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Akio Koyama

Publications and source records attributed to Akio Koyama.

66 records · Page 4Linked to original sources
PubMed2002

T cell receptor repertoire of T cells in the kidneys of patients with lupus nephritis.

OBJECTIVE: To determine the role of T cells in the pathogenesis of lupus nephritis (LN). METHODS: Renal biopsy specimens from 12 patients with systemic lupus erythematosus were used for the experiments. We analyzed T cell receptor (TCR) Vbeta1-20 family genes on intrarenal T cells and on peripheral blood lymphocytes (PBLs) by nested reverse transcriptase-polymerase chain reaction (PCR) and Southern blot analysis. Nucleotide sequence was determined in the third complementarity-determining region of the TCR Vbeta gene in expanded T cells. Messenger RNA (mRNA) expression levels of Th1 and Th2 cytokines on infiltrating T cells were measured by nested PCR. RESULTS: The repertoire of TCR Vbeta in intrarenal T cells was relatively restricted compared with that in PBLs. The TCR Vbeta8 and TCR Vbeta20 genes were preferentially expressed in 6 of 12 patients (50%) and the TCR Vbeta9 and TCR Vbeta14 genes were expressed in 5 of 12 patients (42%). Junctional sequences of complementary DNA encoding the TCR Vbeta8 and TCR Vbeta20 genes in intrarenal T cells showed oligoclonal expansion, indicating antigen-driven stimulation. Interleukin-4 (IL-4) and IL-10 mRNA were highly expressed on intrarenal T cells, while interferon-gamma mRNA was not detected. CONCLUSION: Our findings suggest that T cells infiltrating the kidneys of patients with LN may recognize restricted epitopes on antigens and function as Th2-type T cells.

Adolescent↗
PubMed2002

In vivo temporal EPR imaging for estimating the kinetics of a nitroxide radical in the renal parenchyma and pelvis in rats.

The kinetics of a nitroxide radical in the renal parenchyma and pelvis in rats were investigated by employing an in vivo EPR imaging system equipped with a surface-coil-type resonator (SCR). The exposed kidney of a living rat was inserted into the single-turn coil of the SCR, with the renal major axis aligned with the direction of alternative magnetic field (B(1)). After the injection of nitroxide radical via the tail vein, EPR measurements were repeated. From the temporal EPR images of the kidney on the 2-D projection to the plane which is perpendicular to the direction of B(1,) the decay rate of nitroxide radical in the renal parenchyma and pelvis was estimated. The parenchymal decay rate was found to be significantly shorter than that for the pelvis.

Animals↗
PubMed2002

Reduced serum hydroxyl radical scavenging activity in erythropoietin therapy resistant renal anemia.

Relation between anemia resistant to recombinant human erythropoietin (rHuEPO) therapy and the oxidative stress in hemodialysis (HD) patients was investigated. Stable HD patients who had consistent hemoglobin concentrations on a constant dose of rHuEPO were studied. Patients were excluded if there were factors that might affect hemopoiesis or administration of antioxidant supplements. Patients were classified into three groups: High (9000 U/week), Low (1500-4500 U/week) and No rHuEPO group. Thiobarbituric acid reactive substances (TBARS) of sera and erythrocyte were examined. Serum superoxide and hydroxyl radical scavenging activities were measured using electron spin resonance. TBARS in the erythrocyte was higher in High rHuEPO group compared with No rHuEPO group, though the serum TBARS were similar. A diminution of serum hydroxyl radical scavenging activity was observed in High rHuEPO group. Hydroxyl radical signal intensity showed a strong correlation with the serum ferritin in High rHuEPO group, although ferritin concentrations were not different among the 3 groups. Superoxide scavenging activity showed no differences. These results indicate that increased lipid peroxidation in erythrocyte, raised by decreased serum hydroxyl radical scavenging activity, is one cause of rHuEPO resistant anemia. Serum ferritin may be involved in this hydroxyl radical production.

Aged↗
PubMed2002

Mitochondrial DNA mutations in focal segmental glomerulosclerosis lesions.

Glomerular epithelial cells are primary pathogenic sites in focal segmental glomerulosclerosis (FGS) lesions. Glomerular epithelial cells are regarded as terminally differentiated cells that do not proliferate. These characteristics are also noted for neurons and muscular cells, which are major sites of mitochondrial DNA (mtDNA) mutation accumulation. Screening for mtDNA mutations was performed with renal biopsy specimens from patients with primary FGS and patients with IgA nephropathy (as subjects with secondary FGS and as control subjects). mtDNA extracted from kidney biopsy specimens was amplified with appropriate primer pairs for study of the mtDNA point mutations 3243A-->G, 3271T-->C, 8344A-->G, and 8993T-->G/C, as well as the common deletion (a 4977-bp deletion spanning mtDNA nucleotide pairs 8469 to 13447). In situ amplification of both total mtDNA and the common deletion was also performed. Two patients with FGS demonstrated the 3243A-->G point mutation; 12 patients with FGS and seven patients with IgA nephropathy accompanied by glomerulosclerotic lesions exhibited the common deletion in their kidney tissue. No patient demonstrated the mtDNA mutations 3271T-->C, 8344A-->G, or 8993T-->G/C. The degree of heteroplasmy for the 3243A-->G point mutation was >85%; however, the heteroplasmy for the common deletion was <1%. As determined with in situ PCR, normal mtDNA was mainly distributed in the tubular epithelium and mtDNA with the common deletion was mainly distributed among glomerular epithelial cells. In conclusion, it is suggested that mtDNA mutations are distributed in glomerular epithelial cells among some patients with primary FGS or secondary FGS with IgA nephropathy. These mutations may be related to glomerular epithelial cell damage.

Adolescent↗
PubMed2002

Prognosis of asymptomatic hematuria and/or proteinuria in men. High prevalence of IgA nephropathy among proteinuric patients found in mass screening.

AIM: To elucidate prognosis and prevalence of chronic renal diseases among proteinuric and/or hematuric subjects found in mass screening, a long-term follow-up study (6.35 years, range 1.03-14.6 years) was conducted on Japanese working men. METHODS: A total of 772 subjects selected from 50,501 Japanese men aged 15-62 years were found to have asymptomatic hematuria (n = 404), concomitant hematuria and proteinuria (n = 155), and proteinuria (n = 213) during their annual urine examination and five consecutive urinalyses. RESULTS: Hematuria patients showed significant improvements in urinary abnormalities as compared with both hematuria/proteinuria and proteinuria patients. Both hematuria/proteinuria patients with normotension and hematuria/proteinuria patients aged under 40 years showed significant improvements. During the follow-up period, 9.5% of the hematuria patients became hematuric/proteinuric. Hematuria/proteinuria patients had the highest risk of developing renal insufficiency. The presence of hypertension at detection of urinary abnormalities did not affect the renal function; however, if proteinuria appeared after the age of 40 years, these patients had a higher risk of developing renal insufficiency. The incidence of IgA nephropathy in the present subjects was as high as 143 cases per 1 million per year. CONCLUSION: Detailed follow-up and definitive diagnosis of asymptomatic urinary abnormalities may raise the prevalence of IgA nephropathy worldwide.

Adolescent↗
PubMed2002

Predominance of type-2 immune response in idiopathic membranous nephropathy. Cytoplasmic cytokine analysis.

BACKGROUND: The Th1/Th2 paradigm is proving increasingly useful in the understanding of infectious diseases and many autoimmune diseases. Th1 cells predominantly produce interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) and are instrumental in initiating delayed-type hypersensitivity and activating macrophages. Th2 cells secrete other cytokines, such as IL-4, IL-5, IL-10 and IL-13 that trigger B-cell activation and immunoglobulin synthesis. It has been shown that in patients with membranous nephropathy, there may be a predominance of Th2, because of the presence of IgG, particularly IgG4, which belongs to a subclass of the type-2 immune response, and complement deposits in glomeruli. In this study, we investigated the immunoresponse of helper T cells, i.e. Th predominance in patients with idiopathic membranous nephropathy. METHODS: We used flow cytometry to assess the levels of circulating Th cells in patients with idiopathic membranous nephropathy (n = 8) and in normal individuals (n = 23) based on the expression of intracellular type-1 and type-2 cytokines. Because the production of each of these cytokines has a specific time course, we observed the cytokine synthesis at 3, 6, 9 and 12 h after stimulation. RESULTS: The percentages of IL-2+/CD4+ cells from patients with idiopathic membranous nephropathy were significantly lower than those from normal individuals at 6, 9 and 12 h, with the difference becoming more significant over time. IFN-gamma+/CD4+ cells and IL-4+/CD4+ cells were not significantly different between the two groups. In patients with idiopathic membranous nephropathy, the percentages of IL-10+/CD4+ cells were significantly higher than those in normal individuals at each point in time. CONCLUSION: Increased IL-10-producing Th cells may lead to suppression of delayed-type hypersensitivity and activate suppressor cells and IgG4 synthesis, resulting in idiopathic membranous nephropathy.

Adult↗
PubMed2002

Usage of T cell receptor variable segments of the beta-chain in IgA nephropathy.

BACKGROUND: We previously reported that glomerulonephritis associated with Staphylococcus aureus infection (SAGN) showed an increased usage of T cell receptor Vbeta 5.3 and 8 in peripheral lymphocytes and mesangial IgA and IgG depositions. To elucidate the immunological mechanisms and pathogenesis of IgA nephropathy, we analyzed the usage of TCR Vbeta in both peripheral blood lymphocytes (PBLs) and renal infiltrating T cells from IgA-N patients. METHODS: In 38 patients with IgA nephropathy and controls, the usage of TCR Vbeta in PBLs were analyzed using monoclonal antibodies against Vbeta 3.1, Vbeta 5.1, Vbeta 5.2 + 5.3, Vbeta 5.3, Vbeta 6.7, Vbeta 8, Vbeta 12.1, and Vbeta 13.1 + 13.3 with three-color flow cytometry. Furthermore, we examined immunohistochemically renal biopsy specimens using antibodies against Vbeta 5.3 and Vbeta 8. RESULTS: The percentages of DR+CD4+CD8- cells, CD45RO+CD4+ cells, and CD45RO+CD4+DR+ cells in PBLs from IgA nephropathy were significantly higher than controls. The percentages of TCR Vbeta 5.3 positive cells and TCR Vbeta 8 positive cells in PBLs from patients were 1.3 +/- 0.1 and 3.1 +/- 0.2%, and both were significantly higher than controls. The percentage of renal interstitial TCR Vbeta 5.3 expression was significantly higher than that in PBLs. However, there was no significant difference between the TCR Vbeta 8 expression in the interstitium and that in PBLs. CONCLUSIONS: TCR Vbeta 5.3 and 8 usage and broad CD4+ T cell activation have occurred in IgA nephropathy. These changes were similar but weak compared with formerly reported SAGN.

Adolescent↗
PubMedDate not supplied

Staphylococcus aureus antigens induce IgA-type glomerulonephritis in Balb/c mice.

BACKGROUND: Staphylococcus aureus (S. aureus) is a common, normal pathogenic flora that colonizes mucosal tissues. We previously reported that glomerulonephritis occurs during methicillin-resistant S. aureus infection, and demonstrated polyclonal elevation of serum immunoglobulin A (IgA) and IgG levels and various histological findings, such as mesangial extracapillary and endocapillary proliferation. To investigate the pathogenic roles of S. aureus antigens, we induced IgA-type glomerulonephritis in mice by immunization with antigens derived from S. aureus, as a model of human IgA nephropathy (IgAN). METHODS: Balb/c mice (Th2 dominant type) and C57BL/6 mice (Th1 dominant type) were immunized biweekly for 4 months with antigens derived from S. aureus mixed with Freund's incomplete adjuvant. RESULTS: Mesangial proliferative glomerulonephritis with IgA, IgG and complement 3 (C3) depositions were observed in all Balb/c mice. Although C3 depositions and cell proliferation in the mesangial area were also seen in C57BL/6 mice, they were not correlated with urinary findings. In Balb/c mice, S. aureus antigens were detected in glomeruli using affinity-purified human anti-S. aureus antibodies, but there was no staining in C57BL/6 mice. The antibodies reacted with several S. aureus antigens, based on Western blot analysis, and the main 30-35 kDa band differed in intensity in Balb/c and C57BL/6 mice. In addition, increased transforming growth factor beta (TGF-beta) messenger RNA (mRNA) expression was seen in Balb/c mice compared to C57BL/6 mice. CONCLUSIONS: S. aureus antigens including, in particular, a 30-35 kDa protein and the host genetic background could play important roles in IgA-like glomerulonephritis pathogenesis.

Analysis of Variance↗
PubMedDate not supplied

Staphylococcal cell membrane antigen, a possible antigen in post-methicillin resistant Staphylococcus aureus (MRSA) infection nephritis and IgA nephropathy, exhibits high immunogenic activity that is enhanced by superantigen.

BACKGROUND: The post-methicillin resistant Staphlylococcus aureus (MRSA) infection nephritis is a progressive glomerulonephritis that occurs following Staphylococcus aureus infection. It has been assumed that staphylococcal superantigens and other cellular antigens are necessary for the development of post-MRSA infection nephritis, and we have previously identified a staphylococcal cell membrane antigen (GenBank, accession number; BAB41819.1) as a possible antigen in post-MRSA infection nephritis. In this study, we assessed the immunogenic activity of the staphylococcal cell membrane antigen and determined the relationship between the cell membrane antigen and superantigen. METHODS: Balb/c mice were immunized with glutathione S-transferase (GST) or staphylococcal cell membrane antigen-GST fusion protein. One week later, their lymphocytes were cultured with or without toxic shock syndrome toxic-1 (TSST-1) for one week. Immunoglobulin levels in the culture supernatants were measured by ELISA, and transcript expressions for cytokines, and the T-cell receptors (TCR) Vbeta17 (activated by TSST-1), Vbeta1 and Vbeta8 (not activated by TSST-1) in the culture were analyzed by reverse transcriptase polymerase chain reaction. RESULTS: Neither IgG nor IgA were detected in the culture supernatant of GST-primed lymphocytes, with or without TSST-1. In contrast, IgG and IgA levels gradually increased in direct proportion to the TSST-1 concentration in the supernatants of staphylococcal cell membrane antigen-GST fusion protein-primed lymphocytes. Various cytokine messenger RNA (mRNA) transcripts were detected in both GST-primed and staphylococcal cell membrane antigen-GST-primed cells in the presence of TSST-1. A Vbeta17 transcript could not be detected during the early culture phase under both culture conditions, while Vbeta1 and Vbeta8 T-cells survived for 7 days in the staphylococcal cell membrane antigen-GST fusion protein-primed culture in the presence of TSST-1. CONCLUSION: These results suggest that staphylococcal cell membrane antigen-GST-primed T-cells were stimulated more than GST-primed cells. Their activity was enhanced further in the presence of cytokines, which were induced by TSST-1, such that the T-cells were able to survive and activate B-cells to produce immunoglobulins.

Animals↗
PubMedDate not supplied

Post-MRSA infection glomerulonephritis with marked Staphylococcus aureus cell envelope antigen deposition in glomeruli.

A 48-year-old male developed massive proteinuria and renal dysfunction after pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) infection. Examination of a renal biopsy specimen by light microscopy showed severe mesangiocapillary proliferative glomerulonephritis with fibrocellular crescents. Immunofluorescence microscopy showed weak linear staining for immunoglobulin G (IgG), while both the peripheral and mesangial lesions stained for IgA and C3. Immunostaining for a possible antigen related to post-MRSA infection glomerulonephritis, using monoclonal antibody S1D6, revealed marked deposition of S.aureus cell envelope antigen in the glomeruli. Electron-dense deposits were observed in both the subendothelial and the mesangial areas. Focal subendothelial widening accompanied with monocytes or foam cell infiltration was also seen. The findings reflect a typical post-MRSA infection glomerulonephritis caused by S.aureus cell envelope antigen.

Antigens, Bacterial↗