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Biomedical subjects

Y Ozono

Publications and source records attributed to Y Ozono.

At least 37 records · Page 2Linked to original sources

Anti-CD8 monoclonal antibody protects against spontaneous IgA nephropathy in ddY mice.

We investigated the effects of anti-CD4 monoclonal antibody (mAb) and/or anti-CD8 mAb in ddY mice, an animal model of spontaneous IgA nephropathy. Female ddY mice were treated with 18 intravenous injections of anti-CD4 and/or anti-CD8 mAb at 2-week intervals. This was based on our observation that a single injection of anti-CD4 mAb or anti-CD8 mAb caused a selective depletion in CD4+ T cells for 2 weeks and CD8+ T cells for 4 weeks, respectively. The level of proteinuria, serum IgA, and changes in the histopathological features of renal tissue samples were assessed in treated mice between the age of 4 and 40 weeks. The level of proteinuria increased with age, but there was not significant difference among the groups. No animal developed microhematuria throughout the study. Treatment with anti-CD4 mAb produced a mild to moderate level of mesangial hypertrophy at 20 and 40 weeks, similar to the results in untreated mice. The lowest degree of mesangial hypertrophy occurred in mice treated with anti-CD8 mAb up to the age of 40 weeks. Treatment with a combination of anti-CD4 and anti-CD8 mAbs produced effects that were similar to those observed on treatment with anti-CD8 mAb alone. Our results suggest that CD8+ T cells mediate mesangial proliferation and the progression of nephropathy in ddY mice.

Animals↗

Successful treatment with cyclosporine in a case of hemophagocytic syndrome manifesting as severe liver dysfunction.

Forms of hemophagocytic syndrome, which affects mainly children, vary from mild to very severe and often fatal. We describe an adult patient with hemophagocytic syndrome in whom severe liver dysfunction developed. The condition continued to deteriorate despite treatment with plasma exchange, high-dose gamma globulin, and corticosteroid therapy. Treatment with cyclosporine (2.3 mg/kg/day) dramatically improved the condition and normalized liver function. Cyclosporine reduced the serum levels of ferritin, interferon-tau, interleukin-6, and soluble interleukin-2 receptor. These findings suggest that hemophagocytic syndrome accompanied with severe liver dysfunction results from hypercytokinemia, and cyclosporine is useful in preventing a fatal outcome during the acute phase.

Adult↗

Plasmapheresis in the treatment of rapidly progressive glomerulonephritis.

The present study was carried out to examine the efficacy of plasma exchange in patients with rapidly progressive glomerulonephritis (RPGN). Seventeen patients with RPGN were treated with plasmapheresis as adjunct to immunosuppressive therapy. Of these, 4 had antiglomerular basement membrane (GBM) antibody-mediated glomerulonephritis (GN), 8 had immune-complex GN (5 SLE, 2 HSP, 1 cryoblobulinemia), 5 had pauci-immune GN (3 peripheral antineutrophil cytoplasmic antibody [P-ANCA], 1 cytoplasmic antineutrophil cytoplasmic antibody [C-ANCA], 1 other). Treatment of 10 of these patients with plasmapheresis within the first month of disease onset resulted in a stable renal function for a period extending from 1 to 3 years, except in 2 patients who had high baseline levels of serum creatinine. In the remaining patients, 2 were treated with hemodialysis 6 years later at the end of follow-up. We conclude that plasmapheresis, when used in combination with immunosuppressive drugs, is beneficial, leading to improved renal function.

Basement Membrane↗

[Cytomegalovirus retinitis in a patient with systemic lupus erythematosus].

We report a rare case of cytomegalovirus (CMV) retinitis in association with systemic lupus erythematosus (SLE). A 36-year-old female was admitted to our hospital because of nephrotic syndrome and renal insufficiency due to lupus nephritis. After steroid and immunosuppressant treatment for lupus nephritis, she began to complain of floaters and visual disturbance. She was diagnosed as having CMV retinitis based upon the depressed immune status and the clinical appearance of fundus. As soon as CMV retinitis was diagnosed, antiviral treatment with intravenous ganciclovir was instituted and maintained for 7 months. She was treated successfully and almost no progression or relapse of CMV retinitis was documented without ganciclovir maintenance treatment during a 2 year follow-up period. It is suggested that CMV retinitis can occur in patients with SLE treated with steroid and immunosuppressant, indicating the importance of early diagnosis and treatment for CMV retinitis.

Adult↗

Involvement of IL-4 in human glomerulonephritis: an in situ hybridization study of IL-4 mRNA and IL-4 receptor mRNA.

Interleukin-4 (IL-4) has been recently implicated in the pathogenesis of glomerulonephritis. However, the expression of IL-4 and IL-4 receptor (IL-4R) in human kidney has not been fully determined. Nonradioactive in situ hybridization was used to examine the expression of IL-4 mRNA and IL-4R mRNA in tissues from normal kidneys and specimens from a variety of human kidney diseases. In normal glomeruli, a few mesangial cells and cells of the Bowman's capsule weakly expressed IL-4 and IL-4R mRNA, whereas in diseased glomeruli both mRNA types were strongly expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells, and cells of the Bowman's capsule. The relationship between the expression of these mRNA and the degree of glomerular injury was different in different types of glomerulonephritis. In IgA nephropathy and non-IgA mesangial proliferative glomerulonephritis, IL-4 expression correlated positively with the degree of mesangial hypercellularity and extracellular matrix expansion. However, IL-4R expression was relatively constant. In contrast, the expression of IL-4 and IL-4R mRNA correlated negatively with the degree of glomerular injury in lupus nephritis. Coexpression and discordant expression of these mRNA forms were observed in individual cells. In tubulointerstitium with severe lesions, IL-4 mRNA and IL-4R mRNA were observed in atrophic tubules and some of the infiltrating cells and fibroblasts. The interstitial expression of these mRNA forms was similar in IgA nephropathy, non-IGA mesangial proliferative glomerulonephritis, and lupus nephritis and correlated positively with the degree of tubulo-interstitial changes. These results suggest that an autocrine and/or paracrine pathway of IL-4 is present in human diseased kidneys and that IL-4 may be involved in tissue injury in glomerulonephritis.

Adult↗

Intraglomerular C3 synthesis in rats with passive Heymann nephritis.

Passive Heymann nephritis (PHN), a model of human membranous nephropathy, is an immune-complex-mediated glomerulonephritis characterized by the presence of complement-dependent tissue injury. Recent studies have confirmed the synthesis of C3, involved in both the classical and alternative pathways of complement, in injured human and animal renal tissues. However, there is little clear information on the role of local C3 synthesis in the pathogenesis of nephritides such as PHN. In the present study, using nonradioactive in situ hybridization and semiquantitative reverse transcriptase polymerase chain reaction, we examined C3 synthesis in the kidney and its contribution to tissue injury in a rat model of PHN induced by the injection of polyclonal anti-gp330 antibody. C3 mRNA was localized in mesangial cells, glomerular epithelial cells, and cells of Bowman's capsule. During the early stages of PHN, C3 mRNA expression was detected in mesangial cells and glomerular epithelial cells, whereas such expression was limited to mesangial cells during the late stages of the disease. Focal, weak C3 mRNA expression was detected in tubular epithelial cells and occasionally in the interstitium. Semiquantitative polymerase chain reaction demonstrated that the level of C3 mRNA expression correlated with that of proteinuria. Our results suggest that renal cells synthesize C3 mRNA in PHN in a site-specific manner and that locally produced C3 is associated with the development of proteinuria in this model.

Animals↗

[A case of systemic lupus erythematosus associated with minimal change nephrotic syndrome].

A case of systemic lupus erythematosus (SLE) associated with minimal change nephrotic syndrome (MCNS) in a 25-year-old female is described. The patient suddenly manifested butterfly rash and proteinuria was first pointed out on March, 1994. On admission, her skin biopsy indicated SLE. Subsequently, she developed nephrotic syndrome. Urinalysis showed heavy proteinuria (4.1 g/day), with no other abnormalities in the urinary sediment. Immunological examination revealed positive antinuclear antibody at a titer of 1:80 with a speckled pattern. Anti-ssDNA and anti-SS-A antibodies were positive, but other antibodies were negative. Serum complement (CH50) was within the normal range (30.5 U/ml). The renal biopsy showed no apparent cellular proliferation or increase of extracellular matrices in glomeruli by light microscopy. Slight deposition of IgG, IgM, C3 and C1q was focally seen in the mesangium and capillary wall by immunofluorescence. Electron microscopic examination revealed small and scattered dense deposits in the mesangium, subepithelium and subendothelium, associated with diffuse fusion of the foot processes of epithelial cells along the glomerular basement membrane. According to the WHO classification, the histological features were compatible with those of lupus nephritis (LN), class Ib. The patient was treated with PREDNISOLONE, Mizorbine and Dilazep, resulting in the disappearance of proteinuria and a normal serum level of total protein. The association of LN and MCNS is very rare. We also investigated the relationship between the intensity of proteinuria and histological types of 53 cases with LN examined in our laboratory. The cases with heavy proteinuria were mostly classified as WHO-Class IV and Class V. We report here a case of LN associated with MCNS and also review the literatures.

Adult↗

Intraglomerular C3 synthesis in human kidney detected by in situ hybridization.

Complements 3 and 4 are known to be synthesized in diseased renal tissue and the mRNA of these complements has been demonstrated, using polymerase chain reaction, in renal biopsies from nephritic patients. However, the types of cells producing the complements in intact renal tissue have not been defined. To identify the renal cellular components involved in complement synthesis, we analyzed the expression of C3 mRNA in renal tissues from patients with immune-complex glomerulonephritis by a high-resolution in situ hybridization using digoxigenin-labeled oligonucleotide. Renal tissues from 15 patients with immunoglobulin (Ig) A nephropathy (IgAN), five with lupus nephritis (LN), and five with minimal change nephrotic syndrome (MCNS) were examined. Uninvolved portions of surgically removed kidney with tumors served as normal controls. C3 mRNA was detected in mesangial cells, glomerular epithelial cells, and Bowman's capsule in IgAN and LN. In the interstitium, some tubules and some infiltrating mononuclear cells were positively stained for C3 mRNA. C3 mRNA was not detected in MCNS and control tissues. Our results confirm that the glomerular resident cells can synthesize C3 in immune-mediated glomerulonephritis and suggest that locally synthesized complement may be involved in tissue injury in glomerulonephritis.

Biopsy↗

Detection of cytokine mRNA-expressing cells in peripheral blood of patients with IgA nephropathy using non-radioactive in situ hybridization.

IgA nephropathy (IgA-N) is considered to be an immune-mediated disorder and several immunological abnormalities have been observed. In the present study, we optimized non-radioactive in situ hybridization and applied this technique to evaluate the degree of expression of various cytokine mRNAs in peripheral blood mononuclear cells (PBMC) taken from patients with IgA-N on cytospin preparation. Using this method, together with image analysis, we examined the expression of mRNA in cells which secrete cytokines, such as IL-2, interferon-gamma (IFN-gamma), IL-4, IL-5 and IL-6. The expression of these mRNAs was clearly observed in monocytes and lymphocytes at a single-cell level. Compared with healthy adults, the expression of IL-4 mRNA, IL-5 mRNA and IL-6 mRNA, but not IL-2 mRNA or IFN-gamma mRNA, was significantly enhanced. Our results indicate that non-radioactive in situ hybridization method is a powerful technique for analysis of cytokine mRNAs in PBMC at a cellular level. Our results also suggest that mRNA expression of IL-4, IL-5 and IL-6, produced by Th2 cells, is increased in patients with IgA-N. The abnormal regulatory process involved in cytokine expression may play an important immunopathologic role in IgA-N.

Adult↗

Changes in circulating immune complex and charge distribution with upper respiratory tract inflammation in IgA nephropathy.

The circulating IgA class immune complex (IgA-IC) and its charge distribution, at the appearance of macroscopic hematuria and after tonsillectomy in patients with IgA nephropathy, were investigated in the present study. 3.5% polyethylene glycol precipitate (3.5% PEG-IgA) was used for IgA-IC detection and isoelectric focusing for its charge distribution. The level of IgA in 3.5% PEG-IgA, principally IgA1, and the proportion of anionic 3.5% PEG-IgA (isoelectric point, pl, 4.8-5.6) were significantly elevated in episodes of macroscopic hematuria with upper respiratory tract inflammation and with the appearance of macroscopic hematuria 1 day after tonsillectomy. Therefore, an increase in anionic IgA-IC (pl 4.8-5.6), principally IgA1, and the tonsils were considered to be concerned with the mechanism involved in the appearance of macroscopic hematuria.

Adult↗

A case of acute renal failure due to ethylene glycol intoxication.

We describe an 18-year-old man with acute renal failure due to inadvertent ingestion of antifreeze that contained ethylene glycol (EG). A relatively small amount of EG was ingested, but nausea and vomiting were observed soon after ingestion. During admission to a local hospital, consciousness became impaired and generalized convulsion was noted. He was transferred to our hospital because of rapid deterioration of renal function. Emergency hemodialysis was begun. The patient underwent one treatment session of hemodialysis each day, for a total of 8 hemodialytic sessions before his renal function recovered. Examination of the renal biopsy specimen revealed degeneration of the renal tubular epithelium and presence of intratubular calcium oxalate crystals. The clinical features of the patient were mild except for acute renal failure. These findings suggest that even a small amount of EG will have toxic effects on the kidney.

Acute Kidney Injury↗

Expression and function of fibronectin receptors on peripheral mononuclear cells in IgA nephropathy.

The beta 1 integrin family, major adhesive receptors for the extracellular matrix (ECM), have been reported to be present in normal and diseased kidneys. Attachment of glomerular cells to ECM is mediated by beta 1 integrins. Several members of the beta 1 integrins are referred to as VLA (very late activation) antigens. Peripheral mononuclear cells also express VLA antigens in both resting and activated states. We examined the expression and function of VLA antigens on peripheral lymphocytes and monocytes in patients with IgA nephropathy using monoclonal antibodies (mAbs) specific for VLA alpha-chains. Peripheral lymphocytes from patients with IgA nephropathy expressed VLA-4 alpha and 5 alpha, but not VLA-1 alpha, 2 alpha or 3 alpha. Peripheral monocytes from patients with IgA nephropathy expressed VLA-2 alpha, 4 alpha and 5 alpha, but not VLA-1 alpha or 3 alpha. The expression of VLA adhesive receptors was observed in healthy individuals. Adhesion assay to fibronectin revealed augmented adhesion of mononuclear cells in IgA nephropathy (P < 0.05), and this increased adhesion was inhibited by mAbs to VLA-4 alpha and 5 alpha. The expression of beta 1 integrins in IgA nephropathy was similar to that of healthy individuals, but the function of these molecules in terms of adhesion to fibronectin though VLA-4 and VLA-5 is increased in these patients. These findings suggest that the activation of fibronectin receptors on peripheral mononuclear cells plays an important role in the pathogenic process of IgA nephropathy.

Adolescent↗

Acute tubular necrosis with loin pain and persistent multiple wedge-shaped contrast enhancement on CT.

A 38-year-old man had severe loin pain and computed tomography performed 48 hours later, after drip infusion pyelography (DIP), revealed wedge-shaped contrast enhancement. He showed mild impairment of renal function with no evidence of rhabdomyolysis. The loin pain lasted for 5 days and the wedge-shaped contrast enhancement on CT persisted for 14 days and improved. The case was compatible with the new syndrome, loin pain and persistent wedge-shaped contrast enhancement on CT, proposed by Ishikawa et al (Nephron 27: 31, 1981).

Adult↗

Effect of tonsillectomy on peripheral blood T cell surface markers and cytokine production in patients with IgA nephropathy accompanied by chronic tonsillitis.

The present study investigated changes in peripheral blood T cell surface markers and cytokines (interleukin-2, IL-2; tumor necrosis factor-alpha, TNF-alpha; and interferon-gamma, IFN-gamma) following tonsillectomy in patients with IgA nephropathy accompanied by chronic tonsillitis. Peripheral blood CD8+ cells, CD45RA+CD4+ cells and CD8+CD11b- cells increased significantly after tonsillectomy, compared with their preoperative values. In some cases, the preoperative serum TNF-alpha and IFN-gamma levels were higher than normal before surgery, but decreased after surgery. These results suggest that tonsillectomy suppresses a decrease in suppressor T cells in patients with IgA nephropathy and corrects abnormal cell-mediated immune responses in these patients.

Adult↗