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Biomedical subjects

Masanobu Miyazaki

Publications and source records attributed to Masanobu Miyazaki.

At least 19 recordsLinked to original sources
PubMed2006

Deoxyspergualin, an immunosuppressant, in patients suffering from nephropathies with crescent formation: an open-label trial to evaluate safety and efficacy.

BACKGROUND: Crescent formation in glomeruli means an acute active lesion that develops a rapidly progressive course. Therapies using pulse methylprednisolone, oral corticosteroids, and cyclophosphamide are recommended, but no agreement has been reached on the optimal therapy. There have been no controlled trials, because of the severity of this condition and because withholding treatment would become an ethical issue. METHODS: We evaluated the safety and efficacy of deoxyspergualin (DSG), an immunosuppressant, in a multicenter, prospective trial of 44 patients with crescent formation in over 10% of glomeruli, who were randomly placed into groups that received daily doses of 0.1 mg/kg (n = 21) and 0.2 mg/kg (n = 23) of DSG, given by a 1-h infusion for 4 weeks, and who were then monitored for 3 months. All patients received DSG in this open-label prospective study. We evaluated the levels of urinary protein and hematuria, and examined renal function after the DSG treatment. RESULTS: Urinary protein significantly decreased with each dose after starting the DSG administration and this efficacy was sustained for 2 months after the discontinuation of DSG. In the groups receiving 0.1 mg/kg and 0.2 mg/kg, mean urinary protein levels were 2.1 g/day and 2.3 g/day at the initiation of the DSG administration, 1.4 g/day and 1.6 g/day at week 4, and 1.5 g/day and 1.3 g/day at week 12, respectively. Hematuria was markedly improved by a dose of 0.2 mg/kg and was not exacerbated following the termination of DSG. Exacerbation of renal dysfunction, as measured by creatinine clearance, serum creatinine, and blood urea nitrogen was prevented by both doses of DSG. The most common adverse reaction was reversible neutropenia. CONCLUSIONS: Short-term treatment with DSG may be effective and tolerated in patients suffering from nephropathies with crescent formation.

Creatinine↗
PubMed2006

Renal circulatory effects of acetazolamide in patients with essential hypertension.

BACKGROUND: Reports indicate that acetazolamide (ACZ) induces the vasodilation of all vessels in animal models, as well as in small and medium kidney vessels in animal models. However, the effect of ACZ on the renal circulation of patients with essential hypertension remains unknown. In this study we examined the effects of a carbonic anhydrase inhibitor, acetazolamide (ACZ), on the renal circulation of patients with essential hypertension. METHODS: We directly infused 1000 mg of ACZ into the main renal arteries of 10 patients with essential hypertension who had undergone cardiac catheterization. We then evaluated the effects of ACZ upon heart rate, renal artery blood pressure (BP), renal artery cross-sectional area, renal Doppler blood flow velocity, renal blood flow (RBF), and renal vascular resistance (RVR). RESULTS: The infusion of ACZ was not associated with any significant changes in heart rate or in systolic or diastolic BP. However, the velocity-time integral was increased by 11.1% +/- 7.2%, from 17.6 +/- 1.8 to 20.0 +/- 3.7 cm (P = .009); RBF was increased by 39% +/- 21%, from 300 +/- 43 to 422 +/- 96 mL/min/m(2) (P = .002); and RVR was reduced by 38% +/- 20% from 24,351 +/- 2,291 to 17,651 +/- 2,731 dynes.sec.cm(-5) (P < .01). In contrast the cross-sectional area of the renal artery did not change. CONCLUSIONS: The results of the present study demonstrated that ACZ has a potent vasodilatory effect on the renal circulation of patients with essential hypertension, leading to an obvious decrease in RVR and an increase in RBF.

Acetazolamide↗
PubMed2005

Role of atrophic changes in proximal tubular cells in the peritubular deposition of type IV collagen in a rat renal ablation model.

BACKGROUND: Tubular atrophy, dilation and interstitial fibrosis are common in tubulointerstitial lesions, but the precise roles and inter-relationships of these components in the development of interstitial lesions have not been determined. This study focused on the origin and roles of atrophic tubules in the peritubular deposition of type IV collagen in a rat renal ablation model. METHODS: Male Wistar rats underwent 5/6 nephrectomy or sham operation, and then were sacrificed at 4, 8 or 12 weeks, their remaining kidneys removed for histological and immuno-histochemical studies as well as in situ hybridization for type IV collagen mRNA. RESULTS: Immuno-histochemistry demonstrated the positive staining of atrophic tubules to vimentin, platelet-derived growth factor-B chain (PDGF) and heat shock protein 47 (HSP47). Cells positive to one or more of PDGF receptor beta, alpha-smooth muscle actin (alpha-SMA), and HSP47 accumulated around atrophic tubules. Type IV collagen was also increased in the proximity of the atrophic tubules. These intimate relationships were more clearly demonstrated in 'mosaic tubules', which are composed of both intact and atrophic proximal tubular epithelial cells, and which had a mixed pattern of staining with vimentin, PDGF and HSP47. The interstitial cells positive to alpha-SMA or HSP47, or both, were in close contact with atrophic but not with intact epithelial cells. Type IV collagen was exclusively deposited between atrophic tubules and HSP47-positive interstitial cells. In situ hybridization of type IV collagen mRNA demonstrated predominant expression in atrophic tubular epithelial cells, but not in surrounding interstitial cells. CONCLUSIONS: These findings suggest that atrophic proximal tubular cells are active in the development of collagen deposition in the peritubular space, i.e. in this model type IV collagen in the interstitial fibrotic area may be produced mainly by atrophic proximal tubules.

Actins↗
PubMed2005

Role of cyclophilin B in activation of interferon regulatory factor-3.

IRF-3 is a member of the interferon regulatory factors (IRFs) and plays a principal role in the induction of interferon-beta (IFN-beta) by virus infection. Virus infection results in the phosphorylation of IRF-3 by IkappaB kinase epsilon and TANK-binding kinase 1, leading to its dimerization and association with the coactivators CREB-binding protein/p300. The IRF-3 holocomplex translocates to the nucleus, where it induces IFN-beta. In the present study, we examined the molecular mechanism of IRF-3 activation. Using bacterial two-hybrid screening, we isolated molecules that interact with IRF-3. One of these was cyclophilin B, a member of the immunophilins with a cis-trans peptidyl-prolyl isomerase activity. A GST pull-down assay suggested that one of the autoinhibition domains of IRF-3 and the peptidyl-prolyl isomerase domain of cyclophilin B are required for the binding. A knockdown of cyclophilin B expression by RNA interference resulted in the suppression of virus-induced IRF-3 phosphorylation, leading to the inhibition of the subsequent dimerization, association with CREB-binding protein, binding to the target DNA element, and induction of IFN-beta. These findings indicate that cyclophilin B plays a critical role in IRF-3 activation.

Amino Acid Sequence↗
PubMed2005

Tissue-specific expression of renin-angiotensin system components in IgA nephropathy.

BACKGROUND: The renin-angiotensin II system (RAS) has been implicated in the development of glomerulonephritis. The aims of this study were to determine (1) the expression of RAS components, angiotensin (Ang II)-forming enzymes [angiotensin-I-converting enzyme (ACE) and chymase], and Ang II receptors, and (2) the correlation between RAS expression and severity of tissue injury in IgA nephropathy (IgAN). METHODS: The expression levels of ACE, chymase, and Ang II type 1 and type 2 receptor (AT1R and AT2R) mRNAs were determined by in situ hybridization in renal specimens from 18 patients with IgAN, 5 patients with non-IgA mesangial proliferative glomerulonephritis (non-IgAN) and 10 patients with nonmesangial proliferative glomerulonephritis (minimal change nephrotic syndrome, n = 5, and membranous nephropathy, n = 5). Normal portions of surgically resected kidney served as control. RESULTS: In normal kidney, a few mesangial cells and glomerular and tubular epithelial cells weakly expressed ACE, chymase and AT1R mRNAs. In IgAN and non-IgAN samples, ACE, chymase, AT1R and AT2R mRNAs were expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells and cells of Bowman's capsule. The glomerular expressions in IgAN were stronger than in minimal change nephrotic syndrome and membranous nephropathy. In IgAN, the expressions in glomeruli correlated with the degree of mesangial hypercellularity, whereas the expression levels were weaker at the area of mesangial expansion. IgAN with severe tubulointerstitial injury showed expression of ACE, chymase, AT1R and AT2R mRNAs in atrophic tubules and infiltrating cells and such expression correlated with the degree of tubulointerstitial damage. CONCLUSION: Our results suggest that renal cells can produce RAS components and that locally synthesized Ang II may be involved in tissue injury in IgAN through Ang II receptors in the kidney.

Adult↗
PubMed2005

Nephronophthisis in two siblings.

We describe here two sisters with nephronophthisis, which was not detected until the development of endstage renal failure. Twenty- and 15-year-old female siblings were admitted to our hospital for further examination of renal dysfunction. No urinalysis abnormalities had been found in yearly health checks in either patient. The serum creatinine level was 7.2 mg/dl in case 1 (the 20-year-old) and 6.4 mg/dl in case 2. Medical history, physical findings, and laboratory tests showed no evidence of urinary tract infection, use of any drugs, arthritis, or skin eruptions. To identify the cause of the renal failure, open left renal biopsies were performed in both patients. Histopathological findings were very similar in the two patients and included marked tubular and interstitial changes (tubular dilatation, focal tubular atrophy, interstitial fibrosis, and infiltration of mononuclear cells). The glomeruli were devoid of mesangial proliferation, mesangial expansion, and adhesion of Bowman's capsule. Based on the clinical and pathological findings, the final diagnosis was nephronophthisis in both patients. It is important to remember that some progressive renal diseases, including nephronophthisis, cannot be detected even by annual urinary screening tests, which are widely performed in Japan.

Adolescent↗
PubMed2005

The role of peritoneal fibrosis in encapsulating peritoneal sclerosis.

Encapsulating peritoneal sclerosis (EPS) is a serious complication of long-term continuous peritoneal dialysis therapy. The progression of EPS has been classified into four stages by Kawanishi and colleagues: pre-EPS, and the inflammatory, encapsulating, and ileus stages. The key issue is how to diagnose EPS early enough to allow for curative treatment. In this article, we review the mechanisms of peritoneal fibrosis, especially from the perspective of collagen synthesis, and the potential role of that fibrosis in the pathogenesis of EPS.

Fibrosis↗
PubMed2005

Recommendations on the management of encapsulating peritoneal sclerosis in Japan, 2005: diagnosis, predictive markers, treatment, and preventive measures.

This comprehensive update on the management of encapsulating peritoneal sclerosis incorporates insights gained from recently published findings and the accumulated experience of the authors. Aspects covered include diagnosis, risk factors and predictive markers, treatment, and prevention, including criteria for withdrawal from peritoneal dialysis.

Biomarkers↗
PubMed2005

Successful use of icodextrin in elderly patients on continuous ambulatory peritoneal dialysis.

In peritoneal dialysis (PD), a 7.5% polyglucose-containing dialysis solution (icodextrin) provides prolonged ultrafiltration as compared with glucose-based dialysis solutions. In the present study, we attempted to clarify the safety and effectiveness of icodextrin in elderly patients on continuous ambulatory peritoneal dialysis (CAPD). Clinical data and outcomes of 16 patients aged 65 or older were monitored for 12 weeks before and during icodextrin treatment. The group included 13 men and 3 women with a mean age of 69 +/- 5 years (range: 66-78 years). The underlying kidney disease was chronic nephritis in 7 patients, diabetes mellitus in 8 patients, and nephrosclerosis in I patient. From the beginning of peritoneal dialysis, 1 patients had been treated with icodextrin; the other 10 were changed to icodextrin from glucose dialysis solution. At the end of study, body weight had increased to 63.8 +/- 9.3 kg from 61.6 +/- 9.3 kg, accompanied by an increase in ultrafiltration to 480 +/- 207 mL daily from 369 +/- 436 mL daily. No significant change in urine volume occurred. Despite the increase in body weight, cardiothoracic rate decreased to 51.1% +/- 3.4% from 52.3% +/- 4.9%. All patients reported an improvement of edema and appetite. Edema scores were significantly decreased to 0.85 +/- 0.90 from 1.63 +/- 0.96 (p < 0.03). No adverse side effects were associated with the use of icodextrin. From the foregoing data, we concluded that, as compared with conventional glucose solution, icodextrin has beneficial effects on ultrafiltration volume and clinical symptoms in elderly patients on CAPD.

Aged↗
PubMed2004

Histologically confirmed superimposition of post-streptococcal acute glomerulonephritis during IgA nephropathy.

We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed "hump" electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.

Acute Disease↗
PubMed2004

Clinical and immunohistochemical study of immunoglobulin A nephropathy (IgAN) before and after tonsillectomy.

Tonsillectomy often improves clinical features in immunoglobulin A nephropathy (IgAN), however, the mechanisms mediating clinical modifications are unclear. In the present study, we examined the immunohistological alterations in biopsy specimens obtained from IgAN patients before and after tonsillectomy. We investigated eight IgAN patients who underwent repeated renal biopsy in the present study. Immunohistochemistry for alpha-smooth muscle actin (alpha-SMA), CD68 and proliferating cell nuclear antigen (PCNA) were performed and histological findings were compared before and after tonsillectomy. None of the patients were treated with steroids or immunosuppressive drugs before second renal biopsy. The expression of alpha-SMA and the number of CD68 positive cells were significantly decreased in IgAN patients with improvement of proteinuria and hematuria after tonsillectomy. The degree of mesangial cell proliferation, expansion of mesangial area and the number of PCNA positive cells were not changed after tonsillectomy. These results suggest that the reduced number of activated mesangial cells and macrophages may be involved in the improvement of hematuria after tonsillectomy. They also suggest that tonsillectomy may improve proteinuria and hematuria in some patients with IgAN through reduction of mesangial cell activation and macrophage infiltration.

Actins↗
PubMed2004

TNP-470, an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model.

BACKGROUND: In patients on long-term peritoneal dialysis (PD), angiogenesis and vasculopathy are observed in the peritoneum, and the degree of vascularization correlates with the area of fibrotic tissue, suggesting the involvement of angiogenesis in the progression of peritoneal fibrosis. The aim of the present study was to evaluate the effect of TNP-470, an anti-angiogenic compound, on the development of peritoneal fibrosis induced by chlorhexidine gluconate (CG). METHODS: Peritoneal fibrosis was induced by injection of CG into peritoneal cavity of Institute for Cancer Research (ICR) mice. TNP-470 was injected subcutaneously with CG. Mice were sacrificed, and peritoneal tissues were dissected out at days eight and 16 after CG and TNP-470 injection. The expression patterns of CD31 (as a marker of endothelial cells), vascular endothelial cell growth factor (VEGF), alpha-smooth muscle actin (as a marker of myofibroblasts), heat shock protein 47 (HSP47), type III collagen, F4/80 (as a marker of mice macrophages), proliferating cell nuclear antigen (PCNA), and cyclin-dependent kinase 2 (Cdk2) were examined by immunohistochemistry. RESULTS: CG-injected mice showed thickening of the submesothelial zone and increased number of vessels, myofibroblasts, and infiltrating macrophages. The expression levels of VEGF, type III collagen, and HSP47 were increased, and a large number of PCNA-positive cells and Cdk2-expressing cells were observed in the thickened submesothelial area. Treatment with TNP-470 suppressed the submesothelial zone thickening and reduced collagen III expression as well as angiogenesis. TNP-470 also decreased the number of VEGF-expressing cells, myofibroblasts, macrophages, PCNA-positive cells, and Cdk2-expressing cells. CONCLUSION: Our results indicate the involvement of angiogenesis in the progression of peritoneal fibrosis, and suggest that TNP-470 may be potentially useful for the prevention of peritoneal fibrosis through inhibition of angiogenesis and suppression of myofibroblast proliferation.

Actins↗