Borna disease virus (BDV) was previously believed to have a strict tropism for the nervous system... more Borna disease virus (BDV) was previously believed to have a strict tropism for the nervous system. BDV has recently been identified by a reverse transcription-polymerization chain reaction-enzyme immunosorbent assay (RT-PCR-EIA) in bone marrow cells and peripheral blood mononuclear cells (PBMC) in BDV-infected Lewis rats. We now report the identification of BDV RNA and infectious virus in thymus cells from rats infected either as neonates (PTI-NB) or as adults (4 weeks of age). Based on in vitro studies, we determined that the BDV-infected cells in bone marrow and thymus tissue are fibroblastic stromal cells. Bone marrow stromal cells are nonhematopoietic, fixed-tissue elements that support hematopoiesis, and, thus, it was not surprising that BDV infection altered the recovery from granulocytopenia and leukocytopenia after myelosuppressive treatment. Notably, unlike other immunotropic and neurotropic viruses, BDV does not appear to infect cells of myeloid or lymphoid lineages. We al...
The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric d... more The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune ...
Abstract: Borna disease virus (BDV) is a neurotropic agent that causes CNS immunopathology and in... more Abstract: Borna disease virus (BDV) is a neurotropic agent that causes CNS immunopathology and infects a wide range of natural hosts including cattle, rabbits, goats, deer, llamas, alpacas, horses, sheep, ostriches, domestic cats and possibly man. BDV sequence detection and virus recovery have been recently reported in humans; however, BDV is not as yet established as a human pathogen. In previous studies of BDV serology in schizophrenia, we found anti-BDV seropositivity to occur at a relatively high rate and to be ...
Semistructured interviews with 28 schizophrenic patients were videotaped. The affective flattenin... more Semistructured interviews with 28 schizophrenic patients were videotaped. The affective flattening section of the Scale for the Assessment of Negative Symptoms (SANS) was rated after each interview. At a later date, each videotape was rated by three raters as well as the interviewer. Reliability was estimated within and across rating conditions by intraclass correlation. Comparison of reliability scores across rating conditions indicated that the videotape medium had little effect on the ability of raters to rate affective flattening similarly.
Consensus exercises have identified and prioritized domains of measurement for studies in acute a... more Consensus exercises have identified and prioritized domains of measurement for studies in acute and chronic gout. In parallel, the technical properties of instruments for measurement in many of these domains have been assessed, with the main objective to consider the instruments in the context of the OMERACT filter of truth, discrimination, and feasibility. These data were presented and discussed at OMERACT 9 in the gout workshop, in breakout groups, and at informal meetings of the gout group. In acute gout, instruments for domains of pain, joint swelling, joint tenderness, and patient and physician global assessment have been assessed. In chronic gout, some validation exercises have been performed in instruments for domains serum urate, tophus measurement, health-related quality of life (HRQOL). In voting at OMERACT 9, the Medical Outcomes Study Short-Form 36 was endorsed as a valid instrument for measurement of HRQOL. Methods of tophus measurement were considered to have met some ...
Discussion and voting at OMERACT 9 confirmed 5 essential domains for outcomes of acute gout: pain... more Discussion and voting at OMERACT 9 confirmed 5 essential domains for outcomes of acute gout: pain, joint swelling, joint tenderness, patient global assessment and activity limitations. For studies in chronic gout 7 essential domains are: serum urate, acute gout attacks, tophus burden, health-related quality of life, activity limitations, pain, and patient global assessment. Implications of patient perspectives, discretionary domains for specific studies, measurement instruments and a possible responder index are under study.
To identify, in people known to have gout, the testable, key components of a standard definition ... more To identify, in people known to have gout, the testable, key components of a standard definition of gout flare for use in clinical research. Consensus methodology was used to identify key elements of a gout flare. Two Delphi exercises were conducted among different groups of rheumatologists. A cognitive mapping technique among 9 gout experts with hierarchical cluster analysis provided a framework to guide the panel discussion, which identified the final set of items that should be tested empirically. From the Delphi exercises, 21 items were presented to the expert panel. Cluster analysis and multidimensional scaling showed that these items clustered into 5 concepts (joint inflammation, severity of symptoms, stereotypical nature, pain, and gout archetype) distributed along 2 dimensions (objective to subjective features and general features to specific features of gout). Using this analysis, expert panel discussion generated a short list of potential features: joint swelling, joint tenderness, joint warmth, severity of pain, patient global assessment, time to maximum pain, time to complete resolution of pain, an acute-phase marker, and functional impact of the episode. A short list of features has been identified and now requires validation against a patient- and physician-defined gout flare in order to determine the best combination of features.
ObjectiveTo assess the efficacy of pegloticase in achieving and maintaining plasma urate levels o... more ObjectiveTo assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of <6 mg/dl in gout patients in whom other treatments have failed, and to assess the pharmacokinetics and safety of pegloticase.MethodsForty‐one patients were randomized to undergo 12–14 weeks of treatment with pegloticase at 1 of 4 dosage levels: 4 mg every 2 weeks, 8 mg every 2 weeks, 8 mg every 4 weeks, or 12 mg every 4 weeks. Plasma uricase activity, plasma urate, and antipegloticase antibodies were measured, pharmacokinetic parameters were assessed, and adverse events were recorded.ResultsThe mean plasma urate level was reduced to ≤6 mg/dl within 6 hours in all dosage groups, and this was sustained throughout the treatment period in the 8 mg and 12 mg dosage groups. The most effective dosage was 8 mg every 2 weeks. Twenty‐six patients received all protocol doses. The percentage of the patients in whom the primary efficacy end point (plasma urate <6 mg/dl for 80% of the study pe...
Persistent hyperuricemia (defined as a serum urate level &gt;6 mg/dl) may lead to chronic top... more Persistent hyperuricemia (defined as a serum urate level &gt;6 mg/dl) may lead to chronic tophaceous gout, which is characterized by acute gouty arthritis, gouty arthropathy, and tophaceous deposits in articular, periarticular, and subcutaneous tissues (1). Tophaceous deposits may lead to ...
Borna disease virus (BDV) was previously believed to have a strict tropism for the nervous system... more Borna disease virus (BDV) was previously believed to have a strict tropism for the nervous system. BDV has recently been identified by a reverse transcription-polymerization chain reaction-enzyme immunosorbent assay (RT-PCR-EIA) in bone marrow cells and peripheral blood mononuclear cells (PBMC) in BDV-infected Lewis rats. We now report the identification of BDV RNA and infectious virus in thymus cells from rats infected either as neonates (PTI-NB) or as adults (4 weeks of age). Based on in vitro studies, we determined that the BDV-infected cells in bone marrow and thymus tissue are fibroblastic stromal cells. Bone marrow stromal cells are nonhematopoietic, fixed-tissue elements that support hematopoiesis, and, thus, it was not surprising that BDV infection altered the recovery from granulocytopenia and leukocytopenia after myelosuppressive treatment. Notably, unlike other immunotropic and neurotropic viruses, BDV does not appear to infect cells of myeloid or lymphoid lineages. We al...
The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric d... more The prevalence of Borna disease virus (BDV)-specific antibodies among patients with psychiatric disorders and healthy individuals has varied in several reports using several different serological assay methods. A reliable and specific method for anti-BDV antibodies needs to be developed to clarify the pathological significance of BDV infections in humans. We developed a new electrochemiluminescence immunoassay (ECLIA) for the antibody to BDV that uses two recombinant proteins of BDV, p40 and p24 (full length). Using this ECLIA, we examined 3,476 serum samples from humans with various diseases and 917 sera from blood donors in Japan for the presence of anti-BDV antibodies. By ECLIA, 26 (3.08%) of 845 schizophrenia patients and 9 (3.59%) of 251 patients with mood disorders were seropositive for BDV. Among 323 patients with other psychiatric diseases, 114 with neurological diseases, 75 with chronic fatigue syndrome, 85 human immunodeficiency virus-infected patients, 50 with autoimmune ...
Abstract: Borna disease virus (BDV) is a neurotropic agent that causes CNS immunopathology and in... more Abstract: Borna disease virus (BDV) is a neurotropic agent that causes CNS immunopathology and infects a wide range of natural hosts including cattle, rabbits, goats, deer, llamas, alpacas, horses, sheep, ostriches, domestic cats and possibly man. BDV sequence detection and virus recovery have been recently reported in humans; however, BDV is not as yet established as a human pathogen. In previous studies of BDV serology in schizophrenia, we found anti-BDV seropositivity to occur at a relatively high rate and to be ...
Semistructured interviews with 28 schizophrenic patients were videotaped. The affective flattenin... more Semistructured interviews with 28 schizophrenic patients were videotaped. The affective flattening section of the Scale for the Assessment of Negative Symptoms (SANS) was rated after each interview. At a later date, each videotape was rated by three raters as well as the interviewer. Reliability was estimated within and across rating conditions by intraclass correlation. Comparison of reliability scores across rating conditions indicated that the videotape medium had little effect on the ability of raters to rate affective flattening similarly.
Consensus exercises have identified and prioritized domains of measurement for studies in acute a... more Consensus exercises have identified and prioritized domains of measurement for studies in acute and chronic gout. In parallel, the technical properties of instruments for measurement in many of these domains have been assessed, with the main objective to consider the instruments in the context of the OMERACT filter of truth, discrimination, and feasibility. These data were presented and discussed at OMERACT 9 in the gout workshop, in breakout groups, and at informal meetings of the gout group. In acute gout, instruments for domains of pain, joint swelling, joint tenderness, and patient and physician global assessment have been assessed. In chronic gout, some validation exercises have been performed in instruments for domains serum urate, tophus measurement, health-related quality of life (HRQOL). In voting at OMERACT 9, the Medical Outcomes Study Short-Form 36 was endorsed as a valid instrument for measurement of HRQOL. Methods of tophus measurement were considered to have met some ...
Discussion and voting at OMERACT 9 confirmed 5 essential domains for outcomes of acute gout: pain... more Discussion and voting at OMERACT 9 confirmed 5 essential domains for outcomes of acute gout: pain, joint swelling, joint tenderness, patient global assessment and activity limitations. For studies in chronic gout 7 essential domains are: serum urate, acute gout attacks, tophus burden, health-related quality of life, activity limitations, pain, and patient global assessment. Implications of patient perspectives, discretionary domains for specific studies, measurement instruments and a possible responder index are under study.
To identify, in people known to have gout, the testable, key components of a standard definition ... more To identify, in people known to have gout, the testable, key components of a standard definition of gout flare for use in clinical research. Consensus methodology was used to identify key elements of a gout flare. Two Delphi exercises were conducted among different groups of rheumatologists. A cognitive mapping technique among 9 gout experts with hierarchical cluster analysis provided a framework to guide the panel discussion, which identified the final set of items that should be tested empirically. From the Delphi exercises, 21 items were presented to the expert panel. Cluster analysis and multidimensional scaling showed that these items clustered into 5 concepts (joint inflammation, severity of symptoms, stereotypical nature, pain, and gout archetype) distributed along 2 dimensions (objective to subjective features and general features to specific features of gout). Using this analysis, expert panel discussion generated a short list of potential features: joint swelling, joint tenderness, joint warmth, severity of pain, patient global assessment, time to maximum pain, time to complete resolution of pain, an acute-phase marker, and functional impact of the episode. A short list of features has been identified and now requires validation against a patient- and physician-defined gout flare in order to determine the best combination of features.
ObjectiveTo assess the efficacy of pegloticase in achieving and maintaining plasma urate levels o... more ObjectiveTo assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of <6 mg/dl in gout patients in whom other treatments have failed, and to assess the pharmacokinetics and safety of pegloticase.MethodsForty‐one patients were randomized to undergo 12–14 weeks of treatment with pegloticase at 1 of 4 dosage levels: 4 mg every 2 weeks, 8 mg every 2 weeks, 8 mg every 4 weeks, or 12 mg every 4 weeks. Plasma uricase activity, plasma urate, and antipegloticase antibodies were measured, pharmacokinetic parameters were assessed, and adverse events were recorded.ResultsThe mean plasma urate level was reduced to ≤6 mg/dl within 6 hours in all dosage groups, and this was sustained throughout the treatment period in the 8 mg and 12 mg dosage groups. The most effective dosage was 8 mg every 2 weeks. Twenty‐six patients received all protocol doses. The percentage of the patients in whom the primary efficacy end point (plasma urate <6 mg/dl for 80% of the study pe...
Persistent hyperuricemia (defined as a serum urate level &gt;6 mg/dl) may lead to chronic top... more Persistent hyperuricemia (defined as a serum urate level &gt;6 mg/dl) may lead to chronic tophaceous gout, which is characterized by acute gouty arthritis, gouty arthropathy, and tophaceous deposits in articular, periarticular, and subcutaneous tissues (1). Tophaceous deposits may lead to ...
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