Coexisting SLE and HIV infection.
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Comorbidity↗
Biomedical subjects
S Hirohata
Publications and source records attributed to S Hirohata.
[Quantitative determination of serum anti ribosomal-P protein antibody by enzyme immunoassay].
An enzyme immunoassay for serum anti-ribosomal P protein antibodies (anti-P) is developed, using highly purified synthetic ribosomal P peptides of the carboxyl terminal 22 amino acid sequence conjugated to human serum albumin (HSA) as an antigen. Anti-P levels were determined by subtracting the nonspecific binding activities to HSA. The concentration of anti-P which produced half of the maximal absorbance at 492 nm (OD492) given by saturating concentrations of anti-P in the ELISA plate was defined as 1 U/ml. The anti-P values in the samples were determined by referring to a standard curve made from a standard serum containing anti-P. Serum anti-P levels in 34 normal individuals were 5.52 +/- 8.39 U/ml (mean +/- SD). Anti-P in sera from 45 patients with systemic lupus erythematosus (SLE), 24 patients with rheumatoid arthritis (RA) and 27 patients with Behçet's disease were also analyzed. The values for serum anti-P in SLE, RA and Behçet's disease groups were 251.04 +/- 843.07 U/ml, 5.97 +/- 15.18 U/ml, and 2.62 +/- 3.35 U/ml (mean +/- SD) respectively. The positive ratio for serum anti-P in SLE patients was significantly higher than that in patients with RA or Behçet's disease (p < 0.05 as determined by chi-square test). These results indicate that quantitative determination of serum anti-P by our enzyme immunoassay is a successful tool for the diagnosis of SLE.
Adult↗
[Coping with pathological changes in nerves and blood vessels in collagen disease--CNS lupus].
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Anti-Inflammatory Agents↗
Accelerated generation of CD14+ monocyte-lineage cells from the bone marrow of rheumatoid arthritis patients.
OBJECTIVE: To examine the capacity of bone marrow progenitor cells to generate CD14+ cells, in order to assess the role of bone marrow in the pathogenesis of rheumatoid arthritis (RA). METHODS: CD14- cells purified from bone marrow specimens of 11 patients with active RA and 8 control patients (osteoarthritis or trauma) were cultured in the presence or absence of granulocyte-macrophage colony-stimulating factor (GM-CSF; 100 pg/ml). After incubation for various lengths of time, the cells were analyzed by flow cytometry for expression of CD14 and HLA-DR. RESULTS: The spontaneous generation of CD14+ cells from bone marrow CD14- progenitor cells was accelerated in RA patients compared with control patients. Moreover, the expression of HLA-DR on the bone marrow-derived CD14+ cells was also accelerated in RA patients compared with controls. GM-CSF significantly enhanced the generation of CD14+ cells, as well as the expression of HLA-DR, on CD14+ cells of control patients, but not those of RA patients. GM-CSF levels in the culture supernatants of bone marrow CD14- cells were not significantly different between RA patients and control patients (undetectable in most cases). CONCLUSION: These observations strongly support the hypothesis that the accelerated generation of CD14+ cells from bone marrow progenitor cells and the accelerated maturation of such CD14+ cells into HLA-DR+ cells play an important role in the pathogenesis of RA. Moreover, the data suggest a functional alteration of RA bone marrow CD14- cells in their responsiveness to GM-CSF.
Adult↗
Association of anti-ribosomal P protein antibodies with neuropsychiatric systemic lupus erythematosus.
OBJECTIVE: Although it has been reported that anti-ribosomal P protein antibodies (anti-P) are highly specific for lupus psychosis, there have been discrepancies among the studies regarding the clinical correlation of these antibodies with systemic lupus erythematosus (SLE). The present study was therefore carried out to reappraise the association of anti-P and neuropsychiatric SLE. METHODS: Highly purified synthetic ribosomal P peptides of the carboxyl-terminal 22-amino acid sequence were conjugated to human serum albumin (HSA) with the use of glutaraldehyde. Anti-P in sera from 75 patients with SLE (26 without central nervous system disease [non-CNS], 28 with lupus psychosis, and 21 with nonpsychotic CNS involvement [nonpsychotic CNS lupus]) were analyzed with an enzyme-linked immunosorbent assay (ELISA), using HSA-ribosomal P peptide conjugates as antigens. Anti-P levels were quantitated by subtracting the nonspecific binding activities to HSA. RESULTS: The ELISA was found to be specific for anti-P, as determined by comparison with the results of Western blotting using extracts of HEp-2 cells. Serum anti-P levels were significantly elevated in patients with lupus psychosis, including organic brain syndrome and nonorganic psychosis, compared with those with non-CNS SLE or those with nonpsychotic CNS lupus. There were no significant differences in serum anti-P levels between patients with organic brain syndrome and those with nonorganic psychosis. Anti-P antibodies were not detected in the cerebrospinal fluid of patients with either lupus psychosis or nonpsychotic CNS lupus. CONCLUSION: Our results, obtained from the highly specific ELISA using HSA-ribosomal P peptide conjugates, confirm the correlation of serum anti-P with lupus psychosis. The data also suggest that differences in the purity of the ribosomal P peptides used might be a major reason for the conflicting results in the literature regarding the association of anti-P with lupus psychosis.
Antibodies, Anti-Idiotypic↗
Inhibition of human B cell activation by gold compounds.
The mechanism of action of gold compounds, which are effective in the treatment of rheumatoid arthritis (RA), has not been clearly identified. Although one of the characteristic features of RA is chronic stimulation of B cells, the effects of gold compounds on B cells have not been precisely assessed. We therefore examined the effects of gold sodium thiomalate (GST) on human B cells. IgM production was induced from highly purified B cells obtained from healthy donors by stimulation with Staphylococcus aureus Cowan 1 (SA) plus IL-2. T cell proliferation and IFN-gamma production were induced from highly purified T cells by stimulation with immobilized mAb to CD3. As little as 0.1 microg/ml (0.25 microM) GST almost completely suppressed B cell IgM production, whereas it did not suppress T cell proliferation or IFN-gamma production. The inhibition of IgM production by GST is not due to its thiomalate, but is most likely due to its gold components, since thiomalate alone did not inhibit IgM production. GST was required at the initiation of cultures to exert optimal suppressive effects on IgM production. Moreover, GST suppressed the expression of IL-2R (CD25) and transferrin receptor (CD71) on SA-stimulated B cells. These results indicate that GST preferentially inhibits the function of B cells at concentrations much lower than those which inhibit the function of T cells by interfering with the initial activation of B cells. The direct inhibitory effects of GST on human B cell activation described here may contribute at least in part to its therapeutic effect in RA.
Arthritis, Rheumatoid↗
Tenascin expression in endomyocardial biopsy specimens in patients with dilated cardiomyopathy: distribution along margin of fibrotic lesions.
OBJECTIVE: To examine the hypothesis that tenascin, an extracellular matrix glycoprotein, contributes to fibrotic changes in dilated cardiomyopathy. METHODS: The localisation of tenascin in biopsy specimens of the hearts obtained from eight patients with dilated cardiomyopathy was examined using staining by the avidin-biotin-peroxidase complex method. RESULTS: (1) Perimysium and endomysium. Although positive staining for tenascin was observed in the enlarged perimysium and endomysium in all patients, moderately intense staining was characteristically observed near the replacement fibrotic lesions. In the narrow perimysium and endomysium of the myocardium not containing replacement fibrotic lesions, tenascin was not present, as in the control specimens. (2) Replacement fibrotic lesions. Non-homogeneous positive staining for tenascin was detected in all replacement fibrotic lesions examined. Intense tenascin deposition was observed in the peripheral portion of the replacement fibrotic lesions. The tenascin staining observed in the small replacement fibrotic lesions was more intense than that in the large lesions. CONCLUSIONS: Tenascin contributes to the development of the fibrotic changes seen in the dilated cardiomyopathic heart. Its characteristic location, specifically the distribution along the margin of the fibrosis, suggests that fibrotic change is a continuous process in hearts with dilated cardiomyopathy.
Adult↗
Interaction of indometacin farnesil, a new nonsteroidal antiinflammatory drug with peripheral blood mononuclear cells from patients with rheumatoid arthritis.
Indometacin farnesil (Indo-F) is a prodrug of indomethacin designed to reduce the occurrence of side-effects by esterification of the carboxyl group on indomethacin with farnesol. We have examined the pharmacological kinetics and action of Indo-F in peripheral blood mononuclear cells (PBMNC) and polymorphonuclear leukocytes (PBPNL) from patients with rheumatoid arthritis (RA). PBMNC and PBPNL were obtained from 31 RA patients. Indo-F was incubated with PBMNC or PBPNL in the presence or absence of granulocyte-macrophage colony stimulating factor (GM-CSF) (100 pg/ml) for 3 approximately 7 days, after which the concentrations of Indo-F and indomethacin in the culture supernatants or in the cytoplasm extracts were measured with HPLC. The levels of Indo-F in the culture supernatants were significantly decreased in the presence of PBMNC or PBPNL from either normal individuals or RA patients. Indo-F was found to be taken up by PBMNC as well as by PBPNL from RA patients. Conversion of Indo-F into indomethacin was significantly enhanced by GMCSF in the presence of PBMNC, but not PBPNL. The results indicate that Indo-F is taken up by peripheral blood leukocytes from RA patients. Moreover, the data suggest that monocyte-lineage cells might play an important role in the conversion of Indo-F into indomethacin since GM-CSF markedly facilitated the conversion in the presence of PBMNC, but not PBPNL.
Adult↗
Inhibition of expression of cyclin A in human B cells by an immunosuppressant mizoribine.
Mizoribine has been used to prevent rejection of organ allografts in humans and in animal models. Recent clinical trials have demonstrated its efficacy in rheumatoid arthritis and lupus nephritis, in which abnormalities of B cell functions are also involved. We therefore examined the effects of mizoribine on the in vitro function of human B cells. IgM production was induced from highly purified B cells obtained from healthy donors by stimulation with Staphylococcus aureus Cowan I (SA) plus IL-2. Mizoribine suppressed the production of IgM at its pharmacologically attainable concentrations (1 to 3 micrograms/ml) in a dose-dependent manner. Mizoribine had to be present within the first 96 h after the initiation of cultures to exert its suppressive effects on B cell responses. Cell cycle analysis disclosed that mizoribine significantly decreased the numbers of B cells in S + G2 + M phases. Mizoribine did not decrease GTP levels in SA-stimulated B cells, whereas mizoribine led to a decrease in GTP levels in activated T cells, which was reversed by addition of GMP. Consistently, the suppressive effects of mizoribine on the IgM production of SA-stimulated B cells was not reversed by the addition of GMP as much as 40 microM, which overcame the inhibitory effects of mizoribine on the proliferation of anti-CD3-stimulated T cells. Although mizoribine did not suppress the expression of CD25 and cdc2 kinase, mizoribine markedly suppressed the expression of cyclin A in SA-activated B cells. These results indicate that mizoribine directly suppresses the function of human B cells without interfering with the initial phase of activation. Moreover, the data demonstrate that mizoribine interferes with the cell cycle progression of activated B cells by suppressing the expression of cyclin A by a mechanism distinct from guanine ribonucleotide depletion.
Adult↗
The role of IL-10 in human B cell activation, proliferation, and differentiation.
Recent studies have disclosed variable effects of IL-10 on viabilities of human B lineage cells. Thus, IL-10 has been shown to prevent apoptosis of germinal center B cells, whereas IL-10 has been found to induce apoptosis of B-chronic lymphocytic leukemia cells, suggesting the possibility that the effects of IL-10 might be different depending on the state of activation of B cells. The current studies therefore examined in detail the regulation of the survival of human peripheral blood B cells by IL-10 and its relevance to Ig production. Highly purified B cells from healthy adult individuals were cultured with Staphylococcus aureus (SA) Cowan I in the presence or absence of IL-10. When IL-10 was present during the initial activation of B cells with SA, IL-10 facilitated the apoptosis of SA-activated B cells, as determined by staining with propidium iodide, followed by analysis with flow cytometry, thus resulting in very modest IgM production. IL-2 prevented the IL-10-mediated progression of the apoptosis of SA-activated B cells during the initial activation, and thus restored the further differentiation of these B cells into Ig secreting cells. By contrast, IL-10 rather rescued SA-activated B cells from apoptosis and thus supported the differentiation of these B cells without any influences of IL-2, when it was added after 72 h of culture. Of note, cyclosporin A prevented the IL-10-mediated promotion of the apoptosis of SA-activated B cells, thus resulting in the marked enhancement of IgM production of B cells stimulated with SA + IL-10. Finally, the promotion or prevention of the IL-10-mediated apoptosis was correlated with the expression of Bcl-2 oncoprotein in SA-activated B cells. These results indicate that the effects of IL-10 are different depending on the state of activation of B cells after ligation of Ag receptors. Thus, the data have demonstrated that IL-10 during the initial activation delivers negative signals that promote the apoptosis of B cells, whereas IL-10 supports the differentiation of B cells in the complete absence of IL-2 during the subsequent responses following activation. These results therefore emphasize unique biphasic effects of IL-10 on human B cell responsiveness in determining the outcome of humoral immune responses.
Adult↗
Selective induction of IgM rheumatoid factors by CD14+ monocyte-lineage cells generated from bone marrow of patients with rheumatoid arthritis.
OBJECTIVE: To determine the capacity of CD14+ monocyte-lineage cells induced from bone marrow of rheumatoid arthritis (RA) patients to stimulate the production of IgM rheumatoid factor (IgM-RF), in order to explore the functional abnormalities of CD14+ cells and gain insight into the mechanism of selective synthesis of IgM-RF in RA. METHODS: CD14+ cells were induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation of CD14- cells purified from bone marrow cells obtained from 6 RA patients and 6 osteoarthritis (OA) patients. The production of IgM and IgM-RF was induced by stimulating B cells from normal healthy individuals with immobilized anti-CD3-activated autologous CD4+ T cells. The effects of CD14+ cells on the proportion of IgM-RF to total IgM produced by the normal B cells were assessed. RESULTS: CD14+ cells induced by GM-CSF stimulation of bone marrow CD14- cells from the 6 RA patients significantly enhanced the proportion of IgM-RF to total IgM produced by anti-CD3-activated CD4+ T cell-stimulated normal B cells (P < 0.05), whereas GM-CSF-induced CD14+ cells from the bone marrow of the 6 OA patients did not significantly affect IgM-RF production. CD14+ cells induced by GM-CSF obtained from different sites in the same RA patient on different occasions consistently enhanced the proportion of IgM-RF to IgM produced by B cells from different normal subjects. CONCLUSION: These results indicate that abnormal CD14+ monocytes stimulate RF-producing B cells to be ready to be activated by the signals delivered through noncognate T-B interactions with anti-CD3-activated T helper cells. Moreover, the data suggest that the accelerated generation of such functionally abnormal CD14+ cells from bone marrow precursors might play an important role in the pathogenesis of RA.
Aged↗
Polymorphonuclear neutrophils enhance suppressive activities of anti-CD3-induced CD4+ suppressor T cells.
We investigated the effects of polymorphonuclear neutrophils (PMN) on the suppressive activities of CD4+ suppressor T cells induced by immobilized mAb to the CD3 molecular complex in order to explore the role of PMN in the regulation of humoral immune responses. CD4+ T cells that had been treated with mitomycin C induced the IgM production from highly purified B cells in cultures stimulated with immobilized anti-CD3. Addition of CD4+ T cells that had not been treated with mitomycin C (control T4 cells) suppressed the IgM production induced by immobilized anti-CD3-stimulated T4 mito. PMN enhanced the degree of suppression of the IgM production by anti-CD3-stimulated control T4 cells. The capacity of PMN to enhance the suppressive activity of anti-CD3-stimulated control T4 cells was restored when PMN were fixed with paraformaldehyde (PFA), suggesting that direct interactions between PMN and CD4+ T cells, but not soluble factors secreted by PMN, were involved in the enhancement of suppression. Fresh PMN as well as PFA-fixed PMN enhanced the endogenous IL-2 production by immobilized anti-CD3-stimulated CD4+ T cells. Moreover, neither fresh PMN nor PFA-fixed PMN significantly augmented the suppressive activity of anti-CD3-stimulated control T4 cells in the presence of exogenous IL-2. These results indicate that PMN enhance the suppressive activity of anti-CD3-stimulated control T4 cells through direct interactions between PMN and CD4+ T cells. The enhancement of the suppressive activity of CD4+ suppressor T cells by PMN is accounted for by the enhancement of the endogenous IL-2 production by anti-CD3-stimulated CD4+ T cells. Thus, the data demonstrate that PMN influence the magnitude of humoral immune responses by regulating the production of IL-2 through direct interactions with T cells.
Adult↗
Quantitative analysis of the gastric ulcer healing process using video endoscopic pseudocolor imaging systems.
We developed an endoscopic pseudocolor imaging system in cooperation with Olympus Optical. This system was used for color processing of ulcer images observed over time using an electronic endoscope with measurement capability. The patients were receiving ranitidine (group R) or lansoprazole (group L) for ulcer treatment. By this method it is possible to differentiate between the types of healing tissue by their color. The total area of regions with a high degree of redness in the pseudocolor processed images was measured with a digitizer, and the hemoglobin-rich area (HA) in the regenerated epithelium was determined for the two groups. In the second week of drug administration, the HA was significantly larger in group L, at 170.70 +/- 64.70 mm2, than in group R, at 22.61 +/- 5.72 mm2 (p < 0.05). The hemoglobin rate was significantly higher in group L, at 0.90 +/- 0.02 (p < 0.01) at 2 weeks and 0.94 +/- 0.02 (p < 0.05) at 4 weeks, than in group R, at 0.72 +/- 0.06 and 0.86 +/- 0.05 at 2 and 4 weeks, respectively.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Familial systemic lupus erythematosus: analysis of extended haplotypes of major histocompatibility complex antigens.
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Adult↗
Reperfusion hastens appearance and extent of distribution of type I collagen in infarct zone: immunohistochemical study in rat experimental infarction.
BACKGROUND: The effects of reperfusion on time-dependent alteration of type I collagen have not been examined. OBJECTIVES: We compared the sequential changes in the appearance and distribution of type I collagen in reperfused infarct rat hearts to those in non-reperfused hearts. METHODS: Using an experimental rat model of infarction, we performed immunohistochemical staining with a polyclonal antibody to type I collagen by the avidin-biotin-peroxidase method. Reperfusion was established after 2-h coronary ligation that produced complete necrosis of myocytes. RESULTS: In reperfused hearts, type I collagen appeared in the peripheral zone of the infarct at day 2, which was 1 day earlier than in non-reperfused hearts. The extent of distribution of type I collagen in reperfused hearts was comparable to that observed approximately 1 day later in non-reperfused hearts. CONCLUSION: Reperfusion can accelerate collagen matrix formation compared with that in non-reperfused hearts after acute myocardial infarction.
Animals↗
Suppression of cytokine production of human memory T cells by roxithromycin.
Recent reports have suggested that erythromycin (EM) might have immunomodulatory activities. Roxithromycin (Rox) is a new macrolide, which has more favorable pharmacokinetic properties than EM. The current studies therefore examined the effects of Rox on the in vitro function of human T cells. Interferon-gamma (IFN-gamma) production was induced from highly purified T cells and CD45RA (-) T cell subsets from normal individuals by stimulation with immobilized anti-CD3. Rox at its pharmacologically attainable concentrations suppressed the IFN-gamma production of CD45RA (-) T cells stimulated with immobilized anti-CD3, but not that of unfractionated T cells. EM also preferentially suppressed the IFN-gamma production of CD45RA (-) T cells, but less effectively than Rox. Rox also preferentially suppressed the IL-2 production of immobilized anti-CD3 stimulated CD45RA (-) T cells. These results suggest that Rox may preferentially suppress the IFN-gamma production of memory T cells, but not that of naive T cells. Moreover, the data call for considering Rox as a possible immunomodulator for the treatment of various autoimmune disorders in which the abnormal function of CD45RA (-) T cells is involved, especially Behcet's disease.
Adjuvants, Immunologic↗
Interactions between lymphocytes and type A synoviocytes in rheumatoid synovium.
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Adult↗
Association of anti-Sm antibodies with organic brain syndrome secondary to systemic lupus erythematosus.
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Autoantibodies↗