograft biopsy specimens per patient, basal immunosuppression, and incidence of rejection were comparable in both groups, Patients who ultimately developed allograft cirrhosis had significantly higher initial total bilirubin at the onset of histologic recurrence and peak total bilirubin (pT.Bili, the highest value in the ensuing month). Actuarial rates of moderate-to-severe allograft hepatitis were significantly greater in patients with pT.Bili greater than or equal to 3.5 mg/dl (p=0.004). Multiple regression analysis identified pT.Bili as the only independent predictor of allograft cirrhosis. Conclusions. Features at the onset of histologic HCV recurrence predict the natural history of allograft injury; specifically, marked, transient hyperbilirubinemia is associ ated with the subsequent development of allograft cirrhosis. C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Dept Med, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97207 USA. Univ Washington, Div Virol, Seattle, WA 98195 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Dept Med, 3710 SW US Vet Hosp Rd,POB 1034,111-A, Portland, OR 97207 USA. NR 20 TC 88 Z9 88 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1998 VL 65 IS 9 BP 1178 EP 1182 DI 10.1097/00007890-199805150-00006 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZN734 UT WOS:000073676600006 PM 9603164 ER PT J AU Meehan, SM Pascual, M Williams, WW Tolkoff-Rubin, N Delmonico, FL Cosimi, AB Colvin, RB AF Meehan, SM Pascual, M Williams, WW Tolkoff-Rubin, N Delmonico, FL Cosimi, AB Colvin, RB TI De novo collapsing glomerulopathy in renal allografts SO TRANSPLANTATION LA English DT Article ID FOCAL-SEGMENTAL GLOMERULOSCLEROSIS; NEPHROTIC SYNDROME; LESION; TRANSPLANTS; NEPHROPATHY; CYA AB Background. Collapsing glomerulopathy is a recently described form of glomerular injury characterized by capillary collapse and visceral epithelial hypercellularity associated with nephrotic range proteinuria and a rapid, progressive decline in renal function. The lesion has rarely been described in allografts, Methods. We reviewed 892 allograft biopsies from a population of 1079 recipients who received renal transplants between 1978 and 1996, Results, Five cases of de novo collapsing glomerulopathy were identified (0.6% of biopsies; 3.2% since 1993), None occurred before 1993, The patients were 31 to 66 years of age and they presented 6 to 25 months after transplantation, The 24-hr urinary protein ranged from 1.8 to 11.8 g, All patients and donors were negative for the human immunodeficiency virus and had no risk factors for human immunodeficiency virus infection. Diffuse or focal, global or segmental collapse of glomerular capillaries, swelling and hypercellularity of the visceral epithelium, hyaline arteriolosclerosis, and interstitial fibrosis were characteristic histologic features. Two cases had concomitant glomerular immune complex deposits. Progressive decline in allograft function occurred within 2-24 months after diagnosis, culminating in return to dialysis in all patients. Conclusion. Collapsing glomerulopathy can arise in renal allografts as a de novo disease. Although its pathogenesis remains to be clarified, it is important to distinguish this lesion in allografts as it can be associated with rapidly progressive graft failure. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Meehan, SM (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave,MC6101,Room AMB S-630, Chicago, IL 60637 USA. FU NCI NIH HHS [T32-CA-09216] NR 17 TC 47 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1998 VL 65 IS 9 BP 1192 EP 1197 DI 10.1097/00007890-199805150-00009 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZN734 UT WOS:000073676600009 PM 9603167 ER PT J AU Nikolic, B Lei, H Pearson, DA Sergio, JJ Swenson, KG Sykes, M AF Nikolic, B Lei, H Pearson, DA Sergio, JJ Swenson, KG Sykes, M TI Role of intrathymic rat class II+ cells in maintaining deletional tolerance in xenogeneic rat -> mouse bone marrow chimeras SO TRANSPLANTATION LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; MONOCLONAL-ANTIBODIES; CLONAL DELETION; T-CELLS; NONMYELOABLATIVE REGIMEN; NEGATIVE SELECTION; MIXED CHIMERISM; CLASS-I; MHC; TRANSPLANTATION AB Background, Mixed xenogeneic bone marrow chimerism and tolerance can be induced in mice conditioned with a nonmyeloablative regimen followed by injection of T cell-depleted rat bone marrow cells. We hypothesized that, despite a gradual decline in rat hematopoiesis observed in these chimeras, as long as rat class II+ antigen-presenting cells remain in their thymi, tolerance will persist as a result of deletion of donor-reactive thymocytes. Methods. The level of chimerism and of mouse V beta 5 and V beta 11 T-cell deletion was followed over time. These results were correlated with the presence of rat class II+ cells in the thymus by immunohistochemistry and the presence of tolerance in long-term chimeras by in vivo and in vitro assays. Results. (1) Proliferation and cytotoxicity assays, as well as skin graft survival, demonstrated the presence of specific tolerance to host and to donor rat, with normal reactivity to third-party rat and mouse stimulators, even as late as 85 weeks after bone marrow transplantation, (2) The absence of mature V beta 5(+) and V beta 11(+) host T cells in the thymus and periphery was always associated with the presence of rat class II+ cells in the thymus, and incomplete deletion of T cells expressing these V beta families was observed in thymi in which rat class II+ cells were not detectable. Conclusions. Donor-specific T-cell tolerance is maintained during the period when donor-type reconstitution declines, and is most likely mediated by intrathymic clonal deletion of T cells that recognize antigens expressed on class II+ rat cells. C1 Harvard Univ, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Surg Serv,Sch Med,Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, Surg Serv,Sch Med,Massachusetts Gen Hosp, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R0I HL49915] NR 38 TC 39 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1998 VL 65 IS 9 BP 1216 EP 1224 DI 10.1097/00007890-199805150-00013 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZN734 UT WOS:000073676600013 PM 9603171 ER PT J AU Bagley, J Aboody-Guterman, K Breakefield, X Iacomini, J AF Bagley, J Aboody-Guterman, K Breakefield, X Iacomini, J TI Long-term expression of the gene encoding green fluorescent protein in murine hematopoietic cells using retroviral gene transfer SO TRANSPLANTATION LA English DT Article ID STEM-CELLS; BONE-MARROW; ANTIGEN; TOLERANCE; POPULATIONS; SELECTION; INFECTION; SURVIVAL; THERAPY; EMBRYOS AB Background. A major goal in retroviral-based gene therapy is to establish methods that allow for selection and tracking of transduced cell populations. Green fluorescent protein (GFP) may be useful for gene therapy applications because it is a naturally fluorescent protein that can be detected using conventional flow cytometers facilitating rapid analysis and purification of transduced cell populations. However, it is unknown whether GFP can be stably expressed in vivo, particularly in multiple bone marrow-derived cell lineages, Methods. A murine retrovirus carrying the gene encoding GFP was used to infect murine bone marrow cells (BMCs), These studies were conducted to (1) directly determine whether GFP could be used as a marker of BMC transduction, (2) determine whether GFP is capable of being expressed in multiple bone marrow-derived hematopoietic cell lineages, and (3) determine whether GFP could be used to follow the fate of transduced cells in vivo. Results. Infection of BMCs with retroviruses carrying the gene encoding GFP resulted in a fluorescent signal in viable transduced cells that was detectable by flow cytometry, Expression of GFP was detected in multiple bone marrow-derived cell lineages after transduction, including stem cell antigen-positive (Sca-1(+)), lineage marker-negative (Lin(-)) cells. Using GFP as a selectable marker, we were able to enrich for transduced cells by cell sorting. Mice reconstituted with enriched populations of GFP(+) cells showed a significant increase in the percentage of cells expressing GFP in the periphery when compared with mice reconstituted with unenriched transduced bone marrow. Conclusions. These data indicate that GFP can be used to select for transduced BMCs in vitro, expressed in multiple bone marrow-derived cell lineages, used to select transduced cells, and follow the fate of transduced cells long-term in vivo. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Mol Neurogenet Unit, Serv Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Mol Neurogenet Unit, Serv Neurol, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL48049-05]; NINDS NIH HHS [NS24279] NR 52 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1998 VL 65 IS 9 BP 1233 EP 1240 DI 10.1097/00007890-199805150-00015 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZN734 UT WOS:000073676600015 PM 9603173 ER PT J AU Barzegar, C Meazza, R Pereno, R Pottin-Clemenceau, C Scudeletti, M Brouty-Boye, D Doucet, C Taoufik, Y Ritz, J Musselli, C Mishal, Z Jasmin, C Indiveri, F Ferrini, S Azzarone, B AF Barzegar, C Meazza, R Pereno, R Pottin-Clemenceau, C Scudeletti, M Brouty-Boye, D Doucet, C Taoufik, Y Ritz, J Musselli, C Mishal, Z Jasmin, C Indiveri, F Ferrini, S Azzarone, B TI IL-15 is produced by a subset of human melanomas, and is involved in the regulation of markers of melanoma progression through juxtacrine loops SO ONCOGENE LA English DT Article DE melanomas; IL-15; IL-15R; secretion pattern; tumor progression immunotherapy ID NATURAL-KILLER-CELLS; RECEPTOR-GAMMA CHAIN; INTERLEUKIN-2 RECEPTOR; BETA-CHAIN; FUNCTIONAL INTERLEUKIN-2; GROWTH-FACTOR; ALPHA-CHAIN; EXPRESSION; LINE; IDENTIFICATION AB IL-15 is a novel cytokine active through the IL-2R beta gamma. Since several human melanoma cell lines display functional IL-2Rs, we studied the IL-15/melanoma cells interactions. Ten out of 17 melanoma cell lines express the IL-15 transcript and four of them express levels of IL-15 mRNA similar to those detected in control activated monocytes, Nine out of ten cell lines also express two transcripts for the IL-15R alpha originated by the alternative splicing of exon'3'. Two melanoma cell lines, MELP and MELREO, derived from patients with rapidly progressive primary melanomas, co-express the two IL-15 transcripts, originated by alternative splicing of exon 'A'. Intracellular II-15 protein was only detected in these two cells lines and it is mainly retained in the Endoplasmic Reticulum (ER), However, a small amount of IL-15 is also found in the GoIgi apparatus and in the early endosomes, suggesting production and intercellular trafficking of endogenous IL-15 protein. Nevertheless, no biologically active IL-15 could be detected in the supernatant of all melanoma cells. The anti IL-15 blocking mAb M111 causes the up regulation of;HLA Class I in dense MELP and MELREO cultures, These data suggest that IL-15 is probably active through juxtacrine loops negatively controlling KLA Class I molecules expression. These data offer, for the first time, a likely explanation to the controversal issue of IL-15 secretion and constitute a natural model for understanding IL-15 routing. Moreover, me identify a subset of melanoma cells producing IL-15, possibly involved in tumor escape mechanisms. C1 Hop Paul Brousse, INSERM, U268, F-94807 Villejuif, France. IST, CBA, I-16132 Genoa, Italy. Fac Med, DIMI, I-16132 Genoa, Italy. INSERM, U4, CRI, F-94276 Le Kremlin Bicetre, France. Dana Farber Canc Inst, Boston, MA 02115 USA. CNRS, UPS 47, Lab Cytometrie, F-94800 Villejuif, France. Fac Med, DOCS, I-16132 Genoa, Italy. RP Azzarone, B (reprint author), Hop Paul Brousse, INSERM, U268, F-94807 Villejuif, France. RI Ritz, Jerome/C-7929-2009; OI Ritz, Jerome/0000-0001-5526-4669; Meazza, Raffaella/0000-0003-0242-3157; Ferrini, Silvano/0000-0001-7254-2616 NR 34 TC 39 Z9 40 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 14 PY 1998 VL 16 IS 19 BP 2503 EP 2512 DI 10.1038/sj.onc.1201775 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZN694 UT WOS:000073672300008 PM 9627116 ER PT J AU Halm, EA Fine, MJ Marrie, TJ Coley, CM Kapoor, WN Obrosky, DS Singer, DE AF Halm, EA Fine, MJ Marrie, TJ Coley, CM Kapoor, WN Obrosky, DS Singer, DE TI Time to clinical stability in patients hospitalized with community-acquired pneumonia - Implications for practice guidelines SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 01-03, 1997 CL WASHINGTON, D.C. SP Soc Gen Internal Med ID BACTEREMIC PNEUMOCOCCAL PNEUMONIA; ANTIMICROBIAL THERAPY; LENGTH; STAY; ADULTS; MULTICENTER; MANAGEMENT; SEVERITY; DISEASE; ILLNESS AB Context.-Many groups have developed guidelines to shorten hospital length of stay in pneumonia in order to decrease costs, but the length of time until a patient hospitalized with pneumonia becomes clinically stable has not been established. Objective.-To describe the time to resolution of abnormalities in vital signs, ability to eat, and mental status in patients with community-acquired pneumonia and assess clinical outcomes after achieving stability. Design.-Prospective, multicenter, observational cohort study. Setting.-Three university and 1 community teaching hospital in Boston, Mass, Pittsburgh, Pa, and Halifax, Nova Scotia. Patients.-Six hundred eighty-six adults hospitalized with community-acquired pneumonia. Main Outcome Measures-Time to resolution of vital signs, ability to eat, mental status, hospital length of stay, and admission to an intensive care, coronary care, or telemetry unit. Results.-The median time to stability was 2 days for heart rate (less than or equal to 100 beats/min) and systolic blood pressure (greater than or equal to 90 mm Hg), and 3 days for respiratory rate (less than or equal to 24 breaths/min), oxygen saturation (greater than or equal to 90%), and temperature (less than or equal to 37.2 degrees C [99 degrees F]). The median time to overall clinical stability was 3 days for the most lenient definition of stability and 7 days for the most conservative definition. Patients with more severe cases of pneumonia at presentation took longer to reach stability. Once stability was achieved, clinical deterioration requiring intensive care, coronary care, or telemetry monitoring occurred in 1% of cases or fewer. Between 65% to 86% of patients stayed in the hospital more than 1 day after reaching stability, and fewer than 29% to 46% were converted to oral antibiotics within 1 day of stability, depending on the definition of stability. Conclusions.-Our estimates of time to stability in pneumonia and explicit criteria for defining stability can provide an evidence-based estimate of optimal length of stay, and outline a clinically sensible approach to improving the efficiency of inpatient management. C1 Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Dalhousie Univ, Halifax, NS B3H 3J5, Canada. Victoria Gen Hosp, Dept Med & Microbiol, Halifax, NS B3H 2Y9, Canada. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. RP Halm, EA (reprint author), Mt Sinai Sch Med, Dept Hlth Policy, 1 Gustave L Levy Pl,POB 1077, New York, NY 10029 USA. FU AHRQ HHS [R01 HS06468]; BHP HRSA HHS [PE11001-08] NR 41 TC 276 Z9 282 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 MAY 13 PY 1998 VL 279 IS 18 BP 1452 EP 1457 DI 10.1001/jama.279.18.1452 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZL718 UT WOS:000073463500034 PM 9600479 ER PT J AU Kasturi, R Yuan, J McLean, LR Margolies, MN Ball, WJ AF Kasturi, R Yuan, J McLean, LR Margolies, MN Ball, WJ TI Identification of a model cardiac glycoside receptor: Comparisons with Na(+),K(+)-ATPase SO BIOCHEMISTRY LA English DT Article ID NA,K-ATPASE ALPHA-SUBUNIT; SITE-DIRECTED MUTAGENESIS; CONFERS OUABAIN RESISTANCE; ENERGY-TRANSFER; BETA-SUBUNIT; BINDING; AFFINITY; ATPASE; SENSITIVITY; MUTATION AB The availability of high-affinity anti-digoxin monoclonal antibodies (mAbs) offers the potential for their use as models for the characterization of the relationship between receptor structure and cardiac glycoside binding. We have characterized the binding of anthroylouabain (AO), a fluorescent derivative of the cardiac glycoside ouabain, to mAbs 26-10, 45-20, and 40-50 [Mudgett-Hunter, M., et al. (1995) Mol. Immunol. 22, 477] and lamb kidney Na(+), K(+)-ATPase by monitoring the resultant AO fluorescence emission spectra, anisotropy, lifetime values, and Forster resonance energy transfer (FRET) from protein tryptophan(s) (Trp) to AO. These data suggest that the structural environment in the vicinity of the AO-binding site of Na(+),K(+)-ATPase is similar to that of mAb 26-10 but not mAbs 45-20 and 40-50. A model of AO complexed to the antigen binding fragment (Fab) of mAb 26-10 which was generated using known X-ray crystal structural data [Jeffrey, P. D., et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 10310] shows a heavy chain Trp residue (Trp-H100) that is close (similar to 3 Angstrom) to the anthroyl moiety. This is consistent with the energy transfer seen upon AO binding to mAb 26-10 and suggests that Trp-H100, which is part of the antibody's cardiac glycoside binding site, is a major determinant of the fluorescence properties of bound AO. In contrast, the generated model of AO complexed to Fab 40-50 [Jeffrey, P. D., et al. (1995) J. Mel. Biol. 248, 344] shows a heavy chain Tyr residue (Tyr-H100) which is part of the cardiac glycoside binding site, located similar to 10 Angstrom from the anthroyl moiety. The closest Trp residues (H52 and L35) are located similar to 17 Angstrom from the anthroyl moiety, and no FRET is observed despite the fact that these Trp residues are close enough for significant FRET to occur. The energy transfer seen upon AO binding to Na(+), K(+)-ATPase suggests the presence of one completely quenched or two highly quenched enzyme Trp residues similar to 10 and similar to 17 Angstrom, respectively, from the anthroyl moiety. These data suggest that the Na(+), K(+)-ATPase Trp residue(s) involved in fluorescence energy transfer to AO is likely to be part of the cardiac glycoside binding site. C1 Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. Hoechst Marion Roussel Inc, Cincinnati, OH 45215 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Ball, WJ (reprint author), Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, 231 Bethesda Ave, Cincinnati, OH 45267 USA. EM william.ball@uc.edu FU NHLBI NIH HHS [R01 HL-50613, R01 HL-47415, 5 T32 HL07382] NR 47 TC 7 Z9 7 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 12 PY 1998 VL 37 IS 19 BP 6658 EP 6666 DI 10.1021/bi973037d PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZP874 UT WOS:000073797300005 PM 9578549 ER PT J AU Greenland, P Grundy, S Pasternak, RC Lenfant, C AF Greenland, P Grundy, S Pasternak, RC Lenfant, C TI Problems on the pathway from risk assessment to risk reduction SO CIRCULATION LA English DT Editorial Material DE editorials; risk factors; coronary disease ID AWARENESS C1 Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. Massachusetts Gen Hosp, Cardiac Unit, Dept Med, Div Cardiovasc, Boston, MA 02114 USA. NHLBI, Dept Med, Bethesda, MD 20892 USA. RP Greenland, P (reprint author), Northwestern Univ, Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM p-greenland@nwu.edu NR 13 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 12 PY 1998 VL 97 IS 18 BP 1761 EP 1762 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZM245 UT WOS:000073519200002 PM 9603527 ER PT J AU O'Donnell, CJ Lindpaintner, K Larson, MG Rao, VS Ordovas, JM Schaefer, EJ Myers, RH Levy, D AF O'Donnell, CJ Lindpaintner, K Larson, MG Rao, VS Ordovas, JM Schaefer, EJ Myers, RH Levy, D TI Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study SO CIRCULATION LA English DT Article DE angiotensin; trials; genetics; genes; hormones; hypertension; blood pressure ID CORONARY-ARTERY DISEASE; DELETION POLYMORPHISM; MYOCARDIAL-INFARCTION; INCREASED RISK; POPULATION; FAMILIES; DNA; SEGREGATION; FERTILITY; JAPANESE AB Background-There is controversy regarding the association of the angiotensin-converting enzyme deletion-insertion (ACE D/I) polymorphism with systemic hypertension and with blood pressure. We investigated these relations in a large population-based sample of men and women by using association and linkage analyses. Methods and Results-The study sample consisted of 3095 participants in the Framingham Heart Study. Blood pressure measurements were obtained at regular examinations. The ACE D/I polymorphism was identified by using a polymerase chain reaction assay. In logistic regression analysis, the adjusted odds ratios for hypertension among men for the DD and DI genotypes were 1.59 (95% confidence interval [CI], 1.13 to 2.23) and 1.18 (95% CI, 0.87 to 1.62), respectively, versus II (Chi(2) P=.02). In women, adjusted odds ratios for the DD and DI genotypes were 1.00 (95% CI, 0.70 to 1.44) and 0.78 (95% CI, 0.56 to 1.09), respectively (P=.14). In linear regression analysis, there was an association of the ACE DD genotype with increased diastolic blood pressure in men (age-adjusted P=.03, multivariate-adjusted P=.14) but not women. Quantitative trait linkage analyses in 1044 pairs of siblings, by using both ACE D/I and a nearby microsatellite polymorphism of the human growth hormone gene, supported a role of the ACE locus in influencing blood pressure in men but not in women. Conclusions-In our large, population-based sample, then is evidence for association and genetic linkage of the ACE locus with hypertension and with diastolic blood pressure in men but not women, Our data support the hypothesis that ACE, or a nearby gene, is a sex-specific candidate gene for hypertension. Confirmatory studies in other large population-based samples are warranted. C1 NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit,Dept Med, Boston, MA USA. Harvard Univ, Beth Israel Hosp, Sch Med, Div Cardiol, Boston, MA USA. Harvard Univ, Beth Israel Hosp, Sch Med, Div Clin Epidemiol, Boston, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Cardiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA USA. Tufts Univ, Mol Biol Sect, Lipid Metab Lab, Jean Mayer US Dept Agr,Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01701 USA. EM chris@fram.nhlbi.nih.gov FU NHLBI NIH HHS [HL-54776, K04-HL-03138-01, N01-HC-38038] NR 45 TC 380 Z9 398 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 12 PY 1998 VL 97 IS 18 BP 1766 EP 1772 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZM245 UT WOS:000073519200004 PM 9603529 ER PT J AU Yeghiayan, SK Gongwer, MA Baldessarini, RJ Kula, NS Zong, R Neumeyer, JL AF Yeghiayan, SK Gongwer, MA Baldessarini, RJ Kula, NS Zong, R Neumeyer, JL TI Local injection of alkylating and nonalkylating dopamine receptor antagonists into rat basal forebrain: autoradiographic assessment of D-2-like and D-3 sites SO BRAIN RESEARCH LA English DT Article DE alkylating agent; D-2-like receptor; D-3 receptor; dopamine; EEDQ; 7-OH-DPAT; fluphenazine; autoradiography; accumbens; Islands of Calleja ID 7-OH-DPAT; BINDING; BRAIN AB N-chloroethyl derivatives of 7-hydroxy-1,2,3,4-tetrahydronaphthalene (7-OH-DPAT), 1-ethoxycarbonyl-2-ethoxy-1,7-dihydroquinoline (EEDQ), or fluphenazine were microinjected into rat nucleus accumbens (Acc), and receptor binding quantified autoradiographically after 24 h. EEDQ reduced [H-3]nemonapride (D-2-like receptors) binding in Acc (by 84%) and islands of Calleja (IC; 44%), without affecting [H-3](+)-7-OH-DPAT (D-3); N-chloroethyl-7-OH-DPATs blocked both radioligands in Acc and IC (30%-70%); fluphenazine had no effect. (C) 1998 Elsevier Science B.V. C1 Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02178 USA. RP Yeghiayan, SK (reprint author), USA, Nutr & Biochem Div, Environm Med Res Inst, Kansas St, Natick, MA 01760 USA. EM syeghiayan@natick-ccmail.army.mil FU NIMH NIH HHS [MH-47370, MH-14275, MH-34006] NR 14 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 11 PY 1998 VL 792 IS 2 BP 324 EP 326 DI 10.1016/S0006-8993(98)00202-9 PG 3 WC Neurosciences SC Neurosciences & Neurology GA ZU326 UT WOS:000074185500017 PM 9593972 ER PT J AU Balasubramanyam, A Iyer, D Stringer, JL Beaulieu, C Potvin, A Neumeyer, AM Avruch, J Epstein, HF AF Balasubramanyam, A Iyer, D Stringer, JL Beaulieu, C Potvin, A Neumeyer, AM Avruch, J Epstein, HF TI Developmental changes in expression of myotonic dystrophy protein kinase in the rat central nervous system SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE hippocampus; cerebral cortex; spinal cord; entorhinal cortex; memory ID MUSCULAR-DYSTROPHY; COGNITIVE FUNCTION; SKELETAL-MUSCLE; CTG REPEAT; GENE; INVOLVEMENT; PATTERNS; DISEASE; BINDING; REGION AB Myotonic dystrophy protein kinase (DMPK) is the protein product of the genetic locus associated with myotonic dystrophy, in which alterations of muscle excitability, cardiac conduction defects, mental retardation, and cognitive deficiencies are inherited as an autosomal dominant trait. DMPK belongs to a novel protein serine/threonine kinase family, but its regulation and physiological functions have not been specified. In a first step toward understanding the functions of DMPK in the central nervous system, we have characterized its localization and developmental pattern of expression in rat brain and spinal cord by using a monospecific rabbit antiserum produced against bacterially expressed DMPK. Expression of DMPK begins after birth and increases gradually to peak at postnatal day 21 with antibody labeling of neuronal cell types in many regions. After postnatal day 21 and proceeding to the adult, the pattern of expression becomes more restricted, with localization to certain regions or cell groups in the central nervous system. Electron microscopy reveals localization within adult spinal motor neurons to the endoplasmic reticulum and dendritic microtubules. The adult localizations suggest that DMPK may function in membrane trafficking and secretion within neurons associated with cognition, memory, and motor control. (C) 1998 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Med, Div Endocrinol, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. Univ Montreal, Dept Pathol, Montreal, PQ H3T 1J4, Canada. Massachusetts Gen Hosp, Day Neuromuscular Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Diabet Unit, Charlestown, MA 02129 USA. RP Balasubramanyam, A (reprint author), Baylor Coll Med, Dept Med, Div Endocrinol, Room 549 E,1 Baylor Plaza, Houston, TX 77030 USA. EM ashokb@bcm.tmc.edu FU NEI NIH HHS [EY09708]; NIDDK NIH HHS [K12 DK01410]; NINDS NIH HHS [NS01784] NR 41 TC 6 Z9 6 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 11 PY 1998 VL 394 IS 3 BP 309 EP 325 DI 10.1002/(SICI)1096-9861(19980511)394:3<309::AID-CNE3>3.0.CO;2-5 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA ZJ218 UT WOS:000073191300003 PM 9579395 ER PT J AU Kawamata, T Ren, JM Chan, TCK Charette, M Finklestein, SP AF Kawamata, T Ren, JM Chan, TCK Charette, M Finklestein, SP TI Intracisternal osteogenic protein-1 enhances functional recovery following focal stroke SO NEUROREPORT LA English DT Article DE behavior; bone morphogenetic proteins; cerebral ischemia; focal cerebral infarction; osteogenic protein-1; recovery; stroke ID CEREBRAL-ARTERY OCCLUSION; NEOCORTICAL DAMAGE; RATS; CONSEQUENCES; SENSORIMOTOR; INFARCTION; EXPRESSION; NEURONS; GROWTH; BRAIN AB OSTEOGENIC protein-1 (OP-1, BMP-7) is a member of the transforming growth factor-beta (TGF-beta) superfamily that selectively induces dendritic outgrowth from cultured neurons. We injected human recombinant OP-1 (1 or 10 mu g) or vehicle into the cisterna magna of mature male Sprague-Dawley rats 1 and 4 days after focal cerebral infarction induced by middle cerebral artery (MCA) occlusion. OP-1 treatment was associated with a marked enhancement of recovery of sensorimotor function of the impaired forelimb and hindlimb (contralateral to infarcts) as assessed by limb placing tests. This effect appeared to be dose dependent. There was no difference in infarct volume between OP-1 and vehicle-treated rats. The mechanisms of enhanced recovery by intracisternal OP-1 may include promotion of dendritic sprouting in the intact uninjured brain. (C) 1998 Rapid Science Ltd. C1 Massachusetts Gen Hosp, Dept Neurol, CNS Growth Factor Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Creat BioMol Inc, Hopkinton, MA USA. RP Finklestein, SP (reprint author), Massachusetts Gen Hosp, Dept Neurol, CNS Growth Factor Res Lab, Warren 408, Boston, MA 02114 USA. FU PHS HHS [P01-10828] NR 23 TC 73 Z9 75 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 11 PY 1998 VL 9 IS 7 BP 1441 EP 1445 DI 10.1097/00001756-199805110-00035 PG 5 WC Neurosciences SC Neurosciences & Neurology GA ZR650 UT WOS:000074000000037 PM 9631444 ER PT J AU Rojas, DC Walker, JR Sheeder, JL Teale, PD Reite, ML AF Rojas, DC Walker, JR Sheeder, JL Teale, PD Reite, ML TI Developmental changes in refractoriness of the neuromagnetic M100 in children SO NEUROREPORT LA English DT Article DE auditory evoked fields; children; development; magnetoencephalography (MEG); neuromagnetism; N100m ID EVOKED MAGNETIC-FIELDS; PRESCHOOL-CHILDREN; POTENTIALS; CORTEX; MEMORY; COMPONENT; SPEECH AB CONSIDERABLE evidence exists for developmental changes in latency and amplitude of the auditory evoked potential termed N100. However, it is widely recognized that the N100 wave comprises multiple, temporally overlapping neural generators, and few data are available addressing either individual generator development or mechanisms behind such change. Using magnetoencelphalographic (MEG) measurements of the magnetic analog of the N100 termed the M100, which derives primarily from supra-temporal auditory generators, it is demonstrated here that changes in the response of that waveform to manipulation of interstimulus interval (ISI) occur between the ages of 6 and 18 years of age. (C) 1998 Rapid Science Ltd. C1 Univ Colorado, Hlth Sci Ctr, Neuromagnetism Lab, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Rojas, DC (reprint author), Univ Colorado, Hlth Sci Ctr, Neuromagnetism Lab, Box C268-68,4200 E 9th Ave, Denver, CO 80262 USA. RI Rojas, Don/F-4296-2012; OI Rojas, Don/0000-0001-6560-9616; Sheeder, Jeanelle/0000-0002-4463-3569 FU NIMH NIH HHS [MH15442, MH47476, MH56601] NR 25 TC 42 Z9 42 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 11 PY 1998 VL 9 IS 7 BP 1543 EP 1547 PG 5 WC Neurosciences SC Neurosciences & Neurology GA ZR650 UT WOS:000074000000057 PM 9631464 ER PT J AU Zhang, JL Choe, H Dezube, BJ Farzan, M Sharma, PL Zhou, XC Chen, LB Ono, M Gillies, S Wu, YM Sodroski, JG Crumpacker, CS AF Zhang, JL Choe, H Dezube, BJ Farzan, M Sharma, PL Zhou, XC Chen, LB Ono, M Gillies, S Wu, YM Sodroski, JG Crumpacker, CS TI The bis-azo compound FP-21399 inhibits HIV-1 replication by preventing viral entry SO VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HTLV-III/LAV ENVELOPE; T-CELL-LINE; SOLUBLE CD4; SYNCYTIUM FORMATION; MEMBRANE-FUSION; GLYCOPROTEIN GP120; MACROPHAGE TROPISM; FUNCTIONAL-ROLE; V1/V2 REGION AB The bis-azo compound FP-21399 inhibits HIV-1 infection. We now show that FP-21399 acts on the HIV-1 envelope glycoprotein to prevent viral replication. This compound targets the entry step of the HIV-1 replication cycle as demonstrated by time-of-addition and single cycle viral entry assays. The entry of SIV(mac)239, which uses the same coreceptors (CD4/CCR5) as HIV-1, was not inhibited by FP-21399, indicating that the antiviral effect of FP-21399 is specific for the HIV-1 envelope glycoprotein and is not dependent upon the cellular receptors CD4 and CCR5. FP-21399 inhibits neither the activity of HIV-1 reverse transcriptase nor the expression of HIV-1 early mRNA. Finally, this compound inhibits gp120 shedding of the T-tropic virus. Our results suggest that the anti-HIV activity of FP-21399 is due to its interaction with HIV-1 gp120/41 complex during viral entry. (C) 1998 Academic Press. C1 Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Fuji ImmunoPharmaceut Corp, Lexington, MA 02173 USA. RP Crumpacker, CS (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Charles A Dana Res Bldg,Dana 617,330 Brookline Av, Boston, MA 02215 USA. EM ccrumpac@bidmc.harvard.edu FU NIAID NIH HHS [AI28691]; PHS HHS [2271] NR 46 TC 22 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 10 PY 1998 VL 244 IS 2 BP 530 EP 541 DI 10.1006/viro.1998.9115 PG 12 WC Virology SC Virology GA ZP778 UT WOS:000073787500027 PM 9601521 ER PT J AU Inoue, G Cheatham, B Emkey, R Kahn, CR AF Inoue, G Cheatham, B Emkey, R Kahn, CR TI Dynamics of insulin signaling in 3T3-L1 adipocytes - Differential compartmentalization and trafficking of insulin receptor substrate (IRS)-1 and IRS-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; GROWTH-FACTOR; HEXOSE-TRANSPORT; DOCKING PROTEIN; MEMBRANE; KINASE; PHOSPHORYLATION; STIMULATION; CELLS AB The ability of the insulin receptor to phosphorylate multiple substrates and their subcellular localization are two of the determinants that contribute to diversity of signaling, We find that insulin receptor substrate (IRS)-1 is 2-fold more concentrated in the intracellular membrane (IM) compartment than in cytosol, whereas IRS-2 is 2-fold more concentrated in cytosol than in IM. Insulin stimulation induces rapid tyrosine phosphorylation of both IRS-1 and IRS-2. This occurs mainly in the IM compartment, even though IRS-S is located predominantly in cytosol, Furthermore, after insulin stimulation, both IRS-1 and IRS-2 translocate from IRI to cytosol with a t(1/2) of 3.5 min. Using an in vitro reconstitution assay, we have demonstrated an association between IRS-1 and internal membranes and have shown that the dissociation of IRS-1 from IM is dependent on serine/ threonine phosphorylation of IM. By comparison, within 1 min after insulin stimulation, 40% of the total pool of the 85-kDa subunit of phosphatidylinositol 3-kinase (p85) is recruited from cytosol to IM, the greater part of which can be accounted for by binding to IRS-1 present in the IM. The p85 binding and phosphatidylinositol 3-kinase activity associated with IRS-2 rapidly decrease in both IM and cytosol, whereas those associated with IRS-1 stay at a relatively high level in IM and increase with time in cytosol despite a return of p85 to the cytosol and decreasing tyrosine phosphorylation of cytosolic IRS-1. These data indicate that IRS-1 and IRS-2 are differentially distributed in the cell and move from IRI to cytosol following insulin stimulation. Insulin-stimulated IRS-1 and IRS-S signaling occurs mainly in the IM and shows different kinetics; IRS-l-mediated signaling is more stable, whereas IRS-a-mediated signaling is more transient. These differences in substrate utilization and compartmentalization may contribute to the complexity and diversity of the insulin signaling network. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, Rm 620,1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 31036, DK 36836] NR 36 TC 139 Z9 141 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 1998 VL 273 IS 19 BP 11548 EP 11555 DI 10.1074/jbc.273.19.11548 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZM408 UT WOS:000073536700024 PM 9565570 ER PT J AU Chen, Y Le Caherec, F Chuck, SL AF Chen, Y Le Caherec, F Chuck, SL TI Calnexin and other factors that alter translocation affect the rapid binding of ubiquitin to ApoB in the Sec61 complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEP G2 CELLS; ENDOPLASMIC-RETICULUM MEMBRANE; APOLIPOPROTEIN-B; INTRACELLULAR DEGRADATION; PROTEASOME PATHWAY; SECRETORY PROTEIN; LIPOPROTEINS; BIOSYNTHESIS; PROTEOLYSIS; HEPATOCYTES AB Several secretory proteins, including apolipoprotein B, have been shown to undergo degradation by proteasomes. We found that the rapid degradation of nascent apolipoprotein B in HepG2 cells was diminished but not abolished by the addition of any of three different inhibitors of proteasomes, Ubiquitin is conjugated to apolipoprotein B that is not assembled with sufficient lipids either during or soon after synthesis, In addition, we found that apolipoprotein B that has entered the endoplasmic reticulum sufficiently to become glycosylated can be degraded by proteasomes. Furthermore, we detected ubiquitin-apolipoprotein B that is associated with the Sec61 complex, the major constituent of the translocational channel. Treatment of cells with monomethylethanolamine or dithiothreitol decreased the translocation of apolipoprotein B and increased the proportion of ubiquitin-conjugated molecules associated with Sec61. Conversely, treatment of cells with oleic acid, which increased the proportion of translocated apolipoprotein B, decreased the amount of ubiquitin-apolipoprotein B in the Sec61 complex. Finally, we found that inhibition of the interaction between calnexin and apolipoprotein B decreases the translocation of apolipoprotein B, increases the ubiquitin-apolipoprotein B in the Sec61 complex, and increases the proteasomal degradation of glycosylated apolipoprotein B, Thus, ubiquitin can be attached to unassembled apolipoprotein B in the Sec61 complex, and this process is affected by factors including calnexin that alter the translocation of apolipoprotein B. C1 Beth Israel Deaconess Med Ctr E, Dept Med, Mol Med Unit, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Chuck, SL (reprint author), Beth Israel Deaconess Med Ctr E, Dept Med, Mol Med Unit, RW 663,330 Brookline Ave, Boston, MA 02215 USA. NR 50 TC 78 Z9 78 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 8 PY 1998 VL 273 IS 19 BP 11887 EP 11894 DI 10.1074/jbc.273.19.11887 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZM408 UT WOS:000073536700069 PM 9565615 ER PT J AU Irving, BA Alt, FW Killeen, N AF Irving, BA Alt, FW Killeen, N TI Thymocyte development in the absence of pre-T cell receptor extracellular immunoglobulin domains SO SCIENCE LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAYS; ANTIGEN RECEPTOR; MUTANT MICE; ALPHA-BETA; DEFICIENT MICE; CHAIN; EXPRESSION; GENE; LCK; DIFFERENTIATION AB Immature thymocytes express a pre-T cell receptor (pre-TCR) composed of the TCR beta chain paired with pre-T alpha. Signals from this receptor are essential for passage of thymocytes through a key developmental checkpoint in the thymus. These signals were efficiently delivered in vivo by a truncated form of the murine pre-TCR that lacked all of its extracellular immunoglobulin domains. De novo expression of the truncated pre-TCR or an intact alpha beta TCR was sufficient to activate characteristic TCR signaling pathways in a T cell line. These findings support the view that recognition of an extracellular ligand is not required for pre-TCR function. C1 Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Genet & Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Killeen, N (reprint author), Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. NR 43 TC 139 Z9 139 U1 0 U2 0 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 MAY 8 PY 1998 VL 280 IS 5365 BP 905 EP 908 DI 10.1126/science.280.5365.905 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZM380 UT WOS:000073532900042 PM 9572735 ER PT J AU Holsinger, LJ Graef, IA Swat, W Chi, T Bautista, DM Davidson, L Lewis, RS Alt, FW Crabtree, GR AF Holsinger, LJ Graef, IA Swat, W Chi, T Bautista, DM Davidson, L Lewis, RS Alt, FW Crabtree, GR TI Defects in actin-cap formation in Vav-deficient mice implicate an actin requirement for lymphocyte signal transduction SO CURRENT BIOLOGY LA English DT Article ID T-CELL ACTIVATION; ALDRICH SYNDROME PROTEIN; ANTIGEN RECEPTOR; CYCLOSPORINE-A; STRESS FIBERS; GTPASE CDC42; RAC; RHO; PATHWAY; POLYMERIZATION AB Background: Antigen-receptor interactions on lymphocytes result in local clustering of actin, receptors and signaling molecules into an asymmetric membrane structure termed a cap. Although actin polymerization is known to be required, the mechanisms underlying cap formation are unclear. We have studied the events underlying cap formation using mice bearing a null mutation in vav (vav(-/-)), a gene that encodes a guanine-nucleotide exchange factor for the GTPase Pac. Results: Lymphocytes from vav(-/-) mice failed to form T-cell receptor caps following activation and had a defective actin cytoskeleton. The vav(-/-) cells were deficient in interleukin-2 (IL-2) production and proliferation, and the peak of Ca2+ mobilization was reduced although of normal duration. Activation of Jun N-terminal kinase or stress-activated kinase (JNK or SAPK) and mitogen-activated protein kinase (MAPK) and the induction of the transcription factor NF-ATc1 and egr-1 genes was normal. Despite the reduced Ca2+ mobilization, translocation of cytoplasmic NF-ATc to the nucleus was normal, reflecting that the lower levels of Ca2+ in vav(-/-) cells were still sufficient to activate calcineurin. Treatment of lymphocytes with cytochalasin D, which blocks actin polymerization, inhibited cap formation and produced defects in signaling and IL-2 transcriptional induction in response to antigen-receptor signaling that were nearly identical to those seen in vav(-/-) cells. In transfection studies, either constitutively active Vav or Rac could complement constitutively active calcineurin to activate NF-AT-dependent transcription. Conclusions: These results indicate that Vav is required for cap formation in lymphocytes, Furthermore, the correlation between cap formation, IL-2 production and proliferation supports the hypothesis that an actin-dependent pathway is a source of specialized growth regulatory signals. (C) Current Biology Ltd ISSN 0960-9822. C1 Stanford Univ, Sch Med, Howard Hughes Med Inst, Beckman Ctr Mol & Genet Med,Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Beckman Ctr Mol & Genet Med,Dept Dev Biol, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Dept Genet, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Cellular & Mol Physiol, Stanford, CA 94305 USA. RP Crabtree, GR (reprint author), Stanford Univ, Sch Med, Howard Hughes Med Inst, Beckman Ctr Mol & Genet Med,Dept Pathol, Stanford, CA 94305 USA. NR 51 TC 345 Z9 348 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 7 PY 1998 VL 8 IS 10 BP 563 EP 572 DI 10.1016/S0960-9822(98)70225-8 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZM927 UT WOS:000073590300014 PM 9601640 ER PT J AU Dahia, PLM FitzGerald, MG Zhang, X Marsh, DJ Zheng, ZM Pietsch, T von Deimling, A Haluska, FG Haber, DA Eng, C AF Dahia, PLM FitzGerald, MG Zhang, X Marsh, DJ Zheng, ZM Pietsch, T von Deimling, A Haluska, FG Haber, DA Eng, C TI A highly conserved processed PTEN pseudogene is located on chromosome band 9p21 SO ONCOGENE LA English DT Article DE MMAC1; TEP1; 9p; Cowden; pseudogene ID COWDEN DISEASE; DELETIONS; GENE AB PTEN/MMAC1/TEP1, encoding a dual-specificity phosphatase, is a tumor suppressor gene which has recently been cloned and mapped to chromosome 10q23.3. We have shown that germline mutations of PTEN are present in individuals with two hamartoma syndromes: Cowden Syndrome, associated with a predisposition to breast and thyroid cancers, and Bannayan-Zonana syndrome. Somatic mutations of PTEN have been reported in a variety of human cancer cell lines, suggesting a potential role for this gene in the pathogenesis of human malignancies. We report the identification of a highly conserved PTEN processed pseudogene, psi PTEN, which shares over 98% homology with the coding region of functional PTEN, and its localisation to chromosome 9p21. The high sequence homology of psi PTEN with the PTEN transcript may potentially lead to misinterpretation when performing mutation analyses based on cDNA templates. Caution should be exerted when using such screening approaches. C1 Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Dept Adult Oncol, Translat Res Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Program Populat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Univ Bonn, Med Ctr, Dept Neuropathol, D-53105 Bonn, Germany. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. RP Eng, C (reprint author), Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Dept Adult Oncol, Translat Res Lab, SM822, Boston, MA 02115 USA. RI Marsh, Deborah/I-1491-2014; von Deimling, Andreas/F-7774-2013; OI Marsh, Deborah/0000-0001-5899-4931; von Deimling, Andreas/0000-0002-5863-540X; Eng, Charis/0000-0002-3693-5145 NR 18 TC 60 Z9 62 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 7 PY 1998 VL 16 IS 18 BP 2403 EP 2406 DI 10.1038/sj.onc.1201762 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZL389 UT WOS:000073428000013 PM 9620558 ER PT J AU Qian, F Leung, A Abou-Samra, A AF Qian, F Leung, A Abou-Samra, A TI Agonist-dependent phosphorylation of the parathyroid hormone parathyroid hormone-related peptide receptor SO BIOCHEMISTRY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; OSTEO-SARCOMA CELLS; PROTEIN-KINASE-C; PTH-RELATED PEPTIDE; ROS 17/2.8 CELLS; DOWN-REGULATION; EXPRESSION CLONING; ADENYLATE-CYCLASE; BETA-ARRESTIN; KIDNEY-CELLS AB Native PTH/PTHrP receptors in ROS 17/2.8 cells are downregulated after PTH treatment. Since downregulation may involve receptor phosphorylation, we examined PTH/PTHrP receptor phosphorylation in ROS 17/2.8 cells and we mapped the agonist-induced phosphorylation sites using recombinant PTH/PTHrP receptors expressed in LLCPK-1 and COS-7 cells. The data show that the PTH/PTHrP receptor is rapidly phosphorylated in ROS 17/2.8 cells with a maximum occurring at 20 min. The phosphorylation was dose-dependent; it occurred with PTH concentrations that are known to downregulate the PTH/PTHrP receptor in ROS 17/2.8 cells. The time course and the dose requirement for phosphorylation were similar in ROS 17/2.8 cells, which express native PTH/PTHrP receptors, and in LLCPK-1 cells stably transfected with the PTH/PTHrP receptor cDNA. PTH/PTHrP receptor phosphorylation in ROS 17/2.8, COS-7, and LLCPK-1 cells was also stimulated with forskolin and phorbol myristate acetate (PMA). Additionally, in LLCPK-1 cells, which express native clacitonin receptors, PTH/PTHrP receptor phosphorylation was stimulated by calcitonin. These data suggest involvement of second messenger-stimulated kinases in PTH/PTHrP receptor phosphorylation. However, staurosporine, which fully blocked the effects of PMA, forskolin, and clacitonin, partially decreased the effects of PTH on PTH/PTHrP receptor phosphorylation. These data indicate involvement of other kinase(s) in PTH-induced PTH/PTHrP receptor phosphorylation. CNBr cleavage of recombinant receptors expressed in COS-7 cells combined with site-directed mutagenesis revealed that the phosphorylated residues of the PTH/PTHrP receptor map to two regions of the carboxyl-terminal tail located between residues A480 and M499 and residues M499 and M553. These data indicate that the PTH/PTHrP receptor is phosphorylated after PTH stimulation on two regions of the carboxyl-terminal tail and that agonist-dependent phosphorylation involves both staurosporine-sensitive and -insensitive kinases. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Abou-Samra, A (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM Samra@helix.mgh.harvard.edu RI Leung, Albert/H-6030-2013; OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK11794-26] NR 34 TC 25 Z9 25 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 5 PY 1998 VL 37 IS 18 BP 6240 EP 6246 DI 10.1021/bi9726281 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZM880 UT WOS:000073585600004 PM 9572838 ER PT J AU Williams, SB Goldfine, AB Timimi, FK Ting, HH Roddy, MA Simonson, DC Creager, MA AF Williams, SB Goldfine, AB Timimi, FK Ting, HH Roddy, MA Simonson, DC Creager, MA TI Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo SO CIRCULATION LA English DT Article DE diabetes mellitus; endothelium-derived factors; vasodilation; glucose; nitric oxide ID PROTEIN-KINASE-C; DIABETIC RAT AORTA; VASCULAR SMOOTH-MUSCLE; NITRIC-OXIDE SYNTHESIS; ELEVATED GLUCOSE; FREE-RADICALS; SUPEROXIDE ANION; RELAXING FACTOR; HUMAN FOREARM; AUTOXIDATIVE GLYCOSYLATION AB Background-Endothelial function is impaired in patients with diabetes mellitus, However, the factors contributing to this defect are currently unknown. Hyperglycemia attenuates endothelium-dependent relaxation in normal rabbit arteries in vitro and rat arterioles in vivo. Accordingly, this study examined the effect of acute hyperglycemia on endothelium-dependent vasodilation in nondiabetic humans in vivo. Methods and Results-Endothelium-dependent vasodilation was assessed through brachial artery infusion of methacholine chloride both before and during 6 hours of local hyperglycemia (300 mg/dL) achieved by intra-arterial infusion of 50% dextrose, Forearm blood flow was determined by plethysmography, In a group of 10 subjects, there was a trend toward attenuated methacholine-mediated vasodilation during hyperglycemia compared with euglycemia (P=.07 by ANOVA; maximal response, 13.3+/-2.8 versus 14.7+/-1.5 mL . min(-1). 100 mL(-1), respectively). In these subjects, the systemic serum insulin levels increased significantly during the dextrose infusion (P<.001), To eliminate the confounding vasoactive effects of insulin, the protocol was repeated during systemic infusion of octreotide (30 ng . kg(-1). min(-1)) to inhibit pancreatic secretion of insulin. In these subjects (n=10), hyperglycemia significantly attenuated the forearm blood flow response to methacholine (P<.01 by ANOVA; maximal response, 16.9+/-2.5 before versus 12.7+/-1.8 mL . min(-1). 100 mL(-1) during hyperglycemia). Methacholine-mediated vasodilation was not attenuated by an equimolar infusion of mannitol (P>.40), nor did hyperglycemia reduce endothelium-independent vasodilation to verapamil (P>.50), Conclusions-Acute hyperglycemia impairs endothelium-dependent vasodilation in healthy humans in vivo. This finding suggests that elevated glucose may contribute to the endothelial dysfunction observed in patients with diabetes mellitus. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Vasc Med & Atherosclerosis Unit, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrine, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Creager, MA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Cardiovasc Div,Vasc Med & Atherosclerosis Unit, 75 Francis St, Boston, MA 02115 USA. FU NCRR NIH HHS [M01-RR-02635]; NHLBI NIH HHS [HL-02663, HL-48743] NR 55 TC 486 Z9 508 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 5 PY 1998 VL 97 IS 17 BP 1695 EP 1701 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZL983 UT WOS:000073493100006 PM 9591763 ER PT J AU Gerszten, RE Lim, YC Ding, HT Snapp, K Kansas, G Dichek, DA Cabanas, C Sanchez-Madrid, F Gimbrone, MA Rosenzweig, A Luscinskas, FW AF Gerszten, RE Lim, YC Ding, HT Snapp, K Kansas, G Dichek, DA Cabanas, C Sanchez-Madrid, F Gimbrone, MA Rosenzweig, A Luscinskas, FW TI Adhesion of monocytes to vascular cell adhesion molecule-1-transduced human endothelial cells - Implications for atherogenesis SO CIRCULATION RESEARCH LA English DT Article DE adenovirus; adhesion; atherosclerosis; mononuclear leukocyte ID PHYSIOLOGICAL FLOW CONDITIONS; L-SELECTIN; HUMAN ATHEROSCLEROSIS; ROLLING ADHESIONS; VCAM-1; LYMPHOCYTES; EXPRESSION; MOLECULE-1; ARREST; IDENTIFICATION AB To study the role of vascular cell adhesion molecule-1 (VCAM-1) in monocyte recruitment and atherogenesis, we constructed a recombinant adenovirus, AdRSVrVCAM-1, carrying the rabbit VCAM-1 cDNA. We have previously shown that AdRSVrVCAM-1-transduced human umbilical vein endothelial cells (HUVECs) support the adhesion of CD4(+) CD45RO(+) memory T lymphocytes under laminar flow conditions. We now demonstrate that AdRSVrVCAM-1-transduced HUVECs support the adhesion of peripheral blood monocytes at a sheer stress of less than or equal to 1.5 dyne/cm(2). Although VCAM-1 supported only firm adhesion of lymphocytes, it was able to mediate monocyte rolling, firm adhesion, and transmigration when expressed in the context of otherwise unactivated vascular endothelium. VCAM-1-transduced HUVECs supported the adhesion of as many as 4-fold more monocytes than T cells under laminar flow. The greater monocyte adhesion was explained at least in part by leukocyte-leukocyte interactions (secondary adhesions), which were not seen with T cells. These secondary monocyte interactions were specifically blocked by monoclonal antibodies to L-selectin and P-selectin glycoprotein ligand-1. These data demonstrate that VCAM-1 expressed in the context of unactivated vascular endothelium supports the adhesion of the leukocyte populations present in atherosclerotic plaque and may contribute to the predominance of monocytes over lymphocytes. C1 Brigham & Womens Hosp, Div Vasc Res, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. Univ Complutense Madrid, Madrid, Spain. Hosp Princesa, Serv Inmunol, Madrid, Spain. Northwestern Univ, Sch Med, Dept Microbiol Immunol, Chicago, IL 60611 USA. RP Luscinskas, FW (reprint author), Brigham & Womens Hosp, Div Vasc Res, Dept Pathol, 221 Longwood Ave, Boston, MA 02115 USA. EM fluscinska@rics.bwh.harvard.edu RI Sanchez-Madrid, Francisco/M-7889-2016; CABANAS, CARLOS/J-4595-2012 OI Sanchez-Madrid, Francisco/0000-0001-5303-0762; CABANAS, CARLOS/0000-0002-8767-060X FU NHLBI NIH HHS [HL-54202, HL-03348]; NIAID NIH HHS [AI-40970] NR 27 TC 80 Z9 81 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY 4 PY 1998 VL 82 IS 8 BP 871 EP 878 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA ZM238 UT WOS:000073518500005 PM 9580553 ER PT J AU Ghendler, Y Smolyar, A Chang, HC Reinherz, EL AF Ghendler, Y Smolyar, A Chang, HC Reinherz, EL TI One of the CD3 epsilon subunits within a T cell receptor complex lies in close proximity to the C beta FG loop SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODY; TCR/CD3 COMPLEX; SURFACE EXPRESSION; TCR-BETA; ALLOTYPIC DETERMINANT; T3-MOLECULAR COMPLEX; ACTIVATION MOTIFS; CROSS-LINKING; MICE LACKING AB A recent crystal structure of the N15 alpha/beta-T cell receptor (TCR) in complex with an Fab derived from the H57 C beta-specific monoclonal antibody (mAb) shows the mAb fragment inter acting with the elongated FG loop of the C beta domain. This loop creates one side wall of a cavity within the TCR Ti-alpha/beta constant region module (C alpha C beta) while the CD and EF loops of the C alpha domain form another wall. The cavity size is sufficient to accommodate a single nonglycosylated Ig domain such as the CD3 epsilon ectodomain. By using specific mAbs to mouse TCR-beta (H57) and CD3 epsilon (2C11) subunits, we herein provide evidence that only one of the two CD3 epsilon chains within the TCR complex is located in close proximity to the TCR C beta FG loop, in support of the above notion. Moreover, analysis of T cells isolated from transgenic mice expressing both human and mouse CD3 epsilon genes shows that the heterologous human CD3 epsilon component can replace the mouse CD3 epsilon at this site. The location of one CD3 epsilon subunit within the rigid constant domain module has implications for the mechanism of signal transduction throughout T cell development. C1 Childrens Hosp, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Childrens Hosp, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [R56 AI019807, R01 AI019807, AI-19807, AI-39098, R37 AI019807] NR 63 TC 56 Z9 57 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 MAY 4 PY 1998 VL 187 IS 9 BP 1529 EP 1536 DI 10.1084/jem.187.9.1529 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZM112 UT WOS:000073505900017 PM 9565644 ER PT J AU Adcock, DM Kressin, DC Marlar, RA AF Adcock, DM Kressin, DC Marlar, RA TI Minimum specimen volume requirements for routine coagulation testing - Dependence on citrate concentration SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE coagulation testing; prothrombin time [PT]; activated partial thromboplastin time [APTT]; sample volume; sodium citrate concentration AB We evaluated the effect of sample volume and citrate concentration on results of routine coagulation assays (prothrombin time [PT] and activated partial thromboplastin time [APTT]). The study was performed on samples obtained from healthy persons and patients receiving oral anticoagulant therapy. Standard evacuated tubes (3.2% and 3.8% sodium citrate) were filled to varying total sample volumes ranging from 3.0 to 5.0 mL, and results of routine coagulation tests were compared. Underfilling may significantly affect the APTT and PT resulting in artifactual prolongation of results. This effect is most pronounced in samples drawn into 3.8% citrate. By using 3.8% citrate, there is a statistically significant difference in the results of PT assays in the samples less than 80% filled compared with those that are 100% filled. For APTT assays performed on samples drawn into 3.8% citrate, a statistical difference occurred at less than 90% filled. This effect was less pronounced when samples were drawn into 3.2% sodium citrate. Ve found no statistically significant difference in PT results from a 3.2% citrate tube between fill volumes of 60% and 100% and none for APTT results between fill volumes of 70% and 100%. This study further supports the recommendation to use 3.2% sodium citrate concentration, because 60% of the optimum filled volume for PT and 70% of the optimum filled volume for APTT are acceptable. C1 Denver VA Med Ctr, Pathol & Lab Med, Lab Serv 113, Denver, CO 80220 USA. Colorado Permanente Med Grp, Dept Pathol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. RP Marlar, RA (reprint author), Denver VA Med Ctr, Pathol & Lab Med, Lab Serv 113, 1055 Clermont St, Denver, CO 80220 USA. NR 7 TC 54 Z9 56 U1 1 U2 6 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 1998 VL 109 IS 5 BP 595 EP 599 PG 5 WC Pathology SC Pathology GA ZK068 UT WOS:000073281700016 PM 9576579 ER PT J AU Rao, PM Sagarin, MJ McCabe, CJ AF Rao, PM Sagarin, MJ McCabe, CJ TI Stump appendicitis diagnosed preoperatively by computed tomography SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE appendicitis; appendix; computed tomography (CT) ID LAPAROSCOPIC APPENDECTOMY; RECURRENT APPENDICITIS; ABSCESS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 12 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD MAY PY 1998 VL 16 IS 3 BP 309 EP 311 DI 10.1016/S0735-6757(98)90110-3 PG 3 WC Emergency Medicine SC Emergency Medicine GA ZM423 UT WOS:000073538700024 PM 9596441 ER PT J AU Dasani, BM Sigal, SH Lieber, CS AF Dasani, BM Sigal, SH Lieber, CS TI Analysis of risk factors for chronic hepatic encephalopathy: The role of Helicobacter pylori infection SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PORTAL-SYSTEMIC ENCEPHALOPATHY; CONTROLLED TRIAL; BREATH TEST; AMMONIA; UREA; CIRRHOSIS; HYPERAMMONEMIA; LACTULOSE; NEOMYCIN; PREVALENCE AB Objective: Elevated blood ammonia is an important pathogenic factor of hepatic encephalopathy. Although colonic bacteria are considered the main source of ammonia, the stomach in subjects with urease-producing Helicobacter pylori (H. pylori) is an alternative site. The objective of this study was to determine whether H. pylori is associated with this complication. Methods: After assessing liver function and portal hypertension, 55 cirrhotics were evaluated for encephalopathy and H. pylori infection. Response to 2 weeks of amoxicillin (2 g/day) and omeprazole (40 mg/day) was then assessed in 17 (13 H. pylori-positive, four H. pylori-negative) encephalopathic subjects. Results: H. pylori infection was more common (67% vs 33%, p = 0.004) among encephalopathic patients. Additional factors associated with encephalopathy included older age (60.1 +/- 1.5 vs 49.8 +/- 2.4 yr, p = 0.001), lower albumin (3.17 +/- 0.08 vs 3.69 +/- 0.12 g/dl, p = 0.001), higher total bilirubin (2.24 +/- 0.20 vs 1.53 +/- 0.23 mg/dl, p = 0.034), greater ascites score (0.8 +/- 0.1 vs 0.3 +/- 0.1, p = 0.01), greater diuretic score (1.1 +/- 0.1 vs 0.3 +/- 0.1, p = 0.002), and greater modified Child score (6.7 +/- 0.3 vs 5.1 +/- 0.3, p = 0.001), When adjusted for severity of cirrhosis and age, H. pylori continued to demonstrate a statistical association (p = 0.039), After anti-H. pylori therapy, symptomatology in infected encephalopathic patients appeared to improve, whereas noninfected subjects were unaffected. Conclusion: in cirrhotic patients, H. pylori infection is associated with hepatic encephalopathy, especially in younger patients with decompensated liver disease. (C) 1998 by Am. Coll. of Gastroenterology. C1 Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Ctr Alcohol Res & Treatment, Sect Liver Dis & Nutr, Bronx, NY 10468 USA. RP Lieber, CS (reprint author), Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Ctr Alcohol Res & Treatment, Sect Liver Dis & Nutr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIAAA NIH HHS [AA03508, AA07275] NR 47 TC 37 Z9 43 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 1998 VL 93 IS 5 BP 726 EP 731 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZR482 UT WOS:000073981400012 PM 9625117 ER PT J AU Rabkin, JM Corless, CL Orloff, SL Benner, KG Flora, KD Rosen, HR Olyaei, AJ AF Rabkin, JM Corless, CL Orloff, SL Benner, KG Flora, KD Rosen, HR Olyaei, AJ TI Liver transplantation for disulfiram-induced hepatic failure SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ALCOHOL; DISEASE AB Fulminant hepatitis is a rare but potentially fatal adverse reaction that may occur after the use of disulfiram, A patient without a known history of liver disease was transplanted for fulminant hepatic failure secondary to disulfiram. A high index of suspicion and aggressive therapeutic approaches are essential for the prompt diagnosis and treatment of disulfiram-induced hepatic failure. The clinical presentation, histopathology, treatment, and all cases of disulfiram-induced hepatic failure reported in the English Literature are reviewed. The role of orthotopic li cer transplantation in a case of disulfiram-induced hepatic failure is discussed. (C) 1998 by Am. Cell. of Gastroenterology. C1 Oregon Hlth Sci Univ, Dept Surg, Sect Liver Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Rabkin, JM (reprint author), Sect Liver Pancreas Transplantat, 3181 SW Sam Jackson Pk Rd,L590, Portland, OR 97201 USA. NR 10 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAY PY 1998 VL 93 IS 5 BP 830 EP 831 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZR482 UT WOS:000073981400033 PM 9625138 ER PT J AU Eng, C Ji, HL AF Eng, C Ji, HL TI Molecular classification of the inherited hamartoma polyposis syndromes: Clearing the muddied waters SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material ID CHROMOSOME C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Translat Res Lab, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge, England. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Genet, Seattle, WA USA. RP Eng, C (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Translat Res Lab, Charles A Dana Human Canc Genet Unit, 1 Jimmy Fund Way,SM 822, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 NR 20 TC 60 Z9 60 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 1998 VL 62 IS 5 BP 1020 EP 1022 DI 10.1086/301847 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA ZL922 UT WOS:000073487000004 PM 9545417 ER PT J AU Neto, JFL Lu, L Eavey, RD Flores, MAM Caldera, RM Sangwatanaroj, S Schott, JJ McDonough, B Santos, JI Seidman, CE Seidman, JG AF Neto, JFL Lu, L Eavey, RD Flores, MAM Caldera, RM Sangwatanaroj, S Schott, JJ McDonough, B Santos, JI Seidman, CE Seidman, JG TI The Bjornstad syndrome (sensorineural hearing loss and pili torti) disease gene maps to chromosome 2q34-36 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DEAFNESS; LOCALIZATION; PROTEINS AB We report that the Bjornstad syndrome gene maps to chromosome 2q34-36. The clinical association of sensorineural hearing Loss with pili torti (broken, twisted hairs) was described >30 years ago by Bjornstad; subsequently, several small families have been studied. We evaluated a large kindred with Bjornstad syndrome in which eight members inherited pill torti and prelingual sensorineural hearing loss as autosomal recessive traits. A genomewide search using polymorphic loci demonstrated linkage between the disease gene segregating in this kindred and D2S434 (maximum two-point LOD score = 4.98 at theta = 0). Haplotype analysis of recombination events located the disease gene in a 3-cM region between loci D2S1371 and D2S163. We speculate that intermediate filament and intermediate filament-associated proteins are good candidate genes for causing Bjornstad syndrome. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Fundacao Fac Fed Ciencias Med Porto Alegre, Dept Ophtalmootorhinolaryngol, Porto Alegre, RS, Brazil. Complexo Hosp Santa Casa Porto Alegre, Otorhinolaryngol Serv, Porto Alegre, RS, Brazil. Univ Autonoma Zacatecas, Escuela Med, Zacatecas, Mexico. Natl Autonomous Univ Mexico, Dept Expt Med, Mexico City 04510, DF, Mexico. Natl Child Hlth Minist, Mexico City, DF, Mexico. RP Seidman, JG (reprint author), Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. RI Schott, jean-Jacques/F-8842-2013 NR 30 TC 13 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 1998 VL 62 IS 5 BP 1107 EP 1112 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZL922 UT WOS:000073487000015 ER PT J AU Poussaint, TY Kowal, JR Barnes, PD Zurakowski, D Anthony, DC Goumnerova, L Tarbell, NJ AF Poussaint, TY Kowal, JR Barnes, PD Zurakowski, D Anthony, DC Goumnerova, L Tarbell, NJ TI Tectal tumors of childhood: Clinical and imaging follow-up SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID BRAIN-STEM GLIOMAS; ONSET AQUEDUCTAL STENOSIS; PLATE GLIOMAS; MR; CHILDREN; MICROSURGERY; LESIONS; SCANS AB PURPOSE: This study was done to determine which clinical and imaging findings best correlate with outcome in children with tectal tumors. METHODS: A retrospective review was done of the medical records and imaging studies of 32 children (16 boys and 16 girls; mean age, 8 years) with tectal tumors. Eight children had CT, 11 had MR imaging, and 13 had both CT and MR studies. Findings from surgical and pathologic reports as well as from follow-up examinations (mean follow-up period, 5 years; range, 3.6 months to 17 years) were included in the review. RESULTS: All patients had hydrocephalus and all but one required CSF diversion. The tectum was the center of the tumor in all cases and the majority of the tumors appeared isodense on CT scans, isointense on T1-weighted MR images, and hyperintense on T2-weighted images. Twenty patients required no further treatment. In this group, the mean maximum tumor diameter was 1.8 cm and enhancement occurred in two cases. At follow-up, 18 patients had stable tumor size, one had an increase in tumor size with cyst formation but no worsening of symptoms, and one had a decrease in tumor size. Twelve patients required further treatment (excision and/or radiotherapy) because of progression as indicated by either increased tumor size or worsening of symptoms. In this group, the mean maximum tumor diameter was 2.5 cm and contrast enhancement occurred in nine cases. Further follow-up in this group showed decreased tumor size in eight and stable residual tumor in three. CONCLUSION: Tectal tumors in childhood have variable behavior. MR imaging assists in the clinical determination of which children need treatment beyond CSF diversion. Larger tumor size and enhancement are radiologic predictors of the need for further treatment. C1 Childrens Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02115 USA. Childrens Hosp, Dept Res Comp & Biostat, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Radiat Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Poussaint, TY (reprint author), Childrens Hosp, Dept Radiol, Div Neuroradiol, 300 Longwood Ave, Boston, MA 02115 USA. OI Anthony, Douglas/0000-0002-3815-2240 NR 27 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 1998 VL 19 IS 5 BP 977 EP 983 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZM904 UT WOS:000073588000036 PM 9613524 ER PT J AU Lim, KH Friedman, SA Ecker, JL Kao, L Kilpatrick, SJ AF Lim, KH Friedman, SA Ecker, JL Kao, L Kilpatrick, SJ TI The clinical utility of serum uric acid measurements in hypertensive diseases of pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE uric acid; preeclampsia; likelihood ratio ID PLASMA-URATE MEASUREMENTS; PRE-ECLAMPSIA AB OBJECTIVE: Our purpose was to evaluate the clinical utility of serum uric acid measurements in the hypertensive diseases of pregnancy. STUDY DESIGN: We performed a nested case-control study to assess the clinical utility of serum uric acid measurements in women with hypertensive diseases of pregnancy. We identified 344 women who had serum uric acid measurements at term and categorized them into five diagnostic groups according to definitions of hypertensive diseases in pregnancy published by the National Working Group on Hypertension in Pregnancy: transient hypertension of pregnancy (n = 69), preeclampsia (n = 130), chronic hypertension (n = 23), chronic hypertension with superimposed preeclampsia (n = 29), and normal (n = 93). We compared the mean uric acid concentration for each group with use of a one-way analysis of variance and Scheffe's post hoc test and calculated the sensitivities and specificities in diagnosing preeclampsia as well as the likelihood ratios for serum uric acid values of 5.5, 6.0, and 6.5 mg/dl. We also examined the correlation between serum uric acid levels and several clinical outcome measures in women with hypertensive diseases of pregnancy RESULTS: The mean serum uric acid values for women with preeclampsia (6.2 +/- 1.4 mg/dl) and transient hypertension (5.6 +/- 1.7 mg/dl) were significantly higher than those of controls (4.3 +/- 0.8 mg/dl, p < 0.05). The difference in mean serum uric acid values between women with chronic hypertension (4.9 +/- 1.0 mg/dl) and superimposed preeclampsia (5.8 +/- 1.4 mg/dl) were not statistically significant. The likelihood ratio of having preeclampsia with a serum uric acid value of 5.5 mg/dl was 1.41 in gestational hypertension of pregnancy and 2.5 in chronic hypertension. With use of a receiver-operator characteristic curve, we were unable to identify a serum uric acid value that could be used to differentiate various hypertensive diseases of pregnancy. There was a weak correlation between serum uric acid values and several clinical outcome measures of preeclampsia (r = 0.06 to 0.26). CONCLUSION: Although mean serum uric acid values are elevated in women with preeclampsia, the clinical utility of serum uric acid values in differentiating various hypertensive diseases of pregnancy appears to be limited. In the setting of chronic hypertension, however, a serum uric acid level of greater than or equal to 5.5 mg/dl could identify women with an increased likelihood of having superimposed preeclampsia. C1 Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Lim, KH (reprint author), Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. NR 23 TC 55 Z9 59 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 1998 VL 178 IS 5 BP 1067 EP 1071 DI 10.1016/S0002-9378(98)70549-6 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ZP972 UT WOS:000073807400033 PM 9609585 ER PT J AU Goke, M Kanai, M Podolsky, DK AF Goke, M Kanai, M Podolsky, DK TI Intestinal fibroblasts regulate intestinal epithelial cell proliferation via hepatocyte growth factor SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE coculture; mesenchyme; intestinal epithelial cell growth; c-met ID TYROSINE KINASE; PRIMARY CULTURE; MET ONCOGENE; FACTOR-ALPHA; RECEPTOR; DIFFERENTIATION; EXPRESSION; MIGRATION; MOUSE; RATS AB Although the presence of subepithelial intestinal fibroblasts has been well recognized, the effects of fibroblasts on intestinal epithelial cell (IEC) growth are incompletely understood. In vitro studies were undertaken to evaluate the effects of fibroblasts on the proliferation of model IEC lines. IECs (Caco-2, T84, and IEC-B) were grown alone or in the presence of human intestinal (CCD-18), lung (CCD-37), or skin explant-derived fibroblasts. Cocultures were carried out directly on irradiated fibroblasts or by Transwell coculture technique with fibroblasts and epithelial cells separated by a porous filter. Cell proliferation was assessed by [H-3]thymidine incorporation and cell counts. Hepatocyte growth factor (HGF) and c-met transcript expression in IECs and fibroblasts was examined by RT-PCR and Northern blotting; protein expression was evaluated by immunoblotting. Intestinal as well as lung and skin fibroblasts substantially stimulated proliferation of Caco-2, T84, and IEC-B cells in both direct and Transwell cocultures. In addition, fibroblast-conditioned medium stimulated IEC proliferation, suggesting a paracrine mechanism. Anti-human HGF-neutralizing antibodies blocked the growth-promoting effects in both fibroblasts and fibroblast-conditioned medium. Recombinant human HGF dose dependently promoted IEC proliferation. HGF mRNA and protein expression was restricted to fibroblasts. High levels of c-met expression were found in Caco-2 and T84 cells; in contrast. expression in fibroblasts was weak. In summary, fibroblasts stimulate IEC proliferation through a paracrine mechanism mediated predominantly by HGF. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ-719,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-43351, DK-41557] NR 56 TC 56 Z9 56 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 1998 VL 274 IS 5 BP G809 EP G818 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA ZM420 UT WOS:000073538300005 PM 9612260 ER PT J AU Martinez, V Barquist, E Rivier, J Tache, Y AF Martinez, V Barquist, E Rivier, J Tache, Y TI Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF(2) receptors SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE corticotropin-releasing factor; sauvagine; urotensin I; astressin; NBI-27914; CRF-(6-33); CRF antagonists; brain ID CORTICOTROPIN-RELEASING FACTOR; UROTENSIN-I; STRESS; SAUVAGINE; ANTAGONISTS; RESPONSES; BRAIN; CONTRACTILITY; EXPRESSION; TRANSIT AB Corticotropin-releasing factor (CRF)-related peptides exhibit different affinity for the receptor subtypes 1 and 2 cloned in the rat brain. We investigated, in conscious rats, the effects of intracisternal (IC) injection of CRF (rat/human) on the 5-h rate of gastric emptying of a solid nutrient meal (Purina chow and water ad libitum for 3 h) and the CRF receptor subtype involved. CRF, urotensin I (suckerfish), and sauvagine (frog) injected IC inhibited gastric emptying in a dose-dependent manner, with ED(50) values of 0.31, 0.13, and 0.08 mu g/rat, respectively. Rat CRF-(6-33) (0.1-10 mu g ic) had no effect. The nonselective CRF(1) and CRF(2) receptor antagonist, astressin, injected IC completely blocked the inhibitory effect of IC CRF, urotensin I, and sauvagine with antagonist-to-agonist ratios of 3:1, 10:1, and 16:1, respectively. The CRF(1)-selective receptor antagonist NBI-27914 injected IC at a ratio of 170:1 had no effect. These data show that central CRF and CRF-related peptides are potent inhibitors of gastric emptying of a solid meal with a rank order of potency characteristic of the CRF(2) receptor subtype affinity (sauvagine > urotensin I > CRF). In addition, the reversal by astressin but not by the CRF(1)-selective receptor antagonist further supports the view that the CRF(2) receptor subtype is primarily involved in central CRF-induced delayed gastric emptying. C1 W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92038 USA. Univ Rochester, Sch Med & Dent, Dept Surg, Rochester, NY 14642 USA. RP Tache, Y (reprint author), W Los Angeles Vet Affairs Med Ctr, Digest Dis Res Ctr, CURE, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-26741, DK-33061]; NIMH NIH HHS [MH-00663] NR 39 TC 70 Z9 70 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 1998 VL 274 IS 5 BP G965 EP G970 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA ZM420 UT WOS:000073538300024 PM 9612279 ER PT J AU Thompson, JT Rackley, MS O'Brien, TX AF Thompson, JT Rackley, MS O'Brien, TX TI Upregulation of the cardiac homeobox gene Nkx2-5 (CSX) in feline right ventricular pressure overload SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiac hypertrophy; pulmonary artery banding ID SERUM RESPONSE FACTOR; ALPHA-ACTIN GENE; MOLECULAR-CLONING; SKELETAL-MUSCLE; TINMAN HOMOLOG; MESSENGER-RNAS; HYPERTROPHY; HEART; NKX-2.5; DROSOPHILA AB The recent characterization of the cardiac-specific homeobox gene Nkx2-5 (or CSX) and its detection in normal adult heart tissue raises the possibility of a role in adult hypertrophy. Using pressure overload as a primary stimulus, we used a feline pulmonary artery banding model to produce right ventricular hypertrophy (RVH). Total RNA was hybridized to a full-length murine Nkx2-5 cDNA probe that contained the NK family homeodomain. Nkx2-5 mRNA levels increased 5.1-fold (P < 0.05) and 3.9-fold vs. the corresponding left ventricles at 2 and 7 days of RVH, respectively, during the period of maximal myocardial growth. By 2 wk, when the RVH response had been completed, Nkx2-5 mRNA levels were returning toward baseline. Hybridization with an Nks2-5 probe not containing the NK homologous homeodomain demonstrated that upregulation was specific for the Nks2-5 gene. Atrial natriuretic factor and alpha-cardiac actin, both activated in part by Nkx2-5 DNA binding elements, also increased with RVH. These data suggest that a cardiac homeobox gene may play a role in the induction of adult cardiac hypertrophy. C1 Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Off Res & Dev, Charleston, SC 29425 USA. Gazes Cardiac Res Inst, Charleston, SC 29425 USA. RP O'Brien, TX (reprint author), Med Univ S Carolina, Dept Med, Div Cardiol, 816 CSB,171 Ashley Ave, Charleston, SC 29425 USA. FU NHLBI NIH HHS [T32-HL-07260-19, HL-55284] NR 32 TC 42 Z9 44 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAY PY 1998 VL 274 IS 5 BP H1569 EP H1573 PG 5 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA ZM195 UT WOS:000073514200021 PM 9612365 ER PT J AU Tondo, L Baldessarini, RJ Hennen, J Floris, G AF Tondo, L Baldessarini, RJ Hennen, J Floris, G TI Lithium maintenance treatment of depression and mania in bipolar I and bipolar II disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LOW SERUM LEVELS; AFFECTIVE-ILLNESS; PROPHYLAXIS; UNIPOLAR; DISCONTINUATION; IMIPRAMINE; EFFICACY; STANDARD AB Objective: Effects of long-term lithium treatment for depressive and manic phases of type I and type II bipolar disorders were compared. Method: Clinical research records of 317 patients with DSM-IV-defined bipolar disorder (188 with type I and 129 with type II) were analyzed for frequency and duration of affective episodes and hospitalizations before (mean=8.38 years) versus during (mean=6.35 years) lithium maintenance treatment. Treatment effects were also assessed by survival analysis of interepisode intervals and by multivariate regression testing for factors associated with response to treatment. Results: Bipolar I and bipolar II patients were ill before treatment a similar Percentage of time, but the subtype distinction was supported descriptively. Lithium had superior benefits in type II patients, with significantly greater reduction of episodes per year and of the percentage of time ill. Reduction of depressive morbidity was similarly strong in both diagnostic types. During treatment, bipolar II patients had 5.9-fold longer interepisode intervals and were twice as likely as type I patients to have no new episodes. Starting lithium maintenance earlier predicted greater improvement. Conclusions: Lithium maintenance yielded striking long-term reductions of depressive as well as manic morbidity in both bipolar disorder subtypes, with greater overall benefits in type II patients and with earlier treatment. C1 Harvard Univ, Sch Med, Mailman Res Ctr,McLean Div Massachusetts Gen Hosp, Int Consortium Bipolar Disorder Res, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Mailman Res Ctr,McLean Div Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Mailman Res Ctr,McLean Div Massachusetts Gen Hosp, Neurosci Program, Cambridge, MA 02138 USA. Univ Cagliari, Dept Psychol, I-09124 Cagliari, Italy. Ctr Bini, Cagliari, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. FU NIMH NIH HHS [MH-47370] NR 50 TC 125 Z9 128 U1 0 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 1998 VL 155 IS 5 BP 638 EP 645 PG 8 WC Psychiatry SC Psychiatry GA ZL237 UT WOS:000073412500012 PM 9585715 ER PT J AU Spencer, T Biederman, J Wilens, T Prince, J Hatch, M Jones, J Harding, M Faraone, SV Seidman, L AF Spencer, T Biederman, J Wilens, T Prince, J Hatch, M Jones, J Harding, M Faraone, SV Seidman, L TI Effectiveness and tolerability of tomoxetine in adults with attention deficit hyperactivity disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID LONGITUDINAL DATA; DOUBLE-BLIND; PLACEBO; MODELS AB Objective: The authors assessed the experimental noradrenergic compound tomoxetine as an alternative treatment for adult attention deficit hyperactivity disorder (ADHD). Method: They conducted a double-blind, placebo-controlled, crossover study of tomoxetine in 22 adults with well-characterized ADHD. Results: Treatment with tomoxetine at an average oral dose of 76 mg/day was well tolerated. Drug-specific improvement in ADHD symptoms was highly significant overall and sufficiently robust to be detectable in a parallel-groups comparison restricted to the first 3 weeks of the protocol. Eleven of 21 patients showed improvement after receiving tomoxetine, compared with only two of 21 patients who improved after receiving placebo. Significant tomoxetine-associated improvement was noted on neuropsychological measures of inhibitory capacity from Stroop tests. Conclusions: This preliminary study showed that tomoxetine was effective in treating adult ADHD and was well tolerated. These promising results provide support for further studies of tomoxetine over an extended period of treatment. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Spencer, T (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 15 Parkman St,WACC 725, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-01169] NR 10 TC 230 Z9 233 U1 1 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 1998 VL 155 IS 5 BP 693 EP 695 PG 3 WC Psychiatry SC Psychiatry GA ZL237 UT WOS:000073412500022 PM 9585725 ER PT J AU Samuel, VJ Biederman, J Faraone, SV George, P Mick, E Thornell, A Curtis, S Taylor, A Brome, D AF Samuel, VJ Biederman, J Faraone, SV George, P Mick, E Thornell, A Curtis, S Taylor, A Brome, D TI Clinical characteristics of attention deficit hyperactivity disorder in African American children SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Academy-of-Child-and-Adolescent-Psychiatry CY OCT 22-27, 1996 CL PHILADELPHIA, PENNSYLVANIA SP Amer Acad Child & Adolescent Psychiat ID PSYCHIATRIC STATUS; COMORBIDITY; BOYS AB Objective: The authors' goal was to explore the nature of attention deficit hyperactivity disorder (ADHD) in African American children, which has received scant attention by psychiatric researchers. Method: Subjects were 19 African American children with DSM-III-R ADHD and 24 African American children without ADHD. Ethnically sensitive methods were used to evaluate the children comprehensively. The findings were compared with those from art earlier study of Caucasian children with ADHD. Results: African American children with ADHD had higher levels of psychiatric disorders other than ADHD than did African American children who did not have ADHD. Conclusions: Among African American children, ADHD may be characterized by a narrower pattern of psychiatric comorbidity and dysfunction than has been observed in Caucasians. Given the small number of subjects studied, these findings are preliminary and must be replicated to confirm their validity. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 15 Parkman St,WACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 10 TC 21 Z9 21 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 1998 VL 155 IS 5 BP 696 EP 698 PG 3 WC Psychiatry SC Psychiatry GA ZL237 UT WOS:000073412500023 PM 9585726 ER PT J AU Pitris, C Brezinski, ME Bouma, BE Tearney, GJ Southern, JF Fujimoto, JG AF Pitris, C Brezinski, ME Bouma, BE Tearney, GJ Southern, JF Fujimoto, JG TI High resolution imaging of the upper respiratory tract with optical coherence tomography - A feasibility study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID BIOPSY AB A need exists in respiratory medicine for a technology capable of identifying airway pathology on a micron scale. This study has demonstrated the feasibility of optical coherence tomography (OCT) for ultrahigh resolution imaging of the upper respiratory tract by in vitro studies of human tissue. OCT is a relatively new technique that can be used to noninvasively collect tomographic images of tissue microstructure with micron-scale resolution. OCT is analogous to ultrasound, measuring the intensity of infrared light rather than acoustical waves. Samples throughout the upper respiratory tract, from the epiglottis to the secondary bronchi, were imaged. The resulting images were compared with histopathology and verified the ability of OCT to delineate relevant structures such as the epithelium, mucosa, cartilage and its sublayers, and glands at a resolution higher than any clinical imaging technology. The ability of OCT to generate image resolution in the range close to that of histopathology in real time, as well as easy integration with small, relatively inexpensive endoscopes, low cost, and lack of a need for a transducing medium, supports the hypothesis that this optical technology could become a powerful modality in the diagnosis and management of a wide range of clinical respiratory pathology. C1 MIT, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brezinski, ME (reprint author), 50 Vassar St,Room 36-357, Cambridge, MA 02139 USA. OI Pitris, Costas/0000-0002-5559-1050 FU NCI NIH HHS [NIH-9-RO1-CA75289-01]; NEI NIH HHS [NIH-9-RO1-EY11289-10]; NHLBI NIH HHS [H1H-1-R29-HL55686-01A1] NR 16 TC 61 Z9 66 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY PY 1998 VL 157 IS 5 BP 1640 EP 1644 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZM736 UT WOS:000073570700041 PM 9603149 ER PT J AU Ryan, JM Murphy, BL Boland, GW Mueller, PR AF Ryan, JM Murphy, BL Boland, GW Mueller, PR TI Use of the transgluteal route for percutaneous abscess drainage in acute diverticulitis to facilitate delayed surgical repair SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID DEEP PELVIC ABSCESSES; TRANSVAGINAL DRAINAGE; TRANSRECTAL DRAINAGE; FLUID COLLECTIONS; GUIDED DRAINAGE C1 Allegheny Univ Hosp, Dept Radiol, Div Anglointervent Radiol, Philadelphia, PA 19102 USA. Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ryan, JM (reprint author), Allegheny Univ Hosp, Dept Radiol, Div Anglointervent Radiol, Philadelphia, PA 19102 USA. NR 12 TC 16 Z9 16 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1998 VL 170 IS 5 BP 1189 EP 1193 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ823 UT WOS:000073257300009 PM 9574582 ER PT J AU Ramsdell, MG Chew, FS Keel, SB AF Ramsdell, MG Chew, FS Keel, SB TI Myxoid liposarcoma of the thigh SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Chew, FS (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1998 VL 170 IS 5 BP 1242 EP 1242 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ823 UT WOS:000073257300020 PM 9574593 ER PT J AU Rao, PM Mueller, PR AF Rao, PM Mueller, PR TI Clinical and pathologic variants of appendiceal disease: CT features SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ULCERATIVE-COLITIS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 9 TC 25 Z9 26 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1998 VL 170 IS 5 BP 1335 EP 1340 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ823 UT WOS:000073257300039 PM 9574612 ER PT J AU De Sanctis, JT Connolly, SA Bramson, RT AF De Sanctis, JT Connolly, SA Bramson, RT TI Effect of patient position on sonographically measured renal length in neonates, infants, and children SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID KIDNEY LENGTH; ULTRASOUND; SIZE AB OBJECTIVE. Renal length as measured on sonography is Fundamental in the evaluation of renal disease in children. Understanding the effect of patient position and imaging plane on measured renal length is important for the appropriate use of the standards for interpretation, The goal of this study was to determine how measurement of renal length on sonograms is affected by changes in patient position and imaging plane. SUBJECTS AND METHODS. One hundred seventy-six neonates, infants, and children who were 2 days to 17 years old underwent sonography from October 1995 through June 1996. The largest long-axis renal dimension in sagittal, coronal, and prone planes was obtained for each kidney. Data were analyzed separately for each kidney to determine the individual variation of renal length. RESULTS. The correlation between maximum renal length on coronal, sagittal, and prone sonograms was greater than .95 for both right and left kidneys. The coronal plane yielded the largest measured renal length and the prone view, the smallest. The median of the absolute value of the differences between individual renal lengths as measured on sonograms in the different imaging planes was 2-3 mm for both left and right kidneys (mean difference, left kidney = 3.34-3.62 mm; mean difference, right kidney = 3.21-3.68 mm). CONCLUSION. The coronal and sagittal views yield the longest measurements and prone views, the shortest. Therefore, initial measurements should be made in coronal or sagittal planes. Prone views should be reserved for situations in which the suspicion exists that the kidney was foreshortened on other views. Reference standards done in a particular plane should be applicable in most situations regardless of the patient position necessary to obtain optimum length. C1 Massachusetts Gen Hosp, Dept Pediat Radiol, Boston, MA 02114 USA. RP De Sanctis, JT (reprint author), Massachusetts Gen Hosp, Dept Pediat Radiol, 34 Fruit St, Boston, MA 02114 USA. NR 11 TC 15 Z9 15 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1998 VL 170 IS 5 BP 1381 EP 1383 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ823 UT WOS:000073257300047 PM 9574620 ER PT J AU Rabkin, JM Orloff, SL Corless, CL Benner, KG Flora, KD Rosen, HR Keller, FS Barton, RE Lakin, PC Petersen, BD Saxon, RR Olyaei, AJ AF Rabkin, JM Orloff, SL Corless, CL Benner, KG Flora, KD Rosen, HR Keller, FS Barton, RE Lakin, PC Petersen, BD Saxon, RR Olyaei, AJ TI Hepatic allograft abscess with hepatic arterial thrombosis SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT North-Pacific-Surgical-Association 84th Annual Meeting CY NOV 14-15, 1997 CL PORTLAND, OREGON SP N Pacific Surg Assoc ID ORTHOTOPIC LIVER-TRANSPLANTATION; VASCULAR COMPLICATIONS; CLINICAL PRESENTATION; EXPERIENCE AB BACKGROUND: Intrahepatic abscess (IA) is an uncommon complication after liver transplantation (OLTx) usually found in the setting of hepatic arterial thrombosis (HAT) often with associated biliary tree necrosis and/or stricture. Conventional treatment of IA in this setting has required retransplantation. METHODS: A retrospective review of 274 patients (287 OLTx) from September 1991 through September 1996 was performed. Median follow-up was 3.6 years. Diagnosis of HAT was confirmed by arteriography and IA was documented by computerized tomography. Percutaneous drainage of the abscess and stenting of biliary strictures, if present, was achieved using conventional interventional radiology techniques. RESULTS: The diagnosis of hepatic artery complication was made in 14 patients (5.1%), 2 of whom required retransplantation. Hepatic artery thrombosis associated with solitary IA was found in 3 patients (1%) who were transplanted in our center and in 1 additional patient followed up at our center but transplanted elsewhere. All 4 patients had complete resolution of IA using this approach. Three of the 4 patients are alive and well, with the fourth patient succumbing to recurrent hepatitis B infection resulting in allograft failure. CONCLUSIONS: Solitary hepatic allograft abscesses associated with HAT respond to percutaneous drainage and antibiotics, obviating the need for retransplantation in this setting. (C) 1998 by Excerpta Medica, Inc. C1 Oregon Hlth Sci Univ, Dept Surg, Sect Liver Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Radiol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Rabkin, JM (reprint author), Oregon Hlth Sci Univ, Sect Liver Pancreas Transplantat, 3181 SW Sam Jackson Pk Rd,L590, Portland, OR 97201 USA. NR 34 TC 27 Z9 34 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 1998 VL 175 IS 5 BP 354 EP 359 DI 10.1016/S0002-9610(98)00051-8 PG 6 WC Surgery SC Surgery GA ZM410 UT WOS:000073537000003 PM 9600276 ER PT J AU Robertson, D DesJardin, JA Lichtenstein, MJ AF Robertson, D DesJardin, JA Lichtenstein, MJ TI Distribution and observed associations of orthostatic blood pressure changes in elderly general medicine outpatients SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE blood pressure; heart failure; autonomic; hypotension; syncope ID POSTURAL HYPOTENSION; PREVALENCE; QUESTIONNAIRE; HYPERTENSION; HEALTH; SYSTEM; FALLS; AGE AB Factors associated with orthostatic blood pressure change in elderly outpatients were determined by surveying 398 medical clinical outpatients aged 65 years and older. Blood pressure was measured with random-zero sphygmomanometers after patients were 5 minutes in a supine and 5 minutes in a standing position. Orthostatic blood pressure changes were at normally distributed levels with systolic and diastolic pressures dropping an average of 4 mm Hg (standard deviation [SD] = 15 mm Hg) and 2 mm Hg (SD = 11 mm Hg), respectively. Orthostatic blood pressure changes were unassociated with age, race, sex, body mass, time since eating, symptoms, or other factors. According to multiple linear regression analysis, supine systolic pressure, chronic obstructive pulmonary disease (COPD), and diabetes mellitus were associated with a decrease in systolic pressure on standing. Hypertension, antiarthritic drugs, and abnormal heartbeat were associated with an increase in systolic pressure on standing. For orthostatic diastolic pressure changes, supine diastolic pressure and COPD were associated with a decrease in diastolic pressure on standing. Congestive heart failure was associated with an increase in standing diastolic pressure. Using logistic regression analysis, only supine systolic pressure was associated with a greater than 20-mm Hg drop in systolic pressure (n = 53, prevalence = 13%). Supine diastolic pressure and COPD mere the only variables associated with a greater than 20-mm Hg drop in diastolic pressure (n = 16, prevalence = 4%). These factors may help physicians in identifying older persons at risk for having orthostatic hypotension. C1 Vanderbilt Univ, Auton Dysfunct Ctr, Nashville, TN 37232 USA. Audie L Murphy Mem Vet Hosp, Geriatr Res Educ & Clin Ctr, San Antonio, TX 78284 USA. RP Robertson, D (reprint author), Vanderbilt Univ, Auton Dysfunct Ctr, AA-3228 Med Ctr N, Nashville, TN 37232 USA. FU NCRR NIH HHS [RR00095]; NHLBI NIH HHS [HL56373]; NINDS NIH HHS [NS33460] NR 45 TC 14 Z9 14 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAY PY 1998 VL 315 IS 5 BP 287 EP 295 DI 10.1097/00000441-199805000-00001 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA ZK781 UT WOS:000073362900001 PM 9587084 ER PT J AU Aoki, M Lin, CLG Rothstein, JD Geller, BA Hosler, BA Munsat, TL Horvitz, HR Brown, RH AF Aoki, M Lin, CLG Rothstein, JD Geller, BA Hosler, BA Munsat, TL Horvitz, HR Brown, RH TI Mutations in the glutamate transporter EAAT2 gene do not cause abnormal EAAT2 transcripts in amyotrophic lateral sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID AMINO-ACID TRANSPORTER; N-LINKED GLYCOSYLATION; HUMAN GENOME; RAT-BRAIN; SUPEROXIDE-DISMUTASE; MAP; LINKAGE; CLONING; LOCALIZATION; EXPRESSION AB Recently, variant mRNA transcripts for the astroglial glutamate transporter EAAT2 have been detected in brain tissues of 60% of patients with sporadic amyotrophic lateral sclerosis (SALS). We have tested the hypothesis that the gene for EAAT2 may be defective in some ALS cases. In 16 familial ALS (FALS) pedigrees without mutations in SOD1, we failed to detect genetic linkage to the EAAT2 locus. We next characterized the genomic organization of the EAAT2 gene and used single-strand conformation polymorphism analysis of genomic DNA to identify one novel mutation in a single SALS patient and two novel mutations in 2 affected FALS siblings. In the SALS patient, the mutation substitutes serine for an asparagine that might be involved in N-linked glycosylation of the EAAT2 protein. In the 2 affected individuals in the FALS family, we detected both a mutation in the 5' end of intron 7 and a silent G --> A transition at codon 234 in exon 5. It remains unclear whether this intron 7 mutation is related to the defective mRNA splicing. These studies indicate that germline mutations in the EAAT2 gene are infrequent and do not explain the presence of variant mRNA transcripts of EAAT2 in more than one-half of ALS cases. C1 Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Charlestown, MA USA. MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA USA. Tufts Univ, New England Med Ctr, Dept Neurol, Boston, MA 02111 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. RP Brown, RH (reprint author), Massachusetts Gen Hosp East, Cecil B Day Lab Neuromuscular Res, Room 6627,Bldg 149,13th St,Navy Yard, Charlestown, MA 02129 USA. RI rothstein, jeffrey/C-9470-2013; Lin, Chien-liang/E-3513-2011 FU AHRQ HHS [5F32HS10064]; NIA NIH HHS [1PO1AG12992-02]; NINDS NIH HHS [1PO1NS31248-02] NR 44 TC 91 Z9 94 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1998 VL 43 IS 5 BP 645 EP 653 DI 10.1002/ana.410430514 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZL147 UT WOS:000073403500013 PM 9585360 ER PT J AU Augood, SJ Penney, JB Friberg, IK Breakefield, XO Young, AB Ozelius, LJ Standaert, DG AF Augood, SJ Penney, JB Friberg, IK Breakefield, XO Young, AB Ozelius, LJ Standaert, DG TI Expression of the early-onset torsion dystonia gene (DYT1) in human brain SO ANNALS OF NEUROLOGY LA English DT Article ID MESSENGER-RNA; PROTEINS AB Early-onset torsion dystonia, an autosomal dominant disease associated with the DYT1 locus on 9q34, is the most frequent genetic form of dystonia. Recent work has revealed that the causative mutation in most cases is deletion of a glutamate residue from the carboxy terminal of torsinA, a 332 amino acid protein encoded by the DYT1 gene. To gain insight into how deletion of a single amino acid can produce such a profound movement disorder, we have mapped the expression of the DYT1 gene in normal human postmortem brain. DYT1 mRNA is highly enriched in the dopamine neurons of the substantia nigra pars compacta Intense expression was also found in the cerebellum and hippocampal subfields. The prominent expression of the DYT1 gene within the substantia nigra pars compacta, which provides dopaminergic innervation to the basal ganglia, implicates a disturbance of dopaminergic function in the pathophysiology of early-onset torsion dystonia. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Genet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Neurol Serv, Warren 408, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NIMH NIH HHS [MH/NS 31862]; NINDS NIH HHS [NS28384, NS31579] NR 16 TC 79 Z9 83 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1998 VL 43 IS 5 BP 669 EP 673 DI 10.1002/ana.410430518 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZL147 UT WOS:000073403500017 PM 9585364 ER PT J AU Goldhirsch, A Colleoni, M Coates, AS Castiglione-Gertsch, M Gelber, RD AF Goldhirsch, A Colleoni, M Coates, AS Castiglione-Gertsch, M Gelber, RD CA Int Breast Canc Study Grp TI Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: Are all CMFs alike? SO ANNALS OF ONCOLOGY LA English DT Editorial Material DE adjuvant chemotherapy; breast cancer; CMF; radiotherapy; tamoxifen ID POSITIVE BREAST-CANCER; INTRAVENOUS CMF; FOLLOW-UP; CYCLOPHOSPHAMIDE; POSTMENOPAUSAL; METHOTREXATE; FLUOROURACIL AB The first reported effective adjuvant combination regimen for patients with operable breast cancer comprised oral cyclophosphamide (C) days 1-14 with intravenous methotrexate (M) and fluorouracil (F) on days 1 and 8, repeated every 28 days ('classical' CMF). These drugs have since been extensively used with or without endocrine therapies and/or other cytotoxics, as well as with radiation therapy to the chest wall yielding conflicting results. Although doses and schedules have varied widely, the combination of these three drugs has been generically referred to as CME Evidence exists that reducing the dose andior altering the schedule of CMF ('modified' CMF) have compromised its efficacy in metastatic breast cancer. Reduction below standard dose of a similar regimen also gave inferior results in the adjuvant setting. In fact, the recently reported improved outcome of adding radiation therapy to CMF was only demonstrated in comparisons with a 'modified' CME Furthermore, trials in women with estrogen receptor-positive breast cancer. which did not demonstrate any significant benefit for the addition of adjuvant CMF to tamoxifen compared with tamoxifen alone, also used 'modified' CMF. Therefore, adherence to the 'classical' dose and schedule is recommended when CMF is used in adjuvant therapy. C1 European Inst Oncol, Int Breast Canc Study Grp, Dept Med Oncol & Radiat Oncol, Dept Med Oncol, I-20141 Milan, Italy. Univ Sydney, Dept Med, Royal Prince Alfred Hosp, Australian New Zealand Breast Canc Trials Grp, Sydney, NSW 2006, Australia. Int Breast Canc Study Grp, Coordinat Ctr, Bern, Switzerland. Frontier Sci & Technol Res Fdn, Boston, MA USA. Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. RP Goldhirsch, A (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Dept Med Oncol & Radiat Oncol, Dept Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM agoldhirsch@sakk.ch FU NCI NIH HHS [CA-75362] NR 25 TC 36 Z9 36 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAY PY 1998 VL 9 IS 5 BP 489 EP 493 DI 10.1023/A:1008236502420 PG 5 WC Oncology SC Oncology GA ZV937 UT WOS:000074357200010 PM 9653488 ER PT J AU Hillman, RE Walsh, MJ Fisher, SG Wolf, GT Hong, WK AF Hillman, RE Walsh, MJ Fisher, SG Wolf, GT Hong, WK TI Functional outcomes following treatment for advanced laryngeal cancer - Part I Voice preservation in advanced laryngeal cancer - Part II Laryngectomy rehabilitation: The state of the art in the VA system SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Review DE advanced laryngeal cancer; artificial larynx; esophageal speech; functional outcomes; laryngeal preservation; laryngectomy; swallowing; tracheoesophageal speech ID SECONDARY TRACHEOESOPHAGEAL PUNCTURE; QUALITY-OF-LIFE; NECK-CANCER; ARTIFICIAL LARYNX; INDUCTION CHEMOTHERAPY; ESOPHAGEAL SPEECH; ADVANCED HEAD; PERCEPTUAL CHARACTERISTICS; ELECTROLARYNGEAL SPEECH; ACCEPTABILITY RATINGS AB This two-part investigation assessed functional outcomes related to communication (including amount of speech therapy), swallowing and eating, and employment status for patients who received one of the two treatment modalities for advanced laryngeal cancer (stage III or IV laryngeal squamous cell carcinoma) in Veterans Administration Cooperative Study #268. One hundred sixty-six patients were randomized to primary surgery (laryngectomy) and radiotherapy (RT), and 166 to induction chemotherapy (CT) and RT. The first investigation dealt with examining and comparing functional outcomes for patients in the two treatment arms of the main study. Results showed clearly that patients with advanced laryngeal cancer are better off from the standpoint of speech communication if they can be treated for this disease without removal of the larynx. In contrast, there were few significant differences between patient groups for other non-speech-related measures. The second investigation focused on communication-related outcomes associated with the rehabilitation of total laryngectomy patients. Results revealed that only relatively small percentages of total laryngectomy patients (6%) developed usable esophageal speech or remained nonvocal (8%), and that a majority of patients ended up as users of artificial electrolarynx (55%) or tracheoesophageal (31%) speech. The results from both investigations are discussed with respect to factors that can influence the rehabilitation process and long-term outcome status of patients who are treated for advanced laryngeal cancer with these two strategies. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Voice & Speech Lab,Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Dept Commun Sci & Disorders, Boston, MA 02114 USA. Boston VA Med Ctr, Audiol Speech Pathol Serv, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Univ Michigan, Dept Otolaryngol, Ann Arbor, MI 48109 USA. VA Cooperat Studies Program Coordinating Ctr, Hines, IL USA. MD Anderson Hosp, Dept Oncol, Houston, TX USA. RP Hillman, RE (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Voice & Speech Lab,Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 106 TC 22 Z9 22 U1 2 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 MAY PY 1998 VL 107 IS 5 SU 172 BP 2 EP 27 PN 2 PG 26 WC Otorhinolaryngology SC Otorhinolaryngology GA ZN066 UT WOS:000073605300001 ER PT J AU Duffy, FJ Concannon, MJ Gan, BS May, JW AF Duffy, FJ Concannon, MJ Gan, BS May, JW TI Late digital replantation failure: Pathophysiology and risk factors SO ANNALS OF PLASTIC SURGERY LA English DT Article ID MICROVASCULAR SURGERY; FREE-FLAP; VENOUS DRAINAGE; THROMBOSIS; VESSELS; TRAUMA; SOON AB It is generally accepted that replanted digits surviving at least 1 week following surgery rarely succumb to ischemic necrosis. Presented here are 2 patients who experienced late digital replantation failure. The first patient is an 8-year-old boy who had his index finger replanted at the proximal phalangeal level. After 16 days of viability, the replanted digit became swollen and subsequently necrosed. The second patient is a 35-year-old man with a history of smoking and intravenous drug use who underwent replantation of his avulsed thumb at the metacarpophalangeal joint. The replanted thumb was viable at the 2-week followup, but began to show ischemic changes at 3 weeks and eventually required revision amputation at the interphalangeal level. Both of these patients demonstrate late digital replantation failure-an unusual and poorly understood phenomenon. A discussion of possible risk factors and potential pathophysiology is presented. C1 Med City Dallas, Dallas, TX 75230 USA. Univ Missouri, Columbia, MO USA. Univ Toronto, Toronto Gen Hosp, Toronto, ON M5G 1L7, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Duffy, FJ (reprint author), Med City Dallas, 7777 Forest Lane,suite C700, Dallas, TX 75230 USA. NR 23 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD MAY PY 1998 VL 40 IS 5 BP 538 EP 541 DI 10.1097/00000637-199805000-00018 PG 4 WC Surgery SC Surgery GA ZL507 UT WOS:000073440400018 PM 9600443 ER PT J AU Fischer, CP Bode, BP Souba, WW AF Fischer, CP Bode, BP Souba, WW TI Adaptive alterations in cellular metabolism with malignant transformation SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 109th Annual Meeting of the Southern-Surgical-Association CY NOV 30-DEC 03, 1997 CL HOT SPRINGS, VIRGINIA SP So Surg Assoc ID GLUTAMINE TRANSPORT; PROTEIN-SYNTHESIS; TUMOR-GROWTH; CELLS; HEPATOMAS; INVIVO; ACID; HEPATOCYTE; RATS AB Objective The authors studied the differences between glutamine and glucose utilization in normal fibroblasts and in fibrosarcoma cells to gain insights into the metabolic changes that may ocour during malignant transformation. Summary Background Data The process of malignant transformation requires that cells acquire and use nutrients efficiently for energy, protein synthesis, and cell division. The two major sources of energy for cancer cells are glucose and glutamine. Glutamine is also essential for protein and DNA biosynthesis. We studied glucose and glutamine metabolism in normal and malignant fibroblasts, Methods Studies were done in normal rat kidney fibroblasts and in rat fibrosarcoma cells. We measured glutamine transport across the cell membrane, breakdown of glutamine by the enzyme glutaminase (the first step in oxidation), glutamine and glucose oxidation rates to CO2, rates of protein synthesis from glutamine, and glutamine-dependent growth rates. Results Glutamine transport rates were increased more than sixfold in fibrosarcomas compared to normal fibroblasts. In fibroblasts, glutamine transport was mediated by systems ASC and A. In malignant fibrosarcomas, only system ASC was identifiable, and its V-max was 15 times higher than that observed in fibroblasts. Despite an increase in transport, glutaminase activity was diminished and glutamine oxidation to CO2 was reduced in fibrosarcomas versus normal fibroblasts. In fibroblasts, glutamine oxidation was 1.8 times higher than glucose oxidation. In contrast, glucose oxidation was 3.5 times greater than glutamine oxidation in fibrosarcomas. Protein synthesis from glutamine transported by fibrosarcomas was threefold greater than that observed in normal fibroblasts. Despite marked increases in glutamine utilization and glucose oxidation in fibrosarcoma cells, growth rates were higher in the normal fibroblasts. Conclusions The process of malignant transformation is associated with a marked increase in cellular glutamine transport, which is mediated by a single high-affinity, high-capacity plasma membrane carrier protein. In normal fibroblasts, the transported glutamine is used primarily for energy production via oxidation of glutamine carbons to CO2. In fibrosarcomas, glutamine oxidation fails and glutamine is shunted into protein synthesis; simultaneously, the malignant cell switches to a glucose oxidizer. The increased glutamine transport and glucose oxidation in fibrosarcomas appears to be related to the malignant phenotype and not merely to an increase in cell growth rates. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Souba, WW (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Cox Bldg,Room 626,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA57690]; NIDDK NIH HHS [5 P30 DK 40561] NR 24 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 1998 VL 227 IS 5 BP 627 EP 636 DI 10.1097/00000658-199805000-00003 PG 10 WC Surgery SC Surgery GA ZM416 UT WOS:000073537800003 PM 9605654 ER PT J AU Fishman, JA AF Fishman, JA TI Prevention of infection due to Pneumocystis carinii SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; RENAL-TRANSPLANT RECIPIENTS; BONE-MARROW TRANSPLANTATION; RANDOMIZED CONTROLLED TRIAL; MAJOR SURFACE GLYCOPROTEIN; LOW-DOSE COTRIMOXAZOLE; TRIMETHOPRIM-SULFAMETHOXAZOLE; AEROSOLIZED PENTAMIDINE; PRIMARY PROPHYLAXIS; DAPSONE-PYRIMETHAMINE C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. EM jfishman@helix.mgh.harvard.edu NR 144 TC 57 Z9 58 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1998 VL 42 IS 5 BP 995 EP 1004 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA ZL001 UT WOS:000073388900001 PM 9593116 ER PT J AU Sasaki, T Amano, S Nishiyama, T Nakayama, Y Burgeson, RE Nakajima, H AF Sasaki, T Amano, S Nishiyama, T Nakayama, Y Burgeson, RE Nakajima, H TI Expression of laminin 5, and collagen IV and VII in bullous pemphigoid skin SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE laminin; collagen; bullous pemphigoid; basement membrane; immunohistochemistry ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MEMBRANE; AUTOANTIBODIES; IMMUNOFLUORESCENCE; DISEASES; KALININ; FAMILY; BIND C1 Yokohama City Univ, Sch Med, Dept Dermatol, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. Shiseido Res Ctr, Life Sci Res Labs, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Sasaki, T (reprint author), Yokohama City Univ, Sch Med, Dept Dermatol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 236, Japan. RI Nishiyama, Toshio/C-5434-2013 NR 15 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD MAY PY 1998 VL 290 IS 5 BP 283 EP 285 DI 10.1007/s004030050305 PG 3 WC Dermatology SC Dermatology GA ZW473 UT WOS:000074414500009 PM 9681681 ER PT J AU Morison, WL Baughman, RD Day, RM Forbes, PD Hoenigsmann, H Krueger, GG Lebwohl, M Lew, R Naldi, L Parrish, JA Piepkorn, M Stern, RS Weinstein, GD Whitmore, SE AF Morison, WL Baughman, RD Day, RM Forbes, PD Hoenigsmann, H Krueger, GG Lebwohl, M Lew, R Naldi, L Parrish, JA Piepkorn, M Stern, RS Weinstein, GD Whitmore, SE TI Consensus workshop on the toxic effects of long-term PUVA therapy SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ORAL METHOXSALEN-PHOTOCHEMOTHERAPY; NONMELANOMA SKIN-CANCER; 10-YEAR FOLLOW-UP; CUTANEOUS CARCINOMA; SEVERE PSORIASIS; ULTRAVIOLET-A; MALIGNANT-MELANOMA; EUROPEAN PUVA; TUMORS; PSORALENS AB The possibility that there is an increased risk of melanoma in patients with psoriasis treated with psoralen-UV-A (PUVA) therapy has raised concern on the part of physicians and patients about the long-term safety of this treatment. In response to this concern, the National Psoriasis Foundation sponsored a workshop at which invited participants with expertise in PUVA therapy, psoriasis treatment, melanoma and nonmelanoma skin cancer, and epidemiological and clinical trials were asked to develop a consensus on the following 3 issues: the risk of long-term adverse effects of PUVA therapy with emphasis on nonmelanoma and melanoma skin cancer; the guidelines for physicians and patients for selection and use of PUVA therapy with consideration of the risk-benefit ratio of this treatment compared with the risk-benefit ratios of alternative treatments; and the directions for further evaluation of the long-term effects of PUVA therapy. C1 Johns Hopkins Univ, Dept Dermatol, Baltimore, MD 21218 USA. Dartmouth Hitchcock Med Ctr, Dept Dermatol, Lebanon, NH 03766 USA. Univ Utah, Dept Dermatol, Salt Lake City, UT USA. Mt Sinai Med Ctr, Dept Dermatol, New York, NY 10029 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Univ Milan, Dept Dermatol, Bergamo, Italy. Univ Washington, Dept Dermatol, Seattle, WA 98195 USA. Univ Calif Irvine, Dept Dermatol, Irvine, CA 92717 USA. Clinicor Inc, Dept Dermatol, Austin, TX USA. Argus Res Labs Inc, Dept Dermatol, Horsham, PA USA. Univ Vienna, Sch Med, Div Special Dermatol, Vienna, Austria. RP Morison, WL (reprint author), Johns Hopkins Greenspring, 10753 Falls Rd,Suite 355, Lutherville, MD 21093 USA. RI Naldi, Luigi/K-6343-2016 OI Naldi, Luigi/0000-0002-3160-2835 NR 44 TC 80 Z9 82 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 1998 VL 134 IS 5 BP 595 EP 598 DI 10.1001/archderm.134.5.595 PG 4 WC Dermatology SC Dermatology GA ZN158 UT WOS:000073615700007 PM 9606329 ER PT J AU Woog, JJ Hartstein, ME Gliklich, R AF Woog, JJ Hartstein, ME Gliklich, R TI Paranasal sinus endoscopy and orbital fracture repair SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual American-Society-of-Ophthalmic-Plastic-and-Reconstructive-Surgery Meeting CY OCT 28, 1995 CL ATLANTA, GEORGIA SP Amer Soc Ophthalm Plast & Reconstruct Surg ID MANAGEMENT AB Although excellent results may be achieved in the management of many orbital floor injuries with standard transconjunctival or transcutaneous approaches, visualization of the posterior edge of the orbital floor or medial wall defect may be challenging at times. We describe our experience using endoscopic examination of the orbital floor through maxillary sinus approaches during the repair of selected orbital floor fractures. Owing to the posterosuperior angulation of the orbital floor, these approaches allow better visualization of the posterior edge of fractures involving the posterior portion of the orbital floor than do the standard transconjunctival approaches, and they facilitate confirmation that all orbital soft tissues have been elevated from the fracture site. We have used these techniques successfully in 9 patients with fractures involving either the posterior portion of the orbital floor or the medial wall or both. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. New England Eye Ctr, Boston, MA USA. RP Hartstein, ME (reprint author), 8729 Delmar,Suite 2W, St Louis, MO 63124 USA. NR 8 TC 16 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 1998 VL 116 IS 5 BP 688 EP 691 PG 4 WC Ophthalmology SC Ophthalmology GA ZM418 UT WOS:000073538100025 PM 9596514 ER PT J AU Chan, RJ Goodman, TA Aretz, TH Lie, JT AF Chan, RJ Goodman, TA Aretz, TH Lie, JT TI Segmental mediolytic arteriopathy of the splenic and hepatic arteries mimicking systemic necrotizing vasculitis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID FIBROMUSCULAR DYSPLASIA AB Segmental mediolytic arteriopathy, a rare, non-inflammatory arterial disease, is fundamentally a variant of fibromuscular dysplasia. The characteristic angiographic findings of segmental mediolytic arteriopathy include the "string of beads" and microaneurysms which are indistinguishable from those of vasculitis, and the correct diagnosis can be made only after histopathologic evaluation of the arterial lesions. Thrombosis, arterial wall hemorrhage, and dissection are among the complications of segmental mediolytic arteriopathy. We describe herein a patient with segmental mediolytic arteriopathy who presented with hemoperitoneum. The patient underwent urgent surgical repair of a ruptured hepatic artery aneurysm. The postoperative visceral arteriography findings led to a postoperative visceral arteriography findings led to a clinical diagnosis of polyarteritis nodosa, and immunosuppressive therapy was initiated. This treatment was stopped as soon as the correct biopsy diagnosis of segmental mediolytic arteriopathy was obtained through outside consultation. The patient recovered without drug treatment and was spared the potentially life-threatening complications of immunosuppression. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Arthrit Unit, Boston, MA 02114 USA. RP Chan, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Arthrit Unit, Bulfinch 165,55 Fruit St, Boston, MA 02114 USA. NR 10 TC 34 Z9 34 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1998 VL 41 IS 5 BP 935 EP 938 DI 10.1002/1529-0131(199805)41:5<935::AID-ART22>3.0.CO;2-N PG 4 WC Rheumatology SC Rheumatology GA ZL248 UT WOS:000073413600021 PM 9588747 ER PT J AU Neya, K Lee, R Vlahakes, GJ AF Neya, K Lee, R Vlahakes, GJ TI Hemoglobin based oxygen carrying solution stability in extracorporeal circulation - An in vitro evaluation and implications for clinical use SO ASAIO JOURNAL LA English DT Article ID AUTOLOGOUS BLOOD DONATION; OPEN-HEART-SURGERY; BOVINE HEMOGLOBIN; CARDIAC-SURGERY; OXIDATION; EFFICACY; METHEMOGLOBIN; TRANSFUSION; SUBSTITUTES; REDUCTION AB This study evaluated the stability of a hemoglobin based oxygen carrying (HBOC) solution during extracorporeal circulation. HBOC solution was diluted 1:1 with normal saline, 2 L of the resulting solution was oxygenated in either a bubble oxygenator (n = 5) or membrane oxygenator (n = 5), and it was placed in extracorporeal circulation at a rate of 2 L/min for 5 hr at 37 degrees C. To assess the effect of added human blood, 500 mi of fresh human whole blood was added to 1.5 L of diluted HBOC solution, and circulated as described. Methemoglobin level, hemoglobin integrity (percent of HBOC solution tetramer), and oxygen affinity (PO2 at 50% hemoglobin saturation) were measured. Extracorporeal circulation using the bubble oxygenator slightly altered (<1%) hemoglobin integrity compared with controls. Oxygen affinity decreased during extracorporeal circulation with both the membrane and bubble oxygenators; there was no significant difference between the oxygenators. Methemoglobin formation in controls and in extracorporeal circulation with either oxygenator was significant, with a slight advantage of the membrane compared with the bubble oxygenator; however, the presence of blood significantly decreased the rate of methemoglobin formation. In the presence of blood, HBOC solution remains structurally stable and efficacious for oxygen delivery during extracorporeal circulation. C1 Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Vlahakes, GJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, 55 Fruit St EDR105, Boston, MA 02114 USA. NR 21 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD MAY-JUN PY 1998 VL 44 IS 3 BP 166 EP 170 DI 10.1097/00002480-199805000-00008 PG 5 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA ZM899 UT WOS:000073587500008 PM 9617945 ER PT J AU Collins, CL Bode, BP Souba, WW Abcouwer, SF AF Collins, CL Bode, BP Souba, WW Abcouwer, SF TI Multiwell (CO2)-C-14-capture assay for evaluation of substrate oxidation rates of cells in culture SO BIOTECHNIQUES LA English DT Article ID METABOLISM; GLUCOSE; ACID AB (CO2)-C-14 capture is commonly used to evaluate the cellular oxidation rate of respiratory substrates. A modification of the established (CO2)-C-14-capture method was developed that enables the use of cells in adherent culture and easy analysis of multiple samples under different culture conditions. The use of commercially available culture and filter plates designed for use in a multiplate scintillation spectrophotometer enabled substrate oxidation rates to be evaluated for cells in a 24-well plate format without the need to dislodge the cells from the culture substrate as is required in traditional methods. Evaluation of radioactivity captured in potassium hydroxide-saturated filters was accomplished by adding scintillation fluid to the filter plate wells and counting. Alternatively, filters could be removed and placed in vials for evaluation in a conventional scintillation counter: This method was applied to the oxidation of C-14-glutamine by human breast cell lines and demonstrated concentration-dependent linear accumulation of captured counts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. RP Collins, CL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Cox 626,100 Blossom St, Boston, MA 02114 USA. OI Abcouwer, Steven F/0000-0003-2580-1288 FU NIDDK NIH HHS [P30-DK40561] NR 13 TC 15 Z9 15 U1 0 U2 6 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1998 VL 24 IS 5 BP 803 EP 808 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL759 UT WOS:000073468300021 PM 9591130 ER PT J AU Zhao, S Molnar, G Zhang, J Zheng, L Averboukh, L Pardee, AB AF Zhao, S Molnar, G Zhang, J Zheng, L Averboukh, L Pardee, AB TI 3 '-end cDNA pool suitable for differential display from a small number of cells SO BIOTECHNIQUES LA English DT Article ID LIBRARIES; CLONING; RNA AB We have generated a 3' cDNA pool from the RNA of only 1000 or fewer cells by reverse transcription (RT) from an extended oligo(dT) primer with a 3' degenerate base and a second strand primer with four degenerate 3' bases, followed by PCR. Reproducible differential displays (DD) can be made from this essentially inexhaustible source of DNA. The method produced DD patterns that are comparable but not identical in band number and size distribution with those obtained by the original RT-DD technique. Northern blots performed with the excised bands verified altered gene expressions. The data indicate that this St-end cDNA pool can supplement current PCR-based methods of expression genetics. This pool of cDNA sequences also provides a reliable source for primer-specific gene amplifications. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA61232] NR 13 TC 5 Z9 6 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1998 VL 24 IS 5 BP 842 EP + PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL759 UT WOS:000073468300028 PM 9591137 ER PT J AU Toner, M Buettner, H AF Toner, M Buettner, H TI Microfabrication in biology and medicine SO BIOTECHNOLOGY PROGRESS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Rutgers State Univ, Piscataway, NJ 08855 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAY-JUN PY 1998 VL 14 IS 3 BP 355 EP 355 DI 10.1021/bp980203f PG 1 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA ZT713 UT WOS:000074117200001 ER PT J AU Bhatia, SN Balis, UJ Yarmush, ML Toner, M AF Bhatia, SN Balis, UJ Yarmush, ML Toner, M TI Microfabrication of hepatocyte/fibroblast co-cultures: Role of homotypic cell interactions SO BIOTECHNOLOGY PROGRESS LA English DT Article ID ADULT-RAT HEPATOCYTES; EPITHELIAL-MESENCHYMAL INTERACTIONS; DIFFERENTIATED FUNCTIONS; SANDWICH CONFIGURATION; COLLAGEN SANDWICH; LIVER; GROWTH; EXPRESSION; COCULTURE; MATRIX AB Cell-cell interactions are important in embryogenesis, in adult physiology and pathophysiology of many disease processes. Co-cultivation of parenchymal and mesenchymal cells has been widely utilized as a paradigm for the study of cell-cell interactions in vitro. In addition, co-cultures of two cell types provide highly functional tissue constructs for use in therapeutic or investigational applications. The inherent complexity of such co-cultures creates difficulty in characterization of cell-cell interactions and their effects on function. In the present study, we utilize conventional "randomly distributed" co-cultures of primary rat hepatocytes and murine 3T3-J2 fibroblasts to investigate the role of increasing fibroblast density on hepatic function. In addition, we utilize microfabrication techniques to localize both cell populations in patterned configurations on rigid substrates. This technique allowed the isolation of fibroblast number as an independent variable in hepatic function. Notably, homotypic hepatocyte interactions were held constant by utilization of similar hepatocyte patterns in all conditions, and the heterotypic interface (region of contact between cell populations) was also held constant. Co-cultures were probed for synthetic and metabolic markers of liver-specific function. The data suggest that fibroblast number plays a role in modulation of hepatocellular response through homotypic fibroblast interactions. The response to changes in fibroblast number are distinct from those attributed to increased contact between hepatocytes and fibroblasts. This approach will allow further elucidation of the complex interplay between two cell types as they form a functional model tissue in vitro or as they interact in vivo to form a functional organ. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. RP Toner, M (reprint author), Shriners Res Ctr, 1 Kendall Sq,1400W, Cambridge, MA 02139 USA. EM mtoner@sbi.org RI Yu, weiting/I-7417-2013 NR 49 TC 192 Z9 199 U1 0 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAY-JUN PY 1998 VL 14 IS 3 BP 378 EP 387 DI 10.1021/bp980036j PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA ZT713 UT WOS:000074117200005 PM 9622518 ER PT J AU Folch, A Toner, M AF Folch, A Toner, M TI Cellular micropatterns on biocompatible materials SO BIOTECHNOLOGY PROGRESS LA English DT Article ID SELF-ASSEMBLED MONOLAYERS; MATERIALS SCIENCE; ADHESION; SURFACES; CELLS; GROWTH; HEPATOCYTES; FIBRONECTIN; CULTURE; CAPILLARIES AB We present a method to produce micropatterns of cells on tissue culture substrates. A network of deep elastomeric microchannels defining the desired pattern is sealed onto the surface of interest, and a protein template is created by injecting sub-milliliter quantities of protein solution into the microchannels. Protein adsorbs only on the areas that were exposed to the microflow. After the channels are flushed and the elastomer is removed, cells attach only on the protein template. Micropatterns of collagen or fibronectin were used to selectively adhere cells on various biomedical polymers and on heterogeneous or microtextured substrates. Since the bare substrate areas remain apt for seeding other, more adhesive cell types such as fibroblasts, we were able to create micropatterned co-cultures. Our method allows for inexpensive patterning of a rich assortment of biomolecules, cells, and surfaces under physiological conditions. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. RP Toner, M (reprint author), Shriners Res Ctr Bldg,1400 W,1 Kendall Sq, Cambridge, MA 02139 USA. NR 43 TC 196 Z9 201 U1 2 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAY-JUN PY 1998 VL 14 IS 3 BP 388 EP 392 DI 10.1021/bp980037b PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA ZT713 UT WOS:000074117200006 PM 9622519 ER PT J AU Carapeti, M Aguiar, RCT Goldman, JM Cross, NCP AF Carapeti, M Aguiar, RCT Goldman, JM Cross, NCP TI A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia SO BLOOD LA English DT Article ID ACTIVATION FUNCTION AF-2; CREB BINDING-PROTEIN; HUMAN GENOME; CBP; TRANSCRIPTION; ACETYLTRANSFERASE; SUPERFAMILY; MEDIATOR; COMPLEX; 8P11 AB Chromosomal abnormalities of band 8p11 are associated with a distinct subtype of acute myeloid leukemia with French-American-British M4/5 morphology and prominent erythrophagocytosis by the blast cells. This subtype is usually associated with the t(8;16)(p11;p13), a translocation that has recently been shown to result in a fusion between the MOZ and CBP genes. We have cloned the inv(8)(p11q13), an abnormality associated with the same leukemia phenotype, and found a novel fusion between MOZ and the nuclear receptor transcriptional coactivator TIF2/GRIP-1/NCoA-2. This gene has not previously been implicated in the pathogenesis of leukemia or other malignancies. MOZ-TIF2 retains the histone acetyltransferase homology domains of both proteins and also the CBP binding domain of TIF2, We speculate that the apparently identical leukemia cell phenotype observed in cases with the t(8;16) and the inv(8) arises by recruitment of CBP by MOZ-TIF2, resulting in modulation of the transcriptional activity of target genes by a mechanism involving abnormal histone acetylation, (C) 1998 by The American Society of Hematology. C1 Hammersmith Hosp, Imperial Coll, Sch Med, Dept Haematol, London W12 0NN, England. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Cross, NCP (reprint author), Hammersmith Hosp, Imperial Coll, Sch Med, Dept Haematol, Du Cane Rd, London W12 0NN, England. RI Cross, Nicholas/B-4817-2009 OI Cross, Nicholas/0000-0001-5481-2555 NR 44 TC 193 Z9 199 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1998 VL 91 IS 9 BP 3127 EP 3133 PG 7 WC Hematology SC Hematology GA ZJ995 UT WOS:000073274500005 PM 9558366 ER PT J AU Callus, BA Mathey-Prevot, B AF Callus, BA Mathey-Prevot, B TI Interleukin-3-induced activation of the JAK/STAT pathway is prolonged by proteasome inhibitors SO BLOOD LA English DT Article ID KAPPA-B-ALPHA; PROTEIN-TYROSINE-PHOSPHATASE; COLONY-STIMULATING FACTOR; INDUCED PHOSPHORYLATION; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAIN; IL-3 RECEPTOR; DNA-BINDING; KINASE; DEGRADATION AB One facet of cytokine receptor signaling involves the activation of signal transducers and activators of transcription (STATs). STATs are rapidly activated via tyrosine phosphorylation by Janus kinase (JAK) family members and subsequently inactivated within a short period. We investigated the effect of proteasome inhibition on interleukin-3 (IL-3) activation of the JAK/STAT pathway following stimulation of Ba/F-3 cells, Treatment of Ba/F-3 cells with the proteasome inhibitor, N-acetyl-L-leucinyl-L-leucinyl-norleucin (LLnL), led to stable tyrosine phosphorylation of the IL-3 receptor, beta common (pc), and STATE following stimulation. The effects of LLnL were not restricted to the JAK/STAT pathway, as Shc and mitogen-activated protein kinase (MAPK) phosphorylation were also prolonged in LLnL-treated cells. Further investigation showed these stable phosphorylation events were the result of prolonged activation of JAK2 and JAK1. These observations were confirmed using pharmacologic inhibitors. In the presence of LLnL, stable phosphorylation of STATE and pc was abrogated if the tyrosine kinase inhibitor, staurosporine, was added. The effect of staurosporine on STATE phosphorylation could be overcome if the phosphatase inhibitor, vanadate, was also added, suggesting phosphorylated STATE could be stabilized by phosphatase, but not by proteasome inhibition per se. These observations are consistent with the hypothesis that proteasome mediated protein degradation can modulate the activity of the JAK/STAT pathway by regulating the deactivation of JAK. (C) 1998 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Callus, BA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIDDK NIH HHS [P50 DK49216] NR 59 TC 53 Z9 53 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 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1998 VL 91 IS 9 BP 3182 EP 3192 PG 11 WC Hematology SC Hematology GA ZJ995 UT WOS:000073274500012 PM 9558373 ER PT J AU Dey, BR Yang, YG Szot, GL Pearson, DA Sykes, M AF Dey, BR Yang, YG Szot, GL Pearson, DA Sykes, M TI Interleukin-12 inhibits graft-versus-host disease through an Fas-mediated mechanism associated with alterations in donor T-cell activation and expansion SO BLOOD LA English DT Article ID EXPERIMENTAL VIRAL-INFECTIONS; INTERFERON-GAMMA-PRODUCTION; BONE-MARROW TRANSPLANTS; MONOCLONAL-ANTIBODIES; STIMULATORY FACTOR; LYMPHOCYTES-T; HELPER-CELLS; LEUKEMIA; IL-12; APOPTOSIS AB We have recently made the paradoxical observation that a single injection of recombinant murine interleukin-12 (IL-12) on the day of bone marrow transplantation (BMT) inhibits graft-versus-host disease (GVHD) in lethally irradiated mice receiving fully major histocompatability complex (MHC)mismatched bone marrow and spleen cells. We have now examined the mechanism of this effect of IL-12 on acute GVHD, By day 4 post-BMT, IL-12-treated mice showed marked reductions in splenic donor CD4(+) and CD8(+) T cells compared with GVHD controls. Expression of the early activation markers IL-2R alpha chain (CD25) and CD69 on splenic donor CD4(+) cells was considerably higher at early time points (36 and 72 hours post-BMT) in IL-12-treated mice compared with GVHD controls. However, the later, GVHD-associated increase in CD25 and very late antigen-4 (VLA-4) expression on donor T cells was greatly depressed in IL-12-protected mice compared with GVHD controls. The marked GVHD-associated expansion of host-reactive T helper cells by day 4 was also completely inhibited in the IL-12-treated group. Expression of Fas was increased on donor CD4 cells of IL-12-treated mice compared with those of controls on days 3 through 7 post-BMT. Furthermore, the ability of IL-12 to protect against GVHD was at least partially dependent on the ability of donor cells to express functional Fas molecules, We conclude that IL-12 treatment at the time of BMT markedly perturbs the activation of alloreactive donor CD4(+) T cells that play a critical role in the pathogenesis of acute GVHD, We hypothesize that these perturbations culminate in Fas-dependent apoptosis of donor T cells, thus impeding their expansion and their GVHD-promoting activity. (C) 1998 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Surg Serv,Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Surg Serv,Transplantat Biol Res Ctr, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [CA64912] NR 45 TC 50 Z9 50 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 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1998 VL 91 IS 9 BP 3315 EP 3322 PG 8 WC Hematology SC Hematology GA ZJ995 UT WOS:000073274500027 PM 9558388 ER PT J AU Martin, F van Deursen, JM Shivdasani, RA Jackson, CW Troutman, AG Ney, PA AF Martin, F van Deursen, JM Shivdasani, RA Jackson, CW Troutman, AG Ney, PA TI Erythroid maturation and globin gene expression in mice with combined deficiency of NF-E2 and Nrf-2 SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR NF-E2; LOCUS-CONTROL REGION; DOMINANT CONTROL REGION; HETEROZYGOUS BETA-THALASSEMIA; LEUCINE ZIPPER PROTEIN; EMBRYONIC STEM-CELLS; REGULATORY ELEMENT; ALPHA-THALASSEMIA; HYPERSENSITIVE SITE-3; ACTIVATION REGION AB NF-E2 binding sites, located in distant regulatory sequences, may be important for high level alpha- and beta-globin gene expression. Surprisingly, targeted disruption of each subunit of NF-E2 has either little or no effect on erythroid maturation in mice. For p18 NF-E2, this lack of effect is due, at least in part, to the presence of redundant proteins. For p45 NF-E2, one possibility is that NF-E2-related factors, Nrf-1 or Nrf-2, activate globin gene expression in the absence of NF-E2, To test this hypothesis for Nrf-2, we disrupted the Nrf-2 gene by homologous recombination. Nrf-2-deficient mice had no detectable hematopoietic defect. In addition, no evidence was found for reciprocal upregulation of NF-E2 or Nrf-2 protein in fetal liver cells deficient for either factor. Fetal liver cells deficient for both NF-E2 and Nrf-5 expressed normal levels of alpha- and beta-globin, Mature mice with combined deficiency of NF-E2 and Nrf-2 did not exhibit a defect in erythroid maturation beyond that seen with loss of NF-E2 alone. Thus, the presence of a mild erythroid defect in NF-E2-deficient mice is not the result of compensation by Nrf-2. (C) 1998 by The American Society of Hematology. C1 St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38101 USA. St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38101 USA. St Jude Childrens Res Hosp, Dept Expt Hematol, Memphis, TN 38101 USA. Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ney, PA (reprint author), St Jude Childrens Res Hosp, Dept Biochem, Room 4064,Thomas Tower,332 N Lauderdale, Memphis, TN 38101 USA. FU NCI NIH HHS [P30 CA21765] NR 57 TC 43 Z9 44 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 1 PY 1998 VL 91 IS 9 BP 3459 EP 3466 PG 8 WC Hematology SC Hematology GA ZJ995 UT WOS:000073274500044 PM 9558405 ER PT J AU Colby, C McAfee, SL Finkelstein, DM Spitzer, TR AF Colby, C McAfee, SL Finkelstein, DM Spitzer, TR TI Early vs delayed administration of G-CSF following autologous peripheral blood stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE granulocyte colony-stimulating factor (GCSF); hematopoietic recovery; autologous peripheral blood stem cell transplantation ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; GRANULOCYTE RECOVERY; NEUTROPHIL RECOVERY; RECONSTITUTION AB It is well established that recombinant human G-CSF accelerates neutrophil recovery following autologous peripheral blood stem cell transplantation (PBSCT). However, the optimal timing of G-CSF following transplantation remains unknown. We have conducted a retrospective analysis of patients treated with either early, day +1 (n = 42) or delayed, day +4 (n = 39) administration of G-CSF following autologous PBSCT for a variety of hematologic malignancies and solid tumors. G-CSF was given at a dose of 5 mu g/kg/day i.v. as a 2 h infusion beginning either day +1 or day +4 following PBSC infusion and continued until the total white blood count (WBC) was >10 x 10(9)/1. The numbers of transplanted CD34(+) cells were similar in each group. Treatment with early administration of G-CSF resulted in a significantly shorter time to an absolute neutrophil count (ANC) of >0.5x10(9)/1 (8.5 vs 10.0 days, P < 0.0003) and shorter length of hospitalization (16.3 vs 18.6 days, P < 0.0008), a trend towards a reduced incidence of infection (53 vs 72%) and a significant decrease in the duration of non-prophylactic antibiotic (NPA) therapy for neutropenic fever (4.0 vs 7.5 days, P < 0.009) compared to day +4 administration. Despite the additional cost of G-CSF, the reduction in the hospitalization and NPA therapy with early G-CSF administration resulted in 11% cost savings overall per transplant at our institution. C1 Massachusetts Gen Hosp, Bone Marrow Transplant Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Program, 55 Fruit St,FND 626, Boston, MA 02114 USA. NR 20 TC 25 Z9 25 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 1998 VL 21 IS 10 BP 1005 EP 1010 DI 10.1038/sj.bmt.1701203 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA ZN297 UT WOS:000073631800006 PM 9632273 ER PT J AU Waters, GS Rochon, E Caplan, D AF Waters, GS Rochon, E Caplan, D TI Task demands and sentence comprehension in patients with dementia of the Alzheimer's type SO BRAIN AND LANGUAGE LA English DT Article ID SYNTACTIC COMPREHENSION; SEMANTIC IMPAIRMENT; SENILE DEMENTIA; WORKING-MEMORY; DISEASE; LANGUAGE; CAPACITY; APHASIA; DISORDER; PATTERN AB Patients with dementia of the Alzheimer's type (DAT) and matched normal controls were given three tests of syntactic comprehension in which nonlinguistic visual and memory task demands were varied. In all tasks, subjects were presented spoken semantically reversible sentences with a variety of syntactic structures and required to match the sentence to a picture. In the first experiment, subjects matched the spoken sentence to one of two pictures that appeared either before or immediately following the presentation of the sentence. The target picture depicted the spoken sentence correctly and the foil depicted the reversed thematic roles to those in the sentence (i.e., it was a syntactic foil). The second experiment employed a sentence video-verification task in which subjects were required to determine if the spoken sentence matched a videotaped depiction of the action in the sentence or a syntactic foil. In the third experiment, in different conditions, subjects were required to determine whether the spoken sentence matched a single picture or to choose the picture that matched the sentence from an array of two or three pictures. In this experiment, both lexical and syntactic foils were used. In all tasks, DAT patients were affected by the number of propositions in the presented sentence, but not by the syntactic complexity of the sentence. Control subjects also were unaffected by the syntactic complexity of the sentence; the number-of-proposition effect was present in some experiments in the control population. Comparison of performance across the one-, two-, and three-picture versions of the task showed that the magnitude of the effect of number of propositions increased as the number of pictures in the array increased. In addition, analysis of the data from each of the tasks separately showed that the effect of number of propositions only occurred when subjects were attempting to match the target to a syntactic foil (one-picture version) or to choose between the target and a syntactic foil (two-and three-picture versions). The results support the view that patients with DAT do not have disturbances affecting syntactic processing. In addition, they suggest that the effect of number of propositions arises at a stage of analysis that is partially separate from assigning sentence meaning, such as in holding a representation of the sentence in memory until the pictures can be analyzed and encoded and/or in comparing the results of the picture analysis with a stored representation of the sentence meaning. (C) 1998 Academic Press. C1 McGill Univ, Montreal, PQ, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Waters, GS (reprint author), Boston Univ, Dept Commun Disorders, 635 Commonwealth Ave, Boston, MA 02215 USA. OI Rochon, Elizabeth/0000-0001-5521-0513 FU NIA NIH HHS [AG09661] NR 68 TC 31 Z9 33 U1 2 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAY PY 1998 VL 62 IS 3 BP 361 EP 397 DI 10.1006/brln.1997.1880 PG 37 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA ZP877 UT WOS:000073797600003 PM 9593615 ER PT J AU Kozin, SV Gerweck, LE AF Kozin, SV Gerweck, LE TI Cytotoxicity of weak electrolytes after the adaptation of cells to low pH: role of the transmembrane pH gradient SO BRITISH JOURNAL OF CANCER LA English DT Article DE low pH; cell adaptation; pH gradient; weak electrolytes; cytotoxicity ID EXTRACELLULAR PH; INTRACELLULAR-PH; CYTO-TOXICITY; TUMOR PH; CHLORAMBUCIL; MITOXANTRONE; HYPERTHERMIA; HYPOXIA; GROWTH; DRUGS AB Theory suggests that the transmembrane pH gradient may be a major determinant of the distribution of lipophilic weak electrolytes across the cell membrane. The present study evaluates the extent to which this factor contributes to pH-dependent changes in the cytotoxicity of two such chemotherapeutic drugs: chlorambucil and mitoxantrone. Experiments were performed with two cell types of the same origin but exhibiting different pH gradients at the same extracellular pH (pHe): CHO cells cultured under normal physiological conditions (pH 7.4) and acid-adapted cells obtained by culturing under low pH conditions (6.8). Over the pHe range examined (6.0-7.6), the difference between intracellular pH (pHi) and pHe increased with decreasing pHe, Acid-adapted cells were more resistant to acute changes in pHi than normal cells, resulting in substantially larger gradients in these cells. Drug cell survival curves were performed at pHe values of 6.4, 6.8 and 7.4, The cytotoxicity of chlorambucil, a weak acid, increased with decreasing pHe, and low pH-adapted cells were more sensitive than normal cells at the same pHe. In contrast, for the weak base, mitoxantrone, cytotoxicity increased with pHe and was more pronounced in normal cells. As predicted by the theory, the cytotoxicity of both drugs changed exponentially as a function of the pH gradient, regardless of cell type. For mitoxantrone, the rate of such change in cytotoxicity with the gradient was approximately two limes greater than for chlorambucil. This difference is probably due to the presence of two equally ionizable crucial groups on mitoxantrone vs one group on chlorambucil. It is concluded that the cellular pH gradient plays a major role in the pH-dependent modulation of cytotoxicity in these weak electrolytes. The data obtained also suggest that a pronounced differential cytotoxicity may be expected in vivo in tumour vs normal tissue, in comparison with normal cells at a pHe of 7.4 (a model of cells in normal tissues), acid-adapted cells at a pHe of 6.8 (a model of cells distal from supplying blood vessels in tumours) were more sensitive to chlorambucil, with a dose-modifying factor of approximately 6, and were more resistant to mitoxantrone by a factor of 14. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. RP Gerweck, LE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. FU NCI NIH HHS [CA22860] NR 24 TC 19 Z9 19 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1998 VL 77 IS 10 BP 1580 EP 1585 DI 10.1038/bjc.1998.260 PG 6 WC Oncology SC Oncology GA ZQ415 UT WOS:000073858900007 PM 9635832 ER PT J AU Macones, GA Bader, TJ Asch, DA AF Macones, GA Bader, TJ Asch, DA TI Optimising maternal-fetal outcomes in preterm labour: a decision analysis SO BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article ID BETA-MIMETIC AGENT; PREMATURE LABOR; MAGNESIUM-SULFATE; RITODRINE HYDROCHLORIDE; AMNIOTIC-FLUID; BIRTH-WEIGHT; EXPECTANT MANAGEMENT; INTACT MEMBRANES; RANDOMIZED TRIAL; GESTATIONAL-AGE AB Objective To compare, using decision analytic techniques, maternal and fetal risk and benefits of three strategies for the management of preterm labour after 32 weeks. These strategies are empiric tocolysis, no tocolysis, or amniocentesis for fetal maturity testing. Data Sources Published medical literature provided the probabilities, including those for tocolysis efficacy, maternal and neonatal outcomes, and, steroid efficacy. Data Synthesis Separate decision trees were created for hypothetical cohorts of patients presenting with preterm labour at 32, 34, and 36 weeks of gestation to compare strategies. The primary outcome was the total number of expected adverse maternal and neonatal events for each strategy at each gestational age. Results At 32 weeks tocolysis yielded the lowest total number of adverse maternal and neonatal events. At 34 weeks, both tocolysis and no tocolysis yielded similar overall outcomes. At 36 weeks most clinical outcomes were good regardless of strategy. Conclusions This analysis supports the empiric use of tocolytics at 32 weeks. At 34 weeks, either tocolysis or no tocolysis appear to be reasonable alternatives. At 36 weeks no tocolysis is probably preferred. This analysis also suggests that amniocentesis should not be employed in the management of preterm labour at these gestational ages. C1 Univ Penn, Sch Med, Dept Obstet & Gynaecol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. RP Macones, GA (reprint author), Ctr Clin Epidemiol & Biostat, 901 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 52 TC 21 Z9 22 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0306-5456 J9 BRIT J OBSTET GYNAEC JI Br. J. Obstet. Gynaecol. PD MAY PY 1998 VL 105 IS 5 BP 541 EP 550 DI 10.1111/j.1471-0528.1998.tb10156.x PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ZV636 UT WOS:000074325700013 PM 9637125 ER PT J AU Mukai, H Fitzgibbon, WR Ploth, DW Margolius, HS AF Mukai, H Fitzgibbon, WR Ploth, DW Margolius, HS TI Effect of chronic bradykinin B-2 receptor blockade on blood pressure of conscious Dahl salt-resistant rats SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE anaesthesia; blood pressure; bradykinin; Hoe 140; kinin antagonist; renal function; salt resistance ID RENAL-FUNCTION; ANGIOTENSIN-II; HEMODYNAMIC-RESPONSE; ANTAGONIST; HYPERTENSION; KALLIKREIN; HOE-140; KININS; SODIUM; KIDNEY AB 1 In this study 3 protocols were utilized to determine the role of endogenous kinins in the resistance of the inbred Dahl (Rapp) salt-resistant (SR/Jr) rats to high salt diet-induced blood pressure elevation. 2 The bradykinin B-2 receptor antagonist, Hoe 140 (D-Arg[Hyp(3), Thi(5), D-Tic(5), Oic(8)]-bradykinin) at doses of either 10-20 or 20-40 nmol day(-1) (subcutaneously (s.c), via osmotic minipumps, for either 1 or 3 weeks during a high (8%) salt diet) effectively blocked or attenuated the hypotensive responses to 100-1000 ng of bradykinin. 3 In the first protocol, 5 week old SR/Jr rats treated with Hoe 140 (10-20 nmol day(-1), n = 9, s.c., via osmotic minipumps) for 3 weeks and concomitantly fed high (8%) NaCl diet had significantly higher conscious tail cuff blood pressures (BPc) at 1 and 3 weeks when compared with rats treated with vehicle (0.9% NaCl, n = 6). The differences in BPc between the 2 groups were 13 mmHg (P < 0.001) after 1 week and 8 mmHg (P < 0.05) after 3 weeks of treatment. 4 In the second protocol, 5 week old SR/Jr rats were treated with Hoe 140 (20-40 nmol day(-1), n = 8, s.c., via osmotic minipumps) or vehicle (n = 8) for 3 weeks. During the first week of treatment the rats were fed normal (0.8%) NaCl diet. The rats were then switched to 8% NaCl for 2 remaining weeks of the protocol. The mean BPc of Hoe 140-treated rats was not significantly different from that of the vehicle-treated rats when fed 0.8% NaCl diet. In contrast, rats treated with Hoe 140 and concomitantly fed high (8%) NaCl diet had significantly increased BPc (123 +/- 2 vs 111 +/- 1 mmHg, P < 0.001 for the Hoe 140- and vehicle-treated rats, respectively). 5 In the third protocol, treatment with Hoe 140 (20-40 nmol day(-1), s.c., via osmotic minipumps) during high salt diet did not increase BPc in rats that were pre-exposed to the high salt diet for 2 weeks. 6 At the end of 3 weeks of study, blood pressure was measured via an arterial catheter during pentobarbitone-induced anaesthesia. Rats treated with Hoe 140 for 1 or 3 weeks had significantly lower mean arterial blood pressures than the vehicle-treated rats. 7 Our findings suggest that in SR/Jr rats, kinin activation of bradykinin B receptors at least partially contributes to early regulatory mechanisms that resist an increase in blood pressure following exposure to a high salt diet. The mechanism underlying the decreased blood pressure during pentobarbitone anaesthesia of SR/Jr rats chronically treated with Hoe 140 has yet to be elucidated. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Cell & Mol Pharmacol & Expt Therapeut, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Fitzgibbon, WR (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL-44671, HL-17705] NR 37 TC 13 Z9 13 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAY PY 1998 VL 124 IS 1 BP 197 EP 205 DI 10.1038/sj.bjp.0701797 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZM365 UT WOS:000073531200026 PM 9630360 ER PT J AU Marks, IM Baer, L Greist, JH Park, JM Bachofen, M Nakagawa, A Wenzel, KW Parkin, JR Manzo, PA Dottl, SL Mantle, JM AF Marks, IM Baer, L Greist, JH Park, JM Bachofen, M Nakagawa, A Wenzel, KW Parkin, JR Manzo, PA Dottl, SL Mantle, JM TI Home self-assessment of obsessive-compulsive disorder - Use of a manual and a computer-conducted telephone interview: two UK-US studies SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID ANXIETY DISORDERS; DEPRESSION; EXPOSURE AB Background Two studies tested whether subjects with obsessive compulsive disorder could successfully use BT STEPS, a computer-aided system. to perform self-assessment for seif treatment of obsessive-compulsive disorder by exposure and ritual prevention. Method Subjects were given a self-guiding manual and could use a touch-tone telephone to access computer-controlled Interactive Voice Response interviews at their convenience from home. Using the BT STEPS system, patients rated themselves and worked out a plan for individually tailored self-exposure therapy. Results Outcomes were similar in the two studies. Of the 63 subjects who used BT STEPS, 84% completed the self-assessment module. Most calls were made outside usual office hours. As expected, subjects did not improve merely by completing self-assessment. However, completion of self-assessment predicted later improvement with self-exposure therapy. Conclusions Most subjects successfully completed self-assessment using BT STEPS from their homes. Declaration of interest BT STEPS is a trademark of Pfizer, Inc. I.M.M., L.B. and J.H.G. have a financial interest in BT STEPS. C1 Inst Psychiat, London SE5 8AF, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dean Fdn Hlth Res & Educ, Middleton, WI USA. RP Marks, IM (reprint author), Inst Psychiat, London SE5 8AF, England. NR 18 TC 52 Z9 52 U1 3 U2 5 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAY PY 1998 VL 172 BP 406 EP 412 DI 10.1192/bjp.172.5.406 PG 7 WC Psychiatry SC Psychiatry GA ZN110 UT WOS:000073610900009 PM 9747402 ER PT J AU Berdud, I Martin-Malo, A Almaden, Y Aljama, P Rodriguez, M Felsenfeld, AJ AF Berdud, I Martin-Malo, A Almaden, Y Aljama, P Rodriguez, M Felsenfeld, AJ TI The PTH-calcium relationship during a range of infused PTH doses in the parathyroidectomized rat SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE calcium; hypoparathyroidism; hyperparathyroidism; parathyroid hormone; phosphorus ID PRIMARY HYPERPARATHYROIDISM; CALCEMIC RESPONSE; RENAL-FAILURE; HORMONE; PHOSPHORUS; CALCITRIOL; WEIGHT; BASAL AB To establish the PTH dosage that maintains normal mineral homeostasis in the PTX rat, a series of doses of rat 1-34 PTH were infused via a subcutaneously implanted miniosmotic pump. The doses were 0, 0.011, 0.022, 0.044, and 0.11 mu g/100 g/hour. After 48 hours, serum calcium ranged from 5.56 +/- 0.02 to 16.29 +/- 0.25 mg/dl, ANOVA P < 0.001, and serum phosphorus from 12.49 +/- 0.03 to 5.33 +/- 0.34 mg/dl, ANOVA P < 0.001. By post hoc test, the serum calcium level was different (P < 0.05) at every PTH dose; the serum phosphorus level was different (P < 0.05) at every PTH dose except between the two highest doses. The PTH dosage that produced a normal serum calcium (10.09 +/- 0.10 mg/dl) and phosphorus (6.90 +/- 0.18 mg/dl) was 0.022 mu g/ 100 g/hour. The relationship between increasing doses of PTH and both serum calcium and phosphorus was curvilinear and the calcium-phosphorus product was remarkably constant from a serum calcium of 7-13 mg/dl. The increase in serum calcium and the decrease in serum phosphorus were more rapid at lower than at higher PTH doses so that for both, an asymptote was reached. At the highest serum calcium values, the calcium-phosphorus product increased and in individual rats, an increase in serum phosphorus was associated with a decrease in serum calcium. Ln summary, this study shows that (1) for rat 1-34 PTH, the normal replacement dose in the PTX rat with normal renal function on a normal diet is 0.022 mu/100 g/hour; (2) the relationship between PTH and both serum calcium and phosphorus is curvilinear, and an asymptote is reached for both; and (3) the calcium-phosphorus product is remarkably constant as the serum calcium increases from 7 to 13 mg/dl and only increased during marked hypercalcemia when serum phosphorus did not decrease further or even tended to increase. C1 Hosp Univ Reine Sofia, Dept Nephrol, Cordoba, Spain. Hosp Univ Reine Sofia, Unit Invest, Cordoba, Spain. W Los Angeles Vet Adm Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Rodriguez, M (reprint author), Hosp Univ Reine Sofia, Dept Nephrol, Cordoba, Spain. RI Rodriguez, teresa/H-5452-2011 NR 38 TC 20 Z9 21 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD MAY PY 1998 VL 62 IS 5 BP 457 EP 461 DI 10.1007/s002239900460 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZG607 UT WOS:000073020700013 PM 9541525 ER PT J AU Herbst, RS Takeuchi, H Teicher, BA AF Herbst, RS Takeuchi, H Teicher, BA TI Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE TNP-470; Antiangiogenic agents; TNP-470/minocycline ID ANGIOGENESIS INHIBITOR TNP-470; CYTOTOXIC CANCER THERAPIES; TUMOR-GROWTH; AGM-1470; MINOCYCLINE; INVIVO; AGENTS; POTENTIATION; COMBINATION; FUMAGILLIN AB Introduction: With the introduction of new drugs, the efficacy of chemotherapy in non-small-cell lung cancer has been improving. The combination of paclitaxel and carboplatin has shown activity in this disease but is far from curative, Methods: The antiangiogenic agent regimen of TNP-470/minocycline was added to treatment with paclitaxel and carboplatin alone and in combination in animals bearing the Lewis lung carcinoma. Results: Administration of the antiangiogenic regimen prior to, during and after the cytotoxic therapy increased the tumor growth delay 1.6-fold and decreased the number of lung metastases to 20% of the number observed in the control animals. [C-14]Paclitaxel, platinum from carboplatin and [C-14]albumin levels were determined over a 24-h time course in tumors and normal tissues of animals bearing the Lewis lung carcinoma and pretreated with TNP-470/minocycline or not pretreated. There were higher levels of [C-14]paclitaxel, platinum from carboplatin and [C-14]albumin in the tumors and some normal tissues of the animals that had received TNP-470/minocycline compared with those that had not received TNP-470/minocycline, especially at the earlier time points. Administration of TNP-470/ minocycline to animals bearing the EMT-6 mammary carcinoma increased the cytotoxicity of high-dose paclitaxel toward EMT-6 tumor cells and toward bone marrow CFU-GM. Administration of TNP-470/minocycline to animals bearing the EMT-6 mammary carcinoma also increased the cytotoxicity of carboplatin toward the EMT-6 tumor cells but did not affect the toxicity of carboplatin toward the bone marrow CFU-GM. Conclusions: The addition of TNP-470/minocycline to treatment with paclitaxel and carboplatin resulted in increased antitumor activity and efficacy and further investigation of this combination is warranted. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Teicher, BA (reprint author), Lilly Corp Ctr, Lilly Res Labs, DC 0540, Indianapolis, IN 46285 USA. NR 38 TC 46 Z9 48 U1 1 U2 4 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 MAY PY 1998 VL 41 IS 6 BP 497 EP 504 DI 10.1007/s002800050773 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA ZJ025 UT WOS:000073172000011 PM 9554595 ER PT J AU Platz, EA Giovannucci, E Dahl, DM Krithivas, K Hennekens, CH Brown, M Stampfer, MJ Kantoff, PW AF Platz, EA Giovannucci, E Dahl, DM Krithivas, K Hennekens, CH Brown, M Stampfer, MJ Kantoff, PW TI The androgen receptor gene GGN microsatellite and prostate cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID N-TERMINAL DOMAIN; CARCINOMA; CAG AB The androgen receptor (AR) gene contains a polymorphic GGN microsatellite in exon 1, which encodes polyglycine in the amino terminus of the AR. Previous work has shown that a polymorphic region of CAG repeats also in exon 1 is inversely related to the ability of the AR to transactivate other genes and to prostate cancer risk. We investigated whether AR gene GGN repeat length is related to prostate cancer in a nested study of 582 cases and 794 controls matched on age and smoking status in the Physicians' Health Study. DNA was prepared from archived blood. Using PCR, the region surrounding the GGN repeat was amplified. Fluorescence-labeled primers were used such that the fragment produced could be sized using polyacrylamide gels and Genescan software. We estimated odds ratios and 95% confidence intervals from logistic models controlling for the matching variables for the relation between GGN repeat length and total prostate cancer and by stage/grade and by age at diagnosis. Among controls, the most frequent GGN repeat lengths were 23 (53.5%) and 24 (34.0%), with a range of 10-29, There was no statistically significant difference in the mean GGN repeat length between cases (23.13) and controls (23.05), However, cases had a narrower spread of repeats lengths (parametric test, P = 0.03; nonparametric test, P = 0.07) than controls, with fewer extreme lengths in either direction. The risk of total prostate cancer was slightly increased for a GGN repeat length of 23 compared to all others (odds ratio, 1.20; 95% confidence interval 0.97-1.49); risk did not vary by tumor stage/grade. For every one repeat deviation in either direction from 23, the risk of prostate cancer decreased by 8% (P = 0.04), Although the AR gene GGN repeat probably plays only a modest role in prostate cancer, the observed relation of this repeat with prostate cancer risk supports the evaluation of the effect of GGN repeat length on AR transactivation. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Div Urol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Neoplast Dis Mechanisms, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Giovannucci, E (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA-42182]; NHLBI NIH HHS [HL-26490, HL-34595] NR 16 TC 74 Z9 76 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1998 VL 7 IS 5 BP 379 EP 384 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZM687 UT WOS:000073565800004 PM 9610786 ER PT J AU Rainov, NG Dobberstein, KU Heidecke, V Dorant, U Chase, M Kramm, CM Chiocca, EA Breakefield, XO AF Rainov, NG Dobberstein, KU Heidecke, V Dorant, U Chase, M Kramm, CM Chiocca, EA Breakefield, XO TI Long-term survival in a rodent brain tumor model by bradykinin-enhanced intra-arterial delivery of a therapeutic herpes simplex virus vector SO CANCER GENE THERAPY LA English DT Article DE brain neoplasms; gene therapy; herpes simplex virus type 7; intra-arterial application; thymidine kinase ID CENTRAL-NERVOUS-SYSTEM; THYMIDINE KINASE GENE; BARRIER DISRUPTION; GANCICLOVIR; NEOPLASMS; CELLS; TRANSDUCTION; ADENOVIRUS AB Recently, it was demonstrated that bradykinin (BK) enhances intracarotid delivery of herpes simplex virus type I (HSV) vectors to rat brain tumors, and that gene transfer lakes place predominantly in the tumor periphery. The aim of the present study was to apply these findings to the treatment of experimental rat brain tumors. The HSV mutant, hrR3, which is disrupted in the ribonucleotide reductase gene, was injected intra-arterially with titers of 1 X 10(8), 1 X 10(9), and 1 X 10(10) plaque-forming units (pfu) both with and without BK into Fischer 344 rats with intracerebral, syngeneic 9L tumors. Starting on day 3 after vector administration, animals were treated by intraperitoneal injection of 60 mg/kg/day ganciclovir (GCV) or placebo. 1 X 10(10) pfu hrR3 in combination with BK and GCV treatment was able to eradicate tumors in 80% of the animals; 1 X 10(9) pfu cured 40% of the rats, and 1 X 10(8) pfu achieved an extension of survival time but no tumor cures. Control groups had 100% mortality within 30 days after injection of tumor cells, with the exception of the group with injection of 1 X 10(10) pfu of virus and GCV treatment, which had one long-term survivor. No apparent complications of this novel type of brain tumor gene therapy were encountered. In conclusion, intra-arterial injection of attenuated HSV vectors with blood-tumor barrier modification and subsequent systemic GCV application appears to be a promising approach for the treatment of malignant brain tumors. C1 Univ Halle Wittenberg, Fac Med, Dept Neurosurg, Halle, Germany. Massachusetts Gen Hosp East, Ctr Neurosci, Mol Neurogenet Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Mol Neuroobcol Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA. Univ Dusseldorf, Fac Med, Dept Pediat, D-4000 Dusseldorf, Germany. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Ctr Neurosci, 13th St,Bldg 149, Charlestown, MA 02129 USA. NR 24 TC 20 Z9 21 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAY-JUN PY 1998 VL 5 IS 3 BP 158 EP 162 PG 5 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA ZP536 UT WOS:000073763300004 PM 9622099 ER PT J AU Jain, RK AF Jain, RK TI Integrative pathophysiology of solid tumors: Role in detection and treatment SO CANCER JOURNAL LA English DT Article; Proceedings Paper CT Oncology Frontiers Conference CY OCT 15-19, 1997 CL CAYMAN ISLAND SP Hoechst Marion Roussel, Kansas City ID INTERSTITIAL FLUID PRESSURE; ENDOTHELIAL GROWTH-FACTOR; NATURAL-KILLER-CELLS; VASCULAR-PERMEABILITY FACTOR; COLON ADENOCARCINOMA XENOGRAFT; POSITRON EMISSION TOMOGRAPHY; ENZYME-CONJUGATED ANTIBODIES; INDUCED LEUKOCYTE ADHESION; BLOOD-FLOW; MICROVASCULAR PERMEABILITY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. NR 151 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD MAY PY 1998 VL 4 SU 1 BP S48 EP S57 PG 10 WC Oncology SC Oncology GA ZQ074 UT WOS:000073818800009 PM 9619271 ER PT J AU Nelson, HH Wiencke, JK Gunn, L Wain, JC Christiani, DC Kelsey, KT AF Nelson, HH Wiencke, JK Gunn, L Wain, JC Christiani, DC Kelsey, KT TI Chromosome 3p14 alterations in lung cancer: Evidence that FHIT exon deletion is a target of tobacco carcinogens and asbestos SO CANCER RESEARCH LA English DT Article ID CELL-LINES; GENE; ABNORMALITIES; MUTATIONS; HEAD; P53 AB Alterations in the FRIT gene region have been previously associated with smoking status and the occurrence of lung tumors. In the current study, we examined the nature of the mutations that occur at FHIT and the types of carcinogen exposures that are associated with FHIT alterations. We screened 40 primary lung tumors for the presence of point mutations within the coding exons of FHIT using PCR-single-strand conformational polymorphism. Tumors were also analyzed for allelic loss using microsatellite markers located in or near FRIT. No tumors contained point mutations within the coding region of the FHIT gene. However, several samples failed to generate a PCR product, suggesting that regions of the gene are homozygously deleted. Samples were reanalyzed for exon loss using PCR; 13 of 30 tumors failed to generate a PCR product, and 20 of 30 tumors were missing at least one FHIT exon or had loss (loss of heterozygosity or deletion) of one microsatellite markers suggesting that regions of the gene are homozygously deleted. These data indicate that the FHIT gene has a novel pattern of mutational inactivation not seen previously with other tumor suppressor genes, most likely influenced by the proximity of the FRA3B region. There were no associations of age, sex, p53, or k-ras mutation and FHIT exon deletion. However, there if as an association of smoking duration and asbestos exposure with FHIT exon loss, indicating that carcinogenic exposures may be causal in the generation of alterations in the FHIT region. C1 Harvard Univ, Sch Med, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Lab Mol Epidemiol, San Francisco, CA 94143 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pulm & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thorac Surg Unit, Boston, MA 02114 USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Med, Sch Publ Hlth, Dept Canc Cell Biol, 665 Huntington Ave, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014 FU NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES/CA06409, ES00002] NR 25 TC 95 Z9 102 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1998 VL 58 IS 9 BP 1804 EP 1807 PG 4 WC Oncology SC Oncology GA ZK631 UT WOS:000073344700008 PM 9581816 ER PT J AU Cheng, LL Chang, IW Louis, DN Gonzalez, RG AF Cheng, LL Chang, IW Louis, DN Gonzalez, RG TI Correlation of high-resolution magic angle spinning proton magnetic resonance spectroscopy with histopathology of intact human brain tumor specimens SO CANCER RESEARCH LA English DT Article ID HUMAN THYROID NEOPLASIA; IN-VITRO; H-1-NMR SPECTROSCOPY; MR SPECTROSCOPY; H-1 MRS; LYMPH-NODES; VIVO; METABOLITE; CANCER; DIFFERENTIATION AB High-resolution magic angle spinning proton (HRMAS H-1) magnetic resonance spectroscopy produces well-resolved spectra of metabolites from intact tissue specimens. Here we report the results of a preliminary study of 19 human brain tumors obtained by applying this method. Among these 19 cases were 2 low-grade astrocytomas, 1 anaplastic astrocytoma, 8 glioblastomas, 6 meningiomas, and 2 schwannomas. In addition, autopsy human brain tissues from two subjects without any known neurological diseases were used as normal controls. The HRMAS H-1 magnetic resonance spectroscopy measurements were performed at 2 degrees C on a 400-MHz NMR spectrometer with a HRMAS speed of 2.5 kHz. From these HRMAS H-1 MR spectra, we measured the concentrations of 11 metabolites, the ratios of 15 metabolites (resonances) to creatine (at 3.03 ppm), and the spin-spin relaxation time for these metabolites (resonances). Our results indicate that these parameters have the potential to characterize tumor types and grades with statistical significance as well as identify tumor biochemical characteristics. In particular, we found that compared with metabolite concentrations and metabolite spin-spin relaxation time, the metabolic ratios presented the highest sensitivity in differentiating normal tissue from tumors, as well as in distinguishing between tumor groups. Of 15 analyzed metabolic ratios, 12 showed statistical significance in differentiating normal tissue from low-grade and anaplastic astrocytomas, 13 showed statistical significance in differentiating normal tissue from glioblastomas, 14 showed statistical significance in differentiating normal tissue from schwannomas, and 9 showed statistical significance in differentiating normal tissue from meningiomas. Moreover, our results strongly indicate that the resonance ratio of inositol (at 4.05 ppm) to creatine may help distinguish tumor type. Our results suggest that the HRMAS method for intact tissue measurement may function as an adjunct to histopathology and contribute to improved accuracy for brain tumor diagnoses. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02129 USA. RP Cheng, LL (reprint author), Massachusetts Gen Hosp CNY7, 149 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS24279, NS34626] NR 44 TC 155 Z9 168 U1 0 U2 12 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1998 VL 58 IS 9 BP 1825 EP 1832 PG 8 WC Oncology SC Oncology GA ZK631 UT WOS:000073344700012 PM 9581820 ER PT J AU Zhang, J Kashket, S AF Zhang, J Kashket, S TI Inhibition of salivary amylase by black and green teas and their effects on the intraoral hydrolysis of starch SO CARIES RESEARCH LA English DT Article DE amylase; black tea; cariogenicity; green tea; inhibition; maltose; starch; tannins ID STREPTOCOCCUS-MUTANS; GLUCAN SYNTHESIS; GLUCOSYLTRANSFERASE; POLYPHENOLS; BACTERIUM AB Tea decoctions prepared from a number of black and green teas inhibited amylase in human saliva. Black teas gave higher levels of inhibition than green teas, and removal of tea tannins with gelatin led to the loss of inhibitory activity from all decoctions. Streptococcal amylase was similarly inhibited by tea decoctions. Fluoride was without effect on amylase. Since salivary amylase hydrolyzes food starch to low molecular weight fermentable carbohydrates, experiments were carried out to determine whether tea decoctions would interfere with the release of maltose in food particles that became entrapped on the dentition. Subjects consumed salted crackers and rinsed subsequently for 30 s with black or green tea decoctions, or water. Maltose release was reduced by up to about 70% after rinsing with the teas. Black tea decoction was significantly more effective than green tea, in agreement with the in vitro data. The observations supported the hypothesis that tea consumption can be effective in reducing the cariogenic potential of starch-containing foods such as crackers and cakes. Tea may reduce the tendency for these foods to serve as slow-release sources of fermentable carbohydrate. C1 Forsyth Dent Ctr, Nutr Sect, Boston, MA 02115 USA. Forsyth Dent Ctr, Ctr Res Oral & Biol Effects Foods, Boston, MA 02115 USA. RP Kashket, S (reprint author), Forsyth Dent Ctr, Nutr Sect, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-05253] NR 35 TC 80 Z9 84 U1 2 U2 28 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PD MAY-JUN PY 1998 VL 32 IS 3 BP 233 EP 238 DI 10.1159/000016458 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZG283 UT WOS:000072985500012 PM 9577990 ER PT J AU Yao, TP Oh, SP Fuchs, M Zhou, ND Ch'ng, LE Newsome, D Bronson, RT Li, E Livingston, DM Eckner, R AF Yao, TP Oh, SP Fuchs, M Zhou, ND Ch'ng, LE Newsome, D Bronson, RT Li, E Livingston, DM Eckner, R TI Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300 SO CELL LA English DT Article ID CREB-BINDING-PROTEIN; COACTIVATOR CBP; BHLH PROTEINS; NEURAL-TUBE; COMPLEX; ACETYLTRANSFERASE; SUPPRESSOR; ACTIVATION; EXPRESSION; LETHALITY AB The transcriptional coactivator and integrator p300 and its closely related family member CBP mediate multiple, signal-dependent transcriptional events. We have generated mice lacking a functional p300 gene. Animals nullizygous for p300 died between days 9 and 11.5 of gestation, exhibiting defects in neurulation, cell proliferation, and heart development. Cells derived from p300-deficient embryos displayed specific transcriptional defects and proliferated poorly. Surprisingly, p300 heterozygotes also manifested considerable embryonic lethality. Moreover, double heterozygosity for p300 and cbp was invariably associated with embryonic death. Thus, mouse development is exquisitely sensitive to the overall gene dosage of p300 and cbp. Our results provide genetic evidence that a coactivator endowed with histone acetyltransferase activity is essential for mammalian cell proliferation and development. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Tufts Univ, Sch Vet Med, Boston, MA 02111 USA. Univ Zurich, Inst Mol Biol, CH-8057 Zurich, Switzerland. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 55 TC 652 Z9 666 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAY 1 PY 1998 VL 93 IS 3 BP 361 EP 372 DI 10.1016/S0092-8674(00)81165-4 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZL787 UT WOS:000073471500012 PM 9590171 ER PT J AU Takahashi, K Donovan, MJ Rogers, RA Ezekowitz, RAB AF Takahashi, K Donovan, MJ Rogers, RA Ezekowitz, RAB TI Distribution of murine mannose receptor expression from early embryogenesis through to adulthood SO CELL AND TISSUE RESEARCH LA English DT Article DE mannose receptor; macrophage-specific antigen F4/80; macrophages; endothelial cells embryogenesis; development; immunohistochemistry; mouse (C57Black/6, BALB/c) ID RAT-LIVER CELLS; ACTIVATED MOUSE MACROPHAGES; ENDOTHELIAL-CELLS; DOWN-REGULATION; PLASMINOGEN-ACTIVATOR; MEDIATED ENDOCYTOSIS; COMPLEMENT RECEPTORS; PARENCHYMAL-CELLS; INTERFERON-GAMMA; DENDRITIC CELLS AB The mannose receptor is a 175-kDa transmembrane glycoprotein that appears to be expressed on the surface of terminally differentiated macrophages and Langerhans. cells. The ectodomain of the mannose receptor has eight carbohydrate recognition domains. The receptor recognizes the patterns of sugars that adorn a wide array of bacteria, parasites, yeast, fungi, and mannosylated ligands. Clearance studies in whole animals have localized radiolabeled ligands, such as mannosylated bovine serum albumen, not only to macrophages, but also to liver sinusoidal endothelial cells. Hitherto, there has been no comprehensive analysis of expression of the mannose receptor in embryonic and adult mouse tissues. In this study, we have undertaken a systematic survey of the expression of the mannose receptor from early embryogenesis through to adulthood. The mannose receptor is expressed on tissue macrophages throughout the adult mouse as expected. However, the mannose receptor is first observed on embryonic day 9 on cells that line blood island vessel walls in the yolk sac. The mannose receptor is localized on sinusoidal endothelial cells in embryonic liver by embryonic day 11 and in bone marrow at embryonic day 17. This pattern persists in these organs throughout embryogenesis into adulthood when sinusoidal endothelial cells of lymph nodes also express the mannose receptor. The receptor is also found on lymphatic endothelial cells of small intestine. In contrast, sinusoids of spleen and thymus do not express mannose receptor antigen. This study demonstrates that the mannose receptor is expressed on tissue macrophages and on subsets of vascular and lymphatic endothelial cells. Thus, the mannose receptor maybe a marker of the so-called reticuloendothelial system. C1 Massachusetts Gen Hosp, Dept Pediat, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Takahashi, K (reprint author), Massachusetts Gen Hosp, Dept Pediat, Lab Dev Immunol, Jackson 14,Blossom St, Boston, MA 02114 USA. EM Takahashik@A1.mgh.harvard.edu FU NHLBI NIH HHS [HL-43510] NR 45 TC 62 Z9 62 U1 0 U2 10 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD MAY PY 1998 VL 292 IS 2 BP 311 EP 323 DI 10.1007/s004410051062 PG 13 WC Cell Biology SC Cell Biology GA ZQ431 UT WOS:000073860900014 PM 9560474 ER PT J AU Glowacki, J Mizuno, S Greenberger, JS AF Glowacki, J Mizuno, S Greenberger, JS TI Perfusion enhances functions of bone marrow stromal cells in three-dimensional culture SO CELL TRANSPLANTATION LA English DT Article DE bone marrow stromal cells; in vitro; perfusion; three-dimensional ID COLONY-STIMULATING FACTOR; HUMAN DERMAL FIBROBLASTS; INDUCED OSTEOGENESIS; DEMINERALIZED BONE; PROGENITOR CELLS; HEPARAN-SULFATE; IN-VITRO; CHONDROINDUCTION; DIFFERENTIATION; PROTEOGLYCANS AB Perfusion of medium through three-dimensional (3D) collagen sponges enhanced viability and function of cocultivated marrow stromal and hematopoietic cell lines, Cells of the murine bone marrow stromal cell line GPIa were cultured in novel 3D collagen sponges, made from pepsin-digested bovine skin, Static cultures of sponges mere maintained in dishes with media changes every other day. Perfused sponges were contained in a glass column with medium flow set at 1.3 mL/min. In some sponges, the 32D cl3 c-fms(m) (CRX-1) hematopoietic progenitor cell line was added 7 days after GPIa cells. At 7 and 16 days, light microscopic evaluation showed poor viability of cells in static sponge cultures. In perfused sponge cultures, there was greater cellularity throughout the sponge and abundant accumulation of metachromatic extracellular matrix surrounding GPIa cells. Chondroitin 6-sulfate and heparan sulfate were identified as components of the matrix by immunohistochemical methods. DNA synthesis was evaluated by 15-h exposure of cultures to bromodeoxyuridine (BrdU), with subsequent immunohistochemical localization with monoclonal anti-BrdU antibody. Cells positive for BrdU were identified at the outer surfaces of both static and perfused sponges; however, positive cells were also seen throughout the internal areas of the sponges that were perfused. These results suggest that better nutrient exchange occurred in perfused sponges, In static cocultures of GPIa and CRX-1 cells, there was no detectable viability of the IL-3-dependent CRX-1 cells; however, under perfused conditions, CRX-1 cells flourished within the sponges as documented by BrdU incorporation. Thus, medium perfusion enhanced GPIa stromal cell line viability and function in 3D collagen sponge cultures, as demonstrated by BrdU incorporation, matrix production, and support of CRX-1 cells. This novel culture system may be useful for examining the interactions of bone marrow stromal cells with extracellular matrix molecules, soluble and matrix-bound factors, and with other cell types. (C) 1998 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Skeletal Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Dept Radiat Oncol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. RP Glowacki, J (reprint author), Massachusetts Gen Hosp, Skeletal Biol Res Ctr, MGH CNY 5031,13th St, Charlestown, MA 02129 USA. FU NIDCR NIH HHS [DE08798] NR 31 TC 109 Z9 120 U1 1 U2 11 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD MAY-JUN PY 1998 VL 7 IS 3 BP 319 EP 326 DI 10.1016/S0963-6897(98)00003-7 PG 8 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA ZU508 UT WOS:000074205100010 PM 9647441 ER PT J AU Byrd, JC Lawrence, D Arthur, DC Pettenati, MJ Tantravahi, R Qumsiyeh, M Stamberg, J Davey, FR Schiffer, CA Bloomfield, CD AF Byrd, JC Lawrence, D Arthur, DC Pettenati, MJ Tantravahi, R Qumsiyeh, M Stamberg, J Davey, FR Schiffer, CA Bloomfield, CD TI Patients with isolated trisomy 8 in acute myeloid leukemia are not cured with cytarabine-based chemotherapy: Results from cancer and leukemia group B 8461 SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; PROGNOSTIC-SIGNIFICANCE; CLASSIFICATION; ABNORMALITIES; KARYOTYPE; THERAPY; IMPACT; ADULTS AB To date, neither the clinical significance of isolated trisomy 8, the most frequent trisomy in acute myeloid leukemia (AML), nor the effect of age within a single cytogenetic group has been examined. We report a large cohort of adult trisomy 8 patients and examine whether increasing age within a homogeneous cytogenetic group alters clinical outcome. Characteristics and outcome of patients with isolated trisomy 8 enrolled in the prospective Cancer and Leukemia Group B (CALGB) cytogenetic study CALGB 8461 are described. Isolated trisomy 8 was identified in 42 (3.03%) of 1387 patients enrolled in five CALGB treatment protocols. These patients had a median age of 64 (range, 16-79) years, 50% female proportion, and a low frequency of hepatomegaly (10%) or splenomegaly (10%), Laboratory features included a median white blood count of 7.3 x 10(9)/L, nonspecific French-American-British distribution, with 36% of patients having Auer rods. Treatment outcome was unsatisfactory with a complete remission (CR) rate of 59%, median CR duration of 13.6 months, and median survival of 13.1 months, Older age adversely affected outcome; trisomy 8 patients greater than or equal to 60 years had both an inferior CR rate (40% versus 88%; P = 0.004) and overall survival (median, 4.8 versus 17.5 months; P = 0.01), as compared with those <60 years of age. Of the patients <60 years of age, only four remain alive, and all received noncytarabine-based intensive chemotherapy, followed in three cases by autologous (n = 2) or allogeneic (n = 1) stem cell transplant in CR1, Adults with AML and isolated trisomy 8 have a poor outcome that is accentuated by increasing age and is rarely cured with cytarabine-based therapy, Alternative investigational treatments should be considered for individuals with this AML subset. C1 Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27157 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. Syracuse Univ, Hlth Sci Ctr, Syracuse, NY 13210 USA. RP Byrd, JC (reprint author), Walter Reed Army Med Ctr, Hematol Oncol Serv, Ward 78, Washington, DC 20307 USA. FU NCI NIH HHS [CA26806]; PHS HHS [26806, 37027] NR 27 TC 31 Z9 31 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 1998 VL 4 IS 5 BP 1235 EP 1241 PG 7 WC Oncology SC Oncology GA ZL982 UT WOS:000073493000019 PM 9607582 ER PT J AU Yamada, K Tohyama, H Shizawa, Y Kohno, M Fukunishi, Y Tomoe, M AF Yamada, K Tohyama, H Shizawa, Y Kohno, M Fukunishi, Y Tomoe, M TI Direct duodenal invasion of hepatocellular carcinoma - Intestinal hemorrhage treated by transcatheter arterial embolization SO CLINICAL IMAGING LA English DT Article DE hepatocellular carcinoma; liver, CT; duodenal neoplasm; TAE AB This report describes a case of direct duodenal invasion of hepatocellular carcinoma with massive intermittent gastrointestinal (GI) bleeding. Progressive anemia tvas intractable by supportive therapy alone, and repeated blood transfusion was necessary. Transcatheter arterial embolization was finally carried out, which dramatically reduced the amount of transfusion. Owing to severe blood loss, patients with GI tract involvement generally have a poor prognosis. (C) Elsevier Science Inc., 1998. C1 St Marianna Univ, Sch Med, Dept Radiol, Miyamae Ku, Kawasaki, Kanagawa, Japan. Sagamihara Kyoudou Hosp, Sagamihara, Kanagawa, Japan. RP Yamada, K (reprint author), Massachusetts Gen Hosp, NMR Ctr, 13th St,Bldg 149 2301,Charlestown Navy Yard, Boston, MA 02129 USA. NR 8 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-7071 J9 CLIN IMAG JI Clin. Imaging PD MAY-JUN PY 1998 VL 22 IS 3 BP 196 EP 199 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZF817 UT WOS:000072936200006 PM 9559232 ER PT J AU Zvejnieks, PA Lichtenstein, KA Koneman, EW AF Zvejnieks, PA Lichtenstein, KA Koneman, EW TI Photo quiz II - Diagnosis: Luminal anisakidosis due to Pseudoterranova decipiens SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Columbia Rose Med Ctr, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Zvejnieks, PA (reprint author), Univ Colorado, Hlth Sci Ctr, B-216,4200 E 9th Ave, Denver, CO 80262 USA. NR 5 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1998 VL 26 IS 5 BP 1085 EP + PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZM239 UT WOS:000073518600011 PM 9597231 ER PT J AU Mascarenas, CA Hardin, TC Pennick, GJ Rinaldi, MG Graybill, JR AF Mascarenas, CA Hardin, TC Pennick, GJ Rinaldi, MG Graybill, JR TI Treatment of thrush with itraconazole solution: Evidence for topical effect SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID FLUCONAZOLE C1 Audie L Murphy Mem Vet Hosp, Infect Dis Sect 111F, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. RP Graybill, JR (reprint author), Audie L Murphy Mem Vet Hosp, Infect Dis Sect 111F, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 6 TC 9 Z9 9 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1998 VL 26 IS 5 BP 1242 EP 1243 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZM239 UT WOS:000073518600051 PM 9597271 ER PT J AU Hwang, JI Chiang, JH Yu, C Cheng, HC Chang, CY Mueller, PR AF Hwang, JI Chiang, JH Yu, C Cheng, HC Chang, CY Mueller, PR TI Pictorial review: Radiological diagnosis of duodenal abnormalities SO CLINICAL RADIOLOGY LA English DT Review ID CT; NEOPLASMS; TUMORS; LOOP; SIGN AB This article depicts the radiological findings of many common gastrointestinal entities, Specifically, examples of disease processes that affect the stomach, gall bladder, small intestine, pancreas and colon are shown. In most cases there is correlation between ultrasound, computed tomography (CT) and fluoroscopic imaging. The major emphasis of the article, however, is to demonstrate classic barium imaging of a large number of gastrointestinal disease processes. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Vet Gen Hosp, Dept Radiol, Taipei, Taiwan. Natl Yang Ming Univ, Dept Radiol, Taipei 112, Taiwan. Harvard Univ, Sch Med, Boston, MA USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 220,32 Fruit St, Boston, MA 02114 USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD MAY PY 1998 VL 53 IS 5 BP 323 EP 332 DI 10.1016/S0009-9260(98)80002-0 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZP535 UT WOS:000073763200002 PM 9630268 ER PT J AU Schima, W Ryan, JM Harisinghani, M Schober, E Pokieser, P Denk, DM Stacher, G AF Schima, W Ryan, JM Harisinghani, M Schober, E Pokieser, P Denk, DM Stacher, G TI Radiographic detection of achalasia: Diagnostic accuracy of videofluoroscopy SO CLINICAL RADIOLOGY LA English DT Article ID ESOPHAGEAL MOTOR DISORDERS; MOTILITY DISORDERS; MANOMETRY; RADIOLOGY; DYSPHAGIA; REFLUX AB Aims: To retrospectively evaluate the accuracy of videofluoroscopy in the diagnosis of achalasia. Materials and Methods: Videofluoroscopic studies of the oesophagus of 53 patients (25 males, 28 females; mean age, 49 years) with manometrically revealed diagnosis of achalasia were retrospectively evaluated. The videofluoroscopic examinations had been carried out with one swallow of low-density barium suspension in the erect and up to three swallows in the prone oblique position. Videofluoroscopically, a diagnosis of achalasia was made in 31 of the patients (58%) with manometrically proven achalasia, of whom only nine had oesophageal dilatation, Non-specific oesophageal motor abnormalities mere diagnosed radiographically in 18 patients (34%) and a normal motility in four patients (8%). Conclusion: Videofluoroscopy is a valuable and sensitive technique for the detection of disordered oesophageal motility in achalasia. C1 Univ Vienna, Dept Radiol, A-1090 Vienna, Austria. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Vienna, Ludwig Boltzmann Inst Radiol Tumour Res, Vienna, Austria. Univ Vienna, Dept Otorhinolaryngol, Vienna, Austria. Univ Vienna, Dept Surg, Psychophysiol Unit, Vienna, Austria. RP Schima, W (reprint author), Univ Vienna, Dept Radiol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. NR 31 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD MAY PY 1998 VL 53 IS 5 BP 372 EP 375 DI 10.1016/S0009-9260(98)80012-3 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZP535 UT WOS:000073763200012 PM 9630278 ER PT J AU Wilens, TE Biederman, J Spencer, TJ AF Wilens, TE Biederman, J Spencer, TJ TI Pharmacotherapy of attention deficit hyperactivity disorder in adults SO CNS DRUGS LA English DT Article ID MINIMAL BRAIN-DYSFUNCTION; RESIDUAL TYPE; OPEN TRIAL; PSYCHIATRIC COMORBIDITY; DOUBLE-BLIND; METHYLPHENIDATE; ADHD; DESIPRAMINE; VENLAFAXINE; DIAGNOSIS AB Attention deficit hyperactivity disorder (ADHD) in adults is an increasingly recognised condition that is associated with substantial functional impairment. Adults with ADHD present with a developmental derivation of symptoms reminiscent of those in juveniles, most notably inattention and distractibility and, less commonly, hyperactivity and impulsivity. Psychiatric comorbidity with mood, anxiety, substance use and antisocial personality disorders are often found in adults with ADHD. As with children with ADHD, the mainstay of treatment in adults with the disorder is pharmacotherapy. In contrast to the vast amount of data available on the treatment of children with ADHD, there have been only a limited number of medication studies in adults with the disorder. Nine studies (n = 245) of psychostimulants and 16 studies (n = 273) of nonstimulant medications, including antidepressants, antihypertensives and amino acids, have been published. A review of the literature indicates that the majority of controlled investigations assessed the effects of psychostimulants, while nonstimulant agents have generally been studied under open conditions. Stimulant medications tend to result in a dose-related improvement in ADHD symptoms. The limited data suggest that standard dosages of antidepressants are effective. Agents with catecholaminergic activity have efficacy in ADHD, whereas those with predominately serotonergic properties appear not to be effective. The majority of studies suggest that stimulants are the most effective available agents for adults with ADHD, and these drugs remain the treatment of choice. In cases of psychiatric comorbidity, residual symptoms or adverse effects, limited data suggest benefit from combining medications. Cognitive-based psychotherapy used in association with medications may play a role in treating dynamic issues, residual symptomatology and comorbid psychopathology. Future controlled studies applying stringent diagnostic criteria and outcome methodology are necessary to define further the range of pharmacotherapeutic options for adults with ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725, Boston, MA 02114 USA. NR 56 TC 31 Z9 31 U1 2 U2 6 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PD MAY PY 1998 VL 9 IS 5 BP 347 EP 356 DI 10.2165/00023210-199809050-00002 PG 10 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA ZN645 UT WOS:000073667400002 ER PT J AU Imanaka, H Kacmarek, RM Riggi, V Ritz, R Hess, D AF Imanaka, H Kacmarek, RM Riggi, V Ritz, R Hess, D TI Expiratory phase and volume-adjusted tracheal gas insufflation: A lung model study SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-for-Respiratory-Care CY DEC 03-07, 1995 CL ORLANDO, FLORIDA SP Amer Assoc Resp Care DE expiratory phase tracheal gas insufflation; pressure control ventilation; tracheal gas insufflation; volume-adjusted tracheal gas insufflation; volume control ventilation ID RESPIRATORY-DISTRESS-SYNDROME; PRESSURE-LIMITED VENTILATION; MECHANICAL VENTILATION; PERMISSIVE HYPERCAPNIA; TIDAL VOLUME; EXCHANGE; EFFICACY; INJURY; DOGS AB Objective: To evaluate in a lung model the effects of expiratory-phase tracheal gas insufflation (expiratory-phase TGI) with both volume and pressure control ventilation, and tidal volume adjusted continuous flow TGI (volume adjusted TGI) on system pressures and volumes. Design: Single-compartment lung model, Setting: Research laboratory in a university medical center. Interventions: Expiratory-phase TGI was established, using a solenoid valve activated by the ventilator, Volume adjusted TGI was applied by reducing tidal volume (VT) by the product of TGI flow and inspiratory time. Ventilation was provided with pressure control of 20 cm H2O or volume control ventilation with VT similar to that with pressure control ventilation. A rate of 15 breaths/min and positive end expiratory pressure (PEEP) of 10 cm H2O were used throughout, Inspiratory time periods of 1.0, 1.5, 2.0, and 2.5 sees were used with TGI flows of 0, 4, 8, and 12 L/min, Lung model compliance (mL/cm H2O) and resistance (cm H2O/L/sec) combinations of 20/20, 20/5, and 50/20 were used. Measurements and Main Results: In expiratory-phase TGI with pressure control ventilation, peak alveolar pressure remained constant, PEEP increased (p < .01) and VT decreased (p < .01), In expiratory-phase TGI with volume control ventilation and volume-adjusted TGI, there were significant increases in peak alveolar pressure and PEEP (p < .01), Readjustment of VT in volume-adjusted TGI was impassible with longer inspiratory time (greater than or equal to 2 sees) and higher TGI flows (greater than or equal to 8 L/min), Conclusions: The marked increases in system pressures and volumes observed with continuous-flow TGI can be avoided with expiratory-phase TGI and volume adjusted TGI. C1 Massachusetts Gen Hosp, Resp Care Dept Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Natl Cardiovasc Ctr, Surg Intens Care Unit, Suita, Osaka, Japan. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Dept Lab, Ellison 401, Boston, MA 02114 USA. NR 14 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAY PY 1998 VL 26 IS 5 BP 939 EP 946 DI 10.1097/00003246-199805000-00033 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA ZL791 UT WOS:000073471900026 PM 9590326 ER PT J AU Cornish, JW O'Brien, CP AF Cornish, JW O'Brien, CP TI Developing medications to treat cocaine dependence: a new direction SO CURRENT OPINION IN PSYCHIATRY LA English DT Article AB Research on the development of peripheral cocaine-blocking agents represents a significant departure from previous strategies. The early results from studies of a cocaine vaccine and the findings from research on the enhancement of cocaine metabolic enzymes are reviewed. (C) 1998 Rapid Science Ltd. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Cornish, JW (reprint author), Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAY PY 1998 VL 11 IS 3 BP 249 EP 251 DI 10.1097/00001504-199805000-00002 PG 3 WC Psychiatry SC Psychiatry GA ZR109 UT WOS:000073937200002 ER PT J AU Grevelink, JM White, VR AF Grevelink, JM White, VR TI Concurrent use of laser skin resurfacing and punch excision in the treatment of facial acne scarring SO DERMATOLOGIC SURGERY LA English DT Article ID CARBON-DIOXIDE LASER; THERMAL-DAMAGE; SCARS; TISSUE AB BACKGROUND. Laser skin resurfacing has added to the numerous treatment options available for acne scarring. Adjunct modalities such as punch excision should be considered to enhance treatment outcomes. Traditionally, punch excision and grafting have been performed, followed 1-2 months later by dermabra sion. OBJECTIVE. TO determine the effectiveness of laser skin resurfacing and the concurrent use of punch excision performed at the same treatment session in the treatment of acne scarring. METHODS. Twenty-one patients with skin types I-III with mild to severe facial acne scarring were treated with a combination of laser skin resurfacing and punch excision of acne scars in the same treatment session. Baseline, postoperative, and follow-up photographs were taken and evaluated by an independent dermatologist and a laser nurse blinded to patient treatment. In addition, subjective patient assessments of improvement were obtained. RESULTS. There was a range of clinical improvement by the independent assessor of 25-50% in skin type I, 50-75% in skin type II and 50-75% in skin type III. There was a patient subjective improvement of 25-50% for skin type I, 50-75% for skin type II and 75-100% for skin type III. Postoperative hy perpigmentation teas noted in five patients and postoperative hypopigmentation was not seen in any patients. There was no wound dehiscence, evidence of infection, or hypertrophic scarring of treated areas noted on follow-up. CONCLUSION. Laser skin resurfacing with the concurrent use of punch excision improves facial acne scarring. This newly described method negates the need to delay additional resurfacing for a future visit. (C) 1998 by the American Society for Dermatologic Surgery, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser Ctr, Boston, MA 02114 USA. RP Grevelink, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Laser Ctr, 275 Cambridge St,Suite 503, Boston, MA 02114 USA. NR 17 TC 25 Z9 25 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAY PY 1998 VL 24 IS 5 BP 527 EP 530 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA ZM971 UT WOS:000073594900004 PM 9598006 ER PT J AU Bucalo, BD Mirikitani, EJ Moy, RL AF Bucalo, BD Mirikitani, EJ Moy, RL TI Comparison of skin anesthetic effect of liposomal lidocaine, nonliposomal lidocaine, and EMLA using 30-minute application time SO DERMATOLOGIC SURGERY LA English DT Article AB BACKGROUND. Liposomes are microscopic phospholipid vessels that have been utilized to extend the action of topical medications. Previous studies have demonstrated that liposomal vehicles can prolong the action of a variety of medications, including antifungals, anesthetics, interferon, and antineoplastic agents. OBJECTIVE. The purpose of this study was to examine the degree and duration of anesthesia produced by lidocaine in a liposomal vehicle compared with lidocaine in a nonliposomal vehicle and compared with EMLA. The topical preparations in this study were allowed to contact the skin for a 30-minute period prior to evaluation of anesthetic effectiveness. Unoccluded and Tega-derm-occluded topical preparations were evaluated in two separate arms of the study. MATERIALS AND METHODS. Thirteen healthy volunteers (three male, 10 female) were recruited for the nonocclusion arm of the study. Six healthy volunteers (two male, four female) were recruited for the occlusion arm of the study. Subjects with a history of allergy to lidocaine, a history of seizures, cardiac or respiratory difficulty, pregnant patients, and patients less than 18 years old were excluded. Written informed consent was obtained from all patients prior to testing. The volar forearms of the volunteers were swabbed with isopropyl alcohol and allowed to dry. A template was then utilized to mark 2 x 2-cm squares with a skin marker on both volar forearms. In total, nine squares corresponding to nine test areas were marked. The nine test preparations were applied to the test areas in a double-blinded fashion using a clean swab stick. The test preparations were then allowed to remain on the skin for 30 minutes in either occluded or nonoccluded form depending upon the arm of the study. Following the 30-minute application period, the test preparations were wiped off with clean gauze. Testing for anesthesia was performed by following a previously published method utilizing gentle pinpricks. A new pinprick apparatus was used for each patient. Pinprick testing was performed at 0, 15, 30, 60, and 90 minutes following the end of the 30-minute application period. Patients' responses to the pinprick were recorded in a binary fashion, as being either: 1) totally painless or 0) painfully sharp to any degree. Ten applications of the pinprick were applied randomly across each 2 x 2-cm test area. The number of painless applications of the pinprick out of a total of 10 applications of the pinprick was then recorded for each test area at every particular test time. In total, nine test preparations were evaluated. Analysis of the data was performed by a PhD statistical faculty consultant from the UCLA Mathematics Department. RESULTS. Liposomal lidocaine preparations evidenced longer durations of anesthesia than lidocaine preparations in nonliposomal vehicles. Five percent liposomal lidocaine preparations were statistically equivalent to EMLA in anesthetic effectiveness. CONCLUSION. Five percent liposomal lidocaine is an effective alternative topical agent for use in the attainment of temporary local anesthesia of the skin. (C) 1998 by the American Society for Dermatologic Surgery, Inc. C1 Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Bucalo, BD (reprint author), 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. NR 11 TC 51 Z9 52 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAY PY 1998 VL 24 IS 5 BP 537 EP 541 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA ZM971 UT WOS:000073594900006 PM 9598008 ER PT J AU Steil, GM Rebrin, K Mittelman, SD Bergman, RN AF Steil, GM Rebrin, K Mittelman, SD Bergman, RN TI Role of portal insulin delivery in the disappearance of intravenous glucose and assessment of insulin sensitivity SO DIABETES LA English DT Article ID PERIPHERAL INSULIN; MINIMAL MODEL; CONSCIOUS DOGS; SUPPRESSION; OUTPUT; PLASMA AB The contribution of portal insulin delivery to the disappearance of glucose administered intravenously was assessed in the present study. Paired insulin-modified intravenous glucose tolerance tests (IVGTTs) were performed in dogs in which insulin was administered into the portal vein or into a peripheral vein. Peripheral insulin levels were matched in the paired IVGTTs by adjusting the portal insulin dose in proportion to first-pass hepatic insulin extraction. Two sets of IVGTTs were performed. In the first set, hepatic insulin extraction was assumed to be 50% (insulin doses of 0.03 U/kg portal and 0.015 U/kg peripheral; n = 6); in the second set, the assumed extraction rate was reduced to 33% (0.0225 U/kg portal and 0.015 U/kg peripheral; n = 8), In the second set of experiments, a control "zero" dose (no insulin injection) was also performed. For these latter three IVGTTs, the exogenous glucose bolus was labeled with 3-[H-3]glucose (25 pCi) to separately assess insulin's effects on the rate of glucose disappearance (R-d) and endogenous glucose production (EGP), For the paired IVGTT based on 33% extraction, the area under the insulin curves after the portal insulin injection was within 2% of that observed with peripheral insulin injection (1,820 +/- 711 vs. 1,791 +/- 661 mu U/ml min; P = 0.79), For these conditions, neither the glucose profiles nor the minimal model estimate of insulin sensitivity (S-I) was significantly influenced by the higher portal insulin delivery (S-I: 3.69 +/- 0.56 vs. 3.35 +/- 0.60 10(-4) min(-1) per mu U/ml; portal vs. peripheral; P > 0.05). Analysis of the 3-[H-3]glucose tracer dynamics failed to reveal any differences in the portal versus peripheral insulin effect on glucose disappearance or production. We conclude that portal insulin delivery per se does not significantly affect insulin's ability to normalize plasma glucose during acute glucose challenges. C1 Univ So Calif, Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90033 USA. Minimed, Sylmar, CA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Bergman, RN (reprint author), Univ So Calif, Sch Med, Dept Physiol & Biophys, 1333 San Pablo St, Los Angeles, CA 90033 USA. FU NIDDK NIH HHS [DK-29867, DK-27619] NR 24 TC 20 Z9 20 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1998 VL 47 IS 5 BP 714 EP 720 DI 10.2337/diabetes.47.5.714 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZL168 UT WOS:000073405600002 PM 9588441 ER PT J AU Chevre, JC Hani, EH Stoffers, DA Habener, JF Froguel, P AF Chevre, JC Hani, EH Stoffers, DA Habener, JF Froguel, P TI Insulin promoter factor 1 gene is not a major cause of maturity-onset diabetes of the young in French Caucasians SO DIABETES LA English DT Article ID MUTATIONS; MODY C1 Inst Pasteur, CNRS EP10, F-59019 Lille, France. CHU Lille, F-59037 Lille, France. Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Froguel, P (reprint author), Inst Pasteur, CNRS EP10, 1 Rue Prof Calmette,BP 245, F-59019 Lille, France. RI Stoffers, Doris/H-6157-2012; Chevre, Jean-Claude/C-3943-2015 OI Chevre, Jean-Claude/0000-0002-5329-5231 NR 15 TC 25 Z9 27 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 MAY PY 1998 VL 47 IS 5 BP 843 EP 844 DI 10.2337/diabetes.47.5.843 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZL168 UT WOS:000073405600021 PM 9588460 ER PT J AU Ristow, M Giannakidou, E Hebinck, J Busch, K Vorgerd, M Kotzka, J Knebel, B Mueller-Berghaus, J Epplen, C Pfeiffer, A Kahn, CR Doria, A Krone, W Mueller-Wieland, D AF Ristow, M Giannakidou, E Hebinck, J Busch, K Vorgerd, M Kotzka, J Knebel, B Mueller-Berghaus, J Epplen, C Pfeiffer, A Kahn, CR Doria, A Krone, W Mueller-Wieland, D TI An association between NIDDM and a GAA trinucleotide repeat polymorphism in the X25/frataxin (Friedreich's ataxia) gene SO DIABETES LA English DT Article ID DIABETES-MELLITUS; INSULIN AB Friedreich's ataxia is the most common hereditary ataxia and is frequently associated with disturbances of glucose metabolism. This autosomal recessive disease is caused by the decreased expression of a mitochondrial protein, frataxin, encoded by the X25 gene. Homozygous expansion of a GAA repeat in the first intron of X25 inhibits frataxin expression and is associated with clinical disease. we evaluated whether heterozygous expansions of the triplet repeat in the frataxin gene X25 may be associated with NIDDM in two genetically distinct populations-one in Germany (n = 358) and the other in the U.S. (n = 292)-using a polymerase chain reaction-based assay. Intermediate expansions (10-36 repeats), which are longer than normal but not sufficient for the appearance of the ataxia phenotype, were found in 24.7 and 27.3% of these two NIDDM cohorts compared with 7.6 and 6.3% of the matched control subjects (both P < 0.001), The odds ratios were 3.36 (95% CI 1.72-6.55) for the German group and 4.01 (2.08-7.74) for the U.S. group. Therefore, we conclude that the X25/frataxin GAA repeat polymorphism is associated with NIDDM in a frequency higher than any other mutation heretofore described. Further studies are needed to elucidate the possible role of frataxin in the pathogenesis of NIDDM. C1 Joslin Diabet Ctr, Div Res, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ruhr Univ Bochum, D-4630 Bochum, Germany. Med Klin & Poliklin, Bergmannsheil, Germany. Neurol Klin, Bergmannsheil, Germany. Univ Cologne, Klin & Poliklin Innere Med 2, Cologne, Germany. Univ Cologne, Kinderklin, Cologne, Germany. RP Ristow, M (reprint author), Joslin Diabet Ctr, Div Res, Sect Cellular & Mol Physiol, Room 610,1 Joslin Pl, Boston, MA 02215 USA. RI Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 FU NIDDK NIH HHS [P30 DK36836] NR 19 TC 36 Z9 38 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1998 VL 47 IS 5 BP 851 EP 854 DI 10.2337/diabetes.47.5.851 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZL168 UT WOS:000073405600024 PM 9588463 ER PT J AU Sugarman, JR Reiber, GE Baumgardner, G Prela, CM Lowery, J AF Sugarman, JR Reiber, GE Baumgardner, G Prela, CM Lowery, J TI Use of the therapeutic footwear benefit among diabetic Medicare beneficiaries in three states, 1995 SO DIABETES CARE LA English DT Article ID SHOES; PREVENTION; DISEASE; ULCERS AB OBJECTIVE - To determine the extent to which Medicare provided reimbursement for therapeutic footwear to diabetic Medicare beneficiaries in Washington, Alaska, and Idaho in 1995. RESEARCH DESIGN AND METHODS - Using inpatient, outpatient, and durable medical equipment claims data, we selected a cohort of diabetic Medicare beneficiaries. Therapeutic footwear claims were identified using a set of billing codes intended only for the diabetes footwear benefit. People at "high risk" or "possibly increased risk" for foot problems who might benefit from therapeutic footwear were identified using a combination of International classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnostic codes in any of the databases. RESULTS - Among 608,804 beneficiaries, 10.2% (62,170) met the inclusion criteria for diabetes. Of the diabetic beneficiaries, 13.0% (8,079) had at least one "high risk" diagnosis, and 14.0% (8,686) had at least one "possibly increased risk" diagnosis. The percentage of diabetic beneficiaries with therapeutic footwear claims was 2.9% among those with diagnoses high risk, 0.70% among those viith diagnoses indicating possibly increased risk, and 0.1% among those with no diagnosis from the list. Altogether, only 0.6% of beneficiaries meeting the diabetes case ascertainment criteria had a therapeutic footwear claim in 1995. CONCLUSIONS - Few diabetic Medicare beneficiaries in Washington, Alaska, and Idaho had claims for reimbursement for therapeutic footwear in 1995. The low utilization of the footwear benefit may represent an important opportunity to improve care for Medicare beneficiaries with diabetes. Further work should be done to characterize the use of the benefit in other regions and to assess whether the low level of usage reflects underutilization. C1 PRO West, Seattle, WA USA. Univ Washington, Sch Med, Dept Family Med, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Hlth Care Financing Adm, Seattle, WA USA. RP Sugarman, JR (reprint author), PRO West, 10700 Meridian Ave N,Suite 100, Seattle, WA USA. EM wapro.jsugarma@sdps.org NR 15 TC 17 Z9 17 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1998 VL 21 IS 5 BP 777 EP 781 DI 10.2337/diacare.21.5.777 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZK207 UT WOS:000073296100017 PM 9589239 ER PT J AU Reil, H Bukovsky, AA Gelderblom, HR Gottlinger, HG AF Reil, H Bukovsky, AA Gelderblom, HR Gottlinger, HG TI Efficient HIV-1 replication can occur in the absence of the viral matrix protein SO EMBO JOURNAL LA English DT Article DE cytoplasmic domain; envelope; HIV-1; matrix protein; virus replication ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 ENVELOPE GLYCOPROTEIN; NUCLEAR-LOCALIZATION SIGNAL; NONDIVIDING CELLS; PLASMA-MEMBRANE; CORE DOMAIN; INFECTIVITY; GENE; GAG; REGION AB Matrix (MA), a major structural protein of retroviruses, is thought to play a critical role in several steps of the HIV-1 replication cycle, including the plasma membrane targeting of Gag, the incorporation of envelope (Env) glycoproteins into nascent particles, and the nuclear import of the viral genome in nondividing cells. We now show that the entire MA protein is dispensable for the incorporation of HIV-1 Env glycoproteins with a shortened cytoplasmic domain. Furthermore, efficient HIV-1 replication in the absence of up to 90% of MA was observed in a cell line in which the cytoplasmic domain of Env is not required. Additional compensatory changes in Gag permitted efficient virus replication even if all of MA was replaced by a heterologous membrane targeting signal. Viruses which lacked the globular domain of MA but retained its N-terminal myristyl anchor exhibited an increased ability to form both extracellular and intracellular virus particles, consistent with a myristyl switch model of Gag membrane targeting. Pseudotyped HIV-1 particles that lacked the structurally conserved globular head of MA efficiently infected macrophages, indicating that MA is dispensable for nuclear import in terminally differentiated cells. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Robert Koch Inst, D-1000 Berlin, Germany. RP Gottlinger, HG (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM Heinrich_Gottlinger@DFCI.harvard.edu FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28691, AI29873] NR 53 TC 190 Z9 194 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 1 PY 1998 VL 17 IS 9 BP 2699 EP 2708 DI 10.1093/emboj/17.9.2699 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZN307 UT WOS:000073632800024 PM 9564051 ER PT J AU Merchant, SN McKenna, MJ Rosowski, JJ AF Merchant, SN McKenna, MJ Rosowski, JJ TI Current status and future challenges of tympanoplasty SO EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY LA English DT Article DE conductive hearing loss; middle ear mechanics; tympanoplasty ID HUMAN MIDDLE-EAR; TYMPANIC-MEMBRANE; V TYMPANOPLASTY; REPLACEMENT PROSTHESES; INPUT IMPEDANCE; SURGERY; MODEL; MECHANICS; IMPLANTS; CAT AB Four decades after the introduction of tympanoplasty, the goal of achieving stable and long-term hearing improvement after tympanoplasty surgery for chronic otitis media continues to be elusive. In this review, we focus on the current status of our understanding of the mechanics and pathology of the middle ear after tympanoplasty surgery. We also analyze some problems and challenges faced by clinicians and basic scientists in the quest for improved postoperative hearing results. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 86 TC 28 Z9 35 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0937-4477 J9 EUR ARCH OTO-RHINO-L JI Eur. Arch. Oto-Rhino-Laryn. PD MAY PY 1998 VL 255 IS 5 BP 221 EP 228 DI 10.1007/s004050050047 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA ZR258 UT WOS:000073956100001 PM 9638462 ER PT J AU Robbins, SJ Ehrman, RN AF Robbins, SJ Ehrman, RN TI Cocaine use is associated with increased craving in outpatient cocaine abusers SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PHARMACOTHERAPEUTIC ADJUVANT THERAPY; CUE REACTIVITY; INPATIENT TREATMENT; ALCOHOL DEPENDENCE; INDUCED MOODS; SMOKING; RELAPSE; PREDICTORS; DESIPRAMINE; ABSTINENCE AB Sixty-one cocaine abuse patients provided self-reports of craving and urine samples 3 times a week. Within-subject analyses revealed several relationships between the measures. First, peak craving levels were higher for 2-3-day intervals during which cocaine use had occurred than for preceding or following abstinent intervals. Second, average craving ratings during cocaine use intervals were double the ratings given during abstinent intervals. Third, cocaine use was 4 times more likely to occur during a period of elevated craving than during comparison intervals. Finally, participants who provided at least 1 positive urine sample reported more craving increases over 4 weeks than did abstinent individuals. These results demonstrate a strong association between craving increases and naturally occurring cocaine use but do not allow a determination of whether craving caused cocaine use or cocaine use caused craving. C1 Beaver Coll, Dept Psychol, Glenside, PA 19038 USA. Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Psychiat Serv, Philadelphia, PA USA. RP Robbins, SJ (reprint author), Beaver Coll, Dept Psychol, 450 S Easton Rd, Glenside, PA 19038 USA. FU NIDA NIH HHS [DA03008] NR 59 TC 19 Z9 19 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD MAY PY 1998 VL 6 IS 2 BP 217 EP 224 DI 10.1037/1064-1297.6.2.217 PG 8 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA ZN471 UT WOS:000073649200011 PM 9608354 ER PT J AU Sibayan, SAB Latina, MA Sherwood, ME Flotte, TJ White, K AF Sibayan, SAB Latina, MA Sherwood, ME Flotte, TJ White, K TI Apoptosis and morphologic changes in drug-treated trabecular meshwork cells in vitro SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE apoptosis; dexamethasone; epinephrine; 5-fluorouracil; mitomycin-C; pilocarpine; timolol; trabecular meshwork ID MITOMYCIN-C; DEOXYRIBONUCLEIC-ACID; OCULAR PENETRATION; ANTICANCER AGENTS; DNA FRAGMENTATION; DENTATE GYRUS; DEATH; GLAUCOMA; DEXAMETHASONE; ACTIVATION AB Using an in vitro culture system, we investigated whether bovine trabecuIar meshwork cells undergo apoptosis (programmed cell death) following exposure to anti-glaucoma medications (timolol, pilocarpine and epinephrine) and known inducers of apoptosis (5-fluorouracil, mitomycin-C and dexamethasone). Third to fifth passage bovine trabecular meshwork cells were grown to confluence and incubated for 1-12 days in growth media with timolol (1-1000 mu M), pilocarpine (15-15000 mu M), epinephrine (5-5000 mu M), 5-fluorouracil (10-100 mu g ml(-1)), mitomycin-C (0.01-100 mu g ml(-1)) and dexamethasone (0.01-100 mu M). The cultures were evaluated for apoptosis by phase-contrast microscopy, transmission electron microscopy and in situ apoptosis labeling. 5-Fluorouracil (10-100 mu g ml(-1)), mitomycin-C (0.1-100 mu g ml-l) and epinephrine (500-5000 mu M) induced apoptosis in a dose and time-dependent manner. Timolol, pilocarpine, and dexamethasone-treated specimens did not show evidence of apoptosis at any of the concentrations tested. Trabecular meshwork cells incubated in timolol (100-1000 mu M) developed cytoplasmic granules, and specimens treated with pilocarpine (15000 mu M) developed cytoplasmic vacuoles. These granules and vacuoles have the appearance of secondary lysosomes. Dexamethasone-treated cells developed an increased number of mitochondria. This study suggests that the trabecular meshwork may undergo apoptosis following exposure to 5-fluorouracil, mitomycin-C and epinephrine. Timolol, pilocarpine and dexamethasone did not induce apoptosis. However, these drugs can incite characteristic morphologic changes in cultured trabecular meshwork cells. (C) 1998 Academic Press Limited. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA USA. RP Sibayan, SAB (reprint author), Med Bldg,Room 401,San Miguel Ave, Pasig City 1600, Philippines. NR 46 TC 18 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 1998 VL 66 IS 5 BP 521 EP 529 DI 10.1006/exer.1997.0458 PG 9 WC Ophthalmology SC Ophthalmology GA ZR988 UT WOS:000074036400002 PM 9628799 ER PT J AU ter Haar, E AF ter Haar, E TI Taxanes and other microtubule stabilising agents SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE discodermolide; eleutherobin; epithilones; multi-drug resistance; sarcodictyin; Taxol((R)); Taxotere((R)); water solubility ID TAXOL; DISCODERMOLIDE; DERIVATIVES; PRODRUGS; DRUG AB Paclitaxel (Taxol(R)) and docetaxel (Taxotere(R)) are relatively new drugs used in cancer therapy and have shown great promise in the treatment of a variety of cancers. The taxane therapy, however, encounters two major problems. One problem is the low solubility of both paclitaxel and docetaxel; the second problem is multi-drug resistance. In the patent literature from 1995 - 1997 these two problems have been the main focus of research in the taxane field. Numerous taxoids have been disclosed with improved solubility, mainly by acylation of the C-2' and C-7 hydroxyls. To reduce the multi-drug resistance susceptibility of the drugs, alterations on the taxane core and the phenylisoserine ring have been made. The patent literature also reports the discovery of new classes of compounds (epothilones, discodermolides, eleutherobins and sarcodictyins) that are structurally dissimilar from taxanes but have microtubule stabilisation activity and are potent inhibitors of cancer cells and paclitaxel-resistant cancer cells. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP ter Haar, E (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 36 TC 16 Z9 16 U1 1 U2 4 PU ASHLEY PUBL LTD PI LONDON PA 1ST FL, THE LIBRARY, 1 SHEPHERDS HILL HIGHGATE, LONDON, ENGLAND N6 5QJ SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD MAY PY 1998 VL 8 IS 5 BP 571 EP 586 PG 16 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZM965 UT WOS:000073594300007 ER PT J AU Eroglu, A Toth, TL Toner, M AF Eroglu, A Toth, TL Toner, M TI Alterations of the cytoskeleton and polyploidy induced by cryopreservation of metaphase II mouse oocytes SO FERTILITY AND STERILITY LA English DT Article DE cryopreservation; cytoskeleton; digyny; fertilization; oocyte ID MEIOTIC SPINDLE; INVITRO FERTILIZATION; FROZEN; ORGANIZATION; DIMETHYLSULFOXIDE; CHROMOSOMES; SURVIVAL; EGG AB Objective: To determine cryopreservation-induced alterations in the cytoskeleton of metaphase ii mouse oocytes and the implications of these alterations in functionality of the cytoskeleton and polyploidy after fertilization. Design: Comparative study. Setting: Clinical and academic research environment at a medical school teaching hospital. Intervention(s): Oocytes were frozen using a slow-cooling (0.5 degrees C/min) and slow-thawing (8 degrees C/min) protocol in 1.5 M dimethyl sulfoxide and 0.2 hi sucrose and were analyzed before and after fertilization. Main Outcome Measure(s): Cytoskeletal alterations. fertilization, and polyploidy rates. Result(s): When analyzed immediately after thawing, the oocytes displayed dramatic cytoskeletal alterations. Only slight recovery was observed upon removal of the cryoprotectants. However, incubation after thawing of 1 hour at 37 degrees C completely reestablished a normal microfilament and microtubule pattern while partially restoring normal spindle morphology and chromosome alignment. Accordingly, insemination immediately after removal of cryoprotectants resulted in a significantly decreased fertilization rate and aberrant dynamics of cytoskeleton-dependent events. whereas oocytes inseminated after the post-thaw incubation displayed fertilization rates and cytoskeletal dynamics comparable to those in controls. Cryopreservation did not increase polyspermy but significantly increased digyny when the oocytes were inseminated after the post-thaw incubation. All digynic eggs displayed an abnormal spindle remnant in comparison with diploid or polyspermic eggs. Conclusion(s): cl brief period of incubation after thawing allows recovery and positively affects fertilization and cytoskeletal dynamics. Cryopreservation does not impair the functionality of microfilaments and cytoplasmic microtubules during postfertilization events. Our findings suggest that the increased rate of digyny in cryopreserved oocytes may be related to the spindle disorganization, leading to failure in segregation of the chromosomes, rather than to direct malfunction of the microfilaments in polar body formation. (C) 1998 by American Society for Reproductive Medicine. C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, 55 Fruit St,GRB 1401, Boston, MA 02114 USA. NR 25 TC 115 Z9 125 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 1998 VL 69 IS 5 BP 944 EP 957 DI 10.1016/S0015-0282(98)00030-2 PG 14 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZJ796 UT WOS:000073254100026 PM 9591507 ER PT J AU McGibbon, CA Krebs, DE AF McGibbon, CA Krebs, DE TI The influence of segment endpoint kinematics on segmental power calculations SO GAIT & POSTURE LA English DT Article DE gait analysis; segment power; joint power; power imbalance; joint gap ID MECHANICAL ENERGY; CENTER LOCATION; MODEL; WALKING; GAIT; FOOT AB Segment power can be estimated from the rate of change of segment energy or from segment endpoint dynamics. The inequality between these two calculations is termed the segment power imbalance (Delta P). Explanations for this imbalance have been largely anecdotal. We used 3D gait data for 20 young, healthy adults to show experimentally that Delta P is always zero when rigid body assumptions are strictly adhered to. We show mathematically and experimentally that Delta P is non-zero (range: < 1-100 W) when segment endpoints move relative to the segment center of mass (COM). We also show that Lagrangian numerical differentiation of segment endpoint trajectories produce small velocity artifacts which result in observable Delta P (range: 0.3-5 W). The benefits of obtaining a small Delta P was found to be offset by large discrepancies (range: 8-54 W) in joint power across the joint gap. For the foot, large Delta P (range: 23-106 W) was observed when the distal velocity component included velocity of the center of pressure relative to the foot's COM. Our results suggest that, unless interpreted carefully, segment power calculations can potentially lead to erroneous clinical judgement. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Dept Phys Therapy, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. NR 15 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD MAY PY 1998 VL 7 IS 3 BP 237 EP 242 DI 10.1016/S0966-6362(97)00041-6 PG 6 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA ZY043 UT WOS:000074580900007 ER PT J AU Barnes, CJ Lee, M AF Barnes, CJ Lee, M TI Chemoprevention of spontaneous intestinal adenomas in the adenomatous polyposis coli Min mouse model with aspirin SO GASTROENTEROLOGY LA English DT Article ID CYCLOOXYGENASE-2 LEVELS; COLORECTAL-CANCER; SULINDAC SULFIDE; MUCOSAL INJURY; CARCINOGENESIS; APOPTOSIS; PROLIFERATION; RISK; TUMORIGENESIS; INHIBITION AB Background & Aims: Colorectal cancer is a significant source of morbidity and mortality in the United States and other Western countries. Epidemiological and experimental data indicate that regular use of aspirin reduces colon cancer risk. This study was designed to determine if aspirin would significantly inhibit gastrointestinal tumor formation in a mouse model of familial adenomatous polyposis. Methods: Six-week-old male and female C57BL/6J +/+ (control) and C57BL/6J Apc(Min)/+ (Min) mice were fed either a control AlN-76A diet or one supplemented with 250 or 500 parts per million (ppm) aspirin (n = 6 per group) for 7 weeks. Results: All of the Min mice, but no control mice, developed gastrointestinal tumors. Aspirin significantly reduced tumor multiplicity (number of tumors per mouse) in the small intestine, but not the colon, from an average of 35.8 tumors per mouse (control diet) to 16 and 18.5 tumors per mouse with 250 and 500 ppm aspirin, respectively. Total tumor load (sum of tumor diameters per mouse) was also significantly reduced, from 93.2 mm in total diameter to 40.4 and 45.0 mm with 250 and 500 ppm aspirin, respectively. Results were not significantly different because of sex or aspirin dose. Conclusions: High doses of aspirin are effective chemopreventive agents in a mouse model of spontaneous intestinal tumor formation. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Gastroenterol & Nutr, San Antonio, TX 78284 USA. Vet Affairs Med Ctr, San Antonio, TX USA. RP Lee, M (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Gastroenterol & Nutr, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCI NIH HHS [P30 CA 54174] NR 32 TC 125 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1998 VL 114 IS 5 BP 873 EP 877 DI 10.1016/S0016-5085(98)70305-1 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZJ817 UT WOS:000073256500006 PM 9558273 ER PT J AU Wershil, BK Castagliuolo, I Pothoulakis, C AF Wershil, BK Castagliuolo, I Pothoulakis, C TI Direct evidence of mast cell involvement in Clostridium difficile toxin A-induced enteritis in mice SO GASTROENTEROLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; CONNECTIVE-TISSUE-TYPE; DEFICIENT W/WV MICE; RAT ILEUM; GRANULOCYTE INFILTRATION; SMALL-INTESTINE; RABBIT ILEUM; NU MICE; C-KIT; NEUTROPHIL AB Background & Aims: The pathogenesis of Clostridium difficile toxin A-induced intestinal inflammation is not completely understood. The aim of this study was to define the contribution of mast cells to the fluid secretion and neutrophil infiltration associated with toxin A-induced enteritis. Methods: Fluid secretion and neutrophil infiltration in toxin A-or buffer-challenged ileal loops were assessed in normal, mast cell-deficient, and mast cell-deficient Kit(W)/Kit(W-v) mice that had undergone selective repair of their mast cell deficiency. The effect of a specific substance P-receptor antagonist was also studied. Results: Intestinal fluid secretion and neutrophil recruitment were significantly diminished in mast cell-deficient Kit(W)/Kit(W-v) and mast cell-deficient Mgf(Sl)/Mgf(Sl-d) mice compared with the respective normal mice. Mast cell-reconstituted Kit(W)/Kit(W-v) mice showed responses similar to the normal congenic mice. Administration of a specific substance P-receptor antagonist (CP-96,345) reduced toxin A-induced intestinal fluid secretion and inhibited neutrophil infiltration in normal, mast cell-deficient Kit(W)/Kit(W-v), and mast cell-reconstituted Kit(W)/Kit(W-v) mice. Conclusions: C. difficile toxin A elicits intestinal fluid secretion and neutrophil infiltration by both mast cell-dependent and -independent pathways, and substance P participates in both pathways. C1 Childrens Hosp & Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Med Ctr, Div Expt Pathol, Boston, MA USA. Beth Israel Med Ctr, Div Gastroenterol, Boston, MA USA. RP Wershil, BK (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, 149 13th St 1493404, Charlestown, MA USA. EM bwershil@bidmc.harvard.edu RI CASTAGLIUOLO, IGNAZIO/K-9963-2016 OI CASTAGLIUOLO, IGNAZIO/0000-0001-9888-7030 FU NIDDK NIH HHS [DK33506, DK40561, DK46819] NR 45 TC 84 Z9 86 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1998 VL 114 IS 5 BP 956 EP 964 DI 10.1016/S0016-5085(98)70315-4 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZJ817 UT WOS:000073256500017 PM 9558284 ER PT J AU Richardson, JH Hofmann, W Sodroski, JG Marasco, WA AF Richardson, JH Hofmann, W Sodroski, JG Marasco, WA TI Intrabody-mediated knockout of the high-affinity IL-2 receptor in primary human T cells using a bicistronic lentivirus vector SO GENE THERAPY LA English DT Article DE lentivirus vector; IRES; VSV-G protein; single-chain antibody; IL-2R alpha ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL VECTORS; GENE-EXPRESSION; NONDIVIDING CELLS; INTERLEUKIN-2 RECEPTOR; NUCLEAR-LOCALIZATION; MATRIX PROTEIN; MESSENGER-RNA; TYPE-1 DNA; 2 GENES AB A bicistronic human immunodeficiency virus type 1 (HIV-1)-based vector is described in which the expression of a selectable marker and a second gene of interest are for coupled by means of an internal ribosome entry site. The vector provides high-level expression of We coselected gene in approximately 90% of transduced cells and has been used to express an endoplasmic reticulum-targeted antibody (intrabody) directed against a subunit receptor, IL-2R alpha. In the established T cell line and also in primary human T cells stably transduced with the intrabody vector, the cell surface expression of IL-2R alpha could be reduced to a low or undetectable level. Responsiveness to IL-2 was reduced 10-fold in We IL-2R alpha-negative cells, consistent with a lack of high-affinity IL-2 receptors. Pseudotyping of the HIV-I core with the vesicular stomatitis virus G protein improved particle stability by two- to three-fold and enhanced vector entry into established T cell lines up to 230-fold. Vector entry into primary human T cells was most efficient when the amphotropic murine leukemia virus envelope was used. The forced, high-expression capability of the bicistronic vector, together with the capacity of HIV-1 vectors to infect nondividing cells, make this an attractive tool for the genetic manipulation of primary cell types. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Div Human Retrovirol, Boston, MA 02115 USA. RP Richardson, JH (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Div Human Retrovirol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P30 CA06516]; NIAID NIH HHS [P30 AI28691, AI28785] NR 60 TC 24 Z9 26 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 1998 VL 5 IS 5 BP 635 EP 644 DI 10.1038/sj.gt.3300644 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZN010 UT WOS:000073598700009 PM 9797868 ER PT J AU Silverstein, JT Breininger, J Baskin, DG Plisetskaya, EM AF Silverstein, JT Breininger, J Baskin, DG Plisetskaya, EM TI Neuropeptide Y-like gene expression in the salmon brain increases with fasting SO GENERAL AND COMPARATIVE ENDOCRINOLOGY LA English DT Article ID STIMULATES GROWTH-HORMONE; GONADOTROPIN-II SECRETION; CENTRAL-NERVOUS-SYSTEM; PARAVENTRICULAR NUCLEUS; GOLDFISH PITUITARY; FEMALE GOLDFISH; ENERGY-BALANCE; FOOD-INTAKE; PEPTIDE YY; INSULIN AB In mammals there is a well-established connection between neuropeptide Y (NPY) and the balance between energy intake and expenditure: NPY stimulates food intake and the hypothalamus shows a dramatic increase in NPY mRNA in response to fasting. The widespread occurrence of NPY in the brains of all vertebrates investigated raises the possibility that NPY may be involved in food intake and energy balance regulation in nommammalian vertebrates as well. We used in situ hybridization to examine whether brain NPY-like gene expression is involved in energy balance regulation in salmon. A radiolabeled oligonucleotide probe was employed to screen the salmon forebrain and parts of the midbrain for NPY-like mRNA. Distribution of NPY-Like gene expression was determined, followed by examination of brains from fed or food-deprived chinook and coho salmon. Regions expressing NPY-like mRNA were the caudoventral telencephalon, preoptic area, thalamus, optic tectum, and caudal hypothalamus. The region showing a difference in NPY-like gene expression between fed and fasted individuals was the preoptic area of the hypothalamus where significantly greater hybridization signal area was found with fasting. Plasma insulin levels were also shown to differ, with fasted animals having significantly lower insulin levels. These results suggest that the role of NPY-like peptides in the regulation of energy balance may have arisen early in vertebrate evolution. (C) 1998 Academic Press. C1 Univ Washington, Sch Fisheries, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Div Metab, Seattle, WA 98108 USA. RP Silverstein, JT (reprint author), Jamie Whitten Delta States Res Ctr, Expt Stn Rd,5 Story Bldg,POB 38, Stoneville, MS 38776 USA. FU NIDDK NIH HHS [DK17047] NR 43 TC 100 Z9 111 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0016-6480 EI 1095-6840 J9 GEN COMP ENDOCR JI Gen. Comp. Endocrinol. PD MAY PY 1998 VL 110 IS 2 BP 157 EP 165 DI 10.1006/gcen.1998.7058 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZL252 UT WOS:000073414000007 PM 9570936 ER PT J AU Hosokawa, Y Arnold, A AF Hosokawa, Y Arnold, A TI Mechanism of cyclin DI (CCNDI, PRADI) overexpression in human cancer cells: Analysis of allele-specific expression SO GENES CHROMOSOMES & CANCER LA English DT Article ID HUMAN BREAST-CANCER; CENTROCYTIC LYMPHOMA; PROTEIN EXPRESSION; MAMMARY CARCINOMAS; D1; GENE; ONCOGENE; GROWTH; MUTATIONS; D1/PRAD1 AB The cyclin D11CCND1 oncogene (PRAD1) is amplified in 15% of primary human breast cancers and overexpressed in 30-50% of breast cancers, suggesting that mechanisms in addition to DNA amplification may lead to deregulated expression of this gene in breast cancer. Cyclin DI overexpression at a higher frequency than gene amplification is also seen in a variety of other tumors. Cyclin DI overexpression without amplification could result from a trans-acting regulatory disturbance or could be a consequence of a clonal regulatory mutation in one allele of the gene. We have, therefore, examined whether the overexpression of cyclin DI mRNA is derived from one parental allele or both alleles in tumor cell lines with or without amplification of the cyclin DI gene. Eight tumor cell lines, MCF-7, SK-BR-3, ZR-75-1, U-2-OS, SK-LMS-I, DLD1, HCT15, and HT29, out of 20 tumor cells initially examined were found to be heterozygous at the polymorphic Ncil sire within exon 4 of the cyclin DI gene. Polymerase chain reaction and Ncil digestion (PCR-RFLP) analysis of genomic DNA demonstrated DNA amplification of one allele in the ZR-75-1 cells and HT29 cells and no such imbalance in cyclin DI gene copy number in the other cells, consistent with Southern blot analyses. Reverse-transcription polymerase chain reaction analysis and Ncil digestion (RT-PCR-RFLP) of total cDNA revealed that the overexpressed cyclin DI mRNA is preferentially derived from the amplified allele in the ZR-75-1 and HT29 cells. In contrast, the other tumor cells overexpressed cyclin DI mRNA equally from both alleles. This finding strongly suggests that, in breast, sarcoma, and in colon cancer cells with cyclin DI overexpression and normal gene copy number, elevated levels of cyclin DI mRNA result from a trans-acting influence on both alleles rather than a clonal somatic mutation or rearrangement in or near a single cyclin DI gene. (C) 1998 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Lab Endocrine Oncol, Boston, MA 02114 USA. RP Arnold, A (reprint author), Univ Connecticut, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. FU NCI NIH HHS [CA55909] NR 32 TC 108 Z9 111 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 1998 VL 22 IS 1 BP 66 EP 71 DI 10.1002/(SICI)1098-2264(199805)22:1<66::AID-GCC9>3.0.CO;2-5 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA ZK705 UT WOS:000073352900009 PM 9591636 ER PT J AU Bergeron, L Perez, GI Macdonald, G Shi, LF Sun, Y Jurisicova, A Varmuza, S Latham, KE Flaws, JA Salter, JCM Hara, H Moskowitz, MA Li, E Greenberg, A Tilly, JL Yuan, JY AF Bergeron, L Perez, GI Macdonald, G Shi, LF Sun, Y Jurisicova, A Varmuza, S Latham, KE Flaws, JA Salter, JCM Hara, H Moskowitz, MA Li, E Greenberg, A Tilly, JL Yuan, JY TI Defects in regulation of apoptosis in caspase-2-deficient mice SO GENES & DEVELOPMENT LA English DT Article DE caspase-2; Ich1; Nedd2; apoptosis; caspases; cell death ID PROGRAMMED CELL-DEATH; AMYOTROPHIC-LATERAL-SCLEROSIS; ICE-LIKE PROTEASES; GRANZYME-B; INTERLEUKIN-1-BETA-CONVERTING ENZYME; IL-1-BETA-CONVERTING ENZYME; CONVERTING-ENZYME; INDUCE APOPTOSIS; NEURONAL DEATH; GENE CED-3 AB During embryonic development, a large number of cells die naturally to shape the new organism. Members of the caspase family of proteases are essential intracellular death effecters. Herein, we generated caspase-2-deficient mice to evaluate the requirement for this enzyme in various paradigms of apoptosis. Excess numbers of germ cells were endowed in ovaries of mutant mice and the oocytes were found to be resistant to cell death following exposure to chemotherapeutic drugs. Apoptosis mediated by granzyme B and perforin was defective in caspase-2-deficient B lymphoblasts. In contrast, cell death of motor neurons during development was accelerated in caspase-2-deficient mice. In addition, caspase-2-deficient sympathetic neurons underwent apoptosis more effectively than wild-type neurons when deprived of NGF. Thus, caspase-2 acts both as a positive and negative cell death effector, depending upon cell lineage and stage of development. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Manitoba, Manitoba Canc Treatment & Res Fdn, Manitoba Inst Cell Biol, Winnipeg, MB R3E 0V9, Canada. Childrens Hosp, Dept Neurol, Div Neurosci, Boston, MA 02115 USA. Univ Toronto, Dept Zool, Toronto, ON M5S 3G5, Canada. Univ Toronto, Dept Obstet & Gynecol, Toronto, ON M5S 3G5, Canada. Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. Temple Univ, Sch Med, Dept Biochem, Philadelphia, PA 19140 USA. Univ Maryland, Sch Med, Dept Anat, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Dept Surg, Neurosurg Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RI Moskowitz, Michael/D-9916-2011; Jurisicova, Andrea/E-4580-2013 FU NIA NIH HHS [R01 AG012279, R01-AG12279]; NICHD NIH HHS [R01-HD34226] NR 51 TC 511 Z9 521 U1 2 U2 6 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1998 VL 12 IS 9 BP 1304 EP 1314 DI 10.1101/gad.12.9.1304 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA ZN219 UT WOS:000073621800008 PM 9573047 ER PT J AU Shepel, LA Lan, H Haag, JD Brasic, GM Gheen, ME Simon, JS Hoff, P Newton, MA Gould, MN AF Shepel, LA Lan, H Haag, JD Brasic, GM Gheen, ME Simon, JS Hoff, P Newton, MA Gould, MN TI Genetic identification of multiple loci that control breast cancer susceptibility in the rat SO GENETICS LA English DT Article ID CARCINOMA SUPPRESSOR GENE; MAMMARY CARCINOGENESIS; QUANTITATIVE TRAITS; MENDELIAN FACTORS; LINKAGE MAP; 7,12-DIMETHYLBENZANTHRACENE; EXPRESSION; ASSIGNMENT; WOMEN AB We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3. These three loci map to chromosomes 2, 7, and 1, respectively, and interact additively to suppress mammary carcinoma development in the COP strain. They are responsible for a major portion of the tumor-resistant phenotype of the COP rat. No loss of heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4, has also been identified on chromosome 8 and acts in contrast to increase the number of carcinomas. These results show that mammary carcinoma susceptibility in the COP rat is a polygenic trait. Interestingly, a polymorphism in the human genomic region homologous to the rat Mcs4 region is associated with an increased breast cancer risk in African-American women. The isolation of the !Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention. C1 Univ Wisconsin, Dept Human Oncol, Madison, WI 53792 USA. Univ Wisconsin, Dept Biostat, Madison, WI 53792 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Waltham, MA 02154 USA. Harvard Univ, Sch Med, Waltham, MA 02154 USA. RP Gould, MN (reprint author), Univ Wisconsin, Dept Human Oncol, K4-332,600 Highland Ave, Madison, WI 53792 USA. RI Hoff, Peter/H-4040-2011; Gould, Michael/C-7414-2014 FU NCI NIH HHS [CA28954] NR 36 TC 70 Z9 70 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1998 VL 149 IS 1 BP 289 EP 299 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA ZN696 UT WOS:000073672500023 PM 9584103 ER PT J AU Schmidt-Erfurth, U Miller, J Sickenberg, M Bunse, A Laqua, H Gragoudas, E Zografos, L Birngruber, R van den Bergh, H Strong, A Manjuris, U Fsadni, M Lane, AM Piguet, B Bressler, NM AF Schmidt-Erfurth, U Miller, J Sickenberg, M Bunse, A Laqua, H Gragoudas, E Zografos, L Birngruber, R van den Bergh, H Strong, A Manjuris, U Fsadni, M Lane, AM Piguet, B Bressler, NM TI Photodynamic therapy of subfoveal choroidal neovascularization: Clinical and angiographic examples SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 94th Congress of the German-Ophthalmological-Society CY SEP 21-24, 1996 CL MANNHEIM, GERMANY SP German Ophthalmol Soc ID LOW-DENSITY-LIPOPROTEIN; RECEPTOR-MEDIATED UPTAKE; AGE-RELATED MACULOPATHY; DELIVERED BENZOPORPHYRIN; MACULAR DEGENERATION; ENDOTHELIAL-CELLS; TUMOR; IDENTIFICATION; PREVALENCE; PORPHYRINS AB Background: Conventional photocoagulation of subfoveal choroidal neovascularization (CNV) is often accompanied by visual loss due to thermal damage to adjacent retinal structures. Photodynamic therapy (PDT) allows vascular occlusion by selective photochemical destruction of vascular endothelial cells only. In a pilot study we evaluated the use of PDT in CNV. Methods: In a clinical phase I/II trial, patients with subfoveal CNV were treated with PDT. Benzoporphyrin derivative monoacid ring A (BPD) was used as sensitizer at a drug dose of 6 mg/m(2) or 12 mg/m(2). Irradiation was performed via a diode laser emitting at 690 nm coupled into a slit lamp. Safe and maximum tolerated light doses were defined by dose escalation from 25 to 150 J/cm(2). Photodynamic effects were documented ophthalmoscopically and angiographically. Results: Sixty-one patients received a single course of BPD-PDT. Preliminary results suggest no damage to retinal structures within the treated area clinically. Retinal perfusion was not altered, while CNV demonstrated immediate absence of fluorescein leakage in the majority of lesions subsequent to PDT. At optimized parameters (6 mg/m(2) and 50 J/cm(2)) complete cessation of leakage from classic CNV occurred in 100% of cases at 1 week and in 50% at week 4. In 70-80% of classic CNV, leakage reappeared at week 12, but markedly less than before treatment. Conclusion: PDT allows temporary absence of leakage from CNV with preservation of visual acuity. The long-term prognosis of CNV secondary to age-related macular degeneration treated with repeated courses of PDT is being evaluated in a phase III trial. C1 Univ Lubeck, Hosp Eye, D-23538 Lubeck, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Hop Jules Gonin, Lausanne, Switzerland. QLT Phototherapeut Inc, Vancouver, BC, Canada. CIBA Vis Ophthalm, Bulach, Switzerland. Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Baltimore, MD 21205 USA. RP Schmidt-Erfurth, U (reprint author), Univ Lubeck, Hosp Eye, Ratzaburger Allee 160, D-23538 Lubeck, Germany. RI Birngruber, Reginald/Q-2342-2016 NR 29 TC 86 Z9 88 U1 1 U2 2 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 MAY PY 1998 VL 236 IS 5 BP 365 EP 374 DI 10.1007/s004170050092 PG 10 WC Ophthalmology SC Ophthalmology GA ZM545 UT WOS:000073550900008 PM 9602321 ER PT J AU Faierman, E Jupiter, JB AF Faierman, E Jupiter, JB TI The management of acute fractures involving the distal radio-ulnar joint and distal ulna SO HAND CLINICS LA English DT Article ID COLLES FRACTURE; WRIST; HEAD; REPLACEMENT; INJURIES; FOREARM; COMPLICATIONS; DISLOCATION; CHILDREN; ELBOW AB The acute management of fractures involving the distal radio-ulnar joint and distal ulna is controversial. The primary goal is recognition and differentiation between stable and unstable fracture patterns. Although an operative approach is adopted in the treatment of these injuries, the optimal management protocol awaits good prospective randomized studies. C1 Massachusetts Gen Hosp, Orthopaed Hand Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Orthopaed Hand Serv, Dept Orthopaed Surg, WACC 527,15 Parkman St, Boston, MA 02114 USA. NR 92 TC 18 Z9 18 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 0749-0712 J9 HAND CLIN JI Hand Clin. PD MAY PY 1998 VL 14 IS 2 BP 213 EP + PG 18 WC Orthopedics SC Orthopedics GA ZN677 UT WOS:000073670600007 PM 9604154 ER PT J AU Schouten, R AF Schouten, R TI The psychotherapist-patient privilege SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article C1 Massachusetts Gen Hosp, Law & Psychiat Serv, Boston, MA 02114 USA. RP Schouten, R (reprint author), Massachusetts Gen Hosp, Law & Psychiat Serv, Warren 605,Fruit St, Boston, MA 02114 USA. NR 2 TC 2 Z9 2 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1998 VL 6 IS 1 BP 44 EP 48 PG 5 WC Psychiatry SC Psychiatry GA ZQ914 UT WOS:000073915700005 PM 10370432 ER PT J AU Tuori, A Uusitalo, HM Burgeson, RE Miner, JH Sanes, JR Virtanen, I AF Tuori, A Uusitalo, HM Burgeson, RE Miner, JH Sanes, JR Virtanen, I TI Laminin alpha 5-chain is expressed early and widely during the development of the anterior segment of rat eye SO HISTOCHEMICAL JOURNAL LA English DT Article ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; HOMOZYGOUS NONSENSE MUTATION; CORNEAL BASEMENT-MEMBRANE; CHAIN GENE; DIFFERENTIAL EXPRESSION; NEUROMUSCULAR-JUNCTION; EXTRACELLULAR-MATRIX; BASAL LAMINAE; COLLAGEN-IV; MORPHOGENESIS AB The distribution of a novel laminin alpha 5-chain in the basement membranes of the anterior segment of rat eye was studied. Frozen sections of embryonic day (E)16-17, post-natal day (P)2, 5, 10, 15 and 30 and adult rat eyes were immunostained for laminin chains alpha 2, alpha 5, beta 1, beta 2 and gamma 1 and for laminin-5, as well as for EHS-laminin, to visualize all basement membranes. Laminin alpha 5-, beta 1- and gamma 1-chain immunoreactivities were found in the basement membranes of the inner and outer layers of optic cup, lens epithelium, further corneal epithelium and skin of the eyelids in E16-17 rat eyes. In P2 and older rat eyes, laminin alpha 5-, beta 1- and gamma 1-chains were all seen in the basement membranes of the corneal and conjunctival epithelium, Descemet's membrane, lens epithelium, ciliary processes, blood vessels and skin of the eyelids. There was a change in the expression pattern of laminin alpha 5, beta 1- and gamma 1-chains in Descemet's membrane from the endothelial side of the membrane (P2-P15 eyes) to both sides of the membrane after P30. Immunoreactivity for laminin-5 was weak in the basement membrane of E16-17 epidermis, but strong in the basement membrane of corneal, conjunctival and eyelid epithelium in P2 and older rat eyes. Laminin alpha 2- and beta 2-chains were seen in conjunctival and uveal blood vessels in P15 and older rat eyes. The laminin beta 2-chain emerged into the basement membrane of conjunctival epithelium in P30 and older rat eyes, suggesting a role for the laminin beta 2-chain in the maturation of conjunctiva. The results suggest that laminin alpha 5-chain, possibly in laminin-10 (alpha 5 beta 1 gamma 1), is early and widely expressed in the basement membranes of developing and adult rat eye and, further, that laminin alpha 5-chain is a major laminin a-chain, partly in coexpression with the alpha 3-chain of laminin-5 in the basement membranes of the anterior segment of the eye in developing and adult rats. (C) 1998 Chapman & Hall. C1 Univ Helsinki, Inst Biomed, Dept Anat, FIN-00014 Helsinki, Finland. Univ Tampere, Sch Med, Dept Ophthalmol, FIN-33101 Tampere, Finland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Washington Univ, Sch Med, Dept Med, Div Renal, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Tuori, A (reprint author), Univ Helsinki, Inst Biomed, Dept Anat, POB 9 Siltavuorenpenger 20 A, FIN-00014 Helsinki, Finland. NR 40 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0018-2214 J9 HISTOCHEM J JI Histochem.J. PD MAY PY 1998 VL 30 IS 5 BP 375 EP 381 DI 10.1023/A:1003214620214 PG 7 WC Cell Biology SC Cell Biology GA ZK468 UT WOS:000073323900010 ER PT J AU Nance, MA Raabe, WA Midani, H Kolodny, EH David, WS Megna, L Pericak-Vance, MA Haines, JL AF Nance, MA Raabe, WA Midani, H Kolodny, EH David, WS Megna, L Pericak-Vance, MA Haines, JL TI Clinical heterogeneity of familial spastic paraplegia linked to chromosome 2p21 SO HUMAN HEREDITY LA English DT Article DE spastic paraplegia; genetic linkage; chromosome 2 ID LINKAGE ANALYSIS; LOCUS AB The clinical features of four families with autosomal dominant spastic paraparesis (FSP) are described, along with the results of linkage analysis to markers from the regions of chromosomes 2, 14, and 15 which are known to contain spastic paraplegia genes. AU families had 'pure' spastic paraparesis (FSP), but the severity of symptoms varied widely among families, and other mild neurologic signs were observed in some subjects. Although no family individually yielded a lod score >3.0, all families yielded, positive lod scores with chromosome 2 markers, and a maximal lod score of 5.7 was obtained for the families combined using marker D2S352. There was no evidence of linkage to chromosome 14 or 15 in any of the families. C1 Hennepin Cty Med Ctr, Dept Neurol, Minneapolis, MN 55415 USA. Vet Adm Med Ctr, Minneapolis, MN 55417 USA. NYU, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pk Nicollet Clin, St Louis Pk, MN 55426 USA. Vanderbilt Univ, Nashville, TN USA. RP Nance, MA (reprint author), Pk Nicollet Clin, 6490 Excelsior Blvd,Suite E500, St Louis Pk, MN 55426 USA. RI Haines, Jonathan/C-3374-2012 FU NINDS NIH HHS [NS23660] NR 20 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PD MAY-JUN PY 1998 VL 48 IS 3 BP 169 EP 178 DI 10.1159/000022798 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA ZN970 UT WOS:000073702300007 PM 9618065 ER PT J AU Swat, W Fujikawa, K Ganiatsas, S Yang, D Xavier, RJ Harris, NL Davidson, L Ferrini, R Davis, RJ Labow, MA Flavell, RA Zon, LI Alt, FW AF Swat, W Fujikawa, K Ganiatsas, S Yang, D Xavier, RJ Harris, NL Davidson, L Ferrini, R Davis, RJ Labow, MA Flavell, RA Zon, LI Alt, FW TI SEK1/MKK4 is required for maintenance of a normal peripheral lymphoid compartment but not for lymphocyte development SO IMMUNITY LA English DT Article ID ACTIVATED PROTEIN-KINASE; LYN-DEFICIENT MICE; AUTOIMMUNE-DISEASE; TRANSGENIC MICE; CELL-DEATH; T-CELLS; C-JUN; TRANSCRIPTION FACTOR; TARGETED DISRUPTION; CASTLEMANS DISEASE AB SAPK is a member of the group of evolutionary conserved stress-activated kinases that mediate control of cellular death and proliferation. In lymphocytes, the SAPK pathway has been implicated in signaling from antigen, costimulatory, and death receptors; SEK1, which directly activates SAPK, is required for early embryonic development and has also been reported to be essential for normal lymphocyte development. In contrast to the latter findings, we have used RAG-2-deficient blastocyst complementation to show that SEK1-deficient embryonic stem cells support unimpaired T and B lymphocyte development. Moreover, mature SEK1-deficient lymphocytes are capable of SAPK activation. Surprisingly, however, aging SEK1-deficient chimeric mice frequently develop lymphadenopathy and polyclonal B and T cell expansions. Thus, SEK1 is not required for lymphocyte development, but is required for maintaining peripheral lymphoid homeostasis. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06520 USA. Univ Massachusetts, Sch Med, Dept Biochem & Mol Biol, Worcester, MA 01605 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM alt@rascal.med.harvard.edu FU NHLBI NIH HHS [HL32262, P01 HL59561]; NIAID NIH HHS [AI20047] NR 66 TC 56 Z9 60 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1998 VL 8 IS 5 BP 625 EP 634 DI 10.1016/S1074-7613(00)80567-1 PG 10 WC Immunology SC Immunology GA ZQ611 UT WOS:000073885400010 PM 9620683 ER PT J AU Guttormsen, HK Wetzler, LM Finberg, RW Kasper, DL AF Guttormsen, HK Wetzler, LM Finberg, RW Kasper, DL TI Immunologic memory induced by a glycoconjugate vaccine in a murine adoptive lymphocyte transfer model SO INFECTION AND IMMUNITY LA English DT Article ID B STREPTOCOCCAL POLYSACCHARIDE; INFLUENZAE TYPE-B; TOXOID CONJUGATE VACCINE; IMMUNE-RESPONSE; CELL MEMORY; IMPACT; INFECTIONS; PREVENTION; PROTEIN; ANTIGEN AB We have developed an adoptive cell transfer model in mice to study the ability of a glycoprotein conjugate vaccine to induce immunologic memory for the polysaccharide moiety. We used type III capsular polysaccharide from the clinically relevant pathogen group B streptococci conjugated to tetanus toroid (GBSIII-TT) as our model vaccine, GBS are a major cause of neonatal infections in humans, and type-specific antibodies to the capsular polysaccharide protect against invasive disease. Adoptive transfer of splenocytes from mice immunized with the GBSIII-TT conjugate vaccine conferred anti-polysaccharide immunologic memory to naive recipient mice. The transfer of memory occurred in a dose-dependent manner. The observed anamnestic immune response was characterized by (i) more rapid kinetics, (ii) isotype switching from immunoglobulin M (IgM) to IgG, and (iii) 10-fold-higher levels of type III-specific IgG antibody than for the primary response in animals with cells transferred from placebo-immunized mice. The adoptive cell transfer model described in this paper can be used for at least two purposes: (i) to evaluate conjugate vaccines with different physicochemical properties for their ability to induce immunologic memory and (ii) to study the cellular interactions required for an immune response to these molecules. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston Med Ctr, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. RP Guttormsen, HK (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM hilde-kari.guttormsen@channing.harvard.edu RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [AI 23339, T32 AI-07061, T32 AI007061] NR 31 TC 40 Z9 40 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1998 VL 66 IS 5 BP 2026 EP 2032 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZL243 UT WOS:000073413100031 PM 9573085 ER PT J AU Melby, PC Tryon, VV Chandrasekar, B Freeman, GL AF Melby, PC Tryon, VV Chandrasekar, B Freeman, GL TI Cloning of Syrian hamster (Mesocricetus auratus) cytokine cDNAs and analysis of cytokine mRNA expression in experimental visceral leishmaniasis SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TRANSFORMING GROWTH-FACTOR; HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE; CELL-STIMULATING ACTIVITIES; IMMUNE INTERFERON CDNA; T-CELL; IFN-GAMMA; HUMAN INTERLEUKIN-2; FACTOR-BETA; DONOVANI INFECTIONS AB The Syrian golden hamster (Mesocricetus auratus) is uniquely susceptible to a variety of intracellular pathogens and is an excellent model for a number of human infectious diseases, The molecular basis for this high level of susceptibility is unknown, and immunological studies related to this model have been limited by the lack of available reagents, In this report we describe the cloning and sequence analysis of portions of the Syrian hamster interleukin 2 (IL-2), IL-4, gamma interferon (IFN-gamma), tumor necrosis factor alpha, IL-10, IL-12p40, and transforming growth factor beta cDNAs, In addition, we examined the cytokine response to infection with the intracellular protozoan Leishmania donovani in this animal model, Sequence analysis of the hamster cytokines revealed 69 to 93% homology with the corresponding mouse, rat, and human nucleotide sequences and 48 to 100% homology with the deduced amino acid sequences, The hamster IFN-gamma, compared with the mouse and rat homologs, had an additional 17 amino acids at the C terminus that could decrease the biological activity of this molecule and thus contribute to the extreme susceptibility of this animal to intracellular pathogens. The splenic expression of these genes in response to infection with L. donovani, the cause of visceral leishmaniasis (VL), was determined by Northern blotting. VL in the hamster is a progressive, lethal disease which very closely mimics active human disease, In this model there was pronounced expression of the Th1 cytokine mRNAs, with transcripts being detected as early as 1 week postinfection, Basal expression of IL-4 in uninfected hamsters was prominent but did not increase in response to infection with L. donovani, IL-12 transcript expression was detected at low levels in infected animals and paralleled the expression of IFN-gamma, Expression of IL-10, a potent macrophage deactivator, increased throughout the course of infection and could contribute to the progressive nature of this infection. These initial studies are the first to examine the molecular immunopathogenesis of a hamster model of VL infection and indicate that progressive disease in this model of VL is not associated with early polarization of the splenic cellular immune response toward a Th2 phenotype and away from a Th1 phenotype. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Vet Affairs Med Ctr, Med Serv, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78284 USA. RP Melby, PC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 63 TC 98 Z9 101 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1998 VL 66 IS 5 BP 2135 EP 2142 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZL243 UT WOS:000073413100046 PM 9573100 ER PT J AU Goldstein, GS Winter, HS AF Goldstein, GS Winter, HS TI Consensus Conference on the Evaluation of Drugs to Treat Children with Inflammatory Bowel Disease - Introduction SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material DE Crohn's disease; inflammatory bowel disease; pediatric; ulcerative colitis C1 Harvard Univ, Sch Med, Boston, MA USA. Medeva Grp Dev, Westport, CT USA. RP Winter, HS (reprint author), Massachusetts Gen Hosp, Pediat GI Unit, VBK 107,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 1998 VL 4 IS 2 BP 102 EP 103 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZL117 UT WOS:000073400500006 ER PT J AU Winter, HS Russell, GJ AF Winter, HS Russell, GJ TI Developmental immunology and inflammatory bowel disease SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Consensus Conference on the Evaluation of Drugs to Treat Children with Inflammatory Bowel Disease CY OCT 18-19, 1997 CL PHILADELPHIA, PENNSYLVANIA SP Crohns & Colitis Fdn Amer Inc, Schering Plough Res Inst, Hoechst Marion Roussel Inc, Procter & Gamble Pharm Inc, Solvay Pharm Inc DE Crohn's disease; immunology; lymphocytes; ulcerative colitis C1 Harvard Univ, Sch Med, Boston, MA USA. RP Winter, HS (reprint author), Massachusetts Gen Hosp, Pediat GI Unit, VBK 107,55 Fruit St, Boston, MA 02114 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 1998 VL 4 IS 2 BP 107 EP 108 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZL117 UT WOS:000073400500009 PM 9687214 ER PT J AU Sands, BE Winter, HS AF Sands, BE Winter, HS TI Biologic agents: Data in adults and children SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Consensus Conference on the Evaluation of Drugs to Treat Children with Inflammatory Bowel Disease CY OCT 18-19, 1997 CL PHILADELPHIA, PENNSYLVANIA SP Crohns & Colitis Fdn Amer Inc, Schering Plough Res Inst, Hoechst Marion Roussel Inc, Procter & Gamble Pharm Inc, Solvay Pharm Inc DE biologic agents; CD4(+) T cells; Crohn's disease; interleukin; anti-tumor necrosis factor-alpha antibodies C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Jackson 825,55 Fruit St, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 1998 VL 4 IS 2 BP 125 EP 127 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZL117 UT WOS:000073400500020 PM 9687224 ER PT J AU Winter, HS AF Winter, HS TI Summary of the workshop on biologic agents SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material C1 Harvard Univ, Sch Med, Boston, MA USA. RP Winter, HS (reprint author), Massachusetts Gen Hosp, Pediat GI Unit, VBK 107,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 1998 VL 4 IS 2 BP 127 EP 130 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZL117 UT WOS:000073400500021 ER PT J AU Winter, HS Grand, RJ Ferry, GD AF Winter, HS Grand, RJ Ferry, GD TI Summation and next steps SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Consensus Conference on the Evaluation of Drugs to Treat Children with Inflammatory Bowel Disease CY OCT 18-19, 1997 CL PHILADELPHIA, PENNSYLVANIA SP Crohns & Colitis Fdn Amer Inc, Schering Plough Res Inst, Hoechst Marion Roussel Inc, Procter & Gamble Pharm Inc, Solvay Pharm Inc DE biologic agents; Crohn's disease; methotrexate; pediatric population; ulcerative colitis C1 Massachusetts Gen Hosp, Pediat GI Unit, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. New England Med Ctr, Boston, MA 02111 USA. Texas Childrens Hosp, Houston, TX 77030 USA. RP Winter, HS (reprint author), Massachusetts Gen Hosp, Pediat GI Unit, VBK 107,55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD MAY PY 1998 VL 4 IS 2 BP 130 EP 131 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZL117 UT WOS:000073400500022 ER PT J AU Rose, DJ Zubieta, J Fischman, AJ Hillier, S Babich, JW AF Rose, DJ Zubieta, J Fischman, AJ Hillier, S Babich, JW TI Synthesis and structural characterization of the neutral indium(III) thiolate species In{(SCH2CH2)(3)N} SO INORGANIC CHEMISTRY COMMUNICATIONS LA English DT Article DE crystal structures; indium complexes; thiolate complexes ID COMPLEXES; GALLIUM; ANTIBODIES; LIGANDS AB The neutral indium(III) thiolate species In{(SCH2CH2)(3)N} was synthesized and structurally characterized, (C) 1998 Elsevier Science S.A. All rights reserved. C1 Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02214 USA. RP Zubieta, J (reprint author), Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-7003 J9 INORG CHEM COMMUN JI Inorg. Chem. Commun. PD MAY PY 1998 VL 1 IS 5 BP 164 EP 166 DI 10.1016/S1387-7003(98)00043-4 PG 3 WC Chemistry, Inorganic & Nuclear SC Chemistry GA ZZ190 UT WOS:000074704600003 ER PT J AU Beard, CJ Lamb, C Buswell, L Schneider, L Propert, KJ Gladstone, D D'Amico, A Kaplan, I AF Beard, CJ Lamb, C Buswell, L Schneider, L Propert, KJ Gladstone, D D'Amico, A Kaplan, I TI Radiation-associated morbidity in patients undergoing small-field external beam irradiation for prostate cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; small-field irradiation; complications ID QUALITY-OF-LIFE; CONSERVATIVE MANAGEMENT; COMPLICATIONS; RADIOTHERAPY; CARCINOMA; ADENOCARCINOMA; THERAPY; TUMOR AB Purpose: To quantify complication rates after small-field external beam irradiation for adenocarcinoma of the prostate in a uniformly treated patient population with long follow-up using a simple tool designed to identify subtle treatment-related side effects; and to identify clinical and technical variables associated with increased morbidity after irradiation. Methods and Materials: A total of 441 patients with nonmetastatic adenocarcinoma of the prostate treated at the Joint Center for Radiation Therapy between 1985 and 1989 were eligible for analysis. Gastrointestinal, genitourinary, and sexual function were assessed retrospectively using a patient self-scoring, five-grade toxicity scale. Seven clinical and 15 technical variables were recorded for each patient. The association between the clinical and technical variables and rectal, bladder, and sexual side effects was examined. The 375 patients who received small-field (<12.5 x 12.5-cm) external beam irradiation via a four-field box on a 6-MV (n = 74, or 20% of patients), 8-MV (n = 140, or 37%), or 15-MV (n = 161, or 43%) linear accelerator form the basis for the study. Ninety-one percent of patients received treatment with 1.8-2.0 Gy fractions to a delivered dose of at least 66 Gy. Follow-up was complete through 62 months in living patients, with five (1%) of the entire group lost to follow-up. Results: A total of 137 of 354 evaluable patients (39%) reported rectal complications after treatment; however, 20 patients(6%) had heme-positive stools as their only symptom and 66 (19%) had mild symptoms not requiring treatment. Only 14% of the entire group required intervention. Of 356 patients, 117 (33%) evaluable for bladder complications developed genitourinary changes: In 14 patients (4%) asymptomatic hematuria occurred, 71 (20%) had mild symptoms not requiring treatment, and 32 (9%) required treatment. Of the 171 patients who were potent prior to radiation, 106 (62%) reported impotence after treatment. No statistically significant association was identified between any clinical or technical variables (including machine energy) assessed and complications. Conclusions: In this retrospective review, treatment-related bowel and bladder side effects mere not identified in the majority of patients despite the use of a grading system designed to identify subtle changes. Impotence, however, was common. Although pretreatment clinical characteristics varied among patients, they could not be used to predict the subsequent development of complications. The only treatment-related characteristic that varied in this study was machine energy, which did not correlate with complications. (C) 1998 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Beard, CJ (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. NR 30 TC 33 Z9 35 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 1998 VL 41 IS 2 BP 257 EP 262 DI 10.1016/S0360-3016(98)00054-6 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA ZP346 UT WOS:000073743100003 PM 9607338 ER PT J AU Ye, HQQ Azar, DT AF Ye, HQQ Azar, DT TI Expression of gelatinases A and B, and TIMPs 1 and 2 during corneal wound healing SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID EXCIMER-LASER KERATECTOMY; MATRIX METALLOPROTEINASES; BASEMENT-MEMBRANE; TUMOR INVASION; MESSENGER-RNA; LOCALIZATION; FIBROBLASTS; METASTASIS; CARCINOMAS; INHIBITOR AB PURPOSE. To determine the expression of gelatinases A and B and the localization of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 during the early stages of corneal wound healing in rats. METHODS. One eye each of 30 adult Sprague-Dawley rats was treated with excimer laser keratectomy; the other eye was untreated. Frozen sections of corneas obtained 6, 18, and 24 hours and 5 and 7 days after wounding were used to perform immunoconfocal microscopy and in situ hybridization. RESULTS. Gelatinase B was immunolocalized to the basement membrane zone and superficial stroma, and its mRNA was exclusively localized to basal epithelial cells migrating across the wound at 18 and 24 hours and 5 days after mounding. Tissue inhibitor of metalloproteinase-1 was also immunolocalized to the basement membrane zone and superficial stroma at the same time points. Gelatinase A was immunolocalized re the epithelium and stroma of normal corneas and was predominant in the basal epithelium and superficial stroma at 3 and 7 days after wounding. In situ hybridization confirmed gelatinase A expression by the epithelial cells and the stromal keratocytes. Tissue inhibitor of metalloproteinase-2 was immunolocalized to the epithelium in normal and wounded corneas. Intense TIMP-2 labeling of the basement membrane zone was noted 3 days after wounding. CONCLUSIONS. Unlike gelatinase A, gelatinase B is expressed exclusively by migrating basal epithelial cells after wounding. The matrix metalloproteinase-tissue inhibitor of metalloproteinase (MMP)/TIMP systems map plap an important role in the early stages of corneal wound healing after excimer laser keratectomy. C1 Massachusetts Eye & Ear Infirm, Cornea Serv, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Cornea Serv, Schepens Eye Res Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY10101] NR 26 TC 130 Z9 133 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1998 VL 39 IS 6 BP 913 EP 921 PG 9 WC Ophthalmology SC Ophthalmology GA ZL068 UT WOS:000073395600008 PM 9579471 ER PT J AU Tesavibul, N Dorfman, D Sangwan, VS Christen, W Panayotis, Z Rojas, B Foster, CS AF Tesavibul, N Dorfman, D Sangwan, VS Christen, W Panayotis, Z Rojas, B Foster, CS TI Costimulatory molecules in ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID T-CELL ACTIVATION; DENDRITIC CELLS; ADDITIONAL LIGAND; LYMPHOCYTES-T; CD28; CTLA-4; EXPRESSION; ANTIGEN; B7; RECEPTOR AB Purpose. To examine normal and inflamed conjunctiva from patients with ocular cicatricial pemphigoid (OCP) for the presence of costimulatory molecule CD28 and its ligands B7-1 (CD80) and B7-2 (CD86). METHODS. Conjunctival biopsy specimens from 12 patients with OCP and from five healthy persons undergoing cataract surgery were analyzed by light microscopy and immunohistochemical examination with monoclonal antibody probes for CD28, B7-1, and B7-2 molecules and for mononuclear cell subtypes. RESULTS. Epithelium of OCP conjunctiva showed more Langerhans' cells, B7-1-positive (+) cells, and B7-2 expression (ratio of B7-2-positive cells to antigen-presenting cells). Ln the substantia propria, OCP specimens showed significantly increased numbers of T cells (CD3+), macrophages (CD68+), CD28+ cells, B7-2+ cells (CD86+), Langerhans' cells (CD1a), and B7-1+ cells (CD80). Most of the B7-2+ cells, macrophages, and Langerhans' cells were located subepithelially. B7-2 expression was significantly higher in OCP conjunctival substantia propria compared with normal conjunctiva, Conclusions. The results of this study indicate that the expression of the costimulatory molecule B7-2 is upregulated in conjunctiva of patients with active OCP. This increased subepithelial B7-2 expression may contribute to the sustained immune activation in OCP conjunctiva. C1 Massachusetts Eye & Ear Infirm, Uveitis & Immunol Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Uveitis & Immunol Serv, 243 Charles St, Boston, MA 02114 USA. OI ROJAS LOPEZ, MARIA BLANCA/0000-0002-8980-4659; Sangwan, Virender/0000-0002-8229-4158 NR 38 TC 13 Z9 15 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1998 VL 39 IS 6 BP 982 EP 988 PG 7 WC Ophthalmology SC Ophthalmology GA ZL068 UT WOS:000073395600014 PM 9579477 ER PT J AU Ayehunie, S Belay, A Baba, TW Ruprecht, RM AF Ayehunie, S Belay, A Baba, TW Ruprecht, RM TI Inhibition of HIV-1 replication by an aqueous extract of Spirulina platensis (Arthrospira platensis) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE Arthrospira platensis extract; HIV-1 replication inhibition; primary cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLUE-GREEN-ALGAE; SULFATED POLYSACCHARIDES; REVERSE-TRANSCRIPTASE; NATURAL-PRODUCTS; LANGERHANS CELLS; CALCIUM SPIRULAN; IN-VITRO; INFECTION; TANNINS AB An aqueous extract of the blue-green filamentous algae Arthrospira platensis (previously called Spirulina platensis) inhibited HIV-1 replication in human T-cell lines, peripheral blood mononuclear cells (PBMC), and Langerhans cells (LC). Extract concentrations ranging between 0.3 and 1.2 mu g/ml reduced viral production by approximately 50% (50% effective concentration [EC50]) in PBMCs. The 50% inhibitory concentration (IC50) of extract for PBMC growth ranged between 0.8 and 3.1 mg/ml. Depending on the cell type used, therapeutic indices ranged between 200 and 6000. The extract inactivated HIV-1 infectivity directly when preincubated with virus before addition to human T-cell lines. Fractionation of the extract revealed antiviral activity in the polysaccharide fraction and also in a fraction depleted of polysaccharides and tannins. We conclude that aqueous A platensis extracts contain antiretroviral activity that may be of potential clinical interest. C1 Dana Farber Canc Inst, Lab Viral Pathogenesis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Lab Viral Pathogenesis, Boston, MA 02115 USA. Earthrise Farms, Calipatria, CA USA. Tufts Univ, Sch Med, Dept Pediat, Div Newborn Med, Boston, MA 02111 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Lab Viral Pathogenesis, 44 Binney St, Boston, MA 02115 USA. NR 24 TC 67 Z9 83 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAY 1 PY 1998 VL 18 IS 1 BP 7 EP 12 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZM282 UT WOS:000073522900002 PM 9593452 ER PT J AU Garcia, AW Pender, NJ Antonakos, CL Ronis, DL AF Garcia, AW Pender, NJ Antonakos, CL Ronis, DL TI Changes in physical activity beliefs and behaviors of boys and girls across the transition to junior high school SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE physical activity; physical activity beliefs; adolescents; gender differences ID EXERCISE AB Purpose: This longitudinal study investigated gender-specific changes in physical activity beliefs and behaviors across the elementary to junior high school transition. Methods: Physical activity beliefs and behaviors were measured in a cohort of 132 racially diverse youth during the year prior to and following the transition. Questionnaires assessed variables hypothetically linked to activity. Physical activity was monitored with the Child/Adolescent Activity Log. Results: Gender differences in physical activity beliefs emerged. Across the transition, boys reported decreased efficacy, social support, and expectations (norms) to be physically active. Although girls also reported decreased social support for physical activity, they further reported exposure to fewer active role models and were less likely to perceive that the benefits of regular activity outweighed the barriers following the transition. Gender differences in activity levels were apparent, with girls being less active than boys. Despite changes in physical activity beliefs across the school transition, no significant changes in actual level of activity occurred over this period. Although beliefs were significantly related to behaviors in the domain of physical activity, pretransition activity level was the best predictor of posttransition activity level. Conclusions: These data indicate that physical activity beliefs of adolescents change over the school transition. C1 Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. Univ Michigan, Div Kinesiol, Ann Arbor, MI 48109 USA. US Dept Vet Affairs, Ann Arbor, MI USA. RP Pender, NJ (reprint author), Univ Michigan, Sch Nursing, 400 N Ingalls, Ann Arbor, MI 48109 USA. RI Loureiro, Nuno/I-6400-2012; OI Loureiro, Nuno/0000-0002-1166-3219; Antonakos, Cathy L/0000-0003-3163-9838 FU NINR NIH HHS [NR02962] NR 27 TC 78 Z9 79 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD MAY PY 1998 VL 22 IS 5 BP 394 EP 402 DI 10.1016/S1054-139X(97)00259-0 PG 9 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA ZL731 UT WOS:000073464800008 PM 9589341 ER PT J AU Cook, IA Leuchter, AF Uijtdehaage, SHJ Osato, S Holschneider, DH Abrams, M Rosenberg-Thompson, S AF Cook, IA Leuchter, AF Uijtdehaage, SHJ Osato, S Holschneider, DH Abrams, M Rosenberg-Thompson, S TI Altered cerebral energy utilization in late life depression SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE major depression; late life depression; physiology; EEG; cordance ID POSITRON EMISSION TOMOGRAPHY; BLOOD-FLOW; GLUCOSE-METABOLISM; MAJOR DEPRESSION; MOOD DISORDERS; UNIPOLAR DEPRESSION; PERFUSION; EMOTION; CORTEX; STATE AB Background: Global and regional changes in cerebral energy utilization are reported to characterize late life depression. Methods: Twenty seven subjects with late life depression (9 prior to starting medication, 18 after starting) and 27 matched controls were evaluated with cordance, a quantitative EEG measure that reflects cerebral energy utilization. Results: Global and focal (anterior and centrotemporal) differences were present in theta-band cordance between unmedicated depressed and control subjects. Depressed subjects receiving treatment had cordance patterns similar to controls. Conclusions: The presence of both diffuse and focal disturbances in energy utilization prior to initiating treatment indicates that cordance detects altered cerebral physiology in depressed patients, and that this measure may also be sensitive to treatment interventions. (C) 1998 Elsevier Science B.V. C1 Univ Calif Los Angeles, Sch Med, Neuropsychiat Inst & Hosp, Quantitat EEG Lab, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. Univ So Calif, Sch Med, Dept Psychiat, Los Angeles, CA USA. Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA USA. RP Cook, IA (reprint author), Univ Calif Los Angeles, Sch Med, Neuropsychiat Inst & Hosp, Quantitat EEG Lab, Los Angeles, CA 90024 USA. EM icook@ucla.edu OI Uijtdehaage, Sebastian/0000-0001-8598-4683 FU NIMH NIH HHS [T32-MH17140, R01-MH40705, K02-MH01165] NR 45 TC 20 Z9 20 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAY PY 1998 VL 49 IS 2 BP 89 EP 99 DI 10.1016/S0165-0327(97)00192-4 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZK956 UT WOS:000073384500001 PM 9609672 ER PT J AU Craig, TJ Teets, S Lehman, EB Chinchilli, VM Zwillich, C AF Craig, TJ Teets, S Lehman, EB Chinchilli, VM Zwillich, C TI Nasal congestion secondary to allergic rhinitis as a cause of sleep disturbance and daytime fatigue and the response to topical nasal corticosteroids SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE sleep; fatigue; rhinitis; corticosteroids; sleep disorders; sleep disturbances; nasal congestion; allergic disease ID INTRANASAL FLUTICASONE PROPIONATE; BECLOMETHASONE DIPROPIONATE; TERFENADINE TABLETS; SPRAY; FRAGMENTATION; AEROSOL; APNEA AB Background: Allergic rhinitis (AR) is a frequent disease affecting up to 20% of the population. AR causes a hypersensitivity reaction, which results in inflamed nasal mucosa and nasal congestion. Negative pressure generated during inspiration in the nasal airway secondary to nasal congestion may lead to nasal collapse, airway obstruction, and an increased number of sleep microarousals. Sleep disturbances and microarousals can detrimentally affect daytime energy levels, mood, and daytime function. It is unknown whether treatment directed to reduce congestion may reduce these microarousals, sleep problems, and, consequently, associated daytime fatigue. Objective: We sought to determine whether reducing nasal congestion with nasal steroids will reduce sleep complaints and daytime sleepiness. Method: We enrolled 20 subjects in a double-blind, placebo-controlled study using Balaam's Design. Patients were treated with topical nasal corticosteroids or placebo. Subjective data were collected by use of a daily diary, which focused on nasal symptoms, sleep, and daytime sleepiness. Results: The results demonstrated that nasal congestion and subjective sleep improved significantly in the topical corticosteroid-treated subjects but not in the placebo group. Sleepiness improved, but not significantly (p = 0.08). Conclusion: Often, people with perennial allergies may attribute their daytime fatigue to causes such as the side effects of medications, when in fact, the fatigue may be a result of nasal congestion and associated sleep fragmentation. Decreasing nasal congestion with nasal steroids may improve sleep, daytime fatigue, and the quality of Life of patients with AR. C1 Penn State Univ, Div Med, Sect Pulm Allergy & Crit Care, Allergy Clin,Dept Med, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Hershey, PA 17033 USA. Penn State Univ, Dept Hlth Evaluat Sci, Hershey, PA 17033 USA. Denver Vet Affairs Med Ctr, Med Serv, Denver, CO USA. RP Craig, TJ (reprint author), Penn State Univ, Div Med, Sect Pulm Allergy & Crit Care, Allergy Clin,Dept Med, 500 Univ Dr, Hershey, PA 17033 USA. NR 34 TC 167 Z9 170 U1 1 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 1998 VL 101 IS 5 BP 633 EP 637 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA ZN926 UT WOS:000073697400011 PM 9600500 ER PT J AU Lara-Marquez, ML Deykin, A Krinzman, S Listman, J Israel, E He, HZ Christiani, DC Perkins, DL Finn, PW AF Lara-Marquez, ML Deykin, A Krinzman, S Listman, J Israel, E He, HZ Christiani, DC Perkins, DL Finn, PW TI Analysis of T-cell activation after bronchial allergen challenge in patients with atopic asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; allergen challenge; T helper cells; CD45 R isoforms; interleukin-2R; MHC class II ID PERIPHERAL-BLOOD; BRONCHOALVEOLAR LAVAGE; CD45 ISOFORMS; AIRWAY HYPERREACTIVITY; LYMPHOCYTE SUBSETS; MEMORY; EXPRESSION; ANTIGEN; PHENOTYPE; UCHL1 AB Background: T helper cells are a heterogeneous group of cells that have phenotypic and functional differences. Activated T helper cells have been found in peripheral blood after allergen challenge of subjects with atopic asthma, but the phenotypes of specific T helper subpopulation involved remains to be identified. Objective: To characterize the T cell activation markers that may be regulated by allergens, we analyzed peripheral blood lymphocytes obtained before and after allergen challenge from subjects with atopic asthma. Methods: We analyzed the distribution of the cell surface activation markers, interleukin 2 receptor (IL-2R) and major histocompatibility complex class Ii antigens (MHC II) among T helper subpopulations classified as naive (CD45RA) or memory (CD45RO) phenotypes. Nine adult subjects with atopic asthma underwent bronchoprovacative allergen inhalation and isocapnic cold air hyperventilation (ISH) challenge followed by serial spirometry. Peripheral blood mononuclear cells (PBMC) were isolated at baseline and 2 and 24 hours after challenge. Four color how cytometry was used to analyze the expression and distribution in vivo of IL-2R and MHC LI activation markers on naive and memory T cell subsets after challenge. Results: At 2 and 24 hours after allergen challenge, there was a significant increase in the CD45RO+IL-2R+ T helper cells compared with baseline (mean +/- SE, baseline, 12.5% +/- 1% versus 2 hours, 18.1% +/- 1% and 24 hours, 17.8% +/- 2%, p < 0.025). MHC II expression was not significantly increased after challenge on naive and memory T helper cells and coexpression of IL-PR and MHC II was only found in a small proportion of CD45RO+ T helper cells (2.7% +/- 1%). No changes of IL-2R or MBC II expression on T helper subsets were observed after ISH challenge in the same patients. We also found that 31% to 46% of T helper cells coexpress CD45RA and CD45RO simultaneously, and upregulation of IL-2-R and MHC II expression occurs only on those T helper cells that express CD45RO. Conclusions: We have found that T helper cells express both CD45RA and CD45RO isoforms, which suggests the existence of a transitional phenotype among naive and memory T helper cells in peripheral blood. In subjects with atopic asthma, our in vivo analysis characterizes two populations of activated memory T helper cells based on the expression of IL-2R or MHC II surface molecules after allergen challenge. C1 Brigham & Womens Hosp, Div Resp, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. Beth Israel Hosp, Div Resp, Boston, MA USA. Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Finn, PW (reprint author), Brigham & Womens Hosp, Div Resp, 75 Francis St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI33100]; NIEHS NIH HHS [ES00002, ES06568] NR 41 TC 26 Z9 26 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 1998 VL 101 IS 5 BP 699 EP 708 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA ZN926 UT WOS:000073697400020 PM 9600509 ER PT J AU Otto, MW Demopulos, CM McLean, NE Pollack, MH Fava, M AF Otto, MW Demopulos, CM McLean, NE Pollack, MH Fava, M TI Additional findings on the association between anxiety sensitivity and hypochondriacal concerns: Examination of patients with major depression SO JOURNAL OF ANXIETY DISORDERS LA English DT Article ID DSM-III HYPOCHONDRIASIS; PANIC DISORDER; BELIEFS; FEARS; OUTPATIENTS; ATTITUDES AB Hypochondriacal concerns ranging from disease phobias to bodily preoccupations are common among patients with panic disorder. In a previous study of patients with panic disorder, we found that, of a number of symptom dimensions examined, anxiety sensitivity was the strongest predictor of hypochondriacal concerns. This finding has been the topic of subsequent debate in the anxiety literature, with concerns raised whether true hypochondriacal concerns were confounded with typical panic-related concerns. To clarify this issue, we now report on the association between anxiety sensitivity and hypochondriacal concerns in 100 patients with major depression and no history of panic disorder. Consistent with our previous study, we found that of the symptoms examined-anxiety sensitivity, depressed mood, anxious mood, somatic symptoms, and anger/hostility -anxiety sensitivity was the strongest predictor of hypochondriacal concerns. Findings are discussed in relation to the role of catastrophic interpretations of somatic symptoms in depression, panic disorder, and hypochondriasis. (C) 1998 Elsevier Science Ltd. C1 Massachusetts Gen Hosp, Cognit Behav Therapy Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Cognit Behav Therapy Program, WACC-815,15 Parkman St, Boston, MA 02114 USA. NR 30 TC 41 Z9 41 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD MAY-JUN PY 1998 VL 12 IS 3 BP 225 EP 232 DI 10.1016/S0887-6185(98)00011-5 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZW156 UT WOS:000074380700005 PM 9653681 ER PT J AU Perell, KL Gregor, RJ Scremin, AME AF Perell, KL Gregor, RJ Scremin, AME TI Lower limb cycling mechanics in subjects with unilateral cerebrovascular accidents SO JOURNAL OF APPLIED BIOMECHANICS LA English DT Article DE hemiplegia; biomechanics; cerebral vascular disorders; asymmetry ID STROKE PATIENTS; POSTURAL STABILITY; HEMIPLEGIC GAIT; JOINT ANGLE; PERFORMANCE; HEMIPARESIS; LOCOMOTION; ERGOMETER; FEEDBACK; REHABILITATION AB Biomechanical analysis of the generalized muscle moment and pourer patterns involved in cycling provides information regarding coordination within each limb. The purpose of this study was to compare individual joint kinetics, bilaterally, in subjects who had experienced cerebrovascular accidents (CVAs). Two-dimensional cinematography and force pedal data in a linked-segment model were used to study 8 ambulatory subjects while they rode a recumbent bicycle. The involved lower limb was defined as the lower limb with the greatest deficits, whereas the contralateral lower limb was defined as the lower limb opposite the involved lower Limb and ipsilateral to the lesion site. The contralateral lower limbs of subjects with CVAs demonstrated patterns similar to those reported for nondisabled cyclists on an upright bicycle except for a bimodal hip power generation pattern that was possibly due to compensation for a lack of involved lower limb power generation. There were two critical findings of this study: Single-joint power generation patterns during the power phase indicated that either the hip or the knee, bur not both joints, generated power in the involved lower limb, and asymmetrical differences between lower limbs appeared significant at the ankle alone. C1 W Los Angeles Vet Affairs Med Ctr, Dept Phys Med & Rehabil Serv, Los Angeles, CA 90073 USA. Mt St Marys Coll, Dept Phys Therapy, Los Angeles, CA 90049 USA. Georgia Inst Technol, Dept Hlth & Performance Sci, Atlanta, GA 30332 USA. Univ Calif Los Angeles, Sch Med, Dept Med, PM&R Div, Los Angeles, CA 90024 USA. RP Perell, KL (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Phys Med & Rehabil Serv, PM&R 117, Los Angeles, CA 90073 USA. NR 35 TC 15 Z9 15 U1 0 U2 2 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1065-8483 J9 J APPL BIOMECH JI J. Appl. Biomech. PD MAY PY 1998 VL 14 IS 2 BP 158 EP 179 PG 22 WC Engineering, Biomedical; Sport Sciences SC Engineering; Sport Sciences GA ZL280 UT WOS:000073416800003 ER PT J AU Johnstone, RW Wang, J Tommerup, N Vissing, H Roberts, T Shi, Y AF Johnstone, RW Wang, J Tommerup, N Vissing, H Roberts, T Shi, Y TI Ciao 1 is a novel WD40 protein that interacts with the tumor suppressor protein WT1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WILMS-TUMOR; GENE-PRODUCT; TRANSCRIPTIONAL REPRESSION; FUNCTIONAL INTERACTION; NUCLEAR-LOCALIZATION; GROWTH SUPPRESSION; WD-40 REPEAT; DOMAINS; CLONING; COMPLEX AB The Wilms tumor suppressor protein, WT1, is a transcription factor capable of activating or repressing transcription of various cellular genes. The mechanisms involved in regulating the transcriptional activities of WT1 are beginning to be unraveled. It appears that physical interactions of other cellular proteins (p53 and par-4) with WT1 can modulate the function of WT1. Here, we report the identification and cloning of a novel WT1-interacting protein termed Ciao 1, a member of the WD40 family of proteins. Ciao 1 specifically interacts with WT1 both in vitro and in vivo. This interaction alters the mobility of a WT1 DNA complex in gel shift assays, and results in a decrease in transcriptional activation mediated by WT1, Ciao 1 does not inhibit binding of WT1 to its consensus nucleotide sequence and does not affect the repression activity of WT1. Thus, Ciao 1 appears to specifically modulate the transactivation activity of WT1 and may function to regulate the physiological functions of WT1 in cell growth and differentiation. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. Univ Copenhagen, Panum Inst, Dept Med Genet, DK-2200 Copenhagen, Denmark. Novo Nordisk AS, Mol Genet, DK-2880 Bagsvaerd, Denmark. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. EM yshi@warren.med.harvard.edu FU NCI NIH HHS [R01 CA 68258] NR 60 TC 51 Z9 53 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 1 PY 1998 VL 273 IS 18 BP 10880 EP 10887 DI 10.1074/jbc.273.18.10880 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL064 UT WOS:000073395200015 PM 9556563 ER PT J AU Foertsch, CE O'Hara, MW Stoddard, FT Kealey, GP AF Foertsch, CE O'Hara, MW Stoddard, FT Kealey, GP TI Treatment-resistant pain and distress during pediatric burn-dressing changes SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID BEHAVIORAL DISTRESS; CHILDRENS DISTRESS; MEDICAL PROCEDURES; HYPNOSIS; CANCER; REDUCTION; ADOLESCENTS; ANXIETY; DEBRIDEMENT; MANAGEMENT AB Recent research has suggested some efficacy for the use of hypnosis in the control of pain and distress in a pediatric population undergoing painful medical procedures. Here, we study a sample (N = 23) of pediatric subjects undergoing burn-dressing changes and receiving either an imagery-based or control (social-support) treatment. Subjects' levels of distress were assessed with the Observational Scale of Behavioral Distress. Results indicated that distress behaviors in this population can be measured reliably using this scale. However, no support was found for the main hypothesis that imagery treatment would be superior to control treatment in the alleviation of distress, nor were these treatments effective in comparison to baseline conditions. We discuss the formidable problem that burn and dressing-change pain presents, as well as the reasons why this treatment attempt might have failed to have the predicted effects. We also discuss important developmental considerations regarding the adequate assessment of pain and distress. C1 New York Hosp, Cornell Med Ctr, Westchester Div, Dept Psychol Macy Villa, White Plains, NY 10605 USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Univ Iowa Hosp & Clin, Burn Treatment Ctr, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Foertsch, CE (reprint author), New York Hosp, Cornell Med Ctr, Westchester Div, Dept Psychol Macy Villa, 21 Bloomingdale Rd, White Plains, NY 10605 USA. NR 23 TC 21 Z9 22 U1 2 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD MAY-JUN PY 1998 VL 19 IS 3 BP 219 EP 224 DI 10.1097/00004630-199805000-00007 PG 6 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 115UY UT WOS:000075685300006 PM 9622466 ER PT J AU McDonald-Smith, GP AF McDonald-Smith, GP TI Descriptive statistics: Practical applications of the NATIONAL TRACS (R) ABA Burn Registry SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article C1 Massachusetts Gen Hosp, Trauma & Burn Serv, Boston, MA 02114 USA. RP McDonald-Smith, GP (reprint author), Massachusetts Gen Hosp, Trauma & Burn Serv, GRB 1302, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD MAY-JUN PY 1998 VL 19 IS 3 BP 261 EP 264 PG 4 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 115UY UT WOS:000075685300016 PM 9622473 ER PT J AU Katznelson, L Bogan, JS Trob, JR Schoenfeld, DA Hedley-Whyte, ET Hsu, DW Zervas, NT Swearingen, B Sleeper, M Klibanski, A AF Katznelson, L Bogan, JS Trob, JR Schoenfeld, DA Hedley-Whyte, ET Hsu, DW Zervas, NT Swearingen, B Sleeper, M Klibanski, A TI Biochemical assessment of Cushing's disease in patients with corticotroph macroadenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MONOCLONAL-ANTIBODY KI-67; PITUITARY-ADENOMAS; GLUCOCORTICOID-RECEPTOR; DIFFERENTIAL-DIAGNOSIS; MANAGEMENT; MUTATION; CORTISOL AB The majority of cases of Cushing's disease are due to an underlying pituitary corticotroph microadenoma (less than or equal to 10 mm). Corticotroph macroadenomas (>10 mm) are a less common cause of Cushing's disease, and little is known about specific clinical and biochemical findings in such patients. To define further the clinical characteristics of patients with corticotroph macroadenomas, we performed a retrospective review of Cushing's disease due to macroadenomas seen at Massachusetts General Hospital between 1979 and 1995. Of 531 patients identified with a diagnostic code of Cushing's syndrome, 20 were determined to have Cushing's disease due to a macroadenoma based on radiographic evidence of pituitary adenoma greater than 10 mm and pathological confirmation of a pituitary adenoma. A comparison review of charts of 24 patients with Cushing's disease due to corticotroph microadenomas identified on the basis of radiographic evidence of a normal pituitary gland or a pituitary adenoma 10 mm or less in diameter was also performed. The mean ages of the patients (+/-SD) with macroadenomas and microadenomas were similar (39 +/- 12 and 38 +/- 14 yr, respectively). The baseline median 24-h urine free cortisol (UFC) excretion was 1341 nmol/day (range, 304-69,033 nmol/day) and 877 nmol/day (range, 293-2,558 nmol/day) for macroadenoma and microadenoma patients, respectively (P = 0.058). After the 48-h high dose dexamethasone suppression test, UFC decreased by 77 +/- 19% (mean +/-SD) and 91 +/- 7% in macroadenoma and microadenoma subjects, respectively (P = 0.04). Fifty-six percent of macroadenoma patients and 92% of microadenoma patients had greater than 80% suppression of UFC after high dose dexamethasone administration (P = 0.03). The baseline median 24-h urinary 17-hydroxysteroid (17-OHGS) excretion was 52 mu mol/day (range, 25-786 mu mol/day) and 44 mu mol/day (range, 17-86 mu mol/day) for macroadenoma and microadenoma subjects, respectively (P = 0.09). After the standard high dose dexamethasone suppression test, 17-OHCS excretion decreased by 46 +/- 33% and 72 +/- 22% for macroadenoma and microadenoma subjects, respectively (P = 0.02). Fifty-three percent of patients with macroadenomas and 86% of patients with microadenomas had greater than 50% suppression of 17-OHCS after high dose dexamethasone administration (P = 0.02). Baseline plasma ACTH values were above the normal range in 83.3% of macroadenoma patients and in 45% of microadenoma subjects (P = 0.05). Tumors were immunostained with the MIB-1 antibody for Ki-67 to investigate proliferation in the adenomas. There was a trend for a higher Ki-67 labeling index in corticotroph macroadenomas, and seven (44%) macroadenomas vs three (18%) microadenomas had labeling indexes greater than 3%, but this was not statistically significant. In summary, corticotroph macroadenomas are often associated with less glucocorticoid suppressibility than the more frequently occurring microadenomas. Therefore, the lack of suppression of UFC or 17-OHCS after the administration of high dose dexamethasone in a patient with Cushing's disease does not necessarily imply the presence of ACTH-independent Cushing's syndrome and is more commonly seen in patients with corticotroph macroadenomas than in those with microadenomas. Increased plasma ACTH concentrations are typical of patients with corticotroph macroadenomas and may be a more sensitive indicator of neoplastic corticotrophs than the UFC or 17-OHCS response to standard high dose dexamethasone testing. C1 Massachusetts Gen Hosp, Neuroendocrinol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Endocrine, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Katznelson, L (reprint author), Massachusetts Gen Hosp, Neuroendocrinol Unit, Bullfinch 457,32 Fruit St, Boston, MA 02114 USA. RI Bogan, Jonathan/A-1575-2010 OI Bogan, Jonathan/0000-0001-6463-8466 FU NCRR NIH HHS [M01-RR-01066] NR 22 TC 53 Z9 57 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1998 VL 83 IS 5 BP 1619 EP 1623 DI 10.1210/jc.83.5.1619 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZM396 UT WOS:000073535300039 PM 9589666 ER PT J AU Palanisamy, N Imanishi, Y Rao, PH Tahara, H Chaganti, RSK Arnold, A AF Palanisamy, N Imanishi, Y Rao, PH Tahara, H Chaganti, RSK Arnold, A TI Novel chromosomal abnormalities identified by comparative genomic hybridization in parathyroid adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TUMOR-SUPPRESSOR GENE; DNA; RETINOBLASTOMA; LOSSES; CANCER; GAINS; NEOPLASIA; ONCOGENE; LOCI AB The molecular basis of parathyroid adenomatosis includes defects in the cyclin D1/PRAD1 and MEN1 genes but is, in large part, unknown. To identify new locations of parathyroid oncogenes or tumor suppressor genes, and to further establish the importance of DNA losses described by molecular allelotyping, we performed comparative genomic hybridization (CGH) on a panel of 53 typical sporadic (nonfamilial) parathyroid adenomas. CGH is a new molecular cytogenetic technique in which the entire tumor genome is screened for chromosomal gains and/or losses. Two abnormalities, not previously described, were found recurrently: gain of chromosome 16p (6 of 53 tumors, or 11%) and gain of chromosome 19p (5 of 53, or 9%). Losses were found frequently on 11p (14 of 53, or 26%), as well as 11q (18 of 53, or 34%). Recurrent losses were also seen on chromosomes 1p, 1q, 6q, 9p, 9q, 13q, and 15q, with frequencies ranging from 8-19%. Twenty-four of the 53 adenomas were also extensively analyzed with polymorphic microsatellite markers for allelic losses, either in this study (11 cases) or previously (13 cases). Molecular allelotyping results were highly concordant with CGH results in these tumors (concordance level of 97.5% for all informative markers/chromosome arms examined). In conclusion, CGH has identified the first two known chromosomal gain defects in parathyroid adenomas, suggesting the existence of direct-acting parathyroid oncogenes on chromosomes 16 and 19. CGH has confirmed the locations of putative parathyroid tumor suppressor genes, also defined by molecular allelotyping, on chromosomes 1p, 6q, 9p, 11q, 13q, and 15q. Finally, CGH has provided new evidence favoring the possibility that distinct parathyroid tumor suppressors exist on 1p and 1q, and has raised the possibility of a parathyroid tumor suppressor gene on 11p, distinct from the MEN1 gene on 11q. CGH can identify recurrent genetic abnormalities in hyperparathyroidism, especially chromosomal gains, that other methods do not detect. C1 Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA. Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA. Massachusetts Gen Hosp, Lab Endocrine Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Arnold, A (reprint author), Univ Connecticut, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. OI Palanisamy, Nallasivam/0000-0002-0633-9772 FU NIDDK NIH HHS [DK-11794] NR 19 TC 99 Z9 99 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1998 VL 83 IS 5 BP 1766 EP 1770 DI 10.1210/jc.83.5.1766 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZM396 UT WOS:000073535300063 PM 9589690 ER PT J AU Gewirtz, AT McCormick, B Neish, AS Petasis, NA Gronert, K Serhan, CN Madara, JL AF Gewirtz, AT McCormick, B Neish, AS Petasis, NA Gronert, K Serhan, CN Madara, JL TI Pathogen-induced chemokine secretion from model intestinal epithelium is inhibited by lipoxin A(4) analogs SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE IL-8; Salmonella; neutrophil; transmigration; inflammation; chemokine ID HUMAN-NEUTROPHILS; SALMONELLA-TYPHIMURIUM; CELLS; TRANSMIGRATION; ATTACHMENT; MONOLAYERS; INTERLEUKIN-8; ACTIVATION; EXPRESSION; INVASION AB Enteric pathogens induce intestinal epithelium to secrete chemokines that direct movement of polymorphonuclear leukocytes. Mechanisms that might downregulate secretion of these proinflammatory chemokines and thus contain intestinal inflammation have not yet been elucidated. The antiinflammatory activities exhibited by the arachidonate metabolite lipoxin A(4) (LXA(4)) suggests that this eicosanoid, which is biosynthesized in vivo at sites of inflammation, might play such a role. We investigated whether chemokine secretion could be regulated by stable analogs of LXA(4). Monolayers of T84 intestinal epithelial cells were infected with Salmonella typhimurium, which elicits secretion of distinct apical (pathogen-elicited epithelial chemoattractant) and basolateral (IL-8) chemokines. Stable analogs of LXA(4) inhibited S. typhimurium-induced (but not phorbol ester-induced) secretion of both IL-8 and pathogen-elicited epithelial chemoattractant. LXA(4) stable analogs did not alter bacterial adherence to nor internalization by epithelia, indicating that LXA(4) stable analogs did not block all signals that Salmonella typhimurium activates in intestinal epithelia, but likely led to attenuation of signals that mediate chemokine secretion. Inhibition of S. typhimurium-induced IL-8 secretion by LXA(4) analogs was concentration-(IC50 similar to 1 nM) and time-dependent (maximal inhibition similar to 1 h). As a result of these effects, LXA(4) stable analogs inhibited the ability of bacteria-infected epithelia to direct polymorphonuclear leukocyte movement. These data suggest that LXA(4) and its stable analogs may be useful in downregulating active inflammation at mucosal surfaces. C1 Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. RP Gewirtz, AT (reprint author), Emory Univ Hosp, Dept Pathol & Lab Med, WMRB 2315, Atlanta, GA 30322 USA. EM agewirt@emory.edu RI Neish, Andrew/B-3895-2009 FU NIDDK NIH HHS [DK-35932, DK-47662, DK-50989] NR 34 TC 115 Z9 121 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1998 VL 101 IS 9 BP 1860 EP 1869 DI 10.1172/JCI1339 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZN286 UT WOS:000073630700008 PM 9576749 ER PT J AU Kitayama, J Mackay, CR Ponath, PD Springer, TA AF Kitayama, J Mackay, CR Ponath, PD Springer, TA TI The C-C chemokine receptor CCR3 participates in stimulation of eosinophil arrest on inflammatory endothelium in shear flow SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE endothelium; eosinophils; eotaxin; chemokine receptor; very late antigen 4 ID PLATELET-ACTIVATING-FACTOR; CELL-ADHESION MOLECULE-1; LEUKOCYTE ADHESION; VASCULAR ENDOTHELIUM; INTERCELLULAR-ADHESION; ALLERGIC INFLAMMATION; NEUTROPHIL ADHERENCE; PHYSIOLOGICAL FLOW; EOTAXIN RECEPTOR; T-LYMPHOCYTES AB Chemokines are widely hypothesized to stimulate firm adhesion of leukocytes on endothelium in shear flow. Thus far, this has been demonstrated experimentally for exogenously added chemoattractants, but not for those released by endothelium. We found that human umbilical cord endothelial cells (HUVEC) stimulated with TNF-alpha and IFN-gamma secreted eosinophil chemoattractants into the culture supernatant. This material induced transendothelial chemotaxis, stimulated eosinophil binding to purified intercellular adhesion molecule 1, and augmented binding to purified vascular cell adhesion molecule 1 in a 3-min static assay. Chemotaxis and stimulation of adhesion were abrogated completely by the pretreatment of eosinophils with an mAb to the C-C chemokine receptor 3 (CCR3). Eosinophils accumulated efficiently on HUVEC stimulated with TNF-alpha and IFN-gamma in shear flow at 1.5 dyn/cm(2). CCR3 mAb slightly but significantly reduced eosinophil arrest and accumulation, by preventing development of firm adhesion by some of the tethered eosinophils, so that they detached within 30 s after the initial tethering. In the presence of mAb to the alpha 4 integrin subunit, the effect of CCR3 mAb was more prominent, and approximately half of eosinophil arrest and accumulation was abolished. Inhibition by CCR3 mAb in the presence of beta 2 integrin mAb was similar to that in control eosinophils. This is the first evidence that endothelial cell-derived chemokines can activate firm adhesion through alpha 4 and beta 2 integrins even in the presence of shear flow. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. LeukoSite Inc, Cambridge, MA 02142 USA. RP Springer, TA (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. EM springer@sprsgi.med.harvard.edu RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 FU NHLBI NIH HHS [HL-48675] NR 66 TC 73 Z9 76 U1 1 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1998 VL 101 IS 9 BP 2017 EP 2024 DI 10.1172/JCI2688 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZN286 UT WOS:000073630700026 PM 9576767 ER PT J AU Kirkpatrick, WR McAtee, RK Revankar, SG Fothergill, AW McCarthy, DI Rinaldi, MG Patterson, TF AF Kirkpatrick, WR McAtee, RK Revankar, SG Fothergill, AW McCarthy, DI Rinaldi, MG Patterson, TF TI Comparative evaluation of National Committee for Clinical Laboratory Standards broth macrodilution and agar dilution screening methods for testing fluconazole susceptibility of Cryptococcus neoformans SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VITRO ANTIFUNGAL SUSCEPTIBILITY; CANDIDA-ALBICANS; AMPHOTERICIN-B; CHROMOGENIC AGAR; MENINGITIS; YEASTS AB A simple screening method for fluconazole susceptibility of Cryptococcus neoformans using 2% dextrose Sabouraud dextrose agar (SabDex) with fluconazole was compared to the National Committee for Clinical Laboratory Standards (NCCLS) broth macrodilution method. By this method, fluconazole-susceptible C. neoformans isolates are significantly smaller on medium dth fluconazole than on fluconazole-free medium. Isolates with decreased susceptibility hale normal-size colonies on medium containing fuconazole. The 48-h NCCLS broth macrodilution MICs (NCCLS MICs) for isolates with normal-size colonies on 8- or 16-mu g/ml fluconazole plates were predicted to be greater than or equal to 8 or greater than or equal to 16-mu g/ml, respectively. On medium with 16 mu g of fluconazole per ml, all strains (84 of 84) for which the NCCLS MICs were <16 mu g/ml were correctly predicted, as were all isolates (7 of 7) for which the MICs were greater than or equal to 16 mu g/ml. Agar dilution appears to he an effective screening method for fluconazole resistance in C. neoformans. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Patterson, TF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM PATTERSON@UTHSCSA.EDU FU NCRR NIH HHS [M01-RR-01346, M01 RR001346]; NIDCR NIH HHS [R01 DE011381, 5 R01-DE11381] NR 22 TC 13 Z9 14 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1998 VL 36 IS 5 BP 1330 EP 1332 PG 3 WC Microbiology SC Microbiology GA ZJ084 UT WOS:000073177900030 PM 9574699 ER PT J AU Lorensen, M Jones, DE Hamilton, GA AF Lorensen, M Jones, DE Hamilton, GA TI Advanced practice nursing in the Nordic countries SO JOURNAL OF CLINICAL NURSING LA English DT Article DE advanced clinical practice; clinical decision making; graduate nursing education; nursing education in Nordic countries; patient phenomena; role theory AB Changes in the delivery of health care and changes in population characteristics and health care requirements mandate changing requirements in nursing education. This is necessary to meet patient and family needs and to deliver quality health care. This paper describes the background to nursing education in the Nordic countries and gives an account of an initiative in Norway to prepare advanced practice nurses for clinical practice in this dynamic environment. C1 Univ Oslo, Inst Nursing Sci, N-0317 Oslo, Norway. Boston Coll, Sch Nursing, Chestnut Hill, MA 02167 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lorensen, M (reprint author), Univ Oslo, Inst Nursing Sci, POB 1120, N-0317 Oslo, Norway. NR 34 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0962-1067 J9 J CLIN NURS JI J. Clin. Nurs. PD MAY PY 1998 VL 7 IS 3 BP 257 EP 264 DI 10.1046/j.1365-2702.1998.00186.x PG 8 WC Nursing SC Nursing GA ZP005 UT WOS:000073705800010 PM 9661389 ER PT J AU Garber, J AF Garber, J TI Inherited breast cancer: Increasingly familiar territory SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Garber, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 10 TC 4 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1998 VL 16 IS 5 BP 1639 EP 1641 PG 3 WC Oncology SC Oncology GA ZL271 UT WOS:000073415900001 PM 9586872 ER PT J AU Falkson, G Gelman, RS Pandya, KJ Osborne, CK Tormey, D Cummings, FJ Sledge, GW Abeloff, MD AF Falkson, G Gelman, RS Pandya, KJ Osborne, CK Tormey, D Cummings, FJ Sledge, GW Abeloff, MD TI Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONTINUOUS CHEMOTHERAPY; WOMEN; TERM AB Purpose: To investigate the value of maintenance treatment for patients with metastatic breast cancer whose disease is in complete remission (CR). Patients and Methods: One hundred ninety-five women (141 eligible) whose disease was in CR or in CR except for bone metastases following six cycles (6 months) of doxorubicin-containing induction treatment were randomized to receive cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and halotestin [CMF(P)TH] or observation. In a previous pilot study, patients in CR after 24 months of induction treatment were randomized to continue chemotherapy for 4 more years or stop chemotherapy. Results: Among patients randomized to CMF(P)TH, life-threatening toxicity included leukopenia in 3%, thrombocytopenia in 3%, cardiac in 2%, and diabetes in 1%, The median time to relapse from randomization was 18.7 months on CMF(P)TH and only 7.8 months on observation (P < .0001), The median time to death was 32.2 months on CMF(P)TH and 28.7 months on observation (P = .74), Similar results were seen in the pilot study (median time to relapse, 12.6 and 6.4 months; median survival, 37.7 and 24.2 months; study too small for statistical significance). Maintenance treatment wets always the most significant covariate in time-to-relapse models. Conclusion: There is definite toxicity associated with CMF(P)TH maintenance treatment, When CR was obtained on induction, maintenance treatment with CMF(P)TH was never significant in survival models. However, maintenance treatment was always the most significant covariate in the time-to-relapse models, which motivates its consideration for appropriately informed patients. (C) 1998 by American Society of Clinical Oncology. C1 Univ Pretoria, Dept Med Oncol, ZA-0001 Pretoria, South Africa. St Marys Hosp, Rochester, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, Houston, TX USA. AMC Canc Res Ctr, Denver, CO USA. Roger Williams Gen Hosp, Providence, RI 02908 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. RP Falkson, G (reprint author), Univ Pretoria, Dept Med Oncol, POB 667, ZA-0001 Pretoria, South Africa. EM gfalkson@medic.up.ac.za FU NCI NIH HHS [CA 21692, CA 21076, CA 23318] NR 16 TC 59 Z9 62 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1998 VL 16 IS 5 BP 1669 EP 1676 PG 8 WC Oncology SC Oncology GA ZL271 UT WOS:000073415900006 PM 9586877 ER PT J AU Falkson, CI Ibrahim, J Kirkwood, JM Coates, AS Atkins, MB Blum, RH AF Falkson, CI Ibrahim, J Kirkwood, JM Coates, AS Atkins, MB Blum, RH TI Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2b versus dacarbazine with tamoxifen versus dacarbazine with interferon alpha-2b and tamoxifen in patients with metastatic malignant melanoma: An Eastern Cooperative Oncology Group study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMBINATION CHEMOTHERAPY; RECOMBINANT INTERFERON; RANDOMIZED TRIAL; FOTEMUSTINE; EXPERIENCE; CARMUSTINE; CISPLATIN; THERAPY; CCNU AB Purpose: To investigate the response rate, time to treatment failure (TTF), overall survival, and toxicity in patients with metastatic melanoma treated with dacarbazine alone, dacarbazine plus interferon (IFN), dacarbazine plus tamoxifen (TMX), or dacarbazine plus IFN plus TMX. Materials and Methods: Two hundred seventy-one patients (258 were eligible) were randomized in a 2 x 2 factorial design to receive one of the above treatments. The trial wets designed to detect a 50% improvement in survival with 83% power. Results: Nine complete (CRs) and 18 partial responses (PRs) were observed in the patients who received treatments that contained IFN compared with four CRs and 18 PRs in the patients who received treatments that did not contain IFN. Five CRs and 20 PRs occurred in patients treated with TMX compared with eight CRs and 16 PRs in those treated without TMX. Response differences were nonsignificant. The overall median TTF was 2.6 months, and the overall median survival wets 8.9 months. There was no significant difference in TTF or survival among any of the different treatments. Poor performance status (PS), hepatic metastases, and weight loss were significant adverse prognostic factors. Twenty-three patients had a TTF greater than 20 months, and these durable responses were evenly distributed among the treatment arms, Significantly more severe and life-threatening toxic events occurred with treatments that contained IFN. Conclusion: Neither IFN, TMX, nor the combination significantly improved the response rate, TTF, or survival when added to dacarbazine, but IFN significantly increased toxicity. (C) 1998 by American Society of Clinical Oncology. C1 Univ Pretoria, Fac Med, ZA-0001 Pretoria, South Africa. Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia. Tufts New England Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. St Vincents Comprehens Canc Ctr, New York, NY USA. RP Falkson, CI (reprint author), Univ Pretoria, Fac Med, POB 667, ZA-0001 Pretoria, South Africa. FU NCI NIH HHS [CA 07190, CA 21692, CA 23318] NR 41 TC 205 Z9 211 U1 1 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1998 VL 16 IS 5 BP 1743 EP 1751 PG 9 WC Oncology SC Oncology GA ZL271 UT WOS:000073415900016 PM 9586887 ER PT J AU Serafini, AN Klein, JL Wolff, BG Baum, R Chetanneau, A Pecking, A Fischman, AJ Wynant, GE Subramanian, R Goroff, DK Hanna, MG AF Serafini, AN Klein, JL Wolff, BG Baum, R Chetanneau, A Pecking, A Fischman, AJ Wynant, GE Subramanian, R Goroff, DK Hanna, MG TI Radioimmunoscintigraphy of recurrent, metastatic, or occult colorectal cancer with technetium 99m-labeled totally human monoclonal antibody 88BV59: Results of pivotal, phase III multicenter studies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CARCINOMA; IMMUNOSCINTIGRAPHY; MANAGEMENT; INTERFERENCE; SURGERY; TRIAL; CT AB Purpose: To assess the performance and potential clinical impact of a totally human monoclonal antibody, 88BV59 (HumaSPECT) (INTRACEL, Corp, Rockville, MD), in 202 assessable presurgical patients with recurrent, metastatic, or occult colorectal cancer. Methods: 88BV59, labeled with technetium Tc 99m (Tc-99m) (HumaSPECT-Tc), was injected intravenously, and planar and single photon emission tomography (SPECT) images were obtained 14 to 20 hours postinjection. Surgical and pathologic verification of tumor were used as the standard against which the performance of HumaSPECT-Tc imaging and computed tomography (CT) analysis were evaluated. Results: All patients entered onto the recurrent disease study had at least one tumor site defined on CT. The sensitivity of HumaSPECT-Tc in those CT-positive patients was 87%, The specificity of HumaSPECT-Tc was 57% compared with 17% for CT and the difference was statistically significant (P < .001). The diagnostic information provided by HumaSPECT-Tc significantly (P < .001) improved the accuracy of the identification of resectable and nonresectable disease over that of CT (80% v 62%). HumaSPECT-Tc scans resulted in a significant (P < .001) reduction versus CT in terms of the proportion of patients understaged (27% v 41%) and overstaged (4% v 26%). In patients with occult disease (increasing carcinoembryonic antigen [CEA] titer, negative diagnostic work-up, negative CT), HumaSPECT-Tc correctly identified disease in 15 of 22 (68%) patients. HumaSPECT-Tc images provided additional clinical data that would have affected patient management decisions in 40 of 202 (19.8%) patients. In 365 patients who received 88BV59, only a single detectable human antihuman antibody (HAHA) response (90 ng/mL) at 9 weeks postinfusion was observed. Conclusion: HumaSPECT-Tc can provide important and accurate information about the presence and location of disease in patients with a high clinical suspicion of metastatic or recurrent colorectal cancer and either positive (known disease) or negative (occult disease) CT scans. (C) 1998 by American Society of Clinical Oncology. C1 Intracel Corp, Rockville, MD 20850 USA. Univ Miami, Sch Med, Div Nucl Med, Miami, FL USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Frankfurt, Med Ctr, Dept Nucl Med, Frankfurt, Germany. Site Hosp Nord Nantes, Ctr Rene Gauducheau Ctr Reg Lutte Contre Canc, St Herblain, France. Ctr Rene Huguenin, Nucl Med Serv, St Cloud, France. RP Hanna, MG (reprint author), Intracel Corp, 1330 Piccard Dr, Rockville, MD 20850 USA. NR 24 TC 17 Z9 17 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1998 VL 16 IS 5 BP 1777 EP 1787 PG 11 WC Oncology SC Oncology GA ZL271 UT WOS:000073415900020 PM 9586891 ER PT J AU Amatruda, JF Tran, K Mantel, M Singer, S Demetri, G AF Amatruda, JF Tran, K Mantel, M Singer, S Demetri, G TI Askin tumor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SMALL CELL TUMOR; THORACOPULMONARY REGION; ENTITY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Amatruda, JF (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1998 VL 16 IS 5 BP 1997 EP 1998 PG 2 WC Oncology SC Oncology GA ZL271 UT WOS:000073415900049 PM 9586920 ER PT J AU Haffajee, AD Cugini, MA Tanner, A Pollack, RP Smith, C Kent, RL Socransky, SS AF Haffajee, AD Cugini, MA Tanner, A Pollack, RP Smith, C Kent, RL Socransky, SS TI Subgingival microbiota in healthy, well-maintained elder and periodontitis subjects SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE microbiology; bacteria; subgingival plaque; disease status; periodontal disease; periodontitis; periodontal ID ACTINOMYCETEMCOMITANS-ASSOCIATED PERIODONTITIS; PORPHYROMONAS-GINGIVALIS; TREPONEMA-DENTICOLA; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; EPITHELIAL-CELLS; DISEASE; PLAQUE; PREVALENCE; BACTERIA AB This investigation compared the site prevalence of 40 subgingival species in 30 periodontally healthy (mean age 36+/-9 years), 35 elders with a well-maintained periodontium (mean age 77+/-5) and 138 adult periodontitis subjects (mean age 46+/-11). Subgingival plaque samples were taken from the mesial aspect of each tooth (up to 28 samples) in the 203 subjects at baseline. The presence and levels of 40 subgingival taxa mere determined in 5003 plaque samples using whole genomic DNA probes and checkerboard DNA-DNA hybridization. Clinical assessments including dichotomous measures of gingival redness, bleeding on probing, plaque accumulation and suppuration, as well as duplicate measures of pocket depth and attachment level, were made at 6 sites per tooth. The % of sites colonized by each species (prevalence) was computed for each subject. Differences in prevalence and levels among groups were sought using the Kruskal-Wallis test. Commonly detected species, such as Actinomyces naeslundii genospecies 2, Streptococcus sanguis and Streptococcus oralis did not differ significantly among subject groups. After adjusting for multiple comparisons, 4 species were significantly elevated and at greater prevalence in the periodontitis group. Mean % of sites (+/-SEM) colonized by Bacteroides forsythus was 10+/-3, 12+/-2 and 40+/-2 (p<0.001) for healthy, elder and periodontitis groups respectively. The odds ratio was 14.4:1 that a subject had periodontitis when B. forsythus was detected at greater than or equal to 5% of sampled sites. Mean prevalence for Porphyromonas gingivalis in healthy, elder and periodontitis subjects was 4+/-2, 5+/-2 and 23+/-2 respectively (p<0.001); for Treponema denticola 12+/-4, 10+/-3 and 30+/-2 (p<0.001) and for Selenomonas noxia 6+/-2, 7+/-2 and 19+/-2 (p<0.01). Similar differences among subject groups were observed when only sites with PD 0-4 mm were analyzed. The data suggest an etiologic role for B. forsythus, P. gingivalis, T. denticola and S. noxia in adult periodontitis. C1 Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. Forsyth Dent Ctr, Dept Biostat, Boston, MA 02115 USA. Forsyth Dent Ctr, Dept Bloadhes, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Dent Ctr, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-09513, DE-10977, DE-04881] NR 31 TC 203 Z9 212 U1 2 U2 8 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD MAY PY 1998 VL 25 IS 5 BP 346 EP 353 DI 10.1111/j.1600-051X.1998.tb02454.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZP565 UT WOS:000073766200002 PM 9650869 ER PT J AU Rubin, JP Posnick, JC Yaremchuk, MJ AF Rubin, JP Posnick, JC Yaremchuk, MJ TI Role of endoscopic and distraction techniques in facial and reconstructive surgery: New technology or improved results SO JOURNAL OF CRANIOFACIAL SURGERY LA English DT Article C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, ACC 453, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1049-2275 J9 J CRANIOFAC SURG JI J. Craniofac. Surg. PD MAY PY 1998 VL 9 IS 3 BP 285 EP 299 DI 10.1097/00001665-199805000-00021 PG 15 WC Surgery SC Surgery GA ZM057 UT WOS:000073500400020 PM 9693564 ER PT J AU Tran, TA Carlson, JA Basaca, PC Mihm, MC AF Tran, TA Carlson, JA Basaca, PC Mihm, MC TI Cellular blue nevus with atypia (atypical cellular blue nevus): a clinicopathologic study of nine cases SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article AB Atypical cellular blue nevus (ACBN) has clinicopathologic features intermediate between typical cellular blue nevus (CBN) and the rare malignant blue nevus (MBN)/malignant melanoma (MM) arising in a CBN. Herein we report 9 cases of ACBN. The patients were caucasian (6 females and 3 males) with a mean and median age of 47/51 years. Two patients complained of recent changes and about half of these tumors were located on the buttocks or scalp, averaging 1.5 cm in diameter. Histologically; they were characterized by architectural atypia (infiltrative margin and/or asymmetry) and/or cytologic atypia (hypercellularity, nuclear pleomorphism, hyperchromasia, mitotic figures, and/or necrosis). Assessment of the expression of 3 tissue markers demonstrated rare solitary cell staining with oncogene product bcl-2, and a proliferative index of 23+/-19 and 39+/-30 cells/10 high power field with antibodies to PCNA and Mib-1, respectively. No significant differences were detected comparing the above levels of expression to a control group of 15 CBN; however, ACBNs tended to show a higher proliferative index by PCNA and Mib-1 as well as a significantly higher mitotic rate (1/10 HPF vs. 0; p=0.001). Analysis of DNA content showed DNA aneuploidy in both groups. Follow-up data on 9 of 9 patients showed 1 patient dead without disease and 8 alive without disease (mean/median follow-up 42/32 months, range 15-96 months). No patient during this follow-up time has experienced either a local recurrence or lymph node or visceral metastasis. These findings highlight the close resemblance of ACBN to the natural history of CBN. Nevertheless, many of the distinguishing histologic features of ACBN are also those of MBN. Because of these intermediate clinicopathologic features, ACBN warrant close scrutiny and long-term follow-up. C1 Albany Med Coll, Div Dermatopathol & Dermatol, Dept Pathol, Albany, NY 12208 USA. Massachusetts Gen Hosp, Dept Pathol, Div Dermatopathol, Boston, MA 02114 USA. RP Carlson, JA (reprint author), Albany Med Coll A 81, Div Dermatopathol, Albany, NY 12208 USA. OI Carlson, John Andrew/0000-0002-6866-6314 NR 22 TC 55 Z9 55 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAY PY 1998 VL 25 IS 5 BP 252 EP 258 DI 10.1111/j.1600-0560.1998.tb01729.x PG 7 WC Dermatology; Pathology SC Dermatology; Pathology GA ZX036 UT WOS:000074473800003 PM 9696290 ER PT J AU Carr, PL Felsenstein, D Friedman, RH AF Carr, PL Felsenstein, D Friedman, RH TI Evaluation and management of vaginitis SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE vaginitis; diagnosis; therapy; yeast vaginitis; bacterial vaginosis; trichomonas vaginitis ID RECURRENT VULVOVAGINAL CANDIDIASIS; PELVIC INFLAMMATORY DISEASE; TOPICAL INTRAVAGINAL CLINDAMYCIN; BACTERIAL VAGINOSIS; TRICHOMONAS-VAGINALIS; NONSPECIFIC VAGINITIS; CHLAMYDIA-TRACHOMATIS; CANDIDAL VAGINITIS; ANAEROBIC-BACTERIA; PRETERM DELIVERY AB OBJECTIVE: To evaluate recent advances in our understanding of the clinical relevance, diagnosis, and treatment of vaginal infections, and to determine an efficient and effective method of evaluating this clinical problem in the outpatient setting, DATA SOURCES: Relevant papers on vaginitis limited to the English language obtained through a MEDLINE search for the years 1985 to 1997 were reviewed, DATA SYNTHESIS: Techniques that enable the identification of the various strains of candida have helped lead to a better understanding of the mechanisms of recurrent candida infection, From this information a rationale for the treatment of recurrent disease can be developed. Bacterial vaginosis has been associated with complications, including upper genital tract infection, preterm delivery, and wound infection. Women undergoing pelvic surgery, procedures in pregnancy, or pregnant women at risk of preterm delivery should be evaluated for bacterial vaginosis to decrease the rate of complications associated with this condition, New, more standardized criteria for the diagnosis of bacterial vaginosis may improve diagnostic consistency among clinicians and comparability of study results, Use of topical therapies in the treatment of bacterial vaginosis are effective and associated with fewer side effects than systemic medication, Trichomonas vaginalis, although decreasing in incidence, has been associated with upper genital tract infection, Therapy of T. vaginalis infection has been complicated by an increasing incidence of resistance to metronidazole. CONCLUSIONS:Vaginitis is a common medical problem in women that is associated with significant morbidity and previously unrecognized complications. Research in recent years has improved diagnostic tools as well as treatment modalities for all forms of vaginitis. C1 Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. RP Carr, PL (reprint author), Massachusetts Gen Hosp, Womens Hlth Associates, Blake 10,32 Fruit St, Boston, MA 02114 USA. NR 119 TC 24 Z9 27 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 MAY PY 1998 VL 13 IS 5 BP 335 EP 346 DI 10.1046/j.1525-1497.1998.00101.x PG 12 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA ZN668 UT WOS:000073669700009 PM 9613891 ER PT J AU Agostini, HT Shishido-Hara, Y Baumhefner, RW Singer, EJ Ryschkewitsch, CF Stoner, GL AF Agostini, HT Shishido-Hara, Y Baumhefner, RW Singer, EJ Ryschkewitsch, CF Stoner, GL TI JC virus type 2: definition of subtypes based on DNA sequence analysis of ten complete genomes SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; CEREBROSPINAL-FLUID; BRAIN; PCR; AMPLIFICATION; INDIVIDUALS; VARIANTS; STRAIN; URINE; AIDS AB Five major genotypes of JC virus (JCV) have been defined based on nucleotide differences in the VP1 gene of the DNA sequence. These types are probably a result of virus evolution in geographically isolated population groups. One of the first genotypes identified, Type 2, was found to represent strains of Asian origin. In order to further define the spectrum within Type 2 strains, the entire 5.1 kb genome of nine urinary strains of ICV was amplified by PCR with one pair of primers. These urine samples were obtained in the USA (California and New Mexico) from three European Americans, three Native Americans, two African Americans and one Hispanic American. The complete genome of an Asian ICV strain (Tokyo-1) isolated from progressive multifocal leukoencephalopathy (PML) brain in Japan was also sequenced. Here, we report the analysis of these ten DNA sequences and their deduced protein translations. Two phylogenetically distinct subtypes of Type 2 were found, 2A and 2B, which differ from each other by 0.8-1.1% of the coding region sequence. A 215 bp product amplified with primers in the VP1 gene contains enough sequence information to distinguish the major types and subtypes of JCV and is suitable for application in viral epidemiological studies. The investigation of these genomic variations is of special interest because JCV Type 2 strains are found at a significantly higher frequency in brain tissue of patients with PML than would be predicted from their excretion in a control population. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. W Los Angeles Vet Affairs Med Ctr, Neurol Serv, Los Angeles, CA 90073 USA. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-29, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 90073] NR 32 TC 43 Z9 43 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAY PY 1998 VL 79 BP 1143 EP 1151 PN 5 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA ZL473 UT WOS:000073436400020 PM 9603329 ER PT J AU Chin, KR Pess, GM Jupiter, JB AF Chin, KR Pess, GM Jupiter, JB TI Chronic lymphocytic leukemia presenting as pyogenic arthritis of the proximal interphalangeal joint SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article AB A 66-year-old woman was seen and treated for a chronic lymphocystic leukemic infiltrate of a proximal interphalangeal joint, which presented with clinical and radiologic signs consistent with a pyogenic arthritis. Copyright (C) 1998 by the American Society for Surgery of the Hand. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Hand Surg Serv, Boston, MA USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Acc 527,15 Parkman St, Boston, MA 02114 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 1998 VL 23A IS 3 BP 545 EP 550 DI 10.1016/S0363-5023(05)80477-0 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA ZN674 UT WOS:000073670300025 PM 9620200 ER PT J AU Walter, JB Garboczi, DN Fan, QR Zhou, XZ Walker, BD Eisen, HN AF Walter, JB Garboczi, DN Fan, QR Zhou, XZ Walker, BD Eisen, HN TI A mutant human beta(2)-microglobulin can be used to generate diverse multimeric class I peptide complexes as specific probes for T cell receptors SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE recombinant MHC; MHC class I multimers; T cell receptor-specific probes; flow cytometry ID CYTOTOXIC LYMPHOCYTES-T; MHC COMPLEXES; VIRAL PEPTIDE; ANTIGEN; MOLECULE; BINDING; HLA-A2; CRYSTALLIZATION; KINETICS; AFFINITY AB Antigen-specific receptors (TCR) on CD8 T lymphocytes form relatively short-lived complexes with their natural ligands: peptides in association with major histocompatibility complex (MHC) class I molecules, which consist of a polymorphic heavy chain and a conserved light chain, beta(2)-microglobulin (beta(2)-M). To produce soluble MHC-peptide complexes in a form that would bind more stably and could be used to identify, count, and isolate CD8 T cells having the appropriate TCR, we prepared multimeric MHC-peptide complexes, Our work builds on the assembly of recombinant MHC class I peptide complexes using a mutant human beta(2)-M chain (Tyr 67 > Cys) which can form stable heterodimers with diverse MHC heavy chains. With biotin added to the SH group, the assembled MHC-peptide monomers formed multimers with avidin linked to a fluorochrome. The specific reactivity of the multimeric reagents with human and mouse cytotoxic T cells (CTL) is described, The present approach permits the production of class I multimers, without the necessity of genetic engineering each heavy chain, a significant advantage in view of the enormous polymorphism of MHC heavy chains, Because human beta(2)-M forms stable heterodimers with diverse class I heavy chains from various species (human and non human primates, mouse, etc.), this procedure is a general method for producing multimers of MHC-peptide complexes as T cell receptor-specific probes. (C) 1998 Elsevier Science B.V. All rights reserved. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Walter, JB (reprint author), MIT, Ctr Canc Res, Cambridge, MA 02139 USA. FU NIAID NIH HHS [N0IAI 45218, R0IAI 28568] NR 25 TC 5 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAY 1 PY 1998 VL 214 IS 1-2 BP 41 EP 50 DI 10.1016/S0022-1759(98)00035-0 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 101GY UT WOS:000074862300005 PM 9692857 ER PT J AU Petruzzelli, L Maduzia, L Springer, TA AF Petruzzelli, L Maduzia, L Springer, TA TI Differential requirements for LFA-1 binding to ICAM-1 and LFA-1-mediated cell aggregation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; FUNCTION-ASSOCIATED MOLECULE-1; INTERCELLULAR-ADHESION MOLECULE-1; LEUKOCYTE INTEGRIN LFA-1; BETA-SUBUNIT; COUNTER-RECEPTOR; TYROSINE PHOSPHORYLATION; LYMPHOCYTE AGGREGATION; CYTOPLASMIC DOMAIN; MAC-1 CD11B/CD18 AB Cellular adhesion through the beta(2) integrin lymphocyte function-associated Ag (LFA)-1 is a complex event involving activation, ligand binding, and cell shape changes that ultimately result in enhanced adhesion. In this report we define requirements for ligand binding and post receptor signaling by comparing two mechanisms of activation of LFA-1: 1) inside-out signaling and 2) direct activation by the beta(2) Ab, CBR LFA-1/2. Our results demonstrate that activation of LFA-1 binding to ICAM-1 by CBR LFA-1/2, in contrast to inside-out signaling mechanisms, does not require protein kinase C activation or protein phosphatase 2A activity nor is it affected by agents that interfere with reorganization of the cytoskeleton. Inhibition of protein tyrosine kinase activity does not affect ICAM-1 binding by either mechanism of activation. However, activation by either mode does require the presence of the beta cytoplasmic domain; deletion of the C-terminal phenylalanine or the five amino acid stretch between 756-762 abolished activation of LFA-1. This, combined with the observation that intracellular energy pools must be preserved, implicates the beta cytoplasmic domain in a key energy-dependent conformational change in LFA-1 that is required to achieve enhanced ligand binding. Post ligand binding events induced by both PMA and Ab stimulation, as measured by homotypic aggregation, require protein tyrosine kinase, phosphatase, and RhoA activities. By examining both ligand binding and aggregation, we have been able to dissect the signaling components critical in the multistep process of LFA-1-mediated cellular adhesion. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Petruzzelli, L (reprint author), Univ Michigan, Med Ctr, Div Hematol Oncol, 1150 W Med Ctr Dr,MSRB 3,Room 5301, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [CA31798] NR 52 TC 29 Z9 29 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1998 VL 160 IS 9 BP 4208 EP 4216 PG 9 WC Immunology SC Immunology GA ZJ528 UT WOS:000073225800011 PM 9574521 ER PT J AU Ohtsuka, Y Udaka, K Yamashiro, Y Yagita, H Okumura, K AF Ohtsuka, Y Udaka, K Yamashiro, Y Yagita, H Okumura, K TI Dystrophin acts as a transplantation rejection antigen in dystrophin-deficient mice: Implication for gene therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; T-CELL TOLERANCE; ADENOVIRUS-MEDIATED TRANSFER; MUSCLE PRECURSOR CELLS; MDX MICE; MYOBLAST TRANSPLANTATION; RECOMBINANT ADENOVIRUSES; MINIDYSTROPHIN GENE; PEPTIDE VACCINATION; IMMUNE-RESPONSES AB Duchenne muscular dystrophy is a lethal and common X-linked recessive disease caused by a defect in dystrophin. Normal myoblast transplantation and dystrophin gene transfer have been expected to correct the deficiency in the muscles, but their clinical application has been hampered by the limited preservation of dystrophin-positive myofibers. In this study we investigated the mechanism for immunologic rejection of normal C57BL/10 (B10) myoblasts transplanted into dystrophin-deficient mdr mice, an animal model of Duchenne muscular dystrophy, We found that mdr mice develop CTL specific for dystrophin itself, which were CDS dominant and restricted by H-2K(b). We identified several antigenic peptides derived from dystrophin that bind to H-2K(b) and are recognized by the mdr anti-B10 CTL. Immunologic tolerance against dystrophin was successfully induced by i.v. injection of these peptides before B10 myoblast transplantation, which resulted in sustained preservation of dystrophin-expressing myofibers in mdx mice. These results demonstrate that dystrophin is antigenic in dystrophin-deficient mice and that immunologic regimen would be necessary to achieve the persistent expression of introduced dystrophin in the muscles of dystrophin-deficient individuals. C1 Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. Juntendo Univ, Sch Med, Dept Pediat, Tokyo 113, Japan. Kyoto Univ, JST, PRESTO, Kyoto 606, Japan. Kyoto Univ, Dept Biophys, Kyoto 606, Japan. RP Ohtsuka, Y (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Dev Gastroenterol Lab, 149 13th St, Charlestown, MA 02129 USA. NR 43 TC 47 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 MAY 1 PY 1998 VL 160 IS 9 BP 4635 EP 4640 PG 6 WC Immunology SC Immunology GA ZJ528 UT WOS:000073225800062 PM 9574572 ER PT J AU Seckler, JI Butte, A Harrell, L Palacios, I Jang, IK AF Seckler, JI Butte, A Harrell, L Palacios, I Jang, IK TI Acute occlusion during coronary interventions: The changing pattern in the era of stents SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE acute procedural occlusion ID ABRUPT CLOSURE; FOLLOW-UP; ANGIOPLASTY; MANAGEMENT AB Acute procedural occlusion continues to be a major cause of morbidity and mortality associated with coronary interventions. The incidence, management, and clinical outcomes of procedural occlusion of 2138 patients undergoing coronary intervention were analyzed. The acute occlusion rate increased from 5.2% in 1994 to 8.0% in 1995 (p = 0.001). The success rate for managing such acute procedural occlusion improved significantly from 93% in 1994 to 100% in 1995 (p = 0.003). The composite endpoints of coronary artery bypass surgery, non-fatal myocardial infarction or death decreased from 16.4% in 1994 to 11.4% in 1995 (p = ns). The increased acute procedural occlusion rate in 1995 likely represents a more aggressive approach on more complex lesion types as well as higher total numbers of evolving myocardial infarctions, while the improvement in successful management of acute occlusion probably represents increased utilization of stents, improved and modified procedural technique and better antiplatelet/anticoagulation therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Bulfinch 105,32 Fruit St, Boston, MA 02114 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU HEALTH MANAGEMENT PUBLICATIONSINC PI WAYNE PA 950 WEST VALLEY RD, STE 2800, WAYNE, PA 19087 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD MAY PY 1998 VL 10 IS 4 BP 208 EP 212 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN292 UT WOS:000073631300004 ER PT J AU Li, GQ Chooback, L Wolfe, JT Rook, AH Felix, CA Lessin, SR Salhany, KE AF Li, GQ Chooback, L Wolfe, JT Rook, AH Felix, CA Lessin, SR Salhany, KE TI Overexpression of p53 protein in cutaneous T cell lymphoma: Relationship to large cell transformation and disease progression SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE mycosis fungoides; p53 gene mutations; sezary syndrome ID MYCOSIS-FUNGOIDES; FOLLICULAR LYMPHOMA; GENE-MUTATIONS; DNA-DAMAGE; B-CELL; C-MYC; EXPRESSION; CANCER; POLYMORPHISM; FEATURES AB The molecular mechanisms by which advanced cases of cutaneous T cell lymphoma (CTCL) (mycosis fungoides/Sezary syndrome) undergo large cell transformation (LCT) and develop the morphologic appearance of a large cell lymphoma, are undefined. We used immunohistochemical analysis and polymerase chain reaction/single strand conformational polymorphism to examine whether p53 mutations are associated with disease progression and LCT in CTCL. p53 protein immunohistochemistry was performed on 37 paraffin embedded biopsies from 27 patients with CTCL; LCT was present in 15 biopsies. Overexpression of p53 protein was found in 11 of 37 CTCL biopsies including 10 of 15 biopsies (67%) with LCT in which p53 staining was predominantly seen in large transformed cells. In contrast, p53 immunostaining was found in only one of 22 CTCL biopsies without LCT (p < 0.0004). Serial biopsies revealed acquisition of p53 expression following I;CT in two patients in whom initial diagnostic biopsies without LCT were p53 negative by immunostaining. All p53 protein positive biopsies were from advanced lesions (cutaneous tumors or extracutaneous sites); none of 12 patch/plaque stage CTCL biopsies demonstrated p53 staining. Polymerase chain reaction/single strand conformational polymorphism and sequencing analysis of p53 exons 4-8 was performed in 11 cases where frozen tissue was available. No mutations were detected in six cases positive for p53 protein expression. These results suggest overexpression of p53 protein in LCT and disease progression of CTCL by a mechanism other than p53 gene mutation, in most cases. C1 Univ Penn, Dept Dermatol, Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Med Ctr, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Lessin, SR (reprint author), Univ Penn, Dept Dermatol, Med Ctr, 217 Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [R01 CA-58841, R29 CA-55017]; NIAMS NIH HHS [T32 AR-07565] NR 35 TC 38 Z9 40 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1998 VL 110 IS 5 BP 767 EP 770 DI 10.1046/j.1523-1747.1998.00167.x PG 4 WC Dermatology SC Dermatology GA ZJ401 UT WOS:000073211600009 PM 9579543 ER PT J AU Serova, LI Saez, E Spiegelman, BM Sabban, EL AF Serova, LI Saez, E Spiegelman, BM Sabban, EL TI c-Fos deficiency inhibits induction of mRNA for some, but not all, neurotransmitter biosynthetic enzymes by immobilization stress SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE c-Fos; immobilization stress; gene expression; tyrosine hydroxylase; dopamine beta-hydroxylase; phenylethanolamine N-methyltransferase; neuropeptide Y; gender ID DOPAMINE-BETA-HYDROXYLASE; CELL-SPECIFIC EXPRESSION; TYROSINE-HYDROXYLASE; GENE-EXPRESSION; MESSENGER-RNA; RESPONSE ELEMENT; REGULATORY ELEMENTS; NEUROPEPTIDE-Y; CYCLIC-AMP; RAT-BRAIN AB Recent studies indicated that c-Fos protein may be mediating stress-elicited transcriptional activation of genes involved in neurotransmitter biosynthesis. However, direct evidence for c-Fos mediating these changes in gene expression has been lacking. Mice with disrupted c-fos gene(+/- or -/-genotypes) were used to examine the effect of immobilization stress on a group of stress-responsive genes, in male adrenals, c-Fos was found not essential for stress-elicited activation of expression of tyrosine hydroxylase, dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase, or neuropeptide Y. In females, immobilization failed to induce adrenal DBH in the c-fos-deficient mice. In brainstem, c-Fos was indispensable for elevation of DBH mRNA in both genders. The gene, gender, and tissue specificity in the requirement for G-Fos points to diversity in adaptation mechanisms to stress. C1 New York Med Coll, Dept Biochem & Mol Biol, Valhalla, NY 10595 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Sabban, EL (reprint author), New York Med Coll, Dept Biochem & Mol Biol, Basic Sci Bldg, Valhalla, NY 10595 USA. FU NINDS NIH HHS [NS 28869, NS 32166] NR 45 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1998 VL 70 IS 5 BP 1935 EP 1940 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZJ393 UT WOS:000073210500017 PM 9572277 ER PT J AU Royall, DR Cordes, JA Polk, M AF Royall, DR Cordes, JA Polk, M TI CLOX: an executive clock drawing task SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article DE dementia; Alzheimer's; executive; assessment ID MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; DEMENTIA; ASYMMETRIES; PERFORMANCE; SCREEN AB Objective-To describe a clock drawing task (CLOX) designed to elicit executive impairment and discriminate it from non-executive constructional failure. Subjects-90 elderly subjects were studied (45 elderly and well persons from the independent living apartments of a continuing care retirement community and 45 patients with probable Alzheimer's disease). The clock drawing performance of elderly patients was compared with that of 62 young adult controls. Methods-Subjects received the CLOX, an executive test (EXIT25), and the mini mental state examination (MMSE). The CLOX is divided into an unprompted task that is sensitive to executive control (CLOX1) and a copied version that is not (CLOX2). Between rater reliability (27 subjects) was high for both subtests. Results-In elderly subjects, CLOX subscores correlated strongly with cognitive severity (CLOX1: r=-0.83 v the EXIT25; CLOX2: r=0.85 v the MMSE). EXIT25 and MMSE scores predicted CLOX1 scores independently of age or education (F(4,82)=50.7, p<0.001; R-2=0.71). The EXIT25 accounted for 68% of CLOX1 variance. Only the MMSE significantly contributed to CLOX2 scores (F(4,72)=57.2, p<0.001; R-2=0.74). CLOX subscales discriminated between patients with Alzheimer's disease and elderly controls (83.1% of cases correctly classified; Wilkes' lambda=0.48, p<0.001), and between Alzheimer's disease subgroups with and without constructional impairment (91.9% of cases correctly classified; Wilkes' lambda=0.31, p<0.001). Conclusions-The CLOX is an internally consistent measure that is easy to administer and displays good inter-rater reliability. It is strongly associated with cognitive test scores. The pattern of CLOX failures may discriminate clinical dementia subgroups. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie L Murphy Div, Geriatr Res Educ Clin Ctr, Dept Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Clin Pharmacol, San Antonio, TX 78284 USA. RP Royall, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 44 TC 390 Z9 417 U1 2 U2 16 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD MAY PY 1998 VL 64 IS 5 BP 588 EP 594 DI 10.1136/jnnp.64.5.588 PG 7 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA ZL916 UT WOS:000073486400006 PM 9598672 ER PT J AU Vonsattel, JPG DiFiglia, M AF Vonsattel, JPG DiFiglia, M TI Huntington disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article ID BASAL GANGLIA; NEURODEGENERATIVE DISEASES; TRINUCLEOTIDE REPEATS; FUNCTIONAL-ANATOMY; PROJECTION NEURONS; STRIATAL NEURONS; CAUDATE-NUCLEUS; CAG REPEATS; BRAIN; GENE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vonsattel, JPG (reprint author), MGH E, Ctr Neurosci, Lab Mol Neuropathol, CNY 6,Bldg 149, Charlestown, MA 02129 USA. FU DS NIH HHS [NINCDS 31862]; NINDS NIH HHS [NS 16367] NR 60 TC 800 Z9 817 U1 6 U2 44 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 BP 369 EP 384 PG 16 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400001 PM 9596408 ER PT J AU Cornford, EM Hyman, S Cornford, ME Damian, RT AF Cornford, EM Hyman, S Cornford, ME Damian, RT TI Glut1 glucose transporter in the primate choroid plexus endothelium SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE baboon; blood-CSF barrier; cuboidal epithelium; Glut1 glucose transporter; human; quantitative immunogold electron microscopy; vervet monkey ID BLOOD-BRAIN-BARRIER; MESSENGER-RNA; RAT; LOCALIZATION; EXPRESSION; PROTEIN; IMMUNOCYTOCHEMISTRY; CAPILLARIES; IMMUNOGOLD; MEMBRANES AB The objective of the present study was to define the cellular location of the Glut1 glucose transporter in the primate choroid plexus. Immunogold electron microscopy indicated that Glut1 epitopes were associated primarily with choroid plexus endothelial cells. Digitized analyses of electron microscopic images provided quantitative estimates of the relative number of Glut1 glucose transporter epitopes on luminal and abluminal endothelial cell membranes within the choroid plexuses. We recorded a high density of Glut1 in the microvascular endothelium of primate choroid plexus, which was consistent in vervet monkeys (5-10 Glut1 gold particles per micrometer of endothelial cell plasma membrane), as well as in baboons (5-20 Glut1 gold particles per micrometer of capillary plasma membrane). In the baboon choroid plexus, we observed that perivascular cells (presumed to be pericytes) were also Glut1-positive, but with substantially reduced activity compared with endothelial cells. Occasional Glut1-immunogold particles were also seen in the basolateral membranes of the choroid plexus cuboidal cells. Light microscopic immunocytochemistry confirmed the abundance of Glut1 immunoreactivity in choroid plexus endothelial cells of vervet monkeys and baboons. A similar pattern was observed in surgically resected human choroid plexus, suggesting differences between primates, including humans and laboratory animals. The only difference was that erythrocytes within the human choroid plexus exhibited a florid Glut1-positive response, but were weakly immunoreactive in nonhuman primates. The observation of high glucose transporter densities in choroid plexus endothelial cells is consistent with the suggestion that choroidal epithelia and capillaries provide a metabolic work capability for maintaining ionic gradients and secretory functions across the blood-CSF barriers. C1 W Los Angeles Vet Affairs Med Ctr, SW Reg VA Epilepsy Ctr W127B, Res Serv, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, SW Reg VA Epilepsy Ctr W127B, Serv Neurol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90024 USA. Harbor UCLA Med Ctr, Dept Pathol, Los Angeles, CA 90059 USA. Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA. RP Cornford, EM (reprint author), W Los Angeles Vet Affairs Med Ctr, SW Reg VA Epilepsy Ctr W127B, Res Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NINDS NIH HHS [NS 25554] NR 34 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 BP 404 EP 414 DI 10.1097/00005072-199805000-00004 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400004 PM 9596411 ER PT J AU Louis, DN Cairncross, JG AF Louis, DN Cairncross, JG TI Specific chromosomal losses predict chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. London Reg Canc Ctr, London, ON N6A 4L6, Canada. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 14 BP 472 EP 472 DI 10.1097/00005072-199805000-00027 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400026 ER PT J AU de la Monte, SM Chiche, JD Ganju, N Wands, JR Bloch, KD AF de la Monte, SM Chiche, JD Ganju, N Wands, JR Bloch, KD TI Nitric oxide synthase 3 mediates neuronal apoptosis through p53 gene modulation: Relevance to AD SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 110 BP 496 EP 496 DI 10.1097/00005072-199805000-00128 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400120 ER PT J AU Ganju, N Wands, JR de la Monte, SM AF Ganju, N Wands, JR de la Monte, SM TI Increased apoptosis with up-regulation of the p53 gene in AD brains. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 109 BP 496 EP 496 DI 10.1097/00005072-199805000-00127 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400119 ER PT J AU Stemmer-Rachamimov, AO Nielsen, GP Louis, DN AF Stemmer-Rachamimov, AO Nielsen, GP Louis, DN TI Expression of the p16 protein in the human nervous system and other tissues. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 120 BP 499 EP 499 DI 10.1097/00005072-199805000-00138 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400130 ER PT J AU Christie, RH Zipfel, WR Williams, RM Webb, WW Hyman, BT AF Christie, RH Zipfel, WR Williams, RM Webb, WW Hyman, BT TI Multiphoton imaging of Alzheimer's disease neuropathology. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cornell Univ, Ithaca, NY USA. RI Webb, Watt/B-5905-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 145 BP 505 EP 505 DI 10.1097/00005072-199805000-00163 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400155 ER PT J AU Irizarry, MC Growdon, W Gomez-Isla, T Newell, K Ingraham, A George, J Clayton, D Hyman, BT AF Irizarry, MC Growdon, W Gomez-Isla, T Newell, K Ingraham, A George, J Clayton, D Hyman, BT TI alpha-synuclein immunoreactivity in Lewy bodies and abnormal neurites in Parkinson's disease and dementia with Lewy body brain. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Illinois, Urbana, IL 61801 USA. RI Clayton, David/B-2190-2008 OI Clayton, David/0000-0002-6395-3488 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 162 BP 509 EP 509 DI 10.1097/00005072-199805000-00180 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400172 ER PT J AU Klein, AM Ferrante, RJ Kowall, NW Matthews, RT McKee, AC Kaddurak-Daouk, R Beal, MF AF Klein, AM Ferrante, RJ Kowall, NW Matthews, RT McKee, AC Kaddurak-Daouk, R Beal, MF TI Creatine and cyclocreatine attenuate MPTP neurotoxicity. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Bedford VA Med Ctr, Bedford, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 165 BP 510 EP 510 DI 10.1097/00005072-199805000-00183 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400175 ER PT J AU Berezovska, O Xia, M Knowles, R Hyman, BT AF Berezovska, O Xia, M Knowles, R Hyman, BT TI Expression of notch protein in adult brain parallels the expression of presenilin1, and is elevated in Alzheimer disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 171 BP 512 EP 512 DI 10.1097/00005072-199805000-00189 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400181 ER PT J AU Newell, KL Shen, J Berezovska, O Christie, RH Tonegawa, S Hyman, BT AF Newell, KL Shen, J Berezovska, O Christie, RH Tonegawa, S Hyman, BT TI Neuropathological studies in mice heterozygous for the disrupted presenilin-1 gene. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 Massachusetts Institute Technology, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1998 VL 57 IS 5 MA 174 BP 512 EP 512 DI 10.1097/00005072-199805000-00192 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZN115 UT WOS:000073611400184 ER PT J AU McCarthy, BJ Davis, FG Freels, S Surawicz, TS Damek, DM Grutsch, J Menck, HR Laws, ER AF McCarthy, BJ Davis, FG Freels, S Surawicz, TS Damek, DM Grutsch, J Menck, HR Laws, ER TI Factors associated with survival in patients with meningioma SO JOURNAL OF NEUROSURGERY LA English DT Article DE meningioma; benign tumor; malignant tumor; survival; age; treatment; prognosis ID INTRACRANIAL MENINGIOMA; TUMORS; BRAIN; PATTERNS; SERIES AB Object. To explore factors affecting the survival rate in patients with meningiomas, the authors used the National Cancer Data Base (NCDB), which includes tumors from approximately 1000 hospitals participating in the American College of Surgeons tumor registry program. Methods. Analysis included over 9000 cases diagnosed from 1985 to 1988 and 1990 to 1992. Survival estimates were computed and prognostic factors were identified using a proportional hazards model. The overall 5-year survival rate was 69% and it declined with patient age. This rate was 81% in patients aged 21 to 64 years and 56% for patients 65 years of age or older. When patients were grouped by the histological type of their tumors, those with benign tumors had an overall 5-year survival rate of 70%, whereas the overall 5-year survival rates in patients with atypical and malignant meningiomas were 75% and 55%, respectively. Prognostic factors for benign tumors included age at diagnosis, tumor size, whether treated surgically, hospital type, and radiation therapy; for malignant tumors, the prognostic factors included: age at diagnosis, whether treated surgically, and radiation therapy. These factors were statistically significant. The 5-year rate for recurrence of symptoms (regardless of the method of treat ment) was 19.2% for those with benign tumors and 32.4% for those with malignant tumors. In patients whose benign tumor had been completely removed, the 5-year rate of tumor recurrence was 20.5%. Conclusions. Although not population-based, the NCDB has the potential for providing pertinent information regarding patient characteristics and methods of treatment for benign, as well as malignant, brain tumors. C1 Univ Illinois, Dept Biostat & Epidemiol, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Dept Neurooncol Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Chicago Inst Neurosurg & Neurores, Div Res, Chicago, IL 60614 USA. Amer Coll Surg, Commiss Canc, Natl Canc Data Base, Chicago, IL USA. Univ Virginia, Hlth Sci Ctr, Dept Neurol Surg, Charlottesville, VA USA. RP McCarthy, BJ (reprint author), Univ Illinois, Dept Biostat & Epidemiol, 2121 W Taylor,M-C 922, Chicago, IL 60612 USA. NR 21 TC 109 Z9 111 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1998 VL 88 IS 5 BP 831 EP 839 DI 10.3171/jns.1998.88.5.0831 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZJ709 UT WOS:000073244500006 PM 9576250 ER PT J AU Moayeri, NN Henson, JW Schaefer, PW Zervas, NT AF Moayeri, NN Henson, JW Schaefer, PW Zervas, NT TI Spinal dural enhancement on magnetic resonance imaging associated with spontaneous intracranial hypotension - Report of three cases and review of the literature SO JOURNAL OF NEUROSURGERY LA English DT Review DE spontaneous intracranial hypotension; spinal dural enhancement; spinal magnetic resonance imaging; epidural blood patch; headache ID CSF PRESSURE HEADACHE; EPIDURAL BLOOD PATCH; CEREBROSPINAL-FLUID LEAK; BROWN-SEQUARD SYNDROME; MENINGEAL ENHANCEMENT; CORD HERNIATION; MRI; CISTERNOGRAPHY AB This report offers a description of typical changes seen on gadolinium-enhanced magnetic resonance (MR) imaging of the entire spine that indicate spontaneous intracranial hypotension (SIH). To the authors' knowledge, this is the first report of its kind. They describe three cases of SIH that were accompanied by dural enhancement throughout the neuraxis on imaging, with the evolution of associated subdural and epidural fluid collections in the spine. Recognition of this disorder is important to be able to distinguish it from an infectious or neoplastic process in which surgical intervention might be war ranted. Evaluation using gadolinium-enhanced cranial and spinal MR imaging in patients with postural headaches and an In-111-labeled cerebrospinal fluid leak study are discussed. Treatment with an epidural blood patch is shown to be particularly effective. with resolution of the radiological and clinical findings. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Moayeri, NN (reprint author), Brigham & Womens Hosp, Div Neurosurg, 75 Francis St, Boston, MA 02115 USA. NR 44 TC 79 Z9 83 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1998 VL 88 IS 5 BP 912 EP 918 DI 10.3171/jns.1998.88.5.0912 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZJ709 UT WOS:000073244500020 PM 9576264 ER PT J AU Russell, CD Yang, H Diethelm, AG Dubovsky, EV AF Russell, CD Yang, H Diethelm, AG Dubovsky, EV TI Prediction of renal transplant survival from early post-operative function studies with Tc99m-MAG3. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Shanxi Med Univ, 1st Hosp, Taiyuan, Peoples R China. Univ Alabama, Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 51 BP 15P EP 16P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300052 ER PT J AU Zervos, G Zusman, RR Swindle, LA Alper, NM Fischman, AJ Gewirtz, H AF Zervos, G Zusman, RR Swindle, LA Alper, NM Fischman, AJ Gewirtz, H TI Influence of nifedipine on global and regional myocardial contraction in patients with ischemic heart disease. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 175 BP 46P EP 46P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300176 ER PT J AU Brownell, AL Chen, YCI Galpern, WR Livni, E Bogdanov, M Beal, MF Isacson, O Rosen, BR Jenkins, BG AF Brownell, AL Chen, YCI Galpern, WR Livni, E Bogdanov, M Beal, MF Isacson, O Rosen, BR Jenkins, BG TI Assessment of dopaminergic neurotransmitters with WIN 35,428-compound (CFT) using PET, pharmacological MRI (phMRI), microdialysis and behavioral studies. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McLean Hosp, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 205 BP 54P EP 54P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300205 ER PT J AU Carter, EA Hartwig, W Warshaw, AL Babich, JW Fischman, AJ AF Carter, EA Hartwig, W Warshaw, AL Babich, JW Fischman, AJ TI Accumulation of a Tc-99m chemotactic peptide and FDG in an experimental model of pancreatitis. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 222 BP 58P EP 58P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300222 ER PT J AU Bonab, AA Babich, JW Madras, BK Meltzer, PC Alpert, NM Fischman, AJ AF Bonab, AA Babich, JW Madras, BK Meltzer, PC Alpert, NM Fischman, AJ TI Determination of dopamine transporter density (Bmax) and affinity (Kd) using high and low specific activity injections of C-11-Altropane. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 252 BP 66P EP 66P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300252 ER PT J AU Zervos, G Zusman, RR Swindle, LA Alpert, NM Fischman, AJ Gewirtz, H AF Zervos, G Zusman, RR Swindle, LA Alpert, NM Fischman, AJ Gewirtz, H TI Favorable effect of nifedipine on myocardial blood flow in humans with ischemic heart disease. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 344 BP 89P EP 89P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300344 ER PT J AU Callahan, RJ Desko, G Gutwillig, B Fischman, AJ Thrall, JH AF Callahan, RJ Desko, G Gutwillig, B Fischman, AJ Thrall, JH TI The planning and implementation of a hospital based service for the commercial regional distribution of F-18 FDG in a changing regulatory environment. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 567 BP 144P EP 144P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300566 ER PT J AU Khaw, BA Petrov, A Vora, K Boroujerdi, M Pak, KY Narula, J AF Khaw, BA Petrov, A Vora, K Boroujerdi, M Pak, KY Narula, J TI Tc-99m glucarate is a marker of necrosis: It does not localize in adriamycin induced apoptotic myocardial injury. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Mol Targeting Technol Inc, Malvern, PA USA. Northeastern Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 729 BP 159P EP 159P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300624 ER PT J AU Bonab, AA Alpert, NM Livni, E Christian, BT Madras, BK Fischman, AJ AF Bonab, AA Alpert, NM Livni, E Christian, BT Madras, BK Fischman, AJ TI Estimation of C-11-CFT binding potential by iterative fitting (IF) and comparison with reference region graphical (RRG) and reference fitting (RF) in monkeys. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 761 BP 167P EP 167P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300657 ER PT J AU Grachev, ID Berdichevsky, D Rauch, SL Heckers, S Alpert, NM AF Grachev, ID Berdichevsky, D Rauch, SL Heckers, S Alpert, NM TI Assessment of intersubject registration by comparison of anatomic landmarks. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 766 BP 168P EP 168P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300662 ER PT J AU Connors, JM Kronauge, JF Castronovo, F Mannting, F Jones, AG Sieff, C Antin, JH AF Connors, JM Kronauge, JF Castronovo, F Mannting, F Jones, AG Sieff, C Antin, JH TI Pharmacokinetics and biodistribution of In-111-DTPA-G-CSF in non-human primates. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Partners Canc Care, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 843 BP 187P EP 187P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300740 ER PT J AU Fischman, AJ Carter, EA Yu, YM Livni, E Babich, JW Bonab, AA Young, VR Burke, JF Alpert, NM Tompkins, RG AF Fischman, AJ Carter, EA Yu, YM Livni, E Babich, JW Bonab, AA Young, VR Burke, JF Alpert, NM Tompkins, RG TI Measurement of muscle protein synthesis by PET with L-[methyl-C-11] methionine: Validation and human experience. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 876 BP 195P EP 195P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300773 ER PT J AU Gordon, CM Dougherty, DD Rauch, SL Emans, SJ Grace, E Lamm, RL Majzoub, JA Alpert, NM Fischman, AJ AF Gordon, CM Dougherty, DD Rauch, SL Emans, SJ Grace, E Lamm, RL Majzoub, JA Alpert, NM Fischman, AJ TI Regional cerebral blood flow differences during high-caloric food challenge in patients with anorexia nervosa vs normal controls. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 909 BP 203P EP 203P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300807 ER PT J AU Kosslyn, SM Thompson, WL Gitelman, DR Alpert, NM AF Kosslyn, SM Thompson, WL Gitelman, DR Alpert, NM TI Neural systems that encode categorical versus coordinate spatial relations representations: PET investigations. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 917 BP 205P EP 205P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300815 ER PT J AU Morris, ED Chefer, SI Lane, MA Muzic, RF Wong, DF Dannals, RF Matochik, JA Bonab, AA Villemagne, VL Grant, SJ Ingram, DK Roth, GS London, ED AF Morris, ED Chefer, SI Lane, MA Muzic, RF Wong, DF Dannals, RF Matochik, JA Bonab, AA Villemagne, VL Grant, SJ Ingram, DK Roth, GS London, ED TI Effect of age on D2 dopamine receptor binding measured with 11-C-raclopride and PET in rhesus monkeys. Partial volume correction reduces the apparent rate of decline with age. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIDA, Baltimore, MD USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 924 BP 207P EP 207P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300822 ER PT J AU Mercier, G Pourdehnad, M Alavi, A Reivich, M Mozley, D Fischman, A Lanser, M AF Mercier, G Pourdehnad, M Alavi, A Reivich, M Mozley, D Fischman, A Lanser, M TI Imaging dopamine transporters with I-123 altropane: Preliminary report of a phase 1 clinical trial. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Life Sci, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 952 BP 214P EP 214P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300850 ER PT J AU Maresca, KP Rose, DJ Bonavia, GH Graham, W Fischman, AJ Babich, JW Zubieta, J AF Maresca, KP Rose, DJ Bonavia, GH Graham, W Fischman, AJ Babich, JW Zubieta, J TI Synthesis and characterization of rhenium organo-hydrazino with thiolate coligands. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Syracuse Univ, Syracuse, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 975 BP 220P EP 220P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300874 ER PT J AU Papisov, MI Babich, JW Barzana, M Hillier, S Graham-Coco, W Fischman, AJ AF Papisov, MI Babich, JW Barzana, M Hillier, S Graham-Coco, W Fischman, AJ TI Model multivalent radiopharmaceuticals targeted with chemotactic peptide (f-Met-Leu-Phe) SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 988 BP 223P EP 223P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300888 ER PT J AU Rose, DJ Graham, W Hillier, S Fischman, AJ Zubieta, J Babich, JW AF Rose, DJ Graham, W Hillier, S Fischman, AJ Zubieta, J Babich, JW TI Evaluation of neutral indium-111 and gallium-67 complexes of tris(2-mercaptoethyl)amine (NS3) in rats. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Syracuse Univ, Syracuse, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1029 BP 233P EP 233P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300929 ER PT J AU Jacobs, A Tjuvajev, JG Joshi, R Herrlinger, U Balatoni, J Finn, R Breakefield, XO Blasberg, RG AF Jacobs, A Tjuvajev, JG Joshi, R Herrlinger, U Balatoni, J Finn, R Breakefield, XO Blasberg, RG TI Monitoring HSV-1-tk and lacZ gene delivery and co-expression by a replication-conditional HSV-1 vector in 9L gliosarcoma cells: Implications for therapeutic gene imaging in vivo. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1042 BP 236P EP 236P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300942 ER PT J AU Babich, JW Bonab, AA Alpert, NM Meltzer, PC Madras, BK Fischman, AJ AF Babich, JW Bonab, AA Alpert, NM Meltzer, PC Madras, BK Fischman, AJ TI C-11 Methyl-3 beta-[4-Fluorophenyl]-N-iodo-E-allyl-1 alpha H, 5(alpha)H-nortropane-2 beta-carboxylate: A highly selective DAT ligand for PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1049 BP 238P EP 238P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300949 ER PT J AU Callahan, RJ Babich, JW Barrow, SA Dragotakes, SC Fischman, AJ AF Callahan, RJ Babich, JW Barrow, SA Dragotakes, SC Fischman, AJ TI A phase I clinical trial of the DAT ligand I-123 altropane. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1055 BP 239P EP 239P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300955 ER PT J AU Babich, JW Pugh, ER Bernier, B Freshman, J Elmaleh, DR Fischman, AJ AF Babich, JW Pugh, ER Bernier, B Freshman, J Elmaleh, DR Fischman, AJ TI Evaluation of an automated system designed for production of I-123 radiopharmaceuticals. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Sci Res Labs, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1057 BP 240P EP 240P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560300957 ER PT J AU Carter, EA Callahan, R Wilkinson, R Tompkins, RG Graham, W Barzana, M Hillier, S Babich, JW Fischman, AJ AF Carter, EA Callahan, R Wilkinson, R Tompkins, RG Graham, W Barzana, M Hillier, S Babich, JW Fischman, AJ TI Comparison of uptake of technetium-99m-labeled chemotactic peptides and FDG in acute focal infection in the rat. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1169 BP 266P EP 266P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560301066 ER PT J AU Carter, EA Tompkins, RG Graham, W Barzana, M Hillier, S Babich, JW Fischman, AJ AF Carter, EA Tompkins, RG Graham, W Barzana, M Hillier, S Babich, JW Fischman, AJ TI Accumulation of a Tc-99m chemotactic peptide and FDG by sterile inflammation in rats. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1168 BP 266P EP 266P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560301065 ER PT J AU Elmaleh, DR Babich, JW Graham, W Fischman, AJ AF Elmaleh, DR Babich, JW Graham, W Fischman, AJ TI Tc-99m-biotin analogs for infection imaging without pre- or post targeting with avidin-antibody conjugates. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1173 BP 267P EP 267P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560301070 ER PT J AU Khaw, BA Wu, L Rammohan, R Nicol, PD Narula, J AF Khaw, BA Wu, L Rammohan, R Nicol, PD Narula, J TI 10,000 times more sensitive radioimmunoassay for myosin heavy chain fragment for early detection of acute myocardial infarction. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Northeastern Univ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Allegheny Gen Hosp, Philadelphia, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1998 VL 39 IS 5 SU S MA 1177 BP 268P EP 268P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM639 UT WOS:000073560301074 ER PT J AU Glowacki, J AF Glowacki, J TI Experimental reconstruction of the mandible using polylactic acid tubes and basic fibroblast growth factor in alloplastic scaffolds SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, MGH Skeletal Biol Res Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Skeletal Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Glowacki, J (reprint author), Massachusetts Gen Hosp, MGH Skeletal Biol Res Ctr, Boston, MA 02114 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 1998 VL 56 IS 5 BP 626 EP 627 DI 10.1016/S0278-2391(98)90464-5 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZL889 UT WOS:000073483700020 ER PT J AU Kaban, LB Padwa, BL Mulliken, JB AF Kaban, LB Padwa, BL Mulliken, JB TI Surgical correction of mandibular hypoplasia in hemifacial microsomia: The case for treatment in early childhood SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Kaban, LB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Warren 1201, Boston, MA 02114 USA. NR 27 TC 29 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 1998 VL 56 IS 5 BP 628 EP 638 DI 10.1016/S0278-2391(98)90465-7 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZL889 UT WOS:000073483700021 PM 9590345 ER PT J AU Ramamurti, BS Estok, DM Jasty, M Harris, WH AF Ramamurti, BS Estok, DM Jasty, M Harris, WH TI Analysis of the kinematics of different hip simulators used to study wear of candidate materials for the articulation of total hip arthroplasties SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Orthopaedic-Research-Society CY FEB 18-22, 1996 CL ATLANTA, GEORGIA SP Orthopaed Res Soc ID POLYETHYLENE WEAR; JOINT SIMULATOR; PROSTHESES AB We developed an analytical technique to determine the paths traced by specific points on the femoral head against the acetabulum in the human hip joint during gait. The purpose of the study was to apply this technique to the mechanical hip simulators chosen to conduct wear tests on polymeric acetabular liners used in total hip replacements. These simulators differ from one another in the type of motion produced, apart from other variables such as type of lubricant and head position. Due to the variation in the kinematics between the machines, the paths traced by the points on the femoral head against the acetabular liner ranged from simple linear traces to figure-8 loops and quasi-elliptical paths during a single simulator cycle. The distances traveled by these points during the same period also varied appreciably among the different hip simulator designs. These results are important when combined with other studies that have shown that kinematics can play an important role in the outcome of in vitro wear experiments. The kinematic differences quantified in this study can partially explain the substantial differences in wear data reported from different simulator designs and also underscore the usefulness of the technique described in this study in judging the results from different hip simulator experiments. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, Grj 1126,32 Fruit St, Boston, MA 02114 USA. NR 20 TC 30 Z9 30 U1 0 U2 4 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAY PY 1998 VL 16 IS 3 BP 365 EP 369 DI 10.1002/jor.1100160313 PG 5 WC Orthopedics SC Orthopedics GA 101FB UT WOS:000074858000012 PM 9671932 ER PT J AU Hoppin, AG Kaplan, LM Zurakowski, D Leichtner, AM Bousvaros, A AF Hoppin, AG Kaplan, LM Zurakowski, D Leichtner, AM Bousvaros, A TI Serum leptin in children and young adults with inflammatory bowel disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE Crohn's disease; growth failure; leptin; malnutrition; ulcerative colitis ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; NECROSIS-FACTOR-ALPHA; CROHNS-DISEASE; ULCERATIVE-COLITIS; ENERGY-EXPENDITURE; GENE-PRODUCT; WEIGHT; ADOLESCENTS; RECEPTOR; PLASMA AB Background: Pediatric inflammatory bowel disease is often associated with growth failure and inadequate energy intake. Although several circulating cytokines are known to be elevated in inflammatory bowel disease, the mechanism for the related anorexia has not been described. Leptin is a newly recognized circulating protein that is an important regulator of appetite and energy metabolism; leptin levels are elevated in several animal models of inflammation. This study was conducted to determine whether serum leptin levels are elevated in young patients with inflammatory bowel disease, Methods: One hundred twelve children and young adults with Crohn's disease or ulcerative colitis were studied prospectively. Forty-two patients with other gastrointestinal illnesses were used as control subjects. Height, weight, erythrocyte sedimentation rate, serum albumin concentration, and clinical information were collected prospectively, and leptin was measured by radioimmunoassay of stored serum. Results: No significant differences in leptin levels were found among disease groups or control subjects. Body mass index and gender were the only independent predictors of serum leptin in all groups examined. Disease activity varied inversely with serum leptin in patients with Crohn's disease, but these differences were explained entirely by variations in body mass index. Conclusions: The determinants of serum leptin were the same in young patients with inflammatory bowel disease as in normal populations, indicating that alterations in leptin levels are unlikely to mediate the anorexia and growth failure associated with this disease. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Radiol,Div Biostat, Boston, MA 02115 USA. RP Hoppin, AG (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ-802,32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK40561, DK07191, DK43351] NR 37 TC 51 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAY PY 1998 VL 26 IS 5 BP 500 EP 505 DI 10.1097/00005176-199805000-00003 PG 6 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA ZK746 UT WOS:000073358400003 PM 9586759 ER PT J AU Goldstein, AM Davenport, T Sheridan, RL AF Goldstein, AM Davenport, T Sheridan, RL TI Junctional epidermolysis bullosa: Diagnosis and management of a patient with the Herlitz variant SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE junctional epidermolysis bullosa; Herlitz; complications; management ID GENE; IDENTIFICATION; DELETION; LETALIS AB A case of Herlitz-type epidermolysis bullosa (EB) is reported. The baby was born after a normal, full-term pregnancy with blisters on his extremities. Over the next several months, progressive skin sloughing involving 95% of his body surface area developed, including gastrointestinal, laryngeal, tracheobronchial, and corneal involvement. The diagnosis of junctional EB, Herlitz type, was made using clinical, electron microscopic, and immunohistochemical criteria. Despite meticulous wound care, aggressive nutritional support, and continuous antimicrobial therapy, the baby died at 9 months of age. This report discusses the presentation, complications, and management of this unusual and tragic disease. Copyright (C) 1998 by W.B. Saunders Company. C1 Shriners Burns Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Sheridan, RL (reprint author), Shriners Burns Inst, 51 Blossom St, Boston, MA 02114 USA. NR 14 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD MAY PY 1998 VL 33 IS 5 BP 756 EP 758 DI 10.1016/S0022-3468(98)90210-X PG 3 WC Pediatrics; Surgery SC Pediatrics; Surgery GA ZM669 UT WOS:000073564000026 PM 9607491 ER PT J AU Weirich, SD Gelberman, RH Best, SA Abrahamsson, SO Furcolo, DC Lins, RE AF Weirich, SD Gelberman, RH Best, SA Abrahamsson, SO Furcolo, DC Lins, RE TI Rehabilitation after subcutaneous transposition of the ulnar nerve: Immediate versus delayed mobilization SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID MEDIAL EPICONDYLECTOMY; COMPRESSION; ELBOW AB We studied 36 patients who had clinical signs and symptoms consistent with cubital tunnel syndrome and in whom nonoperative management failed. These patients underwent anterior subcutaneous transposition of the ulnar nerve followed by either immediate (20 patients) or delayed (16 patients) mobilization. All patients were evaluated with an outcomes assessment questionnaire, and 35 of the 36 were given repeat physical examinations. After surgery, there were no significant differences between the two groups in pain relief, weakness, or patient satisfaction (71% of the immediate mobilization group and 74% of the delayed group) were satisfied. Secondary quantitative outcomes such as grip strength, lateral pinch, or two-point discrimination were also not significantly different between the groups. Both groups had a statistically significant improvement in first dorsal interosseous and adductor pollicis muscle strength. In the immediate mobilization group, however, patients returned to work and resumed activities of daily living earlier (median month) than patients in the delayed mobilization group (median 2.75 months). Therefore, we conclude that anterior subcutaneous transposition provides a high degree of satisfaction and relief of symptoms regardless of when mobilization is initiated. However, immediately mobilizing the patient significantly influenced how early the patient returned to work and resumed activities of daily living. C1 Washington Univ, Sch Med, Dept Orthoped Surg, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Occupat Therapy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr Biostat, Boston, MA 02114 USA. RP Gelberman, RH (reprint author), Washington Univ, Sch Med, Dept Orthoped Surg, St Louis, MO 63110 USA. NR 30 TC 16 Z9 17 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAY-JUN PY 1998 VL 7 IS 3 BP 244 EP 249 DI 10.1016/S1058-2746(98)90052-0 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA ZY140 UT WOS:000074590300008 PM 9658349 ER PT J AU Aharonson, V Furst, M Levine, RA Chaigrecht, M Korczyn, AD AF Aharonson, V Furst, M Levine, RA Chaigrecht, M Korczyn, AD TI Lateralization and binaural discrimination of patients with pontine lesions SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AUDITORY-EVOKED-POTENTIALS; BRAIN-STEM LESIONS; MULTIPLE-SCLEROSIS; CLICK LATERALIZATION AB Lateralization and just-noticeable difference (jnd) measurements relative to the center were tested in a large group of patients with pontine lesions caused either by stroke or multiple sclerosis. Stimuli included binaural clicks, and low-and high-frequency narrow-band noise bursts. Two major types of abnormalities were revealed in the lateralization performances: perception of all stimuli, regardless of interaural differences (time and/or level) in the center of head (center-oriented), or lateralization of all stimuli to one side or the other of the head (side-oriented). The only significant correlation between jnd and lateralization performances was that an elevated jnd was always manifested in abnormal lateralization, while abnormality in lateralization did not necessarily indicate an abnormal jnd. Center-oriented lateralization was observed either for both interaural differences or only for one of them, and was found in both MS and stroke patients. All side-oriented stroke patients were similarly unable to center binaural stimuli for both time and level cues, whereas only one MS patient had this abnormality for interaural time differences, while his level performance was normal. More abnormalities were detected in the narrow band stimuli tests, although in some cases performance was more degraded for click stimuli. Lateralization tasks with high-frequency stimuli were more sensitive detectors of abnormality than jnd for any kind of stimulus, or lateralization tasks with low-frequency stimuli or clicks. (C) 1998 Acoustical Society of America. C1 Tel Aviv Univ, Fac Engn, Dept Elect Syst Engn, IL-69978 Tel Aviv, Israel. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02115 USA. Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Neurol, IL-69978 Tel Aviv, Israel. RP Tel Aviv Univ, Fac Engn, Dept Elect Syst Engn, IL-69978 Tel Aviv, Israel. EM mira@eng.tau.ac.il RI Korczyn, Amos/C-3461-2017; OI Korczyn, Amos/0000-0003-0125-2579; Aharonson, Vered/0000-0002-4406-6525 NR 21 TC 10 Z9 10 U1 1 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 1998 VL 103 IS 5 BP 2624 EP 2633 DI 10.1121/1.422783 PN 1 PG 10 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA ZM942 UT WOS:000073591800042 PM 9604357 ER PT J AU Bremer, J Rauch, PK AF Bremer, J Rauch, PK TI Children and computers: Risks and benefits SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Child Psychiat Consult Liaison Serv, Boston, MA 02114 USA. NR 3 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1998 VL 37 IS 5 BP 559 EP 560 DI 10.1097/00004583-199805000-00019 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZJ953 UT WOS:000073270300021 PM 9585659 ER PT J AU Tsao, HS Rogers, GS Sober, AJ AF Tsao, HS Rogers, GS Sober, AJ TI An estimate of the annual direct cost of treating cutaneous melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID STAGE-I MELANOMA; MALIGNANT-MELANOMA; HIGH-RISK; ADJUVANT THERAPY; CANCER CARE; SURVEILLANCE; MANAGEMENT; EXPERIENCE; DIAGNOSIS; MODEL AB Background: Although the survival benefits of early stage melanoma have been clearly documented, the potential economic impact of early versus late stage disease has not been assessed. Objective: Our purpose was to estimate the annual direct cost of diagnosing and treating melanoma, based on the number of projected cases of melanoma entering each stage in 1997. Methods: A model was constructed with assumptions derived from the literature and clinical experience at the Massachusetts General Hospital Melanoma Center and the Boston University Medical Center. Cost estimates were based on 1997 Boston area Medicare reimbursements. Results: The annual direct cost of treating newly diagnosed melanoma in 1997 was estimated to be $563 million. Stage I and Il disease each comprised about 5% of the total cost; stage III and stage IV disease consumed 34% and 55% of the total cost, respective ly. About 90% of the total annual direct cost of treating melanoma in 1997 was attributable to less than 20% of patients (those patients with advanced disease, that is, stage III and stage TV). Conclusion: In addition to the potential survival advantages, aggressive primary prevention through sun protection and intensive screening to enhance earlier detection should reduce the economic burden of melanoma care. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. RP Sober, AJ (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett Hall,6th Floor,Blossom St, Boston, MA 02114 USA. NR 35 TC 64 Z9 64 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 1998 VL 38 IS 5 BP 669 EP 680 DI 10.1016/S0190-9622(98)70195-1 PN 1 PG 12 WC Dermatology SC Dermatology GA ZL910 UT WOS:000073485800002 PM 9591809 ER PT J AU Drake, LA Scher, RK Smith, EB Faich, GA Smith, SL Hong, JJ Stiller, MJ AF Drake, LA Scher, RK Smith, EB Faich, GA Smith, SL Hong, JJ Stiller, MJ TI Effect of onychomycosis on quality of life SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB Background: Onychomycosis impairs normal nail functions, causes considerable pain, interferes with daily activities, and has negative psychosocial effects. Objective: Our purpose was to determine patients' perception of onychomycosis on the quality of life. Methods: A total of 258 patients with confirmed onychomycosis were surveyed by telephone at three centers. Responses to a standardized quality-of-life questionnaire were analyzed for patient demographics, physical and functional impact, psychosocial impact, and economic impact Results: Highest positive responses were nail-trimming problems (76%), embarrassment (74%), pain (48%), nail pressure (40%), and discomfort wearing shoes (38%). Ability to pick up small objects was impaired in 41% of subjects with fingernail involvement. More than 58 onychomycosis-related sick days and 468 medical visits (1.8 per subject) were reported during a B-month period. Conclusion: Onychomycosis has significant social? psychologic, health, and occupational effects. Relevance of quality-of-life issues to overall health, earning potential, and social functioning should prompt reconsideration of the value of aggressive treatment of and financial coverage for onychomycosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Univ Texas, Med Branch, Dept Dermatol, Galveston, TX 77550 USA. Pharmaceut Safety Assessments Inc, Narbeth, PA USA. RP Drake, LA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Dermatol BAR 604,40 Blossom St, Boston, MA 02114 USA. NR 8 TC 73 Z9 75 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 1998 VL 38 IS 5 BP 702 EP 704 DI 10.1016/S0190-9622(98)70199-9 PN 1 PG 3 WC Dermatology SC Dermatology GA ZL910 UT WOS:000073485800007 PM 9591814 ER PT J AU Lamb, PM Menaker, GM Moy, RL AF Lamb, PM Menaker, GM Moy, RL TI Multiple basal cell carcinomas of the limb after adjuvant treatment of melanoma with isolated limb perfusion SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MYCOSIS-FUNGOIDES; CUTANEOUS MALIGNANCIES C1 Univ Calif Los Angeles, Div Dermatol, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Moy, RL (reprint author), 100 UCLA Med Plaza,Suite 590, Los Angeles, CA 90024 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 1998 VL 38 IS 5 BP 767 EP 768 DI 10.1016/S0190-9622(98)70209-9 PN 1 PG 2 WC Dermatology SC Dermatology GA ZL910 UT WOS:000073485800019 PM 9591826 ER PT J AU Macario, E Emmons, KM Sorensen, G Hunt, MK Rudd, RE AF Macario, E Emmons, KM Sorensen, G Hunt, MK Rudd, RE TI Factors influencing nutrition education for patients with low literacy skills SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID CHOLESTEROL EDUCATION; COMPREHENSION; READABILITY; PARTICIPANTS; STRATEGIES; PHYSICIANS; SMOKING AB Although there has been increasing attention to cancer prevention among low-income and minority populations, only a few nutrition interventions have addressed the special needs of people with low literacy skills. To determine the best provider and the most effective format for a nutrition intervention targeting patients with low Literacy skills, we conducted interviews with literacy experts and health care providers and focus groups with members of adult basic education classes. Thirty-five literacy experts and health-center-based physicians, nurses, and nutritionists in Boston, Mass, were interviewed. In addition, 50 volunteer clients from 4 Boston-based adult basic education programs participated in 6 focus groups. Results suggested that health care providers consider nutrition to be a fundamental health education topic, but that its successful inculcation in patients with limited literacy skills is hindered mostly by insufficient provider time. Almost all providers agreed that patients need to be referred to nutritionists for nutrition education. Although most providers and patients acknowledged that patients perceive physicians to be the authorities on health, patients with low literacy skills turned first to family members and friends for health information. These results suggest that effective nutrition interventions must build on patients' social networks; appear in a visually based, interactive format; and be culturally appropriate. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Emmons, KM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, L-2,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5RO1CA59728-O3S1A1] NR 28 TC 33 Z9 35 U1 1 U2 9 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 MAY PY 1998 VL 98 IS 5 BP 559 EP 564 DI 10.1016/S0002-8223(98)00125-4 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZL506 UT WOS:000073440300014 PM 9597029 ER PT J AU Jan, MH Wang, SF Cheng, CK Chen, CY Sullivan, PE AF Jan, MH Wang, SF Cheng, CK Chen, CY Sullivan, PE TI Gain of muscle torque at low and high speed after isokinetic knee strengthening program in healthy young and older adults SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Article DE elderly; isokinetics; strengthening exercise; knee ID AGE-RELATED DIFFERENCES; DIFFERENT FIBER TYPES; LUMBAR MOTONEURONS; MOTOR UNIT; MEN; EXERCISE; WOMEN; HYPERTROPHY; SPECIFICITY; MORPHOLOGY AB Low-speed isokinetic exercise has been recommended to exert a maximal contraction and produce greater muscle torque than high-speed exercise in young adults. The purpose of this study was to compare the effectiveness of low- and high-speed isokinetic exercise programs for increasing muscle torque in young and elderly people. Twenty healthy elderly and 20 young subjects participated. The elderly subjects were divided into two groups. One group performed high-speed (300 degrees/s) isokinetic exercise training three times a week for the dominant-side knee extensor and low-speed (60 degrees/s) exercise for the non-dominant side for 6 weeks. The other group was trained using the reverse exercise regime. The training program for the young subjects was the same as that for the elderly groups. All subjects had their knee extensor torque evaluated with an isokinetic test before and at 2-week intervals during the training program. For young and elderly groups, both high- and low-speed isokinetic exercise training increased extensor torque in low- and high-speed tests. For the young group, low-speed exercise effectively improved muscle torque at low and high speeds. The improvement in slow muscle torque was significantly greater than that in fast muscle torque. For the elderly subjects, high-speed isokinetic exercise produced the greatest muscle torque at high speed in the first 2 weeks of training, and demonstrated a sharp increase in muscle torque in the final 2 weeks. Low-speed exercise frequently caused knee stress and the inability of some elder subjects to continue the exercises with maximal effort. Our findings indicate that high-speed exercise may be more appropriate for the elderly, and low-speed exercise may be more appropriate for younger people. C1 Natl Taiwan Univ, Coll Med, Sch Phys Therapy, Taipei, Taiwan. Natl Yang Ming Univ, Inst Biomed Engn, Taipei 112, Taiwan. Massachusetts Gen Hosp, Inst Hlth Profess, Grad Programs Phys Therapy, Boston, MA 02114 USA. RP Jan, MH (reprint author), Natl Taiwan Univ, Coll Med, Sch Phys Therapy, Taipei, Taiwan. OI WANG, SHWU-FEN/0000-0002-2114-2003 NR 40 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA ASIA LTD PI CENTRAL PA 3/F 13 DUDDELL STREET, CENTRAL, HONG KONG SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD MAY PY 1998 VL 97 IS 5 BP 339 EP 344 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZN096 UT WOS:000073609500006 PM 9610058 ER PT J AU Wang, F Seldin, DC Annis, B Trocha, A Johnson, RP AF Wang, F Seldin, DC Annis, B Trocha, A Johnson, RP TI Immune modulation of human B lymphocytes by gene transfer with recombinant Epstein-Barr virus amplicons SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE gene transfer; Epstein-Barr virus; antigen presentation; cytotoxic T cell; cytokine ID CONSERVED REGION; EBV RECOMBINANTS; CELLS; TYPE-1; INTERLEUKIN-4; DELETION; INVITRO; DNA; TRANSFORMATION; IDENTIFICATION AB We described previously a novel mode of gene transfer by infection of human B lymphocytes with recombinant Epstein-Barr virus (EBV) amplicons. This system was explored for its potential use in expressing various recombinant genes, including the cytokine IL-4, the HIV envelope glycoprotein (gp120) and a suicide and gag gene. Recombinant genes were present as multiple copy episomes and stable, high level recombinant gene expression could be detected by antigenic and functional assays. Amplicon-infected B cells secreted high levels of recombinant cytokine and efficiently presented recombinant antigens through classes I and IT MHC-restricted antigen processing pathways. Thus, recombinant EBV amplicons can be used to express components of the immune system or heterologous genes for immune recognition in human B cells. Combining gene transfer with EBV infection may provide unique advantages for in vitro and in vivo gene transfer. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Boston Univ, Med Ctr, Dept Med, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Microbiol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01172 USA. RP Wang, F (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 65319]; NIAID NIH HHS [AI 33327] NR 36 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAY PY 1998 VL 72 IS 1 BP 81 EP 93 DI 10.1016/S0166-0934(98)00023-8 PG 13 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA ZV289 UT WOS:000074289700009 PM 9672135 ER PT J AU Nguyen-Huynh, AT Schaffer, PA AF Nguyen-Huynh, AT Schaffer, PA TI Cellular transcription factors enhance herpes simplex virus type 1 oriS-dependent DNA replication SO JOURNAL OF VIROLOGY LA English DT Article ID IMMEDIATE-EARLY GENE; ORIGIN-BINDING-PROTEIN; EPSTEIN-BARR VIRUS; RNA POLYMERASE-II; VIRAL-DNA; FUNCTIONAL-ORGANIZATION; EQUINE HERPESVIRUS-1; PROMOTER ELEMENTS; ADENOVIRUS ORIGIN; PUTATIVE ORIGIN AB The herpes simplex virus type 1 (HSV-1) origin of DNA replication, oriS, contains three binding sites for the viral origin binding protein (OBP) flanked by transcriptional regulatory elements of the immediate-early genes encoding ICP4 and ICP22/47. To assess the role of flanking sequences in oriS function, plasmids containing oriS and either wild-type or mutant flanking sequences were tested in transient DNA replication assays. Although the ICP4 and ICP22/47 regulatory regions were shown to enhance oriS function, most individual elements in these regions, including the VP16-responsive TAATGARAT elements, were found to be dispensable for oriS function. In contrast, two oriS core-adjacent regulatory (Oscar) elements, OscarL and OscarR, at the base of the oriS palindrome were shown to enhance oriS function significantly and additively. Specifically, mutational disruption of either element reduced oriS-dependent DNA replication by 60 to 70%, and disruption of both elements reduced replication by 90%. The properties of protein-DNA complexes formed in gel mobility shift assays using uninfected and HSV-1-infected Vero cell nuclear extracts demonstrated that both OscarL and OscarR are binding sites for cellular proteins. Whereas OscarR does not correspond to the consensus binding site of any known transcription factor. OscarL contains a consensus binding site for the transcription factor Sp1. Gel mobility shift and supershift experiments using antibodies directed against members of the Sp1 family of transcription factors demonstrated the presence of Sp1 and Sp3, but not Sp2 or Sp4, in the protein-DNA complexes formed at OscarL. The abilities of OscarL and OscarR to bind their respective cellular proteins correlated directly with the efficiency of oriS-dependent DNA replication, Cooperative interactions between the Oscar-binding factors and proteins binding to adjacent OBP binding sites were not observed. Notably, Oscar element mutations that impaired oriS-dependent DNA replication had no detectable effect on either basal or induced levels of transcription from the ICP4 and ICP22/47 promoters, as determined by RNase protection assays. The Oscar elements thus appear to provide binding sites for cellular proteins that facilitate oriS-dependent DNA replication but have no effect on transcription of oriS-flanking genes. C1 Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Schaffer, PA (reprint author), Univ Penn, Sch Med, Dept Microbiol, 225A Johnson Pavil, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [R01 AI28537, R01 AI028537] NR 82 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1998 VL 72 IS 5 BP 3635 EP 3645 PG 11 WC Virology SC Virology GA ZH268 UT WOS:000073090100017 PM 9557644 ER PT J AU Lee, LY Schaffer, PA AF Lee, LY Schaffer, PA TI A virus with a mutation in the ICP4-binding site in the L/ST promoter of herpes simplex virus type 1, but not a virus with a mutation in open reading frame P, exhibits cell-type-specific expression of (gamma 1)34.5 transcripts and latency-associated transcripts SO JOURNAL OF VIROLOGY LA English DT Article ID ICP34.5 DELETION MUTANT; NON-NEUROVIRULENT; SPONTANEOUS REACTIVATION; MONOCLONAL-ANTIBODIES; GAMMA(1)34.5 GENE; STRAIN 17SYN+; L-COMPONENT; PROTEIN; REPLICATION; SEQUENCES AB The herpes simplex virus type 1 L/S junction-spanning transcripts (L/STs) are a family of multisized transcripts expressed at high levels in cells infected with mutant viruses that (i) do not express ICP4, (ii) specify forms of ICP4 unable to bind to the consensus ICP4 binding site, or (iii) contain mutations in the ICP4 binding site located at the transcriptional start site of the L/STs. By extension, the failure to detect the L/STs in wild-type virus-infected cells is due to the repressive effect of ICP4 bound to its cognate binding site upstream of the L/ST transcription initiation site. ORF-P, the first and largest open reading frame (ORF) encoded by the L/STs, overlaps >90% of the ORF encoding ORF-34.5, a putative neurovirulence factor, which is transcribed from the opposite DNA strand. Viruses with mutations in the overlapping region of ORF-P and ICP34.5 exhibit premature shutoff of infected-cell protein synthesis and are highly attenuated following intracranial inoculation of juvenile mice, To determine whether the premature protein shutoff and neuroattenuated phenotypes of ORF-P ORF-34.5 double mutants are a consequence of alterations in ORF-P, ORF-34.5, or both, viruses containing mutations only in ORF-P or only in the ICP4 binding site in the L/ST promoter were isolated and characterized. Mutant virus L/ST-n38 contains a single-base-pair transition mutation in ORF-P codon 38, resulting in translational termination of the ORF-P protein (OPP). This mutation does not alter the amino acid sequence of ICP34.5. Expression of a truncated form of OPP by mutant virus L/ST-n-38 did not result in premature shutoff of infected-cell protein synthesis and produced no other observable phenotype relative to wildtype virus in in vitro tests. Moreover, the 50% lethal dose (LD50) of L/ST-n38 was comparable to that of wild-type virus following intracranial inoculation of 3-week-old mice, as were the latency and reactivation phenotypes of the virus, These properties of L/ST-n38 indicate that the attenuated phenotype of ORF-P ORF 34.5 double mutants is a consequence of mutations that affect the function of ICP34.5 and not the function of OPP. Mutant virus L/ST-4BS contains four single-base-pair substitutions in the ICP4 binding site in the L/ST promoter that abrogate the binding of ICP4 to this site, leading to high-level expression of the L/STs and OPP, L/ST-4BS induced premature shutoff of viral and cellular protein synthesis and was slightly growth restricted in cells of neural lineage (SK-N-SH human neuroblastoma cells) but was wild type for these two parameters in cells of nonneural lineage (immortalized primate Vero cells). Of particular interest was the observation that L/ST-4BS exhibited cell-type-specific expression of both the gamma(1)34.5 transcripts and the latency-associated transcripts (LATs). Thus, expression of these transcripts was barely detectable in cells of neural lineage (NB41A3 mouse neuroblastoma cells) but was wild type in Vero cells. In vivo, L/ST-4BS was reactivated from mouse trigeminal ganglia with reduced efficiency and delayed kinetics relative to wild-type virus. L/ST-4BS was completely attenuated for neurovirulence (LD50 > 10(6) PFU) relative to wild-type virus (LD50 < 900 PFU), although the four single-base-pair substitutions lie outside the coding region for the neurovirulence factor, ICP34.5. Collectively, the complex in vitro and in vivo phenotypes of L/ST-4BS can be attributed to (i) disruptions of the ICP4 binding site in the L/ST promoter and subsequent overexpression of the L/STs and OPP; (ii) alterations in ORF-O, which is also mutated in L/ST-4BS; or (iii) alterations in other cryptic genes or cis-acting elements. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Schaffer, PA (reprint author), Univ Penn, Sch Med, Dept Microbiol, 225A Johnson Pavil,3610 Hamilton Walk, Philadelphia, PA 19104 USA. FU NCI NIH HHS [R37 CA20260, R01 CA020260]; NINDS NIH HHS [P01 NS35138, P01 NS035138] NR 50 TC 22 Z9 22 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1998 VL 72 IS 5 BP 4250 EP 4264 PG 15 WC Virology SC Virology GA ZH268 UT WOS:000073090100088 PM 9557715 ER PT J AU Akiyoshi, DE Denaro, M Zhu, HH Greenstein, JL Banerjee, P Fishman, JA AF Akiyoshi, DE Denaro, M Zhu, HH Greenstein, JL Banerjee, P Fishman, JA TI Identification of a full-length cDNA for an endogenous retrovirus of miniature swine SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; EUKARYOTIC RIBOSOMES; NUCLEOTIDE-SEQUENCE; PORCINE RETROVIRUS; MESSENGER-RNAS; DNA; TRANSPLANTATION; REGIONS; MAMMALS; GENE AB Endogenous retroviruses of swine are a concern in the use of pi g-derived tissues for xenotransplantation into humans. The nucleotide sequence of porcine endogenous retrovirus taken from lymphocytes of miniature swine (PERV-MSL) has been characterized. PERV-MSL is a type C retrovirus of 8,132 bp with the greatest nucleic acid sequence identity to gibbon ape leukemia virus and murine leukemia virus. Constitutive production of PERV-MSL RNA has been detected in normal leukocytes and in multiple organs of swine. The copy numbers of full-length PERV sequences per genome (approximately 8 to 15) vary among swine strains. The open reading frames for gag, pol, and env in PERV-MSL have over 99% amino acid sequence identity to those of Tsukuba-l retrovirus and are highly homologous to those of endogenous retrovirus of cell line PK15 (PK15-ERV). Most of the differences in the predicted amino acid sequences of PK15-ERV and PERV-MSL are in the SU (cell attachment) region of env. The existence of these PERV clones will enable studies of infection by endogenous retroviruses in xenotransplantation. C1 BioTransplant Inc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Transplant Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA. NR 43 TC 209 Z9 233 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1998 VL 72 IS 5 BP 4503 EP 4507 PG 5 WC Virology SC Virology GA ZH268 UT WOS:000073090100122 PM 9557749 ER PT J AU Holt, PR Moss, SF Heydari, AR Richardson, A AF Holt, PR Moss, SF Heydari, AR Richardson, A TI Diet restriction increases apoptosis in the gut of aging rats SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID IN-VIVO PATTERNS; SMALL-INTESTINE; CELL-DEATH; IMMUNOHISTOCHEMICAL ANALYSIS; FOOD RESTRICTION; BAK EXPRESSION; BCL-X; PROLIFERATION; AGE; NEOPLASIA AB Previous studies have shown that epithelial cell production rates are increased throughout the gastrointestinal tract in aging rats. We tested the hypothesis that alteration in cell death (apoptosis) might br involved. Fischer 344 rats aged 4-5 months and 24-25 months fed ad libitum (AL) or calorie restricted (CR) to 60% of the AL intake were studied. Epithelial cell apoptosis was determined by a terminal deoxyuridine nucleotidyl nick end labeling (TUNEL) technique validated in our laboratory, and the expression of four members of the Bcl-2 family was evaluated by Western blotting in the small intestine and colon. The apoptotic index was low in young and aging AL and young CR rats. However, CR in aging rats was associated with a significantly higher apoptotic index in the jejunum and colon. The expression of the Bcl-2 family of genes was unchanged. Enhanced apoptosis in CR may protect the gastrointestinal tract from accumulation of DNA-altered cells during the aging process. C1 Columbia Univ, St Lukes Roosevelt Hosp Ctr, Div Gastroenterol, Dept Med, New York, NY 10025 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Holt, PR (reprint author), Columbia Univ, St Lukes Roosevelt Hosp Ctr, Div Gastroenterol, Dept Med, Amsterdam Ave & 114th St, New York, NY 10025 USA. NR 35 TC 41 Z9 42 U1 0 U2 0 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 MAY PY 1998 VL 53 IS 3 BP B168 EP B172 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZM037 UT WOS:000073498400002 PM 9597039 ER PT J AU Haber, DA Fearon, ER AF Haber, DA Fearon, ER TI The promise of cancer genetics SO LANCET LA English DT Article ID TUMOR-SUPPRESSOR GENE; COLORECTAL-CANCER; OVARIAN-CANCER; ALLELIC LOSS; RETINOBLASTOMA; MUTATIONS; PROTEIN; BREAST; SUSCEPTIBILITY; AMPLIFICATION C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Michigan, Med Ctr, Dept Internal Med, Div Med & Mol Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Pathol, Ann Arbor, MI 48109 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 40 TC 49 Z9 52 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY PY 1998 VL 351 SU 2 BP 1 EP 8 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZP168 UT WOS:000073724100002 ER PT J AU Livingston, DM AF Livingston, DM TI Cancer - Foreword SO LANCET LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAY PY 1998 VL 351 SU 2 BP U2 EP U2 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZP168 UT WOS:000073724100001 ER PT J AU Lai, A Gliklich, RE Rubin, PAD AF Lai, A Gliklich, RE Rubin, PAD TI Repair of orbital blow-out fractures with nasoseptal cartilage SO LARYNGOSCOPE LA English DT Article ID FLOOR FRACTURES; RECONSTRUCTION; DEFECTS; ENOPHTHALMOS AB The goals of reconstruction in orbital blow-out fractures are to restore floor continuity, provide support of orbital contents, and prevent fibrosis of soft tissues. Although ease of use has popularized alloplasts, autogenous material provides greater biocompatibility and results in low rates of infection, extrusion, and migration. Nasoseptal cartilage is an easily accessible, abundant, autogenous source that provides support to the orbital floor and minimal donor site morbidity. Thirteen patients who presented with orbital blow out fractures underwent reconstruction with nasoseptal cartilage. Follow-up at 3 months to 4 years shows one patient with persistent manifest enophthalmos requiring further augmentation. There were no recipient or donor site complications, Nasoseptal cartilage is an underutilized and superior material for reconstruction of orbital blow-out fractures. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Div Orbit & Eye Plast, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Gliklich, RE (reprint author), 243 Charles St, Boston, MA 02114 USA. NR 28 TC 32 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 1998 VL 108 IS 5 BP 645 EP 650 DI 10.1097/00005537-199805000-00004 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA ZM323 UT WOS:000073527000004 PM 9591539 ER PT J AU Eavey, RD AF Eavey, RD TI Inlay tympanoplasty: Cartilage butterfly technique SO LARYNGOSCOPE LA English DT Article AB For closure of a nonmarginal tympanic membrane perforation, currently popular techniques utilize either an underlay or an onlay approach. However, both procedures require incising canal skin. A transcanal inlay procedure could provide theoretical advantages of ease, speed, and comfort. Specifically designed cartilage that could facilitate the transcanal approach similar to placement of a solid tube was employed and evaluated. A transcanal cartilage butterfly inlay technique was found to be efficient and effective to close a subgroup of small-to-medium-sized tympanic membrane perforations including cases in which the condition of the tympanic membrane was somewhat hostile, Postoperative patient comfort was an additional benefit. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Eavey, RD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 57 Z9 62 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 1998 VL 108 IS 5 BP 657 EP 661 DI 10.1097/00005537-199805000-00006 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA ZM323 UT WOS:000073527000006 PM 9591541 ER PT J AU Sattler, M Salgia, R AF Sattler, M Salgia, R TI Role of the adapter protein CRKL in signal transduction of normal hematopoietic and BCR/ABL-transformed cells SO LEUKEMIA LA English DT Review DE CRKL; CRK; BCR/ABL; signal transduction; hematopoietic growth factor; cytoskeleton ID CHRONIC MYELOGENOUS LEUKEMIA; ABL TYROSINE KINASE; SRC HOMOLOGY-3 DOMAINS; SH3 DOMAIN; C-ABL; PHOSPHATIDYLINOSITOL 3-KINASE; MOLECULAR-CLONING; BINDING-PROTEIN; V-CRK; CBL AB CRKL is a 39 kDa adapter protein, originally cloned in proximity to the BCR gene on chromosome 22, which has a key regulatory role in hematopoietic cells. CRKL has one SH2 and two SH3 domains, with 60% homology to CRK II. CRKL is a prominent substrate of the BCR/ABL oncoprotein in chronic myelogenous leukemia and binds to both BCR/ABL and c-ABL. CRKL has been shown to be tryosine phosphorylated in response to normal hematopoietic growth factor receptor signaling with ligands such as thrombopoietin, erythropoietin or steel factor. Additionally, CRKL is involved in signaling initiated by crosslinking of beta integrins, and B cell or T cell receptors. Structurally, the amino-terminal SH3 domain of CRKL has been shown to bind proteins such as C3G, SOS, P13-K, c-ABL or BCR/ABL. The SH2 domain of CRKL can bind to tyrosine phosphorylated proteins such as CBL, HEF1, CAS or paxillin. This review summarizes the current knowledge on the function of this unique adapter protein in normal hematopoietic and leukemic cell signaling. C1 Dana Farber Canc Inst, Dept Adult Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75348] NR 88 TC 90 Z9 92 U1 0 U2 8 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1998 VL 12 IS 5 BP 637 EP 644 DI 10.1038/sj.leu.2401010 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA ZM558 UT WOS:000073552200001 PM 9593259 ER PT J AU Loh, ML McLean, TW Buckley, JD Howells, W Gilliland, DG Smith, FO AF Loh, ML McLean, TW Buckley, JD Howells, W Gilliland, DG Smith, FO TI Lack of TEL/AML1 fusion in pediatric AML: further evidence for lineage specificity of TEL/AML1 SO LEUKEMIA RESEARCH LA English DT Article DE acute myeloid leukemia; chromosome 12; chromosome 21; TEL; AML1; TEL/AML1; lineage specificity ID ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE; T(12-21); TEL AB Background: the TEL/AML1 fusion associated with t(12;21)(p13;q22) is the most common gene rearrangement in childhood malignancy, occurring in approximately 25% of pediatric acute lymphoblastic leukemia. The TEL/AML1 rearrangement is cryptic at the cytogenetic level but confers a favorable prognosis. The AML1 gene was first identified by virtue of its involvement in adult and pediatric acute myeloid malignancies associated with t(8;21) and t(3;21)(q26;q22.1). We have therefore determined the frequency of the TEL/AML1 fusion in pediatric myeloid leukemias by RT-PCR analysis. Methods: total RNA was isolated from cryopreserved bone marrow samples of 38 pediatric patients with AML. RNA quality was controlled for by amplification of the TEL gene. An RT-PCR assay was then used to test for the presence of the TEL/AML1 fusion. Results: 29 patients had adequate RNA for analysis. Zero out of 29 pediatric AML patients had evidence for the :TEL/AML1 fusion by RT-PCR. Conclusions: the TEL/AML1 fusion does not occur in children with AML and suggests that the TEL/AML1 rearrangement is restricted in pediatric hematologic malignancy to B lineage ALL. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Canc Grp, Arcadia, CA 91006 USA. Harvard Univ, Inst Human Genet, Howard Hughes Med Inst, Boston, MA 02115 USA. Indiana Univ, Sch Med, James Whitcomb Riley Hosp Children, Stem Cell Transplantat Program, Indianapolis, IN 46202 USA. RP Gilliland, DG (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [410CA13539] NR 21 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 1998 VL 22 IS 5 BP 461 EP 464 DI 10.1016/S0145-2126(98)00023-X PG 4 WC Oncology; Hematology SC Oncology; Hematology GA ZU635 UT WOS:000074217800010 PM 9652733 ER PT J AU Greist, JH Marks, IM Baer, L Parkin, JR Manzo, PA Mantle, JM Wenzel, KW Spierings, CJ Kobak, KA Dottl, SL Bailey, TM Forman, L AF Greist, JH Marks, IM Baer, L Parkin, JR Manzo, PA Mantle, JM Wenzel, KW Spierings, CJ Kobak, KA Dottl, SL Bailey, TM Forman, L TI Self-treatment for obsessive compulsive disorder using a manual and a computerized telephone interview: A US-UK study SO M D COMPUTING LA English DT Article ID ANXIETY DISORDERS; DOUBLE-BLIND; FOLLOW-UP; CLOMIPRAMINE; EXPOSURE; RELIABILITY; SERTRALINE; RITUALS; THERAPY; PLACEBO AB BT STEPS is a patient-centered behavioral therapy program that uses a manual and a computer-driven interactive voice response system to assess and treat obsessive compulsive disorder. This nine-step program contains a self-assessment module and a self-treatment module that provides teaching on exposure and ritual prevention. The patient reads about the steps in a manual and then uses a touch-tone telephone to contact the program, in which a recorded voice conducts the interview. Of 40 patients in an open 12-week trial in the United States and London, 35 completed the self-assessment module, and 17 completed at least two sessions of exposure and ritual prevention. The system produced statistically significant improvements on measures of obsessive compulsive disorder. C1 Dean Fdn Hlth Res & Educ, Middleton, WI USA. Inst Psychiat, Middleton, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Pfizer Inc, New York, NY USA. RP Greist, JH (reprint author), Dean Fdn Hlth Res & Educ, 2711 Allen Blvd, Middleton, WI USA. NR 40 TC 43 Z9 43 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-6811 J9 M D COMPUT JI M D Comput. PD MAY-JUN PY 1998 VL 15 IS 3 BP 149 EP 157 PG 9 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA ZN361 UT WOS:000073638200002 PM 9617085 ER PT J AU Webster, EW AF Webster, EW TI Erratum: The linear no-threshold debate: A summary (vol 25, pg 300, 1998) SO MEDICAL PHYSICS LA English DT Correction C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Webster, EW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 1998 VL 25 IS 5 BP 794 EP 794 DI 10.1118/1.598397 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZN487 UT WOS:000073650800027 ER PT J AU Patel, BK Koenig, JI Kaplan, LM Hooi, SC AF Patel, BK Koenig, JI Kaplan, LM Hooi, SC TI Increase in plasma leptin and Lep mRNA concentrations by food intake is dependent on insulin SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID OBESE GENE-EXPRESSION; WHITE ADIPOSE-TISSUE; OB-GENE; MESSENGER-RNA; RAT; MICE; PROTEIN; PRODUCT; WEIGHT; IDENTIFICATION AB Obese (Lep) gene expression and leptin secretion are regulated by changes in food intake. However, the mechanism by which leptin concentrations are altered by fasting and feeding is unclear. Since these changes occur in parallel with changes in plasma insulin, it is possible that the changes observed are mediated by insulin. To test this hypothesis, we studied the role of insulin in the regulation of Lep gene expression in epididymal fat and leptin secretion during feeding. As shown previously, fasted animals showed significant reductions in Lep mRNA, plasma leptin, and plasma insulin concentrations. Conversely, feeding increased plasma insulin, Lep mRNA, and plasma leptin. In streptozotocin (STZ)-treated animals, plasma insulin concentrations were low. This was associated with low Lep mRNA and plasma leptin concentrations. Changes in food intake, whether fasting or feeding, did not significantly alter plasma insulin levels in STZ-treated animals. Under these circumstances, Lep mRNA and plasma leptin concentrations also remained low. Our results demonstrate that the decrease in Lep mRNA and plasma leptin during fasting and the increase with feeding are dependent on changes in the plasma insulin concentration. Copyright (C) 1998 by W.B. Saunders Company. C1 Natl Univ Singapore, Fac Med, Dept Physiol, Singapore 119260, Singapore. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Hooi, SC (reprint author), Natl Univ Singapore, Fac Med, Dept Physiol, 10 Kent Ridge Cresent, Singapore 119260, Singapore. RI Hooi, Shing/C-8588-2012 NR 30 TC 49 Z9 50 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 1998 VL 47 IS 5 BP 603 EP 607 DI 10.1016/S0026-0495(98)90247-5 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZM113 UT WOS:000073506000019 PM 9591754 ER PT J AU Lohmann, R Souba, WW Zakrzewski, K Bode, BP AF Lohmann, R Souba, WW Zakrzewski, K Bode, BP TI Stimulation of rat hepatic amino acid transport by burn injury SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID TUMOR-NECROSIS-FACTOR; PLASMA-MEMBRANE VESICLES; THERMAL-INJURY; GLUTAMINE TRANSPORT; LIVER; METABOLISM; HEPATOCYTES; INFECTION; ALANINE; MUSCLE AB Burn injury accelerates hepatic amino acid metabolism, but the role of transmembrane substrate delivery in this response has not been investigated. We therefore studied the effects of cutaneous scald injury on the Na+-dependent transport of glutamine and alanine in isolated rat liver plasma membrane vesicles. Scald injury resulted in liver damage and a 1.4- to 2.3-fold and 1.5- to 2.8-fold stimulation of hepatic transport rates for glutamine and alanine, respectively, proportional to the total burned surface area (TBSA) after 24 hours. Enhanced uptake of glutamine and alanine was attributable to increases in the maximum velocity (V-max) of system N and system A activities, respectively. Hepatic amino acid transport activity remained elevated in vesicles from burned animals after 72 hours, but the degree of stimulation (1.3- to 1.7-fold for glutamine and 1.3- to 1.6-fold for alanine) was less than that observed 24 hours after thermal injury. Liver function tests returned to control values after 72 hours as well, indicating rectification of hepatic damage. In contrast to the induction of hepatic system A and system N activity in catabolic states such as cancer and endotoxemia, further studies showed that tumor necrosis factor (TNF) failed to play a significant role in burn-stimulated amino acid transport rates. When combined with plasma liver enzyme profiles, early transient hepatic amino acid transporter stimulation may support amino acid-dependent pathways involved in the repair of burn-dependent hepatic damage. Copyright (C) 1998 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bode, BP (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Cox Bldg,Room 626,100 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [1P30DK40561] NR 44 TC 15 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 1998 VL 47 IS 5 BP 608 EP 616 DI 10.1016/S0026-0495(98)90248-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZM113 UT WOS:000073506000020 PM 9591755 ER PT J AU White, MF AF White, MF TI The IRS-signalling system: A network of docking proteins that mediate insulin action SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE IRS-1 proteins; PI-3 kinase; Ras-MAP kinase; SHP2; diabetes ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; FACTOR RECEPTOR-BETA; GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE-PHOSPHATASE; REGULATORY SUBUNIT; PHOSPHOINOSITIDE 3-KINASE; HEMATOPOIETIC-CELLS; SIGNALING PATHWAYS; P85-ALPHA GENE AB New molecules discovered during the past ten years have created a rational framework to understand signalling transduction by a broad range of growth factors and cytokines, including insulin. Insulin action is initiated through the insulin receptor, a transmembrane glycoprotein with intrinsic protein tyrosine kinase activity. The tyrosine kinase mediates the insulin response through tyrosine phosphorylation of various cellular substrates, in particular the IRS-proteins. During insulin-stimulated tyrosine phosphorylation, the IRS-proteins mediate a broad biological response by binding and activating various enzymes or adapter molecules. Although we are far from a complete understanding of the insulin signalling system and its failure, enough pieces of the puzzle are falling into place that mechanism-based solutions to insulin resistance encountered with type II diabetes may soon be attainable. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Grad Program Biomed & Biol Sci, Boston, MA 02115 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK48712, DK38712, DK43808] NR 81 TC 537 Z9 558 U1 2 U2 37 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY PY 1998 VL 182 IS 1-2 BP 3 EP 11 DI 10.1023/A:1006806722619 PG 9 WC Cell Biology SC Cell Biology GA ZK620 UT WOS:000073343400002 PM 9609109 ER PT J AU Avruch, J AF Avruch, J TI Insulin signal transduction through protein kinase cascades SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Review DE insulin action; protein serine/threonine kinase; Ras-Raf; MAP kinase; ribosomal S6 protein kinase (RSKs); phosphatidylinositol-3 kinase ID GLYCOGEN-SYNTHASE KINASE-3; P70 S6 KINASE; RABBIT SKELETAL-MUSCLE; RECEPTOR TYROSINE KINASES; SERINE-THREONINE KINASE; GTP-BINDING PROTEIN; CELL-FREE-EXTRACTS; P38 MAP KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; 3T3-L1 ADIPOCYTES AB This review summarizes the evolution of ideas concerning insulin signal transduction, the current information on protein ser/thr kinase cascades as signalling intermediates, and their status as participants in insulin regulation of energy metabolism. Best characterized is the Ras-MAPK pathway, whose input is crucial to cell fate decisions, but relatively dispensable in metabolic regulation. By contrast the effecters downstream of PI-3 kinase, although less well elucidated, include elements indispensable for the insulin regulation of glucose transport, glycogen and cAMP metabolism. Considerable information has accrued on PKB/cAkt, a protein kinase that interacts directly with Ptd Ins 3'OH phosphorylated lipids, as well as some of the elements further downstream, such as glycogen synthase kinase-3 and the p70 S6 kinase. Finally, some information implicates other erk pathways (e.g. such as the SAPK/JNK pathway) and Nck/cdc42-regulated PAKs (homologs of the yeast Ste 20) as participants in the cellular response to insulin. Thus insulin recruits a broad array of protein (ser/thr) kinases in its target cells to effectuate its characteristic anabolic and anticatabolic programs. C1 Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Avruch, J (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Diabet Res Lab, Wellman 8,50 Blossom St, Boston, MA 02114 USA. NR 203 TC 271 Z9 274 U1 2 U2 25 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 EI 1573-4919 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY PY 1998 VL 182 IS 1-2 BP 31 EP 48 DI 10.1023/A:1006823109415 PG 18 WC Cell Biology SC Cell Biology GA ZK620 UT WOS:000073343400005 PM 9609112 ER PT J AU Peraldi, P Spiegelman, B AF Peraldi, P Spiegelman, B TI TNF-alpha and insulin resistance: Summary and future prospects SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE insulin resistance; TNF-alpha; obesity; insulin signaling; adipocyte; IRS-1 ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; TYROSINE KINASE-ACTIVITY; INDUCED CELL-DEATH; ADIPOSE-TISSUE; PROTEIN-KINASE; SIGNALING COMPLEX; INDUCED APOPTOSIS; FACTOR RECEPTORS; GENE-EXPRESSION AB While the causes of obesity remain elusive, the relationship between obesity and insulin resistance is a well-established fact [1]. Insulin resistance is defined as a smaller than normal response to a certain dose of insulin, and contributes to several pathological problems of obese patients such as hyperlipidemia, arteriosclerosis and hypertension. Several pieces of evidence indicate that the cytokine tumor necrosis factor a (TNF-alpha) is an important player in the state of insulin resistance observed during obesity. In this review we will try to summarize what is known about the function of TNF-alpha in insulin resistance during obesity and how TNF-alpha interferes with insulin signaling. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Spiegelman, B (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Peraldi, Pascal/O-4592-2016 OI Peraldi, Pascal/0000-0003-0205-9252 NR 58 TC 177 Z9 184 U1 1 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY PY 1998 VL 182 IS 1-2 BP 169 EP 175 DI 10.1023/A:1006865715292 PG 7 WC Cell Biology SC Cell Biology GA ZK620 UT WOS:000073343400019 PM 9609126 ER PT J AU Schmaltz, C Hardenbergh, PH Wells, A Fisher, DE AF Schmaltz, C Hardenbergh, PH Wells, A Fisher, DE TI Regulation of proliferation-survival decisions during tumor cell hypoxia SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTRACELLULAR ACIDIFICATION; INDUCED APOPTOSIS; POLY(ADP-RIBOSE) POLYMERASE; OXYGEN DISTRIBUTION; ICE/CED-3 PROTEASE; SOLID TUMORS; HL-60 CELLS; DEATH; BCL-2; TISSUE AB Hypoxia may influence tumor biology in paradoxically opposing ways: it is lethal as a direct stress trigger, yet hypoxic zones in solid tumors harbor viable cells which are particularly resistant to treatment and contribute importantly to disease relapse. To examine mechanisms underlying growth-survival decisions during hypoxia, we have compared genetically related transformed and untransformed fibroblast cells in vitro for proliferation, survival, clonogenicity, cell cycle, and p53 expression, Hypoxia induces G(0)/G(1) arrest in primary fibroblasts but triggers apoptosis in oncogene-transformed derivatives. Unexpectedly, the mechanism of apoptosis is seen to require accumulated acidosis and is rescued by enhanced buffering. The direct effect of hypoxia under nonacidotic conditions is unique to transformed cells in that they override the hypoxic G(0)/G(1) arrest of primary cells. Moreover, when uncoupled from acidosis, hypoxia enhances tumor cell viability and clonogenicity relative to normoxia. p53 is correspondingly upregulated in response to hypoxia-induced acidosis but downregulated during hypoxia without acidosis. Hypoxia may thus produce both treatment resistance and a growth advantage. Given strong evidence that hypoxic regions in solid tumors are often nonacidotic (G. Helmlinger, F. Yuan, M. Dellian, and R. K. Jain, Nat. Med. 3:177-182, 1997), this behavior may influence relapse and implicates such cells as potentially important therapeutic targets. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fisher, DE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 69531] NR 58 TC 172 Z9 176 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1998 VL 18 IS 5 BP 2845 EP 2854 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ274 UT WOS:000073197600041 PM 9566903 ER PT J AU Valverde, AM Lorenzo, M Pons, S White, MF Benito, M AF Valverde, AM Lorenzo, M Pons, S White, MF Benito, M TI Insulin receptor substrate (IRS) proteins IRS-1 and IRS-2 differential signaling in the insulin/insulin-like growth factor-I pathways in petal brown adipocytes SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PRIMARY CULTURES; GENE-EXPRESSION; IGF-I; MICE; KINASE; RAS; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; ACTIVATION; BINDING; GRB2 AB In the present study we have investigated the contribution of the insulin receptor substrate proteins (IRS-1 and IRS-2) to the insulin/insulin like growth factor I (IGF-l)-signaling pathways in fetal rat brown adipocytes, a model that expresses both insulin and IGF-I receptors. Insulin/IGF-I rapidly stimulated IRS-1 and IRS-2 tyrosine phosphorylation, their association with p85 alpha, and IRS-1- and IRS-2-associated phosphatidylinositol (PI) 3-kinase activation to the same extent, the effect of insulin being stronger than the effect of IGF-I at the same physiological dose (10 nM). Furthermore, insulin/IGF-I stimulated IRS-1-associated Grb-2 phosphorylation. However, IRS-2-associated Grb-2 phosphorylation was barely detected. Pull-down experiments with glutathione-S-transferase-fusion proteins containing SH2-domains of p85 alpha revealed a strong association between IRS-1 and IRS-2 with p85 alpha in response to insulin/IGF-I, the insulin effect being stronger than IGF-I. However, the Grb-2-SH2 domain showed functional differences. While a strong association between IRS-1/Grb-2 was found, IRS-2/Grb-2 association was virtually absent in response to insulin/IGF-I, as also demonstrated in competition studies with a phosphopeptide containing the phosphotyrosine 895 residue within the putative Grb-2-binding domain. Finally, insulin/IGF-I stimulated tyrosine phosphorylation of the three SHC proteins (46, 52, and 66 kDa). Moreover, insulin/IGF-I markedly increased the amount of Grb-2-associated SHC proteins by the same extent. Our results suggest that both IRS-1 and IRS-2 are required for phosphatidylinositol 3-kinase activation that leads to adipogenic and thermogenic differentiation of fetal brown adipose tissue; meanwhile, IRS-1 and SHC, but not IRS-2, associate with Grb-2 leading to the ras-mitogen-activated protein kinase-signaling pathway required for fetal brown adipocyte proliferation. C1 Univ Complutense, Fac Farm, Dept Bioquim & Biol Mol 2, Inst Bioquim,CSIC,Ctr Mixto, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Benito, M (reprint author), Univ Complutense, Fac Farm, Dept Bioquim & Biol Mol 2, Inst Bioquim,CSIC,Ctr Mixto, E-28040 Madrid, Spain. RI Pons , Sebastian/K-7794-2014 OI Pons , Sebastian/0000-0003-1027-0621 NR 34 TC 45 Z9 45 U1 0 U2 3 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 MAY PY 1998 VL 12 IS 5 BP 688 EP 697 DI 10.1210/me.12.5.688 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZL146 UT WOS:000073403400008 PM 9605931 ER PT J AU Hausdorff, JM Cudkowicz, ME Firtion, R Wei, JY Goldberger, AL AF Hausdorff, JM Cudkowicz, ME Firtion, R Wei, JY Goldberger, AL TI Gait variability and basal ganglia disorders: Stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease SO MOVEMENT DISORDERS LA English DT Article DE gait analysis; time series analysis; motor control ID MOTOR FUNCTION; BALANCE; MEN; AGE; PALLIDOTOMY; PARAMETERS; LENGTH; DOPA AB The basal ganglia are thought to play an important role in regulating motor programs involved in gait and in the fluidity and sequencing of movement. We postulated that the ability to maintain a steady gait, with low stride-to-stride variability of gait cycle timing and its subphases, would be diminished with both Parkinson's disease (PD) and Huntington's disease (HD). To test this hypothesis, we obtained quantitative measures of stride-to-stride variability of gait cycle timing in subjects with PD (n = 15), HD (n = 20), and disease-free controls (n = 16). All measures of gait variability were significantly increased in PD and HD. In subjects with PD and HD, gait variability measures were two and three limes that observed in control subjects, respectively. The degree of gait variability correlated with disease severity. In contrast, gait speed was significantly lower in PD, but not in HD, and average gait cycle duration and the time spent in many subphases of the gait cycle were similar in control subjects. HD subjects, and PD subjects. These findings are consistent with a differential control of gait variability, speed, and average gait cycle timing that may have implications for understanding the role of the basal ganglia in locomotor control and for quantitatively assessing gait in clinical settings. C1 Beth Israel Deaconess Med Ctr, Gerontol Div, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hausdorff, JM (reprint author), Beth Israel Deaconess Med Ctr, Gerontol Div, 330 Brookline Ave,Room KB-26, Boston, MA 02215 USA. FU NIA NIH HHS [AG-00294, AG-08812, AG-14100] NR 46 TC 361 Z9 363 U1 2 U2 37 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 1998 VL 13 IS 3 BP 428 EP 437 DI 10.1002/mds.870130310 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA ZV257 UT WOS:000074286100009 PM 9613733 ER PT J AU Chase, M Chung, RY Chiocca, EA AF Chase, M Chung, RY Chiocca, EA TI An oncolytic viral mutant that delivers the CYP2B1 transgene and augments cyclophosphamide chemotherapy SO NATURE BIOTECHNOLOGY LA English DT Article DE gene therapy; herpes simplex virus type 1; prodrug activation ID GENE-THERAPY; BRAIN-TUMORS; DNA-SYNTHESIS; VIRUS MUTANT; P53 GENE; CANCER; GLIOMAS; CELLS; ADENOVIRUS; ACTIVATION AB Herpes simplex viruses type 1 (HSV-1) with an inactivated viral ribonucleotide reductase (Hsrr, ICP6) were designed to target tumor cells with upregulated mammalian ribonucleotide reductase (mRR), an enzyme whose expression is regulated by the p16/pRB tumor suppressor pathway. A recombinant HSV-1 was generated by knock-out of Hsrr and insertion of the rat CYP2B1 transgene responsible for the bioactivation of the prodrugs, cyclophosphamide and ifosfamide. The mutant virus replicated selectively in rat and human tumor cells that express mRR. Addition of cyclophosphamide potentiated oncolytic effects against cultured tumor cells and subcutaneous tumor xenografts established in athymic mice. C1 Harvard Univ, Sch Med, Mol Neurooncol Labs, Neurosurg Serv,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Mol Neurooncol Labs, Neurosurg Serv,Massachusetts Gen Hosp, CNY6, Charlestown, MA 02129 USA. EM Chiocca@helix.MGH.Harvard.edu NR 38 TC 139 Z9 143 U1 2 U2 9 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 1998 VL 16 IS 5 BP 444 EP 448 DI 10.1038/nbt0598-444 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA ZL948 UT WOS:000073489600028 PM 9592392 ER PT J AU Nitsch, RM Kim, C Growdon, JH AF Nitsch, RM Kim, C Growdon, JH TI Vasopressin and bradykinin regulate secretory processing of the amyloid protein precursor of Alzheimer's disease SO NEUROCHEMICAL RESEARCH LA English DT Article DE amyloid; Alzheimer's disease; vasopressin; bradykinin; neuropeptides; receptors; alpha-secretase processing ID BETA-PROTEIN; PHOSPHOLIPASE-C; KINASE-C; EXPRESSION CLONING; RECEPTOR GENE; RAT-BRAIN; ACTIVATION; INHIBITION; CELLS; NEURONS AB The amyloid protein precursor (APP) can be processed via several alternative processing pathways. alpha-secretase processing by cleavage within the amyloid beta-peptide domain of APP is highly regulated by several external and internal signals including G protein-coupled receptors, protein kinase C and phospholipase A(2). In order to demonstrate that G protein-coupled neuropeptide receptors for bradykinin and vasopressin can increase alpha-secretase processing of APP, we stimulated endogenously expressed bradykinin or vasopressin receptors in cell culture with the neuropeptides and measured the secreted ectodomain (APPs) in the conditioned media. Both bradykinin and vasopressin rapidly increased phosphatidylinositol (PI) turnover in PC-12 and in NRK-49F cells, indicating that these cell lines constitutively expressed functional PI-linked receptors for these neuropeptides. Both bradykinin and vasopressin readily stimulated APPs secretion. Increased APPs secretion was concentration-dependent and saturable, and it was blocked by receptor antagonists indicating specific receptor interaction of the peptides. The bradykinin-induced increase in APPs secretion in PC-12 cells was mediated by protein kinase C (PKC), whereas vasopressin receptors in NRK-49F cells were coupled to APP processing by PKC-independent signalling pathways. Our data show that neuropeptides can modulate APP processing in cell culture. In as much as increased alpha-secretase processing is associated with decreased formation of A beta(1-40), a major constituent of amyloid plaques, our findings suggest a possible role for modulating neuropeptide receptors as a strategy for altering amyloid metabolism in Alzheimer's disease brain. C1 Univ Hamburg, Ctr Mol Neurobiol, D-20246 Hamburg, Germany. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Nitsch, RM (reprint author), Univ Hamburg, Ctr Mol Neurobiol, Martinistr 52, D-20246 Hamburg, Germany. FU NIA NIH HHS [AG 05134] NR 34 TC 35 Z9 36 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 1998 VL 23 IS 5 BP 807 EP 814 DI 10.1023/A:1022423813362 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZG369 UT WOS:000072994700029 PM 9566621 ER PT J AU Schiff, D Batchelor, T Wen, PY AF Schiff, D Batchelor, T Wen, PY TI Neurologic emergencies in cancer patients SO NEUROLOGIC CLINICS LA English DT Review ID SPINAL-CORD COMPRESSION; BONE-MARROW TRANSPLANTATION; METASTATIC BRAIN-TUMORS; EPIDURAL METASTASES; NERVOUS-SYSTEM; CEREBROVASCULAR COMPLICATIONS; INTRACRANIAL-PRESSURE; HODGKINS-DISEASE; BREAST-CANCER; LEPTOMENINGEAL METASTASIS AB Neurologic emergencies are common among cancer patients and their incidence is increasing as patients live longer as a result of improved antineoplastic therapy. This article reviews acute neurologic complications in cancer patients. Among those complications reviewed are brain metastases, epidural spinal cord compression, leptomeningeal metastases, cerebrovascular disorders, complications of antineoplastic therapy, and paraneoplastic syndromes. C1 Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Brain Tumor Ctr, Div Neurooncol, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, 75 Francis St, Boston, MA 02115 USA. NR 156 TC 11 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 1998 VL 16 IS 2 BP 449 EP + DI 10.1016/S0733-8619(05)70072-4 PG 36 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZN686 UT WOS:000073671500011 PM 9537970 ER PT J AU Cummings, JL Cyrus, PA Bieber, F Mas, J Orazem, J Gulanski, B AF Cummings, JL Cyrus, PA Bieber, F Mas, J Orazem, J Gulanski, B CA Metrifonate Study Grp TI Metrifonate treatment of the cognitive deficits of Alzheimer's disease SO NEUROLOGY LA English DT Article ID CONTROLLED TRIAL; CHOLINESTERASE INHIBITION; RATING-SCALE; HUMAN BRAIN; DEMENTIA; ACETYLCHOLINESTERASE; DICHLORVOS; CLINICIAN; BEHAVIOR; TACRINE AB The efficacy and safety of metrifonate, an acetylcholinesterase inhibitor, was evaluated clinically in patients diagnosed with mild to moderate Alzheimer's disease (AD). This was a prospective, 30-week, multicenter, double-blind, randomized, parallel group, dose-finding study, which included a 2-week screening period, a 12-week treatment period, and follow-up visits at 8 and 16 weeks post-treatment. Patients received placebo or metrifonate once daily. Metrifonate-treated patients received a loading dose of 0.5 mg/kg (25 to 45 mg), 0.9 mg/kg (45 to 80 mg), or 2.0 mg/kg (100 to 180 mg) for 2 weeks, followed by a maintenance dose of 0.2 mg/kg (10 to 20 mg), 0.3 mg/kg (15 to 25 mg), or 0.65 mg/kg (30 to 60 mg) for 10 weeks. Four hundred eighty patients were enrolled. Percentages of patients completing double-blind treatment were 96% in the placebo group and 89 to 94% in the metrifonate group. Metrifonate significantly improved cognitive ability, as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and enhanced global function, as assessed the Clinicians's Interview-Based Impression of Change with Caregiver Input (CIBIC-Plus). At 3 months, in the intent-to-treat patients, the treatment difference for the change in ADAS-Cog score in favor of metrifonate was 2.94 points (95% CI, 1.61 to 4.27; p = 0.0001). These patients also exhibited a 0.35-point improvement on the CIBIC-Plus relative to the placebo patients (95% CI, 0.15 to 0.54; p = 0.0007). Patients receiving lower drug doses had scores intermediate to those of the placebo and the 0.65 mg/kg metrifonate groups on both performance scales. The drug was well tolerated; side effects were predominantly gastrointestinal in nature, and no hepatic toxicity was observed. Therefore, in this study, metrifonate safely improved the cognitive deficits and benefited the global function of AD patients. C1 Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Neuropsychiat & Neurobehav Sect, Los Angeles, CA 90073 USA. Bayer Corp, Div Pharmaceut, West Haven, CT USA. RP Cummings, JL (reprint author), Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Neurol, 701 Westwood Plaza, Los Angeles, CA 90095 USA. NR 39 TC 128 Z9 128 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1214 EP 1221 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800010 PM 9595966 ER PT J AU Tramo, MJ Loftus, WC Stukel, TA Green, RL Weaver, JB Gazzaniga, MS AF Tramo, MJ Loftus, WC Stukel, TA Green, RL Weaver, JB Gazzaniga, MS TI Brain size, head size, and intelligence quotient in monozygotic twins SO NEUROLOGY LA English DT Article ID HUMAN CORPUS-CALLOSUM; CEREBRAL-CORTEX; ANTERIOR COMMISSURE; CORTICAL SURFACE; REARED APART; MAMMALS; AREA; SEX; AGE; SCHIZOPHRENICS AB Many studies of monozygotic (MZ) twins have revealed evidence of genetic influences on intellectual functions and their derangement in certain neurologic and psychiatric diseases afflicting the forebrain. Relatively little is known about genetic influences on the size and shape of the human forebrain and its gross morphologic subdivisions. Using MRI and quantitative image analysis techniques, we examined neuroanatomic similarities in MZ twins and their relationship to head size and intelligence quotient (IQ). ANOVA were carried out using each measure as the dependent variable and genotype, birth order, and sex, separately, as between-subject factors. Pairwise correlations between measures were also computed. We found significant effects of genotype but not birth order for the following neuroanatomic measures: forebrain volume (raw, p less than or equal to 0.0001; normalized by body weight, p = 0.0003); cortical surface area (raw, p = 0.002; normalized, p = 0.001); and callosal area (raw, p less than or equal to 0.0001; normalized by forebrain volume, p = 0.02). We also found significant effects of genotype but not birth order for head circumference (raw, p = 0.0002; normalized, p less than or equal to 0.0001) and full-scale IQ (p = 0.001). There were no significant sex effects except for raw head circumference (p = 0.03). Significant correlations were observed among forebrain volume, cortical surface area, and callosal area and between each brain measure and head circumference. There was no significant correlation between IQ and any brain measure or head circumference. These results indicate that: 1) forebrain volume, cortical surface area, and callosal area are similar in MZ twins; and 2) these brain measures are tightly correlated with one another and with head circumference but not with IQ in young, healthy adults. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Boston, MA 02114 USA. Dartmouth Coll, Program Cognit Neurosci, Lebanon, NH 03756 USA. Dartmouth Med Sch, Dept Family & Community Med, Lebanon, NH USA. Dartmouth Med Sch, Dept Biostat, Lebanon, NH USA. Dartmouth Med Sch, Epidemiol Grp, Lebanon, NH USA. Dartmouth Med Sch, Dept Psychiat, Lebanon, NH USA. Dartmouth Med Sch, Dept Radiol, Lebanon, NH USA. Univ Calif Davis, Ctr Neurosci, Davis, CA USA. RP Tramo, MJ (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. FU NIDCD NIH HHS [DC00071]; NINDS NIH HHS [NS17778] NR 82 TC 91 Z9 91 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1246 EP 1252 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800014 PM 9595970 ER PT J AU Growdon, JH Kieburtz, K McDermott, MP Panisset, M Friedman, JH AF Growdon, JH Kieburtz, K McDermott, MP Panisset, M Friedman, JH CA Parkinson Study Grp TI Levodopa improves motor function without impairing cognition in mild non-demented Parkinson's disease patients SO NEUROLOGY LA English DT Article ID FRONTAL-LOBE DYSFUNCTION; PERFORMANCE; MEMORY; IMPAIRMENT AB Objective: The objective of the study was to determine the effects of short-term levodopa administration on motor, cognitive, and psychiatric aspects of Parkinson's disease (PD). Background: The effects of levodopa on mental processes in PD are controversial. Opinions range from the claim that levodopa improves cognition to the opposite view that levodopa causes or exacerbates dementia, delusions, and hallucinations. Of the 800 idiopathic PD patients enrolled in the original DATATOP study, 387 reached the end point of functional disabilities sufficiently severe to require levodopa treatment. There were 263 men and 124 women who were comparable with regard to age, symptom duration of PD, and measures of PD severity. We compared test scores on motor performance, cognitive function, and psychiatric status before levodopa and again within 6 months after initiation of levodopa therapy. Results: Levodopa administration improved all motor functions significantly. The improvement was significantly greater in women than in men. Levodopa administration did not worsen scores on any cognitive tests, and there were quantitatively small but significant improvements in tests of frontal lobe function. Levodopa exerted only minor effects on psychiatric measures. There were small but significant decreases in scores for depression, and increases in vivid dreams and hallucinations. Conclusions: Levodopa administration for up to 6 months in dosages sufficient to improve motor function has only small effects on cognitive function and psychiatric status in mild to moderate PD patients. We conclude that motor symptoms in early PD, which result from dopamine depletion, are dissociable from cognitive functions and psychiatric status, which may be more dependent on nondopaminergic mechanisms. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Rochester, Dept Neurol, Rochester, NY 14627 USA. Univ Rochester, Dept Biostat, Rochester, NY 14627 USA. McGill Ctr Studies Aging, Verdun, PQ, Canada. Brown Univ, Mem Hosp Rhode Isl, Dept Neurol, Pawtucket, RI 02860 USA. RP Growdon, JH (reprint author), Massachusetts Gen Hosp, WAC 830, Boston, MA 02114 USA. FU NINDS NIH HHS [NS 24778] NR 29 TC 62 Z9 62 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1327 EP 1331 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800026 PM 9595982 ER PT J AU Jenkins, BG Rosas, HD Chen, YCI Makabe, T Myers, R MacDonald, M Rosen, BR Beal, MF Koroshetz, WJ AF Jenkins, BG Rosas, HD Chen, YCI Makabe, T Myers, R MacDonald, M Rosen, BR Beal, MF Koroshetz, WJ TI H-1 NMR spectroscopy studies of Huntington's disease - Correlations with CAG repeat numbers SO NEUROLOGY LA English DT Article ID TOXIN 3-NITROPROPIONIC ACID; HUMAN VISUAL-CORTEX; LACTATE RISE; METABOLISM; LENGTH; PROGRESSION; IMPAIRMENT; STIMULATION; DISORDERS; MOVEMENTS AB Huntington's disease (HD) is the result of an expanded (CAG) repeat in a gene on chromosome 4. A consequence of the gene defect may be progressive impairment of energy metabolism. We previously showed increased occipital cortex lactate in HD using localized H-1 spectroscopy. We have now extended these studies to show an almost threefold elevation in occipital cortex lactate in 31 KD patients as compared with 17 normal control subjects (p < 10(-11)). The spectra in three presymptomatic gene-positive patients were identical to normal control subjects in cortical regions, but three in eight showed elevated lactate in the striatum. Similar to recently reported increases in task-related activation of the striatum in the dominant hemisphere, we found that striatal lactate levels in HD patients were markedly asymmetric (higher on the left side). Markers of neuronal degeneration, decreased N-acetylaspartate (NAA)/creatine and increased choline/creatine levels, were symmetric. Both decreased NAA and increased lactate in the striatum significantly correlated with duration of symptoms. When divided by his or her age, an individual's striatal NAA loss and lactate increase were found to directly correlate with the subject's CAG repeat number, with correlation coefficients of 0.8 and 0.7, respectively. Similar correlations were noted between postmortem cell loss and age versus CAG repeat length. Together, these data provide further evidence for an interaction between neuronal activation and a defect in energy metabolism in HD that may extend to presymptomatic subjects. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Dept Neurol, Neurol WRN 408,32 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA40303-09A1]; NINDS NIH HHS [R01-NS32365] NR 44 TC 163 Z9 165 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1357 EP 1365 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800031 PM 9595987 ER PT J AU Shoulson, I Penney, J Kieburtz, K Oakes, D Chase, T Choi, D Marder, K Moskowitz, C Zubin, N Ventura, P Feigin, A Hickey, C Como, P Richard, IH Goldstein, J Hersch, S Bissey-Black, C Jones, R Swenson, M Bell, J Paulsen, JS Swenson, A Tawfik-Reedy, Z Orme, C Plumb, S Rudolph, A Claude, K McMullen, N Day, D Marshall, FJ Bourgeois, K Watts, A Tariot, PN Jackson, WJ Hall, WJ Maddrey, W Biziere, K Jaffe, M AF Shoulson, I Penney, J Kieburtz, K Oakes, D Chase, T Choi, D Marder, K Moskowitz, C Zubin, N Ventura, P Feigin, A Hickey, C Como, P Richard, IH Goldstein, J Hersch, S Bissey-Black, C Jones, R Swenson, M Bell, J Paulsen, JS Swenson, A Tawfik-Reedy, Z Orme, C Plumb, S Rudolph, A Claude, K McMullen, N Day, D Marshall, FJ Bourgeois, K Watts, A Tariot, PN Jackson, WJ Hall, WJ Maddrey, W Biziere, K Jaffe, M CA Huntington Study Grp TI Safety and tolerability of the free-radical scavenger OPC-14117 in Huntington's disease SO NEUROLOGY LA English DT Article ID LIQUID-CHROMATOGRAPHY; QUINOLINIC ACID; LESIONS; INHIBITION; DISORDERS; MALONATE; CHOREA AB Oxidative damage due to free-radical generation in the setting of underlying defects of neuronal energy metabolism has been implicated as a pathogenetic mechanism for Huntington's disease (HD). The authors conducted a randomized, double-blind, placebo-controlled, multicenter trial of the tolerability of OPC-14117, a lipophilic free-radical scavenger that concentrates in the brain. Ambulatory patients with HD received OPC-14117 60 mg/d, 120 mg/d, 240 mg/d, or placebo and were assessed by the Unified Huntington's Disease Rating Scale (UHDRS) for 20 weeks, including 12 or 16 weeks of assigned treatment and 8 or 4 weeks of blinded withdrawal of the study drug. Tolerability was measured by the proportion of patients completing the initial 12-week course of treatment on their originally assigned regimen. Sixty-four patients were enrolled in the study, 56 of whom completed the 12 weeks of treatment. Treatment was discontinued in four patients (1 placebo, 1 60 mg/d, 2 240 mg/d) due to asymptomatic but persistent serum elevations of liver transaminase. Two patients (1 60 mg/d and 1 120 mg/d) withdrew because of increased involuntary movements, one patient (60 mg/d) withdrew due to persistent dry eyes, and one patient (120 mg/d) withdrew because of persistent vomiting. There were no significant differences between treatment arms in the primary measures of tolerability, the frequency and types of clinical adverse events, or the clinical/functional features of HD. OPC-14117 was safe and generally well tolerated; however, elevations of liver transaminase suggested that continued surveillance monitoring is warranted in conducting more long-term studies of this antioxidant therapy. C1 Univ Rochester, Dept Neurol, Clin Trials Coordinat Ctr, Rochester, NY 14620 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NINDS, NIH, Bethesda, MD USA. Washington Univ, St Louis, MO 63130 USA. Columbia Univ, New York, NY 10027 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Calif San Diego, Med Ctr, La Jolla, CA 92093 USA. UMDNJ, Robert Wood Johnson Med Sch, Newark, NJ 07103 USA. Univ Texas, SW Med Ctr, Austin, TX 78712 USA. Otsuka Amer Pharmaceut Inc, Rockville, MD USA. RP Marshall, FJ (reprint author), Univ Rochester, Dept Neurol, Clin Trials Coordinat Ctr, 1351 Mt Hope Ave,Suite 216, Rochester, NY 14620 USA. NR 43 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1366 EP 1373 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800032 ER PT J AU Nelles, G Contois, KA Valente, SL Higgins, JL Jacobs, DH Kaplan, JD Pessin, MS AF Nelles, G Contois, KA Valente, SL Higgins, JL Jacobs, DH Kaplan, JD Pessin, MS TI Recovery following lateral medullary infarction SO NEUROLOGY LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the American-Academy-of-Neurology CY APR 12-19, 1997 CL BOSTON, MASSACHUSETTS SP Amer Acad Neurol ID STROKE; LIFE AB Lateral medullary infarction (LMI) has a well-defined clinical syndrome and vascular pathology. The functional outcome and degree of disability of patients with LMI, however, have not been as well investigated. We followed 18 consecutive patients with LMI during inpatient stroke rehabilitation. Thirteen patients were followed after discharge from the hospital over a mean time of 1 year. The degree of disability on admission and discharge from the hospital, and at follow-up was assessed using the motor component of the Functional Independence Measurement (FIM-motor). All patients were discharged home. During inpatient rehabilitation, the functional performance of all patients improved substantially from FIM-motor 50.9 +/- 13.0 (mean +/- SD) on admission to 76.9 +/- 10.5 at discharge. Patients with lower FIM-motor scores on admission had more functional improvement from admission to discharge than those with higher FIM-motor scores on admission. Patients with disease of the posterior inferior cerebellar artery showed significantly less functional improvement than patients with disease of the vertebral artery or no identified vascular pathology in the posterior circulation. In the follow-up group, the FIM-motor scores further improved to 84.6 +/- 8.4, indicating nearly full functional independence. Eighty-five percent were totally independent with ambulation. Five of seven previously working patients returned to work. Patients with LMI have few functional deficits after completion of inpatient rehabilitation, continue to improve functionally after discharge, and often resume their previous activities. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spaulding Rehabil Hosp Stroke Serv, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Tufts Univ, Sch Med, New England Med Ctr, Dept Neurol, Boston, MA 02111 USA. RP Nelles, G (reprint author), Neurol Therapiezentrum, Laarmannstr 14, D-45359 Essen, Germany. NR 20 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1418 EP 1422 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800042 PM 9595998 ER PT J AU Tatum, WO Ross, J Cole, AJ AF Tatum, WO Ross, J Cole, AJ TI Epileptic pseudodementia SO NEUROLOGY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Epilepsy-Society CY DEC 05-11, 1996 CL SAN FRANCISCO, CALIFORNIA SP Amer Epilepsy Soc ID SEIZURES AB Dementia is a frequent cause of memory loss with aging. The incidence of complex partial seizures sharply rises after age 60. Complex partial seizures that occur with subtle clinical signs or loss of awareness, or occur during sleep may defy identification. We report five elderly patients fearing dementia in whom memory dysfunction was due to unrecognized complex partial seizures. C1 Univ S Florida, Tampa Gen Hosp, Dept Neurol, Tampa, FL 33613 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Epilepsy Serv, Boston, MA USA. RP Tatum, WO (reprint author), Univ S Florida, Tampa Gen Hosp, Dept Neurol, 13801 Bruce B Downs Blvd,Suite 401, Tampa, FL 33613 USA. NR 9 TC 37 Z9 37 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1998 VL 50 IS 5 BP 1472 EP 1475 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA ZN179 UT WOS:000073617800055 PM 9596011 ER PT J AU MacNeil, MA Masland, RH AF MacNeil, MA Masland, RH TI Extreme diversity among amacrine cells: Implications for function SO NEURON LA English DT Article ID RETINAL GANGLION-CELLS; LOCAL CIRCUIT NEURONS; MONKEY STRIATE CORTEX; LATERAL GENICULATE-NUCLEUS; RABBIT RETINA; CAT RETINA; MAMMALIAN RETINA; BIPOLAR CELLS; ACCUMULATING NEURONS; DIHYDRORHODAMINE 123 AB We report a quantitative survey of the population of amacrine cells present in the retina of the rabbit. The cells' dendritic shape and level of stratification were visualized by a photochemical method in which a fluorescent product was created within an individual cell by focal irradiation of that cell's nucleus. A systematically random sample of 261 amacrine cells was examined. Four previously known amacrine cells were revealed at their correct frequencies. Our central finding is that the heterogeneous collection of other amacrine cells is broadly distributed among at least 22 types: only one type of amacrine cell makes up more than 5% of the total amacrine cell population. With these results, the program of identification and classification of retinal neurons begun by Cajal is nearing completion. The complexity encountered has implications both for the retina and for the many regions of the central nervous system where less is known. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 70 TC 304 Z9 305 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 1998 VL 20 IS 5 BP 971 EP 982 DI 10.1016/S0896-6273(00)80478-X PG 12 WC Neurosciences SC Neurosciences & Neurology GA ZQ464 UT WOS:000073864700016 PM 9620701 ER PT J AU Ogilvy, CS Carter, BS AF Ogilvy, CS Carter, BS TI A proposed comprehensive grading system to predict outcome for surgical management of intracranial aneurysms SO NEUROSURGERY LA English DT Article DE grading system; intracranial aneurysm; prognosis; surgical clipping ID SUBARACHNOID HEMORRHAGE; CEREBRAL VASOSPASM; PROGNOSTIC FACTORS; SURGERY; BLOOD; CT; AGE AB OBJECTIVE: By conducting a review of clinical outcomes for patients with aneurysms treated using current microneurosurgical techniques and intensive care unit management, we determined that grading systems based only on the clinical condition of the patient failed to produce a significant stratification of outcome between individual grades of patients. We hypothesized that outcome prediction for patients surgically treated for intracranial aneurysms could be improved by including factors other than clinical condition that were also strongly associated with outcome. METHODS: To identify potential factors for inclusion in a risk prediction tool, we conducted a multivariate logistic regression analysis of patient- and lesion-specific factors suspected to be associated with outcome in a series of 434 aneurysm operations. Factors that were strongly associated with outcome were used to develop a comprehensive grading system. In the system, 1 point is assigned for taunt and Hess Grade IV or V, Fisher Scale score of 3 or 4, aneurysm size greater than 10 mm, patient age older than 50 years, and if the lesion is a giant (greater than or equal to 25 mm) posterior circulation lesion. By adding the total points, a 5-point grading system (Grades 0-5) is obtained. RESULTS: Age of patient, size of aneurysm, severity of subarachnoid hemorrhage (Fisher Scale evaluation of density of blood present as revealed by computed tomography), and clinical condition (Hunt and Hess grade) were each independently and strongly (relative risk, >4) associated with long-term outcome. In addition, there was a trend for increased risk with larger (>25 mm) posterior circulation lesions. When applied to the study population, individual grades on the new grading scale correlated well with actual outcome. In a prospective assessment of the system as applied to an additional 72 operations with at least 1 year of follow-up, the correlation of individual grades and outcome was strong and validated the retrospective findings. CONCLUSION: This new grading system is easy to apply, separates patients into groups with markedly different outcomes, and is comprehensive, allowing for more accurate prediction of surgical outcome for both unruptured and ruptured cerebral aneurysms. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. FU PHS HHS [K08] NR 32 TC 81 Z9 85 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 1998 VL 42 IS 5 BP 959 EP 968 DI 10.1097/00006123-199805000-00001 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZK454 UT WOS:000073322500001 PM 9588539 ER PT J AU Le, SY Zhu, JJG Anthony, DC Greider, CW Black, PM AF Le, SY Zhu, JJG Anthony, DC Greider, CW Black, PM TI Telomerase activity in human gliomas SO NEUROSURGERY LA English DT Article DE cancer; glioma; malignant progression; telomerase; telomere ID HUMAN BRAIN-TUMORS; GLIOBLASTOMA-MULTIFORME; HUMAN FIBROBLASTS; CELLS; TUMORIGENESIS; LENGTH; CANCER; ACTIVATION; GENES; RNA AB OBJECTIVE: Telomerase activity, which is undetectable in most mature normal tissues, has been identified in many types of human cancers, including neuroblastomas and oligodendrogliomas. These findings suggest that a novel mechanism in addition to activation of oncogenes and inactivation of tumor suppressor genes may play an important role in tumorigenesis. The goal of the present study was to assess and correlate the telomerase activity in astrocytic gliomas of different grades. METHODS: Telomere repeat amplification protocol and Southern blot hybridization with telomere-specific probes were used to detect telomerase activity and to measure terminal restriction fragment length, respectively. RESULTS: Telomerase activity was detected in 3 of 9 (33%) low-grade astrocytomas (World Health Organization Grade II), 5 of 11 (45%) anaplastic astrocytomas (World Health Organization Grade III), 36 of 41 (89%) glioblastomas multiforme (World Health Organization Grade IV), 3 of 4 (75%) oligodendrogliomas, and none of 4 normal brain specimens. CONCLUSION: We demonstrated that telomerase activity is absent in normal brain tissues while present in most glioma samples (72%). The frequency of such activity increases with malignancy. These results suggest that telomerase activity may be used as a tumor marker and that the activation of telomerase may correlate with initiation and malignant progression of astrocytic tumors. C1 Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Neurosurg Labs, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Brain Tumor Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Pathol Dept,Neuropathol Div, Boston, MA 02115 USA. RP Black, PM (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dana Farber Canc Inst,Neurosurg Labs, Bader 3,300 Longwood Ave, Boston, MA 02115 USA. OI Anthony, Douglas/0000-0002-3815-2240 FU NIA NIH HHS [AG09383] NR 30 TC 56 Z9 62 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 1998 VL 42 IS 5 BP 1120 EP 1124 DI 10.1097/00006123-199805000-00099 PG 5 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZK454 UT WOS:000073322500088 PM 9588558 ER PT J AU Wilkins, AS Genova, LM Posten, W Kosofsky, BE AF Wilkins, AS Genova, LM Posten, W Kosofsky, BE TI Transplacental cocaine exposure 1: A rodent model SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE brain development; prenatal cocaine; prenatal malnutrition; attentional mechanisms; mouse model; behavioral teratology ID LONG-EVANS RAT; PRENATAL COCAINE; SELECTIVE ATTENTION; GESTATIONAL COCAINE; ADULT-RATS; FOLLOW-UP; BRAIN; BEHAVIOR; PREGNANCY; BLOCKING AB To characterize the transplacental effects of cocaine on the developing brain, we have developed a mouse model of gestational cocaine exposure. Pharmacokinetic analysis revealed that cocaine and its metabolites (BE, BNE, and NC) were found in fetal brain and plasma at 30 and 120 min following SC administration to embryonic day (E) 17 pregnant Swiss Webster mice. Pregnant dams injected twice daily with cocaine HCl at 20 mg/kg SC from gestational day ES to E17 (()C) demonstrated less food intake and lower percentage weight gain than vehicle-injected dams allowed access to food ad lib (SAL). A nutritionally paired control group of dams injected with saline vehicle and pair-fed with the COC dams (SPF) demonstrated the lowest percentage weight gain of all three groups. The surrogate fostered offspring of COC and SPF darns demonstrated persistent growth retardation [on postnatal days (P) 1, P9, and P50] and transient brain growth retardation ton P1 and P9) when compared to pups born to SAL dams. We conducted behavioral tests that allowed us to dissociate the indirect effect of cocaine-induced malnutrition from a direct effect of prenatal cocaine administration in altering postnatal behavior. Pups from all three groups were tested for first-order Pavlovian conditioning on P9 or P12, or for the ability to ignore redundant information in a blocking paradigm on P50 or P100. Unlike the SPF and SAL controls, COC mice (i.e., mice born to COC dams) were unable to acquire an aversion to an odor previously paired with shock on P9. This learning deficit was transient because on P12, COC mice trained on the same conditioning task displayed an aversion to the odor that was indistinguishable from the SPF and SAL controls. P50 and P100 COC mice land to a lesser extent, SPF mice) demonstrated a persistent behavioral deficit in the blocking paradigm, which may reflect alterations in selective attention. We discuss how these findings in our rodent model have developmental implications for human infants exposed to cocaine in utero. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kosofsky, BE (reprint author), Massachusetts Gen Hosp E, Lab Mol & Dev Neurosci, Bldg 149,CNY-2W,13th St, Charlestown, MA 02129 USA. EM kosofsky@helix.mgh.harvard.edu FU NIDA NIH HHS [DA08648, DA00175] NR 80 TC 32 Z9 36 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 1998 VL 20 IS 3 BP 215 EP 226 DI 10.1016/S0892-0362(97)00125-6 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA ZU241 UT WOS:000074176500001 PM 9638679 ER PT J AU Wilkins, AS Jones, K Kosofsky, BE AF Wilkins, AS Jones, K Kosofsky, BE TI Transplacental cocaine exposure 2: Effects of cocaine dose and gestational timing SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE brain development; prenatal cocaine; prenatal malnutrition; path analysis; mouse model; behavioral teratology ID SUBSEQUENT BEHAVIORAL-DEVELOPMENT; LONG-EVANS RAT; PRENATAL COCAINE; SELECTIVE ATTENTION; VISUAL-DISCRIMINATION; NORADRENERGIC BUNDLE; EARLY MALNUTRITION; DOPAMINE NEURONS; ADULT-RABBITS; D-AMPHETAMINE AB We have utilized a mouse model of transplacental cocaine exposure to investigate the effects of cocaine dose and gestational timing in altering brain and body growth and postnatal behavior in exposed offspring. Pregnant dams were injected with cocaine HCl at 40 mg/kg/day (COC 40) or 20 mg/kg/day (COC 20), or 10 mg/kg/day (COC 10) SC from embryonic day (E) 8 to E17, or cocaine HCl at 40 mg/kg/day SC from E8 to E13 (COC Early) or from E13 to E17 (COC Late) divided in two daily doses. COC 40 and COC Late dams, as well as dams in nutritionally paired control groups (injected with saline vehicle and pair-fed with the COC dams: SPF 40, SPF 20, SPF 10), demonstrated less weight gain than SAL controls (injected with saline vehicle and allowed access to food ad lib). The surrogate fostered offspring of COC 40 and SPF 40 dams demonstrated brain and body growth retardation [on postnatal day (P) 1 and P9] when compared to pups born to SAL dams. Offspring of COC Late, SPF 20, and SPF 10 dams demonstrated brain and body growth retardation on P1 when compared to pups born to SAL dams. Pups from all groups were tested for first-order Pavlovian conditioning on P9, or for the ability to ignore redundant information in a blocking paradigm on P50. Only COC 40 mice (i.e., offspring born to COC 40 dam) were unable to acquire an aversion to an odor previously paired with shock on P9. When compared with SAL controls, COC 40 mice land to a less significant extent SPF 40 mice) demonstrated a persistent behavioral deficit in the blocking paradigm on P50, which may reflect alterations in selective attention. Correlation analyses indicated that the dose and gestational timing of transplacental cocaine exposure, and varying degrees of malnutrition, had effects on blocking performance, with greater prenatal cocaine exposure and increased prenatal malnutrition resulting in more significant behavioral impairments. A path regression analysis demonstrated independent and significant effects of prenatal cocaine as well as prenatal malnutrition in contributing to impaired performance in the blocking paradigm. As suggested by the clinical literature, our preclinical data support a model whereby the dose and duration of prenatal cocaine exposure have direct effects on offspring brain and body growth and on behavioral performance. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. Brandeis Univ, Florence Heller Grad Sch, Waltham, MA 02254 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kosofsky, BE (reprint author), Massachusetts Gen Hosp E, Lab Mol & Dev Neurosci, Bldg 149,CNY-2W,13th St, Charlestown, MA 02129 USA. EM kosofsky@helix.mgh.harvard.edu FU NIDA NIH HHS [DA08648, DA00175] NR 77 TC 20 Z9 20 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 1998 VL 20 IS 3 BP 227 EP 238 DI 10.1016/S0892-0362(97)00127-X PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA ZU241 UT WOS:000074176500002 PM 9638680 ER PT J AU Wilkins, AS Marota, JJA Tabit, E Kosofsky, BE AF Wilkins, AS Marota, JJA Tabit, E Kosofsky, BE TI Transplacental cocaine exposure 3: Mechanisms underlying altered brain development SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE brain development; prenatal cocaine; prenatal malnutrition; monoamines; mouse model; behavioral teratology ID GENE-RELATED PEPTIDE; HUMAN UTERINE ARTERY; CARDIOVASCULAR-RESPONSES; CEREBRAL-CORTEX; BLOOD-PRESSURE; FETAL; TOXICITY; RATS; CONSEQUENCES; BEHAVIOR AB In a mouse model of transplacental cocaine exposure we have demonstrated alterations in brain structure and function of offspring including disturbances of brain growth, disruption of neocortical cytoarchitecture, and transient as well as persistent behavioral deficits. One mechanism by which cocaine may alter fetal brain development is through cocaine-induced alpha-adrenergic-mediated (uterine) arterial vasoconstriction. In this study pregnant Swiss Webster (SW) mice were injected with cocaine HCl (20 or 40 mg/kg, SC) without any changes evident in mean arterial blood pressure (MAP) measurements. These physiology results suggest that in our mouse model, cocaine's transplacental effects on the fetus are not due to cocaine-induced maternal vasoconstriction, nor concomitant hypoperfusion of the fetus. In a separate series of experiments, pregnant SW dams were administered cocaine HCl at 40 mg/kg/day (COC 40), 20 mg/kg/day (COC 20), or 10 mg/kg/day (COC 10) [SC, divided in two daily doses, from embryonic day (E) 8 to E17 inclusive]. Additional groups of cocaine-treated dams were administered phentolamine (5 mg/kg, SC), a short-acting alpha-adrenergic antagonist, 15 min prior to each cocaine dose (Phent COC 40, Phent COC 20, Phent COC 10). Animals born to Phent COC 40 dams demonstrated transient postnatal brain growth retardation and behavioral deficits in first-order conditioning of P9 mice comparable to mice born to COC 40 dams, which received the same regimen of cocaine injections without phentolamine pretreatment. Like COC 40 offspring, Phent COC 40 offspring also demonstrated a persistent deficit in the blocking paradigm. The behavioral and growth findings confirm and extend the physiology data, and imply that in our rodent model, alpha-adrenergic mechanisms (including maternal vasoconstriction) are unlikely to mediate these toxic effects of transplacental cocaine exposure on developing brain. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anaesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kosofsky, BE (reprint author), Massachusetts Gen Hosp E, Lab Mol & Dev Neurosci, Bldg 149,CNY-2W,13th St, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA00175, DA08648] NR 40 TC 21 Z9 21 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 1998 VL 20 IS 3 BP 239 EP 249 DI 10.1016/S0892-0362(97)00128-1 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA ZU241 UT WOS:000074176500003 PM 9638681 ER PT J AU Roberts, SB Pi-Sunyer, FX Dreher, M Hahn, R Hill, JO Kleinman, RE Peters, JC Ravussin, E Rolls, BJ Yetley, E Booth, SL AF Roberts, SB Pi-Sunyer, FX Dreher, M Hahn, R Hill, JO Kleinman, RE Peters, JC Ravussin, E Rolls, BJ Yetley, E Booth, SL TI Physiology of fat replacement and fat reduction: Effects of dietary fat and fat substitutes on energy regulation SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Tufts-University Dialogue Conference on the Role of Fat-Modified Foods in Dietary Change CY DEC 07-09, 1997 CL TUFTS UNIV, BOSTON, MASSACHUSETTS SP Proctor & Gamble Co HO TUFTS UNIV ID HIGH-CARBOHYDRATE DIETS; EATING AD-LIBITUM; FREE-LIVING MEN; FOOD-INTAKE; WEIGHT-LOSS; SUCROSE POLYESTER; COVERT MANIPULATION; MACRONUTRIENT INTAKE; SUBSTRATE OXIDATION; CONTROLLED TRIAL C1 Tufts Univ, Boston, MA 02111 USA. Columbia Univ, St Lukes Roosevelt Hosp, New York, NY USA. Nabisco Foods Grp, E Hanover, NJ USA. Publ Voice Food & Hlth Policy, Washington, DC USA. Univ Colorado, Denver, CO 80202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Procter & Gamble Co, Cincinnati, OH USA. NIH, Phoenix, AZ USA. Penn State Univ, University Pk, PA 16802 USA. US FDA, Washington, DC 20204 USA. RP Booth, SL (reprint author), Tufts Univ, 711 Washington St, Boston, MA 02111 USA. NR 102 TC 35 Z9 36 U1 4 U2 5 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1998 VL 56 IS 5 BP S29 EP S41 PN 2 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZR336 UT WOS:000073963900004 PM 9624879 ER PT J AU Rosenberg Bieber Pi-Sunyer Leveille Roberts Denke Astrup Kennedy Kleinman Kristal Willett Dwyer Mela Marshall Blackburn Lichtenstein Hill Liebman Wing Peters Mendelson Sigman-Grant Haas AF Rosenberg Bieber Pi-Sunyer Leveille Roberts Denke Astrup Kennedy Kleinman Kristal Willett Dwyer Mela Marshall Blackburn Lichtenstein Hill Liebman Wing Peters Mendelson Sigman-Grant Haas TI Physiology of fat replacement and fat reduction: Effects of dietary fat and fat substitutes on energy regulation - Discussion SO NUTRITION REVIEWS LA English DT Editorial Material C1 Tufts Univ, Frances Stern Nutr Ctr, Boston, MA 02111 USA. Royal Vet & Agr Univ, Dept Human Nutr, Frederiksberg, Denmark. Best Foods, Somerset, NJ USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Georgetown Univ, Ctr Food & Nutr, Washington, DC USA. Univ Colorado, Denver, CO 80202 USA. USDA, Ctr Nutr Policy & Promot, Washington, DC 20250 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Ctr Sci Publ Interest, Washington, DC USA. Leveille Associates, Denville, NJ USA. Inst Food Res, Reading RG2 9AT, Berks, England. Ryerson Polytech Univ, Toronto, ON, Canada. Procter & Gamble Co, Cincinnati, OH USA. Arizona Canc Ctr, Tucson, AZ USA. Columbia Univ, St Lukes Roosevelt Hosp Ctr, New York, NY USA. Univ Nevada, Las Vegas, NV 89154 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Rosenberg (reprint author), Tufts Univ, Frances Stern Nutr Ctr, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1998 VL 56 IS 5 BP S41 EP S49 PN 2 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZR336 UT WOS:000073963900005 ER PT J AU Mantzoros, CS Liolios, AD Tritos, NA Kaklamani, VG Doulgerakis, DE Griveas, I Moses, AC Flier, JS AF Mantzoros, CS Liolios, AD Tritos, NA Kaklamani, VG Doulgerakis, DE Griveas, I Moses, AC Flier, JS TI Circulating insulin concentrations, smoking, and alcohol intake are important independent predictors of leptin in young healthy men SO OBESITY RESEARCH LA English DT Article DE leptin; obesity; insulin; smoking; alcohol; cortisol; growth hormone ID RESTING ENERGY-EXPENDITURE; LIGHT PHYSICAL-ACTIVITY; ISOLATED RAT ADIPOCYTES; CIGARETTE-SMOKING; PLASMA LEPTIN; OBESE GENE; BODY-WEIGHT; FOOD-INTAKE; OB PROTEIN; IN-VITRO AB Objective: Leptin, an adipocyte-secreted hormone, has been shown to signal the status of energy stores to the brain, regulate energy homeostasis, and mediate the neuroendocrine response to food deprivation. Obesity is associated with increased leptin levels, and several hormones, including insulin and glucocorticoids, have been associated with leptin levels and expression in rodents. Although obesity has been strongly associated with increased leptin in humans, a significant percentage of leptin's variability remains unexplained. The role of endogenous hormones, demographic factors, or certain life-style factors in explaining the residual variability of leptin levels has not yet been clarified. We performed this cross-sectional study to document the relative importance of obesity, lifestyle factor, and endogenous hormones in determining serum leptin levels. Research Methods and Procedures: We measured serum concentrations of insulin, cortisol, testosterone, growth hormone, and dehydroepiandrosterone sulfate; ascertained anthropometric, demographic, and lifestyle characteristics; and studied these variables in relationship to serum leptin concentrations in a sample of young healthy men. Results: Obesity and alcohol intake were independently and positively associated with circulating leptin concentrations. Additionally, cigarette smoking was negatively and independently associated with leptin concentrations. Finally, se rum insulin concentration was an independent hormonal determinant of circulating leptin concentrations, whereas serum testosterone was negatively associated with leptin only by bivariate analysis. Discussion: We conclude that, in addition to obesity, cigarette smoking, alcohol intake, and serum insulin levels are associated with leptin levels in a population of healthy young men. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02115 USA. Med Corps, Greek Army, Boston, MA 02115 USA. RP Flier, JS (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol, RN 324,330 Brookline Ave, Boston, MA 02115 USA. NR 68 TC 87 Z9 87 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 MAY PY 1998 VL 6 IS 3 BP 179 EP 186 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA ZN345 UT WOS:000073636600001 PM 9618121 ER PT J AU Goldberg, MF Dhaliwal, RS Olk, RJ AF Goldberg, MF Dhaliwal, RS Olk, RJ TI Indocyanine green angiography patterns of zones of relative decreased choroidal blood flow in patients with exudative age-related macular degeneration SO OPHTHALMIC SURGERY AND LASERS LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 06, 1994 CL SARASOTA, FLORIDA SP Assoc Res Vis & Ophthalmol ID CIRCULATION AB BACKGROUND AND OBJECTIVE: To investigate the incidence and patterns of posterior zones of relative decreased choroidal blood flow in patients with exudative age-related macular degeneration. PATIENTS AND METHODS: Digital indocyanine green (ICG) angiograms from 100 patients with exudative age-related macular degeneration were reviewed for the presence of posterior zones of relative decreased choroidal blood flow. The patterns of these zones and their location relative to the choroidal neovascular process were noted. RESULTS: Ninety-five percent of the angiograms displayed the presence of either a complete or an incomplete zone of relative choroidal hypoperfusion. The zone was most apparent in the early frames of the angiogram. Five different patterns of relative decreased choroidal blood flow were identified: horizontal (32%),vertical (14%), bipartite (9%),tripartite (31%), and quadripartite (9%). The choroidal neovascular process was located within or at the edge of the zone of relative choroidal hypoperfusion in all cases. CONCLUSION: Most cases of choroidal neovascularization localize to areas of relative choroidal dye nonfilling on ICG angiography. These patterns of choroidal nonfilling may have implications in the pathogenesis and management of choroidal neovascular membranes in age-related macular degeneration. C1 Washington Univ, Dept Ophthalmol, St Louis, MO 63110 USA. Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA USA. SE Retina Ctr, Augusta, GA USA. Queens Univ, Dept Ophthalmol, Kingston, ON, Canada. RP Olk, RJ (reprint author), Washington Univ, Dept Ophthalmol, 660 Euclid,Box 8096, St Louis, MO 63110 USA. NR 16 TC 5 Z9 6 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD MAY PY 1998 VL 29 IS 5 BP 385 EP 390 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA ZM520 UT WOS:000073548400004 PM 9599363 ER PT J AU Sperduto, RD Hiller, R Chew, E Seigel, D Blair, N Burton, TC Farber, MD Gragoudas, ES Haller, J Seddon, JM Yannuzzi, LA AF Sperduto, RD Hiller, R Chew, E Seigel, D Blair, N Burton, TC Farber, MD Gragoudas, ES Haller, J Seddon, JM Yannuzzi, LA TI Risk factors for hemiretinal vein occlusion: Comparison with risk factors for central and branch retinal vein occlusion - The eye disease case-control study SO OPHTHALMOLOGY LA English DT Article ID ALCOHOL-CONSUMPTION; CLINICAL-FEATURES; NATURAL-HISTORY; PATHOGENESIS AB Objective: Possible risk factors for hemiretinal vein occlusion were identified and compared with risk factor profiles for central and branch retinal vein occlusion. Design: The design was a multicenter case-control study. Methods: The authors identified 79 patients with hemiretinal vein occlusion (HRVO), 258 patients with central retinal vein occlusion (CRVO), 270 patients with branch retinal vein occlusion (BRVO), and 1142 control subjects at 5 clinical centers. Risk factor data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens. Results: Systemic hypertension and history of diabetes mellitus were associated with increased risk of HRVO. Risk of CRVO increased with history of diabetes, systemic hypertension, and higher erythrocyte sedimentation rate (females only); risk of CRVO decreased with increasing amounts of physical activity and increasing amounts of alcohol consumption. Systemic hypertension, higher body mass index, and higher alpha(2)-globulin levels were associated with increased risk of BRVO, whereas higher high-density lipoprotein levels and increasing levels of alcohol consumption were associated with decreased risk of BRVO. Glaucoma history was associated with all three types of retinal vein occlusion. Conclusion: Patients presenting with retinal vein occlusion should be evaluated for cardiovascular disease, diabetes, and glaucoma. C1 NEI, Div Biometry & Epidemiol, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Wilmer Eye Inst, Baltimore, MD USA. Manhattan Eye Ear & Throat Hosp, New York, NY 10021 USA. RP Sperduto, RD (reprint author), NEI, Div Biometry & Epidemiol, Bldg 31,Room 6A52,31 Center Dr,MSC 2510, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 EY999999]; NEI NIH HHS [N01-EY-5-2111, N01-EY-5-2109, N01-EY-5-2110] NR 21 TC 82 Z9 87 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1998 VL 105 IS 5 BP 765 EP 771 DI 10.1016/S0161-6420(98)95012-6 PG 7 WC Ophthalmology SC Ophthalmology GA ZL595 UT WOS:000073450100013 PM 9593373 ER PT J AU Shiuey, Y Lucarelli, MJ AF Shiuey, Y Lucarelli, MJ TI Traumatic hyphema - Outcomes of outpatient management SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 11-17, 1997 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID AMINOCAPROIC ACID; SECONDARY HEMORRHAGE AB Objective: This study aimed to compare the outcomes of outpatient and inpatient management of layered hyphema. Design: The charts of all patients with traumatic layered hyphema treated in the Massachusetts Eye and Ear Infirmary Emergency Ward between January 1991 and November 1995 were analyzed retrospectively. Patients with a diagnosis of microscopic hyphema, ruptured globe, or posterior segment injury other than commotio retinae on their initial emergency department visit were excluded. The study patients were compared with an historic control group of patients with hyphema who had been treated at the same institution from July 1986 to February 1989, Participants: A total of 154 patients met the study criteria. These were compared with 119 patients in the historic control group. Intervention: Of the study patients, 5% were admitted on the day of presentation, 95% were treated initially as outpatients, and 4% subsequently were admitted. All of the patients in the historic control group were treated with initial hospital admission. Main Outcome Measures: The rebleed rates of the study and control groups were compared. The final recorded visual acuity and causes of best-corrected visual acuity worse than 20/30 were analyzed for the study group. Results: The rebleed rates of the study group and the historic control group were 4.5% and 5.0%, respectively (P > 0.05). The rebleed rates of the study patients initially treated as outpatients and the historic control group were 3.4% and 5%, respectively (P > 0.05), The rebleed rates of study patients who did not receive aminocaproic acid and the subset of historic control patients who received aminocaproic acid were 3.3% and 4.8%, respectively (P > 0.05). Ninety-six percent of study patients achieved a final best-corrected visual acuity of 20/30 or better. Causes of a final documented visual acuity worse than 20/30 included loss of patient follow-up before resolution of the hyphema, traumatic cataract, macular hole, and macular degeneration. Conclusions: In the authors' predominantly white patient population, close outpatient follow-up of traumatic hyphemas appears to be safe and effective. Hospitalization for hyphema does not appear to decrease the rate of rebleeding. Decreased vision in the setting of traumatic hyphema generally results from comorbidities not affected by inpatient management. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. Massachusetts Eye & Ear Infirm, Eye Trauma Serv, Boston, MA 02114 USA. RP Shiuey, Y (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 22 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1998 VL 105 IS 5 BP 851 EP 855 DI 10.1016/S0161-6420(98)95025-4 PG 5 WC Ophthalmology SC Ophthalmology GA ZL595 UT WOS:000073450100026 PM 9593386 ER PT J AU Rubin, PAD Popham, J Rumelt, S Remulla, H Bilyk, JR Holds, J Mannor, G Maus, M Patrinely, JR AF Rubin, PAD Popham, J Rumelt, S Remulla, H Bilyk, JR Holds, J Mannor, G Maus, M Patrinely, JR TI Enhancement of the cosmetic and functional outcome of enucleation with the conical orbital implant SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of American-Academy-of-Ophthalmology CY OCT 29-NOV 02, 1995 CL ATLANTA, GEORGIA SP Amer Acad Ophthalmol ID ANOPHTHALMIC SOCKET; COMPUTED-TOMOGRAPHY; HYDROXYAPATITE; PATHOPHYSIOLOGY; ENOPHTHALMOS; SYSTEM AB Objective: The authors evaluated a new design of a conical-shaped enucleation implant to help minimize the occurrence of superior sulcus defects and maximize motility of the prosthesis. The implant shape is a modification of a sphere. It has a posterior conical projection paralleling the orbital walls, a superior projection supporting the soft tissues of the upper eyelid sulcus, a flattened anterior surface, and channels for each rectus muscle. Design: The study design was a consecutive case series from the Oculoplastics and Orbital Service of the Massachusetts Eye and Ear Infirmary. Intervention/Participants: A total of 45 patients (average age, 40 years; range, 13-75 years) had placement of a conical implant (39 primary enucleations, 6 secondary implants) with a minimum of 1 year' follow-up (range, 12-36 months). All of the primary enucleations and two of the secondary procedures had the anterior portion of the implant covered with autologous fascia. Four of the secondary implants were covered with pseudocapsule harvested from the explanted primary implant. Prostheses were fit 6 to 10 weeks after surgery. Main Outcome Measures: Postoperative appearance of patients was assessed by qualitative appearance of the superior sulcus and prosthetic motility, and subjectively by patients' satisfaction, Results: A total of 43 patients had minimal or no superior sulcus defect, whereas 2 patients had moderate defects. There were no severe sulcus defects. All patients were satisfied with their appearance and did not seek further surgery to correct any upper sulcus asymmetry. Prosthetic motility with small-angle ductions (<10 degrees) and saccades was good in all cases. There were two cases of conjunctival wound dehiscence. Both occurred within 4 weeks of surgery. One wound dehiscence was sutured, whereas the other healed spontaneously. There were no cases of implant extrusion, migration, or infection. Conclusion: The conical orbital implant provides appropriate reconstitution of orbital volume while minimizing superior sulcus defects with adequate prosthetic motility. C1 Massachusetts Eye & Ear Infirm, Dept Ophtalm Plast & Orbital Surg, Boston, MA 02114 USA. Colorado Ocuplast, Denver, CO USA. Thomas Jefferson Univ, Wills Eye Hosp, Dept Ophthalmol, Philadelphia, PA 19107 USA. St Louis Univ, Dept Ophthalmol, St Louis, MO 63103 USA. Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. Baylor Coll Med, Cullen Eye Inst, Houston, TX 77030 USA. RP Rubin, PAD (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophtalm Plast & Orbital Surg, Boston, MA 02114 USA. NR 18 TC 29 Z9 31 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1998 VL 105 IS 5 BP 919 EP 925 DI 10.1016/S0161-6420(98)95038-2 PG 7 WC Ophthalmology SC Ophthalmology GA ZL595 UT WOS:000073450100039 PM 9593398 ER PT J AU Crawford, WW Klaustermeyer, WB Lee, PH Placik, IM AF Crawford, WW Klaustermeyer, WB Lee, PH Placik, IM TI Comparative efficacy of terfenadine, loratadine, and astemizole in perennial allergic rhinitis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID DAYTIME SLEEPINESS; CHRONIC URTICARIA; CETIRIZINE; ANTIHISTAMINES; PERFORMANCE; PHARMACOKINETICS; DIPHENHYDRAMINE; HYDROXYZINE; MECHANISM; ALCOHOL AB Nonsedating H-1 antihistamines such as terfenadine, loratadine, and astemizole are widely prescribed for the treatment of allergic rhinitis. The comparative efficacy of these agents has not been thoroughly studied. We studied 14 subjects in an open-label four-way crossover trial. Patients were recruited from an outpatient allergy clinic. Inclusion criteria were documented rhinitis symptoms for at least 2 years before the study and skin-test positivity in response to perennial allergens. Each subject underwent sequential 2-week trials of each of four H-1 antihistamines: terfenadine, loratadine, astemizole, and chlorpheniramine, No placebo was included, Outcome measures were subjective rhinitis symptom scores, overall efficacy scores, and concomitant pseudoephedrine use, In addition, nasal-examination scores were obtained by way of physician assessment at the end of each 2-week trial, and side effects were tabulated. Nasal-examination scores for each of the four H-1 antihistamines were significantly better than the baseline scores (p < 0.05), No statistically significant differences in rhinitis symptom scores, overall efficacy scores, or concomitant pseudoephedrine use were noted. We detected no clinically significant differences in efficacy among terfenadine, loratadine, astemizole, and chlorpheniramine in the treatment of perennial allergic rhinitis. C1 W Los Angeles Vet Affairs Med Ctr, Allergy & Immunol Sect, Los Angeles, CA 90073 USA. RP Klaustermeyer, WB (reprint author), W Los Angeles Vet Affairs Med Ctr, Allergy & Immunol Sect, 111R,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 51 TC 11 Z9 11 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 1998 VL 118 IS 5 BP 668 EP 673 DI 10.1177/019459989811800517 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA ZM219 UT WOS:000073516600017 PM 9591867 ER PT J AU Bhattacharyya, N Wenokur, RK AF Bhattacharyya, N Wenokur, RK TI Endoscopic management of a chronic ethmoid and sphenoid sinus foreign body SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA USA. RP Bhattacharyya, N (reprint author), Joint Ctr Otolaryngol, 333 Longwood Ave, Boston, MA 02115 USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 1998 VL 118 IS 5 BP 687 EP 690 DI 10.1177/019459989811800523 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA ZM219 UT WOS:000073516600023 PM 9591873 ER PT J AU Mitsikostas, DD del Rio, MS Waeber, C Moskowitz, MA Cutrer, FM AF Mitsikostas, DD del Rio, MS Waeber, C Moskowitz, MA Cutrer, FM TI The NMDA receptor antagonist MK-801 reduces capsaicin-induced c-fos expression within rat trigeminal nucleus caudalis SO PAIN LA English DT Article DE N-methyl-D-aspartate; MK-801; trigeminal nucleus caudalis; inferior olive; pain; migraine ID METHYL-D-ASPARTATE; AMINO-ACID RECEPTORS; BRAIN-STEM NEURONS; SPINAL-CORD; DORSAL HORN; INTRACISTERNAL CAPSAICIN; CHEMICAL-STIMULATION; TRACTUS-SOLITARIUS; NITRIC-OXIDE; IMMUNOREACTIVITY AB The effect of the N-methyl-D-aspartate (NMDA) receptor antagonist (5R, 10S)-(+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine hydrogen maleate (MK-801) was examined on c-Sos-like immunoreactivity (c-fos-LI) in urethane-anesthetized Sprague-Dawley rats using a polyclonal antibody. C-Sos, an indicator of neuronal activation, was assessed within the trigeminal nucleus caudalis (TNC), area postrema, lateral reticular and solitary tract nuclei 2 h after intracisternal injection of capsaicin. C-fos-positive cells were counted at three representative levels corresponding to obex, -2.05 mm and -6.45 mm in IS tissue sections (50 mu m). A weighted average was obtained reflecting total brainstem expression within lamina I, II of TNC using a recently validated method. Capsaicin (0.1, 1, 5, 10 and 15 nmol) caused a dose-dependent labeling of cells in lamina I, II at obex similar to that previously reported after intracisternal blood or carrageenin administration in rats and guinea pigs. MK-801 (0.3, 1 and 3 mg/kg) administered i.p. 30 min before capsaicin (5 nmol in 100 mu l artificial CSF) reduced significantly and dose-dependently (12%, 36% and 47%, respectively) the c-Sos-LI cells in TNC at each level from rostral to caudal but not in solitary tract, area postrema and lateral reticular nuclei, and for unexplained reasons, increased c-Sos-LI within the inferior olive. These results suggest that NMDA receptors provide a potential therapeutic target for cephalic pain (e.g. migraine) due to trigeminovascular activation from meningeal afferents. (C) 1998 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Mitsikostas, DD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, 149 13th St,CNY-6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [NS 01803, NS 35611] NR 47 TC 87 Z9 92 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 1998 VL 76 IS 1-2 BP 239 EP 248 DI 10.1016/S0304-3959(98)00051-7 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA ZW322 UT WOS:000074398700028 PM 9696479 ER PT J AU Danis, CG Krebs, DE Gill-Body, KM Sahrmann, S AF Danis, CG Krebs, DE Gill-Body, KM Sahrmann, S TI Relationship between standing posture and stability SO PHYSICAL THERAPY LA English DT Article DE center of gravity; measurement; posture; stability; vestibular hypofunction ID BALANCE; POSITION AB Background and Purpose. This study determined whether persons with stability impairments have postural aberrations. We investigated whole-body posture and its relationship to center-of-gravity (COG) stability. Subjects. Data from 27 subjects with vestibular hypofunction and 26 subjects without vestibular impairment were analyzed. Method. An optoelectronic full-body system measured kinematics. Force plates measured ground reaction forces while subjects stood Ic idl their feet 30 cm apart and eyes open and with their feet together and eyes closed. Results. The subjects with vestibular hypofunction demonstrated less stability than the subjects without impairment, but there were no postural differences. Subjects with vestibular hypofunction had more weight on the left lower extremity during standing with feet apart. In all subjects in both groups, during standing with feet apart, the COG was anterior to the ankle, knee, back, and shoulder and posterior to the hip and neck. Subjects had an anterior pelvic tilt, extended trunk and head, right: laterally flexed trunk and pel iis, and flexed knees. With their feet together, subjects increased their anterior pelvic tilt; trunk, head, and knee flexion; and anterior COG position. Conclusion and Discussion. Posture and stability had a low correlation. Subjects with bilateral vestibular hypofunction did not demonstrate a forward head or backward trunk lean, as has been reported anecdotally. Changing from standing with feet apart to feet together increased whole-body movement patterns to control standing stability. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Washington Univ, Sch Med, Phys Therapy Program, St Louis, MO USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. EM krebs.david@mgh.harvard.edu FU NIA NIH HHS [R01AG11255]; PHS HHS [H133G60045] NR 35 TC 22 Z9 24 U1 0 U2 1 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD MAY PY 1998 VL 78 IS 5 BP 502 EP 517 PG 16 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA ZM234 UT WOS:000073518100006 PM 9597064 ER PT J AU Kubasek, WL Ausubel, FM Shirley, BW AF Kubasek, WL Ausubel, FM Shirley, BW TI A light-independent developmental mechanism potentiates flavonoid gene expression in Arabidopsis seedlings SO PLANT MOLECULAR BIOLOGY LA English DT Article DE Arabidopsis; flavonoid; seedling development; phenylalanine ammonia-lyase; chalcone synthase; chalcone isomerase; dihydroflavonol reductase ID MALATE SYNTHASE GENE; CHALCONE SYNTHASE; TRANSGENIC ARABIDOPSIS; ANTHOCYANIN PRODUCTION; BIOSYNTHESIS; THALIANA; CUCUMBER; MUTANTS; BLUE; PLANTS AB Throughout the plant kingdom expression of the flavonoid biosynthetic pathway is precisely regulated in response to developmental signals, nutrient status, and environmental stimuli such as light, heat and pathogen attack. Previously we showed that, in developing Arabidopsis seedlings, flavonoid genes are transiently expressed during germination in a light-dependent manner, with maximal mRNA levels occurring in 3-day-old seedlings. Here we describe the relationship between developmental and environmental regulation of flavonoid biosynthesis by examining phenylalanine ammonia-lyase (PAL), chalcone synthase (CHS), chalcone isomerase (CHI), and dihydroflavonol reductase (DFR) mRNA levels in germinating Arabidopsis seedlings as a function of light, developmental stage and temperature. We show that seedlings exhibit a transient potential for induction of these four genes, which is distinct from that observed for chlorophyll a/b-binding protein(CAB). The potential for flavonoid gene induction was similar in seedlings grown in darkness and red light, indicating that induction potential is not linked to cotyledon expansion or the development of photosynthetic capacity. The evidence for metabolic regulation of flavonoid genes during seedling development is discussed. C1 Virginia Polytech Inst & State Univ, Dept Biol, Blacksburg, VA 24061 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Shirley, BW (reprint author), Virginia Polytech Inst & State Univ, Dept Biol, Blacksburg, VA 24061 USA. RI Winkel, Brenda/A-6602-2008 OI Winkel, Brenda/0000-0003-3481-024X NR 45 TC 30 Z9 34 U1 0 U2 10 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 MAY PY 1998 VL 37 IS 2 BP 217 EP 223 DI 10.1023/A:1005977103116 PG 7 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA ZN588 UT WOS:000073660900003 PM 9617795 ER PT J AU Sims, CD Butler, PEM Cao, YL Casanova, R Randolph, MA Black, A Vacanti, CA Yaremchuk, MJ AF Sims, CD Butler, PEM Cao, YL Casanova, R Randolph, MA Black, A Vacanti, CA Yaremchuk, MJ TI Tissue engineered neocartilage using plasma derived polymer substrates and chondrocytes SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 6th Annual International Congress of Craniofacial Surgery CY OCT, 1995 CL ST TROPEZ, FRANCE AB This study demonstrates that fibrin monomers can be polymerized into moldable gels and used for the encapsulation of isolated chondrocytes. This biologically derived scaffold will maintain three-dimensional spatial support, allowing new tissue development in a subcutaneous space. Chondrocytes isolated from the glenohumeral and humeroradioulnar joints of a calf were combined with cyroprecipitate and polymerized with bovine thrombin to create a fibrin glue gel with a final cell density of 12.5 x 10(6) cells/ml. The polymer-chondrocyte constructs were implanted subcutaneously in 12 nude mice and incubated for 6 and 12 weeks in vivo. Histologic and biochemical analysis including deoxyribonucleic acid (DNA) and glycosaminoglycan quantitation confirmed the presence of actively proliferating chondrocytes with production of a well-formed cartilaginous matrix in the transplanted samples. Control specimens from 12 implantation sites consisting of chondrocytes alone or fibrin glue substrates did not demonstrate any gross or histologic evidence of neo-cartilage formation. Moldable autogenous fibrin glue polymer systems have a potential to serve as alternatives to current proprietary polymer systems used for tissue engineering cartilage as well as autogenous grafts and alloplastic materials used for facial skeletal and soft-tissue augmentation. C1 Massachusetts Gen Hosp, Div Plast Surg ACC 4, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. MIT, Dept Elect Engn, Cambridge, MA 02139 USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg ACC 4, 25 Fruit St, Boston, MA 02114 USA. NR 14 TC 138 Z9 171 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 1998 VL 101 IS 6 BP 1580 EP 1585 DI 10.1097/00006534-199805000-00022 PG 6 WC Surgery SC Surgery GA ZL347 UT WOS:000073423800022 PM 9583489 ER PT J AU Tosa, Y Lee, WPA Kollias, N Randolph, MA May, JW AF Tosa, Y Lee, WPA Kollias, N Randolph, MA May, JW TI Monoclonal antibody to intercellular adhesion molecule 1 protects skin flaps against ischemia-reperfusion injury: An experimental study in rats SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Surgery-of-the-Hand CY SEP 13-16, 1995 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Surg Hand ID NO-REFLOW PHENOMENON; SKELETAL-MUSCLE; REFLECTANCE SPECTROSCOPY; ADHERENCE REACTIONS; LEUKOCYTE ADHESION; MYOCUTANEOUS FLAP; MODEL; INFLAMMATION; PATHOGENESIS; SELECTIN AB The purpose of this study was to evaluate the blockage of polymorphonuclear neutrophil endothelial adhesion by using a monoclonal antibody to the intercellular adhesion molecule 1 (ICAM-1) ligand to prevent ischemia-reperfusion injury in rat skin flaps. A skin and subcutaneous tissue flap (3.0 cm x 4.5 cm) supplied by the superficial epigastric artery and vein including the femoral vessels was isolated unilaterally in 45 male Sprague-Dawley rats and clamped for 9 hours (groups II and III) or 12 hours (groups TV and V) of ischemia. Five animals in group I were sham-operated only with 5 minutes of ischemia. Animals in groups II (n = 10) and IV (n = 10) received 0.05 mg of monoclonal antibody to ICAM-1 (0.20 mg/kg) in 0.5 mi of 0.9% normal saline intravenously 15 minutes before reperfusion; those in groups III (n = 10) and V (n = 10) received 0.5 mi of normal saline. The flaps were assessed histologically, by measuring viable and nonviable areas, and by diffuse reflectance spectroscopy to determine the ratio of oxyhemoglobin to deoxyhemoglobin. Flap measurements revealed that the average area of flap survival was 90.6 +/- 12.8 percent in group II and 18.3 +/- 19.6 percent in the control group (III) (p < 0.002). In the animals subjected to 12 hours of ischemia, those treated with monoclonal antibody to ICAM-1 (group IV were 57.1 +/- 23.1 percent viable, which was significantly greater than the control animals (group V), in which only 0.3 +/- 1.0 percent of the flap was viable. Analysis of the diffuse reflectance spectra showed a hyperemic response during the first 10 minutes after reperfusion in animals treated with monoclonal antibody to ICAM-1. In group III, however, the spectra demonstrated a decreased amount of oxyhemoglobin, indicating decreased reperfusion of the flap after ischemia when compared with group II. Histopathologically, few inflammatory changes could be observed in groups I, II, and the viable areas of group IV. Marked damage was observed in groups III and Si. We concluded that treating ischemic skin flaps with monoclonal antibody to ICAM-1 was effective for alleviating reperfusion injury after 9 or 12 hours of warm ischemia. The reactive hyperemic response determined by diffuse reflectance spectroscopy in groups II and TV correlated with areas of flap survival. Antibodies to particular adhesion molecules, such as ICAM-1, have potential clinical utility in that they could be administered, individually or together, to patients immediately before reestablishing perfusion after free-tissue transfer or replantation to block the adverse effects attributed to reperfusion injury. C1 Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lee, WPA (reprint author), Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, WACC 453,55 Fruit St, Boston, MA 02114 USA. NR 39 TC 26 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 1998 VL 101 IS 6 BP 1586 EP 1594 DI 10.1097/00006534-199805000-00023 PG 9 WC Surgery SC Surgery GA ZL347 UT WOS:000073423800023 PM 9583490 ER PT J AU Starr, CE Guyer, DR Yannuzzi, LA AF Starr, CE Guyer, DR Yannuzzi, LA TI Age-related macular degeneration - Can we stem this worldwide public health crisis? SO POSTGRADUATE MEDICINE LA English DT Article ID SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; ANTIOXIDANTS; MACULOPATHY; PREVALENCE AB Age-related macular degeneration, the leading cause of legal blindness in people over age 60 worldwide, represents a public health crisis that deserves the attention and understanding of all physicians. The dry form of the disease is more common than the wet, but the wet form causes the most severe vision loss. Other than vision aids (eg, glasses, magnifiers), no treatments or preventive measures are currently available for patients with dry macular degeneration and laser photocoagulation with fluorescein angiography is the only clinically proven therapy for neovascular disease. Indocyanine green angiography is a promising new imaging tool that may improve detection of patients likely to benefit from laser therapy. Until better diagnostic and treatment options are available, early screening and patient education offer the best hope for reducing the widespread devastation caused by this disease. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Cornell Univ Med Coll, Ithaca, NY USA. Manhattan Eye Ear & Throat Hosp, New York, NY USA. Columbia Univ Coll Phys & Surg, New York, NY USA. RP Guyer, DR (reprint author), 519 E 72nd St,Suite 203, New York, NY 10021 USA. EM vrmny@aol.com NR 37 TC 15 Z9 15 U1 0 U2 1 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAY PY 1998 VL 103 IS 5 BP 153 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZL083 UT WOS:000073397100015 PM 9590992 ER PT J AU Luster, AD Cardiff, RD MacLean, JA Crowe, K Granstein, RD AF Luster, AD Cardiff, RD MacLean, JA Crowe, K Granstein, RD TI Delayed wound healing and disorganized neovascularization in transgenic mice expressing the IP-10 chemokine SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE chemokine; transgenic; wound healing ID INTERFERON-INDUCIBLE PROTEIN-10; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; X-C CHEMOKINE; IN-VIVO; KERATIN PROMOTER; EPIDERMAL-CELLS; SKIN; GENE; ANGIOGENESIS; INFLAMMATION AB IP-10 is a member of the or or cysteine-X amino acid-cysteine (CXC) chemokine family of chemotactic cytokines. High levels of IP-10 expression have been detected in a number of chronic human inflammatory conditions, including psoriasis, a common inflammatory disease of the skin. IP-10 has been shown to chemoattract activated T cells, inhibit the proliferation of endothelial cells, and inhibit the growth of tumors in vivo. To determine the capacity of IP-10 to modulate the inflammatory response in vivo, we have created transgenic mice that constitutively express IP-10 from keratinocytes. These mice developed normally and, in general, did not spontaneously recruit leukocytes into the skin or other organs that expressed the transgene. In addition, the transgenic mice had a normal cutaneous contact hypersensitivity cellular immune response. However, IP-10 transgenic mice had an abnormal wound healing response characterized by a more intense inflammatory phase and a prolonged and disorganized granulation phase with impaired blood vessel formation. These results have demonstrated that IP-10 can inhibit the neovascularization associated with a physiological response in vivo and have revealed a novel biologic activity of IP-10 as an inhibitor of wound healing. C1 Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Immunol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Allergy Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calif Davis, Dept Pathol, Davis, CA USA. Cornell Univ Med Coll, Dept Dermatol, New York, NY USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69212]; NIAMS NIH HHS [AR40667] NR 54 TC 91 Z9 92 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD MAY-JUN PY 1998 VL 110 IS 3 BP 183 EP 196 PG 14 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZU658 UT WOS:000074220200003 PM 9625525 ER PT J AU Tarazi, FI Yeghiayan, SK Neumeyer, JL Baldessarini, RJ AF Tarazi, FI Yeghiayan, SK Neumeyer, JL Baldessarini, RJ TI Medial prefrontal cortical D-2 and striatolimbic D-4 dopamine receptors: Common targets for typical and atypical antipsychotic drugs SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE antipsychotics, autoradiography, clozapine, dopamine receptors fluphenazine; S(+)-N-n-propylnorapomorphine ID CEREBRAL-CORTEX; RAT-BRAIN; SCHIZOPHRENIA; HALOPERIDOL; APOMORPHINE; STRIATUM; ISOMERS; BINDING; IDENTIFICATION; NEUROLEPTICS AB 1. In vitro receptor autoradiography was used to examine the long-term effects of a typical (fluphenazine), atypical (clozapine), or potential atypical antipsychotic (S[+]-N-n-propylnorapomorphine; [+]-NPA) on different dopamine (DA) receptor subtypes. 2. D(?)1-Like and D-3 receptor levels were not changed with any treatment in any brain region examined. 3. D-2 Receptors in caudate-putamen (CPu), nucleus accumbens (NAc) and olfactory tubercle (OT) were significantly increased by long-term treatment with fluphenazine, but not with clozapine or S[+]-NPA. 4. D-2 Receptor levels in medial prefrontal cortex (MPC), but not dorsolateral frontal cortex (DFC), were elevated after repeated daily administration of fluphenazine, clozapine, and S [+]-NPA. 5. D-4-Like receptors, assayed under D-4-selective conditions, were increased by fluphenazine, clozapine and S(+)-NPA in both NAc and CPu, but by none of these treatments in OT, DFC or MPC. 6. These results support a common role for medial prefrontal cortical D-2 and striatolimbic D-4 receptors in mediating the clinical actions of typical and atypical antipsychotic drugs. C1 Harvard Univ, Sch Med, Consolidated Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Program Neurosci, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Mailman Res Ctr, Belmont, MA USA. Massachusetts Gen Hosp, Alcohol & Drug Addict Res Ctr, McLean Div, Belmont, MA USA. RP Tarazi, FI (reprint author), Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. FU NIMH NIH HHS [MH-14275, MH-47370, MH-34006] NR 52 TC 24 Z9 24 U1 0 U2 0 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 MAY PY 1998 VL 22 IS 4 BP 693 EP 707 DI 10.1016/S0278-5846(98)00033-5 PG 15 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA ZQ703 UT WOS:000073894600009 PM 9682281 ER PT J AU McLellan, AT Hunkeler, E AF McLellan, AT Hunkeler, E TI Patient satisfaction and outcomes in alcohol and drug abuse treatment SO PSYCHIATRIC SERVICES LA English DT Article C1 Univ Penn, Dept Psychiat, Ctr Addict Studies, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Kaiser Permanente, Div Res, Oakland, CA USA. RP McLellan, AT (reprint author), Univ Penn, Dept Psychiat, Ctr Addict Studies, Bldg 7,Univ Ave, Philadelphia, PA 19104 USA. NR 9 TC 31 Z9 32 U1 0 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD MAY PY 1998 VL 49 IS 5 BP 573 EP 575 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA ZL567 UT WOS:000073447300002 PM 9603565 ER PT J AU Shaner, A Roberts, LJ Eckman, TA Racenstein, JM Tucker, DE Tsuang, JW Mintz, J AF Shaner, A Roberts, LJ Eckman, TA Racenstein, JM Tucker, DE Tsuang, JW Mintz, J TI Sources of diagnostic uncertainty for chronically psychotic cocaine abusers SO PSYCHIATRIC SERVICES LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 22-27, 1996 CL SAN JUAN, PUERTO RICO SP Coll Problems Drug Dependence ID SCHIZOPHRENIC-PATIENTS; AMPHETAMINE; DEXTROAMPHETAMINE; DISORDERS; SYMPTOMS; METHYLPHENIDATE AB Objective: This study determined the sources and frequency of diagnostic uncertainty for patients with chronic psychosis and active cocaine abuse or dependence and assessed the usefulness of prospective follow-up in clarifying diagnosis. Methods: A total of 165 male patients with chronic psychoses and cocaine abuse or dependence on inpatient units of a Veterans Affairs medical center were evaluated using the Structured Clinical Interview for DSM-III-R (SCID-R), urine tests, hospital records, and interviews with collateral sources. An algorithm allowing key SCID-R items and diagnostic criteria to be designated as provisionally met or uncertain was applied, resulting in a provisional diagnosis and a list of alternate diagnoses. The assessment was repeated 18 months later in an attempt to resolve diagnostic uncertainty. Results: In 30 cases (18 percent), initial assessment produced a definitive diagnosis, including 21 cases of schizophrenia, six of schizoaffective disorder, and three of psychostimulant-induced psychotic disorder In the other 135 cases, a definitive diagnosis could not be reached because of one or more soul ces of diagnostic uncertainty, including insufficient periods of abstinence (78 percent), poor memory (24 percent), and inconsistent reporting (20 percent). Reassessment at 18 months led to definitive diagnoses in 12 additional cases. Conclusions: It was frequently difficult to distinguish schizophrenia from chronic substance-induced psychoses. Rather than concluding prematurely that psychotic symptoms are, or are not, substance induced, clinicians should initiate treatment of both psychosis and the substance use disorder in uncertain cases. The persistence or resolution of psychosis during abstinence and additional history from the stabilized patient or collateral sources map clarify the diagnosis. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Shaner, A (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ashaner@ucla.edu FU NIMH NIH HHS [R01-MH48081] NR 37 TC 27 Z9 27 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD MAY PY 1998 VL 49 IS 5 BP 684 EP 690 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA ZL567 UT WOS:000073447300014 PM 9603577 ER PT J AU Stern, TA Cremens, MC AF Stern, TA Cremens, MC TI Factitious pheochromocytoma - One patient history and literature review SO PSYCHOSOMATICS LA English DT Article ID ILLNESS C1 Massachusetts Gen Hosp, Dept Psychiat, Psychiat Consultat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Stern, TA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Psychiat Consultat Serv, 100 Fruit St,WRN 605, Boston, MA 02114 USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1998 VL 39 IS 3 BP 283 EP 287 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA ZY261 UT WOS:000074602400007 PM 9664776 ER PT J AU Heckers, S Anick, D Boverman, JF Stern, TA AF Heckers, S Anick, D Boverman, JF Stern, TA TI Priapism following olanzapine administration in a patient with multiple sclerosis SO PSYCHOSOMATICS LA English DT Article ID DRUGS C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02214 USA. Harvard Univ, Sch Med, Avery D Weisman Psychiat Consultat Serv, Massachusetts Gen Hosp, Boston, MA 02214 USA. RP Heckers, S (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Warren 605,Fruit St, Boston, MA 02214 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 5 TC 14 Z9 14 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1998 VL 39 IS 3 BP 288 EP 290 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA ZY261 UT WOS:000074602400008 PM 9664777 ER PT J AU Lee, MJ Wittich, GR Mueller, PR AF Lee, MJ Wittich, GR Mueller, PR TI Percutaneous intervention in acute pancreatitis SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the Radiological-Society-of-North-America CY DEC 01-06, 1996 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE pancreas, abscess; pancreas, cysts; pancreas, interventional procedure; pancreas, necrosis; pancreatitis ID CATHETER DRAINAGE; FLUID COLLECTIONS; CLASSIFICATION-SYSTEM; PSEUDOCYSTS; MANAGEMENT; ABSCESSES; RADIOLOGIST; EXPERIENCE; ULTRASOUND; NECROSIS AB Interventional radiology has an important role to play in the management of local complications of acute pancreatitis, such as necrosis, pseudocyst, and abscess. Computed tomography (CT) is preferred for guiding pancreatic interventional procedures, with the most common access routes being through the left anterior pararenal space for pancreatic tail collections and through the gastrocolic ligament for pancreatic head and body collections. Pancreatic necrosis has a high mortality if infected, and the presence of infection must be determined with CT-guided needle aspiration, Careful planning of the access route is important to avoid the colon, Catheters of 8-12 F are usually sufficient for pseudocyst drainage. An average of 2-3 weeks drainage is required if there is no communication of the pseudocyst with the pancreatic duct and many weeks to months for pseudocysts with pancreatic duct communication, Percutaneous drainage of pseudocysts is associated with success rates of 80%-30%, Pancreatic abscess drainage has quoted success rates varying between 32% (infected necrosis) and 90% (pancreatic abscess). Use of large or multiple catheters is often required for complete drainage, The management of patients with severe acute pancreatitis is time-consuming and labor intensive for interventional radiologists, and a team approach with close communication with surgical personnel is required. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Texas, Med Branch, Dept Radiol, Galveston, TX 77550 USA. Beaumont Hosp, Dept Radiol, Dublin 9, Ireland. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 34 TC 26 Z9 29 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAY-JUN PY 1998 VL 18 IS 3 BP 711 EP 724 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZM744 UT WOS:000073571500013 PM 9599393 ER PT J AU Weissman, JL Curtin, HD Johnson, JT AF Weissman, JL Curtin, HD Johnson, JT TI Thyroid gland after total laryngectomy: CT appearance SO RADIOLOGY LA English DT Article DE larynx, neoplasms; thyroid; thyroid, CT ID CARCINOMA AB PURPOSE: To determine the computed tomographic (CT) appearance of the normal thyroid gland after total laryngectomy, because the high attenuation (or heterogeneous attenuation) of thyroid parenchyma was misinterpreted as tumor on several CT studies. MATERIALS AND METHODS: A search of computerized clinical files compiled from January 1996 through August 1997 yielded data on 24 patients who had undergone laryngectomy and subsequent CT of the neck. From these 24 patients, CT findings were available in 21. Because one patient had undergone total thyroidectomy and was excluded from the study, a retrospective review was performed in the remaining 20 patients. RESULTS: In 14 patients, unilateral thyroid tissue was present; in the other six there was bilateral thyroid tissue not connected by a isthmus. Thus, there were 26 remaining thyroid lobes, of which six were round and 20 were oval or lobular. Nineteen lobes showed homogeneously high attenuation (including one scanned without use of contrast material), six showed heterogeneous high attenuation or contained areas of hyperlucency, and one was obscured by streak artifact. CONCLUSION: Thyroid tissue can appear as unilateral or bilateral asymmetric masses on neck CT scans after laryngectomy. Gland tissue can show homogeneously or heterogeneously high attenuation. Familiarity with the varied postoperative appearance of normal thyroid gland can prevent its misdiagnosis as tumor. C1 Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Otolaryngol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Radiat Oncol, Pittsburgh, PA 15213 USA. Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Weissman, JL (reprint author), Univ Pittsburgh, Med Ctr, Dept Radiol, 200 Lothrop St,Room D132 PUH, Pittsburgh, PA 15213 USA. NR 9 TC 3 Z9 3 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1998 VL 207 IS 2 BP 405 EP 409 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ341 UT WOS:000073204300024 PM 9577488 ER PT J AU Aguilera-Tejero, E Lopez, I Estepa, JC Mayer-Valor, R Almaden, Y Concepcion, MT Felsenfeld, AJ Rodriguez, M AF Aguilera-Tejero, E Lopez, I Estepa, JC Mayer-Valor, R Almaden, Y Concepcion, MT Felsenfeld, AJ Rodriguez, M TI Mineral metabolism in healthy geriatric dogs SO RESEARCH IN VETERINARY SCIENCE LA English DT Article ID PARATHYROID-HORMONE; VITAMIN-D; RENAL-FAILURE; PHOSPHORUS; AGE; CALCITRIOL; CALCIUM; HYPERPARATHYROIDISM; RATS; 1,25-DIHYDROXYVITAMIN-D AB To study mineral metabolism in geriatric dogs, parathyroid hormone, calcitriol, ionised calcium, phosphorus, blood urea nitrogen and creatinine were evaluated in 35 geriatric dogs (> 10 years) and in 20 young adult dogs (2-5 years). Parathyroid hormone levels were within the normal range in both groups, but values (mean +/- SEM) were greater in the old dogs (34.8 +/- 3.6 vs 21.2 +/- 2.3 pg ml(-1), P=0.005). Calcitriol and ionised calcium were similar in the two groups, and the values for both parameters were within the normal reference range. Plasma phosphorus levels were in the normal range in both groups but tended to be greater in the older dogs (P=0.09). While blood urea nitrogen was similar in the two groups, creatinine levels (mean +/- SEM) were higher in the young dogs (82.2 +/- 3.5 vs 101.7 +/- 4.4 mu mol litre(-1)). Even when the dogs were matched for weight, plasma creatinine concentration was still greater in the younger dogs. In conclusion, an increase in parathyroid hormone without changes in calcium, phosphorus and calcitriol has been identified in geriatric dogs. C1 Univ Cordoba, Dept Patol Clin Vet, E-14071 Cordoba, Spain. Hosp Reina Sofia, Unidad Invest, Cordoba, Spain. Hosp Ntra Sra Candelaria, Tenerife, Spain. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Aguilera-Tejero, E (reprint author), Hosp Clin Vet, Campus Univ Rabanales,Ctra Madrid Cadiz Km 396, Cordoba 14014, Spain. RI Rodriguez, teresa/H-5452-2011 NR 25 TC 8 Z9 9 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0034-5288 J9 RES VET SCI JI Res. Vet. Sci. PD MAY-JUN PY 1998 VL 64 IS 3 BP 191 EP 194 DI 10.1016/S0034-5288(98)90123-0 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA ZZ911 UT WOS:000074781800003 PM 9690601 ER PT J AU Schumacher, HR AF Schumacher, HR TI Reactive arthritis SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID POLYMERASE CHAIN-REACTION; REITERS-SYNDROME; CHLAMYDIA-TRACHOMATIS; SYNOVIAL-MEMBRANE; YERSINIA-ENTEROCOLITICA; LYMPHOCYTES INDICATE; RHEUMATOID-ARTHRITIS; DOUBLE-BLIND; DISEASE; PLACEBO AB Concepts about reactive arthritis are changing and must embrace consideration of the fact that bacteria or their products are present in the joint, not just at the portal of entry in the gastrointestinal (GI) or genitourinary (GU) tracts. With chlamydia-associated disease, atypical elementary bodies can be seen in synovium by electron microscopy, and nucleic acids, including RNA, can be found. It is not yet clear if bacterial nucleic acids are present in postenteric reactive arthritis and whether disease courses are predictably different after GI or GU infection. How bacteria are disseminated to joints and local factors, including cytokines that influence their persistence, are under study. Treatment with antibiotics may help some chlamydia-associated reactive arthritis but is not invariably effective. C1 Vet Affairs Med Ctr, Arthritis Immunol Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Vet Affairs Med Ctr, Arthritis Immunol Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NIAMS NIH HHS [AR-42541] NR 90 TC 28 Z9 29 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 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD MAY PY 1998 VL 24 IS 2 BP 261 EP + DI 10.1016/S0889-857X(05)70008-9 PG 14 WC Rheumatology SC Rheumatology GA ZN735 UT WOS:000073676700005 PM 9606758 ER PT J AU Sorenson, AG AF Sorenson, AG TI Diffusion/perfusion MR imaging in acute stroke SO RIVISTA DI NEURORADIOLOGIA LA English DT Article; Proceedings Paper CT Symposium Neuroradiologicum XVI (SNR XVI) CY MAY 15-17, 1998 CL PHILADELPHIA, PENNSYLVANIA AB This presentation will address using MRI for acute Stroke imaging in a clinical setting, with some discussion of the insights clinical observations are yielding about basic science mechanisms of stroke pathophysiology. A few pertinent technical aspects of diffusion and perfusion imaging will be mentioned in a brief "how-I-do-it" fashion, including how to fit imaging acute stroke patients into a busy clinical MRI service. In addition to insights "routine" DWI/PWI are yielding into the depiction and evolution of a probable ischemic penumbra, new techniques such as diffusion tensor anisotropy and mapping of tissue mean transit time will be discussed. Brief examples of application of these techniques to other cerebrovascular diseases will be given. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI CENTAURO PI BOLOGNA PA VIA DEL PRATELLO, 8, 40122 BOLOGNA, ITALY SN 1120-9976 J9 RIV NEURORADIOL JI Riv. Neuroradiol. PD MAY PY 1998 VL 11 SU 1 BP 59 EP 60 PG 2 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZT755 UT WOS:000074122400009 ER PT J AU Curtin, HD AF Curtin, HD TI Staging of nodale disease SO RIVISTA DI NEURORADIOLOGIA LA English DT Article; Proceedings Paper CT Symposium Neuroradiologicum XVI (SNR XVI) CY MAY 15-17, 1998 CL PHILADELPHIA, PENNSYLVANIA ID CERVICAL LYMPH-NODES; CT; NECK; METASTASIS; CARCINOMA; CRITERIA; CANCER AB Metastases to lymph nodes from head and neck cancer is considered an important indicator of prognosis. Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and Ultrasound have all been used in an effort to more accurately define the status of the neck nodes. All are considered more accurate than clinical palpation. The use of imaging modalities to stage the neck will be described, along with newer experimental techniques that hold promise for staging of the neck nodes. The importance of negative predictive values in determining the usefulness of a particular imaging modality will be emphasized. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU EDIZIONI CENTAURO PI BOLOGNA PA VIA DEL PRATELLO, 8, 40122 BOLOGNA, ITALY SN 1120-9976 J9 RIV NEURORADIOL JI Riv. Neuroradiol. PD MAY PY 1998 VL 11 SU 1 BP 74 EP 77 PG 4 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZT755 UT WOS:000074122400016 ER PT J AU Netscher, DT Cohen, V AF Netscher, DT Cohen, V TI Ulnar nerve entrapment at the wrist: Cases from a hand surgery practice SO SOUTHERN MEDICAL JOURNAL LA English DT Article AB Background. Eight patients with 11 instances of wrist-level ulnar nerve entrapment, a fairly uncommon compression syndrome, were identified in a hand surgery practice from 1992 through 1996. Methods. Presentations, causes, and surgical outcomes were examined, and the pertinent literature was reviewed. Results. All eight patients had extrinsic, nonidiopathic compression of the ulnar nerve caused by tumor, vascular disease, anomalous muscle development, or a tight fibrous arch at the origin of the flexor digiti minimi. In all cases, sensory symptoms resolved with removal of the cause of ulnar nerve compression. Conclusions. These cases serve to remind physicians that not every instance of numbness and tingling in the hand represents carpal tunnel syndrome. Careful clinical examination may not only localize compression of the ulnar nerve at wrist level but also may reveal its etiology. Some causes of ulnar compressive neuropathy, however, are apparent only with surgical exploration. 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 24 TC 9 Z9 12 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD MAY PY 1998 VL 91 IS 5 BP 451 EP 456 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZM757 UT WOS:000073572800008 PM 9598853 ER PT J AU Sazon, DA Hoo, GWS Santiago, S AF Sazon, DA Hoo, GWS Santiago, S TI Hemoptysis as the sole presentation of Pasteurella multocida infection SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID PNEUMONIA AB Pasteurella multocida has been implicated as the cause of a variety of respiratory conditions leg, bronchitis, pneumonia, lung abscess, empyema), but hemoptysis has been noted only in conjunction with other lung conditions. We report a case in which hemoptysis was the sole manifestation of Pasteurella infection. The patient was a middle-aged man with severe obstructive lung disease and exposure to cats. Diagnosis was made by bronchoscopy and high-dose penicillin was required for resolution. C1 W Los Angeles Vet Affairs Med Ctr, Pulm & Crit Care Sect 111Q, Los Angeles, CA 90703 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Hoo, GWS (reprint author), W Los Angeles Vet Affairs Med Ctr, Pulm & Crit Care Sect 111Q, 11301 Wilshire Blvd, Los Angeles, CA 90703 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD MAY PY 1998 VL 91 IS 5 BP 484 EP 486 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA ZM757 UT WOS:000073572800017 PM 9598862 ER PT J AU Rordorf, G Koroshetz, WJ Copen, WA Cramer, SC Schaefer, PW Budzik, RF Schwamm, LH Buonanno, F Sorensen, AG Gonzalez, G AF Rordorf, G Koroshetz, WJ Copen, WA Cramer, SC Schaefer, PW Budzik, RF Schwamm, LH Buonanno, F Sorensen, AG Gonzalez, G TI Regional ischemia and ischemic injury in patients with acute middle cerebral artery stroke as defined by early diffusion-weighted and perfusion-weighted MRI SO STROKE LA English DT Article DE middle cerebral artery; stroke; magnetic resonance imaging; diffusion-weighted imaging; perfusion-weighted imaging ID THRESHOLDS; PENUMBRA AB Background and Purpose-We sought to map early regional ischemia and infarction in patients with middle cerebral artery (MCA) stroke and compare them with final infarct size using advanced MRI techniques, MRT can now delineate very early infarction by diffusion-weighted imaging (DWI) and abnormal tissue perfusion by perfusion-weighted imaging (PWI). Methods-Seventeen patients seen within 12 hours of onset of MCA stroke had MR angiography, standard MRI, and PWI and DWI MRI. PWI maps were generated by analysis of the passage of intravenous contrast bolus through the brain. Cerebral blood volume (CBV) was determined after quantitative analysis of PWI data, Volumes of the initial DWI and PWI lesion were calculated and compared with a final infarct volume from a follow-up imaging study (CT scan or MRI), Results-Group 1 (10 patients) had MCA stem (M1) occlusion by MR angiography. DWI lesion volumes were smaller than the volumes of CBV abnormality. In 7 patients the final stroke volume was larger or the same, and in 3 it was smaller than the initial CBV lesion. Group 2 (7 patients) had an open M1 on MR angiography with distal MCA stroke. In 6 group 2 patients, the initial DWI lesion matched the initial CBV abnormality and the final infarct. Conclusions-Most patients with M1 occlusion showed progression of infarction into the region of abnormal perfusion. In contrast, patients with open M1 had strokes consistent with distal branch occlusion and had maximal extent of injury on DWI at initial presentation, Application of these MRI techniques should improve definition of different acute stroke syndromes and facilitate clinical decision making. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. RP Rordorf, G (reprint author), Massachusetts Gen Hosp, Dept Neurol, BLK 1291,Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 NR 11 TC 182 Z9 189 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 1998 VL 29 IS 5 BP 939 EP 943 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZN073 UT WOS:000073606000011 PM 9596239 ER PT J AU Spitzer, TR Grunberg, SM Dicato, MA AF Spitzer, TR Grunberg, SM Dicato, MA TI Antiemetic strategies for high-dose chemoradiotherapy-induced nausea and vomiting SO SUPPORTIVE CARE IN CANCER LA English DT Article; Proceedings Paper CT MASCC Consensus Conference on Antiemetic Therapy CY APR 28-29, 1997 CL PERUGIA, ITALY DE bone marrow transplantation; irradiation; chemotherapy; emesis; antiemetic therapy ID TOTAL-BODY IRRADIATION; BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; DOUBLE-BLIND; INDUCED EMESIS; ONDANSETRON; CHEMOTHERAPY; PREVENTION; PROPHYLAXIS; GRANISETRON AB The treatment of nausea and vomiting in patients receiving high doses of irradiation and/or chemotherapeutic agents as preparation for hematopoietic stem cell transplantation is discussed. Such patients have very high rates of both early and delayed emesis. Based on the available evidence it is recommended that 5-MT3 receptor antagonists be used to combat emesis in this setting. Continued research is also required to define the optimal antiemetic strategy for these patients. C1 Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Program, Boston, MA 02114 USA. Univ Vermont, Dept Med & Pharmacol, Burlington, VT USA. Ctr Hosp, L-1210 Luxembourg, Luxembourg. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Program, Boston, MA 02114 USA. NR 16 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAY PY 1998 VL 6 IS 3 BP 233 EP 236 DI 10.1007/s005200050159 PG 4 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA ZN172 UT WOS:000073617100009 PM 9629875 ER PT J AU Zittel, TT Lloyd, KC Rothenhofer, I Wong, H Walsh, JH Raybould, HE AF Zittel, TT Lloyd, KC Rothenhofer, I Wong, H Walsh, JH Raybould, HE TI Calcitonin gene-related peptide and spinal afferents partly mediate postoperative colonic ileus in the rat SO SURGERY LA English DT Article ID SUBSTANCE-P; INHIBITORY REFLEX; SENSORY NEURONS; SOLITARY TRACT; GASTRIC ILEUS; DORSAL HORN; CAPSAICIN; CGRP; SOMATOSTATIN; SURGERY AB Background. Calcitonin gene-related peptide (CGRP) is a widely distributed neuropeptide contained in intrinsic and extrinsic neurons of the gastrointestinal wall that has been shown to be released by noxious stimulation, to be involved in nociception, to inhibit gastrointestinal motility and to partly mediate postoperative gastric ileus. Mie hypothesized that abdominal surgery-induced release of CGRP might inhibit postoperative colonic motility and food intake. Methods. Colonic transit, stool pellet number stool pellet weight, and food intake were measured for 48 hours after induction of postoperative ileus in rats. CGRP was immunoneutralized by preoperative injection of CGRP monoclonal antibody, or visceral afferent nerve fibers containing CGRP were functionally ablated by topical capsaicin treatment of the vagus nerves or of the celiac/superior mesenteric ganglia before abdominal surgery. Result. Abdominal surgery increased colonic transit time and decreased 24-hour cumulative stool pellet number stool pellet weight, and food intake. CGRP immunoneutralization reversed postoperative inhibition of colonic colonic transit, 24-hour cumulative stool pellet number; stool pellet weight, and food intake by 77%, 82%, 80%, and 52%, respectively. Whereas ablation of vagal afferent nerve fibers had no effect, spinal afferent nerve fiber ablation reversed postoperative inhibition of 24-hour cumulative stool pellet number stool pellet weight, and food intakes by 41%, 38%, and 19%, respectively. Conclusions. CGRP and spinal afferent nerve fibers partly mediate postoperative colonic ileus and inhibition of food intakes in the rat. By the magnitude of reversal of postoperative ileus; CGRP seems to be an important mediator of postoperative colonic ileus. Our results for the first time show involvement of a neuropeptide and spinal afferents in the mediation of postoperative colonic ileus and postoperative inhibition of food intake in rats. C1 Univ Tubingen, Dept Abdominal & Transplantat Surg, Chirurg Klin, Allgemeinchirurg Abt, D-72076 Tubingen, Germany. W Los Angeles Vet Affairs Med Ctr, Gastroenter Biol Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Zittel, TT (reprint author), Univ Tubingen, Dept Abdominal & Transplantat Surg, Chirurg Klin, Allgemeinchirurg Abt, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. NR 47 TC 54 Z9 55 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 1998 VL 123 IS 5 BP 518 EP 527 DI 10.1067/msy.1998.88090 PG 10 WC Surgery SC Surgery GA ZL762 UT WOS:000073468800005 PM 9591004 ER PT J AU Torre-Amione, G MacLellan, W Kapadia, S Weilbaecher, D Farmer, J Young, J Mann, D AF Torre-Amione, G MacLellan, W Kapadia, S Weilbaecher, D Farmer, J Young, J Mann, D TI Tumor necrosis factor-alpha is persistently expressed in cardiac allografts in the absence of histological or clinical evidence of rejection SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT 1st International Symposium on Assessment of Acute Rejection and Allograft Coronary Disease CY JUL 11-12, 1997 CL THUN, SWITZERLAND ID FACTOR RECEPTORS; HEART; CYTOKINES; MYOCARDIUM C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Methodist Hosp, Ctr Multiorgan Transplant, Houston, TX 77030 USA. RP Torre-Amione, G (reprint author), Baylor Coll Med, VA Med Ctr, SM1246,6550 Fannin, Houston, TX 77030 USA. NR 18 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD MAY PY 1998 VL 30 IS 3 BP 875 EP 877 DI 10.1016/S0041-1345(98)00083-9 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZM172 UT WOS:000073511900079 PM 9595133 ER PT J AU Tootell, RBH Hadjikhani, NK Mendola, JD Marrett, S Dale, AM AF Tootell, RBH Hadjikhani, NK Mendola, JD Marrett, S Dale, AM TI From retinotopy to recognition: fMRI in human visual cortex SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID POSITRON EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; INFERIOR TEMPORAL CORTEX; HUMAN BRAIN; SELECTIVE ATTENTION; FUNCTIONAL MRI; NEURAL MECHANISMS; HIPPOCAMPAL-FORMATION; SENSORY STIMULATION; PREFRONTAL CORTEX AB Recent advances in functional magnetic resonance imaging (fMRI) have furnished increasingly informative and accurate maps of the retinotopy and functional organization in human visual cortex. Here we review how information in those sensory-based maps is topographically related to, and influenced by, more cognitive visuo-spatial dimensions, such as mental imagery, spatial attention, repetition effects and sire perception. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02129 USA. RP Tootell, RBH (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, 149 13th St, Boston, MA 02129 USA. EM tootell@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Hadjikhani, Nouchine/C-2018-2008; OI Hadjikhani, Nouchine/0000-0003-4075-3106; Marrett, Sean/0000-0001-8179-6511 NR 82 TC 131 Z9 131 U1 0 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD MAY PY 1998 VL 2 IS 5 BP 174 EP 183 DI 10.1016/S1364-6613(98)01171-1 PG 10 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 171NZ UT WOS:000078871300005 PM 21227152 ER PT J AU Dickersin, GR Scully, RE AF Dickersin, GR Scully, RE TI Ovarian small cell tumors: An electron microscopic review SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE electron microscopy; ovary; small cell tumors ID CLINICOPATHOLOGICAL ANALYSIS; NEUROECTODERMAL TUMOR; HYPERCALCEMIC TYPE; CARCINOMA; LYMPHOMAS AB Small cell tumors of the ovary are uncommon but represent an important group to recognize in the differential diagnosis of primary and metastatic ovarian neoplasms. In some cases the correct diagnosis cannot be confidently made on the basis of clinical setting, routine light microscopy, and immunohistochemistry, and electron microscopy may be supportive or definitive in establishing cell type. The cell type is often important in choosing optimal therapy and in predicting prognosis. The authors performed electron microscopy on a moderate number of ovarian small cell tumors and here describe and illustrate the diagnostic features of representative examples of various types. The ultrastructural features of the metastatic tumors, such as embryonal rhabdomyosarcoma, neuroblastoma, and melanoma, are identical to those of their respective primary tumors, are well known, and usually pose no problem in diagnosis. On the other hand, the ultrastructural features of some primary ovarian small cell tumors may present a more difficult differential diagnosis, because they have features that are subtle and/or in common. Exemplary of tumors in this category are diffuse adult granulosa cell tumor, endometrial stromal sarcoma, and small cell carcinomas of the hypercalcemic and pulmonary (oat cell) types. Distinguishing among them may be difficult but is possible, and electron microscopy may be a valuable supplement to the diagnostic information obtained from the clinical presentation, light microscopy, immunohistochemistry and, in some tumors, cytometric analysis of these neoplasms. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Dickersin, GR (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 100 Blossom St,Cox 5, Boston, MA 02114 USA. NR 31 TC 14 Z9 15 U1 0 U2 1 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD MAY-JUN PY 1998 VL 22 IS 3 BP 199 EP 226 PG 28 WC Microscopy; Pathology SC Microscopy; Pathology GA 126FZ UT WOS:000076283600004 PM 9793201 ER PT J AU Maluf, HM Koerner, FC Dickersin, GR AF Maluf, HM Koerner, FC Dickersin, GR TI Collagenous spherulosis: An ultrastructural study SO ULTRASTRUCTURAL PATHOLOGY LA English DT Article DE basement membrane; collagenous spherulosis; sclerosing adenosis ID BREAST AB Ultrastructural findings are described in two cases of collagenous spherulosis associated with intraductal hyperplasia and sclerosing adenosis. The spherules showed a variable composition of basement membrane, banded collagen, and mineral deposition. Some spherules were connected to the periacinal stroma by a thin pedicle. The authors propose that spherules represent a peculiar form of stromal invagination that could be seen in a variety of breast lesions, rather than a form of intraductal hyperplasia. C1 Univ Tennessee, Dept Pathol, Memphis, TN USA. Massachusetts Gen Hosp, James Homer Wright Pathol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Maluf, HM (reprint author), Washington Univ, Sch Med, Div Surg Pathol, 660 S Euclid Ave, St Louis, MO 63110 USA. NR 13 TC 4 Z9 4 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0191-3123 J9 ULTRASTRUCT PATHOL JI Ultrastruct. Pathol. PD MAY-JUN PY 1998 VL 22 IS 3 BP 239 EP 248 PG 10 WC Microscopy; Pathology SC Microscopy; Pathology GA 126FZ UT WOS:000076283600007 PM 9793204 ER PT J AU Geissler, M Tokushige, K Wakita, T Zurawski, VR Wands, JR AF Geissler, M Tokushige, K Wakita, T Zurawski, VR Wands, JR TI Differential cellular and humoral immune responses to HCV core and HBV envelope proteins after genetic immunizations using chimeric constructs SO VACCINE LA English DT Article DE helper T cells; cytokines; antibody; secretion ID HEPATITIS-B VIRUS; SURFACE-ANTIGEN PARTICLES; MONOCLONAL-ANTIBODIES; DNA VACCINATION; T-LYMPHOCYTES; RABIES VIRUS; INFECTION; MICE; INDUCTION; CELLS AB Development of a broad based cellular and humoral immune response to hepatitis C virus (HCV) structural proteins may be important for eradication of viral infection. In previous studies in mice we demonstrated that facilitated DNA-based immunization with an HCV core DNA-expression construct stimulated the generation of weak cytotoxic T lymphocyte (CTL), helper T cell (Th), and humoral immune responses against HCV core related epitopes. To enhance the immunogenicity of the non-secreted viral structural protein at both the B- and T-cell level, several chimeric HBV-HCV constructs were prepared which were designed to express and secrete HCV core protein along with various regions of the hepatitis B envelope protein. No secretion of the chimeric proteins into the culture supernatant was detected using sensitive radio-immunoassays, However such chimeric proteins were capable of generating CD4+ inflammatory T cell and CD8+ CTL activity against both HBV and HCV components of the fusion proteins. It was determined that the proliferative activity of T cells as well as the humoral immune responses to HCV core protein were substantially enhanced by some chimeric fusion proteins as compared to the HCV core protein alone. The strength of the immune responses appeared directly related to the level of Th1 cytokines produced by CD4+ T cells obtained from immunized animals, Further characterization of the immune responses stimulated by these DNA constructs studied helped to define some of the most immunogenic regions of the chimeric proteins that they encode. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Freiburg, Med Klin 2, D-79106 Freiburg, Germany. Massachusetts Gen Hosp, Ctr Canc, Mol Hepatol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Tokyo Womens Med Coll, Shinjuku Ku, Tokyo 162, Japan. Tokyo Metropolitan Inst Med Sci, Bunkyo Ku, Tokyo 113, Japan. Apollon Inc, Malvern, PA 19355 USA. RP Geissler, M (reprint author), Univ Freiburg, Med Klin 2, Labor B3,Hugstetter Str 55, D-79106 Freiburg, Germany. EM mgeissl@ukl.uni-freiburg.de FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02169] NR 43 TC 43 Z9 47 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY PY 1998 VL 16 IS 8 BP 857 EP 867 DI 10.1016/S0264-410X(97)00236-3 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZP179 UT WOS:000073725300013 PM 9627944 ER PT J AU Tasker, SA O'Brien, WA Treanor, JJ Weiss, PJ Olson, PE Kaplan, AH Wallace, MR AF Tasker, SA O'Brien, WA Treanor, JJ Weiss, PJ Olson, PE Kaplan, AH Wallace, MR TI Effects of influenza vaccination in HIV-infected adults: a double-blind, placebo-controlled trial SO VACCINE LA English DT Article DE HIV infection; influenza vaccination; quantitative HIV-1 RNA measurement; CD4 lymphocytes ID IMMUNODEFICIENCY-VIRUS INFECTION; ANTIBODY-RESPONSES; IMMUNIZATION; REPLICATION; TYPE-1; ACTIVATION; PLASMA; INDIVIDUALS; LYMPHOCYTES; CHILDREN AB Annual influenza vaccine is recommended for persons with HIV infection, Recent reports indicate that immunizations may increase HII replication in infected individuals, Forty-seven HIV-infected patients were randomized to influenza vaccine or saline placebo using a double blind study design, One month after-vaccination, plasma HIV-I RNA increased in the vaccinated but not placebo group (p=0.029) At 3 months, CD4% dropped an average of 1.6 points in the vaccinated group compared to an increase of 0.1 points in the placebo group (p = 0.039), Patients on stable antiretroviral regimens had CD4% drop an average of 2.3 points in the vaccinated group at 3 months versus 0.1 points in the placebo group (p = 0.015), It is concluded that HIV-infected patients are at risk for increased HIV replication and decreases in CD4% following influenza vaccination. Since influenza has not been associated with significant morbidity in this population, further study of routine influenza vaccination for HIV-infected patients is warranted. (C) 1998 Published by Elsevier-Science Ltd. All rights reserved. C1 USN, Med Ctr, Dept Internal Med, Div Infect Dis, San Diego, CA 92134 USA. USN, Med Ctr, Div Clin Invest, San Diego, CA 92134 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Rochester, Med Ctr, Infect Dis Unit, Rochester, NY 14627 USA. USN, Med Ctr, Environm & Prevent Med Unit 5, San Diego, CA 92134 USA. Univ Calif Los Angeles, Sch Med, Dept Immunol & Microbiol, Los Angeles, CA 90024 USA. RP Tasker, SA (reprint author), USN, Med Ctr, Dept Internal Med, Div Infect Dis, 34800 Bob Wilson Dr, San Diego, CA 92134 USA. NR 31 TC 70 Z9 76 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY-JUN PY 1998 VL 16 IS 9-10 BP 1039 EP 1042 DI 10.1016/S0264-410X(97)00275-2 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZV083 UT WOS:000074266800028 PM 9682356 ER PT J AU de Virgilio, C Kirby, L Lewis, RJ Donayre, C Baker, JD White, R Stabile, BE AF de Virgilio, C Kirby, L Lewis, RJ Donayre, C Baker, JD White, R Stabile, BE TI Limited utility of dipyridamole-thallium for predicting adverse cardiac events after vascular surgery SO VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 68th Annual Session of the Pacific-Coast-Surgical-Association CY FEB 15-19, 1997 CL NAPA, CALIFORNIA SP Pacific Coast Surg Assoc ID PREOPERATIVE ASSESSMENT; SCINTIGRAPHY; RISK AB The objective of this retrospective study was to determine the value of dipyridamole-thallium (PTHAL) and Eagle criteria (Q wave on EGG, ventricular ectopy, diabetes, congestive heart failure, age greater than or equal to 70, angina) in predicting cardiac events after vascular surgery at a Veteran Affairs hospital. The main outcome measures were adverse cardiac events. Of 211 vascular procedures, 148 were performed without, and 63 performed with, preoperative PTHAL. Thirty-six patients had redistribution on PTHAL, but only two underwent preoperative coronary revascularization. There were 10 cardiac events (4.8%), five in each group (p=NS). Cardiac events were increased with greater than or equal to one Eagle criteria (6.7% vs 0% with no Eagle, p=0.04), but not with PTHAL redistribution. Conclusions: Prior to elective vascular surgery: (1) PTHAL redistribution did not predict cardiac events. (2) Cardiac morbidity was increased with greater than or equal to one Eagle criteria. (3) Cardiac testing is not indicated in patients without Eagle criteria. C1 W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA 90073 USA. RP de Virgilio, C (reprint author), Univ Calif Los Angeles, Harbor Med Ctr, Div Vasc Surg, Box 25,1000 W Carson St, Torrance, CA 90509 USA. NR 7 TC 10 Z9 10 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 0042-2835 J9 VASCULAR SURG JI Vasc. Surg. PD MAY-JUN PY 1998 VL 32 IS 3 BP 275 EP 279 DI 10.1177/153857449803200316 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA ZN744 UT WOS:000073677700014 ER PT J AU Haines, DC Gorelick, PL Battles, JK Pike, KM Anderson, RJ Fox, JG Taylor, NS Shen, Z Dewhirst, FE Anver, MR Ward, JM AF Haines, DC Gorelick, PL Battles, JK Pike, KM Anderson, RJ Fox, JG Taylor, NS Shen, Z Dewhirst, FE Anver, MR Ward, JM TI Inflammatory large bowel disease in immunodeficient rats naturally and experimentally infected with Helicobacter bilis SO VETERINARY PATHOLOGY LA English DT Article DE colitis; Helicobacter; nude rats; typhlitis ID CHRONIC ACTIVE HEPATITIS; SP-NOV; CAMPYLOBACTER-CINAEDI; BACTERIAL-INFECTION; MACACA-NEMESTRINA; GASTRIC-CARCINOMA; PYLORI GASTRITIS; HOMOSEXUAL MEN; ANIMAL-MODEL; SCID MICE AB Proliferative and ulcerative typhlitis, colitis, and proctitis were found incidentally in a breeding colony of male athymic nude (Cr:NIH-rnu) rats. Within the crypts of the large intestine, modified Steiner's silver stain revealed spiral organisms that were identified by culture, polymerase chain reaction, and sequencing to be Helicobacter bills. The large bowel disease was reproduced in H. bilis-free male athymic nude rats that were injected intraperitoneally with a culture of H. bilis from the affected colony. The organism was isolated from the feces and cecum of the experimentally infected rats. H. bilis should be considered a potential pathogen in immunocompromised rats. The infection in immunocompromised rats may serve as an animal model for inflammatory large bowel disease. C1 NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Off Lab Anim Resources,Div Basic Sci,FCRDC, Frederick, MD 21702 USA. NCI, Pathol Histotechnol Lab, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Lab Anim Sci Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Lab Cell & Mol Struct, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Dent Ctr, Dept Mol Genet, Boston, MA 02115 USA. RP Ward, JM (reprint author), NCI, Vet & Tumor Pathol Sect, Anim Sci Branch, Off Lab Anim Resources,Div Basic Sci,FCRDC, Fairview 201,POB B, Frederick, MD 21702 USA. EM ward@mail.ncifcrf.gov FU NCI NIH HHS [R01CA67529]; NCRR NIH HHS [RR07036] NR 46 TC 51 Z9 53 U1 0 U2 1 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD MAY PY 1998 VL 35 IS 3 BP 202 EP 208 PG 7 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 167FJ UT WOS:000078621600005 PM 9598583 ER PT J AU Geesaman, BJ Qian, N AF Geesaman, BJ Qian, N TI The effect of complex motion pattern on speed perception SO VISION RESEARCH LA English DT Article DE motion perception; speed illusion; expansion; rotation; translation ID MACAQUE MONKEY; TRANSPARENT MOTION; VISUAL-FIELD; MST NEURONS; IN-DEPTH; MOVEMENT; SENSITIVITY; DIRECTION; STIMULUS; ROTATION AB We recently reported a new motion illusion where dots in expanding random dot patterns appear to move faster than those in rotation patterns despite having the same physical speed distributions. In the current paper, we compared expansion and rotation motion to translational motion and found that the perceived dot speed in translation patterns was between that of expansion and rotation. We also explored contraction motion and found subjects perceived dots in contracting patterns as moving slightly faster than those in expanding patterns and much faster than those in rotating patterns. Finally, we found that stimulus presentation order in a trial plays an important role in determining the magnitude of the speed illusion - the effect is greater when the subjectively faster stimulus is viewed second (e.g., expansion after rotation). The dependence on stimulus order is greatest when comparing complex motion patterns with large subjective speed differences. This phenomenon is unlikely to be explained in terms of channel fatigue or adaptation. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Cambridge, MA 02139 USA. Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. RP Geesaman, BJ (reprint author), Quincy House 517,58 Plympton St, Cambridge, MA 02138 USA. EM geesaman@husc.harvard.edu FU NIMH NIH HHS [MH54125] NR 40 TC 21 Z9 21 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD MAY PY 1998 VL 38 IS 9 BP 1223 EP 1231 DI 10.1016/S0042-6989(97)00279-4 PG 9 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA ZM343 UT WOS:000073529000004 PM 9666990 ER PT J AU Kozlowski, T Ierino, FL Lambrigts, D Foley, A Andrews, D Awwad, M Monroy, R Cosimi, AB Cooper, DKC Sachs, DH AF Kozlowski, T Ierino, FL Lambrigts, D Foley, A Andrews, D Awwad, M Monroy, R Cosimi, AB Cooper, DKC Sachs, DH TI Depletion of anti-Gal alpha 1-3Gal antibody in baboons by specific alpha-Gal immunoaffinity columns SO XENOTRANSPLANTATION LA English DT Article DE natural antibodies; Gal alpha 1,3Gal epitopes; column absorption; apheresis; baboons ID NATURAL ANTIBODIES; IN-VIVO; PIG; IMMUNOADSORPTION; CELLS; PK15 AB Ongoing studies at our center on facilitating transplantation of discordant xenogeneic organs are focused on tolerance induction. To abrogate hyperacute rejection, we have used adsorption methods to eliminate natural anti-Gal alpha 1-3Gal (alpha Gal) antibodies from the circulation of baboons. We have analyzed data concerning antibody removal in baboons that were 1) immunologically naive, 2) receiving conventional pharmacologic immunosuppressive therapy (IS), and 3) treated with a conditioning regimen for tolerance induction. We compared the efficiency of removing alpha Gal antibody 1) by perfusion of whole blood through an alpha Gal affinity column (CP; n=5) with 2) perfusion of plasma (separated from cellular components by apheresis) through an alpha Gal column (CPA; n=39). Our studies demonstrate that 1) CP and CPA are equally effective in removing anti-alpha Gal antibody, 2) CPA is the method of choice if multiple adsorptions are required, 3) CPA in naive animals transiently affects levels of total IgG and ISM, 4) four CPAs repeated at 2-4 day intervals in association with heavy IS reduce the pool of anti-alpha Gal antibody and total Ig, and 5) splenectomy and/or IS delay the return of anti-alpha Gal antibody. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplant Unit, Boston, MA USA. BioTransplant Inc, Charlestown, MA USA. RP Sachs, DH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [1PO1 AI39755] NR 18 TC 94 Z9 94 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 1998 VL 5 IS 2 BP 122 EP 131 DI 10.1111/j.1399-3089.1998.tb00018.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA ZK310 UT WOS:000073306400003 PM 9584826 ER PT J AU Auchincloss, H AF Auchincloss, H TI Literature update 1997, part 3 SO XENOTRANSPLANTATION LA English DT Article C1 Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, GRB 504, Boston, MA 02114 USA. NR 49 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 1998 VL 5 IS 2 BP 164 EP 167 DI 10.1111/j.1399-3089.1998.tb00022.x PG 4 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA ZK310 UT WOS:000073306400007 PM 9584830 ER PT J AU Mentzer, SJ Fingeroth, J Reilly, JJ Perrine, SP Faller, DV AF Mentzer, SJ Fingeroth, J Reilly, JJ Perrine, SP Faller, DV TI Arginine butyrate-induced susceptibility to ganciclovir in an Epstein-Barr virus (EBV)-associated lymphoma SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE immunosuppression; lymphoproliferative disease; post-transplant; lung transplantation; antiviral; thymidine kinase ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDERS; ORGAN TRANSPLANT RECIPIENTS; BONE-MARROW TRANSPLANTATION; ORAL HAIRY LEUKOPLAKIA; GLOBIN GENE-EXPRESSION; MEMBRANE-PROTEIN LMP; LIVER-TRANSPLANTATION; LUNG TRANSPLANTATION; ACYCLOVIR THERAPY; THYMIDINE KINASE AB Lymphoproliferative disorders associated with Epstein-Barr virus (EBV) infections can occur in the setting of immunosuppression. In some patients, the lymphoproliferative disorder can resemble an aggressive monoclonal non-Hodgkins lymphoma (NHL). These NHL are poorly responsive to conventional therapy. Similarly, antiviral therapy with synthetic nucleosides such as ganciclovir are ineffective because the genes that render the virus susceptible to therapy are not expressed in EBV+ lymphomas. Using a cell line derived from a lung transplant recipient with an EBV+ immunoblastic NHL, we studied the ability of arginine butyrate to induce the expression of EBV thymidine kinase. Arginine butyrate was not only effective in inducing EBV thymidine kinase transcription, but also acted synergistically with the antiviral agent ganciclovir to inhibit cell proliferation and decrease cell viability. Based on these findings, the patient from whom the cell line was derived was treated with arginine butyrate/ganciclovir as well as conventional cytotoxic chemotherapy. No additional toxicity was observed with the arginine butyrate/ganciclovir therapy. Histologic examination of the tumor showed substantial necrosis. These observations suggest the feasibility of arginine butyrate induction of ganciclovir susceptibility in patients with EBV-associated lymphomas. (C) 1998 Academic Press. C1 Brigham & Womens Hosp, Div Thorac Surg, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Canc Res, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mentzer, SJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, Dept Surg, 75 Francis St, Boston, MA 02115 USA. FU FDA HHS [FD-R-000831]; NHLBI NIH HHS [HL37118, HL47078] NR 58 TC 64 Z9 66 U1 0 U2 2 PU BLOOD CELLS FOUNDATION PI LA JOLLA PA C/O ERNEST BEUTLER SCRIPPS RES INST, DEPT MOLECULAR EXP MEDICINE, LA JOLLA, CA 92037 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD APR 30 PY 1998 VL 24 IS 8 BP 114 EP 123 DI 10.1006/bcmd.1998.0178 PG 10 WC Hematology SC Hematology GA ZL529 UT WOS:000073442800001 PM 9628848 ER PT J AU Jain, RK AF Jain, RK TI Delivery of molecular and cellular medicine to solid tumors SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 8th International Symposium on Recent Advances in Drug Delivery Systems CY FEB 24-27, 1997 CL SALT LAKE CITY, UT SP Univ Utah, Ctr Controlled Chem Delivery, Alza Corp, Becton Dickinson & Co, Chugai Pharm Co Ltd, Emisphere Technol Inc, Labopharm Inc, MacroMed Inc, Meiji Milk Prod Co Ltd, Pacific Corp, Pharmacia Upjohn Inc, Sam Yang Corp, Shiseido, Theratech Inc, 3M Co, Baxter Healthcare Corp, Boston Sci, Cygnus Therapeut Syst, Focal Inc, Genentech Inc, Hisamitsu Pharm Co Inc, Hoffman La Roche Inc, Novartis, Pfizer Inc, Sankyo Co Ltd, Schering Plough Res Inst, Teikoku Seiyaku Co Ltd, DuPont Merck Pharm Co, VivoRx Inc DE tumor microcirculation; angiogenesis; blood flow; vascular permeability; diffusion and convection; receptor-ligand binding; interstitial pressure; lymphatics; cell adhesion and deformation; cancer detection and treatment ID INTERSTITIAL FLUID PRESSURE; ENDOTHELIAL GROWTH-FACTOR; NATURAL-KILLER-CELLS; VASCULAR-PERMEABILITY FACTOR; COLON ADENOCARCINOMA XENOGRAFT; POSITRON EMISSION TOMOGRAPHY; ENZYME-CONJUGATED ANTIBODIES; INDUCED LEUKOCYTE ADHESION; BLOOD-FLOW; MONOCLONAL-ANTIBODIES AB To reach cancer cells in a tumor, a blood-borne therapeutic molecule or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, and finally migrate through the interstitium. Unfortunately, tumors often develop in ways that hinder each of these steps. Our research goals are to analyze each of these steps experimentally and theoretically, and then integrate the resulting information in a unified theoretical framework. This paradigm of analysis and synthesis has allowed us to obtain a better understanding of physiological barriers in solid tumors, and to develop novel strategies to exploit and/or to overcome these barriers for improved cancer detection and treatment. (C) 1998 Elsevier Science B.V. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 148 TC 131 Z9 134 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 EI 1873-4995 J9 J CONTROL RELEASE JI J. Control. Release PD APR 30 PY 1998 VL 53 IS 1-3 BP 49 EP 67 DI 10.1016/S0168-3659(97)00237-X PG 19 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZM279 UT WOS:000073522600007 PM 9741913 ER PT J AU Puri, KD Chen, SQ Springer, TA AF Puri, KD Chen, SQ Springer, TA TI Modifying the mechanical property and shear threshold of L-selectin adhesion independently of equilibrium properties SO NATURE LA English DT Article ID HYDRODYNAMIC SHEAR; ROLLING ADHESIONS; SIALOMUCIN CD34; P-SELECTIN; LIGAND; FLOW; BOND AB Interactions between adhesion molecules on two different cells differ from interactions between receptors and soluble ligands in that the adhesion molecule interaction (bond) is often subjected to force. It is widely assumed by cell biologists that the 'strength' of a bond is a simple function of the affinity of one adhesion molecule for the other, whereas biophysicists suggest that bonds have 'mechanical properties' that affect their strength. Mechanical properties are a function of the shape of the energy landscape related to bond formation and dissociation, whereas affinity is related only to the net energy change(1-5). Mechanical properties determine the amount by which the kinetics and affinity of bonds are altered by applied force. To date there has been no experimental manipulation of an adhesion molecule that has been shown to affect mechanical properties. L-selectin is an adhesion molecule that mediates lymphocyte binding to, and rolling on, high endothelial venules; these are prerequisites for the emigration of lymphocytes from the bloodstream into lymph nodes. Here we report a selective and reversible chemical modification of a mucin-like ligand that alters the mechanical properties of its bond with L-selectin. The effect of force on the rate of bond dissociation, that is, on a mechanical property, is altered, whereas there is little or no effect of the modification on the rate of bond dissociation in the absence of force. Moreover, the puzzling requirement for hydrodynamic shear flow above a threshold level for L-selectin interactions(6-9) is dramatically altered. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 24 TC 60 Z9 65 U1 0 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 30 PY 1998 VL 392 IS 6679 BP 930 EP 933 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZK759 UT WOS:000073359900051 PM 9582074 ER PT J AU Reilly, JJ Shepard, JO Mark, EJ Rahman, M AF Reilly, JJ Shepard, JO Mark, EJ Rahman, M TI A 49-year-old woman with primary biliary cirrhosis, pulmonary opacities, and a pleural effusion - Lymphocytic interstitial pneumonitis associated with primary biliary cirrhosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LUNG; DISORDERS; VIRUS; INVOLVEMENT; SARCOIDOSIS; ANTIBODIES; FEATURES; DISEASE C1 Brigham & Womens Hosp, Lung Transplant Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Reilly, JJ (reprint author), Brigham & Womens Hosp, Lung Transplant Program, 75 Francis St, Boston, MA 02115 USA. NR 29 TC 2 Z9 2 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 30 PY 1998 VL 338 IS 18 BP 1293 EP 1301 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA ZK547 UT WOS:000073335800009 ER PT J AU Duerr, EM Rollbrocker, B Hayashi, Y Peters, N Meyer-Puttlitz, B Louis, DN Schramm, J Wiestler, OD Parsons, R Eng, C von Deimling, A AF Duerr, EM Rollbrocker, B Hayashi, Y Peters, N Meyer-Puttlitz, B Louis, DN Schramm, J Wiestler, OD Parsons, R Eng, C von Deimling, A TI PTEN mutations in gliomas and glioneuronal tumors SO ONCOGENE LA English DT Article DE PTEN mutations; glioblastoma; oligodendroglioma; ganglioglioma ID LHERMITTE-DUCLOS DISEASE; HUMAN GLIOBLASTOMA-MULTIFORME; MOLECULAR-GENETIC-ANALYSIS; COWDEN SYNDROME; P53 MUTATIONS; CHROMOSOME-10; HETEROZYGOSITY; AMPLIFICATION; ASTROCYTOMA; LOCI AB Cytogenetic and loss of heterozygosity studies have suggested the presence of at least one tumor suppressor gene on chromosome 10 involved in the formation of high grade gliomas, Recently, the PTEN gene, also termed MMAC1 or TEP1, on chromosomal band 10q23 has been identified. Initial studies revealed mutations of PTEN in limited series of glioma cell lines and glioblastomas. In order to systematically evaluate the involvement of PTEN in gliomas, we have analysed the entire PTEN coding sequence by SSCP and direct sequencing in a series of 331 gliomas and glioneuronal tumors. PTEN mutations mere detected in 20/142 glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic astrocytomas and 2/22 oligodendrogliomas, No PTEN mutations were detected in 52 astrocytomas, 37 oligoastrocytomas, three subependymal giant cell astrocytomas, four pleomorphic xanthoastrocytomas, 15 ependymomas, 16 gangliogliomas and one dysembryoplastic neuroepithelial tumor. In addition, all tumors were examined for the presence of homozygous deletions of the PTEN gene; these were detected in 7 glioblastomas that did not have PTEN mutations. Therefore, PTEN mutations occur in approximately 20% of glioblastomas but are rare in lower grade gliomas, These findings confirm that PTEN is one of the chromosome 10 tumor suppressor genes involved in the development of glioblastomas. C1 Univ Bonn, Ctr Med, Dept Neuropathol, D-53105 Bonn, Germany. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Bonn, Med Ctr, Dept Neurosurg, D-53105 Bonn, Germany. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Deimling, A (reprint author), Univ Kliniken Bonn, Inst Neuropathol, Sigmund Freud Str 25, D-53105 Bonn, Germany. RI von Deimling, Andreas/F-7774-2013; OI von Deimling, Andreas/0000-0002-5863-540X; Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [CA57683] NR 37 TC 249 Z9 260 U1 0 U2 8 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 30 PY 1998 VL 16 IS 17 BP 2259 EP 2264 DI 10.1038/sj.onc.1201756 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZK226 UT WOS:000073298000011 PM 9619835 ER PT J AU Hua, QX Jia, WH Bullock, BP Habener, JF Weiss, MA AF Hua, QX Jia, WH Bullock, BP Habener, JF Weiss, MA TI Transcriptional activator-coactivator recognition: Nascent folding of a kinase-inducible transactivation domain predicts its structure on coactivator binding SO BIOCHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; HUMAN PARATHYROID-HORMONE; CAMP RESPONSE ELEMENT; HELIX STOP SIGNAL; FACTOR CREB; CYCLIC-AMP; SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; NMR-SPECTROSCOPY; NUCLEAR-PROTEIN AB A model of transcriptional activator-coactivator recognition is provided by the mammalian CREB activation domain and the KM domain of coactivator CBP. The CREB kinase-inducible activation domain (pKID, 60 residues) is disordered in solution and undergoes an a-helical folding transition on binding to CBP [Radhakrishan, I., Perez-Alvarado, G. C., Parker, D., Dyson, H. J., Montminy, M. R., and Wright, P. E. (1997) Cell 91, 741-752]. Binding requires phosphorylation of a conserved serine (RPpSYR) in pKID associated in vivo with the biological activation of CREB signaling pathways. The CBP-bound structure of CREB contains two alpha-helices (designated alpha A and alpha B) flanking the phosphoserine; the bound structure is stabilized by specific interactions with CBP. Here, the nascent structure of an unbound pKID domain is characterized by multidimensional NMR spectroscopy. The solubility of the phosphopeptide (46 residues) was enhanced by truncation of N- and C-terminal residues not involved in pKID-CBP interactions. Although disordered under physiologic conditions, the pKID fragment and its unphosphorylated parent peptide exhibit partial folding at low temperatures. One recognition helix (alpha A) is well-defined at 4 degrees C, whereas the other (alpha B) is disordered but inducible in 40% trifluoroethanol (TFE). Such nascent structure is independent of serine phosphorylation and correlates with the relative extent of engagement of the two alpha-helices in the pKID-KIX complex; whereas alpha A occupies a peripheral binding site with few intermolecular contacts, the TFE-inducible alpha B motif is deeply engaged in a hydrophobic groove. Our results support the use of TFE as an empirical probe of hidden structural propensities and define a correspondence between induced fit and the nascent structure of peptide fragments. C1 Univ Chicago, Ctr Mol Oncol, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. Univ Chicago, Ctr Mol Oncol, Dept Chem, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Hua, QX (reprint author), Univ Chicago, Ctr Mol Oncol, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. FU NICHD NIH HHS [HD33462]; NIDDK NIH HHS [DK25532] NR 82 TC 69 Z9 70 U1 1 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 APR 28 PY 1998 VL 37 IS 17 BP 5858 EP 5866 DI 10.1021/bi9800808 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL949 UT WOS:000073489700010 PM 9558319 ER PT J AU Oxvig, C Springer, TA AF Oxvig, C Springer, TA TI Experimental support for a beta-propeller domain in integrin alpha-subunits and a calcium binding site on its lower surface SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CRYSTAL-STRUCTURE; GLYCOPROTEIN-IIB; DYNAMIC REGULATION; PLATELET INTEGRIN; MAC-1 CD11B/CD18; LIGAND-BINDING; CELL-ADHESION; EF-HANDS; I-DOMAIN; A-DOMAIN AB Integrins are large, heterodimeric surface molecules of wide importance in cell adhesion. The N-terminal half of all integrin alpha-subunits contains seven weak sequence repeats of approximate to 60 amino acids that are important in ligand binding and have been predicted to fold cooperatively into a single beta-propeller domain with seven beta-sheets. We provide evidence supporting this model with a mouse mAb to human Mac-1 (alpha M beta 2, CD11b/CD18). This antibody, CBRM1/20, binds to amino acid residues that are in different repeats and are 94 residues apart in the primary structure in the loop between strands 1 and 2 of beta-sheet 5 and in the loop between strands 3 and 4 of beta-sheet 6. The 1-2 loops of beta-sheets 5-7 in integrins have EF hand-like Ca2+-binding motifs, CBRM1/20 binds to Mac-1 in the presence of Ca2+ or Sr2+ with an EC50 of 0.2 mM. Mg2+ or Mn2+ cannot substitute. Antibodies to other epitopes on the Mac-1 beta-propeller domain bind in the absence of calcium, mAb CBRM1/20 does not block ligand binding. Thus, the region on the lower surface of the beta-propeller domain to which mAb CBRM1/20 binds does not bind ligand and, furthermore, cannot bind other integrin domains, such as those of the beta-subunit. C1 Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Springer, TA (reprint author), Ctr Blood Res, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA31799, R01 CA031799] NR 45 TC 61 Z9 62 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 APR 28 PY 1998 VL 95 IS 9 BP 4870 EP 4875 DI 10.1073/pnas.95.9.4870 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZL269 UT WOS:000073415700018 PM 9560195 ER PT J AU Hajjar, RJ Schmidt, U Matsui, T Guerrero, JL Lee, KH Gwathmey, JK Dec, GW Semigran, MJ Rosenzweig, A AF Hajjar, RJ Schmidt, U Matsui, T Guerrero, JL Lee, KH Gwathmey, JK Dec, GW Semigran, MJ Rosenzweig, A TI Modulation of ventricular function through gene transfer in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE sarcoplasmic reticulum; phospholamban; calcium; Ca2+ ATPase; adenovirus ID IN-VIVO; MYOCARDIAL-CONTRACTILITY; CALCIUM MOBILIZATION; CARDIAC MYOCYTES; PHOSPHOLAMBAN; ADENOVIRUS; HYPERTROPHY; VECTORS; BINDING; SYSTEM AB We used a catheter-based technique to achieve generalized cardiac gene transfer in vivo and to alter cardiac function by overexpressing phospholamban (PL) which regulates the activity of the sarcoplasmic reticulum Ca2+ ATPase (SERCA2a). By using this approach, rat hearts were transduced in vivo with 5 x 10(9) pfu of recombinant adenoviral vectors carrying cDNA for either PL, beta-galactosidase (beta-gal), or modified green fluorescent protein (EGFP). Western blot analysis of ventricles obtained from rats transduced by Ad.PL showed a 2.8-fold increase in PL compared with hearts transduced by Ad.beta gal, Two days after infection, rat hearts transduced with Ad.PL had lower peak left ventricular pressure (58.3 +/- 12.9 mmHg, n = 8) compared with uninfected hearts (92.5 +/- 3.5 mmHg, n = 6) or hearts infected with Ad.beta gal (92.6 +/- 5.9 mmHg, n = 6), Both peak rate of pressure rise and pressure fall (+3, 210 +/- 298 mmHg/s, -2, 117 +/- 178 mmHg/s, n = 8) were decreased in hearts overexpressing PL compared with uninfected hearts (+5, 225 +/- 136 mmHg/s, -3, 805 +/- 97 mmHg/s, n = 6) or hearts infected with Ad.beta gal (+5, 108 +/- 167 mmHg/s, -3, 765 +/- 121 mmHg/s, n = 6), The time constant of left ventricular relaxation increased significantly in hearts overexpressing PL (33.4 +/- 3.2 ms, n = 8) compared with uninfected hearts (18.5 +/- 1.0 ms, n = 6) or hearts infected with Ad.beta gal (20.8 +/- 2.1 ms, n = 6). These differences in ventricular function were maintained 7 days after infection. These studies open the prospect of using somatic gene transfer to modulate overall cardiac function in vivo for either experimental or therapeutic applications. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Heart Failure & Cardiac Transplantat Ctr, Boston, MA 02129 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St,4th Floor,Room 4207, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL 57623, HL 50361, R01 HL059521, HL 54202] NR 24 TC 198 Z9 203 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 28 PY 1998 VL 95 IS 9 BP 5251 EP 5256 DI 10.1073/pnas.95.9.5251 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZL269 UT WOS:000073415700085 PM 9560262 ER PT J AU Wang, L Martinez, V Barrachina, MD Tache, Y AF Wang, L Martinez, V Barrachina, MD Tache, Y TI Fos expression in the brain induced by peripheral injection of CCK or leptin plus CCK in fasted lean mice SO BRAIN RESEARCH LA English DT Article DE devazepide; central nucleus of the amygdala; paraventricular nucleus of the hypothalamus; nucleus of the solitary tract; arcuate nucleus; fasting ID PARAVENTRICULAR HYPOTHALAMIC NUCLEUS; C-FOS; FOOD-INTAKE; RAT-BRAIN; SYSTEMIC CHOLECYSTOKININ; MESSENGER-RNA; OB/OB MICE; NEURONS; RECEPTOR; AMYGDALA AB We previously reported a synergistic interaction between leptin and cholecystokinin (CCK) to reduce food intake through CCK-A receptors in lean mice fasted for 24 h. To identify the activated neuronal pathways, we investigated changes in Fos expression in brain nuclei 2 h after single or combined intraperitoneal (i.p.) injections of leptin (120 mu g/kg) and sulfated CCK-8 (3.5 mu g/kg) in male lean mice (C57BL/6) fasted for 24 h using immunohistochemistry for Fos, the protein product of the early gene, c-fos. Leptin did not increase Fos expression in the brain compared with vehicle-treated mice. CCK increased the numbers of Fos-positive neurons in the nucleus of the solitary tract (NTS)/area postrema (AP), central nucleus of the amygdala (CeA) and, to a smaller extent, in the paraventricular nucleus of the hypothalamus (PVN) (5.2-, 2.3- and 0.3-fold respectively). Injections of leptin-CCK further enhanced Fos expression by 40% in the PVN compared with that induced by CCK alone, but not in the other nuclei. Devazepide (a CCK-A receptor antagonist, 1 mg/kg, i.p.) prevented the increase in Fos expression induced by leptin-CCK in the PVN and by CCK alone in the PVN, CeA and NTS/AP. These results indicate that in fasted mice, i.p. injection of CCK increases Fos expression in specific brain nuclei through CCK-A receptors while leptin alone had no effect. Leptin in conjunction with CCK selectively enhanced Fos expression in the PVN. The PVN may be an important site mediating the synergistic effect of leptin-CCK to regulate food intake. (C) 1998 Elsevier Science B.V. C1 W Los Angeles VA Med Ctr, CURE Digest Dis Res Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), W Los Angeles VA Med Ctr, CURE Digest Dis Res Ctr, Dept Med, Bldg 115,Rm 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK 30110, DK 41301]; NIMH NIH HHS [MH 00663] NR 62 TC 113 Z9 114 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 27 PY 1998 VL 791 IS 1-2 BP 157 EP 166 DI 10.1016/S0006-8993(98)00091-2 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZP929 UT WOS:000073802600019 PM 9593872 ER PT J AU Khurana, KK Stanley, MW Powers, CN Pitman, MB AF Khurana, KK Stanley, MW Powers, CN Pitman, MB TI Aspiration cytology of malignant neoplasms associated with granulomas and granuloma-like features - Diagnostic dilemmas SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Cytopathology CY NOV 03-09, 1997 CL BOSTON, MASSACHUSETTS SP Amer Soc Cytopathol DE malignant neoplasms; granuloma; epithelioid histiocytic response; epithelioid neoplasms; malignant lymphoma; carcinoma; rheumatoid nodule ID HODGKINS-DISEASE; EPITHELIOID GRANULOMAS; LYMPHOMA; BIOPSY; CYTODIAGNOSIS; SARCOIDOSIS; EFFUSIONS; SARCOMA; CYSTS; CELL AB BACKGROUND. Malignant lymphomas and solid tumors that mimic or are associated with epithelioid granulomas are widely recognized in surgical pathology, but have received little attention in the cytopathology literature. In this study the authors present their experience with six such cases in which the presence of granulomas or granuloma-like features posed a diagnostic difficulty on fine-needle aspiration cytology (FNAC). METHODS. Clinical data, FNAC, and follow-up surgical specimens from six patients presenting with neck masses were reviewed. RESULTS, Only one case was diagnosed confidently as metastatic squamous cell carcinoma with an extensive granulomatous response; the other five were interpreted as "atypical" with descriptive cytology and a differential diagnoses including granulomatous inflammation, in addition to a caveat of "cannot exclude malignancy." Biopsy studies in these cases were recommended in view of the atypical cytologic findings and strong clinical suspicion of malignancy in each case. The histologic findings in two cases revealed Hodgkin's disease with exuberant granulomatous response. The remaining three cases were found to be malignant neoplasms with epithelioid morphologic features and included one example each of diffuse large cell lymphoma, anaplastic carcinoma of the thyroid, and lymphoepithelial carcinoma. CONCLUSIONS, Malignancies associated with granulomas and tumor cells mimicking epithelioid histiocytes may be difficult to diagnose accurately on FNAC. The cytologic differential diagnosis of a "granulomatous" process should include malignant neoplasms. Excisional biopsy studies may be required for definitive diagnosis. (C) 1998 American Cancer Society. C1 SUNY Syracuse, Dept Pathol, Syracuse, NY 13210 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Khurana, KK (reprint author), SUNY Syracuse, Dept Pathol, 750 E Adams St, Syracuse, NY 13210 USA. NR 26 TC 28 Z9 28 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 CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 1998 VL 84 IS 2 BP 84 EP 91 DI 10.1002/(SICI)1097-0142(19980425)84:2<84::AID-CNCR3>3.0.CO;2-D PG 8 WC Oncology; Pathology SC Oncology; Pathology GA ZJ043 UT WOS:000073173800003 PM 9570210 ER PT J AU Moore, A Basilion, JP Chiocca, EA Weissleder, R AF Moore, A Basilion, JP Chiocca, EA Weissleder, R TI Measuring transferrin receptor gene expression by NMR imaging SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE transferrin; transferrin receptor; gene transfer; imaging; NMR; nanoparticle ID ELEMENT-BINDING PROTEIN; IRON; RNA; CELLS AB The human transferrin receptor (hTfR) has been used as a model molecular target to direct therapeutic agents to tumor cells and to shuttle drugs across the blood-brain-barrier. We show in the current study that receptor expression and regulation can be visualized by NMR imaging, when the receptor is probed with a sterically protected iron containing magnetic hTfR probe. We were able to demonstrate that the novel receptor probe was an iron source that could enter the cells via the hTfR but did not play an immediate role in iron downregulation of hTfR within incubation times tested. Using genetically engineered rat 9L gliosarcoma cell lines with three different forms of the hTfR, we also demonstrated that receptor expression and regulation can be visualized by NMR imaging using the probe. This research provides proof of the principle that it is possible to image receptor gene expression and regulation and it demonstrates that it may be possible to image gene transfer in vivo. (C) 1998 Elsevier Science B.V. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Variagen Inc, Cambridge, MA USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Bldg 149,13th St,5403, Charlestown, MA 02129 USA. FU NINDS NIH HHS [1RO1 NS35258-01] NR 15 TC 136 Z9 150 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR 24 PY 1998 VL 1402 IS 3 BP 239 EP 249 DI 10.1016/S0167-4889(98)00002-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZL195 UT WOS:000073408300003 PM 9606982 ER PT J AU Berrueta, L Tirnauer, JS Hill, D Pellman, D Bierer, BE AF Berrueta, L Tirnauer, JS Hill, D Pellman, D Bierer, BE TI Association of EB1 with p150(glued) and cytoplasmic dynein in a 5S protein complex. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Los Andes, Inst Clin Immunol, Merida, Venezuela. Oncogene Sci, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 749 BP A1440 EP A1440 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500902 ER PT J AU Forman-Kay, J Pawson, T Shoelson, S Kay, L AF Forman-Kay, J Pawson, T Shoelson, S Kay, L TI Correlations between structure, dynamics and specific binding in SH2 and PTB domain interactions SO FASEB JOURNAL LA English DT Meeting Abstract C1 Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Prot Engn Network Ctr Excellence, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 92 BP A1324 EP A1324 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500245 ER PT J AU Kaelin, WG Adams, PD Fine, HA Miyake, S Sellers, WR AF Kaelin, WG Adams, PD Fine, HA Miyake, S Sellers, WR TI Control of cell-growth and differentiation by the cyclin/Cdk/RB pathway SO FASEB JOURNAL LA English DT Meeting Abstract C1 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 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 APR 24 PY 1998 VL 12 IS 8 SU S MA 107 BP A1327 EP A1327 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500259 ER PT J AU Lenz, G Luo, Z Avruch, J Rodnight, R Neary, JT AF Lenz, G Luo, Z Avruch, J Rodnight, R Neary, JT TI P2Y purinergic receptor subtypes recruit different MEK activators in astrocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UFRGS, Dept Biofis, Porto Alegre, RS, Brazil. UFRGS, Dept Bioquim, Porto Alegre, RS, Brazil. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. VA Med Ctr, Res Serv, Miami, FL 33215 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL 33215 USA. Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33215 USA. NR 0 TC 2 Z9 2 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 APR 24 PY 1998 VL 12 IS 8 SU S MA 920 BP A1469 EP A1469 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961501076 ER PT J AU Mukerjee, N Okamoto, PM Baksh, S Sagoo, JK Burakoff, SJ Vallee, RB Bierer, BE AF Mukerjee, N Okamoto, PM Baksh, S Sagoo, JK Burakoff, SJ Vallee, RB Bierer, BE TI Identification of a specific calcineurin binding site within dynamin IB. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Fdn Biomed Res, Shrewsbury, MA 01545 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 756 BP A1441 EP A1441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500911 ER PT J AU Norris, TB Silver, PA Flynn, GC AF Norris, TB Silver, PA Flynn, GC TI Characterization of the yeast ER chaperone system SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 634 BP A1420 EP A1420 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500787 ER PT J AU Rao, A Viola, J Aramburu, J Cozar, FG Okamura, H Raghavan, A Hogan, PG AF Rao, A Viola, J Aramburu, J Cozar, FG Okamura, H Raghavan, A Hogan, PG TI Regulation of gene transcription by calcineurin and NFAT. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RI Aramburu, J/G-8991-2014 OI Aramburu, J/0000-0001-9279-9523 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA T15 BP A1298 EP A1298 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500118 ER PT J AU Ruvkun, G Sze, JY Hobert, O AF Ruvkun, G Sze, JY Hobert, O TI Transcriptional control of neural function in C-elegans SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 86 BP A1323 EP A1323 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500239 ER PT J AU Zhang, W Canziani, G Wyatt, R Sodroski, J Sweet, R Kwong, P Hendrickson, W Chaiken, I AF Zhang, W Canziani, G Wyatt, R Sodroski, J Sweet, R Kwong, P Hendrickson, W Chaiken, I TI Probing ligand-induced conformational isomerization in the viral envelope glycoprotein GP120 by optical biosensor kinetic analysis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. SmithKline Beecham, King Of Prussia, PA USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 774 BP A1444 EP A1444 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500929 ER PT J AU Tian, WN Braunstein, LD Pang, JD Stuhlmeier, KM Xi, QC Tian, XN Stanton, RC AF Tian, WN Braunstein, LD Pang, JD Stuhlmeier, KM Xi, QC Tian, XN Stanton, RC TI Importance of glucose-6-phosphate dehydrogenase activity for cell growth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PENTOSE-PHOSPHATE PATHWAY; SIGNAL-TRANSDUCTION; OXIDATIVE STRESS; RAT HEPATOCYTES; TYROSINE PHOSPHORYLATION; MALIC ENZYME; DEHYDROEPIANDROSTERONE; METABOLISM; INHIBITION; MECHANISM AB The intracellular redox potential, which is determined by the level of oxidants and reductants, has been shown to play an important role in the regulation of cell growth. The principal intracellular reductant is NADPH, which is mainly produced by the pentose phosphate pathway through the actions of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, and by g-phosphogluconate dehydrogenase. Previous research has suggested that an increase in G6PD activity is important for cell growth. In this article, we suggest that G6PD activity plays a critical role in cell growth by providing NADPH for redox regulation. The results show the following: 1) inhibition of G6PD activity abrogated growth factor stimulation of [H-3]thymidine incorporation in all cell lines tested; 2) overexpression of G6PD stimulated cell growth, as measured by an increase in [H-3]thymidine incorporations as compared with cells transfected with vector alone; 3) inhibition of G6PD caused cells to be more susceptible to the growth inhibitory effects of H2O2; 4) inhibition of G6PD led to a 30-40% decrease in the NADPH/NADP ratio; and 5) inhibition of G6PD inhibited cell anchorage and significantly decreased the growth-related stimulation of tyrosine phosphorylation. C1 Beth Israel Deaconess Med Ctr, Div Renal, Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stanton, RC (reprint author), Beth Israel Deaconess Med Ctr, Div Renal, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK09265-02] NR 49 TC 268 Z9 280 U1 1 U2 24 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 APR 24 PY 1998 VL 273 IS 17 BP 10609 EP 10617 DI 10.1074/jbc.273.17.10609 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ519 UT WOS:000073224200071 PM 9553122 ER PT J AU Jenkins, TD Opitz, OG Okano, J Rustgi, AK AF Jenkins, TD Opitz, OG Okano, J Rustgi, AK TI Transactivation of the human keratin 4 and Epstein-Barr virus ED-L2 promoters by gut-enriched Kruppel-like factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-SUPPRESSOR GENE; BOX-BINDING PROTEIN; TRANSCRIPTION FACTOR; FACTOR EKLF; EXPRESSION; CELLS; FAMILY; IDENTIFICATION; CARCINOMAS; EPITHELIA AB The Kruppel-like family of transcription factors comprises genes that appear to have tissue-restricted functions, Expression of gut-enriched Kruppel-like factor (GKLF) may be important in the switch from proliferation to differentiation in the squamous epithelium, We sought to determine transcriptionally mediated effects of GKLF on two promoters active in the esophageal squamous epithelium, namely the Epstein-Barr virus ED-LS and human keratin 4 promoters. Both promoters contain a CACCC-like motif previously shown to bind GKLF. To determine whether GI(LF regulates genes containing this element, we first demonstrated expression and then cloned the full-length human GI(LF hom an esophageal squamous carcinoma cell line. In a transient transfection system, GKLF increased the activity of both promoters >25-fold, localized to regions containing the CACCC-like element, Recombinant GKLF specifically binds the CACCC-like motif in both promoters. GKLF epitope-tagged protein leads to the formation of two proteins of 65 and 34 kDa. The chromatographically purified 65-kDa protein binds the CACCC-like element from both Epstein-Barr virus ED-L2 and keratin 4 promoters, which is not attenuated by the 34-kDa protein. In summary, GKLF is expressed in esophageal squamous epithelial cells and transcriptionally activates two esophageal epithelial promoters important at the transition toward differentiation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA 02114 USA. RP Rustgi, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Jackson 904,50 Blossom St, Boston, MA 02114 USA. FU NIDCR NIH HHS [1P01-DE12467-01A1]; NIDDK NIH HHS [DK07191, R01-DK53377] NR 36 TC 75 Z9 78 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 APR 24 PY 1998 VL 273 IS 17 BP 10747 EP 10754 DI 10.1074/jbc.273.17.10747 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZJ519 UT WOS:000073224200089 PM 9553140 ER PT J AU Kelley, CM Ikeda, T Koipally, J Avitahl, N Wu, L Georgopoulos, K Morgan, BA AF Kelley, CM Ikeda, T Koipally, J Avitahl, N Wu, L Georgopoulos, K Morgan, BA TI Helios, a novel dimerization partner of Ikaros expressed in the earliest hematopoietic progenitors SO CURRENT BIOLOGY LA English DT Article ID T-CELL DEVELOPMENT; TRANSCRIPTIONAL CONTROL; STEM-CELLS; C-KIT; GENE; MOUSE; DIFFERENTIATION; LYMPHOCYTES; LYF-1; MICE AB Background: Normal hematopoietic development depends on the activity of the Ikaros transcription factor, which contains distinct zinc-finger domains that mediate DNA binding and protein dimerization. Mice homozygous for a transgene encoding a dominant-negative version of Ikaros that lacks the DNA-binding domain but not the dimerization domain have a more severe phenotype than Ikaros null mice. This observation suggests the presence of factor(s) that can dimerize with Ikaros and partially complement its function. One previously identified factor, Aiolos, probably serves this role in the lymphoid system; a related factor involved in hematopoietic progenitors remains unknown, however. Results: Here, we describe the cloning of an Ikaros-related gene, Hellos. Analysis of the primary sequences of Hellos, Ikaros and Aiolos revealed that the DNA-binding, transcriptional activation and dimerization domains are functionally conserved. Hellos activated transcription from Ikaros DNA-binding sites and could dimerize with itself, Ikaros or Aiolos. Expression of Helios was detected in the earliest hematopoietic sites of the embryo, in hematopoietic stem cells in the adult and was subsequently restricted to a subset of cells in the T cell lineage. Hellos co-localized with Ikaros and Aiolos proteins in macromolecular nuclear structures and formed stable complexes in vivo with the dominant-negative version of Ikaros. Conclusions: Distinct but overlapping expression patterns of members of the Ikaros gene family during hematopoiesis might result in the formation of different multimeric complexes that have specific roles in lineage progression. The preferential expression of Hellos in the earliest stages of hematopoiesis suggests that this gene functions predominantly in early progenitors. (C) Current Biology Ltd ISSN 0960-9822. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dev Biol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Lab Mol Immunol, Charlestown, MA 02129 USA. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dev Biol Lab, Charlestown, MA 02129 USA. EM bmorgan@cbrc.mgh.harvard.edu RI Kelley, Clair/O-2688-2015 FU NIAID NIH HHS [AI33062-06] NR 33 TC 151 Z9 151 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 23 PY 1998 VL 8 IS 9 BP 508 EP 515 DI 10.1016/S0960-9822(98)70202-7 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZK617 UT WOS:000073343100018 PM 9560339 ER PT J AU Maheswaran, S Englert, C Lee, SB Ezzel, RM Settleman, J Haber, DA AF Maheswaran, S Englert, C Lee, SB Ezzel, RM Settleman, J Haber, DA TI E1B 55K sequesters WT1 along with p53 within a cytoplasmic body in adenovirus-transformed kidney cells SO ONCOGENE LA English DT Article DE Wilms tumor; WT1; adenovirus; E1B 55K; sequestation; nuclear body ID WILMS-TUMOR GENE; TRANSCRIPTIONAL REPRESSION; T-ANTIGEN; PROTEIN; APOPTOSIS; LOCALIZATION; ASSOCIATION; COMPLEX; DOMAIN; INHIBITION AB WT1 encodes a tumor suppressor that is expressed in cells of the developing kidney and is inactivated in Wilms tumor, a pediatric kidney cancer. The adenovirus E1B 55K gene product contributes to the transformation of primary baby rat kidney (BRK) cells by binding and inactivating the product of the p53 tumor suppressor. We have previously demonstrated that WT1 and p53 are present within a protein complex in vivo. We non show that WT1 is physically associated with E1B 55K in adenovirus-transformed cells, an interaction that is mediated by the first two zinc fingers of WT1. Immunodepletion of p53 abrogates the coimmunoprecipitation of E1B 55K and WT1, consistent with the presence of a trimeric protein complex containing these three proteins. In the presence of E1B 55K, WT1 which is normally localized in the nucleus, is retained within a very high molecular weight complex and sequestered in the characteristic perinuclear cytoplasmic body that contains E1B 55K and p53, Expression of E1B 55K in osteosarcoma cells that undergo apoptosis following expression of WT1 inhibits WT1-mediated cell death. We conclude that E1B 55K may target WT1 along with p53, resulting in the functional inactivation of both tumor suppressor gene products by this viral oncoprotein. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Surg Res Unit, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA58596] NR 34 TC 35 Z9 35 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 23 PY 1998 VL 16 IS 16 BP 2041 EP 2050 DI 10.1038/sj.onc.1201741 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZJ077 UT WOS:000073177200002 PM 9572485 ER PT J AU Zupke, CA Stefanovich, P Berthiaume, F Yarmush, ML AF Zupke, CA Stefanovich, P Berthiaume, F Yarmush, ML TI Metabolic effects of stress mediators on cultured hepatocytes SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE stress mediators; hepatocyte sandwich culture; factorial design; hepatocyte redox ID TUMOR-NECROSIS-FACTOR; PERFUSED RAT-LIVER; ORGAN FAILURE; INJURY; HUMANS; ACTIVATION; GLUCAGON; INTERLEUKIN-1-BETA; GLUCONEOGENESIS; KETOGENESIS AB Stress mediators play a major role in inducing the hypermetabolic stress state in the liver after major injuries. The majority of studies on the effect of mediators on hepatocytes have focused on single factor effects or on the effect of very complex additives (e.g., serum), and there are no reports which have rigorously identified specific interactions between stress mediators, We used a factorial design experimental approach to evaluate the effects of a four to five day exposure to hormone (glucagon, hydrocortisone, and epinephrine) and cytokine [tumor necrosis factor-alpha (TNF-alpha) interteukin-1 beta (IL-1 beta) and interleukin-6 (IL-6)] stress mediators on stable cultures of rat hepatocytes. Both individual-factor effects and two factor interactions on the metabolism elf urea, glucose, lactate, ketone bodies, albumin, and fibrinogen were evaluated. The cultured hepatocyte model exhibited physiologic responses to the applied stress mediators. While hydrocortisone and epinephrine had no effect, glucagon induced an increase in glucose and urea synthesis. Interleukin-6 increased fibrinogen and decreased albumin production. Furthermore, IL-6 and glucagon caused an increase in the ketone-body ratio (KBR = [acetoacetate]/[beta-hydroxybutyrate]), which is in equilibrium with the intramitochondrial NAD(+)/NADH. Turner necrosis factor-alpha and IL-1 beta, on the other hand, decreased the KBR. An important two-factor interaction between IL-1 beta and IL-6 was identified, namely that it-lp effectively negates the positive effect of IL-6 on the KBR when both are present. These results provide further understanding of the effect of stress mediators on hepatic function and metabolism. These effects may have important implications in the pathogenesis of progressive organ dysfunction which often follows prolonged inflammatory states triggered by major injuries. (C) 1998 John Wiley & Sons, Inc. C1 Massachusetts Gen Hosp, Shriners Burns Inst, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Massachusetts Gen Hosp, Shriners Burns Inst, Ctr Engn Med, Boston, MA 02114 USA. FU NIGMS NIH HHS [5P50 GM-21700-21] NR 34 TC 19 Z9 19 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD APR 20 PY 1998 VL 58 IS 2-3 BP 222 EP 230 DI 10.1002/(SICI)1097-0290(19980420)58:2/3<222::AID-BIT15>3.0.CO;2-E PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA YY542 UT WOS:000072158500015 PM 10191393 ER PT J AU Wang, CY Naka, Y Liao, H Oz, MC Springer, TA Gutierrez-Ramos, JC Pinsky, DJ AF Wang, CY Naka, Y Liao, H Oz, MC Springer, TA Gutierrez-Ramos, JC Pinsky, DJ TI Cardiac graft intercellular adhesion molecule-1 (ICAM-1) and interleukin-1 expression mediate primary isograft failure and induction of ICAM-1 in organs remote from the site of transplantation SO CIRCULATION RESEARCH LA English DT Article; Proceedings Paper CT 69th Annual Scientific Session of the American-Heart-Association CY NOV 09-16, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Heart Assoc, Hoechst Marion Roussel Inc, Kansas City DE cardiac transplantation; leukocyte adhesion receptor; interleukin-1 receptor antagonist; autoinduction ID NECROSIS-FACTOR-ALPHA; RECEPTOR ANTAGONIST BINDS; MONOCLONAL-ANTIBODIES; NEUTROPHIL ADHESION; REPERFUSION INJURY; ALLOGRAFT SURVIVAL; DIASTOLIC FUNCTION; IL-1 RECEPTOR; SEPTIC SHOCK; NITRIC-OXIDE AB During the first few hours after heart transplantation, the occurrence of graft failure is unpredictable and devastating. An explosive cascade of inflammatory vents within the reperfused graft vasculature is likely to be mediated, at least in part, by the local expression of the leukocyte adhesion receptor intercellular adhesion molecule-1 (ICAM-1, CD54). Furthermore, although proinflammatory cytokines such as interleukin-1 (IL-1) are known to autoinduce their own (and ICAM-1) expression in vitro, there are no data to identify their functional in vivo cross talk in the setting of isograft transplantation. To determine the role of ICAM-1 in primary graft failure, we used an isogeneic vascularized model of heterotopic cardiac transplantation, ICAM-1 mRNA and protein increased in grafts during the early posttransplant period and were predominantly localized in the endothelium. The functional significance of this was established using donor hearts obtained from either ICAM-1-deficient (ICAM-1 -/-) or control (ICAM-1 +/+) mice. ICAM-1 +/+ grafts exhibited increased neutrophil infiltration, reduced left ventricular compliance, and poorer survival than did ICAM-1 -/- grafts, increased ICAM-1 expression was not limited to ICAM-1 +/+ grafts but also occurred in unmanipulated recipient organs located remote from the site of surgery (but only after transplantation of ICAM-1 +/+, not ICAM-1 -/-, cardiac grafts). This expression of ICAM-1 in remote organs appeared to be triggered by IL-1 alpha released from the graft, because (1) in situ hybridization revealed increased IL-l mRNA within cells of the reperfused graft, including myocytes and endothelial cells; (2) ICAM-1 expression in remote organs coincided with a significant increase in serum levels of IL-1 alpha after transplantation of ICAM-1 +/+ grafts; both remote organ ICAM-1 expression and IL-1 alpha levels were blunted by implantation of ICAM-1 -/- grafts: and (3) remote organ ICAM-1 expression and neutrophil infiltration and IL-1 levels could be blocked by the administration of an IL-1 receptor antagonist. These data demonstrate an apparent positive-feedback loop in which local ICAM-1 and IL-1 expression leads to a mutual amplification of each other's expression within the reperfused graft, promulgating inflammatory events that are likely to be an important cause of primary cardiac graft failure. Because IL-1 receptor blockade reduces the IL-1-mediated autoinduction of IL-1, reduces the expression of ICAM-1 in both the graft and remote organs, and improves graft survival, it may provide a new and effective strategy to prevent the occurrence of primary cardiac graft failure. C1 Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Pinsky, DJ (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, PH 10 Stem,Room 407,630 W 168th St, New York, NY 10032 USA. EM djp5@columbia.edu FU NHLBI NIH HHS [HL-55397] NR 53 TC 41 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR 20 PY 1998 VL 82 IS 7 BP 762 EP 772 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA ZK048 UT WOS:000073279700003 PM 9562435 ER PT J AU Simpson, SJ Shah, S Comiskey, M de Jong, YP Wang, BP Mizoguchi, E Bhan, AK Terhorst, C AF Simpson, SJ Shah, S Comiskey, M de Jong, YP Wang, BP Mizoguchi, E Bhan, AK Terhorst, C TI T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12 signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; GROWTH-FACTOR-BETA; IFN-GAMMA; TYROSINE PHOSPHORYLATION; INTESTINAL INFLAMMATION; CYTOKINE PRODUCTION; ULCERATIVE-COLITIS; CROHNS-DISEASE; NATURAL-KILLER; SCID MICE AB The requirements for interleukin (IL)-12/signal transducer and activator of transcription (Stat)-4 signaling and induction of T cell-specific interferon (IFN)-gamma expression in the development of T helper cell (Th)1-type pathology were examined in two different models of experimental colitis. In each model, abnormal reconstitution of the T cell compartment in immunodeficient mice by adoptive cell transfer leads to a wasting syndrome and inflammation of the colon, induced by IFN-gamma and tumor necrosis factor (TNF)-alpha-producing T cells. We show here that treatment with anti-IL-12. antibodies in one of the models, or reconstitution with T cells from Stat-4-deficient (Stat-4(null)) mice in both models resulted in a milder disease in the majority of recipient animals, compared with those that were left untreated or that had bet-II reconstituted with wt cells. Protected mice in each group also harbored lower frequencies of IFN-gamma-producing T cells than did diseased mice, suggesting that effects on wasting and colitis resulted from the attenuation of IFN-gamma expression by T cells. To test whether the development of pathogenic T cells in the two colitis models was directly dependent on T cell-specific IFN-gamma expression, IFN-gamma(null) donors were used for T cell reconstitution in each system. Surprisingly, large numbers of IFN-gamma(null)-reconstituted mice developed wasting and colitis, which in many cases was of comparable severity to that seen in animals reconstituted with wt cells. Furthermore, T cells from these animals expressed TNF-alpha, demonstrating that they had retained the ability to produce another proinflammatory cytokine. Taken together, these results demonstrate that in some forms of chronic experimental colitis the development of pathogenic T cells is influenced predominantly, though not exclusively, by IL-12 via the actions of Stat-4 proteins. Furthermore, our data suggest that in the models of colitis studied here the effects of IL-12/Stat-4 or other Th1 promoting pathways are not limited to the induction of IFN-gamma gene expression in T lymphocytes. C1 Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Terhorst, C (reprint author), Harvard Univ, Beth Israel Hosp, Sch Med, Div Immunol, 330 Brookline Ave, Boston, MA 02115 USA. FU NIDDK NIH HHS [R01 DK047677, P30 DK-43551, R01 DK-47677] NR 53 TC 216 Z9 218 U1 0 U2 1 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 APR 20 PY 1998 VL 187 IS 8 BP 1225 EP 1234 DI 10.1084/jem.187.8.1225 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZK126 UT WOS:000073287900007 PM 9547334 ER PT J AU Hata, D Kawakami, Y Inagaki, N Lantz, CS Kitamura, T Khan, WN Maeda-Yamamoto, M Miura, T Han, W Hartman, SE Yao, L Nagai, H Goldfeld, AE Alt, FW Galli, SJ Witte, ON Kawakami, T AF Hata, D Kawakami, Y Inagaki, N Lantz, CS Kitamura, T Khan, WN Maeda-Yamamoto, M Miura, T Han, W Hartman, SE Yao, L Nagai, H Goldfeld, AE Alt, FW Galli, SJ Witte, ON Kawakami, T TI Involvement of Bruton's tyrosine kinase in Fc epsilon RI-dependent mast cell degranulation and cytokine production SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; NECROSIS-FACTOR-ALPHA; AFFINITY IGE RECEPTOR; PLECKSTRIN HOMOLOGY DOMAINS; SIGNAL-TRANSDUCTION PATHWAY; BASOPHILIC LEUKEMIA-CELLS; ACTIVATED T-CELLS; B-CELLS; CROSS-LINKING; DEFICIENT MICE AB We investigated the role of Bruton's tyrosine kinase (Btk) in Fc epsilon RI-dependent activation of mouse mast cells, using xid and btk null mutant mice. Unlike B cell development, mast cell development is apparently normal in these btk mutant mice. However, mast cells derived from these nice exhibited significant abnormalities in Fc epsilon RI-dependent function, xid mice primed with anti-dinitrophenyl monoclonal ISE antibody exhibited mildly diminished early-phase and severely blunted late-phase anaphylactic reactions in response to antigen challenge in vivo. Consistent with this finding, cultured mast: cells derived from the bone marrow cells of rid or btk null mice exhibited mild impairments ill degranulation, and more profound defects in the production of several cytokines, upon Fc epsilon RI cross-linking. Moreover, the transcriptional activities of these cytokine genes were severely reduced in Fc epsilon RI-stimulated btk mutant mast cells. The specificity of these effects of btk mutations was confirmed by the improvement in the ability of btk mutant mast cells to degranulate and to secrete cytokines after the retroviral transfer of wild-type btk cDNA, but rot of vector or kinase-dead btk cDNA. Retroviral transfer of Emt (= Itk/Tsk), Btk's closest relative, also partially improved the ability of btk mutant mast cells to secrete mediators. Taken together, these results demonstrate an important role for Btk in the full expression of Fc epsilon RI signal transduction inn mast cells. C1 La Jolla Inst Allergy & Immunol, Div Allergy, San Diego, CA 92121 USA. Gifu Pharmaceut Univ, Dept Pharmacol, Gifu 502, Japan. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Hematopoiet Factors, Minato Ku, Tokyo 108, Japan. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Howard Hughes Med Inst, Los Angeles, CA 90024 USA. RP Kawakami, T (reprint author), La Jolla Inst Allergy & Immunol, Div Allergy, 10355 Sci Ctr Dr, San Diego, CA 92121 USA. EM toshi_kawakami@liai.org RI Kawakami, Toshiaki/O-1616-2015 FU NCI NIH HHS [R01 CA072074]; NIAID NIH HHS [R01 AI-33617, R01 AI-38348, R01 AI038348, R37 AI-23990, R37 AI023990] NR 90 TC 166 Z9 168 U1 0 U2 1 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 APR 20 PY 1998 VL 187 IS 8 BP 1235 EP 1247 DI 10.1084/jem.187.8.1235 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZK126 UT WOS:000073287900008 PM 9547335 ER PT J AU Yang, YG deGoma, E Ohdan, H Bracy, JL Xu, YX Iacomini, J Thall, AD Sykes, M AF Yang, YG deGoma, E Ohdan, H Bracy, JL Xu, YX Iacomini, J Thall, AD Sykes, M TI Tolerization of anti-Gal alpha 1-3Gal natural antibody-forming B cells by induction of mixed chimerism SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; BONE-MARROW CHIMERAS; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; LYMPHOCYTES-B; ADULT MICE; TOLERANCE; EPITOPES; XENOTRANSPLANTATION; TRANSPLANTATION AB Xenotransplantation could overcome the severe shortage of allogeneic organs, a major factor limiting organ transplantation. Unfortunately, transplantation of organs from pigs, the most suitable potential donor species, results in hyperacute rejection in primate recipients, due to the presence of anti-Gal alpha 1-3Gal (Gal) natural antibodies (NAbs) in their sera. We evaluated the ability to tolerize anti-Gal NAb-producing B cells in alpha 1,3-galactosyltransferase knockout (GalT KO) mice using bone marrow transplantation (BMT) from GalT(+/+) wild-type (WT) mice. Lasting mixed chimerism was achieved in KO mice by cotransplantation of GalT KO and WT marrow after lethal irradiation. The levels of anti-Gal NAb in sera of mixed chimeras were reduced markedly 2 wk after BMT, and became undetectable at later time points. Immunization with Gal(+/+) xenogeneic cells filed to stimulate anti-Gal antibody production in mixed chimeras, whereas the production of non-Gal-specific antixenoantigen antibodies was stimulated. An absence of anti-Gal-producing B cells was demonstrated by enzyme-linked immunospot assays in mixed KO+WT-->KO chimeras. Thus, mixed chimerism efficiently induces anti-Gal-specific a cell tolerance in addition to T cell tolerance, providing a single approach to overcoming both the humoral and the cellular immune barriers to discordant xenotransplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Surg Serv, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA 02129 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01 HL-49915, R01 HL049915] NR 40 TC 127 Z9 128 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 APR 20 PY 1998 VL 187 IS 8 BP 1335 EP 1342 DI 10.1084/jem.187.8.1335 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZK126 UT WOS:000073287900017 PM 9547344 ER PT J AU Borsook, D Becerra, L Fishman, S Edwards, A Jennings, CL Stojanovic, M Papinicolas, L Ramachandran, VS Gonzalez, RG Breiter, H AF Borsook, D Becerra, L Fishman, S Edwards, A Jennings, CL Stojanovic, M Papinicolas, L Ramachandran, VS Gonzalez, RG Breiter, H TI Acute plasticity in the human somatosensory cortex following amputation SO NEUROREPORT LA English DT Article DE amputation; cortical plasticity; pain; phantom; somatotopic ID MASSIVE CORTICAL REORGANIZATION; ADULT MACAQUES; PHANTOM-LIMB; DEAFFERENTATION; HAND; STIMULATION; IMMEDIATE; MONKEYS AB WE Studied a patient after amputation of an arm and found that in less than 24 h stimuli applied on the ipsilateral face were referred in a precise, topographically organized, modality-specific manner to distinct points on the phantom. Functional magnetic resonance imaging (fMRI) performed one month later showed that brush-evoked activity in the brain demonstrates objective signal changes which correlate with perceptual changes in the phantom hand. This finding in humans corresponds to the observations of immediate plasticity in cortical pathways described in animals, including primates. The results suggest that reorganization of sensory pathways occurs very soon after amputation in humans, potentially due to the unmasking of ordinarily silent inputs rather than sprouting of new axon terminals. (C) 1998 Rapid Science Ltd. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH NMR Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthoped Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neural Plast Res Grp, Boston, MA 02114 USA. Univ Calif San Diego, Dept Psychol, La Jolla, CA 92093 USA. RP Borsook, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr, Boston, MA 02114 USA. NR 26 TC 141 Z9 144 U1 4 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 20 PY 1998 VL 9 IS 6 BP 1013 EP 1017 DI 10.1097/00001756-199804200-00011 PG 5 WC Neurosciences SC Neurosciences & Neurology GA ZM026 UT WOS:000073497300012 PM 9601659 ER PT J AU Youmell, M Park, SJ Basu, S Price, BD AF Youmell, M Park, SJ Basu, S Price, BD TI Regulation of the p53 protein by protein kinase C alpha and protein kinase C zeta SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DNA-BINDING FUNCTION; IN-VITRO; ACTIVATION AB The C-terminal of p53 (amino-acids 368-383) represses the DNA binding activity of p53. In vitro, phosphorylation of this region by Protein Kinase C (PKC) is associated with increased DNA binding activity. However, whether PKC can directly modulate p53 function in vivo is not known. Here, we demonstrate that cotransfection of p53 with either PKC alpha or PKC zeta increases p53's transcriptional activity. Mutagenesis of p53 indicates that serine 371 is the major site for phosphorylation by PKC alpha in vitro. Mutation of serine 371 caused a small decline in p53 activation by PKC alpha and PKC zeta. However, the alternatively spliced murine p53, which lacks the PKC phosphorylation sites, still demonstrated increased transcriptional activation when cotransfected with either PKC alpha or PKC zeta. The results indicate that phosphorylation of p53 by PKC in vitro does not correlate with the ability of PKC to upregulate p53's transcriptional activity in vivo. (C) 1998 Academic Press. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy, JF209,44 Binney St, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu FU NCI NIH HHS [CA64585] NR 20 TC 30 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 17 PY 1998 VL 245 IS 2 BP 514 EP 518 DI 10.1006/bbrc.1998.8471 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZK046 UT WOS:000073279500044 PM 9571186 ER PT J AU Koepp, DM Silver, PA AF Koepp, DM Silver, PA TI Nucleocytoplasmic transport and cell proliferation SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE nuclear transport; importin; cell cycle; viral nuclear transport; Ran; Rev; Vpr ID NUCLEAR-PROTEIN IMPORT; SEGREGATION GENE CSE1; BINDING-PROTEIN; EXPORT SIGNAL; HUMAN HOMOLOG; CHROMOSOME CONDENSATION; ACTIVATING PROTEIN; KARYOPHERIN-ALPHA; PORE COMPLEXES; LEPTOMYCIN-B C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 44 Binney St, Boston, MA 02115 USA. NR 84 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD APR 17 PY 1998 VL 1377 IS 2 BP M39 EP M47 DI 10.1016/S0304-419X(97)00036-X PG 9 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA ZL946 UT WOS:000073489400001 PM 9606975 ER PT J AU Spiegelman, BM AF Spiegelman, BM TI PPAR gamma in monocytes: Less pain, any gain? SO CELL LA English DT Review ID ADIPOGENESIS; LIGAND; J(2) C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. NR 16 TC 122 Z9 126 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 17 PY 1998 VL 93 IS 2 BP 153 EP 155 DI 10.1016/S0092-8674(00)81567-6 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ045 UT WOS:000073174000002 PM 9568708 ER PT J AU Isenberg, G Goldmann, WH AF Isenberg, G Goldmann, WH TI Peptide-specific antibodies localize the major lipid binding sites of talin dimers to oppositely arranged N-terminal 47 kDa subdomains SO FEBS LETTERS LA English DT Article DE electron microscopy; lipid binding site; peptide-specific antibody; talin ID CYTOSKELETAL PROTEIN TALIN; ACTIN-BINDING; ADHESION PLAQUES; CELL-ADHESION; VINCULIN; FIBROBLASTS; MEMBRANES; CONTAINS; DOMAINS AB Using ultrastructural analysis and labeling with polyclonal antibodies that recognize peptide sequences specific for phospholipid binding, we mapped the functional domain structure of intact platelet talin and its proteolytic fragments. The talin dimer, which is crucial for actin and lipid binding, is built of a backbone containing the 200 kDa rod portions, at both ends of which a 47 kDa globular domain is attached. Peptide-specific polyclonal antibodies were raised against three potential lipid binding sequences residing within the N-terminal 47 kDa domain (i.e. S19, amino acids 21-39; H18, amino acids 287-304; and H17, amino acids 385-406), Antibodies H17 and H18 localize these lipid binding sequences within the N-terminal 47 kDa globular talin subdomains opposed at the outer 200 kDa rod domains within talin dimers, Hence, we conclude that in its dimeric form, which is used in actin and lipid binding, talin is a dumbbell-shaped molecule built of two antiparallel subunits. (C) 1998 Federation of European Biochemical Societies. C1 Tech Univ Munich, Biophys Dept E22, D-85747 Garching, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Charlestown, MA 02129 USA. RP Isenberg, G (reprint author), Tech Univ Munich, Biophys Dept E22, James Franck Str, D-85747 Garching, Germany. RI Goldmann, Wolfgang/H-5572-2013 NR 38 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 17 PY 1998 VL 426 IS 2 BP 165 EP 170 DI 10.1016/S0014-5793(98)00336-6 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZK237 UT WOS:000073299100002 PM 9599000 ER PT J AU Goldmann, WH Guttenberg, Z AF Goldmann, WH Guttenberg, Z TI Examination of temperature-induced 'gel-sol' transformation of alpha-actinin/cross-linked actin networks by static light scattering SO FEBS LETTERS LA English DT Article DE actin; alpha-actinin; binding kinetics; light scattering ID F-ACTIN; MECHANICAL-PROPERTIES; CHICKEN GIZZARD; BINDING; PROTEIN; QUANTITATION; CYTOSKELETON; COMPLEX AB We studied the gel-sol transformation of F-actin/alpha-actinin solutions. Gross-linking of actin filaments by a-actinin shows a temperature-dependent increase in light scatter signal, (I)T. Higher F-actin/alpha-actinin molar ratios, r(A alpha) as well as increases in F-actin concentration, [A], and reduction of actin filament lengths, r(AG), augment the maximal light intensity, I and shift the gel-sol transition point, T-g to higher temperatures. This behavior is interpreted in terms of the model developed by Tempel, M., Isenberg, G. and Sackmann, E. (1996) (Physical Review E 54, 1802-1810) based on the percolation theory. Using the temperature-dependent binding model of this theory allows instant prediction of the equilibrium constant, K for F-actin/alpha-actinin solutions at temperatures T< T-g. (C) 1998 Federation of European Biochemical Societies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Res Labs, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Res Labs, Bldg 149,13th St, Charlestown, MA 02129 USA. EM goldman@helix.mgh.harvard.edu RI Goldmann, Wolfgang/H-5572-2013 NR 30 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 17 PY 1998 VL 426 IS 2 BP 255 EP 259 DI 10.1016/S0014-5793(98)00353-6 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZK237 UT WOS:000073299100021 PM 9599019 ER PT J AU Rhoads, DB Rosenbaum, DH Unsal, H Isselbacher, KJ Levitsky, LL AF Rhoads, DB Rosenbaum, DH Unsal, H Isselbacher, KJ Levitsky, LL TI Circadian periodicity of intestinal Na+/glucose cotransporter 1 mRNA levels is transcriptionally regulated SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PYRUVATE-KINASE GENE; CRYPT-VILLUS AXIS; FRUCTOSE TRANSPORTER GLUT5; RAT SMALL-INTESTINE; GLUCOSE TRANSPORTERS; MESSENGER-RNA; FUNCTIONAL-CHARACTERIZATION; TISSUE DISTRIBUTION; EXPRESSION; LIVER AB Intestinal expression of the high affinity Na+/glucose cotransporter 1 (SGLT1), which absorbs dietary glucose and galactose, exhibits both circadian periodicity in its activity and induction by dietary carbohydrate. Because the daily variation in SGLT1 activity is established by the feeding schedule (whether ad libitum or imposed) and persists in the absence of food, this variation has been described as anticipatory. To delineate the mechanisms regulating SGLT1, its expression was examined in rats maintained in a 12-h photoperiod with free access to chow. SGLT1 mRNA levels varied significantly, with the maximum abundance occurring near the onset of dark. and the minimum near the onset of light. The SGLT1 transcription rate was 7-fold higher in the morning (1000-1100 h) than in the afternoon (1600-1700 h). An element for hepatocyte nuclear factor 1 (HNF-1) was identified in the SGLT1 promoter that formed different complexes with small intestinal nuclear extracts, depending on the time when the source animal was killed. Serological tests indicated that HNF-1 alpha was present in complexes throughout the day, while HNF-1 beta binding exhibited circadian periodicity. We propose that exchange of HNF-1 dimerization partners contributes to circadian changes in SGLT1 transcription, Because SGLT1 mRNA levels also varied in rhesus monkeys (offset by approximately one-half day from rats), a similar mechanism appears to be present in primates. C1 Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Rhoads, DB (reprint author), Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. FU NICHD NIH HHS [HD31215]; NIDDK NIH HHS [5P30 DK40561, DK01392] NR 48 TC 85 Z9 85 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 APR 17 PY 1998 VL 273 IS 16 BP 9510 EP 9516 DI 10.1074/jbc.273.16.9510 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800025 PM 9545279 ER PT J AU Bodor, J Habener, JF AF Bodor, J Habener, JF TI Role of transcriptional repressor ICER in cyclic AMP-mediated attenuation of cytokine gene expression in human thymocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED T-CELLS; RESPONSE ELEMENT-BINDING; ACCESSORY MOLECULE CD28; INTERLEUKIN-2 PROMOTER; CAMP INHIBITION; PROTEIN-KINASE; NUCLEAR FACTOR; IL-2; CREB; LYMPHOCYTES AB Proliferating human medullary thymocytes can exhibit characteristic T helper cell type 1 cytokine responses exemplified by the immediate early expression of interleukin-2, interferon-gamma, tumor necrosis factor-alpha, and lymphotoxin-beta. Here we report that cAMP-mediated attenuation of the transcription of T helper-1-specific cytokine genes in human medullary thymocytes correlates with the induction of the cAMP-mediated transcriptional repressor ICER (inducible cAMP early repressor). We show that ICER binds specifically to several NFAT/AP-1 (nuclear factor of activated T cells/activating protein-1) composite DNA sites essential for the activation of the interleukin (IL)-2 promoter as well as to a homologous DNA motif present in the proximal segment of the interferon-gamma promoter, In the presence of the minimal NFAT DNA-binding domain, which is sufficient for both DNA binding and AP-1 complex formation, ICER and NFAT form NFAT/ICER ternary complexes on several NFAT/AP-1 DNA composite sites previously identified as essential for the expression of the immunoregulatory cytokines such as IL-2, IL-4, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha. In extracts prepared from human medullary thymocytes treated with forskolin and ionomycin, these composite sites bind endogenously expressed ICER either singly or in complexes. Moreover, in Jurkat cells, ectopically expressed ICER represses transcription from NFAT-mediated, phorbol ester/ionophore-activated IL-2, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor-alpha promoters. We present evidence that ICER interactions with NFAT/AP-1 composite DNA sites correlate with its ability to repress transcription. These findings provide further insight into the mechanisms involved in cAMP-mediated transcriptional attenuation of cytokine expression. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab,Howard Hughes Med Inst, Boston, MA 02114 USA. RP Bodor, J (reprint author), NCI, Expt Immunol Branch, Div Basic Sci, NIH, Bldg 10,R4B14,10 Ctr Dr, Bethesda, MD 20892 USA. EM Bodorj@exchange.nih.gov FU NIDDK NIH HHS [DK 25532] NR 46 TC 94 Z9 97 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 APR 17 PY 1998 VL 273 IS 16 BP 9544 EP 9551 DI 10.1074/jbc.273.16.9544 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800030 PM 9545284 ER PT J AU Jackson, JG White, MF Yee, D AF Jackson, JG White, MF Yee, D TI Insulin receptor substrate-1 is the predominant signaling molecule activated by insulin-like growth factor-I, insulin, and interleukin-4 in estrogen receptor-positive human breast cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; IGF-I; TYROSINE PHOSPHORYLATION; GLUCOSE-TRANSPORT; IRS-1; EXPRESSION; KINASE; PROTEINS; LINE; SHC AB Because insulin-like growth factor-I (IGF-I), insulin, and interleukin-4 (IL-4) have known biological effects in breast cancer cells and signal through insulin receptor substrate (IRS) adaptor proteins, we examined the expression and function of IRS-1 and IRS-2 in breast tumors and cell lines. IRS-1 and IRS-2 were expressed by cell lines and primary breast tumor specimens. IGF-I, insulin, and IL-4 treatment of MCF-7 and ZR-75, and IGF-I treatment of T47-D breast cancer cells, resulted in much greater tyrosine phosphorylation of IRS-1 compared with IRS-2. Furthermore, IGF-I stimulated greater tyrosine phosphorylation of IRS-1 than either insulin or IL-4. IGF-I treatment also enhanced association of the p85 regulatory subunit of phosphatidylinositol S-kinase with IRS-1 and stimulated increased enzymatic activity compared with IL-4 and insulin in all three cell lines. Similarly, mitogen-activated protein kinase activity was greater in IGF-I-stimulated cells. To determine the functional significance of the activation of these pathways, we inhibited activation of phosphatidylinositol 3-kinase with wortmannin and mitogen-activated protein kinase with PD098059. Both compounds inhibited IGF-stimulated growth, suggesting that both pathways contributed to the mitogenic response to IGF-I. We conclude that IRS-1, and not IRS-2, is the predominant signaling molecule activated by IGF-I, insulin, and IL-4. Furthermore, enhanced tyrosine phosphorylation of IRS-1 by IGF-I, compared with either insulin or IL-4, is associated with greater activation of mitogenic downstream signaling pathways resulting in enhanced cell growth. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78284 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Yee, D (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM doug@oncology.uthscsa.edu FU NCI NIH HHS [KO4 CA 01670, P01 CA 30195, P30 CA 54174] NR 50 TC 140 Z9 141 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 APR 17 PY 1998 VL 273 IS 16 BP 9994 EP 10003 DI 10.1074/jbc.273.16.9994 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800091 PM 9545345 ER PT J AU Mahdi, NA Lopez, J Leon, M Pathan, A Harrell, L Jang, IK Palacios, IF AF Mahdi, NA Lopez, J Leon, M Pathan, A Harrell, L Jang, IK Palacios, IF TI Comparison of primary coronary stenting to primary balloon angioplasty with stent bailout for the treatment of patients with acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID IMMEDIATE ANGIOPLASTY; PLASMINOGEN-ACTIVATOR; THREATENED CLOSURE; ARTERY DISEASE; STREPTOKINASE; IMPLANTATION; THROMBOLYSIS; EXPERIENCE; TRIAL AB This study compares the immediate and long-term outcomes of a primary coronary stenting strategy with primary balloon angioplasty with stent bailout in the treatment of patients with acute myocardial infarction (AMI). One hundred forty-seven consecutive patients who underwent primary balloon angioplasty with stent bailout (n = 94) or primary stenting (n = 53) for AMI were clinically followed for 8.1 +/- 5.7 and 8.5 +/- 4.5 months, respectively. Immediate results, as well as in-hospital and long-term ischemic events (death, reinfarction, and repeat revascularization) were compared between both groups. Angiographic success was 91.5% in the balloon angioplasty group and 94% in the stent group. In-hospital and late follow-up combined ischemic events were 22 of 94 (23%) versus 0 of 53 (0%); p <0.001 and 33 of 78 (42%) versus 13 of 53 (25%), p = 0.04 for the balloon angioplasty and stent groups, respectively. At 6 months, the cumulative probability of repeat target lesion revascularization was higher in the balloon angioplasty group (47% vs 18%, p = 0.0006) as was the probability of lan target revascularization (36% vs 18% p = 04046); the cumulative event-free survival after 6 months was significantly lower in the balloon angioplasty group (44% vs 80%, p = 0.0001). This study demonstrates that a primary stent placement strategy in patients with AMI is safe, feasible, and superior to primary balloon angioplasty with stent bailout. Primary stenting results in a larger postprocedural minimal luminal diameter, a lower early and lan recurrent ischemic event rate, and a lower incidence of target lesion revascularization at follow-up. (C) 1998 by Excerpta Medico, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit,Cardiac Catheterizat Lab, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit,Cardiac Catheterizat Lab, Bulfinch 105,Fruit St, Boston, MA 02114 USA. NR 30 TC 24 Z9 25 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 1998 VL 81 IS 8 BP 957 EP 963 DI 10.1016/S0002-9149(98)00072-1 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZK092 UT WOS:000073284100004 PM 9576153 ER PT J AU Freedman, R AF Freedman, R TI Basic and clinical approaches to the genetics of deficits in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Colorado, Dept Psychiat, Denver, CO 80262 USA. Denver VAMC, Denver, CO 80262 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 1 BP 1S EP 1S DI 10.1016/S0006-3223(98)00102-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700003 ER PT J AU Nahas, Z Stallings, LE Speer, AM Teneback, C Vincent, DJ Bohning, DE Spicer, KM Cheng, KT Molloy, M Risch, SC George, MS AF Nahas, Z Stallings, LE Speer, AM Teneback, C Vincent, DJ Bohning, DE Spicer, KM Cheng, KT Molloy, M Risch, SC George, MS TI Perfusion SPECT studies of rTMS effects on blood flow in health and depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 63 BP 19S EP 20S DI 10.1016/S0006-3223(98)90511-X PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700065 ER PT J AU Kanter, ED Peskind, ER Dobie, DJ Wilkinson, CW Raskind, MA AF Kanter, ED Peskind, ER Dobie, DJ Wilkinson, CW Raskind, MA TI Glucocorticoid feedback inhibition of the HPA axis in PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 180 BP 53S EP 53S DI 10.1016/S0006-3223(98)90628-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700182 ER PT J AU Green, MF AF Green, MF TI Moving beyond symptom reduction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles VA Med Ctr, Los Angeles, CA 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 201 BP 59S EP 59S DI 10.1016/S0006-3223(98)90649-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700203 ER PT J AU Fava, M Rosenbaum, J Hoog, S Krebs, W Dillon, J AF Fava, M Rosenbaum, J Hoog, S Krebs, W Dillon, J CA Fluoxetine Collaborat Study Grp TI A comparison of symptoms following treatment interruption: Evidence from a randomized, double-blind trial with fluoxetine, sertraline, and paroxetine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 APR 15 PY 1998 VL 43 SU 8 MA 234 BP 69S EP 69S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700236 ER PT J AU George, MS Nahas, Z Speer, AM Avery, D Molloy, M Risch, SC Lorberbaum, JP Bohning, DE Post, RM AF George, MS Nahas, Z Speer, AM Avery, D Molloy, M Risch, SC Lorberbaum, JP Bohning, DE Post, RM TI How does TMS improve depression? Current hints about the role of intensity, frequency, location and dose SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 253 BP 76S EP 76S DI 10.1016/S0006-3223(98)90701-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700255 ER PT J AU Rauch, SL Whalen, PJ Savage, CR Curran, T Bush, G McInerney, S Jenike, MA AF Rauch, SL Whalen, PJ Savage, CR Curran, T Bush, G McInerney, S Jenike, MA TI New neuroimaging probes for the study of OCD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 256 BP 77S EP 77S DI 10.1016/S0006-3223(98)90704-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700258 ER PT J AU van Kammen, DP Kelley, ME Yao, JK Tsai, G Coyle, JT AF van Kammen, DP Kelley, ME Yao, JK Tsai, G Coyle, JT TI The role of glutamate and HVA in schizophrenic symptomatology SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Vet Adm Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 276 BP 83S EP 83S DI 10.1016/S0006-3223(98)90724-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700278 ER PT J AU Michelson, D Lydiard, RB Pollack, MH Tamura, R Tepner, R AF Michelson, D Lydiard, RB Pollack, MH Tamura, R Tepner, R TI Fluoxetine treatment of panic disorder: A randomized, placebo-controlled, multi-center trial SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Eli Lilly & Co, Indianapolis, IN 46285 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 305 BP 91S EP 92S DI 10.1016/S0006-3223(98)90753-3 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700307 ER PT J AU Michelson, D Lydiard, RB Pollack, M Tamura, R Tepner, R Tollefson, G AF Michelson, D Lydiard, RB Pollack, M Tamura, R Tepner, R Tollefson, G TI Long-term treatment in panic disorder: Randomization of acute fluoxetine responders to continued treatment with fluoxetine or placebo SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Eli Lilly & Co, Indianapolis, IN 46285 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 306 BP 92S EP 92S DI 10.1016/S0006-3223(98)90754-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700308 ER PT J AU Nahas, Z Speer, A Molloy, M Arana, GW Risch, SC George, MS AF Nahas, Z Speer, A Molloy, M Arana, GW Risch, SC George, MS TI Frequency and intensity in the antidepressant effect of left prefrontal rTMS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIMH, Dept Psychiat, Bethesda, MD 20892 USA. NIMH, Dept Radiol, Bethesda, MD 20892 USA. NIMH, Dept Neurol, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. NR 1 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 315 BP 94S EP 95S DI 10.1016/S0006-3223(98)90763-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700317 ER PT J AU Gerner, RH Kaufman, KR Rosen, R AF Gerner, RH Kaufman, KR Rosen, R TI Seizures associated with bupropion and SSRI co-therapy SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Psychiat, New Brunswick, NJ 08901 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08901 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 329 BP 99S EP 99S DI 10.1016/S0006-3223(98)90777-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700331 ER PT J AU Gerner, RH Kaufman, KR Rosen, R AF Gerner, RH Kaufman, KR Rosen, R TI Seizures associated with bupropion and SSRIs & serum levels SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Psychiat, New Brunswick, NJ 08901 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08901 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 336 BP 101S EP 101S DI 10.1016/S0006-3223(98)90784-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700338 ER PT J AU Fava, M Rosenbaum, JF Hoog, S Tepner, R Kopp, J Sayler, M AF Fava, M Rosenbaum, JF Hoog, S Tepner, R Kopp, J Sayler, M CA Fluoxetine Collaborative Study Grp TI Fluoxetine versus sertraline and paroxetine in major depression: Safety and efficacy in patients with low and high baseline insomnia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Indianapolis, IN 46285 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 341 BP 102S EP 103S DI 10.1016/S0006-3223(98)90789-2 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700343 ER PT J AU Fava, M Rosenbaum, JF Hoog, S Tepner, R Kopp, J Sayler, M AF Fava, M Rosenbaum, JF Hoog, S Tepner, R Kopp, J Sayler, M CA Fluoxetine Collaborative Study Grp TI Fluoxetine versus sertraline and paroxetine in major depression: Safety and efficacy in anxious and nonanxious subgroups SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 342 BP 103S EP 103S DI 10.1016/S0006-3223(98)90790-9 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700344 ER PT J AU Frazer, A Gould, G AF Frazer, A Gould, G TI Affinity of alpha(2) adrenoceptors in brain areas for mirtazapine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 353 BP 106S EP 106S DI 10.1016/S0006-3223(98)90801-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700355 ER PT J AU Reddy, RD van Kammen, DP Yao, JK AF Reddy, RD van Kammen, DP Yao, JK TI Cigarette smoking and antioxidant status in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15206 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 374 BP 112S EP 113S DI 10.1016/S0006-3223(98)90822-8 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700376 ER PT J AU Yao, JK Reddy, RD van Kammen, DP McElhinny, LG Korbanic, CW AF Yao, JK Reddy, RD van Kammen, DP McElhinny, LG Korbanic, CW TI Reduced level of the antioxidant proteins in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 410 BP 123S EP 123S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700412 ER PT J AU Yao, JK van Kammen, DP Reddy, RD Kelley, ME AF Yao, JK van Kammen, DP Reddy, RD Kelley, ME TI Superoxide dismutase and negative symptoms in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 412 BP 123S EP 124S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700414 ER PT J AU Yao, JK Reddy, RD van Kammen, DP McElhinny, LG AF Yao, JK Reddy, RD van Kammen, DP McElhinny, LG TI Blood glutathione peroxidase and symptom severity in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 411 BP 123S EP 123S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700413 ER PT J AU Elman, I Gastfriend, DR Adler, CM Malhotra, AK Bir, C Pickar, D Breier, A AF Elman, I Gastfriend, DR Adler, CM Malhotra, AK Bir, C Pickar, D Breier, A TI Effects of acute metabolic stress on pituitary-adrenal axis activation in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1998 VL 43 SU 8 MA 415 BP 124S EP 125S DI 10.1016/S0006-3223(98)90863-0 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZJ674 UT WOS:000073240700417 ER PT J AU Gainsford, T Roberts, AW Kimura, S Metcalf, D Dranoff, G Mulligan, RC Begley, CG Robb, L Alexander, WS AF Gainsford, T Roberts, AW Kimura, S Metcalf, D Dranoff, G Mulligan, RC Begley, CG Robb, L Alexander, WS TI Cytokine production and function in c-mpl-deficient mice: No physiologic role for interleukin-3 in residual megakaryocyte and platelet production SO BLOOD LA English DT Article ID LEUKEMIA INHIBITORY FACTOR; HEMATOPOIETIC STEM-CELLS; IN-VITRO; THROMBOPOIETIN; GROWTH; LIGAND; THROMBOCYTOPENIA; PROGENITORS; STIMULATION; LACKING AB Mice lacking thrombopoietin (TPO), or its receptor c-Mpl, display defective megakaryocyte and platelet development and deficiencies in progenitor cells of multiple hematopoietic lineages. The contribution of alternative cytokines to thrombopoiesis in the absence of TPO signalling was examined in mpl(-/-) mice. Analysis of serum and organ-conditioned media showed no evidence of a compensatory overproduction of megakaryocytopoietic cytokines. However, consistent with a potential role in vivo, when injected into mpl(-/-) mice, interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) retained the capacity to elevate megakaryocytes and their progenitors in hematopoietic tissues and increase circulating platelet numbers, However, double mutant mice bred to carry genetic defects both in c-Mpl and IL-3 or the alpha chain of the IL-3 receptor, displayed no greater deficiencies in megakaryocytes or platelets than mpl-deficient animals, suggesting absence of a physiologic role for IL-3 in the residual megakaryocytopoiesis and platelet production in these mice. (C) 1998 by The American Society of Hematology. C1 Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, PO Royal Melbourne Hosp, Parkville, Vic 3050, Australia. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Alexander, WS (reprint author), Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, PO Royal Melbourne Hosp, Parkville, Vic 3050, Australia. RI Roberts, Andrew/C-6736-2012 OI Roberts, Andrew/0000-0002-7341-5720 FU NCI NIH HHS [CA22556] NR 35 TC 47 Z9 48 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 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1998 VL 91 IS 8 BP 2745 EP 2752 PG 8 WC Hematology SC Hematology GA ZG521 UT WOS:000073012000016 PM 9531584 ER PT J AU Frey, BM Hackett, NR Bergelson, JM Finberg, R Crystal, RG Moore, MAS Rafii, S AF Frey, BM Hackett, NR Bergelson, JM Finberg, R Crystal, RG Moore, MAS Rafii, S TI High-efficiency gene transfer into ex vivo expanded human hematopoietic progenitors and precursor cells by adenovirus vectors SO BLOOD LA English DT Article ID C-KIT-LIGAND; IMMUNOSTIMULATORY DENDRITIC CELLS; COLONY-STIMULATING FACTOR; BONE-MARROW; ADHESION MOLECULES; IN-VITRO; MEGAKARYOCYTIC DIFFERENTIATION; SURFACE EXPRESSION; CD34+ CELLS; HUMAN BLOOD AB Replication-deficient adenoviral vectors (AdVec), which infect cycling and noncycling cells with high efficiency, low toxicity, and ease of delivery, provide ideal vehicles to study the expression of regulatory genes controlling different stages of hematopoiesis. To examine the infection efficiency of AdVec in hematopoietic precursor and progenitor cells, we used a replication-deficient adenovector expressing the humanized form of the cDNA for green fluorescent protein (AdGFP), permitting assessment of infection efficiency and kinetics of transgene expression in viable hematopoietic cells using flow cytometry and fluorescence microscopy. Flow-cytometric analysis of ex vivo expanded hematopoietic precursor cells infected with a multiplicity of infection (MOI) of 100 of AdGFP show that 78% of megakaryocytic (CD41a(+) and CD42b(+)) cells, 82% of dendritic (CD1a(+)) cells, 41% of RBC precursors (glycophorin A(+)), and 32% of monocytic (CD14(+)) cells expressed GFP. Nineteen percent +/- 1% of freshly isolated CD34(+) cells from peripheral blood leukapheresis products infected under the same conditions expressed GFP. Morphologic evaluation of ex vivo expanded, AdGFP-infected CD34(+) cells showed normal maturation, The functional capacity of AdGFP-infected CD34(+) cells was analyzed by quantifying clonogeneic efficiency and proliferative capacity, Infection of CD34(+) progenitor cells with MOls of 1 to 100 did not impair clonogeneic efficiency of CD34(+) cells. However, MOI greater than 100 resulted in a significant inhibition of colony-forming unit-granulocyte/granulocyte-macrophage (CFU-G/GM) formation, In sequential dilution expansion over 3 weeks (Delta assay), the cytokine-driven proliferative potential of CD34(+) cells was not impaired following exposure to AdGFP at MOls of 1 to 1,000, The GFP(+) population expanded 10- to 15-fold at high MOls (500 to 1,000), indicating multiple copies of the transgene in the initially infected CD34(+) cells, which were expressed in subsequent progenies. These data show that AdVec deliver transgenes with high efficiency and low toxicity to hematopoietic progenitor and precursor cells, Introduction of marker genes such as GFP into hematopoietic cells by AdVec will provide a valuable system for study of development, homing, and trafficking of hematopoietic precursor and progenitor cells in vitro and in vivo. Furthermore, these results provide insights into the design of gene therapy strategies for treatment of hematologic disorders by AdVec. (C) 1998 by The American Society of Hematology. C1 Cornell Univ, Coll Med, Div Hematol Oncol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, James Ewing Lab Dev Hematopoiesis, New York, NY 10021 USA. Cornell Univ, Med Ctr, New York Hosp, Div Pulm & Crit Care Med, New York, NY 10021 USA. Harvard Univ, Dana Farber Canc Inst, Infect Dis Lab, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Philadelphia, PA 19104 USA. RP Rafii, S (reprint author), Cornell Univ, Coll Med, Div Hematol Oncol, 1300 York Ave,Room C-616, New York, NY 10021 USA. RI Finberg, Robert/E-3323-2010 FU NHLBI NIH HHS [K08HL 02926, R01-HL-58707-01]; NIDDK NIH HHS [R01-DK-42693] NR 55 TC 74 Z9 75 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 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1998 VL 91 IS 8 BP 2781 EP 2792 PG 12 WC Hematology SC Hematology GA ZG521 UT WOS:000073012000020 PM 9531588 ER PT J AU Samuels, BL Herndon, JE Harmon, DC Carey, R Aisner, J Corson, JM Suzuki, Y Green, MR Vogelzang, NJ AF Samuels, BL Herndon, JE Harmon, DC Carey, R Aisner, J Corson, JM Suzuki, Y Green, MR Vogelzang, NJ TI Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma - A Phase II study by the cancer and leukemia group B SO CANCER LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 14-17, 1994 CL DALLAS, TEXAS SP Amer Soc Clin Oncol DE medical oncology; mesothelioma; cisplatin; dihydro-5-azacytidine; Phase II study ID PLEURAL MESOTHELIOMA; EXTRAPLEURAL PNEUMONECTOMY; CLINICAL-TRIALS; CHEMOTHERAPY; CARBOPLATIN; DOXORUBICIN; MANAGEMENT; DIFFUSE AB BACKGROUND, In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of patients with advanced, previously untreated mesothelioma, dihydro-5-azacytidine (DHAC) demonstrated a 17% response rate, including 1 complete response, with only mild myelosuppression. This Phase II study (CALGB 9031) was conducted to determine the effectiveness of and toxicities that would result from adding cisplatin to DHAC administered to the same patient population. METHODS, Thirty-six patients were treated with concurrent DHAC at 1500 mg/m(2)/day for 5 days by continuous infusion and cisplatin 15 mg/m(2) daily for 5 days. Therapy was repeated every 3 weeks. Cisplatin was to be increased to 20 mg/m(2) daily in subsequent cycles if toxicity was minimal. Therapy was continued until disease progression or excessive toxicity mandated discontinuation. RESULTS, Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17%). The median duration of response was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was significant chest/pericardial pain, as was observed with DHAC alone. There were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively. Significant leukopenia was observed in 29% of patients, but there were no neutropenic fevers. CONCLUSIONS. The addition of cisplatin to DHAC did not increase the response rate over that observed with DHAC alone in patients with mesothelioma; however, it did increase toxicity, especially leukopenia. This combination is not recommended for further studies involving mesothelioma patients. (C) 1998 American Cancer Society. C1 Lutheran Gen Hosp, Pk Ridge, IL 60068 USA. CALGB Stat Off, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Canc Inst New Jersey, New Brunswick, NJ USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mt Sinai Hosp, New York, NY 10029 USA. Univ S Carolina, Charleston, SC USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. RP Samuels, BL (reprint author), Lutheran Gen Canc Ctr, 1700 Luther Lane, Pk Ridge, IL 60068 USA. FU NCI NIH HHS [CA 33601, CA 31946, CA 12449] NR 34 TC 48 Z9 49 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 1998 VL 82 IS 8 BP 1578 EP 1584 PG 7 WC Oncology SC Oncology GA ZF580 UT WOS:000072911700021 PM 9554537 ER PT J AU Jussila, L Valtola, R Partanen, TA Salven, P Heikkila, P Matikainen, MT Renkonen, R Kaipainen, A Detmar, M Tschachler, E Alitalo, R Alitalo, K AF Jussila, L Valtola, R Partanen, TA Salven, P Heikkila, P Matikainen, MT Renkonen, R Kaipainen, A Detmar, M Tschachler, E Alitalo, R Alitalo, K TI Lymphatic endothelium and Kaposi's sarcoma spindle cells detected by antibodies against the vascular endothelial growth factor receptor-3 SO CANCER RESEARCH LA English DT Article ID EXPRESSION; DIFFERENTIATION; FLT4 AB Lymphatic vessels have been difficult to study in detail in normal and tumor tissues because of the lack of molecular markers. sere, monoclonal antibodies against the extracellular domain of the vascular endothelial growth factor-C receptor that we have named VEGFR-3 were found to specifically stain endothelial cells of lymphatic vessels and vessels around tumors such as lymphoma and in situ breast carcinoma, Interestingly, the spindle cells of several cutaneous nodular AIDS-associated Kaposi's sarcomas and the endothelium around the nodules were also VEGFR-3 positive. The first specific molecular marker for the lymphatic endothelium should provide a useful tool for the analysis of lymphatic vessels in malignant tumors and their metastases and the cellular origin and differentiation of Kaposi's sarcomas. C1 Univ Helsinki, Mol Canc Biol Lab, Haartman Inst, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Pathol, Haartman Inst, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Bacteriol & Immunol, Haartman Inst, FIN-00014 Helsinki, Finland. Univ Helsinki, Transplantat Lab, Haartman Inst, FIN-00014 Helsinki, Finland. Univ Turku, Ctr Biotechnol, FIN-20520 Turku, Finland. Univ Helsinki, Cent Hosp, Dept Oncol, FIN-00290 Helsinki, Finland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Vienna, Dept Dermatol, A-1090 Vienna, Austria. RP Alitalo, K (reprint author), Univ Helsinki, Mol Canc Biol Lab, Haartman Inst, FIN-00014 Helsinki, Finland. RI Alitalo, Kari/J-5013-2014 OI Alitalo, Kari/0000-0002-7331-0902 NR 24 TC 229 Z9 239 U1 0 U2 3 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 APR 15 PY 1998 VL 58 IS 8 BP 1599 EP 1604 PG 6 WC Oncology SC Oncology GA ZH644 UT WOS:000073132600005 PM 9563467 ER PT J AU Tsai, FY Browne, CP Orkin, SH AF Tsai, FY Browne, CP Orkin, SH TI Knock-in mutation of transcription factor GATA-3 into the GATA-1 locus: Partial rescue of GATA-1 loss of function in erythroid cells SO DEVELOPMENTAL BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; DNA-BINDING; MEGAKARYOCYTIC DIFFERENTIATION; ZINC-FINGER; GENE; FAMILY; EXPRESSION; LINEAGE; MICE; PRECURSORS AB Transcription factors of the GATA-family are essential for proper development of diverse tissues or cell types. GATA-1 is required for differentiation of two hematopoietic lineages (red blood cells and megakaryocytes), whereas GATA-3 is essential for T-cell development. Functional studies suggest that many properties of the GATA-family of proteins are shared and Largely interchangeable. To test whether the function of GATA-1 in erythroid differentiation can be replaced by another GATA-factor, we generated a knock-in mutation of the GATA-1 locus in which GATA-3 cDNA was introduced by gene targeting. Mutant embryos (designated G1G(3ki)), though embryonic lethal, exhibit partial rescue, characterized by increased survival of erythroid precursor cells and improved hemoglobin production. The basis for the incomplete extent of rescue is likely to be complex, but may be accounted for, in part, by insufficient accumulation of GATA-3 protein (compared with the normal level of GATA-1). Our findings suggest that GATA-3 protein is functional when expressed in an erythroid environment and is competent to act on at least a subset of erythroid-expressed target genes in vivo. (C) 1998 Academic Press. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Tsai, FY (reprint author), Millennium Pharmaceut Inc, Boston, MA 02205 USA. NR 41 TC 50 Z9 53 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 1998 VL 196 IS 2 BP 218 EP 227 DI 10.1006/dbio.1997.8842 PG 10 WC Developmental Biology SC Developmental Biology GA ZM075 UT WOS:000073502200008 PM 9576834 ER PT J AU Rapoport, I Chen, YC Cupers, P Shoelson, SE Kirchhausen, T AF Rapoport, I Chen, YC Cupers, P Shoelson, SE Kirchhausen, T TI Dileucine-based sorting signals bind to the beta chain of AP-1 at a site distinct and regulated differently from the tyrosine-based motif-binding site SO EMBO JOURNAL LA English DT Article DE coated vesicles; endocytosis; exocytosis; receptor sorting ID PROTEIN COMPLEX AP-2; FACTOR-II RECEPTOR; HIGH-AFFINITY INTERACTION; GOLGI ASSEMBLY PROTEINS; COATED VESICLE ADAPTERS; GROWTH-FACTOR RECEPTOR; DI-LEUCINE MOTIF; CYTOPLASMIC DOMAIN; PLASMA-MEMBRANE; PHOSPHATIDYLINOSITOL 3-KINASE AB In previous work, we showed that peptides from endocytosed proteins containing the tyrosine YXX phi sorting motif are recognized by the mu 2 subunit of AP-2, the plasma membrane clathrin adaptor protein complex. This interaction is activated phosphoinositide lipids that are phosphorylated at the D-3 position of the inositol ring, and is also enhanced by the formation of clathrin-AP-2 coats, Here, we describe the detection of a specific interaction between peptides containing a second sorting motif, the dileucine motif, and AP-1, the clathrin adaptor complex responsible for sorting proteins at the trans-Golgi network (TGN). Surprisingly the site of dileucine binding is the beta 1 subunit, not mu 1. A YXX phi-containing peptide from a protein trafficked within the TGN does bind to mu 1, however. Phosphatidylinositol 3,4-diphosphate and 3,4,5-triphosphate did not activate the interaction between dileucine-containing peptides and AP-1 but instead inhibited it, and clathrin-AP-1 coat formation did not alter the interaction, Thus, there are at least two physically separate binding sites far sorting signals on APs, which are also regulated independently. 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, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK43123]; NIGMS NIH HHS [GM36548] NR 53 TC 244 Z9 248 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 15 PY 1998 VL 17 IS 8 BP 2148 EP 2155 DI 10.1093/emboj/17.8.2148 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZJ871 UT WOS:000073262100002 PM 9545228 ER PT J AU Aranda, R Byrne, FR Panwala, C Yakoub, G Sydora, BC Targan, SR Kronenberg, M AF Aranda, R Byrne, FR Panwala, C Yakoub, G Sydora, BC Targan, SR Kronenberg, M TI CD4+ cells found in the inflamed colon of SCID mice with colitis are oligoclonal. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3778 BP A921 EP A921 DI 10.1016/S0016-5085(98)83753-0 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603752 ER PT J AU Ashida, T Frederick, D Takahashi, H AF Ashida, T Frederick, D Takahashi, H TI Production of Th1 helper T cell associated cytokine, interleukin-18 in human colonic epithelial cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3788 BP A924 EP A924 DI 10.1016/S0016-5085(98)83763-3 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603766 ER PT J AU Awane, M MacDermott, RP Podolsky, DK Reinecker, HC AF Awane, M MacDermott, RP Podolsky, DK Reinecker, HC TI IL-17 regulates the activation of three distinct MAP-kinase families in intestinal epithelial cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Lahey Hitchcock Clin, Burlington, MA 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4606 BP A1125 EP A1125 DI 10.1016/S0016-5085(98)84576-9 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604576 ER PT J AU Awane, M Andres, PG MacDermott, RP Podolsky, DK Reinecker, HC AF Awane, M Andres, PG MacDermott, RP Podolsky, DK Reinecker, HC TI IL-17 synergizes with IL-1 beta in the induction of chemokine expression in intestinal epithelial cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Lahey Hitchcock Clin, Burlington, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3789 BP A924 EP A924 DI 10.1016/S0016-5085(98)83764-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603763 ER PT J AU Ayub, K Anderson, S Anand, BS AF Ayub, K Anderson, S Anand, BS TI Response of chronic alcoholics with hepatitis C virus infection to interferon therapy: Preliminary results. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Dept Med, Houston, TX 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0032 BP A1206 EP A1206 DI 10.1016/S0016-5085(98)84894-4 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604892 ER PT J AU Bate, GW Varro, A Dimaline, R Wang, TC Koh, TJ Dockray, GJ AF Bate, GW Varro, A Dimaline, R Wang, TC Koh, TJ Dockray, GJ TI Enterochromaffin-like (ECL) cell function in transgenic mice expressing gastrin in pancreatic beta-cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4611 BP A1127 EP A1127 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604581 ER PT J AU Beck, PL Xavier, RJ Lu, NF Podolsky, DK Seed, B AF Beck, PL Xavier, RJ Lu, NF Podolsky, DK Seed, B TI Targeted disruption of E-, P- and L-selectin ligand biosynthesis is associated with a decrease in susceptibility to indomethacin-induced intestinal damage. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biol Mol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0284 BP A70 EP A70 DI 10.1016/S0016-5085(98)80282-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600282 ER PT J AU Belkind-Gerson, J Choi, R Kaplan, LM AF Belkind-Gerson, J Choi, R Kaplan, LM TI Neurotrophin 3 (NT-3) is required for differentiation of intestinal mucosal neurons and innervation of epithelial cells in culture. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4615 BP A1128 EP A1128 DI 10.1016/S0016-5085(98)84585-X PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604585 ER PT J AU Brandwein, SL Reinecker, HC Podolsky, DK AF Brandwein, SL Reinecker, HC Podolsky, DK TI LPS induces upregulation of CD14 expression and tyrosine phosphorylation of a 40 KD protein in an intestinal epithelial cell line. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3855 BP A941 EP A941 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603829 ER EF