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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2000
    In:  Neurology Vol. 55, No. 2 ( 2000-07-25), p. 289-293
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. 2 ( 2000-07-25), p. 289-293
    Abstract: Objective: To examine the shorthand publications of Sir William Richard Gowers. Background: Gowers developed an almost obsessional interest in Pitman shorthand. During the later part of his active career (1894–1910), the bulk of his professional writing, comprising nearly 100 articles, was printed entirely in Pitman shorthand in the Phonographic Record of Clinical Teaching and Medical Science . The obscurity and rarity of this periodical, and the increasingly arcane nature of Pitman shorthand, has left the bulk of these articles “buried in obscurity and locked up in code” (M. Critchley, 1949). Design/Methods: A complete set of Gowers’ shorthand publications as listed in his standard bibliography was compiled. Transcription of the Pitman shorthand outlines was performed by a qualified Pitman shorthand transcriber and verified using the contemporaneous Phonographic Outlines of Medical Terms (1902) as an authoritative guide. Results: The first transcription of Gowers’ shorthand publications has now been completed. The history of Gowers’ interest in shorthand and his efforts to proselytize the medical profession is reviewed. Selected excerpts are presented from his shorthand articles, which include papers devoted to problems in practical diagnosis, notes on clinical teaching, and the shorthand transcriptions of his lectures at Queen Square and at University College Hospital on such diverse subjects as myelitis, neurosyphilis, polio, muscular dystrophy, tumors, vascular disease, epilepsy, and the nervous system in old age. Conclusions: The previously unpublished transcriptions of his shorthand articles represent a major and previously inaccessible part of Gowers’ neurologic opus. These articles exemplify Gowers as a practicing neurologist and teacher, and significantly expand our insights into one of neurology’s most significant and influential figures.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2000
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  • 2
    Online Resource
    Online Resource
    American Society for Microbiology ; 2002
    In:  Journal of Virology Vol. 76, No. 6 ( 2002-03-15), p. 2585-2594
    In: Journal of Virology, American Society for Microbiology, Vol. 76, No. 6 ( 2002-03-15), p. 2585-2594
    Abstract: Mammalian reovirus infection results in perturbation of host cell cycle progression. Since reovirus infection is known to activate cellular transcription factors, we investigated alterations in cell cycle-related gene expression following HEK293 cell infection by using the Affymetrix U95A microarray. Serotype 3 reovirus infection results in differential expression of 10 genes classified as encoding proteins that function at the G 1 -to-S transition, 11 genes classified as encoding proteins that function at G 2 -to-M transition, and 4 genes classified as encoding proteins that function at the mitotic spindle checkpoint. Serotype 1 reovirus infection results in differential expression of four genes classified as encoding proteins that function at the G 1 -to-S transition and three genes classified as encoding proteins that function at G 2 -to-M transition but does not alter any genes classified as encoding proteins that function at the mitotic spindle checkpoint. We have previously shown that serotype 3, but not serotype 1, reovirus infection induces a G 2 -to-M transition arrest resulting from an inhibition of cdc2 kinase activity. Of the differentially expressed genes encoding proteins regulating the G 2 -to-M transition, chk1, wee1, and GADD45 are known to inhibit cdc2 kinase activity. A hypothetical model describing serotype 3 reovirus-induced inhibition of cdc2 kinase is presented, and reovirus-induced perturbations of the G 1 -to-S, G 2 -to-M, and mitotic spindle checkpoints are discussed.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2002
    detail.hit.zdb_id: 1495529-5
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  • 3
    Online Resource
    Online Resource
    American Society for Microbiology ; 2001
    In:  Journal of Virology Vol. 75, No. 1 ( 2001-01), p. 351-361
    In: Journal of Virology, American Society for Microbiology, Vol. 75, No. 1 ( 2001-01), p. 351-361
    Abstract: Viral myocarditis is an important cause of human morbidity and mortality for which reliable and effective therapy is lacking. Using reovirus strain 8B infection of neonatal mice, a well-characterized experimental model of direct virus-induced myocarditis, we now demonstrate that myocardial injury results from apoptosis. Proteases play a critical role as effectors of apoptosis. The activity of the cysteine protease calpain increases in reovirus-infected myocardiocytes and can be inhibited by the dipeptide alpha-ketoamide calpain inhibitor Z -Leu-aminobutyric acid-CONH(CH 2 )3-morpholine (CX295). Treatment of reovirus-infected neonatal mice with CX295 protects them against reovirus myocarditis as documented by (i) a dramatic reduction in histopathologic evidence of myocardial injury, (ii) complete inhibition of apoptotic myocardial cell death as identified by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling, (iii) a reduction in serum creatine phosphokinase, and (iv) improved weight gain. These findings are the first evidence for the importance of a calpain-associated pathway of apoptotic cell death in viral disease. Inhibition of apoptotic signaling pathways may be an effective strategy for the treatment of viral disease in general and viral myocarditis in particular.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2001
    detail.hit.zdb_id: 1495529-5
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  • 4
    In: Journal of Virology, American Society for Microbiology, Vol. 77, No. 16 ( 2003-08-15), p. 8934-8947
    Abstract: Reoviruses are a leading model for understanding cellular mechanisms of virus-induced apoptosis. Reoviruses induce apoptosis in multiple cell lines in vitro, and apoptosis plays a key role in virus-induced tissue injury of the heart and brain in vivo. The activation of transcription factors NF-κB and c-Jun are key events in reovirus-induced apoptosis, indicating that new gene expression is critical to this process. We used high-density oligonucleotide microarrays to analyze cellular transcriptional alterations in HEK293 cells after infection with reovirus strain T3A (i.e., apoptosis inducing) compared to infection with reovirus strain T1L (i.e., minimally apoptosis inducing) and uninfected cells. These strains also differ dramatically in their potential to induce apoptotic injury in hearts of infected mice in vivo—T3A is myocarditic, whereas T1L is not. Using high-throughput microarray analysis of over 12,000 genes, we identified differential expression of a defined subset of genes involved in apoptosis and DNA repair after reovirus infection. This provides the first comparative analysis of altered gene expression after infection with viruses of differing apoptotic phenotypes and provides insight into pathogenic mechanisms of virus-induced disease.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2003
    detail.hit.zdb_id: 1495529-5
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  • 5
    Online Resource
    Online Resource
    American Society for Microbiology ; 2004
    In:  Clinical Microbiology Reviews Vol. 17, No. 4 ( 2004-10), p. 903-925
    In: Clinical Microbiology Reviews, American Society for Microbiology, Vol. 17, No. 4 ( 2004-10), p. 903-925
    Abstract: Hundreds of viruses cause central nervous system (CNS) disease, including meningoencephalitis and postinfectious encephalomyelitis, in humans. The cerebrospinal fluid (CSF) is abnormal in 〉 90% of cases; however, routine CSF studies only rarely lead to identification of a specific etiologic agent. Diagnosis of viral infections of the CNS has been revolutionized by the advent of new molecular diagnostic technologies to amplify viral nucleic acid from CSF, including PCR, nucleic acid sequence-based amplification, and branched-DNA assay. PCR is ideally suited for identifying fastidious organisms that may be difficult or impossible to culture and has been widely applied for detection of both DNA and RNA viruses in CSF. The technique can be performed rapidly and inexpensively and has become an integral component of diagnostic medical practice in the United States and other developed countries. In addition to its use for identification of etiologic agents of CNS disease in the clinical setting, PCR has also been used to quantitate viral load and monitor duration and adequacy of antiviral drug therapy. PCR has also been applied in the research setting to help discriminate active versus postinfectious immune-mediate disease, identify determinants of drug resistance, and investigate the etiology of neurologic disease of uncertain cause. This review discusses general principles of PCR and reverse transcription-PCR, including qualitative, quantitative, and multiplex techniques, with comment on issues of sensitivity, specificity, and positive and negative predictive values. The application of molecular diagnostic methods for diagnosis of specific infectious entities is reviewed in detail, including viruses for which PCR is of proven efficacy and is widely available, viruses for which PCR is less widely available or for which PCR has unproven sensitivity and specificity, and nonviral entities which can mimic viral CNS disease.
    Type of Medium: Online Resource
    ISSN: 0893-8512 , 1098-6618
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
    detail.hit.zdb_id: 1497041-7
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    American Society for Microbiology ; 2000
    In:  Journal of Virology Vol. 74, No. 17 ( 2000-09), p. 8135-8139
    In: Journal of Virology, American Society for Microbiology, Vol. 74, No. 17 ( 2000-09), p. 8135-8139
    Abstract: Members of the tumor necrosis factor (TNF) receptor superfamily and their activating ligands transmit apoptotic signals in a variety of systems. We now show that the binding of TNF-related, apoptosis-inducing ligand (TRAIL) to its cellular receptors DR5 (TRAILR2) and DR4 (TRAILR1) mediates reovirus-induced apoptosis. Anti-TRAIL antibody and soluble TRAIL receptors block reovirus-induced apoptosis by preventing TRAIL-receptor binding. In addition, reovirus induces both TRAIL release and an increase in the expression of DR5 and DR4 in infected cells. Reovirus-induced apoptosis is also blocked following inhibition of the death receptor-associated, apoptosis-inducing molecules FADD (for FAS-associated death domain) and caspase 8. We propose that reovirus infection promotes apoptosis via the expression of DR5 and the release of TRAIL from infected cells. Virus-induced regulation of the TRAIL apoptotic pathway defines a novel mechanism for virus-induced apoptosis.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2000
    detail.hit.zdb_id: 1495529-5
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  • 7
    Online Resource
    Online Resource
    American Society for Microbiology ; 2004
    In:  Journal of Virology Vol. 78, No. 20 ( 2004-10-15), p. 11040-11050
    In: Journal of Virology, American Society for Microbiology, Vol. 78, No. 20 ( 2004-10-15), p. 11040-11050
    Abstract: Viral myocarditis is a disease with a high morbidity and mortality. The pathogenesis of this disease remains poorly characterized, with components of both direct virus-mediated and secondary inflammatory and immune responses contributing to disease. Apoptosis has increasingly been viewed as an important mechanism of myocardial injury in noninfectious models of cardiac disease, including ischemia and failure. Using a reovirus murine model of viral myocarditis, we characterized and targeted apoptosis as a key mechanism of virus-associated myocardial injury in vitro and in vivo. We demonstrated caspase-3 activation, in conjunction with terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and annexin binding, in cardiac myocytes after myocarditic viral infection in vitro. We also demonstrated a tight temporal and geographical correlation between caspase-3 activation, histologic injury, and viral load in cardiac tissue after myocarditic viral infection in vivo. Two pharmacologic agents that broadly inhibit caspase activity, Q-VD-OPH and Z-VAD(OMe)-FMK, effectively inhibited virus-induced cellular death in vitro. The inhibition of caspase activity in vivo by the use of pharmacologic agents as well as genetic manipulation reduced virus-induced myocardial injury by 40 to 60% and dramatically improved survival in infected caspase-3-deficient animals. This study indicates that apoptosis plays a critical role in mediating cardiac injury in the setting of viral myocarditis and is the first demonstration that caspase inhibition may serve as a novel therapeutic strategy for this devastating disease.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
    detail.hit.zdb_id: 1495529-5
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  • 8
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2001
    In:  Oncogene Vol. 20, No. 47 ( 2001-10-18), p. 6910-6919
    In: Oncogene, Springer Science and Business Media LLC, Vol. 20, No. 47 ( 2001-10-18), p. 6910-6919
    Type of Medium: Online Resource
    ISSN: 0950-9232 , 1476-5594
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2001
    detail.hit.zdb_id: 2008404-3
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  • 9
    Online Resource
    Online Resource
    Wiley ; 2001
    In:  Brain Pathology Vol. 11, No. 4 ( 2001-10), p. 452-464
    In: Brain Pathology, Wiley, Vol. 11, No. 4 ( 2001-10), p. 452-464
    Type of Medium: Online Resource
    ISSN: 1015-6305
    Language: English
    Publisher: Wiley
    Publication Date: 2001
    detail.hit.zdb_id: 2029927-8
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  • 10
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2002
    In:  The Journal of Infectious Diseases Vol. 186, No. 11 ( 2002-12), p. 1547-1557
    In: The Journal of Infectious Diseases, Oxford University Press (OUP), Vol. 186, No. 11 ( 2002-12), p. 1547-1557
    Type of Medium: Online Resource
    ISSN: 0022-1899 , 1537-6613
    URL: Issue
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2002
    detail.hit.zdb_id: 1473843-0
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